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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 27 Jun 2026 at 01:53 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"[TIAB] ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2026-06-25

Yang S, Wen X, Lin Y, et al (2026)

Expression levels of SARS-CoV-2 IgM, IgG, and neutralizing antibodies in a Chinese cohort and detection of peptide-specific antibodies in COVID-19 patients.

BMC infectious diseases pii:10.1186/s12879-026-13532-y [Epub ahead of print].

BACKGROUND: Long COVID is a complex multisystem disorder affecting approximately 65 million individuals worldwide, with autoimmune mechanisms implicated in its pathogenesis. This study aimed to elucidate the role of SARS-CoV-2-induced autoantibodies and immune dysregulation in the development of Long COVID, focusing specifically on autoimmunity and aberrant immune activation. The investigation sought to explore the underlying mechanisms through serological and peptide-based analyses.

METHODS: Serum samples from 315 healthcare workers, serving as a control cohort, were analyzed for the presence of SARS-CoV-2 IgM, IgG, and Neutralizing Antibodies (NAbs), with stratification based on age, gender, vaccination timing, and symptom clusters. Bioinformatic approaches were employed to identify SARS-CoV-2 epitopes with homology to human proteins, screening for epitopes of the SARS-CoV-2 Spike (S) and Nucleocapsid (N) proteins and their human homologous peptides through analyses of hydrophilicity, antigenicity, and homology prediction. An ELISA-based method was utilized to detect antibody responses to these peptides in both COVID-19 infected groups (categorized as mild, moderate, or severe) and an uninfected group.

RESULTS: The primary findings indicated a high seropositivity rate for IgG (97%) and Neutralizing Antibodies (94%) among the control group, with notable age-related trends: IgM levels increased with age, whereas IgG and Neutralizing Antibodies showed a decline. Female participants demonstrated higher IgG levels compared to their male counterparts. Antibody levels did not exhibit significant differences across acute or persistent symptom clusters (≥ 6 months post-infection). However, neurological symptoms, whether acute or chronic, were associated with elevated IgG and Neutralizing Antibody titers, suggesting that neurotropic infections may elicit a more robust humoral immune response. Bioinformatic analyses identified 29 potential epitopes within the S protein and 10 within the N protein, with 91 and 24 human homologous peptides, respectively. The detection of peptide-specific antibodies in the serum of the COVID-19 infected group revealed that antibodies against eight peptides displayed a greater than 2.5-fold difference between the COVID-19-infected and uninfected groups.

CONCLUSION: These findings underscore age- and gender-related variations in antibody responses, identify immunodominant peptides with potential implications for COVID-19 symptoms, and suggest that cross-reactive antibodies targeting viral-human homologous peptides (e.g., S68-CHL1) may play a role in autoimmune mechanisms associated with COVID-19.

TRIAL REGISTRATION: Clinical trial number: Not applicable.

RevDate: 2026-06-26

Chambers PW (2026)

Magnesium and gender in long COVID.

Journal of translational medicine, 24(1):.

RevDate: 2026-06-26

Kumar N, Khandavalli N, Avedissian SN, et al (2026)

Translational insights into Long-COVID: evaluation of preclinical animal models along the lung-brain-immune axis with focus on Golden Syrian Hamsters.

Journal of neuroinflammation pii:10.1186/s12974-026-03928-7 [Epub ahead of print].

Long-COVID, also referred to as post-acute sequelae of COVID-19 (PASC), is a heterogeneous disorder encompassing more than 200 reported symptoms that commonly affect the respiratory and nervous systems. Emerging clinical evidence indicates that unresolved lung inflammation, vascular injury, and immune dysregulation drive sustained neuroinflammation and impaired neurocognitive function in Long-COVID patients. Given the ethical and logistical constraints of human studies, biologically relevant animal models are essential for understanding the mechanisms and for evaluating therapeutic strategies against Long-COVID. In this review, we synthesize current evidence from preclinical animal models of Long-COVID, with a particular emphasis on the Golden Syrian Hamsters. Golden Syrian Hamsters are naturally susceptible to SARS-CoV-2 infection without the need for genetic modification and recapitulate key features of human disease, including robust viral replication, pulmonary pathology, and inflammatory response during acute infection. Importantly, accumulating evidence demonstrates that Golden Syrian Hamsters develop persistent post-acute abnormalities along the lung-brain-immune axis, including impaired alveolar repair, fibrotic lung remodeling, neuroinflammation, viral or antigen persistence, and behavioral alterations that parallel core features of Long-COVID. We compare the strengths and limitations of Golden Syrian Hamsters with other commonly used pre-clinical animal models including mice, and non-human primates, highlighting differences in translational relevance, feasibility, and ability to model chronic lung-brain-immune axis dysfunction. While there are limitations, particularly regarding limited availability of immunological reagents and validated cognitive and behavioral assays, the Golden Syrian Hamsters offers a balanced and accessible platform for mechanistic studies of PASC. Overall, this review positions Golden Syrian Hamster as a robust translational model for investigating lung-brain-immune axis pathology in Long-COVID and for advancing the development of targeted therapeutic interventions.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Donchev D, Nikolova R, Vaseva K, et al (2026)

Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome.

Biomedicines, 14(6): pii:biomedicines14061183.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited. Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores. Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H2 carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals. Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Malykh S, Demareva V, Malykh A, et al (2026)

Post-COVID-19 Consequences and Psychological Well-Being in Students: The Mediating Role of Trait Anxiety.

Behavioral sciences (Basel, Switzerland), 16(6): pii:bs16060996.

The long-term psychological consequences of COVID-19 remain insufficiently understood in student populations. This study examined the association between post-COVID-19 consequences and psychological functioning in university students, focusing on the mediating role of trait anxiety. A total of 7482 students aged 17 to 23 years completed an online survey assessing COVID-19 history, post-COVID-19 consequences, psychological well-being (WHO-5), subjective happiness (SHS), life satisfaction (SWLS), and trait anxiety (STAI). Participants were classified into three groups: no history of COVID-19, COVID-19 without post-COVID-19 consequences, and COVID-19 with post-COVID-19 consequences. Group differences were analyzed using ANOVA with Tukey post hoc tests, followed by regression and mediation analyses controlling for age and sex. Students reporting post-COVID-19 consequences showed higher trait anxiety and lower psychological well-being, subjective happiness, and life satisfaction than both comparison groups. Regression analyses indicated that poorer psychological functioning was associated specifically with post-COVID-19 consequences rather than COVID-19 history per se. Mediation analyses among previously infected students showed that trait anxiety statistically mediated these associations, accounting for 61% of the effect on psychological well-being, 84% on subjective happiness, and 68% on life satisfaction. These findings highlight trait anxiety as an important psychological factor statistically accounting for the association between post-COVID-19 consequences and reduced well-being.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Habuddha V, N Piya-Amornphan (2026)

Understanding the Impact of Long COVID on the Lives of Thai University Students.

International journal of environmental research and public health, 23(6): pii:ijerph23060687.

COVID-19 has had profound global impacts, and Long COVID may continue to affect quality of life and well-being in some individuals. Young adults may be particularly vulnerable to these impacts due to ongoing physiological, behavioral, and psychological development. This study aimed to examine the associations between Long COVID, mental health-related outcomes, and quality of life among university students. A total of 365 Thai undergraduate students participated in this cross-sectional study screening for Long COVID. Long COVID symptoms, mental health, sleep quality, and quality of life were assessed using validated Thai versions of the Long COVID Screening Questionnaire, DASS-21, PSQI, and EQ-5D-5L. Regression and group comparison analyses were conducted between participants with Long COVID and those without Long COVID. Fatigue and cough were the most reported symptoms, while sleep disturbances were also prevalent. Long COVID was associated with significantly lower quality of life scores (p = 0.035). However, no significant differences were observed in DASS-21 or PSQI scores between groups. Vaccination doses and prior COVID-19 infections differed significantly between groups (p < 0.001 and p = 0.017). These findings highlight the multisystem impacts of Long COVID and emphasize the importance of identification and supportive interventions to enhance student health and well-being.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Chen YH, Lin CH, Liu JH, et al (2026)

Association Between Prior NRICM101 Use and Response to Incentive Spirometer Training in Patients with Long COVID.

Healthcare (Basel, Switzerland), 14(12): pii:healthcare14121630.

Background: Inspiratory training using an incentive spirometer (IS) improves respiratory symptoms and functional status in Long COVID. In Taiwan, NRICM101 is commonly used during the acute phase; however, its impact on rehabilitation outcomes remains unclear. Objective: This study evaluated the effects of IS-based respiratory training and the potential influence of prior NRICM101 use. Methods: Participants were grouped by time since recovery, and pre-post changes after six weeks of IS training were compared between those with and without self-reported prior NRICM101 use. Primary outcomes were dyspnea and functional status; secondary outcomes included six-minute walk distance and arterial oxygen content. Results: IS training significantly improved dyspnea (p < 0.0001), functional status (p < 0.0001), and exercise endurance (NRICM101 group: p = 0.002; no NRICM101 group: p < 0.0001). Stratified analysis showed that when initiated within three months of recovery, participants without prior NRICM101 use had greater improvements in dyspnea (p < 0.0001), functional status (p = 0.001), and exercise endurance (p < 0.0001). Conclusions: Prior NRICM101 use may be associated with different rehabilitation patterns, likely reflecting differences in recovery trajectory or patient behavior rather than purely pharmacological effects.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Shahzad M, Siddiqui S, Lau C, et al (2026)

Symptom, Functional, and Work Participation Profiles Among Racialized Canadians with Pre-Existing Mental Health Challenges and Long COVID: A Cross-Sectional Study.

Healthcare (Basel, Switzerland), 14(12): pii:healthcare14121726.

BACKGROUND/OBJECTIVES: Long COVID is associated with persistent, multi-system symptoms, yet little is known about how it affects individuals with intersecting vulnerabilities, such as a racialized identity and pre-existing mental health conditions. This study aimed to descriptively characterize the symptom burden, functional outcomes and mental health in this population.

METHODS: A cross-sectional, exploratory study was conducted among 51 adults in Canada who self-identified as racialized and as having a pre-existing mental health condition and reported long COVID symptoms. Participants completed an online survey, including validated measures of symptoms, fatigue, post-exertional malaise, cognitive function, mental health and disability. Descriptive statistics were used to summarize outcomes.

RESULTS: Participants reported a slight to moderate overall symptom burden, with the highest scores in respiratory and psychological domains. Functional impairment was moderate across work, social and daily activities (Work and Social Adjustment Scale mean = 17.35; World Health Organization Disability Assessment Schedule 2.0 mean = 16.61; Post COVID-19 Functional Status Scale mean = 2.20). Fatigue and post-exertional malaise were notable (Modified Fatigue Impact Scale mean = 43.39; DePaul Symptom Questionnaire-Post-Exertional Malaise mean = 22.47), and cognitive difficulties were commonly reported (Perceived Deficits Questionnaire mean = 33.43). Anxiety and depression scores were in the mild to moderate range respectively (General Anxiety Disorder-7 mean = 9.27; Patient Health Questionnaire-9 mean = 11.43).

CONCLUSIONS: Clinically relevant fatigue, post-exertional malaise, and depression were found, alongside moderate functional limitations across life domains. The findings support the conceptualization of long COVID as a syndemic condition and underscore the need for equity-informed research, rehabilitation and public health strategies.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Churilov LP, Starshinova A, Kudryavtsev I, et al (2026)

Immunological Mechanisms and Machine Learning Applications in Post-COVID-19 Syndrome: A Narrative Review.

Microorganisms, 14(6): pii:microorganisms14061313.

UNLABELLED: Post-COVID-19 syndrome (PCS), also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), represents a heterogeneous set of persistent clinical manifestations developing after acute infection. These conditions are associated with immune dysregulation, autonomic imbalance, impaired thymic function, and possible viral persistence.

OBJECTIVE: This study aims to systematically synthesise current evidence on the immunopathogenesis of PCS and to critically evaluate the application of artificial intelligence (AI) and machine learning (ML) approaches for its prediction and clinical stratification.

METHODS: A PRISMA 2020-informed systematic review was conducted using PubMed/MEDLINE, Scopus, Web of Science, elibrary.ru and Embase databases (January 2020-December 2025). Studies addressing immunopathological mechanisms and AI/ML applications in PCS were selected based on predefined eligibility criteria. Risk of bias in prediction studies was assessed using the PROBAST tool. Due to heterogeneity, a structured qualitative synthesis was performed. Current evidence indicates that PCS may result from sustained systemic inflammation, cytokine dysregulation, autoimmunity, and delayed restoration of T-cell homeostasis, including reduced thymic output of naïve T lymphocytes. Persistent thymic dysfunction may contribute to prolonged immune imbalance, increased susceptibility to secondary infections, and reactivation of latent viruses. AI/ML approaches-including gradient boosting, ensemble learning, deep neural networks, and natural language processing-have demonstrated promising performance across multimodal datasets. However, significant limitations were identified, including small sample sizes, overfitting, lack of external validation, and heterogeneity in outcome definitions.

CONCLUSIONS: The integration of immunopathological insights with data-driven modelling highlights the potential of combined approaches for improving PCS risk stratification. However, current AI models remain insufficiently validated for clinical implementation. Future research should prioritise methodological standardisation, external validation, and incorporation of mechanistically informed biomarkers.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Khawandi J, Choaib A, Azzam M, et al (2026)

Echocardiogram Testing in Patients with Post-COVID-19 Condition: A Systematic Review and Meta-Analysis.

Journal of clinical medicine, 15(12): pii:jcm15124643.

Background: Post-COVID-19 condition (PCC) is a complication following acute COVID-19 infection, which may lead to long-term cardiac abnormalities. This review aimed to assess the prevalence of structural/functional deviations in echocardiography in individuals with PCC compared to patients without PCC. Methods: We searched three databases. Two reviewers independently screened articles using LASER Al and extracted relevant data using a piloted Excel sheet. We performed meta-analysis using OpenMeta and RevManWeb and a subgroup analysis based on patients' settings during acute COVID-19. We assessed the risk of bias using the Hoy et al. tool and the certainty using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 16 studies that reported on differences in echocardiographic findings in patients with or without PCC. Individuals with PCC were more likely to have structural/functional deviations in echocardiographic readings of unclear clinical significance, particularly those who were hospitalized during acute COVID-19. The overall certainty of the evidence was very low due to the high risk of bias, indirectness, and imprecision. Conclusions: This review provides insight into the use of echocardiograms and the frequency of test deviations in individuals with PCC. Despite existing evidence, there is a need for future studies to assess the diagnostic test accuracy of echocardiograms in PCC.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Diaconu IE, Onofrei MI, Vâță A, et al (2026)

Clinical and Inflammatory Predictors of Neurocognitive Decline in Long COVID: A Two-Year Longitudinal Study with Propensity Score Matching.

Medicina (Kaunas, Lithuania), 62(6): pii:medicina62061180.

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients' long-term quality of life. This study aimed to identify clinical and laboratory risk factors-including inflammatory markers and micronutrients-for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819-5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191-2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431-2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65-14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412-6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353-19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Suárez-Moreno N, Navarro-Matías E, Arroyo-Romero S, et al (2026)

Dietary Macronutrient Intake and Vascular Health in Patients with Long COVID: The BioICOPER Study.

Nutrients, 18(12): pii:nu18122028.

Background: Long COVID (LC) has been associated with persistent endothelial dysfunction and vascular impairment. Although nutrition is a key modifiable determinant of cardiovascular health, the relationship between dietary macronutrient intake and vascular alterations in LC remains poorly understood. Objective: To evaluate the association between dietary macronutrient intake and markers of vascular structure, arterial stiffness, and vascular aging in patients with LC, including potential sex differences. Methods: We conducted a cross-sectional study including 304 patients with LC. Dietary intake was assessed using a validated 7-day dietary record (EVIDENT study). Vascular evaluation included carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI), augmentation index adjusted to a heart rate of 75 beats per minute (AIx@75), and vascular aging index (VAI), measured using carotid ultrasound and validated devices (SphygmoCor[®] and VaSera[®]). Results: The mean age was 53 ± 12, higher in men (p = 0.001). The study included 207 women (68%) and 97 men (32%). Energy intake and carbohydrate intake in g/day showed a negative association with cfPWV in Model 2 (energy intake: β = -0.06; 95% CI: -0.11 to -0.01; p = 0.02; carbohydrate intake: β = -0.47; 95% CI: -0.87 to -0.07; p = 0.02). The percentage of carbohydrate/total energy intake was positively associated with AIx@75 in Model 2 (β = 0.8; 95% CI 0.12 to 1.49; p = 0.02), and percentage of fat/total energy intake showed a consistent inverse association (β = -0.30; 95% CI: -0.49 to -0.11; p = 0.002). No significant associations were observed for cIMT, baPWV, CAVI or VAI. Conclusions: In patients with LC, total energy intake and absolute carbohydrate intake were negatively associated with cfPWV, whereas the relative contribution of carbohydrates and fats to total energy intake showed divergent associations with AIx@75. These findings suggest that both absolute macronutrient intake and relative macronutrient distribution may be related to central arterial stiffness and wave reflection parameters LC. However, given the cross-sectional design of the study, these results should be interpreted as exploratory and do not allow causal inference. Further longitudinal and interventional studies are needed to confirm these findings and to assess whether nutritional strategies may contribute to modulating vascular risk in this population.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Schieffer B (2026)

Redefining pandemic resilience: a roadmap for post-infectious syndrome preparedness and health system transformation.

Frontiers in health services, 6:1779647.

Post-infectious syndromes like Long COVID and ME/CFS lead to disability and economic losses globally, especially in lower-income countries. These involve complex multisystem issues such as immune disturbances, inflammation, autonomic dysregulation, vascular problems, altered metabolism, and tissue damage. Re-infections increase the risk of disability and complications. Healthcare delays diagnosis and neglects long-term effects. We propose a three-part healthcare approach: primary care screening with digital tools, regional testing centers, and specialized Centers of Excellence for complex cases. An integrated infrastructure with registries, patient data, and wearables supports personalized care and surveillance. Policies should include disability benefits, rehab, infection control, and innovative funding. Healthcare must be accessible via mobile and community efforts, integrated into pandemic plans. The goal is to reduce morbidity and improve socioeconomic resilience.

RevDate: 2026-06-26
CmpDate: 2026-06-26

Williams SL, Beadle E, Williams P, et al (2026)

A mixed-methods analysis of the implementation of a new community long-COVID service during the 2020 pandemic: Learning from practice.

PloS one, 21(6):e0313367 pii:PONE-D-24-46697.

INTRODUCTION: The rapidly increasing prevalence of long-COVID (LC), a condition characterised by multisystem complexity and high patient symptom burden, posed an immediate need to develop new clinics for assessment and management. This article reports on the rapid implementation of a reactive and responsive LC care pathway. We mapped patients' journeys through this pathway, identifying the services that were activated according to prevalent symptoms, and used the Theoretical Domains Framework (TDF) to assess the barriers and facilitators to its implementation and delivery, from the perspective of health care professionals (HCPs) and LC patients.

METHODS: Mixed methods study, including retrospective quantitative cross-sectional analysis of patient data and semi-structured qualitative interviews. One hundred and sixteen patients who attended the long-COVID clinic in Hertfordshire, UK, in the first 5 months of its existence and consented for their data to be analysed. Six HCPs and five patients participated in semi-structured interviews.

RESULTS: Patients were referred into the service an average of 5.75 months post initial COVID-19 infection. 82% of patients required onward referral to other HCPs, most commonly pulmonary rehabilitation, chronic fatigue specialists, and a specialist COVID-19 rehab general practitioner embedded within the service. Patients reported having rehabilitation needs, moderate depression and anxiety, and difficulties performing usual activities for daily living. The TDF domains most relevant to the implementation of the LC pathway were beliefs about capabilities, environmental context and resources, knowledge, and reinforcement.

DISCUSSION: Our study provides novel insight into the development of a reactive multidisciplinary care pathway. Key drivers for successful implementation of LC services were identified, such as leadership, multidisciplinary teamwork, transferable skills, and knowledge exchange. Barriers to rapid set up of the service included funding constraints and the rapid evolution of an emergency context.

RevDate: 2026-06-26

Choi Y, Jacobs DR, Kramer HJ, et al (2026)

Associations of Pre-Pandemic CKD With Acute and Post-Acute COVID-19: The C4R Study.

American journal of kidney diseases : the official journal of the National Kidney Foundation pii:S0272-6386(26)00977-7 [Epub ahead of print].

RATIONALE & OBJECTIVE: While kidney failure is associated with severe COVID-19, data on early-stage chronic kidney disease (CKD) and its relationship to acute and post-acute COVID-19, as well as post-vaccination antibody responses, are limited. We evaluated pre-pandemic CKD stage in relation to these outcomes.

STUDY DESIGN: Prospective cohort.

SETTING & PARTICIPANTS: Adults in nine US population-based studies established since 1971, with pre-pandemic CKD measurements and follow-up for COVID-19 outcomes.

EXPOSURE: CKD stages (low CKD stage [reference], moderate CKD stage, high CKD stage, and very high CKD stage) defined by creatinine-based eGFR and urinary albumin-to-creatinine ratio.

OUTCOMES: (i) COVID-19 hospitalization or death (self-report/medical records, 2020‒2023); (ii) RECOVER Long COVID Research Index score ≥11 (LCRI-positivity by questionnaires, 2023‒2024); (iii) post-vaccination anti-Spike 1 (S1) IgG levels (dried blood spots, 2021‒2022).

