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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 Sep 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: 2026-09-24

Stengel S, N Lindner (2026)

[Diagnosis of Long Covid/Post Covid in Primary Care Settings - Recognition, Classification, and Differentiation].

MMW Fortschritte der Medizin, 168(16):38-41.

RevDate: 2026-09-26
CmpDate: 2026-09-25

Wang CY, Dunnigan JK, Arogundade EO, et al (2026)

Iatrogenic Bilateral Sequential Ocular Sympathetic (Horner Syndrome) Turned Bilateral Parasympathetic Pupil Involvement Associated with Long Coronavirus-Related Dysautonomia: A Case Report.

Case reports in ophthalmology, 17(1):934-941.

INTRODUCTION: This report presents an unusual case of sequential, pharmacologically confirmed iatrogenic bilateral Horner syndrome followed by bilateral Adie's tonic pupil, highlighting the spectrum of ocular dysautonomia associated with long coronavirus disease 2019 (COVID-19).

CASE PRESENTATION: A 41-year-old woman with a history of coronavirus disease 2019 reinfection and multiple comorbidities developed pharmacologically confirmed bilateral Horner syndrome after bilateral stellate ganglion blocks. Subsequent worsening of long COVID-19 symptoms alongside systemic dysautonomia emerged, including postural orthostatic tachycardia syndrome, orthostatic hypotension, and mast cell activation syndrome. The patient then presented with bilateral, poorly reactive, enlarged pupils, and light-near dissociation. Bilateral Adie's tonic pupil was pharmacologically confirmed. Neuroimaging and laboratory workup were unremarkable.

CONCLUSION: As more cases of long COVID-19 emerge, physicians should be aware that long COVID-19 can manifest with rare neuro-ophthalmic presentations, including bilateral pupillary autonomic dysfunction.

RevDate: 2026-09-25

Greco C, S Cross (2026)

Knowing or not knowing: the practical and moral complexity of diagnostic-seeking pathways in situations of medical uncertainty.

Anthropology & medicine [Epub ahead of print].

In this paper, we discuss the practical and moral complexities of diagnostic-seeking pathways for three uncertain medical conditions: fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and long COVID. We analyse qualitative data collected in the UK between 2023 and 2025, comprising in-depth interviews with medical professionals, researchers, and patients, as well as documentary sources. Drawing on the anthropology and sociology of diagnosis, this paper discusses how chronic illness can be marked by challenging and unstable pathways, influenced by the organisation of the medical system and the resources patients have to navigate it. Diagnoses further do not guarantee a solution to the condition, and can, on the other hand, produce stigma. Medical professionals recognise the uncertain nature of these conditions and emphasise how diagnosis can play an instrumental role in providing patients with access to therapies, benefits, or acceptance. Patients discuss the complexity of the strategies they deploy not only to obtain a diagnosis but also to navigate the practical and moral complexities associated with their condition. Analysing the practical and moral complexity of diagnostic-seeking pathways represents a way to enrich anthropological reflections on diagnosis by demonstrating how this key concept of biomedicine is strongly influenced by social, economic, and moral, as well as biological, factors.

RevDate: 2026-09-25

Thomas B, Pattinson R, Cunningham G, et al (2026)

Somatosensory processing in long COVID fatigue and its relations with physiological and psychological factors.

Experimental physiology [Epub ahead of print].

We aimed to quantify somatosensory processing in long COVID and interactions between somatosensory processing, fatigability, fatigue, autonomic function, mood and illness beliefs. Eighty-eight participants (44 long COVID and 44 controls) were invited to complete two testing sessions, where fatigue was induced by either a cognitive or a physical task in a cross-over design; all participants completed at least one session. Baseline questionnaires assessed trait fatigue, autonomic symptoms, mood and illness beliefs. Pre- and post-task measures included somatosensory processing, state fatigue, perceived effort and heart rate variability (HRV). Group differences and task-related changes were analysed using multivariate and linear mixed models. There was no multivariate group effect on baseline somatosensory measures (P = 0.172), nor did they change following exertion or associate with post-exertion fatigue. Long COVID participants reported greater fatigue than controls, with 64% meeting criteria for severe fatigue. State fatigue was greater at baseline, throughout both exertion tasks (all P < 0.001), and increased more during exertion compared with controls. Despite this, cognitive and physical performance changed similarly across tasks, with no group differences in fatigability (P = 0.199-0.441). Long COVID participants had lower resting HRV, indicating autonomic dysfunction, but HRV was not associated with fatigue. Only group status (P < 0.001) and pre-task fatigue (P < 0.001) were associated with post-exertion fatigue. Within long COVID participants, greater depression (P < 0.001) and perceived illness threat (P = 0.033) were associated with greater trait fatigue. The absence of somatosensory abnormalities provides no support for the sensory attenuation model of fatigue in long COVID.

RevDate: 2026-09-26
CmpDate: 2026-09-26

Aladag E, Karakulak UN, IC Haznedaroglu (2026)

Spike Protein at the Crossroads of Long-COVID and Vaccine-Induced Immune Thrombotic Thrombocytopenia Syndromes: A Cardio-Hematological Perspective.

Biomedicines, 14(9): pii:biomedicines14092090.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein is central to viral infectivity, host-pathogen interactions, and immune recognition. Beyond its indispensable role in viral entry, accumulating experimental and clinical evidence indicates that spike protein may exert pleiotropic biological effects involving endothelial, cardiovascular, hematological, neurological, and immunological pathways. During natural infection, these effects occur in the context of active viral replication, additional viral antigens, and systemic inflammation, whereas vaccination induces a fundamentally different, transient exposure to a prefusion-stabilized spike antigen without viral propagation. In this review, we critically examine the molecular and clinicopathological properties of the SARS-CoV-2 spike protein and the biological differences between infection-derived and vaccine-derived spike exposure. Particular emphasis is placed on endothelial dysfunction, platelet and complement activation, immune-thrombosis, persistent viral antigens and tissue reservoirs in Long-COVID, and the distinct anti-PF4-mediated pathophysiology of vaccine-induced immune thrombotic thrombocytopenia (VITT). Emerging evidence suggests that persistent or dysregulated spike-related antigen exposure may contribute to chronic multisystem manifestations in a subset of individuals following SARS-CoV-2 infection; however, evidence linking persistent vaccine-derived spike to chronic clinical syndromes remains substantially more limited and does not currently establish causality. Integrating these observations, we propose the 'Long-Spike' hypothesis as a hypothesis-generating conceptual framework rather than a defined clinical syndrome. Further prospective studies integrating ultrasensitive antigen detection, tissue-based analyses, immunophenotyping, and cardiovascular and hematological biomarkers are required to determine the clinical relevance and causal significance of persistent spike-related antigens.

RevDate: 2026-09-26
CmpDate: 2026-09-26

Hristova M, Massaldjieva R, Atanassova P, et al (2026)

Towards a Neurocognitive Profile of Post-Acute COVID-19: A Longitudinal Study Integrating Subjective Complaints and Computerized Cognitive Testing.

Brain sciences, 16(9): pii:brainsci16090964.

Background/Objectives: The relationship between subjective cognitive complaints and objective performance in post-acute COVID syndrome (PACS), and the persistence of objective impairment over extended follow-up, remain unclear. This prospective longitudinal study characterized the neurocognitive profile of PACS by integrating computerized cognitive testing with structured evaluation of subjective complaints across an extended post-infection interval. Methods: A total of 102 adults with a history of COVID-19 infection (3-35 months post-infection; mean age 40.2 ± 10.95 years; 70.6% female) underwent baseline (V1) CogState Battery testing (seven subtests) and structured assessment of persistent post-COVID complaints; 67 participants (65.7%) constituted the matched longitudinal sample and completed the follow-up (V2) after a mean inter-visit interval of 6.69 ± 1.00 months. Domain-specific composites (Attention/Psychomotor function, Learning/Working memory, and two Global indices) were derived from age-adjusted z-scores, with impairment defined as z ≤ -1.5. Results: Persistent complaints were reported by 63.7% of participants at baseline. In the matched longitudinal sample (n = 67) Attention/Psychomotor impairment was the most prevalent and stable finding in the paired sample (65.7% at V1 and 67.2% at V2; McNemar p = 1.000), whereas ONB-defined working-memory impairment declined nominally in the paired sample (39.4% to 24.2%; p = 0.006), although this change did not remain significant after correction for multiple comparisons (BH-FDR q = 0.063). In the baseline sample persistent complaints were associated with poorer objective performance at V1 across all composite indices with small-to-moderate effect sizes (all BH-FDR-adjusted q = 0.042-0.047). These associations were not observed in the follow-up sample at V2. Age was the most robust demographic correlate of impairment, particularly for visuospatial associative memory (CPAL; β = -0.349, p < 0.001); clinical and demographic predictors explained 9.4-13.9% of the variance (R[2] = 0.094-0.139) in significant models at Visit 1. Conclusions: Attention/psychomotor dysfunction constituted a persistent objective deficit after COVID-19. Subjective complaints at baseline were associated with objective impairments but did not predict cognitive performance at follow-up. These findings support the use of objective computerized cognitive testing alongside symptom screening in the clinical assessment of post-COVID patients. Interpretation is limited by the absence of pre-COVID cognitive data and of a demographically matched healthy, uninfected control group.

RevDate: 2026-09-26
CmpDate: 2026-09-26

Onodera T, Seo S, Sakudo A, et al (2026)

Hyperglycemia in Cats Infected by SARS-CoV-2: Pancreatic Alterations and Potential Antiviral Therapeutics.

Microorganisms, 14(9): pii:microorganisms14091884.

Cats represent a susceptible host and a possible translational model for investigating coronavirus pathogenesis and therapeutics. Recent immunohistochemical (IHC) and histopathological studies in both human and feline tissues have demonstrated SARS-CoV-2 nucleocapsid protein (NP) and spike protein expression within pancreatic islet cells, following a classic temporal infection course. Notably, IHC analysis also reveals NP expression within exocrine ductal epithelial cells. Given that ductal epithelium functions as an islet progenitor pool during tissue injury or metabolic stress, pancreotropic coronaviruses may gain access to the endocrine compartment by exploiting this intrinsic cellular differentiation pathway. Although the precise mechanisms governing intra-islet viral entry remain to be elucidated, this review highlights the capacity of SARS-CoV-2 to compromise both the exocrine (digestive) and endocrine functions of the pancreas. Finally, we evaluate the therapeutic potential of direct-acting antivirals-specifically RNA-dependent RNA polymerase (RdRp) and protease inhibitors-as monotherapies and in synergistic combination to limit pancreatic injury and mitigate the diabetogenic effects of coronaviruses across both acute infection and post-acute sequelae, such as human long-COVID syndrome.

RevDate: 2026-09-26
CmpDate: 2026-09-26

O'Brien S, Butler TJ, Maher E, et al (2026)

Dysautonomia and Postural Orthostatic Syndrome of Hypocapnia in Long COVID Syndrome.

Journal of clinical medicine, 15(18): pii:jcm15186970.

Background: Long COVID syndrome (LCS) affects at least 10% of COVID-19 survivors. Dysautonomia and orthostatic intolerance (OI) are recognised manifestations of long COVID syndrome (LCS). Postural orthostatic syndrome of hypocapnia (POSH) is among the most frequently identified physiological markers of orthostatic intolerance in this patient population. This study aims to evaluate the prevalence of OI and POSH in a cohort of patients with LCS and then treat patients with LCS and evidence of dysfunctional breathing and hypocapnia with targeted respiratory rehabilitation to evaluate the response in physiology and symptoms. Methods: Adults (>18 years) with a diagnosis of long COVID syndrome (LCS) underwent a NASA lean test (NLT) in our dedicated long COVID clinic. The NLT consists of measurements of respiratory rate, heart rate, blood pressure, oxygen saturation, end-tidal carbon dioxide (ETCO2), and symptoms taken over a 10 min period in the supine position, followed by repeated measurements in the leaning position. Patients with evidence of LCS, dysfunctional breathing and hypocapnia from the lean test were referred for targeted respiratory rehabilitation using the Papworth method. Results: A representative sample of patients with LCS (N = 50) underwent the NLT. Orthostatic symptoms were elicited in 50.0% of patients (n = 25) during the NASA Lean Test. Supine or orthostatic hypocapnia was identified in 64.0% of patients (n = 32), while postural orthostatic tachycardia and postural orthostatic hypotension were each observed in 32.0% of patients (n = 16). A total of 62.0% (n = 31) of patients with LCS who had persistent dyspnoea or evidence of OI as supported by supine or orthostatic hypocapnia were referred for targeted respiratory rehabilitation. Of the group referred, 41.9% (13 of the 31) completed respiratory rehabilitation. Comparing mean pre- and post-physiotherapy respiratory rehabilitation values, there was a significant improvement in the Malmö POTS score and the breathing pattern assessment tool (BPAT) (5.7 ± 1.9 vs. 2.1 ± 1.0, p < 0.0001) without a corresponding improvement in end-tidal CO2. Conclusions: These findings provide additional evidence supporting the presence of dysautonomia and OI in patients with long COVID syndrome (LCS). The NLT is a test for OI that can be easily performed in the clinic. Respiratory rehabilitation can improve symptoms related to dysfunctional breathing and OI in LCS. Although hypocapnia has been implicated in orthostatic cerebral vasoconstriction and was postulated as a treatable target in LCS, improvement in the symptoms that we observed were independent of changes in end-tidal CO2 on lean testing.

RevDate: 2026-09-26
CmpDate: 2026-09-26

Bralic M, Silconi FI, Vuletic V, et al (2026)

Neurological Manifestations of Long COVID: Current Evidence, Emerging Concepts, and Future Perspectives.

Journal of clinical medicine, 15(18): pii:jcm15187163.

Six years after the onset of the COVID-19 pandemic, many individuals continue to experience persistent neurological symptoms that extend beyond the acute phase of infection, affecting daily life, work, and overall functioning, thereby representing a substantial long-term health burden. Cognitive impairment, fatigue, headache, and autonomic dysfunction are among the most frequently reported neurological features, often persisting despite the absence of clear diagnostic findings. Although Long COVID is recognized as a distinct clinical entity, the underlying pathophysiological mechanisms remain incompletely understood. This narrative review provides a critical synthesis of current literature regarding the clinical presentations, potential mechanisms, and biomarkers associated with neurological involvement in Long COVID. Reflecting the high heterogeneity of the available evidence, it is important to note that no neurological biomarker or disease-modifying therapy has yet been clinically validated. Ultimately, characterizing these pathways may help define disease heterogeneity, support patient stratification, and guide future personalized therapeutic approaches.

RevDate: 2026-09-26
CmpDate: 2026-09-26

Inaba T, Takagi K, Atsuchi M, et al (2026)

Safety and Changes in Health-Related Quality of Life After Epidural Oxygen Injection for Long COVID/Post-COVID Syndrome: A Multicenter Retrospective Study.

Journal of clinical medicine, 15(18): pii:jcm15187326.

Background/Objectives: Long COVID/post-COVID-19 syndrome is associated with persistent symptoms, including fatigue, headache, and autonomic dysfunction, leading to impaired health-related quality of life (HRQoL). Although epidural oxygen injections have been used in patients with chronic post-traumatic headache and mild traumatic brain injury, their safety and therapeutic effects have not been systematically evaluated. Methods: In this multicenter retrospective study, patients with Long COVID/post-COVID-19 syndrome who underwent their first epidural oxygen injection between April 2022 and December 2025 were included. Safety was assessed by reviewing adverse events. HRQoL was evaluated using the Japanese version of the 36-Item Short-Form Health Survey version 2 (SF-36v2[®]) before treatment and approximately one month afterward. Paired SF-36v2[®] scores were compared using the Wilcoxon signed-rank test with Bonferroni correction. Results: Forty-two patients were included (mean age, 31.9 ± 16.2 years; 21 males). The mean interval between COVID-19 infection and treatment was 16.7 ± 12.8 months. Adverse events occurred in eight patients (subcutaneous emphysema, n = 5; dyspnea, n = 2; back pain, n = 1); they all resolved spontaneously within one week, with no deaths, hospitalizations, or long-term sequelae. Paired SF-36v2[®] data were available for 35 patients. The median scores improved across all domains, with the greatest increase observed in vitality (+25.0 points). All improvements remained significant after Bonferroni correction. Conclusions: Epidural oxygen injection demonstrated a favorable short-term safety profile and was associated with improved HRQoL in patients with Long COVID/post-COVID-19 syndrome. Prospective controlled studies using objective outcome measures are needed to confirm efficacy and clarify the underlying mechanisms.

RevDate: 2026-09-26
CmpDate: 2026-09-26

Song Y, Mehl F, No T, et al (2026)

ACE2-like Catalytic Activity in Anti-SARS-CoV-2 Spike Protein Monoclonal Antibodies.

Pathogens (Basel, Switzerland), 15(9): pii:pathogens15090939.

Many people are affected by difficult-to-understand clinical phenomena associated with acute SARS-CoV-2 infection and by post-acute sequelae of COVID-19 (PASC, or long COVID, LC). The mechanisms responsible for the clinical phenomena have not been well established. The host cell receptor for SARS-CoV-2 is human angiotensin-converting enzyme 2 (ACE2), which binds the SARS-CoV-2 spike protein receptor-binding domain (RBD) to initiate infection. We hypothesized that some people may produce anti-RBD antibodies that sufficiently resemble ACE2 structure to have ACE2-like catalytic activity after infection, and such antibodies are hypothesized to contribute to disease pathogenesis. Our previous studies showed that ACE2-like catalytic activity was associated with immunoglobulin in some acute and convalescent COVID-19 patients. ACE2-like catalytic activity correlated with blood pressure changes following a moderate exercise challenge in people convalescing from COVID-19. To further establish that ACE2-like catalytic activity could be attributed to antibodies, we screened human monoclonal antibodies (mAbs) against SARS-CoV-2 spike protein from three different research centers and others purchased from a commercial source for ACE2-like catalytic activity. We identified four human monoclonal antibodies with ACE2-like catalytic activity. The ACE2-like catalytic activity of these mAbs was not inhibited by MLN-4760, a compound that inhibits native human ACE2 catalytic activity, nor by EDTA, unlike native ACE2, a zinc metalloprotease, but was inhibited by an overlapping pool of spike peptides. Enzyme kinetic studies showed that the mAbs had substantially lower Vmax and Km values than native ACE2, consistent with the characteristics of other catalytic antibodies. The data therefore suggested that the antibodies cleave ACE2 substrate via a mechanism different from native ACE2. The identification of specific mAbs with ACE2-like catalytic activity supports the hypothesis that antibodies induced by SARS-CoV-2 infection could help mediate the pathogenesis of COVID-19 and LC, and, more generally, the hypothesis that catalytic antibodies induced by infectious agents can contribute to disease pathogenesis.

RevDate: 2026-09-24
CmpDate: 2026-09-24

Yu ZN, TC Peng (2026)

COVID-19 Infection and Professional Commitment Among Clinical Nurses: A Cross-Sectional Study of Work Stress and Social Support in Eastern Taiwan.

Nursing reports (Pavia, Italy), 16(9): pii:nursrep16090309.

Background/Objectives: Nurses in Taiwan faced markedly increased nurse-to-patient ratios and a high risk of occupational infection during the COVID-19 pandemic, generating considerable psychological and social strain. Professional commitment-reflecting nurses' identification with, investment in, and intention to remain in the profession-is important for workforce retention and care quality, yet little is known about how contracting COVID-19 affects it. This study examined whether COVID-19 infection and the presence of long COVID symptoms were associated with professional commitment among clinical nurses, and identified sociodemographic, work-stress, and social-support correlates of commitment. Methods: A cross-sectional survey was conducted among registered nurses at a medical center in eastern Taiwan between 21 September 2023 and 28 February 2024. An anonymous electronic questionnaire assessed sociodemographic characteristics, COVID-19 infection/long-COVID status, work stress (Stress Scale for Healthcare Workers Caring for Patients with High-Risk Infectious Diseases), social support (Social Support Scale for clinical nurses), and professional commitment (Hospital Nurses' Job Satisfaction and Professional Commitment Scale). Data from 364 valid responses (response rate 39.8% of the 914 nurses employed at the study hospital) were analyzed using independent-sample t-tests, Pearson correlation, one-way ANOVA, and multiple linear regression. Results: Professional commitment did not differ significantly by COVID-19 infection status (t = 0.50, p = 0.619) or by presence of long COVID symptoms (t = 0.85, p = 0.397). Social support was positively correlated with professional commitment (r = 0.261, p < 0.001), as was work stress, although the latter association was weak (r = 0.116, p = 0.027). Age, job rank, years of service, and education level were significantly associated with commitment (all p < 0.05). Multiple regression indicated that higher social support (B = 0.206, p < 0.001), greater work stress (B = 0.079, p = 0.006), and older age were independently associated with higher professional commitment (R[2] = 0.297). Conclusions: In this cross-sectional sample, COVID-19 infection and long COVID symptoms did not appear to be associated with nurses' professional commitment. Social support, age, and work stress emerged as the correlates most consistently related to commitment, with social support showing the largest association. Given the observational design and the retrospective measurement of work stress and social support, these findings should be regarded as preliminary and hypothesis-generating rather than conclusive. They tentatively indicate that workplace social support may merit further investigation as a potential avenue for sustaining nurses' professional commitment during infectious disease outbreaks.

