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Bibliography on: Long Covid

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 18 May 2025 at 01:50 Created: 

Long Covid

Wikipedia: Long Covid refers to a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. Long COVID is characterised by a large number of symptoms, which sometimes disappear and reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. Many other symptoms can also be present, including headaches, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction and problems with mental health. Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. Diagnosis of long COVID is based on suspected or confirmed COVID-19 infection, symptoms and by excluding alternative diagnoses. Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. Prevalence is less after vaccination.

Created with PubMed® Query: ( "long covid" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2025-05-14

Vu PD, S Abdi (2025)

Post-acute sequelae SARS-CoV-2 infection and neuropathic pain: a narrative review of the literature and future directions.

Pain management [Epub ahead of print].

PURPOSE OF REVIEW: Neuropathic pain is a recognized and debilitating symptom of SARS-CoV-2 infection across acute, post-acute, and long-COVID phases. Initially emerging as acute or subacute symptoms, these neuropathic manifestations can evolve into chronic conditions, with approximately 10% of all SARS-CoV-2 cases (estimated 65 million individuals globally) developing post-acute SARS-CoV-2 (PASC) neuropathic sequalae. Given the limited literature specifically addressing neuropathic pain related to PASC, a deeper understanding is needed to improve management and reduce patient burden.

RECENT FINDINGS: PASC symptoms are associated with disease severity, elevated body mass indexes, preexisting psychological conditions, and addiction history. Sex differences appear to influence prevalence, and the multisystem nature of PASC complicates symptom presentation, with mood disorders, fatigue, and cognitive dysfunction contributing to altered pain perception. Proposed mechanisms include immune dysregulation, persistent viral protein effects, and neuroanatomical changes. Management typically involves a multimodal approach.

SUMMARY: This review examines SARS-CoV-2 neuropathic pain across the illness trajectory, examining its pathophysiology, prevalence, and treatment. It highlights the potential for subacute neuropathic symptoms to become chronic and calls for future research to refine long-term management strategies and assess broader healthcare implications.

RevDate: 2025-05-16
CmpDate: 2025-05-14

Ortega-Martin E, J Alvarez-Galvez (2025)

Living With Long COVID: Everyday Experiences, Health Information Barriers and Patients' Quality of Life.

Health expectations : an international journal of public participation in health care and health policy, 28(3):e70290.

BACKGROUND: Long COVID has considerably impacted patients' daily lives, yet qualitative insights in Spain are still scarce. This study seeks to (1) explore patients' experiences and the barriers they face, (2) analyse challenges in accessing accurate information and (3) evaluate the effects on quality of life by examining its dimensions in detail.

METHODS: Semi-structured interviews were conducted with 23 participants in Spain with Long COVID. Thematic analysis was performed, investigating needs, obstacles in daily life, challenges in obtaining and understanding health knowledge and its effects on the quality of life.

RESULTS: The most frequent symptoms were chronic pain and postexercise fatigue. All individuals encountered restrictions in their daily lives, which often had financial consequences. A lack of recognition coupled with legal insecurity due to the absence of a formal diagnosis further compromised their economic stability. Stigmatisation and poor social understanding led to feelings of loneliness and distress, adding to the overall impact of the disease. Health fragmentation, lack of follow-up and absence of coordinated multidisciplinary treatment limited specialised treatment and health information. Therefore, many patients sought information and support from online communities. However, misinformation and information overload or contradictory information generated confusion, affecting decision-making about the management of their disease, affecting disease management and quality of life.

CONCLUSION: The impact of Long COVID transcends physical health, pointing to economic pressure, legal uncertainty and fragmentation of care. We reveal how misinformation and a lack of guidance intensify inequities in access to reliable information. These findings underscore the need for integrated models of care, policy recognition and targeted strategies to reduce socio-economic inequalities.

This study expands knowledge about the experiences of people with Long COVID in Spain. Their journeys in the healthcare system and the challenges they face are key to the analysis and findings. Patient associations supported recruitment to ensure a broad range of viewpoints.

RevDate: 2025-05-15

Sun H, Dang R, Haack M, et al (2025)

Facility-measured nocturnal hypoxemia and sleep among adults with long COVID versus age- and sex-matched healthy adults: a preliminary observational study.

Sleep advances : a journal of the Sleep Research Society, 6(2):zpaf017.

STUDY OBJECTIVES: Persistent post-acute sequelae of SARS-CoV-2 infection, i.e. long COVID, impacts multiple organ systems. While lower blood oxygen is expected when SARS-CoV-2 infects the lungs, hypoxia without pulmonary symptoms may continue after the acute phase. Ventilation and blood oxygen are more vulnerable during sleep, but nocturnal hypoxemia hasn't been studied in people with long COVID in a facility setting using gold-standard polysomnography (PSG).

METHODS: We conducted an observational study with 50 participants (25 long COVID, 25 age-sex-matched healthy controls) using in-laboratory overnight PSG. We calculated the average SpO2, average SpO2 after removing desaturations, the respiratory rate in different sleep periods, and the hypoxic costs using all desaturations.

RESULTS: We found that average SpO2 was lower in participants with long COVID: 1.0% lower after sleep onset (p = .004) and 0.7% lower during REM (p = .002); average SpO2 after removing desaturations was also lower in participants with long COVID: 1.3% lower after sleep onset (p = .002), 0.9% lower during REM (p = .0004), and 1.4% lower during NREM (p = .003); and respiratory rate was 1.4/minute higher in participants with long COVID during REM (p = .005). There were no significant differences in SpO2 and respiratory rate before sleep onset, the within-participant change from before to after sleep onset, or hypoxic costs.

CONCLUSIONS: The results suggest that long COVID had a persistent lower nocturnal blood oxygen saturation, and support the need for a large-scale study of nocturnal hypoxemia in people with long COVID compared to the general population.

RevDate: 2025-05-14

Fernández-de-Las-Peñas C, Franco-Moreno A, Ruiz-Ruigómez M, et al (2025)

Intravenous Administration of Remdesivir at the Acute Phase of SARS-CoV-2 Infection Is Associated with a Lower Prevalence of Post-COVID-19 Pain.

Journal of clinical medicine, 14(9):.

Background/Objective: Evidence suggests that the administration of antivirals at the acute phase of SARS-CoV-2 infection is associated with lower COVID-19 severity, accordingly, the administration of antivirals at the acute phase of the infection could prevent post-COVID-19 symptoms. The current study investigated the effects of the intravenous administration of Remdesivir at hospitalization (acute phase of SARS-CoV-2 infection) in COVID-19 survivors on the development of post-COVID-19 pain symptoms. Methods: A cohort of previously hospitalized COVID-19 survivors who received intravenous administration of Remdesivir at the acute COVID-19 phase (n = 216) were matched with a cohort of previously hospitalized COVID-19 survivors who did not receive any antiviral treatment at the acute phase of the infection (n = 216). In a face-to-face interview, they were asked for the development of pain symptoms attributed to SARS-CoV-2 infection and whether the symptom persisted at the time of the study (mean follow-up: 18.4, SD: 0.8 months). Clinical/hospitalization data were collected from medical records. Anxiety/depressive symptoms and sleep quality were also assessed with validated self-reported questionnaires. Results: No differences in hospitalization data and the presence of previous chronic conditions were seen between patients receiving or not receiving intravenous administration of Remdesivir during hospitalization. The multivariate analysis revealed that the intravenous administration of Remdesivir at the acute COVID-19 phase was a protective factor for the development of overall post-COVID-19 pain (OR 0.444, 95% CI 0.292-0.674, p < 0.001). A protective effect of administrating intravenous Remdesivir was specifically seen for thorax/chest (OR 0.277, 95% CI 0.100-0.766, p = 0.01) and lumbar spine (OR 0.347, 95% CI 0.143-0.844, p = 0.02) pain. Conclusions: Current results support a potential protective role of the intravenous administration of Remdesivir at the acute phase of SARS-CoV-2 infection for developing long-term post-COVID-19 pain in previously hospitalized COVID-19 survivors. Studies investigating the effects of the oral administration of antivirals in non-hospitalized populations are needed to generalize these findings.

RevDate: 2025-05-14

Brewer KD, Santo NV, Samanta A, et al (2025)

Advances in Therapeutics for Chronic Lung Diseases: From Standard Therapies to Emerging Breakthroughs.

Journal of clinical medicine, 14(9):.

Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies.

RevDate: 2025-05-14

Moustakli E, Stavros S, Michaelidis TM, et al (2025)

Long-Term Effects of COVID-19 on Women's Reproductive Health and Its Association with Autoimmune Diseases, Including Multiple Sclerosis.

Journal of clinical medicine, 14(9):.

Concern over COVID-19's long-term influence on women's reproductive health is growing, with emerging research suggesting potential links to ovarian dysfunction, menstrual irregularities, fertility challenges, and adverse pregnancy outcomes. Post-viral immune dysregulation is linked to both the development and exacerbation of autoimmune diseases, including multiple sclerosis (MS). Long COVID has been associated with immunological dysfunction, hormonal imbalances, and chronic inflammation, all of which may worsen autoimmune disorders and reproductive health issues. Long COVID is characterized by symptoms persisting for weeks or months beyond the acute infection phase. There are indications that prolonged COVID may contribute to autoimmune disease development through mechanisms such as immune hyperactivation, molecular mimicry, and dysregulated cytokine responses. Although this research field is still emerging, growing evidence suggests that SARS-CoV-2 infection may have lasting effects on women's health, highlighting the need for further studies into its underlying mechanisms and long-term clinical outcomes. This review compiles recent findings on the long-term impact of COVID-19 on women's reproductive health and its potential association with autoimmune disorders, particularly MS.

RevDate: 2025-05-15

Gentilotti E, Canziani LM, Caponcello MG, et al (2025)

ORCHESTRA Delphi consensus: diagnostic and therapeutic management of post-COVID-19 condition in vulnerable populations.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases pii:S1198-743X(25)00172-7 [Epub ahead of print].

OBJECTIVES: Post-COVID-19 condition (PCC) remains poorly understood, especially in clinically vulnerable groups. We applied the Delphi approach to drive recommendations for the diagnosis, management, and prevention of PCC in people living with HIV (PWH) and patients affected by rheumatological diseases (RD) and haematological malignancies.

METHODS: On the basis of literature review, three areas of interest in PCC in PWH, haematological malignancies, and RD were identified: (a) features and risk factors; (b) diagnosis and management; and (c) prevention. A three-round Delphi anonymous survey consisting of 15 questions was conducted including 69 experts. Consensus was measured by the six-point Likert scale categorized into four tiers: strong disagreement, moderate disagreement, moderate agreement, and strong agreement. Statements were generated on questions achieving consensus.

RESULTS: Eleven statements were generated: six on features and risk factors of PCC in clinically vulnerable populations, two on diagnosis and management, and three on prevention. Chronic fatigue was identified as the most frequent presentation of PCC in PWH and RD populations. A different case definition of PCC is required for RD population, as symptoms of PCC and autoimmune disorders may overlap. Risk factors for PCC include age >65, severity of COVID-19, and female sex; the latter is also associated with increased smell/taste impairment. A clinical assessment or a routine laboratory test performed 3 months after acute infection is not suggested to diagnose PCC in PWH. PWH and RD should be screened to exclude additional autoimmune disorders in case of chronic fatigue/arthralgia of new onset. Full-course vaccination and early treatment for COVID-19 should be promoted to prevent PCC, whereas corticosteroids during acute infection are not recommended.

DISCUSSION: Diagnosis, management, and prevention of PCC are still under discussion. This Delphi offers valuable insights on PCC in selected clinically vulnerable populations and suggests a tailored approach in vulnerable populations.

RevDate: 2025-05-14

Qiu S, Hadidchi R, Vichare A, et al (2025)

SARS-CoV-2 Infection Is Associated with an Accelerated eGFR Decline in Kidney Transplant Recipients up to Four Years Post Infection.

Diagnostics (Basel, Switzerland), 15(9): pii:diagnostics15091091.

Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2. Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan-Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time. Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased -0.98 units/year [-1.50, -0.46]. By contrast, eGFR declined at a significantly greater rate (-1.80 units/year [-2.45, -1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate. Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population.

RevDate: 2025-05-13
CmpDate: 2025-05-14

Shi J, Lu R, Tian Y, et al (2025)

Prevalence of and factors associated with long COVID among US adults: a nationwide survey.

BMC public health, 25(1):1758.

BACKGROUND: People with long COVID report prolonged, multisystem involvement and significant disability. This study aimed to determine long COVID prevalence and factors associated with it among US adults using nationally representative data.

METHODS: This cross-sectional analysis utilized data from 2022 Behavioral Risk Factor Surveillance System survey, a nationally representative telephone survey conducted among noninstitutionalized adults aged ≥ 18 years residing in the United States. Age-adjusted prevalence of long COVID was calculated using weighted survey analysis. Poisson regression was employed to assess adjusted prevalence ratios (aPRs) associated with long COVID across various demographic, socioeconomic and health-related characteristics.

RESULTS: Among 390,233 participants, 120,178 reported COVID-19, with 25,582 experiencing long COVID. Age-adjusted prevalence of self-reported COVID-19 and long COVID were estimated at 34.1% (95% CI, 33.7-34.4%) and 7.2% (95% CI, 7.0-7.4%) as of 2022, respectively. Among adults reporting COVID-19, 20.9% (95% CI, 20.5-21.4%) had ever experienced long COVID. An inverted U-shaped association was observed between long COVID risk and age, with the highest prevalence (23.5%) in the 45-54 age group. Long COVID was more prevalent among women (aPR, 1.40 [95% CI, 1.34-1.47]), individuals without a spouse (aPR, 1.06 [95% CI, 1.00-1.13]), uninsured (aPR, 1.16 [95% CI, 1.06-1.27]), and those with a high school education (aPR, 1.17 [95% CI, 1.12-1.23]), cardiovascular disease (aPR, 1.17 [95% CI, 1.09-1.25]), depressive disorder (aPR, 1.41 [95% CI, 1.34-1.48]), chronic obstructive pulmonary disease (aPR, 1.33 [95% CI, 1.24-1.43]), asthma (aPR, 1.28 [95% CI, 1.21-1.35]), and kidney disease (aPR, 1.11 [95% CI, 1.01-1.21]). Long COVID was less prevalent among non-Hispanic Black (aPR, 0.87 [95% CI, 0.81-0.95]), students (aPR, 0.87 [95% CI, 0.76-0.99]) or retired individuals (aPR, 0.89 [95% CI, 0.82-0.98]), and those with household incomes ≥$100,000 (aPR, 0.85 [95% CI, 0.79-0.92]).

CONCLUSIONS: Long COVID affects 7.2% of US adults, with higher vulnerability among women, middle-aged individuals, White individuals, socioeconomically disadvantaged groups, and those with chronic conditions. These findings underscore the need for targeted public health strategies to address disparities in long COVID burden and support high-risk populations.

RevDate: 2025-05-13

Ono BE, Izaias JE, Sales AO, et al (2025)

Sympathetic Neural Overdrive, Vascular Dysfunction and Diminished Exercise Capacity in Long COVID-19 Patients: A Long-Term Study of Cardiovascular Sequelae.

American journal of physiology. Regulatory, integrative and comparative physiology [Epub ahead of print].

Background: We have recently showed that severe COVID patients have neurovascular dysfunction, cardiac morpho-functional alterations, and attenuated exercise capacity. However, whether these alterations persist over time is unknown. Here, we tested the hypothesis that Long COVID patients, even 2 years after SARS-COV-2 infection, exhibit sympathetic overdrive, aortic stiffening, endothelium-dependent dysfunction, cardiac morpho-functional changes, and diminished exercise capacity. Methods: Eighteen Long COVID patients and 19 well-matched controls were studied. Muscle sympathetic nerve activity (MSNA; microneurography), brachial artery flow-mediated dilation (BAFMD; ultrasound-Doppler), carotid-femoral pulse wave velocity (CFPWV; tonometry), heart rate (HR; EKG), E/A ratio, left ventricular ejection fraction and global longitudinal strain (LVEF, LVGLS; echocardiography), and peak oxygen uptake (Peak V̇O2, cardiopulmonary exercise testing) were assessed ⁓2 years after hospital discharge. Circulating angiotensin II (Ang II, mass spectrometry), endothelial cell-derived extracellular vesicles (endothelial cell-derived EVs, flow cytometry), and oxidative stress were also evaluated. Results: Long COVID patients had higher MSNA, CFPWV, HR and lower E/A ratio, LVEF, LVGLS and Peak V̇O2 than controls. Endothelial cell-derived EVs and carbonyls were higher in Long COVID patients than controls, whereas superoxide dismutase (SOD) was lower. No difference was observed in Ang II. Peak V̇O2 was inversely associated with MSNA, LVGLS and carbonyls, and directly associated with BAFMD and SOD. Conclusions: Our findings reveal that Long COVID patients, 2 years after acute illness, exhibit persistent sympathetic overactivation, vascular and cardiac impairments, reduced exercise capacity, and increased endothelial cell-derived EVs and oxidative stress. As such, strategies that can resolve these persistent cardiovascular sequelae are urgently needed.

RevDate: 2025-05-13

Bouton M, McKenna R, Freeman-Hildreth Y, et al (2025)

A pilot study of PAs in leadership: Exploring pathways, barriers, and support systems.

JAAPA : official journal of the American Academy of Physician Assistants pii:01720610-990000000-00166 [Epub ahead of print].

OBJECTIVES: The objectives of this study were to determine pathways, barriers, and support systems experienced by physician associates (PAs) in leadership.

METHODS: Focus group interviews were conducted with 20 PA leaders. Thematic evaluation revealed inductive themes. Moderate interrater agreement was achieved.

RESULTS: Most participants were female, White, and non-Hispanic, with 13 to 23 years of experience as a PA. Participants obtained leadership positions via training, dedication to service, and networking. Participants were motivated to pursue leadership roles by issues related to compensation, time, and autonomy. Biased perception of PA roles and corporate and legal issues were the most common barriers to achieving leadership positions. Participants recommended that PAs interested in leadership self-promote and that they embrace both altruism and a growth mindset.

CONCLUSION: PA leaders achieved leadership positions via dedication, networking, and training. Corporate, legal, and perceptual barriers exist. Employers and PA organizations can support PA leaders with training, compensation, protected time, and autonomy. Celebration of the value of PA leadership is needed.

RevDate: 2025-05-13

Durstenfeld MS, Leonard D, Pettee Gabriel K, et al (2025)

Association of Pre-COVID Fitness With Post-COVID Fitness and Long COVID in the Cooper Center Longitudinal Cohort Study.

Journal of the American Heart Association [Epub ahead of print].

BACKGROUND: Cross-sectional studies suggesting that SARS-CoV-2 infection and long COVID are associated with reduced cardiorespiratory fitness (CRF) lack preinfection CRF measures. The objective of this study was to determine the association of SARS-CoV-2 infection and long COVID with change in CRF.

METHODS: Cooper Center Longitudinal Study is a cohort study based at the Cooper Clinic, a preventive medicine clinic in Dallas, Texas; we included adults ages 20 to 74 years old with CRF assessed at least twice between 2017 and 2023. COVID status was defined as "prepandemic" (2 CRF measures pre-2020), "uninfected" (no self-reported COVID), "recovered" (self-reported COVID with symptoms ≤3 months), or "long COVID" (self-reported COVID with symptoms >3 months). CRF was estimated in metabolic equivalents via a maximal modified Balke treadmill protocol.

RESULTS: We included 4005 participants (mean age: 51.8 years, 26.8% women), of whom, 1666 (41.6%) reported COVID and 80 (4.8% of infected) reported long COVID along with 1826 uninfected and 513 pre-pandemic controls. At baseline, those who later developed long COVID had lower CRF (10.0 metabolic equivalents, 11.1 recovered, 10.7 uninfected, 11.3 prepandemic; P<0.001). All groups exhibited minor decreases in CRF (~0.2 metabolic equivalents; P<0.001 for each). CRF decreased slightly more among the infected (-0.1 metabolic equivalents greater decrease [95% CI, -0.1 to 0.0]; P=0.02) but not by long COVID status (P=0.10).

CONCLUSIONS: Pre-COVID fitness, on average, is lower among people who developed long COVID. COVID does not greatly accelerate age-related declines in CRF, even among some with long COVID, although few included participants had severely disabling long COVID. Future longitudinal research will clarify if differences in CRF by infection status emerge over longer follow-up.

RevDate: 2025-05-12

Khandelwal Y, Ora M, Jain B, et al (2025)

Post-COVID-19 lung disease: utility of biochemical and imaging markers in uncovering residual lung inflammation and monitoring anti-inflammatory therapy, a prospective study.

European journal of nuclear medicine and molecular imaging [Epub ahead of print].

PURPOSE: Post-COVID-19 lung disease (PCLD) is a significant concern following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. PCLD encompasses persistent debilitating respiratory symptoms and radiological changes beyond the acute disease phase. It highlights the ongoing search to identify and manage lingering diseases. This prospective study utilizes F18-Fludeoxyglucose (FDG) PET/CT to identify residual inflammatory lung lesions in PCLD. Treatment response was assessed after anti-inflammatory and antifibrotic therapies.