ANALYTICAL APPROACH: Cause-specific hazards for severe COVID-19, logistic regression for LCRI-positivity, and generalized additive models for anti-S1 IgG.

RESULTS: Among 26,039 participants, CKD stage was low in 81.7%, moderate in 13.0%, high in 3.6%, and very high in 1.7%. Over a median 550-day follow-up (P25-P75: 314‒636), 734 had severe COVID-19; 12.1% of infected (669/5,527) were classified as LCRI-positive; and 3.1% (82/2,679) were anti-S1 IgG antibody non-reactive. A more severe CKD stage was associated with a greater risk for severe COVID-19: the HR for moderate stage CKD was 1.27 (95% CI, 1.03‒1.56), for high stage CKD, 2.33 (1.77‒3.06), and for very high stage CKD, 2.72 (1.88‒3.92). Higher CKD stages were associated with lower anti-S1 IgG levels: ‒12.00% (95% CI: ‒21.14% to ‒1.78%) for moderate stage CKD, ‒27.03% (95% CI, ‒40.00% to ‒11.25%) for high stage CKD, and ‒48.9% (95% CI, ‒61.60% to ‒32.01%) for very high stage CKD. A higher prevalence of LCRI positivity was observed only among infected individuals with very high stage CKD (OR=2.20; 95% CI: 1.16‒4.18).

LIMITATIONS: Some outcomes were self-reported.

CONCLUSION: Higher CKD stages were associated with a greater risk for severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed between CKD stage and LCRI-positivity except in individuals with very high stage CKD.

INDEX WORDS: Chronic kidney disease, kidney dysfunction, SARS-CoV-2 infection, severe COVID-19, Long COVID, anti-S1 IgG antibody, Prospective cohort.

RevDate: 2026-06-25

Kalansooriya W, Serra-Sastre V, M Jofre-Bonet (2026)

Non-communicable diseases, COVID-19 and labour market outcomes.

The European journal of health economics : HEPAC : health economics in prevention and care [Epub ahead of print].

The COVID-19 pandemic affected people with Non-Communicable Diseases (NCDs) in multiple ways. However, limited attention has been paid to its impact on labour outcomes for individuals with pre-existing NCDs. Given the heightened vulnerability of individuals with NCDs to COVID-19, the pandemic and related lockdown measures may have disproportionately influenced their employment prospects. Our study investigates the effects of the COVID-19 pandemic on the employment status and work hours of individuals with NCDs. We use data from the Understanding Society COVID-19 study in the UK, supplemented with main-stage Understanding Society surveys. We apply a difference-in-difference approach to estimate the pandemic’s impact on labour market outcomes over time. Our results indicate that COVID-19 significantly reduced both the likelihood of employment and working hours among individuals with NCDs relative to those without. These effects varied by age, gender, sector of employment (key workers vs. non-key workers), and type of NCDs. We further examine potential causes for the reduction in employment and working hours, and find that while the pandemic did not exacerbate existing health conditions among people with NCDs, their reduced labour market participation was largely driven by increased vulnerability to infection, the impact of long COVID, and the effects of public health interventions. Our study provides deeper insights into the post-pandemic contraction of the UK labour market, suggesting that the combined effects of NCDs and COVID-19 have contributed to a decline in workforce participation.

RevDate: 2026-06-25

Lin CJ, Bosco AA, Alves LI, et al (2026)

Post-COVID-19 diabetes outcomes.

Scientific reports pii:10.1038/s41598-026-42284-7 [Epub ahead of print].

Long-COVID-19 presentation has not been evaluated with proper depth in patients with diabetes (DM). This retrospective study evaluated 870 patients (320 DM, 550 non-DM) followed for up to 7.1 months post-hospitalization. Acute myocardial infarction, angina, articular edema, diarrhea, myocarditis/pericarditis were more frequent in patients with DM during the follow-up (p < 0.05). Recovery from COVID-19 symptoms was negatively associated with (89.8 × 94.27%; p = 0.038) while diarrhea, articular edema, abdominal pain, cardiovascular complications and worse health status were positively associated with DM. Patients with DM also had more frequent falls (21.1% × 11.1%; p = 0.0002033) and an increase in frailty scale score after COVID-19 (median of difference: 1 × 0; p = 6.124 × 10− 06). The quality of life of patients with diabetes was poorer with more frequent impaired mobility, inability to perform daily activity, discomfort and performed worse in physical and cognitive domains by WHODAS. Forty cases (7.3% of patients) of apparent new-onset diabetes were observed. Diabetes status did not affect the frequency of pain, skin problems, infections, newly diagnosed hypertension, abnormal lung sounds, post-COVID-19 hospital visit, anxiety and depression. Our data suggests a poorer outcome in diabetic patients and a 7.3% risk of diabetes progression in non-diabetic individuals up to 7.1 months after acute COVID-19.

RevDate: 2026-06-24

Virrantaus HR, Sirén M, Varonen M, et al (2026)

The course and trajectories of quality of life among post-COVID-19 patients in the HUS long covid cohort study.

Scientific reports pii:10.1038/s41598-026-59199-y [Epub ahead of print].

Patients with post-COVID condition (PCC) frequently report reduced quality of life (QoL). This study assessed QoL and health-related QoL (HRQoL) with trajectories within a prospective PCC cohort. The study included adult patients at a PCC clinic. Outcomes were collected at 0, 3, 6, and 12 months. The primary outcome was QoL by Visual Analogue Scale (VAS 0-10). Secondary outcomes included QoL by EUROHIS-QOL-8 and HRQoL by 15D, and patients' symptom perceptions by Somatic Symptom Disorder - B Criteria Scale (SSD-12). Linear mixed models analyzed temporal changes, and trajectory analysis modeled recovery patterns. At baseline, 442 patients participated, with 305 (69.0%) providing follow-up data. Most patients (92.7%) were non-hospitalized. Trajectory analysis of EUROHIS-QOL-8 identified two recovering trajectories (73.8%) and a stable group (26.2%). Stable trajectories were associated with more comorbidities and higher levels of worry-inducing symptom perceptions (mean SSD-12 score 26 out of 48), whereas marked recovery was linked to being employed and having lower SSD-12 (10-13). Mean QoL improved over 12 months from 5.2 to 6.5 on the 0-10 VAS scale and from 3.1 to 3.5 on the EUROHIS-QOL-8 scale of 1-5. HRQoL by 15D increased from 0.76 to 0.80 (scale 0-1). In conclusion, patients with comorbidities and distressing illness beliefs are the most vulnerable group in rehabilitation and require specific attention.

RevDate: 2026-06-24

Camargo SM, Dos Santos ALG, Maximo ST, et al (2026)

Assessing autonomic nervous system imbalance in long COVID-19 patients through heart rate variability during tilt testing.

Scientific reports pii:10.1038/s41598-026-38800-4 [Epub ahead of print].

Long COVID-19 is recognized as a condition associated with autonomic nervous system (ANS) dysfunction. However, quantitative evidence of its impact on heart rate variability (HRV) and blood pressure (BP) regulation during postural changes remains limited. This study assessed autonomic imbalance in post-COVID-19 patients by evaluating HRV and BP responses during tilt table testing, comparing long COVID-19 patients with healthy controls. A total of 61 participants were enrolled, 39 long COVID-19 patients (Study Group, SG) and 22 healthy controls (Control Group, CG). HRV was analyzed using time- and frequency-domain parameters. BP monitoring evaluated systolic, and diastolic blood pressure (SBP, and DBP respectively), and Pulse pressure (PP = SBP-DBP) was calculated for each phase. SG participants exhibited marked autonomic dysfunction during tilt. In the upright phase, they showed a significant increase in mean RR intervals (p = 0.0136), reduced normalized low-frequency (LF[†]) with p = 0.0316, increased normalized high-frequency (HF[†]) with p = 0.0315, and a decreased low-frequency/high-frequency (LF/HF) ratio (p = 0.0316), indicating a blunted sympathetic response and impaired autonomic adaptation to orthostatic stress. BP responses were also impaired: SG demonstrated attenuated changes in PP (ΔPP) when transitioning from the upright position to the recovery phase (p < 0.037). Within-group analysis confirmed persistent RR interval instability (p < 0.0001), incomplete normalization of LF and HF components (both p < 0.0001), and delayed recovery of PP after return to supine position. BP responses were also diminished: SG showed smaller ΔPP when moving from standing upright to the recovery phase (p < 0.037). Baroreflex sensitivity values did not differ between groups. Long COVID-19 patients display significant autonomic dysregulation, characterized by reduced HRV, abnormal BP responses. These findings highlight the value of tilt testing in uncovering hidden dysautonomia and support the need for targeted interventions, including pharmacologic modulation and long-term HRV/BP monitoring, to improve cardiovascular stability in long COVID-19.

RevDate: 2026-06-25

Vergara XP, Gibb K, Garvey KM, et al (2026)

Post-Acute COVID Among California Workers' Compensation Claims Filed in 2020-2022.

Journal of occupational and environmental medicine pii:00043764-990000000-01228 [Epub ahead of print].

OBJECTIVES: To examine sociodemographic risk factors for post-acute COVID (PASC) among California workers' compensation (WC) claims in 2020-2022.

METHODS: We matched WC claims to SARS-CoV-2 test data, augmented with external sociodemographic data, and estimated odds ratios (OR) using logistic regression models.

RESULTS: PASC accounted for 7% of the 206,375 COVID and PASC cases. PASC cases were more commonly 30-49 years old, female, longer tenured, and in healthcare and protective service occupations compared to acute COVID. The highest PASC OR were among workers 50-69 years old, and workers of color, including non-Latino American Indian/Alaska Native, Black, Native Hawaiian/Pacific Island, and multiple races, and healthcare practitioners.

CONCLUSIONS: During the first three years of the COVID pandemic, PASC was common among workers with WC claims in CA and unevenly distributed, with observed disparities by age, race, and occupation.

RevDate: 2026-06-25

Lerma-Irureta D, Presa-Gutiérrez E, Méndez-López F, et al (2026)

Biopsychosocial factors associated with health-related quality of life in long COVID: a matched case-control study in primary care.

BMC primary care pii:10.1186/s12875-026-03445-9 [Epub ahead of print].

BACKGROUND: Long COVID is associated with persistent symptoms, functional impairment, and reduced health-related quality of life (HRQoL), but the factors most strongly associated with poorer HRQoL remain incompletely characterized. This study compared adults with long COVID and recovered controls and identified variables independently associated with worse HRQoL.

METHODS: We conducted a case-control analysis of the ARALONGCOV 2022 dataset including 170 adults with prior COVID-19: 85 with long COVID and 85 recovered controls without persistent symptoms. HRQoL was assessed with the 12-item Short Form Health Survey (SF-12) total score. Additional measures included depressive symptoms (Patient Health Questionnaire-9, PHQ-9), fatigue severity (Fatigue Severity Scale, FSS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophizing, post-COVID functional status (PCFS), physical activity, and distance completed during the six-minute walk test (6MWT-D). Between-group comparisons used Mann-Whitney U tests for continuous variables and chi-squared or Fisher exact tests for categorical variables. Univariable and multivariable linear regression models were fitted within long COVID cases to identify factors independently associated with SF-12 total score.

RESULTS: Compared with recovered controls, participants with long COVID had markedly worse HRQoL (median SF-12 28.75 [IQR 21.25-39.17] vs 73.96 [62.81-77.50]; p < 0.001), more depressive symptoms (PHQ-9: 12.00 [7.00-18.00] vs 2.00 [0.00-6.00]; p < 0.001), greater fatigue (FSS: 57.00 [50.00-62.00] vs 13.00 [9.00-33.00]; p < 0.001), worse sleep quality (PSQI: 14.00 [9.00-16.00] vs 6.00 [3.00-11.00]; p < 0.001), and shorter 6MWT-D (481 [406-560] m vs 556 [491-609] m; p < 0.001). Long COVID cases were also less frequently employed (38.8% vs 81.2%; p < 0.001) and had more post-COVID comorbidity (88.2% vs 60.0%; p < 0.001). In the multivariable model within long COVID cases (n = 85), active employment was independently associated with better HRQoL (B 5.315, 95% CI 0.610 to 10.021; p = 0.027), whereas depressive symptoms (B - 1.124, 95% CI - 1.500 to - 0.748; p < 0.001) and post-COVID comorbidity count (B - 1.252, 95% CI - 2.484 to - 0.021; p = 0.046) were independently associated with worse HRQoL. Fatigue severity showed a borderline association in the same direction (B - 0.171, 95% CI - 0.343 to + 0.001; p = 0.051). The model explained 48.9% of the variance in SF-12 score within long COVID cases (R[2] = 0.489; adjusted R[2] = 0.463). Exploratory clustering did not identify discrete phenotypes; the burden distribution was more consistent with a continuous severity gradient. For descriptive purposes, a lower-burden stratum (33/78, 42.3%) and a higher-burden stratum (45/78, 57.7%) were operationalized and differed across symptom load, fatigue, mood, functional status, exercise capacity, and HRQoL.

CONCLUSIONS: Long COVID was associated with profound impairment in HRQoL compared with recovered controls. Depressive symptoms, post-COVID comorbidity burden, and lower active employment were the strongest independent correlates of poorer HRQoL; fatigue severity showed a borderline association in the same direction. These findings support multidisciplinary long COVID care models that integrate symptom control, mental health assessment, and social and occupational reintegration. Routine assessment of fatigue, depressive symptoms, post-COVID multimorbidity, and occupational status may help identify long COVID patients with the most severe concurrent HRQoL impairment, though longitudinal confirmation is needed to establish predictive utility.

TRIAL REGISTRATION: Trial registration: ISRCTN registry, identifier ISRCTN27312680.

RevDate: 2026-06-25
CmpDate: 2026-06-25

Senjam SS, Bansal G, Manna S, et al (2026)

Self-reported Long COVID and its Determinants in a Rural North Indian Adult Population: Lessons Learnt from the Pandemic.

Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine, 51(3):490-496.

BACKGROUND: Most studies on long COVID-19 symptoms (LCSs) are conducted in urban areas or hospital. To date, relevant evidence in LCS from community-based rural studies is lacking. Therefore, the present study aimed to investigate LCS and its determinants in a rural adult population of northern India.

METHODS: A cross-sectional study was conducted in a rural district, Jhajjar, Haryana in 2023. Forty clusters were covered from one randomly selected subdistrict. A semistructured questionnaire on the SurveyMonkey platform consisted of questions related to sociodemographic profile, health problems, pre-existing morbidity, LCS, and functional difficulties. The data regarding infection with COVID-19 were collected based on self-reported positive testing for SARS-CoV-2 on RT-PCR.

RESULTS: Out of the 3700 enumerated, 2954 (79.8%) were surveyed. The self-reported infection rate was 6.2% (183/2954, 95% CI: 5.3-7.1). Further, 23% (42/183, 95% CI: 17.01-29.7) of infected cases have LCS, whereas 1.4% (42/2954) of the study population have LCS. The prevalence of LCS was higher in females than in males (28.7% vs 17.7%). Weakness (14, 33.4%), weight loss (6,14.3%), memory problems (6, 14.3%), and headache (4, 9.5%) were common reported LCSs. Univariable analysis revealed a significantly lower risk of LCS in the age group of 26-35 years (OR 0.32, 95% CI: 0.10-0.83, P = 0.019). In contrast, higher risk was observed with lower education (OR 4.46, 95% CI: 1.47-13.78, P = 0.003), and pre-existing morbidities such as seeing difficulty (OR 2.91, 95% CI: 1.09-7.58, P = 0.021, difficulty in self-care (OR 3.72, 95% CI: 1.07-12.88, P = 0.021), and communication difficulties (OR 5.28, 95% CI: (0.76-45.74, P = 0.046).

CONCLUSION: A higher probability of LCS is found among females of older age, participants with lesser education, and pre-existing comorbidities.

RevDate: 2026-06-25
CmpDate: 2026-06-25

Ren Z, Liu X, Sun W, et al (2026)

Recombinant RBD-based subunit vaccines incorporating high-frequency mutation sites elicit cross-immunity and robust protection against SARS-CoV-2.

Frontiers in microbiology, 17:1806270.

INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), a highly pathogenic coronavirus (CoV) belonging to Coronavirus B, has triggered outbreaks or pandemics. Currently, many variants of SARS-CoV-2 have evolved, which exhibit severe immune evasion and imprinting resistance to existing vaccines and cause infected individuals to develop Post-Acute Sequelae of SARS-CoV-2 (also termed Long-COVID). This underscores the public health importance of developing effective vaccines with broad-spectrum efficacy against the SARS-CoV-2 variant and other CoVs with pandemic potential.

RESULTS: In this study, we expressed three tandem-repeat dimeric recombinant RBD proteins using an insect-baculovirus expression system integrated with the high-frequency SARS-CoV-2 RBD mutation sites. We performed immunogenicity assessment and attack protection tests. The date showed that these innovative SARS-CoV-2 RBD recombinant protein vaccines could show varying degrees of cross-immunity response and potent protection against SARS-CoV-2.

CONCLUSION: Overall, our results indicated that these recombinant RBD subunit vaccines could serves a promising platform for a universal vaccine against SARS-CoV-2 and its variants, and provide a new perspective for the design of other future pandemic vaccines.

RevDate: 2026-06-25
CmpDate: 2026-06-25

Srikanth S, Ivankovic D, Gonzales L, et al (2026)

Cellular Metabolic Signatures of Long COVID-19.

Infectious disease reports, 18(3):.

BACKGROUND/OBJECTIVES: Long COVID-19 (LC-19), also known as Post-Acute COVID-19 Syndrome (PACS), is a chronic condition some people experience after an initial SARS-CoV-2 infection. The etiology of this complex, multifactorial disease remains largely unknown, although various theories have been propounded. This study aims to profile and compare the metabolic activity of cells of normal and LC-19 patients.

METHODS: A cohort of 20 individuals, 10 with LC-19 and 10 without LC-19, was selected based on their post-COVID-19 symptomatology. Saliva was tested for opportunistic viruses like Epstein-Barr virus (EBV) and Human Herpesvirus 6 (HHV-6). Lymphoblastoid cell lines derived from blood were analyzed using the Biolog Phenotype Mammalian Microarrays (PM-M1, PM-M6, and PM-M7) to assess metabolic activity across a wide array of growth substrates and effector molecules.

RESULTS: Unique metabolic profiles emerged across the controls and LC-19 groups. The SARS-CoV-2 infection causes an over two-fold enhanced utilization of glycolytic and anaerobic substrates and a reduced response to growth factors and effectors. The increased energy source utilization assessed in PM-M1 is unsustainable, and the LC-19 groups demonstrate this with a clear correlation with the number of LC-19 symptoms, demonstrating a trend consistent with metabolic reprogramming. The infection also results in a reduced response to growth factors and effectors, assessed in PM-M6 and PM-M7, with the level of reduction commensurate with the symptom burden.

CONCLUSIONS: The data from the patient groups were analyzed and compared to construct a metabolic profile unique to individuals who developed LC-19, which could, in the future, be used for diagnosis and to identify targets for therapeutic intervention. Our study identified an LC-19-specific metabolic profile indicative of adaptive responses to stress, cellular dysfunction, and prolonged inflammation, leading to the reprogramming of bioenergetic pathways.

RevDate: 2026-06-25
CmpDate: 2026-06-25

Lică IMO, Țincu IF, Drăgănescu AC, et al (2026)

Factors Associated with Long COVID in the Pediatric Population: A Retrospective Case-Control Study.

Clinics and practice, 16(6):.

Background: Long COVID in children is increasingly recognized, yet its clinical predictors and objective biological correlates remain insufficiently characterized. Objectives: The objective was to compare clinical, demographic, and laboratory characteristics between children with and without long COVID and to identify associated variables. Methods: We conducted a retrospective observational case-control study at the "Dr. Victor Gomoiu" Children's Clinical Hospital, including pediatric patients with confirmed SARS-CoV-2 infection. Cases were defined as children with symptoms persisting ≥12 weeks after acute infection, while controls had no persistent symptoms at ≥12 weeks. Results: Eighty-nine children with long COVID and 88 matched controls were included. Children with long COVID were significantly older (1.79 ± 0.90 vs. 1.14 ± 0.80 years, p < 0.001) and more frequently from urban areas (86.5% vs. 69.3%, p = 0.0099). Lymphocyte, monocyte, and basophil counts were significantly lower in the Long COVID group, while D-dimer, ferritin, serum iron, urea, and creatinine levels were significantly higher. A multivariate predictive model demonstrated excellent discrimination (AUC = 0.94), with optimal sensitivity (84.3%) and specificity (89.8%) at a probability threshold of 0.48. Conclusions: Long COVID in children was associated with identifiable clinicobiological features. An exploratory composite model showed good discrimination but requires external validation.

RevDate: 2026-06-25

Lv F, Chen Y, Y Xia (2026)

Neurological sequelae of Long COVID: Pathophysiological mechanisms, diagnostic advances, and therapeutic perspectives.

Journal of neuroimmunology, 419:579010 pii:S0165-5728(26)00159-1 [Epub ahead of print].