RevDate: 2026-09-24
CmpDate: 2026-09-24

Del Duca G, Camici M, Sperduti I, et al (2026)

Neurocognitive and Neuropsychiatric Trajectories in a Post-COVID Cohort: A Descriptive Longitudinal Study.

Neurology international, 18(9): pii:neurolint18090163.

INTRODUCTION: Cognitive dysfunction ("brain fog") is a common manifestation of post-acute COVID-19 syndrome (PACS) and may persist long after the acute infection. While cross-sectional studies have described cognitive deficits, longitudinal evidence on recovery trajectories remains limited.

METHODS: We conducted a longitudinal observational study of neurocognitive performance and neuropsychiatric symptoms in patients with PACS. Participants underwent assessment with 20 standardized tests covering five cognitive domains (memory, attention, language, executive functions, psychomotor processing speed); anxiety, depression, and sleep quality were assessed at three time points. Changes were analysed using the Friedman test.

RESULTS: Forty-two patients were included (median age 57 years; 35.7% female) from a predominantly hospitalized cohort (81% hospitalised; 66.7% requiring respiratory support). Patients who completed all three assessments (completers, n = 42) were compared with those who attended the first evaluation but did not complete follow-up (non-completers, n = 544); completers were more severely ill during the acute phase rather than healthier or more motivated. At the group level, statistically significant improvements over time were observed across the whole sample in verbal short-term learning, visuospatial memory, working memory, constructional praxis, phonological verbal fluency, and psychomotor processing speed (all p ≤ 0.05); after Benjamini-Hochberg adjustment across the twenty cognitive outcomes, visuospatial span forward and backward and psychomotor processing speed remained significant (all FDR-adjusted p ≤ 0.013), with the change confined to the first six months. Sleep quality also improved (p < 0.0001).

CONCLUSION: In this cohort, group-level performance improved in six of the twenty tests administered, of which three remained significant after correction for multiple comparisons, while 28 of 42 patients (66.7%) still scored in the impaired range on at least one test at 12 months, and 17 (40.5%) on two or more. These findings highlight the importance of long-term neuropsychological monitoring and integrated cognitive-psychiatric evaluation in post-COVID care. Given the small, predominantly hospitalized sample, improvements should be interpreted cautiously and confirmed in larger controlled studies, although the use of alternate forms for part of the battery makes task-specific learning an incomplete explanation.

RevDate: 2026-09-24

Guinto E, Kuo IC, Chopra S, et al (2026)

Single-cell multi-omics show disruption of blood and airway T cells in pulmonary long COVID.

The European respiratory journal pii:13993003.02001-2025 [Epub ahead of print].

BACKGROUND: Approximately 10% of individuals who recover from COVID-19 experience residual respiratory symptoms impacting their quality of life, but the mechanisms behind pulmonary long COVID (PLC) are largely unknown.

OBJECTIVES: We characterized airway and circulating immune cells in patients with and without PLC.

METHODS: Participants were recruited and allocated into two groups: 1) PLC, defined by a St. George's Respiratory Questionnaire (SGRQ) total score of >10 at least three months following an acute SARS-CoV-2 infection with self-reported new or worsening symptoms, and 2) controls, defined by SGRQ ≤10 with or without a prior history of COVID. We performed research bronchoscopy and obtained bronchoalveolar lavage (BAL) in seven PLC patients and seven age- and sex-matched control subjects. Single-cell RNA sequencing (scRNAseq) was performed on the BAL cells. Peripheral blood mononuclear cells (PBMCs) were cryopreserved in 30 participants (17 PLC, 13 controls) for proteomic analysis. Serum was submitted for microarray detection of auto-IgG antibodies.

RESULTS: We annotated 105 836 cells using scRNAseq and found that CD4[+] T cells were credibly increased in participants with PLC. scRNAseq revealed up-regulation of anti-viral pathways including those related to interferon signaling in T cells as well as antigen presenting cells. In PBMCs, T cells expressing both CD4 and CD8 were elevated in PLC participants. Autoantibodies targeting histone 2B and histone 3 were significantly increased in PLC participants (adj.p<0.05).

CONCLUSIONS: PLC is associated with dysregulation of T cell mediated immunity, which may be related to autoimmunity. These cells represent potential novel therapeutic targets in patients suffering from PLC.

RevDate: 2026-09-24

Sharma S, Rodger EJ, Chatterjee A, et al (2026)

DNA methylation: unifying framework for complex chronic conditions.

Trends in genetics : TIG pii:S0168-9525(26)00221-0 [Epub ahead of print].

Complex chronic conditions represent a growing health burden that is poorly understood and inadequately managed within current health systems. This review focuses on the potential of epigenetic DNA methylation to provide a pathway for better understanding of four closely related conditions: myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID (LC), fibromyalgia (FM), and hypermobile Ehlers-Danlos syndrome (hEDS). These conditions have extensive overlapping symptoms, suggesting shared underlying pathophysiological mechanisms. Epigenetic regulation, particularly DNA methylation, provides a powerful framework for comparative and longitudinal studies across these clinically overlapping conditions. Here, we synthesise evidence from current DNA methylation studies in ME/CFS, LC, and FM, and consider how an integrated cross-condition approach could advance mechanistic insight, enable diagnostic stratification, and improve patient outcomes.

RevDate: 2026-09-24
CmpDate: 2026-09-23

Humer B, Eyisoylu H, Berentschot JC, et al (2026)

A brief report: absence of elevated circulating NETosis markers in long-term long COVID.

Frontiers in cellular and infection microbiology, 16:1920533.

BACKGROUND: Neutrophil extracellular trap (NET) formation (NETosis) has been proposed as a contributor to the pathophysiology of Long COVID (LC). However, it remains unclear whether markers of systemic NETosis remain elevated in individuals with persistent symptoms years after the initial infection.

METHODS: To assess NETosis, we quantified MPO-DNA, Histone DNA, and Citrullinated H3 levels in the plasma of 51 patients with prolonged LC (mean disease duration of three years), and compared them with 52 age- and sex-matched healthy controls.

RESULTS: No significant differences were observed between participants with LC and healthy controls for any of the three NETosis markers. Hierarchical clustering reveals no specific subgroups in the patient group. Furthermore, NETosis marker levels were not associated with overall symptom burden or individual symptom domains.

CONCLUSIONS: In this cohort of individuals with long-term LC, we found no evidence of persistent systemic NETosis. These findings suggest that elevated circulating NETosis markers are not a universal feature of long-term LC and may indicate that neutrophil activation observed during acute or early post-acute disease does not persist in long-term disease.

RevDate: 2026-09-24
CmpDate: 2026-09-23

Liu T, Ashok D, Pekosz A, et al (2026)

Dynamic changes in cardiac autonomic function persist in the postacute phase after SARS-CoV-2 infection in a hamster model of COVID-19.

Heart rhythm O2, 7(9):1746-1761.

BACKGROUND: Autonomic nervous system (ANS) dysfunction is a central feature of long coronavirus disease syndrome, yet little is known about how it develops during and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

OBJECTIVE: This study aimed to characterize the time course of dynamic changes in linear and nonlinear heart rate variability measurements as indices of ANS function for up to 2 months after infection.

METHODS: Hamsters implanted with radiotelemetry devices were inoculated with SARS-CoV-2. Electrocardiograms and subpleural pressures were recorded before infection, and for 56 days postinfection (DPI). Heart rate variability and respiratory sinus arrhythmia were analyzed and compared with the preinfection baseline or mock-infected controls. Ruxolitinib or mitochondrially targeted 2,2,6,6-tetramethylpiperidine-1-oxyl was administered from 4 days before infection to 10 DPI to assess the effects of Jak/Stat inhibition or antioxidant treatment, respectively.

RESULTS: ANS activity follows 3 phases after infection: (1) a pronounced increase in parasympathetic activity relative to sympathetic activity during the acute phase of infection (1-4 DPI), (2) a decrease in overall ANS activity in the subacute phase (7-14 DPI), and (3) re-emergence of elevated sympathetic and parasympathetic inputs that continue to increase during the postacute phase (28-56 DPI). The conclusions are corroborated by changes in respiratory sinus arrhythmia analysis and acute pharmacologic inhibition of cholinergic and β-adrenergic signaling. Postacute ANS remodeling was suppressed by early inhibition of innate immune signaling or mitochondrial oxidative stress.

CONCLUSION: Cardiac dysautonomia after SARS-CoV-2 infection is phase dependent. Inhibiting early immune activation or mitochondrial oxidative stress during the acute phase offers a strategy to suppress postacute ANS remodeling that could contribute to long coronavirus disease syndrome.

RevDate: 2026-09-23

Angus DC, MB O'Connor (2026)

Long COVID: The Problem Society Wants to Forget: A Healthy Dialogue With E. Wesley Ely.

JAMA pii:2854450 [Epub ahead of print].

RevDate: 2026-09-23
CmpDate: 2026-09-23

Rubilar P, Apablaza M, Ramírez-Santana M, et al (2026)

Post-COVID symptoms prevalence, latent class pattern, and functional impact: A population-based cross-sectional study in two Chilean cities, 2024.

Medwave, 26(8):e3234.

INTRODUCTION: Post-COVID-19 condition affects approximately 6% of individuals globally. Most evidence is based on hospitalized patients and is from countries with relatively low vaccination coverage. This study estimates the prevalence of symptoms compatible with post-COVID-19 and explores symptom patterns in a population-based sample from Chile, a country with high vaccination coverage. Moreover, it examines their associations with daily activities and demographic, social, and clinical factors.

METHODS: A cross-sectional study was conducted in May 2024 in two Chilean Cities, involving 654 participants (88.5% response rate) aged ≥ seven years, from randomly selected households. Ten post-COVID-19 symptoms that persisted for ≥ three months were collected. Latent class analysis identified symptom patterns.

RESULTS: Among 277 participants with a confirmed COVID-19 diagnosis, 114 reported at least one symptom lasting ≥ 3 months. Population-weighted prevalence of at least one post-COVID-19 symptom was 17.4% in the general population and 40.7% among individuals with prior COVID-19. Among those with post-COVID-19 symptoms, 40.1% reported a reduction in daily activities. Three classes were explored: class 1 (38.4%) characterized by fatigue, ageusia/anosmia, and muscular/joint pain; class 2 (40.7%) with predominant cardiorespiratory symptoms; and class 3 (20.9%) with multisystemic symptoms. Class three was associated with a higher frequency of comorbidities (particularly diabetes), hospitalization, multiple COVID-19 episodes, and Aboriginal affiliation. Classes 2 and 3 were independently associated with younger age and diabetes, class 2 was additionally associated with lower educational attainment and lower BMI, while class 3 was additionally associated with Aboriginal affiliation.

CONCLUSIONS: This population-based study reveals a substantial burden of at least one post-COVID-19 symptom, with distinct symptom classes highlighting the need for tailored interventions. These findings underscore the importance of targeted public health policies and personalized clinical approaches, particularly for severe symptom classes that impact quality of life and contribute critical data from Latin America to the global understanding of post-COVID-19 condition.

RevDate: 2026-09-23
CmpDate: 2026-09-24

Haojing Z, Lin K, P Dianzhu (2026)

Building and externally validating a prediction model for long COVID in severe and critical COVID-19 patients: a multi-center cohort study.

BMC pulmonary medicine, 26(1):.

OBJECTIVE: To explore the risk factors of Long COVID and to construct a nomogram to predict the occurrence of Long COVID.

METHOD: This study was an observational study. Clinical data were collected from patients diagnosed with COVID-19 and hospitalized at the First Affiliated Hospital of Jinzhou Medical University Hospital from December 7, 2022, to February 1, 2023. The prediction model was constructed using a nomogram. The clinical data of patients in Panjin Central Hospital Hospital from December 7, 2022 to December 7, 2023 were used for external validation.

RESULTS: In the development cohort and the validation cohort of this study, 60.3% and 62.3% of the patients developed Long COVID, respectively. After Least absolute shrinkage and selection operator regression, the final variables included in the prediction model were percentage of lymphocyte, the Charlson Comorbidity Index, Computed Tomography score, and oxygen requirement. The Area Under the Receiver Operating Characteristic for external validation of the model is 0.786, and the p value of Spiegelhalter test was 0.126. The p value of the Hosmer and Lemeshow chi-square statistic was 0.098. The decision curve analysis indicates that the model performs well.

CONCLUSION: The prediction model developed in this study is useful for assessing the likelihood of developing Long COVID in hospitalized patients.

RevDate: 2026-09-24

Theoharides TC, P Papadopoulou (2026)

Correction: Pathogen effects on the brain: the case of SARS-CoV-2 spike protein and neuro COVID.

Frontiers in neurology, 17:1945736.

[This corrects the article DOI: 10.3389/fneur.2026.1853951.].

RevDate: 2026-09-24
CmpDate: 2026-09-24

Filip P, Bartečková E, Hořínková J, et al (2026)

Latent brain-cognition dimension indicative of neuroinflammatory basis of Long COVID.

Brain communications, 8(5):fcag344 pii:fcag344.

Long COVID is characterized by persistent multisystemic symptoms with poorly defined pathophysiological substrate. The presented study investigated whether Long COVID is associated with alterations in brain microstructure and cognition by jointly modelling multimodal MRI and neuropsychological data within a shared framework. One hundred nine participants (77 Long COVID, 32 controls) without the history of severe acute COVID infection underwent quantitative MRI (T1, T2, T1ρ, T2ρ relaxometry, neurite orientation dispersion and density indices derived from diffusion-weighted imaging) and neuropsychological testing. The resulting brain-cognition axis provided a robust group separation across dimensionalities (permutation P ≈ 0.02), with 72.6% of variance attributable to cognition and 27.4% to MRI features. The predominant imaging features included higher isotropic free-water and reduced neurite density, with minimal relaxometry influence. Projection of discriminant weights back to anatomy revealed involvement over cortico-subcortical dorsal attention, salience and limbic circuits, consistent with patients' cognitive complaints. Furthermore, brain-cognition axis score correlated not only with the global Long COVID symptom burden but also with its respiratory, systemic, and neurological domains without clear predominance for any symptom group (partial R [2] ≈ 0.10-0.18, q < 0.01). Hence, although the cognitive profile provided the dominant discriminative anchor in group separation, neuroimaging offered complementary information and pathophysiological background for the clinically apparent cognitive phenotype. The prominence of neuroinflammation-sensitive MRI protocols highlights probable immune and vascular contributions rather than overt neurodegeneration as the basis of Long COVID in individuals without a severe acute infection course.

RevDate: 2026-09-24
CmpDate: 2026-09-24

Axon DR, S Fenwick (2026)

Investigating the Variables Associated with Having a Functional Limitation Among Adults with Long COVID: A Cross-Sectional Database Study Using the United States Medical Expenditure Panel Survey.

Diseases (Basel, Switzerland), 14(9): pii:diseases14090339.

BACKGROUND/OBJECTIVES: Functional limitations are one of many potential clinical consequences for people living with long COVID. However, medical, health, and demographic variables associated with functional limitations in this population have not been fully characterized. The objective of this study was to identify variables associated with having a functional limitation among United States (US) adults with long COVID in a nationally representative dataset.

METHODS: This was a cross-sectional analysis of US adults in the 2023 Medical Expenditure Panel Survey (MEPS). A multivariable logistic regression model was created to identify factors associated with reporting functional limitations versus no functional limitations in people with MEPS-defined long COVID.

RESULTS: In this study, 26% of adults with MEPS-defined long COVID reported functional limitations. Factors that were associated with functional limitations in people with long COVID included non-married status versus married (odds ratio [OR] = 1.8), having 2-4 chronic health conditions versus 0-1 conditions (OR = 2.8), being unemployed versus employed (OR = 3.5), having public health insurance versus uninsured (OR = 5.3), and reporting pain interference versus no pain (little pain interference, OR = 2.3; moderate interference, OR = 8.8; extreme/quite a bit of interference, OR = 16.9). No other associations were found.

CONCLUSIONS: Functional limitations are common in people experiencing long COVID. Several factors were associated with functional limitations in this population of individuals with long COVID, although whether the functional limitation was caused by long COVID or another problem was unknown. Further research is needed to better understand factors associated with long COVID and to explore the scope and severity of functional limitations in long COVID.

RevDate: 2026-09-24
CmpDate: 2026-09-24

Ignacio Albino M, Hernández Ortega Y, Chaparro Díaz L, et al (2026)

Clinical Manifestations Associated with Pain in Nursing Students in Emerging Adulthood with Long COVID.

Nursing reports (Pavia, Italy), 16(9): pii:nursrep16090302.

Objective: To identify the clinical manifestations associated with pain in nursing students in emerging adulthood with Long COVID (LC). Methods: A cross-sectional, descriptive, and analytical study was conducted. The universe comprised 1508 students from a Faculty of Nursing in the State of Mexico. The sample size of 307 participants was calculated using Cochran's formula (1977) with 95% confidence and a 5% margin of error, with correction for finite populations; participants were invited through an open call and selected non-probabilistically according to inclusion criteria and willingness to participate. Instrument: A questionnaire on post-SARS-CoV-2 health conditions was used, with reliability assessed in a pilot test through internal consistency measures, obtaining a Cronbach's Alpha = 0.86 and KR-20 = 0.87. It was administered between the third and fourth week following the three-month mark after COVID-19 onset. Descriptive analysis, Fisher's exact test, and a binary logistic regression model were used, with pain as the dependent variable (1 = yes, 0 = no); statistical significance was set at p < 0.05, with a 95% CI. Results: 40.4% of students reported pain-(46.6%) males and (39.0%) females-with a significant association between age group and pain (p < 0.001). A total of 198 painful clinical manifestations were reported: headache (48.0%), chest oppression (26.8%), and myalgias (23.2%). The model showed that taste alteration (p < 0.001) and decreased vision (p < 0.001) were associated with a lower likelihood of pain, while gastrointestinal alterations (p = 0.025) and fatigue (p = 0.048) were associated with a higher likelihood of pain. Conclusions: Pain in students with LC is associated with clinical manifestations, mainly gastrointestinal alterations, and fatigue.

RevDate: 2026-09-23
CmpDate: 2026-09-22

Reeves J, SWM Cheng (2026)

Accurately synthesising evidence for long COVID rehabilitation.

ERJ open research, 12(5):.

New correspondence: reflections on a recent systematic review of rehabilitation for long COVID https://bit.ly/4wMsD7y.

RevDate: 2026-09-23
CmpDate: 2026-09-22

Chakraverty S, Maru N, Megaritis D, et al (2026)

Reply to: Accurately synthesising evidence for long COVID rehabilitation.

ERJ open research, 12(5):.

Methodological flexibility is often required in evolving evidence bases, but must be accompanied by clear, transparent reporting to preserve scientific rigour https://bit.ly/4v60M0I.

RevDate: 2026-09-22
CmpDate: 2026-09-22

Khawandi J, Patel K, Azzam M, et al (2026)

The role of 6-minute walk test and pulmonary function testing in patients with post COVID-19 condition: a systematic review and meta-analysis.

Family practice, 43(5):.

BACKGROUND AND OBJECTIVE: Post-COVID-19 condition (PCC) is a complication of acute COVID-19 infection, which often presents with respiratory symptoms. This review aimed to assess the prevalence of abnormal pulmonary function test (PFTs) and 6-minute walk test (6MWT) with oximetry findings, and their respective prevalence and magnitude of abnormalities in patients 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 30 studies that reported on the prevalence of abnormal PFTs and/or 6MWT in patients with PCC. Outcomes within PFTs and 6MWT showed that patients with PCC have a higher probability of having abnormal tests, with those hospitalized during their acute COVID-19 infection showing a higher probability of having abnormal tests. The overall certainty of the evidence was very low due to the high risk of bias, indirectness, and imprecision.

CONCLUSION: This review provides insight into the utilization of PFTs and 6MWT and the frequency of test abnormalities in patients with PCC. Despite existing evidence, there is a need for future studies to assess the diagnostic test accuracy of these tests in PCC.

RevDate: 2026-09-22

Zhang L, Cui J, Saleem M, et al (2026)

Post-infection increases in Cardiometabolic Disease Staging (CMDS) scores are associated with increased odds of long COVID in a longitudinal retrospective cohort.

Diabetes research and clinical practice pii:S0168-8227(26)00498-5 [Epub ahead of print].

AIMS: We applied a validated Cardiometabolic Disease Staging (CMDS) model, which quantitatively measures CMD severity, to assess whether changes in cardiometabolic risk surrounding COVID-19 infection were associated with the risk of developing Long COVID.

METHODS: CMDS scores (range 0.01 - 0.99) were calculated using body mass index, glucose, blood pressure, cholesterol, and triglycerides, collected up to three years before and after COVID-19 infection. Long COVID was defined using ICD-10 codes or self-reported symptom interference. Changes in CMDS scores and the odds of Long COVID were examined using logistic regression.

