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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 22 Apr 2024 at 01:47 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: 2024-04-19

Wills CP, Perez B, J Moore (2024)

Coronavirus Disease 2019: Past, Present, and Future.

Emergency medicine clinics of North America, 42(2):415-442.

Severe acute respiratory syndrome coronavirus 2 is one of the most impactful diseases experienced in the past century. While the official national health emergency concluded in May of 2023, coronavirus disease 2019 (COVID-19) continues to mutate. As the summer of 2023, all countries were experiencing a new surge of cases from the EG.5 Omicron variant. Additionally, a new genetically distinct Omicron descendant BA2.86 had been detected in multiple countries including the United States. This article seeks to offer lessons learned from the pandemic, summarize best evidence for current management of patients with COVID-19, and give insights into future directions with this disease.

RevDate: 2024-04-19

Ye G, Zhu Y, Bao W, et al (2024)

The Long Coronavirus Disease (COVID) Symptom and Severity Score: Development, Validation, and Application.

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research pii:S1098-3015(24)02341-6 [Epub ahead of print].

OBJECTIVES: The primary focus of this research is the proposition of a methodological framework for the clinical application of the long coronavirus disease (COVID) Symptom and Severity Score (LC-SSS). This tool is not just a self-reported assessment instrument developed and validated but serves as a standardized, quantifiable means to monitor the diverse and persistent symptoms frequently observed in individuals suffering from long COVID.

METHODS: A three-stage process was used to develop, validate, and establish scoring standards for the LC-SSS. Validation measures included correlations with other patient-reported measures, confirmatory factor analysis, Cronbach's α for internal consistency, and test-retest reliability. Scoring standards were determined using K-means clustering, with comparative assessments made against Hierarchical clustering and the Gaussian Mixture Model (GMM).

RESULTS: The LC-SSS showed correlations with EQ-5D-5L (rs = -0.55), EQ-VAS (rs = -0.368), PHQ-9 (rs = 0.538), BAI (rs = 0.689), and ISI (rs = 0.516), confirming its construct validity. Structural validity was good with a CFI of 0.969, with Cronbach's α of 0.93 indicating excellent internal consistency. Test-retest reliability was also satisfactory (ICC = 0.732). K-means clustering identified three distinct severity categories in individuals living with long COVID, providing a basis for personalized treatment strategies.

CONCLUSIONS: The LC-SSS provides a robust and valid tool for assessing long COVID. The severity categories established via K-means clustering demonstrate significant variation in symptom severity, informing personalized treatment and improving care quality for long COVID patients.

RevDate: 2024-04-19

Chaze M, Mériade L, Rochette C, et al (2024)

Relying on the French territorial offer of thermal spa therapies to build a care pathway for long COVID-19 patients.

PloS one, 19(4):e0302392 pii:PONE-D-23-18949.

BACKGROUND: Work on long COVID-19 has mainly focused on clinical care in hospitals. Thermal spa therapies represent a therapeutic offer outside of health care institutions that are nationally or even internationally attractive. Unlike local care (hospital care, general medicine, para-medical care), their integration in the care pathways of long COVID-19 patients seems little studied. The aim of this article is to determine what place french thermal spa therapies can take in the care pathway of long COVID-19 patients.

METHODS: Based on the case of France, we carry out a geographic mapping analysis of the potential care pathways for long COVID-19 patients by cross-referencing, over the period 2020-2022, the available official data on COVID-19 contamination, hospitalisations in intensive care units and the national offer of spa treatments. This first analysis allows us, by using the method for evaluating the attractiveness of an area defined by David Huff, to evaluate the accessibility of each French department to thermal spas.

RESULTS: Using dynamic geographical mapping, this study describes two essential criteria for the integration of the thermal spa therapies offer in the care pathways of long COVID-19 patients (attractiveness of spa areas and accessibility to thermal spas) and three fundamental elements for the success of these pathways (continuity of the care pathways; clinical collaborations; adaptation of the financing modalities to each patient). Using a spatial attractiveness method, we make this type of geographical analysis more dynamic by showing the extent to which a thermal spa is accessible to long COVID-19 patients.

CONCLUSION: Based on the example of the French spa offer, this study makes it possible to place the care pathways of long COVID-19 patients in a wider area (at least national), rather than limiting them to clinical and local management in a hospital setting. The identification and operationalization of two geographical criteria for integrating a type of treatment such as a spa cure into a care pathway contributes to a finer conceptualization of the construction of healthcare pathways.

RevDate: 2024-04-19

Carstens M, Trujillo J, Dolmus Y, et al (2024)

Adipose-derived stromal vascular fraction cells to treat long-term pulmonary sequelae of coronavirus disease 2019: 12-month follow-up.

Cytotherapy pii:S1465-3249(24)00568-1 [Epub ahead of print].

BACKGROUND AIMS: Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components and can be obtained by small-volume lipoaspiration and administered on the same day. This study was designed to study the safety of AD SVF infused intravenously to treat the pulmonary symptoms of long COVID.

METHODS: Five subjects with persistent cough and dyspnea after hospitalization and subsequent discharge for COVID-19 pneumonia were treated with 40 million intravenous autologous AD SVF cells and followed for 12 months, to include with pulmonary function tests and computed tomography scans of the lung.

RESULTS: SVF infusion was safe, with no significant adverse events related to the infusion out to 12 months. Four subjects had improvements in pulmonary symptoms, pulmonary function tests, and computed tomography scans, with some improvement noted as soon as 1 month after SVF treatment.

CONCLUSIONS: It is not possible to distinguish between naturally occurring improvement or improvement caused by SVF treatment in this small, uncontrolled study. However, the results support further study of autologous AD SVF as a treatment for long COVID.

RevDate: 2024-04-19

Ahuja H, Badhwar S, Edgell H, et al (2024)

Machine learning algorithms for detection of visuomotor neural control differences in individuals with PASC and ME.

Frontiers in human neuroscience, 18:1359162.

The COVID-19 pandemic has affected millions worldwide, giving rise to long-term symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) infection, colloquially referred to as long COVID. With an increasing number of people experiencing these symptoms, early intervention is crucial. In this study, we introduce a novel method to detect the likelihood of PASC or Myalgic Encephalomyelitis (ME) using a wearable four-channel headband that collects Electroencephalogram (EEG) data. The raw EEG signals are processed using Continuous Wavelet Transform (CWT) to form a spectrogram-like matrix, which serves as input for various machine learning and deep learning models. We employ models such as CONVLSTM (Convolutional Long Short-Term Memory), CNN-LSTM, and Bi-LSTM (Bidirectional Long short-term memory). Additionally, we test the dataset on traditional machine learning models for comparative analysis. Our results show that the best-performing model, CNN-LSTM, achieved an accuracy of 83%. In addition to the original spectrogram data, we generated synthetic spectrograms using Wasserstein Generative Adversarial Networks (WGANs) to augment our dataset. These synthetic spectrograms contributed to the training phase, addressing challenges such as limited data volume and patient privacy. Impressively, the model trained on synthetic data achieved an average accuracy of 93%, significantly outperforming the original model. These results demonstrate the feasibility and effectiveness of our proposed method in detecting the effects of PASC and ME, paving the way for early identification and management of the condition. The proposed approach holds significant potential for various practical applications, particularly in the clinical domain. It can be utilized for evaluating the current condition of individuals with PASC or ME, and monitoring the recovery process of those with PASC, or the efficacy of any interventions in the PASC and ME populations. By implementing this technique, healthcare professionals can facilitate more effective management of chronic PASC or ME effects, ensuring timely intervention and improving the quality of life for those experiencing these conditions.

RevDate: 2024-04-19

Zhao J, Xia F, Jiao X, et al (2024)

Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.

Frontiers in neurology, 15:1367974.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca[2+].

RevDate: 2024-04-19

Antoncecchi V, Antoncecchi E, Orsini E, et al (2024)

High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study.

International journal of cardiology. Cardiovascular risk and prevention, 21:200267.

BACKGROUND: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE).

RESULTS: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus.

CONCLUSION: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.

RevDate: 2024-04-19

Van Laake T, D Hitch (2024)

Supporting rehabilitation practice for COVID-19 recovery: a descriptive qualitative analysis of allied health perspectives.

Australian health review : a publication of the Australian Hospital Association pii:AH23210 [Epub ahead of print].

ObjectiveThe study aimed to explore the perspective of healthcare workers on the resources they need to provide quality rehabilitation for people recovering from coronavirus disease 2019 (COVID-19) infection.MethodsA descriptive qualitative approach using reflexive thematic analysis was employed. Focus groups and interviews were performed with nine healthcare workers (one intensive care unit physiotherapist, one respiratory therapist and seven occupational therapists) with experience treating patients recovering from COVID-19 infection within hospital and in the community. Verbatim transcripts were coded and analysed for themes.ResultsHealthcare workers perceive an urgent need for resources about recovery from COVID-19 infection to support quality care. They particularly want detailed guidance about potential trajectories of recovery, and what should be expected over time for people with long COVID. Many observed that this group of patients had higher oxygen requirement and experienced slower recovery than others with serious respiratory conditions. Supports for quality care do exist but were not perceived as sufficient by participants. They want any new resources developed to be accessible, quick to access and targeted to specific healthcare worker roles and services settings. Participants identified several barriers to accessing practice supports, including the time poor nature of health care and financial costs to both patients and healthcare workers.ConclusionHealthcare workers perceive an urgent need for the development of resources to support quality rehabilitation for people recovering from COVID-19 infection, to support best outcomes for this group of patients. Any resources developed must consider identified barriers to their access and use to maximise their impact.

RevDate: 2024-04-18

Kooner HK, Sharma M, McIntosh MJ, et al (2024)

[129]Xe MRI Ventilation Textures and Longitudinal Quality-of-Life Improvements in Long-COVID.

Academic radiology pii:S1076-6332(24)00156-9 [Epub ahead of print].

RATIONALE AND OBJECTIVES: It remains difficult to predict longitudinal outcomes in long-COVID, even with chest CT and functional MRI. [129]Xe MRI reflects airway dysfunction, measured using ventilation defect percent (VDP) and in long-COVID patients, MRI VDP was abnormal, suggestive of airways disease. While MRI VDP and quality-of-life improved 15-month post-COVID infection, both remained abnormal. To better understand the relationship of airways disease and quality-of-life improvements in patients with long-COVID, we extracted [129]Xe ventilation MRI textures and generated machine-learning models in an effort to predict improved quality-of-life, 15-month post-infection.

MATERIALS AND METHODS: Long-COVID patients provided written-informed consent to 3-month and 15-month post-infection visits. Pyradiomics was used to extract [129]Xe ventilation MRI texture features, which were ranked using a Random-Forest classifier. Top-ranking features were used in classification models to dichotomize patients based on St. George's Respiratory Questionnaire (SGRQ) score improvement greater than the minimal-clinically-important-difference (MCID). Classification performance was evaluated using the area under the receiver-operator-characteristic-curve (AUC), sensitivity, and specificity.

RESULTS: 120 texture features were extracted from [129]Xe ventilation MRI in 44 long-COVID participants (54 ± 14 years), including 30 (52 ± 12 years) with ΔSGRQ≥MCID and 14 (58 ± 18 years) with ΔSGRQ
CONCLUSION: A machine learning model exclusively trained on [129]Xe MRI ventilation textures explained improved SGRQ-scores 12 months later, and outperformed clinical models. Their unique spatial-intensity information helps build our understanding about long-COVID airway dysfunction.

RevDate: 2024-04-18

Lee JD, TM Woodruff (2024)

Complement(ing) long-COVID thromboinflammation and pathogenesis.

Trends in immunology pii:S1471-4906(24)00069-3 [Epub ahead of print].

The persistence or recurrence of symptoms after acute SARS-CoV-2 infection, termed 'long COVID', presents a formidable challenge to global healthcare systems. Recent research by Cervia-Hasler and colleagues delves into the intricate immunological landscape in patients with long COVID, demonstrating an interplay between complement and coagulation, driven by antiviral antibodies and tissue damage.

RevDate: 2024-04-18

Bradley J, Xu Q, Touloumes N, et al (2024)

Association of Pulmonary Function Test Abnormalities and Quality-of-Life Measures after COVID-19 Infection.

The American journal of the medical sciences pii:S0002-9629(24)01170-4 [Epub ahead of print].

BACKGROUND: Long-COVID is a multisystem disease that can lead to significant impairments in health-related quality of life (HRQoL). Following COVID-19 infection, abnormalities on pulmonary function tests (PFT) are common. The primary aim of this study is to evaluate for any correlation between PFT abnormalities and impairment in HRQoL scores following COVID-19 infection.

METHODS: This is an analysis of a prospective cohort of patients in Louisville, KY who were infected with COVID-19. Data collected included demographics, past medical history, laboratory tests, PFTs, and several HRQoL questionnaires such as the EuroQol 5 Dimension HRQoL questionnaire (EQ-5D-5L), Generalized Anxiety Disorder 7 (GAD-7), Patient Health Questionnaire (PHQ-9), and Posttraumatic stress disorder checklist for DSM-5 (PCL-5). Descriptive statistics were performed, comparing PFTs (normal vs abnormal) and time since COVID-19 infection (3- vs 6- vs ≥ 12 months).