SARS-CoV-2 infection may result in persistent neuropsychiatric symptoms beyond the acute phase, often discussed under the umbrella term "Long COVID". These manifestations commonly include mood disturbances, post-traumatic stress symptoms, cognitive impairment, sleep disturbances, and fatigue, with substantial effects on daily functioning and quality of life. Despite these concerns, the pathophysiological mechanisms underlying these sequelae remain poorly understood, and the lack of specific biomarkers hampers the development of targeted interventions. This review synthesizes recent advances in the clinical presentation, underlying mechanisms, diagnostic approaches, and therapeutic strategies for neuropsychiatric sequelae of Long COVID. We also discuss current challenges and outline future research priorities to facilitate the establishment of standardized diagnostic criteria and the development of effective, mechanism-based therapies.

RevDate: 2026-06-25

Nairn B, Walz ID, Nikitas C, et al (2026)

Investigating the feasibility and acceptability of the TeleRehabilitation of balance clinical and economic Decision Support System (TeleRehaB DSS) in adults at risk of falls: study protocol for a multicentre clinical trial.

BMJ open, 16(6):e108821 pii:bmjopen-2025-108821.

INTRODUCTION: Falls are a significant concern for older adults, particularly those with neurological, vestibular, cognitive and post-viral conditions, due to dizziness and imbalance. Conventional balance rehabilitation programmes, though effective, face challenges in adherence and accessibility. The TeleRehabilitation Decision Support System (TeleRehaB DSS) uses artificial intelligence (AI) and motion tracking to provide individualised multisensory balance rehabilitation (MBR) remotely. This trial aims to evaluate the acceptability, feasibility, safety and preliminary efficacy of a home-based TeleRehaB DSS among community-dwelling older adults at risk of falls due to stroke, mild cognitive impairment (MCI), long COVID and vestibular dysfunction.

METHODS AND ANALYSIS: This multicentre, assessor-blinded randomised controlled trial will recruit 460 community-dwelling adults aged 40-80 years with stroke, MCI, vestibular dysfunction or long covid across five sites in the UK, Europe and Southeast Asia. Participants will be randomised to a 9-week remotely supervised home exercise programme using either TeleRehaB DSS (high-tech or low-tech MBR with exergames and cognitive training) or standard care (OTAGO home exercise programme or Meniere's Dizziness booklet). Primary outcomes include feasibility, acceptability and safety, alongside clinical measures of balance and health-related quality of life (Functional Gait Assessment, EuroQol five-dimensional descriptive system instrument). Secondary outcomes assess balance, cognition, physical activity, dizziness, psychological well-being, fatigue and confidence. Usability, user experience and digital health literacy will also be evaluated. Anonymised data will undergo quality checks and be analysed using descriptive and exploratory statistics, mixed-effects models, cost-effectiveness analysis (incremental cost-effectiveness ratio) and thematic analysis of qualitative interviews, adjusting for site and relevant confounders.

ETHICS AND DISSEMINATION: This study has received institutional ethical approvals in the UK, Germany, Greece and Thailand and from Madeira, Portugal. Findings from this study will be submitted for peer-reviewed publications.

TRIAL REGISTRATION NUMBER: NCT06534164.

RevDate: 2026-06-25

Leão FC, Prazeres CLS, Godoy MDCL, et al (2026)

Functional and structural olfactory changes in post-COVID-19 patients detected by 7 Tesla MRI.

Scientific reports pii:10.1038/s41598-026-59851-7 [Epub ahead of print].

Persistent olfactory dysfunction after SARS-CoV-2 infection is common, yet its central neural profile remains poorly defined. We combined ultra-high-field 7 Tesla resting-state functional MRI with surface-based cortical morphometry to characterise olfactory-network organisation and cortical structure in long-term post-COVID dysosmia. Thirty adults (14 with persistent dysosmia; 16 normosmic controls) completed psychophysical olfactory testing and 7 Tesla imaging. Connectivity analyses across 56 olfaction-related regions revealed a coherent pattern centred on insular, orbitofrontal and thalamic nodes: connectivity was reduced between the insula and the orbitofrontal and entorhinal cortices, and between the ventral posterior thalamus and the ventral insula, and increased between interhemispheric orbitofrontal regions and among anterior thalamic nuclei. Significant connections were predominantly right-lateralised or interhemispheric. Morphometry showed no volumetric differences but selective left orbitofrontal thinning. Across the whole sample, greater orbitofrontal and insular thickness was associated with better olfactory performance; however, this reflected the difference between patients and controls rather than a graded relationship within the patient group, and did not persist after accounting for group and age. Together, these findings provide a preliminary, proof-of-concept characterisation of an orbitofronto-insular signature of long-term post-COVID dysosmia and nominate candidate imaging markers for testing in larger, multi-centre cohorts.

RevDate: 2026-06-23

Changela S, Katz R, Shah J, et al (2026)

Risk of new-onset obstructive sleep apnea up to 4.5 years after COVID-19 in the urban population.

Scientific reports pii:10.1038/s41598-026-56469-7 [Epub ahead of print].

Obstructive sleep apnea (OSA) is linked to cardiovascular, metabolic, and cognitive morbidity. Although COVID-19 has been associated with long-term respiratory and neurological sequelae, its role in precipitating new-onset OSA remains unclear. We evaluated whether SARS-CoV-2 infection increases risk of developing OSA up to 4.5 years post-infection and how risk varies by hospitalization status, demographics, comorbidities, and vaccination status. This retrospective cohort study used electronic health records from the Montefiore Health System in the Bronx. Adults tested for SARS-CoV-2 between March 1, 2020, and August 17, 2024, were classified as hospitalized COVID+ , non-hospitalized COVID+ , or COVID- . Patients with prior OSA or loss to follow-up were excluded. Inverse probability weighting adjusted for demographic, clinical, socioeconomic, and vaccination covariates. New-onset OSA was assessed using weighted Cox proportional hazards models. Secondary outcomes including hypertension, myocardial infarction, heart failure, stroke, arrhythmia, pulmonary hypertension, type 2 diabetes, and obesity of individuals who developed new-onset OSA were evaluated with Poisson regression. Sensitivity analysis used a pre-pandemic control cohort. Among 910,393 eligible patients, hospitalized [HR 1.41 (95% CI 1.14-1.73)] and non-hospitalized [HR 1.33 (95% CI 1.22-1.46)] COVID+ patients had higher adjusted risk of new-onset OSA versus COVID- controls. Similar findings were observed when compared to the historical controls (n = 621,046). After OSA onset, hospitalized COVID+ patients had higher risks of heart failure and pulmonary hypertension, while non-hospitalized COVID+ patients had higher risk of obesity vs COVID- patients. SARS-CoV-2 infection is independently associated with increased risk of new-onset OSA. These findings support targeted screening post-COVID in high-risk populations.

RevDate: 2026-06-24
CmpDate: 2026-06-24

Kunc P, Fabry J, Mazuchova J, et al (2026)

Serological Profiling and Neuro-Immune Resilience: The Dissociation Between Anti-SARS-CoV-2 Antibodies and Post-Viral Airway Hyperresponsiveness in Pediatric Asthma.

Lung, 204(1):.

BACKGROUND: Chronic cough is a frequent symptom of pediatric Long COVID, hypothetically driven by viral neurotropism and sensory nerve sensitization. We investigated the neuro-immune axis in pediatric asthma to determine if the magnitude of post-SARS-CoV-2 humoral immunity correlates with objective airway afferent nerve hypersensitivity.

METHODS: This prospective observational study included 61 pre-pubertal children (aged 8 to < 12 years) with well-controlled, predominantly inhaled corticosteroid (ICS)-treated (93.4%) bronchial asthma and confirmed past SARS-CoV-2 infection. Systemic humoral memory was quantified via anti-Spike IgG and IgA titers. Objective cough reflex sensitivity was measured using a capsaicin challenge test, establishing C2 and C5 values. Subjective symptom burden was evaluated using parent-proxy questionnaires (PCQ, VAS, PedsQL).

RESULTS: Stratification by median anti-Spike IgG (125.77 BAU/ml) revealed no significant differences in basal (C2, p = 0.301) or motor response (C5, p = 0.714) capsaicin thresholds between robust and waning humoral memory states. IgA stratification yielded identical results. Spearman's correlation confirmed a complete lack of association between absolute IgG titers and neurophysiological markers (p > 0.05). Crucially, parent-reported chronic cough severity (PCQ, VAS) and asthma-specific quality of life demonstrated a complete dissociation from objective capsaicin thresholds across all evaluated domains (all p > 0.05). Supplementary subgroup analysis revealed no significant differences in cough thresholds based on acute COVID-19 severity (p > 0.05).

CONCLUSION: A robust post-viral humoral immune response to SARS-CoV-2 does not precipitate peripheral airway nerve hypersensitivity in properly controlled, ICS-treated asthmatic children. The complete uncoupling of subjective parent-reported symptoms from objective neurophysiology cautions against diagnosing neurogenic Long COVID based solely on questionnaires, emphasizing the necessity of objective testing and evaluation of alternative atopic etiologies.

RevDate: 2026-06-24
CmpDate: 2026-06-24

Mosabbir A, Meltzer JA, Uryash A, et al (2025)

Cognitive rehabilitation among long COVID patients using vibratory and auditory treatment (VAT) is linked to BDNF.

Frontiers in cognition, 4:1692578.

Cognitive dysfunction occurs in around 40% of long COVID (LC) patients, and in many cases appears second only to fatigue in prevalence. Vibratory and auditory treatment (VAT) within the gamma range has demonstrated improvements in symptoms associated with cognition and fatigue. In this open-label pilot study, we tested the effects of VAT on measures of cognition and fatigue in LC. Twenty patients were randomly divided into a treatment and a control group. Symptoms were monitored remotely through mobile apps and in-person visits before and after the treatment period. The treatment group received a device generating 40 Hz of VAT to take home and use every day from Monday to Friday for 4 weeks (i.e., 20 sessions over 28 days), whereas the control group did not use any device but followed the same data collection procedures. This study found that after 4 weeks of VAT, participants with LC exhibited increased performance in selective attention and response inhibition, an increased amount of circulating brain-derived neurotrophic factor (BDNF), and a reduced resting heart rate. We propose that VAT may be a useful rehabilitative tool for LC as well as other targeted populations that seek improvements in cognition or general health but are compromised immunologically or physically.

RevDate: 2026-06-24
CmpDate: 2026-06-24

Green TD, McWilliams C, de Figueiredo L, et al (2026)

Algorithm dependence of patient phenotypes in Long COVID: a patient-led, multi-method clustering of 6031 patients using 162 self-reported symptoms.

Oxford open immunology, 7(1):iqag010.

OBJECTIVES: Long COVID, characterized by symptoms that remain or emerge in the months after acute COVID-19 infection, is a multisystemic condition with highly variable patient presentations. Phenotyping studies have reported divergent symptom clusters, increasingly used to design trials and interpret biomarker data. However, robustness of these clusters across analytic methods remains uncertain.

METHODS: We analyzed data from 6 031 adults with ≥ 90 days of illness from a patient-led international survey. Participants reported presence/absence of 162 symptoms, post-exertional malaise severity and demographics. We applied three unsupervised machine learning approaches to the same symptom matrix, evaluating the resulting clusterings for concordance, robustness to subsampling, and relationship to symptom burden, post-exertional malaise severity, age and gender.

RESULTS: Each method produced clinically plausible symptom clusters, but concordance across methods was low. All three approaches identified a high-symptom-burden group enriched for post-exertional malaise severity, and lower-symptom-burden groups with older mean age and a lower proportion of women. Symptom count consistently correlated with higher post-exertional malaise severity and a greater proportion of women. Manifold analysis revealed that the overall symptom space was largely continuous, lacking clear cluster boundaries.

CONCLUSIONS: The strong dependence of patient clusters on algorithm choice suggests that single-method Long COVID phenotyping may produce incomplete or unstable subgroup definitions. Clustering methods may impose artificial boundaries on a smoothly varying symptom landscape, especially in studies capturing fewer symptoms. Phenotyping efforts should assess clustering robustness and avoid overinterpreting single-method results. Our multi-method analysis highlights the importance of considering the full breadth of patient symptoms when evaluating treatments.

RevDate: 2026-06-24
CmpDate: 2026-06-24

Theodoro EL, Prediger KM, Damacena MA, et al (2026)

Oral manifestations associated with long COVID: a scoping review.

Revista brasileira de enfermagem, 79:e20250198 pii:S0034-71672026000101010.

OBJECTIVES: to map scientific evidence on oral manifestations originating during long COVID.

METHODS: this is a scoping review based on the method described by JBI. Primary articles published in Portuguese, English, and Spanish between March 2020 and December 2024 were included from the PubMed, Web of Science, Virtual Health Library, Scopus, Excerpta Medica dataBASE, and Scientific Electronic Library Online databases, and a descriptive analysis was performed.

RESULTS: of the 15 studies analyzed, the most frequent oral manifestations of long COVID were taste alterations, xerostomia, difficulty chewing, gingival bleeding, periodontitis, and changes in the teeth.

CONCLUSIONS: an association between long COVID and various oral manifestations was evidenced, impacting the quality of life of patients. Factors such as age, comorbidities, and social inequalities influence the persistence of these manifestations, with a higher prevalence in women. Multiprofessional collaboration and clearer guidelines are essential to improve dental care.

RevDate: 2026-06-24

Epsi NJ, Richard SA, Morris MJ, et al (2026)

Is cellular senescence a biological feature of Long COVID? A transcriptomic analysis across comparative post-acute sequelae phenotypes.

The Journal of infectious diseases pii:8713052 [Epub ahead of print].

INTRODUCTION: Cellular senescence, involving cell-cycle arrest and inflammatory factor release, may play a role in Long COVID development. We investigated the role of senescence-associated genes across multiple post-acute sequelae phenotypes.

MATERIALS AND METHODS: Participants from a cohort study were grouped into post-COVID-19 groups: (i) sensory, fatigue/difficulty thinking, and difficulty breathing/exercise intolerance, identified through a machine learning (ML) analysis of symptom data; (ii) cognitive impairment, measured using a screening cognitive assessment tool (BRACE); and (iii) persistent dyspnea, identified using a symptom-scale known to correlate with a six-minute-walk-test. Post-infection whole blood samples underwent transcriptomic analysis with 47,125 genes used as the reference signature for gene set enrichment analysis (GSEA) against the SenMayo cellular-senescence query gene set (n = 125); enrichment were based on normalized enrichment scores (NES).

RESULTS: SenMayo genes were significantly upregulated in the early post-infection period in (a) 56 individuals who subsequently developed Long COVID symptom phenotypes, compared to 104 who did not develop Long COVID symptoms (NES = 6.04, P = 0.001); (b) 32 individuals with long-term cognitive impairment compared to 40 without long-term cognitive impairment measured by BRACE (NES = 2.58, P = 0.032); and (c) 26 participants who had persistent dyspnea compared to 53 without persistent dyspnea measured by the validated dyspnea instrument (NES = 6.29, P = 0.001). ETS2 was upregulated across all impairment-related phenotypes, while other SenMayo genes showed phenotype-specific variability.

CONCLUSIONS: This study suggests a role of senescence-associated genes in the development of Long COVID, including shared and unique transcriptomic patterns across phenotypes.

RevDate: 2026-06-24
CmpDate: 2026-06-24

Dasarathy D, Luk JW, Shui AM, et al (2026)

Evaluating acute and post-acute COVID-19 symptoms among patients with and without alcohol-related cirrhosis: implications for quality management.

Alcohol and alcoholism (Oxford, Oxfordshire), 61(4):.

BACKGROUND: Patient-reported symptoms following COVID-19 exposure have been understudied in cirrhosis. This study evaluated type, severity, and persistence of symptoms along with impact on quality of life (QOL) post-SARS-CoV-2 infection in a cohort with and without alcohol-related cirrhosis.

METHODS: Patients with cirrhosis receiving care in hepatology clinics at three institutions were surveyed for symptoms and liver disease QOL (LDQOL) using standardized instruments following SARS-CoV-2 infection. Acute (<30 days), post-acute (≥30 days since onset), and Long COVID (≥3 months) symptoms were compared by cirrhosis etiology and decompensated status. Associations between severe COVID-19 symptoms and LDQOL were examined using multivariable models.

RESULTS: 156 patients with prior COVID-19 exposure had a median age of 66.5 years; 18% were female; 43% had alcohol-related liver disease (ALD); and 42% decompensated cirrhosis. Among 208 surveys conducted, the median (Q1, Q3) number of symptoms reported was 6 (3, 10), with 66% reporting at least one severe/very severe symptom and 21% had Long COVID. There were no significant differences in symptoms by cirrhosis etiology or decompensation except those with ALD had higher post-acute symptoms compared to non-ALD (RR 2.17, P = .04). Moreover, the total number of severe symptoms was inversely associated with LDQOL. For each additional severe symptom reported, LDQOL decreased by 1.12 points after adjusting for age, sex, ALD, decompensated cirrhosis, and MELD-Na score (95% CI -1.70 to -0.53, P = .001).

CONCLUSIONS: Assessing severity and persistence of post-COVID-19 exposure symptoms can help clinicians address patient-reported QOL concerns, optimize cirrhosis management, and inform integrated care for ALD and AUD.

RevDate: 2026-06-24

Giunta S, Sabbatinelli J, Olivieri F, et al (2026)

Aging-related autonomic nervous system imbalance and adrenergic regulation of immunity: Implications for inflammaging, autoimmunity, and long COVID.

Frontiers in neuroendocrinology pii:S0091-3022(26)00039-7 [Epub ahead of print].

The autonomic nervous system (ANS) plays a central role in immune homeostasis by integrating sympathetic and parasympathetic signals that regulate inflammation, immune cell trafficking, and tolerance. Aging is associated with a progressive autonomic imbalance characterized by sympathetic overactivation, reduced parasympathetic tone, and impaired β-adrenergic signaling in immune cells, which together contribute to inflammaging and immune dysregulation. In this review, we discuss how aging-related alterations in adrenergic pathways affect immune cell differentiation and cytokine networks, with particular emphasis on β2-adrenergic control of the Th17/regulatory T cell balance through cAMP-dependent mechanisms interacting with cytokine-driven STAT signaling. Chronic sympathetic stimulation and β-adrenergic desensitization weaken these regulatory constraints, favoring pro-inflammatory immune trajectories and loss of immune tolerance. Finally, we propose Long COVID as a paradigmatic condition in which pre-existing inflammaging and autonomic vulnerability are amplified by viral infection, leading to persistent inflammation, impaired immune regulation, and increased susceptibility to autoimmune manifestations.

RevDate: 2026-06-24

Dennis C, NA Alwan (2026)

What does it mean to recover from long covid?.

BMJ (Clinical research ed.), 393:e100054.

RevDate: 2026-06-24

Mulet A, Signes-Costa J, Fernández-Fabrellas E, et al (2026)

Mitochondrial Dysfunction and Telomeric Shortening as Long-term Complications After COVID-19.

Archivos de bronconeumologia pii:S0300-2896(26)00159-6 [Epub ahead of print].

OBJECTIVES: To evaluate the potential role of telomere shortening and mitochondrial dysfunction in the development of long-term complications of COVID-19, including pulmonary fibrosis.

METHODS: We analyzed 132 patients from the prospective COVID-FIBROTIC cohort 1 year after hospitalization for bilateral pneumonia. Leukocyte telomere length was measured and compared with that of 78 age- and sex-matched controls. Fibrosis biomarkers and radiological findings were assessed at 2 and 12 months. In a subgroup of 44 patients, mitochondrial protein expression was evaluated 2 years after infection using reverse-phase protein arrays. Associations among telomere length, mitochondrial proteins, inflammatory markers, and fibrotic sequelae were analyzed.

RESULTS: Leukocyte telomere length was significantly shorter in patients than in controls (AUC, 0.84; P<.0001), independent of age or acute disease severity. At 12 months, 29% of patients showed fibrotic lung changes on HRCT. Elevated periostin and IL-6 levels correlated with persistent mitochondrial protein alterations at 2 years. Mitochondrial proteins such as ETFβ and PKM2 differentiated patients with fibrotic sequelae and those with marked telomere attrition, suggesting their role as biomarkers. Moreover, in patients with fibrosis, telomere shortening correlated inversely with ACO1 levels, a protein involved in oxidative stress and iron metabolism.

CONCLUSIONS: SARS-CoV-2 infection induces sustained telomere shortening and long-term mitochondrial dysfunction, both of which are associated with fibrotic sequelae. These findings support a pathogenic link among mitochondrial dysregulation, telomere attrition, and pulmonary fibrosis, resembling mechanisms described in idiopathic pulmonary fibrosis. Monitoring these biomarkers may help identify patients at risk of chronic post-COVID complications.

RevDate: 2026-06-22

Guedj E, Verger A, T Horowitz (2026)

Brain [18F]FDG PET in Subjective Cognitive Complaints: From Diagnostic Gap to Neurobiological Insight.

PET clinics pii:S1556-8598(26)00049-0 [Epub ahead of print].

Subjective cognitive complaints are heterogeneous and may occur with normal, subtle, or objectively abnormal cognitive testing. Fluorodeoxyglucose (FDG) PET can help explore their metabolic substrate, particularly in subjective cognitive decline within the Alzheimer's disease continuum. In mild traumatic brain injury and long coronavirus disease (COVID), available studies suggest possible metabolic-network abnormalities but involve more heterogeneous populations and should be interpreted cautiously within multimodal, clinically characterized frameworks.