RESULTS: A total of 6,364 patients [mean age: 57 years (SD 15); 58% female; 67.1% White] had available clinical data and Long COVID outcomes; 6.9% met criteria for Long COVID. Patients with Long COVID had significantly higher CMDS scores than those without Long COVID both before (0.21 vs. 0.19; p = 0.013) and after (0.24 vs. 0.19; p < 0.0001) COVID infection. Those whose CMDS score increased after COVID-19 infection had a 1.36-fold (OR 1.36; 95% CI: 1.08-1.71) increased odds of having Long COVID, remaining significant after adjusting for SDoH and comorbidities.

CONCLUSIONS: Patients who increased in cardiometabolic disease severity after COVID-19 infection had increased odds of developing Long COVID.

RevDate: 2026-09-19
CmpDate: 2026-09-18

Baik SH, Xian H, Baye F, et al (2026)

Deep learning survival analysis with time-varying covariates: extending PyCox to assess COVID-19 antiviral treatments and long-COVID associations.

JAMIA open, 9(5):ooag186.

OBJECTIVES: To extend the PyCox to accommodate time-varying covariates using counting process data, addressing immortal time bias in survival analysis.

MATERIALS AND METHODS: We modified PyCox to support counting process data structures for time-varying covariates and applied it to 2 246 913 Medicare beneficiaries aged ≥65 with COVID-19 (January-September 2022; 2 785 807 longitudinal records). We compared traditional Cox regression, original PyCox, and modified PyCox in estimating associations between early antiviral treatment (nirmatrelvir or molnupiravir) and long-COVID. Performance metrics included concordance index (C-index), integrated Brier score (IBS), and integrated negative binomial log-likelihood (IBLL) and time-dependent Area Under the Receiver Operating Characteristic Curve (AUC), Brier score, and permutation importance.

RESULTS: Among patients, 19.5% received nirmatrelvir, 2.6% received molnupiravir, and 14% developed long-COVID. Traditional Cox and modified PyCox produced concordant hazard ratios (HR) for nirmatrelvir (0.874 and 0.878) and molnupiravir (0.909 and 0.918); original PyCox estimated stronger associations (HR = 0.822 and 0.879). The treatment-effect difference formed a gradient: 3.5-4.0 percentage-points for time-varying models, 4.6 for time-fixed Cox, and 5.7 for time-fixed PyCox. Discrimination, calibration, and fit were comparable overall; modified PyCox showed higher time-dependent AUCs (0.536-0.609) than time-fixed PyCox (0.481-0.519) and relied on largely different top predictors. Modified and original PyCox trained in 1 min 14 s and 3 min 18 s, vs 5 min for traditional Cox.

DISCUSSION: Treatment-contrast magnitude and covariate importance varied by models, suggesting temporal covariate structure and modeling approach jointly influence treatment-effect estimates.

CONCLUSION: Extending PyCox to accommodate time-varying covariates improves computational efficiency while maintaining estimation accuracy comparable to standard time-varying methods.

RevDate: 2026-09-19
CmpDate: 2026-09-18

Varga B, Martinez-Archundia M, Willemsen LEM, et al (2026)

A systems microbiology framework for reproducible multi-dataset omics integration with application to long COVID.

Frontiers in systems biology, 6:1873899.

Integrative systems microbiology increasingly relies on algorithmic approaches capable of extracting biologically meaningful patterns from heterogeneous and often high dimensional, low-sample-size (HDLSS) biological datasets. A major obstacle in this setting is the instability of inferred molecular signatures across cohorts, tissues, and measurement platforms. Here, we address this problem by formulating molecular system inference as a multi-dataset integration task and by applying the Matthews Correlation Coefficient-Recursive Ensemble Feature Selection (MCC-REFS) algorithm to jointly analyze five independent transcriptomic datasets spanning peripheral blood mononuclear cells, whole blood, plasma, and post-mortem tissues. We compared MCC-REFS with three commonly used feature-selection strategies, GRACES, SelectKBest, and Deep Neural Pursuit (DNP), in order to evaluate robustness, convergence, and cross-context reproducibility. MCC-REFS consistently converged on a compact seven-gene system (PPP2CB, SOCS3, ARG1, IL6R, ECHS1, FZD2, TRGV3/5) exhibiting higher stability indices and stronger classification performance than alternative methods. Generalization was assessed using an independent multi-layer perceptron classifier across validation cohorts with differing tissue origin and sequencing technologies, demonstrating preservation of discriminative structure. To support interpretation, we integrated functional, pharmacological, and interventional knowledge from DrugBank, DGIdb, and Open Targets, enabling the mapping of inferred gene systems onto pathways, known drug targets, and ongoing clinical investigations. Taken together, this work presents an algorithmic framework for multi-dataset and multi-omics integration in systems microbiology, illustrating how stable and interpretable molecular patterns can be identified from heterogeneous data, with Long COVID serving as a representative case study.

RevDate: 2026-09-21

Zhang SS, Wang H, Yang YS, et al (2026)

Olfactory Tuft Cells Are Critical to Basal Inflammation, Innate Immune Response to Viral Infection, and Modulation of Quiescent Stem Cell Activation, Proliferation and Differentiation.

Cell proliferation [Epub ahead of print].

The olfactory mucosa serves as both a sensory organ and an immune barrier to protect against bacterial and viral invasion and other insults. It is unclear how different types of olfactory mucosal cells coordinate and contribute to these two functions. We set out to reveal the critical roles of a subset of microvillous cells of the mucosa, olfactory tuft cells, in protecting and reconstructing this vital olfactory sensory organ. We first validated the expression of canonical gustatory signalling proteins and other molecular markers in olfactory tuft cells. Genetic disruption of the Gng13 and Trpm5 genes that encode the two gustatory signalling proteins, G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, resulted in elevated basal inflammation and enhanced activation of the quiescent stem cells-horizontal basal cells (HBCs) in the mucosa. Nasal infection of H1N1 influenza virus further exacerbated the inflammation and delayed the resolution of inflammation in the mutant mucosa, including more immune cell infiltration, augmented cytokine production and cell death, increased HBC proliferation and direct differentiation into tuft cells, and prolonged olfactory tuft cell hyperplasia. Cytokine treatment of the cultured olfactory epithelial organoids indicated that the cytokines that were found to be elevated in the mutant mucosa, including interleukin-4 (IL-4), IL-13 and interferon-γ (INF-γ), are able to stimulate HBC activation. Together, our results indicate that olfactory tuft cells play an important role in maintaining the baseline inflammation under the steady-state condition, and altering inflammatory magnitude and modulating HBC activation and differentiation in the olfactory mucosa following the viral infection. Our findings shed light on new roles of olfactory tuft cells in innate immune response, quiescent stem cell activation and neuroimmune interactions, and provide novel therapeutic targets for preventing and treating stem cell-related olfactory disorders such as chronic rhinosinusitis and long COVID.

RevDate: 2026-09-21

Kontowicz E, Irish AK, Lee LC, et al (2026)

Characteristics Associated With Persistent Long COVID Symptoms in Healthcare Personnel Infected With SARS-CoV-2 Between August 2022 and May 2024: A Multicenter Cohort Analysis of US Healthcare Personnel.

American journal of industrial medicine [Epub ahead of print].

BACKGROUND: Long COVID affects a significant proportion of COVID-19 survivors. This study examined persistent Long COVID symptoms among healthcare personnel (HCP) and evaluated associations with vaccination, prior SARS-CoV-2 infection, underlying health conditions, and demographics.

METHODS: COVID-19-positive HCP were identified from a multi-state study of COVID-19 vaccine effectiveness. Electronic surveys collected symptom data at 3- and 6-month post-infection. The primary outcome, persistent Long COVID symptoms, was defined as the same moderate or severe symptom reported at both timepoints. Multivariable logistic regression estimated adjusted odds ratios (aOR) for persistent Long COVID, adjusting for demographics, recent vaccination, prior infection, and acute-phase illness severity.

RESULTS: Overall, 11.3% (169/1496) of HCP reported persistent Long COVID symptoms. Older age was associated with higher odds of persistent symptoms when compared to HCP ages 18-29 years: for ages 50-64 years, aOR = 1.94, 95% CI 1.09-3.49 and ≥ 65 years, aOR = 3.52, 95% CI 1.50-8.25. Female HCP had greater odds for persistent Long COVID (aOR = 3.05, 95% CI 1.58-5.86) than males. Prior infection (aOR = 1.78, 95% CI 1.14-2.78) and ≥ 2 underlying health conditions (aOR = 2.49, 95% CI 1.66-3.73) were associated with higher odds. Conversely, physicians (aOR = 0.21, 95% CI: 0.05-0.91), licensed practical and registered nurses (aOR = 0.59, 95% CI: 0.37-0.94), and therapists or therapist assistants (aOR = 0.27, 95% CI: 0.09-0.77) had lower odds versus non-clinical HCP.

CONCLUSION: These findings underscore the frequency of persistent Long COVID symptoms among HCP and their potential to strain the healthcare workforce.

RevDate: 2026-09-22
CmpDate: 2026-09-22

Cao C, Chen S, Liu Y, et al (2026)

Long-term impact of COVID-19 on haemophilia: a multicenter study in Southwest China.

BMC infectious diseases, 26(1):.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is not yet over as millions of people are still diagnosed with persistent symptoms of COVID-19 (long COVID) worldwide. Despite some advances in haemophilia research, the precise relationship between COVID-19 and haemophilia remains elusive, warranting further investigation.

METHODS: A total of 254 cases of people with haemophilia (PwH) infected with COVID-19 from Southwest China were enrolled in the present study. Baseline characteristics, clinical manifestations, treatment methods, and vaccination data were collected and analyzed. Patients were followed up for clinical characteristics at 1, 2, 4, and 16 weeks and 6 months after COVID-19. The spontaneous bleeding characteristics, joint functional status (assessed by the Haemophilia Joint Health Score [HJHS] and Haemophilic Early Arthropathy Detection with Ultrasound [HEAD-US]), coagulation factor inhibitors formation, characteristics of long COVID and changes in mental state were analyzed.

RESULTS: The clinical features of the 254 PwH were analyzed in the study. A significant reduction in spontaneous bleeding frequency was observed in all body regions except the gingiva during COVID-19 (p < 0.05). This pattern of reduced bleeding during infection, followed by an increase post-infection, was observed across the cohort, which included patients with varying severities of haemophilia (severe, n = 167; moderate, n = 59; mild, n = 28). In addition, PwH developed long COVID, characterized by chronic cough (7.87%) and fatigue (5.12%). Six months after COVID-19 infection, approximately 13.39% of PwH showed anxiety and the number of patients with moderate depression and extremely severe depression increased significantly (p < 0.05). During the six-month follow-up, no significant alterations in coagulation factor activity or joint functional status were observed among PwH. A comparison of joint functional status before and after COVID-19 infection revealed no significant difference in the HJHS, with scores of 21.79 ± 15.79 vs 23.81 ± 14.96 (p > 0.05). The HEAD-US Score was 20.33 ± 11.93 vs 20.62 ± 12.61, p > 0.05. In addition, one patient developed coagulation factor Ⅷ inhibitors after COVID-19 infection.

CONCLUSIONS: This study indicates that spontaneous bleeding episodes are decreased among PwH during COVID-19 infection, and the infection does not cause deterioration of joint function. In addition, it underscores the necessity of close monitoring of long COVID-related impacts as well as COVID-19-associated mental health conditions in PwH.

CLINICAL TRIAL NUMBER: Not applicable.

RevDate: 2026-09-20

Tsiodras S (2026)

Post-influenza syndromes: a hidden burden in clinical practice.

Expert review of respiratory medicine [Epub ahead of print].

INTRODUCTION: Influenza is still taught and managed as a self-limited acute respiratory illness. The COVID-19 pandemic forced a reexamination of every respiratory virus and made a longer time horizon impossible to ignore. Comparator-controlled cohort data now indicate that influenza, like SARS-CoV-2, is followed by persistent, new-onset multi-system disease that is largely invisible in practice.

AREAS COVERED: This perspective reframes influenza as a systemic infection with a distinct post-acute footprint. Drawing on autopsy, experimental and comparative-cohort evidence, a working construct of post-acute influenza syndrome (PAIS) is outlined across its cardiovascular, pulmonary, infectious, neurological, metabolic, renal and immunological components. Literature was identified through PubMed searches combining post-acute, post-influenza and post-viral terms with influenza (run to June 2026), with citation tracking, prioritizing studies with a non-influenza comparator. Influenza is framed as a cardiovascular stress test and a trigger of long-term multimorbidity in the already vulnerable, alongside the unresolved conflict over whether its cardiac burden exceeds that of COVID-19.

EXPERT OPINION: Post-influenza sequelae are real, clinically consequential, and systematically missed because of delayed onset, attribution bias and fragmented care. Vaccination, longitudinal follow-up of high-risk survivors and integrated care pathways should become standard practice within five years.

RevDate: 2026-09-17

Orzeł U, Wójcik E, Filipek S, et al (2026)

ACE2 dysregulation and lipid metabolism: Mechanistic interplay between COVID-19 and neurodegeneration.

Molecular aspects of medicine, 112:101519 pii:S0098-2997(26)00075-0 [Epub ahead of print].

Angiotensin-converting enzyme 2 (ACE2) is the primary cellular receptor of SARS-CoV-2. It is a key regulator of the renin-angiotensin system (RAS) and modulates blood pressure and inflammatory pathways. ACE2 converts pro-inflammatory angiotensin II into the vasoprotective peptide, angiotensin (1-7). This is strongly influenced by the lipid composition of the plasma membrane. Cholesterol-rich lipid rafts play an important role in determining receptor localisation and viral accessibility. Dyslipidaemia, which is common in obesity, diabetes, and metabolic syndrome, has been associated with an increased susceptibility to severe COVID-19 and may amplify systemic inflammation. Aberrant lipid metabolism also contributes to neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, which drive neuroinflammation, synaptic dysfunction, and blood-brain barrier impairment. Notably, similar disturbances and systemic inflammation are increasingly recognised in patients with Long COVID, suggesting overlapping mechanisms that may exacerbate or accelerate neurodegenerative processes. This review explores the interplay between ACE2 regulation, lipid metabolism, and systemic inflammation in COVID-19, with a particular focus on their implications for neurological health. Uniquely, we highlighted the intersection of ACE2 and lipid-related alterations in patients with Long COVID and their potential contribution to the progression of neurodegenerative diseases. In addition, we reviewed therapeutic strategies targeting ACE2, including recombinant soluble ACE2, ACE2-based nanotherapeutics, and lipid-focused interventions, aimed at mitigating acute infection, systemic inflammation, and persistent neurological sequelae. Understanding these mechanisms is essential to prevent long-term neurological consequences of the COVID-19 pandemic.

RevDate: 2026-09-16

Huang Z, Se Soh AM, Zeng K, et al (2026)

Associations of age, COVID-19 vaccination, and SARS-CoV-2 infection history with health-related quality of life in a community-based longitudinal cohort in Singapore.

Journal of infection and public health, 19(10):103359 pii:S1876-0341(26)00231-5 [Epub ahead of print].

OBJECTIVES: To assess associations between COVID-19 infection, Long COVID, and health-related quality of life (HR-QoL) in a prospective community serological cohort in Singapore.

METHODS: Participants with mild or no infection were followed over 30 months (from August 2020). HR-QoL was measured using the SF-36 at visits 5 and 6 (December 2022-September 2023). Mixed-effects linear regression models examined associations between infection status and SF-36 domains, adjusting for sociodemographic and clinical factors, with age-time since infection interactions.

RESULTS: Among 1106 participants (aged 16-94 years), COVID-19 infection was associated with lower HR-QoL, with associations differing by age and time since infection. Participants aged ≥ 65 years had lower physical and mental HR-QoL, including beyond one-year post-infection. Among participants aged 16-64 years, lower HR-QoL was observed during the first 45 days after infection. Long COVID symptoms were associated with lower HR-QoL across multiple domains. Receipt of ≥ 3 mRNA vaccine doses was associated with higher physical and mental HR-QoL scores.

CONCLUSIONS: Post-COVID HR-QoL differed substantially by age. Older adults had lower HR-QoL across multiple domains, whereas younger participants showed lower HR-QoL primarily during the early post-infection period. Vaccination and the absence of Long COVID were associated with better HR-QoL outcomes.

RevDate: 2026-09-16

Lemogne C (2026)

CBT-informed care for long COVID: Current evidence and priorities for future research.

RevDate: 2026-09-18
CmpDate: 2026-09-17

Zarbatan FA, Alawam K, A Hakamy (2026)

Pulmonary sequelae of SARS-CoV-2 infection: a narrative review of long-term functional, radiological, and clinical outcomes in COVID-19 survivors, with a regional focus on Saudi Arabia.

Frontiers in physiology, 17:1916914.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has left an enduring legacy of pulmonary morbidity among millions of survivors worldwide. While the acute phase of COVID-19 has been extensively characterized, the long-term pulmonary sequelae collectively termed post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID remain incompletely understood, particularly across diverse geographic and demographic populations. This narrative review synthesizes current evidence on the long-term pulmonary consequences of SARS-CoV-2 infection, with emphasis on functional, radiological, and clinical outcomes in survivors. Literature was identified through systematic searches of PubMed, Scopus, and Google Scholar covering publications from January 2020 to September 2025, using pre-specified search terms related to long COVID pulmonary outcome; studies involving adult survivors with objectively assessed pulmonary outcomes were prioritized. This review addresses the pathophysiological mechanisms underlying pulmonary injury, the definition and clinical spectrum of long COVID, the trajectory of pulmonary function test (PFT) abnormalities-particularly reductions in diffusing capacity for carbon monoxide (DLCO) and radiological findings detected on high-resolution computed tomography (HRCT). Risk factors for persistent pulmonary dysfunction, the impact on health-related quality of life (HRQoL) and functional capacity, emerging evidence supporting structured pulmonary rehabilitation, and the specific context of Saudi Arabia and the Jizan region are also examined. A particular focus on the Arabian Peninsula is warranted given that regional populations carry a high burden of metabolic comorbidities including obesity, diabetes mellitus, and hypertension that may amplify pulmonary vulnerability to SARS-CoV-2 yet remain substantially underrepresented in the current literature. The available evidence suggests that impaired gas exchange most consistently reflected by reduced DLCO may represent the most prevalent long-term pulmonary consequence of COVID-19, with restrictive ventilatory patterns predominating over obstructive defects. Significant gaps persist regarding the long-term trajectory of these abnormalities, population-specific risk stratification, and the efficacy of targeted rehabilitation. Structured, longitudinal, multicenter research incorporating standardized PFT protocols is urgently needed to address these unresolved questions and guide evidence-based post-COVID pulmonary care.

RevDate: 2026-09-15

Marsiglia MD, Rovito R, Amendola A, et al (2026)

Beyond seropositivity: SARS-CoV-2 IgG responses in high-risk COVID-19 patients.

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi pii:S1684-1182(26)00123-4 [Epub ahead of print].

BACKGROUND: Understanding the clinical relevance of anti-Spike IgG antibodies in the Omicron era remains crucial for optimizing the management of vulnerable patients with COVID-19. This study aimed to evaluate the relationships between humoral immunity, virological features, and host factors in high-risk individuals infected during the Delta-Omicron transition.

METHODS: We investigated 120 high-risk patients with early COVID-19 in Italy, with sampling performed shortly after symptom onset. Humoral immunity was assessed using a quantitative anti-Spike IgG assay and an ACE2-RBD receptor-binding inhibition assay. Plasma viral load (RNAemia) and viral variant typing were performed. Multivariable regression models were used to explore associations among immune markers, virological characteristics, vaccination status, age, and comorbidities.

RESULTS: At baseline, 67.5% (81/120) of patients were IgG-seropositive and were older than seronegative individuals. Anti-Spike IgG titers correlated strongly with wild-type RBD-ACE2 binding inhibition overall (r = 0.80), with a stronger correlation in Delta infections (r = 0.91) than Omicron infections (r = 0.64). Higher IgG titers showed a trend towards lower viral load in Delta but not in Omicron infections. Omicron infection was independently associated with significantly higher RNAemia. Among seropositive patients, vaccination was associated with lower IgG titers but higher ACE2-RBD inhibition capacity. Increasing age correlated positively with IgG titers, while the number of risk factors correlated negatively. RNAemia was frequent but was not associated with long-COVID.

CONCLUSION: These findings highlight variant-specific limitations of anti-Spike IgG as a universal marker of protection and support the need for integrated serological and virological assessment to guide antiviral and monoclonal antibody strategies in vulnerable populations.

RevDate: 2026-09-16

Coen M, de Grasset J, Sader J, et al (2026)

COVID-19's illness script: From its origins to the present day. A Tinguely-like kinetic sculpture.

Journal of infection and public health, 19(11):103362 pii:S1876-0341(26)00234-0 [Epub ahead of print].

BACKGROUND: Illness scripts (IS) are mental representations of diseases formed through formal and experiential learning. Rich and mature IS are promptly activated in contextual information, expediting diagnosis and management. The COVID-19 IS developed atypically-experts had to build it without prior knowledge. This study examines its evolution from early pandemic stages to the present, assessing its richness, maturity, uncertainties, influencing factors, and its impact on clinical supervision.

METHODS: A qualitative study was conducted at Geneva University Hospitals from December 2022 to May 2023. Volunteer physicians from various divisions participated in semi-structured interviews, which were recorded, transcribed, coded, and analyzed using deductive and inductive thematic approaches. The theoretical frameworks concerning IS development, richness, and maturity, as well as situated cognition theory, were used in the analysis.