RESULTS: There were no significant differences in FEV1, FVC, or the percentage of patients with abnormal PFTs over time after COVID-19 infection. Following COVID-19, patients with normal PFTs had worse impairment in mobility HRQoL scores and change in GAD-7 scores over time. There were no differences over time in any of the HRQoL scores among patients with abnormal PFTs.

CONCLUSIONS: Among patients with an abnormal PFT, there was no temporal association with HRQoL scores as measured by EQ-5D-5L, GAD-7, PHQ-9, and PCL-5. Among patients with a normal PFT, mobility impairment and anxiety may be associated with COVID-19 infection. Following COVID-19 infection, impairment in HRQoL scores is not completely explained by the presence of abnormalities on spirometry.

RevDate: 2024-04-18

Clutterbuck D, Ramasawmy M, Pantelic M, et al (2024)

Barriers to healthcare access and experiences of stigma: Findings from a coproduced Long Covid case-finding study.

Health expectations : an international journal of public participation in health care and health policy, 27(2):e14037.

BACKGROUND AND AIM: Long Covid is often stigmatised, particularly in people who are disadvantaged within society. This may prevent them from seeking help and could lead to widening health inequalities. This coproduced study with a Community Advisory Board (CAB) of people with Long Covid aimed to understand healthcare and wider barriers and stigma experienced by people with probable Long Covid.

METHODS: An active case finding approach was employed to find adults with probable, but not yet clinically diagnosed, Long Covid in two localities in London (Camden and Merton) and Derbyshire, England. Interviews explored the barriers to care and the stigma faced by participants and were analysed thematically. This study forms part of the STIMULATE-ICP Collaboration.

FINDINGS: Twenty-three interviews were completed. Participants reported limited awareness of what Long Covid is and the available pathways to management. There was considerable self-doubt among participants, sometimes reinforced by interactions with healthcare professionals (HCPs). Participants questioned their deservedness in seeking healthcare support for their symptoms. Hesitancy to engage with healthcare services was motivated by fear of needing more investigation and concerns regarding judgement about the ability to carry out caregiving responsibilities. It was also motivated by the complexity of the clinical presentation and fear of all symptoms being attributed to poor mental health. Participants also reported trying to avoid overburdening the health system. These difficulties were compounded by experiences of stigma and discrimination. The emerging themes reaffirmed a framework of epistemic injustice in relation to Long Covid, where creating, interpreting and conveying knowledge has varied credibility based on the teller's identity characteristics and/or the level of their interpretive resources.

CONCLUSION: We have codeveloped recommendations based on the findings. These include early signposting to services, dedicating protected time to listening to people with Long Covid, providing a holistic approach in care pathways, and working to mitigate stigma. Regardless of the diagnosis, people experiencing new symptoms must be encouraged to seek timely medical help. Clear public health messaging is needed among communities already disadvantaged by epistemic injustice to raise awareness of Long Covid, and to share stories that encourage seeking care and to illustrate the adverse effects of stigma.

This study was coproduced with a CAB made up of 23 members including HCPs, people with lived experience of Long Covid and other stakeholders.

RevDate: 2024-04-18

Sarıcaoğlu EM, Çınar G, Azap A, et al (2023)

Dark Side of the COVID-19 Pandemic; 'Long COVID'.

Infectious diseases & clinical microbiology, 5(3):205-211.

OBJECTIVE: Besides its morbidity and mortality all over the world, SARS-CoV-2 infection maintains its importance with prolonged symptoms after acute disease. The post-infectious period including a heterogeneous group of symptoms is named 'long COVID'. This study aimed to describe persisting symptoms three months after COVID-19 and risk factors associated with 'long COVID'.

MATERIALS AND METHODS: This cross-sectional retrospective study included COVID-19 patients diagnosed with SARS-CoV-2 PCR positivity in the first 18 months of the COVID-19 pandemic, between March 2020 and September 2021. We conducted a survey in 2022 to inquire about the participants' symptoms that lasted three months or more after their own COVID-19 period. All patients were employees of one of the biggest national banks in Turkey. Participants answered a total of 31 questions over the phone. The presence of one or more symptoms persisting ≥3 months was defined as 'long COVID'. The risk factors associated with 'long COVID' were determined.

RESULTS: A total of 1301 patients were included in our study. The median age of patients was 40 (22-57), and 558 (42.9%) were women. 257 (19.8%) patients had 'long COVID' symptoms. The most prevalent symptoms were myalgia (14.3%), arthralgia (14.1%), and back pain (13.8%). Female gender (p=0.000, OR=2.19 [95% CI=1.655-2.904]) and diabetes mellitus (p=0.016, OR=2.43 [95% CI=1.177-5.017]) were found as independent risk factors for 'long COVID' by multivariant logistic regression analysis.

CONCLUSION: Female gender and diabetes mellitus are risk factors for 'long COVID'. Detecting patients with a high risk for developing 'long COVID' is crucial for their management during the COVID and post-COVID periods.

RevDate: 2024-04-18

Yalçın-Çolak N, Kader Ç, Eren-Gök Ş, et al (2023)

Long-Term Symptoms and Quality of Life in Persons with COVID-19.

Infectious diseases & clinical microbiology, 5(3):212-220.

OBJECTIVE: After three years since the first cases of COVID-19, many people suffer from post-COVID symptoms, reducing their quality of life. In this study, we aimed to evaluate the symptoms and prevalence of long COVID and its effect on the quality of life and also the effect of SARS-CoV-2 vaccine on the quality of life.

MATERIALS AND METHODS: Patients with COVID-19 between April 01, 2020, and December 31, 2021, were evaluated with a survey at least three and at most 12 months (mean 7.43±3.3 months) after diagnosis. Patients answered the questions face-to-face or via telephone interview. The survey included questionnaires on demographic features, current complaints, and complaints that persisted or developed after recovery, Short Form 36 Health Survey (SF-36), and European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) Scale.

RESULTS: The study was conducted with 521 participants, 81% complaining of post-COVID symptoms. The most common symptoms were fatigue and shortness of breath. Long COVID was found to significantly reduce the quality of life in both sub-dimensions of the scale. Compared to SF-36 Turkish population norms, all participants showed a significant decrease in quality of life subscales. Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was found to improve quality of life and reduce long-term COVID-19 symptoms.

CONCLUSION: COVID-19 has significantly affected quality of life. Post-illness follow-up of people with COVID-19 is important to provide patients with medical, physical, and psychosocial rehabilitation support. SARS-COV-2 vaccine reduces the negative effects of COVID-19 on quality of life. For this reason, the community should be made aware of vaccination, and COVID-19 vaccination rates should be increased in the community.

RevDate: 2024-04-17

Phetsouphanh C, Jacka B, Ballouz S, et al (2024)

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection.

Nature communications, 15(1):3315.

This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4[+] T cells, PD-1, and TIM-3 expression on CD4[+] and CD8[+] T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-β, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.

RevDate: 2024-04-17

Matthews B, Datey Chakrabarty A, A Chakrabarty (2024)

Long-term cognitive effects of COVID-19 studied with repeated neuropsychological testing.

BMJ case reports, 17(4): pii:17/4/e256711.

COVID-19 has a wide range of clinical manifestations. Apart from respiratory symptoms, neurological manifestations and cognitive impairment are commonly seen. Due to lack of a clear consensus on the definition of long COVID a pragmatic approach of assessing change from neurological baseline has become prevalent. We present the case of a high functioning woman in her late 40s who had a mild course of acute illness but developed cognitive difficulties. No organic causes for her cognitive difficulties were found. Neuropsychological testing showed impairment in right frontal lobe functioning. The patient showed a response to empirical treatment with Attention deficit hyperactivity disorder (ADHD) medications. Repeat neuropsychological testing 1 year later showed continued dysfunction in executive functioning. We present the details of her test findings and discuss the proposed pathophysiology behind neurocognitive effects of long COVID.

RevDate: 2024-04-17

Kane AS, Godfrey M, Noval Rivas M, et al (2024)

The Spectrum of Postacute Sequelae of COVID-19 in Children: From MIS-C to Long COVID.

Annual review of virology [Epub ahead of print].

The effects of SARS-CoV-2 infection on children continue to evolve following the onset of the COVID-19 pandemic. Although life-threatening multisystem inflammatory syndrome in children (MIS-C) has become rare, long-standing symptoms stemming from persistent immune activation beyond the resolution of acute SARS-CoV-2 infection contribute to major health sequelae and continue to pose an economic burden. Shared pathophysiologic mechanisms place MIS-C and long COVID within a vast spectrum of postinfectious conditions characterized by intestinal dysbiosis, increased gut permeability, and varying degrees of immune dysregulation. Insights obtained from MIS-C will help shape our understanding of the more indolent and prevalent postacute sequelae of COVID and ultimately guide efforts to improve diagnosis and management of postinfectious complications of SARS-CoV-2 infection in children.

RevDate: 2024-04-17

McAlpine L, Zubair AS, Joseph P, et al (2024)

Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.

Neurology(R) neuroimmunology & neuroinflammation, 11(3):e200244.

OBJECTIVES: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.

METHODS: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.

RESULTS: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02).

DISCUSSION: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence. It is a retrospective cohort study.

RevDate: 2024-04-17

Reier-Nilsen T, Grønneberg C, Røine S, et al (2024)

Assessment of lung function variability documents airflow limitation in many patients with long covid.

Heliyon, 10(8):e29261.

BACKGROUND: It is estimated that 65 million people worldwide suffer from long covid (LC). Many LC symptoms are also reported by patients with airflow limitation, used to confirm asthma. The primary aim was to detect airflow limitation in LC patients by a methacholine bronchial provocation test (BPT) and if negative, by evaluation of diurnal variability in forced expiratory flow in 1 second (FEV1) over a two-weeks' period. The second aim was to assess responsiveness to asthma treatment on diurnal FEV1 variability and LC symptoms.

METHODS: Patients with LC for at least six months were recruited in this open diagnostic study. Burden of LC symptoms were reported on a 10-point Likert scale (0 = not troubled, 10 = extremely troubled) at inclusion and after three weeks' asthma treatment. A positive methacholine BPT was defined by an accumulated provocation dose (PD20)<8 μmol causing 20% fall in FEV1. App-based spirometer was used for diurnal FEV1 variability, deemed positive by diurnalvariability in FEV1 ≥12%.

RESULTS: Airflow limitation was documented by positive methacholine BPT in 8/30 (27%), or by excessive diurnal variability in FEV1 in 21/22 (95%) of the BPT negative LC patients. One patient dropped out due to personal issues. Three weeks' asthma treatment normalised mean diurnal FEV1 variability from 18.0% to 7.3%, p < 0.001. Significant reductions were observed for fatigue and dyspnoea, from 8.3 to 6.1, p < 0.001, and 3.0 to 0, p < 0.001, respectively.

CONCLUSION: This study indicate that airflow limitation may be detected in many LC patients if evaluation of diurnal variability in FEV1 is included in the diagnostics.

RevDate: 2024-04-17

Anderson GM, Cook EH, Blakely RD, et al (2024)

Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration.

Journal of inflammation research, 17:2169-2172.

We believe there are serious problems with a recently published and highly publicized paper entitled "Serotonin reduction in post-acute sequelae of viral infection." The blood centrifugation procedure reportedly used by Wong et al would produce plasma that is substantially (over 95%) depleted of platelets. Given this, their published mean plasma serotonin values of 1.2 uM and 2.4 uM for the control/contrast groups appear to be at least 30 to 60 times too high and should be disregarded. The plasma serotonin values reported for the long COVID and viremia patients also should be disregarded, as should any comparisons to the control/contrast groups. We also note that the plasma serotonin means for the two control/contrast groups are not in good agreement. In the "Discussion" section, Wong et al state that their results tend to support the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of COVID-19, and they encourage further clinical trials of SSRIs. While they state that, "Our animal models demonstrate that serotonin levels can be restored and memory impairment reversed by precursor supplementation or SSRI treatment", it should be noted that no data are presented showing an increase or restoration in circulating serotonin with SSRI administration. In fact, one would expect a marked decline in platelet serotonin due to SSRIs' effective inhibition of the platelet serotonin transporter. Wong et al hypothesize that problems of long COVID arise from too little peripheral serotonin. However, given the frequent presence of a hyperaggregation state in long COVID, and the known augmenting effects of platelet serotonin on platelet aggregation, it is plausible to suggest that reductions in platelet serotonin might be associated with a lessening of the cardiovascular sequelae of COVID-19.

RevDate: 2024-04-17

Bachrach RL, Tighe CA, Beyer N, et al (2024)

Sleep and Alcohol Use Among Veterans Living With Long COVID.

Journal of primary care & community health, 15:21501319241246992.

OBJECTIVES: Study objectives were to: (1) better understand sleep experiences and unhealthy alcohol use among Veterans with long COVID and (2) explore providers' perceptions of barriers and facilitators to delivering evidence-based care for sleep problems and unhealthy alcohol use in patients with long COVID.

METHODS: VA electronic health records were used to conduct chart reviews (n = 57) of patients evaluated in a VA COVID-19 Recovery Clinic during 1 calendar year; semi-structured interviews were completed with Veterans (n = 5) and clinicians (n = 7) recruited from the clinic. Veteran participants also completed quantitative, self-report measures assessing sleep- and alcohol-related experiences and behaviors.