RevDate: 2026-06-22

Akbar N, Phadke S, Mehelay S, et al (2026)

Symptoms, Functional Impact and Perceived Healthcare Barriers Experienced by Racialized Communities Living with Long COVID in Canada: A Mixed-methods Study.

Journal of racial and ethnic health disparities [Epub ahead of print].

BACKGROUND: Post COVID-19 Condition (PCC) or Long COVID has been shown to be more prevalent among racialized communities. The symptoms and lived experiences of racialized communities living with Long COVID in Canada has yet to be reported.

OBJECTIVE: To describe the symptoms, functional impact, and perceived barriers and facilitators to treatment and/or rehabilitation for racialized communities living with Long COVID in Canada. To further explore whether there are differences across racial groups (including comparison to non-racialized/ White) with regards to symptoms, functional impact, and perceived healthcare barriers.

METHODS: Convergent parallel mixed-methods design, which included quantitative measures and qualitative semi-structured interviews with 49 participants, with a large proportion (59%) of participants self-identifying as racialized (predominantly Black and South Asian).

RESULTS: The rates of severe fatigue and clinically significant depression for the entire sample were high at 88% and 78% respectively. Long COVID had major negative functional impacts, with 27% of participants not being able to return to full-time work since contracting COVID-19. The biggest barrier to treatment and rehabilitation was dismissal by healthcare providers, which was exacerbated by factors including gender identity (being a woman) and race. Black participants reported more discrimination compared to White participants, which correlated with more severe depression.

CONCLUSIONS: Less dismissal of symptoms by healthcare providers and greater mental health support are needed, especially for racialized communities living with Long COVID. There is also a need for more employer and government financial support and for healthcare organizations to address discrimination and anti-Black racism in healthcare.

RevDate: 2026-06-23
CmpDate: 2026-06-23

Chikkala RKP, Garre S, Pratyusha AC, et al (2026)

Exploring Coagulation Abnormalities and Functional Impairment in Long COVID: Relevance to Primary Care Practice.

Cureus, 18(5):e109403.

Background The long-term sequelae of COVID-19, collectively termed long COVID, manifest as persistent symptoms that may be driven by ongoing coagulation abnormalities. Early identification, particularly in primary care, requires simple, low-cost tools that do not rely on advanced diagnostics. This study evaluated the usefulness of basic coagulation markers and the Six-Minute Walk Test (6MWT) in assessing symptom severity and functional limitation among individuals with long COVID. Methodology A two-phase observational study was conducted from July 2022 to January 2024. Phase I enrolled 197 adults more than six weeks post-COVID-19 who presented with fatigue, breathlessness, reduced exercise tolerance, cough, or musculoskeletal pain. Baseline investigations included C-reactive protein (CRP), prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, and platelet count, alongside the 6MWT. The primary objective was to evaluate the association between coagulation abnormalities and the severity of long COVID symptoms. Secondary objectives included assessment of functional impairment using the 6MWT and evaluation of persistence of coagulation abnormalities at the three-month follow-up. Patients with abnormal baseline coagulation or inflammatory parameters (n = 63) underwent repeat evaluation after three months. Results The study included 197 participants with a mean age of 37.3 ± 11.97 years, of whom 87 (44.2%) were male. Reduced effort tolerance was the most common presenting symptom, observed in 151 (76.7%) patients. At baseline, abnormalities were noted in D-dimer (50 (25.4%)), fibrinogen (43 (21.8%)), CRP (34 (17.3%)), aPTT (23 (11.7%)), PT/INR (21 (10.7%)), and platelet count (10 (5.1%)). Patients with severe symptoms demonstrated significantly higher levels of D-dimer and fibrinogen (p < 0.001 for both). Elevated D-dimer (50 (25.4%)) and fibrinogen (43 (21.8%)) were associated with an increased risk of severe symptomatology, with relative risks of 3.0 and 2.34, respectively. At the three-month follow-up, persistent elevation of D-dimer (32 (50.8%)) and fibrinogen (30 (47.6%)) was observed, indicating sustained coagulation abnormalities in a substantial subset of individuals with long COVID. Conclusions This study demonstrates a significant association between elevated D-dimer and fibrinogen levels and symptom severity in patients with long COVID. Simple, accessible tools, particularly basic coagulation tests and the 6MWT, may serve as useful adjunctive assessments for primary care physicians to identify long COVID patients with probable ongoing thrombo-inflammatory activity. Integrating these assessments into routine follow-up may improve early detection, monitoring, and targeted referral.

RevDate: 2026-06-23

Habib K, Sethi SM, Khanum I, et al (2026)

Knowledge, Attitudes, and Practices of Physicians in Pakistan Toward COVID-19 and Long COVID: A Cross-Sectional Survey.

Asia-Pacific journal of public health [Epub ahead of print].

Long COVID has emerged as an important post-pandemic health challenge, yet physician awareness in low- and middle-income countries remains limited. This multicenter cross-sectional study assessed the knowledge, attitudes, and practices of physicians in Pakistan regarding COVID-19 and Long COVID using an online survey conducted in 2024. A total of 117 physicians participated. While knowledge of acute COVID-19 was generally adequate, with 74.4% achieving good scores, knowledge of Long COVID was considerably lower, with only 30.8% demonstrating adequate understanding. Although most participants recognized common Long COVID symptoms (94.9%), fewer correctly identified its formal definition (37.6%). Attitudes toward COVID-19 prevention and management were largely positive (86.3%), and most participants reported appropriate clinical practices (97.4%). Female physicians had higher odds of adequate Long COVID knowledge, whereas those with more than 10 years of experience had significantly lower knowledge levels. These findings highlight a substantial gap in physician awareness of Long COVID despite strong preparedness for acute COVID-19. Targeted educational interventions are needed to improve recognition and management of post-COVID conditions, particularly in resource-limited settings.

RevDate: 2026-06-23

van Bilsen CJA, Wijnen SMCE, Pagen DME, et al (2026)

Workforce exit and work productivity loss in adults with and without post-COVID-19 condition: the PRIME post-COVID cohort study.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases pii:S1201-9712(26)00548-5 [Epub ahead of print].

BACKGROUND: Post-COVID-19 condition (PCC) is highly prevalent, yet evidence on its long-term impact on work participation remains limited. This study assessed workforce exit and work productivity loss among adults with PCC compared to those recovered or without PCC.

METHODS: In this prospective cohort study (PRIME post-COVID) in the Netherlands, we used online questionnaire data from adults with a positive COVID-19 test between June 2020 and September 2022. Participants were categorized as PCC (not feeling recovered ≥3 months post-infection), Recovered, or Never PCC. All were employed in 2022, and workforce exit, work productivity loss, work incapacity, and financial strain were evaluated in 2024.

FINDINGS: The two-year workforce exit rate was 17% in PCC (N=790), 10% in Recovered (N=437), and 9% in Never PCC (N=2,115). Rates were higher among those with PCC, older age, and health conditions. Absenteeism and presenteeism were up to three times higher in PCC and two times higher in Recovered, compared to Never PCC. Among non-employed participants, work incapacity was highest in PCC (46%) versus Recovered (17%) and Never PCC (12%). Financial strain was highest in non-employed PCC (54%) and lowest in employed Never PCC (19%).

CONCLUSION: PCC substantially impacts workforce participation and productivity. Support, interventions, and awareness are urgently needed.

RevDate: 2026-06-23

Yang Y, Kanerva M, Liira H, et al (2026)

Integrated miRNAome-transcriptome analyses identify an immuno-hematopoietic subcluster in patients with long COVID.

The Journal of allergy and clinical immunology pii:S0091-6749(26)00439-2 [Epub ahead of print].

BACKGROUND: Persistent symptoms following SARS-CoV-2 infection, termed post-COVID-19 condition or long COVID (LC), impose substantial psychological and socioeconomic burdens. However, miRNA-mRNA interactions underlying LC heterogeneity remain incompletely defined.

OBJECTIVE: To determine whether integrative blood miRNA-mRNA profiling identifies molecular LC subclusters linked to clinical and immune-hematopoietic features.

METHODS: We performed integrated miRNAome-transcriptome profiling of circulating blood RNA from individuals with LC and recovered controls. Differential miRNA and mRNA expression were assessed using LIMMA, and hierarchical clustering was used to define LC subclusters. Validated miRNA-mRNA interaction networks were constructed using miRNet. Clinical, functional, and biochemical parameters were compared between subclusters, and a random forest classifier was developed.

RESULTS: Clustering identified an immune-hematopoietic LC subcluster, LC1, characterized by extensive miRNA-mRNA dysregulation, enrichment of erythropoietic, platelet, and immune pathways, and biochemical alterations including lower plasma sodium and elevated fibrin D-dimer and thrombin time. Compared with LC2, LC1 showed persistently greater symptom burden, functional impairment, reduced quality of life, lower resilience, and higher anxiety/depressive symptoms. Potential confounding by age, sex, comorbidities, and selected medication use was evaluated. Network and co-expression analyses identified regulatory nodes enriched for viral infection and natural killer cell activation pathways. A random forest classifier incorporating nine miRNAs and LRRFIP2 achieved an AUROC of 0.91 for LC1, distinguishing LC1 from LC2 and recovered controls.

CONCLUSION: LC comprises biologically and clinically distinct subclusters shaped by coordinated miRNA-mRNA remodeling. The immune-hematopoietic LC1 subtype supports biomarker-based stratification of patients with persistent physiological and clinical impairment.

RevDate: 2026-06-20

Xu H, Du C, Chen Y, et al (2026)

EGCG inactivates tumor necrosis factor-alpha (TNFα) by inducing its higher-order assembly.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 159:158437 pii:S0944-7113(26)00668-9 [Epub ahead of print].

BACKGROUND: Tumor necrosis factor-alpha (TNFα) is an important therapeutic target for treating a range of inflammatory and autoimmune disorders. The TNFα trimer functions by interacting with its receptors (TNFRs) on the immune cell surface and triggers downstream intracellular signaling. (-)-Epigallocatechin-3-gallate (EGCG) is the primary bioactive polyphenol compound in green tea. Our previous study found that EGCG can inhibit TNFα activity; however, the underlying molecular mechanism remains unclear.

PURPOSE: In this study, we investigated the interaction between EGCG and TNFα to elucidate the mechanism by which EGCG inactivates TNFα.

METHODS: EGCG-treated TNFα was analyzed using size exclusion chromatography (SEC), multiangle light scattering (MALS), and cryo-electron microscopy (cryo-EM). Mass spectrometry (MS), chemical modifications, and cell-based assays were further conducted to assess the function of the endogenous cysteines.

RESULTS: EGCG induces assembly of TNFα trimers into higher-order aggregation states, characterized as a non-strictly defined oligomerization. This process involves reorganization of the endogenous disulfide bond (C69-C101) through reduction and subsequent oxidation reactions. The resulting oligomers are incapable of triggering TNFα-TNFR signaling, and capping the free cysteines in TNFα abrogates the inhibitory effect of EGCG.

CONCLUSION: These findings reveal the molecular basis for the beneficial effect of EGCG in TNFα-associated inflammatory and autoimmune diseases, giving a new support to the consumption of regular green tea as a dietary therapy. This approach may be particularly relevant in the post-COVID-19 context for managing long COVID symptoms linked to elevated TNFα levels.

RevDate: 2026-06-20

Mateu L, Hansen LL, Carmezim JP, et al (2026)

Blinded 2-Year Longitudinal Evaluation of SARS-CoV-2 Antigenemia in Long COVID.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases pii:S1198-743X(26)00326-5 [Epub ahead of print].

OBJECTIVES: SARS-CoV-2 antigens have been detected in plasma months after acute infection, but their long-term dynamics and clinical relevance remain unclear. We aimed to assess the persistence and clinical specificity of plasma SARS-CoV-2 antigenemia over two years following acute infection.

METHODS: We conducted a 2-year longitudinal study involving 425 adults who developed Long COVID (n=167) or fully recovered from acute Covid-19 (n=148), and uninfected controls (n=110). Plasma samples were collected at 6-12 months and 18-24 months post-infection. SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens were quantified using the ultra-sensitive Simoa® platform blinded for clinical features. SARS-CoV-2 specific humoral responses, including neutralizing antibodies, were also assessed.

RESULTS: At 6-12 months, SARS-CoV-2 antigenemia (any antigen) was detected in 31% of individuals with Long COVID, in 20% of those fully recovered and in 5.4% of uninfected controls. By 18-24 months, positivity declined to 3%, 0% and 0%, respectively. Full spike was the most frequent antigen detected, whereas S1 was rarely observed and nucleocapsid was absent in recovered participants. Antigenemia was not associated with number or type of persistent symptoms, antibody titers, including neutralizing capacity, or vaccination status.

CONCLUSION: SARS-CoV-2 antigens circulate in plasma up to one year after infection in a minority of individuals, regardless of whether they develop Long COVID or not, and become rarely detectable later on. Therefore, current evidence does not support its use to guide clinical monitoring or treatment decisions in Long COVID.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Zhang R, Gu X, Zhang H, et al (2025)

Long COVID: current research and future directions.

Infectious diseases & immunity, 5(4):260-271.

Long coronavirus disease (COVID) is defined as the continuation or development of new symptoms three months after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and that last for at least two months, with no other explanation for their cause. This disease includes various clinical manifestations that affect multiple organ systems, such as complications in respiratory, cardiovascular, neurological, and musculoskeletal systems. The most commonly reported symptoms include fatigue, cognitive dysfunction, dyspnea, and chest pain; however, the prevalence and severity of these symptoms vary greatly among individuals. The underlying mechanisms of long COVID are complex and multifaceted, encompassing viral persistence, immune system dysfunction, mitochondrial abnormalities, endothelial impairment, and alterations in the microbiome. Further, long COVID has imposed a significant burden on individuals, healthcare systems, and the economy by impairing an individual's quality of life and functional capacity, thereby increasing costs and demand for care and rehabilitation services. This review summarizes the definition, phenotypes, mechanisms, and current treatment advancements of long COVID and highlights specific research directions for future investigation.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Liu S, Guo Y, FS Wang (2025)

Viral persistence in long COVID: Research advances and treatment strategies.

Infectious diseases & immunity, 5(4):272-288.

Although the coronavirus disease 2019 (COVID-19) pandemic has ended, the enduring health impacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continue to garner global attention, as approximately 10% of patients develop long COVID (post COVID-19 condition). The epidemiological characteristics and symptoms of long COVID have been reported, and various pathogenic hypotheses have been proposed. Recent evidence suggests that SARS-CoV-2 nucleic acids or fragments persist in some patients post-infection and that these are correlated with long COVID symptoms. This review focuses on clinical studies linking SARS-CoV-2 persistence to long COVID symptoms, and explores the relationship between viral persistence and other etiological hypotheses, such as immune dysregulation, vascular issues, coagulation dysfunction, microbiome dysbiosis, brainstem/vagus nerve signaling dysfunction, and latent virus reactivation. Futhermore, treatment strategies for long COVID are proposed based on current clinical trials of antiviral and immune modulation therapies. Understanding the role of viral persistence in long COVID pathogenesis is critical for developing targeted therapies and improving clinical management of this debilitating condition.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Soni J, Ali R, Chattopadhyay P, et al (2026)

Intracellular microbial shifts during COVID-19 infection and longitudinal recovery revealed by single-cell RNA sequencing.

iScience, 29(7):116344.

Host-microbe dynamics during SARS-CoV-2 Omicron variant infection and recovery remain poorly understood, particularly regarding intracellular microbial communities in immune cells. We performed single-cell RNA sequencing of 191,417 peripheral blood mononuclear cells (PBMCs) from 57 individuals (9 healthy, 24 Omicron-infected, 16 recently recovered, 8 long-recovered) using the BD Rhapsody platform. Microbial signatures identified with PathogenTrack revealed elevated alpha diversity in acutely infected and recently recovered groups, driven by opportunistic pathogens such as Escherichia coli and Providentia stuartii. In contrast, healthy and long-recovered individuals displayed commensal-dominated profiles, notably Streptomyces sviceus, indicative of restored balance. Functional analysis showed persistent microbial signatures, including Clostridium botulinum's rpoB in B cells of long-recovered individuals, broad expression of E. coli stress gene sgrR, and Mycoplasma hyopneumoniae's rpsO across 12 immune subsets. Notably, S. sviceus dnaK was exclusive to healthy monocytes. These results suggest enduring intracellular microbial influences, implicating them in long-COVID pathophysiology with potential therapeutic relevance.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Ansone L, Pelcmane L, Brīvība M, et al (2026)

Immunothrombosis in hospitalized COVID-19 patients identified by multiomics profiling and linked to postacute complications.

iScience, 29(7):116326.

Post-acute sequelae of COVID-19 (PASC) disproportionately affect hospitalized patients and require improved molecular characterization to inform patient management. Here, we performed a prospective longitudinal multi-omics study of hospitalized COVID-19 patients, analyzing whole blood transcriptomics, targeted urine metabolomics, kidney injury biomarkers, and electronic health record-based outcome stratification across acute illness, one-month, and three-month recovery time points. Interconnected immunothrombosis-related pathways dominated the acute phase, while most immune and metabolomic pathways partially normalize. However, patients who developed long COVID exhibited a distinct blood transcriptional signature at three months consistent with an endothelial-associated activation profile, including platelet reactivity, complement dysregulation, and low-grade vascular inflammation, distinguishing them from fully recovered individuals. This multi-omics approach identifies clinically measurable biomarkers associated with longitudinal molecular trajectories and supports post-acute risk stratification.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Sheng J, Song Y, Zhang A, et al (2026)

Unraveling the cardiovascular burden of long COVID: symptom profiles, underlying mechanisms, and clinical management insights.

Frontiers in cardiovascular medicine, 13:1786633.

BACKGROUND: Long COVID refers to multisystem symptoms that begin within 3 months of COVID-19 infection and persist for at least 2 months. To this day, Long COVID remains a challenging clinical entity and a substantial global health burden, with cardiovascular sequelae representing a prominent component. Patients frequently report a range of symptoms including chest pain, palpitations, fatigue, and exercise intolerance.

OBJECTIVE: This mini review aims to synthesize current evidence on the symptom profiles, underlying mechanisms, and clinical management of Long COVID-related cardiovascular complications.

METHODS: We conducted a targeted narrative literature search of PubMed/MEDLINE, Web of Science, Scopus, Embase, and Google Scholar for articles published up to January 2026 using combinations of "Long COVID," "post-acute sequelae of SARS-CoV-2 infection," "cardiovascular," "myocarditis," "endothelial dysfunction," "microvascular injury," "dysautonomia," "vaccination," and "SARS-CoV-2 variants." Original studies, systematic reviews, meta-analyses, clinical guidance documents, and selected mechanistic studies were prioritized, whereas non-peer-reviewed preprints and single case reports were included only when they provided unique mechanistic or hypothesis-generating information. Eligibility was based on cardiovascular relevance to Long COVID; studies without post-acute or cardiovascular relevance were excluded.

RESULTS: The evidence indicates that cardiovascular Long COVID is heterogeneous and multifactorial, involving viral persistence, immune dysregulation, endothelial dysfunction, microvascular injury with hypercoagulability, autonomic nervous system dysregulation, and risk modification by acute disease severity, vaccination status, and SARS-CoV-2 variant period. Current management strategies remain primarily symptom-based, with emphasis on cardiovascular risk assessment, mechanism-informed phenotyping, graded rehabilitation, dysautonomia-directed treatment, and multidisciplinary follow-up.

CONCLUSIONS: Cardiovascular Long COVID is a heterogeneous burden driven by interacting mechanisms. Current evidence supports subgroup-based risk stratification and mechanism-informed management, while future studies should standardize endpoints and evaluate mechanism-targeted interventions.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Wolf DA, Monnat SM, Gutin I, et al (2026)

Long COVID and Subjective Wellbeing among U.S. Working-Age Adults.

Research square pii:rs.3.rs-9707617.

Background Long COVID symptoms can persist for months or years, impeding daily functioning, employment, and social relationships. While prior research links long COVID to adverse clinical mental health outcomes, less attention has been paid to broader subjective wellbeing-including life satisfaction, happiness, and hopefulness. This study examined associations between long COVID symptoms and subjective wellbeing among U.S. working-age adults, including whether associations differ by sex. Methods This cross-sectional analysis used data from the 2023 and 2024 National Wellbeing Surveys (NWS), a weighted survey of U.S. adults aged 18-64 (N = 13,990). We operationalized long COVID as having experienced any of eight symptoms (fatigue, forgetfulness, shortness of breath, joint or muscle pain, rapid heartbeat, dizziness, depression or anxiety, and exercise-exacerbated symptoms), a symptom count, and a dose-response specification. Subjective wellbeing measures include life satisfaction, happiness, and hopefulness. We estimated regression models for the full sample and separately by sex, adjusting for sociodemographic and economic characteristics. We reported results using point estimates, odds ratios (ORs) and 95% Confidence Intervals (95% CI). Results Nearly 39% (95% CI: 37.5,40.2) of respondents reported at least one long COVID symptom, with females reporting higher prevalence (43.1%) than males (34.7%) and more symptoms (mean = 1.80) than males (mean = 1.35). Long COVID was significantly associated with lower wellbeing across all three subjective wellbeing outcomes for both sexes. A dose-response pattern was observed: more symptoms were associated with progressively worse wellbeing. Among individual symptoms, depression or anxiety and cognitive difficulties exhibited the strongest negative associations with subjective wellbeing. Despite reporting higher long COVID prevalence, females had higher predicted life satisfaction and hopefulness than males at most levels of long COVID severity. Conclusions In this nationally representative sample of U.S. working-age adults, long COVID was associated with reduced subjective wellbeing across multiple operationalizations of long COVID and dimensions of wellbeing for both males and females. These findings underscore that the burden of long COVID extends beyond clinical mental health outcomes to broader evaluative and experiential dimensions of wellbeing, suggesting long COVID may represent an important population health risk for diminished quality of life.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Brewer SE, Fisher ME, Zittleman L, et al (2026)

Health equity-oriented design for dissemination: products and impact of rapid community translation for COVID-19 vaccine promotion.