MATERIALS AND METHODS: Thirty patients post-severe COVID-19 pneumonia enrolled. They underwent baseline [18]F-FDG PET/CT scans to unveil residual lung inflammation lesions on FDG and CT. They received antifibrotic (Pirfenidone) and anti-inflammatory (Methylprednisolone) drugs for 6-12 weeks. They were followed up for clinical, biochemical, and imaging treatment responses.

RESULTS: Baseline [18]F-FDG PET/CT revealed ongoing lung inflammation in all PCLD (mean SUVmax: 3.8 ± 2.3 and number of segments: 8±3). The mean CT severity score was 17.7 ± 3.4 with moderate (n = 16) or severe (n = 14) disease involvement. Mild, moderate, and severe [18]F-FDG PET/CT categories were noted in the 8, 14, and 8 patients, respectively. Following treatment, a PET scan showed a significant decrease in disease extent (segments) and severity (FDG uptake) and an improvement in disease grading on imaging (97% of patients). In PET concordance, there was a significant clinical and radiological improvement with a fall in inflammatory markers (p < 0.005). Serum Ferritin and total leukocyte counts were significantly associated with PCLD severity on [18]F-FDG PET/CT(p < 0.05).

CONCLUSION: This prospective study identifies and quantifies ongoing significant residual lung inflammation in PCLD on [18]F-FDG PET/CT. Anti-inflammatory and antifibrotic drug therapy led to clinical and radiological improvement. [18]F-FDG PET/CT as a non-invasive biomarker helped manage and follow up PCLD patients.

CLINICAL TRIAL NUMBER: Not applicable.

RevDate: 2025-05-14
CmpDate: 2025-05-13

Monroy M, Amster M, Eagle J, et al (2025)

Awe reduces depressive symptoms and improves well-being in a randomized-controlled clinical trial.

Scientific reports, 15(1):16453.

Emerging evidence suggests that experiences of awe benefit health and well-being. The present investigation examined the efficacy of an awe intervention to improve the psychological health-stress, anxiety, depression, and well-being-of patients living with long COVID. The awe intervention, a Randomized-controlled Clinical Trial, was delivered in synchronous online sessions to patients, across the United States (in April 2023), who met the criteria for long COVID. Results revealed significant improvements in psychological health for those in the awe intervention (N = 30), compared to the control group (N = 38): including decreased stress, decreased depression symptoms, and increased well-being. There were no significant differences between groups in anxiety symptoms. Effect sizes ranged from medium to large (d = 0.78-0.96), demonstrating the robustness of these findings. This work is the first to document that awe can have salutary effects on psychological health, such as reducing symptoms of depression. These findings suggest that a brief awe intervention can improve psychological health in people dealing with chronic stress and physical ailments, as in the case of long COVID.Trial registration. The trial is registered at ClinicalTrials.gov (NCT05676008, 09/01/2023).

RevDate: 2025-05-12

Duong KE, Henry SS, Cabana MD, et al (2025)

Longer Term Effects of SARS-CoV-2 infection on Asthma Exacerbation.

The journal of allergy and clinical immunology. In practice pii:S2213-2198(25)00434-9 [Epub ahead of print].

BACKGROUND: The long-term impact of COVID-19 on asthma exacerbations remains unclear.

OBJECTIVE: We assessed the future risk of asthma exacerbations after SARS-CoV-2 infection in pediatric and adult asthma patients.

METHODS: We conducted a retrospective cohort study of 12,719 asthma patients with SARS-CoV-2 infection (polymerase-chain-reaction test confirmed) and 91,763 without recorded SARS-CoV-2 infection in a large urban health care system (03/1/2020-12/31/2023). After matching on observation time, age, race, and ethnicity, 1898 children and 8532 adults were included in each group (with and without COVID-19). Andersen-Gill models adjusted for covariates (e.g., allergic rhinitis, GERD, eczema, obesity, unmet social needs) were used to calculate adjusted hazard ratios (aHR) for recurrent asthma exacerbations.

RESULTS: Both hospitalized and non-hospitalized COVID-19 children with pre-existing asthma had higher exacerbation rates than controls (40.68%, 24.81%, vs. 14.70%, p<0.001) and increased risk of future exacerbations (aHR=3.29 [2.27, 4.76]; aHR=1.82 [1.51, 2.21]), p<0.001). Adults also showed increased asthma exacerbation rates in hospitalized (23.13%) and non-hospitalized (21.49%) individuals when compared with controls (10.68%), p<0.001. Similarly, both hospitalized and non-hospitalized COVID-19 adults had increased risk of future exacerbations (aHR=2.78 [2.29, 3.38]; aHR=2.13 [1.73, 2.62]). Overall, children faced higher risks than adults. Unmet social needs elevated risk of future exacerbation in children (aHR=1.36 [1.00, 1.86]) and adults (aHR=1.26 [1.04, 1.52]).

CONCLUSIONS: SARS-CoV-2 infection was associated with a higher cumulative incidence of asthma exacerbations. Patients with unmet social needs were at higher risk of exacerbation. Clinicians should prioritize preventive strategies, trigger reduction, and immunizations for patients with a history of asthma and SARS-CoV-2 infection.

RevDate: 2025-05-12

Smith AB, Greenwood D, M Sivan (2025)

Growing evidence base on condition-specific patient-reported outcomes measures for Long Covid.

RevDate: 2025-05-12

Che W, Guo S, Wang Y, et al (2025)

SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations.

Journal of advanced research pii:S2090-1232(25)00306-6 [Epub ahead of print].

INTRODUCTION: With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored.

OBJECTIVES: Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as "Long COVID", which has significantly affected millions globally.

METHODS: We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, acute inferior myocardial infarction, and acute myocarditis.

RESULTS: All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID.

CONCLUSION: Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.

RevDate: 2025-05-12
CmpDate: 2025-05-13

Kardos P, Becker S, Heidenreich KR, et al (2025)

[Specialist Guidelines of The German Respiratory Society for Diagnosis and Treatment of adult Patients Suffering from Cough].

Pneumologie (Stuttgart, Germany), 79(5):329-357.

This is the 4[th] edition of the Cough Guidelines of the German Respiratory Society written by respiratory, gastroenterology, ear-nose-throat specialists, including respiratory physiotherapists and speech pathology specialists; importantly, a patient representative was also involved.Compared with earlier versions we used a new methodology: after discussion in the guidelines group, we asked and answered the 12 most important and most frequent "key" questions regarding the clinical practice. The extent of the guideline could thus be significantly reduced.We added a short scientific background to each of the answers including the most recent references. The recommendations and statements were created in consensus and graded as strong, or weak. If sufficient literature was not available, we suggested discussing joint decisions with the patient.The 12 key questions are as follows:- Key question 1: The classification of cough (acute, i. e. up to three weeks duration; chronic, i. e. after 8 weeks duration and subacute in between) did not change, but we added "cough with or without expectoration as an additional classification aspect with therapeutic consequences.- Key question 2: Acute and subacute cough are mostly (but not exclusively) due to the common cold. They are the first or second most frequent symptom prompting patients to seek medical (or pharmacist's) care. Antibiotic therapy is strongly discouraged for common cold- Key question 3: We defined "Red flags" for mandatory immediate diagnostic for acute cough, which usually does not require such diagnostic procedures- Key question 4: Chronic cough overview of the most common causes for- Key question 5: Cough in acute SARS-CoV-2 infection and in long COVID - Key question 6: Refractory chronic cough and idiopathic chronic cough, two recently established entities were explained more in detail- Key question 7: To upper airway cough syndrome - Key question 8: Gastro-oesophageal-reflux-related cough - Key question 9: Cough-variant asthma and non-asthmatic eosinophilic bronchitis - Key question 10: Overview of drugs causing cough - Key question 11: Basic and personalized (due to the individual history) diagnostic procedures for patients with cough- Key question 12: Physiotherapy, speech therapy and pharmacotherapy for cough.

RevDate: 2025-05-12

Hawkins KL, Dandachi D, Verzani Z, et al (2025)

HIV Infection and Long COVID: A RECOVER Program, Electronic Health Record Based Cohort Study.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8128979 [Epub ahead of print].

People with HIV may be at increased risk for long COVID after acute SARS-CoV-2 infection. We investigated the association between HIV and long COVID in two large electronic health record databases. Using data from the Patient-Centered Clinical Research Network (PCORnet) and the National Clinical Cohort Collaborative (N3C) from 1/1/2018 to 4/30/2024, our analytic sample included individuals aged ≥21 years with SARS-CoV-2. All individuals were classified as having HIV or not. We estimated the adjusted odds ratio (aOR) of long COVID by HIV status using logistic regression. Multivariable models controlled for potential associated factors and used 2 cohort definitions: a computed phenotype definition or ICD-10 code-based definition. We included 1,369,896 patients from PCORnet (11,964 with and 1,357,932 without HIV) and 3,312,355 patients from N3C (23,931 with and 3,288,424 without HIV). Using the computed phenotype definition of long COVID, we noted a small, but significant, increase in odds of developing long COVID among people with compared to those without HIV (PCORnet aOR 1.09 [CI 1.04-1.14] and N3C aOR 1.18 [CI 1.13-1.23]). Using the ICD-10 definition of long COVID, there was no association between HIV and long-COVID (PCORnet aOR 1.01 [CI 0.88-1.16] and N3C aOR 1.07 [CI 0.97-1.18], respectively). In this large multicenter study, people with HIV had a modestly increased risk of long COVID when defined by a computed phenotype, but not when using ICD-10 codes. These findings suggest that long COVID may be under-recognized in people with HIV and underscore challenges in diagnosing long COVID in populations with baseline chronic conditions.

RevDate: 2025-05-14

Kuut TA, Müller F, Braamse AMJ, et al (2025)

Cognitive behavioural therapy for severe fatigue following COVID-19 in adolescents: a serial single-case observational study of five consecutively referred patients.

Behavioural and cognitive psychotherapy [Epub ahead of print].

BACKGROUND: Severe fatigue following COVID-19 is a debilitating symptom in adolescents for which no treatment exists currently.

AIMS: The aim of this study was to determine the effectiveness and feasibility of cognitive behavioural therapy (CBT) for severe fatigue following COVID-19 in adolescents.

METHOD: A serial single-case observational design was used. Eligible patients were ≥12 and <18 years old, severely fatigued and ≥6 months post-COVID-19. Five patients, consecutively referred by a paediatrician, were included. The primary outcome was a change in fatigue severity, assessed with the fatigue severity subscale of the Checklist Individual Strength, 12 weeks after the start of CBT, tested with a permutation distancing two-phase A-B test. Secondary outcomes were the presence of severe fatigue, difficulty concentrating and impaired physical functioning directly post-CBT as determined with questionnaires using validated cut-off scores. Also, the frequency of post-exertional malaise (PEM) and absence from school directly post-CBT determined with self-report items were evaluated.

RESULTS: All five included patients completed CBT. Twelve weeks after starting CBT for severe post-COVID-19 fatigue, three out of five patients showed a significant reduction in fatigue severity. After CBT, all five patients were no longer severely fatigued. Also, four out of five patients were no longer physically impaired and improved regarding PEM following CBT. All five patients reported no school absence post-CBT and no difficulties concentrating.

CONCLUSION: This study provides a first indication for the effectiveness and feasibility of CBT among adolescents with post-COVID-19 fatigue.

RevDate: 2025-05-12

Panagea E, Messinis L, Patrikelis P, et al (2025)

Persistent neuropsychological deficits in recovered COVID-19 patients: Correlations with disease biomarkers.

Applied neuropsychology. Adult [Epub ahead of print].

OBJECTIVE: Cognitive impairment, including deficits in attention, memory, executive function, and processing speed, is common in post-COVID-19 conditions, though language performance remains less studied. The present study examined the long-term effects of COVID-19 condition on cognition and language - communication, and its associations with disease severity, Body Mass Index (BMI), inflammatory markers, and quality of life.

METHOD: Nighty eight Greek participants under 65 years of age were recruited for this study. Forty-seven participants were allocated in the COVID-19 group and 51 served as cognitively healthy controls. The COVID-19 group was categorized by disease severity and long COVID status. Assessments occurred 12 weeks post-infection, with 12 patients reevaluated after another 12 weeks. Neurocognitive tests included ABCD-II, verbal fluency, CCT, SDMT, and Euro QoL EQ-5D. Blood samples were analyzed for inflammatory markers.

RESULTS: Covid-19 survivors experienced significant cognitive deficits compared to healthy controls, particularly in processing speed, memory, and verbal fluency. Long COVID patients showed notably lower scores in processing speed and QoL, compared to those without Long COVID. However, no significant differences were observed between groups on episodic memory and executive functions tasks. Cognitive deficits were associated with biomarkers such as d-dimers and C-Reactive protein, with elevated d-dimers linked to poorer performance on generative drawing and cognitive flexibility. Higher education served as a protective factor, and was associated with higher scores in tasks such as story retelling, confrontation naming, generative drawing and reading comprehension. Older age and higher Body Mass Index were associated with poorer cognitive performance, especially on processing speed. Sex appears to influence language comprehension outcomes, with males exhibiting enhanced performance on the reading comprehension-sentence task. Disease severity negatively affected performance on the Symbol Digit Modalities Test and generative naming, indicating that greater severity was linked to poorer outcomes in these domains. Follow-up evaluations of recovered COVID-19 patients revealed significant improvements in processing speed and recall, suggesting partial recovery in these areas, although some deficits persisted over time.

CONCLUSION: The study supports findings that the prolonged effects of COVID-19 markedly impaired neurocognitive functions in recovering patients, especially those with severe or long COVID syndrome. Moreover, while several cognitive domains may improve over time, many other domains remain impaired and vulnerable.

RevDate: 2025-05-13

Almoliky MA, Alsaif B, Saleh KA, et al (2025)

Long COVID Symptoms and Five Dimensions of HRQoL: A Retrospective Regional Study of Patients Recovered from COVID-19 Infection in Saudi Arabia.

International journal of general medicine, 18:2401-2416.

BACKGROUND/AIM: 10-20% of people infected with the coronavirus infection have long COVID symptoms, therefore, current research is the first regional assessment in Saudi Arabia to determine the relationship between long-term health complaints of COVID-19 survivors and health-related quality of life (HRQoL).

METHODS: The study population comprised COVID-19 infection cases registered in the Ha'il region of Saudi Arabia from the beginning of the COVID-19 pandemic until September 2022. A retrospective research design was employed, and 295 participants completed a self-report questionnaire to assess long COVID symptoms and the Arabic version of the European 5-Dimensional Quality of Life (EQ-5D). Multiple linear regression was used to evaluate the predictive role of long COVID symptoms on the HRQoL of patients by choosing (p-value < 0.05).

RESULTS: The mean (SD) age of the participants was 38 years, (67.1%) were male and (58.6%) were married. On the long COVID-19 symptoms, the highest mean values were fatigue (M=2.3; 95% CI 2.1-2.4) followed by headache (M=2.1; 95% CI 2.0-2.3) and persistent cough (M=1.9; 95% CI 1.8-2.1). Findings show that HRQoL was problematic in domains of pain/discomfort as depicted by a highest mean score on this domain (M=4.24; 95% CI 4.14-4.33) followed by anxiety/depression (M=4.17: 95% CI 4.08-4.27). Multiple regression analysis showed that marital status (p=0.05), irregular exercise (p<0.01), duration of hospitalization (p<0.01), and oxygen therapy (p<0.05) were the independent background factors affecting HRQoL post-COVID-19. Among the long-COVID-19 symptoms, fatigue (p=0.05), persistent cough (p=0.001), dyspnea (p=0.02), and sexual dysfunction (p<0.001) were the independent factors that impacted the HRQoL after controlling for background variables.

CONCLUSION: The study has significant implications for Saudi Arabia's Health Sector Transformation Program that could achieve its goals of human centric care and patient satisfaction though addressing the negative impacts of specific long-COVID symptoms such as fatigue, persistent cough, dyspnea and sexual dysfunction and improving the HRQoL in domains of pain/discomfort and anxiety/depression.

RevDate: 2025-05-13

Kok LHJ, Gu JT, Kung JTY, et al (2025)

User experiences of patients with post-acute COVID-19 syndrome receiving occupational therapy telerehabilitation.

Frontiers in human neuroscience, 19:1551631.

BACKGROUND: Patients with post-acute COVID-19 syndrome, also referred to as "long COVID," may face persistent physical, cognitive and psychosocial symptoms which can be challenging to manage given the strict social distancing measures imposed during the pandemic. Telerehabilitation (TR) became increasingly common during COVID-19 pandemic and has been applied to post-acute COVID-19 conditions in previous clinical studies, and it was reported that patients' symptoms were alleviated and their overall health improved. This study examined the usability and acceptability of TR by occupational therapists delivered for patients suffering from post-acute COVID-19 in Hong Kong.

METHODS: In this mixed-methods usability study, participants rated items on the System Usability Scale (SUS) and completed a semi-structured questionnaire via audio-recorded telephone calls. Descriptive data were used to summarize the quantitative data, and thematic analysis was applied to analyze the qualitative data.

RESULTS: Twelve participants (mean age 56.5 years) who had completed a 6-week TR program via the Caspar Health system were recruited for the study. A median SUS score of 56.25 was reported for its usability, despite 83% of the participants viewed the TR system as fairly acceptable. Four themes, namely perception of using the TR system - performance expectancy of TR, other psychosocial and environmental factors, and intention to use TR, were generated on the basis of the participants' interviews. Most participants reported their willingness to continue using TR and that they would recommend it to other patients.

CONCLUSION: Most of the participants were receptive to TR and perceived health benefits from its use. Future research could consider integrating the perspectives of both occupational therapists and patients to generate a more comprehensive understanding of the facilitators of and the barriers to TR for patients who experience long COVID.

RevDate: 2025-05-12

Rezende AG, Valente J, Goulart CDL, et al (2025)

Does long COVID in people living with HIV resemble the functional phenotype of non-HIV individuals who had moderate or severe acute COVID-19? A retrospective cross-sectional study.

Frontiers in medicine, 12:1533009.

INTRODUCTION: It has been postulated that individuals with long COVID have reduced exercise capacity, just as people living with HIV (PLWH), although having even lower exercise capacity. The extent to which long COVID in PLWH resembles long COVID in individuals who presented different COVID-19 phenotypes is unknown, so we aimed to determine if the long COVID profile in PLWH resembled the symptoms experienced by individuals with long COVID following mild/moderate or severe acute COVID-19, 2 years after the initial disease.

MATERIAL AND METHODS: A pulmonary function test and a 6-min walk test (6MWT) were performed on adult individuals with PACS (Post-Acute COVID Syndrome) in 3 groups: COVID-19+PLWH (plwHCOV), mild/moderate COVID-19 (mmCOV); severe COVID-19 (seCOV).

RESULTS: Sixty three individuals were included: plwHCOV (n = 12), mmCOV (n = 33) and seCOV (n = 18). Across all groups, males were predominant. BMI was 25 ± 3, 28 ± 4, and 32 ± 7 kg/m[2] in plwHCOV, mmCOV, and seCOV, respectively (p = 0.003). The plwHCOV walked 545 m (±93) at the 6MWT, which was comparable to the mmCOV group (555 m ± 63) but significantly higher than the seCOV group (435 m ± 84) (p < 0.0001). The plwHCOV group had worse forced expiratory volume in 1st second (FEV1%, 80 ± 12) (p < 0.0001), forced vital capacity (FVC%, 83 ± 11) (p = 0.002) and FEV1/FVC (0.80 ± 0.1, p = 0.004) when compared to the seCOV group. Interestingly, PLWH had comparable 6MWT, FEV1, FVC, and FEV1/FVC results as mmCOV.

CONCLUSION: Our results indicate that even 2 years post-COVID-19 infection, PLWH exhibits significantly decreased spirometry compared to the seCOV group. Despite this lung function impairment, their functional capacity was similar to individuals with PACS following mild/moderate COVID-19.

RevDate: 2025-05-12
CmpDate: 2025-05-12

Iijima H, Funaki T, M Kubota (2025)

Long-COVID in children and their parents: A prospective cohort study.

Pediatrics international : official journal of the Japan Pediatric Society, 67(1):e70042.

BACKGROUND: Long-COVID is a significant global health concern, regardless of age. However, few reports have longitudinally evaluated the characteristics, prevalence, and risk factors of long-COVID in children.

METHODS: Participants were Japanese children younger than 18 years hospitalized for COVID-19 between November 2021 and October 2022, along with their COVID-19 affected parents. During hospitalization and at 1-, 3-, and 6-month follow-ups, participants completed age-appropriate questionnaires on long-COVID symptoms. The quality of life (QOL) score was assessed in children older than 2 years. The prevalence of long-COVID symptoms by age group was compared. Multivariable logistic regression analysis was conducted to investigate risk factors affecting long-COVID. Analysis of covariance adjusted for potential confounders was conducted to determine which symptoms affect QOL score.

RESULTS: Of 108 children enrolled, the prevalence of long-COVID was 44.9%, 37.8%, and 22.8% at 1, 3, and 6 months, respectively, after SARS-CoV-2 infection. There were no specific risk factors for long-COVID. Cough, fatigue, and sleep disturbance were the most common long-COVID symptoms, with sleep disturbance associated with a change in lower QOL score from admission at all three follow-ups (mean difference 9.25, 20.15, and 19.81; 95% CI, 1.58-16.91, 3.38-36.92, and 5.51-34.11). The prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms among 0-6 years was significantly lower than among 7-17 years and parents; there was no significant difference between 7 and 17 years and parents.

CONCLUSION: Even 6 months after SARS-CoV-2 infection, 22.8% of pediatric patients still had long-COVID symptoms. Some of these symptoms were similar to those of ME/CFS, potentially affecting children's QOL.

RevDate: 2025-05-12
CmpDate: 2025-05-12

Sullivan DL, Goddard K, Kurth NK, et al (2025)

"I'm in Hell …": Experiences of Unmet Health Care Needs Among People with Pre-Existing Disability and Long COVID.

Journal of health care for the poor and underserved, 36(2):572-589.

The unmet health care needs of people with pre-existing disabilities who have long COVID are understudied. During the COVID-19 pandemic, people with disabilities experienced barriers to accessing care and supplies needed to prevent and treat COVID-19. Once they had contracted COVID-19, people with disabilities were more likely to develop long COVID compared with people without disabilities. Using the 2022 National Survey on Health and Disability, this study aimed to compare how unmet health care needs differ among people with pre-existing disabilities with and without long COVID. We examined bivariate associations between unmet health care needs and respondents' demographic characteristics and responses to open-ended survey questions. About 73% of respondents with long COVID reported unmet health care needs compared with 62.6% of respondents without long COVID. Four key themes emerge from open-ended responses: exacerbation of existing disability, navigating the health care system, gaslighting by health care providers, and financial burdens.

RevDate: 2025-05-12

Juliet S D, B J (2025)

Prescriptive analytics decision-making system for cardiovascular disease prediction in long COVID patients using advanced reinforcement learning algorithms.

Journal of X-ray science and technology [Epub ahead of print].

In recent years Covid-19 impact is causing unprecedented difficulties worldwide, affecting lifestyle choices. The post-pandemic era has made this even more critical.COVID-19 triggers widespread inflammation throughout the body, potentially causing damage to the heart and other vital organs. Mortality data from COVID-19 clearly show that the highest death rates occur in individuals with chronic conditions, such as diabetes, pneumonia, cardiovascular disease (CVD), and acute renal failure.CVD is a particular concern in the medical field. The early detection of CVD remains a significant challenge, as early identification can prompt lifestyle changes and ensure appropriate medical interventions when needed. Individuals with CVD are at an increased risk for heart attack and other serious complications. There is a limited amount of data available to study the effects of COVID-19 on CVD in COVID-19 patients. However, it is essential to monitor these patients to ensure full recovery without complications. The proposed system is specifically designed for individuals experiencing prolonged symptoms following a COVID-19 infection, commonly referred to as long COVID patients. This research introduces a novel Decision-Making System for CVD Prediction, utilizing an improved dual-attention residual bi-directional gated recurrent neural network unit (DA-ResBiGRU) algorithm with AI-Biruni Earth Radius Optimization (ABER). The proposed system employs state-of-the-art predictive algorithms and real-time monitoring to assess individual patient risk profiles accurately. This research addresses the critical need for personalized risk assessment in patients with long-term COVID, aiming to assist healthcare providers in timely and targeted interventions. By analyzing intricate patterns in patient data, the decision-making system enhances the precision of CVD prediction. Additionally, the system's adaptive nature allows it to continuously learn from new patient data, ensuring that its predictions remain up-to-date and reflective of the evolving understanding of long COVID-related cardiovascular risks. The simulation findings of this research highlight the potential of the proposed algorithm to be integrated into clinical decision-making, helping healthcare professionals identify high-risk patients more effectively. The proposed method outperformed existing algorithms, such as Deep Neural Network (DNN), Long short-term memory (LSTM), Inception-v3, Xception, and MobileNetV2, achieving the highest accuracy (97.88%), sensitivity (95.50%), specificity (94.29%), precision (96.68%), and F-measure (95.85%).

RevDate: 2025-05-11

Peter RS, Eble L, Nieters A, et al (2025)

Symptom Burden and Post-COVID-19 Syndrome 24 Months Following SARS-CoV-2 Infection: Longitudinal Population-Based Study.

The Journal of infection pii:S0163-4453(25)00094-5 [Epub ahead of print].

OBJECTIVES: To describe the symptom burden and associated impairment two years after SARS-CoV-2 index infection.

METHODS: Participants of an earlier large population-based survey in Southwestern Germany (August - September 2021) were contacted again in November 2023. We calculated the prevalences of suspected PCS and specific symptom clusters at both time points and investigated factors for their resolution or emergence.

RESULTS: A total of 6635 subjects (mean age 46.6 years, 60.9% females) participated at follow-up. Between baseline and follow-up (median 8.7 and 23.9 months after infection) there were only small changes in the point prevalence of post-COVID-19 syndrome (PCS) (29.9% versus 31.2%) or defined symptom clusters such as fatigue (23.8% versus 22.0%), neurocognitive impairment (15.8% versus 17.3%), or chest symptoms (14.4% versus 13.7%). Probabilities of resolution were often similar to probabilities of emergence, e.g. fatigue symptoms resolved in 9.8% of participants but emerged in 8.0%. Consistent predictors for emerging symptom clusters were female sex, obesity and medical treatment of the acute infection. The six main symptom clusters together explained 45% (physical domain) and 29% (mental domain) of the variance in health-related quality of life (hrQoL).

CONCLUSIONS: We found a remaining high symptom prevalence two years after SARS-CoV-2 infection, but symptoms present nine months after index infection often resolved, which was associated with increasing hrQoL. Remarkably, a considerable portion of symptoms newly emerged, of which only few could be attributed to reported SARS-CoV-2 reinfection.

RevDate: 2025-05-11

Yagi K, Kondo M, Terai H, et al (2025)

Impact of long COVID on the health-related quality of life of Japanese patients: A prospective nationwide cohort study.

Respiratory investigation, 63(4):610-616 pii:S2212-5345(25)00065-6 [Epub ahead of print].

BACKGROUND: Various prolonged systemic symptoms, forming the long coronavirus disease (COVID), have been observed in patients who have recovered from the acute phase of COVID-19. Although previous studies have reported that COVID-19 impacts health-related quality of life (HRQoL), the associations of long COVID symptoms and clinical characteristics with HRQoL remain unclear. This study aimed to clarify these associations using nationwide Japanese epidemiological data.

METHODS: A prospective nationwide cohort study was conducted on patients with COVID-19 between January 2020 and February 2021 at 26 participating medical institutions in Japan. Various long COVID symptoms and HRQoL scores at 3, 6, and 12 months following diagnosis were collected from 986 participants. Generalized estimating equations (GEE) were used to explore the association between HRQoL scores evaluated using the short form-8 (SF-8), long COVID symptoms, and baseline clinical characteristics.

RESULTS: Patients who had one long COVID symptom showed a significantly lower physical component summary score (PCS) and mental component summary score (MCS) compared with those without any symptoms at all time points after diagnosis. GEE revealed that long COVID symptoms, including dyspnea, fatigue, headache, and muscle weakness, were significantly associated with worse PCS, whereas poor concentration, sleep disorders, fatigue, and headache were significantly associated with worse MCS. Severity-related baseline parameters for patients with COVID-19 were significantly associated with worse PCS scores, although these factors were not significantly associated with worse MCS scores.

CONCLUSIONS: Long COVID symptoms were associated with lower physical and mental HRQoL. Severe outcomes of COVID-19 impacted PCS but not MCS.

RevDate: 2025-05-12

Grady CB, Bhattacharjee B, Silva J, et al (2025)

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Communications medicine, 5(1):163.

BACKGROUND: The symptomatic and immune responses to COVID-19 vaccination of people with Long COVID are poorly characterized.

METHODS: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination.

RESULTS: At 12 weeks post-vaccination, self-reported improved health is seen in 10 out of 16 participants, 3 have no change, and 3 have worse health although 2 report transient improvement after vaccination. One participant reporting worse health was hospitalized twice with chest pain (after each dose). Symptom outcomes are most associated with plasma biosignatures. Higher baseline sIL-6R is associated with symptom improvement, and stably elevated levels of IFN-β and CNTF are associated with no improvement. Significant elevation in SARS-CoV-2-specific TCRs and spike protein-specific IgG are observed at 6 and 12 weeks after vaccination. No changes in reactivities are observed against herpes viruses and self-antigens.

CONCLUSIONS: In this study of 16 people with Long COVID, vaccination is associated with increased SARS-CoV-2 spike protein-specific IgG and T cell expansion in most participants. Specific immune features are associated with symptom change after vaccination and most participants experience improved health or no change following vaccination.

RevDate: 2025-05-11
CmpDate: 2025-05-10

Gierthmuehlen M, PC Gierthmuehlen (2025)

COVIVA: Effect of transcutaneous auricular vagal nerve stimulation on fatigue-syndrome in patients with Long Covid - A placebo-controlled pilot study protocol.

PloS one, 20(5):e0315606.

BACKGROUND: Up to 80% of patients who develop coronavirus disease-2019 (Covid-19) infection subsequently experience long covid/post-covid syndrome. The World Health Organization (WHO) has estimated that >770 million patients have been infected with Covid-19 globally. Even if only 10% of these patients develop long covid, > 75 million patients will suffer for a long period. Among the various symptoms of post-covid syndrome, fatigue is common, affecting up to 60% of the patients. As observed in other viral infections, elevated levels of inflammatory cytokines may play a role. Transcutaneous auricular vagal nerve stimulation (taVNS) is a noninvasive method that modulates the immune system via the central nervous system and has shown promising effects in autoimmune diseases and improving fatigue. In this pilot study, we investigated the feasibility of daily taVNS in patients with long covid-related fatigue. Additionally, the effects of taVNS on fatigue and quality of life will be analyzed.

METHODS: A total of 45 adult patients with long covid associated fatigue syndrome will be enrolled in this study, and will be randomized to the above-threshold-stimulation, below-threshold-stimulation, or sham-stimulation arms, after being informed that they will feel the stimulation. The above-threshold-group will receive a 4-week-long left-sided cymba conchae taVNS with 25 Hz, 250 µs pulse width 28s/32s on/off paradigm for 4 h throughout the day. The below-threshold group will receive stimulation below the sensational threshold, whereas the sham group will receive no stimulation following application of a non-functional electrode. The daily stimulation protocol will be recorded either manually or using the provided app. Three well-established questionnaires, the Multidimensional-Fatigue-Inventory-20, Short-Form-36, and Beck-Depression-Inventory, and the newly established Post-Covid-Syndrome-Score will be completed both before and after 4 weeks of stimulation.

DISCUSSION: The primary endpoint has been set as the patients' average daily stimulation time after 4 weeks, while secondary endpoints include the effects of taVNS on fatigue and Quality of Live (QoL). As a non-invasive treatment option, taVNS may be a notable alternative for patients with post-covid related fatigue.

TRIAL REGISTRATION: This study was approved by the local ethics committee (23/7798) and registered (DRKS00031974) (see supporting information files).

ETHICS & DISSEMINATION: The ethical justifiability of this study was supported by prior research demonstrating the safety of taVNS. Patients will be recruited by general practitioners, and written informed consent will be obtained. All data will be pseudonymized for collection and storage. The study results will be published in peer-reviewed journals with the aim of providing evidence of the potential of taVNS in long covid management. The study will be conducted in accordance with the principles of the Declaration of Helsinki.

RevDate: 2025-05-12

Opielinski LE, Uhrich TD, Haischer MH, et al (2025)

COVID-19 and the impact of physical activity on persistent symptoms.

Frontiers in sports and active living, 7:1560023.

INTRODUCTION: Physical activity is protective against chronic disease but whether activity is associated with persistent symptoms in non-hospitalized coronavirus disease 2019 (COVID-19) survivors is unknown. The purpose of the study was to determine the impact of the COVID-19 pandemic on physical activity levels and the influence of physical activity on acute COVID-19 and long COVID symptoms in non-hospitalized COVID-19 survivors.

METHODS: In total, 64 non-hospitalized COVID-19 survivors (45 female participants, 40 ± 18 years) were assessed for activity levels, body composition, and symptoms of COVID-19 8.5 ± 4.7 months post-infection and categorized into two groups: (1) persistent symptoms and (2) no symptoms at the time of testing. Furthermore, 43 of the 64 participants (28 female participants, 46 ± 18 years) completed a follow-up questionnaire online 51.0 ± 39.7 months (4.25 years) post-infection. A subset of 22 COVID-19 survivors (16 female participants, 35 ± 16 years) were matched for age, sex, and body mass index with healthy controls. Physical activity was quantified using (1) self-reported questionnaire (International Physical Activity Questionnaire; IPAQ-SF) at three time periods; prior to COVID-19 infection, at the time of laboratory testing (8.5 ± 4.7 months after infection), and during an online follow-up (51.0 ± 39.7 months, i.e., 4.25 years after infection); and (2) 7 days of wearing an ActiGraph accelerometer following laboratory testing.

RESULTS: Physical activity (IPAQ-SF) declined in COVID-19 survivors from pre-COVID-19 infection to 8.5 ± 4.7 months after infection [3,656 vs. 2,656 metabolic equivalent of task (MET) min/week, 27% decrease, p < 0.001, n = 64] and rebounded to levels similar to pre-COVID-19 infection at 4.25 years after infection (p = 0.068, n = 43). Activity levels quantified with accelerometry did not differ between COVID-19 survivors and controls. However, COVID-19 survivors who reported persistent symptoms 8.5 months after infection (n = 29) engaged in less moderate-vigorous physical activity and steps/day than those without persistent symptoms (n = 27) (37 vs. 49 MET min/day, p = 0.014 and 7,915 vs. 9,540 steps/day, p = 0.014).

DISCUSSION: Both COVID-19 survivors and matched controls reported reductions in physical activity indicating that lower levels of activity were likely due to the pandemic rather than COVID-19 infection alone. However, those who were most affected by COVID-19 infection with persistent symptoms had the greatest reductions in physical activity, even at ∼8 months and ∼4 years post-infection.

RevDate: 2025-05-11

Tsui CM, Chan SC, Lam LF, et al (2025)

Impact of Long COVID symptoms on individuals in Hong Kong: Implications for occupational therapy practices.

The British journal of occupational therapy, 88(3):158-165.

INTRODUCTION: From occupational therapy perspective, this study investigates the nature and impact of Long COVID symptoms on individuals in Hong Kong according to their gender, age, and occupation and to understand their treatment needs.

METHOD: A total of 193 participants with an acute COVID-19 episode 3 months ago and having recovered from it who were experiencing subjective symptoms of Long COVID were recruited through snowball sampling from local COVID-19 support groups and healthcare facilities to participate in a cross-sectional design via an online survey assessing their symptoms and the impact on daily activities, and exploring their treatment preferences.

FINDINGS: Respiratory, systemic, sleep, and cognitive symptoms were found to be the most prevalent, with significant variations in symptom severity and impact on daily life across different age and occupational status groups. The treatment preference was quite strongly inclined to traditional Chinese medicine.

CONCLUSION: This study has uncovered the critical and yet recognized roles of occupational therapy in managing Long COVID impact by identifying the potential gaps of occupational therapy in its management and calling for advocating promotion in the community and interdisciplinary collaboration with traditional Chinese medicine. Implications about occupational therapy management and the healthcare policies for tailoring treatment programs are discussed.

RevDate: 2025-05-12

Ongaya A, Cardenas AR, Shiluli C, et al (2025)

Prevalence of Long COVID in Mycobacterium tuberculosis-exposed Groups in Peru and Kenya.

medRxiv : the preprint server for health sciences.

BACKGROUND: Long COVID (LC), also referred to as post-COVID condition, refers to new or worsening symptoms lasting more than three months after SARS-CoV-2 infection. The prevalence of LC, and the impact of co-infection with prevalent pathogens such as Mycobacterium tuberculosis (Mtb), in low- and middle-income countries remain unclear. We aimed to address these gaps in two Mtb-exposed populations.

METHODS: We recruited HIV-uninfected pulmonary tuberculosis (TB) patients (n=36) and their household contacts (n=63) in Peru, and healthcare workers (n=202) in Kenya. We collected clinical data using study instruments adapted from a United States based study of LC. Participants were sampled within 2 years of SARS-CoV-2 diagnosis.

RESULTS: In Peru, 41.4% participants reported LC symptoms, with no TB-associated significant differences in the prevalence or clinical phenotypes of LC. The most common LC symptoms were neurological (e.g., headache and trouble sleeping) and musculoskeletal (e.g., back pain). Kenyan participants reported acute, but no LC symptoms, and reported a decline in the quality of life during acute infection. In Peru, the post-COVID-19 period was associated with a significant decline in all quality-of-life dimensions (p<0.01), except depression and anxiety (p=0.289).

CONCLUSION: This study shows that LC prevalence was high in Peru, where TB status was not linked to LC symptoms. Those with LC reported high levels of musculoskeletal and neurological symptoms. Unexpectedly, healthcare workers in Kenya denied the presence of LC symptoms. These findings highlight the need for long-term follow-up and larger studies in different geographic settings to dissect the impact of TB comorbidity on LC.

RevDate: 2025-05-11
CmpDate: 2025-05-10

Tawfiq E, Chen R, Honeyman DA, et al (2025)

Long Covid Symptom Clusters, Correlates and Predictors in a Highly Vaccinated Australian Population in 2023.

Health expectations : an international journal of public participation in health care and health policy, 28(3):e70273.

BACKGROUND: Limited data exists regarding long Covid burden following Omicron infection in highly vaccinated populations.

OBJECTIVE: To (1) characterise long Covid prevalence and predictors and (2) identify key symptom clusters and their correlates among long Covid patients, during an Omicron-predominant period in a highly vaccinated population.

DESIGN: Anonymous, online, cross-sectional survey.

SETTING: January 2023, Australia.

PARTICIPANTS: Residents aged ≥ 18 years with self-reported history of test-positive Covid-19. The main variables studied were socio-demographic characteristics, Covid-19 risk factors, vaccination, infection history and experiences with long Covid.

MAIN OUTCOME MEASURES: Long Covid symptoms. Symptom-based clustering was used to identify long Covid symptom clusters and their functional correlates. Predictors of long Covid occurrence and severity were assessed using multivariable logistic regression.

RESULTS: Overall, 240/1205 participants (19.9%) reported long Covid. Long Covid risk was significantly higher for women OR 1.71 (95% CI: 1.17-2.51), people with comorbidities 2.19 (95% CI: 1.56-3.08) and those using steroid inhalers for Covid-19 treatment (2.34 [95% CI: 1.29-4.24]). Long-Covid risk increased with increasing Covid-19 infection severity (moderately severe symptoms: 2.23 [95% CI: 1.50-3.30], extremely severe symptoms: 5.80 [95% CI: 3.48-9.66], presented to ED/hospitalised: 7.22 [95% CI: 3.06-17.03]). We found no significant difference in the likelihood of long Covid between the Omicron and pre-Omicron periods, vaccination status and participant age. We identified two long Covid clusters (pauci-symptomatic, n = 170, vs. polysymptomatic, n = 66). Polysymptomatic cluster membership was associated with worse functioning (impacts on work, moderate activity, emotions and energy). Severity acute infection was strongly predictive of polysymptomatic cluster membership (5.72 [2.04-17.58]). Monoclonal antibody treatment was strongly associated with pauci-symptomatic cluster membership (0.02 [0.00-0.13]).

DISCUSSION: Our study shows that long Covid is an important health burden in Australia, including during the Omicron era, and identifies several risk factors. We found a subgroup of patients characterised by more symptoms and worse functional outcomes. Our findings can inform policies for protecting vulnerable populations and frameworks for long Covid risk assessment and management.

CONCLUSIONS: One-in-five people may suffer long Covid after acute Covid-19 infection, with similar risk across age groups. Omicron variants appear not to have a lower risk compared to earlier variants in our study. A cumulative number of symptoms can help triage long Covid patients.

We did not involve patients or the public in the design of the questionnaire. However, after a soft launch, we revised some survey questions by reviewing early responses from patients and the public.

RevDate: 2025-05-11
CmpDate: 2025-05-09

Ho L, Kwong MH, Yuen KW, et al (2025)

Understanding intentions to use a multi-component supported self-management platform for long COVID-19: a mixed-methods evaluation in Hong Kong.

Scientific reports, 15(1):16086.

A culturally appropriate, multi-component self-management platform was developed to facilitate Long COVID-19 recovery in Hong Kong, comprising a smartphone application, a website, and a customer relationship management (CRM)-based messaging system. Using a mixed-methods design, we evaluated users' intentions to utilise the platform through the behavioural attributes of the Meta-UTAUT (Meta-analysis-based modified Unified Theory of Acceptance and Use of Technology) framework. Structured interviews were conducted to explore themes influencing users' intentions to use the platform, focusing on different attributes. Themes from the interviews were summarised using directed content and thematic analyses. These results informed the design of a cross-sectional survey quantifying the influence of those attributes on users' utilisation of the platform. Multivariate logistic regressions were conducted to investigate the associations between sociodemographic and health characteristics and the likelihood of responses to each attribute. Analysis of 45 interviews identified 17 themes influencing platform use, across six attributes: performance expectancy, effort expectancy, social influence, facilitating conditions, perceived information security, and perceived enjoyment. The survey of 326 users revealed that each of these attributes influenced the intentions of over 80% of participants using the platform. Gender, age, educational attainment, and employment status were significantly associated with their responses to specific attributes. Supported self-management is an emerging intervention for Long COVID-19. While online platforms enhance access to health information, interactions through CRM-based messaging systems may optimise professional and emotional support, thereby improving user engagement. Resources may be directed towards alleviating digital barriers, particularly for older populations.

RevDate: 2025-05-11
CmpDate: 2025-05-09

Sardell J, Pearson M, Chocian K, et al (2025)

Reproducibility of genetic risk factors identified for long COVID using combinatorial analysis across US and UK patient cohorts with diverse ancestries.

Journal of translational medicine, 23(1):516.

BACKGROUND: Long COVID is a major public health burden causing a diverse array of debilitating symptoms in tens of millions of patients globally. In spite of this overwhelming disease prevalence, staggering cost, severe impact on patients' lives and intense global research efforts, study of the disease has proved challenging due to its complexity. Genome-wide association studies (GWAS) have identified only four loci potentially associated with the disease, although these results did not statistically replicate between studies. A previous combinatorial analysis study identified a total of 73 genes that were highly associated with two long COVID cohorts in the predominantly (> 91%) white European ancestry Sano GOLD population, and we sought to reproduce these findings in the independent and ancestrally more diverse All of Us (AoU) population.

METHODS: We assessed the reproducibility of the 5343 long COVID disease signatures from the original study in the AoU population. Because the very small population sizes provide very limited power to replicate findings, we initially tested whether we observed a statistically significant enrichment of the Sano GOLD disease signatures that are also positively correlated with long COVID in the AoU cohort after controlling for population substructure.

RESULTS: For the Sano GOLD disease signatures that have a case frequency greater than 5% in AoU, we consistently observed a significant enrichment (77-83%, p < 0.01) of signatures that are also positively associated with long COVID in the AoU cohort. These encompassed 92% of the genes identified in the original study. At least five of the disease signatures found in Sano GOLD were also shown to be individually significantly associated with increased long COVID prevalence in the AoU population. Rates of signature reproducibility are strongest among self-identified white patients, but we also observe significant enrichment of reproducing disease associations in self-identified black/African-American and Hispanic/Latino cohorts. Signatures associated with 11 out of the 13 drug repurposing candidates identified in the original Sano GOLD study were reproduced in this study.

CONCLUSION: These results demonstrate the reproducibility of long COVID disease signal found by combinatorial analysis, broadly validating the results of the original analysis. They provide compelling evidence for a much broader array of genetic associations with long COVID than previously identified through traditional GWAS studies. This strongly supports the hypothesis that genetic factors play a critical role in determining an individual's susceptibility to long COVID following recovery from acute SARS-CoV-2 infection. It also lends weight to the drug repurposing candidates identified in the original analysis. Together these results may help to stimulate much needed new precision medicine approaches to more effectively diagnose and treat the disease. This is also the first reproduction of long COVID genetic associations across multiple populations with substantially different ancestry distributions. Given the high reproducibility rate across diverse populations, these findings may have broader clinical application and promote better health equity. We hope that this will provide confidence to explore some of these mechanisms and drug targets and help advance research into novel ways to diagnose the disease and accelerate the discovery and selection of better therapeutic options, both in the form of newly discovered drugs and/or the immediate prioritization of coordinated investigations into the efficacy of repurposed drug candidates.

RevDate: 2025-05-09

Stussman B, Camarillo N, McCrossin G, et al (2025)

Post-exertional malaise in Long COVID: subjective reporting versus objective assessment.

Frontiers in neurology, 16:1534352.

BACKGROUND: Post-exertional malaise (PEM) is a central feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and has emerged as a prominent feature of Long COVID. The optimal clinical approach to PEM is inconclusive, and studies of the impact of exercise have yielded contradictory results.

OBJECTIVE: The objective of this study was to examine PEM in Long COVID by assessing the prevalence of self-reported PEM across study cohorts and symptom responses of Long COVID patients to a standardized exercise stressor. Secondarily, Long COVID symptom responses to exercise were compared to those of ME/CFS and healthy volunteers.

METHODS: Data from three registered clinical trials comprised four cohorts in this study: Long COVID Questionnaire Cohort (QC; n = 244), Long COVID Exercise Cohort (EC; n = 34), ME/CFS cohort (n = 9), and healthy volunteers (HV; n = 9). All cohorts completed questionnaires related to physical function, fatigue, and/or PEM symptoms. EC also performed a standardized exercise test (cardiopulmonary exercise test, CPET), and the PEM response to CPET was assessed using visual analog scales and qualitative interviews (QIs) administered serially over 72 h. EC PEM measures were compared to ME/CFS and HV cohorts. A secondary analysis of QI explored positive responses to CPET among EC, ME/CFS and HV.

RESULTS: Self-reported PEM was 67% in QC and estimated at 27% in EC. Only 2 of 34 EC patients (5.9%) were observed to develop PEM after a CPET. In addition, PEM responses after CPET in Long COVID were not as severe and prolonged as those assessed in ME/CFS. Twenty-two of 34 EC patients (64.7%) expressed at least one of 7 positive themes after the CPET.

CONCLUSION: Self-report of PEM is common in Long COVID. However, observable PEM following an exercise stressor was not frequent in this small cohort. When present, PEM descriptions during QI were less severe in Long COVID than in ME/CFS. Positive responses after an exercise stressor were common in Long COVID. Exercise testing to determine the presence of PEM may have utility for guiding clinical management of Long COVID.

RevDate: 2025-05-09

Mohr I, Brand M, Weber C, et al (2025)

Mental and Physical Health in Wilson Disease Patients With SARS-CoV-2 Infection and Relevance of Long-COVID.

JIMD reports, 66(3):e70021.

SARS-CoV-2 infection and Long COVID (LC) might lead to a significant deterioration of physical and mental health. Wilson disease (WD) patients have a chronic liver and/or neuropsychiatric disease, making it particularly interesting to investigate LC in WD. 51 WD patients were retrospectively examined, evaluating physical and mental health by a survey and neuropsychological tests (SF-12, PSQI, ISI, Epworth, Chalder-fatigue scale, PHQ-9, GAD-7, PSS, FLei) before and ~11 months after SARS-CoV-2 infection. LC was defined as the development of new, at least moderately severe symptoms (shortness of breath, chest pain, fatigue, brain fog, exercise capacity, concentration disturbances) and/or worsening of pre-existing symptoms. 70.6% had predominant hepatic and 29.4% had neuropsychiatric symptoms at WD diagnosis. Median age was 39 years; 56.1% were female. Patients were in stable maintenance phase with a median treatment duration of 23 years. When compared to before COVID-19, WD patients had significantly worse physical life quality, sleeping quality, and fatigue. After COVID-19, a high percentage of WD patients reported concentration disorders (60%), fatigue (55%), reduced exercise capacity (50%), shortness of breath (40%), chest pain (20%) and feeling of brain fog (15%). 39.2% (n = 20) of the WD patients were classified as LC. This LC-WD subgroup showed significantly impaired quality of life, a high stress level, and sleeping disturbances, fatigue, depression, anxiety, and cognitive impairment. A large proportion of WD patients experience LC symptoms, reduced life quality, and sleeping disorders after SARS-CoV-2 infection. WD patients post-infection should be well monitored and supported if they develop persisting symptoms or neuro-psychological problems.

RevDate: 2025-05-09

Li K, Wei Y, Hung CT, et al (2025)

Post-pandemic excess mortality of COVID-19 in Hong Kong: a retrospective study.

The Lancet regional health. Western Pacific, 58:101554.

BACKGROUND: As the COVID-19 pandemic shifted into the post-pandemic period in early 2023, following the COVID-19 normalization with relaxation of stringent control measures and high vaccination coverage in Hong Kong, its long-term impact on mortality remains challenging with necessary needs of data-driven insights. This study examined the pattern of post-pandemic excess mortality in Hong Kong.

METHODS: We analyzed weekly inpatient death data from public hospitals from January 1, 2013, to June 1, 2024, using a mixed model with over-dispersed Poisson regression. Expected mortality was estimated as the difference between observed mortality and baseline derived from pre-pandemic data. Age-stratified analyses of overall and cause-specific mortality were conducted across the pre-Omicron pandemic, Omicron, and post-pandemic periods.

FINDINGS: In the post-pandemic period, the excess mortality declined but remained six-fold higher (37.66 [95% CI: 32.72-42.60] per 100,000) than pre-Omicron level, maintaining significance after adjusting for age (32.79 [95% CI: 28.13-37.46] per 100,000). The older population experienced sustained excess mortality, with crude estimates of 100.51 and 586.74 per 100,000 among those aged 65-79 years and ≥80 years, respectively, primarily due to respiratory diseases. Younger population showed near-zero overall excess mortality, whereas increased excess mortality among them occurred in heart disease, cerebrovascular disease, and injuries.

INTERPRETATION: Our findings highlight the lasting mortality impact of pandemic among vulnerable populations, specifically the older population, possibly due to the post-COVID conditions and circulating COVID-19, suggesting the need for targeted interventions for this group.

FUNDING: Health and Medical Research Fund.

RevDate: 2025-05-07

Naik H, Zhu B, Er L, et al (2025)

Work Productivity Loss in People Living with Long COVID Symptoms over 2 years from Infection.

Journal of occupational and environmental medicine pii:00043764-990000000-00869 [Epub ahead of print].

OBJECTIVE: To evaluate the work productivity loss in people experiencing long COVID symptoms more than two years after infection.

METHODS: In a cross-sectional study, employed adults from British Columbia (BC), Canada, who had a PCR-confirmed SARS-CoV-2 infection more than two years earlier, completed an online survey incorporating the Valuation of Lost Productivity questionnaire. Long COVID status was self-reported. The data were weighted to mirror the demographic and clinical profile of COVID-19 survivors in BC.

RESULTS: Of 906 participants, 165 (18.7%) reported long COVID symptoms. These individuals reported greater total productivity loss than other COVID-19 survivors (adjusted mean difference 99.2 [95%CI 44.9-167.5] hours per 3 months).

CONCLUSIONS: Long COVID is associated with substantial work productivity loss. Given the large number of individuals affected by COVID, this has significant implications for healthcare systems, the workforce, and economies.

RevDate: 2025-05-09
CmpDate: 2025-05-08

Bae G, Yang Z, Bucci D, et al (2025)

Longitudinal lipoprotein and inflammatory mediators analysis uncover persisting inflammation and hyperlipidemia following SARS-CoV-2 infection in long COVID-19.

Metabolomics : Official journal of the Metabolomic Society, 21(3):65.

INTRODUCTION: Individuals suffering from acute COVID-19 (AC) often develop long COVID-19 (LC) syndrome that is associated with aberrant levels of lipoproteins and inflammatory mediators. Yet, these dysregulations are heterogenous due to the uncertain prevalence and require a more extensive characterization.

OBJECTIVES: This study aimed to investigate LC-associated dysregulations in inflammatory mediators and lipids by longitudinal Nuclear Magnetic Resonance (NMR) lipoprotein analysis and cytokine profiling in human blood.

METHODS: We quantitatively profiled lipoproteins and inflammatory parameters in LC patients at 5 (n = 95), 9 (n = 73), 12 (n = 95), 16 (n = 78), and 20 (n = 85) months post AC by in vitro diagnostics research (IVDr)-based NMR spectroscopy. Simultaneously, we assessed inflammatory meditators with a 13-plex cytokine panel by flow cytometry. We then compared the lipoprotein profiles with historical data from AC (N = 307) and healthy cohorts collected before the COVID-19 pandemic (N = 305), whereas the cytokine profiles were correlated with that of the AC cohort.

RESULTS: We identified 31 main and 80 significantly altered subclass lipoproteins, respectively. LC was associated with higher serum levels of very low-density, intermediate-density, low-density, high-density lipoproteins, along with triglycerides, cholesterols, and apolipoprotein a-I & a-II lipoproteins compared to the healthy cohort. We also observed significantly lower concentrations of NMR-based inflammatory parameters in LC than in AC cohort, whilst proinflammatory mediators IFN-α2, IFN-γ, TNF-α, CXCL8/IL-8, IL-12p70, IL-17 A, and IL-23 displayed significantly higher concentrations in LC compared with the AC cohort. Conversely, CCL2/MCP-1, IL-6, and IL-18 were significantly higher in the AC cohort than in LC.

CONCLUSION: Our findings demonstrate a persistent hyperlipidemic phenotype in LC alongside signs of chronic inflammation and lipoprotein metabolism that vary in states of acute and chronic inflammation.

RevDate: 2025-05-09
CmpDate: 2025-05-08

O'Mahoney LL, Routen A, Gillies C, et al (2025)

The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies.

Nature communications, 16(1):4249.

The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.

RevDate: 2025-05-07

Takaoka S, Saito H, Kawate M, et al (2025)

Exploring the presence of long COVID-like symptoms in patients with chronic pain: a large-scale internet-based cross-sectional study in Japan.

Pain pii:00006396-990000000-00895 [Epub ahead of print].

Individuals with chronic pain not only endure the direct burden of pain but also experience various symptoms, including sleep disturbances and fatigue, which deteriorate their quality of life. Notably, these symptoms closely resemble those observed in "long COVID," a prolonged health complication that can arise after coronavirus disease 2019 (COVID-19) infection. Because the similarities between chronic pain and long COVID remain unexplored, this study aimed to investigate their relationship using Japanese epidemiological data. Using the Japan COVID-19 and Society Internet Survey in 2022, which included 32,000 participants, we analyzed data on the presence of chronic pain, history of COVID-19 infection, and presence of 17 long COVID-like symptoms, including gastrointestinal upset, back pain, limb/joint pain, headache, chest pain, shortness of breath, dizziness, sleep disorder, hearing disorder, taste disorder, smell disorder, memory impairment, poor concentration, hair loss, decreased libido, fatigue, and cough. Individuals with history of COVID-19 experienced a significantly greater number of long COVID-like symptoms (median: 5) compared with those with neither COVID-19 nor chronic pain (median: 4, P < 0.001). Individuals with chronic pain alone and those with both COVID-19 and chronic pain exhibited an even greater number of symptoms (median: 8 and 9, respectively). In addition, individuals with chronic pain exhibited greater prevalence odds for 15 of the 17 symptoms than those with neither COVID-19 nor chronic pain (P < 0.001). Our findings indicate that long COVID-like symptoms are not specifically associated with COVID-19. Instead, the data suggest that chronic pain contributes as an independent risk factor for these symptoms.

RevDate: 2025-05-09
CmpDate: 2025-05-07

Abbas U, Hussain N, Tanveer M, et al (2025)

Frequency and predictors of depression and anxiety in chronic illnesses: A multi disease study across non-communicable and communicable diseases.

PloS one, 20(5):e0323126.

BACKGROUND: Depression and anxiety are among the most common mental health conditions globally that impact the lifestyle of affected individuals. Mental conditions and chronic diseases are linked to each other bidirectionally. Depression and anxiety with comorbid chronic conditions are often neglected or under-screened and possess challenges in treatment. This study aimed to know the frequency and determinants of depression and anxiety along with the severity level among common chronic communicable and non-communicable diseases.

METHODS: We enrolled 200 healthy controls and 800 cases with equal number (n = 400) of patients with communicable and non-communicable diseases. Depression and anxiety were screened through Hamilton's rating scale for depression and anxiety separately. We also measured the determinants of severe depression among patients with chronic diseases. Data was analyzed through SPSS version 23.

RESULTS: We found higher frequency of depression (31% vs 11%; p=<0.001) and anxiety (13.25% vs 6%; p = 0.021) among cases as compared to healthy controls respectively. We found higher levels of depression among participants with non-communicable diseases as compared to communicable diseases (37.25% vs 24.75%; p < 0.05) respectively. Moreover, there was a higher frequency of anxiety in participants with communicable diseases as compared to those with non-communicable diseases, but the difference was non-significant (14% vs 12.5% p = 0.081). Among non-communicable diseases the highest percentage was found among individuals with cancer (67%), followed by diabetes (38%), cardiovascular diseases (33%) and respiratory disorders (11%). Among participants with communicable diseases, the highest percentage of depression was found in patients with Tuberculosis (29%) followed by HIV/AIDS (28%), Long COVID-19 (25%) and Hepatitis B/C (17%).

CONCLUSION: There is a significantly higher percentage of depression and anxiety among participants with chronic diseases. It calls for a comprehensive approach to patient care that incorporates mental health as a fundamental aspect of the treatment and management of chronic diseases. Understanding the predictors of severe depression across different chronic conditions helps in stratifying patients who may benefit most from integrated psychiatric and psychological interventions.

RevDate: 2025-05-09
CmpDate: 2025-05-07

Rodriguez-Perez AI, Serrano-Heras G, Labandeira CM, et al (2025)

Serum angiotensin type-1 receptor autoantibodies and neurofilament light chain as markers of neuroaxonal damage in post-COVID patients.

Frontiers in immunology, 16:1571027.

INTRODUCTION: Dysregulation of autoimmune responses and the presence of autoantibodies (AA), particularly those related to the renin-angiotensin system (RAS), have been implicated in the acute phase of COVID-19, and persistent dysregulation of brain RAS by RAS-related autoantibodies may also contribute to neurological symptoms of post-COVID.

METHODS: We analyzed levels of serum and CSF RAS AA in post-COVID patients with neurological symptoms, individuals who have fully recovered from COVID-19 (after-COVID controls), and uninfected individuals, and their possible correlations with the serum marker of neuroaxonal damage neurofilament light chain (NfL) and the degrees of cognitive deficit.

RESULTS: Both in serum and CSF, levels of AA agonists of the pro-inflammatory angiotensin II type 1 receptors (AT1-AA) were significantly elevated in this cohort of neurological post-COVID patients compared to both uninfected and after-COVID controls and correlated with serum levels of NfL. Changes in serum and CSF levels of AA promoting the RAS anti-inflammatory axis (upregulation of AA agonists of AT2 and Mas receptors, downregulation of AA antagonists of ACE2) suggest upregulation of the RAS compensatory response in this cohort of neurological post-COVID patients. Post-COVID patients with more pronounced cognitive impairment exhibited significantly higher CSF levels of MasR-AA and a trend toward elevated AT2-AA. Persistent brain RAS dysregulation, particularly persistent increase in AT1-AA, and its correlation with neuroaxonal damage markers and cognitive impairment, may play a significant role in neurological symptoms associated with post-COVID. Serum levels of NfL and AT1-AA may be interesting biomarkers for the early identification of CNS involvement in patients with neurological symptoms and a history of COVID-19. However, post-COVID is a highly heterogeneous entity and may result from various underlying mechanisms. The present study includes a cohort, which may differ from other cohorts with different clinical profiles, which may show different results on NfLs and CSF RAS autoantibodies, particularly AT1-AA.

CONCLUSION: These findings highlight the potential of targeting AT1 receptors as a therapeutic strategy for mitigating cognitive deficits in post-COVID patients showing upregulated AT1-AA levels.

RevDate: 2025-05-09

Chandrasekhar T, Ravishankar C, Geethanjali A, et al (2025)

Outcomes in Patients with Long COVID-19 One Year After their Discharge from Intensive Care Units.

Cureus, 17(4):e81739.

Introduction Survivors of prolonged severe COVID-19 who are treated at ICUs are at risk for physical and psychological complications, including lung injury and multi-organ dysfunction. As the number of survivors of severe COVID-19 increases, it is necessary to understand the trajectory of the disease and the patient care needed after discharge from the ICU. This study tries to efficiently assess the long-term clinical sequelae among patients with prolonged severe COVID-19 who were admitted to the ICU, one year after their discharge. The parameters tested included the chronic obstructive pulmonary disease assessment test (CAT) score, pulmonary function tests, and laboratory data. Materials and methods The study population included 454 patients who were followed up one year after surviving ICU admission for severe COVID-19. All the patients who presented with signs and symptoms to the hospital were examined further. They underwent the necessary investigations, assessments, and systemic examinations. The results of all the laboratory and radiological investigations were reviewed. During the SARS-CoV-2 pandemic, all the patient details were entered into a hospital information management system from which the data was retrieved. Mean with standard deviation (SD) or median or interquartile ranges (IQR) were used to assess the continuous variables, whereas numbers and percentages were used for categorical variables. Statistical significance was calculated by the Chi-square test. Results The median age of the study population was 64 (IQR 57-74) years and 64.7% (294/454) were male patients. The median follow-up time was 367 days. During the follow-up period, 14.9% (68/454) of the patients were readmitted to the ICU. The mean length of hospital stay was 12 days (IQR 8-20 days). Among the readmitted patients (n=68), 17.6% (12/68) were on mechanical ventilation and the remaining 82.3% (56/68) received oxygen therapy. One patient underwent extracorporeal membrane oxygenation. The hospital mortality rate observed among these ICU survivors was 10.2%. The Health-Related Quality of Life (HRQOL) score at baseline i.e. before the ICU admission (52.5 (SD, 9.2); p<0.001) was better than that observed at the one-year follow-up (44.3 (SD, 9.5); p<0.001). Moreover, the clinical frailty scale and cognitive symptoms were significantly different at the follow up assessment versus the baseline (p<0.001). The proportion of patients with a grade of 0-2 on the Modified Medical Research Council (mMRC) dyspnea scale was almost similar at baseline and the one-year follow-up, whereas a breathlessness grade of 3-4 on the scale was observed in 39.8% of the study population. Conclusion The management of ICU survivors after severe COVID requires a multi-disciplinary approach. It includes preventive measures and rehabilitation services along with appropriate treatment strategies to relieve the residual symptoms.

RevDate: 2025-05-07

He C, Xie J, Fang W, et al (2025)

Dynamic brain glymphatic changes and cognitive function in COVID-19 recovered patients: a DTI-ALPS prospective cohort study.

Frontiers in psychology, 16:1465660.

OBJECTIVE: This study aimed to evaluate brain glymphatic function in COVID-19 recovered patients using the non-invasive Diffusion Tensor Imaging-Analysis Along the Perivascular Space (DTI-ALPS) technique. The DTI-ALPS technique was employed to investigate changes in brain glymphatic function in these patients and explore correlations with cognitive function and fatigue.

MATERIALS AND METHODS: Follow-up assessments were conducted at 1, 3, and 12 months post-recovery. A total of 31 patients completed follow-ups at all three time points, with 30 healthy controls (HCs) for comparison.

RESULTS: Compared to HCs, COVID-19 recovered patients showed a significant decline in MoCA scores at 3 months post-recovery (p < 0.05), which returned to near-normal levels by 12 months. Mental fatigue, measured by the Fatigue Assessment Scale (FAS), was significantly higher in COVID-19 patients at all follow-up points compared to HCs (p < 0.05). The DTI-ALPS index in both hemispheres showed significant differences at 3 months post-recovery compared to HCs (p < 0.001), indicating increased glymphatic activity. Longitudinal analysis revealed a peak in the DTI-ALPS index at 3 months post-recovery, which then decreased by 12 months. Correlation analysis showed a significant negative correlation between the Bilateral brain hemisphere DTI-ALPS index and MoCA scores (right side: r = -0.373, p = 0.003; left side: r = -0.255, p = 0.047), and a positive correlation with mental fatigue (right side: r = 0.275, p = 0.032; left side: r = 0.317, p = 0.013).

CONCLUSION: This study demonstrates dynamic changes in brain glymphatic function in COVID-19 recovered patients, with a peak in activity at 3 months post-recovery. These changes are associated with cognitive function and mental fatigue, suggesting potential targets for addressing neurological symptoms of long COVID. The non-invasive DTI-ALPS technique proves to be a valuable tool for assessing brain glymphatic function in this population.

RevDate: 2025-05-07
CmpDate: 2025-05-07

Smail SW, Albarzinji N, Salih RH, et al (2025)

Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.

Frontiers in cellular and infection microbiology, 15:1537456.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.

RevDate: 2025-05-07
CmpDate: 2025-05-07

Hadidchi R, Al-Ani Y, Piskun H, et al (2025)

Impact of COVID-19 on long-term outcomes in Parkinson's disease.

European journal of neurology, 32(5):e70013.

OBJECTIVES: Patients with pre-existing Parkinson's disease (PD) face higher risks of severe acute COVID-19 outcomes than matched controls, but long-term post-COVID-19 outcomes remain largely unknown. This study investigated clinical outcomes up to 3.5 years post-infection in a Bronx inner-city PD population.

METHODS: This retrospective study evaluated 3512 patients with PD in the Montefiore Health System (January 2016-July 2023), which serves a large diverse population and was an epicenter of the early COVID-19 pandemic and subsequent infection surges. Comparisons were made with PD patients without a positive SARS-CoV-2 test (defined by polymerase chain reaction test). Outcomes were post-index date all-cause mortality, major adverse cardiovascular events (MACE), altered mental status, fatigue, dyspnea, headache, psychosis, dementia, depression, anxiety, dysphagia, falls, and orthostatic hypotension. Changes in Levodopa prescriptions were also tabulated. Adjusted hazard ratios (aHR) were computed accounting for competing risks.

RESULTS: PD patients with COVID-19 had similar demographics but a higher prevalence of pre-existing comorbidities compared to PD patients without COVID-19. PD patients with COVID-19 had greater risk of mortality (aHR = 1.58 [95% CI: 1.03, 2.41]), MACE (aHR = 1.57 [1.19, 2.07]), dyspnea, fatigue, and fall compared to PD patients without COVID-19. Levodopa dose adjustment was higher post-infection in the COVID-19 cohort.

CONCLUSIONS: Among PD patients, COVID-19 was associated with a higher risk of adverse long-term outcomes. PD patients who survive COVID-19 may benefit from heightened clinical awareness and close follow-up. Findings highlight the need to improve post-COVID care for PD patients to mitigate disease progression and maintain quality of life.

RevDate: 2025-05-07

Parwani S, Upreti S, Mishra CK, et al (2025)

Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2.

Current HIV research pii:CHR-EPUB-148017 [Epub ahead of print].

Coronavirus Disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China. Des-ignated as an epidemic by the World Health Organization (WHO) on January 30, 2020, the virus quickly escalated to a global emergency, officially declared a pandemic in March 2020. With over 6 million recorded deaths and more than 200 identified symptoms in diverse individuals, the impact of COVID-19 is substantial. COVID-19 poses a greater risk to individuals with advanced HIV, while those with well-managed HIV are not at increased risk. Although COVID-19 vaccines are generally effective for people with HIV, some may experience reduced vaccine effectiveness and breakthrough infections due to suboptimal immune responses. Long COVID, affecting at least 65 million individuals, adds a layer of complexity. The virus's rapid mutation has led to diverse symptomatology, prompting adjustments in treatment guidelines. This review compre-hensively examines repurposed antiviral drug candidates against COVID-19, explores immune responses across different age groups, delves into the mechanisms of COVID-19 vaccines, and discusses potential immunosuppressants. Additionally, the focus extends to Intravenous Immu-noglobulin (IVIG), steroids, and anti-cytokine therapy as promising avenues to address cytokine release syndrome (CRS), a critical condition in COVID-19 patients.

RevDate: 2025-05-06
CmpDate: 2025-05-07

Ruß AK, Schreiber S, Lieb W, et al (2025)

Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany.

Scientific reports, 15(1):15791.

If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany. Each PCS score originally represented the weighted sum of the binary indicators of all, or a subset, of 12 PCS symptom complexes, assessed six months or later after the PCR test-confirmed SARS-CoV-2 infection of a participant. For various methodical reasons, however, the PCS scores were dichotomized along their respective median values in the present study, prior to the GWAS. Of the 6,383,167 single nucleotide polymorphisms included, various variants were found to be associated with at least one of the PCS scores, although not at the stringent genome-wide statistical significance level of 5 × 10[- 8]. With p = 6.6 × 10[- 8], however, the genotype-phenotype association of SNP rs9792535 at position chr9:127,166,653 narrowly missed this threshold. The SNP is located in a region including the NEK6, PSMB7 and ADGRD2 genes which, however, does not immediately suggest an etiological connection to PCS. As regards functional plausibility, variants of a possible effect mapped to the olfactory receptor gene region (lead SNP rs10893121 at position chr11:123,854,744; p = 2.5 × 10[- 6]). Impairment of smell and taste is a pathognomonic feature of both, acute COVID-19 and PCS, and our results suggest that this connection may have a genetic basis. Three other genotype-phenotype associations pointed towards a possible etiological role in PCS of cellular virus repression (CHD6 gene region), activation of macrophages (SLC7A2) and the release of virus particles from infected cells (ARHGAP44). All other gene regions highlighted by our GWAS did not relate to pathophysiological processes currently discussed for PCS. Therefore, and because the genotype-phenotype associations observed in our GWAS were generally not very strong, the complexity of the genetic background of PCS appears to be as high as that of most other multifactorial traits in humans.

RevDate: 2025-05-06

Hadidchi R, Al-Ani Y, Choi S, et al (2025)

Long-term outcomes of patients with a pre-existing neurological condition after SARS-CoV-2 infection.

Journal of the neurological sciences, 473:123477 pii:S0022-510X(25)00094-2 [Epub ahead of print].

OBJECTIVES: This study investigated post COVID-19 outcomes of patients with pre-existing neurological conditions up to 3.5 years post-infection.

METHODS: This retrospective study consisted of 1664 patients with COVID-19 (of which 1320 had been hospitalized for acute COVID-19) and 8985 non-COVID patients from the Montefiore Health System in the Bronx (Jan-2016 to Jul-2023). Pre-existing neurological conditions include dementia, mild cognitive impairment, multiple sclerosis, and Parkinson's disease. Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) post-COVID-19. Secondary outcomes were depression, anxiety, fatigue, headache, sleep disturbances, altered mental status, and dyspnea post-COVID-19. Multivariate Cox proportional hazards model was used to calculate adjusted hazard ratios for primary outcomes. Cumulative incidence function and Fine-Gray sub-distribution hazards model analysis were performed for secondary outcomes.

RESULTS: Patients with a pre-existing neurological disorders hospitalized for COVID-19 were more likely to die (adjusted hazard ratio = 1.90 [CI:1.57, 2.28], P < 0.005) whereas patients non-hospitalized for COVID-19 had similar mortality rate (aHR = 0.85 [CI:0.47, 1.54]. P = 0.59) compared to non-COVID patients. Patients with a neurological disorders (hospitalized for COVID-19 aHR = 1.76 [CI:1.53, 2.03], P < 0.005; not hospitalized for COVID-19: aHR = 1.50 [CI:1.09, 2.05], P = 0.01) were more likely to experience a MACE compared to non-COVID-19 patients. Blacks (aHR = 1.49) and Hispanics (aHR = 1.35) had a higher risk of post-COVID-19 MACE. Both hospitalized and non-hospitalized COVID-19 patients were more likely to develop altered mental status, fatigue, sleep disturbance, dyspnea compared to non-COVID patients (p < 0.05).

CONCLUSIONS: Patients with pre-existing neurological conditions who contracted SARS-CoV-2 were more likely to have worse outcomes compared to controls after adjusting for major competing risks. Identifying at-risk individuals could enable more diligent follow-up.

RevDate: 2025-05-06

Henning E, Musci R, Johnson SB, et al (2025)

Pediatric long COVID: relationships with premorbid history of anxiety or depression and health-related quality of life.

Journal of pediatric psychology pii:8125862 [Epub ahead of print].

OBJECTIVE: Up to 25% of youth may develop long COVID following COVID-19 infection. Mood changes are commonly reported; however, few studies use validated measures. This study describes prevalence of self-reported anxious and depressive symptoms among youth with long COVID. We also examined the association of these symptoms with prior mental health diagnosis and health-related quality of life.

METHODS: We conducted a retrospective study of pediatric patients (n = 139) evaluated in a pediatric post-COVID-19 rehabilitation clinic who met criteria for long COVID. Patients were included if they completed the Pediatric Quality of Life Inventory (PedsQL), the Multidimensional Anxiety Scale for Children, second edition (MASC 2), and/or the Children's Depression Inventory, second edition (CDI 2). Relationships between prior anxiety or mood disorder and current depressive and anxious symptoms were assessed using chi-square tests. Relationships between depressive and anxious symptoms and health-related quality of life were examined using multiple linear regression.

RESULTS: Almost 40% of patients had elevated scores for anxious or depressive symptoms. Prior anxiety or mood disorder diagnosis was associated with higher scores. Depression scores, and specifically the Ineffectiveness subscale, were inversely associated with PedsQL scores.

CONCLUSIONS: Prevalence of anxious and depressive symptoms in this clinical sample was high. Screening measures for mood and anxiety overlap with physical symptoms of long COVID and use of collateral information is recommended. The relationship between the Ineffectiveness subscale and the PedsQL warrants further investigation to evaluate if they assess the same domain or if negative perception of abilities contributes to health-related quality of life.

RevDate: 2025-05-07
CmpDate: 2025-05-06

Kraft J, Hardy A, Baustädter V, et al (2025)

Traditional Chinese medicine for post-COVID: A retrospective cohort study.

Medicine, 104(18):e42275.

Post-COVID syndrome affects at least 10% of individuals recovering from COVID-19. Currently, there is no causal treatment. This retrospective cohort study aimed to evaluate the potential of traditional Chinese medicine (TCM) in treating post-COVID symptoms. TCM physicians in Germany and Austria completed online questionnaires to retrospectively record symptoms, treatment approaches, and outcomes for patients diagnosed with post-COVID. Nine physicians collected data from 79 patients (65% female, 47 ± 16 SD). The most common TCM treatments for post-COVID were acupuncture (n = 66; 85%), Chinese pharmacological therapy (n = 61; 77%), and Chinese dietary counseling (n = 32; 41%). After an average of 7 ± 4 TCM consultations, physicians rated global symptom improvement as 62% ± 29%. Significant alleviation from the start of TCM treatment was observed in major symptoms, such as fatigue (P < .001), impaired physical performance (P < .001), and exertional dyspnea (P < .001). TCM treatment was associated with significant improvements in post-COVID symptoms, warranting further evaluation through randomized controlled studies.

RevDate: 2025-05-06

El-Naas A, Hamad O, Nair S, et al (2025)

New Onset of Type 1 and Type 2 Diabetes Post-COVID-19 Infection: A Systematic Review.

Emerging microbes & infections [Epub ahead of print].

AbstractCOVID-19 may primarily cause respiratory symptoms but can lead to long-term effects known as long COVID. COVID-19-induced diabetes mellitus was reported in many patients which shares characteristics of types 1 and 2 (T1DM and T2DM). This study aims to identify and analyze the reported cases of new onset diabetes post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of T1DM or T2DM post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 43 studies met our inclusion criteria. Our results revealed that the overall prevalence of new onset diabetes post-COVID-19 was 1.37% with higher prevalence for T2DM (0.84%) as compared to T1DM (0.017%) while the type of diabetes was not reported in 0.51% of the cases. Several risk factors for developing diabetes post-COVID-19 infection were identified including the type of SARS-CoV-2 variant, age, comorbidities and the vaccination status. The direct viral attack of the pancreatic beta cells as well as inflammation and the anti-inflammatory corticosteroids were proposed as possible mechanisms of the COVID-19 induced diabetes. A multidisciplinary approach involving endocrinologists, primary care physicians, and infectious disease specialists should be implemented in the management of post-COVID patients to address both the acute and long-term complications, including metabolic changes and risk of diabetes.

RevDate: 2025-05-06
CmpDate: 2025-05-06

Karnadipa T, Pratama AD, Pahlawi R, et al (2025)

Clinical indicators for predicting physical activity levels in long-term COVID-19: Insights from physical exertion and oxygen saturation.

Journal of bodywork and movement therapies, 42:198-204.

INTRODUCTION: Long COVID-19 syndrome, affecting approximately 80% of adults after SARS-CoV-2 infection, often reduces physical activity due to fatigue and breathing difficulties, leading to impaired physical function and lung capacity. This cross-sectional study examined predictive variables such as physical exertion, heart rate, and oxygen saturation to assess physical activity levels in adults with long COVID-19 syndrome.

METHODS: We recruited 34 adults aged 19-55 with a COVID-19 history and assigned them to the long-COVID-19 and control group. They were evaluated using the 6-Minute Walk Test, modified Borg Dyspnoea Scale, heart rate, maximum oxygen uptake, and the IPAQ-Short Form for daily physical activity assessment.

RESULTS: The Borg Dyspnoea Scale, maximum oxygen uptake, and resting oxygen saturation emerged as crucial indicators for predicting physical activity levels in post-COVID-19 individuals. Compared to these variables, resting and post-exercise heart rates were statistically insignificant.

CONCLUSION: Physical exertion and oxygen saturation are potentially crucial predictors of physical activity levels in individuals with persistent post-COVID-19 symptoms. These findings offer valuable insights for managing long COVID-19 syndrome, emphasising the need for tailored interventions to address reduced physical activity levels in affected individuals.

RevDate: 2025-05-07

Rovito R, Bono V, Coianiz N, et al (2025)

Multi-layered deep immune profiling, SARS-CoV-2 RNAemia and inflammation in unvaccinated COVID-19 individuals with persistent symptoms.

Communications medicine, 5(1):155.

BACKGROUND: Long-COVID immunopathogenesis involves diverse factors. We longitudinally characterize hospitalized COVID-19 patients, examining the role of SARS-CoV-2 RNAemia and inflammation in immune dysregulation.

METHODS: Hospitalized patients are evaluated during acute infection (T0), 3 months post-symptom onset (T1), and 3 years if symptoms persisted (T2). Immune profile includes characterization of SARS-CoV-2-specific/non-specific T/B cells (flow cytometry) and antibodies (ELISA, neutralization, ADCC). RNAemia and cytokines are quantified (RT-PCR, cytometric beads array) and correlated.

STATISTICS: non-parametric cross-sectional, longitudinal and correlation analyses.

RESULTS: Here we show 48 hospitalized individuals during acute COVID-19, 38 exhibit early persistent symptoms (EPS+) 3 months post-symptoms onset, 10 do not (EPS-). Groups are comparable for age, sex, co-morbidities. The EPS+ shows fatigue, dyspnoea, anosmia/dysgeusia, diarrhea, chronic pain, mnestic disorders. Over time, they show a reduction of neutralization ability and total SARS-CoV-2-specific CD4 T cells, with increased total CD4 TEMRA, and failure to increase RBD-specific B cells and IgA+ MBCs. EPS+ patients show higher levels of T0-IFN-γ + CD4 TEMRA, T1-IL-2 + CD4 TEM and T1-TNF-α + CD4 cTfh. In EPS+, baseline SARS-CoV-2 RNAemia positively correlates with CD4 TEMRA, follow-up SARS-CoV-2 RNAemia with ADCC. Among 38 EPS+ individuals at T1, 33 are evaluated 3 years after infection, 5 are lost at follow-up. 10/33 EPS+ show long-term symptoms (late persistent symptoms, EPS + LPS+), whereas 23/33 fully recover (EPS + LPS-). Antibodies, RNAemia, and cytokines show no differences between/within groups at any time point.

CONCLUSIONS: Early persistent symptoms are associated with multi-layered SARS-CoV-2-specific/non-SARS-CoV-2-specific immune dysregulation. The shift towards non-Ag-specific TEMRA and ADCC trigger in EPS+ may relate to SARS-CoV-2 RNAemia. Early immune dysregulation does not associate with long-term persistent symptoms. Further research on SARS-CoV-2 RNAemia and early immune dysregulation is needed.

RevDate: 2025-05-05

Vieira Junior JCA, Sander MRL, Matos JAO, et al (2025)

Neurological Post-Acute Sequelae of COVID-19 in Non-Hospitalized Patients: An Integrative Review.

Biological research for nursing [Epub ahead of print].

The COVID-19 pandemic has had a significant impact on the global population. The infection, caused by SARS-CoV-2, presents with a variety of clinical manifestations, from asymptomatic cases to more severe forms, including a variety of neurological symptoms, such as fatigue, weakness, brain fog, paresthesias, dysautonomia, anosmia, and dysgeusia. Additionally, the disease is associated with the long COVID syndrome, in which there is persistence of the effects and symptoms of the acute phase. In recent years the literature has shown relevant data on long COVID, but there is still a need to deepen the knowledge about these long term manifestations. Thus, the present study aimed to describe the main neurological sequelae resulting from SARS-CoV-2 infection in non-hospitalized population during the long phase of the disease, gathering scientific evidence through an integrative review of the prevalence of symptoms, patient profile, duration and severity of sequelae, risk factors, comorbidities, and possible nervous system structural damage. The PubMed/Medline database was used with descriptors and, at the end of the screening process with predefined inclusion and exclusion criteria, 22 studies were included. A group of neurological symptoms associated with long COVID was identified: myalgia, dysgeusia, memory alterations, olfactory dysfunction, dizziness, and pain. Most patients presented multiple symptoms that lasted for more than one year with a significant impact on quality of life. The main risk factors were dyslipidemia, age, ethnicity, muscle/ joint pain, and sex. This review highlights the importance of further studies on the syndrome, its etiology, diagnosis, follow-up, and treatments.

RevDate: 2025-05-07

Bui DP, Bast E, Trinh H, et al (2025)

Use of Long COVID Clinics in the Veterans Health Administration: Implications for the path forward.

Health affairs scholar, 3(5):qxaf080.

Long COVID is a serious chronic illness that can present in many forms and impact daily functioning and quality of life. Without curative treatments, management of long COVID requires coordination and ongoing access to multidisciplinary care. Starting in 2020, the Veterans Health Administration (VHA), established a national network of Long COVID Clinics (LCCs). In this retrospective cohort study of 494 547 veterans with documented SARS-CoV-2 infection in the VHA from March 2020 to April 2022 (n = 494 547), we examined trends in ICD-10 U09.9 diagnosis code use for long COVID and LCC use in the VHA up to May 2024. Overall, 5.9% (n = 29 195) of patients in our cohort had a documented U09.9 code and 2% had at least 1 LCC visit. Among veterans with a U09.9 code, 17.4% (n = 5089) used LCCs. LCC use rates were low across all patient subgroups. LCCs were more available to veterans residing in the South census region (28% vs <7% use rate) than veterans in other regions. Developing evidence about LCC effectiveness and ensuring equitable access to LCCs within and beyond the VHA will be critical in meeting the evolving needs of people with long COVID.

RevDate: 2025-05-07

Guzmán Rivera J, Zheng H, Richlin B, et al (2025)

Combining Mass Spectrometry with Machine Learning to Identify Novel Protein Signatures: The Example of Multisystem Inflammatory Syndrome in Children.

medRxiv : the preprint server for health sciences.

OBJECTIVES: We demonstrate an approach that integrates biomarker analysis with machine learning to identify protein signatures, using the example of SARS-CoV-2-induced Multisystem Inflammatory Syndrome in Children (MIS-C).

METHODS: We used plasma samples collected from subjects diagnosed with MIS-C and compared them first to controls with asymptomatic/mild SARS-CoV-2 infection and then to controls with pneumonia or Kawasaki disease. We used mass spectrometry to identify proteins. Support vector machine (SVM) algorithm-based classification schemes were used to analyze protein pathways. We assessed diagnostic accuracy using internal and external cross-validation.

RESULTS: Proteomic analysis of a training dataset containing MIS-C (N=17), and asymptomatic/mild SARS-CoV-2 infected control samples (N=20) identified 643 proteins, of which 101 were differentially expressed. Plasma proteins associated with inflammation and coagulation increased and those associated with lipid metabolism decreased in MIS-C relative to controls. The SVM machine learning algorithm identified a three-protein model (ORM1, AZGP1, SERPINA3) that achieved 90.0% specificity, 88.2% sensitivity, and 93.5% area under the curve (AUC) distinguishing MIS-C from controls in the training set. Performance was retained in the validation dataset utilizing MIS-C (N=17) and asymptomatic/mild SARS-CoV-2 infected control samples (N=10) (90.0% specificity, 84.2% sensitivity, 87.4% AUC). We next replicated our approach to compare MIS-C with similarly presenting syndromes, such as pneumonia (N=17) and Kawasaki Disease (N=13) and found a distinct three-protein signature (VWF, SERPINA3, and FCGBP) that accurately distinguished MIS-C from the other conditions (97.5% specificity, 89.5% sensitivity, 95.6% AUC). We also developed a software tool that may be used to evaluate other protein pathway signatures using our data.

CONCLUSIONS: We used MIS-C, a novel hyperinflammatory illness, to demonstrate that the use of mass spectrometry to identify candidate plasma proteins followed by machine learning, specifically SVM, is an efficient strategy for identifying and evaluating biomarker signatures for disease classification.

RevDate: 2025-05-05

Lucena Lage S, Bricker-Holt K, Rocco JM, et al (2025)

Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection.

medRxiv : the preprint server for health sciences.

SARS-CoV-2 can cause a variety of post-acute sequelae including Long COVID19 (LC), a complex, multisystem disease characterized by a broad range of symptoms including fatigue, cognitive impairment, and post-exertional malaise. The pathogenesis of LC is incompletely understood. In this study, we performed comprehensive cellular and transcriptional immunometabolic profiling within a cohort that included SARS-CoV-2-naïve controls (NC, N=30) and individuals with prior COVID-19 (∼4-months) who fully recovered (RC, N=38) or went on to experience Long COVID symptoms (N=58). Compared to the naïve controls, those with prior COVID-19 demonstrated profound metabolic and immune alterations at the proteomic, cellular, and epigenetic level. Specifically, there was an enrichment in immature monocytes with sustained inflammasome activation and oxidative stress, elevated arachidonic acid levels, decreased tryptophan, and variation in the frequency and phenotype of peripheral T-cells. Those with LC had increased CD8 T-cell senescence and a distinct transcriptional profile within CD4 and CD8 T-cells and monocytes by single cell RNA sequencing. Our findings support a profound and persistent immunometabolic dysfunction that follows SARS-CoV-2 which may form the pathophysiologic substrate for LC. Our findings suggest that trials of therapeutics that help restore immune and metabolic homeostasis may be warranted to prevent, reduce, or resolve LC symptoms.

RevDate: 2025-05-05

Zhang S, Jahanbani F, Chander V, et al (2025)

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.

medRxiv : the preprint server for health sciences pii:2025.04.15.25325899.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogeneous, and systemic disease defined by a suite of symptoms, including unexplained persistent fatigue, post-exertional malaise (PEM), cognitive impairment, myalgia, orthostatic intolerance, and unrefreshing sleep. The disease mechanism of ME/CFS is unknown, with no effective curative treatments. In this study, we present a multi-site ME/CFS whole-genome analysis, which is powered by a novel deep learning framework, HEAL2. We show that HEAL2 not only has predictive value for ME/CFS based on personal rare variants, but also links genetic risk to various ME/CFS-associated symptoms. Model interpretation of HEAL2 identifies 115 ME/CFS-risk genes that exhibit significant intolerance to loss-of-function (LoF) mutations. Transcriptome and network analyses highlight the functional importance of these genes across a wide range of tissues and cell types, including the central nervous system (CNS) and immune cells. Patient-derived multi-omics data implicate reduced expression of ME/CFS risk genes within ME/CFS patients, including in the plasma proteome, and the transcriptomes of B and T cells, especially cytotoxic CD4 T cells, supporting their disease relevance. Pan-phenotype analysis of ME/CFS genes further reveals the genetic correlation between ME/CFS and other complex diseases and traits, including depression and long COVID-19. Overall, HEAL2 provides a candidate genetic-based diagnostic tool for ME/CFS, and our findings contribute to a comprehensive understanding of the genetic, molecular, and cellular basis of ME/CFS, yielding novel insights into therapeutic targets. Our deep learning model also offers a potent, broadly applicable framework for parallel rare variant analysis and genetic prediction for other complex diseases and traits.

RevDate: 2025-05-06
CmpDate: 2025-05-05

Leggat F, Torrens-Burton A, Sewell B, et al (2025)

Personalisation at the Core of Success: Process Evaluation of the LISTEN Randomised Controlled Trial Evaluating a Personalised Self-Management Support Intervention for People Living With Long Covid.

Health expectations : an international journal of public participation in health care and health policy, 28(3):e70270.

BACKGROUND: The development and evaluation of rehabilitation interventions designed to support people with Long Covid (LC) remains an important ongoing priority. Many people with LC experience episodic, debilitating symptoms that can reduce their ability to engage in all areas of activity. The Long CovId personalised Self-managemenT support co-design and EvaluatioN (LISTEN) trial co-designed and evaluated a personalised self-management support intervention to build confidence and support people to live better with LC. This paper describes the context, implementation, mechanisms of impact and impacts from the LISTEN intervention, in comparison with usual LC services accessed within the National Health Service (NHS).

METHODS: A mixed methods process evaluation was nested within the LISTEN pragmatic, multi-site, randomised controlled trial. Data were collected from sites in England and Wales between September 2022 and January 2024. Observations and focus groups with healthcare practitioners (HCPs) delivering the intervention were conducted to assess fidelity. Standardised implementation measures, focussed on intervention feasibility, acceptability and appropriateness, were gathered from HCPs and intervention participants. Semi-structured interviews were undertaken with a subset of participants across both trial arms. Data were analysed independently using descriptive statistics, or reflexive thematic analyses, and subsequently integrated, drawing upon the Consolidated Framework for Implementation Research v2.

FINDINGS: Thirty-six HCPs participated in the process evaluation, and 197 intervention participants completed standardised implementation measures. Across both trial arms, 49 participants took part in semi-structured interviews. Six integrated themes were constructed from all data sources describing and illustrating links between the context, implementation, mechanisms of impact and impacts: 'Delivery during uncertainty and ambiguity', 'Diversity and consistency of usual care', 'Drivers for self-care and the impact of self-generated expertise', 'Appropriate if unexpected support', 'Personalisation at the core of success' and 'A spectrum of change'.

CONCLUSION: The LISTEN intervention is an appropriate, feasible intervention for participants and HCPs. The intervention can be delivered to a high level of fidelity following training and with ongoing HCP support. Access, receipt and perceptions of NHS LC services were variable. Personalised, relational interventions, such as LISTEN, can foster favourable impacts on confidence, knowledge and activity and are acceptable and strongly recommended within LC rehabilitation services.

The study was supported by a patient and public involvement and engagement (PPIE) group from project conception to study end. Using their lived expertise, seven people with LC supported accessible recruitment (e.g., materials), data collection (e.g., topic guides), data interpretation (e.g., theme construction and reviewing findings) and dissemination activities (e.g., online webinars).

TRIAL REGISTRATION: ISRCTN36407216, registered 27/01/2022.

RevDate: 2025-05-03

Samanci B, Ay U, Gezegen H, et al (2025)

Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection.

Cortex; a journal devoted to the study of the nervous system and behavior, 187:98-110 pii:S0010-9452(25)00101-7 [Epub ahead of print].

This study aimed to investigate the neurocognitive deficits, structural brain alterations, and network abnormalities in individuals who had a mild SARS-CoV-2 infection, with and without brain fog, as a symptom of long COVID. A cross-sectional study was conducted involving 75 participants, categorized into three groups: 24 healthy controls (HCs), 26 COVID-19 survivors without brain fog (woFOG), and 25 with brain fog (wFOG). Neuropsychological assessments included the Free and Cued Selective Reminding Test (FCSRT) and Addenbrooke's Cognitive Examination-Revised (ACE-R). Structural and functional brain alterations were examined using voxel-based morphometry (VBM) and resting-state functional MRI (rs-fMRI). The wFOG group exhibited significant cognitive impairments, particularly in delayed free recall, attention, memory, and visuospatial skills, compared to both the woFOG and HC groups. Structural MRI analyses revealed reduced gray matter concentrations (GMC) in the left inferior temporal gyrus, left fusiform gyrus, and right orbital gyri in both COVID-19 groups relative to HCs. Additionally, the wFOG group exhibited further GMC reductions in the bilateral caudate nuclei, right putamen/pallidum, and amygdala compared to the woFOG group. rs-fMRI analyses demonstrated altered connectivity patterns in COVID-19 survivors, characterized by increased connectivity in the default mode network and visual networks, alongside decreased connectivity in the dorsal attention network. These findings indicate that even mild COVID-19 can result in persistent neurocognitive deficits, structural brain alterations, and functional network abnormalities, both in individuals with and without brain fog. The observed changes highlight the importance of long-term monitoring and targeted interventions to address potential cognitive and neurological consequences of long COVID.

RevDate: 2025-05-05
CmpDate: 2025-05-03

Louvrier M, Saussez S, JR Lechien (2025)

Psychological Distress in Patients with Long-lasting COVID-19 Olfactory Dysfunction.

Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale, 54:19160216251328960.

ObjectiveThe aim of this study was to investigate the psychological distress associated with long-lasting COVID-19 olfactory dysfunction (OD).MethodsPatients with an OD lasting for more than 6 months were consecutively recruited from the Dour Medical Center (Belgium) from August 2023 to January 2024. The olfaction was investigated with the Olfactory Disorder Questionnaires (ODQ) and the threshold, identification, and discrimination (TDI) testing. General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) were used to investigate the psychological distress of patients. The olfactory and psychological outcomes of patients were compared with a group of individuals without OD.ResultsA total of 220 patients and 102 asymptomatic individuals completed the evaluations. The mean duration of OD was 31.1 ± 25.1 months. The mean GAD-7 and PHQ-9 scores were significantly higher in OD patients than in asymptomatic individuals (P < 0.008). The OD patient prevalence of mild-to-severe depression (51.2% vs. 44.1%) and mild-to-severe anxiety (39.5% vs. 32.4%) disorders was significantly higher than asymptomatic individuals. Severe anxiety was associated with the presence of anosmia. GAD-7 and PHQ-9 scores were higher in females than in males. The severity of depression (PHQ-9) and anxiety (GAD-7) was significantly associated with the severity of OD (ODQ) and nasal symptoms (SNOT-22).ConclusionThe presence of a long-lasting OD in patients consulting in otolaryngology is associated with psychological distress. While the causality relationship remains unclear, depression and anxiety symptoms must be investigated in this subgroup of patients with long COVID-19.

RevDate: 2025-05-05

Hausmann E (2025)

Books: The Age of Diagnosis: Sickness, Health and Why Medicine Has Gone Too Far: The curious characterisation of long COVID as a psychosomatic condition.

The British journal of general practice : the journal of the Royal College of General Practitioners, 75(754):228-229 pii:75/754/228.

RevDate: 2025-05-06
CmpDate: 2025-05-06

Barlattani T, Celenza G, Cavatassi A, et al (2025)

Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.

Current neuropharmacology, 23(6):686-704.

COVID-19 is associated with neuropsychiatric symptoms, such as anosmia, anxiety, depression, stress-related reactions, and psychoses. The illness can cause persistent cognitive impairment and "brain fog", suggesting chronic brain involvement. Clinical entities of ongoing symptomatic COVID-19 and Post COVID Syndrome (PCS) mainly present neuropsychiatric symptoms such as dysgeusia, headache, fatigue, anxiety, depression, sleep disturbances, and post-traumatic stress disorder. The pathophysiology of COVID-19-related brain damage is unclear, but it is linked to various mechanisms such as inflammation, oxidative stress, immune dysregulation, impaired glutamate homeostasis, glial and glymphatic damage, and hippocampal degeneration. Noteworthy is that the metabotropic receptor mGluR2 was discovered as a mechanism of internalisation of SARS-CoV-2 in Central Nervous System (CNS) cells. N-acetylcysteine (NAC) and acetyl-L-carnitine (ALC) are two supplements that have already been found effective in treating psychiatric conditions. Furthermore, NAC showed evidence in relieving cognitive symptomatology in PCS, and ALC was found effective in treating depressive symptomatology of PCS. The overlapping effects on the glutamatergic system of ALC and NAC could help treat COVID-19 psychiatric symptoms and PCS, acting through different mechanisms on the xc-mGluR2 network, with potentially synergistic effects on chronic pain and neuro-astrocyte protection. This paper aims to summarise the current evidence on the potential therapeutic role of NAC and ALC, providing an overview of the underlying molecular mechanisms and pathophysiology. It proposes a pathophysiological model explaining the effectiveness of NAC and ALC in treating COVID-19-related neuropsychiatric symptoms.

RevDate: 2025-05-02

van Leeuwen LPM, Van Coillie S, Prévot J, et al (2025)

LONG TERM EFFECTS OF COVID-19 IN PRIMARY IMMUNODEFICIENCY PATIENTS: AN IPOPI WORLDWIDE SURVEY.

The Journal of allergy and clinical immunology pii:S0091-6749(25)00497-X [Epub ahead of print].

BACKGROUND: During the COVID-19 pandemic, many individuals developed persistent symptoms after COVID-19. There is limited data on these long-term effects in the primary immunodeficiency (PID) community.

OBJECTIVE: This study aimed to understand long-term symptoms post-COVID-19 in PID patients, focusing on prevalence, risk factors, viral persistence and the impact of COVID-19 on their health-related quality of life (HR-QoL).

METHODS: A global, multilingual web-based survey was conducted by the International Patient Organisation for Primary Immunodeficiencies (IPOPI) between July and October 2023. Self-reported data on demographics, PID diagnosis, comorbidities, COVID-19, and HR-QoL (EQ-5D-5L) were collected and analyzed.

RESULTS: Among 1,160 respondents, 25% reported persistent symptoms post-COVID-19. Common symptoms included fatigue, headache, and nasal symptoms. These respondents reported a significantly higher prevalence of symptoms across all categories-systemic, pain, cardiopulmonary, gastrointestinal, neurological, psychological, neurocognitive, and others-except upper respiratory tract symptoms, compared to those without persistent symptoms. Independent risk factors for developing persistent symptoms included female sex, asthma, neurological diseases, and predominantly antibody deficiency other than common variable immunodeficiency (CVID) or agammaglobulinemia. Viral clearance was not achieved within one month in 30% of patients with persistent symptoms. HR-QoL declined during the pandemic across all PID categories, even in those without COVID-19, but especially in those with a symptom duration over six months.

CONCLUSION: Persistent symptoms post-COVID-19 are prevalent among PID patients, with various risk factors identified. The COVID-19 pandemic had a considerable impact on the HR-QoL of PID patients, regardless of COVID-19 status.

RevDate: 2025-05-02

Butzin-Dozier Z, Ji Y, Wang LC, et al (2025)

COVID-19 Vaccination Timing, Relative to Acute COVID-19, and Subsequent Risk of Long COVID.

medRxiv : the preprint server for health sciences pii:2025.04.22.25326224.

OBJECTIVES: Long COVID is a debilitating condition that impacts millions of Americans, but patients and clinicians have little information on how to prevent this disorder. Vaccination is a vital tool in preventing acute COVID-19 and may confer additional protection against Long COVID. There is limited evidence regarding the optimal timing of COVID-19 vaccination (i.e., vaccination schedule) to minimize the risk of Long COVID.

METHODS: We applied Longitudinal Targeted Maximum Likelihood Estimation to electronic health record (EHR) data from a retrospective cohort of patients vaccinated against COVID-19 between December 2021 and September 2022. We evaluated the association between binary COVID-19 vaccination status (two or more doses vs. zero doses) and 12-month Long COVID risk among patients diagnosed with acute COVID-19 between December 2021 and September 2022. In addition, we compared the 12-month cumulative risk of Long COVID (ICD-10 code U09.9) among patients diagnosed with acute COVID-19 one to three months after vaccination, three to five months after vaccination, or five to seven months after vaccination while adjusting for relevant high-dimensional baseline and time-dependent covariates.

RESULTS: We analyzed EHR data from a retrospective cohort of 1,558,018 patients. In our binary cohort (n = 519,980), we found that vaccinated patients had a lower risk of Long COVID than unvaccinated patients (adjusted marginal risk ratio 0.84 (0.81, 0.88)). In our longitudinal cohort (n = 1,085,291), we did not find a significant difference in Long COVID risk comparing patients who were diagnosed with acute COVID-19 one to three months after vaccination versus patients who were diagnosed with COVID-19 three to five months (adjusted marginal risk ratio 0.93 (95% CI 0.62, 1.41) or 5 to 7 months (adjusted marginal risk ratio 1.06 (95% CI 0.72, 1.56)) after vaccination.

CONCLUSIONS: We found that COVID-19 vaccination before SARS-CoV-2 infection was protective against Long COVID, and we did not find that this protection significantly waned within 7 months after vaccination. These findings suggest that COVID-19 vaccination protects against Long COVID.

RevDate: 2025-05-02

Nakagawa F, Palich R, Kall M, et al (2025)

Impact of COVID-19 and factors associated with long COVID and COVID-19 vaccine uptake in people with HIV in the United Kingdom: Results from Positive Voices 2022.

HIV medicine [Epub ahead of print].

OBJECTIVES: We assessed the impact of COVID-19, and the prevalence and factors associated with a history of COVID-19 infection, long COVID and incomplete COVID-19 vaccine uptake among people with HIV.

METHODS: Positive Voices 2022 is a questionnaire study of people accessing HIV care in the United Kingdom (March 2022-April 2023). Logistic regression assessed factors associated with a history of COVID-19 (previous positive test), long COVID among those with a history of COVID-19 (ongoing symptoms, with COVID-19 onset >3 months previously) and incomplete COVID-19 vaccine uptake (less than three doses of vaccine), adjusted for: age; gender; ethnicity; and year of HIV diagnosis.

RESULTS: In all, 4188 participants were included. Commonly reported negative impacts of the pandemic were on social contact (44% of participants), mental health (30%), healthcare access (26%) and financial security (25%). Overall, 2068 of 4188 (49.4%) participants had a history of COVID-19. Of these, 10.8% met criteria for long COVID, associated with female gender, unemployment, financial hardship, earlier HIV diagnosis date, diabetes diagnosis, asthma/chronic obstructive pulmonary disease diagnosis, obesity and symptoms of depression and anxiety. Overall, 95.8% reported having at least one vaccine dose, but 649 (15.7%) participants had incomplete vaccine uptake, associated with younger age, female gender, Black African ethnicity, lower education, financial hardship, unemployment, multioccupancy household, more recent HIV diagnosis, detectable HIV viral load and symptoms of depression and anxiety.

CONCLUSIONS: About half of participants had a history of COVID-19, of whom 11% had persistent symptoms (long COVID). COVID-19 vaccine uptake was high, but incomplete uptake was apparent for 16% of participants and was more common among women, younger people, Black African individuals and those with socio-economic disadvantage.

RevDate: 2025-05-04

Simonetti A, Bardi F, Margoni S, et al (2025)

Affective temperament modulates the relationship between physical and psychiatric symptoms during long-COVID: results from the Gemelli against COVID-19 post-acute care service.

Journal of affective disorders, 383:315-322 pii:S0165-0327(25)00743-8 [Epub ahead of print].

BACKGROUND: Affective temperaments represent the substrate of personality that can influence the expression of chronic infectious diseases, including COVID-19 and its sequelae. However, research conducted so far on this topic focused on narrow aspects of psychopathology.

AIM: To investigate the effect of affective temperaments on the relationship between physical and psychiatric symptoms in patients with long-COVID.

METHODS: The sample consisted of 1513 patients who have been hospitalized for COVID-19 and developed long-COVID. Participants performed a multidisciplinary assessment including psychiatric evaluation through the administration of rating scales. The psychiatric dimensions assessed included severity of depressive, anxiety, manic symptoms, anhedonia, hopelessness, suicidal risk, psychological distress, levels of well-being, resilience, emotion regulation, and levels of post-traumatic stress disorder (PTSD). Affective temperament was assessed through the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire (TEMPS-A). We used TEMPS-A subscales as moderators and sociodemographic and COVID-19/long-COVID-related clinical characteristics as predictors. Psychiatric rating scales total scores were outcome variables.

RESULTS: Cyclothymic, irritable, and depressive temperaments strengthened the relationship between number of long-COVID symptoms, levels of anhedonia and poor psychological well-being. Cyclothymic and irritable temperaments weakened the relationship between number of long-COVID symptoms and history of intensive care unit admission and PTSD severity. Depressive temperament strengthened the latter relationship.

LIMITATION: The clinical variables included in the analyses do not represent the entire range of psychopathology.

CONCLUSIONS: Depressive temperament enhanced the relationship between physical and psychiatric symptoms in patients with long-COVID, whereas the effects of cyclothymic and irritable temperaments may depend on the psychiatric dimension assessed.

RevDate: 2025-05-01
CmpDate: 2025-05-01

Bontempo AC, Bontempo JM, PR Duberstein (2025)

Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research.

Psychological bulletin, 151(4):399-427.

The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients' symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients' psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan's (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person's experiences with illness. We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia. Consistent with Linehan's theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay. Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

RevDate: 2025-05-01

Uswatte G, Taub E, Ball K, et al (2025)

Long COVID brain fog treatment: An early-phase randomized controlled trial of constraint-induced cognitive therapy signals go.

Rehabilitation psychology pii:2026-10155-001 [Epub ahead of print].

PURPOSE: Long COVID brain fog is often disabling. Yet, no empirically supported treatments exist. This study's objectives were to evaluate the feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

DESIGN: Sixteen community residents ≥3 months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment as usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive training program. CICT was deemed feasible if (a) ≥ 80% of participants were adherent, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) < 2 study-related, serious adverse events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

RESULTS: Fourteen completed Immediate-CICT (n = 7) or TAU (n = 7); two withdrew from TAU before their second testing session. Completers were, M (SD): 10 (7) months post-COVID; 51 (13) years old; 10 females, four males; one African American, and 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M = 3.7 points, p < .001, d = 2.6) and brain fog (M = -4 points, p < .001, d = -2.9). Four of five nonretired Immediate-CICT participants returned to work posttreatment; no TAU participants did, p = .048.

CONCLUSION: Those who received CICT adhered to the protocol and were highly satisfied with their outcomes. The findings warrant a large-scale randomized controlled trial with an active-comparison group. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

RevDate: 2025-05-01

Ni ZC, Lv L, Xu JT, et al (2025)

Clinical characterization of long COVID among Chinese healthcare workers: a multicenter, cross-sectional study: Long COVID in Chinese healthcare workers.

Journal of occupational and environmental medicine pii:00043764-990000000-00840 [Epub ahead of print].

OBJECTIVES: Since the outbreak of COVID-19, the pandemic has profoundly affected global health and socio-economic systems. Many recovered patients continue to experience "long COVID" symptoms, affecting their daily life and work performance.

METHODS: We utilized questionnaires to investigate long COVID symptoms among healthcare workers and their impact on daily life and work.

RESULTS: Of the healthcare workers, 17% reported long COVID symptoms. Among these, 64.6% experienced neurological symptoms, 57.3% had psychological symptoms, 43% exhibited respiratory symptoms, 44.4% demonstrated cardiovascular symptoms, 58.8% had musculoskeletal symptoms, 31.8% presented with skin symptoms, 31.8% had endocrine symptoms, 34.3% had digestive symptoms, and 70.7% reported general symptoms.

CONCLUSIONS: Our study reveals that 17% of healthcare workers experience long COVID, with neurological and psychological symptoms being particularly prominent, significantly impacting their daily life and work.

RevDate: 2025-05-02

Cozma A, Briciu V, Sitar-Tăut AV, et al (2025)

Cardiac Dysfunction and Subclinical Atherosclerosis in Post-COVID-19 Patients.

Cardiac failure review, 11:e09.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is still a burden for healthcare systems worldwide. Now, the focus is not only on acute infections, but also on the long-term effects of COVID-19. The present study aimed to evaluate the impact of SARS-CoV-2 infection on the cardiovascular system, and determine the evolution of these changes over 6 months in patients with mild and moderate COVID-19.

METHODS: The prospective observational study included 103 patients with mild and moderate COVID-19. The patients underwent an echocardiography and a measurement of the arterial stiffness parameters at baseline and 6 months from the initial assessment.

RESULTS: The diastolic dysfunction (the left atrium volume) was statistically significant at baseline and at the 6-month follow-up in men with moderate COVID-19. The ejection fraction presented significant differences globally in mild versus moderate COVID-19 (p=0.043) that disappeared at 6-month follow-up. Global longitudinal strain alterations were also found in both mild and moderate COVID-19 cases. Regarding the aortic pulse wave velocity, the SARS-CoV-2 infection did not influence the arterial stiffness. Ventricular arterial coupling was significantly altered in moderate COVID-19 at the 6-month evaluation (p=0.0218). Male patients presented a lower tricuspid annular plane systolic excursion at baseline. Right ventricular systolic dysfunction was more frequent among men. Systolic pulmonary arterial pressure increased significantly only in men with moderate disease. Additionally, statistically significant changes at baseline and at 6 months were found regarding the intima-media thickness.

CONCLUSION: This study shows the cardiovascular long-term sequelae associated with COVID-19 in mild and moderate cases, and emphasises the appropriate investigations for their diagnosis and follow-up.

RevDate: 2025-05-02

Williams JE, Kim Y, J Moramarco (2025)

Research Supports the Integration of Acupuncture in Mainstream Health Care for the Management of Chronic Diseases.

Medical acupuncture, 37(2):106-111.

PURPOSE: To address the role of acupuncture in mainstream health care for symptom relief, condition outcome, pain management, and shared therapy in resolving chronic diseases. This article explores how acupuncture education can adapt to meet the standards required for inclusion in conventional health care.

OBJECTIVES: To discuss the future of acupuncture education and its part in training providers for inclusion in a comprehensive health care system that involves physician acupuncturists and licensed acupuncturists for treating and managing specific chronic diseases. To strategize the future of acupuncture education at an advanced clinical level that fosters incorporating acupuncture therapy into selected allopathic settings. To encourage the recognition of translational research for promoting the acceptance of acupuncture by providers and insurers.

CONCLUSION: Translational research employs clinical evidence to support acupuncture therapy when incorporated into selected areas of allopathic practices, including pain management, palliative care for patients with end-stage cancer, sleep disorders, anxiety disorders, post-traumatic stress, female hormonal conditions such as premenstrual syndrome and menopausal syndrome, as well as chronic fatigue syndromes including Myalgic encephalomyeltitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Advanced clinical training in acupuncture schools and postgraduate certification courses are required to prepare acupuncturists to safely and effectively provide the specialized integrative acupuncture services needed in these clinical areas.

RevDate: 2025-05-02

Wang S, Salway RJ, Nicklay M, et al (2025)

Effectiveness of Dual Sympathetic Blocks for Sympathetically Mediated Symptoms in Post-acute Sequelae of SARS-CoV-2 (PASC): An Open-Label, Non-randomized Pilot Study.

Cureus, 17(3):e81530.

BACKGROUND: Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, is a multi-system disorder often involving dysautonomia and pain, linked to persistent sympathetic nervous system hyperactivity. Dual sympathetic blocks (DSBs), including stellate ganglion blocks (SGBs), are minimally invasive procedures that may recalibrate dysregulated sympathetic signaling and alleviate PASC symptoms.

METHODS: This open-label, non-randomized pilot study included 20 participants with PASC experiencing pain and autonomic symptoms. Participants received right-sided and left-sided SGB procedures one week apart. Symptoms were assessed at baseline, week one, and week four using the Composite Autonomic Symptom Score (COMPASS-31) and Patient-Reported Outcomes Measurement Information System (PROMIS-29) scales.

RESULTS: Seventeen participants completed the study, demonstrating significant improvements in autonomic dysfunction (38.4% reduction in COMPASS-31 scores, p = 0.0016) and pain interference (48.4% reduction, p < 0.001) by week four. Improvements in sleep quality and fatigue were also significant by week four (p = 0.016 and p = 0.049, respectively). Overall, 88.2% of participants reported symptom relief, and no adverse events were observed.

CONCLUSIONS: DSBs appear to be a promising intervention for PASC-related dysautonomia and pain. These findings warrant further investigation in larger, randomized controlled trials to confirm efficacy and explore the underlying mechanisms.

RevDate: 2025-05-01

Thant TM, Khandai AC, Gillan A, et al (2025)

Neuropsychiatric Symptoms of Subacute and Chronic Long COVID.

The American journal of psychiatry, 182(5):498-499.

RevDate: 2025-05-02
CmpDate: 2025-05-01

Gao Y, Cai C, Adamo S, et al (2025)

Identification of soluble biomarkers that associate with distinct manifestations of long COVID.

Nature immunology, 26(5):692-705.

Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8[+] T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.

RevDate: 2025-04-30

Harker JA, RS Thwaites (2025)

Unravelling the interplay between respiratory disease and the immune landscape in long COVID.

Nature immunology, 26(5):640-641.

RevDate: 2025-04-30

Trivieri MG, Devesa A, Robson PM, et al (2025)

Prevalence of Persistent Cardiovascular and Pulmonary Abnormalities on PET/MRI and DECT Imaging in Long COVID Patients.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine pii:jnumed.124.268980 [Epub ahead of print].

The objective of this study is to describe the prevalence of inflammatory cardiopulmonary findings in a prospective cohort of long coronavirus disease (LC) patients. Methods: Subjects with a history of coronavirus disease 2019 infection, persistent cardiopulmonary symptoms 9-12 mo after initial infection, and a clinical assessment compatible with LC underwent cardiopulmonary [18]F-FDG PET/MRI, dual-energy CT (DECT) of the lungs, and plasma protein analysis (subgroup). A control group that included subjects with a history of acute severe acute respiratory syndrome coronavirus 2 infection but without cardiopulmonary symptoms at recruitment was also characterized. Results: Ninety-eight patients (median age, 48.5 y; 47% men) were enrolled. The most common LC symptom was shortness of breath (80%), and 27% of participants were hospitalized. Of the subjects, 90% presented abnormalities in DECT, with 67% and 59% of participants demonstrating pulmonary infiltrates and abnormal perfusion, respectively. PET/MRI was abnormal for 57% of subjects: 24% showed cardiac involvement suggestive of myocarditis, 22% presented uptake reminiscent of pericarditis, 11% showed periannular uptake, and 30% showed vascular uptake (aortic or pulmonary). There was no myocardial, pericardial, periannular, or pulmonary uptake on the PET/MRI scans of the control group (n = 9). Analysis of plasma protein concentrations showed significant differences between the LC and the control groups. Lastly, the plasma protein profile was significantly different among LC patients with abnormal and normal PET/MRI. Conclusion: In LC subjects evaluated up to a year after coronavirus disease 2019 infection, our results indicate a high prevalence of abnormalities on PET/MRI and DECT, as well as significant differences in the peripheral biomarker profile, which might warrant further monitoring to exclude the development of complications such as pulmonary hypertension and valvular disease.

RevDate: 2025-04-30

Vacharathit V, Pluempreecha M, Manopwisedjaroen S, et al (2025)

Persistent IP-10/CXCL10 dysregulation following mild omicron breakthrough infection: Immune network signatures across COVID-19 waves and implications for mRNA vaccine outcomes.

Clinical immunology (Orlando, Fla.) pii:S1521-6616(25)00082-8 [Epub ahead of print].

This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. Samples from 114 mild COVID-19 patients across multiple waves were analyzed at three timepoints (T1: 2-4 weeks, T2: 3-4 months, T3: 6-8 months post-infection). Persistent IP-10 elevation up to 8 months suggests prolonged low-grade immune activation. Hybrid immunity from Omicron breakthrough infections provided broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.

RevDate: 2025-04-30

Aracena KA, Nwankwo GC, Lee CT, et al (2025)

Transcriptomic Profiling of Long COVID in Interstitial Lung Disease Patients Reveals Dysregulation of Mitochondrial Oxidative Phosphorylation.

American journal of respiratory cell and molecular biology [Epub ahead of print].

RevDate: 2025-05-01
CmpDate: 2025-04-30

Wang R, Lin M, Yu S, et al (2025)

Predictors of post-COVID-19 syndrome: a meta-analysis.

Journal of infection in developing countries, 19(4):490-497.

INTRODUCTION: Post Coronavirus Disease 2019 (COVID-19) Syndrome also known as long COVID-19 would affect survivors of various patients. At present, the evidence for predicting a poor prognosis of COVID-19 remains insufficient. This study aims to explore potential predictors of post-COVID-19 syndrome.

METHODOLOGY: A systematic review process and meta-analysis method are applied to identify the predictors. Systematic searches were conducted without language restrictions from December 1, 2019, to February 28, 2022, on PubMed, Embase, Google Scholar, Web of Science, and Cochrane Library using specific keywords relevant to our targets. The Newcastle Ottawa Scale observational research tool was used to assess study quality and the R (4.1.1) package meta was used for statistical analysis.

RESULTS: Our meta-analysis of 14 studies showed that females (OR = 1.42, 95% CI: 1.19-1.70), the severity of patients (OR = 2.43, 95% CI: 1.26-4.68), comorbidity (OR = 2.08, 95% CI: 1.29-3.35), dyspnea (OR = 2.02, 95% CI: 1.34-3.04) associated with a higher risk of post-COVID-19 syndrome.

CONCLUSIONS: Our study showed that females, the severity of COVID-19, comorbidity, and dyspnea were associated with a higher risk of post-COVID-19 syndrome. More attention should be paid to these factors to prevent and treat post-COVID-19 syndrome.

RevDate: 2025-04-30
CmpDate: 2025-04-30

Millhouse PW, Bloom RW, Beckstrand JN, et al (2025)

The Ganglia of the Head and Neck: Clinical Relevance for the Interventional Pain Physician.

Current pain and headache reports, 29(1):80.

PURPOSE OF REVIEW: The purpose of this article is to provide a comprehensive review of the ganglia of the head and neck and their role in the interventional management of chronic headaches and facial pain disorders.

RECENT FINDINGS: Interventions targeting the sphenopalatine, stellate and gasserian ganglia are well described in the literature for headaches and facial pain disorders. There is a growing body of evidence supporting use of these techniques for clinical conditions outside of pain such as post-traumatic stress disorder and Long COVID symptoms. These findings increase the potential applications of such procedures, making them more relevant to the interventional physician tasked with managing symptoms in difficult to treat medical conditions. Nerve blocks of the head and neck are used for diagnostic and therapeutic purposes in the management of headaches and facial pain disorders. Headaches, whether acute or chronic, are common pain conditions with a wide-range of etiologies and are often difficult to treat. Chronic facial pain can have a variety of underlying causes, including direct or indirect nerve damage, infection, inflammation, and muscle dysfunction. Traditional pain management strategies such as medications and physical therapy often fail or are associated with significant adverse effects. Interventions such as nerve blocks and neuroablative procedures have shown promise in managing headaches and facial pain by directly targeting the underlying causes. This review article summarizes the most recent evidence regarding the efficacy, safety, applications and limitations of these interventional pain management techniques.

RevDate: 2025-04-30

Kulik Née Ditzenberger GL, Zheng T, Jolley SE, et al (2025)

Physical Function Differences by COVID-19 Status: A Cross-Sectional Analysis from the RECOVER Adult Cohort.

Physical therapy pii:8122275 [Epub ahead of print].

IMPORTANCE: Many adults with prior SARS-CoV-2 infection have persistent limitations, but few studies have examined objective physical function impairment that persist longer than 3 months after infection.

OBJECTIVE: The objective was to characterize physical function impairment among adults with and without SARS-CoV-2 infection.

DESIGN: This study was a retrospective, cross-sectional analysis.

SETTING: Researching COVID to Enhance Recovery (RECOVER) initiative, a multi-site observational study in the United States (ClinicalTrials.gov: NCT05172024).

PARTICIPANTS: Participants were adults ≥18 years old with and without SARS-CoV-2 infection.

EXPOSURES: Groups were defined based on COVID-19 status at enrollment: never diagnosed (control), diagnosed with COVID-19 ≤ 12 weeks (recent COVID-19), or > 12 weeks prior to enrollment (remote COVID-19). The RECOVER-Adult Long COVID Index was used to further characterize by Index ≥12 versus 0.

MAIN OUTCOMES/MEASURES: Physical function (main outcome) was assessed by number of repetitions on a 30-second sit-to-stand test (30STS).

RESULTS: 30STS assessments at enrollment were available from 11,578 participants. 30STS repetitions were lowest in the remote COVID-19 group (n = 4942) with 11.5 (SD = 4.2) repetitions compared to 12.5 (SD = 4.7) repetitions among controls (n = 1887) or 12.2 (SD = 4.5) in recent COVID-19 (n = 4698). Remote COVID-19, but not recent COVID-19, was associated with lower physical function in the adjusted model (-0.61 repetitions; SD = 0.21). Those with RECOVER Long COVID Research Index ≥12 performed 1.6 (SD = 0.2) fewer repetitions than those with an Index equal 0.

CONCLUSIONS: Physical function impairment did not show clinically meaningful group differences between RECOVER Adult Cohort participants by COVID-19 status, or by Long COVID Index. Individual responses over time or in response to an intervention may be more clinically relevant.

RELEVANCE: In the RECOVER adult cohort, overall physical function differences by time since COVID-19 or by Long COVID Index were small. Individualized assessments are needed to determine functional impairment following COVID-19 diagnosis and subsequent steps for rehabilitation interventions.

RevDate: 2025-04-29
CmpDate: 2025-04-30

Santoro A, Bai F, Greco MF, et al (2025)

Short and long-term trajectories of the post COVID-19 condition: Results from the EuCARE POSTCOVID study.

BMC infectious diseases, 25(1):625.

BACKGROUND: Post COVID-19 condition (PCC) affects 10-40% of patients and is characterized by persisting symptoms at ≥ 4 weeks after SARS-CoV-2 infection. Symptoms can last 7 or even more months. How long PCC persists and any changes in its clinical phenotypes over time require further investigation. We investigated PCC trajectories and factors associated with PCC persistence.

MATERIAL AND METHODS: We included both hospitalized COVID-19 patients and outpatients from February 2020 to June 2023, who underwent at least one follow-up visit after acute infection at San Paolo Hospital, University of Milan. Follow-up visits were conducted at the post COVID-19 clinic or via telemedicine. During each follow-up examination, patients completed a short version of the World Health Organization (WHO) Case Report Form (CRF) for ongoing symptoms, the Hospital Anxiety and Depression Scale (HADS), and a screening tool for Post-Traumatic Stress Disorder (PTSD). Statistical analyses involved Chi-square, Mann-Whitney, Kruskal-Wallis tests, and logistic regression analysis.

RESULTS: We enrolled 853 patients (median age 62, IQR 52-73; 41% females). 551/853 (64.6%), 152/418 (36.4%) and 21/69 (30.4%) presented PCC at median follow up of 3 (IQR 2-3), 7 (IQR 6-10) and 26 (IQR 20-33) months, respectively (p < 0.001). The main clinical phenotypes were fatigue, respiratory sequelae, brain fog and chronic pain; anosmia/dysgeusia was observed mostly in the first post-acute period. Female sex, acute disease in 2020, a longer hospital stay and no COVID-19 vaccination were associated with persistence or resolution of PCC compared to never having had PCC. Anxiety, depression and PTSD were more common in PCC patients. By fitting a logistic regression analysis, acute infection in 2020 remained independently associated with persistent PCC, adjusting for age, sex, preexisting comorbidities and disease severity (AOR 0.479 for 2021 vs 2020, 95%CI 0.253-0.908, p = 0.024; AOR 0.771 for 2022 vs 2020, 95%CI 0.259-2.297, p = 0.641; AOR 0.086 for 2023 vs 2020, 95%CI 0.086-3.830, p = 0.565).

CONCLUSIONS: There was a reduction in the PCC burden 7 months following the acute phase; still, one third of patients experienced long-lasting symptoms. The main clinical presentations of PCC remain fatigue, respiratory symptoms, brain fog, and chronic pain. Having had SARS-CoV-2 infection during the first pandemic phases appears to be associated with persistent PCC.

RevDate: 2025-04-29
CmpDate: 2025-04-30

Kamdem OL, Dupre C, Heugno V, et al (2025)

SPACO+: a mixed methods protocol to assessing the effectiveness of an educative intervention in patients with Long Covid.

BMC infectious diseases, 25(1):623.

BACKGROUND: The management of many chronic diseases requires a multidisciplinary and holistic approach. Long Covid is a recent, poorly understood disease with several symptoms. Most recommendations suggest a multidisciplinary approach. While there are a few programs aimed to the management of Long Covid, to our knowledge very few were assessed. The SPACO + study therefore aims to evaluate an innovative program which combines the methods used in therapeutic education and in personalized multifactorial intervention for management of Long Covid. Here, we present the protocol of our study, which aims to evaluate the effectiveness of an educational intervention in terms of changes in quality of life at 6 months in comparison with standard clinical practice in patients suffering from Long Covid.

METHODS: To achieve our objectives, we have planned to carry out a prospective, multicentre, two-arm randomized controlled trial with a convergent parallel mixed methods design. Two countries are involved in this study: France and Cameroon. The study concerns patients aged 18 and over, who have been infected with Covid-19. They must also be diagnosed as having Long Covid in accordance with the WHO definition. The number of subjects required for the study is 400 individuals. Participants will be randomly assigned to either the intervention or control group using a dynamic randomization process to ensure balanced group characteristics. The SPACO + program is an educative intervention with individual follow-up by a nurse dedicated to the program. The SPACO + program offers five workshops, two of which are compulsories. Patients take part in the other workshops according to their needs. The program includes an 8 - 10 weeks intervention period. Each session lasts two hours and includes breaks (pacing). The main outcome measure will be quality of life, evaluated through the SF-36. Primary and secondary outcomes, with few exceptions, are assessed before the intervention ("T0"), at 8 weeks ("T1" corresponding to the end of SPACO + program's session period) and then 3 months later ("T2").

DISCUSSION: If the SPACO + program is effective and accepted by professionals and patients, it could be disseminated in other regions to assess its transferability. The medico-economic evaluation will also make it possible to assess the benefits provided.

TRIAL REGISTRATION: This trial is registered under the number NCT05787366 (March 24, 2023). Protocol Version N°3.0 (May 31, 2024).

RevDate: 2025-04-29

Rane Levendovszky S, Patel P, Zhu C, et al (2025)

Neuroimaging Biomarkers of Post-acute Sequelae of Covid (PASC).

The British journal of radiology pii:8121936 [Epub ahead of print].

COVID-19, caused by SARS-CoV-2, has led to the condition known as Long COVID or post-acute sequelae of COVID-19 (PASC), where individuals experience persistent debilitating symptoms long after the initial infection. We provide here a comprehensive review of findings in the central nervous system associated with PASC. Neuroimaging has been instrumental in identifying brain changes associated with PASC. Structural MRI studies consistently reveal gray matter volume reductions in the frontal and temporal lobes and white matter hyperintensities, particularly in the periventricular regions. Studies especially found these changes to correlate strongly with cognitive deficits. Diffusion tensor imaging has shown increased tissue damage and edema in the brain's white matter tracts, particularly in the sagittal stratum and thalamic radiation. Resting-state functional MRI studies indicate altered brain connectivity in PASC patients, especially in those with post-traumatic stress symptoms. Reduced connectivity within and between critical networks, such as the default mode network and the executive control network, has been observed. These changes correlate with cognitive impairments, such as attention and memory deficits. Dynamic functional connectivity analyses further reveal that PASC patients spend less time in states with rich inter-regional connectivity, and transitions between connectivity states were linked to post-traumatic stress disorder symptoms. Positron emission tomography scans have shown hypometabolism in the frontal and temporal lobes, particularly in regions associated with memory and executive functions. Hypometabolism in the hippocampus and thalamus is linked to symptoms like anosmia and fatigue. Despite the heterogeneity in clinical presentations and diagnostic criteria, these neuroimaging findings underscore the significant impact of COVID-19 on brain structure and function. Continued research using advanced imaging techniques is essential for a deeper understanding of PASC's neurological effects. This will aid in developing targeted interventions and improving outcomes for those affected by Long COVID and inform studies investigating downstream effects of viral infections on the brain.

RevDate: 2025-04-29
CmpDate: 2025-04-29

Carpallo-Porcar B, Jiménez-Sánchez C, Calvo S, et al (2025)

ARACOV-02. Specialized nutritional intervention and telerehabilitation in patients with long COVID: Protocol of a randomized controlled trial.

PloS one, 20(4):e0321811.

BACKGROUND: It is estimated that at least 10% of the population infected with SARS-CoV-2 develop Post COVID Condition, which is characterized by a diverse array of symptoms including dyspnea, fatigue, anxiety, depression, and deterioration in quality of life. The SARS-CoV-2 virus can trigger an excessive immune response, characterized by the release of pro-inflammatory cytokines including IL-6, IL-1, TNFα and reactive oxygen species. Specialized Pro Resolving Mediators (SPMs) (17-HAD, 14-HAD and 18_HEPE) that could be useful in Post COVID Condition modulating the inflammatory response. The objective is to determine the change in quality of life, inflammatory profile, functional capacity and emotional variables in a group taking a nutritional supplement (SPMs) plus a telerehabilitation programme.

METHODS: ARACOV-2 study is a double-blind, parallel-group, randomized control trial with two parallel interventions: Nutritional supplement and telerehabilitation vs placebo supplement and telerehabilitation. The primary endpoint will be quality of life (EQ-5L-5D). The intervention will last 12 weeks with a daily intake of omega-3 or placebo and a daily supervised rehabilitation programme using telerehabilitation.

DISCUSSION: This study suggests that SPMs supplementation combined with telerehabilitation may improve inflammation and symptoms like fatigue in Post COVID Condition patients. Both interventions have anti-inflammatory potential, and their combined use could enhance physical and mental health outcomes. This approach offers a promising strategy for managing Post COVID Condition symptoms.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06063031.

RevDate: 2025-04-29
CmpDate: 2025-04-29

Schaefer CM, Krause TM, Delclos GL, et al (2025)

Risk of post-acute symptoms among adults: A comparison study of severe COVID-19, pneumonia, and influenza.

PloS one, 20(4):e0322020.

BACKGROUND: A retrospective cohort study was undertaken to assess the relationship between initial disease severity of COVID-19 and the risk of post-acute symptoms. The COVID-19 cohort was compared against influenza and pneumonia cohorts to assess whether risk of post-acute symptoms differed.

METHODS: Administrative health claims data were obtained for commercially insured and Medicare Advantage covered adults (≥ 18 years) with symptomatic laboratory-confirmed COVID-19 diagnosed in 2020 (n=121,205), and similar cohorts of influenza (n=20,844) and pneumonia (n=29,052) patients diagnosed prior to the pandemic. Post-acute symptoms were assessed at four weeks, three and six months following initial diagnosis.

RESULTS: Among the patients with COVID-19, the likelihood of any post-acute symptom increased with initial disease severity, and was also influenced by the presence of comorbidities, especially rheumatoid arthritis, ischemic heart disease and asthma. The specific post-acute symptoms varied by age, with increased risks of anxiety and headache among the young, whereas the elderly experienced increased brain fog and fatigue. When compared against the influenza and pneumonia cohorts, all three groups experienced post-acute symptoms, with a strong relationship to disease severity, and only partial resolution over the six-month observation period. Those with influenza were less likely than those with COVID-19 to experience post-acute symptoms while those with pneumonia were more likely to have post-acute illness than those with COVID-19.

CONCLUSIONS: Using a large national dataset, we found that COVID-19 symptomology could not be described by previously seen influenza or pneumonia symptomology and differences exist in the prevalence of symptoms as well as time to resolution, better characterizing "long COVID" and identifying that these differences are unique to COVID-19.

RevDate: 2025-04-29

Shariati M, Gill KL, Peddle M, et al (2025)

Long COVID and Associated Factors Among Chinese Residents Aged 16 Years and Older in Canada: A Cross-Sectional Online Study.

Biomedicines, 13(4):.

As the COVID-19 pandemic evolved, long COVID emerged as a significant threat to public health, characterized by one or more persistent symptoms impacting organ systems beyond 12 weeks of infection. Informative research has been derived from assessments of long COVID among the Chinese populace. However, none of these studies considered the COVID-19 experience of Chinese residents in Canada. Objectives: We aimed to fill this literature gap by delineating the long COVID experience, prevalence, and associated factors among a sample of Chinese residing in Canada during the pandemic. Methods: The present study employed a cross-sectional online survey questionnaire distributed to a sample of Canadian Chinese using a convenience sampling procedure from 22 December 2022 to 15 February 2023. Respondents were probed for sociodemographic background and health-, COVID-, and vaccine-related characteristics. Logistic LASSO regression was used for model building, and multivariate logistic regression was used to identify factors associated with developing long COVID. Results: Among 491 eligible participants, 63 (12.83%) reported experiencing long COVID with a mean duration of 5.31 (95% CI: 4.06-6.57) months and major symptoms including difficulty concentrating (21.67%), pain/discomfort (15.00%), as well as anxiety/depression (8.33%). Our final model identified significant associations between long COVID and two or more COVID-19 infections (OR = 23.725, 95% CI: 5.098-110.398, p < 0.0001), very severe/severe symptoms (OR = 3.177, 95% CI: 1.160-8.702, p = 0.0246), over-the-counter medicine (OR = 2.473, 95% CI: 1.035-5.909, p = 0.0416), and traditional Chinese medicine (OR = 8.259, 95% CI: 3.016-22.620, p < 0.0001). Further, we identified a significant protective effect of very good/good health status (OR = 0.247, 95% CI: 0.112-0.544, p = 0.0005). Conclusions: Long COVID effected a notable proportion of Canadian Chinese for a prolonged period during the COVID-19 pandemic. Our findings underscore the importance of preexisting health status and reinfection prevention when managing long COVID. Moreover, our work indicates an association between using over-the-counter medicine or traditional Chinese medicine and long COVID experience among Canadian Chinese.

RevDate: 2025-04-29
CmpDate: 2025-04-29

Cavalcanti CRS, Smaili SS, Citibaldi MH, et al (2025)

Public perception of the persistence of COVID-19 symptoms and potential strategies to address Long COVID.

Ciencia & saude coletiva, 30(4):e14312024.

Long COVID is characterized by symptoms that persist for more than 12 weeks after a SARS-CoV-2 infection. This study investigated public perceptions of long COVID in Brazil. Interviews were conducted with 1,295 participants selected based on variable quotas, according to the population distribution in each region of the country, using data from the 2021 National Household Sample Survey (PNAD) and the 2010 IBGE Census. The findings revealed that 40.6% reported having had COVID-19 between 2020 and 2023, with 33.4% experiencing persistent symptoms for at least three months. The most common symptoms included fatigue (44.6%), headache (43.7%), hair loss (40.9%), memory loss (34.7%), and difficulty concentrating (28.7%). The study highlights that Brazilians are unaware of the correlation between these symptoms and the acute phase of the disease. By increasing public awareness of the issue, society becomes more capable of demanding better healthcare services for long COVID and insisting on effective policies. The importance of social education on this topic is fundamental to improving the healthcare system.

RevDate: 2025-04-29
CmpDate: 2025-04-29

Caputo EL, Feter N, Delpino FM, et al (2025)

What changed after two years of COVID-19: the PAMPA Cohort update profile and methodology.

Ciencia & saude coletiva, 30(4):e06102023.

The PAMPA Cohort aimed to evaluate the long-term impact of the COVID-19 pandemic on the physical and mental health outcomes of adults. We present data from the fourth wave of the PAMPA Cohort, the updated cohort profile and methodology. The PAMPA Cohort is a prospective study initially designed to have three data collection waves (June 2020, December 2020, and June 2021). With the pandemic progression, three new waves were programmed in addition to the previous waves: 2022. 2023, and 2024. Participants answered about physical activity, mental health, low back pain, healthcare access, and COVID-19, among others. Overall, 2,691 participants answered the wave four. Physical activity levels increased, and symptoms of anxiety and depression were reduced compared to the first assessment. However, a high proportion of chronic diseases was observed, and one-third of participants experienced some degree of food insecurity. Additionally, three-quarters were classified as having long COVID. The indirect effects of the pandemic on both physical and mental health persist in the lives of individuals.

RevDate: 2025-04-30

Boese AS, Warner BM, McQueen P, et al (2024)

SARS-CoV-2 infection results in a unique lung proteome long after virus resolution in the hamster.

Npj viruses, 2(1):40.

Long COVID or post-acute sequelae of COVID-19 (PASC) remains an ongoing public health issue that causes impairment for those afflicted and diminishes their ability to contribute to society. To address the host response underpinning respiratory PASC, we used the Golden Syrian hamster model infected with ancestral SARS-CoV-2 and examined its lung proteome in a longitudinal experiment. We infected young 6-week old male and female hamsters with 10[5] TCID50 of virus via the intranasal route and sampled the lung at 1, 3, 5, and 31 days post infection (dpi). We compared the infected lung proteome to that of uninfected sex-matched controls. We found almost no differences in protein levels at 1 dpi, with hundreds at 3 dpi, and thousands at 5 dpi. Many overlapping differential protein levels and pathways were seen in both sexes at 3 and 5 dpi including the Coagulation and Complement cascades. Notably, we found differences between the sexes at 31 dpi which included many targets with decreased levels of protein in the males. We also noted an increase in 7 proteins in both sexes at 31 dpi including proteins responsible for airway mucosal layer integrity such as Mucin 5B and Calcium-activated chloride channel regulator 1. Longitudinally, 38 proteins were changed in levels across more than one timepoint in the males but only three proteins were in the females, Secretoglobin family 1 A member 1, Poly [ADP-ribose] polymerase, and Apolipoprotein D. Overall, we show that there are changes to the lung proteome at 31 dpi, a time when no SARS-CoV-2 remains, and that there are sex differences in that proteome after infection with the ancestral strain. We conclude that biological sex should be examined as a variable when testing medical countermeasures for PASC in the Golden Syrian hamster due to host differences between the sexes.

RevDate: 2025-04-30
CmpDate: 2025-04-30

Ocampo FF, KB Holroyd (2025)

Updates on the neurological manifestations of SARS-CoV-2 infection.

Current opinion in infectious diseases, 38(3):234-241.

PURPOSE OF REVIEW: Since its emergence in 2020, the COVID-19 pandemic has created a global surge of survivors experiencing neurologic effects from SARS-CoV-2 infection. This review aims to provide an updated synthesis of the acute and chronic neurological manifestations of COVID-19, and to outline the current therapeutic strategies for these conditions.

RECENT FINDINGS: Epidemiological studies have shown that COVID-19 patients with neurological symptoms during acute infection tend to have poorer hospital and functional outcomes. While the risk of adverse neurologic symptoms including cognitive dysfunction, headache, autonomic dysfunction, and chronic fatigue are thought to be greatest following infection with the original SARS-CoV-2 strain and its alpha variant, they remain prevalent after infection with subsequent less virulent strains as well. Some recent work has also found a link between SARS-CoV-2 and structural brain changes. However, ongoing trials show promising results for pharmacologic and nonpharmacologic treatments targeting the postacute neurological sequelae of COVID-19.

SUMMARY: Lingering neurological manifestations after COVID-19 still pose considerable individual, healthcare system, and socioeconomic repercussions. Both preventive and multimodal treatment approaches are necessary to address these conditions. Further research is required to assess the lasting impacts of SARS-CoV-2 on the nervous system, particularly its potential contribution to the development of neurodegenerative diseases.

RevDate: 2025-04-28
CmpDate: 2025-04-29

Gotelli E, Campitiello R, Pizzorni C, et al (2025)

Multicentre retrospective detection of nailfold videocapillaroscopy abnormalities in long covid patients.

RMD open, 11(2): pii:rmdopen-2025-005469.

BACKGROUND: SARS-CoV-2 induces acute non-specific endothelial/microvascular alterations that have been identified by nailfold videocapillaroscopy (NVC). Details on NVC abnormalities in long covid (LC) patients (pts) are unknown.

METHODS: LC pts without and with systemic sclerosis (non-SSc-LC and SSc-LC), recovered COVID-19 (RC) pts that did not develop LC and healthy matched control subjects (CNT) that underwent NVC examinations were evaluated in a multicentre national study from the Capillaroscopy and Microcirculation in Rheumatic Diseases Study Group of the Italian Society of Rheumatology. Retrospective collection was performed for demographic data, course of SARS-CoV-2 infection, comorbidities, concomitant drugs. NVC alterations were quantified by validated scores. Pre-COVID-19 and post-COVID-19 microvascular status was analysed by NVC.

RESULTS: 62 non-SSc-LC pts (49 female/13 male, 51±16 years old), 24 SSc-LC pts (21 female/3 male, 59±17 years old), 23 RC pts (18 female/5 male, 51±18 years old) and 84 CNT (68 female/16 male, 52±12 years old) were analysed. Non-SSc-LC pts showed significantly more dilated capillaries (p<0.01, p multivariate<0.01), microhaemorrhages (p=0.01, p multivariate<0.05), abnormal shapes (p<0.05, p multivariate<0.05) than CNT and of note, lower mean capillary number per linear millimetre (p<0.01, p multivariate<0.01) than both RC pts and CTN (p<0.01, p multivariate<0.05).Of highest interest, 16 non-SSc-LC pts showed statistically significantly more dilated capillaries (p<0.05) and microhaemorrhages (p<0.05) in NVC examinations after COVID-19, compared with pre-COVID-19 status.Similarly, SSc-LC pts (24) showed significantly lower capillary density (p=0.01) and more dilated capillaries (p<0.01) in NVC examinations after COVID-19, compared with pre-COVID-19 status.

CONCLUSIONS: LC pts show more microvascular alterations at NVC as compared with RC patients and CNT, which may contribute to the pathogenesis of persistent organ/systems dysfunction.

RevDate: 2025-04-28

Sessford JD, Dodwell A, Elms K, et al (2025)

Factors associated with mental health outcomes among family caregivers to adults with COVID: a scoping review.

Disability and rehabilitation [Epub ahead of print].

PURPOSE: Family caregivers (FCGs) are essential to the health and wellbeing of people affected by COVID. Protecting mental health of FCGs is essential to sustaining their caregiving role. The objective of this scoping review was to synthesise identified risks factors and protective factors for mental health of FCGs to adults with COVID.

MATERIALS AND METHODS: Using the Joanna Briggs Institute (JBI) methodology, the search was conducted across Medline, CINAHL, and PsycINFO. Original studies conducted since the pandemic began were included. The population was adult FCGs to adults with COVID, and studies reported mental health outcomes and related factors.

RESULTS: Of 3474 identified articles, 22 met inclusion criteria (14 quantitative, seven qualitative, one mixed-methods, 18/22 conducted in Iran). Across all study designs, risk factors included limited support, financial burden, family challenges, unpredictable nature of COVID, inexperience, isolation, and unpleasant experiences. Protective factors included accessing support services, self-reinforcement, coping strategies, professional help, and online intervention.

CONCLUSIONS: Quantitative and qualitative research identified common mental health risk factors and protective factors for FCGs to adults with COVID. These factors may inform development of supports and services for FCGs to people with COVID, such as online interventions. Studies did not distinguish acute versus long COVID.

RevDate: 2025-04-28

Karaviti D, Charakida M, Dimopoulou D, et al (2025)

Long-term Effects of SARS-CoV-2 Infection on Children's Vasculature.

The Pediatric infectious disease journal pii:00006454-990000000-01302 [Epub ahead of print].

BACKGROUND: While long coronavirus disease 2019 (COVID-19) is linked to prolonged vascular dysfunction in adults, research in children remains poor. In this study, we assessed vascular health in children infected with severe acute respiratory syndrome coronavirus 2 about 6.8 months postinfection, comparing them with healthy controls.

METHODS: Two hundred twenty-three children were assessed and divided into group 1, which included children with a positive disease history and group 2, which consisted of healthy controls. Anthropometric measurements, lipid profile, biomarkers (interleukin-6, C-reactive protein, tumor necrosis factor-alpha and soluble intracellular adhesion molecule) and long COVID symptoms were assessed, along with pulse wave velocity (PWV) measurements and carotid intima-media thickness (cIMT) to evaluate aortic stiffness.

RESULTS: Children in group 1 were older (mean age: 10.8 ± 3.2 years vs. 8.5 ± 2.8 years, P < 0.001) and had higher body mass index (20.3 ± 5.6 kg/m2 vs. 18.4 ± 3.5 kg/m2, P < 0.001). PWV was increased in group 1 (5.02 ± 0.7 m/s vs. 4.7 ± 0.6, P < 0.001). However, vascular differences between the groups disappeared after adjusting for age, body mass index, and blood pressure. Soluble intracellular adhesion molecule-1 levels were elevated in children with a history of moderate/severe COVID-19 infection compared with controls (555.8 ± 113.2 ng/mL vs. 428 ± 42.6 ng/mL, P < 0.001). Cholesterol levels, inflammatory markers and cIMT were comparable between groups. Long COVID symptoms were reported mainly by participants of group 1 [34 (23.6%) vs. 3 (3.8%), P < 0.001].

CONCLUSIONS: This study demonstrates insights into the long-term effects of COVID-19 infection in children. Evidence of endothelial activation without structural arterial changes was found. Persistent inflammation postinfection was absent, yet approximately one-quarter of the participants experienced long COVID symptoms, indicating potential differences in the pathophysiology of postacute COVID-19 infection in childhood.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Although new treatments and vaccines have greatly reduced the acute threat of covid-19, many people who contract the disease find themselves with a persistent set of symptoms that are at best uncomfortable and at worst debilitating — long covid. R. Robbins

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