RESULTS: Data from chart reviews and interviews suggested that Veterans with long COVID often had pre-existing sleep problems that were exacerbated during long COVID. Patients and providers agreed that sleep interventions would be beneficial and acceptable in the COVID-19 Recovery clinic. Conversely, few Veterans with long COVID had a pre-existing alcohol use disorder (AUD) diagnosis; alcohol use occurred less frequently and was less often discussed between patients and providers. Providers had mixed viewpoints on delivering alcohol-related care in the clinic; some were highly amenable, others were unsure whether patients would be receptive.

CONCLUSIONS: This study is among the first to take a mixed-method approach to understanding experiences of sleep-wake behaviors and unhealthy alcohol use in Veterans with long COVID. Characterizing sleep and alcohol-related experiences, examining associations with functioning, and exploring perspectives on treatment approaches is critical to support efforts to refine, personalize, and optimize evidence-based sleep and alcohol care for Veterans living with long COVID.

RevDate: 2024-04-16

Greene C, Connolly R, Brennan D, et al (2024)

Author Correction: Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.

RevDate: 2024-04-16

Niewolik J, Mikuteit M, Klawitter S, et al (2024)

Cluster analysis of long COVID symptoms for deciphering a syndrome and its long-term consequence.

Immunologic research [Epub ahead of print].

The long-term symptoms of COVID-19 are the subject of public and scientific discussions. Understanding how those long COVID symptoms co-occur in clusters of syndromes may indicate the pathogenic mechanisms of long COVID. Our study objective was to cluster the different long COVID symptoms. We included persons who had a COVID-19 and assessed long-term symptoms (at least 4 weeks after first symptoms). Hierarchical clustering was applied to the symptoms as well as to the participants based on the Euclidean distance h of the log-values of the answers on symptom severity. The distribution of clusters within our cohort is shown in a heat map.From September 2021 to November 2023, 2371 persons with persisting long COVID symptoms participated in the study. Self-assessed long COVID symptoms were assigned to three symptom clusters. Cluster A unites rheumatological and neurological symptoms, cluster B includes neuro-psychological symptoms together with cardiorespiratory symptoms, and a third cluster C shows an association of general infection signs, dermatological and otology symptoms. A high proportion of the participants (n = 1424) showed symptoms of all three clusters. Clustering of long COVID symptoms reveals similarities to the symptomatology of already described syndromes such as the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or rheumatological autoinflammatory diseases. Further research may identify serological parameters or clinical risk factors associated with the shown clusters and might improve our understanding of long COVID as a systemic disease. Furthermore, multimodal treatments can be developed and scaled for symptom clusters and associated impairments.

RevDate: 2024-04-16

Mühlhauser I, Pantel J, G Meyer (2024)

[Evaluation of the public health measures introduced during the coronavirus pandemic: Evidence-based risk communication must be a central topic].

Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen pii:S1865-9217(24)00052-7 [Epub ahead of print].

Evidence-based and comprehensible health information is a key element of evidence-based medicine and public health. The goal is informed decision-making based on realistic estimations of health risks and accurate expectations about benefits and harms of interventions. In Germany, standards of evidence-based risk information were poorly followed during the COVID-19 pandemic. Frequently, public information was biased, fragmentary and misleading. Pandemic-related threat scenarios induced emotional distress and unnecessary anxiety. A systematic and comprehensive evaluation of the pandemic measures is crucial, but still pending in Germany. A critical analysis of risk communication by experts, politicians and the media during the pandemic should be a key element of the evaluation process. Evaluation of decision making and media reporting during the pandemic should improve preparedness for future crises.

RevDate: 2024-04-16

Glover NA, Ivanova O, Sathar F, et al (2024)

Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa.

EClinicalMedicine, 71:102588 pii:S2589-5370(24)00167-6.

BACKGROUND: Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV.

METHODS: We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021 at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT.

FINDINGS: We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300 m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6% <80% predicted), DLCO (53.4% <80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200 cells/mm[3], BMI <18.5 kg/m[2] and >35 kg/m[2], and initial COVID-19 severity.

INTERPRETATION: This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies.

FUNDING: The Bavarian State Ministry of Science and Arts.

RevDate: 2024-04-16

Jeffrey K, Woolford L, Maini R, et al (2024)

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records: a national, retrospective, observational cohort study.

EClinicalMedicine, 71:102590 pii:S2589-5370(24)00169-X.

BACKGROUND: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development.

METHODS: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98-99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status.

FINDINGS: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38-67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4-26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive.

INTERPRETATION: The prevalence of long COVID presenting in general practice was estimated to be 0.02-1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach.

FUNDING: Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.

RevDate: 2024-04-15

Hersh Z, Weisband YL, Bogan A, et al (2024)

Impact of Long-COVID in children: a large cohort study.

Child and adolescent psychiatry and mental health, 18(1):48.

BACKGROUND: The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3-6 months after the date of diagnosis.

METHODS: A retrospective study of all Clalit Health Services members in Israel aged 1-16 years who tested positive for SARS-CoV-2 between April 1, 2020 and March 31, 2021. Controls, who had no previous diagnosis of COVID-19, were one-to-one matched to 65,548 COVID-19-positive children and teens, and were assigned the infection dates of their matches as their index date. Matching included age, sex, socio-economic score, and societal sector. Individuals were excluded from the study if they had severe medical conditions before the diagnosis such as cancer, diabetes, chronic respiratory diseases, and/or abnormal physiological development. Generalized Estimating Equations were used to estimate the associations between COVID-19 and the use of medical services. The analysis focused on the 3-6 months after the infection date. Adjustments were made for demographics and for the use of medical services 6-12 and 3-6 months before the infection date. The latter was necessary because of observed disparities in medical service utilization between the groups before the COVID-19 diagnosis, despite the matching process.

RESULTS: Statistically significant differences were only found for referrals for mental health services [adjusted relative-risk (RR) 1·51, 95%CI 1·15 - 1·96; adjusted risk-difference (RD) 0·001, 95%CI 0·0006 - 0·002], and medication prescriptions of any kind (RR 1·03, 95%CI 1·01-1·06; RD 0·01 95%CI 0·004 - 0·02).

CONCLUSIONS: The significant increase in medication prescriptions and mental health service referrals support the hypothesis that COVID-19 is associated with long-lasting morbidities in children and adolescents aged 1-16 years. However, the risk difference in both instances was small, suggesting a minor impact on medical services.

RevDate: 2024-04-15

Chan JF, Yuan S, Chu H, et al (2024)

COVID-19 drug discovery and treatment options.

Nature reviews. Microbiology [Epub ahead of print].

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.

RevDate: 2024-04-15

W O, N N, M C, et al (2023)

Acute Onset of Mania and Psychosis in the Context of Long-COVID: A Case Study.

Acute phase COVID-19 has been associated with an increased risk for several mental health conditions, but less is known about the interaction of long COVID and mental illness. Prior reports have linked long COVID to PTSD, depression, anxiety, obsessive compulsive symptoms, and insomnia. This case report describes a novel presentation of mania arising in the context of long COVID symptoms with attention given to possible interacting etiological pathways. The case report also highlights the need for integrated, multidisciplinary treatment to support patients whose alarming, confusing, and multidetermined symptoms increase risk of psychological deterioration.

RevDate: 2024-04-15

Tomasiewicz K, Woron J, Kobayashi A, et al (2024)

Post-COVID-19 syndrome in everyday clinical practice: interdisciplinary expert position statement endorsed by the Polish Society of Civilization Diseases.

Polish archives of internal medicine pii:16728 [Epub ahead of print].

Post-COVID-19 syndrome, also known as long-COVID-19 syndrome, is a complex set of symptoms that persist for weeks or months after recovery from the acute phase of COVID-19. These symptoms can affect various body systems, including the respiratory, nervous, cardiovascular, and digestive systems. The most common complaints are fatigue, shortness of breath, joint pain, taste and smell disorders, as well as problems with memory and concentration. The pathogenesis of the post-COVID-19 syndrome is complicated and not fully understood, but it is likely related to an overactive immune system, disturbances in the intestinal microbiome, and cell and tissue damage caused by the virus. Incorporating a multidisciplinary approach to treating and rehabilitating patients and further research into this syndrome's underlying mechanisms and therapy is crucial for understanding and effectively treating this complex and multi-faced condition.

RevDate: 2024-04-15

Rizzi G, E Albanese (2024)

Reply to the letter to the editor "before attributing impaired cognition in the elderly to COVID-19, all influencing factors must be considered".

Brain, behavior, & immunity - health, 37:100740.

RevDate: 2024-04-15

de Bruijn S, van Hoek AJ, Mutubuki EN, et al (2024)

Lower prevalence of post-Covid-19 Condition following Omicron SARS-CoV-2 infection.

Heliyon, 10(7):e28941.

OBJECTIVES: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections.

METHODS: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity, using validated questionnaires for four symptoms. PCC prevalence was estimated as the difference in prevalence of at least one significantly elevated symptom, identified by permutation test, in cases compared to population controls.

RESULTS: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n = 1672) and population controls (n = 2762). PCC prevalence was 10·4% for Omicron cases and 17·7% for Delta cases (n = 6855). In Omicron cases, severe fatigue and dyspnea were more prevalent in reinfected than primary infected, while severity of symptoms did not significantly differ between cases with a booster or primary vaccination course.

CONCLUSIONS: Prevalence of PCC is 41% lower after Omicron than Delta at three months. Reinfection seems associated with more severe long-term symptoms compared to first infection.

RevDate: 2024-04-14

Kirchberger I, Meisinger C, Warm TD, et al (2024)

Longitudinal course and predictors of health-related quality of life, mental health, and fatigue, in non-hospitalized individuals with or without post COVID-19 syndrome.

Health and quality of life outcomes, 22(1):32.

BACKGROUND: Long-term information on health-related quality of life (HRQOL) and mental health of non-hospitalized individuals with "post COVID-19 syndrome" (PCS) is scarce. Thus, the objectives of the present study were to compare HRQOL and mental health of individuals with and without PCS in a German sample of non-hospitalized persons after SARS-CoV-2 infection, to characterize the long-term course up to 2 years and to identify predictors for post COVID-19 impairments.

METHODS: Individuals with past SARS-CoV-2 infection were examined at the University Hospital of Augsburg from November 2020 to May 2021 and completed a postal questionnaire between June and November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. HRQOL was assessed using the Veterans RAND 12-Item Health Survey, mental health was measured by the Patient Health Questionnaire and the Fatigue Asessment Scale was used to assess fatigue severity. Multivariable linear regression models with inverse probability weighting were used to determine the association between PCS and health outcomes.

RESULTS: From the 304 participants (58.2% women, median age 52 years), 210 (69.1%) were classified as having PCS in median 26 months after SARS-CoV-2 infection. Persons with PCS showed significantly more often depressive and anxiety disorders. PCS was independently and significantly associated with higher levels of depression, post-traumatic stress and fatigue, as well as poorer physical and mental HRQOL in median 9 months as well as 26 months after SARS-CoV-2 infection. A large number of acute symptoms and a prior diagnosis of depression were independently associated with poor mental health and HRQOL. While post-traumatic stress and mental HRQOL improved from 9 months to 26 months post infection onset, depressiveness, fatigue and physical HRQOL remained stable in both, persons with and without PCS.

CONCLUSIONS: PCS in non-hospitalized persons after SARS-CoV-2 infection is often associated with long-term impairments of mental health and HRQOL outcomes.

RevDate: 2024-04-14

Greenhalgh T, Darbyshire JL, Lee C, et al (2024)

What is quality in long covid care? Lessons from a national quality improvement collaborative and multi-site ethnography.

BMC medicine, 22(1):159.

BACKGROUND: Long covid (post covid-19 condition) is a complex condition with diverse manifestations, uncertain prognosis and wide variation in current approaches to management. There have been calls for formal quality standards to reduce a so-called "postcode lottery" of care. The original aim of this study-to examine the nature of quality in long covid care and reduce unwarranted variation in services-evolved to focus on examining the reasons why standardizing care was so challenging in this condition.

METHODS: In 2021-2023, we ran a quality improvement collaborative across 10 UK sites. The dataset reported here was mostly but not entirely qualitative. It included data on the origins and current context of each clinic, interviews with staff and patients, and ethnographic observations at 13 clinics (50 consultations) and 45 multidisciplinary team (MDT) meetings (244 patient cases). Data collection and analysis were informed by relevant lenses from clinical care (e.g. evidence-based guidelines), improvement science (e.g. quality improvement cycles) and philosophy of knowledge.

RESULTS: Participating clinics made progress towards standardizing assessment and management in some topics; some variation remained but this could usually be explained. Clinics had different histories and path dependencies, occupied a different place in their healthcare ecosystem and served a varied caseload including a high proportion of patients with comorbidities. A key mechanism for achieving high-quality long covid care was when local MDTs deliberated on unusual, complex or challenging cases for which evidence-based guidelines provided no easy answers. In such cases, collective learning occurred through idiographic (case-based) reasoning, in which practitioners build lessons from the particular to the general. This contrasts with the nomothetic reasoning implicit in evidence-based guidelines, in which reasoning is assumed to go from the general (e.g. findings of clinical trials) to the particular (management of individual patients).