RESULTS: Twenty physicians participated. The COVID-19 IS, developed from diverse sources, is now rich and mature. COVID-19 is primarily viewed as a respiratory infection, especially in vulnerable patients, with corticosteroids and supplemental oxygen as primary treatments. However, instability remains: atypical presentations still occur, viral variants raise treatment concerns, and long COVID introduces additional complexity. Political, institutional, and individual factors shape the IS. While the IS itself was shared across seniority levels, participants reported an erosion of the supervisor's epistemic authority: attending physicians saw a threat to trainees' formation, chief residents a shift toward collaborative reasoning, and residents a move from knowledge transmission to relational support. The pandemic harmed medical training, as COVID-19 overexposure led to poor IS development for common illnesses.

CONCLUSION: Despite atypical construction, the COVID-19 IS has become rich and mature, though some uncertainties persist. Moreover, it is operational and effective. It was shaped through dynamic interactions across multiple levels-from the immediacy of patient encounters to the broader institutional and sociopolitical contexts in which clinical practice unfolds.

RevDate: 2026-09-16
CmpDate: 2026-09-15

Pawar P, Ratnakar S, V Saxena (2026)

Let-7a-5p/SHIP-1 Axis Drives SARS-CoV-2 Spike-1-Induced Microglial Pyroptosis.

International journal of molecular sciences, 27(17):.

Although persistent neurological sequelae in long COVID are reportedly well associated with neuroinflammation, the underlying regulatory mechanisms remain poorly characterized. Previously, we identified dysregulated microRNA expression, including let-7a-5p, in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S1-stimulated human microglial cells by RNA sequencing; however, how let-7a-5p regulates the S1-mediated neuroinflammatory processes remains undetermined. In the present study, we examined the functional role of let-7a-5p in alleviating S1-induced microglial inflammation in the CHME3 cell line as well as in human monocyte-derived microglia (MDMi) using a loss- and gain-of-function approach. Functional inhibition of let-7a-5p resulted in mitigating S1-induced inflammatory cytokine release and markers of pyroptosis. Mechanistically, we established SHIP-1 as a direct target of let-7a-5p using luciferase reporter assay validation. Interestingly, we noted upregulated expression of the TLR3 gene alongside TLR2/4 in S1-stimulated microglia. Although we could not establish exactly how TLR3 is stimulated in S1-induced neuroinflammatory processes, using siRNA-mediated inhibition and a pharmacological inhibitor in both CHME3 cells and MDMi, our study certainly provides evidence of TLR3 involvement during S1-induced microglial inflammation, which needs further investigation. Together, these in vitro findings demonstrate that the let-7a-5p/SHIP-1 axis regulates S1-induced inflammatory cascades in CHME3 and MDMi cells, providing mechanistic insight into its role in SARS-CoV-2-associated neuroinflammation and warranting further validation in appropriate in vivo/organoid models.

RevDate: 2026-09-15

McLaughlin E, Yonts AB, A Gourishankar (2026)

Child Opportunity Index: Paradoxical Risk of Pediatric Long COVID Cases.

Clinical pediatrics [Epub ahead of print].

Pediatric long COVID is a chronic, multisystem condition with potential physical, cognitive, and psychosocial effects. Although children in under-resourced communities experienced a disproportionate COVID-19 burden, access to post-COVID specialty care may be uneven. We conducted a retrospective cross-sectional study of 194 pediatric long COVID patients from Washington, DC, Maryland, and Virginia, who presented to a multidisciplinary tertiary care clinic between May 2021 and January 2024. Patients had a mean age of 12.8 years; 57% were female and 63% were non-Hispanic white. Most patients lived in very high-opportunity areas, while few lived in low-opportunity areas. Spatial hotspots were identified in urban and suburban census tracts, including parts of Maryland, Virginia, and Washington, DC; cold spots were identified in rural and exurban areas. These findings suggest that clinic-based pediatric long COVID presentation may reflect access to specialty evaluation as well as underlying disease burden. Broader screening and community-based approaches may help identify unmet need in under-resourced communities.

RevDate: 2026-09-15
CmpDate: 2026-09-15

Daodu L, Raste Y, Allgrove JE, et al (2026)

Exploring long covid care pathways in the UK NHS: a qualitative study of healthcare professionals' experiences.

BMJ open, 16(9):e120704 pii:bmjopen-2026-120704.

OBJECTIVES: To explore the operational reality of the long covid care pathway from the perspective of National Health Service (NHS) professionals, addressing the gap between national guidelines and frontline implementation.

DESIGN: A qualitative study using single-timepoint, semi-structured interviews. Data were collected between July and October 2024. Data were analysed using reflexive thematic analysis.

SETTING: Primary and secondary NHS care settings in a diverse South London Borough (Croydon), UK.

PARTICIPANTS: 12 NHS healthcare professionals managing adult patients, comprising general practitioners (GPs, n=5), respiratory consultants (n=2), specialist nurses (n=3), a respiratory physiotherapist (n=1) and a clinical psychologist (n=1).

RESULTS: The operational reality of long covid care was constructed around four central themes. First, lacking definitive biomarkers, clinicians navigated diagnostic uncertainty using pragmatic, exclusionary testing and subjective severity assessments. Second, GPs acted as administrative linchpins, compelled to triage patients into fragmented, symptom-driven specialist silos. Third, treatment demonstrated therapeutic pragmatism, relying heavily on non-pharmacological rehabilitation rather than medicalised cures. Finally, variable monitoring practices across secondary services created a post-discharge 'continuity gap', placing the burden of re-initiating care on the patient. These systemic frictions were synthesised into an eight-step operational care pathway map.

CONCLUSIONS: While national guidelines provide best practices, this study uniquely captures the systemic bottlenecks that occur when operationalising these standards locally. The mapped pathway reveals a pressing need for the standardisation of functional assessment tools, genuinely integrated interdisciplinary clinics and robust post-discharge tracking to mitigate the burden of coordination on primary care.

RevDate: 2026-09-15
CmpDate: 2026-09-14

Millan MJ (2026)

From HIV to SARS-CoV-2 associated neurological disorder ("HAND" to "SAND"): Viral infection as a "time-bomb" for the aging brain.

Neuroscience applied, 5:107024.

In 2020, a novel Coronavirus, Severe Acute Respiratory Syndrome-Covid-2 (SARS-CoV-2), spread globally to provoke a pandemic that infected over 750 million people. The associated disorder, Coronavirus-19 (COVID-19), has caused at least 7 million deaths and around a hundred million people have developed a variable yet sometimes incapacitating condition called Long Covid. This multi-organ syndrome, often referred to as "Brain Fog", encompasses symptoms of extreme fatigue, anxiety, poor sleep and, most prominently, cognitive impairment. Long Covid emerges three or more months after SARS-CoV-2 infection and bears a marked resemblance to the suite of neurological symptoms that evolves several years after infection with Human Immunodeficiency Virus (HIV). Accordingly, by analogy to "HIV Associated Neurological Disorder" (HAND), the acronym," SAND" is proposed for SARS-CoV-2 Associated Neurological Disorder. Mimicking HIV infection/HAND, SARS-CoV-2 infection/SAND is on a collision course with aging, leading to their mutual aggravation and an increased risk of disorders like Alzheimer's and Parkinson's disease. In contrast to HIV, where the virus crosses the blood-brain-barrier in T-lymphocytes and monocytes to infect microglia and other cell types, there is little evidence that SARS-CoV-2 enters the brain. Nonetheless, in addition to the indirect effects of a somatic hyper-inflammation ("cytokine storm") and the disruption of blood- and CSF-brain barriers, SARS-CoV-2-encoded S1 Spike protein and other virally-encoded proteins enter the brain to directly interfere with cerebral function. Microglia and astrocytes adopt a pro-inflammatory phenotype, neurotoxic proteins accumulate, mitochondrial energy generation declines, and synaptic transmission is perturbed. These findings for SAND mirror observations seen with aging and dementia. A broad-based programme of "R and D", healthcare and social support would appear desirable to better understand the complex set of interacting mechanisms underlying SAND, to prevent its onset, to alleviate the debilitating symptoms, and to improve our readiness for countering the impact of those novel, brain-damaging viruses that will inevitably arise in the future.

RevDate: 2026-09-14

Li B, Song S, Gong Y, et al (2026)

Short and Long time Impact of SARS-CoV-2 on clinical characters of Graves' Disease Patients: A Retrospective Cohort Study.

Endocrine connections pii:78203 [Epub ahead of print].

BACKGROUND: To comprehensively evaluate the effects of SARS-CoV-2 infection on treated Graves' disease (GD) patients.

METHODS: This single-center retrospective cohort study included 220 patients with GD receiving stable antithyroid drug treatment. Among 179 questionnaire respondents, 107 had confirmed SARS-CoV-2 infection and 72 were uninfected. Paired thyroid-function analyses were performed in 65 infected patients, and long COVID was assessed in 72 participants.

RESULTS: Among the cohort, 107 patients (77.1% female; 69.7% aged <60 years) were infected with SARS-CoV-2. COVID-19 vaccination was less frequent among infected than uninfected participants (70.1% vs 84.7%, P = 0.025). At 12 weeks post-infection, TT3 increased from 1.76 to 1.97 nmol/L (P = 0.032), whereas TSH, FT3, FT4, TT4, and TRAb remained unchanged. Total cholesterol and HDL-C decreased after infection. TT3 changes differed by vaccination status (P for interaction=0.019), although vaccination was not associated with biochemical thyroid-function deterioration (OR 0.88, 95% CI 0.25-3.12). Among 72 participants completing long COVID assessment, 37 (51.4%) met the operational definition; increased hair loss was the most common symptom. Smoking was associated with higher odds of long COVID (OR 5.37, 95% CI 1.05-27.36).

CONCLUSIONS: SARS-CoV-2 infection in treated GD patients was associated with modest short-term thyroid and metabolic changes in treated GD patients, while most thyroid indices remained stable. These exploratory findings highlight the need for further prospective studies.

RevDate: 2026-09-14
CmpDate: 2026-09-14

Oustric P, Leibl I, Damamme MR, et al (2026)

[Mobilization of Long Covid patients: from lived experience to the co-construction of research and care pathways].

Medecine sciences : M/S, 42(8-9):719-728.

Since 2020 Long Covid has prompted a global mobilization of patients, who have documented their symptoms, named the condition, and created support groups. This article analyses, through two associations, #ApresJ20 and Covid Long Enfants, how knowledge derived from patients' experiences has been integrated into the clinical definition of Long Covid, the organization of care pathways, and participatory research, in collaboration with clinicians and researchers. It highlights both the decisive contribution of this mobilization to the recognition and management of Long Covid and the persistent gaps in institutional support regarding prevention and investment in research and care.

RevDate: 2026-09-14
CmpDate: 2026-09-14

Aboagye NY, R Baker M, Baker K, et al (2026)

Bidirectional Associations Between Autonomic Function, Sleep Quality, and Daily Fatigue and Energy Symptoms in Long COVID: Longitudinal Digital Health Study.

JMIR cardio, 10:e99630.

BACKGROUND: Long COVID is characterized by persistent fatigue, with disrupted autonomic function and sleep disturbances frequently reported. Whether daily symptom severity influences subsequent sleep and autonomic recovery (the reverse temporal direction) remains underexplored.

OBJECTIVE: This study aimed to examine bidirectional, within-person associations between objectively measured sleep quality, nocturnal heart rate variability (HRV), and daily fatigue and energy levels in individuals reporting post-COVID fatigue symptoms.

METHODS: We conducted a longitudinal observational study using continuous wearable monitoring (Fitbit Inspire 3) in 14 individuals with long COVID over a median of 28 days (range 12-73 d), yielding 678,057 minute-level observations. Nocturnal HRV parameters (root mean square of successive differences [RMSSD], high-frequency power, low-frequency/high-frequency ratio) and sleep metrics (duration, efficiency, deep sleep, rapid eye movement [REM] sleep) were derived automatically. Fatigue (4-level scale) and energy (5-level scale, 0-100) were reported via smartphone app (FatigueSense). Two temporal linking strategies were applied: (1) prospective, linking morning/afternoon symptom reports to the previous night's sleep/HRV; and (2) reverse-direction, linking evening reports to the subsequent night's sleep/HRV. Repeated-measures correlation (rmcorr) accounted for within-person clustering; person-mean-centered (Mundlak) cumulative link mixed models disaggregated within-person from between-person effects.

RESULTS: Prospective within-person rmcorr analyses (n=260 observations, 14 participants) identified 3 associations surviving Bonferroni correction (α=.0031): sleep duration (r=-0.276, 95% CI -0.392 to -0.152; P<.001) and REM sleep (r=-0.215, 95% CI -0.342 to -0.079; P=.002) with next-day fatigue, and sleep efficiency with next-day energy in the counterintuitive negative direction (r=-0.196, 95% CI -0.317 to -0.068; P=.003). HRV metrics showed no significant within-person day-to-day associations with symptoms (HRV-RMSSD → fatigue: r=-0.064, P=.36). Mundlak models revealed that HRV-RMSSD associations were predominantly between-person: individuals with chronically higher HRV reported consistently lower fatigue (β=-1.260, 95% CI -2.231 to -0.290; P=.01) and higher energy (β=0.539, 95% CI 0.056 to 1.022; P=.03). A significant Sleep × Steps interaction (β=0.091 per SD of steps per 1000; P=.02) indicated that the protective association of longer sleep on fatigue was attenuated on more active days, consistent with a postexertional malaise pattern. In an exploratory reverse-direction analysis, evening energy (but not fatigue) showed an association with that night's HRV-RMSSD that was nominally significant but did not persist after Bonferroni correction (rmcorr: r=0.327, 95% CI 0.080 to 0.537; P=.01; α=.0050) and was supported by a log-linear mixed model (β=0.0069; P=.02).

CONCLUSIONS: In this exploratory longitudinal study, sleep duration and REM sleep showed day-to-day (within-person) associations with next-day fatigue, while HRV-RMSSD distinguished individuals with better versus worse average symptom burden. The counterintuitive sleep efficiency-energy association most plausibly reflects chance, given the null sleep efficiency-fatigue association and the multiple-testing context. The preliminary, uncorrected reverse-direction association between evening energy and nocturnal HRV-RMSSD warrants replication. Experimental work is needed to test causal mechanisms and clinical relevance.

RevDate: 2026-09-15
CmpDate: 2026-09-15

Bedir F, V Demir (2026)

Post-acute symptom persistence following SARS-CoV-2, RSV, and influenza in children: A retrospective cohort study.

Medicine, 105(37):e50497.

Persistent symptoms following acute viral respiratory infections are increasingly recognized in children. While post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; long COVID) have been extensively studied, whether comparable post-acute morbidity occurs after other major respiratory viruses and whether clinical patterns differ across pathogens remains incompletely characterized. This retrospective cohort study included children aged 0 to 18 years with reverse transcription polymerase chain reaction-confirmed SARS-CoV-2 (n = 1540), respiratory syncytial virus (RSV; n = 2150), or influenza (n = 2050) infections evaluated between January 2020 and December 2024 at a tertiary university hospital system in Istanbul, Turkey. Persistent symptoms were assessed at clinician-documented follow-up visits 4 to 6 weeks after virological diagnosis. Multivariable logistic regression identified independent predictors for each pathogen. Bonferroni correction was applied for multiple comparisons. Model calibration was assessed using the Hosmer-Lemeshow test, and discriminative ability by the area under the receiver operating characteristic curve. Among 5740 children, persistent symptoms at 4 to 6 weeks were documented in 24.0% (95% confidence interval [CI] = 22.2-25.8) with RSV, 22.0% (95% CI = 19.9-24.1) with SARS-CoV-2, and 21.2% (95% CI = 19.4-23.0) with influenza (P = .086). While overall post-acute prevalence was comparable across the 3 viruses, symptom profiles differed markedly: RSV-related post-acute morbidity was dominated by respiratory and feeding difficulties in young infants; SARS-CoV-2 predominantly produced neurocognitive and systemic complaints in school-aged children; and influenza was characterized by sustained systemic symptoms. Hypoxemia was the strongest predictor for RSV (adjusted odds ratio [aOR] = 2.4, 95% CI = 1.7-3.3), while age >6 years (aOR = 2.1, 95% CI = 1.5-2.9) and hospitalization (aOR = 1.9, 95% CI = 1.4-2.6) were leading predictors for SARS-CoV-2. Age-stratified analyses demonstrated a significant virus × age interaction (P < .001), with the highest prevalence observed after RSV among infants and after SARS-CoV-2 among school-aged children. Hosmer-Lemeshow testing confirmed adequate calibration for all models (all P > .05). Inverse probability weighting sensitivity analysis yielded consistent results. Post-acute symptom persistence following pediatric viral respiratory infections is common and follows virus-specific patterns. Overall post-acute symptom prevalence was comparable across the 3 viruses, but symptom profiles were strikingly virus-specific and age-dependent. This direct comparison of 3 major respiratory viruses demonstrates that post-acute morbidity extends beyond SARS-CoV-2 and varies by pathogen and age. These findings support the development of pathogen-informed follow-up considerations.

RevDate: 2026-09-14
CmpDate: 2026-09-11

Mohd Yusoff H, Yew SQ, Mohd Nawi A, et al (2026)

Prevalence and risk factors of adverse work outcomes among manufacturing workers with Long COVID in Malaysia - A nationwide study.

PloS one, 21(9):e0357125.

INTRODUCTION: The increasing prevalence and multiorgan involvement of Long COVID among the general population has raised concerns about the possible long-term effect of this condition among industrial workers. Therefore, this study seeks to determine the prevalence and risk factors of adverse work outcomes among Malaysian manufacturing workers affected by Long COVID.

MATERIALS AND METHODS: A cross-sectional survey was conducted using the Long COVID Questionnaire, Work-Related Quality of Life (WRQoL) Scale, and the Work Productivity and Activity Impairment (WPAI) Questionnaire, which were physically distributed to previously-COVID-19 infected participants via convenient sampling. Simple logistic regression and multiple logistic regression were used to determine the association between the various risk factors and adverse work outcomes.

RESULTS: Among the 797 participants, a quarter (24.7%) of the workers with Long COVID demonstrated poor WRQoL. A total of 12.8% and 42.4% of workers with Long COVID had issues of sickness absenteeism and sickness presenteeism, respectively. Only 6.3% of the Long COVID workers had safety issues at work. Socio-clinical factors [i.e., older age (aOR=1.02) and smoking (aOR=1.38)], Long COVID symptoms [i.e., increased number of Long COVID symptoms (aOR=1.15)], work factors [i.e., engaged in shift work (aOR=1.25), handling of chemicals hazardous to health (aOR=2.51), exposure to confined space entry (aOR=1.60), exposure to excessive noise (aOR=1.55), and manual handling (aOR=1.33)], organisational factors [i.e., absence of sickness absence policy (aOR=2.77)] were significant risk factors of adverse work outcomes among workers with Long COVID. Conversely, personal factors [i.e., informing employers about the Long COVID symptom (aOR=0.32)] had a protective effect on adverse work outcomes.

CONCLUSIONS: The impact of Long COVID on WRQoL, sickness absenteeism, sickness presenteeism, safety issues at work, as well as the multifactorial nature of adverse work outcomes highlights the need for targeted workplace interventions, supportive policies, early detection, and inclusive occupational health frameworks at the workplace.

RevDate: 2026-09-14
CmpDate: 2026-09-12

Pham B, G Stoychev (2026)

Relative Brain Perfusion Differences in a Patient With Persistent Neurocognitive and Vestibular Symptoms Associated With Post-COVID-19 Condition: A Case Report.

Cureus, 18(8):e114380.

Post-COVID-19 condition may present with persistent subjective cognitive and vestibular symptoms despite unrevealing conventional diagnostic evaluation. We report the case of a 67-year-old woman who developed persistent subjective cognitive symptoms ("brain fog"), dizziness, vertigo, and imbalance following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After an unrevealing conventional diagnostic evaluation, brain perfusion single-photon emission computed tomography (SPECT), obtained as part of the clinical evaluation, demonstrated a nonspecific mixed pattern of relative cortical and subcortical perfusion abnormalities. An individualized management plan was subsequently implemented, and during approximately five months of follow-up, the patient reported gradual improvement in subjective cognitive symptoms, balance, and daily functioning; however, because multiple interventions were introduced concurrently, the contribution of any individual intervention cannot be determined. This case describes a nonspecific pattern of relative brain perfusion abnormalities in a patient with post-COVID-19 condition. The relationship between these imaging findings and the patient's clinical symptoms remains uncertain, and this single observation does not establish the diagnostic or clinical utility of brain perfusion SPECT.

RevDate: 2026-09-14

Rizzo R, Cox RJ, García AH, et al (2026)

Editorial: The influence of SARS-CoV-2 infection and long-COVID on the incidence of viral coinfection.

Frontiers in immunology, 17:1937175.

RevDate: 2026-09-12
CmpDate: 2026-09-10

Sreelakshmi PR, Wagh P, Sarje P, et al (2026)

Distinct Cytokine Signatures and Antibody Neutralization Capacity Differentiate Post-Acute Sequelae of COVID-19 From Recovered Individuals Despite Comparable T Cell Responses.