Frontiers in public health, 14:1721808.

BACKGROUND: Public health messaging often falls short of the needs of underserved and minority communities, missing the mark on translating information that captures cultural, linguistic, or community relevance to influence health behaviors. Rapid community translation (rapid-CT) is an adaptation of the Boot Camp Translational method for community engagement in translating medical evidence into community health promotion messages and interventions. This paper describes the dissemination of materials from a rapid-CT of messages promoting COVID-19 vaccination among children and adults, boosters, and Long COVID messages.

METHODS: This project engaged five disproportionately impacted Colorado communities: urban and rural Latino/a/x, urban Black/African American, rural African immigrant, and urban American Indian/Alaska Native communities to conduct three cycles of about 6 week each of rapid-CT over 2021-2022. Each cycle of rapid-CT was led by 2 trained facilitators, usually one academic and one community partner. The process involved: (1) determining the role of partners and fostering partnerships; (2) describing the innovation, rationale, and evidence; (3) identifying the intended audience, message, timing, and format for dissemination; (4) selecting the communication and distribution channels; (5) identifying barriers and facilitators to dissemination, and (6) evaluating and refining the dissemination process. Dissemination was examined via tracking spreadsheet and impact was examined through surveys (recollection of seeing the materials, attitudes about COVID vaccinations, and vaccine status) and team de-briefing.

RESULTS: We engaged 126 unique community members and 15 facilitators. Within each cycle, rapid-CT communities co-created distinctive campaigns including messages, materials, and dissemination strategies. Each rapid-CT group identified anticipated and actual barriers and facilitators to the dissemination of messages and materials. Each group also demonstrated impact with metrics ranging from views of online videos or marketing materials to distributions of items promoting the message (e.g., 1,000 stickers distributed), although capacity to assess impact was a varied and the changing evidence and related to COVID-19 vaccination presented challenges.

CONCLUSION: Rapid-CT was effective for engaging communities in co-creating distinct messages and communication strategies tailored to their community's needs and populations. Rapid-CT is well-suited to message creation for dynamic public health emergencies. Future use of Rapid-CT should set clear expectations for time commitment of community partner and establish prospective evaluation plans in addition to community-developed plans.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Capistrano KJ, Naqvi RA, Elshourbagy S, et al (2026)

Salivary microRNA Profiling of Long COVID Subjects Reveals Host-Encoded Regulators of Inflammation and Viral Persistence.

bioRxiv : the preprint server for biology pii:2026.06.07.730729.

Periodontal disease and COVID-19 are linked by convergent immunoinflammatory pathways, yet the molecular basis of their interaction remains poorly defined. Here, we present a comprehensive salivary microRNA profile from individuals with prior SARS-CoV-2 infection, sampled approximately 3-6 months after diagnosis and meeting criteria for long COVID, providing new insight into the post-viral oral microenvironment. Salivary miRNA sequencing revealed widespread repression in patients with PD, consistent with persistent immune dysregulation. Relative to COVID-19-negative/PD-negative controls, thirty-two miRNAs were differentially expressed in COVID-19-positive/PD-positive individuals, all significantly downregulated. A similar signature was observed in a post-vaccination cohort for the selected dysregulated miRNAs. Integrative pathway analyses identified these miRNAs as regulators of core inflammatory circuits, including Ras, MAPK, and NFκB signaling, converging on IL-1β- and TNF-centered networks relevant to both PD and COVID-19. Mechanistically, restoration of three downregulated miRNAs, miR- miR-30e-3p 106-3p-3p, and miR-652-3p attenuated NFκB activation and cytokine release in TLR-stimulated human oral keratinocytes, while their functional suppression using inhibitors potentiates inflammation. These miRNAs were also predicted to target SARS-CoV-2 spike and nucleocapsid transcripts, an interaction validated by dual-luciferase reporter assays. Their overexpression further reduced spike and nucleocapsid expression in Beta- and Omicron-infected epithelial cells, as measured by flow cytometry and RT-qPCR confirming host miRNAs as potent endogenous SARS-CoV-2 restriction factor. Together, these findings identify salivary host miRNAs as mechanistic regulators of oral inflammatory tone and viral persistence, establishing a molecular link between periodontal inflammation and post-COVID oral pathology.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Espín E, Yang C, Shannon CP, et al (2026)

Pilot longitudinal integrated transcriptomic-metabolomic study reveals immune and metabolic signatures in non-hospitalized healthcare workers with long COVID.

Frontiers in cellular and infection microbiology, 16:1808564.

INTRODUCTION: Long COVID affects hundreds of millions of individuals worldwide, yet its underlying biological mechanisms remain incompletely understood, and the absence of validated biomarkers continues to limit diagnosis and clinical management. Most biomarker studies have focused on hospitalized patients with severe disease, leaving non-hospitalized populations, particularly healthcare workers, who are at high occupational risk, underrepresented. This gap may constrain the identification of biomarkers relevant to milder but persistent post-acute phenotypes.

METHODS: We performed integrated transcriptomic and metabolomic profiling in a longitudinal cohort of non-hospitalized healthcare workers with long COVID (N = 12), primarily presenting with fatigue and brain fog, and matched controls who recovered from SARS-CoV-2 infection without sequelae (N = 35). Whole-blood RNA extracted from PAXgene tubes was profiled using the NanoString nCounter PanCancer Immune Panel. Serum metabolites collected pre- and post-infection were analyzed using untargeted ultra-high-performance liquid chromatography-mass spectrometry. Differential expression and metabolite abundance were assessed using linear models with false discovery rate correction. Significant features were integrated using network- and pathway-based approaches to identify coordinated immune-metabolic alterations in long COVID.

RESULTS: Transcriptomic analysis identified 63 differentially expressed genes, including neutrophil-associated markers such as S100A8 and LY96, consistent with activation of innate inflammatory pathways. Metabolomic profiling identified 24 annotated metabolites, with oxoglutarate exhibiting a distinct longitudinal trajectory, increasing in long COVID cases while decreasing in controls. Integrated network analysis highlighted central nodes (APP, RELA, ATF2, HLA-B) and revealed pathway-level convergence on necroptosis and serotonergic synapse signaling, suggesting coordinated immune-metabolic dysregulation rather than isolated gene-level effects.

DISCUSSION: These findings generate hypotheses regarding potential links between persistent innate immune activation, metabolic reprogramming, and neurocognitive or systemic symptoms in long COVID. The observed signatures suggest immune-metabolic perturbations involving neutrophil-associated inflammatory pathways and broader cellular stress responses. However, given cohort size, platform-specific constraints, and cross-cohort heterogeneity, these signals should be interpreted at the pathway level and considered candidate mechanisms requiring validation in larger, independent cohorts of non-hospitalized individuals.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Cheng ZS (2026)

Prioritizing long COVID related single nucleotide polymorphisms by mining genome-wide association studies of COVID-19 susceptibility and hospitalization.

Frontiers in systems biology, 6:1797543.

Long coronavirus disease (COVID) presents a significant public health challenge, characterized by over 200 reported symptoms across multiple organ systems. Genetic studies of long COVID have been hindered by the disorder's symptom heterogeneity and the limited sample size of available datasets. To overcome these challenges, a proxy-based, hypothesis-generating strategy was conducted to prioritize candidate risk loci on studying long COVID by analyzing GWAS summary statistics of coronavirus disease 2019 (COVID-19) susceptibility, hospitalization, and long COVID from the COVID-19 Host Genetics Initiative (Release 7), resulting in 62 candidate loci represented by independent variants. These variants are grouped into three categories: (1) severe COVID-19-specific variants, exhibiting reduced signals in non-hospitalized cases; (2) variants associated with both severe and mild COVID-19, and (3) non-hospitalization-specific variants associated with mild cases. Evaluation using recently published long COVID datasets from the same consortium demonstrated that most candidate variants displayed weaker associations around nominal significance, with only a single genome-wide significant signal at rs12660421 of FOXP1. Integrative gene expression analyses further demonstrated that genes near these candidate loci exhibits weaker associations with long COVID than with acute COVID-19 outcomes. However, broader phenome-wide analyses identified 52 genes linked to traits relevant to long COVID. These candidate loci are warranted for further investigation.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Lees CR, Morad T, Webb M, et al (2026)

Long COVID sequelae in heart transplant recipients.

JHLT open, 13:100600.

Post acute sequelae of SARS-CoV-2 infection (also known as Long COVID) have been defined as symptoms that persist after 3 months from initial acute episode of COVID-19. While the pathophysiology and mechanisms that cause Long COVID are hypothesized as secondary to persistent inflammation and immune dysregulation, the burden of this disease remains difficult to estimate due to varied symptomatology. Solid-organ transplant recipients in particular remain a vulnerable population that has been disproportionately affected by the COVID-19 pandemic, and the impact of Long COVID among orthotopic heart transplant recipients (OHTRs)-a patient population on chronic immunosuppressive therapy-remains incompletely characterized. We sought to evaluate patient-reported Long COVID symptoms between OHTRs compared to patients with baseline cardiomyopathy. We conducted a prospective survey-based study of adult OHTRs and cardiomyopathy control patients with documented SARS-CoV-2 infection. Participants completed telephone surveys, which included questionnaires of symptoms, quality of life (QOL), and mental health assessment. Between-group differences were evaluated using multivariable models adjusting for baseline characteristics. Our results show that the prevalence of Long COVID symptoms did not significantly differ between OHTRs and patients with cardiomyopathy. Dyspnea was reported more frequently in the non-OHTR group; however, this association was attenuated after adjusting for a higher burden of underlying pulmonary disease. No evidence of increased overall symptom burden was observed among OHTRs. In this first comparative analysis of Long COVID among OHTRs and control cardiomyopathy patients, OHTRs demonstrated no increase in symptom burden and may experience fewer persistent symptoms.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Wang L, Hu X, D Yan (2026)

Integrative perspectives on electroacupuncture modulation of vagal-cholinergic and neuro-immune-metabolic regulation in long COVID.

Frontiers in integrative neuroscience, 20:1775007.

Long COVID is increasingly recognized as a multisystem condition involving persistent inflammation, autonomic dysregulation, and metabolic disturbance. The vagus nerve-mediated cholinergic anti-inflammatory pathway (CAP) provides a biologically plausible link between neural regulation and immune homeostasis, while metabolic pathways involving AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) are closely related to mitochondrial function and energy balance. In this review, we synthesize evidence from neuroscience, immunology, and metabolic research to investigate how electroacupuncture (EA) may modulate vagal-cholinergic signaling and the downstream inflammatory and metabolic processes associated with long COVID. Experimental studies indicate that EA can influence CAP-related mechanisms, including α7 nicotinic acetylcholine receptor (α7nAChR)-mediated inhibition of NF-κB/NLRP3-related inflammatory signaling, and may also regulate AMPK-SIRT1-PGC-1α-associated metabolic pathways. Although clinical evidence is more indirect, it suggests that electroacupuncture may affect autonomic function, inflammatory markers, symptom burden, and neurophysiological regulation. To support a balanced interpretation, we organize the evidence in this review into a framework based on levels of evidence, which distinguishes direct preclinical findings from indirect clinical indicators and associations used to generate hypotheses. This framework highlights the potential convergence of vagal-cholinergic anti-inflammatory regulation and metabolic recovery pathways, while recognizing that several proposed connections-particularly those linking CAP-related signaling to improvements in long COVID symptoms-require further validation. Overall, this review provides a structured basis for future mechanistic studies and phenotype-oriented clinical trials evaluating EA as a neuromodulatory strategy for long COVID and related chronic inflammatory conditions.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Oka N, Nakamura K, Hirahata K, et al (2026)

Donepezil ameliorates fatigue and depression in PASC patients with HHV-6B SITH-1-induced acetylcholine deficiency.

Frontiers in pharmacology, 17:1807203.

INTRODUCTION: The pathogenesis of post-acute sequelae of SARS-CoV-2 infection (PASC) remains poorly understood, and no effective treatment has been established. Reactivation of latent herpesviruses, particularly human herpesvirus 6B (HHV-6B), has been proposed as a possible contributor to the neuropsychiatric symptoms observed in PASC. SITH-1, a latency-associated protein expressed during HHV-6B reactivation in olfactory bulb astrocytes, induces specific antibody responses that can be detected in peripheral blood. Importantly, SITH-1 has also been identified as a risk factor for depression, suggesting a mechanistic link between HHV-6B reactivation and the development of neuropsychiatric symptoms.

METHODS: We measured serum anti-SITH-1 antibody titers in 156 PASC patients and compared them to healthy controls. In this PASC cohort, neuropsychiatric symptoms were assessed using numerical rating scales. In parallel, we developed a mouse model in which SITH-1 was transiently expressed in the olfactory bulb to assess its impact on brain function and behavior. We also conducted a subgroup analysis of a previously reported randomized clinical trial (RCT) of donepezil, stratifying PASC patients by anti-SITH-1 antibody status.

RESULTS: Anti-SITH-1 antibody positivity was observed in 62.8% of PASC patients, a significantly higher proportion than in controls. Seropositive patients exhibited more severe fatigue and depressive symptoms. In the mouse model, SITH-1 expression led to reduced acetylcholine production and depression-like behavior, both of which were ameliorated by donepezil. In the clinical trial subgroup of 73 PASC patients, 71.7% were seropositive for anti-SITH-1 antibodies. Among these individuals, donepezil significantly improved fatigue and depression scores, as measured by the Chalder Fatigue Scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS).

CONCLUSION: These findings suggest that HHV-6B reactivation in the olfactory bulb, as indicated by anti-SITH-1 antibody titers, may contribute to fatigue and depression in a subset of PASC patients. Donepezil may be effective in this subgroup, and these findings support the use of anti-SITH-1 antibody titers as a companion diagnostic marker for targeted treatment in PASC.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Axon DR, S Fenwick (2026)

Prevalence and Associations of Medical Expenditure Panel Survey-Defined Long COVID Among Adults: Cross-Sectional Study.

JMIR formative research, 10:e92323 pii:v10i1e92323.

BACKGROUND: Long COVID is a clinical condition that significantly influences quality of life, productivity, and morbidity in the individuals affected. Much of the research to date has examined medical comorbidities and their associations with long COVID, but there remains a substantial need to understand the social and behavioral factors associated with long COVID.

OBJECTIVE: The objective of this study was to investigate the prevalence and associations of Medical Expenditure Panel Survey (MEPS)-defined long COVID among adults in the United States through the application of the Andersen behavioral model.

METHODS: This cross-sectional database study used the 2022 MEPS dataset. Variables in this analysis were organized according to the Andersen behavioral model. The appropriate weighting variable was used to obtain weighted population-based estimates. Between-group differences (ie, those with MEPS-defined long COVID vs those without) were assessed using chi-square tests, and a multivariable binomial logistic regression model was developed to assess the association between each variable and having MEPS-defined long COVID.

RESULTS: A total of 11,266 individuals were eligible for inclusion in this study. This represented a weighted population of 256,500,584 American adults. Of these 11,266 individuals, 790 (7%; weighted population=18,397,214) had MEPS-defined long COVID, whereas 10,476 (93%; weighted population=238,103,371) did not. Variables identified that were statistically associated with having MEPS-defined long COVID among American adults included 3 predisposing variables (age, sex, and Asian race), 2 enabling variables (marital status and employment status), 3 need variables (number of chronic conditions, health status, and instrumental activity of daily living limitations), 1 personal health practices variable (ever receiving the COVID-19 vaccine), and 1 external environmental variable (south region).

CONCLUSIONS: The prevalence and factors associated with having MEPS-defined long COVID among American adults in this study offer insights to expand our limited understanding of the complex environmental and social factors associated with MEPS-defined long COVID. Further research is required among the long COVID population to better understand and differentiate the causes and consequences of this condition.

RevDate: 2026-06-22
CmpDate: 2026-06-22

Chen YH, Lin CH, Liu JH, et al (2026)

Effects of incentive spirometer training on dyspnea and functional status in patients with long COVID.

PloS one, 21(6):e0351553 pii:PONE-D-25-41209.

BACKGROUND: Since the emergence of Coronavirus Disease 2019 (COVID-19), it has become a global pandemic, profoundly affecting public health and daily life. Many recovering individuals report persistent or recurrent symptoms-fatigue, palpitations, cognitive impairment, shortness of breath, anxiety, and chest discomfort. These lingering effects impair work, daily function, and social interaction, placing a significant burden on individual quality of life and society.

OBJECTIVE: This study aims to evaluate the effectiveness of using an induced Incentive Spirometer as a respiratory training tool to relieve long COVID symptoms.

METHODS: This study, conducted from July 1, 2023, to May 11, 2024, at a regional teaching hospital in northern Taiwan, involved participants who had recovered from COVID-19 within the past year and had at least one long COVID respiratory symptom. Participants were assigned to one waiting control group and four experimental groups based on recovery time: within 3 months (Experimental Group 1), 3-6 months (Experimental Group 2), 6-9 months (Experimental Group 3), and 9-12 months (Experimental Group 4). The waiting control group received no interventions, while the experimental groups underwent inspiratory training using an induced Incentive Spirometer three times a week for 6 weeks (30 repetitions per session). Assessments were conducted before and after the intervention. Primary outcomes were the Dyspnoea-12 scale and Post-COVID-19 Functional Status scale. Secondary outcomes included the 6-minute walk distance and CaO₂.

RESULTS: Ninety participants were enrolled, with five withdrawing, leaving 85 for final analysis. After 6 weeks of intervention, the waiting control group showed no significant changes in dyspnea (p = 0.463) or post-COVID-19 functional status (p = 0.343). In contrast, all experimental groups showed significant improvements. Dyspnoea-12 scale scores improved in Experimental Groups 1 (p < 0.001), 2 (p = 0.008), 3 (p = 0.011), and 4 (p = 0.001). The Post-COVID-19 Functional Status scale also showed improvements in all Experimental Groups (Group 1: p < 0.001, Group 2: p = 0.003, Group 3: p = 0.002, and Group 4: p = 0.011). Significant improvements in 6-min walk distance were observed in some experimental groups, improvements were seen in Experimental Groups 1 (p < 0.001), 2 (p = 0.027), 3 (p = 0.68), and 4 (p = 0.172). No significant changes in CaO2 were observed (pre-test, p = 0.872 and post-test, p = 0.585).

CONCLUSION: Respiratory training using an induced Incentive Spirometer may help alleviate dyspnea and improve post-COVID-19 functional status in individuals with Long COVID. Earlier intervention appeared to yield better outcomes, although improvements were also observed even 9-12 months after infection. However, further studies with comprehensive pulmonary assessments are needed to confirm these findings.

CLINICAL TRIAL NUMBER: NCT06165835, registered on 9 December 2023.

RevDate: 2026-06-22

Haldar D, Rout HS, Gupta S, et al (2026)

Long Coronavirus Disease 2019 and its Association with Noncommunicable Diseases: A Bibliometric Analysis.

Indian journal of public health [Epub ahead of print].

BACKGROUND: Long coronavirus disease 2019 (COVID-19), or post-acute sequelae of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection, has emerged as a major global health concern. Its relationship with noncommunicable diseases (NCDs) remains underexplored despite overlapping pathophysiological pathways.

OBJECTIVES: This bibliometric analysis evaluates global research trends, key contributors, and thematic clusters at the intersection of long COVID-19 and NCDs.

MATERIALS AND METHODS: A comprehensive search was conducted in Scopus and Web of Science databases using relevant MeSH and/or keyword combinations. Bibliometric indicators including publication trends, prolific authors and country collaboration networks analyzed using VOSviewer and R Bibliometrix.

RESULTS: Fifty-five relevant publications were identified between 2020 and 2024. Research activity peaked in 2023, dominated by studies on cardiovascular, metabolic, and respiratory comorbidities. Collaboration networks showed strong contributions from China, the United States, and the United Kingdom. However, limited representation was observed from low- and middle-income countries (LMICs).

CONCLUSION: This bibliometric analysis highlights a growing but uneven global research landscape linking long COVID-19 and NCDs. Cardiovascular and metabolic disorders have received significant attention, whereas neurological and oncological sequelae remain underinvestigated. Future research must strengthen interdisciplinary collaboration and address the inequitable participation of LMICs.

RevDate: 2026-06-22

Vogel JM, Jenkins T, Cerda M, et al (2026)

Sustained Reduction in Cardiopulmonary Fitness in Long COVID: A Report from the RECOVER-adult Cohort Study.

JACC. Advances, 5(7):102923 pii:S2772-963X(26)00344-3 [Epub ahead of print].

BACKGROUND: Long-term effect of COVID-19 (Long COVID) may persist for months or years after SARS-CoV-2 infection, but longer-term cardiopulmonary manifestations have not been previously reported.

OBJECTIVES: The objective of the study was to characterize cardiopulmonary function after SARS-CoV-2 infection in a digital health substudy of the nationwide Researching COVID-19 to Enhance Recovery Adult Cohort Study.

METHODS: Associations between wearable sensor device measures of cardiopulmonary fitness and survey-derived Long COVID symptoms were estimated over a 6-month window at least 6 months after infection using linear regression models adjusted for wear time, age, sex, race/ethnicity, and body mass index.

RESULTS: Among 1,475 participants (72% female, 65% non-Hispanic White) a median of 21 months (IQR: 15-31 months) after infection, 498 (34%) had high symptom burden as characterized by the Researching COVID-19 to Enhance Recovery Long COVID Research Index (LCRI). High LCRI (vs low LCRI) was associated with significantly lower heart rate variability (-4.4 ms; 95% CI: -6.5 to -2.4; P < 0.001), higher resting heart rate (+1.5 beats/min [+0.7 to +2.4]; P < 0.001), fewer metabolic equivalent of task minutes (-96.3 [-128.8 to -63.8]; P < 0.001), lower step counts (-1,624 steps/day [-1,952 to -1,296]; P < 0.001), and lower activity levels (-7.9 minutes/day very or fairly active [-10.9 to -5.0]; P < 0.001). Hierarchal clustering analysis identified two subphenotypes with abnormal cardiovascular measures associated with low quality of life scores.

CONCLUSIONS: Long COVID is associated with worse cardiovascular fitness. Additional studies are needed to determine if Long COVID is a novel risk factor for incident cardiovascular disease.

RevDate: 2026-06-19

Hooven TA (2026)

A controlled longitudinal study clarifies the contours of pediatric long COVID.

Pediatric research [Epub ahead of print].

RevDate: 2026-06-19

Pence S, Zhuang Y, Shi F, et al (2026)

Racial Disparities and Social Determinants of Long COVID in the United States: Evidence from the 2022 Behavioral Risk Factor Surveillance System.

Journal of racial and ethnic health disparities [Epub ahead of print].

BACKGROUND: While racial disparities in COVID-19-related outcomes and the role of social determinants of health (SDOH) are well documented, few studies have examined how race/ethnicity and SDOH jointly influence the occurrence of long COVID (LC) and the variation in its primary symptoms.

METHODS: Using 2022 Behavioral Risk Factor Surveillance System data, we estimated LC prevalence across racial/ethnic groups and calculated a SDOH summary score (0-10), with higher scores indicating greater exposure to adverse SDOH. Logistic regressions were employed to assess associations of SDOH and race/ethnicity with the presence of LC and primary LC symptoms. Adjusted average marginal effects (AMEs) were calculated to quantify differences in LC prevalence across SDOH levels and racial/ethnic groups.

RESULTS: Among 92,109 respondents who tested positive for COVID-19, 20,393 (22.14%) reported experiencing LC. Compared to non-Hispanic Whites, non-Hispanic Black (adjusted odds ratio [aOR] = 0.82, 95% confidence interval [CI]: 0.668-0.999) and Asian (aOR = 0.58, 95% CI:0.370.89) individuals were less likely to report LC. Higher SDOH scores were associated with increased LC risk, with aOR (95%CI) being 1.47(1.28-1.69), 1.56(1.29-1.87), 2.26(1.80-2.83), and 3.21(2.65-3.89) for scores of 1, 2, 3, and ≥ 4, respectively, compared with a score of 0. Compared to White individuals, Black and Hispanic respondents had higher odds of reporting joint/muscle pain (aOR = 3.03, 95%CI: 1.49-6.18, and OR = 3.11, 95%CI: 1.84-5.25, respectively). Higher SDOH scores were linked to increased risk of joint/muscle pain, dizziness, and post-exertional symptoms, but decreased risk of taste/smell loss.

CONCLUSION: Greater SDOH burden was associated with higher LC prevalence and variation in primary symptoms, with effects differing across racial/ethnic groups. These findings highlight the importance of addressing social conditions in efforts to reduce LC disparities.

RevDate: 2026-06-18
CmpDate: 2026-06-18

Hirabayashi K, Lorman V, Wuller S, et al (2026)

Evaluation of steroids for acute COVID in the prevention of long COVID in children: An EHR and pediatric cohort study from the RECOVER Initiative.

PloS one, 21(6):e0350888.

BACKGROUND: Studies have shown that use of immunomodulators during the acute phase of SARS-CoV-2 infection may decrease development of post-acute sequelae of SARS-CoV-2 (PASC) or long COVID; however, such studies have not been conducted in children.

OBJECTIVE: Evaluate the effectiveness of steroid use during the acute phase of SARS-CoV-2 infection in preventing long COVID in children.

METHODS: We conducted a retrospective cohort study using target trial emulation methodology to compare children and youth who did and did not receive dexamethasone, prednisone, prednisolone or methylprednisolone within 12 days of SARS-CoV-2 infection. Inverse propensity of treatment weighting was used to balance covariates between treated and untreated patients in hospitalized and outpatient groups. The primary outcome was the development of PASC in the 1-6 months following acute infection using a computable phenotype definition. Secondary outcomes included respiratory, musculoskeletal, gastrointestinal and neurological subphenotypes and the PASC ICD-10-CM diagnosis code. We calculated hazard ratios from Cox proportional models with 95% confidence intervals.

RESULTS: From a starting cohort of 854,128 children/youth, of whom 768,845 (90.0%) were outpatients and 85,283 (10.0%) were inpatients at the time of SARS-CoV-2 infection, the weighted outpatient cohort included 22,085 steroid-treated children and 20,373 in the non-steroid group. Following weighting, the hospitalized cohort included 11,250 steroid-treated children and 10,340 untreated children. In hospitalized patients, there were no significant treatment differences in the development of PASC in the 1-6 months following acute SARS-CoV-2 infection except for a lower risk of gastrointestinal PASC in treated patients (HR: 0.58; [95% CI: 0.39-0.85], p = 0.01). In outpatients, no treatment differences were observed in the development of PASC subphenotypes.

CONCLUSIONS: Steroids administered during acute SARS-CoV-2 infection did not lead to a decreased risk of PASC, with the exception of gastrointestinal presentations. Additional studies are needed to confirm the benefit of steroids and other immunomodulators in preventing long COVID.

RevDate: 2026-06-18

Jokela-Pansini M, Cousins O, Dainow J, et al (2026)

From research method to community resource: Co-developing a body mapping toolkit for peer support with Long Covid patients.

Social science & medicine (1982), 404:119331 pii:S0277-9536(26)00407-7 [Epub ahead of print].

The paper describes the development of a Body Mapping Toolkit for Long Covid Patients, co-created in collaboration with the patient-led organisation Long Covid Support. We discuss how the use of body mapping, a participatory and arts-based research method, can support a more holistic and embodied understanding of Long Covid attentive to the way illness experiences are shaped by patients' social, cultural, and economic contexts. We further demonstrate how, through collaboration with patient organisations, body mapping might be extended beyond this research application to create spaces for peer support within the Long Covid community. Toolkit redevelopment was informed by three online body mapping workshops with a total of 13 participants, two follow-up feedback workshops and a feedback survey, all conducted in 2024. Our findings demonstrate that online body mapping workshops provide a safe space and opportunity to process experiences through creativity and storytelling and an accessible and flexible way for people with particularly challenging symptoms and restrictions to discuss their experiences with others. We also reflect on some of the limitations and challenges we encountered, and how we sought to mitigate these. The article thereby: (i) contributes to current approaches in medical humanities, medical anthropology and health geography concerned with centering patient narratives of illness experience; (ii) illustrates the value co-producing knowledge and resources with patients; and (iii) offers an example of how creative methods can be drawn on as a resource for both research and peer support.

RevDate: 2026-06-19

Reeves J, Daynes E, Janaudis-Ferreira T, et al (2026)

Physiotherapy management of Long-COVID: an evidence-based approach.

Brazilian journal of physical therapy, 30(4):101609 pii:S1413-3555(26)00034-1 [Epub ahead of print].

BACKGROUND: Long-COVID is a heterogenous, episodic, and multisystemic condition which can result following infection with a novel pathogen, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Whilst a precise pathophysiological cause is unknown, several mechanisms are hypothesised, each with plausible scientific rationale. Most people experiencing persistent symptoms following COVID-19 infection recover, yet some experience severe and debilitating illness for years after infection. Strategies to manage the sequelae of Long-COVID can improve the lives of sufferers.

OBJECTIVE: To describe the physiotherapy management of Long-COVID based on current evidence.

CONTENT: Those with 'invisible illness' (illness without outwardly visible signs), such as Long-COVID, often report stigmatisation and scepticism from healthcare systems. Validation of the experience of those with Long-COVID is therefore crucial to ensure patient-centred care. Thorough patient assessment is required to provide tailored management approaches given the diversity of Long-COVID presentations. Red flags that may contraindicate certain rehabilitation approaches (particularly exercise-based interventions) or that warrant further investigation should be considered. Assessments of fatigue, post-exertional malaise, respiratory symptoms, neurocognitive symptoms (i.e., brain fog), physical function, and orthostatic intolerance are strongly recommended. Management strategies may involve pacing and energy conservation techniques, pulmonary rehabilitation, inspiratory muscle training, dysfunctional breathing retraining, lifestyle and dietary strategies to manage orthostatic intolerance, and return-to-work planning.

CONCLUSION: Physiotherapists are well positioned to deliver individualised, patient-centred, and validating care based on best available evidence.

RevDate: 2026-06-19

Thomas N, Huang K, Schneider-Futschik EK, et al (2026)

Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research.

Frontiers in neuroendocrinology pii:S0091-3022(26)00038-5 [Epub ahead of print].

Hormonal dysregulation is increasingly reported in ME/CFS and Long COVID, yet the broader role of neuroendocrine disruption in these conditions remains underexplored. While changes in steroid, peptide, and neuropeptide hormones have been identified, these findings are often considered in isolation and without attention to their timing or integration within broader physiological systems. The hypothalamic-pituitary axes regulate endocrine, immune, autonomic, nervous, and metabolic functions, systems commonly affected in both conditions, yet their circadian and menstrual dynamics are rarely investigated. In this review, we examine the evidence for neuroendocrine dysfunction in ME/CFS and Long COVID, focusing on hormone output, functional assays, receptor expression, and the coordination of endocrine biorhythms. Sex hormone signalling emerges as a key area of vulnerability, particularly given the female predominance in both conditions and the complexity of reproductive hormone regulation. We argue that accurate hormone measurement and time-structured sampling, including circadian and menstrual rhythms, are essential for detecting meaningful biological differences. By embedding chronobiology-aware, dense-sampling strategies and integrating multi-omic analyses into multi-system study designs, we outline a framework for investigating dynamic endocrine mechanisms underlying symptom variability and multisystem dysfunction, which may ultimately support the development of more targeted, personalised interventions.

RevDate: 2026-06-17

Peter N, IS Ramya (2026)

Central sensitization in long COVID: Associations with autonomic symptom burden, cerebral hypoperfusion, and neuroinflammation.

Journal of the neurological sciences, 488:126058 pii:S0022-510X(26)00340-0 [Epub ahead of print].

BACKGROUND: The mechanisms driving the broad spectrum of Long COVID symptoms-such as fatigue, brain fog, pain, and dysautonomia-remain uncertain. This study investigated central sensitization (CS) as a potential contributor to symptom burden in patients with Long COVID. We aimed to examine its association with symptom severity, as well as objective cerebrovascular, autonomic, and inflammatory markers.

METHODS: A total of 169 consecutive patients with Long COVID referred for evaluation of orthostatic intolerance underwent assessment using the Central Sensitization Inventory, symptom burden surveys (autonomic: COMPASS-31; sensory: NTSS-6; global health: PROMIS), autonomic function testing (deep breathing, the Valsalva maneuver and head-up tilt test with transcranial Doppler and capnography monitoring), and skin biopsies for small-fiber assessment.

RESULTS: CS was present in 81% of participants. Patients with CS were more often female (79.6% vs. 53.1%, p = 0.004) and had higher rates of anxiety, depression, fibromyalgia and headaches, as well as a significantly greater autonomic, sensory and global health symptom burden (all p < 0.001). Compared with patients without CS, they also exhibited a greater decline in orthostatic cerebral blood flow velocity (-25.53% ± 11.19 vs. -22.09% ± 10.53, p = 0.038) and higher interleukin-6 levels (p = 0.041). Autonomic failure, most commonly of mild grade, occurred at similar frequency in both groups (84.7% vs. 84.4%, p = 0.999). Skin biopsies demonstrated a comparable prevalence of abnormal findings in both groups (50.8% vs. 52.0%, p = 0.999).

CONCLUSION: Central sensitization appears highly prevalent among patients with Long COVID and may contribute to their multisystem symptomatology. Cerebral hypoperfusion, and neuroinflammation may constitute pathophysiological mechanisms underlying central sensitization in this population.

RevDate: 2026-06-17

Guedj E, Horowitz T, A Verger (2026)

Brain [18F]FDG PET in Encephalitis and Postinfectious Neurocognitive Syndromes.

PET clinics pii:S1556-8598(26)00048-9 [Epub ahead of print].

Brain [18F]FDG PET can reveal metabolic abnormalities that precede, exceed, or clarify structural MR imaging findings. Among inflammatory brain diseases, the strongest clinical rationale is currently in autoimmune encephalitis, where fluorodeoxyglucose (FDG) PET increases diagnostic sensitivity, supports syndrome-oriented metabolic pattern recognition, and may contribute to selected follow-up. In viral encephalitis, use is selective rather than routine. In post-coronavirus infectious disease (COVID) condition and related postinfectious syndromes, FDG PET may support biological stratification and differential diagnosis in a subset of patients. Interpretation remains highly dependent on clinical context and methods. Translocator protein (TSPO) PET adds mechanistic information on neuroimmune activation but belongs mainly to the research domain.

RevDate: 2026-06-18

Kabir F, Yin KN, Jeffree MS, et al (2026)

Effectiveness of adapted physical activity and therapeutic exercise programme in improving chronic fatigue syndrome in long COVID, delivered via hospital-based rehabilitation versus telerehabilitation.

Trials pii:10.1186/s13063-026-09769-2 [Epub ahead of print].

BACKGROUND: Long COVID is a prevalent condition characterised by pain, fatigue, disability, and a multitude of health issues. There are various treatment options for managing long COVID symptoms, including non-pharmacological interventions like physiotherapy and rehabilitation, which can be effectively delivered either in institutional care settings or via telerehabilitation.

METHODS: This three-arm randomised controlled trial included 145 participants selected from a population-based cohort in eight administrative divisions in Bangladesh. Participants aged 18 and above diagnosed with chronic fatigue syndrome (CFS) secondary to long COVID were included and history of fatigue, cardiovascular, neuro-musculoskeletal, or respiratory diseases, or red flag signs were excluded. Participants were allocated to three groups: hospital-based rehabilitation (HBR), telerehabilitation (TR), or a home programme (HP). Interventions consisted of an individualised exercise programme. The HBR and TR groups received physiotherapist-supervised sessions with sessions lasting 45 min, twice weekly for 8 weeks. And the HP group performed exercises independently following structured instruction. Fatigue, the primary outcome, was measured using the Chalder fatigue scale, while secondary outcomes were quality of life measured using the 36-item Short Form Survey (SF-36), disability-adjusted life years (DALYs), and cardiorespiratory parameters (blood pressure, pulse rate, oxygen saturation, and lung capacity).

FINDING: Between 1st July 2023 and 31st December 2023, 145 participants were enrolled, with a mean age of 46.1 ± 6.7 years. After 8 weeks of intervention, the among-group within-group comparison showed a significant difference in fatigue level (HBR: P < 0.001; TR: P < 0.001; HP: P < 0.321), physical functioning (HBR: P < 0.001; TR: P < 0.001; HP: P < 0.057), and episodic disability (HBR; TR; HP: P < 0.001) among the participants when comparing them between the groups. In multiple comparisons, results showed that differences were observed in the Chalder fatigue scale, physical functioning, and episodic disability between all groups. Hospital-based rehabilitation showed a lower mean score compared to telerehabilitation (p < 0.0001) and the home programme (p < 0.0001). Additionally, telerehabilitation was significantly better than the home programme (p < 0.0001), indicating hospital-based rehabilitation's superior efficacy in reducing fatigue, improving physical function, and reducing disability.

CONCLUSION: Physiotherapy as hands-on implementation in a hospital setting was substantially more effective than telerehabilitation. Training healthcare professionals to improve accessibility to rehabilitation would help mitigate the consequences of long COVID-19.

TRAIL REGISTRATION: The trial was registered with the clinical trial registry of India (CTRI/2023/03/050808. Registered on 17/03/2023).

RevDate: 2026-06-16
CmpDate: 2026-06-16

Helmsdal G, Kristiansen MF, Gaard EK, et al (2026)

Persistent symptoms, cognitive impairment, and clinical predictors of long COVID one year after Omicron infection: A clinical case-control study from the Faroe Islands.

PloS one, 21(6):e0351564 pii:PONE-D-25-65362.

BACKGROUND: Six years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.

OBJECTIVES: The aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.

METHODS: We conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).

RESULTS: A total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13-1.30, p < 0.001). Sub-analysis showed particularly strong associations for fatigue, cognitive impairment, neurological symptoms, and symptoms from the cardiopulmonary and musculoskeletal systems. Both mental impairment and fatigue independently predicted long COVID (aOR 1.27, 95% CI 1.14-1.42, p < 0.001, and aOR 1.27, 95% CI 1.11-1.46, p < 0.001, respectively). Additionally, a higher number of self-reported infections during the follow-up period increased the odds of long COVID (aOR 1.57, 95% CI 1.06-2.34, p = 0.025), though this was not reflected in antibiotic use. Finally, blood analyzes showed that lower white blood cell counts were associated with increased odds of long COVID in women, but not in men, however the clinical significance of this finding remains uncertain.

CONCLUSIONS: One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.

RevDate: 2026-06-16
CmpDate: 2026-06-16

Kim SJ, J Kim (2026)

Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis.

PloS one, 21(6):e0351506 pii:PONE-D-25-56606.

BACKGROUND: Post-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.

OBJECTIVES: In this study, we aimed to classify the symptom profiles of Korean adults with PASC using latent profile analysis (LPA) and examine the differences in HRQoL and associated factors between the identified profiles.

METHODS: We conducted an online survey of 629 adults in Korea who experienced persistent symptoms ≥12 weeks after coronavirus disease (COVID-19) diagnosis. Symptom burden was assessed using the Long COVID Symptom Tool (26 items), and HRQoL was measured using the SF-36 v2®. LPA was performed to identify the symptom subgroups. One-way analysis of variance (ANOVA) and multiple linear regression were used to compare HRQoL across profiles and explore predictors.

RESULTS: A four-class model provided the best fit: Class 1 (Low symptom, 23.3%), Class 2 (Moderate multisystem, 44.1%), Class 3 (Fatigue/post-exertional malaise dominant, 15.9%), and Class 4 (High multisystem burden, 16.7%). HRQoL differed significantly between classes (p < .001), with a clear gradient of decreasing scores from low to high symptom burden. The independent predictors of lower HRQoL included lower education, presence of chronic disease, poor subjective health, hospitalization during acute infection, and prolonged symptom persistence. The model explained 32.9% of the variance in HRQoL.

CONCLUSIONS: Korean adults with PASC exhibit heterogeneous symptom patterns that substantially affect their HRQoL. The identification of distinct symptom profiles supports the need for tailored interventions, including rehabilitation, cognitive training, and psychological support. Our findings provide crucial evidence for developing Korean population-specific screening tools and management guidelines for PASC.

RevDate: 2026-06-17
CmpDate: 2026-06-17

Inderyas M, Thapaliya K, Marshall-Gradisnik S, et al (2026)

Investigation of BOLD signal intensities in long COVID patients using 7T functional MRI.

Brain, behavior, & immunity - health, 54:101266.

Long COVID is increasingly associated with disruption in brain homeostasis, manifesting as severe neurological dysfunction, brain fog and cognitive impairment. This present study investigated localised cognitive deficits in long COVID patients by examining brain blood oxygenation-level-dependent (BOLD) signal activity using ultra-high-field 7 T (7T) task-based functional magnetic resonance imaging (fMRI). Whole-brain BOLD signal differences were assessed across 19 long COVID patients, and 27 healthy controls (HC) including 12 COVID-recovered (Cov-RHC) and 15 COVID-19-naïve HC (nHC). 225 fMRI volumes were acquired during the Stroop colour-word task. Functional and anatomical images were processed using SPM12 to extract the BOLD signal intensity time course from whole-brain voxels for inferences between cohorts during task-fMRI. Significantly low BOLD activation in long COVID patients was observed compared to Cov-RHC in the anterior cingulate cortex (p = 0.002, cluster size=650, Z-value = 4.67), and the precuneus (p = <0.001, cluster size = 1893, Z-value = 4.67). Furthermore, BOLD intensities in precuneus showed a negative association with self-reported pain scores (p = 0.040) and the duration of illness (p = 0.03) in long COVID patients, suggesting significant correlation between BOLD signal and an increase in duration of illness and pain levels. No statistically significant BOLD differences were observed for inter-group comparisons between nHC vs. long COVID, and nHC vs. Cov-RHC. Response times to incongruent (p = 0.002) and congruent task stimuli (p = 0.001) significantly varied between nHC and long COVID cohorts, demonstrating overall faster information processing by nHC. Reduced BOLD signals to 'core' brain regions in long COVID imply reduced cognitive control by intrinsic networks that mediate information processing, cognitive and executive functions due to perturbations linked to cerebral blood flow, oxygenation status, and ongoing neuroinflammation.

RevDate: 2026-06-15
CmpDate: 2026-06-15

Chetty L, Reddy P, Ramdin S, et al (2026)

Long term cardiometabolic outcomes in COVID positive patients.

Journal of public health research, 15(2):22799036261445801.

In South Africa, approximately 4.5 million confirmed COVID-19 cases and 103,000 deaths have been noted. Symptoms range from being asymptomatic, mild respiratory issues to severe multi-organ failure and consequent death. Cardiometabolic risk factors, viz., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), atherosclerosis, chronic kidney disease, hypertension, heart failure, and obesity, are flagged as the most prevalent comorbidities associated with the risk of severe COVID-19 and death. Many who have recovered from hospitalization continue to experience lingering symptoms known as long COVID, which have been linked to new-onset cardiometabolic disorders (CMD). This narrative review thus focusses on the clinical factors and the patient burden of diabetes mellitus and hypertension as two of the most commonly observed CMD, and aims to raise awareness regarding possible cardiometabolic complications. The findings expand the existing literature on the cardiometabolic effects of COVID-19, concentrating on outcomes observed more than three months after the acute phase of the illness.

RevDate: 2026-06-15

Jiang S, Loomba J, Sharma S, et al (2022)

Vital Measurements of Hospitalized COVID-19 Patients as a Predictor of Long COVID: An EHR-based Cohort Study from the RECOVER Program in N3C.

Proceedings. IEEE International Conference on Bioinformatics and Biomedicine, 2022:3023-3030.

It is shown that various symptoms could remain in the stage of post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as Long COVID. A number of COVID patients suffer from heterogeneous symptoms, which severely impact recovery from the pandemic. While scientists are trying to give an unambiguous definition of Long COVID, efforts in prediction of Long COVID could play an important role in understanding the characteristic of this new disease. Vital measurements (e.g. oxygen saturation, heart rate, blood pressure) could reflect body's most basic functions and are measured regularly during hospitalization, so among patients diagnosed COVID positive and hospitalized, we analyze the vital measurements of first 7 days since the hospitalization start date to study the pattern of the vital measurements and predict Long COVID with the information from vital measurements.

RevDate: 2026-06-16

da Silva Almeida I, de Jesus Ferreira LG, Vaz MA, et al (2026)

Muscle fatigue in patients with severe long COVID: A 2-year follow-up study.

PM & R : the journal of injury, function, and rehabilitation [Epub ahead of print].

BACKGROUND: Fatigue is recognized as one of the most persistent and debilitating symptoms of long COVID, affecting both functionality and quality of life. However, its long-term effects, especially beyond the first year after infection, remain poorly understood.

OBJECTIVE: To investigate self-reported fatigue and muscle fatigability in individuals with severe long COVID compared to matched healthy controls at 18 and 24 months post infection.

DESIGN: Longitudinal observational study.

SETTING: The study was conducted at the Laboratory of Muscle and Tendon Plasticity at the University of Brasília.

PARTICIPANTS: Twenty survivors of severe-COVID and 20 age- and gender-matched controls underwent repeat assessments at 18 and 24 months following hospital discharge.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Perceived fatigue was measured using the Fatigue Severity Scale, functionality with the 30-second sit-to-stand test, muscular dimensions and quality assessment were evaluated through ultrasound-derived thickness and echogenicity, and muscle fatigability was assessed using torque, torque-time integral, and rate of force development. The generalized estimating equations method was used with "group" and "assessments" as factors, with the least significant difference test identifying specific differences. Chi-square test compared categorical variables.

RESULTS: The severe-COVID group showed consistently poorer functional performance (mean difference: 2.65 [0.45-4.85], p = .018), higher perceived fatigue (2.25 [1.54-2.95], p < .001) and lower rate of force development (-103.68 [-177.22 to -30.13], p = .006) compared to controls. No significant differences were observed in muscle thickness or echogenicity between groups.

CONCLUSION: Long COVID is associated with sustained fatigue, impaired neuromuscular function, and reduced physical performance up to 2 years after infection. These findings underscore the need for long-term, mechanism-based rehabilitation strategies targeting central fatigue and neuromuscular function.

TRIAL REGISTRATION: NCT04961255.

RevDate: 2026-06-16

Montgomery A, Erdmann N, Jinright A, et al (2026)

Mental and Physical Health Predictors of Return-to-Work Outcomes among Individuals with Long COVID Symptoms.

International journal of behavioral medicine [Epub ahead of print].

BACKGROUND: Emerging evidence shows that infectious diseases, such as COVID-19, can lead to chronic health conditions. Long COVID symptoms such as fatigue, cognitive impairment, and psychological distress can significantly hinder return-to-work, complicating recovery and rehabilitation. This study explores how these persistent symptoms affect work outcomes to inform clinical and policy interventions supporting affected individuals.

METHODS: We conducted a single-site study of patients following acute SARS-CoV-2 infection (N = 206, 128 employed prior to infection). Participants reported symptoms that occurred anytime between COVID-19 infection and survey completion and their work status. A classification decision tree was generated with return-to-work status as an outcome.

RESULTS: Among 128 participants, 65% (n = 83) returned to their usual work duties after COVID-19 infection, with a mean recovery time of 21 days. Twenty percent (n = 25) resumed work under modified conditions (e.g., reduced hours or remote work) after a mean of 43 days, and 10% (n = 13) were unable to return due to persistent symptoms. The top five important variables that predicted work status post-COVID-19 infection were mental health, physical health, emotional distress, recovery days, and back pain.

CONCLUSIONS: Overall, global mental and physical health status are stronger predictors of return-to-work status after COVID-19 infection than most individual long COVID symptoms, with the exceptions of emotional distress and back pain symptoms. Patients who have issues with mental health, physical health, emotional distress, long recovery time, and back pain are a primary group that needs support with transitioning back to work.

RevDate: 2026-06-16
CmpDate: 2026-06-16

Tc HD, S C, J K, et al (2026)

Post COVID REspiratory mechanisms and the efficacy of a breathing exercise intervention for DYsregulated breathing (Remedy): A feasibility RCT study.

Chronic respiratory disease, 23:14799731261454679.

BackgroundDysregulated breathing is a major cause of persisting breathlessness for many people following acute COVID-19 illness. There is little evidence to support the use of breathing interventions within this population.MethodsA feasibility study was conducted to investigate the potential role of supervised, remote online yogic breathing as an intervention, compared to usual care. The intervention was a six-week group programme, in which they were encouraged to attend bi-weekly. Primary outcomes of attendance, completion and acceptability were recorded and a survey following the intervention. Secondary measures of breathlessness and physical function were collected.ResultsOf 122 people invited who had reported dysregulated breathing at the time of clinical consult, 40 consented and 34 were randomised (Intervention n=17, usual care n=17), 33 had initial assessment (n=16 and n=17) and with post-intervention outcomes available in n=13 and n=14, respectively. Of the 13 in the intervention arm, 5 people completed >75% of sessions and the post intervention assessment. The median number of sessions attended per participant was 7. No safety issues were recorded. The survey (n=13) of the actual intervention highlighted it was well received but there was limited options for attending. Although some breathlessness measures improved in the people receiving the intervention, there was no significant difference when comparing the intervention to usual care arms.ConclusionsThe feasibility of the study was limited in this select population of people after COVID-19 with dysregulated breathing. The intervention was well received, but attendance at all the sessions was challenged by the limited options for the sessions.

RevDate: 2026-06-16
CmpDate: 2026-06-16

Gale N, Beetham H, Lyden S, et al (2026)

Community-delivered hyperbaric oxygen therapy for people affected by long COVID: a pilot study.

British journal of nursing (Mark Allen Publishing), 35(12):626-632.

Long COVID is an umbrella term commonly used to describe a range of symptoms, such as chronic fatigue, 'brain fog' and breathlessness, that persist for at least 12 weeks after acute COVID-19. Although there are currently no effective treatment options, emerging research indicates that hyperbaric oxygen therapy (HBOT) may help improve many major long COVID symptoms, in the short term. This mixed-methods pilot study aimed to explore the impact of HBOT, delivered in a community setting, on key long COVID symptoms. Findings indicate that fatigue, breathlessness and quality of life improved in participants who completed 4 weeks of HBOT. Although experiences of therapy were positive, with perceived improvements in significant symptoms, attending regular sessions was often difficult, due to the ongoing challenges associated with long COVID. This preliminary study suggests HBOT has potential to improve key symptoms in people with long COVID but further controlled studies are now needed.

RevDate: 2026-06-16
CmpDate: 2026-06-16

Kehl-Floberg K, Freisberg E, Pop-Vicas A, et al (2026)

Long COVID risk by pre-infection symptoms and functional status: A retrospective cohort study of data from the All of Us Research Program.

PloS one, 21(6):e0330793 pii:PONE-D-25-41757.

IMPORTANCE: Over seven million U.S. adults experience persistent health issues after COVID-19, known as "long COVID". Although multiple guidelines recommend the inclusion of functional status in long COVID diagnostic criteria, more evidence is needed to guide this recommendation. This study explored the adjusted odds of developing long COVID by pre-infection symptoms and functional status, and the feasibility of estimating functional status using health records data.

DESIGN & METHODS: Retrospective cohort study of U.S. adults with history of COVID-19 enrolled in a multicenter national cohort study through July 2022 (All of Us Controlled Tier CDR 7.0), using diagnostic, procedure, and billing codes from the health record, and baseline survey responses. The risk of long COVID was estimated using logistic regression by pre-infection (-5 years) incidences of (a) at least one symptom common in long COVID, and (b) functional impairment, and adjusted for disease and demographic characteristics.

RESULTS: n = 65,464 met inclusion criteria; n = 40,655 had post-infection occurrences of at least one symptom (long COVID group), n = 24,809 had none (recovered). Adjusted odds ratios of developing long COVID increased with older age, female sex, Black racial identity, earlier variant, non-vaccination, lower pre-infection self-reported mental and cognitive health, and number of pre-infection symptoms. Adjusted odds were not significantly affected by any single pre-infection symptom, self-rated physical ability, or EHR-derived indicators of prior functional impairment.

CONCLUSIONS: In this model, there were no significant differences in risk of long COVID based on either pre-infection total incidences of long COVID symptoms (compared to the average of 4) or pre-infection functional impairment. This suggests that long COVID was associated with a change from baseline functioning and health, including in people with pre-infection incident symptoms and functional impairments. The impacts of co-occurring pre-infection symptoms requires further investigation. Both harmonized electronic health records data and patient-reported outcomes contribute important data for developing the diagnostic utility of functional status changes in long COVID.

RevDate: 2026-06-12

Bird L (2026)

Pathological potential of autoantibodies in long COVID.

Nature reviews. Immunology [Epub ahead of print].

RevDate: 2026-06-13

Xie X, Zhao Z, Q Wu (2026)

Quality and reliability of short videos about long COVID on bilibili and tiktok: cross-sectional study under health community construction background in China.

BMC public health pii:10.1186/s12889-026-27621-9 [Epub ahead of print].

BACKGROUND: Long COVID, characterized by persistent symptoms such as fatigue and cognitive impairment, continues to pose a global public health burden. Bilibili and TikTok are major platforms for public health information; however, the lack of systematic evaluation contributes to low-quality information and may hinder effective health management. We aimed to evaluate the quality and reliability of long COVID-related videos on these platforms.

METHODS: This cross-sectional study analyzed long COVID-related videos from Bilibili and TikTok. Inter-rater reliability was assessed using Cohen's kappa coefficient. Quality and reliability were evaluated using the Global Quality Score (GQS) and modified DISCERN (mDISCERN). Multivariate linear regression was performed to identify the independent predictors of video quality.

RESULTS: The median GQS and mDISCERN scores were both significantly higher for Bilibili than for TikTok (P = 0.016 and P = 0.039, respectively). Professional-source videos showed significantly higher quality than non-professional ones (P < 0.001). Regression analyses revealed that a professional source was the strongest independent predictor of both GQS and mDISCERN scores (all P < 0.001). Video duration and shares were significantly, albeit weakly, associated with the GQS, whereas other engagement metrics were not.

CONCLUSIONS: The overall quality of long COVID videos was suboptimal. Professional source was the primary independent predictor of higher quality, while engagement and duration showed limited influence. Strengthening platform review mechanisms and promoting evidence-based information are needed to improve public health communication.

RevDate: 2026-06-13

Wu JW, Chen ST, Chang FC, et al (2026)

Cerebral arteriopathy and its role in persistent post-COVID headache and brain fog: a quantitative study.

European archives of psychiatry and clinical neuroscience [Epub ahead of print].

BACKGROUND: Headache and brain fog are common after COVID-19 infection, and inflammation and vasculopathy might be the potential underlying mechanisms. This study aimed to delineate the extent and impact of cerebrovascular involvement in patients with persistent long-COVID syndrome in a large Asian cohort.

METHODS: We prospectively collected data from patients with persistent (≥ 3 months) post-COVID headache or brain fog, and controls were free from neurological symptoms within 3 months after COVID-19 resolution. The anterior and posterior Focal Cerebral Arteriopathy Severity Score (FCASS) was used to assess the severity of arteriopathy and was modified to account for bilateral involvement (total score: anterior: 0-40; posterior: 0-52). Symptom severity was assessed using monthly headache days, Migraine Disability Assessment (MIDAS), and brain fog severity scale (0-10).

RESULTS: A total of 108 patients (M: F = 27:81) were divided into four groups based on symptoms categories. The presence of more symptom categories was associated with higher anterior-FCASS (combined 6.6 [2.1] vs. headache 3.6 [1.6] vs. brain-fog 4.7 [1.7] vs. control 0.8 [0.6], p < 0.001 by one-way ANOVA) and a posterior-FCASS (combined 5.5 [2.2] vs. headache 4.2 [1.6] vs. brain-fog 4.4 [2.3] vs. control 0.8 [0.8], p < 0.001 by one-way ANOVA). Pure brain- fog was more likely have predominance of anterior circulation involvement than pure headache (80.8% vs. 48.0%, p = 0.020), but the severity of brain fog was correlated with only the posterior-FCASS (Pearson's r = 0.338, p = 0.009) rather than the anterior-FCASS (Pearson's r = 0.173, p = 0.195).

CONCLUSIONS: Anterior circulation arteriopathy and hypoperfusion may underlie persistent post-COVID brain fog. However, post-COVID headaches may not depend solely on changes in intracranial vessels.

RevDate: 2026-06-13

Broughan J, Xie Y, Carberry C, et al (2026)

Long covid and general practice: a survey of patients in the Republic of Ireland.

Irish journal of medical science [Epub ahead of print].

BACKGROUND: Long Covid is a multi-factorial condition impacting millions globally.

AIMS: (1) To describe the demographic and health profiles of adults who have or have had Long Covid, and (2) examine their experiences of Long Covid healthcare, particularly in general practice. A cross-sectional online survey was conducted in the Republic of Ireland in April 2025.

METHODS: Survey items investigated demographics, medical history, and experiences of Long Covid care. Data was analysed using descriptive statistics and qualitative analysis of open responses.

RESULTS: Of 222 (87.05%) eligible respondents, most were 35-64 years (n = 184, 82.14%), female (n = 177, 79.7%), and born in the Republic of Ireland (n = 193, 86.9%). Respondents reported wide-ranging multimorbidity and Long Covid symptoms. Many strongly agreed that their symptoms were severe (n = 196, 88.7%) and detrimental to quality of life (n = 200, 90.1%), physical (n = 202, 91%) and mental (n = 98, 45%) health. Long Covid commonly lasted more than three years (n = 169, 76.1%), indicating substantial long-term impact on daily functioning. Almost all consulted general practitioners for Long Covid care (n = 213, 95.9%). Nearly half (n = 95, 44.6%) were dissatisfied with current GP care, and many felt GPs lacked adequate knowledge of Long Covid (n = 127. 59.6%). Respondents supported proposed GP-based investigative and referral interventions, as well as affirming and advocacy-focused doctor-patient relationships.

CONCLUSIONS: Continued clinical and research efforts are needed to address future Long Covid care needs. With structured, informed, holistic, and multidisciplinary care, general practice can make a positive contribution to the lives of those affected.

RevDate: 2026-06-14
CmpDate: 2026-06-13

Perumal N, Peine C, Steffen A, et al (2026)

Effectiveness of seasonal mRNA COVID-19 vaccination against post COVID-19 condition between July 2023 and September 2024 among adults aged ≥ 60 years in Germany: a population-based cohort study.

BMC infectious diseases, 26(1):.

BACKGROUND: Some individuals infected with severe acute respiratory syndrome coronavirus 2 experience long-term symptoms, termed post COVID-19 condition (PCC). Pandemic-era studies have demonstrated moderate effectiveness of COVID-19-vaccines in preventing PCC. However, as population immunity has evolved and variant-adapted vaccines have been introduced, estimates of vaccine effectiveness and disease frequency from the post-pandemic era are needed to guide policy-making and communication.

METHODS: We investigated whether one mRNA COVID-19 vaccine dose during the 2023/2024 season was associated with reduced PCC risk in the following six months among adults aged ≥ 60 years in Germany. We conducted a retrospective cohort study using nationwide, outpatient claims data and performed descriptive and Poisson regression analyses.

RESULTS: In our cohort of 19,121,674 patients, 3,437,701 (18.0%) received one dose of a seasonal COVID-19 vaccine and 36,830 fulfilled the PCC case definition (incidence: 0.2%). Vaccinated individuals were older (median age 75 years) compared to those who were not vaccinated (71 years), with a higher proportion being female (54% vs. 46% male). 0.08% of vaccinated patients were diagnosed with PCC during study follow-up, compared to 0.22% non-vaccinated. One vaccine dose was associated with lower risk (adjusted Risk Ratio 0.37; 95% CI 0.36-0.39) of receiving a PCC diagnosis at six months post-vaccination compared to no vaccination, translating to a vaccine effectiveness of 63%.

CONCLUSION: Our results demonstrate a low PCC-incidence and a strong protective association between seasonal COVID-19 vaccination and PCC during the first post-pandemic season. These findings can help improve acceptance of COVID-19-vaccines and support doctors' and patients' decision-making regarding vaccination.

RevDate: 2026-06-15
CmpDate: 2026-06-13

Matías-García PR, Lai L, Delerue T, et al (2026)

DNAm landscape up to 4 months post SARS-CoV-2 infection: insights from four population-based cohorts.

Clinical epigenetics, 18(1):.

BACKGROUND: Evidence for persistent epigenetic changes in individuals who had a mild SARS-CoV-2 infection is limited, as most DNA methylation (DNAm) studies to date have focused on either the acute phase of infection or on the months following infection in severe cases requiring hospitalization.

METHODS AND RESULTS: Using the Infinium Human MethylationEPIC BeadChip, we investigated blood DNA methylation (DNAm) up to four months after SARS-CoV-2 infection in cases and controls from four population-based cohorts (NAKO, Lifelines, CON-VINCE, and TiKoCo; n = 675) within the framework of the ORCHESTRA Consortium. We observed DNAm changes at 16 differentially methylated positions (DMPs) and 21 differentially methylated regions (DMRs), with 89% of these DMPs/DMRs hypomethylated in cases compared to age- and sex-matched controls. Genes mapped to these CpGs were annotated with Gene Ontology terms and pathways related to immune responses to viral infection. eQTM analyses in whole blood from an independent cohort (KORA FF4 study) produced 49 significant CpG-transcript pairs, including IFI44L and GNA12. Despite inter-individual variability and cohort heterogeneity, our findings regarding four DMPs (IFI44L, MX1, DDX60, and RABGAP1L) and two DMRs (PARP9 and GNA12) replicate changes described both in the acute phase of infection and at long-term follow-up. Differential methylation at other novel loci may reflect the systemic nature of post-infection epigenetic changes.

CONCLUSION: Our findings suggest moderate but persistent epigenetic changes up to four months after SARS-CoV-2 infection in mild cases from population-based cohorts. These changes partially mirror those reported during the acute phase of both mild and severe COVID-19 and overlap with pathways dysregulated in autoimmune, metabolic and neurological disease. Future research should examine epigenetic changes associated with persisting symptoms in long COVID, investigate downstream effects of DNAm changes on other -omics, and consider longer follow-up periods to further elucidate the molecular mechanisms underlying SARS-CoV-2 induced epigenetic changes.

RevDate: 2026-06-15

Sedgwick TA, Ulrich DM, Basurto KS, et al (2026)

Performance validity test failure rates among neuropsychological outpatients clinically referred for persistent Long COVID cognitive symptoms following mild SARS-CoV-2 disease severity.

Journal of clinical and experimental neuropsychology [Epub ahead of print].

OBJECTIVE: Persisting cognitive symptoms following SARS-CoV-2 infection (Long COVID) has become an increasingly common referral for neuropsychological evaluation. This study examined performance validity test (PVT) failure rates among adults referred for evaluation due to Long COVID cognitive complaints after mild SARS-CoV-2 disease severity.

METHOD: Data from 57 demographically diverse outpatients (72% female; Mage = 44.23; Meducation = 15.39 years) consecutively referred for a focused neuropsychological evaluation due to Long COVID cognitive symptoms were analyzed. The neuropsychological test battery included one freestanding (Test of Memory Malingering-Trial 1) and four embedded PVTs (Reliable Digit Span; California Verbal Learning Test-Brief Form Forced Choice; Brief Visuospatial Memory Test-Revised Recognition Discriminability; Stroop Color and Word Test-Word Reading T-Score), as well as a 11 neuropsychological test scores assessing the major domains of cognition, which were used to compute an overall neuropsychological test battery mean composite score.

RESULTS: Individual PVT failure rates ranged from 4% to 18%. Overall, 67% passed all PVTs, 24% failed one PVT, and 9% failed ≥ 2 PVTs. Patients failing two or more PVTs had an overall neuropsychological test battery mean performance that was significantly lower than the group failing one or zero PVTs and 1.0 standard deviations below the population mean. Patients with zero PVT failures also outperformed those with one PVT failure by 0.5 standard deviations. Nonsignificant differences in COVID disease characteristics emerged between groups.

CONCLUSIONS: The majority of patients (67%) passed all PVTs, with 24% of patients failing one PVT and 9% failing ≥ 2 PVTs. Future research is warranted to understand implications of a single freestanding PVT failure in this population, and to establish base rates of invalidity in Long COVID and among those with more severe initial COVID infection necessitating hospitalization and/or medical intervention. Such practices ensure accurate diagnosis, guide treatment, and improve the reliability of research on the cognitive sequelae of COVID-19.

RevDate: 2026-06-15
CmpDate: 2026-06-15

Seboka BT, Ma L, Magliano DJ, et al (2026)

The impact of post-acute sequelae of COVID-19 on cardiac function and structure: A systematic review and a hybrid individual participant data meta-analysis.

American journal of preventive cardiology, 27:101457.

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as Long COVID, affect a significant proportion of COVID-19 survivors, with evidence suggesting cardiovascular involvement. However, the nature, extent, and clinical significance of these alterations remain uncertain.

AIM: To synthesize evidence on structural and functional cardiac alterations in individuals with PASC compared with those without PASC.

METHOD: We systematically searched seven databases. Random-effects meta-analyses were performed and supplemented by individual participant data (IPD) analyses from three studies. Univariable and multivariable meta-regressions examined associations with study-level characteristics. Publication bias and evidence certainty were assessed using standard methods (funnel plots, Egger's test, trim-and-fill, and GRADE).

RESULTS: From 3580 records, 17 studies with 4852 participants (3173 PASC, 1679 controls) met the inclusion criteria. IPD analysis revealed an impairment in global longitudinal strain (GLS) (mean difference (MD) = 3.63 %) in individuals with PASC. When using categorical thresholds, 58 % of individuals with PASC had GLS < 16 %, indicating a significant prevalence of subclinical left ventricular dysfunction. Meta-analysis supported these findings, showing impaired GLS (MD = 1.07 %), along with reductions in left ventricular ejection fraction (MD = -1.30 %) and left ventricular end-diastolic volume (MD=-3.98 mL). Meta-regression showed that cardiac dysfunction was more frequently observed in individuals with older age, diabetes, and hypertension.

CONCLUSION: This review indicates that PASC is associated with modest, subclinical alterations in cardiac function. These alterations appear more pronounced in older adults and those with cardiometabolic comorbidities, highlighting the potential value of risk-stratified cardiovascular surveillance in individuals with PASC. The long-term clinical relevance of these changes remains unclear and warrants further study.

RevDate: 2026-06-15
CmpDate: 2026-06-15

Elbaroumi O (2026)

Approach to Fatigue in Primary Care: A Practical Diagnostic Framework for General Practitioners.

Cureus, 18(5):e108764.

Fatigue is one of the most common presenting complaints in primary care and poses a significant diagnostic challenge due to its multifactorial aetiology. While the majority of cases are benign and self-limiting, fatigue may also represent an early manifestation of serious underlying pathology. This review distinguishes between acute fatigue, typically transient and associated with intercurrent illness or lifestyle factors, and chronic fatigue, defined as fatigue persisting for six or more weeks, which is more likely to be multifactorial in origin. This narrative review aims to provide a practical and structured diagnostic framework for general practitioners to evaluate and manage fatigue effectively in the primary care setting. A narrative review of the literature was conducted using PubMed and Google Scholar. Searches were limited to articles published in English from 2010 onwards. Search terms included "fatigue," "primary care," "chronic fatigue," "myalgic encephalomyelitis," "post-viral fatigue," "sleep disorders," and "functional somatic syndromes." Seminal references predating 2010 were retained where no suitable replacement was available. This review did not employ a formal systematic search strategy, and no risk-of-bias assessment was performed, consistent with the narrative review format. Fatigue arises from a wide range of physical, psychological, and lifestyle-related causes, best understood through a three-tier classification: primary/idiopathic, secondary, and psychosocial. A systematic approach incorporating thorough history-taking, focused clinical examination, and judicious use of investigations is essential. Identification of red flag symptoms is critical to exclude serious conditions, including malignancy and chronic infections. A structured, patient-centred approach enables general practitioners to manage fatigue effectively while minimising unnecessary investigations and ensuring timely identification of serious disease.

RevDate: 2026-06-15
CmpDate: 2026-06-15

Groysman R (2026)

Long COVID as a network disorder: a mechanism-anchored framework for biological stratification and therapeutic targeting.

Frontiers in medicine, 13:1841690.

Long COVID is increasingly recognized as a biologically heterogeneous, multisystem condition with wide variability in symptom expression and treatment response. Although symptom-based phenotyping has advanced descriptive and epidemiologic understanding, similarity in clinical presentation does not necessarily imply shared upstream pathophysiology. Therapeutic cohorts defined solely by symptom clusters may therefore combine biologically distinct mechanisms, potentially diluting treatment effects and complicating interpretation of interventional trials. This manuscript proposes a complementary, mechanism-anchored framework centered on recurrent and biologically measurable domains: autonomic dysfunction, mitochondrial and bioenergetic impairment, endothelial and microvascular dysfunction, gut dysbiosis and barrier disruption, mast cell-mediated signaling, and neuroendocrine dysregulation. These primary domains are conceptualized as physiologically coherent systems capable of generating multisystem symptom patterns in biologically enriched subsets. Secondary amplifying processes, including persistent immune activation, viral antigen persistence without established replication, autoantibody formation, neuroinflammation, and sleep-related destabilization, are positioned as network-coupling processes that may sustain or amplify dysregulation across domains. Within a network-based framework, Long COVID is conceptualized as a network disorder in which interacting regulatory nodes are hypothesized to generate self-reinforcing feedback loops that maintain symptom persistence even after resolution of acute infection. The model accommodates heterogeneity across mechanisms and alternative explanatory hypotheses. It provides an operational structure for organizing mechanistic heterogeneity and generating testable predictions. A prototype, unvalidated screening instrument is included to illustrate a potential pathway toward mechanism-informed stratification and prospective trial enrichment. Future research should evaluate whether biologically enriched cohorts demonstrate differential therapeutic responsiveness compared with symptom-defined populations. Prospective validation using standardized physiological metrics will be essential to determine whether mechanism-guided stratification improves translational precision and clarifies actionable pathophysiology in Long COVID.

RevDate: 2026-06-15
CmpDate: 2026-06-15

Chowdhury MMH, Fontaine MN, Lord SE, et al (2026)

Aptamer-based analyses of plasma proteome in individuals with post-COVID condition who underwent tailored physical activity.

Frontiers in sports and active living, 8:1797346.

INTRODUCTION: Post-COVID condition (PCC) encompasses a spectrum of clinical symptoms affecting multiple organs that persist for >3 months after resolution of the initial SARS-CoV-2 infection. The complex nature of PCC symptoms makes it difficult to decipher the mechanistic basis of disease and establish efficient pharmacological interventions. However, non-pharmacological approaches such as personalized physical exercise regimen has been shown to improve the quality of life in PCC patients. Among the non-pharmacological interventions for PCC, physical rehabilitation, especially symptom-titrated physical exercise, has shown promise in restoring the quality of life but the underlying mechanisms are not yet elucidated. This personalized approach adjusts the physical training intensity according to patient's ability and tolerance levels.

METHODS: We had observed that individuals with PCC showed significant improvement following tailored physical exercise. Here the plasma samples obtained before and after the intervention was analyzed for a preselected panel of 1500 markers by SomaScan assay.

RESULTS: Proteins differentially expressed between the exercise and no-exercise groups suggest that the tailored exercise training drives distinct proteomic signatures involved in immune, vascular and oxidative stress pathways.

DISCUSSION: Despite the low sample numbers, our results indicate that the tailored exercise regimen resulted in significant alterations in biological pathways associated with PCC.

RevDate: 2026-06-12

Chen PC, Hsu YL, Wu LS, et al (2026)

Pediatric post-acute sequelae of SARS-CoV-2 infection in Taiwan: Insights from the DISCOVER cohort.

Pediatrics and neonatology pii:S1875-9572(26)00072-0 [Epub ahead of print].

The post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID, represent a multifaceted challenge in pediatric populations, characterized by symptoms persisting beyond the acute phase. In Taiwan, where early public health measures initially contained the pandemic, the 2022 Omicron surge prompted focused investigation into pediatric PASC, highlighting the critical need for longitudinal data in this specific demographic. To address this challenge, the Diagnosis and Support for COVID Children to Enhance Recovery (DISCOVER) study was established as a prospective, multidisciplinary cohort. By employing a multimodal approach, this study characterizes the clinical landscape of pediatric PASC in Taiwan through validated screening instruments, AI-driven diagnostics, and pulmonary assessments, while concurrently evaluating immune biomarkers, vaccination protection, and vitamin D intervention. This review synthesizes comprehensive findings from the cohort. While the acute phase of infection was predominantly mild, a substantial proportion of children experienced persistent multisystem symptoms, with fatigue, respiratory issues, and somatic complaints being most prevalent. Vaccination was found to significantly modify the disease trajectory, offering protection against subsequent gastrointestinal sequelae and preserving pulmonary function by mitigating small airway resistance. Furthermore, advanced diagnostic modalities, including impulse oscillometry and deep learning-assisted echocardiography, successfully unmasked subclinical organ dysfunction that conventional methods often failed to detect. Mechanistic investigations revealed that symptom severity was closely linked to elevated anti-nucleocapsid antibody titers, while markers of T-cell exhaustion evidenced persistent immune dysregulation, rather than ongoing viral replication. Notably, a preliminary single-center randomized controlled trial within this cohort provided early evidence that vitamin D supplementation may reduce the overall symptom burden and modulate pro-inflammatory cytokine profiles in children with PASC. Collectively, these findings underscore the multisystem nature and immune-driven mechanism of pediatric PASC, while highlighting the role of vaccination, advanced diagnostics, and targeted nutritional interventions in improving recovery. CLINICAL TRIAL REGISTRATION: NCT05426291 (ClinicalTrials.gov).

RevDate: 2026-06-11
CmpDate: 2026-06-11

Skipper L, Faghy MA, Thomas C, et al (2026)

Patient and public involvement and engagement in Long COVID research: embedding inclusion in research.

Research involvement and engagement, 12(1):.

BACKGROUND: Patient and public involvement and engagement (PPIE) is increasingly recognised as essential to ensuring that research is safe, inclusive and equitable, yet implementation often remains tokenistic or absent. In the ERASE-LC Trial, patients contribute as collaborators throughout the research process, helping to shape research questions, study design and delivery through their lived experience.

DISCUSSION: This paper provides examples that illustrate how lived experience can be integrated across the research lifecycle, from defining roles and responsibilities to enabling meaningful collaboration. Embedding PPIE within Long COVID research has informed approaches to engagement, accessibility, and participant safety. Although developed in the context of Long COVID, these approaches may be applicable to research in other chronic conditions and wider clinical research settings.

CONCLUSION: Drawing on reflections from our PPIE network and a case study from the Long COVID study, the ERASE-LC trial, we illustrate how inclusive and community-representative PPIE can be embedded in practice. These experiences highlight the value of flexible and accessible engagement approaches to inform co-produced recommendations for strengthening PPIE in health research.

CLINICAL TRIAL NUMBER: ClinicalTrials.gov, NCT05911906, 20/06/2023.

RevDate: 2026-06-11

Saleem S, Hussain A, Haroon M, et al (2026)

Dynamic microclot profiling: thromboelastography advances precision management in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.

Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis pii:00001721-990000000-00264 [Epub ahead of print].

Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share overlapping symptoms, and emerging evidence implicates persistent fibrinoid microclots in their pathophysiology, contributing to impaired microcirculation. This review explores the role of microclots and evaluates thromboelastography (TEG) as a potential diagnostic tool. A comprehensive literature review was conducted using major biomedical databases. Studies indicate microclots are prevalent in both conditions. Long COVID patients demonstrate a TEG profile of increased clot strength (maximum amplitude) and reduced fibrinolysis (LY30), suggesting a persistent hypercoagulable state. Despite its advantages in real-time assessment, TEG interpretation faces challenges from preanalytical variability and a lack of standardized protocols. Promising therapeutic trials, including anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase), require further validation. Technological advancements like AI-driven TEG analysis and portable devices could improve diagnostic precision. In conclusion, persistent microclots are a key pathophysiological feature. TEG provides a promising, novel approach for detecting coagulation abnormalities and could guide treatment, but requires standardization in future clinical trials. Future research should integrate multiomics biomarkers for precision therapeutics to improve patient outcomes.

RevDate: 2026-06-12
CmpDate: 2026-06-12

Mitkowski P, Leśniak M, Kobza D, et al (2026)

Immune Dysregulation After COVID-19: Longitudinal Analysis up to 9 Months.

International journal of molecular sciences, 27(11): pii:ijms27115137.

SARS-CoV-2 infection triggers a strong inflammatory response, and persistent symptoms after recovery are thought to reflect prolonged systemic dysregulation. However, mechanisms underlying long COVID remain unclear. This study evaluated longitudinal changes in cytokine hematological and biochemical parameters up to nine months after hospitalization for COVID-19 and examined their relationship with persistent symptoms, vaccination status, and the occurrence of comorbidities. Long COVID patients showed sustained elevations in IL-2, IL-6, IL-10, IL-17A, CXCL9, TNF-α, and IFN-γ compared with healthy controls, exhibiting heterogeneous temporal trajectories. Specifically, levels of IL-2, IL-10, TNF-α, and creatinine continued to increase over time, whereas IFN-γ, LDH, CCL2, CXCL9, and CXCL10 declined. Other parameters exhibited greater variability without a uniform longitudinal pattern. IL-6 demonstrated consistently high diagnostic performance in distinguishing individuals after COVID-19 from healthy controls (AUC > 0.82). Aging substantially affects cytokine profiles and systemic inflammatory status; therefore, residual age-related confounding cannot be fully excluded despite statistical adjustment. Although symptoms such as fatigue, cough, and dyspnea were still reported at nine months, no stable associations were identified between cytokine concentrations and clinical manifestations. These findings indicate that while immune alterations persist long after acute infection, systemic cytokine measurements alone may be insufficient to explain the presence or persistence of symptoms. The results suggest that long COVID reflects multifactorial processes extending beyond systemic inflammation and highlight the need for further research into mechanisms driving long-term long COVID sequelae.

RevDate: 2026-06-12
CmpDate: 2026-06-12

Singer K, Struhal W, S Rabady (2026)

Healthcare Pathways of Patients with Long COVID in Austria: A Qualitative Exploration of Experiences, Barriers, and Needs.

Journal of clinical medicine, 15(11): pii:jcm15114125.

Background/Objectives: Long COVID is characterized by persistent symptoms following SARS-CoV-2 infection and places a considerable burden on patients and healthcare systems due to its complex, multisystemic nature. In Austria, little is known about how affected individuals navigate existing healthcare structures and where obstacles occur. This study aimed to explore healthcare pathways, perceived barriers, and needs among people living with long COVID in Lower Austria. Methods: An exploratory qualitative study was conducted using semi-structured interviews with eleven adults residing in Lower Austria who reported symptoms persisting for at least four months after COVID-19 infection and still present at interview. Participants were recruited from a rehabilitation center, a neurology department, and an online patient group. Interviews were audio-recorded, transcribed verbatim, pseudonymized, and analyzed by the first author using inductive qualitative content analysis following Mayring, supported by MAXQDA 2024 software. Results: On average, each participant consulted five medical points of care and seven healthcare professionals. Approximately half utilized Austria's private healthcare sector in addition to the public one. Key barriers included fragmented care coordination, long waiting times, lack of specialist availability, financial burden, and insufficient recognition of symptoms by healthcare providers. Rehabilitation services were widely perceived as beneficial. Conclusions: Care experiences of the interviewed individuals with long COVID in Austria frequently deviate from national guideline recommendations. Although findings cannot be generalized beyond this exploratory sample, they suggest that enhancing general practitioner (GP) training, reinforcing care coordination, and broadening access to specialized interdisciplinary centers may improve equity and quality of long COVID care.

RevDate: 2026-06-12
CmpDate: 2026-06-12

Renaudineau Y, Teillaud S, Chaves SA, et al (2026)

Clinical and Immunovirological Characteristics Associated with Cardiovascular Dysautonomia in Long COVID.

Journal of clinical medicine, 15(11): pii:jcm15114192.

Background/Objectives: This report is an assessment of the characteristics associated with cardiovascular dysautonomia (CVD) in the context of long Coronavirus disease (COVID), which is currently inadequately characterized. Material and Methods: A retrospective cross-sectional study was performed involving 106 patients with long COVID, including 34 individuals diagnosed with CVD, among whom eight met the criteria for Postural Tachycardia Syndrome (PoTS). The variables assessed encompassed individual characteristics (e.g., age, sex, comorbidities), immunization parameters (e.g., vaccination/viral status, timing, frequency), cellular and humoral anti-Spike and anti-Nucleocapsid (Nuc) immune responses, inflammatory and allergic biomarkers, as well as an extensive panel of common autoantibodies comprising anti-nuclear antibodies, anti-central nervous system antibodies (cerebellum, brain), and anti-peripheral nervous system antibodies (gangliosides). Results: An age < 45 years, body mass index, hyperventilation syndrome as well as a higher cumulative number of antigenic contacts (vaccinations plus infections ≥ 3) and an elevated basophil count (≥0.06 G/L) were independently associated with CVD. There was no association between CVD and inflammatory markers or common autoantibodies. Patients with PoTS criteria had a strong anti-Spike cellular immune response and increased IgG anti-Nuc humoral immunity when compared with CVD and non-CVD long COVID counterparts. Conclusions: Compared to other long COVID patients, patients with long COVID-associated CVD have distinctive clinical and immunovirological features. Our results suggest the potential role of the immune response against Spike and of allergic pathways rather than humoral autoimmunity against common autoantibodies in long COVID CVD.

RevDate: 2026-06-12
CmpDate: 2026-06-12

Balan A, Graham G, Herban S, et al (2026)

Transcutaneous Auricular Vagus Nerve Stimulation for Post-COVID-19 Condition: A Systematic Review and Critical Appraisal of Clinical Evidence.

Journal of clinical medicine, 15(11): pii:jcm15114247.

Background: Long COVID, or post-COVID-19 condition (PCC), affects around 36% of individuals following SARS-CoV-2 infection, manifesting as persistent fatigue, cognitive dysfunction, and dysautonomia among its hallmark features. Affecting an estimated 400 million individuals globally, it imposes an annual economic burden exceeding $1 trillion, yet no pharmacological therapy has demonstrated consistent efficacy in adequately powered randomized controlled trials. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a candidate intervention targeting the autonomic dysfunction and neuroinflammation responsible for PCC pathophysiology. Methods: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420261287286) searching PubMed, Scopus, Cochrane, and Web of Science databases from inception to January 2026 for studies evaluating any form of VNS in adults with Long COVID. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, the JADAD scale, and the PEDro scale. Certainty of evidence was evaluated using the GRADE framework. Narrative synthesis followed SWiM guidelines. Results: Five studies (n = 154 participants) (three randomized controlled trials (RCTs) and two single-arm studies) met inclusion criteria. Three of five studies (60%) were rated high overall risk of bias; only two RCTs achieved "some concerns." The only adequately double-blinded RCT found no significant between-group differences across all outcomes. Paradoxically, in the best-powered RCT (Percin et al.), sham stimulation produced significantly greater fatigue improvement than active taVNS, despite active taVNS producing significant HRV increases consistent with cardiac autonomic modulation. All efficacy outcomes were rated "very low" certainty (GRADE); safety was rated "low" certainty. Conclusions: Currently available evidence supporting the use of taVNS for Long COVID remains limited, and the absence of reliable target engagement markers in the included studies constrains confidence in this approach. Nonetheless, the physiological rationale remains sound, and the favorable safety profile across all included studies supports the feasibility of future investigation. However, given that positive findings were confined to inadequately controlled studies, enthusiasm for further research should be directed first toward mechanistic clarification and rigorous dose-finding work. Large-scale, double-blind, sham-controlled trials incorporating validated markers of vagal engagement are required before taVNS can be firmly recommended for COVID-19 sequelae management.

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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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Collection of publications by R J Robbins

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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Curriculum Vitae for R J Robbins

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