CONCLUSION: Not all variation in long covid services is unwarranted. Largely because long covid's manifestations are so varied and comorbidities common, generic "evidence-based" standards require much individual adaptation. In this complex condition, quality improvement resources may be productively spent supporting MDTs to optimise their case-based learning through interdisciplinary discussion. Quality assessment of a long covid service should include review of a sample of individual cases to assess how guidelines have been interpreted and personalized to meet patients' unique needs.

STUDY REGISTRATION: NCT05057260, ISRCTN15022307.

RevDate: 2024-04-15

Membrilla JA, Caronna E, Trigo-López J, et al (2021)

Persistent headache after COVID-19: Pathophysioloy, clinic and treatment.

Neurology perspectives, 1:S31-S36.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The acute infection is characterised not only by respiratory symptoms, but also by multiple systemic manifestations, including neurological symptoms. Among these, headache is a frequent complaint. As the pandemic progresses and the population of patients recovering from COVID-19 grows, it is becoming apparent that the headache present in the acute stage of the infection may persist for an indeterminate period, becoming a major problem for the patient and potentially leading to disability. In this review we describe the pathophysiological and clinical aspects of persistent headache after COVID-19 based on the information currently available in the literature and the authors' clinical experience.

RevDate: 2024-04-14

Lladós G, Massanella M, Paredes R, et al (2024)

'Vagus Nerve Dysfunction in the Post-COVID-19 Condition' - Author's reply.

RevDate: 2024-04-13

Guarnieri JW, Haltom JA, Albrecht YES, et al (2024)

SARS-CoV-2 Mitochondrial Metabolic and Epigenomic Reprogramming in COVID-19.

Pharmacological research pii:S1043-6618(24)00114-2 [Epub ahead of print].

To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.

RevDate: 2024-04-13

Wilmshurst P, Bewley S, P Murray (2023)

Hyperbaric oxygen therapy for the treatment of long COVID.

Clinical medicine (London, England), 23(1):99-100.

RevDate: 2024-04-13

Trinh NT, Jödicke AM, Català M, et al (2024)

Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway.

RevDate: 2024-04-13

Pulliam L, Sun B, McCafferty E, et al (2024)

Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.

International journal of molecular sciences, 25(7): pii:ijms25073830.

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

RevDate: 2024-04-13

Chagas LDS, CA Serfaty (2024)

The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond.

International journal of molecular sciences, 25(7): pii:ijms25073819.

Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.

RevDate: 2024-04-13

Werner CR, Fusco S, Kienzle K, et al (2024)

Incidence of Secondary Sclerosing Cholangitis in Hospitalized Long COVID-19 Patients: A Retrospective Single Center Study.

Diagnostics (Basel, Switzerland), 14(7): pii:diagnostics14070745.

BACKGROUND: SARS-CoV-2 infection and associated COVID-19 disease can lead to critical illness with a risk of developing a multiple organ failure. Subsequently, this may lead to various pathological sequelae, such as secondary sclerosing cholangitis after surviving COVID-19 (SSC-COVID).

OBJECTIVE: The aim is to retrospectively analyze a cohort of hospitalized patients with first-wave (February 2020-June 2020) SARS-CoV-2 infection and persisting unclear cholangiopathy to determine the incidence of SSC-COVID and its risk factors.

RESULTS: A total of 249 patients were hospitalized at the university hospital in Tübingen, Germany, with SARS-CoV-2 infection during the first wave of the pandemic. Of these, 35.3% (88/249) required intensive care treatment; 16.5% (41/249) of them died due to the complications of COVID-19; 30.8% (64/208) of surviving patients could be followed up und were retrospectively analyzed at our center. The incidence of confirmed SSC-COVID was 7.8% (5/64). All SSC-COVID patients had an ICU stay >20 days, for invasive ventilation, positioning treatment, vasopressor treatment, but possible risk factors for SSC were not significant due to the small number of patients.

CONCLUSIONS: SSC-COVID is an emerging disease in post-COVID patients with a high incidence in our single-center cohort. SSC-COVID should be considered as a differential diagnosis, if unclear cholangiopathy or cholestasis persists after SARS-CoV-2 infection.

RevDate: 2024-04-13

Makhluf H, Madany H, K Kim (2024)

Long COVID: Long-Term Impact of SARS-CoV2.

Diagnostics (Basel, Switzerland), 14(7): pii:diagnostics14070711.

Four years post-pandemic, SARS-CoV-2 continues to affect many lives across the globe. An estimated 65 million people suffer from long COVID, a term used to encapsulate the post-acute sequelae of SARS-CoV-2 infections that affect multiple organ systems. Known symptoms include chronic fatigue syndrome, brain fog, cardiovascular issues, autoimmunity, dysautonomia, and clotting due to inflammation. Herein, we review long COVID symptoms, the proposed theories behind the pathology, diagnostics, treatments, and the clinical trials underway to explore treatments for viral persistence, autonomic and cognitive dysfunctions, sleep disturbances, fatigue, and exercise intolerance.

RevDate: 2024-04-13

Sivan M, Smith AB, Osborne T, et al (2024)

Long COVID Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation.

Journal of clinical medicine, 13(7): pii:jcm13071908.

Background: Long COVID (LC) is a multisystem clinical syndrome with functional disability and compromised overall health. Information on LC clinical severity types is emerging in cross-sectional studies. This study explored the pattern and consistency of long COVID (LC) clinical severity types over time in a prospective sample. Methods: Participants with LC completed the condition-specific outcome measure C19-YRSm (Yorkshire Rehabilitation Scale modified version) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using the k-means partition method. Results: The study included cross-sectional data for 759 patients with a mean age of 46.8 years (SD = 12.7), 69.4% females, and a duration of symptoms of 360 days (IQR 217 to 703 days). The cluster analysis at first assessment revealed three distinct clinical severity type clusters: mild (n = 96), moderate (n = 422), and severe (n = 241). Longitudinal data on 356 patients revealed that the pattern of three clinical severity types remained consistent over time between the two assessments, with 51% of patients switching clinical severity types between the assessments. Conclusions: This study is the first of its kind to demonstrate that the pattern of three clinical severity types is consistent over time, with patients also switching between severity types, indicating the fluctuating nature of LC.

RevDate: 2024-04-13

Moro-López-Menchero P, Martín-Sanz MB, Fernandez-de-Las-Peñas C, et al (2024)

Living and Coping with Olfactory and Taste Disorders: A Qualitative Study of People with Long-COVID-19.

Healthcare (Basel, Switzerland), 12(7): pii:healthcare12070754.

Taste and smell disorders are common symptoms of SARS-CoV-2 acute infection. In post-COVID-19 condition, symptoms can persist leading to disruption in patients' lives, to changes in their coping skills, and to the need to develop strategies for everyday life. This study aimed to describe the perspective of a group of patients with Long-COVID-19, a condition where loss of taste and/or smell was the most predominant symptom. A qualitative descriptive study was conducted. Participants who had suffered SARS-CoV-2 infection and had Long-COVID-19 loss of taste and/or smell were recruited. Purposive sampling was applied, and participants were recruited until data redundancy was reached. In-depth interviews were used for data collection and thematic analysis was applied. Twelve COVID-19 survivors (75% women) were recruited. The mean age of the participants was 55 years, and the mean duration of post-COVID-19 symptoms was 25 months. Three themes were identified: (a) Living with taste and smell disorders, describing the disorders they experience on a daily basis, how their life has changed and the accompanying emotions, (b) Changes and challenges resulting from the loss of taste and smell, changes in habits, self-care and risk in certain jobs or daily activities, (c) Coping with taste and smell disorders, describing the daily strategies used and the health care received. In conclusion, Long-COVID-19 taste and/or smell disorders limit daily life and involve changes in habits, meal preparation, and the ability to detect potentially dangerous situations.

RevDate: 2024-04-13

Manhas KP, Horlick S, Krysa J, et al (2024)

Implementation of a Provincial Long COVID Care Pathway in Alberta, Canada: Provider Perceptions.

Healthcare (Basel, Switzerland), 12(7): pii:healthcare12070730.

A novel, complex chronic condition emerged from the COVID-19 pandemic: long COVID. The persistent long COVID symptoms can be multisystem and varied. Effective long COVID management requires multidisciplinary, collaborative models of care, which continue to be developed and refined. Alberta's provincial health system developed a novel long COVID pathway. We aimed to clarify the perspectives of multidisciplinary healthcare providers on the early implementation of the provincial long COVID pathway, particularly pathway acceptability, adoption, feasibility, and fidelity using Sandelowki's qualitative description. Provider participants were recruited from eight early-user sites from across the care continuum. Sites represented primary care (n = 4), outpatient rehabilitation (n = 3), and COVID-19 specialty clinics (n = 2). Participants participated in structured or semi-structured virtual interviews (both group and 1:1 were available). Structured interviews sought to clarify context, processes, and pathway use; semi-structured interviews targeted provider perceptions of pathway implementation, including barriers and facilitators. Analysis was guided by Hsieh and Shannon as well as Sandelowski. Across the eight sites that participated, five structured interviews (n = 13 participants) and seven semi-structured interviews (n = 15 participants) were completed. Sites represented primary care (n = 4), outpatient rehabilitation (n = 3), and COVID-19 specialty clinics (n = 2). Qualitative content analysis was used on transcripts and field notes. Provider perceptions of the early implementation outcomes of the provincial long COVID pathway revealed three key themes: process perceptions; awareness of patient educational resources; and challenges of evolving knowledge.

RevDate: 2024-04-12

Diexer S, Klee B, Gottschick C, et al (2024)

Insights into early recovery from Long COVID-results from the German DigiHero Cohort.

Scientific reports, 14(1):8569.

65 million people worldwide are estimated to suffer from long-term symptoms after their SARS-CoV-2 infection (Long COVID). However, there is still little information about the early recovery among those who initially developed Long COVID, i.e. had symptoms 4-12 weeks after infection but no symptoms after 12 weeks. We aimed to identify associated factors with this early recovery. We used data from SARS-CoV-2-infected individuals from the DigiHero study. Participants provided information about their SARS-CoV-2 infections and symptoms at the time of infection, 4-12 weeks, and more than 12 weeks post-infection. We performed multivariable logistic regression to identify factors associated with early recovery from Long COVID and principal component analysis (PCA) to identify groups among symptoms. 5098 participants reported symptoms at 4-12 weeks after their SARS-CoV-2 infection, of which 2441 (48%) reported no symptoms after 12 weeks. Men, younger participants, individuals with mild course of acute infection, individuals infected with the Omicron variant, and individuals who did not seek medical care in the 4-12 week period after infection had a higher chance of early recovery. In the PCA, we identified four distinct symptom groups. Our results indicate differential risk of continuing symptoms among individuals who developed Long COVID. The identified risk factors are similar to those for the development of Long COVID, so people with these characteristics are at higher risk not only for developing Long COVID, but also for longer persistence of symptoms. Those who sought medical help were also more likely to have persistent symptoms.

RevDate: 2024-04-12

Slurink IAL, van den Houdt SCM, G Mertens (2024)

Who develops long COVID? Longitudinal pre-pandemic predictors of long COVID and symptom clusters in a representative Dutch population.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases pii:S1201-9712(24)00118-8 [Epub ahead of print].

OBJECTIVES: Prior studies show that long COVID has a heterogeneous presentation. Whether specific risk factors are related to subclusters of long COVID remains unknown. This study aimed to determine pre-pandemic predictors of long COVID and symptom clustering.

METHODS: 3022 participants of a panel representative of the Dutch population completed an online survey about long COVID symptoms. Data was merged to 2018/2019 panel data covering sociodemographic, medical, and psychosocial predictors. A total of 415 participants were classified as having long COVID. K-means clustering was used to identify patient clusters. Multivariate and lasso regression was used to identify relevant predictors compared to a COVID-19 positive control group.

RESULTS: Predictors of long COVID included Western ethnicity, BMI, chronic disease, COVID-19 reinfections, severity, and symptoms, lower self-esteem, and higher positive affect (AUC=0.80, 95%CI 0.73-0.86). Four clusters were identified: a low and a high symptom severity cluster, a smell-taste and respiratory symptoms cluster, and a neuro-cognitive, psychosocial, and inflammatory symptom cluster. Predictors for the different clusters included regular health complaints, healthcare use, fear of COVID-19, anxiety, depressive symptoms, and neuroticism.

CONCLUSIONS: A combination of sociodemographic, medical, and psychosocial factors predicted long COVID. Heterogenous symptom clusters suggest that there are different phenotypes of long COVID presentation.

RevDate: 2024-04-12

Rafieian M, Skokauskas N, Cheslack-Postava K, et al (2024)

The association between intolerance of uncertainty and depressive symptoms during COVID-19 in New York, USA.

Journal of affective disorders pii:S0165-0327(24)00636-0 [Epub ahead of print].

BACKGROUND: Coronavirus Disease 2019 (COVID-19), a highly contagious respiratory illnesses, has globally impacted mental health. This study aims to investigate the association between intolerance of uncertainty and depressive symptoms during the pandemic in New York, USA, considering COVID-19-related worries as modifiers and mediators.