Journal of medical virology, 98(9):e71145.

High prevalence of post-acute sequelae of COVID-19 (PASC/long COVID) has led to the determination of the pathophysiology of PASC. In a hospital-based cross-sectional survey, we assessed the clinical and immunological parameters in a set of 67 PASC and 81 recovered individuals from COVID-19 (N-PASC), to identify the immune biomarkers associated with the mechanistic cornerstone of this condition. PASC had higher chronic comorbidities, hospitalization, and ICU admissions during the COVID-19 pandemic compared to the N-PASC group. Though comparable SARS-CoV-2-specific antibodies were detected across the groups, their functionality (NAbs) was significantly higher in the N-PASC. PASC patients exhibited features of immune dysregulation, characterized by altered coordination between cellular and humoral immune responses despite broadly comparable cytokine profiles and T-cell responses. ROC analysis in hospitalized PASC and hospitalized N-PASC subjects sampled at 1, 2, and 3 years post COVID-19 supported the utility of IL-6 as a biomarker for long-term inflammatory activity. Higher FGF-basic levels in the hospitalized PASC compared to non-hospitalized PASC highlighted a potential association between elevated growth factor signaling and severity-related immune dysregulation, tissue damage that may have utility as a biomarker candidate. Our analysis supports a dysregulated crosstalk between humoral and cellular immunity in PASC patients, which could be leading to inflammation and persistent clinical symptoms associated with this debilitating condition. In conclusion, comparable T-cell and cytokine responses among long COVID and recovered individuals suggest that persistent symptoms are unlikely to be driven by impaired antiviral immunity, underscoring the potential role of immune dysregulation.

RevDate: 2026-09-11

Nasser RM (2026)

Phytotherapeutic Frontiers: A Comprehensive Review of Medicinal Plants as Adjuncts in COVID-19 Management.

Current topics in medicinal chemistry pii:CTMC-EPUB-158220 [Epub ahead of print].

Unexpected findings emerge when nature encounters pandemic challenges. From mountain slopes, remedies arise shaped by harsh climates. Such conditions foster strong chemical defenses in plants. One such defense disrupts a key virus enzyme, similar to lab-made drugs. Instead of only attacking germs, these substances also calm body reactions gone awry. They can block the spike protein's interaction with human cells while reducing excessive immune signals associated with severe illness. Structural features within these compounds may explain why some are more effective than others. Tiny carriers developed through advanced methods help them reach target sites more effectively. Evidence has accumulated gradually across recent studies. Not every plant compound is equally successful, as effectiveness depends on precise molecular interactions and stability within the body. Delivery may be as important as the compound's origin or structure. Insights come not from individual experiments alone, but from patterns observed across multiple studies. Most importantly, different levels of evidence are distinguished here, ranging from lab experiments and computer forecasts to animal tests and limited human research, with the awareness that digital results often fail in real medical settings unless confirmed through rigorous testing. Rooted in traditional plant knowledge yet guided by modern methods, this study maps a path toward discovering natural remedies while maintaining a critical assessment of whether the reported health benefits are supported by sufficient evidence.

RevDate: 2026-09-11
CmpDate: 2026-09-10

Hallberg C, Halvarsson A, Svensson A, et al (2026)

Respiratory symptoms up to 18 months after COVID-19 - a longitudinal observational study.

Respiratory research, 27(1):.

BACKGROUND: This study aimed to identify, analyse and compare adults with and without respiratory symptoms over time after COVID-19 and identify predictors of persistent respiratory symptoms, in hospitalised and non-hospitalised patients.

METHODS: Participants were recruited at the Post COVID-19 clinic at Karolinska University hospital, Sweden, between May 2020 until December 2022, with longitudinal data collected until February 2025. Data from medical records and two clinical follow-up visits were analysed. Participants were categorised based on presence or absence of self-reported respiratory symptoms. Clinical outcomes included physical function, patient-reported outcomes, lung function and other clinically relevant parameters.

RESULTS: A total of 963 out of 1976 participants were included, of whom 760 (79%) were identified with respiratory symptoms and 203 (21%) were not at first follow-up visit. The respiratory symptom group showed poorer physical function and worse patient-reported outcomes at the first follow-up (adjusted p < 0.05). Lung function was generally preserved, although diffusing lung capacity for carbon monoxide (DLCO) was lower in the respiratory symptom group (79% vs 84%, adjusted p < 0.05). Both groups improved over time, and the magnitude of change did not differ significantly between groups. However, participants in the respiratory symptom group remained more impaired across several outcomes at follow-up. Presence of respiratory symptoms at the first follow-up visit was the strongest independent predictor of belonging to the respiratory symptom group at second follow-up visit (OR 5.31, 95% CI 2.74-10.89).

CONCLUSIONS: Respiratory symptoms after acute COVID-19 were highly prevalent and were associated with poorer clinical outcomes, despite similar recovery over time. Further research is needed to better clarify underlying mechanisms and to guide targeted rehabilitation strategies.

RevDate: 2026-09-10
CmpDate: 2026-09-10

Cano-Cevallos L, Patiño-Aveiga G, Gaibor-Pazmiño A, et al (2026)

Microbiome dysbiosis in long COVID: a scoping review of mechanistic insights, symptom associations, and therapeutic targets.

Gut pathogens, 18(1):.

BACKGROUND: The human microbiome, particularly the gut microbiome, plays a critical role in host immunity, metabolism, and barrier function. Emerging evidence suggests that persistent alterations in microbiome composition-termed dysbiosis-may contribute to the development and symptom persistence of Long COVID.

AIMS: To map the available literature on microbiome dysbiosis in relation to Long COVID, identify key microbial alterations, associated symptoms, and evaluate potential microbiome-targeted interventions.

MATERIALS AND METHODS: The scoping review followed Joanna Briggs Institute (JBI) methodological guidance and was reported according to PRISMA-ScR. A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted for studies published from January 2000 to May 2025. Eligible studies included human subjects with a clinical diagnosis of Long COVID and microbiome-related outcomes. Data was charted using a standardized form and synthesized narratively and descriptively.

RESULTS: A total of 62 sources were included, most of which were narrative, conceptual, or descriptive in nature. The available literature most frequently discussed gut microbiome dysbiosis in relation to Long COVID, including reduced abundance of beneficial taxa such as Faecalibacterium prausnitzii and Bifidobacterium adolescentis, and increased abundance of opportunistic or pro-inflammatory taxa such as Ruminococcus gnavus and Clostridium innocuum. Reported or proposed associations involved fatigue, gastrointestinal symptoms, neuropsychiatric manifestations, and immune dysregulation. Evidence from respiratory and oral microbiomes was more limited. Microbiome-targeted interventions, including probiotics, prebiotics, synbiotics, diet, and fecal microbiota transplantation (FMT), were mainly proposed or discussed, with limited direct interventional evidence.

CONCLUSIONS: Current evidence suggests that microbiome alterations may be associated with Long COVID, but the available literature remains largely descriptive, observational, and hypothesis-generating. Further longitudinal and interventional studies are needed to clarify causality and determine whether microbiome-targeted strategies have therapeutic value.

RevDate: 2026-09-10
CmpDate: 2026-09-08

Kwon K, Jang CY, Kim W, et al (2026)

Kinetics of the PASC Index in Long COVID.

PloS one, 21(9):e0357670.

BACKGROUND: The post‑acute sequelae of SARS‑CoV‑2 infection (PASC, "Long COVID") remain difficult to evaluate because standardized diagnostic tools are limited. We applied the recently proposed PASC index (score ≥ 12) to describe the 12‑month trajectory of Long COVID symptoms.

METHODS: In this prospective cohort, adults with laboratory‑confirmed COVID‑19 were consecutively enrolled from November 2022 to February 2025. Long COVID was defined by a PASC index of ≥12 across 12 symptom domains persisting for at least 30 days post-infection. Symptom questionnaires were completed at 1, 3, 6 and 12 months after infection.

RESULTS: Among 183 participants, 48 (26.2%) met Long COVID criteria. Symptom assessments indicated that the proportion of participants meeting the Long COVID threshold declined from 27% at 1 month to 18% at 12 months, although this change was not statistically significant (p = 0.16). Participants classified as having Long COVID had consistently higher PASC index values across follow-up, while pairwise within-person comparisons showed no significant temporal changes in either the Long COVID or non-Long COVID group. These findings suggest that the overall symptom burden remained relatively stable over time, despite fluctuations in threshold status.

CONCLUSION: During 12 months of follow-up, approximately one quarter of participants met the PASC index threshold at least once. Among participants with repeated assessments, PASC index scores showed limited within-person change, although differential non-response limits the interpretation of temporal prevalence estimates.

RevDate: 2026-09-09
CmpDate: 2026-09-09

Lewandowska A, Sawicka D, Jóźwiak A, et al (2026)

Microvascular Dysfunction and Redox Imbalance in Long COVID.

Microcirculation (New York, N.Y. : 1994), 33(7):e70085.

OBJECTIVE: Endothelial and microvascular dysfunction are key features of Long COVID. Disturbances in cellular redox balance, reflected by altered nicotinamide adenine dinucleotide (NAD[+]/NADH) dynamics, may underlie vascular impairment. Flow-Mediated Skin Fluorescence (FMSF) evaluates microvascular function by monitoring NADH fluorescence during ischemia and reperfusion. We integrated FMSF-derived microvascular phenotyping with targeted NAD[+] metabolite profiling to determine whether altered NAD[+] metabolism is associated with impaired microvascular responses in Long COVID.

METHODS: Microvascular function was assessed in 36 patients with Long COVID and 47 age-matched controls using FMSF. NADH fluorescence changes during ischemia and hyperemia were analyzed as markers of endothelial responsiveness. NAD[+] and related metabolites were measured using high-performance liquid chromatography and mass spectrometry.

RESULTS: Patients with Long COVID showed impaired FMSF parameters, including blunted ischemic responses and delayed recovery after hyperemia, indicating microvascular dysfunction. These changes were accompanied by a reduced NAD[+]/NADH ratio and lower NADP levels, consistent with redox imbalance. Abnormal fluorescence profiles were associated with altered NAD[+] metabolism, including reduced precursor availability and accumulation of degradation products. Higher NR concentrations showed associations with selected microvascular and eNOS-related parameters.

CONCLUSIONS: FMSF provides a clinically applicable tool for detecting microvascular dysfunction in Long COVID. NAD[+] redox imbalance is linked to impaired microcirculatory responses, supporting FMSF as a functional marker of microvascular impairment associated with altered NAD[+] metabolism.

RevDate: 2026-09-09

Sakellaropoulos SG, Spedicato V, O Pfister (2026)

Exercise Lactate in Post-COVID-19 Condition: Pathophysiological Signal, Phenotyping Tool, or Candidate Biomarker? A Narrative Review with a Hypothesis-Generating Clinical Observation.

Current problems in cardiology pii:S0146-2806(26)00194-5 [Epub ahead of print].

Post-COVID-19 condition (PCC), commonly termed long COVID, is a heterogeneous multisystem disorder in which fatigue, exertional dyspnoea, post-exertional symptom exacerbation, and reduced exercise tolerance are prominent. No single laboratory measurement currently confirms or excludes PCC. Because lactate integrates glycolytic flux, pyruvate oxidation, muscle recruitment, oxygen delivery and extraction, adrenergic drive, and clearance by the liver and other tissues, exercise-associated lactate has attracted interest as a potential marker of impaired bioenergetics in PCC. This narrative review evaluates the physiological rationale and clinical evidence for lactate assessment at rest and during exercise in adults with PCC and places a descriptive observation from 22 patients assessed in our clinic into that context. Cardiopulmonary exercise testing studies demonstrate reduced peak oxygen uptake in many symptomatic individuals, although reported mechanisms include deconditioning, dysfunctional breathing, chronotropic incompetence, preload failure, impaired systemic oxygen extraction, autonomic dysfunction, and peripheral or mitochondrial abnormalities. Small mechanistic studies have reported higher exercise lactate, reduced calculated fat oxidation, altered skeletal-muscle metabolism, or more importantly impaired mitochondrial function. In our uncontrolled clinical series, mean arterial lactate increased from 1.23 ± 0.40 mmol/L at rest to 7.11 ± 2.98 mmol/L at peak exercise; the marked difference between testing protocols underscores the methodological dependence of peak values. Overall findings are heterogeneous, populations are selected, and lactate is strongly dependent on achieved work rate, exercise duration, phenotype, medications, nutritional state, and sampling time. Peak lactate alone therefore lacks the specificity, standardization, and validated thresholds required for diagnosis. Its most promising role is as one component of a standardized metabolic exercise phenotype, interpreted alongside work rate, oxygen uptake, ventilatory thresholds, respiratory exchange ratio, symptoms, and recovery kinetics. Controlled prospective studies are required before clinical implementation.

RevDate: 2026-09-09
CmpDate: 2026-09-08

Mutoli M, Rampin A, Campanile M, et al (2026)

Inflammation and iron metabolism dysregulation as hallmarks of COVID-19 severity.

Frontiers in immunology, 17:1908452.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can cause severe clinical outcomes by triggering an excessive immune response and systemic inflammation. As disease severity increases, levels of key inflammatory markers rise accordingly. Inflammation is also associated with alterations in iron metabolism, contributing to immune dysfunction. In this study, we investigated the relationship between inflammation, iron metabolism, and COVID-19 severity to identify potential biomarkers and improve understanding of disease mechanisms. We also perform an exploratory analysis to investigate whether these features associated also with long COVID-19 severity.

MATERIALS AND METHODS: We conducted a retrospective, multicentre, case-control-cross-sectional observational study including 144 COVID-19 hospitalized patients and 139 COVID-19-negative controls (individuals referred for vaccination), enrolled at two hospitals in the Lombardy region, Italy. Patients were divided into four groups according to disease severity. Laboratory parameters included serum markers of inflammation (IL-6, S100A8/A9, and C-reactive protein) and iron metabolism (iron, ferritin, hepcidin, total transferrin, and transferrin saturation). Finally, a publicly available peripheral blood mononuclear cell (PBMC) transcriptomic dataset was analyzed to evaluate whether inflammation and iron dysmetabolism associated with long COVID-19 severity.

RESULTS: COVID-19 patients exhibited a marked increase in inflammatory markers (IL-6, S100A8/A9, C-reactive protein), as well as ferritin and hepcidin, while serum iron, transferrin levels, and saturated transferrin levels were lower compared to controls. Moreover, increasing COVID-19 severity was associated with higher ferritin, inflammatory markers, white blood cell and neutrophil counts, whereas total transferrin progressively decreased with disease severity. PBMC alterations in iron metabolism and inflammation were observed in patients with severe long COVID-19.

CONCLUSIONS: Our data indicate a close association between inflammation, altered iron metabolism, and COVID-19 severity, with transcriptomic evidence supporting the persistence of these pathways in severe long COVID-19.

RevDate: 2026-09-08

Felipe TO, Héctor Fabio RG, Pietro R, et al (2026)

Effects of Viusid in Long COVID: A Randomized Double-Blind Placebo-Controlled Trial.

Infectious disorders drug targets pii:IDDT-EPUB-158201 [Epub ahead of print].

INTRODUCTION: Long COVID syndrome (LCS) is characterized by persistent neurological, respiratory, and systemic symptoms following SARS-CoV-2 infection, with limited effective treatments available. Viusid is an oral antioxidant and immunomodulatory formulation that may improve chronic inflammatory symptoms. This study evaluated the efficacy of Viusid in patients with LCS.

METHODS: This randomized double-blind placebo-controlled clinical trial evaluated the efficacy and safety of Viusid in adults with long COVID syndrome. The primary endpoint was the change in brain fog severity at Day 210. Secondary endpoints included changes in neurological, respiratory, musculoskeletal, digestive, and general symptoms measured using a 23-symptom clinical questionnaire.

RESULTS: All participants completed the study. Viusid significantly improved the primary endpoint, brain fog, compared with placebo (MD -1.23; 95% CI -2.41 to -0.005; p < 0.001). Significant improvements favoring Viusid were also observed in anxious-depressive mood (p < 0.001), sleep dis-orders (p = 0.003), fatigue (p = 0.023), dyspnea (p = 0.018), chest pain (p = 0.002), cough (p = 0.004), abdominal pain (p = 0.009), and myalgia (p = 0.025). These effects remained consistent after adjusted analyses.

DISCUSSION: The intervention showed potential improvement in long COVID symptoms; however, the small sample size and observational design limit conclusions, warranting further randomized con-trolled studies.

CONCLUSIONS: Viusid significantly improved multiple long COVID symptoms, particularly neurological and respiratory manifestations. These findings support its potential as a therapeutic option for long COVID and justify further confirmatory studies.

RevDate: 2026-09-08
CmpDate: 2026-09-05

Axon DR, SB Fenwick (2026)

Prevalence and predictors of prescription opioids among United States adults with long COVID: A nationally representative cross-sectional database study.

Medicine, 105(36):e50568.

Long COVID may occur in some patients after contracting COVID-19. Opioids are employed as one of many management and treatment strategies for this relatively new condition. However, the frequency of opioid prescribing and the characteristics of patients with long COVID prescribed an opioid are currently unknown. The objective of this exploratory study was to determine the prevalence and predictors associated with being prescribed an opioid among United States (US) adults with long COVID. This cross-sectional study included US adults (≥18 years) alive through 2023 with a diagnosis of long COVID. The 2023 Medical Expenditure Panel Survey (MEPS) full-year consolidated dataset and prescribed medication dataset were used. A multivariable logistic regression model assessed associations between the independent variables and the dependent variable (prescribed opioid vs no prescribed opioid). Independent variables were organized according to the Andersen Behavioral Model and included age, sex, race, ethnicity, marital status, education, employment, income, insurance, chronic conditions, health status, mental health status, functional limitations, pain interference, exercise, smoking status, and COVID-19 vaccination. The complex MEPS data structure was maintained, and a weighting variable was included to calculate nationally representative estimates. The alpha value (determined a priori) was 0.05. The study included 877 (weighted n = 2,17,73,754) US adults with long COVID. Of these, 144 (weighted n = 32,04,534) were prescribed an opioid while 733 (weighted n = 1,85,69,220) were not prescribed an opioid. Characteristics associated with increased odds of being prescribed an opioid included poor/low versus middle/high income (adjusted odds ratio [AOR] = 1.8, 95% confidence interval [CI] = 1.0, 3.0), having quite a bit/extreme versus no pain interference (AOR = 4.3, 95% CI = 2.1, 8.7), and being nonsmokers versus smokers (AOR = 2.7, 95% CI = 1.2, 6.2). In conclusion, the characteristics associated with being prescribed an opioid among US adults with long COVID in this MEPS database study may help inform the appropriate management of this condition. Future research is needed to establish if the prescribed opioids are being used to manage symptoms of long COVID and to ascertain the diagnoses and prescribing patterns for opioids in this population.

RevDate: 2026-09-05

Liu YK, Persaud D, Vieira EL, et al (2026)

Corrigendum to "Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms" [EBioMedicine (2026) Jul 10: 106339].

RevDate: 2026-09-08

Nolan TH, Richardson S, H Ruffieux (2025)

Efficient Bayesian functional principal component analysis of irregularly-observed multivariate curves.

Computational statistics & data analysis, 203:108094.

The analysis of multivariate functional curves has the potential to yield important scientific discoveries in domains such as healthcare, medicine, economics and social sciences. However, it is common for real-world settings to present longitudinal data that are both irregularly and sparsely observed, which introduces important challenges for the current functional data methodology. A Bayesian hierarchical framework for multivariate functional principal component analysis is proposed, which accommodates the intricacies of such irregular observation settings by flexibly pooling information across subjects and correlated curves. The model represents common latent dynamics via shared functional principal component scores, thereby effectively borrowing strength across curves while circumventing the computationally challenging task of estimating covariance matrices. These scores also provide a parsimonious representation of the major modes of joint variation of the curves and constitute interpretable scalar summaries that can be employed in follow-up analyses. Estimation is conducted using variational inference, ensuring that accurate posterior approximation and robust uncertainty quantification are achieved. The algorithm also introduces a novel variational message passing fragment for multivariate functional principal component Gaussian likelihood that enables modularity and reuse across models. Detailed simulations assess the effectiveness of the approach in sharing information from sparse and irregularly sampled multivariate curves. The methodology is also exploited to estimate the molecular disease courses of individual patients with SARS-CoV-2 infection and characterise patient heterogeneity in recovery outcomes; this study reveals key coordinated dynamics across the immune, inflammatory and metabolic systems, which are associated with long-COVID symptoms up to one year post disease onset. The approach is implemented in the R package bayesFPCA.

RevDate: 2026-09-05
CmpDate: 2026-09-05

Garnier N, Ossi J, Marconi VC, et al (2026)

Targeting the JAK/STAT pathway in chronic viral infections: opportunities and challenges for immunomodulation.

Frontiers in immunology, 17:1887876.

The discovery of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway as a key regulator of immune function and inflammation led to the development of JAK inhibitors (JAK-i), several of which are now approved for autoimmune and chronic inflammatory conditions. Recently, JAK-i have been repurposed for infectious diseases, most notably with baricitinib, a United States Food and Drug Administration (FDA)-approved JAK1/2 inhibitor for individuals hospitalized for COVID-19, demonstrating a survival benefit by dampening cytokine-mediated hyperinflammation. This has generated increased interest in leveraging JAK-i for treating people with viral infections associated with chronic immune activation, inflammation or viral persistence. This review summarizes JAK/STAT signaling in viral infections characterized by latency or chronic sequelae. We explore how modulation of this pathway may alter immune responses, impact viral control, and mitigate the consequences of chronic inflammation. We also critically examine the therapeutic potential and limitations of JAK-i in these contexts. Finally, we outline key gaps in the field and propose future directions for research into JAK/STAT targeted immunomodulation in chronic viral infections.

RevDate: 2026-09-04
CmpDate: 2026-09-04

Hunter E, Alshaker H, Vugrinec D, et al (2026)

Beyond genes: EpiSwitch® and Orion platform-powered 3D genome architecture biomarkers reveal shared biology across ME/CFS, long COVID, PTSD, rheumatoid arthritis, and multiple sclerosis.

Journal of translational medicine, 24(1):.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Long COVID (LC19), post-traumatic stress disorder (PTSD), rheumatoid arthritis (RA), and multiple sclerosis (MS) are clinically distinct disorders that share substantial symptom overlap, including persistent fatigue, cognitive impairment, autonomic dysfunction, and immune dysregulation. Although these conditions differ in diagnosis and clinical presentation, their underlying biological mechanisms remain poorly understood and may involve convergent regulatory pathways.

METHODS: The EpiSwitch® 3D genomics platform and Orion knowledgebase were used to integrate chromosome conformation signatures with genome-wide association study (GWAS)-derived datasets across ME/CFS, LC19, PTSD, RA, and MS. Three-dimensional genomic anchors were mapped to coding genes and analysed using STRING protein-protein interaction networks and Cytoscape-based systems biology approaches. Disease-specific anchor datasets were generated and compared at both gene and network levels to identify shared biological processes and regulatory mechanisms.

RESULTS: Analysis of the ME/CFS dataset identified 552 unique 3D genomic anchors mapped to 567 genes, with analogous disease-specific anchor sets generated for LC19, PTSD, RA, and MS. Direct overlap between disease-associated genes was limited; however, higher-order network analyses revealed substantial interconnectivity and convergence across conditions. Shared biological pathways included immune and cytokine signalling, interferon responses, mitochondrial function, metabolic regulation, and neuroendocrine processes. Highly connected hub genes included immune regulatory nodes such as LAG3 and components of the mTOR signalling pathway, implicating T-cell exhaustion, chronic immune activation, and immunometabolic dysregulation as common mechanisms underlying these disorders.

CONCLUSIONS: These findings support a systems-level model in which clinically overlapping fatigue-associated syndromes arise from perturbations of interconnected regulatory networks rather than discrete disease-specific pathways. Despite limited genetic overlap, substantial convergence at the network level suggests shared biological architecture across ME/CFS, LC19, PTSD, RA, and MS. The identification of common regulatory pathways provides a mechanistic framework for the development of cross-disease diagnostic and therapeutic strategies. By capturing dynamic regulatory states, 3D genomic biomarkers offer significant potential for objective blood-based diagnostics, patient stratification, and the identification of shared therapeutic targets across complex chronic disorders. These findings support the application of precision medicine approaches and may accelerate the development of novel interventions for fatigue-associated multisystem diseases.

RevDate: 2026-09-05
CmpDate: 2026-09-04

Ono R, Takayama S, Abe M, et al (2026)

Persistent mitochondrial and endothelial dysfunction in non-hospitalized patients with Long COVID.

Frontiers in medicine, 13:1921822.

Long COVID, a major post-acute infection syndrome (PAIS), characterized by prolonged or new-onset symptoms following acute COVID-19, critically affects patients' quality of life. Establishing easily measurable and objective biomarkers that reflect disease severity is essential for clinical management. This retrospective cohort study evaluated serum levels of growth differentiation factor 15 (GDF-15), a mitochondrial stress marker, and vascular cell adhesion molecule-1 (VCAM-1), a vascular endothelial stress marker, in 32 patients with Long COVID who presented with persistent systemic or neurological symptoms and had not required acute-phase hospitalization. Serum GDF-15, VCAM-1, and inflammatory cytokine levels were measured at the initial visit and at 3 and 6 months. Differences between patients who recovered at 6 months and those who did not (non-improved group) were analyzed using linear mixed-effects models (LMMs). Most inflammatory cytokines remained near their lower detection limits and were excluded from the longitudinal analysis. The LMMs revealed sustained elevation of both GDF-15 (p = 0.02) and VCAM-1 (p = 0.03) levels in the non-improved group. These findings suggest that longitudinal tracking of these two markers may offer clinically relevant insights into disease activity and treatment-resistant pathophysiology in mild acute-phase Long COVID.

RevDate: 2026-09-04

Finkelstein P (2026)

Disabling Dynamics: Long Covid and the Challenges of Securitizing Slow-Onset Health Threats.

The Journal of medical humanities pii:10.1007/s10912-026-10058-x [Epub ahead of print].

This paper investigates why the United States fully securitized acute Covid-19 but not Long Covid, despite the latter's potentially greater long-term socioeconomic burden. Drawing on securitization theory, riskification, and scholarship on slow-onset and delayed-onset threats, it develops a four-part theoretical framework to explain structural variation in security responses: (1) actor framing and audience uptake; (2) the spatiotemporal visibility of harm; (3) a systemic 'body count bias' that privileges mortality over morbidity; and (4) domestic and international disincentives that suppress sustained attention to chronic, ambiguous crises. Using a most-similar systems design, the study compares U.S. governmental discourse, policy actions, and media framings of acute Covid-19-marked by temporal compression, spectacular mortality, and rapid elite mobilization-with the diffuse, bottom-up emergence of Long Covid, characterized by invisible, dispersed, and medically uncertain disability. The analysis shows that Long Covid's slow-creeping trajectory, lack of spectacle, and association with stigmatized or marginalized populations prevent it from being framed as an existential threat to a clearly identifiable referent object, relegating it instead to technocratic risk management. The study concludes that the U.S. security apparatus is structurally ill-equipped to recognize and respond to slow-onset, disabling threats, leaving the country vulnerable not only to Long Covid's long-term societal effects but to future mass-disabling events-natural or engineered-that erode state capacity gradually rather than through acute, lethal shock.

RevDate: 2026-09-04

Roy A, Chandran DS, Jaryal A, et al (2026)

Baroreflex-dependent Cardiovascular Autonomic Reactivity is Deranged in Young Adult Mild COVID-19 Survivors.

Annals of neurosciences [Epub ahead of print].

BACKGROUND: COVID-19 has subacute as well as long-term effects defined as long COVID on multiple organ systems. Emerging literature suggests long-term effects of COVID-19 on the autonomic nervous system in survivors, the mechanistic basis of which is currently not delineated.

PURPOSE: The study aimed to assess the cardiovascular autonomic functions in mild COVID-19 survivors and compare them with age- and sex-matched healthy controls.

METHODS: We recruited 34 young adult mild COVID-19 survivors. Autonomic function was assessed by cardiovascular autonomic reactivity tests at least 1 month after clinical recovery from acute COVID-19 infection. The responses were compared with those of 34 age- and sex-matched pre-COVID era healthy controls.

RESULTS: Mild COVID-19 survivors had significantly lower Valsalva ratio (1.578 ± 0.2747 vs 1.773 ± 0.3459; p = .0156) and displayed a greater fall in systolic blood pressure during head-up tilt test (-9.206 ± 7.121 vs 1.147 ± 8.457; p < .0001) in comparison to the healthy controls. Haemodynamic cardiovascular autonomic abnormalities were seen in 47% of COVID-19 survivors. Haemodynamic criteria of orthostatic hypotension were met in 12% of COVID-19 survivors, and postural orthostatic tachycardia syndrome haemodynamic criteria were met in 35% of COVID-19 survivors. Autonomic reflex responses to deep breathing, handgrip test and cold pressor test were found to be comparable between the two groups.

CONCLUSION: Young adult mild COVID-19 survivors show lower cardiovagal and cardiovascular adrenergic responses to baroreflex-dependent autonomic reactivity as medium- to long-term autonomic sequelae. They have an intact non-baroreflex-dependent autonomic reactivity.

RevDate: 2026-09-04
CmpDate: 2026-09-03

Wang Y, Zhuo H, L Wang (2026)

Advances in the clinical application of stellate ganglion block for non-pain indications.

Frontiers in medicine, 13:1840174.

BACKGROUND: Stellate ganglion block (SGB) is a peripheral nerve block technique involving injection of local anesthetics and/or steroids near the stellate ganglion. Traditionally used for pain-related syndromes, SGB has recently expanded into non-pain fields with the advancement of ultrasound guidance, showing therapeutic potential in arrhythmias, menopausal hot flashes, psychiatric disorders, cerebrovascular diseases, insomnia, and COVID-19 sequelae.

OBJECTIVE: To review the current evidence on SGB applications in non-pain conditions, evaluate its therapeutic efficacy and safety across different diseases, elucidate underlying mechanisms, and identify research gaps and future directions.

METHODS: This narrative review synthesized data from published literature including case reports, cohort studies, and randomized controlled trials (RCTs) on SGB in non-pain conditions. Studies were analyzed based on disease categories, with focus on mechanism of action, clinical outcomes, and safety profiles.

RESULTS: Stellate ganglion block demonstrates therapeutic effects across six domains: (1) Ventricular arrhythmias: In a multicenter observational study of 131 patients (the STAR study), 92% (106/115) of patients with treatable arrhythmic episodes achieved a ≥50% reduction in arrhythmia burden within 12 h via sympathetic blockade and QT dispersion reduction; (2) Menopausal hot flashes: Significant reduction in frequency through modulation of thermoregulatory pathways; (3) Insomnia: Improved sleep quality via autonomic balance restoration; (4) Cerebrovascular diseases: Enhanced cerebral perfusion and cognitive function; (5) Post-Traumatic Stress Disorder (PTSD): Case series have reported response rates of 70%-75% via inhibition of locus coeruleus-norepinephrine circuits; randomized evidence is mixed-a small early trial found no benefit over sham, whereas the subsequent multicenter randomized controlled trial (n = 113) demonstrated a statistically significant reduction in PTSD symptom severity (P = 0.01)-and adequately powered confirmatory trials are still needed; (6) COVID-19: Retrospective cohort studies suggest symptom relief in the majority of patients through autonomic reset.

CONCLUSION: Stellate ganglion block has become an important intervention for autonomic dysfunction in non-pain conditions through sympathetic blockade, neuroendocrine modulation, and anti-inflammatory effects. Although ultrasound guidance has improved safety, evidence remains limited by small RCTs, heterogeneous protocols, and observational designs. Rigorous multicenter RCTs are needed to confirm efficacy, define patient selection, and standardize protocols. Further research should investigate central regulatory mechanisms and long-term neuroplasticity to advance SGB from empirical therapy to precision intervention.

RevDate: 2026-09-03

Cossarizza A, Poli G, M Clerici (2026)

The Silent Infection Load: How Lifelong Asymptomatic Infections May Contribute to Inflammaging as an Evolutionary Trade-off of Longevity.

Ageing research reviews pii:S1568-1637(26)00332-6 [Epub ahead of print].

Asymptomatic infections are traditionally considered harmless, reflecting effective immune control and the absence of clinical disease. Yet growing evidence shows that these silent encounters with microbes are far from being immunologically neutral. Throughout life, humans are challenged by a remarkably broad spectrum of viruses and bacteria, including latent pathogens that persist, fluctuate, or periodically reactivate without producing significant symptoms. From an evolutionary standpoint, this represents a fundamental trade-off. Long-lived hosts benefit from maintaining diverse commensal, latent, and low-grade persistent microbes that enhance immune readiness, promote cross-protective immunity, and reduce vulnerability to severe infections. However, this adaptive advantage is counterbalanced by the continuous burden of chronic, almost undetectable immune activation and inflammation, and by the energetic cost of sustaining such mechanisms of surveillance. In this regard, retroviral integrations provide a striking illustration of how persistent viral presence has shaped the evolution of complex organisms by introducing new regulatory elements, immune modulators, and developmental programs. These ancient viral imprints demonstrate that clinically-silent host-microbe interactions can exert long-term selective pressures and influence species-specific biological trajectories. At the individual level, repeated asymptomatic infections trigger transient waves of immune activation, endothelial perturbation, mitochondrial stress, and complement engagement. Although each episode is mild and self-limited, their cumulative burden generates micro-damage that accelerates immunosenescence, perturbs metabolic and vascular homeostasis, and contributes to the progressive rise in systemic inflammation characteristic of aging. Notably, in the context of the recent pandemics of SARS-CoV-2 infection, the emergence of Long COVID has highlighted how even clinically mild or initially asymptomatic infections can leave durable immunological, metabolic, and neurological traces, reinforcing the concept that "silent" infections may have lasting consequences.

RevDate: 2026-09-03
CmpDate: 2026-09-02

Ng KL, Saunders L, Collier G, et al (2026)

Using hyperpolarised xenon magnetic resonance imaging to explore breathlessness in long COVID: results from the EXPLAIN study.

ERJ open research, 12(5):.

BACKGROUND: Breathlessness is a common symptom in long COVID (LC). Using hyperpolarised xenon magnetic resonance imaging ([129]Xe-MRI), we assessed whether this symptom could be attributed to abnormalities in the alveolar-capillary membrane not detected by standard investigations. We focused on never-hospitalised individuals without an identified cause for breathlessness.

METHODS: In this prospective, multicentre study, we compared [129]Xe-MRI, lung function, exercise capacity and symptom questionnaires in LC patients with breathlessness (BLC) to those without breathlessness (NBLC) and healthy controls. Primary outcome was whether BLC demonstrated measurable impairments in gas exchange focusing on dissolved-phase [129]Xe-MRI metrics: red blood cell to membrane ratio (RBC:M) and red blood cell to gas ratio (RBC:Gas). We also explored associations between symptoms and physiological measures.

RESULTS: Of 269 participants recruited, 196 were included in the analysis (109 BLC, 43 NBLC, 44 controls), with age and sex well matched across groups. BLC had a significantly longer interval from infection to MRI (median 632 days; p<0.001). No significant differences in global or regional RBC:M or RBC:Gas were observed across groups. BLC showed lower forced expiratory volume in 1 s, forced vital capacity, transfer factor of the lung for carbon monoxide (T L CO), and carbon monoxide transfer coefficient (K CO) z-scores compared to controls, though >90% of values remained within normal range. A subset of BLC participants with low T L CO (14 out of 109) showed reduced [129]Xe-MRI metrics and higher breathlessness scores.

INTERPRETATION: Most nonhospitalised LC participants exhibited no detectable pulmonary abnormalities, including those with breathlessness. However, ∼13% of breathless individuals demonstrated minor reductions in T L CO and [129]Xe-MRI gas exchange suggesting a potential pulmonary contribution for symptoms in this subgroup.

RevDate: 2026-09-03

Vishnevetsky A, Wilcox DR, Farhad K, et al (2024)

Long-Term Neurologic Complications of COVID-19: A Practical Overview The authors present an overview of the presentation and management of common neurologic symptoms associated with long COVID.

Practical neurology (Fort Washington, Pa.), 23(6):8-13.

RevDate: 2026-09-02
CmpDate: 2026-09-02

Helmsdal G, Petersen MS, MF Kristiansen (2026)

Pandemic research in a small island society-a narrative review of research contributions during the SARS-CoV-2 pandemic in the Faroe Islands.

International journal of circumpolar health, 85(1):2727219.

Small and geographically isolated societies face distinct challenges during a pandemic but may also possess advantages. This narrative literature review presents epidemiological, immunological and psychological studies conducted in the Faroe Islands during the SARS-CoV-2 pandemic, examining its effects on individuals in the Faroe Islands. The COVID-19 pandemic hit the Faroe Islands early in March 2020. With only around 55,000 inhabitants, the Faroe Islands' isolated, well-documented population enabled extensive epidemiological research and close monitoring of infection patterns. This resulted in studies on transmission, immunity, mental health and long COVID. Overall, the Faroese studies demonstrate how small, cohesive societies with robust infrastructure can conduct high-quality research during a crisis, contributing to both local and global knowledge.

RevDate: 2026-09-03

Makin S (2026)

When do infections lead to long COVID? Scientists close in on triggers and treatments for post-viral syndromes.

Nature, 657(8130):26-28.

RevDate: 2026-08-31

Kumai T, Nishi K, Tanaka A, et al (2026)

Diagnostic criteria and clinical outcomes of chronic nasopharyngitis treated with nasopharyngeal abrasive therapy: A multicenter prospective study.

Auris, nasus, larynx pii:S0385-8146(26)00126-4 [Epub ahead of print].

OBJECTIVE: Chronic nasopharyngitis is an under-recognized clinical condition, although the nasopharynx may serve as a source of persistent local and systemic symptoms. This study aimed to define diagnostic criteria for chronic nasopharyngitis and to prospectively evaluate changes in symptoms and endoscopic changes following nasopharyngeal abrasive therapy (EAT).

METHODS: A multicenter prospective observational study. Patients with chronic nasopharyngitis treated between April 2022 and March 2025. Of 219 enrolled patients, 175 were included in the final analysis. EAT was administered weekly for two months using a transnasal or transoral cotton swab soaked in 1% zinc chloride. Nasopharyngeal endoscopic findings were prospectively graded using a three-point scoring system. Symptoms were assessed using a visual analog scale (VAS).

RESULTS: Chronic nasopharyngitis was defined as persistent nasopharyngeal-related local or systemic symptoms lasting longer than one month, refractory to pharmacologic therapy, with endoscopic evidence of nasopharyngeal inflammation. The most common chief complaints were postnasal drip, general fatigue, and globus sensation. Median VAS scores for chief complaints decreased from 90 at baseline to 60 after one month and to 25 after two months. Improvements in endoscopic findings and symptoms were observed across local and systemic manifestations, including in patients with long COVID. Patients with severe nasopharyngitis demonstrated less pronounced symptom improvement.

CONCLUSION: This multicenter prospective study proposes diagnostic criteria for chronic nasopharyngitis and shows that EAT was associated with improvement in symptoms and endoscopic inflammation. These findings suggest that targeted nasopharyngeal therapy may represent a clinically relevant approach for chronic nasopharyngitis, including cases with systemic symptoms, although controlled studies are required to establish its therapeutic efficacy.

RevDate: 2026-09-02
CmpDate: 2026-09-01

Hamberger J, Kraus L, Meissner K, et al (2026)

Healthcare utilization patterns and medication burden in post-COVID syndrome: a cross-sectional analysis reveals four phenotypes.

Frontiers in health services, 6:1838358.

Post-COVID syndrome has emerged as a major public health challenge, yet comprehensive characterization of healthcare utilization patterns and medication burden within single cohorts remains limited. This cross-sectional analysis examined baseline data from 76 patients (49 ± 12 years, 62% female) enrolled in a randomized trial of psychosomatic treatment interventions for functional post-COVID syndrome. Participants completed the Health Care Utilization Questionnaire (HCU) assessing physician visits, hospitalizations, alternative healing methods, and other healthcare services over the preceding 12 months. Medication and other preparation (MOP) use was systematically documented and classified using the Anatomical Therapeutic Chemical (ATC) classification system. K-means clustering identified distinct patient phenotypes, and correlations between MOP count and healthcare utilization were examined using Spearman correlation coefficients. Healthcare utilization was universal, with 100% of participants engaging with healthcare services and a mean of 43.5 contacts per year. Medication burden was substantial, with 85.5% taking at least one medication, a mean of 4.57 medications per patient, and polypharmacy (≥5 MOP, all types) present in 39.5% of the cohort (46.1% of patients with any MOP). K-means clustering identified four distinct patient phenotypes: Low Utilizers (64.5%, n = 49), Moderate-High Utilizers (27.6%, n = 21), High-Intensity Users (6.6%), and one outlier. High-Intensity Users demonstrated the most striking profile with 9.60 mean medications, 75.0 total healthcare contacts annually, and mean out-of-pocket costs of €2,881. MOP count showed significant positive correlations with total doctor visits (ρ = 0.471, p < 0.001), total healthcare contacts (ρ = 0.344, p = 0.002), and out-of-pocket costs (ρ = 0.375, p = 0.001). Post-COVID syndrome patients demonstrate high healthcare engagement, substantial medication burden, and meaningful heterogeneity in utilization patterns. The identification of distinct patient clusters and strong correlations between medication burden and healthcare utilization provide insights for developing targeted clinical management strategies. This study is based on a selected clinical cohort, and findings should be interpreted with caution regarding generalizability to the broader post-COVID population. These findings may inform clinical management strategies and health system planning for post-COVID patients.

RevDate: 2026-09-01

Degen CV, Niewolik J, Mücke U, et al (2026)

Olfactory and gustatory perception in adults with long COVID.

American journal of otolaryngology, 47(5):104918 pii:S0196-0709(26)00134-1 [Epub ahead of print].