METHOD: 1227 participants from three ongoing cohort studies, originally centered on trauma-exposed children and adolescents, provided data via questionnaires and telephone interviews across three waves. We used multivariable logistic and linear regression models to investigate the intolerance of uncertainty-depressive symptoms relationship, while adjusting for potential confounders and assessing the modification and mediation effects of Covid-19 related worries.

RESULTS: Depressive symptoms prevalence was 18 %, 12 %, and 9 % at waves 0, 1, and 2 respectively. Strong positive associations were observed between intolerance of uncertainty above the median and depressive symptoms which remained significant after adjusting for potential confounders. Odds ratios were 2.14 (95 % CI: 1.54-2.99) and 4.50 (95 % CI: 2.67-7.93) for intolerance of uncertainty-depressive symptoms association at wave 0 and 1 respectively, and 3.22 (95 % CI: 1.68-6.63) for intolerance of uncertainty at wave 1 and depressive symptoms at wave 2. There was evidence of partial mediation by worries (12-37 %), but no evidence of a moderating effect.

LIMITATION: It includes study's methodology, including self-report measures, remote data collection, and uncontrolled variables like anxiety and COVID-19 perspectives.

CONCLUSION: The findings emphasize the importance of evidence-based strategies for tackling intolerance of uncertainty during pandemics, particularly in managing long COVID. Collaborative efforts between policymakers and clinicians are essential in this endeavor.

RevDate: 2024-04-12

Hadidchi R, Wang SH, Rezko D, et al (2024)

SARS-CoV-2 infection increases long-term multiple sclerosis disease activity and all-cause mortality in an underserved inner-city population.

Multiple sclerosis and related disorders, 86:105613 pii:S2211-0348(24)00192-5 [Epub ahead of print].

BACKGROUND: Although certain subsets patients with multiple sclerosis (MS), an immune-mediated disorder, are at higher risk of worse acute COVID-19 outcomes compared to the general population, it is not clear whether SARS-CoV-2 infection impacts long-term outcomes compared with MS patients without COVID-19 infection.

OBJECTIVES: This study investigated MS disease activity and mortality 3.5 years post SARS-CoV-2 infection and compared with MS patients without COVID-19.

METHODS: This retrospective study evaluated 1,633 patients with MS in the Montefiore Health System in the Bronx from January 2016 to July 2023. This health system serves a large minority population and was an epicenter for the early pandemic and subsequent surges of infection. Positive SARS-CoV-2 infection was determined by a positive polymerase-chain-reaction test. Primary outcomes were all-cause mortality, and optic neuritis post SARS-CoV-2 infection. Secondary outcomes included change in disease-modifying therapy (DMT), treatment with high-dose methylprednisolone, cerebellar deficits, relapse, and all-cause hospitalization post-infection.

RESULTS: MS patients with COVID-19 had similar demographics but higher prevalence of pre-existing major comorbidities (hypertension, type-2 diabetes, chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and coronary artery disease), optic neuritis, and history of high dose steroid treatment for relapses compared to MS patients without COVID-19. MS patients with COVID-19 had greater risk of mortality (adjusted HR=4.34[1.67, 11.30], p < 0.005), greater risk of post infection optic neuritis (adjusted HR=2.97[1.58, 5.58], p < 0.005), higher incidence of methylprednisolone treatment for post infection acute relapse (12.65% vs. 2.54 %, p < 0.001), and more hospitalization (78.92% vs. 66.81 %, p < 0.01), compared to MS patients without COVID-19.

CONCLUSIONS: MS patients who survived COVID-19 infection experienced worse long-term outcomes, as measured by treatment for relapse, hospitalization and mortality. Identifying risk factors for worse long-term outcomes may draw clinical attention to the need for careful follow-up of at-risk individuals post-SARS-CoV-2 infection.

RevDate: 2024-04-12

Dorronzoro-Zubiete E, Castro-Marrero J, Ropero J, et al (2024)

Personalized Management of Fatigue in Individuals With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Using a Smart Digital mHealth Solution: Protocol for a Participatory Design Approach.

JMIR research protocols, 13:e50157 pii:v13i1e50157.

BACKGROUND: Fatigue is the most common symptom in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, impacting patients' quality of life; however, there is currently a lack of evidence-based context-aware tools for fatigue self-management in these populations.

OBJECTIVE: This study aimed to (1) address fatigue in ME/CFS and long COVID through the development of digital mobile health solutions for self-management, (2) predict perceived fatigue severity using real-time data, and (3) assess the feasibility and potential benefits of personalized digital mobile health solutions.

METHODS: The MyFatigue project adopts a patient-centered approach within the participatory health informatics domain. Patient representatives will be actively involved in decision-making processes. This study combines inductive and deductive research approaches, using qualitative studies to generate new knowledge and quantitative methods to test hypotheses regarding the relationship between factors like physical activity, sleep behaviors, and perceived fatigue in ME/CFS and long COVID. Co-design methods will be used to develop a personalized digital solution for fatigue self-management based on the generated knowledge. Finally, a pilot study will evaluate the feasibility, acceptance, and potential benefits of the digital health solution.

RESULTS: The MyFatigue project opened to enrollment in November 2023. Initial results are expected to be published by the end of 2024.

CONCLUSIONS: This study protocol holds the potential to expand understanding, create personalized self-management approaches, engage stakeholders, and ultimately improve the well-being of individuals with ME/CFS and long COVID.

PRR1-10.2196/50157.

RevDate: 2024-04-12

Harris E (2024)

Trials Will Evaluate Treatments for Long COVID Nervous System Problems.

JAMA pii:2817558 [Epub ahead of print].

RevDate: 2024-04-12

Elfessi ZZ, Gardner J, Gordon HS, et al (2024)

Long COVID in Women Veterans Residing in Underserved, Socioeconomically Disadvantaged Neighborhoods of Chicago.

Population health management [Epub ahead of print].

RevDate: 2024-04-12

Gaudreau-Majeau F, Gagnon C, Djedaa SC, et al (2024)

Cardiopulmonary rehabilitation's influence on cognitive functions, psychological state, and sleep quality in long COVID-19 patients: A randomized controlled trial.

Neuropsychological rehabilitation [Epub ahead of print].

NCT05035628.Trial registration: ClinicalTrials.gov identifier: NCT05035628..

RevDate: 2024-04-12

Le GH, Kwan ATH, Guo Z, et al (2024)

Impact of Elevated Body Mass Index (BMI) on Cognitive Functioning and Inflammation in Persons with Post-COVID-19 Condition: A Secondary Analysis.

Acta neuropsychiatrica pii:S0924270824000164 [Epub ahead of print].

BACKGROUND: Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterized by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC.

METHODS: This is a post-hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impacts of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

RESULTS: Complete data from 70 participants were statistically analyzed and adjusted for age and sex. BMI is negatively correlated with performance on the DSST (β=-0.003, p=0.047), TMT-A (β=-0.006, p=0.025), and TMT-B (β=-0.006, p=0.002). BMI is positively correlated with serum CRP (unstandardized β=0.193, standardized β=0.612, p<0.001) and ESR (β=0.039, p<0.001) levels.

CONCLUSION: We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.

RevDate: 2024-04-11

Angulo-Aguado M, Carrillo-Martinez JC, Contreras-Bravo NC, et al (2024)

Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population.

Scientific reports, 14(1):8497.

Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral and host factors. These findings have highlighted the potential of host genetic markers to identify high-risk individuals and develop target interventions to reduce morbimortality. Despite its importance, genetic host factors remain largely understudied in Latin-American populations. Using a case-control design and a custom next-generation sequencing (NGS) panel encompassing 81 genetic variants and 74 genes previously associated with COVID-19 severity and long-COVID, we analyzed 56 individuals with asymptomatic or mild COVID-19 and 56 severe and critical cases. In agreement with previous studies, our results support the association between several clinical variables, including male sex, obesity and common symptoms like cough and dyspnea, and severe COVID-19. Remarkably, thirteen genetic variants showed an association with COVID-19 severity. Among these variants, rs11385942 (p < 0.01; OR = 10.88; 95% CI = 1.36-86.51) located in the LZTFL1 gene, and rs35775079 (p = 0.02; OR = 8.53; 95% CI = 1.05-69.45) located in CCR3 showed the strongest associations. Various respiratory and systemic symptoms, along with the rs8178521 variant (p < 0.01; OR = 2.51; 95% CI = 1.27-4.94) in the IL10RB gene, were significantly associated with the presence of long-COVID. The results of the predictive model comparison showed that the mixed model, which incorporates genetic and non-genetic variables, outperforms clinical and genetic models. To our knowledge, this is the first study in Colombia and Latin-America proposing a predictive model for COVID-19 severity and long-COVID based on genomic analysis. Our study highlights the usefulness of genomic approaches to studying host genetic risk factors in specific populations. The methodology used allowed us to validate several genetic variants previously associated with COVID-19 severity and long-COVID. Finally, the integrated model illustrates the importance of considering genetic factors in precision medicine of infectious diseases.

RevDate: 2024-04-11

Jiao T, Huang Y, Sun H, et al (2024)

Research progress of post-acute sequelae after SARS-CoV-2 infection.

Cell death & disease, 15(4):257.

SARS-CoV-2 has spread rapidly worldwide and infected hundreds of millions of people worldwide. With the increasing number of COVID-19 patients discharged from hospitals, the emergence of its associated complications, sequelae, has become a new global health crisis secondary to acute infection. For the time being, such complications and sequelae are collectively called "Post-acute sequelae after SARS-CoV-2 infection (PASC)", also referred to as "long COVID" syndrome. Similar to the acute infection period of COVID-19, there is also heterogeneity in PASC. This article reviews the various long-term complications and sequelae observed in multiple organ systems caused by COVID-19, pathophysiological mechanisms, diagnosis, and treatment of PASC, aiming to raise awareness of PASC and optimize management strategies.

RevDate: 2024-04-11

Couzin-Frankel J (2024)

Lessons in persistence.

Science (New York, N.Y.), 384(6692):150-154.

New Long Covid trials aim to clear lingering virus-and help patients in dire need.

RevDate: 2024-04-11

Massoumi LE, A Rosenbaum (2024)

Case Report on High Dose Lithium Treatment for Post-COVID Depression, Recurrent Fevers, and Skin Lesions.

Psychopharmacology bulletin, 54(2):39-45.

This is a case of a 35-year-old woman who presented with an 18-month history of post (long)-COVID depression and exhaustion along with recurrent fevers and treatment-resistant skin boils, all of which abated with lithium treatment at a serum level of 1.14 mmol/L, and all of which worsened when the lithium serum level was lowered to 0.8. This paper illustrates Lithium's effectiveness in the treatment of post (long)-COVID syndrome, though a higher serum concentration may be required.

RevDate: 2024-04-11

Silva MGS, Carvalho TL, de Azevedo Vieira JE, et al (2024)

Evaluating performance on the Glittre-ADL test in men with long COVID 3 years after a SARS-CoV-2 infection.

Journal of exercise science and fitness, 22(4):271-277.

BACKGROUND/OBJECTIVE: Many COVID-19 survivors, especially those who have been hospitalized, have been suffering numerous complications that limit their activities of daily living, although changes that persist 3 years after infection are still not known. We aimed to investigate the impact of long COVID on the Glittre-ADL test (TGlittre) 3 years after acute infection in men who needed hospitalization and explore whether the performance on the TGlittre is associated with impairments in lung function, muscle strength, physical function and quality of life (QoL).

METHODS: Cross-sectional study with 42 men with long COVID who took the TGlittre. They underwent pulmonary function tests and measurements of handgrip strength and quadriceps strength (QS). Additionally, they also completed the Saint George Respiratory Questionnaire (SGRQ) and Functional Independence Measure (FIM).

RESULTS: The mean age was 52 ± 10.6 years, while the mean time after diagnosis of COVID-19 was 37 ± 3.5 months. The mean TGlittre time was 3.3 (3.1-4.1) min, which was 10% greater than the time expected for normal individuals to complete it. The TGlittre time was correlated significantly with the QS (rs = -0.397, p = 0.009), pulmonary diffusion (rs = - 0.364, p = 0.017), FIM (rs = -0.364, p = 0.017) and the "activity" domain score of the SGRQ (rs = 0.327, p = 0.034).

CONCLUSION: Functional capacity on exertion as measured by the TGlittre time is normal in most men with long COVID 3 years after hospitalization. However, this improvement in functional capacity does not seem to be reflected in muscle strength or QoL, requiring continued monitoring even after 3 years.

RevDate: 2024-04-10

Domingo JC, Battistini F, Cordobilla B, et al (2024)

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

Journal of translational medicine, 22(1):343.

BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions.

METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses.

RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2[-] + NO3[-]) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1β (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population.

CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.

RevDate: 2024-04-10

Escaned J, Espejo-Paeres C, Jerónimo A, et al (2024)

Myocardial Ischemia of Nonobstructive Origin as a Cause of New-Onset Chest Pain in Long-COVID Syndrome.

JACC. Cardiovascular interventions, 17(7):958-960.

RevDate: 2024-04-10

Radkhah H, Omidali M, Hejrati A, et al (2023)

Correlations of Long COVID Symptoms and Inflammatory Markers of Complete Blood Count (CBC): A Cross-sectional Study.

Journal of community hospital internal medicine perspectives, 13(6):112-119.

BACKGROUND: Long-COVID refers to lasting unspecific symptoms like fatigue, decreased concentration and sleep issues after infection which persist for at least three months and cannot be attributed to other causes. Previous studies surveyed the association between inflammatory markers like C - reactive protein (CRP) at hospital admission and long-COVID symptoms in the preceding months. Post-COVID syndrome can affect one-third of patients. Thus early diagnosis can assist in reducing burdens on public health. We attempted to see any correlations between complete blood count (CBC) markers (like red blood cell (RBC), white blood cell (WBC), Neutrophil to lymphocyte ratio (NLR), etc.) at hospital admission and long COVID symptoms at a 6-month follow-up.

METHODS: 167 patients (44.9% females, mean age 49 years old) answered semi-structural interviews through telemedicine which focused on the three prominent symptoms: fatigue, loss of concentration and decreased libido. Results: Two third of patients have symptoms of long COVID and others do not have. NLR in the symptomatic group was statically higher. Patients who underwent decreased libido at a 6-month follow-up had significantly more severe lymphopenia (p = 0.028) and higher NLR values (p-value = 0.007). Poor mental concentration is associated with high WBC in numbers and polymorphonuclear (PMN) count. Other symptoms do not correlate with blood markers.

CONCLUSION: Utilizing available data like CBC can help predict the upcoming symptoms of previously hospitalized patients and further measures like rehabilitation. Additional investigations should be done on the effect of COVID vaccination on converting long COVID. Different variants of the virus may have different results.

RevDate: 2024-04-10

Barilaite E, Watson H, MB Hocaoglu (2024)

Understanding Patient-Reported Outcome Measures Used in Adult Survivors Experiencing Long-Term Effects After COVID-19 Infection: A Rapid Review.

Journal of patient-centered research and reviews, 11(1):36-50.

PURPOSE: Patient-reported outcome measures (PROMs) are used in individuals experiencing long-term effects from COVID-19 infection, or Long COVID, to evaluate the quality of life and functional status of these individuals. However, little is known about which PROMs are being utilised and the psychometric properties of these PROMs. Our purpose was thus to explore which PROMs are used in Long COVID patients and to discuss the psychometric properties of the PROMs.

METHODS: For this rapid review, a systematic literature search was performed in the PubMed, Embase, and CINAHL databases. The found studies were screened using the PRISMA flowchart. We then performed study quality appraisal and assessed the psychometric properties of the found PROMs.

RESULTS: Per the systematic literature search and after removal of duplicates, 157 publications were identified for individual screening. After screening and eligibility assessment, 74 articles were selected for our review. In total, 74 PROMs were used and primarily comprised quality of life, fatigue, breathlessness, mental health, and smell/taste issues in COVID "long haulers." Five studies used newly developed, COVID-19-specific PROMs. We assessed the psychometric properties of the 10 most-used PROMs. The majority were found to be reliable and valid instruments. EQ-5D-5L was the most popular and highly rated PROM.

CONCLUSIONS: We assessed PROMs used in Long COVID patients and evaluated their psychometric properties. EQ-5D-5L was the most favourably rated PROM. PROMs addressing mental health issues are crucial in managing anxiety and depression in Long COVID patients. New COVID-specific PROMs assess functional status and smell/taste perception and show great utilisation potential in olfactory training at COVID smell clinics. However, many reviewed PROMs currently lack sufficient analysis of their psychometric properties. Therefore, future research needs to examine these measures.

RevDate: 2024-04-10

Arêas GPT, Goulart CDL, Sant'Anna T, et al (2024)

Pulmonary Rehabilitation Associated with Noninvasive Ventilation on Physical Capacity and Quality of Life in Post-COVID-19: A Randomized Controlled Double-Blinded Clinical Trial Protocol.

Journal of multidisciplinary healthcare, 17:1483-1490.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pulmonary rehabilitation (PR) seems to be a better choice to improve physical and functional capacity after acute infection. However, there is a lack of evidence regarding the effects of different strategies to optimize post-acute phase rehabilitation and reduce long COVID-19 physical deteriorations.

OBJECTIVE: To compare the use of a noninvasive ventilation (NIV) plus aerobic exercise strategy during PR program with to a standard PR (without NIV) on physical capacity and quality of life outcomes in post-COVID-19.

METHODS: Double-blinded randomized controlled clinical trial. A total of 100 individuals discharged from hospital in a post-acute phase of severe COVID-19 will be randomized into two groups: PR + NIV (Group 1) and PR (Group 2). Inclusion criteria include participants who present symptomatic dyspnea II and III by the modified Medical Research Council, aged 18 years or older. Both groups will receive aerobic and resistance exercise, and inspiratory muscle training. However, group 1 will perform aerobic training with bilevel NIV. Cardiopulmonary exercise test will assess the O2 peak uptake, 6-minute walk test will assess the walking distance and short-form 36 will assess the quality of life before and after 8 weeks (after 24 PR sessions). Moreover, patients will be contacted by telephone every 3 months for one year to record possible adverse events, hospitalizations, and death. All data will be registered in RedCap, and analyses will be performed in the STATA v13 software.

CLINICAL TRIAL REGISTRATION: RBR-3t9pkzt.

RevDate: 2024-04-09

Cooper L, Xu H, Polmear J, et al (2024)

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Immunity pii:S1074-7613(24)00137-7 [Epub ahead of print].

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet[+] subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c[+]CD80[+] cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

RevDate: 2024-04-10

Kuut TA, Müller F, Csorba I, et al (2024)

Positive Effects of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following COVID-19 Are Sustained Up to 1 Year After Treatment.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 78(4):1078-1079.

RevDate: 2024-04-09

Durstenfeld MS, Weiman S, Holtzman M, et al (2024)

Long COVID and post-acute sequelae of SARS-CoV-2 pathogenesis and treatment: A Keystone Symposia report.

Annals of the New York Academy of Sciences [Epub ahead of print].

In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post-acute sequelae of COVID-19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism-focused randomized, placebo-controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post-infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post-infectious syndromes.

RevDate: 2024-04-09

Khodanovich M, Naumova A, Kamaeva D, et al (2024)

Neurocognitive Changes in Patients with Post-COVID Depression.

Journal of clinical medicine, 13(5): pii:jcm13051442.

Background: Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD, n = 25) patients using neuropsychological testing. Methods: The study involved 71 post-COVID patients with matched control groups: recovered COVID-19 individuals without complications (n = 18) and individuals without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, and a comparison group (noPCD, n = 46) included participants with neurological COVID-19 complications, excluding clinical depression. Results: The PCD patients showed gender-dependent significant cognitive impairment in the MoCA, Word Memory Test (WMT), Stroop task (SCWT), and Trail Making Test (TMT) compared to the controls and noPCD patients. Men with PCD showed worse performances on the SCWT, in MoCA attention score, and on the WMT (immediate and delayed word recall), while women with PCD showed a decline in MoCA total score, an increased processing time with less errors on the TMT, and worse immediate recall. No differences between groups in Sniffin's stick test were found. Conclusions: COVID-related direct (post-COVID symptoms) and depression-mediated (depression itself, male sex, and severity of COVID-19) predictors of decline in memory and information processing speed were identified. Our findings may help to personalize the treatment of depression, taking a patient's gender and severity of previous COVID-19 disease into account.

RevDate: 2024-04-09

Sárközi AT, Tornyi I, Békési E, et al (2024)

Co-Morbidity Clusters in Post-COVID-19 Syndrome.

Journal of clinical medicine, 13(5): pii:jcm13051457.

Background: Post-COVID-19 syndrome, characterized by persistent symptoms emerging more than 12 weeks after acute infection, displays diverse manifestations. This study aimed to analyze co-existing organ dysfunctions in post-COVID-19 patients and explore their potential association with the acute COVID-19 episode and functional impairment. Methods: Data from 238 patients attending post-COVID-19 outpatient care between 1 March 2021 and 1 March 2022, after previous hospitalization for acute COVID-19, were retrospectively analyzed with 80 having comprehensive mapping of organ involvement. Results: The average time between acute episode and post-COVID-19 care was 149 days. Spirometry indicated significant abnormalities in lung function. Predominant symptoms included respiratory (75%), fatigue (73%), neurological (62.5%), and ear-nose-throat issues (51.25%). Multiorgan dysfunctions were observed in 87.5% of patients, contributing to an 18.33% reduction in health quality compared to pre-acute COVID-19 levels. Subgroup analysis identified four distinct post-COVID-19 syndrome subgroups, highlighting the coexistence of respiratory and neurological disorders as potential indicators and drivers of further organ involvement. Our results reveal that most patients with post-COVID-19 syndrome suffer from multiorgan disorders. Conclusions: The presence of coexisting respiratory and neurological symptoms suggests the involvement of other organ systems as well. The complexity of multiorgan involvement requires further studies to provide insights into the different symptom clusters and identify potential targets for personalized preventive and therapeutic interventions to improve patient outcome.

RevDate: 2024-04-09

Jangnin R, Ritruangroj W, Kittisupkajorn S, et al (2024)

Long-COVID Prevalence and Its Association with Health Outcomes in the Post-Vaccine and Antiviral-Availability Era.

Journal of clinical medicine, 13(5): pii:jcm13051208.

Background and Objectives: After recovering from COVID-19, patients may experience persistent symptoms, known as post-COVID-19 syndrome or long COVID, which include a range of continuing health problems. This research explores the prevalence, associated factors, and overall health outcomes of long COVID during a period of extensive vaccination and antiviral treatment availability in Thailand. Materials and Methods: This observational study involved 390 adult patients with COVID-19 between January and March 2022. Beginning three months after their diagnosis, these patients were interviewed via telephone every three months for a period of one year. The data collection process included gathering demographic information and administering a standardized questionnaire that addressed the patients' physical condition following COVID-19, their mental health, sleep disturbances, and overall quality of life. Results: The cohort consisted of 390 participants, with an average age of 31.8 ± 13.6. Among them, 96.7% (n = 377) were vaccinated, and 98.2% (n = 383) underwent antiviral treatment. Long-COVID prevalence was observed at 77.7%, with the most frequently reported symptoms being fatigue (64.1%) and cough (43.9%). Regarding mental health, depression was reported by 8.2% of the participants, anxiety by 4.1%, and poor sleep quality by 33.3%. Advanced statistical analysis using multivariable logistic regression showed significant links between long-COVID symptoms and patients aged below 60 (p = 0.042), as well as the initial symptom of cough (p = 0.045). In the subset of long-COVID sufferers, there was a notable correlation in females with symptoms such as headaches (p = 0.001), dizziness (p = 0.007), and brain fog (p = 0.013). Conclusions: Despite the extensive distribution of vaccines and antiviral therapies, the prevalence of long COVID remains high, being associated particularly with individuals under 60 and those exhibiting a cough as an early symptom. The study further reveals that mental health issues related to long COVID are profound, going beyond the scope of physical symptomatology.

RevDate: 2024-04-09

Kikinis Z, Castañeyra-Perdomo A, González-Mora JL, et al (2024)

Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19.

Frontiers in psychiatry, 15:1337888.

Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.

RevDate: 2024-04-09

Estebanez-Pérez MJ, Martín-Valero R, Pastora-Estebanez P, et al (2024)

Experiences of people with Long Covid with a digital physiotherapy intervention: A qualitative study.

Health expectations : an international journal of public participation in health care and health policy, 27(2):e13993.

PURPOSE: Long Covid syndrome is a multiorgan condition with multiple sequelae affecting quality of life, capacity to work and daily activities. The advantages that new technologies can offer are presented as an opportunity in the current healthcare framework.

OBJECTIVE: This research aimed to explore people with Long Covid's experiences with a digital physiotherapy practice intervention, during four weeks.

METHODS: Qualitative semistructured interviews were conducted by video call. Thirty-two Long Covid participants were invited to join an in-depth interview once the intervention was completed. Participants were queried on their intervention experiences and perceptions, as well as any lifestyle changes made, as a result of receiving digital physiotherapy practice. The interviews were transcribed and analysed using inductive qualitative content analysis.

RESULTS: In-depth qualitative analysis has revealed four themes that reflect participants' perceptions of digital physiotherapy intervention. The helpfulness of the exercises, interaction with the physiotherapist, the domestic use of technology and the future of digital health practice were the topics highlighted by Long Covid participants. Some improvements have been suggested including video sounds and the need to introduce face-to-face sessions. Participants stated that interventions were helpful and superior to printed exercise sheets, mobile phone apps and usual care received. This intervention did not present major barriers, highlighting the importance of personalized care and continuity in the provision of health services.

CONCLUSION: The digital physiotherapy practice is perceived by people with Long Covid as an appropriate method for the care of their health needs. Participants stated the need for this type of intervention in the public health system, where it would eliminate waiting lists, facilitate accessibility and improve existing care.

Participants contributed to the interpretation of the data acquired in the interview.

CLINICAL TRIAL REGISTRATION: Trial registration NCT04742946.

RevDate: 2024-04-09

Liew F, Efstathiou C, Fontanella S, et al (2024)

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

Nature immunology, 25(4):607-621.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood[1]. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

RevDate: 2024-04-08

Ceglarek L, O Boyman (2024)

Immune dysregulation in long COVID.

Nature immunology [Epub ahead of print].

RevDate: 2024-04-08

Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, et al (2024)

Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI.

The American journal of medicine pii:S0002-9343(24)00216-X [Epub ahead of print].

PURPOSE: Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

METHODS: Magnetic resonance spectroscopy (MRS) data was acquired with a 3T Prisma MRI scanner. We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n=17), ME/CFS (n=17), and healthy controls (n=10) using Osprey software. The statistical analyses were performed using SPSS version 29. Age and sex were included as nuisance covariates.

RESULTS: Glutamate levels were significantly higher in long COVID (p=0.02) and ME/CFS (p=0.017) than in healthy controls. No significant difference was found between the two patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (p=0.012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

CONCLUSION: Our study identified significantly elevated Glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the two patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

RevDate: 2024-04-08

Stave GM, Nabeel I, Q Durand-Moreau (2024)

Long COVID-ACOEM Guidance Statement.

Journal of occupational and environmental medicine, 66(4):349-357.

Persistent symptoms are common after acute COVID-19, often referred to as long COVID. Long COVID may affect the ability to perform activities of daily living, including work. Long COVID occurs more frequently in those with severe acute COVID-19. This guidance statement reviews the pathophysiology of severe acute COVID-19 and long COVID and provides pragmatic approaches to long COVID symptoms, syndromes, and conditions in the occupational setting. Disability laws and workers' compensation are also addressed.

RevDate: 2024-04-08

Appel KS, Nürnberger C, Bahmer T, et al (2024)

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

Infection [Epub ahead of print].

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score.

METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L).

RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001).

CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities.

TRAIL REGISTRATION NUMBER: The cohort is registered at www.

CLINICALTRIALS: gov under NCT04768998.

RevDate: 2024-04-08

Sviercz F, Jarmoluk P, Godoy Coto J, et al (2024)

The abortive SARS-CoV-2 infection of osteoclast precursors promotes their differentiation into osteoclasts.

Journal of medical virology, 96(4):e29597.

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory system, the impact of COVID-19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS-CoV-2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte-derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS-CoV-2 strains heightened osteoclast formation in a dose-dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS-CoV-2 induced early pro-inflammatory M1 macrophage polarization, shifting toward an M2-like profile. Osteoclastogenesis-related genes (RANK, NFATc1, DC-STAMP, MMP9) were upregulated, and surprisingly, SARS-CoV-2 variants promoted RANKL-independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS-CoV-2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID-19.

RevDate: 2024-04-08

Taylor SA, NJ Smyth (2024)

COVID-19 and the Postviral Syndrome of Long COVID: Where We Have Come from and Where We Are Going.

Health & social work pii:7642046 [Epub ahead of print].

RevDate: 2024-04-08

Tanking C, Lakkananurak C, Srisakvarakul C, et al (2024)

Postural orthostatic tachycardia syndrome and other autonomic dysfunctions following COVID-19: Incidence, characteristics, and associated factors.

Journal of arrhythmia, 40(2):230-236.

BACKGROUND: Long-COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction, especially postural orthostatic tachycardia syndrome (POTS) following COVID-19. However, there is a lack of information regarding the incidence and associated factors in Asian population.

METHODS: A retro-prospective study was conducted to evaluate patients with symptoms suggestive of POTS or other autonomic dysfunctions. These symptoms last at least 3 months after PCR-proven COVID-19. Exclusion criteria were age under 18 years old, pregnancy, and pre-COVID-19 autonomic dysfunction symptoms. Patients with a symptom severity score greater than two were assessed with blood tests, 24-h Holter, 24-h ambulatory blood pressure, echocardiogram, and head-up tilt table (HUTT).

RESULTS: Seven hundred ninety-three patients were interviewed at 146 ± 37 days after COVID-19. The majority of patients were middle-aged females (53%). Of those, 15 patients had the symptom severity score greater than 2. Out of those 15 patients, 12 had positive HUTT (1 demonstrating POTS, 10 neurocardiogenic syncope, and 1 orthostatic hypotension). Among those with positive HUTT patients, C-reactive protein (CRP) was significantly higher (OR 1.01; p-value 0.041). Fatigue and dyspnea on exertion were the two most complaint symptoms.

CONCLUSIONS: This study shows the incidence of autonomic dysfunction and POTS is 1.5% (12/793) and 0.1% POTS (1/793), respectively, in a primary care setting (among general post-COVID-19 patients). The most common symptoms for these patients were fatigue and dyspnea.

RevDate: 2024-04-08

Chaudhry D, Khandelwal S, Bahadur C, et al (2024)

Prevalence of long COVID symptoms in Haryana, India: a cross-sectional follow-up study.

The Lancet regional health. Southeast Asia, 25:100395.

BACKGROUND: Emerging research indicates growing concern over long COVID globally, although there have been limited studies that estimate population burden. We aimed to estimate the burden of long COVID in three districts of Haryana, India, using an opportunity to link a seroprevalence study to follow-up survey of symptoms associated with long COVID.

METHODS: We used a population-based seroprevalence survey for COVID-19 conducted in September 2021 across Haryana, India. Adults from three purposively selected districts (Rohtak, Gurugram, and Jhajjar) were eligible to participate; 2205 of 3213 consented to participate in a survey on health status. Trained investigators administered a structured questionnaire that included demographic characteristics, self-reported symptoms of illness in the last six months before the survey, mental health, and history of COVID-19.

FINDINGS: Unadjusted regression estimates indicated positive correlations between symptomatic complaints and COVID-19 exposure, suggesting lingering effects of COVID-19 in this population. The overall physical morbidity index was higher among those who tested positive for COVID-19, as was the incidence of new cases. However, both morbidity and incidence became statistically insignificant after adjustment for multiple comparisons. Cough emerged as the only statistically significant individual persistent symptom. Sex-stratified analyses indicated significant estimates only for physical morbidity in women.

INTERPRETATION: This study is one of the first from India that uses a large population-based sample to examine longer term repercussions of COVID infections. The burden of long COVID should primarily be addressed in clinical settings, where specialised treatment for individual cases continues to evolve. Our analyses also provide insight into the size and nature of studies required to assess the population-level burden of long COVID.

FUNDING: This paper was produced under the auspices of the Lancet COVID 19 Commission India Task Force, which was supported financially by the Reliance Foundation. The Lancet COVID 19 Commission was set up in July 2020 and submitted its final report by October 2022. This report by the India Task Force was prepared during the same period.

RevDate: 2024-04-08

Chen Y, Zhang D, Zhang B, et al (2024)

Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program.

Research square pii:rs.3.rs-4151744.

Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.

RevDate: 2024-04-08

Padilla S, Ledesma C, García-Abellán J, et al (2024)

Long COVID across SARS-CoV-2 variants, lineages, and sublineages.

iScience, 27(4):109536.

This prospective study aimed to determine the prevalence of long COVID in patients hospitalized for SARS-CoV-2 infection from March 2020 to July 2022 and assess the impact of different viral lineages. A total of 2,524 patients were followed up for 12 months, with persistent symptoms reported in 35.2% at one month, decreasing thereafter. Omicron variant patients initially showed higher symptom intensity, but this trend diminished over time. Certain viral lineages, notably Delta lineages AY.126 and AY.43, and Omicron sublineages BA.1.17, BA.2.56, and BA.5.1, consistently correlated with more severe symptoms. Overall, long COVID prevalence and severity were similar across SARS-CoV-2 variants. Specific lineages may influence post-COVID sequelae persistence and severity.

RevDate: 2024-04-07

Benito-León J, Lapeña J, García-Vasco L, et al (2024)

Exploring Cognitive Dysfunction in Long COVID Patients: Eye Movement Abnormalities and Frontal-Subcortical Circuits Implications via Eye-Tracking and Machine Learning.

The American journal of medicine pii:S0002-9343(24)00217-1 [Epub ahead of print].

BACKGROUND: Cognitive dysfunction is regarded as one of the most severe aftereffects following coronavirus disease 2019 (COVID-19). Eye movements, controlled by various brain regions, including the dorsolateral prefrontal cortex and frontal-thalamic circuits, offer a potential metric for evaluating cognitive dysfunction. We aimed to examine the utility of eye movement measurements in identifying cognitive impairments in long COVID patients.

METHODS: We recruited 40 long COVID patients experiencing subjective cognitive complaints and 40 healthy controls and used a certified eye-tracking medical device to record saccades and antisaccades. Machine learning was applied to enhance the analysis of eye movement data.

RESULTS: Patients did not differ from the healthy controls regarding age, sex, and years of education. However, the patients' Montreal Cognitive Assessment total score was significantly lower than healthy controls. Most eye movement parameters were significantly worse in patients: the latencies, gain, and velocity of visually and memory-guided saccades, the number of correct memory saccades, the latencies and duration of reflexive saccades, and the number of errors in the antisaccade test. Machine learning permitted distinguishing between long COVID patients experiencing subjective cognitive complaints and healthy controls.

CONCLUSION: Our findings suggest impairments in frontal subcortical circuits in long COVID patients experiencing subjective cognitive complaints. Eye-tracking, combined with machine learning, offers a novel, efficient way to assess and monitor long COVID patients' cognitive dysfunctions, suggesting its utility in clinical settings for early detection and personalized treatment strategies. Further research is needed to determine the long-term implications of these findings and the reversibility of cognitive dysfunctions.

RevDate: 2024-04-08

Hylton H, Long A, Francis C, et al (2022)

Real-world use of the Breathing Pattern Assessment Tool in assessment of breathlessness post-COVID-19.

Clinical medicine (London, England), 22(4):376-379.

INTRODUCTION: Breathing pattern disorders (BPDs) are a common cause of chronic breathlessness, including after acute respiratory illnesses such as COVID pneumonia. BPD is however underdiagnosed, partly as a result of difficulty in clinically assessing breathing pattern. The Breathing Pattern Assessment Tool (BPAT) has been validated for use in diagnosing BPD in patients with asthma but to date has not been validated in other diseases.

METHODS: Patients undergoing face-to-face review in a post-COVID clinic were assessed by a respiratory physician and specialist respiratory physiotherapist. Assessment included a Dyspnoea-12 (D12) questionnaire to assess breathlessness, physiotherapist assessment of breathing pattern including manual assessment of respiratory motion, and BPAT assessment. The sensitivity and specificity of BPAT for diagnosis of BPD in post-COVID patients was assessed.

RESULTS: BPAT had a sensitivity of 89.5% and specificity of 78.3% for diagnosing BPD in post-COVID breathlessness. Patients with a BPAT score above the diagnostic cut-off had higher levels of breathlessness than those with lower BPAT scores (D12 score mean average 19.4 vs 13.2).

CONCLUSION: BPAT has high sensitivity and moderate specificity for BPD in patients with long COVID. This would support its use as a screening test in clinic, and as a diagnostic tool for large cohort studies.

RevDate: 2024-04-05

Simpson SA, Evans RA, Gilbert HR, et al (2024)

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial.

BMJ open, 14(4):e083255 pii:bmjopen-2023-083255.

INTRODUCTION: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes.

METHODS AND ANALYSIS: A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention.

ETHICS AND DISSEMINATION: The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public.

TRIAL REGISTRATION NUMBER: ISRCTN68786622.

PROTOCOL VERSION: 2.0 (16 May 2023).

RevDate: 2024-04-05

Imeri G, Conti C, Caroli A, et al (2024)

Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component.

Multidisciplinary respiratory medicine, 19:.

BACKGROUND: There are uncertainties whether the impairment of lung diffusing capacity in COVID-19 is due to an alteration in the diffusive conductance of the alveolar membrane (Dm), or an alteration of the alveolar capillary volume (Vc), or a combination of both. The combined measurement DLNO and DLCO diffusion, owing to NO higher affinity and faster reaction rate with haemoglobin compared to CO, enables the simultaneous and rapid determination of both Vc and Dm. The aim of the present study was to better identify the precise cause of post-COVID-19 diffusion impairment.

METHODS: Using the combined NO and CO gas transfer techniques (DLNO and DLCO), it is possible to better understand whether gas exchange abnormalities are due to membrane or alveolar capillary volume components. The present study was aimed at evaluating pulmonary gas exchange one year after severe COVID-19.  Results: The cohort included 33 survivors to severe COVID-19 (median age 67 years, 70% male) with no pre-existing lung disease, who underwent clinical, lung function and imaging assessments at 12 months due to persistence of respiratory symptoms or radiological impairment. The gas exchange abnormalities were mainly determined by the compromise of the vascular component as demonstrated by vascular pattern of gas exchange impairment (i.e., DLNO/DLCO≥110%, 76% of the sample), and by a reduction of the Vc (73%), while the Dm was reduced only in 9% of the entire sample. We did not find a correlation between the gas exchange impairment and the extent of the chest CT alterations (DLCO p = 0.059 and DLNO p = 0.054), which on average were found to be mild (11% of the parenchyma).

CONCLUSION: In COVID-19 survivors who are still symptomatic or have minimal CT findings at one year, gas exchange abnormalities are determined by impairment of the vascular component, rather than the diffusive component of the alveolar membrane.

RevDate: 2024-04-05

Marcilla-Toribio I, Moratalla-Cebrián ML, Notario-Pacheco B, et al (2024)

Gender differences in symptomatology, socio-demographic information and quality of life in Spanish population with long COVID condition: a cross-sectional study.

Frontiers in public health, 12:1355973.

INTRODUCTION: Long COVID patients experience a decrease in their quality of life due to the symptomatology produced by the disease. It is also important to understand how long COVID affects both men and women. The objective of this study is to examine the impact of long COVID symptomatology on the quality of life of Spanish adults from a gender perspective.

METHODS: An observational and cross-sectional study was carried out. Participants were able to complete an online questionnaire using an online platform. A sample of 206 people participated in the study.

RESULTS: The 80.6% of the sample were women with a mean age of 46.51 (±8.28) and the 19.4% were men with a mean age of 48.03 (±9.50). The medium score in the PAC19-QoL test was 141.47 (±24.96) and segmented by gender, 141.65 (±23.95) for women and 140.82 (±28.66) for men. The most common symptoms in women were muscle and joint pain (94.6%), fatigue (94.0%), discomfort (92.2%), difficulty concentrating (91.0%), and memory loss (88.6%). For men the symptoms included muscle and joint pain (97.5%) and fatigue (97.5%) both occupying first position, discomfort (92.0%), difficulty concentrating (90.0%), mood disturbances (90.0%), and memory loss (87.5%). The chi-square test showed statistical significance (p < 0.005) for socio-demographic information, quality of life scores, and long COVID symptoms by intensities.

CONCLUSION: This study shows that there are gender differences in the way that long COVID is experienced.

RevDate: 2024-04-05

Wang Y, Guo L, Cui D, et al (2024)

Immune Responses in Discharged COVID-19 Patients With and Without Long COVID Symptoms.

Open forum infectious diseases, 11(4):ofae137.

The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)-immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a "one-size-fits-all" approach to future treatment modalities.

RevDate: 2024-04-05

Peng Z, Zheng Y, Yang Z, et al (2024)

Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.

Frontiers in medicine, 11:1341072.

BACKGROUND: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management.

OBJECTIVES: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety.

MATERIALS AND METHODS: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes.

RESULTS: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22).

CONCLUSION: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.

RevDate: 2024-04-04

Kabir MF, Yin KN, Jeffree MS, et al (2024)

Clinical presentation of post-COVID pain and its impact on quality of life in long COVID patients: a cross-sectional household survey of SARS-CoV-2 cases in Bangladesh.

BMC infectious diseases, 24(1):375.

BACKGROUND: Pain is one of the prevalent Long COVID Symptoms (LCS). Pain interferes with the quality of life (QoL) and induces disease burden.

PURPOSE: The study aimed to elicit the clinical presentation of pain and determine the relationships between QoL and pain in LCS.

METHODS: This household cross-sectional study of 12,925 SARS-CoV-2 cases between July and December 2021 was carried out in eight administrative divisions of Bangladesh. Stratified random sampling from the cases retrieved from the Ministry of Health was employed. Symptom screening was performed through COVID-19 Yorkshire Rehabilitation Scale, and long COVID was diagnosed according to World Health Organization (WHO) criteria. The analyses were conducted using IBM SPSS (Version 20.00).

RESULTS: The prevalence of pain in long COVID was between 01 and 3.1% in the studied population. The study also found five categories of pain symptoms as LCS in Bangladesh: muscle pain 3.1% (95% CI; 2.4-3.8), chest pain 2.4% (95% CI; 1.8-3.1), joint pain 2.8% (95% CI; 2.2-2.3), headache 3.1% (95% CI; 2.4-3.8), and abdominal pain 0.3% (95% CI; 0.01-0.5). People with LCS as pain, multiple LCS, and longer duration of LCS had significantly lower quality of life across all domains of the WHOQOL-BREF (P < 0.001) compared to asymptomatic cases.

CONCLUSION: Three out of ten people with long COVID experience painful symptoms, which can significantly reduce their quality of life. Comprehensive rehabilitation can improve the symptoms and reduce the burden of the disease.

RevDate: 2024-04-04

Tindle R (2024)

Long COVID: Sufferers can take heart.

Australian journal of general practice, 4(4):238-240.

RevDate: 2024-04-04

Michael HU, Brouillette MJ, Fellows LK, et al (2024)

Medication Utilization Patterns in Patients with Post-COVID Syndrome (PCS): Implications for Polypharmacy and Drug-Drug Interactions.

Journal of the American Pharmacists Association : JAPhA pii:S1544-3191(24)00103-1 [Epub ahead of print].

BACKGROUND: Post-COVID syndrome (PCS) causes lasting symptoms like fatigue and cognitive issues. PCS treatment is non-specific, focusing on symptom management, potentially increasing the risk of polypharmacy.

OBJECTIVES: To describe medication use patterns among patients with Post-COVID Syndrome (PCS) and estimate the prevalence of polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden.

METHODS: A cross-sectional analysis of baseline data from the Quebec Action for Post-COVID cohort, consisting of individuals self-identifying with persistent COVID-19 symptoms beyond 12 weeks. Medications were categorized using Anatomical Therapeutic Classification (ATC) codes. Polypharmacy was defined as using five or more concurrent medications. The Anticholinergic and Sedative Burden Catalog assessed anticholinergic and sedative loads. The Lexi-Interact checker identified potential drug-drug interactions, which were categorized into three severity tiers.

RESULTS: Out of 414 respondents, 154 (average age 47.7 years) were prescribed medications related to persistent COVID-19 symptoms. Drugs targeting the nervous system were predominant at 54.5%. The median number of medications was 2, while 11.7% reported polypharmacy. Over half of the participants prescribed medications used at least one anticholinergic or sedative medication, and 25% had the potential risk for clinically significant drug-drug interactions, primarily needing therapy monitoring.

CONCLUSIONS: Our study reveals prescription patterns for PCS, underscoring the targeted management of nervous system symptoms. The risks associated with polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden stress the importance of judicious prescribing. While limitations like recall bias and a regional cohort are present, the findings underscore the imperative need for vigilant PCS symptom management.

RevDate: 2024-04-04

Saheb Sharif-Askari F, Ali Hussain Alsayed H, Saheb Sharif-Askari N, et al (2024)

Risk factors and early preventive measures for long COVID in non-hospitalized patients: analysis of a large cohort in the United Arab Emirates.

Public health, 230:198-206 pii:S0033-3506(24)00102-1 [Epub ahead of print].

OBJECTIVES: Long COVID is characterized by persistent symptoms lasting for 4 weeks or more following the acute infection with SARS-CoV-2. Risk factors for long COVID and the impact of pre-COVID vaccination and treatment during acute COVID-19 remain uncertain. This study aimed to investigate patient-specific factors associated with long COVID in a large cohort of non-hospitalized adult patients with mild to moderate COVID-19 in Dubai.

STUDY DESIGN: Cohort study.

METHODS: The study included 28,375 non-hospitalized adult patients diagnosed with mild to moderate COVID-19 between January 1, 2021, and September 31, 2022, in Dubai, who were followed up for 90 days. The presence of long COVID symptoms was documented by physicians during patient visits to the family medicine department. Furthermore, long COVID-related risk factors were collected and analyzed, including patient demographics, comorbidities, pre-COVID vaccination status, and the COVID-related treatments received during the acute phase of the illness. Cox proportional hazard models were applied for the statistical analysis.

RESULTS: Among the cohort, 2.8% of patients experienced long COVID symptoms during the 90-day follow-up. Patients with long COVID tended to be younger, female, and of Caucasian race. Common symptoms included fatigue, muscle pain, respiratory symptoms, abdominal and neurological symptoms, allergic reactions, skin rashes, and hair loss. Risk factors for long COVID were identified as diabetes mellitus, asthma, and Vitamin D deficiency. Females and Caucasians had a higher risk of long COVID during the pre-Omicron period compared to the Omicron period. Pre-COVID vaccination was associated with a reduced risk of long COVID in all patient subgroups. Treatment with favipiravir or sotrovimab during the acute phase of COVID-19 was linked to a decreased risk of long COVID, although favipiravir showed limited effectiveness in the high-risk group.

CONCLUSION: This study contributes to the existing knowledge by identifying risk factors for long COVID among non-hospitalized patients and emphasizing the potential benefits of pre-COVID vaccination and timely treatment.

RevDate: 2024-04-04

Stern R, Bibi M, MD Keltz (2024)

Premature Ovarian Insufficiency After Coronavirus Disease 2019 (COVID-19): Autoimmune Follicle-Stimulating Hormone (FSH) and FSH Receptor Blockade.

Obstetrics and gynecology [Epub ahead of print].

BACKGROUND: Since the onset of the coronavirus disease (COVID-19) pandemic, a variety of long-COVID-19 symptoms and autoimmune complications have been recognized.

CASES: We report three cases of autoimmune premature poor ovarian response in patients aged 30-37 years after mild to asymptomatic COVID-19 before vaccination, with nucleotide antibody confirmation. Two patients failed to respond to maximum-dose gonadotropins for more than 4 weeks, despite a recent history of response before having COVID-19. After a month of prednisone 30 mg, these two patients had normal follicle-stimulating hormone (FSH) levels, high oocyte yield, and blastocyst formation in successful in vitro fertilization cycles. All three patients have above-average anti-müllerian hormone levels that persisted throughout their clinical ovarian insufficiency. Two patients had elevated FSH levels, perhaps resulting from FSH receptor blockade. One patient, with a history of high response to gonadotropins 75 international units per day and below-normal FSH levels, had no ovarian response to more than a month of gonadotropins (525 international units daily), suggesting autoimmune block of the FSH glycoprotein and possible FSH receptor blockade.

CONCLUSION: Auto-antibody production in response to COVID-19 before vaccination may be a rare cause of autoimmune poor ovarian response. Although vaccination is likely protective, further study will be required to evaluate the effect of vaccination and duration of autoimmune FSH or FSH receptor blockade.

RevDate: 2024-04-04

Ebell MH (2024)

Cognitive Behavior Therapy Effective in Patients With Fatigue Associated With Long COVID.

American family physician, 109(3):Online.

RevDate: 2024-04-04

Yang H, Guan L, Yang T, et al (2024)

Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.

Journal of medical virology, 96(4):e29566.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

RevDate: 2024-04-04

Hu K, L Zhang (2024)

Challenges and Opportunities Associated with Lifting the Zero COVID-19 Policy in China.

Exploratory research and hypothesis in medicine, 9(1):71-75.

Chinese government lifted its "Zero COVID-19" policy in December 2022. The estimated COVDI-19 new cases and deaths after the policy change are 167-279 million (about 12.0% to 20.1% of the Chinese population) and 0.68-2.1 million, respectively. Recent data also revealed continuous drops in fertility rate and historically lowest growth in gross domestic production in China. Thus, balancing COVID-19 control and economic recovery in China is of paramount importance yet very difficult. Supply chain disruption, essential service reduction and shortage of intensive care units have been discussed as the challenges associated with lifting "Zero COVID-19" policy. The additional challenges may include triple epidemic of COVID-19, respiratory syncytial virus and influenza, mental health issues of healthcare providers, care givers and patients, impact on human mobility, lack of robust genomic and epidemiological data and long COVID-19. However, the policy-associated opportunities and other challenges are largely untouched, but warrant attention of and prompt reactions by the policy makers, healthcare providers, public health officials and other stakeholders. The associated benefits are quick reach of herd immunity, boost of economy and businesses activities and increase in social activities. At this moment, we must embrace the policy change, effectively mitigate its associated problems and timely and effectively maximize its associated benefits.

RevDate: 2024-04-04

Marques FRDM, Laranjeira C, Carreira L, et al (2024)

Managing long COVID symptoms and accessing health services in Brazil: A grounded theory analysis.

Heliyon, 10(7):e28369.

BACKGROUND: The worldwide community has shown significant interest in researching the management of Long COVID. However, there is scarce evidence about the daily experiences of people living with Long COVID and their insights into the healthcare services provided to them.

AIMS: This study aims to understand the experience of Long COVID sufferers with their symptoms and in accessing health services.

METHOD: We employed Charmaz's grounded theory methodology, informed by constructivism, and applied the COREQ guidelines for qualitative research. Sixty-six Brazilians living with Long COVID participated in the study. The data was collected using semi-structured telephone interviews and analyzed using a constant comparative process.

FINDINGS: The findings refer firstly to the consequences of persistent Long COVID symptoms. Secondly, they describe how the disease trajectory required Long COVID sufferers to reorganize their routines and develop adaptive strategies. Lastly, they reflect a diverse array of both positive and negative interactions inside the healthcare system conveyed by individuals suffering from Long COVID. These elements converge towards the core category of the study: "The limbo of Long COVID sufferers: between the persistence of symptoms and access to health services".

CONCLUSIONS: Long COVID is characterized by its varied nature, including a range of physical and emotional repercussions experienced by individuals. There is a need for enhanced comprehension and discourse about Long COVID across several domains, including the general public, policy-making entities, and healthcare professionals. In this sense, the development of specialized services or the reinforcement of existing services to support long COVID sufferers is imperative.

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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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Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

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