INTRODUCTION: Olfactory dysfunction is a common symptom in COVID-19 and Long COVID. However it is unclear how well perceived impairment of olfactory and gustatory dysfunction correlate with the objectively measured intensity of olfactory dysfunction among adults with Long COVID compared to healthy never-SARS-CoV-2-infected and previously infected control cohorts.

MATERIALS AND METHODS: We recruited 154 participants from an online Long COVID survey (DEFEAT Corona) for in-person examinations. Participants were allocated to three groups: Long COVID (persistent symptoms >4 weeks post-infection, n=122), Ex COVID (fully recovered, n=9), and No Covid (no history of infection, n=24). All participants completed questionnaires regarding demographics, perceived olfactory and gustatory function and underwent the standardized Sniffin Sticks olfactory test and gustatory testing.

RESULTS: Long COVID participants performed significantly worse on both olfactory and gustatory function tests compared to No COVID controls. Subjective assessment of olfactory and gustatory function only weakly correlated with objective test performance in the Long COVID group (r=-0.525, p<0.001). Time since COVID-19 infection did not correlate with dysfunction severity in either Long COVID or Ex COVID group.

CONCLUSIONS: Olfactory and gustatory dysfunction was more common in the Long COVID cohort than in controls. As self-perceived sensory impairment only weakly correlated with objective measures, routine screening for sensory dysfunction should be considered in Long COVID management. These impairments may significantly impact mental health and quality of life and effective treatment options like olfactory training are available.

RevDate: 2026-08-31

Mischke M, T Zaehle (2026)

Impaired auditory sensory gating as a neurophysiological correlate of cognitive fatigue in long COVID.

Neuropsychology pii:2028-18753-001 [Epub ahead of print].

OBJECTIVE: Fatigue is among the most disabling symptoms across neurological and postinfectious conditions and is a defining feature of long COVID, yet objective neurophysiological markers remain scarce. Auditory sensory gating, indexed by P50 suppression, has been proposed as a correlate of cognitive fatigue in multiple sclerosis, but its relevance in long COVID is unclear. Additionally, we compared the utility of the Beck Depression Inventory-II and Beck Depression Inventory-Fast Screen (BDI-FS) in this fatigued population.

METHOD: Seventy-one individuals with long COVID-related fatigue completed questionnaires assessing fatigue (Modified Fatigue Impact Scale) and depressive symptoms (BDI-FS). Auditory sensory gating was assessed using a paired-click electroencephalography paradigm. Auditory sensory gating was assessed using a paired-click electroencephalography paradigm. Associations between cognitive fatigue, sensory gating, and depressive symptoms were examined using correlational analyses and two hierarchical regression models.

RESULTS: Reduced P50 suppression was associated with higher Modified Fatigue Impact Scale cognitive scores (τ = -.173, p = .037). Cognitive fatigue correlated with depressive symptoms measured by the Beck Depression Inventory-II (τ = .239, p = .005), but not by the BDI-FS (τ = .131, p = .135). Neither depression measure correlated with sensory gating. P50 suppression accounted for unique variance in cognitive fatigue beyond demographics and depressive symptoms.

CONCLUSIONS: Auditory sensory gating shows a small but meaningful association with cognitive fatigue in long COVID and contributes uniquely beyond depressive symptoms. The BDI-FS demonstrated less symptom overlap, supporting its suitability for depression screening in fatigued populations. These findings underscore the importance of distinguishing fatigue related from affective symptoms and suggest sensory gating as a promising transdiagnostic target in fatigue research. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

RevDate: 2026-08-31

Baden LR, Shah NS, Liu STH, et al (2026)

Nirmatrelvir-ritonavir targeting viral persistence in post-COVID-19 condition (long COVID) in the USA (RECOVER-VITAL): a randomised, double-blind, placebo-controlled, phase 2 trial.

The Lancet. Infectious diseases pii:S1473-3099(26)00406-8 [Epub ahead of print].

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection, more commonly known as long COVID, has emerged as a major health problem. The pathogenesis of long COVID is unknown, but among the leading hypotheses is viral persistence. We aimed to investigate whether the use of the SARS-CoV-2 antiviral nirmatrelvir-ritonavir improved long COVID symptoms.

METHODS: We conducted a double-blind, placebo-controlled, randomised trial involving adults who had developed persistent symptoms (≥12 weeks) associated with three major symptom phenotypes (cognitive, autonomic, or exercise) after acute SARS-CoV-2 infection at 69 US sites. Participants were eligible if they were 18 years or older and had a previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization. Eligible participants were also required to have either at least two moderate symptoms from the same phenotype or one severe phenotype-associated symptom, as identified with the Cluster Targeted COVID-19 Symptom Questions. Participants were randomly allocated in a double-blind manner in a 1:1:1 ratio using permuted blocks of size 30 to receive either 15 days of active intervention followed by 10 days of placebo (300 mg nirmatrelvir-100 mg ritonavir twice daily, then 100 mg ritonavir-placebo); 25 days of active intervention (300 mg nirmatrelvir-100 mg ritonavir twice daily); or 25 days of placebo-ritonavir (100 mg ritonavir-placebo). A clinically significant change in patient-reported outcomes at day 90 comprised the primary endpoint: Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form 8a, Orthostatic Hypotension Questionnaire question 1, and a modified version of the DePaul Symptom Questionnaire Post-Exertional Malaise short form. Secondary outcomes were phenotype-specific performance measures. The study was registered at ClinicalTrials.gov (NCT05595369) and is complete.

FINDINGS: Between July 27, 2023, and Sept 6, 2024, 1207 individuals were screened. Of these, 964 were randomly allocated and 959 participants, excluding four participants who were later found ineligible and one who did not initiate treatment, were enrolled in the three phenotypes: 332 to cognitive, 334 to autonomic, and 332 to exercise. In the 959 participants in the mITT population, 643 (67%) self-reported as female, 314 (33%) were male, and two participants had a sex of unknown or undifferentiated; 750 (78%) were White; and 108 (11%) were Hispanic, Latino, or Spanish. The median age was 49 years (IQR 38-59). No statistically significant benefits were observed for any phenotype for primary endpoints. For the cognitive phenotype, adjusted differences compared to placebo were 3·2% (95% CI -10·4 to 16·8, p=0·65) for the 25-day regimen and -2·2% (-15·5 to 11·1, p=0·74) for the 15-day regimen. For the autonomic phenotype, adjusted differences were -6·4% (-18·5 to 5·7, p=0·30) for the 25-day regimen compared to placebo and -0·1% (-12·5 to 12·3, p=0·99) for the 15-day regimen compared to placebo. For exercise, adjusted differences were -7·8% (-19·5 to 3·8, p=0·19) for the 25-day regimen compared to placebo and 0·9% (-11·4 to 13·2, p=0·88) for the 15-day regimen compared to placebo. There were no differences in secondary endpoints, and no safety signals were observed; there were no deaths, and 52 serious adverse events occurred in 42 (4%) of 963 participants over the course of the study.

INTERPRETATION: Nirmatrelvir-ritonavir for 15 days or 25 days showed no evidence of benefit in long COVID in any of the three phenotypes studied. These findings suggest additional approaches to measuring the symptom burden and treating Long COVID are needed.

FUNDING: National Institutes of Health.

RevDate: 2026-08-30
CmpDate: 2026-08-29

Lemogne C (2026)

Long COVID in the general population: reassurance without dismissal.

The Lancet regional health. Europe, 69:101829.

RevDate: 2026-08-29

Zhang D, Chen C, Xie Y, et al (2026)

Gut Microbiota from Patients with Long COVID Persisting for 2 Years Result in Alterations in Mice that Resemble Post-COVID Symptoms.

Probiotics and antimicrobial proteins [Epub ahead of print].

Human gut microbiota (GM) has been identified as a potentially important factor influencing the development of long COVID (LCOVID). The aim of this study was to understand the GM of LCOVID, which lasted for two years, in order to improve public awareness. Human gut microbiota and its metabolites were assessed in a healthy control group (n = 11) (HC) unexposed to SARS-CoV-2 and an LCOVID group (n = 11) in Hainan, China, using Shotgun metagenomics and liquid chromatography-mass spectrometry (LC-MS) of feces. The causal role of the microbiota in LCOVID was further validated by transplanting feces from the subjects into ABx mice using Histopathology and 16 S rRNA sequencing. Fecal microbial diversity was lower in patients with LCOVID compared with that in HC. Pro-inflammatory bacteria such as Streptococcus_salivarius and Streptococcus_parasanguinis increased, whereas anti-inflammatory bacteria such as Faecalibacterium_SGB15346 and Alistipes_onderdonkii decreased. Fecal metabolites from LCOVID were impaired in carbohydrate degradation, indole production, SCFA production, and fatty acid degradation. Transplantation of feces from patients with LCOVID into mice results in lung inflammation, intestinal inflammation, and anxiety. In addition, transplanted mice showed worse outcomes during Klebsiella_pneumoniae infections. Transplanted mice and the key bacteria Streptococcus_salivarius had the same worse outcomes in the D-IBS model by limb binding. GM from patients with LCOVID was altered significantly and sufficiently to promote LCOVID symptoms in mice, suggesting that it may be a potential therapeutic target.

RevDate: 2026-08-31

Hasan Ö, Abidin K, Halil Ö, et al (2026)

Persistent fibroblast-related tissue activity in long COVID after moderate-to-severe acute COVID-19 assessed by [[68]Ga]Ga-FAPI PET/CT.

Revista espanola de medicina nuclear e imagen molecular pii:S2253-8089(26)00066-2 [Epub ahead of print].

PURPOSE: Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms. Fibroblast activation protein (FAP), expressed on activated fibroblasts during tissue remodeling, can be visualized with [[68]Ga]Ga-FAPI PET/CT. This study investigated lung and muscle fibroblastic activity in patients with post-acute sequelae of COVID-19 (PASC) following moderate-to-severe COVID-19 pneumonia more than two years after the acute infection, using [[68]Ga]Ga-FAPI PET/CT.

METHODS: In this pilot prospective observational study, we enrolled patients with PASC following severe acute COVID-19 requiring high-flow nasal cannula or mechanical ventilation and age- and sex-matched controls without pulmonary pathology between September 2023 and February 2024. PASC patients underwent high-resolution CT (HRCT), pulmonary function tests (PFTs), and [⁶⁸Ga]Ga-FAPI PET/CT. SUVmax and SUVmean were measured for each lung lobe. HRCT abnormalities were scored using a semi-quantitative scale (0-20) and categorized as ground-glass opacities, reticulations, parenchymal bands, traction bronchiectasis, or subpleural cysts. These findings were statistically compared and correlated with PET parameters, PFTs, and clinical symptoms. In addition, [⁶⁸Ga]Ga-FAPI uptake in the paravertebral muscles was assessed at the level of the L3 vertebra.

RESULTS: Twenty patients with PASC and 10 control subjects were included (median ages: 64 and 58.5 years, respectively). The mean interval between hospitalization for acute COVID-19 and study imaging was 25 ± 4.5 months. PASC patients exhibited significantly increased [⁶⁸Ga]Ga-FAPI uptake in the lungs compared with controls. Lung [⁶⁸Ga]Ga-FAPI uptake was markedly increased in patients with traction bronchiectasis. No correlations were observed between lung [⁶⁸Ga]Ga-FAPI SUVmax and PFTs or symptom burden. However, lung [⁶⁸Ga]Ga-FAPI SUVmean demonstrated moderate inverse correlation with DLCO (r = -0.455, p = 0.044). In addition, [⁶⁸Ga]Ga-FAPI SUVmax in muscle was significantly higher in PASC patients than in controls, with particularly elevated uptake observed in patients with a history of mechanical ventilation.

CONCLUSIONS: [⁶⁸Ga]Ga-FAPI PET/CT demonstrated increased lung tracer uptake in patients with PASC more than two years after moderate to severe COVID-19, supporting persistent fibroblast-related tissue activity. Limited associations between lung SUVmean and DLCO suggest a potential link between tracer uptake and functional impairment. Increased muscle [⁶⁸Ga]Ga-FAPI uptake was also observed as an exploratory finding requiring further functional and histopathological validation.

RevDate: 2026-08-31

Rudroff T (2026)

Fatigue in Neurological Rehabilitation: Why Brain Diversity and Population Diversity Matter.

Neurorehabilitation and neural repair [Epub ahead of print].

BACKGROUND: Fatigue affects 50% to 90% of patients with multiple sclerosis, Parkinson's disease, stroke, ME/CFS, and long COVID and represents a primary barrier to rehabilitation participation yet remains poorly understood despite decades of research.

THE PROBLEM: Systematic examination of recent comprehensive reviews reveals a dual diversity failure. Brain diversity is underexamined: fatigue, fundamentally a central nervous system symptom, is assessed predominantly through questionnaires (95%-100% of studies) and peripheral biomarkers, while functional neuroimaging appears in fewer than 15% of studies. Population diversity is neglected: reviews consistently document a predominance of Western European and North American cohorts, with racial and ethnic composition inconsistently reported and demographic stratification virtually absent.

THE SOLUTION: Identical fatigue scores reflect heterogeneous brain mechanisms, basal ganglia hypometabolism, frontal dysfunction, inflammatory network disruption, and differentially distributed across populations. Five testable predictions distinguish this framework: (1) neuroimaging reveals distinct subtypes; (2) subtypes show different clinical phenotypes; (3) treatment responses vary by subtype; (4) populations differ in subtype distribution; and (5) stratification resolves apparently inconsistent findings.

RECOMMENDATIONS: Fatigue rehabilitation research should (1) incorporate multimodal neuroimaging as standard, with a tiered protocol accommodating participant burden; (2) intentionally recruit demographically diverse populations; (3) employ data-driven clustering to identify brain-based subtypes; and (4) conduct mechanism-stratified treatment trials. An illustrative study design incorporating multimodal neuroimaging, comprehensive clinical and biological assessment, and diverse population sampling can test core predictions within existing research infrastructure.

IMPACT: Mechanism-based patient stratification enables precision rehabilitation, reducing required trial sample sizes while identifying effective interventions and preventing harm in vulnerable subgroups.

RevDate: 2026-08-28

Adebisi YA, AA Alhur (2026)

Cigarette smoking history, e-cigarette use, and Long COVID: a population-based analysis.

Internal and emergency medicine [Epub ahead of print].

Long COVID imposes a substantial public health burden following the SARS-CoV-2 pandemic, yet the contribution of electronic cigarette (e-cigarette) use, alone or alongside cigarette smoking, remains inadequately characterized in population-representative data. We conducted a cross-sectional analysis of 9274 adults aged 16 years and older from the pooled 2023-2024 Scottish Health Survey, a nationally representative household survey. Cigarette smoking and e-cigarette use were classified into seven mutually exclusive categories, and the outcome was survey-defined self-reported Long COVID, based on symptoms persisting for more than four weeks after first having COVID-19. Survey-weighted logistic regression was used to estimate crude and adjusted odds ratios, with adjustment for survey year, age group, sex, area deprivation, ethnicity, alcohol use, and educational attainment. Overall, 7.4% of adults reported Long COVID. Compared with never cigarette/e-cigarette users, adjusted odds were higher among former cigarette smokers currently using neither product (adjusted odds ratio 1.40, 95% confidence interval 1.12-1.76) and among former smokers currently using e-cigarettes exclusively (1.56, 1.09-2.24). No statistically detectable associations were observed among former e-cigarette users who had never smoked, current e-cigarette users who had never smoked, exclusive current cigarette smokers, or dual users. The two elevated associations persisted after additional adjustment for asthma, chronic obstructive pulmonary disease, diabetes, and cardiovascular disease. The observed pattern may reflect previous cigarette exposure, health-related smoking cessation or switching, reverse causation, and residual selection or confounding; the cross-sectional design does not permit an independent contribution of e-cigarette use to be determined.

RevDate: 2026-08-28
CmpDate: 2026-08-28

Naddeo N, G Faraci (2026)

From Infection Control to Healthcare System Resilience: Lessons Learned from SARS-CoV-2 Research in Healthcare Workers.

La Clinica terapeutica, 177(5):1234-1237.

The COVID-19 pandemic placed unprecedented pressure on healthcare systems and exposed healthcare workers (HCWs) to biological hazards, organizational pressures, and psychological strain. Evidence generated during the emergency shows that HCW protection cannot rely on isolated measures, but requires an integrated framework combining epidemiological surveillance, contact tracing, infection prevention and control, vaccination, occupational health, and workforce support. Contact tracing helped identify occupational exposures and clarify how duration, proximity, and inadequate use of personal protective equipment jointly shaped infection risk. Subsequent studies of reinfection showed that susceptibility reflected the interaction of viral circulation, individual immunity, and vaccination status. Vaccination reduced the clinical impact of SARS-CoV-2 and supported service continuity, although uptake depended on trust, communication, and management of adverse event concerns. The pandemic also highlighted substantial economic consequences and a high burden of psychological distress and burnout among HCWs. Building on this evidence, future preparedness should translate these lessons into permanent, adaptable infrastructure rather than temporary emergency arrangements, integrating interoperable, AI-assisted surveillance capable of combining occupational, diagnostic, vaccination, and genomic data to detect emerging risks early, while ensuring robust data governance and human oversight. Equally central is the need to address long-term workforce vulnerabilities, including Long COVID, attrition, and burnout, through early identification, rehabilitation, flexible return-to-work models, and sustained psychosocial support. Achieving this requires structured multidisciplinary collaboration among occupational medicine, infection control, epidemiology, mental health, and digital health specialists, moving from fragmented infection-control protocols to an integrated, proactive, and learning-oriented preparedness strategy. Protecting HCWs is therefore not only an occupational safety priority but a foundational prerequisite for safe, equitable, and sustainable healthcare delivery during future infectious threats.

RevDate: 2026-08-28

Yuan D, Li S, Zhang R, et al (2026)

A distinct effector B cell population drives autoantibody production in SARS-CoV-2 infection.

Immunity pii:S1074-7613(26)00324-9 [Epub ahead of print].

Autoantibodies (autoAbs) are linked to mortality and Long COVID, yet their cellular origins remain unclear. We analyzed the INCOV cohort and identified 12 age- and sex-matched participants with varying autoAb abundance and integrated single-cell RNA-seq and ATAC-seq data from B cells, plasma proteomics, proteome-wide autoAb profiling, clinical data, and in vitro assays. AutoAb abundance inversely correlated with neutralizing IgG and declined as infection resolved, paralleling the contraction of atypical memory B cells (AtMs). In vitro, AtMs preferentially differentiated into autoAb-producing antibody-secreting cells upon TLR7/8 stimulation. CD11c[+] AtMs (double-negative 2, DN2s) in autoAb-high individuals exhibited increased TLR7 signaling, oxidative stress, and isotype switching, regulated by transcription factors T-bet and XBP1. Integrated genetic and genomic analyses showed that DN2s had the strongest enrichment for autoimmune trait heritability and inferred regulatory effects of autoimmune risk variants among B cell subsets. These findings identify DN2s as key precursors of autoAb-producing cells during SARS-CoV-2 infection.

RevDate: 2026-08-29
CmpDate: 2026-08-29

García-Alonso N, Izquierdo M, Arasanz H, et al (2026)

Immunological effects of supervised exercise in long COVID in adults: A secondary analysis of a randomized crossover trial.

Physiological reports, 14(17):e71031.

Long COVID (post-acute sequelae of SARS-CoV-2 infection) affects approximately 5%-30% of survivors and is characterized by persistent fatigue, dyspnea, exercise intolerance, and cognitive impairment. We evaluated the immunological effects of supervised exercise in adults with long COVID. In this pre-specified exploratory substudy of the EXER-COVID randomized 2 × 2 crossover trial, participants completed a 6-week supervised exercise program (twice weekly) or usual care before crossing over after a 3-5 day washout. Plasma cytokines (IL-1β, IL-6, IL-10, TNF-α, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, and IP-10/CXCL10) were measured by multiplex immunoassay. Immunophenotyping included 20 CD4[+] and CD8[+] T-cell subsets and five innate immune populations. Treatment effects were estimated using within-period change scores, with multiple testing controlled by the Benjamini-Hochberg procedure (false discovery rate < 5%). Five variables reached nominal significance before correction (two CD8[+] T-cell subsets and IL-1β, IL-10, and MIP-1α), but none remained significant after adjustment. No changes were observed in innate immune populations, and no evidence of carryover was detected. Supervised exercise was not associated with significant immunological changes after correction for multiple comparisons, supporting the short-term immunological safety of moderate-intensity exercise in PESE-negative adults with long COVID (ClinicalTrials.gov: NCT04797871).

RevDate: 2026-08-29
CmpDate: 2026-08-29

Kassymbek S, Abduldayeva A, Safonov N, et al (2026)

Risk factors for post-COVID-19 condition among previously hospitalized COVID-19 patients: a systematic review and meta-analysis.

Frontiers in public health, 14:1911482.

BACKGROUND: Post-COVID-19 condition is a major source of long-term morbidity after SARS-CoV-2 infection. Patients hospitalized for COVID-19 may be at particularly high risk because hospitalization often reflects greater acute disease severity and comorbidity burden. However, evidence on risk factors in previously hospitalized populations remains inconsistent due to differences in outcome definitions, follow-up periods, and analytical approaches. This systematic review and meta-analysis aimed to identify risk factors associated with post-COVID outcomes among patients previously hospitalized for COVID-19.

METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 principles. PubMed/MEDLINE, Scopus, Web of Science Core Collection, and the WHO COVID-19 Global Literature Database were searched for studies published between 1 January 2020 and 24 February 2026. Eligible studies included hospitalized patients with confirmed or probable COVID-19, assessed post-acute outcomes at least 4 weeks after acute infection, hospitalization, recovery, or discharge, and evaluated at least one candidate risk factor. Adjusted effect estimates were prioritized, and random-effects meta-analyses were performed when at least two comparable estimates were available.

RESULTS: Eleven studies were included in the qualitative synthesis, and seven contributed to quantitative meta-analysis. Five risk-factor groups were pooled: female sex, acute disease severity or respiratory support, intensive care unit (ICU) admission, vaccination status, and hypertension. Female sex was associated with higher odds of post-COVID outcomes (OR 1.94, 95% CI 1.60-2.35; I [2] = 6.9%). The strongest association was observed for greater acute disease severity or advanced respiratory support (OR 2.55, 95% CI 1.77-3.68; I [2] = 13.0%). ICU admission (OR 1.88, 95% CI 1.24-2.83), no or incomplete vaccination (OR 1.90, 95% CI 1.33-2.72), and hypertension (OR 1.60, 95% CI 1.16-2.20) were also associated with increased odds. Additional predictors, including obesity, age, smoking, dysgeusia, symptom burden, and neurological or psychiatric comorbidity, were summarized narratively.

CONCLUSION: Among previously hospitalized COVID-19 patients, the most consistent risk factors for post-COVID outcomes were female sex, greater acute disease severity or respiratory support, ICU admission, no or incomplete vaccination, and hypertension. These findings support risk-based post-discharge follow-up, although the evidence remains limited by heterogeneous outcome definitions and the small number of studies available for several risk factors.

RevDate: 2026-08-29
CmpDate: 2026-08-29

Chen Y, Li R, Z Zhang (2026)

A retrospective study on the impact of SARS-CoV-2 infection on cardiopulmonary function in a healthy Chinese cohort: a focus on "long COVID".

Frontiers in medicine, 13:1916898.

OBJECTIVE: This retrospective study aimed to observe the cardiopulmonary function and lingering symptoms in previously healthy individuals with Long COVID using Cardiopulmonary Exercise Testing (CPET), the gold standard for evaluating integrated human physiological function.

METHODS: A retrospective analysis was conducted on 73 subjects who completed CPET at Beijing Hospital of Traditional Chinese Medicine from January 2023 to April 2023. Participants were consecutively included and comprised 42 patients with confirmed SARS-CoV-2 infection and persistent symptoms (Long COVID group) and 31 healthy controls with no history of COVID-19 (Normal control group). The sample size was determined by the total number of eligible patients who consecutively underwent CPET during the study period, and a post-hoc power analysis confirmed sufficient power (>80%) to detect the observed differences in the primary endpoint (peak V ˙ O2%pred). General clinical data and CPET parameters were retrospectively collected and compared between the two groups. The chi-square test was used for sex distribution, the independent t-test IS for normally distributed continuous variables, and the Mann-Whitney U test for non-normally distributed variables. Linear regression analysis was performed to explore correlations between peak oxygen uptake (peak V ˙ O2) and other core CPET indicators.

RESULTS: There were 13 males and 18 females in the normal control group and12 males and 30 females in the Long COVID group. No statistical differences were observed in age, sex, height, or weight between the two groups (p > 0.05 for all). (2) In the Long COVID group, core CPET indicators were significantly reduced compared to the normal group: peak V ˙ O2 was78.3 ± 20.7% pred; anaerobic threshold (AT) was 77.9 ± 19.6% pred; peak oxygen pulse (peakO₂pulse) was 100.5 (82.4,110.3)% pred; and Oxygen Uptake Efficiency Plateau (OUEP) was 104.6 ± 12.9% pred (all p < 0.05). (3) Other indicators in the Long COVID group also showed significant differences compared to the normal group, including forced vital capacity (FVC) [3.2(2.8,3.8)L], resting heart rate (rest HR) (87.1 ± 9.3 bpm), peak tidal volume (peak VT) [1.4(1.2,1.9)L], Cardiac Power (CP) [3643.8(2868.7,4522.2)], and the slope of oxygen uptake to work rate (ρ V ˙ O2/ρ WR) [9.6(9.0, 10.54)] (all p < 0.05). However, no significant differences were found in maximal voluntary ventilation (MVV) or peak heart rate (peak HR) between the two groups (p > 0.05). (4) In the Long COVID group, peak V ˙ O2 showed a significant positive linear correlation with AT (R [2] = 0.63, p < 0.001), peakO₂pulse (R [2] = 0.92, p < 0.001), and CP (R [2] = 0.44, p < 0.001), but not with ρ V ˙ O2/ρ WR (R [2] = 0.04, p = 0.357). (5) Among the Long COVID group, the most frequently reported persistent symptoms were: decreased exercise endurance (19.1%), palpitations (16.1%), chest tightness and shortness of breath (12.6%), fatigue (16.9%), insomnia (7.8%), anxiety (7.3%), and cough (4.8%).

CONCLUSION: This retrospective analysis confirms that SARS-CoV-2 infection has a significant and not merely short-term impact on the integrated cardiopulmonary and musculoskeletal function. Even after turning negative, individuals exhibit a wide range of symptoms affecting the respiratory, circulatory, and nervous systems. The observed reduction in peak systolic blood pressure, cardiac power, and the ρ V ˙ O2/ρ WR slope, coupled with compensatory resting tachycardia, suggests the possibility of multiple underlying mechanisms, including subclinical myocardial functional impairment, autonomic nervous system dysfunction, and/or peripheral deconditioning. CPET proved to be a safe and valuable tool for objectively evaluating the overall functional limitations in Long COVID patients.

RevDate: 2026-08-28
CmpDate: 2026-08-27

Obeagu EI (2026)

Cytokine-Driven Hyperinflammation in Long COVID: Mechanisms, Biomarkers, Complement Dysregulation, and Emerging Immunotherapies-A Narrative Review.

Health science reports, 9(9):e73082.

BACKGROUND AND AIMS: Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is a multisystem condition characterized by persistent symptoms that continue beyond the acute phase of infection. Growing evidence indicates that sustained immune dysregulation involving cytokine-mediated inflammation, complement activation, endothelial dysfunction, thromboinflammation, and viral antigen persistence contributes to its pathogenesis. This narrative review summarizes current evidence on the mechanisms underlying hyperinflammation in Long COVID, highlights emerging biomarkers, and evaluates evolving immunotherapeutic strategies.

METHODS: A narrative literature search was conducted using PubMed, Scopus, Web of Science, Embase, and Google Scholar for studies published between 2020 and 2026. Priority was given to systematic reviews, meta-analyses, cohort studies, mechanistic investigations, and clinical trials examining immune dysregulation, inflammatory biomarkers, complement pathways, and targeted therapies in long COVID.

RESULTS: Persistent elevation of pro-inflammatory cytokines, including interleukin-6, interleukin-1β, tumor necrosis factor-α, interferon-γ, and interleukin-17, together with activation of the alternative and lectin complement pathways, contributes to endothelial injury, microvascular thrombosis, neuroinflammation, fibrosis, and multisystem dysfunction. Emerging biomarkers include inflammatory cytokines, complement proteins, endothelial activation markers, coagulation indices, and multi-omics signatures that may improve disease stratification and therapeutic monitoring. Investigational therapies include cytokine-targeted biologics, complement inhibitors, Janus kinase inhibitors, mesenchymal stem cell therapy, microbiome-directed interventions, and precision immunotherapy.

CONCLUSION: Long COVID results from complex interactions between persistent inflammation, complement dysregulation, vascular injury, and immune dysfunction. Integrating validated biomarkers with precision immunotherapeutic approaches may improve diagnosis, risk stratification, and individualized management. However, robust prospective studies and randomized clinical trials remain essential to validate these strategies and optimize long-term clinical outcomes.

RevDate: 2026-08-27

Cohen AK, L Bartlett (2026)

Coronavirus Disease 2019 is an Occupational Disease for Teachers: How to Support the Teacher Workforce.

New solutions : a journal of environmental and occupational health policy : NS [Epub ahead of print].

Analyzing a growing body of epidemiological research that considers coronavirus disease 2019 (COVID-19) as an occupational disease situates teaching (eg, pre-kindergarten, elementary, secondary) among the more vulnerable occupations. Teachers have experienced a higher risk of COVID-19 infection, hospitalization, death, and Long COVID than people from many other occupations. More research attending to occupational patterns and risk mitigation is needed. Taking an occupational epidemiology approach for teachers can inform a wide array of policy solutions, including school environment improvements that can support infection control, like air cleaning and ventilation, as well as supporting teachers experiencing disproportionate burdens of COVID-19, including those living with Long COVID.

RevDate: 2026-08-27

Metz TD, Sandoval GJ, Allshouse AA, et al (2026)

Pregnancy Outcomes in Individuals With Long COVID.

Obstetrics and gynecology [Epub ahead of print].

OBJECTIVE: To evaluate whether there is an association between a maternal classification of Long COVID and adverse pregnancy outcomes.

METHODS: RECOVER (Researching COVID to Enhance Recovery)-Adult is a multicenter prospective longitudinal cohort study of adults with and without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection enrolled from October 2021 to January 2024. This analysis included participants with a SARS-CoV-2 infection and at least one symptom survey for classification of Long COVID status recorded before or during pregnancy. Participants were classified as either likely having Long COVID (LCRI [Long COVID Research Index] score of 11 or higher) or as having Long COVID-indeterminate (LCRI score 0-10), with comparisons made between groups. The primary outcome was preterm birth before 37 weeks of gestation. Secondary outcomes included hypertensive disorders of pregnancy, cesarean delivery, neonatal intensive care admission, and small-for-gestational-age birth weight (below the 10th percentile). Propensity score methods with full matching were used to balance differences in baseline characteristics in estimating an average treatment effect, with a sensitivity analysis estimating the average treatment effect among the treated.

RESULTS: Among 603 participants, 118 (19.6%) were classified as likely having Long COVID before or during pregnancy. Participants classified as likely having Long COVID were more likely to have specific adverse social determinants of health (difficulty covering expenses and paying bills, food insecurity, missed care because of cost, medical discrimination) and had higher prepregnancy body mass index (BMI) than those who were classified as having Long COVID-indeterminate. In the primary average treatment effect analysis, there was no association between likely Long COVID and preterm delivery (adjusted outcome rate 8.1% exposed vs 9.6% unexposed, absolute risk reduction [ARR] 0.82, 95% CI, 0.36-1.90) or secondary outcomes. In average treatment effect among the treated sensitivity analyses, likely Long COVID was similarly not associated with preterm delivery (ARR 1.11, 95% CI, 0.60-2.06) but was associated with an increased risk of hypertensive disorders of pregnancy (adjusted outcome rate 39.0% exposed vs 25.9% unexposed, ARR 1.51, 95% CI, 1.12-2.03) but not with other secondary outcomes.

CONCLUSION: A classification of likely Long COVID was not significantly associated with preterm birth or several other adverse pregnancy outcomes. However, the association with hypertensive disorders of pregnancy in the average treatment effect among the treated analysis highlights the need for further research.

RevDate: 2026-08-27

Choudhury A, Burry MJ, Kwon WJ, et al (2026)

Early HHV-6 IgG and IgA responses during acute SARS-CoV-2 infection in relation to long COVID: a multicohort observational study.

EBioMedicine, 131:106455 pii:S2352-3964(26)00339-7 [Epub ahead of print].

BACKGROUND: Long COVID is a heterogeneous condition associated with both early immune responses to SARS-CoV-2 and antibody responses to herpesviruses. However, herpesvirus-directed antibody responses during acute SARS-CoV-2 infection and their relationship to subsequent long COVID remain poorly understood.

METHODS: We developed a multiplex bead-based serologic assay using recurrent, public peptide epitopes spanning all eight human herpesviruses. Antibody responses were profiled in longitudinal samples from acute SARS-CoV-2 infection and in early post-infection samples from participants in the NIH RECOVER observational cohort. IgG, IgA, and IgM responses were analysed using peptide-, virus-, and factor-level approaches.

FINDINGS: During acute SARS-CoV-2 infection, a subset of individuals exhibited increased herpesvirus-directed IgA responses, particularly against beta-herpesviruses, without corresponding increases in IgG or IgM. In RECOVER participants, subsequent long COVID was associated with herpesvirus- and isotype-specific enrichment of high responders, most prominently HHV-6 IgA and HHV-1/HHV-2 IgG. Unsupervised factorisation identified distinct HHV-6 IgG- and IgA-dominant antibody programs with differing clinical and demographic associations. HHV-6 IgG responses were associated with lower symptom burden and relative enrichment among participants without long COVID, whereas HHV-6 IgA responses were associated with greater symptom burden. HHV-6 IgG responses also declined with increasing age, with the association more readily detected among females.

INTERPRETATION: Early herpesvirus-directed antibody responses following SARS-CoV-2 infection exhibit distinct virus- and isotype-specific patterns associated with long COVID. These findings suggest that heterogeneity in long COVID may be linked to differential herpesvirus-directed humoural immune responses that emerge early after infection.

FUNDING: This study was funded by Stanford Post-Acute Recovery Cohort; NIH and RECOVER grants; the Henry Gustav Floren Family Trust; the Stanford Department of Medicine Team Science Program; Stanford Institutes of Medicine Summer Research Program (SIMR); the Doris Duke Charitable Foundation; the SPARK Program; Nucleate Dojo; the Jessica Lynn Saal Memorial Award; the William and Marissa Rastetter Research Scholar Fund through the Robinson Life Sciences, Business, and Entrepreneurship Program; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health Award.

RevDate: 2026-08-28
CmpDate: 2026-08-28

Vuono R, Allinson KSJ, Zipeto D, et al (2026)

Editorial: Unraveling the long-term effects of COVID-19.

Frontiers in cellular neuroscience, 20:1926660.

RevDate: 2026-08-28
CmpDate: 2026-08-28

Gustavson AM, Woodward-Abel AB, Eaton TL, et al (2026)

Confronting Uncertainty and Addressing Urgency for Action Through the Establishment of a VA Long COVID Practice-Based Research Network.

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 43(1):15-21.

BACKGROUND: Learning health systems (LHS) show promise in making sense of uncertainty and emerging evidence in complex conditions. Long COVID challenges how care is delivered. The Veterans Health Administration has funded a Long COVID Practice-Based Research Network (LC-PBRN) to create an LHS-based infrastructure to promote interdisciplinary collaboration (eg, multidisciplinary clinicians, researchers, operational partners, policymakers, and intra-agency workgroups).

OBSERVATIONS: This article describes the LC-PBRN model, outlines associated lessons learned, and provides suggestions to assist with future PBRN implementations. Lessons learned include incorporating veterans' voices to ensure network efforts align with patient needs, developing an interdisciplinary leadership team to foster diverse viewpoints, setting clear expectations and goals with partners, and building engaging relationships to bridge gaps between internal and external partners.

CONCLUSIONS: The LC-PBRN experience can inform the evolving role of other PBRNs as an integral part of building and sustaining LHS infrastructure.

RevDate: 2026-08-28
CmpDate: 2026-08-28

Ali M, Brady MC, Campbell P, et al (2026)

Individual Participant Data Meta-Analysis (IPDMA) of long-term COVID-19 outcomes in a systematic review-informed, international, multidisciplinary database.

Health and social care delivery research, 14(29):1-160.

BACKGROUND: Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority.

OBJECTIVES: To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs.

DESIGN: Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19.

SETTING: Contributed data were collected in clinical, community and research settings.

INTERVENTIONS: Interventions from original studies were included as covariates in models.

DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo[®] (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019-November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers.

METHODS: Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3-6 months, 9-12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I[2].

OUTCOME MEASURES: Included overall perception of health, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder, fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life.

RESULTS: PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants' median age was 58 years interquartile range (45-68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality.

LIMITATIONS: Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system.

CONCLUSIONS: PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities.

FUTURE WORK: Evidence gaps included healthcare resource use, isolation, loneliness, societal participation and return to work outcomes. Data are needed on the role of health inequity on long-term outcomes.

STUDY REGISTRATION: This study is registered as PROSPERO (CRD42020224323, IRAS ID: 293578).

FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132895) and is published in full in Health and Social Care Delivery Research; Vol. 14, No. 29. See the NIHR Funding and Awards website for further award information.

RevDate: 2026-08-27
CmpDate: 2026-08-26

Siedlecki KL, V Kobrinsky (2026)

The Impact of Long COVID on Cognitive Functioning.

Journal of Intelligence, 14(8):.

This study systematically examined whether long COVID negatively impacts subjective and objective measures of cognition in a community-based sample of 251 participants. Participants completed a battery of neurocognitive tasks (including assessments of short-term memory, working memory, episodic memory, processing speed, executive functioning, and reasoning) and provided self-ratings of their cognition (mental fatigue and subjective cognitive difficulties), depressive symptoms, the impact of symptoms on their life, and completed surveys assessing other psychosocial outcomes. Subgroups included individuals with no known lifetime history of COVID-19 illness (n = 66), those who had recovered from a short-term COVID infection (n = 119), and those who had been diagnosed with long COVID (n = 62). Analyses indicated that long COVID was associated with worse performance on measures of processing speed and executive functioning. In addition, those with a history of long COVID reported higher levels of mental fatigue and subjective cognitive difficulties compared to the other subgroups. Analyses within the long COVID subsample indicated that after controlling for covariates, depressive symptoms were significantly associated with mental fatigue and self-reported cognitive difficulties, and ratings of symptom impact also significantly predicted mental fatigue. These findings reinforce the value of incorporating both subjective and objective assessments when evaluating cognitive outcomes in long COVID, as each captures distinct aspects of functioning. Furthermore, these findings underscore the importance of assessing subjective cognitive concerns and functional symptom burden in clinical encounters, even when objective performance is generally unimpaired.

RevDate: 2026-08-26
CmpDate: 2026-08-26

Theologou M, Kyriakongonas P, Syrmos N, et al (2026)

Treatment and Diagnostic Challenges in a Patient with Atypical SARS-CoV-2-Associated Encephalitis Mimicking a Neoplasm: A Case Report.

Reports (MDPI), 9(3):.

Background and Clinical Significance: Encephalitis is a rare neurological complication associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. In rare cases, focal neuroinflammation can manifest as a mass-like parenchymal lesion, creating profound diagnostic and treatment dilemmas by mimicking primary central nervous system neoplasms. Case Presentation: A 34-year-old female presented with cephalalgia, nausea, confusion, facial palsy, and a new onset of focal impaired awareness seizures (FIAS). Brain magnetic resonance imaging (MRI) revealed a prominent hyperintense lesion within the left temporal lobe with associated vasogenic edema and focal leptomeningeal enhancement highly suspicious of a low-grade glial neoplasm. Although nasopharyngeal RT-PCT was negative, the presence of serum anti-SARS-CoV-2 IgM and IgG suggested recent subclinical SARS-CoV-2 infection. To resolve diagnostic ambiguity and avoid empiric oncological overtreatment, a stereotactic brain biopsy was performed. Histopathology revealed acute neuroinflammation characterized by reactive gliosis, microglial hyperplasia, and perivascular lymphatic cuffing, with no evidence of neoplastic presence. Quantitative tissue RT-PCR confirmed the presence of SARS-CoV-2 (Ct33). Follow-up imaging demonstrated complete resolution of the abnormalities following conservative treatment with corticosteroids and antiepileptics, though mild clinical symptoms persisted for 12 months thereafter. Conclusions: Encephalitis presents a rare yet critical manifestation of SARS-CoV-2. Establishing definitive etiology remains challenging. Stereotactic biopsy is a valuable tool to guide appropriate treatment in cases of ambiguous imaging and clinical findings. Radiographic resolution may precede complete clinical recovery.

RevDate: 2026-08-26

Zahiriharsini A, Ho C, KP Manhas (2026)

Response to the Letter to the Editor: Comment on Effectiveness and Economic Impact of Medical and Rehabilitation Interventions in Long COVID Care.

RevDate: 2026-08-27
CmpDate: 2026-08-26

Charlton BT, Slaghekke A, Appelman B, et al (2026)

Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest.

Nature communications, 17(1):.

Patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suffer from post-exertional malaise. The accompanying physical inactivity may contribute to a lower aerobic capacity and may explain skeletal muscle adaptations in these patients. Here, we compare whole-body exercise responses and skeletal muscle adaptations after strict 60-day bed rest in healthy people with those in long COVID and ME/CFS patients, and healthy age- and sex-matched controls. Bed rest alters respiratory and cardiovascular responses to maximal exercise, which are dissimilar in patients. Bed rest causes muscle atrophy without altering fiber type. Both patient groups have more glycolytic fibers, and ME/CFS patients display type I-specific atrophy. Only after bed rest is oxidative phosphorylation capacity associated with maximal oxygen uptake. As skeletal muscle characteristics differ between patients and healthy individuals after bed rest, physical inactivity cannot solely explain the lower exercise capacity and skeletal muscle adaptations in long COVID and ME/CFS patients.

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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.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )