@article {pmid42471806,
year = {2026},
author = {Girotra, S and Thankachen, SS and Devasenapathy, N and Dutta, M and Bassi, A and Jha, V},
title = {Measuring the carbon footprint of Colchicine for Long COVID - a multicenter trial from India.},
journal = {The journal of climate change and health},
volume = {30},
number = {},
pages = {100706},
pmid = {42471806},
issn = {2667-2782},
abstract = {INTRODUCTION: Reducing greenhouse gas (GHG) emissions from human activities is essential to combat climate change. The healthcare sector contributes to global emissions, and clinical trials play a crucial role in informing evidence-based healthcare practices. Attempts have been made to quantify emissions resulting from clinical trials to help devise effective mitigation strategies. We report carbon emissions from a multicenter clinical trial conducted in both community and hospital settings in India.<br><br>METHODS: We audited the carbon emissions of a multicenter, placebo-controlled trial evaluating the efficacy of colchicine for Long COVID (CTRI/2021/11/038234) using the GHG Protocol Corporate Accounting and Reporting Standard and the Corporate Value Chain Standard. A three-step methodology was followed, including identification of relevant organisational stakeholders and setting the scope of the calculation, data collection by developing relevant study tools, and calculation of emissions using applicable emission factors.<br><br>RESULTS: The total emissions related to the trial were 12.38 tonnes of CO2 equivalents (CO2e) for the trial duration of three years. The top contributors to the emissions were the local commute of trial coordinators and research staff (71%, 8.73 tonnes CO2e), trial meetings (9%, 1.13 tonnes CO2e), patient investigations (10%, 1.27 tonnes CO2e) and the electricity consumption at the clinical trial unit (5%, 0.61 tonnes CO2e).<br><br>CONCLUSION: The study demonstrated the feasibility of assessing the carbon footprint of a clinical trial conducted in India and provides a framework for future assessments and recommendations that can be considered during the planning and implementation of clinical trials.},
}
@article {pmid42471918,
year = {2026},
author = {Cheung, N},
title = {DNA Methylation at Core N-Methyl-D-Aspartate (NMDA) Receptor Genes Reveals a Glutamatergic Signature of Aging in Post-COVID Whole Blood With Implications for Long-COVID Neuropsychiatric Sequelae.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e112902},
pmid = {42471918},
issn = {2168-8184},
abstract = {Background Cognitive symptoms after SARS-CoV-2 infection, often described as "brain fog," remain difficult to measure objectively and are biologically heterogeneous. DNA methylation may provide a stable, blood-accessible layer of information linking post-COVID immune remodeling, biological aging, and neuropsychiatric vulnerability. We re-analyzed GSE247869, a whole-blood Illumina MethylationEPIC dataset from individuals sampled six months after COVID-19 infection, to identify age-associated methylation signals with translational relevance. The present analysis was designed to characterize age-associated methylation within this post-COVID cohort, not to establish a COVID-19-specific signature or biological age acceleration. Methodology This was a cross-sectional analysis of a single post-COVID cohort, with 94 samples included in the age models and no COVID-19-negative comparator included in the analyzed model. Processed beta values were aligned to metadata, converted to M-values, and modeled at each cytosine-phosphate-guanine (CpG) using ordinary least squares with age and sex as predictors. Differentially methylated positions were corrected by Benjamini-Hochberg false discovery rate (FDR). CpGs were mapped to genes using robust annotation and Illumina manifest fallback. Gene-level signals were integrated using a multi-evidence prioritization score that incorporated statistical strength, effect size, multi-CpG support, direction consistency, known epigenetic-clock membership, and curated pathway membership. Results Within this cohort, the analysis identified 3,467 age-associated CpGs at FDR < 0.05, with an overall hypomethylation bias but focal hypermethylation at canonical aging loci. In total, 11 of 12 reference clock CpGs were recovered, including ELOVL2, FHL2, TRIM59, EDARADD, ASPA, and PDE4C. The strongest exploratory signal was enrichment of glutamatergic/N-methyl-D-aspartate (NMDA) genes, including GRIN1, GRIN2C, GRIN2D, GRM1, GRM5, and SLC17A7. GRIN1 and GRIN2C had high integrated evidence scores and showed age-associated hypermethylation. The prioritized genes mapped interpretively to glutamatergic synapse, calcium signaling, and cAMP signaling pathways, although these complete KEGG pathways were not tested as formal enrichment categories. Conclusions This re-analysis recovered established age-associated CpGs and identified age-associated methylation enrichment near glutamatergic/NMDA genes within this post-COVID cohort. It cannot determine whether these signals are specific to COVID-19 infection, reflect accelerated biological aging, or relate to cognitive symptoms because no COVID-19-negative comparator or symptom-level cognitive phenotyping was included in the present analysis. The glutamatergic finding is hypothesis-generating, particularly because the curated set was small and no independent replication cohort was analyzed. Future longitudinal and case-control studies integrating GRIN1/GRIN2C methylation with cognitive and inflammatory phenotyping are needed. Glutamatergic and calcium-signaling pathways may be evaluated in appropriately designed mechanistic and intervention studies, including but not limited to hypotheses related to the Cheung Glutamatergic Regimen, only after independent validation and careful safety evaluation.},
}
@article {pmid42466423,
year = {2026},
author = {Berry, J and Gander, JC and Lu, J and Aguilar, FAA and Teunis, L and Ryerson, AB and de Ramirez, S and Donohue, SE and Mehta, C and Han, JE and Cribbs, SK and Walker, TA and Joseph, Y and Pemu, P and Marconi, VC and Wiley, Z and Verduzco-Gutierrez, M and Bassett, IV and Sharareh, N and Ofotokun, I and Edmiston, M and Javia, V and Elchommali, J and Ifejika, C and Brown-Smith, K and Asencios, W and Elsey, I and Sader, S and Hafner, JW and Hendrickson, M and Kelly, SW and Parthasarathy, S and Pogreba-Brown, K and Nunes, P and Castro, L and Stein-Seroussi, D and Nguyen, K and Saldino, R and Linton, J and Riddick, S and Briscoe, J and Krishnan, JA and Gerald, LB},
title = {Enrolling and retaining a representative population in the NIH Researching COVID to Enhance Recovery (RECOVER)-Adult Cohort.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42466423},
issn = {2693-5015},
abstract = {BACKGROUND: Vulnerable populations are underrepresented in clinical studies. The design of the national RECOVER-Adult cohort study aimed to over-enroll underrepresented populations to ensure the representation of vulnerable populations in the U.S. We quantify and assess follow-up visit completion among a representative population in the RECOVER-Adult cohort.<br><br>METHODS: Between October 2021 and October 2023, we enrolled adult participants across 16 hub-sites in the U.S. Community outreach was used to gather and incorporate feedback prior to and during study implementation. Recruitment methods included electronic and in-person outreach by individuals trained in diversity, equity, and inclusion at health centers, health departments, and community-based organizations, as well as snowball sampling. Study staff maintained regular contact with participants between study visits via phone, email, and text, and arranged free transportation to support attendance.<br><br>RESULTS: Of the 14,880 adult participants who were enrolled in the RECOVER-Adult Cohort Study, 14,531 participants (mean[SD] age: 47.1[15.5] years, 57.0% Non-Hispanic White, 27.7% Male) completed a baseline visit. Over 85% of participants completed the first four follow-up visits, while over 90% completed a last visit. Across follow-up visits, participants who identified as minoritized groups, younger, LGBTQIA+, had less education, did not speak English, lived in a rural area, and reported a disability were less likely to complete their visits, while older and female participants were more likely to complete them.<br><br>CONCLUSIONS: Our findings indicate that enrollment is more feasible than retaining a sociodemographically-representative study population, highlighting a need for innovative approaches to sustain on-going study participation in the post-pandemic era.},
}
@article {pmid42466696,
year = {2026},
author = {Tanguy, S},
title = {[Long COVID: between a syndromic framework and an etiological imperative].},
journal = {Medecine sciences : M/S},
volume = {42},
number = {6-7},
pages = {640-643},
doi = {10.1051/medsci/2026106},
pmid = {42466696},
issn = {1958-5381},
mesh = {Humans ; COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Pandemics ; *Coronavirus Infections/epidemiology/etiology/diagnosis/virology ; *Pneumonia, Viral/epidemiology/etiology/diagnosis/virology ; *Betacoronavirus/physiology ; },
abstract = {Our response to the article "Long COVID: a long story" by Ilana Löwy aims to reiterate the fundamental principles of the definition of Long COVID, focusing on its viral etiology. It emphasizes that the health crisis linked to SARS-CoV-2 cannot be considered over and calls for consideration of all the chronic and long-term effects of the virus. These elements are essential not only to ensure proper recognition of this condition, but also to promote the medical and scientific advances necessary to reduce the health burden associated with Long COVID.},
}
@article {pmid42467443,
year = {2026},
author = {Anderer, S},
title = {Goal-Focused Rehabilitation May Improve Cognitive Outcomes of Long COVID.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.9479},
pmid = {42467443},
issn = {1538-3598},
}
@article {pmid42462858,
year = {2026},
author = {Petry Moecke, DM and Kwong, EH and Yao, J and Singh, C and Cressman, S and Taylor, C and Camp, PG},
title = {Gaps in Physiotherapy Capacity to Provide Long COVID Rehabilitation Care.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {109041},
doi = {10.1016/j.rmed.2026.109041},
pmid = {42462858},
issn = {1532-3064},
abstract = {RATIONALE: Long COVID is a complex multisystemic condition often associated with persistent cardiorespiratory symptoms. Rehabilitation is key for managing symptoms, but there are questions about the capacity of rehabilitation professionals to provide effective care.<br><br>OBJECTIVE: This study assessed the capacity of physiotherapists (PTs) in British Columbia (BC), Canada, to provide Long COVID rehabilitation care.<br><br>METHODS: A cross-sectional online survey was conducted among registered PTs in BC between March and August 2024. The survey covered demographics, current clinical practice, experience with Long COVID, and professional development needs. Descriptive statistics, content analysis, and the WHO Health System Building Blocks Framework were used.<br><br>RESULTS: A total of 139 PTs completed the survey. Most respondents were women (72%) with a mean of 10 (0-47) years of clinical practice. While 44% had treated Long COVID patients, 69% lacked confidence in assessing and managing the condition. PTs had expertise in musculoskeletal symptoms but limited knowledge in treating other common key Long COVID symptoms such as fatigue (17%) and dyspnea (7%). Nearly half required further training in Long COVID-specific patient education. 45% reported the capacity to accommodate Long COVID patients. However, systemic challenges were identified as barriers to effective rehabilitation, including funding shortages, limited workforce, and fragmented care.<br><br>CONCLUSION: Many physiotherapists have the capacity to accept patients with Long COVID, yet require targeted training in cardiorespiratory care, energy conservation for fatigue and post-exertional malaise, and mental health support. Standardized pathways and interdisciplinary networks are critical for effective Long COVID rehabilitation.},
}
@article {pmid42463201,
year = {2026},
author = {Byambasuren, O and Atkins, T and Baptista, S and Glasziou, P and Chakraborty, S},
title = {Effect of low-dose naltrexone for long COVID: a systematic review and meta-analysis.},
journal = {BMJ open},
volume = {16},
number = {7},
pages = {e111253},
doi = {10.1136/bmjopen-2025-111253},
pmid = {42463201},
issn = {2044-6055},
mesh = {Humans ; *Naltrexone/administration &amp; dosage/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; *Narcotic Antagonists/administration &amp; dosage/therapeutic use ; Quality of Life ; Fatigue/drug therapy/etiology ; *COVID-19/complications ; SARS-CoV-2 ; },
abstract = {OBJECTIVE: Long covid is a debilitating chronic condition, and the effect of low-dose naltrexone (LDN) on its symptoms is unclear. We aimed to determine the effectiveness of LDN on symptoms of long covid.<br><br>DESIGN: Systematic review and meta-analysis.<br><br>DATA SOURCES: PubMed, Embase and Cochrane Library for published studies; ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) for registered ongoing studies were searched through 5 May 2026.<br><br>ELIGIBILITY CRITERIA: We included randomised controlled trials and pre-post studies of patients with long covid reporting on fatigue, quality of life, cognitive symptoms or function and other long covid symptoms.<br><br>DATA EXTRACTION AND SYNTHESIS: Two independent reviewers used standardised methods to search, screen and select included studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analysis was conducted using random effects models.<br><br>RESULTS: Of 397 titles and abstracts screened, no randomised controlled trials were identified. Four observational pre-post studies from the USA and Ireland (n=155) met inclusion criteria. LDN doses varied from 1 mg/day to 6&#x2009;mg/day. Pooled pre-post analyses showed moderate effects for reducing fatigue (Hedges' g=-0.74; 95%&#x2009;CI -1.11 to -0.37; p<0.001), brain fog (Hedges' g=-0.53; 95%&#x2009;CI -1.01 to -0.05; p=0.03) and improving sleep quality (Hedges' g=-0.60; 95%&#x2009;CI -0.91 to -0.30; p=0.0001), and large effects for pain (Hedges' g=-0.93; 95%&#x2009;CI -1.29 to -0.57; p<0.001) and daily functioning (Hedges' g=-0.93; 95%&#x2009;CI -1.29 to -0.57; p<0.0001) in favour of LDN. Heterogeneity ranged from 0% to 62%. No serious adverse events were reported in the two studies that assessed safety.<br><br>CONCLUSION: Limited evidence from small pre-post studies suggests LDN may improve fatigue, cognition, sleep, pain and functioning in long covid. However, certainty of evidence is low. Well-powered trials are needed to confirm efficacy, determine dosing and duration and identify subgroups most likely to benefit.<br><br>TRIAL REGISTRATION: https://doi.org/10.17605/OSF.IO/C2VKX.},
}
@article {pmid42464173,
year = {2026},
author = {Feiler, MO and Yucel, RM and Dzomba, BJ and Jones, RM},
title = {Investigating respiratory infection as a post-COVID-19 condition using a large passive surveillance cohort from Track PCC.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13994-0},
pmid = {42464173},
issn = {1471-2334},
support = {NU581IP000003//Centers for Disease Control and Prevention, National Center for Immunizations and Respiratory Diseases/ ; },
abstract = {BACKGROUND: This study examined risk factors for post-COVID respiratory infection using data from the Tracking the Burden, Distribution, Impact of Tracking Post-COVID-19 Conditions in Diverse Populations for Children, Adolescents, Adults (Track PCC) passive surveillance cohort.<br><br>METHODS: This retrospective study included adult Temple Health patients in Philadelphia, Pennsylvania with SARS-CoV-2 (COVID-19) infections from March 2020 to December 2022 and &#x2265;&#x2009;90 days follow-up. COVID-19 infection was identified via laboratory testing, billing codes, or clinical documentation. The primary outcome was post-COVID respiratory infection identified by billing codes. Predictors included social, clinical, and COVID-related correlates. Adjusted logistic regression models were used on 17,539 complete cases and multiple imputed datasets (n&#x2009;=&#x2009;45,513) with SuperMICE.<br><br>RESULTS: In complete-case analysis, uninsured coverage, Alpha variant, total comorbidities, and hospitalization were associated with lower odds of respiratory post-COVID conditions (ORs: 0.02-0.99). Dual Medicare/Medicaid and current smokers, increased odds (ORs: 1.33-1.58). Imputed analyses showed consistent results with and additionally observed higher odds of respiratory infection among those with Medicaid and higher number of vaccinations, and lower odds among those of any non-white race, Hispanic ethnicity.<br><br>CONCLUSIONS: Temple Track PCC findings identify high-risk populations and underscore the utility of advanced imputation in surveillance-based research.},
}
@article {pmid42465874,
year = {2026},
author = {Butzin-Dozier, Z and Wang, LC and Ji, Y and Kumar, M and Anzalone, AJ and Hurwitz, E and Patel, RC and Budhihartanto, A and Buse, JB and Johnson, S and Bramante, C and Wong, R},
title = {GLP Medications and Severe Post-COVID-19 Outcomes Among Individuals with Type 2 Diabetes Mellitus.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.03.26357246},
pmid = {42465874},
abstract = {BACKGROUND: Glucagon-like peptide-1 receptor agonist-based therapies (GLP) have recently emerged as promising treatments across a wide range of health conditions. These medications may have protective effects against severe long-term consequences of COVID-19 by promoting weight loss, exerting antihyperglycemic and anti-inflammatory effects, and providing cardiovascular and endothelial protection.<br><br>METHODS: We evaluated electronic health record data from a retrospective cohort of individuals in the National Clinical Cohort Collaborative. We included individuals with type 2 diabetes mellitus and comorbid COVID-19 who were prescribed either GLP (treatment) or a sodium-glucose co-transporter 2 inhibitor (SGLT2i) and subsequently developed acute COVID-19 between October 1, 2021, and April 1, 2023. We compared the 12-month cumulative incidence of mortality and Long COVID (Long COVID diagnosis and probable Long COVID via computational phenotype) between groups. We applied targeted maximum likelihood estimation to compare outcome risks by exposure status, controlling for covariates of interest.<br><br>RESULTS: We analyzed data from 14,215 individuals with COVID-19 and comorbid type 2 diabetes (mean age, 60 years; mean BMI, 37). Compared to SGLT2i, a prescription for GLP medication was associated with a lower risk of mortality (adjusted risk ratio [aRR] 0.71; 95% CI 0.53, 0.95), but not Long COVID diagnosis (aRR 1.01; 95% CI 0.80, 1.27) or probable Long COVID (aRR 0.94; 95% CI 0.88, 1.01).<br><br>CONCLUSIONS: We found that among individuals with type 2 diabetes and comorbid COVID-19, a prescription for GLP vs. SGLT2i medications was associated with a lower risk of mortality, but not Long COVID.},
}
@article {pmid42465882,
year = {2026},
author = {Butzin-Dozier, Z and Ji, Y and Wang, LC and Kumar, M and Anzalone, AJ and Hurwitz, E and Budhihartanto, A and Patel, RC and Hubbard, A and Halpern, J},
title = {SSRI prescription during acute COVID-19 and risk of Long COVID symptoms and conditions among patients with depression.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.06.26357401},
pmid = {42465882},
abstract = {BACKGROUND: Long COVID is a syndrome characterized by symptoms and conditions across all biological systems. This breadth of Long COVID phenotypes impedes efforts to identify the mechanistic pathways of Long COVID. Low serotonin may play a role in long-term sequelae of COVID-19, and selective serotonin reuptake inhibitors (SSRIs) may prevent these sequelae. Evaluation of the relationship between SSRIs and distinct categories of symptoms and conditions associated with Long COVID can highlight the mechanistic pathways that drive these relationships.<br><br>METHODS: We evaluated electronic health record data from a retrospective cohort of patients in the National Clinical Cohort Collaborative with comorbid depression and COVID-19 between October 2021 and February 2024. We estimated the relationship between SSRI prescription (versus no SSRI prescription) during acute COVID-19 and the one-year cumulative incidence of Long COVID-related conditions and symptoms across 14 human phenotype ontology categories. We applied Super Learner and targeted maximum likelihood estimation to estimate risk ratios while adjusting for confounders of interest and correcting for false discoveries from repeated testing.<br><br>RESULTS: We evaluated EHR data from 542,938 patients. We found that patients who were prescribed SSRIs during COVID-19 had a significantly lower risk of symptoms and conditions related to gastrointestinal factors (adjusted risk ratio (aRR) 0.95, 95% CI 0.92, 0.97), general health (aRR 0.91, 95% CI 0.88, 0.95), headaches (aRR 0.96, 95% CI 0.92, 0.99) and skin (aRR 0.92, 95% CI 0.87, 0.98).<br><br>DISCUSSION: We found that the prescription of SSRIs during acute COVID-19 was associated with a significantly lower risk of post-COVID sequelae related to gastrointestinal, headache-related, skin-related, and general symptoms and conditions, compared with no SSRI prescription. These findings highlight the role of serotonin in Long COVID and specific sequelae that may be reduced by SSRIs.},
}
@article {pmid42465953,
year = {2026},
author = {Butzin-Dozier, Z and Wang, LC and Ji, Y and Anzalone, AJ and Olawore, O and Hafen, R and Hurwitz, E and Kumar, M and Patel, RC and Budhihartanto, A and van der Laan, M and Colford, JM and Hubbard, AE and Buse, JB and Johnson, S and Reusch, J and Chan, LE and Moffitt, R and Wong, R and Bramante, C},
title = {Metformin and Severe Post-COVID-19 Outcomes Among Individuals with Diabetes Mellitus.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.06.26357398},
pmid = {42465953},
abstract = {BACKGROUND: Metformin is one of the most commonly prescribed medications for individuals with diabetes and may provide protection against long-term sequelae of COVID-19.<br><br>METHODS: We evaluated a retrospective cohort of individuals in the National Clinical Cohort Collaborative with type 2 diabetes mellitus and COVID-19 who were prescribed metformin or a dipeptidyl peptidase-4 inhibitor (DPP4i) at least 30 days before the onset of acute COVID-19 between October 1, 2021, and November 15, 2023. We compared the 12-month cumulative incidence of Long COVID diagnosis (ICD-10 U09.9: Post COVID-19 condition, unspecified), probable Long COVID (based on a model-derived phenotype), and mortality between individuals prescribed metformin vs. DPP4i. We applied Super Learner and targeted maximum likelihood estimation to obtain risk ratios while adjusting for covariates of interest.<br><br>RESULTS: In our sample of 53,332 individuals with type 2 diabetes and COVID-19, we found that metformin prescription was associated with a lower risk of all-cause mortality after COVID-19 (adjusted risk ratio [aRR] 0.61, 95% CI 0.51, 0.73). We also observed that metformin users, compared to DPP4i users, had a slightly lower risk of probable Long COVID (aRR 0.87, 95% CI 0.81, 0.94) but did not detect a significant relationship with Long COVID diagnosis (aRR 0.90, 95% CI 0.68, 1.20), although we observed similar point estimates across Long COVID outcomes.<br><br>CONCLUSIONS: These findings support the hypothesis that metformin prescription during acute COVID-19 may be associated with lower mortality among adults with diabetes. These analyses also provide modest evidence of a protective association against Long COVID in adults with diabetes, although estimates were imprecise.},
}
@article {pmid42458333,
year = {2026},
author = {Zhang, Y and Mo, D and Cai, Y and Lv, H and Wei, M and Jing, F and Xu, J and Ou, Y and Yuan, Y and Liu, Z and Fang, X and Wu, W and Ma, X and Ma, X},
title = {Association between dietary inflammatory index, empirical dietary inflammatory patterns and the risk of Long COVID: a prospective cohort study.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-28519-2},
pmid = {42458333},
issn = {1471-2458},
support = {CQYC202005003//Chongqing Talents: Exceptional Young Talents Project/ ; cstc2020jcyj-jqX0014//Outstanding Youth Science Fund of Chongqing/ ; 82373643//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Inflammatory responses and immune dysregulation are considered core mechanisms of Long COVID. Given that diet can modulate systemic inflammation, we evaluated the associations between two indices reflecting dietary inflammatory potential-the Dietary Inflammatory Index (DII) and the Empirical Dietary Inflammatory Pattern (EDIP)-and the risk of Long COVID in a prospective cohort of 69,070 participants from the UK Biobank.<br><br>METHOD: The DII and EDIP were calculated and categorized into quartiles based on Dietary information obtained from the Oxford WebQ online system. Outcome information was obtained from hospital admission records (HESIN, ICD-10) linked to the UK Biobank. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Restricted cubic splines were employed to evaluate the nonlinearity.<br><br>RESULTS: After full adjustment, the highest EDIP quartile (most pro-inflammatory) was associated with increased Long COVID risk (HR&#x2009;=&#x2009;1.15, 95% CI: 1.08-1.22, p&#x2009;<&#x2009;0.001), with no significant association for DII. Yet, both indices demonstrated significant associations with risks for specific organ system conditions-particularly affecting the cardiovascular, gastrointestinal, kidney, and mental health systems-among the 10 predefined categories. Both indices showed significant non-linear associations with Long COVID risk (p for nonlinearity&#x2009;<&#x2009;0.05), with a U-shaped pattern for DII and a J-shaped pattern for EDIP.<br><br>CONCLUSION: In this prospective observational study, a pro-inflammatory dietary pattern was associated with a higher risk of Long COVID-related outcomes and multi-organ sequelae. These findings suggest that dietary inflammatory potential may be relevant to post-COVID-19 health and warrant further investigation as a potentially modifiable factor.},
}
@article {pmid42458402,
year = {2026},
author = {Delano, P and Benavides, FG and Serra, C and Ramada, JM and Gea-Velázquez de Castro, MT and Botella Mira, R and Mirabella, IG and Fernandez Escribano, M and Blasco López, M and Muriel, A and Navarro, G and Serrano, R and Palma-Vasquez, C and Vives, A and Utzet, M},
title = {Sex and occupational differences in long COVID prevalence among healthcare workers: a multicentre registry-based study in three Spanish hospitals.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-28415-9},
pmid = {42458402},
issn = {1471-2458},
support = {2023 FI-3 00065//Ag&#xe8;ncia de Gesti&#xf3; d'Ajuts Universitaris i de Recerca/ ; },
abstract = {AIMS: To estimate the prevalence of long COVID identified through hospital registry data and examine associated occupational and demographic factors among healthcare workers (HCWs) in Spain.<br><br>METHODS: A multicentre study was conducted between 2020 and 2023 in three Spanish hospitals (Madrid, n&#x2009;=&#x2009;1; Barcelona, n&#x2009;=&#x2009;2). Long COVID prevalence and 95% confidence intervals (CIs) were estimated overall and by sex, age group, and occupational category. Associations between long COVID and occupational category were assessed using Poisson regression models with robust variance, stratified by sex and hospital, and adjusted by age and occupation.<br><br>RESULTS: Registry data included 8,439 HCWs. Long COVID prevalence ranged from 3.0% to 5.0% and increased with age, with an adjusted prevalence ratio (PR) increase of 3-9% per year. Occupational differences were more pronounced among men. In University Hospital Ramon y Cajal, male nurses (PR 2.56; 95% CI 1.13-5.81) and other HCWs (PR 3.67; 95% CI 1.12-12.08) had higher prevalence compared with physicians. In Hospital Parc Tauli, male nurse assistants (PR 20.33; 95% CI 3.64-113.42) and support staff (PR 8.30; 95% CI 1.46-47.19) showed markedly elevated prevalence, although confidence intervals were wide. Among women, occupational associations were weaker and less consistent. Overall sex differences were modest, but sex modified the association between occupational role and long COVID prevalence.<br><br>CONCLUSIONS: Long COVID affected approximately 3-5% of HCWs across participating hospitals. Occupational differences in long COVID prevalence were observed, although estimates varied across centres. These findings highlight the importance of occupational health surveillance and follow-up strategies that consider both occupational role and potential sex-specific patterns.},
}
@article {pmid42458561,
year = {2026},
author = {Brus, IM and Heemskerk, SCM and Polinder, S and Nieboer, D and Tieleman, P and Biere-Rafi, S and Haagsma, JA},
title = {Health-related quality of life profiles and trajectories of patients with post COVID-19 condition: a latent Markov model.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13690-026-01996-y},
pmid = {42458561},
issn = {0778-7367},
abstract = {BACKGROUND: The aim of this study was to identify subgroups with similar health states based on health-related quality of life (HRQoL) profile (i.e. differences in affected dimensions and severity of problems per dimension) among PCC patients, to examine transitions between these subgroups over time, and to examine the association with sociodemographic and medical characteristics.<br><br>METHODS: In this longitudinal cohort study, data from 5,737 PCC patients, collected through two online surveys, were analysed using a latent Markov model. Dichotomized HRQoL scores per EQ-5D-5L dimension were used as indicators to determine latent states and covariates were added into the model.<br><br>RESULTS: A model with six latent states was selected. The largest state, consisting of 31% of respondents, was characterized by a high probability of problems on all dimensions, whereas the smallest state (7%) was characterized by a low probability of problems on all dimensions, except usual activities. The remaining four states were all characterized by a high probability of problems on usual activities and pain/discomfort, but differed based on the probability of problems on the dimensions mobility, self-care and anxiety/depression. The probability of transitioning to a different state was low, with states with fewer affected dimensions being most stable. Women, younger respondents, those with a lower educational level, and those with comorbidity were more likely to be in states with more affected dimensions.<br><br>CONCLUSIONS: The identification of different HRQoL profiles shows that there is substantial heterogeneity in the HRQoL dimensions that are affected and in observed changes between two measurement points.},
}
@article {pmid42459458,
year = {2026},
author = {Cousins, O and Jokela-Pansini, M and Alwan, NA and Barnard, E and Ceolta-Smith, J and Dainow, J and Dalton, C and Davies, G and Faghy, MA and Gilmour, E and Patel, I and Sherwood, O and Westerhof, L and Greenhough, B},
title = {Correction: Co-creating a social science research agenda for Long Covid.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1748942},
doi = {10.3389/fpubh.2026.1748942},
pmid = {42459458},
issn = {2296-2565},
abstract = {[This corrects the article DOI: 10.3389/fpubh.2025.1654488.].},
}
@article {pmid42460883,
year = {2026},
author = {Ruchisrisarod, C and Kaewpom, T and Wanthong, P and Luechaipanit, W and Bunprakob, S and Ampoot, W and Yomrat, S and Hemachudha, P and Supharatpariyakorn, T and Thanapornsangsuth, P and Tammachote, R and Saraya, AW},
title = {Inflammatory and neuroinjury blood biomarkers across COVID-19 severity groups in individuals with persistent neurological symptoms.},
journal = {International journal of immunopathology and pharmacology},
volume = {40},
number = {},
pages = {3946320261465568},
doi = {10.1177/03946320261465568},
pmid = {42460883},
issn = {2058-7384},
mesh = {Humans ; Biomarkers/blood ; Male ; Female ; *COVID-19/blood/complications/diagnosis ; Middle Aged ; Aged ; *Cytokines/blood ; Case-Control Studies ; Severity of Illness Index ; tau Proteins/blood ; Glial Fibrillary Acidic Protein/blood ; Adult ; *Nervous System Diseases/blood/diagnosis ; Post-Acute COVID-19 Syndrome ; Neurofilament Proteins/blood ; Amyloid beta-Peptides/blood ; *Neuroinflammatory Diseases/blood ; *Inflammation Mediators/blood ; },
abstract = {Persistent neurological symptoms such as cognitive impairment, fatigue, and neuropsychiatric disturbances are increasingly reported in patients with long COVID, with chronic neuroinflammation and neuronal injury proposed as potential contributors. To characterize inflammatory and neuroinjury-related biomarker patterns, we conducted a case-control study including 325 participants recruited at King Chulalongkorn Memorial Hospital between January 2022 and December 2023, comprising 265 individuals with persistent neurological symptoms following COVID-19 infection and 60 asymptomatic COVID-19 participants who did not develop long COVID symptoms. Blood samples were analysed for inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, IFN-α, IL-4) using multiplex immunoassays, and for neuroinflammatory and neurodegenerative biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, and beta-amyloid peptides (Aβ40, Aβ42) using SIMOA and ELISA platforms. Among 265 participants with complete data (critical = 7, severe = 22, moderate = 79, mild = 157), patients with severe and critical COVID-19 exhibited significantly higher concentrations of IL-6, IL-1β, TNF-α, and IL-8, together with elevated NfL, GFAP, and phosphorylated tau181 levels, and reduced Aβ42/40 ratios. Strong positive correlations between neurodegenerative biomarkers and pro-inflammatory cytokines were observed in critically ill patients, whereas these associations were weak or absent in mild and moderate cases. Older age was also associated with greater disease severity and increased risk of persistent neurological complications. These findings indicate that individuals with persistent neurological symptoms following COVID-19, particularly those with a history of severe or critical disease, exhibited higher inflammatory and neuroinjury-related biomarker levels, while blood-based biomarkers such as NfL, GFAP, and phosphorylated tau181 may serve as minimally invasive tools for characterizing neurological involvement and identifying patients at risk of long-term neurological sequelae.},
}
@article {pmid42461564,
year = {2026},
author = {Negron, M and Wang, J and Wang, X and O'Keeffe, LA and Qian, G and Mueller, KT and Saavedra, AA and Davis, NA and Getachew, LS and Sparks, JA and Patel, NJ},
title = {Association of oral outpatient antiviral medications for COVID-19 with the risk of post-acute sequelae of COVID-19 at 28 and 90 days in a cohort of individuals with systemic autoimmune rheumatic diseases.},
journal = {Clinical rheumatology},
volume = {},
number = {},
pages = {},
pmid = {42461564},
issn = {1434-9949},
abstract = {INTRODUCTION/OBJECTIVES: Prior studies have evaluated the relationship between antiviral medications for COVID-19 and the risk of post-acute sequelae of COVID-19 (PASC, i.e., "long COVID") in the general population. We evaluated PASC in individuals with systemic autoimmune rheumatic diseases (SARDs) by antiviral use, hypothesizing that antivirals are associated with lower PASC risk.<br><br>METHODS: We investigated oral outpatient antiviral use (nirmatrelvir/ritonavir or molnupiravir) and PASC in a prospective SARD cohort at Mass General Brigham&#x2009;&#x2265;&#x2009;28&#xa0;days following COVID-19 infection (16/December/2021-30/January/2025). Participants completed surveys regarding symptom duration. We investigated odds of PASC at 28 and 90&#xa0;days following COVID-19 using multivariable logistic regression.<br><br>RESULTS: Among 431 participants (mean age 56.2&#xa0;years, 81% female), 51% were treated with oral antivirals. The most common SARD type was inflammatory arthritis (46%), 46% were using conventional synthetic DMARDs, and 41% were using biologic DMARDs. Nearly all (96%) were vaccinated at the time of COVID-19 infection. Those who received antivirals had similar odds of PASC at 28&#xa0;days (30.9% vs. 31.1%, aOR 0.98, 95% CI: 0.64-1.49) and numerically lower odds at 90&#xa0;days (5.2% vs. 10.5%, aOR 0.44, 95% CI: 0.19-1.02) compared to those who did not receive antivirals.<br><br>CONCLUSION: In this contemporary cohort, risk of PASC 90&#xa0;days after COVID-19 onset was overall low. Those who received antiviral therapy had similar odds of PASC at 28&#xa0;days and numerically lower odds of PASC at 90&#xa0;days compared to those who did not receive antivirals, providing evidence to quantify PASC risk when considering oral outpatient antiviral treatment. Key Points &#x2022; Among people with rheumatic diseases, post-acute sequelae of COVID-19 (PASC) status at 28&#xa0;days after symptom onset was similar regardless of antiviral use. &#x2022; Odds of PASC at 90&#xa0;days were numerically lower with antiviral use. &#x2022; Patient-reported outcomes were similar regardless of antiviral use.},
}
@article {pmid42462688,
year = {2026},
author = {Ammari, T},
title = {Patient-made knowledge networks: Long COVID discourse, epistemic injustice, and online community formation.},
journal = {Social science &amp; medicine (1982)},
volume = {405},
number = {},
pages = {119593},
doi = {10.1016/j.socscimed.2026.119593},
pmid = {42462688},
issn = {1873-5347},
abstract = {Long COVID represents an unprecedented case of patient-led illness definition, emerging through Twitter in May 2020 when patients collectively named and legitimized their condition before medical recognition. This study examines 2.8 million tweets containing #LongCOVID through topic modeling followed by content analysis of a purposively sampled 5100 tweets, and exponential random graph modeling (ERGM) to understand how contested illness communities construct knowledge networks. User roles were identified through analysis of Twitter biography fields and review of 1000 tweets (10 per user) from the 100 highest-centrality accounts. We identify seven discourse themes spanning symptom documentation, medical dismissal, cross-illness solidarity, and policy advocacy, alongside a differentiated ecosystem of four user roles. ERGM results demonstrate that tie formation centers on epistemic practices-knowledge sharing and community building-rather than policy debates, supporting characterization of this space as an epistemic community in Haas's (1992) sense. Long COVID patients achieved World Health Organization (WHO) recognition within months, contrasting sharply with decades-long struggles of similar conditions. These findings illuminate how social media affordances enable marginalized patient populations to construct alternative knowledge systems, form cross-illness coalitions, and contest traditional medical authority.},
}
@article {pmid42462744,
year = {2026},
author = {Oppegaard, O and Blomberg, B and Cox, RJ and Iversen, A and Myklebust, NN and Glambek, M and Tøndel, C and Dahl, TB and Friis, T and Mjøs, E and Lehmann, ME and Sandvig, A and Devold, V and Wilhelmsen, M and Trøseid, M and Lie, RT and Aukrust, P and Langeland, N and , },
title = {Nirmatrelvir for acute COVID-19 to prevent long COVID (PANORAMIC Norway): a double-blind, randomised, placebo-controlled trial.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(26)00244-6},
pmid = {42462744},
issn = {1474-4457},
abstract = {BACKGROUND: Long-term symptoms are common after acute COVID-19, particularly fatigue, cognitive problems, and dyspnoea. Cohort studies have suggested that antiviral treatment of acute COVID-19 might prevent development of post-COVID-19 condition (also known as long COVID), but the efficacy of antivirals has yet to be verified in prospective studies. We aimed to investigate whether treatment of acute SARS-CoV-2 infection with nirmatrelvir-ritonavir would reduce the risk of long COVID.<br><br>METHODS: In this double-blind, randomised, placebo-controlled trial, participants were recruited from the municipal health-care service at three sites in Norway (Bergen, Oslo, and &#xc5;lesund). Non-hospitalised adults aged 18-65 years with SARS-CoV-2 infection confirmed by PCR or lateral flow test and symptoms for 5 days or fewer were eligible for inclusion. Key exclusion criteria included pregnancy or lactation, chronic renal impairment or chronic liver dysfunction, and any person judged by the investigator to need nirmatrelvir-ritonavir treatment due to increased risk of hospitalisation or death. Participants were allocated in a 1:1 ratio to receive oral 300 mg nirmatrelvir and 100 mg ritonavir, or placebo, twice a day for 5 days using a pre-generated randomisation list without stratification or block adjustment. Participants, clinicians, and the study team were masked to treatment allocation. The primary outcome was long COVID, defined as patient-reported fatigue, dyspnoea, and/or cognitive symptoms at 3 months' follow-up. Safety was analysed as a secondary outcome, and included adverse events, hospital admissions, and deaths. Both the primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (NCT05852873) and is now closed to new participants.<br><br>FINDINGS: Between May 12, 2023, and June 11, 2025, we enrolled 144 participants, of whom 66 were assigned to nirmatrelvir-ritonavir and 78 to placebo. In the protocol we planned to enrol 2000 participants, but the trial was stopped prematurely by the steering committee due to insufficient recruitment. Among the 143 participants who completed follow-up, the risk of long COVID at 3 months was significantly reduced in the nirmatrelvir-ritonavir group (17 [26%] of 66) compared with the placebo group (33 [43%] of 77), corresponding to a relative risk after imputation of data for the single missing value in the placebo group of 0&#xb7;60 (95% CI 0&#xb7;37-0&#xb7;98; p=0&#xb7;039). In the nirmatrelvir-ritonavir group, five patients discontinued treatment due to adverse events. The most common adverse events in the nirmatrelvir-ritonavir group were change in taste or smell (57 [86%] of 66 in the nirmatrelvir-ritonavir group vs 14 [18%] of 78 in the placebo group) and nausea or vomiting (19 [29%] vs eight [10%]). Inversely, palpitations were more common in the placebo group (ten [13%] of 78) than in the nirmatrelvir-ritonavir group (two [3%] of 66). No severe adverse events were reported.<br><br>INTERPRETATION: Treatment with nirmatrelvir-ritonavir for acute COVID-19 was associated with a significant reduction in the risk of long COVID at 3 months' follow-up. The limited sample size precludes firm conclusions, and further clinical trials are warranted.<br><br>FUNDING: National Health Authorities' KlinBeForsk programme, Western Norway Regional Health Authority, Helse M&#xf8;re og Romsdal Hospital Trust, and The Influenza Centre, Haukeland University Hospital and University of Bergen, Bergen, Norway.},
}
@article {pmid42462746,
year = {2026},
author = {Kelly, JD and Peluso, MJ},
title = {Towards a long COVID prevention agenda.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(26)00361-0},
pmid = {42462746},
issn = {1474-4457},
}
@article {pmid42447127,
year = {2026},
author = {Bomans, S and Michotte, N and El M'Rabet, I and Jimenez Garcia, B and Leemans, L and Janssens, P and Hanon, S and De Waele, E and Beckwée, D},
title = {Agreement and reliability between the two-day 6-minute incremental step test and two-day cardiopulmonary exercise test in post COVID-19 condition for assessing post-exertional malaise: The REVEAL-study.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0353132},
pmid = {42447127},
issn = {1932-6203},
mesh = {Humans ; Reproducibility of Results ; *Exercise Test/methods ; Cross-Over Studies ; *COVID-19/complications/physiopathology ; Female ; Male ; Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/isolation &amp; purification ; Middle Aged ; Fatigue/physiopathology ; Oxygen Consumption ; Physical Exertion ; },
abstract = {BACKGROUND: Post-Exertional Malaise (PEM) is a core symptom of post COVID-19 condition (also known as long COVID) affecting millions of people, yet assessment remains challenging. The two-day cardiopulmonary exercise test (CPET) is the current gold standard for objectifying PEM, but its cost and patient burden limit use. The two-day 6-minute incremental step test (6MIST) with wireless wearable sensors could offer a more accessible alternative.<br><br>METHODS: This cross-over study (n&#x2009;=&#x2009;25, one-month washout period) evaluated the level of agreement and reliability between the two-day 6MIST and the two-day CPET for assessing PEM. Each "two-day" test consisted of two identical exercise tests separated by 24 hours to capture worsening of symptoms on day 2. Objective (VO2peak) and subjective (fatigue, neuromuscular complaints and rated perceived exertion) PEM outcomes were collected. Subjective outcomes were measured in relation to the first exercise test of each two-day session; at 15 minutes pretest, 15 minutes posttest and 24 hours posttest, with changes analyzed as &#x394;1 (baseline to 15 minutes posttest) and &#x394;2 (15 minutes posttest to 24 hours posttest). Agreement was assessed using Bland-Altman plots and reliability through consistency Intraclass Correlation Coefficients. The study is registered in ClinicalTrials.gov (Ref: NCT06933017).<br><br>RESULTS: VO2peak and neuromuscular complaints showed low agreement and reliability between the two tests. Rated perceived exertion showed moderate reliability at all times and fatigue showed moderate reliability for changes after 24h (&#x394;2).<br><br>CONCLUSIONS: Contrary to our hypothesis, the two-day 6MIST shows limited agreement with the two-day CPET overall. However, moderate reliability for rated perceived exertion and fatigue suggests potential for improvement with protocol refinement. Further research is needed to optimize the two-day 6MIST and to develop assessments that capture PEM both within and beyond the 24-hour period.},
}
@article {pmid42448283,
year = {2026},
author = {Coppens, L and Górska, A and Hotterbeekx, A and Canziani, LM and Mateescu, VO and Gentilotti, E and Pirici, D and Berkell, M and , and Malhotra, S and Taconelli, E and Kumar-Singh, S},
title = {Longitudinal assessment of SARS-CoV-2 Spike and Nucleocapsid antigenemia in the ORCHESTRA Post-COVID cohort.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2026.07.012},
pmid = {42448283},
issn = {1469-0691},
abstract = {OBJECTIVES: Spike antigenemia has been proposed as a mechanism underlying post-COVID condition (PCC). We determined whether persistent free SARS-CoV-2 Spike or Nucleocapsid antigenemia is associated with post-COVID condition (PCC) or systemic inflammation. As a secondary methodological aim, we evaluated whether dithiothreitol (DTT) treatment reliably unmasks antibody-bound Spike.<br><br>METHODS: Within the ORCHESTRA project, we quantified free Spike and Nucleocapsid in 200 participants (112 PCC, 58 non-PCC and 30 pre-pandemic controls), analysing 576 samples collected during acute infection (n=99) and at 3, 6, 12, and 18 months post-infection (n=447). Correlations between free Spike and proinflammatory markers were assessed. The effect of 10 mM DTT on Spike detectability was validated prior to analysis.<br><br>RESULTS: During acute infection, Nucleocapsid was detectable in nearly all participants (n=98/99), and Spike in 15/99 (15.2%). Low-level antigen persisted in a subset of participants up to 18 months, however, neither free Spike nor Nucleocapsid differed between PCC and controls or were independently associated with PCC (Spike: OR, 0.99; 95% CI, 0.55-1.78; Nucleocapsid: OR, 0.52; 95% CI, 0.14-2.03). At 3-6 months post-infection, free Spike correlated with proinflammatory cytokines, with stronger associations in PCC than controls (all p<0.05). Methodologically, DTT reduced recombinant Spike detectability by 90.9&#xb1;0.7% at 10 mM (p<0.001) yet increased measured plasma signal 2.6&#xb1;2.7-fold in pandemic samples and 5.5&#xb1;2.4-fold in pre-pandemic controls (p<0.001), indicating non-specific assay artifact rather than recovery of antibody-bound antigen.<br><br>CONCLUSIONS: Low-level systemic antigen persistence occurs in a subset of individuals but does not differentiate PCC from recovered controls. Early convalescent Spike-cytokine correlations likely reflect transient, host-specific immune activation rather than a persistent viral driver. Furthermore, DTT does not recover true immune-complexed antigen but generates non-specific assay artifacts. These data argue against persistent circulating antigenemia as a primary, generalizable driver of PCC, highlighting the need for cautious biomarker interpretation.},
}
@article {pmid42449996,
year = {2026},
author = {Pesqueira Sanchez, MA and de Necochea Campion, R and Dalhuisen, T and Fehrman, EA and Chhabra, PS and Kelly, JD and Martin, JN and Deeks, SG and Henrich, TJ and Peluso, MJ and LaRosa, SP},
title = {Increased Mannosylation of Extracellular Vesicles in Long COVID Plasma as a Binding Target for Galanthus nivalis Agglutinin (GNA) Affinity Resin.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
doi = {10.3390/ijms27135723},
pmid = {42449996},
issn = {1422-0067},
support = {Not Applicable//Aethlon Medical (United States)/ ; Not Applicable//PolyBio Research Foundation/ ; R01AI141003; R01NS136197; K23AI157875//National Institutes of Health (NIH)/ ; },
mesh = {*Extracellular Vesicles/metabolism ; Humans ; Glycosylation ; MicroRNAs/metabolism/genetics/blood ; *Plant Lectins/metabolism/chemistry ; *COVID-19/blood/metabolism ; Post-Acute COVID-19 Syndrome ; *Mannose/metabolism ; SARS-CoV-2/isolation &amp; purification ; Galanthus/chemistry ; Mannose-Binding Lectins ; },
abstract = {There is no proven therapy for Long COVID, a post-acute condition characterized by persistent symptoms following SARS-CoV-2 infection. Extracellular vesicles (EVs) are emerging as mediators of disease pathogenesis through their molecular cargo. We investigated whether EV glycosylation is altered in Long COVID plasma and whether these vesicles can be selectively targeted using a glycan-binding affinity resin. Large (100-500 nm) and small (40-200 nm) EVs were isolated from post-acute COVID-19 plasma and analyzed by nanoparticle flow cytometry to assess surface glycosylation. Small EV capture assays were performed using Galanthus nivalis agglutinin (GNA) affinity resin. Plasma miRNA profiles before and after GNA treatment were evaluated using NanoString nCounter analysis, and potential downstream pathway effects were computationally inferred using validated miRNA-mRNA interactions and PROGENy. Mannose-positive large EVs were significantly increased in Long COVID compared to recovered controls (p < 0.05). GNA-mediated small EV capture correlated with mannose-positive EV abundance (r = 0.341, p < 0.05), and seven miRNAs were significantly reduced following treatment. Computational pathway analysis suggested modulation of key signaling pathways, including JAK-STAT, Estrogen, VEGF, and PI3K. These findings suggest a glycan-associated EV signature in Long COVID and support further investigation of lectin-based capture as a potential strategy to target vesicle-associated molecular cargo.},
}
@article {pmid42450602,
year = {2026},
author = {Palladini, M and Mazza, MG and Bravi, B and Bessi, M and De Lorenzo, R and Rovere-Querini, P and Benedetti, F},
title = {Sex-Specific Association Between Acute COVID-19 Systemic Inflammation and Persistent White Matter Pathology and Cognition in Survivors.},
journal = {Biology},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/biology15131054},
pmid = {42450602},
issn = {2079-7737},
abstract = {Six years into the COVID-19 pandemic, evidence is increasingly clear that long COVID affects women disproportionately, with higher rates of persistent cognitive and neurological symptoms. Yet, the biological mechanisms underlying this sex-dimorphic impact remain elusive. We investigated whether the immune storm of acute COVID-19 leaves a silent yet sex-specific scar on white matter integrity that shapes long-term cognitive health. In 60 previously hospitalized COVID-19 survivors, we combined an inflammatory snapshot at admission proxied by the systemic immune-inflammation index (SII) with 3T diffusion MRI and a comprehensive cognitive battery (BACS) acquired three months after recovery. Sex reshaped the inflammation-brain relationship: a higher SII predicted a diffuse alteration pattern within core associative and inter-hemispheric fibres in females only, sparing the male architecture despite a comparable inflammatory burden. In women, white matter damage coupled with poorer psychomotor coordination, and mean diffusivity fully mediated the link, unveiling a female-specific pathway from systemic inflammation to cognitive slowdown. COVID-19 inflammation imprints a durable, sex-sensitive footprint on white matter that selectively undermines psychomotor coordination in female survivors, despite a clinical recovery. This work positions women's white matter as a critical target of post-COVID neuroinflammation and argues for sex-informed monitoring and interventions that explicitly tackle immune-brain crosstalk in long COVID.},
}
@article {pmid42451144,
year = {2026},
author = {Navarro-Cáceres, A and Navarro-Matías, E and Arroyo-Romero, S and Suárez-Moreno, N and Domínguez-Martín, A and Lugones-Sanchez, C and Gonzalez-Sanchez, S and Gómez-Marcos, MA and Gómez-Sánchez, M and Gómez-Sánchez, L and BioICOPER Investigators Group, },
title = {Dietary Mineral Intake and Vascular Health in Patients with Long COVID-19: The BioICOPER Study.},
journal = {Nutrients},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/nu18132140},
pmid = {42451144},
issn = {2072-6643},
support = {PI25/00071//Instituto de Salud Carlos III/ ; IBYAP23_00001//Instituto de Investigaci&#xf3;n Biom&#xe9;dica de Salamanca/ ; GRS 2976/C/2024, GRS 3007/C/2024, GRS 2714/C/2023, and GRS 2501/B/22//Junta of Castile and Le&#xf3;n/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/complications ; Vascular Health ; *Vascular Stiffness ; Middle Aged ; Pulse Wave Analysis ; Aged ; *Minerals/administration &amp; dosage ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Carotid Intima-Media Thickness ; *Diet ; Carotid-Femoral Pulse Wave Velocity ; Ankle Brachial Index ; },
abstract = {Background/Objectives: Long COVID-19 (LC) has been associated with persistent inflammation and impaired vascular health. Dietary minerals are involved in oxidative stress, endothelial homeostasis, and arterial stiffness; however, their relationship with vascular health in LC remains poorly explored. This study aimed to examine the association between energy-adjusted dietary mineral intake and markers of vascular stiffness and vascular aging in adults with LC, while exploring potential sex-specific patterns. Methods: A total of 304 adults with LC from the BioICOPER study were included. Dietary mineral intake was assessed using a validated 7-day dietary record from the EVIDENT tool and expressed as mineral density per 1000 kcal for the regression analyses. Vascular assessment included carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity (baPWV), and the vascular aging index (VAI). Hierarchical multivariable linear regression models, false discovery rate (FDR) correction, restricted cubic spline analyses, sensitivity analyses excluding supplement users, and formal sex × mineral interaction tests were performed. Results: In descriptive adequacy analyses, adequate iron intake was associated with lower baPWV. In energy-adjusted linear regression models, no mineral-outcome association remained statistically significant after FDR correction. In the fully adjusted sensitivity model, zinc density showed a nominal positive association with cfPWV, but this association did not survive FDR correction. Restricted cubic spline analyses suggested possible non-linear associations of magnesium and potassium density with cfPWV and VAI. Formal interaction analyses did not provide robust evidence of sex-related effect modification. Conclusions: After energy adjustment and correction for multiple testing, the evidence for independent linear associations between dietary mineral density and vascular outcomes in adults with LC was limited. These exploratory findings suggest that mineral intake, dietary sources, and non-linear patterns deserve further evaluation in prospective studies and nutritional intervention trials.},
}
@article {pmid42452430,
year = {2026},
author = {Munzir, SI and Hier, DB and Carrithers, MD},
title = {Distinct Regulatory DNA Methylation Signatures Across Multiple Sclerosis, Neuromyelitis Optica, and Neurological Post-Acute Sequelae of COVID-19.},
journal = {Journal of clinical medicine},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/jcm15134968},
pmid = {42452430},
issn = {2077-0383},
support = {n/a//University of Illinois Chancellor's Fund/ ; n/a//Wershkoff Endowment for Multiple Sclerosis Research/ ; },
abstract = {Background/Objectives: Our prior epigenome-wide association study (EWAS) on multiple sclerosis (MS) identified myeloid-associated methylation signatures and an association with enhancer regions. Here we compared differential DNA methylation across three central nervous system inflammatory disorders: MS, neuromyelitis optica (NMO), and neurologic post-acute sequelae of COVID-19 (neuro-PASC). Methods: Whole-blood DNA was profiled on Infinium MethylationEPIC arrays. Analyses included EWAS at the CpG level, differentially methylation region (DMR) analysis, and gene regulatory-element enrichment using Locus Overlap Analysis (LOLA). Limma linear models were adjusted for race, EPIC array version, age, sex, disease-modifying treatment class, and blood cell composition. Results: All three diseases were associated with broad CpG-level differential methylation. The most robust findings were disease-specific DMR signatures in gene regulatory regions. All three diseases shared Lamin B1-anchored chromatin states as an architectural genomic feature but differed in immune regulatory transcription factor binding sites (TFBS), RNA polymerase (Pol II) occupancy, and DNase accessibility. MS was enriched for TFBS in myeloid CEBPB and SPI1/PU.1 and lymphocyte-associated RUNX3, EBF1, and BATF. MS hypomethylated DMRs were concentrated at active enhancers and myeloid TFBS, suggestive of chronic myeloid activation. NMO showed the clearest promoter and B lymphocyte associated profile. Neuro-PASC was associated with hematopoietic DNase accessibility and TFBS for BATF and EBF1. Conclusions: These results suggest that DNA methylation in MS, NMO, and neuro-PASC differ meaningfully in regulatory architecture rather than conforming to a single shared disease-associated methylation model. A long-term goal is to develop immune therapies for newly recognized diseases such as neuro-PASC.},
}
@article {pmid42452662,
year = {2026},
author = {Değer, M and Kılıç, T and Ulutaş, Z and Tan, MS and Ödümlü, H and Atila, A and Demir, HB and Soysaldı, B and Karaağaç, M and Er, YE and Akdağ, O},
title = {Three- and Nine-Month Follow-Up of Patients with COVID-19: Clinical, Functional, and Radiological Outcomes.},
journal = {Journal of clinical medicine},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/jcm15135202},
pmid = {42452662},
issn = {2077-0383},
abstract = {Background/Objectives: The acute complications of COVID-19 have been well characterized and are frequently associated with increased mortality. Although substantial knowledge regarding long COVID has accumulated since the beginning of the pandemic, important uncertainties remain regarding the long-term clinical, functional, radiological, and metabolic consequences of SARS-CoV-2 infection. Identification of post-COVID-19 complications is therefore essential for appropriate recognition and management. This study aimed to evaluate the long-term complications of COVID-19 at 3 and 9 months after infection. Methods: This prospective study was conducted at Inonu University Turgut Ozal Medical Center. Patients who presented with active post-COVID-19 complaints or for routine follow-up were enrolled. Participants were evaluated at the pulmonology outpatient clinic at 3 and 9 months. At each visit, persistent or new-onset symptoms were assessed, and pulmonary function tests (PFT), the six-minute walk test (6MWT), echocardiography (ECHO), and thoracic computed tomography (CT) were performed as clinically indicated. Patients were stratified into three groups according to the severity of acute illness: outpatient, ward-hospitalized, and ICU-hospitalized. Results: A total of 205 patients (120 male, 85 female) were included. Male patients had significantly higher rates of ward and ICU hospitalization than female patients (p = 0.006). At 9 months, 85.3% of patients had at least one persistent symptom; dyspnea (69.6%), cough (35.6%), and chest pain (32.5%) were the most common. FVC showed a statistically significant increase between months 3 and 9 (p = 0.014), and the 6MWT distance improved significantly (423.56 m vs. 464.10 m; p = 0.008). Ground-glass opacity, present in 90.2% of patients at admission, persisted in 44.3% at 9 months (p < 0.001). Reticular opacities, pleuroparenchymal bands, and mosaic perfusion patterns increased over time. ICU patients had significantly lower ejection fraction values compared with ward and outpatient groups at 9 months (p = 0.046). During follow-up, 13 patients developed pulmonary embolism and 7 developed new-onset diabetes mellitus. Conclusions: Despite the well-characterized acute phase, the long-term sequelae of COVID-19 remain a significant clinical challenge. Identification of late complications is critical for reducing morbidity and understanding the long-term societal and healthcare burden of the pandemic. Multidisciplinary long-term follow-up is warranted, particularly for patients who experienced severe acute illness.},
}
@article {pmid42453233,
year = {2026},
author = {Raina, SK and Kumar, R},
title = {Long TB: Framing post-acute sequelae of tuberculosis as a distinct clinical entity.},
journal = {Journal of family medicine and primary care},
volume = {15},
number = {4},
pages = {1463-1466},
pmid = {42453233},
issn = {2249-4863},
abstract = {Tuberculosis (TB) has historically been declared cured at the point of microbiological clearance. Yet emerging evidence from systematic reviews and cohort studies demonstrates that between 30% and 80% of pulmonary TB survivors experience persistent symptoms, organ damage or functional impairment after treatment completion; a burden that existing outcome metrics fail to capture. We propose the term Long TB, with the formal designation Post-Acute Sequelae of Tuberculosis (PAST-TB), as a conceptual and clinical framework to define, study and address this under-recognised morbidity. Drawing explicit parallels with Long COVID (post-acute sequelae of SARS-CoV-2 or PASC), we argue that the Long TB framing is not merely rhetorical but scientifically grounded, strategically powerful and urgently needed. With approximately 155 million TB survivors alive globally and modelling studies attributing up to 47% of TB-related disability-adjusted life years (DALYs) to the post-treatment period, the case for a systematic post-TB care agenda, anchored by this new terminology is compelling. We attempt to outline the multi-system domains of Long TB, its shared pathological drivers with PASC and the programmatic and research reforms required to move from bacteriological to biological cure as the standard of care.},
}
@article {pmid42454043,
year = {2026},
author = {Wendt, K and Schieck, M and Gille, C and Marschollek, M and Illig, T and Wolff, D and Nee, S},
title = {Biomarkers of post-acute infection syndrome: a systematic literature review.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1741761},
pmid = {42454043},
issn = {1664-3224},
mesh = {Humans ; *Biomarkers/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *SARS-CoV-2 ; *Fatigue Syndrome, Chronic/diagnosis ; },
abstract = {BACKGROUND: Post-acute infection syndrome (PAIS) remained underrecognized before the COVID-19 pandemic, which further increased exposure by introducing a novel global cause. The global burden of post-acute COVID syndrome (PACS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) alone is estimated at several tens of millions affected worldwide. Biomarker discovery is central to improving PAIS diagnosis and may provide therapeutic targets. This review summarizes current knowledge on biomarkers for PAIS, including PACS and ME/CFS.<br><br>METHODS: A systematic literature search was conducted in PubMed and Web of Science. Inclusion criteria were: (1) studies including PAIS patients; (2) reporting laboratory or omics biomarkers; and (3) investigating biomarkers or pathomechanisms of PAIS. Although Guillain-Barr&#xe9; syndrome (GBS) is not PAIS, we have included it as a separate mechanistic comparator due to its prevalence in search results and its clinical and immunological similarities to PAIS.<br><br>RESULTS: A total of 142 studies analyzing PAIS biomarkers were included. GBS was analyzed separately and later compared with the other results. Overall, the reviewed studies employed heterogeneous approaches. While similar types of data were frequently investigated, analytical methods varied and often focused only on a subset of molecules. The results indicate that amino acid, energy, and lipid metabolism, microbiome, mitochondrial stress, and miRNA networks are affected. All pathways are connected via NF-&#x3ba;B.<br><br>DISCUSSION: PAIS is a multisystem disorder rooted in persistent immune activation, metabolic reprogramming, and systemic inflammation, driven not by active viral infection, but by dysregulated host responses. The NF-&#x3ba;B pathway serves as a unifying hub, connecting molecular, cellular, and clinical phenotypes. Our framework enables a shift from symptom-based to mechanism-based classification, paving the way for biologically grounded interventions.<br><br>CONCLUSION: This review synthesizes a broad spectrum of biomarkers in PAIS, integrating findings across pathogens and molecular levels rather than restricting to individual conditions or symptom clusters. This study highlights the differences and commonalities among pathogens and diseases that lead to post-acute sequelae, fills a critical knowledge gap, and provides a foundation for future research and clinical practice. Future studies incorporating multi-omics approaches, longitudinal designs, and larger patient cohorts are needed to validate specific biomarkers and advance the understanding of PAIS.},
}
@article {pmid42454067,
year = {2026},
author = {Brucker, DL and Paul, S},
title = {Long COVID among adults with pre-existing disabilities: Evidence from the 2022 National Health Interview Survey.},
journal = {Journal of disability policy studies},
volume = {2026},
number = {},
pages = {},
pmid = {42454067},
issn = {1044-2073},
abstract = {Long COVID is an emerging public health issue which may be disproportionately impacting adults who had disabilities before the COVID-19 pandemic. We use data from the 2022 National Health Interview Survey to conduct multivariate analyses to compare the odds of having Long COVID among four different disability subpopulations and their working-age reference groups: 1) working-age Medicare beneficiaries, 2) single working-age adults without children who were receiving SSDI and/or SSI, 3) adults who had disabilities before the age of 22; and 4) adults with Veteran's Administration disability ratings. We find that people with disabilities that started before the age of 22 had significantly higher odds of ever having Long COVID (OR: 2.030, p=.007) compared to their reference group, holding all else constant. We did not find significant differences in the odds of ever having Long COVID for the other three sub-populations we identified. These findings point to the importance of ensuring that the systems that support the economic security, education, employment, and healthcare of people with disabilities with an onset before age 22 address this newly emerging concern.},
}
@article {pmid42454777,
year = {2026},
author = {Vernino, S and Bryarly, M and Robbins, NM and Freeman, R and Gibbons, C and Shibao, CA and Biaggioni, I and Kaufmann, H and Levine, BD},
title = {Autonomic Dysfunction in Long COVID Is Distinct From Pure Autonomic Failure.},
journal = {Journal of the American College of Cardiology},
volume = {88},
number = {2},
pages = {245-247},
doi = {10.1016/j.jacc.2026.03.177},
pmid = {42454777},
issn = {1558-3597},
}
@article {pmid42454778,
year = {2026},
author = {Benditt, DG and Keller, C and Mascarhenas, L and Duval, S and Reyes, JL},
title = {Invisible in Full View: Understanding Quantitative Autonomic Study Outcomes in Long-COVID.},
journal = {Journal of the American College of Cardiology},
volume = {88},
number = {2},
pages = {248-250},
doi = {10.1016/j.jacc.2026.05.015},
pmid = {42454778},
issn = {1558-3597},
}
@article {pmid42454903,
year = {2026},
author = {Tang, B and Yang, X and Tian, W and Zhu, J and Liu, W and Di, M and Liu, H and Liang, Z and Chen, Y and Dong, Y},
title = {Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0399625},
doi = {10.1128/spectrum.03996-25},
pmid = {42454903},
issn = {2165-0497},
abstract = {Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.},
}
@article {pmid42435405,
year = {2026},
author = {Costa Monteiro, AC and Qadir, N},
title = {Phenotyping Long COVID: Working Toward Personalized Approaches to Recovery.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1093/annalsats/aaoag194},
pmid = {42435405},
issn = {2325-6621},
}
@article {pmid42436453,
year = {2026},
author = {Rojas, NK and Shafran, R and Stephenson, T and Richards-Belle, A and Ortega-Martin, E and Dalrymple, E and Heyman, I and Newlands, F and McOwat, K and Simmons, R and Pinto Pereira, SM},
title = {Symptom variation up to two years post-SARS-CoV-2 infection in Children and Young People: results from the Children and young people with Long Covid (CLoCk) study.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13951-x},
pmid = {42436453},
issn = {1471-2334},
support = {COV-LT-0022//National Institute for Health and Care Research/ ; 183885//Beryl Alexander Charity/ ; MR/Y009398/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {BACKGROUND: Post Covid-19 Condition (PCC) can fluctuate over time, yet, no in-depth investigation of the heterogeneous PCC trajectories that can exist in children and young people (CYP) has been undertaken. We aim to examine associations between PCC trajectories in CYP over 2-years following infection and (i) factors prior to the COVID-19 pandemic/infection including socio-demographic variables (e.g., age, sex, ethnicity), health and educational needs status and (ii) factors subsequent to infection including the nature, number, functional impact and severity of symptoms, as well as mental health and wellbeing.<br><br>METHODS: 943 PCR-test positive CYP (enrolled January-March 2021) were followed-up over two-years (till January-March 2023). Five PCC trajectory groups were specified: (i) chronic, (ii) recovered, (iii) fluctuating, (iv) late onset and (v) never PCC. These groups were compared in terms of factors at baseline using multinomial logistic regression and concurrent health during the two-year period using Chi-Square/Fisher's Exact tests.<br><br>RESULTS: Baseline factors prior to the pandemic/infection such as female sex, older age, poorer pre-infection mental and physical health, prior healthcare use, and educational needs were strongly and consistently associated with adverse PCC trajectories. Compared to those aged 11-to-14-years at infection, those aged 15-to-17-years had a 2.44 (95%CI:1.39,4.26) higher risk of being in the chronic group (compared to the never group). Similarly, the risk of being in the fluctuating group was 1.57 (95%CI:1.04,2.37), the recovered group was 2.08 (95%CI:1.10,3.92) and the late-onset group was 1.50 (95%CI:1.08,2.07). Other sociodemographic factors, such as ethnicity and region of residence, had more modest and inconsistent associations. PCC trajectories differed by concurrent number, frequency, functional impact and severity of symptoms and mental health. CYP with chronic PCC consistently reported a higher median number of symptoms (5+) compared to the other groups (median symptoms&#x2009;&#x2264;&#x2009;3). Mental health and wellbeing, of the chronic PCC group was also consistently worse (e.g., 41% of the chronic group consistently were classified as 'cases' on the Strengths and Difficulties scale vs 17%-to-2% of the other groups).<br><br>CONCLUSIONS: There were consistent differences between PCC trajectories, in terms of sex, age, pre-infection mental and physical health, healthcare use, and educational needs. Understanding factors associated with PCC trajectory heterogeneity in CYP and how these trajectories differ over time can help with treatment planning.},
}
@article {pmid42437598,
year = {2026},
author = {Egorov, AI and Griffin, SM and Fuzawa, M and Kobylanski, J and Grindstaff, R and Padgett, W and Simmons, SO and Hallinger, DR and Styles, JN and Wickersham, L and Wade, TJ},
title = {Recent SARS-CoV-2 infections and increased antibody responses to viral antigens are associated with greater autoantibody reactivity.},
journal = {Immunology letters},
volume = {},
number = {},
pages = {107212},
doi = {10.1016/j.imlet.2026.107212},
pmid = {42437598},
issn = {1879-0542},
abstract = {BACKGROUND: SARS-CoV-2-induced latent autoimmunity may play a role in long-COVID symptoms. This study explored associations between serum immunoglobulin G (IgG) responses to 18 self-antigens and antibody responses to SARS-CoV-2 and common chronic infections: Epstein-Barr virus (EBV), cytomegalovirus (CMV), Helicobacter pylori, and Toxoplasma gondii.<br><br>METHODS: This cross-sectional study used 179 SARS-CoV-2 convalescent serum samples acquired from biobanks and 123 pre-pandemic serum samples. IgG responses to SARS-CoV-2 spike, receptor binding domain, spike subunit 2, and nucleocapsid antigens were measured using an in-house Luminex multiplexed suspension fluorescence immunoassay. IgG responses to four chronic infections were quantified using commercial ELISA kits. Autoantibody responses to 18 self-antigens were simultaneously measured using a commercially available multiplexed Luminex assay; combined autoantibody reactivity was defined as the geometric mean of the 18 individual autoantibody responses.<br><br>RESULTS: Combined autoantibody reactivity and responses to several individual self-antigens were significantly higher in SARS-CoV-2 convalescent, seropositive individuals than in seronegative pre-pandemic controls. Associations between CMV, EBV, H. pylori, and T. gondii seropositivity and combined autoantibody reactivity were not statistically significant. Stronger antibody responses to antigens of the SARS-CoV-2 spike protein (S, S2, and RBD) in convalescent individuals were significantly associated with greater combined autoantibody reactivity and increased responses to multiple individual self-antigens. Conversely, antibody responses to antigens of CMV, EBV, H. pylori, and T. gondii in corresponding subsets of seropositive individuals were not associated with combined autoantibody reactivity.<br><br>CONCLUSION: SARS-CoV-2 infection and the intensity of IgG responses to the spike protein were associated with increased autoantibody reactivity, a potential indicator of latent autoimmunity.},
}
@article {pmid42444121,
year = {2026},
author = {Case, A and Botdorf, M and Marchesani, N and Leikauf, JE and Letts, R and Maughan, C and Fitzgerald, ML and Higginbotham, M and Swaminathan, AC and Liebovitz, D and Thacker, D and Dandachi, D and Muszynski, JA and Wellnitz, K and Pajor, NM and Jhaveri, R and Gonzalez, SL and Rao, S},
title = {Functional outcomes of children after SARS-CoV-2 infection: An EHR-based cohort study.},
journal = {Journal of pediatric rehabilitation medicine},
volume = {},
number = {},
pages = {18758894261460624},
doi = {10.1177/18758894261460624},
pmid = {42444121},
issn = {1875-8894},
abstract = {BackgroundClinical manifestations of the post-acute sequelae of SARS-CoV-2, or long COVID, have been well-described. However, few pediatric studies explore the impact on everyday function. The objective was to describe functional outcomes for children and youth with long COVID.MethodsA retrospective cohort study of individuals < 21 years of age with COVID-19 infection seeking care at 21 children's hospitals across the United States was conducted. Using a systematic chart review, children with confirmed long COVID were identified by clinician adjudication between March 2020 and December 2022. Outcomes were compared to children with COVID-19 infection without confirmed long COVID. Functional impairments included difficulty participating in school and extracurricular activities, new referrals to rehabilitative therapies, newly modified education plans, and new or worsening mental health symptoms. Descriptive statistics and logistic regression were used to evaluate these outcomes among children with and without long COVID.ResultsAmong 686 children with completed chart review, 651 (95%) had a COVID-19 diagnosis. Functional impairment was documented in 139 (21%) children, of which 59 had clinician-adjudicated long COVID. Compared to infected children without long COVID, children with long COVID had higher odds of school decline (OR 3.5, 95% CI 1.6-7.9, p = 0.002), school support (OR 2.4, 95% CI 1.2-5.0, p = 0.014), and new or worsening behavioral or mental health symptoms (OR 4.6, 95% CI 2.1-9.2, p < 0.001).ConclusionsSignificant functional impairments exist among children and youth following SARS-CoV-2 infection and serve as a reminder to clinicians evaluating children with long COVID to explore everyday function. Future prospective studies with longer follow-up are underway.},
}
@article {pmid42444199,
year = {2026},
author = {Kim, AW and Swana, S and Sokhela, S and Lalla-Edward, S and Manentsa, N and Tsai, AC and Venter, WDF},
title = {Psychiatric symptoms of long COVID among adults: observational case-control study in Johannesburg, South Africa.},
journal = {BJPsych open},
volume = {12},
number = {4},
pages = {e184},
doi = {10.1192/bjo.2026.12049},
pmid = {42444199},
issn = {2056-4724},
abstract = {BACKGROUND: Growing research has underscored the elevated prevalence and burden of psychiatric morbidity among adults living with long COVID. The severity of acute SARS-CoV-2 infection may predict the prevalence and severity of psychiatric symptoms in long COVID. Although Global South countries have faced among the highest incidence rates and burden of COVID-19, little is known about the psychiatric symptoms of long COVID in these regions, especially in Sub-Saharan Africa.<br><br>AIMS: This study aimed to (a) compare the prevalence of long-term psychiatric symptoms between acute COVID-19 infection groups, (b) estimate the associations between COVID-19 severity and long-term psychiatric symptoms, (c) determine the association between long COVID symptoms and psychiatric symptoms, and (d) test the potential mediating effect of long COVID symptoms in the association between acute COVID-19 infection and psychiatric symptoms.<br><br>METHOD: This case-control study took place in Johannesburg, South Africa, between August 2022 and July 2023. A total of 360 adults were categorised into one of four case groups based on initial COVID-19 symptoms: asymptomatic, symptomatic, admitted to hospital and vaccinated controls.<br><br>RESULTS: Prevalence rates of post-traumatic stress disorder (21.1%) and somatic symptoms (22.9%) were elevated. Individuals with symptomatic COVID-19 exhibited the greatest psychiatric morbidity out of all groups, exhibiting the highest levels of depression, suicidality, anxiety, post-traumatic stress disorder, bipolar disorder and somatisation. Acute COVID-19 severity was associated with worse symptoms of depression, somatisation and physical fatigue. Severity of long COVID symptoms was directly associated with psychiatric sequelae.<br><br>CONCLUSIONS: These results call attention to the long-term psychiatric sequelae of SARS-CoV-2 infection and early identification and management of emerging psychiatric symptoms in high-risk COVID-19 survivors.},
}
@article {pmid42445202,
year = {2026},
author = {Cerqueira-Silva, T and Goodwin, B and Araújo, C and Silva, JJ and Pereira, BJ and da Silva, &#xcd;BS and Nunes, S and Marinho, A and Barreto, AP and Barreto, M and Chalhoub, M and Caldas, JR and Rao, V and Coelho, C and Rojas-Hidalgo, A and Maracaja-Coutinho, V and Khouri, R and Cardoso, CR and Barral, A and Barral-Netto, M and Tavares, NM and Dan, J and Boaventura, VS},
title = {CD4[+] T cell signature in long COVID: insights from an unvaccinated cohort.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1823850},
pmid = {42445202},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/virology ; *CD4-Positive T-Lymphocytes/immunology ; *SARS-CoV-2/immunology ; Unvaccinated Persons ; Female ; Male ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Brazil ; Adult ; Cohort Studies ; Immunity, Humoral ; },
abstract = {OBJECTIVE: The pathogenesis of Long COVID (LC) remains poorly understood, with the analysis of immune responses often obscured by variables such as vaccination and reinfection. This study aimed to determine the primary immunological footprint of LC by examining a specific cohort that minimizes these confounding factors.<br><br>METHODS: We analyzed a Brazilian cohort of patients recruited between September 2020 and February 2021, during the first wave of the pandemic (Wuhan-Hu-1 variant), comprising mostly unvaccinated individuals. We assessed humoral responses to SARS-CoV-2 and latent viruses in 104 patients. Additionally, we investigated the immune signatures of CD4[+] T cells in a subset of 6 LC and 4 recovered control (RC) unvaccinated patients, recruited 1 to 2 months after symptom onset, utilizing a combination of flow cytometry and single-cell RNA sequencing.<br><br>RESULTS: Systemic humoral responses to SARS-CoV-2 and reactivated latent viruses were comparable between the LC and RC groups, as were the overall distributions of CD4[+] T cell subsets. However, single-cell RNA sequencing revealed distinct immune signatures. Antigen-responsive CD4[+] T cells in LC patients demonstrated a signature of acute activation, characterized by the upregulation of genes such as CD38 and interferon-stimulated genes, including IFITM1. Furthermore, gene set enrichment analysis indicated that LC patients exhibit increased expression of interferon-alpha/gamma signatures compared to RC. Analysis of the T cell receptor repertoire presented no evidence of clonal expansion.<br><br>DISCUSSION: Our findings imply that LC immunopathology is driven by a qualitative T cell dysfunction characterized by CD4[+] non-proliferative activation more than one month after symptom onset. This pattern is consistent with persistent antigen stimuli, though the underlying mechanism and its therapeutic implications require further investigation.},
}
@article {pmid42446348,
year = {2026},
author = {Kang, AK and Le Huynh, T and Tran, T and Mofina, A},
title = {Role of Occupational Therapy for Persons Experiencing Long COVID: A Rapid Review.},
journal = {Canadian journal of occupational therapy. Revue canadienne d'ergotherapie},
volume = {},
number = {},
pages = {84174261461430},
doi = {10.1177/00084174261461430},
pmid = {42446348},
issn = {1911-9828},
abstract = {BackgroundIndividuals with long COVID experience persisting symptoms that affect daily life, particularly functional performance. Occupational therapists are well positioned to support this population given their expertise across broader health domains.PurposeThis rapid review describes the existing literature on the role of occupational therapy for adults and older adults with long COVID across the healthcare continuum.MethodsA search was conducted across MEDLINE (Ovid), EMBASE, and CINAHL (Ebsco) databases from January 1, 2020, to December 4, 2024.FindingsTwenty-one articles were included for data extraction. The occupational therapy role involved addressing key long COVID symptoms (e.g., fatigue, weakness, and cognitive impairments) that influenced daily occupational performance. Occupational therapy interventions were primarily delivered in rehabilitation settings and included retraining in activities of daily living, cognitive rehabilitation, physical and breathing exercises, patient education, return-to-work planning, and psychosocial support.ConclusionThe occupational therapy role involved addressing long COVID symptoms to regain functional independence to enable occupational engagement, primarily through patient education. Studies focused more on interprofessional, team-based interventions, versus occupational therapy-specific interventions in isolation. This highlights the need for further research on the unique role of occupational therapy within interprofessional teams and along the care continuum for more generalizable findings.},
}
@article {pmid42435145,
year = {2026},
author = {Roche, F and Pichot, V and Bory, C and Bory, N and Hupin, D},
title = {Transcutaneous vagus nerve stimulation for long COVID-associated autonomic dysfunction: mechanistic rationale and emerging clinical evidence.},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {},
number = {},
pages = {},
pmid = {42435145},
issn = {1619-1560},
}
@article {pmid42426705,
year = {2026},
author = {Biering, K and Schiøttz-Christensen, B and Willert, MV and Nielsen, KJ and Kolstad, HA and Kyndi, M and Vestergaard, JM},
title = {The impact of SARS-CoV-2 infection on work participation, sickness absence and general practitioner consultations in the Danish population - a register-based matched cohort study.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-28486-8},
pmid = {42426705},
issn = {1471-2458},
abstract = {OBJECTIVES: Many persons infected with SARS-CoV-2 experienced prolonged symptoms after the acute phase of the infection (long-COVID). We aimed to investigate whether SARS-CoV-2 infection increased the risk of long-term sickness absence, low work participation, and high use of general practitioners in persons in the Danish workforce.<br><br>METHODS: In a register-based cohort study, we identified 261,325 persons from the workforce who tested positive for SARS-CoV-2 in Denmark. These were matched with persons who tested negative by time, sex, age, and industry and analysed with conditional logistic regression. The outcomes were long-term sickness absence, low work participation and high number of contacts to general practitioners, all measured during year 1 after test. We adjusted for work participation or contacts to general practitioners, both measured during year 1 before test, respectively, and for vaccination status, comorbidity, and educational level. We stratified the result by sex, age, and industry to identify any effect modification by these factors.<br><br>RESULTS: Most persons infected with SARS-CoV-2 were not on long-term sickness absence (98.3%). However, compared to persons tested negative, SARS-CoV-2 infected had an increased risk of long-term sickness absence (Odds Ratio (OR):2.92[2.82;3.03]) and low work participation (OR:1.32[1.30;1.34]). The risk was higher among women and middle-aged and older persons. Furthermore, the risk was highest in public administration, education and health services, culture and arts, and lowest in agriculture, forestry and fishing. We found an increased risk of high number of contacts to general practitioners among SARS-CoV-2 infected (OR:1.61[1.60;1.63]), however more uniformly distributed across subgroups.<br><br>CONCLUSION: Infection with SARS-CoV-2 was associated with a higher risk of long-term sickness absence, low work participation and high number of contacts to general practitioners during year 1 after test. The associations differed across sex, age and industry, especially in relation to sickness absence.},
}
@article {pmid42428381,
year = {2026},
author = {Muthian, S and Hadjichristofis, M},
title = {Shoulder Injuries Secondary to Proning: Sequelae of Long COVID Syndrome: A Case Report.},
journal = {Journal of orthopaedic case reports},
volume = {16},
number = {7},
pages = {116-120},
pmid = {42428381},
issn = {2250-0685},
abstract = {INTRODUCTION: Prolonged proning is widely used in the management of severe acute respiratory distress syndrome (ARDS), most notably during the COVID-19 pandemic. Although brachial plexus injuries are recognized complications, structural shoulder injuries remain rarely reported.<br><br>CASE REPORT: We report a case of a patient who developed a glenoid fracture and persistent shoulder dysfunction following prolonged proning for COVID-19-related ARDS. Clinical assessment, radiological findings, and management strategies are detailed.<br><br>DISCUSSION: This case highlights unique mechanical and physiological risk factors for structural shoulder injury during proning, including obesity, diabetic neuropathy, prolonged intensive care unit stay, and positioningrelated stress.<br><br>CONCLUSION: Structural glenohumeral injuries should be considered in patients presenting persistent shoulder dysfunction after prolonged proning. Awareness and preventive positioning strategies are essential.},
}
@article {pmid42428921,
year = {2026},
author = {Kassymbek, S and Abduldayeva, A and Safonov, N},
title = {Global prevalence of post-COVID-19 condition (Long COVID): a systematic review and meta-analysis of observational studies.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1839646},
pmid = {42428921},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Post-Acute COVID-19 Syndrome ; Observational Studies as Topic ; *Global Health/statistics &amp; numerical data ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID is an umbrella term for persistent, relapsing, or newly developed health problems after SARS-CoV-2 infection, whereas post-COVID-19 condition (PCC) refers more specifically to the World Health Organization clinical case definition. Reported prevalence varies substantially because of differences in terminology, operational definitions, study populations, follow-up duration, hospitalization status, and symptom ascertainment. This systematic review and meta-analysis synthesized global observational evidence on Long COVID/PCC prevalence and examined major sources of variability.<br><br>METHODS: A systematic review and meta-analysis was conducted according to PRISMA 2020 principles. PubMed/MEDLINE, Scopus, Web of Science, and the WHO COVID-19 Global Literature Database were searched for studies published from 1 January 2020 to 23 February 2026. Observational studies were eligible if they included individuals with confirmed or probable SARS-CoV-2 infection, reported Long COVID/PCC or persistent post-COVID symptoms at least 4 weeks after acute infection, and provided numerator and denominator data. Terminology and operational case definitions were extracted separately. Prevalence estimates were pooled using a random-effects model with logit transformation and back-transformation. Heterogeneity was assessed using Cochran's Q, I[2], tau[2], and prediction intervals. Subgroup and sensitivity analyses were performed.<br><br>RESULTS: Twenty-two studies contributing 27 prevalence estimates and more than 200,000 participants were included. The primary estimate-level pooled prevalence was 30.8% (95% CI 26.8-35.0). Heterogeneity was extreme: Q = 8031.9, df = 26, p < 0.001; I[2] = 99.7%; tau[2] = 0.252 on the logit scale. The prediction interval was 14.0-54.8%. Pooled prevalence was higher among hospitalized cohorts (37.9%, 95% CI 29.5-47.1) than among non-hospitalized, community-based, or mixed cohorts (26.2%, 95% CI 22.0-30.9). WHO-defined PCC yielded lower prevalence (22.8%, 95% CI 14.3-34.4) than broader symptom-based definitions (39.7%, 95% CI 30.5-49.5). Cohort-level sensitivity analysis yielded a similar prevalence of 31.0% (95% CI 26.8-35.4).<br><br>CONCLUSION: Long COVID/PCC represents a substantial post-acute public health burden. However, because heterogeneity was extreme, the pooled prevalence should be interpreted as a descriptive summary of heterogeneous observational evidence rather than as a single precise global rate. Standardized definitions, harmonized surveillance, transparent reporting, rehabilitation pathways, and multidisciplinary care models are needed.},
}
@article {pmid42431744,
year = {2026},
author = {Guedj, E and Beckman, D},
title = {Dopaminergic vulnerability in long COVID: striatal PET imaging at the brain-body interface.},
journal = {EBioMedicine},
volume = {},
number = {},
pages = {106369},
doi = {10.1016/j.ebiom.2026.106369},
pmid = {42431744},
issn = {2352-3964},
}
@article {pmid42431745,
year = {2026},
author = {Liu, YK and Persaud, D and Vieira, EL and Braga, J and Rusjan, P and Miler, L and Rabin, JS and McCluskey, T and Boileau, I and Chao, T and Bagby, M and Narciso, L and Gray, LR and Vasdev, N and Desmond, K and Kloiber, S and Warsh, J and Husain, MI and Smart, K and Wang, W and Meyer, JH},
title = {Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms.},
journal = {EBioMedicine},
volume = {},
number = {},
pages = {106339},
doi = {10.1016/j.ebiom.2026.106339},
pmid = {42431745},
issn = {2352-3964},
abstract = {BACKGROUND: Dopaminergic neurons are vulnerable to injury from gliosis and have high density of ACE2 receptors, but the integrity of dopaminergic neurons has not been investigated in long COVID. This study examined whether vesicular monoamine transporter 2 (VMAT2) binding, index of dopamine-releasing neuron density, is reduced in the striatum in long COVID and associated with neuropsychiatric symptoms.<br><br>METHODS: This case-control study (Aug 2022-Apr 2025, Toronto, Canada) included 24 adults with long COVID and 24 age-matched healthy controls, and the healthy control sample was extended to 43 for exploratory analyses. Primary outcome was comparison of (+)[[11]C]DTBZ binding potential (BPND), PET measure of VMAT2 binding, between long COVID and control groups across ventral striatum, dorsal putamen, and dorsal caudate. Secondary outcomes were associations of regional (+)[[11]C]DTBZ BPND with neuropsychiatric measures (apathy, anhedonia, motor retardation) in long COVID.<br><br>FINDINGS: (+)[[11]C]DTBZ BPND was significantly lower in 24 individuals with long COVID vs 24 age-matched healthy controls (linear mixed effects model, P = 4 &#xd7; 10[-5]; vs 43 controls, P = 6 &#xd7; 10[-4]). Apathy, motor slowing (secondary outcomes) and memory decline (exploratory outcome) correlated with lower (+)[[11]C]DTBZ BPND in ventral striatum, dorsal putamen and caudate, respectively (|r| = 0.48-0.58, P = 0.0029-0.018).<br><br>INTERPRETATION: Findings of reduced VMAT2 binding may reflect reduced dopaminergic terminal integrity in long COVID. Loss of dopamine nerve terminals may be contributing to symptom correlates of apathy, motor slowing and memory decline suggesting improved function of dopaminergic synapses as a new therapeutic direction to treat long COVID.<br><br>FUNDING: Canadian Institutes of Health Research (191851).},
}
@article {pmid42432030,
year = {2026},
author = {Horberg, MA and Jefferson, C and Watson, E and Kim, S and Deneal, AN and Gebo, KA and Hogan, BC and Humes, E and Althoff, KN},
title = {Effects of HIV status and vaccination on long COVID conditions within an integrated health care system.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01761-w},
pmid = {42432030},
issn = {2730-664X},
support = {U01AI069918//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; },
abstract = {BACKGROUND: COVID infection has been linked to long-term effects known as Long COVID Conditions (PCC), presenting within 30-120 days post-acute COVID infection. Few studies have focused on PCC incidence among people with HIV (PLWH). Additionally, the effect of vaccination, especially among PLWH, is unclear on the risk for PCC. We evaluate PCC incidence among PLWH compared with people without HIV (PWoH), as well as the effect of COVID vaccination, within an integrated closed healthcare system with high ascertainment of COVID-19 testing.<br><br>METHODS: Adult patients with a positive polymerase chain reaction test for COVID between 1/1/2020-1/31/2022 were matched PLWH to PWoH by month of test, age, race, sex, vaccination status, using 1:3 variable ratio matching. PCC was defined as presenting with at least one of 17 previously identified conditions incident in the 30-120 days post first positive test date. We determined the effect of COVID vaccination on subsequent development of PCC using an unmatched PLWH/PWoH population analyzed by multivariate regression modeling.<br><br>RESULTS: We show that 749 PLWH matched to 2,236 PWoH for PCC incidence evaluation and 492 (PLWH) and 71,844 PWoH for vaccination analysis. PLWH have 25% higher risk of PCC than PWoH. Gastrointestinal and other nervous system disorders are significantly higher among PLWH. Vaccination has significant impact on acute-persistent PCC risk but not late incident PCC without impact by HIV status.<br><br>CONCLUSION: PLWH have higher risk of PCC. Vaccination lowers persistent symptom risk, but not late incident PCC risk. Vaccination and vigilance for PCC is encouraged.},
}
@article {pmid42432680,
year = {2026},
author = {Sasso, EM and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S},
title = {Neurological impairment in long COVID: implications for neurodegenerative disease.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08607-y},
pmid = {42432680},
issn = {1479-5876},
support = {489798//Stafford Fox Medical Research Foundation/ ; 1199502//National Health and Medical Research Council/ ; 47107//Mason Foundation/ ; 49979//McCusker Charitable Foundation/ ; 4676//Ian and Talei Stewart, the Buxton Foundation/ ; 4579//Blake Beckett Trust Foundation/ ; 4570//Alison Hunter Memorial Foundation/ ; 4575//Change for ME Charity/ ; Dr John Hamwood//Dr John Hamwood/ ; 4879//Henty Community/ ; },
abstract = {BACKGROUND: It has been six years since the COVID-19 pandemic and, despite substantial advances in management, the disease sequelae known as long COVID continues to represent a significant medical and societal burden. Long COVID is characterised by persistent neurological and neurocognitive symptoms, including brain fog, memory deficits, attention impairments, and fatigue, lasting for months after acute SARS-CoV-2 infection.<br><br>MAIN BODY: In this review, we collated emerging neurological findings related to long COVID, discussing neurodegenerative processes associated with long COVID, potential clinical implications and research limitations. Neurological and neurocognitive manifestations arise through multiple mechanisms, including direct SARS-CoV-2 invasion of the central nervous system and peripheral lymphocyte infiltration. Additionally, neurovascular damage potentially contributes to neurodegeneration through neuronal injury, impaired neurogenesis, microvascular abnormality and sustained neuroinflammation.<br><br>CONCLUSION: Understanding the mechanisms underlying neurological and neurocognitive symptoms is essential for developing long-term monitoring strategies and targeted interventions to mitigate neurocognitive decline in individuals with long COVID.},
}
@article {pmid42433775,
year = {2026},
author = {Abera, EG and Himbaro, SA and Megersa, SW and Ashine, AH and Tukeni, KN and Gebremichael, EH},
title = {Emerging trends in post-COVID immune dysregulation: a narrative review.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {7},
pages = {4362-4370},
pmid = {42433775},
issn = {2049-0801},
abstract = {BACKGROUND: Long coronavirus disease (COVID), or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a multi-system condition associated with persistent immune dysregulation, autoimmunity, and vascular perturbations. Understanding these immunological mechanisms is essential for guiding clinical management and therapeutic strategies.<br><br>METHODS: We conducted a narrative review of peer-reviewed human studies published between January 2020 and August 2025, using PubMed/Medline, Scopus, and Web of Science, supplemented by manual searches. Studies reporting immunological assessments in long COVID patients, recovered individuals, or healthy controls were included. Findings were extracted and synthesized thematically across six domains: humoral and cellular immunity, autoimmune signatures, proteomic/metabolic and vascular dysregulation, viral persistence, complement/coagulation/thromboinflammation, and pediatric long COVID.<br><br>RESULTS: Long COVID is characterized by persistent low-grade inflammation, T- and B-cell dysregulation, and prolonged adaptive immune activation. Humoral responses remain elevated, while T-cell exhaustion and loss of coordination between immune compartments are common. Autoimmune phenomena, including latent and polyautoimmunity targeting cytokines, thyroid antigens, and interferons, are frequently observed. Proteomic, metabolic, and vascular perturbations, complement activation, and thromboinflammatory processes contribute to ongoing symptoms. Viral persistence and early immune biomarkers predict long COVID development. These immune alterations correlate with fatigue, cognitive impairment, respiratory dysfunction, and reduced quality of life in both adults and children.<br><br>CONCLUSION: SARS-CoV-2 infection leaves a lasting immunological footprint marked by chronic inflammation, adaptive immune dysregulation, autoimmunity, and vascular perturbations. Integrating longitudinal immune assessments, biomarker profiling, and early predictive markers is critical for identifying high-risk individuals and informing interventions to reduce long COVID morbidity.},
}
@article {pmid42434549,
year = {2026},
author = {Ruiz-Casas, C and Tarrés-Freixas, F and Roca, N and Pérez, M and Contreras, E and Martín, L and Bernaus, O and Olvera, A and Ruiz-Riol, M and Brander, C and Usai, C and Vergara-Alert, J and Segalés, J},
title = {Persistent neurological and behavioral alterations after SARS-CoV-2 infection in an optimized K18-hACE2 mouse model.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1871084},
pmid = {42434549},
issn = {1664-302X},
abstract = {INTRODUCTION: Persistent neurological symptoms are among the most prevalent and debilitating manifestations of post-COVID-19 Condition (PCC), affecting millions of individuals worldwide. PCC is a chronic multisystemic syndrome that develops in over 30% of adults following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its major clinical and socioeconomic impact, the biological mechanisms underlying PCC remain poorly understood, underscoring the need for robust and translational animal models.<br><br>METHODS: We conducted a longitudinal study in K18-hACE2 mice, integrating virological, immunological, histopathological, and behavioral assessments from acute infection through 60 days post-inoculation.<br><br>RESULTS: SARS-CoV-2-inoculated mice developed persistent neurobehavioral impairments despite the absence of detectable viral replication in the brain. These alterations were associated with sustained immune dysregulation in both pulmonary and neural tissues, persistent pulmonary pathology, and a reduction in vagus nerve cross-sectional area. Notably, several long-term outcomes exhibited marked sex-dependent differences that mirrored clinical observations in human PCC.<br><br>DISCUSSION: Our findings demonstrate that K18-hACE2 mice recapitulate key neurological and immunopathological features of PCC and may constitute a valuable experimental model for investigating the mechanisms underlying PCC-associated neurological sequelae. This model may also facilitate the development and preclinical evaluation of targeted therapeutic interventions.},
}
@article {pmid42434926,
year = {2026},
author = {Yehoshua, A and Black, RM and Di Fusco, M and Carter, B and Sienko, D and Lopez, S and McColgan, MD and Rudolph, AE and Yang, J},
title = {Evaluation of long-term healthcare utilization and costs associated with COVID-19 among adults and children in the US.},
journal = {Journal of medical economics},
volume = {29},
number = {1},
pages = {1942-1954},
doi = {10.1080/13696998.2026.2699643},
pmid = {42434926},
issn = {1941-837X},
mesh = {Humans ; *COVID-19/economics/epidemiology ; Retrospective Studies ; United States ; Female ; Child ; Male ; Adult ; Middle Aged ; Adolescent ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Insurance Claim Review ; Child, Preschool ; *Health Expenditures/statistics &amp; numerical data ; Aged ; Young Adult ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {AIMS: This study assessed long-term healthcare resource utilization (HCRU) and direct medical costs associated with COVID-19 among adults and children in the United States. Using a large national claims database, we quantified the incremental healthcare burden during the year following a first COVID-19 diagnosis compared to matched controls without a COVID-19 diagnosis.<br><br>MATERIALS AND METHODS: This retrospective cohort study used data from the IQVIA PharMetrics Plus database. Patients with a COVID-19 diagnosis (U07.1) between June 1 and November 30, 2022, were matched 1:1 to non-COVID-19 controls based on age, sex, region, insurance type, Charlson Comorbidity Index, and baseline HCRU. Outcomes were HCRU and all-cause healthcare costs accrued during the post-acute period (&#x2265;31&#x2009;days after first COVID-19 diagnosis), measured cumulatively through 1, 3, 6, 9, and 11&#x2009;months of follow-up. Generalized linear models estimated cost ratios.<br><br>RESULTS: The study included 944,627 patients with a COVID-19 diagnosis (U07.1) and an equal number of matched controls. Compared with matched controls, mean total costs during 11&#x2009;months of post-acute follow-up were 27% higher among adults ($11,508 vs $9,040; p&#x2009;<&#x2009;0.001) and 42% higher among pediatric patients with COVID-19 ($3,997 vs $2,812; p&#x2009;<&#x2009;0.001). Costs were higher for COVID-19 cases at all follow-up time points. Among adults at the 11-month follow-up time, costs increased with acute infection severity, with mean costs of $10,372 for outpatients, $36,848 for hospitalized patients, and $51,643 for ICU patients, compared with $8,617, $16,926, and $17,620, respectively, among matched controls (all p&#x2009;<&#x2009;0.001). Among adults, cost ratios peaked at 1&#x2009;month of follow-up (1.32; 95% CI: 1.31-1.33) and declined to 1.15 (95% CI: 1.14-1.15) at 11&#x2009;months.<br><br>CONCLUSIONS: There were significantly higher post-acute HCRU and costs among both adults and pediatrics with a COVID-19 diagnosis compared to matched controls without one, with elevated cost differences persisting up to 12&#x2009;months post-infection.},
}
@article {pmid42424907,
year = {2026},
author = {Kamseng, P and Chantaramanee, N and Sompan, R and Rareongjai, S},
title = {Integrative hematological and transcriptomic analysis reveals monocyte alterations and molecular signatures of inflammatory-coagulation crosstalk in long COVID.},
journal = {Computational biology and chemistry},
volume = {124},
number = {Pt 2},
pages = {109226},
doi = {10.1016/j.compbiolchem.2026.109226},
pmid = {42424907},
issn = {1476-928X},
abstract = {Long COVID has complicated immunological and coagulation dysregulations. The study explores the pathophysiological pathways by integrating clinical hematological characteristics with transcriptome bioinformatics. In a comparison of 45 patients (21 with Long COVID and 24 asymptomatic controls), the Long COVID cohort demonstrated significantly reduced total WBC counts (p = 0.031) and circulating monocytes (p = 0.008), as well as reduced platelet counts (p = 0.040) and prolonged APTT (p = 0.016). To better understand these findings, transcriptome analysis of the public dataset GSE251849 was performed applying DESeq2, Gene Set Enrichment Analysis (GSEA), and a Protein-Protein Interaction (PPI) network assessed through the Maximal Clique Centrality (MCC) algorithm. Transcriptomic profiling demonstrated significant enrichment of inflammation, cellular stress, and coagulation pathways. The MCC analysis identified IL6, MYC, CDKN1A, SERPINE1, CD44, and PLAUR as the key hub genes. The significant decrease in circulating monocytes, along with upregulation of CD44, indicates monocyte depletion due to enhanced endothelium adherence. Furthermore, the significant upregulation of SERPINE1 and PLAUR underscores the important connection between chronic vascular inflammation and severe fibrinolysis resistance (hypofibrinolysis). These findings establish a strong biological basis for the clinical features of Long COVID, highlighting an immunothrombosis proposed mechanistic model driven by cellular stress and hypofibrinolysis, thus pinpointing prospective targets for future diagnostics and therapeutics.},
}
@article {pmid42425362,
year = {2026},
author = {Acanfora, D and Nolano, M and Acanfora, C and Colella, C and Provitera, V and Caporaso, G and Rengo, G and Incalzi, RA and Casucci, G},
title = {Vagal cholinergic denervation of the gastric mucosa in Long-COVID-19: in vivo evidence of structural autonomic dysfunction.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108973},
doi = {10.1016/j.ijid.2026.108973},
pmid = {42425362},
issn = {1878-3511},
abstract = {OBJECTIVES: Dysautonomia has been increasingly recognized as a key feature of Long-COVID-19, potentially contributing to persistent gastrointestinal and systemic symptoms. Reduced vagal activity observed in these patients may reflect structural damage to autonomic fibers. We hypothesized that dysautonomic manifestations in Long-COVID-19 are associated with impaired cholinergic innervation of the gastric mucosa.<br><br>METHODS: We conducted a case-control study including 12 patients with Long-COVID-19 and 8 control subjects undergoing routine gastroscopy. Gastric mucosal biopsies were analyzed using immunohistochemistry with the pan-neuronal marker protein gene product 9.5 (PGP 9.5) and vasoactive intestinal peptide (VIP) as a marker of cholinergic fibers. Nerve fiber density was quantified in both fundus and antrum samples.<br><br>RESULTS: Compared with controls, Long-COVID-19 patients exhibited a significant reduction in mucosal innervation density: 2.1 vs 3.9 nm/&#xb5;m&#xb3; (p<0.01) in the fundus and 1.9 vs 3.9 nm/&#xb5;m&#xb3; (p<0.05) in the antrum. The reduction in cholinergic innervation was more pronounced in the fundus (p<0.01) andalso evident in the antrum (p=0.01). Gastric nerve density correlated with HRV parameters (LF/HF ratio: R=0.50, p<0.05) and NT-proBNP levels (R=0.52, p<0.01).<br><br>CONCLUSIONS: Patients with Long-COVID-19 exhibit reduced gastric mucosal cholinergic innervation. This structural autonomic impairment may represent an anatomical substrate underlying dysautonomia in Long-COVID-19.},
}
@article {pmid42426196,
year = {2026},
author = {Wood, H},
title = {Autoantibodies could trigger neurological symptoms of long COVID.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42426196},
issn = {1759-4766},
}
@article {pmid42426643,
year = {2026},
author = {González-Andrade, F},
title = {Strict long COVID, symptom persistence, and functional decline among community-dwelling older adults in Quito, Ecuador: a cross-sectional study.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07976-9},
pmid = {42426643},
issn = {1471-2318},
abstract = {BACKGROUND: Long COVID is an increasingly recognized health concern in older adults, yet data from Latin America remain limited. Older adults may be particularly vulnerable to post-COVID sequelae because of frailty, multimorbidity, and reduced physiological reserve. This study aimed to estimate the prevalence of strict long COVID among older Ecuadorian adults and to characterize persistent post-COVID symptoms, clinical correlates, and functional/cognitive worsening.<br><br>METHODS: We conducted a cross-sectional study of 1,050 community-dwelling adults aged 65 years or older with PCR-confirmed SARS-CoV-2 infection in Quito, Ecuador. Data were collected through structured face-to-face interviews and cognitive screening. Strict long COVID was defined as symptoms persisting for more than 12 weeks after SARS-CoV-2 infection. Symptoms lasting 4-12 weeks were classified as persistent post-COVID symptoms but were not considered strict long COVID. Multivariable logistic regression was used to evaluate factors associated with strict long COVID.<br><br>RESULTS: The mean age was 74.2&#x2009;&#xb1;&#x2009;7.5 years, and 565 participants (53.8%) were women. Overall, 191 participants met criteria for strict long COVID, corresponding to a prevalence of 18.2% (95% CI, 16.0-20.6). Persistent post-COVID symptoms lasting 4-6 weeks and 7-12 weeks were reported by 401 (38.2%) and 458 (43.6%) participants, respectively. Participants with strict long COVID had higher frequencies of dyspnea, cognitive impairment, sleep disturbance, myalgia, depression, anxiety, and difficulty sleeping. Functional/cognitive worsening was more frequent among participants with strict long COVID than among those without strict long COVID (53.4% vs. 36.6%; p&#x2009;<&#x2009;0.001), particularly for walking or climbing stairs. In multivariable analysis, severe or critical acute COVID-19 was independently associated with strict long COVID (adjusted OR, 2.36; 95% CI, 1.62-3.41; p&#x2009;<&#x2009;0.001). Female sex, age&#x2009;&#x2265;&#x2009;81 years, incomplete vaccination, diabetes with organ involvement, hospitalization, and care dependence were not independently associated with strict long COVID.<br><br>CONCLUSION: Strict long COVID affected nearly one in five older adults with PCR-confirmed SARS-CoV-2 infection in Quito, Ecuador. Severe or critical acute COVID-19 was the main factor independently associated with strict long COVID, and affected participants had greater functional/cognitive worsening. These findings support integrating post-COVID screening, functional assessment, and geriatric rehabilitation into primary care for older adults in Latin America.},
}
@article {pmid42419335,
year = {2026},
author = {, },
title = {Efficacy and safety of rivaroxaban, colchicine, and famotidine-loratadine with specialist supportive clinical care for fatigue in patients with post-COVID-19 condition in the UK: a multisite, open-label, randomised controlled trial.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(26)00242-2},
pmid = {42419335},
issn = {1474-4457},
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 or post-COVID-19 condition (also known as long COVID) affects 1-5% of adults globally, most commonly with fatigue, and no evidence-based therapies are available. We aimed to evaluate the efficacy of repurposed medications in fatigue management in adults with long COVID.<br><br>METHODS: We did a phase 3, four-group, randomised, controlled, adaptive platform, open-label drug trial nested within a pragmatic, multicentre, cluster-randomised trial of an integrated care pathway (ICP) for long COVID across 12 UK National Health Service (NHS) specialist long COVID care clinics in the UK. Participants had to be adults (>18 years) with long COVID who had not been hospitalised with COVID-19. In addition to NHS specialist-led long COVID care (hereafter, usual care), participants in the ICP trial could receive multiorgan MRI and clinical decision support and/or app-based rehabilitation. Initially, participants in the ICP trial were invited to enrol in the drug trial, but slow recruitment to the drug trial led to establishment of additional drug-only trial sites. Participants enrolled at either ICP trial sites or drug-only trial sites were randomly assigned (1:1:1:1) to receive colchicine 500 &#x3bc;g twice daily, rivaroxaban 10 mg once daily, famotidine 40 mg with loratadine 10 mg once daily, or no drug for 12 weeks. All participants received usual care. Randomisation was done electronically in blocks (various block sizes) and stratified by site, birth sex, ICP trial group allocation, and being a new or previous patient of a drug-only site. The primary endpoint was 12-week fatigue, assessed with the Fatigue Assessment Scale (FAS; with scores ranging from 10 [no fatigue] to 50 [debilitating fatigue], and a >10% change considered clinically meaningful) among randomly assigned individuals who had available baseline and 12-week data, adjusting for baseline fatigue and clinically relevant covariates. Secondary endpoints included 24-week FAS. The nested drug trial is registered, ISRCTN10665760. The trial is complete.<br><br>FINDINGS: Of 6035 eligible participants, 778 (383 co-enrolled in the ICP trial and 395 directly enrolled in the drug trial) were randomly assigned between Aug 22, 2022, and Aug 7, 2024 to colchicine (n=192), famotidine-loratadine (n=193), rivaroxaban (n=197), or no drug (usual long COVID care only; n=196). The mean age of participants was 46 years (SD 12&#xb7;4), 495 (64%) of 778 were female, and 91 (12%) were from a non-White ethnic group. Across all trial groups, there was severe baseline fatigue (mean FAS score 36&#xb7;8 [SD 7&#xb7;49]) and a clinically relevant mean FAS reduction of 4&#xb7;3 points to 32&#xb7;5 (SD 9&#xb7;13) at 12 weeks. Adjusted analyses showed small, statistically significant FAS reductions in the colchicine (-1&#xb7;49 points [95% CI -2&#xb7;92 to -0&#xb7;06], p=0&#xb7;041) and famotidine-loratadine (-1&#xb7;48 points [-2&#xb7;88 to -0&#xb7;08], p=0&#xb7;038) groups, but not in the rivaroxaban group (-1&#xb7;06 points [-2&#xb7;47 to 0&#xb7;35, p=0&#xb7;139), compared with no study drug at 12 weeks. However, 24-week FAS scores, 12 weeks after drug cessation, were not significantly different between groups. Treatment was well tolerated, with ten serious adverse events (requiring hospitalisation but unrelated to trial drugs) reported in eight (1&#xb7;0%) of the 778 participants, five of which were in three participants in the rivaroxaban group.<br><br>INTERPRETATION: In participants with long COVID, severe fatigue reduced in all study groups-including the no drug group-over 12 weeks, with small additional reductions in the colchicine and famotidine-loratadine groups compared with the no drug group. Modest effects on FAS were not sustained after drug withdrawal. Long-term long COVID symptom benefit is unlikely with these drugs alone. Future trials could investigate the use of these or other repurposed drugs in specific subgroups of patients with long COVID, combination therapies, and how care is delivered.<br><br>FUNDING: UK National Institute for Health and Care Research.},
}
@article {pmid42419817,
year = {2026},
author = {Tamariz, L and Palacio, A},
title = {Author Response to "Dysautonomia in Long COVID: Why Sex Differences Matter in Cardiovascular Risk Assessment".},
journal = {Clinical medicine &amp; research},
volume = {24},
number = {2},
pages = {50-51},
doi = {10.3121/cmr.2026.2146},
pmid = {42419817},
issn = {1554-6179},
}
@article {pmid42419818,
year = {2026},
author = {Mattioli, AV},
title = {Dysautonomia in Long COVID: Why Sex Differences Matter in Cardiovascular Risk Assessment.},
journal = {Clinical medicine &amp; research},
volume = {24},
number = {2},
pages = {49-50},
doi = {10.3121/cmr.2026.2127},
pmid = {42419818},
issn = {1554-6179},
}
@article {pmid42421498,
year = {2026},
author = {Carnevali, F and Muollo, MC and Biagini, L and Rossi, G},
title = {Xenosialylation as immunological chimerism: a host-centered unifying model for viral and post-vaccination immune complications.},
journal = {European cytokine network},
volume = {37},
number = {2},
pages = {55-77},
pmid = {42421498},
issn = {1952-4005},
mesh = {Humans ; Glycosylation ; *COVID-19/immunology/prevention &amp; control ; *SARS-CoV-2/immunology ; *Vaccination/adverse effects ; *COVID-19 Vaccines/immunology/adverse effects ; Neuraminic Acids/immunology ; *Models, Immunological ; Animals ; },
abstract = {Severe immune-mediated complications following viral infections and vaccinations, including COVID-19 and anti-SARS-CoV-2 immunization, display remarkable clinical overlap despite occurring in distinct biological contexts. In a previous hypothesis-driven work, we proposed that metabolic incorporation of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into human glycoconjugates-defined as xenosialylation-may contribute to post-infectious and post-vaccination immune dysregulation. We further suggest that this phenomenon may represent a form of "immunological chimerism", in which host glycoconjugates incorporate non-self molecular structures that predispose the immune system to varying degrees of immune imbalance. In its most severe manifestation, this process may culminate in a profound state of immune dysregulation characterized by loss of immune tolerance, aberrant antibody responses, cytokine storm, and thrombo-inflammatory pathology, which we define as "immunological marasmus". In the present paper, we extend this conceptual framework by integrating glycobiology, Fc immunoglobulin glycosylation, endothelial biology, and sex-dependent immune regulation into a unified, testable immunopathogenic model. We hypothesize that interindividual differences in the extent, tissue distribution, and persistence of xenosialylation may influence susceptibility to exaggerated innate and adaptive immune responses following antigenic challenge. In this context, immune activation may unmask pre-existing xeno-sialylated self-structures embedded within host glycans, promoting varying degrees of glycan dysregulation, autoantibody production, immunothrombosis and chronic inflammatory sequelae. We further propose circulating anti-Neu5Gc antibodies as functional biomarkers for risk stratification and outline preventive strategies based on dietary modulation of xenosialic acid exposure. Taken together, this expanded model provides a potential mechanistic framework for understanding the shared immunological features of post-viral syndromes and vaccine-related adverse immune reactions, while offering a basis for experimental validation and future approaches to personalized risk mitigation.},
}
@article {pmid42421939,
year = {2026},
author = {Li, E and Shi, M and Huang, S},
title = {New-onset allergic diseases after SARS-CoV-2 infection: mechanistic hypotheses and emerging strategies for risk stratification.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1879430},
pmid = {42421939},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; *Hypersensitivity/immunology/epidemiology ; Animals ; Risk Assessment ; },
abstract = {Multinational cohort studies consistently associate SARS-CoV-2 infection with elevated incidence of allergic diseases, with hazard ratios of 2.25 for asthma and 1.23 for allergic rhinitis persisting beyond six months post-infection; whether this excess risk reflects de novo allergic sensitization or preferential unmasking of pre-existing subclinical atopy remains to be established. Yet mechanisms bridging acute viral illness to delayed allergic phenotypes remain incompletely understood. This review synthesizes recent advances across epithelial biology, immunology, and neuroimmune interactions to propose a unified mechanistic framework organized around three interconnected axes. First, epithelial injury during COVID-19 triggers passive IL-33 release while inducing active TSLP and IL-25 production. These alarmins act through mechanistically distinct pathways to converge on type 2 immune priming, which is established and reinforced by epigenetic memory in group 2 innate lymphoid cells and dendritic cells. Second, regulatory T cell depletion and, hypothetically, hematopoietic stem and progenitor cell epigenetic reprogramming driven by acute interleukin-6 elevation may generate immune cell progeny with persistently altered inflammatory responsiveness, while dendritic cells adopt Th2-polarizing phenotypes that lower the threshold for allergic sensitization; the direct contribution of hematopoietic reprogramming to Th2-skewed allergic outcomes remains to be demonstrated. Third, mast cells undergo direct spike protein-mediated activation via angiotensin-converting enzyme 2 receptors, and alarmin-primed mast cells establish bidirectional crosstalk with sensory neurons that amplifies neuroinflammation and links long COVID symptoms to heightened allergic susceptibility. Together, these axes define a post-infectious vulnerability window during which allergen encounters trigger exaggerated type 2 responses. Risk stratification incorporating disease severity, circulating biomarkers including immunoglobulin E and eosinophil counts, and genetic susceptibility variants may identify individuals requiring targeted surveillance, while mechanistically informed interventions such as low-dose interleukin-2, mast cell stabilizers, and alarmin-targeted biologics warrant prospective evaluation in convalescent cohorts.},
}
@article {pmid42421948,
year = {2026},
author = {Liu, A and Chen, H and Liu, Q and Al-Azab, M and Shaher, F and Li, J and Liu, T and Yang, M},
title = {Cardiovascular sequelae of Long COVID: immune dysregulation inflammation as central drivers.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1815269},
pmid = {42421948},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications ; Post-Acute COVID-19 Syndrome ; *Cardiovascular Diseases/immunology/etiology ; *Inflammation/immunology ; Immunity, Innate ; *SARS-CoV-2/immunology ; Animals ; Adaptive Immunity ; },
abstract = {Long coronavirus disease 2019 (Long COVID-19), also referred to as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has emerged as a major global health challenge. Common manifestations include fatigue, dyspnea, cognitive dysfunction, and exercise intolerance. Beyond these systemic manifestations, the enduring cardiovascular manifestations are increasingly identified as core characteristics of Long COVID-19 syndromes secondary to SARS-CoV-2 infection, encompassing myocarditis, ischemic and non-ischemic heart disease, arrhythmias, heart failure, and thrombotic events. Accumulating evidence suggests that immune dysregulation and persistent inflammation are central drivers of cardiovascular injury in Long COVID. Persistent activation of innate and adaptive immune pathways fosters endothelial injury, thrombo-inflammation, and adverse myocardial remodeling. In this review, we focus on current clinical and experimental evidence to delineate the immune-mediated mechanisms underlying cardiovascular sequelae in Long COVID and explore potential therapeutic strategies targeting persistent inflammation and immune dysregulation.},
}
@article {pmid42421959,
year = {2026},
author = {Bansal, A},
title = {Proteomic landscapes of post-COVID condition: biomarkers and translational pathways.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1783192},
pmid = {42421959},
issn = {1664-3224},
mesh = {Humans ; *Biomarkers/blood/metabolism ; *Proteomics/methods ; *COVID-19/complications/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; },
abstract = {Post-COVID condition is a heterogeneous, multi-system sequela of SARS-CoV-2 infection that imposes substantial socioeconomic burden and currently needs validated diagnostic biomarkers or established therapeutic pathways. This brief communication synthesises blood-based proteomic and targeted biomarker evidence and organises it into three overlapping pathophysiological domains: persistent immune dysregulation (IL-6, IL-20, MCP-1 and TNF- α), endothelial dysfunction and disordered haemostasis (VEGF-A, P-selectin, vWF, ICAM-1 and D-dimer); and neurological injury (NFL, GFAP, NAAA, LXN, NBL1, HAGH). Across studies, no single protein provides adequate diagnostic performance; phenotype-linked multi-analyte panels show the greatest promise. Researching post-COVID conditions requires harmonised case definitions, cross-platform validation, and the integration of coagulation assays and extracellular vesicle profiling to improve tissue signal detection.},
}
@article {pmid42422160,
year = {2026},
author = {Duncan, JP and Jackson, M and Cooper, CJ and Anzinger, JJ and Ehikhametalor, K and Facey, KA and Cloherty, G and Tulloch-Reid, MK},
title = {Persistent Neurological Symptoms in Chronic Disease Patients After COVID-19 Infection in Jamaica: A Retrospective Cohort Study Exploring Clinical Manifestations of Long COVID in a Low and Middle Income Country.},
journal = {Health science reports},
volume = {9},
number = {7},
pages = {e72761},
pmid = {42422160},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: There is uncertainty about the long term effects of COVID-19 infection. We describe the dominant reported symptoms and their sociodemographic risk factors in a sample of Jamaican patients with non-communicable diseases (NCD) and laboratory determined infection status.<br><br>METHODS: A retrospective cohort study (February 20, 2023-September 12, 2023) of patients from the University Hospital of the West Indies (UHWI) were identified through participation in the Caribbean COVID-19 Metabolic Health Study (CCMHS) or ICU admissions between March 2020 and March 2021 with a positive PCR. COVID-19 infection status was based on anti-nucleocapsid (anti-N) antibodies in those without PCR reports. Participants were classified as "Exposed" if they had positive anti-N antibodies or a positive PCR test and "Unexposed" if they had negative anti-N antibodies. Bivariate analyses compared current symptoms and quality of life of exposed and unexposed participants. Logistic regression explored factors associated with memory loss.<br><br>RESULTS: Eighty-six persons (62 exposed and 24 unexposed; mean age 54.1&#x2009;&#xb1;&#x2009;13.4 years; median "time since first COVID-19 diagnosis" 1.9 years) participated in the study. "Not [feeling] quite right" (59.3%), joint pains (46.5%), fatigue (45.4%), numbness/tingling (43.0%), headache (26.7%), and shortness of breath (23.3%) were the most common symptoms that were similarly reported in persons regardless of infection status. Memory loss was more common among exposed participants (41.9% vs. 12.5%, p&#x2009;=&#x2009;0.01) and among those with COVID-19 infection, self-reported depression/anxiety increased the odds of this symptom (OR 6.7 (1.7-25.7).<br><br>CONCLUSION: Cardiopulmonary and musculoskeletal symptoms were common among NCD patients regardless of previous COVID-19 infection. However, memory loss was more common up to 2 years after initial COVID-19 infection. Prospective cohorts of long COVID in subpopulations are critical to elucidating its natural history.},
}
@article {pmid42422161,
year = {2026},
author = {Santis, B and Baldo, F and Vento, G and Nobile, S},
title = {Impact of COVID-19 on Subsequent Lung Function in Childhood: A Systematized Review.},
journal = {Health science reports},
volume = {9},
number = {7},
pages = {e72793},
pmid = {42422161},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: The SARS-CoV-2 infection can lead to transiently altered lung function in adults, but data is less clear in children. We aimed to summarize the available evidence about respiratory outcomes after COVID-19 in childhood.<br><br>METHODS: We conducted a literature search on post-COVID-19 lung function tests (LFT) on the Medline and Cochrane databases, including studies published between 2019 and 2025.<br><br>RESULTS: Three hundred forty-seven publications were identified, and 20 were selected. Results are presented in two sections, based on the duration of follow-up. Most studies included spirometry, whereas many of them presented data from diffusing lung capacity for carbon monoxide, multiple breath nitrogen washout, fractional exhaled nitric oxide, impulse oscillometry, 6-minute walking test, and interrupter resistance. Five papers described no association between COVID-19 and respiratory outcomes, nor a link between the persistence of symptoms and the outcomes. Other authors reported a mild obstructive pattern which showed reversibility post bronchodilators, or a restrictive pattern, particularly when long-COVID was evident. Some papers showed that pulmonary function may be influenced by the initial severity of the SARS-CoV-2 infection.<br><br>CONCLUSION: Some studies reported no clear association between lung function impairment and previous history of COVID-19. Other authors reported mild, transient consequences. A small number of papers concluded that severe infection, which is relatively rare in children, might affect pulmonary function. The main limitation of this review was the high heterogeneity of the included studies, especially regarding the COVID-19 severity, the age groups, the LFT details, and the duration of follow-up.},
}
@article {pmid42422442,
year = {2026},
author = {Rodríguez-Pérez, MP and Huertas-Hoyas, E and León-Herrera, S and Gómez-Bravo, R and García-Bravo, C and Rodríguez-Rodríguez, E and Poveda-García, A},
title = {Beyond functional independence: symptom burden and emotional difficulties in pediatric long COVID-a cross-sectional exploratory study.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1878494},
pmid = {42422442},
issn = {2296-2360},
abstract = {BACKGROUND: Pediatric Long COVID poses significant challenges to daily functioning, yet its real-world impact remains poorly understood. Standard functional independence measures may not fully capture the condition's consequences in developmentally relevant contexts.<br><br>METHODS: A cross-sectional exploratory study was conducted with 27 children and adolescents (mean age 15.48&#x2009;&#xb1;&#x2009;2.31 years; 70.4% female) meeting WHO criteria for Long COVID. Functional independence was assessed using the WeeFIM and emotional functioning with the SDQ. Contextual functioning variables-school attendance, grade repetition, and withdrawal from recreational activities-were collected as exploratory indicators of real-world impact.<br><br>RESULTS: Despite high symptom burden-fatigue (81.5%), difficulty concentrating (63.0%), and malaise (55.6%) among the most prevalent, with 88.9% experiencing symptoms for over 24 months-WeeFIM scores were near-ceiling across all domains (total: 114.56&#x2009;&#xb1;&#x2009;20.71/126). Contextual data revealed substantial real-world impact: only 18.5% attended school regularly, 11.1% had repeated an academic year, and 85.2% had withdrawn from previously enjoyed activities. SDQ total scores fell within the normal range (12.07&#x2009;&#xb1;&#x2009;5.04), though emotional symptoms were slightly elevated (5.59&#x2009;&#xb1;&#x2009;2.34). A significant negative correlation was found between SDQ total score and WeeFIM cognition (rho&#x2009;=&#x2009;-0.570, p&#x2009;=&#x2009;0.0019), and a coherent brain fog-mood-concentration symptom cluster was identified. These results are preliminary, hypothesis-generating findings from a convenience sample and should be interpreted with caution regarding generalizability.<br><br>CONCLUSIONS: Children and adolescents with Long COVID may maintain basic functional independence while experiencing significant symptom burden, emotional difficulties, and substantial restrictions in school, recreational, and social domains. These findings highlight the limited sensitivity of standard functional measures and underscore the need for more comprehensive, context-sensitive assessment approaches in pediatric Long COVID practice.},
}
@article {pmid42422532,
year = {2026},
author = {Bao, W and Ye, G and Wang, T and Quan, X and Zhu, Q and Fan, L and Li, H and Zeng, W and Mu, J and Zhu, R and Liu, J and Zhang, Y and Niu, X},
title = {Dynamic multivariate patterns of brain structure-neuropsychiatric symptom associations in long COVID.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag232},
pmid = {42422532},
issn = {2632-1297},
abstract = {Long COVID presents with heterogeneous and persistent neuropsychiatric symptoms, suggesting possible shared neural underpinnings. However, the dynamic brain structure-symptom relationships and their potential for predicting long-term outcomes remain unclear. We conducted a longitudinal study of 144 individuals with long COVID (mean age: 37.8 ± 10.1 years, 48.6% male). All participants experienced mild COVID-19 and were not hospitalized. Structural MRI and comprehensive psychiatric and cognitive assessments were performed at 1, 2 and 12 months post-infection. A cohort of 68 healthy controls (mean age: 36.0 ± 10.3 years; 41.2% male) completed the same assessment protocol at baseline. Regularized canonical correlation analysis was employed to identify multivariate associations between 13 psychiatric and cognitive measures and both grey matter volume and cortical thickness, and to assess whether early structural features predicted symptom outcomes at 1 year. Neuropsychiatric symptoms were linked to coordinated structural covariance patterns across distributed brain regions in long COVID; these associations strengthened from 1 to 3 months post-infection and were absent in controls. A stable cognitive-affective symptom dimension showed the strongest brain-behaviour coupling. Notably, the neural substrates of this coupling diverged over time: grey matter volume associations remained localized to prefrontal-limbic circuits, whereas cortical thickness associations expanded to frontoparietal regions. Critically, reduced grey matter volume in the right cuneus and superior frontal gyri, along with decreased cortical thickness in the left supramarginal gyrus at 3 months post-infection, were significantly linked to poorer executive function and greater fatigue 1 year later. Our findings delineate evolving neuroanatomical signature of long COVID, where distinct patterns of grey matter volume and cortical thickness underpin a core symptom profile and predict long-term neuropsychiatric symptoms. These results provide insight into the neural mechanisms of long COVID and identify specific targets for monitoring and early intervention.},
}
@article {pmid42422850,
year = {2026},
author = {Vera-López, &#xc1; and Tilves-Santiago, D and Ramírez-Sánchez, JM and Docío-Fernández, L and García-Mateo, C and Bustillo-Casado, M and García-Caballero, A},
title = {Improving respiratory disease detection through SSL-enhanced acoustic analysis and exercise-rest measurements.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1864436},
pmid = {42422850},
issn = {2296-858X},
abstract = {BACKGROUND: Voice analysis has emerged as a promising non-invasive approach for monitoring respiratory and systemic health conditions. However, subtle physiological alterations are often difficult to capture using recordings collected at rest. In addition, combining traditional acoustic descriptors with modern self-supervised speech representations may provide complementary information for clinical voice analysis.<br><br>OBJECTIVES: This study evaluates a generalized screening model integrating stress-induced acoustic analysis with machine learning. We investigate how physical exertion and the fusion of traditional acoustic features with self-supervised learning embeddings (such as wav2vec 2.0 and WavLM) enhance the diagnostic sensitivity of vocal and respiratory signals. Post-Acute Sequelae of SARS-CoV-2 (PASC) is used as a case study to evaluate the proposed framework.<br><br>METHODS: Utilizing the DICOPERIA-Voice dataset (n = 154), we collected recordings of sustained vowel phonation (/a/) and voluntary coughing at two clinical moments: resting state and following a physiological stress protocol (six-minute walk and one-minute sit-to-stand tests). We employed a dual-feature extraction strategy, combining traditional acoustic biomarkers with high-dimensional Self-Supervised Learning (SSL) embeddings from wav2vec 2.0, WavLM and HuBERT. Binary classification (PASC vs. Healthy) was performed using Logistic Regression, evaluated via stratified 5-fold cross-validation.<br><br>RESULTS: Physical exertion significantly improved classification performance and reduced model variability across all tasks. The fusion of acoustic features, WavLM and wav2vec 2.0 achieved peak F1-scores of 82.2% for vowel phonation and 80.8% for coughing both in post-exercise conditions. A cross-task late fusion model aggregation reached the highest overall performance, with an F1-score of 87.7%.<br><br>CONCLUSION: Incorporating Self-Supervised Learning representations into acoustic analysis improves the sensitivity of voice-based screening, while post-exercise measurements further enhance the robustness and consistency of classification. Together, these strategies provide a scalable and objective framework for detecting respiratory and vocal sequelae in chronic or post-viral conditions. With further validation, this approach could be integrated into routine functional assessments, offering a rapid, non-invasive adjunct to clinical decision-making.},
}
@article {pmid42424864,
year = {2026},
author = {Yang, S and Xuan, L},
title = {Comment on "the neuropsychiatric features of long COVID in older adults and the potential association with neuroinflammation: Preliminary observations in a small cohort".},
journal = {Journal of the neurological sciences},
volume = {489},
number = {},
pages = {126076},
doi = {10.1016/j.jns.2026.126076},
pmid = {42424864},
issn = {1878-5883},
}
@article {pmid42411649,
year = {2026},
author = {Theeler, J and Comellas, AP and Gehl, C and Garvin, L and Garg, A and Fain, SB and Hoth, KF},
title = {Clinical neuropsychological evaluation of patients referred from a post-COVID subspeciality clinic.},
journal = {The Clinical neuropsychologist},
volume = {40},
number = {5},
pages = {1339-1358},
doi = {10.1080/13854046.2025.2536700},
pmid = {42411649},
issn = {1744-4144},
mesh = {Humans ; Female ; *Neuropsychological Tests ; Middle Aged ; Male ; Adult ; *COVID-19/complications/psychology ; *Depression/diagnosis/etiology ; *Anxiety/diagnosis ; *Fatigue/diagnosis/etiology/psychology ; Processing Speed ; Post-Acute COVID-19 Syndrome ; *Cognitive Dysfunction/diagnosis/etiology ; Executive Function/physiology ; },
abstract = {Objective: To describe neuropsychological assessment findings of patients referred from a post-COVID subspecialty clinic. Methods: Clinical data were examined for 54 patients referred between March 2021 and May 2023. Assessment included objective cognitive performance, performance validity testing, self-report of cognitive symptoms (BRIEF-A), depressive and anxiety symptoms (BDI-II/BAI), and fatigue (PROMIS Fatigue-4a). Objective cognitive measures were grouped into domains and examined through (1) one sample t-tests comparing each domain score to the normative mean characterized using Cohen's d, and (2) the frequency of impaired performance and elevated symptoms (±1.5 SD). Clinically elevated symptoms of depression, anxiety, and fatigue were examined. Results: Exclusion criteria resulted in a final sample of 46 (mean age= 48.5; 72% female). The mean cognitive domain scores of the sample all fell within 1 SD of expectations based on normative data. Examination of effect sizes using Cohen's d suggested that verbal comprehension and perceptual reasoning were significantly above the mean (small effect) while executive function, language, and processing speed were reduced (small effect). The Metacognition index of the BRIEF-A was elevated driven by Working Memory (80.5%). Elevated symptoms of depression (59.1%)/anxiety (75.0%) were frequent and not associated with objective cognitive scores. Elevated fatigue (56.5%) was associated with impaired processing speed performance. Conclusions: Individuals with long COVID reported significant difficulty with working memory capacity. Participants demonstrated a pattern of reduced performance in domains of executive function, language, and processing speed, although group means were within 1 SD of normative expectations. Clinically elevated fatigue was associated with reduced processing speed performance.},
}
@article {pmid42413051,
year = {2026},
author = {Butzin-Dozier, Z and Ji, Y and Deshpande, S and Anzalone, AJ and Wang, LC and Hurwitz, E and Kumar, M and Patel, RC and Sun, J and Robertson, M and Mertens, A and Camacho-Rivera, M and Colford, JM and Hubbard, AE and Madlock-Brown, C},
title = {Black Patients Underdiagnosed With Long COVID In The US Compared With White Patients.},
journal = {Health affairs (Project Hope)},
volume = {45},
number = {7},
pages = {775-781},
doi = {10.1377/hlthaff.2025.00179},
pmid = {42413051},
issn = {2694-233X},
mesh = {Humans ; *White People/statistics &amp; numerical data ; United States/epidemiology ; *COVID-19/diagnosis/ethnology ; *Black or African American/statistics &amp; numerical data ; Female ; Post-Acute COVID-19 Syndrome ; Male ; Middle Aged ; SARS-CoV-2 ; Aged ; Adult ; White ; Electronic Health Records ; },
abstract = {Long COVID has debilitating effects but is inconsistently diagnosed because of subjective criteria, limited treatments, and variations in health care access. We analyzed electronic health records from the National Clinical Cohort Collaborative for patients diagnosed with acute COVID-19 in the US between January 2022 and March 2023. Using six race and ethnicity categories, we evaluated 222 symptoms and long COVID diagnoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, code U09.9) within twelve months after infection. We assessed the relationship between race and ethnicity and long COVID diagnosis, adjusting for patient covariates and long COVID symptomatology set to the presence of at least one documented long COVID-associated symptom. Among 2.4 million patients, Black patients were less likely to be diagnosed with long COVID than White patients under a scenario in which a symptom was present and health care monitoring was at least bimonthly. For the remaining racial and ethnic groups, we found no statistically significant differences in long COVID diagnoses compared with White patients. Although the magnitude was small, the difference in diagnosis likelihood suggests the presence of potential diagnostic bias.},
}
@article {pmid42414929,
year = {2026},
author = {Milic, J and Pelizzoni, A and Gozzi, L and Albano, T and Ricciardetto, M and Menozzi, M and Cuomo, G and Mancini, G and Mussini, C and Guaraldi, G},
title = {Reshaping long COVID care through patient-reported needs.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13773-x},
pmid = {42414929},
issn = {1471-2334},
abstract = {BACKGROUND: Long COVID is a multisystem condition characterized by persistent or fluctuating symptoms following acute SARS-CoV-2 infection. Despite increasing scientific evidence, the alignment between patient needs and healthcare delivery remains limited. This study aimed to assess unmet clinical, psychological, and lifestyle needs among individuals previously evaluated at the Modena Long COVID Clinic and to inform a patient-centered redesign of Long COVID services.<br><br>METHODS: This observational study included individuals assessed at least once at the Modena Long COVID Clinic (Italy) between August 2020 and July 2025. Participants with valid email and phone contacts were invited to complete an online questionnaire exploring unmet needs across clinical, mental health, welfare, and lifestyle domains. The questionnaire also assessed Long COVID symptom clusters and health-related quality of life (HR-QoL) using the EQ-5D-5&#xa0;L and EQ-VAS. Data were compared between the first clinical visit (baseline) and the follow-up survey.<br><br>RESULTS: Of 707 individuals contacted, 162 (22.9%) completed the survey (median age 56 years; 54.9% male). At follow-up, 80.1% reported at least one Long COVID symptom cluster, with significant increases in musculoskeletal (30.1% vs. 60.8%), neurocognitive (23.5% vs. 52.4%), and psychological (25.3% vs. 51.2%) domains. EQ-5D-5&#xa0;L scores remained stable (median 83.0 vs. 84.1; p&#x2009;=&#x2009;0.927), while self-rated health improved (60 vs70; p&#x2009;<&#x2009;0.001). Unmet needs were common: 22.2% reported insufficient access to specialist consultations, 15.4% lacked psychological support, and 15.5% reported unmet needs for pain management.<br><br>CONCLUSIONS: This study identifies substantial gaps between patient needs and existing care structures, emphasizing the need for a dynamic, cluster-based, and patient-centered approach. The results support the redesign of Long COVID services into five operational pillars: functional triage, empowerment and education, integrated cluster clinics, continuity of care through case management, and outcome-based evaluation. Such reorganization may enhance perceived health and well-being even when overall disability remains stable.<br><br>TRIAL REGISTRATION: Clinical trial number not applicable.},
}
@article {pmid42414935,
year = {2026},
author = {Vickers, JK and Levitan, EB and Howell, CR and Montgomery, AP and Jones, R and Lund, FE and Erdmann, N},
title = {Differences in diagnostic coding in long COVID: sociodemographic and symptom interference factors.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13943-x},
pmid = {42414935},
issn = {1471-2334},
support = {T32HD071866/NH/NIH HHS/United States ; 3U19AI142737-04S1/NH/NIH HHS/United States ; },
abstract = {PURPOSE: We aimed to test associations of participant-reported Long COVID symptom interference with life activities with Long COVID symptoms, presence of U09.9 Long COVID diagnosis code, demographics, and clinical factors. In a subgroup, we documented coding related to Long COVID and post-exertional malaise in the electronic medical record (EMR).<br><br>METHODS: Using a cross-sectional analysis (n&#x2009;=&#x2009;205) of participant data from a Long COVID survey, we tested associations with Chi-square, Fisher's exact, or Fisher-Freeman-Halton exact statistical tests and Independent Samples T-tests.<br><br>RESULTS: Participants were predominately female (67%) with a mean age of 50.9 years. Participants were White (50.0%), African American (47.5%), and Asian (2.5%); 1.5% reported Hispanic ethnicity. 41% of participants reported high Long COVID symptom interference with life activities. Participants who were older (p=.028), were female (p=.002), were obese (p=.049), had worse general health (p<.001), worse physical health (p<.001), had worse mental health (p<.001), and had U09.9 diagnosis (p<.001) were more likely to experience high symptom interference. Among participants with high symptom interference, there were no significant associations with U09.9 diagnosis code. EMR sub-analysis (n&#x2009;=&#x2009;100) revealed that among participants that reported high symptom interference (n&#x2009;=&#x2009;39), 64% (n&#x2009;=&#x2009;25) had a code related to Long COVID.<br><br>CONCLUSION: Although we found discrepancies between self-reported measures and EMR coding, we did not find evidence of demographic biases in diagnosis among participants with high symptom interference.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid42415070,
year = {2026},
author = {Wunderle, M and Ribeiro, A and Lethen, I and Schmaderer, C and Wallraven, T},
title = {Persistent impairments in muscle function and symptom burden in post-COVID syndrome: a prospective longitudinal study.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08579-z},
pmid = {42415070},
issn = {1479-5876},
abstract = {BACKGROUND: Post-COVID syndrome (PCS) is characterized by persistent heterogeneous symptoms after SARS-CoV-2 infection, yet objective biomarkers for symptom severity and longitudinal disease trajectories remain limited. We aimed to characterize muscle function over time in PCS and examine its relationship with symptom burden and neuroaxonal injury markers.<br><br>METHODS: In this prospective observational study, patients fulfilling WHO criteria for PCS underwent standardized assessments at baseline (BL) and six-month follow-up (FU). Muscle function was assessed using a multidimensional handgrip strength (HGS) protocol capturing mean force (Fmean), fatigability (fatigue ratio), and recovery capacity alongside clinical symptom measures. Analyses included longitudinal assessment within the PCS cohort, comparisons with COVID-19 recovered controls, analysis of symptom persistence, and matched cohort analyses including HGS measures and circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).<br><br>RESULTS: Among 204 participants (102 PCS, 102 recovered controls) PCS patients showed lower Fmean and higher fatigability at BL and FU (both p&#x2009;<&#x2009;0.01). Muscle function parameters remained largely stable over six months, with only modest improvement in recovery (p&#x2009;=&#x2009;0.015). HGS parameters correlated with symptom burden (&#x3c1; &#x2248; -0.28 to -0.33), and BL impairments were associated with worse fatigue and depressive symptoms at FU (e.g., Fmean-PHQ-9: &#x3b2; = -0.11, p&#x2009;=&#x2009;0.022; fatigue ratio-FSS: &#x3b2;&#x2009;=&#x2009;1.66, p&#x2009;=&#x2009;0.008). Exploratory analyses suggested slightly higher NfL and GFAP levels in PCS in some models, without consistent associations with muscle function or symptoms.<br><br>CONCLUSIONS: HGS is persistently reduced in PCS over at least six months and aligns with symptom burden. Multidimensional HGS assessment may provide a practical objective marker of functional impairment and symptom persistence in PCS. Neuroaxonal injury markers showed modest elevations in PCS in some analyses but appeared unrelated to muscle performance, suggesting partially distinct mechanisms.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT05635552. Registered 1 December 2022 - Retrospectively registered, https://clinicaltrials.gov/study/NCT05635552?term=NCT05635552&amp;rank=1&amp;tab=study.},
}
@article {pmid42415099,
year = {2026},
author = {Wang, K and Lee, CCL and Qu, G and Tang, CTK and Yiu, HHE and Yang, X and Wong, CKM and Wong, SY and Yip, BHK},
title = {Individual preferences for the design of a health coaching-based lifestyle promotion program among middle-aged adults in Hong Kong: a discrete choice experiment.},
journal = {Health and quality of life outcomes},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12955-026-02584-y},
pmid = {42415099},
issn = {1477-7525},
abstract = {OBJECTIVES: Health coaching is an effective approach to motivating lifestyle modifications and preventing the onset of non-communicable diseases. This study aims to examine middle-aged adults' preferences for health coaching programs to improve public acceptance of these programs.<br><br>METHODS: A discrete choice experiment (DCE) was conducted among adults aged 35-59 years in Hong Kong who were recruited from a population-based cohort established to evaluate outcomes related to long COVID. The DCE attributes and levels were selected based on a literature review and qualitative interviews (n&#x2009;=&#x2009;10) with users and providers from a local health coaching program. The selected attributes included program duration, delivery mode of coaching sessions, frequency of coaching sessions, availability of blood tests, core program format, smartwatch usage, and out-of-pocket payment. An online survey with 10 choice sets was conducted to collect participants' choices regarding health coaching services with (copayment scenario, 10 choices) and without out-of-pocket payment (no copayment scenario, 10 choices). A mixed logit model and a latent class model were used for the analysis.<br><br>RESULTS: A total of 912 responses were collected, of which 554 valid records were included in the analysis. In the copayment scenario, participants preferred programs that provided a smartwatch and a lower copayment rate. In the no copayment scenario, participants preferred a moderate coaching frequency, communication via phone calls or text messages, and provision of a smartwatch. Distinct preference groups were identified, including those who preferred face-to-face versus remote modes of delivery, high versus low contact frequency, and those who were sensitive versus insensitive to cost.<br><br>CONCLUSIONS: Lower copayment and smartwatch provision improve acceptance of health coaching programs. Substantial preference heterogeneity for program duration, health coaching frequency, and delivery mode was found. While material incentives are important for improving acceptance of health coaching, considerable preference heterogeneity for non-monetary attributes suggests that options for health coaching program intensity can be offered along with subsidies or lower out-of-pocket payment to promote these services.},
}
@article {pmid42415124,
year = {2026},
author = {Sewell, PE and Jensen, C},
title = {Clinical rationale for thymic restoration in adult immunosenescence.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12979-026-00584-6},
pmid = {42415124},
issn = {1742-4933},
abstract = {Age-related thymic involution is a central feature of immunosenescence and intersects with multiple "hallmarks of aging", including genomic instability, telomere attrition, mitochondrial dysfunction, and chronic inflammation. The decline in thymic epithelial integrity and FOXN1-driven thymopoiesis reduces naïve T-cell output, contracts TCR repertoire diversity, and perturbs central tolerance, contributing to increased susceptibility to infection, cancer, and autoimmunity. These changes occur alongside broader immune-aging phenomena such as inflammaging and frailty and are reflected in poorer vaccine responses and altered outcomes to novel pathogens such as SARS-CoV‑2. This review integrates mechanistic, preclinical, and human data to reassess the adult thymus as a therapeutic target. Higher-confidence domains for thymic restoration include cancer immunosurveillance, infectious disease vulnerability, vaccine responsiveness, and post-treatment immune reconstitution, supported by modeling of age-related disease incidence, transplant and HIV cohorts, and new observational links between radiographic thymic health, mortality, and immunotherapy outcomes. High-plausibility but less directly validated domains include autoimmunity, chronic herpesvirus control, HIV immunological non-responders, and post-acute infection syndromes such as long COVID, which share convergent patterns of T-cell dysfunction and persistent immune activation. The translational landscape spans hormonal and somatotropic modulation (sex steroid ablation, growth hormone/ghrelin), cytokine and growth-factor strategies (IL‑7, IL‑22, KGF/BMP4, FGF21), cell- and tissue-engineering approaches leveraging thymic epithelial stem cells and FOXN1-reprogrammed stromal cells, and gene-therapy concepts such as intrathymic AAV delivery of FOXN1, AIRE, chemokines, and stromal-support pathways. Collectively, these data support the biological plausibility of adult thymus restoration but highlight that robust, domain-specific clinical benefits have not yet been demonstrated in controlled trials. Future work should prioritize harmonized structural and functional biomarkers, domain-focused interventional studies in high-risk populations, and combined strategies that situate thymus-directed interventions within broader efforts to modify immune and organismal aging.},
}
@article {pmid42415194,
year = {2026},
author = {Lehoux, MC and Houle, M and Saey, D and Tétreau, C and Lefebvre, A and Mathieu, E and Drapeau, C},
title = {Evaluating the feasibility and preliminary effects of a group-based telerehabilitation program in individuals with persistent dyspnea after COVID-19 (TEPCO): a pilot randomized controlled study.},
journal = {Pilot and feasibility studies},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40814-026-01876-w},
pmid = {42415194},
issn = {2055-5784},
abstract = {BACKGROUND: Many COVID-19 survivors have been shown to experience at least one persistent symptom or deficit following infection, impacting their functioning and quality of life. However, knowledge about the appropriate care and rehabilitation needs of individuals with Long COVID remains fragmented. More research is needed to understand the impact of rehabilitation or telerehabilitation programs on Long COVID symptoms, quality of life, and work ability. This is a pilot randomized controlled trial to evaluate the feasibility of the study procedures and to compare the preliminary effects of a rehabilitation program delivered remotely (experimental group) or in-person (control group) for an adult (≥ 18 years) with confirmed COVID-19 and persistent dyspnea at least eight weeks post-infection.<br><br>METHODS: Participants were randomly assigned to either the telerehabilitation or in-person group using a computer-generated allocation sequence. An 8-week rehabilitation program, including cardiovascular, muscular, balance training, and respiratory exercises, was provided to both groups. Outcomes assessed included feasibility (recruitment rate, dropout rate, adherence rate, occurrence of adverse events, and patient satisfaction). Secondary outcomes comprised preliminary effect measures including exercise capacity, functional capacity, functional independence in daily life, quality of life, and clinical frailty.<br><br>RESULTS: Twenty-one participants aged between 29 and 75 (median age 52) were recruited to the study. Thirty-nine (39) eligible individuals were approached, and 22 participants consented to participate in the study (56.4% consent rate). One participant withdrew before the start of the program due to scheduling issues, resulting in 21 participants included in the analysis. Eight participants in the in-person group and ten participants in the telerehabilitation group attended at least 75% of the sessions. No adverse events related to the intervention were reported during the study period. Participants' satisfaction levels were high, with 90% strongly agreeing to the quality of services received in the telerehabilitation group. For the exercise capacity (pedaling time), there was a Group*Time interaction (F(1, 16)&#x2009;=&#x2009;6.1, &#x3b7;p[2]&#x2009;=&#x2009;.28) and a main effect of time (F(1, 16)&#x2009;=&#x2009;20.9, &#x3b7;p[2]&#x2009;=&#x2009;.57). A main effect of time was also detected for the One-Minute Sit-to-Stand Test (F(1, 16)&#x2009;=&#x2009;8.1, &#x3b7;p[2]&#x2009;=&#x2009;.34) in both groups.<br><br>CONCLUSIONS: This pilot randomized controlled study demonstrated the feasibility and safety of delivering a supervised group-based rehabilitation intervention remotely compared with in-person delivery to individuals with Long COVID characterized by persistent dyspnea eight weeks post-infection. These findings apply to a relatively young, non-hospitalized population and may not be generalizable to all Long COVID phenotypes. The protocol proved feasible in our clinic, showing favorable recruitment, dropout, and adherence rates, as well as a low occurrence of adverse events and high satisfaction. Preliminary observations on clinical outcomes suggest potential benefits of telerehabilitation compared to in-person delivery; these findings are exploratory and intended to inform future research rather than provide definitive conclusions. Further studies, including larger multicenter RCTs across Qu&#xe9;bec regions, are needed to evaluate the effects, safety and generalizability of supervised group-based telerehabilitation interventions for individuals with Long COVID.<br><br>TRIAL REGISTRATION: ClinicalTrial.gov,&#xa0;NCT06952127. Registered on 28 April 2025-retrospectively registered. https://clinicaltrials.gov/study/NCT06952127.},
}
@article {pmid42415750,
year = {2026},
author = {Onavbavba, G and Badaru, A and Durojaye, AB and Adigwe, OP},
title = {Knowledge, awareness, and perception of healthcare professionals towards Long COVID in Nigeria.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1768068},
pmid = {42415750},
issn = {2296-2565},
mesh = {Humans ; Nigeria/epidemiology ; Female ; Male ; *COVID-19 ; Cross-Sectional Studies ; *Health Knowledge, Attitudes, Practice ; Adult ; Post-Acute COVID-19 Syndrome ; *Health Personnel/psychology/statistics &amp; numerical data ; Surveys and Questionnaires ; SARS-CoV-2 ; Middle Aged ; Young Adult ; },
abstract = {INTRODUCTION: Long COVID is a complex condition with prolonged symptoms that develop after COVID-19 infection and continue beyond 12 weeks. This study aimed to assess healthcare professionals' knowledge, awareness, and perceptions of Long COVID in Nigeria.<br><br>METHODS: A cross-sectional study using multistage random sampling was conducted amongst licensed healthcare professionals in Nigeria, including physicians, pharmacists, nurses, and medical laboratory scientists. A validated questionnaire was administered to practitioners in selected health facilities. Data from 405 respondents were analysed using the Statistical Package for the Social Sciences (SPSS) version 25.<br><br>RESULTS: A total of 405 valid responses were obtained, reflecting a response rate of 81%. Male and female participants were of similar proportions, as indicated by 50.1 and 49.9%, respectively. Over a quarter (26.3%) of the sample were not aware of Long COVID, and of the respondents who had heard about the condition, more than half (58.5%) indicated that they obtained their information from the internet. Participants' understanding of Long COVID was assessed to be limited, with a mean knowledge score of 6.38&#x202f;&#xb1;&#x202f;2.86. As indicated by more than half (50.5%) of the study cohort, there is a lack of prioritisation in the management of post-COVID symptoms in Nigeria, as well as inadequate frameworks to mitigate the effects of the condition (45.1%). Male participants had significantly higher knowledge scores than females, with p&#x202f;=&#x202f;0.006 and a standardised beta coefficient of 0.158, indicating a small-to-moderate effect size.<br><br>CONCLUSION: The study identified knowledge gaps amongst healthcare professionals in Nigeria regarding Long COVID and provides baseline evidence to inform the development of diagnostic, preventive, and context-appropriate management strategies for the condition.},
}
@article {pmid42416120,
year = {2026},
author = {Colgan, DD and Stadler, DD and Grow, T and Ruddick, M and Weimbs, T and Davenport, TE and Zwickey, H},
title = {Telehealth-Based Ketogenic Metabolic Therapy With Lifestyle Interventions for Post-viral Illness: A Research Brief of Patients' Experiences.},
journal = {Journal of patient experience},
volume = {13},
number = {},
pages = {23743735261459218},
pmid = {42416120},
issn = {2374-3735},
abstract = {BACKGROUND/OBJECTIVES: Infection-associated chronic illnesses are associated with substantial functional impairment that limits participation in traditional in-person research. A fully remote, multicomponent intervention that combines ketogenic metabolic therapy (KMT) with behavioral interventions targets several proposed biological mechanisms underlying these conditions. This study aimed to characterize patient-reported experiences with a fully remote intervention that integrated KMT and thiamine supplementation with behavioral strategies, including circadian entrainment and mindfulness-based resilience coaching.<br><br>METHODS: In this cross-sectional study, quantitative data were collected via online REDCap surveys. Feasibility and acceptability benchmarks included perceived treatment suitability, relevance, safety, and reported treatment adherence. Optimization items evaluated preferred program duration, dosing, and structure, as well as components that respondents identified as most important for future refinement.<br><br>RESULTS: Among an international sample (n=41), all feasibility and acceptability benchmarks were met: 96% reported the intervention was helpful, 96% recommended it, and 75% felt "a lot better" after completion. Respondents provided patient-centered perspectives to optimize the intervention.<br><br>CONCLUSIONS: Incorporating patient perspectives is essential for guiding the development of safe, acceptable, and effective treatment strategies for infection-associated chronic illness, including Long COVID. Strong indicators of feasibility, acceptability, and perceived benefits support the rationale for larger controlled trials to investigate clinical efficacy and the underlying mechanistic pathways of multicomponent metabolic interventions.},
}
@article {pmid42418962,
year = {2026},
author = {Rescalvo-Casas, C and Hernando-Gozalo, M and Lledó-García, L and Cuadros-González, J and Pérez-Tanoira, R},
title = {Prevalence and determinants of long COVID and SARS-CoV-2 reinfection in the Spanish adult population: A nationwide public health survey.},
journal = {Medicina clinica},
volume = {166},
number = {9},
pages = {107491},
doi = {10.1016/j.medcli.2026.107491},
pmid = {42418962},
issn = {1578-8989},
abstract = {INTRODUCTION: Long COVID is an emerging public health concern with heterogeneous prevalence. Evidence on the impact of reinfection and vaccination remains limited, especially in Spain.<br><br>METHODS: We conducted a prospective online cohort survey between January 2024 and April 2025, gathering data on demographics, vaccination, symptoms, comorbidities, and reinfection history from Spanish adults (n=1018). Long COVID was defined per NICE guidelines as symptoms persisting beyond eight weeks after viral clearance. Multivariate logistic regression identified associated factors.<br><br>RESULTS: Of 972 participants (332 men, 640 women), long COVID prevalence was 14.3% (n=139). Female sex (OR: 1.70; 95% CI: 1.10-2.57; p=0.014) and chronic obstructive pulmonary disease (COPD) (OR: 4.14; 95% CI: 1.28-13.42; p=0.018) increased risk. Mixed vaccination schedules raised risk compared to Pfizer-only regimens (OR: 1.30; 95% CI: 1.04-1.62; p=0.020). Reinfection, reported by 47.2%, was also a risk factor (OR: 1.64; 95% CI: 1.12-2.42; p=0.012). Frequent long COVID symptoms included anosmia, dyspnea, pneumonia, and myalgia.<br><br>CONCLUSIONS: This national cohort underscores the persistent burden of long COVID in Spain. Female sex, COPD, reinfection, and mixed vaccination schedules are key associated factors, with implications for targeted prevention strategies and vaccination policies.},
}
@article {pmid42419332,
year = {2026},
author = {Walker, TA},
title = {Building the evidence base for long COVID treatments.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(26)00350-6},
pmid = {42419332},
issn = {1474-4457},
}
@article {pmid42409265,
year = {2026},
author = {Natarajan, N and Ahmed, T and Govindaswamy, B and Manickam, DS and Das, J and Islam, K and Dutta, P},
title = {Macrophage-specific targeting of histone demethylases with small-molecule inhibitors suppresses inflammatory response in vivo.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113315},
doi = {10.1016/j.jbc.2026.113315},
pmid = {42409265},
issn = {1083-351X},
abstract = {Macrophages are versatile immune cells, with the ability to respond to varied intrinsic and extrinsic cues, and transition between inflammatory and pro-reparative phenotypes. A complex network of epigenetic processes, such as DNA methylation, and histone methylation and acetylation, plays key roles in modulating macrophage polarization and inflammatory gene expression. Transcriptional analysis in patients with respiratory failure, long COVID-19, and influenza revealed an augmented expression of chromatin-modifiers including histone demethylases, broadly defined as lysine demethylases (KDMs), in lung macrophages. Therefore, macrophage-specific pharmacological perturbation of these enzymes in vivo holds therapeutic promise in abating inflammation. To investigate the role of KDMs in inflammation, we screened a panel of small-molecule inhibitors of chromatin modifiers for their efficacy in inducing anti-inflammatory macrophage polarization in vitro. We demonstrate that pretreatment with the broad spectrum KDM inhibitor n-octyl-IOX1 and KDM5-specific inhibitor PB-IT resulted in a significant decrease of lipopolysaccharide (LPS)-induced expression of the inflammatory genes Il1b, Il6, Tnfa, and iNos in bone marrow-derived macrophages (BMDM). Subsequent RNA sequencing and CUT&amp;RUN analyses revealed that LPS activation led to distinct transcriptomic and epigenomic alterations including expression of master transcription factors (TFs) BLIMP-1 and GFI1 whereas n-octyl-IOX1 and PB-IT treatments rewired these regulatory networks, thereby impeding inflammatory gene expression and response. To further probe the merit of KDM inhibition in perturbing macrophage-mediated inflammation in vivo, we delivered n-octyl-IOX1 selectively to macrophages in mice using cell-specific, targeted lipidoid nanoparticles. n-octyl-IOX1 encapsulated nanoparticles significantly diminished LPS-mediated peritoneal macrophage expansion and inflammatory gene expression in this cell population, underscoring the importance of macrophage-specific targeting of KDMs with small-molecule inhibitors in inflammatory disease.},
}
@article {pmid42409655,
year = {2026},
author = {Chen, CH and Chen, PC and Liu, XL and Wei, CH and Hsu, YL and Lin, CH and Soong, WJ and Shih-Hsin Wu, L and Tsai, HJ and Chang, SM and Wang, JY},
title = {Post-acute sequelae of COVID in children: Pulmonary assessment using impulse oscillometry and the effect of vaccination.},
journal = {Pediatrics and neonatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pedneo.2026.01.007},
pmid = {42409655},
issn = {2212-1692},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID syndrome (LCS), is characterized by persistent symptoms following SARS-CoV-2 infection and poses significant health challenges, particularly impacting pulmonary function in children. This study aims to evaluate the effect of COVID-19 vaccination on pulmonary function in children with PASC using standardized spirometry and impulse oscillometry (IOS).<br><br>METHODS: This prospective, observational study was conducted from July to September 2022, at the tertiary medical center of a children's hospital in Taiwan. Pediatric patients aged 6 to 18 years diagnosed with PASC were enrolled. Demographic data, vaccination status, and blood test results were collected. Pulmonary function was assessed using spirometry and IOS, measuring parameters such as respiratory resistance (R5, R20) and reactance (X5). Statistical analyses explored the association between IOS results and clinical symptoms, as well as vaccination status.<br><br>RESULTS: Among 209 children, 78.7% were vaccinated. IOS detected abnormalities in 74.6%, with 12.0% diagnosed with obstructive lung disease (OLD) and 62.9% with small airway disease (SAD). Fatigue (56.0%) and dyspnea (52.0%) were most common in OLD, while chest pain (45.0%) and cough (41.7%) prevailed in SAD. Vaccinated children showed significantly lower respiratory resistance (R5, R20, p&#x202f;<&#x202f;0.01) and improved reactance (X5, p&#x202f;<&#x202f;0.001). Vaccination did not significantly reduce respiratory-related symptoms but it was associated with lower risks of decreased appetite (OR&#x202f;=&#x202f;0.399) and sleep disturbance (OR&#x202f;=&#x202f;0.345).<br><br>CONCLUSION: COVID-19 vaccination may have a protective effect on pulmonary function in children with PASC, highlighting its mitigation of long-term respiratory complications. Further studies are needed to explore underlying mechanisms.},
}
@article {pmid42410961,
year = {2026},
author = {Almulla, AF and Zhang, Y and Tunvirachaisakul, C and Carvalho, AF and Maes, M},
title = {Increased Insulin Resistance and Hyperglycemia in Long COVID: A Systematic Review and Meta-Analysis.},
journal = {Expert reviews in molecular medicine},
volume = {},
number = {},
pages = {1-46},
doi = {10.1017/erm.2026.10064},
pmid = {42410961},
issn = {1462-3994},
}
@article {pmid42402140,
year = {2026},
author = {Fésü, D and Horváth, G and Müller, V},
title = {[Long-COVID syndrome and lung-specific abnormalities following COVID-19].},
journal = {Orvosi hetilap},
volume = {167},
number = {27},
pages = {1051-1058},
doi = {10.1556/650.2026.33584},
pmid = {42402140},
issn = {1788-6120},
mesh = {Humans ; *COVID-19/complications/physiopathology ; *Pulmonary Fibrosis/etiology ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *Lung/diagnostic imaging ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Respiratory Function Tests ; },
abstract = {Following the acute phase of a SARS-CoV-2 infection, post-COVID - or long-COVID - syndrome may develop. This condition is characterized by unpleasant, persistent or new-onset symptoms following the acute phase of the infection. It might lead to an impaired health-related quality of life of affected patients and may involve multiple organ systems. It often poses diagnostic and therapeutic challenges for the healthcare system, and its exact course and outcomes are not yet fully understood. A multidisciplinary approach is required for diagnosis, including imaging studies (e.g., chest CT), tests to assess functional status (e.g., 6-minute walk test, pulmonary function tests, cardiopulmonary exercise testing) and the evaluation of parameters reported by patients subjectively (e.g., symptom burden, health-related quality of life). As part of long-COVID, lung parenchymal changes or abnormalities resulting from the viral infection can be detected on imaging studies in some cases, referred as post-COVID pulmonary fibrosis. Currently, therapeutic options are limited and largely based on symptomatic or organ-specific approaches. However, antiviral treatments used in the acute phase, such as remdesivir or nirmatrelvir/ritonavir, may be potentially beneficial regarding the development of late complications. Prevention, particularly COVID-19 vaccination, plays a key role, as it has been shown to reduce the risk of severe acute disease and the later probability of long-COVID syndrome. Further long-term patient follow-up is necessary to better understand the pathomechanisms underlying long-term effects of the virus, such as long-COVID and post-COVID pulmonary fibrosis. This article aims to present an up-to-date, comprehensive review of long-COVID syndrome and post-COVID pulmonary fibrosis. Orv Hetil. 2026; 167(27): 1051-1058.},
}
@article {pmid42402260,
year = {2026},
author = {Jo, Y and Hu, Z and Joo, H and Jung, J and Lee, J},
title = {Time to Recovery from Long COVID: A Longitudinal Analysis of Symptom Duration and Risk Factors Using Accelerated Failure Time Models.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108963},
doi = {10.1016/j.ijid.2026.108963},
pmid = {42402260},
issn = {1878-3511},
abstract = {BACKGROUND: Long COVID comprises heterogeneous symptoms that may persist for months to years after acute SARS-CoV-2 infection. While prevalence is well described, less is known about symptom duration and determinants of recovery.<br><br>METHODS: We conducted a multicenter longitudinal cohort study across 12 institutions in Korea (December 2022-March 2025), enrolling adults with confirmed infection and uninfected controls. Participants were followed for up to 22 months with repeated assessments of symptoms, vaccination, and comorbidities. Eight common symptoms were analyzed. Time to resolution was estimated using Kaplan-Meier methods and log-normal accelerated failure time models, adjusting for demographic and clinical factors. Results are reported as time ratios (TRs).<br><br>RESULTS: Among 757 infected participants and 558 controls, respiratory and physical symptoms resolved similarly between groups, whereas systemic and neurological symptoms persisted longer in infected individuals. At one year, 20-25% reported fatigue and 15-20% sleep disturbance versus &#x223c;10% and &#x223c;5% in controls. Infection was associated with &#x223c;50% longer duration of fatigue and sleep disturbance. Individuals aged 40-59 recovered more slowly; other factors showed minimal associations.<br><br>CONCLUSIONS: Persistent long COVID burden is driven by systemic neuro-related symptoms, highlighting the need for targeted, symptom-specific management strategies.},
}
@article {pmid42403350,
year = {2026},
author = {Dos Santos, ACP and Goulart, CDL and Neves, VR and Milani, M and Silva, E and Almeida-Val, F and Braga, F and Dias, CMCC and Ritt, LEF and Cipriano, GFB and Borghi-Silva, A and Franzoni, LT and Ferrari, F and Cahalin, LP and Stein, R and Cipriano, G},
title = {Regional Disparities in Functional and Socioeconomic Impacts of Long COVID in Brazil: A Cross-Sectional Observational Study.},
journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy},
volume = {31},
number = {3},
pages = {e70251},
doi = {10.1002/pri.70251},
pmid = {42403350},
issn = {1471-2865},
support = {//CAPES, CNPQ and FAPDF/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Brazil/epidemiology ; *COVID-19/physiopathology/epidemiology ; Female ; Post-Acute COVID-19 Syndrome ; Male ; Socioeconomic Disparities in Health ; Middle Aged ; Socioeconomic Factors ; Hand Strength ; Adult ; SARS-CoV-2 ; Severity of Illness Index ; },
abstract = {INTRODUCTION AND OBJECTIVE: In low- and middle-income countries such as Brazil, regional inequalities in healthcare access and socioeconomic conditions may exacerbate the functional and occupational consequences of Long COVID. This study explored between-center differences in functional and socioeconomic outcomes among individuals with Long COVID from three Brazilian centers in Brazil, while examining how these findings may have been influenced by acute disease severity, symptom burden, and contextual factors.<br><br>METHODS: This was a cross-sectional study conducted with individuals diagnosed with Long COVID from three Brazilian regions (Federal District, Goi&#xe1;s, and Sergipe). Functional limitations were assessed through the 6-Minute Step Test (6MST) and muscle strength via Handgrip Strength (HGS). Additionally, cardiorespiratory responses and work productivity impairments were evaluated.<br><br>RESULTS: A total of 142 participants were included: 47 from the Federal District, 59 from Goi&#xe1;s, and 36 from Sergipe. Most participants were classified as non-critical (n&#xa0;=&#xa0;129), while 13 were classified as critical, all from the Federal District. Significant differences in 6MST performance were observed across regions (p&#xa0;<&#xa0;0.005). Critical patients exhibited lower SpO2 at rest and peak compared to non-critical patients from Goi&#xe1;s and Sergipe (mean difference: -4%; 95% CI: -6% to -2%). Non-critical patients from Sergipe had higher peak systolic (+25&#xa0;mmHg; 95% CI: +20 to +30&#xa0;mmHg) and diastolic blood pressure (+16&#xa0;mmHg; 95% CI: +14 to +18&#xa0;mmHg). Critical patients showed work productivity loss (-2.8%; 95% CI: -4.6% to -1.0%) compared to non-critical patients from Goi&#xe1;s. Weak negative correlations were found between peak SpO2 in the 6MST and age (r&#xa0;=&#xa0;-0.25; p&#xa0;=&#xa0;0.01) and between HGS and HADS scores for anxiety (r&#xa0;=&#xa0;-0.20; p&#xa0;=&#xa0;0.05) and depression (r&#xa0;=&#xa0;-0.20; p&#xa0;=&#xa0;0.04).<br><br>DISCUSSION: Long COVID was associated with heterogeneous functional and socioeconomic impairments across the evaluated centers; however, these findings should be interpreted cautiously, as regional comparisons were substantially confounded by the unequal distribution of acute disease severity.},
}
@article {pmid42404887,
year = {2026},
author = {Ponnachan, P and Dhawlarker, A and Yasmin, H and Shah, A and Malhotra, A and Shastri, A and Al-Ramadi, BK and Kishore, U},
title = {Mechanisms and impact of long COVID: pathophysiology, neuropsychiatric effects and vaccination.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1710777},
pmid = {42404887},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/physiopathology/psychology/complications/prevention &amp; control ; Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; Vaccination ; Mental Disorders/etiology ; },
abstract = {Long COVID or post-acute sequelae of COVID-19 is defined as an after-effect of acute COVID-19 infection. Its broad clinical symptoms include brain fog, shortness of breath, fatigue, joint, chest, or muscle pain, dysautonomia and neuropsychiatric symptoms such as anxiety, depression and post-traumatic stress disorder. It is estimated that 1 in every 5 COVID-19 survivors exhibit symptoms within the Long COVID bracket. An array of risk factors such as smoking habit, age, obesity, female sex, and prior hospitalization may increase the probability of a person developing Long COVID. While the underlying mechanisms of Long COVID remain elusive, we examine the various possible pathophysiologies involved in Long COVID. We take up impactful neuropsychiatric issues as another spectrum of Long COVID symptoms and the likely effect of various forms of COVID-19 vaccines. In this review, the focus will be on the main mechanisms associated with the development of long COVID, which include latent Epstein-Barr virus reactivation, molecular mimicry, virus persistence, autoantibodies, and mitochondrial dysfunction. Understanding these mechanisms shed light on the continued persistence of COVID-19 related symptoms long after the resolution of acute infection. For instance, the reactivation of Epstein-Barr virus in the immunocompromised context seen post-acute SARS-CoV-2 infection could lead to the symptoms commonly observed in Long COVID such as fatigue and brain fog. The Epstein-Barr virus could possibly disrupt mitochondrial function, explaining the fatigue commonly observed in Long COVID patients. Other factors such as continued presence of viral particles in specific areas such as the gut may result in continued inflammation, leading to manifestations such as fatigue, cognitive impairment and gastrointestinal dysfunction. Additionally, heightened and persistent presence of autoantibodies post-acute infection results in persistent symptoms and could potentially trigger the onset of autoimmune disorders. We also aim to revisit the diverse and prolonged effects of the COVID-19 pandemic that continue to affect the well-being and quality of human life.},
}
@article {pmid42406565,
year = {2026},
author = {Mugwagwa, T and Marcano Belisario, J and Hartley, L and Phan, NTN and Mokgokong, R},
title = {Evaluation of nirmatrelvir/ritonavir treatment for COVID-19 on health-related outcomes: a global economic value systematic literature review.},
journal = {Journal of medical economics},
volume = {29},
number = {1},
pages = {1875-1897},
doi = {10.1080/13696998.2026.2695551},
pmid = {42406565},
issn = {1941-837X},
mesh = {*Ritonavir/therapeutic use/economics ; Humans ; *COVID-19 Drug Treatment ; Cost-Benefit Analysis ; Quality-Adjusted Life Years ; *Antiviral Agents/economics/therapeutic use ; Cost-Effectiveness Analysis ; Drug Combinations ; COVID-19 ; SARS-CoV-2 ; Lopinavir ; },
abstract = {AIMS: Nirmatrelvir/ritonavir (NMV/r)[i] is an antiviral drug indicated for the treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk of progressing to severe disease. We performed an updated economic systematic literature review (eSLR) of NMV/r to build upon evidence reported in our previous eSLR and additionally examine the health-related outcomes associated with NMV/r and any potential effect of long COVID.<br><br>METHODS: A systematic search of Embase, PubMed, Cochrane, and EconLit and of conference and health technology assessment agency websites was performed to identify economic analyses published between January 2022 and October 2025.<br><br>RESULTS: Of the 33 included economic evaluations, most were cost-utility analyses (n&#x2009;=&#x2009;16) and used an analysis of a short-term decision tree with a long-term Markov model (n&#x2009;=&#x2009;11). Several types of health-related endpoints were reported by studies, with most including hospital-related endpoints (n&#x2009;=&#x2009;20), quality-adjusted life-years (QALYs) (n&#x2009;=&#x2009;18), and death-related endpoints (n&#x2009;=&#x2009;18). Positive health-related outcomes were associated with NMV/r treatment, including reductions in hospitalizations and deaths and an increase in QALYs. NMV/r treatment was also associated with a reduced number of patients with long COVID complications.<br><br>LIMITATIONS: Most studies were conducted in high-income countries, were based on different COVID-19 variants, and were limited in data on the long COVID population.<br><br>CONCLUSION: In addition to monetary benefits, NMV/r provides short-term and long-term health-related benefits to patients with mild to moderate COVID-19. This study provides further support for NMV/r as a cost-effective treatment option.},
}
@article {pmid42409185,
year = {2026},
author = {Nehme, M and Hund-Georgiadis, M and Corral Beamonte, ED and Bridevaux, PO and Hoepner, R and Penner, IK and Strobel, J and Fretz, G and Rovira, MB and Puchades, F and Landi, F and Vasco, PG and Guaraldi, G and Cordero, FM and Sebastianelli, L and Sarmati, L and Berthuy, N and Wojcik, J and Keddad, K and Post, A and Leppert, D and Guessous, I},
title = {Temelimab versus placebo in patients with post-COVID condition.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106892},
doi = {10.1016/j.bbi.2026.106892},
pmid = {42409185},
issn = {1090-2139},
abstract = {INTRODUCTION: More than 400 million individuals are estimated to have been affected by post-COVID condition or long COVID. This condition can lead to significantly decreased quality of life and increased individual and societal costs. Temelimab, a monoclonal IgG4 backbone antibody targeting HERV-W ENV, may be a potential treatment for post-COVID.<br><br>METHODS: In this randomized, double-blind trial, which consisted of a 24-week treatment period, we enrolled adults who had fatigue and persistent symptoms due to post-COVID and were positive for HERV-W-ENV. Participants were randomized (1:1) to receive 54&#x202f;mg/kg Temelimab or placebo IV once monthly. The primary endpoint was the decline in fatigue (defined as a 3-point decrease on the PROMIS Fatigue SF 7a scale) from baseline to Week 24. Secondary endpoints included changes in cognition, anxiety, depression, functional impairment, quality of life, safety and tolerability of Temelimab.<br><br>RESULTS: A total of 203 individuals participated in this study, 72% women, mean age 46 (standard deviation, SD 10) years. The mean initial PROMIS Fatigue SF 7a score was 26.8 (SD 3.4) in the Temelimab group and 27.1 (SD 3.8) in the placebo group. At 24&#x202f;weeks, there was no difference between Temelimab (3.2 points decrease in the PROMIS score) and placebo (3.8 points decrease). Secondary outcomes also did not show differences between the Temelimab and placebo groups.<br><br>CONCLUSION: In adults with persistent symptoms due to post-COVID condition, the use of Temelimab did not show improvement in fatigue compared to placebo (Funded by GeNeuro SA; ClinicalTrials.gov number NCT05497089).<br><br>ETHICS AND DISSEMINATION: National authorities for clinical trials on medicinal products and ethical approval was obtained in all participating countries in Europe. Trial registration numbers ClinicalTrials.gov number (NCT05497089), EudraCT (2022-000618-32). Protocol version v5.0, date 23 February 2024; CCER Geneva IRB: 2022-00658.},
}
@article {pmid42399853,
year = {2026},
author = {Cheshire, A and Cartwright, T},
title = {Perceptions, acceptability and experiences of yoga to support long-COVID: a survey of people living with long-COVID.},
journal = {BMC complementary medicine and therapies},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12906-026-05430-2},
pmid = {42399853},
issn = {2662-7671},
abstract = {BACKGROUND: The impact of long-COVID can be substantial for individuals, health systems and the economy, nevertheless, treatment and support options are limited. Yoga offers a potential solution to reduce the burden of long-COVID, demonstrating positive impacts on the biological mechanisms implicated in long-COVID, key long-COVID symptoms and associated mental health challenges. Yoga interventions can also be designed for people with limited physical ability, and online delivery can increase accessibility.<br><br>AIM: To understand the perceptions and experiences of yoga among people with long-COVID (PWLC), and assess its potential benefits.<br><br>METHODS: An online survey of PWLC, comprised closed and open response questions on: long-COVID symptoms, support needs, perceptions of a yoga intervention and its components and yoga use. Participants (n&#x2009;=&#x2009;171) were recruited via Prolific. Inclusion criteria were long-COVID (formal diagnosis or self-reported) and living in the UK. Inductive thematic analysis was used for open ended responses.<br><br>RESULTS: Analysis identified unmet needs among PWLC that align with the potential benefits of a yoga intervention, particularly in supporting symptom management, self-management and associated psychological symptoms. Additionally, a yoga intervention could provide acknowledgment and support to PWLC who feel despondent about their condition and abandoned by health professionals. Participants reported a high level of interest in a yoga intervention, perceiving it could be of benefit. Barriers to yoga practise included anxiety regarding the group setting, fitting sessions into schedules, lack of energy and concerns about suitability for long-COVID. Those already practising yoga with long-COVID reported that yoga helped to manage symptoms and associated psychological challenges, as well as increasing flexibility and providing a safer alternative to exercise.<br><br>CONCLUSIONS: Many PWLC have positive perceptions of yoga and there is a good level of interest in a yoga intervention among this population. These findings suggest that yoga is a suitable intervention for study in future research as well as delivery in the community by qualified yoga instructors with a knowledge of long-COVID - provided that any intervention is appropriately tailored to fit the ability and address the concerns of PWLC. It should be offered in the context of health professional validation of symptoms.},
}
@article {pmid42401313,
year = {2026},
author = {Lkhagvasuren, B and Suematsu, T and Xiangyu, L and Hata, T and Takakura, S and Hiramoto, T and Oka, T and Sudo, N},
title = {Chronic stress primes TLR3-mediated systemic inflammation to produce persistent post-viral fatigue syndrome-like symptoms in mice.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.07.002},
pmid = {42401313},
issn = {1873-7544},
abstract = {BACKGROUND: This study examined the long-term effects of polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA and Toll-like receptor 3 (TLR3) agonist, on behavioral and immune outcomes in chronically stressed mice.<br><br>METHODS: Male C57BL/6J mice were exposed to 21&#x202f;days of wet bedding stress followed by a poly I:C injection. Post viral fatigue syndrome (PVFS)-like symptoms were evaluated over 7&#x202f;days post-injection using grip strength testing, the forced swim test, von Frey filament testing, the Morris water maze, the open field test, and the social interaction test. Body temperature and locomotor activity were continuously monitored via intraperitoneally implanted dataloggers. Serum concentrations of interleukin-6 (IL-6), IL-10, and C-X-C motif chemokine ligand 10 (CXCL10) were quantified. In separate cohorts, minocycline (a microglial activation inhibitor) or RU486 (a glucocorticoid receptor antagonist) was administered prior to poly I:C injection.<br><br>RESULTS: Following IP injection of poly I:C, body temperatures in both stressed and unstressed mice were significantly elevated, indicating a polyphasic febrile response. At 7&#x202f;days post-injection, stressed mice treated with poly I:C exhibited persistent fatigue, mechanical allodynia, depressive-like behavior, impaired spatial memory, increased anxiety-like behavior, and reduced social interaction. Serum levels of IL-6 and CXCL10 remained elevated and correlated with behavioral outcomes. Pretreatment with minocycline partially attenuated both the behavioral and immune responses, whereas RU486 pretreatment did not.<br><br>CONCLUSION: These findings demonstrate that TLR3-mediated systemic inflammation induced by poly I:C produces persistent, multi-domain PVFS-like symptoms in chronically stressed mice. The attenuation by minocycline implicates neuroinflammation as a possible mechanism.},
}
@article {pmid42402067,
year = {2026},
author = {Mullard, J},
title = {Long COVID: Lived Experiences, Diagnosis, Treatment and Care.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {4},
pages = {e70757},
doi = {10.1111/hex.70757},
pmid = {42402067},
issn = {1369-7625},
}
@article {pmid42399828,
year = {2026},
author = {Appel, S and Coughtrey, AE and Kyrdalen, A and Takeda, A and Newlands, F and Stephenson, T and Shafran, R and Pereira, SMP},
title = {Understanding heterogeneity in paediatric long COVID research: an overview of reviews and recommendations for future pandemics.},
journal = {BMC pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12887-026-07276-6},
pmid = {42399828},
issn = {1471-2431},
abstract = {BACKGROUND: Studies of Long COVID or Post-COVID-19 condition in children and young people have varied considerably in their reported prevalences. We aimed to examine the methodological heterogeneity underlying this variability and explore whether methodological characteristics were correlated with reported Long COVID outcome prevalence, in order to inform recommendations to improve reporting in future pandemic-related epidemiological research.<br><br>METHODS: We conducted an overview of reviews with a narrative synthesis, identifying systematic reviews and meta-analyses and extracting their included primary studies. We identified reviews of Long COVID in children &amp; young people in PubMed and Embase using a systematic search strategy. We extracted key methodological details including study design, sample size, sample and control group characteristics, data collection and reporting methods, as well as time-point(s) of surveying and frequency of follow-up. We explored correlations between these factors and prevalence of Long COVID via Spearman's rank correlation coefficients or the Kruskal-Wallis test.<br><br>RESULTS: 69 studies, from identified reviews, met the inclusion criteria with outcome symptom prevalence varying between 0 and 90% at >&#x2009;3-months post-COVID-19 infection. Only 19% of studies used an established Long COVID definition to guide analyses. There was substantial heterogeneity in the design and outcome reporting of Long COVID studies. We did not find Long COVID prevalence varied by examined methodological factors (p&#x2009;&#x2265;&#x2009;0.08 for all correlations).<br><br>CONCLUSION: While substantial methodological heterogeneity was observed across studies of paediatric Long COVID, no statistically significant correlations were identified between examined methodological factors and reported prevalence. Such variability limits comparability across studies and highlights the need for more standardised definitions, outcome measures, and reporting approaches in future pandemic-related epidemiological research: we discuss reporting guidelines and recommendations for future paediatric epidemiological research during a pandemic.},
}
@article {pmid42391726,
year = {2026},
author = {Kaplan, G},
title = {Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.},
journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis},
volume = {65},
number = {4},
pages = {104482},
doi = {10.1016/j.transci.2026.104482},
pmid = {42391726},
issn = {1473-0502},
abstract = {Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions. This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.},
}
@article {pmid42392788,
year = {2026},
author = {Yan, X and Tang, X and Zhang, YZ and Liu, YY and Liu, Y and Pang, WT and Yang, FW and Jin, XY},
title = {[Status analysis of clinical outcome for treatment of long COVID with traditional Chinese and western medicines].},
journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica},
volume = {51},
number = {7},
pages = {2081-2091},
doi = {10.19540/j.cnki.cjcmm.20251125.501},
pmid = {42392788},
issn = {1001-5302},
mesh = {Humans ; COVID-19 ; Post-Acute COVID-19 Syndrome ; *Drugs, Chinese Herbal/therapeutic use ; SARS-CoV-2/physiology/drug effects ; *COVID-19 Drug Treatment ; *Medicine, Chinese Traditional ; Treatment Outcome ; Pandemics ; *Coronavirus Infections/drug therapy ; },
abstract = {This study sorted out the clinical outcome of traditional Chinese and western medicines in the treatment of long COVID to lay the foundation for the construction of a core indicator set. Search was made on some databases and platforms from their inception to December 2024, which included eight databases of CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane Library, EMbase, and Web of Science and three clinical research protocol registration platforms, namely the Chinese Clinical Trial Registry(ChiCTR), the International Traditional Medicine Clinical Trial Registry(ITMCTR), and the American Clinical Trial Registry(ClinicalTrials.gov). Two researchers independently extracted the basic information, outcomes, measurement time points, and measurement tools of literature in parallel according to the inclusion and exclusion standards. If there are any differences, a third researcher would make discussions and decisions. A total of 152 studies, including 50 literature studies and 102 protocol studies, were ultimately included. A total of 338 outcomes indicators were reported, with a reporting frequency of 1 633 times. Outcome indicators can be classified into 10 indicator domains based on attributes, including symptoms and signs(694 times, 42.50%), TCM diseases(61 times, 3.74%), security incidents(93 times, 5.70%), etiological detection(23 times, 1.41%), long-term prognosis(72 times, 4.41%), economic indicators(14 times, 0.86%), physical and chemical testing(472 times, 28.90%), quality of life(173 times, 10.59%), major events(16 times, 0.97%), and other indicators(15 times, 0.92%). There were problems in the outcomes indicators of treating long COVID with both traditional Chinese and western medicines, such as significant differences in symptom descriptions, lack of standardization in indicator selection, diverse choices of measurement tools, diverse selection of measurement time, lack of practicality in clinical practice, and non-prominent TCM indicators. These issues led to scattered evidence and the absence of a unified core indicator set to guide clinical research. Further efforts are needed to develop COS of integrated traditional Chinese and western medicine treatments for long COVID, and to enhance the quality of clinical research on long COVID.},
}
@article {pmid42393618,
year = {2026},
author = {Guan, N and Turner, G and Hotham, R and Lange, D and Brown, KR and McMullan, C and Hughes, SE and Aiyegbusi, OL and Matthews, K and Jackson, L and Yahyouche, A and Alder, Y and Jeyes, F and Buckland, L and Chong, A and Stanton, D and Calvert, M and Haroon, S},
title = {Self-management of long COVID symptoms with over-the-counter medicines and other non-prescribed therapies: a cross-sectional survey.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-28017-5},
pmid = {42393618},
issn = {1471-2458},
support = {COV-LT-0013//National Institute for Health and Care Research/ ; COV-LT-0013//UK Research and Innovation/ ; },
abstract = {BACKGROUND: The high prevalence of long COVID globally necessitates investigation into its self-management, especially given the absence of definitive and effective treatments and uneven access to healthcare services.<br><br>METHODS: This study surveyed the use of over-the-counter (OTC) medicines, supplements, remedies, and other non-prescription therapies for managing long COVID symptoms in the UK. It aimed to identify the range of treatments used for self-management, explore the sources of these treatments, factors influencing treatment choices, and associated out-of-pocket expenses. A cross-sectional electronic survey was provided to individuals experiencing long COVID. It included questions on the use of OTC medications, supplements, and other therapies, where they were sourced, decision-making influences, and financial costs. Descriptive statistics and thematic analysis were applied to analyse the data.<br><br>RESULTS: Among the 193 surveyed participants, significant use of vitamins, minerals, and herbal treatments (88.8%), and analgesics (73.6%) was reported, with 42% exceeding recommended dosages. Some participants sought relief through alternative therapies such as physiotherapy and acupuncture, often incurring significant personal expenses. Choices about self-management were influenced by medical professionals, family, friends, and online sources, including support groups and social media.<br><br>CONCLUSIONS: People with long COVID may access a wide range of OTC medicines, dietary supplements, herbal remedies, and non-pharmacological therapies to self-manage symptoms. Healthcare providers should be aware of the use of non-prescribed therapies among long COVID sufferers and consider these in their treatment plans. Public health policies should focus on providing accurate information and guidance for patients self-managing long COVID symptoms.},
}
@article {pmid42395315,
year = {2026},
author = {Turebekova, D and Kosherova, B and Dauletkaliyeva, Z and Shayakhmetova, Y and Marchenko, A and Solyanov, D and Hendrixson, V and Kadyrova, I},
title = {Long COVID and health-related quality of life: a systematic review of immune, inflammatory, and metabolic markers.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1846407},
pmid = {42395315},
issn = {2296-2565},
mesh = {Humans ; *Quality of Life ; Biomarkers/blood ; *COVID-19/immunology ; *Inflammation/immunology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID is known to be associated with prolonged multiple organ symptoms and decreased health-related quality of life (HRQoL), but the pathogenesis and relationship between immune, inflammatory, and metabolic biomarkers and HRQoL remains poorly understood. This systematic review aims to synthesize the evidence on the health-related quality of life of patients with Long COVID and to summarize the reported associations between health-related outcomes and biomarkers.<br><br>METHODS: We conducted a systematic search in PubMed, Web of Science, and Scopus in search of studies that evaluated immune, inflammatory, or metabolic biomarkers and HRQoL in patients with Long COVID. This review included case-control and cohort studies with a control group. The Rayyan tool was used to select studies, and full-text articles were evaluated for compliance with the criteria. Information was obtained on biomarkers, analytical methods, tools for assessing the HRQoL, and the relationship between HRQoL and biomarkers. Due to the high heterogeneity of the methods, the results were summarized in a descriptive form.<br><br>RESULTS: Ten studies were included, involving 1,078 patients with Long COVID and 768 healthy controls. Most studies that used various methods to assess HRQoL consistently reported long-term deterioration after COVID, with the greatest deterioration observed in the areas of physical functioning, vitality, fatigue, daily activities, pain, discomfort, and respiratory distress. The most frequently measured markers were related to inflammation and endothelial/coagulation pathways, including CRP, hsCRP, IL-6, TNF-&#x3b1;, D-dimer, and VCAM-1. Autoimmune, metabolic, intestinal barrier, and omics-based markers were measured less frequently, but indicated phenotype-specific biological heterogeneity. Only a few studies have identified a direct link between biomarkers and HRQoL. Lower HRQoL indicators were associated with increased neurotoxicity, decreased calcium levels, systemic inflammation, endothelial dysfunction, and signals from individual autoantibodies.<br><br>CONCLUSION: Our results indicate that Long COVID is consistently associated with a long-term decline in HRQoL, especially in the physical and functional areas. The available data indicate the presence of a strong signal regarding inflammatory processes and endothelial coagulation, while autoimmune, metabolic, and genetic data indicate phenotype-specific heterogeneity.<br><br>Unique identifier: CRD420251239371, URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251239371.},
}
@article {pmid42396378,
year = {2026},
author = {Murlimanju, BV and Shenoy, MP and Ullal, SD and Vadgaonkar, R},
title = {Perception of body donation among the Phase-1 medical students, a questionnaire-based study.},
journal = {F1000Research},
volume = {15},
number = {},
pages = {133},
doi = {10.12688/f1000research.175620.3},
pmid = {42396378},
issn = {2046-1402},
mesh = {Humans ; *Students, Medical/psychology ; Female ; Cadaver ; Surveys and Questionnaires ; Male ; Cross-Sectional Studies ; *Tissue and Organ Procurement ; *Health Knowledge, Attitudes, Practice ; Young Adult ; Adult ; COVID-19 ; },
abstract = {BACKGROUND: This study aimed to examine the knowledge, attitude, and perception of body donation among Phase-1 medical students at our institution. The objectives were to assist teachers in providing insight into the perception of this among students.<br><br>METHODS: This was a cross-sectional, institution-based, time-bound study comprising 29 validated questions regarding comprehensive aspects of body donation. There were 396 medical students in Phase-1 from admissions for two consecutive years.<br><br>RESULTS: Most students (94.4%) were aware of the source of cadavers in the dissection hall, which were either donated or unclaimed bodies from the hospital. However, 38.9% of them were unaware of the guidelines for body donation, and 79% were ignorant of the documents required to pledge. However, 84.3% were aware that it was mandatory to sign a pledge form. The time frame to procure the dead body to the department of anatomy of the institution was not known to 79% of the participants, and 93.2% of the participants opined that corpses from other neighboring states could be accepted. Opinions regarding the acceptance of donated bodies afflicted with long COVID were supported by 218 (55.1%), not supported by 47 (11.9%), and neutral by 131 (33.1%) participants in this study.<br><br>CONCLUSION: Specific knowledge gaps were encountered, including the timeframe, logistics, and legal issues in procuring the body. Since medical students play an important role in this societal motivation, it is suggested that a scientific session be planned in the curriculum of Phase-1 regarding the protocol of body donation. Apart from providing insights, this study also accomplishes the United Nations' sustainable development goal-4 in offering quality medical education. This study, apart from providing insights, also accomplishes the United Nation's sustainable development goal-4 in offering quality medical education.},
}
@article {pmid42396494,
year = {2026},
author = {Tasnim, H and Forrest, S and Hofmeyr, S and Friedman, A and Etemadpour, R and Andrews, A and Cannon, J and Moses, M and Mehdikhani, H},
title = {Spatial Immune Model of Alveolar Lung Infection (SIMALI) Identifies Structural Determinants of Lung Inflammation.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9986593/v1},
pmid = {42396494},
issn = {2693-5015},
abstract = {Inflammation and lung damage in response to respiratory viral infection is a major cause of morbidity and mortality. How specialized lung alveolar structures contribute to variation in inflammatory lung damage observed in patients is a gap in current knowledge. Filling this gap is important for understanding how respiratory infections can lead to persistent and chronic sequelae after acute viral infection, including post-acute sequelae of COVID-19, or "long COVID". Few computational models have incorporated the spatial complexity of alveolar sacs, key sites where infection and inflammation damage lung function. We propose a novel computational model, SIMALI, which represents a sample of the lung's alveolar space as a structured 3D lattice of alveoli composed of air and epithelial cells surrounded by structural lung tissue through which virus and inflammation diffuse. SIMALI extends a previous agent-based model by adding key structural components of the lung, including physiological percentages of infectable cells and differential diffusion of virus through air and lung tissue. SIMALI's simulation predictions are validated against the spatial-temporal growth of lung lesions from Computed Tomography (CT) scans of patients with SARS-CoV-2 infection. By combining parameters validated in a prior study with alveolar structure, the model accurately predicts the typical growth of lung inflammation observed in patient CT scans. SIMALI demonstrates how the spatial architecture of alveolar sacs and the distribution of infectable cell types in the lung constrain the spread of virus and inflammation. Furthermore, SIMALI simulations show how the initial deposition of foci of viral infection distributed across alveolar sacs is an important mechanistic cause of variation in lung damage due to inflammation. The spatial SIMALI model demonstrates a key role for the structure of the alveolar space in driving inflammatory responses. Lung alveolar structure, combined with variation in immune response and the amount and location of initial viral deposition in the lung, all contribute to the highly variable damage to lung recapitulating variation observed across patients with SARS-CoV-2 infection.},
}
@article {pmid42398146,
year = {2026},
author = {Hackshaw, KV and Osuna-Diaz, MM and Sebastian, KR and Nuguri, SM and Castellvi, SL and Yu, L and Mikulik, Z and Giusti, MM and Brode, WM and Rodriguez-Saona, L},
title = {Symptom, functional, and medication overlap between long COVID and fibromyalgia.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {81},
number = {},
pages = {101046},
doi = {10.1016/j.clinsp.2026.101046},
pmid = {42398146},
issn = {1980-5322},
abstract = {BACKGROUND: Long COVID (LC/PASC) and Fibromyalgia (FM) share prominent pain, fatigue, and cognitive symptoms and are often difficult to distinguish clinically. The authors compared LC/PASC and FM using harmonized questionnaires assessing symptoms, function, and medication burden to quantify phenotype overlap and inform biomarker development.<br><br>METHODS: The authors analyzed a harmonized dataset including LC/PASC participants and FM-only comparators. Measures included age, sex, BMI, FIQR/SIQR-equivalent, BDI, CSI, MPQ, VAS pain, medication burden derived from free-text entries, and descriptive SF-36 domains.<br><br>RESULTS: The sample included 54 LC/PASC and 889 FM-only visits. LC/PASC participants were older and less often female. Across symptom and function measures, partial overlap was observed, with domain-specific differences. Medication burden was common; FM showed greater centrally acting medication use. SF-36 domains showed broad similarity with domain-specific differences.<br><br>CONCLUSIONS: In this preliminary, hypothesis-generating comparison, LC/PASC and FM demonstrate partial and domain-specific overlap across questionnaire measures, while differences in medication exposure may influence symptom reporting and limit direct clinical comparisons. These findings support the need for prospective studies integrating objective biomarkers with standardized clinical phenotyping.},
}
@article {pmid42382648,
year = {2026},
author = {Chipol-Ceja, RL and Morales-Romero, J and Rivero-López, CA and Pérez-Callejas, MDS and López-Ortiz, G and Del Carpio-Orantes, L and Spinoso-Torres, CI and González-Periañez, S and Rodríguez-Cordoba, MJ and Ovando-Diego, L and Zurutuza-Lorméndez, JI},
title = {SARS-CoV-2 reinfection: a possible contributing factor to long COVID in children and adolescents.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1691052},
pmid = {42382648},
issn = {2296-2360},
abstract = {BACKGROUND: Following the end of the COVID-19 pandemic, attention shifted towards patients who developed sequelae, persistent symptoms, or relapsing or remitting symptoms of new conditions after a prior history of acute SARS-CoV-2 infection. The objective of the present study was to identify the prevalence, clinical characteristics, and potential associated factors of long COVID in children treated during the pandemic in a primary care unit.<br><br>METHODS: A cross-sectional analytical study was conducted from January to December 2022. Children under 18 years of age and their parents were included in the study if they had been treated at the Mexican Social Security Institute. Two distinct manifestations of long COVID were considered: (a) "persistence", defined as continuous symptoms beginning in the acute phase and lasting for more than 3 months; and (b) "post-COVID conditions", defined as new or recurrent symptoms lasting for more than 3 months, appearing after the acute episode, and not associated with any active disease or infectious condition. An exploratory binary logistic regression analysis was performed to identify associated factors, using an odds ratio (OR) as the measure of association.<br><br>RESULTS: The study included 349 children and adolescents. The prevalence of long COVID was 11.8% (95%CI 7.8%-17.5%). For "persistence", the most frequent symptoms were cough (50%) and rhinorrhea (15.4%); for "post-COVID conditions", the most common symptoms were myalgia (33.3%), asthenia and irritability (26.7% each), and constipation (20%). Multivariate analysis revealed that the associated factors for individuals aged over 8 years were a history of reinfection (OR 9.7, 95%CI 1.6-58) and BMI at the time of the survey (OR 1.1, 95%CI 1.0-1.2), while for those aged under 8 years, the associated factor was male sex (OR 4.7, 95%CI 1.3-17.3). It is important to emphasize that these results are the product of an exploratory analysis and aim to create and test new hypotheses.<br><br>CONCLUSIONS: For healthcare professionals, it is crucial to consider the possibility of long COVID, as this study indicated that approximately 12% of children and adolescents may be affected. Further research is necessary to better understand and manage long COVID in pediatric populations and to investigate the association between reinfections and their increased prevalence.},
}
@article {pmid42384384,
year = {2026},
author = {Vanova, M and Patel, AMR and Scott, I and Gilpin, G and Manning, EN and Ash, C and Wittenberg, P and Lim, J and Hoare, Z and Evans, R and Bray, N and Kipps, CM and Devine, C and Ahmed, S and Dunne, R and Koniotes, A and Warren, C and Chan, D and Suarez-Gonzalez, A},
title = {Cognitive Rehabilitation and Functional Outcomes in Long COVID-Related Cognitive Impairment: A Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {9},
number = {7},
pages = {e2620687},
doi = {10.1001/jamanetworkopen.2026.20687},
pmid = {42384384},
issn = {2574-3805},
mesh = {Humans ; Female ; Middle Aged ; *COVID-19/complications/psychology ; Cognitive Training ; Male ; *Cognitive Dysfunction/rehabilitation/etiology ; Single-Blind Method ; Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Treatment Outcome ; Cognitive Enhancement ; },
abstract = {IMPORTANCE: Cognitive impairment is common in long COVID and severely affects daily life, with no proven treatments to date.<br><br>OBJECTIVE: To evaluate the ability of cognitive rehabilitation (CR) to improve goal attainment, cognitive, and clinical outcomes in individuals with cognitive impairment as part of long COVID.<br><br>This multicenter, single-blind, 2-arm, parallel-group randomized clinical trial was conducted at 3 sites in England between February 2023 and March 2024. Participants were adults aged 30 to 60 years with prior COVID-19 infection and objective cognitive impairment (&#x2265;1 SD below age norm in &#x2265;2 cognitive domains). A sample size of 88 participants (44:44) was required to detect a conservative effect of 0.7 on the goal attainment score at 3 months.<br><br>INTERVENTIONS: Participants were randomized (1:1) to CR or treatment as usual (TAU). CR consisted of 10 individual 1-hour sessions conducted once per week with a trained researcher, applying evidence-based strategies to 3 individually selected, personally meaningful functional goals. TAU was variable, with most participants having access to specialist memory clinics.<br><br>MAIN OUTCOME AND MEASURES: The primary outcome consisted of participant-reported goal-attainment scores at 3 months after randomization measured by the Bangor Goal-Setting Interview. Analysis was conducted on an intention-to-treat basis using multilevel mixed-effects models with 2-sided 95% CIs and 5% significance.<br><br>RESULTS: A total of 78 participants (24 male [30.8%] and 54 female [69.2%]; mean [SD] age, 47.3 [7.2] years) were randomized, including 38 individuals in CR and 40 individuals in TAU groups. At 3 months after randomization, goal attainment was significantly greater in the CR compared with the TAU group (adjusted mean difference, 2.88 [95% CI, 2.03-3.73]; P&#x2009;<&#x2009;.001; Cohen d&#x2009;=&#x2009;1.57), with CR providing a large and clinically meaningful treatment effect. This was sustained at 6 months, with a lower effect size (adjusted mean difference, 1.72 [95% CI, 0.86-2.57]; P&#x2009;<&#x2009;.001; Cohen d&#x2009;=&#x2009;0.91).<br><br>CONCLUSIONS AND RELEVANCE: In this study, individualized, goal-oriented CR led to significant and sustained improvements in goal attainment in people with long COVID-related cognitive impairment. These findings may guide and inform the provision of CR treatments and services for people living with long COVID.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05731570.},
}
@article {pmid42389520,
year = {2026},
author = {Nicaise, C and Bulpa, P and Jamoulle, M},
title = {Autoantibody-mediated pain in long COVID: evidence from multiple lines.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1840110},
pmid = {42389520},
issn = {1664-3224},
}
@article {pmid42376966,
year = {2026},
author = {Rhodes, T and Cowan, H and Clarke, Z and Fernes, P and Mcfarland, S and Ward, H},
title = {Young People Navigating the Looping Effects of Long Covid: Exhausting Agency and the 'Ongoing After' of Pandemic.},
journal = {Sociology of health &amp; illness},
volume = {48},
number = {6},
pages = {e70210},
pmid = {42376966},
issn = {1467-9566},
support = {135315//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *COVID-19/psychology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Adolescent ; Female ; Male ; SARS-CoV-2 ; Qualitative Research ; Social Support ; Young Adult ; *Coronavirus Infections/psychology ; *Pneumonia, Viral/psychology ; },
abstract = {Seeing beyond the COVID-19 pandemic as an extraordinary spectacle situated in the past, we draw on qualitative research with young people to trace experiences of Long Covid as 'looping effects' of entangling physical and social impacts which intersect with, and extend, those of pandemic. Navigating the capacity to do ordinary things becomes highly contingent, and exhausting work, in the face of Long Covid. The physical impacts of illness, including fatigue, are materialised in altering biographical and social relationships, and managing the 'social life' of Long Covid is a key concern. The lifetimes of Long Covid and pandemic also feed into one another. Configurations of the COVID-19 pandemic as a thing of the past, and social responses felt discounting of the Long Covid experience, enact ongoing illness as 'out of sync', and contribute as elements of exhausted agency and extended precarity. The social impacts of the pandemic looping with Long Covid become iterations without clear end; events ongoing in the living present. Understanding how Long Covid extends the 'ongoing after' of pandemic highlights the need for lasting social support for affected young people.},
}
@article {pmid42377750,
year = {2026},
author = {Floridia, M and Weimer, LE and Palange, P and Ciardi, MR and Rovere-Querini, P and Bonfanti, P and Tosato, M and Barisione, E and Lacedonia, D and Gnerre, P and Parati, G and Onder, G and , },
title = {Factors affecting exercise performance at the 6-min walk test in long-COVID: a multicenter study from Italy.},
journal = {Internal and emergency medicine},
volume = {},
number = {},
pages = {},
pmid = {42377750},
issn = {1970-9366},
support = {I85F21003410005//Ministero della Salute/ ; },
abstract = {The cofactors potentially affecting exercise performance after COVID-19 are still incompletely investigated. The contribution of several clinical and demographic variables to the exercise capacity measured with the 6-min walk test was assessed in multivariable analyses that used the absolute distance walked in 6 min (6MWD) and an impaired performance (6MWD < 60% of the predicted value) as study outcomes. The variables considered were age, sex, preexisting comorbidities, COVID-19 severity, pandemic phase, treatments administered in acute phase, SARS-CoV-2 vaccination, reinfection, time from acute infection, and presence of 30 persisting symptoms. The mean 6MWD recorded among 686 patients at a mean interval of 184 days from COVID-19 was 474 m, with 8.3% of them presenting values below 60% of the predicted value. 6MWD was affected by sex, comorbidities, COVID-19 severity, and some persisting symptoms. The estimated effect sizes were -29.9 m for severe/critical acute disease, between -26 and -87 m for six comorbidities (atrial fibrillation, renal failure, chronic liver disease, chronic pulmonary disease, ischemic heart disease, diabetes) and between -21 and -99 m for four persisting symptoms (nausea/vomiting, paresthesia, depressed mood, dyspnea). The 6MWD increased by 2.6 m per month elapsed from acute infection. A 6MWD < 60% was associated with female sex, more intensive respiratory support, four comorbidities (atrial fibrillation, renal failure, chronic pulmonary disease and ischemic heart disease), and two persisting symptoms (nausea/vomiting and palpitations/tachycardia). Exercise performance after COVID-19 is affected by multiple factors, with estimated effect sizes that are clinically relevant. The results also suggest some spontaneous improvement over time.},
}
@article {pmid42380873,
year = {2026},
author = {Wang, XF and Huang, S and Xu, Y and Zou, Y and Zhang, P and Xie, Y and Tsuang, WM},
title = {Multimorbidity patterns and phenotype transitions in patients with clinician-coded long COVID: a multicenter US electronic health record cohort study.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13897-0},
pmid = {42380873},
issn = {1471-2334},
support = {1R01GM152717-01//National Institute of Health/ ; },
abstract = {BACKGROUND: Long COVID is clinically heterogeneous, but longitudinal changes in documented chronic disease burden and transitions in multimorbidity phenotypes after infection are not well characterized in routine care.<br><br>METHODS: We considered 425,614 patients with clinician-coded long COVID (ICD-10-CM U09.9) and a definable COVID-19 index date between October 1, 2021 and September 16, 2024 using deidentified electronic health record data from Epic Cosmos, a multicenter US network. Pre-index and post-index windows were defined as days&#x2009;-&#x2009;365 to -&#x2009;1 and days 91 to 455 relative to infection, respectively; follow-up was available through December 15, 2025. Chronic condition groups derived from ICD-10-CM codes were compared across windows using adjusted generalized estimating equation models. K-modes clustering was used to identify multimorbidity phenotypes, and multinomial regression was used to estimate adjusted transition probabilities.<br><br>RESULTS: Two pre-index phenotypes were identified: low burden (87.9%) and multimorbid (12.1%). Four post-index phenotypes emerged: low burden (63.3%), multimorbid/systemic (21.0%), respiratory-dominant (4.3%), and high-utilization/low-coded multimorbidity (11.3%). Higher baseline multimorbidity was associated with greater probability of transition to the multimorbid/systemic phenotype, whereas respiratory-dominant and high-utilization phenotypes arose from both baseline groups. Increases were concentrated in neurologic/autonomic, respiratory, hypercoagulable, endocrine/metabolic, sleep-related, and symptom-based domains. The high-utilization/low-coded phenotype was younger, predominantly female, and had greater emergency department and outpatient use. Fewer changes reached statistical significance in children than in adults.<br><br>CONCLUSIONS: Among patients with clinician-coded long COVID, chronic disease burden increased after infection and diversified into interpretable post-index phenotypes with distinct utilization profiles, supporting phenotype-informed follow-up and health system planning.},
}
@article {pmid42380995,
year = {2026},
author = {Delano, P and Serra-Suton, V and Benavides, FG and Utzet, M},
title = {Prolonged return to work and hampered work ability: insights from a scoping review on the impact of long COVID on healthcare workers job performance.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-15032-w},
pmid = {42380995},
issn = {1472-6963},
abstract = {BACKGROUND: Healthcare workers (HCWs) may have a higher risk of developing long COVID due to greater exposure to COVID-19, with symptoms extending beyond the acute phase impacting their daily living activities and job performance.<br><br>AIMS: To systematically map the existing literature on the impact of long COVID on HCWs' job performance, focusing on their time to return to work and work ability.<br><br>METHODS: A scoping review following PRISMA-ScR guidance included peer-reviewed studies in English or Spanish (January 2020-December 2024). Four databases were searched. Experimental, epidemiological and qualitative studies were eligible. Two reviewers independently screened records. Methodological quality was appraised using the Mixed-Methods Appraisal tool (MMAT).<br><br>RESULTS: Nineteen studies were included, mainly European and predominantly cross-sectional. Long COVID was most often defined as symptoms lasting&#x2009;&#x2265;&#x2009;3&#x2009;months. Among HCWs with prior infection or whole-staff samples, prevalence ranged from 10% to 74%, with multiple reports above 50%. Thirteen studies evaluated RTW, with 19-63% resumed work within six months, commonly with restrictions, while around one in five remained unable to work in some cohorts. Full-time employment decreased markedly (e.g., 57% pre-infection vs 31% at follow-up). Between 16% and 40% required workplace adjustments such as reduced hours, reassignment, or avoidance of night shifts. Sixteen studies reported diminished work ability compared with pre-infection or unaffected peers. Greater symptom burden, particularly cognitive impairment and fatigue, consistently predicted poorer outcomes. One study estimated a mean of 223&#x2009;days to reach current work-ability levels. Older age, depression, comorbidity, and acute disease severity were recurrent associated factors while evidence for gender and job category was inconsistent.<br><br>CONCLUSIONS: Long COVID delays RTW and reduces work ability in HCWs. Health services should plan long-term occupational follow-up, flexible reintegration pathways, and targeted accommodations while higher-quality longitudinal research refines risk and prognosis.},
}
@article {pmid42381644,
year = {2026},
author = {Caruana, FF and Gelbard, A and Francis, D and Pitman, MJ and Kennedy, EP and Blumin, J and Bock, J and Clary, M and Axelson, Q and Matrka, L and McGarey, P and Daniero, J and Weissbrod, P and Yiu, Y and Gorelik, D and Morrison, RJ and Soliman, S},
title = {Voice Outcomes of Patients Intubated for Critical COVID Illness: A Multicenter Study.},
journal = {OTO open},
volume = {10},
number = {3},
pages = {e70234},
pmid = {42381644},
issn = {2473-974X},
abstract = {OBJECTIVE: Characterize the long-term vocal outcomes of patients who required ICU care for COVID-19 infection.<br><br>STUDY DESIGN: Prospective cohort study.<br><br>SETTING: Multi-institutional North American Airway Collaborative Study.<br><br>METHODS: Patients with a COVID-19 diagnosis requiring ICU admission were identified via ICD-10 codes and recruited after discharge to complete patient-reported outcome measures (PROM) in voice (Voice Handicap Index: VHI-10), communication (Communicative Participation Item Bank: CPIB), and breathing (Clinical COPD Questionnaire: CCQ). Multivariate analysis investigated the association between clinical variables and PROMs.<br><br>RESULTS: 308 patients enrolled; 271 were admitted with COVID to the ICU. 221 were intubated (81.5%); 50 patients admitted to the ICU did not require intubation (18.5%). Mean follow-up was 489 days after discharge (95% CI: 452-526). Mean intubation duration was 17 days (95% CI: 15-19). Median endotracheal tube (ETT) size was 7.5. Intubation was associated with higher VHI-10 score (15 vs 10; P&#x2009;=&#x2009;.01) and lower CPIB score (27 vs 30; P&#x2009;<&#x2009;.01). When controlling for ETT size, multivariate analysis did not show a relationship between intubation duration and VHI-10 or CPIB scores but was associated with worse CCQ score (P&#x2009;=&#x2009;.04).<br><br>CONCLUSION: Survivors of COVID infection requiring ICU admission and intubation have persistent functional impairments in voicing and breathing more than 1 year after their hospitalization. While COVID survivorship and "long COVID" have centered on neuropsychiatric and metabolic outcomes, this study highlights the unappreciated negative impact of endotracheal intubation on voice and communication related to this illness and reinforces the relationship between duration of intubation and subjective dyspnea after surviving critical illness.},
}
@article {pmid42371502,
year = {2026},
author = {Lodemann, P and Tsuprykov, O and Lawaczeck, R},
title = {The Time Course of Serum Iron and Serum Ferritin Concentrations Post-COVID-19 and Influenza Vaccinations.},
journal = {Case reports in infectious diseases},
volume = {2026},
number = {},
pages = {8662747},
pmid = {42371502},
issn = {2090-6625},
abstract = {INTRODUCTION: Temporal responses of serum iron and ferritin in COVID-19 infection and vaccination remain insufficiently characterized. This case report presents their timeline after SARS-CoV-2 and influenza vaccinations and may serve as a model for future studies. The approach can be extended to cohort studies or investigations of other acute-phase reactants. A vaccination protocol with a defined timeline can provide a template for COVID-19 and long COVID studies.<br><br>CASE PRESENTATION: Blood samples were collected from vaccination through 6&#x2009;weeks postvaccination, focusing on iron metabolism. Prevaccination values served as baseline controls. SARS-CoV-2 mRNA vaccination was administered together with routine seasonal influenza vaccination. Previous influenza vaccinations in this patient were not associated with systemic symptoms such as dizziness or fever; in contrast, the present case exhibited clear reactions, suggesting that the observed alterations in serum iron and ferritin are attributable to the SARS-CoV-2 vaccine. The vaccination induced an abrupt decrease in serum iron and a concomitant increase in ferritin. While ferritin returned to baseline within 6&#x2009;weeks, iron levels steadily increased to approximately 1.8-fold above baseline values but remaining within the reference interval.<br><br>DISCUSSION: The observed decrease in serum iron reflects an iron-withholding response, a well-established host defense mechanism during infections that limits pathogen proliferation. The increase in ferritin requires further interpretation. A hypothesis is presented, but further data are needed to support this mechanism. In future cohort studies, the protocol should include individual prevaccination values so that an additional control group is not necessary.<br><br>CONCLUSION: Immune reactions to vaccines can trigger transient changes in serum iron and ferritin that resemble the acute-phase response observed during infections. This case may serve as a template for studying the kinetics of immune responses, where t&#x2009;=&#x2009;0 is defined by the vaccination time and each patient serves as own control when prior data are available.},
}
@article {pmid42371512,
year = {2026},
author = {Cezar da Cruz, D and Haertl, K and Tomlin, GS and Yu, CH and Hernández-Lanas, O and Haigh, J},
title = {Mapping the occupational therapy process in response to COVID-19 and long COVID: A scoping review.},
journal = {The British journal of occupational therapy},
volume = {89},
number = {7},
pages = {435-448},
pmid = {42371512},
issn = {1477-6006},
abstract = {BACKGROUND: COVID-19 and long COVID have had an impact worldwide on people's participation in occupations. Occupational therapists play a role in supporting individuals' recovery and participation in daily life.<br><br>OBJECTIVE: This present study undertook a scoping review of research on COVID-19 and long COVID to map the occupational therapy process with this population, including evaluation, intervention and outcomes.<br><br>METHODOLOGY: Three online databases were searched to identify research papers published between 2020 and 2023 from all countries, published in English, Portuguese, or Spanish. From 455 texts, 25 studies were selected for this review.<br><br>RESULTS: Studies were conducted across varied healthcare settings, mainly inpatient hospitals. Participants ranged from children to older adults, with adults being the most represented group. Standardised assessments included occupational history, activities, body functions, cognition and emotional regulation. Interventions were educational, compensatory, restorative or acquisitional, with outcomes focused on daily living activities, performance skills and client factors.<br><br>CONCLUSION: Our review underscores the need for more comprehensive documentation of occupational therapy effectiveness, particularly in unpredictable circumstances such as COVID.},
}
@article {pmid42376237,
year = {2026},
author = {Matias-Guiu, JA and Arelin, K and Serrano, PJ and Wacker, A and Sória, MG and Burkart, M and Zifko, U},
title = {A randomised, placebo-controlled, triple-blind clinical trial to investigate the efficacy of Ginkgo biloba extract EGb 761[®] in cognitive impairment associated with post COVID-19 syndrome-the EGb COCOS protocol.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1658342},
pmid = {42376237},
issn = {1662-5161},
abstract = {BACKGROUND: Cognitive impairment is frequent in post-COVID-19 syndrome (PCS). The understanding of the pathogenesis is still limited. Key factors such as neuroinflammation, neurovascular dysfunction, and disruption of cellular energy metabolism have been identified. There are no evidence-based treatments targeting the pathologic mechanisms of cognitive impairment associated with PCS available to date. Thus, treatment is directed towards symptom relief. EGb 761[®], a dry extract from the leaves of Ginkgo biloba has anti-neuroinflammatory properties, improves microcirculation and neuronal mitochondrial function. Clinical efficacy in the treatment of cognitive impairment has been demonstrated. It is therefore reasonable to assume that the extract might be beneficial for use in cognitive impairment associated with PCS. Case series of patients with PCS reported significant improvement in cognitive function within 6 months of treatment. The EGb 761[®] Post COVID Cognitive Impairment Study (EGb COCOS) aims to establish whether EGb 761[®] is an effective treatment for cognitive impairment in PCS.<br><br>METHODS: In this prospective, multicentre, randomised, placebo-controlled, triple-blind trial, treatment effects and safety of EGb 761[&#xae;] in patients with cognitive impairment associated with PCS will be investigated. Eligible patients aged &#x2265;18&#x202f;years with a history of probable or confirmed SARS-CoV-2 infection, diagnosis of PCS with cognitive symptoms that have been present for at least 2&#x202f;months, objective cognitive impairment, and mild-to-moderate anxiety or depressive symptoms will be enrolled. Participants (n&#x202f;=&#x202f;400 planned) will be randomised to oral, 12-week treatment with EGb 761[&#xae;] (240&#x202f;mg) or matching placebo once daily. The effect of EGb 761[&#xae;] will be assessed on cognitive, neuropsychiatric, neurosensory, and functional outcomes. The analysis will be exploratory in nature, since generally accepted and validated primary endpoints have not been established. For safety, the incidence of adverse events (AEs) and serious AEs will be recorded.<br><br>DISCUSSION: The results of this trial will show for the first time whether EGb 761[&#xae;] is an effective treatment for cognitive impairment in PCS.<br><br>CLINICAL TRIAL REGISTRATION: https://euclinicaltrials.eu/ctis-public/view/2024-517199-39-00?lang=en, Identifier CTIS2024-517199-39-00.},
}
@article {pmid42376321,
year = {2026},
author = {Telles, AFC and Menezes Junior, BS and Dos Santos, CA and Sena, LOC and Alves, MRM and Moraes, MLAM and Cipolotti, R},
title = {Genetic association between LONG COVID and TMPRSS2 polymorphisms (rs12329760 and rs2070788) in Brazilian healthcare professionals.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1731318},
pmid = {42376321},
issn = {2235-2988},
mesh = {Humans ; *Polymorphism, Single Nucleotide ; Brazil/epidemiology ; Female ; *Serine Endopeptidases/genetics ; Adult ; *COVID-19/genetics/epidemiology ; Post-Acute COVID-19 Syndrome ; *Health Personnel ; Male ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Middle Aged ; Young Adult ; Genotype ; Adolescent ; SARS-CoV-2 ; },
abstract = {Long COVID syndrome has a multifactorial cause that is not fully understood and may be influenced by both external and intrinsic factors. In this context, a Genome-Wide Association Study (GWAS) was proposed to evaluate the association between Single Nucleotide Polymorphisms (SNPs) in TMPRSS2 (rs12329760 and rs2070788) and the occurrence of Long COVID in 363 Brazilian healthcare professionals, recruited using a non-probabilistic method. The study employed a self-report questionnaire to collect sociodemographic and clinical data from both the acute and chronic phases and also collected oral mucosa cells for genotypic analysis by qPCR using Taqman probes. The categorized information was analyzed using the PSPP software using Pearson's chi-square test in three genetic statistical models: additive, dominant, and recessive. Assessing long COVID in general, only clinical variables such as increased susceptibility, presence of symptoms, and severity influenced the occurrence of the syndrome. When specifying the main reported symptom, brain fog, females and young adults (18 to 29 years old) are the most vulnerable, and rs2070788 in the recessive model proved to be relevant. This association is more evident when evaluating only the symptomatic group in the post-COVID period, as the additive model also influences the groups. rs12329760 showed no relevant influence on the groups. Therefore, this study provides unprecedented evidence of the association between brain fog and rs2070788, requiring case-control studies to better clarify how this association occurs.},
}
@article {pmid42363551,
year = {2026},
author = {Wen, J and Chen, Y and Zhang, J and Tan, Z and Xia, Z and Yang, S and Liu, H},
title = {Genetic evidence that advanced COVID-19 accelerates longitudinal brain atrophy: A Mendelian randomization study.},
journal = {Medicine},
volume = {105},
number = {26},
pages = {e49310},
pmid = {42363551},
issn = {1536-5964},
mesh = {Humans ; *COVID-19/genetics/complications ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Brain/pathology/diagnostic imaging ; Atrophy/genetics ; Magnetic Resonance Imaging ; SARS-CoV-2 ; Aging/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Longitudinal Studies ; },
abstract = {Coronavirus disease 2019 (COVID-19) was reported to persist long-term in the brain and leave several long-term neurologic sequelae. However, the causal relationship between COVID-19 and brain aging is still unknown. The genome-wide association study (GWAS) data on COVID-19 phenotypes (susceptibility, hospitalization, and severity), involving a total of 5,779,391 participants, were collected from the COVID-19 Host Genetics Initiative. In addition, GWAS data on longitudinal changes in 15 brain structures, assessed via magnetic resonance imaging across the lifespan, were sourced from the ENIGMA Consortium and involved 15,640 participants. Two-sample Mendelian randomization was conducted to infer the causal relationship between COVID-19 and longitudinal brain changes. Multi-trait GWAS meta-analysis, colocalization, and fine-mapping analyses were performed to identify shared genetic etiologies. H3K27me3 ChIP-seq was used to evaluate the regulatory effect of colocalized loci. Two-step Mendelian randomization was applied to explore potential mediating mechanisms across multi-omics layers, including proteomics, metabolomics, and immunomics. Our results showed that COVID-19 hospitalization (β = -262.405, P = .041) and severity (β = -177.676, P = .049) were genetically associated with atrophied volume of total brain during longitudinal change. This suggests that individuals with advanced COVID-19 may be more susceptible to accelerated global brain aging. Caudate was genetically affected by all COVID-19 phenotypes. Seven variants were shared between advanced COVID-19 and global brain aging. rs117169628 was colocalized between advanced COVID-19 and global brain aging, and exerted an inhibitory effect on CDH15 expression, further strengthening the causality. Six metabolites, 1 protein, and 1 immune trait were identified as potential mediators. Our study indicates that advanced COVID-19 might be genetically associated with accelerated brain aging. Brain health should be paid more attention in long COVID-19.},
}
@article {pmid42364466,
year = {2026},
author = {Bandeira Barboza, AP and Monteiro, RL and Muschi, AL and Dos Santos Silva, AR and Silva, DAD and Silveira, RC and Alencar Silva, CS and de Castro, GS and Santana, JV and Soares Silva, RDS and Cerri, GG and Rodrigues Pereira, AJ and Beco, MA and Romitelli, G and Veneziani, JR and Santos Silva, EMD and Barboza, ADS and Mattar, LL and Sabino, EC and Ribeiro, RS and Costa, SF},
title = {Artificial intelligence-enhanced nurse navigation for monitoring and care of long COVID.},
journal = {International journal of medical informatics},
volume = {219},
number = {},
pages = {106557},
doi = {10.1016/j.ijmedinf.2026.106557},
pmid = {42364466},
issn = {1872-8243},
abstract = {INTRODUCTION: Long COVID is a multisystem condition with challenging diagnosis. Nurse-navigation, a patient-centered intervention, can enhance education and care access. Analyzing patient-nurse text message exchanges using natural language processing (NLP) enables automated extraction of clinical information, potentially supporting early identification of long COVID. We aimed to evaluate a digital nurse navigation platform integrating a predictive model for long COVID identification as a triage-assisting tool and to assess user acceptance.<br><br>METHODS: This observational study included patients and healthcare professionals diagnosed with COVID-19 from January to July 2024. Participants received nurse-navigation support for 16&#xa0;weeks with monthly interactions via a WhatsApp-integrated platform. Structured sociodemographic and clinical data were combined with text-message insights using NLP techniques such as term frequency-inverse document frequency (TF-IDF), and analyzed using language models (Gemini 1.5 Pro, BERTimbau) and probabilistic linkage. The dataset was split into 70% training and 30% testing, and eight machine learning models were evaluated. Performance metrics included accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC). User satisfaction was assessed with the Net Promoter Score (NPS).<br><br>RESULTS: Among 177 participants, 141 (78%) were female, with an overall mean age of 51&#xa0;years. A total of 7,016 messages were processed. Long COVID was identified in 60 participants (33%), most frequently reporting memory loss, dyspnea, cognitive fatigue, and hair loss. Participants received structured education, and 20 were referred for further evaluation. The XGBoost-minor model achieved the highest classification performance with an accuracy of 72%, sensitivity of 38%, specificity of 88%, PPV of 63%, NPV of 74%, and AUROC 0.59. Predictive factors included age, COVID-19 episodes, vaccination, comorbidities, and respiratory symptoms. The NPS was 92, indicating strong endorsement.<br><br>CONCLUSION: An AI-enhanced triage process within nurse navigation represents a promising and scalable strategy to support the identification and monitoring of patients at risk for long COVID.},
}
@article {pmid42367370,
year = {2026},
author = {Tan, HL and Rosser, E and Hernandez, AL and Fei, YC and Azola, A and Parker, A and Galiatsatos, P and Smith, CL and Shea, P and Cox, AL and Klein, SL and Morgan, R},
title = {"That's not my silo": Navigating fragmented long COVID care in the mid-Atlantic United States.},
journal = {SSM. Qualitative research in health},
volume = {9},
number = {},
pages = {},
pmid = {42367370},
issn = {2667-3215},
abstract = {BACKGROUND: Long COVID is a chronic illness affecting multiple organ systems, which can be at odds with a highly specialized and siloed U.S. healthcare system. Patients frequently see multiple specialists for diverse symptoms, creating substantial coordination challenges.<br><br>METHODS: We conducted a qualitative study using semi-structured interviews with 69 U.S. Mid-Atlantic adults diagnosed with or suspected of having Long COVID, recruited through a Long COVID clinic, MyChart patient-portal outreach, and snowball sampling. Interviews were conducted via Zoom, phone, or in person, audio-recorded, transcribed, and analyzed using the Framework Approach.<br><br>RESULTS: Participants described significant difficulty navigating a fragmented healthcare system characterized by siloed care, communication breakdowns, long wait times, and unclear provider responsibilities, as well as difficulties obtaining a diagnosis. When coordination failed, patients were often forced to organize and direct their own healthcare, a task that was cognitively and physically taxing, particularly for those experiencing brain fog and fatigue, and, for some, ultimately led to delaying or forgoing care.<br><br>CONCLUSION: Strengthening care coordination for Long COVID could reduce patient burden and improve access to care. Needed strategies include standardized diagnostic definitions, enhanced primary care roles, interoperable referral pathways, and institutional case conferencing to clarify provider responsibilities. Patient navigators, expanded telehealth options, and community-based support, especially culturally tailored services for disproportionately affected groups, may further reduce fragmentation, scheduling strain, and inequities. Addressing these systemic barriers is essential to creating a more efficient, patient-centered care experience in which patients are no longer responsible for coordinating their own complex care.},
}
@article {pmid42369154,
year = {2026},
author = {Salomão, R and Pasquarelli-do-Nascimento, G and Ananias, M and Assis, V and Ferreira, LGJ and da Silva Almeida, I and Silva, L and Tostes, K and Sorroche, BP and Arantes, LMRB and Magalhães, KG and García, LT and Rocha Costa, R and Quagliotti Durigan, JL and Marqueti, RC},
title = {Longitudinal trajectories of hematological indices and serum metalloproteinases-2 and 9 over 1 year after moderate and severe COVID-19.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1824883},
pmid = {42369154},
issn = {2296-858X},
abstract = {INTRODUCTION: The long-term clinical burden of Coronavirus disease (COVID-19) remains substantial, yet one-year cohort evidence linking blood-based biomarkers to persistent sequelae is limited.<br><br>METHODS: We conducted a longitudinal study in adults aged 18-80&#x202f;years who were classified as moderate or severe COVID-19 or non-COVID-19 controls. Blood was collected at four time points through 360&#x202f;days after infection or hospital discharge. Cytokines were quantified by flow cytometry. MMP-2 and MMP-9 levels and activity were assessed by gelatin zymography. Hematological parameters were measured in an accredited clinical laboratory. Longitudinal effects were evaluated using generalized estimating equations.<br><br>RESULTS: Compared with moderate cases and controls, participants who experienced severe acute disease showed persistent immune dysregulation and systemic inflammation at approximately 1 year, with higher concentrations of inflammatory mediators and cytokines and sustained elevations in MMP-2 and MMP-9. Complete blood count-derived indices were also altered over time in severe cases, including the aggregate index of systemic inflammation, the C-reactive protein to lymphocyte ratio, the neutrophil to platelet ratio, and the systemic inflammation response index, together with red cell distribution width, while renal function tests, hepatic enzymes, and muscle injury markers were largely stable across groups.<br><br>DISCUSSION: These findings delineate a persistent inflammatory and matrix-remodeling signature up to 1 year after severe COVID-19, based on longitudinal biomarker profiles rather than symptom-defined long COVID-19 outcomes. This biomarker panel may help to inform future studies of post-acute risk stratification and targeted interventions, but prospective prognostic validation and clinical endpoint data are still required.<br><br>CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04961255?term=NCT04961255&amp;rank=1, NCT04961255.},
}
@article {pmid42370768,
year = {2026},
author = {Applewhite, TL},
title = {Idiopathic anaphylaxis and histamine dysregulation: Revisiting pathophysiologic assumptions.},
journal = {The Nurse practitioner},
volume = {51},
number = {7},
pages = {42-45},
doi = {10.1097/01.NPR.0000000000000455},
pmid = {42370768},
issn = {1538-8662},
mesh = {Humans ; *Anaphylaxis/physiopathology/nursing/immunology ; *Histamine/immunology ; Immunoglobulin E/immunology ; },
abstract = {Idiopathic anaphylaxis (IA) is a diagnosis of exclusion, and the etiology remains elusive. Research on immunoglobulin E (IgE)-mediated anaphylaxis has identified histamine as the immune system mediator, but dietary histamine's potential role in IA is often overlooked. For some individuals, excessive histamine may cause IA and mimic signs and symptoms of IgE-mediated anaphylaxis.1 This review provides an overview of IA and the potential role of histamine in symptom manifestation. It aims to enhance awareness and provide nurse practitioners with insights into the complexities of managing IA, emphasizing the importance of considering dietary factors in patient care and treatment strategies.},
}
@article {pmid42371051,
year = {2026},
author = {Müller, B and Balz, U and Bartels, K and Eggers, F and Löbermann, M and Nostitz, L and Schmidt, J and Schwarz, C and Wossidlo, C and Reisinger, EC and Kropp, P},
title = {Post-COVID: a specific neuropsychological profile in performance deficits.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42371051},
issn = {1435-1463},
abstract = {BACKGROUND: SARS-CoV-2 is frequently associated with cognitive impairment. When symptoms persist for more than four weeks after acute infection, a Long-COVID condition is diagnosed. When persisting more than 12 weeks, Post-COVID ist diagnosed. Cognitive complaints commonly include impairments in attention, memory, and executive functions. However, precise data on the specific pattern and extent of these deficits remain limited.<br><br>METHODS: Results: Conclusions: The findings indicate that attentional impairments are more prevalent than memory deficits in this Post-COVID cohort. Furthermore, distinct cognitive profiles can be identified using cluster analysis, ranging from globally impaired to cognitively preserved subgroups. These results may be relevant for clinical characterization and rehabilitation planning in Post-COVID conditions.<br><br>METHODS: We examined 88 patients (mean age 50.9 years, 80.7% female) diagnosed with COVID symptoms according to the WHO-criteria. Neuropsychological assessment was performed using a standardized test battery covering attentional performance, working memory, and executive functions. A cluster analysis was conducted to identify subgroups based on cognitive performance profiles.<br><br>RESULTS: Overall, 55.7% of patients showed below-average attentional performance, whereas memory deficits were less frequent (33.0%). Impairments in executive functions were similarly distributed across the sample. Cluster analysis yielded a three-cluster solution. Cluster 1 (34.1%) was characterized by pronounced impairments across all cognitive domains. Cluster 2 (20.0%) showed generally below-average cognitive performance; however, verbal fluency was preserved at or above average in all participants. In Cluster 3 (17.6%) more than 50% of patients in performed within average to above-average ranges across all cognitive domains.<br><br>CONCLUSIONS: The findings indicate that attentional impairments are more prevalent than memory deficits in this Post-COVID cohort. Furthermore, distinct cognitive profiles can be identified using cluster analysis, ranging from globally impaired to cognitively preserved subgroups. These results may be relevant for clinical characterization and rehabilitation planning in Post-COVID conditions.},
}
@article {pmid42362970,
year = {2026},
author = {Said, N and Jones, I and Anderson-Baucum, EK and Evans-Molina, C},
title = {SARS-CoV-2 and diabetes: a post-pandemic reappraisal.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
pmid = {42362970},
issn = {1432-0428},
support = {I01BX001733//U.S. Department of Veterans Affairs/ ; P30DK097512/DK/NIDDK NIH HHS/United States ; R01DK093954/DK/NIDDK NIH HHS/United States ; R01DK127308/DK/NIDDK NIH HHS/United States ; },
abstract = {The COVID-19 pandemic was a dynamic and often confusing period for clinical and biomedical research. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread globally, knowledge accumulated rapidly through publications that were frequently based on preliminary or sometimes conflicting evidence, yet these papers played a critical role in shaping evolving medical, research and societal responses. Early in the pandemic, diabetes emerged as one of the strongest predictors of severe COVID-19 outcomes and mortality, placing it at the centre of early risk-stratification and therapeutic frameworks and prompting urgent efforts to understand the biological basis of these associations. As the pandemic progressed, reports of new-onset diabetes following COVID-19 infection raised the possibility of a bidirectional relationship between SARS-CoV-2 infection and diabetes. In this review, we provide a post-pandemic reappraisal of the clinical and experimental literature examining the intersection of COVID-19 and diabetes. We summarise proposed pathophysiological mechanisms, including the effects of SARS-CoV-2 infection in the pancreas and on peripheral insulin-sensitive tissues. We review key meta-analyses assessing the association between COVID-19 and incident type 1 and type 2 diabetes and highlight strengths and weaknesses of the epidemiologic studies underpinning these findings. We highlight the highest-quality evidence from prospective cohorts, as well as relevant clinical trials and registry-based studies that emerged from this collective experience. We discuss emerging relationships between long COVID and diabetes and the effect of vaccination on diabetes risk following SARS-CoV-2 infection. Finally, we identify critical knowledge gaps and outline priorities for ongoing and future studies needed to resolve remaining uncertainties.},
}
@article {pmid42363216,
year = {2026},
author = {Zhang, X and Rajaraman, PK and Comellas, AP and Hoffman, EA and Yang, T and Guo, J and Lin, CL},
title = {Bronchovascular texture pattern on quantitative CT reveals airway and vascular remodeling in post-COVID-19 Lungs.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03784-2},
pmid = {42363216},
issn = {1465-993X},
support = {NIH R01-HL168116/NH/NIH HHS/United States ; ED P116S210005//Department of Education, United States/ ; },
abstract = {BACKGROUND: The long-term consequences of COVID-19 remain poorly understood.<br><br>PURPOSE: To assess CT image-based biomarkers and clinical symptoms in COVID-19 survivors approximately 3-4 years after infection.<br><br>MATERIALS AND METHODS: Eighty post-COVID-19 participants (81% infected with the pre-Alpha strain) underwent pulmonary function tests (PFTs) and inspiratory/expiratory CT at approximately 5 months (Visit 1, V1) and 3-4 years (Visit 2, V2) after infection. At V2, participants completed the St. George's Respiratory Questionnaire (SGRQ), Leicester Cough Questionnaire (LCQ), Fatigue Severity Scale (FSS), modified Medical Research Council Dyspnea Scale (mMRC), and a study-specific symptom and medical history questionnaire. Seventy-eight healthy individuals served as controls. Image-based biomarkers included airway diameter, airway wall thickness, functional small airway disease percentage (fSAD%), ground-glass opacity percentage (GGO%), and bronchovascular percentage (Bronchovascular%).<br><br>RESULTS: Post-COVID-19 participants exhibited normal predicted PFT values, but consistently lower DLCO compared with healthy controls at both visits. At V2, they also reported significantly worse SGRQ scores than the general population, indicating reduced quality of life. Although the elevated fSAD% and GGO% observed at V1 largely resolved by V2, several biomarkers of airway and vascular remodeling persisted, including increased Bronchovascular%, airway narrowing and wall thickening, and a compositional shift from large to small airways and a shift from small to large vessels. Persistent symptoms-such as fatigue, brain fog, cough, and hypertension-were associated with these structural abnormalities.<br><br>CONCLUSION: Airway and vascular structural abnormalities persisted in COVID-19 survivors 3-4 years after infection and were associated with ongoing symptoms and reduced quality of life.},
}
@article {pmid42350987,
year = {2026},
author = {Yang, S and Wen, X and Lin, Y and Zhang, R and Luo, D},
title = {Expression levels of SARS-CoV-2 IgM, IgG, and neutralizing antibodies in a Chinese cohort and detection of peptide-specific antibodies in COVID-19 patients.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13532-y},
pmid = {42350987},
issn = {1471-2334},
support = {2023YFA0915602//National Key R&amp;D Program of China/ ; JCYJ20240813114502004//Shenzhen Natural Science Foundation Project/ ; 82273236//General Projects of the National Natural Science Foundation of China/ ; NSZD2023020//Newly introduced discipline leader fund project in Nanshan District of Shenzhen City/ ; },
abstract = {BACKGROUND: Long COVID is a complex multisystem disorder affecting approximately 65 million individuals worldwide, with autoimmune mechanisms implicated in its pathogenesis. This study aimed to elucidate the role of SARS-CoV-2-induced autoantibodies and immune dysregulation in the development of Long COVID, focusing specifically on autoimmunity and aberrant immune activation. The investigation sought to explore the underlying mechanisms through serological and peptide-based analyses.<br><br>METHODS: Serum samples from 315 healthcare workers, serving as a control cohort, were analyzed for the presence of SARS-CoV-2 IgM, IgG, and Neutralizing Antibodies (NAbs), with stratification based on age, gender, vaccination timing, and symptom clusters. Bioinformatic approaches were employed to identify SARS-CoV-2 epitopes with homology to human proteins, screening for epitopes of the SARS-CoV-2 Spike (S) and Nucleocapsid (N) proteins and their human homologous peptides through analyses of hydrophilicity, antigenicity, and homology prediction. An ELISA-based method was utilized to detect antibody responses to these peptides in both COVID-19 infected groups (categorized as mild, moderate, or severe) and an uninfected group.<br><br>RESULTS: The primary findings indicated a high seropositivity rate for IgG (97%) and Neutralizing Antibodies (94%) among the control group, with notable age-related trends: IgM levels increased with age, whereas IgG and Neutralizing Antibodies showed a decline. Female participants demonstrated higher IgG levels compared to their male counterparts. Antibody levels did not exhibit significant differences across acute or persistent symptom clusters (&#x2265;&#x2009;6 months post-infection). However, neurological symptoms, whether acute or chronic, were associated with elevated IgG and Neutralizing Antibody titers, suggesting that neurotropic infections may elicit a more robust humoral immune response. Bioinformatic analyses identified 29 potential epitopes within the S protein and 10 within the N protein, with 91 and 24 human homologous peptides, respectively. The detection of peptide-specific antibodies in the serum of the COVID-19 infected group revealed that antibodies against eight peptides displayed a greater than 2.5-fold difference between the COVID-19-infected and uninfected groups.<br><br>CONCLUSION: These findings underscore age- and gender-related variations in antibody responses, identify immunodominant peptides with potential implications for COVID-19 symptoms, and suggest that cross-reactive antibodies targeting viral-human homologous peptides (e.g., S68-CHL1) may play a role in autoimmune mechanisms associated with COVID-19.<br><br>TRIAL REGISTRATION: Clinical trial number: Not applicable.},
}
@article {pmid42351174,
year = {2026},
author = {Chambers, PW},
title = {Magnesium and gender in long COVID.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {42351174},
issn = {1479-5876},
}
@article {pmid42351227,
year = {2026},
author = {Kumar, N and Khandavalli, N and Avedissian, SN and Chand, HS and Acharya, A and Byrareddy, SN},
title = {Translational insights into Long-COVID: evaluation of preclinical animal models along the lung-brain-immune axis with focus on Golden Syrian Hamsters.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03928-7},
pmid = {42351227},
issn = {1742-2094},
support = {DA052845, DA059874, DA061678/NH/NIH HHS/United States ; },
abstract = {Long-COVID, also referred to as post-acute sequelae of COVID-19 (PASC), is a heterogeneous disorder encompassing more than 200 reported symptoms that commonly affect the respiratory and nervous systems. Emerging clinical evidence indicates that unresolved lung inflammation, vascular injury, and immune dysregulation drive sustained neuroinflammation and impaired neurocognitive function in Long-COVID patients. Given the ethical and logistical constraints of human studies, biologically relevant animal models are essential for understanding the mechanisms and for evaluating therapeutic strategies against Long-COVID. In this review, we synthesize current evidence from preclinical animal models of Long-COVID, with a particular emphasis on the Golden Syrian Hamsters. Golden Syrian Hamsters are naturally susceptible to SARS-CoV-2 infection without the need for genetic modification and recapitulate key features of human disease, including robust viral replication, pulmonary pathology, and inflammatory response during acute infection. Importantly, accumulating evidence demonstrates that Golden Syrian Hamsters develop persistent post-acute abnormalities along the lung-brain-immune axis, including impaired alveolar repair, fibrotic lung remodeling, neuroinflammation, viral or antigen persistence, and behavioral alterations that parallel core features of Long-COVID. We compare the strengths and limitations of Golden Syrian Hamsters with other commonly used pre-clinical animal models including mice, and non-human primates, highlighting differences in translational relevance, feasibility, and ability to model chronic lung-brain-immune axis dysfunction. While there are limitations, particularly regarding limited availability of immunological reagents and validated cognitive and behavioral assays, the Golden Syrian Hamsters offers a balanced and accessible platform for mechanistic studies of PASC. Overall, this review positions Golden Syrian Hamster as a robust translational model for investigating lung-brain-immune axis pathology in Long-COVID and for advancing the development of targeted therapeutic interventions.},
}
@article {pmid42351611,
year = {2026},
author = {Donchev, D and Nikolova, R and Vaseva, K and Taskov, H and Murdjeva, M and Maes, M and Ivanov, IN},
title = {Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome.},
journal = {Biomedicines},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/biomedicines14061183},
pmid = {42351611},
issn = {2227-9059},
support = {project &#x2116; BG-RRP-2.004-0007-&#x421;03//European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria/ ; },
abstract = {Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited. Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores. Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H2 carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals. Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns.},
}
@article {pmid42352829,
year = {2026},
author = {Malykh, S and Demareva, V and Malykh, A and Ismatullina, VI and Adamovich, T and Kolyasnikov, P and Tikhomirova, T},
title = {Post-COVID-19 Consequences and Psychological Well-Being in Students: The Mediating Role of Trait Anxiety.},
journal = {Behavioral sciences (Basel, Switzerland)},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/bs16060996},
pmid = {42352829},
issn = {2076-328X},
support = {24-18-01102//Russian Science Foundation/ ; },
abstract = {The long-term psychological consequences of COVID-19 remain insufficiently understood in student populations. This study examined the association between post-COVID-19 consequences and psychological functioning in university students, focusing on the mediating role of trait anxiety. A total of 7482 students aged 17 to 23 years completed an online survey assessing COVID-19 history, post-COVID-19 consequences, psychological well-being (WHO-5), subjective happiness (SHS), life satisfaction (SWLS), and trait anxiety (STAI). Participants were classified into three groups: no history of COVID-19, COVID-19 without post-COVID-19 consequences, and COVID-19 with post-COVID-19 consequences. Group differences were analyzed using ANOVA with Tukey post hoc tests, followed by regression and mediation analyses controlling for age and sex. Students reporting post-COVID-19 consequences showed higher trait anxiety and lower psychological well-being, subjective happiness, and life satisfaction than both comparison groups. Regression analyses indicated that poorer psychological functioning was associated specifically with post-COVID-19 consequences rather than COVID-19 history per se. Mediation analyses among previously infected students showed that trait anxiety statistically mediated these associations, accounting for 61% of the effect on psychological well-being, 84% on subjective happiness, and 68% on life satisfaction. These findings highlight trait anxiety as an important psychological factor statistically accounting for the association between post-COVID-19 consequences and reduced well-being.},
}
@article {pmid42354218,
year = {2026},
author = {Habuddha, V and Piya-Amornphan, N},
title = {Understanding the Impact of Long COVID on the Lives of Thai University Students.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {6},
pages = {},
doi = {10.3390/ijerph23060687},
pmid = {42354218},
issn = {1660-4601},
mesh = {Humans ; Thailand/epidemiology ; Female ; *Quality of Life ; *COVID-19/psychology/epidemiology ; *Students/psychology ; Male ; Universities ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Young Adult ; Adult ; *Mental Health ; SARS-CoV-2 ; Surveys and Questionnaires ; Sleep Quality ; Pandemics ; Fatigue/epidemiology ; Sleep Wake Disorders/epidemiology ; },
abstract = {COVID-19 has had profound global impacts, and Long COVID may continue to affect quality of life and well-being in some individuals. Young adults may be particularly vulnerable to these impacts due to ongoing physiological, behavioral, and psychological development. This study aimed to examine the associations between Long COVID, mental health-related outcomes, and quality of life among university students. A total of 365 Thai undergraduate students participated in this cross-sectional study screening for Long COVID. Long COVID symptoms, mental health, sleep quality, and quality of life were assessed using validated Thai versions of the Long COVID Screening Questionnaire, DASS-21, PSQI, and EQ-5D-5L. Regression and group comparison analyses were conducted between participants with Long COVID and those without Long COVID. Fatigue and cough were the most reported symptoms, while sleep disturbances were also prevalent. Long COVID was associated with significantly lower quality of life scores (p = 0.035). However, no significant differences were observed in DASS-21 or PSQI scores between groups. Vaccination doses and prior COVID-19 infections differed significantly between groups (p < 0.001 and p = 0.017). These findings highlight the multisystem impacts of Long COVID and emphasize the importance of identification and supportive interventions to enhance student health and well-being.},
}
@article {pmid42354489,
year = {2026},
author = {Chen, YH and Lin, CH and Liu, JH and Lin, HA and Hsieh, YS},
title = {Association Between Prior NRICM101 Use and Response to Incentive Spirometer Training in Patients with Long COVID.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/healthcare14121630},
pmid = {42354489},
issn = {2227-9032},
support = {TSGH-SS_D_113004 and TSGH-SS_D_115024//Tri-Service General Hospital Beitou Branch/ ; },
abstract = {Background: Inspiratory training using an incentive spirometer (IS) improves respiratory symptoms and functional status in Long COVID. In Taiwan, NRICM101 is commonly used during the acute phase; however, its impact on rehabilitation outcomes remains unclear. Objective: This study evaluated the effects of IS-based respiratory training and the potential influence of prior NRICM101 use. Methods: Participants were grouped by time since recovery, and pre-post changes after six weeks of IS training were compared between those with and without self-reported prior NRICM101 use. Primary outcomes were dyspnea and functional status; secondary outcomes included six-minute walk distance and arterial oxygen content. Results: IS training significantly improved dyspnea (p < 0.0001), functional status (p < 0.0001), and exercise endurance (NRICM101 group: p = 0.002; no NRICM101 group: p < 0.0001). Stratified analysis showed that when initiated within three months of recovery, participants without prior NRICM101 use had greater improvements in dyspnea (p < 0.0001), functional status (p = 0.001), and exercise endurance (p < 0.0001). Conclusions: Prior NRICM101 use may be associated with different rehabilitation patterns, likely reflecting differences in recovery trajectory or patient behavior rather than purely pharmacological effects.},
}
@article {pmid42354584,
year = {2026},
author = {Shahzad, M and Siddiqui, S and Lau, C and Lamptey, DL and Ezeugwu, VE and Maina, G and Maddison, CJ and Flowers, K and Shah, AR and Welithotage, T and Nowrouzi-Kia, B},
title = {Symptom, Functional, and Work Participation Profiles Among Racialized Canadians with Pre-Existing Mental Health Challenges and Long COVID: A Cross-Sectional Study.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/healthcare14121726},
pmid = {42354584},
issn = {2227-9032},
support = {Seed funding//Long covid web/ ; },
abstract = {BACKGROUND/OBJECTIVES: Long COVID is associated with persistent, multi-system symptoms, yet little is known about how it affects individuals with intersecting vulnerabilities, such as a racialized identity and pre-existing mental health conditions. This study aimed to descriptively characterize the symptom burden, functional outcomes and mental health in this population.<br><br>METHODS: A cross-sectional, exploratory study was conducted among 51 adults in Canada who self-identified as racialized and as having a pre-existing mental health condition and reported long COVID symptoms. Participants completed an online survey, including validated measures of symptoms, fatigue, post-exertional malaise, cognitive function, mental health and disability. Descriptive statistics were used to summarize outcomes.<br><br>RESULTS: Participants reported a slight to moderate overall symptom burden, with the highest scores in respiratory and psychological domains. Functional impairment was moderate across work, social and daily activities (Work and Social Adjustment Scale mean = 17.35; World Health Organization Disability Assessment Schedule 2.0 mean = 16.61; Post COVID-19 Functional Status Scale mean = 2.20). Fatigue and post-exertional malaise were notable (Modified Fatigue Impact Scale mean = 43.39; DePaul Symptom Questionnaire-Post-Exertional Malaise mean = 22.47), and cognitive difficulties were commonly reported (Perceived Deficits Questionnaire mean = 33.43). Anxiety and depression scores were in the mild to moderate range respectively (General Anxiety Disorder-7 mean = 9.27; Patient Health Questionnaire-9 mean = 11.43).<br><br>CONCLUSIONS: Clinically relevant fatigue, post-exertional malaise, and depression were found, alongside moderate functional limitations across life domains. The findings support the conceptualization of long COVID as a syndemic condition and underscore the need for equity-informed research, rehabilitation and public health strategies.},
}
@article {pmid42354937,
year = {2026},
author = {Churilov, LP and Starshinova, A and Kudryavtsev, I and Rubinstein, A and Koroteeva, O and Kulpina, A and Ryabkova, VA and Sabirova, A and Sobolevskaia, P and Fedotkina, T and Kudlay, D},
title = {Immunological Mechanisms and Machine Learning Applications in Post-COVID-19 Syndrome: A Narrative Review.},
journal = {Microorganisms},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/microorganisms14061313},
pmid = {42354937},
issn = {2076-2607},
support = {075-15-2025-013//Ministry of Science and Higher Education/ ; },
abstract = {UNLABELLED: Post-COVID-19 syndrome (PCS), also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), represents a heterogeneous set of persistent clinical manifestations developing after acute infection. These conditions are associated with immune dysregulation, autonomic imbalance, impaired thymic function, and possible viral persistence.<br><br>OBJECTIVE: This study aims to systematically synthesise current evidence on the immunopathogenesis of PCS and to critically evaluate the application of artificial intelligence (AI) and machine learning (ML) approaches for its prediction and clinical stratification.<br><br>METHODS: A PRISMA 2020-informed systematic review was conducted using PubMed/MEDLINE, Scopus, Web of Science, elibrary.ru and Embase databases (January 2020-December 2025). Studies addressing immunopathological mechanisms and AI/ML applications in PCS were selected based on predefined eligibility criteria. Risk of bias in prediction studies was assessed using the PROBAST tool. Due to heterogeneity, a structured qualitative synthesis was performed. Current evidence indicates that PCS may result from sustained systemic inflammation, cytokine dysregulation, autoimmunity, and delayed restoration of T-cell homeostasis, including reduced thymic output of na&#xef;ve T lymphocytes. Persistent thymic dysfunction may contribute to prolonged immune imbalance, increased susceptibility to secondary infections, and reactivation of latent viruses. AI/ML approaches-including gradient boosting, ensemble learning, deep neural networks, and natural language processing-have demonstrated promising performance across multimodal datasets. However, significant limitations were identified, including small sample sizes, overfitting, lack of external validation, and heterogeneity in outcome definitions.<br><br>CONCLUSIONS: The integration of immunopathological insights with data-driven modelling highlights the potential of combined approaches for improving PCS risk stratification. However, current AI models remain insufficiently validated for clinical implementation. Future research should prioritise methodological standardisation, external validation, and incorporation of mechanistically informed biomarkers.},
}
@article {pmid42355811,
year = {2026},
author = {Khawandi, J and Choaib, A and Azzam, M and Oudit, GY and Patel, K and Nazzal, J and Khader, AA and Kawtharany, H and Al Zabibi, MA and Ahmad, J and Kivan, H and Al Hussein, S and Rehman, AU and Piché, A and Vasquez Camargo, A and McNaughton, C and Lam, GY and Kamrul, R and Afzal, S and Schunemann, HJ and Wiercioch, W and Nieuwlaat, R and Brignardello-Petersen, R and Falcone, EL and Mustafa, RA},
title = {Echocardiogram Testing in Patients with Post-COVID-19 Condition: A Systematic Review and Meta-Analysis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/jcm15124643},
pmid = {42355811},
issn = {2077-0383},
support = {2223-HQ-000415//Public Health Agency of Canada/ ; },
abstract = {Background: Post-COVID-19 condition (PCC) is a complication following acute COVID-19 infection, which may lead to long-term cardiac abnormalities. This review aimed to assess the prevalence of structural/functional deviations in echocardiography in individuals with PCC compared to patients without PCC. Methods: We searched three databases. Two reviewers independently screened articles using LASER Al and extracted relevant data using a piloted Excel sheet. We performed meta-analysis using OpenMeta and RevManWeb and a subgroup analysis based on patients' settings during acute COVID-19. We assessed the risk of bias using the Hoy et al. tool and the certainty using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 16 studies that reported on differences in echocardiographic findings in patients with or without PCC. Individuals with PCC were more likely to have structural/functional deviations in echocardiographic readings of unclear clinical significance, particularly those who were hospitalized during acute COVID-19. The overall certainty of the evidence was very low due to the high risk of bias, indirectness, and imprecision. Conclusions: This review provides insight into the use of echocardiograms and the frequency of test deviations in individuals with PCC. Despite existing evidence, there is a need for future studies to assess the diagnostic test accuracy of echocardiograms in PCC.},
}
@article {pmid42356192,
year = {2026},
author = {Diaconu, IE and Onofrei, MI and Vâță, A and Roșu, FM and Ignat, EB and Cuciureanu, ID and Hurmuzache, ME and Luca, MC},
title = {Clinical and Inflammatory Predictors of Neurocognitive Decline in Long COVID: A Two-Year Longitudinal Study with Propensity Score Matching.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {6},
pages = {},
doi = {10.3390/medicina62061180},
pmid = {42356192},
issn = {1648-9144},
mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Longitudinal Studies ; Prospective Studies ; Propensity Score ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Middle Aged ; Aged ; Vitamin D/blood/analogs &amp; derivatives ; *Cognitive Dysfunction/etiology/blood ; SARS-CoV-2 ; Vitamin B 12/blood ; Biomarkers/blood ; Pandemics ; Inflammation ; },
abstract = {Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients' long-term quality of life. This study aimed to identify clinical and laboratory risk factors-including inflammatory markers and micronutrients-for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819-5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191-2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431-2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65-14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412-6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353-19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention.},
}
@article {pmid42356414,
year = {2026},
author = {Suárez-Moreno, N and Navarro-Matías, E and Arroyo-Romero, S and Navarro-Cáceres, A and Domínguez-Martín, A and Lugones-Sanchez, C and Gonzalez-Sanchez, S and Gómez-Marcos, MA and Gómez-Sánchez, M and Gómez-Sánchez, L and BioICOPER Investigators Group, },
title = {Dietary Macronutrient Intake and Vascular Health in Patients with Long COVID: The BioICOPER Study.},
journal = {Nutrients},
volume = {18},
number = {12},
pages = {},
doi = {10.3390/nu18122028},
pmid = {42356414},
issn = {2072-6643},
support = {PI25/00071//Institute of Health Carlos III/ ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Vascular Health ; *COVID-19/physiopathology/complications ; Carotid Intima-Media Thickness ; Vascular Stiffness ; *Nutrients/administration &amp; dosage ; Pulse Wave Analysis ; Energy Intake ; Post-Acute COVID-19 Syndrome ; *Diet ; Adult ; Dietary Carbohydrates/administration &amp; dosage ; SARS-CoV-2 ; Diet Records ; Aged ; Carotid-Femoral Pulse Wave Velocity ; },
abstract = {Background: Long COVID (LC) has been associated with persistent endothelial dysfunction and vascular impairment. Although nutrition is a key modifiable determinant of cardiovascular health, the relationship between dietary macronutrient intake and vascular alterations in LC remains poorly understood. Objective: To evaluate the association between dietary macronutrient intake and markers of vascular structure, arterial stiffness, and vascular aging in patients with LC, including potential sex differences. Methods: We conducted a cross-sectional study including 304 patients with LC. Dietary intake was assessed using a validated 7-day dietary record (EVIDENT study). Vascular evaluation included carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI), augmentation index adjusted to a heart rate of 75 beats per minute (AIx@75), and vascular aging index (VAI), measured using carotid ultrasound and validated devices (SphygmoCor[®] and VaSera[®]). Results: The mean age was 53 ± 12, higher in men (p = 0.001). The study included 207 women (68%) and 97 men (32%). Energy intake and carbohydrate intake in g/day showed a negative association with cfPWV in Model 2 (energy intake: β = -0.06; 95% CI: -0.11 to -0.01; p = 0.02; carbohydrate intake: β = -0.47; 95% CI: -0.87 to -0.07; p = 0.02). The percentage of carbohydrate/total energy intake was positively associated with AIx@75 in Model 2 (β = 0.8; 95% CI 0.12 to 1.49; p = 0.02), and percentage of fat/total energy intake showed a consistent inverse association (β = -0.30; 95% CI: -0.49 to -0.11; p = 0.002). No significant associations were observed for cIMT, baPWV, CAVI or VAI. Conclusions: In patients with LC, total energy intake and absolute carbohydrate intake were negatively associated with cfPWV, whereas the relative contribution of carbohydrates and fats to total energy intake showed divergent associations with AIx@75. These findings suggest that both absolute macronutrient intake and relative macronutrient distribution may be related to central arterial stiffness and wave reflection parameters LC. However, given the cross-sectional design of the study, these results should be interpreted as exploratory and do not allow causal inference. Further longitudinal and interventional studies are needed to confirm these findings and to assess whether nutritional strategies may contribute to modulating vascular risk in this population.},
}
@article {pmid42358486,
year = {2026},
author = {Schieffer, B},
title = {Redefining pandemic resilience: a roadmap for post-infectious syndrome preparedness and health system transformation.},
journal = {Frontiers in health services},
volume = {6},
number = {},
pages = {1779647},
pmid = {42358486},
issn = {2813-0146},
abstract = {Post-infectious syndromes like Long COVID and ME/CFS lead to disability and economic losses globally, especially in lower-income countries. These involve complex multisystem issues such as immune disturbances, inflammation, autonomic dysregulation, vascular problems, altered metabolism, and tissue damage. Re-infections increase the risk of disability and complications. Healthcare delays diagnosis and neglects long-term effects. We propose a three-part healthcare approach: primary care screening with digital tools, regional testing centers, and specialized Centers of Excellence for complex cases. An integrated infrastructure with registries, patient data, and wearables supports personalized care and surveillance. Policies should include disability benefits, rehab, infection control, and innovative funding. Healthcare must be accessible via mobile and community efforts, integrated into pandemic plans. The goal is to reduce morbidity and improve socioeconomic resilience.},
}
@article {pmid42361007,
year = {2026},
author = {Williams, SL and Beadle, E and Williams, P and Master, H and Casarin, A},
title = {A mixed-methods analysis of the implementation of a new community long-COVID service during the 2020 pandemic: Learning from practice.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0313367},
doi = {10.1371/journal.pone.0313367},
pmid = {42361007},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; Pandemics ; Male ; Cross-Sectional Studies ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; SARS-CoV-2 ; Aged ; Adult ; United Kingdom/epidemiology ; Referral and Consultation ; },
abstract = {INTRODUCTION: The rapidly increasing prevalence of long-COVID (LC), a condition characterised by multisystem complexity and high patient symptom burden, posed an immediate need to develop new clinics for assessment and management. This article reports on the rapid implementation of a reactive and responsive LC care pathway. We mapped patients' journeys through this pathway, identifying the services that were activated according to prevalent symptoms, and used the Theoretical Domains Framework (TDF) to assess the barriers and facilitators to its implementation and delivery, from the perspective of health care professionals (HCPs) and LC patients.<br><br>METHODS: Mixed methods study, including retrospective quantitative cross-sectional analysis of patient data and semi-structured qualitative interviews. One hundred and sixteen patients who attended the long-COVID clinic in Hertfordshire, UK, in the first 5 months of its existence and consented for their data to be analysed. Six HCPs and five patients participated in semi-structured interviews.<br><br>RESULTS: Patients were referred into the service an average of 5.75 months post initial COVID-19 infection. 82% of patients required onward referral to other HCPs, most commonly pulmonary rehabilitation, chronic fatigue specialists, and a specialist COVID-19 rehab general practitioner embedded within the service. Patients reported having rehabilitation needs, moderate depression and anxiety, and difficulties performing usual activities for daily living. The TDF domains most relevant to the implementation of the LC pathway were beliefs about capabilities, environmental context and resources, knowledge, and reinforcement.<br><br>DISCUSSION: Our study provides novel insight into the development of a reactive multidisciplinary care pathway. Key drivers for successful implementation of LC services were identified, such as leadership, multidisciplinary teamwork, transferable skills, and knowledge exchange. Barriers to rapid set up of the service included funding constraints and the rapid evolution of an emergency context.},
}
@article {pmid42362101,
year = {2026},
author = {Choi, Y and Jacobs, DR and Kramer, HJ and Coresh, J and Cushman, M and Reiner, AP and Demmer, RT and Tracy, RP and Sun, Y and Balte, PP and Raffield, LM and Min, YI and Vasan, RS and Xanthakis, V and Regan, EA and Kanaya, AM and Lash, JP and Umans, JG and Oelsner, EC},
title = {Associations of Pre-Pandemic CKD With Acute and Post-Acute COVID-19: The C4R Study.},
journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.ajkd.2026.04.011},
pmid = {42362101},
issn = {1523-6838},
abstract = {RATIONALE &amp; OBJECTIVE: While kidney failure is associated with severe COVID-19, data on early-stage chronic kidney disease (CKD) and its relationship to acute and post-acute COVID-19, as well as post-vaccination antibody responses, are limited. We evaluated pre-pandemic CKD stage in relation to these outcomes.<br><br>STUDY DESIGN: Prospective cohort.<br><br>SETTING &amp; PARTICIPANTS: Adults in nine US population-based studies established since 1971, with pre-pandemic CKD measurements and follow-up for COVID-19 outcomes.<br><br>EXPOSURE: CKD stages (low CKD stage [reference], moderate CKD stage, high CKD stage, and very high CKD stage) defined by creatinine-based eGFR and urinary albumin-to-creatinine ratio.<br><br>OUTCOMES: (i) COVID-19 hospitalization or death (self-report/medical records, 2020&#x2012;2023); (ii) RECOVER Long COVID Research Index score &#x2265;11 (LCRI-positivity by questionnaires, 2023&#x2012;2024); (iii) post-vaccination anti-Spike 1 (S1) IgG levels (dried blood spots, 2021&#x2012;2022).<br><br>ANALYTICAL APPROACH: Cause-specific hazards for severe COVID-19, logistic regression for LCRI-positivity, and generalized additive models for anti-S1 IgG.<br><br>RESULTS: Among 26,039 participants, CKD stage was low in 81.7%, moderate in 13.0%, high in 3.6%, and very high in 1.7%. Over a median 550-day follow-up (P25-P75: 314&#x2012;636), 734 had severe COVID-19; 12.1% of infected (669/5,527) were classified as LCRI-positive; and 3.1% (82/2,679) were anti-S1 IgG antibody non-reactive. A more severe CKD stage was associated with a greater risk for severe COVID-19: the HR for moderate stage CKD was 1.27 (95% CI, 1.03&#x2012;1.56), for high stage CKD, 2.33 (1.77&#x2012;3.06), and for very high stage CKD, 2.72 (1.88&#x2012;3.92). Higher CKD stages were associated with lower anti-S1 IgG levels: &#x2012;12.00% (95% CI: &#x2012;21.14% to &#x2012;1.78%) for moderate stage CKD, &#x2012;27.03% (95% CI, &#x2012;40.00% to &#x2012;11.25%) for high stage CKD, and &#x2012;48.9% (95% CI, &#x2012;61.60% to &#x2012;32.01%) for very high stage CKD. A higher prevalence of LCRI positivity was observed only among infected individuals with very high stage CKD (OR=2.20; 95% CI: 1.16&#x2012;4.18).<br><br>LIMITATIONS: Some outcomes were self-reported.<br><br>CONCLUSION: Higher CKD stages were associated with a greater risk for severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed between CKD stage and LCRI-positivity except in individuals with very high stage CKD.<br><br>INDEX WORDS: Chronic kidney disease, kidney dysfunction, SARS-CoV-2 infection, severe COVID-19, Long COVID, anti-S1 IgG antibody, Prospective cohort.},
}
@article {pmid41862744,
year = {2026},
author = {Kalansooriya, W and Serra-Sastre, V and Jofre-Bonet, M},
title = {Non-communicable diseases, COVID-19 and labour market outcomes.},
journal = {The European journal of health economics : HEPAC : health economics in prevention and care},
volume = {},
number = {},
pages = {},
pmid = {41862744},
issn = {1618-7601},
abstract = {The COVID-19 pandemic affected people with Non-Communicable Diseases (NCDs) in multiple ways. However, limited attention has been paid to its impact on labour outcomes for individuals with pre-existing NCDs. Given the heightened vulnerability of individuals with NCDs to COVID-19, the pandemic and related lockdown measures may have disproportionately influenced their employment prospects. Our study investigates the effects of the COVID-19 pandemic on the employment status and work hours of individuals with NCDs. We use data from the Understanding Society COVID-19 study in the UK, supplemented with main-stage Understanding Society surveys. We apply a difference-in-difference approach to estimate the pandemic’s impact on labour market outcomes over time. Our results indicate that COVID-19 significantly reduced both the likelihood of employment and working hours among individuals with NCDs relative to those without. These effects varied by age, gender, sector of employment (key workers vs. non-key workers), and type of NCDs. We further examine potential causes for the reduction in employment and working hours, and find that while the pandemic did not exacerbate existing health conditions among people with NCDs, their reduced labour market participation was largely driven by increased vulnerability to infection, the impact of long COVID, and the effects of public health interventions. Our study provides deeper insights into the post-pandemic contraction of the UK labour market, suggesting that the combined effects of NCDs and COVID-19 have contributed to a decline in workforce participation.},
}
@article {pmid41932971,
year = {2026},
author = {Lin, CJ and Bosco, AA and Alves, LI and Rosa, AA and da Silva, MER},
title = {Post-COVID-19 diabetes outcomes.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42284-7},
pmid = {41932971},
issn = {2045-2322},
support = {2022/01769-5//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
abstract = {Long-COVID-19 presentation has not been evaluated with proper depth in patients with diabetes (DM). This retrospective study evaluated 870 patients (320 DM, 550 non-DM) followed for up to 7.1 months post-hospitalization. Acute myocardial infarction, angina, articular edema, diarrhea, myocarditis/pericarditis were more frequent in patients with DM during the follow-up (p < 0.05). Recovery from COVID-19 symptoms was negatively associated with (89.8 × 94.27%; p = 0.038) while diarrhea, articular edema, abdominal pain, cardiovascular complications and worse health status were positively associated with DM. Patients with DM also had more frequent falls (21.1% × 11.1%; p = 0.0002033) and an increase in frailty scale score after COVID-19 (median of difference: 1 × 0; p = 6.124 × 10− 06). The quality of life of patients with diabetes was poorer with more frequent impaired mobility, inability to perform daily activity, discomfort and performed worse in physical and cognitive domains by WHODAS. Forty cases (7.3% of patients) of apparent new-onset diabetes were observed. Diabetes status did not affect the frequency of pain, skin problems, infections, newly diagnosed hypertension, abnormal lung sounds, post-COVID-19 hospital visit, anxiety and depression. Our data suggests a poorer outcome in diabetic patients and a 7.3% risk of diabetes progression in non-diabetic individuals up to 7.1 months after acute COVID-19.},
}
@article {pmid42342851,
year = {2026},
author = {Virrantaus, HR and Sirén, M and Varonen, M and Arokoski, J and Kanerva, M and Kvarnström, K and Malmivaara, A and Sainio, M and Juutistenaho, S and Sulg, A and Vangelova-Korpinen, V and Vuokko, A and Venäläinen, MS and Liira, H},
title = {The course and trajectories of quality of life among post-COVID-19 patients in the HUS long covid cohort study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-59199-y},
pmid = {42342851},
issn = {2045-2322},
support = {6248//Signe and Ane Gyllenberg's Foundation/ ; 101057553//Long Covid - HORIZON-HLTH-2021-DISEASE-04/ ; },
abstract = {Patients with post-COVID condition (PCC) frequently report reduced quality of life (QoL). This study assessed QoL and health-related QoL (HRQoL) with trajectories within a prospective PCC cohort. The study included adult patients at a PCC clinic. Outcomes were collected at 0, 3, 6, and 12 months. The primary outcome was QoL by Visual Analogue Scale (VAS 0-10). Secondary outcomes included QoL by EUROHIS-QOL-8 and HRQoL by 15D, and patients' symptom perceptions by Somatic Symptom Disorder - B Criteria Scale (SSD-12). Linear mixed models analyzed temporal changes, and trajectory analysis modeled recovery patterns. At baseline, 442 patients participated, with 305 (69.0%) providing follow-up data. Most patients (92.7%) were non-hospitalized. Trajectory analysis of EUROHIS-QOL-8 identified two recovering trajectories (73.8%) and a stable group (26.2%). Stable trajectories were associated with more comorbidities and higher levels of worry-inducing symptom perceptions (mean SSD-12 score 26 out of 48), whereas marked recovery was linked to being employed and having lower SSD-12 (10-13). Mean QoL improved over 12 months from 5.2 to 6.5 on the 0-10 VAS scale and from 3.1 to 3.5 on the EUROHIS-QOL-8 scale of 1-5. HRQoL by 15D increased from 0.76 to 0.80 (scale 0-1). In conclusion, patients with comorbidities and distressing illness beliefs are the most vulnerable group in rehabilitation and require specific attention.},
}
@article {pmid42343084,
year = {2026},
author = {Camargo, SM and Dos Santos, ALG and Maximo, ST and da Silva, KCB and de Oliveira Machado, B and Sassaki, CG and de Paula, SHB and Puglisi, JL and Goroso, DG},
title = {Assessing autonomic nervous system imbalance in long COVID-19 patients through heart rate variability during tilt testing.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-38800-4},
pmid = {42343084},
issn = {2045-2322},
support = {164066/2024-1//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 88887.941749/2024-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 2021/14231-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
abstract = {Long COVID-19 is recognized as a condition associated with autonomic nervous system (ANS) dysfunction. However, quantitative evidence of its impact on heart rate variability (HRV) and blood pressure (BP) regulation during postural changes remains limited. This study assessed autonomic imbalance in post-COVID-19 patients by evaluating HRV and BP responses during tilt table testing, comparing long COVID-19 patients with healthy controls. A total of 61 participants were enrolled, 39 long COVID-19 patients (Study Group, SG) and 22 healthy controls (Control Group, CG). HRV was analyzed using time- and frequency-domain parameters. BP monitoring evaluated systolic, and diastolic blood pressure (SBP, and DBP respectively), and Pulse pressure (PP = SBP-DBP) was calculated for each phase. SG participants exhibited marked autonomic dysfunction during tilt. In the upright phase, they showed a significant increase in mean RR intervals (p = 0.0136), reduced normalized low-frequency (LF[†]) with p = 0.0316, increased normalized high-frequency (HF[†]) with p = 0.0315, and a decreased low-frequency/high-frequency (LF/HF) ratio (p = 0.0316), indicating a blunted sympathetic response and impaired autonomic adaptation to orthostatic stress. BP responses were also impaired: SG demonstrated attenuated changes in PP (ΔPP) when transitioning from the upright position to the recovery phase (p < 0.037). Within-group analysis confirmed persistent RR interval instability (p < 0.0001), incomplete normalization of LF and HF components (both p < 0.0001), and delayed recovery of PP after return to supine position. BP responses were also diminished: SG showed smaller ΔPP when moving from standing upright to the recovery phase (p < 0.037). Baroreflex sensitivity values did not differ between groups. Long COVID-19 patients display significant autonomic dysregulation, characterized by reduced HRV, abnormal BP responses. These findings highlight the value of tilt testing in uncovering hidden dysautonomia and support the need for targeted interventions, including pharmacologic modulation and long-term HRV/BP monitoring, to improve cardiovascular stability in long COVID-19.},
}
@article {pmid42343157,
year = {2026},
author = {Vergara, XP and Gibb, K and Garvey, KM and Frederick, M and Harrison, R},
title = {Post-Acute COVID Among California Workers' Compensation Claims Filed in 2020-2022.},
journal = {Journal of occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/JOM.0000000000003803},
pmid = {42343157},
issn = {1536-5948},
abstract = {OBJECTIVES: To examine sociodemographic risk factors for post-acute COVID (PASC) among California workers' compensation (WC) claims in 2020-2022.<br><br>METHODS: We matched WC claims to SARS-CoV-2 test data, augmented with external sociodemographic data, and estimated odds ratios (OR) using logistic regression models.<br><br>RESULTS: PASC accounted for 7% of the 206,375 COVID and PASC cases. PASC cases were more commonly 30-49 years old, female, longer tenured, and in healthcare and protective service occupations compared to acute COVID. The highest PASC OR were among workers 50-69 years old, and workers of color, including non-Latino American Indian/Alaska Native, Black, Native Hawaiian/Pacific Island, and multiple races, and healthcare practitioners.<br><br>CONCLUSIONS: During the first three years of the COVID pandemic, PASC was common among workers with WC claims in CA and unevenly distributed, with observed disparities by age, race, and occupation.},
}
@article {pmid42343284,
year = {2026},
author = {Lerma-Irureta, D and Presa-Gutiérrez, E and Méndez-López, F and Vicente-García, C and Blasco-González, I and Magallón-Botaya, R},
title = {Biopsychosocial factors associated with health-related quality of life in long COVID: a matched case-control study in primary care.},
journal = {BMC primary care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12875-026-03445-9},
pmid = {42343284},
issn = {2731-4553},
support = {PI22/01070//Instituto de Salud Carlos III/ ; },
abstract = {BACKGROUND: Long COVID is associated with persistent symptoms, functional impairment, and reduced health-related quality of life (HRQoL), but the factors most strongly associated with poorer HRQoL remain incompletely characterized. This study compared adults with long COVID and recovered controls and identified variables independently associated with worse HRQoL.<br><br>METHODS: We conducted a case-control analysis of the ARALONGCOV 2022 dataset including 170 adults with prior COVID-19: 85 with long COVID and 85 recovered controls without persistent symptoms. HRQoL was assessed with the 12-item Short Form Health Survey (SF-12) total score. Additional measures included depressive symptoms (Patient Health Questionnaire-9, PHQ-9), fatigue severity (Fatigue Severity Scale, FSS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophizing, post-COVID functional status (PCFS), physical activity, and distance completed during the six-minute walk test (6MWT-D). Between-group comparisons used Mann-Whitney U tests for continuous variables and chi-squared or Fisher exact tests for categorical variables. Univariable and multivariable linear regression models were fitted within long COVID cases to identify factors independently associated with SF-12 total score.<br><br>RESULTS: Compared with recovered controls, participants with long COVID had markedly worse HRQoL (median SF-12 28.75 [IQR 21.25-39.17] vs 73.96 [62.81-77.50]; p&#x2009;<&#x2009;0.001), more depressive symptoms (PHQ-9: 12.00 [7.00-18.00] vs 2.00 [0.00-6.00]; p&#x2009;<&#x2009;0.001), greater fatigue (FSS: 57.00 [50.00-62.00] vs 13.00 [9.00-33.00]; p&#x2009;<&#x2009;0.001), worse sleep quality (PSQI: 14.00 [9.00-16.00] vs 6.00 [3.00-11.00]; p&#x2009;<&#x2009;0.001), and shorter 6MWT-D (481 [406-560] m vs 556 [491-609] m; p&#x2009;<&#x2009;0.001). Long COVID cases were also less frequently employed (38.8% vs 81.2%; p&#x2009;<&#x2009;0.001) and had more post-COVID comorbidity (88.2% vs 60.0%; p&#x2009;<&#x2009;0.001). In the multivariable model within long COVID cases (n&#x2009;=&#x2009;85), active employment was independently associated with better HRQoL (B 5.315, 95% CI 0.610 to 10.021; p&#x2009;=&#x2009;0.027), whereas depressive symptoms (B&#x2009;-&#x2009;1.124, 95% CI&#x2009;-&#x2009;1.500 to&#x2009;-&#x2009;0.748; p&#x2009;<&#x2009;0.001) and post-COVID comorbidity count (B&#x2009;-&#x2009;1.252, 95% CI&#x2009;-&#x2009;2.484 to&#x2009;-&#x2009;0.021; p&#x2009;=&#x2009;0.046) were independently associated with worse HRQoL. Fatigue severity showed a borderline association in the same direction (B&#x2009;-&#x2009;0.171, 95% CI&#x2009;-&#x2009;0.343 to&#x2009;+&#x2009;0.001; p&#x2009;=&#x2009;0.051). The model explained 48.9% of the variance in SF-12 score within long COVID cases (R[2]&#x2009;=&#x2009;0.489; adjusted R[2]&#x2009;=&#x2009;0.463). Exploratory clustering did not identify discrete phenotypes; the burden distribution was more consistent with a continuous severity gradient. For descriptive purposes, a lower-burden stratum (33/78, 42.3%) and a higher-burden stratum (45/78, 57.7%) were operationalized and differed across symptom load, fatigue, mood, functional status, exercise capacity, and HRQoL.<br><br>CONCLUSIONS: Long COVID was associated with profound impairment in HRQoL compared with recovered controls. Depressive symptoms, post-COVID comorbidity burden, and lower active employment were the strongest independent correlates of poorer HRQoL; fatigue severity showed a borderline association in the same direction. These findings support multidisciplinary long COVID care models that integrate symptom control, mental health assessment, and social and occupational reintegration. Routine assessment of fatigue, depressive symptoms, post-COVID multimorbidity, and occupational status may help identify long COVID patients with the most severe concurrent HRQoL impairment, though longitudinal confirmation is needed to establish predictive utility.<br><br>TRIAL REGISTRATION: Trial registration: ISRCTN registry, identifier ISRCTN27312680.},
}
@article {pmid42344094,
year = {2026},
author = {Senjam, SS and Bansal, G and Manna, S and Balhara, YPS and Gupta, Y and Ray, A and Lomi, N},
title = {Self-reported Long COVID and its Determinants in a Rural North Indian Adult Population: Lessons Learnt from the Pandemic.},
journal = {Indian journal of community medicine : official publication of Indian Association of Preventive &amp; Social Medicine},
volume = {51},
number = {3},
pages = {490-496},
pmid = {42344094},
issn = {0970-0218},
abstract = {BACKGROUND: Most studies on long COVID-19 symptoms (LCSs) are conducted in urban areas or hospital. To date, relevant evidence in LCS from community-based rural studies is lacking. Therefore, the present study aimed to investigate LCS and its determinants in a rural adult population of northern India.<br><br>METHODS: A cross-sectional study was conducted in a rural district, Jhajjar, Haryana in 2023. Forty clusters were covered from one randomly selected subdistrict. A semistructured questionnaire on the SurveyMonkey platform consisted of questions related to sociodemographic profile, health problems, pre-existing morbidity, LCS, and functional difficulties. The data regarding infection with COVID-19 were collected based on self-reported positive testing for SARS-CoV-2 on RT-PCR.<br><br>RESULTS: Out of the 3700 enumerated, 2954 (79.8%) were surveyed. The self-reported infection rate was 6.2% (183/2954, 95% CI: 5.3-7.1). Further, 23% (42/183, 95% CI: 17.01-29.7) of infected cases have LCS, whereas 1.4% (42/2954) of the study population have LCS. The prevalence of LCS was higher in females than in males (28.7% vs 17.7%). Weakness (14, 33.4%), weight loss (6,14.3%), memory problems (6, 14.3%), and headache (4, 9.5%) were common reported LCSs. Univariable analysis revealed a significantly lower risk of LCS in the age group of 26-35 years (OR 0.32, 95% CI: 0.10-0.83, P = 0.019). In contrast, higher risk was observed with lower education (OR 4.46, 95% CI: 1.47-13.78, P = 0.003), and pre-existing morbidities such as seeing difficulty (OR 2.91, 95% CI: 1.09-7.58, P = 0.021, difficulty in self-care (OR 3.72, 95% CI: 1.07-12.88, P = 0.021), and communication difficulties (OR 5.28, 95% CI: (0.76-45.74, P = 0.046).<br><br>CONCLUSION: A higher probability of LCS is found among females of older age, participants with lesser education, and pre-existing comorbidities.},
}
@article {pmid42344734,
year = {2026},
author = {Ren, Z and Liu, X and Sun, W and Gao, X and Jiang, W and Li, Y and Hu, C and Zhu, M and Zhao, Y and Li, Y and Xia, X and Yang, Z and Liu, J and Lv, X and Wang, T and Cui, D},
title = {Recombinant RBD-based subunit vaccines incorporating high-frequency mutation sites elicit cross-immunity and robust protection against SARS-CoV-2.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1806270},
pmid = {42344734},
issn = {1664-302X},
abstract = {INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), a highly pathogenic coronavirus (CoV) belonging to Coronavirus B, has triggered outbreaks or pandemics. Currently, many variants of SARS-CoV-2 have evolved, which exhibit severe immune evasion and imprinting resistance to existing vaccines and cause infected individuals to develop Post-Acute Sequelae of SARS-CoV-2 (also termed Long-COVID). This underscores the public health importance of developing effective vaccines with broad-spectrum efficacy against the SARS-CoV-2 variant and other CoVs with pandemic potential.<br><br>RESULTS: In this study, we expressed three tandem-repeat dimeric recombinant RBD proteins using an insect-baculovirus expression system integrated with the high-frequency SARS-CoV-2 RBD mutation sites. We performed immunogenicity assessment and attack protection tests. The date showed that these innovative SARS-CoV-2 RBD recombinant protein vaccines could show varying degrees of cross-immunity response and potent protection against SARS-CoV-2.<br><br>CONCLUSION: Overall, our results indicated that these recombinant RBD subunit vaccines could serves a promising platform for a universal vaccine against SARS-CoV-2 and its variants, and provide a new perspective for the design of other future pandemic vaccines.},
}
@article {pmid42346057,
year = {2026},
author = {Srikanth, S and Ivankovic, D and Gonzales, L and Dean, D and Boccuto, L},
title = {Cellular Metabolic Signatures of Long COVID-19.},
journal = {Infectious disease reports},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/idr18030050},
pmid = {42346057},
issn = {2036-7430},
support = {186306677//Clemson University/ ; },
abstract = {BACKGROUND/OBJECTIVES: Long COVID-19 (LC-19), also known as Post-Acute COVID-19 Syndrome (PACS), is a chronic condition some people experience after an initial SARS-CoV-2 infection. The etiology of this complex, multifactorial disease remains largely unknown, although various theories have been propounded. This study aims to profile and compare the metabolic activity of cells of normal and LC-19 patients.<br><br>METHODS: A cohort of 20 individuals, 10 with LC-19 and 10 without LC-19, was selected based on their post-COVID-19 symptomatology. Saliva was tested for opportunistic viruses like Epstein-Barr virus (EBV) and Human Herpesvirus 6 (HHV-6). Lymphoblastoid cell lines derived from blood were analyzed using the Biolog Phenotype Mammalian Microarrays (PM-M1, PM-M6, and PM-M7) to assess metabolic activity across a wide array of growth substrates and effector molecules.<br><br>RESULTS: Unique metabolic profiles emerged across the controls and LC-19 groups. The SARS-CoV-2 infection causes an over two-fold enhanced utilization of glycolytic and anaerobic substrates and a reduced response to growth factors and effectors. The increased energy source utilization assessed in PM-M1 is unsustainable, and the LC-19 groups demonstrate this with a clear correlation with the number of LC-19 symptoms, demonstrating a trend consistent with metabolic reprogramming. The infection also results in a reduced response to growth factors and effectors, assessed in PM-M6 and PM-M7, with the level of reduction commensurate with the symptom burden.<br><br>CONCLUSIONS: The data from the patient groups were analyzed and compared to construct a metabolic profile unique to individuals who developed LC-19, which could, in the future, be used for diagnosis and to identify targets for therapeutic intervention. Our study identified an LC-19-specific metabolic profile indicative of adaptive responses to stress, cellular dysfunction, and prolonged inflammation, leading to the reprogramming of bioenergetic pathways.},
}
@article {pmid42346188,
year = {2026},
author = {Lică, IMO and Țincu, IF and Drăgănescu, AC and Pleșca, DA},
title = {Factors Associated with Long COVID in the Pediatric Population: A Retrospective Case-Control Study.},
journal = {Clinics and practice},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/clinpract16060105},
pmid = {42346188},
issn = {2039-7275},
abstract = {Background: Long COVID in children is increasingly recognized, yet its clinical predictors and objective biological correlates remain insufficiently characterized. Objectives: The objective was to compare clinical, demographic, and laboratory characteristics between children with and without long COVID and to identify associated variables. Methods: We conducted a retrospective observational case-control study at the "Dr. Victor Gomoiu" Children's Clinical Hospital, including pediatric patients with confirmed SARS-CoV-2 infection. Cases were defined as children with symptoms persisting ≥12 weeks after acute infection, while controls had no persistent symptoms at ≥12 weeks. Results: Eighty-nine children with long COVID and 88 matched controls were included. Children with long COVID were significantly older (1.79 ± 0.90 vs. 1.14 ± 0.80 years, p < 0.001) and more frequently from urban areas (86.5% vs. 69.3%, p = 0.0099). Lymphocyte, monocyte, and basophil counts were significantly lower in the Long COVID group, while D-dimer, ferritin, serum iron, urea, and creatinine levels were significantly higher. A multivariate predictive model demonstrated excellent discrimination (AUC = 0.94), with optimal sensitivity (84.3%) and specificity (89.8%) at a probability threshold of 0.48. Conclusions: Long COVID in children was associated with identifiable clinicobiological features. An exploratory composite model showed good discrimination but requires external validation.},
}
@article {pmid42349233,
year = {2026},
author = {Lv, F and Chen, Y and Xia, Y},
title = {Neurological sequelae of Long COVID: Pathophysiological mechanisms, diagnostic advances, and therapeutic perspectives.},
journal = {Journal of neuroimmunology},
volume = {419},
number = {},
pages = {579010},
doi = {10.1016/j.jneuroim.2026.579010},
pmid = {42349233},
issn = {1872-8421},
abstract = {SARS-CoV-2 infection may result in persistent neuropsychiatric symptoms beyond the acute phase, often discussed under the umbrella term "Long COVID". These manifestations commonly include mood disturbances, post-traumatic stress symptoms, cognitive impairment, sleep disturbances, and fatigue, with substantial effects on daily functioning and quality of life. Despite these concerns, the pathophysiological mechanisms underlying these sequelae remain poorly understood, and the lack of specific biomarkers hampers the development of targeted interventions. This review synthesizes recent advances in the clinical presentation, underlying mechanisms, diagnostic approaches, and therapeutic strategies for neuropsychiatric sequelae of Long COVID. We also discuss current challenges and outline future research priorities to facilitate the establishment of standardized diagnostic criteria and the development of effective, mechanism-based therapies.},
}
@article {pmid42350021,
year = {2026},
author = {Nairn, B and Walz, ID and Nikitas, C and Kaski, D and Utoomprurkporn, N and Maurer, C and Kikidis, D and Tsakanikas, V and Fotiadis, D and Pavlou, M and Bamiou, DE},
title = {Investigating the feasibility and acceptability of the TeleRehabilitation of balance clinical and economic Decision Support System (TeleRehaB DSS) in adults at risk of falls: study protocol for a multicentre clinical trial.},
journal = {BMJ open},
volume = {16},
number = {6},
pages = {e108821},
doi = {10.1136/bmjopen-2025-108821},
pmid = {42350021},
issn = {2044-6055},
abstract = {INTRODUCTION: Falls are a significant concern for older adults, particularly those with neurological, vestibular, cognitive and post-viral conditions, due to dizziness and imbalance. Conventional balance rehabilitation programmes, though effective, face challenges in adherence and accessibility. The TeleRehabilitation Decision Support System (TeleRehaB DSS) uses artificial intelligence (AI) and motion tracking to provide individualised multisensory balance rehabilitation (MBR) remotely. This trial aims to evaluate the acceptability, feasibility, safety and preliminary efficacy of a home-based TeleRehaB DSS among community-dwelling older adults at risk of falls due to stroke, mild cognitive impairment (MCI), long COVID and vestibular dysfunction.<br><br>METHODS AND ANALYSIS: This multicentre, assessor-blinded randomised controlled trial will recruit 460 community-dwelling adults aged 40-80 years with stroke, MCI, vestibular dysfunction or long covid across five sites in the UK, Europe and Southeast Asia. Participants will be randomised to a 9-week remotely supervised home exercise programme using either TeleRehaB DSS (high-tech or low-tech MBR with exergames and cognitive training) or standard care (OTAGO home exercise programme or Meniere's Dizziness booklet). Primary outcomes include feasibility, acceptability and safety, alongside clinical measures of balance and health-related quality of life (Functional Gait Assessment, EuroQol five-dimensional descriptive system instrument). Secondary outcomes assess balance, cognition, physical activity, dizziness, psychological well-being, fatigue and confidence. Usability, user experience and digital health literacy will also be evaluated. Anonymised data will undergo quality checks and be analysed using descriptive and exploratory statistics, mixed-effects models, cost-effectiveness analysis (incremental cost-effectiveness ratio) and thematic analysis of qualitative interviews, adjusting for site and relevant confounders.<br><br>ETHICS AND DISSEMINATION: This study has received institutional ethical approvals in the UK, Germany, Greece and Thailand and from Madeira, Portugal. Findings from this study will be submitted for peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: NCT06534164.},
}
@article {pmid42350777,
year = {2026},
author = {Leão, FC and Prazeres, CLS and Godoy, MDCL and Leite, CC and Cassol, DF and Soares, ALG and Gomes Junior, AM and Voegels, RL and Otaduy, MCG and Pinna, FR},
title = {Functional and structural olfactory changes in post-COVID-19 patients detected by 7 Tesla MRI.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-59851-7},
pmid = {42350777},
issn = {2045-2322},
support = {2022/03639-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
abstract = {Persistent olfactory dysfunction after SARS-CoV-2 infection is common, yet its central neural profile remains poorly defined. We combined ultra-high-field 7 Tesla resting-state functional MRI with surface-based cortical morphometry to characterise olfactory-network organisation and cortical structure in long-term post-COVID dysosmia. Thirty adults (14 with persistent dysosmia; 16 normosmic controls) completed psychophysical olfactory testing and 7 Tesla imaging. Connectivity analyses across 56 olfaction-related regions revealed a coherent pattern centred on insular, orbitofrontal and thalamic nodes: connectivity was reduced between the insula and the orbitofrontal and entorhinal cortices, and between the ventral posterior thalamus and the ventral insula, and increased between interhemispheric orbitofrontal regions and among anterior thalamic nuclei. Significant connections were predominantly right-lateralised or interhemispheric. Morphometry showed no volumetric differences but selective left orbitofrontal thinning. Across the whole sample, greater orbitofrontal and insular thickness was associated with better olfactory performance; however, this reflected the difference between patients and controls rather than a graded relationship within the patient group, and did not persist after accounting for group and age. Together, these findings provide a preliminary, proof-of-concept characterisation of an orbitofronto-insular signature of long-term post-COVID dysosmia and nominate candidate imaging markers for testing in larger, multi-centre cohorts.},
}
@article {pmid42336872,
year = {2026},
author = {Changela, S and Katz, R and Shah, J and Henry, SS and Duong, TQ},
title = {Risk of new-onset obstructive sleep apnea up to 4.5 years after COVID-19 in the urban population.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-56469-7},
pmid = {42336872},
issn = {2045-2322},
abstract = {Obstructive sleep apnea (OSA) is linked to cardiovascular, metabolic, and cognitive morbidity. Although COVID-19 has been associated with long-term respiratory and neurological sequelae, its role in precipitating new-onset OSA remains unclear. We evaluated whether SARS-CoV-2 infection increases risk of developing OSA up to 4.5 years post-infection and how risk varies by hospitalization status, demographics, comorbidities, and vaccination status. This retrospective cohort study used electronic health records from the Montefiore Health System in the Bronx. Adults tested for SARS-CoV-2 between March 1, 2020, and August 17, 2024, were classified as hospitalized COVID+ , non-hospitalized COVID+ , or COVID- . Patients with prior OSA or loss to follow-up were excluded. Inverse probability weighting adjusted for demographic, clinical, socioeconomic, and vaccination covariates. New-onset OSA was assessed using weighted Cox proportional hazards models. Secondary outcomes including hypertension, myocardial infarction, heart failure, stroke, arrhythmia, pulmonary hypertension, type 2 diabetes, and obesity of individuals who developed new-onset OSA were evaluated with Poisson regression. Sensitivity analysis used a pre-pandemic control cohort. Among 910,393 eligible patients, hospitalized [HR 1.41 (95% CI 1.14-1.73)] and non-hospitalized [HR 1.33 (95% CI 1.22-1.46)] COVID+ patients had higher adjusted risk of new-onset OSA versus COVID- controls. Similar findings were observed when compared to the historical controls (n = 621,046). After OSA onset, hospitalized COVID+ patients had higher risks of heart failure and pulmonary hypertension, while non-hospitalized COVID+ patients had higher risk of obesity vs COVID- patients. SARS-CoV-2 infection is independently associated with increased risk of new-onset OSA. These findings support targeted screening post-COVID in high-risk populations.},
}
@article {pmid42337098,
year = {2026},
author = {Kunc, P and Fabry, J and Mazuchova, J and Pec, M and Pecova, R},
title = {Serological Profiling and Neuro-Immune Resilience: The Dissociation Between Anti-SARS-CoV-2 Antibodies and Post-Viral Airway Hyperresponsiveness in Pediatric Asthma.},
journal = {Lung},
volume = {204},
number = {1},
pages = {},
pmid = {42337098},
issn = {1432-1750},
mesh = {Humans ; Child ; Female ; Male ; *Asthma/immunology/physiopathology/drug therapy ; Prospective Studies ; *COVID-19/immunology/complications/physiopathology ; *SARS-CoV-2/immunology ; Immunoglobulin G/blood/immunology ; Immunity, Humoral ; *Antibodies, Viral/blood/immunology ; Post-Acute COVID-19 Syndrome ; Chronic Cough ; Capsaicin ; Immunoglobulin A/blood/immunology ; Cough/physiopathology ; },
abstract = {BACKGROUND: Chronic cough is a frequent symptom of pediatric Long COVID, hypothetically driven by viral neurotropism and sensory nerve sensitization. We investigated the neuro-immune axis in pediatric asthma to determine if the magnitude of post-SARS-CoV-2 humoral immunity correlates with objective airway afferent nerve hypersensitivity.<br><br>METHODS: This prospective observational study included 61 pre-pubertal children (aged 8 to&#x2009;<&#x2009;12&#xa0;years) with well-controlled, predominantly inhaled corticosteroid (ICS)-treated (93.4%) bronchial asthma and confirmed past SARS-CoV-2 infection. Systemic humoral memory was quantified via anti-Spike IgG and IgA titers. Objective cough reflex sensitivity was measured using a capsaicin challenge test, establishing C2 and C5 values. Subjective symptom burden was evaluated using parent-proxy questionnaires (PCQ, VAS, PedsQL).<br><br>RESULTS: Stratification by median anti-Spike IgG (125.77 BAU/ml) revealed no significant differences in basal (C2, p&#x2009;=&#x2009;0.301) or motor response (C5, p&#x2009;=&#x2009;0.714) capsaicin thresholds between robust and waning humoral memory states. IgA stratification yielded identical results. Spearman's correlation confirmed a complete lack of association between absolute IgG titers and neurophysiological markers (p&#x2009;>&#x2009;0.05). Crucially, parent-reported chronic cough severity (PCQ, VAS) and asthma-specific quality of life demonstrated a complete dissociation from objective capsaicin thresholds across all evaluated domains (all p&#x2009;>&#x2009;0.05). Supplementary subgroup analysis revealed no significant differences in cough thresholds based on acute COVID-19 severity (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: A robust post-viral humoral immune response to SARS-CoV-2 does not precipitate peripheral airway nerve hypersensitivity in properly controlled, ICS-treated asthmatic children. The complete uncoupling of subjective parent-reported symptoms from objective neurophysiology cautions against diagnosing neurogenic Long COVID based solely on questionnaires, emphasizing the necessity of objective testing and evaluation of alternative atopic etiologies.},
}
@article {pmid42339247,
year = {2025},
author = {Mosabbir, A and Meltzer, JA and Uryash, A and Beroncal, EL and Andreazza, AC and Bartel, L},
title = {Cognitive rehabilitation among long COVID patients using vibratory and auditory treatment (VAT) is linked to BDNF.},
journal = {Frontiers in cognition},
volume = {4},
number = {},
pages = {1692578},
pmid = {42339247},
issn = {2813-4532},
abstract = {Cognitive dysfunction occurs in around 40% of long COVID (LC) patients, and in many cases appears second only to fatigue in prevalence. Vibratory and auditory treatment (VAT) within the gamma range has demonstrated improvements in symptoms associated with cognition and fatigue. In this open-label pilot study, we tested the effects of VAT on measures of cognition and fatigue in LC. Twenty patients were randomly divided into a treatment and a control group. Symptoms were monitored remotely through mobile apps and in-person visits before and after the treatment period. The treatment group received a device generating 40 Hz of VAT to take home and use every day from Monday to Friday for 4 weeks (i.e., 20 sessions over 28 days), whereas the control group did not use any device but followed the same data collection procedures. This study found that after 4 weeks of VAT, participants with LC exhibited increased performance in selective attention and response inhibition, an increased amount of circulating brain-derived neurotrophic factor (BDNF), and a reduced resting heart rate. We propose that VAT may be a useful rehabilitative tool for LC as well as other targeted populations that seek improvements in cognition or general health but are compromised immunologically or physically.},
}
@article {pmid42339267,
year = {2026},
author = {Green, TD and McWilliams, C and de Figueiredo, L and Soares, L and Pollack, B and Cohen, AK and Zhi-Xuan, T and Falor, T and Davis, HE},
title = {Algorithm dependence of patient phenotypes in Long COVID: a patient-led, multi-method clustering of 6031 patients using 162 self-reported symptoms.},
journal = {Oxford open immunology},
volume = {7},
number = {1},
pages = {iqag010},
pmid = {42339267},
issn = {2633-6960},
abstract = {OBJECTIVES: Long COVID, characterized by symptoms that remain or emerge in the months after acute COVID-19 infection, is a multisystemic condition with highly variable patient presentations. Phenotyping studies have reported divergent symptom clusters, increasingly used to design trials and interpret biomarker data. However, robustness of these clusters across analytic methods remains uncertain.<br><br>METHODS: We analyzed data from 6&#x2009;031 adults with&#x2009;&#x2265;&#x2009;90&#x2009;days of illness from a patient-led international survey. Participants reported presence/absence of 162 symptoms, post-exertional malaise severity and demographics. We applied three unsupervised machine learning approaches to the same symptom matrix, evaluating the resulting clusterings for concordance, robustness to subsampling, and relationship to symptom burden, post-exertional malaise severity, age and gender.<br><br>RESULTS: Each method produced clinically plausible symptom clusters, but concordance across methods was low. All three approaches identified a high-symptom-burden group enriched for post-exertional malaise severity, and lower-symptom-burden groups with older mean age and a lower proportion of women. Symptom count consistently correlated with higher post-exertional malaise severity and a greater proportion of women. Manifold analysis revealed that the overall symptom space was largely continuous, lacking clear cluster boundaries.<br><br>CONCLUSIONS: The strong dependence of patient clusters on algorithm choice suggests that single-method Long COVID phenotyping may produce incomplete or unstable subgroup definitions. Clustering methods may impose artificial boundaries on a smoothly varying symptom landscape, especially in studies capturing fewer symptoms. Phenotyping efforts should assess clustering robustness and avoid overinterpreting single-method results. Our multi-method analysis highlights the importance of considering the full breadth of patient symptoms when evaluating treatments.},
}
@article {pmid42339932,
year = {2026},
author = {Theodoro, EL and Prediger, KM and Damacena, MA and Silva, CVD and Cano, RDN and Uehara, SCDSA},
title = {Oral manifestations associated with long COVID: a scoping review.},
journal = {Revista brasileira de enfermagem},
volume = {79},
number = {},
pages = {e20250198},
doi = {10.1590/0034-7167-2025-0198},
pmid = {42339932},
issn = {1984-0446},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Mouth Diseases/etiology/epidemiology ; Quality of Life ; SARS-CoV-2 ; Female ; },
abstract = {OBJECTIVES: to map scientific evidence on oral manifestations originating during long COVID.<br><br>METHODS: this is a scoping review based on the method described by JBI. Primary articles published in Portuguese, English, and Spanish between March 2020 and December 2024 were included from the PubMed, Web of Science, Virtual Health Library, Scopus, Excerpta Medica dataBASE, and Scientific Electronic Library Online databases, and a descriptive analysis was performed.<br><br>RESULTS: of the 15 studies analyzed, the most frequent oral manifestations of long COVID were taste alterations, xerostomia, difficulty chewing, gingival bleeding, periodontitis, and changes in the teeth.<br><br>CONCLUSIONS: an association between long COVID and various oral manifestations was evidenced, impacting the quality of life of patients. Factors such as age, comorbidities, and social inequalities influence the persistence of these manifestations, with a higher prevalence in women. Multiprofessional collaboration and clearer guidelines are essential to improve dental care.},
}
@article {pmid42340243,
year = {2026},
author = {Epsi, NJ and Richard, SA and Morris, MJ and Lindholm, DA and Ganesan, A and Colombo, RE and Mende, K and Jones, MU and Malloy, AMW and Rubin, LH and Agan, BK and Tribble, DR and Burgess, TH and Dalgard, C and Puskarich, MA and Pollett, SD},
title = {Is cellular senescence a biological feature of Long COVID? A transcriptomic analysis across comparative post-acute sequelae phenotypes.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag315},
pmid = {42340243},
issn = {1537-6613},
abstract = {INTRODUCTION: Cellular senescence, involving cell-cycle arrest and inflammatory factor release, may play a role in Long COVID development. We investigated the role of senescence-associated genes across multiple post-acute sequelae phenotypes.<br><br>MATERIALS AND METHODS: Participants from a cohort study were grouped into post-COVID-19 groups: (i) sensory, fatigue/difficulty thinking, and difficulty breathing/exercise intolerance, identified through a machine learning (ML) analysis of symptom data; (ii) cognitive impairment, measured using a screening cognitive assessment tool (BRACE); and (iii) persistent dyspnea, identified using a symptom-scale known to correlate with a six-minute-walk-test. Post-infection whole blood samples underwent transcriptomic analysis with 47,125 genes used as the reference signature for gene set enrichment analysis (GSEA) against the SenMayo cellular-senescence query gene set (n = 125); enrichment were based on normalized enrichment scores (NES).<br><br>RESULTS: SenMayo genes were significantly upregulated in the early post-infection period in (a) 56 individuals who subsequently developed Long COVID symptom phenotypes, compared to 104 who did not develop Long COVID symptoms (NES = 6.04, P = 0.001); (b) 32 individuals with long-term cognitive impairment compared to 40 without long-term cognitive impairment measured by BRACE (NES = 2.58, P = 0.032); and (c) 26 participants who had persistent dyspnea compared to 53 without persistent dyspnea measured by the validated dyspnea instrument (NES = 6.29, P = 0.001). ETS2 was upregulated across all impairment-related phenotypes, while other SenMayo genes showed phenotype-specific variability.<br><br>CONCLUSIONS: This study suggests a role of senescence-associated genes in the development of Long COVID, including shared and unique transcriptomic patterns across phenotypes.},
}
@article {pmid42341208,
year = {2026},
author = {Dasarathy, D and Luk, JW and Shui, AM and Wong, RJ and Cheung, R and Monto, A and Ostacher, MJ and Batki, SL and Snyder, HR and Peluso, MJ and Satre, D and Khalili, M},
title = {Evaluating acute and post-acute COVID-19 symptoms among patients with and without alcohol-related cirrhosis: implications for quality management.},
journal = {Alcohol and alcoholism (Oxford, Oxfordshire)},
volume = {61},
number = {4},
pages = {},
doi = {10.1093/alcalc/agag043},
pmid = {42341208},
issn = {1464-3502},
support = {R01AA029312//National Institute of Alcohol Abuse and Alcoholism/ ; K24AA022523//National Institute of Alcohol Abuse and Alcoholism/ ; K24AA025703//National Institute of Alcohol Abuse and Alcoholism/ ; P30DK026743//National Institute of Alcohol Abuse and Alcoholism/ ; //the Intramural Research Program of the National Institutes of Health/ ; },
mesh = {Humans ; Female ; Male ; Aged ; *Quality of Life ; *Liver Cirrhosis, Alcoholic/complications/psychology/epidemiology ; Middle Aged ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Symptom Burden ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Patient-reported symptoms following COVID-19 exposure have been understudied in cirrhosis. This study evaluated type, severity, and persistence of symptoms along with impact on quality of life (QOL) post-SARS-CoV-2 infection in a cohort with and without alcohol-related cirrhosis.<br><br>METHODS: Patients with cirrhosis receiving care in hepatology clinics at three institutions were surveyed for symptoms and liver disease QOL (LDQOL) using standardized instruments following SARS-CoV-2 infection. Acute (<30&#xa0;days), post-acute (&#x2265;30&#xa0;days since onset), and Long COVID (&#x2265;3&#xa0;months) symptoms were compared by cirrhosis etiology and decompensated status. Associations between severe COVID-19 symptoms and LDQOL were examined using multivariable models.<br><br>RESULTS: 156 patients with prior COVID-19 exposure had a median age of 66.5&#xa0;years; 18% were female; 43% had alcohol-related liver disease (ALD); and 42% decompensated cirrhosis. Among 208 surveys conducted, the median (Q1, Q3) number of symptoms reported was 6 (3, 10), with 66% reporting at least one severe/very severe symptom and 21% had Long COVID. There were no significant differences in symptoms by cirrhosis etiology or decompensation except those with ALD had higher post-acute symptoms compared to non-ALD (RR 2.17, P&#x2009;=&#x2009;.04). Moreover, the total number of severe symptoms was inversely associated with LDQOL. For each additional severe symptom reported, LDQOL decreased by 1.12 points after adjusting for age, sex, ALD, decompensated cirrhosis, and MELD-Na score (95% CI -1.70 to -0.53, P&#x2009;=&#x2009;.001).<br><br>CONCLUSIONS: Assessing severity and persistence of post-COVID-19 exposure symptoms can help clinicians address patient-reported QOL concerns, optimize cirrhosis management, and inform integrated care for ALD and AUD.},
}
@article {pmid42341950,
year = {2026},
author = {Giunta, S and Sabbatinelli, J and Olivieri, F and Giuliani, A},
title = {Aging-related autonomic nervous system imbalance and adrenergic regulation of immunity: Implications for inflammaging, autoimmunity, and long COVID.},
journal = {Frontiers in neuroendocrinology},
volume = {},
number = {},
pages = {101269},
doi = {10.1016/j.yfrne.2026.101269},
pmid = {42341950},
issn = {1095-6808},
abstract = {The autonomic nervous system (ANS) plays a central role in immune homeostasis by integrating sympathetic and parasympathetic signals that regulate inflammation, immune cell trafficking, and tolerance. Aging is associated with a progressive autonomic imbalance characterized by sympathetic overactivation, reduced parasympathetic tone, and impaired β-adrenergic signaling in immune cells, which together contribute to inflammaging and immune dysregulation. In this review, we discuss how aging-related alterations in adrenergic pathways affect immune cell differentiation and cytokine networks, with particular emphasis on β2-adrenergic control of the Th17/regulatory T cell balance through cAMP-dependent mechanisms interacting with cytokine-driven STAT signaling. Chronic sympathetic stimulation and β-adrenergic desensitization weaken these regulatory constraints, favoring pro-inflammatory immune trajectories and loss of immune tolerance. Finally, we propose Long COVID as a paradigmatic condition in which pre-existing inflammaging and autonomic vulnerability are amplified by viral infection, leading to persistent inflammation, impaired immune regulation, and increased susceptibility to autoimmune manifestations.},
}
@article {pmid42342277,
year = {2026},
author = {Dennis, C and Alwan, NA},
title = {What does it mean to recover from long covid?.},
journal = {BMJ (Clinical research ed.)},
volume = {393},
number = {},
pages = {e100054},
doi = {10.1136/bmj-2026-100054},
pmid = {42342277},
issn = {1756-1833},
}
@article {pmid42342534,
year = {2026},
author = {Mulet, A and Signes-Costa, J and Fernández-Fabrellas, E and Ros, JA and Rodríguez-Portal, JA and Andreu, AL and Pallardó, F and González-Cabo, P},
title = {Mitochondrial Dysfunction and Telomeric Shortening as Long-term Complications After COVID-19.},
journal = {Archivos de bronconeumologia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.arbres.2026.03.018},
pmid = {42342534},
issn = {1579-2129},
abstract = {OBJECTIVES: To evaluate the potential role of telomere shortening and mitochondrial dysfunction in the development of long-term complications of COVID-19, including pulmonary fibrosis.<br><br>METHODS: We analyzed 132 patients from the prospective COVID-FIBROTIC cohort 1 year after hospitalization for bilateral pneumonia. Leukocyte telomere length was measured and compared with that of 78 age- and sex-matched controls. Fibrosis biomarkers and radiological findings were assessed at 2 and 12 months. In a subgroup of 44 patients, mitochondrial protein expression was evaluated 2 years after infection using reverse-phase protein arrays. Associations among telomere length, mitochondrial proteins, inflammatory markers, and fibrotic sequelae were analyzed.<br><br>RESULTS: Leukocyte telomere length was significantly shorter in patients than in controls (AUC, 0.84; P<.0001), independent of age or acute disease severity. At 12 months, 29% of patients showed fibrotic lung changes on HRCT. Elevated periostin and IL-6 levels correlated with persistent mitochondrial protein alterations at 2 years. Mitochondrial proteins such as ETF&#x3b2; and PKM2 differentiated patients with fibrotic sequelae and those with marked telomere attrition, suggesting their role as biomarkers. Moreover, in patients with fibrosis, telomere shortening correlated inversely with ACO1 levels, a protein involved in oxidative stress and iron metabolism.<br><br>CONCLUSIONS: SARS-CoV-2 infection induces sustained telomere shortening and long-term mitochondrial dysfunction, both of which are associated with fibrotic sequelae. These findings support a pathogenic link among mitochondrial dysregulation, telomere attrition, and pulmonary fibrosis, resembling mechanisms described in idiopathic pulmonary fibrosis. Monitoring these biomarkers may help identify patients at risk of chronic post-COVID complications.},
}
@article {pmid42331642,
year = {2026},
author = {Guedj, E and Verger, A and Horowitz, T},
title = {Brain [18F]FDG PET in Subjective Cognitive Complaints: From Diagnostic Gap to Neurobiological Insight.},
journal = {PET clinics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cpet.2026.05.004},
pmid = {42331642},
issn = {1879-9809},
abstract = {Subjective cognitive complaints are heterogeneous and may occur with normal, subtle, or objectively abnormal cognitive testing. Fluorodeoxyglucose (FDG) PET can help explore their metabolic substrate, particularly in subjective cognitive decline within the Alzheimer's disease continuum. In mild traumatic brain injury and long coronavirus disease (COVID), available studies suggest possible metabolic-network abnormalities but involve more heterogeneous populations and should be interpreted cautiously within multimodal, clinically characterized frameworks.},
}
@article {pmid42332203,
year = {2026},
author = {Akbar, N and Phadke, S and Mehelay, S and Fakolade, A and Finlayson, M},
title = {Symptoms, Functional Impact and Perceived Healthcare Barriers Experienced by Racialized Communities Living with Long COVID in Canada: A Mixed-methods Study.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {42332203},
issn = {2196-8837},
abstract = {BACKGROUND: Post COVID-19 Condition (PCC) or Long COVID has been shown to be more prevalent among racialized communities. The symptoms and lived experiences of racialized communities living with Long COVID in Canada has yet to be reported.<br><br>OBJECTIVE: To describe the symptoms, functional impact, and perceived barriers and facilitators to treatment and/or rehabilitation for racialized communities living with Long COVID in Canada. To further explore whether there are differences across racial groups (including comparison to non-racialized/ White) with regards to symptoms, functional impact, and perceived healthcare barriers.<br><br>METHODS: Convergent parallel mixed-methods design, which included quantitative measures and qualitative semi-structured interviews with 49 participants, with a large proportion (59%) of participants self-identifying as racialized (predominantly Black and South Asian).<br><br>RESULTS: The rates of severe fatigue and clinically significant depression for the entire sample were high at 88% and 78% respectively. Long COVID had major negative functional impacts, with 27% of participants not being able to return to full-time work since contracting COVID-19. The biggest barrier to treatment and rehabilitation was dismissal by healthcare providers, which was exacerbated by factors including gender identity (being a woman) and race. Black participants reported more discrimination compared to White participants, which correlated with more severe depression.<br><br>CONCLUSIONS: Less dismissal of symptoms by healthcare providers and greater mental health support are needed, especially for racialized communities living with Long COVID. There is also a need for more employer and government financial support and for healthcare organizations to address discrimination and anti-Black racism in healthcare.},
}
@article {pmid42333348,
year = {2026},
author = {Chikkala, RKP and Garre, S and Pratyusha, AC and Ayya, SS and Sangineni, K and Gogula, S},
title = {Exploring Coagulation Abnormalities and Functional Impairment in Long COVID: Relevance to Primary Care Practice.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e109403},
pmid = {42333348},
issn = {2168-8184},
abstract = {Background The long-term sequelae of COVID-19, collectively termed long COVID, manifest as persistent symptoms that may be driven by ongoing coagulation abnormalities. Early identification, particularly in primary care, requires simple, low-cost tools that do not rely on advanced diagnostics. This study evaluated the usefulness of basic coagulation markers and the Six-Minute Walk Test (6MWT) in assessing symptom severity and functional limitation among individuals with long COVID. Methodology A two-phase observational study was conducted from July 2022 to January 2024. Phase I enrolled 197 adults more than six weeks post-COVID-19 who presented with fatigue, breathlessness, reduced exercise tolerance, cough, or musculoskeletal pain. Baseline investigations included C-reactive protein (CRP), prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, and platelet count, alongside the 6MWT. The primary objective was to evaluate the association between coagulation abnormalities and the severity of long COVID symptoms. Secondary objectives included assessment of functional impairment using the 6MWT and evaluation of persistence of coagulation abnormalities at the three-month follow-up. Patients with abnormal baseline coagulation or inflammatory parameters (n = 63) underwent repeat evaluation after three months. Results The study included 197 participants with a mean age of 37.3 ± 11.97 years, of whom 87 (44.2%) were male. Reduced effort tolerance was the most common presenting symptom, observed in 151 (76.7%) patients. At baseline, abnormalities were noted in D-dimer (50 (25.4%)), fibrinogen (43 (21.8%)), CRP (34 (17.3%)), aPTT (23 (11.7%)), PT/INR (21 (10.7%)), and platelet count (10 (5.1%)). Patients with severe symptoms demonstrated significantly higher levels of D-dimer and fibrinogen (p < 0.001 for both). Elevated D-dimer (50 (25.4%)) and fibrinogen (43 (21.8%)) were associated with an increased risk of severe symptomatology, with relative risks of 3.0 and 2.34, respectively. At the three-month follow-up, persistent elevation of D-dimer (32 (50.8%)) and fibrinogen (30 (47.6%)) was observed, indicating sustained coagulation abnormalities in a substantial subset of individuals with long COVID. Conclusions This study demonstrates a significant association between elevated D-dimer and fibrinogen levels and symptom severity in patients with long COVID. Simple, accessible tools, particularly basic coagulation tests and the 6MWT, may serve as useful adjunctive assessments for primary care physicians to identify long COVID patients with probable ongoing thrombo-inflammatory activity. Integrating these assessments into routine follow-up may improve early detection, monitoring, and targeted referral.},
}
@article {pmid42333786,
year = {2026},
author = {Habib, K and Sethi, SM and Khanum, I and Babar, R and Farooqi, H and Nasir, N},
title = {Knowledge, Attitudes, and Practices of Physicians in Pakistan Toward COVID-19 and Long COVID: A Cross-Sectional Survey.},
journal = {Asia-Pacific journal of public health},
volume = {},
number = {},
pages = {10105395261452741},
doi = {10.1177/10105395261452741},
pmid = {42333786},
issn = {1941-2479},
abstract = {Long COVID has emerged as an important post-pandemic health challenge, yet physician awareness in low- and middle-income countries remains limited. This multicenter cross-sectional study assessed the knowledge, attitudes, and practices of physicians in Pakistan regarding COVID-19 and Long COVID using an online survey conducted in 2024. A total of 117 physicians participated. While knowledge of acute COVID-19 was generally adequate, with 74.4% achieving good scores, knowledge of Long COVID was considerably lower, with only 30.8% demonstrating adequate understanding. Although most participants recognized common Long COVID symptoms (94.9%), fewer correctly identified its formal definition (37.6%). Attitudes toward COVID-19 prevention and management were largely positive (86.3%), and most participants reported appropriate clinical practices (97.4%). Female physicians had higher odds of adequate Long COVID knowledge, whereas those with more than 10 years of experience had significantly lower knowledge levels. These findings highlight a substantial gap in physician awareness of Long COVID despite strong preparedness for acute COVID-19. Targeted educational interventions are needed to improve recognition and management of post-COVID conditions, particularly in resource-limited settings.},
}
@article {pmid42336192,
year = {2026},
author = {van Bilsen, CJA and Wijnen, SMCE and Pagen, DME and Hoebe, CJPA and Dukers-Muijrers, NHTM},
title = {Workforce exit and work productivity loss in adults with and without post-COVID-19 condition: the PRIME post-COVID cohort study.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108913},
doi = {10.1016/j.ijid.2026.108913},
pmid = {42336192},
issn = {1878-3511},
abstract = {BACKGROUND: Post-COVID-19 condition (PCC) is highly prevalent, yet evidence on its long-term impact on work participation remains limited. This study assessed workforce exit and work productivity loss among adults with PCC compared to those recovered or without PCC.<br><br>METHODS: In this prospective cohort study (PRIME post-COVID) in the Netherlands, we used online questionnaire data from adults with a positive COVID-19 test between June 2020 and September 2022. Participants were categorized as PCC (not feeling recovered &#x2265;3 months post-infection), Recovered, or Never PCC. All were employed in 2022, and workforce exit, work productivity loss, work incapacity, and financial strain were evaluated in 2024.<br><br>FINDINGS: The two-year workforce exit rate was 17% in PCC (N=790), 10% in Recovered (N=437), and 9% in Never PCC (N=2,115). Rates were higher among those with PCC, older age, and health conditions. Absenteeism and presenteeism were up to three times higher in PCC and two times higher in Recovered, compared to Never PCC. Among non-employed participants, work incapacity was highest in PCC (46%) versus Recovered (17%) and Never PCC (12%). Financial strain was highest in non-employed PCC (54%) and lowest in employed Never PCC (19%).<br><br>CONCLUSION: PCC substantially impacts workforce participation and productivity. Support, interventions, and awareness are urgently needed.},
}
@article {pmid42336293,
year = {2026},
author = {Yang, Y and Kanerva, M and Liira, H and Vuokko, A and Laakso, S and Vangelova-Korpinen, V and Wang, S and Kvarnström, K and Varonen, M and Suojalehto, H and Lauerma, A and Karisola, P and Alenius, H},
title = {Integrated miRNAome-transcriptome analyses identify an immuno-hematopoietic subcluster in patients with long COVID.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2026.05.032},
pmid = {42336293},
issn = {1097-6825},
abstract = {BACKGROUND: Persistent symptoms following SARS-CoV-2 infection, termed post-COVID-19 condition or long COVID (LC), impose substantial psychological and socioeconomic burdens. However, miRNA-mRNA interactions underlying LC heterogeneity remain incompletely defined.<br><br>OBJECTIVE: To determine whether integrative blood miRNA-mRNA profiling identifies molecular LC subclusters linked to clinical and immune-hematopoietic features.<br><br>METHODS: We performed integrated miRNAome-transcriptome profiling of circulating blood RNA from individuals with LC and recovered controls. Differential miRNA and mRNA expression were assessed using LIMMA, and hierarchical clustering was used to define LC subclusters. Validated miRNA-mRNA interaction networks were constructed using miRNet. Clinical, functional, and biochemical parameters were compared between subclusters, and a random forest classifier was developed.<br><br>RESULTS: Clustering identified an immune-hematopoietic LC subcluster, LC1, characterized by extensive miRNA-mRNA dysregulation, enrichment of erythropoietic, platelet, and immune pathways, and biochemical alterations including lower plasma sodium and elevated fibrin D-dimer and thrombin time. Compared with LC2, LC1 showed persistently greater symptom burden, functional impairment, reduced quality of life, lower resilience, and higher anxiety/depressive symptoms. Potential confounding by age, sex, comorbidities, and selected medication use was evaluated. Network and co-expression analyses identified regulatory nodes enriched for viral infection and natural killer cell activation pathways. A random forest classifier incorporating nine miRNAs and LRRFIP2 achieved an AUROC of 0.91 for LC1, distinguishing LC1 from LC2 and recovered controls.<br><br>CONCLUSION: LC comprises biologically and clinically distinct subclusters shaped by coordinated miRNA-mRNA remodeling. The immune-hematopoietic LC1 subtype supports biomarker-based stratification of patients with persistent physiological and clinical impairment.},
}
@article {pmid42322759,
year = {2026},
author = {Xu, H and Du, C and Chen, Y and Liu, T and An, S and Jiang, Z and Chang, H and Su, C and Li, Q and Liang, H and Tao, H and Ru, H and Hua, T and Song, G and Sheng, J},
title = {EGCG inactivates tumor necrosis factor-alpha (TNFα) by inducing its higher-order assembly.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {159},
number = {},
pages = {158437},
doi = {10.1016/j.phymed.2026.158437},
pmid = {42322759},
issn = {1618-095X},
abstract = {BACKGROUND: Tumor necrosis factor-alpha (TNFα) is an important therapeutic target for treating a range of inflammatory and autoimmune disorders. The TNFα trimer functions by interacting with its receptors (TNFRs) on the immune cell surface and triggers downstream intracellular signaling. (-)-Epigallocatechin-3-gallate (EGCG) is the primary bioactive polyphenol compound in green tea. Our previous study found that EGCG can inhibit TNFα activity; however, the underlying molecular mechanism remains unclear.<br><br>PURPOSE: In this study, we investigated the interaction between EGCG and TNF&#x3b1; to elucidate the mechanism by which EGCG inactivates TNF&#x3b1;.<br><br>METHODS: EGCG-treated TNF&#x3b1; was analyzed using size exclusion chromatography (SEC), multiangle light scattering (MALS), and cryo-electron microscopy (cryo-EM). Mass spectrometry (MS), chemical modifications, and cell-based assays were further conducted to assess the function of the endogenous cysteines.<br><br>RESULTS: EGCG induces assembly of TNF&#x3b1; trimers into higher-order aggregation states, characterized as a non-strictly defined oligomerization. This process involves reorganization of the endogenous disulfide bond (C69-C101) through reduction and subsequent oxidation reactions. The resulting oligomers are incapable of triggering TNF&#x3b1;-TNFR signaling, and capping the free cysteines in TNF&#x3b1; abrogates the inhibitory effect of EGCG.<br><br>CONCLUSION: These findings reveal the molecular basis for the beneficial effect of EGCG in TNF&#x3b1;-associated inflammatory and autoimmune diseases, giving a new support to the consumption of regular green tea as a dietary therapy. This approach may be particularly relevant in the post-COVID-19 context for managing long COVID symptoms linked to elevated TNF&#x3b1; levels.},
}
@article {pmid42323109,
year = {2026},
author = {Mateu, L and Hansen, LL and Carmezim, JP and Loste, C and Aiello, TF and Lladós, G and Santos, JR and Pradenas, E and Trinité, B and Herrero, C and Garcia, A and Gervassi, A and Puig, T and Grau, E and Carrillo, J and Blanco, J and Kijak, GH and Tebé, C and Paredes, R and Walt, DR and Massanella, M},
title = {Blinded 2-Year Longitudinal Evaluation of SARS-CoV-2 Antigenemia in Long COVID.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2026.06.014},
pmid = {42323109},
issn = {1469-0691},
abstract = {OBJECTIVES: SARS-CoV-2 antigens have been detected in plasma months after acute infection, but their long-term dynamics and clinical relevance remain unclear. We aimed to assess the persistence and clinical specificity of plasma SARS-CoV-2 antigenemia over two years following acute infection.<br><br>METHODS: We conducted a 2-year longitudinal study involving 425 adults who developed Long COVID (n=167) or fully recovered from acute Covid-19 (n=148), and uninfected controls (n=110). Plasma samples were collected at 6-12 months and 18-24 months post-infection. SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens were quantified using the ultra-sensitive Simoa&#xae; platform blinded for clinical features. SARS-CoV-2 specific humoral responses, including neutralizing antibodies, were also assessed.<br><br>RESULTS: At 6-12 months, SARS-CoV-2 antigenemia (any antigen) was detected in 31% of individuals with Long COVID, in 20% of those fully recovered and in 5.4% of uninfected controls. By 18-24 months, positivity declined to 3%, 0% and 0%, respectively. Full spike was the most frequent antigen detected, whereas S1 was rarely observed and nucleocapsid was absent in recovered participants. Antigenemia was not associated with number or type of persistent symptoms, antibody titers, including neutralizing capacity, or vaccination status.<br><br>CONCLUSION: SARS-CoV-2 antigens circulate in plasma up to one year after infection in a minority of individuals, regardless of whether they develop Long COVID or not, and become rarely detectable later on. Therefore, current evidence does not support its use to guide clinical monitoring or treatment decisions in Long COVID.},
}
@article {pmid42325367,
year = {2025},
author = {Zhang, R and Gu, X and Zhang, H and Guo, Y and Cao, B},
title = {Long COVID: current research and future directions.},
journal = {Infectious diseases &amp; immunity},
volume = {5},
number = {4},
pages = {260-271},
pmid = {42325367},
issn = {2693-8839},
abstract = {Long coronavirus disease (COVID) is defined as the continuation or development of new symptoms three months after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and that last for at least two months, with no other explanation for their cause. This disease includes various clinical manifestations that affect multiple organ systems, such as complications in respiratory, cardiovascular, neurological, and musculoskeletal systems. The most commonly reported symptoms include fatigue, cognitive dysfunction, dyspnea, and chest pain; however, the prevalence and severity of these symptoms vary greatly among individuals. The underlying mechanisms of long COVID are complex and multifaceted, encompassing viral persistence, immune system dysfunction, mitochondrial abnormalities, endothelial impairment, and alterations in the microbiome. Further, long COVID has imposed a significant burden on individuals, healthcare systems, and the economy by impairing an individual's quality of life and functional capacity, thereby increasing costs and demand for care and rehabilitation services. This review summarizes the definition, phenotypes, mechanisms, and current treatment advancements of long COVID and highlights specific research directions for future investigation.},
}
@article {pmid42325370,
year = {2025},
author = {Liu, S and Guo, Y and Wang, FS},
title = {Viral persistence in long COVID: Research advances and treatment strategies.},
journal = {Infectious diseases &amp; immunity},
volume = {5},
number = {4},
pages = {272-288},
pmid = {42325370},
issn = {2693-8839},
abstract = {Although the coronavirus disease 2019 (COVID-19) pandemic has ended, the enduring health impacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continue to garner global attention, as approximately 10% of patients develop long COVID (post COVID-19 condition). The epidemiological characteristics and symptoms of long COVID have been reported, and various pathogenic hypotheses have been proposed. Recent evidence suggests that SARS-CoV-2 nucleic acids or fragments persist in some patients post-infection and that these are correlated with long COVID symptoms. This review focuses on clinical studies linking SARS-CoV-2 persistence to long COVID symptoms, and explores the relationship between viral persistence and other etiological hypotheses, such as immune dysregulation, vascular issues, coagulation dysfunction, microbiome dysbiosis, brainstem/vagus nerve signaling dysfunction, and latent virus reactivation. Futhermore, treatment strategies for long COVID are proposed based on current clinical trials of antiviral and immune modulation therapies. Understanding the role of viral persistence in long COVID pathogenesis is critical for developing targeted therapies and improving clinical management of this debilitating condition.},
}
@article {pmid42325555,
year = {2026},
author = {Soni, J and Ali, R and Chattopadhyay, P and Devi, P and Mehta, P and Yadav, A and Jaiswal, A and Tarai, B and Budhiraja, S and Pandey, R},
title = {Intracellular microbial shifts during COVID-19 infection and longitudinal recovery revealed by single-cell RNA sequencing.},
journal = {iScience},
volume = {29},
number = {7},
pages = {116344},
pmid = {42325555},
issn = {2589-0042},
abstract = {Host-microbe dynamics during SARS-CoV-2 Omicron variant infection and recovery remain poorly understood, particularly regarding intracellular microbial communities in immune cells. We performed single-cell RNA sequencing of 191,417 peripheral blood mononuclear cells (PBMCs) from 57 individuals (9 healthy, 24 Omicron-infected, 16 recently recovered, 8 long-recovered) using the BD Rhapsody platform. Microbial signatures identified with PathogenTrack revealed elevated alpha diversity in acutely infected and recently recovered groups, driven by opportunistic pathogens such as Escherichia coli and Providentia stuartii. In contrast, healthy and long-recovered individuals displayed commensal-dominated profiles, notably Streptomyces sviceus, indicative of restored balance. Functional analysis showed persistent microbial signatures, including Clostridium botulinum's rpoB in B cells of long-recovered individuals, broad expression of E. coli stress gene sgrR, and Mycoplasma hyopneumoniae's rpsO across 12 immune subsets. Notably, S. sviceus dnaK was exclusive to healthy monocytes. These results suggest enduring intracellular microbial influences, implicating them in long-COVID pathophysiology with potential therapeutic relevance.},
}
@article {pmid42325581,
year = {2026},
author = {Ansone, L and Pelcmane, L and Brīvība, M and Saksis, R and Silamiķelis, I and Korņejevs, K and Borisova, D and Megnis, K and Eliņa, L and Rovite, V and Vaska, A and Klavins, K and Schiöth, HB and Klovins, J},
title = {Immunothrombosis in hospitalized COVID-19 patients identified by multiomics profiling and linked to postacute complications.},
journal = {iScience},
volume = {29},
number = {7},
pages = {116326},
pmid = {42325581},
issn = {2589-0042},
abstract = {Post-acute sequelae of COVID-19 (PASC) disproportionately affect hospitalized patients and require improved molecular characterization to inform patient management. Here, we performed a prospective longitudinal multi-omics study of hospitalized COVID-19 patients, analyzing whole blood transcriptomics, targeted urine metabolomics, kidney injury biomarkers, and electronic health record-based outcome stratification across acute illness, one-month, and three-month recovery time points. Interconnected immunothrombosis-related pathways dominated the acute phase, while most immune and metabolomic pathways partially normalize. However, patients who developed long COVID exhibited a distinct blood transcriptional signature at three months consistent with an endothelial-associated activation profile, including platelet reactivity, complement dysregulation, and low-grade vascular inflammation, distinguishing them from fully recovered individuals. This multi-omics approach identifies clinically measurable biomarkers associated with longitudinal molecular trajectories and supports post-acute risk stratification.},
}
@article {pmid42325681,
year = {2026},
author = {Sheng, J and Song, Y and Zhang, A and Wang, M and Li, T and Ji, J},
title = {Unraveling the cardiovascular burden of long COVID: symptom profiles, underlying mechanisms, and clinical management insights.},
journal = {Frontiers in cardiovascular medicine},
volume = {13},
number = {},
pages = {1786633},
pmid = {42325681},
issn = {2297-055X},
abstract = {BACKGROUND: Long COVID refers to multisystem symptoms that begin within 3 months of COVID-19 infection and persist for at least 2 months. To this day, Long COVID remains a challenging clinical entity and a substantial global health burden, with cardiovascular sequelae representing a prominent component. Patients frequently report a range of symptoms including chest pain, palpitations, fatigue, and exercise intolerance.<br><br>OBJECTIVE: This mini review aims to synthesize current evidence on the symptom profiles, underlying mechanisms, and clinical management of Long COVID-related cardiovascular complications.<br><br>METHODS: We conducted a targeted narrative literature search of PubMed/MEDLINE, Web of Science, Scopus, Embase, and Google Scholar for articles published up to January 2026 using combinations of "Long COVID," "post-acute sequelae of SARS-CoV-2 infection," "cardiovascular," "myocarditis," "endothelial dysfunction," "microvascular injury," "dysautonomia," "vaccination," and "SARS-CoV-2 variants." Original studies, systematic reviews, meta-analyses, clinical guidance documents, and selected mechanistic studies were prioritized, whereas non-peer-reviewed preprints and single case reports were included only when they provided unique mechanistic or hypothesis-generating information. Eligibility was based on cardiovascular relevance to Long COVID; studies without post-acute or cardiovascular relevance were excluded.<br><br>RESULTS: The evidence indicates that cardiovascular Long COVID is heterogeneous and multifactorial, involving viral persistence, immune dysregulation, endothelial dysfunction, microvascular injury with hypercoagulability, autonomic nervous system dysregulation, and risk modification by acute disease severity, vaccination status, and SARS-CoV-2 variant period. Current management strategies remain primarily symptom-based, with emphasis on cardiovascular risk assessment, mechanism-informed phenotyping, graded rehabilitation, dysautonomia-directed treatment, and multidisciplinary follow-up.<br><br>CONCLUSIONS: Cardiovascular Long COVID is a heterogeneous burden driven by interacting mechanisms. Current evidence supports subgroup-based risk stratification and mechanism-informed management, while future studies should standardize endpoints and evaluate mechanism-targeted interventions.},
}
@article {pmid42326508,
year = {2026},
author = {Wolf, DA and Monnat, SM and Gutin, I and Wiemers, EW and Montez, JK and Deng, Q},
title = {Long COVID and Subjective Wellbeing among U.S. Working-Age Adults.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9707617/v1},
pmid = {42326508},
issn = {2693-5015},
abstract = {Background Long COVID symptoms can persist for months or years, impeding daily functioning, employment, and social relationships. While prior research links long COVID to adverse clinical mental health outcomes, less attention has been paid to broader subjective wellbeing-including life satisfaction, happiness, and hopefulness. This study examined associations between long COVID symptoms and subjective wellbeing among U.S. working-age adults, including whether associations differ by sex. Methods This cross-sectional analysis used data from the 2023 and 2024 National Wellbeing Surveys (NWS), a weighted survey of U.S. adults aged 18-64 (N = 13,990). We operationalized long COVID as having experienced any of eight symptoms (fatigue, forgetfulness, shortness of breath, joint or muscle pain, rapid heartbeat, dizziness, depression or anxiety, and exercise-exacerbated symptoms), a symptom count, and a dose-response specification. Subjective wellbeing measures include life satisfaction, happiness, and hopefulness. We estimated regression models for the full sample and separately by sex, adjusting for sociodemographic and economic characteristics. We reported results using point estimates, odds ratios (ORs) and 95% Confidence Intervals (95% CI). Results Nearly 39% (95% CI: 37.5,40.2) of respondents reported at least one long COVID symptom, with females reporting higher prevalence (43.1%) than males (34.7%) and more symptoms (mean = 1.80) than males (mean = 1.35). Long COVID was significantly associated with lower wellbeing across all three subjective wellbeing outcomes for both sexes. A dose-response pattern was observed: more symptoms were associated with progressively worse wellbeing. Among individual symptoms, depression or anxiety and cognitive difficulties exhibited the strongest negative associations with subjective wellbeing. Despite reporting higher long COVID prevalence, females had higher predicted life satisfaction and hopefulness than males at most levels of long COVID severity. Conclusions In this nationally representative sample of U.S. working-age adults, long COVID was associated with reduced subjective wellbeing across multiple operationalizations of long COVID and dimensions of wellbeing for both males and females. These findings underscore that the burden of long COVID extends beyond clinical mental health outcomes to broader evaluative and experiential dimensions of wellbeing, suggesting long COVID may represent an important population health risk for diminished quality of life.},
}
@article {pmid42326939,
year = {2026},
author = {Brewer, SE and Fisher, ME and Zittleman, L and Skenadore, A and Mullen, R and Gilchrist, E and Mallory, J and Fort, MP and Darar, M and Ahmed, FY and Warman, MK and Reno, JE and Tamez, M and Nease, DE and Kwan, BM},
title = {Health equity-oriented design for dissemination: products and impact of rapid community translation for COVID-19 vaccine promotion.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1721808},
pmid = {42326939},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/prevention &amp; control ; *Health Promotion/methods ; *COVID-19 Vaccines/administration &amp; dosage ; *Health Equity ; Colorado ; *Information Dissemination/methods ; },
abstract = {BACKGROUND: Public health messaging often falls short of the needs of underserved and minority communities, missing the mark on translating information that captures cultural, linguistic, or community relevance to influence health behaviors. Rapid community translation (rapid-CT) is an adaptation of the Boot Camp Translational method for community engagement in translating medical evidence into community health promotion messages and interventions. This paper describes the dissemination of materials from a rapid-CT of messages promoting COVID-19 vaccination among children and adults, boosters, and Long COVID messages.<br><br>METHODS: This project engaged five disproportionately impacted Colorado communities: urban and rural Latino/a/x, urban Black/African American, rural African immigrant, and urban American Indian/Alaska Native communities to conduct three cycles of about 6 week each of rapid-CT over 2021-2022. Each cycle of rapid-CT was led by 2 trained facilitators, usually one academic and one community partner. The process involved: (1) determining the role of partners and fostering partnerships; (2) describing the innovation, rationale, and evidence; (3) identifying the intended audience, message, timing, and format for dissemination; (4) selecting the communication and distribution channels; (5) identifying barriers and facilitators to dissemination, and (6) evaluating and refining the dissemination process. Dissemination was examined via tracking spreadsheet and impact was examined through surveys (recollection of seeing the materials, attitudes about COVID vaccinations, and vaccine status) and team de-briefing.<br><br>RESULTS: We engaged 126 unique community members and 15 facilitators. Within each cycle, rapid-CT communities co-created distinctive campaigns including messages, materials, and dissemination strategies. Each rapid-CT group identified anticipated and actual barriers and facilitators to the dissemination of messages and materials. Each group also demonstrated impact with metrics ranging from views of online videos or marketing materials to distributions of items promoting the message (e.g., 1,000 stickers distributed), although capacity to assess impact was a varied and the changing evidence and related to COVID-19 vaccination presented challenges.<br><br>CONCLUSION: Rapid-CT was effective for engaging communities in co-creating distinct messages and communication strategies tailored to their community's needs and populations. Rapid-CT is well-suited to message creation for dynamic public health emergencies. Future use of Rapid-CT should set clear expectations for time commitment of community partner and establish prospective evaluation plans in addition to community-developed plans.},
}
@article {pmid42327188,
year = {2026},
author = {Capistrano, KJ and Naqvi, RA and Elshourbagy, S and Class, J and Richner, JM and Etminan, S and Schwartz, JL and Li, W and Wu, CD and Naqvi, AR},
title = {Salivary microRNA Profiling of Long COVID Subjects Reveals Host-Encoded Regulators of Inflammation and Viral Persistence.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.07.730729},
pmid = {42327188},
issn = {2692-8205},
abstract = {Periodontal disease and COVID-19 are linked by convergent immunoinflammatory pathways, yet the molecular basis of their interaction remains poorly defined. Here, we present a comprehensive salivary microRNA profile from individuals with prior SARS-CoV-2 infection, sampled approximately 3-6 months after diagnosis and meeting criteria for long COVID, providing new insight into the post-viral oral microenvironment. Salivary miRNA sequencing revealed widespread repression in patients with PD, consistent with persistent immune dysregulation. Relative to COVID-19-negative/PD-negative controls, thirty-two miRNAs were differentially expressed in COVID-19-positive/PD-positive individuals, all significantly downregulated. A similar signature was observed in a post-vaccination cohort for the selected dysregulated miRNAs. Integrative pathway analyses identified these miRNAs as regulators of core inflammatory circuits, including Ras, MAPK, and NFκB signaling, converging on IL-1β- and TNF-centered networks relevant to both PD and COVID-19. Mechanistically, restoration of three downregulated miRNAs, miR- miR-30e-3p 106-3p-3p, and miR-652-3p attenuated NFκB activation and cytokine release in TLR-stimulated human oral keratinocytes, while their functional suppression using inhibitors potentiates inflammation. These miRNAs were also predicted to target SARS-CoV-2 spike and nucleocapsid transcripts, an interaction validated by dual-luciferase reporter assays. Their overexpression further reduced spike and nucleocapsid expression in Beta- and Omicron-infected epithelial cells, as measured by flow cytometry and RT-qPCR confirming host miRNAs as potent endogenous SARS-CoV-2 restriction factor. Together, these findings identify salivary host miRNAs as mechanistic regulators of oral inflammatory tone and viral persistence, establishing a molecular link between periodontal inflammation and post-COVID oral pathology.},
}
@article {pmid42328163,
year = {2026},
author = {Espín, E and Yang, C and Shannon, CP and Checkervarty, AK and Kim, S and Lapp, L and Assadian, S and Grunau, B and Goldfarb, DM and Hutton, J and Huan, T and Tebbutt, SJ},
title = {Pilot longitudinal integrated transcriptomic-metabolomic study reveals immune and metabolic signatures in non-hospitalized healthcare workers with long COVID.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1808564},
pmid = {42328163},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/metabolism ; Male ; Post-Acute COVID-19 Syndrome ; Biomarkers/blood ; Longitudinal Studies ; Metabolomics ; Female ; SARS-CoV-2 ; *Transcriptome ; Adult ; Middle Aged ; *Health Personnel ; Gene Expression Profiling ; Multiomics ; Pilot Projects ; *Metabolome ; },
abstract = {INTRODUCTION: Long COVID affects hundreds of millions of individuals worldwide, yet its underlying biological mechanisms remain incompletely understood, and the absence of validated biomarkers continues to limit diagnosis and clinical management. Most biomarker studies have focused on hospitalized patients with severe disease, leaving non-hospitalized populations, particularly healthcare workers, who are at high occupational risk, underrepresented. This gap may constrain the identification of biomarkers relevant to milder but persistent post-acute phenotypes.<br><br>METHODS: We performed integrated transcriptomic and metabolomic profiling in a longitudinal cohort of non-hospitalized healthcare workers with long COVID (N&#xa0;=&#xa0;12), primarily presenting with fatigue and brain fog, and matched controls who recovered from SARS-CoV-2 infection without sequelae (N&#xa0;=&#xa0;35). Whole-blood RNA extracted from PAXgene tubes was profiled using the NanoString nCounter PanCancer Immune Panel. Serum metabolites collected pre- and post-infection were analyzed using untargeted ultra-high-performance liquid chromatography-mass spectrometry. Differential expression and metabolite abundance were assessed using linear models with false discovery rate correction. Significant features were integrated using network- and pathway-based approaches to identify coordinated immune-metabolic alterations in long COVID.<br><br>RESULTS: Transcriptomic analysis identified 63 differentially expressed genes, including neutrophil-associated markers such as S100A8 and LY96, consistent with activation of innate inflammatory pathways. Metabolomic profiling identified 24 annotated metabolites, with oxoglutarate exhibiting a distinct longitudinal trajectory, increasing in long COVID cases while decreasing in controls. Integrated network analysis highlighted central nodes (APP, RELA, ATF2, HLA-B) and revealed pathway-level convergence on necroptosis and serotonergic synapse signaling, suggesting coordinated immune-metabolic dysregulation rather than isolated gene-level effects.<br><br>DISCUSSION: These findings generate hypotheses regarding potential links between persistent innate immune activation, metabolic reprogramming, and neurocognitive or systemic symptoms in long COVID. The observed signatures suggest immune-metabolic perturbations involving neutrophil-associated inflammatory pathways and broader cellular stress responses. However, given cohort size, platform-specific constraints, and cross-cohort heterogeneity, these signals should be interpreted at the pathway level and considered candidate mechanisms requiring validation in larger, independent cohorts of non-hospitalized individuals.},
}
@article {pmid42328235,
year = {2026},
author = {Cheng, ZS},
title = {Prioritizing long COVID related single nucleotide polymorphisms by mining genome-wide association studies of COVID-19 susceptibility and hospitalization.},
journal = {Frontiers in systems biology},
volume = {6},
number = {},
pages = {1797543},
pmid = {42328235},
issn = {2674-0702},
abstract = {Long coronavirus disease (COVID) presents a significant public health challenge, characterized by over 200 reported symptoms across multiple organ systems. Genetic studies of long COVID have been hindered by the disorder's symptom heterogeneity and the limited sample size of available datasets. To overcome these challenges, a proxy-based, hypothesis-generating strategy was conducted to prioritize candidate risk loci on studying long COVID by analyzing GWAS summary statistics of coronavirus disease 2019 (COVID-19) susceptibility, hospitalization, and long COVID from the COVID-19 Host Genetics Initiative (Release 7), resulting in 62 candidate loci represented by independent variants. These variants are grouped into three categories: (1) severe COVID-19-specific variants, exhibiting reduced signals in non-hospitalized cases; (2) variants associated with both severe and mild COVID-19, and (3) non-hospitalization-specific variants associated with mild cases. Evaluation using recently published long COVID datasets from the same consortium demonstrated that most candidate variants displayed weaker associations around nominal significance, with only a single genome-wide significant signal at rs12660421 of FOXP1. Integrative gene expression analyses further demonstrated that genes near these candidate loci exhibits weaker associations with long COVID than with acute COVID-19 outcomes. However, broader phenome-wide analyses identified 52 genes linked to traits relevant to long COVID. These candidate loci are warranted for further investigation.},
}
@article {pmid42328279,
year = {2026},
author = {Lees, CR and Morad, T and Webb, M and Sim, MS and Hsu, JJ},
title = {Long COVID sequelae in heart transplant recipients.},
journal = {JHLT open},
volume = {13},
number = {},
pages = {100600},
pmid = {42328279},
issn = {2950-1334},
abstract = {Post acute sequelae of SARS-CoV-2 infection (also known as Long COVID) have been defined as symptoms that persist after 3 months from initial acute episode of COVID-19. While the pathophysiology and mechanisms that cause Long COVID are hypothesized as secondary to persistent inflammation and immune dysregulation, the burden of this disease remains difficult to estimate due to varied symptomatology. Solid-organ transplant recipients in particular remain a vulnerable population that has been disproportionately affected by the COVID-19 pandemic, and the impact of Long COVID among orthotopic heart transplant recipients (OHTRs)-a patient population on chronic immunosuppressive therapy-remains incompletely characterized. We sought to evaluate patient-reported Long COVID symptoms between OHTRs compared to patients with baseline cardiomyopathy. We conducted a prospective survey-based study of adult OHTRs and cardiomyopathy control patients with documented SARS-CoV-2 infection. Participants completed telephone surveys, which included questionnaires of symptoms, quality of life (QOL), and mental health assessment. Between-group differences were evaluated using multivariable models adjusting for baseline characteristics. Our results show that the prevalence of Long COVID symptoms did not significantly differ between OHTRs and patients with cardiomyopathy. Dyspnea was reported more frequently in the non-OHTR group; however, this association was attenuated after adjusting for a higher burden of underlying pulmonary disease. No evidence of increased overall symptom burden was observed among OHTRs. In this first comparative analysis of Long COVID among OHTRs and control cardiomyopathy patients, OHTRs demonstrated no increase in symptom burden and may experience fewer persistent symptoms.},
}
@article {pmid42328360,
year = {2026},
author = {Wang, L and Hu, X and Yan, D},
title = {Integrative perspectives on electroacupuncture modulation of vagal-cholinergic and neuro-immune-metabolic regulation in long COVID.},
journal = {Frontiers in integrative neuroscience},
volume = {20},
number = {},
pages = {1775007},
pmid = {42328360},
issn = {1662-5145},
abstract = {Long COVID is increasingly recognized as a multisystem condition involving persistent inflammation, autonomic dysregulation, and metabolic disturbance. The vagus nerve-mediated cholinergic anti-inflammatory pathway (CAP) provides a biologically plausible link between neural regulation and immune homeostasis, while metabolic pathways involving AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) are closely related to mitochondrial function and energy balance. In this review, we synthesize evidence from neuroscience, immunology, and metabolic research to investigate how electroacupuncture (EA) may modulate vagal-cholinergic signaling and the downstream inflammatory and metabolic processes associated with long COVID. Experimental studies indicate that EA can influence CAP-related mechanisms, including α7 nicotinic acetylcholine receptor (α7nAChR)-mediated inhibition of NF-κB/NLRP3-related inflammatory signaling, and may also regulate AMPK-SIRT1-PGC-1α-associated metabolic pathways. Although clinical evidence is more indirect, it suggests that electroacupuncture may affect autonomic function, inflammatory markers, symptom burden, and neurophysiological regulation. To support a balanced interpretation, we organize the evidence in this review into a framework based on levels of evidence, which distinguishes direct preclinical findings from indirect clinical indicators and associations used to generate hypotheses. This framework highlights the potential convergence of vagal-cholinergic anti-inflammatory regulation and metabolic recovery pathways, while recognizing that several proposed connections-particularly those linking CAP-related signaling to improvements in long COVID symptoms-require further validation. Overall, this review provides a structured basis for future mechanistic studies and phenotype-oriented clinical trials evaluating EA as a neuromodulatory strategy for long COVID and related chronic inflammatory conditions.},
}
@article {pmid42328645,
year = {2026},
author = {Oka, N and Nakamura, K and Hirahata, K and Ishii, A and Yamakawa, K and Ie, K and Goto, T and Shimada, K and Fujitani, S and Kondo, K},
title = {Donepezil ameliorates fatigue and depression in PASC patients with HHV-6B SITH-1-induced acetylcholine deficiency.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1807203},
pmid = {42328645},
issn = {1663-9812},
abstract = {INTRODUCTION: The pathogenesis of post-acute sequelae of SARS-CoV-2 infection (PASC) remains poorly understood, and no effective treatment has been established. Reactivation of latent herpesviruses, particularly human herpesvirus 6B (HHV-6B), has been proposed as a possible contributor to the neuropsychiatric symptoms observed in PASC. SITH-1, a latency-associated protein expressed during HHV-6B reactivation in olfactory bulb astrocytes, induces specific antibody responses that can be detected in peripheral blood. Importantly, SITH-1 has also been identified as a risk factor for depression, suggesting a mechanistic link between HHV-6B reactivation and the development of neuropsychiatric symptoms.<br><br>METHODS: We measured serum anti-SITH-1 antibody titers in 156 PASC patients and compared them to healthy controls. In this PASC cohort, neuropsychiatric symptoms were assessed using numerical rating scales. In parallel, we developed a mouse model in which SITH-1 was transiently expressed in the olfactory bulb to assess its impact on brain function and behavior. We also conducted a subgroup analysis of a previously reported randomized clinical trial (RCT) of donepezil, stratifying PASC patients by anti-SITH-1 antibody status.<br><br>RESULTS: Anti-SITH-1 antibody positivity was observed in 62.8% of PASC patients, a significantly higher proportion than in controls. Seropositive patients exhibited more severe fatigue and depressive symptoms. In the mouse model, SITH-1 expression led to reduced acetylcholine production and depression-like behavior, both of which were ameliorated by donepezil. In the clinical trial subgroup of 73 PASC patients, 71.7% were seropositive for anti-SITH-1 antibodies. Among these individuals, donepezil significantly improved fatigue and depression scores, as measured by the Chalder Fatigue Scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS).<br><br>CONCLUSION: These findings suggest that HHV-6B reactivation in the olfactory bulb, as indicated by anti-SITH-1 antibody titers, may contribute to fatigue and depression in a subset of PASC patients. Donepezil may be effective in this subgroup, and these findings support the use of anti-SITH-1 antibody titers as a companion diagnostic marker for targeted treatment in PASC.},
}
@article {pmid42329675,
year = {2026},
author = {Axon, DR and Fenwick, S},
title = {Prevalence and Associations of Medical Expenditure Panel Survey-Defined Long COVID Among Adults: Cross-Sectional Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e92323},
doi = {10.2196/92323},
pmid = {42329675},
issn = {2561-326X},
mesh = {Humans ; Cross-Sectional Studies ; United States/epidemiology ; *COVID-19/epidemiology/economics ; Female ; Prevalence ; Post-Acute COVID-19 Syndrome ; Male ; Adult ; Middle Aged ; *Health Expenditures/statistics &amp; numerical data ; Aged ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Long COVID is a clinical condition that significantly influences quality of life, productivity, and morbidity in the individuals affected. Much of the research to date has examined medical comorbidities and their associations with long COVID, but there remains a substantial need to understand the social and behavioral factors associated with long COVID.<br><br>OBJECTIVE: The objective of this study was to investigate the prevalence and associations of Medical Expenditure Panel Survey (MEPS)-defined long COVID among adults in the United States through the application of the Andersen behavioral model.<br><br>METHODS: This cross-sectional database study used the 2022 MEPS dataset. Variables in this analysis were organized according to the Andersen behavioral model. The appropriate weighting variable was used to obtain weighted population-based estimates. Between-group differences (ie, those with MEPS-defined long COVID vs those without) were assessed using chi-square tests, and a multivariable binomial logistic regression model was developed to assess the association between each variable and having MEPS-defined long COVID.<br><br>RESULTS: A total of 11,266 individuals were eligible for inclusion in this study. This represented a weighted population of 256,500,584 American adults. Of these 11,266 individuals, 790 (7%; weighted population=18,397,214) had MEPS-defined long COVID, whereas 10,476 (93%; weighted population=238,103,371) did not. Variables identified that were statistically associated with having MEPS-defined long COVID among American adults included 3 predisposing variables (age, sex, and Asian race), 2 enabling variables (marital status and employment status), 3 need variables (number of chronic conditions, health status, and instrumental activity of daily living limitations), 1 personal health practices variable (ever receiving the COVID-19 vaccine), and 1 external environmental variable (south region).<br><br>CONCLUSIONS: The prevalence and factors associated with having MEPS-defined long COVID among American adults in this study offer insights to expand our limited understanding of the complex environmental and social factors associated with MEPS-defined long COVID. Further research is required among the long COVID population to better understand and differentiate the causes and consequences of this condition.},
}
@article {pmid42330008,
year = {2026},
author = {Chen, YH and Lin, CH and Liu, JH and Lin, HA and Hsieh, YS},
title = {Effects of incentive spirometer training on dyspnea and functional status in patients with long COVID.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0351553},
doi = {10.1371/journal.pone.0351553},
pmid = {42330008},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/complications/physiopathology/therapy ; *Dyspnea/therapy/physiopathology ; Male ; Female ; Post-Acute COVID-19 Syndrome ; Middle Aged ; *Spirometry/methods ; SARS-CoV-2/isolation &amp; purification ; Quality of Life ; Functional Status ; Aged ; Taiwan ; Adult ; *Breathing Exercises/methods ; },
abstract = {BACKGROUND: Since the emergence of Coronavirus Disease 2019 (COVID-19), it has become a global pandemic, profoundly affecting public health and daily life. Many recovering individuals report persistent or recurrent symptoms-fatigue, palpitations, cognitive impairment, shortness of breath, anxiety, and chest discomfort. These lingering effects impair work, daily function, and social interaction, placing a significant burden on individual quality of life and society.<br><br>OBJECTIVE: This study aims to evaluate the effectiveness of using an induced Incentive Spirometer as a respiratory training tool to relieve long COVID symptoms.<br><br>METHODS: This study, conducted from July 1, 2023, to May 11, 2024, at a regional teaching hospital in northern Taiwan, involved participants who had recovered from COVID-19 within the past year and had at least one long COVID respiratory symptom. Participants were assigned to one waiting control group and four experimental groups based on recovery time: within 3 months (Experimental Group 1), 3-6 months (Experimental Group 2), 6-9 months (Experimental Group 3), and 9-12 months (Experimental Group 4). The waiting control group received no interventions, while the experimental groups underwent inspiratory training using an induced Incentive Spirometer three times a week for 6 weeks (30 repetitions per session). Assessments were conducted before and after the intervention. Primary outcomes were the Dyspnoea-12 scale and Post-COVID-19 Functional Status scale. Secondary outcomes included the 6-minute walk distance and CaO&#x2082;.<br><br>RESULTS: Ninety participants were enrolled, with five withdrawing, leaving 85 for final analysis. After 6 weeks of intervention, the waiting control group showed no significant changes in dyspnea (p&#x2009;=&#x2009;0.463) or post-COVID-19 functional status (p&#x2009;=&#x2009;0.343). In contrast, all experimental groups showed significant improvements. Dyspnoea-12 scale scores improved in Experimental Groups 1 (p&#x2009;<&#x2009;0.001), 2 (p&#x2009;=&#x2009;0.008), 3 (p&#x2009;=&#x2009;0.011), and 4 (p&#x2009;=&#x2009;0.001). The Post-COVID-19 Functional Status scale also showed improvements in all Experimental Groups (Group 1: p&#x2009;<&#x2009;0.001, Group 2: p&#x2009;=&#x2009;0.003, Group 3: p&#x2009;=&#x2009;0.002, and Group 4: p&#x2009;=&#x2009;0.011). Significant improvements in 6-min walk distance were observed in some experimental groups, improvements were seen in Experimental Groups 1 (p&#x2009;<&#x2009;0.001), 2 (p&#x2009;=&#x2009;0.027), 3 (p&#x2009;=&#x2009;0.68), and 4 (p&#x2009;=&#x2009;0.172). No significant changes in CaO2 were observed (pre-test, p&#x2009;=&#x2009;0.872 and post-test, p&#x2009;=&#x2009;0.585).<br><br>CONCLUSION: Respiratory training using an induced Incentive Spirometer may help alleviate dyspnea and improve post-COVID-19 functional status in individuals with Long COVID. Earlier intervention appeared to yield better outcomes, although improvements were also observed even 9-12 months after infection. However, further studies with comprehensive pulmonary assessments are needed to confirm these findings.<br><br>CLINICAL TRIAL NUMBER: NCT06165835, registered on 9 December 2023.},
}
@article {pmid42330198,
year = {2026},
author = {Haldar, D and Rout, HS and Gupta, S and Chakraborty, S and Goel, S},
title = {Long Coronavirus Disease 2019 and its Association with Noncommunicable Diseases: A Bibliometric Analysis.},
journal = {Indian journal of public health},
volume = {},
number = {},
pages = {},
pmid = {42330198},
issn = {0019-557X},
abstract = {BACKGROUND: Long coronavirus disease 2019 (COVID-19), or post-acute sequelae of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection, has emerged as a major global health concern. Its relationship with noncommunicable diseases (NCDs) remains underexplored despite overlapping pathophysiological pathways.<br><br>OBJECTIVES: This bibliometric analysis evaluates global research trends, key contributors, and thematic clusters at the intersection of long COVID-19 and NCDs.<br><br>MATERIALS AND METHODS: A comprehensive search was conducted in Scopus and Web of Science databases using relevant MeSH and/or keyword combinations. Bibliometric indicators including publication trends, prolific authors and country collaboration networks analyzed using VOSviewer and R Bibliometrix.<br><br>RESULTS: Fifty-five relevant publications were identified between 2020 and 2024. Research activity peaked in 2023, dominated by studies on cardiovascular, metabolic, and respiratory comorbidities. Collaboration networks showed strong contributions from China, the United States, and the United Kingdom. However, limited representation was observed from low- and middle-income countries (LMICs).<br><br>CONCLUSION: This bibliometric analysis highlights a growing but uneven global research landscape linking long COVID-19 and NCDs. Cardiovascular and metabolic disorders have received significant attention, whereas neurological and oncological sequelae remain underinvestigated. Future research must strengthen interdisciplinary collaboration and address the inequitable participation of LMICs.},
}
@article {pmid42330737,
year = {2026},
author = {Vogel, JM and Jenkins, T and Cerda, M and Chen, H and Goldman, J and Katz, SD and Patterson, TF and Ashktorab, H and Bartram, L and Barua, S and Brim, H and Brown, JP and Castro, M and Chaibub Neto, E and Chestek, D and Durstenfeld, MS and Erlandson, KM and Flaherman, V and Foulkes, AS and Ghamloush, M and Haddad, F and Hadlock, J and Heath, JR and Hornikel, B and Karlson, EW and Kaufman, ES and Kellogg, DL and Levitan, EB and Levy, BD and Martin, J and McComsey, GA and Metz, TD and Motl, RW and Moukabary, T and Mullington, JM and Ofotokun, I and Okumura, MJ and Parthasarathy, S and Plunkett, BA and Reeves, WB and Rischard, F and Rizzo, J and Scott, JA and Sherif, ZA and Thaweethai, T and Trinity, JD and Tummalacherla, M and Urdaneta, AE and Vasey, AJ and Villanueva, DD and Walker, TA and Wiley, Z and Sieberts, SK and Krishnan, JA and , },
title = {Sustained Reduction in Cardiopulmonary Fitness in Long COVID: A Report from the RECOVER-adult Cohort Study.},
journal = {JACC. Advances},
volume = {5},
number = {7},
pages = {102923},
doi = {10.1016/j.jacadv.2026.102923},
pmid = {42330737},
issn = {2772-963X},
abstract = {BACKGROUND: Long-term effect of COVID-19 (Long COVID) may persist for months or years after SARS-CoV-2 infection, but longer-term cardiopulmonary manifestations have not been previously reported.<br><br>OBJECTIVES: The objective of the study was to characterize cardiopulmonary function after SARS-CoV-2 infection in a digital health substudy of the nationwide Researching COVID-19 to Enhance Recovery Adult Cohort Study.<br><br>METHODS: Associations between wearable sensor device measures of cardiopulmonary fitness and survey-derived Long COVID symptoms were estimated over a 6-month window at least 6 months after infection using linear regression models adjusted for wear time, age, sex, race/ethnicity, and body mass index.<br><br>RESULTS: Among 1,475 participants (72% female, 65% non-Hispanic White) a median of 21 months (IQR: 15-31 months) after infection, 498 (34%) had high symptom burden as characterized by the Researching COVID-19 to Enhance Recovery Long COVID Research Index (LCRI). High LCRI (vs low LCRI) was associated with significantly lower heart rate variability (-4.4 ms; 95% CI: -6.5 to -2.4; P < 0.001), higher resting heart rate (+1.5 beats/min [+0.7 to +2.4]; P < 0.001), fewer metabolic equivalent of task minutes (-96.3 [-128.8 to -63.8]; P < 0.001), lower step counts (-1,624 steps/day [-1,952 to -1,296]; P < 0.001), and lower activity levels (-7.9 minutes/day very or fairly active [-10.9 to -5.0]; P < 0.001). Hierarchal clustering analysis identified two subphenotypes with abnormal cardiovascular measures associated with low quality of life scores.<br><br>CONCLUSIONS: Long COVID is associated with worse cardiovascular fitness. Additional studies are needed to determine if Long COVID is a novel risk factor for incident cardiovascular disease.},
}
@article {pmid42321453,
year = {2026},
author = {Hooven, TA},
title = {A controlled longitudinal study clarifies the contours of pediatric long COVID.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {42321453},
issn = {1530-0447},
}
@article {pmid42321576,
year = {2026},
author = {Pence, S and Zhuang, Y and Shi, F and Yang, X},
title = {Racial Disparities and Social Determinants of Long COVID in the United States: Evidence from the 2022 Behavioral Risk Factor Surveillance System.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {42321576},
issn = {2196-8837},
abstract = {BACKGROUND: While racial disparities in COVID-19-related outcomes and the role of social determinants of health (SDOH) are well documented, few studies have examined how race/ethnicity and SDOH jointly influence the occurrence of long COVID (LC) and the variation in its primary symptoms.<br><br>METHODS: Using 2022 Behavioral Risk Factor Surveillance System data, we estimated LC prevalence across racial/ethnic groups and calculated a SDOH summary score (0-10), with higher scores indicating greater exposure to adverse SDOH. Logistic regressions were employed to assess associations of SDOH and race/ethnicity with the presence of LC and primary LC symptoms. Adjusted average marginal effects (AMEs) were calculated to quantify differences in LC prevalence across SDOH levels and racial/ethnic groups.<br><br>RESULTS: Among 92,109 respondents who tested positive for COVID-19, 20,393 (22.14%) reported experiencing LC. Compared to non-Hispanic Whites, non-Hispanic Black (adjusted odds ratio [aOR]&#x2009;=&#x2009;0.82, 95% confidence interval [CI]: 0.668-0.999) and Asian (aOR&#x2009;=&#x2009;0.58, 95% CI:0.370.89) individuals were less likely to report LC. Higher SDOH scores were associated with increased LC risk, with aOR (95%CI) being 1.47(1.28-1.69), 1.56(1.29-1.87), 2.26(1.80-2.83), and 3.21(2.65-3.89) for scores of 1, 2, 3, and &#x2265;&#x2009;4, respectively, compared with a score of 0. Compared to White individuals, Black and Hispanic respondents had higher odds of reporting joint/muscle pain (aOR&#x2009;=&#x2009;3.03, 95%CI: 1.49-6.18, and OR&#x2009;=&#x2009;3.11, 95%CI: 1.84-5.25, respectively). Higher SDOH scores were linked to increased risk of joint/muscle pain, dizziness, and post-exertional symptoms, but decreased risk of taste/smell loss.<br><br>CONCLUSION: Greater SDOH burden was associated with higher LC prevalence and variation in primary symptoms, with effects differing across racial/ethnic groups. These findings highlight the importance of addressing social conditions in efforts to reduce LC disparities.},
}
@article {pmid42313767,
year = {2026},
author = {Hirabayashi, K and Lorman, V and Wuller, S and Aragon, LV and Jhaveri, R and Jain, N and Leikauf, JE and Muszynski, JA and Martinez, AT and Higginbotham, M and Patel, PB and Sala, MA and Schulert, GS and Liu, M and Knight, S and Chrischilles, EA and Bisyuk, Y and Taylor, BW and Mosa, ASM and Gonzalez, SL and Authement, M and Bensken, WP and Fort, D and Fernandez, SA and Arnold, J and Becich, MJ and Hwang, W and Cummins, MR and Kim, S and Tedla, YG and Bailey, LC and Forrest, CB and Rao, S and , },
title = {Evaluation of steroids for acute COVID in the prevention of long COVID in children: An EHR and pediatric cohort study from the RECOVER Initiative.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0350888},
pmid = {42313767},
issn = {1932-6203},
mesh = {Humans ; Child ; Female ; Male ; Retrospective Studies ; *COVID-19/prevention &amp; control/complications ; Child, Preschool ; Adolescent ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Infant ; SARS-CoV-2/isolation &amp; purification ; *Steroids/therapeutic use ; Cohort Studies ; Electronic Health Records ; Acute Disease ; },
abstract = {BACKGROUND: Studies have shown that use of immunomodulators during the acute phase of SARS-CoV-2 infection may decrease development of post-acute sequelae of SARS-CoV-2 (PASC) or long COVID; however, such studies have not been conducted in children.<br><br>OBJECTIVE: Evaluate the effectiveness of steroid use during the acute phase of SARS-CoV-2 infection in preventing long COVID in children.<br><br>METHODS: We conducted a retrospective cohort study using target trial emulation methodology to compare children and youth who did and did not receive dexamethasone, prednisone, prednisolone or methylprednisolone within 12 days of SARS-CoV-2 infection. Inverse propensity of treatment weighting was used to balance covariates between treated and untreated patients in hospitalized and outpatient groups. The primary outcome was the development of PASC in the 1-6 months following acute infection using a computable phenotype definition. Secondary outcomes included respiratory, musculoskeletal, gastrointestinal and neurological subphenotypes and the PASC ICD-10-CM diagnosis code. We calculated hazard ratios from Cox proportional models with 95% confidence intervals.<br><br>RESULTS: From a starting cohort of 854,128 children/youth, of whom 768,845 (90.0%) were outpatients and 85,283 (10.0%) were inpatients at the time of SARS-CoV-2 infection, the weighted outpatient cohort included 22,085 steroid-treated children and 20,373 in the non-steroid group. Following weighting, the hospitalized cohort included 11,250 steroid-treated children and 10,340 untreated children. In hospitalized patients, there were no significant treatment differences in the development of PASC in the 1-6 months following acute SARS-CoV-2 infection except for a lower risk of gastrointestinal PASC in treated patients (HR: 0.58; [95% CI: 0.39-0.85], p&#x2009;=&#x2009;0.01). In outpatients, no treatment differences were observed in the development of PASC subphenotypes.<br><br>CONCLUSIONS: Steroids administered during acute SARS-CoV-2 infection did not lead to a decreased risk of PASC, with the exception of gastrointestinal presentations. Additional studies are needed to confirm the benefit of steroids and other immunomodulators in preventing long COVID.},
}
@article {pmid42314412,
year = {2026},
author = {Jokela-Pansini, M and Cousins, O and Dainow, J and Greenhough, B},
title = {From research method to community resource: Co-developing a body mapping toolkit for peer support with Long Covid patients.},
journal = {Social science &amp; medicine (1982)},
volume = {404},
number = {},
pages = {119331},
doi = {10.1016/j.socscimed.2026.119331},
pmid = {42314412},
issn = {1873-5347},
abstract = {The paper describes the development of a Body Mapping Toolkit for Long Covid Patients, co-created in collaboration with the patient-led organisation Long Covid Support. We discuss how the use of body mapping, a participatory and arts-based research method, can support a more holistic and embodied understanding of Long Covid attentive to the way illness experiences are shaped by patients' social, cultural, and economic contexts. We further demonstrate how, through collaboration with patient organisations, body mapping might be extended beyond this research application to create spaces for peer support within the Long Covid community. Toolkit redevelopment was informed by three online body mapping workshops with a total of 13 participants, two follow-up feedback workshops and a feedback survey, all conducted in 2024. Our findings demonstrate that online body mapping workshops provide a safe space and opportunity to process experiences through creativity and storytelling and an accessible and flexible way for people with particularly challenging symptoms and restrictions to discuss their experiences with others. We also reflect on some of the limitations and challenges we encountered, and how we sought to mitigate these. The article thereby: (i) contributes to current approaches in medical humanities, medical anthropology and health geography concerned with centering patient narratives of illness experience; (ii) illustrates the value co-producing knowledge and resources with patients; and (iii) offers an example of how creative methods can be drawn on as a resource for both research and peer support.},
}
@article {pmid42320154,
year = {2026},
author = {Reeves, J and Daynes, E and Janaudis-Ferreira, T and Agarwal, K and Spencer, L and Tsai, LL and Alison, JA},
title = {Physiotherapy management of Long-COVID: an evidence-based approach.},
journal = {Brazilian journal of physical therapy},
volume = {30},
number = {4},
pages = {101609},
doi = {10.1016/j.bjpt.2026.101609},
pmid = {42320154},
issn = {1809-9246},
abstract = {BACKGROUND: Long-COVID is a heterogenous, episodic, and multisystemic condition which can result following infection with a novel pathogen, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Whilst a precise pathophysiological cause is unknown, several mechanisms are hypothesised, each with plausible scientific rationale. Most people experiencing persistent symptoms following COVID-19 infection recover, yet some experience severe and debilitating illness for years after infection. Strategies to manage the sequelae of Long-COVID can improve the lives of sufferers.<br><br>OBJECTIVE: To describe the physiotherapy management of Long-COVID based on current evidence.<br><br>CONTENT: Those with 'invisible illness' (illness without outwardly visible signs), such as Long-COVID, often report stigmatisation and scepticism from healthcare systems. Validation of the experience of those with Long-COVID is therefore crucial to ensure patient-centred care. Thorough patient assessment is required to provide tailored management approaches given the diversity of Long-COVID presentations. Red flags that may contraindicate certain rehabilitation approaches (particularly exercise-based interventions) or that warrant further investigation should be considered. Assessments of fatigue, post-exertional malaise, respiratory symptoms, neurocognitive symptoms (i.e., brain fog), physical function, and orthostatic intolerance are strongly recommended. Management strategies may involve pacing and energy conservation techniques, pulmonary rehabilitation, inspiratory muscle training, dysfunctional breathing retraining, lifestyle and dietary strategies to manage orthostatic intolerance, and return-to-work planning.<br><br>CONCLUSION: Physiotherapists are well positioned to deliver individualised, patient-centred, and validating care based on best available evidence.},
}
@article {pmid42320559,
year = {2026},
author = {Thomas, N and Huang, K and Schneider-Futschik, EK and Pollack, B and Tal, MC and Fineberg, D and Wang, X and Gurvich, C and Pretorius, R and Bergquist, J and Armstrong, CW},
title = {Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research.},
journal = {Frontiers in neuroendocrinology},
volume = {},
number = {},
pages = {101268},
doi = {10.1016/j.yfrne.2026.101268},
pmid = {42320559},
issn = {1095-6808},
abstract = {Hormonal dysregulation is increasingly reported in ME/CFS and Long COVID, yet the broader role of neuroendocrine disruption in these conditions remains underexplored. While changes in steroid, peptide, and neuropeptide hormones have been identified, these findings are often considered in isolation and without attention to their timing or integration within broader physiological systems. The hypothalamic-pituitary axes regulate endocrine, immune, autonomic, nervous, and metabolic functions, systems commonly affected in both conditions, yet their circadian and menstrual dynamics are rarely investigated. In this review, we examine the evidence for neuroendocrine dysfunction in ME/CFS and Long COVID, focusing on hormone output, functional assays, receptor expression, and the coordination of endocrine biorhythms. Sex hormone signalling emerges as a key area of vulnerability, particularly given the female predominance in both conditions and the complexity of reproductive hormone regulation. We argue that accurate hormone measurement and time-structured sampling, including circadian and menstrual rhythms, are essential for detecting meaningful biological differences. By embedding chronobiology-aware, dense-sampling strategies and integrating multi-omic analyses into multi-system study designs, we outline a framework for investigating dynamic endocrine mechanisms underlying symptom variability and multisystem dysfunction, which may ultimately support the development of more targeted, personalised interventions.},
}
@article {pmid42308676,
year = {2026},
author = {Peter, N and Ramya, IS},
title = {Central sensitization in long COVID: Associations with autonomic symptom burden, cerebral hypoperfusion, and neuroinflammation.},
journal = {Journal of the neurological sciences},
volume = {488},
number = {},
pages = {126058},
doi = {10.1016/j.jns.2026.126058},
pmid = {42308676},
issn = {1878-5883},
abstract = {BACKGROUND: The mechanisms driving the broad spectrum of Long COVID symptoms-such as fatigue, brain fog, pain, and dysautonomia-remain uncertain. This study investigated central sensitization (CS) as a potential contributor to symptom burden in patients with Long COVID. We aimed to examine its association with symptom severity, as well as objective cerebrovascular, autonomic, and inflammatory markers.<br><br>METHODS: A total of 169 consecutive patients with Long COVID referred for evaluation of orthostatic intolerance underwent assessment using the Central Sensitization Inventory, symptom burden surveys (autonomic: COMPASS-31; sensory: NTSS-6; global health: PROMIS), autonomic function testing (deep breathing, the Valsalva maneuver and head-up tilt test with transcranial Doppler and capnography monitoring), and skin biopsies for small-fiber assessment.<br><br>RESULTS: CS was present in 81% of participants. Patients with CS were more often female (79.6% vs. 53.1%, p&#xa0;=&#xa0;0.004) and had higher rates of anxiety, depression, fibromyalgia and headaches, as well as a significantly greater autonomic, sensory and global health symptom burden (all p&#xa0;<&#xa0;0.001). Compared with patients without CS, they also exhibited a greater decline in orthostatic cerebral blood flow velocity (-25.53%&#xa0;&#xb1;&#xa0;11.19 vs. -22.09%&#xa0;&#xb1;&#xa0;10.53, p&#xa0;=&#xa0;0.038) and higher interleukin-6 levels (p&#xa0;=&#xa0;0.041). Autonomic failure, most commonly of mild grade, occurred at similar frequency in both groups (84.7% vs. 84.4%, p&#xa0;=&#xa0;0.999). Skin biopsies demonstrated a comparable prevalence of abnormal findings in both groups (50.8% vs. 52.0%, p&#xa0;=&#xa0;0.999).<br><br>CONCLUSION: Central sensitization appears highly prevalent among patients with Long COVID and may contribute to their multisystem symptomatology. Cerebral hypoperfusion, and neuroinflammation may constitute pathophysiological mechanisms underlying central sensitization in this population.},
}
@article {pmid42309909,
year = {2026},
author = {Guedj, E and Horowitz, T and Verger, A},
title = {Brain [18F]FDG PET in Encephalitis and Postinfectious Neurocognitive Syndromes.},
journal = {PET clinics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cpet.2026.05.003},
pmid = {42309909},
issn = {1879-9809},
abstract = {Brain [18F]FDG PET can reveal metabolic abnormalities that precede, exceed, or clarify structural MR imaging findings. Among inflammatory brain diseases, the strongest clinical rationale is currently in autoimmune encephalitis, where fluorodeoxyglucose (FDG) PET increases diagnostic sensitivity, supports syndrome-oriented metabolic pattern recognition, and may contribute to selected follow-up. In viral encephalitis, use is selective rather than routine. In post-coronavirus infectious disease (COVID) condition and related postinfectious syndromes, FDG PET may support biological stratification and differential diagnosis in a subset of patients. Interpretation remains highly dependent on clinical context and methods. Translocator protein (TSPO) PET adds mechanistic information on neuroimmune activation but belongs mainly to the research domain.},
}
@article {pmid42310705,
year = {2026},
author = {Kabir, F and Yin, KN and Jeffree, MS and Ahmedy, FB and Jahan, S and Rahman, E and Galeb, AH and Ahmed, S and Hossain, T and Ahmed, R and Hossain, MA},
title = {Effectiveness of adapted physical activity and therapeutic exercise programme in improving chronic fatigue syndrome in long COVID, delivered via hospital-based rehabilitation versus telerehabilitation.},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-026-09769-2},
pmid = {42310705},
issn = {1745-6215},
abstract = {BACKGROUND: Long COVID is a prevalent condition characterised by pain, fatigue, disability, and a multitude of health issues. There are various treatment options for managing long COVID symptoms, including non-pharmacological interventions like physiotherapy and rehabilitation, which can be effectively delivered either in institutional care settings or via telerehabilitation.<br><br>METHODS: This three-arm randomised controlled trial included 145 participants selected from a population-based cohort in eight administrative divisions in Bangladesh. Participants aged 18 and above diagnosed with chronic fatigue syndrome&#xa0;(CFS) secondary to long COVID were included and history of fatigue, cardiovascular, neuro-musculoskeletal, or respiratory diseases, or red flag signs were excluded. Participants were allocated to three groups: hospital-based rehabilitation (HBR), telerehabilitation (TR), or a home programme (HP). Interventions consisted of an individualised exercise programme. The HBR and TR groups received physiotherapist-supervised sessions with sessions lasting 45&#xa0;min, twice&#xa0;weekly for 8 weeks. And the HP group performed exercises independently following structured instruction. Fatigue, the primary outcome, was measured using the Chalder fatigue scale, while secondary outcomes were quality of life measured using the 36-item Short Form Survey (SF-36), disability-adjusted life years (DALYs), and cardiorespiratory parameters (blood pressure, pulse rate, oxygen saturation, and lung capacity).<br><br>FINDING: Between 1st July 2023 and 31st December 2023, 145 participants were enrolled, with a mean age of 46.1&#x2009;&#xb1;&#x2009;6.7&#xa0;years. After 8&#xa0;weeks of intervention, the among-group within-group comparison showed a significant difference in fatigue level (HBR: P&#x2009;<&#x2009;0.001; TR: P&#x2009;<&#x2009;0.001; HP: P&#x2009;<&#x2009;0.321), physical functioning (HBR: P&#x2009;<&#x2009;0.001; TR: P&#x2009;<&#x2009;0.001; HP: P&#x2009;<&#x2009;0.057), and episodic disability (HBR; TR; HP: P&#x2009;<&#x2009;0.001) among the participants when comparing them between the groups. In multiple comparisons, results showed that differences were observed in the Chalder fatigue scale, physical functioning, and episodic disability between all groups. Hospital-based rehabilitation showed a lower mean score compared to telerehabilitation (p&#x2009;<&#x2009;0.0001) and the home programme (p&#x2009;<&#x2009;0.0001). Additionally, telerehabilitation was significantly better than the home programme (p&#x2009;<&#x2009;0.0001), indicating hospital-based rehabilitation's superior efficacy in reducing fatigue, improving physical function, and reducing disability.<br><br>CONCLUSION: Physiotherapy as hands-on implementation in a hospital setting was substantially more effective than telerehabilitation. Training healthcare professionals to improve accessibility to rehabilitation would help mitigate the consequences of long COVID-19.<br><br>TRAIL REGISTRATION: The trial was registered with the clinical trial registry of India (CTRI/2023/03/050808. Registered on 17/03/2023).},
}
@article {pmid42302030,
year = {2026},
author = {Helmsdal, G and Kristiansen, MF and Gaard, EK and Eysturoy, BJ and Weihe, P and Eliasen, EH and Petersen, MS},
title = {Persistent symptoms, cognitive impairment, and clinical predictors of long COVID one year after Omicron infection: A clinical case-control study from the Faroe Islands.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0351564},
doi = {10.1371/journal.pone.0351564},
pmid = {42302030},
issn = {1932-6203},
mesh = {Humans ; Case-Control Studies ; Male ; Female ; *COVID-19/epidemiology/complications/diagnosis/virology ; Middle Aged ; Post-Acute COVID-19 Syndrome ; *Cognitive Dysfunction/epidemiology/etiology ; SARS-CoV-2/isolation &amp; purification ; Adult ; Aged ; Fatigue ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Six years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.<br><br>OBJECTIVES: The aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.<br><br>METHODS: We conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).<br><br>RESULTS: A total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13-1.30, p&#x2009;<&#x2009;0.001). Sub-analysis showed particularly strong associations for fatigue, cognitive impairment, neurological symptoms, and symptoms from the cardiopulmonary and musculoskeletal systems. Both mental impairment and fatigue independently predicted long COVID (aOR 1.27, 95% CI 1.14-1.42, p&#x2009;<&#x2009;0.001, and aOR 1.27, 95% CI 1.11-1.46, p&#x2009;<&#x2009;0.001, respectively). Additionally, a higher number of self-reported infections during the follow-up period increased the odds of long COVID (aOR 1.57, 95% CI 1.06-2.34, p&#x2009;=&#x2009;0.025), though this was not reflected in antibiotic use. Finally, blood analyzes showed that lower white blood cell counts were associated with increased odds of long COVID in women, but not in men, however the clinical significance of this finding remains uncertain.<br><br>CONCLUSIONS: One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.},
}
@article {pmid42302052,
year = {2026},
author = {Kim, SJ and Kim, J},
title = {Symptom profiles and health-related quality of life in Korean adults with post-acute sequelae of SARS-CoV-2 infection (PASC): A latent profile analysis.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0351506},
doi = {10.1371/journal.pone.0351506},
pmid = {42302052},
issn = {1932-6203},
mesh = {Humans ; *Quality of Life ; Republic of Korea/epidemiology ; *COVID-19/complications/epidemiology ; Adult ; Middle Aged ; Female ; Male ; Post-Acute COVID-19 Syndrome ; Symptom Burden ; SARS-CoV-2/isolation &amp; purification ; Aged ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Post-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.<br><br>OBJECTIVES: In this study, we aimed to classify the symptom profiles of Korean adults with PASC using latent profile analysis (LPA) and examine the differences in HRQoL and associated factors between the identified profiles.<br><br>METHODS: We conducted an online survey of 629 adults in Korea who experienced persistent symptoms &#x2265;12 weeks after coronavirus disease (COVID-19) diagnosis. Symptom burden was assessed using the Long COVID Symptom Tool (26 items), and HRQoL was measured using the SF-36 v2&#xae;. LPA was performed to identify the symptom subgroups. One-way analysis of variance (ANOVA) and multiple linear regression were used to compare HRQoL across profiles and explore predictors.<br><br>RESULTS: A four-class model provided the best fit: Class 1 (Low symptom, 23.3%), Class 2 (Moderate multisystem, 44.1%), Class 3 (Fatigue/post-exertional malaise dominant, 15.9%), and Class 4 (High multisystem burden, 16.7%). HRQoL differed significantly between classes (p&#x2009;<&#x2009;.001), with a clear gradient of decreasing scores from low to high symptom burden. The independent predictors of lower HRQoL included lower education, presence of chronic disease, poor subjective health, hospitalization during acute infection, and prolonged symptom persistence. The model explained 32.9% of the variance in HRQoL.<br><br>CONCLUSIONS: Korean adults with PASC exhibit heterogeneous symptom patterns that substantially affect their HRQoL. The identification of distinct symptom profiles supports the need for tailored interventions, including rehabilitation, cognitive training, and psychological support. Our findings provide crucial evidence for developing Korean population-specific screening tools and management guidelines for PASC.},
}
@article {pmid42306079,
year = {2026},
author = {Inderyas, M and Thapaliya, K and Marshall-Gradisnik, S and Barnden, L},
title = {Investigation of BOLD signal intensities in long COVID patients using 7T functional MRI.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {54},
number = {},
pages = {101266},
pmid = {42306079},
issn = {2666-3546},
abstract = {Long COVID is increasingly associated with disruption in brain homeostasis, manifesting as severe neurological dysfunction, brain fog and cognitive impairment. This present study investigated localised cognitive deficits in long COVID patients by examining brain blood oxygenation-level-dependent (BOLD) signal activity using ultra-high-field 7 T (7T) task-based functional magnetic resonance imaging (fMRI). Whole-brain BOLD signal differences were assessed across 19 long COVID patients, and 27 healthy controls (HC) including 12 COVID-recovered (Cov-RHC) and 15 COVID-19-naïve HC (nHC). 225 fMRI volumes were acquired during the Stroop colour-word task. Functional and anatomical images were processed using SPM12 to extract the BOLD signal intensity time course from whole-brain voxels for inferences between cohorts during task-fMRI. Significantly low BOLD activation in long COVID patients was observed compared to Cov-RHC in the anterior cingulate cortex (p = 0.002, cluster size=650, Z-value = 4.67), and the precuneus (p = <0.001, cluster size = 1893, Z-value = 4.67). Furthermore, BOLD intensities in precuneus showed a negative association with self-reported pain scores (p = 0.040) and the duration of illness (p = 0.03) in long COVID patients, suggesting significant correlation between BOLD signal and an increase in duration of illness and pain levels. No statistically significant BOLD differences were observed for inter-group comparisons between nHC vs. long COVID, and nHC vs. Cov-RHC. Response times to incongruent (p = 0.002) and congruent task stimuli (p = 0.001) significantly varied between nHC and long COVID cohorts, demonstrating overall faster information processing by nHC. Reduced BOLD signals to 'core' brain regions in long COVID imply reduced cognitive control by intrinsic networks that mediate information processing, cognitive and executive functions due to perturbations linked to cerebral blood flow, oxygenation status, and ongoing neuroinflammation.},
}
@article {pmid42294358,
year = {2026},
author = {Chetty, L and Reddy, P and Ramdin, S and Govender, N},
title = {Long term cardiometabolic outcomes in COVID positive patients.},
journal = {Journal of public health research},
volume = {15},
number = {2},
pages = {22799036261445801},
pmid = {42294358},
issn = {2279-9028},
abstract = {In South Africa, approximately 4.5 million confirmed COVID-19 cases and 103,000 deaths have been noted. Symptoms range from being asymptomatic, mild respiratory issues to severe multi-organ failure and consequent death. Cardiometabolic risk factors, viz., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), atherosclerosis, chronic kidney disease, hypertension, heart failure, and obesity, are flagged as the most prevalent comorbidities associated with the risk of severe COVID-19 and death. Many who have recovered from hospitalization continue to experience lingering symptoms known as long COVID, which have been linked to new-onset cardiometabolic disorders (CMD). This narrative review thus focusses on the clinical factors and the patient burden of diabetes mellitus and hypertension as two of the most commonly observed CMD, and aims to raise awareness regarding possible cardiometabolic complications. The findings expand the existing literature on the cardiometabolic effects of COVID-19, concentrating on outcomes observed more than three months after the acute phase of the illness.},
}
@article {pmid42294462,
year = {2022},
author = {Jiang, S and Loomba, J and Sharma, S and Brown, D},
title = {Vital Measurements of Hospitalized COVID-19 Patients as a Predictor of Long COVID: An EHR-based Cohort Study from the RECOVER Program in N3C.},
journal = {Proceedings. IEEE International Conference on Bioinformatics and Biomedicine},
volume = {2022},
number = {},
pages = {3023-3030},
pmid = {42294462},
issn = {2156-1125},
abstract = {It is shown that various symptoms could remain in the stage of post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as Long COVID. A number of COVID patients suffer from heterogeneous symptoms, which severely impact recovery from the pandemic. While scientists are trying to give an unambiguous definition of Long COVID, efforts in prediction of Long COVID could play an important role in understanding the characteristic of this new disease. Vital measurements (e.g. oxygen saturation, heart rate, blood pressure) could reflect body's most basic functions and are measured regularly during hospitalization, so among patients diagnosed COVID positive and hospitalized, we analyze the vital measurements of first 7 days since the hospitalization start date to study the pattern of the vital measurements and predict Long COVID with the information from vital measurements.},
}
@article {pmid42300213,
year = {2026},
author = {da Silva Almeida, I and de Jesus Ferreira, LG and Vaz, MA and Costa, RR and Babault, N and de Cássia Marqueti, R and Durigan, JLQ},
title = {Muscle fatigue in patients with severe long COVID: A 2-year follow-up study.},
journal = {PM &amp; R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70165},
pmid = {42300213},
issn = {1934-1563},
support = {001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; COFECUB88887.188974/2025-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 00193.00000773/2021-72//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193.00001222/2021-26//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193-00001261/2021-23//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193-00002357/2022-90//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193-00001623/2024-29//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 308519/2025-6//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 402816/2023-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 141130/2023-7//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 131422/2023-5//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
abstract = {BACKGROUND: Fatigue is recognized as one of the most persistent and debilitating symptoms of long COVID, affecting both functionality and quality of life. However, its long-term effects, especially beyond the first year after infection, remain poorly understood.<br><br>OBJECTIVE: To investigate self-reported fatigue and muscle fatigability in individuals with severe long COVID compared to matched healthy controls at 18 and 24 months post infection.<br><br>DESIGN: Longitudinal observational study.<br><br>SETTING: The study was conducted at the Laboratory of Muscle and Tendon Plasticity at the University of Bras&#xed;lia.<br><br>PARTICIPANTS: Twenty survivors of severe-COVID and 20 age- and gender-matched controls underwent repeat assessments at 18 and 24 months following hospital discharge.<br><br>INTERVENTIONS: Not applicable.<br><br>MAIN OUTCOME MEASURES: Perceived fatigue was measured using the Fatigue Severity Scale, functionality with the 30-second sit-to-stand test, muscular dimensions and quality assessment were evaluated through ultrasound-derived thickness and echogenicity, and muscle fatigability was assessed using torque, torque-time integral, and rate of force development. The generalized estimating equations method was used with "group" and "assessments" as factors, with the least significant difference test identifying specific differences. Chi-square test compared categorical variables.<br><br>RESULTS: The severe-COVID group showed consistently poorer functional performance (mean difference: 2.65 [0.45-4.85], p&#x2009;=&#x2009;.018), higher perceived fatigue (2.25 [1.54-2.95], p&#x2009;<&#x2009;.001) and lower rate of force development (-103.68 [-177.22 to -30.13], p&#x2009;=&#x2009;.006) compared to controls. No significant differences were observed in muscle thickness or echogenicity between groups.<br><br>CONCLUSION: Long COVID is associated with sustained fatigue, impaired neuromuscular function, and reduced physical performance up to 2&#x2009;years after infection. These findings underscore the need for long-term, mechanism-based rehabilitation strategies targeting central fatigue and neuromuscular function.<br><br>TRIAL REGISTRATION: NCT04961255.},
}
@article {pmid42301571,
year = {2026},
author = {Montgomery, A and Erdmann, N and Jinright, A and Hall, W and Burkholder, G and Johnson, R and Lund, F and Levitan, E},
title = {Mental and Physical Health Predictors of Return-to-Work Outcomes among Individuals with Long COVID Symptoms.},
journal = {International journal of behavioral medicine},
volume = {},
number = {},
pages = {},
pmid = {42301571},
issn = {1532-7558},
abstract = {BACKGROUND: Emerging evidence shows that infectious diseases, such as COVID-19, can lead to chronic health conditions. Long COVID symptoms such as fatigue, cognitive impairment, and psychological distress can significantly hinder return-to-work, complicating recovery and rehabilitation. This study explores how these persistent symptoms affect work outcomes to inform clinical and policy interventions supporting affected individuals.<br><br>METHODS: We conducted a single-site study of patients following acute SARS-CoV-2 infection (N&#x2009;=&#x2009;206, 128 employed prior to infection). Participants reported symptoms that occurred anytime between COVID-19 infection and survey completion and their work status. A classification decision tree was generated with return-to-work status as an outcome.<br><br>RESULTS: Among 128 participants, 65% (n&#x2009;=&#x2009;83) returned to their usual work duties after COVID-19 infection, with a mean recovery time of 21&#xa0;days. Twenty percent (n&#x2009;=&#x2009;25) resumed work under modified conditions (e.g., reduced hours or remote work) after a mean of 43&#xa0;days, and 10% (n&#x2009;=&#x2009;13) were unable to return due to persistent symptoms. The top five important variables that predicted work status post-COVID-19 infection were mental health, physical health, emotional distress, recovery days, and back pain.<br><br>CONCLUSIONS: Overall, global mental and physical health status are stronger predictors of return-to-work status after COVID-19 infection than most individual long COVID symptoms, with the exceptions of emotional distress and back pain symptoms. Patients who have issues with mental health, physical health, emotional distress, long recovery time, and back pain are a primary group that needs support with transitioning back to work.},
}
@article {pmid42301723,
year = {2026},
author = {Tc, HD and S, C and J, K and J, P and S, M and F, M and Tm, M and Ce, B},
title = {Post COVID REspiratory mechanisms and the efficacy of a breathing exercise intervention for DYsregulated breathing (Remedy): A feasibility RCT study.},
journal = {Chronic respiratory disease},
volume = {23},
number = {},
pages = {14799731261454679},
doi = {10.1177/14799731261454679},
pmid = {42301723},
issn = {1479-9731},
mesh = {Humans ; Feasibility Studies ; *COVID-19/complications/physiopathology ; *Breathing Exercises/methods ; Female ; Middle Aged ; *Dyspnea/physiopathology/therapy/etiology ; Male ; *Yoga ; Aged ; Adult ; SARS-CoV-2 ; Treatment Outcome ; },
abstract = {BackgroundDysregulated breathing is a major cause of persisting breathlessness for many people following acute COVID-19 illness. There is little evidence to support the use of breathing interventions within this population.MethodsA feasibility study was conducted to investigate the potential role of supervised, remote online yogic breathing as an intervention, compared to usual care. The intervention was a six-week group programme, in which they were encouraged to attend bi-weekly. Primary outcomes of attendance, completion and acceptability were recorded and a survey following the intervention. Secondary measures of breathlessness and physical function were collected.ResultsOf 122 people invited who had reported dysregulated breathing at the time of clinical consult, 40 consented and 34 were randomised (Intervention n=17, usual care n=17), 33 had initial assessment (n=16 and n=17) and with post-intervention outcomes available in n=13 and n=14, respectively. Of the 13 in the intervention arm, 5 people completed >75% of sessions and the post intervention assessment. The median number of sessions attended per participant was 7. No safety issues were recorded. The survey (n=13) of the actual intervention highlighted it was well received but there was limited options for attending. Although some breathlessness measures improved in the people receiving the intervention, there was no significant difference when comparing the intervention to usual care arms.ConclusionsThe feasibility of the study was limited in this select population of people after COVID-19 with dysregulated breathing. The intervention was well received, but attendance at all the sessions was challenged by the limited options for the sessions.},
}
@article {pmid42301972,
year = {2026},
author = {Gale, N and Beetham, H and Lyden, S and Gill, P},
title = {Community-delivered hyperbaric oxygen therapy for people affected by long COVID: a pilot study.},
journal = {British journal of nursing (Mark Allen Publishing)},
volume = {35},
number = {12},
pages = {626-632},
doi = {10.12968/bjon.2025.0241},
pmid = {42301972},
issn = {2052-2819},
mesh = {Humans ; *Hyperbaric Oxygenation ; Pilot Projects ; *COVID-19/therapy/complications/nursing ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Female ; Male ; Middle Aged ; Aged ; Fatigue/therapy/etiology ; Dyspnea/therapy/etiology ; Diving and Hyperbaric Medicine ; },
abstract = {Long COVID is an umbrella term commonly used to describe a range of symptoms, such as chronic fatigue, 'brain fog' and breathlessness, that persist for at least 12 weeks after acute COVID-19. Although there are currently no effective treatment options, emerging research indicates that hyperbaric oxygen therapy (HBOT) may help improve many major long COVID symptoms, in the short term. This mixed-methods pilot study aimed to explore the impact of HBOT, delivered in a community setting, on key long COVID symptoms. Findings indicate that fatigue, breathlessness and quality of life improved in participants who completed 4 weeks of HBOT. Although experiences of therapy were positive, with perceived improvements in significant symptoms, attending regular sessions was often difficult, due to the ongoing challenges associated with long COVID. This preliminary study suggests HBOT has potential to improve key symptoms in people with long COVID but further controlled studies are now needed.},
}
@article {pmid42302012,
year = {2026},
author = {Kehl-Floberg, K and Freisberg, E and Pop-Vicas, A and Gangnon, R and Edwards, DF},
title = {Long COVID risk by pre-infection symptoms and functional status: A retrospective cohort study of data from the All of Us Research Program.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0330793},
doi = {10.1371/journal.pone.0330793},
pmid = {42302012},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; Retrospective Studies ; Female ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Male ; Adult ; *Functional Status ; SARS-CoV-2/isolation &amp; purification ; Aged ; Risk Factors ; },
abstract = {IMPORTANCE: Over seven million U.S. adults experience persistent health issues after COVID-19, known as "long COVID". Although multiple guidelines recommend the inclusion of functional status in long COVID diagnostic criteria, more evidence is needed to guide this recommendation. This study explored the adjusted odds of developing long COVID by pre-infection symptoms and functional status, and the feasibility of estimating functional status using health records data.<br><br>DESIGN &amp; METHODS: Retrospective cohort study of U.S. adults with history of COVID-19 enrolled in a multicenter national cohort study through July 2022 (All of Us Controlled Tier CDR 7.0), using diagnostic, procedure, and billing codes from the health record, and baseline survey responses. The risk of long COVID was estimated using logistic regression by pre-infection (-5 years) incidences of (a) at least one symptom common in long COVID, and (b) functional impairment, and adjusted for disease and demographic characteristics.<br><br>RESULTS: n&#x2009;=&#x2009;65,464 met inclusion criteria; n&#x2009;=&#x2009;40,655 had post-infection occurrences of at least one symptom (long COVID group), n&#x2009;=&#x2009;24,809 had none (recovered). Adjusted odds ratios of developing long COVID increased with older age, female sex, Black racial identity, earlier variant, non-vaccination, lower pre-infection self-reported mental and cognitive health, and number of pre-infection symptoms. Adjusted odds were not significantly affected by any single pre-infection symptom, self-rated physical ability, or EHR-derived indicators of prior functional impairment.<br><br>CONCLUSIONS: In this model, there were no significant differences in risk of long COVID based on either pre-infection total incidences of long COVID symptoms (compared to the average of 4) or pre-infection functional impairment. This suggests that long COVID was associated with a change from baseline functioning and health, including in people with pre-infection incident symptoms and functional impairments. The impacts of co-occurring pre-infection symptoms requires further investigation. Both harmonized electronic health records data and patient-reported outcomes contribute important data for developing the diagnostic utility of functional status changes in long COVID.},
}
@article {pmid42286128,
year = {2026},
author = {Bird, L},
title = {Pathological potential of autoantibodies in long COVID.},
journal = {Nature reviews. Immunology},
volume = {},
number = {},
pages = {},
pmid = {42286128},
issn = {1474-1741},
}
@article {pmid42286504,
year = {2026},
author = {Xie, X and Zhao, Z and Wu, Q},
title = {Quality and reliability of short videos about long COVID on bilibili and tiktok: cross-sectional study under health community construction background in China.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-27621-9},
pmid = {42286504},
issn = {1471-2458},
support = {24CGL133//National Social Science Fund of China/ ; },
abstract = {BACKGROUND: Long COVID, characterized by persistent symptoms such as fatigue and cognitive impairment, continues to pose a global public health burden. Bilibili and TikTok are major platforms for public health information; however, the lack of systematic evaluation contributes to low-quality information and may hinder effective health management. We aimed to evaluate the quality and reliability of long COVID-related videos on these platforms.<br><br>METHODS: This cross-sectional study analyzed long COVID-related videos from Bilibili and TikTok. Inter-rater reliability was assessed using Cohen's kappa coefficient. Quality and reliability were evaluated using the Global Quality Score (GQS) and modified DISCERN (mDISCERN). Multivariate linear regression was performed to identify the independent predictors of video quality.<br><br>RESULTS: The median GQS and mDISCERN scores were both significantly higher for Bilibili than for TikTok (P&#x2009;=&#x2009;0.016 and P&#x2009;=&#x2009;0.039, respectively). Professional-source videos showed significantly higher quality than non-professional ones (P&#x2009;<&#x2009;0.001). Regression analyses revealed that a professional source was the strongest independent predictor of both GQS and mDISCERN scores (all P&#x2009;<&#x2009;0.001). Video duration and shares were significantly, albeit weakly, associated with the GQS, whereas other engagement metrics were not.<br><br>CONCLUSIONS: The overall quality of long COVID videos was suboptimal. Professional source was the primary independent predictor of higher quality, while engagement and duration showed limited influence. Strengthening platform review mechanisms and promoting evidence-based information are needed to improve public health communication.},
}
@article {pmid42287361,
year = {2026},
author = {Wu, JW and Chen, ST and Chang, FC and Chen, YL and Leung, J and Chen, MC and Lirng, JF and Chou, YH},
title = {Cerebral arteriopathy and its role in persistent post-COVID headache and brain fog: a quantitative study.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42287361},
issn = {1433-8491},
abstract = {BACKGROUND: Headache and brain fog are common after COVID-19 infection, and inflammation and vasculopathy might be the potential underlying mechanisms. This study aimed to delineate the extent and impact of cerebrovascular involvement in patients with persistent long-COVID syndrome in a large Asian cohort.<br><br>METHODS: We prospectively collected data from patients with persistent (&#x2265;&#x2009;3 months) post-COVID headache or brain fog, and controls were free from neurological symptoms within 3 months after COVID-19 resolution. The anterior and posterior Focal Cerebral Arteriopathy Severity Score (FCASS) was used to assess the severity of arteriopathy and was modified to account for bilateral involvement (total score: anterior: 0-40; posterior: 0-52). Symptom severity was assessed using monthly headache days, Migraine Disability Assessment (MIDAS), and brain fog severity scale (0-10).<br><br>RESULTS: A total of 108 patients (M: F&#x2009;=&#x2009;27:81) were divided into four groups based on symptoms categories. The presence of more symptom categories was associated with higher anterior-FCASS (combined 6.6 [2.1] vs. headache 3.6 [1.6] vs. brain-fog 4.7 [1.7] vs. control 0.8 [0.6], p&#x2009;<&#x2009;0.001 by one-way ANOVA) and a posterior-FCASS (combined 5.5 [2.2] vs. headache 4.2 [1.6] vs. brain-fog 4.4 [2.3] vs. control 0.8 [0.8], p&#x2009;<&#x2009;0.001 by one-way ANOVA). Pure brain- fog was more likely have predominance of anterior circulation involvement than pure headache (80.8% vs. 48.0%, p&#x2009;=&#x2009;0.020), but the severity of brain fog was correlated with only the posterior-FCASS (Pearson's r&#x2009;=&#x2009;0.338, p&#x2009;=&#x2009;0.009) rather than the anterior-FCASS (Pearson's r&#x2009;=&#x2009;0.173, p&#x2009;=&#x2009;0.195).<br><br>CONCLUSIONS: Anterior circulation arteriopathy and hypoperfusion may underlie persistent post-COVID brain fog. However, post-COVID headaches may not depend solely on changes in intracranial vessels.},
}
@article {pmid42287510,
year = {2026},
author = {Broughan, J and Xie, Y and Carberry, C and O'Connell, S and Fay, J and Morrison, P and Ravichandran, N and Savinelli, S and McCombe, G and Higgins, M and Lambert, JS and Cullen, W},
title = {Long covid and general practice: a survey of patients in the Republic of Ireland.},
journal = {Irish journal of medical science},
volume = {},
number = {},
pages = {},
pmid = {42287510},
issn = {1863-4362},
abstract = {BACKGROUND: Long Covid is a multi-factorial condition impacting millions globally.<br><br>AIMS: (1) To describe the demographic and health profiles of adults who have or have had Long Covid, and (2) examine their experiences of Long Covid healthcare, particularly in general practice. A cross-sectional online survey was conducted in the Republic of Ireland in April 2025.<br><br>METHODS: Survey items investigated demographics, medical history, and experiences of Long Covid care. Data was analysed using descriptive statistics and qualitative analysis of open responses.<br><br>RESULTS: Of 222 (87.05%) eligible respondents, most were 35-64&#xa0;years (n&#x2009;=&#x2009;184, 82.14%), female (n&#x2009;=&#x2009;177, 79.7%), and born in the Republic of Ireland (n&#x2009;=&#x2009;193, 86.9%). Respondents reported wide-ranging multimorbidity and Long Covid symptoms. Many strongly agreed that their symptoms were severe (n&#x2009;=&#x2009;196, 88.7%) and detrimental to quality of life (n&#x2009;=&#x2009;200, 90.1%), physical (n&#x2009;=&#x2009;202, 91%) and mental (n&#x2009;=&#x2009;98, 45%) health. Long Covid commonly lasted more than three years (n&#x2009;=&#x2009;169, 76.1%), indicating substantial long-term impact on daily functioning. Almost all consulted general practitioners for Long Covid care (n&#x2009;=&#x2009;213, 95.9%). Nearly half (n&#x2009;=&#x2009;95, 44.6%) were dissatisfied with current GP care, and many felt GPs lacked adequate knowledge of Long Covid (n&#x2009;=&#x2009;127. 59.6%). Respondents supported proposed GP-based investigative and referral interventions, as well as affirming and advocacy-focused doctor-patient relationships.<br><br>CONCLUSIONS: Continued clinical and research efforts are needed to address future Long Covid care needs. With structured, informed, holistic, and multidisciplinary care, general practice can make a positive contribution to the lives of those affected.},
}
@article {pmid42288736,
year = {2026},
author = {Perumal, N and Peine, C and Steffen, A and Wichmann, O and Harder, T},
title = {Effectiveness of seasonal mRNA COVID-19 vaccination against post COVID-19 condition between July 2023 and September 2024 among adults aged ≥ 60 years in Germany: a population-based cohort study.},
journal = {BMC infectious diseases},
volume = {26},
number = {1},
pages = {},
pmid = {42288736},
issn = {1471-2334},
mesh = {Humans ; Germany/epidemiology ; Female ; Male ; Aged ; *COVID-19/prevention &amp; control/epidemiology ; Retrospective Studies ; Middle Aged ; *COVID-19 Vaccines/administration &amp; dosage/immunology ; SARS-CoV-2/immunology ; *Vaccine Efficacy ; Seasons ; Vaccination/statistics &amp; numerical data ; Aged, 80 and over ; Cohort Studies ; },
abstract = {BACKGROUND: Some individuals infected with severe acute respiratory syndrome coronavirus 2 experience long-term symptoms, termed post COVID-19 condition (PCC). Pandemic-era studies have demonstrated moderate effectiveness of COVID-19-vaccines in preventing PCC. However, as population immunity has evolved and variant-adapted vaccines have been introduced, estimates of vaccine effectiveness and disease frequency from the post-pandemic era are needed to guide policy-making and communication.<br><br>METHODS: We investigated whether one mRNA COVID-19 vaccine dose during the 2023/2024 season was associated with reduced PCC risk in the following six months among adults aged&#x2009;&#x2265;&#x2009;60&#x2009;years in Germany. We conducted a retrospective cohort study using nationwide, outpatient claims data and performed descriptive and Poisson regression analyses.<br><br>RESULTS: In our cohort of 19,121,674 patients, 3,437,701 (18.0%) received one dose of a seasonal COVID-19 vaccine and 36,830 fulfilled the PCC case definition (incidence: 0.2%). Vaccinated individuals were older (median age 75&#x2009;years) compared to those who were not vaccinated (71&#x2009;years), with a higher proportion being female (54% vs. 46% male). 0.08% of vaccinated patients were diagnosed with PCC during study follow-up, compared to 0.22% non-vaccinated. One vaccine dose was associated with lower risk (adjusted Risk Ratio 0.37; 95% CI 0.36-0.39) of receiving a PCC diagnosis at six months post-vaccination compared to no vaccination, translating to a vaccine effectiveness of 63%.<br><br>CONCLUSION: Our results demonstrate a low PCC-incidence and a strong protective association between seasonal COVID-19 vaccination and PCC during the first post-pandemic season. These findings can help improve acceptance of COVID-19-vaccines and support doctors' and patients' decision-making regarding vaccination.},
}
@article {pmid42288901,
year = {2026},
author = {Matías-García, PR and Lai, L and Delerue, T and Ohnmacht, J and Stark, KJ and Warmerdam, R and Kolodkin, A and Six-Merker, J and Mangold, N and Günther, K and O'Sullivan, MP and Rauschenberger, A and Bohn, B and Berger, K and Fricke, J and Ahnert, P and Franke, L and Krüger, R and Gefeller, O and Überla, K and Heid, IM and Wagner, R and , and , and , and , and Waldenberger, M and Peters, A},
title = {DNAm landscape up to 4 months post SARS-CoV-2 infection: insights from four population-based cohorts.},
journal = {Clinical epigenetics},
volume = {18},
number = {1},
pages = {},
pmid = {42288901},
issn = {1868-7083},
mesh = {Humans ; *COVID-19/genetics ; *DNA Methylation/genetics ; Female ; SARS-CoV-2 ; Male ; Epigenesis, Genetic ; Middle Aged ; Cohort Studies ; Aged ; CpG Islands ; Adult ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; },
abstract = {BACKGROUND: Evidence for persistent epigenetic changes in individuals who had a mild SARS-CoV-2 infection is limited, as most DNA methylation (DNAm) studies to date have focused on either the acute phase of infection or on the months following infection in severe cases requiring hospitalization.<br><br>METHODS AND RESULTS: Using the Infinium Human MethylationEPIC BeadChip, we investigated blood DNA methylation (DNAm) up to four months after SARS-CoV-2 infection in cases and controls from four population-based cohorts (NAKO, Lifelines, CON-VINCE, and TiKoCo; n&#x2009;=&#x2009;675) within the framework of the ORCHESTRA Consortium. We observed DNAm changes at 16 differentially methylated positions (DMPs) and 21 differentially methylated regions (DMRs), with 89% of these DMPs/DMRs hypomethylated in cases compared to age- and sex-matched controls. Genes mapped to these CpGs were annotated with Gene Ontology terms and pathways related to immune responses to viral infection. eQTM analyses in whole blood from an independent cohort (KORA FF4 study) produced 49 significant CpG-transcript pairs, including IFI44L and GNA12. Despite inter-individual variability and cohort heterogeneity, our findings regarding four DMPs (IFI44L, MX1, DDX60, and RABGAP1L) and two DMRs (PARP9 and GNA12) replicate changes described both in the acute phase of infection and at long-term follow-up. Differential methylation at other novel loci may reflect the systemic nature of post-infection epigenetic changes.<br><br>CONCLUSION: Our findings suggest moderate but persistent epigenetic changes up to four months after SARS-CoV-2 infection in mild cases from population-based cohorts. These changes partially mirror those reported during the acute phase of both mild and severe COVID-19 and overlap with pathways dysregulated in autoimmune, metabolic and neurological disease. Future research should examine epigenetic changes associated with persisting symptoms in long COVID, investigate downstream effects of DNAm changes on other -omics, and consider longer follow-up periods to further elucidate the molecular mechanisms underlying SARS-CoV-2 induced epigenetic changes.},
}
@article {pmid42289828,
year = {2026},
author = {Sedgwick, TA and Ulrich, DM and Basurto, KS and Finley, JA and Boulais, BM and Ellison, RL and Warner, GA and Durkin, NM and Cerny, BM and Phillips, MS and Jennette, KJ and Pliskin, NH and Soble, JR},
title = {Performance validity test failure rates among neuropsychological outpatients clinically referred for persistent Long COVID cognitive symptoms following mild SARS-CoV-2 disease severity.},
journal = {Journal of clinical and experimental neuropsychology},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/13803395.2026.2688956},
pmid = {42289828},
issn = {1744-411X},
abstract = {OBJECTIVE: Persisting cognitive symptoms following SARS-CoV-2 infection (Long COVID) has become an increasingly common referral for neuropsychological evaluation. This study examined performance validity test (PVT) failure rates among adults referred for evaluation due to Long COVID cognitive complaints after mild SARS-CoV-2 disease severity.<br><br>METHOD: Data from 57 demographically diverse outpatients (72% female; Mage&#x2009;=&#x2009;44.23; Meducation&#x2009;=&#x2009;15.39&#x2009;years) consecutively referred for a focused neuropsychological evaluation due to Long COVID cognitive symptoms were analyzed. The neuropsychological test battery included one freestanding (Test of Memory Malingering-Trial 1) and four embedded PVTs (Reliable Digit Span; California Verbal Learning Test-Brief Form Forced Choice; Brief Visuospatial Memory Test-Revised Recognition Discriminability; Stroop Color and Word Test-Word Reading T-Score), as well as a 11 neuropsychological test scores assessing the major domains of cognition, which were used to compute an overall neuropsychological test battery mean composite score.<br><br>RESULTS: Individual PVT failure rates ranged from 4% to 18%. Overall, 67% passed all PVTs, 24% failed one PVT, and 9% failed&#x2009;&#x2265;&#x2009;2 PVTs. Patients failing two or more PVTs had an overall neuropsychological test battery mean performance that was significantly lower than the group failing one or zero PVTs and 1.0 standard deviations below the population mean. Patients with zero PVT failures also outperformed those with one PVT failure by 0.5 standard deviations. Nonsignificant differences in COVID disease characteristics emerged between groups.<br><br>CONCLUSIONS: The majority of patients (67%) passed all PVTs, with 24% of patients failing one PVT and 9% failing&#x2009;&#x2265;&#x2009;2 PVTs. Future research is warranted to understand implications of a single freestanding PVT failure in this population, and to establish base rates of invalidity in Long COVID and among those with more severe initial COVID infection necessitating hospitalization and/or medical intervention. Such practices ensure accurate diagnosis, guide treatment, and improve the reliability of research on the cognitive sequelae of COVID-19.},
}
@article {pmid42291037,
year = {2026},
author = {Seboka, BT and Ma, L and Magliano, DJ and Talic, S and Junior, ADSM and Borlotti, A and Brears, HT and Dennis, A and Banerjee, A and Marwick, TH and Huynh, Q},
title = {The impact of post-acute sequelae of COVID-19 on cardiac function and structure: A systematic review and a hybrid individual participant data meta-analysis.},
journal = {American journal of preventive cardiology},
volume = {27},
number = {},
pages = {101457},
pmid = {42291037},
issn = {2666-6677},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as Long COVID, affect a significant proportion of COVID-19 survivors, with evidence suggesting cardiovascular involvement. However, the nature, extent, and clinical significance of these alterations remain uncertain.<br><br>AIM: To synthesize evidence on structural and functional cardiac alterations in individuals with PASC compared with those without PASC.<br><br>METHOD: We systematically searched seven databases. Random-effects meta-analyses were performed and supplemented by individual participant data (IPD) analyses from three studies. Univariable and multivariable meta-regressions examined associations with study-level characteristics. Publication bias and evidence certainty were assessed using standard methods (funnel plots, Egger's test, trim-and-fill, and GRADE).<br><br>RESULTS: From 3580 records, 17 studies with 4852 participants (3173 PASC, 1679 controls) met the inclusion criteria. IPD analysis revealed an impairment in global longitudinal strain (GLS) (mean difference (MD) = 3.63 %) in individuals with PASC. When using categorical thresholds, 58 % of individuals with PASC had GLS < 16 %, indicating a significant prevalence of subclinical left ventricular dysfunction. Meta-analysis supported these findings, showing impaired GLS (MD = 1.07 %), along with reductions in left ventricular ejection fraction (MD = -1.30 %) and left ventricular end-diastolic volume (MD=-3.98 mL). Meta-regression showed that cardiac dysfunction was more frequently observed in individuals with older age, diabetes, and hypertension.<br><br>CONCLUSION: This review indicates that PASC is associated with modest, subclinical alterations in cardiac function. These alterations appear more pronounced in older adults and those with cardiometabolic comorbidities, highlighting the potential value of risk-stratified cardiovascular surveillance in individuals with PASC. The long-term clinical relevance of these changes remains unclear and warrants further study.},
}
@article {pmid42291861,
year = {2026},
author = {Elbaroumi, O},
title = {Approach to Fatigue in Primary Care: A Practical Diagnostic Framework for General Practitioners.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e108764},
pmid = {42291861},
issn = {2168-8184},
abstract = {Fatigue is one of the most common presenting complaints in primary care and poses a significant diagnostic challenge due to its multifactorial aetiology. While the majority of cases are benign and self-limiting, fatigue may also represent an early manifestation of serious underlying pathology. This review distinguishes between acute fatigue, typically transient and associated with intercurrent illness or lifestyle factors, and chronic fatigue, defined as fatigue persisting for six or more weeks, which is more likely to be multifactorial in origin. This narrative review aims to provide a practical and structured diagnostic framework for general practitioners to evaluate and manage fatigue effectively in the primary care setting. A narrative review of the literature was conducted using PubMed and Google Scholar. Searches were limited to articles published in English from 2010 onwards. Search terms included "fatigue," "primary care," "chronic fatigue," "myalgic encephalomyelitis," "post-viral fatigue," "sleep disorders," and "functional somatic syndromes." Seminal references predating 2010 were retained where no suitable replacement was available. This review did not employ a formal systematic search strategy, and no risk-of-bias assessment was performed, consistent with the narrative review format. Fatigue arises from a wide range of physical, psychological, and lifestyle-related causes, best understood through a three-tier classification: primary/idiopathic, secondary, and psychosocial. A systematic approach incorporating thorough history-taking, focused clinical examination, and judicious use of investigations is essential. Identification of red flag symptoms is critical to exclude serious conditions, including malignancy and chronic infections. A structured, patient-centred approach enables general practitioners to manage fatigue effectively while minimising unnecessary investigations and ensuring timely identification of serious disease.},
}
@article {pmid42292174,
year = {2026},
author = {Groysman, R},
title = {Long COVID as a network disorder: a mechanism-anchored framework for biological stratification and therapeutic targeting.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1841690},
pmid = {42292174},
issn = {2296-858X},
abstract = {Long COVID is increasingly recognized as a biologically heterogeneous, multisystem condition with wide variability in symptom expression and treatment response. Although symptom-based phenotyping has advanced descriptive and epidemiologic understanding, similarity in clinical presentation does not necessarily imply shared upstream pathophysiology. Therapeutic cohorts defined solely by symptom clusters may therefore combine biologically distinct mechanisms, potentially diluting treatment effects and complicating interpretation of interventional trials. This manuscript proposes a complementary, mechanism-anchored framework centered on recurrent and biologically measurable domains: autonomic dysfunction, mitochondrial and bioenergetic impairment, endothelial and microvascular dysfunction, gut dysbiosis and barrier disruption, mast cell-mediated signaling, and neuroendocrine dysregulation. These primary domains are conceptualized as physiologically coherent systems capable of generating multisystem symptom patterns in biologically enriched subsets. Secondary amplifying processes, including persistent immune activation, viral antigen persistence without established replication, autoantibody formation, neuroinflammation, and sleep-related destabilization, are positioned as network-coupling processes that may sustain or amplify dysregulation across domains. Within a network-based framework, Long COVID is conceptualized as a network disorder in which interacting regulatory nodes are hypothesized to generate self-reinforcing feedback loops that maintain symptom persistence even after resolution of acute infection. The model accommodates heterogeneity across mechanisms and alternative explanatory hypotheses. It provides an operational structure for organizing mechanistic heterogeneity and generating testable predictions. A prototype, unvalidated screening instrument is included to illustrate a potential pathway toward mechanism-informed stratification and prospective trial enrichment. Future research should evaluate whether biologically enriched cohorts demonstrate differential therapeutic responsiveness compared with symptom-defined populations. Prospective validation using standardized physiological metrics will be essential to determine whether mechanism-guided stratification improves translational precision and clarifies actionable pathophysiology in Long COVID.},
}
@article {pmid42294006,
year = {2026},
author = {Chowdhury, MMH and Fontaine, MN and Lord, SE and Lucier, JF and Allard-Chamard, H and Ilangumaran, S and Piché, A and Dionne, IJ and Ramanathan, S},
title = {Aptamer-based analyses of plasma proteome in individuals with post-COVID condition who underwent tailored physical activity.},
journal = {Frontiers in sports and active living},
volume = {8},
number = {},
pages = {1797346},
pmid = {42294006},
issn = {2624-9367},
abstract = {INTRODUCTION: Post-COVID condition (PCC) encompasses a spectrum of clinical symptoms affecting multiple organs that persist for >3 months after resolution of the initial SARS-CoV-2 infection. The complex nature of PCC symptoms makes it difficult to decipher the mechanistic basis of disease and establish efficient pharmacological interventions. However, non-pharmacological approaches such as personalized physical exercise regimen has been shown to improve the quality of life in PCC patients. Among the non-pharmacological interventions for PCC, physical rehabilitation, especially symptom-titrated physical exercise, has shown promise in restoring the quality of life but the underlying mechanisms are not yet elucidated. This personalized approach adjusts the physical training intensity according to patient's ability and tolerance levels.<br><br>METHODS: We had observed that individuals with PCC showed significant improvement following tailored physical exercise. Here the plasma samples obtained before and after the intervention was analyzed for a preselected panel of 1500 markers by SomaScan assay.<br><br>RESULTS: Proteins differentially expressed between the exercise and no-exercise groups suggest that the tailored exercise training drives distinct proteomic signatures involved in immune, vascular and oxidative stress pathways.<br><br>DISCUSSION: Despite the low sample numbers, our results indicate that the tailored exercise regimen resulted in significant alterations in biological pathways associated with PCC.},
}
@article {pmid42285845,
year = {2026},
author = {Chen, PC and Hsu, YL and Wu, LS and Liu, XL and Tsai, HJ and Wang, JY and , },
title = {Pediatric post-acute sequelae of SARS-CoV-2 infection in Taiwan: Insights from the DISCOVER cohort.},
journal = {Pediatrics and neonatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pedneo.2026.03.007},
pmid = {42285845},
issn = {2212-1692},
abstract = {The post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID, represent a multifaceted challenge in pediatric populations, characterized by symptoms persisting beyond the acute phase. In Taiwan, where early public health measures initially contained the pandemic, the 2022 Omicron surge prompted focused investigation into pediatric PASC, highlighting the critical need for longitudinal data in this specific demographic. To address this challenge, the Diagnosis and Support for COVID Children to Enhance Recovery (DISCOVER) study was established as a prospective, multidisciplinary cohort. By employing a multimodal approach, this study characterizes the clinical landscape of pediatric PASC in Taiwan through validated screening instruments, AI-driven diagnostics, and pulmonary assessments, while concurrently evaluating immune biomarkers, vaccination protection, and vitamin D intervention. This review synthesizes comprehensive findings from the cohort. While the acute phase of infection was predominantly mild, a substantial proportion of children experienced persistent multisystem symptoms, with fatigue, respiratory issues, and somatic complaints being most prevalent. Vaccination was found to significantly modify the disease trajectory, offering protection against subsequent gastrointestinal sequelae and preserving pulmonary function by mitigating small airway resistance. Furthermore, advanced diagnostic modalities, including impulse oscillometry and deep learning-assisted echocardiography, successfully unmasked subclinical organ dysfunction that conventional methods often failed to detect. Mechanistic investigations revealed that symptom severity was closely linked to elevated anti-nucleocapsid antibody titers, while markers of T-cell exhaustion evidenced persistent immune dysregulation, rather than ongoing viral replication. Notably, a preliminary single-center randomized controlled trial within this cohort provided early evidence that vitamin D supplementation may reduce the overall symptom burden and modulate pro-inflammatory cytokine profiles in children with PASC. Collectively, these findings underscore the multisystem nature and immune-driven mechanism of pediatric PASC, while highlighting the role of vaccination, advanced diagnostics, and targeted nutritional interventions in improving recovery. CLINICAL TRIAL REGISTRATION: NCT05426291 (ClinicalTrials.gov).},
}
@article {pmid42271537,
year = {2026},
author = {Skipper, L and Faghy, MA and Thomas, C and , and Ashton, REM and Bewick, T and Owen, R},
title = {Patient and public involvement and engagement in Long COVID research: embedding inclusion in research.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {},
pmid = {42271537},
issn = {2056-7529},
abstract = {BACKGROUND: Patient and public involvement and engagement (PPIE) is increasingly recognised as essential to ensuring that research is safe, inclusive and equitable, yet implementation often remains tokenistic or absent. In the ERASE-LC Trial, patients contribute as collaborators throughout the research process, helping to shape research questions, study design and delivery through their lived experience.<br><br>DISCUSSION: This paper provides examples that illustrate how lived experience can be integrated across the research lifecycle, from defining roles and responsibilities to enabling meaningful collaboration. Embedding PPIE within Long COVID research has informed approaches to engagement, accessibility, and participant safety. Although developed in the context of Long COVID, these approaches may be applicable to research in other chronic conditions and wider clinical research settings.<br><br>CONCLUSION: Drawing on reflections from our PPIE network and a case study from the Long COVID study, the ERASE-LC trial, we illustrate how inclusive and community-representative PPIE can be embedded in practice. These experiences highlight the value of flexible and accessible engagement approaches to inform co-produced recommendations for strengthening PPIE in health research.<br><br>CLINICAL TRIAL NUMBER: ClinicalTrials.gov, NCT05911906, 20/06/2023.},
}
@article {pmid42274123,
year = {2026},
author = {Saleem, S and Hussain, A and Haroon, M and Raza, A and Afzal, U and Anwar, MF and Imran, S and Iqbal, MU and Hajj, F},
title = {Dynamic microclot profiling: thromboelastography advances precision management in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Blood coagulation &amp; fibrinolysis : an international journal in haemostasis and thrombosis},
volume = {},
number = {},
pages = {},
doi = {10.1097/MBC.0000000000001439},
pmid = {42274123},
issn = {1473-5733},
abstract = {Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share overlapping symptoms, and emerging evidence implicates persistent fibrinoid microclots in their pathophysiology, contributing to impaired microcirculation. This review explores the role of microclots and evaluates thromboelastography (TEG) as a potential diagnostic tool. A comprehensive literature review was conducted using major biomedical databases. Studies indicate microclots are prevalent in both conditions. Long COVID patients demonstrate a TEG profile of increased clot strength (maximum amplitude) and reduced fibrinolysis (LY30), suggesting a persistent hypercoagulable state. Despite its advantages in real-time assessment, TEG interpretation faces challenges from preanalytical variability and a lack of standardized protocols. Promising therapeutic trials, including anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase), require further validation. Technological advancements like AI-driven TEG analysis and portable devices could improve diagnostic precision. In conclusion, persistent microclots are a key pathophysiological feature. TEG provides a promising, novel approach for detecting coagulation abnormalities and could guide treatment, but requires standardization in future clinical trials. Future research should integrate multiomics biomarkers for precision therapeutics to improve patient outcomes.},
}
@article {pmid42278658,
year = {2026},
author = {Mitkowski, P and Leśniak, M and Kobza, D and Aleksandrowicz, K and Chodowiec, A and Piwowarek, K and Włodarczyk, W and Porębska, K and Plewka-Barcik, K and Borkowska, A and Rożyńska, R and Pietruszka-Wałęka, E and Wojtyszek, A and Jahnz-Różyk, K and Pękalski, M and Chciałowski, A and Zdanowski, R and Kłos, K},
title = {Immune Dysregulation After COVID-19: Longitudinal Analysis up to 9 Months.},
journal = {International journal of molecular sciences},
volume = {27},
number = {11},
pages = {},
doi = {10.3390/ijms27115137},
pmid = {42278658},
issn = {1422-0067},
support = {DOBBIO&#x2011;12&#x2011;04&#x2011;001&#x2011;2022//National Centre for Research and Development/ ; Specialist Hospitals/43/2020//National Centre for Research and Development/ ; },
mesh = {Humans ; *COVID-19/immunology/blood ; *Cytokines/blood ; Longitudinal Studies ; Female ; Male ; Middle Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/immunology ; Aged ; },
abstract = {SARS-CoV-2 infection triggers a strong inflammatory response, and persistent symptoms after recovery are thought to reflect prolonged systemic dysregulation. However, mechanisms underlying long COVID remain unclear. This study evaluated longitudinal changes in cytokine hematological and biochemical parameters up to nine months after hospitalization for COVID-19 and examined their relationship with persistent symptoms, vaccination status, and the occurrence of comorbidities. Long COVID patients showed sustained elevations in IL-2, IL-6, IL-10, IL-17A, CXCL9, TNF-α, and IFN-γ compared with healthy controls, exhibiting heterogeneous temporal trajectories. Specifically, levels of IL-2, IL-10, TNF-α, and creatinine continued to increase over time, whereas IFN-γ, LDH, CCL2, CXCL9, and CXCL10 declined. Other parameters exhibited greater variability without a uniform longitudinal pattern. IL-6 demonstrated consistently high diagnostic performance in distinguishing individuals after COVID-19 from healthy controls (AUC > 0.82). Aging substantially affects cytokine profiles and systemic inflammatory status; therefore, residual age-related confounding cannot be fully excluded despite statistical adjustment. Although symptoms such as fatigue, cough, and dyspnea were still reported at nine months, no stable associations were identified between cytokine concentrations and clinical manifestations. These findings indicate that while immune alterations persist long after acute infection, systemic cytokine measurements alone may be insufficient to explain the presence or persistence of symptoms. The results suggest that long COVID reflects multifactorial processes extending beyond systemic inflammation and highlight the need for further research into mechanisms driving long-term long COVID sequelae.},
}
@article {pmid42278987,
year = {2026},
author = {Singer, K and Struhal, W and Rabady, S},
title = {Healthcare Pathways of Patients with Long COVID in Austria: A Qualitative Exploration of Experiences, Barriers, and Needs.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114125},
pmid = {42278987},
issn = {2077-0383},
support = {Article Processing Charge (APC)//Karl Landsteiner University of Health Sciences/ ; },
abstract = {Background/Objectives: Long COVID is characterized by persistent symptoms following SARS-CoV-2 infection and places a considerable burden on patients and healthcare systems due to its complex, multisystemic nature. In Austria, little is known about how affected individuals navigate existing healthcare structures and where obstacles occur. This study aimed to explore healthcare pathways, perceived barriers, and needs among people living with long COVID in Lower Austria. Methods: An exploratory qualitative study was conducted using semi-structured interviews with eleven adults residing in Lower Austria who reported symptoms persisting for at least four months after COVID-19 infection and still present at interview. Participants were recruited from a rehabilitation center, a neurology department, and an online patient group. Interviews were audio-recorded, transcribed verbatim, pseudonymized, and analyzed by the first author using inductive qualitative content analysis following Mayring, supported by MAXQDA 2024 software. Results: On average, each participant consulted five medical points of care and seven healthcare professionals. Approximately half utilized Austria's private healthcare sector in addition to the public one. Key barriers included fragmented care coordination, long waiting times, lack of specialist availability, financial burden, and insufficient recognition of symptoms by healthcare providers. Rehabilitation services were widely perceived as beneficial. Conclusions: Care experiences of the interviewed individuals with long COVID in Austria frequently deviate from national guideline recommendations. Although findings cannot be generalized beyond this exploratory sample, they suggest that enhancing general practitioner (GP) training, reinforcing care coordination, and broadening access to specialized interdisciplinary centers may improve equity and quality of long COVID care.},
}
@article {pmid42279051,
year = {2026},
author = {Renaudineau, Y and Teillaud, S and Chaves, SA and Alvarez, M and Barthes, R and Bost, C and Fortenfant, F and Puissant-Lubrano, B and Abravanel, F and Vellas, C and Pavy-Le Traon, A and Sailler, L},
title = {Clinical and Immunovirological Characteristics Associated with Cardiovascular Dysautonomia in Long COVID.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114192},
pmid = {42279051},
issn = {2077-0383},
abstract = {Background/Objectives: This report is an assessment of the characteristics associated with cardiovascular dysautonomia (CVD) in the context of long Coronavirus disease (COVID), which is currently inadequately characterized. Material and Methods: A retrospective cross-sectional study was performed involving 106 patients with long COVID, including 34 individuals diagnosed with CVD, among whom eight met the criteria for Postural Tachycardia Syndrome (PoTS). The variables assessed encompassed individual characteristics (e.g., age, sex, comorbidities), immunization parameters (e.g., vaccination/viral status, timing, frequency), cellular and humoral anti-Spike and anti-Nucleocapsid (Nuc) immune responses, inflammatory and allergic biomarkers, as well as an extensive panel of common autoantibodies comprising anti-nuclear antibodies, anti-central nervous system antibodies (cerebellum, brain), and anti-peripheral nervous system antibodies (gangliosides). Results: An age < 45 years, body mass index, hyperventilation syndrome as well as a higher cumulative number of antigenic contacts (vaccinations plus infections ≥ 3) and an elevated basophil count (≥0.06 G/L) were independently associated with CVD. There was no association between CVD and inflammatory markers or common autoantibodies. Patients with PoTS criteria had a strong anti-Spike cellular immune response and increased IgG anti-Nuc humoral immunity when compared with CVD and non-CVD long COVID counterparts. Conclusions: Compared to other long COVID patients, patients with long COVID-associated CVD have distinctive clinical and immunovirological features. Our results suggest the potential role of the immune response against Spike and of allergic pathways rather than humoral autoimmunity against common autoantibodies in long COVID CVD.},
}
@article {pmid42279108,
year = {2026},
author = {Balan, A and Graham, G and Herban, S and Marcu, M and Gheorghe, N and Mara, G and Rasinar, FC and Lascu, A and Mot, CI and Dan, TF and Mihaicuta, S and Frent, SM},
title = {Transcutaneous Auricular Vagus Nerve Stimulation for Post-COVID-19 Condition: A Systematic Review and Critical Appraisal of Clinical Evidence.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114247},
pmid = {42279108},
issn = {2077-0383},
abstract = {Background: Long COVID, or post-COVID-19 condition (PCC), affects around 36% of individuals following SARS-CoV-2 infection, manifesting as persistent fatigue, cognitive dysfunction, and dysautonomia among its hallmark features. Affecting an estimated 400 million individuals globally, it imposes an annual economic burden exceeding $1 trillion, yet no pharmacological therapy has demonstrated consistent efficacy in adequately powered randomized controlled trials. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a candidate intervention targeting the autonomic dysfunction and neuroinflammation responsible for PCC pathophysiology. Methods: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420261287286) searching PubMed, Scopus, Cochrane, and Web of Science databases from inception to January 2026 for studies evaluating any form of VNS in adults with Long COVID. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, the JADAD scale, and the PEDro scale. Certainty of evidence was evaluated using the GRADE framework. Narrative synthesis followed SWiM guidelines. Results: Five studies (n = 154 participants) (three randomized controlled trials (RCTs) and two single-arm studies) met inclusion criteria. Three of five studies (60%) were rated high overall risk of bias; only two RCTs achieved "some concerns." The only adequately double-blinded RCT found no significant between-group differences across all outcomes. Paradoxically, in the best-powered RCT (Percin et al.), sham stimulation produced significantly greater fatigue improvement than active taVNS, despite active taVNS producing significant HRV increases consistent with cardiac autonomic modulation. All efficacy outcomes were rated "very low" certainty (GRADE); safety was rated "low" certainty. Conclusions: Currently available evidence supporting the use of taVNS for Long COVID remains limited, and the absence of reliable target engagement markers in the included studies constrains confidence in this approach. Nonetheless, the physiological rationale remains sound, and the favorable safety profile across all included studies supports the feasibility of future investigation. However, given that positive findings were confined to inadequately controlled studies, enthusiasm for further research should be directed first toward mechanistic clarification and rigorous dose-finding work. Large-scale, double-blind, sham-controlled trials incorporating validated markers of vagal engagement are required before taVNS can be firmly recommended for COVID-19 sequelae management.},
}
@article {pmid42282195,
year = {2026},
author = {Friedly, J and Bateman, L and Berdan, LG and Casaburi, R and Erdmann, N and Felker, GM and Itchon-Ramos, N and Keteyian, SJ and MacIntyre, N and O'Brien, L and Reist, C and Rossiter, HB and Silverstein, A and Taylor, E and Pike Welch, H and Yanez, ND and Zimmerman, KO and Make, B},
title = {Rationale and Design of RECOVER-ENERGIZE: A Platform Clinical Trial of Interventions for Exercise Intolerance With and Without Post-exertional Malaise in Long COVID.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.02.26354455},
pmid = {42282195},
abstract = {INTRODUCTION: A prominent symptom of post-acute sequelae of SARS-CoV-2 infection (i.e., Long COVID) is exercise intolerance with or without post-exertional malaise (PEM). PEM is characterized by the worsening of both symptoms and function following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. Individualized, supervised cardiopulmonary rehabilitation is considered a safe and effective intervention for many cardiac and pulmonary conditions, and has been effective in gradually improving function in previously hospitalized and nonhospitalized patients with severe COVID-19. While traditional cardiopulmonary rehabilitation approaches appear helpful in some situations, the exercise intolerance symptoms experienced by many individuals with Long COVID may require a different approach, especially when attempts to increase physical activity result in PEM. No clear consensus exists on the optimal treatment of PEM, and no major studies have evaluated the efficacy in individuals with Long COVID of either carefully supervised, individualized cardiopulmonary rehabilitation programs for exercise intolerance without significant PEM or activity pacing interventions designed to treat or prevent PEM.<br><br>METHODS AND ANALYSIS: The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative funded by the National Institutes of Health (NIH) included a prospective, multicenter, randomized controlled platform trial (RECOVER-ENERGIZE) designed to assess two interventions in patients with Long COVID and exercise intolerance: (1) cardiopulmonary rehabilitation for patients without significant PEM and (2) structured activity pacing to prevent or reduce PEM in participants who experience the symptom. The intervention duration will be 12 weeks. The primary endpoints for the trial include the Endurance Shuttle Walk Test as a measure of endurance capacity for the cardiopulmonary rehabilitation intervention and a modified version of the DePaul Symptom Questionnaire-Post-Exertional Malaise for the pacing intervention. Assessments will be completed at baseline, middle of intervention, end of intervention, and 12 weeks after completion of the intervention, and include physical performance measures and patient-reported surveys.<br><br>ETHICS AND DISSEMINATION: The RECOVER-ENERGIZE trial protocol has been approved by an institutional review board (Advarra), and written informed consent will be obtained from all participants prior to enrollment. The trial is registered on ClinicalTrials.gov (NCT06404047). Formally assessing PEM and developing a structured activity pacing intervention delivered by local pacing coaches are novel features of this trial. Results will be disseminated through peer-reviewed publications, presentations at scientific conferences, and communication with participants, patient advocacy organizations, and the broader Long COVID community. De-identified participant data will be made available through the NIH RECOVER data repository in accordance with NIH data-sharing policies. If successful, this protocol will provide accessible tools that clinicians can use to address exercise intolerance and PEM in patients with Long COVID.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov - Platform: NCT06404047 ; Appendix A: NCT06404060 ; Appendix B: NCT06404073 . Registered on May 6, 2024.<br><br>RECOVER-ENERGIZE is a large, multicenter, randomized controlled platform trial that stratifies participants by PEM status, separately evaluating cardiopulmonary rehabilitation in those without significant PEM and structured activity pacing in those with PEM, while mitigating the risk of exertional harm.The structured activity pacing intervention is novel and has not previously been tested in a randomized trial in Long COVID. Its coach-delivered, video-conference format is designed to be easily implemented and scalable across diverse clinical settings.Patient, caregiver, and community representatives were integrally involved throughout protocol development, shaping eligibility criteria, intervention design, and selection of outcome measures, which strengthens the relevance of the trial to the Long COVID community.The trial combines a performance-based measure of endurance capacity (the Endurance Shuttle Walk Test) with a modified, PEM-specific patient-reported instrument (mDSQ-PEM). However, the nature of the interventions precludes blinding of participants and providers, and several key outcomes rely on self-report, which may introduce bias.},
}
@article {pmid42282698,
year = {2026},
author = {Davis, SE and Stern, DR and Inan, S and Vu, E and Lopez, D and Anwuri, F and Ghilotti, MG and Meissler, JJ and Unterwald, EM},
title = {Chronic cocaine exposure negatively impacts Long-COVID-like outcomes produced by the SARS-CoV-2 spike protein in the rat.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.02.729575},
pmid = {42282698},
issn = {2692-8205},
abstract = {Acute COVID-19 outcomes are exacerbated by substance use, however, the impact of substance use on Long-COVID is unknown. Here, we investigated the impact of chronic cocaine administration on spike-induced Long-COVID-like outcomes in the rat. Rats received intermittent chronic cocaine administration and a single intravenous injection of the SARS-CoV-2 spike protein. Two months following spike administration, Long-COVID-like outcomes were assessed. Exposure to spike protein in the presence of cocaine produced a persistent reduction in weight gain as compared with controls or spike protein alone. Further, cocaine-treated rats exposed to spike had lower withdrawal thresholds compared to control animals as well as their own baseline, suggesting increased pain sensitivity. Spike and/or cocaine increased the ratio of interleukin-6 (IL-6) to interleukin-10 (IL-10) levels in the hippocampus, indicating a shift towards a proinflammatory state. Paw withdrawal thresholds were positively correlated with IL-10 levels in the hippocampus and prefrontal cortex. Regarding olfaction, rats exposed to spike spent less time sniffing an odor attractant. Cocaine produced an anxiolytic-like phenotype during the elevated plus maze test. Further analysis of behaviors on the maze revealed that the latency to enter the open arms was shorter in rats exposed to spike or cocaine, suggesting a possible impulsive-like phenotype in these animals. These findings demonstrate the negative impact of cocaine on Long-COVID-like outcomes suggesting a need for increased clinical observations of people with co-occurring Long-COVID and cocaine use disorder.},
}
@article {pmid42283507,
year = {2026},
author = {Goldschmidt, MI and Mkoma, GF and Petersen, JH and Cederström, A and Agyemang, C and Rostila, M and Norredam, M and Benfield, T},
title = {Ethnic disparities, clinical severity and their relation to COVID-19 outcomes.},
journal = {Infectious diseases (London, England)},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/23744235.2026.2684566},
pmid = {42283507},
issn = {2374-4243},
abstract = {BACKGROUND: Ethnic inequalities in COVID-19 outcomes are extensively documented, yet underlying causes remain unclear. We investigated ethnic disparities in clinical severity at admission with COVID-19 and their relation to mechanical ventilation (MV), 60-day mortality, and long COVID.<br><br>METHODS: Retrospective cohort study of adults (&#x2265;18&#x2009;years) admitted with COVID-19 (March 2020-March 2022). Clinical and sociodemographic data extracted from patient records were linked to national register data. Using logistical regression, competing risk, and Cox proportional hazards models, we estimated risk of high-flow oxygen upon admission, MV, 60-day mortality, and long COVID comparing ethnic minority patients with patients of Danish origin.<br><br>RESULTS: Of 1610 patients, 39.1% were ethnic minority patients. Ethnic minorities were younger, had longer symptom duration (7 vs 6&#x2009;days, p&#x2009;<&#x2009;0.001), and a higher risk of requiring high-flow oxygen upon admission (OR 1.41, 95% CI: 1.12;1.79) than patients of Danish origin until adjusted for age. However, ethnic minorities were not at higher risk of MV (HR 1.00, 95% CI: 0.69;1.44), 60-day mortality (HR 0.81, 95% CI: 0.61;1.09), long COVID (HR 0.82, 95% CI: 0.56;1.19) or related symptom diagnosis (HR 1.32, 95% CI: 0.85;2.05).<br><br>CONCLUSION: While ethnic minorities presented later and more severely ill at admission with a higher risk of receiving high-flow oxygen, their risk of MV, 60-day mortality, and long COVID were comparable to patients of Danish origin. This was largely explained by a substantial difference in age. Our findings emphasise the need for public health interventions to ensure equitable and timely healthcare access for all populations.},
}
@article {pmid42283509,
year = {2026},
author = {Hansen, KT and Jensen, CB and Overgaard, R and Hansen, SN and Rask, CU and Fink, P and Nielsen, H and Dantoft, TM and Jørgensen, T and Thysen, SM and Rytter, D and Bech, BH},
title = {Fatigue, neurological, and cognitive symptoms after COVID-19 - a nationwide matched cohort study in Denmark.},
journal = {Infectious diseases (London, England)},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/23744235.2026.2684539},
pmid = {42283509},
issn = {2374-4243},
abstract = {OBJECTIVES: To investigate if COVID-19 increases the odds of fatigue, headache, dizziness, concentration difficulties, and memory impairment as well as at least three of these symptoms, at <4 weeks, 4-12 weeks, and >12 weeks after COVID-19. Additionally, we investigated whether symptoms were influenced by severity of COVID-19, sex, and pre-infection COVID-19 vaccination.<br><br>STUDY DESIGN AND METHODS: This study utilised data from the DanishBiCoVac cohort and national registers. The BiCoVac cohort collected information about symptoms through four questionaries distributed between May 2021 and May 2022. Participants with COVID-19 were matched to participants without COVID-19.Three matching samples were created according to time since COVID-19. Logistic regression was performed for the association between COVID-19 and each outcome.<br><br>RESULTS: Participants with COVID-19 within 0-4 weeks had higher odds of reporting all outcomes compared to participants without COVID-19. Between 4 and 12&#x2009;weeks after COVID-19, the odds of symptoms were also higher, although attenuated. After 12 weeks, participants with COVID-19 also had higher odds of symptoms except for concentration difficulties compared to those without COVID-19. Odds for symptoms were highest for participants reporting severe infection. Prior COVID-19 vaccination might weaken the association while no clear modification was found for sex.<br><br>CONCLUSION: Participants with COVID-19 had higher odds of all outcomes, especially within the first 4&#x2009;weeks. After 12&#x2009;weeks, the ORs were attenuated but still indicated an association for all outcomes except concentration difficulties. Individuals vaccinated against COVID-19 tended to report fewer symptoms after COVID-19. Participants with severe COVID-19 had the highest odds of symptoms.},
}
@article {pmid42263424,
year = {2026},
author = {Rishworth, A and Mant, M and Wilson, K and Iqbal, Z},
title = {Medical uncertainty, structural inequities and disease: The experiences of long-COVID among racialized immigrants and racialized non-immigrants in Canada.},
journal = {Social science &amp; medicine (1982)},
volume = {404},
number = {},
pages = {119478},
doi = {10.1016/j.socscimed.2026.119478},
pmid = {42263424},
issn = {1873-5347},
abstract = {Long COVID impacts millions of people worldwide, creating uncertain and varied symptoms that affect a range of bodily systems, with implications for individual and societal health and wellbeing. Yet, since there is no universal standardized way to diagnose long COVID, it has become a highly contested illness, with consequences for the recognition, resources, and responses directed towards the illness. While contested illnesses are known to foster discrimination via medical uncertainty, little is known about the synergistic effects of uncertainty, long COVID, and inequities. Research highlights that racialized individuals, immigrants, part-time workers, and low-income groups are disproportionately impacted by long COVID; however, knowledge gaps exist surrounding the ways long COVID uncertainties can compound, reproduce, and re-work existing fault lines of inequalities and patterns of disadvantage. This article examines the ways long COVID uncertainty shapes access, use, and control of health, economic, and political resources in Peel Region and how they converge to shape uneven lives. Findings from focus groups (n = 6) with racialized immigrants and non-immigrants managing long COVID reveal uncertainties surrounding long COVID reinscribe inequities by limiting access to critical health, socio-economic, and political resources needed for daily survival. The findings also reveal how long COVID uncertainties create new forms of by social suffering by delegitimizing, neglecting, and responsibilizing issues of long COVID, with implications for knowledge production, societal awareness, and policy creation. We close with a discussion of the impacts for policy and practice.},
}
@article {pmid42263781,
year = {2026},
author = {Jung, K and Kim, GA and Woo, J and Youn, J and Choi, EY and Bea, S and Choi, A and Kim, JH and Jang, H and Lee, DH and Joo, SK and Shin, JY and Kim, W},
title = {Ursodeoxycholic Acid and Long COVID in Steatotic Liver Disease: A Nationwide Cohort Study.},
journal = {Clinical and molecular hepatology},
volume = {},
number = {},
pages = {},
doi = {10.3350/cmh.2026.0283},
pmid = {42263781},
issn = {2287-285X},
abstract = {BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme 2, the cellular entry receptor for SARS-CoV-2, and may reduce acute COVID-19 severity. However, it remains unknown whether UDCA prevents long COVID outcomes in patients with steatotic liver disease (SLD)-a population vulnerable to adverse outcomes. We investigated the association between pre-infection UDCA use and risk of long COVID outcomes in patients with SLD.<br><br>METHODS: We conducted a nationwide retrospective cohort study using the Korean COVID-19 registry linked to National Health Insurance Service claims data (2019-2022). Patients with SLD (fatty liver index &#x2265;30) who experienced COVID-19 were included. Exposure was defined as at least one UDCA prescription within the 90 days preceding infection. Outcomes of interest were 20 incident long COVID conditions across eight organ systems assessed &#x2265;84 days post-infection. After propensity score (PS) fine stratification, hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression.<br><br>RESULTS: Among 469,108 patients with SLD and COVID-19, 23,560 (5.0%) were UDCA users. After PS fine stratification weighting, UDCA use was not associated with reduced risk for most long COVID outcomes. A protective association was observed for atrial fibrillation (HR 0.51, 95% CI 0.30-0.88), whereas increased risks were found for type 2 diabetes mellitus (HR 1.24, 95% CI 1.09-1.42) and epilepsy (HR 1.69, 95% CI 1.09-2.61).<br><br>CONCLUSIONS: Pre-infection UDCA use was not associated with reduced risk for most long COVID outcomes in patients with SLD. The observed associations warrant cautious interpretation given potential residual confounding and surveillance bias.},
}
@article {pmid42262130,
year = {2026},
author = {Yu, H-M and Zhu, M-L and Zhao, Y-L and Tan, J-X and Luo, S-C and Pang, P-P and Zheng, C-B},
title = {Research progress on the association between viruses and cardiac diseases.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0038326},
doi = {10.1128/jvi.00383-26},
pmid = {42262130},
issn = {1098-5514},
abstract = {Virus-related cardiac diseases encompass a diverse spectrum of cardiovascular pathologies caused by direct viral infection and indirect immune-mediated injury. Major cardiotropic and cardioactive viruses-including severe acute respiratory syndrome coronavirus 2, influenza virus, human immunodeficiency virus, arboviruses (dengue virus, chikungunya virus, Zika virus), enteroviruses (coxsackievirus B3), and human cytomegalovirus-contribute to myocardial injury manifesting as myocarditis, pericarditis, arrhythmias, acute and chronic heart failure, and thromboembolic complications. Mechanisms of cardiac involvement are multifactorial, involving direct infection of cardiac cells leading to cytopathic effects and innate immune activation, dysregulated adaptive immune responses promoting myocardial inflammation and fibrosis, electrophysiological disturbances, and systemic effects such as endothelial dysfunction and prothrombotic states that precipitate ischemic events. Clinical manifestations range from subclinical injury to fulminant myocardial inflammation and may also include long-term sequelae, such as post-acute cardiovascular symptoms, as observed in long COVID cases. Therapeutic strategies emphasize early antiviral treatment when effective agents exist, judicious immunomodulation based on viral replication status, and supportive management of cardiac dysfunction and arrhythmias. Prevention through vaccination, personal protective measures, vector control, and optimization of cardiovascular risk factors remains pivotal to reduce the burden of virus-associated cardiovascular diseases. Future research requires improved diagnostic precision, mechanistic elucidation, and randomized trials to optimize antiviral and immunomodulatory interventions and to develop vaccines for currently unmet viral targets. An integrated, mechanism-informed approach across prevention, acute management, and long-term care is essential to mitigate the cardiovascular morbidity and mortality attributable to viral infections.},
}
@article {pmid42263302,
year = {2026},
author = {Tyagi, A and Singh, K and Singh, PM and Gerges, FJ},
title = {Sympathetic and Parasympathetic Ganglion Blocks for Treatment of Long COVID-19 Symptoms: A Scoping Review.},
journal = {Pain physician},
volume = {29},
number = {3},
pages = {E151-E161},
pmid = {42263302},
issn = {2150-1149},
abstract = {BACKGROUND: Long COVID-19 affects approximately 10-30% of individuals who are infected with SARS-CoV-2 and is associated with persistent functional impairment and reduced quality of life. The heterogeneous, multisystemic nature and nonspecific symptomatology of long COVID-19 makes its treatment challenging. This scoping review evaluates existing evidence on sympathetic and parasympathetic ganglion blocks as potential interventions for patients suffering from long COVID-19.<br><br>OBJECTIVE: Our primary objective was to assess the effectiveness of sympathetic and parasympathetic ganglion blocks in treating patients with long COVID-19 by identifying the most commonly reported symptoms, symptom response to different block regimens, and any adverse effects associated with these interventions.<br><br>STUDY DESIGN: A scoping review.<br><br>SETTING: Outpatient clinics where patients received sympathetic blocks or parasympathetic blocks.<br><br>METHODS: A comprehensive search was conducted across PubMed, Embase, Cochrane CENTRAL, Web of Science, Google Scholar, and ClinicalTrials.gov using MeSH and free-text terms related to "long COVID-19," "post-COVID-19 syndrome," and "sympathetic ganglion blocks" and "parasympathetic blocks." Only English-language articles were included. Pre-print repositories and reference lists were also manually screened.<br><br>RESULTS: A total of 22 articles covering 505 patients were included in this review. The most frequently studied symptoms were olfactory dysfunction, fatigue, headache, and cognitive disturbances. The most commonly utilized intervention was the stellate ganglion block. The available evidence suggests that the stellate ganglion block could be an effective treatment for dysautonomia symptoms and cognitive dysfunction related to long COVID-19. Sphenopalatine ganglion block may be an effective option to treat headaches in long COVID-19 patients who are refractory to other treatments.<br><br>LIMITATIONS: The significant existing variations in treatment regimens precluded our ability to do a quantitative analysis. Reporting bias from case reports and small observational studies should also be considered.<br><br>CONCLUSIONS: Stellate ganglion blocks may offer therapeutic benefit for the dysautonomia and cognitive dysfunction associated with long COVID-19. Sphenopalatine ganglion blocks have shown promise in managing refractory headache symptoms in this population. Further well-designed, placebo-controlled randomized studies that employ validated outcome measures are required to establish the efficacy of sympathetic ganglion blocks in the treatment of long COVID-19.},
}
@article {pmid42259181,
year = {2026},
author = {Dickerson, A and Cruceanu, A and Pokharel, BR and Majumdar, N and Williams, F and Surabhi, K and Szatmari, EM and Eells, JB and Cook, PP and Akula, SM},
title = {Deciphering the miR-29c-3p / TET3 regulatory axis within the SARS-CoV-2-infected midbrain.},
journal = {Virology},
volume = {623},
number = {},
pages = {110989},
doi = {10.1016/j.virol.2026.110989},
pmid = {42259181},
issn = {1096-0341},
abstract = {Long COVID is increasingly associated with persistent neurological symptoms. Bioinformatic analysis identified multiple predicted miR-29c-3p binding sites in the 3'-UTR of Ten-Eleven-Translocation 3 (TET3). Luciferase reporter assays demonstrated that the miR-29c-3p is likely to bind an 8 base pair (bp) sequence within the 3'-UTR of TET3, supporting TET3 as a direct regulatory target. In vivo, an inverse relationship between miR-29c-3p and TET3 expression was observed in virus-positive midbrains from K18-hACE2 mice, while virus-negative and mock-infected midbrains showed no significant changes. The observation that only virus-positive brains showed decreased miR-29c-3p supports an alternative hypothesis that low base levels of miR-29c-3p expression may predispose the brain to viral neuro-invasion. Overall, miR-29c-3p > TET3 signaling emerges as a potential regulator of SARS-CoV-2-induced neurological consequences that warrants further investigation.},
}
@article {pmid42259512,
year = {2026},
author = {Ganesh, R and Nair, K and Grach, SL and Croghan, IT and Yadav, S and Hurt, RT and Mueller, MR},
title = {Persistent Cerebral 18-FDG PET Changes in Patients With Long COVID Presenting With Fatigue and Post Exertional Malaise.},
journal = {Journal of primary care &amp; community health},
volume = {17},
number = {},
pages = {21501319261458748},
doi = {10.1177/21501319261458748},
pmid = {42259512},
issn = {2150-1327},
abstract = {ObjectiveLong COVID (LC) refers to the long-term symptoms occurring after SARS-CoV-2 infection and resolution of the initial disease prodrome. While LC is increasingly recognized, knowledge about its biomarkers is still limited. This study examines imaging findings in [18]F-FDG PET-CT scans in 40 patients with LC from an academic LC Clinic, for potential imaging biomarkers.MethodsThis study included patients aged 18 and older with confirmed positive SARS-CoV-2 PCR test and at least 28 days post-symptom onset. [18]F-FDG PET-CT scans were performed, and brain metabolic activity was compared to a control database to generate Z-scores. Participants were grouped based on their clinical phenotype and Z-scores of different brain regions were analyzed using t-tests.ResultsThe study group was mainly female (70%), with a median age of 53 years, and predominantly non-Hispanic White (90%). Most had pre-existing conditions such as gastrointestinal, cardiovascular, endocrine, and psychiatric disorders. The findings showed significant cerebral hypometabolism in 29 patients with fatigue and post-exertional malaise (PEM), particularly in the left sensorimotor cortex (p=0.0253) and bilateral primary visual cortex (right: p=0.0096, left: p=0.0016), which persisted up to two years after infection.ConclusionsIn summary, this study identified persistent cerebral hypometabolism in LC patients, especially those with fatigue with PEM, up to two years post-infection. These results suggest that [18]F-FDG PET-CT could be a valuable tool for diagnosing and managing LC. Further research is essential to confirm these findings and improve treatment strategies for patients with LC.},
}
@article {pmid42261259,
year = {2026},
author = {Avdeev, SN and Ignatova, GL and Drapkina, OM and Popova, VB and Melnikova, EV and Chudinovskikh, TI and Ryabova, OV and Egorova, NV and Rubanik, TV and Shvarts, YG and Polyakova, SA and Antonova, AV and Zubkov, DA and Khmelevskii, MS and Khomyakova, NF and Tsyferov, MA and Hardman, TC and Tikhonov, AA},
title = {Bovhyaluronidase azoximer for long-term pulmonary sequelae of COVID19: a multicenter, randomized, double-blind, placebo-controlled study.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1080/17476348.2026.2684077},
pmid = {42261259},
issn = {1747-6356},
abstract = {BACKGROUND: Bovhyaluronidase azoximer (BA) has been reported to improve pulmonary function and exercise tolerance in patients with pulmonary sequelae of COVID-19. In this multicenter, randomized, double-blind, placebo-controlled study, we evaluated the effects of BA on patients with long-term (up to 12 months) pulmonary sequelae of COVID-19.<br><br>METHODS: Patients (n&#x2009;=&#x2009;392) were randomized 1:1 to receive BA or placebo every 5&#x2009;days for 71&#x2009;days. Percent predicted forced vital capacity (ppFVC), respiratory symptoms, and exercise tolerance indicators were assessed at baseline and on Days 71 (&#x394; ppFVC was the primary endpoint) and 180.<br><br>RESULTS: The pre-specified primary endpoint (&#x394; ppFVC at Day 71) was negative (+0.30%, p&#x2009;=&#x2009;0.817). Secondary endpoints showed reduced exertional desaturation (OR 0.36, p&#x2009;=&#x2009;0.006) and dyspnea (OR 0.62, p&#x2009;=&#x2009;0.040).<br><br>CONCLUSION: While the primary objective yielded clinically insignificant results, patients treated with BA showed increased exercise tolerance although further investigations are required to confirm findings.<br><br>TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (NCT06383819).},
}
@article {pmid42261335,
year = {2026},
author = {Cousins, O and Leeming, H and Putrino, D and Gordon, J},
title = {A new patient-led approach to building research infrastructure and evidence generation.},
journal = {Oxford open immunology},
volume = {7},
number = {1},
pages = {iqag009},
pmid = {42261335},
issn = {2633-6960},
abstract = {Over recent decades, patient and public involvement (PPI) has become a more established element of health research policy, although its implementation is often criticized for tokenism and for underrepresenting marginalized groups. In fields such as complex chronic illness (CCI), where formal research activity has historically been limited, conventional PPI frameworks have had little scope for meaningful application. Within this context, a new wave of patient-led initiatives has emerged that moves beyond participation in existing systems toward the creation of independent infrastructures for knowledge generation, extending the principle of "nothing about us, without us." This commentary examines Visible, a patient-founded health technology platform that combines daily energy-management tools with research infrastructure for CCIs. This infrastructure enables in-house data analyses and external collaborations, including app-based data studies, investigator-led research, and integration within clinical trials. We explore the advantages of this dual-purpose model, including greater inclusivity, sustained engagement, and richer longitudinal data. We also describe how embedding research functions within tools that patients find directly useful allows evidence generation and patient support to be mutually reinforcing.},
}
@article {pmid42247671,
year = {2026},
author = {Datta, B and Jaremski, JE and Wilkins, AS and Hoffman, Z},
title = {Assessing income heterogeneity of female sex as risk factor for long COVID: a meta-analytic investigation.},
journal = {Biodemography and social biology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/19485565.2026.2684735},
pmid = {42247671},
issn = {1948-5573},
abstract = {Women have a higher risk of Long COVID, defined as symptoms persisting for three or more months after SARS-CoV-2 infection. This study examines whether the elevated risk of Long COVID among women varies across income subgroups in a nationally representative sample of the U.S. population. Using data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS), we estimated adjusted odds ratios for Long COVID associated with female sex, stratified by four age categories and 11 income groups. We conducted random-effects meta-analyses of income subgroup estimates within each age category and assessed heterogeneity using Cochran's Q, I[2] statistics, prediction intervals, and Galbraith plots. Among younger age groups (18-34, 35-49, and 50-64 years), Cochran's Q ranged from 7.70 to 10.98 (p > 0.10), and I[2] was 0.00%, indicating no significant heterogeneity across income groups. In the ≥65 age group, Cochran's Q was 18.35 (p = 0.0494), and I[2] was 21.96%, suggesting modest heterogeneity. The 95% prediction interval for the ≥65 group (1.121-1.978) was wider than those for younger groups: 1.437-1.975 (18-34 years), 1.551-2.019 (35-49 years), and 1.355-1.766 (50-64 years).},
}
@article {pmid42250105,
year = {2026},
author = {Sultana, S and Asai, Y and Ishioka, H and Ikeda, S and Ohtera, A and Matsunaga, N and Ohmagari, N and Tsuzuki, S},
title = {Impact of long COVID on health-related quality-of-life among Japanese adults: findings of CARE Japan study.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {7},
pages = {},
pmid = {42250105},
issn = {1573-2649},
mesh = {Humans ; *Quality of Life ; Japan/epidemiology ; Female ; *COVID-19/psychology/epidemiology ; Male ; Middle Aged ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Aged ; Adult ; Surveys and Questionnaires ; SARS-CoV-2 ; East Asian People ; },
abstract = {OBJECTIVES: This study aimed to comprehensively assess the implications of long COVID on the health-related quality-of-life (HRQoL) among Japanese adults and to identify its associated factors.<br><br>METHODS: This study used prospective cohort data from the CARE Japan Study between January 2022 and January 2023. The outcome of this study was HRQoL, which was measured using SF-12 questionnaire. Self-reported long COVID was the primary independent variable. We fitted adjusted beta regression models to calculate beta regression coefficients with 95% confidence intervals (CI) and average marginal effects (AME) to explore the determinants of HRQoL. We also performed latent class analysis (LCA) to identify unobserved patterns of long COVID symptoms.<br><br>RESULTS: Final sample size was 1,285. Compared to the participants with no long COVID, the HRQoL among long COVID patients (&#x3b2;: -0.25; 95% CI: -0.36 to -0.14; AME: -0.036) was significantly lower. The effect of long COVID on HRQoL was the most pronounced among the respondents with pre-existing lung diseases (&#x3b2;: -0.72; 95% CI: -1.29 to -0.16; AME: -0.114). LCA identified three subgroups of long COVID patients - class 1, 2, and 3. Compared to the participants with no long COVID, participants belonged to class 1 (&#x3b2;: -0.47; 95% CI: -0.57 to -0.36; AME: -0.065), class 2 (&#x3b2;: -0.48; 95% CI: -0.60 to -0.35; AME: -0.066), and class 3 (&#x3b2;: -0.93; 95% CI: -1.06 to -0.79; AME: -0.148) had poorer HRQoL.<br><br>CONCLUSIONS: Long COVID patients had reduced HRQoL. Female gender, young-age, thin BMI or pre-existing psychological disorders were associated with lower HRQoL.},
}
@article {pmid42253394,
year = {2026},
author = {Jeriček Klanšček, H and Rehberger, M and Belščak Čolaković, A and Šinko, M and Lavtar, D and Hočevar Grom, A},
title = {Long COVID and Its Impact on Daily Functioning: Findings from the Si-Panda Behavioural Insights Survey in Slovenia.},
journal = {Zdravstveno varstvo},
volume = {65},
number = {2},
pages = {104-113},
pmid = {42253394},
issn = {0351-0026},
abstract = {INTRODUCTION: Research on the long-term consequences of COVID-19 has initially focused on the symptoms and prevalence of long COVID. However, few studies have fully incorporated the World Health Organization definition or explored its diverse predictors, including mental health factors. This study aims to deepen the understanding of long-term outcomes of COVID-19 and their associated factors.<br><br>METHODS: Data were drawn from the SI-PANDA Behavioural Insights survey on COVID-19, an online questionnaire administered to a selected sample of participants from an online access panel in Slovenia. The study included 5,961 participants aged 18 to 74. A multivariate logistic regression model was used to identify factors associated with reporting long COVID.<br><br>RESULTS: Among the 5,961 respondents, 3,234 reported having been infected with SARS-CoV-2 at least once. Of those, 38% reported persistent fatigue and lack of energy. Long COVID developed in 16.1% (n = 520) of respondents who had been infected. The factor most strongly associated with long COVID was experiencing at least one severe episode of COVID-19, which was associated with a fourfold increase in the odds (OR = 3.99; 95% CI: 3.25-4.91). Other significant associations were observed for risk of a depressive disorder (OR = 2.50; 95% CI: 1.79-3.44), three or more SARS-CoV-2 infections (OR = 2.30; 95% CI: 1.45-3.64), risky stress behaviour (OR = 2.10; 95% CI: 1.38-3.30), and the presence of at least one chronic disease (OR = 1.50; 95% CI: 1.24-1.91).<br><br>CONCLUSIONS: Understanding and effectively addressing infectious diseases like COVID-19 requires not only insight into the virus's biology and evolution but also recognition of the important role of mental health and psychological factors.},
}
@article {pmid42253978,
year = {2026},
author = {Tasoula, A and Arif, S and Waisberg, E and Bauer, L and Aslinger, E and Guarnieri, JW},
title = {Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1776555},
pmid = {42253978},
issn = {1664-3224},
abstract = {INTRODUCTION: Post-COVID Syndrome (PCS), or long-COVID, is a major public health burden, but its underlying mechanisms remain poorly understood. Because acute SARS-CoV-2 infection induces marked suppression of mitochondrial oxidative phosphorylation (OXPHOS), we investigated whether persistent immunometabolic remodeling is a recurring transcriptional, metabolic, and proteomic feature of PCS.<br><br>METHODS: We performed an integrated multi-omics analysis of transcriptomic, proteomic, and metabolomic datasets across multiple tissues from Syrian hamster models and human cohorts spanning acute infection through post-acute and PCS stages extending up to 12 months post-infection.<br><br>RESULTS: Across species and tissues, we observed overlapping signatures of mitochondrial dysfunction, including sustained suppression of OXPHOS, activation of mitochondrial stress responses, and enrichment of inflammatory pathways. Skeletal muscle exhibited the most pronounced and persistent mitochondrial repression in both hamsters and PCS patient biopsies, consistent with fatigue-associated phenotypes. Hamster heart and kidney tissues also showed persistent OXPHOS suppression, while lung tissue demonstrated prolonged inflammatory signaling despite partial metabolic recovery. In the nervous system, transcriptional profiles revealed region-specific patterns, including persistent cortical mitochondrial repression and partial recovery in sensory-associated regions. Peripheral blood mononuclear cells (PBMCs) transcriptomics and serum metabolic datasets suggested prolonged downregulation of OXPHOS-associated programs up to 12 months post-infection, potentially contributing to persistent immune dysregulation in susceptible individuals with underlying conditions. Longitudinal serum proteomics in PCS patients revealed sustained mitochondrial stress responses, increased oxidative stress signatures, and persistent immune activation at 1 and 6 months post-infection compared to recovered controls.<br><br>DISCUSSION: Together, these multi-omics results identify persistent mitochondrial repression and immune dysregulation as recurring features across PCS-associated datasets, providing a framework linking bioenergetic dysfunction with chronic immune activation and supporting future mechanistic and therapeutic investigation.},
}
@article {pmid42255427,
year = {2026},
author = {Lawal, B and Saidu Musa, S and Soe Thu, M and Ondee, T and Chatsirisakul, O and Pongpirul, K},
title = {Post-acute metabolic changes and risk of new-onset diabetes following COVID-19: a systematic review and meta-analysis.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1835180},
pmid = {42255427},
issn = {1664-2392},
abstract = {BACKGROUND: COVID-19 has been associated with persistent metabolic disturbances; however, the magnitude, consistency, and underlying mechanisms of post-infection alterations in glucose regulation remain incompletely characterized.<br><br>METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. PubMed and Embase were searched on December 18, 2024, for studies published from 2020 onward. Eligible studies included observational cohort and cross-sectional designs assessing metabolic outcomes at least three months after recovery from COVID-19.<br><br>RESULTS: Sixteen studies met inclusion criteria. Pooled analysis suggested a 41% increased risk of new-onset diabetes among COVID-19 survivors compared with non-infected individuals (RR 1.41, 95% CI: 1.38-1.44); however, this estimate was predominantly driven by a single large-scale study. Quantitative synthesis demonstrated higher HbA1c (SMD 1.44, 95% CI: 0.36-2.52) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD 0.96, 95% CI: 0.33-1.58), consistent with impaired glycemic control and increased insulin resistance. In contrast, fasting blood glucose (FBG) findings were inconsistent and highly heterogeneous (SMD 0.77, 95% CI: -0.40-1.94). Substantial heterogeneity was observed across outcomes.<br><br>CONCLUSION: COVID-19 may be associated with an increased risk of incident diabetes and persistent metabolic dysregulation. However, the limited number of studies contributing to pooled risk estimates and the influence of large registry-based data warrant cautious interpretation. These findings support consideration of metabolic monitoring and longitudinal follow-up in post-COVID care, particularly among individuals at elevated cardiometabolic risk.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42025630971.},
}
@article {pmid42258488,
year = {2026},
author = {Kaplan, DM and Kessler, N and Pozzo, NS and Doyle, CY and Dickey, P and Giordano, NA and Lehther, A and Maan, S and Mascaro, JS and McDowall, A and Peterson, S and Sirsi, H and Palitsky, R},
title = {Can consumer wearables support outpatient health monitoring for patients with post-acute infection syndromes? A systematic umbrella review of accuracy, validity, and clinical utility data.},
journal = {PLOS digital health},
volume = {5},
number = {6},
pages = {e0001124},
doi = {10.1371/journal.pdig.0001124},
pmid = {42258488},
issn = {2767-3170},
abstract = {An estimated 65 million individuals around the world have experienced Post-Acute Sequelae of SARS-CoV-2 infection (PASC or Long COVID) and an additional 17-24 million are living with other post-acute infection syndromes. Current frontline treatment recommendations for these heterogenous, multisystemic conditions emphasize self-monitoring and non-progressive rehabilitation of activity and exertion. Consumer health wearables can potentially support symptom, activity, and exertion tracking; however, the strength of the scientific evidence supporting their use in this context is unclear. This pre-registered systematic umbrella review aimed to address this gap by synthesizing review-level evidence for the accuracy, validity, and clinical utility of consumer wearable-assessed biometrics relevant to PASC and related syndromes. Following PRISMA guidelines, 3,988 records were screened, with 42 reviews meeting inclusion criteria spanning more than 30 brands and over 150 distinct device series. This umbrella review characterized quality and risk of bias, synthesized and evaluated accuracy evidence for 17 biometrics, and evaluated clinical utility outcomes. Findings revealed highly variable review quality; substantial heterogeneity in device performance across biometrics, populations, and settings; and limited evidence for clinical utility. Two biometrics-heart rate measurement and atrial fibrillation detection-had comparably stronger support. Strengths and limitations to the current evidence base are identified, along with recommendations for informed patient use and the further research needed to responsibly support the integration of consumer wearables into outpatient care pathways. A living umbrella review repository is provided on the Open Science Framework so that findings can be updated as new, review-level evidence for emergent technologies becomes available.},
}
@article {pmid42258788,
year = {2026},
author = {León-Herrera, S and Sánchez-Castro, M and Luisa Neves, A and Rodríguez-Pérez, MP and Jobim Fischer, V and Hutmacher, D and Aldakhil, R and Vaillancourt de Dios, M and Anjos de Almeida, V and Oliván-Blázquez, B and Magallón-Botaya, R and Benoy, C and Gómez-Bravo, R},
title = {Digital Interventions Addressing Cognitive and Psychological Symptoms in Long COVID: Scoping Review of Multicomponent Approaches.},
journal = {Interactive journal of medical research},
volume = {15},
number = {},
pages = {e80616},
doi = {10.2196/80616},
pmid = {42258788},
issn = {1929-073X},
abstract = {BACKGROUND: Long COVID, or postacute COVID-19 syndrome, presents with persistent cognitive and psychological symptoms such as brain fog, anxiety, depression, and fatigue, significantly impacting quality of life and daily functioning. Digital health interventions offer a scalable, accessible solution to bridge care gaps, especially where conventional neuropsychological support is limited. However, evidence regarding their effectiveness for neuropsychiatric symptoms in long COVID remains fragmented.<br><br>OBJECTIVE: This scoping review aimed to systematically identify and map the existing evidence on digital interventions targeting cognitive and psychological symptoms in individuals with long COVID. The review also sought to categorize intervention types, assess reported outcomes, and identify methodological gaps to inform future clinical and research priorities.<br><br>METHODS: The review followed the Arksey and O'Malley framework and adhered to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Comprehensive searches were conducted in 4 databases (PubMed, Scopus, Web of Science, and ScienceDirect) from December 2024 to February 2025. Eligible studies included peer-reviewed and gray literature published in English or Spanish since 2020. Studies were screened and selected based on predefined inclusion and exclusion criteria. Data were extracted using a standardized charting form and synthesized narratively, with thematic grouping by intervention type.<br><br>RESULTS: Of 888 records identified, 25 (2.82%) were included. Intervention types encompassed telehealth platforms, mobile health apps, virtual reality, online cognitive and psychological therapies, game-based cognitive training, neuromodulation (transcranial direct current stimulation), and multicomponent programs. Most studies reported improvements in psychological well-being, emotional regulation, and cognitive domains such as attention and memory. However, findings varied, with some interventions showing no significant cognitive gains or sustained effects. Common limitations included small sample sizes, lack of control groups, heterogeneity in outcomes and intervention protocols, and short follow-up durations. The underrepresentation of older adults and underserved populations was also noted.<br><br>CONCLUSIONS: Digital interventions show promise for addressing cognitive and psychological symptoms in long COVID, particularly when delivered as multicomponent programs. Nonetheless, the evidence base remains preliminary. Future research should prioritize high-quality randomized trials with standardized outcome measures, long-term follow-up, and diverse participant samples. Addressing barriers related to digital literacy and access will be essential to ensure equity and real-world effectiveness.},
}
@article {pmid42247342,
year = {2026},
author = {Borriello, M and Ranieri, R and Coppola, A and Lombari, P and Nevola, R and Marrone, A and Signoriello, G and Adinolfi, LE and Coppola, N and Ingrosso, D and Longo, FM and Di Maro, C and Alfieri, CM and Ingrosso, D and Simeoni, M and Perna, A},
title = {Inflammatory biomarkers in the assessment of kidney function decline in Long Covid syndrome.},
journal = {Kidney &amp; blood pressure research},
volume = {},
number = {},
pages = {1-24},
doi = {10.1159/000552904},
pmid = {42247342},
issn = {1423-0143},
abstract = {INTRODUCTION: Long Covid (LC) is an inflammatory condition, affecting multiple organs, including kidneys. This study aims to identify a signature of inflammatory biomarkers that can predict, describe, and monitor kidney function decline in LC patients.<br><br>METHODS: A single-center observational study was carried out at the COVID Center of University of Campania "L. Vanvitelli". Patients who survived the acute phase, were invited for a follow-up visit at least 12 months after discharge. Based on estimated Glomerular Filtration Rate (eGFR), patients were categorized in three groups: Group 1: eGFR > 90 ml/min x 1.73 m2, Group 2: eGFR 30-89 ml/min x 1.73 m2, and Group 3: eGFR < 30 ml/min x 1.73 m2. The multiplex ELLA platform was employed to quantify serum levels of inflammatory biomarkers including IL-6, IL-17, IL-10, IL-1&#xdf;, PTX3, TNF-a, VCAM-1, ICAM-1 and E-Selectin. Associations between each biomarker level and eGFR were analyzed.<br><br>RESULTS: A decline in eGFR at follow-up compared to admission was observed. IL-6 levels increased significantly as the eGFR decreased across the groups. IL-17, IL-10 and VCAM1 levels were markedly elevated in Group 3.<br><br>CONCLUSIONS: According to our results, IL-6, IL-17, IL-10 and VCAM1 constitute a biomarker signature associated with poorer renal prognosis in LC patients. The rise in IL-6 could drive the increase in IL-17, IL-10 and VCAM1 rise, contributing to kidney function decline. These findings may help establish a clinical and laboratory framework to predict chronic kidney disease (CKD) risk in LC. Furthermore, ELLA platform appears as a useful tool for inflammatory biomarker quantification in the clinical setting.},
}
@article {pmid42241251,
year = {2026},
author = {Reeves, JM and McNab, J and Spencer, LM and Tsai, LL and Baillie, AJ and Alison, JA},
title = {Clinician perspectives on Long-COVID physical rehabilitation: challenges, uncertainty, and semantics.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/09638288.2026.2682998},
pmid = {42241251},
issn = {1464-5165},
abstract = {PURPOSE: To understand the perspectives of clinicians who provided rehabilitation services to people with Long-COVID or referred people to such services.<br><br>METHODS: Clinicians involved with Long-COVID rehabilitation were recruited via email and interviewed. Recruitment continued until thematic saturation on physical rehabilitation approaches was reached. Semi-structured interviews were recorded, deidentified, and transcribed. Reflexive thematic analysis was used to develop themes from codes.<br><br>RESULTS: Twenty-one clinicians were interviewed about their perceptions of Long-COVID rehabilitation. Clinicians were physiotherapists, exercise physiologists, clinical psychologists, respiratory physicians, rehabilitation physicians, an infectious disease physician, and a general practitioner. Four overarching themes were identified. (1) "Long-COVID is hard to characterise," including Subtheme 1.1 "Naming Long-COVID: opinions and impacts of differing terminology"; and 1.2 "Framing Long-COVID: one syndrome, experienced as many." (2) "Challenges of diagnosis in a novel condition." (3) "Management of a novel condition - Who knows what to do?" (4) "Exercise therapy is complex," including Subtheme 4.1 "Graded exercise therapy - semantic discordance despite alignment in approach" and 4.2 "Clinicians question public opposition to exercise."<br><br>CONCLUSION: Clinicians described Long-COVID as a heterogenous condition which challenges traditional rehabilitation frameworks. This study highlights how uncertainty with rehabilitation methods leads to fragmented approaches to rehabilitation and inconsistencies in care.},
}
@article {pmid42243809,
year = {2026},
author = {Nielsen, TB and Sørensen, D and Hawkins, J and Nielsen, CV and Leth, S and Schiøttz-Christensen, B and Laursen, CH and Oestergaard, LG},
title = {Exploring the implementation of a long COVID rehabilitation intervention: a mixed-methods process evaluation.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14876-6},
pmid = {42243809},
issn = {1472-6963},
abstract = {BACKGROUND: Long COVID is recognised as a global public health concern, creating demand for rehabilitation. Despite a growing evidence base on long COVID rehabilitation interventions, knowledge of the implementation of these interventions remains limited, constraining adaptation and transfer across health care settings. In a previous study, the programme theory of a Danish community-based long COVID rehabilitation intervention was refined. However, uncertainties regarding its implementation remain. This study therefore aimed to explore the delivery and implementation of The Long COVID Rehabilitation Intervention.<br><br>METHODS: This convergent mixed-methods process evaluation focused on what was delivered (reach, fidelity, and dose) and how it was delivered (implementation processes and adaptations). Quantitative data comprised baseline patient questionnaires and routine rehabilitation patient records. Qualitative data comprised a focus group interview with health professionals and an individual interview with the rehabilitation centre manager. Quantitative data were analysed descriptively, and qualitative data were analysed using content analysis. Findings were integrated narratively.<br><br>RESULTS: In total, 336 patients were included of whom 325 patients were referred for rehabilitation and 321 initiated the programme. Most patients were female, had a long education and were employed or enrolled in education prior to their COVID-19 disease. Median rehabilitation length was 183 days (IQR 131-261), and the patients received a median of 13 sessions (IQR 8-22). Overall, key intervention activities were consistently delivered. Most rehabilitees received a combination of individual and group-based sessions, with the energy management group being the most common. Variation over time was observed in median rehabilitation length and number of sessions delivered, reflecting adaptations to the intervention over time. Adaptations and implementation were influenced by contextual conditions concerning flexible delivery within a clear structure, knowledge of long COVID, space for reflection and adaptation, and organisational recognition and legitimacy.<br><br>CONCLUSIONS: This paper reports the implementation and delivery of The Long COVID Rehabilitation Intervention and highlights key contextual conditions that shaped these processes. These findings may inform adaptation and transfer of similar rehabilitation interventions to other health care settings. Future development and adaptation of long COVID rehabilitation should explicitly consider equity in access to ensure rehabilitation services reach diverse patient groups.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT06544382. Registered retrospectively on 9 August 2024.},
}
@article {pmid42245008,
year = {2026},
author = {Abd-Eldayem, MA and Vinayagam, M and Vance, YA and Paranjape, SY and Wanjalla, CN and Hunter, KC and Dikalov, S and Diedrich, A and Kulapatana, S and Mehr, PE and Solis-Montenegro, TX and Harrison, DG and Shibao, CA},
title = {Monocyte Oxidative Stress Underlies Persistent Immune Activation in Long COVID Postural Orthostatic Tachycardia Syndrome.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.08.26352776},
pmid = {42245008},
abstract = {Long COVID Postural Orthostatic Tachycardia Syndrome (LCPOTS) is characterized by persistent orthostatic tachycardia and systemic symptoms following SARS-CoV-2 infection. Many features of LCPOTS suggest ongoing immune activation, but the mechanisms driving this response remain unclear. In this study, we show that patients with LCPOTS, compared with individuals who recovered from SARS-CoV-2 without POTS, exhibit increased monocyte mitochondrial content and superoxide production, along with downregulation of NRF2-dependent antioxidant enzymes. This is accompanied by a marked increase in the formation of isolevuglandins (IsoLGs) in monocytes, which modify self-proteins and act as neoantigens capable of activating T cells. Consistent with this, LCPOTS patients exhibit a 3-fold increase in circulating T cell-monocyte doublets with immunological synapse formation. T cells in these complexes display a proinflammatory effector-memory and TEMRA phenotype, producing IFN-γ and IL-17A, which correlated with symptom severity. Circulating cytokines, including IL-17A, IFN-γ, and TNF-α, are elevated in patients with LCPOTS by 1.5 to 3-fold. This immune response likely drives systemic inflammation and impaired cardiovagal regulation, hallmarks of LCPOTS. Our findings suggest that monocyte oxidative stress and IsoLG neoantigen formation sustain T cell activation, linking immune dysregulation to cardiovagal dysfunction. Targeting these pathways may offer novel therapeutic opportunities.},
}
@article {pmid42245774,
year = {2026},
author = {Wilk, T and Simeonova, E and Akee, R and Carroll, S and Ponce, NA},
title = {The Disproportionate Burden: Health and Economic Outcomes of COVID-19 for Native American Communities.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9452333/v1},
pmid = {42245774},
issn = {2693-5015},
abstract = {Background American Indian and Alaska Native (AIAN) populations experienced disproportionate health and economic impacts during the COVID-19 pandemic. While prior research has documented elevated infection and mortality rates among Indigenous communities, less is known about the persistence of COVID-19 symptoms and their potential economic consequences. This study examines differences in COVID-19 infection, long-COVID symptoms, and pandemic-related economic hardship among AIAN populations in California. Methods We analyzed adult responses from the California Health Interview Survey (CHIS) from 2021-2023, including the public-use files and a restricted oversample of AIAN communities. Multivariate generalized linear models were used to estimate associations between demographic, socioeconomic, and health characteristics and seven COVID-19 related outcomes, including infection, long-COVID symptoms, vaccination status, testing behavior, food insecurity, job loss, and reductions in work hours to produce survey weighted population-representative estimates. Results AIAN respondents reported higher rates of COVID-19 infection and long-COVID symptoms than non-AIAN respondents. Estimates indicate 47% of AIAN respondents reported testing positive for COVID-19 and 40% reported long-COVID symptoms, compared with 30% among non-AIAN respondents. Obesity and poverty were positively associated with infection and long-COVID symptoms. Long-COVID symptoms were positively associated with food insecurity and job loss, while vaccination was associated with lower probabilities of job loss and reductions in hours or income. Conclusions Persistent COVID-19 symptoms may contribute to ongoing economic vulnerability in AIAN communities. Structural factors including poverty, chronic health conditions, and limited access to healthcare amplify the long-term health and economic consequences of the pandemic.},
}
@article {pmid42246405,
year = {2026},
author = {Zheng, Z and Yousefi, M and Marks, M and Dixit, A and Wahid, R and Viscidi, E and Anderson, EJ},
title = {A narrative review of COVID-19 epidemiology and mRNA vaccine impact in children &lt; 12 years during the omicron era (November 2021 - December 2025).},
journal = {Expert review of vaccines},
volume = {},
number = {},
pages = {2684961},
doi = {10.1080/14760584.2026.2684961},
pmid = {42246405},
issn = {1744-8395},
abstract = {INTRODUCTION: COVID-19 continues to pose a burden in children under 12 years of age during the Omicron era (November 2021 - December 2025). Following Omicron's emergence, SARS-CoV-2 seroprevalence increased rapidly, with most children infected by ages 2-4 years. Pediatric hospitalization rates declined after the initial Omicron wave but remained elevated in children under 2 years and in those with underlying conditions. While healthy children typically experience mild illnesses, severe outcomes - including hospitalization, admission to intensive care unit, death, and multisystem inflammatory syndrome - can occur, particularly in unvaccinated children.<br><br>AREAS COVERED: This narrative review summarizes current evidence on pediatric COVID-19 epidemiology and vaccine impact, including infection rates, severe outcomes, post-acute COVID-19 syndrome (Long COVID), and mRNA vaccine effectiveness and uptake in high-income regions. A literature search included peer-reviewed publications, surveillance data, and reports from health agencies during the Omicron era.<br><br>EXPERT OPINION: mRNA vaccines are effective in reducing pediatric COVID-19-related morbidity, but uptake remains low globally. Addressing parental concerns, improving vaccine accessibility, and promoting evidence-based communication are critical to increasing uptake. Given the continued disease burden and the potential for severe outcomes, ensuring access to mRNA COVID-19 vaccines for children at higher risk and for families who wish to vaccinate their children is beneficial.},
}
@article {pmid42236640,
year = {2026},
author = {Ngiam, JN and Loy, EX and Koh, MCY and Chiew, CJ and Li, RJ and Lim, SC and Tai, ES and Bee, YM and Chow, WL and Lye, DCB and Chia, YW and Chan, MYY and Hausenloy, DJ and Tan, KB and Wee, LE},
title = {Prior SGLT2 Inhibitor and Metformin Use and Risk of Long COVID in Type 2 Diabetes: A Nationwide Population-Based Cohort Study.},
journal = {Infectious diseases and therapy},
volume = {},
number = {},
pages = {},
pmid = {42236640},
issn = {2193-8229},
abstract = {INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of post-acute sequelae after COVID-19 (PASC). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and metformin may have systemic benefits beyond glycemic control. We evaluated the impact of prior SGLT2i and metformin use on the risk of post-acute COVID-19 complications.<br><br>METHODS: We conducted a retrospective, population-based cohort study using national healthcare claims databases, from July 1, 2021 to February 28, 2023. Cohorts were stratified based on SGLT2i or metformin, against patients had not received these medications. Overlap weighting was applied to adjust for baseline differences in demographics, vaccination status, comorbidities, and prior healthcare utilization. Competing-risks regression models were used to assess differences in the risk of long-COVID outcomes between 31 and 300&#xa0;days post-infection.<br><br>RESULTS: Among 71,698 patients with T2DM, 22,501 (31.4%) had prior SGLT2i use, and 66,792 (93.1%) had prior metformin use. Compared with non-SGLT2i users, patients treated with&#xa0;SGLT2i had a significantly lower risk of neurological sequelae (aHR&#x2009;=&#x2009;0.60 [0.45-0.81]), particularly memory and cognitive impairment (aHR&#x2009;=&#x2009;0.63 [0.41-0.98]). SGLT2i was also associated with a reduced risk of post-acute symptoms (aHR&#x2009;=&#x2009;0.87 [0.77-0.99]). Metformin use was associated with significantly lower risk of composite post-acute outcomes (aHR&#x2009;=&#x2009;0.80 [0.68-0.96]) and post-acute symptoms (aHR&#x2009;=&#x2009;0.77 [0.63-0.93]). Amongst patients on metformin, the addition of SGLT2i further lowered the risk of neurological sequelae (aHR&#x2009;=&#x2009;0.81 [0.71-0.93]) and composite symptoms (aHR 0.87 [0.76-0.99]).<br><br>CONCLUSION: SGLT2i and metformin use were associated with a lower risk of PASC and post-acute symptoms. There may be additional protective benefits when both agents are used concurrently.},
}
@article {pmid42236766,
year = {2026},
author = {Lamprecht, PS and Streese, L and Hauser, C and Hanssen, H and Lorenz, M and Klee, S and Proquitté, H and Vilser, D},
title = {Retinal microvascular alterations consistent with endothelial dysregulation in paediatric post-COVID-19 syndrome: A prospective matched-cohort study.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42236766},
issn = {2045-2322},
abstract = {Persistent symptoms following SARS-CoV-2 infection in children remain poorly understood, and objective biological correlates are scarce. The vascular endothelium is considered a central target of post-viral dysregulation, yet paediatric evidence for microvascular involvement is limited. Retinal imaging enables non-invasive assessment of microvascular structure and function and may help to clarify whether endothelial dysregulation is present in children with post-COVID-19 syndrome (PCS). Retinal vessel diameters and flicker-induced vasoreactivity were assessed at baseline and after a median of 14 weeks. Compared with matched healthy controls, multivariable analyses showed that PCS independently predicted wider central retinal arteriolar equivalent (CRAE + 28.1 μm, 95% CI 21.7-34.5, p < 0.001) and central retinal venular equivalent (CRVE + 21.7 μm, 95% CI 15.8-27.7, p < 0.001), with a higher arteriolar-to-venular ratio (AVR + 0.038 units, 95% CI 0.012-0.064, p = 0.005). These findings suggest a distinct microvascular pattern in children with PCS that is consistent with endothelial dysregulation months after infection. While no significant group-level changes were observed at follow-up, children with particularly large venular diameters and reduced flicker responses showed the greatest improvement. Longer follow-up intervals predicted decreasing venular diameter, and reductions in symptom burden correlated with increasing AVR over time. Together, these results indicate heterogeneous, time-dependent changes in microvascular parameters. Retinal vessel analysis may provide a useful, non-invasive approach to characterising vascular involvement in paediatric PCS and improving understanding of post-viral sequelae.},
}
@article {pmid42237176,
year = {2026},
author = {Kim, H and Kwak, E and Lee, D and Lee, S and Lee, D and Ko, SJ and Baik, M and Paik, JW and Sim, M and Jung, SJ},
title = {Mental Health Outcomes After the Acute Phase of COVID-19: Factors Identified in a Korean Public Mental Health Service.},
journal = {Journal of Korean medical science},
volume = {41},
number = {21},
pages = {e165},
doi = {10.3346/jkms.2026.41.e165},
pmid = {42237176},
issn = {1598-6357},
support = {HI22C0505//Korea Health Industry Development Institute/Republic of Korea ; },
abstract = {BACKGROUND: Sequelae following coronavirus disease 2019 (COVID-19) frequently include lasting neuropsychiatric symptoms; however, identifying predictors from the acute phase remains challenging due to limitations in collecting prospective data during that time.<br><br>METHODS: Data were obtained from electronic counseling records of 515 COVID-19 patients who received free services from the Korean National Center for Disaster and Trauma. The Clinical Global Impression Severity Scale (CGI-S) was used to repeatedly assess mental health at each counseling session. Baseline predictors included demographic characteristics, psychiatric and medical comorbidities, and psychological response, which was further divided into four sub-factors via factor analysis. Multivariate mixed effect models were used to explore the relationship between these predictors and mental health following the acute phase of COVID-19, with analyses stratified by gender.<br><br>RESULTS: The most common post-COVID psychological responses were anxiety, depression, and sleep problems, with CGI-S scores dropping from 2.83 initially to 1 by the last observed session and averaging 2.38 at the third follow-up. Four sub-factors were identified through exploratory factor analysis, namely cognitive and physical exhaustion, emotional distress, self-destructive coping, and somatized anxiety. Baseline psychological responses (&#x3b2; = 0.06, P < 0.001) and pre-existing psychiatric disorders (&#x3b2; = 0.37, P < 0.001) were significantly associated with higher CGI-S scores over time; among psychological sub-factors, cognitive-physical exhaustion (&#x3b2; = 0.28, P < 0.001), emotional distress (&#x3b2; = 0.32, P < 0.001), and self-destructive coping (&#x3b2; = 0.12, P < 0.001) were significant predictors, with emotional distress significant in men (&#x3b2; = 0.26, P = 0.001) and both cognitive-physical exhaustion (&#x3b2; = 0.36, P < 0.001) and emotional distress (&#x3b2; = 0.36, P < 0.001) significant in women.<br><br>CONCLUSION: Baseline psychological responses predict persistent mental health symptoms, and identified profiles may help early identification of high-risk groups during acute COVID-19.},
}
@article {pmid42238391,
year = {2026},
author = {Laxton, CS and Tabachnikova, A and Cooke, L and Wang, K and Blaser, S and Silva, J and Wood, J and Nam, HS and Lu, Z and Miller, C and Rodrigues, G and Fisher, V and Guirgis, C and Hooper, WB and Lee, A and Doerstling, M and Bhattacharjee, B and Guan, L and Putrino, D and Iwasaki, A},
title = {Analysis Of Salivary Herpesviruses Reveals Associations Between HHV-6 And Long COVID Severity.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.19.26353495},
pmid = {42238391},
abstract = {BACKGROUND: Reactivation of human herpesviruses (HHVs), particularly EBV, is associated with more severe acute SARS-CoV-2 infections and the development of Long COVID (LC). Observations of higher anti-EBV antibody levels in individuals with LC support the idea that chronic reactivation of HHVs could contribute to LC pathology. HHV shedding in saliva has also been previously associated with saliva hormone levels. This study aims to examine the relationship between salivary shedding of HHV DNA and LC symptoms, as well as cortisol, testosterone, and estradiol levels.<br><br>METHODS: We enrolled 45 participants with LC, and 45 age-sex-matched controls. Surveys and validated health questionnaires were used to collect demographics, medical history, and symptom profiles. Saliva was self-collected at waking, 15, 30, and 45 minutes, and 8 and 16 hours after waking, across two consecutive days. Salivary cortisol, testosterone and estradiol were measured, and extracted nucleic acid was tested for EBV, HSV 1/2, HCMV and HHV-6 A/B using multiplex qPCR, plus SARS-CoV-2 and RNaseP using RT-qPCR.<br><br>FINDINGS: Detection of salivary EBV and HHV-6 DNA was highest early in the morning. There were no significant differences in salivary cortisol, testosterone, or estradiol, or in EBV or HHV-6 shedding between the LC and control groups. However, salivary HHV-6 DNA levels were positively associated with a greater aggregated LC propensity score, as well as anxiety and depression scores.<br><br>INTERPRETATION: The observed correlation between salivary HHV-6 shedding and symptom severity suggests HHV-6 may contribute to post-acute disease, though mechanisms remain unclear. While our study did not identify a relationship between salivary EBV shedding and LC, EBV may still play a role at earlier time points in the disease course, or in compartments not sampled here. These findings highlight the potential importance of HHV-6 in LC pathophysiology and underscore the need for longitudinal, multi-compartment studies of herpesvirus reactivation in LC.},
}
@article {pmid42239825,
year = {2026},
author = {Pucci, SL and Veide, A and Pierce, H and Kaminski, D},
title = {The expanding potential of low-dose naltrexone in clinical practice with a focus on long COVID.},
journal = {The mental health clinician},
volume = {16},
number = {3},
pages = {125-128},
pmid = {42239825},
issn = {2168-9709},
}
@article {pmid42240437,
year = {2026},
author = {White, LJ and Biberston, JD and Jakubski, SJ and Boulifard, DA and Cooper, ES and Beckett, CG and Letizia, AG and Porter, CK},
title = {Lung Function in Young, Active Duty U.S. Marines After SARS-CoV-2 Infection.},
journal = {Military medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/milmed/usag247},
pmid = {42240437},
issn = {1930-613X},
support = {//Defense Health Agency and Defense Advanced Research Projects Agency/ ; },
abstract = {INTRODUCTION: Post-acute sequelae of SARS-CoV-2 (PASC) or long COVID may lead to an array of adverse health outcomes in young, otherwise healthy adults, potentially limiting warfighter readiness. This study assessed pulmonary function in Marines to evaluate associations between acute and chronic symptoms of COVID-19 and abnormal spirometry. The data were obtained within the framework of the COVID-19 Health Action Response for Marines (CHARM) study, a larger effort aimed at characterizing PASC in this population.<br><br>MATERIALS AND METHODS: Pulmonary function testing (PFT) was performed using portable spirometry on Marine participants in CHARM 2.0 from February 2021 to April 2022. Pulmonary symptoms were characterized as mild, moderate, or severe based on self-report. Participants with symptoms &#x2265;30 days were characterized as having PASC. Individual pulmonary reports were classified as either normal or abnormal. Statistical analyses examined the relationship between pulmonary symptoms and PFT results.<br><br>RESULTS: A total of 889 Marines (mean age: 19 years) completed PFTs. Among the 798 COVID-19-positive participants, 61% reported symptomatic infection and 24.7% reported PASC. Data indicated significant reduction in the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), forced vital capacity (FVC), the forced expiratory flow generated during the middle half of the FVC measurement (FEF25%-75%), and the peak expiratory flow (PEF) among participants with acute symptoms of dry cough and/or wheezing, as well as chronic symptoms. Despite inverse correlations between several PFT metrics and symptom severity, a significantly greater proportion of participants without a dry cough had more abnormal FVC scores than those with a mild dry cough.<br><br>CONCLUSIONS: The chronic effects of COVID-19 in young, healthy adults remain understudied, likely because of the high prevalence of mild or asymptomatic infections, despite recent evidence suggesting these individuals may be at risk for PASC. In this cohort, PEF and PEF% predicted abnormalities were observed but are not consistently included in standard interpretations, representing a potential gap between symptoms and objective findings. These results may provide a useful baseline for assessing future respiratory viral exposures and subclinical lung function changes.},
}
@article {pmid42240559,
year = {2026},
author = {Bramante, CT and Stewart, TG and Boulware, DR and McCarthy, MW and Gao, Y and Rothman, RL and Mourad, A and Thicklin, F and Cohen, JB and Garcia Del Sol, IT and Shah, NS and Mehta, M and Quintero Cardona, O and Scott, J and Ginde, AA and Castro, M and Jayaweera, D and Sulkowski, M and Gentile, N and McTigue, K and Felker, GM and Collins, S and Dunsmore, SE and Adam, SJ and Lindsell, CJ and Hernandez, AF and Naggie, S and , },
title = {Metformin on the Presence of COVID-19 Symptoms 6 Months after Infection: The ACTIV-6 Randomized Clinical Trial.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag335},
pmid = {42240559},
issn = {1537-6591},
abstract = {BACKGROUND: We conducted a quadruple-blinded, randomized, placebo-controlled trial of metformin for treating acute SARS-CoV-2 infection to prevent long COVID symptoms in low-risk adults.<br><br>METHODS: The ACTIV-6 platform evaluated repurposed medications for mild to moderate COVID-19. Between September 19, 2023 and May 1, 2024, 2983 outpatient adults &#x2265;30 years with confirmed SARS-CoV-2 infection and &#x2265;2 COVID-19 symptoms were included within 7 days of symptom onset from 90 sites. Participants were randomized to metformin or placebo for 14 days. Post-acute sequelae of SARS-CoV-2 or death (PASCD) was ascertained by asking whether participants had symptoms they attributed to COVID-19 on day 180. Secondary outcomes included clinician-diagnosed long COVID.<br><br>RESULTS: The median age was 47 years (interquartile range 38-57); 63% were female; 47% Hispanic/Latino; 83% reported &#x2265;1 prior COVID-19 infections or &#x2265;2 SARS-CoV-2 vaccines. There were no deaths. Overall, 96 (3.2%) reported COVID-19 symptoms on day 90, 101 (3.4%) on day 120, and 79 (2.6%) on day 180. The adjusted risk of symptoms on day 180 was 0.8 percentage points lower with metformin (95% credible interval [CrI] -2.2 to 0.6) with a posterior probability of efficacy [PPE] for preventing symptoms of 0.83, risk ratio 0.79 (95% CrI 0.474 to 1.230). Compared with placebo, the risk of clinician-diagnosed long COVID was 0.7 percentage points lower with metformin (95% CrI -1.5 to 0.1); PPE 0.96; risk ratio 0.495 (95% CrI 0.155 to 0.995).<br><br>CONCLUSIONS AND RELEVANCE: In low-risk adults, most with prior immunity, metformin did not exceed the efficacy threshold of 0.975 for PASC. Metformin reduced the risk of clinician-diagnosed long COVID.},
}
@article {pmid42241126,
year = {2026},
author = {Walker, GR},
title = {Multi-Modal Sensoriality and Online Community-Based Support in the Long Covid Choir.},
journal = {Medical anthropology},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/01459740.2026.2676659},
pmid = {42241126},
issn = {1545-5882},
abstract = {Long covid involves diverse chronic physical and cognitive symptoms with poorly understood mechanisms and limited treatment options. Many affected individuals turn to community groups for support. Drawing on ethnographic research with the Long Covid Choir, a patient-run online singing and support group, in this paper I examine how participants use overlapping sensory experiences to cultivate belonging, foster biosocial solidarity, structure care, and counter isolation. Through shared auditory and visual practices - collective breathing, guided mindfulness, and gentle stretching - the choir cultivates multi-sensory connection. These activities foster digitally mediated social intimacy for individuals who face significant barriers to in-person participation.},
}
@article {pmid42228823,
year = {2026},
author = {Perestiuk, VO and Kosovska, TM and Volianska, LA and Boyarchuk, OR},
title = {Impact of War-Related Internal Displacement on the Course and Consequences of COVID-19 in Ukrainian Children.},
journal = {Turkish archives of pediatrics},
volume = {61},
number = {6},
pages = {531-542},
doi = {10.65717/TurkArchPediatr.2026.25353},
pmid = {42228823},
issn = {2757-6256},
support = {0123U100301//Ministry of Health of Ukraine/ ; },
abstract = {OBJECTIVE: The aim of the study was to compare the key clinical features and course of SARS-CoV-2 infection between the local population of the Ternopil region and internally displaced persons (IDPs), to analyze the quality of life in both participant groups, and to determine the frequency and symptoms of long COVID.<br><br>METHODS: A cross-sectional study was conducted involving children with confirmed COVID-19 from September 2022 to May 2024. Clinical symptoms, COVID-19 severity, 25(OH)D and zinc levels, long COVID symptoms, and quality of life were compared between internally displaced and local populations using structured questionnaires and medical records.<br><br>RESULTS: A total of 299 children with COVID-19 were included, consisting of 29 IDPs and 270 local population. Gastrointestinal symptoms were significantly more common among IDPs (P<.0001), while respiratory symptoms and severe fatigue predominated in the local population (P < .0001 and P=.0229, respectively). The IDPs experienced a more severe course of COVID-19 (P=.0141) and had a longer duration of hospital stay (P < .0001). Serum zinc levels were significantly lower in IDPs compared to local population (P=.0229). Assessment of quality of life demonstrated higher total, physical, psychosocial, and school functioning scores among IDPs, indicating a statistically better perceived health status. The overall frequency of long COVID did not differ between groups; however, its distribution varied by age: it was significantly higher in IDPs under 6 years (P=.0062), whereas among children &#x2265;6 years, it was more common in the local population (P=.0092). Age-specific differences in long COVID symptom patterns were also observed between IDPs and local children.<br><br>CONCLUSION: This study highlights the need to consider the impact of war, displacement, and chronic stress on the clinical presentation, timeliness of seeking care, and symptom reporting among children with COVID-19. Future efforts should focus on improving access to healthcare, health education, nutritional, and psychosocial support for displaced children to mitigate the combined negative effects of COVID-19 and war.},
}
@article {pmid42229803,
year = {2026},
author = {George, JC and Kulikowicz, T and Bombard, PT and Rossi, M and Dumm, AJ and Anderson, OM and Sommers, JA and Brosh, RM},
title = {SARS-CoV-2 Nsp13 Helicase Resolves G-Quadruplexes and is Inhibited by G4 Ligands or an Anti-Viral Regulator: Implications for G4 Anti-Coronavirus Therapies.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113214},
doi = {10.1016/j.jbc.2026.113214},
pmid = {42229803},
issn = {1083-351X},
abstract = {The COVID-19 pandemic is often viewed as a once-in-a-century event. However, the rise of new variants and the potential for infections from related coronaviruses continues to be a significant concern. Vaccines were a successful deterrent to COVID-19, but anti-coronavirus drugs to treat individuals with COVID-19 or Long COVID are not robust. Efforts to identify novel coronavirus and host targets for drug therapies are highly valued. We determined that the SARS-CoV-2 Nsp13 helicase resolves G-quadruplexes (G4) of various topologies in an ATP-stimulated manner. Additionally, the requirement for a 5'-single-stranded tail flanking DNA-G4 indicates its 5'-to-3' translocation directionality. G4 ligands were tested for inhibition of Nsp13 G4 resolvase. PhenDC3 inhibited Nsp13 resolution of four-stranded parallel G4 (IC50 = 0.06 nM), 150-fold more potent than two-stranded anti-parallel G4 (IC50 = 9 nM) and 680-fold more potent than the prominent human G4 resolvase FANCJ on the four-stranded parallel substrate (IC50 = 41 nM). Nsp13 is also capable of resolving uni-molecular RNA-G4 substrates, including a SARS-CoV-2-derived RNA-G4-forming sequence, strongly stimulated by its intrinsic ATPase activity. Nsp13-catalyzed resolution of a RNA-G4 substrate is inhibited by the G4 ligand PhenDC3 in a dose-dependent manner. Consistent with the biochemical studies that Nsp13 resolves RNA G-quadruplexes, Nsp13-transfected human cells treated with several G4 ligands displayed reduced RNA-G4 accumulation. The anti-viral regulator Cellular Nucleic Acid Binding Protein (CNBP) interacts with Nsp13 and inhibits Nsp13 G4 resolvase in vitro, suggesting a host mechanism to modulate Nsp13-dependent SARS-CoV-2 replication, which may have implications for G4-based coronavirus therapies.},
}
@article {pmid42231417,
year = {2026},
author = {Yang, J and Rai, KK and Gowman, H and Harrison, C and Gruben, D and Butfield, R and Reynard, C and Hulme, R and Jimenez, I and Volkman, HR and Nguyen, JL},
title = {Characteristics, all-cause healthcare resource utilisation, and costs among high-risk adults with long COVID during Omicron predominance, 2022-2023: a retrospective cohort study using UK primary care data.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14852-0},
pmid = {42231417},
issn = {1472-6963},
abstract = {BACKGROUND: Long COVID, a diverse set of symptoms that persist after a minimum of 4 weeks from the initial SARS-CoV-2 infection, has posed substantial burden to the UK healthcare system. However, little is known about the clinical and economic burden during Omicron predominance, and further, the burden on social care.<br><br>METHODS: A retrospective study was conducted using UK primary care electronic records of adults with confirmed and/or probable acute COVID-19 (index) from The Health Improvement Network between 09/2022 and 05/2023 and eligible for COVID-19 vaccination. Long COVID was identified if patients had&#x2009;&#x2265;&#x2009;1 long COVID signs/symptoms or long COVID diagnostic or referral code&#x2009;&#x2265;&#x2009;4 weeks post-infection. Baseline characteristics, healthcare resource utilisation (HCRU) and costs, and care home admission rates and costs (rates per 100 patient-months (PM) and costs per-patient-per-month (PPPM)), were described in those with long COVID. Outcomes were also stratified by age and COVID-19 vaccine eligibility.<br><br>RESULTS: Of 5,661 eligible patients, 2,772 (49.0%) had long COVID; of these, very few (0.8%; n&#x2009;=&#x2009;23) had a long COVID diagnostic or referral code. Patients with long COVID had high primary and secondary care HCRU: primary care consultation rate of 160.6 per 100 PM; mean primary care consultation cost of &#xa3;82 PPPM; and hospitalisation rate of 7.1 per 100 PM. In stratified analyses, HCRU rates and primary care costs were higher in older age groups than the younger age groups, and separately, among those eligible for two booster doses than those eligible for only one booster dose during the respiratory virus season.<br><br>CONCLUSION: This study highlights the healthcare burden of long COVID during the UK Omicron period, including higher primary care use, hospitalisations, and costs, particularly in older adults and those at high-risk eligible for two boosters, underscoring the need for targeted strategies to address long COVID.},
}
@article {pmid42235362,
year = {2026},
author = {Brodwall, EM and Selvakumar, J and Havdal, LB and Sommen, S and Berven, LL and Cvejic, E and Wyller, VBB and Pedersen, M},
title = {Correlates of fatigue in SARS-CoV-2-positive and -negative adolescents and young adults: Repeated cross-sectional analyses from a prospective cohort study.},
journal = {Journal of psychosomatic research},
volume = {209},
number = {},
pages = {112885},
doi = {10.1016/j.jpsychores.2026.112885},
pmid = {42235362},
issn = {1879-1360},
abstract = {PURPOSE: To investigate cross-sectional associations between concurrent fatigue and a range of covariates in adolescents and young adults with acute SARS-CoV-2 infection and follow-up six months after infection, as well as in SARS-CoV-2-negative controls.<br><br>METHODS: A total of 404 SARS-CoV-2 -positive adolescents and young adults were studied during their infection and again six months post-infection, compared to 105 SARS-CoV-2-negative controls. In this exploratory study, cross-sectional linear regression analyses were conducted at each time point to examine associations between fatigue and a range of covariates, including biomarkers, functional tests, symptoms, and psychological traits.<br><br>RESULTS: Fatigue was significantly and strongly associated with all other symptoms (p&#xa0;<&#xa0;0.001), poor sleep quality (p&#xa0;<&#xa0;0.001), psychological traits and negative emotions (p&#xa0;<&#xa0;0.001), and lower quality of life (p&#xa0;<&#xa0;0.001), across all cohorts. During the early convalescent phase of SARS-CoV-2 infection, fatigue showed few cross-sectional associations with immunological or autonomic markers, whereas such associations were observed six months after infection. COVID-negative controls also displayed immunological associations with fatigue.<br><br>CONCLUSIONS: Fatigue was consistently linked to concurrent symptom burden, insufficient sleep, negative emotions, and reduced quality of life, irrespective of infection status or timing. The lack of immunological and autonomic associations with fatigue during the early convalescent phase of SARS-CoV-2 infection are followed by their presence at six months. Findings suggests that the pattern of correlates may differ over time. These exploratory cross-sectional findings are non-causal and cannot establish directionality but are compatible with neuroscientific models on persistent symptoms and sustained arousal.},
}
@article {pmid42235853,
year = {2026},
author = {Tulling, AJ and Holierhoek, MG and van der Kroft, SN and van Ostaijen-Ten Dam, MM and van Houten, MA and Terheggen-Lagro, SWJ and Lugthart, G and Buddingh, EP},
title = {No expansion of MIS-C associated TCR Vβ 21.3[+] T-cells in pediatric Post-COVID Condition.},
journal = {Immunology letters},
volume = {},
number = {},
pages = {107196},
doi = {10.1016/j.imlet.2026.107196},
pmid = {42235853},
issn = {1879-0542},
abstract = {The etiology of pediatric post-COVID Condition (PPCC; i.e., long-COVID) remains elusive. Another post-infectious complication of SARS-CoV-2 in children is Multisystem Inflammatory Syndrome in Children (MIS-C) in which an expansion of polyclonal TCR Vβ 21.3[+] (TRBV11-2) T-cells has been observed. Flow cytometry was performed in 86 PPCC, 32 MIS-C, 7 pediatric acute COVID-19, and 15 age matched healthy controls. Most children with MIS-C (25/32, 78%) had an enrichment of Vβ21.3[+] expressing cells within activated HLA-DR[+]/Ki67[+] T-cells. In contrast to children with MIS-C, there was no enrichment of Vβ21.3 expressing cells in PPCC patients, arguing against a shared pathophysiology.},
}
@article {pmid42220880,
year = {2026},
author = {Zhang, L and Wang, M and Zhang, H and Mao, G},
title = {SARS-CoV-2 and reproductive system: a scientometric study.},
journal = {Frontiers in reproductive health},
volume = {8},
number = {},
pages = {1844245},
pmid = {42220880},
issn = {2673-3153},
abstract = {OBJECTIVES: Growing evidence, such as Long COVID, suggests that the interaction and underlying mechanism between SARS-CoV-2 and human cells, especially the long-term effect on the reproductive system, remain poorly understood, which should raise high public health concern. This study aimed to enhance understanding of the scientific development status in this field of the viral infection and the human genital system, and to explore key hotspots, thematic trends, major issues through a scientometric analysis of the relevant literature.<br><br>METHODS: This study retrieved the literature (2020-2025) on association between SARS-CoV-2 and the genital system from three databases, Web of Science Core Collection (WOSCC), Scopus, and PubMed, and performed comprehensive scientometric analysis of the literature to explore the bibliometric distribution, thematic trends and the major problems in this area using Bibliometrix/BiblioShiny.<br><br>RESULTS: A total of 2,354 publications from 2020 to 2025 were included in the analysis. The annual production of the publications has shown a declining trend since 2022, and is predicted to reach nearly zero by 2030. The most relevant journal was Mathematical Biosciences and Engineering. Wang X. and Wang Y. were the most prolific authors. China and the USA had the highest production of documents, while Sweden and Portugal had the highest average article citations. The most global cited document was "Cytokine Storm" (Fajgenbaum D, 2020, New Engl J Med). The most frequent keywords were covid-19, human, sars-cov-2, cell proliferation, pandemic, and basic reproduction number. Etiology, antigen presentation and sperm viability have been the newly emerging trend topics since 2025. A thematic map shows that the cluster of the keywords closely related to the impact of SARS-CoV-2 on reproductive system was located in the lower left quadrant, indicating that the themes associated with these keywords appeared early but remain underdeveloped. The USA, China, Italy and Germany conducted the most research collaborations, while most African, Latin American, and Asian countries were rarely involved.<br><br>CONCLUSION: This report provides comprehensive insights, including the latest macroscopic perspectives, references, and practical guidance, for shaping research strategies, managing public health resources, and fostering scientific collaborations, featuring novel viewpoints that merit attention in the field.},
}
@article {pmid42225171,
year = {2026},
author = {Nóbrega Júnior, JC and Brandão, SS and Formiga, MF and Xavier, D and Torres, R and Souza, SN and Fink, JB and Ari, A and Reinaux, C and Brandão, D and Campos, S and Andrade, AD},
title = {Inspiratory Muscle Fatigue and Pulmonary Deposition-Perfusion Imaging Predict Sleep Dysfunction in Long COVID: Evidence From MTC Scintigraphy and FIT Performance Metrics.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108920},
doi = {10.1016/j.rmed.2026.108920},
pmid = {42225171},
issn = {1532-3064},
abstract = {BACKGROUND: Post-COVID-19 syndrome may impair respiratory function, inspiratory muscle performance, and sleep quality; however, the interaction between inspiratory muscle fatigue, regional deposition/perfusion, and sleep disturbances remains unclear.<br><br>OBJECTIVE: To analyze associations between inspiratory muscle fatigue, pulmonary radiopharmaceutical activity, and sleep disturbances in symptomatic and asymptomatic post-COVID-19 individuals.<br><br>METHODS: This cross-sectional study included 33 post-COVID-19 individuals classified as symptomatic (n=23) or asymptomatic (n=10) according to symptom severity. Inspiratory muscle performance was assessed using maximal inspiratory pressure (MIP), sustained maximal inspiratory pressure (SMIP), and the inspiratory fatigue index (FIT) obtained from an incremental respiratory resistance test. Sleep was assessed by actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). Pulmonary aerosol deposition and perfusion were assessed by gamma scintigraphy using [99]&#x1d50;Tc-DTPA and [99]&#x1d50;Tc-MAA, respectively; total radiopharmaceutical activity was quantified for both lungs combined and for the right and left lungs separately.<br><br>RESULTS: Symptomatic individuals had lower MIP (73 [37] vs 114 [22.50] cmH2O), SMIP (502 [222] vs 935.50 [215] PTU), and FIT (22.30 [9.20] vs 46.25 [20.28]; all p<0.001). Total aerosol deposition (327.16 [232.97] vs 618.26 [187.88] Kct) and total lung perfusion (765.66 [269.94] vs 1046.94 [447.41] Kct) were reduced. PSQI (9 [5] vs 6.50 [6]; p=0.006) and ESS (12 [5] vs 4 [4]; p=0.003) were worse. FIT correlated with total aerosol deposition (r=0.93; p<0.001).<br><br>CONCLUSIONS: Long COVID is associated with reduced inspiratory muscle performance, impaired ventilation/perfusion, and worse sleep, supporting FIT and pulmonary scintigraphy as potential functional markers for assessment and rehabilitation monitoring.},
}
@article {pmid42226451,
year = {2026},
author = {Cheetham, NJ and Beattie, A and Comery, AB and Bowyer, V and , and Carpentieri, JD and Steves, CJ},
title = {Socio-Demographic Inequalities in COVID-19 Health Care Access and Experiences in the United Kingdom: Intersectional and Mixed-Methods Analyses of Open and Closed Questions in a Prospective Cohort Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {3},
pages = {e70692},
doi = {10.1111/hex.70692},
pmid = {42226451},
issn = {1369-7625},
support = {//Chronic Disease Research Foundation/ ; COV-LT-0009//National Institute for Health and Care Research/ ; MR/Y003624/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; United Kingdom/epidemiology ; *COVID-19/epidemiology/therapy ; Female ; *Health Services Accessibility/statistics &amp; numerical data ; Male ; Prospective Studies ; Middle Aged ; Socioeconomic Disparities in Health ; *Healthcare Disparities/statistics &amp; numerical data ; Adult ; Socioeconomic Factors ; Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Access to Primary Care ; },
abstract = {INTRODUCTION: Inequalities in health care access and experiences during the COVID-19 pandemic have been observed along axes of social advantage. It is less well understood how access to care varied intersectionally with combinations of multiple social factors, and how social advantage shaped care experiences for COVID-19 illness.<br><br>METHODS: We analysed responses to both closed (N&#x2009;=&#x2009;3516) and open (N&#x2009;=&#x2009;335) survey questions relating to health and social care access and experiences during the first two and a half years of the COVID-19 pandemic in the United Kingdom community-based cohort, COVID Symptom Study Biobank. Causal effects of individual socio-demographic variables on access to health and social care were estimated with multivariable regression models, weighted for inverse probability of survey completion and adjusted for potential confounders. Associations between care access issues and social strata comprising combinations of sex, education level and local area deprivation were estimated using the intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) approach. Responses to open questions on health care experiences for COVID-19 illness were deductively coded and quantitatively analysed to estimate associations between socio-demographic advantage and various aspects of care experiences.<br><br>RESULTS: Gradients in health and social care access along the lines of social advantage were observed in intersectional MAIHDA models, with the predicted probability of access issues highest for the stratum comprising female participants with lowest education and highest deprivation levels (42.9%, 95% CI: 31.9%-54.6%), and lowest for male participants with highest education and lowest deprivation (18.7%, 95% CI: 12.8%-26.7%). Socially disadvantaged participants also reported receiving poorer care for COVID-19, with lower likelihood of reporting receiving adequate care and specialist care for long COVID, and higher likelihood of negative experiences of care versus advantaged participants.<br><br>CONCLUSIONS: Inequalities in likelihood of health and social care access issues were observed, as well as inequalities in care experiences specifically for COVID-19, with issues accessing care and poorer experiences more likely to be reported by individuals with greater social disadvantage.},
}
@article {pmid42227474,
year = {2026},
author = {Yang, F and Zhu, Z and Wang, Y and Qin, Y and Yue, H},
title = {Lung-Brain Axis Mechanisms of Cognitive Dysfunction in Long COVID.},
journal = {CNS &amp; neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273421593251202095722},
pmid = {42227474},
issn = {1996-3181},
abstract = {Cognitive dysfunction, characterized by memory impairment, attentional deficits, and executive dysfunction, represents a critical clinical manifestation in post-acute sequelae of COVID-19 that significantly compromises patients' quality of life. The lung-brain axis, as a bidirectional regulatory network connecting the respiratory system to the central nervous system, interacts through neural circuits, humoral pathways, and microbial pathways, and may play a central role in the cognitive impairments occurring in long COVID (LC). This paper systematically reviews the multidimensional pathways of the lung-brain axis and their pathological mechanisms in the cognitive impairment of LC, including direct viral neuroinvasion during the acute phase, chronic injury triggered by viral persistence, immune homeostasis dysregulation, hypoxaemia, microbiome disruption, and renin- angiotensin system imbalance. It then explores clinical intervention strategies based on the lungbrain axis, integrating supportive treatments, such as oxygen therapy, exercise therapy, and cognitive training, with treatments targeting the lung-brain axis, including antiviral drugs, immunomodulation, probiotics, and neuromodulation techniques. It is also suggested that future research should favour the integration of multi-omics technologies and the development of individualised therapeutic targets.},
}
@article {pmid42227945,
year = {2026},
author = {Degenhardt, BF and Rehman, Y and Luebbering, C and Divine, WH and Jackson, M},
title = {Role of osteopathic manipulative treatment in the management of persistent post-COVID-19 symptoms and functional outcomes: study protocol of a prospective pilot study.},
journal = {Journal of osteopathic medicine},
volume = {},
number = {},
pages = {},
pmid = {42227945},
issn = {2702-3648},
abstract = {CONTEXT: The postacute sequelae of SARS-CoV-2 (PASC) are unexpected consequences of COVID-19 infections. Many patients continue to have PASC-related symptoms weeks to months after an infection, experiencing morbidity that affects daily living. Historically, many symptoms associated with PASC have been responsive to osteopathic manipulative medicine (OMM).<br><br>OBJECTIVES: To develop and disseminate a standardized clinical protocol for evaluating the efficacy of osteopathic manipulative treatment (OMT) in managing PASC. This study will assess OMT's impact on symptoms and functional outcomes while systematically monitoring for adverse events (AEs) within this patient population.<br><br>METHODS: The protocol is a prospective, single-arm, pre-post treatment cohort study involving patients seeking OMT with PASC-related symptoms. Standardized outcome measures have been selected to assess PASC-related symptoms and lifestyle impact over a 6-month longitudinal period. Data collection will occur at enrollment (baseline), at every second OMT session, and at a final follow-up. This final assessment will be conducted either 6&#xa0;months postenrollment or 2&#xa0;months after the cessation of treatment, whichever occurs first. Pragmatic, personalized OMT based on the physicians' clinical findings and judgment is recommended to provide a realistic assessment of real-world OMT practice vs. a protocol-based intervention. The design developers recommend utilizing a web-based, HIPAA-compliant platform such as Research Electronic Data Capture (REDCap) to facilitate informed consent procedures, disperse and collect surveys, provide reminders for completing surveys, and store and manage&#xa0;data.<br><br>RESULTS: At baseline, participants will provide demographic and clinical data, including age, sex, race, smoking and employment status, pre-COVID-19 health status, and comorbidities. We will also document symptoms and treatments associated with their acute COVID-19 illness. Descriptive statistics will summarize baseline characteristics. Longitudinal outcomes&#xa0;-&#xa0;encompassing neurocognitive function, physical symptoms, quality of life, and work status&#xa0;-&#xa0;will be analyzed utilizing generalized linear mixed models (GLMMs). This approach accounts for clinician-level clustering and adjusts for potential confounding variables while monitoring for adverse effects.<br><br>CONCLUSIONS: This protocol provides a standardized, pragmatic framework to evaluate the impact of OMT on the multifaceted symptoms of PASC. By utilizing a longitudinal, real-world design and robust statistical modeling (GLMM), the study aims to establish evidence-based insights into how osteopathic intervention can improve functional outcomes and quality of life for PASC patients. Furthermore, this standardized approach facilitates multi-site collaboration, ensuring that findings are reproducible and scalable within the broader medical community.},
}
@article {pmid42216347,
year = {2026},
author = {Faseeh, A and Rida, M and Karim, NE and Zafar, A and Shah, A and Perveen, A},
title = {Prevalence and long-term outcomes of brain fog and cognitive impairment in individuals with long COVID: A systematic review.},
journal = {Medicine},
volume = {105},
number = {22},
pages = {e49022},
doi = {10.1097/MD.0000000000049022},
pmid = {42216347},
issn = {1536-5964},
mesh = {Humans ; *Cognitive Dysfunction/epidemiology/etiology ; Prevalence ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Female ; Male ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID is increasingly recognized as a complex multisystem condition, with brain fog and cognitive impairment emerging as some of its manifestations. Despite growing literature, the pooled prevalence, subgroup differences, and underlying mechanisms remain incompletely understood.<br><br>METHODS: We systematically reviewed 47 studies (2000-2025) encompassing over 25,000 patients to evaluate the prevalence of brain fog and cognitive impairment among long COVID populations. Data were extracted on study design, patient demographics, follow-up duration, and subgroup variables including gender, hospitalization, vaccination, and geographic region. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS v9.0) and JBI checklists. Quantitative synthesis was performed with subgroup and temporal analyses, presented in forest plots and summary figures.<br><br>RESULTS: The pooled prevalence of brain fog was 30% (95% CI: 28-32), while cognitive impairment was 25% (95% CI: 23-27). Female patients consistently showed higher rates compared to males (34% vs 23% for brain fog; 29% vs 21% for cognitive impairment). Community-managed patients demonstrated higher prevalence compared to hospitalized cohorts, and unvaccinated individuals had a greater burden than vaccinated ones. Temporal analyses indicated that prevalence increased with longer follow-up, suggesting symptom persistence or late manifestation. Pathophysiological explanations include neuroinflammation, microvascular injury, immune dysregulation, and psychosocial stressors.<br><br>CONCLUSION: Brain fog and cognitive impairment are common, persistent, and clinically significant features of long COVID. Gender differences, vaccination status, and follow-up duration influence prevalence. Future studies should focus on mechanisms, preventive strategies, and targeted interventions to mitigate long-term cognitive sequelae.},
}
@article {pmid42218573,
year = {2026},
author = {Ferreira, AMS and Ferreira, FELL and do Nascimento, JA and de Carvalho, ALB and Alverga, CCF and Pernambuco, L},
title = {Health-Related Quality of Life of Adults With Long COVID: A Cross-Sectional Study in Primary Care.},
journal = {Journal of clinical nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jocn.70383},
pmid = {42218573},
issn = {1365-2702},
support = {47449.673.29754.11082021//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Estado da Para&#xed;ba/ ; //Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; },
abstract = {AIMS: To evaluate the health-related quality of life (HRQOL) of adults with Long COVID 2 years and beyond after COVID-19 illness.<br><br>DESIGN: Cross-sectional study.<br><br>METHODS: Health status was assessed using the EQ-5D-5L instrument among 226 adults diagnosed in primary care with mild-to-moderate COVID-19 during the 2021 pandemic. Data were collected through a cross-sectional survey using a standardized questionnaire with a set of validated clinical outcomes for Long COVID. The sample consisted of adults aged &#x2265;&#x2009;18&#x2009;years who attended the specified ambulatory settings, tested positive for SARS-CoV-2, and agreed to be interviewed; the response rate was 70%. Health utility scores were compared between adults with and without Long COVID. Multivariate logistic regressions were applied to investigate the relationship between Long COVID and health-related quality of life outcomes.<br><br>DATA SOURCES: Primary data were collected from six public Family Health Care Units in Jo&#xe3;o Pessoa, Brazil, between May 2023 and July 2024.<br><br>RESULTS: Adults with Long COVID had statistically significantly lower median utility scores (0.784, IQR: 0.633-0.902) than those without persistent symptoms (1.0, IQR: 0.877-1.0). Poorer HRQOL was more evident among women, older adults, non-White individuals, participants with pre-existing chronic diseases, and those with lower educational attainment. Long COVID was associated with impairments in anxiety/depression, pain/discomfort and usual activities.<br><br>CONCLUSION: Adults with Long COVID experienced poorer HRQOL 2&#x2009;years or longer after mild-to-moderate infection compared with those without persistent symptoms, regardless of sex, age, ethnicity, education level or comorbidities. These findings support the implementation of targeted interventions and rehabilitation services in primary care for individuals experiencing long-term health problems following COVID-19 illness.<br><br>Identifying adults at greater risk of persistent health impairments following COVID-19 may help health professionals, caregivers and policymakers better address the aspects of patients' lives that lack quality and develop a multidisciplinary approach in primary care to managing this condition.<br><br>IMPACT: What problem did the study address? &#x25cb; This study examined the association between persistent symptoms 2&#x2009;years or longer after non-severe COVID-19 illness and health-related quality of life. What were the main findings? &#x25cb; Long COVID was associated with poorer health-related quality of life, particularly in the domains of anxiety/depression, pain/discomfort and usual activities. Where and on whom will the research have an impact? &#x25cb; The findings highlight the need for multidisciplinary management of long-term health problems among adult COVID-19 survivors in primary care.<br><br>REPORTING METHODS: The STROBE checklist was followed.<br><br>No patient or public contribution.},
}
@article {pmid42219699,
year = {2026},
author = {Gong, S and Liu, Y and Huang, B and Chan, NY and Partinen, E and Benedict, C and Bjorvatn, B and Merikanto, I and De Gennaro, L and Dauvilliers, Y and Holzinger, B and Yordanova, J and Korman, M and Reis, C and Landtblom, AM and Mota-Rolim, S and Nadorff, MR and Chung, F and Inoue, Y and Hrubos-Strøm, H and Matsui, K and Bolstad, CJ and Xue, P and Espie, CA and Morin, CM and Penzel, T and Plazzi, G and Partinen, M and Wing, YK},
title = {Association of Prodromal Parkinson's Disease-Like Features in Long COVID With Dream-Enactment Behaviours.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e70371},
doi = {10.1111/jsr.70371},
pmid = {42219699},
issn = {1365-2869},
abstract = {Emerging evidence links COVID-19 to the predisposition of Parkinson's disease (PD). However, the relationship between long COVID and prodromal PD-like features remains unclear, particularly in long COVID participants with dream-enactment behaviours (DEBs) that may be suggestive of possible REM sleep behaviour disorder. This study aimed to quantify the burden of prodromal PD-like features in long COVID. This online survey (May-Nov 2021) across 16 countries/regions included 11,261 participants. Data on demographics, COVID-19 diagnosis, long COVID symptoms, sleep features and other typical prodromal PD-like features were collected. The likelihood ratio (LR) of prodromal PD was calculated as a proxy for each participant's overall burden of prodromal PD-like features, based on the 2019 Movement Disorder Society research criteria. Participants with long COVID (n = 1155) exhibited more symptoms suggestive of prodromal PD-like features, including DEBs, olfactory dysfunctions, constipation, excessive daytime sleepiness, postural dizziness, depression with/without anxiety, urinary dysfunctions, cognitive impairment and a higher LR of prodromal PD when compared to non-COVID-19 participants and COVID-19 recoverees. Long COVID was associated with a 73% higher burden of potential prodromal PD-like features (adjusted odds ratio [aOR] = 1.73, 95% confidence interval [CI] = 1.57-1.90). Among those with long COVID, emergence or exacerbation of post-infection DEBs further increased this burden by 38% (aOR = 1.38, 95% CI = 1.19-1.60). Our study suggested that long COVID is associated with an increased burden of prodromal PD-like features, which appears to be further enhanced with DEBs.},
}
@article {pmid42220539,
year = {2026},
author = {Hai, Z and Yang, W and Ghazi, A and Buitrago, A and Marín-García, P and Azcárate, IG and González-Escalada, A and Rossi, N and Benítez-Cruz, J and Estévez-Benito, I and Tortajada, A and Regueiro, JR and Bautista, JM and Martinez-Quiles, N},
title = {Increased anti-nucleocapsid secretory IgA and consumption of complement component 3 in post-COVID syndrome patients.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1822171},
pmid = {42220539},
issn = {1664-3224},
mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/immunology ; *Complement C3/immunology/metabolism ; *SARS-CoV-2/immunology ; Adult ; Post-Acute COVID-19 Syndrome ; *Immunoglobulin A, Secretory/immunology ; Saliva/immunology ; *Antibodies, Viral/immunology/blood ; Aged ; *Coronavirus Nucleocapsid Proteins/immunology ; },
abstract = {INTRODUCTION: Post-COVID syndrome represents a major global health challenge which is characterized by immune dysregulation, although many aspects of the immune response remain incompletely understood, particularly the antibody response and the role of the complement system. We previously studied a post-COVID syndrome cohort in comparison to a COVID-recovered control cohort from Comunidad de Madrid (Spain) and found that post-COVID syndrome patients exhibited readily detectable serum anti-Nucleocapsid antibodies while showing deficient antibody production against the full-length Spike, despite maintaining a well-preserved anti-receptor binding domain (RBD) response.<br><br>METHODS: In the present study, we quantified anti-Nucleocapsid secretory immunoglobulin A (sIgA) in saliva and analyzed selected key components of the complement system, including C3, C4, factor B (FB), factor H (FH), and total hemolytic activity (CH50). Additionally, we quantified circulating immune complexes. We conducted general, stratified, correlation, and regression analyses.<br><br>RESULTS: Anti-Nucleocapsid sIgA was increased in post-COVID syndrome samples compared with COVID-recovered controls. Although CH50 levels were similar, we detected a reduced concentration of C3. The levels of C4 were decreased but not significantly. Interestingly, in recently reinfected fully vaccinated patients, serum anti-Nucleocapsid IgG showed a negative correlation with FH and CH50. No differences were found for the concentration of circulating immune complexes. Regression analysis indicated that C3 levels can discriminate patients from controls efficiently, and combining anti- Nucleocapsid sIgA and C3 levels yielded improved discriminatory power.<br><br>DISCUSSION: The elevated anti-Nucleocapsid sIgA levels found did not correlate with increased anti-Nucleocapsid IgG in serum, as expected from their different temporal dynamics. The reduced C3 levels may reflect ongoing complement activation and subsequent consumption, which might be potentiated by increments in serum of anti-Nucleocapsid antibodies produced after reinfections. In conclusion, our findings suggest that salivary anti-Nucleocapsid IgA and C3 consumption, which seems to be more subtle parameter than CH50, may serve as candidate biomarkers of post-COVID syndrome, requiring validation in independent cohorts. Furthermore, these results implicate the complement system as a key dysregulated component of the immune response contributing to the pathophysiology of post-COVID syndrome, thus potentially amenable to targeted therapies.},
}
@article {pmid42215921,
year = {2026},
author = {Rocha, JQS and Dos Santos Camilo, L and Duro, SMS and de Oliveira Saes, M},
title = {Bidirectional relationship between depression and long COVID symptoms: findings from the Sulcovid-19 longitudinal survey.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-27755-w},
pmid = {42215921},
issn = {1471-2458},
support = {21/2551-0000107-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado do Rio Grande do Sul/ ; },
abstract = {Long COVID is a condition that may manifest after SARS-CoV-2 infection, associated with complications such as depression and persistent symptoms. This study evaluated the relationship between prior depression and the occurrence of Long COVID, as well as investigated whether symptoms of this condition increase the risk of depression following infection in adults from southern Brazil. Using data from the longitudinal Sulcovid-19 study, the analysis included variables such as sex, age, skin color, marital status, income, smoking, body mass index, comorbidities, and hospitalization. The prevalence of Long COVID was 60 percentage points higher among individuals with prior depression, and this condition increased the probability of depression after infection by 65%. Associations were evaluated using Poisson regression in Stata 17.0. The results highlight the importance of investigating the implications of Long COVID and developing effective therapeutic approaches.},
}
@article {pmid42215824,
year = {2026},
author = {Wang, K and Zhang, Y and Zhao, H and Zhao, T},
title = {Temporal patterns of neurological deterioration in COVID-19 survivors: a longitudinal cohort analysis of post-acute neurological sequelae.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {6},
pages = {},
pmid = {42215824},
issn = {1590-3478},
mesh = {Humans ; Female ; Middle Aged ; Longitudinal Studies ; *COVID-19/complications/physiopathology ; Male ; Retrospective Studies ; Survivors ; Post-Acute COVID-19 Syndrome ; Aged ; *Cognitive Dysfunction/etiology/epidemiology/physiopathology ; Adult ; Nerve Conduction Studies ; *Peripheral Nervous System Diseases/etiology/epidemiology/physiopathology ; Autonomic Nervous System Diseases/etiology/physiopathology ; *Nervous System Diseases/etiology ; },
abstract = {BACKGROUND: Post-acute neurological sequelae of COVID-19 represent a significant clinical challenge. The temporal evolution and predictive factors remain incompletely characterized.<br><br>METHODS: We conducted a retrospective longitudinal cohort study of 386 COVID-19 survivors with assessments at baseline and 3, 6, 12, and 24 months. Primary outcomes included cognitive function (Montreal Cognitive Assessment [MoCA]), peripheral nerve function (nerve conduction studies [NCS]), and autonomic function (Composite Autonomic Symptom Score-31 [COMPASS-31]).<br><br>RESULTS: Among 386 participants (mean age 51.92&#xb1;14.86 years; 53.9% female), cognitive impairment prevalence decreased from 67.6% at baseline to 43.4% at 24 months (P<0.001). Mean MoCA scores improved from 24.61&#xb1;2.12 to 25.84&#xb1;2.31. Autonomic dysfunction demonstrated a biphasic pattern with worsening at 6 months (COMPASS-31: 38.49&#xb1;22.13 vs. 32.81&#xb1;19.11 at 3 months). Peripheral neuropathy remained stable (42.5% to 45.0%). Independent predictors of persistent cognitive impairment included ICU admission (adjusted odds ratio [aOR] 2.84; 95% CI 1.52-5.31), age &#x2265;65 years (aOR 1.95; 95% CI 1.18-3.22), and depression history (aOR 1.92; 95% CI 1.08-3.41).<br><br>CONCLUSIONS: Neurological sequelae following COVID-19 demonstrate domain-specific recovery trajectories. Cognitive function improves gradually, autonomic dysfunction exhibits a biphasic pattern, and peripheral neuropathy persists. These findings support targeted, domain-specific rehabilitation strategies.},
}
@article {pmid42205482,
year = {2026},
author = {Albelasi, A},
title = {Symptoms, mechanisms, and management of long COVID: understanding its prevalence, characteristics, and healthcare challenges in Saudi Arabia.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1747443},
pmid = {42205482},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/epidemiology/therapy ; Saudi Arabia/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; SARS-CoV-2 ; Pandemics ; },
abstract = {Long COVID is a prolonged health condition wherein patients continue to experience symptoms long after recovering from infection, so it presents a significant global health challenge with multi-organ involvement. This review provides evidence from several studies to elucidate the prevalence, symptom clusters, and underlying mechanisms of Long COVID. Key findings highlight fatigue (25-73%), cognitive dysfunction, respiratory symptoms (dyspnea: 6.9-47%), cardiovascular symptoms (49.37/1,000), and reproductive symptoms (menstrual irregularities, erectile dysfunction) as predominant manifestations. Mechanistic insights include viral persistence, immune dysregulation, and endothelial dysfunction. The review gives detailed information about prevalence and immunological studies carried out in Saudi Arabia on Long COVID and underscores the importance of longitudinal immune studies, multidisciplinary approaches, biobanks, and global collaborations to improve patient outcomes. Recommendations emphasize tailored therapies, psychological support, and large-scale cohort studies to address heterogeneity and optimize care for Long COVID patients in Saudi Arabia.},
}
@article {pmid42205736,
year = {2026},
author = {Zhang, GY and Lin, JC and Nguyen, D and Khatana, SAM and Giordano, TP},
title = {Long COVID and Cardiovascular Diseases Among U.S. Adults: Results From the U.S. Medical Expenditure Panel Survey.},
journal = {Clinical Medicine Insights. Cardiology},
volume = {20},
number = {},
pages = {11795468261455387},
pmid = {42205736},
issn = {1179-5468},
abstract = {OBJECTIVE: Long COVID is associated with persistent symptoms including cardiovascular complications; however, the epidemiology and directionality of this association remain unclear.<br><br>METHODS: Utilizing a retrospective cohort study design with cross-sectional analyses, 8,332 respondents aged 18 and older from the 2022 Medical Expenditure Panel Survey (MEPS) who had a prior COVID-19 infection, were analyzed to determine the temporal association between long COVID and cardiovascular disease (CVD), modeling each as both outcome and exposure in separate analyses.<br><br>RESULTS: Long COVID was associated with any CVD diagnosis (OR 1.37; 95% CI: 1.05-1.80), specifically angina (OR 1.81; 95% CI: 1.18-2.77) and myocardial infarction (OR 1.50; 95% CI: 1.01-2.23). Temporally, long COVID was associated with higher odds of CVD diagnoses in the same year or following year after COVID-19 (OR 2.62; 95% CI: 1.05-6.51) and in subsequent years only (OR 8.60; 95% CI: 1.53-48.3). Respondents with pre-existing CVD did not have statistically significant greater odds of reporting new long COVID symptoms.<br><br>CONCLUSION: Our findings demonstrate that long COVID is associated with the subsequent development of CVD, underscoring the need for further research in this patient population to improve health interventions.},
}
@article {pmid42208496,
year = {2026},
author = {Wall, EC and Richter, AG},
title = {Autoantibodies in long COVID: A mechanistic foothold in a heterogeneous disease.},
journal = {Cell},
volume = {189},
number = {11},
pages = {3179-3180},
doi = {10.1016/j.cell.2026.04.044},
pmid = {42208496},
issn = {1097-4172},
mesh = {Humans ; *COVID-19/immunology/pathology/complications ; Post-Acute COVID-19 Syndrome ; *Autoantibodies/immunology ; SARS-CoV-2/immunology ; },
abstract = {Long COVID is a heterogeneous, multi-system disease that poses challenges for patients, health systems, and economies. Two papers in Cell and Cell Reports Medicine from independent groups suggest that autoantibodies in a subset of long COVID patients can directly drive symptoms such as pain, fatigue, or neurocognitive problems.},
}
@article {pmid42208499,
year = {2026},
author = {de Sá, KSG and Silva, J and Bayarri-Olmos, R and Baker, CA and Lu, Z and Gipson, W and Na, D and Chen, B and Wenxue, L and Khosroabadi, D and Brinda, R and Constable, RAR and Omene, B and Colom Díaz, PA and Kwon, DI and Rodrigues, G and Heidecke, H and Schulze-Forster, K and Gross, A and Shneer, T and Clarke, A and Linnekin, T and Brate, A and Brown, L and Buda, H and Jatiani, S and Moise, L and Greene, K and Bhagchandani, S and Bhattacharjee, B and Gehlhausen, J and Wood, J and Tabacof, L and Scheibenbogen, C and Liu, Y and Guan, L and Schneeberger Pane, M and Putrino, D and Horvath, TL and Iwasaki, A},
title = {A causal link between autoantibodies and neurological symptoms in long COVID.},
journal = {Cell},
volume = {189},
number = {11},
pages = {3214-3235.e37},
doi = {10.1016/j.cell.2026.04.042},
pmid = {42208499},
issn = {1097-4172},
mesh = {Humans ; *Autoantibodies/immunology ; Animals ; *COVID-19/immunology/complications ; Post-Acute COVID-19 Syndrome ; Mice ; SARS-CoV-2 ; Immunoglobulin G/immunology ; Female ; Male ; Middle Aged ; Post-Infectious Disorders ; *Nervous System Diseases/immunology ; },
abstract = {Acute SARS-CoV-2 infection triggers the de novo production of diverse, functional autoantibodies (AABs) that remain elevated in long COVID (LC), but their pathogenic role remains unclear. Using tissue-based immunofluorescence, ELISA, human protein array, and mass spectrometry assays, we identified a broad range of AAB targets among individuals with LC. Individuals with neurocognitive symptoms showed increased AABs against central nervous system (CNS) and peripheral nervous system proteins. Purified immunoglobulin G (IgG) reacted with human locus coeruleus, thalamus, adrenal gland, and thyroid and cross-reacted with mouse sciatic nerve and meninges. CNS-reactive AABs correlated with several neurological symptoms. MED20-targeting IgG from patients with LC showed enhanced antibody-dependent phagocytosis. Passive transfer of IgG from individuals with LC into mice induced fatigue-like behavior, loss of balance/coordination, thermal hyperalgesia, small fiber nerve damage, and increased pain-related neuronal activity, recapitulating patients' symptoms. These findings suggest that targeting AABs might offer therapeutic benefits for this LC subgroup.},
}
@article {pmid42208931,
year = {2026},
author = {Brunvoll, SH and Fagerland, MW and Nygaard, AB and Ellingjord-Dale, M and Istre, MS and Landrø, NI and Bø, R and Holland, P and Kalleberg, KT and Dahl, JA and Søraas, A},
title = {Long COVID symptoms before and 3-35 Months after SARS-CoV-2 infection in a Norwegian prospective cohort study, symptoms over the pandemic and different virus variants.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108822},
doi = {10.1016/j.ijid.2026.108822},
pmid = {42208931},
issn = {1878-3511},
abstract = {OBJECTIVES: Examine long COVID symptoms, prevalence of symptoms over the pandemic, and compare symptoms due to the Omicron variants with symptoms due to earlier variants of the SARS-CoV-2 virus.<br><br>METHODS: In the present Norwegian prospective cohort study 115737 persons, 18-96 years, completed 1-6 questionnaires 3-35 months after a positive and/or negative SARS-CoV-2 test between 2020-2023.<br><br>RESULTS: The following symptoms were reported more frequently 3-35 months after than before positive SARS-CoV-2 test (n=37400): worsening of health, (OR 1.79 [CI 1.71-1.86]), memory problems (2.21 [2.06-2.37]), concentration problems (1.98 [1.87-2.09]), dyspnea (1.95 [1.84-2.07]), fatigue (1.46 [1.41-1.52]) and smell/taste changes (3.12 [2.84-3.42]). The prevalence of symptoms was lower at the end of 2022 than in 2020. A positive SARS-CoV-2 test during the Omicron-dominated period was associated with lower prevalence of symptoms than a positive test during the period dominated by earlier variants.<br><br>CONCLUSIONS: Several symptoms lingered up to 35 months post-SARS-CoV-2 infection. The prevalence of symptoms decreased over the course of the pandemic and were reported less often in those infected with later SARS-CoV-2 variants than earlier variants. The indications of long-term persisting symptoms after COVID-19 and the consequences of new variants should be further monitored.},
}
@article {pmid42212121,
year = {2026},
author = {Holmqvist, M and Sjöström, DJ and Carlson, K and Gullstrand, B and Bengtsson, AA and Kahn, R and Mollnes, TE and Åkesson, P and Nilsson, PH and Kahn, F},
title = {Complement activation in patients with post-acute sequelae after SARS-CoV-2 infection.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1779393},
pmid = {42212121},
issn = {1664-3224},
mesh = {Humans ; *Complement Activation/immunology ; *COVID-19/immunology/complications ; Post-Acute COVID-19 Syndrome ; Female ; *SARS-CoV-2/immunology ; Middle Aged ; Male ; Aged ; Adult ; Biomarkers/blood ; Complement C3b/immunology ; },
abstract = {INTRODUCTION: Post-acute sequelae of SARS-CoV-2 (PASC) may develop after SARS-CoV-2 infection and cause a wide range of symptoms that can persist for years. Several pathophysiological mechanisms have been proposed, including dysregulation of the complement system.<br><br>METHODS: In this study, we analysed markers of complement activation in a cohort of patients with PASC, up to 33 months after the initial infection. We measured the complement activation markers C3bc, C3bBbP and TCC in 38 PASC patients with an initial mild COVID-19 infection, 10 PASC patients with an initial severe COVID-19 infection and 80 control subjects who had recovered completely after a COVID-19 infection.<br><br>RESULTS: Although the patients with an acute mild SARS-CoV-2 infection had a trend towards more severe PASC, we could not find any significant differences in complement activation markers between these patients and controls.<br><br>CONCLUSION: We could not find convincing evidence of activation of the complement system in PASC patients.},
}
@article {pmid42214072,
year = {2026},
author = {Aboagye, NY and Baker, MR and Baker, K and Del Din, S},
title = {Wearable- and Mobile App-Based Activity Pacing and Fatigue Management in Post-COVID-19 Condition: Exploratory Observational Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e91829},
doi = {10.2196/91829},
pmid = {42214072},
issn = {2561-326X},
mesh = {Humans ; *Fatigue/therapy/etiology ; Female ; *Mobile Applications ; Male ; Middle Aged ; *COVID-19/complications ; *Wearable Electronic Devices ; Post-Acute COVID-19 Syndrome ; Adult ; },
abstract = {BACKGROUND: Post-COVID-19 fatigue affects millions worldwide; yet, evidence-based management strategies remain limited. Activity pacing, regulating activity to match available energy and minimize symptom exacerbation, may support symptom management, although optimal pacing approaches remain unclear.<br><br>OBJECTIVE: This study aimed to explore associations between activity pacing strategies delivered through a mobile app and daily fatigue levels in individuals with post-COVID-19 fatigue.<br><br>METHODS: In this exploratory observational study, 19 adults with post-COVID-19 fatigue used wearable devices (Fitbit Inspire 3) for objective activity monitoring and a mobile app (FatigueSense) to self-report daily symptoms (fatigue and energy levels) and optionally select activity pacing goals (light, balanced, or active) over a period of 3 months. We examined associations between pacing strategies and symptom outcomes by using mixed-effects linear models with random intercepts. Same-day outcomes (fatigue and energy reported on the day of goal selection) were analyzed controlling for age and sex. Next-day outcomes (fatigue and energy reported the day following goal selection) were analyzed controlling for age, sex, and prior-day symptoms.<br><br>RESULTS: Across 2182 observation days, participants self-selected pacing goals on 816 (37.4%) days, demonstrating symptom-responsive behavior with higher baseline fatigue on pacing days (mean score 1.74, SD 0.59 vs 1.58, SD 0.54 on nonpacing days on a 0-3 scale where 0="none" and 3="severe"; P=.004). On pacing days (584/816, 71.6% with complete data from 18 participants), active pacing was associated with reduced same-day fatigue (&#x3b2;=-0.34, 95% CI -0.49 to -0.19; P<.001) and increased same-day energy (&#x3b2;=8.8, 95% CI 4.7-12.9; P<.001) compared to light pacing. Balanced pacing also showed significant reductions in fatigue (&#x3b2;=-0.15; P=.008) and increases in energy (&#x3b2;=5.8; P<.001) compared to light pacing. Next-day effects were attenuated and nonsignificant (fatigue: &#x3b2;=-0.05, P=.53; energy: &#x3b2;=1.1, P=.61). Individual heterogeneity was substantial, with an intraclass correlation coefficient of 0.32, indicating that 32% of the variance was attributable to between-person differences. Among participants trying multiple strategies, 58.3% (7/12) showed meaningful responses (&#x2265;0.3-point fatigue reduction) to structured pacing strategies.<br><br>CONCLUSIONS: Structured activity pacing strategies (active and balanced) were associated with improved same-day symptom management in individuals with post-COVID-19 fatigue. However, substantial confounding by indication (self-selection of pacing based on symptom state) and individual heterogeneity limit causal interpretation. These exploratory findings warrant testing in randomized controlled trials to establish efficacy and identify responder characteristics.},
}
@article {pmid42215147,
year = {2026},
author = {Petropoulou, D and Karampela, I and Christodoulatos, GS and Kounatidis, D and Vallianou, NG and Dalamaga, M},
title = {Hormonal, metabolic and metabolomic biomarkers in long COVID.},
journal = {Advances in clinical chemistry},
volume = {133},
number = {},
pages = {217-283},
doi = {10.1016/bs.acc.2026.01.002},
pmid = {42215147},
issn = {2162-9471},
mesh = {Humans ; Biomarkers/metabolism/blood ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism/complications ; *Hormones/metabolism ; Metabolomics ; SARS-CoV-2 ; },
abstract = {Long COVID (LC), a complex syndrome affecting approximately 6-12 % of individuals post infection, is characterized by persistent, fluctuating, or progressive symptoms lasting at least three months. Its pathogenic mechanisms involve viral persistence, chronic inflammation, immune dysregulation, endothelial dysfunction, and endocrine/metabolic abnormalities. Currently, no specific diagnostic tests exist for LC, highlighting the need for reliable biomarkers. This review synthesizes current evidence on hormonal, metabolic, and metabolite biomarkers in LC. While vitamin D deficiency is prevalent in LC, being associated with neurocognitive symptoms, delayed recovery and poor physical performance, particularly in older adults, its lack of specificity reduces diagnostic utility. Insulin resistance markers consistently correlate with fatigue, mood disturbances, and myalgia, suggesting a distinct metabolic LC phenotype. Lower cortisol frequently correlates with fatigue, sensory disturbances, and neurocognitive symptoms. Alterations in cortisol/adrenocorticotropic hormone, growth hormone, prolactin, and gonadotropins suggest a potential hypothalamic-pituitary axis involvement; however, these abnormalities are often transient, dynamic or nonsignificant. While some patients may exhibit low free triiodothyronine associated with fatigue, no significant incidence of thyroid dysfunction and autoimmunity was associated with LC. Despite the absence of a distinct and consistent metabolomic signature, LC is characterized by the activation of the kynurenine pathway, including increased kynurenine and quinolinic acid, being associated with fatigue, neurocognitive and depressive symptoms. Emerging metabolites of mitochondrial dysfunction and lipid metabolism alterations require further validation. Despite promising findings, evidence remains scattered, hindered by small sample sizes and methodological limitations. Future research should prioritize standardization of biomarker assessment, validation in diverse populations, and exploration of targeted therapeutic interventions.},
}
@article {pmid42215664,
year = {2026},
author = {Holingue, C and Villatoro, C and Jacobson, LA and Malone, LA},
title = {Experiences of stigma in children with long COVID.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {42215664},
issn = {1530-0447},
abstract = {OBJECTIVE: This study examined stigma experiences among children and adolescents with Long COVID, a chronic condition marked by persistent symptoms following SARS-CoV-2 infection. We sought to characterize the nature, prevalence, and impacts of stigma on affected youth using a mixed-methods approach.<br><br>METHODS: A cross-sectional survey was administered to 58 caregivers of children seen at a pediatric post-COVID clinic, including the PROMIS&#xae; Parent Proxy Global Health 7&#x2009;+&#x2009;2 measure and nine adapted items from the Internalized Stigma of Mental Illness Inventory. Additionally, 18 parents participated in qualitative interviews analyzed using inductive thematic analysis.<br><br>RESULTS: Stigma was widespread: over 65% of caregivers reported their child felt out of place, and nearly half reported feelings of inferiority or shame. Lower PROMIS Total T scores, reflecting worse caregiver-perceived child health, were significantly associated with experiences of alienation, discrimination, and stigma resistance. Qualitative findings identified three themes: healthcare discrimination, distrust and skepticism, and alienation and isolation, contributing to social withdrawal, emotional distress, and barriers to care.<br><br>CONCLUSIONS: Stigma is pervasive among children with Long COVID, affecting many aspects of life including healthcare interactions and social relationships. Addressing both enacted and internalized stigma is essential to improving health and psychosocial outcomes in this population.<br><br>IMPACT: This article shows that stigma is pervasive and multifaceted in pediatric Long COVID, shaping children's health, social participation, and emotional well-being. It adds the first mixed-methods evidence combining quantitative and qualitative data to describe stigma experiences in this population. The study identifies specific stigma domains (alienation, discrimination, social withdrawal) linked to poorer health and functioning, highlighting areas for targeted intervention. The impact is to guide future clinical, educational, and policy efforts aimed at reducing stigma and improving outcomes for affected youth.},
}
@article {pmid42202985,
year = {2026},
author = {Sultana, S and Asai, Y and Ishioka, H and Ikeda, S and Ohtera, A and Matsunaga, N and Tsuzuki, S and Ohmagari, N},
title = {Self-Reported Long COVID Symptoms among Japanese Adults: Findings of CARE Japan Online Questionnaire-Based Prospective Cohort Study.},
journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy},
volume = {},
number = {},
pages = {103003},
doi = {10.1016/j.jiac.2026.103003},
pmid = {42202985},
issn = {1437-7780},
abstract = {INTRODUCTION: We conducted a comprehensive assessment of long COVID and associated risk factors, among an online cohort of Japanese adults in omicron dominant COVID-19 period in Japan.<br><br>METHODS: We used data from the online questionnaire-based CARE Japan Study, that collected data on patient demographics and information on post-COVID-19 symptoms. Long COVID, was defined as the presence of &#x2265;1 symptom for &#x2265;3 months after the initial COVID-19 infection. We performed Kaplan-Meier survival analysis to estimate the restricted mean resolution time (RMST) of long COVID and sex-stratified multivariable Cox proportional hazards model for hazard ratios (HRs) with 95% confidence interval (CIs).<br><br>RESULTS: The final analysis included 1071 patients with COVID-19. The cumulative prevalence of long COVID in the studied cohort was 66.7%. 32% of the respondents with long COVID reported fatigue and runny nose, and 20%-24% reported headache, cough, nasal congestion, and sore throat. The RMST of long COVID was 311.1 days for men and 323.9 days for women. Younger individuals were more likely to experience long COVID than older patients. Overweight, obese or underweight patients reported long COVID more frequently than patients with normal weight. Patients with pre-existing psychological disorders or seasonal allergies showed higher risks of long COVID than participants with no pre-existing psychological disorders or seasonal allergies.<br><br>CONCLUSIONS: The prolonged duration of symptoms may affect work ability and recovery, highlighting the need for continued follow-up and supportive care, including return-to-work support and access to outpatient services. These implications should be interpreted within the context of the cohort.},
}
@article {pmid42203277,
year = {2026},
author = {Antolini, L and Valsecchi, MG and Bussi, A and La Piana, G and Pagani, E and Pascarella, MG and Patroni, A and Pellegrino, I and Pozzi, A and Sorlini, M and Ticozzelli, M and Villa, M and Zappa, M and Russo, AG and Lucifora, C},
title = {Unveiling the burden of long covid in hospital and community settings: findings from the Post-Acute Sequelae of SARS-CoV-2 Network (PASCNET) cohort study in Italy's pandemic epicentre.},
journal = {BMJ open},
volume = {16},
number = {5},
pages = {e114399},
doi = {10.1136/bmjopen-2025-114399},
pmid = {42203277},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/epidemiology/therapy/complications ; Italy/epidemiology ; Middle Aged ; Male ; Adult ; Retrospective Studies ; Aged ; Post-Acute COVID-19 Syndrome ; *Hospitalization/statistics &amp; numerical data ; Female ; SARS-CoV-2 ; Incidence ; Pandemics ; Young Adult ; Adolescent ; Prospective Studies ; },
abstract = {OBJECTIVES: Post-COVID-19 condition (PCC) has emerged as a major public health concern. We aimed to estimate the 1-year incidence of PCC in adults with confirmed SARS-CoV-2 infection in Lombardy, Italy, comparing community-managed and hospitalised patients and to assess the prognostic value of the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) score to support estimation of long-term PCC prevalence.<br><br>DESIGN: Retrospective-prospective observational cohort study enrolling patients infected between 1 March 2020 and 31 December 2022. The study visit was conducted between 16 January and 23 December 2024.<br><br>SETTING: Multicentre study involving seven public hospitals and general practitioners across Lombardy.<br><br>PARTICIPANTS: Randomly sampled adults aged 18-70 years with confirmed SARS-CoV-2 infection. Hospitalised patients (HP) were admitted for COVID-19; general practitioner patients (GPP) were managed in the community. The total sample comprised: 1162 (546 HP, 616 GPP).<br><br>INTERVENTION: This is an observational study with no active intervention.<br><br>Primary outcome: 1-year incidence of PCC retrospectively assessed at the study visit.<br><br>SECONDARY OUTCOMES: symptom profiles, long-term PCC prevalence at the study visit and predictive value of the NIH RECOVER score.<br><br>RESULTS: Median age was 57.1 years in HP and 42.9 years in GPP; 66.1% of HP and 47.7% of GPP were male. PCC developed in 280 patients (223 HP, 57 GPP). The 1-year cumulative incidence was 39.9% in HP (95%&#x2009;CI 35.9% to 44.1%)&#x2009;and 9.1% in GPP (95%&#x2009;CI 7.1% to 11.7%). The NIH RECOVER score was associated with PCC at 1 year (OR 1.18, 95%&#x2009;CI 1.14 to 1.21). Model-based long-term PCC prevalence was 31.8% in HP and 6.3% in GPP.<br><br>CONCLUSIONS: PCC remained frequent and heterogeneous, particularly among previously HP. In this cohort, the NIH RECOVER score showed prognostic value for estimating longer-term PCC burden. These findings underscore the need for structured long-term follow-up across both hospital and primary care settings.},
}
@article {pmid42184698,
year = {2026},
author = {Gozalo-Margüello, M and González-Rico, C and Fariñas-Álvarez, C and Fernández-Sampedro, M and Arnaiz de Las Revillas, F and Parra-Fariñas, R and Runza-Buznego, P and Baldeón-Conde, C and Ferrer-Pargada, D and Portilla Chocarro, R and Abascal Carrera, I and Calvo-Montes, J and Ocampo-Sosa, A and Fariñas, MC and , },
title = {Persistent symptoms and healthcare utilisation during five-year follow-up after SARS-CoV-2 infection: A multicentre cohort study in Spain.},
journal = {Journal of infection and public health},
volume = {19},
number = {7},
pages = {103270},
doi = {10.1016/j.jiph.2026.103270},
pmid = {42184698},
issn = {1876-035X},
abstract = {OBJECTIVES: To describe long-term symptom persistence and healthcare utilisation related to SARS-CoV-2 infection over a five-year follow-up period in a multicentre cohort of patients with confirmed COVID-19 in Spain.<br><br>METHODS: We conducted a multicentre cohort study including individuals aged &#x2265;&#x202f;16 years with RT-PCR-confirmed SARS-CoV-2 infection in Cantabria, Spain, between March 2020 and March 2022. Early follow-up (1-2 years post-infection) involved in-person interviews using a standardised questionnaire. Late follow-up (5 years post-infection) was based on electronic health record review. Outcomes included persistent symptoms, long COVID diagnoses, and healthcare utilisation related to post-COVID symptoms.<br><br>RESULTS: The cohort included 266 participants (198 hospitalised and 68 non-hospitalised). Among 200 participants with available early follow-up, 112/200 (56.0%) reported at least one persistent symptom during the medium-term post-infection period (1-2 years after SARS-CoV-2 infection). Persistent symptoms occurred in 76/132 (57.6%) hospitalised participants and in 36/68 (53.0%) non-hospitalised participants. Fatigue was the most frequent symptom in both groups. Only 9 participants (3.4%) had a formal diagnosis of long COVID recorded in their medical records. Female sex, chest pain during acute infection, and smoking were associated with symptom persistence. At five-year follow-up, 38 participants (14.3% of the total cohort; 19.0% of those with early follow-up) sought healthcare for symptoms compatible with post-COVID conditions. However, these encounters were not formally attributed to prior SARS-CoV-2 infection in the medical records.<br><br>CONCLUSIONS: Persistent symptoms were common during the medium-term post-infection period, while formal long COVID diagnoses and healthcare encounters explicitly attributed to COVID-19 were relatively uncommon in routine clinical records at five years. These findings highlight the challenges of recognising and attributing long-term post-COVID manifestations in clinical practice and suggest that the burden of long-term post-COVID symptoms may be under-recognised in healthcare systems.},
}
@article {pmid42190841,
year = {2026},
author = {Fukunaga, N and Asakura, T and Terai, H and Tanaka, H and Azekawa, S and Iizuka, S and Ozawa, T and Nagao, G and Nakagawara, K and Morita, A and Atsumi, A and Yagi, K and Kaji, M and Ogata, A and Konishi, S and Matsuyama, E and Ito, F and Takaoka, H and Shigematsu, L and Shimada, T and Otake, S and Sunata, K and Okada, M and Fukushima, T and Ohgino, K and Masaki, K and Miyata, J and , },
title = {Association between corticosteroid therapy during acute COVID-19 and Long COVID symptoms: a propensity score overlap-weighted analysis.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108914},
doi = {10.1016/j.rmed.2026.108914},
pmid = {42190841},
issn = {1532-3064},
abstract = {BACKGROUND: The association between acute-phase corticosteroid therapy and subsequent Long COVID symptoms remains uncertain. Therefore, we aimed to evaluate the association between systemic corticosteroid therapy during hospitalization and patient-reported Long COVID symptoms during follow-up.<br><br>METHODS: In this prospective multicenter observational study, we enrolled adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 26 hospitals in Japan between January 2020 and February 2021. To account for evolving corticosteroid prescription practices, we used propensity score overlap weighting with calendar time adjustment relative to the RECOVERY trial announcement and fit overlap-weighted mixed-effects logistic regression models to estimate longitudinal associations across follow-up (3, 6, and 12 months). Additionally, symptom-specific outcomes were evaluated at 3 months.<br><br>RESULTS: Among the 1044 participants, 373 received systemic corticosteroids and 671 did not. Corticosteroid therapy was associated with higher odds of any Long COVID symptom during follow-up (OR: 1.71; 95% CI: 1.12-2.63). In exploratory subgroup analyses stratified by oxygen requirement, no clear association was observed among patients who required oxygen therapy during hospitalization, whereas the association was more apparent among those who did not require oxygen therapy. At 3 months, corticosteroid therapy was associated with muscle weakness (OR: 2.43; 95% CI: 1.27-4.65).<br><br>CONCLUSIONS: In this observational overlap-weighted analysis, acute-phase systemic corticosteroid therapy during COVID-19 hospitalization was associated with higher odds of patient-reported Long COVID symptoms during follow-up. However, these findings should not be interpreted as evidence against appropriately indicated corticosteroid therapy in patients with hypoxemic COVID-19 or respiratory failure.},
}
@article {pmid42194393,
year = {2026},
author = {Baloğlu, M},
title = {Neuropathic Symptoms and Persistent Pain After Hospitalization for COVID-19: An 8-Month Longitudinal Follow-Up Study.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
doi = {10.3390/healthcare14101300},
pmid = {42194393},
issn = {2227-9032},
abstract = {Background: Persistent pain, neuropathic symptoms, dyspnea, and impaired quality of life are common components of post-COVID syndrome. However, the long-term trajectory of these symptoms and the factors associated with persistent pain remain incompletely understood. Methods: This longitudinal cohort study included 80 patients previously hospitalized with COVID-19. Participants were evaluated at approximately 1, 4, and 8 months after discharge. Pain severity was assessed using the Visual Analog Scale (VAS), neuropathic symptoms using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, dyspnea using the modified Medical Research Council (mMRC) scale, functional limitation using the Post-CO9VID Functional Status (PCFS) scale, and health-related quality of life using the EQ-5D-5L and EQ-VAS scales. Functional performance was additionally assessed using the 30 s chair stand test and the Modified Borg Scale. Multivariable linear regression and logistic regression analyses were performed to identify predictors of reduced quality of life and persistent pain at 8 months. Results: A total of 80 patients were included in the study. Median VAS score decreased from 3.0 (0-6) at 1 month to 0 (0-0) at 4 months and 1 (0-1) at 8 months (p < 0.001). Median LANSS score decreased from 0 (0-2) at 1 month to 0 (0-0) at 4 and 8 months (p < 0.001), while the proportion of patients with LANSS ≥ 12 declined from 11.3% to 2.5%. EQ-5D index scores improved from 0.81 (0.72-0.91) to 0.93 (0.88-0.96) during follow-up (p < 0.001). Dyspnea severity, exertional symptoms, and functional limitation also improved significantly over time. Most of the clinical recovery occurred between the 1-month and 4-month evaluations, although smaller but significant improvements continued until 8 months for pain severity, functional performance, and quality-of-life measures. Older age, baseline dyspnea, anxiety, and higher baseline LANSS scores were independently associated with lower EQ-VAS scores at 8 months, whereas only higher baseline LANSS scores remained independently associated with persistent pain. Conclusions: Patients hospitalized with COVID-19 experience persistent pain, dyspnea, neuropathic symptoms, and reduced quality of life during follow-up, although most symptoms improve substantially over time. Early neuropathic symptom burden and baseline dyspnea may help identify patients at risk of poorer long-term recovery, although the associations should be interpreted cautiously.},
}
@article {pmid42194643,
year = {2026},
author = {Król-Kulikowska, M and Kepinska, M and Siwy, J and Keller, F and Mischak, H and Wendt, R and Sarenmalm, E and Nilsson, &#xc5; and Peters, B and Dudoignon, E and Zunara, F and Michel, M and Salgueira, M and Spasovski, G and Scholz, C and Wawrzonkowski, P and Banasik, M and UriCoV Working Group, },
title = {Post-Acute Sequelae of COVID-19 (PASC) in Hospitalized and Ambulatory Patients: A Comparative Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103681},
pmid = {42194643},
issn = {2077-0383},
support = {PerMed/V/80/UriCov/2023//National Centre for Research and Development/ ; 2523FSB114//Federal Ministry of Health/ ; 01KU2309//German Ministry for Education and Science/ ; 2022-00542//Sweden's innovation agency (Vinnova)/ ; ANR-22-PERM-0014//Agence Nationale de la Recherche/ ; I 6471//FWF Austrian Science Fund/ ; Grant-DOI 10.55776/I6471//ERA PerMed/ ; },
abstract = {Background/Objectives: COVID-19 may result in persistent symptoms, some of which can be disabling, referred to as post-acute sequelae of SARS-CoV-2 (PASC, or long COVID). The growing recognition of PASC as a public health challenge underscores the need for comprehensive studies of its course, risk factors, and clinical outcomes. This multicentric study aimed to compare the prevalence, symptom spectrum, and functional impact of PASC in two patient groups: those hospitalized with COVID-19 and those managed exclusively in ambulatory care. Methods: Molecular, clinical, and demographic data were obtained from 319 patients diagnosed with COVID-19 in seven European countries. Patients were classified as PASC in accordance with the WHO definition. Results: PASC is more frequent and severe among hospitalized patients, while ambulatory patients present with milder but prolonged symptoms. Categorical age analysis suggests that older age was associated with a higher incidence of PASC, highlighting the need for multidisciplinary management and targeted support. Conclusions: Our findings highlight distinct differences in the presentation and impact of PASC across patient groups, with important implications for individualized care, multidisciplinary management, and effective healthcare planning in the post-pandemic era.},
}
@article {pmid42194664,
year = {2026},
author = {Suyama, A and Otsuka, Y and Nakano, Y and Tokumasu, K and Sakurada, Y and Matsuda, Y and Honda, H and Soejima, Y and Hasegawa, T and Takase, R and Omura, D and Oguni, K and Ueda, K and Otsuka, F},
title = {Exploratory Analysis of Serum IGF-I Levels and Symptom Trajectories in Long COVID During the Omicron Period.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103702},
pmid = {42194664},
issn = {2077-0383},
support = {2025//Ofuji Endocrine Medical Award/ ; 2025//Kobayashi Magobe Memorial Medical Foundation/ ; 2025//Growth Science Foundation (2025)/ ; Grant Number JP26K20545//Kobayashi Magobe Memorial Medical Foundation/ ; },
abstract = {Background: Although several risk factors have been reported for long COVID (LC), reliable biomarkers for this illness remain lacking. Insulin-like growth factor (IGF)-I, a major mediator of growth hormones, plays an important role in metabolism, neuroprotection, and systemic homeostasis, and therefore may be useful in predicting the severity and prognosis of LC. Methods: This study included patients who visited a specialized clinic for long COVID between 2022 and 2025 during the Omicron period and had serum IGF-I measurements taken. IGF-I levels were expressed as age- and sex-adjusted standard deviation scores (IGF-I SD), and patients were classified into low (SD < -1.0), normal (-1.0 ≤ SD < 1.0), and high (SD ≥ 1.0) groups. Clinical characteristics, patient-reported outcomes, laboratory data, and follow-up duration were analyzed. Results: A total of 811 patients were included (median 42 years; 52.5% female). Compared with the normal group, the low-IGF-I group exhibited higher fatigue (FAS: 37.0 vs. 34.0; p < 0.05) and depressive (SDS: 50.0 vs. 49.0; p < 0.05) status. Multivariable linear regression analyses identified lower IGF-I SD as independently associated with higher scores of both FAS and SDS. IGF-I SD values showed negative correlations with ferritin (ρ = -0.125, p < 0.05) and TSH (ρ = -0.202, p < 0.01) and positive correlations with albumin (ρ = 0.227, p < 0.01) and FT4 (ρ = 0.165, p < 0.01). Among the 237 patients who completed follow-up, the median duration from the initial visit to recovery tended to be longer in the low-IGF-I group (221 days) compared with the normal (191 days) and high (109 days) groups, although these differences were not statistically significant overall. In patients aged < 50 years, the low-IGF-I group showed a relatively longer follow-up duration (p < 0.05). Furthermore, the low-IGF-I group had a longer time to recovery compared to the high-IGF-I group (p < 0.05), and this difference was more pronounced in patients under 50 years of age, with significant differences observed among the three IGF-I groups. Conclusions: Lower IGF-I levels in LC may be associated with greater fatigue and depressive symptoms and longer recovery time, particularly in younger patients. Further studies are needed to clarify the clinical significance of these findings.},
}
@article {pmid42194670,
year = {2026},
author = {Sołomacha, S and Alimowski, M and Moniuszko-Malinowska, A and Kiszkiel, &#x141; and Laskowski, P and Dubatówka, M and Sowa, P and Kamiński, K},
title = {Symptom Trajectories and Long-Term Sequelae of COVID-19: A Matched Case-Control Study with Population-Based Controls.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103707},
pmid = {42194670},
issn = {2077-0383},
support = {2020/37/B/NZ7/03380//National Science Centre/ ; },
abstract = {Background/Objectives: Post-COVID-19 condition involves heterogeneous, multisystem symptoms with uncertain recovery. We characterized symptom trajectories from hospitalization to approximately 4 weeks and to 6-8 months and compared the 6-8-month symptom burden with season-matched controls, accounting for serology-identified, previously unrecognized infections. Methods: An individually pair-matched case-control study of adults with RT-PCR-confirmed SARS-CoV-2 and population controls from the Bialystok PLUS cohort, matched on age, sex and a two-month visit window, was performed. All participants underwent anti-nucleocapsid serology. Hospitalized cases were reassessed at approximately 4 weeks and 6-8 months. Cross-sectional outcomes used non-parametric tests and multivariable regression; longitudinal change used paired tests and generalized estimating equations. Results: We included 402 adults (201 post-COVID-19; 201 controls). In hospitalized cases, respiratory symptoms declined rapidly by approximately 4 weeks and remained low at 6-8 months; smell/taste recovered more slowly; fatigue improved modestly; anxiety changed minimally. At 6-8 months, total symptom counts were higher in post-COVID-19 than in controls (median 4 vs. 2), with serology-positive controls intermediate (median 3). Excess burden was concentrated in non-respiratory domains (fatigue, neurocognitive, cardiovascular, and dermatologic), whereas respiratory differences were not significant. In the multivariable model, female sex remained an independent predictor of higher multisystem burden, whereas age, body mass index, hospitalization, and acute biomarker severity were not associated. Conclusions: Six to eight months after symptomatic COVID-19, multisystem symptom burden remains substantial relative to season-matched controls, despite substantial resolution of respiratory complaints. Serology-based identification of previously unrecognized infections indicates an intermediate burden and can guide targeted follow-up.},
}
@article {pmid42194942,
year = {2026},
author = {Brindisi, G and Gori, A and Pignataro, E and Colletti, G and Iavarone, S and Spalice, A and Anania, C and Zicari, AM},
title = {Allergic Status, Long COVID, and Post-Restriction Respiratory Outcomes in Children: A Single-Center Questionnaire-Based Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103982},
pmid = {42194942},
issn = {2077-0383},
abstract = {Background: The relationship between allergic status, SARS-CoV-2 infection, Long COVID, and post-restriction respiratory outcomes in children remains incompletely understood. This study aimed to explore the associations between allergic status and Long COVID, as well as between SARS-CoV-2 vaccination and post-restriction changes in allergic rhinitis (AR), asthma, and upper respiratory infections, in a pediatric tertiary-care cohort. Methods: We conducted a single-center, questionnaire-based observational study involving children aged 0-16 years, who were followed at the Pediatric Allergy Clinic of Umberto I Hospital in Rome. Parents completed an email-based questionnaire addressing SARS-CoV-2 infection, vaccination, persistent post-infectious symptoms, allergic diseases, and respiratory infections following restrictions. Analyses of Long COVID were limited to children with confirmed SARS-CoV-2 infection. Results: A total of 214 questionnaires were analyzed. Allergic status was not significantly associated with SARS-CoV-2 infection in the overall cohort. Among infected children, allergic status was independently associated with higher odds of Long COVID (adjusted OR 3.12, 95% CI 1.20-8.09; p = 0.019). Severe acute infection was also strongly associated with Long COVID (adjusted OR 6.84, 95% CI 2.72-17.21; p < 0.001). Complete vaccination was associated with lower odds of SARS-CoV-2 infection in the overall sample (adjusted OR 0.20, 95% CI 0.09-0.46; p < 0.001) but was not independently associated with Long COVID among infected children. After the removal of COVID-19 restrictions, 90.1% of allergic children reported worsening AR and 52.0% reported worsening asthma, with no significant association with SARS-CoV-2 infection or Long COVID. Group A Streptocossus (GAS) pharyngitis was reported in 50.0% and viral pharyngitis in 10.7% of the cohort, with no significant differences between allergic and non-allergic children. Conclusions: In this single-center, questionnaire-based pediatric cohort, allergic status was correlated with increased likelihood of Long COVID among children with confirmed SARS-CoV-2 infection; however, it was not associated with a higher risk of infection itself. Complete vaccination was linked to a reduced risk of infection, whereas no independent correlation with Long COVID was identified. Post-restriction exacerbation of allergic respiratory symptoms was prevalent, while the incidence of bacterial and viral pharyngitis did not vary significantly according to allergic status.},
}
@article {pmid42196466,
year = {2026},
author = {Petrov, S and Bozhkova, M and Ivanovska, M and Kalfova, T and Dudova, D and Todorova, Y and Dimitrova, R and Murdjeva, M and Taskov, H and Nikolova, M and Maes, M},
title = {Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID.},
journal = {International journal of molecular sciences},
volume = {27},
number = {10},
pages = {},
doi = {10.3390/ijms27104488},
pmid = {42196466},
issn = {1422-0067},
support = {Contract No BG-RRP-2.004-0007-C01//Strategic Research and Innovation Programme for the Development of the Medical University-Plovdiv (SRIPD-MUP)/ ; },
mesh = {Humans ; *Dendritic Cells/immunology/metabolism ; *Monocytes/immunology/metabolism ; *COVID-19/immunology/physiopathology/pathology ; Immunophenotyping/methods ; Female ; *Fatigue Syndrome, Chronic/immunology/physiopathology/pathology ; Male ; Post-Acute COVID-19 Syndrome ; Receptors, CCR7/metabolism ; Middle Aged ; Adult ; SARS-CoV-2/immunology ; Flow Cytometry ; B7-1 Antigen/metabolism ; T-Cell Exhaustion ; T-Lymphocyte Subsets/immunology ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long Coronavirus Disease 2019 (long COVID) are complex chronic conditions that often follow infectious triggers with overlapping clinical features but poorly defined pathophysiological relationships. This study aimed to identify disease-specific immune signatures through multiparameter immunophenotyping of monocytes, dendritic cells, and T cell subsets. A total of 207 participants were included (ME/CFS: n = 103; long COVID: n = 63; healthy controls: n = 41). Peripheral blood mononuclear cells were analyzed using multiparameter flow cytometry. Statistical analyses included non-parametric testing, age-adjusted Analysis of covariance (ANCOVA), correlation network analysis, and principal component analysis (PCA). Long COVID was characterized by increased M2-like monocyte polarization, elevated CD80 expression across monocyte subsets, expansion of dendritic cells, and reduced expression of activation markers, indicating persistent immune activation with features of immune exhaustion. In contrast, ME/CFS exhibited reduced costimulatory molecule expression, impaired C-C chemokine receptor type 7 (CCR7)-mediated immune cell trafficking, and less coordinated activation patterns, consistent with a state of immune suppression. Correlation network analysis revealed more extensive and integrated immune interactions in long COVID, while PCA identified distinct immunophenotypic components and enabled moderate discrimination between the two conditions. These findings demonstrate that ME/CFS and long COVID are characterized by distinct immune profiles, supporting the concept of divergent immunopathological mechanisms. The identified signatures may contribute to biomarker development and guide targeted therapeutic approaches.},
}
@article {pmid42196834,
year = {2026},
author = {Guindani, N and Gaffuri, M and Bonaffini, PA and Valle, C and Caruso, A and Carioli, G and Fenili, F and Zangari, R and Sironi, S and Chiodini, F and Castelli, CC},
title = {Prevalence of Osteonecrosis of the Femoral Head in High-Risk Male Patients with Severe COVID-19 Treated with High-Dose Corticosteroids: A Prospective Cohort Study Using Screening MRI-How Many Have Been Left Behind?.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {10},
pages = {},
doi = {10.3390/diagnostics16101466},
pmid = {42196834},
issn = {2075-4418},
abstract = {Objectives: The association between osteonecrosis (ON) and Coronavirus Disease of 2019 (COVID-19) was reported early during the pandemic. ON of the femoral head (ONFH) is particularly problematic, as it may destroy the joint and lead to arthroplasty, although early diagnosis and treatment might mitigate its progression. The aim of the present study was to quantify the prevalence of symptomatic and asymptomatic ONFH in patients with severe COVID-19 treated with high doses of corticosteroids during the first pandemic wave. Methods: For this prospective, observational, monocentric cohort study, patients were selected according to the risk factors described for severe acute respiratory syndrome coronavirus in 2002-2004 (SARS-1): young males (<61 years old), high cumulative cortisone doses (≥2 g), severe disease, and followed up clinically and with magnetic resonance imaging. ONFH was classified with the ARCO classification. Results: Out of 1944 patients admitted for COVID-19 from 23 February to 21 May 2020, 856 of 1944 were treated in ICU; 30/1944 were selected according to the inclusion criteria and 27 of 30 were enrolled. The mean age at admission was 54 years (range, 42-60). The mean dose of cumulative cortisone was 6.25 g (range, 2-16). A total of 4/27 (15%) patients had ONFH; only 2 of 4 (50%) were symptomatic, including 1 with multiple ON of major joints. Conclusions: A high-risk cohort of patients with COVID-19 and high doses of corticosteroids had a 15% rate of ONFH, and 2 years after the event, 50% of them were asymptomatic. For those patients, relying solely on clinical evaluation would risk underestimating ONFH, potentially influencing treatment and outcomes. Moreover, other joints might develop ON. The data collected in the present study can be considered for the management of long-COVID. The association between severe COVID-19, high doses of corticosteroids and ONFH suggests the need for focused clinical and magnetic resonance imaging, considering the high rate of asymptomatic patients.},
}
@article {pmid42197510,
year = {2026},
author = {Manta, BA and Mateescu, DM and Iurciuc, S and Precup, CV and Pescaru, CC and Tischer, AA},
title = {Clinical Outcomes, Inflammatory Profile, Bacterial Co-Infections and Post-Acute Symptom Burden in Hospitalised COVID-19 Patients During the Omicron BA.5 Wave: A Single-Centre Cohort Study from Western Romania.},
journal = {Microorganisms},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/microorganisms14051124},
pmid = {42197510},
issn = {2076-2607},
support = {Victor Babe&#x219; University of Medicine and Pharmacy Timi&#x219;oara//Victor Babe&#x219; University of Medicine and Pharmacy Timi&#x219;oara/ ; },
abstract = {Evidence on hospitalised COVID-19 patients during the Omicron BA.5 wave from Eastern European, vaccine-heterogeneous cohorts remains limited. We conducted a retrospective single-centre cohort study of 395 consecutive adults admitted with laboratory-confirmed COVID-19 to a tertiary infectious-diseases unit in western Romania between 1 July and 31 October 2022. Median age was 72 years (IQR 65-81); 33.2% were unvaccinated, 42.8% had documented prior SARS-CoV-2 infection, and 41.3% were obese. Multivariable logistic regression identified independent predictors of in-hospital mortality and post-acute symptom burden. In-hospital mortality was 15.7% (62/395). Vaccination was independently associated with lower mortality (adjusted odds ratio [aOR] 0.55, 95% CI 0.30-0.99; p = 0.048), as was each 1% increase in admission SpO2 (aOR 0.83, 95% CI 0.76-0.92; p < 0.001), whereas COPD independently increased mortality risk (aOR 2.42, 95% CI 1.15-5.10; p = 0.020). Interleukin-6 was the most discriminating admission biomarker for in-hospital mortality (AUROC 0.70). Bloodstream bacterial co-infection, detected in 22.5% of patients tested on clinical suspicion, was dominated by gut-derived organisms with case-fatality ≥30%. At discharge, 90.1% reported persistent symptoms, most commonly cognitive (24.6%). Prior SARS-CoV-2 infection independently predicted post-acute symptom burden (aOR 2.96, 95% CI 1.75-5.01; p < 0.001), with a specific cardiopulmonary signature. In this BA.5 cohort, vaccination remained protective; IL-6 was the most informative admission biomarker; bloodstream infections suggested gut translocation; and prior infection was an independent determinant of early post-acute symptom burden.},
}
@article {pmid42199154,
year = {2026},
author = {Li, Y and Chen, L and Zhang, Y and Lin, CY and Jiang, X and Sun, S and Jiang, H and Ge, X and Zhang, Z and Fu, H and Zhang, Y and Wu, D},
title = {Site-Specific Olfactory Cleft Opacification Predicts Olfactory Function and Olfactory Training Outcome in Persistent Postinfection Olfactory Dysfunction.},
journal = {International forum of allergy &amp; rhinology},
volume = {},
number = {},
pages = {},
doi = {10.1002/alr.70190},
pmid = {42199154},
issn = {2042-6984},
support = {BYSYZD2023029//the Key clinical projects of Peking University Third Hospital/ ; BYSYDL2025021//Peking University Third Hospital Clinical Cohort Construction Project/ ; 82000954//Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Persistent postinfectious olfactory dysfunction (PIOD) is a prevalent and often refractory condition, with low recovery rates following olfactory training (OT), primarily due to sustained localized inflammation and opacification within the olfactory cleft (OC). However, conventional radiological assessments of OC opacification overlook the vertical distribution of olfactory neuroepithelium, limiting prognostic accuracy. This study introduces a modified subregion computed tomography (CT) scoring system integrated with computational fluid dynamics (CFD) to evaluate OC opacification's role in baseline olfaction and OT efficacy.<br><br>METHODS: In this prospective study, 58 adults with persistent PIOD of more than 3 months' duration were enrolled and completed CT imaging, psychophysical olfactory testing (Sniffin' Sticks TDI score), and questionnaire assessments. Using a modified scoring system, the OC was segmented on coronal sections into upper (superior one-third) and lower (inferior two-thirds) portions, with three coronal sections assessed in both the anterior and posterior OC. Each section was scored dichotomously (0 for no opacification, 1 for opacification), and bilateral scores were recorded. Unsupervised K-means clustering identified phenotypes, random forest modeling predicted functional anosmia, and CFD analyzed airflow dynamics. Thirty-one patients completed 3-month OT with follow-up assessments.<br><br>RESULTS: OC opacification was present in 69.0% of persistent PIOD patients, with opacification in the upper posterior OC notably serving as the primary determinant of baseline olfactory function. Random forest analysis further confirmed that upper OC opacification ranked as the top predictor for functional anosmia, with the combined model achieving an area under the curve of 0.920. Cluster analysis revealed three distinct phenotypes, among which the diffuse severe opacification cluster involving upper OC regions was associated with the poorest olfactory function. Although posterior OC opacification was positively correlated with increased airflow velocity ratios (r&#xa0;=&#xa0;0.570, p&#xa0;<&#xa0;0.01) and these ratios were negatively correlated with olfactory scores, OC airflow itself did not significantly mediate the relationship between structure and olfactory function. Only 25.8% of patients achieved clinically meaningful olfactory improvement. Significant improvements were observed in TDI (p&#xa0;=&#xa0;0.001), olfactory threshold (p&#xa0;=&#xa0;0.010), olfactory discrimination (p&#xa0;=&#xa0;0.028), and olfactory VAS scores (p&#xa0;<&#xa0;0.001) after OT. Baseline opacification in posterior-middle section of OC significantly predicted non-response.<br><br>CONCLUSIONS: The modified subregion OC opacification scoring system provides a more refined assessment of site&#x2011;specific OC obstruction for patients with persistent PIOD, underscoring the critical role of OC opacification in mediating olfactory impairment and resistance to OT.<br><br>CLINICAL IMPLICATION: For patients with persistent PIOD, this modified olfactory cleft opacification scoring system allows for olfactory assessment and prognosis by identifying specific opacification patterns associated with olfactory training outcomes.},
}
@article {pmid42200125,
year = {2026},
author = {Martín-Sanz, MB and Moro-López-Menchero, P and Fernández-De-Las-Peñas, C and Gómez-Sánchez, SM and Gil-Crujera, A and Ceballos-García, L and Escribano-Mediavilla, NI and Fuentes-Fuentes, MV and Florencio, LL and Palacios-Ceña, D},
title = {Challenges to continuity of care among patients with long COVID-related taste and smell disorders: a qualitative study.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1784507},
pmid = {42200125},
issn = {2296-2565},
mesh = {Humans ; Female ; *COVID-19/complications/therapy ; Male ; Middle Aged ; Qualitative Research ; *Continuity of Patient Care ; *Taste Disorders/etiology/therapy ; *Olfaction Disorders/therapy/etiology ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; Spain ; SARS-CoV-2 ; Interviews as Topic ; },
abstract = {Taste and smell disorders are predominant symptoms of acute SARS-CoV-2 infection and can persist in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID. These sensory impairments continue to significantly affect daily life and wellbeing, yet clinical understanding and care strategies remain insufficient. There is an ongoing need to address the specific healthcare requirements of this population. The aim of this study was to describe the experiences and perceptions of individuals with Long COVID related taste and smell disorders regarding symptom management and the challenges affecting continuity of care. A qualitative descriptive study was conducted in 2024 in the Community of Madrid (Spain) using purposive sampling. Data were collected through in-depth interviews and analyzed using thematic analysis, an approach appropriate for examining patient experiences in healthcare. Twelve participants with previously confirmed SARS-CoV-2 infection and persistent loss and/or impairment of taste and smell were interviewed. Four themes were identified: (a) Implications of Long COVID taste and smell disorders, (b) Expectations regarding prognosis and symptom cure, (c) Professional approach and symptom management, (d) Barriers and facilitators to continuity of care. Findings highlight the clinical and social relevance of taste and smell disorders in Long COVID and illustrate how qualitative methods can capture patient perspectives that may inform future mixed-methods research.},
}
@article {pmid42200220,
year = {2026},
author = {O'Donnell, A and Simon, ID and Iademarco, MF},
title = {More Attention on Infection-Associate Chronic Conditions Requires Restoring Support for Long COVID.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag332},
pmid = {42200220},
issn = {1537-6591},
}
@article {pmid42201014,
year = {2026},
author = {Pinto, EF and Albuquerque Filho, NJB and Leite, JC and Gusmão, TME and de Souza, LN and Silva Júnior, RRD and Knackfuss, MI and Piuvezam, G},
title = {Exercise-Based Rehabilitation in Severe COVID-19 Survivors with Long COVID: A Randomized Controlled Pilot Study.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
doi = {10.3390/medsci14020222},
pmid = {42201014},
issn = {2076-3271},
mesh = {Humans ; *COVID-19/rehabilitation/physiopathology ; Female ; Pilot Projects ; Quality of Life ; Male ; Middle Aged ; SARS-CoV-2 ; *Exercise Therapy/methods ; Survivors ; Aged ; Post-Acute COVID-19 Syndrome ; Pandemics ; Muscle Strength ; },
abstract = {INTRODUCTION: Post-hospital rehabilitation is essential for survivors of severe COVID-19, as prolonged immobility and clinical severity often lead to muscle weakness, reduced cardiovascular capacity, and impaired respiratory function. Physical exercise during and after hospitalization may mitigate these effects and support functional recovery. This study aimed to evaluate the effectiveness of a physical exercise-based rehabilitation program in survivors of severe COVID-19.<br><br>METHODOLOGY: A randomized clinical trial was conducted with 30 survivors allocated to two groups: multicomponent exercise (GEm) and multicomponent exercise combined with inspiratory muscle training (GEmTMI). The interventions were performed three times per week for 40-60 min. Quality of life, physical activity level, functional status, and physical capacity were assessed before and after six weeks.<br><br>RESULTS: Comparisons between GEm and GEmTMI showed significant differences in the 6 min walk test (6MWT) at baseline (p = 0.043) and in the Physical Activity Index (IPAQ) after the intervention (p = 0.002). When the total sample was analyzed, significant improvements were observed across all outcomes after rehabilitation, including quality of life (SF-36), functional capacity (PCFS), physical activity level (IPAQ), respiratory muscle strength, and additional functional tests. Notable improvements included SF-36 Physical Functioning (p = 0.006) and Social Functioning (p = 0.009), PCFS (p = 0.011), IPAQ (p = 0.012), and performance in the 6MWT, STS, STS-1min, TUG, handgrip strength, PEmax, and PImax (all p < 0.001).<br><br>DISCUSSION: Multicomponent physical rehabilitation, with or without inspiratory muscle training, produced significant gains in physical activity level, functional capacity, dynamic balance, neuromuscular fitness, respiratory muscle strength, and quality of life. These findings underscore the importance of structured post-ICU rehabilitation to support comprehensive physical and psychosocial recovery in survivors of severe COVID-19.},
}
@article {pmid42201061,
year = {2026},
author = {Smit, A and Fleischmann, P and Knauer, TS and Mardin, CY and Michelson, G and Zott, J and Güttes, M and Sarmiento, H and Ilgner, M and Jakobi, M and Rech, J and Hohberger, B},
title = {Task-Evoked Pupillary Dynamics Are Altered in Post-COVID Syndrome.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
doi = {10.3390/medsci14020269},
pmid = {42201061},
issn = {2076-3271},
support = {2490-PC-2021-V14//Bavarian Health and Food Safety Authority/ ; Gesamt-2490- 252 PCS-2023-V6//Bavarian Health and Food Safety Authority/ ; GRK 2504/1//Deutsche Forschungsgemeinschaf/ ; 01EO2105//Federal Ministry 254 of Education and Research/ ; },
mesh = {Humans ; Female ; Male ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Cross-Sectional Studies ; *COVID-19/physiopathology/complications ; *Pupil/physiology ; Adult ; Aged ; SARS-CoV-2 ; },
abstract = {Background/Objectives: Post-COVID syndrome (PCS) is frequently associated with persistent cognitive complaints such as fatigue and impaired concentration, yet objective markers related to cognitive dysfunction are lacking. Pupillary oscillation metrics have emerged as non-invasive indicators of task-related cognitive load and autonomic regulation. This study investigated the Index of Pupillary Activity (IPA) and the Low/High Index of Pupillary Activity (LHIPA) in a large cohort of patients with PCS compared with healthy controls. Methods: In this cross-sectional study, 526 participants (397 PCS patients, 129 controls) performed a standardized virtual reality-based stereoscopic task at three disparity levels: 275 arcsec (high difficulty), 550 arcsec (medium difficulty), and 1100 arcsec (low difficulty), using a head-mounted display with integrated eye tracking. Continuous pupillometry data were recorded, and IPA and LHIPA were calculated. Linear mixed-effects models with random intercepts for participants were applied, adjusting for age, sex, and task difficulty. Results: Both IPA and LHIPA were significantly lower in PCS patients than in controls at all three task difficulty levels in post hoc model-based contrasts. In adjusted mixed-effects models, PCS was also associated with lower overall IPA (β=-0.111, 95% CI -0.160 to -0.062, p<0.001) and lower overall LHIPA (β=-0.164, 95% CI -0.253 to -0.074, p<0.001). Lower task difficulty was associated with higher values of both metrics: for IPA, β=0.164 at 550 arcsec and β=0.287 at 1100 arcsec (both p<0.001); for LHIPA, β=0.161 at 550 arcsec and β=0.254 at 1100 arcsec (both p<0.001), relative to 275 arcsec. Thus, both indices showed an inverse association with task difficulty. Age was negatively associated with both metrics, whereas male sex was positively associated with both. No significant interaction between cohort and task difficulty was observed. Conclusions: PCS was associated with reduced IPA and LHIPA during a standardized stereoscopic task. These findings indicate altered task-related pupillary dynamics in PCS and may reflect altered cognitive-load processing and autonomic regulation. LHIPA, and with caution also IPA, may contribute to the objective assessment of task-related pupillary alterations in PCS.},
}
@article {pmid42201733,
year = {2026},
author = {Tian, J and Azhir, A and Decaro, M and Chau, N and Hügel, J and Morris, M and Cheng, J and Fard, P and Bassett, IV and Bell, DS and Bernstam, EV and Visweswaran, S and Klann, JG and Murphy, SN and Estiri, H},
title = {Long COVID Persistence and Surveillance Gaps Across 58 US Hospitals.},
journal = {JAMA network open},
volume = {9},
number = {5},
pages = {e2614909},
doi = {10.1001/jamanetworkopen.2026.14909},
pmid = {42201733},
issn = {2574-3805},
mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Female ; Retrospective Studies ; United States/epidemiology ; Male ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Adult ; Hospitals/statistics &amp; numerical data ; SARS-CoV-2 ; Aged ; Prevalence ; Chronic Disease/epidemiology ; Population Surveillance ; },
abstract = {IMPORTANCE: Surveillance of postacute sequelae of SARS-CoV-2 infection (PASC) depends on diagnostic coding systems that capture fewer than one-half of affected individuals, rendering millions invisible to health systems and policymakers.<br><br>OBJECTIVE: To quantify the gap between true PASC burden and diagnostic code-based estimates, determine the proportion representing chronic disease, and characterize organ system heterogeneity and temporal trends across diverse populations.<br><br>This retrospective cohort study used electronic health record data from 58 hospitals and affiliated clinics in 4 US regions, from 2017 to 2025. Adults (aged &#x2265;18 years) with laboratory-confirmed SARS-CoV-2 infection or a COVID-19 diagnosis code were included. A custom artificial intelligence algorithm, the Precision Phenotyping for Research Cohorts (P2RC), was implemented using federated infrastructure.<br><br>EXPOSURE: Laboratory-confirmed SARS-CoV-2 infection or COVID-19 diagnosis code.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcomes were PASC prevalence, the proportion classified as chronic conditions, organ system distribution, and temporal trends from 2020 to 2024. &#x3c7;2 Tests were used to assess organ system heterogeneity across regions, and negative binomial regression was used to model quarterly temporal trends, yielding incidence rate ratios (IRRs) with 95% CIs.<br><br>RESULTS: In this cohort study of 457&#x202f;950 COVID-19 cases (mean age, 52.05 years; 275&#x202f;107 [60.07%] female), the P2RC algorithm identified 74&#x202f;560 PASC cases (16.28% overall; 28&#x202f;585 [18.58%] in New England, 978 [19.55%] in Southeast Texas, 10&#x202f;534 [22.69%] in Southern California, and 34&#x202f;463 [13.64%] in Western Pennsylvania), more than 2-fold higher than the proportion identified by code-based surveillance (<7%). Of 883 International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes associated with PASC, 594 (67.27%) represented chronic or potentially chronic conditions. Of 74&#x202f;560 patients with PASC, 66&#x202f;587 (89.31%) developed chronic conditions requiring ongoing clinical management; this represents 14.54% of the total number of 457&#x202f;950 patients with COVID-19. Substantial organ system heterogeneity was observed (&#x3c7;2&#x2009;=&#x2009;2504.73; P&#x2009;<&#x2009;.001): New England demonstrated thyroid-predominant endocrine patterns, while Southeast Texas, Southern California, and Western Pennsylvania showed metabolic-predominant profiles. Negative binomial regression revealed increasing PASC prevalence through mid-2024 (IRR per quarter, 1.01 [95% CI, 1.00-1.01; P&#x2009;<&#x2009;.001] in New England; 1.00 [95% CI, 1.00-1.01; P&#x2009;<&#x2009;.001] in Southern California; and 1.02 [95% CI, 1.01-1.02; P&#x2009;<&#x2009;.001] in Western Pennsylvania), indicating an accumulating rather than resolving burden.<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, approximately 1 in 6 patients with COVID-19 developed PASC, and 89.31% of these patients had at least 1 chronic condition. Current diagnostic coding captured fewer than one-half of the cases, obscuring a substantial chronic disease burden. The persistently increasing prevalence through 2024 indicated an accumulating health care burden requiring investment in surveillance infrastructure and integrated care pathways.},
}
@article {pmid42201907,
year = {2026},
author = {Sirotiak, Z and Oberhauser, AM and Sirotiak, AM and Nettleton, KA and Lee, DC and Thomas, EBK and Brellenthin, AG},
title = {Exploring the perceived impact of physical activity on physical and mental health among individuals with long COVID: A qualitative interview inquiry.},
journal = {PloS one},
volume = {21},
number = {5},
pages = {e0350121},
doi = {10.1371/journal.pone.0350121},
pmid = {42201907},
issn = {1932-6203},
mesh = {Humans ; Female ; Middle Aged ; *COVID-19/psychology ; *Mental Health ; Male ; *Exercise/psychology ; Post-Acute COVID-19 Syndrome ; Adult ; Aged ; SARS-CoV-2/isolation &amp; purification ; Qualitative Research ; Symptom Burden ; Health Status ; },
abstract = {OBJECTIVES: Long COVID presents a significant health burden with limited treatment options. Physical activity (PA) has been suggested for self-management, yet symptom worsening has been reported in similar patient populations. This study aims to identify PA's perceived impact on physical and mental health in adults with long COVID.<br><br>METHODS: Semi-structured interviews were conducted with 34 adults (mean age 52 years, 62% women) based in the United States (U.S.) self-reporting long COVID. PA-related content was analyzed using deductive thematic analysis, assessing worsened and improved health experiences attributed to PA.<br><br>RESULTS: Participants' perceived health scores were one standard deviation worse than the general U.S. population. Most participants (64.7%) reported worsening long COVID symptoms with PA, while 14.7% noted improvement. Themes for worsened physical health included post-exertional malaise, specific symptom worsening (e.g., fatigue), limited PA abilities, external control perceptions, forced inactivity, and loss of previous PA abilities. Improved health themes involved beliefs in health benefits, symptom improvement, increased energy, accomplishment, enhanced PA abilities, and hope.<br><br>DISCUSSION: PA's impact on health varied among individuals with long COVID, highlighting the need to tailor PA recommendations to individual needs and limits.},
}
@article {pmid42183165,
year = {2026},
author = {Uddin, AS and Bulusu, S and Oderinde, OM and Zheng, QH},
title = {Positron emission tomography imaging of T-cell activity in cardiovascular disease and its emerging role in imaging adaptive immunity.},
journal = {American journal of nuclear medicine and molecular imaging},
volume = {16},
number = {2},
pages = {77-89},
pmid = {42183165},
issn = {2160-8407},
abstract = {T lymphocytes are central mediators of cardiovascular disease, driving myocardial injury in myocarditis, transplant rejection, post-infarct remodeling, atherosclerosis, and post-viral syndromes. Yet current imaging tools ([[18]F]FDG PET, somatostatin receptor tracers, CXCR4 PET, and cardiac MRI) offer only indirect or nonspecific measures of immune activity. The ability to noninvasively visualize and quantify T-cell infiltration and activation could transform diagnosis and management in cardio-immunology. Advances in immuno-PET have produced a growing arsenal of T-cell specific tracers. CD8-targeted agents ([89]Zr-Df-IAB22M2C) and small-molecule probes such as [[18]F]F-AraG have entered early clinical trials, demonstrating feasibility and safety in humans. Other tracers, including CD4- and CD3-directed antibodies, IL-2R and OX40 probes, checkpoint tracers (PD-1, CTLA-4), and granzyme B ligands, remain largely preclinical but show strong potential for cardiovascular translation. Applications span acute myocarditis, noninvasive transplant rejection surveillance, assessment of post-MI immune remodeling, plaque vulnerability in atherosclerosis, and systemic immune activation in long COVID. Compared with existing imaging modalities, T-cell PET offers cell-type specificity, quantitative longitudinal monitoring, and the capacity for whole-body immune mapping, particularly when integrated with total-body PET or hybrid PET/MR. Challenges include low T-cell density in the myocardium, tracer specificity, radiation burden, and the need for histopathologic validation. Future directions involve repurposing oncology tracers for cardiology, engineering antibody fragments with improved kinetics, and establishing T-cell PET as a mechanistic biomarker in cardiovascular clinical trials. With further innovation and validation, T-cell PET has the potential to evolve from an experimental tool into a clinically actionable modality, reshaping the management of immune-mediated heart disease.},
}
@article {pmid42175344,
year = {2026},
author = {Kaufmann, B and Hess, G and Cvijic, L and Denecke, K},
title = {Long Covid and Digital Health in Switzerland: Potentials and Limitations.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {2284-2288},
doi = {10.3233/SHTI260677},
pmid = {42175344},
issn = {1879-8365},
mesh = {Switzerland/epidemiology ; *COVID-19/therapy/epidemiology ; Humans ; *Telemedicine/statistics &amp; numerical data/organization &amp; administration ; *Mobile Applications ; SARS-CoV-2 ; Digital Health ; },
abstract = {Post-COVID-19 (or Long Covid) presents a complex and persistent health challenge affecting a growing number of individuals worldwide. Digital health interventions (DHIs) offer potential support for symptom monitoring, self-management, and information access. However, their availability, quality, and sustainability remain uncertain, particularly in smaller healthcare markets such as Switzerland. This study provides a descriptive assessment of ten representative DHIs for Long Covid available from Switzerland. Each tool was evaluated using a 19-item framework derived from validated instruments. Three independent reviewers tested all interventions on iOS and Android devices, with consensus ratings across five quality categories. Results showed strong usability (average 6.3/8) and practical usefulness (5/8), but consistent weaknesses in accessibility (3.7/8) and data protection (4.6/8). Total scores ranged from 14.7 to 26.3 out of 38. Several Swiss-based apps were discontinued during the study period, highlighting market fragility. Findings underscore the need for inclusive design, transparent data practices, and institutional support if DHIs are to complement Long Covid care sustainably.},
}
@article {pmid42178526,
year = {2026},
author = {Tsai, YT and Wang, BY and Ho, SW and Yang, SF and Wang, YH and Yeh, CB and Chen, YC},
title = {Association of long-COVID with major adverse cardiovascular events and mortality: a real-world data cohort study.},
journal = {BMC cardiovascular disorders},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12872-026-06026-x},
pmid = {42178526},
issn = {1471-2261},
support = {CSH-2023-A-007//Chung Shan Medical University Hospital/ ; },
abstract = {BACKGROUND: There is a limited body of research examining the association between long COVID and major adverse cardiovascular events (MACE) as well as all-cause mortality. This study aimed to investigate the association between long COVID and both MACE and mortality.<br><br>METHODS: This retrospective cohort study utilized multicenter real-world data from the TriNetX research network platform, which contains electronic health records from multiple healthcare organizations. Patients aged 18 years and older who were diagnosed with COVID-19 between 2020 and 2023 were included. The exposure group comprised individuals diagnosed with long-COVID within 3 to 6 months after their initial COVID-19 diagnosis, while the comparison group included COVID-19 patients without a diagnosis of long-COVID. The primary outcomes were the risk of major adverse cardiovascular events (MACE) and all-cause mortality. Follow-up commenced 90 days after the index date and continued until the occurrence of the study outcome or the date of the last available medical record.<br><br>RESULTS: The risk of MACE was markedly higher in the long-COVID cohort compared to the non-long-COVID cohort. The overall hazard ratio (HR) for MACE was 4.48 (95% CI: 3.95-5.07). Specific conditions such as coronary artery disease and stroke exhibited particularly high HRs, at 6.48 (5.29-7.95) and 3.46 (2.96-4.04) respectively. Mortality was significantly higher in the long-COVID group, with an HR of 1.53 (1.38-1.69).<br><br>CONCLUSIONS: Compared to patients without long COVID, patients with long COVID had a higher risk of developing MACE.},
}
@article {pmid42181509,
year = {2026},
author = {Dummer, SDC and Gonçalves, JIB and Varella, FJ and Zamin, MR and Kripka, G and Friedrich, F and Jones, MH and Centofante, GO and Colcete, FNDR and Da Costa, JC and Marinowic, DR},
title = {Impact of physical activity on cognitive function in long COVID patients: a cross-sectional observational study.},
journal = {Frontiers in sports and active living},
volume = {8},
number = {},
pages = {1738512},
pmid = {42181509},
issn = {2624-9367},
abstract = {INTRODUCTION: The COVID-19 pandemic has resulted in long-term sequelae known as long COVID, which is often characterized by cognitive dysfunctions that impair quality of life. Evidence suggests that physical activity may mitigate these impairments through neurobiological mechanisms that enhance neuroplasticity and cerebral perfusion.<br><br>OBJECTIVE: This study examined the association between physical fitness and cognitive function in individuals who had recovered from COVID-19.<br><br>METHODS: A cross-sectional observational study was conducted involving 34 adults who had been previously hospitalized for COVID-19. Cognitive performance was assessed using the Addenbrooke's Cognitive Examination-Revised (ACE-R), while cardiorespiratory fitness was evaluated through VO&#x2082; max testing. Correlation analyses and generalized linear models adjusted for age, sex, and body mass index were applied to examine associations between physical fitness and cognitive domains.<br><br>RESULTS: Participants had a mean age of 52&#x2009;&#xb1;&#x2009;12 years, a BMI of 28.7&#x2009;&#xb1;&#x2009;4.4&#x2005;kg/m[2], and a mean VO&#x2082; max of 36&#x2009;&#xb1;&#x2009;9&#x2005;mL/kg&#xb7;min&#x207b;[1]. A strong positive correlation was observed between VO&#x2082; max and the total ACE-R score (r&#x2009;=&#x2009;0.653; p&#x2009;<&#x2009;0.001), with the memory domain showing the strongest association (r&#x2009;=&#x2009;0.739; p&#x2009;<&#x2009;0.001). Higher physical activity levels, as assessed by the IPAQ, were also associated with better cognitive outcomes.<br><br>DISCUSSION: Physical fitness was significantly associated with better cognitive performance in post-COVID-19 patients. These findings support the inclusion of structured exercise programs in rehabilitation strategies to mitigate the cognitive sequelae of long COVID and underscore the importance of promoting physical activity as a public health intervention.},
}
@article {pmid42181627,
year = {2026},
author = {Maurya, N and Le, A and Melbourne, G and Chow, JSF},
title = {Long-term cardiovascular impact of COVID-19 among hospitalised and non-hospitalised populations: a narrative synthesis review.},
journal = {Frontiers in cardiovascular medicine},
volume = {13},
number = {},
pages = {1741293},
pmid = {42181627},
issn = {2297-055X},
abstract = {INTRODUCTION: COVID-19, initially recognised as a respiratory illness, affects multiple organ systems, including the cardiovascular system. Both hospitalised and non-hospitalised patients may experience persistent cardiac complications; however, the long-term impact across different levels of disease severity remains unclear. This review aims to summarise the existing evidence on the long-term cardiovascular impact of COVID-19, with a particular focus on differences between hospitalised and non-hospitalised patients.<br><br>METHOD: PubMed, MEDLINE, CINAHL, and Embase databases were searched for studies published between December 2019 and January 2024 that investigated cardiovascular outcomes in long COVID. Studies were screened for eligibility, and data were extracted using a standardised form. Due to heterogeneity across the included studies, a narrative synthesis was performed.<br><br>RESULTS: Seventy-one studies were included, most of which were observational and conducted in Europe and Asia, with follow-up periods ranging from <1 to >24 months. Hospitalised patients reported more frequent cardiovascular symptoms; however, echocardiographic abnormalities were observed across all groups. Reporting of symptom severity was inconsistent. Common cardiovascular manifestations included palpitations, chest pain, fatigue, and arrhythmias. Persistent cardiac dysfunction and dysautonomia were observed regardless of hospitalisation status.<br><br>CONCLUSION: Hospitalised patients are at higher risk of long-term cardiovascular complications, including myocardial injury, arrhythmias, and heart failure, while non-hospitalised individuals may experience subclinical cardiac changes. Vaccination appears to have a protective effect. Standardised, prospective studies are needed to clarify long-term cardiovascular risks and to guide follow-up care.},
}
@article {pmid42175169,
year = {2026},
author = {Weber, M and Knak, AK and Wulff, A},
title = {A Mobile Research App for Post-COVID Fatigue Monitoring.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {1614-1618},
doi = {10.3233/SHTI260498},
pmid = {42175169},
issn = {1879-8365},
mesh = {Humans ; *Mobile Applications ; *COVID-19/complications ; *Fatigue/diagnosis/etiology ; SARS-CoV-2 ; },
abstract = {Post-COVID fatigue is a common and burdensome symptom that fluctuates throughout the day, making it difficult to assess within clinical visits. To capture post-COVID symptom fatigue in daily settings, we developed a mobile research app based on a previous survey-based tool, designed as a progressive web application (PWA) using React. The app combines offline functionality, flexible testing times, visual instructions and local storage of participant data. The development was guided by a requirements analysis conducted through interviews with patients, identifying core needs for usability, flexibility and personalized tracking. Compared to a survey-based tool, key improvements include reduced cognitive load, a modern, minimalist design and optimization for mobile devices. Technical tests across Android and iOS devices confirmed stable and compatible performance. Future work includes a systematic usability and feasibility evaluation with both healthy participants and post-COVID patients. The application provides a flexible, user-friendly platform for symptom tracking for post-COVID studies and has potential for further development into self-management for patients.},
}
@article {pmid42170694,
year = {2026},
author = {Yenokyan, K and Wentz, E and Ni, Z and Kammerling, T and Sagona, M and DeVito, A and Mehta, SH and Lau, B and Duggal, P},
title = {Association of Comorbid and Incident Depression and Other Mental Health Conditions With Long-COVID: Results From the Johns Hopkins COVID Long Study.},
journal = {Journal of medical virology},
volume = {98},
number = {5},
pages = {e70970},
doi = {10.1002/jmv.70970},
pmid = {42170694},
issn = {1096-9071},
mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/complications/psychology ; Middle Aged ; Comorbidity ; *Depression/epidemiology ; Adult ; *Anxiety/epidemiology ; Aged ; Incidence ; Mental Health ; SARS-CoV-2 ; Mental Disorders/epidemiology ; Baltimore/epidemiology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long-term complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as long-COVID, present significant global health challenges. The factors associated with developing long-COVID remain poorly understood, especially in individuals with pre-existing comorbidities, including mental health conditions. Additionally, the relationship between persistent symptoms and incident depression and anxiety symptoms remains unclear. We analysed baseline data from 9637 participants in the Johns Hopkins COVID Long Study. Logistic regression was utilised to estimate the odds of developing long-COVID in participants with/without pre-existing mental health comorbidities (n = 3351) and incident depression and/or anxiety in participants with persistent symptoms who had only pre-existing non-mental health comorbidities (n = 3036) and those without comorbidities (n = 1781). Participants with pre-existing non-mental health comorbidities had higher odds of developing long-COVID (adjusted odds ratio (aOR) 1.47, 95% confidence interval (CI) 1.20, 1.80) compared to those without comorbidities. Participants with only mental health comorbidities showed similar elevated odds (aOR 1.49, 95% CI 1.14, 1.95). An increasing number of persistent symptoms demonstrated a strong dose-response relationship with developing incident depression and/or anxiety symptoms in both participants with only non-mental health comorbidities and those without comorbidities. Long-COVID affects individuals with and without pre-existing comorbidities; those with pre-existing comorbidities demonstrated increased odds of developing long-COVID. However, the odds among those with mental health comorbidities were not elevated beyond other comorbidities. Monitoring both physical and mental health outcomes is crucial for post-acute COVID-19 patients. Enhanced understanding of the factors associated with long-COVID is essential for improving patient care and developing effective interventions.},
}
@article {pmid42172525,
year = {2026},
author = {Bayramov, T},
title = {Stellate ganglion block for the treatment of olfactory and gustatory dysfunction in patients with long COVID-19.},
journal = {Agri : Agri (Algoloji) Dernegi'nin Yayin organidir = The journal of the Turkish Society of Algology},
volume = {38},
number = {2},
pages = {141-143},
doi = {10.5606/agri.2026.37},
pmid = {42172525},
issn = {2458-9446},
}
@article {pmid42173633,
year = {2026},
author = {Agrawal, P},
title = {AI in multi-omics analysis of COVID-19 patient data.},
journal = {Progress in molecular biology and translational science},
volume = {222},
number = {},
pages = {261-293},
doi = {10.1016/bs.pmbts.2026.01.017},
pmid = {42173633},
issn = {1878-0814},
mesh = {*COVID-19/genetics/metabolism/virology ; Humans ; *Artificial Intelligence ; *Genomics/methods ; *SARS-CoV-2 ; Metabolomics ; Proteomics ; Machine Learning ; Epigenomics ; Neural Networks, Computer ; Multiomics ; },
abstract = {The COVID-19 pandemic has led to an unprecedented increase in the volume of biological data generation, demonstrating the importance of developing an integrative and intelligent analytical framework. In the last few years, advancements in the artificial intelligence (AI) approaches have completely transformed the biological research landscape. Researchers have integrated the AI approaches with the multi-omics data generated from the COVID-19 patients to have a systems-level understanding of underlying disease mechanisms, predicting new variants and their spread rate, disease severity, immune response, and therapeutic opportunities. In this chapter, we have explored the utility of AI on multi-omics data. We started with an introduction to different kinds of omics data, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Next, we elaborated on what AI is and discussed its types, which include conventional machine learning methods (supervised and unsupervised), deep learning methods (autoencoders and convolutional neural networks), and network-based methods (graph neural networks, network propagation, and knowledge graphs). Next, we discussed different types of integration methods (early, intermediate, and late) used for integrating AI and multi-omics data. Moving ahead, we mentioned several applications of AI, such as biomarker discovery, host-pathogen interaction, drug repurposing, and predicting long COVID. Lastly, we mentioned several important projects and consortia and discussed several important case studies highlighting the usefulness of integrating AI with multi-omics data for personalized medicine.},
}
@article {pmid42173973,
year = {2026},
author = {Schwarz, J and Eicke, M and Schwedler, N and von Komorowski, G and Goldfuss, V and Fladerer, W and Barbolan, B and Mogk, M and Sommer, N},
title = {A randomized controlled trial of adjunctive speleotherapy in asthma, COPD and long COVID.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42173973},
issn = {2045-2322},
mesh = {Humans ; *Asthma/therapy/physiopathology ; Female ; Male ; *Pulmonary Disease, Chronic Obstructive/therapy/physiopathology ; *COVID-19/therapy/physiopathology ; Middle Aged ; Aged ; Quality of Life ; Respiratory Function Tests ; Treatment Outcome ; SARS-CoV-2 ; Adult ; Carbon Dioxide/blood ; },
abstract = {Speleotherapy (underground climate therapy) is a non-pharmacological intervention for chronic respiratory diseases. This randomized controlled trial investigated whether a 3-week speleotherapy course (6 sessions, 2 h/week) improves respiratory outcomes in patients on standard background therapy with asthma, COPD, or Long COVID, and whether it affects blood CO2 levels. The control group did not receive speleotherapy but continued their standard therapy. A total of 208 patients (asthma: n = 107; COPD: n = 59; Long COVID: n = 42) were enrolled across nine centers in Germany, Austria, and Italy. Assessments were conducted pre-intervention (T1), post-intervention (T2), and at 3-month follow-up (T3). Outcome measures included airway inflammation (FeNO), pulmonary function parameters (FVC% predicted values, FEV1% predicted values, FEV1/FVC, PEF% predicted values), and respiratory muscle strength (MIP and MEP in absolute values). In addition the following validated questionnaires were administered: Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Nijmegen Questionnaire (NQ), and Fatigue Assessment Scale (FAS), along with the Long COVID questionnaire from the Median Clinic Group. CO2 levels were assessed via capillary blood (SpCO2) and end-tidal CO2 (PetCO2). Between-group comparisons used the Mann-Whitney U test; within-group changes were assessed with the Wilcoxon signed-rank test (Bonferroni-Holm corrected). In patients with asthma, the predefined primary endpoint (FeNO) showed no significant improvement. In contrast, patient-reported outcomes improved significantly, with clinically relevant gains in asthma control (ACT: p < 0.001) and asthma-related quality of life (total AQLQ: p = 0.005). Lung function parameters showed statistically significant but modest improvements at T2 (FVC: p = 0.011; PEF: p = 0.010; FEV1 in participants < 70 years: p = 0.035). In patients with COPD, symptom burden improved according to CAT scores (p = 0.036), while no improvements in lung function were observed. Patients with Long COVID reported significant improvements in dysfunctional breathing (NQ: T2: p = 0.014), dyspnea (T2: p = 0.026; T3: p = 0.001), and "problems with stair climbing/muscle exertion" (T2: p = 0.042), as well as improvements in anxiety and sleep-related symptoms (T2: p = 0.021). No improvements in lung function were observed in this group. In the total cohort, the intervention group showed statistically significant improvements compared to controls in respiratory muscle strength (MIP: p = 0.002; MEP: p = 0.018) and dysfunctional breathing (NQ scores at T2: p = 0.007; T3: p = 0.017). In CO2-rich speleotherapy centers, both SpCO2 (p = 0.026) and PetCO2 (p < 0.001) increased at T2. While speleotherapy did not improve FeNO, it was associated with clinically relevant improvements in patient-reported outcomes across disease groups. Changes in lung function and respiratory muscle strength were statistically significant but modest and should be interpreted with caution. Overall, speleotherapy may have direct effects on the airways and breathing regulation, with more consistent evidence for improvements in breathing patterns than for direct effects on the airways.Trial registration: DRKS00033365 (retrospectively registered).},
}
@article {pmid42174604,
year = {2026},
author = {Watton, P and Prusty, BK},
title = {Reframing ME/CFS: toward a unified mechanistic model of chronic post-infectious diseases.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08319-3},
pmid = {42174604},
issn = {1479-5876},
abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystem illness marked by post-exertional malaise (PEM), cognitive dysfunction, autonomic disturbance, and impaired physiological resilience. Historically, the absence of validated biomarkers, heterogeneous definitions, and limited investigative capacity have complicated mechanistic interpretation and contributed to the use of psychosocial and rehabilitative frameworks in clinical practice and in parts of the literature.<br><br>MAIN BODY: Advances in systems biology, accelerated by Long-COVID research, have transformed our understanding of post-infectious syndromes, implicating persistent immune dysregulation, mitochondrial and metabolic reprogramming, endothelial and microvascular dysfunction, abnormal coagulation, lipid-mediated signalling, extracellular vesicle communication, and viral protein-associated immune activation. This review charts the shift from early post-infectious observations through psychosocial dominance to contemporary biological frameworks, emphasising that pathology is state-dependent and revealed under physiological stress.<br><br>CONCLUSION: ME/CFS is thus reframed here as a disorder of impaired adaptive capacity within post-infectious disease biology.},
}
@article {pmid42174645,
year = {2026},
author = {Plaut, S},
title = {A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08145-7},
pmid = {42174645},
issn = {1479-5876},
abstract = {BACKGROUND: The global coronavirus pandemic has led to a quiet wave of a chronic illness referred to as 'Long/Post Covid-19 syndrome' (LC) which bears a notable resemblance to functional-somatic or 'fibromyalgia-type' syndromes, and whose pathophysiology is undetermined. The lack of effective therapies for LC is straining healthcare systems worldwide and causing widespread public health and socioeconomic concerns. "Fibromyalgia" is a controversial chronic pain condition of unknown etiology largely attributed to generalized sensory hypersensitivity due to dysregulated central pain processing pathways (i.e. neuroplasting central sensitization). Despite intense research and growing attention in the scientific community, the clinical overlap of fibromyalgia, somatic symptom disorder, and post-viral chronic fatigue, is a medical puzzle yet to be solved, especially when occurring in non-severe infections and previously healthy individuals.<br><br>METHODS: This systematic scoping review covers the empirical findings on new-onset fibromyalgia manifestations after non-hospitalized covid-19. MEDLINE, Web of Science, and APA PsycINFO were searched in a systematic scoping approach for empirical studies on new-onset fibromyalgia after non-severe non-hospitalized covid-19, charting study characteristics and outcome data. A total of 228 records were included.<br><br>FINDINGS: Various types of methods, tools, and study designs are being used for LC research, with inconsistency in key concepts and definitions. This leads to a fragmented understanding of the relationship between SARS-CoV-2 infection and LC. Prevalence studies of post-Covid fibromyalgia are ongoing and susceptible to bias. The empirical evidence supports an overlap between LC, chronic fatigue syndrome, and fibromyalgia but the molecular mechanisms still remain unclear. There are conflicting findings regarding presence of viral particles, central sensitization, autoantibodies, and more.<br><br>DISCUSSION: This review highlights the need for standardized definitions and rigorous methodologies in research on LC. Future research should focus on epidemiological population-based studies with representative sampling and improving methodology, refining evolving definitions, harmonization of research, elucidating neurological mechanisms in hypothesis driven studies, and developing effective therapeutic strategies. The discussion synthesizes findings and offers an integrative mechanism for the pathophysiology of fibromyalgia and multisystem medically unexplained manifestations of LC as a non-autoimmune connective tissue disease. It helps explain neuropsychiatric and psychosomatic manifestations and is used to make testable theory-based predictions for future hypothesis-driven investigations.},
}
@article {pmid42167698,
year = {2026},
author = {Patel, A and Ryu, S and Whittington, B and Chyu, C and Chrzanowski, E and Ahmed, S and Slocum, E and Fleischer, NL},
title = {Prospective association between long COVID and COVID-related post-traumatic stress disorder among a population-based cohort of adults diagnosed with COVID-19 in Michigan.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {122009},
doi = {10.1016/j.jad.2026.122009},
pmid = {42167698},
issn = {1573-2517},
abstract = {OBJECTIVE: To better understand the mental health impacts of Long COVID, we examine the prospective association between Long COVID and risk of COVID-related post-traumatic stress disorder (PTSD) symptoms.<br><br>METHODS: We used baseline and follow-up data from the Michigan COVID-19 Recovery Surveillance Study, a population-based study of adults diagnosed with polymerase chain reaction-confirmed COVID-19 between March 2020 and May 2022 in Michigan (n&#x202f;=&#x202f;3492). Baseline data were collected a median of 4.4&#x202f;months (interquartile range (IQR): 3.4-5.7&#x202f;months) and follow-up data were collected a median of 18.4&#x202f;months (IQR: 15.0-21.3&#x202f;months) after initial COVID-19 onset. We defined Long COVID at baseline as having not recovered to usual state of health 90&#x202f;days or more after initial COVID-19 onset and having COVID-related PTSD symptoms at follow-up based on a six-item version of the PTSD Checklist for Civilians anchored to each individual's COVID-19 diagnosis. We ran modified Poisson regression models adjusting for sociodemographic characteristics, pre-existing comorbidities, COVID-19 illness severity, survey mode, and phase of the pandemic when diagnosed with COVID-19.<br><br>RESULTS: At baseline, 17.0% of adults diagnosed with COVID-19 had Long COVID, and 10.1% of adults reported COVID-related PTSD symptoms at follow-up. In the fully adjusted model, the risk of COVID-related PTSD symptoms was 2.08 times higher (95% confidence interval: 1.65-2.63) among adults with Long COVID than among adults without Long COVID.<br><br>CONCLUSION: Long COVID is prospectively associated with a higher risk of COVID-related PTSD symptoms suggesting a need to strengthen mental health screening, monitoring, and interventions among adults with this condition.},
}
@article {pmid42168400,
year = {2026},
author = {Si, Y and Zhu, X and Zhang, Y and Zhou, Z and Liu, Y and Ma, H},
title = {PANoptosis as a Therapeutic Target for COVID-19.},
journal = {Current microbiology},
volume = {83},
number = {7},
pages = {},
pmid = {42168400},
issn = {1432-0991},
support = {No.2023-CX-TD-66//the Innovation Capability Support Program of Shaanxi/ ; 82202367//the National Natural Science Foundation of China/ ; },
mesh = {Humans ; *SARS-CoV-2/drug effects ; *COVID-19/immunology/virology/pathology ; *COVID-19 Drug Treatment ; Apoptosis/drug effects ; *Necroptosis/drug effects ; Pyroptosis/drug effects ; Antiviral Agents/therapeutic use/pharmacology ; Cytokine Release Syndrome ; Animals ; },
abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has sparked a global pandemic with extensive spread, posing a severe threat to public health due to its high mortality rate in severe cases. The continuous emergence of variants with enhanced immune evasion capabilities, coupled with the prolonged and debilitating symptoms of Long Coronavirus Disease (Long COVID) such as intermittent dyspnea, persistent fatigue, and cognitive impairment (brain fog), has become a major global concern. The pathogenesis of COVID-19 is a complex interplay of direct viral cytotoxicity and an overwhelming secondary inflammatory response in the host, with the latter being a key driver of immune homeostasis disruption. Accumulating evidence indicates that PANoptosis, an integrated programmed cell death process involving the crosstalk and coordinated activation of apoptosis, pyroptosis, and necroptosis, is closely linked to the cytokine storm syndrome triggered by SARS-CoV-2 infection. As a critical mediator of various infectious diseases, PANoptosis plays a pivotal role in regulating the balance between viral clearance and pathological inflammation. This review specifically targets SARS-CoV-2, adopting a "basic mechanism-molecular regulation-therapeutic target-clinical translation" framework. We elaborate on SARS-CoV-2-induced PANoptosis mechanisms, including its constituent cell death pathways and contributions to cytokine storms. By dissecting the intricate regulatory networks between PANoptosis and interferon (IFN) signaling during viral infection, this work aims to identify potential therapeutic targets and provide novel insights for the development of effective strategies to mitigate severe COVID-19 and its long-term sequelae.},
}
@article {pmid42168930,
year = {2026},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D},
title = {Long COVID longitudinal symptoms burden clusters within a national community-based cohort.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13590-2},
pmid = {42168930},
issn = {1471-2334},
abstract = {BACKGROUND: Long COVID is clinically heterogeneous, with evolving symptom trajectories that complicate classification. Prior clustering studies often rely on Electronic Health Records data, risking underreporting. We examined longitudinal, community-based symptom clusters and associated factors.<br><br>METHODS: We analyzed CHASING COVID Cohort participants with confirmed SARS-CoV-2 infection between December 2020 and December 2022, &#x2265;&#x2009;12 months of follow-up, and long COVID (&#x2265;&#x2009;1 new symptom and concurrent activity limitation 3-12 months post-infection, both absent pre-infection). The infection in this window was the index infection; those with pre-index long COVID were excluded. Symptoms were self-reported pre-infection and at ~&#x2009;3, 6, 9, and 12 months. Missing data were handled via multiple imputation by chained equations (30 datasets). Longitudinal K-means clustering was performed within each imputed dataset, with hierarchical aggregation to derive final assignments. Logistic regression (age- and sex-adjusted) assessed associations of demographic, clinical, and social factors with cluster membership. Within the highest-burden cluster, hierarchical clustering identified symptom phenotypes.<br><br>RESULTS: Of 1,787 infected participants, 511 met criteria (22% &#x2265;50 years; 55% female; 60% White non-Hispanic; 54% mental health disorder; 7.2% immunodeficiency; 21% &#x2265;2 comorbidities). Three longitudinal clusters emerged: highest, moderate, and lowest burden. The highest-burden cluster showed persistent multisystem symptoms (median 6 symptoms at 6-9 months) with frequent fatigue, concentration difficulty, post-exertional malaise, myalgia, sleep disturbance, gastrointestinal symptoms, headache, irritability, and mobility limitations. The moderate cluster peaked at 3 symptoms, while the lowest remained at 1 symptom. Older age (aOR 2.68, 95% CI 1.59-4.53), female sex (2.36, 1.48-3.76), mental health disorder (2.65, 1.65-4.25), and immunodeficiency (4.23, 1.71-10.51) were associated with highest vs. lowest burden. Within the highest-burden cluster, three phenotypes emerged: multisystemic dysfunction, psychiatric/neurological dysfunction, and physical/respiratory dysfunction.<br><br>CONCLUSIONS: Distinct long COVID clusters and phenotypes underscore heterogeneity and support tailored management and risk stratification.},
}
@article {pmid42170596,
year = {2026},
author = {Philippot, Q and Debray, MP and Guyard, A and Achkar, A and Le Voyer, T and Le Hingrat, Q and Crestani, B and Borie, R},
title = {Good? A very long COVID-19.},
journal = {Journal of human immunity},
volume = {2},
number = {1},
pages = {e20250178},
pmid = {42170596},
issn = {3065-8993},
abstract = {We report a case of chronic SARS-CoV-2 infection resulting from impaired B cell-mediated immunity to SARS-CoV-2 in a patient with Good syndrome. Immunoglobulin replacement therapy alone was sufficient to achieve clinical and radiological resolution.},
}
@article {pmid42158877,
year = {2026},
author = {Sanhueza, S and Cabrera, C and Quiroga, R and Antilef, B and Muñoz, C and Vera, A and Cartes, R and Lamperti, L and Guzmán-Gutiérrez, E and Aguayo, C and Ormazábal, V and Hernández, MA and Lastra, J and Riffo, B and Cerda, G and Ferrada, L and De Gonzalo-Calvo, D and García-Hidalgo, MC and Henríquez, M and Barría, MI and Verdugo, RA and Colombo, A and Labarca, G and Nova-Lamperti, E},
title = {De novo COVID-19-associated insulin resistance drives dysregulated neutrophil extracellular trap formation (NETosis) four months after infection.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1787799},
pmid = {42158877},
issn = {1664-3224},
mesh = {Humans ; *Extracellular Traps/immunology/metabolism ; *COVID-19/immunology/complications ; Male ; Female ; Middle Aged ; *Insulin Resistance/immunology ; *SARS-CoV-2/immunology ; *Neutrophils/immunology/metabolism ; Aged ; Adult ; },
abstract = {BACKGROUND: Glucose metabolism disorders (GMDs) are established risk factors for severe COVID-19, but increasing evidence indicates that they may also develop de novo after SARS-CoV-2 infection. Neutrophil extracellular trap formation (NETosis) plays a central role in immunothrombosis, and because neutrophils rely predominantly on glycolysis, they are particularly sensitive to systemic metabolic disturbances. However, the impact of post-COVID-19 GMDs on NETosis remains poorly understood. This study aimed to characterize the emergence of GMDs after COVID-19 and to determine their effect on neutrophil NETosis.<br><br>METHODS: Sixty COVID-19 patients were stratified according to the presence or absence of GMDs before infection and at four months post-infection. Demographic, clinical, metabolic, and inflammatory parameters were assessed. Vital NETosis was quantified by flow cytometry. In addition, the capacity of patient plasma to induce NETosis was evaluated using live-cell imaging of healthy neutrophils as biosensors.<br><br>RESULTS: Among patients without pre-existing GMDs, 24 of 36 developed insulin resistance (IR) four months after COVID-19. Neutrophils from these patients exhibited increased basal NETosis but showed impaired NETosis in response to TLR7/8 agonists, key sensors of viral single-stranded RNA, compared with control groups. In contrast, NETosis responses to IL-6 and TNF-&#x3b1; were preserved, excluding an intrinsic neutrophil defect. Plasma from IR patients significantly enhanced NETosis, and in vitro experiments demonstrated that insulin enhances NETosis independently of glucose concentrations.<br><br>DISCUSSION: De novo IR following COVID-19 dysregulates NETosis primarily through an insulin-enhancing effect. Post-viral control of glucose metabolism disorders may be critical to limit pathological NETosis and its thrombo-inflammatory consequences.},
}
@article {pmid42159650,
year = {2026},
author = {Ortega-Martin, E and Alvarez-Galvez, J},
title = {Development of the long COVID - 6 dimensions quality of life (LC-6D-QoL) scale: a Delphi study.},
journal = {Journal of patient-reported outcomes},
volume = {},
number = {},
pages = {},
doi = {10.1186/s41687-026-01084-3},
pmid = {42159650},
issn = {2509-8020},
abstract = {BACKGROUND: Long COVID significantly impairs quality of life through multi-systemic complexity, including fatigue, cognitive dysfunction, and dysautonomia. Existing generic tools fail to capture these manifestations, limiting patient-centered assessment. To address this gap, this study proposed a patient-focused, 16-item scale developed and content-refined through expert consensus, to evaluate quality of life in people with Long COVID.<br><br>METHODS: A two-round Delphi study involved two rounds of questionnaires and feedback. 37 experts with clinical or research experience in Long COVID participated in the first round, and 26 completed the second. In the first round, experts rated the relevance of proposed indicators. The second questionnaire incorporated modifications based on the experts' comments. Quantitative data were analyzed using descriptive statistics and agreement measures, while qualitative comments were thematically coded.<br><br>RESULTS: Experts reached substantial agreement, above 83%, on the dimensions covering the main aspects of quality of life. Based on participants' comments, the initial scale was modified, and a consensus between 80 and 92% was reached in all dimensions. The Delphi process resulted in a scale composed of 6 dimensions and 16 items, which include dysautonomia assessment and affective-sexual life impact, omitted in generic tools. The dimensions of the LC-6D-QoL Scale were: (1) general health; (2) physical health; (3) mental health; (4) daily functioning; (5) social relationships and support; and (6) economic and work-related aspects.<br><br>CONCLUSIONS: This study establishes an expert-informed foundation for future validation of the LC-6D-QoL Scale, integrating clinical and experiential knowledge to refine its preliminary structure. The LC-6D-QoL Scale is a patient-centered instrument capturing six key dimensions often missed in generic tools-such as dysautonomia, mental fatigue, and work-related impact-to better assess quality of life in Long COVID.},
}
@article {pmid42160940,
year = {2026},
author = {Spedding, M and Aerts, J and Alexander, S and Bellozzi Woestelandt, AG and Chiricozzi, E and Henriques, A and Lledo, PM and Loeffler, JP and Perera, R and Platt, FM and Pradat, PF and Rene, F and Schapira, A and St Clair, L and Talbot, K and Taquet, M and Toborek, M and Turner, B and Zandi, M and Gressens, P},
title = {Erratum to "Links between COVID-19, long COVID, and neurodegeneration: The role of glycosphingolipids" [Pharmacological Reviews 78 (2026) 100113].},
journal = {Pharmacological reviews},
volume = {78},
number = {4},
pages = {100142},
doi = {10.1016/j.pharmr.2026.100142},
pmid = {42160940},
issn = {1521-0081},
}
@article {pmid42162520,
year = {2026},
author = {Rivelli, A and Ording, J and Sheehan, J and Hirschtick, JL},
title = {Demographic Differences in Long COVID Diagnosis Across Levels of Care: Implications for Clinical Practice.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {42162520},
issn = {1525-1497},
abstract = {BACKGROUND: Long COVID is a novel condition primarily studied in outpatient settings, failing to capture the full spectrum of affected patients, particularly those from disadvantaged populations. Demographic differences in the medical encounter setting of initial long COVID diagnosis suggest disparities in symptom severity, care access, and utilization.<br><br>OBJECTIVE: To identify demographic factors associated with the encounter setting at initial long COVID diagnosis.<br><br>DESIGN: Retrospective study utilizing data from the electronic medical record within the largest Midwestern non-profit healthcare system.<br><br>PATIENTS: In total, 8008 patients aged 18+&#x2009;with initial long COVID diagnosis (ICD-10 U09.9) between March 1, 2020, and October 31, 2023.<br><br>MAIN MEASURES: Demographic factors (age, sex, race/ethnicity, insurance, median household income) and encounter setting at first long COVID diagnosis were extracted. We used multinomial logistic regression to estimate adjusted odds of encounter setting at first diagnosis by demographic subgroup.<br><br>KEY RESULTS: Patients were most frequently diagnosed with long COVID in an outpatient non-diagnostic encounter (92%), followed by emergency (3%), outpatient diagnostic (e.g., following laboratory or imaging; 3%), and inpatient (2%). After mutually adjusting for all demographic factors, relative to first long COVID diagnosis in the outpatient non-diagnostic setting, older age was associated with higher odds of first diagnosis in outpatient diagnostic and inpatient settings but lower odds in the emergency setting. Greater median household income was associated with higher odds of first diagnosis in the outpatient diagnostic setting but lower odds in the emergency setting. Patients with Medicaid had lower odds of first diagnosis in the outpatient diagnostic setting but 3.0 times higher odds in emergency settings.<br><br>CONCLUSIONS: Patients with lower socioeconomic status indicators had increased odds of first long COVID diagnosis in higher acuity settings, suggesting potential differences in symptom severity, access, and care-seeking behaviors. Long COVID research and education should target patients and providers in these settings.},
}
@article {pmid42163148,
year = {2026},
author = {Ghosal, R and Gronowski, B and Fish, D and Rinaldi, JB and Vartanian, K},
title = {A mixed-methods study comparing clinical and patient-reported perspectives on long COVID: insights from electronic health records and narrative journal entries.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13593-z},
pmid = {42163148},
issn = {1471-2334},
abstract = {BACKGROUND: Many studies of Long COVID have used a variety of clinical and self-reported data to characterize this condition. Previous research has shown the many ways in which these two types of data sources can differ. Our study aims to expand on previous research by exploring descriptions of Long COVID using electronic health records (EHRs) and narrative journal entries collected from the same patients to understand how they align and differ.<br><br>METHODS: This convergent mixed methods observational study design analyzed narrative patient-reported data (journal entries) and EHRs from adults with a clinical Long COVID diagnosis. From August 2020 to July 2023, adults across seven states who tested positive for COVID-19 were invited to participate in My COVID Diary (MCD) for up to a year; in 2023 they re-consented for EHR access. Of 18,941 MCD participants, 3,323 consented to EHR access (17.54% participation rate). Inclusion required at least one medical encounter and one journal entry between 4 and 52 weeks post-infection, plus an EHR-recorded Long COVID diagnosis. Ninety-two individuals met all criteria. EHR was used to descriptively analyze patient demographics, medical encounters, and diagnoses. MCD journal entries were coded and analyzed using a framework analysis to identify themes. Ten individuals with journal entries within 1 week of a clinical visit were randomly selected and the records were manually reviewed for semantic overlap to qualitatively illustrate alignment.<br><br>RESULTS: The most frequent types of medical encounters for participants in the study window were outpatient primary care or specialist visits. The most common diagnoses found in the EHR were respiratory conditions, joint pain, cardiovascular issues, malaise and fatigue, and ear, nose, and throat issues. Journal entries highlighted similar symptoms like tiredness/fatigue, pain, respiratory challenges, mental health concerns, and cardiovascular issues. Key differences were that journal entries had a greater emphasis on more subjective or functional symptoms and experiences such as fatigue, brain fog, and mental health and included the impact of long COVID on daily, work, and social activities. Comparison of co-occurring EHR and journal entries for individual encounters illustrated limited to no overlap in symptom description for the 10 selected cases.<br><br>CONCLUSIONS: While our study is limited by a small sample size that impacts generalizability, our in-depth review of these data sources indicates that neither EHR nor patient-reported data alone conveys the complete experience of Long COVID. Integration of patient-reported and EHR data is likely needed to fully understand and treat patients struggling with Long COVID.},
}
@article {pmid42163696,
year = {2026},
author = {Seneff, S and Nigh, G and Kyriakopoulos, AM},
title = {Melatonin in Health and Disease and its Metabolism by the Gut Microbes: Implications for Deuterium Homeostasis?.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673468554260508041733},
pmid = {42163696},
issn = {1875-533X},
abstract = {Deuterium (2H), a heavy isotope of protium (1H), is a naturally occurring element with a significant impact on human metabolism. Despite its natural presence, deuterium can impair mitochondrial function by damaging ATPase pumps; consequently, biological organisms have evolved sophisticated strategies to mitigate the risks of deuterium overload and protect mitochondrial integrity. Multiple enzymes have evolved to prefer hydrogen over deuterium in their reactions to protect these pumps. One class of enzymes is the cytochrome P450 (CYP) enzymes, which oxidize many substrates, mainly in the Endoplasmic Reticulum (ER), often producing water as a by-product. Furthermore, hydrogen peroxide (H2O2), produced in the ER by ERO1, can travel via the cytoplasm to the mitochondria, where it is reduced to two molecules of water via glutathione peroxidase. Melatonin is an ancient antioxidant molecule that first appeared in photosynthetic bacteria billions of years ago to protect against oxygen produced by respiration. In this paper, we present a hypothesis that melatonin metabolism in the gut provides deuterium- depleted protons to the enterocyte mitochondria. Few are aware that melatonin, known mainly as the hormone produced by the pineal gland to regulate circadian rhythms, is produced in the gut at 400 times the amount produced by the pineal gland. In the gut lining, melatonin is synthesized from N-acetylserotonin through the addition of a methyl group from S-adenosylmethionine. This methyl group, which we argue is severely deuterium-depleted due to its gut microbial source, is then fully metabolized by CYP2C19 in the ER of enterocytes in the small intestine, producing four molecules of water, which we argue would also be depleted in deuterium. Melatonin is recycled from the gut to the liver multiple times via the bile acids, and it is repeatedly converted back to N-acetylserotonin and regenerated, each time producing four water molecules derived from its methyl group. Butyrate, another nutrient supplied by gut microbes, stimulates the synthesis of serotonin and melatonin from tryptophan in the gut. Melatonin is a powerful antioxidant in mitochondria and promotes a healthy microbiome. Melatonin deficiency is associated with the severity of long COVID, and melatonin supplementation can help minimize side effects.},
}
@article {pmid42163969,
year = {2026},
author = {Hendriks, S and Grady, C and Fitzgerald, ML and Gross, RS and Maughan, C and Peluso, MJ and Varma, S and Nath, A and Rid, A},
title = {The next phase in Long COVID research: addressing the ethical challenges in trials of disease-modifying treatments.},
journal = {EClinicalMedicine},
volume = {95},
number = {},
pages = {103918},
pmid = {42163969},
issn = {2589-5370},
abstract = {Almost five years after COVID-19 emerged, multiple scientific uncertainties remain about why some people experience ongoing symptoms long after being infected with SARS-CoV-2 (Long COVID). The pathophysiology underlying Long COVID and its potential to represent several endotypes are still under investigation. These scientific uncertainties around Long COVID have been cited as a reason to delay treatment trials until the disease is better understood. In this paper, a group of bioethicists, clinician-scientists and people with lived experience with Long COVID argue that it is ethically imperative to conduct trials of disease-modifying treatments for Long COVID now. Furthermore, we argue that although conducting such trials can pose ethical challenges, these challenges can be overcome through careful research priority-setting, rigorous trial design, fair participant selection, and ensuring that the risk-benefit profile is favorable.},
}
@article {pmid42153547,
year = {2026},
author = {Freitas, RDS and Garcia, ALH and Martins, BAA and Dalberto, D and Da Silva, FR and Borges, MS and Peralta, GEP and Bobermin, LD and Quincozes-Santos, A and Da Silva, J},
title = {Ultra-Processed Foods and Diet Quality in Long COVID: Associations with Symptom Burden, DNA Damage, and Inflammation.},
journal = {Mutagenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/mutage/geag020},
pmid = {42153547},
issn = {1464-3804},
abstract = {Diet quality can be a potential modifier of post-acute COVID-19 syndrome (PACS), yet the relationship between dietary patterns, symptom burden, and biological markers remains poorly understood. We hypothesized that a low-quality diet would positively associate with PACS symptom burden, DNA damage, inflammatory and neurotrophic markers, and with overall health quality. 186 individuals were classified into three groups: control (n = 64), acute PACS (n = 66), and chronic PACS (n = 55). Dietary intake was assessed by a food frequency questionnaire (FFQ), and diet quality was quantified via the Protective and Risk Eating Score (PRES). Blood samples were analyzed for inflammatory (TNF-α, TGF-β, IL-6, IL-1β) and neurotrophic (BDNF, GDNF, S100B) markers. DNA damage was assessed by micronuclei frequency, telomere length, and comet assay parameters. Health index (HI) was assessed by daily habits (alcohol consumption, sleeping patterns, hydration, exercise frequency, smoking habits, anthropometric parameters, and PRES). No significant differences were found among groups in ultra-processed foods (UPF) or sugary products intake, PRES scores, inflammatory or neurotrophic biomarkers, DNA damage indicators, and HI. Of note, poorer diet quality was associated with higher symptom burden in PACS women, mainly in fatigue, memory, mental health, circulatory, and skin symptom domains. Few associations among diet quality, HI, and biomarkers emerged. Of note, principal component analysis shows that PACS relies on the convergence of genomic instability, systemic inflammation, and low diet quality. These findings suggest that diet may represent a modifiable factor in PACS management, warranting longitudinal and interventional studies to determine causality and therapeutic potential.},
}
@article {pmid42156850,
year = {2026},
author = {Peter, RS and Nieters, A and Sedelmaier, L and Kräusslich, HG and Brockmann, SO and Göpel, S and Merle, U and Steinacker, JM and Rothenbacher, D and Kern, WV and , },
title = {Population-based comparison of post-acute sequelae of COVID-19 and health-related quality of life across pandemic periods: Omicron era versus early pandemic.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42156850},
issn = {2045-2322},
mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology/complications ; Adult ; Male ; Middle Aged ; Female ; Aged ; Adolescent ; SARS-CoV-2/isolation &amp; purification ; Young Adult ; Post-Acute COVID-19 Syndrome ; Pandemics ; Prevalence ; Surveys and Questionnaires ; Germany/epidemiology ; },
abstract = {Post-COVID-19 syndrome (PCS) may vary across pandemic phases. We compared the prevalence of post-acute COVID-19 symptom clusters following SARS-CoV-2 infection in the early pandemic and during the Omicron era using a population-based approach. The EPILOC study enrolled individuals aged 18-65 years who tested PCR-positive for SARS-CoV-2 during the early pandemic, between October 2020 and April 2021, in defined geographic regions within Baden-Württemberg. EPILOC-Omicron used an identical design for individuals infected between June and July 2022. Participants completed a standardised questionnaire assessing sociodemographics, lifestyle, symptoms, and health-related quality of life (SF-12). PCS was defined as ≤ 80% recovery of general health or work capacity plus at least one new moderate-to-strong symptom, both compared to before index infection. Generalised linear models adjusted for age, sex, and education were used to estimate relative risks (RRs). We analysed data from 11,710 EPILOC (24% response) and 12,560 EPILOC-Omicron participants (17% response). Participants were similar in age and sex distribution. Vaccination before infection differed markedly (< 3 vs. > 92%). PCS prevalence was 29.6% in EPILOC and 14.5% in EPILOC-Omicron. Predictors of PCS were similar for both. Symptom clusters were consistently less frequent after infection during the Omicron era (e.g., fatigue RR = 0.54; neurocognitive impairment RR = 0.53; chest symptoms RR = 0.47; smell/taste disorder RR = 0.17). Health-related quality of life was similar in PCS cases of both cohorts (mean SF-12Physical 40.3 vs. 41.0, mean SF-12Mental 38.9 vs. 40.7). PCS was less common following SARS-CoV-2 infection in the Omicron era compared to the early pandemic period. However, affected individuals continue to experience substantial, comparable impairment in hrQoL across both pandemic periods.},
}
@article {pmid42157207,
year = {2026},
author = {Dhir-Hewitt, E and Newlands, F and Shafran, R and Stephenson, T and Richards-Belle, A and Dalrymple, E and Chalder, T and Ford, T and Fox-Smith, L and Heyman, I and N Ladhani, S and G Semple, M and Segal, TY and Swann, O and Whittaker, E and , and Pinto Pereira, SM},
title = {Exploring post-Covid-19 condition in children and young people 3.5 years after infection: a mixed-methods analysis from the CLoCk study.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-27520-z},
pmid = {42157207},
issn = {1471-2458},
support = {ES/T00200X/1//ESRC-BBSRC Soc-B Centre for Doctoral Training/ ; MR/Y009398/1//UK Medical Research Council Senior Non-clinical fellowship/ ; },
abstract = {BACKGROUND: Comprehensive data on the persistence of Post-COVID-19 Condition (PCC; also known as Long COVID) and its impact on children and young people (CYP), incorporating their own perspective, is crucial to enhance our understanding of the condition, improve service provision and inform clinical management.<br><br>METHODS: We examine long-term symptoms, health, and well-being among CYP persistently meeting PCC criteria up to 3.5-years after SARS-CoV-2 infection (when they were aged between 11-to-17-years), using a mixed-methods approach. 68 CYP from the CLoCk study who persistently met PCC criteria at 3- (April-June 2021), 6- (July-September 2021), 12- (January-March 2022), and 24-months (January-March 2023) post-infection were invited to complete an additional follow-up (October-November 2024). The survey assessed current symptoms and health status using validated measures, and symptom experiences through open-text responses. Quantitative data were analysed descriptively; qualitative data were analysed using thematic framework analysis. Findings were integrated using a convergent parallel design.<br><br>RESULTS: 50 CYP completed the survey; of these 42 (84%) responders continued to meet the PCC definition 3.5-years post-infection. All 42 (100%) reported tiredness and 34 (81%) reported 5&#x2009;+&#x2009;symptoms 3.5-years post-infection. Qualitative analysis reinforced tiredness as a central symptom, alongside co-occurring symptoms that impact daily life. While quantitative and qualitative findings largely converged, context as to why CYP reported high levels of impact were only available from qualitative data.<br><br>CONCLUSIONS: CYP with PCC persisting for 3.5-years post-infection experience multiple symptoms of wide-ranging severity and disruption to daily life, education and social participation.},
}
@article {pmid42158498,
year = {2026},
author = {Kaleem, S and Sawano, M and Krumholz, HM},
title = {Ocular Symptoms in Long COVID: A Cross-Sectional Study [Response to Letter].},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {620572},
pmid = {42158498},
issn = {1177-5467},
}
@article {pmid42119916,
year = {2026},
author = {Swanson, JM},
title = {Editorial: Fetal Exposure to Maternal Infection by SARS-CoV-2 and Effects on Child Neurodevelopment.},
journal = {Journal of the American Academy of Child and Adolescent Psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaac.2026.04.016},
pmid = {42119916},
issn = {1527-5418},
abstract = {The systematic review and meta-analysis by Rizzo et al.[1] should be of interest to child psychiatrists and pediatricians based on its historical and contemporary relevance (Table 1[2-9]). Historically, it addresses the 2019 COVID-19 pandemic-so far the most devastating health-related event of the 21[st] century-which may haunt us for decades because of post-acute sequelae of SARS-CoV-2 (PASC) or Long-COVID, which is now affecting millions of individuals. Contemporarily, it addresses an unresolved issue regarding neurodevelopment in children with a history of fetal exposure to SARS-CoV-2 during pregnancy (presumably uninfected, because vertical transmission is rare), as well as a contentious public debate regarding outcomes of children with fetal and childhood exposure to COVID-19 vaccinations. For this review, the authors applied both a narrow approach (by restricting the review to studies of neurodevelopment in children) and a broad approach (by including studies with "neurodevelopmental outcomes of the child at any age" and "any available measure of child development"). They did the following: (1) identified studies that met the exposure criteria (ie, maternal infection or vaccination) for the review ("70 studies" with 88 neurodevelopmental outcomes); (2) described basic characteristics and findings of all studies in an informative table ("which summarizes methodologies, key findings, and covariates adjustments"); (3) presented structured narrative syntheses for the studies classified into 7 outcome subdomains (with "… consistency [defined] as >70% of studies within a domain reporting effects in the same direction"): and (4) conducted meta-analyses for multiple studies with dichotomous outcomes (based on "…the number of individuals screening positive versus negative for specific auditory or developmental concerns"). As outlined in Table 1, the narrative syntheses suggested reassurances that fetal exposure did not disrupt neurodevelopment (because adverse effects of were not consistent across studies for any outcome domain), but the authors did not accept the null hypothesis (even though it was consistent with their own research). Instead, they conducted meta-analyses that suggested that there may be cause for concern (given that adverse effects were statistically significant for an initial neonatal auditory test and for some ratings of neurodevelopment).},
}
@article {pmid42149980,
year = {2026},
author = {Shoshina, II and Fernandes, TP and Santos, NA and Dahlgren, LN},
title = {Divergent Long-Term Recovery After Long COVID in Tobacco Use Disorder and Healthy Controls: A Longitudinal Study.},
journal = {Nicotine &amp; tobacco research : official journal of the Society for Research on Nicotine and Tobacco},
volume = {},
number = {},
pages = {},
doi = {10.1093/ntr/ntag112},
pmid = {42149980},
issn = {1469-994X},
abstract = {INTRODUCTION: Although tobacco use disorder (TUD) and long COVID (LC) have been associated to neuropsychiatric disturbances, it remains unclear how tobacco dependence affects the recovery of clinical, cognitive, and biological processes over time.<br><br>METHODS: This study compared individuals with tobacco use disorder and healthy controls using longitudinal assessments from pre-infection baseline through two post-COVID follow-ups over 12 months. Comprehensive assessments covered clinical, neuropsychiatric, and cognitive functioning, tobacco dependence and exposure, and peripheral biomarkers reflecting neuroendocrine regulation, inflammation, neuroplasticity-related processes, and nicotine metabolism relevant to post-COVID recovery.<br><br>RESULTS: Both groups exhibited marked clinical, cognitive, and biological alterations following LC; however, recovery trajectories diverged over time. Healthy controls showed clear improvement by 12 months, whereas individuals with TUD showed persistent impairment across clinical and cognitive functioning. Cognitive performance recovered in controls but remained reduced in the TUD group. Biological trajectories paralleled clinical recovery patterns. Dimensional analyses identified two latent components reflecting neuropsychiatric and inflammatory-neurobiological processes. Within the TUD group, two recovery-related phenotypes emerged: a persistently impaired subgroup and an adaptive subgroup showing partial recovery.<br><br>CONCLUSIONS: Tobacco use disorder is associated with impaired and incomplete clinical and biological recovery following long COVID, beyond smoking exposure alone. These findings emphasize the need for post-COVID care models that integrate tobacco dependence with recovery-related clinical and biological processes, supporting sustained recovery and cessation outcomes.},
}
@article {pmid42151044,
year = {2026},
author = {Pan, LC and Lin, YH and Liu, YH and Chiang, CY and Chen, JY and Lee, HS and Fang, YY},
title = {[Developing and Validating the Long COVID-19 Symptom Severity Index (LCSSI) for Patients With Chronic Obstructive Pulmonary Disease].},
journal = {Hu li za zhi The journal of nursing},
volume = {73},
number = {3},
pages = {},
doi = {10.6224/JN.26306},
pmid = {42151044},
issn = {0047-262X},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/physiopathology ; *COVID-19/complications ; Male ; *Severity of Illness Index ; Female ; Cross-Sectional Studies ; Middle Aged ; Aged ; },
abstract = {BACKGROUND: Existing tools for assessing Long COVID are primarily designed for the general population. Few instruments adequately capture the needs and vulnerabilities of high-risk groups such as patients with chronic obstructive pulmonary disease (COPD), who have structurally vulnerable lungs.<br><br>PURPOSE: This study was designed to develop and validate the Long COVID Symptom Severity Index (LCSSI), a concise and clinically sensitive instrument designed specifically for use on patients with respiratory diseases.<br><br>METHODS: The study was conducted in two phases. In Phase I, item generation was based on a literature review and expert panel discussion involving six pulmonologists. In Phase II, a cross-sectional validation study was conducted in the chest medicine wards and outpatient clinics of a medical center in southern Taiwan. The psychometric properties of the LCSSI were examined.<br><br>RESULTS: One hundred and twenty-eight patients with COPD (93% male) were enrolled, of whom 63.3% were classified under GOLD (global initiative for chronic obstructive lung disease) Group E. The most prevalent symptoms found were cough/sputum (100%), fatigue/weakness (90.6%), and dyspnea (88.3%). The LCSSI demonstrated excellent internal consistency (Cronbach's &#x3b1; = .88), and correlated positively with the COPD Assessment Test (p < .01) and negatively with the 15D Health-Related Quality of Life scale (p < .01). Mean LCSSI scores differed significantly across GOLD groups, with Group E showing higher mean total and core symptom scores (all p < .01), supporting construct validity.<br><br>Based on this sample, the results indicate the LCSSI has acceptable internal consistency and validity, supporting its use as a reference tool for symptom assessment in patients with COPD during the late recovery phase for Long COVID.},
}
@article {pmid42152441,
year = {2026},
author = {Luo, S and Zheng, Z and Karimi, L and Plebanski, M and Anderson, KLM and Jovanovski, N and Lankatillake, C and Cockshaw, W and Wollersheim, D and Sheahan, J and Seal, EL and Butler-Henderson, K and Campbell, D and Clarke, A and Cleary, S and Danaher, J and El-Ansary, D and Figueiredo, B and Flanagan, KL and Hines, C and Jessup, RL and Mehmet, H and Miller, SM and Seeley, MC and Sivan, M and Smarrelli, F and Smith, AB and Vesty, G and Vindigni, D and Xenos, S and Stocco, L and Hartman, S and Ivory, I and Itsiopoulos, C},
title = {Impact of long COVID on diverse Australian populations: a multi-site, longitudinal prospective cohort study protocol.},
journal = {BMJ open},
volume = {16},
number = {5},
pages = {e114928},
doi = {10.1136/bmjopen-2025-114928},
pmid = {42152441},
issn = {2044-6055},
mesh = {Humans ; Australia/epidemiology ; *COVID-19/psychology/epidemiology/complications ; Longitudinal Studies ; Prospective Studies ; SARS-CoV-2 ; Adult ; Psychometrics ; Surveys and Questionnaires ; Research Design ; Post-Acute COVID-19 Syndrome ; Chronic Disease ; Female ; Multicenter Studies as Topic ; Male ; },
abstract = {BACKGROUND: Long COVID is a complex, multisystem chronic condition that may persist or fluctuate for months to years after SARS-CoV-2 infection. Despite emerging international research, significant gaps remain in understanding the full breadth of long COVID's impacts in Australia. No study has yet prospectively examined these multidimensional impacts using a culturally appropriate, user-validated toolkit. Our study aims to characterise symptom profiles, functional outcomes and psychological, social, financial and behavioural impacts of long COVID in Australian adults; identify factors associated with recovery trajectories; and validate a set of measures to support research and clinical care.<br><br>METHODS: This national, multi-site, longitudinal prospective cohort study comprises three phases: (1) survey selection and user-testing; (2) psychometric validation; and (3) a longitudinal cohort study. Survey selection was informed by literature review, Australian parliament inquiry reports and international recommendations, and refined through iterative user-testing and expert review. A total of 1000 participants aged &#x2265;18 years from diverse cultural backgrounds with ongoing symptoms following COVID-19 infection will be divided into three cohorts based on time since infection. Surveys will be administered at seven time points over 24 months, with optional follow-up to 36 months. Data linkage to state and national health datasets will enable an objective assessment of healthcare utilisation and associated costs. Psychometric properties of the tools will be evaluated using baseline responses from the initial 300 participants, including assessments of structural/construct validity, convergent validity, known-groups validity, cross-validity, internal reliability, responsiveness and test-retest reliability. Other data analyses will include descriptive statistics, repeated-measures analysis of variance, linear mixed-effects modelling and multivariable regression models.<br><br>ETHICS AND DISSEMINATION: Ethics approval was obtained from The St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC) (112108/2024/PID00364) and RMIT University HREC (28124). Research findings will be disseminated at conferences and in peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12625001415493).},
}
@article {pmid42152450,
year = {2026},
author = {Boutry, C and Phillips, J and Knight, C and Holmes, J and Patel, P and Morriss, R and das Nair, R and Douglas, E and Bolton, CE and Guo, B and Radford, K},
title = {Developing a job retention vocational rehabilitation intervention for people with long covid: a person-based approach.},
journal = {BMJ open},
volume = {16},
number = {5},
pages = {e109740},
doi = {10.1136/bmjopen-2025-109740},
pmid = {42152450},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/rehabilitation/complications/psychology ; *Return to Work ; *Rehabilitation, Vocational/methods ; SARS-CoV-2 ; Male ; Female ; Middle Aged ; Adult ; Fatigue/rehabilitation ; Job Security ; },
abstract = {BACKGROUND: Long covid affects a significant proportion of people following SARS-CoV-2 infection and is associated with persistent symptoms such as fatigue, cognitive dysfunction and breathlessness which can negatively impact a person's ability to return to and remain in work. Although tiered vocational rehabilitation (VR) models have been proposed, these are often generic, lack empirical validation and may not address the complex, fluctuating needs of this population.<br><br>OBJECTIVES: To co-design a VR intervention (the COVID-19-VR intervention) to support return to work (RTW) for people with long covid (pwLC).<br><br>SETTING: Primary and secondary care.<br><br>DESIGN: Mixed-methods target population-centred, person-based approach in three stages: Stage 1: interviews (n=21) with pwLC to identify issues and challenges faced in working with long covid. Stage 2: three co-design workshops with pwLC and service providers to (a) generate guiding principles, (b) identify key intervention features to address work needs, (c) create a logic model to illustrate how the intervention could work and (d) develop a treatment plan and resources. Stage 3: feasibility and acceptability testing in six cases (three critical care admissions, three primary care referrals).<br><br>RESULTS: PwLC described work-related problems relating to: fluctuating symptoms (cognition, fatigue and breathlessness), employer, coworker and family's understanding of long covid and workplace adjustments. We developed a 6-session, 12-week individually tailored, remotely delivered intervention that included vocational goal setting, RTW planning, fatigue/symptom management, financial advice, and where permitted, education for family/employers, employer engagement and negotiation of a phased RTW. Following feasibility testing, changes included accommodating the long-term nature of long covid, addressing unmet psychological needs, and adding content on adjustment, processing traumatic experience and performance/symptom anxiety, with extended delivery including monitoring, review and case coordination.<br><br>CONCLUSIONS: PwLC may need specialist help to RTW. Our COVID-19-VR appears feasible and acceptable and warrants further evaluation using a staged approach, prior to any definitive effectiveness trial.},
}
@article {pmid42152584,
year = {2026},
author = {Hori, M and Hayama-Terada, M and Kitamura, A and Hosozawa, M and Muto, Y and Iba, A and Takayama, Y and Kimura, T and Iso, H},
title = {Prevalence and Risk Factors for Persistent Post-COVID-19 Condition at 3, 6, 12, and 18 Months After Initial Infection Among Adults Living in a Community of Japan: Yao COVID-19 Study.},
journal = {Journal of medical virology},
volume = {98},
number = {5},
pages = {e70973},
doi = {10.1002/jmv.70973},
pmid = {42152584},
issn = {1096-9071},
support = {JPMH21HA2011//MHLW Research on Emerging and Re-Emerging Infectious Diseases and Immunization/ ; JPMH23HA2011//MHLW Research on Emerging and Re-Emerging Infectious Diseases and Immunization/ ; JPMH24HA2015//MHLW Research on Emerging and Re-Emerging Infectious Diseases and Immunization/ ; JPMH25HA2005//MHLW Research on Emerging and Re-Emerging Infectious Diseases and Immunization/ ; },
mesh = {Humans ; Female ; Adult ; Middle Aged ; Male ; Japan/epidemiology ; *COVID-19/epidemiology/complications ; Risk Factors ; Prevalence ; Aged ; Prospective Studies ; Young Adult ; Adolescent ; SARS-CoV-2 ; Comorbidity ; },
abstract = {The risk factors for long-term persistent post-coronavirus disease (COVID-19) condition (PCC) years after infection remain unclear. In this study, we investigated the prevalence of PCC and the associated risk factors after severe acute respiratory syndrome coronavirus 2 infection in the general population. This prospective cohort study included individuals aged 18-79 years diagnosed with COVID-19 between March 2021 and April 2022 and matched non-infected individuals living in Yao City, Japan. Baseline and follow-up surveys were conducted in 2022 and 2024, respectively. PCC was defined as symptoms persisting for ≥2 months at 3 months post-infection. Among 7404 eligible individuals, 3628 (2314 infected, mean age: 44.2 years, 62.7% females; 1314 non-infected, mean age: 45.0 years, 63.2% females) participated in the follow-up survey. PCC prevalence at 3, 6, 12, and 18 months was 14.3%, 12.0%, 6.3%, and 5.4%, respectively. Older age, being overweight, comorbidities, severe disease in the acute phase, and low household income were associated with persistent PCC at ≥ 18 months. Compared with no vaccination, ≥ 2 doses of the COVID-19 vaccine prior to infection were associated with a lower PCC risk. These findings highlight PCC as an important public health concern in the post-COVID-19 era. Trial Registration: UMIN000049807.},
}
@article {pmid42152966,
year = {2026},
author = {Farooqui, I and Kumar, M},
title = {Prevalence and Severity of Depression, Anxiety, and Stress Among COVID-19 Survivors in Urban Hazaribagh, Jharkhand: A Community-Based Cross-Sectional Study.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e109015},
pmid = {42152966},
issn = {2168-8184},
abstract = {BACKGROUND: Mental health sequelae following COVID-19 recovery are well-documented in large urban centers, yet community-based data from semi-urban India, particularly Jharkhand, remain scarce.<br><br>OBJECTIVE: To assess the prevalence and severity of depression, anxiety, and stress among COVID-19 survivors in urban Hazaribagh using the Depression Anxiety Stress Scale-21 (DASS-21) and to identify associated sociodemographic and clinical factors.<br><br>MATERIALS AND METHODS: A community-based cross-sectional study was conducted from March 2022 to June 2022, following approval from the Institutional Ethics Committee (IEC), RIMS, Ranchi, obtained prior to data collection. Using systematic random sampling from Integrated Disease Surveillance Programme (IDSP) COVID-19 registers, every seventh from 1,065 first-wave cases and every 17th from 7,686 second-wave cases, 601 consenting recovered adults were enrolled from 640 contacted (response rate: 93.9%). The DASS-21 was administered in its validated Hindi version alongside a semi-structured questionnaire. Data were analyzed in JASP using chi-square and Fisher's exact tests; a value of p<0.05 was considered significant.<br><br>RESULTS: Depression was the most prevalent domain: 337 (56.07%) scored above normal, with 154 (25.62%) moderate, 80 (13.31%) severe, and 44 (7.32%) extremely severe. Anxiety was present at any grade in 260 (43.26%), predominantly mild (211 [35.11%]); stress was elevated in 200 (33.28%). The wave of infection was significantly associated with all three domains (all p&#x2264;0.030). Hospitalization was strongly associated with anxiety and stress (both p<0.001). Age was significantly associated with anxiety (p<0.001) and stress (p=0.015); occupation with depression (p=0.045); and smoking with stress (p=0.014). Gender was not significantly associated with any domain.<br><br>CONCLUSION: COVID-19 survivors in urban Hazaribagh carry a substantial post-recovery psychological burden. Depression at moderate-to-extremely-severe intensity is the most predominant manifestation. Integrating routine DASS-21 screening into community-level post-COVID follow-up care, with priority for high-risk groups, is recommended.},
}
@article {pmid42141891,
year = {2026},
author = {Schmetz, A and Knaul, J and Müller, S and Wilke, T and Yang, J and Spinner, C and Lehmann, C},
title = {Clinical and economic benefits of seasonal COVID-19 vaccination in Germany: results from the ROUTINE-COV19 Study, September 2022 to March 2024.},
journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin},
volume = {31},
number = {15},
pages = {},
pmid = {42141891},
issn = {1560-7917},
mesh = {Humans ; Germany/epidemiology ; *COVID-19/prevention &amp; control/epidemiology/economics ; Male ; Female ; Middle Aged ; SARS-CoV-2/immunology ; Retrospective Studies ; Adult ; *COVID-19 Vaccines/economics/administration &amp; dosage ; *Health Care Costs/statistics &amp; numerical data ; Seasons ; *Vaccination/economics/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data/economics ; Aged ; Sick Leave/economics/statistics &amp; numerical data ; Young Adult ; Adolescent ; },
abstract = {BACKGROUNDVaccinations against COVID-19 were integrated into routine care in Germany in April 2023. However, evidence of the impact of seasonal vaccination remains limited.AIMTo assess the clinical and economic impact of COVID-19 vaccination in routine care during the early SARS-CoV-2-endemic phase in Germany.METHODSA retrospective cohort study using statutory health insurance data from two German federal states (Saxony and Thuringia), covering over 3 million individuals, was conducted. Adults aged ≥ 18 years vaccinated against COVID-19 between 1 September and 30 November 2023 were matched 1:1 with unvaccinated individuals using propensity scores. Outcomes during the 4-month follow-up included occurrence of SARS-CoV-2 infection, long COVID, other respiratory infections, hospitalisations, mortality, healthcare costs and indirect costs caused by sick leave. Rate and hazard ratios (RR, HR) with 95% confidence intervals (CI) were calculated. Sensitivity analyses tested robustness.RESULTSA total of 146,132 individuals (73,066 per group) were matched. COVID-19 vaccination was associated with reduced rates of long COVID (RR: 0.43; 95% CI: 0.26-0.70), respiratory infections (RR: 0.91; 95% CI: 0.87-0.95) and COVID-19-related hospitalisations (RR: 0.41; 95% CI: 0.31-0.54). All-cause mortality was 25% lower among COVID-19-vaccinated individuals (HR: 0.76; 95% CI: 0.70-0.82). Healthcare costs were lower in the vaccinated cohort, particularly for inpatient care, e.g. EUR 1 million savings in COVID-19-related hospitalisations. Indirect costs caused by sick leave were also reduced by EUR 1.3 million.CONCLUSIONSeasonal COVID-19 vaccinations in routine care settings were associated with substantial clinical and economic benefits. These real-world findings support continued implementation of national immunisation recommendations during the endemic phase of SARS-CoV-2 circulation.},
}
@article {pmid42142447,
year = {2026},
author = {Chen, W and Ye, K and Chen, Z},
title = {Comment on "Association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers".},
journal = {Journal of the neurological sciences},
volume = {487},
number = {},
pages = {126002},
doi = {10.1016/j.jns.2026.126002},
pmid = {42142447},
issn = {1878-5883},
}
@article {pmid42144858,
year = {2026},
author = {St-Jean, D and Haynes, S and Ficara, V and Streib, A and Ouédraogo, F and Spiridigliozzi, AM and Minichiello, R and Ehrmann Feldman, D and Mazer, B},
title = {Experiences of People With Long COVID Accessing Rehabilitation Services: A Qualitative Study.},
journal = {Occupational therapy international},
volume = {2026},
number = {1},
pages = {e4676712},
pmid = {42144858},
issn = {1557-0703},
support = {//Foundation Cit&#xe9; de la Sant&#xe9;/ ; //Jewish Rehabilitation Hospital Foundation/ ; },
mesh = {Humans ; Male ; *COVID-19/rehabilitation/psychology ; Female ; Qualitative Research ; *Health Services Accessibility ; Middle Aged ; Adult ; Aged ; SARS-CoV-2 ; *Occupational Therapy ; Social Support ; Interviews as Topic ; },
abstract = {PURPOSE: Long COVID is associated with a range of physical, cognitive, and/or psychological symptoms that significantly affect daily functioning. These individuals require rehabilitation services to address their limitations. This study explored the experiences of people with long COVID regarding access to and receipt of rehabilitation services.<br><br>METHODS: This qualitative study recruited 12 individuals with long COVID from a population-based survey among the population of Laval (Quebec). Semistructured telephone interviews were conducted, recorded, transcribed verbatim, and analyzed using inductive thematic content analysis. Relevant elements were extracted, coded, and organized into themes/subthemes.<br><br>RESULTS: Twelve participants (seven females; five males) participated in the study. We identified three main themes, each with subthemes: (1) impact of long COVID on personal and professional life (e.g., professional life, leisure activities, and social life); (2) rehabilitation services (access barriers, perceptions of services received); and (3) psychosocial support (lack or presence of support). Access to rehabilitation services was hampered by several barriers: difficulties obtaining referrals, financial constraints, lack of awareness among health professionals, and service shortages. Participants who accessed rehabilitation services reported satisfaction with care they received and appreciated the multidisciplinary approach.<br><br>CONCLUSIONS: Improving access to rehabilitation services for people with long COVID is essential to support their recovery, as timely and coordinated rehabilitation can facilitate reintegration into daily activities and reduce functional limitations. Strategies to enhance access include increasing health professional awareness, reducing financial and logistical barriers, and expanding service availability.},
}
@article {pmid42148138,
year = {2026},
author = {Dai, R and Hua, Q and Liu, X and Ma, L and Bao, R and Lei, H and Yu, P and Liao, Y and Yang, J and Han, S and Jiang, J and Zhang, H},
title = {Safety, immunogenicity, and long COVID outcomes following inactivated COVID-19 vaccine boosters in elderly Chinese: a prospective cohort study.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1813716},
pmid = {42148138},
issn = {1664-3224},
mesh = {Humans ; Aged ; Male ; Female ; *COVID-19/prevention &amp; control/immunology/epidemiology ; *COVID-19 Vaccines/immunology/adverse effects/administration &amp; dosage ; Middle Aged ; Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Antibodies, Neutralizing/blood/immunology ; Aged, 80 and over ; Prospective Studies ; China/epidemiology ; Vaccines, Inactivated/immunology/adverse effects/administration &amp; dosage ; *Immunogenicity, Vaccine ; *Immunization, Secondary ; Immunoglobulin G/blood/immunology ; East Asian People ; },
abstract = {BACKGROUND: Adults aged ≥60 years face elevated risks of severe COVID-19 and long COVID. Although inactivated SARS-CoV-2 vaccines are safe and effective, critical gaps remain regarding optimal booster timing, durability of immune responses, and protection against emerging variants in this vulnerable population.<br><br>METHODS: In this prospective cohort study in Zhejiang Province, China, 450 adults aged &#x2265;60 years were randomized to receive an inactivated SARS-Cov-2 vaccine (CoronaVac or Covilo) under three dosing schedules. Neutralizing antibody titers, SARS-CoV-2-specific IgG, and variant-specific neutralization were evaluated using serum samples collected at multiple timepoints. Safety outcomes included local and systemic adverse reactions and long COVID symptoms.<br><br>RESULTS: Participants (age: 60-80 years; 50.9% male) with balanced baseline demographics were stratified into six subgroups by vaccine type and schedule (S1/S2/S3; n=75 each; all P>0.05). Adverse reaction incidence was low (0.0%-8.0%), with CoronaVac-S3 recipients experiencing significantly more local reactions than Covilo-S3 recipients (8.0% vs. 0.0%; P&#xa0;=&#xa0;0.0124). Immunogenicity varied markedly at 1 month post vaccination, with the highest geometric mean titers (GMTs) of neutralizing antibodies in both S3 groups (Covilo: 57.2; CoronaVac: 59.4; P<0.001 vs. respective S1/S2 groups), and CoronaVac-S1 inducing higher GMTs than Covilo-S1 (21.8 vs. 15.4; P&#xa0;=&#xa0;0.009). At 12 months post vaccination, GMTs remained highest in Covilo-S3 (9.9), while CoronaVac-S2 exceeded Covilo-S2 (8.0 vs. 5.1; P&#xa0;=&#xa0;0.021). Covilo-S2 and -S3 were superior to their CoronaVac counterparts in inhibition against the wild-type strain and Delta variant at 1 month post vaccination (all P<0.05). Multivariate analysis identified male sex as a protective factor against COVID-19 symptoms, long COVID, and fatigue (odds ratios <0.5 and P<0.05 for all).<br><br>CONCLUSIONS: A third booster of inactivated SARS-CoV-2 vaccine administered within 2-6 months of the second dose is safe and significantly boosts humoral immunity in adults &#x2265;60 years. The three-dose Covilo regimen and a 6-month dosing interval optimized immunogenicity and were associated with the lowest risks of COVID-19 symptoms and long COVID, highlighting the importance of vaccine-specific and interval-adjusted booster strategies for older populations.},
}
@article {pmid42148664,
year = {2026},
author = {Arnaboldi, PM and Becker, J and Nath, A and Coyle, PK and Handel, A and Sellati, TJ and Gomes-Solecki, M and Garcet, S and Henderson, MK and Mullins, P and Cowan, E and McCombie, WR and Wellins, AM and Allegretta, M and Bergquist, J and Schutzer, SE},
title = {Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag016},
pmid = {42148664},
issn = {1460-2156},
support = {//Banbury Center of Cold Spring Harbor Laboratory/ ; },
abstract = {Infection-associated chronic illnesses (IACIs) encompass a spectrum of poorly understood syndromes often marked by significant neurologic and multisystem symptoms following an infectious event. This review focuses on several diseases representative of the IACI spectrum. These are post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). Their clinical and biological complexity, combined with a lack of clear diagnostic criteria and objective available laboratory biomarkers, makes them difficult to distinguish from conditions with overlapping features. This presents challenges for research studies, as well as diagnosis and clinical management. This diagnostic ambiguity, coupled with heterogeneous patient presentations, has led to challenges in research, including misclassification of study participants and inconsistent or irreproducible findings. Some PTLDS research exemplifies these issues, which also extend to other IACIs. To advance the field, we highlight key methodological refinements and approaches for studying IACIs, including rigorous participant selection, standardized sample collection protocols, and the use of appropriate control groups, including those with microbiologic proof of the initial infection when known and technologically feasible. We also address broader influences on research quality, such as stigma, historical neglect, and the urgency to find treatments, which have contributed to the proliferation of poorly controlled studies and questionable practices. Drawing lessons from past challenges, we propose a path forward grounded in fit-for-purpose methodological rigour to improve scientific understanding and support evidence-based therapeutic development for IACIs.},
}
@article {pmid42149360,
year = {2026},
author = {Mertens, A and Smith, J and Bergs, I and Fischer, J and Jansen, S and Breitschwerdt, S and Pracht, E and Killer, A and Schipper, L and Kuklik, N and Frank, M and Schwichtenberg, J and Bührmann, S and Zeissler, L and Dreher, M and Rockstroh, J and Rohn, H and Lehmann, C and Tepasse, PR and Schmidt, B and Dragano, N and Bode, J and Luedde, T and Jensen, BE and , },
title = {Characterization of post-COVID syndrome by self-perceived symptom severity stratified by infection wave: beyond COVID, a prospective, multicenter cohort study in Germany.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {42149360},
issn = {1439-0973},
abstract = {BACKGROUND: Post-COVID syndrome (PCS) refers to persistent or new-onset symptoms 3 months after SARS-CoV-2 infection lasting for at least 2 months. The characterization of PCS varies across studies, with a substantial heterogeneity regarding different study samples, survey instruments, and follow-up periods. This is particularly the case in hospitalized patients vs. outpatients, as well as regarding different variants of concern (VOCs) and their impact on the frequency and severity of specific symptoms.<br><br>METHODS: The study population of Beyond COVID was recruited in six German cities by inviting (1) individuals registered as SARS-CoV-2 PCR positive at the local Public Health Authorities and (2) previously hospitalized patients with infection date after 1st March 2021. Participants were allocated to the predominant VOC of their first infection. Questionnaires to assess pre-existing conditions, symptoms during infection, and persisting symptomswere performed. Follow-up at sixth-month intervals is planned for 3&#xa0;years. The study is ongoing. This publication describes the parameters at the baseline visit (BV).<br><br>RESULTS: We included 1257 participants (13% hospitalized-based; 87% population-based). Most participants had BA.2 (n&#x2009;=&#x2009;436; 35%), followed by Delta (n&#x2009;=&#x2009;336; 27%), BA.1 (n&#x2009;=&#x2009;238; 19%), and Alpha (n&#x2009;=&#x2009;218; 17%). The mean age was 47.1&#xa0;years, and 59% of the participants were female. 72% reported at least one persisting symptom. Fatigue was the most frequent ongoing symptom (33%), followed by concentration disorders (25%) and dyspnoea (22%). Female sex, lower education, and a shorter period between infection and BV were associated with higher rates of persisting symptoms and symptom severity. Among all VOCs, participants with BA.1 and BA.2 had the lowest rates of persisting symptoms and symptom severity.<br><br>CONCLUSION: Analysis of baseline data from the Beyond-COVID cohort confirms a high percentage of persistent symptoms. Omicron variants had lower rates of persistent symptoms and symptom severity. We are confident, that long-term follow-up and the additional results from our clinical examinations, blood samples, sociodemographic and psychosocial data will further contribute to the characterization of PCS.},
}
@article {pmid42141452,
year = {2026},
author = {Gao, Y and Zhu, Q and Xu, M},
title = {Chronic fatigue syndrome in nursing practice: a concept analysis.},
journal = {BMC nursing},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12912-026-04749-y},
pmid = {42141452},
issn = {1472-6955},
abstract = {BACKGROUND: Nurses are essential in chronic fatigue syndrome (CFS) management, serving as care coordinators and patient advocates, but currently lack a unified guiding framework. CFS affects about 0.89% of the global population based on CDC-1994 criteria, with higher prevalence in women. Since its initial definition in 1988, over 25 diagnostic criteria have been introduced, leading to ongoing confusion about core symptoms and diagnosis. This inconsistency poses significant challenges for nurses, including difficulties in patient identification, inconsistent assessment approaches, and lack of standardized care pathways. A clear theoretical model is needed to improve nursing assessments, intervention planning, and care standardization.<br><br>METHODS: A concept analysis was conducted using the Walker and Avant's eight-step method. Eight databases were systematically searched for literature from January 1988 to December 2025. Studies on CFS definitions, diagnostic criteria, or conceptual frameworks were included if they addressed key attributes, antecedents, consequences, or measurement methods. Two graduate students and professors independently performed two-stage screening and data extraction. Multiple discussion rounds ensured analytical rigor.<br><br>RESULTS: Sixty-eight studies were included. CFS antecedents included infections, immune dysregulation, genetics, and stress. Five core attributes were identified as defining features of CFS in the reviewed literature: persistent severe fatigue, post-exertional malaise (PEM), non-restorative sleep, cognitive impairment and/or orthostatic intolerance, and multisystem involvement. Consequences involved disability, poor quality of life, psychological distress, social isolation, and economic burden. Empirical referents included diagnostic criteria, symptom scales, and functional measures.<br><br>CONCLUSIONS: This study proposed a nursing-oriented conceptual framework for CFS based on the reviewed literature, identifying five core features that may help distinguish it from general fatigue. The framework suggests plausible directions for nursing practice, including prioritizing PEM assessments, promoting energy management and pacing as potential interventions, and considering nurses as care coordinators in multidisciplinary teams. It may also contribute to CFS-focused nursing education and the development of assessment instruments. Given shared pathophysiological features reported in the literature, the framework may offer a conceptual basis for application to post-infectious fatigue conditions such as long COVID, though this transferability requires empirical validation in specific populations and clinical contexts.},
}
@article {pmid42141069,
year = {2026},
author = {Ali, YH and Abbas, U and Khalid, MU and Ahmed, I and Hussain, N and Baloch, I and Mahboob, H and Zafar, AA and Musawwir, UA},
title = {Integrated immune, apoptotic and mitochondrial gene dysregulation in Long COVID and their association with symptom burden at 10 months post-infection.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-53455-x},
pmid = {42141069},
issn = {2045-2322},
abstract = {Long COVID is characterized by persistent symptoms following acute SARS-CoV-2 infection, yet its biological mechanisms remain incompletely understood. Emerging evidence suggests that immune dysregulation, mitochondrial dysfunction, and altered cell survival pathways may contribute to prolonged symptomatology. In this cross-sectional study, peripheral blood mononuclear cells were collected from individuals with Long COVID approximately 10 months post-infection and from recovered individuals without Long COVID symptoms. Symptom burden was assessed using a composite domain-based score. mRNA expression of immune and antiviral genes (IL-6, IL-1β, IL-10, SOCS3, HIF-1α, OAS1, MAVS, IFN-α, IFN-γ), anti-apoptotic markers (MCL1, BCL-2, XIAP, LIVIN), cell cycle kinases (CDK4, CDK6), mitochondrial biogenesis and dynamics markers (NRF1, TFAM, PGC-1α, DRP1, MFN1/2, OPA1), and mitophagy regulators (PARKIN, PINK1) were quantified using quantitative real-time PCR. Data was analyzed by SPSS and GraphPad Prism. Individuals with Long COVID demonstrated significantly higher expressions of IL-6, IL-1β, IL-10, SOCS3, HIF-1α, OAS1, MAVS, NRF1, DRP1, PARKIN, MCL1, and LIVIN compared with recovered controls after using the Benjamini-Hochberg False Discovery Rate (FDR) method. Several transcriptional markers, particularly HIF-1α, IL-1β, IL-10, and NRF1, remained independently associated with symptom burden after adjustment for age and sex. Correlation analysis demonstrated coordinated transcriptional co-expression patterns across immune, antiviral, mitochondrial, and apoptosis-related genes. Long COVID at 10 months post-infection is associated with coordinated transcriptional alterations across multiple biological pathways. The association of these changes with symptom burden suggests a potential link between persistent immunometabolic activation and clinical manifestations. These findings are exploratory and highlight the need for longitudinal and functional studies to further elucidate underlying mechanisms.},
}
@article {pmid42134898,
year = {2026},
author = {eBioMedicine, },
title = {Towards biology-informed therapies for long COVID.},
journal = {EBioMedicine},
volume = {127},
number = {},
pages = {106302},
doi = {10.1016/j.ebiom.2026.106302},
pmid = {42134898},
issn = {2352-3964},
}
@article {pmid42135534,
year = {2026},
author = {Rosa, GD and Raffo, M and Tammaro, S and Morelli, M and Arcaniolo, D and Pandolfo, SD and Sciorio, C and Romano, L and Manfredi, C and Cindolo, L and De Sio, M and Spirito, L},
title = {The impact of COVID-19 on sexual behavior, male sexual function, and reproductive health: an interdisciplinary narrative review from a urological perspective.},
journal = {International urology and nephrology},
volume = {},
number = {},
pages = {},
pmid = {42135534},
issn = {1573-2584},
abstract = {The COVID-19 pandemic profoundly modified daily life and interpersonal relationships, with relevant consequences on sexual health, which integrates biological, psychological, and social components. This narrative review summarizes current evidence regarding the impact of the pandemic on sexual behavior, sexual function, and male reproductive health. A comprehensive literature search of recent studies and clinical reports was performed focusing on psychosexual wellbeing, erectile function, fertility, and healthcare access during and after infection or lockdown periods. Current evidence indicates that lockdown-related stress, anxiety, and depression were consistently associated with reduced sexual desire and frequency of sexual activity, as reported in predominantly cross-sectional, questionnaire-based studies conducted during lockdown periods, particularly among couples with children and non-cohabiting partners, whereas alternative sexual practices increased. Sexual activity generally recovered after restrictions were lifted. Emerging data suggest a possible association between COVID-19 and erectile dysfunction mediated by endothelial damage, hypogonadism, and psychological distress, while long-COVID symptoms may further worsen sexual function. Male fertility alterations related to inflammatory and oxidative stress pathways have also been reported. Overall, the pandemic primarily affected sexuality through psychosocial mechanisms, although potential organic effects of SARS-CoV-2 infection on erectile function and fertility cannot be excluded. This review provides an interdisciplinary synthesis of current evidence with a specific focus on clinically relevant urological implications, including erectile dysfunction and male reproductive health, which remain incompletely addressed in the existing literature.},
}
@article {pmid42136400,
year = {2026},
author = {Jin, X and Wei, F and Kandala, SS and Lopez, G and Laubichler, MD and Bils, T and Li, R and Gorantla, R},
title = {The impact of culturally tailored video interventions for Long COVID among Hispanic/Latino populations.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04162},
doi = {10.7189/jogh.16.04162},
pmid = {42136400},
issn = {2047-2986},
mesh = {Humans ; Female ; *Hispanic or Latino ; Male ; *COVID-19/ethnology/prevention &amp; control ; Adult ; Middle Aged ; *Health Education/methods ; Arizona/epidemiology ; *Health Knowledge, Attitudes, Practice/ethnology ; Young Adult ; SARS-CoV-2 ; *Video Recording ; Adolescent ; White ; },
abstract = {BACKGROUND: Long COVID has disproportionately affected Hispanic/Latino communities, particularly in Arizona. Structural inequities contribute to disparities, but limited culturally tailored health information remains an underexplored barrier to effective communication. This study evaluated the impact of culturally designed Long COVID educational videos for Hispanic/Latino audiences.<br><br>METHODS: We developed animated videos incorporating cultural symbols and diversity cues. Participants completed pre- and post-intervention surveys assessing Long COVID knowledge. Pre-post regression analyses examined knowledge gains, subgroup differences (education, gender, lived experience), and the influence of cultural design elements.<br><br>RESULTS: Baseline knowledge was higher among participants with greater educational attainment; however, post-intervention knowledge levels were similar across education groups. Female participants demonstrated lower scores than males, diverging from typical health information-seeking trends. Participants with lived experience of Long COVID reported higher baseline knowledge. Cultural design features, including symbolism and perceived diversity, showed modest effects, particularly among younger viewers. Overall, knowledge increased significantly following video exposure across all subgroups.<br><br>CONCLUSIONS: Culturally tailored Long COVID videos effectively enhanced knowledge among Hispanic/Latino audiences, mitigating educational disparities and engaging individuals with diverse experiences. While cultural design elements had limited influence, they may enhance relevance for specific subgroups. These findings support the potential of culturally responsive video interventions to improve health education access in underserved communities and highlight areas for refinement in future multimedia health communication strategies.},
}
@article {pmid42136829,
year = {2026},
author = {Luo, T and Luo, Y and Liu, D and Jin, H and An, Y and Huang, J and Luo, K and Guo, Y and Wang, D and Huang, L and Wu, X},
title = {Acupuncture for cognitive functions in post-COVID-19 condition: study protocol of a three-armed, randomized controlled trial with multimodal MRI.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1796351},
pmid = {42136829},
issn = {2296-858X},
abstract = {BACKGROUND: Post-COVID-19 condition (PCC), commonly called long COVID, is a prevalent sequela of SARS-CoV-2 infection and can affect multiple organ systems. Cognitive dysfunction is one of the most common symptoms in PCC, with a prevalence of 22%. It can persist for years and significantly reduce patients' quality of life. The brain network is the neural basis underlying human cognitive processes. Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) studies have revealed that cognitive impairments across attention, memory, executive function, and language are associated with alterations in network characteristics for PCC. Currently, there is no accepted therapy for cognitive impairment in PCC. Acupuncture has the potential to improve cognitive deficits in PCC. This trial aims to investigate the effect of acupuncture on cognitive functions in patients with PCC, and to explore the underlying mechanism of its effects on cognition in this condition using DTI and fMRI.<br><br>METHODS: In this three-armed, randomized controlled trial, 117 PCC patients with cognitive symptoms will be randomly assigned in a 1:1:1 ratio to verum acupuncture (VA), sham acupuncture (SA), or a waitlist control group. Participants in the VA and SA groups will receive three sessions of treatment per week for 8&#x202f;weeks. The primary outcome measures are the changes in Addenbrooke's Cognitive Examination-III (ACE-III) total score and phonemic fluency test score at week 8. The secondary outcome measures include the Digit Span Test (DST), Symbol Digit Modality Test (SDMT), Trail Making Test (TMT), Rey's Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test (RCFT), Stroop Color Word Test (SCWT), category fluency test, action fluency test, and Boston Naming Test (BNT-30), as well as global and regional topological measures of structural and functional brain networks constructed from DTI and fMRI data. Additionally, the Fatigue Severity Scale (FSS), the Generalized Anxiety Disorder-7 (GAD-7), the 24-item Hamilton Depression Scale (HAMD-24), and the MOS 36-item Short Form Health Survey (SF-36) will also be measured.<br><br>DISCUSSION: The results of this study will reveal the effect of acupuncture treatment on cognitive functions for PCC and provide insights into the mechanisms by which acupuncture may improve cognition in PCC.<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (www.clinicaltrials.gov), identifier: NCT07355751.},
}
@article {pmid42137753,
year = {2026},
author = {Liu, A and Hodkiewicz, VA and Benson, M and Patel, M and Roach, P},
title = {Patient with Acute-On-Chronic Cholecystitis Complicated by Portal Vein Thrombosis Following "Long COVID-19": A Case Report.},
journal = {The International journal of angiology : official publication of the International College of Angiology, Inc},
volume = {35},
number = {2},
pages = {156-160},
pmid = {42137753},
issn = {1061-1711},
abstract = {Portal vein thrombosis (PVT) is a rare but serious complication of hypercoagulable states or conditions that increase portal pressure, such as liver cirrhosis, inherited or acquired coagulation cascade abnormalities, myeloproliferative disorders, malignancy, inflammation, or infection. COVID-19 has been associated with a prothrombotic state, leading to both arterial and venous thromboses. Here, we present a patient with minimal hypercoagulable risk factors who presented with PVT and acute-on-chronic cholecystitis with bacteremia, likely provoked by residual hypercoagulability from a "long COVID-19" syndrome. An 81-year-old male developed PVT as a complication of acute-on-chronic cholecystitis, with contributing factors potentially including hypercoagulability related to prior COVID-19 infection more than 4 months prior. PVT should remain a diagnostic consideration in patients with various hypercoagulable risk factors, including long COVID-19, who present with relevant clinical findings. There should be a low threshold for the pursuit of further diagnostic imaging, given the serious consequences of delayed diagnosis.},
}
@article {pmid42138268,
year = {2026},
author = {Camps-Massa, P and Pérez-Mormeneu, J and Guevara-Nuñez, D and Saiz-Escobedo, L and Calatayud, L and González-Díaz, A and Sanllorente, A and Vicens-Zygmunt, V and Santos, S and Morros, R and Salvador-González, B and Domínguez, M&#xc1; and Martí, S and , },
title = {Gut microbiome shift in long COVID: impact of disease and montelukast treatment.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04164},
doi = {10.7189/jogh.16.04164},
pmid = {42138268},
issn = {2047-2986},
mesh = {Humans ; *Cyclopropanes/therapeutic use ; *Sulfides/therapeutic use ; *Quinolines/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Acetates/therapeutic use ; *COVID-19/microbiology/complications ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; SARS-CoV-2 ; Feces/microbiology ; Adult ; Aged ; Longitudinal Studies ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Long COVID-19 is a post-infectious syndrome with persistent symptoms that can involve multiple organ systems. Evidence suggests that SARS-CoV-2 infection may disrupt gut microbiome composition, potentially contributing to long-term effects. As treatment remains symptom-based, interest has grown in repurposing drugs like montelukast. However, non-antibiotic medications may also alter gut microbial communities, raising questions about their impact. Here, we compare gut microbiota between long COVID patients and healthy controls and examine how montelukast treatment affects microbial composition.<br><br>METHODS: We analysed stool samples from long COVID patients and healthy controls using 16S rRNA gene sequencing (Illumina MiSeq). We evaluate alpha (Shannon) and beta (Bray-Curtis) diversity, followed by relative abundance and linear discriminant effect size analysis, to identify differentially abundant taxa. This proof-of-concept study included a cross-sectional comparison and a longitudinal analysis of montelukast-treated patients vs. placebo.<br><br>RESULTS: Cross-sectional analysis revealed a significant structural reorganisation of the gut microbial community in long COVID patients, although overall species richness was largely maintained. Linear discriminant effect size analysis revealed that this architectural shift was driven by an enrichment of Firmicutes (Agathobacter and Faecalibacterium genera) in the long COVID group, while healthy controls were characterised by higher abundances of the phyla Verrucomicrobiota and Actinobacteriota, as well as genera Alistipes and Akkermansia. Longitudinal analysis demonstrated that the broader community structure remained stable in both groups; however, montelukast treatment led to a specific enrichment of the genus Dialister, suggesting targeted and potentially transient effects without disrupting the overall microbial landscape.<br><br>CONCLUSIONS: Long COVID is characterised by a significant restructure of the gut ecosystem. This qualitative dysbiosis reflects a shift in homeostatic balance, where the core microbial community remains present, but its proportions are altered. Short-term montelukast treatment shows a minimal impact on the microbial landscape, suggesting treatment does not further destabilise the gut environment. These findings highlight the specific and targeted nature of gastrointestinal involvement in long COVID.},
}
@article {pmid42140088,
year = {2026},
author = {Kohli, M and Maschio, M and Lee, A and Kissler, S and Carroll, S and van de Velde, N and Beck, E and Balogh, O and Joshi, K},
title = {The cost-effectiveness of vaccination against COVID-19 in at-risk populations and older adults in the United Kingdom: Projections using a dynamic transmission model.},
journal = {Vaccine},
volume = {85},
number = {},
pages = {128687},
doi = {10.1016/j.vaccine.2026.128687},
pmid = {42140088},
issn = {1873-2518},
abstract = {OBJECTIVE: This study estimates the potential clinical impact and cost-effectiveness of an Autumn COVID-19 vaccination campaign in the United Kingdom (UK) using a variant-adapted mRNA-1273 vaccine in those aged ≥65 years and those aged 6 months-64 years at high risk (base case population) of severe outcomes, as well as the effect of implementing more restrictive vaccine eligibility requirements.<br><br>METHODS: A Susceptible-Exposed-Infected-Recovered (SEIR) model was used to predict COVID-19 cases and hospitalisations in the UK. A COVID-19 vaccination and infection consequences decision tree was used to predict health outcomes, costs and quality-adjusted life-year (QALY) losses associated with symptomatic SARS-CoV-2 infections as well as costs and QALY losses associated with COVID-19 vaccination and adverse events over a 1-year time horizon.<br><br>RESULTS: Compared to no vaccination, an Autumn mRNA-1273 vaccination campaign is predicted to decrease the number of symptomatic infections from 21.9 million to 20.0 million, and the number of hospitalisations from 150,000 to 116,000. COVID-related deaths and long COVID cases are decreased by 7200 and 18,000, respectively. Costs saved are &#xa3;467.7 million with 52,000 QALYs gained, resulting in an incremental cost-effectiveness ratio (ICER) of &#xa3;8963/QALY gained. The ICER was most sensitive to infection incidence, population immunity before the vaccination campaign, vaccine effectiveness against hospitalisation, and hospitalisation probabilities. Narrowing the vaccination eligibility criteria to those aged &#x2265;75&#xa0;years and those aged 6&#xa0;months-74&#xa0;years at high risk of severe outcomes results in fewer outcomes prevented, with 525,300 more symptomatic infections, 6000 more hospitalisations, 1100 additional deaths, and 5200 additional cases of long COVID, compared to the base case. Vaccination of the broader population compared to the narrower population is associated with an ICER of &#xa3;11,753/QALY gained.<br><br>CONCLUSIONS: Vaccinating adults aged &#x2265;65&#xa0;years and high-risk individuals 6&#xa0;months-64&#xa0;years remains cost-effective compared both to no vaccination and vaccination of the narrower population.},
}
@article {pmid42140539,
year = {2026},
author = {Tamariz, L and Shehadeh, LA and Bast, E and Klimas, N and Palacio, A},
title = {The role of the endothelium in long COVID.},
journal = {Vascular pharmacology},
volume = {},
number = {},
pages = {107654},
doi = {10.1016/j.vph.2026.107654},
pmid = {42140539},
issn = {1879-3649},
abstract = {SARS-CoV2 infection significantly increases the risk of cardiovascular events through multiple interconnected mechanisms including systemic inflammation, dysautonomia, endothelial dysfunction, and prothrombotic states. The endothelium plays a critical role in this increase in risk together with dysautonomia and mast cell activation. SARS-CoV2 activates endothelial cells creating a pro-inflammatory, and pro-thrombotic phenotype. This phenotype could lead to microcirculatory changes that decrease oxygen delivery to tissues because of loss of laminar flow, lack of nitric oxide dependent vasodilation, increased viscosity and abnormal constriction of vascular smooth muscle cells due to neuropathy. There are several ways of identifying patients with endothelial dysfunction and the most used is flow mediated dilation. Many randomized trials have already found significant treatments for endothelial dysfunction and include antihypertensives, statins, beta-blockers, supplements and lifestyle interventions. Only two studies using vitamin C and L-arginine demonstrated improvements in flow mediated dilation in patients with long COVID.},
}
@article {pmid42129014,
year = {2026},
author = {Saurel, M and Fornasieri, I and Del Sordo, GC and Chatain, C and Fantini, ML and Gruet, M and Saidi, O},
title = {Sleep in myalgic encephalomyelitis/chronic fatigue syndrome shows marked night-to-night fluctuation under free-living conditions-results from a matched case-control study.},
journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine},
volume = {22},
number = {1},
pages = {},
pmid = {42129014},
issn = {1550-9397},
mesh = {Humans ; *Fatigue Syndrome, Chronic/complications/physiopathology ; Case-Control Studies ; Male ; Female ; Adult ; Sleep Quality ; Middle Aged ; *Sleep/physiology ; Accelerometry ; *Sleep Wake Disorders ; },
abstract = {PURPOSE: Unrefreshing and non-restorative sleep is a hallmark complaint in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, little is known about their habitual sleep and night-to-night fluctuations under real-life conditions. This study aimed to characterize sleep, and the intraindividual variability (IIV) of sleep in people living with ME/CFS compared with matched controls.<br><br>METHODS: In this case-control study, 38 ME/CFS and 38 controls wore a wrist accelerometer continuously for 7 days and completed concurrent sleep diaries, the Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Within the ME/CFS group, participants were also stratified by symptom severity using the Bell Disability Scale. Sleep IIV was quantified using the coefficient of variation, the root mean square of successive differences, and the Bayesian variability model, respectively.<br><br>RESULTS: Compared with controls, individuals with ME/CFS spent significantly more time in bed and exhibited poorer sleep efficiency (SE) (all p&#x2009;<&#x2009;0.05). Despite a longer time in bed, total sleep time did not differ between groups. ME/CFS participants also displayed significantly greater IIV in SE. By contrast, sleep timing (bedtime) was more regular among ME/CFS. Exploratory analyses did not detect clear differences across ME/CFS severity subgroups for mean sleep variables or variability indices.<br><br>CONCLUSION: Under real-life conditions, people with ME/CFS exhibit poor sleep quality and unstable SE. These findings highlight sleep IIV as a clinically relevant dimension of sleep health in ME/CFS.<br><br>Unrefreshing sleep is a core symptom of ME/CFS, yet most evidence relies on single- or two-night laboratory assessments that may not reflect habitual sleep under real-life conditions. Moreover, night-to-night sleep variability, a potentially critical dimension of sleep health, has not been systematically examined in ME/CFS.<br><br>STUDY IMPACT: Using week-long wrist accelerometry, this study shows that under free-living conditions sleep in ME/CFS is characterized not only by impaired sleep efficiency but also by pronounced night-to-night variability, despite relatively stable bedtime compared to controls. These findings highlight sleep efficiency variability as a clinically relevant feature of ME/CFS and underscore the need for multi-night assessment and targeted strategies addressing sleep variability.},
}
@article {pmid42129072,
year = {2026},
author = {Veenstra, TD},
title = {Viral Prognosis Using Proteomics.},
journal = {Advances in experimental medicine and biology},
volume = {1511},
number = {},
pages = {75-102},
pmid = {42129072},
issn = {0065-2598},
mesh = {Humans ; *COVID-19/virology/diagnosis/metabolism/epidemiology ; *Proteomics/methods ; *SARS-CoV-2/genetics/metabolism/pathogenicity ; Prognosis ; Pandemics ; },
abstract = {So much was learned during the COVID-19 pandemic of 2020-2023. Some of the things that were learned were obvious. Many people in the public learned about social distancing, personal hygiene, and how to conduct a COVID-19 diagnostic test. Pharmaceutical companies and government organizations learned to efficiently work together to produce and distribute vaccines in record time. Although it may have generated controversy, the value in getting vaccinated was revalidated. There were other things that the world learned, although it was not as obvious. The effect of vaccination rate on preventing virus mutation became evident during the pandemic. The original SARS-CoV-2 virus that started the pandemic mutated several times over the course of the pandemic. One thing that became clear during the pandemic was the lack of knowledge on how SARS-CoV-2 infection would affect individuals during the course of the disease. This inability to accurately prognose the disease made it difficult to personalize treatments for specific individuals and the distribution of resources to protect the most vulnerable populations challenging. What is required to increase the accuracy of prognosis is more knowledge about how dynamic changes occur within the host cell during viral infection. Since many proteins become dysregulated during infection, proteomics is a prime technology for gaining this knowledge to increase prognostic capabilities and enable personalized treatments that alleviate the suffering viruses cause on humanity.},
}
@article {pmid42130374,
year = {2026},
author = {Kell, DB and Pretorius, E},
title = {Assessing the Health and Functionality of the Microcirculation Using Thermal Imaging.},
journal = {Journal of biophotonics},
volume = {19},
number = {5},
pages = {e70270},
doi = {10.1002/jbio.70270},
pmid = {42130374},
issn = {1864-0648},
support = {18//Balvi/ ; //Polybio/ ; //Kanro/ ; },
mesh = {*Microcirculation ; Humans ; *Thermography/methods ; Animals ; },
abstract = {The microcirculation, composed of vessels below 100 μm in diameter, sustains tissue perfusion and metabolic exchange. Its dysfunction is increasingly implicated in chronic, inflammatory, and thrombotic disorders such as diabetes, sepsis, cardiovascular disease, and Long COVID. Accurate, noninvasive assessment of microvascular health is therefore clinically significant. Infrared thermal imaging provides a rapid, contact-free, and physiologically coherent means of visualizing temperature distributions that reflect underlying blood flow. Because thermal gradients directly correspond to perfusion heterogeneity, this approach offers an interpretable surrogate for assessing microvascular function. Here, we review the physical principles of thermal imaging, summarize its application to the peripheral circulation, and compare it with established modalities including nailfold capillaroscopy and laser-based techniques. We also outline its utility across diverse pathologies associated with fibrinaloid microclot complexes and endothelial injury. Thermal imaging thus emerges as an inexpensive/scalable tool for evaluating microcirculatory dysfunction in both research and (where approved) in clinical settings.},
}
@article {pmid42130887,
year = {2026},
author = {Taylor, I and Boyd, JK and McIndoo, E and Ammons, MCB},
title = {A retrospective cohort study of viral and sociodemographic determinants of long COVID among Idaho veterans.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1625363},
pmid = {42130887},
issn = {2296-2565},
mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/virology ; *Veterans/statistics &amp; numerical data ; Middle Aged ; Retrospective Studies ; SARS-CoV-2/isolation &amp; purification ; Aged ; Idaho/epidemiology ; Adult ; Rural Population/statistics &amp; numerical data ; },
abstract = {PURPOSE: To investigate associations between cardiopulmonary, neuropsychiatric, and multisystem long COVID phenotypes, and sequence-defined SARS-CoV-2 viral variant and sociodemographic predictors in a population from a rural state.<br><br>METHODS: SARS-CoV-2 clinical samples were collected from 1,120 veterans treated at the Veterans Affairs (VA) Medical Center in Boise, Idaho from April 2, 2020 to December 20, 2022. Viral variants were identified through sequencing and annotated with clinical data from the VA Corporate Data Warehouse, as well as CDC rurality and social vulnerability. Cardiopulmonary, neuropsychiatric, and multisystem long COVID phenotypes were determined by the addition of one or more ICD-10 codes 90-270&#x202f;days post-infection. Multinomial logistic regression was used to estimate phenotype prevalence in a base model with predictors viral variant, age, sex, rurality, and social vulnerability, as well as in models that adjusted for patient health (comorbidity, healthcare utilization, and smoking status), and treatments (vaccination and Paxlovid).<br><br>FINDINGS: Female patients experienced more neuropsychiatric long COVID and less recovery, whereas the neuropsychiatric phenotype was less prevalent among older patients. Omicron variants had less recovery and more multisystem long COVID relative to pre-Delta-a finding that may indicate an association between infection with Omicron and post-acute gastrointestinal symptoms.<br><br>CONCLUSION: This study is perhaps the largest to investigate viral variant effects on long COVID using sequence rather than date-based variant definitions, and is also unique in its focus on a population living in one of the most rural states in the United States. Our results are consistent with other studies finding contributions from both biological and social predictors to long COVID outcomes.},
}
@article {pmid42131622,
year = {2026},
author = {Ikeda, G and Koike-Ieki, M and Inoue, H and Dadhania, AV and El Kamari, V and Jagannathan, P and Geng, LN and Miglis, MG and Shafer, RW and Yang, PC and Bonilla, HF},
title = {Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {Open forum infectious diseases},
volume = {13},
number = {5},
pages = {ofag209},
pmid = {42131622},
issn = {2328-8957},
abstract = {BACKGROUND: Long COVID (LC) is characterized by symptoms persisting at least 3 months after SARS-CoV-2 infection and affecting multiple organ systems. Diagnosis relies on subjective criteria without established biomarkers. Immune dysregulation and mitochondrial dysfunction are implicated in LC pathophysiology. Given clinical overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we investigated whether plasma extracellular vesicles (EVs) capture shared molecular signatures.<br><br>METHODS: Plasma EVs from 125 individuals across pandemic-era and prepandemic cohorts were analyzed. The pandemic-era cohort included COVID-Recovered, LC with ME/CFS phenotype (LC-ME/CFS), and ME/CFS without infection (pan-ME/CFS). The prepandemic cohort included ME/CFS and matched controls. Extracellular vesicles were isolated using size-exclusion chromatography. Concentration and size were assessed by nanoparticle tracking analysis, and surface markers and mitochondrial membrane potential were evaluated by flow cytometry.<br><br>RESULTS: Both pan-ME/CFS and LC-ME/CFS exhibited elevated EV concentrations compared with COVID-recovered controls after false discovery rate (FDR) correction (q = 0.0042 and 0.0024). Leukocyte-, monocyte/macrophage-, and platelet-derived EVs were increased, whereas B cell-derived EVs were reduced in both groups. Compared with controls, pan-ME/CFS demonstrated increased mitochondrial membrane potential in B cell-, monocyte/macrophage-, and NK cell-derived subsets after FDR correction, whereas no significant differences were observed in LC-ME/CFS. Prepandemic ME/CFS showed a nominal increase in leukocyte-derived EVs that did not persist after correction, whereas elevated mitochondrial membrane potential in B cell-derived EV subsets remained significant.<br><br>CONCLUSIONS: ME/CFS and LC-ME/CFS demonstrate partially overlapping immune cell-associated EV alterations. Mitochondrial membrane potential alterations within selected immune-derived EV subsets, particularly B cell-associated EVs, suggest immune-metabolic involvement. Plasma EV profiling may inform future biomarker development.},
}
@article {pmid42133310,
year = {2026},
author = {Thiel, F and Soares, RN and Peter, RS and Göpel, S and Nieters, A and Rothenbacher, D and Kern, WV and Nieß, AM and Mattioni Maturana, F},
title = {Impaired microvascular reactivity in post-COVID-19 syndrome is independent of cardiorespiratory fitness.},
journal = {American journal of physiology. Regulatory, integrative and comparative physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpregu.00050.2026},
pmid = {42133310},
issn = {1522-1490},
support = {MR/S028188/1//Ministerium f&#xfc;r Wissenschaft, Forschung und Kunst Baden-W&#xfc;rttemberg (MWK)/ ; },
abstract = {Current evidence demonstrates that patients that suffer from long-term SARS-CoV-2 symptoms (i.e., post-COVID-19 syndrome, PCS) often present muscle fatigue and dyspnea. This is discussed to be a result of vascular dysfunction and oxidative stress triggered by the infection. However, its effects on the microvasculature remains unknown. 62 participants (61.3% women) were recruited (50.0±11.8 yr, body mass index (BMI) 27.6±5.3 kg·m[-2], maximal oxygen uptake (V̇O2max) 26.2±9.4 mL·kg[-1]·min[-1]) from the EPILOC (Epidemiology and clinical characteristics of PCS) phase 2 study. Participants were divided into either a case group (patients with new or prolonged symptoms and impaired general health or work ability compatible with persistent PCS) or control group (symptom-free age-sex matched patients with uneventful recovery after COVID-19). The brachial-ankle pulse wave velocity (baPWV) was assessed via BOSO-ABI system100. To evaluate the microvascular function, a tissue oxygen saturation (StO2) reperfusion rate assessment using near-infrared spectroscopy was performed on the flexor digitorum superficialis muscle. No significant statistical differences were observed between the case and control groups in age, BMI, and baPWV (p>0.05). The control group achieved a greater V̇O2max than the case group (p=0.02). After adjusting for V̇O2max, a significant effect of group (F (1,52) =5.28, p=0.026) in microvascular function was observed, with the case group presenting lower values than the control group ((?)=-0.53, p=0.02). No a priori power calculation was performed - post-hoc sensitivity analysis indicated a minimum detectable effect of Cohen's d=0.72, and secondary outcomes should be interpreted cautiously. Our results indicate a reduced microvascular function in patients with PCS, as compared with the control group. Such impairment may be linked to the prolonged symptoms experienced by patients, causing capillary flow disturbance and, subsequently, limiting muscle oxygen uptake.},
}
@article {pmid42119693,
year = {2026},
author = {Schomerus, G and Nicolas, ML and Fritz, F and Schneider, D and Büchner, R},
title = {[What is the Role of "the Psyche"? Long COVID and ME/CFS as Test Cases for Evidence-Based and Patient-Centered Psychiatry and Psychotherapy].},
journal = {Psychiatrische Praxis},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2866-9127},
pmid = {42119693},
issn = {1439-0876},
abstract = {The role of psychological factors in the development and course of Long Covid (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a subject of controversial debate. We argue that psychologizing LC and ME/CFS carries significant risks: it leads to potentially harmful therapies, invalidates the patients' experience of illness, hinders effective interventions such as pacing, diverts focus from necessary physical diagnostics and treatment, disadvantages patients in medical assessments, and places a considerable additional burden on the families of affected children or other relatives. We show that many of the arguments presented for a psychological contribution are nonspecific or insufficiently supported by empirical evidence. Our essay therefore advocates for extreme caution in attributing psychological factors to these conditions, in the interest of a specific, evidence-based, and patient-centered psychiatry and psychotherapy.},
}
@article {pmid42120715,
year = {2026},
author = {Tatai, O and Nagy, S and Nguyen, THT and Tóth, BL and Antal-Szalmás, P and Siket, IM and Pintér, TB and Fagyas, M and Papp, Z and Csécsei, P and Lehoczki, A and Szappanos, &#xc1; and Ungvari, Z and Molnár, T and Tóth, A},
title = {Tissue-specific autoantibody signatures reveal immune alterations undetected by routine serology in long COVID.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42120715},
issn = {2509-2723},
support = {Advanced 152363//National Research, Development and Innovation Fund of Hungary/ ; TKP2021-NKTA-47//National Research, Development and Innovation Fund of Hungary/ ; National Cardiovascular Laboratory Program (RRF-2.3.1-21-2022-00003)//National Research, Development and Innovation Fund of Hungary/ ; Project no. 135784//National Research, Development and Innovation Fund of Hungary/ ; K20 funding scheme//National Research, Development and Innovation Fund of Hungary/ ; the European University for Well-Being (EUniWell) program (grant agreement number: 101004093/ EUniWell/EAC-A02-2019 / EAC-A02-2019-1)//National Research, Development and Innovation Fund of Hungary/ ; EK&#xd6;P-24-2 University Research Scholarship Program of the Ministry for Culture//National Research, Development and Innovation Fund of Hungary/ ; Innovation//National Research, Development and Innovation Fund of Hungary/ ; 2015-1.2.1.-HU-RIZONT-2-25-00016 (INNOBRAIN)//National Research, Development and Innovation Office of Hungary/ ; Mission-driven National Cardiovascular Laboratory Program (2026)//National Research, Development and Innovation Office of Hungary/ ; },
abstract = {Long COVID affects a substantial proportion of individuals recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet its underlying pathophysiology remains poorly understood. Although autoimmunity is increasingly implicated in disease pathogenesis, routine diagnostics frequently fail to detect relevant immune dysregulation. To address this gap, we analyzed sera from Long COVID patients (n = 114) and pre-pandemic controls (n = 36) using tissue-based Western blotting targeting cardiac, pulmonary, and vascular antigens, alongside standard ANA HEp-2 testing. Longitudinal samples were additionally evaluated to assess autoantibody dynamics. Autoantibodies were detected in the majority of patients (83% vs. 53% in controls; p < 0.05), showing a dominant cardiovascular pattern. While cardiac (54% vs. 33% in controls; p = 0.16) and pulmonary (34% vs. 30% in controls; p = 0.50) prevalences did not reach significance, vascular autoreactivity was markedly elevated in Long COVID (34% vs. 8% in controls; p < 0.05). Responses exhibited broad polyreactivity and IgM dominance, with longitudinal follow-up showing persistent IgM and the emergence of additional isotypes. Clinically, cardiac autoreactivity was associated with hypertension and headache, while the overall autoreactivity correlated with anosmia and ageusia. In contrast, ANA HEp-2 testing showed no discriminatory value or clinical associations. Distinct autoreactivity patterns further aligned with female sex and clinical parameters (C-reactive protein, creatinine, troponin, body mass index). Together, these findings reveal a high burden of tissue-specific autoantibodies invisible to standard ANA screening. This persistent, IgM-skewed profile suggests ongoing immune dysregulation and may reflect a previously underrecognized component of the immunological response in long COVID, highlighting the need for targeted immunodiagnostic approaches beyond routine serology.},
}
@article {pmid42121112,
year = {2026},
author = {Jovicic, F and McCracken, LM and Rozental, A and Buhrman, M},
title = {Impacts of Post-Covid Condition (PCC) in Sweden: a cross-sectional observational survey study.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {},
pmid = {42121112},
issn = {1471-2458},
mesh = {Humans ; Sweden/epidemiology ; Female ; *COVID-19/psychology/complications/epidemiology ; Male ; Cross-Sectional Studies ; Middle Aged ; Adult ; Aged ; Surveys and Questionnaires ; Fatigue/epidemiology ; Quality of Life ; Young Adult ; },
abstract = {BACKGROUND: The COVID-19 pandemic left many people with persistent health problems following a COVID-19 infection. Research on the condition better known as Post-Covid Condition (PCC) is still inconclusive, and few evidence-based treatments are currently available, although several studies report promising results. There are however people in need of treatment and support.<br><br>METHODS: To better understand what such help might entail, we conducted an online-based survey (n&#x2009;=&#x2009;629, 82.6% women) to examine the impact of PCC in Sweden and explore relationships among various variables using correlation analysis. Swedish-speaking adults with at least one persisting health problem after COVID-19 were included in the study. The survey included demographic and psychosocial variables, historic COVID-19 data, other clinical measures of psychological distress, satisfaction with life, and daily functioning impairment.<br><br>RESULTS: Results indicate a substantial and heterogeneous impact of PCC in this sample. Participants reported an average of 10.70 (SD&#x2009;=&#x2009;5.62) symptoms with the most frequently reported being fatigue (90.9%, n&#x2009;=&#x2009;507) and cognitive deficits (73.3%, n&#x2009;=&#x2009;409). The highest average symptom burden scores were reported for post-exertional malaise (PEM; M&#x2009;=&#x2009;8.37, SD&#x2009;=&#x2009;1.70) and fatigue (M&#x2009;=&#x2009;8.22, SD&#x2009;=&#x2009;1.77). Medication, self-help advice, and physiotherapy were the most frequently reported treatment modalities. Most participants reported their problems being unchanged or improved after treatment, but there were reports of worsening as well. Regarding psychological distress, participants reported mild anxiety, moderate depression, and subclinical but notable levels of sleeping problems. On average, daily functioning was substantially impaired by PCC and participants reported being "somewhat dissatisfied with life". The correlational analyses revealed several significant correlations (|r| = 0.11-0.93, p < .01), with strongest relationships between the clinical variables.<br><br>CONCLUSIONS: While this study aimed to measure impacts of PCC in many different areas of life, it holds some limitations, and there are many questions remaining. We present several recommendations for methodology and future research topics. Identifying modifiable variables that can be used in developing a treatment is naturally a next step. Based on empiric evidence from similar conditions, psychological flexibility (PF) may be a promising one.},
}
@article {pmid42121889,
year = {2026},
author = {Kopańska, M and Trojniak, J and Góral-Półrola, J and Pąchalska, M},
title = {Alterations in Cortical Oscillatory Dynamics Following SARS-CoV-2 Infection: QEEG Biomarkers of Vulnerability to Attention and Seizure-Related Symptoms.},
journal = {Cells},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/cells15090790},
pmid = {42121889},
issn = {2073-4409},
mesh = {Humans ; *COVID-19/complications/physiopathology ; *Electroencephalography/methods ; *Seizures/physiopathology/etiology ; Biomarkers/metabolism ; SARS-CoV-2 ; *Attention/physiology ; *Cerebral Cortex/physiopathology ; },
abstract = {SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens.},
}
@article {pmid42123618,
year = {2026},
author = {Wirth, KJ and Scheibenbogen, C},
title = {Imbalance of Excitatory and Inhibitory Neurotransmitter Systems in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {International journal of molecular sciences},
volume = {27},
number = {9},
pages = {},
doi = {10.3390/ijms27094041},
pmid = {42123618},
issn = {1422-0067},
mesh = {Humans ; *Fatigue Syndrome, Chronic/metabolism/physiopathology ; *Neurotransmitter Agents/metabolism ; *COVID-19/metabolism/complications ; SARS-CoV-2 ; Synaptic Transmission ; Animals ; },
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID-19 syndrome share a symptom profile, including severe fatigue, cognitive dysfunction, exertional intolerance, sleep disturbances, hypervigilance, and the paradoxical state of being "wired but tired." A well-established finding is sympathetic hyperactivity with reduced vagal tone, typically interpreted as autonomic nervous system dysfunction. Emerging evidence, however, suggests a broader disturbance across multiple neurotransmitter systems. This paper reviews current knowledge on neurotransmitter systems implicated in ME/CFS and Long COVID, focusing on potential mechanisms of dysregulation and their roles in disease pathology and symptom generation, as well as implications for treatment. In addition to abnormalities of the noradrenergic system, disturbances in serotonergic, GABAergic, and glutamatergic signaling have been reported. Contributing factors may include autoimmunity, neuroinflammation, gut dysbiosis, epigenetic influences, and stressors such as orthostatic intolerance, metabolic strain, and pain. A shift favoring excitatory over inhibitory neurotransmission can lead to excessive neural activation, autonomic dysfunction, sensory hypersensitivities, sleep disturbances, and cognitive impairment. Reduced GABAergic tone combined with increased glutamatergic and noradrenergic activity may elevate skeletal muscle tone, contributing to calcium overload, mitochondrial dysfunction, exertional intolerance, and post-exertional malaise. Various pharmacological treatments may partially rebalance these neurotransmitter systems, but limited efficacy highlights the need for systematic investigation and individualized strategies.},
}
@article {pmid42127260,
year = {2026},
author = {Antar, AAR},
title = {CROI 2026: Acute and Postacute COVID-19.},
journal = {Topics in antiviral medicine},
volume = {34},
number = {2},
pages = {494-500},
pmid = {42127260},
issn = {2161-5853},
mesh = {Humans ; *COVID-19/complications/immunology/therapy ; SARS-CoV-2/immunology ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Antibodies, Monoclonal/therapeutic use ; },
abstract = {The 2026 Conference on Retroviruses and Opportunistic Infections (CROI) furthered our understanding of acute COVID-19, long COVID, postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viral immunity, and SARS-CoV-2 therapeutics. Results of a first-in-human validation study of DNA-encoded monoclonal antibody (DMAb) technology demonstrated safety and robust and durable monoclonal antibody (mAb) production, giving the green light to further develop the DMAb platform. Pemivibart administration to people with advanced HIV was well tolerated and associated with good levels of neutralizing antibodies. A new pan-coronavirus 3C-like protease inhibitor was shown to have similar pharmacokinetics and a similar safety profile in people with renal impairment and people with hepatic impairment. A study of SARS-CoV-2 infections in 2023 demonstrated continued risk for new incident diagnoses and worsening of prior comorbidities in the year after infection. SARS-CoV-2 infection in people with HIV is associated with discernible decline in estimated glomerular filtration rate in the 2 years after infection. A blinded study of circulating SARS-CoV-2 antigen found no association between the presence of antigen and the likelihood of having long COVID. Most people with long COVID in a cohort study have experienced stigma or feeling dismissed in interactions with their clinicians.},
}
@article {pmid42112321,
year = {2026},
author = {Bentebbal, S and Zaqout, A and Meqbel, B and Bensmail, I and Aldushain, A and de la Fuente, A and Thomas, R and Naik, A and Shaath, H and Al-Akl, NS and Adam, A and Moussa, HYA and Shin, KC and Taha, RZ and Abukhattab, M and Al-Maslamani, MA and Alajez, NM and Arredouani, A and Park, Y and Abdulla, SA and El-Agnaf, OMA and Abdesselem, HB and Omrani, AS and Decock, J},
title = {Post-booster longitudinal plasma proteomic changes following BNT162b2 COVID-19 vaccination in Qatar.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1762522},
pmid = {42112321},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/prevention &amp; control/immunology/blood ; Male ; *BNT162 Vaccine/immunology ; Adult ; Longitudinal Studies ; Female ; *SARS-CoV-2/immunology ; Proteomics ; *Proteome ; Middle Aged ; Qatar ; *Immunization, Secondary ; Young Adult ; Vaccination ; },
abstract = {BACKGROUND: The COVID-19 pandemic imposed a major global health and economic burden. Although the pandemic was no longer declared a public health emergency of international concern in May 2023, SARS-CoV-2 variants continue to emerge, and millions remain affected by long COVID. This raises the question whether continued vaccination provides lasting benefits in preventing viral transmission and severe illness.<br><br>AIM: This longitudinal study assessed the effects of the third BNT162b2 mRNA vaccine dose on the circulating proteome for 6 months.<br><br>METHODS: Plasma levels of 354 unique proteins were quantified before, and at 3- and 6-months post-booster using Olink technology in 70 healthy individuals; 35 infection-na&#xef;ve and 35 previously infected individuals (18 infected before, 17 after completing the two-dose regimen).<br><br>RESULTS: Infection-na&#xef;ve individuals showed altered levels of eleven and eight proteins at 3- and 6-months post-booster, respectively, including a significant sustained increase in PARP-1 (FC&#xa0;=&#xa0;1.53, p=8.59x10[-5], pFDR=0.01) and significant decrease in MMP-7 (FC&#xa0;=&#xa0;0.68, p=4.58x10[-5], pFDR=0.01), in addition to elevated levels of MMP-1 (FC&#xa0;=&#xa0;1.46, p=0.04, pFDR>0.05) and decrease in 4E-BP1 (FC&#xa0;=&#xa0;0.58, p=0.01, pFDR>0.05) at 6 months post-booster. Similarly, previously infected individuals, in particular those with earlier infections before receiving the second dose exhibited a significant sustained upregulation of PARP-1 (FC&#xa0;=&#xa0;2.10, p=1.19x10[-5], pFDR=0.003) and downregulation of MMP-7 (FC&#xa0;=&#xa0;0.58, p=2.19x10[-5], pFDR=0.003) at 6-months post-booster. Notably, PARP-1 and MMP-7 were consistently affected across all individuals. Longitudinal proteome profiling revealed dysregulation of key inflammatory proteins for up to 6 months post-booster, including PARP-1 and MMP-7 (pFDR=1.58x10[-8] and pFDR=1.59x10[-5], respectively).<br><br>CONCLUSIONS: These findings provide insights into the temporal dynamics of circulating proteomic responses following booster vaccination, highlighting molecular features that may be relevant to immune readiness and post-vaccination inflammatory processes.},
}
@article {pmid42114957,
year = {2026},
author = {Järvholm, K and Bygdell, M and Dreifaldt, J and Åkesson, E and Lundberg, T},
title = {"It's sad, and I want to go back to how things were before": a qualitative study of young people's experiences of living with long COVID.},
journal = {BMJ paediatrics open},
volume = {10},
number = {1},
pages = {},
doi = {10.1136/bmjpo-2025-004167},
pmid = {42114957},
issn = {2399-9772},
mesh = {Humans ; Female ; Male ; *COVID-19/psychology/complications ; Qualitative Research ; Adolescent ; Sweden/epidemiology ; Child ; Adaptation, Psychological ; SARS-CoV-2 ; Interviews as Topic ; Quality of Life ; Chronic Disease/psychology ; },
abstract = {BACKGROUND: Long COVID is a newly recognised condition that also affects children and young people (CYP). However, little is known about how it impacts their daily lives and well-being from their own perspective. This study aimed to explore the lived experiences of CYP living with long COVID.<br><br>METHODS: Swedish-speaking CYP who developed long COVID before the age of 18 years were invited to participate in semistructured interviews. Between February and September 2024, seven CYP (four girls and three boys) participated (mean interview duration=51&#x2009;min). Data were analysed using reflexive thematic analysis to identify codes and then themes with related subthemes.<br><br>RESULTS: Two main themes were generated. The first main theme 'I am stumbling in the dark: Living with unpredictability and limitations' covers how CYP were affected by the consequences of long COVID. The subtheme 'How do I live and function now?' illustrates how the CYP tried to navigate the disabling and yet fluctuating symptoms, and the subtheme 'Who am I now?' represents the identity-related consequences. The second main theme 'Navigating responses from others to find support' illustrates how others have responded to their symptoms and how these responses were perceived by the CYP. The subthemes 'Stop being sceptical!', 'Just try to help me!' and 'Accept and validate me!' illustrate interactions perceived as invalidating or disrespectful, what has been experienced as helpful or unhelpful and the kinds of support adolescents have valued.<br><br>CONCLUSIONS: Long COVID negatively impacted the CYP's lives, affecting their relationships, education, leisure activities and sense of identity. Dismissive and sceptical attitudes from professionals and peers substantially increased the burden, whereas encountering acceptance and knowledgeable professionals facilitated coping with long COVID.},
}
@article {pmid42115979,
year = {2026},
author = {Mazzali, C and Magnoni, P and Valsecchi, MG and Vigani, D and Lucifora, C and Russo, AG and , },
title = {Incident diabetes within the first two years after SARS-CoV-2 infection: a population-based retrospective cohort study of the Agency for Health Protection of Milan, Italy.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13467-4},
pmid = {42115979},
issn = {1471-2334},
support = {2021-4388//Fondazione Cariplo/ ; },
abstract = {BACKGROUND: Postacute sequelae of SARS-CoV-2 infection (PASC), including persistent symptoms and acute and chronic diagnoses, have become a major research focus. Diabetes mellitus, beyond its established link to COVID-19 severity, is increasingly recognized as a potential long-term outcome. This study investigated the association between SARS-CoV-2 infection and incident diabetes using population-level health administrative data (HAD) from the Agency for Health Protection of Milan, where the epicenter of the pandemic in Italy took place.<br><br>METHODS: This retrospective cohort study included adult residents without a history of diabetes who underwent SARS-CoV-2 testing between 1 March and 31 December 2020. Test-positive individuals were matched 1:1 to test-negative individuals based on sex, age, and testing week. The cohort was followed through 31 December 2021. The incidence of diabetes, identified using an HAD-based case-detection algorithm, was compared between the two groups, and in stratified analyses by sex and age, using weighted Cox models adjusted for chronic comorbidities, area-level deprivation, influenza and pneumococcal vaccinations. Weights were calculated via the inverse probability weighting approach. Effect estimates are presented as hazard ratios (HRs).<br><br>RESULTS: Our final cohort included 248,176 residents (124,026 test-negative, 124,150 test-positive). Over a median follow-up time of 415 days, 739 positive (0.60%) and 657 negative (0.53%) individuals were newly identified with diabetes. The incidence among positive individuals was 572.82 per 100,000 person-years (CI 531.52-614.12), and that among negative individuals was 509.50 per 100,000 person-years (CI 470.54-548.46). The overall HR was 1.13 (CI 1.02-1.25). In stratified analyses, this effect was prominent in women aged 41-60 years (HR 1.31; CI 1.02-1.68).<br><br>CONCLUSIONS: This study provides population-based evidence supporting an association between SARS-CoV-2 infection and newly detected diabetes. These findings contribute to understanding the long-term health impact of COVID-19 and may inform public health strategies for PASC prevention and management.},
}
@article {pmid42116095,
year = {2026},
author = {Thölking, T and Müller, F and Riester, T and Lampe, V and Theil, LM and Hummers, E and Sarpari, K and Dopfer-Jablonka, A and Happle, C and Steffens, S and Meier-Maiwald, M and Mikuteit, M and Schröder, D},
title = {Impact of post-exertional malaise frequency and fatigue in Long COVID patients on health-related quality of life.},
journal = {Health and quality of life outcomes},
volume = {24},
number = {1},
pages = {},
pmid = {42116095},
issn = {1477-7525},
mesh = {Humans ; *Quality of Life/psychology ; Male ; Female ; *Fatigue/etiology/psychology/epidemiology ; Cross-Sectional Studies ; Middle Aged ; *COVID-19/complications/psychology ; Germany/epidemiology ; Adult ; Aged ; SARS-CoV-2 ; Severity of Illness Index ; Surveys and Questionnaires ; },
abstract = {PURPOSE: The aim of this study was to investigate the impact of post-exertional malaise (PEM) frequency and PEM severity on health-related quality of life (HRQoL) among individuals with Long COVID.<br><br>METHODS: We conducted a cross-sectional online survey including adults in Germany with self-reported Long COVID and PEM. Fatigue severity was assessed with the Fatigue Assessment Scale (FAS), and HRQoL was measured using the EQ-5D-3L (descriptive index and visual analogue scale [EQ-VAS]). Associations between PEM frequency, fatigue, and HRQoL were examined using correlations and non-parametric group comparisons. Multiple linear regression models were fitted to predict HRQoL while controlling for age, sex, employment status, and subjective social status.<br><br>RESULTS: Higher PEM frequency was associated with significantly lower EQ-5D index scores (&#x3c1; = -&#x2009;0.32, p<.001). PEM severity was also strongly correlated with reduced HRQoL (EQ-5D index: &#x3c1; = -&#x2009;0.43, p<.001). In multivariable regression models, greater fatigue and higher PEM frequency independently predicted poorer HRQoL, even after adjustment for sociodemographic factors.<br><br>CONCLUSION: Both PEM frequency and PEM severity substantially impair HRQoL in individuals with Long COVID. These findings underscore the clinical relevance of PEM as a key symptom and highlight the need for targeted management strategies to mitigate its impact on daily life.<br><br>CLINICAL TRIAL NUMBER: German Clinical Trials Register DRKS00026007; registration date: 9 September 2021.},
}
@article {pmid42116147,
year = {2026},
author = {Fonka, CB},
title = {Perspectives of senior health managers on COVID-19 response and challenges, lessons learned and opportunities against future outbreaks in Gauteng province, South Africa.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14635-7},
pmid = {42116147},
issn = {1472-6963},
abstract = {BACKGROUND: This study explores senior health managers' perspectives on COVID-19 response and challenges, lessons learned, and opportunities in Gauteng, one of the most affected provinces in South Africa, and further presents recommendations for health systems strengthening, preparedness, and effective response against future infectious outbreaks or pandemics.<br><br>METHOD: Using a qualitative exploratory study, online in-depth interviews were conducted with purposively selected senior managers from the Gauteng Department of Health (GDoH) who were at the forefront of managing the pandemic. Recordings were transcribed verbatim, and saturation was reached with thirteen interviewees (n&#x2009;=&#x2009;13). Thematic and inductive analyses were performed in NVivo 10 and reported following the Consolidated Criteria for Reporting Qualitative Research (COREQ).<br><br>RESULTS: The findings are presented in four main themes, namely: GDoH's response to the COVID-19 pandemic, COVID-19-related challenges, lessons learned and opportunities from COVID-19, and participants' recommendations on dealing with future pandemics. The managers' perspectives suggest that GDoH's response to COVID-19 was comprehensive, multi-sectoral, and effective through public awareness, the War Room/nerve Centre that managed the response, resources mobilization like the recruitment of additional nurses and doctors, and vaccination. The challenges included the adverse effects of "long-COVID" and mental health, demised health workers, corruption and embezzlement of COVID-19 funds, high cost of living, and gender-based violence associated with COVID-19. The lessons learned included the importance of technology, surveillance, and data analytics during crises, improved hygiene-like hand washing, to mitigate infection transmission, and the urgency to build resilient health systems. The pandemic also highlighted the need for inclusive and collaborative public-private partnerships in the National Health Insurance (NHI) implementation. Participants' recommendations for dealing with future outbreaks included improvements in ICT, the need for social media regulation, working remotely, pandemic incentives for health workers, improved and accountable leadership, addressing corruption and the need for further COVID-19 research.<br><br>CONCLUSION: According to the health managers interviewed in this study, the GDoH response to COVID-19 appeared to be resilient, comprehensive, multi-sectoral and effective despite the challenges emanating from the pandemic. Although the pandemic harmed the health system, lessons were learned with opportunities for leveraging the impact of future outbreaks, particularly as South Africa is in the process of providing universal health coverage, pronounced through the NHI.<br><br>CLINICAL TRIAL REGISTRATION: Not applicable.},
}
@article {pmid42117068,
year = {2026},
author = {Rivas, JC and Restrepo, A and Barbosa, MM and Cordoba-Melo, BD and Arteaga-Tobar, AA and Naranjo-Ramirez, MC and Ochoa-Rojas, MC and Miranda-Bastidas, CA and Casanova Rojas, AF and Mina Sánchez, AF and Tovar Cuevas, JR and Gómez-Mesa, JE},
title = {Factorial structure of the patient health questionnaire-9 in long-term survivors of severe COVID-19.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1657877},
pmid = {42117068},
issn = {1664-1078},
abstract = {INTRODUCTION: Depression is prevalent among survivors of severe COVID-19, yet psychometric evidence for screening instruments in this population remains limited, particularly in Latin America. The factor structure of the Patient Health Questionnaire-9 (PHQ-9) remains unclear in long-term survivors of severe COVID-19. This study aimed to evaluate the psychometric properties and factor structure of the PHQ-9 in a Colombian cohort of long-term survivors of severe COVID-19.<br><br>MATERIALS AND METHODS: The PHQ-9 was administered to 177 individuals previously hospitalized with severe COVID-19, with follow-up extending up to 20&#x202f;months post-discharge. Both exploratory (EFA) and confirmatory factor analyses (CFA) were conducted to evaluate competing structural models.<br><br>RESULTS: The unifactorial solution demonstrated superior internal consistency (&#x3b1;&#x202f;=&#x202f;0.81, &#x3c9;&#x202f;=&#x202f;0.86) compared with the two-factor solution (Factor 1: &#x3b1;&#x202f;=&#x202f;0.74; Factor 2: &#x3b1;&#x202f;=&#x202f;0.61). The two-factor item distribution did not correspond to established depression frameworks. CFA showed both models had acceptable fit, but chi-square difference testing revealed no significant improvement for the two-factor model (&#x394;&#x3c7;[2]&#x202f;=&#x202f;0.27, p&#x202f;=&#x202f;0.602). The fatigue item exhibited the lowest factor loading.<br><br>CONCLUSION: The PHQ-9 demonstrated a predominantly unidimensional structure in this population. The weak performance of the fatigue item suggests potential overlap between long COVID-related fatigue and depressive symptomatology, warranting future criterion validation against structured psychiatric assessment.},
}
@article {pmid42040960,
year = {2026},
author = {Valverde, A and Capistrano, K and Naqvi, RA and Elshourbagy, S and Etminan, S and Sandoval, G and Bambrilla, M and Nares, S and Shukla, D and Schwartz, J and Naqvi, A},
title = {Periodontitis Primes the Oral Microenvironment for PS-Dependent Non-Canonical Entry Pathways Linked to SARS-CoV-2 Susceptibility.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42040960},
issn = {2693-5015},
abstract = {SARS-CoV-2 infection extends beyond the respiratory tract, with the oral cavity emerging as a critical site of viral activity shaped by epithelial receptor expression, microbial interactions, and inflammatory status. Periodontal disease (PD), a chronic dysbiotic condition, may heighten susceptibility to SARS-CoV-2 through inflammation-driven upregulation of non-canonical viral entry pathways. In this study, we investigated genes in the phosphatidylserine (PS)-dependent pathway, including ADAM17, ATP11c, TIM1, TIM3, and TIM4, in gingival tissue, saliva, and oral keratinocytes to define how PD and SARS-CoV-2 coordinately modulate oral viral entry mechanisms. Prepandemic gingival biopsies revealed significant upregulation of all non-canonical receptors in inflamed tissue, indicating that PD alone establishes a permissive molecular environment for PS-mediated microbial entry. In a post-vaccination cohort, salivary expression of these receptors was markedly elevated in COVID-19-positive individuals with PD, accompanied by significantly increased salivary PS levels, suggesting synergistic effects of viral exposure and periodontal inflammation. In vitro co-infection of primary human oral keratinocytes with SARS-CoV-2 and periodontal pathogens (P. gingivalis, A. actinomycetemcomitans) induced robust, synergistic activation of PS-dependent entry genes, particularly TIM family receptors. Together, these findings identify PS and its associated receptors as inflammation-responsive mediators that expand SARS-CoV-2 entry routes in the oral mucosa. This work highlights a mechanistic intersection between COVID-19 and periodontal disease, with implications for viral persistence, immune dysregulation, and long-term oral health outcomes.},
}
@article {pmid42107843,
year = {2026},
author = {Floridia, M and Weimer, LE and Lo Forte, A and Palange, P and Agostoni, P and Ciardi, MR and Tosato, M and Lacedonia, D and Gnerre, P and Barisione, E and Martino, GP and Vagheggini, G and Onder, G and , },
title = {Dyspnea and fatigue in Long-COVID: definition of risk factors and of DLCO-based phenotypes in a multicenter study of 765 patients from Italy.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108880},
doi = {10.1016/j.rmed.2026.108880},
pmid = {42107843},
issn = {1532-3064},
abstract = {BACKGROUND: Dyspnea and fatigue represent common Long-COVID symptoms, but their presence is not always accompanied by lung function abnormalities. Aim of the study was to evaluate dyspnea and fatigue in relation to pulmonary function and exercise capacity.<br><br>METHODS: Multicenter cohort study. Multivariable analyses were used to characterize, for both symptoms, functional phenotypes with and without pulmonary impairment according to the diffusing lung capacity for carbon monoxide (DLCO). Exercise capacity was assessed through the distance walked in 6 minutes (6MWD).<br><br>RESULTS: Among 765 patients evaluated at a mean interval of six months from COVID-19, rates of dyspnea and fatigue were 41.3% and 41.6%, respectively. Roughly half of the patients with these two symptoms (51.6% and 54.7%, respectively) had normal pulmonary function at DLCO testing (&#x2265;80% of predicted). Low-DLCO (<80%) dyspnea was significantly associated with female sex, anxiety, duration of hospitalisation, use of corticosteroids and of monoclonal neutralizing antibodies, and its risk decreased at the increasing in time from acute infection. Normal-DLCO dyspnea was associated with younger age and obesity. Low-DLCO fatigue was associated with female sex, heart failure, anxiety and use of corticosteroids. Normal-DLCO fatigue was not associated with demographics, comorbidities, or COVID-19 severity. For both symptoms, the low-DLCO phenotypes had a significantly lower 6MWD.<br><br>CONCLUSIONS: The clinical phenotypes of dyspnea and fatigue with normal pulmonary function should be further explored, possibly with additional tests that assess cardiorespiratory and cardiovascular function. DLCO testing should be included in the evaluation of patients who report dyspnea and/or fatigue as possible Long-COVID symptoms.},
}
@article {pmid42108247,
year = {2026},
author = {Yamamoto, S and Kurano, M and Okamoto, K and Kubota, M and Tsutsumi, T and Aoki, J and Moriya, K},
title = {Sphingolipid and glycerophospholipid profiling in post-acute sequelae of SARS-CoV-2 infection.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-50505-2},
pmid = {42108247},
issn = {2045-2322},
abstract = {Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) is a heterogeneous multisystemic condition with unclear pathogenesis. Emerging evidence suggests that the disruption in metabolism, including lipid metabolism, can be involved in the pathogenesis of coronavirus disease 2019 (COVID-19). We previously measured the bioactive lipids in acute COVID-19, and we hypothesized that bioactive lipid dysregulation play a role in PASC pathogenesis. We conducted targeted LC-MS/MS analysis of sphingolipids and glycerophospholipids in serum samples from individuals with acute-phase COVID-19, including those who developed PASC, alongside healthy controls. We systematically examined lipidomic changes in serum samples, including analyses using linear mixed model, and found that no sphingolipid or glycerophospholipid species differed between the COVID-19 and PASC groups. Although these results are exploratory, the group x time interaction in the linear mixed model suggested that phosphatidylglycerol (PG) may represent a bioactive lipid distinguishing the COVID-19 and PASC groups. Given the small PASC sample size and that the signal was detected only at specific time points, these findings are hypothesis generating and should be confirmed in larger, adequately powered, and independently validated cohorts.},
}
@article {pmid42108528,
year = {2026},
author = {Mosha Miller, SA and Hicar, MD and Berry, CS and Anderson, KB and Lindo, JF and Morse, GD and Christie, CDC},
title = {Long COVID-19 in Hospitalized and Ambulatory Children in Jamaica.},
journal = {The Pediatric infectious disease journal},
volume = {},
number = {},
pages = {},
doi = {10.1097/INF.0000000000005259},
pmid = {42108528},
issn = {1532-0987},
abstract = {This retrospective observational cohort study evaluated acute illness predictors of pediatric Long coronavirus disease 2019 in Jamaica. Poisson regression modeling associated acute univariate symptoms of vomiting, abdominal pain, ageusia, anosmia, fatigue, confusion, brain fog, and multisystem inflammatory syndrome in children and multivariable composite predictors of multisystem inflammatory syndrome in children, vomiting and ageusia. The 47.3% incidence supports the need for improvements in similar resource-constrained settings.},
}
@article {pmid42108714,
year = {2026},
author = {Jang, E and Nan, Y and Chang, H and Young, LE},
title = {Disentangling the Network Structure of Online Social Support: A Multilayer Network Analysis of a Twitter Long COVID Community.},
journal = {Health communication},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/10410236.2026.2672056},
pmid = {42108714},
issn = {1532-7027},
abstract = {Online social support has been shown to be an important resource for people experiencing chronic illnesses. Although numerous studies have examined online support communities, few have conducted in-depth analyses grounded in social network theory and methodologies. To address this gap, this study investigates the types of support and the overall patterning of such exchanges (i.e., the network structure) on Twitter (now X), focusing on a community of people who seek and provide support for Long COVID. Using an exhaustive keyword-based corpus of Long COVID tweets (N = 19,196) collected from August 1-31, 2021, we identified two types of social support shared in this community-informational and emotional-through human annotation combined with supervised machine learning. Conducting descriptive and stochastic social network analysis, we examined how exchanges of each type of support were structured. We focused on the density, reciprocity, and centralization of support ties-three structural features shown to be related to specific types of support. Our results showed that informational support was more prevalent than emotional support. Additionally, these informational and emotional support networks tended to be both reciprocal and concentrated around a small number of central users who received considerable support (i.e., were centralized). Our findings suggest that online health communities hosted on platforms such as Twitter may be better suited for informational support. We also observed that central actors play an important role in facilitating these exchanges. These findings provide practical insights for effective social network interventions.},
}
@article {pmid42109469,
year = {2026},
author = {Cardenas-Jara, AR and Ongaya, A and Shiluli, C and Ramos, LB and Senador, LC and Flores, JA and Kanoi, BN and Reijneveld, JF and Ruvalcaba, A and Perez, D and Waiganjo, P and Lindestam-Arlehamn, CS and Henrich, TJ and Peluso, MJ and Leon, SR and Gitaka, J and Suliman, S},
title = {Prevalence of Long COVID in Mycobacterium tuberculosis-exposed groups.},
journal = {Journal of clinical tuberculosis and other mycobacterial diseases},
volume = {44},
number = {},
pages = {100610},
pmid = {42109469},
issn = {2405-5794},
abstract = {OBJECTIVES: Long COVID (LC), i.e. the persistence of new or worsening symptoms for 3 months after Severe Acute Respiratory Syndrome of Coronavirus 2 (SARS-CoV-2) infection, is an emerging global health burden. The prevalence of LC remains poorly characterized in low- and middle-income countries (LMICs), where other respiratory diseases, like tuberculosis (TB), are prevalent. We aimed to address this gap in Mycobacterium tuberculosis (Mtb)-exposed populations in Peru.<br><br>METHODS: We recruited people with TB (n&#xa0;=&#xa0;36) and their asymptomatic household contacts (n&#xa0;=&#xa0;63) in Peru. We collected clinical data using a questionnaire adapted from a United States-based study of LC. Participants were recruited within 2&#xa0;years of SARS-CoV-2 diagnosis.<br><br>RESULTS: In Peru, 41% participants reported LC symptoms. The most common LC symptoms were neurological (e.g., headache) and musculoskeletal (e.g., back pain). We did not detect an association between TB disease or Mtb infection and LC at this sample size. However, the quality-of-life dimensions worsened during the post-COVID period.<br><br>CONCLUSIONS: LC prevalence in Peru aligns with global trends, underscoring significant health burdens. Those with LC reported high levels of musculoskeletal and neurological symptoms, highlighting the need for long-term follow-up and larger studies in different geographic settings to dissect the impact of TB comorbidity on LC.},
}
@article {pmid42109976,
year = {2026},
author = {Ballard, DW and Warton, EM and Skarbinski, J and Siqueiros, MH and Cholleti, SM and Vinson, DR and Mark, DG and Durant, EJ and DiLena, DD and Reed, ME},
title = {The Long Tail of Long COVID-19: Broad and Extensive Increase in Utilization Within an Integrated Healthcare System.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106676},
pmid = {42109976},
issn = {2168-8184},
abstract = {BACKGROUND: The impact of the emergence of Long COVID on healthcare utilization in a U.S. community setting remains underexplored.<br><br>OBJECTIVE: To examine the healthcare utilization of Long COVID patients compared with pre-COVID-19 era controls before and after SARS-CoV-2 infection within a large integrated delivery system.<br><br>METHODS: This was a retrospective cohort study of adult patients with documented SARS-CoV-2 infection (1/1/2021-6/30/2022) in a multi-site Northern California health system. Long COVID diagnosis was defined by at least one encounter with an associated International Classification of Diseases, Tenth Revision code and/or referral to Long COVID specialty care. Utilization outcomes included inpatient/outpatient encounters, laboratory/imaging/functional testing, specialty care referrals/encounters, and medication use. We used propensity-weighted difference-in-differences models adjusted for study month to compare outcomes between baseline and post-SARS-CoV-2 infection (Long COVID window).&#xa0; Results: Among 600,295 patients with 635,230 SARS-CoV-2 episodes, 3,545 met criteria for Long COVID care-seeking. Long COVID patients had higher baseline utilization and greater increases in post-diagnosis utilization in adjusted analyses. After propensity weighting, these differences persisted and were consistent across the study period, particularly in cardiac and pulmonary care. Total encounters per year were 29.9 post and 14.1 pre (Long COVID) versus 17.7 post and 12.5 pre (NO Long COVID). Total annual ED visits per 100 patients were 65.1 post and 38.0 pre (Long COVID) versus 38.0 post and 32.0 pre (NO Long COVID). Annual hospitalizations per 100 patients were 10.5 post and 5.3 pre (Long COVID) versus 7.4 post and 5.5 pre (NO Long COVID).<br><br>CONCLUSION: Long COVID patients had higher healthcare utilization before and after diagnosis, with sharper increases across nearly all outcomes.},
}
@article {pmid42111378,
year = {2026},
author = {Mali, I and Harrison, M and Frizzell, B and Castro, M and McHorse, A and Que, LG and Mummy, D and Niedbalski, PJ},
title = {Using hyperpolarised xenon-129 magnetic resonance imaging to investigate longitudinal effects of long COVID on pulmonary function.},
journal = {ERJ open research},
volume = {12},
number = {2},
pages = {},
pmid = {42111378},
issn = {2312-0541},
abstract = {Hyperpolarised [129]Xe MRI shows significant improvements in VDP and select gas exchange metrics at ∼20 months compared to ∼14 months following initial COVID-19 infection https://bit.ly/3LoJry4.},
}
@article {pmid42103518,
year = {2027},
author = {Philip, KEJ and Owles, H and McVey, S and Pagnuco, T and Bruce, K and Warnock, B and Chomacki, A and Brunjes, H and Mollica, J and Lound, A and Zumpe, S and Abrahams, AM and Padmanaban, V and Hardy, TH and Lewis, A and Lalvani, A and Elkin, SL and Hopkinson, NS},
title = {An online singing-based breathing and wellbeing programme (ENO Breathe) in people with long COVID breathlessness in the UK: a cohort study.},
journal = {The Lancet. Digital health},
volume = {},
number = {},
pages = {100988},
doi = {10.1016/j.landig.2026.100988},
pmid = {42103518},
issn = {2589-7500},
abstract = {BACKGROUND: Post-COVID-19 condition (also known as long COVID) breathlessness is a common, complex, and frequently debilitating problem for which few evidence-based interventions exist. A previous randomised trial found that participation in an online 6-week breathing and wellbeing programme (ENO Breathe), using singing techniques, was associated with improvements in health-related quality of life (HRQOL) and breathlessness. We aimed to assess the impact of this intervention outside a trial setting.<br><br>METHODS: In this cohort study, participants were referred from 51 UK-based National Health Service (NHS) long COVID clinics, where they had been diagnosed with breathlessness due to long COVID. The eligibility criteria of ENO Breathe were age 18 years or older, having long COVID with associated breathlessness, diagnosis and referral from a specialist collaborating NHS long COVID clinic, and access and ability to engage with the online programme. We compared baseline and post-intervention data to assess the effect of the ENO Breathe programme on HRQOL assessed using the RAND-36 Mental and Physical Health Composite (MHC and PHC) primary outcome, with an estimated minimally clinically important difference of 3; breathlessness (assessed using Dyspnoea-12 scores and visual analogue scales [VAS] for breathlessness at rest, walking, using stairs, and running); anxiety (assessed using the Generalised Anxiety Disorder-7 questionnaire [GAD-7]); and respiratory symptoms (assessed using the COPD Assessment Test [CAT]).<br><br>FINDINGS: 1413 programme participants were included in this analysis (mean age 49 years [SD 11&#xb7;9], BMI 28 kg/m[2] [7&#xb7;2]). 1130 (80%) participants were female, 273 (19%) were male, and ten (1%) did not disclose their gender. 1165 (82%) participants were White, 87 (6%) were Asian, 47 (3%) were Black, 48 (3%) were of mixed or multiple ethnic backgrounds, 31 (2%) reported their ethnicity or race as other (ie, not one of the categories specified), and 35 (2%) did not disclose their ethnicity or race. Participants reported having long COVID symptoms for a median of 415 days (IQR 246-601) at the time of registration with the programme. 1188 (84%) of 1413 participants provided follow-up data on completion of the programme. Completing ENO Breathe was associated with improvements in HRQOL (median difference in RAND-36 MHC 2&#xb7;98, IQR -1&#xb7;53 to 8&#xb7;42; and median difference in PHC 1&#xb7;69, -1&#xb7;32 to 5&#xb7;01), breathlessness (mean difference in Dyspnoea-12 -4&#xb7;29, 95% CI -4&#xb7;64 to -3&#xb7;94; VAS breathlessness scores walking median difference -5, IQR -18 to 6; stairs median difference -10, -25 to 3; and running median difference -3, -19 to 0), anxiety (median GAD-7 score difference -1, IQR -4 to 1), and respiratory symptom impact (mean CAT score difference -2&#xb7;50, -2&#xb7;81 to -2&#xb7;19; all p<0&#xb7;0001). The VAS breathlessness score at rest did not significantly change (median difference 0, IQR -10 to 13; p=0&#xb7;24). The response to the ENO Breathe intervention did not differ by age, gender, ethnicity, or pre-existing asthma. There were no reported clinically significant adverse events.<br><br>INTERPRETATION: The ENO Breathe programme can improve HRQOL, breathlessness, anxiety, and respiratory symptoms in people with long COVID and breathlessness. ENO Breathe could be tested in other major causes of breathlessness and might help inform the development and delivery of other related interventions.<br><br>FUNDING: Imperial College London.},
}
@article {pmid42106490,
year = {2026},
author = {Azabou, E and Pillot, A and Bao, G and Mehlal, S and Arnould, A and Agar-Hug, N and Zagdoun, M and Genolini, A and Russo, A and Rangon, CM and Azouvi, P},
title = {Transcutaneous auricular vagus nerve stimulation improves dysautonomia, post-traumatic stress disorder and cognitive impairment in long covid patients: a pilot study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-52582-9},
pmid = {42106490},
issn = {2045-2322},
abstract = {Long COVID is frequently associated with persistent autonomic dysfunction, cognitive impairment, and psychological distress, reflecting sustained neuroimmune and autonomic dysregulation. Effective disease-modifying therapies remain scarce. To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic symptoms, post-traumatic stress symptoms, and cognitive performance in patients with long COVID. In this open-label, single-arm prospective pilot study, seventeen patients with long COVID underwent weekly one-hour taVNS sessions for eight consecutive weeks. Autonomic symptoms were assessed using the Composite Autonomic Symptom Score-31 (COMPASS-31), psychological symptoms using the PTSD Checklist for DSM-5 (PCL-5), and cognitive function using a standardized attention and executive function battery (COGBAT). Outcomes were evaluated at baseline and post-intervention. Paired non-parametric analyses were performed. Following taVNS, autonomic symptoms improved significantly, with mean COMPASS-31 scores decreasing from 33.71 ± 16.81 to 13.78 ± 9.38 (p < 0.0001). Post-traumatic stress symptoms were significantly reduced (PCL-5: 25.76 ± 14.99 to 19.47 ± 14.63; p = 0.028). Cognitive performance improved, with COGBAT scores increasing from 37.71 ± 25.75 to 49.41 ± 26.79 (p = 0.011). No adverse events were reported. taVNS appears to be a safe and promising non-pharmacological intervention for improving autonomic dysfunction, cognitive impairment, and psychological symptoms in long COVID. These findings warrant confirmation in randomized, sham-controlled trials.},
}
@article {pmid42095154,
year = {2026},
author = {Rakab, MS and Mirza, I and Ali, MM and Khan, A and Darbar, D and Mahmoud, AM},
title = {Endothelial and cardiac dysfunction in long COVID With cardiovascular symptoms is associated with imbalance in the ADMA-DDAH-NOx pathway.},
journal = {Frontiers in cardiovascular medicine},
volume = {13},
number = {},
pages = {1802359},
pmid = {42095154},
issn = {2297-055X},
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) commonly feature lingering symptoms of persistent cardiovascular pathology, yet the mechanisms remain incompletely defined. The ADMA-DDAH-NOx axis is a central regulator of endothelial function: ADMA inhibits endothelial NOx synthase, while DDAH clears most circulating ADMA. Although ADMA is linked to acute COVID-19 severity, its regulation in PASC remains largely unknown.<br><br>METHODS: We performed integrated vascular and cardiac phenotyping in 49 RECOVER participants: never-infected controls (n&#x2009;=&#x2009;10), recovered COVID-19 without persistent symptoms (PASC-, n&#x2009;=&#x2009;20), and PASC with persistent cardiovascular-related symptoms lasting &#x2265;12 weeks post-infection (PASC+, n&#x2009;=&#x2009;19). We measured ADMA, DDAH, NO, inflammatory/coagulation markers, endothelial function [brachial and microvascular flow-mediated dilation (FMD)], and cardiac structure and function using comprehensive echocardiography with speckle-tracking strain.<br><br>RESULTS: PASC+ exhibited the highest inflammatory and thrombotic markers, with D-dimer being&#x2009;>&#x2009;3-fold higher than controls, and hs-CRP nearly threefold higher. PASC+ demonstrated lower NOx and substantially higher ADMA than the other two groups, accompanied by only modest DDAH upregulation, suggesting insufficient counter-regulation. Endothelial function was significantly impaired in the PASC+ group compared to the control and PASC- groups, as evidenced by lower brachial and microvascular FMD. PASC+ individuals exhibited worse longitudinal mechanics and higher levels of hs-troponin and NT-proBNP. Ejection fraction was lower in PASC+ compared with Controls and PASC-.<br><br>CONCLUSIONS: These findings identify an imbalance in the ADMA-DDAH-NOx axis that is associated with endothelial dysfunction and cardiac involvement in cardiovascular-symptom PASC, supporting a potentially targetable pathway for risk stratification and therapeutic investigation.},
}
@article {pmid42099508,
year = {2026},
author = {Kawaguchi, M and Sakurada, Y and Tokumasu, K and Otsuka, Y and Nakano, Y and Matsuda, Y and Honda, H and Omura, D and Matsuki, N and Furukawa, M and Higashikage, A and Otsuka, F},
title = {Clinical Utility of SARS-CoV-2 Antibody Titers in the Management of Patients With Long COVID Infected With the Omicron Variant.},
journal = {British journal of biomedical science},
volume = {83},
number = {},
pages = {16255},
pmid = {42099508},
issn = {2474-0896},
mesh = {Humans ; Male ; Female ; *COVID-19/immunology/blood/virology/diagnosis ; Middle Aged ; *SARS-CoV-2/immunology ; Retrospective Studies ; *Antibodies, Viral/blood ; Adult ; Aged ; Spike Glycoprotein, Coronavirus/immunology ; COVID-19 Vaccines/administration &amp; dosage/immunology ; Coronavirus Nucleocapsid Proteins/immunology ; },
abstract = {BACKGROUND: Long COVID (LC) presents persistent symptoms that pose a major clinical challenge. Identification of reliable biomarkers to evaluate LC pathophysiology is needed.<br><br>OBJECTIVES: To investigate whether serum S- and N-antibody titers against SARS-CoV-2 spike and nucleocapsid proteins reflect the clinical features of LC.<br><br>METHODS: This retrospective observational study included patients diagnosed with Omicron variant-related LC who attended a post-COVID-19 outpatient clinic between July 2023 and November 2024 and provided informed consent for antibody testing.<br><br>RESULTS: Among 275 patients (129 men and 146 women), 57 (21%) were unvaccinated. Median S- and N-antibody titers in vaccinated versus unvaccinated patients were 20,963&#xa0;U/mL and 24.8 cut-off index (COI) versus 24&#xa0;U/mL and 44.5 COI, respectively. S-antibody titers were associated with the number of vaccine doses received, whereas N-antibody titers correlated with disease severity during the acute phase of COVID-19 infection, with females having higher titers by multivariable analysis. N-antibody titers in unvaccinated patients with LC were negatively correlated with time interval from infection to clinic visit, with an estimated daily decline of 0.34% in measured N-antibody levels. Patients with LC having memory impairment had low S-antibody titers by multivariable logistic regression analysis, and low S-antibody levels were associated with reduced quality of life (QOL). Additionally, N-antibody titers positively correlated with lymphocyte counts and immunoglobulin levels.<br><br>CONCLUSION: Serum N-antibody titers reflect immune responses to COVID-19, although they are affected by gender differences and interval between infection and evaluation. Lower S-antibody titers were associated with brain fog symptoms and reduced QOL in patients with LC.},
}
@article {pmid42099668,
year = {2026},
author = {McAlpine, LS and Shorer, EF and Chiarella, J and Nelson, A and Veenhuis, R and Azola, A and Lee, A and Pierce, R and Farhadian, S and Rubin, LH and Spudich, SS and , and , },
title = {Vascular inflammation in neuropsychiatric long COVID.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {54},
number = {},
pages = {101247},
pmid = {42099668},
issn = {2666-3546},
abstract = {The role of vascular inflammation in neuropsychiatric Long COVID (LC) is suspected but not well understood. This study evaluated whether vascular inflammation is present in individuals with neuropsychiatric LC and how it relates to cognitive and mental health symptoms. This cross-sectional, case-control study included individuals with acute COVID-19 (AC), neuropsychiatric LC, and recovered controls. Participants were enrolled from the COVID Mind Study and the Yale IMPACT Study (hospitalized), and an independent cohort from the Johns Hopkins University (JHU) Long COVID Study. Fifty individuals with neuropsychiatric LC (new symptoms a median of 368 days post-COVID), 28 with AC, and 29 recovered controls (>3 months post-COVID) were evaluated. All underwent blood sampling and neuropsychiatric testing. The JHU cohort included 114 individuals with late LC (median 1065 days post-COVID illness associated with LC onset) and 31 recovered controls (median 852 days). Fourteen plasma biomarkers of vascular inflammation were measured. ANCOVA was used to compare groups, adjusting for comorbidities. Non-hospitalized participants completed the Global Neuropsychological Assessment, GAD-7, and PHQ-9. LC and recovered groups were demographically similar, while AC participants had higher obesity and hypertension rates. LC participants had elevated circulating biomarkers of endothelial, leukocyte, and platelet adhesion (sL-selectin, ADAMTS13, sP-selectin, sICAM-1) compared to recovered controls. Coagulation markers (D-dimer, fibrinogen) did not differ. Most biomarkers were highest in AC and lower in LC; however, fetuin, sL-selectin, and α-2 macroglobulin were higher in LC than AC. In LC, higher sP-selectin correlated with lower fluency and verbal learning. Lower α1-acid glycoprotein levels were strongly associated with poorer verbal memory, verbal learning, fluency, depression, and anxiety. In the JHU cohort, late LC and recovered controls showed no differences in biomarkers or demographics, suggesting normalization over time. Persistent dysregulation at the intersection of inflammation, platelet adhesion, and endothelial dysfunction is strongly linked to neuropsychiatric Long COVID. Elevated markers of endothelial adhesion in LC suggest distinct pathophysiology from AC. These biomarkers correlate with lower fluency and verbal learning, linking vascular dysfunction to brain function. This study underscores the critical need for longitudinal, within-person investigations to elucidate how vascular inflammation evolves over time.},
}
@article {pmid42099690,
year = {2026},
author = {Phafane, MP and Isabirye, A and Reddy, P},
title = {Predictors of Long COVID-19 Syndrome and Hospital Admissions Among COVID-19-Diagnosed Adult Patients Who Self-Isolated at Home in KwaZulu-Natal Province, South Africa.},
journal = {Nursing research and practice},
volume = {2026},
number = {},
pages = {9317685},
pmid = {42099690},
issn = {2090-1429},
abstract = {Long COVID-19 (LC) syndrome is a complex systemic illness that is currently recognised to have a high morbidity rate and hospitalisations. The study analysed factors linked to LC in adults self-isolated during COVID-19 infection in KwaZulu-Natal Province, South Africa, focusing on two densely populated districts (uMgungundlovu and eThekwini Metro Municipality). We employed a cross-sectional study among individuals aged 18 years and above who self-isolated at home. Demographic data, COVID-19 vaccination status, and post-COVID-19 health symptoms were collected using a standardised questionnaire. The National Health and Nutrition Survey's Physical Functioning Questionnaire was adapted to evaluate health and functional outcomes six months after a COVID-19 diagnosis, addressing both physical and psychosocial symptoms during that timeframe. A modified Poisson regression model was used to determine the predictors of LC and hospitalisation. Of the 280 participants, 46% (n = 130) reported having at least one health-related symptom, while 36% (n = 47) had ≥ five symptoms. Approximately half of the participants (50%, n = 139) had at least one hospital admission following infection due to persistent symptoms. Older age (aIRR 1.5; 95% CI: 1.2-3.2; p = 0.021), reinfection (aIRR 2.0; 95% CI: 1.3-3.0; p = 0.001), having positive household contacts (aIRR 2.1; 95% CI: 1.4-3.2; p < 0.001) and hospitalisation (aIRR 7.7; 95% CI: 3.8-15.6; p < 0.001) increased the risk of developing LC. Post-infection hospitalisation was significantly associated with symptoms such as anxiety (aIRR 1.4; 95% CI: 1.1-1.7; p = 0.009), depression (aIRR 1.9; 95% CI: 1.6-2.3; p < 0.001), sore throat (aIRR 1.5; 95% CI: 1.7-2.0; p = 0.002) and weight loss (aIRR 1.8; 95% CI: 1.4-2.4; p < 0.001). A considerable percentage of participants with post-SARS-CoV-2 infections presented with long-term complications and required medical intervention. Postpandemic healthcare planning and resource allocation need to be considered since increased morbidities associated with LC place a burden on the already inadequately funded healthcare system.},
}
@article {pmid42101066,
year = {2026},
author = {Boufleuer, E and Vieira, TW and Sakamoto, VTM and Anschau, F and Tavares, JP and Filho, FFD and Pai, DD},
title = {Psychological and Cognitive Sequelae of COVID-19: Systematic Review and Meta-Analysis.},
journal = {Journal of psychiatric and mental health nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpm.70139},
pmid = {42101066},
issn = {1365-2850},
support = {312850/2025-5//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
abstract = {INTRODUCTION: COVID-19 pandemic has exacerbated global mental health problems with the development of persistent symptoms.<br><br>AIM: To conduct a prevalence meta-analysis of persistent psychological and cognitive sequelae of COVID-19 based on cohort studies.<br><br>METHOD: This study followed PRISMA. Cohort studies that followed individuals for at least 12&#x2009;weeks post-COVID-19 were included and pediatric studies were excluded. The databases Embase, Lilacs/BVS, PubMed, SciELO and Scopus were searched in November 2023. Meta-analyses were performed with subgroup analyses conducted. Results were presented with forest plot graphs and tables. Risk of bias and methodological quality were assessed using Eggers's Test and the Newcastle-Ottawa Scale.<br><br>RESULTS: 2,456 studies were identified and screened. Forty-seven articles were included in the systematic review, and 46 in the meta-analysis (192,158 participants). The most prevalent psychological outcome was anxiety (0.17; 95% CI 0.11-0.27, 19 studies), followed by cognitive impairments (0.15; 95% CI 0.11-0.20, 35 studies), sleep disturbances (0.14; 95% CI 0.09-0.19, 33 studies) and depression (0.11; 95% CI 0.06-0.19, 16 studies).<br><br>DISCUSSION: The mental health consequences of COVID-19 highlight the need for long-term monitoring and represent a significant public health challenge. The limitation is the heterogeneity among the studies.<br><br>These findings represent a public health issue emphasizing the need for public policies and support strategies to mitigate consequences.<br><br>CONCLUSION: Although high prevalence rates were identified, the prediction intervals were wide and heterogeneity remained high-common characteristics of studies conducted during the pandemic.<br><br>REGISTRATION: Registered in the international Prospective Register of Ongoing Systematic Reviews (PROSPERO) under number CRD42023460632, on&#xa0;September 5, 2023.},
}
@article {pmid42101068,
year = {2026},
author = {Lin, CH and Lai, CY and Chang, CY and Chao, TC and Song, CY and Chang, CC and Chang, WY and Huang, CY and Jhuang, JW and Chiang, SL},
title = {Factors associated with low anaerobic threshold and its impact on sleep quality and health-related quality of life in individuals with long COVID.},
journal = {PM &amp; R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70133},
pmid = {42101068},
issn = {1934-1563},
support = {TSGH-E-113279//Tri-Service General Hospital/ ; TSGH-E-114273//Tri-Service General Hospital/ ; TSGH-E-115276//Tri-Service General Hospital/ ; MND-MAB-D-114120//Medical Affairs Bureau, Ministry of National Defense/ ; MND-MAB-D-115223//Medical Affairs Bureau, Ministry of National Defense/ ; 114-2221-E-016-002-MY2//National Science and Technology Council/ ; },
abstract = {INTRODUCTION: Anaerobic threshold (AT), a crucial indicator of submaximal exercise capacity and cardiorespiratory function, has been reported to be impaired in individuals with long COVID. However, the predictors of reduced AT during exercise in this population and its impacts on patient-reported outcomes, including sleep quality and health-related quality of life (HRQL), remain unknown. This study aims to identify factors associated with low AT and examine its relationship with patient-reported outcomes.<br><br>OBJECTIVE: To investigate the predictors of low AT and compare patient-reported outcomes (sleep quality and HRQL) between individuals with normal and low AT among those with long COVID.<br><br>DESIGN: Cross-sectional study.<br><br>SETTING: Post-COVID integrated outpatient clinic at a medical center in northern Taiwan.<br><br>PATIENTS (OR PARTICIPANTS): Eligible patients aged 20-80&#x2009;years with long COVID were recruited.<br><br>INTERVENTIONS: Not applicable.<br><br>MAIN OUTCOME MEASURE(S): AT, peak oxygen consumption (peak VO2), and patient-reported outcomes, including sleep quality and HRQL, assessed using the Taiwanese version of the World Health Organization Quality of Life-BREF and Pittsburgh Sleep Quality Index.<br><br>RESULTS: Factors associated with low AT included younger age (odds ratio [OR]&#x2009;=&#x2009;0.904, 95% confidence interval [CI]: 0.867-0.942, p&#x2009;<&#x2009;.001) and lower peak VO2 (OR&#x2009;=&#x2009;0.737, 95% CI: 0.659-0.842, p&#x2009;<&#x2009;.001). Participants with low AT exhibited impaired patient-reported outcomes including poorer sleep quality (p&#x2009;=&#x2009;.008), and lower HRQL scores across all domains, as compared to those with normal AT. After adjustment for significant covariates, only the psychological domain of HRQL remained statistically significant (adjusted p&#x2009;=&#x2009;.035).<br><br>CONCLUSIONS: Low AT in individuals with long COVID was associated with younger age and lower peak VO2. Its independent impact on sleep quality and HRQL appears limited, suggesting that patient-reported outcomes may be influenced by multiple interacting factors and warrant further investigation.},
}
@article {pmid42101592,
year = {2026},
author = {Knowles, LM and O'Loughlin, KM and Gentile, NL and Herring, TE},
title = {Managing Anxiety and Depression Symptoms in Long COVID.},
journal = {American family physician},
volume = {113},
number = {4},
pages = {315-317},
pmid = {42101592},
issn = {1532-0650},
}
@article {pmid42102594,
year = {2026},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Effect of a third COVID-19 vaccine dose on the incidence of Long COVID among adults who completed a primary vaccine series: a target trial emulation in a community-based cohort.},
journal = {Vaccine},
volume = {84},
number = {},
pages = {128666},
doi = {10.1016/j.vaccine.2026.128666},
pmid = {42102594},
issn = {1873-2518},
abstract = {BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving ≥1 third dose versus completing only a primary series on 6- and 12-month long COVID incidence using a target-trial emulation in a U.S. community cohort.<br><br>METHODS: We analyzed the CHASING COVID Cohort, a prospective, community-based study of U.S. adults. Eligible participants were&#xa0;&#x2265;&#xa0;18&#xa0;years, had completed a two-dose primary series, had no prior long COVID, and had no SARS-CoV-2 infection in the 3&#xa0;months before time zero. Strategies compared were: receive a third dose at time zero vs. not receive a third dose during follow-up. Long COVID was defined as &#x2265;1 new symptom at or beyond 3&#xa0;months post-infection with concurrent activity limitation, both absent in the prior year. Follow-up was 6 and 12&#xa0;months. We used a per-protocol analog: participants were artificially censored upon deviating from their assigned strategy or lost-to-follow-up, with inverse-probability weights to address selection due to censoring and time-varying confounding. We fit weighted pooled logistic models to estimate weighted incidence, differences, and ratios at each horizon.<br><br>RESULTS: Across 16 sequential trials (18,930 person-trials; 4044 unique individuals), 3321 person-trials received a third dose at time zero and 15,609 did not. At 6&#xa0;months, weighted long COVID incidence was 0.9% (95% CI, 0.5%, 1.3%) with a third dose vs. 1.0% (0.8%, 1.1%) without (risk difference (RD), -0.1%; 95% CI, -0.5%, 0.4%; risk ratio (RR), 0.93; 95% CI, 0.54, 1.44). At 12&#xa0;months, incidence was 4.9% (4.1%, 5.9%) with a third dose vs. 4.5% (4.1%, 4.8%) without (RD, 0.4%; 95% CI, -0.5%, 1.4%; RR, 1.09; 95% CI, 0.90, 1.33).<br><br>CONCLUSION: In this community-based target-trial emulation, receiving a third COVID-19 vaccine dose did not meaningfully reduce 6- or 12-month long COVID incidence compared with completing only a primary series.},
}
@article {pmid42103380,
year = {2026},
author = {Manuel, K and Davis, A and Little, K and Peng, F and Gwilt, I and Laver, K and Adey-Wakeling, Z and Seaforth, C and Crotty, M},
title = {Model of care to promote recovery in older people with long COVID: findings from interviews and a co-design workshop.},
journal = {BMJ open},
volume = {16},
number = {5},
pages = {e109911},
doi = {10.1136/bmjopen-2025-109911},
pmid = {42103380},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/therapy/psychology ; Aged ; South Australia ; Female ; Male ; SARS-CoV-2 ; Interviews as Topic ; Aged, 80 and over ; Chronic Disease ; Qualitative Research ; Patient-Centered Care ; },
abstract = {OBJECTIVES: This study aimed to co-design a tailored model of care for older people with long COVID.<br><br>DESIGN: Using a human-centred design approach, semistructured interviews were conducted with patients and health professionals from a long COVID service to explore their experiences. Insights were further developed during a co-design workshop involving patients, health professionals and community members who identified as older people and who had experience with chronic illness. Key themes were identified and used to map an ideal patient journey and inform the final model of care.<br><br>SETTING: Long COVID outpatient service in a tertiary hospital in Adelaide, South Australia.<br><br>PARTICIPANTS: Four patients and four health professionals participated in the interviews. The workshop included four patients, five health professionals and seven community members.<br><br>RESULTS: The co-design process identified challenges experienced by people with long COVID, including lack of validation, delayed multidisciplinary care, mental health deterioration and difficulties navigating the healthcare system. These challenges were described as having particular relevance for older adults. In response, a model of care was developed focused on comprehensive assessment, coordinated multidisciplinary care, education for self-management, mental health support and opportunities for research participation.<br><br>CONCLUSIONS: A comprehensive and adaptable model of care is needed to address the complex and multifaceted nature of long COVID. This human-centred design approach ensured the model was grounded in lived experience, clinically informed and aligned with patient priorities. While not unique to older adults, the findings highlight areas that may require particular attention in this population, including care coordination, validation and support for comorbidities and social vulnerabilities. While developed in a single tertiary service, these principles may inform the design of services for similar populations in other healthcare settings.},
}
@article {pmid42094075,
year = {2026},
author = {Chen, Z and Zhang, Z and Huang, Y and Du, Z and Chen, R and Chen, N and Liu, T and Cheng, Y and Wang, H and Xiong, H and Song, L and Ye, Y and Lu, Y and Lv, Z and Cao, T and Li, Y and Zhu, B and Zou, X and Lu, J and Fang, S and Cowling, BJ},
title = {Epidemiological Trends of COVID-19 Infection and Symptom Incidence in China Following the Adjustment of Zero-COVID Policy: A Prospective, Community-Based Cohort Study.},
journal = {Transboundary and emerging diseases},
volume = {2026},
number = {},
pages = {5590977},
pmid = {42094075},
issn = {1865-1682},
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; China/epidemiology ; Incidence ; Middle Aged ; Male ; Female ; Prospective Studies ; Adult ; Aged ; SARS-CoV-2 ; Young Adult ; Adolescent ; COVID-19 Vaccines/administration &amp; dosage ; },
abstract = {This study tracked the postadjustment infection rates and symptom trends within community settings. Conducted from May 2023 to May 2024 across four districts in Shenzhen, involving 3246 participants, over 80% had received at least one vaccine dose. Postpolicy adjustment witnessed three significant infection surges. Among the cohort, 63.7% reported only one Coronavirus disease 2019 (COVID-19) infection, 30.3% two infections, and 1.7% three infections, with 4.3% remaining uninfected throughout the follow-up. Older adults and those with lower IgG levels had increased reinfection risk. Notably, 3.8% (95% CI: 3.1-4.6) reported long COVID, with higher susceptibility in those with underlying conditions (adjusted odds ratio [AOR] = 3.73, 95% CI: 2.20-6.34) and reduced incidence among fully vaccinated individuals (AOR = 0.57, 95% CI: 0.36-0.90). The policy change led to widespread exposure, shifting from first infections to reinfections. These insights underscore the need for ongoing research to inform future pandemic responses.},
}
@article {pmid42094409,
year = {2026},
author = {Montague, Z and Grover, RM and Baumgartner, A and Trofimov, A and Hadlock, J and Nourmohammad, A},
title = {T-cell repertoire response in individuals with post-acute sequelae of COVID-19.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.27.721205},
pmid = {42094409},
issn = {2692-8205},
abstract = {T-cells are central to SARS-CoV-2 clearance and immunological memory, yet their contribution to the persistence of post-acute sequelae of COVID-19 (PASC) remains poorly understood. The immunological features that distinguish individuals who develop PASC from those who recover fully are unresolved, in part due to the phenotypic heterogeneity of the condition and the likely multiplicity of its underlying mechanisms. Here, we profiled longitudinal bulk TCR β repertoires from 120 individuals in the INCOV cohort-71 with PASC and 49 without-sampled at two to three time points spanning the acute and post-acute phases of infection. Using robust statistical modeling of repertoire composition and clonal dynamics, we found that global statistics such as V, J gene usage and CDR3 length do not differ between groups, but that locally enriched sequence motifs and differentially dynamic clones reveal distinct T-cell signatures associated with PASC status. Clones contracting following the peak of the acute response were significantly enriched for SARS-CoV-2 specificity in both groups. Interestingly, Influenza A-specific TCRs were disproportionately enriched among contracting clones in PASC [+] repertoires, implicating viral co-infection as a potential contributor to early disease severity and, possibly, PASC pathogenesis. Rare public TCR clones were markedly enriched for SARS-CoV-2 specificity, with PASC [+] individuals harboring a modestly but significantly higher proportion than PASC [-] individuals. Together, we identified over 1,000 candidate TCR β receptors potentially discriminating PASC [+] from PASC [-] immune responses, opening a path toward the identification of disease-relevant T-cell specificities and the development of T-cell-based immunological biomarkers for long COVID.},
}
@article {pmid42088012,
year = {2026},
author = {Kim, TH and Yoon, J and Kang, BK and Kang, JW and Jin, YH and Kwon, CY and Kwon, S},
title = {Herbal medicine (Kyungok-go) for fatigue in Long COVID patients: A prospective multicenter pilot study.},
journal = {Integrative medicine research},
volume = {15},
number = {3Part A},
pages = {101336},
pmid = {42088012},
issn = {2213-4220},
abstract = {BACKGROUND: Long COVID, defined as symptoms persisting beyond 12 weeks after acute SARS-CoV-2 infection, has emerged as a significant global health concern. Fatigue is one of its most common and disabling symptoms, yet robust clinical evidence for effective treatments remains limited.<br><br>METHODS: We conducted a multicenter, prospective, single-arm pilot study to evaluate the feasibility and potential effectiveness of Kyungok-go (Qiong-Yu-Gao), a traditional Korean herbal medicine, in individuals with Long COVID-related fatigue. A total of 100 participants experiencing fatigue for at least 12 weeks following a COVID-19 diagnosis received Kyungok-go (22.5 g twice daily) for 12 weeks. The primary outcome was the change in Fatigue Severity Scale (FSS) scores. Secondary outcomes included fatigue severity assessed by a Visual Analog Scale (VAS) and the Chalder Fatigue Scale (ChFS), along with sleep quality, depressive symptoms, cognitive and physical function, and quality of life. Feasibility was assessed through recruitment rate, treatment adherence, and dropout rates.<br><br>RESULTS: Ninety-four participants completed the study. FSS scores improved significantly (mean difference (MD) -2.1; 95% CI, -2.4, -1.9), accompanied by significant reductions in fatigue severity on the VAS (MD -35.6; 95% CI, -39.7, -31.4) and ChFS total score (MD -29.1; 95% CI, -32.3, -25.9). Sleep quality (MD -4.0; 95% CI, -4.8, -3.2), depressive symptoms (MD -8.1; 95% CI, -9.6, -6.7), and overall quality of life (EQ-5D-5L, MD 0.1; 95% CI, -0.1, 0.1) also showed improvements. Cognitive (MD 0.9; 95% CI, 0.2, 1.5) and physical function (MD 0.2; 95% CI, 0.0, 0.3) showed modest or limited changes. Medication adherence exceeded 97%, and no serious treatment-related adverse reactions were observed.<br><br>CONCLUSION: Kyungok-go was well-tolerated and showed promising effects in alleviating fatigue among patients with Long COVID. These findings support its feasibility and potential as a therapeutic option, warranting further evaluation in randomized controlled trials.<br><br>TRIAL REGISTRATION: CRIS, KCT0009410 (https://cris.nih.go.kr/).},
}
@article {pmid42088257,
year = {2026},
author = {Jia, X and Wang, J and Cui, X and Li, T and Tian, Y and Lu, R and Tian, Y and Shen, X and Dang, S and Wang, W},
title = {Trends in long COVID among US adults, 2022-2024.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1809635},
pmid = {42088257},
issn = {2296-2565},
mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/epidemiology ; United States/epidemiology ; Adult ; Cross-Sectional Studies ; Prevalence ; Socioeconomic Factors ; Aged ; SARS-CoV-2 ; Health Surveys ; Activities of Daily Living ; Young Adult ; Adolescent ; },
abstract = {IMPORTANCE: Long COVID poses a significant public health challenge. However, population-level trends and associated factors in the general US population during the post-pandemic era are not fully characterized.<br><br>OBJECTIVE: To analyze trends in long COVID prevalence among US adults from 2022 to 2024, identify associated demographic and socioeconomic factors, and assess its impact on daily activities.<br><br>We analyzed data from three cycles (2022-2024) of the National Health Interview Survey, a repeated cross-sectional, nationally representative survey. COVID-19 infection, long COVID, and daily activity limitation were determined through participant self-report. Daily activity limitation was assessed in 2023-2024. Multivariable Poisson regression identified factors associated with: (1) long COVID history and (2) significant activity limitation among those with current symptoms. All analyses incorporated survey weights to produce nationally representative estimates. Data analysis was conducted in October 2025.<br><br>RESULTS: The study included 88,731 adults (median age 47&#x202f;years; 51.4% female and 48.6% male; 61.7% non-Hispanic White, 17.6% Hispanic, 11.8% non-Hispanic Black, and 8.9% non-Hispanic other). In the overall population, the prevalence of ever long COVID increased from 7.0% (95% CI, 6.6-7.3%) in 2022 to 8.4% (95% CI, 8.0-8.8%) in 2023, plateauing at 8.3% (95% CI, 7.9-8.7%) in 2024, while for current long COVID the prevalence remained stable (3.4% [95% CI, 3.1-3.6%] in 2022, 3.6% [95% CI, 3.3-3.9%] in 2023, and 3.3 [95% CI, 3.1-3.6%] in 2024). Among adults with prior COVID-19 infection, prevalence of both ever and current long COVID declined significantly, from 17.7 to 13.7% and from 8.6 to 5.5%, respectively. Long COVID was more common among women, adults in middle age (35-64&#x202f;years), Hispanic or non-Hispanic White individuals, those who were widowed/separated/divorced, people with lower educational attainment, and individuals with incomes below the federal poverty threshold. Among those with current long COVID, 19.8% reported significant activity limitation, and this limitation was more common among older adults and individuals with lower incomes.<br><br>CONCLUSIONS AND RELEVANCE: From 2022 to 2024, long COVID continued to impose a substantial public health burden, with clear demographic and socioeconomic disparities. These findings underscore the necessity for continued surveillance and targeted support for high-risk groups.},
}
@article {pmid42088258,
year = {2026},
author = {Huang, H and Chen, S and Fang, Z and Ma, Y and Xu, Y and Dong, G},
title = {The "two-hit" storm: a hyper-inflammatory endotype in pediatric long COVID and its role in the severity of secondary bacterial pneumonia-a mechanistic review and clinical implications.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1782871},
pmid = {42088258},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/immunology/complications ; Child ; SARS-CoV-2 ; *Pneumonia, Bacterial/immunology ; *Inflammation/immunology ; Severity of Illness Index ; Pneumonia, Mycoplasma/immunology ; },
abstract = {Following the COVID-19 pandemic, the clinical patterns of pediatric respiratory infections have undergone significant changes, with increasing attention on the immunological imprint left by Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID. A perplexing clinical phenomenon has been observed: some children with a history of Long COVID exhibit a disproportionately severe inflammatory response and extensive lung injury when encountering common community-acquired pneumonia, such as that caused by Mycoplasma pneumoniae or Streptococcus pneumoniae, inconsistent with their pathogen load. This review aims to dissect this phenomenon and proposes the "Immune Priming and Two-Hit" model as its core pathophysiological framework. This model posits that the Long COVID state constitutes the "first hit," establishing a "primed" or "hyper-reactive" immune baseline through viral persistence, trained immunity-induced monocyte reprogramming, and sustained endothelial dysfunction. Upon the "second hit" of a bacterial infection, this primed immune system triggers a dysregulated, synergistically amplified inflammatory cascade. The mechanisms involve the exponential release of cytokines such as Interleukin-6 (IL-6), IL-1β, and Tumor Necrosis Factor-α (TNF-α), inflammation-mediated immunothrombosis, and excessive activation of Neutrophil Extracellular Trap formation (NETosis), ultimately leading to severe outcomes like Acute Respiratory Distress Syndrome (ARDS) and necrotizing pneumonia. Consequently, identifying and defining this "Hyper-inflammatory endotype" is of critical clinical importance. We define it as an "endotype" to emphasize the distinct, host-determined pathophysiological mechanisms underlying it, rather than merely a collection of clinical manifestations. By monitoring biomarkers such as ferritin, D-dimer, lactate dehydrogenase (LDH), and lymphocyte counts, clinicians may be able to perform early risk stratification of these children. This approach not only facilitates a shift in therapeutic strategy from purely antimicrobial therapy to "host-directed therapy"-emphasizing the necessity of early, adequate corticosteroid use and consideration of anticoagulation-but also provides a new theoretical basis and intervention window for preventing long-term sequelae such as pulmonary fibrosis.},
}
@article {pmid42090436,
year = {2026},
author = {Chu, L and Hollar, TL and Klimas, N and Bertolli, J and Tamariz, AL and Lajevardi, A and Pavlov, I and Palacio, A},
title = {Facilitators of and barriers to participation in Long COVID research: A qualitative analysis.},
journal = {PloS one},
volume = {21},
number = {5},
pages = {e0346007},
doi = {10.1371/journal.pone.0346007},
pmid = {42090436},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology/virology ; Female ; Male ; Middle Aged ; Adult ; SARS-CoV-2/isolation &amp; purification ; Qualitative Research ; Motivation ; *Patient Selection ; Aged ; },
abstract = {BACKGROUND: Meeting recruitment targets in an expeditious manner is essential to the successful completion of any research project. However, despite the high prevalence and debilitating nature of Long COVID (LC), recruitment of participants into some LC studies has been challenging.<br><br>OBJECTIVE: We aimed to a) identify factors influencing participation in LC research among individuals who were infected by SARS-CoV-2 but had declined participation in a LC study and b) to compare these factors to those previously recognized.<br><br>METHODS: Using a semi-structured guide, we interviewed thirteen people about their thoughts, experiences, and attitudes concerning participation in LC research. We imported interview transcripts into Nvivo 14 and analyzed them using thematic analysis. For coding, we used Charmaz's coding scheme of open and focused coding within an application of the constant comparative method. Basic descriptive statistics were also deployed to supplement our qualitative analysis.<br><br>RESULTS: Fifteen factors describe the facilitators and barriers mentioned by participants. The top three facilitators were Personal and social motivation, Incentives, and Familiarity and credibility of institutions involved with COVID-19; the top three barriers were Invasiveness, Social and political context, and Lack of time. Skepticism and infringement on participants' daily lives served as major obstacles to participation while trust, personal factors, and administrative factors encouraged participation. The facilitators and barriers identified are similar to those recognized previously except that in the politically charged atmosphere surrounding the COVID-19 pandemic, trust was especially vital.<br><br>CONCLUSIONS: Many factors affect people's decisions to participate in LC research but only some are modifiable by researchers. Building trust, offering incentives participants value, and removing logistical barriers may improve recruitment rates.},
}
@article {pmid42086409,
year = {2026},
author = {Elahi, S},
title = {Erythroid-hormonal axis in long COVID.},
journal = {Trends in molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molmed.2026.04.006},
pmid = {42086409},
issn = {1471-499X},
abstract = {Long COVID may reflect a failure of coordinated physiological recovery rather than persistent infection. Emerging evidence identifies inflammation-driven disruption of erythropoiesis and hormonal balance as central mechanisms linking immune dysregulation, metabolic stress, and persistent symptoms. This framework positions erythroid-endocrine pathways as key determinants of recovery and promising therapeutic targets.},
}
@article {pmid42086796,
year = {2026},
author = {Pietranis, KA and Kuryliszyn-Moskal, A and Moskal-Jasińska, D and Wojciuk, M and Ciołkiewicz, M and Kaniewska, K},
title = {Effectiveness of comprehensive rehabilitation for functional recovery and symptom reduction in long COVID: results from a six‑month randomised controlled trial.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-51787-2},
pmid = {42086796},
issn = {2045-2322},
support = {SUB/1/DN/22/001/3309//Uniwersytet Medyczny w Bialymstoku/ ; },
abstract = {This study provides a comprehensive evaluation of the long-term clinical outcomes of an original rehabilitation programme for patients with long-COVID, highlighting the sustained therapeutic benefits over a six-month period. Seventy‑five patients with long‑COVID symptoms completed a six‑week programme comprising three weekly outpatient sessions. Participants were randomly assigned to two groups following an identical comprehensive protocol, incorporating aerobic training, respiratory exercises, strength and general fitness training, stretching, and respiratory resistance training with a respiratory muscle trainer, with the control group receiving placebo IMT. The study evaluated the programme's effectiveness by assessing respiratory function (spirometry, muscle strength, chest expansion, and DTF), voice and speech quality, and symptom persistence. The six-month follow-up analysis demonstrated statistically significant retention of improvements in functional and qualitative parameters compared with post-rehabilitation values, with further gains relative to baseline. Our findings indicate that the multi‑component rehabilitation programme is broadly beneficial, with the greatest functional gains in patients with lower baseline capacity, while offering equitable, low‑cost support across age and sex groups and enabling targeted allocation of intensive monitoring to those with the highest potential for clinically meaningful improvement. The study is the first comprehensive analysis of the relationship between long‑COVID and voice and speech‑related disabilities, while also validating the clinical efficacy of the intervention.Clinical trials registration: NCT05449379; 08/07/2022.},
}
@article {pmid42086912,
year = {2026},
author = {Guardo, C and Xinmeng, Z and Gangireddy, S and Chao, Y and Kerchberger, VE and Dickson, AL and Pfaff, ER and Master, H and Yi, X and Basford, M and Chute, CG and Tran, NK and Mancuso, S and Syed, TA and Zhongming, Z and QiPing, F and Haendel, M and Lunt, C and Harris, PA and Lang, L and Ginsburg, GS and Denny, JC and Roden, DM and Wei-Qi, W},
title = {Multi-scale data improves performance of machine learning model for long COVID identification.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01621-7},
pmid = {42086912},
issn = {2730-664X},
support = {U01HG011181//U.S. Department of Health &amp; Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; R01HL171809//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01AG084550//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01 GM139891/GM/NIGMS NIH HHS/United States ; },
abstract = {BACKGROUND: Long COVID affects a substantial proportion of the over 778 million individuals infected with SARS-CoV-2, yet predictive models remain limited in scope. While existing efforts, such as the National COVID Cohort Collaborative (N3C), have leveraged electronic health record (EHR) data for risk prediction and identification, accumulating evidence points to additional contributions from social, behavioral, and genetic factors.<br><br>METHODS: Using a diverse cohort of SARS-CoV-2-infected individuals (n&#x2009;>&#x2009;17,200) from the NIH All of Us Research Program, we investigated whether integrating EHR data with survey-based and genomic information improves model performance.<br><br>RESULTS: Our multi-scale approach outperforms EHR-only model's area under the receiver operating curve 0.736 (95% CI: 0.730, 0.741), achieving an area of 0.748 (0.741,0.755). Among the top predictors, active-duty service status, and self-reported fatigue are the most informative survey features.<br><br>CONCLUSIONS: These findings highlight the importance of incorporating multi-scale data to improve risk stratification and inform personalized interventions for long COVID. However the relative increase in accuracy is modest, and the cost of collecting genetic and survey data should be considered before implementation.},
}
@article {pmid42087199,
year = {2026},
author = {Yoon, GY and Chung, YC and Choi, JH and Ha, Y and Seo, SY and Ku, KB and Kim, DY and Hwang, WY and Jeong, GU and Ahn, DG and Kim, KD and Rhee, JK and Shin, WH and Kwon, YC},
title = {SARS-CoV-2 infection is associated with hypothalamic orexin suppression and persistent cortical NeuN attenuation.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03842-y},
pmid = {42087199},
issn = {1742-2094},
support = {RS-2025-25441317//Ministry of Education, South Korea/ ; RS-2021-NR061451//Ministry of Science and ICT, South Korea/ ; KK-2505-01//Korea Institute of Toxicology, South Korea/ ; KK2633-20//Korea Research Institute of Chemical Technology, South Korea/ ; RS-2023-00208568//Ministry of Education, Science and Technology/ ; },
abstract = {Long COVID frequently presents with persistent neurological symptoms, including cognitive impairment, fatigue, and sleep disturbances; however, its underlying mechanisms remain unclear. Here, we show that SARS-CoV-2 infection induces lasting cortical neuronal injury and hypothalamic orexin (hypocretin) dysfunction in vivo. In K18-hACE2 and wild-type BALB/c mice, viral RNA persisted in the brain and coincided with focal loss of Neuronal Nuclei (NeuN)-positive cortical neurons beyond acute infection. SARS-CoV-2, but not the influenza A virus, triggered rapid and sustained suppression of hypothalamic orexin expression, defining a virus-specific neuropathological signature. Considering the downregulation of orexin and focal cortical NeuN attenuation, we found that exogenous orexin-A/B supplementation increased NeuN abundance in vitro and in vivo under the tested conditions. Overall, these findings identify the orexin system as a candidate neural vulnerability to SARS-CoV-2 and suggest that orexinergic dysfunction may contribute to the neurological manifestations of Long COVID.},
}
@article {pmid42074658,
year = {2026},
author = {Le Breton, C and Klopfenstein, T and Zayet, S},
title = {Current Difficulties for General Practitioners in the Diagnosis and Management of Long COVID Patients: A Cross-Sectional Study Assessing an Online Questionnaire.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082855},
pmid = {42074658},
issn = {2077-0383},
abstract = {Background: Long COVID presents a novel and emerging public health challenge. As the first point of contact, general practitioners (GPs) play a key role in diagnosing and coordinating the care of patients presenting with post-acute sequelae of COVID-19 (PASC), despite a lack of experience. This study aimed to identify the main difficulties encountered by GPs in Franche-Comté, France, in managing adult outpatients with long COVID. Methods: We conducted a cross-sectional survey using an anonymous online questionnaire, which contained 21 questions and was distributed to GPs in Franche-Comté, France. The survey assessed definition, diagnostic and therapeutic challenges in managing long COVID. Results: Among the 410 questionnaires distributed, 90 general practitioners (GPs) responded (response rate: 21.9%). The mean age of participants was 34 ± 10 years, and 64.4% were women (n = 58). Regarding knowledge of long COVID, three participants (3.3%) did not recognize it as a distinct clinical entity, while more than half (58.9%, n = 53) reported insufficient knowledge. The main challenges identified were therapeutic management (76.7%, n = 69) and diagnosis (75.6%, n = 68). Only 4.5% of respondents (n = 4) reported no difficulty in defining post-acute sequelae of SARS-CoV-2 infection (PASC). The most frequently reported diagnostic difficulty was distinguishing long COVID from differential diagnoses (93.3%, n = 83/89), particularly fibromyalgia (94.3%, n = 83/88). Only 37.1% of participants (n = 33/89) reported actively following up patients with PASC. During initial management, the main challenge was the difficulty in objectively assessing patients' complaints using available diagnostic tools (80.7%, n = 67/83). Additionally, a large majority of GPs reported difficulties in addressing patients' questions (86.7%, n = 72/83) and managing associated anxiety disorders (75.9%, n = 63/83). Conclusions: These findings highlight the immediate need to enhance GP training in Franche-Comté, France, in dealing with long COVID. Improvements such as harmonizing long COVID definitions, testing diagnoses, and strengthening interdisciplinary coordination are essential to provide coherent and patient-centered care for this disease.},
}
@article {pmid42074690,
year = {2026},
author = {Lucaciu, FC and Wellmann, N and Mihai, AM and Sima, A and Rosca, O and Suba, MI and Tarau, A and Bosoanca, A and Marc, M},
title = {Post-COVID Respiratory Sequelae in COPD: Mucus Plugging, Infectious Complications, and Risk-Stratified Follow-Up.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082890},
pmid = {42074690},
issn = {2077-0383},
abstract = {Context/Objectives: In patients with COPD (chronic obstructive pulmonary disease), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection represents an overlap of viral injury on a lung already affected by pathological mucus, altered mucociliary clearance, chronic inflammation, and impaired antiviral immunity. Methods: A focused narrative review (2020-2025) was conducted using clinical, experimental, and consensus evidence. The evidence was synthesized qualitatively, with priority given to cohort studies, meta-analyses, and mechanism-focused studies with clinical relevance. Results: Mucus obstruction ("mucus plugs") is frequent in COPD (41-67%) and is associated with unfavorable outcomes. COPD also increases the risk of post-COVID respiratory sequelae. Bacterial coinfection at presentation is uncommon (3-5%), whereas secondary bacterial infections are more frequent (14-18%), especially in severe disease requiring intensive care, where VA-LRTI/VAP (ventilator-associated lower respiratory tract infection/ventilator-associated pneumonia) become predominant. Sepsis, whether viral or mixed, reflects disease severity and may contribute to functional decline and susceptibility to reinfections; however, the concept of a post-acute "sepsis legacy" in COPD after COVID-19 should currently be regarded as a clinically plausible but still emerging hypothesis rather than an established COPD-specific outcome. During recovery, acute exacerbation risk rises to 5.6% versus 3.9%, peaking in the first 30 days after severe disease (aHR ≈ 8.14). Persistent dyspnea and reduced DLCO (diffusing capacity for carbon monoxide) suggest ARDS-related injury, tissue remodeling, and microvascular dysfunction. Conclusions: In COPD, post-COVID respiratory sequelae result from the interaction of mucus, immunity, and infectious/sepsis-related complications. The first post-discharge month is a critical period requiring careful risk stratification and targeted follow-up.},
}
@article {pmid42074919,
year = {2026},
author = {Avram, CA and Craciun, ML and Pah, AM and Iurciuc, S and Crisan, S and Vacarescu, C and Cotet, I and Virzob, CRB and Surducan, DA and Avram, C},
title = {Pulmonary Embolism in Hospitalized COVID-19 Patients: Incidence, Clinical Predictors, and Short-Term Outcomes.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15083117},
pmid = {42074919},
issn = {2077-0383},
support = {Victor Babe&#x219; University of Medicine and Pharmacy Timi&#x219;oara//Victor Babe&#x219; University of Medicine and Pharmacy Timi&#x219;oara/ ; },
abstract = {Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1-7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4-10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies).},
}
@article {pmid42075130,
year = {2026},
author = {Bačić, A and Gmizić, T and Branković, M and Rajilić-Stojanović, M},
title = {Multi-Strain Probiotic Intervention Modestly Modulates Microbial Composition and Inflammatory Profile in Individuals with Long COVID.},
journal = {Microorganisms},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/microorganisms14040734},
pmid = {42075130},
issn = {2076-2607},
support = {No. 451-03-34/2026-03/ 200135//Ministry of Education, Science and Technological Development of the Republic of Serbia/ ; },
abstract = {Probiotics are widely used to support host health by modulating microbial communities and immune-metabolic homeostasis. Such interventions may be particularly relevant in long COVID syndrome, a condition characterized by persistent symptoms, low-grade inflammation, and microbiota alterations following SARS-CoV-2 infection. This study investigated the effects of a multi-strain probiotic on gut microbiota composition and predicted functional potential and biochemical parameters in individuals with long COVID and convalescent participants. Healthy individuals were included as reference controls. In an interventional study, 34 participants received a 12-week probiotic formulation containing Saccharomyces boulardii, Lacticaseibacillus rhamnosus GG, and two Lactiplantibacillus plantarum strains, while 40 served as non-supplemented controls. Fecal microbiota, assessed using 16S rRNA sequencing, and biochemical markers were measured at baseline and post-intervention. Probiotic supplementation induced selective compositional changes without significantly altering overall microbial diversity. Effects were more pronounced in long COVID participants and included enrichment of bacteria associated with metabolic and immune regulation, including Adlercreutzia, Coprococcus, and Eubacterium. Functional prediction analysis identified a probiotic-responsive signature in long-COVID-affected individuals, characterized by enrichment of pathways related to energy metabolism and redox balance. These microbial changes were accompanied by a consistent trend toward reduced inflammatory and hepatic markers. Overall, probiotic intervention demonstrated microbiota-status-dependent potential in long COVID recovery.},
}
@article {pmid42076806,
year = {2026},
author = {Foran, AM and Jetten, J and Muldoon, OT},
title = {Health benefit or burden? Unpacking the dual effects of religious group membership on long COVID prevalence and severity.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053261445238},
doi = {10.1177/13591053261445238},
pmid = {42076806},
issn = {1461-7277},
abstract = {While religious group membership is often linked to positive health outcomes, it can also influence engagement with health advice in ways that present challenges. The role of religious group membership in long COVID prevalence and severity therefore warrants closer examination. This study used cross-sectional data from Round 11 of the European Social Survey (N = 25,124) across 24 countries. Multilevel multinomial logistic mediation models tested whether the association between religious group membership and long COVID was mediated by two divergent pathways: religious attendance (enactment) and religiosity (significance of beliefs). Results showed that membership was indirectly associated with a lower likelihood of reporting long COVID symptoms via more frequent attendance at religious services. By contrast, greater religiosity was associated with a higher likelihood of reporting persistent symptoms. These findings suggest that the health advantages of religious group membership may lie in opportunities for social connexion.},
}
@article {pmid42076812,
year = {2026},
author = {Belton, S and Goss, H and Whyte, E and McCaffrey, N and Gibney, S and Sheridan, K},
title = {'I Want Everyone to Have It, and Everyone to Be on It': A Feasibility Study of the Transforming Long Covid Intervention.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {3},
pages = {e70681},
doi = {10.1111/hex.70681},
pmid = {42076812},
issn = {1369-7625},
mesh = {Humans ; Feasibility Studies ; *COVID-19/complications/therapy/psychology ; Male ; Female ; Middle Aged ; Adult ; Aged ; *Self-Management/methods ; Focus Groups ; SARS-CoV-2 ; },
abstract = {BACKGROUND: An understanding of the nature of long Covid (LC) is evolving, with recent evidence highlighting the role of increased sympathetic activation and decreased parasympathetic response. Building upon this emerging science, the 'Transforming Long COVID' (TLC) programme was developed to support participants in their recovery by (i) introducing education on the neuroscience underpinning persistent symptoms (with a particular focus on the autonomic nervous system) and (ii) the development of self-management strategies to support recovery. The aim of this study was to examine the feasibility of the TLC programme with a cohort of people significantly affected by LC.<br><br>METHODS: Seventeen participants took part in the 8-week TLC programme which comprised of seven content sessions and one discussion (Q&amp;A) session. Participants completed survey scales (investigating anxiety, pain-related interference, pain catastrophising, sleep disturbance and fatigue) at baseline, immediately post-programme (at 8&#x2009;weeks), and retention (at 13&#x2009;weeks). Participants also took part in focus group interviews to investigate their experiences of the programme.<br><br>RESULTS: Fourteen participants (82%) attended at least six of the seven TLC content sessions. Decreases in mean values over time were observed across all measures, indicating a positive (non-significant) change. Participants reported an increase in understanding of LC, new hope for recovery, belief that they now had a realistic pathway for recovery, validation of their experiences and symptoms, meaningful improvements in function, and enhanced ability to respond to and attenuate physical symptoms. No adverse events were reported. Participants highlighted a number of programme strengths, along with some potential areas for improvement.<br><br>CONCLUSION: The TLC programme was shown to be feasible based on engagement, adherence, acceptable completion of surveys, and no adverse events. Study findings point to the potential for this programme to be refined, trialled and evaluated with a larger sample.<br><br>Four people (living with LC, ME/CFS, chronic migraine and chronic Lyme, fibromyalgia, and centralised pain syndrome), who have experience of applying a recovery approach aligned with the TLC programme, acted in a PPI (Public and Patient Involvement in research) capacity on this study. In addition, the lead author has personal experience with the illness, and developing the recovery approach, which helped inform programme structure and development [1]. These individuals provided advice and guidance on the potential structure for the group programme, course duration, tool selection, and language and wording of the programme and materials. Further detail is provided in the Supplementary Materials.},
}
@article {pmid42077647,
year = {2026},
author = {Lindberg, P and Wiqvist, S and Juszczyk, M and Lee, S and Kisiel, MA and Wachtler, C and Ståhlberg, M and Wheelock, &#xc5;M and Fedorowski, A and Carlsson, AC},
title = {Long COVID and risk of incident cardiovascular disease: a prospective cohort study using the Multimorbidity Integrated Registry Across Care Levels in Stockholm (MIRACLE-S) cohort.},
journal = {EClinicalMedicine},
volume = {94},
number = {},
pages = {103846},
pmid = {42077647},
issn = {2589-5370},
abstract = {BACKGROUND: Long COVID has emerged as a global health challenge, with increasing evidence of cardiovascular sequelae. Most previous studies have focused on hospitalised cohorts, whereas cardiovascular risk in community-managed long COVID cases remains less explored. We aimed to investigate the incidence of major cardiovascular events in individuals with long COVID compared to those without long COVID in a large population-based setting.<br><br>METHODS: Multimorbidity Integrated Registry Across Care Levels in Stockholm (MIRACLE-S) is a population-based cohort that covers all providers of healthcare for around 2.5 million residents in Stockholm County. Individuals aged 18-65 years with a physician-assigned long COVID diagnosis (ICD-10: U09.9) between October 2020 and January 2025 were identified. Exclusion criteria were hospitalisation for acute COVID-19 or pre-existing cardiovascular disease. Cox proportional hazards models estimated the effect of long COVID on a composite cardiovascular outcome (myocardial infarction, heart failure, cardiac arrhythmias, stroke, peripheral arterial disease), adjusting for demographic, lifestyle, and mental health factors.<br><br>FINDINGS: Among 1,217,693 individuals, 8999 (0.7%) had long COVID diagnosis (66% women). Cumulative incidence of any cardiovascular event was higher in long COVID group (women 18.2%, men 20.6%) compared with control group (women 8.4%, men 11.1%). In a fully adjusted model, long COVID was associated with the composite cardiovascular outcome (women HR 2.06, 95% CI 1.92-2.22; men HR 1.33, 1.20-1.48), cardiac arrhythmia (women HR 3.11, 2.85-3.39; men HR 1.61, 1.41-1.85), and coronary artery disease (women HR 1.25, 1.04-1.52; men HR 1.26, 1.05-1.51). Heart failure incidence was elevated in women only (HR 1.25, 1.00-1.55), as also was peripheral artery disease (HR 1.25, 1.05-1.50). Long COVID was not associated with stroke in either sex.<br><br>INTERPRETATION: Long COVID is associated with increased risk of incident cardiovascular disease, particularly cardiac arrhythmias, heart failure, and coronary artery disease. These findings underscore the need for systematic follow-up and integration of long COVID into cardiovascular risk assessment.<br><br>FUNDING: Region Stockholm and Heart Lung Foundation.},
}
@article {pmid42079856,
year = {2026},
author = {Yang, C and Mao, W and Senbaklavaci, &#xd6;},
title = {Editorial: Managing COVID-19 in heart and lung transplantation: clinical challenges and emerging solutions.},
journal = {Frontiers in surgery},
volume = {13},
number = {},
pages = {1843253},
pmid = {42079856},
issn = {2296-875X},
}
@article {pmid42080492,
year = {2026},
author = {Brady Sawant, H and Ross, D and Flannery, T and Tarrant, R and Haugh, J and Grimaldi, J and Mackreth, P and Sivan, M},
title = {Evaluating a Digital Patient Reported Outcome Measure for Long COVID in a Community Rehabilitation Service.},
journal = {Journal of primary care &amp; community health},
volume = {17},
number = {},
pages = {21501319261437896},
doi = {10.1177/21501319261437896},
pmid = {42080492},
issn = {2150-1327},
mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19/rehabilitation ; Male ; Female ; Middle Aged ; Adult ; Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Qualitative Research ; Mobile Applications ; Community Health Services ; },
abstract = {BACKGROUND: Long COVID presents with a wide range of persistent symptoms which can significantly affect daily functioning and increases pressure on already stretched National Health Service. A Digital Patient-Reported Outcome Measure application incorporating 4 outcome measure scales (COVID-19-Yorkshire Rehabilitation Scale, EuroQol 5 Dimension Scale, Modified Fatigue Impact Scale, and Medical Research Council Dyspnoea Scale) was introduced into a Long COVID community rehabilitation pathway in 2021. However, there was little known about its acceptability, uptake, or user experience.<br><br>METHODS: A qualitative service evaluation was conducted. Quantitative data was collected, over 2&#x2009;months, from 100 people using the service, including registration, usage patterns, and demographics. Semi structured questionnaires collected qualitative data from 20 participants. Template analysis was used to explore experiences, enablers, and barriers.<br><br>RESULTS: Of 100 participants, 38 were active app users, 46 were non active users, and 16 did not register. Engagement varied, depending on education employment status and digital literacy. Four themes emerged from qualitative data collected from 20 service users: Technology, Personal Experience, Symptom Tracking, and Support Requirements. Digital symptom monitoring was valued, but challenges were identified with navigation, clarity of the questions, guidance of use, and awareness of key functions such as symptom tracking graphs.<br><br>CONCLUSION(S): Opportunities were identified for development of the use of Digital Patient-Reported Outcome Measures. User feedback highlighted the need for improved usability, clearer information, and increased guidance to optimise engagement. These insights inform recommendations for the development and implementation of future Digital Patient Reported Outcome Measures.},
}
@article {pmid42082458,
year = {2026},
author = {Vilser, D and Han, I and Vogel, K and Jakobs, P and Lorenz, M and Huppke, P and Newman, L and Paszkier, M and Kuhle, J and Mohr, J and Aign, C and Reinhold, A and Reinhold, D and Weinzierl, S and Ullmann, E and Proquitté, H and Brunner-Weinzierl, MC},
title = {Immune-metabolic trajectories delineate subgroups in paediatric long COVID.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42082458},
issn = {2041-1723},
support = {Br1860/18//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 01EP2101//Bundesministerium f&#xfc;r Bildung und Forschung (Federal Ministry of Education and Research)/ ; },
mesh = {Humans ; *COVID-19/immunology/metabolism/virology ; Child ; Male ; Adolescent ; Female ; SARS-CoV-2/immunology ; Child, Preschool ; Metabolomics ; Cytokines/immunology/metabolism ; Infant ; Autoantibodies/immunology/blood ; Cohort Studies ; },
abstract = {Most children and adolescents recover rapidly from SARS-CoV-2 infection, yet a subset develops paediatric long COVID (LC). How immune ontogeny shapes LC biology and heterogeneity remains unclear. We deeply phenotype a two-visit cohort with severe LC (n = 74) and controls (n = 27) spanning up to 3.2 years post index infection. Symptom burden remains high and neurofilament light chain (NfL) percentiles inversely associate with functional status (Bell score; r = -0.3536, P = 0.0060). Cardiopulmonary assessment and serology are unremarkable. Conventional autoantibodies are not enriched, whereas anti-DFS70 supports subgrouping. Immune features are temporally structured; SARS-CoV-2-associated mediators decline within 1 year, while innate-weighted, Th2-skewed cytokines persist. Metabolomics (43 metabolites) recapitulate the identified subgroups and align with EBV serostatus, disease phase (<1 year versus years 1-3.2), and anti-DFS70 positivity. In EBV-naïve LC, higher haemoglobin concentration (MCHC) tracks worse function, whereas higher IL-12p40, thiamine and basophils track milder impairment (all P ≤ 0.0170). These data delineate immune-metabolic and haematological axes of paediatric LC heterogeneity and support biomarker-guided stratification.},
}
@article {pmid42082813,
year = {2026},
author = {Donath, Q and Haegele, M and Schindler, D and Welzhofer, T and Christa, C and Grabbe, A and Leone, A and Ilhan, C and Weidmann, C and Eberhartinger, M and Bechtold, S and Bursch, N and Wolf, H and Hieber, H and Peo, LC and Bucka, LA and Stojanov, S and Warlitz, C and Alberer, M and Gerrer, K and Hausruckinger, A and Mittelstrass, K and Wendtner, CM and Hoechstetter, MA and Grübl, A and Toepfner, N and Pricoco, R and Scheibenbogen, C and Mihatsch, LL and Behrends, U},
title = {Risk factors for severe post-COVID condition in children, adolescents, and young adults.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
pmid = {42082813},
issn = {1432-1076},
support = {2490-PCS-2023-V13, 2490-PC-2021-V6-D44360/2021//Bavarian State Ministry of Health and Care/ ; },
mesh = {Humans ; Adolescent ; Child ; Female ; Male ; *COVID-19/complications/epidemiology/diagnosis ; Risk Factors ; Young Adult ; Severity of Illness Index ; Germany/epidemiology ; Adult ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Registries ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; },
abstract = {Post-COVID condition (PCC) in children and young people (CYP, PCCcyp) remains a significant health burden. Early identification of patients at risk for severe disease, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is crucial for timely and adequate care. This monocentric, observational registry study, performed at a tertiary pediatric hospital in Germany, included CYP aged 7-25 years with PCCcyp at diagnosis. Standardized clinical assessment tools and patient-reported outcome measures were applied, including the novel Munich Long COVID Symptom Questionnaire (MLCSQ). Severe PCC was defined by chronic symptom clusters, Fatigue Severity Scale (FSS), Total Composite Autonomic Symptom Score-31 (COMPASS-31), SF-36 composite scores, Bell Score, and confirmed ME/CFS diagnosis. Among 120 participants, severe PCCcyp was associated with a higher number of acute symptoms (ORadj 1.22, P < 0.001), acute orthostatic intolerance (ORadj 9.87, P = 0.002), acute trouble concentrating (ORadj 11.8, P = 0.005), and female sex (OR 3.31, P = 0.031). Categorizing acute symptoms at a threshold of ≥ 12 yielded optimal model performance (AUC 0.857; sensitivity 65.6%; specificity 90.2%). ME/CFS was diagnosed in 24% of participants, all within the severe PCCcyp cluster, and was characterized by greater acute symptom complexity, more fatigue, more autonomic symptoms, and poorer function. Conclusions: The number and pattern of acute symptoms during SARS-CoV-2 infection may serve as early, specific predictors of severe PCCcyp. Patients with ≥ 12 acute symptoms should be closely monitored to enable early diagnosis of severe PCCcyp and ME/CFS. A distinct cluster of severely affected patients, frequently with ME/CFS, was identified.Trial registration: ClinicalTrials.gov: NCT05638724; Ethics approval (511/21, 2025-465-S-SB).},
}
@article {pmid42068900,
year = {2026},
author = {Liira, H and Varonen, M and Vangelova-Korpinen, V and Venäläinen, MS and Arokoski, J and Kvarnström, K and Vuokko, A and Malmivaara, A},
title = {Somatic symptom burden and distress in post COVID-19 and persistent physical symptoms: Evidence from combined SSD-12 and PHQ-15 factor analysis.},
journal = {Journal of psychosomatic research},
volume = {208},
number = {},
pages = {112686},
doi = {10.1016/j.jpsychores.2026.112686},
pmid = {42068900},
issn = {1879-1360},
abstract = {BACKGROUND AND AIM: Post COVID-19 condition (PCC) and persistent physical symptoms (PPS) may involve overlapping symptom presentations. We examined whether symptom-related dimensions differ or overlap between PCC and functional somatic disorders by comparing Somatic Symptom Disorder-B Criteria Scale (SSD-12; cognitive-affective distress) and the Patient Health Questionnaire-15 (PHQ-15; somatic symptom burden), and by performing a joint factor analysis of their items.<br><br>METHODS: Two cohorts at Helsinki University Hospital were analysed: the Sympa cohort (2020-2024), comprising patients with PPS, and the Long Covid (LC) cohort (2021-2023), including patients with PCC and age- and sex-matched controls.<br><br>RESULTS: The study included 557 patients with PPS, 433 with PCC, and 197 controls; two-thirds of patients in both cohorts were female. Patients showed markedly higher somatic symptom burden than controls, with 52.2% of patients with PPS and 48.0% of those with PCC exceeding the combined SSD-12 and PHQ-15 threshold indicating concurrent high somatic symptom burden and symptom-related distress. Joint factor analysis revealed a four-factor structure: one dominant cognitive-affective distress factor; a narrower persistence-worry factor; and two symptom clusters reflecting pain/gastrointestinal and autonomic-neurological symptoms. Participants above the threshold had poorer quality of life, lower resilience, and more comorbidities and symptoms across cohorts (all p&#xa0;<&#xa0;0.001).<br><br>CONCLUSIONS: Approximately half of rehabilitation clinic patients with PPS or PCC exhibited high somatic symptom burden and symptom-related distress. Despite differing clinical entry points, the two cohorts showed broadly similar symptom-related dimensions. High symptom-related distress identifies a subgroup with greater impairment who may benefit from targeted rehabilitation approaches.},
}
@article {pmid42071077,
year = {2026},
author = {Nielsen, NM and Spiliopoulos, L and Sørensen, AIV and O'Regan, E and Bager, P and Ethelberg, S and Koch, A and Videbech, P and Hviid, A},
title = {Acute SARS-CoV-2 infection and self-reported post-acute cognitive dysfunctions from the Danish EFTER-COVID survey.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {42071077},
issn = {2730-664X},
abstract = {BACKGROUND: The extent and burden of post-acute cognitive dysfunctions following SARS-CoV-2 infection is uncertain.<br><br>METHODS: 25,485 SARS-CoV-2 test-positive and 25,032 test-negative individuals were repeatedly asked to score symptoms of subjective cognitive deficits 2 to 18 months after test using the "Cognitive complaints in bipolar disorder rating assessment" (COBRA) tool. Poisson mixed-effects models were used to estimate Score Ratios (SRs) by comparing scores between test-positive and test-negative individuals.<br><br>RESULTS: At each follow-up point, test-positive individuals have low but slightly higher mean COBRA scores compared with test-negatives. For the combined 2-18 months period, COBRA scores among test-positive individuals are 11% higher than corresponding scores among test-negatives (SR2-18mth&#x2009;=&#x2009;1.11 (95% CI; 1.09-1.13)). Of effect modifiers explored, being hospitalized with a positive SARS-CoV-2 test particularly elevates COBRA scores (SR2-18mth&#x2009;=&#x2009;1.38 (95% CI; 1.24-1.54)).<br><br>CONCLUSION: In the general population of SARS-CoV-2 infected individuals, self-reported post-acute scores of cognitive dysfunctions are low and only slightly higher than corresponding scores among test-negatives. Higher COBRA scores among hospitalized SARS-CoV-2 test positives corroborate with long-term cognitive impairment being most pronounced among those with severe SARS-CoV-2 infection.},
}
@article {pmid41872922,
year = {2026},
author = {Cohen, JG and Estopier-Castillo, V and Olivier, C and Destors, M and Ferretti, GR and Pépin, JL and Tamisier, R and Bayat, S},
title = {Imaging biomarkers of post-COVID dyspnea: insights from machine learning CT patterns and parametric response mapping.},
journal = {Respiratory research},
volume = {27},
number = {1},
pages = {},
pmid = {41872922},
issn = {1465-993X},
abstract = {BACKGROUND: Dyspnea is one of the most common symptoms in the post-acute phase of COVID-19 pneumonia. Conventional pulmonary function tests and computed tomography (CT) scores often fail to show correlation with symptom severity, highlighting the need for more sensitive imaging biomarkers. Machine-learning–based quantitative CT analysis and parametric response mapping (PRM) can capture subtle structural and functional abnormalities that may be associated with persistent dyspnea.<br><br>METHODS: We analyzed inspiratory and paired inspiratory&#x2013;expiratory CT scans of early (3&#x2013;6 months) post-COVID-19 pneumonia patients. Inspiratory CT images were segmented using a random forest algorithm to quantify lung parenchymal patterns. Paired inspiratory/expiratory scans were co-registered to derive ventilation metrics and PRM-defined functional small airway disease (fSAD), emphysema, emptying emphysema, and normal lung. Associations between imaging metrics and patient-reported dyspnea assessed by a visual analogue scale (VAS) were evaluated using univariable and multivariable linear regression, with adjustment for age, sex, BMI, and smoking history.<br><br>RESULTS: One hundred twenty-three patients had usable inspiratory CT scans, and 116 patients had paired inspiratory/expiratory scans of sufficient quality for analysis. In the adjusted multivariable models, greater PRM-defined functional small airway disease (fSAD) was positively associated with dyspnea (standardized &#x3b2;&#x2009;=&#x2009;1.21, p&#x2009;=&#x2009;0.002). Moreover, a lower standard deviation of dense ground-glass attenuation in the left lung (standardized &#x3b2; = &#x2212;0.82, p&#x2009;=&#x2009;0.033) and greater total volume of dense ground-glass opacities (standardized &#x3b2;&#x2009;=&#x2009;0.71, p&#x2009;=&#x2009;0.033) were independently associated with dyspnea.<br><br>CONCLUSIONS: In early post-COVID-19 pneumonia, machine-learning&#x2013;based CT pattern recognition and PRM revealed that functional small airway disease, and the total volume and heterogeneity of lung dense ground-glass opacities are significantly associated with persistent dyspnea. These findings highlight the potential of quantitative CT to identify pulmonary imaging biomarkers relevant to long COVID symptom burden.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov (NCT04406324).},
}
@article {pmid42063202,
year = {2026},
author = {Neilens, H and Allgar, V and Sands, KA and Chynoweth, J and Lord, A and Aspinall, PJ and Hambly, H and Barnett, A and Skipper, L and Bewick, T and Maidment, I and Razak, HA and Ashton, R and Strain, D and Knapp, K and Faghy, MA},
title = {An open-label, clinical feasibility study of the efficacy of Remdesivir for Long-COVID.},
journal = {Pilot and feasibility studies},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40814-026-01823-9},
pmid = {42063202},
issn = {2055-5784},
abstract = {BACKGROUND: Long COVID (LC) affects around two million people in the UK and over 65 million people globally. Antiviral medications have shown positive effects in reducing the risk of progression to severe disease in high-risk patients during an acute SARS-CoV-2 infection and have improved outcomes in those living with LC. Research testing the feasibility and efficacy of antiviral medications is ongoing, and clinical trials should determine the use of Remdesivir and its impact on LC symptoms, patient-reported outcomes, quality of life and functional status.<br><br>METHODS: Seventy-two patients&#x2009;&#x2265;&#x2009;18&#xa0;years of age who have a confirmed LC diagnosis will be recruited across two sites to trial RemdesivirTM treatment delivered via intravenous infusion over 5&#xa0;days. This feasibility study will provide high-quality data to estimate screening rates, recruitment through different pathways, retention and treatment adherence. The study will also determine the definitive trial's most clinically relevant primary outcome. After a detailed screening process, patient-reported and clinical outcome measures (including EQ-5D-5L, Symptom Burden Questionnaire&#x2122; for LC (SBQ&#x2122;), cardiopulmonary exercise tests (CPET), lung function, biomarkers and inflammatory profiles) will be collected to determine symptoms and impact of their condition, which will be repeated post-treatment. A subset of 20 participants will undergo whole-body&#xa0;parametric Fluorodeoxyglucose (FDG) PET/CT&#xa0;to measure multi-organ metabolic activity. Due to the established physical, cognitive and clinical impairment impacts of LC, patient involvement has been extensively embedded within the design and implementation of all study processes to increase patient safety and delivery.<br><br>DISCUSSION: This study will provide data on the feasibility of a trial of 5-day intravenous treatment with Remdesivir for patients with LC. The treatment is already effective in the treatment of patients with acute severe cases of SARS-CoV-2. Remdesivir has an established safety profile and carries no higher risk to patients than standard medical care. The findings will inform the design of a future definitive study.<br><br>TRIAL REGISTRATION: ISRCTN Number: 72940450. Date registered: 07/06/2024. URL: https://www.isrctn.com/ISRCTN72940450.<br><br>CLINICALTRIALS: gov Number: NCT05911906.},
}
@article {pmid42063762,
year = {2026},
author = {Spanoghe, M and Molmans, THJ and Antonacci, T and Burel, E and Herschke, F and Schneider, N and Oustric, P and Thielemans, P and Nicolas, JB and Dauby, N and Nicaise, C and Van Weyenbergh, J and Jamoulle, M},
title = {Commentary: Internal medicine at the crossroads of long COVID diagnosis and management.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1798119},
pmid = {42063762},
issn = {2296-858X},
}
@article {pmid42065099,
year = {2026},
author = {Tuller, D},
title = {Comments regarding "Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials".},
journal = {EClinicalMedicine},
volume = {95},
number = {},
pages = {103882},
pmid = {42065099},
issn = {2589-5370},
}
@article {pmid42065101,
year = {2026},
author = {Tan, C and Meng, J and Dai, X and Gao, S},
title = {Authors' reply: Comments regarding "Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials".},
journal = {EClinicalMedicine},
volume = {95},
number = {},
pages = {103883},
pmid = {42065101},
issn = {2589-5370},
}
@article {pmid42066215,
year = {2026},
author = {Maeda, T and Yohannes, AM},
title = {Expanding Pulmonary Rehabilitation Beyond Chronic Obstructive Pulmonary Disease and Long COVID: ITS ROLE IN COMPARATIVE EVIDENCE.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {46},
number = {3},
pages = {155-157},
pmid = {42066215},
issn = {1932-751X},
}
@article {pmid41410968,
year = {2025},
author = {Stafseth, M},
title = {[Long COVID].},
journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke},
volume = {145},
number = {15},
pages = {},
doi = {10.4045/tidsskr.25.0629},
pmid = {41410968},
issn = {0807-7096},
}
@article {pmid42056917,
year = {2026},
author = {Bergqvist, E and Valerio-Shewmaker, M and Swartz, M and Patel, J and Padilla, L and Amavisca, XF and Gandhi, H and Messiah, SE},
title = {Association of race, ethnicity, and pediatric long COVID and MIS-C: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-12848-z},
pmid = {42056917},
issn = {1471-2334},
}
@article {pmid42057113,
year = {2026},
author = {Heemskerk, SCM and Brus, IM and de Groot, A and Rijssenbeek-Nouwens, L and Tieleman, P and Ter Wolbeek, M and Burdorf, A and Biere-Rafi, S and Haagsma, JA},
title = {Opportunities and barriers in care for patients with post COVID-19 condition: a Delphi study among healthcare workers.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14489-z},
pmid = {42057113},
issn = {1472-6963},
}
@article {pmid42059350,
year = {2026},
author = {Loblundo, C and Chun, WB and Nguyen, SA and Meenan, K and O'Rourke, AK},
title = {Laryngeal Dysfunction Following COVID-19: A TriNetX Retrospective Cohort Study.},
journal = {The Laryngoscope},
volume = {},
number = {},
pages = {},
doi = {10.1002/lary.70590},
pmid = {42059350},
issn = {1531-4995},
abstract = {OBJECTIVE(S): Long COVID affects multiple organ systems, yet the incidence and risk factors for post-COVID-19 laryngeal dysfunction remain underexplored. This study evaluated the incidence of laryngeal dysfunction following COVID-19.<br><br>METHODS: A retrospective cohort study was performed using the TriNetX Global Collaborative EHR Network (>&#x2009;180 million records). Adults without prior laryngeal dysfunction or major comorbidities were stratified by COVID-19 exposure and compared with uninfected controls. Outcomes included chronic cough, dysphagia, voice disorders, vocal fold paralysis, and laryngeal spasm, assessed up to 5&#x2009;years post-infection. After propensity score matching, odds ratios (OR) and risk differences (RD) with 95% confidence intervals (CI) were calculated.<br><br>RESULTS: COVID-19 was associated with significantly increased odds of chronic cough (peak OR 7.12; RD 0.33%, p&#x2009;<&#x2009;0.0001), dysphagia (peak OR 2.71; RD 0.36%, p&#x2009;<&#x2009;0.0001), voice disorders (peak OR 3.25; RD 0.12%, p&#x2009;<&#x2009;0.0001), vocal fold paralysis (peak OR 2.17; RD 0.01%, p&#x2009;<&#x2009;0.0001), and laryngeal spasm (peak OR 2.79; RD 0.003%, p&#x2009;<&#x2009;0.0001). Incidence peaked at 1-2&#x2009;years for most outcomes and at 2-3&#x2009;years for laryngeal spasm. Hospitalization and mechanical ventilation were associated with increased rates of dysphagia (HR 2.63; HR 5.26), voice disorders (HR 1.15; HR 4.45), and vocal cord paralysis (HR 2.09; HR 9.35), but reduced rates of chronic cough (HR 0.68; HR 0.45). Vaccinated patients showed higher rates of chronic cough (HR 1.36) and voice disorders (HR 1.22).<br><br>CONCLUSION: COVID-19 is associated with increased incidence of new-onset laryngeal dysfunction, most commonly peaking 1-2&#x2009;years after infection and influenced by hospitalization, mechanical ventilation, and vaccination status.},
}
@article {pmid42059960,
year = {2026},
author = {Tuomaala, J and Saraste, M and Smith, E and Kuusi, M and Westerberg, E and Honkonen, E and Kargar, R and Laaksonen, S and Lehto, J and Luoma, A and Matilainen, M and Misin, O and Atosuo, J and Kanerva, M and Liira, H and Laakso, S and Posharina, T and Saunavaara, V and Wahlroos, S and Rajander, J and Airas, L},
title = {Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study.},
journal = {Journal of neurology},
volume = {273},
number = {5},
pages = {},
pmid = {42059960},
issn = {1432-1459},
support = {330902//Academy of Finland/ ; 374291//Academy of Finland/ ; 337530//Academy of Finland/ ; 357910//Academy of Finland/ ; 358823//Academy of Finland/ ; 101057553//HORIZON EUROPE Health/ ; },
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/psychology/metabolism ; Male ; Female ; Adult ; Positron-Emission Tomography ; Middle Aged ; *Receptors, GABA/metabolism ; *Neuroglia/metabolism ; *Limbic System/diagnostic imaging/metabolism ; Multiple Sclerosis/diagnostic imaging/metabolism/psychology ; Magnetic Resonance Imaging ; *Mental Disorders/diagnostic imaging/etiology ; },
abstract = {BACKGROUND: A subset of individuals experience prolonged neurological and psychiatric symptoms following SARS-CoV-2 infection, a condition referred to as long COVID (LC). Limited evidence implicates ongoing neuroinflammatory processes as a driver of LC. This study investigates neuroinflammation in LC using translocator protein positron emission tomography (TSPO PET).<br><br>METHODS: 14 LC, 11 healthy control (HC) and 13 multiple sclerosis (MS) participants were included in the study. They underwent [[11]C]PK11195 TSPO PET and 3T magnetic resonance imaging (MRI) to evaluate glial activation, white matter (WM) pathology and brain volumetrics. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured as markers of neuronal and glial damage. LC participants completed neurological examinations and mental health assessments.<br><br>RESULTS: TSPO availability, measured as distribution volume ratio (DVR), was not elevated in LC compared to HCs but was significantly lower in LC compared to MS (WM DVR 1.03 vs. 1.06; p&#x2009;=&#x2009;0.007). Individuals imaged within 16&#xa0;months of SARS-CoV-2 infection showed higher WM DVR compared to those with a longer disease duration (1.05 vs. 1.02; p&#x2009;=&#x2009;0.04). Moreover, lower quality of life was associated with higher DVRs in the hippocampus, amygdala and thalamus (&#x3c1;&#x2009;= -&#x2009;0.83-&#x2009;-&#x2009;0.70), and depression and anxiety correlated positively with DVRs in the hippocampus and amygdala (&#x3c1;&#x2009;=&#x2009;0.75-0.97).<br><br>CONCLUSIONS: LC TSPO availability did not differ from HCs in any studied brain area. However, lower WM TSPO availability in individuals with longer LC duration suggests COVID-19-associated neuroinflammation may subside with time, while the association between limbic TSPO availability and LC severity may imply a role for limbic activity in LC symptomology.},
}
@article {pmid42061273,
year = {2026},
author = {Jürgensen, M and Frisk, B and Kvale, G and Espehaug, B},
title = {Improvements in long COVID symptoms, functional level and the impact of illness perceptions after concentrated micro-choice-based rehabilitation: A1-year prospective uncontrolled study.},
journal = {Journal of psychosomatic research},
volume = {208},
number = {},
pages = {112687},
doi = {10.1016/j.jpsychores.2026.112687},
pmid = {42061273},
issn = {1879-1360},
abstract = {BACKGROUND: Patients with long COVID face persisting physical and psychiatric symptoms. Illness perceptions are associated with increased symptom burden and poorer recovery. However, little is known about how changes in illness perceptions in rehabilitation impact symptoms and functional levels. This study assessed longitudinal changes in symptoms of anxiety and depression, insomnia, fatigue, dyspnea, illness perception, and functional levels in patients with long COVID following a micro-choice-based intervention.<br><br>METHODS: This prospective uncontrolled study with 12-month follow-up included 78 patients with long COVID aged 19-67&#xa0;years, mean age 40.3&#xa0;&#xb1;&#xa0;12.0&#xa0;years. The intervention consisted of three equally important phases: pre-treatment preparation, a 3-day concentrated micro-choice-based intervention and integration of changes into daily life.<br><br>RESULTS: At 3- and 12-month follow-ups significant improvements were observed in symptoms of anxiety (p&#xa0;<&#xa0;0.001), depression (p&#xa0;<&#xa0;0.001), fatigue (p&#xa0;<&#xa0;0.001), illness perceptions (p&#xa0;<&#xa0;0.001) and functional levels (p&#xa0;<&#xa0;0.001). Caseness of anxiety and depression were reduced from 26.9% at baseline to 10.0% 12-month follow-up and from 51.3% to 20.0%, respectively. Changes in functional level strongly correlated with changes in illness perception. Patients with a history of psychiatric illness did not experience the same short-term improvements in illness perception compared to those without such a history, but theses differences were not present at 12-month follow-up.<br><br>CONCLUSION: Patients with long COVID participating in a concentrated micro-choice-based rehabilitation showed consistent improvements in both psychiatric symptoms and functional levels, including those with a history of psychiatric illness. Changes in illness perception was associated with sustained reduction in symptom burden and increased functional levels.<br><br>CLINICAL TRIALS REGISTRATION: NCT05234281, with an approval date of 10 February 2022. The study were approved by the Western Norway Regional Committees for Medical and Health Research Ethics (REK 2020/101648).},
}
@article {pmid42051331,
year = {2026},
author = {Wilches-Luna, EC and Perez-Hortúa, V and Asencio-Santofimio, H and Aguilar-Zambrano, J and Arzayus-Patiño, L},
title = {Distribution of pulmonary ventilation in women with post-COVID-19 before and after the use of a respiratory incentive device (UBICU): a pilot study.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1789878},
pmid = {42051331},
issn = {2673-253X},
abstract = {INTRODUCTION: In the aftermath of the COVID-19 pandemic, restrictive pulmonary complications have emerged as a common long-term sequela. To address these impairments, a novel flow-based respiratory incentive device, UBICU, was developed to promote lung expansion through gamification and visual feedback. The aim of this study was to describe the pulmonary ventilation distribution using Electrical Impedance Tomography (EIT) in women with long COVID and restrictive pulmonary impairment, before and after using the UBICU device.<br><br>METHODS: This exploratory (pre-post) pilot study included eight women with post-COVID-19 restrictive impairment, as determined by spirometry in accordance with ATS/ERS guidelines. Pulmonary ventilation distribution was assessed before and after the intervention using electrical impedance tomography. Participants were provided with the UBICU device and instructed to perform three sets of 10 repetitions daily for seven consecutive days. The study was approved by the Institutional Ethics Committee, adhered to the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants.<br><br>RESULTS: An asymmetric regional ventilation pattern was observed before and after the intervention. Statistically significant improvements were found in ROI 1 (p&#x2009;=&#x2009;0.007), ROI 3 (p&#x2009;=&#x2009;0.007), and ROI 4 (p&#x2009;=&#x2009;0.007) after using the UBICU device.<br><br>CONCLUSION: Use of the UBICU device was associated with improvements in pulmonary ventilation distribution, suggesting its potential as an adjunctive therapeutic tool in the management of women with long COVID and restrictive pulmonary impairment.},
}
@article {pmid42051540,
year = {2026},
author = {Jin, H and An, Y and Huang, J and Luo, T and Wu, X},
title = {Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1774310},
pmid = {42051540},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications/metabolism/physiopathology ; *SARS-CoV-2 ; *Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism ; Exercise/physiology ; Mitochondria/metabolism ; Neuroimmunomodulation ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species/metabolism ; },
abstract = {Post-exertional malaise (PEM) is a common core symptom in various chronic debilitating conditions, such as Post COVID-19 Condition (PCC, also known as Long COVID) and Chronic Fatigue Syndrome (CFS). It is characterized by the delayed and persistent exacerbation of symptoms following even mild physical or cognitive activities. This review presents a systematic review of the pathophysiological mechanisms involved in PEM, proposing a dynamic framework of multi-system interactions that may lead to homeostatic imbalance. The etiology of PEM is multifactorial, potentially involving factors such as the persistent presence of pathogens, exposure to environmental toxins, and genetic predisposition. Collectively, these factors may establish a vulnerable baseline that heightens the body's physiological response to stressors, such as exercise, potentially triggering a pathological reaction. First, mitochondrial dysfunction and metabolic abnormalities may act as potential initiating factors in PEM, manifesting as impaired ATP synthesis, overproduction of reactive oxygen species (ROS), and the accumulation of metabolic byproducts. It is crucial to emphasize that exercise itself induces a 'toxic excitatory effect,' whereby healthy individuals enhance mitochondrial function and antioxidant defenses through physical activity. However, in individuals predisposed to PEM, due to underlying pathological conditions (e.g., sequelae of viral infections), this adaptive process is disrupted, preventing effective restoration of mitochondrial homeostasis and may initiate a potential vicious cycle of dysfunction. Second, ROS and mitochondrial DNA (mtDNA), as damage-associated molecular patterns (DAMPs), along with pathogen-associated molecular patterns (PAMPs), may activate the NLRP3 inflammasome and induce the release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, potentially transforming localized metabolic stress into a systemic inflammatory response. Subsequently, peripheral inflammation may be transmitted to the central nervous system through disruption of the blood-brain barrier and vagal nerve pathways, activating glial cells and initiating neuroinflammation. This process may ultimately affect the brain's interoceptive network, particularly the insular cortex, resulting in altered perception and processing of signals related to fatigue and pain. Furthermore, mitochondrial dysfunction in neurons may contribute to central energy depletion, which may impair synaptic plasticity and induce cognitive deficits and brain fatigue. Ultimately, this review proposes that PEM may arise from a complex interplay among mitochondrial dysfunction, immune activation, and neuroinflammation, which together form a self-perpetuating loop of "energy exhaustion - inflammation amplification," potentially contributing to the chronic and multi-system nature of PEM symptoms. The integrated "metabolism-immune-neuro" interaction model presented in this article may provide a potential comprehensive framework for understanding PEM and highlights the need for a multi-target, collaborative intervention approach that may help disrupt the pathological cycle.},
}
@article {pmid42052332,
year = {2025},
author = {Lee, EJ and Tsang, C and Pérez, MLG and Abouzari, M and Djalilian, HR},
title = {Calcitonin Gene-Related Peptide-Induced Central Sensitization: A Hypothesis for Long COVID Symptoms.},
journal = {Medical hypotheses},
volume = {195},
number = {},
pages = {},
pmid = {42052332},
issn = {1532-2777},
abstract = {Central sensitization (CS) denotes aberrant processing of sensory stimuli within the central nervous system, wherein innocuous inputs activate pain pathways, leading to pain hypersensitivity. Features observed in CS conditions are often present in patients with long COVID, suggesting a potentially shared pathophysiological mechanism. We hypothesize that elevated levels of calcitonin gene-related peptide (CGRP), a neuropeptide known to play an integral role in the development of CS, may contribute to the persistent symptoms observed in long COVID. This article explores the role of CGRP within the context of CS and proposes its potential relationship to long COVID.},
}
@article {pmid42052381,
year = {2026},
author = {Lin, J and Chen, S and Zhang, L and Qiu, M and Zuo, W and Wang, L and He, Q and Li, Y and Jin, H and Tan, S and Huang, M and Zhu, C and Jin, Q and Wang, M and Wan, Y and Hu, B},
title = {Two-year trajectory of cognitive decline and neurological sequelae in COVID-19 survivors with acute neurological symptoms.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1724803},
pmid = {42052381},
issn = {1663-4365},
abstract = {INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 has profound implications for global public health. It significantly affects the nervous system and cognitive function. The emergence of long COVID has raised concerns regarding long-term cognitive impairment, particularly among patients who experienced neurological symptoms during the acute phase of infection.<br><br>AIM: This study investigated the impact of neurological symptoms during acute SARS-CoV-2 infection on subsequent cognitive change and neurological sequelae over a 2-year period.<br><br>METHODS: We enrolled 3,419 hospitalized patients with confirmed infection in Wuhan, China (Dec 2022-Mar 2023), and 2,087 completed follow-ups. Propensity score matching identified 901 patients with acute neurological symptoms and 901 controls. Cognitive decline was measured with the Informant Questionnaire on Cognitive Decline in the Elderly, and cognitive status with the Telephone Interview of Cognitive Status-40. Multivariable regression was used to examine risk factors and cognitive changes, and residual neurological symptoms and new-onset symptoms were also analyzed.<br><br>RESULTS: Acute neurological symptoms, particularly central nervous system manifestations such as delirium and brain fog, were strongly associated with both cognitive decline (aOR, 2.16; 95% CI, 1.53-3.07) and cognitive impairment (aOR, 2.75; 95% CI, 1.73-4.49). Delirium, brain fog, stroke, numbness, and facial paralysis were associated risk factors (all p < 0.05). After 2 years' follow-up, most acute neurological symptoms had subsided, yet fatigue (8.66%) and brain fog (5.99%) persisted. Comorbidities did not significantly increase the risk of persistent symptoms. For the new-onset symptoms, the proportion of insomnia, tinnitus, blurred vision, movement disorder, palpitation, muscle weakness, and respiratory symptoms were much higher in the neurological symptom group (p < 0.05), with a highest proportion in insomnia (9.99% vs. 5.22%, p < 0.001), compared with the non-neurological symptom group.<br><br>CONCLUSION: Acute neurological symptoms, especially central nervous system manifestations, were strongly associated with long-term cognitive decline and new-onset symptoms (mainly insomnia) in COVID-19 survivors. This study uniquely reveals the persistence of high levels in brain fog and fatigue at 2-year's follow up, despite overall subsidence of most acute manifestations, underscoring the need for early intervention and sustained monitoring in this high-risk population.},
}
@article {pmid42052408,
year = {2026},
author = {Wang, R and Dai, R and Dai, H and French, E and Zheng, C},
title = {Controlling FDR in selecting group-level simultaneous signals from multiple data sources with application to the National COVID Collaborative Cohort data.},
journal = {Journal of applied statistics},
volume = {},
number = {},
pages = {},
pmid = {42052408},
issn = {0266-4763},
abstract = {One challenge in exploratory association studies using observational data is that the associations between the predictors and the outcome are potentially weak and rare, and the candidate predictors have complex correlation structures. False discovery rate (FDR) controlling procedures can provide important statistical guarantees for replicability in predictor identification in exploratory research. In the recently established National COVID Collaborative Cohort (N3C), electronic health record (EHR) data on the same set of grouped candidate predictors are independently collected in multiple different data contributing sites, offering opportunities to identify true associations by combining information from different sources. One challenge is to handle the heterogeneous data types for the same clinical endpoint from the multiple sites. This paper addresses this challenge by presenting a general knockoff-based variable selection algorithm to identify associations from unions of group-level conditional independence tests (simultaneous signals) with exact FDR control guarantees under finite sample settings. This algorithm can work with general regression settings, allowing heterogeneity of both the predictors and the outcomes across multiple data sources. We demonstrate the performance of this method with extensive numerical studies and an application to the N3C data.},
}
@article {pmid42053865,
year = {2026},
author = {Mignolet, M and Deroux, C and Florkin, T and Bielarz, V and De Swert, K and Halloin, N and Sprimont, L and Ladang, A and George, F and Gilloteaux, J and Abeloos, L and Garin, P and Van Weyenbergh, J and Jamoulle, M and Diederich, C and Gillet, NA and Bulpa, P and Nicaise, C},
title = {Pathogenic IgG from long COVID patients with neurological sequelae triggers sensitive but not cognitive impairments upon transfer into mice.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {42053865},
issn = {1432-0533},
mesh = {Animals ; *COVID-19/immunology/complications/psychology ; *Immunoglobulin G/immunology ; Mice ; Humans ; Male ; Female ; Mice, Inbred C57BL ; *Cognitive Dysfunction/immunology/etiology ; Middle Aged ; *Autoantibodies/immunology ; SARS-CoV-2 ; Hyperalgesia/immunology ; Disease Models, Animal ; Adult ; Aged ; },
abstract = {Approximately 30% of long COVID patients still experience neurological symptoms (brain fog, pain, chronic fatigue) more than 4 months after the onset of COVID-19. This condition, known as 'neurological long COVID', remains poorly understood and might be explained by a persisting autoimmune response against nervous-derived self-antigens. The aim of this study is to determine whether IgG autoantibodies from long COVID patients with neurological sequelae can bind to central or peripheral nervous system epitopes and trigger neuropsychiatric symptoms upon passive transfer into mice, thereby mirroring patient-reported manifestations. Long COVID patients meeting the 2021 consensus WHO definition were included following a standardized neuropsychological assessment, while excluding patients with a medical history of autoimmune and neurological disorders. Age- and sex-matched asymptomatic individuals were used as healthy controls. Total IgGs were isolated using protein G purification and injected intraperitoneally into C57Bl6/J mice for four consecutive days. During the two weeks post-injections, behavioral tests assessed mechanical allodynia, thermal hyperalgesia, spatial working memory, depression, and anxiety. Mice injected with IgG from long COVID patients showed no difference with the control group in terms of anxiety or depression behaviors, short- or long-term spatial memories. However, they displayed a transient decrease of paw withdrawal threshold and thermal hypersensitivity during the first week. This effect was abolished when IgG-depleted serum or papain-digested IgGs were transferred. IgG from long COVID patients accumulated in the lumbar dorsal root ganglia of injected mice and colocalized with proprioceptive and nociceptive sensory neurons, without inducing local neuroinflammation or astrogliosis. When applied onto human post-mortem DRG tissue, patient-derived IgG also exhibited immunoaffinity for sensory neuron somata. These data demonstrate that IgGs from long COVID patients bind to peripheral sensory neurons and induce pain-related symptoms in mice. Our findings also support the hypothesis that autoantibodies mediate pain-related pathophysiology in the spectrum of long COVID symptoms.},
}
@article {pmid42055117,
year = {2026},
author = {Kahlon, RK and Laurin, JKH and Nath, E and Raj, SR},
title = {Successful Ivabradine Use Throughout Pregnancy for Postural Orthostatic Tachycardia Syndrome: A Case Report with Reassuring Maternal-Fetal Outcomes.},
journal = {The Canadian journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cjca.2026.04.019},
pmid = {42055117},
issn = {1916-7075},
abstract = {We report on a 35-year-old gravida 2 para 1 female with long-COVID postural orthostatic tachycardia syndrome (POTS) who continued all pharmacologic therapies from preconception through delivery, including ivabradine, a medication contraindicated in pregnancy due to preclinical embryotoxicity and teratogenicity. Serial fetal assessments including growth studies, fetal Dopplers, and non-stress tests remained normal throughout gestation without evidence of fetal bradycardia, arrhythmia, or structural abnormalities. Delivery at 38 weeks 5 days' gestation resulted in a healthy female neonate. This case illustrates successful use of off-label ivabradine in pregnancy with reassuring maternal-fetal outcomes under close obstetric-cardiology supervision.},
}
@article {pmid42055743,
year = {2026},
author = {Grach, SL and Seltzer, J and Mueller, MR and Aakre, CA and Natividad, LT and Lawson, DK and Ganesh, R and Hurt, RT},
title = {Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.},
journal = {Annals of family medicine},
volume = {},
number = {},
pages = {},
doi = {10.1370/afm.250266},
pmid = {42055743},
issn = {1544-1717},
abstract = {PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem neurologic disease characterized by profound fatigue and decreased functional capacity, postexertional malaise, and unrefreshing sleep, along with cognitive impairment and/or orthostatic intolerance. Its prevalence has risen exponentially with the COVID-19 pandemic. Pharmacologic therapies have been used successfully by ME/CFS specialists but may be underused by the general medical field.<br><br>METHODS: To assess this potential practice gap, we retrospectively analyzed the records of 571 patients with an ME/CFS diagnosis referred to our ME/CFS specialty clinic in Minnesota during 2018-2022. We ascertained medications that had already been tried at the time of consultation and also ascertained supplement use.<br><br>RESULTS: With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B12 and B complex, and fish oil.<br><br>CONCLUSION: Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.},
}
@article {pmid42056279,
year = {2026},
author = {Faghy, MA and Wüst, RCI and Altmann, DM and Ashton, RE and McMullen, SB and Duncan, R and Ewing, AG and Hausmann, E and Gupta, S and Hornig, M and Joffe, D and Kane, B and Khan, MA and Natt, M and Owen, R and Putrino, D and Skipper, L and Taylor, C and Thomas, C and Tuller, D and Beckman, D and Kruger, A and Pretorius, E},
title = {Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {42056279},
issn = {2730-664X},
abstract = {BACKGROUND: Viral and infectious illnesses can exert profound and enduring effects on population health and well-being. In the aftermath of SARS-CoV-2 infection, post-acute sequelae, collectively referred to as Long COVID, have emerged as a major global health challenge, affecting more than 400 million people and contributing to estimated annual economic costs exceeding $1 trillion.<br><br>SCOPE OF THE REVIEW: Long COVID encompasses a wide and heterogeneous spectrum of debilitating symptoms, including cognitive dysfunction, sleep disturbances, severe fatigue, and post-exertional malaise. Despite its substantial burden, fundamental uncertainties remain regarding its underlying pathophysiology, the development of robust diagnostic criteria, and the identification of effective therapeutic options.<br><br>KEY INSIGHTS: This review synthesises current evidence on the biological mechanisms thought to contribute to Long COVID, spanning immune dysregulation, viral persistence, autonomic dysfunction, microvascular pathology, and other emerging hypotheses. We examine advances and limitations in contemporary diagnostic approaches and critically appraise existing treatment strategies, highlighting inconsistencies and gaps that hinder clinical consensus.<br><br>IMPLICATIONS: By integrating interdisciplinary insights, this review underscores the urgent need for mechanistic clarity, validated diagnostic frameworks, and rigorously evaluated treatment pathways. Addressing these gaps will be essential to developing effective, evidence-based management strategies and mitigating the long-term impact of Long COVID on global health.},
}
@article {pmid42046713,
year = {2026},
author = {Wu, KK and Deng, JS and Jiang, PL and Huang, CL and Tung, TH and Zhu, JS},
title = {Prevalence and influencing factors of long COVID brain fog among college students: a cross-sectional study in Taizhou, China.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e21026},
pmid = {42046713},
issn = {2167-8359},
mesh = {Humans ; Cross-Sectional Studies ; China/epidemiology ; *COVID-19/epidemiology/complications ; Male ; Female ; *Students/statistics &amp; numerical data/psychology ; Prevalence ; Young Adult ; Universities ; SARS-CoV-2 ; Adult ; Surveys and Questionnaires ; Adolescent ; Risk Factors ; },
abstract = {BACKGROUND: Long COVID following SARS-CoV-2 infection is a public health concern. Brain fog, a symptom of long COVID, has an impact on patients' daily lives and health. However, studies on the effects of COVID on college students are limited.<br><br>METHODS: This cross-sectional study included students from two tertiary institutions in Taizhou, China. Data were collected using WeChat-based electronic questionnaires on the Wen-Juan-Xing survey platform from July 20, 2023 to August 7, 2023. Chi-square analyses and binary logistic regression were used to evaluate the factors contributing to brain fog.<br><br>RESULTS: A total of 1,071 students participated in the survey. Of these 1,071 students, 13.7% (147/1,071) reported experiencing long COVID, of whom 27.2% (40/147) reported symptoms of brain fog. Significant associations with brain fog were observed for the following factors: age (> 20 vs. &#x2264; 20 years, odds ratio (OR) = 4.360, 95% confidence interval (CI) [1.620-11.740]), clinical classification of COVID-19 (OR = 2.940, 95% CI [1.230-7.010]), and a decreased sense of smell and taste (OR = 5.110, 95% CI [1.240-21.110]).<br><br>CONCLUSIONS: This study highlights the significant prevalence of long COVID brain fog among college students and identifies key associated factors, underscoring the need for specific, focused interventions and support for affected individuals.},
}
@article {pmid42046721,
year = {2026},
author = {Deng, M and Wang, Y},
title = {Ocular Symptoms in Long COVID: A Cross-Sectional Study [Letter].},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {616430},
pmid = {42046721},
issn = {1177-5467},
}
@article {pmid42040088,
year = {2026},
author = {Onik, G},
title = {A health resort-based intervention reduces insomnia with minimal changes in quality of life in COVID-19 survivors and non-COVID-19 controls.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1803380},
pmid = {42040088},
issn = {2296-2565},
mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy ; *Quality of Life ; *COVID-19/complications/psychology ; Male ; Female ; Middle Aged ; *Health Resorts ; Adult ; *Survivors/psychology/statistics &amp; numerical data ; Aged ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Persistent post-COVID-19 symptoms, especially insomnia, are common and markedly impair quality of life. While some patients improve over time, many experience long-lasting complaints. Health resort treatment has shown potential benefits in long COVID, but its effects on sleep and quality of life remain unclear. This study aimed to evaluate the impact of comprehensive health resort treatment on insomnia and quality of life in post-COVID-19 individuals and to compare outcomes with those without prior SARS-CoV-2 infection.<br><br>METHODS: A total of 101 participants, including 30 post-COVID-19 individuals, underwent comprehensive health resort treatment. Propensity score matching was used to compare post-COVID-19 and non-COVID groups. Insomnia and health-related quality of life were assessed using the Athens Insomnia Scale and EQ-5D-5L, respectively, before and after the sanatorium stay.<br><br>RESULTS: The Athens Insomnia Score significantly decreased in post-COVID-19 individuals following sanatorium treatment (6.24 &#xb1; 5.93 vs. 3.97 &#xb1; 4.19 points; p = 0.0005). The EQ index did not change significantly after treatment (p = 0.08). Overall health status, assessed using the visual analog scale (VAS), significantly improved in individuals with a history of COVID-19 (76.03 &#xb1; 12.70 vs. 88.45 &#xb1; 7.80 points; p < 0.0001). Treatment effectiveness did not differ significantly between the patient groups.<br><br>CONCLUSIONS: Comprehensive health resort treatments may improve insomnia and self-reported health in COVID-19 survivors. Effects on overall quality of life appear limited, and outcomes are similar to those in individuals without prior COVID-19. Further research is needed to clarify the clinical utility of this approach.},
}
@article {pmid42040552,
year = {2026},
author = {Srinivasan, M and Joseph, PV},
title = {A hypothesis connecting dysgeusia due to defects in ATP-P2X3 signaling and fatigue in myalgic encephalomyelitis/chronic fatigue syndrome: lessons learned from long-COVID.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1808646},
pmid = {42040552},
issn = {2296-858X},
abstract = {Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a neuroimmune disease characterized by debilitating post-exertional malaise (PEM), brain-fog/cognitive problems, and dysregulation of the autonomic nervous system. Currently, there are no objective biomarkers for ME/CFS despite decades of research. Here, we compile evidence from literature that supports taste dysfunction, particularly alterations of taste perception mediated by Type II taste receptor cells, may be a critical underrecognized feature of ME/CFS. The impetus is drawn from the emerging evidence of clinicopathological similarities between long-COVID and ME/CFS. We discuss in parallel the mechanisms of cellular metabolism, inflammation, vascular dysfunction, and autonomic dysregulation in ME/CFS and long-COVID pathophysiology. We postulate that mechanistically, dysregulation of ATP signaling through P2X2/P2X3 purinergic receptors underlies both gustatory impairment and core ME/CFS symptoms. Adopting information from the NIH-RECOVER shared resources, we present evidence that suggests chemosensory dysfunction as a potential indicator of progression/severity of PEM. We discuss standardized taste testing as a non-invasive screening tool complementary to molecular biomarkers for ME/CFS. Notwithstanding, we acknowledge the limitations, confounding and contributing factors such as medications and deficiencies that may exacerbate or independently cause taste-related symptoms in ME/CFS. In conclusion, we present a compelling case for the multi-factorial role of taste dysfunction in ME/CFS and suggest specific research priorities for investigating the relationship between chemosensory function and post-viral chronic illness.},
}
@article {pmid42041273,
year = {2026},
author = {Silveira, JM and Nakaishi, APM and da Silva, MG and Dos Santos, DO and Gastaldi, AC},
title = {Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis.},
journal = {Advances in respiratory medicine},
volume = {94},
number = {2},
pages = {},
doi = {10.3390/arm94020025},
pmid = {42041273},
issn = {2543-6031},
mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; *Exercise Therapy/methods ; Quality of Life ; Exercise Tolerance ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; },
abstract = {Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69-63.75) and 30″SST (MD: 4.68, 95% CI 3.59-5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02-13.05) and mental QoL (MD: 6.60, 95% CI 2.01-11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.},
}
@article {pmid42041818,
year = {2026},
author = {Moore, AL and Jedlicka, EJ and Patterson, JC and Ledbetter, CR},
title = {LearningRx Cognitive Training for Workplace Self-Efficacy in Adults with Post-COVID-19 Brain Fog: A Mixed-Methods Pilot Study.},
journal = {Brain sciences},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/brainsci16040410},
pmid = {42041818},
issn = {2076-3425},
support = {Louisiana State University Health Sciences Center Shreveport Research Council Intramural Grants Program Center for Brain Health (CBH) Grant-in-Aid Award.//Louisiana State University/ ; },
abstract = {BACKGROUND/OBJECTIVES: Cognitive dysfunction, or "brain fog", following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to post-COVID-19 brain fog.<br><br>METHODS: Nine adults with post-COVID-19 cognitive dysfunction participated in this single arm pilot trial of a severity-adaptive cognitive training program. The participants completed 45-90 h of clinician-delivered cognitive training exercises delivered remotely in 60- to 90-min sessions, two or three times per week. The primary outcome measure was overall workplace self-efficacy with subskills of perceived workplace functioning, perception of cognitive functioning, and perception of home functioning assessed through pre and post surveys and qualitative interviews. The secondary outcome was cognitive function operationalized by an IQ score administered before and after the intervention.<br><br>RESULTS: The participants achieved significant improvements in workplace self-efficacy and cognition following cognitive training. The main qualitative themes of self-reported improvements were in executive function, health and energy, daily living activities, productivity, and socioemotional functioning. A cross-case synthesis of pre-intervention struggles, and post-intervention improvements revealed subthemes at work or school in cognitive processing and comprehension, memory, executive function, fatigue, emotional distress, confidence in work or academics, and work/academic performance impairment. As a group, the mean gain in IQ score was 10.5 points.<br><br>CONCLUSIONS: This study adds to the growing body of literature examining the possibility of using cognitive rehabilitation for post-COVID-19 cognitive dysfunction impacting workplace self-efficacy and work functioning.},
}
@article {pmid42043247,
year = {2026},
author = {Mahajan, S and Mahajan, S and Kaushik, N},
title = {Integrative Insights into the Immunopathogenesis and Organ-Specific Immunological Mechanisms of Long COVID: A Narrative Review.},
journal = {Viruses},
volume = {18},
number = {4},
pages = {},
doi = {10.3390/v18040458},
pmid = {42043247},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/immunology/pathology/complications/virology ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Adaptive Immunity ; Organ Specificity ; Autoimmunity ; },
abstract = {Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum is heterogeneous, involving respiratory, cardiovascular, neurological, renal, gastrointestinal, and endocrine systems, thereby posing substantial diagnostic and therapeutic challenges. Despite extensive investigation, the precise immunopathogenic mechanisms underlying LC remain incompletely defined. Accumulating evidence suggests that LC is driven by a multifactorial interplay of persistent viral antigen reservoirs, chronic immune activation, dysregulated innate and adaptive immune responses, autoimmunity, endothelial dysfunction, microvascular injury, and aberrant tissue repair. These systemic immune perturbations manifest variably across different organs, contributing to the diverse clinical phenotypes observed. However, mechanistic clarity is hindered by heterogeneity in study designs, limited longitudinal data, and the absence of standardized immunological profiling. This narrative review provides integrative insights into the immunopathogenesis of LC, synthesizing current evidence on systemic immune dysregulation and organ-specific immunological mechanisms. A conceptual framework is proposed to facilitate a structured understanding of this complex syndrome and to guide future research toward targeted immunomodulatory strategies.},
}
@article {pmid42043604,
year = {2026},
author = {Camara, B and Buonsenso, D},
title = {Response to letter: Methodological considerations for interpreting a scoping review of pediatric long COVID biomarkers.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
doi = {10.1007/s00431-026-06992-6},
pmid = {42043604},
issn = {1432-1076},
}
@article {pmid42043629,
year = {2026},
author = {Selvakumar, JP and Wyller, VBB},
title = {Methodological considerations for interpreting a scoping review of pediatric long COVID biomarkers.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
pmid = {42043629},
issn = {1432-1076},
}
@article {pmid42043742,
year = {2026},
author = {Tomaskovic, A and Weber, V and Ochmann, DT and Hillen, B and Neuberger, EWI and Brahmer, A and Lachtermann, E and Lieb, K and Simon, P},
title = {Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.},
journal = {Sports medicine - open},
volume = {12},
number = {1},
pages = {},
pmid = {42043742},
issn = {2199-1170},
abstract = {BACKGROUND: Patients severely affected by post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience long-term work incapacity, contributing to a growing economic burden. Organ-centered clinical diagnostics frequently fail to explain their work disability.<br><br>OBJECTIVES: We aimed to objectively assess physical work ability using cardiopulmonary exercise testing (CPET) in a cohort of long-standing and severely affected PCC patients. We hypothesized: (1) patients with ME/CFS exhibit lower peak oxygen uptake (VO&#x2082;peak [mL/min/kg]) and peak power output (PPO [W/kg]) than those without; (2) most patients demonstrate objective work disability, closely aligned with subjective perception of disability; (3) oxygen pulse (O2 pulse [mL/bpm]) is reduced in ME/CFS, independent of comorbidity.<br><br>METHODS: The study was conducted in the Department of Sports Medicine, Prevention and Rehabilitation at Johannes Gutenberg-University Mainz (Mainz, Germany). Between July 31, 2023, and March 31, 2025, a total of 92 PCC patients with suspected occupational disease underwent symptom-limited CPET and completed the Canadian Consensus Criteria, Bell Disability Scale (Bell-Score), and DePaul Symptom Questionnaire (Post-Exertional Malaise) Short Form (DSQ-PEM).<br><br>RESULTS: Nearly half of the patients (49%) met ME/CFS criteria and 79% screened positive on the DSQ-PEM. ME/CFS patients showed significantly lower VO&#x2082;peak (13.0&#x2009;&#xb1;&#x2009;3.1 vs. 15.4&#x2009;&#xb1;&#x2009;4.9, p&#x2009;=&#x2009;0.012), PPO (0.9&#x2009;&#xb1;&#x2009;0.3 vs. 1.1&#x2009;&#xb1;&#x2009;0.5, p&#x2009;=&#x2009;0.014), and O&#x2082; pulse (7.7&#x2009;&#xb1;&#x2009;2.0 vs. 8.5&#x2009;&#xb1;&#x2009;1.9, p&#x2009;=&#x2009;0.047) compared to those without ME/CFS. Overall, 66% of patients met objective thresholds for work disability (VO&#x2082;peak&#x2009;<&#x2009;15&#xa0;mL/min/kg or PPO&#x2009;<&#x2009;1 W/kg). Forty-five patients (51%) had a Bell-Score&#x2009;&#x2264;&#x2009;30 and 82% from those had VO&#x2082;peak&#x2009;<&#x2009;15&#x202f;and/or PPO&#x2009;<&#x2009;1. VO&#x2082;peak and PPO significantly correlated with Bell-Score (r&#x2009;=&#x2009;0.3, p&#x2009;=&#x2009;0.005 and r&#x2009;=&#x2009;0.3, p&#x2009;=&#x2009;0.003) and were the lowest among patients on medical sick leave (13.3&#x2009;&#xb1;&#x2009;3.3 and 0.9&#x2009;&#xb1;&#x2009;0.3), compared to those in occupational reintegration (16.0&#x2009;&#xb1;&#x2009;3.9, p&#x2009;=&#x2009;0.04 and 1.2&#x2009;&#xb1;&#x2009;0.5, p&#x2009;=&#x2009;0.024) or currently working (18.0&#x2009;&#xb1;&#x2009;7.1, p&#x2009;=&#x2009;0.036 and 1.2&#x2009;&#xb1;&#x2009;0.5, p&#x2009;=&#x2009;0.015).<br><br>CONCLUSIONS: Severely affected PCC patients exhibit objective work disability, particularly those with ME/CFS. VO&#x2082;peak and PPO are associated with subjective disability and occupational status. Therefore, early integration of CPET into clinical and occupational evaluations can inform individualized therapy planning and return-to-work decisions. Trial registration DRKS, DRKS00032394. Registered 28 July 2023, https://drks.de/search/de/trial/DRKS00032394.},
}
@article {pmid42045916,
year = {2026},
author = {Li, S and Zhao, H and Zhang, M and Yuan, T and Li, X and Shen, Z and Qin, C and Li, Y and Pan, M},
title = {Long-term health outcomes in elderly COPD patients with long COVID: a 2-year prospective cohort study.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03689-0},
pmid = {42045916},
issn = {1465-993X},
}
@article {pmid42035205,
year = {2026},
author = {Yuan, MQ and Pan, YF and Zhang, ZY and Wu, YX and Zhu, KD and Wang, ZR and Zhang, ZY and Xiong, JQ and Xu, Z and Huang, L and Wang, FS and Shi, L},
title = {Therapeutic potential of mesenchymal stromal cells in COVID-19: a meta-analysis of clinical trials conducted since the pandemic onset.},
journal = {Stem cell research &amp; therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-05020-6},
pmid = {42035205},
issn = {1757-6512},
support = {No. 2022YFA1105604//National Key Research and Development Program of China/ ; },
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID.<br><br>METHODS: We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n&#x2009;=&#x2009;1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger's test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively.<br><br>RESULTS: MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR&#x2009;=&#x2009;0.74, 95% CI 0.55-0.99), with low heterogeneity (I[2]&#x2009;=&#x2009;2.8%, P&#x2009;=0.422[Q-test]) and no publication bias. The quality of evidence was moderate (according to the GRADE assessment). The subgroup analysis revealed a significant survival benefit in severe/critical patients (OR&#x2009;=&#x2009;0.73, 95% CI 0.54-0.98) but not in studies that included moderate cases (OR&#x2009;=&#x2009;0.91, 95% CI 0.23-3.65). No significant heterogeneity was found across study designs, administration routes, or dosing frequencies, which confirmed the robustness of the primary findings while indicating insufficient evidence to determine the optimal regimen. The secondary outcomes suggested improvements in clinical recovery, pulmonary function, and pro-/anti-inflammatory cytokine balance in patients that received MSC therapy. Limited studies with long-term follow-up indicated potential benefits for Long-COVID outcomes (e.g., fatigue, quality of life, residual CT abnormalities, and exercise tolerance). No significant differences were observed in AEs or SAEs post-MSC infusion, which suggested that MSC therapy was well tolerated.<br><br>CONCLUSION: This meta-analysis indicated that MSC therapy may reduce mortality in patients with severe or critical COVID-19, demonstrating a favorable safety profile and potential benefits for Long-COVID and other viral pneumonias. Further large-scale, rigorous RCTs and mechanistic studies are warranted to strengthen the evidence base and standardize MSC administration regimens (source, dosing, frequency, and intervals) for managing COVID-19, Long-COVID, and other viral pneumonias.},
}
@article {pmid39668387,
year = {2025},
author = {Savith, A and Meah, A and Murthy, RSS and Phal, NB},
title = {Long-term Health Implications of Coronavirus Disease 2019: A Prospective Study on Post-coronavirus Disease 2019 Symptoms.},
journal = {Annals of African medicine},
volume = {24},
number = {1},
pages = {167-172},
pmid = {39668387},
issn = {0975-5764},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology/diagnosis ; Prospective Studies ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Severity of Illness Index ; Aged ; Post-Acute COVID-19 Syndrome ; Hospitalization ; Prevalence ; Fatigue/epidemiology ; Dyspnea/epidemiology ; },
abstract = {CONTEXT: Patients recovering from coronavirus disease 2019 (COVID-19) infection continue to have some persistent symptoms or develop new symptoms, resulting in impairment of everyday activities beyond the initial acute period. The current study was undertaken to understand the long term health implications of covid 19 and to analyse the correlation of post covid symptoms with the severity of infection and inflammatory markers at the time of hospitalisation.<br><br>AIMS: (1) To estimate the prevalence of post covid symptoms at the end of 1 month,3 months and 12 months after discharge, (2) To correlate post covid symptoms with the severity of infection and inflammatory markers at the time of hospitalisation.<br><br>SETTINGS AND DESIGN: The study design was a cross-sectional study.<br><br>SUBJECTS AND METHODS: A prospective observational study was done on 150 COVID-19 reverse transcription-polymerase chain reaction-positive patients aged 18 years and above recovering from acute infection discharged from Vydehi Institute of Medical Sciences and Research Centre. All the patients were followed up for 1 year, during which telephonic interviews were conducted, and a systematic enquiry was made regarding post-COVID-19 symptoms.<br><br>STATISTICAL ANALYSIS USED: Data were entered in MS Excel and analyzed in SPSS V25. Descriptive statistics are represented with percentages, mean with standard deviation, or median with interquartile range depending on the nature of the data. The Kolmogorov-Smirnov test was applied to find normality. The Chi-square test, Independent t -test, or Mann-Whitney U -test were calculated depending on normality; P < 0.05 was considered statistically significant.<br><br>RESULTS: A total of 150 COVID-19-positive patients discharged from the hospital were included in the study. Sixty-seven percent of patients had symptoms at 1 month, 39% at 3 months, and 31% of patients persisted to have symptoms at 1 year. The most common symptoms at 1 year were fatigue (5%), breathlessness (5%), and insomnia (5%). No statistically significant correlation was found with the severity of infection, inflammatory markers, and other variables.<br><br>CONCLUSIONS: Approximately one-third of patients who recover from acute COVID-19 infection may continue to have post-COVID-19 symptoms at 1 year after infection. Fatigue is the most common post-COVID-19 symptom. Post-COVID-19 symptoms can affect COVID-19 survivors regardless of the severity of the infection.},
}
@article {pmid42026739,
year = {2026},
author = {Thomas, C and Ashton, RE and Owen, R and McNeil-Angopa, E and Carr, J and Bewick, T and Faghy, MA},
title = {Impaired peripheral oxygen delivery during submaximal exercise in adults with long COVID.},
journal = {Physiological reports},
volume = {14},
number = {8},
pages = {e70873},
doi = {10.14814/phy2.70873},
pmid = {42026739},
issn = {2051-817X},
support = {IN-UK-983-6080//Gilead Sciences (Gilead)/ ; },
mesh = {Humans ; *COVID-19/physiopathology/metabolism/complications ; Male ; Female ; Middle Aged ; *Muscle, Skeletal/metabolism/physiopathology ; *Exercise/physiology ; Exercise Test ; Adult ; *Oxygen Consumption ; *Oxygen/metabolism ; Spectroscopy, Near-Infrared ; SARS-CoV-2 ; },
abstract = {Long COVID (LC) is a multisystem condition that is linked to distinct pathologies including viral persistence, immunological dysfunction, endothelial damage, and mitochondrial dysfunction. To date, limited research has assessed peripheral tissue hypoxia to better understand LC symptom exacerbation. Forty-six people with LC and 10 controls (CON) completed two submaximal cardiopulmonary exercise tests (CPETs), separated by 24-h. Near-infrared spectroscopy (NIRS)-derived signals from the left gastrocnemius muscle were continuously monitored before, during, and after 2-day incremental CPET. CPET outcomes demonstrated impaired physical function on day 2 compared with day 1 for the LC cohort at rest and VT1. LC tissue saturation index (TSI%) remained elevated above rest for a shorter duration of exercise compared to CON on day 1 (2nd minute vs. 5th minute). On day 2, this response worsened for LC (Rest vs. 1st exercise minute: 63 ± 5% vs. 65 ± 5%; p < 0.05); meanwhile, CON exhibited sustained TSI% elevation throughout exercise above rest (Rest vs. 12th exercise minute: 62 ± 5% vs. 67 ± 4%; p < 0.05). LC TSI% remained elevated above rest for a shorter duration of exercise compared to CON, worsening for LC on day 2. LC showed rapid normalization of TSI%, suggesting impaired muscle oxygenation and recovery during repeated exercise.},
}
@article {pmid42028736,
year = {2026},
author = {Samet, M and Aghaei-Meybodi, FA and Hosseini, S and Meidany, A and Fateh, A},
title = {Lung autopsy findings in 44 COVID-19 deceased patients:pathological and radiological insights.},
journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace},
volume = {},
number = {},
pages = {},
doi = {10.4081/monaldi.2026.3412},
pmid = {42028736},
issn = {2532-5264},
abstract = {This study presents a detailed histopathological analysis of lung tissue from 44 deceased COVID19 patients, aiming to elucidate the mechanisms driving severe disease progression. Postmortem biopsies were systematically examined, revealing diffuse alveolar damage in 95.5% of cases, predominantly in the acute/exudative phase. Characteristic features included extensive hyaline membrane formation, alveolar septal thickening, fibrin deposition, and red blood cell extravasation. Notably, advanced fibrosis, indicative of ongoing tissue remodeling, was observed in 86.4% of cases, highlighting the chronic pathological impact of the disease. Patient demographics showed a predominance of older males with comorbidities such as hypertension and diabetes, aligning with known high-risk profiles. The methodology involved meticulous autopsy procedures and standardized histopathological assessments to ensure the reliability of findings. This study provides key insight into histological changes in the lungs of COVID-19 patients, helping to clarify the disease's progression. It provides valuable insights that may contribute to a better understanding of long COVID and the potential long-term pulmonary complications in these patients. These findings may ultimately support improved management approaches and therapeutic strategies for COVID-19 care.},
}
@article {pmid42028925,
year = {2026},
author = {Silva, LI and Gonzalez-Zambrano, CM and Ferreira, VCMP and Corrêa, FC and Dias-Melicio, LA},
title = {MicroRNAs in Acute COVID-19 and Long COVID: Dysregulation, Pathogenic Roles, and Clinical Implications.},
journal = {Journal of immunology research},
volume = {2026},
number = {1},
pages = {e5862241},
doi = {10.1155/jimr/5862241},
pmid = {42028925},
issn = {2314-7156},
support = {001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; },
mesh = {Humans ; *COVID-19/genetics/immunology/virology/pathology ; *MicroRNAs/genetics ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Extracellular Vesicles ; Gene Expression Regulation ; Biomarkers ; Inflammation ; },
abstract = {MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression with central roles in immune responses, inflammation, and viral pathogenesis. Increasing evidence indicates that severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection induces marked dysregulation of host and viral miRNAs (v-miRNAs), contributing to disease severity during acute COVID-19 and to the persistent manifestations observed in long COVID (LC). This narrative review critically synthesizes current evidence on miRNA dysregulation across the acute and post-acute phases of COVID-19, highlighting their pathogenic roles, clinical relevance, and existing knowledge gaps. During acute infection, altered miRNA profiles-including those associated with immune activation, endothelial dysfunction, and immunothrombosis-reflect both host responses and viral strategies of immune modulation, including miRNAs carried by extracellular vesicles (EVs) and SARS-CoV-2-derived v-miRNAs. In LC, emerging data suggest that persistent miRNA alterations are associated with unresolved inflammation, pulmonary dysfunction, neurological symptoms, and vascular injury, although available studies remain limited and heterogeneous. Overall, miRNAs represent promising biomarkers and potential therapeutic targets in COVID-19; however, robust longitudinal and mechanistic studies are urgently needed to clarify their causal roles and translational utility in post-acute disease.},
}
@article {pmid42029517,
year = {2026},
author = {Couto, NMS and Bernal, JVM and Facioli, TP and Dos Santos, D and de Souza, HCD},
title = {The Severity of COVID-19 Is Associated with Greater Impairment of Cardiac Autonomic Modulation-Physical Training as a Countermeasure.},
journal = {Journal of functional morphology and kinesiology},
volume = {11},
number = {2},
pages = {},
doi = {10.3390/jfmk11020149},
pmid = {42029517},
issn = {2411-5142},
support = {2023/17422-7//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 001//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; },
abstract = {Background: COVID-19 has been associated with persistent impairments in autonomic modulation of heart rate variability (HRV). However, whether disease severity during the acute phase influences the magnitude of these impairments remains insufficiently explored. In turn, aerobic physical training (APT) has been proposed as a countermeasure to autonomic dysfunction of HRV in different conditions, although its effects in individuals with COVID-19 are not yet well established. To address these gaps, this study investigated the consequences of COVID-19 on autonomic modulation of HRV according to disease severity and evaluated the effects of APT on this parameter. Methods: One hundred and sixteen individuals (58 men and 58 women) aged between 30 and 55 years were included, allocated into three groups according to the severity of the disease in the acute phase: Mild group (n = 38, mean age: 48 ± 7 years); Moderate group (n = 52, mean age: 43 ± 5 years); and Severe group (n = 26, mean age: 45 ± 6 years). All groups had anthropometric and hemodynamic parameters evaluated before and after the 16-week APT period, as well as parameters of autonomic modulation of HRV analyzed using linear (time and frequency domain) and non-linear (symbolic analysis) methods obtained from R-R interval (RRi) recordings in the supine position for 30 min. Results: Initially, all groups presented similar anthropometric and hemodynamic values. In contrast, the Moderate and Severe groups presented lower values for standard deviation of normal RRi (SDNN; Moderate: 38 ± 14 ms; Severe: 33 ± 12 ms vs. Mild: 55 ± 28 ms; p < 0.001), root mean square difference between adjacent normal RRi (RMSSD; Moderate: 28 ± 13 ms; Severe: 22 ± 7 ms vs. Mild: 47 ± 38 ms; p < 0.001), total variance (Moderate: 203 ± 127 ms[2]; Severe: 303 ± 157 ms[2] vs. Mild: 526 ± 347 ms[2]; p < 0.001), and high-frequency (HF) oscillations in absolute units (Moderate: 259 ± 270 ms[2]; Severe: 153 ± 74 ms[2] vs. Mild: 438 ± 421 ms[2]; p < 0.001), both compared to the Mild group. In turn, the Severe group, when compared to the other groups, also presented lower HF oscillations (Severe: 29 ± 12 nu vs. Mild: 44 ± 17 nu and Moderate: 42 ± 17 nu; p < 0.001) and higher low-frequency (LF) oscillations (Severe: 71 ± 12 nu vs. Mild: 60 ± 17 nu and Moderate: 58 ± 17 nu; p < 0.001), but in normalized units. After the 16-week APT, all groups showed increases in HF oscillations (Mild: -206 ms[2] and -19.12 nu; Moderate: -236 ms[2] and -26.7 nu; Severe: -211 ms[2] and -31.0 nu; p < 0.001) and reductions in LF oscillations (Mild: 198 ms[2] and 19.01 nu; Moderate: 98 ms[2] and 26.7 nu; Severe: 218 ms[2] and 31.1 nu; p < 0.001), both in absolute and normalized units. In this case, there were no further differences in LF and HF oscillations between the groups. Conclusions: Individuals who had COVID-19 and developed moderate to severe cases showed greater impairments in the autonomic modulation of HRV, characterized by increased sympathetic autonomic modulation and reduced vagal modulation. In turn, APT as a countermeasure appears to increase vagal autonomic modulation and reduce sympathetic autonomic modulation of HRV, regardless of the previous severity of COVID-19.},
}
@article {pmid42021271,
year = {2026},
author = {Sommen, SL and Segtnan, S and Selvakumar, J and Havdal, LB and Stiansen-Sonerud, T and Gjerstad, J and Mjaaland, S and Nygaard, UC and Wyller, VBB and Mukherjee, R and Berven, LL},
title = {Long COVID: Deep single-cell immunophenotyping and machine learning reveal a general signature for fatigue.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08149-3},
pmid = {42021271},
issn = {1479-5876},
}
@article {pmid42022303,
year = {2025},
author = {Tabarsi, P and Mohamadnia, A and Shahabinejad, P and Haseli, S and Askari, E and Bahrami, N and Shafaghi, S and Hajimoradi, M},
title = {Long COVID in Patients with Multiple Sclerosis Treated with Rituximab: A Report of Two Cases.},
journal = {Tanaffos},
volume = {24},
number = {1},
pages = {106-110},
pmid = {42022303},
issn = {1735-0344},
abstract = {COVID-19 symptoms may persist for more than 12 weeks in some infected patients, a condition described as long COVID-19 in these cases. These patients have symptoms attributed to impairment of multiple organs. Scientists have discovered the lengthy COVID-19 etiology, risk factors, and treatments. It has been observed that immunosuppression may prolong COVID-19 symptoms. Patients with multiple sclerosis (pwMS) are generally treated with disease-modifying treatments, which suppress the immune system and predispose patients to infections like COVID-19. Also, these drugs may increase not only the morbidity and mortality of infection but also the risk of developing long COVID-19 in these patients. We have described two cases of multiple sclerosis patients who were diagnosed with long COVID-19. Both patients were under treatment with rituximab, so we discussed treatment choices and strategies for pwMS patients under rituximab who had symptoms of long COVID. Our data would further add to the information on managing long COVID-19 in pwMS under treatment with rituximab.},
}
@article {pmid42022621,
year = {2026},
author = {Obeagu, EI},
title = {Taming the Cytokine Storm: Therapeutic Strategies for Post-Acute Sequelae of SARS-CoV-2 Infection.},
journal = {Health science reports},
volume = {9},
number = {3},
pages = {e72174},
pmid = {42022621},
issn = {2398-8835},
abstract = {BACKGROUND AND AIM: Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID, has emerged as a significant global health concern, marked by persistent symptoms and chronic inflammation following recovery from acute COVID-19. A central driver of PASC pathogenesis is the sustained cytokine storm-an exaggerated and prolonged pro-inflammatory response that leads to ongoing tissue injury and multisystem dysfunction. This review aims to synthesize current knowledge on cytokine dysregulation in PASC and evaluate emerging therapeutic strategies targeting these immunopathological mechanisms.<br><br>METHODS: A narrative review methodology was employed, drawing from recent peer-reviewed publications, clinical trial databases, and immunological studies published between 2020 and 2025. Articles focusing on cytokine profiles in PASC, immune reprogramming, and immunomodulatory therapies were included. Mechanistic studies, biomarker research, and translational trials involving corticosteroids, cytokine inhibitors, Janus kinase (JAK) inhibitors, and novel biologics were critically analyzed.<br><br>RESULTS: The literature reveals that elevated levels of IL-6, IL-1&#x3b2;, TNF-&#x3b1;, and IFN-&#x3b3; persist in a subset of PASC patients, contributing to chronic systemic and organ-specific inflammation. Emerging therapies-including IL-6 and IL-1 receptor antagonists, JAK inhibitors, and CNS-penetrant anti-inflammatory agents-demonstrate promise in modulating cytokine storms and improving clinical outcomes. Recent insights into cytokine profiling, trained immunity, and neuroimmune crosstalk suggest potential for precision-based interventions tailored to distinct inflammatory phenotypes in PASC.<br><br>CONCLUSION: Persistent cytokine dysregulation underlies the pathophysiology of PASC and offers actionable targets for therapeutic intervention. Immunomodulatory strategies, when guided by biomarker profiling and systems biology approaches, hold promise for mitigating long-term complications of COVID-19. Future research should prioritize personalized treatment algorithms to address the heterogeneity of PASC and enhance patient recovery.},
}
@article {pmid42026280,
year = {2026},
author = {Stanley, HB and Bensafi, M},
title = {The characteristics of chemosensory losses in the symptomatology of long-COVID.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {},
number = {},
pages = {},
pmid = {42026280},
issn = {1434-4726},
support = {964529//Horizon 2020 Framework Programme/ ; Human Chemosensation IRP project//CNRS/ ; },
}
@article {pmid42002663,
year = {2026},
author = {Stervbo, U and Anft, M and Paniskaki, K and Blazquez-Navarro, A and Doevelaar, A and Skrzypczyk, S and Kohut, E and Kurek, J and Wehler, P and Kaliszczyk, S and Rosiewicz, K and Seibert, FS and Hölzer, B and Thieme, CJ and Roch, T and Konik, MJ and Berger, MM and Brenner, T and Kölsch, U and Adamzik, M and Schmueck-Henneresse, M and Scheibenbogen, C and Dolff, S and Dittmer, U and Witzke, O and Westhoff, TH and Babel, N},
title = {Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein-Barr virus reactivation.},
journal = {Medical microbiology and immunology},
volume = {215},
number = {1},
pages = {},
pmid = {42002663},
issn = {1432-1831},
abstract = {UNLABELLED: Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked samples, we evaluated the co-occurrence of CMV, EBV, as well as HHV-6A and -6B by qPCR. EBV was found to be reactivated not only in patients with critical or severe COVID-19 (24/33 patients; 72.72%), but also in patients with moderate COVID-19 disease (19/28; 67.86%) at the time of hospital admission. In contrast, HHV-6A was not detected among any patients, whereas CMV and HHV-6B only occurred in low frewuencies (7.1–12.1% and 10.7–15.2%, respectively). In COVID-19 patients with EBV reactivation, the degree of expression of the T-cell co-stimulatory CD28 and co-expression of CD28 and the integrin CD11a was diminished on CD8 T-cells. In contrast, the frequency of CD8 T-cells expressing the proliferative exhaustion marker CD57 increased. Collectively, these data point to an altered activation phenotype of circulating CD8 T cells and that higher replicative senescence is associated with EBV reactivation. The data presented here suggests an alteration in the CD8 T-cell compartment with impaired ability to control the EBV reactivation in COVID patients.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00430-026-00873-3.},
}
@article {pmid42015188,
year = {2026},
author = {Sardell, JM and Das, S and Pearson, M and Kolobkov, D and Malinowski, AR and Fullwood, LM and Sanna, M and Baxter, H and McLellan, K and Natt, M and Lamirel, D and Chowdhury, S and Strivens, MA and Gardner, S},
title = {Identification of novel reproducible combinatorial genetic risk factors for myalgic encephalomyelitis in the DecodeME patient cohort and commonalities with long COVID.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08167-1},
pmid = {42015188},
issn = {1479-5876},
support = {10083274//Innovate UK/ ; },
}
@article {pmid42016647,
year = {2026},
author = {Wetmore, E and Grach, S and Boes, C and Lanzino, G and Kissoon, N},
title = {Long COVID Syndrome and Associated New Daily Persistent Headache (NDPH) Presenting With Crossed Clonus Response.},
journal = {Clinical case reports},
volume = {14},
number = {3},
pages = {e72386},
pmid = {42016647},
issn = {2050-0904},
abstract = {Evaluating patients following a COVID-19 infection with multiple chronic, progressive symptoms can be challenging, but easy to navigate by using the temporal profile obtained from the clinical history, findings from the neurological exam, and screening for red flag symptoms.},
}
@article {pmid42017188,
year = {2026},
author = {Alvarez-Pedrerol, M and Polo-Alonso, S and Ramos, R and Martí-Lluch, R and Pinsach-Abuin, ML and Dégano, IR and Elosua, R and Subirana, I and Hernáez, &#xc1; and Selga, E and Puigdecanet, E and Pruneda-Paz, J and Solà-Richarte, C and Puigmulé, M and Pérez, A and Nogués, X and Masclans, JR and Güerri-Fernández, R and Cubero-Gallego, H and Tizon-Marcos, H and Vaquerizo, B and Brugada, R and Camps-Vilaró, A and Marrugat, J},
title = {Sex Differences in Long COVID Prevalence Over One year After the Acute Phase, and Related Risk Factors. The GINA-COVID Cohort Study.},
journal = {International journal of women's health},
volume = {18},
number = {},
pages = {538491},
pmid = {42017188},
issn = {1179-1411},
abstract = {BACKGROUND: This 1-year cohort study aimed to track long COVID prevalence, identify associated risk factors, and assess its association with hospitalization.<br><br>METHODS: The GINA-COVID cohort study included 2698 COVID-19 patients from Spain, who reported persistent symptoms spontaneously mentioned in an open questionnaire one year after infection. We recorded symptom onset, duration, and recovery rates at 12 months. Hospitalization data were collected from the Catalan Health System. We performed descriptive statistics and logistic regression models stratified by sex to identify factors associated with long COVID, using multiple imputation for missing values and model selection via stepwise regression based on the Akaike Information Criterion.<br><br>RESULTS: Significant sex differences appeared, with females showing a two-fold higher risk of developing long COVID compared to males (OR=1.95; 95% CI, 1.68-2.29). Females reported higher prevalence and a greater number of persistent symptoms, with fatigue being the most common in both sexes (36% in females, 26% in males at 3 months). The recovery rate at 12 months was lower in females (23% vs. 34%, p<0.001). Hypertension emerged as the most significant protective factor for long COVID in females (OR=0.64; 95% CI, 0.48-0.84), whereas COVID-19 severity was the most influential risk factor in males (OR=2.34; 95% CI, 1.79-3.08). Despite these differences, the trajectory of persistent symptoms over time was similar between the sexes. Importantly, long COVID did not increase hospital admissions.<br><br>CONCLUSION: Findings underscore the importance of sex-specific approaches in managing long COVID and suggest further investigation into hypertension's protective role in females and disease severity's impact in males.},
}
@article {pmid42017426,
year = {2026},
author = {Krzyzanowski, MC and Pan, H and Glaze, I and Hwang, S and Williams, D and Engle, M and Waterfield, J and Ives, C and Armson, S and Huggins, W and Hamilton, CM},
title = {The PhenX Toolkit: Long COVID Collection of Standard Protocols.},
journal = {Current protocols},
volume = {6},
number = {4},
pages = {e70317},
doi = {10.1002/cpz1.70317},
pmid = {42017426},
issn = {2691-1299},
support = {/HG/NHGRI NIH HHS/United States ; (U41HG007050)//Genomic Research/ ; (U24HG012556)//Biomedical Knowledgebase/ ; /CD/ODCDC CDC HHS/United States ; /HL/NHLBI NIH HHS/United States ; /NS/NINDS NIH HHS/United States ; /MD/NIMHD NIH HHS/United States ; /CA/NCI NIH HHS/United States ; /DA/NIDA NIH HHS/United States ; //Office of Behavioral and Social Sciences Research/ ; /ES/NIEHS NIH HHS/United States ; //Disaster Research Response (DR2)/ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; *Data Collection/methods ; Crowdsourcing/methods ; },
abstract = {Because of the urgent need to better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission mechanism and clinical outcomes resulting from infection, health organizations and research institutes developed data collection instruments to assess coronavirus disease 2019 (COVID-19) symptoms, treatments, and associated impacts on behaviors and risks, treatment and outcomes, information available, psychosocial and mental health, and socioeconomic effects across demographic groups. The PhenX team developed the COVID-19 Protocol Library to share data collection instruments, methods, and protocols in use by investigators and to reduce proliferation of similar protocols. The Office of Behavioral and Social Sciences Research and the National Human Genome Research Institute sponsored the effort, in collaboration with the NIH Disaster Research Response Program. As the COVID-19 library was being established, crowdsourcing was used to identify key topics related to the pandemic, which formed the basis of the COVID-19 Research Collection, and was released in the PhenX Toolkit. Long COVID continues to have an impact on human health. Long COVID is a chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months, encompassing a variety of symptoms or conditions that may improve, worsen, or be ongoing. Not surprisingly, submissions to the COVID-19 library began to address Long COVID symptoms. After discussions with its Steering Committee, the PhenX team established a collection of Long COVID measurement protocols. Also, there was significant interest in assessing the amount of overlap among all instruments submitted to the COVID-19 library. The intent was to develop a tool that could identify potential for cross-study analyses. The COVID-19 Variable Compare Tool (VCT) integrates all COVID-19 Research Collection protocols and a prioritized subset of instruments from the COVID-19 library. The Long COVID Specialty Collection and the VCT support investigators' needs to combine and analyze data related to COVID-19 prospectively and retrospectively by identifying compatibility with other studies. © 2026 RTI International. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Exploring Long COVID through PhenX Toolkit Specialty Collections and the Variable Compare Tool.},
}
@article {pmid42017829,
year = {2026},
author = {Sun, H and Dang, R and Li, P and Xiao, W and Scott-Sutherland, J and Sassower, KC and Westover, MB and Felsenstein, D and Thomas, RJ and Haack, M and Mullington, JM},
title = {Facility-Measured Sleep Electroencephalographic Microstructures in Long COVID.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag090},
pmid = {42017829},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: Sleep electroencephalographic (EEG) microstructures are related to brain functions, providing a window into the unrefreshing, non-restorative sleep and daytime fatigue symptoms in long COVID (LC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aim to characterize sleep EEG microstructural differences in individuals with LC and age-sex-matched healthy controls (HC), and also ME/CFS, using overnight in-lab facility-measured polysomnography (PSG).<br><br>METHODS: 28 LC and 28 HC participants came from a single-center research study. 19 ME/CFS participants came from a single clinical center. Sleep EEG was processed to extract spectral band powers, spindles, slow oscillations (SO, 0.5-1&#xa0;Hz), spindle-SO coupling, brain age index (BAI), alpha-delta patterns, and infraslow oscillation relative band power (ISO, 0.005-0.03&#xa0;Hz).<br><br>RESULTS: Compared to HC, LC had higher SO power during wake before sleep and REM sleep. In N2 and N3, LC showed a faster within-spindle frequency drop (chirp) and shorter SO peak duration in the frontal region. LC showed widespread, early spindle-SO coupling phase at SO trough for both fast and slow spindles, with early fast spindle-SO coupling associated with worse sleep quality. ME/CFS shared some differences with LC but had higher SO-uncoupled slow spindle densities in frontal and central regions, more alpha-delta patterns in the first half of the night, and widespread elevated ISO power in the slow sigma band (11-13&#xa0;Hz).<br><br>CONCLUSIONS: These findings suggest that LC and ME/CFS are associated with plausibly pathological sleep EEG microstructure changes, illuminating the pathobiology of post-infectious processes on brain activity.CLINICAL TRIAL INFORMATIONTrial 1: Sleep and Inflammatory Resolution Pathway, https://clinicaltrials.gov/study/NCT03377543, NCT03377543.Trial 2: Pain in Long COVID-19: the Role of Sleep, https://clinicaltrials.gov/study/NCT05606211, NCT05606211.},
}
@article {pmid42018978,
year = {2026},
author = {Gesell, D and Lienesch, P and Shi, Y and Strobl, R and Tauscher, M and Gerlach, R and Grill, E and Koller, D},
title = {Care Pathways and Patient Experiences Among Patients With Post COVID-19 Condition: Study Protocol for a Mixed-Methods Study in Germany.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e91976},
doi = {10.2196/91976},
pmid = {42018978},
issn = {1929-0748},
mesh = {Humans ; Germany/epidemiology ; *COVID-19/therapy/complications/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Qualitative Research ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; *Critical Pathways ; Research Design ; Female ; Male ; Focus Groups ; Post-Acute COVID-19 Syndrome ; Pandemics ; },
abstract = {BACKGROUND: The COVID-19 pandemic has a lasting impact on health care utilization, as both the acute infection and post COVID condition (PCC) can lead to increased demand for medical services due to ongoing symptoms.<br><br>OBJECTIVE: The aim of this study is to systematically examine health care utilization among individuals after acute SARS-CoV-2 infection in Bavaria, Germany, with a particular focus on PCC. The study combines claims data analysis with qualitative interviews to improve the understanding of objective care pathways and patients' subjective experiences within the health care system.<br><br>METHODS: The research project 'SOLongCOVID' employs a mixed-methods design consisting of two subprojects: (1) a retrospective cohort study using claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) to analyze care pathways through state sequence analysis, (2) a qualitative study based on semistructured interviews and focus groups with patients with PCC concerning their subjective care experiences. A synthesis process involving a focus group discussion will combine the information from the two subprojects, providing a comprehensive understanding of the care processes of patients with PCC.<br><br>RESULTS: The study was funded by the German Federal Joint Committee Innovation Fund in October 2024. Statutory health insurance claims data cover the period from 2019 to 2022, and qualitative interview data collection is planned from May 2025 to August 2026. As of manuscript submission, study preparation and ethics approvals have been completed, and 14 participants have been recruited for the qualitative interviews. Study findings are anticipated to be published from July 2026 to August 2027.<br><br>CONCLUSIONS: The results are expected to enhance the understanding of existing barriers and challenges and to support evidence-based recommendations for improving care pathways for patients with specific care needs.},
}
@article {pmid42019647,
year = {2026},
author = {Nieuwland, JM and Scaramuzza, A and Bugiani, M and van de Berg, WDJ and Middeldorp, J},
title = {Human brain matters: Navigating the neuropathology of COVID-19.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70101},
doi = {10.1111/bpa.70101},
pmid = {42019647},
issn = {1750-3639},
support = {//European research project NEUROCOV, funded by Horizon Europe (EU)/ ; },
abstract = {Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths worldwide. Although the incidence of severe acute cases has declined, the prevalence of long COVID, also known as post-acute sequelae of COVID-19 (PASC), is rising. The pathological mechanisms underlying severe COVID-19, along with the relationship to neurological disorders and potential risk for neurodegeneration, remain poorly understood. The aim of this narrative review is to summarize neuropathological features described in postmortem human COVID-19 brains (n = 352). Furthermore, analysis of biofluids and neuroimaging from PASC patients underline long-term changes in the proteome and CNS response following the infection. Postmortem brain studies from severe COVID-19 patients highlight disruption of the fluid-brain barriers and vascular dysregulation defined by endothelial inflammation and disruption, hemorrhages, and hypoxic-ischemic damage. Neuroinflammation, including astrogliosis, microglia nodules and infiltration of adaptive immune cells, has been reported in the olfactory bulb, medulla oblongata, midbrain and cerebellum. Neuronal damage was demonstrated in the hippocampus, midbrain and cerebellum in severe COVID-19 and protein aggregation was observed in the midbrain and entorhinal cortex. Neuropathological burden and elevated blood and/or cerebrospinal fluid (CSF) levels of proinflammatory cytokines (e.g. IL-6) and neuro-axonal proteins (e.g. NfL) correlated with severity of anosmia, memory deficits, and cerebellar ataxia. Elderly patients and/or patients with underlying neurological diseases were more susceptible and had worsened symptoms. Potential disease mechanisms underlying neurological symptoms observed in severe COVID-19 are vascular and fluid-brain barrier abnormalities, chronic neuroinflammation, persistent axonal damage and protein aggregation. In PASC patients, an altered biofluid proteome with increased neuronal proteins and pro-inflammatory cytokines was observed. The pathological burden in affected brain regions may contribute to manifestations such as anosmia, memory deficits, and cerebellar ataxia.},
}
@article {pmid42020802,
year = {2026},
author = {Steifman, CB and Alvarez-Carcamo, B and Verma, S and McCarthy, R and Guthrie, LB and Gill, KK and Swank, Z and Walt, DR and Grabowski, EF and Fasano, A and VanElzakker, MB and Irimia, D and Yonker, LM},
title = {Endovascular profiles linked to neutrophil activation in children and young adults with long COVID.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {42020802},
issn = {1530-0447},
abstract = {BACKGROUND: Endovascular symptoms are among the most debilitating long COVID symptoms; however, underlying mechanisms are unclear. Children and young adults with long COVID, an understudied population, offer key insight into long COVID pathology.<br><br>METHODS: Eighty-four children and young adults &#x2264;25 years from the U.S. and Canada were enrolled; 61 with long COVID and 23 healthy pediatric controls. We assessed symptom burden, quantified fibrin amyloid microclots, endovascular cytokines, cell-free DNA, and conducted in vitro assays to assess Spike-related neutrophil-mediated endothelial cell injury.<br><br>RESULTS: Cardiovascular symptoms were prevalent among participants with long COVID. Microclot burden was increased (p&#x2009;=&#x2009;0.0003), as were markers of angiogenesis and endothelial remodeling, including FGF-2, which correlated with microclots (p&#x2009;=&#x2009;0.04). Cytokines involved in leukocyte trafficking (sVCAM-1, L-selectin, &#x3b1;-2-macroglobulin) were reduced while cell-free DNA, a marker of intravascular neutrophil extracellular trap (NET) formation, was increased (p&#x2009;=&#x2009;0.003) and positively correlated with microclot component serum amyloid A (p&#x2009;=&#x2009;0.004). Co-culture assays revealed that NETosis, triggered by Spike immune complexes, contributes to endothelial injury in long COVID.<br><br>CONCLUSIONS: Children and young adults with long COVID with cardiovascular symptoms display increased microclots, endothelial injury, and neutrophil inflammation, which warrant further evaluation and suggest intravascular NETosis as a key driver of endovascular pathology in long COVID.<br><br>IMPACT: Children and young adults with long COVID display elevated endothelial biomarkers, underscoring disease-related rather than age-related endovascular profiles following SARS-CoV-2 infection. Children and young adults with long COVID exhibit increased microclot burden in blood. Neutrophil activation may contribute to ongoing endovascular injury in long COVID. A combination of microclots, neutrophil markers, and endothelial cytokines could serve as biomarkers for Long COVID.},
}
@article {pmid42008509,
year = {2026},
author = {Ortega-Martin, E and Alvarez-Galvez, J},
title = {Understanding quality-of-life patterns in long COVID: How Symptoms and socioeconomic conditions shape patient wellbeing.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0347743},
doi = {10.1371/journal.pone.0347743},
pmid = {42008509},
issn = {1932-6203},
mesh = {Humans ; *Quality of Life ; Male ; Female ; Middle Aged ; *COVID-19/epidemiology/psychology/pathology ; Cross-Sectional Studies ; Adult ; Aged ; Spain/epidemiology ; Socioeconomic Factors ; SARS-CoV-2/isolation &amp; purification ; Surveys and Questionnaires ; Fatigue ; Social Support ; },
abstract = {OBJECTIVE: To characterize the heterogeneity of Long COVID (LC) by identifying distinct patient profiles based on symptoms and quality of life (QoL), and to examine the sociodemographic and clinical predictors associated with these profiles.<br><br>STUDY DESIGN: A cross-sectional observational study was conducted.<br><br>METHODS: We recruited 363 patients with LC in Spain via an online survey. Symptom patterns were identified through latent class analysis of 15 binary symptoms. QoL was assessed with the patient-derived LC-6D-QoL across six dimensions, and cluster analysis defined QoL subgroups. Logistic regression was applied to examine clinical and sociodemographic predictors of QoL profiles.<br><br>RESULTS: Two symptom profiles emerged: a low-burden profile, dominated by fatigue and cognitive problems, and a high-burden profile with multisystem involvement. QoL clustered into three profiles-high, middle, and low QoL-with more than half of participants in the low QoL group. Symptom burden and employment status were the strongest predictors of poor QoL, whereas age, sex, education, and income showed limited associations. Social support was more frequently reported among participants with low QoL.<br><br>CONCLUSIONS: LC is characterized by distinct clinical and QoL profiles, with strong interactions between multisystem symptom burden and social determinants. Identifying patients at greatest risk of poor QoL can inform stratified interventions and integrated policies that combine medical care, psychosocial support, and workplace reintegration.},
}
@article {pmid42010131,
year = {2026},
author = {Floridia, M and Weimer, LE and Bonfanti, P and Forte, AL and Cogliandro, V and Bottaro, V and Andreozzi, P and Zucco, S and Vagheggini, G and Onder, G},
title = {Cognitive impairment in long-COVID: frequency, trajectories and risk factors in a cohort study from Italy.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {5},
pages = {},
pmid = {42010131},
issn = {1590-3478},
support = {I85F21003410005//Ministero della Salute/ ; },
}
@article {pmid42010493,
year = {2026},
author = {Köhrer, S and Brand, ML and Leidner, V and Zimmer, H and Langel, A and Langel, J and Michl, P and Mohr, I},
title = {Exploratory longitudinal cohort study of modest bilirubin-driven biochemical liver alterations after SARS-CoV-2 infection in a selected subgroup of patients with Wilson's disease and liver cirrhosis.},
journal = {BMC gastroenterology},
volume = {26},
number = {1},
pages = {},
pmid = {42010493},
issn = {1471-230X},
}
@article {pmid42011141,
year = {2026},
author = {Lloyd-Jones, G and Santamarina, M and Alcock, R and Oudkerk, M},
title = {Acute COVID-19 lung disease and long COVID vascular pathophysiology modelling: the relevance of medical imaging in building multidisciplinary understanding.},
journal = {The British journal of radiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/bjr/tqag056},
pmid = {42011141},
issn = {1748-880X},
abstract = {In this review, imaging features of COVID-19 lung disease are analysed in the context of pathophysiological processes in different phases of the disease. Radiological evidence is presented for the central role of vasculopathic phenomena in both the acute and post-acute phases of COVID-19. Radiologists have a central role in building understanding of many diseases. In multidisciplinary settings, medical imaging has a role in diagnosing, assessing severity, monitoring progress and delineating anatomy involved in diseases. Imaging also helps to elucidate models of disease pathogenesis. At the outset of the COVID-19 pandemic many groups worked together informally to gain understanding of pathogenesis, but no centralised system for formal interdisciplinary collaboration existed. In hindsight, the absence of formalised radiological involvement in building models of pathophysiology potentially contributed to the use of terminology which may be considered inappropriate or misleading. We reflect on the use of certain terminology commonly used to describe the lung disease. In conclusion, imaging is essential to multidisciplinary understanding of COVID-19 vascular pathophysiology both in the acute and post-acute phases of disease. Formation of collaborative systems to build interdisciplinary understanding of disease pathogenesis across all medical and scientific specialties should be a priority at the outset of any future pandemic.},
}
@article {pmid42011214,
year = {2026},
author = {Tan, C and Meng, J and Dai, X and He, B and Liu, P and Wu, Y and Xiong, Y and Yin, H and Wang, S and Gao, S},
title = {Corrigendum to 'Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials'.},
journal = {EClinicalMedicine},
volume = {94},
number = {},
pages = {103887},
pmid = {42011214},
issn = {2589-5370},
abstract = {[This corrects the article DOI: 10.1016/j.eclinm.2026.103883.][This corrects the article DOI: 10.1016/j.eclinm.2026.103882.][This corrects the article DOI: 10.1016/j.eclinm.2025.103412.].},
}
@article {pmid42013972,
year = {2026},
author = {Sagoo, R and Sagoo, NS and Nguyen, K and Sathyamoorthy, M},
title = {Sex-Based Differences in Cardiovascular Diagnoses, Mortality, and Resource Utilization in Long COVID Hospitalizations: A National Inpatient Sample Analysis.},
journal = {The American journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjcard.2026.04.027},
pmid = {42013972},
issn = {1879-1913},
abstract = {Long COVID refers to persistent sequelae following SARS-CoV-2 infection, and sex-specific cardiovascular outcomes among hospitalized patients remain incompletely characterized. We queried the 2022 National Inpatient Sample (NIS) to identify adult hospitalizations with a diagnosis of long COVID (ICD-10 U09.9), excluding patients younger than 18 years or with missing outcome data. Analyses incorporated NIS discharge weights to generate national estimates. Multivariable (survey-weighted) logistic regression was used to estimate adjusted odds ratios (aORs) for cardiovascular diagnoses and in-hospital mortality. Among 87,415 weighted hospitalizations for long COVID, 49.4% were male and 50.6% were female. Males had more complicated hypertension, coagulopathy, and alcohol use disorder, whereas females had higher rates of obesity, depression, and hypothyroidism (all p<0.05). Males had a higher in-hospital mortality rate (5.9% vs. 4.7%, p<0.001). In adjusted analyses, females had lower odds of in-hospital mortality (aOR: 0.874 [95% CI, 0.819-0.932]), cardiac arrhythmias (aOR: 0.652 [0.629-0.677]), venous thromboembolism (aOR: 0.846 [0.807-0.887]), and myocardial infarction (aOR: 0.767 [0.720-0.817]). Adjusted odds of ischemic cerebrovascular accident were not significantly different (aOR: 0.955 [0.795-1.146]). Females had higher odds of transient ischemic attack (aOR: 1.441 [1.067-1.945]). Median length of stay (5 vs. 4 days) and total hospital charges ($50,447 vs. $43,839) were lower in females (all p<0.001). In conclusion, in this nationally representative analysis of long COVID hospitalizations, sex-based differences were observed in cardiovascular diagnoses, mortality, and healthcare utilization, and these findings support sex-sensitive risk stratification and hypothesis generation for post-COVID care.},
}
@article {pmid42001973,
year = {2026},
author = {Mery, V and Albacar, N and Matute-Villacís, M and Dalmases, M and Sibila, O and Agustí, &#xc0; and Embid, C},
title = {"High prevalence of obstructive sleep apnea in patients with Long-COVID".},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108848},
doi = {10.1016/j.rmed.2026.108848},
pmid = {42001973},
issn = {1532-3064},
abstract = {BACKGROUND: Long-COVID (LC) is defined as the persistence of symptoms 12 weeks after the acute COVID infection not explained by any other alternative diagnosis. Its pathophysiology is poorly understood. Obstructive Sleep Apnea (OSA) shares several clinical manifestations with LC, such as fatigue and low-quality sleep, however, thus far, their potential coexistence has been poorly addressed.<br><br>OBJECTIVE: To investigate the prevalence of OSA in patients with LC.<br><br>METHODS: Observational, prospective study. Patients with LC were recruited from a dedicated ambulatory hospital clinic. All patients underwent a comprehensive clinical evaluation, including standardized questionnaires to evaluate persistent symptoms, lung function tests and full polysomnography.<br><br>RESULTS: We studied 73 patients with LC. Their mean age was 57.4 &#xb1; 10.5 years, they were predominantly male (56.2%), 73.9% of whom were hospitalized during the acute COVID episode. Median AHI was 17.2 (24.14) events/h with a proportion of mild (27.4%), moderate (24.6%) and severe OSA (31.5%). Objective questionnaires identified poor sleep quality and fatigue as the most prevalent symptoms and daytime sleepiness as the least prevalent. Self-reported symptoms were frequent, with dyspnea, fatigue, and insomnia being the most commonly reported. Neither objective nor subjective symptoms correlated with OSA severity, with the exception of insomnia.<br><br>CONCLUSION: In this single-center, clinic-based LC cohort, OSA diagnosed by in-lab PSG was highly common. Given that OSA is treatable, a sleep study should be considered in LC patients even in the absence of daytime sleepiness or in the presence of insomnia.},
}
@article {pmid42004170,
year = {2026},
author = {Li, Y and Shan, T and Jiang, Z and Han, F and Ma, J and Ni, H and Peng, J and Xu, M},
title = {Enduring coagulopathy and endothelial dysfunction in postacute COVID-19 syndrome.},
journal = {Blood vessels, thrombosis &amp; hemostasis},
volume = {3},
number = {2},
pages = {100147},
pmid = {42004170},
issn = {2950-3272},
abstract = {Postacute coronavirus disease 2019 (COVID-19) syndrome (PACS), or long COVID, encompasses a range of symptoms persisting beyond the acute phase of severe acute respiratory syndrome coronavirus 2 infection. Although acute-phase coagulation disturbances in COVID-19 are well documented, these abnormalities during recovery and their association with PACS remain inadequately explored. Our study aimed to investigate the long-term changes in coagulation function and inflammatory markers in patients with PACS, elucidating their pathological mechanisms and providing insights for patient management. This retrospective cohort study included 3783 adult inpatients in Jinan, China, divided into COVID-19-positive and -negative groups, with 363 patients with COVID-19 further diagnosed with PACS. Coagulation and inflammatory markers were collected at baseline and during 1-year follow-up, and changes over time were analyzed using generalized estimating equations. Most inflammatory markers and some coagulation parameters showed significant recovery, including lymphocyte counts and fibrinogen. However, several parameters remained abnormal even at 7 to 12 months after infection. Of note, D-dimer (Z = 5.692, P < .001, abnormal rate 65.79%) and erythrocyte sedimentation rate (Z = 2.749, P = .006, abnormal rate 57.32%) remained elevated above the normal upper limit. Additionally, certain coagulation parameters, particularly prothrombin time (β = -0.10 [95% confidence interval, -0.88 to 0.69]; P = .81, prolonged rate 17.29%) and platelet counts, did not normalize by 7 to 12 months. Our findings in survivors of severe COVID-19 pneumonia support the concept of PACS as a chronic thromboinflammatory syndrome characterized by sustained coagulation abnormalities. The prolonged elevation of D-dimer and incomplete recovery of coagulation parameters highlight the need for long-term monitoring and personalized management strategies to mitigate thrombotic risks in survivors of COVID-19.},
}
@article {pmid42004496,
year = {2026},
author = {Omdal, R and Lenning, OB and Jonsson, G and Kvaløy, JT and Skoie, IM and Braut, GS and Grimstad, T},
title = {Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {54},
number = {},
pages = {101226},
pmid = {42004496},
issn = {2666-3546},
abstract = {BACKGROUND: Fatigue persists as a dominant and debilitating phenomenon in long-COVID, yet its underlying biological mechanisms remain unclear. While inflammatory variables tend to normalize within months post-infection, fatigue continues to significantly impact quality of life. Understanding whether specific biomarkers associate with long-COVID fatigue could shed light on pathophysiological mechanisms and potential therapeutic targets.<br><br>METHODS: In this single-center, cross-sectional controlled study, we enrolled 48 individuals with long-COVID (according to NICE criteria) and 48 age- and sex-matched recovered controls with prior SARS-CoV-2 infection but no persistent symptoms. We carefully excluded all subjects with other diseases or conditions that could influence fatigue levels. Fatigue severity was assessed using three validated instruments: Fatigue Visual Analog Scale (fVAS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and SF-36 vitality subscale. Blood samples were analyzed for pro-inflammatory markers (CRP, TNF-&#x3b1;, IL-6, IL-1&#x3b2;) and biomarkers associated with cellular stress responses and neuroprotection (HSP90&#x3b1;, APOA4, Serpin F1/PEDF, Hemopexin). Anti-nuclear antibodies (ANA) were tested to assess potential autoimmune mechanisms. Depression was assessed using the Hospital Anxiety and Depression Scale, Depression Subscale (HADS-D).<br><br>RESULTS: Long-COVID patients demonstrated significantly higher fatigue severity across all instruments compared to recovered controls: fVAS median scores 63 versus 5 (p&#xa0;<&#xa0;0.001), FACIT-F scores 21.5 versus 49 (p&#xa0;<&#xa0;0.001), and SF-36 vitality scores 25 versus 72.5 (p&#xa0;<&#xa0;0.001). Depression scores were also significantly elevated in long-COVID cases. However, none of the measured biomarkers differed significantly between groups: HSP90&#x3b1;, Serpin F1, Hemopexin, APOA4, and CRP showed no differences, while TNF-&#x3b1; and IL-6 showed only tendencies toward higher levels in long-COVID (p&#xa0;=&#xa0;0.07 and p&#xa0;=&#xa0;0.07, respectively). IL-1&#x3b2; concentrations were in most cases below the lower limit of detection and were excluded from further analysis. ANA positivity was 10.4% in cases versus 4.2% in controls (p&#xa0;=&#xa0;0.38) and did not influence fatigue levels. Multivariable regression analysis revealed no significant associations between biomarkers and fatigue severity.<br><br>CONCLUSIONS: Fatigue in long-COVID represents severe, persistent disability comparable to observations in chronic inflammatory diseases and chronic fatigue syndrome but is not associated with traditional inflammatory biomarkers or cellular stress response proteins measured in peripheral blood. The absence of biomarker associations suggests that long-COVID fatigue may involve more complex mechanisms, potentially including persistent neuro-immune dysregulation, epigenetic changes, or pathophysiological processes not reflected in systemic biomarker concentrations including neurobiological mechanisms such as altered predictive processing and central nervous system-confined neuroinflammation. These findings highlight the need for alternative approaches to understanding and treating long-COVID fatigue beyond conventional inflammatory paradigms.},
}
@article {pmid42004523,
year = {2026},
author = {Petranu, K and Ford, T and Henley, D and Hammond, E and Henley, J and Crawford, M and Coleman, Z and Hirschtick, J},
title = {Exploring Long COVID diagnostic equity by sex, race and ethnicity, and insurance type.},
journal = {Preventive medicine reports},
volume = {65},
number = {},
pages = {103459},
pmid = {42004523},
issn = {2211-3355},
abstract = {OBJECTIVE: Our study explored Long COVID diagnostic inequity by comparing the demographic profile of patients diagnosed with Long COVID to patients diagnosed with COVID-19.<br><br>METHODS: Using electronic health record data from Advocate Health-Midwest between March 1, 2020, to November 1, 2023, we compared the proportion of all patients with documentation of Long COVID versus COVID-19 by race/ethnicity, sex, insurance type, and varying combinations of these characteristics.<br><br>RESULTS: Relative to COVID-19, a greater proportion of patients diagnosed with Long COVID were female (63.7% vs. 58.0%), non-Hispanic (NH) White (66.4% vs 62.9%), or covered by private insurance (53.8% vs 51.3%), and a lower proportion were Hispanic (12.1% vs. 14.3%) or covered by Medicaid (11.9% vs. 14.3%). Among patients with Medicaid, NH Black patients were underrepresented by 5.4 percentage points in the Long COVID sample vs. COVID-19 (25.2% vs. 30.6%), while NH White patients were overrepresented by 6.7 percentage points in the Long COVID sample compared to COVID-19 (48.2% vs. 41.5%).<br><br>CONCLUSIONS: Long COVID diagnostic estimates may be skewed towards patients that are more willing and able to seek care, while patients who experience multiple forms of disadvantage may be at risk for underdiagnosis due to compounding barriers to diagnosis.},
}
@article {pmid42007006,
year = {2026},
author = {Tamariz, L and Milanes, I and Bast, E and Shehadeh, LA and Klimas, N and Palacio, A},
title = {Elevated blood viscosity is associated with dysautonomia in long COVID symptoms.},
journal = {American heart journal plus : cardiology research and practice},
volume = {65},
number = {},
pages = {100776},
pmid = {42007006},
issn = {2666-6022},
abstract = {BACKGROUND: Long COVID is associated with elevated inflammatory and antibody levels. Elevated plasma proteins can increase blood viscosity and decrease blood flow. Our aim is to evaluate if blood viscosity is associated with long COVID outcomes.<br><br>METHODS: We conducted a cross-sectional study and included a sample of patients enrolled in our long COVID clinic. We estimated whole blood viscosity (WBV) using two previously validated formulas and compared it with the NASA lean test, COMPASS-31 scale as measures of dysautonomia and the symptom burden as measured by the modified COVID-19 Yorkshire scale. We obtained WBV at three different shear stress. We divided WBV and evaluated the distribution of symptom scores using univariate and multivariate models.<br><br>RESULTS: We included 185 patients for this study. Our sample had a mean age of 56&#xa0;&#xb1;&#xa0;11&#xa0;years, included 53% minorities and 32% were women. The mean C19-YRSm did not change with increasing tertile of WBV (p&#xa0;>&#xa0;0.05) while the mean COMPASS-31 score increased with increasing tertile of WBV in all levels of shear stress. In adjusted models the beta-coefficient of the C19-YRSm was (B -0.19p&#xa0;=&#xa0;0.90) and for COMPASS-31 was (B 7.0 p&#xa0;=&#xa0;0.01) for 208&#xa0;s[-1] and for all other levels of shear stress Twenty-three percent of patients in tertile 1 had either POTS or orthostatic hypotension compared to 32% on tertile 3 (p&#xa0;=&#xa0;0.04).<br><br>CONCLUSION: Whole blood viscosity was associated with dysautonomia and not with long COVID symptoms.},
}
@article {pmid41998026,
year = {2026},
author = {Chowdhury, MMH and Quenum, AJI and Rioux-Perreault, C and Lucier, JF and Ilangumaran, S and Piché, A and Allard-Chamard, H and Ramanathan, S},
title = {Distinct plasma proteome signature at 3 months post-COVID-19 infection irrespective of post-COVID condition.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-46180-y},
pmid = {41998026},
issn = {2045-2322},
support = {GA4-177773/CAPMC/CIHR/Canada ; 202309PPE-512214/CAPMC/CIHR/Canada ; },
abstract = {Persistent symptoms following SARS-CoV-2 infection are the hallmark of post-COVID condition (PCC), also referred to as long COVID. However, the underlying molecular mechanisms remain poorly understood. In this study, we employed data-independent acquisition mass spectrometry (DIA-MS)-based plasma proteomics to identify molecular alterations associated with PCC. DIA-MS proteomic analysis revealed a clear distinction between the plasma proteome of uninfected individuals and those previously infected with SARS-CoV-2, irrespective of PCC status. PCC samples demonstrated downregulation of the antioxidant protein peroxiredoxin 6 (PRDX6) and upregulation of oxidative stress-associated proteins, particularly vanin-1 (VNN1) and paraoxonase-3 (PON3). Additionally, individuals with PCC exhibited significantly elevated levels of six proteins-PCSK9, CST3, C1Q, CPB2, KNG1, and GAPDH-associated with glycolysis, complement and coagulation cascades, and inflammatory pathways. Validation by ELISA does not necessarily reflect the proteomics data suggesting the requirement for alternate methods of validation. Nonetheless, oxidative stress, as measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), further showed that PCC samples had significantly higher levels of DNA damage, compared with convalescent individuals. Antioxidant markers, including reduced and oxidized glutathione (GSH and GSSG), were significantly lower in PCC samples than in uninfected controls. Collectively, these findings indicate that plasma proteomic alterations persist for at least 3 months following SARS-CoV-2 infection, with additional disruptions in oxidative stress and inflammatory pathways characterizing individuals with PCC.},
}
@article {pmid41993482,
year = {2026},
author = {Lu, P and Izzy, S and Da Silva, P and Imkamp, HT and Christenson, JR and Yahya, T and Mansi, MHA and Alawi, A and Moreira, TG and Monje, M and Weiner, HL and Iwasaki, A},
title = {Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.07.716934},
pmid = {41993482},
issn = {2692-8205},
abstract = {Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-κB-driven inflammatory state toward chemokine signaling, phagosome, and TGF β-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.},
}
@article {pmid41993604,
year = {2026},
author = {Colgan, DD and Buttolph, L and Grow, T and Stadler, DD and Ruddick, M and Davenport, TE and Zwickey, H},
title = {Designing Nutrition Studies for Long COVID and Related Infection-Associated Chronic Illness: Qualitative Insights From a Patient-Reported Evaluation of Ketogenic Metabolic Therapy.},
journal = {Journal of patient experience},
volume = {13},
number = {},
pages = {23743735261442541},
pmid = {41993604},
issn = {2374-3735},
abstract = {BACKGROUND: Long COVID affects over 400 million people worldwide and has no FDA-approved treatments. Patients often rely on self-directed strategies, making their lived experiences an essential, yet underutilized, source of evidence. Ketogenic metabolic therapy (KMT) has demonstrated mechanisms relevant to Long COVID, including improved mitochondrial energy production, reduced oxidative stress, and modulation of inflammation, but remains underexplored.<br><br>METHODS: We conducted a cross-sectional, mixed-methods study of adults who completed Enable Your Healing, a 12-week virtual program integrating KMT with lifestyle components. Recruitment emails were sent to 194 participants; 41 completed the online REDCap survey. Quantitative data were summarized descriptively. Qualitative data were analyzed using conventional content analysis.<br><br>RESULTS: Participants (mean age 41; 90% female) reported diagnoses including postviral dysautonomia, myalgic encephalomyelitis/chronic fatigue syndrome, and Long COVID. Four themes emerged: program benefits, challenges, recommendations, and scientific considerations. Key insights included the value of multicomponent synergy, extended duration, and prioritization of functional outcomes.<br><br>CONCLUSION: Findings suggest nutrition trials for infection-associated chronic illnesses, including Long COVID, should consider incorporating longer intervention periods, multicomponent design, patient-centered outcomes, lived-experience integration, and tailored supports to optimize feasibility and impact.},
}
@article {pmid41993998,
year = {2026},
author = {Mogensen, DG and Dreyer, P and Backer, V and Jarden, M},
title = {Living with a hidden disability - a qualitative study of post-COVID-19 olfactory dysfunction.},
journal = {Frontiers in allergy},
volume = {7},
number = {},
pages = {1792460},
pmid = {41993998},
issn = {2673-6101},
abstract = {INTRODUCTION: Since the onset of the COVID-19 pandemic, olfactory dysfunction has become increasingly prevalent, manifesting as complete loss of smell, reduced olfactory sensitivity, or distorted perceptions such as parosmia. This qualitative study explored how post-COVID-19 olfactory dysfunction is experienced and how it impacts daily life, well-being, and quality of life.<br><br>METHODS: A qualitative design inspired by Ricoeur's phenomenological-hermeneutic approach was used. Twenty patients with post-COVID-19 olfactory dysfunction were recruited from an otolaryngology department in Denmark and interviewed between June 2023 and February 2024. Transcribed data were analyzed using Dreyer and Pedersen's Ricoeur-inspired method. The Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was applied.<br><br>RESULTS: The analysis revealed six themes: 1) Smell loss means relying on others' sense of smell, 2) A sudden fear of body odor, 3) The smell of decay and dreadful taste take over, 4) Losing the pleasure of food and finding comfort in overeating, 5) The loss of the ability to recall and experience meaningful scents, and 6) Living with a hidden disability.<br><br>CONCLUSIONS: Olfactory dysfunction after COVID-19 is experienced as an invisible yet intrusive condition that impacts daily functioning, eating habits, social relationships and personal identity. The findings highlight the need for greater awareness among healthcare professionals to support patients in developing coping strategies that promote quality of life in the context of long-term sensory loss.},
}
@article {pmid41994117,
year = {2026},
author = {Byrareddy, S and Kumar, N and Acharya, A and Das, R and Sardarni, U and Olasunkanmi, O and Murakonda, S and Sutar, D and Venkatesan, A and Ampasala, D and Cohen, S and Samuelson, M and Sajja, B and Dettmer, U and Ramalingam, N and Chand, H},
title = {Sex- and Age-Dependent Neuroimmune Dysregulation and Early Neurodegenerative Signatures Following SARS-CoV-2 Infection in Golden Syrian Hamsters.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9130692/v1},
pmid = {41994117},
issn = {2693-5015},
abstract = {Post-acute sequelae of SARS-CoV-2 infection, or Long-COVID, affects millions globally and is characterized by persistent symptoms affecting multiple organs, yet the underlying mechanisms remain poorly defined. Here, we used Golden Syrian Hamsters (GSH) infected with the SARS-CoV-2 to investigate how sex and age shape viral persistence, organ-specific pathology, immune responses, and neurological outcomes during acute infection and Long-COVID. We show that during Long-COVID, viral RNA persists only in the lungs of male hamsters. Lung pathology revealed sustained inflammation and tissue remodeling, with young females exhibiting greater fibrosis. Transcriptomic profiling across brain, lung, and heart identified pronounced sex- and age-dependent regulation of gene expression spanning immune, neuroinflammatory, and neurotransmitter signaling pathways. These transcriptomic alterations were accompanied by sex-specific behavioral changes and persistent microstructural remodeling in cognition-associated brain regions. Additionally, SARS-CoV-2 altered α-synuclein homeostasis and microglial activation alongside gut microbiome composition in a sex- and age-dependent manner. Together, our findings demonstrate that, in GSH Long-COVID is strongly modulated by sex and age, influencing viral RNA persistence, immune and neurobiological responses, and gut microbiota composition mirroring clinical outcomes reported in human cohorts. This study establishes SARS-CoV-2-infected GSH as a model for dissecting the mechanisms of Long-COVID and informing targeted prevention strategies.},
}
@article {pmid41995128,
year = {2026},
author = {Gonah, L and Ginindza, TG and Hlongwana, KW},
title = {Mapping global evidence on compassion fatigue among healthcare workers during COVID-19: insights and implications for future preparedness - a scoping review.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04130},
doi = {10.7189/jogh.16.04130},
pmid = {41995128},
issn = {2047-2986},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Health Personnel/psychology ; *Compassion Fatigue/epidemiology ; Risk Factors ; SARS-CoV-2 ; Prevalence ; Global Health ; Burnout, Professional/epidemiology ; Female ; },
abstract = {BACKGROUND: Compassion fatigue (CF) is a critical occupational hazard for healthcare workers (HCWs), intensified by the COVID-19 pandemic, with implications for well-being, retention, and quality of care. We aimed to map the global evidence on CF prevalence, risk factors, effects, interventions, and research gaps among HCWs during the COVID-19 pandemic.<br><br>METHODS: A scoping review of 56 studies from 21 countries (2020-2025) was conducted following PRISMA-ScR guidelines. Seven databases were searched, and findings were synthesised narratively with attention to occupational, demographic, and systemic determinants of CF.<br><br>RESULTS: Compassion fatigue prevalence ranged from 20 to 87%. It was most pronounced among nurses, women, frontline staff, early-career professionals, and those in under-resourced or rural settings. Key risk factors included high workload, long shifts, repeated exposure to death, moral distress, and limited organisational support. Symptoms encompassed emotional exhaustion, depersonalisation, diminished empathy, and co-occurring anxiety, depression, or secondary traumatic stress. Interventions (resilience and peer-support programmes, self-compassion training, motivational messaging, and mobile psychoeducation) showed small-to-moderate benefits but were limited by methodological heterogeneity and scarce robust evaluation. Temporally, CF peaked during early pandemic surges and persisted among frontline staff and in resource-constrained or long-COVID contexts.<br><br>CONCLUSIONS: Compassion fatigue is a multifactorial, context-dependent hazard disproportionately affecting vulnerable HCWs. Effective mitigation requires longitudinal research, inclusive global representation, and multi-level strategies linking individual resilience with organisational reform and policy action to safeguard HCW well-being in current and future crises.},
}
@article {pmid41997565,
year = {2026},
author = {Rozewicz-Juraszek, M and Mueller, S and Ganbat, M and Bolanos, CR and Klement, A and Ugalde, SA and Halle, M and Nagel, E and Puntmann, V},
title = {Native T1 is independently associated with aerobic exercise capacity in long-term follow-up after mild initial COVID-19 disease (Impression COVID&amp;Heart Study).},
journal = {Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance},
volume = {},
number = {},
pages = {102725},
doi = {10.1016/j.jocmr.2026.102725},
pmid = {41997565},
issn = {1532-429X},
abstract = {BACKGROUND: Exercise intolerance is a common and incapacitating long-term consequence of COVID-19, even after mild acute illness. Cardiovascular magnetic resonance (CMR) studies have demonstrated persistent perimyocardial inflammatory abnormalities; however, their relationship with long-term aerobic capacity remains unclear.<br><br>METHODS: In this prospective observational study, individuals without prior structural heart disease underwent standardised CMR, echocardiography, and cardiopulmonary exercise testing (CPET) at least 3 years after the initial COVID-19. The primary endpoint was the association between %-predicted VO&#x2082;peak (age-sex-body mass index (BMI) adjusted, Study of Health in Pomerania (SHIP) reference) and imaging parameters. Secondary analyses included lactate measurements and sex-stratified models.<br><br>RESULTS: A total of 132 participants (mean age 49 &#xb1; 12 years; 68/132 (52%) male) were evaluated 48 months [interquartile range (IQR) 42-53] post-infection. Non-ischaemic perimyocardial enhancement was present in 34/132 (26%), whereas two participants had an unrecognised ischaemic scar. Male sex, higher BMI, lower age, and higher native T1 were associated with lower %-predicted VO&#x2082;peak in univariate models. In multivariate analysis, male sex, lower age, and higher native T1 (&#x3b2; = -0.25 per ms, 95% CI -0.40 to -0.10; p < 0.001) remained independent predictors of lower %-predicted VO&#x2082;peak. In total, 63/132 (48%) participants demonstrated %-predicted VO&#x2082;peak below predicted values. Sex-stratified multivariate analyses showed that higher native T1 (p<0.001) independently associated with lower %-predicted VO&#x2082;peak in both men and women, with lower age additionally retained in men. In a lactate-measured subgroup (n=73), higher resting lactate, higher native T1, male sex, and lower left atrial area were associated with lower %-predicted VO&#x2082;peak.<br><br>CONCLUSIONS: In long-term follow-up of individuals with mild initial COVID-19 and no prior structural heart disease, aerobic capacity relative to predicted values was reduced in 48% of participants, particularly in men, and was independently associated with higher myocardial native T1. Native T1 and resting lactate, but not conventional structural measures or peak exercise.},
}
@article {pmid41987304,
year = {2026},
author = {Alhumaid, S and Sabr, Z and Alshehri, SM and Alhashem, HA and Alnajjad, Q and Alsaadoun, DS and Algrafi, AS and Aborshaid, FA and Alsaidalani, AA and Noorsaeed, S and Al Nasser, DA and Majzoub, RA and Alkhars, O and Al Dossary, N and Banjar, SS and ALMuhaini, IA and Ismail, FA and Al Alawi, Z and Alalwan, QM},
title = {Asthma control and exacerbation risk following SARS-CoV-2 infection in the post-acute COVID-19 phase: a systematic review.},
journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13223-026-01027-z},
pmid = {41987304},
issn = {1710-1484},
}
@article {pmid41987944,
year = {2026},
author = {Mesquita da Fonseca, L},
title = {Commentary: A cross-continental comparative analysis of the neurological manifestations of Long COVID.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1798243},
pmid = {41987944},
issn = {1662-5161},
}
@article {pmid41990057,
year = {2026},
author = {Zhang, J and Zhao, W and Zhang, T and Wu, Q and Di, J and Mao, X},
title = {Impact of COVID-19 on the treatment outcomes of secretory otitis media.},
journal = {Journal of infection in developing countries},
volume = {20},
number = {3},
pages = {327-331},
doi = {10.3855/jidc.21341},
pmid = {41990057},
issn = {1972-2680},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; Adult ; *Otitis Media with Effusion/therapy/complications/drug therapy ; SARS-CoV-2 ; Aged ; Audiometry, Pure-Tone ; },
abstract = {INTRODUCTION: The World Health Organization (WHO) officially lifted the global emergency designation for coronavirus disease 2019 (COVID-19) in May 2023. Nonetheless, the long-term repercussions of the pandemic-referred to as 'long COVID'-have persisted. It is also highly likely for the disease to be complicated by secretory otitis media (SOM). This study aimed to determine if there is anything particularly distinctive about SOM associated with long-COVID, and could it affect the therapeutic outcomes of the latter.<br><br>METHODOLOGY: A total of 102 patients diagnosed with COVID-19-associated SOM between December 2022 and May 2023 were retrospectively analyzed. Pre- and post-treatment pure-tone audiometry thresholds were assessed to evaluate therapeutic efficacy. Follow-up assessments were performed at 1, 3, 6, and 12 months' post treatment, and the findings were compared with those of a control group of 98 patients who had SOM but not COVID-19 infection during the same time frame.<br><br>RESULTS: All patients showed normal hearing thresholds post treatment. A comparative analysis using a two-sample t-test revealed no statistically significant difference in the average speech-hearing thresholds between the two groups post-treatment (t = 0.099, p = 0.92). No recurrence was observed in either group during the year-long follow-up period.<br><br>CONCLUSIONS: Although COVID-19 is commonly associated with SOM, patients can expect satisfactory recovery of their hearing function with proactive treatment strategies.},
}
@article {pmid41991929,
year = {2026},
author = {Saak, TM and Tervo, JP and Jacobson, PT and Vilarello, BJ and Caruana, FF and Gallagher, LW and Gary, JB and Gudis, DA and Motter, JN and Goldberg, TE and Devanand, DP and Overdevest, JB},
title = {Longitudinal evaluation of neurocognitive outcomes in a cohort with persistent post-COVID olfactory dysfunction.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41991929},
issn = {2045-2322},
abstract = {Persistent COVID-19-associated olfactory dysfunction (C19OD), along with other neurologic and cognitive deficits are common features of long COVID. This study aims to evaluate longitudinal trends in neurocognitive performance within a cohort with C19OD. In individuals with perceived C19OD we performed serial psychophysical olfactory and neurocognitive assessments at baseline and follow-up one year later. At baseline evaluation, individuals with C19OD were found to have diminished cognitive functioning compared to normosmic counterparts across several domains, including attention, executive functioning, language, learning and memory, and psychomotor speed. At subsequent one-year follow-up assessment, C19OD participants demonstrated cognitive recovery, with performance comparable to normosmic counterparts. These findings suggest that early associations between C19OD and certain neurocognitive domains may dissipate upon repeated longitudinal evaluation, with partial resolution of cognitive deficits despite persistent C19OD.},
}
@article {pmid41982416,
year = {2026},
author = {Doenyas-Barak, K and Elman Shina, K and Lang, E and Finci, S and Elkarif, V and Shorer, R and Efrati, S},
title = {The effect of hyperbaric oxygen therapy on sleep quality across diverse patient populations.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1690633},
pmid = {41982416},
issn = {1664-2295},
abstract = {BACKGROUND: Sleep disturbances are common in aging, post-traumatic stress disorder (PTSD), and long COVID, often linked to neuroinflammation, autonomic dysregulation, and neurodegeneration. Hyperbaric oxygen therapy (HBOT) promotes neuroplasticity through the hyperoxic-hypoxic paradox, improving cerebral perfusion, mitochondrial function, and reducing inflammation. While HBOT benefits sleep in certain conditions, its general effects across clinical populations remain unclear.<br><br>METHODS: This retrospective longitudinal study evaluated Pittsburgh Sleep Quality Index (PSQI) changes in patients undergoing 60 HBOT sessions (2.0 ATA, 100% oxygen, 90&#x202f;min, 5&#x202f;days/week) at the Sagol Center. Participants included individuals treated for healthy aging (n&#x202f;=&#x202f;180), long COVID (n&#x202f;=&#x202f;92), or PTSD (n&#x202f;=&#x202f;123). Pre- and post-treatment PSQI total and component scores were compared using paired t-tests and Wilcoxon signed-rank test was used for PSQI components. Regression analysis identified predictors of improvement.<br><br>RESULTS: Among 395 patients (mean age at baseline 57.9&#x202f;&#xb1;&#x202f;14.6&#x202f;years, 31% female), baseline PSQI scores were highest in PTSD. Post-HBOT, total PSQI scores improved significantly in all groups (p&#x202f;<&#x202f;0.001; Cohen's d&#x202f;=&#x202f;0.37-0.91). Significant gains were observed in subjective sleep quality, sleep latency, and disturbances in all groups; daytime dysfunction improved in aging and long COVID but not PTSD. Medication use was unchanged. Baseline PSQI was a strong predictor of improvement (B&#x202f;=&#x202f;0.494, p&#x202f;<&#x202f;0.001, r&#x202f;=&#x202f;0.46). Those with disturbed sleep (PSQI>5) showed broad, statistically significant gains, while normal sleepers exhibited minimal changes.<br><br>CONCLUSION: HBOT was associated with improvement in sleep quality across diverse conditions, with greatest benefit in patients with poorer baseline sleep. Findings support HBOT's potential as a sleep-modulating therapy, warranting controlled trials to characterize the patients that can benefit the most and elucidate mechanisms.},
}
@article {pmid41984770,
year = {2026},
author = {Abbas, U and Laghari, RN and Ahmed, I and Musawwir, UA and Riaz, H and Anwar, K and Hussain, N and Mubeen, M and Khan, M and Khalid, MU and Ashraf, S},
title = {Acute SARS-CoV-2 viral load and systemic inflammation are associated with neuropsychiatric and musculoskeletal symptoms in long COVID.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346978},
doi = {10.1371/journal.pone.0346978},
pmid = {41984770},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/complications/virology/blood/psychology ; *Viral Load ; Male ; Female ; Middle Aged ; Retrospective Studies ; *SARS-CoV-2/isolation &amp; purification ; *Inflammation/blood/virology ; Adult ; Biomarkers/blood ; Aged ; *Musculoskeletal Diseases ; Interleukin-6/blood ; *Mental Disorders ; C-Reactive Protein/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long after recovery from acute-COVID illness, many patients show persistent multi-organ dysfunction consistent with Long COVID. Biochemical profile and measurements of inflammatory markers in these individuals can help to understand the underlying pathophysiology. This study aims to evaluate biochemical markers and their association with symptoms of Long COVID. We, in a retrospective analysis, also examined whether the Long COVID symptom persistence is associated with the SARS-CoV-2 viral load documented during the acute infection.<br><br>METHODS: A total of 300 participants with previously diagnosed mild COVID-19 were recruited at 10 months post-infection. Brief clinical history was taken based on persistent symptoms after COVID-19 and categorized as Long COVID (n&#x2009;=&#x2009;177) and controls group (n&#x2009;=&#x2009;123) based on WHO defined criteria. Biochemical parameters in blood like complete blood count (RBC and WBC indices) were compared between the groups. Other measurements including inflammatory markers such as IL-6, IL-10, ferritin and C-reactive protein along with electrolytes, vitamin D3 and B12, and lipid profile, were also compared. SARS-CoV-2 viral load was assessed retrospectively. Data was analyzed through SPSS v.26.<br><br>RESULTS: The findings of our study revealed that 59% (177) of individuals had symptoms of Long COVID. The most frequently reported symptoms of Long COVID were related to neuropsychiatry (35%), followed by musculoskeletal system (32.2%). The Hemoglobin, RBC counts and MCHC were decreased in Long COVID as compared to control group (p&#x2009;<&#x2009;0.05). While Lymphocytes, IL-6 and ferritin levels were raised in Long COVID group (p&#x2009;<&#x2009;0.05). In multivariable logistic regression analyses adjusted for age and sex, neuropsychiatric symptoms were independently associated with higher lymphocyte counts (aOR 1.19, 95% CI 1.12-1.51), IL-6 (aOR 1.16, 95% CI 1.10-1.86), ferritin (aOR 1.42, 95% CI 1.10-1.53), and vitamin D deficiency (aOR 1.45, 95% CI 1.22-2.01). Musculoskeletal symptoms were strongly associated with vitamin D deficiency (aOR 2.30, 95% CI 1.20-4.50) and ferritin levels (aOR 0.98, 95% CI 0.97-0.99). Moreover, higher SARS-CoV-2 viral load (CT&#x2009;&#x2264;&#x2009;20) during acute infection was also associated with neuropsychiatric and musculoskeletal symptoms of Long COVID.<br><br>CONCLUSION: We identified Long COVID in 59% of the participants, the highest reported percentage in studies in the middle-aged individuals. Compared to controls, we found differential biochemical markers in the Long COVID group indicating a different metabolic status in these individuals. Moreover, the association of raised inflammatory markers at ten months follow up and acute-phase SARS-CoV-2 viral load were also seen to be associated with musculoskeletal and neuropsychiatric symptoms of the Long COVID. These significant clinical and biochemical changes warrant thorough monitoring and follow-ups for extended time.},
}
@article {pmid41984971,
year = {2026},
author = {Jason, LA and Furst, J and Katz, BZ},
title = {Comparing ME/CFS following mononucleosis with Long COVID.},
journal = {Chronic illness},
volume = {},
number = {},
pages = {17423953251347108},
doi = {10.1177/17423953251347108},
pmid = {41984971},
issn = {1745-9206},
abstract = {ObjectivesLong COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are examples of post-infectious chronic illnesses. Behavioral and pathophysiological underpinnings of both ME/CFS following IM and Long COVID are not well understood.MethodsWe studied ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. We categorized those meeting either moderate or severe ME/CFS criteria. We subsequently recruited a matched sample of those infected with SARS-CoV-2, some of whom recovered and others of whom developed Long COVID. We compared and contrasted ME/CFS and Long COVID following IM and SARS-CoV-2 infection in terms of somatic symptoms, coping strategies, depression and anxiety symptoms, and functional status.ResultsIn general, the Long COVID group's symptom burden was less than that of the Severe ME/CFS group but more than that of the Moderate ME/CFS group.DiscussionThese findings may allow investigators a better understanding of these post-viral illness pathophysiologies.},
}
@article {pmid41985377,
year = {2026},
author = {Sekendiz, Z and Caliendo, M and Taboada, D and An, T and Palekar, N and Weisenbach, S and Kim, MJ},
title = {The neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation: Preliminary observations in a small cohort.},
journal = {Journal of the neurological sciences},
volume = {486},
number = {},
pages = {125915},
doi = {10.1016/j.jns.2026.125915},
pmid = {41985377},
issn = {1878-5883},
abstract = {BACKGROUND: The underlying mechanism of neuropsychiatric features of Long COVID remains unclear; however, the most compelling hypothesis is the contribution of excessive neuroinflammation induced by a systemic inflammatory response or cytokine storm. We aimed to investigate the neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation measured by [[18]F]FEPPA positron emission tomography (PET) targeting translocator protein (TSPO).<br><br>METHODS: A total of 24 individuals aged 60 or older participated in the study: those with Long COVID symptoms and persistent subjective or objective cognitive impairments for more than six months (n&#xa0;=&#xa0;12) and age-matched healthy adults without Long COVID (n&#xa0;=&#xa0;12). After assessments with neuropsychiatric scales and cognitive testing batteries, three Long COVID and three healthy control participants, who were high-affinity binders to TSPO, underwent additional brain [[18]F]FEPPA PET scans.<br><br>RESULTS: Long COVID group (n&#xa0;=&#xa0;12) showed significantly higher levels of depression and fatigue compared to the healthy control group (n&#xa0;=&#xa0;12). With [[18]F]FEPPA PET, the Long COVID group (n&#xa0;=&#xa0;3) showed significantly higher binding levels in all compared brain regions, such as the prefrontal, temporal, parietal, and occipital neocortices, and the hippocampus, thalamus, and cerebellum, compared to the healthy control group (n&#xa0;=&#xa0;3).<br><br>CONCLUSION: Older adults with Long COVID showed greater neuropsychiatric symptoms, such as depression and fatigue, compared to healthy older adults. The [[18]F]FEPPA PET findings suggest that their persistent neuropsychiatric symptoms could potentially be associated with chronic neuroinflammation.},
}
@article {pmid41975732,
year = {2026},
author = {Fanò-Illic, G and Coscia, F and Gigliotti, PV and Checcaglini, F and Carraro, U and Fulle, S and Mancinelli, R},
title = {Pathophysiological, Translational, and Diagnostic Aspects of ME/CFS: A Focus on Skeletal Muscle Involvement.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {7},
pages = {},
pmid = {41975732},
issn = {2075-4418},
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multisystemic disorder characterized by severe, persistent fatigue not alleviated by rest and worsened by minimal exertion, often accompanied by post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and autonomic disturbances. Despite decades of research, its pathophysiology remains incompletely understood, and skeletal muscle involvement has only recently gained attention. This review aims to provide a historical and pathophysiological synthesis of ME/CFS, emphasizing the pivotal role of skeletal muscle in the onset and persistence of symptoms, and to integrate molecular, cellular, and pathophysiological evidence into a coherent explanatory framework. This is a narrative review of published literature (1990-2025) with critical integration of clinical, biochemical, and experimental data on oxidative stress, mitochondrial dysfunction, Excitation-Contraction (E-C coupling) dysregulation, and muscle secretome alterations in ME/CFS also in relation to post-viral syndromes (e.g., Long COVID). Evidence consistently points to mitochondrial oxidative stress, redox imbalance, impaired Ca[2+] handling, and altered signaling pathways in skeletal muscle of patients with ME/CFS. Historical milestones show an evolution from psychogenic interpretations toward recognition of ME/CFS as a biological disorder with neuromuscular and metabolic underpinnings. ME/CFS can be interpreted as a skeletal muscle-metabolic disorder characterized by oxidative distress, mitochondrial dysfunction, and impaired energy regulation, leading to the clinical picture of exercise intolerance and post-exertional malaise. Integrating basic and clinical research through a translational approach provides the foundation for new diagnostic tools, targeted therapies, and biomarkers.},
}
@article {pmid41976810,
year = {2026},
author = {Barr, J and Marsden, L and Dassanayake, T and Almutairi, N and McKeever, V and Gaber, T and Tarrant, R and Godfrey, B and Witton, S and Sivan, M},
title = {Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID.},
journal = {Journal of clinical medicine},
volume = {15},
number = {7},
pages = {},
pmid = {41976810},
issn = {2077-0383},
support = {133038//The ME Association/ ; },
abstract = {Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are complex multisystem conditions with significant functional disability. Many patients experience symptoms of orthostatic intolerance, which can be captured in some cases as Orthostatic Hypotension (OH) or Postural orthostatic Tachycardia Syndrome (PoTS) on objective testing. Conservative treatments are recommended for first-line symptom management, but there is a lack of efficacy evidence. This study aims to assess the feasibility of an 8-week clinically supervised, personalised Dysautonomia Management Protocol (DMP) in a cohort of ME/CFS and LC patients with subjective and objective evidence of orthostatic intolerance (dysautonomia). Methods: ME/CFS and LC patients with objective dysautonomia on the 10 min active Lean Test (LT) were recruited to an 8-week DMP, with interventions introduced cumulatively every two weeks. Interventions included increasing daily fluid intake to 3 litres and salt intake to 10 g, pacing to avoid crashes and calf activation. Baseline and weekly data collection included the LT, Composite Autonomic Symptom Score questionnaire (COMPASS-31) and Yorkshire Rehabilitation Scale (YRS). Results: Sixteen participants completed the 8-week program, five discontinued during the program, and one was withdrawn following a severe crash. The COMPASS-31 improved by 7.7 points from week 1 to week 8 (p = 0.045), with a medium Cohen's d effect size of 0.55. For the same period, there was a non-significant (p = 0.16) improvement in the YRS symptom severity score by 2 points. Comparing the final two weeks of the program with the first two weeks, mean heart rate during the LT decreased by 4.8 beats per minute (p = 0.032), with a medium Cohen's d effect size of 0.44. Adherence to the interventions was highly variable, with none of the patients able to fully employ all four recommendations. Conclusions: The results suggest that targeted conservative interventions could influence autonomic function and symptom reduction. However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms.},
}
@article {pmid41976966,
year = {2026},
author = {Mihai, AM and Marc, M and Lucaciu, F and Sima, A},
title = {Incident Heart Failure Risk Following COVID-19 Recovery: A Systematic Review and Meta-Analysis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {7},
pages = {},
pmid = {41976966},
issn = {2077-0383},
support = {We would like to acknowledge the Victor Babes University of Medicine and Pharmacy, Timisoara, for paying the APC. The funder had no role in study design, data collection/analysis, decision to publish, or manuscript preparation//Victor Babe&#x219; University of Medicine and Pharmacy Timi&#x219;oara/ ; },
abstract = {Background/Objectives: While acute cardiac injury during COVID-19 is well-documented, the long-term risk of new-onset heart failure (HF) in survivors remains a critical clinical concern. This study aims to quantify the risk of new-onset heart failure during a 25 months prognostic follow-up period following recovery from SARS-CoV-2. Methods: We conducted a systematic review and meta-analysis of nine high-quality studies (n > 400,000 survivors) in accordance with PRISMA 2020 guidelines. Databases including PubMed/MEDLINE and Scopus were searched through January 2026. A quantitative meta-analysis was performed on six studies using a random-effects model to pool adjusted hazard ratios (aHR). Results: The pooled analysis revealed a significant 35% increased risk of new-onset heart failure following COVID-19 recovery (aHR 1.35; 95% CI: 1.14-1.60; p = 0.001). Significant heterogeneity was observed (I[2] = 92.62%), reflecting diverse risk profiles among survivors. The risk was most pronounced in immunocompromised kidney transplant recipients (aHR 2.32) and younger adults under the age of 65 (aHR 1.53). Subclinical myocardial damage, characterized by reduced left ventricular longitudinal strain, was identified even in survivors who experienced mild initial infections. Conclusions: COVID-19 recovery serves as a significant independent risk factor for chronic heart failure, emphasizing that cardiovascular impact extends far beyond the acute phase. These findings necessitate the implementation of structured cardiovascular monitoring and biomarker screening for at least one year post-infection to address this emerging chronic disease burden.},
}
@article {pmid41977143,
year = {2026},
author = {Jaishankar, S and Schaeper, D and Janga, SC and Srinivasan, M},
title = {Single-Cell Transcriptomic Analysis of Salivary Epithelial Cells Reveals Large-Scale Dysregulation in Bitter Taste Dysfunction.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
doi = {10.3390/ijms27072953},
pmid = {41977143},
issn = {1422-0067},
support = {4476254//Delta Dental Research and Development Committee/ ; },
mesh = {Humans ; *Epithelial Cells/metabolism ; Single-Cell Analysis/methods ; *Saliva/cytology/metabolism ; Gene Expression Profiling ; *Transcriptome ; Female ; *COVID-19/complications/genetics ; Male ; *Taste/genetics ; Middle Aged ; *Dysgeusia/genetics/metabolism ; Adult ; Toll-Like Receptor 2/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; Toll-Like Receptor 4/genetics/metabolism ; },
abstract = {Taste dysfunction, or dysgeusia, is a frequent symptom associated with infections and systemic diseases, yet its cellular and molecular basis remains poorly understood. The COVID-19 pandemic provided an opportunity to study dysgeusia as a "natural experiment" due to its high prevalence in those with acute and long COVID (LC). We investigated salivary epithelial cells (SECs) using single-cell RNA sequencing to elucidate molecular changes underlying taste dysfunction in LC. Functional enrichment analysis of SEC transcriptomes from individuals with bitter taste dysfunction (LC-D) revealed downregulation of genes involved in cytoskeletal dynamics and taste cell-nerve synapse assembly. Further, specific Type II and III taste receptor genes, critical for bitter taste perception, were reduced. Microbial defense markers such as Toll-like receptors TLR2 and TLR4 were also downregulated, suggesting chronic inflammation. These findings support a model of sustained dysregulated epithelial turnover due to impaired taste in LC-D. Saliva-based single-cell approaches offer promising tools for future diagnostics and mechanistic studies of taste systems.},
}
@article {pmid41978821,
year = {2026},
author = {Miller, DW and Rodgers-Melnick, SN and Deraz, NT and Dusek, JA and Segall, TL and Edwards, AM},
title = {Interdisciplinary Pediatric Long-COVID Care: A Descriptive Study of Interventions and Health-Related Quality of Life.},
journal = {Open forum infectious diseases},
volume = {13},
number = {4},
pages = {ofag155},
pmid = {41978821},
issn = {2328-8957},
abstract = {OBJECTIVES: Data on pediatric long-COVID is limited to descriptive reports of symptom prevalence and incidence, with few studies describing integrative care or including patient-reported quality of life. This study describes demographic, clinical, symptom severity, and intervention characteristics within a pediatric long-COVID clinic involving collaboration between infectious disease and integrative medicine physicians.<br><br>METHODS: Clinical data were extracted from the electronic health records for patients aged 4-25 with long-COVID seen within this clinic. A subset of patients completed validated PROs of wellbeing, fatigue, sleep-related impairment and disturbance, depression, and anxiety.<br><br>RESULTS: A cohort of 214 patients (mean age 14.7, 61% female, 83% White) were seen between March 2021 and June 2023, with 39.7% providing Pediatric Quality of Life Inventory (PedsQL) and 30.3% providing Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Common documented conditions included fatigue (85%), headache (75.2%), dizziness (64.5%), anxiety (62.1%), and nausea (59.3%). Common interventions included diet changes (81.8%), pacing (65.9%), sleep hygiene (61.2%), and other self-care techniques (46.7%). The long-COVID cohort reported elevated PROMIS sleep disturbance (61.79), sleep-related impairment (63.9), anxiety (58.1), and depression (58.1) as well as PedsQL total fatigue (40.19). These scores were more severe than national norms as well as compared with other pediatric chronic disease cohorts (eg, chronic pain, cancer, sickle cell disease, autism).<br><br>CONCLUSIONS: Pediatric patients with long-COVID report high symptom burden. This study describes patient characteristics, care delivered and provides a novel description of symptom severity. Future research among more diverse populations is needed to evaluate outcomes of this integrative care.},
}
@article {pmid41979136,
year = {2026},
author = {Kleeman, M and Nau, C and Su, J and Young, DR and Butler, R and Yang, LS and Batteate, C and Eng, S and Burnett, RT and Jerrett, M},
title = {Ambient Air Pollution and COVID-19 in California.},
journal = {Research report (Health Effects Institute)},
volume = {},
number = {238},
pages = {1-97},
pmid = {41979136},
issn = {1041-5505},
mesh = {Humans ; *COVID-19/epidemiology/mortality ; *Air Pollution/adverse effects/analysis/statistics &amp; numerical data ; California/epidemiology ; Particulate Matter/analysis/adverse effects ; *Environmental Exposure/adverse effects ; Middle Aged ; *Air Pollutants/analysis/adverse effects ; SARS-CoV-2 ; Male ; Female ; Aged ; Adult ; Risk Factors ; Incidence ; },
abstract = {INTRODUCTION: As of December 2023, more than 6.9 million people globally had died from COVID-19, including more than 1.165 million deaths in the United States. It is estimated that approximately 18.8 million people in the United States have experienced post-acute COVID-19 conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, in the first 3 years after the pandemic. Although some initial cases of long COVID have resolved, with the ongoing incidence of COVID-19, roughly 17.8 million persons in the United States continue to suffer from long COVID at the time of this writing.[1-3] Preliminary evidence early in the COVID-19 pandemic suggested that exposure to air pollution increased the likelihood of contracting COVID-19 and worsened outcomes for those who became ill. The validity of these findings was uncertain, however, as few studies used highly accurate exposure models incorporating individual-level data on patient characteristics and risk factors. Although the COVID-19 public health emergency has ended, the disease continues to pose substantial risks to individual and population health. At the time of this writing, nearly 35,000 individuals per week are hospitalized with COVID-19 in the United States, and the weekly number of COVID-19-related deaths ranges from 900 to 1,400.[4].<br><br>METHODS: In this study, we investigated relationships between ambient air pollution and COVID-19-related outcomes, including incidence, severity, mortality, and long COVID conditions. We used advanced models to estimate exposures, incorporating numerous air pollutants, particle species, and wildfire emissions. We used administrative COVID-19 data and several cohorts of patients from a large health system, and each was formed to evaluate different hypotheses.<br><br>UNLABELLED: Daily air pollution exposures for Southern California were estimated with high spatial and chemical resolution, using a combination of land use regression and chemical transport models for the years 2016, 2019, and 2020. Exposure variables included ozone (O3), nitrogen dioxide (NO2), fine particulate matter (PM) &#x2264;2.5 &#x3bc;m in aerodynamic diameter (PM2.5mass), ultrafine PM &#x2264;0.1 &#x3bc;m in aerodynamic diameter (PM0.1), and major sources or chemical components of PM in each size fraction. Exposures for multiple study populations were investigated using statistical analysis methods to test for associations with COVID-19-related outcomes, including the following.<br><br>UNLABELLED: &#x2022; COVID-19 cases (N = 773,374) and deaths (N = 14,311), by age, race, and sex, for 308 ZIP codes in Los Angeles County between June 19 and January 3, 2021. A negative binomial regression was performed for both individual and multiple ambient air pollutants to evaluate their associations with COVID-19 incidence and mortality.<br><br>UNLABELLED: &#x2022; Patients with COVID-19 who were admitted to Kaiser Permanente Southern California (KPSC) hospitals between June 1, 2020, and January 30, 2021 (N = 21,415). Cox proportional hazards models were used to evaluate associations between ambient air pollutant exposure and COVID-19 mortality. A subset was of KPSC patients with COVID-19 who received care exclusively in KPSC hospitals (N = 15,978). A multistate survival model was used to examine how air pollution affects the transition to recovery or deterioration to more severe COVID-19 states (e.g., intensive care admission or death). A subset was of KPSC patients with COVID-19 who maintained membership with KPSC for 1 year after hospital discharge (N = 12,634). We combined a set of 45 diagnoses of post-acute sequelae of SARS-CoV-2 (PASC) into categories based on organ systems and then studied a subset of these PASC categories that could be affected by air pollution, including cardiac, cardiometabolic, pulmonary, and neurological conditions. Logistic regression was used to evaluate associations between 30-day air pollution exposure before hospital admission and PASC conditions diagnosed at 3 months and 12 months post-discharge.<br><br>RESULTS: PM0.1, O3, NO2, and PM2.5 elemental carbon exposures were identified as risk factors for COVID-19 incidence and mortality in the general population of Los Angeles County. Air pollution exposures were also significantly associated with COVID-19 mortality in the cohort of hospitalized KPSC patients, controlling for other individual health risks. Incremental increases equivalent to the interquartile range for several pollution exposure concentrations were significantly associated with increased mortality, including PM2.5 mass (hazard ratio [HR], 1.12), PM0.1(HR, 1.06), PM2.5 nitrate (HR, 1.12), PM2.5 elemental carbon (HR, 1.07), PM2.5 on-road diesel (HR, 1.06), and PM2.5 on-road gasoline (HR, 1.07). Humidity and temperature in the month of diagnosis were significant negative predictors of COVID-19 mortality and negative modifiers of the air pollution effects. Results of the multistate analysis were consistent with these findings and further suggested that O3, NO2, and PM2.5 each were associated with deteriorating health states. Increased PM2.5 concentration was associated with increased risk of deterioration to both intensive care admission (HR, 1.16) and death (HR = 1.11). Effects of O3 were similar to those of PM2.5, but O3 also affected the transition from recovery to death (HR, 1.24). Several air pollutants - particularly O3, PM0.1, and PM2.5 nitrate - were significantly associated with several long COVID outcomes, including cardiac, cardiometabolic, and pulmonary conditions.<br><br>CONCLUSIONS: Broadly, we concluded that several common air pollutants are associated with COVID-19 incidence, mortality, and progression to more severe states of illness, including long COVID conditions. Air pollution is a modifiable environmental risk factor that could be altered to improve the prognosis of COVID-19, thereby also reducing the public health impacts of coronaviruses now and in the future. This is particularly important for preventing long COVID, as evidence suggests that PASC conditions can occur even in vaccinated individuals. Given that 10% to 30% of individuals with COVID-19 will experience some form of PASC, which can have lifelong debilitating effects,[5] the importance of addressing modifiable environmental risk factors, such as air pollution, cannot be underestimated. A recent Lancet editorial noted that societal investment in understanding the pathogenesis of long COVID and preventive measures has lagged well behind the levels needed to effectively treat and mitigate this complex disease.[6] Our research focused mostly on hospitalized patients, but it also included one study on the general population effects. The results of both analyses were generally concordant, although our most important findings likely apply only to patients hospitalized with COVID-19.},
}
@article {pmid41979291,
year = {2026},
author = {Abid, S and Jannath, H},
title = {Cardiac Effects in Post-COVID-19 Heart Failure: A Systematic Review of Longitudinal Imaging- and Biomarker-Based Structural and Functional Remodeling.},
journal = {Annals of cardiac anaesthesia},
volume = {29},
number = {2},
pages = {157-168},
pmid = {41979291},
issn = {0974-5181},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; Biomarkers/blood ; *Heart Failure/diagnostic imaging/physiopathology/etiology ; *Ventricular Remodeling/physiology ; Echocardiography ; Longitudinal Studies ; Magnetic Resonance Imaging ; },
abstract = {COVID-19 has been linked to persistent cardiovascular sequelae, yet the trajectory of structural and functional cardiac changes beyond the acute phase remains unclear. This systematic review synthesizes longitudinal evidence on post-COVID cardiac remodeling assessed by imaging and biomarkers. Following PRISMA guidelines, we searched PubMed and Cochrane Library (January 2020-April 2025) for peer-reviewed studies enrolling adults (≥18 years) with polymerase chain reaction (PCR)/antigen-confirmed SARS-CoV-2 infection and reporting cardiac outcomes ≥ 12 weeks post-infection. Eligible outcomes included imaging-based abnormalities (cardiac magnetic resonance [CMR]: T1/T2 mapping, late gadolinium enhancement [LGE]; echocardiography: left ventricular ejection fraction [LVEF], LV/RV strain). Longitudinal trends of biomarkers (troponin, NT-proBNP, C-reactive protein [CRP]) were also studied. Risk of bias was assessed using joanna briggs institute (JBI) tools; synthesis followed synthesis without metaanalysis (SWiM) principles. Fifteen studies (n ≈ 166,000; 14 cohorts, 1 case report) were included. Across CMR cohorts, global systolic function was largely preserved, but tissue abnormalities were frequent early and improved over time: edema indices normalized by ~ 12 months, while LGE prevalence declined (e.g. 50%→19% in paired scans). However, residual non-ischemic scars and elevated T1/T2 persisted in symptomatic subgroups. Echocardiography showed normal LVEF, but subtle left ventricular global longitudinal strain (LV-GLS) impairment versus controls (e.g. -18.5% vs - 19.3%). Biomarker trends were heterogeneous: natriuretic peptide positivity persisted in patients with prior cardiovascular disease (CVD), while troponin and CRP generally normalized. Large population-based cohorts demonstrated sustained 12-month risk for heart failure, myocarditis, and major cardiovascular events, graded by acute severity. Most patients recover gross systolic function, yet subclinical myocardial changes and elevated population-level cardiovascular risk persist up to 1 year. These findings support risk-stratified follow-up, judicious use of advanced imaging, and preventive cardiology strategies.},
}
@article {pmid41969525,
year = {2026},
author = {Abdullah, M and Naz, A and Reznikov, LR and Qureshi, JA and Hasnain, A and Obaid, A and Ali, A},
title = {Neuropeptide and cytokines expression in long COVID-19 related neuropsychological sequelae: insights into NK1R-mediated neuroinflammation and in silico therapeutic targeting.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1763029},
pmid = {41969525},
issn = {1662-5102},
abstract = {BACKGROUND: Long COVID-19 causes neurophysiological, cardiopulmonary, and musculoskeletal issues. Increased neuropeptides and cytokines lead to neuroinflammation, resulting in neurocognitive impairments, fatigue, depression, anxiety, and severe cognitive deficits. The Neurokinin 1 receptor (NK1R) is a cellular receptor for the neuropeptide Substance P, and its dysregulation links to neuropsychological issues despite antipsychotic use.<br><br>OBJECTIVES: In the present study, neuropsychological sequelae related to long COVID-19 were screened and the expression of related neuropeptides and cytokines was evaluated. Additionally, potential drugs have been evaluated computationally to reduce neuroinflammation in long COVID-19.<br><br>METHODS: After informed consent, subjects were screened by a medical physician for long COVID-19 in an outdoor patient clinic. Various biological scales were used to assess and categorize the severity of neuropsychological symptoms related to long COVID-19. After that, peripheral blood samples were collected from subjects using ELISA and RT-qPCR. Nine drugs were selected and subjected to virtual screening to identify potential drug antagonists for NK1R. The key drug-like properties, safety profile, pharmacokinetic analysis, and biological activity of the identified hits were assessed.<br><br>RESULTS: In this study the mean age of 90 patients (60% males and 40% females), was 33 &#xb1; 5 years in the symptomatic group and 31 &#xb1; 6 years in the asymptomatic long COVID-19 group for <40 years age-group. Whereas, the mean age of >40 years age-group was 58 &#xb1; 10 years in the symptomatic group and 54 &#xb1; 11 years in the asymptomatic long COVID-19 group. The minimum persistence of duration of long COVID-19 related symptoms in the <30 weeks group was observed to be 19 &#xb1; 6 weeks, while 44 &#xb1; 6 weeks in the >30 weeks group of symptomatic long COVID-19. A total of 48% patients had fatigue, 47% complained about headache, 28% had anxiety, 25% faced depression, 20% had psychosocial distress, 20% felt discomfort, and 13% had cognitive impairment. A total of 10% had reported dizziness sequelae among long COVID-19 survivors. Experimental data showed upregulation of IL-6, IL-10, and SP in both symptomatic and asymptomatic individuals compared with controls (p < 0.001). Drug screening analyses revealed aprepitant (-9.3 kcal/mol) and N- acetyl- L- tryptophan (-8.7 kcal/mol) stable interactions with NK1R and maintaining molecular dynamics stability (RMSD: 1.5-2.2 &#xc5;; RMSF 0.8-1.4 &#xc5;; Rg approximately 21.6 &#xc5;). These compounds also demonstrated favorable blood-brain barrier permeability and pharmacokinetic profiles, suggesting their potential as therapeutic antagonists for treating prolonged COVID-related neuroinflammation.<br><br>CONCLUSION: IL-6, IL-10, and SP are found to be deregulated in long COVID-19 leading to neurophysiological sequelae. To overcome neuropsychological sequelae, binding of SP to NK1R can be hindered using aprepitant and N-Acetyl-L tryptophan which has been evaluated computationally and may require further in vivo and in vitro studies for validation.},
}
@article {pmid41969541,
year = {2023},
author = {Northstone, K and Suarez-Perez, A and Matthews, S and Crawford, M and Timpson, NJ},
title = {The Avon Longitudinal Study of Parents and Children - a resource for COVID-19 research: questionnaire data capture July 2021 to December 2021, with a focus on long COVID.},
journal = {Wellcome open research},
volume = {8},
number = {},
pages = {292},
doi = {10.12688/wellcomeopenres.19596.2},
pmid = {41969541},
issn = {2398-502X},
abstract = {ALSPAC, the Avon Longitudinal Study of Parents and Children is a prospective population-based cohort study. Pregnant women were recruited in 1990-1992 and the study has followed them, their partners (Generation 0; G0) and their offspring (Generation 1; G1) for over 30 years. During the coronavirus 2019 (COVID-19) pandemic, ALSPAC deployed a series of online questionnaires to capture participant experiences during this unprecedented time. In July 2021, a fifth questionnaire was deployed which primarily focussed on the symptoms of long COVID, also known as post-COVID syndrome. G0 and G1 participants were offered both online and paper questionnaires between 21 [st] July 2021 and 11 [th] December 2021. Of 21,138 invitations, 11,148 (52.8%) participants returned the questionnaire (4,763 original mothers [mean age 59.1 years], 2,074 original fathers/partners [mean age 62.0 years] and 4,311 offspring [mean age 29.0 years]). Of these 11,148 participants, 2835 (25.4%) had not completed any of the previous COVID-19 questionnaires, while 3480 (31.2%) had returned all four previous questionnaires. In this questionnaire, 1077 participants (9.8%) reported a previous positive COVID-19 test over the course of the pandemic. Of these, 109 (1.0%) had received medical advice that they likely had COVID-19, and 838 (7.6%) suspected that they had had COVID-19. Almost a third of participants (n=796, 31.1%) reported possible long COVID (experiencing symptoms for at least 4 weeks), whilst 351 (13.7%) reported symptom duration of 12 weeks or more (post-COVID syndrome). G0 mothers were more likely to report a longer duration of symptoms compared to their partners and their children. The fifth COVID-19 questionnaire deployed by ALSPAC and the data obtained from are described in this data note.},
}
@article {pmid41971233,
year = {2026},
author = {Adebisi, YA},
title = {Prepandemic Risk Factors for Disabling Long COVID: A Prospective Cohort Analysis.},
journal = {Journal of tropical medicine},
volume = {2026},
number = {},
pages = {9396282},
pmid = {41971233},
issn = {1687-9686},
abstract = {INTRODUCTION: Disabling long COVID, characterised by persistent symptoms that limit daily functioning, has emerged as an important public health concern. However, prospective evidence on predisposing risk factors remains limited.<br><br>METHODS: This study used prospective data from the UK Household Longitudinal Study, linking prepandemic baseline information collected in Wave 10 (2018-19) with follow-up data from Wave 14 (2022-23). The analytic sample comprised 12,033 adults aged &#x2265;&#x2009;16&#x2009;years who participated in both waves and self-reported a positive COVID-19 test at follow-up. The primary outcome, disabling long COVID, was defined as symptoms lasting more than 12&#x2009;weeks that impaired day-to-day activities. Prepandemic sociodemographic, health and psychosocial factors assessed at baseline were included as predictors. Associations were estimated using modified Poisson regression with robust standard errors to calculate adjusted relative risks (RRs).<br><br>RESULTS: Disabling long COVID was reported by 690 individuals (5.7%). Higher risk was observed among women (RR 1.26; 95% CI 1.08-1.48) and adults aged 30-49 (RR 1.38; 95% CI 1.10-1.73) or 50-69 (RR 1.28; 95% CI 1.01-1.62) years, compared with those aged 16-29 years. Additional risk factors included pre-existing health conditions (RR 1.31; 95% CI 1.10-1.56), poor self-rated health (RR 1.78; 95% CI 1.40-2.25), psychological distress (RR 1.44; 95% CI 1.21-1.72) and poorer sleep quality (fairly bad: RR 1.92; 95% CI 1.45-2.56; very bad: RR 1.96; 95% CI 1.37-2.81), compared with very good sleep quality. Compared with non-White participants, White participants had lower risk (RR 0.75; 95% CI 0.61-0.92), while moderate (RR 0.76; 95% CI 0.62-0.93) and high (RR 0.81; 95% CI 0.67-0.98) income satisfaction, compared with low-income satisfaction, were protective. Stratified analyses showed that the effects of rural residence (p for interaction&#x2009;=&#x2009;0.011) and income satisfaction (p&#x2009;=&#x2009;0.009) differed significantly by sex, with weaker evidence for age (p&#x2009;=&#x2009;0.095) and self-rated health (p&#x2009;=&#x2009;0.061).<br><br>CONCLUSION: Prepandemic health, socioeconomic and psychological vulnerabilities were independently associated with disabling long COVID, with distinct sex-specific patterns of risk.},
}
@article {pmid41971988,
year = {2026},
author = {Ma, S and Koplin, E and Shilts, MH and Voehler, M and Rachakonda, G and Gil-Redondo, R and Rajagopala, SV and Sabaté Del Río, J and Botta-Orfila, T and Sibila, O and Asad, M and Sehanobish, E and Jerschow, E and Phillips, E and Millet, &#xd3; and Mallal, SA and Das, SR},
title = {A quantitative metabolic signature of host response during SARS-CoV-2 infection and recovery.},
journal = {iScience},
volume = {29},
number = {4},
pages = {115390},
pmid = {41971988},
issn = {2589-0042},
abstract = {COVID-19 has individualized disease trajectories during both acute infection and long-term recovery ("long COVID"), highlighting the need for biomarkers for the disease's heterogeneity. In this study, we introduce "metabo-time," a quantitative metabolic signature derived from serum metabolites and lipoproteins measured via nuclear magnetic resonance (NMR) spectroscopy. Metabo-time was stablished across two longitudinal and demographically diverse cohorts and validated in independent populations. It captures patient-specific metabolic states throughout the disease course. Longitudinally, it is disrupted during acute infection and normalizes during recovery, mirroring systemic oxidative stress and immune response dynamics. Importantly, metabo-time outperforms actual recovery time in predicting patients' individualized normalization of oxidative stress. At baseline, it distinguishes infection severity and is associated with transcriptional activity in the upper airway. These findings establish metabo-time as a robust marker for tracking COVID-19 heterogeneity and progression, with potential utility for stratifying patients and informing therapeutic strategies, particularly in the context of SARS-CoV-2 recovery.},
}
@article {pmid41972671,
year = {2026},
author = {Asaba, CN and Gwanyama, BN and Ayuk, HS and Odo, TI and Bitazar, R and Noumi, T and Labonté, P and Bukong, TN},
title = {Neutrophil Extracellular Traps in Viral Infections: Regulation, Immune Consequences, and Pathogenic Outcomes.},
journal = {Cells},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/cells15070580},
pmid = {41972671},
issn = {2073-4409},
support = {Relance 2024//The INRS-Armand-Frappier Sant&#xe9; Biotechnologie Research Centre/ ; 363424//A doctoral scholarship from the Fonds de Recherche du Qu&#xe9;bec./ ; },
mesh = {*Extracellular Traps/immunology ; Humans ; *Neutrophils/immunology ; *Virus Diseases/immunology/pathology ; Animals ; COVID-19/immunology ; SARS-CoV-2/immunology ; Immunity, Innate ; Signal Transduction ; },
abstract = {Neutrophils are among the early responders of the innate immune system and play a key role in host defense against viral infections. Beyond their classical antimicrobial functions, neutrophils can engage in a specialized defense mechanism by releasing web-like extracellular DNA known as neutrophil extracellular traps (NETs). These extracellular traps are a mesh-like network of chromatin DNA decorated with cellular components, including histones, proteases, and antimicrobial enzymes, that function to contain and limit the spread of pathogens. While NET formation contributes to antiviral immunity, accumulating evidence indicates that excessive or dysregulated NET formation can significantly contribute to immunopathology during viral infections. Thus, depending on the context and outcome, NET formation may be viewed as a double-edged sword. Therefore, understanding the regulatory mechanisms governing NET formation and its harmful effects is critical for developing therapeutic strategies that enhance antiviral defense while minimizing tissue damage. In this review, we provide a comprehensive overview of the molecular mechanisms that drive NET formation and clearance, with a particular focus on how viruses modulate these processes to influence disease outcome. We also discuss the pathways underlying NET formation and subsequent neutrophil cell death (NETosis), including canonical and non-canonical pathways, and highlight key signaling axes involving SYK, MAPKs, and NF-κB. Using SARS-CoV-2 and hepatitis B virus as representative models, we examine how different viral components trigger, exploit, or evade NET targeting and how persistent accumulation of NETs can contribute to hyperinflammation, progressive tissue injury, and post-viral syndromes. We further explore emerging evidence linking impaired NET clearance and neutrophil heterogeneity, particularly low-density neutrophils (LDNs), to chronic inflammation and post-viral sequelae such as long COVID and autoimmune hepatitis. Finally, we summarize current and emerging therapeutic strategies aimed at modulating NET formation or enhancing NET clearance. Altogether, this review underscores the dual nature of NETs in viral infections, highlighting their potential roles in antiviral defense and tissue injury, and provides a framework for the development of targeted interventions to limit virus-induced immunopathology.},
}
@article {pmid41973314,
year = {2026},
author = {Peddireddy, S and VanWingerden, N and Patel, P and Howard, G and Berger, J},
title = {Stellate Ganglion Block in the Treatment of Long COVID: A Systematic Review.},
journal = {Current pain and headache reports},
volume = {30},
number = {1},
pages = {},
pmid = {41973314},
issn = {1534-3081},
mesh = {Humans ; *Stellate Ganglion ; *COVID-19/complications/therapy ; *Autonomic Nerve Block/methods ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVES: This review evaluates stellate ganglion block as a treatment for long COVID, seeking to evaluate the treatment's efficacy by various symptoms and the limitations of the current literature.<br><br>STUDY DESIGN: Systematic Review.<br><br>SETTING: Ambulatory or Outpatient Setting.<br><br>METHODS, SUBJECTS: A systematic review of the current literature regarding use of stellate ganglion block in patients with long COVID was conducted. 2 databases were searched on August 28th, 2025. Search terms were "long COVID" and "stellate ganglion block", yielding 45 results. Studies examining patient outcomes after stellate ganglion block were included. Case reports, case series, basic science studies and previous reviews were excluded. Seven studies met inclusion criteria.<br><br>RESULTS: Patients received a single stellate ganglion block in some studies and multiple stellate ganglion blocks in others. All studies reported symptomatic improvement without control groups. Response rates ranged from 55.8% to 100%. The most robust improvements (>&#x2009;80% patients reporting relief) were seen in cough, dyspnea, headache, joint pain, pain interference/intensity, pins/needles, subjective relief.<br><br>CONCLUSION: Stellate ganglion block is a promising treatment that appears to generate substantive benefit for many of the symptoms seen in long COVID. However, the current literature has small, uncontrolled studies with heterogenous study designs and follow-up periods. Standardized research with larger sample sizes, control groups, and longer-term follow up is necessary to elucidate the degree of benefit. IRB approval and clinical trial registration not required.},
}
@article {pmid41973786,
year = {2026},
author = {O'Loughlin, KM and Herring, TE and Gentile, NL and Bender, JA and Friedly, JL and Knowles, LM},
title = {Correlates of patient interest in rehabilitation psychology services among individuals with long COVID: A cross-sectional analysis.},
journal = {Rehabilitation psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/rep0000671},
pmid = {41973786},
issn = {1939-1544},
support = {/HS/AHRQ HHS/United States ; },
abstract = {PURPOSE/OBJECTIVE: Long COVID is a complex chronic condition, affecting approximately 18% of adults in the United States and commonly involves fatigue, cognitive impairment, pain, and psychiatric conditions (e.g., depression, anxiety, posttraumatic stress disorder, and insomnia). Despite high psychiatric burden, many individuals do not receive mental health care, and little is known about their interest in psychological services. This study characterized symptom profiles of long COVID and examined correlates of patients' interest in rehabilitation psychology services.<br><br>RESEARCH METHOD/DESIGN: Secondary data analysis of routinely collected clinical data. Descriptive statistics were calculated, and logistic regression analyses examined associations of interest.<br><br>RESULTS: Participants in the full sample (N = 1,789) were predominantly White, non-Hispanic, and female, with high rates of fatigue (84.9%), cognitive difficulties (55.3%-74.3%), and psychiatric history (51.8%). Over half (56.8%) expressed interest in rehabilitation psychology services, including individual (50.2%) and group (32.1%) formats. Two participants were excluded from regression analyses due to sparse cell size, yielding a final analytic sample of n = 1,787. Interest in individual services was associated with not having a mental health provider, greater depression and anxiety, poor sleep, and lower cognitive functioning. Interest in group services was associated with psychiatric history, greater anxiety, lower cognitive and social functioning, and better physical functioning.<br><br>CONCLUSION/IMPLICATIONS: Anxiety symptoms and cognitive difficulties are key correlates of interest in rehabilitation psychology services, underscoring the value of early screening and targeted intervention. Stigma and prioritization of medical concerns may limit engagement, highlighting the importance of psychoeducation and stigma-reduction efforts to support engagement in care. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}
@article {pmid41975034,
year = {2026},
author = {Matthews, R and Alam, A and Bullmore, E and Michael, BD},
title = {Understanding the long-term neurological effects of SARS-CoV-2 infection.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {41975034},
issn = {1759-4766},
abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a heterogeneous condition marked by persistent symptoms following acute SARS-CoV-2 infection. As approximately 6% of people who have experienced acute COVID-19 are estimated to develop PCC, the potential population is vast. Many of the key symptoms of PCC reflect involvement of the nervous system, ranging from cognitive impairment ('brain fog'), headaches and fatigue to anxiety and depression. This Review summarizes the spectrum of neurological and psychological symptoms that occur following acute SARS-CoV-2 infection, with a particular focus on the international consensus-based core outcome set for PCC. We also explore the proposed underlying mechanisms, including evidence for immune system dysregulation, microvascular dysfunction and volumetric changes on neuroimaging. In addition, we review ongoing and completed large-scale treatment trials. Growing evidence suggests a bidirectional interaction between symptoms traditionally considered neurobiological in origin, such as cognitive deficits and headache, and those within the purview of psychiatry, such as anxiety and depression. PCC represents an opportunity to better understand the long-term consequences of acute infection and improve management strategies and outcomes, not only for people with the condition but also for those with other post-viral syndromes that affect brain health.},
}
@article {pmid41975235,
year = {2026},
author = {Bansal, A and Olechnowicz, SWZ and Kiernan-Walker, N and Cumming, J and Abdul Azeez, I and Mazhari, R and , and Cox, RJ and Mueller, I and Bowden, R and Eriksson, EM},
title = {Divergent inflammatory and neurology-related protein levels in long COVID following primary and breakthrough SARS-CoV-2 infections.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01541-6},
pmid = {41975235},
issn = {2730-664X},
abstract = {BACKGROUND: Long COVID is a complex condition where symptoms persist for more than 3 months after SARS-CoV-2 infection and affects an estimated 5-30% of individuals. While persistent inflammation has emerged as an important feature of this condition, it is unclear if immune responses from COVID-19 vaccination or SARS-CoV-2 re-infection exacerbate or mirror the initial inflammatory responses.<br><br>METHODS: We quantified 182 inflammatory and neurology-related proteins in plasma using multiplexed affinity proteomics. Plasma samples from the COVID PROFILE cohort conducted in Victoria, Australia, were collected 6-9 months after first infection, but before COVID-19 vaccination from individuals who had recovered from COVID-19 (n&#x2009;=&#x2009;21) or from individuals with long COVID (n&#x2009;=&#x2009;12). To establish baseline plasma profiles, protein levels were benchmarked against unvaccinated, SARS-CoV-2 naive individuals (n&#x2009;=&#x2009;24). In addition, we performed longitudinal analysis in a subset of individuals (n&#x2009;=&#x2009;34), where paired samples collected 2-4 weeks after a third COVID-19 vaccine dose and after SARS-CoV-2 breakthrough infection were available to assess inflammatory and neurology protein plasma levels after antigen exposure in these contexts.<br><br>RESULTS: In this cohort Boruta feature selection and lasso regression models identified IL-20, HAGH, NAAA, CLEC10A, LXN, and MCP-1, TRAIL, G-CSF, NBL1, and CCL23 as best discriminating proteins when comparing the long COVID group to groups of either healthy or COVID-19 recovered. Notably, longitudinal analysis indicated differences in the levels of a subset of plasma proteins following primary infection compared to after COVID-19 booster vaccination and breakthrough infection within the groups.<br><br>CONCLUSIONS: These findings suggest that there is an altered immune response outcome primarily observed in individuals with long COVID upon re-exposure.},
}
@article {pmid41965722,
year = {2026},
author = {Magnúsdóttir, I and Nygaard, AB and Hoffart, A and Murphy, G and Kõiv, K and Barker, MM and Lovik, A and Unnarsdóttir, AB and Kähler, AK and Hauksdóttir, A and Thordardottir, EB and Eyþórsson, E and Gísladóttir, EU and Joyce, EE and Frans, EM and Tómasson, G and Hjördísar Jónsdóttir, HL and Rúnarsdóttir, H and Harðardóttir, H and Dahl, JA and Jakobsdóttir, J and Kalleberg, KT and Ásbjörnsdóttir, KH and Ellingjord-Dale, M and Istre, MS and Landrø, NI and Shen, Q and Bø, R and Mägi, R and Pálsson, R and Brunvoll, SH and Johnson, SU and Søraas, A and Fang, F and Lehto, K and Ebrahimi, OV and Aspelund, T and Valdimarsdóttir, UA},
title = {Acute COVID-19 severity and impaired cognitive function up to 32 months after diagnosis: an observational study.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04856-2},
pmid = {41965722},
issn = {1741-7015},
support = {2022-00597//Forskningsr&#xe5;det f&#xf6;r h&#xe4;lsa, arbetsliv och v&#xe4;lf&#xe4;rd/ ; PSG615//Eesti Teadusagentuur/ ; 138929//NordForsk/ ; 847776//Horizon 2020/ ; },
abstract = {BACKGROUND: Cognitive dysfunction ("brain fog") is a commonly reported post-COVID-19 symptom. Leveraging data from five general population cohorts across four European countries (Estonia, Iceland, Norway, and Sweden), we assessed long-term prevalence of impaired subjective cognitive function among individuals diagnosed with COVID-19 by acute illness severity.<br><br>METHODS: The included cohorts consisted of adult participants recruited from March 2020 and followed with self-report measures of cognitive function and past COVID-19 infection (except one cohort consisting of clinically confirmed COVID-19 cases) through February 2023. In a cross-sectional analysis we contrasted the prevalence of impaired cognitive function among individuals with and without a COVID-19 diagnosis, overall and by illness severity up to 32&#xa0;months post-diagnosis. We adjusted for age, gender, education, relationship status, binge drinking, body mass index, previous psychiatric diagnosis, number of chronic medical conditions, and response period. In a longitudinal analysis, we assessed potential changes in cognitive function scores before and after COVID-19 diagnosis.<br><br>RESULTS: The study population consisted of 153,841 participants (71% women), with 31,359 (20.4%) reporting a positive COVID-19 test. Overall, a COVID-19 diagnosis was not statistically significantly associated with increased prevalence ratio (PR) of impaired cognitive function (PR 1.30 [95% CI: 0.98-1.71]). Individuals bedridden due to COVID-19 for 1-6&#xa0;days (PR 1.38 [95% CI 0.96-1.99]) or&#x2009;&#x2265;&#x2009;7&#xa0;days (2.59 [1.55-4.33]) had higher prevalence of impaired cognitive function compared to those never diagnosed, while individuals never bedridden had a lower prevalence to those never diagnosed with COVID-19 (0.89 [0.80-1.00]). These findings were corroborated in the longitudinal analysis where a pre- to post diagnosis decline in cognitive function was observed among individuals bedridden due to COVID-19 (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: The data indicates that a severe COVID-19 acute illness course is associated with impaired cognitive function up to 18-32&#xa0;months after COVID-19 diagnosis.},
}
@article {pmid41965729,
year = {2026},
author = {Springe, ML and Vaivode, K and Saksis, R and Vainšeļbauma, NM and Ansone, L and Brīvība, M and Niedra, H and Rovite, V},
title = {Immune dysregulation in prolonged Long-COVID: lymphocytes emerge as key mediators of persistent inflammation, exhaustion and cytotoxicity.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08081-6},
pmid = {41965729},
issn = {1479-5876},
abstract = {BACKGROUND: Long-COVID affects at least 10% of COVID-19 survivors, displaying debilitating symptoms across multiple organ systems. Despite the widespread prevalence, Long-COVID aetiology remains poorly understood, but emerging evidence points to immune dysregulation as a potential mechanism involved in its development or persistence.<br><br>METHODS: This study presents a unique analysis of the peripheral blood mononuclear cell transcriptomic profile of COVID-19 and Long-COVID patients at single-cell resolution. We reconstructed the cell state and intercellular communication using differentially expressed gene profiling and ligand-receptor interaction analyses.<br><br>RESULTS: Our results reveal altered T and natural killer cell subset proportions, diminished proliferating lymphocyte and B cell signalling capacity, and the expression of exhaustion and cytotoxicity associated genes 1.5-2&#x2009;years post-infection, suggesting incomplete immune recovery. Distinct interferon responses in these cell populations at the acute phase for patients who go on to develop Long-COVID indicate early disease mediator potential.<br><br>CONCLUSIONS: Collectively, these findings provide insight into the immune processes underlying the progression of COVID-19 into a chronic Long-COVID state. The observed changes in immune cell subsets at the acute phase of the infection may be predictive of Long-COVID progression and could be useful in understanding disease aetiology while the observed long-term effects are crucial to developing therapeutic and diagnostic tools.},
}
@article {pmid41966515,
year = {2026},
author = {Gardiner, LE and Lozano-Rojas, D and Smith, N and Espley, J and Stewart, ID and Ntotsis, K and Aul, R and Bakerly, ND and Beirne, P and Bolton, CE and Brown, JS and Briggs, A and Chalder, T and Chalmers, JD and Choudhury, G and Davies, MJ and De Soyza, A and Docherty, AB and Easom, N and Echevarria, C and Efstathiou, CM and Elneima, O and Fuld, J and Geddes, JR and Goemans, AF and Greenhalf, W and Greening, NJ and Guillen-Guio, B and Harris, VC and Harrison, EM and Hart, N and Heaney, LG and Heller, S and Ho, LP and Horsley, A and Houchen-Wolloff, L and Howard, L and Hurst, JR and Iqbal, MM and Jacob, J and Jenkins, RG and Jolley, C and Jones, M and Kerr, S and Khunti, K and Leavy, OC and Lewis, K and Lone, NI and Lord, JM and Man, WD and Marks, M and McAuley, HJC and McCann, GP and Neubauer, S and Openshaw, PJ and Parekh, D and Pfeffer, P and Poinasamy, K and Porter, JC and Quint, JK and Rahman, NM and Raman, B and Richardson, M and Rowland-Jones, SD and Rowland, MJ and Saunders, RM and Scott, JT and Semple, MG and Sereno, M and Shah, AM and Sheikh, A and Shikotra, A and Singapuri, A and Taquet, M and Thomas, D and Thompson, AAR and Thorpe, M and Toshner, M and Wang, L and Wootton, DG and Zheng, B and Wain, LV and Brightling, CE and Singh, SJ and Taylor, RS and Evans, RA and , },
title = {Investigating prognostic classifications of pre-existing multiple long-term conditions for health outcomes one-year after COVID-19 hospitalisation: a UK prospective observational study.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108695},
doi = {10.1016/j.ijid.2026.108695},
pmid = {41966515},
issn = {1878-3511},
abstract = {BACKGROUND: Pre-existing multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how pre-existing MLTCs, including different categorisation and patterns of MLTCs, affect one-year health outcomes after severe COVID-19.<br><br>METHODS: Adults post-hospitalisation following COVID-19 were recruited during 2020 -2021. We compared recovery at one-year after discharge using adjusted multivariable logistic regression in 1:1 propensity matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without pre-existing MLTCs. In adults with MLTCs, different categorisation such as number of conditions, number and types of body systems involved (e.g., respiratory, cardiovascular), and latent class analysis derived patterns of condition co-occurrence were assessed for their association with recovery at one-year.<br><br>FINDINGS: 647 adults with MLTCs were matched with 647 adults without MLTCs (n=1294; 61.9% male, 79.6% of white ethnicity, median age 59 [IQR 52-67] years). The presence of MLTCs were associated with lower odds of feeling fully recovered (odds ratio (OR) 0.66 [95% CI 0.51 to 0.85], p=0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g., respiratory (OR 0.49 [95% CI 0.34 to 0.69], p<0.001)) but not by the number of conditions (p>0.1). Four latent classes of MLTCs co-occurrence were estimated with different risks of recovery (p<0.01).<br><br>INTERPRETATION: Adults with pre-existing MLTCs were 34% less likely to feel fully recovered at one-year after COVID-19 hospitalisation compared with adults without MLTCs. We describe prognostic classifications of MLTCs with future work needed to understand if they have prognostication in broader post-acute infection sequalae.},
}
@article {pmid41966782,
year = {2026},
author = {Shi, H and Zhang, Y and Yao, Z and Song, W and Xu, X and Tang, X and Cui, L and Song, H and Shu, R and Wang, J and You, X},
title = {Aminopeptides ameliorate long COVID symptoms in immunocompromised rheumatic patients through immune reconstitution.},
journal = {International immunopharmacology},
volume = {179},
number = {},
pages = {116630},
doi = {10.1016/j.intimp.2026.116630},
pmid = {41966782},
issn = {1878-1705},
abstract = {OBJECTIVE: To evaluate the effects of aminopeptide nutritional support on immune reconstitution and antiviral capacity in immunocompromised patients with rheumatic diseases.<br><br>METHODS: This single-center, retrospective cohort study included patients with rheumatic diseases and concomitant immunocompromised conditions who received treatments at the outpatient department of Peking Union Medical College Hospital between December 2021 and October 2024. Participants were divided into an experimental group (aminopeptide supplementation) and a control group according to whether they received aminopeptide treatment, with a treatment duration of 2-3&#xa0;months. Data regarding SARS-CoV-2 virus infection, specific Long COVID symptoms, and outcomes were collected via questionnaire. TB lymphocyte subsets were recorded before and after treatment or at 3-6-month intervals.<br><br>RESULTS: A total of 171 patients with rheumatic diseases were enrolled, including 102 in the experimental group and 69 in the control group. Eighty-eight patients exhibited Long COVID symptoms, with fatigue being the most prevalent (67%). The experimental group showed a significantly higher rate of Long COVID symptom remission compared to the control group (64.2% vs. 22.9%), with a notable improvement in fatigue (68.3% vs. 27.8). Significant post-treatment increases were observed in peripheral blood CD3[+] T cells and CD8[+] T cells. Multivariate logistic regression analysis indicated that aminopeptide supplementation increased the rate of Long COVID symptom remission by 8.46-fold and the rate of fatigue improvement by 9.19-fold.<br><br>CONCLUSION: Supplementation with aminopeptides may improve nutritional status and enhance TB lymphocyte subsets levels in immunocompromised patients with rheumatic diseases, potentially contributing to better antiviral immunity and alleviation of Long COVID symptoms.},
}
@article {pmid41967005,
year = {2026},
author = {Iskander, JK and Haridopolos, S},
title = {Making Invisible Illnesses Visible: Recognizing and Responding to Infection Associated Chronic Conditions.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag240},
pmid = {41967005},
issn = {1537-6591},
abstract = {The emergence of post-COVID conditions (PCC) has renewed attention to infection-associated chronic conditions and illnesses (IACCI), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Lyme disease-associated chronic symptoms. Millions of Americans are affected by these debilitating, misunderstood conditions, which share symptom profiles and pathophysiologic abnormalities. IACCI have received insufficient clinical attention and research investment. We outline elements of a patient-centered approach to care, emphasizing validation of patients' experiences, multidisciplinary management, and symptom-focused treatment. Opportunities to strengthen clinical practice include a new CMS code for chronic condition management, extended visits, and creation of welcoming care environments. Advances in PCC and ME/CFS research provide a foundation for exploring shared mechanisms and developing targeted therapies. Improved surveillance, harmonized research, and inclusive trial designs are needed to define disease burden and accelerate therapeutic progress. Coordinated action by clinicians, researchers, and policymakers can help address longstanding gaps and improve outcomes for all individuals with IACCI.},
}
@article {pmid41964305,
year = {2026},
author = {Rosemberg, MS and Park, S},
title = {Covid Is Gone but Not Fully: Addressing Long Covid Among Workers.},
journal = {Workplace health &amp; safety},
volume = {},
number = {},
pages = {21650799261434057},
doi = {10.1177/21650799261434057},
pmid = {41964305},
issn = {2165-0969},
}
@article {pmid41958356,
year = {2026},
author = {Bohlin, J and Lee, Y and Caspersen, IH and Hayman Robertson, A and Page, CM and Gjessing, HK and Jugessur, A and Magnus, P and Mjaaland, S and Trogstad, L},
title = {Longitudinal study of genome-wide DNA methylation in individuals with and without post-acute symptoms following SARS-CoV-2 infection.},
journal = {Epigenomics},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17501911.2026.2656361},
pmid = {41958356},
issn = {1750-192X},
abstract = {BACKGROUND: Symptoms following SARS-CoV-2 infection, referred to as Long-COVID, have been reported since the pandemic. We investigated whether COVID-19 or Long-COVID is associated with persistent genome-wide DNA methylation (DNAm) changes in whole blood using a longitudinal design.<br><br>METHODS: DNAm was measured using the Illumina EPIC V2 platform (859,651 CpGs) in 297 adult participants (594 samples in total) from two Norwegian population-based cohorts, with samples collected pre-infection (2020) and during the pandemic (2023). Participants were classified as Long-COVID, COVID-19 (no persistent symptoms), or not infected.<br><br>RESULTS: No significant DNAm differences were observed between Long-COVID and not infected at either time point (p&#x2009;=&#x2009;0.745(FDR)) or during the pandemic specifically (p&#x2009;=&#x2009;0.629(FDR)). Likewise, no differences were detected between COVID-19 and not infected across both time points (p&#x2009;=&#x2009;0.883(FDR)) or during the pandemic (p&#x2009;=&#x2009;0.287(FDR)). Sex-stratified analyses of the X chromosome revealed no significant DNAm differences for Long-COVID or COVID-19 in males (both p&#x2009;=&#x2009;0.999(FDR)) or females (both p&#x2009;=&#x2009;0.999(FDR)). Epigenetic age acceleration was also evaluated using DunedinPACE (DP) and PhenoAge (PA), but no significant differences were detected for Long-COVID (p&#x2009;=&#x2009;0.695 [DP], p&#x2009;=&#x2009;0.528 [PA]) or COVID-19 (p&#x2009;=&#x2009;0.624 [DP], p&#x2009;=&#x2009;0.348 [PA]).<br><br>CONCLUSION: No persistent epigenetic age- or DNAm based differences due to Long-COVID or SARS-CoV-2 infection were detected in our cohorts.},
}
@article {pmid41959563,
year = {2026},
author = {Waters, M and Vlok, M and Kroon, EE and Kotze, MJ and Moremi, KE and Oladejo, SO and Rajaratnam, K and Nunes, JM and Venter, C and Scott, CJ and Kell, DB and Pretorius, E},
title = {Proteomic signatures of COVID-19 Post-Vaccination/Post-Infection Syndrome (PV/PIS): insights into immune dysregulation and coagulopathy.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1753348},
pmid = {41959563},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/blood ; Proteomics ; Male ; *COVID-19 Vaccines/adverse effects ; Middle Aged ; Female ; SARS-CoV-2/immunology ; *Vaccination/adverse effects ; Adult ; Aged ; *Blood Coagulation Disorders/etiology ; *Proteome/analysis ; Chromatography, Liquid ; Post-Infectious Disorders ; },
abstract = {INTRODUCTION: During the global rollout of COVID-19 vaccines, a subset of individuals reported persistent symptoms following vaccination, with clinical presentations overlapping those of Long COVID and requiring individualised treatment strategies. Distinguishing between vaccine-related adverse events and post-infectious sequelae is challenging, particularly given the potential for unrecognised asymptomatic or mild SARS-CoV-2 infection before or after vaccination. To address this complexity, we defined our disease cohort as individuals experiencing persistent symptoms (≥ 12 weeks) following SARS-CoV-2 vaccination, without a confirmed history of prolonged symptoms after acute infection; for clarity, we refer to this group as presenting with Post-Vaccination/Post-Infection Syndrome (PV/PIS).<br><br>METHODS: In this study, we conducted a plasma proteomic analysis of digested microclot deposits isolated from platelet-poor plasma samples of 14 individuals with PV/PIS compared to 16 healthy controls, using liquid-chromatography-mass spectrometry.<br><br>RESULTS: We identified significant alterations in coagulation factors, acute phase proteins, and immune response modulators in the PV/PIS group compared to controls. Notably, elevated levels of serum amyloid A1 and A2, attractin, and coagulation factors X and XI were observed, alongside downregulation of immune-regulatory proteins. These findings suggest that PV/PIS is characterised by persistent immune dysregulation and coagulopathy.<br><br>CONCLUSIONS: This proteomic signature was found to only partially overlap with that previously reported in a proteomics analysis on Long COVID samples, collected prior to vaccination availability. Our results highlight the complex interplay between immune activation, endothelial dysfunction, and coagulation pathologies in PV/PIS, with distinct differences detected between these systems in Long COVID and PV/PIS, paving the way for more targeted protein research in these conditions.},
}
@article {pmid41960594,
year = {2026},
author = {Leverty, R and Sutton, S and Jackson, C and Cerda, M and Chang, A and Zimmerman, K},
title = {Engaging patients and researchers in RECOVER clinical trial protocol development: Key lessons.},
journal = {Journal of clinical and translational science},
volume = {10},
number = {1},
pages = {e49},
pmid = {41960594},
issn = {2059-8661},
abstract = {The RECOVER Clinical Trials Protocol Working Groups (PWGs) were established to rapidly design trials addressing Long COVID by incorporating the complementary expertise of researchers, clinicians, and patients, caregivers, and community representatives (Representatives). This paper explores the engagement of Representatives in protocol development, highlighting their contributions, challenges faced, and lessons learned. A survey of PWG members revealed that while most Representatives felt their input was valued, gaps in role clarity, communication, and integration of feedback persisted. Representatives emphasized the importance of understanding patient burden and lived experience, while researchers and project leaders noted the value of inclusive perspectives. Findings underscore the need for structured engagement practices, clear expectations, and ongoing support to ensure meaningful participation. These insights offer a roadmap for future clinical trial networks seeking to integrate patient voices in research design.},
}
@article {pmid41962975,
year = {2026},
author = {Dai, Y and Luo, H and Liu, X and Hu, BM and Wang, M and Cheng, LX and Luo, Y and Ma, XY and Cao, G and Mao, Q and Li, L},
title = {Health outcomes and reinfection among COVID-19 survivors 4 years after hospital discharge in Wuhan, China: a cohort study.},
journal = {BMJ open},
volume = {16},
number = {4},
pages = {e113446},
doi = {10.1136/bmjopen-2025-113446},
pmid = {41962975},
issn = {2044-6055},
mesh = {Humans ; Male ; *COVID-19/epidemiology/complications ; Middle Aged ; China/epidemiology ; Female ; Longitudinal Studies ; Risk Factors ; Patient Discharge ; Aged ; *Reinfection/epidemiology ; SARS-CoV-2 ; Fatigue/epidemiology ; *Survivors/statistics &amp; numerical data ; Adult ; Anxiety ; Depression/epidemiology ; },
abstract = {OBJECTIVES: To evaluate health outcomes and identify risk factors for reinfection and persistent symptoms among COVID-19 survivors 4 years after hospital discharge.<br><br>DESIGN: Longitudinal cohort study.<br><br>SETTING: Two hospitals in Wuhan, China.<br><br>PARTICIPANTS: 1076 COVID-19 survivors discharged from hospital.<br><br>OUTCOME MEASURES: Self-reported symptom questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test, Hospital Anxiety and Depression Scale and Checklist Individual Strength (CIS) fatigue subscale. Long covid was defined according to WHO criteria.<br><br>RESULTS: Median age was 58 years and 50.2% were male. Reinfection during December 2022-April 2023 occurred in 36.1%; 21 developed pneumonia and 14 required hospitalisation. At least 12 months after reinfection, 12.1% reported sequelae compared with 46.9% after the initial infection. At 4 years, 16.7% reported long covid symptoms, commonly fatigue, chest tightness, cough and dyspnoea. In multivariable analysis, risk factors for abnormal fatigue (CIS &#x2265;27) included age (OR 1.020, 95%&#x2009;CI 1.007 to 1.034; p=0.003), reinfection (OR 2.393, 95%&#x2009;CI 1.708 to 3.352; p<0.001), severe disease (OR 1.553, 95%&#x2009;CI 1.088 to 2.218; p=0.015) and tumour (OR 3.420, 95%&#x2009;CI 1.177 to 9.936; p=0.024).<br><br>CONCLUSIONS: At 4 years post discharge, symptom burden was lower than at earlier follow-up time points for most survivors. Reinfection and older age were associated with persistent symptoms.},
}
@article {pmid41952397,
year = {2026},
author = {Mavroudis, P and Ragia, G and Pantazis, N and Dermitzaki, E and Stamati, A and Pallikarou, M and Velentza, L and Paflioti, E and Zarkotou, O and Gerakari, S and Giannitsioti, E and Gravanis, A and Manolopoulos, VG},
title = {Association of ADIPOQ rs1501299 with long-COVID syndrome: a single-center cross-sectional study.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2654244},
doi = {10.1080/07853890.2026.2654244},
pmid = {41952397},
issn = {1365-2060},
mesh = {Humans ; *Adiponectin/genetics/blood ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Polymorphism, Single Nucleotide ; *COVID-19/genetics/complications/blood ; Adult ; SARS-CoV-2 ; Aged ; Genetic Predisposition to Disease ; Genotype ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long-COVID syndrome is a public health issue, affecting millions of individuals worldwide. However, the pathophysiological mechanisms underlying the syndrome's sequelae are still under investigation. Adiponectin has been implicated with acute SARS-CoV2 infection, while its role in Long-COVID remains obscure. The aim of this study is to investigate the potential association of adiponectin and SNPs of adiponectin pathway with Long-COVID.<br><br>MATERIALS AND METHODS: A single-center cross-sectional observational study was conducted, investigating the potential association of adiponectin and SNPs of adiponectin pathway with Long-COVID in 159 individuals, who were presented at the COVID-19 outpatient re-evaluation office. Adiponectin blood levels and detection of SNPs ADIPOQ rs1501299, ADIPOQ rs2241766, ADIPOR2 rs16928751, PPARA rs1800206 and PPARG rs1801282 were measured 3&#x2009;months after acute COVID-19.<br><br>RESULTS: ADIPOQ rs1501299 was the only SNP significantly associated with the progression of symptoms after the acute SARS-CoV2 infection and the development of Long-COVID syndrome. Homozygous GG genotype individuals exhibited increased risk for sequelae of Long-COVID (OR 2.0, 95% CI 1.1, 3.7, p&#x2009;=&#x2009;0.023), particularly fatigue (OR 2.4, 95% CI 1.2, 5.0, p&#x2009;=&#x2009;0.014), compared to the T allele carriers, independently of age, sex, BMI, waist to hip ratio, comorbidities and severity of acute infection (OR 2.2, 95% CI 1.2, 4.3, p&#x2009;=&#x2009;0.013 and OR 3.1, 95% CI 1.4, 6.7, p&#x2009;=&#x2009;0.004 respectively). Adiponectin levels were correlated with obesity and severity of acute SARS-CoV2 infection, but not with Long-COVID symptoms.<br><br>CONCLUSION: ADIPOQ rs1501299 could potentially serve as a genetic marker, contributing to risk stratification of developing Long-COVID syndrome.},
}
@article {pmid41953516,
year = {2026},
author = {Qu, HQ and Kao, C and Hakonarson, H},
title = {Redefining the role of the thiol-based agent N-acetylcysteine in human health and disease and elucidating potential advantages of its amide derivative.},
journal = {RSC medicinal chemistry},
volume = {},
number = {},
pages = {},
pmid = {41953516},
issn = {2632-8682},
abstract = {N-Acetylcysteine (NAC) is the established antidote for acetaminophen toxicity and an approved mucolytic agent. Beyond these traditional uses, increasing evidence highlights its broader role as a modulator of thiol-redox biology. Rather than functioning as a nonspecific antioxidant, NAC modulates glutathione metabolism, redox-sensitive signaling, immune checkpoints, thiol-based post-translational modifications, ferroptosis susceptibility, and glutamatergic neurotransmission. This review synthesizes mechanistic, preclinical, and clinical evidence across pulmonary, hepatic, neuropsychiatric, metabolic, cardiovascular, and oncologic disorders, emphasizing how variability in baseline redox state, pharmacogenetics, and delivery contributes to heterogeneous outcomes. Strategies to improve pharmacokinetics and tissue targeting include structural derivatives such as N-acetylcysteine amide (NACA), and combination regimens such as NAC with probenecid or GlyNAC. Emerging applications span long COVID, neurodegeneration, psychiatric disorders, microbiome-redox interactions, environmental toxicology, and cancer immunotherapy. NAC and NACA exemplify the evolution of redox-targeted therapeutics. NAC is well established for safety and clinical utility, but its pharmacokinetic and tissue distribution properties constrain broader efficacy. NACA, a lipophilic amide derivative, enhances membrane permeability and cellular uptake, suggesting it may achieve higher tissue exposure at lower doses. Future progress will rely on biomarker-guided, precision approaches that optimize dosing, formulation, and delivery while exploring rational combinations across disease contexts defined by redox biology.},
}
@article {pmid41955274,
year = {2026},
author = {Wu, D and Dasgupta, A and Hora, JS and Chen, KH and Banerjee, A and Archer, SL},
title = {SARS-CoV-2 targets mitochondria, exacerbating COVID-19 pneumonia.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP290297},
pmid = {41955274},
issn = {1469-7793},
support = {SEA-20-015//Southeastern Ontario Academic Medical Organization/ ; MM1181122/CAPMC/CIHR/Canada ; },
abstract = {Mitochondrial damage is a conserved feature of coronavirus infection, occurring with human (SARS-CoV-2, HCoV-OC43) and murine (MHV-1) coronaviruses. Coronaviruses damage mitochondria in airway epithelial cells (AEC), pulmonary artery smooth muscle cells (PASMC), pulmonary artery endothelial cells, immune cells and cardiomyocytes by causing rapid transcriptomic changes in nuclear-encoded genes regulating mitochondria and by viral proteins interacting with host mitochondrial proteins. Coronavirus infection causes mitochondrial depolarization, mitochondrial transition pore (MTP) opening, inhibition of the electron transport chain (ETC) and ATP synthetic apparatus, increased mitochondrial fission, apoptosis, and impaired mitochondrial oxygen sensing. Within hours of infection, SARS-CoV-2 induces transcriptional reprogramming of genes relevant to the mitochondrial matrix in AECs, downregulating mRNA encoding ETC complex I components and the ATP synthesis complex. These bioenergetic consequences of SARS-CoV-2 mitochondriopathy may contribute to long COVID. Infection also upregulates dynamin-related protein 1 (DRP1), activating mitochondrial fission while promoting apoptosis by activating apoptosis inducing factor (AIF) and caspase 7. Even without infection, transfection with specific coronaviral proteins opens the MTP and depolarizes the mitochondria, or activates DRP1 and AIF, promoting AEC damage or apoptosis, thereby contributing to diffuse alveolar damage. In human PASMCs, coronaviral M and Nsp9 proteins suppress hypoxic pulmonary vasoconstriction (HPV), a homeostatic mechanism in PASMCs that uses a mitochondrial oxygen sensor to redistribute blood flow to well-ventilated lung regions during pneumonia. Impairment of HPV, seen as intrapulmonary shunting, contributes to the profound hypoxaemia in COVID-19 pneumonia. Coronavirus-induced mitochondriopathy may have therapeutic relevance as blocking AIF-induced apoptosis or enhancing HPV appears beneficial in a MHV-1 model of COVID-19 pneumonia.},
}
@article {pmid41947189,
year = {2026},
author = {Zhou, L and Sun, Y and Yang, R and Zhao, Q and Xiao, M},
title = {Latent profile analysis of the symptoms for posttraumatic stress disorder and psychological resilience in Chinese adolescents experiencing post Covid-19: a quantetative study.},
journal = {BMC psychology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40359-026-03987-8},
pmid = {41947189},
issn = {2050-7283},
support = {2024CQ059//Humanities and Social Science Fund of Ministry of Education of China/ ; JY20240202//Chongqing Medical University/ ; CYYY-DSTDXM-202409//The First Affiliated Hospital of Chongqing Medical University/ ; },
}
@article {pmid41951239,
year = {2026},
author = {Casassus, B},
title = {Long covid's £8bn bill: OECD report warns pandemic continues to cast a "long shadow".},
journal = {BMJ (Clinical research ed.)},
volume = {393},
number = {},
pages = {s662},
doi = {10.1136/bmj.s662},
pmid = {41951239},
issn = {1756-1833},
}
@article {pmid41951431,
year = {2026},
author = {Tamariz, L and Rozenfeld, I and Iglesias, R and Bast, E and Avecillas, S and Shehadeh, L and Klimas, N and Palacio, A},
title = {Dysautonomia in Long COVID is Prevalent and Could Explain the Frequency of Symptoms.},
journal = {Clinical medicine &amp; research},
volume = {24},
number = {1},
pages = {28-34},
doi = {10.3121/cmr.2025.2054},
pmid = {41951431},
issn = {1554-6179},
mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/complications/epidemiology/physiopathology ; *Primary Dysautonomias/epidemiology/physiopathology/diagnosis ; Cross-Sectional Studies ; Prevalence ; Heart Rate ; Aged ; Adult ; SARS-CoV-2 ; Blood Pressure ; },
abstract = {Background: Long COVID presents with a variety of symptoms, some of which could be related to autonomic dysfunction. Our aim was to evaluate the prevalence of autonomic dysfunction in long COVID patients.Methods: We conducted a cross-sectional study and included all consecutive patients enrolled in several clinical research studies. We performed the following autonomic dysfunction markers: heart rate variability, heart rate, systolic and diastolic blood pressure changes during NASA Lean Test, cardiopulmonary exercise testing and a Composite-Autonomic-Symptom-Score (COMPASS)-31 scale. We used linear regression to calculate the contribution of each dysautonomia measure on symptom burden as measured by the modified COVID-19 Yorkshire scale.Results: We included 100 patients for this study. Our sample population had a mean age of 56+/-11 years, included 53% minorities, and 32% were women. Dysautonomia, as defined by an abnormal COMPASS-31, was seen in 82% (95% confidence interval [CI] 72-89) of our study population, while cardiovascular resting dysautonomia, as represented by an abnormal heart rate variability, was seen in 60% (95% CI 48-70) of our study population. Orthostatic hypotension was observed in 12% of our study population, and postural orthostatic tachycardia syndrome (POTS) was found in 10% of our study population. In our adjusted analysis, we found that the beta coefficient for the COMPASS-31 score (0.37) was significant on changes in a self-reported long COVID symptom burden. The orthostatic intolerance and gastrointestinal domains of the COMPASS-31 were associated with the highest long COVID symptom burden.Conclusion: Dysautonomia is common in long COVID patients and contributes to the overall symptoms seen in long COVID. Identifying dysautonomia has important diagnostic and therapeutic implications.},
}
@article {pmid41951954,
year = {2026},
author = {King, R and Ford, T and Coleman, Z and Hammond, E and Henley, D and Hirschtick, JL},
title = {Racial Disparities in Long COVID: Why Black Americans are Likely Underrepresented in Long COVID Estimates.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {41951954},
issn = {2196-8837},
}
@article {pmid41943185,
year = {2026},
author = {Maziero, MP and Lee, EA and Colpo, GD and Couture, L and Merrill, LC and Baskin, L and Cahuiche, AE and Petway, A and Fan, H and Reese, E and Anderson, KM and McCullough, LD and Schulz, PE and Ortiz, GJ},
title = {Cognitive Trajectories After Hospitalization for COVID-19: A 36-Month Longitudinal Study.},
journal = {The Journal of neuropsychiatry and clinical neurosciences},
volume = {},
number = {},
pages = {appineuropsych20250267},
doi = {10.1176/appi.neuropsych.20250267},
pmid = {41943185},
issn = {1545-7222},
abstract = {OBJECTIVE: Neurological symptoms are commonly reported among individuals with postacute sequelae of COVID-19 (PASC), with cognitive impairment being the most common feature, but cognitive trajectories in PASC have not been clearly defined. The authors determined long-term cognitive changes in a cohort of individuals hospitalized with COVID-19, characterized their distinct cognitive trajectories, and identified factors associated with each trajectory at 36 months posthospitalization.<br><br>METHODS: The sample comprised 630 patients who were hospitalized with severe COVID-19 symptoms; 214 patients returned for at least one follow-up assessment over a 36-month period. Cognitive function, including attention, cognitive flexibility, processing speed, and memory, was evaluated by using BrainCheck, a validated digital platform, at 3-6, 12, 24, and 36 months posthospitalization. Longitudinal changes in cognitive performance and their associations with demographic factors, medical history, and neuropsychiatric symptoms were analyzed with linear mixed-effects models.<br><br>RESULTS: Four distinct cognitive trajectories over 36 months were identified and characterized. Group 1 (N=103, 48%) exhibited consistent normal cognitive function, group 2 (N=14, 7%) transitioned from unimpaired to impaired, group 3 (N=29, 14%) changed from impaired to unimpaired, and group 4 (N=68, 32%) showed persistent impairment across all domains. Poorer cognitive outcomes were associated with Hispanic ethnicity, although effects varied across domains.<br><br>CONCLUSIONS: As with many viral encephalitides, some patients showed stable normal or abnormal cognition or improved cognition over time. Surprisingly, however, a fourth subset exhibited delayed cognitive decline. This observation suggests that PASC-associated mechanisms, perhaps including chronic cerebral inflammation, may cause progressive cognitive impairment well after the initial infection clears.},
}
@article {pmid41944489,
year = {2026},
author = {Jóźwiak, A and Lewandowska, A and Sawicka, D and Jędrzejewska, A and Braczko, A and Romanowska-Kocejko, M and Żarczyńska-Buchowiecka, M and Deptuła, M and Zawrzykraj, M and Pikuła, M and Kutryb-Zając, B and Hellmann, M and Mierzejewska, P},
title = {Post-COVID increase in N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) associates with inflammatory and endothelial activation markers.},
journal = {Nucleosides, nucleotides &amp; nucleic acids},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/15257770.2026.2650677},
pmid = {41944489},
issn = {1532-2335},
abstract = {COVID-19 is associated with long-term vascular complications, but the underlying mechanisms remain incompletely understood. During infection, NAD[+] homeostasis becomes dys-regulated, with excessive NAD[+] consumption and enhanced catabolic flux through nicotinamide methylation pathways. This imbalance leads to NAD[+] depletion accompanied by accumulation of pyridone metabolites, including N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY). These derivatives have been linked to oxidative stress, endothelial dysfunction, and cardiovascular risk, yet their role in long COVID remains unclear. We enrolled 26 post-COVID patients with persistent cardiovascular symptoms and 8 healthy controls. Serum concentrations of Met2PY and Met4PY were quantified by LC/MS. High-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNFα), interleukin-10 (IL-10), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured to assess systemic inflammation and endothelial activation. Statistical analyses included group comparisons and correlation analyses. We observed significantly elevated Met2PY levels (0.770 ± 0.08 vs. 0.389 ± 0.09 µmol/l) and a trend toward increased Met4PY (0.095 ± 0.01 vs. 0.055 ± 0.01 µmol/l) in post-COVID patients compared with controls. Both metabolites positively correlated with hsCRP. Importantly, Met2PY was associated with an unfavorable cytokine profile (higher TNFα/IL-10 ratio) and increased sICAM-1 levels, whereas no such associations were observed for Met4PY. Persistent dysregulation of NAD[+] metabolism and accumulation of pyridone metabolites, particularly Met2PY, are associated with markers of chronic endothelial activation and inflammation in long COVID. These findings support the potential utility of Met2PY as a biomarker to identify patients at higher risk for endothelial dysfunction and cardiovascular events, enabling more personalized risk stratification and follow-up.},
}
@article {pmid41946631,
year = {2026},
author = {Bartels, W and Kümpel, L and Ledebur, M and Jeitler, M and Heintze, C and Döpfmer, S},
title = {[Challenges and needs in the care for post-COVID patients in primary care practices in Berlin and Brandenburg - A qualitative study].},
journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.zefq.2026.02.004},
pmid = {41946631},
issn = {2212-0289},
abstract = {INTRODUCTION: General practitioners (GPs) play a central role as the first point of contact for patients with post-COVID. The aim of this qualitative study was to explore challenges and needs in the care for post-COVID patients from the perspective of GPs.<br><br>METHODS: Between October 2023 and May 2024, one face-to-face and two online focus groups were conducted with a total of 17 GPs from Berlin and Brandenburg. A self-developed guide was used, and data were analysed using framework analysis. In October 2024, results were validated in follow-up discussions with seven of these GPs.<br><br>RESULTS: Across all focus groups, GPs reported multiple challenges. These included diagnostic and therapeutic uncertainties, a lack of robust evidence, and gaps in service provision, such as long waiting times in specialised care facilities and feelings of helplessness in dealing with affected patients. Several care needs emerged from these challenges: low-threshold access to specialised outpatient clinics, the development of tailored rehabilitation concepts, and structured, up-to-date information for patients. In addition, GPs highlighted the need for stronger recognition and support of their role in post-COVID care.<br><br>DISCUSSION: GPs provide the lion's share of care for people affected by post-COVID, and thus their perspective should be given greater consideration in order to strengthen ambulatory care. The findings uncover genuine opportunities to address gaps in care and improve patient support.<br><br>CONCLUSION: GPs require support through structured care pathways and closer collaboration with specialised services. Further research is needed to develop cross-sectoral models of care that both improve patient outcomes and alleviate the burden on primary care.},
}
@article {pmid41947042,
year = {2026},
author = {Sahu, D and Van Nynatten, LR and Tweddell, D and Daley, M and Fraser, DD},
title = {Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.},
journal = {Clinical proteomics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12014-026-09601-8},
pmid = {41947042},
issn = {1542-6416},
}
@article {pmid41938337,
year = {2026},
author = {Saranya, K and Joseph, ER and Kalaiarasi, T and Karthiga, M},
title = {Generative AI in drug repurposing and biomarker discovery: a multimodal approach.},
journal = {Frontiers in bioinformatics},
volume = {6},
number = {},
pages = {1755412},
pmid = {41938337},
issn = {2673-7647},
abstract = {INTRODUCTION: Computational drug repurposing has been widely explored using similarity-based methods, network diffusion, matrix factorization, deep learning, and graph neural networks (GNNs). However, recent heterogeneous GNN models, such as TxGNN and GAT-based models, demonstrate serious limitations for real-world biomedical applications, including poor generalization to sparsely annotated diseases, limited disease-level adaptation, and inability to effectively combine heterogeneous evidence from curated databases, multi-omics profiles, and unstructured biomedical literature.<br><br>METHODS: This article proposes a heterogeneous attention-based meta-learning graph neural network named HAMGNN, which employs three major innovations: (i) relation-sensitive multi-head attention to prioritize biologically significant interactions among heterogeneous edge types, (ii) a disease-focused meta-learning framework enabling rapid adaptation to newly observed or under-informed diseases, and (iii) a literature-enhanced knowledge graph construction pipeline encoding high-confidence, LLM-extracted therapeutic information. The model was tested on a large multimodal biomedical knowledge graph assembled from DrugBank, DisGeNET, and Hetionet, comprising more than 2.2 million edges, using a stringent disjoint disease-based (cold-start) evaluation protocol.<br><br>RESULTS: HAMGNN achieved a receiver operating characteristic-area under the curve (ROC-AUC) of 0.98 and precision of 0.95, representing a 10%-15% improvement over TxGNN and GAT-GNN on unseen disease generalization. Translational applicability was demonstrated through Alzheimer's disease and Long COVID case studies, identifying clinically plausible repurposing candidates and disease-associated biomarker signatures via mechanistic pathways.<br><br>DISCUSSION: HAMGNN offers a generalized, biologically grounded, and unified framework for evidence-based drug repurposing and biomarker discovery in complex and emerging diseases.},
}
@article {pmid41938682,
year = {2026},
author = {Lam, KS and Suryadi, T and Su, DC and Suhaimi, A and Allam, AE and Yoon, Y},
title = {Novel Ultrasound-Guided Bilateral Simultaneous Hydrodissection of the Cervical Sympathetic Chain and Vagus Nerves: A Detailed Technical Description With Anatomical Correlation.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106250},
pmid = {41938682},
issn = {2168-8184},
abstract = {The vagus nerve and cervical sympathetic chain regulate autonomic function and are implicated in chronic pain and post-viral autonomic syndromes. Hydrodissection with 5% dextrose is established for peripheral nerves, but simultaneous ultrasound-guided hydrodissection of both cervical autonomic nerves has not been described. We describe a reproducible ultrasound-guided technique for bilateral simultaneous hydrodissection of the cervical sympathetic chain and vagus nerves using 5% dextrose without local anesthetic. The procedure uses a high-frequency linear transducer at C6-C7 and an in-plane lateral 25-gauge needle approach, performing the deeper sympathetic chain hydrodissection first (prevertebral fascia superficial to the longus colli), followed by vagus nerve hydrodissection within the carotid sheath. Injection is performed slowly (12-18 minutes per side) to permit full delivery and patient comfort. We report procedural outcomes in 10 patients (30 sessions) treated for post-COVID-related autonomic dysfunction. All procedures were completed successfully. Total injectate was 60 mL of 5% dextrose per side (approximately 30 mL for the sympathetic chain and 30 mL for the vagus nerve). The deep-to-superficial sequence preserved sonographic visualization and avoided air-bubble artifact. No procedural complications occurred (including bradycardia, hypotension, voice changes, dysphagia, hematoma, or infection). At a minimum 12-month follow-up, patients maintained clinical improvement without additional interventions. Ultrasound-guided bilateral simultaneous hydrodissection of the cervical sympathetic chain and vagus nerves with 5% dextrose is technically feasible and well tolerated. A deep-to-superficial injection sequence and very slow administration optimize visualization and delivery. Detailed clinical outcomes are presented separately.},
}
@article {pmid41939132,
year = {2026},
author = {Wunderle, M and Ribeiro, A and Lethen, I and Wicklein, R and Feneberg, E and Wöhnl, A and Negele, J and Kesseler, V and Niedermayer, S and Lech, M and Wallraven, T and Schmaderer, C},
title = {Serum NfL and GFAP in post-COVID syndrome: minimal evidence of CNS injury after adjusting for confounders.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1750121},
pmid = {41939132},
issn = {1662-5102},
abstract = {BACKGROUND: Post-COVID syndrome (PCS) often includes neurological symptoms, but evidence for persistent CNS injury remains inconsistent. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astroglial injury. We investigated whether serum NfL and GFAP differ between PCS patients and recovered controls after adjusting for age and renal function.<br><br>METHODS: In this prospective single-center case-control study, serum NfL and GFAP were quantified using Simoa&#xae; (Quanterix) in 102 PCS patients and 102 recovered controls. Group comparisons employed Mann-Whitney tests and ANCOVA-style multivariable linear regression of log-transformed biomarkers adjusted for age, sex, and eGFR. Associations with eGFR were examined in multivariable models, and findings were validated in an age- and sex-matched cohort.<br><br>RESULTS: Age emerged as the primary determinant of NfL and GFAP concentrations. The inverse correlations with renal function (NfL &#x3c1;&#x202f;=&#x202f;-0.23; GFAP &#x3c1;&#x202f;=&#x202f;-0.33) and the initially higher GFAP in PCS (60.4 vs. 52.3&#x202f;pg/mL; p&#x202f;=&#x202f;0.002) were largely explained by age. After adjustment for age, sex, and eGFR, neither biomarker showed independent differences between groups (adjusted GMRs: NfL 1.04 [0.91-1.18], p&#x202f;=&#x202f;0.59; GFAP 1.10 [0.96-1.26], p&#x202f;=&#x202f;0.15). In an age- and sex-matched cohort (71 pairs), adjusted analyses confirmed no difference in NfL (p&#x202f;=&#x202f;0.48), while GFAP demonstrated a significant increase in PCS (&#x3b2;&#x202f;=&#x202f;0.15, p&#x202f;=&#x202f;0.025).<br><br>CONCLUSION: GFAP concentrations were modestly elevated in PCS in an age- and sex-matched cohort and persisted after adjustment for kidney function, whereas NfL showed no group differences. These findings argue against widespread neuroaxonal injury in PCS and suggest only a subtle astroglial signal in a subset of patients. Rigorous adjustment for confounders-particularly age, sex, and renal function-is essential for valid interpretation of serum neuroinjury biomarkers in PCS.},
}
@article {pmid41939224,
year = {2026},
author = {Silva, AI and Byrne, KC and Pollak, L and Gundry, K and Manousakis, GE and Metzler, AI and Lenglet, C and Eberly, LE and Kendall-Thomas, J and Kantarci, OH and Zeydan, B and Mukerji, SS and Yasar, S and Ashizawa, T and Kantarci, K and Ratai, EM and Öz, G and , },
title = {Factors associated with severe neurological sequelae of COVID-19: findings from the multicenter COVID-BRAIN imaging cohort.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1754342},
pmid = {41939224},
issn = {1662-5161},
abstract = {INTRODUCTION: Neurological post-acute sequelae of COVID-19 (neuroPASC) are associated with persistent cognitive dysfunction and quality-of-life decline. We aimed to identify clinical, behavioral and sociodemographic factors associated with neuroPASC symptom burden two years after COVID-19 among individuals without prior neurological disease.<br><br>METHODS: In this prospective, observational study, individuals with neuroPASC (n&#x202f;=&#x202f;102) and controls without symptomatic COVID-19 (n&#x202f;=&#x202f;74), all without prior neurological, psychiatric, or post-viral conditions, were enrolled between February 2022 and June 2024 across five academic sites. An unsupervised algorithm identified clusters with differing self-reported neurological symptom burden within the neuroPASC group. Functional differences between clusters were evaluated using quality-of-life, neurological and cognitive evaluations. Demographics, behavioral history, comorbidities, and blood biomarkers were compared across clusters and controls. Multivariable logistic regression assessed predictors of neuroPASC severity, including demographics, body-mass-index, Charlson Comorbidity Index, Framingham Risk Score, pre-existing endocrine/metabolic and/or gastrointestinal/hepatobiliary conditions, COVID-19 vaccination prior to infection, hospitalization during acute infection, and cumulative alcohol use.<br><br>RESULTS: Two clusters emerged based on neurological symptom burden, labeled "high-burden" and "low-burden" neuroPASC, reflecting differences in the number and frequency of symptoms. Both clusters had deficits in quality-of-life and cognitive function compared to controls, with greater impairment in high-burden than low-burden neuroPASC. The clusters did not differ by sex, education, tobacco and cannabis use, blood pressure, body-mass-index, HbA1C, days since infection, hospitalization during COVID-19, pre-COVID vaccination rate, antibody-positivity, inflammation, and neurodegeneration biomarkers. The high-burden cluster was older and exhibited higher comorbidity burden and greater cumulative alcohol use compared with the low-burden cluster and controls. Pre-existing endocrine/metabolic and gastrointestinal/hepatobiliary conditions were more common in high-burden (63%) than in low-burden neuroPASC (35%). After adjusting for clinical and demographic factors, these pre-existing conditions remained the only independent predictor of severity, conferring a 3.5-fold increase in the odds of high-burden versus low-burden neuroPASC.<br><br>DISCUSSION: Older age, higher comorbidity burden, greater cumulative alcohol use, and endocrine/metabolic and gastrointestinal conditions, rather than acute COVID-19 severity, were observed in the high-burden neuroPASC cluster. After multivariable adjustment, only pre-existing endocrine/metabolic and/or gastrointestinal/hepatobiliary conditions remained independently associated with high-burden neuroPASC, conferring a 3.5-fold increase in odds and highlighting the need for targeted post-infection monitoring in at-risk patients.},
}
@article {pmid41939860,
year = {2026},
author = {Limongelli, A and Bozzano, F and Hajabbas Farshchi, A and Bellucci, M and Bavastro, M and Castellano, C and Pesce, G and Antonini, F and Incensi, A and Giannoccaro, MP and Uccelli, A and Del Zotto, G and Moretta, L and Donadio, V and Benedetti, L and De Maria, A},
title = {Immune correlates underlying small fiber neuropathy presenting as vaccine-associated post-acute SARS- coronavirus syndrome.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1752120},
pmid = {41939860},
issn = {1664-3224},
mesh = {Humans ; Male ; Female ; *Small Fiber Neuropathy/immunology/etiology/diagnosis ; Middle Aged ; *COVID-19/immunology/prevention &amp; control ; *SARS-CoV-2/immunology ; Adult ; *COVID-19 Vaccines/adverse effects/immunology ; Aged ; Angiotensin-Converting Enzyme 2/immunology ; Post-Acute COVID-19 Syndrome ; Neuropilin-1/immunology ; Vaccination/adverse effects ; },
abstract = {BACKGROUND: A spectrum of adverse events overlapping with Post-acute Sequelae of SARS-CoV-2 infection (PASC) occurs in some patients following SARS-CoV-2 vaccination including small fiber neuropathy (SFN) and cognitive symptoms.<br><br>AIMS: Accruing information regarding disease course and immune response imbalances in these patients.<br><br>METHODS: We studied 71 previously healthy patients with neurological symptoms following SARS-CoV-vaccination. All had negative neurological workup for central/peripheral involvement (MR, EMG/EN). Cutaneous biopsy (21pts.) and peripheral blood sampling (20pts) were performed for anti-idiotype Ab analysis (ACE-2,NRP-1) (ELISA, IF) and for Flowcytometric analysis.<br><br>RESULTS: Paresthesia, cognitive impairment and autonomic symptoms agreed with SFN international definition. Comparative differences included abrupt onset, presence of simultaneous diverse paresthesia across multiple body regions frequently affecting the facial and cervical regions (44%) and the trunk (26%), associated to dysautonomia. Median time from vaccination to symptom manifestation was 3 days (mean &#xb1; SD: 8.76 &#xb1; 17.4 days). Symptom severity was still high (5.9 &#xb1; 1.9 mean+SD) at the time of evaluation and sampling, (382 &#xb1; 133 days from onset. Reduced small fiber density was observed in 19/21 biopsies. Anti-ACE-2 antibodies in 9/71pts. (12%) and 4/19 (21%) vaccinated HD sera and NRP-1 reactivity in 14/71 (20%) patient and 1/19 (5%) HD sera were not significantly increased. Peripheral NKG2D+CD8+ and NKG2D+DNAM-1+CD4+ T-cells were increased. Circulating inflammatory CD34+ cells were increased and generated in vitro a prevalence of NKG2D+DNAM-1+ T-cells.<br><br>CONCLUSION: PASC-vac SFN is associated with persistent immune imbalances common to other immune-mediated diseases. Additional effort to identify immune mechanisms unleashing PASC-vac SFN will contribute to modulate future early interventions for these patients and refine vaccine design.},
}
@article {pmid41940032,
year = {2026},
author = {Cazzola, M and Rogliani, P and Calzetta, L and van Haren, FMP and Page, C and Matera, MG},
title = {Redox signaling in chronic airway diseases: pathogenic mechanisms and therapeutic implications.},
journal = {Frontiers in physiology},
volume = {17},
number = {},
pages = {1734890},
pmid = {41940032},
issn = {1664-042X},
abstract = {Chronic airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis, impose a significant global health burden. A central unifying feature of these diseases is redox imbalance, which is characterized by an excess of reactive oxygen and nitrogen species (ROS/RNS) that overwhelms the body's antioxidant defenses, causing cellular dysfunction, inflammation, and tissue damage. Physiological ROS/RNS are essential for immune regulation and transcriptional control, but chronic oxidative stress disrupts these processes, driving disease progression. In asthma, eosinophil- and epithelial-derived ROS worsen airway hyperresponsiveness, induce mucus overproduction, and reduce steroid effects. COPD involves neutrophil-dominated inflammation, mitochondrial dysfunction, protease- and oxidant-mediated extracellular matrix degradation, and accelerated senescence. Bronchiectasis features persistent neutrophilic oxidative injury, microbial colonization, impaired mucociliary clearance, and progressive airway destruction. Exogenous oxidants, cigarette smoke, biomass fuels, pollutants, and pathogens further burden antioxidant systems, including superoxide dismutases, catalase, glutathione peroxidase, and Nrf2-regulated pathways. Redox dysregulation also contributes to post-COVID sequelae, promoting ongoing airway inflammation, fibrosis, and systemic complications. Therapeutic strategies targeting redox imbalance, mainly thiol-based antioxidants, Nrf2 activators, NADPH oxidase inhibitors, and mitochondria-targeted antioxidants, show mechanistic promise but face challenges in specificity, bioavailability, and clinical translation. Advancing precision redox medicine requires biomarker-guided patient stratification, high-resolution redox proteomics, single-cell and organoid models, and spatial imaging to identify disease-specific redox endotypes. Modulating pathological oxidative stress while preserving physiological signaling offers a novel avenue to improve outcomes. Understanding redox biology in airway disease highlights the potential of precision antioxidant strategies as adjuncts to conventional therapies, representing a paradigm shift in managing chronic airway disorders.},
}
@article {pmid41941235,
year = {2026},
author = {Alhasawi, MAI and Farwa, U and Muteeb, G and Aatif, M and El Oirdi, M and Raza, MA and Farhan, M},
title = {Neuropsychiatric Sequelae of COVID-19: A Systematic Review of Acute and Prolonged Effects.},
journal = {CNS &amp; neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273424823260119063256},
pmid = {41941235},
issn = {1996-3181},
abstract = {INTRODUCTION: Following the global emergence of SARS-CoV-2, it has become evident that COVID-19 can produce persistent, multisystemic symptoms known as "long COVID." Neurocognitive and neuropsychiatric symptoms are reported in approximately 40% of patients, often resulting in significant difficulties with daily functioning, workplace challenges, increased healthcare consumption, and a substantial economic burden. This condition is further linked to serious neurological complications, such as encephalitis, stroke, seizures, and Guillain-Barré syndrome.<br><br>METHODS: This study comprised a comprehensive literature review to identify and understand existing research on the long-term neurological impacts of COVID-19. The process involved evaluating investigations into multisystemic symptoms and reviewing documented clinical cases of neurological complications by searching relevant databases for studies published between January 2020 and December 2024.<br><br>RESULTS: The work identified that while the neurological burden of long COVID-19 is high, there are currently very few treatments described in the literature. Furthermore, the treatments that do exist are often inadequately defined, leaving a gap in standardized clinical protocols for managing neurocognitive decline post-infection.<br><br>DISCUSSION: The persistence of these symptoms suggests a need for a deeper understanding of the underlying mechanisms of post-viral neurological damage. The discussion centres on the intersection of cognitive impairment and economic impact, emphasizing that the lack of defined therapeutic pathways hinders recovery and increases the long-term societal burden of the pandemic.<br><br>CONCLUSION: This review summarizes current evidence on the neurological and neuropsychiatric sequelae of long COVID-19. It highlights the urgent need for emerging therapeutic approaches and structured management strategies to alleviate cognitive and neuropsychiatric impairments in this patient population effectively.},
}
@article {pmid41941341,
year = {2026},
author = {Kulkarni, C and Haase, E and Esparza, E and Blancke, A and Sathyamoorthy, M},
title = {Retrospective Analysis of Clinical Repurposing of Dipyridamole and L-Arginine for Treatment of Long COVID Endothelitis.},
journal = {Current cardiology reviews},
volume = {},
number = {},
pages = {},
doi = {10.2174/011573403X435762251202114307},
pmid = {41941341},
issn = {1875-6557},
abstract = {INTRODUCTION: The effect of treatment with L-arginine and dipyridamole for the reduction of symptoms of fatigue, difficulty performing activities of daily living (ADLs), dyspnea, and mental health decline in patients with Long COVID endothelitis was studied in this research, leading to conclusions that are presented.<br><br>METHODS: Forty-four patients with documented Long COVID endothelitis were enrolled in this retrospective, IRB-approved analysis evaluating clinician-directed treatment strategies initiated during the COVID-19 pandemic. Patients received either dipyridamole alone, L-arginine alone, or combination therapy. Clinical responses were assessed at 6 weeks and 6 months postinitiation, and a subset of nine patients also completed a structured, patient-reported outcomes survey approximately two years after starting treatment.<br><br>RESULTS: Of the 44 subjects identified, clinical follow-up at 6 weeks demonstrated a significant overall symptom improvement (p=0.0115). At 6 months, symptom improvement remained substantial but lost statistical significance (p=0.09). Combination therapy (dipyridamole and Larginine) showed sustained improvement at both 6 weeks (68.8%) and 6 months (62.5%). Dipyridamole alone demonstrated high early response (80%) but markedly reduced efficacy at 6 months (20%). Statistical comparisons between combination therapy and monotherapy groups did not yield significant results, likely due to limited sample sizes. Patient-reported outcomes supported clinical findings, with combination therapy yielding the lowest symptom burden in fatigue, dyspnea, and depression, and the highest functional capacity.<br><br>DISCUSSION: This study addressed a critical unmet need in Long COVID management, a condition affecting middle-aged and older adults with substantial symptom burden, including fatigue (reported in up to 45% of patients), dyspnea, and cognitive dysfunction. The therapeutic benefit observed with dipyridamole and L-arginine likely stems from their complementary mechanisms: dipyridamole's antiplatelet and anti-inflammatory effects may reduce microvascular dysfunction and microthrombosis, while L-arginine enhances nitric oxide production, supporting endothelial function and vascular homeostasis. Both agents possess favorable safety profiles, making them reasonable options in the absence of validated alternatives for Long COVID endothelitis.<br><br>CONCLUSION: Treatment with dipyridamole and L-arginine, particularly in combination, was associated with meaningful improvements in fatigue, dyspnea, ability to perform ADLs, and mental health symptoms in patients with Long COVID. These preliminary findings underscore the potential benefit of these therapeutic agents, though larger, randomized controlled studies are necessary to confirm efficacy and enhance statistical power.},
}
@article {pmid41934421,
year = {2026},
author = {Shakeel, A and Sircar, K and Popli, DB},
title = {Xerostomia after COVID-19 recovery: A preliminary investigation.},
journal = {The Indian journal of medical research},
volume = {163},
number = {1},
pages = {122-125},
doi = {10.25259/IJMR_1570_2025},
pmid = {41934421},
issn = {0971-5916},
mesh = {Humans ; *Xerostomia/epidemiology/virology/etiology/physiopathology ; *COVID-19/complications/epidemiology/virology/physiopathology ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Aged ; Surveys and Questionnaires ; },
abstract = {Background and objectives Xerostomia, or dry mouth, was frequently reported during COVID-19 infection, but its persistence after recovery remains underexplored. This study aimed to assess the prevalence and duration of xerostomia following recovery from COVID-19 infection. Methods This observational study included 50 participants who had recovered from COVID-19. They were surveyed using a xerostomia assessment questionnaire and underwent the modified Schirmer test (MST) to measure their salivary flow rate. Results Overall, n=31(62%) of participants reported one or more xerostomia-related symptoms after recovery. "Feeling of dry mouth" (n=22, 44%) was the most common, followed by nocturnal water intake (n=18, 36%), difficulty swallowing dry food (n=7, 14%), and reliance on liquids during swallowing (n=6, 12%). Hyposalivation (MST <15 mm at 3 min) was observed in 10% (n=5) of participants, all of whom were infected during the second wave (Delta variant). A significant association was noted between self-reported dry mouth and MST findings (P=0.029). Symptoms persisted up to 15 months post-recovery. Interpretation and conclusions Xerostomia may persist after COVID-19 recovery, with potential implications for oral health. Early recognition and management are warranted.},
}
@article {pmid41936816,
year = {2026},
author = {Reeder, HT and Kleinman, LC and Stockwell, MS and Thaweethai, T and Pant, DB and Rhee, KE and Jernigan, TL and Snowden, JN and Salisbury, AL and Kinser, PA and Milner, JD and Tantisira, KG and Warburton, D and Mohandas, S and Wood, JC and Fitzgerald, ML and Carmilani, M and Krishnamoorthy, A and Foulkes, AS and Gross, RS and , },
title = {School Difficulties and Long COVID in Children and Adolescents.},
journal = {Academic pediatrics},
volume = {},
number = {},
pages = {103314},
doi = {10.1016/j.acap.2026.103314},
pmid = {41936816},
issn = {1876-2867},
abstract = {OBJECTIVE: Pediatric Long COVID (LC) is an infection-associated chronic condition following SARS-CoV-2 infection. While research has begun to elucidate clinical phenotypes, functional impacts are not well described.<br><br>METHODS: Cross-sectional data from the NIH-funded Researching COVID to Enhance Recovery (RECOVER) pediatric observational cohort was analyzed to assess associations in school-age children (6 to 11 years) and adolescents (12 to 17 years) between LC and caregiver-reported school-related functional outcomes. LC was defined using RECOVER age group-specific symptom-based LC research indices. The primary outcome was worsening of child grades. Secondary outcomes included difficulty paying attention, limited fun with friends, and having an Individualized Education Program (IEP). Using age-stratified analyses, children with and without LC were matched based on age, sex, and dates of infection and enrollment, to estimate risk ratios (RRs) between LC and each outcome.<br><br>RESULTS: The cohort included 1,976 children (406 school-age, 1,570 adolescent). 18% of school-age children and 29% of adolescents with LC had reported worsened grades, compared to 7% and 11% without LC, respectively [school-age: adjusted RR 2.18 (95% CI: 1.15-4.11); adolescent: adjusted RR 2.39 (95% CI: 1.86-3.06)]. In both age groups, children with LC were more likely to have difficulty paying attention, limited fun with friends, and IEPs.<br><br>CONCLUSIONS: LC in school-age children and adolescents was negatively associated with functional school-related outcomes, including academic performance, attention, and peer interactions. As LC affects a substantial proportion of U.S. children, these findings highlight the urgent need to develop, provide, and evaluate school-related services for children and adolescents with LC.},
}
@article {pmid41933948,
year = {2026},
author = {Nygren-Bonnier, M and Holland, AE},
title = {Physiotherapy management of long COVID in adults.},
journal = {Journal of physiotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jphys.2026.03.001},
pmid = {41933948},
issn = {1836-9561},
}
@article {pmid41928318,
year = {2026},
author = {Atkins, T and Glasziou, P and Chakraborty, S and Turner, T and Rada, G and Byambasuren, O},
title = {Living evidence syntheses for long COVID therapeutics: combining rigorous protocols to build efficiency while maintaining rigour.},
journal = {Systematic reviews},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13643-026-03178-x},
pmid = {41928318},
issn = {2046-4053},
support = {2035160//Australian Government 2023 Medical Research Future fund PASC grant/ ; 2034238//Australian Government 2023 Medical Research Future fund PASC grant/ ; 2032847//Australian Government 2023 Medical Research Future fund PASC grant/ ; },
abstract = {BACKGROUND: Given the rapidly changing evidence, the creation and maintenance of a living systematic review database of therapeutics for long COVID is an ideal and necessary approach considering the rapidly changing evidence that continues to be identified. This paper describes methods and results of a collaboration between three teams who produced a living literature review on long COVID therapeutics-Australian Living Evidence Collaboration (ALEC), Bond University, and Epistemonikos COVID-19 L.OVE (Living Overview of Evidence) database.<br><br>METHODS: We took a collaborative and iterative approach to analyse the commonalities and differences between each project and develop an agreed comprehensive, collective approach. A plan for ongoing (monthly) updates and dissemination was built.<br><br>RESULTS: Despite minor differences, there was also a clear alignment of goals between the three teams. Differences in search strategy, search methods and screening criteria were identified, investigated, and resolved. A comparison of overlaps helped establish a common collaborative approach. A combined library of 218 randomised controlled trials and 56 systematic reviews was created which led to the optimised search strategy. The combined 218 RCT library covered 20 different treatment categories of which 14 were pharmacological and 6 were non-pharmacological. Further refinements and collaborations led to a transformed initial database library of 102 randomised controlled trials as of June 2024 before the team commenced monthly updates.<br><br>CONCLUSIONS: Despite initial differences, a comprehensive search strategy based on the collaboration of the three teams was developed. Ongoing monthly updates were initiated and are now planned for well into the future to make continual and rapid updates to the library of evidence surrounding therapeutics for long COVID. Where global public health is concerned, it is valuable to review and refine processes in the early stages, so that they can be reliable. We recommend open collaboration to achieve the goal of creating accessible, efficient, and reliable evidence syntheses.},
}
@article {pmid41930109,
year = {2026},
author = {Friedberg, F and LeBaron, TW},
title = {Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1760210},
pmid = {41930109},
issn = {2296-858X},
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction, yet it currently lacks FDA-approved treatments. Molecular hydrogen (H2), administered primarily as hydrogen-rich water (HRW), has emerged as a potential therapeutic candidate due to its selective antioxidant effects, anti-inflammatory activity, and support of mitochondrial and cellular homeostasis. These mechanisms align with several biological abnormalities implicated in ME/CFS, including oxidative stress, chronic inflammation, and impaired energy metabolism. This narrative mini-review summarizes mechanistic evidence relevant to ME/CFS and evaluates three developmental clinical studies of HRW in this population. Although early trials are small and methodologically limited, moderate-dose HRW consumed over extended durations has demonstrated feasibility and preliminary benefits in reducing fatigue and improving physical function, with generally mild side effects. Overlapping findings in Long COVID further suggest potential applicability across related post-viral fatigue conditions. Key limitations include small sample sizes, reliance on self-report outcomes, and the absence of objective biomarkers. Future research should prioritize larger, rigorously controlled trials incorporating remote biometric and biochemical assessments to clarify mechanisms of action and identify responsive subgroups. Overall, molecular hydrogen represents a promising, low-burden adjunctive therapy warranting further investigation in ME/CFS.},
}
@article {pmid41932118,
year = {2026},
author = {Juszczyk, M and Nawaz, S and Mahdi, A and Lewinter, C and Ricci, F and Ståhlberg, M and Fedorowski, A},
title = {Post-COVID Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia: Prevalence, Overlap, and Clinical Characteristics.},
journal = {JACC. Advances},
volume = {5},
number = {5},
pages = {102702},
doi = {10.1016/j.jacadv.2026.102702},
pmid = {41932118},
issn = {2772-963X},
}
@article {pmid41932346,
year = {2026},
author = {Soares, L and Romatowski, CH and Assaf, G and de Canson, C},
title = {The case for routine patient review in long COVID research.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(26)00134-9},
pmid = {41932346},
issn = {1474-4457},
}
@article {pmid41932347,
year = {2026},
author = {Camici, M and Piano Mortari, E and Del Duca, G and Cimini, E and Mazzotta, V and De Ponte, C and Mastrorosa, I and Mazzotta, S and Pinnetti, C and Notari, S and Bordoni, V and Gili, S and Prencipe, G and Maggi, F and Carsetti, R and Girardi, E and Antinori, A and Agrati, C},
title = {Intravenous immunoglobulin treatment for long COVID: a case report of clinical and immunological findings.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(26)00063-0},
pmid = {41932347},
issn = {1474-4457},
abstract = {A previously healthy 39-year-old man developed highly symptomatic post-COVID-19 condition (also known as long COVID) marked by cognitive dysfunction, disabling fatigue, and autonomic symptoms unresponsive to multiple multidisciplinary interventions. Given the presence of markedly elevated serum autoantibodies against G protein-coupled receptors, high-dose intravenous immunoglobulin therapy was initiated at 400 mg/kg per day for 5 consecutive days. After 4 weeks, a maintenance dose of 500 mg/kg was administered for 1 day, followed by two further maintenance cycles consisting of 500 mg/kg per day for 3 consecutive days, each given at 4-week intervals. In parallel, the patient underwent a cognitive stimulation intervention. Neurological symptoms were assessed with the Fatigue Assessment Scale and the WHO Disability Assessment Schedule 2.0, and the immunological profile was longitudinally analysed during intravenous immunoglobulin treatment. Fatigue scores normalised, neurocognitive performance returned to normal value, and quality of life improved after the first infusion and fully recovered within 1 year. Immunological profiling revealed the presence of an inverted CD4 to CD8 T-cell ratio that persisted during the whole follow-up. We also identified a CD8[+] T cell-monocyte complex and spontaneous IFNγ release. Intravenous immunoglobulin therapy was associated with a significant reduction of these complexes, spontaneous IFNγ and TNF production, markers of endothelial inflammation, and circulating autoantibody titres. This patient provides exploratory evidence that high-dose intravenous immunoglobulin was associated with sustained clinical recovery from long COVID over 1 year of follow-up, accompanied by immunological changes consistent with modulation of post-viral immune dysregulation, including a reduction in pathogenic T cell-monocyte synapses. Although causal inference cannot be established from a single patient, these findings suggest that this cellular interaction can contribute to long COVID and that immunomodulation could represent a rational therapeutic approach to be evaluated in selected patients.},
}
@article {pmid41933012,
year = {2026},
author = {Haack, M and Chan, J and Engert, LC and Dang, R and Wang, H and Borducchi, EN and Shah, K and Liu, J and Sun, H and Ganglberger, W and Karlson, EW and Prather, AA and Barouch, DH and Mullington, JM},
title = {The effect of pre-existing sleep disturbance on T cell responses to SARS-CoV-2 variants, pro-inflammatory and pro-resolving mediators, and glucocorticoid sensitivity in Long COVID.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-47039-y},
pmid = {41933012},
issn = {2045-2322},
}
@article {pmid41933051,
year = {2026},
author = {Moreels, S and Smith, P and Charafeddine, R and Castanares-Zapatero, D and van Cauteren, D and Speybroeck, N},
title = {Identifying Long Covid phenotypes and their association with personal characteristics, healthcare use, and daily life burden: population-based study in Belgium.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-47228-9},
pmid = {41933051},
issn = {2045-2322},
abstract = {Long Covid (LC), a multisystem disorder with persistent symptoms > 4 weeks post COVID-19, has impacted healthcare systems substantially. As information is scarce for Belgium, this study aimed to identify LC phenotypes and assess participant characteristics, healthcare use and daily life burden by phenotype. The last survey wave of COVimpact (a longitudinal online cohort study among Belgian adults recruited after SARS-CoV-2 infection) focused on LC with questions on healthcare utilization and perceived daily impact. A latent class analysis (LCA) identified phenotypes, based on symptom type, disease duration, and LC-related disability. Backward multivariable multinomial logistic regression explored predictors of LC class membership. Among 1,840 respondents self-reporting LC, four phenotypes emerged. Class 1 presented mild clinical outcomes, class 2 and 3 presented moderate clinical outcomes, differentiated by symptoms of memory problems and brain fog (class 2), and respiratory problems and muscle/joint pain (class 3), and class 4 included the most severe clinical outcomes. Compared to class 1, being older, female, lower educated, non-European, obese and experiencing moderate to severe acute COVID-19 symptoms predicted higher class severity. Diagnosis, healthcare use and support differed among adults with moderate and severe LC, many reported insufficient healthcare access and major disruption to daily life, including absenteeism from work/school. People with severe LC were the most financially impacted. By distinguishing LC phenotypes, this study enhances understanding of varying healthcare trajectories and daily life impacts. Healthcare planning and support should be more effectively tailored to the specific needs of those affected by LC.},
}
@article {pmid41933338,
year = {2026},
author = {Ostojic, SM},
title = {Beyond plasma signatures: reframing bioenergetic disruption in long COVID as a neurological disorder.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41933338},
issn = {1479-5876},
}
@article {pmid41924624,
year = {2026},
author = {Hasan, H and Hohmann, D and Hysko, K and Ibahrine, S and Skeries, V and Dold, K and Pöhler, GH and Wetzke, M and Hansmann, G},
title = {Cardiovascular phenotyping of children and adolescents with post-COVID syndrome (PCS) at initial diagnosis - a prospective observational single-center study.},
journal = {Frontiers in cardiovascular medicine},
volume = {13},
number = {},
pages = {1665734},
pmid = {41924624},
issn = {2297-055X},
abstract = {BACKGROUND: Post-COVID Syndrome (PCS) is an emerging, highly relevant topic in public health as it negatively affects quality of life and educational/work performance at all ages. To date, there is hardly any robust data on cardiac function in PCS (Long-COVID) available, particularly not in children and adolescents. The aim of this study was to conduct deep cardiovascular phenotyping in pediatric patients with PCS at initial presentation using cardiac MRI and echocardiography, including strain/tissue tracking analysis.<br><br>METHODS: Prospective, single center cohort study at Hannover Medical School, Germany (10207_BO_K_2022). PCS was defined as follows: persistent symptoms such as reduced physical performance, poor concentration, mood symptoms, headaches, sleep disorders and dysosmia, for at least 12 weeks after PCR-confirmed SARS-CoV-2 infection. A total of 100 pediatric patients (age 7-18 years, 56 female) and 20 age/gender matched healthy controls (age 8-18 years, 12 female) were enrolled between 03/2022 and 11/2023. Data collection consisted of 12-lead electrocardiogram (ECG), protocol-driven echocardiography (Echo; Philips EPIQ 7 ultrasound system, Philips Medical Systems), including tissue Doppler Echo and biventricular strain analysis (TOMTEC, Philips). 42 of the 100 PCS patients (age 9-18 years, 26 female) and 28 age/gender matched healthy controls (age 8-18 years, 14 female) received comprehensive cardiac magnetic resonance imaging (CMR; 3.0 T MRI system Magnetom Vida, Siemens Healthineers), including cine mass/volumes quantification in short axis (SAX) and tissue tracking (strain) analysis of the RV and LV (cvi 42). Laboratory studies included serum NTproBNP and Troponin c. Data are presented as mean&#x2009;&#xb1;&#x2009;SEM.<br><br>RESULTS: CMR-derived RV global radial strain (RVGRS) (22.6&#x2009;&#xb1;&#x2009;1.00% vs. 27.1&#x2009;&#xb1;&#x2009;1.13%; p&#x2009;=&#x2009;0.003), and RV global circumferential strain (RVGCS) (-13.5&#x2009;&#xb1;&#x2009;0.55 vs. -15.2&#x2009;&#xb1;&#x2009;0.51%; p&#x2009;=&#x2009;0.045) were significantly decreased in PCS vs. CON. Children with PCS also tended to have mildly reduced RVEF (50.9&#x2009;&#xb1;&#x2009;0.80 vs. 53.5&#x2009;&#xb1;&#x2009;0.66%; p&#x2009;=&#x2009;0.259). RV mass index was increased in PCS compared to CON (19.06&#x2009;&#xb1;&#x2009;0.47 vs. 16.4&#x2009;&#xb1;&#x2009;0.53&#x2005;g/m[2]; p&#x2009;=&#x2009;0.0002), though in normal range referred to age-appropriate normal values. In contrast, CMR-derived LV variables (LVEF, LVEDV, LVESV, LV mass), including tissue tracking (strain) analysis (LVGLS, LVGCS, LVGRS), revealed similar values in PCS and control subjects. ECG and Echo data analysis did not show significant differences in PCS vs. CON.<br><br>CONCLUSION: PCS is associated with decreased CMR-based radial and circumferential RV contractility (RVGRS, RVGCS) and slightly increased RV mass in children with PCS compared to healthy, age/gender matched controls. In contrast, LV contractility (strain) and mass were not affected. CMR feature tracking (strain) appears to be more sensitive than echocardiographic strain analysis. Whether the aforementioned RV alterations are causal for the reported cardiopulmonary exercise limitations in pediatric PCS is unknown, and should be investigated further.},
}
@article {pmid41924648,
year = {2026},
author = {Al-Qerem, W and Baaj, R and Jarab, A and Al Bawab, AQ and Hasan Agha, MI and Eberhardt, J and Al-Sa'di, L and Obidat, R and Abu Hour, S},
title = {Validation of the Arabic Version Post-COVID-19 Symptom Scale (PCSS-Ar) for Assessing Long COVID-19 Severity Among Arabic-Speaking Populations: A Factor Analysis and Rasch Analysis Study.},
journal = {Risk management and healthcare policy},
volume = {19},
number = {},
pages = {572130},
pmid = {41924648},
issn = {1179-1594},
abstract = {PURPOSE: The COVID-19 pandemic has led to long COVID-19, a condition characterized by persistent, multisystemic symptoms. This study validated the Arabic version of the Post-COVID-19 Symptom Scale (PCSS-Ar) to assess long COVID-19 severity in Jordan.<br><br>PATIENTS AND METHODS: A cross-sectional online survey was conducted with 582 Jordanian adults (aged &#x2265;18 years), recruited via social media. The PCSS-Ar underwent content validity evaluation by an expert panel, followed by confirmatory factor analysis (CFA) and Rasch analysis to assess its psychometric properties.<br><br>RESULTS: The final 24-item, five-factor model demonstrated an excellent fit (CFI = 0.95, TLI = 0.95, SRMR = 0.02) and strong internal consistency (Cronbach's &#x3b1; &#x2265; 0.97). Rasch analysis confirmed the tool's ability to differentiate symptom severity levels effectively. Key findings indicated that higher frequencies of COVID-19 infection were significantly associated with more severe long COVID-19 symptoms, whereas mild initial infections were linked to lower symptom severity. Notably, lower income was associated with higher PCSS-Ar scores, suggesting socioeconomic disparities in post-COVID-19 recovery. Female participants had lower PCSS-Ar scores, contrasting with previous studies, indicating a potential population-specific effect.<br><br>CONCLUSION: The PCSS-Ar is a validated and reliable tool for assessing long COVID-19 symptoms in Arabic-speaking populations. Its application in both clinical and research settings can help monitor symptom progression and guide targeted interventions.},
}
@article {pmid41926033,
year = {2026},
author = {Gierthmuehlen, M and Schmieder, K and Thon, N and Gierthmuehlen, PC},
title = {Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID: Results of the Randomized, Placebo-Controlled Clinical Pilot Trial COVIVA.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41926033},
issn = {2193-8253},
abstract = {INTRODUCTION: Fatigue is the most prevalent symptom in "long COVID", affecting 6-7% of patients after COVID-19 infection. Its pathophysiology remains unclear, with viral persistence, immune dysregulation, and mitochondrial dysfunction among proposed mechanisms. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulatory approach, has been suggested as a potential treatment.<br><br>METHODS: We conducted a randomized, sham-controlled, single-blinded pilot study to evaluate adherence and clinical effects of taVNS in long COVID-related fatigue. Forty-five patients were randomized 1:1:1 to sham stimulation, sub-threshold taVNS, or above-threshold taVNS for 4&#xa0;weeks using the Conformit&#xe9; Europ&#xe9;enne (CE)-certified tVNS-L device (25 Hz, 250 &#xb5;s, 4 h/day). The primary co-endpoints were fatigue severity (MFI-20) and adherence, defined as mean daily stimulation duration. Secondary endpoints included depressive symptoms (BDI-II), health-related quality of life (SF-36), and post-COVID symptom burden (PCS).<br><br>RESULTS: Of 45 enrolled patients (mean age 42.4 years; 73% female), 4 (8.9%) dropped out early. Mean stimulation time was 236 min/day, fulfilling the adherence criterion in&#x2009;>&#x2009;80% of participants. Adverse events were mild, including skin irritation (6.7%) and vertigo (6.7%). Across all groups, questionnaire scores improved over time; however, no statistically significant differences were observed between the sham and active stimulation groups. Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data.<br><br>CONCLUSION: taVNS was safe, feasible, and associated with high adherence in long COVID-related fatigue, but showed no superiority over sham stimulation. Larger multicenter trials with more homogeneous populations and objective biomarkers are required to determine whether taVNS confers therapeutic benefit in this condition.<br><br>TRIAL REGISTRATION: The trial was approved by the ethics committee (23/7798) and registered at the German Clinical Trials Register, identifier DRKS00031974.},
}
@article {pmid41926871,
year = {2026},
author = {Palacio, AM},
title = {Owning the moment: A call for humanism in medicine to address complex chronic illness.},
journal = {Patient education and counseling},
volume = {149},
number = {},
pages = {109609},
doi = {10.1016/j.pec.2026.109609},
pmid = {41926871},
issn = {1873-5134},
}
@article {pmid41918009,
year = {2026},
author = {Raine, G and Khouja, C},
title = {Exploring duplication in reviews of Long COVID: 2020-2023.},
journal = {Systematic reviews},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13643-026-03174-1},
pmid = {41918009},
issn = {2046-4053},
abstract = {BACKGROUND: The unnecessary duplication of reviews is a recognised problem in the field of evidence synthesis. This paper reports findings from a study exploring potential duplication of effort in reviews on the frequency and/or risk of Long COVID that were published during the first 3 years of the COVID-19 pandemic.<br><br>METHODS: We extracted and summarised the aims and key characteristics of 112 reviews identified from 5 published evidence summaries commissioned by the National Institute for Health and Care Research (NIHR) for the Department of Health and Social Care (DHSC), England, which covered the period from January 2020 to January 2023.<br><br>RESULTS: There was significant similarity in the aims and characteristics of the 112 reviews. We identified 43 reviews reporting on any persistent symptoms/effects and 69 that focused on specific symptoms/effects; overlap in the conditions studied was common. The majority of reviews focused on individuals of any age (n&#x2009;=&#x2009;62); where restrictions were applied (n&#x2009;=&#x2009;50), all but six reviews focused on adults. Most reviews focused on both hospitalised and non-hospitalised patients (n&#x2009;=&#x2009;97), and authors searched the same time periods. Half of authors reported publishing a protocol prospectively (n&#x2009;=&#x2009;58), and only a minority received specific review funding (n&#x2009;=&#x2009;39).<br><br>CONCLUSIONS: Our findings raise concerns about unnecessary duplication of effort and the extent to which all reviews we assessed will have added substantially to the Long COVID evidence base. Researchers should seek to minimise research redundancy and only conduct new reviews when a genuine knowledge gap exists.},
}
@article {pmid41918727,
year = {2026},
author = {Stallmach, A and Layer, P and Katzer, K and Reuken, PA},
title = {Lessons from irritable bowel syndrome: potential for understanding and managing post-COVID.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1717324},
pmid = {41918727},
issn = {1664-3224},
mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis/etiology ; *COVID-19/complications ; *SARS-CoV-2 ; },
abstract = {Post-COVID presents a complex medical challenge characterized by persistent symptoms following SARS-CoV-2 infection. Similarities between post-COVID and post-infectious Irritable Bowel Syndrome (PI-IBS) suggest that the latter can serve as a useful model for understanding pathophysiological mechanisms and developing therapeutic approaches. Both conditions are functional disorders triggered by an acute infection, with multifactorial etiology and limited biomarker-based diagnostics. The variability of symptoms and the high frequency of comorbidities make these disorders particularly difficult to diagnose. Diagnostic efforts may be further hindered by the stigmatization of such disorders among healthcare providers, the health insurance industry, and the general public. This article explores the parallels between PI-IBS and post-COVID, highlighting, on the one hand, what can be learned from the management of IBS to better address the needs of patients with post-COVID long-term sequelae, and, on the other hand, raising doubts-based on decades of research into drug therapy development for IBS-about the likelihood of a rapidly available treatment for post-COVID.},
}
@article {pmid41919824,
year = {2026},
author = {Modesto, MMO and Oliveira, NN and Pereira, ND and Baccon, WC and Carreira, L and Salci, MA},
title = {Influence of alcohol on the worsening of COVID-19 and the occurrence of long COVID.},
journal = {Revista latino-americana de enfermagem},
volume = {34},
number = {},
pages = {e4813},
doi = {10.1590/1518-8345.7679.4813},
pmid = {41919824},
issn = {1518-8345},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Cross-Sectional Studies ; Female ; Middle Aged ; Retrospective Studies ; *Alcohol Drinking/epidemiology/adverse effects ; Adult ; Aged ; Young Adult ; Hospitalization/statistics &amp; numerical data ; Brazil/epidemiology ; Adolescent ; },
abstract = {OBJECTIVE: to analyze the alcohol consumption patterns of adults and older adults before the development of COVID-19 and the influence of alcohol consumption on the outcomes and complications of long COVID.<br><br>METHOD: cross-sectional study based on data from a retrospective cohort conducted with adults and older adult who had COVID-19 and who consumed alcohol before infection with the disease. A standardized electronic form was used to collect sample data and a path model was adjusted to prove the theoretical model on the influence of alcohol consumption on negative outcomes for COVID-19.<br><br>RESULTS: sample of 1,171 participants who responded to the question about alcohol. Of these, 408 (34.84%) reported alcohol consumption prior to the disease. The majority were male, younger, highly educated, and had children over the age of 18. The presence of chronic noncommunicable diseases leads to an 11% increase in the chance of hospitalization and a 12% increase in the chance of long COVID. The age of the participants affected alcohol use and directly affected the need for hospitalization.<br><br>CONCLUSION: It is important to adopt intervention strategies aimed at reducing alcohol consumption, especially in contexts of syndemic, to mitigate the associated risks.},
}
@article {pmid41920383,
year = {2026},
author = {Buchholz, I and Lüdtke, L and Härter, M and Janssen, MFB},
title = {Psychometric validation of a cognition and social participation bolt-on for the EQ-5D-5L in SARS-CoV-2 infected German healthcare workers.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {5},
pages = {},
pmid = {41920383},
issn = {1573-2649},
}
@article {pmid41921919,
year = {2026},
author = {Welfordsson, P and Brodén, M and Niemi, M and Diwan, V and Shah, K and Pattanadara, V and Hallgren, M},
title = {Feasibility and preliminary effects of a yoga program developed for adults with post COVID-19 condition (Breathe Easy): pilot randomized controlled trial.},
journal = {Complementary therapies in medicine},
volume = {},
number = {},
pages = {103367},
doi = {10.1016/j.ctim.2026.103367},
pmid = {41921919},
issn = {1873-6963},
abstract = {INTRODUCTION: Effective medical management of post COVID-19 condition (post COVID) remains challenging. Symptoms are heterogenous, debilitating, and impact health-related quality of life (HR-QoL). Complementary treatments are needed that can be self-managed and improve health. Yoga is a promising strategy that may help reduce post-COVID symptoms but remains understudied.<br><br>METHODS: We co-designed a unique yoga intervention for adults with post COVID and evaluated its feasibility and preliminary effects. Two-group parallel, pilot randomized controlled trial with blinded follow-up. Participants were randomized (1:1) to the 12-week yoga program or a health promotion (HP) intervention. All participants received usual medical treatment for post COVID. Twenty-nine participants aged 30-65 years were recruited and randomized (86% follow-up). The primary outcome was feasibility and the secondary outcome was HR-QoL (SF-36). Data were analysed as intention-to-treat using linear mixed modelling. The trial was prospectively registered and approved by the Swedish Ethical Review Authority (2023/06518-01).<br><br>RESULTS: Through a consensus development process involving yoga experts in India and Sweden, post COVID researchers, and patient advocates, we successfully co-designed and pilot tested a yoga program developed for adults with post COVID. The intervention was feasible with high adherence (&#x2265;2 sessions/week = 65%; &#x2265;1 session/week = 95%) and no serious adverse events reported. Preliminary (underpowered) analyses showed no pre-to-post intervention group differences (SF-36 physical health: B = -1.30, 95% CI = -3.60, 1.00, p =.269; mental health: B = 3.49, 95% CI = -0.06, 7.04, p =.054).<br><br>CONCLUSION: Participation in a yoga program developed for patients with post COVID was feasible. Adequately powered trials are needed to assess whether yoga may help to improve symptoms associated with the condition.},
}
@article {pmid41922885,
year = {2026},
author = {van der Bie, J and Bakker, J and Verschoor, EJ and Nutma, E and Middeldorp, J and Beaino, W and Kassiou, M and Danon, JJ and Langermans, JAM and Windhorst, AD and Stammes, MA},
title = {Comparison of [[18]F]DPA-814 with [[18]F]DPA-714 for TSPO Imaging in an Experimental Model.},
journal = {Molecular imaging and biology},
volume = {},
number = {},
pages = {},
pmid = {41922885},
issn = {1860-2002},
abstract = {PURPOSE: [[18]F]DPA-714 is a valuable tracer for studying (neuro)inflammation, with well-characterized tracer kinetics and an established imaging window. However, its clinical utility is restricted by the TSPO polymorphism (rs6971), which influences binding affinity in humans. The newly developed tracer [[18]F]DPA-814 overcomes this limitation and has shown promising results in a preclinical rat model. To further assess its clinical potential, we compared [[18]F]DPA-814 to [[18]F]DPA-714 for inflammation imaging in SARS-CoV-2-infected macaques in a longitudinal setting.<br><br>PROCEDURES: Dynamic positron emission tomography (PET) imaging was conducted in four healthy macaques to identify the optimal imaging window for [[18]F]DPA-814. Four additional macaques were infected with SARS-CoV-2 and monitored for 12 months using whole-body PET-computed tomography (CT) with both tracers. Baseline scans were compared to PET-CTs obtained at 4, 9 and 16 days and at 6 and 12 months post-infection, covering the head, thorax and abdomen. Tracer uptake was assessed in several organs.<br><br>RESULTS: At baseline, [[18]F]DPA-814 showed higher lung uptake with minimal washout compared to [[18]F]DPA-714. Although lung lesions developed after infection, [[18]F]DPA-814 did not demonstrate lesion-specific uptake, unlike [[18]F]DPA-714. In the brain, the tracers also displayed divergent uptake patterns despite comparable TSPO levels across animals and regions.<br><br>CONCLUSIONS: [[18]F]DPA-814 exhibits a distinct whole-body distribution, particularly in the lungs and brain, in both na&#xef;ve and SARS-CoV-2-infected macaques compared with [[18]F]DPA-714, likely reflecting differences in tracer kinetics. Based on these data, [[18]F]DPA-814 may not fully replace [[18]F]DPA-714 for lung and brain imaging, and further studies are required to evaluate its suitability in other anatomical regions.},
}
@article {pmid41913858,
year = {2026},
author = {Shahid, MM and Neequaye, NN and Shifera, AS},
title = {Multiple Evanescent White Dot Syndrome (MEWDS) Following COVID-19 Infection: A Presumed Recurrence.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104405},
pmid = {41913858},
issn = {2168-8184},
abstract = {Multiple evanescent white dot syndrome (MEWDS) is a transient self-limiting likely post-viral inflammatory condition involving the outer retina and inner choroid and has been reported following several vaccinations and viral infections, including COVID-19. Photopsias are a common presenting symptom but rarely persist after the acute phase of MEWDS. We present a case of an otherwise healthy 29-year-old woman who developed persistent photopsias of the right eye following COVID-19 infection. These photopsias persisted for several months and worsened after a second COVID-19 infection, which is atypical of MEWDS. Fundus autofluorescence (FAF) demonstrated several characteristic punctate hyperautofluorescent spots. Her symptoms and fundus lesions resolved after a few weeks of diagnosis without treatment. COVID-19 has several reported ocular manifestations, including MEWDS. While most cases of MEWDS following COVID-19 infection are singular instances, our case was a presumed recurrence. MEWDS is often self-limiting, but in this case, symptoms persisted for several months, suggesting the possibility of long COVID, which is a poorly understood phenomenon.},
}
@article {pmid41914122,
year = {2026},
author = {Singhal, A and Patle, A and Patil, S and Lakkireddy, M and Raja, S and Pyati, A and Arora, A and Dhole, S and Varathrajan, S and Patil, P and Sahoo, D and Taranikanti, M and John, NA and Ravi, N},
title = {Covid-19 and Its Arthritic Footprint: Clinical, Laboratory and Imaging Insights from a Cross Sectional Study in a Tertiary Center in Telangana.},
journal = {Mymensingh medical journal : MMJ},
volume = {35},
number = {2},
pages = {641-648},
pmid = {41914122},
issn = {2408-8757},
mesh = {Humans ; Female ; *COVID-19/complications ; Cross-Sectional Studies ; Middle Aged ; Male ; Prospective Studies ; Adult ; Tertiary Care Centers ; *Arthritis/etiology/diagnostic imaging/diagnosis/virology ; Aged ; SARS-CoV-2 ; Arthralgia/etiology ; },
abstract = {The post-Covid-19 syndrome, also referred to as "Long Covid", can present with arthritic symptoms. A cross-sectional, prospective study was done on post Covid-19 patients at a tertiary centre in Telangana. This study included a total of 139 RT-PCR-confirmed Covid-19 patients, who were diagnosed with arthritis in the time interval between 1 to 6 months post Covid recovery. Demographic data, clinical data, blood investigations, inflammatory markers and imaging investigations were recorded. Majority of the patients (65.5%; n=91) were women and the mean age of the participants was 50.8 years. 77.0% (n=107) had arthralgia, 44.6% (n=62) had joint swelling, 25.2% (n=35) had myalgia and 5.8% (n=8) had fatigue. The most common joint affected was the knee (92.0%; n=128), followed by wrist (10.25%; n=4) and ankle (n=1). Abnormal Hb levels (43.9%; n=61), RBC counts (9.4%; n=13), WBC counts (13.7%; n=19) and ESR (26.6%; n=37), D-dimer (50.4%; n=70), LDH levels (49.6%; n=69), uric acid (36.0%; n=50), ferritin (35.5%; n=49) and rheumatoid factor (10.8%; n=15), were recorded in participants. Joint arthritic changes on radiographs and ultrasoundwere recorded in 77.0% had 95.7% of the participants respectively. Covid arthritis is one of the common features of Long Covid patients. Many patients suffer from joint aches and swelling which cause sufficient impairment causing majority of the individuals.},
}
@article {pmid41914490,
year = {2026},
author = {Koberssy, Z and Daher, J and Durieux, JC and Atieh, O and Baissary, J and Abboud, M and Ailstock, K and Cummings, M and Funderburg, N and McComsey, GA},
title = {Comparison of Immune Activation and Gut Barrier Dysfunction between Long COVID and HIV infection.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag146},
pmid = {41914490},
issn = {1537-6613},
abstract = {BACKGROUND: Human Immunodeficiency Virus (HIV) infection is characterized by persistent immune dysregulation and inflammation, with emerging evidence suggesting overlapping pathophysiological mechanisms with Long COVID. Biomarkers of systemic inflammation and gut integrity may provide insight into shared and distinct pathways underlying these conditions. The status of the anti-inflammatory vitamin K may play a role in sustained inflammation in these conditions.<br><br>METHODS: This cross-sectional study enrolled participants belonging to one of 3 groups: individuals with Long COVID (Long COVID; n=108) without HIV, participants with HIV (PWH), virologically suppressed with no previous COVID-19 infection (HIV+; n=256), and controls without Long COVID or HIV (controls; n=193). Plasma samples were analyzed for inflammatory, gut integrity biomarkers, and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) as an established marker of vitamin K status. Associations were assessed using multivariable linear and logistic regression models adjusted for demographic, metabolic, and lifestyle covariates.<br><br>RESULTS: 557 participants were included. Long COVID was independently associated with elevated oxLDL (&#x3b2;=0.39 vs. HIV, &#x3b2;=0.54 vs. controls; P<0.001 for both). PWH had higher odds of worse vitamin K status [OR: 1.5; 95% CIs (1.02-2.2), P=0.04]. Independent of Long COVID or HIV status, worse vitamin K status was strongly associated with higher levels of inflammatory markers.<br><br>CONCLUSION: Long COVID and HIV share chronic immune dysregulation features but demonstrate distinct inflammatory profiles. Those findings highlight the importance of large longitudinal studies to delineate shared versus unique inflammatory pathways to guide potential Long COVID therapeutic strategies.},
}
@article {pmid41914537,
year = {2026},
author = {Nezamdoust, B},
title = {Rethinking Risk: Intersectional Inequalities in Long COVID in the United States.},
journal = {Sociology of health &amp; illness},
volume = {48},
number = {4},
pages = {e70174},
doi = {10.1111/1467-9566.70174},
pmid = {41914537},
issn = {1467-9566},
mesh = {Humans ; United States/epidemiology ; *COVID-19/epidemiology/ethnology/complications ; Female ; Male ; *Health Status Disparities ; Adult ; Middle Aged ; Socioeconomic Factors ; *Social Class ; SARS-CoV-2 ; Sex Factors ; Black or African American/statistics &amp; numerical data ; White People/statistics &amp; numerical data ; Aged ; *Health Inequities ; Risk Factors ; Prevalence ; White ; },
abstract = {Post-acute sequelae of coronavirus disease 2019 (PASC), also known as Long COVID, is a chronic, multisystem condition affecting millions of U.S. adults, with profound social, medical and economic consequences. Despite its widespread impact, disparities in who is most affected remain poorly understood, especially through an intersectional sociological lens. Using a sociological and intersectional framework, this study analyses a national sample (N = 535,300) from the Household Pulse Survey to explain disparities in Long COVID risk across race, gender and socioeconomic status. The analysis demonstrates that socioeconomic advantage does not equally protect all groups; specifically, higher-SES Black women show significantly elevated Long COVID prevalence compared to White counterparts, challenging claims of racial parity in Long COVID rates. Moreover, although women generally show higher Long COVID risk, intersectional analysis uncovers that the gender gap narrows among high-SES White women, suggesting that social privilege can mitigate health risks. These findings emphasise that structural inequalities, rather than biology, may primarily drive Long COVID inequities and highlight the importance of intersectional sociological analyses for understanding health disparities. The results call for equity-focused interventions addressing the unequal social burden of Long COVID and advancing sociological theory on the social determinants of health.},
}
@article {pmid41914684,
year = {2026},
author = {Brüssow, H},
title = {Antivirals Targeting Coronavirus RNA-Dependent RNA Polymerase and Main Protease: From Mechanisms of Action to Outcomes in COVID-19 Clinical Trials.},
journal = {Microbial biotechnology},
volume = {19},
number = {4},
pages = {e70342},
doi = {10.1111/1751-7915.70342},
pmid = {41914684},
issn = {1751-7915},
mesh = {Humans ; *Antiviral Agents/therapeutic use/pharmacology ; *COVID-19 Drug Treatment ; *SARS-CoV-2/drug effects/enzymology ; Clinical Trials as Topic ; COVID-19/virology ; Hydroxylamines/therapeutic use/pharmacology ; *Coronavirus RNA-Dependent RNA Polymerase/antagonists &amp; inhibitors ; Cytidine/analogs &amp; derivatives/therapeutic use ; Alanine/analogs &amp; derivatives/therapeutic use ; Animals ; Adenosine Monophosphate/analogs &amp; derivatives/therapeutic use ; Coronavirus 3C Proteases/antagonists &amp; inhibitors ; },
abstract = {The rapid global spread of SARS-CoV-2 triggered an unprecedented effort to develop effective antivirals. Among the first approved agents was remdesivir, an injectable nucleoside analogue developed by Gilead Sciences, that led to chain termination of viral RNA synthesis and showed broad antiviral activity against RNA viruses. Early clinical results were mixed: The US ACTT-1 trial reported an accelerated recovery and reduced mortality in treated patients, while the WHO Solidarity and a European trial revealed no impact of remdesivir on mortality. In contrast, a US trial in outpatients demonstrated a clear clinical benefit when treatment was administered early. Molnupiravir, an orally applicable nucleoside analogue developed by Merck, induces lethal mutations in the viral genome rather than chain termination. Molnupiravir showed in vivo antiviral activity against coronaviruses in different animals. In MOVe-OUT trials, molnupiravir reduced the rate of hospitalisation in treated outpatients. In the PANORAMIC trial, molnupiravir reduced the time to recovery in outpatients but not their rate of hospitalisation. No drug effect of molnupiravir was seen in the RECOVERY trial with hospitalised COVID-19 patients. Using structural biology and medicinal chemistry approaches, Pfizer developed nirmatrelvir, an oral inhibitor of the major coronavirus protease. In high-risk but not in standard-risk COVID-19 patients, the combination nirmatrelvir/ritonavir reduced the rate of hospitalisation (EPIC HR and SR trials). Retrospective cohort studies showed treatment effects in defined patient groups. This review compares the efficacy and clinical performance of different antivirals, including emerging drugs such as obeldesivir and alternative protease inhibitors (lopinavir, simnotrelvir). It further examines their roles in prophylaxis, treatment of long covid symptoms, pharmacological considerations and antiviral resistance. Particular attention is given to factors underlying variable outcome of the trials, including viral variant evolution, population immunity increases, disease severity changes and timing of therapy initiation.},
}
@article {pmid41915390,
year = {2026},
author = {Wee, LE and Abdul Malek, MIB and Tan, YY and Lim, JT and Tan, WC and Ngiam, JN and Lee, M and Vong, EKY and Chiew, CJ and Li, RJ and Tan, IBH and Lye, DC and Tan, KB},
title = {Postacute Sequelae Following Omicron COVID-19 in Patients With Cancer.},
journal = {JAMA network open},
volume = {9},
number = {3},
pages = {e264037},
doi = {10.1001/jamanetworkopen.2026.4037},
pmid = {41915390},
issn = {2574-3805},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Neoplasms/complications/epidemiology ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; SARS-CoV-2 ; Singapore/epidemiology ; Adult ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; },
abstract = {IMPORTANCE: Information on the burden of postacute sequelae of SARS-CoV-2 infection (or long COVID) in patients with cancer during endemicity is limited.<br><br>OBJECTIVE: To evaluate the risk of postacute diagnoses and/or symptoms compatible with long COVID in a population-based cohort of patients with cancer and high rates of vaccination and/or boosting who were infected during Omicron predominance compared with those with negative test results (hereinafter, noninfected patients). Results were additionally stratified by COVID-19 severity and receipt of therapeutics.<br><br>This retrospective, population-based cohort study used health care claims databases to construct cohorts of adult patients with cancer in Singapore who were infected with SARS-CoV-2 during Omicron predominance (January 1 through December 31, 2022), and contemporaneous noninfected patients. Patients were followed up to 300 days from the index date and data were analyzed from February 1, 2022, through October 27, 2023.<br><br>EXPOSURE: SARS-CoV-2 infection.<br><br>MAIN OUTCOMES AND MEASURES: Competing risks regression (death as a competing risk), with overlap weights applied, was used to estimate risks of new-incident diagnoses and/or symptoms compatible with long COVID following SARS-CoV-2 infection in patients with cancer compared with noninfected patients. Risks of postacute sequelae following COVID-19 hospitalization in patients with cancer were further contrasted against influenza hospitalizations (January 1, 2017, to December 31, 2022).<br><br>RESULTS: A total of 76&#x202f;807 patients with cancer were included in the analysis (48 279 [62.9%] female); 39&#x202f;256 had SARS-CoV-2 infection and 37&#x202f;551 were noninfected patients. The mean (SD) age was 63.9 (13.7) years. The mean (SD) follow-up time was 263.1 (36.2) days for patients infected with SARS-CoV-2 and 264.8 (32.5) days for noninfected patients. Most patients had solid-organ cancer (72&#x202f;497 of 76 807 [94.4%]) and were boosted (71 550 of 76 807 [93.2%]); only a minority with SARS-CoV-2 infection (3571 of 39 256 [9.1%]) required acute hospitalization. No significant difference in risk of postacute diagnoses compatible with long COVID was observed in patients with SARS-CoV-2 infection (hazard ratio [HR],&#x2009;0.98; 95% CI,&#x2009;0.92-1.04) compared with noninfected patients. While risk of postacute symptoms following COVID-19 was modestly increased (HR,&#x2009;1.09; 95% CI,&#x2009;1.01-1.19; P&#x2009;=&#x2009;.048), statistical significance was not attained after adjustment for multiple comparisons. However, significantly increased risk of postacute sequelae was observed among patients hospitalized for COVID-19 compared with noninfected patients (HR for any diagnosis,&#x2009;1.36 [95% CI,&#x2009;1.18-1.56]; HR for any symptom,&#x2009;1.48 [95% CI,&#x2009;1.22-1.76]; P&#x2009;<&#x2009;.001 for both); risks remained elevated even among hospitalized cases receiving COVID-19 therapeutics. Risks of postacute sequelae following COVID-19 hospitalization in patients with cancer did not significantly differ from those associated with seasonal influenza hospitalizations.<br><br>CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that among highly boosted patients with cancer, the overall risk of postacute sequelae following Omicron SARS-CoV-2 infection was not significantly elevated compared with noninfected patients; however, patients who were hospitalized for COVID-19 remained at increased risk of postacute sequelae despite administration of COVID-19 therapeutics. These findings further suggest that COVID-19 vaccination and boosting remain important in mitigating the risk of long COVID among immunocompromised patients during endemicity.},
}
@article {pmid41917225,
year = {2026},
author = {Bonuck, K and Gao, Q and Congdon, S and Kim, RS},
title = {Long COVID disability burden in US adults.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {41917225},
issn = {2730-664X},
abstract = {BACKGROUND: Five years since the scientific and patient communities first identified the syndrome now known as Long COVID, affected individuals lack treatments, and the US lacks population-based data on its disability burden and correlation with National Institutes of Health (NIH) funding. Moreover, akin to other debilitating conditions it often co-occurs with, e.g., Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia, Long COVID disproportionately impacts females whose concerns are often marginalized.<br><br>METHODS: We quantify Long COVID years lived with disability (YLDs= prevalence x disability weight) in US adults and its actual/YLD-commensurate average annual NIH FY2022-2024 funding versus 68 comparator conditions, by sex predominance. We derive Long COVID prevalence from Census Bureau surveys (9/2022-8/2023) and apply disability weights from the Global Burden of Disease Study.<br><br>RESULTS: Long COVID YLDs approximate those of Alzheimer's and Asthma. Long COVID received 14% of its disability commensurate funding: $106 million vs. $739.8 million. ME/CFS is the most under-funded condition, receiving <1% of its YLD proportionate funding. Among conditions analyzed, 24 are female-predominant (we estimate Long COVID funding two ways), 12 male-predominant, and 33 show no sex predominance. Among the 12 below-median funded/above-median YLD conditions, 7/12 are female-predominant, none are male-predominant. Median funding/per YLD is 5.2 times higher for male- vs. female-predominant conditions (7.0 vs 1.3 million per YLD, p&#x2009;=&#x2009;0.007). Overall, YLDs explain 6.5% of funding variance in a linear regression model using YLD as the sole predictor (Adjusted R-squared: 0.065).<br><br>CONCLUSIONS: With chronic conditions like Long COVID rising, disability burden merits greater consideration in funding decisions, as does biological sex.},
}
@article {pmid41907807,
year = {2026},
author = {Kaleem, S and Sawano, M and Arun, AS and Warner, F and Zhou, T and Huang, C and Bhattacharjee, B and Lu, Y and Iwasaki, A and Nwanyanwu, K and Ahmed, IIK and Krumholz, HM},
title = {Ocular Symptoms in Long COVID: A Cross-Sectional Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {565596},
pmid = {41907807},
issn = {1177-5467},
abstract = {INTRODUCTION: This study compared demographics, socioeconomic characteristics, pre-pandemic health conditions, newly diagnosed health conditions, and long COVID symptoms between participants with and without self-reported new-onset ocular symptoms after COVID-19 infection.<br><br>MATERIAL AND METHODS: We performed a cross-sectional analysis of the Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) study. Adults who self-reported long COVID, completed surveys between May 2022 and October 2023, and did not report post-vaccination syndrome were included. Ocular symptoms were defined as self-reported new-onset blurring or loss of vision, dry eyes, or floaters/flashes of light attributed to long COVID. Group comparisons used percentages for categorical variables and median and interquartile range (IQR) for continuous variables as well as Bonferroni-adjusted P-values. A gradient-boosted tree model was used to identify symptoms that differentiated groups.<br><br>RESULTS: Among 595 participants (median age 46 years [IQR 38-56]; 73% female), 341 (57%) reported ocular symptoms. Pre-pandemic comorbidities were similar between groups. Participants with ocular symptoms had lower EuroQoL visual analogue scale health scores (median 40 [IQR 30-59] vs 51 [IQR 39-70], P < 0.001), greater financial difficulties (20% vs 8.8%, P < 0.001), increased worry about housing stability (16% vs 5.4%, P < 0.001), and higher rates of new-onset dysautonomia (38% vs 15%, P < 0.001) and myalgic encephalomyelitis/chronic fatigue syndrome (21% vs 9.1%, P = 0.005). Key differentiating symptoms included dizziness, cold intolerance, pressure at the base of the head, tinnitus, and tremors.<br><br>CONCLUSION: Individuals with long COVID with self-reported new-onset ocular symptoms after infection may represent a more severe phenotype, with poorer health status and greater socioeconomic challenges despite similar pre-pandemic health profiles.},
}
@article {pmid41908724,
year = {2026},
author = {Zavala-Arciniega, L and Lisabeth, L and Slocum, EM and Orellana, RC and Fleischer, NL},
title = {Sex differences in the prospective associations of long COVID with incident cardiometabolic and respiratory diseases from a population-based longitudinal study in Michigan.},
journal = {Preventive medicine reports},
volume = {65},
number = {},
pages = {103449},
pmid = {41908724},
issn = {2211-3355},
abstract = {AIM: To evaluate longitudinal associations of Long COVID with incident cardiometabolic and respiratory outcomes among adults.<br><br>METHODS: We used the Michigan COVID-19 Recovery Surveillance Study, a population-based longitudinal study of adults with PCR-confirmed COVID-19 in Michigan. We included adults with COVID-19 who responded to the baseline (data collection: 06/2020-12/2022) and follow-up survey (data collection: 01/2022-11/2023) and were free of each outcome at baseline. Long COVID was defined as recovery taking &#x2265;90&#xa0;days after infection or no recovery. We evaluated four self-reported incident outcomes: 1) diabetes, 2) hypertension, 3) heart disease, and 4) asthma. We conducted modified Poisson models to examine longitudinal exposures-outcomes association separately, overall and stratified by sex.<br><br>RESULTS: Long COVID was associated with higher past-year incidence of heart disease and asthma in multivariable models, when we stratified the models by sex, we observed statistically significant associations for females only between Long COVID and all measured outcomes, except hypertension (Females&#xa0;=&#xa0;diabetes: Incidence Risk Ratio (IRR)&#xa0;=&#xa0;2.33 95% CI 1.15,4.73; heart disease: IRR&#xa0;=&#xa0;1.98 95% CI 1.10,3.57; asthma: IRR&#xa0;=&#xa0;2.99 95% CI 1.60,5.57).<br><br>CONCLUSION: Study findings reinforce the importance of preventing Long COVID and to monitor sequelae including incident disease outcomes for those who are experiencing Long COVID.},
}
@article {pmid41909842,
year = {2026},
author = {Yang, Y and Li, B and Yang, J},
title = {Editorial: Therapeutic targets and strategies for long COVID and post-viral syndrome.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1820002},
doi = {10.3389/fcimb.2026.1820002},
pmid = {41909842},
issn = {2235-2988},
}
@article {pmid41911553,
year = {2026},
author = {Reis, G and Dos Santos Moreira Silva, EA and Medeiros Silva, DC and Thabane, L and Ferreira, TS and Reis, LLF and Figueiredo Guimaraes Almeida, AP and Menezes Amaral, M and Savassi, LCM and de Souza Campos, VH and Campos Simplicio, MI and Barra Ribeiro, L and de Souza Medeiros, T and Campos Siqueira, T and Vieira, TS and Drumond Rausse, N and Garofolo, TC and Fagundes Silva, EC and Harari, O and D'Urso, G and Forrest, JI and Park, J and Nachega, JB and Lindsell, C and Glenn, JS and Thorlund, K and Dybul, M and Mills, EJ and , },
title = {The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID : An Adaptive Randomized Trial.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-03959},
pmid = {41911553},
issn = {1539-3704},
abstract = {BACKGROUND: Postacute sequelae of SARS-CoV-2, or long COVID, presents a major therapeutic challenge, with fatigue being a prevalent and debilitating symptom.<br><br>OBJECTIVE: To assess the efficacy of fluvoxamine and metformin for long COVID fatigue.<br><br>DESIGN: Randomized, placebo-controlled, adaptive trial. (ClinicalTrials.gov: NCT06128967).<br><br>SETTING: Outpatient sites in Brazil.<br><br>PARTICIPANTS: 399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection.<br><br>INTERVENTION: Participants were randomly assigned to fluvoxamine (100 mg twice daily), metformin (750 mg twice daily), or matching placebo for 60 days.<br><br>MEASUREMENTS: The primary outcome was change in Fatigue Severity Scale (FSS) score.<br><br>RESULTS: Fluvoxamine showed a significant reduction in fatigue compared with placebo at day 60 (mean difference, -0.43 [95% credible interval {CrI},
-0.80 to -0.07]), with a sustained effect at day 90 (mean difference, -0.58 [CrI, -0.98 to -0.16]). Fluvoxamine also improved quality-of-life scores with high posterior probability. Metformin showed no significant benefit. Adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%). Grade 3 and higher adverse events were rare across all groups.<br><br>LIMITATIONS: The 90-day follow-up period limits conclusions about the durability of treatment effects, and the exclusive focus on fatigue as the primary outcome does not address other prevalent long COVID symptoms, leaving fluvoxamine's broader therapeutic utility uncertain.<br><br>CONCLUSION: Fluvoxamine, but not metformin, may be an effective treatment for reducing fatigue and improving quality of life in patients with long COVID.<br><br>PRIMARY FUNDING SOURCE: The Latona Foundation.},
}
@article {pmid41911555,
year = {2026},
author = {},
title = {Summary for Patients: Fluvoxamine and Metformin for Fatigue in Patients With Long COVID.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-03959-PS},
pmid = {41911555},
issn = {1539-3704},
}
@article {pmid41903103,
year = {2026},
author = {Thakkar, K and Thamaree, R and Kyaw, MH and Chirila, I and Mendoza, CF and Dodd, J and Yarnoff, B and Kiertiburanakul, S},
title = {Potential Public Health Impact of Updated COVID-19 Vaccination Strategies in Thailand: Epidemiological Data Update.},
journal = {Pulmonary therapy},
volume = {},
number = {},
pages = {},
pmid = {41903103},
issn = {2364-1746},
abstract = {INTRODUCTION: This study evaluates the anticipated health and economic effects of multiple COVID-19 vaccination strategies using an updated vaccine in Thailand.<br><br>METHODS: A previously published hybrid decision tree and Markov model, originally developed for the USA, was calibrated using Thailand-specific epidemiological, demographic, and economic data from 2024. The model assessed several age- and risk-based vaccination strategies assuming vaccine uptake ranging from 20% to 50%. Health outcomes (cases, hospitalizations, deaths, and long COVID cases) and economic outcomes (long COVID costs, direct medical costs, and productivity losses) were projected from payer and societal perspectives. Vaccine effectiveness was assumed to be 50% against infection, 60% against symptoms, and 70% against severe disease, with a 6-month duration of protection.<br><br>RESULTS: Vaccinating individuals aged 60&#xa0;years and above and high-risk individuals aged 6&#xa0;months to 59&#xa0;years was projected to prevent 318,700 infections, 9147&#xa0;hospitalizations, and 1061 deaths in 1&#xa0;year. This strategy was estimated to yield THB 3300&#xa0;million in direct medical cost savings and THB 2695&#xa0;million in productivity loss savings. Increasing coverage in this population to 50% could amplify these reductions by up to 150%.<br><br>CONCLUSIONS: With updated Thai data, analyses suggest that use of an adapted COVID-19 vaccine could continue to generate considerable public-health and economic gains, particularly when coverage among older adults and high-risk groups is expanded. These findings carry implications for sustaining preparedness and guiding national vaccination policy.},
}
@article {pmid41903617,
year = {2026},
author = {Katsarou, MS and Papasavva, M and Tsolakou, A and Christodoulou, A and Antonoglou, A and Raptis, A and Kontaxakis, A and Gavrielatos, M and Michalopoulos, I and Vassiliou, AG and Stefanatou, M and Pappas, G and Moschos, SA and Drakoulis, N and Katsaounou, P},
title = {Clinically Confirmed Cohort Reveals Antioxidant Genetic Polymorphisms as Potential Susceptibility Factors for Long COVID After Mild or Asymptomatic COVID-19.},
journal = {Free radical biology &amp; medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.03.064},
pmid = {41903617},
issn = {1873-4596},
abstract = {Although the COVID-19 pandemic has now been down-graded, long COVID (LC) presents an ongoing risk of long-term disease for a significant percentage of the population, even after mild or no symptoms upon infection. LC post-viral effects have been associated with oxidative stress (OS), impacting canonical cell function. The aim of this study was to investigate the association of eight OS-related single nucleotide polymorphisms (SNPs) on LC susceptibility among patients with mild or no symptoms after SARS-CoV-2 infection, with emphasis on a clinically homogeneous population free from bias and overlap with other conditions. Blood samples were collected from 85 clinically confirmed LC patients and 96 unvaccinated controls (observational case control study) all with mild/asymptomatic infection, and analysed by targeted SNP genotyping in the GSTP1, SELENOS, CAT, SOD2, and EPHX1 OS-related genes. Τhe control individuals had been infected at least 6 months prior to enrollment and had not developed any symptoms related to long COVID. Our analysis revealed associations between SOD2 and EPHX1 polymorphisms and disease progression, with pre-existing thyroid disease and acute phase symptoms being significant aggravating factors. Machine Learning (ML) analysis produced a 10-factor predictive model for LC with a balanced accuracy over 0.74, released herein as an open-access LC risk rating webtool. Our findings suggest that individuals' genetic antioxidant capacity may plays an important role in long covid, fitting with current ideas of mitochondrial dysfunction and viral persistence. It is also shown how well diagnosed and bias free cohorts can reveal patterns often missed in self-reported cases and the potential for predictive tools that combine genetic and clinical data.},
}
@article {pmid41904442,
year = {2026},
author = {Martoreli Júnior, JF and Sousa, LRM and Pedroso, AO and Lima, LDES and Gusmão, CMP and Zamarioli, CM and Menegueti, MG and de Oliveira E Silva, AC and Ferreira, GRON and Gir, E and Reis, RK},
title = {Prevalence and predictive factors of long COVID in nurses in Brazil.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13176-y},
pmid = {41904442},
issn = {1471-2334},
}
@article {pmid41905866,
year = {2026},
author = {Qiu, W},
title = {Comment on "association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers".},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125883},
doi = {10.1016/j.jns.2026.125883},
pmid = {41905866},
issn = {1878-5883},
}
@article {pmid41898534,
year = {2026},
author = {Krüger, AL and Schmidt, F and Bloch, W and Haiduk, B and Grau, M},
title = {Personalized Exercise Training Modulates Red Blood Cell Rheology and Morphology in Long COVID.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
doi = {10.3390/ijms27062671},
pmid = {41898534},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/blood/therapy/physiopathology ; Male ; Female ; *Erythrocytes/pathology/cytology ; Middle Aged ; Erythrocyte Deformability ; *Exercise/physiology ; Adult ; Pilot Projects ; Longitudinal Studies ; SARS-CoV-2 ; Erythrocyte Aggregation ; Rheology ; Aged ; Hemorheology ; *Exercise Therapy/methods ; },
abstract = {Long COVID is associated with persistent fatigue, exercise intolerance, and microcirculatory dysfunction. Altered red blood cell (RBC) rheology, including impaired deformability and increased aggregation, may contribute to these symptoms, yet the effects of exercise interventions remain unclear. This longitudinal pilot study tested whether an individualized, symptom-responsive exercise program improves RBC rheology in Long COVID. A total of 170 (110 f/60 m) participants entered a five-phase training protocol; 15 completed all phases and formed a predefined finisher subgroup. RBC aggregation and deformability, hematological parameters, and coagulation- and iron-related markers were assessed across phases; RBC morphology was additionally analyzed in finishers at baseline and completion. In the total cohort, aggregation indices decreased across training phases, accompanied by prolonged aggregation half-time, while hematological, coagulation, and iron markers remained largely unchanged. The deformability changes were not uniform in the full cohort; however, finishers showed a deformability shift after completion. Importantly, morphologically abnormal RBC decreased in finishers, and these changes correlated with deformability, suggesting that improved rheology is linked to reduced RBC abnormalities. Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits.},
}
@article {pmid41899098,
year = {2026},
author = {Wang, J and Liu, L and Zhou, N and Zhang, Y and Liu, H and Xu, C and Wu, Y and Zhang, J},
title = {The Clinical Research of the Chronic Cough After COVID-19 Infection.},
journal = {Journal of clinical medicine},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/jcm15062174},
pmid = {41899098},
issn = {2077-0383},
abstract = {Objective: To investigate the epidemiology, clinical characteristics, and potential risk factors of chronic cough following SARS-CoV-2 infection. Methods: A total of 1434 patients with post-COVID-19 cough were categorized into acute, subacute, and chronic subgroups by cough duration, with clinical data analyzed across subgroups. Questionnaire surveys were conducted in chronic cough patients, followed by an 18-21-month follow-up. Results: 1. Significant intergroup differences were observed among the three groups in: the number of patients with rhinitis and/or pharyngitis history, cough with chest tightness, cough with pharyngeal symptoms, and sensitivity to irritating odors and cold air. 2. The chronic group had a significantly lower platelet count but higher eosinophil and basophil percentages than the acute group. 3. The chronic group showed significantly lower values than the subacute group in multiple pulmonary function indices: FVC, FEV1, FEV1/FVC, PEF, MEF25, MEF75, MEF50, MMEF75/25, MEF75%, MEF50%, MEF25%, MMEF75/25%, DLCO, and DLCO%. 4. Chest CT findings: the chronic group had significantly lower rates of infected lesions, cord-like opacities, and ground-glass shadows than the acute group, but a higher rate of micro-nodules than the subacute group. 5. At follow-up, the cough and non-cough groups differed significantly in nighttime cough scores and the proportion of cough with chest tightness, as well as in pulmonary function parameters: FVC, FEV1, PEF, PEF%, MEF75, DLCO, RV% and TLC. 6. Binary logistic regression analysis identified the nocturnal cough symptom score and cough accompanied by chest tightness as independent factors influencing persistent cough 18-21 months after SARS-CoV-2 infection. Conclusions: Patients with pre-existing upper airway inflammation, laryngeal symptoms, chemical hypersensitivity, elevated eosinophil/basophil percentages, and pulmonary micro-nodules are more likely to develop chronic post-COVID cough, presenting with partial ventilatory impairment and diffusing capacity impairments.},
}
@article {pmid41899187,
year = {2026},
author = {Miwa, K},
title = {Disequilibrium, Rather than Postural Orthostatic Tachycardia Syndrome, Is the Primary Determinant of Orthostatic Intolerance in Patients with Long COVID.},
journal = {Journal of clinical medicine},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/jcm15062263},
pmid = {41899187},
issn = {2077-0383},
abstract = {Background: Orthostatic intolerance (OI) is an important factor affecting daily functional capacity in patients with long COVID. Traditionally, most OI symptoms have been attributed to exaggerated sympathetic nervous system activation associated with postural orthostatic tachycardia syndrome (POTS). Disequilibrium, also referred to as postural instability, may contribute to the development of OI in patients with long COVID. Methods: This study evaluated 32 patients with long COVID using neurological examinations and the active 10-min standing test. Disequilibrium was assessed using the Romberg and tandem gait tests. OI was defined as the inability to complete the active 10-min standing test. Results: Seven patients (22%) were diagnosed with OI. None of them had POTS, whereas six (86%) demonstrated disequilibrium, as detected by the Romberg and/or tandem gait test. POTS was observed in eight patients (25%), none of whom had OI. Disequilibrium was observed in nine patients (28%), six of whom (67%) had OI. Multiple regression analysis revealed that disequilibrium was positively associated with OI (r = 0.64, p < 0.001), whereas POTS was inversely associated (r = -0.38, p < 0.05). After 6 weeks of oral minocycline treatment in six patients and 2 weeks of repetitive transcranial magnetic stimulation therapy following minocycline in the other one patient, symptom amelioration was reported in six patients with OI. OI concomitant with disequilibrium recovered in five of the six patients treated and tested, although one patient who experienced symptom recovery failed to undergo the repeated standing test. Conclusions: Disequilibrium, rather than POTS, was the primary determinant of OI in patients with long COVID.},
}
@article {pmid41899272,
year = {2026},
author = {Suárez-Moreno, N and Gómez-Sánchez, L and Arroyo-Romero, S and Navarro-Cáceres, A and Domínguez-Martín, A and Lugones-Sánchez, C and González-Sánchez, S and Sánchez-Moreno, A and Rodríguez-Sánchez, E and García-Ortiz, L and Gómez-Marcos, MA and Gómez-Sánchez, M and Navarro-Matias, E},
title = {Association Between Metabolic Syndrome Components and Vascular Structure and Function in Subjects with a Diagnosis of Long COVID: The BioICOPER Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/jcm15062348},
pmid = {41899272},
issn = {2077-0383},
support = {PI25/00071//Instituto de Salud Carlos III/ ; GRS 2707/C/24; GRS 3007/C/2024//The government of Castilla y Le&#xf3;n/ ; },
abstract = {Background: Long COVID is characterised by persistent symptoms after SARS-CoV-2 infection, and its impact on cardiovascular health is a growing concern. This study aimed to evaluate the association between the presence and severity of metabolic syndrome and vascular structural and functional in patients with long COVID. Methods: We conducted a cross-sectional study of 304 adults diagnosed with long COVID. Vascular health was assessed using carotid intima-media thickness to evaluate arterial structure, and pulse wave velocity to assess arterial stiffness. Metabolic syndrome was defined according to international criteria. Multiple regression models were performed to analyse the association between the number of metabolic syndrome components and vascular parameters, adjusting for age, sex, lifestyle and pharmacological treatments. Results: All vascular measures show a positive association with artery pressure. All measures except cardio-ankle vascular index were positively associated with the number of metabolic syndrome components. Carotid intima-media thickness, carotid-femoral pulse wave velocity and vascular ageing index were positively associated with waist circumference. Brachial-ankle pulse wave was positively associated with all metabolic syndrome components and showed an inverse association with HDL-cholesterol. Cardio-ankle vascular index was inversely associated with waist circumference. Conclusions: In conclusion, among adults with long COVID, metabolic syndrome and the accumulation of its components are associated with poorer vascular structure, function, and vascular ageing.},
}
@article {pmid41900303,
year = {2026},
author = {Hommos, L and Gohil, H and Rob, M and Manyama, J and Ramy, H and Naseem, N and Nishan, H and Ibrahim, RS and Ibrahim, SS and Njoku, VCE and Al-Mutawa, I and Khan, AF and Holroyd, S and Zakaria, D},
title = {Long-Term Thyroid Complications Post-COVID-19: A Systematic Review.},
journal = {Microorganisms},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/microorganisms14030543},
pmid = {41900303},
issn = {2076-2607},
abstract = {Coronavirus disease 2019 (COVID-19) is increasingly shown to be a multisystem disorder with long-term complications, including endocrine system complications. The thyroid gland is also susceptible, as it contains ACE2 receptors, making it exposed to both direct viral damage and autoimmune-mediated dysfunction. Recent reports document the various thyroid complications that persist well after the acute infection phase. This systematic review investigates the long-term thyroid complications in individuals with a history of SARS-CoV-2 infection. A comprehensive literature search across several databases was conducted. Eligible studies reported new onset long-term thyroid complications occurring post-COVID-19 infection. Abstract and full-text screening as well as data extraction and quality assessment was performed by two independent reviewers. Only 28 studies met our inclusion criteria, reporting 419 patients from 18 countries. These studies included case reports, case series, cohort, and cross-sectional studies. Reported thyroid disorders included subacute thyroiditis, thyrotoxicosis, hyperthyroidism (including Graves' disease), isolated high T3/T4, hypothyroidism, central hypothyroidism, and non-thyroidal illness syndrome (NTIS). While many of these eventually resolved, a significant portion persisted or recurred, especially autoimmune thyroiditis. COVID-19 is associated with a range of long-term thyroid complications. Although some cases are temporary, others last, especially autoimmune thyroid disorders. Proposed mechanisms include direct viral cytotoxicity, cytokine-mediated Hypothalamic-Pituitary-Thyroid (HPT) axis suppression, post-viral autoimmunity, vascular injury, and neuroendocrine disruption. Routine thyroid function monitoring in COVID-19 survivors, particularly those with severe disease or persistent symptoms is recommended, and larger prospective studies are needed to better understand incidence and outcomes.},
}
@article {pmid41890193,
year = {2026},
author = {Zhu, B and Qu, S and Li, J and Deng, W and Shen, WJ and Chen, J},
title = {The mechanisms underlying COVID-19 induced insulin resistance: a narrative review.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1781679},
pmid = {41890193},
issn = {1664-2392},
mesh = {Humans ; *Insulin Resistance/physiology ; *COVID-19/complications/metabolism ; SARS-CoV-2 ; Gastrointestinal Microbiome ; Diabetes Mellitus/etiology/metabolism ; },
abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in a significant increase in insulin resistance and new-onset diabetes among recovered individuals. This review examines the multifactorial mechanisms underlying these metabolic complications, including activation of the immune system and inflammatory cascades, lifestyle changes, nutritional deficiencies, imbalances in amino acid metabolism, alterations in ketogenesis, disruptions in the gut microbiome, psychological impacts, and COVID-19 vaccines. We discuss how these factors collectively contribute to insulin resistance, particularly in the context of COVID-19, and highlight potential therapeutic strategies, such as dietary interventions and ACE2 activators, that may mitigate these effects. Our analysis underscores the need for targeted approaches to prevent and treat insulin resistance in post-COVID-19 patients, emphasizing the importance of understanding the pandemic's long-term metabolic consequences.},
}
@article {pmid41890992,
year = {2026},
author = {Chakravarty, D and Dandekar, R and Lashkari, VD and Tilton, I and McAlpine, L and Chiarella, J and Nelson, A and Ngo, T and Chen, P and Wang, G and Saxena, A and Castillo-Rojas, B and Zorn, K and Tribble, DR and Burgess, TH and Rubin, LH and Richard, SA and Agan, BK and Pollett, SD and Farhadian, S and Spudich, S and Pleasure, SJ and Wilson, MR},
title = {Autoantibody landscapes in neurological Long COVID and post-COVID cognitive impairment show heterogeneity without a shared disease signature.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.19.26348833},
pmid = {41890992},
abstract = {BACKGROUND: Neurological Long COVID (n-LC) includes persistent cognitive and autonomic symptoms after SARS-CoV-2 infection. Prior studies of post-COVID conditions have described diverse humoral autoreactivity, but findings are heterogeneous, and it remains unclear whether n-LC is associated with a consistent CNS-directed humoral signature.<br><br>METHODS: We performed a cross-cohort case-control analysis to detect autoantibodies in cerebrospinal fluid (CSF) and serum from n-LC participants. In the Yale COVID Mind Study cohort, CSF from n-LC participants and from pre-pandemic and post-COVID asymptomatic controls was assessed by mouse brain immunofluorescence and proteome-wide phage immunoprecipitation sequencing (PhIP-Seq), with candidate reactivities evaluated by orthogonal assays and supervised modeling. In the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (IDCRP EPICC) cohort, post-COVID sera collected prior to iPhone- or iPad-based cognitive screening were profiled by PhIP-Seq and compared between participants with and without cognitive impairment.<br><br>RESULTS: CSF immunoreactivity on mouse brain tissue was observed in both n-LC and controls, with similar overall frequencies, although n-LC participants more often showed nuclear-predominant staining patterns. PhIP-Seq identified sparse, largely patient-specific peptide reactivities to nuclear and neuronal proteins in CSF and serum. Supervised models provided limited discrimination between cases and controls. Candidate autoantigens had limited disease specificity on orthogonal testing. EPICC serum autoantibody profiling similarly failed to distinguish individuals with and without cognitive impairment.<br><br>CONCLUSIONS: Across cohorts and compartments, n-LC did not exhibit a shared autoantibody signature. These findings support the absence of a dominant, common CNS autoantibody-mediated mechanism in n-LC.<br><br>FUNDING: Grants HU00012020067, HU00012120103, HU00011920111, R01NS125693, R01MH125737, R01AI157488 from Defense health program and NIH.},
}
@article {pmid41891379,
year = {2026},
author = {Babaeipour, R and Fox, MS and Parraga, G and Ouriadov, A},
title = {Benchmarking Hybrid CNN-Transformer Versus Pure Transformer Architectures for Accelerated Hyperpolarized [129]Xe MRI Reconstruction.},
journal = {Journal of magnetic resonance imaging : JMRI},
volume = {},
number = {},
pages = {},
doi = {10.1002/jmri.70314},
pmid = {41891379},
issn = {1522-2586},
support = {R9245A04//Natural Sciences and Engineering Research Council of Canada/ ; },
abstract = {BACKGROUND: Hyperpolarized [129]Xe MRI faces technical challenges including low signal-to-noise ratio and breath-hold constraints. Current literature focuses on proprietary deep learning methods or image-domain enhancements.<br><br>PURPOSE: To present a comprehensive evaluation of transformer and hybrid CNN-transformer architectures integrating dual-domain (k-space and image) processing for HP [129]Xe MRI reconstruction.<br><br>STUDY TYPE: Retrospective.<br><br>POPULATION: Two hundred five participants (22 healthy [male and female, 18-85&#x2009;years], 26 COPD [male and female, 50-85&#x2009;years], 90 asthma [male and female, 18-70&#x2009;years], 67 long-COVID [male and female, 18-70&#x2009;years]) yielding 1640 2D slices. Dataset split: 80% training (1312 slices), 10% validation (164 slices), 10% test (164 slices).<br><br>FIELD STRENGTH/SEQUENCE: 3&#x2009;T; 3D fast gradient-recalled echo.<br><br>ASSESSMENT: Five architectures were compared: KTMR (hybrid transformer-CNN), KIKI-net (pure CNN), ReconFormer, SwinMR, and MR-IPT (pure transformer) at acceleration factors of 3, 7, and 10. Performance was assessed using peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), and normalized mean squared error (NMSE). Ventilation defect percentage (VDP) agreement with semi-automated analysis was evaluated.<br><br>STATISTICAL TESTS: Friedman test with post hoc Dunn's test and Benjamini-Hochberg correction for multiple comparisons. Significance level: p&#x2009;<&#x2009;0.05.<br><br>RESULTS: At 10-fold acceleration, KTMR produced PSNR of 36.4&#x2009;&#xb1;&#x2009;2.8&#x2009;dB and SSIM of 0.88&#x2009;&#xb1;&#x2009;0.12, significantly outperforming KIKI-net (32.5&#x2009;&#xb1;&#x2009;3.4&#x2009;dB, 0.81&#x2009;&#xb1;&#x2009;0.12), ReconFormer (29.7&#x2009;&#xb1;&#x2009;2.6&#x2009;dB, 0.76&#x2009;&#xb1;&#x2009;0.12), SwinMR (30.5&#x2009;&#xb1;&#x2009;2.8&#x2009;dB, 0.76&#x2009;&#xb1;&#x2009;0.09), and MR-IPT (28.8&#x2009;&#xb1;&#x2009;2.4&#x2009;dB, 0.74&#x2009;&#xb1;&#x2009;0.11). VDP measurements showed mean bias of 1.94% at 3-fold, 2.12% at 7-fold, and 2.69% at 10-fold acceleration.<br><br>DATA CONCLUSION: KTMR demonstrated superior performance for HP [129]Xe MRI reconstruction at high acceleration factors.<br><br>EVIDENCE LEVEL: 3.<br><br>TECHNICAL EFFICACY: Stage 1.},
}
@article {pmid41892619,
year = {2026},
author = {Guzmán Priego, CG and Villalpando, JMG and Baeza Flores, GDC and Ble Castillo, JL and Celorio Méndez, KDS and Juárez Rojop, IE and Martínez López, MC and López Villarreal, SM and Rodríguez Luis, OE and Quiroz Gómez, S and Romero Tapia, SJ and García Orozco, JM and López Nácar, WS and Salinas Terrazas, OO and Jiménez Aragón, KA},
title = {Cognitive and Neuropsychiatric Sequelae After SARS-CoV-2 Infection: A Narrative Review and Exploratory Cross-Sectional Study of Neurofilament Light Chain and GFAP.},
journal = {Brain sciences},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/brainsci16030276},
pmid = {41892619},
issn = {2076-3425},
abstract = {Background: Persistent cognitive and neuropsychiatric symptoms have been increasingly reported as part of the post-COVID-19 condition. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are circulating biomarkers of neuronal and astrocytic injury that increase during acute SARS-CoV-2 infection; however, their role in long-term neuropsychiatric sequelae remains unclear. Objective: To provide a narrative overview of cognitive and neuropsychiatric sequelae following SARS-CoV-2 infection and to explore the association of plasma NfL and GFAP concentrations with cognitive impairment and neuropsychiatric symptoms in individuals recovered from COVID-19. Methods: A narrative review of the literature was conducted, followed by an exploratory cross-sectional study including 41 adults recovered from SARS-CoV-2 infection. Participants were classified according to acute disease severity into two groups. Cognitive function was assessed using MoCA, and neuropsychiatric symptoms were evaluated using DASS-21. Plasma NfL and GFAP concentrations were measured by ELISA. Group comparisons and Spearman correlation analyses were performed. Results: A total of 41 individuals were studied; they recovered from moderate or severe COVID-19 and exhibited a higher prevalence of cognitive impairment and neuropsychiatric symptoms compared with those who recovered from mild or asymptomatic infection. Plasma NfL and GFAP concentrations did not differ significantly between severity groups. NfL showed a weak association with the presence of post-COVID-19 condition. Conclusions: This study highlights the high burden of persistent cognitive and neuropsychiatric symptoms following moderate and severe SARS-CoV-2 infection. The absence of sustained elevations in circulating NfL and GFAP nearly two years after infection suggests that ongoing symptoms may involve mechanisms beyond overt neuronal or astrocytic injury.},
}
@article {pmid41895458,
year = {2026},
author = {Fehrer, A and Windzio, L and Schoening, S and Steiner, S and Aschenbrenner, AC and Babel, N and Behrends, U and Bellmann-Strobl, J and Cammà, G and Cash, A and Doehner, W and den Dunnen, J and Fluge, &#xd8; and Franke, C and Hoffmann, K and Kedor, C and Kim, L and Löhden, W and Mella, O and Mihatsch, LL and Peluso, MJ and Puta, C and Putrino, D and Ramoji, A and Sato, W and Sawitzki, B and Schlieper, G and Schoenfeld, Y and Seifert, M and Sigurdsson, F and Slaghekke, A and Sommerfelt, K and Sotzny, F and Stein, E and Steinacker, JM and Stingl, M and Systrom, DM and Tronstad, KJ and Wirth, K and Wörmann, B and Wüst, RCI and Yamamura, T and Scheibenbogen, C},
title = {Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3[rd] International Conference of the Charité Fatigue Center.},
journal = {Autoimmunity reviews},
volume = {},
number = {},
pages = {104043},
doi = {10.1016/j.autrev.2026.104043},
pmid = {41895458},
issn = {1873-0183},
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3[rd] International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.},
}
@article {pmid41881896,
year = {2026},
author = {Nakase, T},
title = {Response to the letter of the editor on "association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers".},
journal = {Journal of the neurological sciences},
volume = {485},
number = {},
pages = {125882},
doi = {10.1016/j.jns.2026.125882},
pmid = {41881896},
issn = {1878-5883},
}
@article {pmid41882228,
year = {2026},
author = {Zeidan, RK and Al-Bluwi, N and Shukla, A and AlZubaidi, H and Awad, M and Hussein, A and Agha, R and Othman, D and Sharif, FMJ and Hussein, AC and Mahmoud, S and Obaideen, A and Younes, SB and AbuEbaid, M and Obaideen, AM and AlHano, Z and Mohammed, G and AlHajjaj, M and Halwani, R and Saddik, B},
title = {Symptoms, risk factors, and health outcomes of long COVID in the United Arab Emirates.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44682-3},
pmid = {41882228},
issn = {2045-2322},
support = {Grant code:150389//University of Sharjah/ ; },
}
@article {pmid41883772,
year = {2026},
author = {Jain, A and Saraswat, P and Sharma, A and Sharma, V and Jain, R},
title = {Persistent health complications in COVID-19 hospitalized patients at tertiary care hospital in Western India.},
journal = {World journal of critical care medicine},
volume = {15},
number = {1},
pages = {114620},
pmid = {41883772},
issn = {2220-3141},
abstract = {BACKGROUND: Long coronavirus disease (COVID) is a condition characterized by persistent health issues following severe acute respiratory syndrome coronavirus 2 infection. The condition remains poorly understood, especially in terms of long-term impact on health and the quality of life. This study hypothesized that majority of the discharged patients experience long-term post-COVID-19 complications.<br><br>AIM: To evaluate the long-term post-COVID-19 complications and its impact on the patients' quality of life.<br><br>METHODS: This retrospective cohort study, with telephonic interview-based follow-up, was conducted at a tertiary care hospital in western India between March and August 2024. The medical records of the patients hospitalized with COVID-19 during the second wave (between March and June 2021) and discharged, were reviewed. The data were collected from the patients via structured telephonic interviews that focused on post-infection sequelae across various bodily systems and was summarized using percentages and proportions.<br><br>RESULTS: A total of 1139 patients who met the inclusion criteria, participated in the study with a follow-up period of three years. Amongst the survivors (n = 1052) at the end of three years, 150 (14.25%) developed new or ongoing diseases after recovery from acute COVID-19, while 51 (4.8%) were still under treatment at the time of follow-up. Amongst these 150 long-COVID-19 patients, pulmonary disease (n = 27, 2.57%), body pain (n = 20, 1.90%), coronary artery disease or angioplasty, and diabetes mellitus (n = 17, 1.61% each), hypertension (n = 16, 1.52%), and fatigue (n = 13, 1.24%) were frequently reported. Although statistically insignificant, the patients who received three or more vaccine doses after the second wave of the pandemic reported slightly lower rates of post-COVID-19 morbidity and treatment requirements.<br><br>CONCLUSION: The current study highlights the burdens of long-term complications following COVID-19 infection, with a broad spectrum of post-infection sequelae. However, the impact of vaccination on the course of development and treatment of long COVID could not be ascertained. This finding emphasizes the need for continued research and healthcare planning to address the persistent impact of COVID-19 upon the survivors.},
}
@article {pmid41883830,
year = {2026},
author = {Chu, X and Hou, S and Zhu, Q and Chang, J and Gong, L and Wu, J},
title = {Analysis of Long COVID characteristics and risk factors in individuals infected with COVID-19: a follow-up study based on a cohort of 2,792 participants.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1760355},
pmid = {41883830},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/blood ; Male ; Female ; Middle Aged ; Risk Factors ; Follow-Up Studies ; Adult ; Prospective Studies ; SARS-CoV-2 ; Aged ; China/epidemiology ; },
abstract = {BACKGROUND: Since the emergence of SARS-CoV-2 in 2019, Long COVID has emerged as a significant global public health challenge. The identification of accessible biomarkers and risk factors is critical to enabling early intervention and improving long-term outcomes.<br><br>METHODS: This prospective cohort study enrolled 2,792 individuals with confirmed COVID-19 from Anhui Province in September 2024. A propensity score matching analysis was performed using a 1:4 ratio. Cases and matched controls were selected from cohort, serum sample were analyzed to assess hematological parameters. Multivariable logistic regression models were applied to identify independent risk factors associated with the development of Long COVID.<br><br>RESULTS: 2,792 participants (average age 51.64 years) identified 182 (6.52%) long COVID patients during follow-up. Common symptoms included fatigue, cough, insomnia, throat discomfort, and appetite loss. After propensity score matching, risk factors were age, more severe acute symptoms. Long COVID patients exhibited higher red blood cell counts but lower hemoglobin-related indices and platelet count.<br><br>CONCLUSION: This study confirms the persistent risk of Long COVID following reinfection, with heightened susceptibility associated with advanced age, specific acute-phase symptoms. Alterations in routine hematological parameters may serve as valuable biomarkers for the monitoring and management of Long COVID.},
}
@article {pmid41883910,
year = {2026},
author = {Montoya, S and Alvarez Ramirez, D and Chavarría, R and Zamora, EL and Soto Cordero, CA},
title = {Anesthesia in Patients With Long COVID or Post-infectious Respiratory Sequelae Undergoing Emergency Surgery: Clinical Challenges and Perioperative Strategies.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104067},
pmid = {41883910},
issn = {2168-8184},
abstract = {The COVID-19 pandemic has left lasting health consequences that extend beyond the acute infection phase, with long COVID emerging as a complex multisystem condition that poses significant challenges in the perioperative setting. Patients with post-infectious respiratory or cardiovascular sequelae present an increased anesthetic risk due to persistent inflammation, pulmonary fibrosis, reduced lung compliance, and myocardial dysfunction. These alterations predispose to hypoxemia, arrhythmias, and hemodynamic instability during surgery, making preoperative assessment and individualized anesthetic planning essential. Comprehensive evaluation, including functional tests, cardiac and pulmonary imaging, and laboratory analysis, allows early identification of residual organ dysfunction that can compromise perioperative safety. Anesthetic management must be adapted to the patient's physiological condition, emphasizing lung-protective ventilation, cautious fluid therapy, and close hemodynamic monitoring. Regional anesthesia is preferred when feasible to minimize airway manipulation and reduce respiratory complications, while total intravenous anesthesia represents a safer option when general anesthesia is required. Postoperative care focuses on extended respiratory monitoring, multimodal analgesia to limit opioid use, and the implementation of pulmonary physiotherapy and antithrombotic prophylaxis to prevent complications. Psychological support is also recommended to address post-COVID anxiety and fatigue, contributing to holistic recovery. Although clinical guidelines provide useful recommendations, current evidence remains limited and heterogeneous. Further research is required to clarify the pathophysiological mechanisms of long COVID, evaluate anesthetic drug interactions, and develop validated risk stratification tools. Establishing standardized, evidence-based perioperative protocols is essential to improve outcomes and ensure patient safety in individuals with long COVID undergoing emergency surgery.},
}
@article {pmid41884491,
year = {2026},
author = {Ayoubkhani, D and Atchison, CJ and Banerjee, A and Brightling, C and Calvert, M and Diamond, I and Eggo, RM and Elliott, P and Evans, RA and Haroon, S and Herrett, E and Nafilyan, V and O'Mahoney, LL and Pinto Pereira, SM and Routen, A and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Zaccardi, F and Khunti, K},
title = {Considerations for epidemiological studies investigating emerging post-acute infection syndromes: Long Covid as a case study.},
journal = {EClinicalMedicine},
volume = {94},
number = {},
pages = {103833},
pmid = {41884491},
issn = {2589-5370},
abstract = {Epidemiological research studies into Long Covid, currently defined by prolonged symptoms after SARS-CoV-2 infection, have reported widely varying prevalence estimates. As well as rapidly evolving scientific knowledge of Long Covid, these differences are partly driven by substantial methodological heterogeneity between studies, including the outcome definition of Long Covid; duration of follow-up; study design, period and population; sampling frame; data source; and the statistical techniques employed. Having a robust understanding of the prevalence of and risk factors for Long Covid is essential for informing treatment pathways, service provision and policy decisions. In preparation for the public health response to future epidemics and pandemics, this review outlines key epidemiological and statistical considerations and recommendations when designing studies of emerging post-acute infection syndromes, focussing on Long Covid as a case study.},
}
@article {pmid41884792,
year = {2026},
author = {Yamamoto, K and Iwanaga, N and Umemura, A and Sawai, T and Sumiyoshi, M and Hashiguchi, K and Mori, Y and Ishii, H and Futsuki, Y and Kiyohara, M and Ota, K and Kosai, K and Sasaki, D and Takamatsu, Y and Inoue, S and Morita, K and Tsutsui, S and Ashizawa, K and Takazono, T and Sakamoto, N and Hosogaya, N and Tashiro, M and Tanaka, T and Izumikawa, K and Yanagihara, K and Mukae, H},
title = {Symptom relief and cytokine modulation by clarithromycin in mild COVID-19 pneumonia: an exploratory, multicenter, randomized-controlled open-label trial (CAME-COVID study).},
journal = {Therapeutic advances in infectious disease},
volume = {13},
number = {},
pages = {20499361261431488},
pmid = {41884792},
issn = {2049-9361},
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator.<br><br>OBJECTIVES: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease.<br><br>DESIGN: An exploratory, multicenter, randomized-controlled, open-label trial.<br><br>METHODS: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations.<br><br>RESULTS: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C (p = 0.08), and fatigue significantly decreased in group A (p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-&#x3b1;, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-&#x3b1;, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-&#x3b3; in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A.<br><br>CONCLUSION: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia.<br><br>TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011) on April 13, 2021.},
}
@article {pmid41887765,
year = {2026},
author = {Wing, K and Morton, C and Mahalingasivam, V and Costello, RE and Cowling, T and Lin, LY and Inglesby, P and Walker, A and , and , and Bacon, S and Mehrkar, A and Goldacre, B and Evans, S and Douglas, I and Eggo, R and Tomlinson, L and Mansfield, KE},
title = {Occurrence and persistence of symptoms, diagnoses and prescriptions after community-diagnosed COVID-19: a matched cohort study using the OpenSAFELY platform.},
journal = {Journal of epidemiology and community health},
volume = {},
number = {},
pages = {},
doi = {10.1136/jech-2025-225474},
pmid = {41887765},
issn = {1470-2738},
abstract = {BACKGROUND: We aimed to explore the occurrence and persistence of symptoms, diagnoses and prescribing after COVID-19 among populations from earlier (wave 2) and later (wave 4) in the pandemic.<br><br>METHODS: With the approval of NHS England, we analysed data from English primary care using The Phoenix Partnership SystmOne through the OpenSAFELY data analytics platform. Individuals with community-diagnosed COVID-19 September 2020-January 2021 (wave 2) were matched to contemporary (2020-2021)&#x2009;and historical (2017-2018) comparators. Individuals with community COVID-19 December 2021-March 2022 (wave 4) were matched to contemporary comparators (last follow-up 31 March 2023). Occurrence of each of (1) long-COVID symptoms; (2) primary-care diagnoses and (3) new prescriptions was analysed at any time during 1 year after COVID-19 and at: 4-12 weeks, 12&#x2009;weeks-6 months and 6&#x2009;months-12 months after COVID-19 to assess persistence.<br><br>RESULTS: 902 885 COVID-19 cases (wave 2) matched to 4&#x2009;449&#x2009;265 contemporary (no-COVID-19) comparators. 1 553 160 COVID-19 cases (wave 4) matched to 7&#x2009;624&#x2009;770 contemporary comparators. Positive wave 2 associations after COVID-19 were observed for hair loss (OR 1.57, 95%&#x2009;CI 1.48 to 1.66), mobility impairment (1.41, 1.35 to 1.48), fatigue (1.46, 1.42 to 1.49), cognitive impairment (1.39, 1.34 to 1.44) and loss of taste or smell (1.38, 1.31 to 1.46). At 6-12 months reporting persisted for mobility impairment, fatigue and cognitive impairment. There were small increases in new prescriptions for NSAIDs (1.24, 1.23 to 1.26), drugs to treat infections (1.24, 1.23 to 1.25)&#x2009;and musculoskeletal problems (1.23, 1.22 to 1.25). Wave 4 associations were generally weaker than Wave 2.<br><br>CONCLUSIONS: Long-COVID symptoms and new prescribing generally reduce over time and are potentially less problematic following less severe illness. Fatigue/cognitive/mobility symptoms persist following COVID-19.},
}
@article {pmid41876769,
year = {2026},
author = {Azhir, A and Cheng, J and Tian, J and Murphy, SN and Estiri, H},
title = {Paxlovid shows organ-specific and age-specific impacts on risk of developing post-acute sequelae of COVID-19.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01535-4},
pmid = {41876769},
issn = {2730-664X},
support = {R01AI165535//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {BACKGROUND: The impact of antiviral therapies, including Paxlovid, on post-acute sequelae of COVID-19 (PASC) remains inconclusive.<br><br>METHODS: We analyzed data from 19,413 patients (age > 18) from a validated PASC research cohort in New England who experienced at least one COVID-19 infection episode between January 1, 2022, and June 7, 2022, totaling 22,094 episodes. Multivariable logistic regression with inverse probability weights was used to infer the causal effects of Paxlovid treatment during acute infection and the risk of PASC overall (primary outcome), stratified by age group and organ system.<br><br>RESULTS: Across all age groups, Paxlovid shows no statistically significant effect in lowering overall PASC risk. Stratification by organ system reveals a 37% reduction in gastrointestinal PASC (OR: 0.63; 95% CI: [0.468, 0.850]; p&#x2009;<&#x2009;0.05) but a 97.4% increase in the risk of eye and ear-related PASC (OR: 1.974; 95% CI: [1.048, 3.718]; p&#x2009;<&#x2009;0.05). Among patients aged 65 to 75 years who were not hospitalized, Paxlovid is associated with a 16.8% reduction in PASC risk (OR: 0.832; 95% CI: [0.7, 0.989]; p&#x2009;<&#x2009;0.05). No statistically significant effects is observed for other organ-specific outcomes.<br><br>CONCLUSIONS: Paxlovid demonstrates organ-specific effects on the risk of PASC, with a reduction in gastrointestinal symptoms and an increased risk of eye and ear-related symptoms. In older, non-hospitalized patients, Paxlovid modestly reduces overall PASC risk. These findings highlight the complexity of antiviral therapy's long-term impact and underscore the need for further research to clarify the mechanisms underlying these outcomes.},
}
@article {pmid41876788,
year = {2026},
author = {Diciolla, NS and Marques, A and Jiménez-Martín, A and Alecto-Aznar, E and Torres-Lacomba, M and Yuste-Sánchez, MJ},
title = {Physical activity coaching programme for people with Long COVID: a pilot randomised clinical trial.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44806-9},
pmid = {41876788},
issn = {2045-2322},
support = {FPI-UAH-20//Universidad de Alcal&#xe1;/ ; III PI 2022/04//Professional College of Physiotherapists of the Community of Madrid/ ; },
}
@article {pmid41877909,
year = {2026},
author = {Wu, S and Huang, X and Liang, X and Liang, S and Wang, M and Hong, L and Chen, G and Wei, M and Ning, Y and He, Z},
title = {Clinical Characteristics and Glucocorticoids Efficacy in COVID-19 Patients with Type 2 Diabetes: A Multicenter Retrospective Study.},
journal = {Infection and drug resistance},
volume = {19},
number = {},
pages = {586849},
pmid = {41877909},
issn = {1178-6973},
abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) patients infected with coronavirus disease 2019 (COVID-19) are at a higher risk of experiencing poorer prognoses and increased mortality. Glucocorticoids are recommended for the treatment of COVID-19, especially in patients with severe disease. However, the efficacy and safety of glucocorticoids in COVID-19 patients with T2DM remain a subject of debate.<br><br>METHODS: We conducted a multicenter, retrospective cohort study of hospitalized patients with T2DM and confirmed COVID-19 admitted between November 1, 2022 and January 31, 2023. Data on clinical manifestations, treatment strategies, and clinical outcomes were systematically collected and rigorously evaluated.<br><br>RESULTS: A total of 624 COVID-19 patients with T2DM were enrolled, comprising 259 patients with severe disease and 365 with non-severe disease. Compared with the non-severe group, the severe group demonstrated significantly elevated levels of inflammatory markers and more extensive multi-organ dysfunction. Multivariate logistic regression identified advanced age, male sex, cerebrovascular disease history, and poor fasting glucose control as independent predictors of progression to severe illness. Among patients with severe disease, glucocorticoid therapy was significantly associated with reduced in-hospital mortality and a shorter median length of stay; this association remained robust after adjustment for baseline glycemic status. Six-month post-discharge follow-up revealed no significant between-group differences in the incidence of long COVID-19 or interstitial pneumonia; however, among patients in non-severe group, those who received glucocorticoids exhibited a higher incidence of long COVID-19.<br><br>CONCLUSION: Glucose control is of particular importance for COVID-19 patients with T2DM. In mild or moderate cases, systemic use of glucocorticoid therapy should be strictly evaluated. In severe or critical cases, cautious, appropriate use of glucocorticoids may be associated with improved short-term prognosis and reduced mortality.},
}
@article {pmid41878230,
year = {2026},
author = {Choi, S and Huda, MN and John, JR and Eapen, V},
title = {The Effectiveness of Non-Pharmacological Interventions in Treating Adolescents and Young Adults with Neuropsychiatric Symptoms of Long COVID: A Systematic Review and Meta-Analysis.},
journal = {Neuropsychiatric disease and treatment},
volume = {22},
number = {},
pages = {570223},
pmid = {41878230},
issn = {1176-6328},
abstract = {BACKGROUND: The management of persistent symptoms for long COVID (eg, fatigue, concentration difficulties, sleep difficulties, loss of appetite and taste, depression, and anxiety) has not been widely studied among adolescents and young adults (AYA). This systematic review and meta-analysis aimed to synthesise and review evidence on the effectiveness of non-pharmacological interventions for AYA aged 13-25 years, presenting with long COVID symptoms.<br><br>METHODS: A systematic literature search was conducted in four electronic databases (PubMed, EMBASE, PsycInfo, and ProQuest) in addition to manual searches for studies from January 2020 to May 2025 (PROSPERO: CRD42024516016). The studies were screened for eligibility, and methodological quality was assessed using the Joanne Briggs Institute Critical Appraisal tool by two independent reviewers. Findings were summarised using a narrative synthesis approach, and where possible, a meta-analysis was conducted using a random effects model with standardised mean differences (SMD) and a 95% confidence interval (CI).<br><br>RESULTS: Of the 325 screened articles, seven studies were included, which discussed six interventions. Three studies reported on the effectiveness of three multidisciplinary rehabilitation programs (eg, neuropsychological rehabilitation program, multidisciplinary post-COVID rehabilitation program, micro-choice-based concentrated group rehabilitation), three on alternative medicine practices (eg, forest bathing, traditional Thai Medicine), and one on mechanical therapy (eg, enhanced external counterpulsation). Findings suggested that interventions, although varied in duration and follow-up, were effective in improving mental health (SMD: 0.64, 95%, p<0.0497). There were also non-statistical improvements in fatigue (SMD: 1.74, 95%, p = 0.1307), quality of life (SMD: -1.34, 95%, p = 0.2787), and cognitive function (SMD: 1.05, p = 0.2989).<br><br>CONCLUSION: This review's findings suggest that non-pharmacological interventions may effectively treat neuropsychiatric symptoms of long COVID in AYA, ensuring better outcomes. Nevertheless, further research must be conducted with longer-term follow-up and robust methodology to explore sustained benefits, which may better inform treatment decisions.<br><br>TRIAL REGISTRATION: This systematic review is registered in Prospero (CRD42024516016).},
}
@article {pmid41878409,
year = {2026},
author = {Nübel, J and Beyer, AK and Kümpel, L and Eckert, G and Yessimova, D and Heldt, K and Mikolajewska, A and Sarganas, G},
title = {Long COVID in adults - a current review of the long-term health effects following SARS-CoV-2 infection.},
journal = {Journal of health monitoring},
volume = {11},
number = {},
pages = {02},
pmid = {41878409},
issn = {2511-2708},
abstract = {BACKGROUND: Long-term health effects associated with SARS-CoV-2 pose major challenges for public health and health research worldwide.<br><br>METHODS: Based on an ongoing literature review, a narrative review (as of June 2025) on the epidemiology and public health implications of long COVID in adults was compiled.<br><br>RESULTS: According to population-based, controlled studies, long COVID symptoms occur with a frequency of approximately 10 to 15 % in adults infected with SARS-CoV-2. In addition to COVID-19 vaccination status and virus variant, the risk of experiencing long COVID symptoms is primarily influenced by pre-existing health conditions and sociodemographic factors. In most affected individuals, long COVID symptoms resolve within a year. Particularly multiple and prolonged symptoms can be associated with significant impairments in quality of life, everyday functioning and social participation, as well as an increased need for healthcare. In addition, there is growing evidence of an infection-associated increase in newly diagnosed symptom complexes, organ damage and chronic diseases, contributing to the ongoing public health relevance of long COVID.<br><br>CONCLUSIONS: Long COVID is not only a major burden for those affected and their families, but also has unpredictable long-term consequences for public health and the healthcare system.},
}
@article {pmid41878417,
year = {2026},
author = {Ribeiro, A and Wallraven, T and Lech, M and Adorjan, K and Stubbe, HC and Seifert, M and Wöhnl, A and Kesseler, V and Negele, J and Schmaderer, C},
title = {SARS-CoV-2 spike S1-mediated HIF-2α activation in retinal endothelial cells suggests a mechanism contributing to post-COVID endothelial dysfunction.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1770758},
pmid = {41878417},
issn = {1664-3224},
mesh = {Humans ; *Endothelial Cells/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism/immunology ; *COVID-19/complications/immunology/metabolism ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; *Basic Helix-Loop-Helix Proteins/metabolism ; Aged ; *Retina/pathology/metabolism ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; Adult ; Cells, Cultured ; },
abstract = {BACKGROUND: Post-COVID-19 syndrome (PCS) is characterized by persistent symptoms such as fatigue, cardiovascular abnormalities, and cognitive impairment. Endothelial dysfunction (ED) has been proposed as a contributing factor, but underlying mechanisms remain unclear. We investigated whether SARS-CoV-2 spike protein subunit 1 (S1) is sufficient to induce ED in human retinal endothelial cells (HRECs) in vitro and whether pharmacologic inhibition of HIF-2α signaling modulates endothelial barrier integrity.<br><br>METHODS: In this study, we characterized 41 PCS patients and 24 pre-pandemic healthy controls. The effects of recombinant S1 and plasma from patients with severe PCS on endothelial function were assessed in HRECs. Belzutifan was used as a pharmacologic probe to assess the role of HIF-2&#x3b1; signaling in S1- and plasma-associated endothelial responses.<br><br>RESULTS: PCS patients exhibited elevated erythropoietin, VEGF, and MCP-1 levels compared with controls. VEGF correlated with anti-S1 IgG and was upregulated at the mRNA level in S1-exposed HRECs. Additionally, in vitro exposure to S1 induced ROS production, transient HIF-1&#x3b1; and sustained HIF-2&#x3b1; activation, VEGFR2 upregulation, and impaired endothelial barrier integrity. Plasma from patients with severe PCS increased ROS production and induced modest alterations in endothelial barrier function in HRECs. In both S1- and PCS-plasma-treated cells, pharmacologic HIF-2&#x3b1; inhibition with belzutifan improved endothelial barrier integrity.<br><br>CONCLUSION: These findings identify a spike-responsive, HIF-2&#x3b1;-associated ED pathway in retinal endothelial cells. Modulation of this pathway altered endothelial barrier responses to both recombinant S1 and plasma from patients with PCS, highlighting a candidate mechanism that may contribute to PCS-associated vascular dysfunction.},
}
@article {pmid41878441,
year = {2026},
author = {Ray, U and Schulze Selting, A and Perera, RP and Yang, Z and Lysenkov, V and Göpel, S and Bitzer, M and Salker, MS and Ossowski, S and Riess, O and Casadei, N and Singh, Y},
title = {Dysregulated NK-cell gene expression defines the enduring symptoms of long COVID-19.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1720551},
pmid = {41878441},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/genetics ; *Killer Cells, Natural/immunology/metabolism ; *SARS-CoV-2/immunology ; Male ; Female ; Middle Aged ; Adult ; Cytokines/blood ; Antibodies, Viral/blood ; Aged ; Gene Expression Profiling ; Transcriptome ; },
abstract = {INTRODUCTION: Long-term COVID-19 syndrome (LTCS) or "long COVID" is a debilitating post-viral condition affecting approximately 2%-8% of individuals after SARS-CoV-2 infection. It manifests typically ≥3 months post-infection with symptoms persisting for at least 2 months, including fatigue, pulmonary dysfunction, and cognitive impairment, in the absence of alternative diagnoses. The biological mechanisms underlying LTCS remain poorly defined, yet emerging evidence implicates immune dysregulation.<br><br>METHODS: We profiled plasma antibodies and cytokines from healthy controls (HC, N = 66), convalescents (CONV, N = 24), and LTCS patients (N = 94), followed by multiparametric 14-color flow cytometry of PBMCs from HC (N = 9), CONV (N = 6), and LTCS (N = 23) participants. To gain mechanistic insight, we performed single-cell transcriptomic profiling (scRNA-seq) on PBMCs from HC (N = 8), CONV (N = 6), and LTCS (N = 32) individuals.<br><br>RESULTS: LTCS patients exhibited elevated anti-SARS-CoV-2 IgG (spike S1/RBD/N) titers compared with HC, but displayed significantly reduced systemic cytokine levels, including IFN-&#x3b3;, TNF-&#x3b1;, IL-6, and IL-10. Flow cytometry revealed marked depletion of CD56[+]CD16[+] NK cells and CD56[+]CD3[+] NKT cells, accompanied by altered T-cell activation states. scRNA-seq confirmed NK type I cell loss and uncovered broad transcriptional reprogramming with upregulation of PDCD4, CHD1, CXCR4, and SLC7A5 and downregulation of TGFBR3, RIPOR2, and MBNL1. Gene set enrichment analyses indicated activation of circadian and translational programs and suppression of olfactory receptor, neurotransmitter receptor, and GABA-gated ion-channel pathways. Functional assays validated reduced NK-cell inflammatory capacity in LTCS participants.<br><br>DISCUSSION: LTCS is characterized by systemic cytokine attenuation and a quantitative and functional NK-cell deficit coupled to neurosensory pathway suppression. These findings identify NK cells as key sentinels of LTCS pathophysiology and highlight an NK-centric neuroimmune axis as a promising target for biomarker discovery and therapeutic intervention.},
}
@article {pmid41880292,
year = {2026},
author = {Sun, X and Cappelleri, JC and Lupton, LL and Moran, MM and Lopez, SMC and Puzniak, L and Yehoshua, A and Di Fusco, M},
title = {Assessment of long COVID symptom burden in patients testing positive for SARS-CoV-2 at a nationwide retail pharmacy.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0345639},
doi = {10.1371/journal.pone.0345639},
pmid = {41880292},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/diagnosis/epidemiology/virology ; Female ; Male ; Middle Aged ; Adult ; Patient Reported Outcome Measures ; SARS-CoV-2/isolation &amp; purification ; Fatigue ; Surveys and Questionnaires ; Pharmacies ; Aged ; Cost of Illness ; Quality of Life ; Symptom Burden ; },
abstract = {BACKGROUND: Numerous grouping and scoring methodologies have been proposed to assess long COVID symptomatology. One approach is to use symptom count as a simple, quantifiable measure of long COVID symptom burden.<br><br>METHODS: This was a secondary analysis of a nationwide patient-reported outcomes (PRO) study that recruited symptomatic adults testing positive for SARS-CoV-2 at a Retail Pharmacy in the spring of 2023. EQ-5D-5LTM, work productivity and impairment (WPAI), the Patient-Reported Outcomes Measurement Information System (PROMIS&#xae;) fatigue, and a long COVID symptom questionnaire were administered at Week 4, Month 3, and Month 6 after testing. Pre-infection EQ-5D-5L, WPAI, PROMIS fatigue were collected via recall. Cronbach's &#x3b1; assessed internal consistency of symptoms. Scree plots determined number of significant factors (symptoms) to retain for analysis. Spearman correlation coefficients were calculated between number of symptoms and EQ-5D-5L, WPAI, PROMIS fatigue scores and their changes from pre-COVID baseline. Categorization of long COVID burden using number of symptoms was proposed based on scores via equipercentile linking.<br><br>RESULTS: Of 505 patients, mean age was 46.3 years, 70.7% were female. Cronbach's &#x3b1; was 0.865, denoting good internal consistency of the symptom survey instrument. The scree plot supported use of one factor for the composite 30-symptom list. Number of symptoms correlated strongly with EuroQol Utility Index (r&#x2009;=&#x2009;-0.53), presenteeism (r&#x2009;=&#x2009;0.51), activity impairment (r&#x2009;=&#x2009;0.51) and fatigue (r&#x2009;=&#x2009;0.56). Statistically significant differences in mean number of symptoms were found between patients with versus those without problems in any of the 5 domains of the EQ-5-dimensional descriptive system. Based on linked PRO scores, subjects could be classified into low (&#x2264;2), medium (3-9), and high (&#x2265;10) symptom burden.<br><br>CONCLUSIONS: Number of long COVID symptoms correlated with validated PRO measures and identified three symptom-based categories of long COVID burden. Number of symptoms is a valid and internally consistent measure to assess long COVID burden in outpatient settings.},
}
@article {pmid41880397,
year = {2026},
author = {Reis, GGD and Moreira, DA and Parente, TE and Müller, BLA and Moreira, AS and Alves, G and Chantre-Justino, M and Delmonico, L and Lopes, BA and Silvestre, RT and Ornellas, MH and Santos, LSD and Mattos-Guaraldi, AL},
title = {MicroRNA sequencing of peripheral blood mononuclear cells reveals significant expression changes in women with Long COVID.},
journal = {Anais da Academia Brasileira de Ciencias},
volume = {98},
number = {1},
pages = {e20250515},
doi = {10.1590/0001-3765202620250515},
pmid = {41880397},
issn = {1678-2690},
mesh = {Humans ; Female ; *COVID-19/genetics/blood ; *MicroRNAs/genetics/blood ; *Leukocytes, Mononuclear/metabolism ; Middle Aged ; SARS-CoV-2/genetics ; Adult ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA ; },
abstract = {Long COVID is a clinical condition marked by persistent symptoms like fatigue and brain fog, estimated to have affected many of post-SARS-CoV-2/COVID-19 infection patients. This study, conducted with adult female Long COVID patients from Pedro Ernesto University Hospital (HUPE) in Rio de Janeiro, investigated the role of microRNAs (miRNAs), key post-transcriptional gene expression regulators, in this new condition. Next-generation sequencing (NGS) and bioinformatics analysis of miRNAs extracted from Peripheral Blood Mononuclear Cells (PBMCs) revealed differential expression of 37 miRNAs (10 upregulated, 27 downregulated). Notably, 28 of these miRNAs have been previously linked to inflammation or COVID-19, a significant finding given Long COVID's association with a persistent inflammatory state and potential for serious adverse events. Validation by qPCR confirmed hsa-miR-1307-3p, hsa-miR-26a-5p, and miR-186-5p as potential Long COVID biomarkers. The continuous overexpression of hsa-miR-1307-3p, which bound to the initial SARS-CoV-2 variants, may have contributed to increased inflammatory factors. Understanding how miRNAs modulate the inflammatory cascade could be crucial in mitigating the global health impact of future pandemics.},
}
@article {pmid41880671,
year = {2026},
author = {Garriga-Salvó, C and Navarro, E and Lidón-Moyano, C and Arévalo, A and Roca, R and Morera, M and Llistosella, M},
title = {Psychological interventions for individuals with long COVID: a systematic review and meta-analysis.},
journal = {Health psychology review},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/17437199.2026.2646179},
pmid = {41880671},
issn = {1743-7202},
abstract = {Introduction: Long COVID involves a variety of persistent symptoms after initial SARS-CoV-2 infection, affects multiple functional areas and requires multidisciplinary treatment. Objective: This study aimed to explore the available evidence about psychological interventions for individuals with long COVID and their effectiveness in reducing some prevalent symptoms, such as fatigue, anxiety or depression, among others, and improving patient quality of life. Methodology: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines. Two independent reviewers performed study selection and data extraction using Web of Science, Scopus, and PubMed databases prior to March 2024. Data synthesis was performed via random-effects meta-analysis, with heterogeneity assessed using the I2 statistic. Results: Of the 1041 articles obtained, 19 were included in the systematic review and 14 in the meta-analysis. Results showed significant reductions in symptoms of anxiety [SMD = -0.64 (95% CI: -1.18 to -0.10)], depression [SMD = -0.41 (95% CI: -0.73 to -0.10)] and fatigue [SMD = -1.37 (95% CI: -2.48 to -0.26)]. Significant improvements were only registered in self-perceived health-related quality of life [SMD = 7.59 (95% CI: 3.70-11.48)]. Conclusion: Results showed improvements in anxiety, depression or fatigue, highlighting the potential role of psychological interventions in patient recovery.},
}
@article {pmid41881023,
year = {2026},
author = {Chen, HJ and Appelman, B and Willemen, HLDM and Bos, A and Prado, J and Mak, WA and Keijzer, N and Santos Ribeiro, PS and Goncalves, SV and Versteeg, S and Geyer, CE and Larsen, M and Schüchner, E and Bomers, MK and Lavell, AHA and , and Charlton, B and Wüst, R and Wiersinga, WJ and van Vugt, M and Vidarsson, G and Eijkelkamp, N and den Dunnen, J},
title = {Transfer of IgG from long COVID patients induces symptomology in mice.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102693},
doi = {10.1016/j.xcrm.2026.102693},
pmid = {41881023},
issn = {2666-3791},
abstract = {SARS-CoV-2 infections have led to a surge in long COVID, a post-infectious syndrome in which autoantibodies are proposed to play a pathogenic role, analogous to fibromyalgia. Here, we test this hypothesis by transferring total IgG from long COVID patients into mice. We stratified patients into three subgroups using plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and interferon-β, with subgroup-specific pathways supported by plasma proteomics. Transfer of pooled total IgG induces pronounced and persistent mechanical hypersensitivity. Notably, IgG collected 2 years later from the same long COVID patients who remained symptomatic reproduced mechanical allodynia in mice, demonstrating longitudinal stability of pathogenic activity. Proteome-wide autoantibody profiling identifies elevated, subgroup-linked autoreactivities that persist over time and are validated by independent assays. Together, these findings demonstrate that long COVID IgG can induce mechanical hypersensitivity in mice, support a causal role for autoantibodies in long COVID pathogenesis, and may establish a murine model for therapeutic development.},
}
@article {pmid41873548,
year = {2026},
author = {Joseph, R and Rabelo, L and Do Nascimento, EB},
title = {Evidence of impaired processing speed and cognitive control in recovered COVID-19 patients: The role of cognitive slowing in long COVID memory impairment.},
journal = {Applied neuropsychology. Adult},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/23279095.2026.2649334},
pmid = {41873548},
issn = {2327-9109},
abstract = {Cognitive impairment is among the most reported symptoms in post-acute sequelae of SARS-CoV-2 infection. These impairments, often termed "brain fog" include difficulties in memory, attention, executive function, and processing speed, significantly impacting individuals' quality of life and daily functioning. This study investigates the hypothesis that survivors may exhibit impaired processing speed (PS) and cognitive control (CC), crucial components of cognitive functioning that potentially underlie learning and memory disturbances. An observational study was conducted with 61 participants (mean age: 35.7 ± 8.7 years, 53% female, 47% male), categorized into three groups: control (CTL), COVID symptomatic (COV-S), and hospitalized (COV-H). Participants were recruited through a sociodemographic and screening questionnaire and assessed using various cognitive and psychological evaluation tools, including the Five-Digit Test (FDT) and Rey Auditory Verbal Learning Test (RAVLT). Results indicate that declines in processing speed and cognitive control are related to the clinical condition of COVID-19, with greater severity observed in hospitalized individuals. The study provides robust evidence that COVID-19 affects processing speed and cognitive control, directly leading to slowed learning stages and impairments in the RAVLT encoding stage, due to increased interference during memory formation, affecting episodic-semantic memory tasks.},
}
@article {pmid41873998,
year = {2026},
author = {Goh, GK and Foster, JA and Uversky, VN},
title = {Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins.},
journal = {Advances in respiratory medicine},
volume = {94},
number = {2},
pages = {},
doi = {10.3390/arm94020018},
pmid = {41873998},
issn = {2543-6031},
mesh = {Humans ; *COVID-19/virology ; *SARS-CoV-2/pathogenicity ; Virulence ; Animals ; },
abstract = {Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2-but not in SARS-CoV-1-as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein-protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.},
}
@article {pmid41875425,
year = {2026},
author = {Lerma-Irureta, D and Méndez-López, F and Navarro-Matías, E and Lerma-Puertas, D and Magallón-Botaya, R},
title = {Differential Factors Associated With the Presence of Persistent Symptoms in Individuals Diagnosed With Long COVID: Protocol for a Longitudinal Matched Case-Control Study.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e67133},
doi = {10.2196/67133},
pmid = {41875425},
issn = {1929-0748},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology/diagnosis ; Case-Control Studies ; Longitudinal Studies ; Spain/epidemiology ; Quality of Life ; SARS-CoV-2 ; Adult ; Female ; Male ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Research Design ; },
abstract = {BACKGROUND: Long COVID (postacute sequelae of SARS-CoV-2 infection) is a heterogeneous condition with persistent multisystem symptoms and substantial functional burden. Integrative longitudinal studies combining clinical phenotyping, lifestyle factors, and immunobiological markers are needed to clarify determinants of symptom persistence and inform risk stratification and targeted interventions.<br><br>OBJECTIVE: This study aims to identify clinical, biological/immunological, and sociodemographic factors associated with Long COVID status by comparing individuals with persistent symptoms to matched recovered controls, and to evaluate longitudinal changes in symptoms and secondary outcomes over follow-up.<br><br>METHODS: ARALongCOV is a longitudinal matched case-control observational study conducted in Arag&#xf3;n, Spain, including adults (&#x2265;18 years of age) with confirmed SARS-CoV-2 infection. Participants are recruited through 3 sources: the Long COVID Arag&#xf3;n Patient Association, the Arag&#xf3;n Health Service database, and primary care consultations. Long COVID and recovered participants are individually matched 1:1 (without replacement) on sex/gender (exact), age (&#xb1;3 years), and date of acute COVID-19 diagnosis (&#xb1;30 days). Outcomes include persistent symptoms and functioning and patient-reported outcomes (quality of life, physical activity, diet, sleep, mental health, functional status, cognitive performance, pain catastrophizing, and fatigue), alongside clinical variables and biochemical/immunological markers (including inflammatory and cytokine profiles, SARS-CoV-2 antispike immunoglobulin G serology, and viral reactivation serologies). Measurements are obtained at baseline (T0) and repeated at follow-up (T1) using standardized procedures.<br><br>RESULTS: The study received ethics approval from the Clinical Research Ethics Committee of Arag&#xf3;n (PI21/278). Funding was provided by Instituto de Salud Carlos III through project PI22/01070 (cofunded by the European Union) for the period 2023-2027. Baseline assessments (T0) were initiated in late 2022/early 2023. As of February 2026, a total of 200 participants have been enrolled (n=100 Long COVID; n=100 recovered controls) and have completed T0; T1 assessments are scheduled for late 2025/early 2026 (~3-year follow-up for the earliest enrolled participants). Primary analyses will be conducted after completion of T1 assessments, with dissemination planned from the second half of 2026 and continuing through 2027.<br><br>CONCLUSIONS: This protocol describes a comprehensive, multidimensional longitudinal study designed to clarify determinants of Long COVID by integrating clinical, functional, lifestyle, and immunobiological data in matched cohorts. Findings are expected to support risk stratification, phenotype discovery, and identification of prognostic markers to inform preventive, diagnostic, and rehabilitative strategies.<br><br>TRIAL REGISTRATION: ISRCTN Registry ISRCTN27312680; https://tinyurl.com/33cbysrk.<br><br>DERR1-10.2196/67133.},
}
@article {pmid41875623,
year = {2026},
author = {Vianna, CM and de Figueiredo, AM and Camacho, LAB and Marques, CMC and Xavier, JR and da Gama, VC and Pizzini, GLC and Braga, RM and Santos, EAPD and Maia, MLS},
title = {Risk factors for post-COVID-19 condition: A case-control study in municipalities of Paraíba and Rio de Janeiro, Brazil.},
journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases},
volume = {30},
number = {2},
pages = {105807},
doi = {10.1016/j.bjid.2026.105807},
pmid = {41875623},
issn = {1678-4391},
abstract = {INTRODUCTION: Post-COVID-19 condition, refers to one or multiple symptoms that continue for several weeks or months following the COVID-19 infection. This study aims to assess the factors associated with post-COVID-19 condition in the Brazilians regions of Paraiba and Rio de Janeiro. Understanding this factor is crucial to public policies and improving care for high-risk individuals.<br><br>METHODS: This is a multicenter, retrospective case-control study. Cases were classified as individuals experiencing persistent symptoms for over 12-weeks following a confirmed COVID-19 diagnosis, whereas controls were those who recovered. Data on sociodemographic characteristics, medical history, lifestyle factors, and vaccination status were gathered, and logistic regression was used to analyze the relationship between these variables and the onset of post-COVID-19 condition.<br><br>RESULTS: Of the 1.350 participants, 734 were cases and 616 were controls, with a 54% frequency of post-COVID-19 condition. The study found significant associations between the syndrome and female sex (OR = 2.09; 95% CI 1.6&#x2012;2.74), middle age (OR = 2.03; 95% CI 1.31&#x2012;3.15 for 40- to 60-years) and over 60 (OR=1.84; 95% CI 1.06&#x2012;3.2), white people (OR = 1.41; 95% CI 1.07&#x2012;1.86), hypercholesterolemia (OR = 1.66; 95% CI 1.18&#x2012;2.32), chronic lung diseases (OR = 5.60; 95% CI 1.18&#x2012;26.65), mental illness such as anxiety and panic disorder (OR = 2.52; 95% CI 1.64&#x2012;3.87), family history of long COVID syndrome (OR = 2.07; 95% CI 1.45&#x2012;2.97), hospitalization (OR = 5.89; 95% CI 3.92&#x2012;8.86) and good pre-COVID health perception (OR = 0.69; 95% CI 0.53&#x2012;0.9).<br><br>CONCLUSIONS: The findings reinforce the importance of identifying groups more frequently affected by post-COVID-19 condition and supporting follow-up strategies aimed at mitigating its impact on individuals and health services.},
}
@article {pmid41876107,
year = {2026},
author = {Brierley, M and Vakilian, F and Rostami, M},
title = {When High Scores Hide Realities: Enhancing Patient Survey Data Through Joint Display.},
journal = {Annals of family medicine},
volume = {24},
number = {2},
pages = {153-158},
doi = {10.1370/afm.250474},
pmid = {41876107},
issn = {1544-1717},
mesh = {Humans ; *Patient Satisfaction/statistics &amp; numerical data ; Alberta ; *COVID-19/epidemiology ; Surveys and Questionnaires ; Qualitative Research ; SARS-CoV-2 ; Female ; *Health Care Surveys/methods ; },
abstract = {PURPOSE: Patient surveys often include closed- and open-ended responses that are usually reported separately, and links between them rarely explored, limiting interpretive depth. We outline a strategy that integrates quantitative and qualitative survey data in a joint display which enables combined analysis and findings to inform and improve programs for patients.<br><br>METHODS: Data were drawn from a patient experience survey implemented in Alberta's long COVID Inter-professional Outpatient Program (IPOP). A joint display of Likert-scale satisfaction ratings and themed open-text feedback was developed to examine connections between the structured responses and qualitative insights.<br><br>RESULTS: We integrated quantitative survey satisfaction ratings with themes from the qualitative analysis of open-text comments in a joint display. Examining these data sets together added an analytical layer and uncovered nuanced experiences not evident in Likert-scale responses alone. By aligning satisfaction scores with themes, the joint display surfaced contradictory and paradoxical findings that would otherwise be hidden.<br><br>CONCLUSIONS: Aligning Likert-scale responses with thematic analysis of open-text reveals subtleties that may be obscured by scores alone. Understanding the narratives behind ratings is essential to evaluate health care programming, particularly when surveys are the primary mechanism for incorporating patient voices into service planning and delivery.},
}
@article {pmid41869098,
year = {2026},
author = {Becker, KN and Hagood, M and Creeden, JF and Heck, H and Haak, PT and Larder, C and Tipton, C and Schroeder, J and Eisenmann, KM},
title = {Baseline Clinician Attitudes and Practices Regarding Long-Term Neurological Follow-Up for COVID-19 Patients: Early Pandemic Insights With Contemporary Relevance.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e103837},
pmid = {41869098},
issn = {2168-8184},
abstract = {OBJECTIVES: This study aimed to investigate clinician opinions and practices regarding long-term neurological follow-up for COVID-19 patients during the early pandemic period (June-August 2020), before formal long COVID recognition, and identify the gaps between clinician awareness and clinical practice implementation.<br><br>METHODS: &#xa0;We conducted a cross-sectional survey of 199 physicians and advanced practice providers (APPs; including nurse practitioners, physician assistants, certified registered nurse anesthetists (CRNAs), and similar roles) across Northwest Ohio and Southeast Michigan healthcare systems (June-August 2020). The survey assessed clinician awareness of long-term neurological risks, screening behaviors, referral practices, and attitudes toward long-term neurological follow-up using an original adaptive questionnaire administered via Qualtrics. Bivariate associations were tested using Pearson's chi-square and Fisher's exact test (p &#x2264; 0.05). This study was approved by the University of Toledo Institutional Review Board (Protocol #300681, exempt status).<br><br>RESULTS: &#xa0;Most respondents (54/96, 56.3%) believed that more than 50% of COVID-19 patients should receive long-term neurological follow-up, primarily by neurology specialists (66/134, 49.3%). However, only 13/93 (14.0%) were actively referring more than 50% of their COVID-19 patients for such care. Average referral rates increased modestly from 14.1% pre-pandemic to 19.9% during the pandemic, with 100/130 (76.9%) reporting no change in practices. Self-reported familiarity with neurological manifestations of COVID-19 (114/179, 63.7%) was substantially lower than general COVID-19 familiarity (178/180, 98.9%).<br><br>CONCLUSIONS: &#xa0;Substantial disconnect existed between clinician beliefs about appropriate care and actual referral practices, revealing infrastructure barriers, including inadequate specialty capacity and lack of standardized protocols. These baseline findings document the state of clinical practice before formal long COVID guidelines were established.<br><br>POLICY IMPLICATIONS: &#xa0;Healthcare systems require enhanced infrastructure for long-term neurological monitoring of COVID-19 survivors, including increased specialty capacity and standardized protocols, informing pandemic preparedness for chronic disease complications.},
}
@article {pmid41870866,
year = {2026},
author = {di Filippo, L and Terenzi, U and Bolamperti, S and Bechini, C and Bossoni, S and Campaniolo, M and Gifuni, L and Doga, M and Giustina, A},
title = {Chronic cholecalciferol supplementation and adequate vitamin D status are associated with reduced risk of Long COVID.},
journal = {Journal of endocrinological investigation},
volume = {},
number = {},
pages = {},
pmid = {41870866},
issn = {1720-8386},
support = {ABIONC06//ABIOGEN SPA/ ; },
}
@article {pmid41870982,
year = {2026},
author = {Fernández, GA and Baratta, MSG and Klajn, DS},
title = {Long COVID in children and adolescents: Incidence and clinical characteristics in Buenos Aires, 2021-2023.},
journal = {Archivos argentinos de pediatria},
volume = {},
number = {},
pages = {e202510958},
doi = {10.5546/aap.2025-10958.eng},
pmid = {41870982},
issn = {1668-3501},
abstract = {Introduction. Long COVID affects approximately 8.5% of the pediatric and adolescent population after SARS-CoV-2 infection, and vaccination could reduce its incidence. Objectives. To determine the incidence of long COVID in children and adolescents aged 5 to 18 years, describe symptoms and duration, analyze differences by age and sex, estimate reinfections and school absenteeism, and evaluate its relationship with vaccination. Population and methods. Prospective cohort study conducted between August 1, 2021, and February 1, 2023. To calculate incidence, patients with COVID-19 treated at a general acute care hospital in the Autonomous City of Buenos Aires were included; for characterization, cases referred from other centers were included as well. Descriptive and comparative analyses were performed, estimating incidence with 95% CI; STATA 14.0 was used (p <0.05). The study was approved by the Ethics Committee. Results. Of 496 patients, 475 were included, and 21 were excluded due to severe comorbidities. The incidence of long COVID was 7.79% (95% CI 5.37-10.21). Those affected had a higher mean age (12.57 vs. 11.20 years; p = 0.02) and a higher incidence in unvaccinated or partially vaccinated individuals (11.48% vs. 5.48%; p = 0.018). The most common symptoms were fatigue, cough, and myalgia. Conclusion. The incidence of long COVID was comparable to that reported in other pediatric series. A lower incidence was observed in children and adolescents with complete vaccination schedules, and fatigue was the most frequent clinical manifestation. These findings reinforce the need to continue generating evidence.},
}
@article {pmid41864480,
year = {2026},
author = {Rauf, M and Naveed, A and Asghar, MU},
title = {Post-acute sequelae of COVID-19: A disorder of impaired innate immune resolution - A narrative review.},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {285},
number = {},
pages = {110701},
doi = {10.1016/j.clim.2026.110701},
pmid = {41864480},
issn = {1521-7035},
abstract = {Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC.},
}
@article {pmid41862909,
year = {2026},
author = {Khalid, K and Abdullah, ADI and Lim, HX and Ali, RAR},
title = {Pharmacological and non-pharmacological management of long COVID.},
journal = {Virology journal},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12985-025-02991-5},
pmid = {41862909},
issn = {1743-422X},
abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health burden in terms of acute infection and long-term consequences. Approximately 10% of infected experience autonomic dysfunction, cardiovascular complications, and neurological impairments. While immune dysregulation, persistent viral reservoirs, chronic inflammation, gut dysbiosis, and vascular dysfunction are implicated, the exact pathophysiological mechanisms of Long COVID remain unclear. Additionally, treatment options are limited and challenging to prescribe due to symptom heterogeneity. Non-pharmacological interventions such as increased salt intake, elimination diets for gastrointestinal symptoms, and cognitive pacing for fatigue may not be sufficient for severe symptoms. Moreover, pharmacological interventions such as β-blockers, calcium channel blockers, pyridostigmine, antihistamines, and low-dose naltrexone can improve tachycardia, fatigue, and brain fog but there are no standardized guidelines. In light of evidence supporting a strong association of Long COVID with gut dysbiosis, probiotics have emerged as a promising intervention. Clinical studies have shown that Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium species can improve fatigue, gastrointestinal health, and overall physical and mental well-being in Long COVID patients. Large-scale randomized controlled trials are warranted to validate probiotic efficacy in Long COVID and reduce burden on individual health and healthcare institutions.},
}
@article {pmid41862917,
year = {2026},
author = {Luo, S and Zheng, Z and Karimi, L and Plebanski, M and Lankatillake, C and Sheahan, J and Anderson, K and Jovanovski, N and Seal, EL and Cockshaw, W and Wollersheim, D and Cleary, S and El-Ansary, D and Flanagan, KL and Jessup, R and Abrahamson, S and Whyler, N and Fineberg, D and Scoullar, MJL and Seeley, MC and Tippett, E and Xenos, S and Itsiopoulos, C},
title = {Between silence and solutions: a global guideline review of long COVID care and services in Australia.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14268-w},
pmid = {41862917},
issn = {1472-6963},
}
@article {pmid41857005,
year = {2026},
author = {Gandhi, MM and Moser, C and Currier, JS and Ritz, J and Eron, JJ and Daar, ES and Wohl, DA and Fischer, WA and Singh, U and Hughes, MD and Smith, DM and Evering, TH and Chew, KW and , },
title = {Association of long COVID with health-related quality-of-life outcomes.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36189-8},
pmid = {41857005},
issn = {2045-2322},
support = {UM1AI068634//National Institute of Allergy and Infectious Diseases/ ; UM1AI068636//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher's exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45-6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.},
}
@article {pmid41857445,
year = {2026},
author = {Friedberg, A and McConnell, E and Stanwick, S and Perez, L and MacEwan, S and Rush, LJ and Bowman-Burpee, S and Smith, RM and Joshi, S and Woschkolup, K and Grandominico, J and McAlearney, AS and Schamess, A},
title = {Outcomes of Patients with Neurocognitive Symptoms Attending a Long COVID Clinic: A Longitudinal Cohort Study.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41857445},
issn = {1525-1497},
abstract = {BACKGROUND: Data are lacking on longitudinal outcomes of patients treated in primary care-led long COVID (LC) clinics.<br><br>OBJECTIVE: Assess changes in health-related quality of life (HRQoL) in patients with LC and neurocognitive symptoms from enrollment in a LC clinic to 6&#xa0;months post-enrollment.<br><br>DESIGN: Observational cohort study.<br><br>SETTING: Primary care-led LC clinic at an academic medical center.<br><br>PARTICIPANTS: One hundred fifty patients with long COVID and neurocognitive symptoms who completed the PROMIS29 inventory at clinic enrollment and 6&#xa0;months post-enrollment.<br><br>INTERVENTIONS: Multimodality care consisting of disease education and behavioral management, rehabilitative therapies, and pharmacotherapy for LC symptoms.<br><br>MAIN MEASURES: Treatments received and change in PROMIS29 t-scores from enrollment to 6-month follow-up.<br><br>KEY RESULTS: T-scores (mean, SE) at clinic entry were worse than the population mean (50) for fatigue (65.6, 1.05), sleep disturbance (57.3, 1.00), anxiety (60.0, 1.26), physical function (37.9, 0.87), social role participation (40.2, 0.84), pain (60.1, 1.24), and depression (57.3, 1.11). Patients received multimodality treatment consisting of disease education and behavioral management (all patients), combined rehabilitation and pharmacotherapy (44%), rehabilitation only (22%), or pharmacotherapy only (16%). There were statistically significant improvements in mean t-scores in all PROMIS29 domains at 6&#xa0;months. Clinically significant improvement (change in t-score of&#x2009;&#x2265;&#x2009;2.5) was seen for physical functioning (+&#x2009;2.9, 0.58), fatigue (-&#x2009;4.9, 0.80), social functioning (+&#x2009;3.4, 0.68), and pain (-&#x2009;2.8, 0.88). Change in t-score&#x2009;>&#x2009;5 was seen in fatigue with symptom-titrated physical rehabilitation, in fatigue and pain with amantadine and memantine, and in sleep disturbance and pain with trazodone and amitriptyline.<br><br>CONCLUSION: Multimodal symptom-directed interventions incorporating rehabilitation alongside targeted pharmacotherapy were associated with significantly improved HRQoL in patients with LC and neurological symptoms.},
}
@article {pmid41859298,
year = {2026},
author = {Blitshteyn, S and Doherty, TA and Steinman, L},
title = {Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.},
journal = {ImmunoTargets and therapy},
volume = {15},
number = {},
pages = {581262},
pmid = {41859298},
issn = {2253-1556},
abstract = {Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.},
}
@article {pmid41860011,
year = {2026},
author = {Houchen-Wolloff, L and Bell, J and Pritchard, R and Poinasamy, K and Holmes, K and Walker, S and Smith, N and Hastie, C and Rogers, N and Adams, D and Nathu, R and Gill, R and Bunker, J and Staunton, L and Chalmers, J and Ho, LP and Harris, V and Horsley, A and Marks, M and Raman, B and Wain, LV and Brightling, C and Evans, R},
title = {Consortium-Based Patient and Public Involvement and Engagement for Long COVID Research: A Pirit-Focused Impact Evaluation of the PHOSP-COVID Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70591},
doi = {10.1111/hex.70591},
pmid = {41860011},
issn = {1369-7625},
support = {+ MRC: MR/V027859/1//National Institute for Health and Care Research/ ; COV0319//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; *Patient Participation ; *Community Participation ; SARS-CoV-2 ; *Survivors ; Pandemics ; },
abstract = {BACKGROUND: At the start of the coronavirus disease-2019 (COVID-19) pandemic in early 2020, the long-term outcomes for survivors of COVID-19 were unknown. The PHOSP-COVID cohort study was set up at scale and pace in Spring 2020 to determine the short- to long-term health consequences of COVID-19 in post-hospitalisation survivors; to understand the impact of interventions during and after the acute illness on these long-term sequelae and to build the foundation for multiple in-depth studies. A consortium infrastructure of hospital trusts, academic partners, industry, patients and charities was created. From the study inception, patients were central to the PHOSP-COVID consortium, whereby a Patient and Public involvement and Engagement (PPIE) group was convened, including charity groups, people with lived experience recruited through clinical care from NHS sites, and patient support groups through Long Covid Support. Embedding high-quality, meaningful PPIE within a large consortium brings challenges and benefits. In this article, we describe our experiences of setting up and sustaining the PHOSP-COVID Consortium PPIE group, including a PIRIT-focussed evaluation of the impact of our PPIE work and provide top tips for researchers to take forward when embedding PPIE in future consortium research.<br><br>METHODS: This article outlines the set-up and sustainability of the PHOSP-COVID study PPIE group, in consultation with the National Institute for Health and Care Research (NIHR) guidance. To evaluate PPIE impact, we used PIRIT (Public Involvement in Research Impact Tool, 2023- Cardiff), and we provide our honest reflections of our PPIE work according to the PIRIT planning tool. The results highlight the benefits of a consortium approach to PPIE as well as the challenges, with quotes from PPIE contributors and academics. In addition, we have created top tips for researchers to take forward when embedding PPIE in future consortium research, linked to the NIHR standards.<br><br>LEARNING AND REFLECTION: This manuscript has identified gaps in PPIE considerations for the PHOSP-COVID study and specific challenges around a consortium-based approach for PPIE. These are largely due to time scale (i.e. the pace of setting up the study within a pandemic) and communication factors (diverse and large numbers of people to include/inform). Through reflection on the challenges and successes experienced in the PHOSP-COVID consortium PPIE via a PIRIT-focused impact evaluation, we have developed recommendations to support future good practice.<br><br>Patients and members of the public were involved in all aspects of this work from idea inception, design and conduct of the work, analysis and interpretation of the data. Eight patients prepared the manuscript and are included as co-authors.},
}
@article {pmid41860534,
year = {2026},
author = {Anderer, S},
title = {Long COVID Prevalence Decreases as Recovery Rates Improve.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.1021},
pmid = {41860534},
issn = {1538-3598},
}
@article {pmid41861144,
year = {2026},
author = {Oehlke, SM and Goreis, A and Lozar, A and Klinger, D and Plener, PL and Zeiler, M and Kothgassner, OD},
title = {Understanding the role of psychological factors in long COVID: a network analysis approach.},
journal = {European journal of public health},
volume = {36},
number = {2},
pages = {},
doi = {10.1093/eurpub/ckag038},
pmid = {41861144},
issn = {1464-360X},
support = {//European Economic and Social Committee (EWSA)-Fund/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; Female ; Male ; Adult ; Middle Aged ; Anxiety/epidemiology/psychology ; Depression/epidemiology/psychology ; Self Efficacy ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Aged ; },
abstract = {Long COVID (LC) is a heterogeneous, multisystem condition that persists beyond the acute phase of SARS-CoV-2 infection. Psychological symptoms are highly prevalent and may influence the course and severity of LC. However, their specific role within the broader symptom structure remains insufficiently understood. This study applied a psychological network approach to examine how psychological factors contribute to the overall symptom structure of LC and to identify central and bridging variables that may serve as promising targets for intervention. A sample of 283 individuals with LC (nfemale = 235, nmale = 47, ndiverse = 1; age: M = 39.48, SD = 13.29) completed an online survey assessing post-viral physical symptoms and psychological factors, including depression, anxiety, COVID-19-related traumatic stress, and lack of self-efficacy. A regularized partial correlation network was estimated based on ten variables. The network revealed a dense degree of connectivity, with psychological factors integrated into the broader symptom structure. Depression emerged as the most central variable. Cardiovascular and respiratory symptoms, neurological symptoms, and depression served as key bridge variables. Lack of self-efficacy showed moderate associations with COVID-19-related traumatic stress and anxiety. Female gender was linked to greater gastrointestinal symptom burden, while older age was associated with more pronounced cardiovascular and respiratory symptoms. This study underscores the central role of psychological factors-particularly depression-as key targets for intervention in LC. By advancing the understanding of factors shaping health outcomes in LC, our findings support the integration of psychological approaches into the clinical management of affected individuals.},
}
@article {pmid41861186,
year = {2026},
author = {Kawamura, T and Kohno, J and Kikuchi, A and Arita, R and Takayama, S and Ishii, T},
title = {Factors involved in the improvement of prolonged symptoms in patients with COVID-19 treated with Japanese traditional (Kampo) medicine: A single-center, prospective, observational study.},
journal = {Medicine},
volume = {105},
number = {12},
pages = {e48084},
doi = {10.1097/MD.0000000000048084},
pmid = {41861186},
issn = {1536-5964},
support = {none//Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine/ ; },
mesh = {Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; *Medicine, Kampo/methods ; Fatigue/etiology ; *COVID-19/complications/therapy ; Aged ; Japan/epidemiology ; *COVID-19 Drug Treatment ; Adult ; SARS-CoV-2 ; Treatment Outcome ; *Drugs, Chinese Herbal/therapeutic use ; East Asian People ; },
abstract = {Patients with prolonged symptoms of COVID-19 (PSC) show various symptoms, especially fatigue, which affect their activities of daily living and inhibit their return to social life. As there is no standard treatment for PSC, we developed a treatment regimen that includes Japanese traditional (Kampo) medicine according to patient symptoms and condition. This study aimed to investigate the progression of symptoms in patients with PSC using this treatment regimen and to assess differences in background factors that affect the improvement of symptoms in patients. We conducted a prospective, observational study and collected data from patients with PSC who visited a hospital in Japan between May 2022 and December 2023. The patient performance status (PS, 0-9) and 16 symptoms on a numerical rating scale (NRS, 0-10) were recorded at each visit. A total of 114 patients were analyzed. The group with a first visit general fatigue score equal to or greater than the median (GMGF group) took more time to achieve PS ≤ 2 (hazard ratio [95% confidence interval (CI)], 0.405 [0.253-0.650], P < .001) and the end of visit milestone (0.283 [0.150-0.532], P < .001) compared to the group with a first visit general fatigue score less than the median (LMGF group). The group with ≥90 days from the onset to the first visit (≥90 days group) reached the end of visit milestone significantly later (0.510 [0.267-0.974], P = .041) than the group with <90 days from the onset (the <90 days group). The odds ratios (95% CI) for achieving PS ≤ 2 and the end of visit milestone within 3 months of the first visit in the GMGF group were 0.140 (0.046-0.425, P < .001) and 0.148 (0.058-0.380, P < .001), respectively. The ≥90 days group experienced difficulty in achieving the end of visit milestone within 3 months of the first visit (odds ratio [95% CI], 0.430 [0.179-1.035], P = .06). Patients with PSC who have a high general fatigue score at their first visit may have difficulty improving their symptoms. Early treatment, including Kampo medicine, can promote the improvement of PSC symptoms.},
}
@article {pmid41851212,
year = {2026},
author = {Kukreti, S and Yeh, CY and Lu, MT and Imteyaz, K and Strong, C and Ko, NY},
title = {Post-acute sequelae of SARS-CoV-2 infection symptom network centrality analysis of Taiwan population to unveil intricate symptomatology patterns.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-41991-5},
pmid = {41851212},
issn = {2045-2322},
support = {114-2811-B-006-028//National Science and Technology Council/ ; },
}
@article {pmid41851917,
year = {2026},
author = {Allen, AJ and Ward, M},
title = {Long COVID should be a public health concern.},
journal = {Perspectives in public health},
volume = {},
number = {},
pages = {17579139261429368},
doi = {10.1177/17579139261429368},
pmid = {41851917},
issn = {1757-9147},
}
@article {pmid41852583,
year = {2026},
author = {Ramer, V and van Montfrans, GA},
title = {Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.},
journal = {Biochemistry and biophysics reports},
volume = {46},
number = {},
pages = {102518},
pmid = {41852583},
issn = {2405-5808},
abstract = {An explanation for long COVID (LC) and its many symptoms remains elusive, and no unifying upstream mediator of its pathophysiology has yet been identified. Viral infections, including COVID-19, upregulate Prostaglandin E2 (PGE2), - the principal lipid mediator of inflammation. PGE2 has broad paracrine effects, including modulation of autoantibodies, nervous systems, blood pressure, glucose levels, and apoptosis. Upregulated, PGE2 may drive multiple pathological processes through its four receptors: EP1-EP4. Through EP3, PGE2 stimulates characteristic viral sickness symptoms. Both severe and mild disease may precede LC, possibly reflecting either excessive or insufficient EP3 activity, which we term "EP3 up" and "EP3 down", respectively. In individuals with "EP3 up" or "EP3 down" states, elevated PGE2 levels may disrupt homeostasis. Diverse physical and mental stressors upregulate PGE2. Data suggest that multiple hormones and agents stimulate PGE2 production, while PGE2 reportedly antagonizes these agents, possibly functioning as a homeostatic limiter. Sufficiently elevated PGE2, "PGE2 dominance", may interfere with their activity through inhibiting their release, overlapping subcellular signaling pathways or by stimulating phosphorylation and autoantibodies. Homeostatic elevations of PGE2-stimulating hormones, together with other PGE2-raising factors, may promote resistance to these hormones, resulting in persistent PGE2 upregulation. Literature suggests that PGE2 overactivity, mediated by imbalanced EP receptor signaling, aligns with the diverse symptomatology of LC. Based on our literature analysis, we propose that persistent upregulation of PGE2 plays a pivotal role in the development of LC. Consequently, validation of elements of this framework may help guide exploration of therapeutic strategies targeting PGE2 pathways or EP receptor regulation.},
}
@article {pmid41852926,
year = {2026},
author = {Gutzeit, J and Weiß, M and Bahmer, T and Lieb, W and Schreiber, S and Vehreschild, JJ and Nürnberger, C and Pütz, SM and Heim, E and Ruß, AK and Dempfle, A and Krawczak, M and Poick, S and Schäfer, A and Morbach, C and Lehmann, C and Polidori, MC and Reese, JP and Zoller, T and Krist, L and Heyckendorf, J and Reinke, LM and Deckert, J and Hein, G and , },
title = {Long-term trends in Post-COVID severity: a machine learning analysis from the POP/COVIDOM cohort of the German NAPKON Cohort Network.},
journal = {EClinicalMedicine},
volume = {93},
number = {},
pages = {103822},
pmid = {41852926},
issn = {2589-5370},
abstract = {BACKGROUND: Post-COVID syndrome (PCS) affects many survivors with varying symptom profiles driven by acute disease severity (PCS-S) or individual resilience (PCS-R). While cross-sectional studies have identified risk factors and gender differences, long-term trajectories remain unclear. This study investigates the stability and progression of PCS-S and PCS-R scores after 9, 24 and 36 months from initial diagnosis, identifying key predictive factors stratified by gender.<br><br>METHODS: We analyzed data from 1526 participants of the German National Pandemic Cohort Network (NAPKON), modeling symptom-based PCS-score trajectories over time with linear mixed-effects models. Data were split into training (n = 944), test (n = 233), and two-site external validation (n = 349) sets. Gender-stratified elastic-net regression used nine-month clinical and psychosocial measures to predict PCS scores at 24 and 36 months. All data were collected between November 2020 and February 2024. The study is registered on ClinicalTrials.gov (NCT04679584) and in the German Registry for Clinical Studies (DRKS00023742).<br><br>FINDINGS: PCS-S and PCS-R scores showed small but significant declines between 9 and 36 months (&#x3b2; = -0.054 and -0.065, respectively; p < 0.001), indicating persistent symptom burden despite gradual improvement. Predictive models explained 16.7-52.6% of variance in later PCS severity. Fatigue after 9 months and age predicted later PCS-S; quality of life and depression added predictive value in females. Fatigue and sleep issues predicted PCS-R, with living/employment status relevant in females and cognitive deficits in males.<br><br>INTERPRETATION: The severity of PCS subtype manifest after 9 months remains relatively stable over time, with distinct gender-specific predictors shaping symptom progression. Tailored interventions are essential for long-term management of PCS pathways.<br><br>FUNDING: The COVIDOM study is funded by the Network University Medicine as part of the NAPKON.},
}
@article {pmid41855420,
year = {2026},
author = {Deng, J and Tao, L and Liu, N and Li, J and Qin, C and Yan, W and Wang, Y and Du, M and Liu, Q and Liu, J},
title = {Rehabilitation status and preference for medical choice behaviours of long COVID-19 in China: a national cross-sectional study and discrete choice experiment.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04081},
doi = {10.7189/jogh.16.04081},
pmid = {41855420},
issn = {2047-2986},
mesh = {Humans ; Cross-Sectional Studies ; *COVID-19/rehabilitation/epidemiology/psychology ; Male ; Female ; China/epidemiology ; Middle Aged ; Adult ; *Choice Behavior ; *Patient Preference/statistics &amp; numerical data ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Health Status ; },
abstract = {BACKGROUND: Long COVID-19 has emerged as a growing global public health challenge requiring patient-centred responses, yet its prevalence and management are often underestimated. We aimed to investigate the rehabilitation status and medical choice behaviours among patients with long COVID-19 in China during the Omicron wave.<br><br>METHODS: We conducted a national cross-sectional study and a discrete choice experiment (DCE) in China from 4 July to 11 August 2023. We used the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) to assess rehabilitation status. We collected preferences for medical choice behaviours of long COVID-19, demographics, health-related factors, and COVID-19 history. We assessed preferences for medical choice behaviours among people with long COVID-19 using mixed logit models.<br><br>RESULTS: Among 2942 participants health status was significantly poorer than before COVID-19 infection. The prevalence of common symptoms assessed by C19-YRSm ranged from 21.52% to 72.67%, with fatigue (72.67%) being the most common, followed by breathlessness on walking up a flight of stairs (64.96%) and sleep problems (62.95%). Of these symptoms, the majority of participants (15.06-47.65%) reported mild problems. Of the five functional limitations, difficulty with other activities of daily living (31.03%) was the most common, followed by difficulty with communication (28.04%), while difficulty with personal care (9.65%) was the least common. The DCE results showed that the strongest attribute affecting preferences was medical distance (&#x3b2;&#x2009;=&#x2009;-1.135). While seeking healthcare for long COVID-19, people preferred lower out-of-pocket costs, a closer distance, a higher hospital level, nutritional supportive therapies or rehabilitation training, and medical services that integrate traditional Chinese and Western medicine.<br><br>CONCLUSIONS: A substantial proportion of individuals developed long COVID-19 symptoms and functional limitations, most of which were mild. These findings highlight the importance of ongoing screening and comprehensive, tailored rehabilitation services to promote recovery and avert a public health crisis of long COVID-19.},
}
@article {pmid41856437,
year = {2026},
author = {Perez-Mazzali, M and Pérez-Cózar, F and Cal-Sabater, P and Rybakowska, P and Tellería, P and Gamazo, J and De Vicuña, MG and Arribas-Rodríguez, E and Fiz-López, A and de Castro, CG and García-Blesa, A and Rello, SR and De Prado, &#xc1; and Pérez, C and Tamayo, E and Orduña, A and Dueñas, C and Marañón, C and Bernardo, D and Cuesta-Sancho, S},
title = {Persistent T cell phenotypic alterations and early innate immune dysregulation as potential biomarkers of Long COVID.},
journal = {The Journal of infection},
volume = {},
number = {},
pages = {106731},
doi = {10.1016/j.jinf.2026.106731},
pmid = {41856437},
issn = {1532-2742},
abstract = {Long COVID is a complex condition characterized by a broad spectrum of persistent, multisystemic symptoms that often impair daily activities and cause disability with significant socioeconomic impact. Although several hypotheses have been proposed to explain its pathophysiology-including immune dysregulation-the underlying mechanisms remain poorly understood. Indeed, there are no current treatments for this condition. Therefore, we aimed to characterize immune alterations induced by SARS-CoV-2 during the acute phase of infection and three months post-hospital discharge in a cohort of patients who later developed Long COVID, referred to a matched cohort who did not. We performed high-dimensional immune profiling of peripheral blood mononuclear cells using a 40-marker mass cytometry panel. Data analysis combined classical hierarchical gating strategies with unsupervised computational approaches. Our results revealed distinct immune signatures between Long COVID and non-Long COVID patients, affecting both the innate and adaptive immune compartments. Notably, individuals who subsequently developed Long COVID exhibited early abnormalities at infection in innate immunity, particularly involving dendritic cells and γδ T cells. Moreover, three months post-discharge, persistent alterations were observed in several adaptive immune cell subsets in patients who next developed Long COVID over time. In summary, our findings suggest that early immune dysregulation following viral infection may predispose individuals to persistent post-viral pathology.},
}
@article {pmid41856465,
year = {2026},
author = {Malakooti, SK and Abboud, M and Murphy, JE and Singer, NG and McComsey, GA},
title = {Autoimmune Disease is Associated with Heightened Long COVID Risk but Prior Immunization is Protective.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108540},
doi = {10.1016/j.ijid.2026.108540},
pmid = {41856465},
issn = {1878-3511},
abstract = {OBJECTIVES: Patients with autoimmune disease (AD) may be predisposed to Long COVID, yet the impact of primary autoantibody-associated AD and prior immunization remains unclear.<br><br>METHODS: TriNetX, a global electronic health database, identified adults with confirmed SARS-CoV-2 infection between January 1, 2020 and September 21, 2023 and at least one follow-up visit >90 days later. Long COVID was defined as persistent or new symptoms &#x2265;90 days after infection. Patients with and without pre-existing AD were propensity-score-matched on demographics and comorbidities. Logistic regression assessed odds of Long COVID, with additional sensitivity analyses performed.<br><br>RESULTS: Among 2,472,196 patients with SARS-CoV-2, 289,206 had AD (+AD). After matching, baseline characteristics were similar. +AD patients had higher odds of all Long COVID symptoms compared with -AD patients. The highest odds were observed for disturbance to smell/taste (OR:1.99;95%CI:1.88-2.11), hair loss (OR:1.96;95%CI:1.89-2.04), abnormal movements/tremors (OR:1.93;95%CI:1.88-1.98), and body aches (OR:1.85;95%CI:1.81-1.89). Unvaccinated +AD patients had higher odds of all symptoms compared with matched unvaccinated -AD. Within +AD, primary autoantibody-associated AD demonstrated higher odds of most symptoms.<br><br>CONCLUSION: Pre-existing AD increases the risk of Long COVID, with the highest risk in primary autoantibody-associated AD. Prior vaccination mitigates the risk of most Long COVID symptoms in +AD patients, with heightened protection observed in primary autoantibody-associated AD.},
}
@article {pmid41856572,
year = {2026},
author = {Cao, B and Soriano, JB and Wang, Q and Al-Aly, Z and Gu, X and Wang, G and Leo, YS and Jin, Y and Shi, Q and Ohmagari, N and Liu, E and Paredes, R and Lu, H and Kim, ES and Zhang, D and Estill, J and Li, L and Spruyt, K and Yang, W and Wang, Y and Ran, M and Luo, X and Zhang, H and Xu, J and Zhang, R and Zhao, J and Zhao, J and Evans, RA and Jeon, J and Peluso, MJ and Errett, LE and Zhang, W and Chalmers, JD and Chen, Y and , },
title = {Clinical practice guideline for long COVID prevention and treatment.},
journal = {The European respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1183/13993003.02611-2025},
pmid = {41856572},
issn = {1399-3003},
abstract = {BACKGROUND: This guideline aims to address key clinical questions of long COVID, and to provide evidence-base recommendations. The target population is adults with long COVID. The primary users of the guideline are clinical physicians, clinical pharmacists, nurses, and general practitioners in community healthcare institutions worldwide.<br><br>METHODS: The guideline was registered at the Practice guideline REgistration for transPAREncy platform (PREPARE-2024CN123) and followed a pre-specified protocol. A multidisciplinary working group was established and comprised 60 members from 10 countries and 10 area of expertise, with a strong background in long COVID research and clinical practice, and methodology of guideline development. Through a two-step process, we determined the 8 PICO questions focusing on prevention and treatment of long COVID. After comprehensively searching literature, conducting systematic reviews, and investigating patients' values and preferences, three rounds of Delphi survey were conducted among 24 international experts to reach consensus. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to rate the certainty of evidence and determine the strength of recommendations.<br><br>RESULTS: The guideline presents 10 specific recommendations, each supported by existing, updated, or newly conducted systematic reviews. The key recommendations are pertinent to the following issues: 1) suggestion of vaccination or use of antiviral agents during the acute phase of COVID-19 to prevent long COVID; 2) suggestions against the use of nirmatrelvir-ritonavir and glucocorticoids (patients with persistent respiratory symptoms and olfactory disorders) for long COVID treatment; 3) suggestions supporting the use of multi-species probiotics, cognitive behavioral therapy (patients with fatigue), and personalized rehabilitation after excluding post-exertional malaise for long COVID treatment.<br><br>CONCLUSIONS: This guideline provides evidence-based recommendations for the prevention and treatment of long COVID. Given the limited and often low-methodological quality evidence, all recommendations are supported by very low to moderate certainty. Further high-quality studies are needed to strengthen the evidence base.},
}
@article {pmid41845161,
year = {2026},
author = {Saurer, P and Ballouz, T and Cusini, A and Haile, SR and Kahlert, CR and von Kietzell, M and Kuster, SP and Rütti, M and Schlegel, M and Strahm, C and Stocker, R and Vuichard-Gysin, D and Risch, L and Puhan, MA and Dörr, T and Kohler, P and , },
title = {Persistence of Post-Acute COVID-19 Sequelae (PASC) symptoms in healthcare workers four years after ancestral SARS-CoV-2 infection: a prospective multicentre cohort.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {41845161},
issn = {1439-0973},
support = {31CA30_196544//Swiss National Sciences Foundation SNSF/ ; },
abstract = {PURPOSE: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID (LC), remains a significant burden for public health, with limited long-term data. This study aimed to assess the prevalence and evolution of PASC symptoms after ancestral SARS-CoV-2 (aSCV2) infection in a longitudinal healthcare worker (HCW) cohort.<br><br>METHODS: A multicentre cohort study involving HCWs from 14 institutions was conducted in Switzerland. Infection status was based on self-reported positive swabs, with additional serology used to confirm uninfected controls. Baseline was defined as the first survey conducted in 2022 (median 18.5&#xa0;months post-infection), with follow-up surveys every 6&#xa0;months through November 2024. To identify PASC-specific symptoms, 24 chronic symptoms were compared between 456 aSCV2-infected and 571 uninfected participants using chi-square tests at baseline. In aSCV2-infected individuals reporting PASC-specific symptoms, symptom trajectories and subjective LC were analyzed across follow-up surveys. Functional limitations were assessed using the Post-COVID Functional Status (PCFS) scale.<br><br>RESULTS: Thirteen of 24 symptoms were more common in aSCV2-infected individuals, with fatigue (22.8%), loss of smell/taste (11.4%), and brain fog (8.3%) being most prevalent. At baseline, 186/456 (40.8%) infected participants reported&#x2009;&#x2265;&#x2009;1 PASC-specific symptom. Most symptoms declined in prevalence up to the last survey (median 47.5&#xa0;months post-infection), although 41/70 (58.6%) remaining participants still reported&#x2009;&#x2265;&#x2009;1 PASC symptom. Subjective LC was reported by 70/186 (37.6%) and was associated with higher symptom burden. PCFS scores showed slight impairments in most cases, although moderate-to-severe limitations often persisted.<br><br>CONCLUSIONS: PASC symptoms persisted up to four years after aSCV2 infection in a substantial proportion of HCWs.},
}
@article {pmid41847505,
year = {2026},
author = {Chagay, N and Tamadon, A and Kim, S and Dossimov, A and Issanguzhina, Z and Tulegenova, G and Kuldeeva, G and Puxovikova, N and Kim, I and Mussin, NM and Sharoffidin, RS},
title = {Pediatric-related post-COVID condition (long COVID) research and its foundational influences: a bibliometric analysis (2020-2025).},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1677983},
pmid = {41847505},
issn = {2296-2360},
abstract = {BACKGROUND: The COVID-19 pandemic significantly influenced healthcare systems worldwide. The long-term consequences of the infection in children, the phenomenon of post-COVID-19 syndrome, have been attracting increasing attention of the scientific community. The present study is a bibliometric analysis of publications addressing post-COVID (long COVID) complications in pediatric population over the period 2020-2025.<br><br>METHODS AND MATERIALS: The analysis covers 1,292 records retrieved from Scopus and Web of Science (search date: June 2025). Records were retrieved using post-COVID condition/long COVID terminology combined with pediatric-related keywords; therefore, the corpus includes pediatric-focused studies as well as influential general PCC publications indexed with pediatric terms and frequently cited in pediatric research. The search strategy combined post-COVID condition/long COVID terminology with pediatric terms (child/infant/adolescent), applying filters for English language, publication years 2020-2025, and document type (articles and reviews). Data were merged and analyzed in R using bibliometrix/Biblioshiny to describe productivity, collaboration, citations, and thematic structure.<br><br>RESULTS: The retrieved corpus included 1,292 publications from 84 countries/regions. The United States led productivity with 270 publications (20.9%), followed by the United Kingdom (114; 8.8%) and China (90; 7.0%). The most frequent author keywords included "COVID-19" (n&#x2009;=&#x2009;900) and "long COVID" (n&#x2009;=&#x2009;818). Highly cited items predominantly consisted of general or mixed-age PCC frameworks, indicating that foundational long COVID literature substantially shapes citation patterns within pediatric-tagged publications. Thematic mapping showed symptom-focused clusters as dominant, while MIS-C and cognitive impairment were less prominent in author-keyword frequency and thematic clustering within the retrieved dataset.<br><br>CONCLUSION: The findings describe the pediatric-term-indexed PCC research landscape and highlight substantial gaps in pediatric-specific evidence, definitions, and longitudinal data.},
}
@article {pmid41848128,
year = {2025},
author = {Hajji, H and Kalai, A and Chaabeni, A and Migaou, H and Jebali, B and Ben Salah Frih, Z and Ben Saad, H and Jellad, A},
title = {Beyond the basics: exploring non-conventional treatment for fatigue in post-acute COVID-19 syndrome.},
journal = {La Tunisie medicale},
volume = {103},
number = {9},
pages = {1265-1271},
doi = {10.62438/tunismed.v103i9.5926},
pmid = {41848128},
issn = {2724-7031},
mesh = {Humans ; *COVID-19/complications/therapy ; Post-Acute COVID-19 Syndrome ; *Fatigue/therapy/etiology ; SARS-CoV-2 ; Dietary Supplements ; Acupuncture Therapy/methods ; },
abstract = {INTRODUCTION: Post-acute 2019 coronavirus disease syndrome (PACS) is a multifaceted, multisystem disorder affecting an estimated 75 million individuals globally (in May 2024). Defined by symptoms persisting beyond four weeks post-infection, PACS manifests in subacute (4-12 weeks) and chronic (>12 weeks) phases, with fatigue being a prominent and debilitating feature. Comprehensive management of PACS-associated fatigue needs diverse therapeutic strategies extending beyond conventional rehabilitation.<br><br>AIM: This narrative review explored non-conventional interventions for PACS-related fatigue, focusing on treatments involving nutritional rehabilitation, physical modalities, and other innovative therapies.<br><br>METHODS: Narrative review.<br><br>RESULTS: Treatments reported in the literature include melatonin, QingjinYiqi, nutritional supplements, aromatherapy, antioxidants, Tai Chi, acupuncture, yoga, singing, hyperbaric oxygen therapy (HBOT), pulsed electromagnetic field therapy, and whole-body vibration. Melatonin and QingjinYiqi have shown notable improvements in fatigue and overall health. Nutritional supplements such as vitamin-minerals combinations have demonstrated enhancements in muscle strength, physical performance, and quality of life. Tai Chi, acupuncture, and yoga have shown positive effects on fatigue, muscle strength, and overall well-being. Aromatherapy, singing, HBOT, pulsed electromagnetic field therapy, and whole-body vibration effectively reduce fatigue while enhancing physical and cognitive functions.<br><br>CONCLUSION: These non-conventional treatments offer promising supplementary benefits to conventional rehabilitation.},
}
@article {pmid41849004,
year = {2026},
author = {Gebetsroither, P and Ettenauer, T and Likar, R},
title = {Treatment of post-COVID symptoms with auricular vagus nerve stimulation.},
journal = {Wiener medizinische Wochenschrift (1946)},
volume = {},
number = {},
pages = {},
pmid = {41849004},
issn = {1563-258X},
abstract = {We present a retrospective analysis of nine long COVID patients undergoing auricular vagus nerve stimulation for 4 weeks. Questionnaires screening for 35 symptoms and 22 aspects of quality of life showed improvements in 28/35 symptoms immediately after treatment, of which 19 persisted at the 12-week follow-up. Most benefits were reported with regards to pain, fatigue, post-exertional malaise, sleep and dysautonomia. Furthermore, the vast majority (19 out of 22) of aspects of quality of life were reported to have improved to various degrees.},
}
@article {pmid41849271,
year = {2026},
author = {Pham, ANQ and Smith, J and Byers, KA and Card, KG},
title = {Associations between demographic, clinical, and socioeconomic factors and mental health in long COVID: A clinic-based cross-sectional study.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0342516},
doi = {10.1371/journal.pone.0342516},
pmid = {41849271},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; *COVID-19/psychology/epidemiology/complications ; Middle Aged ; Cross-Sectional Studies ; *Mental Health ; Adult ; Socioeconomic Factors ; *Anxiety/epidemiology ; *Depression/epidemiology ; British Columbia/epidemiology ; Aged ; SARS-CoV-2/isolation &amp; purification ; Chronic Disease ; },
abstract = {BACKGROUND: Long COVID is associated with persistent symptoms, including the onset of new mental health challenges such as anxiety and depression, as well as the worsening of pre-existing conditions. While previous research has examined the impact of demographic factors, chronic conditions, and traumatic events on mental health, little is known about how these factors interact to shape mental health outcomes in individuals with Long COVID. This study investigates the relationship between selected demographics characteristics, social determinants of health - specifically living settings, place of living, employment status, and working hours - and chronic health conditions on mental health outcomes among individuals with Long COVID.<br><br>METHODS: This is a secondary analysis using previously collected survey data from 3,611 individuals, who were diagnosed, referred to and admitted at Post-COVID Recovery Clinics, British Columbia, Canada at the time of their admission. The dataset includes demographic variables (sex, age, living situation, employment status, occupation, ethnicity), history of chronic conditions, and mental health outcomes (anxiety and depression) of patients. Univariable and multivariable Generalized Linear Regression analyses were conducted to examine associations between SDoH and mental health outcomes, adjusting for potential confounders.<br><br>RESULTS: The cohort had a mean age of 50 years, and 62% of participants were female. Overall, 38% screened positive for anxiety, 35% for depression, and 26% for both conditions following COVID-19 infection. In multivariable analyses, younger age, cognitive issues, and activity limitations were significantly associated with symptoms of anxiety, while younger age, cognitive issues, and physical impairments were significantly associated with symptoms of depression. In the multivariable model, individuals with cognitive issues were more likely to report anxiety (RR&#x2009;=&#x2009;1.45, 95% CI: 1.34-1.56) and depression (RR&#x2009;=&#x2009;1.54, 95% CI: 1.42-1.68). Activity limitations were also associated with anxiety (RR&#x2009;=&#x2009;1.12, 95% CI: 1.01-1.24), and physical impairments with depression (RR&#x2009;=&#x2009;1.43, 95% CI: 1.24-1.65). Overall, 38% of patients reported symptoms of anxiety, 35% reported depression, and 26% experienced both following COVID-19 infection.<br><br>CONCLUSION: These findings highlight important associations between mental health symptoms and clinical factors among individuals with Long COVID and underscore the need for further longitudinal research to clarify causal pathways and inform mental health support strategies, particularly among those with activity limitations, cognitive and physical impairments.<br><br>The data collection and questionnaire were designed and conducted by the Post-COVID Integrated Clinic Network in British Columbia, Canada.},
}
@article {pmid41850429,
year = {2026},
author = {Kraus, T and Napierala, H and Schrimpf, A and Joos, S and Blaschke, S and Hanses, F and Vehreschild, MJGT and Hamelmann, E and Schmidt, J and Scheer, CS and Römmele, C and Göpel, S and Almahfoud, M and Dahl, E and Hamprecht, A and Kaasch, AJ and Wendel, J and Ole Jensen, BE and Tepasse, PR and Dashti, H and Vehreschild, JJ and Scherer, M and Bröhl, I and Raquib, S and Nürnberger, C and Reese, JP and Appel, KS and Krefting, D and Förster, C and , },
title = {Impact of COVID-19 vaccination on post-COVID syndrome across clinical definitions and phenotypes: a prospective multicenter cohort study.},
journal = {Mayo Clinic proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mayocp.2026.02.018},
pmid = {41850429},
issn = {1942-5546},
abstract = {OBJECTIVES: To assess the impact of COVID-19 vaccination on distinct clinical definitions and phenotypes of post-COVID syndrome (PCS) and identify risk factors for PCS despite vaccination.<br><br>METHODS: Data were drawn from the German National Pandemic Cohort Network (NAPKON), including adult COVID-19 patients with known vaccination status recruited between December 2, 2020, and February 13, 2023. PCS prevalence was assessed using 3 clinical definitions: the broad WHO definition (any sequelae at 3 months), symptom clusters (Fatigue, Respiratory, Cognitive), and a symptom-based PCS score reflecting clinical severity. Multivariable logistic regression was employed to estimate the protective effect of vaccination.<br><br>RESULTS: Among 756 patients, 26% were fully vaccinated (&#x2265;2 doses) before infection. Vaccination was associated with a significantly reduced risk of PCS according to the WHO definition (OR 0.555, 95% CI 0.339-0.906), the PCS score (OR 0.536, 95% CI 0.335-0.856), the Respiratory Cluster (OR 0.508, 95% CI 0.295-0.875), and the Cognitive Cluster (OR 0.443, 95% CI 0.213-0.923). In contrast, no protective association was observed for the Fatigue Cluster (OR 0.917, 95% CI 0.554-1.519). The favorable association with vaccination was particularly observed in patients with mild acute symptoms, regardless of hospitalization. The protective effect of vaccination persisted at 12-month follow-up, although fatigue remained unaffected.<br><br>CONCLUSION: Findings indicate that broader PCS definitions may mask clinically relevant heterogeneity and support the need for differentiated, phenotype-oriented definitions that reflect clinical presentations of PCS, including differential responses to vaccination. Such refined clinical definitions may facilitate exploration of whether these phenotypes reflect distinct underlying pathophysiological mechanisms.},
}
@article {pmid41840045,
year = {2026},
author = {Boever, J and Jakob, A and Paetzold, C and Gomes, D and Birzele, LT and Baalmann, K and Haas, NA and Nussbaum, C},
title = {Microcirculatory impairment and increased arterial stiffness in pediatric Long COVID patients.},
journal = {European journal of pediatrics},
volume = {185},
number = {4},
pages = {},
pmid = {41840045},
issn = {1432-1076},
mesh = {Humans ; *Microcirculation/physiology ; Female ; *Vascular Stiffness/physiology ; *COVID-19/physiopathology/complications ; Male ; Child ; Adolescent ; SARS-CoV-2 ; Endothelium, Vascular/physiopathology ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; },
abstract = {PURPOSE: The exact pathogenesis of Long COVID remains unclear. Microvascular and endothelial dysfunction, established contributors to SARS-CoV-2-related conditions, appear to play a role in pediatric Long COVID.<br><br>METHODS: At the Children's University Hospital of LMU Munich, we conducted a comparative cohort study including pediatric Long COVID patients. Microcirculation was assessed using sublingual sidestream dark field (SDF) imaging, analyzing the microvascular flow index (MFI), the total vessel density (TVD), and the proportion of perfused vessels (PPV). Endothelial function and arterial stiffness were evaluated using peripheral arterial tonometry (EndoPAT), measuring reactive hyperemia index (RHI) and augmentation index (AIx@75).<br><br>RESULTS: We analyzed 37 pediatric Long COVID patients (13.5&#x2009;&#xb1;&#x2009;2.6&#xa0;years; 22 females) with persisting symptoms (>&#x2009;4&#xa0;weeks) and 46 healthy controls (12.4&#x2009;&#xb1;&#x2009;4.8&#xa0;years; 21 females). Patients exhibited significant microcirculatory alterations, with reduced MFI (2.59 [IQR, 2.38-2.75] vs. 2.83 [IQR, 2.69-2.96]; p&#x2009;=&#x2009;.003), TVD (16.12 [IQR, 15.24-17.86] mm/mm2 vs. 19.38 [IQR, 17.58-20.57] mm/mm2; p&#x2009;<&#x2009;.001), and PPV (13.58 [IQR, 12.72-14.89]% vs. 17.67 [IQR, 16.60-19.32]%; p&#x2009;<&#x2009;.001). Microcirculatory changes varied with clinical phenotype and were most pronounced in patients presenting with dyspnea.We analyzed 37 pediatric Long COVID patients (13.5&#x2009;&#xb1;&#x2009;2.6 years; 22 females) with persisting symptoms (>&#x2009;4 weeks) and 46 healthy controls (12.4&#x2009;&#xb1;&#x2009;4.8 years; 21 females). Patients exhibited significant microcirculatory alterations, with reduced MFI (2.59 [IQR, 2.38-2.75] vs. 2.83 [IQR, 2.69-2.96]; p&#x2009;=&#x2009;.003), TVD (16.12 [IQR, 15.24-17.86] mm/mm2 vs. 19.38 [IQR, 17.58-20.57] mm/mm2; p&#x2009;<&#x2009;.001), and PPV (13.58 [IQR, 12.72-14.89]% vs. 17.67 [IQR, 16.60-19.32]%; p&#x2009;<&#x2009;.001). Microcirculatory changes varied with clinical phenotype and were most pronounced in patients presenting with dyspnea.<br><br>CONCLUSION: We demonstrate measurable vascular alterations in pediatric Long COVID, including microvessel reduction and increased arterial stiffness. Our findings support a role of vascular changes in Long COVID and highlight the importance of integrating cardiovascular monitoring and follow-up into the management of affected children.<br><br>WHAT IS KNOWN: &#x2022; Microvascular and endothelial dysfunction appear to play a role in SARS-CoV-2-related diseases. &#x2022; Adults with Long COVID show persistent capillary rarefaction and endothelial impairment supporting a vascular mechanism underlying ongoing symptoms.<br><br>WHAT IS NEW: &#x2022; Pediatric Long COVID is likewise associated with significant microvascular damage and furthermore with increased arterial stiffness. &#x2022; Children with dyspnea exhibit a distinct vascular phenotype characterized by marked capillary loss, indicating a potential microvascular origin of persistent respiratory symptoms.},
}
@article {pmid41840047,
year = {2026},
author = {Bonnefoy, PB and Pascal, P and Ceyrat, Q and Burg, S and Razzouk-Cadet, M and Moreau Triby, C and Biancheri Mounicq, I and Bourre, JC and Salaun, PY and Le Roux, PY},
title = {Functional alterations due to post-COVID-19 lung lesions - lessons from a multicenter V/Q SPECT/CT based registry.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41840047},
issn = {1619-7089},
}
@article {pmid41840532,
year = {2026},
author = {He, S and Liu, Y and Li, Y and Ji, L and Liu, Y and Yan, J and Zhang, Z and Sun, H and Gao, M and Wu, S},
title = {Immune-inflammatory mediators of frailty and long COVID in older adults: a prospective cohort study.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07328-7},
pmid = {41840532},
issn = {1471-2318},
support = {LKZ2023007//Jiangsu Geriatric Health Research Project/ ; BE2023704//Project of Jiangsu Province Science and Technology Plan Special Fund/ ; },
}
@article {pmid41840550,
year = {2026},
author = {Schmidt, L and Feddern, S and Kossow, A and Niessen, J and Grüne, B and Schmidt, N and Haberstock, L and Rost, S and Joisten, C and , },
title = {Severe acute COVID-19 and early long COVID signals in paediatric cohorts: an analysis of real-world data from two health departments, Germany.},
journal = {BMC pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12887-026-06724-7},
pmid = {41840550},
issn = {1471-2431},
}
@article {pmid41841761,
year = {2026},
author = {Ward, B and Bindels, LB and Balligand, J-L and Bearzatto, B and Bommer, G and Cani, PD and De Greef, J and Dewulf, JP and Gatto, L and Haufroid, V and Jodogne, S and Kabamba, B and Pyr Dit Ruys, S and Vertommen, D and Yombi, JC and Belkhir, L and Elens, L},
title = {Association of nasopharyngeal Dolosigranulum pigrum and Corynebacterium species with post-acute sequelae of SARS-CoV-2 in a longitudinal cohort.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0231325},
doi = {10.1128/spectrum.02313-25},
pmid = {41841761},
issn = {2165-0497},
abstract = {This longitudinal study investigated the differential composition of the nasopharyngeal microbiome in patients presenting different COVID-19 infectious phenotypes and its evolution during convalescence, with a focus on post-acute sequelae of SARS-CoV-2 (PASC) and its potential microbiome-related mechanisms. Microbiota composition was assessed for a cohort of healthy participants (n = 25), influenza patients (n = 24), and patients with moderate (n = 50) and severe (n = 57) COVID-19. Samples were collected at two time points: during the acute infection phase and at approximately 3-month follow-up. From collected nasopharyngeal swab samples, metagenomics using shotgun sequencing was performed and the microbiota composition was analyzed. Alpha and beta diversity analyses revealed no significant differences in overall community diversity between patient groups across visits. However, differential abundance testing identified specific species, such as Dolosigranulum pigrum and various Corynebacterium species, whose profiles correlated with PASC development. Furthermore, the analysis of microbial co-associations identifies commensal species, including D. pigrum and Corynebacterium species, which are less abundant in patients who develop PASC, consistent with a potential protective role suggested by experimental studies but not proven by our observational data. Antibiotic use was associated with lower levels of key protective taxa, which may increase susceptibility to PASC in case of superinfection. These findings highlight the potential importance of the nasopharyngeal microbiome in acute COVID-19 disease outcomes and suggest that preserving or restoring a balanced respiratory microbiome could mitigate the risk of COVID-19 persistent symptoms and PASC development. Our results may set the stage for future clinical interventions involving probiotics or microbial-derived metabolites to promote respiratory health post-COVID-19.IMPORTANCEThis study highlights the importance of bacteria naturally found in the upper respiratory tract, particularly the nasopharynx (the nasopharyngeal microbiome), in shaping how severely COVID-19 affects patients and whether they experience persistent symptoms, also called long-COVID or post-acute sequelae of SARS-CoV-2 (PASC). By examining microbiome samples from healthy people, influenza patients, and individuals with COVID-19 during acute and convalescent phases, we found that certain commensal bacteria, namely, Dolosigranulum pigrum and Corynebacterium species, were less abundant in individuals who developed long-COVID and more abundant in those who fully recovered. We also observed that antibiotic treatment was associated with lower abundances of these commensal taxa, in turn coinciding with a higher frequency of PASC. These findings suggest that the composition of the nasopharyngeal microbiome is associated with recovery trajectories after COVID-19 and motivate future research into treatments aimed toward the microbiome to improve respiratory health following infection.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05557539.},
}
@article {pmid41835098,
year = {2026},
author = {Dos Santos, LPM and Leão, JV and Silva, KYBM and Dos Santos, DL and Batista, CN and Barros, JA and Paranhos, ACM and Dias, &#xc1;RN and Falcão, LFM},
title = {Transcranial stimulation as a possible therapeutic proposal in long COVID.},
journal = {Frontiers in rehabilitation sciences},
volume = {7},
number = {},
pages = {1766757},
pmid = {41835098},
issn = {2673-6861},
abstract = {The COVID-19 pandemic triggered an unprecedented global health crisis, with significant repercussions on the mental and neurological health of millions of individuals. Long COVID, characterized by persistent and debilitating symptoms, including chronic fatigue, pain, cognitive impairment, and mood swings, represents a substantial therapeutic challenge. In this context, neuromodulation emerges as a promising therapeutic strategy, offering new perspectives for the management of refractory neurological symptoms. This article aims to critically review the current evidence on the use of neuromodulation in patients with long COVID.},
}
@article {pmid41836412,
year = {2026},
author = {Korobova, ZR and Totolian, AA},
title = {Principal component analysis of cytokine signature in COVID-19 and Long COVID.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1717107},
doi = {10.3389/fimmu.2026.1717107},
pmid = {41836412},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/blood ; *Cytokines/blood/immunology ; *SARS-CoV-2/immunology ; Male ; Middle Aged ; Female ; Principal Component Analysis ; Adult ; Aged ; Biomarkers/blood ; },
abstract = {INTRODUCTION: Despite the activity of the COVID-19 pandemic being lower in the recent years, COVID-associated threat, long COVID (LC). Its clinical presentation includes nearly 200 symptoms affecting cardiovascular, respiratory, nervous systems, endocrine organs, urinary tract, and gastrointestinal systems. Cytokines serve as important biomarkers for assessing the level of immune system involvement and dysregulation in LC. Most studies on cytokine network and cytokine interactions usually address more traditional methods of statistical analysis with comparison criteria, discriminant analysis, regression. But multiplex cytokine analysis includes dozens of parameters, and requires complex assessment of the network as a whole.<br><br>METHODS: We analyzed data of cytokine multiplex analysis of 289 patients with COVID-19, 44 patients with LC and 51 healthy donors. PCA we identified cyotkines with the highest importance rate, and further investigated between them with the use of 3D mapping.<br><br>RESULTS: Three key clusters were identified: cluster A - IL-13, CCL7/MCP-3, IL-4; cluster B - IL-18, CCL2/MCP-1, CCL4/MIP-1&#x3b2;, CXCL8/IL-8, M-CSF, and cluster C - sCD40L, CXCL1/GRO&#x3b1;, PDGF-AA, EGF, FGF-2, FLT-3L, IL-7, IL-17F.<br><br>DISCUSSION: The coordinated interactions within these clusters reveal a complex immunopathology behind LC: clsuter A repsresenting local immune responses, cluster B for neuroinflammatory processes, and cluster C for changes in the blood vessels. The results, however, leave an opening for further investigatoin and interpretation.},
}
@article {pmid41836919,
year = {2026},
author = {Aguzin Parrilli, LJ and Belzunce, MA},
title = {Bias and generalizability of brain age prediction models: A multi-cohort evaluation with anatomical and interpretability insights.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
doi = {10.1162/IMAG.a.1164},
pmid = {41836919},
issn = {2837-6056},
abstract = {Brain age prediction from T1-weighted MRI and its associated brain age gap (BAG) has emerged as a promising neuroimaging biomarker for assessing deviations from normative aging. However, the robustness, bias, and interpretability of existing models across external datasets remain poorly understood, limiting clinical translation. In this study, we evaluated four publicly available brain age models (ENIGMA, DeepBrainNet, Pyment, and BrainAgeNeXt) across four independent MRI datasets (ADNI, UNSAM Long COVID, and two OpenNeuro cohorts), comprising 1,634 subjects with diverse demographic and clinical profiles. Models were tested using their original preprocessing pipelines, and performance was assessed using mean absolute error (MAE), mean error (ME), and BAG variability metrics, with additional analyses of biases related to age, dataset, ethnicity, and education. Interpretability was evaluated using Layer-wise Relevance Propagation, and anatomical correlates were explored using BrainChart-derived centile scores. Group-level comparisons were performed between cognitively normal (CN) individuals and patients with Mild Cognitive Impairment (MCI), Alzheimer's disease (AD), or Long COVID (LC). Models based on 3D convolutional neural networks (Pyment and BrainAgeNeXt) outperformed the DeepBrainNet 2D CNN and the ENIGMA ridge regression model in both accuracy (MAE: 3.9-3.7 vs. 6.2-12.4 years respectively) and stability (ASTD: 3.2-2.9 vs. 4.6-8.3 years). Dataset-specific BAG differences were largely explained by age distributions, whereas ethnicity showed a statistically significant but small effect on BAG in some models. Relevance maps highlighted the lateral ventricles as the most consistently relevant anatomical region, with additional cerebellar contributions emerging in older adults for BrainAgeNeXt. Group-level analyses confirmed elevated BAG in MCI and AD patients compared to CN, while no significant differences were observed in Long COVID participants. These findings suggest that, while BAG is a promising biomarker for group-level analyses, current models are required to address age and demographic biases to enable individual-level clinical application.},
}
@article {pmid41836927,
year = {2026},
author = {Baptista, SN and Atkins, T and Chakraborty, S and Bakhit, M and Glasziou, P and Byambasuren, O},
title = {Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1734600},
doi = {10.3389/fmed.2026.1734600},
pmid = {41836927},
issn = {2296-858X},
abstract = {OBJECTIVE: To map the existing evidence for candidate treatments for long COVID that were prioritised by clinicians and people with lived experience, and to characterise their feasibility, acceptability and safety.<br><br>STUDY DESIGN: The study was conducted as a narrative review using pragmatic methods including iterative stakeholder-informed decision-making a monthly-updated evidence search, rapid lay evidence summaries and a structured research prioritisation process.<br><br>DATA SOURCES: Potential candidate treatments were identified via a combination of database and trial registry searches. These were then ranked by clinicians and people with lived experience using surveys. Evidence summaries for the top 14 interventions (low-dose naltrexone, antivirals, metformin, nicotine, vagus nerve stimulation, antihistamines, guanfacine, colchicine, nattokinase, intravenous immunoglobulins, monoclonal antibodies, coenzyme Q10, multicomponent rehabilitation packages, and exercise training) were created. Prioritised treatments were collated first by searching a collaborative living evidence database (updated monthly) of relevant systematic reviews and randomised controlled trials and then by conducting supplementary searches of other study designs.<br><br>DATA SYNTHESIS: Six of 14 interventions had long-COVID-specific randomised controlled trial (RCT) evidence (exercise [16 RCTs], multicomponent packages [5 RCTs], coenzyme Q10 [2 RCTs], antivirals [1 RCT], vagus nerve stimulation [1 pilot RCT], monoclonal antibodies [1 small RCT]); the remainder relied on indirect or very low-certainty data (e.g., uncontrolled studies or mechanistic rationale). Across interventions, evidence certainty was mostly low to very low, and safety/feasibility varied.<br><br>CONCLUSION: This review prioritises and maps candidate treatments for long COVID. There was insufficient direct evidence to inform clinical recommendations. Rather, the treatments presented in this review represent those that could be rigorously tested in clinical trials as they show biological plausibility and/or are feasible and acceptable to people with lived experience and clinicians.<br><br>REGISTRATION: A review protocol was not prospectively registered because the review adopted an iterative approach to support priority setting rather than clinical guidance.},
}
@article {pmid41830160,
year = {2026},
author = {Cataldo, SA and Horovitz, SG and Margulis, L and Micciulli, A and Sarmiento, F and Monteleone, M and Brocco, M and Belzunce, MA},
title = {Spatial Coefficient of Variation (sCOV) From ASL MRI Reveals Global Cerebrovascular Dysfunction in Long COVID.},
journal = {NMR in biomedicine},
volume = {39},
number = {4},
pages = {e70264},
doi = {10.1002/nbm.70264},
pmid = {41830160},
issn = {1099-1492},
support = {IW-8320273708//International Brain Research Organization/ ; FITBA-B06//Ministerio de la Producci&#xf3;n, Ciencia y Tecnolog&#xed;a/ ; PICT-PRH-2022-01//Agencia Nacional de Promoci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/diagnostic imaging/complications ; Middle Aged ; *Magnetic Resonance Imaging/methods ; *Cerebrovascular Circulation ; Spin Labels ; *Cerebrovascular Disorders/diagnostic imaging/physiopathology ; Adult ; Aged ; Brain/diagnostic imaging/blood supply ; SARS-CoV-2 ; },
abstract = {Long COVID is increasingly associated with persistent neurological and cognitive symptoms, yet its underlying mechanisms remain unclear. Vascular dysregulation, endothelial dysfunction, and microvascular injury have been proposed as potential contributors. Arterial spin labeling (ASL) MRI allows noninvasive quantification of cerebral blood flow (CBF) and assessment of vascular function. Previous studies have reported hypoperfusion in long COVID patients, but few have accounted for delayed arterial transit time, which can affect ASL quantification. The spatial coefficient of variation (sCOV) has been previously used as a proxy of arterial transit time, providing a noninvasive marker of global cerebrovascular function. We examined 186 adults from an Argentine cohort (145 long COVID and 41 controls), approximately 2 years postinfection. Three-dimensional pulsed ASL data were processed with ExploreASL to quantify CBF and sCOV in gray matter and lobar regions. Group comparisons were performed using multivariate models adjusted for age, sex, and white matter hyperintensity (WMH) volume. Long COVID participants showed significantly higher global gray matter sCOV compared with controls (p = 0.02), with consistent regional trends across the frontal (L: p = 0.05; R: p = 0.07), temporal (L: p = 0.05; R: p = 0.08), parietal (L: p = 0.07; R: p = 0.06), occipital (L: p = 0.08; R: p = 0.05), and insular (L: p = 0.01; R: p = 0.15) lobes after FDR correction. Mean global, lobar, and regional gray matter CBF and WMH volumes did not differ significantly between groups. Increased sCOV, reflecting delayed arterial transit and reduced vascular efficiency, indicates widespread cerebrovascular dysfunction in the absence of perfusion deficits and not associated with white matter hyperintensities. These findings provide evidence of global vascular impairment in long COVID and support sCOV as a sensitive, noninvasive biomarker of cerebrovascular health.},
}
@article {pmid41828637,
year = {2026},
author = {Menário, CVB and Silva-Aguiar, RP and Teixeira, DE and Nascimento, GS and Visconti, NRGR and Andrade, LS and Mello, FCQ and Lapa-E-Silva, JR and Rocha, NN and Martins, CM and Cruz, FF and Pinheiro, AAS and Silva, PL and Rocco, PRM and Caruso-Neves, C},
title = {Tubular Damage Biomarkers Are a Useful Tool for Identifying Early Renal Injury in Long COVID.},
journal = {International journal of molecular sciences},
volume = {27},
number = {5},
pages = {},
doi = {10.3390/ijms27052420},
pmid = {41828637},
issn = {1422-0067},
support = {grants 465656/2014-5 (to P.M.R.R. and C.C.-N.), 306433/2022-2 and 444068/2024-4 (to A.A.S.P.), and 309112/2021-4 and 406836/2024-8 (to C.C.-N.)//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; grants E-26/210.181/2020 (to P.M.R.R. and C.C.-N.), E-26/203.926/2024 and E-26/210.046/2023 (to C.C.-N.), E-26/200.564/2023 (to A.A.S.P.), and E-26/210.824/2021 (to all authors)//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro (FAPERJ)/ ; Finance Code 001 and CAPES/PRINT 88887.508141/2020-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior (CAPES)/ ; },
mesh = {Humans ; *COVID-19/complications ; Male ; Female ; *Biomarkers/urine ; Middle Aged ; Glomerular Filtration Rate ; Cross-Sectional Studies ; Aged ; *Acute Kidney Injury/diagnosis/etiology ; Albuminuria ; *Kidney Tubules/pathology/metabolism ; SARS-CoV-2 ; Adult ; },
abstract = {Patients without overt glomerular dysfunction may develop tubular injury, referred to as subclinical acute kidney injury. The burden of COVID-19-related renal damage may therefore be underestimated, as current KDIGO criteria do not include tubular damage biomarkers (TDBs). This study evaluated kidney injury in patients with long COVID by assessing TDBs alongside glomerular biomarkers, proteinuria (UPCr) and albuminuria (UACr). In this cross-sectional study, 75 patients without prior chronic kidney disease were recruited from a long COVID outpatient clinic and stratified according to the time since SARS-CoV-2 infection into 6-, 12-, and 24-month post-COVID-19 groups (referred to as 6-, 12-, and 24-MPC, respectively). Overall, 49.3% of patients had normal estimated glomerular filtration rate (eGFR >90 mL/min/1.73 m[2]), 34.7% showed mildly reduced eGFR (90-60), and 16% exhibited marked eGFR reduction (<60). Among patients with normal eGFR, the combined mean prevalence (mean ± SD) of abnormal TDBs, UACr, and UPCr was 29.7 ± 4.9%, indicating early tubular injury. Temporal analysis revealed a higher prevalence of TDB abnormalities at 6-MPC, whereas glomerular dysfunction was more pronounced at 24-MPC. These findings suggest that renal injury in long COVID is more prevalent than previously recognized and that TDB assessment may improve early detection of kidney damage.},
}
@article {pmid41827411,
year = {2026},
author = {Guzmán-Gurrola, AL and González-López, L and Chávez-Íñiguez, JS and Verduzco Vázquez, M and Flores-Hernández, EI and Novoa-Burquez, JA and Zavala-Cerna, MG},
title = {Sex-Specific Differences in Nutritional Status and Olfaction in Association with Cognitive Impairment Amongst Older Adults with Long COVID Syndrome.},
journal = {Journal of clinical medicine},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/jcm15051994},
pmid = {41827411},
issn = {2077-0383},
abstract = {Background/Objectives: Long COVID has emerged as a significant public health concern, characterized by persistent symptoms following SARS-CoV-2 infection. Cognitive impairment is a common sequela, particularly among older adults (OAs). Although olfactory dysfunction and malnutrition have been previously associated with cognitive decline, it remains elusive to what extent sex-specific variations in these and additional factors will be pivotal to guiding targeted interventions in a sex-specific manner. To fill this gap in knowledge, we undertook a study with the purpose of investigating the contribution of sex-specific risk factors to the development of cognitive impairment (CI) in a cohort of OAs hospitalized with long COVID. Methods: We undertook a cross-sectional study among OAs hospitalized at a geriatric care unit. Olfactory function was assessed using the Sniffin' Stick Test. Cognitive impairment was evaluated by the Mini-Mental State Examination, and nutritional status was assessed with the Mini Nutritional Assessment (MNA). Statistical analyses included linear regression. Results: A total of 45 patients with long COVID were included, of whom 51% were female. The prevalence of CI was lower in men compared to women. In the single variable analysis, nutritional factors were associated with CI only in women; importantly, the loss of olfactory function was associated with CI in the whole group and to CI in women after multivariate analysis. Conclusions: Olfactory dysfunction is a potential biomarker for cognitive impairment in OAs with long COVID in a sex-specific manner. In our study nutritional status and probable obesity could be additional factors associated with CI; nevertheless, this was not confirmed in our multivariate analysis; therefore, this hypothesis would need to be tested in larger studies.},
}
@article {pmid41827401,
year = {2026},
author = {Tremblay, C and Bauer, UMM and Beudt, J and Orwat, S and Diller, GP and Pfitzer, C and Helm, PC},
title = {The Impact of Acute COVID-19 Infection and Long COVID in Patients with Congenital Heart Disease: A Longitudinal Study by the German National Register for Congenital Heart Disease.},
journal = {Journal of clinical medicine},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/jcm15051986},
pmid = {41827401},
issn = {2077-0383},
abstract = {Background: Patients with congenital heart disease (CHD) were considered to belong to a vulnerable group at risk for COVID-19 infection. Our aim was to investigate the severity of acute COVID-19 infection in this patient group as well as the occurrence of sequelae. Methods: We performed telephone interviews with all accessible COVID positive CHD patients from our online COVID-19 patient survey. Baseline information was extracted from our nationwide data bank, with further details from hospital discharge letters. Results: Ninety-nine patients (or parents) were interviewed (male 50.5%): 28 children, 32 young adults (up to 29 years), and 39 adults (30 years and above). Twenty patients had simple, 38 moderate, and 41 complex CHD (10.1% were cyanotic). In twelve patients the CHD was native, ten underwent univentricular palliation, and the rest had corrective cardiac treatment. Thirty patients had additional non-cardiac risk factors. The acute course of COVID-19 was mild in 50, moderate in 38, and severe in three patients, requiring hospitalization. No deaths occurred. Long COVID symptoms (persisting ≥ 12 weeks) were reported by 31 patients. Conclusions: Despite underlying CHD, the severity of the acute course of COVID-19 in our cohort is comparable to that in the general population. Even patients with cyanotic CHD, complex CHD after univentricular palliation, or those with pulmonary hypertension, usually had a mild to moderate course, so that hospitalization was rarely necessary. The percentage of CHD patients reporting Long COVID symptoms (31%) was higher than in the general population. The long-term impact of COVID-19 and Long COVID in CHD patients is unknown and remains to be investigated.},
}
@article {pmid41826684,
year = {2026},
author = {Pérez Chacón, G and Mascaro, S and Estcourt, MJ and Phetsouphanh, C and Nicholson, AE and Snelling, T and Wu, Y},
title = {Developing a general research framework for long COVID using causal modelling.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01488-8},
pmid = {41826684},
issn = {2730-664X},
abstract = {BACKGROUND: Long COVID is an infection-associated chronic condition with uncertain evolution, leading to ambiguity in case definitions and various hypotheses about its pathophysiology. Despite this diversity, causal models may offer a unified understanding of post-acute COVID-19 mechanisms. This study aimed to examine whether dynamic Bayesian networks could facilitate inferences on long COVID.<br><br>METHODS: Using a causal engineering approach, we developed directed acyclic graphs and qualitatively parametrised them as Bayesian networks to depict the hypothesised mechanisms of long COVID in a theory-agnostic manner. Based on the literature and expert knowledge, we created a general modelling framework summarising biological pathways from mild or severe COVID-19 to the development of respiratory symptoms and fatigue over four key periods (t1 to t4). We used qualitative parametrisation for design and validation, and tested the framework against four scenarios: A) mild COVID-19 at t1 (start of acute infection); B) severe acute COVID-19 at t1; C) symptoms reported at t1 (acute COVID-19 disease); and D) symptoms reported at t1 and t3 (e.g., 3-to-6 months post-acute infection), indicating long COVID.<br><br>RESULTS: Here we show that, in scenario A, the probability of progressing to severe disease and developing persistent organ dysfunction 1-to-2 years post-acute COVID-19 was lower than in scenario C. Those reporting symptoms at t1 and t3 have the highest probability of developing persistent organ dysfunction beyond the acute infection period.<br><br>CONCLUSIONS: Our findings lay the foundations for a better understanding of the progression of long COVID syndromes. Illustrative simulations support the use of causal models to help address both diagnostic and prognostic questions in long COVID research.},
}
@article {pmid41826107,
year = {2026},
author = {Ganmaa, D and Cook, KA and Khudyakov, P and Enkhjargal, D and Bilegtsaikhan, T and Mayer, KH and Clar, A and Rueschman, M and Balasubramanian, R and Hazra, A and Sesso, HD and Stone, VE and Copeland, P and Friedenberg, G and Smith, DC and Lei, Q and Lee, T and McDonald, EG and Enkhtsetseg, T and Sumiya, E and Narankhuu, Y and Erdenetuya, M and Tserendagva, D and Landberg, R and Roxhed, N and Lagerström, SR and Manson, JE},
title = {A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101398},
doi = {10.1016/j.tjnut.2026.101398},
pmid = {41826107},
issn = {1541-6100},
abstract = {BACKGROUND: Data from randomized controlled trials of vitamin D3 supplementation in modifying the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse.<br><br>OBJECTIVES: We evaluated the effect of vitamin D3 supplementation on healthcare utilization and other clinical outcomes among adults with coronavirus disease 2019 (COVID-19) and their close contacts.<br><br>METHODS: We conducted a parallel 2-group randomized controlled double-blinded trial targeting free-living adults in the United States and Mongolia. Index participants with newly diagnosed COVID-19 were cluster-randomized with up to one of their cohabiting contacts either to an oral vitamin D3 loading dose of 9600 IU/d for 2 d followed by 3200 IU/d for 4 wk or to placebo. Participants completed weekly questionnaires on healthcare utilization, disease severity, and long COVID (index participants) or new SARS-CoV-2 infection (household contacts). The primary outcome was &#x2265;1 healthcare visits (including hospitalization) or death within 4 wk among the index participants.<br><br>RESULTS: Index participants (n = 1747) were a median of 38.0 y old (IQR: 31.1-47.0), 65.6% female/other sex, 4.2% Black non-Hispanic, 4.8% Hispanic/Latinx, 43.2% Asian, 44.3% non-Hispanic White, and 44.9% vitamin D deficient or insufficient (25-hydroxyvitamin D3 <20 ng/mL). Baseline characteristics for the household contacts (n = 277) were similar. The 4-wk cumulative incidence of healthcare utilization in index participants did not significantly differ between the vitamin D3 (n = 863) and placebo (n = 884) groups [cumulative incidences, 0.28 compared with 0.29; odds ratio (OR), 0.97; 95% confidence interval (CI): 0.75, 1.24]. Similar nonsignificant results were observed for the prespecified secondary treatment and prevention outcomes, though per-protocol analyses showed a nonsignificant trend toward benefit of vitamin D3 on the prevalence of long COVID at 8 wk (OR, 0.78; 95% CI: 0.59, 1.03). No safety concerns were identified.<br><br>CONCLUSIONS: Among adults with newly diagnosed SARS-CoV-2 infections, vitamin D3 supplementation did not significantly change the 4-wk cumulative incidence of healthcare utilization or COVID-19-related outcomes compared with placebo. Promising results for long COVID warrant further study. This study was registered at clinicaltrials.gov as NCT04536298. First registered on 1 September, 2020.},
}
@article {pmid41825703,
year = {2026},
author = {Boniface, ER and Alvergne, A and Darney, BG and Benhar, E and van Lamsweerde, A and Edelman, A},
title = {Menstrual cycle patterns during acute and long COVID-19 infection among a cohort of individuals with regular menstrual cycles.},
journal = {American journal of obstetrics and gynecology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajog.2026.03.001},
pmid = {41825703},
issn = {1097-6868},
}
@article {pmid41825193,
year = {2026},
author = {Costantino, V and Notaras, A and MacIntyre, CR},
title = {Long COVID in children in Australia and the potential impact of vaccination.},
journal = {Vaccine},
volume = {79},
number = {},
pages = {128442},
doi = {10.1016/j.vaccine.2026.128442},
pmid = {41825193},
issn = {1873-2518},
abstract = {Long COVID (LC) or Post-COVID condition (PCC) is a serious illness that can result in chronic conditions in all ages, including children. We used SARS-CoV-2 infection-induced data to find monthly seroprevalence in 6 months to 11 year olds in 2021-2022 to estimate the proportion experiencing PCC. A non-dynamic model using age-specific PCC rates, in accordance with the WHO definition of LC and the National Academies of Sciences, Engineering, and Medicine (NASEM) definition of PCC, was applied to estimate the burden of LC in children during 2021-2023 and to evaluate the impact of vaccination under different coverage and vaccine effectiveness (VE) scenarios. By the end of 2022, seroprevalence was higher among children aged 5-11 years (85.6%) than among those aged 6 months-4 years (77.9%). However, a higher proportion of the youngest age experienced LC (approximately 0.8%), compared with children aged 5-11 year (approximately 0.3%). The low vaccination coverage achieved in the 5-11 age group (40%) averted approximately 9% of infections and reduced LC prevalence by 13% at the end of 2022 under the assumption of no waning VE. If children aged 6 months-4 years age group, who were ineligible for routine vaccination, had been vaccinated at the same uptake level, infections and LC prevalence could have been reduced by approximately 5% and 10%, respectively. Achieving coverage comparable to that of adults aged 70 years and older (94%) would have resulted in substantially larger reductions in infections (∼ 32%-55%) and LC prevalence (∼34%) in both paediatric age groups. However, assuming VE waning 12% per month, the reduction in seroprevalence and LC prevalence are limited to 2-4%, depending on coverage. These findings suggest that vaccination can reduce LC burden in children, which should be considered in vaccine policy.},
}
@article {pmid41824763,
year = {2026},
author = {Bachelet, VC and Jiménez-Paneque, R and Gomolán, P and Silva-Ayarza, I and López Nitsche, M and Andrades, CO and Carroza, B and Morgado, B},
title = {Validation of the cultural adaptation of the "Long Coronavirus Disease (COVID) Symptom and Impact Tools" for the Chilean population.},
journal = {Medwave},
volume = {26},
number = {2},
pages = {e3205},
doi = {10.5867/medwave.2026.02.3205},
pmid = {41824763},
issn = {0717-6384},
mesh = {Humans ; Chile ; *COVID-19/diagnosis/physiopathology/complications ; Reproducibility of Results ; Male ; Female ; Middle Aged ; Adult ; Translations ; Aged ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: The Long Coronavirus Disease (COVID) Symptom and Impact Tools (ST and IT) are self-administered instruments designed to monitor symptoms and the impact of long COVID. We translated and culturally adapted these tools for use in Chile. This study evaluated internal consistency and test-retest reliability for the IT, described reported symptoms with the ST, and explored changes over time.<br><br>METHODS: The first phase, previously published, involved translation and cultural adaptation. The second phase included 28 patients with persistent COVID-19 symptoms; 20 completed a second assessment. The IT assesses impact using six items, each scored 0-10 (total 0-60). The ST lists 53 symptoms across ten categories. Internal consistency of the IT was assessed using Cronbach's alpha and item-consistency indicators. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC, 95% CI) and a Bland-Altman analysis. ST responses were summarized with absolute and relative frequencies and confidence intervals.<br><br>RESULTS: The IT showed excellent internal consistency (Cronbach's alpha 0.945; 95% CI 0.906-0.971). Test-retest reliability was acceptable (ICC 0.72; 95% CI 0.43-0.88), with minimal bias in the Bland-Altman plot. General, neurological, thoracic, and ear-nose-throat symptoms were the most frequent. Participants reported a mean of 19 symptoms, with no significant differences between visits.<br><br>CONCLUSIONS: The adapted tools demonstrated acceptable psychometric properties and appear suitable for use in Chile. Symptom reporting was extensive, underscoring the need for larger studies to confirm these findings.},
}
@article {pmid41824149,
year = {2026},
author = {M van der Feltz-Cornelis, C},
title = {Cognition and Long COVID: a Review.},
journal = {Current neurology and neuroscience reports},
volume = {26},
number = {1},
pages = {},
pmid = {41824149},
issn = {1534-6293},
}
@article {pmid41823222,
year = {2026},
author = {Shapira, S and Vishnevsky, G and Yaakobi, H and Shenberg, G and Motlaq, M and Liberman, E and Kalisky, A and Benari, G and Tsiodras, S and Adi, N and Lötvall, J and Arber, N},
title = {Reduced Mortality in COVID-19 Patients Treated With Inhaled Extracellular Vesicles Expressing CD24.},
journal = {Journal of extracellular vesicles},
volume = {15},
number = {3},
pages = {e70253},
doi = {10.1002/jev2.70253},
pmid = {41823222},
issn = {2001-3078},
support = {74260//Israel Innovation Authority/ ; },
mesh = {Humans ; Male ; Female ; *Extracellular Vesicles/metabolism ; *COVID-19/mortality/therapy ; Middle Aged ; Retrospective Studies ; *CD24 Antigen/administration &amp; dosage/therapeutic use/metabolism ; Aged ; Administration, Inhalation ; SARS-CoV-2 ; Quality of Life ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Severe COVID-19, and other systemic infections, can trigger hyperinflammation leading to lung injury. EXO-CD24, an inhaled extracellular vesicle therapy with anti-inflammatory properties, has shown acute clinical benefit, but long-term effects on survival remain unknown.<br><br>METHODS: We compared the mortality in 35 patients with moderate-to-severe COVID-19 treated with inhaled EXO-CD24 on five consecutive days in 2020, versus 105 matched controls receiving standard care (1:3 ratio). This 'real life' study was a retrospective follow-up extended to 4.6&#xa0;years after infection, evaluating all-cause mortality as well as health-related quality of life in survivors (HRQoL).<br><br>RESULTS: No deaths occurred in the EXO-CD24 group (0/35) versus 14 deaths (13.3%) among the matched controls (p&#xa0;<&#xa0;0.05). The survival difference was most marked in the first month but persisted over time. At the end of the follow-up, theEXO-CD24 patients reported significantly better HRQoL, including well-being, physical function, and mobility.<br><br>CONCLUSIONS: Repeated inhalations with EXO-CD24 is associated with improved survival and HRQoL up to 4.6&#xa0;years post-treatment. These findings suggest durable benefits and support further evaluation of EXO-CD24 as an immunomodulatory therapy in severe inflammatory conditions.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04657497.},
}
@article {pmid41822694,
year = {2026},
author = {Butzin-Dozier, Z and Kumar, M and Ji, Y and Wang, LC and Anzalone, AJ and Hurwitz, E and Patel, RC and Wong, R and Bramante, C and Sines, B},
title = {IL-6 Receptor Antagonists and Severe Post-COVID-19 Outcomes: An Emulated Target Trial.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.27.26347274},
pmid = {41822694},
abstract = {BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a key role in systemic hyperinflammation and may mediate the relationship between acute COVID-19 and severe long-term outcomes such as Long COVID or death. IL-6 modulating drugs may reduce patients' risk of severe post-COVID-19 outcomes.<br><br>METHODS: We conducted an emulated target trial in a retrospective cohort of patients with moderate-to-severe rheumatoid arthritis who were prescribed IL-6 receptor antagonists (sarilumab or tocilizumab, pooled treatment) or other biologic agents (anakinra or baricitinib, pooled comparator) in 2022. We compared the 12-month cumulative incidence of mortality and Long COVID (diagnosed and probable) between groups using Super Learner and targeted maximum likelihood estimation, adjusting for covariates of interest.<br><br>RESULTS: In our cohort of 3,553 patients, we found that prescription of IL-6 receptor antagonists was associated with a lower 12-month cumulative mortality (adjusted relative risk (aRR) 0.40, 95% CI 0.27, 0.59), diagnosed Long COVID aRR 0.42, 95% CI 0.23, 0.78), and probable Long COVID (aRR 0.71, 95% CI 0.61, 0.83), compared to prescription of other biologic agents, among rheumatoid arthritis patients.<br><br>CONCLUSIONS: IL-6 receptor antagonists may prevent the incidence of severe post-COVID-19 outcomes, such as Long COVID or mortality. This supports the hypothesis that IL-6 may be a mechanistic biomarker of COVID-19 sequelae and that acute COVID-19 severity may mediate this relationship.},
}
@article {pmid41822518,
year = {2026},
author = {Shahbaz, S and Bozorgmehr, N and Rahmati, A and Abouda, A and Syed, H and Osman, M and Elahi, S},
title = {Single-cell analysis reveals immune remodeling of monocytes, NK cells, T cell exhaustion, and Galectin-9-associated depletion of gamma delta and mucosal-associated invariant T cells in Long COVID with ME/CFS.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1745933},
pmid = {41822518},
issn = {1664-3224},
mesh = {Humans ; *Killer Cells, Natural/immunology ; *COVID-19/immunology/complications ; Female ; Single-Cell Analysis ; *Mucosal-Associated Invariant T Cells/immunology ; *Monocytes/immunology ; *SARS-CoV-2/immunology ; *Galectins/immunology/metabolism ; Middle Aged ; Adult ; Receptors, Antigen, T-Cell, gamma-delta/immunology/metabolism ; T-Cell Exhaustion ; },
abstract = {INTRODUCTION: The cellular mechanisms underlying Long COVID (LC) associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain poorly understood.<br><br>METHODS: We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells collected 12 months after acute COVID-19 infection from female individuals with LC-ME/CFS and recovered (R) individuals. Comparative analysis was also performed using publicly available scRNA-seq datasets from idiopathic ME/CFS patients.<br><br>RESULTS: Based on transcriptional signatures, LC-ME/CFS patients exhibited a marked reduction in na&#xef;ve CD4[+] and CD8[+] T cells, regulatory T cells, MAIT cells, and &#x3b3;&#x3b4; T cells, accompanied by an expansion of effector T cells. NK cells displayed reduced frequency and altered activation-associated transcriptional factors, consistent with impaired cytotoxic potentials. B cells in LC patients exhibited gene expression profiles indicative of heightened activation, while plasma cells revealed a distinct transcriptional subset expressing NK-associated genes. Platelets and low-density neutrophils were expanded and exhibited enrichment of activated-related transcripts. Monocyte subsets demonstrated transcriptional skewing characterized by reduced expression of phagocytosis-associated genes and increased expression of pro-inflammatory cytokine-related genes/pathways. In contrast, idiopathic ME/CFS patients exhibited less pronounced immune alterations at the transcriptional level: while T cell activation was evident, there was no reduction in MAIT or NK cells, nor signs of T cell exhaustion. Notably, FOXP3 expression was upregulated, and B cells and platelets demonstrated dysregulated signatures in idiopathic ME/CFS. Mechanistically, we identify Galectin-9-TIM-3 interaction as a potential pathway driving &#x3b3;&#x3b4; and MAIT cell depletion in LC.<br><br>CONCLUSION: Our results reveal extensive peripheral immune remodeling in LC-ME/CFS, distinct from idiopathic ME/CFS, and support a model of chronic immune activation and dysregulation. Our findings offer a cellular framework for understanding LC pathogenesis and point to potential biomarkers and therapeutic targets for intervention.},
}
@article {pmid41822471,
year = {2026},
author = {Currey, J and Wang, C and Mayer, MG and Chen, Y and Nisperuza Vidal, AK and Allen, MJ and Khatun, MS and Ellsworth, CR and Islamuddin, M and Evangelista, J and Minor, SM and Golden, N and Zwezdaryk, KJ and Maness, NJ and Blair, RV and Kolls, JK and Pociask, DA and Fischer, T and Qin, X},
title = {Characterization of subchronic lung and brain consequences caused by mouse-adapted SARS-CoV-2 and influenza A infection of C57BL6 mice.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1755141},
pmid = {41822471},
issn = {1664-3224},
mesh = {Animals ; Mice ; *SARS-CoV-2/physiology ; Mice, Inbred C57BL ; *Lung/pathology/virology/immunology/metabolism ; *COVID-19/pathology/immunology/virology ; *Brain/virology/pathology/immunology/metabolism ; *Influenza A virus/physiology ; *Orthomyxoviridae Infections/pathology/immunology/virology ; Disease Models, Animal ; Female ; },
abstract = {INTRODUCTION: SARS-CoV-2 and, to a lesser extent, influenza A can lead to long-term complications in the respiratory and nervous systems. However, the mechanisms driving post-viral sequelae remain poorly understood.<br><br>METHODS: To address this gap, we longitudinally characterized C57BL/6 mice infected with sublethal doses of mouse-adapted SARS-CoV-2 (MA30) or influenza A (PR8). Lung and brain tissues were analyzed at 14-, 21-, and 28-days post-infection (DPI) using histological analysis and bulk-RNA sequencing.<br><br>RESULTS: In the lungs, both infections caused prolonged inflammation and fibrosis. MA30-infected lungs showed persistent upregulation of inflammation, coagulation, complement, as well as fibrotic, and extracellular matrix (ECM) remodeling pathways at 21 DPI, alongside downregulation of epithelial junction and metabolic program pathways. In contrast, PR8-infected lungs exhibited a strong acute interferon response and chronic upregulation of basal epithelial markers (e.g., Krt5, Krt14), consistent with epithelial regeneration. Notably, only PR8-infected mice displayed KRT5+ progenitor cell migration into damaged lung regions, indicating divergence in repair mechanisms. Neither MA30-infected, nor PR8-infected mice had detectable brain infection. However, MA30 mice, but not PR8-infected mice exhibited an elevated frequency of microhemorrhages at early timepoints and marked neuroinflammation at all timepoints. Transcriptomic profiling of MA30-infected brains showed enrichment for up-regulation of ECM remodeling, vascular dysfunction, IL6-signaling pathways along with a virus-specific disruption of the hypothalamic-pituitary axis with MA30 infection not seen in PR8-infected brains. These included genes linked to neuroinflammation, sensory processing disruption, and microvascular injury, mirroring clinical features of Long COVID.<br><br>DISCUSSION: Together, these findings establish distinct tissue-specific trajectories of long-term pathology following SARS-CoV-2 and influenza infection and provide a foundation for dissecting the mechanisms of post-viral lung and brain disease.},
}
@article {pmid41820938,
year = {2026},
author = {Zhang, Z and Xue, Y and Gao, L and Guan, L and Zhang, H and Ma, H and Li, X and Li, J and Yang, H and Tong, Z},
title = {Associated factors and predictive nomogram of long COVID: a cross-sectional study in China.},
journal = {BMC pulmonary medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12890-026-04221-2},
pmid = {41820938},
issn = {1471-2466},
support = {2023YFC0872500//Ministry of Science and Technology of the People's Republic of China/ ; BJRID2024-008//Beijing Research Center for Respiratory Infectious Diseases Projec/ ; 062//Beijing Scholars Program/ ; },
}
@article {pmid41820731,
year = {2026},
author = {Su, H and Keller, B and Danesh, V and McPeake, J and Boehm, LM and Eaton, TL and Mart, MF and Patel, MB and Ely, EW},
title = {Long COVID and the Challenge of Long-Term Employment: An Ecological, Sequential Explanatory Mixed-Methods Approach.},
journal = {Journal of occupational rehabilitation},
volume = {},
number = {},
pages = {},
pmid = {41820731},
issn = {1573-3688},
abstract = {PURPOSE: To identify and contextualize the determinants of long-term employment, health, and financial outcomes among individuals affected by Long COVID.<br><br>METHODS: Sequential explanatory mixed-methods study design guided by the social-ecological model. Adults with Long COVID who were employed before infection and returned to work during the three-year follow-up were recruited through in-person and virtual outpatient venues: ResearchMatch, a Long COVID clinic, and a peer support group affiliated with a medical center. Participants completed validated surveys assessing factors influencing sustained employment. Stratified semi-structured interviews were then conducted to explore how these factors shaped sustained employment. Quantitative data were analyzed using descriptive and inferential statistical methods, while qualitative data were analyzed through content analysis.<br><br>RESULTS: Among 79 participants who returned to work, 58% (n&#x2009;=&#x2009;46) remained employed after a mean follow-up of 1,077&#xa0;days. Those still employed reported reduced capacity and persistent uncertainty. Those no longer employed experienced worse physical health (p&#x2009;<&#x2009;0.002), greater comorbidity burden (p&#x2009;=&#x2009;0.01), more environmental barriers (p&#x2009;=&#x2009;0.02), and increased financial hardship (p&#x2009;=&#x2009;0.03). Qualitative analyses identified nonlinear return-to-work trajectories shaped by fluctuating and often invisible symptoms, alongside multilevel themes influencing employment sustainability, including misalignment between functional capacity and job demands, challenges obtaining workplace accommodations, stigma, limited policies, and labor market barriers.<br><br>CONCLUSIONS: Employment sustainability among individuals with Long COVID is shaped by complex, multilevel barriers, with job loss further worsening health and financial hardship. Investment in comprehensive Long COVID care, including multidisciplinary clinical services, vocational rehabilitation, clinician education, public awareness initiatives, employer training, and policy reform, is critical to support long-term recovery and employment sustainability.},
}
@article {pmid41819071,
year = {2026},
author = {He, K and Simmonds, AJ},
title = {Gut check: Peroxisomes as a missing link in long COVID intestinal repair.},
journal = {Developmental cell},
volume = {61},
number = {3},
pages = {466-467},
doi = {10.1016/j.devcel.2026.02.011},
pmid = {41819071},
issn = {1878-1551},
mesh = {*Peroxisomes/metabolism ; Humans ; Animals ; *COVID-19/virology/pathology/metabolism ; *SARS-CoV-2 ; *Intestines/virology/pathology ; Signal Transduction ; },
abstract = {Long COVID is often associated with persistent gastrointestinal dysfunction. In this issue of Developmental Cell, Wang et al. reveal that intestinal SARS-CoV-2 reservoirs disrupt VLCFA-mediated peroxisome signaling needed for epithelial repair. Patient studies, combined with Drosophila and mammalian models, identify an underlying mechanism and FDA-approved peroxisome activators as potential therapeutics.},
}
@article {pmid41816409,
year = {2026},
author = {Chai, X and Qi, H and Liu, X and Zhou, F and Jiang, Y and Wu, M and Lian, S and Wang, L and Bao, Y},
title = {A narrative review of SARS-CoV-2 variants and long COVID.},
journal = {Journal of thoracic disease},
volume = {18},
number = {2},
pages = {164},
pmid = {41816409},
issn = {2072-1439},
abstract = {BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of the pandemic, there has been a continuous rise in cases of both COVID-19 and long COVID. It is acknowledged that long COVID is a multisystem disorder with a wide range of symptoms; its primary symptoms and indicators include fatigue, dyspnea, anosmia, myalgia, cough, and hyposmia. SARS-CoV-2 has continuously evolved since the wild strain first appeared, resulting in numerous genetic variants. These strains exhibit significant differences in terms of pathogenicity and immune evasion. Key scientific questions remain regarding whether and how these variations influence the development and clinical course of long COVID. This review aims to examine associations between SARS-CoV-2 strains and long COVID, synthesize current evidence, identify research gaps, and provide recommendations for subsequent rehabilitation treatments.<br><br>METHODS: Literature searches were conducted using PubMed, focusing on publications from January 2020 to August 2025. Relevant literature on long COVID and SARS-CoV-2 variants was systematically reviewed and summarized, and included in this review.<br><br>KEY CONTENT AND FINDINGS: This review highlights the ongoing genetic evolution of SARS-CoV-2 as a key temporal dynamic during the pandemic. Different SARS-CoV-2 variants result in varying severity of long COVID. Anti-inflammatory treatments demonstrate significant efficacy for long COVID patients. COVID-19 vaccination prior to SARS-CoV-2 infection reduces the risk of long COVID, and another successful treatment option for persistent COVID symptoms is physical therapy.<br><br>CONCLUSIONS: Long COVID remains a significant public health challenge. The relationship between SARS-CoV-2 variants and long COVID requires further elucidation. This condition may cause significant economic and medical burdens in the future. To completely protect the physical and mental health of long COVID patients, it is essential to broaden therapeutic options and create individualized therapy programs. Therefore, understanding the connection between long COVID and SARS-CoV-2 variants is crucial. Based on this knowledge, effective strategies must be designed to empower individuals in proactively addressing and managing long COVID.},
}
@article {pmid41816007,
year = {2026},
author = {Park, J and Hwang, W and Lee, S and Lee, HC and MacMahon, M and Zilbauer, M and Han, N},
title = {Advancing understanding of long COVID pathophysiology through quantum walk-based network analysis.},
journal = {Bioinformatics advances},
volume = {6},
number = {1},
pages = {vbag050},
pmid = {41816007},
issn = {2635-0041},
abstract = {MOTIVATION: Long COVID is a multisystem condition characterized by persistent symptoms such as fatigue, cognitive impairment, and systemic inflammation following COVID-19 infection. However, its mechanisms remain poorly understood. In this study, we applied the quantum walk, a computational approach leveraging quantum interference, to explore large-scale SARS-CoV-2-induced protein networks.<br><br>RESULT: Compared to the conventional random walk with restart method, the quantum walk demonstrated superior capacity to traverse deeper regions of the network, uncovering proteins and pathways implicated in Long COVID. Key findings include mitochondrial dysfunction, thromboinflammatory responses, and neuronal inflammation as central mechanisms. Quantum walk uniquely identified the CDGSH iron-sulfur domain-containing protein family and VDAC1, a mitochondrial calcium transporter, as critical regulators of these processes. VDAC1 emerged as a potential biomarker and therapeutic target, supported by FDA-approved compounds such as cannabidiol. These findings highlight quantum walk as a powerful tool for elucidating complex biological systems and identifying novel therapeutic targets for conditions like Long COVID.<br><br>The code and input data that were used for this study are available at https://github.com/Namshik-Han-Lab/QuantumWalk-LongCovid.},
}
@article {pmid41814585,
year = {2026},
author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A and Filip, R and Soldanescu, I and Mangul, S and Dimian, M},
title = {Management of long COVID-19 in children and adolescents: from diagnosis to therapeutically approaches.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2642510},
doi = {10.1080/07853890.2026.2642510},
pmid = {41814585},
issn = {1365-2060},
mesh = {Humans ; *COVID-19/therapy/complications/diagnosis ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long Coronavirus disease 2019 (COVID-19), also termed post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), has emerged as a complex multisystem condition in children and adolescents worldwide. It can occur even after mild or asymptomatic acute infections, with symptoms that may persist, fluctuate, or relapse over time. This review aims to comprehensively explore the characteristic manifestations, management and current therapeutic possibilities of pediatric Long COVID-19 (L-C19).<br><br>METHODS: A systematic search was conducted in multiple databases such as PubMed, Scopus, Web of Science, and Google Scholar, for literature published between January 2020 and October 2025.<br><br>RESULTS: Diagnosing pediatric L-C19 is challenging due to the heterogeneity of symptoms and lack of specific diagnostic biomarkers. Most young patients experience gradual improvement over months, but a significant subset remains symptomatic for >1&#x2009;year with substantial disability, underscoring the need for timely diagnosis and intervention. Current clinical consensus emphasizes an individualized, multidisciplinary management approach focused on symptom relief and functional rehabilitation. No definitive cure exists for L-C19; thus, care is tailored to each patient's predominant issues. Therapeutic strategies combine supportive self-management (e.g. energy conservation and pacing) with both non-pharmacological and pharmacological interventions. Multimodal rehabilitation programs - including graded exercise therapy and cognitive behavioral therapy - have shown promise in improving fatigue, mental health, and overall quality of life. Targeted treatments for specific sequelae (such as autonomic dysfunction or chronic pain) are applied on a case-by-case basis, although high-quality evidence for medications remains limited. Globally, interdisciplinary collaborations have been established to provide harmonized diagnostic and treatment protocols, and major research initiatives are underway to evaluate novel therapies and include children in L-C19 clinical trials.<br><br>CONCLUSION: Ongoing international efforts to develop standardized diagnostic tools, outcome measures, and evidence-based interventions are crucial to optimize care and long-term outcomes for children and adolescents affected by L-C19.},
}
@article {pmid41814565,
year = {2026},
author = {Clarke, Z and Cowan, H and Rhodes, T and Fernes, P and Haines, A and Leal, L},
title = {Vital yet Fragile: Informal Networks of Support Among Young People Navigating Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70611},
doi = {10.1111/hex.70611},
pmid = {41814565},
issn = {1369-7625},
support = {13515//National Institute for Health and Social Care Research/ ; },
mesh = {Humans ; *COVID-19/psychology ; Adolescent ; Female ; Male ; Young Adult ; Qualitative Research ; *Social Support ; Adult ; United Kingdom ; Interviews as Topic ; SARS-CoV-2 ; Health Services Accessibility ; },
abstract = {INTRODUCTION: Young people living with Long Covid face challenges accessing health care and social support. Previous qualitative research in the UK has described the 'invalidation' of Long Covid illness experience. It has been said that there is a 'double invisibility' produced by narratives that minimise the effects of Covid-19 among young people, which combine with a generalised lack of awareness of Long Covid itself. In this analysis, we look beyond the well-documented networks of online self-help and advocacy to trace how young people navigate, connect and maintain multi-sited alternative care networks to manage their everyday experiences of Long Covid.<br><br>METHODS: We draw on the analysis of qualitative interviews with 54 young people aged 15-25 with long-term health impacts from Covid-19, of whom 30 also participated in follow-up interviews. The sample includes young people with multiple genders, who identify with a range of ethnic identities, and who have experience of neurodiversity or additional disabilities. Interview transcripts were analysed to identify key themes, in collaboration with a group of peer researchers who are co-authors on this study.<br><br>RESULTS: We find that the informal networks that are navigated and created by young people play a vital role, but that they are also fragile. We present our findings across four themes-how informal networks afford young people validation in different ways; the material differences informal networks bring to young people's lives; the work that young people do to build and maintain these networks; and the fragility of support networks. We show that informal networks are not simply identified and found, but that they are 'made to work' by young people who do the work that brings informal networks together and that holds them in place.<br><br>CONCLUSION: We conclude that there is a need to strengthen the vital work of informal care that is done by young people, but that alternative care networks should not be seen simply as a means of 'filling the gaps' of inadequate care. There is a need to build infrastructures that properly integrate formal with informal care in direct response to young people's experiences of Long Covid.<br><br>This qualitative study was undertaken in close collaboration with community partners and co-produced with young people affected by Long Covid, using participatory methods. Young people affected by Long Covid were involved in a series of consultations, workshops and meetings focused on the analysis of data and their development into project outputs, including as authors of this paper.},
}
@article {pmid41813046,
year = {2026},
author = {Njøten, KL and Magnussen, LH and Haugstvedt, A and Jürgensen, M and Kvale, G and Frisk, B},
title = {Exploring experiences following participation in a concentrated micro-choice-based rehabilitation programme for long covid: a focus group study.},
journal = {BMJ open},
volume = {16},
number = {3},
pages = {e105215},
doi = {10.1136/bmjopen-2025-105215},
pmid = {41813046},
issn = {2044-6055},
abstract = {OBJECTIVES: To explore how individuals with long covid experienced various aspects of a micro-choice-based rehabilitation programme and if these experiences could facilitate behaviour change.<br><br>DESIGN: A qualitative study with three focus groups was conducted, in mean 9.8 months after completing the rehabilitation programme. Data were analysed using systematic text condensation.<br><br>SETTING: The study was conducted in a university setting.<br><br>PARTICIPANTS: 19 participants (aged 23-55 years, 15&#x2009;women) were included between Spring 2021 and Autumn 2022.<br><br>INTERVENTION: The participants in this study had participated in a 3-day concentrated micro-choice-based rehabilitation programme. One of the main features of this intervention was to support participants in shifting their focus from targeting symptoms to choosing alternative actions aimed at improving everyday functioning, referred to as micro-choices.<br><br>RESULTS: Five themes were identified: (1) reduction in uncertainty achieved through reassurance and motivation; (2) 'in the same boat': sharing experiences and supporting each other; (3) knowledge about the body's stress responses and micro-choices; (4) shifting between individual practice and close collaboration with the therapists; and (5) sustaining behaviour change is challenging. These themes illustrated how participants' experiences with different aspects of the rehabilitation programme facilitated both the initiation and maintenance of behaviour change. The participants highlighted the importance of acknowledging their challenges, reducing fear, sharing experiences with peers, feeling understood and supported, collaborating with a skilled team, receiving personalised guidance and gaining insights through the exploration and implementation of micro-choices. Participants also highlighted that behaviour change is an ongoing process requiring sustained effort.<br><br>CONCLUSION: The findings showed how participants experienced various aspects of a concentrated micro-choice-based rehabilitation programme as supportive of behaviour change. The findings indicate that a concentrated rehabilitation programme may facilitate self-management and improve everyday function in individuals with long covid.<br><br>TRIAL REGISTRATION NUMBER: NCT05234281.},
}
@article {pmid41812698,
year = {2026},
author = {Naghibosadat, M and Hahn, E and Molinaro, S and Babuadze, G and Kozak, R},
title = {Comparison of SARS-CoV-2 Variant Pathogenicity in a Long-COVID Syrian Hamster Model.},
journal = {Virus research},
volume = {},
number = {},
pages = {199711},
doi = {10.1016/j.virusres.2026.199711},
pmid = {41812698},
issn = {1872-7492},
abstract = {The SARS-CoV-2 pandemic has infected over 700 million people, and a substantial proportion develop post-acute sequelae of COVID-19, a disorder marked by persistent, multi-organ symptoms. Elucidating the underlying pathophysiology; and how it varies by viral lineage; is critical for guiding therapy. Syrian golden hamsters develop transient but non-lethal illness that parallels human disease and are therefore a model to investigate post-acute phase pathology with different viral variants. Hamsterswere infection with WT (B1), Alpha (B.1.1.7) or Beta (B.1.351) variants and monitored for 28 days for clinical signs and viral shedding. Lungs, nasal turbinates, heart, kidneys and spleen were collected at 14- and 28-days post-infection for quantitative histopathological analysis. All viral variants produced similar acute disease, with peak viral loads on day 3 and maximal weight loss on day 7. Inflammation and fibrosis were evident in every infected group. Notably, WT and Alpha variants caused greater lung, cardiac, and renal fibrosis than the Beta variant, while splenic germinal-center expansion was most pronounced in animals infected with the Alpha variant. These findings establish that SARS-CoV-2 leaves variant-dependent post-acute multi-organ damage in hamsters, with WT and Alpha inducing the most severe pathology. This model captures variant-dependent post-acute organ injury and provides a quantitative framework for evaluating anti-fibrotic interventions.},
}
@article {pmid41810370,
year = {2026},
author = {Azhir, A and Cheng, J and Tian, J and Bassett, IV and Patel, CJ and Klann, JG and Murphy, SN and Estiri, H},
title = {The age paradox in post-infectious sequelae: physiological reserve outweighs chronological age in Long COVID susceptibility.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.24.26346989},
pmid = {41810370},
abstract = {BACKGROUND: Older age is widely considered a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC), typically attributed to immunosenescence and inflammaging. However, whether this association reflects intrinsic biological ageing or accumulated comorbidity burden remains unclear, with implications for clinical risk stratification.<br><br>METHODS: We conducted a retrospective cohort study using the Precision PASC Research Cohort (P2RC) from Mass General Brigham, comprising 133,792 COVID-19 patients from 12 hospitals and 20 community health centres in Massachusetts (March 2020-May 2024). PASC was ascertained using a validated computational phenotyping algorithm. We used generalised estimating equations with cluster-robust variance to model PASC risk, causal mediation analysis to decompose age effects through comorbidity burden and acute severity, and specification curve analysis across 768 analytical specifications to assess robustness.<br><br>FINDINGS: After adjustment for comorbidity burden, each decade of age was associated with 6% lower odds of PASC (OR 0.94; 95% CI 0.93-0.95). Causal mediation analysis revealed that comorbidities accounted for 145% of the total age effect, indicating inconsistent mediation wherein age's direct protective effect was masked by its indirect harm through chronic disease accumulation. This protection was age-dependent: adults younger than 65 years retained robust resilience independent of comorbidities (ADE:-0.0042, p<0.001), whereas adults 65 years and older showed complete loss of this protection (ADE: +0.0020, p=0.14).<br><br>INTERPRETATION: Long COVID susceptibility is driven by physiological reserve rather than chronological age until approximately age 65, beyond which age-related protective mechanisms become exhausted. Risk stratification should prioritise comorbidity burden over birth year in younger adults.<br><br>FUNDING: National Institute of Allergy and Infectious Diseases (NIAID).},
}
@article {pmid41809272,
year = {2026},
author = {Zarkadi, A and Katotomichelakis, M and Chaidas, K},
title = {Long-Term Olfactory Dysfunction in COVID-19 Patients: A Systematic Review.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e103143},
pmid = {41809272},
issn = {2168-8184},
abstract = {Olfactory dysfunction (OD) emerged early in the COVID-19 pandemic as a prevalent and often persistent symptom. While most individuals recover within weeks, a significant proportion continue to suffer from long-term impairments, including both quantitative and qualitative sensory deficits. Our review aimed to summarize current evidence on long-term post-COVID-19 OD with a duration of at least three months, including prevalence, recovery trajectory, and prognostic factors. The PubMed and Scopus databases were searched for relevant studies up to August 2024 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-one studies were ultimately included, involving over 4,000 individuals. A remarkable proportion of patients continue to experience persistent dysfunction post-infection for a period ranging from several months to over two years. Qualitative disorders, such as parosmia and phantosmia, frequently appeared during recovery. Prognosis seemed to be related to age, initial severity, duration of OD, co-existing symptoms, and potentially sex. A consistent discrepancy between subjective reports and objective psychophysical test results was observed. Methodological heterogeneity limited comparability across studies. Olfactory dysfunction is a significant and often overlooked long-term complication of COVID-19. Standardized diagnostic criteria, validated outcome measures, and prospective longitudinal research are urgently needed to guide evidence-based management and improve patient outcomes.},
}
@article {pmid41808916,
year = {2026},
author = {Jackson, ML and Weaver, MD and Varma, P and Czeisler, M&#xc9; and Booker, LA and McDonald, CF and Robbins, R and Ridgers, A and Lane, R and Rajaratnam, SMW and Czeisler, CA and Quan, SF and Howard, ME},
title = {Presentation and temporal nature of postacute sequelae of SARS-CoV-2 infection in a US national cohort.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {53},
number = {},
pages = {101205},
pmid = {41808916},
issn = {2666-3546},
abstract = {BACKGROUND: Postacute Sequelae of SARS-CoV-2 Infection (PASC) is a novel illness emerging from SARS-CoV-2 infection, characterized by the persistence of symptoms beyond resolution of the initial illness. Understanding the phenotypes and trajectory of PASC is critical for diagnosis and development of personalized management approaches for specific PASC syndromes, to ultimately improve quality of life. The aim of this study was to examine the prevalence and duration, and characterize patterns of specific PASC symptoms in a community-based cohort.<br><br>METHOD: A non-probabilistic, weighted, cross-sectional survey of 14,964 adults from the US general population from the COVID-19 Outbreak Public Evaluation (COPE) Initiative between March 10, 2022 and June 2, 2022.<br><br>RESULTS: At 1-month post-infection, 44% of individuals with a history of SARS-CoV-2 infection reported at least one physical symptom, 47% reported at least one mental health symptom and 33% reported at least one cognitive symptom (14%, 10%, and 17% in controls, respectively). The prevalence of specific physical, cognitive and mental health symptoms declined between 1- and 12-months post-infection, to a prevalence rate similar to non-infected controls by 12 months. Cluster analysis revealed the persistence of symptom groups, with loss of taste and smell, psychosocial symptoms, respiratory and cardiovascular symptoms, and brain fog the most prominent at 12 months. Although cognitive symptom clusters persisted to 6 months post-infection, mental health clusters were transient.<br><br>CONCLUSIONS: The prevalence of most common PASC symptoms fell to general population levels within 12 months. Persisting physical and cognitive symptom clusters provide insights into potentially distinct disease pathways, and are essential for guiding clinical management strategies, rehabilitation programs, and public health interventions aimed at mitigating long-term impacts of COVID-19.},
}
@article {pmid41806535,
year = {2026},
author = {Sansa, A and Cardesín, A and Campos, M and Rovira, C and de Haro, J and Yuste, E and Caballero-Borrego, M},
title = {Long COVID-19 olfactory dysfunction: discrepancy between psychophysical tests and self-perception.},
journal = {Brazilian journal of otorhinolaryngology},
volume = {92},
number = {3},
pages = {101797},
doi = {10.1016/j.bjorl.2026.101797},
pmid = {41806535},
issn = {1808-8686},
abstract = {OBJECTIVES: To evaluate the discrepancies between psychophysical olfactory tests and self-perceived smell function in consecutive patients with long COVID-19-related olfactory dysfunction, and to compare the characteristics of this impairment with those observed in other nasal conditions, in order to improve diagnostic accuracy and guide targeted treatment strategies.<br><br>METHODS: An observational study of 86 long COVID-19 patients assessed by the Barcelona Smell Test (BAST-24 Plus), Visual Analogue Scale (VAS), and the quality-of-life Sino-Nasal Outcome Test (SNOT-22). Results were compared with 120 healthy controls and 121 patients with chronic rhinosinusitis with Nasal Polyps (CRSwNP).<br><br>RESULTS: Long COVID-19 patients reported a mean VAS score of 6.34 and a SNOT-22 score of 26.43, with question 21 (smell) accounting for 12.67% of the total. No correlation was found between VAS and total SNOT-22 score, but a moderate positive correlation was observed with question 21 (r = 0.488, p < 0.001). BAST-24 Plus scores were significantly lower than in controls for Detection, Identification, and Correct Answer (p < 0.001). Compared to the CRSwNP group, long COVID-19 patients showed less impairment in Detection and Identification (p < 0.001). A stronger negative correlation was observed between VAS and Identification (r = -0.629, p < 0.0001) than with Detection (r = -0.482, p < 0.0001), suggesting that odor identification dysfunction has a greater impact on subjective perception.<br><br>CONCLUSIONS: The subjective perception of olfactory dysfunction does not correlate with psychophysical test results in long COVID-19 patients and is characterized by a predominantly identification-dominant quantitative impairment, which differs from other disorders showing detection-dominant impairment. These findings highlight the need for specific diagnostic and therapeutic strategies.<br><br>LEVEL OF EVIDENCE: III.},
}
@article {pmid41803812,
year = {2026},
author = {Wang, K and Ma, CH and Khoramjoo, M and Kung, JY and Oudit, GY},
title = {Taurine supplementation as a therapeutic strategy for cellular senescence and chronic inflammation in long COVID: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-13009-y},
pmid = {41803812},
issn = {1471-2334},
}
@article {pmid41803387,
year = {2026},
author = {Leitner, M and Ropele, S and Fellner, M and Koini, M},
title = {Intra and inter-network functional connectivity among long-Covid patients with ongoing disease duration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42000-5},
pmid = {41803387},
issn = {2045-2322},
}
@article {pmid41798842,
year = {2026},
author = {Duan, J and Zhang, J and Li, C and Li, Y and Yu, D and Chen, Y and Yang, Q and Lin, X and Cai, X},
title = {Fecal short-chain fatty acids and serum metabolites: the impact of COVID-19 infection on dialysis patients.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1772671},
pmid = {41798842},
issn = {2296-861X},
abstract = {INTRODUCTION: Patients undergoing dialysis are particularly susceptible to severe COVID-19 outcomes owing to pre-existing metabolic and immunological dysregulation, which may exacerbate clinical severity and elevate the risk of long COVID (LC). Nevertheless, the precise metabolic pathways implicated remain poorly characterized. This study aimed to characterize fecal short-chain fatty acids (SCFAs) and serum metabolomic signatures in dialysis patients with acute COVID-19 and to explore their association with LC.<br><br>METHODS: Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified fecal SCFAs in 27 infected patients and 28 non-infected controls, and untargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomics profiled serum samples from 23 infected patients and all 40 controls in partially overlapping patient subsets, with repeat serum sampling at 3 months and stratification into LC and non-LC groups. Multivariate analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Pearson correlation analyses between differential metabolites and routine clinical indicators were performed.<br><br>RESULTS: Infected patients exhibited significantly lower fecal levels of six SCFAs, including propionate and butyrate, compared with controls. Serum metabolomics identified 54 infection-related differential metabolites enriched in amino acid, energy, carbohydrate, and nucleotide metabolism, and 77 LC-associated metabolites predominantly mapping to amino acid and energy pathways. Pearson correlation analysis showed that amino acids and energy-supporting metabolites (e.g., glutamine, aspartate, methionine, cystine, taurine) were inversely correlated with C-reactive protein, leukocyte and neutrophil counts, and aspartate aminotransferase, but positively correlated with albumin, serum potassium, and lymphocyte or eosinophil counts, whereas purine degradation products and organic acids (e.g., uric acid, hypoxanthine, pyruvate, glycolate) exhibited the opposite pattern.<br><br>DISCUSSION: COVID-19 infection in dialysis patients is associated with marked depletion of fecal SCFAs and broad perturbations of systemic metabolism, with persistent amino-acid-centered alterations among patients who develop LC. These findings offer a novel metabolic framework supporting the implementation of prolonged follow-up strategies to monitor and ameliorate persistent sequelae in this high-risk population.},
}
@article {pmid41797113,
year = {2026},
author = {Shukla, A and Brahma, PK and Rajput, DS},
title = {Comment on "Association of Symptoms of neuropsychological long COVID with imaging and plasma biomarkers".},
journal = {Journal of the neurological sciences},
volume = {484},
number = {},
pages = {125841},
doi = {10.1016/j.jns.2026.125841},
pmid = {41797113},
issn = {1878-5883},
}
@article {pmid41796425,
year = {2026},
author = {Peñaherrera-Vásquez, D and Reina, A and Merlo, F and Fajardo-Loaiza, T and Zambrano-Sánchez, G and Rivadeneira, J and Fuenmayor-González, L},
title = {Unveiling the genitourinary phenotype of long COVID: a systematic review and meta-analysis.},
journal = {International urology and nephrology},
volume = {},
number = {},
pages = {},
pmid = {41796425},
issn = {1573-2584},
abstract = {IMPORTANCE: Long COVID has been associated with persistent multisystemic manifestations. However, genitourinary alterations have not been formally recognized as a distinct phenotype despite growing reports suggesting their relevance for long-term morbidity and quality of life.<br><br>OBJECTIVES: To determine the frequency and characteristics of genitourinary manifestations in patients with long COVID and to evaluate the evidence supporting the possible emergence of a genitourinary phenotype within long COVID.<br><br>DATA SOURCES: For this Systematic review and meta-analysis, a comprehensive search was conducted in PubMed (MEDLINE), Scopus, Web of Science, Embase, SciELO, and Bireme-BvS from inception to October 2025, without language or publication date restrictions. Observational studies (cross-sectional, cohort, or case-control) assessing individuals with one or more genitourinary symptoms-such as menstrual alterations, erectile dysfunction, urinary tract symptoms, or renal function decline-persisting&#x2009;&#x2265;&#x2009;12&#xa0;weeks after SARS-CoV-2 infection were included. Studies addressing only acute-phase manifestations, vaccine-related effects, or pre-existing genitourinary conditions were excluded.<br><br>DATA EXTRACTION AND SYNTHESIS: Data extraction was performed independently by two reviewers following PRISMA guidelines. Risk of bias (RoB) was assessed using the Joanna Briggs Institute checklist for prevalence studies. A random-effects meta-analysis using the Freeman-Tukey double arcsine transformation was applied to estimate pooled proportions, and heterogeneity was quantified using the I[2] statistic, Cochran's Q test, and the between-study variance (&#x3c4;[2]).<br><br>MAIN OUTCOMES AND MEASURES: The primary outcomes were the pooled frequencies of genitourinary manifestations in long COVID, including menstrual disorders, erectile dysfunction, and renal function decline.<br><br>RESULTS: Nine primary studies encompassing 2332 participants from eight countries were included. Most studies (88.9%) presented a low RoB. The pooled frequency of menstrual disorders was 49% (95% CI 24-74), erectile dysfunction 21% (95% CI 16-28), and renal function decline 29% (95% CI 20-39).<br><br>CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis provide evidence supporting the possible emergence of a genitourinary phenotype of long COVID, encompassing menstrual irregularities, erectile dysfunction, cystitis-like symptoms, and renal impairment. Recognition of this potential phenotype is crucial for improving diagnostic accuracy, patient follow-up, and multidisciplinary management. Further high-quality studies are warranted to elucidate the underlying mechanisms and long-term clinical implications.},
}
@article {pmid41747471,
year = {2026},
author = {Szwarcwald, CL and de Almeida, WDS and de Souza Junior, PRB and de Castilho, EA and Damacena, GN and Gomes, CS and Malta, DC},
title = {Impact of the COVID-19 pandemic on the health situation of the Brazilian population.},
journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases},
volume = {30},
number = {2},
pages = {105790},
pmid = {41747471},
issn = {1678-4391},
abstract = {INTRODUCTION: The analysis of COVID-19 mortality revealed that the Brazilian population was critically impacted by the pandemic. However, many knowledge gaps remain regarding COVID-19 morbidity in the country. This article aims to analyze the consequences of the coronavirus disease on health situation of the Brazilian population.<br><br>METHODS: This was a cross-sectional epidemiological online survey using an electronic questionnaire between July and December 2023. The sampling method used was the virtual Respondent Driven Sampling (RDS). Changes in socioeconomic conditions were assessed in the post-pandemic period. Anti-COVID-19 vaccination coverage, prevalence of SARS-CoV-2 infection were estimated, as well as of sequelae lasting three months or more (Long COVID) among confirmed cases. Associations of Long COVID with self-reported heath status, sleep disorders, and depressive symptoms were analyzed.<br><br>RESULTS: The sample included 3805 individuals 18-years or older. Regarding vaccination, 61.5 % (95 % CI: 58.0 %-65.0 %) stated they had received 3&#x2012;4 doses. In the post-pandemic period, 41.6 % faced financial difficulties. Prevalence of confirmed SARS-CoV-2 infection was 40.2 %, 6.4 % of respondents reported having had COVID-19, although not confirmed by test, and 15.3 % did not know if they had been infected with the coronavirus. Among those infected, 32.0 % (95 % CI: 28.8 %-35.3 %) reported Long COVID, 21.4 % reported a COVID-19-related illness, and 5.2 % needed and obtained hospitalization. Long COVID was associated with worsening self-rated health, sleep disorders, feelings of depression and 27.7 % were unable to perform their usual activities for one month or more.<br><br>CONCLUSION: The results of this study showed that Brazil was severely affected by the COVID-19 pandemic, both in terms of mortality and morbidity. The availability of timely post-pandemic data, as presented in this study, may be highly relevant to inform public policies aimed at promoting healthy behaviors, controlling NCDs, improving mental health care, and supporting specialized care for Long COVID within the public health system.},
}
@article {pmid41286257,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and AlArab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: lung pathophysiology and its relationship with cognitive dysfunction.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {42595},
pmid = {41286257},
issn = {2045-2322},
support = {R01 HL126771/HL/NHLBI NIH HHS/United States ; S10 OD026960/OD/NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; R01 HL169765/HL/NHLBI NIH HHS/United States ; COVID-19 and Emerging Respiratory Viruses Research Award//American Lung Association/ ; NIH NCATS S10OD026960, NIH CTSA program grant UM1TR004403, NIH NHLBI R01HL169765, NIH NHLBI R01HL126771/NH/NIH HHS/United States ; UM1 TR004403/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *COVID-19/physiopathology/complications ; Middle Aged ; *Cognitive Dysfunction/physiopathology/etiology ; *Lung/physiopathology ; Magnetic Resonance Imaging ; Aged ; Post-Acute COVID-19 Syndrome ; Adult ; SARS-CoV-2 ; Respiratory Function Tests ; Anxiety ; Sleep Wake Disorders/physiopathology ; },
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and [129]Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age = 54 ± 11 yrs.; 10 females) that were 32 ± 5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower [129]Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}
@article {pmid40720834,
year = {2025},
author = {Feldman, CH and Santacroce, L and Bassett, IV and Thaweethai, T and Alicic, R and Atchley-Challenner, R and Chung, A and Goldberg, MP and Horowitz, CR and Jacobson, KB and Kelly, JD and Knight, S and Lutrick, K and Mudumbi, P and Parthasarathy, S and Prendergast, H and Quintana, Y and Sharareh, N and Shellito, J and Sherif, ZA and Taylor, BD and Taylor, E and Tsevat, J and Wiley, Z and Williams, NJ and Yee, L and Aponte-Soto, L and Baissary, J and Berry, J and Charney, AW and Costantine, MM and Duven, AM and Erdmann, N and Ernst, KC and Feuerriegel, EM and Flaherman, VJ and Go, M and Hawkins, K and Jacoby, V and John, J and Kelly, S and Kindred, E and Laiyemo, A and Levitan, EB and Levy, BD and Logue, JK and Marathe, JG and Martin, JN and McComsey, GA and Metz, TD and Minor, T and Montgomery, AP and Mullington, JM and Ofotokun, I and Okumura, MJ and Peluso, MJ and Pogreba-Brown, K and Raissy, H and Rosas, JM and Singh, U and VanWagoner, T and Clark, CR and Karlson, EW},
title = {Social Determinants of Health and Risk for Long COVID in the U.S. RECOVER-Adult Cohort.},
journal = {Annals of internal medicine},
volume = {178},
number = {9},
pages = {1287-1297},
pmid = {40720834},
issn = {1539-3704},
support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Social Determinants of Health ; *COVID-19/epidemiology ; Female ; Male ; United States/epidemiology ; Prospective Studies ; Adult ; Middle Aged ; Risk Factors ; SARS-CoV-2 ; Aged ; Poverty ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Social determinants of health (SDoH) contribute to disparities in SARS-CoV-2 infection, but their associations with long COVID are unknown.<br><br>OBJECTIVE: To determine associations between SDoH at the time of SARS-CoV-2 infection and risk for long COVID.<br><br>DESIGN: Prospective observational cohort study.<br><br>SETTING: 33 states plus Washington, DC, and Puerto Rico.<br><br>PARTICIPANTS: Adults (aged &#x2265;18 years) enrolled in RECOVER-Adult (Researching COVID to Enhance Recovery) between October 2021 and November 2023 who were within 30 days of SARS-CoV-2 infection; completed baseline SDoH, comorbidity, and pregnancy questionnaires; and were followed prospectively.<br><br>MEASUREMENTS: Social risk factors from SDoH baseline questionnaires, ZIP code poverty and household crowding measures, and a weighted score of 11 or higher on the Long COVID Research Index 6 months after infection.<br><br>RESULTS: Among 3787 participants, 418 (11%) developed long COVID. After adjustment for demographic characteristics, pregnancy, disability, comorbidities, SARS-CoV-2 severity, and vaccinations, financial hardship (adjusted marginal risk ratio [ARR], 2.36 [95% CI, 1.97 to 2.91]), food insecurity (ARR, 2.36 [CI, 1.83 to 2.98]), less than a college education (ARR, 1.60 [CI, 1.30 to 1.97]), experiences of medical discrimination (ARR, 2.37 [CI, 1.94 to 2.83]), skipped medical care due to cost (ARR, 2.87 [CI, 2.22 to 3.70]), and lack of social support (ARR, 1.79 [CI, 1.50 to 2.17]) were associated with increased risk for long COVID. Living in ZIP codes with the highest (vs. lowest) household crowding was also associated with greater risk (ARR, 1.36 [CI, 1.05 to 1.71]).<br><br>LIMITATION: Selection bias may influence observed associations and generalizability.<br><br>CONCLUSION: Participants with social risk factors at the time of SARS-CoV-2 infection had greater risk for subsequent long COVID than those without. Future studies should determine whether social risk factor interventions mitigate long-term effects of SARS-CoV-2 infection.<br><br>PRIMARY FUNDING SOURCE: National Institutes of Health.},
}
@article {pmid40554463,
year = {2025},
author = {Gross, RS and Thaweethai, T and Salisbury, AL and Kleinman, LC and Mohandas, S and Rhee, KE and Snowden, JN and Tantisira, KG and Warburton, D and Wood, JC and Kinser, PA and Milner, JD and Rosenzweig, EB and Irby, K and Flaherman, VJ and Karlson, EW and Chibnik, LB and Pant, DB and Krishnamoorthy, A and Gallagher, R and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, S and Dreyer, BP and Blancero, F and Carmilani, M and Coombs, K and Fitzgerald, ML and Letts, RJ and Peddie, AK and Aschner, JL and Atz, AM and Banerjee, D and Bogie, A and Bukulmez, H and Clouser, K and Cottrell, LA and Cowan, K and D'Sa, VA and Dozor, A and Elliott, AJ and Faustino, EVS and Fiks, AG and Gaur, S and Gennaro, ML and Gordon, S and Hasan, UN and Hester, CM and Hogan, A and Hsia, DS and Kaelber, DC and Kosut, JS and Krishnan, S and McCulloh, RJ and Michelow, IC and Nolan, SM and Oliveira, CR and Olson, LM and Pace, WD and Palumbo, P and Raissy, H and Reyes, A and Ross, JL and Salazar, JC and Selvarangan, R and Stein, CR and Stevenson, MD and Teufel, RJ and Werzberger, A and Westfall, JM and Zani, K and Zempsky, WT and Zimmerman, E and Bind, MC and Chan, J and Guan, Z and Morse, RE and Reeder, HT and Metz, TD and Newburger, JW and Truong, DT and Foulkes, AS and Stockwell, MS and , and , },
title = {Characterizing Long COVID Symptoms During Early Childhood.},
journal = {JAMA pediatrics},
volume = {179},
number = {7},
pages = {781-792},
pmid = {40554463},
issn = {2168-6211},
support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; },
abstract = {IMPORTANCE: Recent studies have identified characteristic symptom patterns of long COVID (LC) in adults and children older than 5 years. However, LC remains poorly characterized in early childhood. This knowledge gap limits efforts to identify, care for, and prevent LC in this vulnerable population.<br><br>OBJECTIVES: To identify symptoms that had the greatest difference in frequency comparing children with a history of SARS-CoV-2 infection to those without, to identify differences in the types of symptoms by age group (infants/toddlers [0-2 years] vs preschool-aged children [3-5 years]), and to derive an index that can be used in research studies to identify young children with LC.<br><br>This was a multisite longitudinal cohort study with enrollment from over 30 US health care and community settings, including infants, toddlers, and preschool-aged children with and without SARS-CoV-2 infection history. Study data were analyzed from May to December 2024.<br><br>EXPOSURE: SARS-CoV-2 infection.<br><br>MAIN OUTCOMES AND MEASURES: LC and 41 symptoms among infants/toddlers and 75 symptoms among preschool-aged children.<br><br>RESULTS: The study included 472 infants/toddlers (mean [SD] age, 12 [9] months; 278 infected with SARS-CoV-2; 194 uninfected; 234 male [50%]; 73 Black or African American [16%]; 198 Hispanic, Latino, or Spanish [43%]; 242 White [52%]) and 539 preschool-aged children (mean [SD] age, 48 [10] months; 399 infected with SARS-CoV-2; 140 uninfected; 277 female [51%]; 70 Black or African American [13%]; 210 Hispanic, Latino, or Spanish [39%]; 287 White [54%]). The median (IQR) time between first infections and completion of symptom surveys was 318 (198-494) days for infants/toddlers and 520 (330-844) days for preschool-aged children. A research index was derived for each age group based on symptoms most associated with infection history. The index is calculated by summing scores assigned to each prolonged symptom that was present, where higher scores indicate greater magnitude of association with history of SARS-CoV-2 infection: poor appetite (5 points), trouble sleeping (3.5 points), wet cough (3.5 points), dry cough (3 points), and stuffy nose (0.5 points) for infants/toddlers, and daytime tiredness/sleepiness/low energy (6.5 points) and dry cough (3 points) for preschool-aged children. Among infants/toddlers with infection, 40 of 278 (14%) were classified as having probable LC by having an index of at least 4 points. Among preschool-aged children, 61 of 399 (15%) were classified as having probable LC by having an index of at least 3 points. Participants with higher indices often had poorer overall health, lower quality of life, and perceived delays in developmental milestones.<br><br>CONCLUSIONS AND RELEVANCE: This cohort study identified symptom patterns and derived research indices that were distinct between the 2 age groups and differed from those previously identified in older ages, demonstrating the need to characterize LC separately across age ranges.},
}
@article {pmid40210368,
year = {2025},
author = {Verduzco-Gutierrez, M and Fleming, TK and Azola, AM},
title = {Considerations for Long COVID Rehabilitation in Women.},
journal = {Physical medicine and rehabilitation clinics of North America},
volume = {36},
number = {2},
pages = {371-387},
doi = {10.1016/j.pmr.2024.11.009},
pmid = {40210368},
issn = {1558-1381},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sex Factors ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.},
}
@article {pmid39947217,
year = {2025},
author = {Proal, AD and Aleman, S and Bomsel, M and Brodin, P and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Hewitt, SM and Iwasaki, A and Krumholz, HM and Locci, M and Marconi, VC and Mehandru, S and Muller-Trutwin, M and Painter, MM and Pretorius, E and Price, DA and Putrino, D and Qian, Y and Roan, NR and Salmon, D and Tan, GS and VanElzakker, MB and Wherry, EJ and Van Weyenbergh, J and Yonker, LM and Peluso, MJ},
title = {Targeting the SARS-CoV-2 reservoir in long COVID.},
journal = {The Lancet. Infectious diseases},
volume = {25},
number = {5},
pages = {e294-e306},
pmid = {39947217},
issn = {1474-4457},
support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 HL173059/HL/NHLBI NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/virology/complications ; *SARS-CoV-2/physiology/drug effects ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; Clinical Trials as Topic ; },
abstract = {There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.},
}
@article {pmid39489523,
year = {2024},
author = {Holmes, A and Emerson, L and Irving, LB and Tippett, E and Pullin, JM and Young, J and Watters, DA and Hamilton, A},
title = {Persistent symptoms after COVID-19: an Australian stratified random health survey on long COVID.},
journal = {The Medical journal of Australia},
volume = {221 Suppl 9},
number = {},
pages = {S12-S17},
doi = {10.5694/mja2.52473},
pmid = {39489523},
issn = {1326-5377},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Female ; Male ; Middle Aged ; Adult ; *Post-Acute COVID-19 Syndrome ; *Health Surveys ; *SARS-CoV-2 ; Aged ; Quality of Life ; Australia/epidemiology ; Victoria/epidemiology ; Young Adult ; Depression/epidemiology ; Adolescent ; Anxiety/epidemiology ; Fatigue/epidemiology/etiology ; },
abstract = {OBJECTIVE: To determine the impact of persistent symptoms after coronavirus disease 2019 (COVID-19) in an Australian population.<br><br>DESIGN, SETTING, PARTICIPANTS: We conducted a statewide health survey of a stratified random sample of adults who had had a confirmed acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19-positive group) and their close contacts (control group). The sample was drawn from Victoria's COVID-19 database between January 2020 and October 2022. Data were collected from 12&#x2009;688 survey respondents between September 2022 and April 2023 (11&#x2009;174 in the COVID-19-positive group and 1514 in the control group).<br><br>MAIN OUTCOME MEASURES: Persistent new symptoms, recovery, and daily function using validated questionnaires for fatigue, neurocognitive symptoms, anxiety, depression and quality of life.<br><br>RESULTS: At a mean of 12.6 months after infection, 4560 respondents in the COVID-19-positive group (39.1%; 95% CI, 37.9-40.3%) reported at least one persistent new symptom, compared with 216 respondents in the control group (20.8%; 95% CI, 18.5-23.1%). A total of 1656 respondents (14.2%; 95% CI, 13.4-15.0%) were classified as having clinical long COVID using the criteria of at least one persistent new symptom and less than 80% recovery three months after the infection. Of the respondents with clinical long COVID, 535 (3.2%; 95% CI, 2.6-3.8%) reported at least moderate problems with usual activities at 12 months after their infection. The proportion of respondents with clinical long COVID was lower for those with more recent infections. The risk factors for clinical long COVID were female sex, age 40-49 years, infection severity, chronic illness, and past anxiety or depression. Factors associated with a decreased risk of having clinical long COVID included infection when the Omicron strain was dominant and infection when the Delta strain was dominant, as compared with when the ancestral strain of the virus was dominant.<br><br>CONCLUSION: Persistent symptoms after COVID-19 are common, though with a lower incidence following infection from less virulent strains. Although long COVID can be largely managed in primary care, a minority of people who have persistent symptoms and impaired function may require specialist care pathways, the effectiveness of which should be a focus of future research.},
}
@article {pmid38343863,
year = {2025},
author = {Preiss, A and Bhatia, A and Aragon, LV and Baratta, JM and Baskaran, M and Blancero, F and Brannock, MD and Chew, RF and Díaz, I and Fitzgerald, M and Kelly, EP and Zhou, A and Carton, TW and Chute, CG and Haendel, M and Moffitt, R and Pfaff, E},
title = {EFFECT OF PAXLOVID TREATMENT DURING ACUTE COVID-19 ON LONG COVID ONSET: AN EHR-BASED TARGET TRIAL EMULATION FROM THE N3C AND RECOVER CONSORTIA.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38343863},
support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U01 DA055358/DA/NIDA NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. Researchers have begun to explore whether Paxlovid treatment in the acute phase of COVID-19 could help prevent the onset of PASC.<br><br>METHODS AND FINDINGS: We used electronic health records from the National Clinical Cohort Collaborative (N3C) to define a cohort of 410,026 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation framework to estimate the effect of Paxlovid treatment on PASC incidence. The treatment group was defined as outpatients prescribed Paxlovid within five days of COVID-19 index, and the control group was defined as all patients meeting eligibility criteria not in the treatment group. The follow-up period was 180 days. We estimated overall PASC incidence using a computable phenotype. We also measured incident cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment had a small effect on overall PASC incidence (relative risk [RR] 0.94; 95% CI [0.90, 0.99]; p=0.011). It had a slightly stronger protective effect against cognitive (RR 0.86; 95% CI [0.77, 0.95]; p<0.001) and fatigue (RR 0.92; 95% CI [0.86, 0.97]; p=0.002) symptoms.<br><br>CONCLUSIONS: In this study, Paxlovid had a weaker preventative effect on PASC than in prior observational studies, suggesting that Paxlovid is unlikely to become a definitive solution for preventing PASC. Differing effects by symptom cluster suggest that the etiology of cognitive and fatigue symptoms may be more closely related to viral load than that of respiratory symptoms. Future research should explore potential heterogeneous treatment effects across PASC subphenotypes.},
}
@article {pmid36748919,
year = {2023},
author = {Hicks, SD},
title = {Comparison of Symptom Duration Between Children With SARS-CoV-2 and Peers With Other Viral Illnesses During the COVID-19 Pandemic.},
journal = {Clinical pediatrics},
volume = {62},
number = {9},
pages = {1101-1108},
pmid = {36748919},
issn = {1938-2707},
support = {R33 HD105610/HD/NICHD NIH HHS/United States ; R61 HD105610/HD/NICHD NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; },
mesh = {Child ; Humans ; Child, Preschool ; Adolescent ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Cross-Sectional Studies ; Pain ; },
abstract = {Some children and young people (CYP) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience persistent symptoms, commonly called "long COVID." It remains unclear whether symptoms of SARS-CoV-2 persist longer than those of other respiratory viruses, particularly in young children. This cross-sectional study involved 372 CYP (0-15 years) tested for SARS-CoV-2. Character and duration of symptoms (cough, runny nose, sore throat, rash, diarrhea, vomiting, sore muscles, fatigue, fever, loss of smell) were compared between CYP with a positive test (n = 100) and those with a negative test (n = 272), while controlling for medical/demographic covariates. The average duration of symptoms for CYP with a positive SARS-CoV-2 test (8.5 ± 10 days) did not differ from that of CYP with a negative test (7.2 ± 5 days, P = .71, d = 0.046). A positive SARS-CoV-2 test did not increase the risk (36/372, 10%) of symptoms persisting for ≥3 weeks (odds ratio = 0.96, 95% confidence interval = 0.45-2.0). These results suggest CYP with non-SARS-CoV-2 infections experience a similar duration of symptoms as peers with SARS-CoV-2 infection.},
}
@article {pmid35227568,
year = {2022},
author = {Serhan, CN and Libreros, S and Nshimiyimana, R},
title = {E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition.},
journal = {Seminars in immunology},
volume = {59},
number = {},
pages = {101597},
pmid = {35227568},
issn = {1096-3618},
support = {K99 HL153673/HL/NHLBI NIH HHS/United States ; R35 GM139430/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *COVID-19 ; Docosahexaenoic Acids/therapeutic use ; *Eicosapentaenoic Acid/therapeutic use ; Inflammation ; Inflammation Mediators/metabolism ; Metabolome ; Pandemics ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; },
abstract = {The COVID-19 pandemic has raised international awareness of the importance of rigorous scientific evidence and the havoc caused by uncontrolled excessive inflammation. Here we consider the evidence on whether the specialized pro-resolving mediators (SPMs) are ready to meet this challenge as well as targeted metabololipidomics of the resolution-inflammation metabolomes. Specific stereochemical mechanisms in the biosynthesis of SPMs from omega-3 essential fatty acids give rise to unique local-acting lipid mediators. SPMs possess stereochemically defined potent bioactive structures that are high-affinity ligands for cognate G protein-coupled surface receptors that evoke the cellular responses required for efficient resolution of acute inflammation. The SPMs biosynthesized from the major omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are coined Resolvins (resolution phase interaction products; E series and D-series), Protectins and Maresins (macrophage mediators in resolving inflammation). Their biosynthesis and stereochemical assignments are established and confirmed (>1,441 resolvin publications in PubMed.gov) as well as their functional roles on innate immune cells and adaptive immune cells (both lymphocyte T-cell subsets and B-cells). The resolution of a protective acute inflammatory response is governed mainly by phagocytes that actively clear apoptotic cells, debris, blood clots and pathogens. These resolution phase functions of the acute inflammatory response are enhanced by SPMs, which together prepare the inflammatory loci for homeostasis and stimulate tissue regeneration via activating stem cells and the biosynthesis of novel cys-SPMs (e.g. MCTRs, PCTRs and RCTRs). These cys-SPMs also activate regeneration, are organ protective and stimulate resolution of local inflammation. Herein, we review the biosynthesis and functions of the E-series resolvins, namely resolvin E1 (the first n-3 resolvin identified), resolvin E2, resolvin E3 and resolvin E4 biosynthesized from their precursor eicosapentaenoic acid (EPA), and the critical role of total organic synthesis in confirming SPM complete stereochemistry, establishing their potent functions in resolution of inflammation, and novel structures. The physical properties of each biologically derived SPM, i.e., ultra-violet (UV) absorbance, chromatographic behavior, and tandem mass spectrometry (MS[2]) fragmentation, were matched to SPMs biosynthesized and prepared by stereospecific total organic synthesis. We briefly review this approach, also used with the endogenous D-series resolvins, protectins and maresins confirming their potent functions in resolution of inflammation, that paves the way for their rigorous evaluation in human tissues and clinical trials. The assignment of complete stereochemistry for each of the E and D series Resolvins, Protectins and Maresins was a critical and required step that enabled human clinical studies as in SPM profiling in COVID-19 infections and experimental animal disease models that also opened the promise of resolution physiology, resolution pharmacology and targeted precision nutrition as new areas for monitoring health and disease mechanisms.},
}
@article {pmid41795913,
year = {2026},
author = {Thorpe, DW and Jones, LA and Martin, AM and Coleman, RA and Allman, C and Peterson, RA and Keating, DJ},
title = {The role of peripheral serotonin in SARS-CoV-2 infectivity, COVID-19 treatment and long COVID.},
journal = {Immunology and cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imcb.70097},
pmid = {41795913},
issn = {1440-1711},
abstract = {Gastrointestinal symptoms have emerged as a common, but underappreciated, cause of morbidity in relation to SARS-CoV-2 infection and the COVID-19 pandemic. This manifests as a range of indications including diarrhea, anorexia, nausea, vomiting and abdominal pain. In addition, the gastrointestinal tract may represent a route of viral entry via the epithelial cell layer lining the gut wall. This route of entry could be a significant component of disease pathogenesis, including effects on the nervous system via the gut-brain axis. In this review, we provide an assessment of the effects of COVID-19 on the gastrointestinal system, its involvement in disease severity and potential pathways for viral entry and infection in the gastrointestinal tract. We also examine evidence that gut-derived serotonin is affected by SARS-CoV-2 infection, how this may link to symptoms and disease pathogenesis and the potential link to the efficacy of selective serotonin reuptake inhibitors in reducing COVID-19 severity.},
}
@article {pmid41795493,
year = {2026},
author = {Amitani, H and Sakato, T and Asakawa, A},
title = {Resolution of Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome symptoms following kanshoho, a low-pressure muscle relaxation technique: A case report.},
journal = {Explore (New York, N.Y.)},
volume = {22},
number = {3},
pages = {103374},
doi = {10.1016/j.explore.2026.103374},
pmid = {41795493},
issn = {1878-7541},
abstract = {Post-COVID-19 condition (Long COVID) can cause persistent multi-system symptoms such as fatigue, pain, and cognitive dysfunction ("brain fog"), and a subset of patients meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Treatment options remain limited, particularly when post-exertional malaise (PEM) restricts exercise-based rehabilitation. A 41-year-old woman developed refractory symptoms after acute SARS-CoV-2 infection, including severe fatigue, posterior neck and shoulder pain, bilateral upper extremity numbness, brain fog, and insomnia. Despite up-titration of sertraline to 50 mg/day by a previous physician and trials of other symptomatic medications, her symptoms did not show meaningful improvement. After exclusion of alternative organic causes, she was diagnosed with Long COVID and met diagnostic criteria for ME/CFS. Kanshoho, a low-pressure muscle relaxation technique, was administered as the primary intervention, with brief advice on activity pacing; sertraline (50 mg/day) was continued initially and later tapered at the patient's request, without clear symptom worsening, and subsequently discontinued. After 10 sessions over 2.5 months, all symptoms resolved at the final assessment. Fatigue visual analog scale (VAS) improved from 79 mm to 0 mm, performance status improved from 7 to 0, and the Profile of Mood States, Second Edition Total Mood Disturbance raw score decreased from 136 to -19. Although causality cannot be inferred from a single case, this low-load approach may warrant evaluation in controlled studies, especially for patients in whom PEM limits conventional rehabilitation.},
}
@article {pmid41754151,
year = {2026},
author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I and Dimian, M and Mangul, S},
title = {Vitamin D in Infectious Diseases: A Narrative Review Focusing on COVID-19, Long COVID, and Influenza.},
journal = {Nutrients},
volume = {18},
number = {4},
pages = {},
pmid = {41754151},
issn = {2072-6643},
mesh = {Humans ; *Vitamin D/therapeutic use/blood/administration &amp; dosage/analogs &amp; derivatives ; *COVID-19/immunology/complications ; *Influenza, Human/immunology/drug therapy ; *Vitamin D Deficiency/immunology/complications/drug therapy ; Dietary Supplements ; SARS-CoV-2 ; Immunity, Innate/drug effects ; Vitamins ; },
abstract = {Vitamin D is a secosteroid hormone traditionally recognized for its role in bone and mineral metabolism, but it is increasingly understood to also function as an important immunomodulator influencing susceptibility to and outcomes of infectious diseases. This narrative review summarizes current evidence on the immunological, clinical, and preventive effects of vitamin D in the context of novel coronavirus disease (COVID-19), post-acute sequelae of SARS-CoV-2 infection (long COVID), and influenza. Mechanistically, vitamin D enhances innate immune defenses through the induction of antimicrobial peptides, including cathelicidin and defensins, and modulates adaptive immunity by suppressing maladaptive Th1/Th17 responses while promoting regulatory T-cell activity. Observational studies have frequently associated vitamin D deficiency with more severe COVID-19 outcomes; however, these associations may be influenced by confounding factors and reverse causality. Some meta-analyses suggest that vitamin D supplementation reduced rates of intensive care unit admission and ventilatory support, particularly among older adults and individuals with low baseline serum 25-hydroxyvitamin D concentrations. Emerging evidence also indicates that inadequate vitamin D status may be associated with an increased risk and symptom burden of long COVID, although causality has not been established. In the case of influenza, a limited number of randomized controlled trials (RCTs) and meta-analyses report a modest but statistically significant reduction in infection risk, especially with daily or weekly vitamin D supplementation in populations with low baseline vitamin D levels. Clinical guidelines consistently recommend maintaining adequate vitamin D status for general health but do not endorse high-dose vitamin D as a treatment for COVID-19 due to inconsistent trial findings. Overall, vitamin D should not be considered a standalone therapeutic agent; rather, maintaining sufficient vitamin D levels represents a low-risk, potentially beneficial strategy to support immune resilience against respiratory viral infections.},
}
@article {pmid41532554,
year = {2026},
author = {Liao, TL and Liu, PY and Chen, YM and Tang, KT and Liu, HJ and Chen, DY},
title = {Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {13},
number = {13},
pages = {e08695},
pmid = {41532554},
issn = {2198-3844},
support = {NSTC 112-2314-B-075A-002-MY3//National Science and Technology Council/ ; TCVGH-1137305C//Taichung Veterans General Hospital/ ; TCVGH-1133902E//Taichung Veterans General Hospital/ ; TCVGH-1143918C//Taichung Veterans General Hospital/ ; },
mesh = {*COVID-19/immunology/metabolism/pathology ; *Neutrophils/metabolism/immunology ; Humans ; Animals ; *Extracellular Vesicles/metabolism ; *Inflammation/metabolism/immunology ; Extracellular Traps/metabolism/immunology ; SARS-CoV-2 ; Male ; rab GTP-Binding Proteins/metabolism ; *Autophagy ; rab7 GTP-Binding Proteins ; Female ; Toll-Like Receptor 8/metabolism ; Middle Aged ; TOR Serine-Threonine Kinases/metabolism ; Signal Transduction ; Disease Models, Animal ; },
abstract = {Immunometabolism and neutrophil extracellular traps (NETs) play pivotal roles in the pathogenesis of coronavirus disease 2019 (COVID-19) and its postacute sequelae. However, the upstream regulators that reprogram neutrophil lipid metabolism and trigger excessive NET formation remain largely undefined. This study identifies a transfer RNA-derived fragment, tRF-His-GTG-1, enriched in platelet-derived extracellular vesicles, as a key driver of neutrophil lipophagy dysfunction and inflammation in COVID-19. The use on neutrophils from 60 patients and 20 healthy controls, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamster model, and multiple in vitro assays shows that severe COVID-19 and long COVID are characterized by increased lipid droplet (LD) accumulation and NET release. Mechanistically, tRF-His-GTG-1 activates Toll-like receptor 8 (TLR8)-mammalian target of rapamycin (mTOR) signaling and suppresses RAB7A expression, changes that impair lipophagic flux. This dual pathway impairs lipophagy and promotes NET formation and proinflammatory cytokine secretion. Importantly, ex vivo treatment with a tRF-His-GTG-1 inhibitor restores lipophagy, reduces LD and NET levels, and suppresses interleukin 1beta (IL-1β)/IL-8 production in patient-derived neutrophils. These findings reveal a novel EV-mediated immunometabolic axis linking platelets to neutrophil dysfunction, and position tRF-His-GTG-1 as a promising RNA-based therapeutic target for COVID-19-associated hyperinflammation.},
}
@article {pmid41396732,
year = {2026},
author = {Asghar, AF and Enderle, J and Salazar, JH and Esani, M},
title = {Predictors of post-acute sequelae of coronavirus disease 2019 and long COVID in adults and children: a retrospective cohort study using us electronic health record data.},
journal = {Journal of public health (Oxford, England)},
volume = {48},
number = {1},
pages = {185-194},
doi = {10.1093/pubmed/fdaf157},
pmid = {41396732},
issn = {1741-3850},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Retrospective Studies ; Male ; Female ; Child ; Adult ; Electronic Health Records/statistics &amp; numerical data ; Middle Aged ; Adolescent ; United States/epidemiology ; Child, Preschool ; Young Adult ; SARS-CoV-2 ; Risk Factors ; Infant ; Post-Acute COVID-19 Syndrome ; Aged ; Comorbidity ; Incidence ; },
abstract = {OBJECTIVE: This study examined the incidence and predictors of post-acute sequelae of COVID-19 (PASC) and Long COVID in adults and children with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Associations assessed included demographic factors, comorbidities, lab markers, and patient clinical complications.<br><br>METHOD: A retrospective cohort of 13,940 patients with confirmed SARS-CoV-2 infection (7836 adults and 6104 children) from the Optum&#xae; COVID-19 Electronic Health Record dataset was analyzed (1 June 2020-30 June 2021). PASC was defined as symptoms lasting <3&#xa0;months postinfection and Long COVID as symptoms &#x2265;3&#xa0;months. Inclusion criteria were patients of all ages with a confirmed SARS-CoV-2 infection. Excluded from the study were patients in the Texas Department of Criminal Justice system and patients with active HIV, malignancy, or respiratory viral/bacterial infection. Statistical analyses (chi-square, Mann-Whitney U, multivariable logistic regression) were performed using Microsoft Excel and IBM Statistical Package for the Social Sciences statistics V.25.<br><br>RESULTS: Symptoms consistent with PASC were reported by 21.5% of adult patients, with 8.8% reporting Long COVID; 10.5% of pediatric patients reported PASC, with 9% reporting Long COVID (P&#xa0;<&#xa0;.05). In adults, predictors of PASC included age &#x2265;54, female sex, non-Caucasian race, smoking, obesity, pneumonia, and multiple comorbidities; higher red blood cell count was protective. Predictors of Long COVID in adults was associated with female sex, obesity, and heart disease. In children, predictors of PASC included female sex and comorbidities. Younger age (&#x2264;10&#xa0;years) was a significant predictor of Long COVID in children.<br><br>Protocols that include targeted follow-up and early intervention are needed for post-COVID conditions in high-risk individuals across age groups. Integrating predictive markers into routine care could enhance preparedness and resilience against future waves of post-viral syndromes.},
}
@article {pmid39804551,
year = {2025},
author = {Vernon, SD and Zheng, T and Do, H and Marconi, VC and Jason, LA and Singer, NG and Natelson, BH and Sherif, ZA and Bonilla, HF and Taylor, E and Mullington, JM and Ashktorab, H and Laiyemo, AO and Brim, H and Patterson, TF and Akintonwa, TT and Sekar, A and Peluso, MJ and Maniar, N and Bateman, L and Horwitz, LI and Hess, R and , },
title = {Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study.},
journal = {Journal of general internal medicine},
volume = {40},
number = {5},
pages = {1085-1094},
pmid = {39804551},
issn = {1525-1497},
support = {P30 AI050409/AI/NIAID NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; OTA OT2HL161841/HL/NHLBI NIH HHS/United States ; OT2HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Female ; Incidence ; Male ; Adult ; Middle Aged ; Prevalence ; Longitudinal Studies ; *Fatigue Syndrome, Chronic/epidemiology/diagnosis/etiology ; United States/epidemiology ; Cohort Studies ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may occur after infection. How often people develop ME/CFS after SARS-CoV-2 infection is unknown.<br><br>OBJECTIVE: To determine the incidence and prevalence of post-COVID-19 ME/CFS among adults enrolled in the Researching COVID to Enhance Recovery (RECOVER-Adult) study.<br><br>RECOVER-Adult is a longitudinal observational cohort study conducted across the U.S. We included participants who had a study visit at least 6 months after infection and had no pre-existing ME/CFS, grouped as (1) acute infected, enrolled within 30 days of infection or enrolled as uninfected who became infected (n=4515); (2) post-acute infected, enrolled greater than 30 days after infection (n=7270); and (3) uninfected (1439).<br><br>MEASUREMENTS: Incidence rate and prevalence of post-COVID-19 ME/CFS based on the 2015 Institute of Medicine ME/CFS clinical diagnostic criteria.<br><br>RESULTS: The incidence rate of ME/CFS in participants followed from time of SARS-CoV-2 infection was 2.66 (95% CI 2.63-2.70) per 100 person-years while the rate in matched uninfected participants was 0.93 (95% CI 0.91-10.95) per 100 person-years: a hazard ratio of 4.93 (95% CI 3.62-6.71). The proportion of all RECOVER-Adult participants that met criteria for ME/CFS following SARS-CoV-2 infection was 4.5% (531 of 11,785) compared to 0.6% (9 of 1439) in uninfected participants. Post-exertional malaise was the most common ME/CFS symptom in infected participants (24.0%, 2830 of 11,785). Most participants with post-COVID-19 ME/CFS also met RECOVER criteria for long COVID (88.7%, 471 of 531).<br><br>LIMITATIONS: The ME/CFS clinical diagnostic criteria uses self-reported symptoms. Symptoms can wax and wane.<br><br>CONCLUSION: ME/CFS is a diagnosable sequela that develops at an increased rate following SARS-CoV-2 infection. RECOVER provides an unprecedented opportunity to study post-COVID-19 ME/CFS.},
}
@article {pmid39693079,
year = {2025},
author = {Geng, LN and Erlandson, KM and Hornig, M and Letts, R and Selvaggi, C and Ashktorab, H and Atieh, O and Bartram, L and Brim, H and Brosnahan, SB and Brown, J and Castro, M and Charney, A and Chen, P and Deeks, SG and Erdmann, N and Flaherman, VJ and Ghamloush, MA and Goepfert, P and Goldman, JD and Han, JE and Hess, R and Hirshberg, E and Hoover, SE and Katz, SD and Kelly, JD and Klein, JD and Krishnan, JA and Lee-Iannotti, J and Levitan, EB and Marconi, VC and Metz, TD and Modes, ME and Nikolich, J&#x17d; and Novak, RM and Ofotokun, I and Okumura, MJ and Parthasarathy, S and Patterson, TF and Peluso, MJ and Poppas, A and Quintero Cardona, O and Scott, J and Shellito, J and Sherif, ZA and Singer, NG and Taylor, BS and Thaweethai, T and Verduzco-Gutierrez, M and Wisnivesky, J and McComsey, GA and Horwitz, LI and Foulkes, AS and , },
title = {2024 Update of the RECOVER-Adult Long COVID Research Index.},
journal = {JAMA},
volume = {333},
number = {8},
pages = {694-700},
pmid = {39693079},
issn = {1538-3598},
support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; R21 DC021054/DC/NIDCD NIH HHS/United States ; R01 HL151508/HL/NHLBI NIH HHS/United States ; R01 DC013277/DC/NIDCD NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 DC017397/DC/NIDCD NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; F31 DC006764/DC/NIDCD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; R03 DC010267/DC/NIDCD NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome/classification/complications/diagnosis/virology ; Prospective Studies ; Puerto Rico ; SARS-CoV-2/pathogenicity ; United States ; Quality of Life ; },
abstract = {IMPORTANCE: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves.<br><br>OBJECTIVE: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities.<br><br>Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024.<br><br>EXPOSURE: SARS-CoV-2 infection.<br><br>MAIN OUTCOMES AND MEASURES: Presence of LC and participant-reported symptoms.<br><br>RESULTS: A total of 13&#x202f;647 participants (11&#x202f;743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures.<br><br>CONCLUSIONS AND RELEVANCE: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.},
}
@article {pmid39402206,
year = {2024},
author = {Thomas, D and Noishiki, C and Gaddam, S and Wu, D and Manhas, A and Liu, Y and Tripathi, D and Kathale, N and Adkar, SS and Garhyan, J and Liu, C and Xu, B and Ross, EG and Dalman, RL and Wang, KC and Oro, AE and Sallam, K and Lee, JT and Wu, JC and Sayed, N},
title = {CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID.},
journal = {Nature cardiovascular research},
volume = {3},
number = {10},
pages = {1249-1265},
pmid = {39402206},
issn = {2731-0590},
support = {K99 HL163443-01//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 869015//American Heart Association (American Heart Association, Inc.)/ ; R01 HL161002/HL/NHLBI NIH HHS/United States ; R01 AR054780/AR/NIAMS NIH HHS/United States ; K01 HL135455/HL/NHLBI NIH HHS/United States ; R01 HL150693/HL/NHLBI NIH HHS/United States ; R01 AR073170/AR/NIAMS NIH HHS/United States ; K99 HL163443/HL/NHLBI NIH HHS/United States ; R01 HL141851/HL/NHLBI NIH HHS/United States ; R01 HL158641/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/metabolism/complications ; Animals ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; *Chemokine CCL2/metabolism/genetics ; *SARS-CoV-2 ; *Endothelial Cells/metabolism/virology/pathology ; Mice, Transgenic ; Mice ; Male ; Female ; Induced Pluripotent Stem Cells/metabolism ; Oxidative Stress ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Aged ; Myocytes, Cardiac/metabolism/virology/pathology ; Organoids/metabolism ; Spike Glycoprotein, Coronavirus/metabolism/genetics ; Heart Diseases/metabolism/pathology/virology/etiology ; },
abstract = {Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.},
}
@article {pmid39196964,
year = {2024},
author = {Gross, RS and Thaweethai, T and Kleinman, LC and Snowden, JN and Rosenzweig, EB and Milner, JD and Tantisira, KG and Rhee, KE and Jernigan, TL and Kinser, PA and Salisbury, AL and Warburton, D and Mohandas, S and Wood, JC and Newburger, JW and Truong, DT and Flaherman, VJ and Metz, TD and Karlson, EW and Chibnik, LB and Pant, DB and Krishnamoorthy, A and Gallagher, R and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, S and Dreyer, BP and Carmilani, M and Coombs, K and Fitzgerald, ML and Güthe, N and Hornig, M and Letts, RJ and Peddie, AK and Taylor, BD and Balaraman, V and Bogie, A and Bukulmez, H and Dozor, AJ and Eckrich, D and Elliott, AJ and Evans, DN and Farkas, JS and Faustino, EVS and Fischer, L and Gaur, S and Harahsheh, AS and Hasan, UN and Hsia, DS and Huerta-Montañez, G and Hummel, KD and Kadish, MP and Kaelber, DC and Krishnan, S and Kosut, JS and Larrabee, J and Lim, PPC and Michelow, IC and Oliveira, CR and Raissy, H and Rosario-Pabon, Z and Ross, JL and Sato, AI and Stevenson, MD and Talavera-Barber, MM and Teufel, RJ and Weakley, KE and Zimmerman, E and Bind, MC and Chan, J and Guan, Z and Morse, RE and Reeder, HT and Akshoomoff, N and Aschner, JL and Bhattacharjee, R and Cottrell, LA and Cowan, K and D'Sa, VA and Fiks, AG and Gennaro, ML and Irby, K and Khare, M and Guttierrez, JL and McCulloh, RJ and Narang, S and Ness-Cochinwala, M and Nolan, S and Palumbo, P and Ryu, J and Salazar, JC and Selvarangan, R and Stein, CR and Werzberger, A and Zempsky, WT and Aupperle, R and Baker, FC and Banich, MT and Barch, DM and Baskin-Sommers, A and Bjork, JM and Bookheimer, SY and Brown, SA and Casey, BJ and Chang, L and Clark, DB and Dale, AM and Dapretto, M and Ernst, TM and Fair, DA and Feldstein Ewing, SW and Foxe, JJ and Freedman, EG and Friedman, NP and Garavan, H and Gee, DG and Gonzalez, R and Gray, KM and Heitzeg, MM and Herting, MM and Jacobus, J and Laird, AR and Larson, CL and Lisdahl, KM and Luciana, M and Luna, B and Madden, PAF and McGlade, EC and Müller-Oehring, EM and Nagel, BJ and Neale, MC and Paulus, MP and Potter, AS and Renshaw, PF and Sowell, ER and Squeglia, LM and Tapert, S and Uddin, LQ and Wilson, S and Yurgelun-Todd, DA and Foulkes, AS and Stockwell, MS and , and , },
title = {Characterizing Long COVID in Children and Adolescents.},
journal = {JAMA},
volume = {332},
number = {14},
pages = {1174-1188},
pmid = {39196964},
issn = {1538-3598},
support = {U24 DA041147/DA/NIDA NIH HHS/United States ; U01 DA041120/DA/NIDA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; K23 AI159518/AI/NIAID NIH HHS/United States ; U01 DA041156/DA/NIDA NIH HHS/United States ; R01 DA057567/DA/NIDA NIH HHS/United States ; U01 DA041117/DA/NIDA NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; },
abstract = {IMPORTANCE: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.<br><br>OBJECTIVE: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.<br><br>Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.<br><br>EXPOSURE: SARS-CoV-2 infection.<br><br>MAIN OUTCOMES AND MEASURES: PASC and 89 prolonged symptoms across 9 symptom domains.<br><br>RESULTS: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.<br><br>CONCLUSIONS AND RELEVANCE: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.},
}
@article {pmid38630952,
year = {2024},
author = {McAlpine, L and Zubair, AS and Joseph, P and Spudich, S},
title = {Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.},
journal = {Neurology(R) neuroimmunology &amp; neuroinflammation},
volume = {11},
number = {3},
pages = {e200244},
pmid = {38630952},
issn = {2332-7812},
support = {K23 NS133488/NS/NINDS NIH HHS/United States ; L30 NS139301/NS/NINDS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; Middle Aged ; Male ; *Small Fiber Neuropathy ; Case-Control Studies ; Retrospective Studies ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; Immunoglobulins, Intravenous ; *COVID-19 ; *Autonomic Nervous System Diseases ; },
abstract = {OBJECTIVES: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.<br><br>METHODS: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.<br><br>RESULTS: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02).<br><br>DISCUSSION: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.<br><br>CLASSIFICATION OF EVIDENCE: This study provides Class III evidence. It is a retrospective cohort study.},
}
@article {pmid37748514,
year = {2023},
author = {Klein, J and Wood, J and Jaycox, JR and Dhodapkar, RM and Lu, P and Gehlhausen, JR and Tabachnikova, A and Greene, K and Tabacof, L and Malik, AA and Silva Monteiro, V and Silva, J and Kamath, K and Zhang, M and Dhal, A and Ott, IM and Valle, G and Peña-Hernández, M and Mao, T and Bhattacharjee, B and Takahashi, T and Lucas, C and Song, E and McCarthy, D and Breyman, E and Tosto-Mancuso, J and Dai, Y and Perotti, E and Akduman, K and Tzeng, TJ and Xu, L and Geraghty, AC and Monje, M and Yildirim, I and Shon, J and Medzhitov, R and Lutchmansingh, D and Possick, JD and Kaminski, N and Omer, SB and Krumholz, HM and Guan, L and Dela Cruz, CS and van Dijk, D and Ring, AM and Putrino, D and Iwasaki, A},
title = {Distinguishing features of long COVID identified through immune profiling.},
journal = {Nature},
volume = {623},
number = {7985},
pages = {139-148},
pmid = {37748514},
issn = {1476-4687},
support = {R35 GM143072/GM/NIGMS NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; U01 FD005938/FD/FDA HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; T32 GM136651/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Antibodies, Viral/blood/immunology ; Biomarkers/blood ; Cross-Sectional Studies ; *Herpesvirus 4, Human/immunology ; *Hydrocortisone/blood ; Immunophenotyping ; *Lymphocytes/immunology ; Machine Learning ; *Myeloid Cells/immunology ; *Post-Acute COVID-19 Syndrome/diagnosis/immunology/physiopathology/virology ; *SARS-CoV-2/immunology ; },
abstract = {Post-acute infection syndromes may develop after acute viral disease[1]. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions[2-4]. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.},
}
@article {pmid37667052,
year = {2023},
author = {Proal, AD and VanElzakker, MB and Aleman, S and Bach, K and Boribong, BP and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Eimer, W and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Iwasaki, A and Izquierdo-Garcia, D and Locci, M and Mehandru, S and Painter, MM and Peluso, MJ and Pretorius, E and Price, DA and Putrino, D and Scheuermann, RH and Tan, GS and Tanzi, RE and VanBrocklin, HF and Yonker, LM and Wherry, EJ},
title = {SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).},
journal = {Nature immunology},
volume = {24},
number = {10},
pages = {1616-1627},
pmid = {37667052},
issn = {1529-2916},
support = {K08 HL143183/HL/NHLBI NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; R01 HL173059/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; RNA, Viral/genetics ; SARS-CoV-2 ; Antiviral Agents ; Disease Progression ; },
abstract = {Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.},
}
@article {pmid41791802,
year = {2026},
author = {Morsa, M and Dothée, L and Cabello, C and Lesoinne, A and Collette, F and Willems, S},
title = {Psychoeducational interventions for patients with Long COVID and neuropsychological difficulties: A qualitative process evaluation of the COVCOG clinical trial.},
journal = {Neuropsychological rehabilitation},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/09602011.2026.2640067},
pmid = {41791802},
issn = {1464-0694},
abstract = {Between 2022 and 2024, the COVCOG randomized controlled trial evaluated two psychoeducation interventions for people living with Long COVID: one addressing cognitive difficulties and the other affective difficulties. While the results showed small to moderate improvements in both groups, we still lack information on the individual and contextual mechanisms that facilitated or hindered the benefits of the intervention. Our research aimed to understand how, under what circumstances, and for whom the intervention generates changes. A qualitative process evaluation was conducted with patients and clinicians involved in COVCOG. Semi-structured individual interviews were conducted and analysed through reflexive thematic analysis. Sixteen patients and ten clinicians participated. Five themes were developed, helping to better understand the conditions for intervention success: Being recognized as a person with Long COVID, Learning to manage Long COVID on a daily basis, Changing as a person, Considering life after the intervention, and Adapting the clinical protocol. Our findings highlight the importance of both institutional and interpersonal recognition as a foundational mechanism for engagement and perceived effectiveness. Psychoeducation for people living with Long COVID should be designed as part of a broader, adaptive, and evolving care pathway, by supporting patients in navigating its biographical and functional consequences over time.},
}
@article {pmid41791507,
year = {2026},
author = {Cintron, SA and Diaz, FJ and Krebill, R and Hitchcock, SR and Kasuske, L and Yang, FM and Pierce, J},
title = {Prevalence and Symptoms of Post-COVID-19 Syndrome in Active-Duty Military Personnel.},
journal = {The American journal of the medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjms.2026.03.001},
pmid = {41791507},
issn = {1538-2990},
abstract = {BACKGROUND: Post-acute COVID-19 is a syndrome characterized by the persistence of clinical symptoms beyond 4 weeks from the onset of acute symptoms. Over 250,000 Department of Defense service members have recovered or are recovering from acute COVID-19, and the range of symptoms and physiological changes can impact the medical readiness of military service members. Understanding the chronic illness among some of the active-duty personnel with this virus is needed to begin finding treatments to reduce their symptoms and improve their health outcomes.<br><br>METHODS: This was a longitudinal, descriptive study designed to examine the prevalence and persistence of the symptoms of active-duty military persons who have post-COVID-19 syndrome. We obtained data from electronic health records (EHRs) of clinics and hospitals of the armed services from U.S. military bases. The de-identified data set came from the Department of Defense Military Health System Data Repository (MDR) which is a centralized data repository established to capture, archive, validate, integrate, and distribute Defense Health Agency (DHA) data worldwide.<br><br>RESULTS: The most prevalent symptom was pulmonary related, affecting 22.4% of individuals with post-COVID-19 syndrome. The second most prevalent symptom was neurological problems (14.6%), followed by fatigue (13.5%), digestive issues (12.5%), and fever (11.5%). Approximately 3.7% of military personnel with post-COVID-19 experienced cognitive symptoms however, they had the greatest persistence, followed by pulmonary related, fatigue, and neurological symptoms.<br><br>CONCLUSIONS: Based on the symptoms identified, finding treatments for post-COVID-19 syndrome is needed particularly for military personnel to maintain fitness and readiness.},
}
@article {pmid41790803,
year = {2026},
author = {Silva, IVTC and Inoue, LH and Brito, FAM and Baccon, WC and Pesce, GB and Höring, CF and Theodoro, MDS and Inoue, DCME and Dores, LS and Batista, NA and Charlo, PB and Baldissera, VDA and Moura, DRO and Salci, MA and Carreira, L},
title = {Prevalence and factors associated with long Covid in older people in the State of Paraná.},
journal = {Revista da Escola de Enfermagem da U S P},
volume = {60},
number = {},
pages = {e20240429},
doi = {10.1590/1980-220X-REEUSP-2024-0429en},
pmid = {41790803},
issn = {1980-220X},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/complications ; Cross-Sectional Studies ; Aged ; Male ; Female ; Aged, 80 and over ; Prevalence ; Middle Aged ; Risk Factors ; Polypharmacy ; Smoking/epidemiology ; Time Factors ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVE: To analyze the factors associated with long Covid in older people 18 months after the acute phase of the disease.<br><br>METHOD: This cross-sectional and analytical study was conducted with older individuals who had Covid-19 in 2020 and survived the disease in the state of Paran&#xe1;, Brazil. Sociodemographic, lifestyle habits, health and treatment information, as well as information on signs, symptoms and sequelae of the disease were collected through telephone interviews conducted 18 months after notification or hospital discharge. For the analyses, descriptive measures, association tests, and Poisson regression models with robust variance were used.<br><br>RESULTS: Of the 345 older people who participated in the study, 224 (65%) still had some symptom or sequelae of Covid-19 18 months after the illness. Being a smoker or former smoker (PR = 2.21; 95% CI = 1.06;3.36), self-reported sleep quality (PR = 0.32; 95% CI = 0.16-0.47), and the use of continuous medication (RP = 5.24; 95% CI = 2.64-7.85; p < 0.0001) were associated with long-term Covid.<br><br>CONCLUSION: Morbidity and polypharmacy rates are high in this population, contributing to the persistence of symptoms. In this context, it becomes essential to align health services, together with professionals, to meet the needs arising from the sequelae in older people.},
}
@article {pmid41790576,
year = {2026},
author = {Morcos, ZL and Theoharides, TC},
title = {Long COVID neuropathy: The role of mast cells.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag016},
pmid = {41790576},
issn = {1554-6578},
abstract = {Postacute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is estimated to affect over 60 million individuals globally, with almost half of COVID-19 survivors experiencing persistent symptoms such as neuropathic pain, fatigue, and autonomic dysfunction. Despite its prevalence, the pathophysiology of PASC remains poorly understood. This narrative review highlights activation of mast cells (MCs), the unique tissue immune cells as a central contributor to neuropathic manifestations in PASC. Mast cell locations near nerves and vessels allows them to regulate neuroimmune and neurovascular processes. Mast cell activation mirrors patterns seen in small-fiber neuropathy and myalgic encephalomyelitis/chronic fatigue syndrome, suggesting a shared immune-mediated etiology. The SARS-CoV-2 spike protein has been shown to activate MCs via angiotensin-converting enzyme 2 and toll-like receptor 4, triggering release of pro-inflammatory and neurotoxic mediators, including interleukin-1β, interleukin-6, tumor necrosis factor alpha, histamine, and tryptase. Such mediators sensitize peripheral nerves, disrupt the blood-brain barrier, and recruit microglia, ultimately contributing to small-fiber injury, neuroinflammation, and dysautonomia. Emerging reports suggest benefit from MC-directed treatments although responses remain variable. Understanding the role of MCs in PASC may offer a plausible mechanism of pathogenesis and guide targeted therapies. Future studies are needed to validate these findings and improve PASC patient outcomes.},
}
@article {pmid41790479,
year = {2026},
author = {Al-Jassas, HK and Al-Hakeim, HK},
title = {The Principal Component of the Inflammatory Biomarkers is the Best Predictor of Neuropsychiatric Disorders in Long COVID Patients.},
journal = {Clinical neuropharmacology},
volume = {},
number = {},
pages = {},
pmid = {41790479},
issn = {1537-162X},
abstract = {OBJECTIVES: Long COVID (LC) is associated with neuropsychiatric disorders (anxiety, depression, and fatigue), an insulin resistance (IR) state, and inflammatory biomarkers. In the present study, IR and inflammatory biomarkers were used to predict the scores of neuropsychiatric disorders.<br><br>METHODS: The ELISA method was used for measurements of IL-1&#x3b2;, IL-10, IL-18, C-reactive protein (CRP), and insulin in the sera of LC and control subjects. Glucose levels were measured spectrophotometrically. The Hamilton scale for anxiety (HAMA) and depression (HAMD), and the fibro fatigue scale (FFtotal) were used for scoring the neuropsychiatric symptoms. The homeostatic model assessment 2 (HOMA2) calculator was used for computing IR (HOMA2IR), insulin sensitivity (HOMA%S), and pancreatic &#x3b2;-cell function (HOMA%B).<br><br>RESULTS: LC is associated with neuropsychiatric diseases (FFtotal, HAMAtotal, and HAMDtotal), insulin resistance biomarkers, and inflammatory biomarkers. These biomarkers are correlated with each other in LC patients. The building of principal components for inflammatory biomarkers (PC_Inflam) and insulin resistance (PC_IR) creates vectors that could surpass individual biomarkers in neuropsychiatric issue prediction in liver cirrhosis patients. Out of the biomarkers investigated, PC_Inflam is the most important predictor for FFtotal (sensitivity and specificity of 71.4%), HAMAtotal (sensitivity and specificity of 70%), and HAMDtotal (sensitivity of 71.2% and specificity of 71.5%).<br><br>CONCLUSIONS: Neuropsychiatric disorders can be predicted by the principal component built from inflammatory biomarkers (IL-1&#x3b2;, IL-10, IL-18, and CRP). In contrast, PC_IR has a lower predictive value for the neuropsychiatric disorders compared with PC_Inflam. These results indicated the significant role of inflammation in the main symptoms of LC.},
}
@article {pmid41789716,
year = {2026},
author = {Zimmerman, KO and Whitley, R and O'Brien, S and Walt, DR and Levy, BD and Maughan, C and Cerda, M and Olson, R and Bateman, L and Shibao, CA and Make, B and Knopman, D and Redline, S and Jason, LA and Suthar, MS and Low, P and Nolen, TL and Reist, C and Berdan, L and Baden, LR},
title = {Developing a platform protocol for clinical trials evaluating interventions that target proposed mechanisms of Long COVID: RECOVER-VITAL.},
journal = {Clinical trials (London, England)},
volume = {},
number = {},
pages = {17407745261422437},
doi = {10.1177/17407745261422437},
pmid = {41789716},
issn = {1740-7753},
abstract = {BACKGROUND: Long COVID, the chronic sequela of SARS-CoV-2 infection, has affected millions of people worldwide. However, its pathogenesis and treatment remain unknown. To address this critical gap, the National Institutes of Health (NIH) developed the Researching COVID to Enhance Recovery (RECOVER) Initiative that included the Viral Persistence and Reactivation, and Immune Dysregulation (RECOVER-VITAL) study as one of the first of five NIH-sponsored, integrated platform protocols to support the rigorous and rapid investigation of potential interventions for Long COVID.<br><br>METHODS: Experts across academia, the NIH, and the community of patients and caregivers were brought together to design the RECOVER-VITAL protocol. We present the challenges and rationale underpinning critical components of this protocol and provide evidence for use of the platform for efficient execution of current and future Long COVID clinical trials. Facets of the RECOVER-VITAL protocol, including inclusion criteria, intervention groups, study procedures, investigation of biomarkers, and endpoints, were carefully crafted to advance the current and future science and operations of Long COVID clinical trials, particularly in the absence of existing data. The initial trial within the RECOVER-VITAL platform evaluated two durations of an antiviral drug, nirmatrelvir/ritonavir, to test the proposed etiology of viral persistence on the Long COVID symptom clusters of autonomic dysfunction, cognitive dysfunction, and exercise intolerance. The primary outcome measures were patient-reported, and secondary outcomes included performance-based measures for each of the symptom clusters of interest.<br><br>CONCLUSIONS: The RECOVER-VITAL platform protocol has substantial implications for the design and conduct of future Long COVID clinical trials.},
}
@article {pmid41785725,
year = {2026},
author = {Ono, R and Arita, R and Takayama, S and Kikuchi, A and Akaishi, C and Ishii, T},
title = {Integrative strategy for Long COVID neuropsychiatric symptoms: A case report on Kamikihito and Bupleurum-Scutellaria formulas guided by pharmacological rationale.},
journal = {Explore (New York, N.Y.)},
volume = {22},
number = {3},
pages = {103353},
doi = {10.1016/j.explore.2026.103353},
pmid = {41785725},
issn = {1878-7541},
abstract = {Brain fog is a refractory symptom of Long COVID lacking established standard treatments. We present a case of a male in his fifties who developed persistent brain fog, fatigue, and anxiety five months post-COVID-19. Baseline assessments revealed significant impairment in quality of life (The EuroQol 5 dimensions 5 levels [EQ-5D-5L]: health-related QOL [HR-QOL] 0.696, EQ-visual analogue scale [VAS]: 50, and 12-Item Short-Form Health Survey [SF-12] Mental Component Summary [MCS]: 38.5, Role/Social Component Summary .[RCS]: 34.6) and high psychological distress (the Self-rating Depression Scale [SDS]: 50, the State-Trait Anxiety Inventory [STAI]-state/trait: 60/49). We employed an integrative therapeutic strategy combining diagnosis based on Japanese traditional medicine (Kampo medicine) with modern pharmacological rationale. Initially, Kamikihito was prescribed to alleviate anxiety and support neurogenesis. Subsequently, considering the mechanism of neuroinflammation, Saireito and Saikokaryukotsuboreito-formulas containing Scutellaria root and Bupleurum root-may be added to suppress microglial activation. Following this regimen, symptoms were alleviated, enabling a return to work within 2.5 months. At three months, marked improvements were observed (EQ-5D-5L HR-QOL: 0.839, EQ-VAS: 70, and SF-12 MCS 46.7, RCS 41.8). This case suggests that an integrative approach simultaneously targeting neuroinflammation and neurogenesis offers a promising therapeutic option for Long COVID brain fog.},
}
@article {pmid41784006,
year = {2026},
author = {Chiminazzo, LLW and Suffredini, IB and Kirsten, TB},
title = {Psychomotor and neurofunctional sequelae after COVID-19.},
journal = {Acta neuropsychiatrica},
volume = {},
number = {},
pages = {1-32},
doi = {10.1017/neu.2026.10067},
pmid = {41784006},
issn = {1601-5215},
abstract = {OBJECTIVE: A previous study by our research group identified psychomotor and neurofunctional impairments following SARS-CoV-2 infection. This study continues that investigation, aiming to evaluate whether these impairments persisted over time, as part of the broader characterization of long COVID. Moreover, it was explored potential correlations with variables such as age, blood type, symptoms, and medical care.<br><br>METHODS: From an initial pool of 214 subjects, 30 post-COVID-19 participants and 30 healthy controls were selected after strict exclusion criteria. The assessments protocol included eight psychomotor tests-Fine Motor Development (Diadochokinesia, Puppets, Fan, and Paper) and Balance (Immobility, Static Balance on One Foot, Feet in Line, and Persistence)-as well as three cognitive screening tasks from the Mini-Mental State Examination: Episodic Memory After Distracters, Verbal Fluency, and Clock tests. Evaluations were performed at three time points: baseline (post-COVID-19), 12 weeks, and 24 weeks. Participants were stratified by age (18-30, 31-45, and 46-64 years), symptoms profile, medical care, and blood type.<br><br>RESULTS: COVID-19 induced psychomotor and neurofunctional sequelae lasting at least 24 weeks post-infection. These impairments were more pronounced and persistent in the 31-45-years age group, while memory-related impairments were more evident in the 18-30 age group. Body pain, coryza, and sore throat were key symptoms linked to long-term sequelae. Rh-negative blood type was suggested as a potential risk factor.<br><br>CONCLUSION: The findings support that long COVID included sustained psychomotor and neurofunctional sequelae, premature senescence, and associations with specific clinical and biological variables.},
}
@article {pmid41782616,
year = {2026},
author = {Umasugi, MT and Fitriasari, E},
title = {Definition, Symptoms, Risk Factors, Epidemiology, and Autoimmunity of Long COVID.},
journal = {American journal of medicine open},
volume = {15},
number = {},
pages = {100124},
pmid = {41782616},
issn = {2667-0364},
}
@article {pmid41782085,
year = {2026},
author = {Heugno, VJN and Kamdem, OL and Same, EGE and Lele, ECB and Biloa, YM and Ayina, CA and Guyot, J and Bongue, B and Mandengue, SH and Moukoko, CEE},
title = {Factors associated with long COVID in sub-Saharan Africa: a scoping review.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-12942-2},
pmid = {41782085},
issn = {1471-2334},
support = {ANRS283//ANRS - Agence Nationale de la Recherche / Emerging Infectious Diseases/ ; },
abstract = {BACKGROUND: Long COVID is a condition characterized by persistent symptoms of COVID-19 that continue to occur in patients after apparent recovery. Given that, these symptoms may vary from person to person due to clinical, demographic, and genetic factors as well as comorbidities, our review aims to identify and analyze risk factors associated with persistent symptoms of COVID-19 (long COVID) in the specific context of sub-Saharan Africa.<br><br>METHODS: Article searches were conducted in the PubMed, Scopus, African Journals Online (AJOL), Science Direct and Google Scholar databases using the keywords "long COVID" or "long-term COVID-19" or "post-COVID condition" or "post-acute sequelae of COVID-19" and "sub-Saharan Africa" or "sub-Saharan Africans". The obtained data were entered into software for duplication checking. Two reviewers selected and extracted the data. Due to substantial heterogeneity in definitions and study designs, a narrative synthesis approach was adopted. Fifteen studies were included in this review, totaling 8,233 participants previously infected with SARS-CoV-2, with approximately 2,011 patients with long COVID from six countries. Six studies were cross-sectional, three were retrospective, three were cohort studies, two were case-control, and one was a case report.<br><br>RESULTS: The review found that the prevalence of long COVID in sub-Saharan Africa ranged from 2% in Ghana to 66.7% in South Africa. The persistent COVID-19 symptoms most commonly experienced by people living in sub-Saharan Africa were fatigue (reported in 12 studies, 25-66% of patients), cough (7 studies, 9-86%), chest pain (9 studies, 9%-29%), dyspnea (10 studies, 15-45%), palpitations (4 studies, 10-30%), headache (9 studies, 12-38%), and cognitive impairment (6 studies, 8-20%). The main risk factors for the occurrence of persistent COVID-19 symptoms were older age (&#x2c3; 60 years), female sex, low education level, hypertension, type 2 diabetes, cardiovascular disease, length of hospitalization during the acute episode, number of initial COVID-19 symptoms, and initial disease severity.<br><br>CONCLUSION: Long COVID is a reality in sub-Saharan Africa. Fatigue and hypertension have proven to be the most common symptom and risk factor, respectively. The heterogeneity of long COVID definitions across studies limits direct prevalence comparisons. Given the socio-economic challenges, pre-existing comorbidities and differences in health systems in the sub-Saharan region, it is therefore necessary to develop new strategies for care, rehabilitation and treatment (specific to the realities of the sub-Saharan region) targeted at each persistent symptom of COVID-19 in order to resolve this emerging problem and allow patients to have a good quality of life.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid41780984,
year = {2026},
author = {Kudeken, N},
title = {Long COVID and Sex Differences: A Narrative Review.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6969-25},
pmid = {41780984},
issn = {1349-7235},
abstract = {Long COVID (post-COVID-19 condition) is a heterogeneous syndrome of persistent or new symptoms after SARS-CoV-2 infection. While men have higher risks of severe acute COVID-19 and mortality, epidemiological studies consistently show a female predominance in Long COVID, especially among middle-aged women. Interpretation is complicated by variable case definitions (WHO, CDC, NICE) and variant-era differences; however, sex disparities persist across both pre-Omicron and Omicron periods. We review evidence on sex differences in epidemiology, symptom clusters, and longitudinal trajectories, incorporating recent RECOVER findings and emerging data from Japanese cohorts. Potential mechanisms include sexually dimorphic antiviral immunity, hormonal and X-chromosome-linked immunoregulation, autoimmunity, autonomic dysfunction, and gender-related social exposures and health-care access. Recognizing sex- and gender-related determinants can improve differential diagnosis, risk stratification, and individualized management, and should be embedded as core variables in future mechanistic studies and clinical trials.},
}
@article {pmid41779029,
year = {2026},
author = {Dunde, A and Maniyar, P and Vora, N and Khan, AA and Rajput, J and Jain, J and Agrawal, SP and Maheta, D and Frishman, WH and Aronow, WS},
title = {Long COVID Myocarditis: Incidence, Mechanisms, Clinical Implications, and Management.},
journal = {Cardiology in review},
volume = {},
number = {},
pages = {},
doi = {10.1097/CRD.0000000000001229},
pmid = {41779029},
issn = {1538-4683},
abstract = {Long coronavirus disease (COVID) (post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection) is characterized by persistent or new health issues weeks or months after acute COVID-19. Cardiac involvement, including myocarditis, is a notable complication that can occur even after an initially mild infection. To review current literature (2022-2025) on myocarditis in Long COVID, focusing on incidence, pathophysiological mechanisms, clinical presentation, diagnosis, management, prognosis, and future directions. Post-COVID myocarditis remains relatively uncommon but is significantly more frequent than pre-pandemic rates. Myocardial injury in Long COVID is hypothesized to result from multiple mechanisms: persistent viral antigen or RNA in cardiac tissue causing chronic immune activation, immune-mediated damage (including autoimmunity such as anti-heart antibodies), microvascular endothelial dysfunction with impaired perfusion, and maladaptive inflammatory responses. Patients may present with typical myocarditis symptoms (exertional chest pain, dyspnea, palpitations) or atypical features like exercise intolerance, orthostatic tachycardia, or unexplained fatigue. Management is supportive and guided by myocarditis severity: exercise restriction for 3-6 months in confirmed cases, guideline-directed heart failure therapy if ventricular dysfunction is present, anti-inflammatory or immunosuppressive therapy in specific scenarios (eg, corticosteroids in fulminant cases or overlapping multisystem inflammatory syndrome), and therapies targeting pericardial involvement (nonsteroidal anti-inflammatory drugs, colchicine) if present.},
}
@article {pmid41778966,
year = {2026},
author = {da Silva, MD and Speidel, R and Seth, A and Carvalho, HJC and Miglino, MA and Badu-Tawiah, AK},
title = {A paper-based immunoassay with signal amplification for the sensitive detection of nucleocapsid protein toward the diagnosis of long COVID.},
journal = {The Analyst},
volume = {},
number = {},
pages = {},
pmid = {41778966},
issn = {1364-5528},
abstract = {Long COVID is characterized by persistent symptoms, including fatigue, cognitive impairment, and respiratory issues, affecting a considerable number of individuals post-infection. The underlying mechanism is not fully understood, but it has been proposed to involve the reactivation of virus, which subsequently induces immune dysregulation. In this proof-of-concept study, we developed a paper-based immunoassay for the detection of nucleocapsid (N) protein, which, due to its stability and low mutation rate, is a valuable biomarker for detecting the presence of residual virus. By utilizing reporter antibodies conjugated to cleavable ionic probes through dendrimer chemistry, we were able to analyze the immunoassay results with ambient mass spectrometry using on-chip paper spray ionization. The used dendrimer enhanced mass spectrometry sensitivity by enabling the attachment of multiple ionic probes to a single reporter antibody. The method presented here achieved a limit of detection of 2.4 pM for N protein detection from paper. Unlike traditional sensitive COVID tests that are only accessible to hospitalized individuals, our paper-based assay has potential to enable long COVID to be detected under resource-limited settings. Our method was applied to analyze 20 human plasma samples, including 10 from individuals with long COVID and 10 from healthy controls with no history of SARS-CoV-2 infection. We observed a significantly higher MS signal-by up to two orders of magnitude-for samples collected from long COVID patients compared to controls. The ability to use the paper device in remote locations was tested by evaluating the stability of the assay, which showed that after 30 days of storage at room temperature, the device retained sufficient analytical performance. Given its robustness, we believe that our platform will be suitable for direct-to-consumer testing, enabling individuals with low viral loads to be screened in a timely fashion.},
}
@article {pmid41778126,
year = {2026},
author = {Meier-Maiwald, M and Riester, T and Stölting, A and Klawonn, F and Thölking, T and Beinhauer, K and Lampe, V and Theil, LM and Schröder, D and Behrens, GM and Von Wasielewski, I and Müller, F and Steffens, S and Dopfer-Jablonka, A and Happle, C and Mikuteit, M},
title = {Post-COVID fatigue disproportionately affects women: evidence from the DEFEAT Corona cohort.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1755106},
pmid = {41778126},
issn = {2296-2565},
abstract = {BACKGROUND: Post COVID syndrome (PCS) affects approximately 6-10% of COVID-19 survivors, with fatigue being one of the most prevalent and debilitating symptoms. While emerging evidence suggests sex and gender-based differences in PCS manifestation, the specific impact on fatigue-related symptoms remains poorly understood, particularly regarding women's experiences.<br><br>METHODS: We analyzed data from 2,549 participants with PCS (80.6% female, 19.2% male, 0.2% non-binary) from DEFEAT, an online platform surveying people with and without PCS. Participants with confirmed SARS-CoV-2 infection were included if they reported symptoms typical for PCS persisting >4&#x202f;weeks post-infection. Fatigue-related symptoms including fatigue, brain fog, sleep disturbances, and associated quality of life measures were assessed using validated instruments.<br><br>RESULTS: Female participants reported significantly higher rates of fatigue-related symptoms compared to males: fatigue was more prevalent in females (53.5% vs. 46.3%, p&#x202f;<&#x202f;0.001), as were brain fog (54.9% vs. 44.7%, p&#x202f;<&#x202f;0.001), and sleep disturbances (54.8% vs. 45.3%, p&#x202f;<&#x202f;0.001). Female participants also reported significantly higher fatigue severity scores and poorer health-related quality of life (mean EQ-5D score 0.66 (SD 0.23) vs. 0.71 (SD 0.23) in males, p&#x202f;<&#x202f;0.001). Around two thirds of menstruating PCS patients reported menstrual cycle associated worsening of fatigue symptoms.<br><br>CONCLUSION: Our findings demonstrate significant gender-based differences in fatigue-related symptoms in PCS, with women experiencing both higher prevalence and severity, and menstrual cycle associated symptom worsening. These results highlight the importance of sex and gender-specific approaches to understanding and managing PCS-related fatigue, with implications for clinical care and future research directions.},
}
@article {pmid41776429,
year = {2026},
author = {Lindberg, P and Lindblom, S and Ljunggren, G and Lee, S and Kolosenko, I and Runold, M and Fedorowski, A and Wachtler, C and Piontkovskaya, K and Wheelock, &#xc5;M and Carlsson, AC},
title = {Association of pre-pandemic respiratory system diseases with long COVID: a population-based case-control study.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-12977-5},
pmid = {41776429},
issn = {1471-2334},
}
@article {pmid41775811,
year = {2026},
author = {Omdal, R and Lenning, OB and Jonsson, G and Kvaløy, JT and Di Molfetta, G and Tan, K and Benedet, AL and Ashton, NJ and Braut, GS and Zetterberg, H and Grimstad, T},
title = {Long-COVID: assessment of circulating markers suggests no cerebral neuronal damage, neuroinflammation or systemic inflammation-a controlled study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-40142-0},
pmid = {41775811},
issn = {2045-2322},
abstract = {Long-COVID remains incompletely understood, particularly regarding the roles of peripheral systemic inflammation and neuroinflammation. The persistence and extent of these processes remain debated. We conducted a single-center, age- and sex-matched case-control study at Stavanger University Hospital, Norway, recruiting participants from the general population. Forty-eight long-COVID patients and 48 recovered controls were included at a median of 69 weeks post-SARS-CoV-2 infection. Exclusion criteria included autoimmune or chronic inflammatory diseases, cancer, and other conditions affecting fatigue. Plasma levels of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using ultrasensitive NULISA™ technology. CRP, TNF-α, and IL-6 were additionally assessed by a standard hospital laboratory method (CRP) and MSD S-Plex chemiluminescence immunoassay (TNF-α and IL-6 MSD). No significant differences in NfL or GFAP were observed between groups, suggesting no ongoing neuronal injury or neuroinflammation. Routine immunoassays showed no differences for inflammatory markers. In unadjusted analyses using ultrasensitive assays, long-COVID patients showed nominally elevated levels of CRP (p = 0.04), TNF-α (p = 0.01), IL-6 (p = 0.02), and TREM2 (p = 0.02). However, these differences did not survive correction for multiple comparisons (all false discovery rate-adjusted p > 0.05). The absence of neuroinflammation markers is consistent with the hypothesis that persistent long-COVID symptoms are unlikely due to ongoing neuronal injury or central nervous system inflammation. Alternatively, persisting long-COVID symptoms may reflect a chronic, extremely low-level immune activation, that contributes to fatigue, pain, and other sickness phenomena through mechanisms such as pro-inflammatory signaling in the brain, or epigenetic mechanisms underlying the sickness behavior response. These findings should be considered preliminary and warrant validation in larger, longitudinal cohorts.},
}
@article {pmid41774869,
year = {2026},
author = {Kumar, A and Tang, E and Xu, X and Vo, A and Arnold, BF and Acharya, NR},
title = {Risk Factors for Long COVID Among Individuals with Noninfectious Uveitis in a Large United States Claims Database.},
journal = {Ocular immunology and inflammation},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/09273948.2026.2626820},
pmid = {41774869},
issn = {1744-5078},
abstract = {PURPOSE: Patients with noninfectious uveitis (NIU) may be more susceptible to complications of COVID-19, including long COVID, yet limited research has evaluated this outcome in NIU populations. This study aimed to assess the prevalence and risk factors of long COVID among individuals with NIU in the United States.<br><br>METHODS: A retrospective cohort analysis was conducted using de-identified data from a large healthcare claims database. A time-varying Cox proportional hazard regression analysis was performed to estimate the effects of various risk factors on the development of long COVID. Models were adjusted for use of systemic corticosteroids and other immunosuppressive medications, comorbidities, COVID-19 vaccination status, and demographic variables.<br><br>RESULTS: The study population consisted of 63&#x2009;220 individuals with NIU (mean age (SD)&#x2009;=&#x2009;62.9 (17.4) years, 60.7% female). There were 621 (0.096%) documented cases of long COVID across 100&#x2009;105.6 person-years, representing an incidence rate of 6.2 cases of long COVID per 1000 person-years. Exposure to systemic corticosteroids was associated with an average increased risk of long COVID (hazard ratio (HR)&#x2009;=&#x2009;3.45, 95% CI: 2.68-4.46, p&#x2009;<&#x2009;0.001). Additionally, COVID-19-related hospitalizations, increased healthcare utilization, and having baseline asthma and mental health disorders were also associated with an average increased risk of long COVID (all p&#x2009;<&#x2009;0.003). Male sex, topical or local corticosteroid exposure, and COVID-19 vaccination were associated with an average decreased risk of long COVID (all p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: This large population-based study identified key risk and protective factors for long COVID among patients with NIU. Findings suggest that systemic corticosteroid-induced immune dysregulation may increase vulnerability to long COVID in individuals with severe uveitis.},
}
@article {pmid41774679,
year = {2026},
author = {Pavón, R and Parra, S and Rubio, FJ and Feliu, M and Ríos, M and Iftimie, S and Rovira, C and Amigó, N and Cabau, L and Martínez-Micaelo, N and Castro, A},
title = {Assessment of physical status and analysis of lipidomic and metabolomic alterations in patients with Post-COVID-19 condition.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0341192},
pmid = {41774679},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/metabolism/complications/physiopathology ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; *Lipidomics ; Prospective Studies ; *Metabolome ; Metabolomics ; Hand Strength/physiology ; Adult ; Aged ; SARS-CoV-2 ; },
abstract = {The development and persistence of symptoms following SARS-CoV-2 infection, known as Post-COVID-19 Condition (PCC) or "long COVID," represents a global health challenge. In this prospective cross-sectional study, we conducted a detailed assessment of the physical condition of 46 patients using handgrip dynamometry, ergoespirometry, and the 6-minute walk test (6MWT). The results revealed a loss of muscle strength and poor exercise tolerance primarily due to peripheral muscle involvement. To complement and better understand these findings, we compared the blood metabolome and lipidome of 13 patients with PCC, 13 patients with acute COVID-19 infection, and 13 healthy controls using magnetic resonance spectroscopy (1H-NMR). PCC patients showed lower levels of HDL-cholesterol, as well as medium and dense HDL particles, which could contribute to a pro-atherogenic and pro-inflammatory state. Although no significant differences were observed in glycoproteins, we found decreased glucose and increased lactate levels, supporting the hypothesis of mitochondrial dysfunction in PCC patients. Additionally, elevated glycine and reduced glutamate levels may be related to the neurological symptoms associated with the condition. We also observed increased levels of glutamine, leucine, and isoleucine, indicating protein hypercatabolism and metabolic stress. These findings suggest that alterations in the metabolome and lipidome of PCC patients may be contributing to the persistence of their symptoms.},
}
@article {pmid41772376,
year = {2026},
author = {Frontera, JA and Masurkar, AV and Betensky, RA and Alvarez, Z and Boutajangout, A and Chodosh, J and Hammam, S and Hunter, J and Jiang, L and Li, M and Links, J and Marsh, K and Pang, H and Silva, F and Thawani, S and Vasilchenko, D and Vedvyas, A and Yakubov, A and Ge, Y and Wisniewski, T},
title = {Increased incidence of mild cognitive impairment in long COVID patients.},
journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71237},
pmid = {41772376},
issn = {1552-5279},
support = {R01AG077422//NIH/NIA/ ; R01AG092774//NIH/NIA/ ; P30AG066512//NIH/NIA/ ; },
abstract = {INTRODUCTION: Though brain fog is common in Long-coronavirus disease 2019 (Long-COVID), the incidence of mild cognitive impairment (MCI) is unknown.<br><br>METHODS: In an observational cohort study, recovered COVID-positive, Long-COVID, and COVID-negative subjects underwent blinded evaluation using National Alzheimer's Coordinating Center (NACC) and National Institute on Aging (NIA) -Alzheimer's Association diagnostic criteria for dementia and MCI. The cumulative incidence of MCI was calculated for each group, and the hazard of MCI was compared between groups.<br><br>RESULTS: Among 260 subjects, the cumulative incidence of MCI over 4.4 years was higher with Long-COVID (27%)&#xa0;versus recovered-COVID (5%) or COVID-negative status (1%). There was a higher hazard of MCI for patients with Long-COVID compared to those without (hazard ratio [HR] 3.93, 95% confidence interval [CI] 1.86-8.31, p&#xa0;<&#xa0;0.001), and specifically for the Alzheimer's disease (AD) -related MCI subtype (HR 3.20, 95% confidence interval [CI] 1.14-9.00, p&#xa0;=&#xa0;0.027).<br><br>DISCUSSION: The cumulative incidence and adjusted hazard of MCI (and specifically AD-related MCI) at 4.4 years was significantly higher among Long-COVID patients compared to recovered-COVID and COVID-negative controls.},
}
@article {pmid41771995,
year = {2026},
author = {Liu, F and Xia, Y and Lee, AC and Chen, Y and Chen, Z and He, Y and Chan, CH and Cai, J and Yuen, TT and Ye, ZW and Zhang, J and Qian, Z and Yuen, KY and Chan, JF and Chu, H},
title = {Prolonged dysregulation and pathological changes in the upper respiratory tract of SARS-CoV-2 infected hamsters.},
journal = {Npj viruses},
volume = {4},
number = {1},
pages = {},
pmid = {41771995},
issn = {2948-1767},
support = {17118621, 17119122//General Research Fund/ ; C7103-22G//Collaborative Research Fund/ ; T11-709/21-N//Theme-Based Research Scheme/ ; HKU RFS2425-7S06//Research Fellow Scheme/ ; COVID1903010-14, 23220522, CID-HKU1-5//the Health and Medical Research Fund/ ; projects 2021YFC0866100 and 2023YFC3041600//National Key Research and Development Program of China/ ; 2023A1515012325, 2023A1515011891, 2024A1515010848, 2023A1515011910//General Programme, Guangdong Provincial National Science Foundation, China/ ; },
abstract = {Respiratory long COVID symptoms, including dyspnea and breathing pattern disorders, are frequently reported in convalescent COVID-19 patients. Yet the mechanisms driving these persistent respiratory manifestations remain poorly elucidated. In this study, we characterized persistent upper respiratory tract pathology in SARS-CoV-2-infected hamsters. Strikingly, we observed persistent expression of SARS-CoV-2 nucleocapsid (N) protein and subgenomic RNA (sgRNA) gene, which resulted in sustained tissue pathologies, dysregulation of pro-inflammatory markers, pro-apoptotic genes, as well as the altered expression of viral entry receptors, in the nasal turbinate of infected hamsters up to 120 days post-infection. These findings indicate that residual viral components may contribute to dysregulation of tissue repair and remodeling, chronic tissue pathology, and potentially enhanced susceptibility to secondary respiratory infections upon SARS-CoV-2 infection even upon recovery of acute infection. Collectively, our study provides insights into potential drivers of post-acute COVID-19 sequelae in the upper respiratory tract.},
}
@article {pmid41771135,
year = {2026},
author = {Lim, SY and Lee, J and Chang, E and Kwon, JS and Jang, CY and Seo, Y and Park, JJ and Na, SH and Park, H and Jang, HM and Yun, SC and Kim, SH},
title = {Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19 : A Randomized Clinical Trial.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-04883},
pmid = {41771135},
issn = {1539-3704},
abstract = {BACKGROUND: There is no proven treatment to alleviate symptoms of postacute sequelae of SARS-CoV-2 infection (PASC), despite its substantial public health burden.<br><br>OBJECTIVE: To evaluate the efficacy of metformin and ursodeoxycholic acid (UDCA) in improving PASC symptoms in adults.<br><br>DESIGN: Double-blind, placebo-controlled, randomized clinical trial. (Clinical Research Information Service: KCT0009342).<br><br>SETTING: Two tertiary hospitals in South Korea, July 2024 to April 2025.<br><br>PARTICIPANTS: Of 666 adults screened, 396 with a PASC index score of 12 or greater were randomly assigned.<br><br>INTERVENTION: Oral metformin (uptitrated to 1500 mg/d), UDCA (900 mg once daily), or double placebo for 14 days (1:1:1).<br><br>MEASUREMENTS: Proportion of participants achieving PASC recovery (index score <12) at 8 weeks.<br><br>RESULTS: Among 396 randomized participants (median age, 36 years [IQR, 28 to 49 years]; 72% women), 132 received metformin, 132 received UDCA, and 132 received placebo. The mean interval from SARS-CoV-2 infection was 9.8 months (SD, 7.5). The mean baseline PASC score was 19.3 (SD, 5.7). Recovery occurred in 63.6% (84 of 132) with metformin, 68.2% (90 of 132) with UDCA, and 68.2% (90 of 132) with placebo. Mean changes in PASC scores from baseline to week 8 were -10.05 (95% CI, -11.35 to -8.76) with metformin and -10.62 (CI, -11.79 to -9.45) with UDCA, compared with -10.43 (CI, -11.69 to -9.18) with placebo.<br><br>LIMITATION: Findings may not be generalizable to patients with more severe or persistent long COVID.<br><br>CONCLUSION: A 2-week course of metformin or UDCA did not significantly improve recovery from PASC.<br><br>PRIMARY FUNDING SOURCE: National Institute of Infectious Diseases, National Institute of Health, South Korea.},
}
@article {pmid41770566,
year = {2026},
author = {Shah, RM and Shah, KM and Chen, J and Sawano, M and Bhattacharjee, B and Krumholz, HM},
title = {Long COVID and Recovery Among US Adults.},
journal = {JAMA network open},
volume = {9},
number = {3},
pages = {e260374},
pmid = {41770566},
issn = {2574-3805},
}
@article {pmid41768981,
year = {2026},
author = {Lim, L and Hosseinkhah, N and Van Buskirk, M and Oei, K and Berk, A and Pushparaj, A and Liburd, J and Abbaspour, Z and Rubine, J and Jackson, D and Zomorrodi, R},
title = {Photobiomodulation for cognitive dysfunction (Brain Fog) in post-COVID-19 condition: a randomized double-blind sham-controlled pilot trial.},
journal = {EClinicalMedicine},
volume = {92},
number = {},
pages = {103730},
pmid = {41768981},
issn = {2589-5370},
abstract = {BACKGROUND: Post-COVID-19 condition (PCC) affects millions globally, with cognitive dysfunction ("brain fog") impairing daily functioning in up to 88% of patients. No effective treatments exist for PCC-related cognitive impairment. Photobiomodulation (PBM), a non-invasive therapy delivering near-infrared light, enhances mitochondrial function and reduces neuroinflammation, showing promise in neurological disorders. This study aimed to evaluate the efficacy and safety of home-based intranasal and transcranial PBM (itPBM) for PCC cognitive dysfunction.<br><br>METHODS: This randomized, double-blind, sham-controlled pilot trial in the USA (ClinicalTrials.govNCT05857124) enrolled 43 adults (18-65 years) with PCC cognitive symptoms &#x2265;12 weeks post-infection. Participants were randomized 1:1, stratified by age (<45 vs &#x2265; 45 years), using computer-generated assignment to 8 weeks of daily 20-min itPBM, 6 days per week, with the Vielight Neuro RX Gamma device or sham, targeting the brain's default mode network, followed by 4 weeks of observation. Participants, investigators, and assessors were masked to group assignment. The primary outcome was mean change in Creyos cognitive battery composite score at Day 56. Secondary outcomes included fatigue, quality of life, and safety. Analyses used mixed-model repeated measures in the per-protocol population.<br><br>FINDINGS: The trial was completed, with 43 participants randomized (23 active, 20 sham) and 41 analyzed (21 active, 20 sham). They were recruited between July 5, 2023, and September 1, 2024. Active itPBM improved composite cognitive scores more than sham (mean difference 0.043, 95% CI -0.007 to 0.092, p = 0.088), with significant gains in participants <45 years (prespecified but exploratory, p = 0.028). Attention tasks improved consistently (p < 0.050 at multiple timepoints). Secondary outcomes mobility favored sham (p = 0.007), and fatigue also favored sham. No serious adverse events occurred; compliance was high (median 55 days, interquartile range 2 days).<br><br>INTERPRETATION: Home-based itPBM is safe and feasible, showing potential cognitive benefits for PCC brain fog, particularly in younger adults. Larger trials are needed to confirm efficacy and optimize parameters.<br><br>FUNDING: Vielight Inc.},
}
@article {pmid41768410,
year = {2026},
author = {Hung, TS},
title = {Rehabilitation strategies for long COVID: integrating human factors engineering.},
journal = {Frontiers in rehabilitation sciences},
volume = {7},
number = {},
pages = {1708460},
pmid = {41768410},
issn = {2673-6861},
abstract = {Long COVID presents unique challenges that extend beyond conventional biomedical rehabilitation, necessitating strategies that are adaptive, multidisciplinary, and patient-centered. This mini-review synthesizes current evidence on physical, cognitive, and occupational rehabilitation, and introduces human factors engineering as a framework to optimize the design, delivery, and usability of interventions. Emerging approaches such as telerehabilitation, cognitive ergonomics, and structured return-to-work programs illustrate the value of integrating clinical rehabilitation with user-centered design. Yet critical gaps remain, including the limited number of randomized controlled trials, the heterogeneity of outcome measures, and the lack of systematic integration between rehabilitation and human factors research. Addressing these challenges will be essential to develop effective, scalable, and sustainable interventions. By aligning rehabilitation protocols with the principles of human factors engineering, future practice can better enhance efficacy, promote sustained patient engagement, and ultimately improve the quality of life for individuals living with long COVID.},
}
@article {pmid41767632,
year = {2026},
author = {Ziauddeen, N and Pantelic, M and O'Hara, ME and Hastie, C and Alwan, NA},
title = {Symptom Patterns, Recovery, and Impact of Long COVID: Findings From a Longitudinal Survey.},
journal = {Open forum infectious diseases},
volume = {13},
number = {2},
pages = {ofag040},
pmid = {41767632},
issn = {2328-8957},
abstract = {BACKGROUND: Long COVID is a predominantly multisystem, often disabling, condition that develops following SARS-CoV-2 infection. We aimed to characterize the pattern, triggers, and impact of Long COVID symptoms.<br><br>METHODS: Data from a 1-year follow-up of an online survey originally conducted in November 2020 were used. Surveys were coproduced with people living with Long COVID. Participants were adults with Long COVID following confirmed or probable SARS-CoV-2 infection who were not hospitalized in the first 2 weeks of illness. The baseline survey recruited from social media and online support groups using convenience nonprobability sampling.<br><br>RESULTS: Of the 2210 first survey participants invited, 1153 (52%) responded to the follow-up survey. The mean age was 47.7 years (standard deviation 10.6) with 84% females, 83% UK-based, 78% university-qualified, and 90% reporting good to excellent health before SARS-CoV-2 infection. Median duration of illness was 19.8 months (interquartile range, 19.3-20.1) at follow-up. Only 5% of participants reported full recovery, and 45% reported a constant pattern of illness (as opposed to fluctuating or relapsing) compared to 17% at baseline. An equal proportion reported being unable to work at baseline (20.4%) and follow-up (20.6%). However, a higher proportion reported being made redundant or taking early retirement at follow-up (8.9%) than at baseline (2.2%).<br><br>CONCLUSIONS: This study highlights the prolonged nature of Long COVID as well as the impact on work. This has the potential to widen health inequalities and increase hardship in individuals whose life circumstances and job types may not allow them to make necessary adaptations.},
}
@article {pmid41766190,
year = {2026},
author = {Smyth, N and Ahmad, A and Begum, S and Chaudhry, A and Clark, S and Wright, A and Gimblett, K and Ridge, D and Chew-Graham, CA and Gopal, D and Alwan, NA and Kingstone, T},
title = {Co-Creating Publicly Available Resources to Increase Awareness of and Support for Long Covid Among Ethnic Minority Communities.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70596},
pmid = {41766190},
issn = {1369-7625},
support = {NIHR203106//National Institute for Health Research/ ; },
mesh = {Humans ; *COVID-19/ethnology/psychology ; *Minority Groups/psychology ; *Ethnicity/psychology ; Female ; United Kingdom ; Male ; Social Stigma ; SARS-CoV-2 ; Middle Aged ; Adult ; Interviews as Topic ; },
abstract = {INTRODUCTION: Stigma and discrimination make healthcare challenging for people living with Long Covid, especially those from ethnic minority groups. Since their experiences are under-researched and may differ from other groups, it is crucial that healthcare guidance is informed by the lived experiences of diverse groups.<br><br>METHODS: Findings from underpinning research (hearing from the unheard: Impact of Long Covid in Black and minority ethnic groups in the UK: HI-COVE - 31 interviews with ethnic minority individuals living with Long Covid) informed the development of two resources aimed at raising awareness of the challenges faced by ethnic minority groups and offer ways to best support these groups. People living with Long Covid (N&#x2009;=&#x2009;4) provided feedback on the two resources. Feedback was guided by a topic guide. Minimal changes were made following feedback.<br><br>RESULTS: Resource 1: Four participants who took part in the underpinning research, worked with an Artist (AW) to curate artwork. The artwork created was a video called 'Still Looking for Answers' https://www.youtube.com/watch?v=GDt-Ro1Cql8&amp;t=1s. It comprises anonymised patient narratives and imagery (performed by actors) and a soundscape to convey ethnic minority lived experiences of Long Covid. Resource 2: an online learning tool called 'Health and Social Care PROfessional-Long Covid': H-Pro-LC tool: https://clineduniverse.org/hicove/story_html5.html shares challenges people from ethnic minority groups face when accessing healthcare for Long Covid. The resource includes guidance on supporting people, particularly people from ethnic minority backgrounds, presenting to primary care with (probable) symptoms of Long Covid.<br><br>CONCLUSIONS: These publicly available resources aim to raise awareness of Long Covid: they encourage viewers to emotionally connect with experiences of Long Covid as well as offer ways to support people living with the condition, particularly among people from ethnic minority groups.<br><br>The underpinning research of these resources were extensively informed by both patient (N&#x2009;=&#x2009;7) and expert advisory groups (N&#x2009;=&#x2009;6). Co-creation approaches (through workshops, meetings and written feedback) from people living with Long Covid, carers, stakeholders and members of the public informed the design, development, innovation and impact of resources developed. People with lived experience of Long Covid provided feedback on the resources developed in this study.},
}
@article {pmid41766005,
year = {2026},
author = {Zawadzki, J and Kania, J and Murkos, M and Zgoła, D and Noga, A and Nowak, P and Kulińska, W and Pawlik, P and Kudliński, B},
title = {Four year mortality and quality of life after ICU treatment for COVID 19 related acute respiratory distress syndrome.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42341-1},
pmid = {41766005},
issn = {2045-2322},
abstract = {Severe COVID-19 leading to ARDS and ICU admission is associated with high early mortality, yet data on long-term outcomes and societal burden remain limited, particularly in Central and Eastern Europe. To describe 4-year mortality, patient-reported functional status and health-related quality of life (HRQoL) among ICU-treated COVID-19 ARDS patients, and to explore early factors associated with short- and long-term mortality as well as long-term recovery. Single-center retrospective-prospective cohort study with structured 4-year telephone follow-up. 283 adults treated in the Temporary ICU Hospital in Zielona Góra, Poland (December 2020-July 2021). Follow-up interviews were completed in 81 of 157 confirmed 4-year survivors. Associations with 30-day mortality and late mortality (among 30-day survivors) were explored using multivariable logistic regression. Survivors completed a structured interview assessing HRQoL (EQ-5D-5 L/EQ-VAS), dyspnoea severity assessed with the mMRC scale, functional status assessed with PCFS, fatigue, brief cognitive screening items, return to work, rehabilitation use, and financial burden. A cumulative post-ICU impairment score (0-6 domains) was constructed. Cost estimates were exploratory and based on public ICU reimbursement rates and patient-reported rehabilitation burden. Thirty-day mortality was 29.0%, and cumulative 4-year mortality was 45%. In adjusted analyses, older age and higher white blood cell count at ICU admission were associated with mortality endpoints (model discrimination up to AUC 0.86, depending on endpoint). Among 4-year survivors, 27.5% reported clinically relevant fatigue, 46.8% insomnia, and a substantial proportion reported persistent limitations across functional and EQ-5D domains. Rehabilitation was reported by 39% and was associated with lower QALY, likely reflecting greater baseline impairment. Median 4-year QALY was 3.7, varying significantly by fatigue, dyspnoea, return-to-work status, and subjective cognitive complaints. Among ICU-treated COVID-19 ARDS patients, long-term mortality remained high and many survivors reported persistent multidomain impairment years after discharge. These findings support structured post-ICU follow-up pathways and targeted rehabilitation and occupational support for long-COVID survivors.},
}
@article {pmid41764705,
year = {2026},
author = {Kirwin, E and Adibnia, E and Wiggins, M and Sander, B and Xie, F and Ohinmaa, A and Johnson, JA and Norris, C and Rafferty, E and MacDonald, SE and Round, J and , },
title = {The impact of testing positive versus negative for COVID-19 on health-related quality of life: cross-sectional evidence from the Alberta post-COVID-19 follow-up survey.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {4},
pages = {},
pmid = {41764705},
issn = {1573-2649},
support = {FRN#173622//Canadian Immunization Research Network/ ; FRN#173622//Canadian Immunization Research Network/ ; },
}
@article {pmid41761660,
year = {2026},
author = {Geng, S and Li, L},
title = {Immune exhaustion, the culprit for long COVID and chronic complications.},
journal = {Journal of leukocyte biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jleuko/qiag029},
pmid = {41761660},
issn = {1938-3673},
}
@article {pmid41758880,
year = {2026},
author = {Meyer, F and Traidl, S and Ameri, M and Dreher, A and Abu-Rashed-Kufs, N and Vontobel, J and Möhrenschlager, M and Duchna, HW and Sandberg, F and Brüggen, MC},
title = {Distinguishing post-COVID from long-COVID in adults: Development and validation of a biomarker signature using targeted proteomics and machine learning in a cross-sectional observational study.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0338451},
pmid = {41758880},
issn = {1932-6203},
mesh = {Humans ; Female ; *COVID-19/diagnosis/blood/metabolism ; Male ; *Machine Learning ; Middle Aged ; *Biomarkers/blood ; Cross-Sectional Studies ; *Proteomics/methods ; Adult ; Prospective Studies ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: COVID-19 can have diverse clinical manifestations, ranging from asymptomatic infection to critical illness with multiorgan involvement. While many patients recover fully, others develop long-COVID, a heterogeneous condition marked by persistent symptoms beyond the acute phase. The immunological pathomechanisms between long-COVID and other post-acute recovery states remain unclear.<br><br>OBJECTIVE: To characterize and compare clinical, pulmonary, and proteomic profiles of patients with long-COVID (LC) and those recovering from severe COVID-19 without long-COVID (post-severe-COVID, PC), and to evaluate the predictive potential of machine learning-based biomarker analysis.<br><br>METHODS: In this monocentric, prospective observational study with a cross-sectional design, patients undergoing rehabilitation were included at admission. Clinical data, detailed symptom profiles, and lung function testing, including diffusing capacity of the lungs, were collected. Serum proteomics covering immune response and inflammation panels was performed, and a Random Forest classifier was applied to identify biomarkers differentiating LC and PC.<br><br>RESULTS: LC (n&#x2009;=&#x2009;24) patients were younger (52 years vs. 58 years in PC), predominantly female (66.7% vs. 30.0% in PC), and reported fatigue, neurocognitive symptoms, and exercise intolerance, whereas PC (n&#x2009;=&#x2009;40) patients showed greater pulmonary impairment, as shown by reduced diffusing capacity (46% vs. 72.5% in LC p<0.001). Proteomic profiling revealed distinct immune and inflammatory signatures between groups. Applying a random forest classification algorithm, we were able to distinguish between the LC and the PC group with a high degree of accuracy of around 89%, using LAMP3 (Lysosome-associated membrane glycoprotein 3), CKAP4 (cytoskeleton associated protein 4) and KRT19 (Keratin 19).<br><br>CONCLUSIONS: This study introduces a novel characterization of patients recovering from severe COVID-19 without long-COVID, enabling clearer differentiation between persistent and recovering trajectories. Combining clinical data, pulmonary function, and proteomic machine learning analysis provides insight into post-acute COVID-19 biology and identifies candidate biomarkers for improved diagnosis.},
}
@article {pmid41757223,
year = {2026},
author = {Agyemang, C and Norredam, M},
title = {Beyond broad categories: understanding ethnic differences in long COVID.},
journal = {The Lancet regional health. Europe},
volume = {63},
number = {},
pages = {101622},
pmid = {41757223},
issn = {2666-7762},
}
@article {pmid41756785,
year = {2026},
author = {Fanelli, M and Petrone, V and Chirico, R and Coppola, L and Sorace, C and Cipriani, C and Longo, G and Girasole, M and Collacchi, F and Radu, CM and Miele, MT and Lucas, A and Teti, E and Malagnino, V and Iannetta, M and Malergue, F and Bernardini, S and Balestrieri, E and Sarmati, L and Grelli, S and Minutolo, A and Matteucci, C},
title = {CD169[+] and HLA-DR[+] extracellular vesicles are highly represented in human plasma and dynamically expressed in SARS-CoV-2 infection and long COVID-associated sequelae.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1686186},
pmid = {41756785},
issn = {2235-2988},
mesh = {Humans ; *Extracellular Vesicles/metabolism/immunology ; *COVID-19/immunology/blood/complications/pathology ; *HLA-DR Antigens/blood ; Male ; Middle Aged ; Female ; SARS-CoV-2 ; *Sialic Acid Binding Ig-like Lectin 1/blood/metabolism ; Monocytes/immunology ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Biomarkers/blood ; },
abstract = {INTRODUCTION: Elevated inflammation and immune dysregulation are the main consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The dysregulated inflammatory state persists after coronavirus disease 2019 (COVID-19), establishing the post-acute sequelae of SARS-CoV-2 infection in individuals with long COVID (LC). The role of CD169[+] monocytes in the early diagnosis of SARS-CoV-2 infection and their association with severe outcomes were demonstrated in COVID-19 patients (COV). We aimed to delineate specific myeloid activation that characterizes the acute and post-acute phases of SARS-CoV-2 infection, evaluating the correlation between cellular and extracellular vesicles (EVs).<br><br>METHODS: Blood samples from COV, LC, and healthy donors (HD) were collected at Tor Vergata University Hospital in Rome. Plasmatic EVs were isolated by differential centrifugation and evaluated by flow cytometry and atomic force microscopy (AFM). Leukocyte subpopulations and different sizes of circulating EVs (100-200, 240-500, >500 nm) were characterized for HLA-DR and CD169 expression in COV, LC, and HD through flow cytometry. Serum inflammatory markers were assessed by the ELLA immunoassay system. The analyzed markers were associated with clinical and biochemical parameters in COV and LC.<br><br>RESULTS: The analysis of HLA-DR[+], CD169[+], and HLA-DR[+]CD169[+] leukocytes confirmed our previous results in which the activated monocytes CD169[+]HLA-DR[+] were found significantly high in COV, persisting in LC, and correlated differently with coagulation markers and inflammatory cytokines. Similar to cellular levels, the percentage and number of HLA-DR[+]CD169[+] EVs were significantly elevated in COV and persisted in LC compared to HD. Different HLA-DR and CD169 expressions were found according to EV size in COV, LC, and HD, and correlations with biochemical parameters and circulating inflammatory markers were found. A positive correlation of HLA-DR and CD169 expression among monocytes and circulating EVs was found, supporting a possible connection between the two compartments and circulating inflammatory mediators. Moreover, the characterization by flow cytometry of EV cell derivation and cytokine cargo revealed EVs as sensitive indicators of both acute and persistent immune perturbations, bridging viral antigen persistence with inflammatory signaling in long COVID.<br><br>CONCLUSION: Myeloid activation markers and inflammatory cytokines are dynamically expressed between blood cells and circulating extracellular vesicles, underlining multilevel cell-to-cell communications, opening new possibilities to monitor COVID-19 and long COVID-associated sequelae.},
}
@article {pmid41756626,
year = {2026},
author = {Pleguezuelos, E and Del Carmen, A and Sánchez-Nuño, S and Serra-Payá, N and Moreno, E and Molina-Raya, L and Jerez-Molina, C and Girabent Farrés, M and Castizo-Olier, J and Biurrun-Garrido, A and Viñals, X and Serra-Prat, M and Garnacho-Castaño, MV},
title = {Extracellular-to-total body water ratio is associated with comorbidity and cardiorespiratory fitness in older adults with post-COVID-19 syndrome.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1715783},
pmid = {41756626},
issn = {2296-861X},
abstract = {BACKGROUND: Post-coronavirus disease 2019 (post-COVID-19) syndrome is associated with persistent impairments in physical fitness and altered body composition, particularly in older adults. The extracellular-to-total body water (ECW/TBW) ratio has been linked to poor outcomes in clinical populations. However, its association with cardiorespiratory fitness (CRF) and muscular fitness (MF) in older adults with post-COVID-19 syndrome remains unclear. This study aimed to examine the associations between ECW/TBW ratio, CRF, MF, and other variables in this population.<br><br>METHODS: A cross-sectional study was conducted in 71 older adults with post-COVID-19 syndrome. Hydration status and body composition were assessed using bioelectrical impedance analysis (BIA). CRF was evaluated by cardiopulmonary exercise testing (CPET; peak oxygen uptake, VO2peak), and MF was assessed using isokinetic and functional performance tests. Associations between ECW/TBW ratio, fitness outcomes, and other variables were analyzed through multi-variate linear regression models adjusted for age and sex. Results: Higher ECW/TBW ratio was significantly associated with lower VO2peak (&#x3b2; = -0.010, p = 0.048) and greater comorbidity burden (&#x3b2; = 0.003, p = 0.002). No significant associations were observed between ECW/TBW ratio and MF variables (p > 0.05).<br><br>CONCLUSIONS: The ECW/TBW ratio is independently associated with comorbidity burden and CRF, but not with MF, in older adults with post-COVID-19 syndrome. The Charlson Comorbidity Index emerged as the strongest determinant of ECW/TBW ratio. These findings highlight the potential relevance of integrating hydration monitoring and CRF assessment into rehabilitation strategies, and support further investigation of their role in the clinical management of older adults with post-COVID-19 syndrome.},
}
@article {pmid41754590,
year = {2026},
author = {De Stefanis, S and Colavita, F and Maggi, F and Antonioli, M},
title = {SARS-CoV-2 Persistence and the Gut Microbiota: New Insights into Long COVID Pathogenesis.},
journal = {Viruses},
volume = {18},
number = {2},
pages = {},
pmid = {41754590},
issn = {1999-4915},
support = {Ricerca Corrente Linea 1 - Progetto 1 to IRCCS INMI L. Spallanzani//Ministero della Salute/ ; Ricerca di Ateneo 2024- Dipartimento di Biologia (AutoCuRC)//University of Rome Tor Vergata/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/complications/microbiology/virology/immunology/pathology ; *SARS-CoV-2/physiology/pathogenicity ; Dysbiosis/microbiology ; Inflammation ; Gastrointestinal Tract/virology/microbiology ; Inflammatory Bowel Diseases/microbiology ; },
abstract = {In December 2019, the world experienced the emergence of a new virus, SARS-CoV-2, which caused the 2020 pandemic. SARS-CoV-2 causes COVID-19, primarily affecting the respiratory system, as well as the gastrointestinal tract. Remarkably, one in eight COVID-19 patients develops Long COVID, which is linked to SARS-CoV-2 persistence in the gastrointestinal tract, resulting in chronic inflammation and microbiota dysregulation. Given that gut microbiota dysbiosis plays a pivotal role in antiviral defense and gastrointestinal conditions, here we examine emerging evidence on how persistent SARS-CoV-2 infection may contribute to the aetiology of enteric disorders. In particular, we emphasise the intricate connection between chronic inflammation caused by persistent SARS-CoV-2 infection (e.g., irritable bowel syndrome and inflammatory bowel disease) and the possible development of diseases such as Crohn's disease and ulcerative colitis.},
}
@article {pmid41754542,
year = {2026},
author = {Puigdellívol-Sánchez, A and Arévalo-Genicio, A and García-Arqué, MC and Gragea-Nocete, M and Lozano-Paz, C and Moro-Casasola, V and Pérez-Díaz, C and Valls-Foix, R and Roca-Puig, R and Llistosella, M},
title = {Long COVID and Reduced Thrombosis in Antihistamine-Treated Patients: An Observational Study in the Metropolitan Area of Barcelona.},
journal = {Viruses},
volume = {18},
number = {2},
pages = {},
pmid = {41754542},
issn = {1999-4915},
support = {grant number PT-082023-EP subproject COVID-P.//GENERALITAT DE CATALUNYA/ ; },
mesh = {Humans ; Male ; Female ; Spain/epidemiology ; *COVID-19/epidemiology/complications ; *Histamine Antagonists/therapeutic use ; Aged ; Middle Aged ; *Thrombosis/epidemiology/prevention &amp; control ; Aged, 80 and over ; SARS-CoV-2 ; Incidence ; Adult ; COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Early evidence from a nursing home in Yepes (Toledo, Spain) indicated that antihistamines combined with azithromycin prevented deaths and hospitalizations during the first COVID-19 wave. Subsequent data from the Consorci Sanitari de Terrassa (CST) showed that patients chronically taking antihistamines had significantly reduced hospital admissions and mortality. However, a concerning rise in long COVID incidence (2-5%) after the third infection and a doubling of thrombosis rates in patients over 60 were observed.<br><br>OBJECTIVE: This study aimed to determine whether chronic antihistamine prescription is associated with a reduction in long COVID syndrome and thrombotic events.<br><br>METHODS: We analyzed anonymized data from the CST population (n = 192,651 as of March 2025). Variables included age, gender, chronic antihistamine use, number of chronic treatments (nT), COVID-19 vaccination status, SARS-CoV-2 infection history, long COVID (LC) incidence, and aggregated thrombotic events. Odds ratios (OR) were calculated using chi-square tests.<br><br>RESULTS: The prevalence of LC increased progressively with successive infections in the non-antihistamine group. No significant differences were found with the antihistamine group, which presented no LC cases among the 52 patients with three documented infections. Thrombotic events were significantly less frequent in antihistamine users with at least one chronic prescription (p < 0.0001).<br><br>CONCLUSIONS: Results suggest a protective effect of antihistamines against thrombotic events. While confirmation via multicenter, randomized trials is needed, a pragmatic approach using antihistamines could be considered for symptomatic patients in the early stage of infection.},
}
@article {pmid41753154,
year = {2026},
author = {Munguía, L and Silva, S and Villarreal, F and Nájera, N and Ceballos, G},
title = {Effects of Cacao Flavonoids in Long COVID-19 Patients with Chronic Fatigue: FLALOC, a Placebo-Controlled Randomized Clinical Trial.},
journal = {Journal of clinical medicine},
volume = {15},
number = {4},
pages = {},
pmid = {41753154},
issn = {2077-0383},
support = {SIP20240889 and SIP 20240919//Instituto Polit&#xe9;cnico Nacional/ ; },
abstract = {Background: In the context of long COVID, persistent fatigue is among the most prevalent symptoms that can develop after SARS-CoV-2 infection. Mitochondrial myopathy and endothelial dysfunction, which are triggers of inflammation, have emerged as prominent causes of long COVID-induced fatigue. Interestingly, the intake of flavanols, particularly (-)-epicatechin (EC), has been associated with the positive modulation of endothelial and mitochondrial structure and function. Methods: In this work, we conducted a randomized, double-blind, placebo-controlled clinical trial to determine whether an EC-enriched supplement (ECES) improves plasma markers of inflammation, endothelial structure, and fatigue-related endpoints in patients with long COVID-19. Results: The study included 46 subjects (mean age 52 years) who were instructed to consume two capsules/day for 90 days of either ECES (n = 23) or placebo (n = 23). Endpoints assessed included mean changes in plasma inflammatory markers (IL-1β, IL-6, and TNF-α) and endothelial dysfunction markers (syndecan-1), handgrip strength, fatigue scale, and quality of life (QoL). The results showed significant improvements in the ECES group for inflammatory markers, syndecan-1, and fatigue compared with the placebo group. Conclusions: The results yield intriguing positive findings for EC and open a new avenue for treating long COVID.},
}
@article {pmid41752954,
year = {2026},
author = {Morales-Vazquez, HN and Cardona-Müller, D and Grover-Paez, F and Ramos-Becerra, CG and Cardona-Muñoz, EG and Ramos-Zavala, MG and Carmona-Huerta, J and Hernandez-Del-Rio, JE and Miranda-Aquino, T and Gonzalez-Padilla, C and Lopez-Gradilla, CJ},
title = {Arrhythmias as Part of Long COVID Syndrome in Hospitalized Patients That Survived a Severe COVID-19 Infection and the Potential Protective Role of Metformin in These Patients.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {2},
pages = {},
pmid = {41752954},
issn = {2075-1729},
abstract = {BACKGROUND: Cardiac arrhythmias are a frequent complication of acute SARS-CoV-2 infection. However, their long-term prevalence and clinical determinants among patients with post-COVID-19 syndrome, especially those previously hospitalized, remain poorly defined.<br><br>OBJECTIVES: To assess the prevalence and types of arrhythmias in long COVID patients following hospitalization and to identify associated clinical risk factors.<br><br>METHODS: In this cross-sectional study, 53 patients previously hospitalized with confirmed COVID-19 were evaluated &#x2265;3 months post-infection. All participants underwent a standardized clinical assessment, 12-lead electrocardiography, and 24 h Holter monitoring. Logistic and Cox regression analyses were performed to identify predictors of arrhythmia.<br><br>RESULTS: Arrhythmias were identified in 41.5% (n = 22) of patients. Atrial fibrillation (32%) was the most frequent arrhythmia, followed by sinus bradycardia (27%) and sinus tachycardia (18%). Age (OR 1.06, 95% CI 1.01-1.10, p = 0.01) and length of hospital stay (OR 1.1, 95% CI 1.01-1.2, p = 0.04) were independently associated with arrhythmia. Biguanide (metformin) therapy was inversely associated with the occurrence of arrhythmia (Exp(B) = 0.017, p = 0.008). Dyspnea (82.4%) and palpitations (41.5%) were the most commonly reported symptoms.<br><br>CONCLUSIONS: Arrhythmias are common in patients with long COVID following severe disease. Advanced age and prolonged hospitalization are significant risk factors, while biguanide use may offer a protective effect. These findings underscore the need for targeted cardiac surveillance in this population.},
}
@article {pmid41751924,
year = {2026},
author = {Camici, M and Franco, M and Talamanca, L and Paulicelli, J and Scarnecchia, L and Petino, M and Mazzotta, V and Mastrorosa, I and Cimini, E and Tartaglia, E and Notari, S and Zuppi, P and Baldelli, R and Bocci, MG and Maggi, F and Girardi, E and Antinori, A},
title = {Prevalence of Circulating Autoantibodies Against G-Protein-Coupled Receptors as Potential Biomarkers for Long COVID: Preliminary Investigations.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41751924},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/blood ; Male ; *Autoantibodies/blood/immunology ; Female ; Middle Aged ; Biomarkers/blood ; *Receptors, G-Protein-Coupled/immunology ; SARS-CoV-2/immunology ; Aged ; Case-Control Studies ; Adult ; Prospective Studies ; },
abstract = {This prospective, single-center, case-control study investigated circulating autoantibodies (AAbs) targeting G protein-coupled receptors (GPCRs) in Long COVID (LC) patients to identify potential diagnostic biomarkers and therapeutic targets. Fifteen participants were enrolled at the LC clinic in Rome: eleven with severe LC-defined as >4 persistent symptoms (fatigue, cognitive impairment, poor exercise tolerance, dyspnea, arthralgia, or dysautonomic manifestations) >3 months post-infection-and four asymptomatic post-COVID (APC) individuals. Fatigue was assessed using the Fatigue Assessment Scale (FAS ≥ 22; severe ≥ 35). Auto-Abs against AT1R, endothelin receptor A, adrenergic (α1, α2, β1, β2), and muscarinic (M1-M5) receptors were quantified, along with blood cortisol and ACTH levels. SARS-CoV-2-specific T-cell responses to Spike and Nucleocapsid proteins were evaluated by ELISpot assay. In our small cohort, LC patients were younger, had fewer comorbidities (p = 0.03), fewer vaccine doses (p = 0.03), and higher FAS scores (33 vs. 12; p = 0.001). Mean GPCR AAbs levels were higher in LC than in APC (8.88 vs. 5.45 Units/mL; p = 0.17), indicating a coherent autoimmune signature in LC that correlates with symptom development. Morning cortisol was lower in LC (12.7 vs. 17 mg/dL; p = 0.01), and T-cell responses tended to be weaker. These findings suggest GPCR AAbs may serve as biomarkers and therapeutic targets for a subset of patients, guiding diagnosis and treatments with IV immunoglobulin or immunoadsorption.},
}
@article {pmid41751338,
year = {2026},
author = {Notarte, KI and Catahay, JA and Velasco, JV and Ver, AT and Lee, J and Rizk, JG and Lippi, G and Fernández-de-Las-Peñas, C},
title = {Complement System Dysregulation in the Immunopathogenesis of Long COVID: Systematic Evidence Synthesis.},
journal = {Biomedicines},
volume = {14},
number = {2},
pages = {},
pmid = {41751338},
issn = {2227-9059},
abstract = {Background/Objective: Long COVID is an important cause of disability following SARS-CoV-2 infection; yet, its underlying mechanisms are not completely understood. One proposed mechanism is the long-lasting dysregulation of the immune complement system. This systematic review is the first to summarize the current evidence and evaluate the potential role of long-lasting complement activation in people with long COVID. Methods: A systematic electronic search on PubMed, MEDLINE, CINAHL, and Embase was conducted up to 15 October 2025, to identify studies investigating complement activation in people with the post-COVID-19 condition. The Newcastle-Ottawa Scale was used to evaluate the risk of bias and methodological quality. Results: Among the 247 studies initially identified, eleven met the inclusion criteria, comprising 1435 individuals (age: 48.5 years, 70% females) with long COVID and 1124 controls (age: 43.6 years, 60% females). All studies were of a high quality, with scores ranging from 7 to 8 stars (mean: 7.6 ± 0.5). The activation of the classical complement pathway was investigated in nine studies, whereas the lectin, alternative, and terminal complement pathways were each assessed in three studies. Multiple studies investigated several complement pathways. The results were heterogeneous since several markers of complement activation spanning the classical (C2, C4a, C4b, and C1s-C1INH), alternative (Ba, iC3b, and Factor D), and terminal (C5bC6, C5a, C9, and TCC) pathways were elevated, whereas other markers were not significantly different (C3, C4, and C4d) between patients with/without long COVID. In addition, markers spanning the lectin complement pathway (MBL, and MASP1-C1INH) were not significantly different between individuals with and without long COVID. Conclusions: The current evidence suggests potential long-lasting complement system dysregulation in individuals with long COVID, although the clinical significance remains controversial, due to heterogenous findings. Specific post-COVID symptom clusters, such as fatigue, dyspnea, or brain fog, have been linked to a distinct pattern of complement dysregulation. Substantial methodological heterogeneity, including differences in follow-up periods, complement markers, assessment methods, and control groups, along with the small number of available studies, underscores the need for further research to clarify the mechanisms linking complement dysregulation to long COVID.},
}
@article {pmid41751249,
year = {2026},
author = {Daodu, LP and Raste, Y and Allgrove, JE and Arrigoni, FIF and Kayyali, R},
title = {Association Between COVID-19 Vaccination and Long COVID Symptoms in Hospitalised Survivors: Distinguishing Prevention from Reverse Causality.},
journal = {Biomedicines},
volume = {14},
number = {2},
pages = {},
pmid = {41751249},
issn = {2227-9059},
support = {KU-RCP10656/"Long COVID -Croydon//Croydon Health Services NHS Trust/ ; },
abstract = {Background: While COVID-19 vaccination significantly reduces acute disease severity, its impact on the incidence of long COVID remains debated, with some observational studies paradoxically suggesting higher symptom rates among vaccinated individuals. This study aimed to resolve this controversy by distinguishing between the protective effects of prior immunity and the confounding influence of reverse causality. Methods: We conducted a retrospective cohort study of 627 adults hospitalised for COVID-19 in London. Participants were stratified into two analytical cohorts based on vaccination timing: a "prevention cohort" (vaccinated ≥14 days pre-infection) and a "post-acute cohort" (vaccinated post-infection). Multivariable Bayesian logistic regression was employed to estimate Adjusted Odds Ratios (aOR) for long COVID, controlling for age, gender, BMI, comorbidities, and acute length of hospital stay (LoS). Results: In the prevention cohort, prior vaccination demonstrated a non-significant protective trend against long COVID (aOR 0.81; 95% CI 0.45-1.42; p = 0.45), with no significant difference observed between homologous and heterologous regimens. The post-acute cohort exhibited a strong, significant positive association (aOR 3.41; 95% CI 2.23-5.52; p < 0.001), indicating substantial indication bias, with symptomatic individuals more likely to seek vaccination. The strongest independent predictors of long COVID were comorbidities (aOR 2.78) and prolonged acute hospitalisation (≥4 days; aOR 1.82). Conclusions: Vaccination administered prior to infection demonstrates a protective trend against long COVID, whereas the strong association observed with post-infection vaccination reflects indication bias, with symptomatic survivors being more likely to seek immunisation. Clinical strategies to mitigate post-acute sequelae should prioritise reducing acute disease severity and managing comorbidities, which were identified as the dominant independent predictors of risk in hospitalised patients.},
}
@article {pmid41750353,
year = {2026},
author = {Makki, R and Kassem-Moussa, S and Al Nemer, F and El Majzoub, R and Fayyad-Kazan, H and Rachidi, W and Badran, B and Fayyad-Kazan, M},
title = {MicroRNAs in Long COVID: Key Regulators, Biomarkers, and Therapeutic Targets of Post-SARS-CoV-2 Sequelae.},
journal = {Biomolecules},
volume = {16},
number = {2},
pages = {},
pmid = {41750353},
issn = {2218-273X},
mesh = {Humans ; *COVID-19/genetics/complications/virology/metabolism ; *MicroRNAs/genetics/metabolism/blood ; Biomarkers/metabolism/blood ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is clinically defined by persistent symptoms that endure beyond acute infection and affect multiple organ systems, including the immune, cardiopulmonary, neurological, and metabolic axes. The underlying mechanisms remain poorly resolved, limiting the development of targeted diagnostics and therapeutics. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, control inflammatory networks, antiviral responses, mitochondrial bioenergetics, and fibrotic pathways, all of which are implicated in long COVID pathogenesis. Recent studies show durable changes in circulating miRNA signatures months after recovery from the acute phase, suggesting a role in maintaining chronic immune activation and metabolic dysfunction. Importantly, circulating miRNAs are stable, quantifiable in biofluids, and reflect systems-level dysregulation, positioning them as promising biomarker candidates for patient stratification, symptom clustering, and disease monitoring. Moreover, miRNA-directed interventions, such as mimics and antagomiRs, represent an emerging precision-medicine strategy to correct sustained molecular disturbances. This review summarizes current evidence linking miRNAs to long COVID, highlights their biomarker potential, and discusses therapeutic avenues that may help advance mechanism-based interventions for this globally emerging chronic condition.},
}
@article {pmid41750136,
year = {2026},
author = {Qazi, S and Shields, C and Cabrera, K and Nguyen, J and Donthineni, PR and Barthelemy, N and Gunawardene, A and Sepulveda-Beltran, P and Tamariz, L and Galor, A},
title = {Ocular Symptoms as a Marker of Dysautonomia in Long-COVID Patients: A Cross-Sectional Analysis.},
journal = {Brain sciences},
volume = {16},
number = {2},
pages = {},
pmid = {41750136},
issn = {2076-3425},
support = {UM SIP 2018-2R//University of Miami Interdisciplinary Team Science Award/ ; },
abstract = {Background/Objectives: Post-coronavirus syndrome (long-COVID) refers to a multi-systemic range of symptoms that follows acute SARS-CoV-3 infection. Long-COVID has been linked with autonomic neuropathy as well as dry-eye disease (DED), an umbrella term that includes a variety of ocular symptoms and signs. Despite these associations, little is known about the co-occurrence of DED and dysautonomia symptoms in individuals with long-COVID. This study aims to examine relationships between dysautonomia and ocular symptoms in a long-COVID patient population. Methods: Cross-sectional study of 162 veterans with long-COVID. The Composite Autonomic Symptom Score-31 (COMPASS-31) assessed dysautonomia symptoms, and the NASA lean test and heart-rate variability metrics captured dysautonomia signs. Dry-eye disease (DED) symptoms were measured with the 5-Item Dry-Eye Questionnaire (DEQ5) and the Ocular Surface Disease Index (OSDI), while ocular pain intensity and neuropathic pain descriptors were evaluated using a Numerical Rating Scale (NRS) and select questions from the Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), respectively. Results: Most participants (78%) reported DED symptoms (DEQ5 ≥ 6). Nearly all COMPASS-31 domains were associated with DED symptoms, with the strongest correlation observed between the OSDI and pupillomotor scores (r = 0.67, p < 0.001). Among the autonomic signs, the strongest associations were observed between the change in systolic and diastolic blood pressure from baseline to 8 min and ocular pain triggered by temperature (r = -0.44 and r = -0.48, respectively, p < 0.01 for both). On linear regression analyses, pupillomotor and secretomotor symptoms remained positively associated with DED symptoms, while autonomic signs were most closely related to ocular pain metrics, with fluctuating blood pressure changes during orthostasis relating to neuropathic symptoms. Conclusions: DED symptoms, including ocular pain intensity, relate to autonomic symptoms in a long-COVID cohort. While associations with autonomic signs were less consistent, these data suggest that subtle autonomic variability relates to ocular pain in the long-COVID setting.},
}
@article {pmid41749635,
year = {2026},
author = {Esposito, SMR and Maglietta, G and Campana, BR and Fainardi, V and Poeta, M and Zampogna, S and Colomba, C and Suppiej, A and Cardinale, F and Bosis, S and Castagnola, E and Midulla, F and Giaquinto, C and Giordano, P and Biasucci, G and Nunziata, F and Grandinetti, R and Condemi, A and Raiola, G and Guarino, A and Diodati, F and Caminiti, C and , },
title = {Phenotyping Pediatric Long COVID: Symptom Clusters from a Longitudinal Multicenter Italian Cohort.},
journal = {Children (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {41749635},
issn = {2227-9067},
abstract = {Background: The aim of this study was to identify patient clusters based on acute symptom profiles and individual characteristics most likely to develop pediatric post-acute sequelae of SARS-CoV-2 infection (PASC), as well as clusters among patients with PASC based on post-acute sequelae and associated characteristics. Methods: This multicenter cohort study in 12 Italian pediatric units enrolled patients aged 0-17 years within three months of a laboratory-confirmed SARS-CoV-2 infection. Participants who completed at least two surveys developed by the ISARIC over one year were analyzed. PASC was defined per WHO criteria. Multiple Correspondence Analysis and Hierarchical Clustering were performed. Results: Of 1137 children enrolled, 850 (76%) completed at least two surveys. The most prevalent age group was older children (6-11 years) (46%); adolescents (12-17) and young children (0-5) were numerically similar. Males were more represented (51.9%), except for the adolescent group (45.1%). PASC occurred in 32.8% of participants, with the distribution of sequelae types varying by age. Clustering in COVID-19 cases identified three clusters: young children mainly presented with respiratory symptoms and with a higher risk of hospitalization, while older children were spared in both acute and post-acute phases. Adolescents, particularly females, reported more pronounced acute symptoms and developed PASC more frequently. Clustering analysis of cases with PASC identified three clusters, confirming these age-related patterns. Young children still exhibited respiratory sequelae, and older children confirmed good recovery with minimal complications, while adolescents, especially females, remained the most affected subgroup, reporting persistent neuropsychological sequelae such as fatigue and insomnia. Conclusions: Findings support age-tailored follow-up, emphasizing respiratory monitoring for young children and targeted neuropsychological care for adolescents, particularly girls.},
}
@article {pmid41749262,
year = {2026},
author = {Odeh, A and Formanek, VL and Smith, C and Jha, N and Tajino, J and Lewis, JH and Gastineau, L and Patel, S and Zhao, S and Wei, L and Moberly, AC and Merfeld, DM and Simons, CT and Kobel, MJ and Zhao, K},
title = {Objective assessment of long-term impact of COVID-19 on multiple sensory functions.},
journal = {BMC medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41749262},
issn = {1741-7015},
support = {R01 DC020737/DC/NIDCD NIH HHS/United States ; R01 DC020737/DC/NIDCD NIH HHS/United States ; },
abstract = {BACKGROUND: This ongoing study investigates the impact of post-acute sequelae of SARS-CoV-2 infection (PASC) on broad sensory functions.<br><br>METHODS: Sixty subjects aged 27-78&#xa0;years were recruited who had contracted COVID-19 between 1/17/2020 and 12/21/2023 and had persistent symptoms (4.3-52.9, median&#x2009;=&#x2009;27.48&#xa0;months). Quantitative sensory assessments included (1) smell: 9-Item NIH toolbox odor identification, detection threshold to phenyl-ethyl alcohol, and retronasal candy test; (2) taste: modified NIH toolbox; (3) chemesthesis: nasal menthol lateralization thresholds and oral capsaicin identification; (4) hearing: pure-tone audiometry, otoacoustic emissions, words-in-noise recognition, and Dichotic Digits Test; (5) vestibular/balance: video head impulse testing, Subjective Visual Vertical, vestibular perceptual thresholds, and modified Romberg balance test; and (6) cognitive assessment: The Self-Administered Gero-Cognitive Exam, Digit Symbol Substitution Test, and Trail-Making Test.<br><br>RESULTS: Overall, subjects self-reported high and overlapping dysfunctions: 67.3% smell, 63.6% taste, 56.5% balance and dizziness, 31.8% auditory, and 51.3% brain fog or cognitive dysfunctions, with varying discrepancy to the measured and confirmed deficits (smell 65.5%, taste 16%, vestibular 31.6%, hearing 53.4%, and cognition 19.1%). Significant associations were found between confirmed vestibular and auditory impairments (p&#x2009;=&#x2009;0.04), and cognitive impairments with central components of vestibular (p&#x2009;=&#x2009;0.03) and auditory (p&#x2009;=&#x2009;0.01) impairments, but not with their peripheral components. Similarly, strong associations were found between identification components of smell and taste tests (p&#x2009;=&#x2009;0.003), which may involve more central processing, but not with threshold tests (a more peripheral process). Hospitalization significantly associated with smell (p&#x2009;=&#x2009;0.05), cognitive (p&#x2009;=&#x2009;0.009), vestibular (p&#x2009;=&#x2009;0. 001), and peripheral auditory (p&#x2009;=&#x2009;0.01) dysfunctions. Age significantly associated with auditory (p&#x2009;=&#x2009;0.02), vestibular (p&#x2009;=&#x2009;0.01) and central olfactory (p&#x2009;=&#x2009;0.03) dysfunctions.<br><br>CONCLUSIONS: COVID-19 impacts sensory systems broadly and differently, both peripherally and centrally, driven in part by aging, initial disease severity, and underlying post-COVID cognitive dysfunctions. Subjective symptoms may not always be corroborated by measured deficits.},
}
@article {pmid41745098,
year = {2026},
author = {Zoccali, F and Fratini, C and Pennacchia, F and Cascone, F and de Vincentiis, M and Petrella, C and Barbato, C and Minni, A},
title = {Hyperbaric Oxygen Therapy on Long COVID Symptoms: A Breath of Fresh Air.},
journal = {Diseases (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
pmid = {41745098},
issn = {2079-9721},
abstract = {Long COVID is defined as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanations", as reported by the World Health Organization. A growing number of people are dealing with a variety of lingering symptoms even after recovering from an acute infection. These can include fatigue, muscle pain, shortness of breath, headaches, cognitive issues, neurodegenerative symptoms, anxiety, depression, and a feeling of hopelessness, and therapeutic options for long COVID are investigated. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. The aim of this literature search is to analyze the state of the art of a potential role of HBOT to improve chronic fatigue, cognitive impairments and neurological disorders. A literature analysis was performed, focusing on the clinical efficacy of HBOT for treating long COVID symptoms. The results from January 2021 to October 2025, using a standard registry database, showed 21 studies, including one case report, ten randomized controlled trial, eight systematic reviews and three studies regarding the molecular mechanism and markers changing after HBOT. They suggested that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms and cardiopulmonary functions. HBOT is a safe treatment and has shown some benefits for long COVID symptoms. To precisely define indications, protocols, and post-treatment evaluations, we need to conduct more in-depth, large-scale studies.},
}
@article {pmid41742356,
year = {2026},
author = {Ogbu-Nwobodo, L and Hwong, AR and Murphy, K and Goldman, ML and Dilley, JW},
title = {Long COVID in Populations With Serious Mental Illness: Clinical and Policy Implications.},
journal = {Psychiatric services (Washington, D.C.)},
volume = {},
number = {},
pages = {appips20240457},
doi = {10.1176/appi.ps.20240457},
pmid = {41742356},
issn = {1557-9700},
abstract = {As the world recovers from the height of the COVID-19 pandemic with ongoing plans for a strengthened behavioral health infrastructure-from crisis services to long-term care-one of the health conditions that has emerged is long COVID. This multisystem condition is characterized by persistent symptoms that develop after the acute phase of COVID-19 infection. Although the full clinical and scientific understanding of long COVID's neuropsychiatric impact is still evolving, a sizable cohort of patients has emerged with various long-term and often confusing symptoms, which can include cognitive impairment, mood dysregulation (e.g., anxiety or depression), sleep disturbances, posttraumatic symptoms, and chronic fatigue. Recognizing long COVID's debilitating impact on quality of life and wide-ranging societal consequences, the authors sought to summarize current knowledge about long COVID among individuals with a preexisting serious mental illness and to propose care and treatment recommendations for clinicians and public policy makers.},
}
@article {pmid41741603,
year = {2026},
author = {Santos-de-Araújo, AD and de Oliveira Garcia, BR and Bassi-Dibai, D and Júnior, NFS and Ricci, PA and Camargo, PF and Marmorato, KTM and Phillips, SA and Arena, R and Borghi-Silva, A},
title = {A single bout of submaximal aerobic functional capacity test acutely promotes endothelial function in long COVID patients.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-41182-2},
pmid = {41741603},
issn = {2045-2322},
support = {24/22713-3//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
}
@article {pmid41740316,
year = {2026},
author = {Spedding, M and Aerts, J and Alexander, S and Bellozzi Woestelandt, AG and Chiricozzi, E and Henriques, A and Lledo, PM and Loeffler, JP and Perera, R and Platt, FM and Pradat, PF and Rene, F and Schapira, A and St Clair, L and Talbot, K and Taquet, M and Toborek, M and Turner, B and Zandi, M and Gressens, P},
title = {Links between COVID-19, long COVID, and neurodegeneration: The role of glycosphingolipids.},
journal = {Pharmacological reviews},
volume = {78},
number = {2},
pages = {100113},
doi = {10.1016/j.pharmr.2026.100113},
pmid = {41740316},
issn = {1521-0081},
abstract = {Glycosphingolipids (GSLs) play major roles in viral infections by mediating viral entry and egress from cells in lipid rafts; however, GSLs are also important in neurodegenerative diseases. The role of GSLs in acute COVID-19 infection is critical but remains less-studied in the sequelae of long COVID (post-COVID condition); because the same enzymes that regulate GSL metabolism are critical for viral entry and exit, neuromuscular junctions, neurological function, and cellular metabolism, it is important to determine whether long COVID may increase the risk of subsequent neurodegeneration. SARS-CoV-2 infection alters lipid metabolism and oxygen use and can bind to and modify the expression of neurotrophic GSLs such as GM1 ganglioside. GM1 (N-acetylneuraminic acid) is human-specific and probably evolved as a result of a pandemic 3-2.5 million years ago that drove its selection. GM1 functions as a coreceptor with angiotensin-converting enzyme 2 for SARS-CoV-2 while also being a neurotrophin. Viral multiplication takes place in the endoplasmic reticulum/Golgi apparatus, where GSLs are synthesized. This review defines the complex interaction between viruses, GSLs, and neurodegeneration, which provides new perspectives on the interlinked metabolic changes. A European working group has been set up to assess the risks of neurodegeneration with long COVID, based on potential GSL-mediated mechanisms. SIGNIFICANCE STATEMENT: The SARS-CoV-2 pandemic has resulted in a large number of subjects living with long-term consequences (long COVID). Glycosphingolipids and gangliosides are involved in both viral infections and neurodegeneration; hence, it is important to evaluate whether long COVID may increase the risk of neurodegeneration via this route. This study is the result of a European consortium formed to evaluate this possibility.},
}
@article {pmid41737593,
year = {2026},
author = {Thangaleela, S and Wang, CK},
title = {Impact of nutrition on long COVID.},
journal = {Sports medicine and health science},
volume = {8},
number = {2},
pages = {128-144},
pmid = {41737593},
issn = {2666-3376},
abstract = {Long COVID is characterized by a group of persistent symptoms following the acute SARS-COV2 infection, which presented a multifaceted challenge to the healthcare systems all over the globe. The long COVID symptoms span various organ systems including the respiratory, cardiovascular, gastrointestinal, and neurological manifestations. Mitochondrial dysfunction and immune dysregulation play crucial roles in the long COVID pathophysiology. Recently nutritional intervention gained much attention in managing post-viral syndromes. Effective interventions like supplementation of omega-3 fatty acid, macro and micro nutrients, and vitamins help to reduce systemic inflammation and counteract muscle wasting. Other approaches like nutritional recovery, dietetic interventions, continuous nutritional care post-hospital discharge, nutritional rehabilitation programs, whole-diet approaches like Mediterranean diet, plant-based diet, and caloric optimization, improve overall functional recovery. Physical activity and exercise regimes have been shown to improve fatigue, dyspnea, and cognitive function. Tailored exercise regimes may promote safe rehabilitation. Certain ineffective interventions, such as non-personalized approaches, high dose of antioxidants, use of herbal products that are not clinically validated need to be addressed. Dietary interventions such as personalized nutritional counseling have been demonstrated to improve physical performance in long COVID patients. Further research is needed to refine protocols and identify optimal combinations of dietary and movement-based therapies to support the recovery of long-COVID patients. This narrative review focuses on the ongoing researches that reveals the intricate relationship between nutrition and long COVID recovery and also establishes effective protocols for nutritional care.},
}
@article {pmid41737426,
year = {2026},
author = {Dalfardi, B and Abtahi, H and Edalatifard, M and Mozaffari, S and Rahimi, B and Roostaei, G and Khoshnam Rad, N},
title = {The Impact of COVID-19 on Obstructive Pulmonary Diseases: A Narrative Review of Long-Term Consequences and Vaccination Strategies.},
journal = {Health science reports},
volume = {9},
number = {2},
pages = {e71882},
pmid = {41737426},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: The COVID-19 pandemic has posed significant challenges for individuals with obstructive pulmonary diseases (OPDs), such as asthma and chronic obstructive pulmonary disease (COPD). Emerging evidence highlights the complex interplay between SARS-CoV-2 infection and OPDs, including increased risks of severe disease, long-term sequelae, and potential new-onset respiratory conditions. This narrative review synthesizes current knowledge on the pathophysiological mechanisms, clinical outcomes, and management strategies for COVID-19 in OPD patients, with a focus on long-term consequences and vaccination efficacy.<br><br>METHODS: A comprehensive literature search was conducted using PubMed, Embase, and Scopus (January 2020-June 2025). Inclusion criteria encompassed original studies, reviews, and meta-analyses examining COVID-19's impact on asthma or COPD, while non-English publications, animal studies, and case reports were excluded. Data were extracted and thematically synthesized to address acute outcomes, long COVID, vaccination, and therapeutic considerations.<br><br>RESULTS: Risk and Severity: COPD patients faced higher risks of severe COVID-19 (hospitalization, ICU admission, and mortality), while asthma phenotypes influenced outcomes (eosinophilic asthma conferred milder disease).Long COVID: Persistent respiratory symptoms (dyspnea and cough), fatigue, and cognitive dysfunction were prevalent in OPD patients, with new-onset asthma reported post-infection.Vaccination: mRNA vaccines significantly reduced severe outcomes in OPDs, though biologic therapies in asthma may attenuate immune responses.Treatment: Antivirals (e.g., nirmatrelvir-ritonavir) and corticosteroids were effective, but drug interactions (e.g., CYP3A4 inhibitors) required careful management.<br><br>CONCLUSION: COVID-19 exacerbates OPD-related morbidity, underscoring the need for tailored prevention (vaccination and early diagnosis) and multidisciplinary management. Future research should prioritize phenotype-specific therapeutic strategies and long-term surveillance to mitigate post-COVID sequelae in this vulnerable population.},
}
@article {pmid41736939,
year = {2026},
author = {Sharp, M and Jones, C and Marshall, ZA and Birkett, S and Cable, NT and Harwood, AE},
title = {Understanding the factors influencing participant engagement and adherence in exercise referral in the City of Manchester.},
journal = {BMJ open sport &amp; exercise medicine},
volume = {12},
number = {1},
pages = {e003157},
pmid = {41736939},
issn = {2055-7647},
abstract = {OBJECTIVES: To identify demographic, clinical, socioeconomic and referral-pathway determinants of engagement, early dropout and non-participation in a large metropolitan exercise referral scheme (ERS), and to assess whether machine learning (ML) methods provide additional explanatory value beyond conventional regression.<br><br>METHODS: This retrospective cohort study analysed data from 11&#x2009;909 adults (&#x2265;18 years) referred for ERS in Manchester, UK, between 27 January 2022 and 28 February 2025. Outcomes were programme adherence (completion of &#x2265;12 exercise sessions), early dropout and non-participation. Multinomial logistic regression was used to examine predictors of outcomes. ML methods, including Random Forest models and k-means clustering, were applied to assess predictive performance, rank feature importance and identify participant subgroups.<br><br>RESULTS: Of 11&#x2009;909 referrals, 34.6% completed the programme, 34.2% declined to participate and 8.0% left early. Younger age, higher neighbourhood deprivation and psychosocial referral reasons (eg, loneliness, long covid) were associated with lower completion. Participants referred through outreach/social prescribing pathways were substantially more likely to remain in an 'intends to participate' state rather than complete, compared with those referred through clinical pathways. Random Forest models demonstrated good predictive accuracy, with early engagement indicators and deprivation emerging as the strongest predictors. Clustering identified a high-risk subgroup characterised by younger age, higher deprivation and low early attendance.<br><br>CONCLUSIONS: Engagement and adherence in ERS were strongly shaped by early engagement, deprivation, age and referral pathways. ML methods identified high-risk subgroups and reinforced the importance of early attendance. Targeted early support and ML-informed risk indicators may improve retention, particularly among younger and more deprived participants.},
}
@article {pmid41736814,
year = {2026},
author = {Isangwe, S and Talbot, D and Coutu, MF and Canitrot, E and Décary, S and Falcone, EL and Ouakki, M and Latouche, P and Piché, A and Simard, M and Balem, M and De Serres, G and Carazo, S},
title = {Functional impact of long COVID among healthcare workers with comorbidities in Quebec, Canada: a cross-sectional study.},
journal = {BMJ public health},
volume = {4},
number = {1},
pages = {e004108},
pmid = {41736814},
issn = {2753-4294},
abstract = {INTRODUCTION: Long COVID is a frequent post-infectious chronic condition that impacts quality of life and work performance. Whether individuals with comorbidities experience a greater functional impact of long COVID is unknown. We evaluated the functional impact of long COVID among healthcare workers (HCWs) with chronic cardiovascular diseases, chronic respiratory diseases, obesity or a history of depression, and compared it with that of HCWs without comorbidities.<br><br>METHODS: We conducted a cross-sectional study in Quebec, Canada. We compared self-reported long COVID cases to COVID-19-infected controls without long COVID on work ability, work functioning, health-related absenteeism, dyspnoea-associated impairment and psychological distress among HCWs (a) with at least one of the four comorbidities, (b) with each of the four comorbidities and (c) without comorbidities. We used inverse probability of exposure and robust Poisson regressions to estimate adjusted prevalence differences (aPD) and prevalence ratios. Comorbidity data were obtained from the Quebec integrated chronic disease surveillance system.<br><br>RESULTS: A total of 3754 and 8439 HCWs with and without comorbidities, respectively, were included. Among HCWs with at least one of the four comorbidities, long COVID was associated with higher prevalence of low work ability (aPD=15%, 95% CI: 12% to 18%), low work functioning (aPD=27%, 95%&#x2009;CI: 22% to 31%), health-related long-term absenteeism (aPD=8%, 95%&#x2009;CI: 5% to 11%), dyspnoea-associated impairment (aPD=23%, 95%&#x2009;CI: 19% to 26%) and psychological distress (aPD=24%, 95%&#x2009;CI: 20% to 28%). aPDs were greater among HCWs with comorbidities than among those without for low work ability (p=0.013 for interaction), for low work functioning (p=0.034) and for dyspnoea-associated impairment (p<0.001).<br><br>CONCLUSION: Long COVID is associated with significant functional impairment among HCWs with pre-existing chronic conditions. HCWs with at least one of the four comorbidities experience lower work ability, lower work functioning and more dyspnoea-associated impairment compared with those without comorbidities.},
}
@article {pmid41736389,
year = {2026},
author = {Rayner, C and Smith, N and Milne, R and Mir, G and de Kock, J and Bakerly, ND and , },
title = {'What Do People With Long Covid Want From Healthcare Services?' A Qualitative Exploration From Lived Experience.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70607},
pmid = {41736389},
issn = {1369-7625},
support = {//National Institute for Health and Care Research/ ; },
mesh = {Humans ; Qualitative Research ; *COVID-19/therapy/psychology ; Female ; United Kingdom ; *Health Services Accessibility ; Male ; Middle Aged ; Adult ; Interviews as Topic ; Aged ; SARS-CoV-2 ; Chronic Disease ; Delivery of Health Care ; },
abstract = {BACKGROUND: Long COVID (LC) is a chronic, multisystem condition affecting millions globally, with significant personal, social and economic consequences. Despite increasing recognition of its impact, healthcare services for LC remain inconsistent with patients frequently encountering fragmented services, scepticism and delays leading to patient-voiced frustration. Therefore, understanding patient priorities is crucial for optimising service provision.<br><br>OBJECTIVES: To explore what individuals with LC want from healthcare services-drawing on their lived experience and collaborative insights with clinicians and researchers, to inform principles for improving care delivery, barriers to access, expectations for service improvement, and the role of multidisciplinary care in managing LC.<br><br>METHODS: A qualitative study using thematic analysis was conducted, incorporating multiple data sources, including semi-structured interviews, workshops, and a patient-led audit. Key themes were identified, focusing on healthcare access, clinical assessments, treatment options, and service organisation.<br><br>STUDY PARTICIPANTS: Twenty-seven LC sufferers from the LOCOMOTION Patient Advisory Group (PAG) and Patient Advisory Network (PAN), along with clinicians and researchers involved in LC service provision across the United Kingdom, participated in the study.<br><br>RESULTS: Three major themes emerged: (1) Who the services are for: Equity of access for all those with LC. Barriers such as stigma, inequitable access and lack of clinician awareness need to be addressed. (2) What services should do: Consistent and standardised assessments and diagnostic clarity-particularly for modifiable conditions like autonomic dysfunction-and an emphasis on the need for early medical intervention, not just rehabilitation. (3) How services should operate: Care should be coordinated, proactive and adaptable to evolving evidence. Patients should not be discharged without ongoing review. Multidisciplinary collaboration should be patient-centred and informed by up-to-date research.<br><br>CONCLUSIONS: LC services should be designed to provide equitable, standardised and evidence-based care. Early intervention, appropriate medical testing and sustained follow-up are critical to improving patient outcomes. Patients emphasised the importance of being heard and the value of receiving timely care that reflects the latest scientific understanding and recognises their condition as real, treatable and deserving of ongoing clinical attention. Incorporating these insights into healthcare design may improve outcomes, service efficiency and trust between patients and providers.<br><br>Patients led all phases of this study, including design, analysis and writing, through active co-production with the LOCOMOTION research team. The paper was born out of discussions within the LOCOMOTION study's Patient Advisory Group (PAG). It was taken forward by C.R., N.S. and R.M., all members of the PAG, working closely with N.B., H.d.K. and G.M.},
}
@article {pmid41735088,
year = {2026},
author = {Yu, T and Wang, L},
title = {Commentary on 'Prevalence and trajectories of post-COVID-19 neuromuscular conditions: A systematic-review and meta-analysis'.},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125799},
doi = {10.1016/j.jns.2026.125799},
pmid = {41735088},
issn = {1878-5883},
}
@article {pmid41734323,
year = {2026},
author = {Löwy, I},
title = {[Long Covid: a long story].},
journal = {Medecine sciences : M/S},
volume = {42},
number = {2},
pages = {187-193},
doi = {10.1051/medsci/2026017},
pmid = {41734323},
issn = {1958-5381},
mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Psychophysiologic Disorders/psychology/diagnosis/etiology ; Chronic Disease ; },
abstract = {Patients with long Covid experience multiple, often very debilitating symptoms, yet their test results frequently appear normal. In the absence of objective indicators of a recognized disease, some professionals may conclude that the patient is suffering from a psychosomatic disorder. These patients face an epistemic injustice, that is, a failure to recognize their suffering as real. This injustice is rooted in a longstanding history of medically invisible disorders, which are diagnosed mainly on the basis of the patient's own narrative. The difficulties experienced by patients with long Covid cannot be dissociated from this history.},
}
@article {pmid41734322,
year = {2026},
author = {Gougeon, ML and Salmon, D},
title = {[Long COVID].},
journal = {Medecine sciences : M/S},
volume = {42},
number = {2},
pages = {185-186},
doi = {10.1051/medsci/2026016},
pmid = {41734322},
issn = {1958-5381},
}
@article {pmid41734308,
year = {2026},
author = {Rosenthal, E and Lert, F and Yazdanpanah, Y},
title = {[Long Covid: how to prevent, treat and advance research?].},
journal = {Medecine sciences : M/S},
volume = {42},
number = {2},
pages = {117-119},
doi = {10.1051/medsci/2026022},
pmid = {41734308},
issn = {1958-5381},
}
@article {pmid41732704,
year = {2026},
author = {Chen, Z and Li, B and Chen, Y and Liu, J and Luo, F and Ogunyemi, KO and Ge, Y and Ke, Y and Yang, Y and Chen, X and Shen, Y and , },
title = {Mapping spatial and social inequities of long COVID across the United States: a retrospective cohort study.},
journal = {Lancet regional health. Americas},
volume = {56},
number = {},
pages = {101401},
pmid = {41732704},
issn = {2667-193X},
abstract = {BACKGROUND: Long COVID affects a substantial portion of the U.S. population. The emergence of the Omicron variant and persistent sociodemographic disparities may contribute to temporal and regional variation in long COVID risk. However, such spatiotemporal variation and related social determinants remain poorly characterized. This study aimed to examine spatiotemporal patterns of county-level long COVID incidence and to identify sociodemographic factors associated with these patterns before and after the emergence of the Omicron variant.<br><br>METHODS: This retrospective study utilized data from the National COVID Cohort Collaborative (N3C), covering 5,652,474 COVID-19 cases from 2020 to 2024 and 41,694 long COVID cases across 1063 U.S. counties from 2021 to 2024. Temporal patterns of long COVID were analyzed before and after the Omicron variant's emergence, and spatial patterns were assessed using Moran's I and Getis statistics. Bayesian spatial random effect models were employed to evaluate the associations between long COVID incidence and sociodemographic factors such as economic vulnerability, healthcare access, and mobility.<br><br>FINDINGS: Among 4,070,879 COVID-19 cases analyzed, quarterly long COVID incidence ranged from 0.015% to 14.29%. Before the emergence of the Omicron variant, incidence was 204 cases per 10,000 COVID-19 cases, compared with 248 cases per 10,000 COVID-19 cases after Omicron emergence (p < 0.001). Based on the Local Moran's I statistic, 48.8% (328 of 673) of counties showed significant spatial correlation (p < 0.05) after Omicron's emergence, up from 43.5% (293 of 673) prior. High-risk areas became more concentrated in inland regions, while low-risk areas clustered along the East Coast. Long COVID incidence was significantly associated with economic vulnerability, limited healthcare access, and mobility constraints, with these sociodemographic disparities consistently driving its spatial disparities over time. Subregional analyses revealed distinct regional differences in social drivers.<br><br>INTERPRETATION: These findings highlight pronounced spatiotemporal and regional disparities in long COVID incidence across the United States. Targeted public health interventions, particularly in economically and geographically vulnerable regions, are essential to ensure equitable access to diagnosis, care, and resource allocation.<br><br>FUNDING: National Center for Advancing Translational Sciences; National Institutes of Health; National Science Foundation.},
}
@article {pmid41732619,
year = {2026},
author = {Manoukian, G and Kundukulam, S and Asatorian, G and Johnson, DM and Masood, MH and Venugopal, A and Manoukian, M and Aswathappa, S},
title = {Post-COVID Syndrome in Patients With Comorbid Hypertension or Diabetes: A Narrative Review of Long-Term Outcomes.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e102117},
pmid = {41732619},
issn = {2168-8184},
abstract = {Post-COVID syndrome (PCS), or long COVID, refers to a cluster of enduring symptoms that extend beyond the acute phase of the initial SARS-CoV-2 infection. Acute infection predominantly impacts the respiratory tract, but there is growing evidence for the multisystem involvement, such as cardiovascular, metabolic, and neurological, to be responsible for the prolonged presentation in PCS. Underlying cardiometabolic vulnerability may contribute to a high degree of susceptibility in patients with comorbidities like hypertension (HTN) and diabetes mellitus (DM). This narrative review summarizes current literature regarding PCS in patients with HTN and/or DM, focusing on proposed pathophysiological mechanisms, clinical manifestations, and reported long-term outcomes. In these populations, PCS has been linked across studies to processes including endothelial dysfunction, chronic low-grade inflammation, autonomic imbalance, and potential dysregulation of the renin-angiotensin-aldosterone system (RAAS). Persistent cardiovascular, metabolic, and neurocognitive symptoms are reported, but the magnitude and patterns of risk vary across studies, while comparative findings across HTN and DM remain heterogeneous. Symptoms reported frequently include fatigue, cognitive impairment ("brain fog"), and psychological distress, supporting the multisystem complexity of PCS. Although, previous work has indicated that cardiometabolic comorbidities could interact and moderate PCS severity and persistence, there is an important shortfall of both causality and prognosis, as well as the management of PCS. Longitudinal studies are needed for future research regarding risk stratification, disease course, and targeted interventions in individuals with PCS with comorbid high blood pressure and diabetes.},
}
@article {pmid41732199,
year = {2026},
author = {Smith, AB and Greenwood, DC and Milne, R and Ormerod, M and Sivan, M},
title = {The EQ-5D-5L and Minimal Important Change in Long COVID.},
journal = {Advances in rehabilitation science and practice},
volume = {15},
number = {},
pages = {27536351261423961},
pmid = {41732199},
issn = {2753-6351},
abstract = {INTRODUCTION: The EQ-5D-5L is the most commonly used patient-reported outcome measure in Long COVID (LC). Despite its frequent use, there have been few studies reporting LC-specific metrics to identify and interpret meaningful change. The aim of the study was therefore to determine the Minimal Clinically Important Difference (MCID) and Minimal Important Difference (MID) measures for the EQ-5D-5L in LC.<br><br>METHODS: Data were collected from a national study (LOCOMOTION) evaluating LC services in the UK, involving participants completing the EQ-5D-5L on at least 2 occasions. The EQ-5D domains were categorised using Paretian classification of health states, and the probability of superiority was used to determine changes in health states over time. EQ-5D-5L profile scores were converted into health utilities using the UK-specific algorithm. The MCID was derived using 0.5 standard deviation and the MID by a 0.2 effect size.<br><br>RESULTS: A total of 423 people (283 females, 67%) with LC completed the EQ-5D at 2 time points (median time interval: 196&#x2009;days). Most participants reported problems in at least 1 EQ-5D domain. Only around 25% of participants noted some improvement. The MCID estimates were 0.11 for the EQ-5D-5L and 10.6 for the EQ-5D-5L VAS. The MID for the EQ-5D-5L was 0.03. Some differences in the change metrics were observed depending on baseline health states and timing of the follow-up assessment.<br><br>CONCLUSION: Long COVID specific estimates of the MCIDs and MIDs were derived for the EQ-5D-5L and EQ-5D VAS. The MCIDs will facilitate the evaluation and interpretation of meaningful change in patient health states in LC, both at the individual level and more broadly in health economic assessments of LC management, intervention and rehabilitation programmes.},
}
@article {pmid41730996,
year = {2026},
author = {Doni Jayavelu, N and Samaha, H and Wimalasena, ST and Hoch, A and Gygi, JP and Gabernet, G and Ozonoff, A and Liu, S and Milliren, CE and Levy, O and Baden, LR and Melamed, E and Ehrlich, LIR and McComsey, GA and Sekaly, RP and Cairns, CB and Haddad, EK and Schaenman, J and Shaw, AC and Hafler, DA and Montgomery, RR and Corry, DB and Kheradmand, F and Atkinson, MA and Brakenridge, SC and Agudelo Higuit, NI and Metcalf, JP and Hough, CL and Messer, WB and Pulendran, B and Nadeau, KC and Davis, MM and Geng, LN and Fernandez Sesma, A and Simon, V and Krammer, F and Kraft, M and Bime, C and Calfee, CS and Erle, DJ and Langelier, CR and , and Guan, L and Maecker, HT and Peters, B and Kleinstein, SH and Reed, EF and Augustine, AD and Diray-Arce, J and Becker, PM and Rouphael, N and Altman, MC},
title = {Author Correction: Machine learning models predict long COVID outcomes based on baseline clinical and immunologic factors.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
doi = {10.1038/s43856-026-01425-9},
pmid = {41730996},
issn = {2730-664X},
}
@article {pmid41730994,
year = {2026},
author = {Strasser-Kirchweger, B and Kutil, RH and Zimmermann, G and Borgelt, C and Trutschnig, W and Hutzler, F},
title = {Machine-actionable criteria chart the symptom space of mental disorders.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02451-6},
pmid = {41730994},
issn = {2398-6352},
support = {20102-F2101312-FPR//Salzburger Landesregierung/ ; 20102-F2101312-FPR//Salzburger Landesregierung/ ; 20102-F2101312-FPR//Salzburger Landesregierung/ ; 20102-F2101312-FPR//Salzburger Landesregierung/ ; 20102-F2101312-FPR//Salzburger Landesregierung/ ; 20102-F2101312-FPR//Salzburger Landesregierung/ ; },
abstract = {Diagnostic rules are codified in consensus manuals such as DSM-5, yet they remain written in narrative form and cannot be computationally interrogated. Here, a deterministic framework is presented that translates diagnostic criteria into a machine-actionable representation of the full symptom space, which can be charted, navigated, and systematically analyzed. Unlike probabilistic models that infer patterns from large textual corpora, this framework directly interrogates explicit consensus criteria, providing a transparent and reproducible means of assessing conceptual coherence. Its potential is demonstrated by charting schizophrenia-spectrum disorders, which remain conceptually distinct despite substantial symptom overlap, and by evaluating the current National Academies' definition of Long COVID, which is largely subsumed by depressive and anxiety disorders. By making diagnostic consensus computable, the framework provides a reproducible foundation for evaluating delineation properties of existing and candidate diagnostic constructs and for developing interpretable, regulatory-compliant diagnostic support tools.},
}
@article {pmid41729896,
year = {2026},
author = {Elgner, M and Binneböse, M and Großmann, J and Frank, T and Bruckmann, P and Lahmann, C and Giel, KE and Allwang, C and Junne, F and Wallis, H},
title = {How to cope with Long COVID - A qualitative interview study on stressors and coping strategies of people affected by long-term consequences of COVID-19.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0343115},
pmid = {41729896},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; *Adaptation, Psychological ; Female ; Male ; Middle Aged ; *Stress, Psychological/psychology ; Adult ; Aged ; Quality of Life ; Qualitative Research ; SARS-CoV-2/isolation &amp; purification ; Pilot Projects ; Coping Skills ; },
abstract = {Long COVID, a multi-system-disease characterized by persistent somatic and mental symptoms following a SARS-CoV-2 infection, can severely impair health and quality of life of those affected. In the absence of adequate therapeutic approaches and a fragmented care landscape, our focus is on identifying individual stressors, the resulting needs and strategies people use to cope with the ongoing burden of the disease and its long-term stressors. This qualitative interview study is part of a pilot multicenter study addressing psychosocial needs in patients with Long COVID. The surveyed sample (n = 40) consists of affected people, who suffer from persistent symptoms and psychosocial stress after a SARS-CoV-2 infection. Based on the Transactional Stress Model according to Lazarus and Folkman and the Brief COPE by Carver, the qualitative analysis of semi-structured interviews focused on the various and individual coping attempts of the interviewees. Participants reported a wide range of persistent physical and mental complaints. Fatigue-associated complaints, cognitive impairments, fears and worries were mentioned frequently and perceived as particularly stressful. Job insecurity and financial worries, lack of recognition, stigmatization, lack of treatment and therapy approaches, withdrawal and social isolation were reported as stressors. In most cases, we identified an interplay between emotion-oriented (such as emotional support, self-care and positive thinking) and problem-oriented coping strategies (such as planning/pacing, self-help, withdrawal and avoidance). Emotional support as the most frequently mentioned strategy and as a fundamental resource in coping with this disease should be strengthened. These findings offer a valuable insight into the diverse stressors and coping patterns in dealing with post-viral symptoms of COVID-19. The analysis reveals that complaints and attempts to cope vary significantly among the participants. This underlines the importance of providing tailored support to those affected to help them manage their symptoms, improve their quality of life and enable them to participate in social life again.},
}
@article {pmid41728426,
year = {2026},
author = {Christoforou, ME and van Campen, LC and Visser, FC and Lee, CK and Lemmon, SL and Rowe, PC and Azola, AM},
title = {A Continuous Oral Regimen of High-Dose Cromolyn Sodium Is Effective for Some Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients With Mast Cell Activation Syndrome.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e102064},
pmid = {41728426},
issn = {2168-8184},
abstract = {Our clinical experience in the last four years using oral cromolyn in patients with mast cell activation syndrome (MCAS) suggests that a continuous oral regimen of high-dose cromolyn may enhance compliance with the medication. The five patients described in this retrospective case series were given instructions to take oral cromolyn using a continuous dosing regimen, placing the entire day's dose in an opaque bottle that is then filled with water, and sipping the solution throughout the day. If a conventional maximum dose of eight vials daily (800 mg) was tolerated but ineffective after a week, the patients were instructed to increase to 1600-2400 mg daily until reaching an optimal effect. We report that a cromolyn dose of 1600-2400 mg daily, administered using the continuous oral dosing regimen during the day, was effective in controlling signs and symptoms of mast cell activation. All five patients benefitted from a dose of cromolyn that is higher than usual and customary recommendations, but within the safety guidelines of the original Food and Drug Administration (FDA) application. The continuous oral regimen has some theoretical advantages over four discrete doses per day, though further study is needed.},
}
@article {pmid41727490,
year = {2026},
author = {Miano, L and Sinopoli, E and Cherubini, A and Suffritti, C and Pelusi, S and Rahmeh, F and Lamorte, GE and Peyvandi, F and Blasi, F and Grasselli, G and Bandera, A and Gualtierotti, R and Prati, D and Valenti, LVC},
title = {Association of SARS-CoV-2 infection with long-lasting increase in circulating IL-32 levels.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1739258},
pmid = {41727490},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/blood/immunology/epidemiology ; Male ; Female ; *Interleukins/blood ; Middle Aged ; *SARS-CoV-2/immunology ; Retrospective Studies ; Adult ; Biomarkers/blood ; Aged ; },
abstract = {BACKGROUND &amp; AIMS: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has a wide spectrum of clinical presentations ranging from asymptomatic viral replication to hyper-inflammatory syndrome and respiratory failure and can trigger immune disorders and long-COVID. Interleukin-32 (IL-32) is a pro-inflammatory cytokine induced during viral infections and chronic pulmonary disease.<br><br>AIM: Aim of this study was to investigate the impact of the SARS-CoV-2 pandemic and severe COVID-19 on circulating IL-32 levels.<br><br>STUDY DESIGN: Observational retrospective biomarker study.<br><br>PATIENTS &amp; METHODS: We analyzed 949 healthy blood donors (pre-pandemic and pandemic-era) and 212 patients hospitalized due to severe COVID-19 during the first five infection waves. IL-32 levels were measured by ELISA.<br><br>RESULTS: Pandemic-era blood plasma donors showed a +0.78 &#xb1; 0.09 log10 pg/ml mean increase in IL-32 (pandemic-era 2.91 &#xb1; 0.05 vs. pre-pandemic 2.14 &#xb1; 0.07 log10 pg/ml, p<0.0001). COVID-19 patients exhibited a similar elevated IL-32 compared to unexposed controls (+0.29 &#xb1; 0.11 log10 pg/ml, p=0.016; 2.43 &#xb1; 0.08 hospital admission vs. pre-pandemic). Among patients, mean IL-32 was higher in first-wave patients (2.68 &#xb1; 0.11 log10 pg/ml) than later waves (2.12 &#xb1; 0.11 log10 pg/ml). In setting of severe COVID-19, IL-32 levels were associated with corticosteroids administration (estimate1.99 &#xb1; 0.50; p<0.0001), whereas decreased during the later waves of infection (-0.56 &#xb1; 0.16; p=0.0005) and with age (estimate -0.01 &#xb1; 0.01; p=0.020). No links were found with sex, Intensive care unit admission, comorbidities, or mortality. A subset of the COVID patient cohort was tested for pro-inflammatory biomarkers: IL-32 displayed an inverse correlation with patients' neutrophil-to-lymphocyte ratio (NLR) (estimate -0.23 &#xb1; 0.81; p=0.005) and not with IL-6 and biomarkers of endothelial dysfunction (n=42, p=NS). In patients with available follow-up (n=96), IL-32 remained stable up to one-year post-discharge (+0.03 &#xb1; 0.12 log10 pg/ml, p=0.970; 2.55 &#xb1; 0.15 hospital admission vs. follow-up 3-12 months 2.58 &#xb1; 0.15 log10 pg/ml).<br><br>CONCLUSIONS: IL-32 levels increased following COVID-19, especially during the initial severe wave, and correlated with some markers of inflammation. IL-32 remained elevated up to one-year post-discharge, suggesting ongoing inflammation and supporting its potential as a biomarker for long-term sequelae.},
}
@article {pmid41727403,
year = {2025},
author = {Watson, LS and Toubouti, Y and Gray, SM and Guillén, N and Pérez-Millan, A and Rami, L and Sanchez-Valle, R and Johannesen, JK},
title = {Evaluating contributions of neuropsychological, psychiatric, and inflammatory processes to the expression of cognitive symptoms in post-acute COVID-19 syndrome.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1668380},
pmid = {41727403},
issn = {1664-0640},
abstract = {INTRODUCTION: Post-acute COVID-19 syndrome (PACS) has been widely associated with cognitive symptoms, however, the nature and severity of effects on cognitive function have been difficult to establish amid other aspects of PACS symptomatology. The current study used a regression modeling approach to parse unique and combined contributions of neuropsychological test performance, psychiatric symptoms, and inflammatory cytokine levels in predicting cognitive symptom severity, as measured by questionnaire responses from patient and observer perspectives.<br><br>METHODS: Forty-one patients presenting to a university medical center neurology clinic with cognitive complaints &#x2265;&#x2009;4 months after COVID-19 symptom onset were included in the analysis.<br><br>RESULTS: Although pre-morbid cognitive status was estimated to be at or above-average across participants, nearly 50% performed below expectation on three or more neuropsychological tests. Subjective Cognitive Decline Questionnaire (SCD-Q) ratings were clinically elevated, both from patient (MyCog) and observer (TheirCog) perspectives, yet bivariate relationships with neuropsychological and other measures of PACS symptomatology were non-significant. When combined in regression models, 36% of variance in MyCog score was explained by measures of anxiety, premorbid intelligence, and current neuropsychological test performance. TheirCog scores were explained by a unique set of neuropsychological tests, accounting for 33% of variance cumulatively. Measures of depression, fatigue, and inflammatory cytokines concentrations did not enter either model.<br><br>DISCUSSION: Taken together, cognitive sequelae of PACS appear to be rooted in changes in brain function that are detectable by objective neuropsychological testing. Although comorbidities associated with PACS can contribute to the experience of cognitive symptoms, we find cognitive symptoms, whether self-reported or observed, to be more directly associated with neuropsychological test performance than ongoing fatigue, psychiatric symptoms, or inflammatory processes.},
}
@article {pmid41726954,
year = {2026},
author = {Toppa, PH and Rushmore, RJ and Haggerty, K and Papadimitriou, G and Dougherty, D and Kubicki, M and González-Mora, JL and Pallanti, S and Castañeyra-Perdomo, A and Yeterian, E and Makris, N},
title = {Neuroanatomy of substantia nigra and ventral tegmental area dopaminergic, and dorsal raphe serotonergic circuits in the human brain using T1-weighted and diffusion magnetic resonance imaging: A morphometric pilot study with estimate of reliability.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.12.705574},
pmid = {41726954},
issn = {2692-8205},
abstract = {INTRODUCTION: We present here a methodology for morphometric analysis of the substantia nigra (SN), the ventral tegmental area (VTA), the dorsal raphe nucleus (DRN) and their respective structural brain circuits.<br><br>METHODS: Our analyses were based on multimodal T1-weighted MRI and diffusion MRI (dMRI) segmentation and tractography in 12 human subjects drawn from the Human Connectome Project (HCP) repository.<br><br>RESULTS: We were able to demonstrate strong connections of the SN, VTA and DRN with several brain regions, in particular the dorsolateral prefrontal cortex (DLPFC) and the cerebellum. More specifically, we created comprehensive visualizations of the SN and VTA dopaminergic as well as the DRN serotonergic structural circuits in the human brain, which, although preliminary, demonstrate the potential of multimodal neuroimaging to investigate these circuits quantitatively in clinical conditions. Finally, we created a pilot dataset for the most frequently observed structural connections, specifically those that were present more than 92% of the time among all subjects. Discussion This pilot morphometric report examines the structural circuits of the SN, VTA and DRN, which are critically involved in several biobehaviors and clinical conditions such as addiction, stress, Parkinson's disease (PD), schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, mood disorders, COVID-19 and long COVID. Importantly, the strong structural connectivity of the DLPFC and cerebellum with the SN, VTA and DRN is expected to be a potential target of noninvasive neuromodulation treatments in neuropsychiatry. Our findings demonstrate the potential of current clinical multimodal neuroimaging to delineate the dopaminergic (DA) and serotonergic (5-HT) circuits in the human brain in clinical conditions.},
}
@article {pmid41725650,
year = {2026},
author = {Ertzgaard, P and Wärdig, A and Duchen, K and Angelhoff, C},
title = {Psychosocial impact of pediatric long COVID: a dyadic analysis of persistent symptoms, sleep, and self-esteem in parents and children.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1769305},
pmid = {41725650},
issn = {1664-1078},
abstract = {BACKGROUND: Pediatric long COVID can lead to persistent symptoms that affect the child's daily functioning and may influence family dynamics. Parents of children with chronic conditions may be at risk of experiencing challenges related to their own health, sleep, and self-esteem. Exploring the parent-child dyad may provide a deeper understanding of how long COVID impacts both individuals and their relationship. The aim of this study was to describe health, sleep quality, insomnia symptoms, and self-esteem in parents of children with long COVID, and to see how these factors are affected by the child´s disability exploring child-parent dyads and triads.<br><br>METHODS: This cross-sectional study, part of the interdisciplinary project POCOKIDS, included 35 parents and 26 children who completed questionnaires on long COVID symptoms, sleep quality, insomnia, and self-esteem.<br><br>RESULTS: Parents with persistent symptoms reported poorer sleep, higher insomnia scores, and greater worry about finances, employment, social life, and their child's education than those without symptoms. Notably, parents without persistent symptoms reported lower self-esteem. Most children reported poor sleep quality, and nearly half met criteria for insomnia symptoms, with girls experiencing more sleep-related difficulties than boys. Children's self-esteem was less affected than their parents'.<br><br>DISCUSSION: The findings reveal a shared psychosocial burden and underscore the need for individualized support addressing both children's and caregivers' health and emotional needs.},
}
@article {pmid41722813,
year = {2026},
author = {Smadja, DM and Günther, S and Rancic, J and Lellouch, AG and Renaud, B and Diehl, JL and Philippe, A},
title = {Soluble ST2 fails to reflect persistent endothelial dysfunction or symptoms in post-acute sequelae of COVID-19.},
journal = {Annales pharmaceutiques francaises},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pharma.2026.02.008},
pmid = {41722813},
issn = {2772-803X},
abstract = {BACKGROUND: Soluble ST2 (sST2), the circulating decoy receptor of interleukin-33 (IL-33), has been validated as a prognostic biomarker of disease severity and vascular injury during acute COVID-19. However, its relevance in the context of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) remains unclear.<br><br>METHODS: We analyzed the association between plasma sST2 concentrations and clinical or vascular features in a prospective cohort of 137 long COVID patients (median age: 55 years; 49.6% male), encompassing 194 follow-up visits conducted 3 to 24 months after infection. Fatigue and dyspnea were systematically assessed, alongside full pulmonary function testing (PFTs), including diffusing capacity of the lung for carbon monoxide (DLCO). Plasma concentrations of sST2, VEGF-A, von Willebrand factor antigen (VWF: Ag) and circulating endothelial cells (CECs) were measured.<br><br>RESULTS: sST2 concentrations were significantly elevated in hospitalized patients during the acute phase of COVID-19 compared to healthy controls (P<0.001), but returned to baseline concentrations during the post-acute phase and remained stable across follow-up timepoints (3, 6, 12, and 24 months; P=0.11). sST2 was not associated with initial COVID-19 severity (P=0.13), nor with persistent symptoms including fatigue (P=0.11) or dyspnea (P=0.49), or with reduced DLCO (P=0.32) or abnormal PFTs (P=0.55). No correlation was found with VEGF-A, CECs, VWF: Ag, or D-dimers.<br><br>CONCLUSION: Although sST2 is a robust biomarker of acute COVID-19 severity, it does not reflect persistent endothelial dysfunction or symptom burden in long COVID. These findings suggest IL-33/sST2-independent mechanisms may underlie chronic vascular injury in PASC.},
}
@article {pmid41722320,
year = {2026},
author = {Alves Costa Silva, C and Pinheiro Bomfim, A and Dutra Medeiros, J and de Jesus Silva, J and Cazé-Ceron, AB and Cerqueira-Silva, T and Khouri, R and Barral, A and Barral-Netto, M and da Rocha Fernandes, G and Gomes Barbosa, C and S Boaventura, V},
title = {Corrigendum to "Nasal microbiota and clinical features in acute flu-like illness: COVID-19 status and long COVID follow-up" [International Journal of Infectious Diseases 162 (2026) 108196 https://doi.org/10.1016/j.ijid.2025.108196].},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {165},
number = {},
pages = {108441},
doi = {10.1016/j.ijid.2026.108441},
pmid = {41722320},
issn = {1878-3511},
}
@article {pmid41720282,
year = {2026},
author = {Fudim, M and Novak, P and Taub, PR and Chung, T and Zimmerman, KO and Moy, OV and Fissler, HZ and Wen, J and Freeman, NLB and O'Brien, S and Marti, H and Cook, D and Low, P and Kim, DY and Rosenberg, Y and Granger, CB and Shibao, CA},
title = {Design and rationale of RECOVER-AUTONOMIC: A randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome.},
journal = {American heart journal},
volume = {296},
number = {},
pages = {107384},
doi = {10.1016/j.ahj.2026.107384},
pmid = {41720282},
issn = {1097-6744},
abstract = {BACKGROUND: Post‑acute sequelae of SARS‑CoV‑2 infection (Long COVID) affect a substantial proportion of individuals, and among the many reported symptom clusters, autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), represents an important subset. The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative developed by the National Institutes of Health included a platform trial (RECOVER-AUTONOMIC) designed to assess the safety, tolerability, and efficacy of 3 interventions-(1) coordinated nonpharmacologic care, (2) pharmacotherapy with intravenous immunoglobulin (IVIG), and (3) pharmacotherapy with ivabradine-in treating POTS in adults with Long COVID.<br><br>METHODS: RECOVER-AUTONOMIC is a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. Participants are randomized to IVIG or ivabradine with matching placebo, and (in a factorial design) to either coordinated nonpharmacologic care or usual care. The primary endpoint is the change in orthostatic intolerance symptoms measured by the Orthostatic Hypotension Questionnaire/Orthostatic Intolerance Questionnaire from baseline to the end of intervention. Secondary endpoints include quality of life, functional performance, symptom burden, and safety. Exploratory endpoints include autonomic function testing, wearable sensor data, and longitudinal biomarker profiling.<br><br>DISCUSSION: RECOVER-AUTONOMIC seeks to determine the benefits and risks of IVIG and of ivabradine, as well as of coordinated nonpharmacologic care, for the treatment of POTS in Long COVID. Results from this trial will offer the largest source of evidence to help guide the medical care of this population.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov-Platform: NCT06305780; Appendix A (intravenous immunoglobulin): NCT06305793; Appendix B (ivabradine): NCT06305806. Protocol available at https://trials.recovercovid.org/autonomic.},
}
@article {pmid41720041,
year = {2026},
author = {Nakase, T and Takano, Y and Nomura, S and Baek, HW and Takayama, S and Ono, R and Abe, M and Ishii, T and Tatewaki, Y and Taki, Y},
title = {Association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers.},
journal = {Journal of the neurological sciences},
volume = {483},
number = {},
pages = {125808},
doi = {10.1016/j.jns.2026.125808},
pmid = {41720041},
issn = {1878-5883},
abstract = {BACKGROUND: Some patients recovered from COVID-19 may experience cognitive and psychological symptoms, such as "brain fog" or neuropsychological long COVID, and its mechanism is unclear.<br><br>OBJECTIVE: This study aimed to investigate the mechanism of brain damage in neuropsychological long COVID using imaging and blood biomarkers.<br><br>METHODS: Patients who met the criteria on the "brain fog" screening questionnaire and provided informed consent were enrolled in this study (n&#xa0;=&#xa0;33; mean age 38.5&#xa0;years). All participants were examined using magnetic resonance imaging, single-photon emission computed tomography (assessment of regional cerebral blood flow [rCBF]), and blood biomarkers. Neuropsychological tests (Montreal Cognitive Assessment-Japanese version [MoCA-J], Trail Making Test [TMT], Frontal Assessment Battery, Digital Symbol Coding [DSC] test, State-Trait Anxiety Inventory [STAI], and Self-Rating Depression Scale [SDS]) were performed simultaneously.<br><br>RESULTS: Significant correlations were observed between the MoCA-J score and decreased rCBF in the left occipital lobe and increased rCBF in the right occipital lobe (p&#xa0;<&#xa0;0.05), between the STAI score and decreased rCBF in the right parietal lobe (p&#xa0;<&#xa0;0.05), and between the SDS score and decreased rCBF in the right parietal lobe (p&#xa0;<&#xa0;0.05). The MoCA-J and DSC scores were correlated with plasma levels of neurofilament light chain (p&#xa0;<&#xa0;0 0.05). The TMT time correlated with plasma glial fibrillary acidic protein levels (p&#xa0;<&#xa0;0.01).<br><br>CONCLUSION: This study was a cross-sectional and could not distinguish pathological abnormalities. However, as correlations of neuropsychological long COVID with specific brain regions and plasma biomarkers have been elucidated, conducting a case-control analysis may be worthwhile.},
}
@article {pmid41718988,
year = {2026},
author = {Wang, Y and Gandy, S},
title = {Golgi Fragmentation as a Potential Link Between SARS-CoV-2 Infection and Alzheimer's Disease: Mechanisms and Implications for Neurodegeneration in Long COVID.},
journal = {Sub-cellular biochemistry},
volume = {111},
number = {},
pages = {463-482},
pmid = {41718988},
issn = {0306-0225},
mesh = {Humans ; *Alzheimer Disease/pathology/metabolism/virology ; *COVID-19/pathology/complications/metabolism/virology ; *Golgi Apparatus/pathology/metabolism/virology ; *SARS-CoV-2/metabolism ; Animals ; },
abstract = {The COVID-19 pandemic has impacted millions of people worldwide, and recent studies have shown that SARS-CoV-2 infection can lead to an Alzheimer's-like neuropathological and biomarker phenotype, as well as clinical symptoms of "brain fog". This raises an intriguing question: "How and where might the molecular pathways underlying SARS-CoV-2 infection and Alzheimer's disease (AD) converge?" One common feature of both SARS-CoV-2 infection and AD is the alteration of the endomembrane system, particularly the fragmentation of the Golgi apparatus. In this review article, we summarize the existing literature on SARS-CoV-2 infection biology and speculate about the potential mechanisms linking Golgi defects, SARS-CoV-2 infection, and neurodegeneration.},
}
@article {pmid41718450,
year = {2026},
author = {Ribatti, RM and Lanciano, T and Curci, A},
title = {Detecting Malingered COVID-19 Symptoms Using the Verifiability Approach.},
journal = {Brain and behavior},
volume = {16},
number = {2},
pages = {e71278},
pmid = {41718450},
issn = {2162-3279},
mesh = {Humans ; *COVID-19/diagnosis/psychology ; *Malingering/diagnosis/psychology ; Female ; Male ; Adult ; Middle Aged ; Deception ; Young Adult ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: The COVID-19 pandemic has heightened concerns about malingering, particularly given its recognition as an occupational disease in several regions. This study evaluated the applicability of the Verifiability Approach (VA), a credibility assessment tool based on the principle that liars provide fewer verifiable details than truth tellers, to distinguish between honest reporters and malingerers of COVID-19 infection.<br><br>METHODS: A total of 410 participants (51.5% female) completed an online survey via Google Forms. Participants who reported previous COVID-19 infection (n&#xa0;=&#xa0;205) were assigned to either an informed honest (n&#xa0;=&#xa0;104) or not-informed honest (n&#xa0;=&#xa0;101) group, while those without prior infection (n&#xa0;=&#xa0;205) were assigned to informed malingerers (n&#xa0;=&#xa0;105) or not-informed malingerers (n&#xa0;=&#xa0;100) conditions. Participants in the informed condition were briefed about the VA before writing their reports.<br><br>RESULTS: Informed honest participants provided significantly more verifiable details than both uninformed honest participants and malingerers. The number of verifiable details and the ratio of verifiable details to total details were strongly associated with honesty when participants were informed about the VA, indicating that the information Protocol enhanced diagnostic accuracy. Perceived success was higher among honest participants, particularly those informed about the VA. No significant effects emerged for reported long COVID or fabricated symptoms, likely due to limited variability and low symptom familiarity.<br><br>CONCLUSION: The findings support the VA's validity in distinguishing genuine from feigned symptom reports in health-related contexts. However, the fully online design, lack of factual verification, and potential for misreporting represent key limitations. Future studies should replicate these results in face-to-face or ecologically valid settings and extend the VA framework to the study of symptom dissimulation.},
}
@article {pmid41717886,
year = {2026},
author = {Cucunawangsih, C and Ansori, ANM and Vatvani, AD and Hariyanto, TI},
title = {Impact of nirmatrelvir/ritonavir on the risk of long COVID in outpatients: a systematic review and meta-analysis.},
journal = {Expert review of anti-infective therapy},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/14787210.2026.2636175},
pmid = {41717886},
issn = {1744-8336},
abstract = {BACKGROUND: This study systematically synthesized existing evidence to evaluate whether outpatient treatment with nirmatrelvir/ritonavir during the acute phase reduces the incidence of long COVID.<br><br>METHODS: We conducted a systematic search of Europe PMC, Medline, Scopus, and the Cochrane Library from inception to 15 September 2025. Eligible studies compared COVID-19 outpatients prescribed nirmatrelvir/ritonavir during the acute phase with those who did not receive the drug. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model.<br><br>RESULTS: Nineteen studies met inclusion criteria. Overall, nirmatrelvir/ritonavir use during acute infection was associated with a significant reduction in the likelihood of developing post-COVID-19 condition (OR 0.85; 95% CI: 0.80-0.91; p&#x2009;<&#x2009;0.00001; I[2]&#x2009;=&#x2009;99%). Protective effects were consistently observed across multiple clinical domains, including cardiovascular (arrhythmia, ischemic disease, heart failure), pulmonary (dyspnea, COPD), thromboembolic (DVT, PE), neurological (stroke, cognitive impairment, headache), psychiatric (depression), gastrointestinal, metabolic (new-onset diabetes), renal (AKI), and general symptoms (malaise and fatigue). Conversely, no significant differences were noted for cough, asthma, dysautonomia, anxiety, PTSD, sleep disturbances, musculoskeletal pain, or olfactory/gustatory dysfunction.<br><br>CONCLUSIONS: Early outpatient treatment with nirmatrelvir/ritonavir may mitigate the risk of developing several domains of long COVID, though its benefits are not uniform across all symptom categories.},
}
@article {pmid41713328,
year = {2026},
author = {Barboza, APB and Luna-Muschi, A and Faffe, D and Borges, IC and Côrtes, MF and Galliez, R and Mendes, ET and Leal, FE and Manuli, E and Ghilardi, F and Scheid, HT and Lourenço, ABM and Ozatha, M and Sampaio, V and da Costa Ferreira Junior, O and Tanuri, A and Sabino, E and Castiñeiras, TM and Costa, SF},
title = {Protective effect of a second booster dose against long COVID among individuals infected with SARS-CoV-2 in southeastern Brazil.},
journal = {Vaccine},
volume = {77},
number = {},
pages = {128354},
doi = {10.1016/j.vaccine.2026.128354},
pmid = {41713328},
issn = {1873-2518},
abstract = {BACKGROUND: Long COVID is a complex condition with diverse symptoms, lacking specific diagnostic or therapeutic tools. Although vaccination reduces the risk of severe COVID-19, its role in preventing long COVID, particularly through booster doses, remains limited. This study assessed the impact of first and second booster doses and identified long COVID risk factors.<br><br>METHODS: We conducted a multicenter observational study with a cross-sectional analysis of participants previously infected with SARS-CoV-2 during the pre-Omicron and Omicron epidemiological periods. Both periods included mixed populations of healthcare workers (HCWs) and non-HCWs, with HCWs representing 86% of all participants. The study included five medical centers in S&#xe3;o Paulo and Rio de Janeiro. Clinical data and long COVID symptoms were collected through a single standardized electronic questionnaire sent to all eligible participants. Predictors of long COVID were evaluated using multivariable logistic regression. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.<br><br>RESULTS: A total of 2033 participants were included, and 67% (1370) reported long COVID symptoms. Independent risk factors included female sex (OR 2.25, 95% CI 1.81-2.79, p&#xa0;<&#xa0;0.001), the presence of one, two, or three or more comorbidities (OR 1.74, 95% CI 1.36-2.23, p&#xa0;<&#xa0;0.001; OR 2.14, 95% CI 1.43-3.20, p&#xa0;<&#xa0;0.001; and OR 3.10, CI 1.55-6.19, p&#xa0;=&#xa0;0.001, respectively); the occurrence of one or more reinfections (OR 2.35, 95% CI 1.84-3.01, p&#xa0;<&#xa0;0.001; and OR 4.22, 95% CI 2.043-7.91, p&#xa0;<&#xa0;0.001, respectively), and a severe acute illness (OR: 1.91; 95%CI 1.09-3.35; p&#xa0;=&#xa0;0.02). Vaccination was protective, with the strongest effect observed among those receiving two booster doses (OR: 0.18; 95% CI 0.07-0.46; p&#xa0;<&#xa0;0.001). In the Omicron period sub-analysis, only the second booster dose was associated with reduced risk compared with a complete primary series (OR 0.50, CI 0.34-0.74, p&#xa0;<&#xa0;0.001), whereas one booster dose showed no significant effect.<br><br>CONCLUSION: COVID-19 vaccination, especially two booster doses, reduced long COVID risk. Female sex, comorbidities, reinfections, and severe acute illness were independent risk factors for developing long-lasting symptoms.},
}
@article {pmid41712280,
year = {2026},
author = {Izquierdo-Pujol, J and Pedreño-Lopez, N and Pidkova, T and Nevot, M and Urrea, V and Laguía, F and Muñoz-López, F and Dalmau, J and Gonzalez-Aumatell, A and Carreras-Abad, C and Méndez, M and Rodrigo, C and Massanella, M and Blanco, J and Carrillo, J and Trinité, B and Martinez-Picado, J and Morón-López, S},
title = {Pediatric long COVID is characterized by myeloid CCR6 suppression and immune dysregulation.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.201111},
pmid = {41712280},
issn = {2379-3708},
abstract = {The biological mechanisms underlying long COVID in the pediatric population are poorly understood. Our study aimed to characterize the immune pathophysiology of long COVID in children and young people (CYP). We analyzed major immune cell compartments in PBMCs, as well as specific SARS-CoV-2 antibody response in CYP with (n=99) and without (n=18) long COVID at three months following acute infection. Our findings indicate that pediatric long COVID is associated with a dysregulated immune response characterized by altered innate immunity and overactivated T-, B- and NK-cell responses. Furthermore, CYP with long COVID had an impaired humoral response to SARS-CoV-2 marked by a dysregulated B-cell compartment and lower levels of anti-RBD IgG and IgA. This correlated with reduced neutralizing capacity against SARS-CoV-2. Random forest analysis identified CCR6 expression on myeloid cells as the most relevant biomarker that distinguishes long COVID from control individuals with 79% accuracy.},
}
@article {pmid41712028,
year = {2026},
author = {Chakraborty, C and Bhattacharya, M and Chatterjee, S and Lee, SS},
title = {Long COVID-associated neurological symptoms and brain fog: Understanding the mechanism of neuroinflammation, BBB disruption, diagnostics, and therapeutics.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {401},
pmid = {41712028},
issn = {1573-4978},
mesh = {Humans ; *Blood-Brain Barrier/pathology/metabolism/virology ; *COVID-19/complications/diagnosis/therapy ; *Neuroinflammatory Diseases/diagnosis/therapy/virology ; SARS-CoV-2 ; Animals ; Brain/pathology/virology ; *Nervous System Diseases/diagnosis/therapy/etiology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID affects at least 10% of those with severe disease, and many experience neurological symptoms and brain fog. More than 200 symptoms are reported, yet a detailed understanding remains limited. This article summarizes current knowledge of neurological symptoms, brain fog, molecular mechanisms, neuroinflammation, blood-brain barrier disruption, diagnostics, and available therapeutics. Our review highlights the lack of diagnostics and treatments for these patients. We catalog the ongoing clinical trials, identify the urgent need for further therapeutics, and stress that advances in understanding pathophysiology will drive new treatments. We urge prioritizing animal model studies and improving diagnostics to accelerate the discovery and delivery of effective treatments for long COVID neurological symptoms.},
}
@article {pmid41709214,
year = {2026},
author = {Ryu, S and Patel, A and Chyu, C and Buszkiewicz, JH and Ahmed, S and Fleischer, NL},
title = {Prospective associations between Long COVID and mental health: evidence from a population-based study with a nearly three-year follow-up.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-26659-z},
pmid = {41709214},
issn = {1471-2458},
support = {6 NU50CK000510-02-04/CC/CDC HHS/United States ; },
abstract = {BACKGROUND: Many adults with Long COVID experience adverse mental health outcomes, but the long-term persistence of these associations remains unclear. We examined the prospective associations of Long COVID with depressive and anxiety symptoms three years after initial infection.<br><br>METHODS: We used a population-based cohort of Michigan adults with PCR-confirmed COVID-19, excluding respondents with baseline symptoms (resulting analytic samples: n&#x2009;=&#x2009;2,431 for depressive symptoms; n&#x2009;=&#x2009;2,301 for anxiety symptoms). Long COVID was defined as symptoms lasting&#x2009;&#x2265;&#x2009;90&#xa0;days after initial infection, assessed at baseline (median 4.4&#xa0;months post-infection). Depressive and anxiety symptoms were evaluated 1.5&#xa0;years (follow-up 1) and 3&#xa0;years (follow-up 2) after infection. We used modified Poisson regression models to estimate risk ratios (RR) for each outcome and multinomial logistic regression models to examine Long COVID and mental health outcomes measured across two follow-up periods.<br><br>RESULTS: Long COVID was associated with higher risks of depressive symptoms (aRR:1.86, 95% CI:1.34-2.57) and anxiety symptoms (aRR:1.60, 95% CI:1.18-2.16) after 3&#xa0;years of follow-up. Adults with Long COVID, compared to adults without Long COVID, had a 2.64 times higher risk of depressive symptoms at follow-up 2 (95% CI:1.60-4.35) relative to no depressive symptoms at either follow-up and a 2.48 times higher risk of anxiety symptoms at both follow-ups (95% CI:1.38-4.47) relative to no anxiety symptoms at either follow-up.<br><br>CONCLUSION: Our findings that Long COVID is associated with higher depressive and anxiety symptoms after 3&#xa0;years of follow-up highlight the need to monitor the mental health of adults with Long COVID.},
}
@article {pmid41708407,
year = {2026},
author = {Maji, C and Kokiwar, PR and Biradar, A and Jauhari, R},
title = {Comment on "Prevalence and trajectories of post-COVID-19 neuromuscular conditions: A systematic-review and meta-analysis".},
journal = {Journal of the neurological sciences},
volume = {482},
number = {},
pages = {125811},
doi = {10.1016/j.jns.2026.125811},
pmid = {41708407},
issn = {1878-5883},
}
@article {pmid41707177,
year = {2026},
author = {Zhang, TM and Sharp, SP and Scott, JD and Taren, D and Samaniego, JC and Unger, ER and Bertolli, J and Lin, JS and Ramers, CB and Godino, JG},
title = {Correction: Characterization of Post-Viral Infection Behaviors Among Patients With Long COVID: Prospective, Observational, Longitudinal Cohort Analyses of Fitbit Data and Patient-Reported Outcomes.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e92848},
doi = {10.2196/92848},
pmid = {41707177},
issn = {2561-326X},
abstract = {[This corrects the article DOI: 10.2196/77644.].},
}
@article {pmid41705124,
year = {2025},
author = {Wirth, KJ and Steinacker, JM},
title = {The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1693589},
pmid = {41705124},
issn = {1664-042X},
abstract = {Patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are bedridden and suffer from hypersensitivities to light and noise, severe orthostatic intolerance reducing cerebral blood flow, and skeletal muscle symptoms, including loss of force, fatigue, pain, fasciculations, and cramps. Because neurological investigations exclude neuronal causes of myasthenia, we hypothesize a muscular pathomechanism. In previous articles, we considered insufficient activity of the Na[+]/K[+]-ATPase to be the main cause of mitochondrial damage via high intracellular sodium that reverses the transport mode of the sodium-calcium-exchanger to import calcium, causing calcium overload. Low Na[+]/K[+]-ATPase activity also causes sarcolemmal depolarization, leading to less effective action potential propagation and loss of force. Depolarization brings the membrane potential closer to the threshold potential, causing hyperexcitability that explains fasciculations and cramps. These increase sodium influx during excitation to further increase the workload of Na[+]/K[+]-ATPase. Thereby, depolarization causes further depolarization. Higher intracellular sodium favors calcium overload and mitochondrial damage, which lowers the energy supply of Na[+]/K[+]-ATPase and increases the reactive oxygen species, further inhibiting Na[+]/K[+]-ATPase. The muscle is in a state of depolarization even at rest. Depolarization and mitochondrial damage reinforce each other. Thus, dysfunction of Na[+]/K[+]-ATPase as a single mechanism can explain the different skeletal muscle symptoms of severely ill ME/CFS patients, comprising loss of force, fatigue, and fasciculations.},
}
@article {pmid41704685,
year = {2026},
author = {Andus, I and Büttner, J and Bochow-Fitzner, B and Tacke, F and Jochum, C},
title = {Intestinal permeability correlated with chronic fatigue in a patient with long COVID-A case report and overview of the literature.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1725242},
pmid = {41704685},
issn = {2296-858X},
abstract = {BACKGROUND: Long COVID is a complex condition characterized by persistent symptoms such as chronic fatigue, cognitive impairment, and autonomic dysfunction. Emerging evidence suggests that the gut may play a role in the pathophysiology of long COVID, potentially contributing to systemic inflammation and symptom severity. Prior studies indicate intestinal permeability (IP) alteration in patients with long COVID. To date, there have been no reports on the assessment of intestinal permeability via carbohydrate absorption in individuals with long COVID.<br><br>CASE PRESENTATION: We present a 60-year-old female with long COVID who exhibited chronic fatigue and autonomic dysfunction for more than 3 years following SARS-CoV-2 infection. IP was assessed at five time points using a carbohydrate absorption test. Results revealed significantly elevated lactulose/mannitol (L/M) ratios during episodes of symptom exacerbation, including a second SARS-CoV-2 infection. Notably, clinically observed improvement in fatigue correlated with a reduction in IP. A probiotic regimen with Bacillus coagulans and Bacillus subtilis, combined with a second intervention using medicinal clay, led to further clinical improvement.<br><br>CONCLUSIONS: This case report demonstrates a correlation between intestinal permeability alterations and long COVID symptom severity. Notably, to our knowledge, this is the first report assessing intestinal permeability in a long COVID patient using a carbohydrate absorption-based permeability test. It reinforces the emerging link between gut barrier integrity and long COVID pathophysiology and emphasizes the need for further studies to assess IP as a potential disease marker. Furthermore, the observed improvement with probiotic therapy highlights the need for further research into microbiome-targeted interventions for long COVID management. Larger studies are required to explore the mechanistic link between gut permeability and long COVID pathophysiology.},
}
@article {pmid41703367,
year = {2026},
author = {Nanthakumar, P and Law, JX and Ng, SF},
title = {Fibroblast-derived small extracellular vesicles loaded with tacrolimus enhances dermal delivery and alleviates cytokine-overdriven skin inflammation.},
journal = {Drug delivery and translational research},
volume = {},
number = {},
pages = {},
pmid = {41703367},
issn = {2190-3948},
support = {FRGS/1/2022/SKK16/UKM/02/5//Kementerian Pendidikan Malaysia/ ; },
abstract = {Long COVID has been increasingly linked to chronic inflammatory skin conditions driven by cytokine overproduction. Topical tacrolimus, a calcineurin inhibitor, is commonly used to manage such conditions due to its immunosuppressive properties. However, due to poor dermal penetration, tacrolimus oftens produce to suboptimal efficacy and adverse effects such as local irritation and burning sensation. Effective management of chronic inflammatory skin conditions linked to long COVID necessitates targeted, controlled drug delivery into deeper skin layers to modulate excessive cytokine production and attenuate localized inflammation. This study explores fibroblast-derived small extracellular vesicles (sEVs) as a new controlled delivery vehicle for tacrolimus. The sEVs were isolated using sucrose-cushioned density ultracentrifugation and characterized by TEM, NTA, Dot blot, and MicroBCA assay, confirming their successful isolation and purity. Tacrolimus was encapsulated into sEVs via sonication, with successful drug loading confirmed by morphological and physicochemical characterization. The resulting Tac-sEVs exhibited an encapsulation efficiency of 79.19% ± 0.01. Franz diffusion studies revealed a rapid initial release within the first 10 h, followed by sustained higher release over time. Tape-stripping demonstrated significantly deeper dermal penetration of tacrolimus loaded sEVs (Tac-sEVs) compared with commercial tacrolimus ointment and free drug. Both tacrolimus and Tac-sEVs downregulated IFN-γ, GCS-F, IL-2, and IL-4 expression, indicating potent suppression of SARS-CoV-2 spike glycoprotein-induced cytokine overproduction. PKH-26 fluorescence labelling confirmed efficient cellular uptake, while cytotoxicity assays (Alamar Blue, CCK-8) showed high cell viability for both formulations. In summary, these results position Tac-sEVs as a safe and promising therapeutic platform for cytokine-driven inflammatory skin diseases associated with long COVID, meriting further clinical investigation.},
}
@article {pmid41701690,
year = {2026},
author = {Martínez-Borba, V and Rodríguez-Márquez, AE and Garcés-Arilla, S and Peris-Baquero, &#xd3; and Navarro-Haro, MV and Del Corral-Beamonte, E and Osma, J},
title = {Effectiveness and acceptability of the unified protocol for the transdiagnostic treatment of emotional disorders in people with long COVID-19: Study protocol for a randomized controlled trial.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0342908},
pmid = {41701690},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/psychology/complications ; Adult ; Female ; SARS-CoV-2/isolation &amp; purification ; Male ; Hydrocortisone/analysis ; Randomized Controlled Trials as Topic ; Middle Aged ; Treatment Outcome ; Depression/therapy ; Emotions ; Neuropsychological Tests ; },
abstract = {BACKGROUND: Long COVID-19 is a medical condition associated with persistent physical, cognitive, and emotional symptoms. Despite its significant impact, there are still few psychological interventions-especially with transdiagnostic approaches- that have been rigorously tested in this population. The aim of the present protocol is to describe a randomized controlled trial to examine the effectiveness and acceptability of the online, group-delivered Unified Protocol (UP) for improving emotional, and cognitive outcomes in adults with long COVID-19. We expect greater improvements in emotional and cognitive outcomes for the UP group compared to controls. Additionally, exploratory analyses will assess changes in neurocognitive performance and hair cortisol/cortisone levels as potential correlates of treatment response.<br><br>METHODS: 90 individuals diagnosed with long COVID-19 will be randomized to an experimental group or a waiting-list control group (1:1 ratio). Participants in the experimental group will receive the UP across 12 online group sessions. Longitudinal assessments (pre-treatment, post-treatment and 3, 6 and 12 months follow-ups) will include psychological (e.g., anxiety and depressive symptoms) and cognitive outcomes (e.g., memory failures). Participants in the experimental group will also complete neuropsychological tests and will provide hair samples for the assessment of cortisol/cortisone levels.<br><br>DATA ANALYSES: Baseline characteristics will be described using descriptive statistics, and linear mixed-effects models will evaluate the effects of time, group, and their interaction on psychological and cognitive outcomes. Neuropsychological performance and hair cortisol levels will be analyzed over time in the experimental group. Associations between cortisol and psychological or cognitive measures will be explored through correlational analyses.<br><br>CONCLUSIONS: We expect positive outcomes after the intervention in acceptability and in emotional symptoms and cognitive complaints in individuals living with long COVID-19, the maintenance of the benefits in all follow-ups, and statistically significant changes in favor of the UP condition in comparison with the waiting-list control group. If effective, the UP could provide an accessible and evidence-based psychological treatment for this population, improving the quality of healthcare to individuals with long COVID-19.<br><br>TRIAL REGISTRATION: clinicatrials.gov (registration identifier: NCT06928480; May 22, 2025).},
}
@article {pmid41700293,
year = {2026},
author = {Meyahnwi, D and Issaka, Y and Okorigba, EM and Agberien, VO and Joshi, S and Port, Z},
title = {Short- and Long-Term Prognosis of COVID-19-Associated Versus Non-COVID-19 Takotsubo Cardiomyopathy: A Propensity-Matched Nationwide Study.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101631},
pmid = {41700293},
issn = {2168-8184},
abstract = {BACKGROUND: Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy with transient left ventricular dysfunction, often triggered by acute illness. Coronavirus disease 2019 (COVID-19) has been implicated as a precipitant, but comparative outcome data for COVID-19-related versus non-COVID-19 TCM remain largely limited to the early pandemic, when few effective treatments existed.<br><br>METHODS: We conducted a retrospective cohort study using the TriNetX database, identifying US adults hospitalized between March 2020 and March 2025 with TCM and created two cohorts: patients with TCM and laboratory-confirmed COVID-19 and patients with TCM without COVID-19, both diagnosed within 14 days of admission. The primary outcome was 30-day all-cause mortality, with secondary 30-day outcomes and one-year mortality also assessed. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated.<br><br>RESULTS: Of 16,649 patients (6,367 COVID-19 TCM and 10,282 non-COVID-19 TCM), 5,955 per group remained after propensity score matching. Baseline demographics and comorbidities were well balanced (mean age 66.8 years; 76.8% female). Thirty-day mortality did not differ significantly between COVID-19 and non-COVID-19 TCM (12.0% vs. 11.1%; HR 1.07, 95% CI 0.97-1.19). However, COVID-19 TCM was associated with higher risks of heart failure with reduced ejection fraction (HFrEF) (HR 1.18, 95% CI 1.10-1.26), cardiogenic shock (HR 1.25, 95% CI 1.08-1.46), and ventricular arrhythmias (HR 1.37, 95% CI 1.14-1.64). One-year mortality was significantly higher in the COVID-19 cohort (22.0% vs. 18.3%; HR 1.19, 95% CI 1.10-1.29).<br><br>CONCLUSION: COVID-19-associated TCM is not linked to excess short-term mortality but carries higher risks of acute complications and significantly worse one-year survival, highlighting the persistent effects of COVID-19 after an acute infection.},
}
@article {pmid41699766,
year = {2026},
author = {Das, V},
title = {Trends in Financial Hardship by COVID-19 Infection History, Long COVID Status, and Day-to-Day Activity Limitations: A National Study of US Adults.},
journal = {Family &amp; community health},
volume = {49},
number = {2},
pages = {122-130},
pmid = {41699766},
issn = {1550-5057},
mesh = {Humans ; *COVID-19/economics/epidemiology ; United States/epidemiology ; Male ; Female ; Adult ; Middle Aged ; *Financial Stress/epidemiology/economics ; SARS-CoV-2 ; *Health Status ; Aged ; *Activities of Daily Living ; Logistic Models ; Young Adult ; Adolescent ; },
abstract = {BACKGROUND AND OBJECTIVE: This study investigated whether the association between COVID-19 health status and financial hardship changed over time.<br><br>METHODS: Weighted logistic regression analyses were conducted using data from 1&#xa0;367&#xa0;829 adults surveyed in the US Census Bureau's Household Pulse Survey (October 2022-September 2024) to estimate the average marginal effects of COVID-19 health status on financial hardship.<br><br>RESULTS: Adjusted logistic regression estimates showed that financial hardship was, on average, 27 percentage points higher for those reporting long COVID with severe activity limitations and 9 points higher for those with mild limitations, compared to never-infected adults. The differences in financial hardship across groups with different COVID-19 health status remained largely stable throughout the 2-year study period.<br><br>CONCLUSIONS: The persistent link between activity-limiting long COVID and financial hardship underscores the need for integrated policy responses.},
}
@article {pmid41699511,
year = {2026},
author = {Engl, K and Feddern, S and Grüne, B and Haberstock, L and Kossow, A and Nießen, J and Rost, S and Wiesmüller, GA and Schmidt, N and Joisten, C},
title = {Prevalence, symptoms, and associated factors of long COVID: a retrospective cohort study based on data from two major German health authorities.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-12785-x},
pmid = {41699511},
issn = {1471-2334},
}
@article {pmid41699192,
year = {2026},
author = {Whong, Z and Malik, A and Calder, AN and Armstrong, MF and Schuman, TA},
title = {COVID-19 Infection Increases the Risk of Subsequent Diagnosis of Chronic Rhinosinusitis.},
journal = {The Laryngoscope},
volume = {},
number = {},
pages = {},
doi = {10.1002/lary.70444},
pmid = {41699192},
issn = {1531-4995},
abstract = {OBJECTIVES: To analyze the impact of COVID-19 infection on the diagnosis of chronic rhinosinusitis (CRS).<br><br>METHODS: TriNetX, a large international database of anonymized health records, was queried for adults with either positive or negative SARS-CoV-2 polymerase chain reaction (PCR) tests between March 1, 2020 and December 31, 2024. Patients with cancer or immunodeficiency before the COVID-19 diagnosis were excluded. Propensity score matching was used to create comparable exposure and control groups. Relative risk ratios and Cox proportional hazards regression analysis of CRS diagnosis were calculated 3 months after PCR testing. Sub-analyses were completed to investigate the effects of prior COVID-19 infection on subsequent CRS development stratified by prior vaccination status and by variant-dominant time periods (pre-Delta, Delta, and Omicron).<br><br>RESULTS: Propensity score-matched COVID-19+ and COVID-19- cohorts each consisted of 2,135,446 patients. Rate of diagnosis of CRS increased following a positive COVID-19 PCR test (RR&#x2009;=&#x2009;2.13, 95% CI [2.10-2.16]) and varied across variant-dominant periods, with risk ratios of 1.44 (95% CI [1.41-1.47]) during pre-Delta, 1.20 (95% CI [1.15-1.25]) during Delta, and 2.10 (95% CI [2.07-2.13]) during Omicron. Prior COVID-19 vaccination did not modify the risk of CRS among patients with a positive COVID-19 PCR (RR&#x2009;=&#x2009;0.98, 95% CI [0.92-1.05]).<br><br>CONCLUSIONS: COVID-19 infection was found to increase the risk of subsequent diagnosis of CRS. Further studies are needed to better understand the relationship between COVID-19 and the development of sinonasal inflammatory pathology.},
}
@article {pmid41697443,
year = {2026},
author = {Camara, B and Buonsenso, D},
title = {Biomarkers of long COVID in children and young adults: a scoping review.},
journal = {European journal of pediatrics},
volume = {185},
number = {3},
pages = {132},
pmid = {41697443},
issn = {1432-1076},
mesh = {Humans ; *COVID-19/complications/diagnosis ; Child ; *Biomarkers/blood ; Adolescent ; Young Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {UNLABELLED: Following the SARS-CoV-2 pandemic, a significant percentage of people are now experiencing long-term symptoms, despite a continuing lack of concrete documentation of physiological and risk profiles that hinders diagnosis and treatment, particularly in pediatric contexts. This review aims to highlight the existing evidence for measurable physiological markers for post-acute sequelae of SARS-CoV-2 infection (long COVID) in children, adolescents, and young adults. Titles providing data related to measurable biomarkers distinguishing young long COVID patients from controls were compiled and analyzed. Results were displayed in table and diagram form for optimal qualitative evaluation of the relationship between markers and symptomatology within the context of each organ system. Only human studies published in English, Italian, Portuguese, German, and Spanish between the 5th of February 2025 and the 31st of December 2025 were considered, and no other time constraints were applied. Following search and criteria evaluation, nine studies were included, totaling 41 occurrences identified in diseased patients with statistically significant variation from healthy controls. Markers suggest the presence of organic manifestations based on published literature, although more data and future studies will be necessary to establish clear connections.<br><br>CONCLUSION: The data compiled for this review adds to the body of evidence indicating a physiological manifestation of long COVID and its consequences. Further investigation into potential risk factors, pre- and post-pubescent manifestations, and specific inflammatory and immune pathways will be necessary for a more concrete understanding of long COVID and its effects on children, adolescents, and young adults.<br><br>WHAT IS KNOWN: &#x2022; Long COVID is estimated to affect a significant population of patients, despite the lack of concrete physiological diagnostic and prognostic measures. &#x2022; Pediatric incidence of the disease is still largely debated, and published data are scarce.<br><br>WHAT IS NEW: &#x2022; A total of 41 biomarker occurrences were identified by selected studies, which were consistent with expected physiology behind reported symptoms. &#x2022; The body of data discussed suggests the presence of physiological phenomena behind the long-term symptoms experienced by pediatric long- COVID patients.},
}
@article {pmid41696720,
year = {2026},
author = {Ohira, M and Osada, T and Kimura, H and Sano, T and Takao, M},
title = {Clinical Characteristics of Patients Initially Suspected of Long COVID: A Case Series From a Specialized Outpatient Clinic.},
journal = {Journal of general and family medicine},
volume = {27},
number = {1},
pages = {e70081},
pmid = {41696720},
issn = {2189-7948},
abstract = {BACKGROUND: Sequelae of the acute phase of coronavirus disease 2019 (COVID-19), termed long COVID, are characterized by a variety of symptoms, including neurological manifestations. Diagnosing long COVID requires excluding alternative conditions that could explain the symptoms. The role of primary care physicians is considered essential in managing long COVID, particularly during the initial screening phase.<br><br>METHODS: This observational, retrospective, single-center study was conducted at an outpatient clinic from 1 June 2021 to 31 December 2024. We confirmed final diagnoses for patients suspected of having long COVID and included those ultimately diagnosed with other conditions. Clinical data-including symptoms, demographic characteristics, results of clinical examinations, and final diagnoses-were collected.<br><br>RESULTS: In total, 44 patients were diagnosed with alternative conditions. Of these, 30 were classified as having post-acute sequelae of SARS-CoV-2 mimic, and 14 patients (2.2% of those who believed they had long COVID and visited our clinic) were diagnosed with other diseases. The median age at the time of their clinic visit was 48&#x2009;years (range, 42.5-61.5). Diagnoses included collagen diseases (5 patients, 35.7%) and central nervous system disorders (5 patients, 35.7%), among others. Weakness was the most common symptom. In contrast to long COVID, fatigue was less frequently reported in this group.<br><br>CONCLUSIONS: We identified a variety of alternative diagnoses among patients suspected of having long COVID. We recommend that primary care physicians exercise caution when diagnosing long COVID, particularly in patients who do not report fatigue.},
}
@article {pmid41695601,
year = {2026},
author = {O'Hanlon, J and Sullivan, K and Muehling, LM and Canderan, G and Sun, J and Woodfolk, JA and Wilson, JM and Luke, RA},
title = {A Probabilistic Modeling Analysis of the Longitudinal Immune Response to Infection and Vaccination Across Demographic Groups and Pulmonary Symptoms.},
journal = {Spora : a journal of biomathematics},
volume = {12},
number = {},
pages = {59-75},
pmid = {41695601},
issn = {2473-5493},
support = {R21 AI160334/AI/NIAID NIH HHS/United States ; R56 AI178669/AI/NIAID NIH HHS/United States ; },
abstract = {Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine models suggest that those with pulmonary symptoms post-acute infection have elevated responses over time. Further, we find that the cytokine response increases and then decays more rapidly than the antibody response. These results are consistent with clinical observations.},
}
@article {pmid41695180,
year = {2026},
author = {Popović, B and Lesac Brizić, A and Ljubotina, A and Zavidić, T and Tudor Špalj, V and Marković Štimac, R and Fišić Jurković, M and Bašić Marković, N and Diminić Lisica, I and Vučak, J and Radošević Quadranti, N},
title = {Long-term health effects of COVID-19 among patients in Croatian primary care settings.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1740432},
pmid = {41695180},
issn = {2296-858X},
abstract = {INTRODUCTION: The COVID-19 pandemic has left lasting effects that extend beyond the acute phase of infection, with increasing evidence of long-term health consequences. This study aimed to assess the prevalence of post-COVID symptoms and conditions and to identify associated risk factors, including pre-existing chronic diseases, COVID-19 vaccination status, and severity of acute infection.<br><br>METHODS: This retrospective cross-sectional study was conducted in 10 family medicine practices in Croatia. The data collected from medical records included demographics, COVID-19 vaccination status, SARS-CoV-2 infection history and severity, and documented health conditions before and after infection. Descriptive statistics were used to summarize the data. Group differences were analyzed using the independent samples t-test or &#x3c7;[2] test. Variables significant in univariate analyses (p&#x202f;<&#x202f;0.05) were included into multivariate regression models. Multiple linear regression was used to identify predictors of COVID-19 severity, and binary logistic regression was applied to determine factors associated with post-COVID conditions. Results are presented as regression coefficients (&#x3b2;) or odds ratios (OR) with 95% confidence intervals (CI). A p-value < 0.05 was considered statistically significant.<br><br>RESULTS: The study included 1,423 participants (58.0% female; mean age 52.6&#x202f;&#xb1;&#x202f;17.2&#x202f;years), of whom 82.4% had confirmed SARS-CoV-2 infection and 32.3% were unvaccinated. At least one chronic disease was present in 28.1% of participants. The most frequently reported post-COVID conditions were brain fog (4.9%), neurological disorders (4.7%), cardiovascular diseases (2.9%), shortness of breath (2.8%), obesity (2.7%) and mental health disorders (2.6%). Greater COVID-19 severity was independently associated with pulmonary disease (&#x3b2;&#x202f;=&#x202f;0.22; p&#x202f;=&#x202f;0.031) and older age, particularly 51-65&#x202f;years (&#x3b2;&#x202f;=&#x202f;0.31; p&#x202f;<&#x202f;0.001) and &#x2265;66&#x202f;years (&#x3b2;&#x202f;=&#x202f;0.50; p&#x202f;<&#x202f;0.001). COVID-19 vaccination was associated with milder disease (&#x3b2;&#x202f;=&#x202f;-0.21; p&#x202f;<&#x202f;0.001). Previous cardiovascular and musculoskeletal diseases significantly increased the risk of thromboembolism. Diabetes, obesity, and number of vaccine doses were predictors of brain fog, while neurological comorbidities predicted post-COVID mental health disorders.<br><br>CONCLUSION: Post-COVID symptoms and conditions represent an important long-term public health challenge. Family medicine physicians play a key role in early recognition, monitoring, and management of post-COVID sequelae, contributing to improved long-term patient outcomes.},
}
@article {pmid41695044,
year = {2026},
author = {Wang, X and Velásquez, E and Saydah, S and Koumans, EH and Rochlin, I and Romano, S and Rehkopf, DH and Ford, ND},
title = {Post-COVID-19 conditions identified by ICD-10-CM code in a cohort of U.S. primary care patients, 2021 - 2023.},
journal = {Journal of multimorbidity and comorbidity},
volume = {16},
number = {},
pages = {26335565261422426},
pmid = {41695044},
issn = {2633-5565},
abstract = {OBJECTIVES: Describe patient characteristics, healthcare utilization, and Post-COVID-associated conditions among primary care patients with an ICD-10-CM diagnosis code for Post COVID-19 Condition (U09.9).<br><br>METHODS: Using electronic health record (EHR) data from the American Family Cohort, a U.S. national primary care dataset, we identified patients with a U09.9 diagnosis documented October 1, 2021-June 1, 2023. Patient data were categorized into three periods: pre-pandemic (2016-2019), pandemic pre-index (2020 to the first U09.9 diagnosis, or 'index' date), and post-index (index date to the last observation). Post-COVID-associated conditions were aggregated a priori into 12 body systems.<br><br>RESULTS: We identified 10,265 patients with a U09.9 diagnosis code; 81.9% were &#x2265;40&#xa0;years, 63.3% female, 74.4% White, and 70.5% resided in metropolitan counties. Patients averaged 12.7 primary care encounters in the year before the index U09.9 diagnosis, compared to 9.2 encounters annually in the post-index period. Over 68% of patients who had &#x2265;1 pre-pandemic encounters had &#x2265;1 underlying medical conditions. The prevalence of conditions across 9 out of 12 body systems increased from the pre-pandemic to the pandemic pre-index period for patients who had &#x2265;1 conditions. Prevalence of respiratory and musculoskeletal conditions had the largest decrease from the pandemic pre-index to the post-index period.<br><br>CONCLUSIONS: Compared to adults who self-report Long COVID in nationally representative population-based surveys, patient characteristics in this cohort highlight a potential diagnosis gap - particularly for patients with rural residence or high county-level socioeconomic deprivation. Given frequent healthcare utilization and clinical complexity, primary care may require additional resources to meet patient needs.},
}
@article {pmid41694691,
year = {2026},
author = {Mallinson, PA and Birk, N and Henderson, AD and Lewin, A and Shah, AS and Mehrkar, A and Goldacre, B and Babu, GR and Banjara, SK and , and Tomlinson, LA and Kinra, S and Mathur, R},
title = {Ethnic differences in Long COVID diagnosed in primary care in England (2020-2022): an observational cohort study using OpenSAFELY.},
journal = {The Lancet regional health. Europe},
volume = {63},
number = {},
pages = {101605},
pmid = {41694691},
issn = {2666-7762},
support = {/WT_/Wellcome Trust/United Kingdom ; },
abstract = {BACKGROUND: Long COVID continues to affect millions of adults and contribute to substantial economic burden across Europe. Ethnic inequalities in Long COVID, and the reasons underlying these, are poorly understood. We aimed to investigate ethnic differences in the incidence of diagnosed Long COVID in England using linked national primary care data.<br><br>METHODS: With approval from NHS England, we used linked health record data from England, 2020-2022, accessed through the OpenSAFELY platform. We applied Cox regression to compare incidence of diagnosed Long COVID in primary care across self-reported ethnicity in five groups. We explored potential explanations for these differences by 1) adjusting for sociodemographic and health-related factors, 2) restricting to those tested or hospitalised with COVID-19, 3) stratifying into 16 ethnic sub-groups.<br><br>FINDINGS: Our sample comprised 17,848,825 adults, of whom 16,970 (0.1%) had a diagnosis of Long COVID recorded in primary care. Hazard ratios (95% confidence intervals) for Long COVID compared with the white group were 1.04 (0.98-1.11) for the South Asian group, 0.84 (0.75-0.94) for the Black group, 0.97 (0.84-1.13) for the Mixed Ethnicity group, and 0.63 (0.55-0.72) for Other ethnic groups, which remained similar when adjusting for sociodemographic and health-related factors and among those tested or hospitalised for COVID-19. Disaggregating into 16 ethnic sub-groups revealed heterogeneity within groups, for example, compared with the White British group, hazard ratios were 1.21 (1.00-1.47) for the Bangladeshi group and 1.09 (0.99-1.21) for the Pakistani group, but 0.77 (0.70-0.86) for the Indian group; and 1.15 (0.95-1.40) for the Black Caribbean group but 0.61 (0.51-0.72) for the Black African group.<br><br>INTERPRETATION: Differences in Long COVID diagnoses across broad ethnic groups mask important sub-group inequalities, offering insight into underlying mechanisms and approaches to better target Long COVID services.<br><br>FUNDING: The OpenSAFELY platform is principally funded by grants from: NHS England [2023-2025]; The Wellcome Trust (222097/Z/20/Z) [2020-2024]; MRC (MR/V015737/1) [2020-2021]. Additional contributions to OpenSAFELY and this analysis have been funded by grants from: MRC via the National Core Study programme, Longitudinal Health and Wellbeing strand (MC_PC_20030, MC_PC_20059) [2020-2022] and the Data and Connectivity strand (MC_PC_20058) [2021-2022]; NHS England via the Primary Care Medicines Analytics Unit [2021-2024]; NIHR and MRC via the CONVALESCENCE programme (COV-LT-0009, MC_PC_20051) [2021-2024] and MRC (MR/V040235/1) [2021-24].},
}
@article {pmid41693716,
year = {2026},
author = {Trbojević, T and Kovačević, A and Kukuruzović, M and Šeparović, I and Bašić Kes, V and Malenica, M},
title = {Neurological Symptoms as (Post) Pandemic Burden in Children and Adolescents-Single Tertiary Center Experience from Croatia.},
journal = {Iranian journal of child neurology},
volume = {20},
number = {1},
pages = {63-69},
pmid = {41693716},
issn = {1735-4668},
abstract = {OBJECTIVES: Although COVID-19 primarily affects the respiratory system, the central and peripheral nervous system may be involved. Neurological manifestations of COVID-19 infection occur in acute or post-acute stages and may persist as long-lasting symptoms known as "long-COVID" or "post-COVID-19". This study aimed to investigate the clinical profile, outcomes, and management of neurological manifestations after COVID-19 infection in children.<br><br>MATERIALS &amp; METHODS: A retrospective chart review was conducted of all pediatric patients admitted to our tertiary pediatric center with neurological symptoms following COVID-19, meeting criteria for long COVID-19/post-COVID-19, from December 2020 through the end of 2021, with a one-year follow-up period.<br><br>RESULTS: Eighty-four patients were included (median age 12.7 years; range, 0.5-18 years). Girls were more affected than the boys (female n = 51; 60.7%, &#x3c7;2 = 3, 86; p = 0,049). The most common neurological manifestation were headache (n = 47; 55.95%), dizziness (n = 19; 22.6%), visual disturbances (n = 9; 10.7%), afebrile seizures (n = 6; 7.1%), and anosmia/hyposmia (n = 4; 4.7%). Overall, 19 (22.6%) patients required psychological support, of whom 4 (4.8%) patients required psychiatric consultation due to suspected mental disorder. The most significant number of patients with neurological symptoms after COVID-19 was observed between October 2020 and March 2021 (n=44, 52.4%).<br><br>CONCLUSION: The obtained findings align with the results from similar studies and show that neurological manifestations after COVID-19 infection appear more frequently in school-aged children, predominantly in female patients. Neurological post-COVID-19 symptoms require medical attention to exclude more severe conditions.},
}
@article {pmid41690938,
year = {2026},
author = {Walders, J and Wetz, S and Costa, AS and Hofmann, A and Schulz, JB and Reetz, K and Dadsena, R},
title = {Longitudinal modeling of Post-COVID-19 condition over three years: A machine learning approach using clinical, neuropsychological, and fluid markers.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {6517},
pmid = {41690938},
issn = {2045-2322},
mesh = {Humans ; *Machine Learning ; *COVID-19/complications/psychology ; Female ; Middle Aged ; Longitudinal Studies ; Male ; Biomarkers ; Adult ; SARS-CoV-2/isolation &amp; purification ; Neuropsychological Tests ; Aged ; },
abstract = {Post-COVID-19 condition (PCC) manifests with prolonged, heterogeneous symptoms challenging both, diagnosis and therapeutic management. This three-year longitudinal study analyzed data from 93 adults (mean age of 48.9 ± 14.0, 60 female) after confirmed SARS-CoV-2 infection. Every follow-up visit included clinical, neuropsychological, and laboratory assessments, capturing multidimensional indicators of patient health. A machine learning framework was implemented to classify temporal stage of patient health status, identify visit-specific predictive markers, and manage incomplete data using both native handling in tree-based models and explicit imputation techniques. Gradient boosting methods consistently achieved the best performance across all visit comparisons, achieving F1-scores close to or above 90%. Classification performance improved with greater time intervals between visits, suggesting progressive divergence in patient phenotypes over time. For discriminating follow-up stages, inflammatory markers emerged as the most informative predictors, followed by SARS-CoV-2 antibody levels and neuropsychiatric measures for fatigue and cognitive performance. Interpretability analyses using SHAP and LIME confirmed the contribution of these features, while revealing shifts in feature relevance across years. These findings highlight the utility of machine learning in characterizing follow-up stage separability in PCC and offer clinically interpretable insights that prioritize immune and neuropsychological measures for monitoring and risk-stratified follow-up.},
}
@article {pmid41687822,
year = {2026},
author = {Zhou, T and Zhang, B and Zhang, D and Jhaveri, R and Chen, J and Becich, MJ and Castro, L and Chen, Y and Chilukuri, N and Herring, SJ and Lei, Y and Li, L and Lu, Y and Hornig, M and Khalsa, AS and Liebovitz, D and Mosa, ASM and Taylor, BW and Tedla, YG and Thodeson, D and Tong, J and Wu, Q and Forrest, CB and Chen, Y},
title = {Pre-COVID-19 body mass index and post-acute cardiovascular, gastrointestinal, and neuropsychiatric outcomes among children and young adults with SARS-CoV-2 infection: An EHR-based cohort study from the RECOVER Initiative.},
journal = {The Journal of infection},
volume = {92},
number = {3},
pages = {106702},
doi = {10.1016/j.jinf.2026.106702},
pmid = {41687822},
issn = {1532-2742},
abstract = {OBJECTIVES: Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems, but the role of preinfectional body mass index (BMI) in these outcomes among children and young adults remains unclear. We aimed to evaluate the association between pre-COVID-19 BMI status and post-acute cardiovascular, gastrointestinal, and neuropsychiatric outcomes in children and young adults.<br><br>METHODS: We conducted a retrospective cohort study using data from 139,320 individuals aged 5 to 20 years with confirmed SARS-CoV-2 infection between March 2020 and September 2023 across 20 U.S. pediatric health systems participating in the RECOVER Initiative. Pre-infection BMI was defined using measurements obtained within 18 months before the index date and categorized as healthy weight, overweight, obesity, or severe obesity; when multiple values were available, the most recent measurement was selected. We assessed incident post-acute cardiovascular, gastrointestinal, and neuropsychiatric symptoms and conditions occurring 28 to 179 days post-infection. Adjusted relative risks (RRs) were estimated using modified Poisson regression models, comparing elevated BMI categories to the healthy weight.<br><br>FINDINGS: Among 139,320 participants (mean [SD] age, 13.0 [4.3] years; 51.6% female), severe obesity was associated with a higher risk of cardiovascular disorders (adjusted RR 2.56; 95% CI 1.93-3.41), particularly hypertension (adjusted RR 3.68; 95% CI 2.65-5.11). Severe obesity was also linked with increased risks of diarrhea (adjusted RR 1.34; 95% CI 1.10-1.64) and gastroesophageal reflux disease (adjusted RR 1.29; 95% CI 1.06-1.58). Associations between BMI and neuropsychiatric outcomes were heterogeneous, with inverse associations observed for some conditions, including anxiety and major depression.<br><br>INTERPRETATION: In this cohort study, pre-COVID-19 BMI status was associated with the risk and pattern of post-acute cardiovascular and gastrointestinal outcomes among children and young adults. Association between pre-infection BMI and neuropsychiatric outcomes was more variable and should be interpreted with caution. These findings suggest BMI-stratified post-COVID-19 monitoring strategies may help inform long-term care in youth.},
}
@article {pmid41685877,
year = {2026},
author = {Fichera, A and Biancareddu, E and Bozzo, M and Ezenwa, M and Ongarini, EP and Ferrari, FG and Prefumo, F and Odicino, FE},
title = {Long COVID following SARS-CoV-2 infection during pregnancy: An observational study in a large Italian hospital during the COVID-19 pandemic.},
journal = {Acta obstetricia et gynecologica Scandinavica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aogs.70127},
pmid = {41685877},
issn = {1600-0412},
abstract = {INTRODUCTION: Despite mounting evidence on Long COVID, data regarding its impact on women infected during pregnancy remains scarce. This study aimed to assess the development of Long COVID in women who had been infected with SARS-CoV-2 during pregnancy, focusing on possible risk factors and potential protective elements associated with its development.<br><br>MATERIAL AND METHODS: We analyzed a cohort of 348 pregnant women with laboratory-confirmed SARS-CoV-2 infection admitted to ASST-Spedali Civili (Brescia, Italy) between March 2020 and May 2022. Data collection included demographics, comorbidities, COVID-19 severity markers, and vaccination status. To assess the possible association between the analyzed risk factors and Long Covid, beyond standard multivariable models, we employed inverse probability weighting techniques (IPTW) and calculated e-values to assess unmeasured confounding.<br><br>RESULTS: Among study participants, 27.0% (94/348) developed Long COVID. Risk factors included preexisting respiratory comorbidities (adjusted OR&#x2009;=&#x2009;3.171, 95% CI 0.99-10.1), pneumonia at admission (adjusted OR&#x2009;=&#x2009;4.48, 95% CI 2.16-9.28), and earlier pregnancy stage at infection (adjusted OR&#x2009;=&#x2009;0.96 per week, 95% CI 0.93-0.99). COVID-19 vaccination was associated with a significantly lower risk of Long COVID (15.5% in vaccinated vs. 31.8% in unvaccinated women; IPTW-adjusted OR&#x2009;=&#x2009;0.38, 95% CI: 0.20-0.71, p-value: 0.003). The most common symptoms were fatigue (46.8%) and memory impairment (38.3%), with unvaccinated patients exhibiting a higher prevalence of neuropsychiatric symptoms.<br><br>CONCLUSIONS: Our data suggest that one in four pregnant women hospitalized with COVID-19 develop persistent symptoms. The most frequently affected women had preexisting respiratory disease, pneumonia at admission, and infection earlier in pregnancy. COVID-19 vaccination appears to reduce risk and alter symptom presentation. These findings underscore the importance of vaccination throughout pregnancy and highlight the need for targeted surveillance in high-risk subgroups.},
}
@article {pmid41685290,
year = {2025},
author = {Jimenez, M and Lopez, M and Miller, J and Okubadejo, NU and Hurtado, C and Singh, AK and Ojo, OO and Rojas-Gualdron, DF and Akase, I and Agabi, OP and Kumar, K and Tomar, BS and Nathiya, D and Jules, R and Liotta, EM and Koralnik, IJ},
title = {A cross-continental comparative analysis of the neurological manifestations of Long COVID.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1760173},
pmid = {41685290},
issn = {1662-5161},
abstract = {OBJECTIVE: To compare demographics, comorbidities, neurologic symptoms, quality of life, and cognitive outcomes among adult individuals with neurologic manifestations of post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) across countries with varying income levels: the United States (U.S.), Colombia, Nigeria, and India.<br><br>METHODS: In this multi-country observational study, participants were evaluated in hospital clinics and recruited from institutional databases between 2020 and 2025. Patients were categorized as post-hospitalization Neuro-PASC (PNP) or non-hospitalized Neuro-PASC (NNP). Cognitive assessments were performed using the NIH Toolbox (U.S. and Colombia), the Montreal Cognitive Assessment (Nigeria), or the Mini-Mental State Examination (India).<br><br>RESULTS: A total of 3,157 participants were enrolled (652 PNP; 2,505 NNP). PNP patients were predominantly male except in the US, while NNP patients were predominantly female, except in India. The most frequent neurologic symptoms were brain fog, myalgia, dizziness, headache, and sensory disturbances, with frequency highest in the U.S. and lowest in India. There were significant differences for most neurologic and non-neurologic symptoms of PASC, driven by higher frequencies in U.S. and Colombia in both PNP and NNP cohorts. In addition, cognitive impairment measured with different instruments varied across countries for both PNP and NNP groups. Multiple correspondence analysis showed clustering of symptom burden between U.S./Colombia and Nigeria/India.<br><br>CONCLUSION: Neuro-PASC presents globally but symptom burden, and psychological distress vary across regions, likely influenced by sociocultural factors, healthcare access, and diagnostic tools. These findings highlight the need for culturally-adapted screening and post-COVID care worldwide.},
}
@article {pmid41683839,
year = {2026},
author = {Chen, JJ and Hsu, CW and Wang, HY and Stubbs, B and Chen, TY and Liang, CS and Chen, YW and Zeng, BS and Tseng, PT},
title = {Audiovestibular Dysfunction Related to Long COVID-19 Syndrome: A Systematic Review of Characteristics, Pathophysiology, Diagnosis, and Management.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
pmid = {41683839},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/physiopathology/diagnosis ; SARS-CoV-2 ; *Vestibular Diseases/diagnosis/therapy/physiopathology/etiology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID-19 syndrome (or so-called post-COVID-19) is indicated by miscellaneous symptoms, usually starting 3 months from the COVID-19 infection and lasting for at least 2 months, which cannot be explained by an alternative diagnosis. There has been more and more reports addressing the audiovestibular dysfunction related to long COVID-19 syndrome. Emerging evidence suggests that the linkage between audiovestibular dysfunction and long COVID-19 syndrome might rely on (a) direct inner ear system damage related to viral invasion and consequent inflammation, (b) micro thromboembolic events, which might result from the COVID-19-induced autoimmune reaction against endothelial cells, and consequent transient-ischemia and hypoxia of the auditory pathways, (c) the disturbed nerve conduction in vestibulocochlear nerves due to viral invasion, and finally (d) altered auditory cortex function, either imbalanced central gain or neurotransmitter disturbance. However, most of the aforementioned mechanism remained hypothetic and still needed further studies to approve or refute. This systematic review synthesizes current evidence on the characteristics, pathophysiology, diagnostic approaches, and management of audiovestibular dysfunction related to long COVID-19 syndrome. Literature searches across PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect (up to 15 December 2025) were conducted in accordance with PRISMA guidelines. Through this systematic review, we provided a schematic diagram of the physiopathology of long COVID-19 syndrome-related audiovestibular dysfunction. Further, we summarized the currently available diagnostic tools to explore the audiovestibular function in such patients. The currently available treatment, either pharmacotherapy or nonpharmacotherapy, mainly tackles idiopathic audiovestibular dysfunction but not specifically long COVID-19 syndrome-related audiovestibular dysfunction. Timely recognition and intervention may prevent progression to permanent hearing loss or vestibular disability, improving quality of life. Trial registration: PROSPERO CRD420251265741.},
}
@article {pmid41683343,
year = {2026},
author = {Kodama, S and Nakata, M and Konishi, N and Yoshino, M and Fujisawa, A and Naganuma, M and Kobayashi, Y and Hirai, Y and Kitagawa, A and Miyokawa, M and Mishima, R and Teramukai, S and Fukushima, M},
title = {Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial.},
journal = {Nutrients},
volume = {18},
number = {3},
pages = {},
pmid = {41683343},
issn = {2072-6643},
support = {n/a//Japanese Society for Vaccine Related Complications/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/etiology/drug therapy/blood ; *Vitamin D/blood/administration &amp; dosage/therapeutic use/analogs &amp; derivatives ; Male ; Female ; *Vitamin D Deficiency/drug therapy/complications/blood ; *COVID-19/complications/prevention &amp; control ; Middle Aged ; Adult ; Dietary Supplements ; SARS-CoV-2 ; *Vaccination/adverse effects ; *COVID-19 Vaccines/adverse effects ; Treatment Outcome ; },
abstract = {Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency. Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12. Results: Mean symptom change was -6.7 in the intervention group versus -1.2 in the control group (between-group difference -5.6; 95% CI: -7.2, -3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts. Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC.},
}
@article {pmid41682777,
year = {2026},
author = {Oz, A and Yildirim, T},
title = {Association Between Post-COVID-19 Infection and Fibromyalgia: A Controlled Case-Control Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {3},
pages = {},
pmid = {41682777},
issn = {2077-0383},
abstract = {Background: Persistent musculoskeletal pain has been increasingly reported following COVID-19 infection. However, the association between post-COVID-19 infection and fibromyalgia diagnosed using standardized criteria remains incompletely understood. Objective: This study aimed to investigate the association between post-COVID-19 infection and fibromyalgia diagnosed according to the 2016 American College of Rheumatology (ACR) criteria. Methods: In this case-control study, individuals with post-COVID-19 infection were compared with COVID-19-negative controls. Fibromyalgia was diagnosed using the ACR 2016 criteria. Clinical assessments were performed under standardized conditions. Patients with ongoing symptoms compatible with long COVID were excluded based on clinical evaluation. Results: The prevalence of fibromyalgia was significantly higher in participants with post-COVID-19 infection compared with controls. Individuals in the post-COVID group demonstrated higher odds of meeting ACR 2016 fibromyalgia criteria and exhibited greater symptom burden across clinical measures. These findings indicate a robust association between post-COVID-19 infection and subsequent fibromyalgia diagnosis. Conclusions: Post-COVID-19 infection was associated with an increased likelihood of fibromyalgia diagnosed using standardized criteria. While causality cannot be inferred due to the observational design, the findings highlight the importance of considering fibromyalgia in patients presenting with persistent musculoskeletal pain after COVID-19 and support further longitudinal and mechanistic research. These findings should be interpreted in light of the observational design and potential selection bias inherent to the case-control methodology.},
}
@article {pmid41676584,
year = {2026},
author = {Song, Y and Mehl, F and No, T and Livingston, L and Barbosa, JSQ and Hayashi, J and Serrero, G and Bortz, PS and Wilson, JM and Crowe, JE and Ho, DD and Yin, MT and Tan, J and Zeichner, SL},
title = {ACE-2-like Enzymatic Activity in Anti-SARS-CoV-2 Spike Protein Monoclonal Antibodies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41676584},
issn = {2692-8205},
support = {R01 AI176515/AI/NIAID NIH HHS/United States ; },
abstract = {Many people are affected by post-acute sequelae of COVID-19 (PASC/long COVID, LC). LC has severely affected public health. Features of LC including blood pressure dysregulation, coagulopathies, hyperinflammation, and neuropsychiatric complaints. Mechanisms responsible for LC pathogenesis are not clear. The receptor for SARS-CoV-2 is human angiotensin converting enzyme 2 (ACE2), which binds SARS-CoV-2 spike protein receptor-binding domain (RBD) to initiate infection. We hypothesized that some people produce anti-RBD antibodies that sufficiently resemble ACE2 structure to have ACE2-like catalytic activity. Those antibodies, ACE2-like abzymes, may contribute to LC pathogenesis. We previously showed that ACE2-like activity was associated with immunoglobulin in some people with acute and convalescent COVID-19. ACE2-like catalytic activity correlated with blood pressure changes following moderate exercise challenge in convalescents. We screened human monoclonal antibodies (mAbs) against SARS-CoV-2 spike protein from 4 sources. We identified 4 human mAbs with ACE2-like catalytic activity. The activity was not inhibited by MLN-4760, a compound that inhibits native human ACE2, 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 lower Vmax and Km values than ACE2. The data suggested that the antibodies cleave angiotensin II via a different mechanism than ACE2. Identification of 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.},
}
@article {pmid41675585,
year = {2026},
author = {Boskabadi, AR and Poorzand, H and Vaezi, A and Afshar, S and Tayyebi, M and Morovatdar, N},
title = {Increased Arrhythmia Risk in Long COVID: A Systematic Review and Meta-Analysis.},
journal = {Journal of arrhythmia},
volume = {42},
number = {1},
pages = {e70278},
pmid = {41675585},
issn = {1880-4276},
abstract = {BACKGROUND: COVID-19 infection can cause significant long-term health problems for patients. While there is no universally accepted definition for long COVID, it is usually identified by persistent symptoms that extend past 4 weeks after the initial SARS-CoV-2 infection with no other explanation. The cardiovascular system is one of the most important systems involved in long COVID, and even asymptomatic patients have evidence of cardiovascular injury after COVID-19. This study aims to determine the long-term risk of developing cardiac arrhythmias after SARS-CoV-2 infection.<br><br>METHODS: A comprehensive systematic search on Scopus, PubMed, Science Direct, and Web of Science databases was performed on August 24th, 2025. Cohort articles consisting of a healthy control group with no history of COVID-19 infection and individuals who recovered from COVID-19 for at least 30&#x2009;days were included. Hazard Ratio (HR) and 95% confidence intervals (CI) were estimated using random-effect models.<br><br>RESULTS: Fourteen studies were eligible for the meta-analysis. The overall arrhythmia risk was higher in patients with long COVID (HR: 1.74, 95% CI [1.39, 2.10], I [2]&#x2009;=&#x2009;99.65%). Specific arrhythmias examined included atrial fibrillation (HR: 1.49, 95% CI [1.24, 1.73], I [2]&#x2009;=&#x2009;98.57%), sinus tachycardia (HR: 1.69, 95% CI [1.21, 2.18], I [2]&#x2009;=&#x2009;99.51%), sinus bradycardia (HR: 1.58, 95% CI [1.50, 1.66], I [2]&#x2009;=&#x2009;65.80%), and ventricular arrhythmias (HR: 1.72, 95% CI [1.48, 1.95], I [2]&#x2009;=&#x2009;96.89%). Patients with a more severe initial infection were at a higher risk of developing arrhythmias.<br><br>CONCLUSIONS: The risk of developing cardiac arrhythmias is increased after COVID-19 infection in the long term.},
}
@article {pmid41675440,
year = {2026},
author = {Khurana, MP and Brünnich Sloth, MM and Scheidwasser, N and Curran-Sebastian, J and Morgenstern, C and Banholzer, N and Thein, D and Mortensen, LH and Rasmussen, M and Jokelainen, P and Møller, FT and Stegger, M and Krause, TG and Cameron, E and Duchêne, DA and Katsiferis, A and Bhatt, S},
title = {SARS-CoV-2 reinfections and subsequent risk of hospital-diagnosed post-acute sequelae in Denmark (2020-2022): a nationwide cohort study.},
journal = {The Lancet regional health. Europe},
volume = {63},
number = {},
pages = {101601},
pmid = {41675440},
issn = {2666-7762},
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC), or long COVID, are a public health concern. While most recover from SARS-CoV-2 infections within weeks, some experience persistent symptoms. Here, we quantified the association between repeated SARS-CoV-2 infections and the risk of hospital-diagnosed PASC.<br><br>METHODS: We conducted a nationwide register-based cohort study of all adults in Denmark (&#x2265;18 years) with at least one SARS-CoV-2 PCR or antigen test between April 1, 2020, and December 31, 2022. Participants were followed from first test until long COVID diagnosis (ICD-10: B948A), death, emigration, three SARS-CoV-2 infections, or end of study. Risk of long COVID diagnosis was estimated at three timepoints after study entry (180 days, 1 year, 2 years) and the outcomes were assessed during the 180 days after each timepoint. Cause-specific Cox models treated death as a competing risk, with number of infections and vaccination status as time-varying covariates. Absolute risks and differences were estimated using G-computation. Analyses were stratified by sex, income, and vaccination status. Secondary analyses assessed fatigue and headache (ICD-10), excluding individuals with prior diagnoses.<br><br>FINDINGS: Of 4,418,544 individuals, 6942 (0.16%) were diagnosed with long COVID. The absolute risk of a diagnosis increased following reinfection (0.73% [95% CI 0.69-0.77] after one infection vs. 1.16% [1.05-1.30] after two infections at 180 days), but differences were small and decreased over time. Risks following reinfection were similar across sex and income strata. Absolute risk decreased with prior vaccinations. Secondary analyses showed no increased risk of fatigue or headache after primary infection. A small increase in fatigue risk was observed after reinfection at 1 year (RD 0.03% [0.01-0.05]), but not for headache.<br><br>INTERPRETATION: Reinfection increases long COVID risk; however, the absolute increase after reinfection is smaller than that observed after a primary infection. Vaccination offers substantial protection against long COVID.<br><br>FUNDING: Danish National Research Foundation (DNRF).},
}
@article {pmid41674904,
year = {2025},
author = {Chen, J and Guo, D and Guo, X and Zhao, L and Li, G and Liu, H and Wang, S and Lao, Z and Zhu, M},
title = {Broad-spectrum inhibition of SARS-CoV-2 variants by dibutyl phthalate through allosteric disruption of Spike-ACE2 interface.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1610775},
pmid = {41674904},
issn = {1664-302X},
abstract = {INTRODUCTION: The persistent evolution of SARS-CoV-2 has diminished the efficacy of existing vaccines and antibodies, increasing the risks of reinfection and Long COVID. There is a significant need for the development of convenient, broad-spectrum antiviral agents that target the early stage of viral infection. Traditional Chinese Medicine (TCM) volatile oils, with their diverse components and suitability for nasal delivery, demonstrate potential against respiratory viruses. This study aimed to screen bioactive compounds from TCM volatile oils for their ability to inhibit the interaction between the SARS-CoV-2 spike (S) protein and its host receptor, ACE2.<br><br>METHODS: A virtual screening of 47 structurally diverse TCM volatile compounds was performed to identify potential inhibitors of the Spike-ACE2 interaction. The top candidate, dibutyl phthalate (DBP), was further evaluated using in vitro assays including Spike-mediated membrane fusion and pseudovirus infection. Its mechanism was investigated through ELISA, surface plasmon resonance (SPR), ACE2 enzymatic activity assays, molecular docking. To evaluate its broad-spectrum potential, membrane fusion assays were further performed using spike proteins from the wild-type (WT), Delta, and Omicron XBB.1.5 variants. Critical binding residues were identified through molecular docking and subsequently confirmed by site-directed mutagenesis of the Spike receptor-binding domain (RBD).<br><br>RESULTS: Virtual screening identified ten potential inhibitors, with dibutyl phthalate (DBP) showing the strongest activity. DBP effectively inhibited S protein-mediated membrane fusion (IC 50 = 64.53 &#x3bc;M) and pseudovirus infection (IC 50 = 73.06 &#x3bc;M) with specificity. SPR analysis confirmed that DBP competitively inhibited the binding between the S trimer and ACE2 (increasing the K D from 8.28 nM to 86.7 nM). Mechanistic studies revealed that DBP disrupts the S-ACE2 interaction by targeting the receptor-binding domain (RBD) without affecting ACE2 enzymatic activity. Furthermore, DBP exhibited broad-spectrum inhibitory activity against membrane fusion mediated by the Delta (IC 50 = 49.22 &#x3bc;M) and Omicron XBB.1.5 (IC 50 = 53.70 &#x3bc;M) spike variants. Molecular docking and subsequent site-directed mutagenesis identified Tyr453 and Tyr495 as critical residues for DBP binding and its inhibitory function.<br><br>DISCUSSION: This study elucidates for the first time that DBP functions as a broad-spectrum RBD inhibitor. It binds to the RBD-ACE2 interface, dependent on conserved residues Tyr453 and Tyr495, and acts primarily through steric hindrance to block the Spike-ACE2 interaction. Notably, DBP shares critical aromatic and ester groups with other active-site inhibitors. Structure-activity relationship analysis of its derivatives revealed that introducing additional hydrogen-bond acceptors significantly enhances inhibitory activity, providing a clear structure optimization strategy. While DBP has known toxicity, its antiviral potential may be harnessed through strategic delivery approaches or SAR-guided optimization to advance its development against SARS-CoV-2 variants.},
}
@article {pmid41674460,
year = {2026},
author = {McTiernan, K and Hughes, C and Gilheaney, &#xd3;},
title = {Cognitive Communication, Voice and Swallowing Difficulties Experienced by Adults With Long-COVID: A Scoping Review.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {1},
pages = {e70595},
pmid = {41674460},
issn = {1369-7625},
mesh = {Humans ; *COVID-19/complications ; *Deglutition Disorders/etiology ; *Voice Disorders/etiology ; *Communication ; Adult ; SARS-CoV-2 ; *Communication Disorders/etiology ; },
abstract = {BACKGROUND: Adults with Long-COVID frequently experience impairments in cognitive-communication, voice and swallowing, however, few comprehensive reviews of the existing literature has yet to be conducted to map the current research landscape. To go some way toward addressing this gap, this scoping review collected and analysed relevant published studies to identify reported symptoms related to cognitive communication, voice and swallowing in post COVID-19 patients and the assessments used to identify these difficulties.<br><br>OBJECTIVE: This study aimed to systematically map the existing literature on cognitive-communication, voice and swallowing difficulties in individuals living with Long-COVID and the assessments used to identify these difficulties.<br><br>METHODS: Four databases were searched to identify original research articles aligned with the study's objectives. Studies meeting the inclusion criteria were selected, and the findings were analysed with a specific focus on three key symptom domains: cognitive-communication, voice and swallowing.<br><br>RESULTS: Nineteen studies met the inclusion criteria. A broad range of assessments were used, and a broad range of symptoms were identified related to cognitive-communication, voice and swallowing difficulties in patients with Long-COVID-19. The symptoms reported most frequently in the selected studies included memory deficits, incomplete or inefficient glottic closure, paradoxical vocal fold motion during inspiration, episodes of choking, globus sensation, premature spillage and pyriform sinus residue.<br><br>CONCLUSION: Despite limited prior research in this area, the findings underscore the significant impact that COVID-19 infection may have on cognitive communication, voice and swallowing functions. Post-COVID-19 patients report a wide array of challenges in these domains. As a result, further clinical research is essential to develop patient-centred care strategies and to equip healthcare professionals with the expertise required for effective management of this group of patients.},
}
@article {pmid41670237,
year = {2026},
author = {Clarke, J and Jha, S and Prociuk, D and Mayer, E and de Lusignan, S and Smith, N and Milne, R and Lee, C and Kock, J and Sivan, M and Delaney, BC and , },
title = {Exploring the Intensity and Continuity of Hospital Care for Patients With Long Covid: Evidence From an English Urban Healthcare System.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {1},
pages = {e70527},
pmid = {41670237},
issn = {1369-7625},
support = {//This study was supported by the National Institute for Health and Care Research. This work is supported by grants from the National Institute for Health and Care Research (NIHR - Ref: COV-LT2-0016) and NHS England. JC acknowledges funding from the Wellcome Trust (215938/Z/19/Z). The views expressed in this publication are those of the authors and not necessarily those of NIHR, The Department of Health and Social Care, or NHS England./ ; },
mesh = {Humans ; *COVID-19/therapy/epidemiology ; Retrospective Studies ; *Continuity of Patient Care/statistics &amp; numerical data ; Male ; Female ; Middle Aged ; London/epidemiology ; Aged ; Adult ; Secondary Health Care/statistics &amp; numerical data ; SARS-CoV-2 ; Hospitalization/statistics &amp; numerical data ; *Urban Health Services/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Long Covid (LC) is a multisystem condition leading to a wide range of symptoms and often requiring treatment by several different clinical specialties. Patients with LC have reported difficulties in accessing care and a lack of coordination of their care, particularly in a hospital setting.<br><br>OBJECTIVE: To determine the extent to which the intensity and continuity of hospital care changes for patients after they receive an LC diagnosis.<br><br>DESIGN: Retrospective observational cohort study using a linked primary and secondary care dataset.<br><br>SETTING AND PARTICIPANTS: Routine healthcare data from North West London Integrated Care System of patients with a recorded diagnosis of LC who had attended a secondary care hospital Trust from 1 January 2019 to 30 September 2023.<br><br>MAIN VARIABLES STUDIED: The intensity of utilisation of secondary care was calculated, and the continuity of care with respect to hospitals and specialties was computed using the sequential continuity score (SeCon) before the Covid-19 pandemic, before and after an LC diagnosis.<br><br>RESULTS: 5611 out of 6270 (90.1%) patients diagnosed with LC had a recorded secondary care interaction in the study period. Intensity of secondary care utilisation increased markedly in outpatient, inpatient and Emergency Department pathways after a diagnosis of LC but peaked in the week of diagnosis. Average hospital SeCon fell significantly after an LC diagnosis from 1.00 to 0.83, while specialty SeCon remained unchanged from after diagnosis (0.40) and before the pandemic (0.44). A notable shift in specialty activity was observed with a focus on respiratory medicine as a major hub in a densely connected patient-sharing network with cardiology and other medical and surgical specialties.<br><br>DISCUSSION: A recorded LC diagnosis was associated with increases in the intensity of hospital activity and a reduction in hospital-level care continuity, but no change in specialty continuity, which remains low.<br><br>CONCLUSION: Collectively, this indicates a significant need to support LC patients as they navigate fragmented secondary care pathways.<br><br>This study was co-designed with, conducted with and written in conjunction with people with long Covid.},
}
@article {pmid41668172,
year = {2026},
author = {Kim, DY and Youn, J and Kang, N and Cho, SI and Ha, IH},
title = {Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07807-w},
pmid = {41668172},
issn = {1479-5876},
abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.<br><br>METHODS: We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12&#x2009;weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.<br><br>RESULTS: The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n&#x2009;=&#x2009;8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.<br><br>CONCLUSION: Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.},
}
@article {pmid41667155,
year = {2026},
author = {Charlton, BT and Janssen, K and Systrom, DM and Putrino, D and Wüst, RC},
title = {Post-exertional malaise and the myth of cardiac deconditioning: rethinking the pathophysiology of long covid.},
journal = {British journal of sports medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjsports-2025-111387},
pmid = {41667155},
issn = {1473-0480},
}
@article {pmid41666312,
year = {2026},
author = {Kaushal, S and Bhandal, J and Birks, P and Greiner, J and Levin, A and Malbeuf, M and Schwartz, Z},
title = {Use of a Specialist Telephone Consultation Line for Long COVID in Primary Care in British Columbia: Retrospective Descriptive Quality Improvement Study.},
journal = {JMIRx med},
volume = {7},
number = {},
pages = {e57021},
pmid = {41666312},
issn = {2563-6316},
abstract = {BACKGROUND: Long COVID (post-COVID-19 condition) continues to challenge primary care. To support family physicians in British Columbia, the general internal medicine (GIM) COVID-19 Rapid Access to Consultative Expertise (RACE) line was launched in August 2020 to provide real-time specialist advice.<br><br>OBJECTIVE: This quality improvement study aimed to evaluate the implementation and utilization of the GIM-COVID-19 Long-Term Sequelae RACE line in British Columbia. Specifically, it sought to characterize the demographics of patients involved in RACE consultations, identify the most common themes and clinical queries presented by primary care providers, and assess how usage patterns evolved over time during the COVID-19 pandemic.<br><br>METHODS: We conducted a retrospective descriptive analysis of 149 RACE line call summaries between August 2020 and June 2021. Six calls were excluded due to insufficient information, such as incomplete documentation or absence of a clear COVID-19-related question. Because the original extraction notes are no longer available, further details about these calls cannot be provided, leaving 143 eligible calls. Data extracted included patient age, sex, geographical location, symptom type, and timing of symptom onset post-COVID-19 infection. Calls were categorized by symptom duration (acute: <2 wk, subacute: 2-12 wk, chronic: >12 wk), thematic content (respiratory, fatigue, neurological, etc), and query type (symptom management, return-to-work, vaccination, etc). Data were coded independently by two reviewers using a standardized spreadsheet and predefined codebook. Discrepancies were resolved through discussion. Descriptive statistics summarized the findings.<br><br>RESULTS: Many calls involved female patients (91/143, 64%), with the most common age group being 40-49 years (32/113, 28%). Most calls came from Greater Vancouver (35/83, 42%) and the Fraser Valley (29/83, 35%). Subacute symptoms (52/149, 35%) and vaccination-related concerns (29/149, 19%) were the most common inquiry types. Symptom-related inquiries accounted for 92 of 143 calls (64%), with 253 symptoms documented overall. Respiratory symptoms were most common (100/253, 40%), especially shortness of breath (35 calls), cough (26), and fatigue (23). Call volumes peaked from January to June 2021, coinciding with the provincial vaccine rollout.<br><br>CONCLUSIONS: The GIM-COVID-19 Long-Term Sequelae RACE line served as a critical early support system for primary care providers as the long COVID landscape evolved. This quality improvement study emphasizes the value of rapid access and specialist-informed consultation tools during emerging public health challenges. The trends ascertained may inform future health system responses, particularly when designing more scalable, interdisciplinary models to support primary care in managing complex chronic conditions.},
}
@article {pmid41663609,
year = {2026},
author = {Barnden, L and Baraniuk, J and Inderyas, M and Eaton-Fitch, N and Marshall-Gradisnik, S and Thapaliya, K},
title = {Impaired brain intrinsic connectivity in long COVID during cognitive exertion revealed by independent component analysis.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41663609},
issn = {2045-2322},
abstract = {Cognitive dysfunction is a symptom of Long COVID. To characterize functional connectivity changes that may contribute to cognitive dysfunction in Long COVID (LCov), two consecutive 450 s functional magnetic resonance imaging (fMRI) scans (Runs 1 and 2) were acquired on a 7 Tesla MRI scanner. During both, the Stroop colour-word task engaged intrinsic brain networks for conflict detection, conflict resolution and response execution. In this exploratory study we acquired data from 19 LCov and 16 healthy control (HC) participants. The aggregate dataset was subjected to independent component analysis (ICA) for each run to isolate 15 components with distinct spatial and temporal signatures. For each component we tested (1) for differences between LCov and HC (inter-network) connectivity to the rest of the brain and (2) for correlation of LCov connectivity with illness duration. Stroop response times (RTs) were slower in LCov than in HC in both Runs (p = 0.001, 0.003). Each ICA component occupied the hubs of a known intrinsic network. LCov had different inter-network connectivity to HC for Salience, Language, Central Executive, Sensorimotor and Visual networks. LCov deficits in Salience inter-network connectivity in Run 2 were deeper and more widespread than in Run 1. In contrast, Run 2 connectivity was greater in LCov for the angular gyrus which integrates visual, motor and language inputs and responses. With longer illness duration, LCov connectivity weakened to critical networks but showed compensatory effects in Lingual gyri. Slower Stroop RTs in both Runs, and Salience, Language and Central Executive inter-network connectivity deficits, and illness duration dependence, support cognitive impairment in LCov with some compensatory connectivity increases.},
}
@article {pmid41663412,
year = {2026},
author = {Wu, SI and Lin, CJ and Lin, YJ and Lin, IC and Hwang, LC and Chen, WL},
title = {Efficacy of heat-treated Lacticaseibacillus paracasei PS23 for individuals with long coronavirus disease-19 syndrome: a double-blinded randomized control pilot study.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {5368},
pmid = {41663412},
issn = {2045-2322},
support = {R21 MH110110/MH/NIMH NIH HHS/United States ; MMH-113-19, MMH-MM-11103, MMH-111-51, MMH-MM-11002, MMH-110-110, MMH-109112, MMH-10914//Department of Medical Research, Mackay Memorial Hospital/ ; IAC-11302//University-Industry Cooperation Fund, Mackay Memorial Hospital, Taipei, Taiwan/ ; },
abstract = {UNLABELLED: Long coronavirus disease (long COVID) refers to symptoms that persist beyond the acute phase of SARS-CoV-2 infection. This study applied the World Health Organization (WHO) definition, which identifies post-COVID-19 condition as symptoms lasting at least two months and beginning around three months after confirmed infection. Given limited evidence on probiotic use for long COVID, we conducted a double-blind, randomized, placebo-controlled trial to evaluate the effects of heat-treated Lacticaseibacillus paracasei PS23 (HT-PS23) in individuals with confirmed COVID-19 and self-reported prolonged symptoms. Thirty-nine eligible participants were randomly assigned to receive either the heat-treated Lacticaseibacillus paracasei PS23 (HT-PS23) or placebo for six weeks. Assessments included validated neuropsychological tests (including executive function and working memory using Color Trails 1&amp;2 and Digit Span and Coding), self-reported symptom scales of depression, anxiety, and quality of life, and blood biomarkers related to inflammation, immune response, and stress (e.g. cortisol, IFN-γ zonulin). After the six-week trial, HT-PS23 group showed notable improvements in cortisol level (p = 0.006), a reduction in errors of CTT2 (p = 0.018), and symptom severity related to breathing difficulties (p = 0.016) and appetite loss (p = 0.030) compared to the placebo group. HT-PS23 may be a feasible and well-tolerated intervention for relieving cognitive or physical symptoms associated with long COVID. Further studies with larger samples are warranted.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-27036-3.},
}
@article {pmid41662153,
year = {2026},
author = {Sirotiak, Z and Amro, HJ and Thomas, EBK},
title = {The lived experience of long COVID: A thematic analysis of an in-depth interview study.},
journal = {PLOS mental health},
volume = {3},
number = {2},
pages = {e0000500},
pmid = {41662153},
issn = {2837-8156},
abstract = {Long COVID is associated with significant physical and mental health burden, resulting in substantial quality of life limitations. The lived experience of individuals with long COVID is a vital consideration in evaluating the impact of the condition. Thirty-four adults with self-reported long COVID participated in a semi-structured in-depth interview study. An interview guide assessed physical and mental health symptoms, changes to plans, goals, and beliefs, and social impacts of long COVID. Participants were an average age of 51.6 years (SD = 17.0), and most identified as female (61.8%), white (97.1%), and not Hispanic or Latino/a/e (97.1%). Two coders read each interview while creating a codebook. The coders individually coded each interview transcript with themes emerging from the coded interviews. Each code reached an agreement level of at least 80%, with a Kappa (RK) score range of 0.90 to 0.98 in each interview, indicating adequate interrater reliability. Five themes emerged from the thematic analysis: decreased autonomy, decreased trust, changes in worldview, social impacts, and uncertainty. Individuals with long COVID reported heterogenous experiences, with often significant changes to daily functional abilities and outlook on life. Considering the unique lived experiences of individuals with long COVID will be important in developing a complete understanding of the condition and its implications.},
}
@article {pmid41657438,
year = {2026},
author = {Tervo, JP and Jacobson, PT and Vilarello, BJ and Saak, TM and Caruana, FF and Gallagher, LW and Gary, JB and Gudis, DA and Joseph, PV and Choo, TH and Devanand, DP and Goldberg, TE and Overdevest, JB},
title = {Interrelatedness of Neurocognitive Domain Functioning Between Unprompted and Prompted Identification Testing With Psychophysical Olfactory Evaluation in a Post-COVID-19 Cohort.},
journal = {World journal of otorhinolaryngology - head and neck surgery},
volume = {12},
number = {1},
pages = {56-65},
pmid = {41657438},
issn = {2589-1081},
abstract = {OBJECTIVE: Assessment of olfactory function with psychophysical testing requires cognitive demand to correctly pair test odors with remembered scents. Individuals suffering from long-Corona Virus Disease 2019 (long-COVID-19) may develop a decline in neurocognitive performance, which may be concurrent with persistent olfactory dysfunction (OD). Given the rigorous cognitive demand of the unprompted identification (UI) olfactory assessment, the goal of this study is to understand whether it could serve as a proxy for specific neurocognitive domains during clinical assessment of olfaction.<br><br>METHODS: Participants from our long-COVID cohorts with persistent OD underwent a panel of neurocognitive screening followed by olfactory assessment of threshold followed by unprompted (UI) and prompted identification (PI) tests using Sniffin' Sticks. Hierarchical linear mixed-effect models were used to understand the relative impact of each neurocognitive variable after controlling for demographics and olfactory threshold scores.<br><br>RESULTS: Neurocognitive variables demonstrated common correlation trends. Models containing Montreal Cognitive Assessment (MoCA) and digit-span backward scores had statistically significant fits for both UI (MoCA: &#x3c7; [2]&#x2009;=&#x2009;10.20, p&#x2009;=&#x2009;0.001/digit-span backward: &#x3c7; [2]&#x2009;=&#x2009;4.27, p&#x2009;=&#x2009;0.04) and PI (MoCA: &#x3c7; [2]&#x2009;=&#x2009;4.51, p&#x2009;=&#x2009;0.03/digit-span backward: &#x3c7; [2]&#x2009;=&#x2009;5.04, p&#x2009;=&#x2009;0.02) linear mixed-effect models, but UI was further explained by logical memory (&#x3c7; [2]&#x2009;=&#x2009;7.84, p&#x2009;=&#x2009;0.005), verbal fluency (&#x3c7; [2]&#x2009;=&#x2009;8.79, p&#x2009;=&#x2009;0.003), and digit-span forward (&#x3c7; [2]&#x2009;=&#x2009;12.30, p&#x2009;=&#x2009;0.0004). These relationships were statistically significant after controlling for demographic and olfactory threshold covariates.<br><br>CONCLUSIONS: UI and PI have interrelated neurocognitive dependence on global cognition (MoCA) and executive function (digit-span backward) among long-COVID participants. As UI draws upon neurocognitive domains of episodic (logical memory), semantic (verbal fluency), and working memory (digit-span forward), the inclusion of a UI task may provide supplementary screening for cognitive impairments in those undergoing clinical olfactory assessment, particularly among those with lingering effects of COVID-19.},
}
@article {pmid41656367,
year = {2026},
author = {Batur, ZZ and Delaruelle, K and Mortelmans, D and Dykstra, P and Bracke, P and Vergauwen, J},
title = {The long-term effects of the COVID-19 pandemic on loneliness in European older women and men: a growth curve analysis.},
journal = {European journal of ageing},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10433-025-00901-w},
pmid = {41656367},
issn = {1613-9372},
support = {TD/231/DistantButClose//Belgian Federal Science Policy Office/ ; },
abstract = {This study examines the long-term impact of the COVID-19 pandemic on loneliness among adults aged 65 and over across 27 European countries, focusing on gender differences and the role of government-imposed containment measures. Using longitudinal data from four waves of the Survey of Health, Ageing and Retirement in Europe (SHARE), pre-pandemic (Wave 8), two SHARE Corona surveys (2020-2021), and post-pandemic (Wave 9), the analyses include 49,351 observations from 15,497 individuals. Logistic growth curve models (wave-individual-country) were estimated to assess changes in loneliness across pandemic periods and to explore how gender and policy stringency shaped these patterns. The results show that loneliness increased significantly during the second COVID-19 phases and remained elevated in the post-pandemic period compared with pre-pandemic levels, indicating a sustained rise in emotional vulnerability among older adults, especially for women. Higher policy stringency was associated with greater loneliness, following a curvilinear pattern: Loneliness rose with increasing restriction levels but leveled off and declined at the highest stringency levels. Interaction analyses showed that women were more sensitive to increases in policy stringency. The findings underscore the persistent and gendered effects of the COVID-19 pandemic on loneliness among Europe's older population. Public health and social policy interventions should adopt gender-sensitive and context-aware approaches to reduce loneliness and enhance resilience during and after large-scale crises.},
}
@article {pmid41654702,
year = {2026},
author = {Vargas, C and Moges, R and Caltabellotta, G and David, L and Manalili, N and Tseng, M and Marlow, EC and Lent, AB},
title = {Exploring the Role of Race/Ethnicity, Metropolitan Status, and Health Insurance in Long COVID Among U.S. Adults.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {41654702},
issn = {2196-8837},
support = {5T34GM149492/GM/NIGMS NIH HHS/United States ; },
abstract = {OBJECTIVES: Limited evidence suggests possible disparities in COVID-19 across race/ethnicity, metropolitan status, and healthcare access. This study investigated racial/ethnic, metropolitan, and healthcare access disparities in Long COVID among U.S. adults.<br><br>METHODS: 2022-2023 cross-sectional Behavioral Risk Factor Surveillance System data were analyzed. U.S. adults who had COVID-19 were included, resulting in a final weighted sample size of n&#x2009;=&#x2009;80,093,998. Logistic regressions examined associations between race/ethnicity, metropolitan status, health insurance and ever or currently experiencing Long COVID and reductions in daily function. Interactions were examined for metropolitan status and health insurance.<br><br>RESULTS: Versus non-Hispanic White (NHW) respondents, a higher odds of Long COVID were observed for Non-Hispanic American Indian/Alaskan Native (ever adj. OR&#x2009;=&#x2009;1.24, 95% CI: 1.01, 1.53; currently adj. OR&#x2009;=&#x2009;1.72, 95% CI: 1.39, 2.12) and Other Race/Multiracial (ever adj. OR&#x2009;=&#x2009;1.41, 95% CI: 1.18, 1.62; currently adj. OR&#x2009;=&#x2009;1.35, 95% CI: 1.16, 1.58) respondents. Black (ever adj. OR&#x2009;=&#x2009;0.84, 95% CI: 0.76, 0.93), Asian (ever adj. OR&#x2009;=&#x2009;0.54, 95% CI: 0.42, 0.70), and Native Hawaiian/Pacific Islander (currently adj. OR&#x2009;=&#x2009;0.61, 95% CI: 0.39, 0.95) respondents had a lower odds. Non-metropolitan residents had a higher odds (ever adj. OR&#x2009;=&#x2009;1.16, 95% CI: 1.08, 1.25; currently adj. OR&#x2009;=&#x2009;1.16, 95% CI: 1.08, 1.24) versus metropolitan residents. Uninsured respondents had a higher odds versus insured respondents (currently adj. OR&#x2009;=&#x2009;1.24, 95%: 1.08, 1.44). Interactions were statistically significant for metropolitan status (ever p-value&#x2009;=&#x2009;0.026) and health insurance (ever p-value&#x2009;=&#x2009;0.006; currently p-value&#x2009;=&#x2009;0.008).<br><br>CONCLUSIONS: Long COVID is experienced unequally across race/ethnicity and metropolitan/non-metropolitan residence. Further research is needed to understand this heterogeneity and the effects of Long COVID.},
}
@article {pmid41654652,
year = {2026},
author = {Matits, L and Schellenberg, J and Mack, M and Kolassa, IT and Schilling, C and Rothenbacher, D and Peter, RS and Kern, WV and Nieters, A and Steinacker, JM and Bizjak, DA and , },
title = {Circulating mitochondrial and cellular damage markers in long COVID: Links to cognitive function, psychological distress, and inflammation.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41654652},
issn = {1476-5578},
support = {MR/S028188/1//Ministerium f&#xfc;r Wissenschaft, Forschung und Kunst Baden-W&#xfc;rttemberg (Ministry of Science, Research and Art Baden-W&#xfc;rttemberg)/ ; },
abstract = {Persistent mitochondrial inflexibility and mitochondrial damage may contribute to Post-Acute Sequelae of COVID-19 (PASC). However, data linking mitochondrial biomarkers, such as circulating cell-free mitochondrial DNA (ccf-mtDNA) to long-COVID symptoms remain limited. We analyzed ccf-mtDNA relative to glycerinaldehyd-3-phosphat-dehydrogenase and total cell-free DNA (ccf-DNA) in a nested case-control study of 228 adults (PASC: n = 128, recovered controls: n = 100). Possible associations between these markers and general cognition, verbal memory, psychological distress, and inflammation were also examined. ccf-DNA (measured via UV-Vis spectroscopy), relative ccf-mtDNA (measured via quantitative real-time PCR, -ΔCT), C-reactive protein [CRP], and systemic immune-inflammation index [SII] were assessed. Principal component analysis (PCA) was applied to (neuro)psychological tests to derive three components: general cognition, verbal memory, and psychological distress, which were used in further analyses. PASC patients exhibited significantly lower cognitive function and higher psychological distress than recovered controls. They also had elevated CRP levels and lower relative ccf-mtDNA, with 25% showing low-grade inflammation. Across all participants, general cognition correlated positively with the relative ccf-mtDNA, while CRP correlated negatively with the relative ccf-mtDNA. Mediation analysis suggested relative ccf-mtDNA as a potential mediator of CRP differences between PASC and recovered controls. However, CRP differences did not remain after controlling for potential confounders (age, sex, education, smoking, body mass index, psychiatric medication). Lower relative ccf-mtDNA in PASC might indicate altered mitochondrial quality control, potentially leading to mitochondrial dysfunction, accumulation of damaged mitochondria, and increased inflammation.},
}
@article {pmid41654387,
year = {2026},
author = {Pérez-Martínez, L and Romero, L and Palacios, E and Barbero, R and Moreno-Blanco, A and Del Campo, R and Blanco, JR},
title = {Oral microbiota in patients with long COVID: A pilot study.},
journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)},
volume = {44},
number = {2},
pages = {503072},
doi = {10.1016/j.eimce.2026.503072},
pmid = {41654387},
issn = {2529-993X},
mesh = {Humans ; Pilot Projects ; Male ; Female ; *COVID-19/microbiology/complications ; Case-Control Studies ; Middle Aged ; Saliva/chemistry/microbiology ; *Microbiota ; *Mouth/microbiology ; Fatty Acids, Volatile/analysis ; Adult ; Interleukin-6/analysis ; Aged ; Tumor Necrosis Factor-alpha/analysis ; Cytokines/analysis ; },
abstract = {INTRODUCTION: The COVID-19 pandemic continues to pose a substantial threat to global public health. While most efforts have focused on the acute phase SARS-CoV-2 infection, a significant proportion of individuals experience persistent symptoms after infection, known as "persistent COVID disease" (PCD). The etiology of PCD remains poorly understood, although some evidence suggests that microbiota, particularly those located in the upper respiratory tract, may play a role. The aim of this study was to investigate differences in the composition of the oral microbiota, salivary cytokine, and short-chain fatty acids (SCFAs) concentration, between PCD and healthy controls.<br><br>METHODS: We conducted an age- and sex-matched case-control study. Oral bacterial communities were profiled by 16S rDNA gene (V3-V4) amplicon high-throughput sequencing. Salivary IL-6 and TNF-&#x3b1; concentrations were measured, and SCFA were quantified by liquid chromatography-tandem mass spectrometry. Cognitive and fatigue status were assessed with the Montreal Cognitive Assessment (MoCA) and the Modified Fatigue Impact Scale (MFIS).<br><br>RESULTS: Oral-microbiota &#x3b1;/&#x3b2;-diversity did not differ between groups; salivary cytokines were likewise similar. After Benjamini-Hochberg correction, no SCFA differences were significant (q>0.05); valeric acid showed the strongest uncorrected signal (p=0.02; r=0.52) but not after adjustment (q=0.23; power &#x2248;0.73). CPD participants had lower MoCA and higher MFIS scores than controls (both p<0.005).<br><br>CONCLUSIONS: The increase of valeric acid levels in PCD patients warrants further investigation to clarify its potential biological role and implications in the pathophysiology of this syndrome.},
}
@article {pmid41651528,
year = {2026},
author = {Lee, HW and Choi, KY and Lee, JK and Yoon, WS and Kim, Y and Yoo, KH and Hwang, YI},
title = {Recurrent COVID-19 infection and the risk of exacerbation, mortality and long covid in patients with chronic obstructive pulmonary disease: a nationwide retrospective cohort study.},
journal = {BMJ open},
volume = {16},
number = {2},
pages = {e112376},
pmid = {41651528},
issn = {2044-6055},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/mortality/complications/epidemiology ; *COVID-19/mortality/epidemiology/complications ; Retrospective Studies ; Male ; Female ; Middle Aged ; Republic of Korea/epidemiology ; Aged ; Recurrence ; SARS-CoV-2 ; Disease Progression ; Risk Factors ; Symptom Flare Up ; Adult ; },
abstract = {OBJECTIVES: To evaluate how recurrent COVID-19 infections influence the clinical course of patients with chronic obstructive pulmonary disease (COPD), focusing on moderate-to-severe symptom flare-ups, all-cause mortality and long covid.<br><br>DESIGN: Nationwide retrospective cohort study.<br><br>SETTING: Korean Health Insurance Review and Assessment database covering the entire Korean population between January 2020 and December 2023.<br><br>PARTICIPANTS: A total of 313 760 patients aged &#x2265;40 years who met an established operational definition of COPD based on diagnostic codes and inhaled therapy prescriptions. Patients were stratified by the number of COVID-19 events: none, one, two or three or more.<br><br>The primary outcomes were moderate-to-severe COPD exacerbations and all-cause mortality. The secondary outcome was long covid, defined by WHO criteria using International Classification of Diseases (ICD)-10 codes persisting &#x2265;2 months within 3 months after infection.<br><br>RESULTS: Among 313 760 patients, 154 095 (49.1 %) experienced at least one COVID-19 event. COVID-19 infection was associated with increased risk of exacerbations (adjusted HR (aHR) 1.64, 95% CI 1.62 to 1.66) and mortality (aHR 2.25, 95&#x2009;% CI 2.19 to 2.31). Risk rose progressively with repeated infections, reaching an aHR of 2.41 for exacerbations and 2.93 for mortality after three or more events. Long covid was more frequent in patients with multiple infections, but most cases occurred after the first event, with diminishing occurrence after subsequent infections.<br><br>CONCLUSION: Recurrent COVID-19 infections in patients with COPD were linked to progressively higher risk of exacerbations and mortality, whereas the burden of long covid was greatest after the first infection. Preventing the initial infection and reducing reinfection risk remain critical components of COPD care in the post-COVID-19 era.},
}
@article {pmid41650882,
year = {2026},
author = {Engert, LC and Dang, R and Daniel, S and Bertisch, SM and Maley, JH and Fong, TG and Serhan, CN and Mullington, JM and Haack, M},
title = {Sleep disturbance affects inflammatory resolution in Long COVID.},
journal = {Prostaglandins, leukotrienes, and essential fatty acids},
volume = {208},
number = {},
pages = {102728},
pmid = {41650882},
issn = {1532-2823},
support = {R35 GM139430/GM/NIGMS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; R21 NS128815/NS/NINDS NIH HHS/United States ; M01 RR001032/RR/NCRR NIH HHS/United States ; S10 OD032292/OD/NIH HHS/United States ; S10 RR027926/RR/NCRR NIH HHS/United States ; },
abstract = {BACKGROUND: Sleep disturbance, which is a common symptom in Long COVID, promotes a pro-inflammatory state and dysregulates lipid-derived specialized pro-resolving mediators (SPMs), presumably contributing to chronic unresolved inflammation. This study aimed to investigate the role of sleep disturbance in inflammatory resolution in Long COVID.<br><br>METHODS: We studied 39 participants (30F/9M, age range 22-68 years), including 31 individuals with Long COVID and 8 SARS-CoV-2-infected controls, who did not develop Long COVID. The study consisted of a 14-day at-home phase followed by a 1-day (24-h) in-laboratory stay. Sleep disturbance was assessed using PROMIS Sleep Disturbance T-scores. During the in-laboratory stay, a fasting morning blood sample was taken for assessment of lipid mediators. Data were analyzed using generalized linear mixed models.<br><br>RESULTS: Participants with Long COVID reported higher sleep disturbance than controls (p<.001). Pro-inflammatory lipid pathways were upregulated in Long COVID compared to control, as indicated by higher prostaglandin E2 (PGE2) levels (p<.05). Long COVID participants with high sleep disturbance (PROMIS Sleep Disturbance T-score &#x2265;60) had lower SPM levels, including the precursor of D-series resolvins 17-hydroxydocosahexaenoic acid (17-HDHA), 17R/S-resolvin D1 (17R/S-RvD1), 15R-lipoxin B4 (15R-LXB4), and protectin D1n-3 DPA (PD1n-3 DPA) than those with low sleep disturbance (T-score <60) (p<.05).<br><br>CONCLUSIONS: This study suggests that sleep disturbance may contribute to chronic inflammation in Long COVID by compromising certain inflammatory resolution pathways. Promoting inflammatory resolution physiology in particular in those individuals with Long COVID suffering from sleep disturbance may serve as a mechanistic target to mitigate inflammation and symptom burden in Long COVID.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT05606211.},
}
@article {pmid41650532,
year = {2026},
author = {Labied, S and Atifi, F and Wahnou, H and Mabrouk, M and Jeddoub, O and Allaoui, A and Jalali, F and Zaid, Y},
title = {Megakaryocytes and afucosylated IgG in post-acute COVID-19: Bridging immune dysregulation and vascular pathology - A narrative review.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {196},
number = {},
pages = {119049},
doi = {10.1016/j.biopha.2026.119049},
pmid = {41650532},
issn = {1950-6007},
abstract = {Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as long COVID, encompasses a constellation of persistent symptoms lasting for at least three months after acute SARS-CoV-2 infection and not explained by alternative diagnoses. The multifactorial pathophysiology underlying PASC remains incompletely understood, limiting the development of effective management strategies. Increasing evidence suggests that both immune dysregulation and hemostatic imbalance play central roles in post-COVID-19 complications. Megakaryocytes, key regulators of platelet production and coagulation, have emerged as potential contributors to sustained thrombo-inflammatory processes following SARS-CoV-2 infection. In parallel, afucosylated IgG antibodies have been strongly implicated in exaggerated immune activation and hyperinflammatory responses during acute COVID-19. The persistence of such antibody glycosylation patterns beyond the acute phase raises the possibility that they may also contribute to chronic immune and vascular alterations observed in PASC. This narrative review explores the potential interplay between megakaryocyte dysfunction and afucosylated IgG antibodies in the pathogenesis of PASC. By examining mechanisms identified during acute SARS-CoV-2 infection, we discuss how prolonged immune-hemostatic crosstalk may promote persistent inflammation, endothelial dysfunction, and microvascular abnormalities. Understanding these interconnected pathways may provide mechanistic insight into the heterogeneity of PASC manifestations and help identify novel therapeutic targets for long-term post-COVID-19 sequelae.},
}
@article {pmid41649660,
year = {2026},
author = {Hidayana, I and Rahvenia, Z and Pelupessy, DC and Ahmad, MU},
title = {Quality of life among individuals with long COVID symptoms in Indonesia at four points of recovery.},
journal = {Discover mental health},
volume = {},
number = {},
pages = {},
doi = {10.1007/s44192-026-00374-y},
pmid = {41649660},
issn = {2731-4383},
}
@article {pmid41649074,
year = {2026},
author = {Busnel, Y and Légaré, F and Moumjid, N and Panse, L and Testud, A and Tran, VT and Haesebaert, J},
title = {Shared Decision Making among Patients with Chronic Conditions in France: A Cross-Sectional Survey in the ComPaRe E-Cohort.},
journal = {Medical decision making : an international journal of the Society for Medical Decision Making},
volume = {},
number = {},
pages = {272989X251407617},
doi = {10.1177/0272989X251407617},
pmid = {41649074},
issn = {1552-681X},
abstract = {BackgroundShared decision making (SDM) is a cornerstone of patient-centered care; however, little information is available on how SDM is practiced in routine care. We aimed to assess the level of SDM perceived by patients with chronic conditions for the most important health decision in the past 12 mo.MethodsThis was a cross-sectional online survey among ComPaRe, a nationwide e-cohort of patients with chronic conditions in France. The survey asked participants about their perception of SDM using the 9-item Shared Decision-Making Questionnaire (SDM-Q-9) regarding their most important health decision in the past 12 mo. We weighted the sample to represent French patients with chronic conditions and conducted regression models to identify factors associated with higher SDM levels, adjusting for sociodemographic and clinical characteristics.ResultsIn total, 2,087 patients were analyzed (participation rate: 34.9%). In the weighted sample, 53.0% were women, the mean (SD) age was 51.0 (15) y, and the most frequent conditions were endometriosis (27.3%), inflammatory rheumatic diseases (20.7%), and high blood pressure (19.3%). The most important health decisions in the past 12 mo were mainly about drug treatments (36.5%) or surgery (20.5%). The mean (SD) SDM-Q-9 score was 63 (27)/100 (moderate level of SDM). The highest scores were observed for cancer (70 [26]) and depression (69 [26]), whereas the lowest scores were for long COVID (54 [28]) and endometriosis (58 [25]). Decisions about surgery (71 [25]) and with specialists (64 [27]) were associated with higher scores compared with medication decisions (60 [28]) or with general practitioners (62 [27]). Multivariate analysis confirmed that a higher SDM level was associated with being a man; having higher health literacy; making decisions relating to cancer, surgery, or medical devices; and specialist involvement.ConclusionsPatients with chronic conditions in France report moderate levels of SDM, with substantial variations by condition, decision type, and patient characteristics. Findings highlight the need for tailored strategies to foster SDM in chronic care.HighlightsShared decision making (SDM) is considered a key component of the chronic disease management model.This study provides the first nationwide assessment of perceived SDM levels among patients with chronic conditions in France.Patients have a moderate overall SDM score, but significant disparities exist. Patients with less recognized conditions such as long COVID or endometriosis, low health literacy, and high treatment burden reported significantly lower SDM scores as compared with others in their care decisions.These findings underscore the need for targeted interventions to improve SDM implementation.},
}
@article {pmid41646734,
year = {2026},
author = {Pradeep, A and Carvour, ML and Sivamurugan, SM and Singh, U and Comellas, AP and Dayal, S},
title = {Cardiovascular, renal and pulmonary risks of Long COVID: a retrospective cohort study stratified by age and sex.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.14.26344156},
pmid = {41646734},
abstract = {BACKGROUND: A substantial proportion of patients with acute COVID-19 develop post-acute sequelae of SARS-CoV-2 infection (Long COVID). The risk of adverse cardiovascular and related outcomes in Long COVID remain elusive. We hypothesized that individuals with Long COVID are at elevated risk for adverse cardiovascular, renal and pulmonary (CRP) outcomes compared to those who recovered from COVID-19 without developing Long COVID.<br><br>METHODS: We performed a retrospective cohort study using the global TriNetX electronic health record network (> 150 million patients). Adults with documented COVID-19 were classified by the presence/absence of Long COVID. We analyzed absolute risks (AR) and relative risks (RR) for 15 CRP outcomes, stratified by age (18-50, 51-64, &#x2265;65 years). After excluding those with the preexisting outcomes of interest, propensity score matching was applied to adjust for age, sex, and common confounders.<br><br>RESULTS: Among 2,613,432 adults with COVID-19, 315,612 matched individuals were included in the study. Long COVID was associated with increased AR for most CRP outcomes across adult ages regardless of sex. RR were disproportionately higher in younger adults, especially in females for cardiovascular and renal outcomes and in males for selected pulmonary outcomes. In a secondary analysis among individuals with Long COVID, prior COVID-19 vaccination was not associated with a significantly lower risk of CRP outcomes.<br><br>CONCLUSIONS: Long COVID is associated with increased risk of adverse CRP outcomes, with relatively higher risks observed in younger adults. These findings support the need for continuing surveillance and risk-reduction strategies for cardiovascular and related disorders in Long COVID.},
}
@article {pmid41646510,
year = {2026},
author = {Melo-Oliveira, MES and Lourenço, RA and Louzada, EB and Moutinho, M and Barbosa, AF and Moreira, VG and Porto, LC},
title = {Systematic Review of Dyspnea and Chronic Fatigue in Patients With Long COVID: Clinical Characteristics and Associated Laboratory Parameters.},
journal = {Pulmonary medicine},
volume = {2026},
number = {},
pages = {5426125},
pmid = {41646510},
issn = {2090-1844},
mesh = {Humans ; *Dyspnea/etiology/physiopathology/virology/epidemiology ; *COVID-19/complications/physiopathology ; Quality of Life ; *Fatigue/etiology/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/etiology ; },
abstract = {ABSTRACT: Dyspnea and chronic fatigue stand out as prevalent manifestations in the postacute phase of COVID, resulting in substantial adverse effects on patients' quality of life and functional capacity. Although these symptoms have been widely documented, there is no clear consensus on the pathophysiological mechanisms that underlie them. The available literature reveals a dispersion of clinical and laboratory data, and the variability in the methods of assessment of fatigue and dyspnea, as well as in the laboratory variables examined, limits the standardized understanding of this complex condition.<br><br>OBJECTIVE: This study was aimed at identifying and synthesizing the evidence on the main clinical and laboratory characteristics related to dyspnea and fatigue in patients during long COVID from 2021 onwards.<br><br>METHODS: The main databases used to select the studies were PubMed and Medline, also using LitCovid and Embase.<br><br>RESULTS: A total of 42 articles that met the inclusion criteria were included, covering a total population of 30,682 patients diagnosed with COVID-19. The findings underscore the significant impact of long COVID on patients' quality of life, with persistent symptoms such as fatigue and dyspnea affecting a considerable proportion of individuals for durations ranging from 1 to 24 months.<br><br>CONCLUSION: The heterogeneity in research approaches highlights the urgent need for collaborative initiatives to elucidate the determinants of long COVID symptomatology and create more consistent evaluation protocols.},
}
@article {pmid41645987,
year = {2026},
author = {Vyas, P and Joshi, D and Kanabar, K and Parmar, M and Vadodariya, J and Patel, K and Patel, B and Dave, S and Patel, M and Modi, G},
title = {Incidence and predictors of long Covid-19 in hospitalized patients: A cohort study.},
journal = {The National medical journal of India},
volume = {39},
number = {1},
pages = {19-22},
doi = {10.25259/NMJI_222_2023},
pmid = {41645987},
issn = {2583-150X},
mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Male ; Female ; Incidence ; Middle Aged ; *Hospitalization/statistics &amp; numerical data ; Adult ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; Body Mass Index ; Prospective Studies ; India/epidemiology ; Risk Factors ; Age Factors ; Fatigue/epidemiology ; },
abstract = {Background Long-term Covid-19 symptoms have the potential to negatively impact health and quality of life. We evaluated the incidence and predictors of long Covid-19 among hospitalized patients. Methods We prospectively collected clinical data of 393 patients diagnosed as Covid-19 positive and admitted to our hospital. At 1-year follow-up, all vital parameters and laboratory investigations were recorded. A multiple logistic regression model was used to determine predictors of long Covid-19. Results Long Covid-19 was found in 34.4% of patients at 1-year follow-up. Most commonly reported symptoms were joint pain (40%), fatigue (33%), and dyspnoea (22.9%). Severity of disease at the time of admission (1.5; 95% Confidence Interval [CI] 1.09-2.2; p=0.01), high body-mass index (BMI) (1.1; 95% CI 1.03-1.13; p=0.003) and increased age (1.02; 95% CI 1.00-1.04; p=0.02) were independent predictors of long Covid-19 on follow-up. Conclusion Almost one-third of patients were diagnosed with long Covid-19 at 1-year follow-up. Severity of disease at the time of admission, increased BMI, and increased age were independent predictors of long Covid-19.},
}
@article {pmid41645148,
year = {2026},
author = {Polovin, T and Bilenko, N and Frankenthal, D and Bromberg, M and Keinan-Boker, L and Davidovitch, N},
title = {The association between Post-COVID syndrome and self-stigma among the adult Israeli population during the COVID-19 pandemic.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-026-26489-z},
pmid = {41645148},
issn = {1471-2458},
}
@article {pmid41642863,
year = {2026},
author = {McMillan, M and Beazley, R and Vasilunas, N and Sullivan, TR and Edmond, T and Battersby, A and Britton, PN and McMullan, B and Jureidini, J and Del Fante, S and Marshall, HS},
title = {Children and adolescents: Respiratory infection and long-term effects longitudinal study (CARE Study): Study protocol.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0341566},
pmid = {41642863},
issn = {1932-6203},
mesh = {Humans ; Child ; Adolescent ; *COVID-19/complications/epidemiology/virology ; Longitudinal Studies ; Child, Preschool ; SARS-CoV-2/isolation &amp; purification ; Infant ; *Influenza, Human/complications/epidemiology ; Female ; Male ; *Respiratory Tract Infections/epidemiology ; Australia/epidemiology ; Post-Acute COVID-19 Syndrome ; Infant, Newborn ; Incidence ; },
abstract = {BACKGROUND: The effects of SARS-Cov-2 infection can extend beyond the acute phase of the illness, often described as Long COVID, post-COVID condition (PCC) or Post-acute sequelae of COVID (PASC). Post-acute sequelae (PAS) are also likely to be a problem for a small proportion of children and adolescents following influenza infection. However, there is no comprehensive ongoing data collection in Australian children and adolescents, and global data on both PCC during the SARS-Cov-2 Omicron variant period and PAS following influenza is limited.<br><br>AIM: This study aims to determine the cumulative incidence of PCC in Australian children and adolescents five years after the start of the COVID-19 pandemic. Secondary aims include identifying the cumulative incidence of PAS in children and adolescents following influenza infection.<br><br>METHODS: This longitudinal cohort study will recruit children and adolescents aged 0-18 years in South Australia who tested positive for SARS-Cov-2 or influenza in the previous 2 months. Following consent, participants will complete an online baseline survey and then at 3, 6, and 12 months post-infection. The survey has been adapted from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Paediatric COVID-19 follow-up survey. The survey includes validated assessment tools such as the Pediatric Quality of Life Inventory (PedsQL), Multidimensional Fatigue Scale, and the Malm&#xf6; Postural Orthostatic Tachycardia Syndrome (POTS) Score questionnaire. PCC following COVID-19 and PAS following influenza infection will be identified according to an adapted World Health Organization definition of PCC in children and adolescents.<br><br>DISCUSSION: This study addresses gaps in understanding PCC and PAS following influenza in children and adolescents during Omicron circulation. Whilst it is no longer feasible to prospectively compare post-acute sequelae in children and adolescents who have never had COVID-19, this design allows a comparison with another common viral infection, influenza, informing clinical management of children post-infection.},
}
@article {pmid41642857,
year = {2026},
author = {Churiwal, M and Tompkins, K and Streeter, G and Litel, C and Mason, S and Lin, K and Muller, M and Chhetri, S and Belvin, T and Lin, FC and Basham, C and Whittelsey, M and Rapp, T and Premkumar, L and Cerami, C and Lin, JT},
title = {Symptom burden, viral load, and antibody response to ancestral SARS-CoV-2 strain [D614G] in an outpatient household cohort.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0313467},
pmid = {41642857},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/virology/immunology/epidemiology ; *Viral Load ; Male ; *SARS-CoV-2/immunology/genetics/isolation &amp; purification ; Female ; Middle Aged ; Adult ; *Antibodies, Viral/blood/immunology ; Outpatients ; Aged ; Cohort Studies ; Antibody Formation ; Family Characteristics ; Young Adult ; Symptom Burden ; },
abstract = {BACKGROUND: Early in the SARS-CoV-2 pandemic, description of COVID-19 illness among non-hospitalized patients was limited. Data from household cohorts can help reveal the full spectrum of disease and the potential for long-term sequelae, even in non-severe disease.<br><br>METHODS: Daily symptom diaries were collected in a US household cohort of SARS-CoV-2 infection from April to November 2020, during the pre-COVID vaccine period. SARS-CoV-2 nasal viral loads were measured at study entry and weekly until day 21; serologic testing was performed at study entry and day 28. A subset of volunteers underwent an additional assessment 8-10 months later. Participants who met the criteria for early infection-testing antibody-negative at study entry but PCR-positive either at baseline or during follow-up-were included in this analysis (n&#x2009;=&#x2009;143).<br><br>RESULTS: Daily symptoms were ascertained in 143 outpatients with acute COVID-19, including 60 index cases who sought testing and 83 of their household contacts. Asymptomatic cases comprised 16% (13/83) of SARS-CoV-2 infections detected among household contacts. Among 119 persons with mild or moderate illness, the number of symptoms peaked 3 or 4 days after symptom onset. Fever and anosmia occurred in nearly half of participants. Symptom severity was associated with increased age, viral load, and cardiovascular disease. Increased BMI was associated with a higher antibody level at day 28, independent of symptom severity. Those with a higher day 28 antibody level were more likely to develop symptoms consistent with post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID-19, 8-10 months later.<br><br>CONCLUSIONS: Fever, anosmia, as well as asymptomatic infection were common features of COVID-19 non-severe illness when the D614G variant circulated in the US, before the availability of vaccines or outpatient therapies. Antibody levels following acute infection were linked to the development of symptoms of PASC 8-10 months later.},
}
@article {pmid41641915,
year = {2026},
author = {Hilbert, T and MacEachern, SN and Zhang, Y},
title = {Robust Distribution-Free Tests for the Linear Model.},
journal = {Statistics in medicine},
volume = {45},
number = {3-5},
pages = {e70404},
pmid = {41641915},
issn = {1097-0258},
support = {SES-1921523//National Science Foundation/ ; DMS-2413823//National Science Foundation/ ; DMS-2311109//National Science Foundation/ ; },
mesh = {Humans ; Linear Models ; COVID-19/immunology ; Computer Simulation ; Data Interpretation, Statistical ; },
abstract = {Recently, there has been growing concern about heavy-tailed and skewed noise in biological data. We introduce RobustPALMRT, a flexible permutation framework for testing the association of a covariate of interest adjusted for control covariates. RobustPALMRT controls type I error rate for finite-samples, even in the presence of heavy-tailed or skewed noise. The new framework expands the scope of state-of-the-art tests in three directions. First, our method applies to robust and quantile regressions, even with the necessary hyper-parameter tuning. Second, by separating model-fitting and model-evaluation, we discover that performance improves when using a robust loss function in the model-evaluation step, regardless of how the model is fit. Third, we allow fitting multiple models to detect specialized features of interest in a distribution. To demonstrate this, we introduce DispersionPALMRT, which tests for differences in dispersion between treatment and control groups. We establish theoretical guarantees, identify settings where our method has greater power than existing methods, and analyze existing immunological data on Long-COVID patients. Using RobustPALMRT, we unveil novel differences between Long-COVID patients and others even in the presence of highly skewed noise.},
}
@article {pmid41641052,
year = {2025},
author = {Li, G and Zhao, Y and Gu, W and Wang, Q and Lu, X and Miao, X},
title = {The problem of frailty caused by acute infection and future health management strategies to improve frailty.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1735577},
pmid = {41641052},
issn = {2296-2565},
mesh = {Humans ; Female ; *Frailty/epidemiology/etiology ; Male ; Aged ; *COVID-19/epidemiology ; China/epidemiology ; Middle Aged ; Follow-Up Studies ; Adult ; SARS-CoV-2 ; Aged, 80 and over ; Frail Elderly/statistics &amp; numerical data ; Proportional Hazards Models ; Interrupted Time Series Analysis ; },
abstract = {BACKGROUND: We aimed to analyze changes in frailty associated with long-COVID, while providing effective health management measures to improve frailty.<br><br>METHODS: We conducted a 4-month follow-up cohort study involving 2,471 participants to analyze changes in body frailty after the prevalence of COVID-19 in China. We performed interrupted time series analysis to estimate the impact of acute infection on the changes in frailty. The time-dependent COX model was considered to assess the association between frailty status and infection, and sensitivity analysis was performed to verify the stability of the results. In addition, we established a traditional Cox model to analyze the relationship between healthy behaviors and infections, aiming to improve health management and reduce frailty.<br><br>RESULTS: There were significantly elevated trend changes in the frailty index compared to the prepandemic period in the total population (+0.029[0.016, 0.041], p&#x202f;<&#x202f;0.001), and the frailty index was found to be higher in female individuals and people aged over 65&#x202f;years. Participants with moderate frailty (HR&#x202f;=&#x202f;1.19, 95% CI: 1.04-1.35, p&#x202f;<&#x202f;0.001) and severe frailty (HR&#x202f;=&#x202f;1.34, 95%CI: 1.15-1.56, p&#x202f;<&#x202f;0.001) had a significantly higher hazard of infection than those with mild frailty. Long-term health monitoring indicated that positive mood, appropriate physical activities, sufficient intake of grains and vegetables, and reduced intake of sugary drinks can improve frailty and ultimately reduce the risk of infection.<br><br>CONCLUSION: In this study, it was found that the population generally became more frail after the pandemic, and frailty increases the risk of acute reinfection. Therefore, it is necessary to carry out health management strategies to improve frailty.},
}
@article {pmid41641003,
year = {2025},
author = {Leclerc, L and Poudrier, J and Power, C and Lam, GY and Falcone, EL},
title = {Intestinal barrier compromise, viral persistence, and immune dysregulation converge on neurological sequelae in Long COVID.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1744415},
pmid = {41641003},
issn = {1663-4365},
abstract = {Long COVID (LC) is a multisystem, post-infectious conditions diagnosed ≥3 months after acute SARS-CoV-2 infection and marked by relapsing, persistent, or progressive symptoms, especially fatigue, post-exertional symptom exacerbation and neuropsychiatric syndromes. We synthesized evidence suggesting that LC arises from intersecting pathways including viral persistence, intestinal dysbiosis and barrier compromise with microbial translocation, innate immune activation with neutrophil extracellular traps (NET) and thromboinflammation, and immune dysregulation with features of exhaustion and autoimmunity. These processes adversely impact blood-brain barrier (BBB) function and lead to neuroinflammation. We propose a mechanistic model in which viral antigens and translocated microbial products amplify pro-inflammatory networks promoting immunothrombosis and tissue hypoperfusion. Hematogenous and gut-brain pathways may then deliver inflammatory mediators to the central nervous system (CNS), resulting in BBB disruption and glial activation that underpin nervous system disorders in LC. Treatment regimens aimed at lowering antigen load, restoring mucosal barrier integrity and modulating myeloid/coagulation pathways may warrant investigation as novel therapeutic strategies to treat LC.},
}
@article {pmid41639776,
year = {2026},
author = {Aboulwafa, A and Lebbe, A and Khalil, A and Bayraktar, N and Mushannen, B and Ayoub, S and Sarker, S and Abdalla, MN and Laws, S and Mohammed, I and Yagan, L and Mushannen, M and Zakaria, D},
title = {New onset of severe and long-term hepatobiliary diseases post-COVID-19 infection: a systematic review.},
journal = {BMC infectious diseases},
volume = {26},
number = {1},
pages = {253},
pmid = {41639776},
issn = {1471-2334},
abstract = {BACKGROUND: The COVID-19 pandemic has resulted in a surge of reports linking the virus to various systemic complications, including hepatobiliary disorders. Understanding the spectrum and severity of hepatobiliary diseases following COVID-19 infection is crucial for comprehensive patient management and long-term health outcomes.<br><br>METHODS: A systematic review was conducted to identify studies reporting on hepatobiliary manifestations post-COVID-19 infection. PubMed, Medline, Embase, Scopus, Web of Science, Science Direct and Cochrane Library databases were searched in October 2023, with set inclusion and exclusion criteria in place to select papers documenting new onset hepatobiliary diseases following COVID-19 infection.<br><br>RESULTS: A total of 23 studies met the inclusion criteria, covering a diverse range of hepatobiliary conditions such as acute hepatitis, cholestasis, autoimmune liver diseases, and gallbladder pathology.<br><br>CONCLUSION: This systematic review underscores the emerging evidence of severe and long-term hepatobiliary diseases following COVID-19 infection. Healthcare providers should maintain a high index of suspicion for hepatobiliary complications in patients recovering from COVID-19, emphasizing the need for prolonged monitoring and specialized management strategies to mitigate long-term morbidity and mortality."<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-11840-3.},
}
@article {pmid41639746,
year = {2026},
author = {Guo, P and Lim, JT and Wee, LE and Tay, AT and Zhai, Y and Chiew, CJ and Ong, B and Lye, DCB and Tan, KB},
title = {Characterization of post-acute multi-organ sequelae following SARS-CoV-2 Infection in the Delta and Omicron Eras in a highly boosted population.},
journal = {BMC global and public health},
volume = {4},
number = {1},
pages = {15},
pmid = {41639746},
issn = {2731-913X},
abstract = {BACKGROUND: Multi-organ post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is extensively documented. Recent studies in predominantly Caucasian populations suggest that the evolution of SARS-CoV-2 variants can influence risk (as measured by hazard ratios) and rates (as measured by incidence rate ratios) of PASC, and they also highlight the protective effects of COVID-19 vaccination. However, it is unclear whether risks or rates of PASC have changed over different Omicron subvariants in an Asian population with high uptake of COVID-19 vaccine booster doses.<br><br>METHODS: We constructed a national cohort of individuals infected with SARS-CoV-2 and estimated the 31-300-day risks and rates of pre-specified new-incident diagnoses across the cardiovascular, neuropsychiatric, auto-immune, renal, and gastrointestinal domains between 1,427,985 and 3,284,081 unique individuals who tested positive or negative for SARS-CoV-2 infection respectively, across Delta, Omicron BA.1/2, BA.4/5, and XBB predominance. We compared risks/rates of new-incident diagnoses between test positives and test negatives in each era.<br><br>RESULTS: Compared to test-negatives, asides from increased risk of renal outcomes in BA.1/2 (aHR, 1.17; 95% CI, 1.09-1.26), there were no increased risks of composite diagnoses in other organ systems across all 4 variants of concern. In terms of individual outcomes, there were increased risks or rates of diagnosis of individual neuropsychiatric outcomes, such as memory problems, Alzheimer's disease across all eras, and loss of smell or taste only in Delta. There were also increased risks of diagnosis of individual renal outcomes, such as end stage renal failure in BA.1/2 (aHR, 1.52; 95% CI, 1.27-1.81). In COVID-19 survivors who were hospitalised, risks and rates of cardiovascular, neuropsychiatric, and renal diagnoses in the post-acute period were increased in most eras. COVID-19 vaccinations reduced the risks of composite diagnoses.<br><br>CONCLUSIONS: The risks/rates of pre-specified new-incident multi-organ PASC were modest over all studied COVID-19 eras. The risk was further attenuated with booster vaccination during the Omicron BA.4/5 and XBB periods compared with the Omicron BA.1/2 period.},
}
@article {pmid41638903,
year = {2026},
author = {Sarkar, BK and Kumar, A},
title = {The role of artificial intelligence in managing COVID-19 and long COVID: a narrative review.},
journal = {Osong public health and research perspectives},
volume = {},
number = {},
pages = {},
doi = {10.24171/j.phrp.2025.0347},
pmid = {41638903},
issn = {2210-9099},
abstract = {The coronavirus disease 2019 (COVID-19) pandemic had an unprecedented global impact, resulting in both positive and negative consequences. The virus not only affected millions of lives worldwide but also caused long-term harm to multiple organ systems in many survivors, thereby substantially impairing quality of life. This persistent condition is now referred to as long COVID (LC). The aim of this study is to raise awareness of LC-related organ system impacts and to highlight the key role of artificial intelligence (AI) in mitigating these effects. The present research conducts a narrative review focusing on LC-related impacts. In this context, unstructured searches were conducted to identify a total of 69 relevant studies indexed in Embase, PubMed, Web of Science, or Scopus, each of which was reviewed by at least 2 experts with sufficient domain knowledge in health sciences. Based on the authors' perspectives and insights, the review narratively examines damage to human organ systems attributable to LC and explores the role of AI in addressing LC-related challenges. Significant ethical, practical, and societal concerns arising from the extensive use of AI, particularly major issues such as data privacy and algorithmic bias, are also discussed. LC has caused lasting impacts on human organ systems, while AI is offering substantial potential for LC-related care.},
}
@article {pmid41636553,
year = {2026},
author = {Shi, F and Xia, H and Li, X and Olatosi, B and Weissman, S and Yang, X},
title = {Long COVID Between People With and Without HIV: a Statewide Cohort Analysis.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAI.0000000000003840},
pmid = {41636553},
issn = {1944-7884},
abstract = {BACKGROUND: This study aims to compare the risks of a panel of long COVID manifestations between people with HIV (PWH) and people without HIV (PWoH).<br><br>METHODS: Using integrated statewide electronic health record data from the HIV cohort and COVID-19 tester cohort, we identified COVID-19-positive individuals by HIV status between March 02, 2020, and January 15, 2022, in South Carolina. A total of 13 diagnosis groups encompassing 131 potential long COVID categories were identified. We used inverse probability weighting based on propensity scores to balance covariates between the PWH and PWoH, including age, sex, race, and vaccination status. Cox Proportional Hazard regression models were used to estimate the risk of each diagnosis group examined.<br><br>RESULTS: Among a total of 838,520 COVID-19 positive individuals, 2,662 were with HIV, and 835,858 were without HIV. The prevalence of any long COVID diagnosis was 16.3% and 10.6% for PWH and PWoH, respectively. Compared with PWoH, PWH were found to be at a higher risk of at least one of the long COVID diagnosis groups (HR = 1.29, 95%CI: 1.09-1.54) and the highest risk was for diseases of the nervous system (HR = 2.04, 95%CI: 1.42-2.92), followed by mental disorders (HR = 1.78, 95%CI: 1.12-2.82) and respiratory system (HR = 1.78, 95%CI: 1.18-2.69).<br><br>CONCLUSIONS: Our study highlights the consistent and elevated LC burden in PWH, emphasizing the importance of sustained follow-up for COVID-19 survivors to improve their clinical outcomes and prevent morbidity of LC.},
}
@article {pmid41635577,
year = {2026},
author = {Khoo, A and Manuel, K and Ng, T and Crotty, M},
title = {Non-invasive electrodiagnostic testing for small fibre neuropathy in long COVID-19.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001399},
pmid = {41635577},
issn = {2632-6140},
abstract = {BACKGROUND: Long COVID-19 is associated with a diverse range of debilitating neuropathic and autonomic symptoms that may indicate small fibre neuropathy (SFN). We aimed to assess the utility of multimodal non-invasive electrodiagnostic techniques in evaluating symptomatic individuals.<br><br>METHODS: People with confirmed long COVID-19 who scored >10 points on the Small Fibre Neuropathy Screening List (SFNSL) questionnaire underwent routine neurophysiological testing and a non-invasive SFN protocol of (a) sympathetic skin responses, (b) cutaneous silent period, (c) quantitative thermal thresholds and (d) electrochemical skin conductance. Clinical and demographic information was collected on all individuals who underwent comprehensive physical and psychometric evaluation, including a 6-min walk test, National Aeronautics and Space Administration (NASA) Lean Test, Composite Autonomic Symptom Score-31 (COMPASS-31), European Quality of Life 5-Dimension 5-Level Questionnaire (ED-5D-5L), Modified Fatigue Impact Scale (MFIS) score and Patient Health (depression) Questionnaire (PHQ-9).<br><br>RESULTS: We assessed nine individuals, of whom three (33%) had neurophysiological evidence of SFN. Median age was 47.8 (range 26.3-67.6) years, duration from COVID-19 infection 23.0 (range 8.5-35.7) months and median SFNSL 34/84. All individuals scored highly in disability measures.<br><br>CONCLUSIONS: Long COVID-19 is associated with functional disability and reduced quality of life. SFN should be considered in all individuals with a suggestive clinical phenotype of neuropathic and autonomic symptoms.},
}
@article {pmid41633328,
year = {2026},
author = {Kwon, K and Jang, CY and Kim, W and Son, J and Chang, E and Kim, SH},
title = {Evaluation of Post-Acute Sequelae of SARS-CoV-2 (PASC) Index and a Recent Long COVID Criteria in Korean Long COVID-19 Cohort.},
journal = {Journal of Korean medical science},
volume = {41},
number = {5},
pages = {e54},
pmid = {41633328},
issn = {1598-6357},
support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; },
mesh = {Humans ; *COVID-19/complications/epidemiology/diagnosis ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Aged ; SARS-CoV-2 ; Republic of Korea/epidemiology ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; },
abstract = {BACKGROUND: To compare the post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC) index and the National Academies of Sciences, Engineering, and Medicine (NASEM) criteria in identifying long coronavirus disease (COVID) among adults with confirmed coronavirus disease 2019.<br><br>METHODS: A prospective cohort study was conducted from November 2022 to February 2025 at a single tertiary care hospital in Seoul, Korea. Adults aged 18 years or older with confirmed SARS-CoV-2 infection were enrolled, yielding a total of 183 participants. Follow-up assessments took place at 1-, 3-, 6-, and 12-months post-infection. The primary outcome was the prevalence of long COVID at 12 months, measured using the PASC index (&#x2265; 12 points across specified symptoms) and the NASEM criteria (&#x2265; 1 symptom persisting for at least 3 months).<br><br>RESULTS: Of 183 participants, 26.2% (48/183) met the PASC index, whereas 47.5% (87/183) fulfilled the NASEM criteria. Of the 48 patients who met the PASC index, 44 (91.7%) also met the NASEM criteria.<br><br>CONCLUSION: The NASEM criteria classified nearly half of participants with long COVID and covered those with PASC index, while the PASC index identified about one quarter. Although the NASEM criteria capture a broader range of persistent symptoms, the PASC index may offer a more stringent threshold, potentially informing targeted research and clinical decision-making.},
}
@article {pmid41632491,
year = {2026},
author = {Nóbrega Júnior, JC and Brandão, SS and Fink, JB and Xavier, D and Torres, R and Ari, A and Reinaux, C and Campos, S and Brandão, D and Dornelas de Andrade, A},
title = {Effect of Inspiratory Muscle Training on Aerosol Deposition and Pulmonary Perfusion in Post-COVID-19 Syndrome: A Gamma Scintigraphy Study.},
journal = {Journal of aerosol medicine and pulmonary drug delivery},
volume = {},
number = {},
pages = {19412711261418482},
doi = {10.1177/19412711261418482},
pmid = {41632491},
issn = {1941-2703},
abstract = {BACKGROUND: Pulmonary dysfunction in individuals with post-coronavirus disease-2019 (COVID-19) syndrome may impair aerosol deposition and pulmonary perfusion, compromising respiratory efficiency. Inspiratory muscle training (IMT) has been proposed as a strategy to improve respiratory mechanics and lung function.<br><br>OBJECTIVE: To compare aerosol deposition and pulmonary perfusion in individuals with post-COVID-19 syndrome before and after 8 weeks of IMT.<br><br>METHODS: This was a randomized controlled clinical trial involving 19 participants, divided into an IMT group (n = 10) and a control group (n = 9). The IMT group performed training with a load adjusted to 50% of maximal inspiratory pressure, while the control group used a device without resistance. Aerosol deposition and pulmonary perfusion were evaluated by gamma scintigraphy using the radioisotopes technetium-labeled diethylene-triamine-pentaacetic acid and technetium99-labeled macroaggregated human serum albumin, respectively. Total radiopharmaceutical activity in both lungs, as well as in the right and left lungs separately, was quantified pre- and post-intervention.<br><br>RESULTS: After 8 weeks, the IMT group showed a significant increase in total lung activity for both aerosol deposition (p = 0.028) and perfusion (p = 0.013). In the right lung, activity increased significantly for aerosol deposition (p = 0.005) and perfusion (p = 0.005). In the left lung, significant increases were also observed for perfusion (p = 0.007). No significant increases were observed in the control group. In the between-group analysis, the IMT group showed higher activity in both lungs combined and separately, compared with controls, for aerosol deposition (all p < 0.05) and in the right lung for perfusion (p = 0.010).<br><br>CONCLUSION: IMT improved total aerosol deposition and perfusion in individuals with post-COVID-19 syndrome. These findings support the use of IMT as a rehabilitation strategy to enhance pulmonary deposition of inhaled agents and increase pulmonary perfusion in this population.},
}
@article {pmid41630820,
year = {2026},
author = {Rivas Nieto, JC and Cordoba-Melo, BD and Arango-Ibanez, JP and Seni-Molina, S and Barbosa Rengifo, MM and Miranda-Bastidas, CA and Casanova Rojas, AF and Mina Sanchez, AF and Herrera, CJ and Quintana Da Silva, MA and Buitrago, AF and Coronel Gilio, ML and Pow-Chon-Long, F and Gomez-Mesa, JE and , },
title = {Long-Term Mental Health Evaluation After COVID-19: Insights From the CARDIO COVID 20-21 Registry.},
journal = {Journal of clinical medicine research},
volume = {18},
number = {1},
pages = {18-30},
pmid = {41630820},
issn = {1918-3003},
abstract = {BACKGROUND: Psychopathological manifestations are key features of long COVID, contributing to a considerable global mental health burden. Neuropsychiatric sequelae such as anxiety, depression, cognitive dysfunction, and perceived stress may persist for months or years after infection. Latin American populations remain underrepresented, despite a high prevalence of long COVID and unique socio-demographic characteristics. Understanding these impacts is essential for targeted screening and interventions.<br><br>METHODS: We conducted a prospective study of patients hospitalized for severe COVID-19. Psychiatric evaluation used the General Anxiety Disorder-7, Patient Health Questionnaire-9, Perceived Stress Scale-14, and Addenbrooke's Cognitive Examination-III (ACE-III), at an average of 24.5 months post-illness. Bivariate analyses evaluated differences by sex and intensive care unit (ICU) admission. Multivariable linear regression was used to examine associations between cognitive scores and age, sex, education, socioeconomic status, ICU admission, body mass index, smoking exposure, hypertension, and diabetes.<br><br>RESULTS: We included 152 patients; the mean age was 56 years, and 58.5% were male. Anxiety symptoms were present in 33%, depression in 49%, and both perceived stress and cognitive dysfunction were each observed in 11% of patients. Women exhibited significantly higher levels of depression (P = 0.02) and stress (P = 0.011), whereas patients admitted to the ICU demonstrated greater cognitive impairment (P < 0.001). In multivariable regression, male sex (P = 0.002), higher education (P < 0.001), and hypertension (P = 0.037) were significantly associated with higher ACE-III scores, while ICU admission was associated with lower scores (P = 0.017).<br><br>CONCLUSION: Our study reveals a high prevalence of mental health symptoms and cognitive dysfunction among patients 2 years after severe COVID-19. Anxiety showed no differences by sex or ICU requirement. Women exhibited higher rates of depression and perceived stress, while ICU admission was associated with poorer cognitive performance. Our findings should encourage systematic screening, diagnosis, and management of long-term neuropsychiatric sequelae in COVID-19 survivors. However, due to the limitations of the single-center design, further longitudinal and multicenter studies are warranted to better elucidate the long-term psychiatric impact of COVID-19.},
}
@article {pmid41629267,
year = {2026},
author = {Sanal-Hayes, NE and Hayes, LD and Mair, JL and Iacono, AD and Ingram, J and Mclaughlin, M and Ormerod, J and Carless, D and Hilliard, N and Meach, R and Sculthorpe, NF},
title = {A digital platform with activity tracking for energy management support in long COVID: a randomised controlled trial.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {945},
pmid = {41629267},
issn = {2041-1723},
support = {COV-LT2-0010//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0010//DH | National Institute for Health Research (NIHR)/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/therapy/physiopathology/complications ; Middle Aged ; Adult ; *Mobile Applications ; SARS-CoV-2 ; Aged ; Exercise ; *Fitness Trackers ; Surveys and Questionnaires ; Wearable Electronic Devices ; },
abstract = {In a 6-month pragmatic randomised controlled trial (RCT; ISRCTN16033549), we compared a just-in-time intervention to support energy management in adults with long COVID (LC) to standard care. Participants received either the 'Pace Me' app and a wearable activity tracker (intervention) or an app only with data entry screens (control). The intervention group received just-in-time messages on energy management when they reached 50%, 75%, and 100% of their daily 'activity allowance'. The primary outcome was post-exertional malaise (PEM) measured by the DePaul Symptom Questionnaire-PEM (DSQ-PEM). Of 369 participants assessed for eligibility, 250 participants were randomised 1:1, and 77 controls and 84 intervention participants were included in the final per-protocol analysis. There was no time by group interaction for the DSQ-PEM. The intervention group value was 48 (95% CI 44-53) at baseline and 46 (95% CI 41-51) post-intervention (arbitrary units). The control group value was 47 (95% CI 42-52) at baseline and 44 (95% CI 39-49) at follow-up (interaction effect p = 0.614, η[2]p = 0.002; trivial). No individual question exhibited an interaction effect (p > 0.05). Although the intervention had minimal effect compared to control, the substantial recovery rates previously reported in LC, coupled with our wide inclusion criteria may have masked intervention effects. Therefore, future studies should consider this energy management framework in conditions without such recovery rates, such as CFS.},
}
@article {pmid41628929,
year = {2026},
author = {Bruschi, M and Del Riccio, M and Lorini, C and Profili, F and Zanobini, P and Biagi, C and Papini, E and Floridia, M and Onder, G and Francesconi, P and Bonaccorsi, G},
title = {Prevalence of long covid symptoms in Tuscany, Italy: a population-representative cross-sectional telephone survey.},
journal = {BMJ open},
volume = {16},
number = {2},
pages = {e101321},
pmid = {41628929},
issn = {2044-6055},
mesh = {Humans ; Italy/epidemiology ; Female ; Male ; Cross-Sectional Studies ; *COVID-19/epidemiology/complications ; Middle Aged ; Prevalence ; Adult ; Aged ; SARS-CoV-2 ; Fatigue/epidemiology ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Young Adult ; Telephone ; Adolescent ; },
abstract = {OBJECTIVES: Long covid affects over 36 million individuals in the European region, but its clinical profile is still poorly defined, particularly in the general population with less severe acute disease. This study aimed to assess the prevalence of a broad spectrum of symptoms potentially linked to long covid in the general population of Tuscany, Italy.<br><br>METHODS: A cross-sectional study was conducted in January-February 2024 using Computer-Assisted Telephone Interviews in a representative population sample of Tuscany. Based on the WHO questionnaire long covid symptom list, data on 33 symptoms experienced in the past 6&#x2009;months were collected, along with demographic and clinical characteristics. After excluding patients with COVID-19 within the past 6&#x2009;months and those failing a screening cognitive test, symptom prevalence and ORs adjusted for sex, time since infection, smoking and concurrent diseases (aOR) were calculated according to COVID-19 history.<br><br>RESULTS: After excluding 129 failing the cognitive test (6.4%) and 123 recent COVID cases (6.1%), among 1753 participants interviewed, 1013 (57.8%) had a history of COVID-19. The symptoms significantly more prevalent in individuals with previous COVID-19 were fatigue (12.8% vs 8.9%, aOR 1.6 (95%&#x2009;CI 1.2 to 2.2)), concentration impairment (5.5% vs 2.4%, aOR 2.2 (95%&#x2009;CI 1.3 to 3.8)) and skin rashes (4.5% vs 2.4%, aOR 1.9 (95%&#x2009;CI 1.1 to 3.3)). Prevalences and ORs were higher in more recent COVID-19 cases, particularly females and individuals with concurrent diseases.<br><br>CONCLUSIONS: We identified in a population-based study some symptoms significantly more common in individuals with previous COVID-19. This approach complements data collected in clinical settings and in patients selected by greater disease severity. The findings may help future surveillance efforts and targeted public health interventions directed at optimising care pathways and mitigating long-term consequences.},
}
@article {pmid41627925,
year = {2026},
author = {Tangjitgamol, S and Maude, RR and Ativanichayapong, N and Walsh, R and Beer, E and Kaprakhon, K and Chaowanklang, C},
title = {Prevalence and pattern of abnormal menstruation after COVID-19 infection.},
journal = {Health care for women international},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/07399332.2026.2617332},
pmid = {41627925},
issn = {1096-4665},
abstract = {OBJECTIVE: To evaluate the prevalence of abnormal menstruation after COVID infection as well as the type of abnormality and risk factors.<br><br>METHODS: Data of women who still had menstruation with a history of COVID infection from February 2021 to June 2022 were collected. Clinical features, the presence and pattern of abnormal menstruation post-infection, were obtained through the questionnaire.<br><br>RESULTS: Of 87 women, the mean age was 33.5&#x2009;&#xb1;&#x2009;7.2&#x2009;years. Nine had preexisting menstrual abnormalities (10.3%). The abnormalities were found in 20 women (23.0%), or 2.2-fold higher post-infection. Among these, 17 women (68.0%) had newly developed symptoms. Irregular menstruation was most common in both settings, 33.3% pre-infection and 20.0% post-infection. By univariate analysis, features with higher risk were age &#x2264; 33&#x2009;years (crude odds ratio [cOR] 1.61), obesity (cOR 1.74), COVID vaccination > 3 doses (cOR 3.28), > 1 episode of infection (cOR 3.94), contraception use before (OR 1.47) or after infection (cOR 1.92), abnormal menstruation before COVID infection (cOR 44.0), and presence of other long COVID symptoms (cOR 2.09). The differences were statistically significant for vaccination > 3 doses and had abnormal menstruation pre-infection, with the latter as an independent risk by multivariate analysis (adjusted OR 39.58).<br><br>CONCLUSION: The prevalence of abnormal menstruation post-COVID infection was 23%. Abnormal menstruation pre-infection was an independent risk factor.},
}
@article {pmid41625963,
year = {2026},
author = {Huang, YW and Chen, YC and Lun Lau, EY and Su, YC and Tai, LK and Rosenthal, J and Wang, J and Lee, TY},
title = {REGENECYTE cord blood cell therapy in post-COVID syndrome: a phase IIa randomized, placebo-controlled trial.},
journal = {EClinicalMedicine},
volume = {91},
number = {},
pages = {103737},
pmid = {41625963},
issn = {2589-5370},
abstract = {BACKGROUND: Post-COVID syndrome affects a substantial proportion of individuals worldwide and imposes significant healthcare and economic burdens. Fatigue is one of the most common and debilitating symptoms in those with severe symptoms related to post-COVID fatigue syndrome, yet there remains a lack of targeted therapies, effective or approved treatments to address it. This study aimed to evaluate the safety, tolerability, and efficacy of repeated doses of REGENECYTE, an allogeneic hematopoietic progenitor cell (HPC) therapy derived from cord blood, in patients with post-COVID syndrome.<br><br>METHODS: In this randomized, single-blind, placebo-controlled, phase IIa trial, we evaluated repeated intravenous infusions of REGENECYTE from different donors (without HLA matching) in patients with post-COVID syndrome in the USA. Eligible adults aged 18-65 years had persistent post-COVID symptoms between 6 and 18 months and tested negative for SARS-CoV-2 within 7 days before enrollment. Participants were randomized into a 2:1 ratio to receive either REGENECYTE or placebo. Three infusions were administered over 6 weeks, 3 weeks apart, followed by a 20-week follow-up. Each dose of REGENECYTE contains at least 1 &#xd7; 10[7] total nucleated cells (TNC)/kg, with a cumulative dose of at least 3 &#xd7; 10[7] TNC/kg per patient. The primary endpoint was safety, assessed using the Common Terminology Criteria for Adverse Events by National Cancer Institute (NCI CTCAE) v5.0. The key secondary endpoint focused on changes in fatigue using the Chalder Fatigue Questionnaire (CFQ-11), while exploratory endpoints evaluated frailty, quality of life, and cognition using validated instruments. This trial was registered with ClinicalTrials.gov, NCT05682560.<br><br>FINDINGS: Between May 4 and Dec 26, 2023, 30 eligible patients were enrolled and completed the study. The mean age was 41.9 years; 70% were female. The average duration of post-COVID symptoms was 306 days. Only 2 patients (10%) in the REGENECYTE group experienced mild treatment-emergent adverse events (TEAEs), indicating good tolerability. Notably, REGENECYTE significantly and sustainably improved fatigue symptoms, as measured by CFQ-11 Bimodal and Likert scores, compared to placebo (p < 0.01). Improvements were observed as early as week 6 and persisted through the 20-week follow-up. The most pronounced benefit was seen in the physical fatigue domain. REGENECYTE also improved quality of life in domains such as usual activities and mental wellbeing. There were no significant changes in frailty or cognitive scores.<br><br>INTERPRETATION: REGENECYTE was well tolerated and safe when administered as repeat infusions from unmatched cord blood donors. It produced a meaningful and durable reduction in fatigue symptoms, the most burdensome feature of post-COVID syndrome-highlighting its potential as a novel therapeutic strategy. These findings support further clinical development of cord blood-based therapies targeting fatigue in post-COVID and potentially other fatigue-related conditions.<br><br>FUNDING: StemCyte International, Ltd.},
}
@article {pmid41625797,
year = {2025},
author = {Puthenveedu, VK and Prabhakaran, ST and Basheer, A},
title = {Clinical Spectrum and Outcomes of Post-COVID Syndrome Among Adults in Rural Kerala: A Cohort Study.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100434},
pmid = {41625797},
issn = {2168-8184},
abstract = {Background Post-COVID syndrome (PCS) is a condition that affects some individuals who have recovered from COVID-19, characterized by persistent symptoms that last for weeks or months after the acute illness has resolved. Despite ongoing research on PCS, key gaps remain, including short follow-up, absence of control groups, small sample sizes, and limited representation of mild-to-moderate cases. Objectives The objective of this study is to determine the incidence proportion and outcomes of PCS over 12 months in a rural district of Kerala. Methods A prospective cohort study was conducted among 596 participants, of which 298 had a previous COVID-19 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or antigen test (exposure group), while the remaining had no evidence of COVID-19 (control group). Field workers collected data by direct interviews. Study variables, including blood pressure (BP), blood sugar, oxygen (O2) saturation, and six-minute walk distance (6MWD), were recorded at six, nine, and 12 months following recruitment. Results The incidence proportion of PCS was 91.9% (95% CI: 88.8-95.0%) in the exposure cohort (i.e., 274/298) compared to 83.2% (95% CI: 79.0-87.4%) in the controls (i.e., 248/298) at six months. The differences in the incidence proportion of PCS between the groups were statistically significant. The differences in mean 6MWD at six, nine, and 12 months were statistically significant (p = 0.037), with a nadir at nine months. Mean systolic and diastolic BP were significantly higher in the exposure group than the control group at six and nine months, which converged by 12 months. Conclusion The persistence of symptoms and functional impairments was common among both the exposure and control groups, though more frequent in the exposure (COVID-19) group. The findings suggest that post-COVID morbidity may overlap with the background community symptom burden. Further, multicenter studies with serology and adjusted analyses are required to refine pathways for screening and long-term care.},
}
@article {pmid41625057,
year = {2026},
author = {Hirobumi, I},
title = {Epipharyngeal Abrasive Therapy (EAT) Improved Premature Ventricular Contractions (PVCs) and Brain Fog Associated With Long COVID: A Case Report.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e102533},
pmid = {41625057},
issn = {2168-8184},
abstract = {A 50-year-old man with premature ventricular contractions (PVCs) detected before coronavirus disease 2019 (COVID-19) infection developed persistent fatigue and brain fog following COVID-19, which caused difficulty in continuing his work. Epipharyngeal abrasive therapy (EAT) was started without pharmacological treatment. Serial Holter electrocardiography demonstrated a marked reduction in PVC burden after continued EAT. In contrast, improvement in brain fog and recovery of work motivation occurred at a later stage, eventually allowing him to return to work. PVCs are considered an autonomic-sensitive peripheral manifestation, whereas brain fog likely represents dysfunction of central autonomic networks. The temporal dissociation observed between early improvement in PVCs and delayed cognitive recovery indicates that EAT may exert time-dependent effects on peripheral and central autonomic regulation. This case suggests that EAT could serve as a non-pharmacological and minimally invasive therapeutic option for both peripheral and central symptoms associated with autonomic dysfunction in Long COVID.},
}
@article {pmid41624858,
year = {2025},
author = {Charles James, J and Teegen, B and Pakeerathan, T and Hütter, G and Ladopoulos, T and Siems, N and Trampe, N and Ayzenberg, I and Gold, R and Faissner, S},
title = {Anti-VGLUT2 autoantibodies associated with post-COVID neurocognitive dysfunction: a case report.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1731744},
pmid = {41624858},
issn = {1664-3224},
mesh = {Humans ; Male ; *COVID-19/complications/immunology ; *Autoantibodies/blood/immunology ; Adult ; *SARS-CoV-2/immunology ; *Cognitive Dysfunction/immunology/etiology ; Neuropsychological Tests ; Immunoglobulins, Intravenous/therapeutic use ; },
abstract = {Post-COVID-19 syndrome (PCS) is frequently associated with fatigue and cognitive dysfunction, while underlying mechanisms remain unclear. We report a 44-year-old male with persistent symptoms following SARS-CoV-2 infection, including severe cognitive and motor fatigue, word-finding difficulties, and impaired concentration. Neuropsychological testing revealed marked deficits in alertness, attention, fluency, and processing speed. Serum analysis demonstrated anti-VGLUT2 autoantibodies. IVIG therapy yielded subjective but no objective improvement. This appears to be the first PCS case associated with VGLUT2 autoantibodies and raises the hypothesis of a potential pathophysiological link that requires confirmation in larger cohorts.},
}
@article {pmid41623576,
year = {2026},
author = {Birla, S and Angural, A and Madathumchalil, A and Shende, RV and Shastry, SV and Shekar, PK and Mahadevappa, M and Vishwanath, P and Prashant, A},
title = {"Bridging the clinical, molecular and genetic perspectives on myocarditis in post-COVID-19 era".},
journal = {International journal of cardiology. Cardiovascular risk and prevention},
volume = {28},
number = {},
pages = {200576},
pmid = {41623576},
issn = {2772-4875},
abstract = {Myocarditis is a non-familial inflammatory manifestation of the myocardium, primarily induced by viral infections, but it may also stem from bacterial pathogens, autoimmune disorders, or adverse drug reactions. Its diagnosis remains challenging due to heterogeneous and often non-specific clinical presentations. Recent epidemiological studies have indicated a markedly increased incidence of myocarditis following SARS-CoV-2 infection and mRNA COVID-19 vaccinations (to a lesser extent) compared to pre-pandemic statistics. While a significant number of cases follow a mild and self-limiting disease course, severe manifestations can lead to arrhythmias, heart failure, or even sudden cardiac death. Importantly, accumulating evidence indicates that even mild myocarditis confers an elevated long-term risk of adverse cardiovascular outcomes. Beyond clinical and imaging-based observations, recent advances highlight a critical role for host genetic susceptibility in modulating immune responses, myocardial injury, and disease severity. This review provides a comprehensive synthesis of the etiology, pathophysiological mechanisms, clinical spectrum, diagnostic approaches, and evidence-based management of COVID-19-associated myocarditis, while critically integrating emerging genetic and transcriptomic insights that may explain disease heterogeneity, variable inter-individual susceptibility, and long-term prognosis. By bridging clinical aspects with molecular and genetic frameworks, this review underscores the importance of personalized risk stratification, vigilant post-recovery surveillance, and targeted preventive strategies in the post-pandemic era.},
}
@article {pmid41621351,
year = {2026},
author = {Sarkanen, T and Merikanto, I and Bjorvatn, B and Chung, F and Holzinger, B and Morin, CM and Penzel, T and De Gennaro, L and Wing, YK and Benedict, C and Xue, P and Reis, C and Korman, M and Landtblom, AM and Matsui, K and Hrubos-Strøm, H and Mota-Rolim, S and Nadorff, MR and Berezin, L and Liu, Y and Scarpelli, S and Brandao, LE and Cedernaes, J and Partinen, E and Bolstad, CJ and Plazzi, G and Espie, CA and Partinen, M and Dauvilliers, Y},
title = {Corrigendum to "Long COVID as a risk factor for hypersomnolence and fatigue: insights from the 2nd International Covid Sleep Study Collaboration (ICOSS-2)" [Sleep Med. 136 (2025) 106764].},
journal = {Sleep medicine},
volume = {140},
number = {},
pages = {108798},
doi = {10.1016/j.sleep.2026.108798},
pmid = {41621351},
issn = {1878-5506},
}
@article {pmid41613157,
year = {2025},
author = {Falco, P and Galosi, E and Litewczuk, D and Evangelisti, E and Di Stefano, G and Arendt-Nielsen, L and Truini, A and Leone, CM},
title = {Autonomic small fiber involvement in painful long COVID: a histological and clinical study.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1719705},
pmid = {41613157},
issn = {1662-5161},
abstract = {BACKGROUND: Despite growing recognition of painful long COVID syndrome as a chronic neurological condition marked by pain and autonomic symptoms, the precise contribution of autonomic small fiber involvement is still not well characterized and understood. In this retrospective study, we aimed to identify autonomic small fiber involvement in patients with painful long COVID syndrome by analyzing skin biopsy data. We used nerve fiber density in the piloerector muscles (PMNFD) and sweat glands (SGNFD) as the primary histological outcomes of autonomic innervation.<br><br>METHODS: We reviewed skin biopsy samples from 50 patients with painful long COVID syndrome and included 31 patients with available PMNFD and SGNFD data for analysis. PMNFD and SGNFD were compared with an age- and sex-matched healthy control group (n = 42). To evaluate whether autonomic involvement was independent of somatic nerve fiber reduction, a subgroup analysis was performed in patients with normal intraepidermal nerve fiber density (IENFD) (n = 23). Correlations between histological findings and autonomic symptoms, assessed with the COMPASS-31 questionnaire, were also analyzed.<br><br>RESULTS: Piloerector muscle nerve fiber density and SGNFD were significantly reduced in patients with long COVID compared with controls, both in the full sample (p = 0.0135; p < 0.0001) and in the subgroup with normal IENFD (p = 0.0003; p = 0.0005). Neither PMNFD nor SGNFD correlated with COMPASS-31 scores (p = 0.27; p = 0.46) and no association with disease onset, duration and COVID-19 severity was found.<br><br>CONCLUSION: These findings provide histological evidence that autonomic small fiber damage is a prominent and measurable feature of painful long COVID syndrome. Importantly, this pathology was also observed in patients with preserved IENFD, indicating that autonomic involvement may occur independently of somatic small fiber loss.},
}
@article {pmid41612939,
year = {2026},
author = {Pang, H and Frontera, J and Jiang, L and Li, C and Boutajangout, A and Sun, Z and Debure, L and Ghuman, M and Vedvyas, A and Masurkar, AV and Wisniewski, T and Ge, Y},
title = {Choroid plexus alterations in long COVID and their associations with Alzheimer's disease risks.},
journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71020},
pmid = {41612939},
issn = {1552-5279},
support = {R01AG077422//The National Institutes of Health/National Institute on Aging/ ; U24 NS135568/NS/NINDS NIH HHS/United States ; P30AG066512//The National Institutes of Health/National Institute on Aging/ ; R01AG077422/GF/NIH HHS/United States ; U24 NS135568/GF/NIH HHS/United States ; P30AG066512/GF/NIH HHS/United States ; },
mesh = {Humans ; *Choroid Plexus/diagnostic imaging/pathology ; *Alzheimer Disease/diagnostic imaging ; Female ; Male ; Aged ; *COVID-19/complications/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Cerebrovascular Circulation/physiology ; tau Proteins/blood ; Biomarkers/blood ; Middle Aged ; Aged, 80 and over ; Cognitive Dysfunction ; },
abstract = {INTRODUCTION: Choroid plexus (ChP) enlargement is a neuroimaging biomarker of neuroinflammation and neurodegeneration. However, evidence of ChP structural and perfusion alterations in long coronavirus disease (COVID) and their clinical relevance remains limited.<br><br>METHODS: This study included 86 long COVID, 67 recovered COVID, and 26 COVID-negative healthy controls (HCs). ChP volume and cerebral blood flow (CBF) were quantified, and their associations with Alzheimer's disease (AD) symptoms and plasma biomarkers were examined.<br><br>RESULTS: Both patient groups showed higher ChP volume and lower CBF than HC. Relative to recovered COVID, long COVID patients had a larger ChP volume, but no significant difference in CBF. ChP volume correlated positively with glial fibrillary acidic protein (r&#xa0;=&#xa0;0.35) and phosphorylated tau217 (p-tau217; r&#xa0;=&#xa0;0.54), while CBF correlated negatively with p-tau217 (r&#xa0;=&#xa0;-0.56). Both ChP volume and CBF were associated with cognitive decline measured with Mini-Mental State Examination and Clinical Dementia Rating.<br><br>DISCUSSION: These findings suggest that ChP differences in long COVID are associated with AD-related cognitive decline and increased plasma biomarkers.<br><br>HIGHLIGHTS: Long coronavirus disease (COVID) patients show choroid plexus (ChP) enlargement and reduced cerebral blood flow. ChP alterations are associated with Alzheimer's disease (AD)-related symptoms and plasma biomarker changes. ChP alterations on magnetic resonance imaging may serve as imaging markers for tracking neurological symptoms and AD-related pathology in post-COVID patients.},
}
@article {pmid41612118,
year = {2026},
author = {Goldschmidt, MI and Mkoma, GF and Petersen, JH and Agyemang, C and Rostila, M and Thaning, P and Hansen, EF and Benfield, T and Norredam, M},
title = {Ethnic Differences in Symptom Burden, Work and Daily Life: A Study of Long COVID Patients in Denmark.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41612118},
issn = {1525-1497},
abstract = {BACKGROUND: Ethnic minorities appear to be at higher risk of long COVID. Our objective was to estimate ethnic differences in the burden of long COVID symptoms and their impact on daily life and occupational status.<br><br>METHODS: Retrospective cohort study of adults (&#x2265;&#x2009;18&#xa0;years) admitted to a Long COVID Clinic, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark, from February 2021 through November 2022. Data from symptom questionnaires were linked to clinical data from patient records and national register data. Using regression models, we calculated the burden and number of long COVID symptoms as well as the risk of certain symptom categories, of being on sick leave, of loss of independence, and of having returned to usual leisure activities.<br><br>RESULTS: A total of 864 patients from the long COVID clinic were included; hereof 31.2% were ethnic minorities. Compared to patients of Danish origin, ethnic minorities had an 18.32% higher mean burden of long COVID symptoms (adjusted mean difference (MDadj) 3.23, 95% confidence interval&#xa0;(CI): 1.67;4.78) and experienced 18.56% more long COVID symptoms on average (MDadj 1.56, 95% CI: 0.86;2.26). Ethnic minorities were more likely to experience cardio-pulmonary, psychological, and gastrointestinal symptoms. However, compared to patients of Danish origin, ethnic minorities had lower odds of being on sick leave (adjusted odds ratio (ORadj) 0.61, 95% CI: 0.40;0.94) and of having returned to usual leisure activities (ORadj 0.68, 95% CI: 0.48;0.94).<br><br>CONCLUSIONS: Ethnic minorities experienced a higher number and symptom burden of long COVID symptoms along with a higher risk of certain symptom categories, notably psychological symptoms. However, ethnic minorities had lower odds of being on sick leave. Additional research is needed into the explanations of the disparities identified in this study.},
}
@article {pmid41611926,
year = {2026},
author = {Dos Santos Pinto, A and Mwangi, VI and Neves, JCF and Maciel, ABS and Neto, AV and da Silva Valente, J and de Melo, GC and Monteiro, WM and de Souza Sampaio, V and da Costa, AG and Almeida-Val, FF},
title = {Clinical features and inflammatory signatures of patients with persistent gastrointestinal long COVID two years after severe SARS-CoV-2 infection.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {6620},
pmid = {41611926},
issn = {2045-2322},
support = {Doctorate scholarship//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; PDJ scholarship (175855/2023-4)//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq/MCTI/ CT-Saude Call - Research, development and innovation in long COVID); notice n&#xb0;53/2022 (RECLAIM Brazil Study)//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; Call No. 038/2022 - PDPG/CAPES/FAPEAM//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado do Amazonas/ ; Call No. 006/2020 - PCTI-EMERGESA&#xda;DE/AM - Priority Areas//Funda&#xe7;&#xe3;o de Amparo a Pesquisa do Estado do Amazonas (FAPEAM)/ ; },
abstract = {Persistent gastrointestinal (GI) symptoms are increasingly recognized as part of long COVID, yet their underlying mechanisms remain poorly defined. We conducted an exploratory case-series study of 80 adults hospitalized with severe COVID-19 in March-May 2020 in Manaus, Brazil. Two years post-infection, participants underwent structured clinical interviews and longitudinal cytokine analysis (IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α). Overall, 30 participants reported ongoing GI symptoms (GI group) predominantly gastroesophageal reflux (63%), abdominal pain (43%), and diarrhea (37%). Compared with participants without GI symptoms (nGI group, n = 50), the GI group reported a higher burden of additional long COVID symptoms, including palpitations, headache, and arthralgia. They also exhibited distinct clinical and laboratory features, including lower baseline creatinine and ferritin levels and altered platelet indices. Although IL-6 levels were lower during the acute hospitalization phase, they became significantly elevated at four months post-infection (D120, p = 0.005), suggesting delayed inflammatory response. Ascendent biomarker analysis identified TNF-α as highly expressed in a large proportion of GI group. The findings suggest GI problems can persist two years after severe COVID-19, and long-term inflammatory dysregulation may underlie the pathogenesis of these GI manifestations in long COVID. Prolonged gastrointestinal surveillance in COVID-19 survivors is necessary.},
}
@article {pmid41610163,
year = {2026},
author = {Morad, H and Vanhala, T and Kisiel, MA and Andreason, A and Li, M and Andersson, G and Laurell, G and Finger, TE and Hellekant, G},
title = {Taste dysfunction in long COVID.},
journal = {Chemical senses},
volume = {51},
number = {},
pages = {},
doi = {10.1093/chemse/bjaf068},
pmid = {41610163},
issn = {1464-3553},
mesh = {Humans ; Male ; *COVID-19/complications ; Female ; *Taste Disorders/etiology/pathology/virology/physiopathology/metabolism ; Middle Aged ; Taste Buds/pathology/metabolism ; Adult ; Aged ; SARS-CoV-2 ; Taste/physiology ; },
abstract = {Persistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subjects diagnosed with COVID-19 who experienced taste disturbances more than 12 mo after testing positive for SARS-CoV-2. To objectively establish the nature of the taste deficit, we used the WETT taste test, which quantifies the subject's ability to taste each of the 5 taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied 5 to 8 fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud (TB) structure and innervation and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only 3 showed overall taste scores below the 10th percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLCβ2-dependent taste qualities (sweet, umami, and bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved TB structure and innervation but with occasional disorganized TBs and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely-more frequently involving PLCβ2-dependent taste qualities-but is not due to wholesale disruption of the taste periphery.},
}
@article {pmid41608911,
year = {2026},
author = {Bramante, CT and Boulware, DR},
title = {Preventing Long COVID With Metformin.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf700},
pmid = {41608911},
issn = {1537-6591},
support = {K23DK124654/NH/NIH HHS/United States ; K24AI184270/NH/NIH HHS/United States ; },
}
@article {pmid41608121,
year = {2026},
author = {Gilbert, KM and Aglan, M and Jogdand, A and Khairnar, NV and Ssemaganda, H and Ong, MS and Farmer, JR},
title = {Nirmatrelvir/ritonavir use reduces risk for long COVID in patients with immunodeficiency.},
journal = {Journal of human immunity},
volume = {2},
number = {1},
pages = {e20250107},
pmid = {41608121},
issn = {3065-8993},
abstract = {Our retrospective study highlights that acute use of nirmatrelvir/ritonavir significantly reduces the risk of post-acute sequelae of SARS-CoV-2 infection (long COVID) in immunodeficient patients, emphasizing the need for clinical trials that include this high-risk population.},
}
@article {pmid41605818,
year = {2026},
author = {Keels, JN and LaPlante, RD and Lee, CS and Dwyer, AA},
title = {Prevalence of new-onset diabetes following COVID-19 infection: A systematic review and meta-analysis.},
journal = {Diabetes, obesity &amp; metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1111/dom.70508},
pmid = {41605818},
issn = {1463-1326},
support = {1F31NR021624-01/NR/NINR NIH HHS/United States ; },
abstract = {AIM: To estimate the prevalence of new-onset diabetes in adults (≥ 18 years) following SARS-CoV-2 infection.<br><br>MATERIALS AND METHODS: This meta-analysis includes studies written in English that measured the number of adults (&#x2265;&#x2009;18&#x2009;years) diagnosed with diabetes following SARS-CoV-2 infection. Studies underwent dual independent review; quality was assessed by using the New Castle Ottawa Scale. A random-effects meta-analysis was conducted to obtain the pooled estimate of new-onset diabetes. To understand the relationship between patient characteristics (age, sex) and study variable (duration of follow-up), a random effects meta-regression was used.<br><br>RESULTS: A total of 33 articles were retained for analysis. The overall estimated prevalence of new-onset diabetes (combined T1DM and T2DM or undefined) was 8.33% (95% CI 7.47, 9.18%, z&#x2009;=&#x2009;19.04, p&#x2009;<&#x2009;0.001; Q&#x2009;=&#x2009;6791.24, I[2], 99.68%). The overall estimated prevalence of new-onset T2DM in COVID-19 was 8.92% (95% CI 7.88%, 9.96%, z&#x2009;=&#x2009;16.77, p&#x2009;<&#x2009;0.001; Q&#x2009;=&#x2009;27659.74; p&#x2009;<&#x2009;0.001, I[2]&#x2009;=&#x2009;99.96%). The overall estimated prevalence of new-onset T1DM was 0.86% (95% CI 0.0072%, 0.0099%, z&#x2009;=&#x2009;12.59, p&#x2009;<&#x2009;0.001; Q&#x2009;=&#x2009;9456.28; p&#x2009;<&#x2009;0.001, I[2]&#x2009;=&#x2009;99.94%). At the study level, there was no significant relationship identified with age, sex, or follow-up duration.<br><br>CONCLUSIONS: This systematic review and meta-analysis revealed a notable increase in T2DM or combined (T1DM, T2DM, or undefined) conditions. As such, it may be important to understand the underlying factors contributing to increased prevalence.},
}
@article {pmid41605350,
year = {2026},
author = {Gerhards, SK and Luppa, M and Zülke, A and Sander, C and Schomerus, G and Buechner, R and Wirkner, K and Reusche, M and Zeynalova, S and Lehmann, J and Baber, R and Obrig, H and Herzig, S and Thöne-Otto, A and Witte, AV and Villringer, A and Fricke, C and Bergh, FT and Saur, D and Schroeter, ML and Löffler, M and Engel, C and Riedel-Heller, SG},
title = {Depressive and anxiety symptoms in individuals with Long-COVID: Does social network matter? - Results of a German Long-COVID study.},
journal = {Journal of affective disorders},
volume = {401},
number = {},
pages = {121272},
doi = {10.1016/j.jad.2026.121272},
pmid = {41605350},
issn = {1573-2517},
mesh = {Humans ; Male ; *COVID-19/psychology/epidemiology ; Female ; Germany/epidemiology ; Middle Aged ; *Anxiety/psychology/epidemiology ; Adult ; *Depression/psychology/epidemiology ; *Social Support ; *Social Networking ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: Some patients previously infected with SARS-CoV-2 develop symptoms that are summarized under the term Long COVID (LC). There is limited evidence on how social characteristics influence depressive and anxiety symptoms in adults with LC.<br><br>METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). Anxiety symptoms were measured using the Generalized Anxiety Disorder Scale (GAD-7). The living situation (alone vs. with someone) was assessed by a single question. The social network was assessed using the Lubben Social Network Scale (LSNS). Multivariate regression analysis was performed.<br><br>RESULTS: In n&#xa0;=&#xa0;410 participants with LC (mean age = 47.12, SD = 12.24) from Leipzig, Germany, we found that living with others was associated with fewer depressive symptoms compared to living alone (B&#xa0;=&#xa0;-2.18, p&#xa0;=&#xa0;.011). A larger social network was associated with fewer anxiety symptoms in adults with LC symptoms (IRR&#xa0;=&#xa0;0.99, p&#xa0;=&#xa0;.008).<br><br>CONCLUSION: Social factors, such as social network and living situation, are associated with mental health factors like depressive and anxiety symptoms in adults with LC. Further research is required in order to elucidate the complex interplay between social factors and mental health in people with LC in the context of longitudinal studies. Future research directions are discussed.},
}
@article {pmid41603315,
year = {2026},
author = {Petry Moecke, DM and Kwong, EH and Cressman, S and Yao, J and Singh, C and Taylor, C and Camp, PG},
title = {Rehabilitation needs of long COVID patients in British Columbia.},
journal = {PM &amp; R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70092},
pmid = {41603315},
issn = {1934-1563},
support = {//Ministry of Health, British Columbia/ ; //British Columbia Lung Foundation/ ; //UBC Post-COVID Interdisciplinary Clinical Care Network with St. Paul's Foundation/ ; },
abstract = {INTRODUCTION: COVID-19 can result in persistent symptoms and functional impairment that significantly impact daily functioning, highlighting the need for targeted rehabilitation. However, there is a lack of data on what proportion of long COVID patients need rehabilitation and which types are required.<br><br>OBJECTIVE: To estimate the rehabilitation needs of patients with long COVID.<br><br>DESIGN: Retrospective, cross-sectional analysis of clinical data.<br><br>SETTING: Post-COVID recovery clinic in British Columbia, Canada.<br><br>PARTICIPANTS: Individuals with long COVID, defined as having symptoms persisting beyond 3 months post infection, with the first clinic visit occurring within 6 months post infection.<br><br>INTERVENTION: Not applicable.<br><br>MAIN OUTCOME MEASURES: We created thresholds based on objective tests and patient-reported outcomes to determine rehabilitation needs.<br><br>RESULTS: Data from 3709 patients who visited the clinic between March 2020 and May 2023 were available for analysis; 33% met the study eligibility criteria (n&#x2009;=&#x2009;1237). Patients were primarily women (65%) and white (57%), with a mean age of 49&#x2009;&#xb1;&#x2009;14&#x2009;years. Two thirds had required hospitalization. The average time from infection to clinic visit was 136&#x2009;&#xb1;&#x2009;34&#x2009;days. At 3-6&#x2009;months post infection, the most common COVID-19 symptoms were fatigue, dyspnea, muscle weakness, and muscle/joint aches. Most patients exceeded the rehabilitation threshold for dyspnea (83%), fatigue (78%), frailty (74%), and posttraumatic stress disorder (58%). Quality of life was impaired for 80%. Neuropsychological symptoms like anxiety (42%) and depression (36%) were also prevalent. Reductions in 6-minute walk distance (&#x2265;25%) and sit-to-stand performance (&#x2265;50%) occurred in 26% and 55% of patients, respectively. The majority of participants (98%) exceeded at least one test threshold for rehabilitation, and most (85%) were eligible for more than one type. The most required types of rehabilitation were pulmonary rehabilitation (83%), mental health support (78%), and neurorehabilitation (70%).<br><br>CONCLUSION: The need for rehabilitation services among individuals experiencing long COVID in British Columbia is substantial. Use of predefined thresholds that incorporate measures of both symptom burden and functional impairment can effectively support the identification of high-need patients and their overall rehabilitation needs. Combined with clinicians' expertise, this approach can facilitate timely, evidence-based referrals to specialized care for those who need it.},
}
@article {pmid41602330,
year = {2025},
author = {Arroyo-Romero, S and Gómez-Sánchez, L and Suárez-Moreno, N and Navarro-Cáceres, A and Domínguez-Martín, A and Lugones-Sánchez, C and González-Sánchez, S and Sánchez-Moreno, A and Rodríguez-Sánchez, E and García-Ortiz, L and Navarro-Matias, E and Gómez-Marcos, MA},
title = {Association between cardiovascular, psychotropic and anti-inflammatory/analgesic drug use and vascular dysfunction in individuals with long COVID. BioICOPER study.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1691153},
pmid = {41602330},
issn = {2297-055X},
abstract = {INTRODUCTION: While the deterioration in the general health of patients with long COVID (LC) is well documented, no studies have assessed changes in medication use and their relationships with vascular health. This study aimed to evaluate the increase in the use of various drug classes in LC and its relationship with vascular structure and function.<br><br>METHODS: Each participant in the sample of 305 subjects diagnosed with LC completed a questionnaire on medication use, verified in medical records. Pre-pandemic and current drug use were recorded. Arterial stiffness was measured with the VaSera device, which estimates the cardio-ankle vascular index and brachial-ankle pulse wave velocity (ba-PWV); carotid-femoral pulse wave velocity was determined using the Sphygmocor device. Vascular structure was assessed by carotid intima-media thickness (c-IMT), measured with a Sonosite Micromax ultrasound. This analysis focuses exclusively on macrovascular parameters. Statistical analyses were performed with SPSS software.<br><br>RESULTS: Use of all classes of medication increased. Patients with a greater rise in drug use after an LC diagnosis showed higher vascular parameters. Greater cardiovascular drug use was positively associated with ba-PWV, an indicator of arterial stiffness (&#x3b2;&#x2009;=&#x2009;0.301, 95%CI: 0.024-0.577). Increased anti-inflammatory/analgesic drug use was positively associated with c-IMT, a marker of vascular wall thickness (&#x3b2;&#x2009;=&#x2009;0.012, 95%CI: 0.001-0.023).<br><br>CONCLUSIONS: Medication use rose from 2019 to the time of inclusion in the study. The increase in cardiovascular and anti-inflammatory/analgesic drug use was positively associated with ba-PWV and c-IMT, respectively, suggesting a link between greater drug use and impaired vascular health in LC.},
}
@article {pmid41601165,
year = {2026},
author = {Amato, C and Iovino, P and Spinicci, M and Longobucco, Y and Livi, L and Giovannoni, L and Guidotti, C and Pietrini, L and Braschi, F and De Filippis, C and Ermini, L and Gori, L and Zocchi, C and Argirò, A and Bartoloni, A and Olivotto, I and Lavorini, F and Marchionni, N and Fattirolli, F and Rasero, L},
title = {Factors associated with persistent symptoms after COVID-19 infection: a longitudinal study on an Italian cohort of patients discharged from hospital.},
journal = {Infectious diseases (London, England)},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/23744235.2026.2620811},
pmid = {41601165},
issn = {2374-4243},
abstract = {BACKGROUND: Although the acute phase of the COVID-19 pandemic has subsided, long COVID remains a significant and ongoing public health concern. Persistent symptoms continue to affect a substantial proportion of COVID-19 survivors, increasing healthcare burden.<br><br>OBJECTIVE: This study aims to identify the determinants of long-term symptom trajectories following COVID-19 infection.<br><br>METHODS: We conducted a prospective cohort study of 1666 adults discharged after hospitalisation for COVID-19 in Tuscany, Italy. The presence of mental confusion, exertional dyspnoea, fatigue, and insomnia was assessed at 1, 3, 6, 9, and 12&#x2009;months post-discharge. The mean hospital stay was 13.6 (&#xb1;12) days and 131 patients required intensive care unit admissions. Latent growth curve models were used to examine the baseline prevalence and longitudinal trajectories of each symptom, and to identify demographic and clinical factors associated with symptom persistence.<br><br>RESULTS: Fatigue was the most common persistent symptom at baseline, followed by exertional dyspnoea, insomnia, and mental confusion. Female sex was consistently associated with both baseline presence and persistence of all symptoms. Older age was linked to baseline mental confusion and to persistent dyspnoea and fatigue. Markers of greater acute severity (ICU admission, longer hospital stay, higher WHO score) were associated with symptom improvement over time. Pre-existing coronary heart disease and cancer independently predicted persistent dyspnoea and fatigue, whereas hypertension appeared protective.<br><br>CONCLUSIONS: Persistent symptoms are common after COVID-19 and vary by sex, age, comorbidities, and acute disease features. Symptoms may persist up to 12 months post-hospitalisation, underscoring the need for long-term follow-up and targeted interventions.},
}
@article {pmid41600912,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Saldanha-Araujo, F and Argañaraz, GA and Argañaraz, ER},
title = {Correction: de Melo et al. SARS-CoV-2 Spike Protein and Long COVID-Part 1: Impact of Spike Protein in Pathophysiological Mechanisms of Long COVID Syndrome. Viruses 2025, 17, 617.},
journal = {Viruses},
volume = {18},
number = {1},
pages = {},
pmid = {41600912},
issn = {1999-4915},
abstract = {Error in Funding [...].},
}
@article {pmid41600911,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER},
title = {Correction: de Melo et al. SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome. Viruses 2025, 17, 619.},
journal = {Viruses},
volume = {18},
number = {1},
pages = {},
pmid = {41600911},
issn = {1999-4915},
abstract = {In the original publication [...].},
}
@article {pmid41599072,
year = {2026},
author = {Dave, RS and Fox, HS},
title = {Synergy of SARS-CoV-2 and HIV-1 Infections in the Human Brain.},
journal = {Pathogens (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
pmid = {41599072},
issn = {2076-0817},
mesh = {Humans ; *COVID-19/virology/pathology/complications/epidemiology ; *HIV Infections/virology/pathology/complications ; *SARS-CoV-2 ; *HIV-1 ; *Brain/virology/pathology ; Microglia/virology/pathology ; Coinfection/virology ; Cytokines/metabolism ; },
abstract = {This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes.},
}
@article {pmid41598609,
year = {2026},
author = {Balan, OV and Malysheva, IE and Tikhonovich, EL and Lysenko, LA},
title = {Dysregulation of MMP-2 and MMP-9 in Post-COVID-19 and IPF: Correlations with Systemic Inflammation and Endothelial Dysfunction.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
pmid = {41598609},
issn = {2077-0383},
abstract = {Background/Objectives: Post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF) exhibit significant clinical and pathophysiological overlap, suggesting convergent molecular pathways driving fibrosis. This prospective longitudinal study investigates the sustained dysregulation of matrix metalloproteinases (MMP)-2 and MMP-9 and its relationship with evolving systemic inflammation and endothelial dysfunction in convalescent COVID-19 patients, with comparative analysis to IPF. Methods: We conducted a prospective observational study of 86 patients at 6 and 12 months post-SARS-CoV-2 infection, stratified by high-resolution CT evidence of PCPF (FB+ group, n = 32) or absence of fibrosis (FB- group, n = 54). Gene expression of MMP-2 and MMP-9 in peripheral blood leukocytes and circulating levels of MMP-2, MMP-9, pro-inflammatory cytokines (TNF-α, IL-6), and endothelial dysfunction markers (Endothelin-1 [ET-1], adhesion molecules) were quantified via qRT-PCR and ELISA. A pre-pandemic healthy control group (HD, n = 20) and an IPF patient group (n = 10) served as comparators. Results: A significant, sustained elevation of MMP-2 and MMP-9 was observed in all post-COVID-19 patients versus HDs, most pronounced in the FB+ group and qualitatively similar to IPF. A critical divergence emerged: FB- patients showed resolution of systemic inflammation (reduced TNF-α, IL-6), whereas FB+ patients exhibited persistent cytokine elevation. Critically, a delayed, severe endothelial dysfunction, characterized by a profound surge in ET-1 and elevated adhesion molecules, manifested exclusively in the FB+ cohort at 12 months. Positive correlations linked plasma MMP-2/9 levels with ET-1 (rs = 0.65, p = 0.004; rs = 0.49, p = 0.009) and ET-1 with sICAM-1 (rs = 0.68, p = 0.01). Conclusions: The development of PCPF is associated with a distinct pathogenic triad: sustained MMP dysregulation, failure to resolve inflammation, and severe late-phase endothelial dysfunction. The correlative links between these components suggest a self-reinforcing loop. This systemic signature mirrors patterns in IPF, underscoring shared final pathways in fibrotic lung disease and identifying the MMP-inflammation-endothelial axis as a promising target for biomarker development and therapeutic intervention.},
}
@article {pmid41598473,
year = {2026},
author = {Goicoechea-Calvo, A and Navarro Expósito, N and Coll-Fernández, R and Colomer Giralt, M and Martín Saavedra, A and González-Aumatell, A and Méndez-Hernández, M and Carreras-Abad, C and Moreira, M and Giralt-López, M and Pallarès, N and Tebe Cordomi, C and Rodríguez-Palmero, A and Rodrigo, C and Mata, MJD},
title = {Impact of Pulmonary Rehabilitation on Physical, Mental Health and Quality of Life in Children with Post-COVID-19 Condition: A 12-Month Quasi-Experimental Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
pmid = {41598473},
issn = {2077-0383},
abstract = {Background/Objectives: Evidence on pulmonary rehabilitation (PR) in paediatric post-COVID-19 condition (PPCC) is scarce. This study aimed to evaluate the association of a PR programme with changes in physical and mental health and quality of life in PPCC over a 12-month follow-up. Methods: A quasi-experimental pre-post single-arm study was conducted, with no control group, in PPCC patients attending an outpatient PR unit. The primary outcome was change in exercise capacity (6 min walk test, 6MWT). Secondary outcomes included inspiratory and peripheral muscle strength, quadriceps muscle morphology by ultrasound, fatigue, physical activity, quality of life, and psychiatric symptoms, assessed using validated paediatric instruments. Results: A total of 115 PPCC patients (mean age 13.3 years; 66.1% female) completed the PR. 6MWD distance increased from 509 ± 87 to 546 ± 86 (+37 m; p < 0.001; D: 0.50). Handgrip strength increased by 2.4 kg, maximal inspiratory pressure increased by 15 cmH2O, physical activity increased by 2.4 points, fatigue score improved by 9.3 points, and quality of life improved by 11 points (all p < 0.001). Rectus femoris thickness increased by 0.56 mm (p = 0.005), psychiatric symptom scores decreased by 4.5 points (p < 0.001), and rectus femoris echo-intensity decreased (p = 0.003). Conclusions: Multidisciplinary PR appears feasible and potentially effective in improving physical function, psychological well-being, and quality of life in PPCC, supporting the need for evidence-based paediatric rehabilitation.},
}
@article {pmid41597495,
year = {2026},
author = {Jiménez-Antona, C and Moreta-Fuentes, R and Varillas-Delgado, D and Moreta-Fuentes, C and Laguarta-Val, S},
title = {From Exhaustion to Empowerment: A Pilot Study on Motor Control-Based Exercise for Fatigue and Quality of Life in Long COVID-19 Patients.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {1},
pages = {},
pmid = {41597495},
issn = {1648-9144},
mesh = {Humans ; Female ; Pilot Projects ; *Quality of Life/psychology ; *COVID-19/complications/psychology/rehabilitation ; *Fatigue/therapy/etiology/rehabilitation ; Middle Aged ; *Exercise Therapy/methods ; Adult ; SARS-CoV-2 ; Aged ; },
abstract = {Background and Objectives: Long COVID-19 (LC) is a multifaceted condition characterized by persistent fatigue and impaired health-related quality of life (HRQoL). Exercise intolerance and post-exertional symptom exacerbation (PESE) pose challenges for rehabilitation. This study aimed to evaluate the effects of a 12-week core-focused plank exercise program on fatigue and HRQoL in women with LC, using validated patient-reported measures. Materials and Methods: A pilot quasi-experimental design was implemented, with non-randomized group allocation. Thirty-nine women with LC were recruited from the Madrid Long COVID Association. Participants were assigned to either an intervention group (n = 20), which completed a supervised plank-based motor control program, or a control group (n = 19), which maintained usual activity. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS), and HRQoL was measured using the EQ-5D-5L and EQ Visual Analog Scale (EQ-VAS). Body composition was evaluated via bioelectrical impedance analysis. Results: The intervention group showed significant reductions after intervention in the MFIS total scores compared to the control group, particularly in the physical (21.26 ± 6.76 vs. 25.21 ± 6.06; p < 0.001) and psychosocial domains (4.51 ± 0.41 vs. 5.21 ± 0.38; p < 0.001), without triggering PESE. EQ-VAS scores improved significantly (63.94 ± 15.33 vs. 46.31 ± 14.74; p = 0.034). No significant changes were found in body composition parameters, suggesting that benefits were driven by neuromuscular adaptations rather than morphological changes. Conclusions: A core-focused, non-aerobic exercise program effectively reduced fatigue and improved perceived health status in women with LC. These findings support the use of motor control-based interventions as a safe and feasible strategy for LC rehabilitation, particularly in populations vulnerable to PESE, suggesting clinical applicability for the rehabilitation of women with LC. Further randomized trials are warranted to confirm these results and explore long-term outcomes.},
}
@article {pmid41597249,
year = {2026},
author = {Stigliano, E and Tocci, A and Florio, R and Arena, V and Amadoro, G},
title = {Olfactory Dysfunction and Cognitive Deterioration in Long COVID: Pathomechanisms and Clinical Implications in Development of Alzheimer's Disease.},
journal = {Cells},
volume = {15},
number = {2},
pages = {},
pmid = {41597249},
issn = {2073-4409},
support = {RF-2021-12374//Italian Ministry of Health/ ; 971925//Alzheimer's Association Research Grant/ ; FOE D.M865/2019//Fondo Ordinario Enti/ ; },
mesh = {Humans ; *COVID-19/complications/pathology ; *Alzheimer Disease/etiology/pathology ; *Olfaction Disorders/etiology ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; Anosmia ; },
abstract = {Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer's Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection.},
}
@article {pmid41596479,
year = {2026},
author = {Otsuka, Y and Soejima, Y and Nakano, Y and Suyama, A and Takase, R and Oguni, K and Masuda, Y and Omura, D and Sakurada, Y and Matsuda, Y and Hasegawa, T and Honda, H and Tokumasu, K and Ueda, K and Otsuka, F},
title = {Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone.},
journal = {International journal of molecular sciences},
volume = {27},
number = {2},
pages = {},
pmid = {41596479},
issn = {1422-0067},
support = {2025//Ofuji Endocrine Medical Award/ ; 2025//Growth Science Foundation/ ; 2025//Kobayashi-Magobei Foundation/ ; },
mesh = {Humans ; Female ; *COVID-19/complications/metabolism/physiopathology ; Adult ; *Gonadotropin-Releasing Hormone/metabolism ; Retrospective Studies ; Male ; Middle Aged ; Hydrocortisone/blood ; *Hypothalamic Diseases/metabolism ; *Hypothalamus/metabolism/physiopathology ; Hypothalamo-Hypophyseal System/metabolism/physiopathology ; Thyrotropin-Releasing Hormone/metabolism ; Adrenocorticotropic Hormone/blood ; SARS-CoV-2 ; Corticotropin-Releasing Hormone/metabolism ; },
abstract = {Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic-pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (-0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements.},
}
@article {pmid41595923,
year = {2026},
author = {Bartholmae, M and Gunawardena, T},
title = {Comparison of Mental Illness Comorbidity Pre-Pandemic vs. Pandemic-Era and Associations with Clinical and Demographic Characteristics for Virginia Public Hospital Inpatient Discharges with a Substance Use Disorder.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {1},
pages = {},
pmid = {41595923},
issn = {1660-4601},
support = {Not available - I moved to a different institution and no longer have access to funds//Hampton Roads Community Foundation/ ; },
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; *Mental Disorders/epidemiology ; Middle Aged ; Adult ; Hospitals, Public/statistics &amp; numerical data ; Comorbidity ; Retrospective Studies ; Cross-Sectional Studies ; Virginia/epidemiology ; *Substance-Related Disorders/epidemiology ; Adolescent ; Young Adult ; Aged ; Patient Discharge/statistics &amp; numerical data ; SARS-CoV-2 ; Inpatients/statistics &amp; numerical data ; Pandemics ; },
abstract = {The rise in mental illnesses after the COVID-19 pandemic is well documented. However, it is not known whether the rates of mental illness comorbidity increased. The objectives of this study were to compare mental illness comorbidity rates before and after the pandemic among inpatients with SUD and to test associations between mental illness comorbidity, physical illness, and demographics. We used a retrospective cross-sectional design in a sample of inpatient discharges (N = 233,017) at Virginia public hospitals from January 2018 to December 2022. We used Z tests to compare rates of mental illness comorbidity pre- and post-pandemic and Chi-square tests to examine associations of mental illness comorbidity with physical illness and demographics. Single and comorbid mental illness significantly increased from pre- to post-pandemic, p < 0.0001. Mental illness comorbidity was significantly associated with sex, age, race, insurance, COVID-19/Long COVID, HIV/AIDS, COPD, hypertension, obesity, CVD, cancer, and diabetes (p < 0.0001). There was a significant increase in mental illness comorbidity, which was significantly associated with age, race, sex, and physical illnesses. Children/adolescents, females, American Indians, and individuals with HIV/AIDS had the highest rates of mental illness comorbidity. Public health action is needed to address the increase in complex medical needs among people with SUD.},
}
@article {pmid41595843,
year = {2025},
author = {Dhaouadi, S and Bouguerra, H and Hechaichi, A and Letaief, H and Safer, M and Aichouch, C and Zouayti, A and Bougatef, M and Neffati, A and El Mili, N and Mhadhbi, R and Bouafif Ép Ben Alaya, N},
title = {Long-Term Health Effects of COVID-19 in Tunisia, 2020-2021.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {1},
pages = {},
pmid = {41595843},
issn = {1660-4601},
mesh = {Humans ; Tunisia/epidemiology ; *COVID-19/epidemiology/complications ; Female ; Male ; Adult ; Middle Aged ; Cross-Sectional Studies ; Aged ; Prevalence ; Young Adult ; Adolescent ; SARS-CoV-2 ; Child ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; },
abstract = {Background: Some patients suffer from persistent symptoms following a COVID-19 infection, referred to as long COVID. The aims of the study were to estimate the prevalence of long COVID and study its determinants in Tunisia. Methods: We conducted a nationwide cross-sectional study among a representative sample of COVID-19 survivors residing in Tunisia between June and August 2022. We selected a random sample, stratified by age and region, among residents registered in the national surveillance database with a SARS-CoV-2 positive test taken from September 2020 to September 2021 (n = 479,743). The expected sample size was 384. We defined a patient with long COVID as having at least one self-reported symptom persisting for more than four weeks after the first confirmation of SARS-CoV-2 infection (RT-PCR or Ag-RDT) and not explained by an alternative diagnosis. Trained healthcare workers interviewed consenting respondents by phone using a structured questionnaire. We described continuous variables using median and interquartile range (IQR). We measured the prevalence of long COVID and its 95% confidence interval (95% CI). We estimated the association between explanatory variables (socio-demographic, lifestyle and comorbidities, SARS-CoV-2 history infection, COVID-19 vaccination status) and long COVID using a log-binomial model, reporting adjusted prevalence ratios (a-PR) and its 95% CI. Results: Of 1094 persons contacted, 416 were enrolled (response rate: 38%). Long-COVID prevalence was 64% (267/416); 95% CI [59-69%]. The sex ratio (M:F) was 0.72. Age ranged from 1 to 101 years, with a median of 41 years (IQR:31-55 years). The most common symptoms were fatigue (63%), myalgia/arthralgia (33%), and cognitive symptoms (52%). Median duration of long-COVID symptoms was 11 months (IQR: 3-14 months). In multivariate analysis, experiencing acute COVID-19 (a-PR = 1.5; 95% CI [1.0-2.1]), being a woman of childbearing age (a-PR = 1.2; 95% CI [1.0-1.4]) and residing in the central region (a-PR = 1.5; 95% CI [1.1-2.0]) were significantly associated with a higher prevalence of long COVID. Conclusions: Long COVID is prevalent in Tunisia affecting patients with multiple symptoms initially, those residing in the central region and young women. We recommend to enhance healthcare access and medical follow-up both during and after the infection, focusing on identified risk groups. We also recommend to conduct further research to optimize management of long-COVID patients.},
}
@article {pmid41595726,
year = {2026},
author = {Arroyo-Romero, S and Gomez-Sanchez, L and Suarez-Moreno, N and Navarro-Caceres, A and Dominguez-Martin, A and Lugones-Sanchez, C and Gonzalez-Sanchez, S and Gomez-Sanchez, M and Rodriguez-Sanchez, E and Garcia-Ortiz, L and Navarro-Matias, E and Gomez-Marcos, MA},
title = {Clinical Manifestations of Subjects with Long COVID and Their Associations with Drug Use: The BioICOPER Study.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
pmid = {41595726},
issn = {2227-9059},
support = {PI21/00454//Instituto de Salud Carlos III/ ; RD21/0016/0010//Network for Research on Chronicity, Primary Care, and Health Promotion/ ; GRS 2501/B/22//Junta de Castilla y Le&#xf3;n/ ; CB22/06/00035//Centro de Investigaci&#xf3;n Biom&#xe9;dica en Red/ ; },
abstract = {Background/Objectives: Long COVID (LC) is associated with more than 200 symptoms. This study aimed to evaluate the correlation between symptoms clusters and pharmacological treatment in patients with LC and to explore differences by sex. Methods: We conducted a cross-sectional descriptive study including 304 participants diagnosed with LC according to the World Health Organization criteria. Symptoms during the acute phase, at the time of diagnosis of LC, and those persisting across both phases were collected by anamnesis. Symptoms were grouped into six clusters: systemic, neurocognitive, respiratory/cardiovascular, musculoskeletal, neurological/neuromuscular, and psychological/psychiatric. Drug use was assessed through a questionnaire verified by the medical records, including the consumption of cardiovascular drugs, antidepressants/anxiolytics, and anti-inflammatory/analgesics. Results: Patients reported a mean of 5.23 ± 1.10 symptoms in the acute phase, 4.20 ± 1.70 at LC diagnosis, and 3.83 ± 1.80 persisting across both phases. The most consumed pharmacological group was cardiovascular drugs (43.3%), followed by antidepressants/anxiolytics (34.8%). Psychotropic drugs and anti-inflammatory/analgesic drugs showed a positive association with all symptomatic groups (p < 0.05). Cardiovascular drugs showed a positive association with cardiorespiratory (β = 0.19, p < 0.05), neuromuscular (β = 0.11, p < 0.05), and psychological (β = 0.14, p < 0.05) symptoms. Conclusions: Psychotropic and anti-inflammatory/analgesic drugs were positively associated with all symptom clusters, while cardiovascular drugs were associated only with cardiorespiratory, neuromuscular, and psychological symptoms, highlighting the relevance of better characterization of treatment patterns in this population.},
}
@article {pmid41595678,
year = {2026},
author = {Daodu, LP and Raste, Y and Allgrove, JE and Arrigoni, FIF and Kayyali, R},
title = {A Retrospective Observational Study of Pulmonary Impairments in Long COVID Patients.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
pmid = {41595678},
issn = {2227-9059},
support = {KU-RCP10656/"Long COVID -Croydon//Croydon Health Services NHS Trust/ ; },
abstract = {Background/Objective: Pulmonary impairments have been identified as some of the most complex and debilitating post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID. This study identified and characterised the specific forms of pulmonary impairments detected using pulmonary function tests (PFT), chest X-rays (CXR), and computed tomography (CT) scans in patients with long COVID symptoms. Methods: We conducted a single-centre retrospective study to evaluate 60 patients with long COVID who underwent PFT, CXR, and CT scans. Pulmonary function in long COVID patients was assessed using defined thresholds for key test parameters, enabling categorisation into normal, restrictive, obstructive, and mixed lung-function patterns. We applied exact binomial (Clopper-Pearson) 95% confidence intervals to calculate the proportions of patients falling below the defined thresholds. We also assessed the relationships among spirometric indices, lung volumes, and diffusion capacity (DLCO) using scatter plots and corresponding linear regressions. The findings from the CXRs and CT scans were categorised, and their prevalence was calculated. Results: A total of 60 patients with long COVID symptoms (mean age 60 ± 13 years; 57% female) were evaluated. The cohort was ethnically diverse and predominantly non-smokers, with a mean BMI of 32.4 ± 6.3 kg/m[2]. PFT revealed that most patients had preserved spirometry, with mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) above 90% predicted. However, a significant proportion exhibited reductions in lung volumes, with total lung capacity (TLC) decreasing in 35%, and diffusion capacity (DLCO/TLCO) decreasing in 75%. Lung function pattern analysis showed 88% of patients had normal function, while 12% displayed a restrictive pattern; no obstructive or mixed patterns were observed. Radiographic assessment revealed that 58% of chest X-rays were normal, whereas CT scans showed ground-glass opacities (GGO) in 65% of patients and fibrotic changes in 55%, along with findings such as atelectasis, air trapping, and bronchial wall thickening. Conclusions: Spirometry alone is insufficient to detect impairment of gas exchange or underlying histopathological changes in patients with long COVID. Our findings show that, despite normal spirometry results, many patients exhibit significant diffusion impairment, fibrotic alterations, and ground-glass opacities, indicating persistent lung and microvascular damage. These results underscore the importance of comprehensive assessment using multiple diagnostic tools to identify and manage chronic pulmonary dysfunction in long COVID.},
}
@article {pmid41594661,
year = {2026},
author = {Förster, CY and Shityakov, S},
title = {A Possible Role for the Vagus Nerve in Physical and Mental Health.},
journal = {Biomolecules},
volume = {16},
number = {1},
pages = {},
pmid = {41594661},
issn = {2218-273X},
support = {Fo-315/5-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Vagus Nerve/physiology/physiopathology ; *Vagus Nerve Stimulation/methods ; *Mental Health ; COVID-19/therapy ; Animals ; SARS-CoV-2 ; Depression/therapy ; },
abstract = {For decades, researchers have explored the therapeutic potential of the vagus nerve through vagus nerve stimulation (VNS). Initially developed for epilepsy, VNS has since been applied to treat resistant depression, stroke recovery, and inflammatory conditions. Transcutaneous VNS (tVNS) now offers a noninvasive alternative, fueling clinical trials in disorders ranging from rheumatoid arthritis and migraines to long COVID-19. Mechanistic studies suggest that afferent and efferent vagal fibers modulate immune responses, mood regulation, and neurotransmitter systems. The SPARC initiative has accelerated mapping of vagal circuits, enabling more precise approaches to stimulation. Despite progress, the results remain mixed: while some patients experience lasting symptom relief, others respond no better than to placebo. Depression studies, in particular, highlight both the promise and the complexity of VNS, as inflammation, motivation circuits, and gut-brain signaling emerge as key modulators. Next-generation closed-loop devices and circuit-specific targeting may improve efficacy and reduce adverse effects. VNS research thus lies at the intersection of neuromodulation, psychiatry, and immunology-offering hope for hard-to-treat conditions, yet demanding rigorous trials to separate myths from medicine. In this article, we review the current clinical and experimental applications of tVNS, analyze its mixed efficacy across psychiatric, immunological, and neurological disorders, and highlight the mechanistic insights, stimulation parameters, and emerging technologies that may shape next-generation therapies.},
}
@article {pmid41593681,
year = {2026},
author = {Feliz, J and Gonçalves, J and Cabedo, C and Brito, J and Gamas, M and Neves, MI and Soares, H},
title = {Long-term sex differences in symptoms and immune profile in long COVID.},
journal = {Biology of sex differences},
volume = {17},
number = {1},
pages = {32},
pmid = {41593681},
issn = {2042-6410},
support = {Grant Agreement No. GA 101159729//European Union's Horizon Europe research and innovation action through the projects MPS_NOVA/ ; Agreement No. GA 101079264//EVCA Grant/ ; LA/P/0087/2020//Research Unit UID/04462: iNOVA4Health and by Associated Laboratory LS4FUTURE/ ; },
mesh = {Humans ; Female ; Male ; *COVID-19/immunology/complications/physiopathology/epidemiology ; Middle Aged ; Adult ; *Sex Characteristics ; Aged ; SARS-CoV-2 ; Cytokines/blood ; Sex Factors ; },
abstract = {BACKGROUND: Long COVID (LC) is a post-infectious condition affecting millions worldwide, characterized by persistent multisystem symptoms. Females are disproportionately affected, reporting higher symptom burden, particularly neurocognitive and neurosensory complaints. While short-term immunopathology has been described, the long-term clinical course, immune dysregulation, and sex-specific underpinnings remain poorly understood.<br><br>METHODS: We analyzed 34 participants experiencing persisting symptoms from 9&#xa0;months to 5&#xa0;years post-SARS-CoV-2 infection, alongside 26 SARS-CoV-2-infected controls without symptoms. Clinical assessments, symptom inventories, comorbidity analysis, and work capacity evaluation were performed. Immune profiling included flow cytometry of CD4&#x207a; and CD8&#x207a; T cells, NK cells, and B cells, as well as quantification of plasma cytokines, soluble factors, and cytotoxic molecules, analyzed in a sex-disaggregated manner.<br><br>RESULTS: Females with LC exhibited higher symptom burden, particularly persistent fatigue, neurocognitive and neurosensory complaints, which increased with age and tended to increase with disease duration, whereas males showed no clear age- or duration-related patterns. Comorbidities, especially affecting endocrine, metabolic, and circulatory systems, were more frequent in females and aligned with symptom severity. Immune profiling revealed subtle but sex-specific differences: females had reduced CD8&#x207a; T cell cytotoxic profile, lower NKG2D and granzyme K expression, increased sCD40L and sFAS, and decreased perforin, whereas males displayed elevated TNF-&#x3b1;. NK cell function, B cells, and humoral immunity remained largely intact. Over half of participants reported functional impairments affecting work capacity.<br><br>CONCLUSIONS: Even though our cohort is small it suggests that prolonged LC is characterized by sex-specific differences in symptom burden and immune profiles. Reduced cytotoxic CD8&#x207a; T cell profile in females may contribute to viral persistence and neurological symptoms, whereas elevated inflammatory markers in males suggest distinct immune pathways. These findings highlight the need for sex- and duration-specific management strategies, the identification of biomarkers, and the development of personalized therapies targeting specific LC endotypes.},
}
@article {pmid41592666,
year = {2026},
author = {Ngiam, JN and Wee, LE and Lim, JT and Loy, EX and Koh, MCY and Tay, AT and Lou, HX and Kim, P and Chiew, CJ and Young, BE and Vasoo, S and Lye, DCB and Tan, KB},
title = {Early administration of neutralizing monoclonal antibodies and post-acute sequelae of COVID-19.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {164},
number = {},
pages = {108435},
doi = {10.1016/j.ijid.2026.108435},
pmid = {41592666},
issn = {1878-3511},
abstract = {OBJECTIVES: Post-acute sequelae of COVID-19 (PASC) are more common in unvaccinated or immunocompromised individuals. In Singapore, neutralizing monoclonal antibodies (mAbs) were offered early in the disease course to such high-risk patients. We evaluated the impact of early mAb use on the risk of post-acute multi-system complications and symptoms.<br><br>METHODS: Using national COVID-19 registries and healthcare claims data, we conducted a retrospective cohort study including all Singaporeans who were unvaccinated, partially vaccinated, or immunocompromised at the time of SARS-CoV-2 infection between July 2021 and December 2022. Individuals were stratified by receipt of mAbs. Overlap weighting was applied to balance baseline characteristics. Competing risks regression was used to compare outcomes from 31 to 300 days post-infection, adjusted for demographics, vaccination status, and comorbidities.<br><br>RESULTS: Of 19,689 eligible hospitalized individuals, 6.9% received early mAb therapy. While mAb treatment had no significant impact on overall post-acute sequelae (adjusted hazard ratio [aHR] for any sequelae: 1.26 [0.98-1.63]), we observed an increased risk of autoimmune diseases (aHR = 2.20 [1.22-3.97]), particularly systemic lupus erythematosus and rheumatoid arthritis). There was also an elevated risk of deep venous thrombosis (aHR = 1.83 [1.03-3.22]), but this was no longer significant after adjusting for previous healthcare utilization.<br><br>CONCLUSIONS: Early mAb therapy did not significantly alter overall PASC risk but was associated with increased autoimmune complications. These findings may highlight the need for long-term safety monitoring in future mAb trials for SARS-CoV-2.},
}
@article {pmid41591677,
year = {2026},
author = {Zheng, M},
title = {Large-Scale Disease-Wide Association Study Identified Predisposition Links Between Influenza and Cardiovascular Diseases.},
journal = {Cardiovascular toxicology},
volume = {26},
number = {2},
pages = {20},
pmid = {41591677},
issn = {1559-0259},
support = {32100739//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Influenza, Human/epidemiology/diagnosis ; *Cardiovascular Diseases/epidemiology/diagnosis ; Female ; Male ; Middle Aged ; Comorbidity ; Risk Assessment ; Aged ; Adult ; Time Factors ; Risk Factors ; },
abstract = {BACKGROUND: Influenza remains a major global health threat and, akin to "long COVID," has been linked to prolonged multi-organ comorbidities ("long flu"). Cardiovascular diseases (CVDs) are increasingly recognized in the pathogenesis of influenza, yet most prior work emphasizes acute or short-term outcomes and rarely contrasts multiple endpoints over extended horizons.<br><br>METHODS: This study conducted a disease-wide association study (DWAS), assembling individuals with clinically coded influenza without pneumonia (n&#x2009;=&#x2009;5136) and population comparators (n&#x2009;=&#x2009;314,673). Using age- and sex-adjusted Cox models, this analysis screened 106 comorbid endpoints classified by ICD-10/ICD-O-3 and FinnGen disease taxonomy. Associations were evaluated bidirectionally-before influenza (predisposition) and after influenza (subsequent risk)-within prespecified 1-, 5-, and 15-year time windows.<br><br>RESULTS: Influenza showed broad associations spanning circulatory, nervous, endocrine-metabolic, respiratory, musculoskeletal, and other organ systems. CVD endpoints demonstrated the most persistent and directionally consistent DWAS signals. In pre-influenza analyses, greater baseline cardiovascular burden-including heart failure, coronary atherosclerosis, hypertension, major coronary heart disease, atrial fibrillation/flutter, myocardial infarction, stroke, pulmonary embolism, and venous thromboembolism-was associated with higher susceptibility to subsequent influenza. In post-influenza analyses, elevated risks remained for key CVD outcomes-atrial fibrillation/flutter, heart failure, myocardial infarction, and stroke. Non-cardiovascular endpoints (e.g., migraine, sleep apnoea, spinal stenosis, osteoporosis, chronic obstructive pulmonary disease, diabetic nephropathy, and chronic kidney disease) also showed bidirectional associations with influenza, thereby situating CVD within a broader comorbidity and frailty context of influenza.<br><br>CONCLUSIONS: In this population-scale DWAS, CVDs emerged as the most significant comorbidities of influenza. Conceptualizing influenza as a "cardiovascular stress test" supports targeted prevention (e.g., vaccination prioritization) and intensified cardiovascular risk management around influenza seasons. While the biological mechanism remains unclear, this study will motivate future studies integrating biomarkers, cardiovascular imaging, and virologic-immunologic profiling to disentangle causal mechanisms.},
}
@article {pmid41590531,
year = {2026},
author = {Rodrigues, CNDS and Angelotto, FR and Diotto, VL and Cristofoletti, DDM and Araújo, TOP and de Lima, MA and Neto, JC and Prestes, J and Navalta, J and Pereira, GB},
title = {Long COVID Does Not Impair Hemodynamic, Vascular, or Autonomic Responses to Maximal Exercise: Sex-Stratified Study in Young Adults.},
journal = {Journal of personalized medicine},
volume = {16},
number = {1},
pages = {},
pmid = {41590531},
issn = {2075-4426},
support = {23112.031858/2024-30//P&#xf3;s-Gradua&#xe7;&#xe3;o em Fisiologia Cl&#xed;nica do Exerc&#xed;cio do Departamento de Ci&#xea;ncias Fisiol&#xf3;gicas da Universidade Federal de S&#xe3;o Carlos/ ; },
abstract = {Background/Objectives: Long COVID (LC) has been linked to fatigue, exercise intolerance, and autonomic dysfunction, but sex-stratified data on cardiovascular responses to maximal exercise-an essential component of personalized medicine-are scarce. This study aimed to examine hemodynamic, autonomic, and functional responses during and up to 24 h after a cardiopulmonary exercise test (CPET) in young adults with and without Long COVID (LC). Methods: In this cross-sectional study, we assessed 38 physically active adults, who were allocated into four subgroups stratified by clinical condition (LC or control) and biological sex: control-female (CON-F; n = 10), LC-female (LC-F; n = 10), control-male (CON-M; n = 10), and LC-male (LC-M; n = 8). Outcomes included systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), cardiac output (CO), total (TPR) and peripheral vascular resistance (PVR), pulse wave velocity (PWV), augmentation index (AIx@75), and heart rate variability (HF, LF, LF/HF), assessed at rest, peak effort, recovery (1, 3, 5, 10, 30, and 60 min), and through 24 h ambulatory blood pressure monitoring (ABPM) after CPET. Results: SBP increase appropriately during exercise, with higher peaks in males (p < 0.01), and returned to baseline within 5 min across all groups. HR recovery was preserved; however, LC-F showed lower values than CON-F at 3, 5, and 10 min (126 vs. 144 bpm, p = 0.020; 119 vs. 136 bpm, p = 0.020; 94 vs. 109 bpm, p = 0.011), though all groups normalized by 60 min. PWV, AIx@75, TPR and PVR exhibited expected sex-related patterns without LC-related impairments. HRV indices showed transient post-exercise shifts (HF↓, LF↑, LF/HF↑). Ambulatory monitoring confirmed preserved circadian modulation, with normal systolic dipping (11-13%) and no abnormal nocturnal patterns. Conclusions: Young physically active adults with LC showed preserved hemodynamic, autonomic, and vascular responses during and after maximal exercise. These findings contribute to personalized medicine by showing that individualized, sex-stratified cardiovascular assessments reveal no clinically relevant impairments in this population, supporting tailored clinical decision making and exercise prescription.},
}
@article {pmid41590528,
year = {2026},
author = {Selvi, FR and Longhino, D and Lucca, G and Baglivo, I and Zavarella, MA and Laface, C and Bruno, L and Gamberale, S and Fabbroni, L and Rizzi, A and Aruanno, A and Buonagura, R and Curci, M and Buonomo, A and Viola, M and Ianiro, G and Landi, F and Tosato, M and Gasbarrini, A and Caruso, C},
title = {Investigation of Biomarkers in Allergic Patients with Long COVID.},
journal = {Journal of personalized medicine},
volume = {16},
number = {1},
pages = {},
pmid = {41590528},
issn = {2075-4426},
abstract = {Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ[2] = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ[2] = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population.},
}
@article {pmid41589860,
year = {2026},
author = {Al-Delaimy, WK and Bruno, W and Shadyab, A and Saquib N, N and Goveas, JS},
title = {Psychological symptoms predict long coronavirus disease 2019: a prospective analysis from the Women's Health Initiative.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {41589860},
issn = {1530-0374},
abstract = {OBJECTIVE: Those with mental illnesses are likely at higher risk of developing coronavirus disease 2019 (COVID-19), and elderly are disproportionately impacted and as a result suffer more from long COVID. The aim of this analysis was to determine the associations of preexisting depressive and anxiety symptoms with developing COVID-19 positivity, long COVID-19, and compliance with the use of protective measures against contracting COVID-19.<br><br>METHODS: A subsample (n = 18,820) of the Women's Health Initiative study cohort completed longitudinal questionnaires on depressive and anxiety symptoms between 1993 and 2021 and reported on COVID-19 testing and compliance-related questions in 2020 and 2021. Logistic regression analyses were used to prospectively determine associations of a history of mental health symptoms with COVID-related outcomes.<br><br>RESULTS: Reported history of depressive and anxiety symptoms was not associated with COVID-19 positivity. However, higher anxiety scores were associated with higher odds of long COVID (OR = 1.05 [95% CI: 1.03-1.07]). Women with both depressive and anxiety symptoms versus neither symptom had 78% higher odds of long COVID (OR = 1.78 [95% CI: 1.13-2.81 P = 0.001]). The odds of compliance with COVID-19 mitigation measures was significantly lower among women with previous long-term depressive symptoms (OR = 0.67 [95% CI: 0.55-0.82]), with both long-term depressive and anxiety symptoms (OR = 0.75 (95% CI: 0.61-0.93) P < 0.0001), and with higher long-term perceived stress score (OR = 0.94 [95% CI: 0.92-0.97]). However, a higher short-term anxiety score during early COVID was weakly associated with the higher odds of compliance of prevention mitigation measures (OR = 1.03 [95% CI: 1.02-1.03]).<br><br>CONCLUSIONS: Older women with past mental health symptoms may be at higher risk of developing long COVID and having lower compliance with COVID prevention measures.},
}
@article {pmid41588020,
year = {2026},
author = {Abbasi, A and Hansen, N and Palade, J and Paredes, D and Meechoovet, B and Van Keuren-Jensen, K and Pirrotte, P and Stringer, WW},
title = {Serum extracellular vesicle RNA profiles in long COVID: insights from exercise-induced gene modulation.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {3469},
pmid = {41588020},
issn = {2045-2322},
mesh = {Humans ; *Extracellular Vesicles/genetics/metabolism ; *COVID-19/genetics/blood/virology ; Male ; Female ; Middle Aged ; *Exercise/physiology ; SARS-CoV-2/genetics ; Adult ; Pilot Projects ; Gene Expression Regulation ; },
abstract = {The Persistence of SARS-CoV-2 in tissues has been proposed as a driver of prolonged symptoms in long COVID. Pulmonary rehabilitation with exercise training is a well-established intervention for improving symptoms, functional capacity, and inflammation in chronic cardiorespiratory diseases. To investigate whether long COVID is associated with persistent viral or immune-related signals, we analyzed the long RNA profile of circulating extracellular vesicles (EVs) to determine the presence of virus-related transcripts and assess changes in response to exercise training. Fourteen adults with long COVID participated in this single-center pilot clinical trial and completed a 10-week aerobic exercise training program (twenty 1.5 h sessions). Serum-derived EV RNA profiles were analyzed via sequencing at rest (T0) and peak cardiopulmonary exercise testing (T1), before (V2) and after (V24) exercise training. Differentially expressed genes (DEGs) were identified (q < 0.05), and pathway activation analysis was performed. Serum EVs carried diverse RNA species, including protein-coding RNAs, long non-coding RNAs, short non-coding RNAs, and pseudogenes, with no virus-related RNAs detected. No significant DEGs were identified at rest between pre- and post-training, nor in response to acute exercise at pre-training. However, following training, 53 DEGs were found at peak exercise (V24T1) compared to rest (V24T0), including three upregulated genes (ANK3, FTO, FCN1) and 50 downregulated genes (TOP 5: MYL9, NRGN, H2AC6, MAP3K7CL, B2M). These genes were primarily involved in inflammation and metabolism. Pathway analysis revealed significant regulation of 100 pathways at post-training compared to pre training, predominantly inactivated, including pathways involved in inflammation (STAT3 signaling) and metabolism (O-linked glycosylation). Acute exercise and exercise training modulated EV-associated gene expression in long COVID, primarily through transcriptional downregulation. Suppression of inflammation- and immune-related genes post-training highlights potential molecular mechanisms underlying symptom improvement and identifies candidate biomarkers of recovery biology in long COVID. Importantly, while exercise training did not substantially alter EV RNA content at rest, it enhanced the body's ability to mount a dynamic EV-mediated molecular response during exertion, reflecting improved physiological adaptability.Clinical trial registration number: NCT05398692.},
}
@article {pmid41586458,
year = {2026},
author = {Horton, M and Smith, AB and Milne, R and Winch, D and Rayner, C and Halpin, S and O'Connor, R and Rocha Lawrence, R and Greenwood, DC and Bakerly, ND and Evans, R and Kwon, J and Dawes, H and Wood, C and Williams, P and Master, H and Mansoubi, M and De Kock, JH and Mullard, J and Ormerod, M and Mir, G and Petrou, S and O'Connor, DB and Sivan, M and , },
title = {Large-Scale Psychometric Assessment and Validation of the Modified COVID-19 Yorkshire Rehabilitation Scale Patient-Reported Outcome Measure for Long COVID or Post-COVID Syndrome.},
journal = {Journal of medical virology},
volume = {98},
number = {2},
pages = {e70816},
pmid = {41586458},
issn = {1096-9071},
support = {COV-LT2-0016//National Institute for Health and Care Research award/ ; },
mesh = {Humans ; Female ; Male ; *Psychometrics/methods ; *COVID-19/rehabilitation/psychology ; Middle Aged ; *Patient Reported Outcome Measures ; Adult ; Reproducibility of Results ; Aged ; SARS-CoV-2 ; Severity of Illness Index ; Surveys and Questionnaires ; },
abstract = {The C19-YRS was the first condition-specific for long COVID/post-COVID syndrome. Although the original C19-YRS evolved to the modified version (C19-YRSm) based on psychometric evidence, clinical content relevance, as well as feedback from patients and healthcare professionals, it has not been validated through Rasch analysis. The study aim was to psychometrically assess and validate the C19-YRSm using newly collected data from a large-scale, multicenter study (LOCOMOTION). In total, 1278 patients (67% Female; mean age = 48.6, SD 12.7) digitally completed the C19-YRSm. The psychometric properties of the C19-YRSm Symptom Severity (SS) and Functional Disability (FD) subscales were assessed using a Rasch Measurement Theory framework, assessing for individual item model fit, targeting, internal consistency reliability, unidimensionality, local dependency (LD), response category functioning and differential item functioning (DIF) by age group, sex and ethnicity. Rasch analysis revealed robust psychometric properties of both subscales, with each demonstrating unidimensionality, appropriate response category structuring, no floor or ceiling effects, and minimal LD and DIF. Both subscales also displayed good targeting and reliability (SS: Person Separation Index (PSI) = 0.81, Cronbach's α = 0.82; FD: PSI = 0.76, Cronbach's α = 0.81). Although some minor anomalies are apparent, the modifications to the original C19-YRS have strengthened its measurement characteristics and its clinical and conceptual relevance. Trial Registration: NCT05057260, ISRCTN15022307.},
}
@article {pmid41585473,
year = {2026},
author = {Zhang, J and Chen, Y and Zhang, A and Yang, Y and Ma, L and Yu, K and Zhang, W and Ye, X and Zhang, J and Lin, K and Lin, X},
title = {Interpretable machine learning for predicting low-dose methylprednisolone effectiveness in long COVID.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114574},
pmid = {41585473},
issn = {2589-0042},
abstract = {Long COVID is a chronic, multisystem disease with limited response to conventional treatments. While low-dose methylprednisolone has shown effectiveness in some patients, individual responses vary, and accurate predictive tools are lacking. This retrospective study included 330 long COVID patients who received low-dose methylprednisolone treatment across three hospitals. Patients were divided into training (n = 202), test (n = 33), and external validation sets (n = 53, n = 42). Using least absolute shrinkage and selection operator (LASSO) regression, 38 variables were analyzed to develop six machine learning models. The logistic regression (LR) model showed stable performance across all datasets (AUCs: 0.8715, 0.7198, 0.8419, and 0.8676), making it the final model selected. SHapley Additive exPlanations (SHAP) analysis identified seven key variables, which were used to construct a nomogram for predicting treatment efficacy. The LR model and nomogram demonstrated strong predictive performance and clinical interpretability, offering a valuable decision-support tool for individualized treatment of long COVID with low-dose methylprednisolone.},
}
@article {pmid41584202,
year = {2025},
author = {Wen, J and Yuan, L and Zhang, L and Li, L and Chen, J and Zhang, Z and Yan, Y},
title = {Distribution of acute symptoms and long COVID-19 and their association with anxiety and depression 2 years after infection.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1687444},
pmid = {41584202},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; Male ; *Anxiety/epidemiology ; Female ; Retrospective Studies ; Adult ; *Depression/epidemiology ; Cross-Sectional Studies ; Middle Aged ; *Health Personnel/psychology/statistics &amp; numerical data ; Surveys and Questionnaires ; SARS-CoV-2 ; Prevalence ; },
abstract = {BACKGROUND: With the continuing impact of the COVID-19 outbreak, the mental health of infected patients is becoming a widespread concern. However, the relationship between acute-phase symptoms and long COVID-19 symptoms with anxiety and depression 2 years post-infection among healthcare workers remains unclear.<br><br>OBJECTIVE: The aim of this study was to investigate the relationship between acute phase symptoms and long COVID-19 symptoms of novel COVID-19 infection and anxiety and depression 2&#x202f;years after infection.<br><br>METHODS: Using a retrospective cohort study and cross-sectional design, this study collected data on acute-phase symptoms, long COVID-19 symptoms, and their levels of anxiety and depression from 1,038 COVID-19 patients by questionnaire. We explored their relationship through logistic regression. We also used RCS curves to explore the nonlinear relationship between acute phase symptoms and long COVID-19 symptoms and anxiety and depression 2&#x202f;years after infection.<br><br>RESULTS: The aim of this study was to investigate the prevalence of common symptoms of long COVID-19 in a sample of medical staff with COVID-19 infection. The study also aimed to explore the relationship between long COVID-19 symptoms and mental health status. The results showed that among patients who tested positive for COVID-19 by December 2022, approximately 34.0% exhibited overall long COVID-19 symptoms 2&#x202f;years after infection. Decreased concentration and memory were the most common long COVID-19 symptoms, accounting for 12.5% of all COVID-19 patients. In this study, we also explored the relationship between acute-phase symptoms or long COVID-19 symptoms and anxiety and depression 2&#x202f;years after infection. The findings showed that both acute phase symptoms as well as long COVID-19 symptoms were significantly associated with levels of anxiety and depression 2&#x202f;years after infection. We also found a nonlinear relationship between the number of long COVID-19 symptoms and anxiety and depression.<br><br>CONCLUSION: In summary, the positive correlation between the acute phase of COVID-19 infection and the impact of long COVID-19 symptoms on mental health suggests that focusing on the mental health of patients recovering from the epidemic is critical. Effective psychological interventions should be part of the comprehensive treatment of long COVID-19 to help patients improve their mental health while recovering physically.},
}
@article {pmid41582616,
year = {2026},
author = {Tmava, A and Burstein, EM},
title = {A call for a critical medical anthropology of the COVID-19 pandemic.},
journal = {Anthropology &amp; medicine},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/13648470.2025.2604010},
pmid = {41582616},
issn = {1469-2910},
abstract = {This paper is a call for a renewed critical medical anthropology (CMA) of the COVID-19 pandemic, one that attends not only to the pandemic's acute phase but also to its enduring afterlife. We argue that COVID-19 persists as a structuring condition that continues to impact individual experiences as well as domestic and global politics and culture. We introduce the concept of 'narrative compression' to describe how public and institutional discourses have foreclosed space for the ongoing suffering of individuals with long COVID and others marginalized by pandemic legacies. By tracing how closure is epistemically and politically produced, this paper reframes COVID-19 as an ambient and persistent crisis. We advocate for an anthropological approach that remains with the pandemic to diagnose its transformations and imagine more accountable health futures.},
}
@article {pmid41581925,
year = {2026},
author = {Keat, SBK and Khatri, P and Ali, YM and Arachchilage, CH and Demopulos, G and Baillie, K and Miners, KL and Ladell, K and Jones, SA and Davies, HE and Price, DA and Zelek, WM and Morgan, BP and Schwaeble, WJ and Lynch, NJ},
title = {Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.},
journal = {Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imm.70110},
pmid = {41581925},
issn = {1365-2567},
support = {//UK Dementia Research Institute/ ; COV0170//National Institute for Health and Care Research/ ; COV-LT2-0041//National Institute for Health and Care Research/ ; //Omeros Corporation/ ; Balvi B43//PolyBio Research Foundation/ ; 520488//Race against Dementia Alzheimer's Research/ ; },
abstract = {Long COVID affects a substantial proportion of survivors of acute infection with severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), who suffer a variety of symptoms that limit their quality of life and economic activity. Although the aetiology of long COVID is obscure, it appears to be a chronic inflammatory condition. Complement dysregulation is a prevalent feature of long COVID. Specifically, markers of classical, alternative, and terminal pathway activation are often elevated in patients with this condition. Here, we used a sensitive assay for mannan-binding lectin-associated serine protease-2 (MASP-2)/C1Inh complexes to analyse lectin pathway activation in a previously characterised cohort of patients with long COVID (n = 159) and healthy convalescent individuals with no persistent symptoms after infection with SARS-CoV-2 (n = 76). The data were combined with those from the most predictive complement analytes identified previously to delineate potential biomarkers of long COVID. MASP-2/C1Inh complexes were significantly elevated in patients with long COVID (p = 0.0003). Generalised linear modelling further identified an optimal set of four markers, namely iC3b (alternative pathway), TCC (terminal pathway), MASP-2/C1Inh (lectin pathway), and the complement regulator properdin, which had a receiver operating characteristic predictive power of 0.796 (95% confidence interval = 0.664-0.905). Combinations of the classical pathway markers C4, C1q, and C1s/C1Inh were poorly predictive of long COVID. These findings demonstrate that activation of the lectin complement pathway, which occurs upstream of the alternative and terminal pathways and can be inhibited therapeutically, is a salient feature of long COVID.},
}
@article {pmid41581648,
year = {2026},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Natural history of self-reported symptoms following SARS-CoV-2 infection: A target trial emulation in a prospective community-recruited cohort.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {164},
number = {},
pages = {108422},
doi = {10.1016/j.ijid.2026.108422},
pmid = {41581648},
issn = {1878-3511},
abstract = {BACKGROUND: Using a prospective, community-recruited cohort with data on background symptom prevalence and repeated longitudinal symptom assessments, we estimated postinfection risks of long Coronavirus disease (COVID) symptoms compared with contemporaneous uninfected controls.<br><br>METHODS: We analyzed the CHASING COVID Cohort, a US longitudinal study with surveys and serology (March 2020-December 2023). Infection status (January 2021-December 2022) was determined from self-reported PCR/antigen results, serology, or Council of State and Territorial Epidemiologists probable criteria. We emulated 24 monthly target trials comparing individuals newly infected at time zero with those remaining uninfected. Outcomes were new-onset long-COVID symptoms not reported preinfection, assessed overall and within three clusters (neurological, autonomic, and exercise intolerance) at 4-8 and 9-12 months postinfection. Inverse probability of treatment and censoring weights adjusted for confounding and informative loss to follow-up.<br><br>RESULTS: The analysis included 1055 infected and 52,310 uninfected person-trials. At 4-8 months, the adjusted risk of any long-COVID symptom was 22.6% (95% CI, 20.5-24.8) among infected vs 11.3% (11.1-11.5) among uninfected (adjusted risk difference [aRD], 11.3% [9.2-13.5]; adjusted risk ratio [aRR], 2.01 [1.81-2.20]). At 9-12 months, risks were 19.2% (17.0-21.3) vs 12.4% (12.2-12.7) (aRD, 6.7% [4.6-8.9]; aRR, 1.54 [1.37-1.72]). Across all three clusters, infected participants had consistently higher risks at both intervals.<br><br>CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was associated with an elevated risk of new-onset long-COVID symptoms persisting up to 12 months. Using a national community-recruited cohort, contemporaneous uninfected controls, and target-trial emulation clarifies the burden attributable to infection and supports ongoing surveillance and targeted prevention and care.},
}
@article {pmid41580734,
year = {2026},
author = {Fang, H and Wang, Q},
title = {The silent epidemic within the pandemic: pathophysiology and prediction of post-COVID-19 diabetes.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {266},
pmid = {41580734},
issn = {1479-5876},
abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has presented extraordinary challenges to global public health, with impacts reaching beyond acute respiratory manifestations to include long-term metabolic disturbances. Emerging evidence indicates a significant link between SARS-CoV-2 infection and the onset of diabetes mellitus, establishing this condition as a major element of the post-acute sequelae of COVID-19, often referred to as Long COVID.<br><br>MAIN BODY: This review synthesizes epidemiological findings that demonstrate a elevated incidence of new-onset diabetes following COVID-19, particularly among certain high-risk demographic groups. We examine the molecular mechanisms underpinning this association, such as viral entry into pancreatic &#x3b2;-cells via ACE2 receptors, systemic inflammation leading to insulin resistance, and the potential diabetogenic effects of glucocorticoids used in COVID-19 treatment. Furthermore, this review outlines biomarker profiles that distinguish COVID-19-associated diabetes from traditional type 2 diabetes, underscoring important pathophysiological differences. Additionally, we evaluate advances and ongoing challenges in developing predictive risk models that combine clinical and molecular data to identify individuals at elevated risk for post-COVID diabetes.<br><br>CONCLUSIONS: By integrating multidisciplinary evidence, this comprehensive narrative review aims to guide future research and shape clinical approaches for early detection, prevention, and management of diabetes following COVID-19, thereby confronting a latent health crisis emerging within the broader pandemic context.},
}
@article {pmid41580699,
year = {2026},
author = {Mou, K and Gao, Y and Zhang, Y and Man, S and Chen, Q and Xu, H and Chen, Y and Zhang, M},
title = {Long-term retinal dysfunction following COVID-19 infection: a one-year prospective observational study.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {96},
pmid = {41580699},
issn = {1471-2415},
support = {2023HXFH043//1&#xb7;3&#xb7;5 project for disciplines of excellence-Clinical Research Fund, West China Hospital, Sichuan University/ ; },
abstract = {BACKGROUND: COVID-19, caused by SARS-CoV-2, may lead to long-term retinal changes. Visual symptoms and retinal alterations have been reported in Long COVID; however, the available evidence remains limited. Swept-source OCT (SS-OCT) and OCT angiography (SS-OCTA) enable non-invasive evaluation of retinal structure and microvasculature. This study aimed to assess retinal alterations before and one year after COVID-19 using SS-OCT and SS-OCTA in a longitudinal design.<br><br>METHODS: This prospective longitudinal study was conducted at West China Hospital, Sichuan University. All enrolled participants underwent SS-OCT and SS-OCTA before infection, and at 1 month, and 1 year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Retinal structural and microvascular alterations were quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, including the thickness of peripheral retinal nerve fiber layer (pRNFL), ganglion cell inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer retina, and the vessel density (VD) of superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). The foveal avascular zone (FAZ) area was measured in the inner retinal layer.<br><br>RESULTS: A total of 44 eyes from 22 participants were analyzed (mean age: 30.59&#x2009;&#xb1;&#x2009;9.36 years; 17 females and 5 males). Significant reduction in thickness of pRNFL, GCIPL, and outer retina, increased thickness of INL, decreased VD of SVP, and increased VD of ICP and DCP were observed in participants one month after COVID-19 infection (All P&#x2009;<&#x2009;0.05), which remained persistently altered one year after COVID-19 infection (All P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: These findings indicate long-term retinal dysfunction following COVID-19 infection, highlighting the importance of ongoing ophthalmic monitoring. Non-invasive SS-OCT and SS-OCTA could offer valuable tools for detecting and managing retinal alterations associated with long COVID in the post-pandemic era.},
}
@article {pmid41580590,
year = {2026},
author = {Mischke, M and Zaehle, T},
title = {Modulating subjective and objective cognitive state fatigue in long COVID with repetitive anodal tDCS: results from a double-blinded randomized controlled trial.},
journal = {BMC neuroscience},
volume = {27},
number = {1},
pages = {6},
pmid = {41580590},
issn = {1471-2202},
mesh = {Humans ; Double-Blind Method ; *Transcranial Direct Current Stimulation/methods ; Male ; Female ; Adult ; *COVID-19/complications/psychology ; *Fatigue/therapy/etiology/physiopathology ; *Dorsolateral Prefrontal Cortex/physiopathology ; Middle Aged ; Cognition/physiology ; Young Adult ; *Mental Fatigue/therapy/physiopathology/etiology ; },
abstract = {BACKGROUND: Cognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) has been proposed as a promising approach to modulate fatigue-related neural networks. To comprehensively assess cognitive fatigue, the integration of subjective and objective behavioral and electrophysiological measures of induced state fatigue is essential.<br><br>METHODS: This double-blind, randomized, sham-controlled study investigated the effects of four consecutive daily sessions of 30-minute anodal tDCS over the left dlPFC on subjective and objective markers of cognitive state fatigue in individuals with long COVID. The present paper focuses on secondary outcomes, including subjective state fatigue ratings via visual analogue scales, behavioral performance indices, and electrophysiological markers such as temporal alterations of frontal theta and occipital alpha activity as well as p50 sensory gating.<br><br>RESULTS: Forty participants received either verum or sham tDCS while completing a gamified adaptive Go/No-Go task. Before and after the stimulation period, cognitive state fatigue was reliably induced using the AX-Continuous Performance Task (AX-CPT). Although tDCS did not significantly affect subjective state-fatigue ratings or behavioral performance, our findings indicate that verum stimulation may stabilize fatigue-related changes in occipital alpha power. No immediate stimulation-related improvements were found in the Go/No-Go task.<br><br>CONCLUSIONS: These findings indicate that while tDCS may modulate neurophysiological correlates of cognitive state fatigue, its impact on subjective experience and behavioral performance remain limited under the current protocol. These results, however, underscore the importance of including neurophysiological endpoints in intervention research and highlight the need for developing more robust and individualized stimulation protocols. Future studies should consider extended stimulation regimens, alternative task paradigms, and more sensitive behavioral measures to further elucidate the neuromodulatory potential of tDCS in long COVID-related cognitive fatigue.<br><br>TRIAL REGISTRATION: drks.de Identifier: DRKS00031294, date of registration: 17.02.2023.},
}
@article {pmid41578033,
year = {2026},
author = {Aid, M and Boero-Teyssier, V and McMahan, K and Dang, R and Doyle, M and Belabbaci, N and Borducchi, E and Collier, AY and Mullington, J and Barouch, DH},
title = {Author Correction: Long COVID involves activation of proinflammatory and immune exhaustion pathways.},
journal = {Nature immunology},
volume = {27},
number = {3},
pages = {637},
doi = {10.1038/s41590-026-02438-1},
pmid = {41578033},
issn = {1529-2916},
}
@article {pmid41577420,
year = {2026},
author = {Schuster, AM and Alwan, NA and Callard, F and Chen, EYH and Gilbody, S and Graham, BM and Hatch, SL and Jones, E and Jordan, A and Knapp, M and López-Jaramillo, C and Nakimuli-Mpungu, E and Pathare, S and Ressler, KJ and Wessely, S and White, LA and , and Jones, PB},
title = {The implications of the COVID-19 pandemic for clinical mental health care.},
journal = {The lancet. Psychiatry},
volume = {13},
number = {2},
pages = {140-161},
doi = {10.1016/S2215-0366(25)00247-0},
pmid = {41577420},
issn = {2215-0374},
mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Mental Health Services/organization &amp; administration ; *Mental Disorders/therapy/epidemiology ; Pandemics ; SARS-CoV-2 ; Mental Health ; },
abstract = {A Position Paper published in The Lancet Psychiatry in 2020 suggested an agenda for research about the effects of the COVID-19 pandemic on mental health, following which an interdisciplinary Lancet Psychiatry standing commission was established in 2022 to examine the emerging evidence and refine recommendations for more research. In this first Series paper from the standing commission, we focus on changes in the delivery of clinical mental health care during the COVID-19 pandemic. The second paper in the Series focuses on public mental health and policy perspectives, and the third will address neuropsychiatric consequences of infection by SARS-CoV-2. Evidence from high-quality longitudinal studies with pre-pandemic baseline data, controlled intervention trials, or systematic reviews took time to accrue. During the early months of the COVID-19 pandemic, symptoms of anxiety and depression became more prevalent, and many mental health services were compromised by pandemic-related factors; however, whether the COVID-19 pandemic accelerated pre-existing long-term trends of increasing incidence of mental health disorders, especially in children and adolescents, is unclear. Little research has been done in low-income and middle-income countries, or regarding post-COVID-19 condition (also known as long COVID), which emerged as a multisystem condition with mental health implications. Vulnerable populations, including socioeconomically disadvantaged and minoritised groups, faced disproportionate mental health impacts and limited access to care during the COVID-19 pandemic, reflecting systemic, pre-pandemic inequalities. Bold implementation of existing evidence-based mental health support for vulnerable communities, ambitious trials of novel interventions, and systematic pooling of rapidly accumulating evidence about best healh care should be priorities in future pandemics.},
}
@article {pmid41576003,
year = {2026},
author = {Novak, P and Systrom, DM and Witte, A and Marciano, SP and Felsenstein, D and Milunsky, JM and Milunsky, A and Krier, J and Fishman, MC},
title = {Shared autonomic phenotype of long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0341278},
pmid = {41576003},
issn = {1932-6203},
mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology ; Female ; *COVID-19/physiopathology/complications ; Male ; Middle Aged ; Adult ; Retrospective Studies ; *Autonomic Nervous System/physiopathology ; Phenotype ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are relatively common and disabling multisystem disorders that share overlapping features, including post-infectious onset and similar clinical manifestations such as brain fog, fatigue, muscle pain, and dysautonomia with orthostatic intolerance. These similarities suggest that Long COVID and ME/CFS may share common pathophysiological mechanisms, though the underlying mechanisms remain poorly understood, partly due to the difficulty in quantifying many of the symptoms.<br><br>MATERIALS AND METHODS: This retrospective study evaluated Long COVID and pre-COVID ME/CFS patients who completed autonomic testing between 2018 and 2023 at the Brigham and Women's Faulkner Hospital Autonomic Laboratory. The evaluations included autonomic tests (Valsalva maneuver, deep breathing, tilt-table test, and sudomotor function) with capnography and transcranial Doppler monitoring of cerebral blood flow velocity (CBFv) in the middle cerebral artery, neuropathic assessment through skin biopsies for small fiber neuropathy (SFN), invasive cardiopulmonary exercise testing (ICPET), and laboratory analyses covering metabolic, inflammatory, autoimmune, and hormonal profiles.<br><br>RESULTS: A total of 143 Long COVID and 170 ME/CFS patients were analyzed and compared to 73 healthy controls and 290 patients with hypermobile Ehlers-Danlos syndrome (hEDS). Tests revealed extensive similarities between Long COVID and ME/CFS, including reduced orthostatic CBFv (92%/88% in Long COVID/ME/CFS), mild-to-moderate widespread autonomic failure (95%/89%), presence of SFN (67%/53%), postural tachycardia syndrome (POTS) (22%/19%), neurogenic orthostatic hypotension (15%/15%) and preload failure (96%/92%, assessed in 25/66 Long COVID/ME/CFS). Patients with hEDS exhibited more severe peripheral neurodegeneration compared to the other groups. Laboratory tests did not distinguish between the conditions.<br><br>CONCLUSION: Both Long COVID and ME/CFS demonstrate dysregulation in cerebrovascular blood flow, autonomic reflexes, and small fiber neuropathy, suggesting that these conditions may share a common underlying pathophysiology. However, differing distributions of findings in patients with hEDS raise the question of whether these conditions represent distinct but overlapping syndromes or reflect a shared underlying pathway. Further research is required to clarify the relationship between these conditions and the potential underlying pathophysiological mechanisms.},
}
@article {pmid41573552,
year = {2025},
author = {Perico, L and Bovio, A and Tomasoni, S and Trionfini, P and Cerullo, D and Corna, D and Pezzotta, A and Locatelli, M and Alberti, M and Benigni, A and Remuzzi, G},
title = {Acetylsalicylic acid disrupts SARS-CoV-2 spike protein glycosylation and selectively impairs binding to ACE2.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1706997},
pmid = {41573552},
issn = {1664-3224},
mesh = {*Spike Glycoprotein, Coronavirus/metabolism ; Animals ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; Glycosylation/drug effects ; *SARS-CoV-2/drug effects/metabolism ; *Aspirin/pharmacology ; Humans ; Vero Cells ; Mice ; Chlorocebus aethiops ; COVID-19/metabolism/virology ; Mice, Transgenic ; Protein Binding/drug effects ; *COVID-19 Drug Treatment ; },
abstract = {Preclinical and clinical evidence suggested the potential benefits of treatment with acetylsalicylic acid (ASA) in mitigating COVID-19 severity. While available studies largely focused on the intracellular pathways through which ASA impairs viral replication or dampens host immunoresponse stimulated by SARS-CoV-2, whether ASA directly affects the interaction between the viral spike protein and its cellular receptor angiotensin converting enzyme 2 (ACE2) remains unexplored. This question is clinically relevant, as circulating spike S1 has been shown to persist in patients with acute and long COVID-19, where its interaction with the broadly expressed ACE2 drives systemic manifestations and tissue damage. Here, we demonstrate that pre-incubation of the SARS-CoV-2 spike subunit 1 (S1) with ASA dose-dependently impaired ACE2 binding on Vero cells. The functional relevance of this finding was confirmed in transgenic mice with human ACE2, in which intratracheal administration of ASA-treated S1 markedly reduced lung injury, fibrosis, and inflammation compared to untreated S1. Glycoproteomic profiling revealed that ASA altered the glycosylation landscape of S1, particularly N-glycosylation at N61 and O-glycosylation at S325. Site-directed mutagenesis of these two residues confirmed the critical role of their glycosylation in S1-ACE2 binding in vitro. Consistently, the glycosylation-insensitive S1 had limited effect in inducing lung injury, fibrosis, and inflammation in transgenic mice compared to WT S1, phenocopying the protective effects of ASA. These findings unveil a previously unrecognized antiviral activity of ASA, providing a molecular rationale for its repurposing as a low-cost, readily available intervention to prevent the progression from mild to severe COVID-19.},
}
@article {pmid41573029,
year = {2025},
author = {Dirwanto, L and Ali, D and Japaries, W and Agussalim, WS},
title = {Effectiveness of Transcutaneous Electrical Acupoint Stimulation in the Treatment of Post-COVID Severe Dyspnea: A Case Report.},
journal = {Medical acupuncture},
volume = {37},
number = {5},
pages = {408-411},
pmid = {41573029},
issn = {1933-6586},
abstract = {INTRODUCTION: Long COVID, or post-COVID syndrome, refers to signs, symptoms, and conditions that persist or emerge following an acute coronavirus disease (COVID-19) infection. The most frequent symptoms are fatigue and dyspnea, with approximately 10-20% of patients recovering from COVID-19. Currently, there are no specific medical recommendations, except for symptomatic treatment.<br><br>OBJECTIVE: To evaluate the use of transcutaneous electrical acupoint stimulation (TEAS) for the treatment of post-COVID severe dyspnea.<br><br>METHODOLOGY: This is a case report of successful treatment using TEAS in a patient with severe dyspnea after recovery from COVID-19.<br><br>RESULTS: A female adult patient experienced progressive dyspnea after recovering from COVID-19 a year prior. One session of TEAS successfully relieved severe dyspnea. No adverse effects or recurrence of dyspnea were reported at the 6-month follow-up.<br><br>CONCLUSION: TEAS is a safe, simple, and effective treatment for overcoming post-COVID severe dyspnea.},
}
@article {pmid41570188,
year = {2025},
author = {Ford, ND and Simeone, RM and Pratt, C and Saydah, S},
title = {Functional Limitations and Illness-Related Absenteeism among School-Aged Children with and without Long COVID, United States, 2022-2023.},
journal = {Emerging infectious diseases},
volume = {31},
number = {14},
pages = {11-19},
pmid = {41570188},
issn = {1080-6059},
mesh = {Humans ; Child ; *Absenteeism ; *COVID-19/epidemiology ; Adolescent ; Male ; Female ; United States/epidemiology ; Cross-Sectional Studies ; Child, Preschool ; SARS-CoV-2 ; Schools ; Pandemics ; },
abstract = {We examined functional limitations and illness-related chronic absenteeism (i.e., missing >18 days of school for health reasons) in a cross-sectional nationally representative sample of 11,057 US children 5-17 years of age who ever or never had long COVID (i.e., symptoms lasting >3 months after COVID-19 illness). Among 4,587 children with prior COVID-19, we estimated whether long COVID was associated with increased illness-related chronic absenteeism by using logistic regression. Our analysis showed that ≈1.4% of school-aged children had long COVID at some point. Among children with prior COVID-19, those who had long COVID at some point more frequently reported functional limitations, such as difficulty with memory, than those who did not have long COVID (18.3% vs. 8.6%). Having long COVID was associated with higher odds of illness-related chronic absenteeism. Children who had long COVID could experience functional limitations and absenteeism. School accommodations might be an option to improve functional limitations.},
}
@article {pmid41570186,
year = {2025},
author = {Pratt, CQ and Dalton, AF and Koumans, EH and Agedew, A and Coronado, F and Lundeen, EA and Woodruff, RC and Block, JP and Weiner, M and Cowell, L and Arnold, JD and Saydah, S and , },
title = {Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection.},
journal = {Emerging infectious diseases},
volume = {31},
number = {14},
pages = {3-10},
pmid = {41570186},
issn = {1080-6059},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Stroke/epidemiology/etiology ; Male ; *Thrombosis/epidemiology/etiology ; Female ; *Respiratory Tract Infections/complications/epidemiology ; Middle Aged ; Aged ; Incidence ; SARS-CoV-2 ; Adult ; Risk Factors ; Hospitalization ; Aged, 80 and over ; },
abstract = {Previous studies have documented an increased risk for thrombotic events 30 days after COVID-19 infection, but less is known about this risk beyond 30 days or compared with risk after other infectious acute respiratory illnesses (ARIs). By using PCORnet data from April 1, 2022-April 30, 2023, we compared the incidences of thrombotic events in the year after COVID-19 illness with other ARI diagnoses in hospitalized and nonhospitalized patients. Overall, the risk for any thrombotic event was higher among patients with COVID-19 compared with patients with other ARIs (incidence ratio 1.63; p<0.05). Nonhospitalized patients with COVID-19 had a 73% increased risk for a thrombotic event in the year after acute illness compared with nonhospitalized patients with ARI (p<0.05). The increased risk for thrombotic events in the year after COVID-19 emphasizes the need for stroke awareness for patients and healthcare professionals.},
}
@article {pmid41570177,
year = {2025},
author = {Fiore, AE},
title = {Progress Toward Understanding Infection-Associated Chronic Conditions and Illnesses.},
journal = {Emerging infectious diseases},
volume = {31},
number = {14},
pages = {1-2},
pmid = {41570177},
issn = {1080-6059},
}
@article {pmid41569391,
year = {2026},
author = {Raymond, KF and Hodge, T and St Jean, B and Liu, BF},
title = {Barriers to Long COVID Care in the U.S.: An Application of Levesque et al.'s Access Framework.},
journal = {Health care analysis : HCA : journal of health philosophy and policy},
volume = {},
number = {},
pages = {},
pmid = {41569391},
issn = {1573-3394},
support = {Pandemic Readiness Initiative//University of Maryland/ ; Pandemic Readiness Initiative//University of Maryland/ ; },
abstract = {Long COVID is a condition that arose during the COVID-19 pandemic in individuals who developed the multi-system chronic condition after a COVID-19 infection. During the pandemic in the United States (U.S.), these "COVID long-haulers" navigated a complex and overburdened health care system in pursuit of diagnoses and treatments. This qualitative secondary analysis used the 2013 Levesque et al. Conceptual Model of Healthcare Access to examine multidimensional health care access issues faced by 29 COVID long-haulers in the U.S. Our analysis showed that long-haulers faced complementary issues from both individual and health systems perspectives related to the inability to get diagnoses or treatments, long waiting times for providers and difficulty reaching services, underinformed providers and biased interpersonal experiences, and struggles with the financial costs of treating the condition, which impacted care decisions. Interviewees also described relying on alternative medicine to provide symptom relief. Overall, this study extends international research by offering a comprehensive examination of Long COVID health care access issues in the U.S. and identifying specific insights related to health care access that made obtaining Long COVID care difficult, such as the mismatch between individual expectations of what health care should look like and how it actually operates. Our use of the full Conceptual Model of Healthcare Access provides new insights into the overlap across layers of access issues and offers suggestions for how public health and clinical health practitioners can collaborate to meet the needs of vulnerable populations such as these in future health emergencies.},
}
@article {pmid41568000,
year = {2025},
author = {Camici, M and Franco, M and Talamanca, L and Petino, M and Paulicelli, J and Scarnecchia, L and Ciavarella, L and Orzilli, T and Balducelli, F and Mazzotta, V and Mastrorosa, I and Cimini, E and Tartaglia, E and Notari, S and Maggi, F and Girardi, E and Baldelli, R and Zuppi, P and Antinori, A},
title = {Salivary cortisol in long COVID: a marker of broader stress system and circadian rhythm dysregulation.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1690698},
pmid = {41568000},
issn = {2235-2988},
mesh = {Humans ; *Hydrocortisone/analysis/metabolism ; *Saliva/chemistry ; Female ; *COVID-19/metabolism/physiopathology/complications ; Middle Aged ; Male ; *Circadian Rhythm/physiology ; Prospective Studies ; Case-Control Studies ; Aged ; Hypothalamo-Hypophyseal System/physiopathology ; Pituitary-Adrenal System/physiopathology ; SARS-CoV-2 ; Biomarkers/analysis ; Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long COVID (LC) has been associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, although findings from blood cortisol measurements remain inconsistent. We hypothesized that LC patients exhibit a disrupted diurnal cortisol rhythm and that salivary cortisol (SC) profiling may provide a more accurate assessment of HPA activity.<br><br>METHODS: This prospective, single-center, case-control study was conducted at a Long COVID clinic in Rome between February 2023 and March 2024 and included 96 participants evaluated at least 28 days after confirmed SARS-CoV-2 infection. LC was defined as one or more new or persistent symptoms and classified as severe when four or more of the following were present: fatigue, cognitive impairment, exercise intolerance, dyspnea, arthralgia, or dysautonomia. SC was measured at 8:00 AM, 3:00 PM, and 11:00 PM.<br><br>RESULTS: The cohort (mean age 58.1 &#xb1; 14.8 years; 60% female; all White) included 83 LC patients (80% moderate, 20% severe) and 13 asymptomatic post-COVID (APC) individuals. Compared with healthy controls, both LC and APC groups showed reduced morning SC (p<0.01), flattened diurnal variation, and elevated evening SC, indicating loss of the normal morning peak and nocturnal decline. Blood cortisol levels did not differ among groups, but LC patients had higher ACTH than APC (26 pg/mL vs 13 pg/mL; p<0.01), suggesting compensatory HPA activation. One LC patient (1.2%) was diagnosed with adrenal insufficiency.<br><br>DISCUSSION: These exploratory findings suggest a disrupted circadian cortisol rhythm in individuals after COVID-19, with altered HPA axis dynamics that may be associated with disease severity.},
}
@article {pmid41566432,
year = {2026},
author = {Gottlieb, M and Yu, H and Chen, J and Spatz, ES and Gentile, NL and Geyer, RE and Santangelo, M and Malicki, C and Gatling, K and O'Laughlin, KN and Stephens, KA and Elmore, JG and Wisk, LE and L'Hommedieu, M and Rodriguez, RM and Montoy, JCC and Wang, RC and Rising, KL and Kean, E and Dyal, JW and Hill, MJ and Venkatesh, AK and Weinstein, RA and , },
title = {Obesity and Long COVID: intersecting epidemics?.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {626},
pmid = {41566432},
issn = {1471-2458},
support = {75D30120C08008/CC/CDC HHS/United States ; 75D30120C08008/CC/CDC HHS/United States ; },
abstract = {BACKGROUND: Obesity affects over 10% of the world population and has significant public health implications. With rising recognition of the long-term effects of Long COVID (LC) coupled with new agents to facilitate weight loss, it is critical to understand the influence of obesity on LC. This study assessed the association of obesity with rates of LC and degree of LC-related mental and physical health outcomes among participants up to three years after initial infection.<br><br>METHODS: This was a cross-sectional, multisite study of participants with SARS-CoV-2 infection from 12/11/2020&#x2013;8/29/2022, with data collected through 4/2/2024. Surveys included validated tools for physical and mental health. Data were analyzed by self-reported new obesity (follow-up only), persistent obesity (baseline and follow-up), or no obesity.<br><br>RESULTS: Of 3,663 participants, 547 (14.9%) had new obesity and 805 (21.9%) had persistent obesity. Compared with persons without obesity, LC was significantly more common among those with new (39.7% vs 22.8%; aOR: 1.9, 95% CI 1.5&#x2013;2.4) or persistent obesity (39.1% vs 22.8%; aOR: 1.7, 95% CI 1.4&#x2013;2.1). Regardless of chronicity and current LC status, obesity was associated with lower (worse) scores for PROMIS Physical (mean differences: 2.7&#x2013;4.0) and Mental Health (mean differences: 1.7&#x2013;3.6) function, worse moderate-to-severe fatigue (aOR: 1.3&#x2013;2.1), worse dyspnea (aOR: 1.9&#x2013;3.7), worse loneliness (aOR: 1.3&#x2013;1.6), and insufficient activity (aOR for SNAP&#x2009;&#x2264;&#x2009;4: 1.6&#x2013;2.8; aOR for EVS&#x2009;&#x2264;&#x2009;150&#xa0;min/week: 2.0&#x2013;3.1).<br><br>CONCLUSIONS: Participants with obesity had higher rates of LC and worse physical and mental health outcomes, regardless of LC status. These findings raise key questions about obesity interventions to treat LC and a possible role for obesity management before the next pandemic.<br><br>TRIAL REGISTRATION: NCT04610515<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-26134-1.},
}
@article {pmid41566340,
year = {2026},
author = {Virga, F and Taverna, D and Ferrero, G and Leclercq, M and El Hachem, N and Godoy-Tena, G and Jacobs, C and Tarallo, S and Pardini, B and Naccarati, A and Wauters, J and Lauwers, HM and Wauters, E and Close, P and Orso, F and Mazzone, M},
title = {Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {247},
pmid = {41566340},
issn = {1479-5876},
abstract = {BACKGROUND: The progression to critical COVID-19 arises predominantly from a dysregulated host immune response although the underlying regulatory mechanisms still remain partially elusive. This limits a prompt prediction of the disease progression, reduces the therapeutic options and restrains our understanding of “long COVID”.<br><br>METHODS: Here, we analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) collected from COVID-19 patients experiencing different degrees of the disease (mild and critical), and control patients enrolled in the clinical trial COntAGIouS as well as independent bulk RNA-seq, single-cell RNA-seq and proteomic datasets.<br><br>RESULTS: In critical COVID-19 patients, the integrative analysis of transcriptomic data revealed an altered regulatory network involving microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and coding genes that control mRNA translation-related genes, epigenetics, and metabolism. In parallel, we observed an upregulation of tRNA aminoacylation genes in critical COVID-19 patients by the analysis of either bulk or single-cell RNA-seq data from publicly available independent cohorts. Additionally, we found increased expression of coding genes enriched for the cognate amino acids (glycine, alanine, isoleucine and tyrosine), all related to protein localization, post-translational modifications, and cell metabolism in our cohort. Similar alterations in amino acid frequency were found in an independent proteomic dataset.<br><br>CONCLUSIONS: Collectively, our findings indicate a broad perturbation of the gene expression landscape that characterizes the aberrant host immune response in critical COVID-19 patients and is potentially coordinated by miRNA and tRNA metabolism alterations.<br><br>TRIAL REGISTRATION: COntAGIouS, NCT04327570. Registered 26 March 2020, https://clinicaltrials.gov/ct2/show/NCT04327570.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07665-y.},
}
@article {pmid41566332,
year = {2026},
author = {Penuelas, VL and Pham, K and Frost, S and Harahap-Carrillo, IS and Vargas, A and Bergersen, KV and He, Y and Nair, MG and Kaul, M and Heinrich, EC},
title = {Long-term impacts of COVID-19 on systemic inflammation and control of breathing reflexes: an observational cohort study.},
journal = {Respiratory research},
volume = {27},
number = {1},
pages = {70},
pmid = {41566332},
issn = {1465-993X},
mesh = {Humans ; *COVID-19/physiopathology/blood/diagnosis/epidemiology ; Male ; Female ; Middle Aged ; *Reflex/physiology ; Cohort Studies ; Aged ; Adult ; *Inflammation/physiopathology/blood ; Time Factors ; *Respiration ; },
abstract = {BACKGROUND: The COVID-19 pandemic resulted in over 7 million reported deaths and over 700.4 million reported infections to-date. Many individuals who recover from COVID-19 report prolonged dyspnea, sometimes persisting for months. Furthermore, COVID-19 has been linked to systemic and neuronal inflammation which may have downstream impacts on the neural control of breathing. Therefore, we hypothesized that individuals recovered from COVID-19 may exhibit changes in their ventilatory chemosensitivity to carbon dioxide and hypoxia, and that these changes may be linked to systemic inflammation.<br><br>METHODS: To test this hypothesis, we measured baseline ventilatory patterns and chemoreflex sensitivity in individuals recovered from COVID-19 (n&#x2009;=&#x2009;77) and individuals with no prior COVID-19 infection (n&#x2009;=&#x2009;41). Peripheral venous blood samples were also collected for inflammatory biomarker expression and profiling.<br><br>RESULTS: Recovered participants demonstrated a small but progressive decrease in the hypercapnic ventilatory response under a co-stimulus with hypoxia (control vs. 24-month post-recovery; p&#x2009;=&#x2009;0.023). Additionally, we identified several significant correlations between plasma inflammatory markers and ventilatory chemoreflex characteristics, including a positive correlation between SAA and CRP and the ventilatory response to hypoxia (p&#x2009;<&#x2009;0.05 within recovered and control cohorts). Finally, expression of six vascular inflammatory markers (Myoglobin, NGAL, MMP-2, OPN, IGFBP-4, and Cystatin C) was unexpectedly decreased in recovered participants compared to the control cohort for up to one-year post recovery.<br><br>CONCLUSIONS: Overall, this data indicates that COVID-19 and other acute viral infections may have a modest impact on the chemoreflex control of breathing as well as systemic inflammatory profiles, and that these changes may be linked to each other. These findings may strengthen our understanding of the pathology of long-COVID symptoms.},
}
@article {pmid41565056,
year = {2026},
author = {Uematsu, T and Nojiri, S and Nagao, M and Ishijima, M and Nishizaki, Y},
title = {Comprehensive analysis of risk factors for coronavirus disease 2019 infection and post-infection sequelae based on real-world data from a health insurance database in Japan.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {164},
number = {},
pages = {108405},
doi = {10.1016/j.ijid.2026.108405},
pmid = {41565056},
issn = {1878-3511},
abstract = {OBJECTIVES: Using real-world data from Japan, this study aimed to examine disease risks in COVID-19 patients before and after infection.<br><br>METHODS: We used the Japanese Health Insurance Database to identify hospitalized patients in Japan aged 60 years who were newly diagnosed with COVID-19 by December 31, 2020. To form the study population, these patients were matched 1:1 with individuals without COVID-19 on the basis of age, sex, and index date. Two analytical approaches were employed: a case-control study using conditional logistic least absolute shrinkage and selection operator (LASSO) regression to identify risk factors for COVID-19 infection and a retrospective cohort study using time-to-event analysis to evaluate the risk of developing sequelae following infection.<br><br>RESULTS: Overall, 8072 patients were included (4036 in each group). Organic, including symptomatic mental disorders demonstrated the strongest association (odds ratio, 2.276). Following infection, behavioral syndromes associated with physiological disturbances and physical factors exhibited the highest risk of developing new conditions (hazard ratio [HR], 3.523; 95% confidence interval [CI], 2.101-5.907), followed by pulmonary heart disease and diseases of the pulmonary circulation (HR, 2.954; 95% CI, 1.360-6.420).<br><br>CONCLUSION: Our findings suggest an association between COVID-19 and mental and behavioral disorders.},
}
@article {pmid41564976,
year = {2026},
author = {Karaviti, D and Charakida, M and Dimopoulou, D and Marmarinos, A and Papadaki, M and Maritsi, D and Spyridis, N and Avgeris, M and Gourgiotis, D and Syggelou, A and Tsolia, M},
title = {Long term cardiovascular effects on COVID-19 infection in children. The need for monitoring.},
journal = {International journal of cardiology},
volume = {449},
number = {},
pages = {134188},
doi = {10.1016/j.ijcard.2026.134188},
pmid = {41564976},
issn = {1874-1754},
mesh = {Humans ; Child ; *COVID-19/complications/physiopathology/epidemiology/blood ; Male ; Female ; Adolescent ; Prospective Studies ; Child, Preschool ; Case-Control Studies ; Echocardiography/methods ; *Cardiovascular Diseases/epidemiology/etiology/physiopathology/diagnostic imaging ; SARS-CoV-2 ; Time Factors ; },
abstract = {BACKGROUND: Although SARS-CoV-2 infection has been associated with mild illness in children, concerns have emerged regarding potential long-term cardiovascular and systemic effects, even in previously healthy pediatric populations.<br><br>OBJECTIVE: The aim of this study is to assess cardiac function and long-term symptoms in children up to one year after COVID-19 infection, and to compare these findings with healthy controls without prior SARS-CoV-2 exposure.<br><br>METHODS: In this prospective case-control study, children aged 4-17&#xa0;years were divided into two groups: those with a confirmed history of COVID-19 (Group 1) and healthy controls (Group 2). Participants underwent echocardiographic evaluation-including global longitudinal strain (GLS) analysis and biochemical testing, including lipid profile and intracellular adhesion molecule -1 (ICAM-1) measurements. A structured symptom survey was used to assess cardiovascular and systemic long-COVID manifestations.<br><br>RESULTS: Conventional echocardiographic indices did not differ significantly between groups. However, Group 1 showed a persistent reduction in left ventricular GLS, indicating subclinical myocardial dysfunction (p&#xa0;<&#xa0;0.05). Long-COVID symptoms were reported in 23.6% of children in Group 1, with fatigue being the most common (16.6%), followed by palpitations (2.0%). Lipid profiles were similar between groups, although children with moderate to severe infections exhibited significantly elevated serum intracellular adhesion molecule-1 (sICAM-1) levels, suggestive of endothelial activation.<br><br>CONCLUSION: Even in the absence of overt cardiovascular disease, children with prior SARS-CoV-2 infection experience persistent subclinical cardiac changes and symptoms consistent with Long-COVID. These findings highlight the need for ongoing surveillance and comprehensive cardiovascular assessments in pediatric populations following COVID-19 infection.},
}
@article {pmid41564615,
year = {2026},
author = {Chishtie, FA and Drozd, J and Li, X and Benterki, A and Valluri, SR},
title = {A robust compartmental modeling framework for infectious disease monitoring and analysis via fractional differential equations.},
journal = {Epidemics},
volume = {54},
number = {},
pages = {100887},
doi = {10.1016/j.epidem.2026.100887},
pmid = {41564615},
issn = {1878-0067},
abstract = {This study presents a comprehensive framework for infectious disease monitoring using fractional differential equations, specifically developing the SEIQRDP (Susceptible, Exposed, Infected, Quarantined, Recovered, Deceased, Protected) model. Traditional compartmental models are extended by incorporating fractional calculus, with orders α∈(0,2], which provides enhanced flexibility in capturing memory effects and non-local behaviors inherent in disease transmission dynamics. The framework demonstrates improved accuracy when fitted to Canadian COVID-19 data compared to classical integer-order models, with Wave 1 achieving 22.1% improvement (95% CI: 17.4-26.8%) and Wave 2 achieving 6.2% improvement (95% CI: 3.1-9.3%) in predictive accuracy (average ∼14%). Fractional orders both below and above unity yield superior fits to empirical data depending on epidemic phase, successfully capturing multi-wave dynamics across different pandemic phases. The model incorporates time-dependent parameters to account for varying intervention strategies. Rigorous mathematical analysis including existence, uniqueness, and stability of solutions is provided alongside comprehensive sensitivity analysis. Out-of-sample validation using rolling-origin cross-validation demonstrates robust forecasting performance across 7-, 14-, and 21-day horizons. This research provides public health authorities with an evidence-based tool for epidemic modeling, with proposed extensions for AI-enhanced surveillance, interoperability standards, and Long COVID monitoring discussed as future research directions.},
}
@article {pmid41563438,
year = {2026},
author = {Oliver-Mas, S and Matias-Guiu, JA and Delgado-Alonso, C and Valles-Salgado, M and Gil-Moreno, MJ and López-Carbonero, JI and Fernández-Romero, L and Cuevas, C and Delgado-Álvarez, A and Matias-Guiu, J and Diez-Cirarda, M},
title = {Episodic memory deficits and processes in post-COVID condition.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41563438},
issn = {1433-8491},
support = {INT20/00079//Instituto de Salud Carlos III/ ; FI20/000145//Instituto de Salud Carlos III/ ; CD22/00043//Instituto de Salud Carlos III/ ; CM23/00094//Instituto de Salud Carlos III/ ; G63-HEALTHSTARPLUS-HSP4//Fundaci&#xf3;n para el Conocimiento madri+d/ ; },
abstract = {Cognitive dysfunction is one of the most prevalent symptoms in patients with post-COVID condition (PCC) and episodic memory has been highlighted as one of the most impaired cognitive domains in these patients. However, few studies have specifically assessed episodic memory processes in these patients. This study aims to comprehensively investigate the memory function in patients with PCC. We conducted a cross-sectional study involving 157 patients with PCC and 74 healthy controls. Participants underwent a comprehensive neuropsychological assessment and memory assessment, including the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), the Free and Cued Selective Reminding test (FCSRT), the Open-Trial Selective Reminding Test (OT-SRT), and a Mental Ability Questionnaire (FLEI). We compared groups and evaluated the correlation between episodic memory and neuropsychological and clinical assessments. Patients with PCC showed reduced performance on the LASSI-L, the FCSRT and the OT-SRT compared to controls. The memory scores showed positive moderate correlations with attention tests and positive low correlations with language, visuospatial or executive functions. Subjective memory complaints were related to poorer memory performance. LASSI-L was the test most associated with subjective memory complaints, whereas OT-SRT was the test less influenced by attention tests. The study found multiple memory processes impaired in patients with PCC, specifically in initial encoding, learning information acquisition and storage, and in retrieval, with only partial improvement with cues and recognition, and with significant susceptibility to the effects of retroactive semantic interference. These findings are relevant for characterising the cognitive deficits of patients with PCC and for designing interventional strategies.},
}
@article {pmid41562619,
year = {2026},
author = {Tien, C-F and Lin, E-J and Tsai, W-H and Tsai, W-T and Chen, M-Y and Su, Y-S and Wu, H-C and Chiu, Y-T and Tung, W-J and Kuo, Y-P and Su, Y-W and Chen, H-W and Chen, F-J and Chuang, T-H and Wang, H-T and Yu, G-Y},
title = {SARS-CoV-2 spike protein expression drives post-acute coagulopathy.},
journal = {Journal of virology},
volume = {100},
number = {2},
pages = {e0125525},
pmid = {41562619},
issn = {1098-5514},
support = {IV-112-PP-10//National Health Research Institutes/ ; IV-113-PP-10//National Health Research Institutes/ ; IV-114-PP-10//National Health Research Institutes/ ; 113-2320-B-400-021//National Science and Technology Council/ ; },
mesh = {Animals ; *Spike Glycoprotein, Coronavirus/genetics/metabolism ; *COVID-19/virology/pathology/complications/blood ; Mice ; Humans ; *SARS-CoV-2/pathogenicity/metabolism/genetics ; Mice, Transgenic ; Disease Models, Animal ; Female ; Chemokine CXCL13/blood ; Male ; *Blood Coagulation Disorders/virology ; },
abstract = {During the COVID-19 pandemic, multiple SARS-CoV-2 variants emerged, each with distinct pathogenicity and transmissibility. This study investigated the role of the viral spike (S) protein in disease progression, focusing on the highly virulent S variant. The Delta S protein exhibited enhanced cleavage efficiency at the S1/S2 junction, resulting in partial dissociation of the S1 subunit, with detectable levels of extracellular S1. Unexpectedly, transient expression of Ancestral and Delta S protein induced by a recombinant vesicular stomatitis viral vector caused mild pulmonary inflammation, neutrophil activation, microthrombosis, and ~40% mortality in transgenic K18-hACE2 mice between 8 and 16 days, similar to post-COVID sequelae. The diseased mice displayed splenic atrophy and systemic inflammation, with elevated serum IGFBP-1 and CXCL13 levels. Consistent with the animal findings, serum samples from long COVID patients showed significantly elevated IGFBP-1 levels. CXCL13 levels were particularly elevated in patients with more severe long COVID symptoms. Notably, treatment with the antiplatelet agent aspirin significantly reduced both mortality and weight loss in mice exposed to Delta S protein expression. These findings suggest that SARS-CoV-2 S protein-associated coagulation and systemic inflammation during infection may contribute to the development of post-acute sequelae of COVID-19.IMPORTANCEOur study investigates the distinctive pathogenic properties of the SARS-CoV-2 spike (S) protein from highly virulent variants, with a particular focus on its delayed pathological effects in mice. Using a vesicular stomatitis virus (VSV) vector to transiently express the Ancestral and Delta variant S proteins in K18-hACE2 mice, we observed minimal acute symptoms initially; however, approximately 40% of the mice developed mild pulmonary inflammation, neutrophil activation, and microthrombosis, leading to death between 8 and 16 days post-infection. This delayed pathology was accompanied by elevated circulating levels of CXCL13 and IGFBP-1. Consistent with these findings, serum samples from long COVID patients also showed significantly increased IGFBP-1 levels, while CXCL13 levels were particularly elevated in individuals with more severe long COVID symptoms. These findings provide important observational evidence that may guide future mechanistic studies on long COVID and inform the development of potential therapeutic approaches.},
}
@article {pmid41562079,
year = {2025},
author = {Pridgen, WL and Putrino, D},
title = {Patient-reported improvements from use of IMC-2 alone and IMC-2 and Paxlovid[®] in a Long COVID cohort: a case series.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1698271},
pmid = {41562079},
issn = {1664-3224},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Antiviral Agents/therapeutic use/administration &amp; dosage ; Aged ; *SARS-CoV-2/drug effects ; *COVID-19/virology ; *COVID-19 Drug Treatment ; Adult ; Patient Reported Outcome Measures ; Drug Therapy, Combination ; Treatment Outcome ; },
abstract = {INTRODUCTION: Long COVID (LC) is an infection-associated chronic condition and illness (IACCI) with no currently approved treatments. In order to address SARS-CoV-2 persistence and herpesvirus reactivation, which have been implicated as drivers of LC, sustained use of antiviral combinations may be useful in treating patients with the illness.<br><br>METHODS: A convenience sample of patients undergoing an extended course of antiviral therapy was studied. Patients received either 120 days of IMC-2 only (IO) or 120 days of IMC-2 with the addition of 15 days of Paxlovid (IP), prescribed off-label at an outpatient clinic for people with LC. The Patient Global Impression of Change (PGIC) was used to measure therapy response over time, with primary focus on fatigue and secondary focus on brain fog and dysautonomia. Visual analog scales (VAS) were also used to track perceived symptom improvements.<br><br>RESULTS: A total of 27 people with LC were approached for treatment, of whom 24 completed one or both protocols. Twelve received the IO protocol, and 12 received the continuous IP combination. Both groups reported reductions in fatigue on the PGIC, but participants receiving IP experienced a statistically significant improvement compared with those receiving IO (p < 0.0001). Similarly, using a VAS, patients in the IP group reported an average 55.3% (p < 0.0001) greater reduction in fatigue than the IO group. Participants who completed the IP intervention demonstrated durable clinical benefit, with symptom improvements remaining consistent at 120-, 305-, and 731-day follow-ups.<br><br>DISCUSSION: This small, open-label case series provides pilot evidence supporting the need for a larger trial of combination antivirals for people living with LC. Based on these results, a larger, controlled trial of IMC-2 paired with Paxlovid is recommended.},
}
@article {pmid41561147,
year = {2026},
author = {Kröpfl, JM and Hauser, C and Beugger, L and Hanssen, H and Schwendinger, F and Schmidt-Trucksäss, A},
title = {Circulating angiogenic progenitor cell apoptosis in Post-COVID-19 syndrome.},
journal = {International journal of cardiology. Heart &amp; vasculature},
volume = {62},
number = {},
pages = {101866},
pmid = {41561147},
issn = {2352-9067},
abstract = {BACKGROUND: Cellular endothelial dysfunction in patients recovering from Coronavirus disease 2019 (COVID-19) remains poorly understood. This study examined circulating angiogenic progenitor cells (CAC) and mature endothelial cells (CEC) in individuals with persistent symptoms following hospitalization for COVID-19 (PH-PCS) at ≥ 18-months post-infection.<br><br>METHODS: We compared PH-PCS (n&#xa0;=&#xa0;14) to matched controls without symptomatic COVID-19 (n&#xa0;=&#xa0;7). Examinations included macro- and microvascular structure and function and the analysis of CAC and CEC using flow cytometry.<br><br>RESULTS: Estimates indicated somewhat lower apoptotic CAC concentrations (mean difference[md] [95&#xa0;%CI]&#xa0;=&#xa0;0.050 cells/&#xb5;l [0.003, 0.137], p&#xa0;=&#xa0;0.084) and proportions (% total CAC, 7.7 percentage points (pp) [0.3, 12.9], p&#xa0;=&#xa0;0.066) in patients compared to controls, though estimates were imprecise. Similar results were observed for apoptotic CEC concentrations (1.202 cells/&#xb5;l [0.040, 7.518], p&#xa0;=&#xa0;0.066) and proportions (% total CEC, 2.7&#xa0;pp [0.2, 23.8], p&#xa0;=&#xa0;0.048). Live CAC (-7.6&#xa0;pp [-12.7, -1.1], p&#xa0;=&#xa0;0.084) and live CEC proportions (-4.9&#xa0;pp [-23.7, -0.3], p&#xa0;=&#xa0;0.042) were somewhat enhanced in PH-PCS. Brachial-arterial flow-mediated dilation (baFMD) and retinal vessel imaging parameters showed little evidence for differences between groups, except for maximal arteriolar constriction, where estimates suggested on average higher values in PH-PCS (md [95&#xa0;%CI]&#xa0;=&#xa0;1.64 [0.050, 3.63], p&#xa0;=&#xa0;0.084), but estimates were uncertain. Pooling PH-PCS and controls, correlations were observed between reduced baFMD and both elevated total CEC concentrations (&#x3c1;&#xa0;=&#xa0;-0.56, p&#xa0;=&#xa0;0.038) and decreased apoptotic CAC proportions (&#x3c1;&#xa0;=&#xa0;0.56, p&#xa0;=&#xa0;0.042).<br><br>CONCLUSIONS: This study suggests the possibility of unbalanced CAC and CEC apoptosis in PH-PCS, but with uncertain magnitude. The findings might inform hypothesis generation for future studies on (cellular) endothelial function in PH-PCS.},
}
@article {pmid41559790,
year = {2026},
author = {García-Hidalgo, MC and Mota-Martorell, N and González, J and Benítez, ID and Company-Marín, I and Jové, M and Barbé, F and Amigó, N and Pamplona, R and de Gonzalo-Calvo, D and Torres, G},
title = {Multilayer metabolomic integration reveals bioenergetic disruption in Long COVID.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {237},
pmid = {41559790},
issn = {1479-5876},
abstract = {BACKGROUND: Long COVID represents a significant health challenge, with 10–20% of patients with COVID-19 experiencing persistent multiorgan symptoms. The heterogeneity of clinical manifestations, combined with an incomplete understanding of the underlying molecular mechanisms, limits the improvement of patient management. Circulating metabolomic profiling constitutes a promising tool to address these limitations. In this context, we aim to investigate long-term metabolic disruptions in Long COVID through multilayer integration of plasma metabolites.<br><br>METHODS: The study population included 42 survivors of critical COVID-19 who attended a comprehensive clinical evaluation conducted 12&#x2009;months postdischarge. Plasma biochemicals, including lipoproteins, lipids, glycoproteins and metabolites were quantified using proton nuclear magnetic resonance spectroscopy (H-NMR). Circulating tricarboxylic acid (TCA) cycle intermediates and protein damage markers were detected by gas chromatography&#x2012;mass spectrometry (GC/MS). A machine learning-based feature selection approach was employed to identify the multilayered metabolic signature. Generalized additive models (GAMs) were used to explore associations between individual metabolites and specific dimensions of Long COVID.<br><br>RESULTS: Univariate analysis revealed significantly elevated levels of alpha-ketoglutarate (aKG) and reduced levels of creatine in patients with Long COVID. A nine-metabolite and damage marker signature [aKG, carboxymethyl-cysteine (CMC), carboxymethyl-lysine (CML), creatine, fumarate, lactate, low density lipoprotein particle size (LDL-Z), 2-succinyl-cysteine (2SC) and tyrosine] was identified through the integration of Random Forest with Boruta and Sparse Partial Least Squares regression. This signature effectively classified patients with Long COVID (a cross-validated AUC of 0.91). In the GAM models, aKG, CMC, CML and creatine were associated with distinct Long COVID dimensions, including cognitive, functional and respiratory impairments.<br><br>CONCLUSIONS: Multilayer metabolomic integration reveals persistent bioenergetic disruption in patients with Long COVID. The identified metabolic profile offers promising biomarkers for medical decision-making. Modulating key metabolites could potentially mitigate specific symptoms of long COVID.<br><br>GRAPHICAL ABSTRACT: [Image: see text]<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07684-3.},
}
@article {pmid41559785,
year = {2026},
author = {Inderyas, M and Thapaliya, K and Marshall-Gradisnik, S and Barnden, L},
title = {Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {236},
pmid = {41559785},
issn = {1479-5876},
abstract = {BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and long COVID are chronic debilitating illnesses featuring fatigue, post-exertional malaise (PEM) and neurocognitive deficits. Temporal correlation of neural activity between distinct brain regions, also referred to as functional connectivity (FC), can provide insights into how brain networks coordinate, at rest or during task. Therefore, we explored intrinsic FC correlates of cognitive fatigue in ME/CFS and long COVID patients during two Stroop-colour-word paradigms on 7 Tesla fMRI.<br><br>METHODS: 450 sagittal volumes were acquired from seventy-eight participants: 32 patients with MECFS (pwME/CFS); 19 long COVID (pwLC) and 27 healthy controls (HC) during performance of baseline or Pre (before/during fatigue build-up) and repeat Post (fatigue set-in) Stroop tasks. Structural and functional data were analysed using the CONN toolbox.<br><br>RESULTS: Regions of interest (ROI-to-ROI) analysis revealed significantly increased FC in subcortical regions in HC for Pre vs Post. Relative to HC, pwLC showed significantly reduced FC between nucleus accumbens and vermis 3 (p&#x2009;=&#x2009;0.02) in Pre and increased FC in the prefrontal cortex and hippocampus (p&#x2009;=&#x2009;0.02) in Post. pwME/CFS showed a significantly increased FC between the left cuneiform nucleus and right medulla (p&#x2009;=&#x2009;0.03). Compared to HC, reduced FC was significant in pwLC during Pre, and between medulla and hippocampus (p&#x2009;=&#x2009;0.04) and between nucleus accumbens and vermis (p&#x2009;=&#x2009;0.001) during Post. Aberrant FC was significant for pwME/CFS in core networks during Pre. Core network FC to the cerebellum, amygdala, caudate and red nucleus correlated with symptom scores for cognition in both pwME/CFS and pwLC. Hippocampus and cerebellar FC correlated with duration of illness in pwME/CFS.<br><br>CONCLUSIONS: Our findings of reduced dopaminergic hippocampal-nucleus-accumbens connectivity imply blunted motivation and cognition. Extensive FC differences in subcortical and core networks in patient cohorts were detected relative to an increased FC in HC. High regional communication indicative of greater task engagement by HC was distinctive while FC differences in ME/CFS and long COVID patients indicated reduced and dysregulated regional coordination that may serve as candidate biomarkers of symptomatology in long COVID and ME/CFS.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07708-y.},
}
@article {pmid41559736,
year = {2026},
author = {Kontou, K and Daynes, E and Singh, SJ and Evans, RA and Gardiner, N and Chaplin, E and Richardson, M and Bishop, N and Creese, J and Bateman, N and Wright, A and Zivtins, E and Houchen-Wolloff, L},
title = {The effectiveness and acceptability of face-to-face rehabilitation for patients with Long Covid who were not hospitalised with their acute infection: a mixed-methods study comprising a randomised controlled trial (RCT) with embedded qualitative component.},
journal = {Trials},
volume = {27},
number = {1},
pages = {132},
pmid = {41559736},
issn = {1745-6215},
support = {/WT_/Wellcome Trust/United Kingdom ; 223512/Z/21/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *COVID-19/rehabilitation/complications ; Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; Patient Acceptance of Health Care ; Hospitalization ; SARS-CoV-2 ; Exercise Tolerance ; },
abstract = {BACKGROUND: Long Covid is a term used to describe a multisystem condition that presents with a myriad of physical and psychological symptoms that continue or develop after acute COVID-19. Long Covid is a significant public health problem because of the nature of the illness, its negative impfact on everyday functioning, and the healthcare inequalities evident in access and experience, notably in terms of ethnicity and socioeconomic status. Evidence in patients hospitalised with their acute infection suggests exercise-based rehabilitation could be helpful to improve exercise tolerance, respiratory symptoms, fatigue, and cognition; however, research is needed to determine whether exercise-based rehabilitation is effective and acceptable for patients with Long Covid who were not hospitalised.<br><br>METHODS: This mixed-methods study comprises a single-centre, randomised controlled trial to determine whether face-to-face rehabilitation increases exercise capacity compared to usual care alone in non-hospitalised patients with Long Covid, with embedded qualitative components to explore intervention acceptability in the context of healthcare inequalities. Usual care is as defined by the National Institute for Clinical Excellence (NICE) Covid-19 guidance. The rehabilitation intervention will take place twice a week for 6 weeks and will combine symptom-titrated exercise with self-management education. The proposed sample size of 56 for the randomised controlled trial is calculated on the primary outcome of Incremental Shuttle Walking Test (ISWT) distance, with a change of 50metres (m) at 90% power, a standard deviation of 17&#xa0;m, and a 0.05 type 1 error.<br><br>DISCUSSION: A mixed-methods approach has been chosen as quantitative data alone would be insufficient to answer the research question, and mixing the data will enable a more comprehensive understanding and ensure there is an equal focus on outcomes and experiences of a face-to-face exercise-based rehabilitation programme. A healthcare inequalities lens will explore who may be under-represented, with the qualitative work providing further evidence as to why this may be the case. It is recognised that meeting recruitment targets in the context of reducing referral rates and funding for Long Covid services may prove challenging.<br><br>TRIAL REGISTRATION: ISRCTN trial registry (ISRCTN33340595). Registered on 30 September 2024.},
}
@article {pmid41559316,
year = {2026},
author = {Shi, Y and Li, B and Zheng, Y and Xue, C and Zhu, J},
title = {Therapeutic effect of anti-neuroinflammatory supplement combined with olfactory training on post-covid olfactory dysfunction: a systematic review and meta-analysis.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {},
number = {},
pages = {},
pmid = {41559316},
issn = {1434-4726},
abstract = {BACKGROUND: There is no established specific treatment for post-COVID olfactory dysfunction (PCOD) currently. Olfactory training (OT) is the only effective intervention supported by clinical evidence. The anti-neuroinflammatory supplement palmitoylethanolamide and luteolin (PEA-LUT) has shown potential in alleviating the symptoms of post-COVID, but its therapeutic effect on olfactory dysfunction and the gain effect when combined with OT remain to be evaluated.<br><br>METHODS: We comprehensively searched the online databases EMBASE, PubMed, ScienceDirect, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrials.govfor the literature related to the treatment of PCOD, identified studies reporting the efficacy of PEA-LUT combined with OT, extracted the treatment outcome data, and performed data synthesis.<br><br>RESULTS: A total of 7 eligible RCTs published between 2021 and 2024 were included, comprising 525 patients with PCOD. Of the seven studies, five (71.4%) used the full Threshold-Discrimination-Identification (TDI) scoresystem to assess olfactory function, while two (28.6%) used only the Identification ("I") subscale; 332 patients (63.2%) received PEA-LUT&#x2009;+&#x2009;OT therapy and 203 (38.8%) received OT alone. Meta-analysis of these studies showed that patients receiving PEA-LUT combined with OT had significantly higher TDI scores compared to those receiving OT alone (Standard mean difference (SMD)&#x2009;=&#x2009;0.90; 95% CI: 0.24-1.58; P&#x2009;<&#x2009;0.01). The overall response rate was also significantly higher in the combination group (Risk difference (RD)&#x2009;=&#x2009;0.33; 95% CI: 0.01-0.64; P&#x2009;=&#x2009;0.04).<br><br>CONCLUSION: The neuroprotective properties of PEA-LUT appear to enhance recovery from post-COVID olfactory dysfunction. When combined with olfactory training, this treatment shows promising potential as a novel therapeutic approach.},
}
@article {pmid41558579,
year = {2026},
author = {Chen, G and Zhou, S and Chen, Y and Zhou, J and Wang, N and Feng, Y},
title = {OLink proteomic biomarker to predict clinical efficacy of Macaranga sinensis Müll.Arg: A nested case-control study.},
journal = {Journal of ethnopharmacology},
volume = {361},
number = {},
pages = {121243},
doi = {10.1016/j.jep.2026.121243},
pmid = {41558579},
issn = {1872-7573},
mesh = {Humans ; Biomarkers/blood ; Male ; Female ; Case-Control Studies ; Middle Aged ; Proteomics/methods ; Adult ; *Fatigue/drug therapy/blood/etiology ; *COVID-19/complications/blood ; *COVID-19 Drug Treatment ; *Drugs, Chinese Herbal/therapeutic use ; Aged ; Treatment Outcome ; },
abstract = {Despite the fact that herbal medicine has been used for a long time, their clinical application is challenged by unclear active ingredients and poorly understood mechanisms of action, resulting in considerable heterogeneity in therapeutic outcomes among patients.<br><br>AIM OF THE STUDY: To explore the use of OLink-based biomarkers to predict the efficacy of Macaranga sinensis M&#xfc;ll.Arg in individuals with long COVID-related fatigue.<br><br>MATERIALS AND METHODS: This nested case-control study recruited long COVID participants who had routinely taken Macaranga sinensis M&#xfc;ll.Arg for more than three months. Case (response) and control (non-response) group were defined based on the change in Brief Fatigue Inventory (BFI) score. Plasma samples were analyzed using OLink. Mann-Whitney U test, Lasso and Ridge regression model, Random Forest, and Support Vector Machine (SVM) were used for differential expression analysis, feature selection, and biomarker identification, respectively.<br><br>RESULTS: A total of 55 long COVID fatigue patients was included in this study (27 in case group and 28 in control group). Differential expression analysis filtered in a total of 13 potential biomarkers (log2 fold change >0.5; p&#xa0;<&#xa0;0.05). Feature selection further selected 11 biomarkers, including uPA, TRAIL, IL-10, IL-18R1, CX3CL1, EPHB4, COL1A1, Flt3L, EGFR, IL-1RT2, and IFN-&#x3b3; (all p&#xa0;<&#xa0;1e-6). Random Forest and SVM identified the key biomarker of CX3CL1 (F1-score of 0.72).<br><br>CONCLUSIONS: Our exploratory analysis suggests that CX3CL1 is the candidate biomarker for predicting the efficacy of Macaranga sinensis M&#xfc;ll.Arg, warranting further investigation in larger studies. Our work highlights the translational potential of integrating statistical modeling and machine learning approaches with proteomic data to identify predictive biomarkers for herbal medicine efficacy in clinical settings.},
}
@article {pmid41557618,
year = {2026},
author = {Rohner, S and Schnepper, R and Meienberg, A and Bopp, K and Mayr, M and Meinlschmidt, G and Schaefert, R},
title = {Protocol of the digital long COVID study: A single-center, registry-based, feasibility and clinical evaluation study to investigate a 12-week digital intervention program for people affected by post-COVID-19 condition.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0340385},
pmid = {41557618},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/complications/therapy ; Feasibility Studies ; Registries ; SARS-CoV-2/isolation &amp; purification ; Telemedicine ; Male ; Female ; },
abstract = {Up to 400 million individuals globally are estimated to experience persistent symptoms, including fatigue, muscle pain, and brain fog, following severe acute respiratory syndrome coronavirus type 2 infection. These persistent symptoms are referred to as Post-COVID-19 condition if they last for more than 12 weeks after infection and persist for at least 8 weeks and often causing significant distress and burden. The underlying pathological mechanisms have not yet been fully elucidated. Due to the heterogeneity of the disease a multifactorial origin is highly likely. Overall, evidence on optimal management is limited, and no medication has yet proven to be effective. Current symptom management and treatment guidelines suggest a biopsychosocial perspective and emphasize multidisciplinary approaches. Comprehensive interventions, adequate treatment access, and appropriate resources remain insufficiently available and implementing digital interventions might help mitigate these limitations. This protocol details a single-site feasibility and clinical evaluation study aiming to bridge this gap. By implementing an exploratory, open-label, digital interventional approach this study investigates the feasibility and efficacy of a 12-week program delivered by a cloud-based application. The program consists of 13 modules encompassing a wide range of topics (e.g., energy management, self-care, stress management) and includes informational (e.g., psychoeducational content) and interactive (e.g., exercises, self-reflection diaries) components. Customization options align the material with participant needs. A dedicated feedback section in each module captures feedback regarding usability and feasibility. Participants are monitored and checked for adherence throughout the study. The primary outcome is the post-intervention change in functional capacity measured by the World Health Organization Disability Assessment Schedule 2.0. All participants provide written informed consent. Key results from the study will be published in peer-reviewed journals.},
}
@article {pmid41552054,
year = {2025},
author = {Virno, T and Tomilonus, N and Hart, J and Van Rensburg, C and Walsh, D},
title = {COVID-19-Associated Cystitis: De Novo Urinary Urgency Following SARS-CoV-2.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99386},
pmid = {41552054},
issn = {2168-8184},
abstract = {COVID-19 is widely recognized as a systemic disease with pulmonary, cardiovascular, and neurologic manifestations, yet growing evidence highlights the genitourinary tract as another important site of involvement. A distinct clinical entity, COVID-associated-cystitis (CAC), has been described in which patients develop de novo or worsening lower urinary tract symptoms (LUTS), such as urgency, frequency, and nocturia, without bacterial infection. This case report describes a 71-year-old woman who developed persistent urinary urgency following recovery from COVID-19, successfully treated with oxybutynin. The case is contextualized within the expanding literature on CAC, including evidence from biomarker studies, mechanistic analyses, and large cohort investigations. Emerging data support a pathophysiologic role for both inflammatory cytokine release and viral receptor expression in the bladder, with symptom overlap between CAC, overactive bladder (OAB), and interstitial cystitis. Recognition of CAC is clinically significant, preventing misdiagnosis as bacterial cystitis and guiding management using established OAB frameworks. The case underscores the importance of considering genitourinary sequelae of COVID-19 and contributes to the growing discussion on long COVID and bladder health.},
}
@article {pmid41551009,
year = {2025},
author = {Wang, B and Wang, Y and Ning, K},
title = {Unveiling the role of the respiratory microbiome in long COVID pathogenesis and therapeutics.},
journal = {Chinese medical journal pulmonary and critical care medicine},
volume = {3},
number = {4},
pages = {221-224},
pmid = {41551009},
issn = {2772-5588},
}
@article {pmid41550084,
year = {2026},
author = {Slack, IF and O'Shea, KM and Freigeh, GE and Franco, LM and Jaafar, S and Schuler, CF and Baker, JR},
title = {COVID-19 mRNA revaccination is safe and well tolerated in individuals with previous adverse reactions to the vaccine and/or long COVID.},
journal = {The journal of allergy and clinical immunology. Global},
volume = {5},
number = {2},
pages = {100620},
pmid = {41550084},
issn = {2772-8293},
abstract = {BACKGROUND: Vaccine safety is a primary concern among those with a history of adverse reactions to coronavirus disease 2019 (COVID-19) mRNA vaccines. Retrospective data and cohorts of individuals with severe previous reactions suggest that revaccination is safe and well tolerated. However, prospective data are limited.<br><br>OBJECTIVE: We sought to prospectively assess safety and tolerability of COVID-19 mRNA vaccines in individuals with a history of adverse vaccine reactions and in individuals with long COVID.<br><br>METHODS: Adults with a self-reported adverse reaction to COVID-19 mRNA vaccination and/or long COVID underwent COVID-19 mRNA revaccination at the University of Michigan with 30-minute observations. Participants were contacted by telephone after 7 days to review interval adverse events.<br><br>RESULTS: A total of 103 participants received COVID-19 mRNA revaccination-91 with history of adverse vaccine reaction, 20 with long COVID, and 8 with both. Mean age at enrollment was 41.8 years, and women were 67% of the cohort. Five individuals (4.9%) developed immediate symptoms with revaccination. All 5 events were mild (Consortium for Food Allergy Research severity level 1). Vital signs were assessed prevaccination and 30 minutes postvaccination. At 7-day follow-up, 77% of participants reported at least 1 adverse event, with fatigue (33.7%), headache (29.7%), and muscle pain (28.7%) most commonly reported. No follow-up reactions were severe. Five of the 103 participants had incidentally elevated baseline serum tryptase. None of these participants experienced immediate symptoms with revaccination.<br><br>CONCLUSIONS: Revaccination with COVID-19 mRNA vaccines was safe and well tolerated among individuals with previous adverse COVID-19 mRNA vaccine reaction and/or long COVID.},
}
@article {pmid41548411,
year = {2026},
author = {Richard, L and Nisenbaum, R and Dyer, A and Mergarten, D and Brown, M and Stewart, S and Hwang, SW},
title = {Identifying potential post-COVID-19 condition among people experiencing homelessness using longitudinal symptom patterns: A prospective cohort study.},
journal = {Public health},
volume = {252},
number = {},
pages = {106148},
doi = {10.1016/j.puhe.2026.106148},
pmid = {41548411},
issn = {1476-5616},
mesh = {Humans ; *Ill-Housed Persons/statistics &amp; numerical data ; *COVID-19/epidemiology/complications ; Male ; Prospective Studies ; Female ; Middle Aged ; Adult ; Longitudinal Studies ; Ontario/epidemiology ; Canada/epidemiology ; SARS-CoV-2 ; },
abstract = {OBJECTIVES: People experiencing homelessness have high SARS-CoV-2 infection and re-infection burden, potentially leading to higher prevalence of post-COVID-19 condition (PCC). However, high baseline symptom rates may make identification of PCC difficult or impossible in this population. This study evaluates symptom patterns over time to assess their ability to identify potential PCC among individuals experiencing homelessness.<br><br>STUDY DESIGN: Prospective cohort study METHODS: We prospectively followed a large (n&#xa0;=&#xa0;736), representative cohort of people experiencing homelessness recruited at random from 62 sites in Toronto, Canada between June and September 2021. Participants were interviewed up to five times over approximately 12 months. Longitudinal patterns of twelve self-reported symptoms were assessed through latent transition analysis, and generalized estimating equations with logit link were applied to determine their association with known risk of potential PCC.<br><br>RESULTS: Among 736 participants, three latent statuses were identified: (1) 'No/Few Symptoms' (&#x2265;70&#xa0;%), (2) 'Non-Specific Symptoms' (15-23&#xa0;%), and (3) 'Infection-Related Symptoms' (&#x2264;5&#xa0;%). Statuses 2 and 3 were associated with being at risk of PCC following symptomatic infection (aOR 3.41 [95&#xa0;% CI 2.3-5.0] and 3.18 [95&#xa0;% CI 1.6-6.4]) but not with being at risk of PCC overall. Transition probabilities suggested PCC would mostly occur among individuals with symptoms at baseline. However, the clustered area under the curve was modest (0.70 [95&#xa0;% CI 0.65-0.75]), indicating symptom-based approaches are suboptimal for identification of potential PCC.<br><br>CONCLUSIONS: Self-reported symptoms do not reliably identify potential PCC among people experiencing homelessness, due to high rates of underlying symptoms and asymptomatic infections. Alternative, strengths-based approaches are recommended to more equitably identify post-COVID condition in this population.},
}
@article {pmid41547213,
year = {2026},
author = {Carrascosa Gil, A and Gabella Martín, M and Salazar Lozano, MDC and Tamayo Gómez, E and Rico Feijoo, J and Álvarez de Santullano, CA},
title = {[Long-term symptomatic follow-up of patients with Long COVID syndrome].},
journal = {Atencion primaria},
volume = {58},
number = {3},
pages = {103425},
pmid = {41547213},
issn = {1578-1275},
abstract = {OBJECTIVE: The primary aim of the study was to investigate the long-term symptom progression of long COVID. The secondary objective was to assess whether any treatment had an impact on symptom evolution.<br><br>DESIGN: Longitudinal, prospective, observational, uncontrolled study.<br><br>SETTING: Internal Medicine Department, R&#xed;o Hortega University Hospital (Valladolid).<br><br>PARTICIPANTS: 40 patients with long COVID (cases) and 40 volunteers (controls) of the same age and sex as the cases, who had experienced acute COVID-19 without developing long COVID.<br><br>MAIN MEASUREMENTS: Scales, indices, and questionnaires were sent by post to evaluate the main symptoms of long COVID. The following were assessed: fatigue (MFIS), emotional disorders (HADS), sleep disturbances (PSQI), cognitive impairments (MFE-30), dyspnea (mMRC), physical exercise (GPAQ), quality of life (SF-36), and pain (CPGS). The cases were reassessed after three years.<br><br>RESULTS: After three years, cases showed an improvement in dyspnea (mMRC), which decreased from 1.38 to 1.10 (p=0.014). Ten cases reported having followed aerobic and/or anaerobic physical exercise as treatment, and it was observed that their pain severity (CPGS) improved from 2.7 to 1.3 (p=0.039). In the remaining measurements, variations among cases did not reach statistical significance.<br><br>CONCLUSIONS: After three years of follow-up, patients with long COVID continued to have similar symptom scores to their initial assessments, and worse than those of the control group. Aerobic and/or anaerobic physical exercise may contribute to partially improving symptom evolution. .},
}
@article {pmid41543809,
year = {2026},
author = {Bozkir, C and Kartal, T and Hokelek, B},
title = {Obesity and Nutritional Vulnerability in long COVID: A Neuroinflammatory and Cognitive Perspective.},
journal = {Current nutrition reports},
volume = {15},
number = {1},
pages = {5},
pmid = {41543809},
issn = {2161-3311},
mesh = {Humans ; *Obesity/complications/physiopathology ; *COVID-19/complications ; *Nutritional Status ; *Neuroinflammatory Diseases ; SARS-CoV-2 ; Malnutrition/complications ; Cognition ; Inflammation ; Cognitive Dysfunction/etiology ; },
abstract = {PURPOSE OF REVIEW: To examine the interplay between obesity, nutritional vulnerability, and long COVID, with a particular focus on neuroinflammatory and cognitive outcomes. This review synthesizes emerging evidence on shared pathophysiological pathways and evaluates the therapeutic potential of dietary and weight management strategies.<br><br>RECENT FINDINGS: Cognitive symptoms such as brain fog and memory deficits are among the most persistent and disabling features of long COVID. Obesity is associated with more severe manifestations through pathways involving chronic systemic inflammation, compromised blood-brain barrier integrity, and neuroimmune dysregulation. Concurrently, malnutrition and poor diet quality including low intake of antioxidants, omega-3 fatty acids, and micronutrients may impair neuroplasticity and delay recovery. Interventions such as Mediterranean and ketogenic dietary patterns, as well as structured weight loss programs, show promise in reducing inflammation and improving cognitive outcomes. Obesity and suboptimal nutritional status amplify the neurocognitive burden of long COVID through shared pathophysiological mechanisms. Integrated care models that incorporate metabolic screening, nutritional assessment, and individualized dietary interventions may improve recovery trajectories. Public health strategies that address food quality, obesity prevention, and equitable access to nutrition care are essential for long-term resilience in the post-COVID era.},
}
@article {pmid41542038,
year = {2026},
author = {Kwissa, M and Mathayan, M and Salunkhe, SS and Bakthavachalam, V and Ye, Z and Sanborn, MA and Condo, S and Upadhye, A and Nemakal, A and Wang, H and Chan, J and Richner, JM and Basu, S and Novak, RM and Jacobson, JR and Ganesh, BB and Cerda, M and Brim, H and Erdmann, NB and Levy, BD and Marshall, GD and McComsey, GA and Metz, TD and Okumura, MJ and Peluso, MJ and Walker, T and Utz, PJ and Krishnan, JA and Prabhakar, BS and Rehman, J},
title = {Persistent Immune Dysregulation during Long COVID is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41542038},
issn = {2693-5015},
support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; },
abstract = {Long COVID (LC) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of LC, but the extent of LC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed LC. Compared to convalescent, LC participants with a broad range of LC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the LC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa-associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in LC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in LC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity.},
}
@article {pmid41541965,
year = {2025},
author = {Zhang, L and Li, L and Chen, J and Pang, S and Zhang, Z and Yan, Y},
title = {Psychological Burden of Long COVID and Associated Factors Among Nurses Two Years Post-infection: A Cross-Sectional Study.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99231},
pmid = {41541965},
issn = {2168-8184},
abstract = {BACKGROUND: The COVID-19 pandemic has generated sustained physical and psychological impacts on healthcare workers. Growing evidence suggests that some individuals develop persistent multisystem manifestations long after the acute phase, collectively referred to as long COVID. Nurses, who have borne heavy workloads and ongoing psychological stress since the pandemic, may be particularly vulnerable; however, limited research has examined their mental health status two years after infection.<br><br>AIMS: This study aimed to evaluate anxiety and depression levels among nurses two years after COVID-19 infection, compare psychological characteristics across clinical departments, and identify factors associated with long COVID.<br><br>METHODS: A cross-sectional online survey was conducted among nurses at a tertiary hospital, yielding 735 valid responses. Data were collected using a general information questionnaire, the Generalized Anxiety Disorder-7 (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9). Participants were categorized into long COVID (n = 263) and non-long COVID (n = 472) groups. Between-group differences were examined using appropriate parametric or non-parametric tests, and variables with P < 0.10 were entered into multivariable logistic regression to identify independent predictors.<br><br>RESULTS: Nurses with long COVID were significantly older and exhibited higher GAD-7 and PHQ-9 scores than those without long COVID (all P < 0.001). Multivariate analysis showed that higher PHQ-9 scores (odds ratio (OR) = 1.147, 95% confidence interval (CI): 1.108-1.188) and older age (OR = 1.040, 95% CI: 1.011-1.070) were independently associated risk factors for long COVID. Although the prevalence of long COVID did not differ significantly across departments (P = 0.378), anxiety and depression levels varied, with nurses in high-risk exposure departments reporting higher GAD-7 and PHQ-9 scores than those in outpatient and medical-technical departments.<br><br>CONCLUSION: Two years after infection, nurses with long COVID continue to experience substantial psychological burden, particularly among older individuals and those with more severe depressive symptoms. Although long COVID was evenly distributed across clinical departments, significant interdepartmental differences in anxiety and depression underscore the influence of work characteristics and environment. Targeted psychological support and ongoing mental health monitoring are warranted to promote recovery and enhance occupational resilience in the post-pandemic era.},
}
@article {pmid41538643,
year = {2026},
author = {Segur, PC and Natarelli, TRP and Fonseca, LMM},
title = {Simulated scenario of nursing consultation for long COVID in primary health care.},
journal = {Revista gaucha de enfermagem},
volume = {46},
number = {},
pages = {e20240376},
doi = {10.1590/1983-1447.2025.20240376.en},
pmid = {41538643},
issn = {1983-1447},
mesh = {Humans ; *COVID-19/nursing ; *Primary Health Care ; *Education, Nursing/methods ; *Patient Simulation ; *Simulation Training ; *Referral and Consultation ; Female ; *Education, Nursing, Baccalaureate/methods ; },
abstract = {OBJECTIVE: To develop a simulated scenario for undergraduate education on nursing consultation in long COVID situations in Primary Health Care.<br><br>METHOD: This is an applied methodological study divided into two stages: first, the clinical case was constructed and validated with nurses with experience in Primary Health Care and/or clinical simulation (n=9). Then, the scenario was constructed and validated with a group of judges composed of professors and postgraduate students (n=11). The Content Validity Index was used to analyze the data, with an agreement level of 80%.<br><br>RESULTS: The clinical case and the scenario obtained an average Content Validity Index of 0.98 and 0.90, respectively. Only two items presented values below the minimum acceptable, being reformulated and sent for a second round of validation.<br><br>CONCLUSION: The simulated scenario on long COVID was developed and validated, demonstrating its potential for use in undergraduate nursing education and for contributing to professional training in Primary Health Care.},
}
@article {pmid41537076,
year = {2025},
author = {Singhal, A and Sahoo, D and Patle, A and Patil, S and Lakkireddy, M and Raja, S and Pyati, A and Arora, A and Dhole, S and Sakthivadivel, and Patil, P and Taranikanti, M and John, NA and Ravi, N},
title = {Evaluation of Inflammatory Biomarkers in Post-COVID-19 Arthritis: a Cross-Sectional Study from Telangana, South India.},
journal = {Maedica},
volume = {20},
number = {4},
pages = {701-707},
pmid = {41537076},
issn = {1841-9038},
abstract = {BACKGROUND: Long COVID, a post-COVID-19 syndrome, has been linked to various musculoskeletal manifestations, particularly arthritic symptoms. This study aimed to evaluate the inflammatory markers associated with long COVID in patients diagnosed with COVID arthritis.<br><br>METHODS: A cross-sectional prospective study was conducted in a tertiary care centre in Telangana, India, involving 139 PCR-confirmed COVID-19 patients diagnosed with arthritis. Eligible participants were COVID-free for one month to six months. Clinical histories, including severity of arthritis symptoms, levels of inflammatory markers (LDH, uric acid, serum ferritin, rheumatoid factor [RF] and CRP) and radiological investigations (radiographs and ultrasound) were recorded and analyzed. Follow-up assessments occurred at six months, with repeated measurements of inflammatory markers for statistical significance.<br><br>RESULTS: The predominant clinical presentations included joint aches, restricted movement, swelling, myalgia and fatigue, with 95% of subjects relying on over-the-counter analgesics. Notably, all measured inflammatory markers decreased over the six-month follow-up, with statistically significant reductions being observed in LDH, RF and CRP levels.<br><br>CONCLUSION: COVID arthritis is a complication of long COVID that affects both men and women, with persistent elevation of inflammatory biomarkers. While levels decreased during the follow-up period, extended monitoring is necessary to determine the duration required for normalization. Further research is warranted to understand the long-term implications of these findings.},
}
@article {pmid41536833,
year = {2025},
author = {Amput, P and Wongphon, S},
title = {Comparison of physical fitness in youth with post-COVID-19: A study of individuals with and without symptoms.},
journal = {AIMS public health},
volume = {12},
number = {4},
pages = {1026-1034},
pmid = {41536833},
issn = {2327-8994},
abstract = {This study aims to examine differences in physical fitness among young adults in three distinct groups: individuals with long COVID, those who had recovered from COVID-19 without lingering symptoms, and healthy individuals with no history of infection. A total of 105 participants were equally divided into the three groups (n = 35 each). Evaluations included handgrip strength for upper body strength, handheld dynamometry for quadricep strength, and a six-minute walk test (6MWT) to assess the cardiorespiratory performance. Participants with long COVID demonstrated significantly lower handgrip strengths compared to the control group. Additionally, both post-COVID groups showed reduced 6MWT distances and elevated post-exercise physiological responses, including heart rate, systolic blood pressure, perceived exertion, and leg fatigue, regardless of symptom persistence. These findings indicate that individuals recovering from COVID-19, especially those with persistent symptoms, exhibit measurable declines in muscular and cardiorespiratory fitness, along with heightened physiological stress during physical activity.},
}
@article {pmid41536211,
year = {2026},
author = {Linnhoff, S and Cohen Kadosh, R and Zaehle, T},
title = {EEG-based frontal excitation/inhibition balance as an objective biomarker for cognitive fatigue across multiple sclerosis and Long COVID.},
journal = {Psychological medicine},
volume = {56},
number = {},
pages = {e21},
doi = {10.1017/S0033291725103024},
pmid = {41536211},
issn = {1469-8978},
support = {539530253//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; Male ; Female ; *Multiple Sclerosis/complications/physiopathology ; *COVID-19/complications/physiopathology ; Adult ; Cross-Sectional Studies ; *Electroencephalography ; Middle Aged ; *Fatigue/physiopathology/etiology/diagnosis ; Biomarkers ; },
abstract = {BACKGROUND: Cognitive fatigue is a prevalent and disabling symptom in neurological and post-viral conditions, including multiple sclerosis (MS) and Long COVID. Assessment relies largely on self-report, and no validated objective biomarker exists, limiting reliable diagnosis and treatment monitoring. The aperiodic exponent of the Electroencephalogram (EEG) power spectrum, reflecting the excitation/inhibition (E/I) balance, is a promising candidate biomarker. We examined whether aperiodic exponent values can objectively identify pathological fatigue and assessed their classification accuracy.<br><br>METHODS: We conducted a cross-sectional study, including 119 participants: 36 healthy controls, 33 with Long COVID-related fatigue (LCOF), and 50 with MS (23 fatigued and 27 nonfatigued). Resting-state EEGs were analyzed, and associations with fatigue ratings and group differences were assessed. Logistic mixed-effects regression models evaluated classification accuracy for fatigue status.<br><br>RESULTS: Lower frontal aperiodic exponents were associated with higher cognitive fatigue across participants. Fatigued individuals, regardless of diagnosis, showed reduced frontal exponent values compared with nonfatigued groups, while no differences emerged in occipital regions. Logistic regression confirmed that frontal exponent values significantly predicted fatigue status, improving classification accuracy beyond age and depression, with good sensitivity and specificity.<br><br>CONCLUSIONS: The frontal aperiodic exponent is a regionally specific biomarker of cognitive fatigue across MS and LCOF. Mechanistic interpretation suggests an altered prefrontal E/I balance, which could inform the development of targeted interventions to alleviate cognitive fatigue. It offers a clinically accessible tool to complement self-report, support trial stratification, and enable objective treatment monitoring. Importantly, its presence across distinct disorders highlights its value as a transdiagnostic marker of fatigue.},
}
@article {pmid41535956,
year = {2026},
author = {Zhang, Y and Al-Hakeim, HK and Al-Jassas, HK and Maes, M},
title = {The NLRP3 inflammasome as a key pathway in the affective and chronic fatigue symptoms of Long COVID.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {166},
pmid = {41535956},
issn = {1479-5876},
abstract = {BACKGROUND: The neuropsychiatric and somatic manifestations (physio-affective phenome) of Long COVID are substantially predicted by elevated peak body temperature (PBT) and diminished oxygen saturation (SpO2) during the acute infectious stage. The latter is linked to the immune pathophysiology of Long COVID involving activation of the immune-inflammatory response system (IRS) and the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome. Nevertheless, there is a lack of data indicating whether NLRP3 and its components are implicated in the physio-affective phenome of Long COVID.<br><br>METHOD: We enrolled 161 Long COVID patients 6 to 9 months after the acute phase and divided them into two groups based on their baseline PBT and SpO2 levels, corresponding to mild and severe acute COVID-19. We assessed serum NLRP3, caspase-1, C-reactive protein (CRP), interleukin (IL)-18, IL-1&#x3b2;, IL-10, fibronectin, and Gasdermin D (GSDMD) during Long COVID.<br><br>RESULTS: All of the aforementioned indicators (except IL-10) were substantially higher in Long COVID patients who had previously experienced severe COVID-19 than in those who had mild acute COVID-19. The physio-affective phenome of Long COVID and the severity of the acute COVID-19 were significantly correlated with these IRS biomarkers, with the exception of fibronectin. The variance in the overall severity of Long COVID is accounted for (49.5%) by the combined influence of fibronectin, IL-10, SpO2, and PBT.<br><br>CONCLUSION: The severity of Long COVID is strongly associated with IRS and NLRP3 activation and the severity of the inflammatory response during the acute infectious phase. NLRP3 activation is a drug target to treat Long COVID.},
}
@article {pmid41535626,
year = {2026},
author = {Kumar, S and Li, C and Zhou, L and Zhan, Q and Alaswad, A and Volland, S and Costa, B and Krooss, SA and Klefenz, I and Schmaus, H and Zeuzem, A and von Witzendorff, D and Lickei, H and Pueschel, L and Kraft, ARM and Cornberg, M and Koczulla, AR and Pink, I and Hoeper, MM and Xu, CJ and Häussler, S and Wiestler, M and Netea, MG and Illig, T and Sun, J and Li, Y},
title = {A distinct monocyte transcriptional state links systemic immune dysregulation to pulmonary impairment in long COVID.},
journal = {Nature immunology},
volume = {27},
number = {2},
pages = {200-212},
pmid = {41535626},
issn = {1529-2916},
support = {R01 AG090337/AG/NIA NIH HHS/United States ; 01EQ2302A, 031L0318A, ZN4257//Bundesministerium f&#xfc;r Bildung und Forschung (Federal Ministry of Education and Research)/ ; R01 AG069264/AG/NIA NIH HHS/United States ; 14-76403-184//Nieders&#xe4;chsische Ministerium f&#xfc;r Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)/ ; R01 AI147394/AI/NIAID NIH HHS/United States ; R01 HL170961/HL/NHLBI NIH HHS/United States ; AG069264, AI147394, HL170961, AI176171, AG090337//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; 948207//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; R01 AI176171/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Monocytes/immunology/metabolism ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; Male ; Female ; Middle Aged ; Aged ; Adult ; Single-Cell Analysis ; },
abstract = {The mechanisms driving immune dysregulation in long COVID disease remain elusive. Here we integrated single-cell multiome data, immunological profiling and functional assays to investigate immune alterations across multiple cohorts. A transcriptional state in circulating monocytes (LC-Mo) was enriched in individuals with mild-moderate acute infection and accompanied by persistent elevations of plasma CCL2, CXCL11 and TNF. LC-Mo showed TGFβ and WNT-β-catenin signaling and correlated with fatigue severity. Protein markers of LC-Mo were increased in individuals with pronounced fatigue or dyspnea, and those with severe respiratory symptoms showed higher LC-Mo expression. Epigenetically, LC-Mo exhibited AP-1- and NF-κB1-driven profibrotic programs. LC-Mo-like macrophages in bronchoalveolar lavage samples from individuals with severe respiratory symptoms displayed a profibrotic profile, and individuals with a high LC-Mo transcriptional state showed impaired interferon responses after stimulation. Collectively, our findings define a pathogenic monocyte transcriptional state linking systemic immune dysfunction to persistent long COVID disease, providing mechanistic insights and potential therapeutic targets.},
}
@article {pmid41535625,
year = {2026},
author = {Antar, AAR and Pasetes, EC and Brennon, KMZ and Cox, AL},
title = {Immunologically distinct long COVID after mild acute disease.},
journal = {Nature immunology},
volume = {27},
number = {2},
pages = {173-174},
pmid = {41535625},
issn = {1529-2916},
}
@article {pmid41535076,
year = {2026},
author = {Prashar, J and Hillman, T and Wall, EC and Sarna, A and Mi, E and Bell, R and Sahota, J and Zandi, M and McNamara, P and Livingston, R and Gore, R and Lunken, C and Bax, E and Nyam, R and Rafie Manzelat, AM and Hishmeh, L and Attree, E and Cone, S and Banerjee, A and Heightman, M},
title = {Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis.},
journal = {BMJ open},
volume = {16},
number = {1},
pages = {e103884},
pmid = {41535076},
issn = {2044-6055},
mesh = {Humans ; Female ; *COVID-19/therapy/complications/epidemiology/physiopathology ; Male ; Middle Aged ; Prospective Studies ; Adult ; Quality of Life ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; SARS-CoV-2 ; Fatigue ; Hospitalization/statistics &amp; numerical data ; Post-Acute COVID-19 Syndrome ; Aged ; Return to Work/statistics &amp; numerical data ; },
abstract = {OBJECTIVE: To characterise long-term trajectory of recovery in individuals with long covid.<br><br>DESIGN: Prospective cohort.<br><br>SETTING: Single-centre, specialist post-COVID service (London, UK).<br><br>PARTICIPANTS: Individuals aged &#x2265;18 years with long covid (hospitalised and non-hospitalised) from April 2020 to March 2024.<br><br>MAIN OUTCOME MEASURES: Routine, prospectively collected data on symptoms, quality of life (including Fatigue Assessment Scale (FAS) and EuroQol 5 Dimensions (EQ-5D), return to work status and healthcare utilisation (investigations, outpatient and emergency attendances). The primary outcome was recovery by self-reported >75% of 'best health' (EQ-5D Visual Analogue Scale) and was assessed using Cox proportional hazards regression models over 4 years. Linked National Health Service England registry data provided secondary care healthcare utilisation and expenditure.<br><br>RESULTS: We included 3590 individuals (63.3% female, 73.5% non-hospitalised, median age 50.0 years, 71.9% with &#x2265;2 doses of COVID-19 vaccination), who were followed up for a median of 136 (0-346) days since first assessment and 502 (251-825) days since symptom onset. At first assessment, 33.2% of employed individuals were unable to work. Dominant symptoms were fatigue (78.7%), breathlessness (68.1%) and brain fog (53.5%). 33.4% of individuals recovered to >75% of best health prior to clinic discharge (recovery occurred median 202 (94-468) days from symptom onset). Vaccinated individuals were more likely to recover faster (pre: HR 2.93 (2.00-4.28) and post: HR 1.34 (1.05-1.71) COVID-19 infection), whereas recovery hazard was inversely associated with FAS (HR 0.37 (0.33-0.42)), myalgia (HR 0.59 (0.45-0.76)) and dysautonomic symptoms (HR 0.46 (0.34-0.62)). There was high secondary care healthcare utilisation (both emergency and outpatient care). Annual inpatient and outpatient expenditure was significantly lower in hospitalised individuals while under the service. When compared with the prereferral period, emergency department attendances were reduced in non-hospitalised patients with long covid, but outpatient costs increased.<br><br>CONCLUSIONS: In the largest long covid cohort from a single specialist post-COVID service to date, only one-third of individuals under follow-up achieved satisfactory recovery. Fatigue severity and COVID-19 vaccination at presentation, even after initial COVID-19 infection, was associated with long covid recovery. Ongoing service provision for this and other post-viral conditions is necessary to support care, progress treatment options and provide capacity for future pandemic preparedness. Research and clinical services should emphasise these factors as the strongest predictors of non-recovery.},
}
@article {pmid41532626,
year = {2025},
author = {Pechanova, O and Paulis, L},
title = {Nitric Oxide at the Nexus of ACE2 Biology and COVID-19: Implications for Cardiovascular and Neurodegenerative Comorbidities.},
journal = {Physiological research},
volume = {74},
number = {Suppl 2},
pages = {S171-S184},
pmid = {41532626},
issn = {1802-9973},
mesh = {Humans ; *COVID-19/metabolism/epidemiology/virology ; *Angiotensin-Converting Enzyme 2/metabolism ; *Nitric Oxide/metabolism ; *Cardiovascular Diseases/metabolism/epidemiology/virology ; *Neurodegenerative Diseases/metabolism/epidemiology/virology ; SARS-CoV-2 ; Animals ; Comorbidity ; Renin-Angiotensin System/physiology ; },
abstract = {SARS-CoV-2 engages ACE2 for cell entry, perturbing the counter-regulatory ACE2/Ang-(1-7)/Mas axis and shifting the renin angiotensin system toward ACE/Ang II/AT1 signaling, with a concomitant reduction in nitric oxide (NO) bioavailability. NO sits at the crossroads of these pathways, acting both as an antiviral modulator of spike-ACE2 interactions and as a downstream mediator of Mas-dependent endothelial protection. This review summarizes evidence on NO across three layers: (i) viral entry (S nitrosylation of spike/ACE2, protease modulation), (ii) cardiovascular comorbidities (hypertension, obesity, diabetes) where ACE2 downregulation impairs endothelial NO synthase (eNOS)-dependent NO production and promotes thrombosis and microvascular dysfunction, and (iii) neurovascular/ neurodegenerative sequelae, in which renin-angiotensin-aldosterone system (RAAS) dysregulation along with imbalance between protective eNOS/nNOS and inflammatory iNOS fosters blood-brain barrier disruption, microthrombosis, and cognitive impairment. Shared mechanisms - endotheliitis, microvascular dysfunction, and neuroinflammation may explain convergent risks for cardiac injury and cognitive decline in long COVID-19. Putative therapeutic strategies may include restoring physiological NO (via Mas agonism, Ang-(1-7), inhibition of Ang 1-7 degradation and recombinant ACE2), pulmonary-selective inhaled NO, hybrid S nitrosylated agents, and selective attenuation of iNOS/peroxynitrite alongside endothelial support. Targeted modulation - enhancing eNOS/nNOS while constraining iNOS offers a unified framework to mitigate both cardiovascular and neurodegenerative consequences of COVID-19.},
}
@article {pmid41532581,
year = {2026},
author = {Mason, TB and Dolgon-Krutolow, A and Lee, D and Knight, TK and Lee, R and Herzig, SE and Doctor, JN and Meeker, D},
title = {Ecological momentary assessment of physical symptoms among patients with a history of COVID-19 infection: towards understanding long covid and the role of mental health symptoms.},
journal = {Psychology &amp; health},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/08870446.2025.2612038},
pmid = {41532581},
issn = {1476-8321},
abstract = {OBJECTIVE: This project used ecological momentary assessment (EMA) in adults with a previous COVID-19 infection to examine the association of long covid with physical symptoms and the association of contextual factors with physical symptoms among adults with long covid.<br><br>METHOD: Adults who had been diagnosed with COVID-19 (N&#x2009;=&#x2009;121) completed survey questions about COVID-19 history, long covid and mental and physical health followed by 7-days of EMA. During EMA, participants reported on physical symptoms and contextual factors five times across the day.<br><br>RESULTS: Multilevel exploratory factor analyses found two within-subjects (i.e. aches/fatigue and respiratory symptoms) and one between-subjects physical symptom factor. Long covid was associated with more real-world aches/fatigue symptoms compared to those without long covid, and effects persisted after controlling for baseline mental health; long covid was unrelated to respiratory symptoms. Greater within-subjects aches/fatigue were concurrently associated with higher negative affect, higher interpersonal problems, and lower positive affect and prospectively associated with greater negative affect and lower positive affect.<br><br>CONCLUSION: Findings show that long covid diagnosis predicts real-world ache/fatigue symptoms, and this effect is not explained by baseline mental health. Furthermore, real-world ache/fatigue symptoms are associated with poor momentary psychosocial functioning and predict acute affective disturbance.},
}
@article {pmid41532066,
year = {2026},
author = {Feng, X and Wang, Y and Li, Y and Long, J and Liu, F and Yang, H},
title = {Application of the humanized mouse model in research into SARS-CoV-2 infection (Review).},
journal = {Medicine international},
volume = {6},
number = {1},
pages = {9},
pmid = {41532066},
issn = {2754-1304},
abstract = {The coronavirus disease 2019 (COVID-19) pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a profound impact on global public health. The complexity of its pathogenic mechanisms and host interactions urgently requires high-fidelity animal models to support research. Humanized mouse models break the species barrier through gene editing and immune reconstitution technologies, providing a key tool to simulate human infection characteristics and pathological processes. A number of studies have reported the application of humanized mouse models in the fields of COVID-19 research, such as SARS-CoV-2 pathogenesis, anti-SARS-CoV-2 drug discovery and vaccine development, etc. The present review aimed to systematically document the latest advances in the application of humanized mouse models based on different construction strategies, such as receptor humanization, immune system humanization and composite humanization. These models have not only elucidated the pathogenicity differences and immune escape mechanisms of SARS-CoV-2 variants, but have also validated the efficacy of broad-spectrum anti-SARS-CoV-2 strategies, including angiotensin-converting enzyme 2-targeted therapies, antibody cocktail regimens and mucosal vaccines. Additionally, humanized mouse models have played a pivotal role in investigating the mechanisms underlying long COVID. By revealing the multi-system pathogenic mechanisms of pulmonary fibrosis, neurodegeneration and intestinal microbiota dysregulation, these models provide a theoretical foundation for the development of targeted intervention strategies.},
}
@article {pmid41531877,
year = {2025},
author = {Finsterer, J},
title = {There is currently no evidence that long-COVID-19 leads to neurodegenerative diseases such as SDAT, amyotrophic lateral sclerosis, or Parkinson's disease.},
journal = {Brain circulation},
volume = {11},
number = {4},
pages = {354-355},
pmid = {41531877},
issn = {2455-4626},
}
@article {pmid41530768,
year = {2026},
author = {Bhéreur, A and McDuff, K and Naye, F and Lemay, L and Grenier, AD and O'Hara, ME and Nathanson, J and Lavoie, KL and Sasseville, M and Kadakia, Z and Décary, S and Munblit, D and O'Brien, KK},
title = {Rethinking measurement of health outcomes in Long COVID: complexities, challenges and considerations.},
journal = {Health and quality of life outcomes},
volume = {24},
number = {1},
pages = {8},
pmid = {41530768},
issn = {1477-7525},
abstract = {The reality of Long COVID emerged soon after the beginning of the COVID-19 pandemic. More than five years later, thousands of articles have been published with multiple case definitions, heterogenous populations, and numerous measurement instruments, yielding a massive amount of evidence. Health outcome measurement is vital for identifying health challenges, changes in health status and predicting future health states for people with Long COVID. Nevertheless, distinct issues of measurement require attention in the context of Long COVID. In this commentary, we discuss complexities, challenges and considerations associated with health outcome measurement in research and clinical practice with people with Long COVID. Specifically, we address: (i) identifying the population in the context of variable terminology, definitions and symptoms affecting people with Long COVID; (ii) identifying the complexity of health constructs, often multidimensional, to measure with numerous health-related consequences associated with Long COVID; (iii) identifying the purpose of measurement while taking into account the dynamic nature of Long COVID and (iv) identifying appropriate outcome measures used with people with Long COVID and their limitations. We highlight important considerations for measurement in research and clinical practice, including the impacts of the various symptoms and the dynamic nature of Long COVID. We provide examples of outcome measures used to date in the context of Long COVID to illustrate the complexities throughout, with a glimpse at wider consequences. We conclude with a brief discussion of considerations to help pave the way forward for the improvement in health outcomes measurement in Long COVID research and clinical practice. Advancing knowledge on Long COVID requires a return to the fundamentals of measurement science. It is critical to appropriately assess the measurement properties of existing instruments for their ability to accurately and reliably measure health-related constructs associated with this condition. Identifying limitations of currently used tools is also essential to prevent perpetuation of issues in the development of condition-specific measurement instruments for Long COVID. This, in turn, will help pave the way for more robust measurement and improved data interpretation in the context of Long COVID.},
}
@article {pmid41529159,
year = {2026},
author = {Berkowitz, J and Lu, F and DeAngelis, J and Simmons, J and Wu, WC},
title = {Comparative Efficacy of Pulmonary Rehabilitation in Patients With COPD, ILD, and Long COVID: PHYSICAL AND PSYCHOSOCIAL OUTCOMES.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {},
number = {},
pages = {},
pmid = {41529159},
issn = {1932-751X},
abstract = {INTRODUCTION: The benefits of pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) are well-established, but data on the relative efficacy of PR in patients with interstitial lung disease (ILD) and prolonged symptoms from coronavirus disease-2019 (Long COVID) remain limited. With the increasing prevalence of Long COVID, understanding the role of PR in this group is essential.<br><br>METHODS: Records of patients enrolled in PR between September 1, 2020, to November 30, 2022, at an academic health system were analyzed. Patients were categorized into COPD, ILD, and Long COVID groups based on primary referral diagnosis. Outcome measures included 6-minute walk test distance, COPD Assessment Tool, Modified Medical Research Council Questionnaire, and psychosocial assessments. Mixed-linear modeling for repeated measures compared pre- and post-PR outcomes within and across groups by referral diagnosis while adjusting for baseline covariates.<br><br>RESULTS: Of the 316 patients enrolled in PR, 192 completed PR. Demographics were similar across groups, though patients with Long COVID were younger, more likely to be Hispanic, and have higher body mass index than patients referred for COPD. Significant improvements were observed in functional capacity, dyspnea, quality of life, depression, anxiety, and stress in all 3 groups following PR without significant between-group differences in PR outcomes.<br><br>DISCUSSION: This single-center analysis suggests that PR was associated with significantly improved physical and psychosocial well-being in patients with COPD, ILD, and Long COVID with comparable outcomes across all groups. Future randomized-controlled trials are needed to confirm the benefits of PR for patients with Long COVID.},
}
@article {pmid41528554,
year = {2026},
author = {Wilkey, HL and Datta, BK},
title = {Family history of cancer as a risk factor for Long COVID among United States adults.},
journal = {Cancer causes &amp; control : CCC},
volume = {37},
number = {1},
pages = {17},
pmid = {41528554},
issn = {1573-7225},
mesh = {Humans ; Female ; *Neoplasms/epidemiology/genetics ; Male ; *COVID-19/epidemiology/virology ; United States/epidemiology ; Middle Aged ; Adult ; Risk Factors ; Cross-Sectional Studies ; Prevalence ; Aged ; SARS-CoV-2 ; Young Adult ; Health Surveys ; },
abstract = {BACKGROUND: Previous research has identified several risk factors for Long COVID, including cancer. This study aims to assess whether adults with a family history of cancer had a higher risk for Long COVID.<br><br>METHODS: This cross-sectional study used data on 25,389 adults, who were not cancer patients or survivors, from the nationally representative 2023 National Health Interview Survey. Multivariable generalized linear models were estimated to assess the prevalence of Long COVID (i.e., having symptoms for&#x2009;&#x2265;&#x2009;3&#xa0;months) for self-reported family history of cancer by sequentially adjusting for demographic and socioeconomic attributes, health behaviors, and underlying health conditions. Karlson-Holm-Breen (KHB) method was applied to assess potential mediating effects of health conditions.<br><br>RESULTS: Long COVID prevalence in the study population was 8.4%. Adults with a family history of cancer were 1.26 (95% CI 1.15-1.38) times more likely to have Long COVID. The prevalence rate ratio decreased to 1.19 (95% CI 1.08-1.28) when health conditions were accounted for. KHB decomposition suggested that 30.16% of the association was mediated through underlying health conditions.<br><br>CONCLUSION: These findings suggest that familial or genetic factors associated with cancer susceptibility may also contribute to Long COVID risk. Further research is needed to explore potential biological mechanisms underlying this association.},
}
@article {pmid41527930,
year = {2026},
author = {Fernandes, TP and Santos, NA and Dahlgren, LN},
title = {Prospective study of long COVID-related psychological and biological outcomes in individuals with tobacco use disorder.},
journal = {Journal of addictive diseases},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/10550887.2025.2609140},
pmid = {41527930},
issn = {1545-0848},
abstract = {BACKGROUND: Individuals with tobacco use disorder (TUD) may be particularly vulnerable to the challenges following long COVID.<br><br>OBJECTIVE: This study assessed whether individuals with TUD and no prior neuropsychiatric conditions developed new symptoms following long COVID-19 infection.<br><br>METHODS: A cohort of 104 adults with TUD&#xa0;completed psychological and biological assessments before the COVID-19 pandemic and were reevaluated four months post-long COVID diagnosis. Evaluations covered mood symptoms, sleep, perceived stress, quality of life, and serum cortisol.<br><br>RESULTS: The participants exhibited marked increases in depressive symptoms, anxiety, insomnia, and perceived stress, accompanied by significant declines in sleep quality and quality of life (all p-values < 0.001). Serum cortisol levels decreased significantly, indicating altered HPA axis activity.<br><br>CONCLUSION: This study suggests that long COVID may disproportionately influence addictive disorders, not only by exacerbating existing vulnerabilities, but potentially contributing to the onset of new mental health challenges.},
}
@article {pmid41527239,
year = {2026},
author = {Goldschmidt, MI and Torensma, M and Beune, E and Agyemang, C and Rostila, M and Benfield, T and Norredam, M and Moseholm, E},
title = {Experiences of access to care, diagnosis and rehabilitation among a multiethnic patient population with long COVID in Denmark: A qualitative study.},
journal = {Scandinavian journal of public health},
volume = {},
number = {},
pages = {14034948251400105},
doi = {10.1177/14034948251400105},
pmid = {41527239},
issn = {1651-1905},
abstract = {AIMS: Several studies suggest that ethnic minorities are at higher risk of experiencing long COVID compared to majority populations. This study aimed to qualitatively explore the experiences of accessing care, diagnosis and rehabilitation among patients with long COVID in a multiethnic population in Denmark.<br><br>METHODS: We carried out 18 semi-structured interviews with individuals of Danish, Turkish and Moroccan background who were diagnosed with long COVID. Informants were sampled purposively to secure variation in sex, age, country of origin and immigration status. Our interview guide was developed using the theoretical framework of candidacy. Interviews were transcribed verbatim, member checked and subsequently analyzed using thematic framework analysis and NVivo software.<br><br>RESULTS: Our findings show that accessing care and rehabilitation for long COVID was difficult regardless of ethnic background. Following the novelty of COVID-19 and thus uncertainty of long COVID, informants had to self-advocate and navigate established and alternative healthcare services by themselves. Additionally, patients with Moroccan and Turkish minority background had to contend with experiences of differential treatment and of having their motives for seeking help questioned, while also finding it harder to benefit from the rehabilitation measures offered.<br><br>CONCLUSIONS: Our study demonstrates how the emergence of a new viral disease with unknown long-term sequelae resulted in a group of patients who largely carried the burden of getting better by themselves. Yet patients with an ethnic minority background experienced additional, worrying barriers. More research into relevant diagnosis, care and support for all long COVID patients is needed, especially among ethnic minorities.},
}
@article {pmid41527037,
year = {2026},
author = {Lange-Tal, T and Tuvia, N and Lazar, S and Farajh, Y and Bernstine, T and Abassi, Z and Edelstein, M and Jabal, KA},
title = {Is long-term disruption of the renin-angiotensin-aldosterone system associated with long COVID? A retrospective cohort study among healthcare workers.},
journal = {BMC infectious diseases},
volume = {26},
number = {1},
pages = {300},
pmid = {41527037},
issn = {1471-2334},
abstract = {BACKGROUND: Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin aldosterone system (RAAS), is the main receptor for SARS-CoV-2 entry into human cells. The occurrence of long-term symptoms post-COVID 19 infection (Long COVID, LC) is an important public health issue with an unclear etiological mechanism. We aimed to determine whether LC was associated with long-term RAAS disruption.<br><br>METHODS: We recruited a cohort of healthcare workers (HCWs) from Ziv Medical Center in Safed, Israel, who were uninfected and unvaccinated at baseline, and who later became infected with SARS-CoV-2. We measured serum circulating levels of four RAAS components (ACE, ACE2, Ang1-7 and AngII) using commercially available ELISA assays at three time points, using serum samples regularly collected from consenting hospital workers during the COVID-19 pandemic: pre-infection, 3&#x2013;6 months post-infection, and a year post-infection. Post-serum collection we determined LC status using an online survey based on self-reported, LC-compatible symptoms not explained by alternative diagnoses. We excluded participants with conditions or medications interfering with the RAAS (e.g. hypertension, chronic kidney disease, antihypertensives, antidiuretics). At each time point we compared the levels of each of the four RAAS components between those infected and reporting LC and those infected not reporting LC using Mann Whitney U tests and Wilcoxon signed-rank tests, corrected for multiple testing.<br><br>RESULTS: We included 38 LC positive and 38 LC negative participants. Age/gender distribution was similar in both groups. No statistically significant differences in any of the four RAAS markers were observed between LC cases and controls at either 3&#x2013;6 months or 12 months post-infection in our study sample.<br><br>CONCLUSION: No evidence was detected within the limits of the study design and sample size to conclude that long-term disruption of RAAS is a significant contributor to LC pathophysiology.<br><br>CLINICAL TRIAL: Not applicable.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-026-12527-z.},
}
@article {pmid41523874,
year = {2025},
author = {Jarrar, T and Halaseh, N and Doudin, D and Bael, P and Shaheen, A and Jobeh, E and Sada, AA and Awwad, AA and Alqtishat, B and Hallak, H},
title = {Long-Term Self-Reported Symptoms Among Adults After COVID-19 Infection in the West Bank: A Cross-Sectional Analysis.},
journal = {Global health, epidemiology and genomics},
volume = {2025},
number = {},
pages = {2867843},
pmid = {41523874},
issn = {2054-4200},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Male ; Adult ; Cross-Sectional Studies ; *Self Report ; Middle Aged ; SARS-CoV-2 ; Hospitalization/statistics &amp; numerical data ; Middle East/epidemiology ; Fatigue/epidemiology ; Prevalence ; },
abstract = {INTRODUCTION: With growing recognition of the prolonged effects of COVID-19, there is an urgent need to understand its extended clinical and public health implications across diverse settings. Long-term consequences following SARS-CoV-2 infection remain insufficiently studied in Middle Eastern populations. This study aimed to assess the prevalence of persistent COVID-19 symptoms among Palestinian adults and to evaluate their associations with hospitalization and recovery duration.<br><br>METHODS: This cross-sectional study was conducted on a randomized sample of 407 adult COVID-19 patients confirmed by the Palestinian Ministry of Health between November 25 and December 15, 2020. We used a standardized Arabic questionnaire to cover demographics, medical history, symptoms, complications, and physical activity. Data were gathered by phone interviews in October 2021. All data came from self-reports. With significance defined at p&#x2009;<&#x2009;0.05, associations between the symptom duration, hospitalization, and recovery time were examined using descriptive statistics and chi-square tests.<br><br>RESULTS: The study population had a mean age of 40&#x2009;years; 54% were female, and 70.3% had no previous medical history. Common complaints were fatigue (64.9%), anosmia (61.9%), joint pain (52.6%), and headache (51.8%). Hospitalization was necessary in 7.6% of patients, while 5.9% required oxygen or intubation. Most patients (92.6%) recovered in 4&#x2009;months. The persistence of chest pain (&#x3c7; [2], 16.225), shortness of breath (&#x3c7; [2], 13.257), and lethargy (&#x3c7; [2], 8.194) was significantly associated with hospitalization (p < 0.001). The persistence of the previously mentioned symptoms was significantly associated with the duration of recovery.<br><br>CONCLUSION: This study offers valuable insights into the long-term symptoms experienced by individuals recovering from COVID-19 in the West Bank. The findings carry implications for clinicians, public health authorities, and affected individuals, highlighting the importance of integrated care strategies and sustained support throughout the postacute phase of the disease.},
}
@article {pmid41523768,
year = {2025},
author = {Silvestri, C and Stasi, C and Profili, F and Bartolacci, S and Sessa, E and Tacconi, D and Villari, L and Carrozzi, L and Dotta, F and Bargagli, E and Donnini, S and Masotti, L and Rasero, L and Lavorini, F and Pistelli, F and Chimera, D and Sorano, A and D'alessandro, M and Pacifici, M and Milli, C and Voller, F},
title = {Evaluation of short and long-term laboratory and instrumental findings in COVID-19 patients hospitalized in Tuscany.},
journal = {World journal of experimental medicine},
volume = {15},
number = {3},
pages = {107220},
pmid = {41523768},
issn = {2220-315X},
abstract = {BACKGROUND: The World Health Organization defined long coronavirus disease 2019 (COVID-19) as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 infection, with these symptoms lasting for at least 2 months with no other explanation.<br><br>AIM: To evaluate the potential laboratory and instrumental findings (short-term and long-term) resulting from COVID-19.<br><br>METHODS: This longitudinal observational COVID-19 cohort study (March 1, 2020-March 1, 2021) was carried out on patients &#x2265; 18 years old who were admitted to the University Hospitals of Pisa, Siena and Careggi and the Azienda USL Toscana Nord Ovest, Sud Est and USL Centro Toscana and were subjected to follow-up. Follow-up was conducted between 0 day and 89 days, 90 days and 179 days, 180 days and 269 days, 270 days and 359 days, and more than 360 days after hospitalization.<br><br>RESULTS: Of 2887 patients (58.5% males, average age 66.2 years) hospitalized in the study period (March 1, 2020-March 1, 2021) carrying out at least one follow-up examination within 12 months of discharge, a total of 1739 patients (705 males, average age 66 years) underwent laboratory tests, of whom 714 patients (470 males, average age 63 years) underwent spirometry. Some laboratory test results remained above the threshold even at follow-up beyond 360 days (C-reactive protein: 36%, fibrin degradation fragment: 48.8%, gamma-glutamyl transferase: 16.8%), while others showed a return to normal range more quickly in almost all patients. Alterations in liver enzymes, hematocrit, hemoglobin, lymphocytes and neutrophils were associated with the risk of requiring oxygen therapy or forced expiratory volume in one second/forced vital capacity alterations at follow-up.<br><br>CONCLUSION: Alterations in liver enzymes, hematocrit or hemoglobin, lymphocytes and neutrophils were associated with risk outcomes (need for oxygen therapy or spirometry alterations). These imbalanced conditions may contribute to pulmonary dysfunction.},
}
@article {pmid41523623,
year = {2025},
author = {Kim, GJ and Alam, MA and Crabtree, JS and Rose, R and Lamers, SL and Chu, S and Horswell, R and Fort, D and Miele, L},
title = {Long COVID incidence across SARS-CoV-2 lineages and identification of conserved spike targets for multivalent vaccines.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e288},
pmid = {41523623},
issn = {2059-8661},
abstract = {BACKGROUND: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets.<br><br>METHOD: To estimate Long COVID incidence across variants, we linked 4789 SARS-CoV-2 sequences to 3090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) based definitions of Long COVID presentation developed by the N3C consortium.<br><br>RESULTS: 1,554 patients (1,536 Long COVID-negative) met Long COVID definitions, with 56.3% being female, 36.1% self-reported as African American, 5.5% self-reported as Hispanic/Latino, and 54.5% had received at least one vaccine dose 14 days prior to SARS-CoV-2 collection. Long COVID-positive patients were older (mean age 43.1 years) than negative patients (35.9 years; p = 0.0054) and were more likely to be female (p = 0.0001). Among unvaccinated patients, those with Long COVID were significantly younger than their vaccinated counterparts (p < 0.00001). Long COVID incidence varied by PANGO lineage, ranging between 14% in AY.13 to 67.8% in B.1.1.7. Analysis of spike protein diversity revealed eight conserved amino acid regions (Shannon entropy < 0.43), representing potential targets for vaccine design.<br><br>CONCLUSION: Long COVID rates across thousands of annotated SARS-CoV-2 sequences revealed lineage-specific risk and conserved epitopes for future interventions.},
}
@article {pmid41523183,
year = {2026},
author = {Rudroff, T},
title = {Neurological diversity and generalizability: building on AMPA receptor imaging advances in long COVID.},
journal = {Brain communications},
volume = {8},
number = {1},
pages = {fcaf499},
pmid = {41523183},
issn = {2632-1297},
abstract = {This scientific commentary refers to 'Systemic increase of AMPA receptors associated with cognitive impairment of long COVID' by Fujimoto et al. (https://doi.org/10.1093/braincomms/fcaf337).},
}
@article {pmid41522693,
year = {2026},
author = {Shahbaz, S and Rahmati, A and Syed, H and Elahi, S},
title = {Soluble CD14 promotes Th17 expansion and differentiation through gamma-aminobutyric acid and expands infidel innate lymphoid cells.},
journal = {PNAS nexus},
volume = {5},
number = {1},
pages = {pgaf406},
pmid = {41522693},
issn = {2752-6542},
abstract = {Interleukin-17 (IL-17) plays a central role in the pathogenesis of various autoimmune diseases. Soluble CD14 (sCD14), a marker of innate immune activation, is elevated in several inflammatory conditions. However, its influence on IL-17 production and the differentiation of Th17 cells remains poorly understood. We found that sCD14 enhances Th17-associated cytokine production and up-regulates critical transcription factors such as STAT3 and RORC. Notably, sCD14's effect on Th17 polarization was mediated indirectly through autologous sCD14-treated peripheral blood mononuclear cell (PBMC) supernatant (sCD14-PBMC-Sup). Additionally, we identified a distinct cytokine profile enriched for pro-inflammatory cytokines and chemokines in sCD14-treated T cells, further reinforcing the Th17-promoting role of sCD14. Interestingly, gamma-aminobutyric acid (GABA), a metabolite elevated in sCD14-treated monocytes, was identified as a potential contributor to Th17 polarization. GABA supplementation in T-cell cultures enhanced IL-17A secretion, indicating its role as a signaling molecule in T-cell differentiation. Our findings also revealed the expansion of innate lymphoid cell (ILC)2/3-like cells in T-cell cultures exposed to sCD14-PBMC-Sup and GABA, highlighting the potential role of monocytes in Th17-mediated immunity. Furthermore, while sCD14 promoted Th17 polarization, it simultaneously impaired T-cell activation and proliferation, suggesting an immunosuppressive effect mediated by soluble factors released from monocytes. These results underscore the dual role of sCD14 in modulating T-cell responses, promoting Th17 differentiation while suppressing T-cell effector functions. This study identifies a previously unrecognized role for sCD14 in promoting Th17 induction, highlighting its contribution to immune regulation and its potential as a therapeutic target in Th17-driven autoimmune conditions. Classification: Immunology.},
}
@article {pmid41521322,
year = {2026},
author = {Lank, GK and Budhiraja, S and Gaelen, JI and Mukherjee, S and Singer, T and Venkatesh, A and Jimenez, M and Miller, J and Lopez, M and Duax, CJ and Blahnik, D and King, D and Hanson, BA and Bawa, AP and Bharadwaj, S and Batra, A and Liotta, EM and Koralnik, IJ},
title = {Characterizing Neuro-PASC outcome with the mobile Neuro-COVID recovery care companion application.},
journal = {BMC neurology},
volume = {26},
number = {1},
pages = {24},
pmid = {41521322},
issn = {1471-2377},
mesh = {Humans ; *COVID-19/complications ; Female ; Male ; Middle Aged ; *Mobile Applications ; Aged ; Adult ; Quality of Life ; Patient Reported Outcome Measures ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Surveys and Questionnaires ; *Nervous System Diseases/etiology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects 14 million people in the US. Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating. However, the evolution of these symptoms and factors associated with recovery are poorly understood. This study aimed to characterize Neuro-PASC symptom evolution using a mobile phone application and assess user experience.<br><br>METHODS: The Neuro-COVID Recovery Care Companion (NCRCC) mobile application consists of questionnaires integrated within Northwestern Medicine's online MyChart platform which interfaces with the electronic medical record. Neuro-PASC patients completed daily surveys of twelve Neuro-PASC symptoms and their perceived percent recovery compared to their pre-COVID baseline. Patients also completed Patient-Reported Outcomes Measurement Information System (PROMIS) quality-of-life (QoL) surveys and NIH toolbox cognitive assessments at baseline and at 3-month follow up. Participants were retrospectively classified as "Improvers" or "Non-Improvers" based on the slope and range of their percent subjective recovery.<br><br>RESULTS: Data from 63 participants presenting an average of 12.7&#xa0;months after symptom onset were analyzed, including 27 (42.9%) Improvers and 36 (57.1%) Non-Improvers. Fewer women were Improvers (50% vs 75.7%; p&#x2009;=&#x2009;0.04). Multiple correspondence analysis showed that patients presenting with a constellation of anosmia, dysgeusia, and a lack of insomnia (p&#x2009;=&#x2009;0.023) were less likely Improvers. Improvers had more fluctuations in their subjective recovery than Non-Improvers with greater mean variance (7.01 vs 3.79; p&#x2009;=&#x2009;0.0004) and positive recovery slope (5.84 vs 0; p&#x2009;<&#x2009;0.0001). There were no differences in QoL and cognition at initial assessment, but Improvers showed a trend toward increased processing speed and decreased sleep disturbance after 3&#xa0;months. Both groups found the NCRCC application easy-to-use, useful, and satisfactory.<br><br>CONCLUSIONS: Our findings reveal previously unrecognized fluctuations in subjective recovery of Neuro-PASC, and that women and patients presenting with anosmia and dysgeusia are less likely to improve one year from COVID-19 onset. We found broad alterations in QoL in both groups suggesting that strategies to reduce sleep disturbance and improve cognition may contribute to subjective improvement. Our results suggest similar mobile applications may benefit patients with other ill-defined chronic diseases, by equipping and empowering them on their often windy road to recovery.},
}
@article {pmid41520775,
year = {2026},
author = {Seo, G and Joo, H and Song, K and Kim, M and Jung, EJ and Kim, ES and Ko, JH and Lee, JS and Song, JY and Seo, JW and Choi, JY and Kwon, KT and Lee, SS and Park, WB and Choi, WS and Baek, YJ and Kim, YK and Jeong, HW and Jung, J and Lee, J},
title = {Static and dynamic scoring systems for post-acute sequelae of SARS-CoV-2 in a Korean Cohort.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {164},
number = {},
pages = {108378},
doi = {10.1016/j.ijid.2026.108378},
pmid = {41520775},
issn = {1878-3511},
abstract = {OBJECTIVES: Persistent symptoms after SARS-CoV-2 infection (PASC, long COVID) remain a major public-health concern. We developed a data-driven definition and static and dynamic PASC scoring systems in a multicenter, prospective-retrospective observational cohort across 12 South Korean institutions.<br><br>METHODS: Adults enrolled December 2022-March 2025 were followed up to 24 months; 8761 were recruited (7208 infected; 1553 controls) and 4668 met analysis criteria (4388 infected; 280 controls). Using participant-reported symptoms, surveys, and laboratory data, we identified nine symptoms robustly associated with PASC, with anosmia/ageusia and fatigue most influential.<br><br>RESULTS: A static score integrating indicators observed within 24 months yielded an optimal threshold of 13, classifying 19% of infected participants and 4% of controls as PASC positive. A dynamic score tracking six-month intervals showed symptom burdens peaking at 0-5 months post-infection and declining thereafter; at the same threshold, 33% of infected participants were classified as PASC positive, reflecting temporal fluctuation.<br><br>CONCLUSION: These data establish a quantitative definition of PASC and introduce a dynamic scoring framework to identify and monitor PASC, supporting future clinical research and practice.},
}
@article {pmid41520672,
year = {2026},
author = {Carazo, S and Skowronski, DM and Ouakki, M and De Serres, G},
title = {Methodological considerations in the attribution of long COVID to first or second infection.},
journal = {The Lancet. Infectious diseases},
volume = {26},
number = {3},
pages = {e139-e140},
doi = {10.1016/S1473-3099(25)00775-3},
pmid = {41520672},
issn = {1474-4457},
}
@article {pmid41520671,
year = {2026},
author = {Zhang, B and Wu, Q and Jhaveri, R and Forrest, CB and Chen, Y},
title = {Methodological considerations in the attribution of long COVID to first or second infection - Authors' reply.},
journal = {The Lancet. Infectious diseases},
volume = {26},
number = {3},
pages = {e141},
doi = {10.1016/S1473-3099(25)00776-5},
pmid = {41520671},
issn = {1474-4457},
}
@article {pmid41518079,
year = {2026},
author = {Lorenz, P and Steinbeck, F and Fricke, F and Mai, F and Bergmann-Ewert, W and Wossidlo, C and Reisinger, EC and Müller-Hilke, B},
title = {Patients Suffering From Post-COVID-19 Syndrome Feature Enhanced Antibody Reactivity Towards Specific Linear Epitopes Within EBV EBNA1.},
journal = {Scandinavian journal of immunology},
volume = {103},
number = {1},
pages = {e70088},
pmid = {41518079},
issn = {1365-3083},
support = {Sonderverm&#xf6;gen MV Schutzfonds//Ministry of Science, Culture, Federal and European Affairs/ ; S&#xe4;ule Gesundhei GW-20-0004//Ministry of Science, Culture, Federal and European Affairs/ ; COVICare-M-V: ZMII2-2524FSB031//German Bundestag by the German government/ ; },
mesh = {Humans ; *Epstein-Barr Virus Nuclear Antigens/immunology ; *COVID-19/immunology/complications ; Male ; Female ; *Antibodies, Viral/immunology/blood ; *SARS-CoV-2/immunology ; Adult ; *Herpesvirus 4, Human/immunology ; Autoantibodies/immunology/blood ; Retrospective Studies ; Immunoglobulin G/immunology/blood ; Middle Aged ; Cross-Sectional Studies ; *Epitopes/immunology ; Epstein-Barr Virus Infections/immunology ; Immunity, Humoral ; Aged ; },
abstract = {Post-COVID-19 syndrome (PCS; also known as post-acute sequelae of COVID-19, PASC and Long COVID) manifests with various clinical symptoms of unclear aetiology that persist or develop months after acute infection with SARS-CoV-2. Potential triggers for PCS include reactivation of latent viruses and autoimmune reactions. In our retrospective cross-sectional and explorative study we compared 48 PCS patients with 48 individuals that recovered fully from COVID-19 (convalescents, CC). We focused on characterising humoral immunity by recording IgG antibody reactivity patterns against Epstein-Barr virus (EBV) EBNA1 antigen using peptide microarray and ELISA methodology as well as determining the presence of autoantibodies. The overall binding landscape of IgG antibodies for the EBV EBNA1 protein was similar for the patients with sequelae versus the convalescents. However, the PCS patients displayed stronger reactivity for epitopes contained within the glycine-alanine repeat region of EBNA1, in particular residues 90-325, and within the central part, amino acids 393-420. Intriguingly, in the latter case, the EBNA1 peptide (residues 405-419) that discriminated the PCS and CC cohorts was localised in a different segment C-terminal from the sequence proposed to be mechanistically associated with multiple sclerosis. The screening for autoantibodies against nuclear/cytoplasmic antigens in HEp-2 cells and against CRYAB, cardiolipin, beta-2-glycoprotein I, IFN-alpha2, IFN-omega, and IL-15 antigens did neither reveal higher prevalence nor increased reactivity in the PCS patients compared to the convalescents. In conclusion, elevated antibody levels against linear peptides derived from residues 90-325 and 405-419 of EBV EBNA1 were the most distinctive characteristics in our cohort of post-COVID-19 syndrome patients.},
}
@article {pmid41517604,
year = {2026},
author = {Domanyi, R and Maitz, E and Andrianakis, A},
title = {Association Between Obesity and Post-COVID-19 Condition in Military Conscripts.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41517604},
issn = {2077-0383},
abstract = {Objectives: Obesity has been suggested as a possible risk factor for the post-COVID-19 condition, but most studies rely only on body mass index (BMI), which does not reflect body fat distribution. Waist-to-height ratio (WHtR) is a simple anthropometric indicator of central obesity and a practical proxy for body fat distribution, yet it has not been studied in relation to the post-COVID-19 condition. This study aimed to examine whether obesity, measured by BMI and WHtR, is associated with the post-COVID-19 condition. Methods: A total of 500 male military conscripts (aged 18 years) underwent anthropometric measurements (height, weight, and waist circumference). Participants with prior COVID-19 were asked whether they had persistent or new symptoms after infection. BMI categories followed WHO definitions, and WHtR ≥ 0.50 was used to define central obesity. Results: Of the 376 participants who had previously experienced COVID-19, 82 (21%) experienced the post-COVID-19 condition. Obesity (BMI ≥ 30) was more common among those with the post-COVID-19 condition than those without (15% vs. 5%). BMI-defined obesity was associated with higher odds of the post-COVID-19 condition (OR 2.80, 95%CI 1.25-6.24). Central obesity was also more frequent in the post-COVID-19 condition (26% vs. 14%) and was linked to increased odds as well (OR 2.18, 95% CI 1.20-3.97). Conclusions: Both BMI-defined obesity and central obesity were associated with the post-COVID-19 condition. While WHtR does not directly quantify body fat distribution, it represents a simple and feasible anthropometric indicator. Therefore, it may be an additional useful tool for identifying individuals at higher risk of prolonged symptoms after COVID-19 infection.},
}
@article {pmid41517410,
year = {2025},
author = {Brogna, B and Nunziata, M and Urciuoli, L and Romano, A and Laporta, A and Brogna, C},
title = {Spontaneous Pneumomediastinum in COVID-19 and Myasthenic-like Symptom Complications in Two Relatives: A Coincidence or Spike Toxicity with Thymic Response in Predisposed Individuals? Two Clinical Cases with a Comprehensive Literature Review.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41517410},
issn = {2077-0383},
abstract = {Pneumomediastinum (PM) in SARS-CoV-2 infections can have a multifaceted presentation. The most frequently described cases of spontaneous PM (SPM) occurred during the first waves of the SARS-CoV-2 pandemic due to alveolar fragility related to severe cases of interstitial pneumonia and vascular injury that predisposed to alveolar destruction and to the Macklin effect in PM development. Cases of SPM were also reported secondary to non-invasive mechanical ventilation (NIV) and to the increasing use of higher doses of corticosteroid therapy. However, true SPM in COVID-19 patients without any identifiable risk factors and presenting as a "Hamman syndrome" (HS) has also been observed, although it represents a very rare clinical entity. Both lung dysbiosis and spike protein toxicity could be implicated in SPM, including cases occurring after COVID-19 vaccination. Furthermore, a variety of clinical entities have been reported that are similar both in COVID-19 infection and after the related COVID-19 vaccination. We present two clinical cases (a 14-year-old boy and his mother), one presenting with SPM and both showing thymic hyperplasia, myasthenic-like symptoms, and long COVID features as a post-vaccination syndrome (PACVS). This report highlights how genetic and familial predisposition could play a role in the thymic response both in COVID-19 infection and after vaccination, involving the toxicity of the spike protein as a common denominator.},
}
@article {pmid41516301,
year = {2025},
author = {Stojanovic, M and Djuric, M and Nenadic, I and Bojic, S and Andrijevic, A and Popovic, A and Pesic, S},
title = {Vascular Complications of Long COVID-From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
pmid = {41516301},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/pathology ; *Thrombosis/etiology/pathology ; *Endothelium, Vascular/physiopathology/pathology ; SARS-CoV-2 ; },
abstract = {Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated not only with respiratory illness but also with profound vascular and coagulation disturbances. Long COVID (LC) is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and palpitations. Mechanistically, SARS-CoV-2 induces direct endothelial injury, promotes a pro-inflammatory cytokine milieu, and activates platelets, leading to immunothrombosis and impaired fibrinolysis. Consequently, patients exhibit microthrombosis, elevated plasma D-dimer, fibrinogen dysregulation, and persistent hypercoagulability. Clinically, this translates into an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, as well as arterial thrombotic events such as myocardial infarction and stroke, which may persist months after acute infection. Understanding the interplay between endothelial injury, inflammation, and coagulation is crucial for risk stratification and the development of preventive and therapeutic strategies. We conducted a systematic narrative review of the literature, including human clinical and mechanistic studies identified through PubMed, Scopus and Web of Science up to 30 September 2025. This review synthesizes current evidence on vascular complications in LC, highlighting endothelial dysfunction as a central pathophysiological nexus linking the acute phase of SARS-CoV-2 infection with chronic LC manifestations.},
}
@article {pmid41516190,
year = {2025},
author = {Mcmillan, P and Turner, AJ and Uhal, BD},
title = {The Central Role of Macrophages in Long COVID Pathophysiology.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
pmid = {41516190},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/physiopathology/pathology/virology ; *Macrophages/immunology/metabolism ; SARS-CoV-2/immunology ; Macrophage Activation/immunology ; Immunity, Innate ; Epigenesis, Genetic ; Spike Glycoprotein, Coronavirus/metabolism/immunology ; Animals ; },
abstract = {This review article attempts to provide a unifying hypothesis to explain the myriad of symptoms and predispositions underlying the development of PASC (Postacute Sequelae of COVID), often referred to as Long COVID. The hypothesis described here proposes that Long COVID is best understood as a disorder of persistent immune dysregulation, with chronic macrophage activation representing the fundamental underlying pathophysiology. Unlike transient post-viral syndromes, Long COVID involves a sustained innate immune response, particularly within monocyte-derived macrophages, driven by persistent spike protein (peripherally in MAIT cells and centrally in Microglial cells), epigenetic imprinting, and gut-related viral reservoirs. These macrophages are not merely activated temporarily but also become epigenetically "trained" into a prolonged inflammatory state, as demonstrated by enduring histone acetylation markers such as H3K27acDNA Reprogramming. It is proposed that recognizing macrophage activation as the central axis of Long COVID pathology offers a framework for personalized risk assessment, targeted intervention, and therapeutic recalibration.},
}
@article {pmid41515532,
year = {2025},
author = {Pahuja, S and Hadidchi, R and Tonge, J and Henry, S and Duong, TQ},
title = {Long-Term Cardiovascular and Mortality Risk in Patients with Pre-Existing Arrhythmia Post-SARS-CoV-2 Infection.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {1},
pages = {},
pmid = {41515532},
issn = {2075-4418},
abstract = {Background/Objectives: Individuals with arrhythmia who survived COVID-19 could be susceptible to long-term cardiovascular complications and clinical outcomes. Methods: We performed a retrospective cohort study of adults with a history of arrhythmia in the Montefiore Health System (1 January 2016-17 August 2024). COVID-19 status was determined by a positive or negative polymerase-chain-reaction test. Outcomes included all-cause mortality, first-time myocardial infarction (MI), heart failure (HF), ischemic or hemorrhagic stroke, and major adverse cardiovascular events (MACE: defined as MI, HF, stroke, or death) > 30 days post-index date. Cox proportional hazards and Fine-Gray competing risk models, adjusted for demographic, clinical, socioeconomic, and COVID-19 vaccination variables, were employed. The association of outcomes with blood biomarkers taken at time of infection were also assessed in hospitalized COVID-19 patients. Results: Among the 6830 arrhythmia patients, 985 were hospitalized for COVID-19, 1591 were not hospitalized for COVID-19, and 4254 did not have COVID-19. Patients hospitalized for COVID-19 had a higher risk of all-cause mortality (adjusted hazard ratio = 2.90, 95% confidence-interval [2.08, 4.04]), first-time MI, HF, and MACE compared to controls without COVID-19. No increased risk was observed among non-hospitalized COVID-19-positive patients compared to controls, except for all-cause mortality. Older age, male sex, Medicaid, and significant comorbidities were associated with the risk of MACE. Elevated levels of creatinine, lactate dehydrogenase, D-dimer, neutrophil-to-lymphocyte ratio, low hemoglobin, and low left ventricular ejection fraction during infection were associated with higher future MACE risk. Conclusions. In individuals with arrhythmia, severe COVID-19 is associated with increased long-term risks of mortality and new-onset cardiovascular complications, while mild infection with mortality risk. These findings highlight the need for long-term cardiovascular monitoring in this population.},
}
@article {pmid41514842,
year = {2025},
author = {González-Hermosillo González, JA and Lerma, C and Celestino Montelongo, DA and Alba Lorenzo, MDC and Salas Santos, E and Gun Cuninghame Ballesteros, A and Jorge-Galarza, E and Martínez-Alvarado, MDR},
title = {Long COVID Patients with Orthostatic Intolerance Have Reduced Heart Rate Variability and Preserved Physiological Response to Active Standing.},
journal = {Biology},
volume = {15},
number = {1},
pages = {},
pmid = {41514842},
issn = {2079-7737},
support = {DGPIS-FPIS 2024/ INCAR-7116//Direcci&#xf3;n General de Pol&#xed;ticas de Investigaci&#xf3;n en Salud/ ; },
abstract = {The aim of this study was to assess the heart rate variability (HRV) at rest and during active orthostatic challenge in long COVID patients with orthostatic intolerance symptoms (dizziness, pre-syncope, and syncope). We performed a cross-sectional, observational, comparative study of 60 subjects of both sexes, aged 18 to 60 years (31 met the criteria of long COVID, 15 were infected individuals without symptoms, and 14 who had neither infection nor symptoms formed the age-matched control group). HRV was obtained from continuous electrocardiograms in a supine position and active standing with spontaneous breathing. The time from SARS-CoV-2 infection to testing in the COVID-19 group was 573 ± 289 days. The resting (supine position) values of SDNN, RMSSD, SD1, and SD2 were lower in long COVID patients than in control participants, while all other HRV indexes were similar between groups. In response to active standing, both groups had similar changes in all HRV indices. In conclusion, an active orthostatic test was not able to exhibit an autonomic dysregulation in these patients with long COVID, suggesting that cardiac autonomic modulation may have recovered due to the long time that elapsed after SARS-CoV-2 infection.},
}
@article {pmid41513611,
year = {2026},
author = {Nunes, M and Kell, L and Slaghekke, A and Wüst, RC and Fielding, BC and Kell, DB and Pretorius, E},
title = {Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.},
journal = {Cell death &amp; disease},
volume = {17},
number = {1},
pages = {16},
pmid = {41513611},
issn = {2041-4889},
support = {NNF20CC0035580//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; },
mesh = {Humans ; *COVID-19/immunology/virology/pathology/complications ; SARS-CoV-2 ; *Cellular Senescence ; *Fatigue Syndrome, Chronic/immunology/virology/pathology ; *Endothelial Cells/pathology/virology/immunology ; *Immune System/pathology ; *Endothelium, Vascular/pathology/virology ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are two post-viral diseases, which share many common symptoms and pathophysiological alterations. Yet a mechanistic explanation of disease induction and maintenance is lacking. This hinders the discovery and implementation of biomarkers and treatment options, and ultimately the establishment of effective clinical resolution. Here, we propose that acute viral infection results in (in)direct endothelial dysfunction and senescence, which at the blood-brain barrier, cerebral arteries, gastrointestinal tract, and skeletal muscle can explain symptoms. The endothelial senescence-associated secretory phenotype (SASP) is proinflammatory, pro-oxidative, procoagulant, primed for vasoconstriction, and characterized by impaired regulation of tissue repair, but also leads to dysregulated inflammatory processes. Immune abnormalities in ME/CFS and long COVID can account for the persistence of endothelial senescence long past the acute infection by preventing their clearance, thereby providing a mechanism for the chronic nature of ME/CFS and long COVID. The systemic and tissue-specific effects of endothelial senescence can thus explain the multisystem involvement in and subtypes of ME/CFS and long COVID, including dysregulated blood flow and perfusion deficits. This can occur in all tissues, but especially the brain as evidenced by findings of reduced cerebral blood flow and impaired perfusion of various brain regions, post-exertional malaise (PEM), gastrointestinal disturbances, and fatigue. Paramount to this theory is the affected endothelium, and the bidirectional sustainment of immune abnormalities and endothelial senescence. The recognition of endothelial cell dysfunction and senescence as a core element in the aetiology of both ME/CFS and Long COVID should aid in the establishment of effective biomarkers and treatment regimens.},
}
@article {pmid41512730,
year = {2026},
author = {Patel, A and Cherian, C and Ge, D and Hussain, S and Shu, C and Chen, MH and , },
title = {Neurological sequela of COVID-19 in adults with multiple sclerosis.},
journal = {Multiple sclerosis and related disorders},
volume = {107},
number = {},
pages = {106944},
doi = {10.1016/j.msard.2025.106944},
pmid = {41512730},
issn = {2211-0356},
mesh = {Humans ; *COVID-19/complications/epidemiology/mortality ; Female ; Male ; *Multiple Sclerosis/complications/epidemiology ; Middle Aged ; Adult ; Retrospective Studies ; SARS-CoV-2 ; *Cognitive Dysfunction/epidemiology ; Hospitalization/statistics &amp; numerical data ; Aged ; },
abstract = {BACKGROUND: Possible interactions in neuropsychiatric presentations of multiple sclerosis (MS) and COVID-19 may occur, which has been proposed in previous, albeit limited, literature.<br><br>OBJECTIVES: Examine COVID-19 disease outcomes and changes in neuropsychiatric symptoms among patients with MS.<br><br>METHODS: A retrospective cohort study using electronic medical records from the National COVID Cohort Collaborative (N3C) database was conducted. 26,963 adults with MS diagnosed with COVID-19 were included in the study, and propensity score matched to 80,889 neurologically healthy adults with COVID-19. Group differences in risk for general COVID-19 disease outcomes, 15 acute COVID-19-associated neuropsychiatric complications, and 6 chronic MS-associated neuropsychiatric symptoms were assessed.<br><br>RESULTS: Patients with MS were at a higher risk for mortality; hospitalization; long-COVID diagnosis; more severe COVID-19 disease; 9 of the 15 acute complications, including cognitive impairment (OR: 4.059, p < 0.001), neuralgia (OR: 3.961, p < 0.001), dysautonomia (OR: 2.740, p < 0.008), and paresthesia (OR: 2.522, p < 0.001); and 5 of the 6 chronic symptoms, including cognitive impairment (OR: 2.945, p < 0.001), fatigue (OR: 2.190, p < 0.001), and depression (OR: 1.345, p < 0.001).<br><br>CONCLUSIONS: Patients with MS are at risk for adverse COVID-19 outcomes. This warrants heightened caution in this population when managing COVID-19 infections.},
}
@article {pmid41511567,
year = {2026},
author = {Stavem, K and Garratt, AM},
title = {Validity of EQ-5D-5L breathing and cognition bolt-ons in non-hospitalized patients after COVID-19.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {2},
pages = {31},
pmid = {41511567},
issn = {1573-2649},
mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; *Quality of Life ; Surveys and Questionnaires/standards ; Aged ; SARS-CoV-2 ; Adult ; Cognition ; Reproducibility of Results ; Psychometrics ; Respiratory Function Tests ; },
abstract = {PURPOSE: The EQ-5D has been criticized for lacking dimensions for breathing and cognition. In acute COVID-19 and Long COVID, breathing problems and cognitive complaints are common. This study evaluated the inclusion of EQ-5D-5L (bolt-on) items that assess these dimensions.<br><br>METHODS: In a follow-up of community-based non-hospitalized patients with COVID-19 in 2020 (n&#x2009;=&#x2009;450), we used respiratory and cognitive bolt-on items alongside other questionnaires about 30&#xa0;months later (n&#x2009;=&#x2009;220). We assessed data quality and construct validity for the bolt-ons, including comparison with concurrently used instruments' domain and item scores. Bolt-on scores were correlated with pulmonary function tests and tablet-based cognitive tests about 1&#xa0;year earlier. Finally, we assessed the contribution of the bolt-ons to variability of the EQ VAS.<br><br>RESULTS: Most patients had none or slight problems with breathing and cognition. The breathing problems bolt-on had an 8% lower ceiling effect, but otherwise a similar response distribution to the mMRC. Cognition bolt-on and four DSQ-SF item scores relating to frequency and severity were similar, except 2-13% higher ceiling effects for the former. The breathing bolt-on had a rank correlation of 0.54 with mMRC scores and higher correlations with Dyspnoea-12 scale scores. EQ-5D-5L dimensions explained 54% of variation in EQ VAS scores; the breathing bolt-on contributed a further 2%, but the cognition bolt-on contributed very little.<br><br>CONCLUSION: The results support the validity of the two bolt-ons in follow-up of non-hospitalized patients after COVID-19. Adding items of respiratory and cognitive symptoms may enhance the EQ-5D's appropriateness in respiratory and cognitive research and clinical practice.},
}
@article {pmid41510565,
year = {2026},
author = {Purpura, L and Heisler, T and Palmer, S and Shah, J and Graham, A and Seo, GY and Sturiza, A and Javier, X and Pinto, G and Rosa, A and Bosco, J and Reis, K and Sobieszczyk, ME and Yin, MT},
title = {Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf624},
pmid = {41510565},
issn = {1537-6591},
support = {//National Institute of Allergy and Infectious Diseases/ ; K23 AI171263/NH/NIH HHS/United States ; K24 AI155230/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Postacute sequelae of COVID-19 (PASC), also known as long COVID, and postacute COVID-19 vaccination syndrome (PACVS) present overlapping but distinct clinical challenges. We hypothesize that PASC and PACVS share clinical features but differ in symptom patterns and biomarker profiles. This study aims to identify differences in presentation and distinguish immunologic biomarkers relevant to general clinical practice.<br><br>METHODS: This cross-sectional study analyzed 181 patients from a PASC clinic at Columbia University Irving Medical Center. Patients were divided into PASC with myalgic encephalomyelitis/chronic fatigue syndrome (MECFS), PASC without MECFS (LC), and PACVS groups. Prevalence and severity of self-reported symptoms, as well as immunologic abnormalities, were compared across groups.<br><br>RESULTS: Fatigue was the most common symptom (Total: 88.95%; MECFS: 100.00%; PACVS: 92.86%; LC: 78.05%). The MECFS group generally reported more symptoms across all organ systems. The PACVS group reported higher rates of atypical chief complaints such as peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) compared to the other groups (P = <.01). Functional impairment was comparable between the MECFS and PACVS groups and less severe in the LC group. All groups had high rates of autoantibody positivity and cytokine elevation. The PACVS group showed significantly higher rates of anticardiolipin IgM (PACVS 42.9%, LC 11.6%; P = .02) and anti-U1-RNP (PACVS 21.4%, LC 2.3%; P = .04) positivity compared to the LC group.<br><br>CONCLUSIONS: PASC and PACVS share symptom overlap but exhibit distinct biomarker patterns, particularly elevated autoantibody levels in PACVS. These findings suggest autoimmune involvement, warranting further investigation for targeted therapies.},
}
@article {pmid41509610,
year = {2026},
author = {Wang, B and Luo, X and Wu, M and Wang, Z and Zhang, J and Wang, Z and Shi, Q and Liu, J and Cao, W and Gu, X and Chen, Y and Cao, B and Estill, J},
title = {Identifying subtypes of Long COVID: a systematic review.},
journal = {EClinicalMedicine},
volume = {91},
number = {},
pages = {103705},
pmid = {41509610},
issn = {2589-5370},
abstract = {BACKGROUND: Long COVID, a persistent condition following SARS-CoV-2 infection, exhibits diverse symptoms across multiple organ systems. This study aims to summarize the existing clustering and classification approaches to support the management of Long COVID.<br><br>METHODS: Following PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, and Google Scholar from their inception to January 21, 2025, and updated the search on October 1, 2025, to identify studies that presented a way to categorize Long COVID patients or symptoms. Data extraction and quality assessment were conducted for eligible studies. We presented symptom co-occurrence networks, and performed meta-analysis to estimate the percentage of different organ system-based symptom clusters. In addition, we conducted an exploratory analysis of the determinants of different symptom clusters. The protocol was registered in OSF (https://doi.org/10.17605/OSF.IO/J483F).<br><br>FINDINGS: Forty-seven cohort studies and 17 cross-sectional studies categorizing Long COVID subtypes or symptoms were included, encompassing 2.43 million participants across 20 countries. The methodological quality of the cohort studies was on average high (mean Newcastle-Ottawa scale score: 7.5/9), and of the 17 cross-sectional studies moderate (mean Joanna Briggs Institute tool score: 0.61/1.00). Patients or symptoms were categorized either according to the co-occurrence of symptoms (n = 30 studies, 46.9%); by the affected organ system (n = 16, 25.0%); by severity stratification (n = 9, 14.1%); by clinical indicators (n = 3, 4.7%); or by using other ways of classification (n = 6, 9.4%). Among the 30 studies defining patient clusters by the co-occurrence of symptoms, fatigue was the most frequently used descriptor for a cluster, either alone or together with other symptoms (n = 15 studies). Pairwise co-occurrence analysis revealed some commonly used symptom dyads, including olfactory-gustatory dysfunction (n = 10 times), anxiety-depression (n = 10) and joint pain/swelling-muscle pain (n = 9). Fatigue was a recurrent core symptom, frequently co-occurring with joint pain/swelling (n = 9 times) or muscle pain (n = 7), cognitive symptoms (n = 7), and dyspnea (n = 7). Meta-analysis of the organ system-based subtypes showed that respiratory symptom cluster had the highest pooled percentage (47% [95% CI: 29%-65%]), followed by neurological (31% [95% CI: 3%-60%]) and gastrointestinal clusters (28% [95% CI: 0%-57%]). These percentages represent the proportion of Long COVID patients with each symptom cluster within the 16 included organ system-based subtyping studies, not population-level prevalence of Long COVID. Exploratory analysis indicated that symptom subtypes were influenced by factors such as sex, age, virus variant, and comorbidities.<br><br>INTERPRETATION: This review identified four major approaches for categorizing Long COVID patients and their symptoms. Symptom co-occurrence and organ system were the most commonly used subtypes used in categorization. Fatigue and olfactory-gustatory dysfunction emerged as recurrent core symptoms across multiple subtypes of Long COVID.<br><br>FUNDING: This work was supported by the K. C. Wong Education Foundation, Hong Kong, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2024-I2M-ZD-011), the Beijing Nova Program (20240484523), the Elite Medical Professionals Project of China-Japan Friendship Hospital (NO. ZRJY2024-GG03), and the National High Level Hospital Clinical Research Funding.},
}
@article {pmid41505721,
year = {2026},
author = {Bova, ML and Palmore, TN and Diao, G and Russell, JA and Magnus, M},
title = {Strategies for forecasting long COVID in the active component U.S. military.},
journal = {MSMR},
volume = {32},
number = {10},
pages = {29-38},
pmid = {41505721},
issn = {2152-8217},
mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; *Military Personnel/statistics &amp; numerical data ; United States/epidemiology ; Forecasting/methods ; SARS-CoV-2 ; Machine Learning ; Incidence ; Male ; Female ; Models, Statistical ; Adult ; },
abstract = {Long COVID, or post-acute coronavirus disease syndrome, represents a potentially serious threat to military readiness. Forecasts of future long COVID diagnoses could help prepare senior leaders for disruptions. Few studies predicting the incidence of long COVID have been published to date, however. Using existing COVID-19 and long COVID diagnoses, as well as demographic and outpatient encounter data, 1- to 6-month ahead and full 6-month forecasts were generated using time series and machine learning models trained on various covariate data. Forecasting models generated accurate predictions of long COVID diagnoses up to 6 months ahead of the forecasted date. Several model and covariate combinations were within 5% of the observed number of diagnoses over the full 6-month testing period, while monthly forecasts of long COVID diagnoses had median absolute percentage errors ranging from 3% to 10% for the best performing model combinations. Simple forecasting models and distribution-based forecasts that utilize existing clinical databases can provide accurate predictions of incident long COVID up to 6 months in advance and can be used to prepare for the burden of new long COVID diagnoses. Accurate predictions of long COVID cases over a 6-month period were achieved by utilizing existing COVID-19 case and outpatient encounter data from January 1, 2020, through December 31, 2022. Long COVID symptoms can cause disruptions to military readiness and prevent a healthy force, especially after surges in COVID-19 cases. The ability to use existing data sources to accurately predict future cases of long COVID allows senior leaders to anticipate and prepare for potential changes in the availability of service members.},
}
@article {pmid41505348,
year = {2026},
author = {Lin, DY and Mischell, MA and Zhang, X and Mollan, KR and Zhang, N and Nanyakkara, D and Keys, JR and Straub, B and Wohl, D and Fischer, W},
title = {Incidence and Severity of Postacute Sequelae of SARS-CoV-2 Infection in the Omicron Era: A Prospective Cohort Study.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag026},
pmid = {41505348},
issn = {1537-6613},
abstract = {In a prospective cohort study of 2,960 non-hospitalized adults with acute SARS-CoV-2 infection, older age, female sex, rural residence, high BMI, greater acute infection severity, chronic lung disease, and poorer general health at baseline were associated with higher risk and severity of postacute sequelae. Recent vaccination was associated with lower postacute sequelae risk and severity, while antiviral therapy was not.},
}
@article {pmid41503738,
year = {2026},
author = {Yar, S and Rafieossadat, R and Chhetri, PK},
title = {Bridging Electrophysiology and Digital Health: Microneurography Findings in Long COVID Herald a New Era of AI-Powered Peripheral Nerve Monitoring.},
journal = {Annals of neurology},
volume = {99},
number = {2},
pages = {542-543},
doi = {10.1002/ana.78127},
pmid = {41503738},
issn = {1531-8249},
}
@article {pmid41503716,
year = {2026},
author = {Gamillscheg-Müllner, P and Łaszewska, A and Diexer, S and Hoffmann, K and Simon, J and Mayer, S},
title = {Theoretically Universal, Practically Unequal: Socio-Economic Inequalities in Healthcare Access for Long Covid-19 Patients in Austria.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {1},
pages = {e70553},
pmid = {41503716},
issn = {1369-7625},
support = {SO68900010//Medical University of Vienna and the University of Vienna/ ; },
mesh = {Humans ; *COVID-19/therapy/epidemiology ; Female ; Male ; Austria/epidemiology ; Cross-Sectional Studies ; *Health Services Accessibility/statistics &amp; numerical data ; Middle Aged ; Adult ; Retrospective Studies ; Socioeconomic Factors ; *Healthcare Disparities/statistics &amp; numerical data ; Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long Covid-19 (LC) patients have substantial treatment and care needs, yet research has shown that the majority of them experience healthcare access barriers. While qualitative studies indicate socio-economic and demographic access inequalities among LC patients, quantitative evidence remains limited. This study aims to assess socio-economic inequalities in healthcare access among LC patients in Austria, focusing on self-perceived barriers, facilitators and unmet healthcare needs.<br><br>METHODS: Retrospective cross-sectional data were collected from adult LC patients through online and paper-based surveys (10-12/2024), following a prior qualitative study. The survey assessed 47 barriers and 10 facilitators based on Levesque's 'access to care' framework, along with unmet healthcare needs overall and related to general practitioner (GP), specialist and hospital care. Overall barrier and facilitator scores were calculated. Inequalities related to gender, age, urbanicity, health-related background through training/employment, complementary private health insurance, and economic situation were examined in linear, logistic and ordered logistic regressions, controlling for clinical and demographic variables.<br><br>RESULTS: Overall, 433 LC patients completed the survey. Participants living in urban areas, with complementary private health insurance, or in a good economic situation reported fewer barriers, reflected in statistically significantly lower overall barrier scores. Income-related inequalities emerged particularly in relation to barriers in GP care, including not being taken seriously, attribution of symptoms to mental health conditions, burdensome costs, short consultation times, and limited availability of telemedicine or home visits. Facilitator scores, in contrast, did not differ by socio-economic factors. Living in a rural area was associated with a higher probability of unmet healthcare needs related to GP and specialist care. A poor economic situation was associated with a higher probability of reporting unmet needs related to specialist and hospital care. No evidence of gender-based inequalities was found.<br><br>CONCLUSIONS: Our findings reveal enhanced inequalities in LC healthcare access in an otherwise universal healthcare system. Contrary to prior research, we find income-related inequalities in GP access. Future policy efforts in Austria should consider that central case management through GP care may not be the most optimal set-up, especially without improved information, training, support and specialist referral opportunities.<br><br>The design of the survey and the hypotheses on healthcare access barriers and facilitators were directly informed by qualitative interviews from previous work with long Covid-19 (LC) patients, who shared their lived experiences with diagnosis, treatment and navigating the healthcare system. Additionally, LC patients piloted the survey before its launch and provided feedback. Representatives of patient LC groups and individual patients contributed to participant recruitment by sharing study materials within their networks.},
}
@article {pmid41503710,
year = {2026},
author = {Ribeiro, A and Hadavi, S and Gall, N and Hadden, RDM and Serra, J},
title = {Reply to: "Bridging Electrophysiology and Digital Health: Microneurography Findings in Long COVID Herald a New Era of AI-Powered Peripheral Nerve Monitoring".},
journal = {Annals of neurology},
volume = {99},
number = {2},
pages = {543},
doi = {10.1002/ana.78141},
pmid = {41503710},
issn = {1531-8249},
}
@article {pmid41502583,
year = {2026},
author = {Rourke, L and Damant, R},
title = {A short version of the post-COVID-19 condition stigma questionnaire.},
journal = {Public health in practice (Oxford, England)},
volume = {11},
number = {},
pages = {100696},
pmid = {41502583},
issn = {2666-5352},
abstract = {OBJECTIVES: The purpose of this study was to develop a short version of the 40-item Post-COVID-19 Condition Stigma Questionnaire (PCCSQ) while preserving its factor structure, reliability, and validity. The PCCSQ is a sound tool for assessing the discrimination experienced by people with a diagnosis of long covid, but a shorter version would be less demanding of respondents experiencing fatigue and brain fog and easier for clinicians and researchers to administer.<br><br>STUDY DESIGN: This was an observational study.<br><br>METHODS: From the original 40-items measuring the 6-factor construct long covid stigma, we assembled 12 items that represented the factors and discriminated among participants with high and low levels of stigma. We administered the shorter questionnaire to 99 long covid patients and assessed several of its measurement properties.<br><br>RESULTS: The 12-item instrument maintains the 6-factor structure of long covid stigma, has a mean discrimination index of 0.40 (sd&#xa0;=&#xa0;0.08; range 0.22-0.48), an internal consistency of &#x3b1;&#xa0;=&#xa0;0.89, a split-half reliability of 0.86, and it correlates predictably with theoretically-related variables.<br><br>CONCLUSIONS: The PCCSQ-12 is a feasible, reliable and valid means of assessing patients' experience of long covid stigma.},
}
@article {pmid41499397,
year = {2026},
author = {Verma, AK and Tan, L and Schuster, N and Moye, SL and Lin, LC and Lowery, S and Duraisami, E and Lloréns, JEA and Qiu, Q and Hefti, M and Meyerholz, DK and Coleman, MC and Yu, CR and Albers, MW and Perlman, S},
title = {Combination antiviral and anti-inflammatory therapy mitigates persistent neurological deficits in mice post SARS-CoV-2 infection.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {2},
pages = {e2530209123},
pmid = {41499397},
issn = {1091-6490},
support = {RF1 AG078297//HHS | NIH | National Institute on Aging (NIA)/ ; R01 NS036592/NS/NINDS NIH HHS/United States ; R01 NS36592//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 AI129269/AI/NIAID NIH HHS/United States ; P01 AI060699/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Antiviral Agents/therapeutic use/pharmacology ; *COVID-19/complications/virology/pathology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Humans ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Male ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Mice, Inbred C57BL ; *Nervous System Diseases/drug therapy/etiology/virology ; Brain/pathology ; },
abstract = {Post-acute sequelae of COVID-19 (PASC) encompasses persistent neurological disease, including olfactory and cognitive dysfunction. The basis for this dysfunction is poorly understood. Here, we report neurological dysfunction for at least 120 d postinfection in mice infected with a virulent nonneurotropic mouse-adapted SARS-CoV-2. Long after recovery from nasal infection, we observed diminished tyrosine hydroxylase expression in olfactory bulb glomeruli and in substantia nigra. Similar changes were observed in brains of COVID-19 deceased patients. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased proinflammatory cytokines, and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, similar to human neurodegenerative diseases. Treatment with antivirals (nirmatrelvir and molnupiravir) at the time of infection minimally prevented neurological abnormalities, consistent with patient data. In contrast, antivirals plus corticosteroids resulted in nearly complete recovery of neurological function. Remarkably, initiation of combined therapy even three days after infection improved outcomes. Together these results demonstrate that neurological dysfunction in SARS-CoV-2 infected mice resembles human neurodegenerative disease and indicate that minimizing inflammation early after SARS-CoV-2 infection may be critical for decreasing neurological PASC. The requirement for decreasing inflammation soon after infection may also explain why antiviral therapy has had inconsistent effects in patients.},
}
@article {pmid41498966,
year = {2026},
author = {Cao, Y and Lizano, P and Garza, AP and Dunay, IR and Zhou, X and Reuken, PA and Stallmach, A and Walter, M and Li, M and Besteher, B},
title = {Choroid plexus alterations in long COVID and their associations with IL-6.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41498966},
issn = {1433-8491},
support = {FKZ: 01EE2103//the DZPG (German Center for Mental Health)/ ; none//Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan/ ; K23MH122701//National Institute of Health grants/ ; },
abstract = {SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently leading to demyelination, white matter (WM) damage in long COVID, and clinical worsening. The role of the ChP in long COVID and its relationships to WM integrity, IL-6, clinical symptoms, and ACEIs/ARBs medications remains unclear. Fifty-two long COVID individuals, 21 COVID-19 survivors, and 26 healthy controls (HCs) completed Montgomery-Asberg Depression Rating Scale (MADRS), Montreal Cognitive Assessment (MoCA) and interleukin (IL) -6 assessments. Manually segmented ChP volume and global free water corrected WM integrity was compared among groups, and consideration of ACE inhibition on the ChP was examined. Partial correlations explored relationships among ChP volume, IL-6, fractional anisotropy tissue (FAt), and symptoms. ChP changes were also assessed at baseline and after one year. Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups. Larger ChP volume was significantly correlated to higher IL-6 levels (r = 0.478, p = 0.005) in long COVID. No ChP volume differences were found over time in the long COVID group or HCs that transitioned to COVID-19 survivors. COVID-19 survivors had larger ChP volume at follow-up compared to baseline (p = 0.04). The smaller ChP in long COVID seems to involve persistent but low-grade blood-CSF barrier dysfunction and epithelial stress. IL-6 levels may affect ChP permeability and suggest ongoing neuroinflammation in the long COVID group.},
}
@article {pmid41497070,
year = {2026},
author = {Obeagu, EI},
title = {Immunomodulatory strategies for managing cytokine storms in chronic COVID: mechanisms, therapeutic targets, and clinical advances.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {1},
pages = {653-659},
pmid = {41497070},
issn = {2049-0801},
abstract = {Chronic COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, is increasingly linked to sustained immune dysregulation, particularly cytokine storms that drive chronic inflammation and multi-organ complications. Understanding the mechanisms underlying cytokine dysregulation in chronic COVID is essential for developing effective therapeutic strategies aimed at restoring immune balance and mitigating long-term morbidity. This review critically examines current immunomodulatory strategies for managing cytokine storms in chronic COVID, including corticosteroids, cytokine-specific biologics, Janus kinase inhibitors, and emerging cell-based therapies. Additionally, the role of biomarker-guided precision medicine in personalizing treatment to optimize efficacy and safety is discussed. Challenges such as patient heterogeneity, timing and duration of therapy, and potential adverse effects are also addressed. Future research directions emphasize the need for robust clinical trials, novel therapeutic development, and integrated multidisciplinary care to improve patient outcomes. By tailoring immunomodulatory approaches based on individual immune profiles, it is possible to enhance the management of cytokine-driven inflammation in chronic COVID and advance the field toward more effective, personalized treatments.},
}
@article {pmid41496808,
year = {2025},
author = {Woods, JA and Hutchinson, NT and Powers, SK and Gomez-Cabrera, MC and Radak, Z and Leeuwenburgh, C and Cacciatore, S and Marzetti, E and Zhang, T and Garza, R and Sidebottom, C and Anderson, E and Durstine, JL and Sun, J and Ji, LL},
title = {Physical activity during COVID-19 pandemic: A 5-year retrospect.},
journal = {Sports medicine and health science},
volume = {7},
number = {6},
pages = {405-418},
pmid = {41496808},
issn = {2666-3376},
abstract = {The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019 (COVID-19) pandemic on human health and the role of physical activity (PA) during the 5-year pandemic. We aim to cover the immune system, the cardiopulmonary system, the musculoskeletal system, and the central nervous system (brain function), particularly among older adults, college students, and individuals with post-acute sequelae of COVID-19 (Long-COVID). The COVID-19 pandemic has given us many lessons, learned from the death of six million lives and tremendous disturbance to human life. First, we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection. Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines. The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research. Available evidence suggests that mitochondrial dysfunction, reduced microcirculation and latent immune activation play a major role, eventually impairing cardiovascular tolerance and peripheral bioenergetics. Second, the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor. Conversely, physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems. If not intervened, this interaction can lead to Long-COVID, a dangerous futile circle to cause systemic failure. Finally, the COVID-19 pandemic has exerted differential impacts on different populations. Thus, the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific, flexible and tailored to fit different patient populations.},
}
@article {pmid41496063,
year = {2026},
author = {Tang, L and Jie, Z and Zheng, D and Hua, Q and Cai, S and Li, C and Cai, Y and Jin, L and Yang, R and Zhang, Z},
title = {Effect of Fuzheng series of formulas on the psychological state, dyspnea, and quality of life in convalescent COVID-19 patients: A retrospective observational study.},
journal = {Medicine},
volume = {105},
number = {1},
pages = {e46375},
pmid = {41496063},
issn = {1536-5964},
mesh = {Humans ; *Quality of Life ; Retrospective Studies ; Male ; Female ; *Dyspnea/drug therapy/etiology/psychology ; Middle Aged ; *COVID-19/psychology/complications ; *Drugs, Chinese Herbal/therapeutic use ; Adult ; *COVID-19 Drug Treatment ; Aged ; SARS-CoV-2 ; },
abstract = {Post-infectious symptoms of COVID-19-such as persistent dyspnea, psychological disturbances, and reduced quality of life-continue to pose significant health challenges for convalescent patients. Traditional Chinese Medicine (TCM) has been widely used as a complementary therapeutic approach to alleviate post-COVID sequelae. This retrospective study evaluated the clinical effects of 2 TCM prescriptions, Fuzheng Yifei Formula (FZYF) and Fuzheng Anshen Formula (FZAS), on the psychological state, dyspnea, and quality of life among patients recovering from COVID-19. Medical records of 114 COVID-19 convalescent patients treated at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine were retrospectively reviewed. Based on the treatment regimen, patients were categorized into 2 groups: FZYF (n = 77) and FZAS (n = 37). Clinical data were collected at baseline, 7 days, 14 days, and during follow-up. Changes in psychological status, dyspnea severity, and quality-of-life scores were analyzed using validated assessment tools, including the General Health Questionnaire (GHQ-12), the Modified Borg Scale, and the 36-Item Short Form Survey (SF-36) Health Survey. Both FZYF and FZAS were associated with significant improvements in psychological well-being, with mean GHQ-12 scores decreasing from 14.5 at baseline to 9 at follow-up (P < .05). Dyspnea symptoms improved across both groups, with an average reduction of 3.5 points on the Modified Borg Scale. The SF-36 results indicated notable enhancements in both physical and mental health domains, showing mean improvements of 22% and 23%, respectively. No statistically significant difference was found between the 2 formulas, although FZYF showed slightly superior benefits in respiratory symptom relief. The retrospective analysis suggests that the FZYF may help alleviate long-term respiratory and psychological symptoms among COVID-19 convalescents, thereby potentially improving their overall quality of life. The FZAS, while showing comparable trends of benefit, appeared to exert relatively greater influence on mental and emotional well-being. However, these findings should be interpreted with caution given the non-randomized design and limited sample size, and further validation through large-scale controlled studies is warranted.},
}
@article {pmid41494637,
year = {2026},
author = {Wu, Q and Zhao, Y and Fang, X and Chen, T and Zhang, C and Liu, Z and Wang, C},
title = {Longitudinal Changes in Long COVID Symptoms by Sex and Age Among Geriatric Residents of Residential Care Facilities: A Multicenter Cohort Study in Hefei, China.},
journal = {Journal of the American Medical Directors Association},
volume = {27},
number = {3},
pages = {106071},
doi = {10.1016/j.jamda.2025.106071},
pmid = {41494637},
issn = {1538-9375},
abstract = {OBJECTIVES: This study aimed to investigate the symptomatic evolution of long COVID and to identify factors influencing its progression in a predominantly older population.<br><br>DESIGN: This was a prospective cohort study with long-term follow-up, conducting 3 assessment waves between January 8, 2023, and August 15, 2024.<br><br>SETTING AND PARTICIPANTS: The study included 228 of an initial cluster sample of 266 residents from 5 long-term care facilities in Hefei, China, all with prior SARS-CoV-2 infection, who completed all follow-ups.<br><br>METHODS: Data were collected via study-specific demographic questionnaires and a long COVID symptom scale. Descriptive statistics, Cochran's Q tests, t tests, partial correlations controlling for age, and generalized estimating equations were used to analyze symptom distribution, comparisons, longitudinal relationships, and influencing factors.<br><br>RESULTS: At T1, low mood (81.1%) and sleep disturbances (81.1%) were the most common symptoms. At T2, fatigue (54.8%) and pain in other body parts (59.2%) became the main symptoms. Dizziness (44.7%) was the most frequent symptom at T3. Independent samples t tests revealed that women had consistently higher total symptom scores than men (P < .05). Compared with the younger group (<76 years), the older group (&#x2265;76 years) had higher scores at T2 across multiple symptoms and in the overall score. Partial correlation analysis showed the correlation was strongest between T1 and T2 (r = 0.224, P = .001). The generalized estimating equations model indicated that men had a lower risk of symptoms in most organ systems (OR = 0.257-0.912).<br><br>CONCLUSIONS AND IMPLICATIONS: Long COVID symptoms in predominantly older individuals showed progressive improvement. Women had more severe symptoms and advanced age slowed the recovery process. However, long-term recovery depended on the individual. This study advocates for implementing personalized, stage-specific care models over standardized protocols in residential care facilities, emphasizing the need for targeted monitoring of high-risk subgroups such as women and older residents.},
}
@article {pmid41494551,
year = {2026},
author = {Rubin, LH and Azola, A and Yoo-Jeong, M and Dastgheyb, RM and Easter, R and Ehrenspeck, A and Coughlin, JM and Vannorsdall, TD and Veenhuis, RT and Wilson, TE},
title = {Cognitive sequala of loneliness in long COVID: Differential associations by loneliness subtypes.},
journal = {Journal of affective disorders},
volume = {399},
number = {},
pages = {121101},
pmid = {41494551},
issn = {1573-2517},
support = {P30 MH075673/MH/NIMH NIH HHS/United States ; RF1 MH133411/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; *Loneliness/psychology ; Male ; Female ; *COVID-19/psychology/complications ; Aged ; Middle Aged ; *Cognitive Dysfunction/psychology/etiology ; Neuropsychological Tests ; Cognition ; Social Isolation/psychology ; },
abstract = {BACKGROUND/OBJECTIVE: Loneliness is a risk factor for cognitive decline in aging and other clinical populations, but its role in long COVID (LC) remains poorly understood. Individuals with LC may be particularly vulnerable to loneliness due to debilitating, persistent symptoms and reduced functioning. We examined associations between overall loneliness and cognition in LC versus recovered controls, and whether loneliness subtypes (social, emotional) differentially relate to cognitive function.<br><br>METHODS: Individuals meeting 2024 National Academy of Science, Engineering and Medicine criteria (NASEM) for LC and reporting at least one neuropsychiatric symptom (n&#xa0;=&#xa0;120), along with recovered controls (n&#xa0;=&#xa0;51), completed the 6-item De Jong Gierveld Loneliness Scale and a cognitive test battery. Correlation analyses, corrected for false discovery rate, identified bivariate loneliness-cognition associations. Significant correlations were followed by age-adjusted regressions using residualized loneliness scores, which excluded variance shared with depression and social isolation.<br><br>RESULTS: LC participants reported higher overall, emotional, and social loneliness than controls. In bivariate analyses, greater overall and emotional loneliness were associated with more subjective cognitive complaints and poorer verbal fluency in the full sample and LC group, and with cognitive complaints and poorer verbal memory in controls. In adjusted models, residual overall and emotional loneliness remained significantly associated with fluency in LC and the full sample, and with memory in controls. Associations with cognitive complaints did not persist. Social loneliness showed weaker and inconsistent associations.<br><br>CONCLUSION: Overall and emotional loneliness are independently linked to objective cognitive difficulties. Findings highlight emotional loneliness as a potential target for cognitive intervention in LC and recovered individuals.},
}
@article {pmid41494535,
year = {2026},
author = {Wang, M and Chen, Y and Guo, M and Xie, P and Zhao, X and Chen, S and Deng, Y and Hu, R and Wan, Q and Zhou, J and Zhang, Z and Lan, K and Chen, H and Liu, Y},
title = {Impaired VLCFA-peroxisome-mediated intestinal epithelial repair causes gastrointestinal sequelae of long COVID.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2025.12.003},
pmid = {41494535},
issn = {1878-1551},
abstract = {Long COVID has emerged as a significant public health challenge with no effective treatments currently available, yet the pathophysiological mechanisms underlying its persistent gastrointestinal (GI) symptoms remain poorly understood. Here, integrating clinical data with transgenic animal models, we discover a critical role for impaired intestinal epithelial repair in the local intestinal etiology of long COVID. Mechanistically, we show that intestinal SARS-CoV-2 reservoirs disrupt very-long-chain fatty acid (VLCFA) metabolism, suppressing activation of peroxisome proliferator-activated receptor (PPAR) signaling and reducing peroxisome abundance. This disruption impairs intestinal stem cell differentiation and epithelial regeneration, resulting in prolonged GI symptoms including diarrhea, inflammation, and microbiota dysbiosis. Importantly, the FDA-approved sodium phenylbutyrate (NaPB) and fenofibrate alleviate these symptoms by promoting peroxisome proliferation and restoring epithelial repair. These findings provide insights into the GI pathogenesis of long COVID and highlight the therapeutic potential of enhancing the VLCFA-PPAR-peroxisome axis to mitigate persistent GI complications.},
}
@article {pmid41494490,
year = {2026},
author = {Messina, A and Bella, F and Maccarone, G and Avincola, G and Signorelli, MS},
title = {Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review.},
journal = {Journal of psychiatric research},
volume = {194},
number = {},
pages = {164-173},
doi = {10.1016/j.jpsychires.2026.01.007},
pmid = {41494490},
issn = {1879-1379},
mesh = {Humans ; *COVID-19/complications/immunology/pathology ; *Astrocytes/pathology/immunology/metabolism ; *Hippocampus/pathology/physiopathology/metabolism/virology/immunology ; SARS-CoV-2 ; *Neuroinflammatory Diseases ; *Cognitive Dysfunction/etiology ; *Executive Function/physiology ; },
abstract = {SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus-crucial for memory, emotional regulation, and executive functioning-is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood-brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances-most notably fatigue, apathy, low mood, and executive dysfunction-that typify dysexecutive syndrome in long-COVID. This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination-particularly its capacity to modulate microglial activation and support hippocampal neurogenesis-are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches. Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.},
}
@article {pmid41494204,
year = {2026},
author = {Shahbazi Khamas, S and Noij, LCE and Blankestijn, JM and Lap, CR and van Houten, MA and Biesbroek, G and Maitland-van der Zee, AH and Abdel-Aziz, MI and van Goudoever, JB and Alsem, MW and Brackel, CLH and Oostrom, KJ and Hashimoto, S and Brinkman, P and Terheggen-Lagro, SWJ},
title = {Exhaled breath-based clusters in children with post-COVID condition.},
journal = {Journal of breath research},
volume = {20},
number = {1},
pages = {},
doi = {10.1088/1752-7163/ae33e1},
pmid = {41494204},
issn = {1752-7163},
mesh = {Humans ; Female ; Breath Tests/methods ; Male ; Child ; *COVID-19/complications/metabolism ; *Volatile Organic Compounds/analysis/metabolism ; Biomarkers/analysis/metabolism ; Adolescent ; Exhalation ; SARS-CoV-2 ; Cluster Analysis ; Child, Preschool ; },
abstract = {Pediatric post-COVID condition (PPCC) presents as a heterogeneous disease with a broad spectrum of symptoms. This study aimed to identify distinct phenotypes of PPCC through an unbiased cluster analysis of exhaled metabolites, with the goal of identifying biomarkers to stratify patients. Exhaled breath samples were collected from children with physician-diagnosed PPCC. An unsupervised clustering approach was applied to the exhaled breath metabolites, and the resulting clusters were compared with clinical variables. Sparse partial least squares-discriminant analysis (sPLS-DA) was applied to find most discriminative metabolites between clusters. A total of 54 children were included and categorized into two clusters. Compared to Cluster 1 (n= 38), Cluster 2 (n= 16) consisted predominantly of older girls (69%) with a median age of 16 years and exhibited more severe PPCC-related outcomes, including higher PROMIS fatigue scores. Six volatile organic compounds (VOCs) were identified as biomarkers that effectively differentiated the two clusters. These VOCs, previously reported in the literature, highlight metabolic and inflammatory disruptions and demonstrated high discriminatory performance (area under the receiver operating characteristic curve (AUROCC) = 1). This study found two distinct phenotypes of PPCC, and identified six discriminating VOCs, underscoring the potential of VOCs as non-invasive biomarkers for disease stratification in PPCC. While it could be a building block towards a better understanding of the metabolic disruptions underlying PPCC, further research with larger patient cohorts is necessary to elucidate the mechanisms driving these differences.},
}
@article {pmid41493630,
year = {2026},
author = {Goretzki, SC and Bergelt, M and Weis, L and Hojeii, R and Gauß, G and Götte, M and Beller, R and Benson, S and Schönecker, A and Marina, AD and Gangfuß, A and Stehling, F and Pentek, C and von Loewenich, A and Hühne, T and Held, C and Voigt, S and Felderhoff-Müser, U and Schündeln, MM and Bruns, N and Eckert, K and Dohna-Schwake, C and Brasseler, M},
title = {Individualized online exercise therapy aids recovery in pediatric long-COVID-findings from an exploratory randomized controlled trial.},
journal = {European journal of pediatrics},
volume = {185},
number = {1},
pages = {54},
pmid = {41493630},
issn = {1432-1076},
mesh = {Humans ; Child ; Adolescent ; Female ; Male ; *COVID-19/rehabilitation ; Quality of Life ; *Exercise Therapy/methods ; Prospective Studies ; Treatment Outcome ; SARS-CoV-2 ; Feasibility Studies ; Walk Test ; Telemedicine ; },
abstract = {UNLABELLED: The purpose of this study is to evaluate the feasibility, safety, and effectiveness of an individualized online exercise therapy (IOET) designed to improve physical capacity and quality of life in children and adolescents with long-COVID. In a prospective, randomized, single-center exploratory trial, 14 patients aged 9-17 years with long-COVID (median symptom duration: 21 months) received either 6 or 12 weeks of IOET. Sessions were held twice weekly via telemedicine and individually adapted to physical ability and symptoms. Primary outcomes were functional performance (6-minute walk test [6MWT], sit-to-stand test [STST], and handgrip strength test [HST]). Secondary outcomes included school attendance, quality of life (PedsQL), safety, and self-reported recovery. All participants showed clinically improvements. In the 12-week IOET group, 6MWT increased from 396.0 to 616.3 m (+ 220.3 m, 95% CI 98.2-342.4), STST from 25.4 to 32.6 repetitions (+ 7.2, 1.9-12.5), and HST from 16.6 to 27.1 kg (+ 10.5 kg, 4.8-16.1). The 6-week group improved comparably (6MWT: 429.0 m to 601.6 m, (+ 172.6 m, 64.7-280.6); STST: 21.6 to 31.7 (+ 10.1, 3.1-17.1); HST: 17.3 to 22.1 kg (+ 4.8 kg (0.7-8.9)). School attendance rose from 58 to 97%, and PedsQL reflected improved quality of life and reduced fatigue. No adverse events or post-exertional symptom exacerbations occurred. Improvements persisted at the 3-month follow-up.<br><br>CONCLUSIONS: &#xa0;IOET is feasible, safe, and associated with improved physical function, reintegration in everyday life, and its quality in pediatric long-COVID. These findings highlight IOET as a promising rehabilitation strategy and justify larger multicenter trials to confirm effectiveness and define optimal duration.<br><br>WHAT IS KNOWN: &#x2022; Children and adolescents with long-COVID often experience persistent fatigue, impaired physical capacity, and reduced quality of life, with limited evidence-based treatment options available. &#x2022; Exercise therapy has shown beneficial effects in other chronic pediatric conditions such as cancer- or fatigue-related syndromes, improving strength, well-being, and social participation.<br><br>WHAT IS NEW: &#x2022; This exploratory randomized controlled trial demonstrates that individualized online exercise therapy is feasible, safe, and associated with clinically relevant improvements in physical function, quality of life, and school attendance in pediatric long-COVID, without negative side effects. &#x2022; The findings highlight the potential of telemedicine-based rehabilitation strategies as accessible and effective treatment approaches for children and adolescents with post-infectious conditions such as long-COVID.},
}
@article {pmid41491558,
year = {2025},
author = {Liu-Galvin, R and Orlando, FA and Mainous, AG},
title = {Economic Burden of Long COVID: Lost Labor Costs in US Adults.},
journal = {Journal of the American Board of Family Medicine : JABFM},
volume = {38},
number = {5},
pages = {940-943},
doi = {10.3122/jabfm.2025.250059R1},
pmid = {41491558},
issn = {1558-7118},
mesh = {Humans ; *COVID-19/economics/epidemiology ; United States/epidemiology ; Adult ; Female ; *Cost of Illness ; Male ; Middle Aged ; *Sick Leave/economics/statistics &amp; numerical data ; SARS-CoV-2 ; *Absenteeism ; Young Adult ; },
abstract = {INTRODUCTION: Long COVID (LC) is associated with significantly more days of work missed due to illness. Given this impact on the workforce, we estimated the lost labor costs associated with these additional missed workdays among individuals with LC in the US in 2022.<br><br>METHODS: 104,889,622 (weighted) adult full-time workers in the 2022 Medical Expenditure Panel Survey were categorized as: never had COVID-19, had COVID-19 without LC, and had LC. The estimated cost of lost labor from days of work missed due to illness/injury in 2022 was calculated as: (hours worked per week &#xf7; 5) &#xd7; (hourly wage) &#xd7; (days of work missed). Differences in mean costs were assessed using one-way ANOVA. The population-level lost labor cost associated with LC was estimated as (mean lost labor cost for LC - mean lost labor cost for never had COVID-19) &#xd7; (number of full-time workers &#x2265;18 years in the US in 2022 &#xd7; prevalence of LC in the study population).<br><br>RESULTS: The total estimated lost labor cost from days of work missed due to illness/injury for individuals with LC was $15,863,994,281 (SE, $1,748,160,632). The mean lost labor cost for individuals with LC was more than twice that of individuals who never had COVID-19 and significantly higher than those who had COVID-19 without LC. The population-level lost labor cost associated with LC was estimated to be $12,784,168,675.20 (SE, $1,946,074,821.60).<br><br>DISCUSSION: These findings highlight the substantial economic impact of LC, totaling more than $12 billion in lost labor costs in 2022, emphasizing the need for targeted prevention and treatment strategies.},
}
@article {pmid41490577,
year = {2026},
author = {Wilson, M and Pedersen, SG and Langeland, N and Cox, RJ and Aukrust, P and Dahl, TB and Sandvig, A and Wilhelmsen, M},
title = {Tailored Individual Follow-Ups Versus a One-Day Group Course in Patients With Long COVID (Post- COVID-19 Condition): Protocol for a Randomized Controlled Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e74113},
pmid = {41490577},
issn = {1929-0748},
mesh = {Humans ; *COVID-19/rehabilitation/complications ; Adult ; Middle Aged ; Quality of Life ; Aged ; Adolescent ; Young Adult ; Male ; Female ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; Mobile Applications ; Self-Management/methods ; Post-Acute COVID-19 Syndrome ; Equivalence Trials as Topic ; },
abstract = {BACKGROUND: The high prevalence of patients with post-COVID-19 condition, also called long COVID, even among those with mild initial disease, may have a large impact on both the individual and society. Disability in everyday life, reduced health-related quality of life and work capacity, strain on the health care system, and substantial socioeconomic costs are associated with long COVID. More research to investigate the effectiveness of rehabilitation services is warranted.<br><br>OBJECTIVE: This study aims to examine the effectiveness of tailored individual follow-ups versus a 1-day group course in patients with long COVID. Additionally, the feasibility and use of a mobile app for self-monitoring goal achievement will be assessed.<br><br>METHODS: This is a single-center, parallel-group, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 62 outpatients aged 18-65 years with long COVID will be randomized to either a rehabilitation program with individual follow-up consultations or a 1-day self-management group course. The individual intervention incorporates setting goals, teaching cognitive behavioral strategies, energy management (pacing), and a supervised gradual increase in both physical and cognitive activities tailored to individual tolerance levels. The primary outcome is the between-group difference in health-related quality of life, measured using the EQ-5D-5L index at 6 months. Secondary outcomes include improvements in symptoms, work participation, neurocognitive function, and app usability, assessed at 3, 6, and 12 months, depending on the outcome measure.<br><br>RESULTS: Data enrollment started in October 2023. A total of 62 participants were included by November 2024. Data collection is planned to be completed in November 2025.<br><br>CONCLUSIONS: Long COVID poses substantial challenges for both individuals and society, underscoring the need for effective rehabilitation strategies. This study will provide valuable insights into the benefits of an individualized outpatient rehabilitation program. The results from this clinical trial will help guide future treatment recommendations and may improve long-term outcomes for affected patients. Additionally, the study will generate important knowledge about neuropsychological function and digital self-management tools in long COVID rehabilitation.},
}
@article {pmid41490011,
year = {2026},
author = {Rhee, KE and Thaweethai, T and Pant, DB and Stein, CR and Salisbury, AL and Kinser, PA and Kleinman, LC and Gallagher, R and Warburton, D and Mohandas, S and Snowden, JN and Stockwell, MS and Tantisira, KG and Flaherman, VJ and Teufel, RJ and Castro, L and Chung, A and Espinoza Esparza, J and Hockett, CW and Isidoro-Chino, M and Krishnan, A and McCormack, LA and Nabower, AM and Nahin, ER and Rosas, JM and Siddiqui, S and Szmuszkovicz, JR and Vangeepuram, N and Zimmerman, E and Brown, HE and Carmilani, M and Coombs, K and Fisher, L and Witvliet, MG and Wood, JC and Milner, JD and Rosenzweig, EB and Irby, K and Karlson, EW and Qian, Z and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, HS and Foulkes, AS and Gross, RS and , and Aschner, JL and Atz, AM and Banerjee, D and Bogie, A and Bukulmez, H and Clouser, K and Cottrell, LA and Cowan, K and D'Sa, VA and Dozor, AJ and Elliott, AJ and Faustino, EVS and Fiks, AG and Gaur, S and Gennaro, ML and Gordon, ST and Hasan, UN and Hester, CM and Hogan, AH and Hsia, DS and Kaelber, DC and Kosut, JS and Krishnan, S and McCulloh, RJ and Michelow, IC and Nolan, SM and Oliveira, CR and Pace, WD and Palumbo, P and Raissy, H and Reyes, A and Ross, JL and Salazar, JC and Selvarangan, R and Stevenson, MD and Werzberger, A and Westfall, JM and Zani, K and Zempsky, WT and Chan, J and Metz, TD and Newburger, JW and Truong, DT and Feldman, CH and Aupperle, R and Baker, FC and Banich, MT and Barch, DM and Baskin-Sommers, A and Bjork, JM and Dapretto, M and Brown, SA and Casey, BJ and Chang, L and Clark, DB and Dale, AM and Ernst, TM and Fair, DA and Feldstein Ewing, SW and Foxe, JJ and Freedman, EG and Friedman, NP and Garavan, H and Gee, DG and Gonzalez, R and Gray, KM and Heitzeg, MM and Herting, MM and Jacobus, J and Laird, AR and Larson, CL and Lisdahl, KM and Luciana, M and Luna, B and Madden, PAF and McGlade, EC and Müller-Oehring, EM and Nagel, BJ and Neale, MC and Paulus, MP and Potter, AS and Renshaw, PF and Sowell, ER and Squeglia, LM and Uddin, LQ and Wilson, S and Yurgelun-Todd, DA},
title = {Social Determinants of Health and Pediatric Long COVID in the US.},
journal = {JAMA pediatrics},
volume = {180},
number = {3},
pages = {275-287},
pmid = {41490011},
issn = {2168-6211},
support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; U01 DA041120/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Social Determinants of Health/statistics &amp; numerical data ; Child ; *COVID-19/epidemiology ; Male ; Adolescent ; Cross-Sectional Studies ; United States/epidemiology ; Female ; Longitudinal Studies ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {IMPORTANCE: Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID.<br><br>OBJECTIVE: To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US.<br><br>This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n&#x2009;=&#x2009;903) and adolescents (12-17 years; n&#x2009;=&#x2009;3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024.<br><br>EXPOSURE: Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models.<br><br>MAIN OUTCOMES AND MEASURES: Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices.<br><br>RESULTS: The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results.<br><br>CONCLUSIONS AND RELEVANCE: In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.},
}
@article {pmid41488386,
year = {2026},
author = {Cash, N and Koebel, MC and Badran, BW and Schumann, AY and McTeague, LM and Uhde, TW and Schlosser, RJ and Cortese, BM},
title = {Study of Chemosensory Enhancement through Neuromodulation Training (SCENT): Design and methodology of a randomized clinical trial for COVID-related persistent smell dysfunction.},
journal = {Contemporary clinical trials communications},
volume = {49},
number = {},
pages = {101582},
pmid = {41488386},
issn = {2451-8654},
support = {R01 DC021179/DC/NIDCD NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Few evidence-based treatments exist for COVID-related persistent smell dysfunction. While smell/olfactory training (ST) has emerged as a widely prescribed, first line treatment, rigorous study is required to determine its efficacy in Long COVID. Additional study and development of adjunctive methods to improve the efficacy of ST is also needed.<br><br>METHODS: This paper details the study design and methodology for a large, at-home, randomized, controlled trial designed to determine whether ST and/or trigeminal nerve stimulation (TNS)-enhanced ST improves Long COVID-related disturbances in smell function, mood, sleep, and cognition. Adults with COVID-related persistent smell dysfunction (N&#xa0;=&#xa0;180) will be recruited and randomized to self-administer ST, placebo smell training (PBO), or TNS-enhanced ST daily for 12 weeks. Our primary objectives are to i) determine the efficacy of ST, compared to any natural gain in function, on olfactory-specific deficits, ii) determine the TNS-enhanced effects of ST on olfactory-specific deficits, and iii) determine if TNS-enhanced ST, compared to ST, is also more efficacious in the treatment of other symptoms of Long COVID.<br><br>CONCLUSION: Post COVID persistent smell dysfunction and related deficits are relatively common with very few treatment options. Our proposed study will lay the groundwork for further development of ST and TNS as evidence-based treatments for Long COVID.},
}
@article {pmid41488148,
year = {2025},
author = {Shitaye, G and Getie, M and Mekonnen, Z and D'Abrosca, G and Fattorusso, R and Isernia, C and Amuamuta, A and Malgieri, G},
title = {Molecular analysis of long COVID and new-onset diabetes mellitus: pathobiological relationships and current mechanistic views.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1737894},
pmid = {41488148},
issn = {1664-2392},
mesh = {Humans ; *COVID-19/complications/metabolism/pathology/epidemiology ; *SARS-CoV-2 ; *Diabetes Mellitus, Type 2/epidemiology/etiology/virology/metabolism/pathology ; *Diabetes Mellitus, Type 1/epidemiology/metabolism/etiology/virology ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; Insulin Resistance ; },
abstract = {Long COVID, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), refers to a range of persistent health effects associated with SARS-CoV-2 infection. Long COVID is a complex, multisystem disorder that can affect nearly every organ system and is strongly linked with the incidence of diabetes and other chronic conditions. Increasing evidence also connects persistent SARS-CoV-2 infection with the development of new-onset diabetes and other metabolic disorders. In this review, we assess the current evidence and discuss the incidence of new-onset diabetes, along with the pathobiological mechanisms by which SARS-CoV-2 may contribute to the progression of both new-onset type 1 and type 2 diabetes mellitus (T1DM and T2DM). We summarize the latest understanding of the molecular and cellular mechanisms underlying SARS-CoV-2-associated new-onset diabetes. Potential mechanisms include direct damage to pancreatic β-cells, inflammation, insulin resistance, and autoimmune responses. Dysregulation of the ACE2/renin-angiotensin system (RAS) pathway has been linked to multiple inter-organ pathologies, and increased inflammatory cytokines together with dysregulation of interferon regulatory factors (IRFs)-such as overexpression of IRF1-appear to represent key mechanistic links to widespread tissue damage and metabolic alterations. Moreover, the presence of viral RNA or viral RNA fragments may directly damage pancreatic islets, contributing to insulin resistance and β-cell dysfunction that, in turn, may promote the development of new-onset diabetes. In light of these findings, this review further examines evidence supporting the persistence of SARS-CoV-2 RNA in PASC reservoir tissues, including the pancreas, and its potential association with the development of new-onset diabetes mellitus.},
}
@article {pmid41487856,
year = {2025},
author = {Van Cleve, R and Lienau, A and Sanchez Garcia, J},
title = {Elevated Risk of an Emergency Department Admission Associated With Long COVID Diagnosis Within the US Veteran Population.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e98410},
pmid = {41487856},
issn = {2168-8184},
abstract = {Long COVID has emerged as a significant public health concern, potentially affecting millions of people over the next decade. By examining the risk of an emergency department (ED) visit associated with long COVID across a population, we can see the population-level severity of long COVID. This study aims to quantify the change in risk for ED visits in the six months following COVID-19 infection for people diagnosed with long COVID compared to those who are only infected with COVID-19 but not diagnosed with long COVID. The study compared the risk of an ED visit between veterans with long COVID and those with only COVID-19 infection. We examined the risk of an ED visit for these two groups in the six months before and the six months after being infected with COVID-19. Data came from the Veterans Health Administration (VHA) electronic medical records, specifically veterans who used the Veterans Affairs (VA) healthcare system and had an initial case of COVID-19 between March 1, 2021, and December 21, 2021. We examined ER visits six months before and after testing positive for COVID-19. The outcome of interest was the risk of an ED visit for people diagnosed with long COVID compared to people who only contracted COVID-19 and were not diagnosed with long COVID. In the six months after contracting long COVID, veterans eventually diagnosed with long COVID had a 34% higher risk of ED visits compared to those who contracted COVID-19 but never developed long COVID. Between three and six months post-infection, the risk of ED visits was 21% higher in the long COVID group. Long COVID can be a severe condition whose effects can last months after infection and diagnosis. Certain policies need to be implemented to manage the symptoms of this disease and reduce the need for emergency department services.},
}
@article {pmid41486438,
year = {2025},
author = {Seo, JW and Seo, YB and Kim, SE and Kim, Y and Kim, EJ and Kim, T and Kim, T and Lee, SH and Lee, E and Lee, J and Jeong, YH and Jung, YH and Choi, YJ and Song, JY},
title = {Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19.},
journal = {Infection &amp; chemotherapy},
volume = {57},
number = {4},
pages = {478-521},
pmid = {41486438},
issn = {2093-2340},
support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; },
abstract = {The guidelines presented herewith are based on the "Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19 (PASC)" published in Infection &amp; Chemotherapy in March 2024; these guidelines have been refined by incorporating the most recent Korean and international research findings and clinical evidence published since then. In the context of patients experiencing various physical and mental symptoms that persist long after the acute phase of coronavirus disease 2019 (COVID-19) infection, the diagnosis and management of PASC has emerged as a novel public health challenge. These guidelines are intended to provide standardized diagnostic and management recommendations applicable to the Korean healthcare setting and were developed through a comprehensive review of existing guidelines from organizations such as the World Health Organization, the United States National Institutes of Health, the United Kingdom National Institute for Health and Care Excellence, and the European Society of Clinical Microbiology and Infectious Diseases, along with the latest meta-analyses and Korean cohort studies. PASC is defined as the persistent presence of symptoms and signs lasting more than 3 months after COVID-19 diagnosis for which the symptoms cannot be explained by alternative diagnoses. The revised guidelines emphasize the importance of integrated management for patients with PASC, including a multidisciplinary approach considering risk groups, symptom-specific assessment, and rehabilitation and psychological interventions, based on a total of 32 key questions. This revision reflects rapidly evolving research trends regarding the long-term effects of COVID-19 and is expected to serve as an evidence-based standard guideline for future patient care, clinical research, and health policy development in Korea.},
}
@article {pmid41485406,
year = {2026},
author = {Case, SJ and Sabik, L and Grant, H},
title = {Factors associated with long COVID among cancer survivors: A population-based analysis.},
journal = {Cancer epidemiology},
volume = {100},
number = {},
pages = {102984},
doi = {10.1016/j.canep.2025.102984},
pmid = {41485406},
issn = {1877-783X},
mesh = {Humans ; Male ; Female ; *Cancer Survivors/statistics &amp; numerical data ; *COVID-19/epidemiology/virology ; Middle Aged ; Cross-Sectional Studies ; Aged ; Adult ; SARS-CoV-2/isolation &amp; purification ; *Neoplasms/epidemiology/therapy ; Risk Factors ; Prevalence ; Behavioral Risk Factor Surveillance System ; Young Adult ; Comorbidity ; },
abstract = {INTRODUCTION: Cancer survivors endure unique immune system suppression as a result of their cancer treatment, potentially making them susceptible to long COVID in ways that differ from the general population. The purpose of this study is to assess what factors are associated with long COVID among cancer survivors.<br><br>METHODS: Observational, cross-sectional data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS) survey were analyzed. The main outcome of interest was the prevalence of long COVID among cancer survivors who had tested positive for COVID-19. Bivariate analyses were conducted comparing those who did and did not have long COVID, and logistic regression models were used to determine the sociodemographic variables and individual health factors associated with long COVID among cancer survivors.<br><br>RESULTS: In this sample, 15.2&#x202f;% of cancer survivors who had tested positive for COVID-19 indicated they had long COVID. Cancer survivors who were male, older, received flu and COVID-19 vaccinations, and did not have diabetes or asthma had significantly lower odds of having long COVID.<br><br>CONCLUSION: This study provides insight into what sociodemographic and health-related factors are associated with the presence of long COVID, including age, sex, vaccination status, and comorbid conditions. Future longitudinal studies are warranted to establish causal patterns.},
}
@article {pmid41484677,
year = {2026},
author = {White, RA and Salamanca, BV and Angelsen, A and Zakiudin, DP and Andries, A and Nyborg, GA},
title = {Excess primary healthcare consultations in Norway in 2024 compared to pre-COVID-19-pandemic baseline trends.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {84},
number = {1},
pages = {26},
pmid = {41484677},
issn = {0778-7367},
abstract = {BACKGROUND: The risk of post-acute sequelae of COVID-19 (PASC) is estimated at 3-6% per infection in 2024. We hypothesized that widespread SARS-CoV-2 infections could lead to population-level consequences. Our previous study identified substantial increases in Norwegian primary healthcare consultations in 2023-compared to pre-pandemic levels-for conditions associated with acute COVID-19 and PASC. This study extended that analysis to 2024. We then assessed whether observed patterns were compatible with our hypothesis.<br><br>METHODS: We used data from the Norwegian Syndromic Surveillance System, which captures nationwide primary healthcare consultations for 102 ICPC-2 codes (out of a possible 710) that are relevant for infectious disease surveillance and some post-acute infection syndromes. Bayesian linear regression models were fitted to 2010-2019 trends, adjusting for population changes, to estimate expected values for 2024. Excess consultations were calculated by age and sex. A COVID-19 community spread was proxied by vaccination-adjusted weekly hospitalization rates.<br><br>RESULTS: In 2024, there were 17,800,365 consultations, corresponding to an absolute excess of 1,185,231 consultations, or a 7.1% relative excess, compared to the modelled baseline. The 10 code combinations with largest absolute excess in 2024 were respiratory infections (325,726 excess consultations; 20% relative excess), fatigue (205,381; 70%), psychological symptom/complaint other (188,978; 87%), acute stress reaction (182,079; 76%), feeling depressed (126,783; 133%), hyperkinetic disorder (112,763; 116%), abdominal pain/cramps general (84,544; 29%), memory disturbance (39,177; 63%), conjunctivitis (34,643; 59%), and infectious disease other/NOS (33,556; 81%). COVID-19 community spread showed the strongest correlations with conjunctivitis, strep throat, respiratory infections as a group (R**), fatigue, infectious disease other, memory disturbances, and pneumonia. Deviations from pre-pandemic trends varied: respiratory and psychological disorders worsened from 2020 onward and several conditions showed dramatic excess from 2022-2024. Females 15-29, children, adolescents, and young adults had disproportionately large relative excesses for consultations for memory disturbances.<br><br>CONCLUSIONS: Primary healthcare consultations in 2024 significantly exceeded pre-pandemic expectations, especially for conditions linked to acute COVID-19 and PASC, though the two cannot be differentiated in these data. While other factors undoubtedly also play a role, findings are compatible with ongoing population-level health impacts associated with repeated SARS-CoV-2 infections, particularly among women, children, adolescents, and young adults. These results emerged under a national COVID-19 strategy that does not account for post-acute consequences of SARS-CoV-2 infection.},
}
@article {pmid41484589,
year = {2026},
author = {Kamdem, OL and Dupre, C and Guyot, J and Ruiz, L and Nekaa, M and Botelho-Nevers, E and Bongue, B},
title = {Task delegation in emerging chronic diseases: Long COVID care as a paradigm - a cross-sectional study.},
journal = {BMC nursing},
volume = {25},
number = {1},
pages = {104},
pmid = {41484589},
issn = {1472-6955},
support = {Grant number: ANRS283//ANRS - Agence Nationale de la Recherche / Emerging Infectious Diseases./ ; },
abstract = {BACKGROUND: Emerging chronic diseases like Long COVID challenge traditional care models, creating therapeutic voids that nurses spontaneously fill through informal task delegation. This study examines nursing roles delegated in Long COVID care and identifies implications for nursing administration.<br><br>METHODS: A cross-sectional study was conducted among 362 nurses in France&#x2019;s Rh&#xf4;ne-Alpes region (December 2023-March 2024). An online questionnaire assessed Long COVID care roles and delegation patterns.<br><br>RESULTS: Among participants, 39.8% (95% CI: 34.8&#x2013;44.9%) had cared for Long COVID patients. Primary delegated roles included psychological support (86.8%, 95% CI: 80.0-91.8%), proximity care (72.9%), screening/detection (42.4%, 95% CI: 34.2&#x2013;50.9%), and therapeutic education (70.8%). Nurses performing screening roles were significantly more likely to also perform coordination activities (OR&#x2009;=&#x2009;3.87, 95% CI: 1.92&#x2013;7.80, p&#x2009;<&#x2009;0.001) and therapeutic education (OR&#x2009;=&#x2009;5.63, 95% CI: 2.37&#x2013;13.36, p&#x2009;<&#x2009;0.001). Private practice nurses demonstrated significantly greater task appropriation. Despite the quasi-total absence of specific training (1.4%), 80.4% (95% CI: 73.1&#x2013;86.3%) of nurses with Long COVID care experience declare themselves ready to formally assume coordination responsibilities for Long COVID patient pathways.<br><br>CONCLUSIONS: Nurses spontaneously appropriate medical roles when confronting emerging diseases. Nursing administration must formalize this informal delegation through structured training and policy frameworks to optimize chronic disease management. The screening role assumed by nurses represents a significant evolution in diagnostic responsibilities distribution, requiring recognition and structured support.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12912-025-04249-5.},
}
@article {pmid41484172,
year = {2026},
author = {Doni Jayavelu, N and Samaha, H and Wimalasena, ST and Hoch, A and Gygi, JP and Gabernet, G and Ozonoff, A and Liu, S and Milliren, CE and Levy, O and Baden, LR and Melamed, E and Ehrlich, LIR and McComsey, GA and Sekaly, RP and Cairns, CB and Haddad, EK and Schaenman, J and Shaw, AC and Hafler, DA and Montgomery, RR and Corry, DB and Kheradmand, F and Atkinson, MA and Brakenridge, SC and Agudelo Higuit, NI and Metcalf, JP and Hough, CL and Messer, WB and Pulendran, B and Nadeau, KC and Davis, MM and Geng, LN and Fernandez Sesma, A and Simon, V and Krammer, F and Kraft, M and Bime, C and Calfee, CS and Erle, DJ and Langelier, CR and , and Guan, L and Maecker, HT and Peters, B and Kleinstein, SH and Reed, EF and Augustine, AD and Diray-Arce, J and Becker, PM and Rouphael, N and Altman, MC},
title = {Machine learning models predict long COVID outcomes based on baseline clinical and immunologic factors.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {1},
pmid = {41484172},
issn = {2730-664X},
support = {U19 AI090023/AI/NIAID NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; U19 AI118608/AI/NIAID NIH HHS/United States ; U54 AI142766/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; U19 AI062629/AI/NIAID NIH HHS/United States ; U19 AI077439/AI/NIAID NIH HHS/United States ; S10 OD026799/OD/NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; U19 AI128910/AI/NIAID NIH HHS/United States ; R01 AI104870/AI/NIAID NIH HHS/United States ; U19 AI125357/AI/NIAID NIH HHS/United States ; R01 AI145835/AI/NIAID NIH HHS/United States ; U19 AI128913/AI/NIAID NIH HHS/United States ; R01 AI132774/AI/NIAID NIH HHS/United States ; R01 AI135803/AI/NIAID NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID, remain a significant health issue that is incompletely understood. Predicting which acutely infected individuals will develop long COVID is challenging due to the absence of established biomarkers, clear disease mechanisms, or well-defined sub-phenotypes. Machine learning (ML) models may address this gap by leveraging clinical data to enhance diagnostic precision.<br><br>METHODS: Clinical data, including antibody titers and viral load measurements collected at the time of hospital admission, are used to predict the likelihood of acute COVID-19 progressing to long COVID. Machine learning models are trained and evaluated for predictive performance. Feature importance analysis is performed to identify the most influential predictors.<br><br>RESULTS: The machine learning models achieve median AUROC values ranging from 0.64 to 0.66 and AUPRC values between 0.51 and 0.54, demonstrating predictive capabilities. Low antibody titers and high viral loads at hospital admission emerge as the strongest predictors of long COVID outcomes. Comorbidities-such as chronic respiratory, cardiac, and neurologic diseases-and female sex are also identified as significant risk factors.<br><br>CONCLUSIONS: Machine learning models identify patients at risk for developing long COVID based on baseline clinical characteristics. These models guide early interventions, improve patient outcomes, and mitigate the long-term public health impacts of SARS-CoV-2.},
}
@article {pmid41483427,
year = {2026},
author = {Schwartz, CE and Borowiec, K},
title = {Toward characterizing brain fog in long COVID: correlates and impact on measurement metrics.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {1},
pages = {22},
pmid = {41483427},
issn = {1573-2649},
}
@article {pmid41482843,
year = {2026},
author = {Duru, EE and Okoye, G and Lee, S and Weir, P and Kim, J},
title = {Comparison of Healthcare Expenditures Among Individuals With and Without Long COVID in the United States.},
journal = {Inquiry : a journal of medical care organization, provision and financing},
volume = {63},
number = {},
pages = {469580251410890},
pmid = {41482843},
issn = {1945-7243},
mesh = {Humans ; *Health Expenditures/statistics &amp; numerical data ; United States/epidemiology ; *COVID-19/economics/epidemiology/therapy ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; SARS-CoV-2 ; Young Adult ; Hospitalization/economics/statistics &amp; numerical data ; },
abstract = {Long COVID increases healthcare utilization, yet differences in healthcare spending patterns between individuals with and without long COVID remain poorly characterized, especially at the national level. To evaluate differences in healthcare expenditures among U.S. adults with and without long COVID using nationally representative data. This cross-sectional study analyzed data from the 2022 Medical Expenditure Panel Survey (MEPS), including 16 762 unweighted adults (weighted population: 239 915 159). Healthcare spending outcomes included total expenditures and specific categories including office-based care, outpatient services, emergency room visits, hospital admissions, home healthcare, and prescription medications. A survey-weighted generalized linear model (GLM) with a log link and gamma distribution was used to estimate adjusted differences in expenditures between groups. Individuals with long COVID had significantly higher total healthcare expenditures (mean $11 567; SD $25 334) compared to those without long COVID ($7448; SD $21 734, P < .01). After adjusting for demographic characteristics, insurance status, chronic conditions, and other potential confounders, individuals with long COVID incurred 40% higher total expenditures (β = 1.40, P = .01). Expenditures were significantly elevated for office-based visits (35% higher; β = 1.35, P = .02) and outpatient services (118% higher; β = 2.18, P < .01). No significant differences were found in emergency room, hospital admissions, or dental care expenditures. Long COVID imposes a substantial financial burden on individuals and healthcare systems, primarily through increased outpatient and office-based service utilization. Understanding these spending patterns can help inform policy decisions, optimize healthcare resource allocation, and guide targeted interventions to manage long COVID more effectively.},
}
@article {pmid41482551,
year = {2026},
author = {},
title = {A role for chronic inflammation in long COVID.},
journal = {Nature immunology},
volume = {27},
number = {1},
pages = {12-13},
pmid = {41482551},
issn = {1529-2916},
}
@article {pmid41481665,
year = {2026},
author = {Martoreli Júnior, JF and O Pedroso, A and Lima, LDES and P Gusmão, CM and G Menegueti, M and F C Coêlho, H and Zamarioli, CM and Silva, ACOE and R O Naiff, G and Gir, E and K Reis, R},
title = {Prevalence and associated factors with long COVID in the Brazilian population: The role of health-related behaviors and sociodemographic characteristics.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0339612},
pmid = {41481665},
issn = {1932-6203},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; Prevalence ; Adult ; Cross-Sectional Studies ; Aged ; SARS-CoV-2/isolation &amp; purification ; Risk Factors ; *Health Behavior ; Young Adult ; Adolescent ; Sociodemographic Factors ; },
abstract = {The disease caused by the 2019 coronavirus (COVID-19) has resulted in unprecedented morbidity and mortality worldwide, with many individuals experiencing persistent symptoms and a decline in quality of life after infection. This study aims to analyze the prevalence and associated factors of long COVID in the Brazilian population, focusing on disease severity and immunization status. This observational, cross-sectional web survey employed a quantitative approach to analyze data from 4,231 participants, focusing on the prevalence and associated factors of long COVID. Data were analyzed using inferential statistical methods to identify factors associated with the outcome. A multivariable logistic regression model was applied to determine the variables independently associated with long COVID. To determine the best model, a stepwise selection method was employed, and the model's performance was assessed utilizing a Receiver Operating Characteristic Curve (ROC). The findings revealed a long COVID prevalence of 56.4% (2,386 cases), with men having a 36.46% (OR = 1,36 CI = 1,17-1,58) higher chance of developing long COVID compared to women. A prior diagnosis before vaccination increased by 22.30% (OR = 1,22 CI = 1,05-1,41). Additionally, the use of sedatives and alcohol was linked to increases of 24.50% (OR = 1,24 CI = 1,07-1,43) and 34.95% (OR = 1,34 CI = 1,02-1,75), respectively. Beneficiaries of social programs faced a 47.29% (OR = 1,47 CI = 1,27-1,70) higher, while individuals with comorbidities had a 33.47% (OR =1,33 CI = 1,20-1,48). Hospitalization significantly raised the likelihood of prolonged symptoms by 331.92% (OR = 4,31 CI = 2,53-7,87). Overall, various factors, including sedative and alcohol use, were factors associated with long COVID, whereas vaccination showed a positive impact, suggesting that association models can help healthcare professionals identify high-risk patients and tailor care effectively.},
}
@article {pmid41480529,
year = {2025},
author = {Escrivá, N and Moreno-Galarraga, L and Barado, E and Torres, MG and Fernández-Montero, A},
title = {Assessment of long COVID-19 symptoms and functional status: insights from a cross-sectional study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1715786},
pmid = {41480529},
issn = {2296-858X},
abstract = {This cross-sectional study examines the functional limitations of Long COVID (LC) in a clinically confirmed cohort (n = 220). We collected sociodemographic, clinical, and lifestyle data via a structured electronic form and assessed daily limitations using the Post-COVID-19 Functional Status (PCFS) scale. Linear models were used to evaluate the association between symptom burden and functional limitations and to identify symptom-specific predictors of impairment. Participants had a mean age of 44.8 years, and 80.5% were women. A dose-response pattern linked higher symptom counts with worse PCFS grades in the multivariable-adjusted model (β = 0.17; 95% CI 0.10-0.25; p < 0.001). In hierarchical models, fatigue, dizziness, and memory loss were independent predictors of greater functional limitations (crude β: fatigue 1.56; 95% CI 1.22-1.90; dizziness 1.08; 95% CI 0.81-1.34; and memory loss 1.26; 95% CI 0.97-1.55), cumulatively explaining 51.3% of the variance in functional limitations. In contrast, other common LC symptoms did not retain independent associations after adjustment. These findings highlight the value of simple symptom counts and targeted symptom profiles for risk stratification in primary care and occupational health and for planning rehabilitation and work ability assessment. Prospective studies should validate these indicators over time and explore the mechanisms linking neurocognitive and fatigue phenotypes with persistent disability.},
}
@article {pmid41480252,
year = {2025},
author = {Salas, RL and la Asunción, M and Vásquez-Soto, C and Orta-Visbal, K and Serrano, V and Villarreal, E and Sepúlveda, S and Montalvo, MJ and Nuñez, JA and Borja, J},
title = {Scoping review of the emerging definition of long COVID: implications for future research and clinical practice.},
journal = {Revista de salud publica (Bogota, Colombia)},
volume = {27},
number = {6},
pages = {122127},
pmid = {41480252},
issn = {2539-3596},
mesh = {Humans ; *COVID-19/complications/diagnosis ; *Terminology as Topic ; Biomedical Research ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID, Post-COVID19 syndrome and prolonged COVID-19, are concepts classified as the set of signs and symptoms that persist after an acute episode of COVID-19 disease.<br><br>OBJECTIVE: To describe what definitions have been published for the term "long COVID".<br><br>METHODS: The PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) was used as a base for a scoping review, as suggested by Joanna Briggs Institute. A search of databases, Medline via PubMed, Embase, SciELO and The Cochrane Library was undertaken. The data registry and synthesis of the results was carried out independently by two reviewers.<br><br>RESULTS: Following removal of duplicates, 896 articles were retrieved of which 91 met the eligibility principles and 51 of which included a definition. At least four characteristics of the definitions were identified: time or term, organs affected, symptoms and clinical manifestations.<br><br>CONCLUSIONS: The review identified many concepts and definitions of "long COVID". These findings show that there is lack of consensus on the definition of long COVID-19.},
}
@article {pmid41477577,
year = {2025},
author = {Müllenmeister, C and Königs, G and Heinemann, S and Schröder, D and Müller, F and Hummers, E and Stölting, A and Happle, C and Dopfer-Jablonka, A and Behrens, G and Marotzki, U and Schmachtenberg, T},
title = {Acceptability of Telehealth-Delivered Occupational Therapy Among Individuals With Long COVID Using the Theoretical Framework of Acceptability: A Qualitative Study.},
journal = {International journal of telemedicine and applications},
volume = {2025},
number = {},
pages = {8879520},
pmid = {41477577},
issn = {1687-6415},
abstract = {BACKGROUND: Long COVID still challenges healthcare systems worldwide. Tailored treatments are scarce. In the ErgoLoCo study, we have developed and tested a telehealth-delivered occupational therapy intervention for people affected by long COVID. Acceptability from both recipients and providers is a prerequisite for implementing such new interventions.<br><br>AIM: This study is aimed at exploring the perceptions of people with long COVID and occupational therapists regarding the intervention's acceptability and telehealth delivery approaches.<br><br>METHODS: Semistructured interviews were conducted with 13 participants who experience long COVID and received the ErgoLoCo intervention delivered as teletherapy sessions or prerecorded videos. Eight occupational therapists who guided the teletherapy sessions participated in a focus group. Materials were analyzed following qualitative descriptive methods and interpreted using the theoretical framework of acceptability (TFA).<br><br>RESULTS: Occupational therapists and long COVID clients considered the occupational therapy approach a positive experience. While all participants in the teletherapy group found the occupational therapy approach helpful in coping with long COVID symptoms and regaining participation in meaningful occupations, perceptions varied in the group supplied with prerecorded videos. Some saw the intervention as helpful, but all emphasized the need for professional support from occupational therapists to use the program more effectively. The occupational therapists emphasized the need to tailor the therapy content to clients' needs to ensure effective and successful management of occupational challenges.<br><br>DISCUSSION: The study highlights telehealth-delivered occupational therapy's potential benefits and challenges for individuals with long COVID. It contributes to understanding the challenges and potential of telehealth-delivered occupational therapy for long COVID rehabilitation. This study's key finding is the importance of personalized and professionally guided telehealth interventions. Trial Registration: German Clinical Trial Registry identifier DRKS00029990.},
}
@article {pmid41477078,
year = {2025},
author = {Agarwal, K and Tansey, CM and Rizk, AK and Beauchamp, MK and Ross, BA and Bourbeau, J and Sedeno, M and Barreto, L and Zucco, R and Crowley, E and Janaudis-Ferreira, T},
title = {Perspectives of Individuals With Long COVID on Virtual Physical Rehabilitation: A Qualitative Study.},
journal = {Archives of rehabilitation research and clinical translation},
volume = {7},
number = {4},
pages = {100526},
pmid = {41477078},
issn = {2590-1095},
abstract = {OBJECTIVE: Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2, and long COVID is a chronic condition characterized by symptoms persisting for atleast 3 months after infection. To explore the perspectives of individuals with long COVID after an 8-week virtual physical rehabilitation program.<br><br>DESIGN: Qualitative descriptive study.<br><br>SETTING: Clinics and research cohorts.<br><br>PARTICIPANTS: Adults (n=132) with confirmed or probable COVID-19 infection and persistent symptoms, including reduced mobility, muscle weakness, dyspnea, and/or fatigue, were recruited in a randomized controlled trial. Thirteen intervention group participants who completed the rehabilitation program were included in this qualitative study.<br><br>INTERVENTIONS: The intervention group (n=65) received 8 weeks of tailored, symptom-titrated exercises, weekly educational sessions, and usual care, whereas the control group (n=67) received only usual care.<br><br>MAIN OUTCOME MEASURES: Semistructured videoconference interviews were conducted and analyzed using deductive thematic analysis.<br><br>RESULTS: Participants' age (mean &#xb1; SD) was 48.3&#xb1;15.6 years, 6 had been hospitalized during their COVID-19 infection, and the duration of long COVID (mean &#xb1; SD) was 18.8&#xb1;7.2 months. Four themes were identified: (1) Motivation and confidence: most participants expressed confidence in joining the program, motivated by health goals, scientific contribution, and reassurance from professional support. (2) Program features: the program was praised for its well-organized format, ideal duration, convenient scheduling, supportive kinesiologists, and individualized exercise plans. (3) Health effects: while most reported physical and emotional improvements (eg, increased energy, mobility, and confidence), some noted challenges upon returning to work. (4) Post-program suggestions: participants intended to continue exercising but faced barriers such as fatigue and a lack of motivation, highlighting the need for continued support and resources to maintain progress.<br><br>CONCLUSIONS: This study highlights the positive effects and relevant challenges associated with completing an 8-week personalized, symptom-titrated virtual physical rehabilitation program for individuals with long COVID, emphasizing the need for tailored support and ongoing resources to facilitate sustained recovery.},
}
@article {pmid41476972,
year = {2025},
author = {Del Carpio-Orantes, L and Zambrano-Sánchez, G},
title = {Vaccination in the post-COVID era: lessons to be learned in Latin America.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1726836},
pmid = {41476972},
issn = {1664-3224},
mesh = {Humans ; Latin America/epidemiology ; *COVID-19/prevention &amp; control/epidemiology/immunology ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Vaccination ; },
abstract = {In this document we discuss the reality of COVID vaccination in Latin America, which has been uneven across the continent; however, some experiences with COVID vaccination have demonstrated a protective effect against the development of chronic manifestations of COVID, in the so-called post-COVID syndrome.},
}
@article {pmid41476195,
year = {2025},
author = {Yeh, HW and Chaou, CH and Yang, SF and Wang, YH and Kuan, YH and Yeh, CB},
title = {SGLT2 inhibitors prevent long-COVID-associated cognitive and pain symptoms in type 2 diabetes patients.},
journal = {Virology journal},
volume = {23},
number = {1},
pages = {27},
pmid = {41476195},
issn = {1743-422X},
support = {CSH-2025-D-005//Chung Shan Medical University Hospital/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/drug therapy/complications ; Male ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Female ; Middle Aged ; *COVID-19/complications/prevention &amp; control ; Retrospective Studies ; Aged ; *Pain/prevention &amp; control ; SARS-CoV-2 ; Adult ; },
abstract = {BACKGROUND: Long COVID presents significant health challenges, especially for patients with type 2 diabetes. Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors may provide protective effects against COVID-19 complications, but their role in reducing long COVID risk remains unclear.<br><br>METHODS: Utilizing the TriNetX platform, a retrospective cohort study was conducted among adults with type 2 diabetes diagnosed with COVID-19 between January 1, 2020, and June 30, 2024. Propensity score matching balanced demographic, clinical, and comorbidity profiles between SGLT2 inhibitor users and non-users. Cox proportional hazards regression assessed the risk of long COVID, defined by a spectrum of post-COVID-19 conditions.<br><br>RESULTS: Among 5,162 matched pairs, SGLT2 inhibitor use was associated with a significantly lower risk of long COVID (HR&#x2009;=&#x2009;0.85, 95% CI: 0.79-0.91). In the category of long-COVID symptoms such as abdominal symptoms, anxiety/depression, pain, headache, and cognitive symptoms, there were lower risks observed in the SGLT2 inhibitor group. Subgroup analyses showed consistent risk reduction across different age groups and sexes.<br><br>CONCLUSIONS: SGLT2 inhibitor use in patients with type 2 diabetes was linked to a reduced risk of long COVID. These findings suggest potential therapeutic benefits beyond glycemic control and highlight the need for further investigation into SGLT2 inhibitors as part of post-COVID-19 management strategies.},
}
@article {pmid41474983,
year = {2025},
author = {Zhang, TM and Sharp, SP and Scott, JD and Taren, D and Samaniego, JC and Unger, ER and Bertolli, J and Lin, JS and Ramers, CB and Godino, JG},
title = {Characterization of Post-Viral Infection Behaviors Among Patients With Long COVID: Prospective, Observational, Longitudinal Cohort Analyses of Fitbit Data and Patient-Reported Outcomes.},
journal = {JMIR formative research},
volume = {9},
number = {},
pages = {e77644},
pmid = {41474983},
issn = {2561-326X},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Exercise/physiology ; *Fatigue Syndrome, Chronic/physiopathology/psychology ; *Fitness Trackers ; Longitudinal Studies ; *Patient Reported Outcome Measures ; *Post-Acute COVID-19 Syndrome/physiopathology/psychology ; Prospective Studies ; SARS-CoV-2 ; Wearable Electronic Devices ; },
abstract = {BACKGROUND: Long COVID encompasses a range of health problems that can be highly debilitating. While some research has relied on self-reported measures of symptoms and functioning, few studies have characterized symptoms in relation to behaviors and physiology measured objectively through wearable devices.<br><br>OBJECTIVE: The primary aim of this study was to identify longitudinal patterns in physical activity, physiology, and patient-reported outcomes (PROs) among patients with long COVID at a Federally Qualified Health Center in the United States. The secondary aim was to identify meaningful subgroups or phenotypes within this cohort and examine how PROs and symptoms overlay with physical activity characteristics.<br><br>METHODS: This was a prospective, observational, longitudinal cohort study recruiting a subset of low-income patients enrolled in the Long COVID and Fatiguing Illness Recovery Program. From March 2022 to May 2023, a total of 172 patients with long COVID or myalgic encephalomyelitis/chronic fatigue syndrome were given Fitbit Charge 5 (Fitbit Inc) devices and instructed to wear them continuously for up to a year. Patients completed PRO questionnaires (PROMIS-29 [Patient-Reported Outcomes Measurement Information System-29] and symptom questionnaires, etc) at baseline, 3, and 6 months. Inclusion in longitudinal analysis required at least 20 hours of valid wear data per day for a minimum of 7 days. The World Health Organization guideline on moderate to vigorous physical activity (MVPA) was used to differentiate MPVA-active and MVPA-inactive patients. Linear mixed effects regression was performed to assess longitudinal associations between physical activity levels and PROs.<br><br>RESULTS: Among 172 patients, 80.2% (n=138) were female, 75.6% (n=130) were White, 45.3% (n=78) were unemployed, and 94.8% (n=163) had estimated annual income below US $50,000. Of these patients, 82 (47.7%) met valid wear criteria, providing 50.5 days of Fitbit data on average. At baseline, MVPA-inactive patients (n=41) reported statistically more severe problems regarding physical function, fatigue, and dyspnea than MVPA-active patients (n=41) on both continuous and categorical scales, with P<.05 from both Student t tests (2-tailed) and chi-squared tests. Longitudinal analysis found that MVPA-inactive patients showed a decreased ability to participate in social roles (estimated group difference=-4.21 T-score points over 3 months, 95% CI -6.64 to -1.78, P<.001) and a higher intensity of sleep symptoms (estimated group difference=2.06 severity score points over 3 months, 95% CI 0.40 to 3.71, P=.02) over time.<br><br>CONCLUSIONS: This study showed that patients with long COVID could remain MVPA-active despite experiencing symptoms. These findings provide insights into the relationship between PROs, physical activity, and long COVID, which suggests the importance of considering individual activity profiles when tailoring treatment plans, especially in a low-income population. The findings of this study should be interpreted as hypothesis-generating, considering its exploratory nature and limitations, including high attrition rates and missing data.},
}
@article {pmid41474066,
year = {2026},
author = {Vitiello, A},
title = {Long Covid Syndrome and Role of Autonomic Nervous System.},
journal = {Reviews in medical virology},
volume = {36},
number = {1},
pages = {e70101},
doi = {10.1002/rmv.70101},
pmid = {41474066},
issn = {1099-1654},
}
@article {pmid41472279,
year = {2025},
author = {Strumiliene, E and Malinauskiene, L and Urboniene, J and Jurgauskienė, L and Zablockienė, B and Jancoriene, L},
title = {Clinical and Immunological Recovery Trajectories in Severe COVID-19 Survivors: A 12-Month Prospective Follow-Up Study.},
journal = {Viruses},
volume = {17},
number = {12},
pages = {},
pmid = {41472279},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/immunology ; Male ; Female ; Middle Aged ; Prospective Studies ; Follow-Up Studies ; Adult ; SARS-CoV-2/immunology ; Aged ; Survivors ; Fatigue ; Killer Cells, Natural/immunology ; Lymphocyte Subsets/immunology ; Dyspnea ; Immunoglobulins/blood ; },
abstract = {Background: The link between clinical recovery and immune restoration after severe COVID-19 remains poorly defined. Although most survivors experience symptomatic improvement, persistent symptoms have been hypothesized to reflect ongoing immune dysregulation. Methods: This prospective cohort study followed 93 unvaccinated adults with RT-PCR-confirmed moderate-to-critical COVID-19 at 3, 6, and 12 months post-discharge. Clinical assessments used structured interviews to evaluate the persistent symptoms. Peripheral blood analyses were used to measure lymphocyte subsets, immunoglobulins, and complement components. Results: Clinical recovery was substantial; fatigue prevalence declined from 70.9% to 24.7% and dyspnea prevalence from 81.7% to 25.8% by 12 months (p < 0.001 for both). However, immune recovery exhibited divergent patterns. Activated T cells (CD3[+]HLA-DR[+]) decreased significantly (from 20% to 13%; p < 0.001), complement C3c levels paradoxically increased from 1.23 to 1.35 g/L (p < 0.001), and serum IgA increased by 32% (p = 0.003). NK cells remained stable overall but were persistently reduced in a subset (~25%) of patients, particularly among those with fatigue and dyspnea. Critical illness was associated with slower T-cell resolution, prolonged IgM elevation, and increased complement activity. Conclusions: One year after hospitalization, most patients achieved substantial clinical improvement, but immune reconstitution lagged behind. These findings highlight the dissociation between clinical and immunological recovery and suggest that persistent immune dysregulation may be associated with long COVID manifestations. Incorporating immune monitoring into post-COVID care may help identify patients at risk of prolonged sequelae and guide targeted therapeutic strategies.},
}
@article {pmid41472222,
year = {2025},
author = {Bhargava, A and Patel, H and Szpunar, S and Sharma, M and Somero, M and Moudgil, S and Saravolatz, L},
title = {Fatigue Severity, Cognitive Strain, and Psychological Health in Long COVID: Untangling the Interconnected Aftermath from a Dedicated Long COVID Clinic.},
journal = {Viruses},
volume = {17},
number = {12},
pages = {},
pmid = {41472222},
issn = {1999-4915},
support = {Medical staff funds//Henry Ford Hospital/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Cognitive Dysfunction/etiology/psychology ; Depression/etiology ; *Fatigue/diagnosis/etiology/psychology ; *Mental Health ; *Post-Acute COVID-19 Syndrome/complications/psychology ; Prospective Studies ; SARS-CoV-2 ; Severity of Illness Index ; Surveys and Questionnaires ; },
abstract = {Post-acute sequelae of SARS-CoV-2 infection (PASC) frequently includes persistent fatigue and cognitive dysfunction, but the relationship between these symptoms remains poorly defined. In this prospective observational study at the Henry Ford St. John Long COVID Clinic (LCC) from July 2023 to March 2025, we assessed fatigue severity using the Fatigue Assessment Scale (FAS) and examined its relationship with depression and cognitive symptoms. New patients completed demographic and clinical questionnaires, Patient Health Questionnaire (PHQ)-9, and Montreal Cognitive Assessment (MoCA) at their first LCC visit. Among 41 patients, 35 (85.4%) met the inclusion criteria for fatigue (FAS ≥ 22), with 18 (51.5%) experiencing severe fatigue (FAS > 34). Severe fatigue was significantly associated with shortness of breath, chest pain, and depression. Patients experiencing severe fatigue had significantly higher median PHQ-9 scores (12.5) compared to those with mild to moderate fatigue (5.0, p < 0.001). However, there were no significant differences in MoCA scores between these groups. Our study suggests a strong relationship between fatigue and depression in patients with PASC, emphasizing the importance of integrated physical and psychological healthcare. Moreover, since cognitive performance does not vary with fatigue levels, all PASC patients with cognitive dysfunction should receive routine cognitive screenings, regardless of the severity of their fatigue.},
}
@article {pmid41470215,
year = {2025},
author = {Macej, M and Grus, C and Čuj, J and Demjanovič Kendrová, L and Mikuľaková, WB and Kubincová, A and Takáč, P},
title = {Quality of Life and Functional Status in Individuals with Persistent Post-COVID Symptoms: A Cross-Sectional Comparison by Reported Rehabilitation.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {12},
pages = {},
pmid = {41470215},
issn = {1648-9144},
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Quality of Life/psychology ; *COVID-19/rehabilitation/complications/psychology ; Adult ; Middle Aged ; *Functional Status ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {Background and Objectives: Post-COVID-19 condition (PCC, long COVID) is associated with persistent symptoms and marked reductions in health-related quality of life (HRQoL), but real-world data on rehabilitation and everyday functioning remain limited. Materials and Methods: In a cross-sectional online survey conducted between 15 April and 15 May 2024, we analysed 406 adults (308 women; mean age 36.0 ± 12.1 years) with ongoing post-COVID symptoms recruited from two moderator-supervised support communities. The questionnaire included sociodemographic and clinical items, the 36-Item Short Form Health Survey (SF-36) and the Post-COVID-19 Functional Status (PCFS) scale. Participants indicated whether they had completed any form of rehabilitation targeting post-COVID problems (yes/no). Group differences were examined using Welch's t-test, Mann-Whitney U and χ[2] tests, as appropriate. Multiple linear regression models with Bonferroni correction were used to explore associations between rehabilitation status, age, sex, symptom duration and outcomes. Results: Overall, 182 respondents (44.8%) reported rehabilitation and 224 (55.2%) did not. The groups did not differ significantly in age, sex distribution, BMI, number of infections, symptom duration or hospitalisation history. Most SF-36 domains, component summaries and PCFS differed significantly between groups, with small-to-large effects favouring respondents who reported rehabilitation. The largest effect sizes were observed for Vitality and Mental Health, whereas Physical Functioning showed no clear difference. In multivariable models, older age and longer symptom duration were consistently associated with poorer HRQoL, while rehabilitation status remained a robust correlate of better scores in several SF-36 domains, both component summaries, perceived health, and lower PCFS grades after correction for multiple testing. Conclusions: Although the cross-sectional design, self-reported data and non-standardised rehabilitation exposure preclude causal inference, the findings highlight the substantial HRQoL and functional burden of long COVID and suggest that, within a symptomatic population, reported completion of rehabilitation is positively associated with multiple aspects of everyday health and functioning.},
}
@article {pmid41470138,
year = {2025},
author = {Septiana, M and Kaswandani, N and Yuniar, I and Iskandar, ATP and Puspitasari, HA and Satari, HI},
title = {Pulmonary Function and Associated Prognostic Factors in Children After COVID-19: A Retrospective Cohort Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {12},
pages = {},
pmid = {41470138},
issn = {1648-9144},
mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Comorbidity ; *COVID-19/physiopathology/complications/epidemiology ; *Lung/physiopathology ; Prevalence ; Prognosis ; Respiratory Function Tests ; Retrospective Studies ; Spirometry ; },
abstract = {Background and Objectives: Reports of respiratory function in COVID-19 survivors are still rare, especially in children. This study aims to determine the prevalence and prognostic factors that influence long-term respiratory function in children after COVID-19. Materials and Methods: An observational analytical study with a retrospective cohort design was conducted between January and June 2024. The subjects were pediatric patients aged 5-18 years with confirmed history of COVID-19. Respiratory function was evaluated with spirometry. The analyzed prognostic factors included clinical classification of COVID-19, gender, age, comorbidities, history of ventilator support, history of hospitalization and persistent symptoms. Results: A total of 100 subjects were included in this study. The subjects were 53% female, 52% aged ≥ 12-18 years, and 76% had at least one comorbidity, the most common being obesity (27%). The majority (73%) had a history of mild COVID-19, and 78% were not hospitalized. The prevalence of impaired lung function was 47%, dominated by restrictive lung pattern. The prevalence of long COVID was 18%, with the most common symptom being fatigue (13%). The presence of persistent symptom is significantly associated with abnormal spirometry result (p = 0.03, RR 1.99; 95% CI 1.38-2.87). Undernourished status and moderate-to-severe and critical COVID-19 significantly influence long-term respiratory function with p = 0.002, aOR 5.64; CI 95% 1.89-16.85 and p = 0.006, aOR 5.18; and CI 95% 1.59-16.89, respectively. Conclusions: The prevalence of impaired lung function in children after COVID-19 was 47%. Persistent symptoms, undernourished status, and moderate-to-critical severity of COVID-19 were found to be associated with impaired long-term respiratory function in post-COVID-19 pediatric patients. Further prospective studies are needed to confirm these findings and clarify causal mechanisms.},
}
@article {pmid41469619,
year = {2025},
author = {Braig, S and Peter, RS and Nieters, A and Kräusslich, HG and Brockmann, SO and Göpel, S and Merle, U and Steinacker, JM and Kern, WV and Rothenbacher, D and , },
title = {Post-Covid-19 symptoms, subjective work ability and sick leave 2 years after acute infection-results from a population-based long COVID study.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {354},
pmid = {41469619},
issn = {1471-2458},
mesh = {Humans ; *Sick Leave/statistics &amp; numerical data ; *COVID-19/complications/epidemiology/psychology ; Adult ; Middle Aged ; Male ; Female ; Germany/epidemiology ; Longitudinal Studies ; Young Adult ; Adolescent ; Aged ; Post-Acute COVID-19 Syndrome ; Return to Work/statistics &amp; numerical data ; *Work Capacity Evaluation ; Risk Factors ; SARS-CoV-2 ; },
abstract = {BACKGROUND: The post-COVID syndrome (PCS) is associated with reduced work ability, increased sick leave and delayed return to work. Yet, the relationship is complex due to a heterogeneous set of PCS symptoms and the multifaceted nature of work ability.<br><br>METHODS: Based on a population-based longitudinal study (n&#x2009;=&#x2009;5422, 18-65 years) conducted in the Southwest of Germany, we describe the evolution of work ability (mWAI1), task-related work ability (mWAI2), and sick leave 6-12 and 24 months after a SARS-CoV-2 index infection and confirmed by Polymerase Chain Reaction. Descriptive analyses on mWAI1 and mWAI2 and adjusted linear regression analyses were performed.<br><br>RESULTS: 1.1% of our population was continuously on sick leave since the initial SARS-CoV-2 infection (about 24 months after the infection). Pre-infection mWAI1 was not regained due to persisting or newly occurring symptoms of fatigue, neurocognitive impairment and anxiety/depression/sleep disorders that were related also to lower mWAI2. Effect modifiers of the associations between risk factors and mWAI1 or mWAI2 were age, working tasks, and comorbid mental conditions. Further SARS-CoV-2 infections were associated with poorer mWAI2 in physically (regression coefficient, 95% confidence intervals: -3.45 (-6.15,-0.74) but not mentally working participants (0.20 (-0.54,0.95)) and age proved to be a stronger risk factor for mWAI2 in physically working subjects.<br><br>CONCLUSIONS: We confirmed known risk factors but further emphasized effect modifiers like working task or comorbid mental disorders for work ability and described variables related to sick leave after SARS-CoV-2 infection.},
}
@article {pmid41467074,
year = {2025},
author = {Hendrickson, RC and Cheah, CS and Tai, ML and Pagulayan, KF and Liang, KJ and McCall, CA and Schindler, AG and Hart, KL and Rosser, AF and Oakley, JC},
title = {Impact of Prior History of Traumatic Stress on Autonomic and Multi-System Symptoms Following COVID-19 Infection.},
journal = {Chronic stress (Thousand Oaks, Calif.)},
volume = {9},
number = {},
pages = {24705470251407210},
pmid = {41467074},
issn = {2470-5470},
abstract = {BACKGROUND: Persistent symptoms of autonomic dysregulation are common after COVID-19 infection and may result from alterations in central and/or peripheral autonomic regulatory processes. Traumatic stress can cause persistent alterations in autonomic function, potentially changing the response to future traumatic or physiologic stressors. However, the relationship between prior history of traumatic stress and autonomic symptom burden after COVID-19 infection has not been explored.<br><br>OBJECTIVES: Examine the potential for additive and/or interactive effects of traumatic stress and COVID-19 infection on autonomic symptom burden, and compare this with other common post-acute sequelae of COVID-19 (PASC) symptom domains.<br><br>DESIGN: Observational, self-report, single time-point online assessment.<br><br>PARTICIPANTS: 404 United States adults with (N&#x2009;=&#x2009;289) and without (N&#x2009;=&#x2009;112) a self-reported history of COVID-19 infection.<br><br>MAIN OUTCOMES AND MEASURES: Autonomic symptom burden (Composite Autonomic Symptom Score [COMPASS 31]), lifetime traumatic stressors (Life Events Checklist), posttraumatic stress disorder (PTSD Checklist-5), self-reported neurocognitive functioning (Neuro-QoL), insomnia (Insomnia Severity Index), and fatigue and pain (PROMIS Fatigue and Pain Interference measures).<br><br>RESULTS: Autonomic symptom burden was significantly and positively related to both history of COVID-19 infection and number of probable lifetime traumatic stressors, with probable lifetime traumatic stressors functioning as a positive moderator of the relationship between history of COVID-19 infection and autonomic symptom burden (Cohen's partial f[2&#x2009;]=&#x2009;.11, .07 and .02 for COVID history, trauma history and interaction term respectively, all p&#x2009;<&#x2009;.05, in a model also including age and gender). The moderation effect remained significant when adjusting for both current PTSD symptoms and pre-existing multi-system PASC-like symptoms prior to COVID-19. History of traumatic stress and of COVID-19 infection each had significant and positive associations with other PASC symptom domains, but with domain-specific patterns.<br><br>CONCLUSIONS AND RELEVANCE: Prior history of traumatic stress has a positive and interactive effect on symptoms of autonomic dysregulation following COVID-19 infection, independent of PTSD symptoms. This suggests that exposure to traumatic stress may affect the response to future stressors, including physiologic stressors such as COVID-19 infection, through persistent changes in stress-threat response systems. This relationship may provide a physiologic explanation for prior observations that baseline anxiety prior to COVID-19 infection is associated with increased likelihood of PASC.},
}
@article {pmid41466718,
year = {2025},
author = {Kenny, TA},
title = {Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.},
journal = {Therapeutic advances in drug safety},
volume = {16},
number = {},
pages = {20420986251395925},
pmid = {41466718},
issn = {2042-0986},
abstract = {The COVID-19 pandemic has renewed attention to complex chronic health conditions that challenge conventional biomedical paradigms. Syndromes such as postural orthostatic tachycardia syndrome and myalgic encephalomyelitis/chronic fatigue syndrome have gained broader visibility through the lens of Long COVID. As global vaccination campaigns expanded, a subset of individuals began reporting similarly persistent, multisystem symptoms following COVID-19 immunization-informally referred to as post-COVID-19 vaccination syndrome. These presentations, which include dysautonomia, neuropathic pain, post-exertional malaise, and cognitive dysfunction, resemble post-infectious syndromes and may involve shared immune-related mechanisms. Although no causal relationship to vaccination has been established, these cases-together with comparable reports following other vaccines-highlight limitations in current vaccine safety systems for detecting and evaluating complex chronic outcomes. This article introduces the concept of complex chronic adverse events following immunization (CC-AEFIs) as a pragmatic, surveillance-oriented framework to support the systematic identification and investigation of such cases. CC-AEFIs are not syndromic diagnoses but a higher-order category encompassing persistent, multifactorial conditions that may follow immunization yet challenge existing pharmacovigilance definitions and tools. These conditions often involve multiple organ systems, delayed onset, fluctuating trajectories, diagnostic ambiguity, and symptom heterogeneity. Drawing on the author's lived experience as an affected patient and integrating clinical, regulatory, and experiential evidence, the analysis examines structural and epistemic limitations across the pharmacovigilance continuum-from underrecognition in clinical settings to analytic exclusion and constrained governance. It concludes by proposing reforms to strengthen safety-system responsiveness, including enhanced diagnostic training, longitudinal surveillance, patient-reported outcome integration, and analytic transparency. Addressing these limitations is essential to sustain public trust, ensure equitable care, and uphold the scientific integrity of immunization programs.},
}
@article {pmid41466608,
year = {2025},
author = {de Bruijn, S and Huiberts, AJ and Andeweg, SP and Hoeve, CE and Schipper, M and Grobbee, DE and de Melker, HE and van de Wijgert, JHHM and van den Hof, S and Knol, MJ and van den Wijngaard, CC},
title = {Post-COVID-19 condition in individuals infected with SARS-CoV-2 in autumn 2023 in the Netherlands: a prospective cohort study with pre- and post-infection data.},
journal = {The Lancet regional health. Europe},
volume = {59},
number = {},
pages = {101472},
pmid = {41466608},
issn = {2666-7762},
abstract = {BACKGROUND: Post-COVID-19 condition (PCC) risk may have changed due to vaccination status, virus variants, prior infections, and other factors. We aimed to estimate PCC prevalence for one year in individuals infected with SARS-CoV-2 during autumn 2023, controlling for pre-infection symptoms and prevalence in recently uninfected participants.<br><br>METHODS: VASCO, a Dutch ongoing prospective cohort, collects three-monthly questionnaires and six-monthly SARS-CoV-2 serology. Participants indicated severity of 23 symptoms on a five-point Likert scale, and of fatigue and concentration problems on the Checklist Individual Strength. We matched participants who did with those who did not report a SARS-CoV-2 infection between September 25, 2023 and January 7, 2024, and censored follow-up time for both upon serological or antigen test evidence of infection. We estimated PCC-prevalence as the excess prevalence of at least one PCC-related symptom between matched infected and uninfected participants at 90, 180, 270, and 360 days post-infection. Additionally, participants could self-attribute long-term symptoms to SARS-CoV-2.<br><br>FINDINGS: We 1:1 matched 5621 infected to 5621 uninfected participants. The PCC prevalence, estimated as the marginal mean excess prevalence of PCC-related symptoms between infected and uninfected participants, was 0.2% (95% confidence interval: -1.9 to 2.3, p = 0.84) at 90 days, 0.5% (-1.6 to 2.6, p = 0.63) at 180 days, 0.7% (-1.3 to 2.8, p = 0.48) at 270 days, and 0.0% (-2.1 to 2.1, p = 0.99) at 360 days. Excess prevalence of new mild and severe long-term symptoms self-attributed to SARS-CoV-2 between infected and uninfected participants were both elevated at 90 days (mild: 7.2% (5.1-9.2), severe: 0.6% (0.4-0.8)) and 180 days (mild: 3.2% (2.0-4.4), severe: 0.3% (0.2-0.4)) post-infection (all p-values <0.0001), but no longer thereafter.<br><br>INTERPRETATION: This double-controlled study, incorporating pre- versus post-infection and uninfected symptom data, found a low risk of PCC among a community-dwelling adult population infected during the autumn 2023 SARS-CoV-2 wave. The prevalence of PCC-related symptoms in infected and uninfected individuals was not significantly different at 90-360 days post-infection. The excess prevalences of self-attributed long-term symptoms were elevated at 90 and 180 days post-infection but no longer from 270 days onwards. These findings suggest that the 2023 wave inferred a lower PCC risk than during the pandemic period.<br><br>FUNDING: Funded by the Dutch Ministry of Health, Welfare and Sport.},
}
@article {pmid41465566,
year = {2025},
author = {Khodanovich, M and Kamaeva, D and Usova, A and Pashkevich, V and Moshkina, M and Obukhovskaya, V and Kataeva, N and Levina, A and Tumentceva, Y and Shadrina, M and Ranzaeva, A and Vasilieva, S and Schastnyy, E and Naumova, A and Svetlik, M},
title = {Demyelination and Cognitive Performance in Long COVID Patients with Insomnia and/or Depression.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
pmid = {41465566},
issn = {1422-0067},
support = {22-15-00481-&#x41f;//Russian Science Foundation/ ; },
mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/complications/etiology ; Male ; Female ; *COVID-19/complications/psychology ; Middle Aged ; *Depression/complications/etiology ; *Demyelinating Diseases/etiology/diagnostic imaging ; Magnetic Resonance Imaging ; Adult ; *Cognition ; SARS-CoV-2 ; Biomarkers/blood ; *Cognitive Dysfunction/etiology ; Case-Control Studies ; Neuropsychological Tests ; White Matter/diagnostic imaging/pathology ; Aged ; },
abstract = {Insomnia and depression are severe sequelae of COVID-19 and often occur simultaneously. Our study examined associations of insomnia and/or depression with cognitive impairments, white matter changes, and serum biomarkers. In total, 76 long COVID patients and 22 healthy controls were examined using neuropsychiatric (ISI, HADS, and HDRS) and cognitive (MoCA, Stroop, WMT, and TMT) tests, with their blood biomarkers (anti-SARS-CoV-2, BDNF, anti-S100, anti-MBP, and anti-PLP) investigated, and underwent MRI using macromolecular proton fraction (MPF) mapping to quantify myelination. The Insomnia (n = 14), Depression (n = 12), InsDep (comorbid insomnia-depression, n = 13), and PostCovid (long COVID without depression and insomnia, n = 32) groups were identified based on psychiatric/neurological diagnoses and neuropsychiatric assessment. Cognitive performance was most affected in the Insomnia group in the MoCA and CW Stroop tests. The Depression group underperformed in the TMT and W Stroop task; the InsDep group underperformed in the WMT. The Insomnia group showed the greatest demyelination, affecting commissural (CC and tapetum), projection (CR, IC, CST, cerebral peduncles, CP, and ML), and some association pathways (SLF, SFOF), as well as most juxtacortical regions, the thalamus, and the midbrain; these changes correlated with insomnia severity. The Depression and InsDep groups showed smaller but significant overall demyelination correlated with depression severity. The Depression group exhibited the highest MPF decrease in the globus pallidus, putamen, and external capsule, while the InsDep group demonstrated the highest demyelination of the association pathways IFOF, UF, and cingulum. The anti-PLP levels were the highest in the Insomnia group and correlated with both the persistence of insomnia/depression symptoms and demyelination. Demyelination in long COVID is associated with high levels of myelin-specific autoantibodies, but symptoms of insomnia and/or depression are associated with demyelination of a different set of brain structures.},
}
@article {pmid41464688,
year = {2025},
author = {Miana, M and Moreta-Fuentes, C and Moreta-Fuentes, R and Varillas-Delgado, D and Jiménez-Antona, C and Laguarta-Val, S},
title = {Clinical Improvements Following a Non-Aerobic Therapeutic Exercise in Women with Long COVID.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
pmid = {41464688},
issn = {2077-0383},
abstract = {Background/Objectives: Long COVID (LC) is characterized by persistent symptoms such as fatigue, pain, and reduced quality of life, often lasting months after acute infection. Exercise-based interventions have shown promise, but evidence for non-aerobic programs remains limited. This study aimed to evaluate the effects of a 12-week motor control exercise program on body composition and fatigue in women with LC and to explore associations with physical activity and psychosocial factors. Methods: An exploratory pre-post non-controlled intervention study was conducted in 17 women with LC symptoms persisting for over one year. Participants completed 24 individualized sessions of a non-aerobic therapeutic exercise program focused on trunk stabilization. Outcomes included body composition (bioimpedance analysis), fatigue (Modified Fatigue Impact Scale), health-related quality of life (EQ-5D-5L), physical activity (IPAQ), and kinesiophobia (TSK-11). Paired t-tests, effect sizes, correlations, and regression models were applied. Results: The intervention significantly reduced total body fat (37.09% to 35.41%, p < 0.001) and trunk fat (35.82% to 33.82%, p < 0.001), with large effect sizes. Physical and psychosocial fatigue improved markedly (MFIS physical: 29.71 to 21.06, p < 0.001; psychosocial: 6.00 to 4.29, p = 0.001), while cognitive fatigue showed non-significant change. Pain/discomfort scores decreased substantially (2.86 to 1.79, p < 0.001). Vigorous activity and walking time increased, and sedentary time decreased. No significant changes were observed in muscle mass or kinesiophobia. Conclusions: A structured, non-aerobic exercise program can effectively reduce body fat, alleviate fatigue, and improve pain perception in women with LC, supporting its role in rehabilitation. Multimodal strategies may be required to address cognitive symptoms and fear of movement.},
}
@article {pmid41464319,
year = {2025},
author = {Raycheva, R and Kostadinov, K and Rangelova, V and Kevorkyan, A},
title = {Economic Analyses of COVID-19 Interventions: A Narrative Review of Global Evidence.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {24},
pages = {},
pmid = {41464319},
issn = {2227-9032},
abstract = {Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic imposed an unprecedented global health and economic burden, prompting rapid implementation of diverse public health interventions. This review aimed to synthesize global evidence on the cost-effectiveness of key COVID-19 control strategies, including vaccination, testing, and social distancing and to identify methodological, contextual, and equity-related determinants of their economic value. Methods: A narrative literature review was conducted using peer-reviewed studies published between January 2020 and September 2025 and indexed in PubMed, Scopus, and Web of Science. Eligible studies included economic evaluations and modeling analyses addressing COVID-19 interventions in healthcare, community, or educational settings. Data on costs, outcomes, and methodological features were extracted and synthesized descriptively. Results: Across 74 included studies, vaccination-particularly with messenger RNA (mRNA) platforms-emerged as the most cost-effective intervention across all settings, often cost-saving among high-risk populations. Combined or layered strategies integrating vaccination, testing, and selective social distancing consistently outperformed single interventions in both health and economic outcomes. Early and targeted implementation yielded the highest cost-effectiveness by preventing exponential transmission and healthcare overload. However, heterogeneity in modeling assumptions, analytic perspectives, and outcome measures limited comparability. Few studies applied extended or distributional cost-effectiveness frameworks to address equity, while indirect and long-term effects such as productivity losses and "long COVID" were frequently omitted. Conclusions: COVID-19 interventions are most efficient when early, targeted, and adaptive to local epidemiologic conditions. Integrating equity, methodological consistency, and broader societal impacts into future evaluations will strengthen evidence-based, economically sustainable pandemic preparedness and response strategies.},
}
@article {pmid41463036,
year = {2025},
author = {Andriankaja, OM and Whiteheart, S and Mattos, MBA},
title = {Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
pmid = {41463036},
issn = {2227-9059},
abstract = {Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., "long-COVID," "post-acute sequelae of SARS-CoV-2 infection," "PASC," "post-COVID-19," "long-haul COVID") and oral/periodontal diseases (e.g., "periodontal disease," "periodontitis," "gingiva," "oral disease," "dental"), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein-Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships.},
}
@article {pmid41463013,
year = {2025},
author = {Petrov, S and Bozhkova, M and Ivanovska, M and Kalfova, T and Dudova, D and Nikolova, R and Vaseva, K and Todorova, Y and Aleksova, M and Nikolova, M and Taskov, H and Murdjeva, M and Maes, M},
title = {Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
pmid = {41463013},
issn = {2227-9059},
support = {BG-RRP-2.004-0007-C01//STRATEGIC RESEARCH AND INNOVATION PROGRAMME FOR THE DEVELOPMENT OF THE MEDICAL UNIVERSITY - PLOVDIV (SRIPD-MUP)/ ; },
abstract = {Background: Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and multisystemic symptoms, such as cognitive impairment, musculoskeletal pain, and post-exertional malaise. Recently, parallels have been drawn between ME/CFS and Long COVID, a post-viral syndrome following infection with SARS-CoV-2, which shares many clinical features with CFS. Both conditions involve chronic immune activation, raising questions about their immunopathological overlap. Objectives: This study aimed to compare immune biomarkers between patients with ME/CFS or Long COVID and healthy controls to explore shared immune dysfunction. Methods: We analyzed lymphocyte subsets, cytokine profiles, psychological status and their correlations in 190 participants, 65 with CFS, 54 with Long COVID, and 70 healthy controls. Results: When compared to healthy subjects, results in both conditions were marked by lower levels of lymphocytes (CFS-2.472 × 10[9]/L, p = 0.006, LC-2.051 × 10[9]/L, p = 0.009), CD8[+] T cells (CFS-0.394 × 10[9]/L, p = 0.001, LC-0.404 × 10[9]/L, p = 0.001), and NK cells (CFS-0.205 × 10[9]/L, p = 0.001, LC-0.180 × 10[9]/L, p = 0.001), and higher levels of proinflammatory cytokines such as IL-6 (CFS-3.35 pg/mL, p = 0.050 LC-4.04 pg/mL, p = 0.001), TNF (CFS-2.64 pg/mL, p = 0.023, LC-2.50 pg/mL, p = 0.025), IL-4 (CFS-3.72 pg/mL, p = 0.041, LC-3.45 pg/mL, p = 0.048), and IL-10 (CFS-2.29 pg/mL, p = 0.039, LC-2.25 pg/mL, p = 0.018). Conclusions: Notably, there were no significant differences between CFS and Long COVID patients in the tested biomarkers. These results demonstrate that ME/CFS and Long COVID display comparable immune and inflammatory profiles, with no significant biomarker differences observed between the two groups.},
}
@article {pmid41462874,
year = {2025},
author = {Halas, RG and Berceanu Vaduva, DM and Radulescu, M and Bredicean, AC and Mateescu, DM and Toma, AO and Cotet, IG and Guse, CE and Marginean, A and Margan, MM and Lazureanu, VE},
title = {Long COVID Prevalence and Risk Factors: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
pmid = {41462874},
issn = {2227-9059},
abstract = {Background: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects millions globally, with persistent symptoms impacting quality of life. This meta-analysis synthesizes prospective cohort studies to estimate the prevalence of Long COVID symptoms and identify risk factors. Methods: We systematically searched PubMed for prospective cohort studies (2020-2025) on Long COVID, focusing on prevalence and risk factors. Studies with ≥100 participants and follow-up ≥3 months were included. Data were extracted on symptom prevalence (e.g., fatigue, dyspnoea) and risk factors (e.g., sex, hospitalization). Random-effects models were used to pool prevalence and odds ratios (OR). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Results: Fourteen prospective studies (n = 168,679) were included. Pooled prevalence of Long COVID was 18.0% (95% CI: 12.5-23.5%, I[2] = 9.8%) among survivors followed for ≥6 months. Fatigue (41.0%, 95% CI: 33.2-49.4%) and dyspnoea (22.5%, 95% CI: 15.6-29.8%) were the most common symptoms. Female sex (OR = 1.52, 95% CI: 1.25-1.92) and prior hospitalization (OR = 2.35, 95% CI: 1.98-2.90) were significant risk factors. High heterogeneity (I[2] > 90%) was noted. Conclusions: Long COVID affects over one-fifth of SARS-CoV-2 survivors, with fatigue and dyspnoea persisting in many. Female sex and severe acute infection increase risk. Standardized definitions and longer follow-up are needed.},
}
@article {pmid41462744,
year = {2025},
author = {Fronticelli Baldelli, G and Buonsenso, D},
title = {Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.},
journal = {Children (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
pmid = {41462744},
issn = {2227-9067},
abstract = {Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood-brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes.},
}
@article {pmid41462476,
year = {2025},
author = {Tamim El Jarkass, T and Nandakumar, S and Skidmore, B and Pinto, AD and Hosseini, B},
title = {Understanding how social determinants of health shape Long COVID outcomes: a rapid review of evidence.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {308},
pmid = {41462476},
issn = {0778-7367},
support = {Grant #FRN 183092 and PPE 190332/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Long COVID affects over 65 million people worldwide, yet the impact of social determinants of health (SDoH), such as socioeconomic status, race/ethnicity, education, occupation, and geography, remains poorly understood. To evaluate the association between SDoH and the risk and severity of Long COVID.<br><br>METHODS: A rapid review of observational studies was conducted using MEDLINE, Embase, and Web of Science (up to September 29, 2024). Studies reporting original data on SDoH and Long COVID outcomes were included. Data were extracted on study characteristics, population demographics, Long COVID definitions, and SDoH-related findings. Study quality was assessed using the Newcastle-Ottawa Scale.<br><br>RESULTS: Seventy-one studies (43 cohort, 28 cross-sectional) were included. Definitions of Long COVID varied. Commonly studied SDoH included age, sex, race/ethnicity, education, financial security, employment, and geography. Female sex and older age were consistently associated with increased risk and severity of Long COVID. Black and Hispanic individuals were more likely to experience Long COVID. Lower education and financial insecurity were also linked to greater prevalence and symptom burden. Frontline and essential workers were found to be at increased risk. Geographic disparities were evident but varied across rural and urban residence.<br><br>CONCLUSIONS: SDoH play a key role in shaping Long COVID outcomes. Addressing these disparities requires targeted public health efforts and standardized case definitions.},
}
@article {pmid41461919,
year = {2025},
author = {Kim, S and D'Anniballe, VM and Finlay, JB and Ko, T and Wang, M and Jang, DW and Abi-Hachem, R and Goldstein, BJ},
title = {Analysis of mucosal immune dysregulation and safety and tolerability of endoscopic topical steroid therapy for long-COVID hyposmia: randomized, double-blinded pilot study.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {60},
pmid = {41461919},
issn = {2730-664X},
support = {R25 DC020172/DC/NIDCD NIH HHS/United States ; DC020172//U.S. Department of Health &amp; Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/ ; },
abstract = {BACKGROUND: Millions of people exhibit olfactory dysfunction years after acute SARS-CoV-2 infection. Evidence suggests unresolved olfactory epithelial inflammation may perturb function. Here, we report (1) data from human olfactory biopsies processed for T cell studies, and (2) outcomes from a pilot clinical trial evaluating endoscopic delivery of beclomethasone to the olfactory cleft for improving olfaction in long-COVID hyposmia.<br><br>METHODS: Biopsies from long-COVID hyposmia and control subjects underwent single-cell T-cell receptor (TCR) sequencing. In a separate outpatient cohort (Duke Rhinology Clinics), we conducted a randomized, double-blind, placebo-controlled pilot trial. Eligible adults (&#x2265;18&#x2009;y) had &#x2265;3 months long-COVID smell loss confirmed by Smell Identification Test (SIT). Participants were randomized 1:1 to endoscopic delivery of saline or beclomethasone via dissolvable sponge; repeated at 2 weeks. The primary outcome was SIT improvement &#x2265;4 points at 1 month; secondary at 3 months. Study recruitment ran Sept 15, 2023-June 18, 2024.<br><br>RESULTS: Biopsies show no evidence of SARS-CoV-2 or EBV/HHV-6 reactivation and demonstrate clonally expanded, pro-inflammatory T-cell subsets. Fifteen subjects are randomized (beclomethasone n&#x2009;=&#x2009;7, saline n&#x2009;=&#x2009;8); 13 are analyzed (6 and 7). At 1 month, SIT improvement occurs in 66.7% (4/6) vs 28.6% (2/7) (risk difference 38.1%, 95% CI 2-97%; risk ratio 2.14, 95% CI 0.73-7.79; p&#x2009;=&#x2009;0.28). At 3 months, rates are 66.7% vs 42.9% (RD 23.8%, 95% CI 17-80%; RR 1.74, 95% CI 0.52-6.5; p&#x2009;=&#x2009;0.50). No adverse events are reported.<br><br>CONCLUSIONS: Human olfactory TCR-seq implicates local T-cell inflammation without local viral reservoirs. Directed, endoscopic topical steroid therapy is feasible and safe, with a non-significant trend toward improved olfaction, supporting larger trials.<br><br>FUNDING: NIH DC020172, American Academy of Otolaryngology-Head and Neck Surgery.},
}
@article {pmid41459516,
year = {2025},
author = {de Jesus Silva, J and Horta, LS and Viana, SM and Cazé, AB and Oliveira, IS and Pereira, MM and Antas Nascimento, N and Pereira, BJ and Bonyek-Silva, &#xcd; and Nunes de Oliveira Araújo, S and de Marinho, AIL and Rocha Cristal, J and Rao, V and Coelho, C and Cerqueira-Silva, T and Malmegrim, KCR and Camelier, A and Cardoso, CRB and Tavares, NM and Barral-Netto, M and Barral, A and Barbosa, C and Boaventura, VS},
title = {Autoantibodies in long COVID in a black/mixed population compared with recovered and pre-pandemic controls.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1684482},
pmid = {41459516},
issn = {1664-3224},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Autoantibodies/blood/immunology ; Black People ; *COVID-19/immunology/blood/ethnology ; *Post-Acute COVID-19 Syndrome/blood/ethnology/immunology ; },
abstract = {INTRODUCTION: Long COVID (LC), a clinical condition marked by persistent and new symptoms after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects up to 10-20% of infected individuals. Although autoimmunity has been proposed as a key mechanism, the specific role of circulating autoantibodies in LC remains unclear. We characterized the autoantibody profiles in individuals with LC and assessed their association with persistent post-COVID symptoms, in comparison to recovered patients and pre-pandemic healthy controls (PPHC).<br><br>METHODS: We analyzed 17 autoantibodies in a cohort of 220 pre-pandemic controls and 291 COVID-19 patients, targeting self-antigens. Of those, 237 patients presented symptoms for a month or more after the onset of SARS-CoV-2 infection (long COVID patients), and 54 individuals recovered from the initial infection without chronic symptoms. Autoantibody frequencies and associations with clinical variables were assessed using logistic regression and subgroup analyses.<br><br>RESULTS: Autoantibody prevalence was higher in recovered individuals (37%) than in LC patients (24%) or PPHC (19%). While certain autoantibodies such as a-cardiolipin (a-CL) IgM, a-AML IgG, a-SSA IgG and a-SSB IgG were elevated in some COVID-19 patients, they were not significantly different in LC. The most frequently detected autoantibody was a-CL IgM, found across all groups and especially in individuals that fully recovered from COVID-19. However, a-CL did not differentiate individuals with long COVID or correlate with symptom persistence but was associated with the occurrence of dysphagia and anorexia as symptoms. No correlation was observed between autoantibody presence and disease severity.<br><br>DISCUSSION: These findings do not support a primary pathogenic role for the evaluated autoantibodies in LC and emphasize the need for longitudinal studies to explore their temporal dynamics and interaction with other immunological or clinical factors involved in post-COVID-19 conditions.},
}
@article {pmid41457787,
year = {2026},
author = {Igarashi, Y and Tateishi, S and Sawajima, T and Harada, A and Matsuoka, J and Kawasumi, M and Mori, K},
title = {Occupational physicians' practices in supporting employees with long COVID: a mixed-methods study.},
journal = {Journal of occupational health},
volume = {68},
number = {1},
pages = {},
pmid = {41457787},
issn = {1348-9585},
support = {//the University of Occupational and Environmental Health, Japan: Research Grant for Promotion of Occupational Health (R4-R5)/ ; },
abstract = {OBJECTIVES: This study examined the support provided by occupational physicians (OPs) in Japan to employees with long COVID, a condition that significantly affected workforce health during the pandemic.<br><br>METHODS: An exploratory cross-sectional mixed-methods design was employed, consisting of qualitative interviews followed by a questionnaire survey targeting OPs certified by the Japan Society for Occupational Health. The interviews explored actual experiences of supporting workers with long COVID, and the findings were used to develop the questionnaire. The survey and interview findings were integrated to describe overall occupational health (OH) practices.<br><br>RESULTS: Twenty OPs reported 30 cases of employees with long COVID in the interviews. Based on these findings, a questionnaire survey was conducted, yielding 182 valid responses. The integrated results showed that OPs most frequently reported "Main OH responses" such as active listening, return-to-work assistance, and lifestyle guidance. Measures such as explaining workers' compensation applications and preparing lists of outpatient clinics were less frequently reported. For "Advice for employers," limitation of overtime, reduction of workload, and telework were commonly reported, whereas demotion and reassignment were rarely reported.<br><br>CONCLUSIONS: This study clarified how OPs in Japan supported workers with long COVID through diverse, context-dependent practices. The identified main OH responses and advice for employers provide a framework for understanding current practices. Developing practical case examples, structured assessment tools, and workplace guidelines, together with further research grounded in real-world practice, will enhance OPs' ability to provide appropriate support and strengthen preparedness for future health crises.},
}
@article {pmid41457697,
year = {2026},
author = {Lin, LY and Chen, CJ and Chen, MH and Chen, CW and Chen, PC},
title = {The association between COVID-19 and incident gestational diabetes (GDM): A population-based case-control study of the National Health Insurance Research Database in Taiwan.},
journal = {Journal of diabetes investigation},
volume = {17},
number = {3},
pages = {527-534},
pmid = {41457697},
issn = {2040-1124},
support = {NTU-NFG-113L7463//National Taiwan University/ ; NTU-NFG-114L7406//National Taiwan University/ ; NHRI-EM-113-GP-03//National Health Research Institutes/ ; NHRI-EM-114-GP-03//National Health Research Institutes/ ; NSTC 113-2314-B-002-316-//National Science and Technology Council/ ; NSTC 114-2314-B-002-110-//National Science and Technology Council/ ; },
mesh = {Humans ; Female ; *Diabetes, Gestational/epidemiology/etiology ; Pregnancy ; Taiwan/epidemiology ; *COVID-19/epidemiology/complications ; Case-Control Studies ; Adult ; Databases, Factual ; Incidence ; SARS-CoV-2 ; National Health Programs/statistics &amp; numerical data ; Risk Factors ; Young Adult ; *Pregnancy Complications, Infectious/epidemiology ; },
abstract = {BACKGROUND: Reports suggested that diabetes could be a complication arising from COVID-19; however, the relationship between COVID-19 and the development of gestational diabetes mellitus (GDM) remains unclear.<br><br>OBJECTIVES: This study aimed to investigate the association between COVID-19 infections and the risk of incident GDM in pregnant women.<br><br>METHODS: We analyzed data from Taiwan's National Health Insurance Research Database (NHIRD), which is linked to the Birth Reporting Database and the COVID-19 testing database between 2020 and 2022. A case-control study was conducted, matching pregnant women by age and region. We employed multivariable logistic regression, adjusting for matching factors and potential confounders. The findings were further validated through a sensitivity analysis using a cohort design with landmark analysis.<br><br>RESULTS: The study included 134,375 pregnant women, comprising 26,875 GDM cases and 107,500 matched controls. After adjusting for covariates, we found no evidence supporting an association between prior COVID-19 infection and incident GDM (adjusted odds ratio [aOR]&#x2009;=&#x2009;0.95, 95% confidence interval [CI]&#x2009;=&#x2009;0.89-1.01). Notably, some evidence showed that receiving at least one COVID-19 vaccination was associated with a decreased risk of GDM (aOR&#x2009;=&#x2009;0.90, 95% CI&#x2009;=&#x2009;0.87-0.93). These results remained consistent in the sensitivity analysis.<br><br>CONCLUSION: Despite COVID-19 now being endemic with less virulent variants, ongoing vigilance regarding potential pregnancy-related impacts of SARS-CoV-2 is essential. It is also critical to promote vaccination among women of childbearing age, and further research is necessary to explore COVID-19-related complications during pregnancy.},
}
@article {pmid41457003,
year = {2025},
author = {Plaut, S},
title = {Correspondence on 'Rheumatology and Long COVID: lessons from the study of fibromyalgia?' by Clauw and Calabrese.},
journal = {Annals of the rheumatic diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ard.2025.12.001},
pmid = {41457003},
issn = {1468-2060},
}
@article {pmid41455934,
year = {2025},
author = {Sisti, JS and Packard, SE and Metzler, J},
title = {Long COVID symptoms and loneliness: findings from the World Trade Center Health Registry.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {392},
pmid = {41455934},
issn = {1471-2458},
support = {U47 OE000057/OE/OSELS CDC HHS/United States ; U50 OH009739/OH/NIOSH CDC HHS/United States ; NE11OE000057/CC/CDC HHS/United States ; U50OH009739/OH/NIOSH CDC HHS/United States ; },
mesh = {Humans ; *Loneliness/psychology ; *COVID-19/psychology/epidemiology ; Male ; Female ; Registries ; Middle Aged ; Adult ; Aged ; Social Support ; *September 11 Terrorist Attacks/psychology ; New York City/epidemiology ; Prevalence ; },
abstract = {BACKGROUND: Symptoms of long COVID can profoundly impact affected individuals' functioning, including their ability to participate in social activities. While individuals experiencing long COVID symptoms frequently report loneliness, few studies to date have investigated whether loneliness is more common among those with symptoms compared to those without. We examined associations between long COVID symptoms and loneliness among World Trade Center Health Registry (WTCHR) enrollees.<br><br>METHODS: Among WTCHR enrollees who reported an acute COVID-19 infection in 2022-23 on a self-administered survey, we used modified Poisson regression to estimate multivariable-adjusted prevalence ratios (PR) and 95% confidence intervals (95% CI) for associations of self-reported long COVID symptoms (any vs. none, selected from a predefined symptom list) with loneliness. Overall loneliness was assessed with the 6-item de Jong Gierveld loneliness scale (range: 0-6); social and emotional loneliness were assessed with their respective subscales (range: 0-3). We also assessed whether level of social support prior to COVID-19 infection modified associations of long COVID symptoms with loneliness.<br><br>RESULTS: Analyses included 5,692 enrollees (mean age: 62 years); prevalence of loneliness was 61%. In fully adjusted models, enrollees who reported any long COVID symptoms had higher prevalence of loneliness compared to those without symptoms (PR&#x2009;=&#x2009;1.19, 95% CI:1.13, 1.25). Associations were somewhat stronger for emotional loneliness than for social loneliness (PR&#x2009;=&#x2009;1.22, 95% CI:1.15, 1.29 and PR&#x2009;=&#x2009;1.12, 95% CI:1.07, 1.18, respectively). Effect modification by social support was not observed on either the additive or multiplicative scale.<br><br>CONCLUSION: Long COVID symptoms were associated with prevalence of loneliness in a sample of primarily older adults. As loneliness itself is associated with subsequent adverse health outcomes, addressing loneliness among people living with long COVID may help prevent further reductions in quality of life.},
}
@article {pmid41447955,
year = {2026},
author = {Talamini, L and Verdot, C and Shoenfeld, Y and Muller, S},
title = {Pathophysiological effects of long COVID-19 (auto)antibodies on fertility.},
journal = {Journal of autoimmunity},
volume = {158},
number = {},
pages = {103518},
doi = {10.1016/j.jaut.2025.103518},
pmid = {41447955},
issn = {1095-9157},
mesh = {Animals ; *COVID-19/immunology ; Female ; *SARS-CoV-2/immunology ; Mice ; Male ; *Autoantibodies/immunology ; Humans ; *Fertility/immunology ; *Spike Glycoprotein, Coronavirus/immunology ; Molecular Mimicry/immunology ; Cross Reactions/immunology ; *Antibodies, Viral/immunology ; Autoantigens/immunology ; Autoimmunity ; },
abstract = {Molecular mimicry between foreign and self-antigens has long been recognized to initiate/exacerbate autoimmunity. Shared amino acid sequences have been found between SARS-CoV-2 Spike glycoprotein and human self-proteins, raising concerns about potential damages. We previously identified sequences with ≥5 identical residues shared by the SARS-CoV-2 Spike and spermatogenesis-associated proteins. One of these peptides was especially recognized by antibodies from infected, but not vaccinated individuals. Here, their pathogenic effects were explored in vivo. Injection of peptide antibodies into healthy male mice impaired fertility or delayed delivery time in fertile females, suggesting that cross-reactivity via molecular mimicry might affect the human reproductive system.},
}
@article {pmid41445780,
year = {2025},
author = {N, SR and Jin, GW and Choy, JH},
title = {Translational potential of safe-by-design nanoengineered niclosamide in viral and cancer therapy.},
journal = {Materials today. Bio},
volume = {35},
number = {},
pages = {102610},
pmid = {41445780},
issn = {2590-0064},
abstract = {This study presents a comprehensive evaluation of the long-term biocompatibility of CP-COV03 (NIC-MgO-HPMC), a nanohybrid formulation of niclosamide designed to overcome its limitations in solubility, stability, and bioavailability. Developed under a safe-by-design framework, NIC-MgO-HPMC integrates magnesium oxide (MgO) nanoparticles with hydroxypropyl methylcellulose (HPMC) to enhance pharmacological performance while ensuring safety for chronic use. Over a 13-week in vivo exposure period, the toxicological profile was systematically assessed, focusing on hepatic, renal, and hematologic systems. Clinical observations, serum biochemistry, and hematology revealed no abnormalities at clinically relevant dosages. Histopathological examination of major organs confirmed the absence of tissue damage or structural alterations, underscoring the nanohybrid's long-term tolerability. These findings establish the first foundational safety benchmark for chronic use of nanoengineered niclosamide hybrids. The absence of systemic toxicities validates CP-COV03 as a scalable and biocompatible therapeutic platform suitable for extended dosing regimens. By combining durable safety with enhanced drug performance, CP-COV03 offers strong translational potential for persistent viral infections, including long COVID, future pandemic threats, and oncology applications.},
}
@article {pmid41445680,
year = {2025},
author = {Tura, NC and da Silva Pereira, F and Fogaça, B and Pang, AS and do Amaral, LA and Barbosa, RI},
title = {Efficacy of Synchronous vs. Asynchronous Telerehabilitation for Musculoskeletal Symptoms in Post-Covid-19 Syndrome: A Randomized Clinical Trial.},
journal = {International journal of telerehabilitation},
volume = {17},
number = {2},
pages = {6716},
pmid = {41445680},
issn = {1945-2020},
abstract = {OBJECTIVE: Compare the effects of physiotherapist-supervised synchronous telerehabilitation (TR) with unsupervised asynchronous TR in adults diagnosed with post-COVID syndrome (PCS).<br><br>METHODS: In this single-blind randomized controlled trial conducted with 31 participants with PCS were randomized into a synchronous telerehabilitation (STR) group, which underwent two-hour sessions per week for eight weeks, and an asynchronous telerehabilitation (ATR) group, which performed unsupervised exercises. Lower limb functional strength (Five Times Sit-to-Stand Functional Test) as the primary outcome, and the dyspnea (Modified Medical Research Council), fatigue (Fatigue Assessment Scale), stress, anxiety, depression (Depression, Anxiety, and Stress Scale-21), and quality of life (World Health Organization Quality of Life-BREF Questionnaire) were assessed remotely at the baseline, after 8 weeks of intervention, and at a 20-week follow-up. Data were analyzed using a mixed-model analysis of variance.<br><br>INTERVENTION: Participants were randomized into a synchronous telerehabilitation (TRS) group, which performed two-hour sessions per week for eight weeks, and an asynchronous telerehabilitation (TRA) group, which performed the same exercise protocol but without the supervision of a physiotherapist. Instructional videos were made available via social media (WhatsApp and YouTube). Participants were also instructed to perform the protocol twice a week for eight weeks.<br><br>RESULTS: A statistically significant difference was only observed in lower limb functionality between both groups (p = 0.02). The STR group demonstrated significant improvements in lower limb functional strength (p = 0.03), dyspnea (p = 0.02), fatigue (p = 0.00), stress (p = 0.03), and quality of life (p = 0.00), without any adverse events. Conversely, the ATR group experienced significant improvements in fatigue (p = 0.00) and anxiety (p = 0.02).<br><br>CONCLUSION: The present findings show that both modalities demonstrated positive effects over an 8-week TR program in adults with PCS. However, the synchronous approach achieved greater improvements in lower limb functionality, dyspnea, fatigue, stress, and quality of life. Our findings revealed that asynchronous model was associated with higher dropout rates and suggest synchronous TR may offer advantages regarding treatment adherence.},
}
@article {pmid41444262,
year = {2025},
author = {Wilson, JE and Gurdasani, D and Helbok, R and Ozturk, S and Fraser, DD and Filipović, SR and Peluso, MJ and Iwasaki, A and Yasuda, CL and Bocci, T and Priori, A and Altmann, D and Alwan, NA and Wesley Ely, E},
title = {COVID-19-associated neurological and psychological manifestations.},
journal = {Nature reviews. Disease primers},
volume = {11},
number = {1},
pages = {91},
pmid = {41444262},
issn = {2056-676X},
mesh = {Humans ; *COVID-19/complications/psychology/physiopathology/epidemiology ; *Nervous System Diseases/etiology/virology ; *Mental Disorders/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anxiety/etiology ; Depression/etiology ; },
abstract = {Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5-20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must be tailored based on a patient's presenting symptoms.},
}
@article {pmid41442105,
year = {2026},
author = {Riste, L and Perrin, R and Mulholland, T and Hann, M and McDonald, O and Heald, A},
title = {Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT).},
journal = {Infectious diseases and therapy},
volume = {15},
number = {2},
pages = {577-589},
pmid = {41442105},
issn = {2193-8229},
support = {FORME 5//Stiftelsen f&#xf6;r Synskadade i f.d. Malm&#xf6;hus l&#xe4;n/ ; },
abstract = {INTRODUCTION: Long COVID-related fatigue affects a large number of people across the world, with increasing numbers of people experiencing long-term disability as a consequence. We tested the feasibility of a self-help version of a manual osteopathic approach initially developed for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to treat people with long COVID-related fatigue.<br><br>METHODS: Our feasibility study assessed recruitment into a 1:1 randomized controlled trial (RCT) to receive (i) self-help intervention (self-massage, mobility, flexibility, and breathing exercises, and alternating cold and warm packs to the top of the spine) or (ii) wait-list control group. Follow-up was assessed by online surveys at 3 and 6&#xa0;months (indicating retention). Verbal feedback was obtained from participants.<br><br>RESULTS: Of the 138 eligible survey participants, 126 (90.6%) agreed to participate in two RCTs, achieving the required sample size of 100. Follow-up rates of 79.3% and 59.4% were achieved at 3 and 6&#xa0;months, respectively. Improvements in Chalder Fatigue Questionnaire (CFQ) scores were observed in both groups between 0 and 3&#xa0;months (-&#x2009;4.6 and -&#x2009;2.9, respectively), to a greater degree in the intervention group (p&#x2009;=&#x2009;0.01). Feedback showed a cohort keen to engage with the intervention, although some found the intervention onerous at times.<br><br>CONCLUSIONS: We have reported the results of a feasibility study examining a potentially beneficial intervention for people with long COVID. There were indications of benefit in a patient group with often intractable symptoms. Based on this feasibility study, we believe that the low-cost self-help intervention in isolation could help support fatigue reduction in some people. This has implications for the treatment of both long COVID and ME/CFS.<br><br>TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 99840264.},
}
@article {pmid41441042,
year = {2025},
author = {Cai, E and Kouznetsova, VL and Tsigelny, IF},
title = {Metabolomics-Based Machine Learning Diagnostics of Post-Acute Sequelae of SARS-CoV-2 Infection.},
journal = {Metabolites},
volume = {15},
number = {12},
pages = {},
pmid = {41441042},
issn = {2218-1989},
abstract = {Background: COVID-19 has taken millions of lives and continues to affect people worldwide. Post-Acute Sequelae of SARS-CoV-2 Infection (also known as Post-Acute Sequelae of COVID-19 (PASC) or more commonly, Long COVID) occurs in the aftermath of COVID-19 and is poorly understood despite its widespread effects. Methods: We created a machine-learning model that distinguishes PASC from PASC-similar diseases. The model was trained to recognize PASC-dysregulated metabolites (p ≤ 0.05) using molecular descriptors. Results: Our multi-layer perceptron model accurately recognizes PASC-dysregulated metabolites in the independent testing set, with an AUC-ROC of 0.8991, and differentiates PASC from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, postural orthostatic tachycardia syndrome (POTS), and irritable bowel syndrome (IBS). However, it was unable to differentiate fibromyalgia (FM) from PASC. Conclusions: By creating and testing models pairwise on each of these diseases, we elucidated the unique strength of the similarity between FM and PASC relative to other PASC-similar diseases. Our approach is unique to PASC diagnosis, and our use of molecular descriptors enables our model to work with any metabolite where molecular descriptors can be identified, as these descriptors can be generated and compared for any metabolite. Our study presents a novel approach to PASC diagnosis that partially circumvents the lengthy process of exclusion, potentially facilitating faster interventions and improved patient outcomes.},
}
@article {pmid41440526,
year = {2025},
author = {László, SA and Ianoși, ES and Văsieșiu, AM and Szathmáry, M and Ianoși, MB and Rachiș, DL and Nistor, G and Jimborean, G},
title = {COVID-19 and Lung Cancer Interactions: A Literature Review.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
pmid = {41440526},
issn = {2076-3271},
mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Lung Neoplasms/epidemiology/diagnosis/virology ; SARS-CoV-2 ; Incidence ; Pandemics ; },
abstract = {This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- and mid-stage diagnostic process, which causes a shift to late-stage lung cancer discovery with no impact on its actual prevalence, an alternative hypothesis based on the intersection of viral and cancer biology could have a real effect on lung carcinogenesis as an independent phenomenon. By weaving together population-level trends, mechanistic insights, and translational oncology, we discuss whether the pandemic-associated decline in lung cancer diagnoses reflects primarily a temporary diagnostic artifact or whether it also reveals biologically relevant intersections between SARS-CoV-2 and pulmonary oncogenesis. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted profound and multifaceted effects on global healthcare systems, altering patterns of disease detection, management, and outcomes across nearly all medical disciplines. These disruptions generated what has been termed a "diagnostic deficit", producing a backlog of undetected cancers that have only partially been recovered in subsequent years. This phenomenon, sometimes described as a "COVID-19 debt" in oncology, is thought to contribute to excess late-stage diagnoses and potentially worse medium-term survival outcomes. Beyond the disruption of medical systems, the pandemic also raised a more speculative but biologically intriguing question: could SARS-CoV-2 infection itself, through direct or indirect mechanisms, influence lung cancer biology? Our review aims to critically synthesize the evidence across seven domains to address this dual hypothesis. (1) We examine the observed effects of the pandemic on cancer incidence, highlighting global registry and health-system data; (2) we review SARS-CoV-2 infection biology, including viral entry, replication, protein functions, and treatment implications; (3) we summarize the pathogenesis of lung cancer; (4) we explore the role of immune checkpoints in tumor immune evasion, followed by (5) analyses of immune dysregulation in acute infection and (6) in long COVID; and (7) finally, we evaluate proposed oncogenic mechanisms of SARS-CoV-2, integrating molecular virology with cancer immunology. We conclude that the "diagnostic deficit" phenomenon was a reality during and immediately post-pandemic. However, a definitive answer to the questions related to the impact of the infection as an independent phenomenon would require advanced research information covering the biology of the viral infection and lung cancer oncogenesis: processes that are not currently implemented in routine clinical laboratory investigations.},
}
@article {pmid41439932,
year = {2025},
author = {Zuñiga-Jimenez, CT and Rojas-Esguerra, DF and Muñoz-Martinez, AP and Mendoza-Guzman, DC and Daza-Arana, JE},
title = {Musculoskeletal Sequelae of Post-COVID-19 Syndrome: A Systematic Review.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {41439932},
issn = {2079-9721},
abstract = {Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient's quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case-control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients' daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients.},
}
@article {pmid41439849,
year = {2025},
author = {Bowers, K and Benoit, S and Rose, J and Beck, AF and Folger, AT and Calhoun, TN and Day, ME and Lovell, A and Amin, M},
title = {High Household Transmission Among Asymptomatic Contacts Across Pandemic Waves in Cincinnati, Ohio.},
journal = {Epidemiologia (Basel, Switzerland)},
volume = {6},
number = {4},
pages = {},
pmid = {41439849},
issn = {2673-3986},
support = {UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1TR001425-05A1/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND/OBJECTIVES: COVID-19 and long COVID remain prevalent, with household transmission being an important mode of spread. To quantify household transmission of subclinical SARS-COV-2 infection and identify sociodemographic risk factors that may explain disparities in transmission, we conducted a case-ascertained antibody surveillance study of households in Cincinnati, Ohio.<br><br>METHODS: A partnership was formed between the Cincinnati Health Department and Cincinnati Children's Hospital Medical Center. The Health Department identified cases of COVID-19. Infected individuals, along with their household contacts (n = 245), completed multiple questionnaires about symptoms, demographics, psychosocial (Adverse Childhood Experiences Scale and Everyday Discrimination Scale) and social risk factors, and conditions before and during the pandemic. In addition, they completed a non-fasting blood draw for IgG, IgM, IgA, and nucleocapsid protein serology testing.<br><br>RESULTS: Household contacts experienced few symptoms of COVID-19. However, according to the presence of the nucleocapsid protein, nearly 50% contracted the SARS-CoV-2 virus. This rate was similar by vaccination status but it was higher for household contacts who experienced high levels of early life adversity compared with those with lower levels.<br><br>CONCLUSIONS: Our results confirm the high transmission of subclinical disease among household contacts, which may vary due to psychosocial factors. This reinforces the importance of isolating cases to prevent transmission, regardless of vaccination status.},
}
@article {pmid41438970,
year = {2025},
author = {Oostwouder, CJ and Vos, K and Lutke Schipholt, IJ and Merkus, MR and Telders, T and van Deursen, DFA and de Smit, MB and van Eijk, MD and Bontkes, HJ and Bouwman, FH and Wüst, RCI and de Jong, L and van Hulst, M and Twisk, JWR and van Kalken, CK and Scholten-Peeters, GGM},
title = {Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study.},
journal = {EClinicalMedicine},
volume = {90},
number = {},
pages = {103681},
pmid = {41438970},
issn = {2589-5370},
abstract = {BACKGROUND: Post-COVID involves persistent, multisystem symptoms which are associated with inflammation, immune dysregulation, and autonomic dysfunction. The effects of currently applied treatments for post-COVID are limited. This study assessed the effectiveness of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of post-COVID.<br><br>METHODS: This interrupted time series study was conducted at a Dutch outpatient clinic between August 2024 and April 2025. Adults with physician-diagnosed post-COVID (n = 103) underwent a 4-week pre-treatment observation followed by 24-36 weeks of home-based subcutaneous lidocaine 5% with HP-&#x3b2;-CD, administered using a 3-phase protocol: 500 mg every other day (weeks 1-7), 500 mg daily (weeks 7-14), and up to 1000 mg/day (after week 14, in non-responders). The primary outcome was health-related quality of life (Short Form-12 (SF-12), physical and mental component summary scores). Secondary outcomes included symptom burden (daily app-based questionnaire) and adverse events.<br><br>FINDINGS: Among 103 participants (mean [SD] age 48&#xb7;1 [13&#xb7;0] years; 67% women; median [IQR] symptom duration 31&#xb7;5 [24&#xb7;3-43&#xb7;3] months), 76% completed 24 weeks and 71% completed 36 weeks of treatment. At week 24, the physical and mental component scores increased by 2&#xb7;20 and 5&#xb7;16 points, respectively; at week 36, by 4&#xb7;13 and 7&#xb7;00 points (all p < 0&#xb7;0001). Twenty-seven of 30 symptoms improved significantly at week 24 of treatment compared to pre-treatment. Mild adverse events occurred in 89% of participants, mostly injection-site reactions; no serious adverse events were reported.<br><br>INTERPRETATION: Subcutaneous lidocaine-HP-&#x3b2;-CD was associated with significantly improved quality of life and symptom burden in patients with post-COVID. This home-administered intervention offers a scalable and potentially disease-modifying approach for a disabling condition with no approved treatment to date.<br><br>FUNDING: Excellent Care Clinics funded the treatment provided in this study.},
}
@article {pmid41438927,
year = {2025},
author = {Cheng, AL and Barker, R and von Nordheim, D and McQueen, A},
title = {Long COVID: What is it? Who has it? What Are Treatment Resources in Missouri?.},
journal = {Missouri medicine},
volume = {122},
number = {6},
pages = {488-494},
pmid = {41438927},
issn = {0026-6620},
mesh = {Humans ; Missouri/epidemiology ; *COVID-19/epidemiology/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {As we pass the five-year mark since the COVID-19 pandemic hit, the prevalence of persistent (and often disabling) symptoms from the SARS-CoV-2 virus is estimated to be on par with the prevalence of heart disease. Yet, these Long COVID symptoms can masquerade as other conditions and/or normal aging, so it is believed that Long COVID is under-diagnosed and, as a result, under-treated. Although there is not yet a true cure for Long COVID, many patients benefit substantially from rehabilitation strategies, medications, and social support resources that are available in Missouri. The purpose of this article is to review the definition and epidemiology of Long COVID, provide practical guidance for Long COVID assessment and management especially in the primary care setting, and increase awareness of regional resources for people in Missouri who are living with Long COVID and for the clinicians who are caring for them.},
}
@article {pmid41436401,
year = {2025},
author = {Delano, P and Serra-Sutton, V and Rodriguez-Arjona, D and Benavides, FG and Vives, A and Utzet, M},
title = {Long COVID and its impact on healthcare worker's job performance. A qualitative study in Spain.},
journal = {Journal of occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/JOM.0000000000003650},
pmid = {41436401},
issn = {1536-5948},
abstract = {OBJECTIVE: To explore the experiences of healthcare workers (HCWs) in Spain with long COVID and its impact on their job performance, from the perspectives of affected HCWs, healthcare providers, and key stakeholders.<br><br>METHODS: A phenomenological, constructivist approach was used. Seven online focus groups and four interviews were conducted from April to June 2024. Transcripts were thematically analysed using Atlas.ti using a predefined guideline.<br><br>RESULTS: Long COVID significantly impaired work ability due to physical and cognitive limitations. Sick leave followed long-term or intermittent patterns, though many HCWs hesitated to take leave. Return-to-work experiences were shaped by workplace adaptations, institutional support, and persistent symptoms. Improvement proposals include formal recognition and holistic workplace support as they are essential to reduce its occupational burden.<br><br>CONCLUSIONS: Long COVID significantly impacts affected HCWs job performance, highlighting a need for recognition, support and workplace adaptation.},
}
@article {pmid41432873,
year = {2025},
author = {Michael, HU and Aste, FG and Brouillette, MJ and Fellows, LK and Mayo, NE},
title = {How do fatigue, cognitive dysfunction, activity and role functioning, and mental health inter-relate in adults with post-COVID-19 syndrome? A structural equation model analysis.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {1},
pages = {3},
pmid = {41432873},
issn = {1573-2649},
mesh = {Humans ; Male ; Female ; *COVID-19/psychology/complications ; *Fatigue/psychology/etiology ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Cognitive Dysfunction/psychology/etiology ; *Mental Health ; Quebec/epidemiology ; SARS-CoV-2 ; Latent Class Analysis ; Aged ; *Activities of Daily Living/psychology ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE: Post-COVID-19 Syndrome (PCS) is associated with persistent fatigue and cognitive symptoms that may disrupt daily functioning and mental health. This study examined interrelationships among fatigue, cognitive function, activity and role functioning, and mental health in individuals with PCS.<br><br>METHODS: We analyzed cross-sectional data from 535 adults in the Quebec Action for Post-COVID (QAPC) cohort who self-identified as experiencing PCS symptoms. Structural Equation Modelling was used to estimate associations among fatigue, self-reported cognitive concerns, cognitive performance, and two latent constructs: activity and role functioning and mental health. Models were adjusted for age, sex, education, race, alcohol use, prior mental health history, and vaccination status.<br><br>RESULTS: Fatigue showed association with mental health (standardized regression coefficient, &#x3b2;_std&#x2009;=&#x2009;0.44, p&#x2009;<&#x2009;0.001), primarily through a direct path (&#x3b2;_std&#x2009;=&#x2009;0.42) and a smaller indirect path via self-reported cognitive concerns (&#x3b2;_std&#x2009;=&#x2009;0.10). Fatigue was also associated with reduced activity and role functioning (&#x3b2;_std&#x2009;=&#x2009;-&#x2009;0.79), which did not mediate its link to mental health. Self-reported cognitive concerns were independently associated with poorer mental health (&#x3b2;_std&#x2009;=&#x2009;0.19). Cognitive performance was positively associated with activity and role functioning (&#x3b2;_std&#x2009;=&#x2009;0.11) but not with mental health. Covariates, including older age, Caucasian ethnicity, and vaccination, were linked to more favourable outcomes.<br><br>CONCLUSION: Fatigue and self-reported cognitive concerns were associated with mental health symptoms in PCS. These findings highlight the value of symptom cluster-based screening to inform referral pathways for cognitive, psychological, and functional support. Longitudinal research is needed to clarify temporal ordering.},
}
@article {pmid41431672,
year = {2025},
author = {Jang, J and Ju, H and Song, GH and Kim, M and Hwang, G and Park, J and Kim, SS},
title = {Korea Disease Control and Prevention Agency Infectious Disease Big Data: Opening, Integration, Outcomes, and Future Directions.},
journal = {Jugan geon-gang gwa jilbyeong},
volume = {18},
number = {49},
pages = {2037-2057},
pmid = {41431672},
issn = {2586-0860},
abstract = {OBJECTIVES: The recurring emergence of novel infectious diseases highlights the need for evidence-based policies grounded in real-world data. This study aimed to examine the strategies of the Korea Disease Control and Prevention Agency (KDCA) in establishing and opening up infectious disease big data and to analyze their policy implications.<br><br>METHODS: The KDCA developed the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service (K-COV-N) cohort by linking coronavirus disease 2019 (COVID-19) cases and vaccination records with the National Health Insurance Service data, providing access to researchers since 2022. In 2024, the Infectious Disease Big Data Platform was launched, releasing standardized and anonymized datasets for 64 notifiable diseases. In addition, the Infectious Disease Statistics Dashboard and open application programming interface via the Public Data Portal have enhanced accessibility for both researchers and the public.<br><br>RESULTS: These open data resources have enabled diverse studies, including vaccine effectiveness evaluation, risk analysis for vulnerable populations, post-acute sequelae of COVID-19 (long COVID) research, and assessment of healthcare system impacts. Furthermore, they bridged research and policy practices, supporting the transition toward preventive health policies and strengthening infectious disease response capacity.<br><br>CONCLUSIONS: The infectious disease big data initiatives of the KDCA have functioned as a core infrastructure for evidence-informed policy-making. Integrating additional domains, such as chronic diseases, national health surveys, injuries, and genomics, and applying artificial intelligence-enabled deep analytics and prediction will provide a stronger foundation for protecting population health and enhancing national health security.},
}
@article {pmid41428252,
year = {2026},
author = {Yet, M and Teo, HS and Kwa, H and Yeo, J and Wang, SSY},
title = {Long COVID: a review of mechanisms and treatment modalities.},
journal = {Inflammopharmacology},
volume = {34},
number = {2},
pages = {1111-1121},
pmid = {41428252},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/therapy/complications/immunology/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; COVID-19 Drug Treatment ; },
abstract = {Long COVID is defined by the World Health Organisation (WHO) as a condition arising within 3 months of an acute COVID infection with symptoms lasting for a minimum of 2 weeks. However, this syndrome is poorly understood and has been recorded to include many systemic manifestations, including neurological, respiratory, cardiovascular, gastrointestinal, dermatological, psychosocial, and metabolic systems. Constitutional symptoms also include fatigue, insomnia, body weight changes, poor attention span, hair loss, sexual dysfunction, myalgia, and joint pain, with fatigue being the most common. Given the various proposed mechanisms published in the literature, the postulated mechanisms and pathways are discussed in this paper to contribute to the understanding of defining this syndrome. In this review article, the authors first explored how endothelial damage from COVID infection can lead to a hypercoagulable state. In addition, the effects of an insufficient initial immune response can lead to viral persistence alongside a potentially prolonged hyperactive immune response that includes a cytokine storm and mast cell activation syndrome. Furthermore, the viral persistence can be exacerbated by antibody-dependent enhancement or complicated by molecular mimicry. Current pharmacological therapies are explored and evaluated to investigate their efficacy in addressing this complex and chronic presentation. This review article has been written after an extensive literature review to increase the understanding and awareness regarding Long COVID, as a sincere effort to direct further research for an effective diagnosis and management.},
}
@article {pmid41426345,
year = {2025},
author = {Blitshteyn, S},
title = {Long COVID: a long road ahead.},
journal = {Oxford open immunology},
volume = {6},
number = {1},
pages = {iqaf010},
pmid = {41426345},
issn = {2633-6960},
abstract = {The SARS-CoV-2 pandemic caused an estimated 400 million people worldwide to experience Long COVID and post-COVID complications leading to significant chronic illness and disability with its devastating physical, societal and economic consequences. Since post-acute infectious syndromes have not been given adequate consideration prior to the pandemic, many millions of people with Long COVID worldwide have been left disabled as currently available therapies are largely symptomatic and only partially effective. A case of a previously healthy woman with Long COVID and post-COVID autonomic dysfunction and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is presented here from the perspective of a physician-patient relationship and a broader context of medical care and public health. Immunologic and autonomic mechanistic factors and therapies as these relate to Long COVID are highlighted. Complexities and issues pertaining to patient care, public health and education of neurologists and other specialists regarding Long COVID, dysautonomia and ME/CFS diagnosis and treatment are discussed, in conjunction with the need to develop and diversify effective therapies for people living with these highly disabling conditions.},
}
@article {pmid41425584,
year = {2025},
author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A},
title = {The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1710571},
pmid = {41425584},
issn = {1664-3224},
mesh = {Humans ; *Autoimmune Diseases/immunology/genetics/etiology ; *Haplotypes ; Genetic Predisposition to Disease ; Autoimmunity ; *Histocompatibility Antigens Class II/genetics/immunology ; Animals ; },
abstract = {The prevalence of autoimmune diseases in contemporary human populations poses a challenge for both medicine and evolutionary biology. This review explores how the ancestral human leukocyte antigen class II (HLA-II) haplotypes DR2-DQ6, DR4-DQ8 and DR3-DQ2 could play a central role in susceptibility to these diseases. We propose that these haplotypes, selected in historical contexts of high infectious pressure, may have been maintained because of their ability to elicit strong T-cell responses against pathogens; however, that antigenic promiscuity may be associated with an increased tendency toward immune hyperreactivity in modern environments. This hyperreactivity, involving proinflammatory cytokines including interferon-gamma (IFN-γ), could contribute to the breakdown of tolerance and the emergence of autoimmunity and related clinical phenomena (e.g., Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome and post-vaccination syndromes), although the evidence for the latter remains limited. Finally, we discuss how chronic infections, immunotherapies, vaccination, obesity and chronic physical stressors may exacerbate this susceptibility and consider the therapeutic implications of integrating HLA-II profiling into clinical practice.},
}
@article {pmid41424383,
year = {2025},
author = {Ashok, D and Liu, T and Nakanishi-Koakutsu, M and Criscione, J and Prakash, M and Tensfeldt, A and Kim, B and Ho, B and Chow, J and Craney, M and Ranek, MJ and Lin, BL and Papanicolaou, K and Sidor, A and Foster, DB and Cho, HC and Pekosz, A and Villano, J and Kim, DH and O'Rourke, B},
title = {Innate immune activation and mitochondrial ROS induce acute and persistent cardiac conduction system dysfunction after COVID-19.},
journal = {JCI insight},
volume = {10},
number = {24},
pages = {},
pmid = {41424383},
issn = {2379-3708},
support = {R01 HL156947/HL/NHLBI NIH HHS/United States ; R01 HL164936/HL/NHLBI NIH HHS/United States ; T32 HL007227/HL/NHLBI NIH HHS/United States ; UH3 TR003271/TR/NCATS NIH HHS/United States ; },
mesh = {Animals ; *COVID-19/complications/immunology/physiopathology ; *Immunity, Innate ; *Arrhythmias, Cardiac/immunology/physiopathology/etiology/virology ; SARS-CoV-2 ; *Reactive Oxygen Species/metabolism ; Humans ; *Heart Conduction System/physiopathology/immunology ; Cricetinae ; Disease Models, Animal ; Male ; Myocytes, Cardiac/metabolism/immunology ; *Mitochondria/metabolism ; Cytokines/metabolism ; Electrocardiography ; Poly I-C ; },
abstract = {Cardiac arrhythmias increase during acute SARS-CoV-2 infection and in long COVID syndrome, by unknown mechanisms. This study explored the acute and long-term effects of COVID-19 on cardiac electrophysiology and the cardiac conduction system (CCS) in a hamster model. Electrocardiograms and subpleural pressures were recorded by telemetry for 4 weeks after SARS-CoV-2 infection, and interferon-stimulated gene expression and macrophage infiltration of the CCS were assessed at 4 days and 4 weeks postinfection. COVID-19 induced pronounced tachypnea and cardiac arrhythmias, including bradycardia and persistent atrioventricular block, though no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped, indicating persistent CCS injury. COVID-19 induced cardiac cytokine expression, connexin mislocalization, and CCS macrophage remodeling. Interestingly, sterile innate immune activation by direct cardiac injection of polyinosinic:polycytidylic acid (PIC) induced arrhythmias similar to those of COVID-19. PIC strongly induced cytokine secretion and interferon signaling in hearts, human induced pluripotent stem cell-derived cardiomyocytes, and engineered heart tissues, accompanied by alterations in excitation-contraction coupling. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by JAK/STAT inhibition or a mitochondrially targeted antioxidant, indicating that SARS-CoV-2 infection indirectly leads to arrhythmias by innate immune activation and redox stress, which could have implications for long COVID syndrome.},
}
@article {pmid41421320,
year = {2026},
author = {Soares, L and Davis, H and Spier, E and Walker, T and Davenport, T and Putrino, D and Peluso, M and Vogel, JM},
title = {Recommended long COVID outcome measures and their implications for clinical trial design, with a focus on post-exertional malaise.},
journal = {EBioMedicine},
volume = {123},
number = {},
pages = {106083},
pmid = {41421320},
issn = {2352-3964},
mesh = {Humans ; *COVID-19/complications/therapy ; *Clinical Trials as Topic ; SARS-CoV-2 ; *Research Design ; COVID-19 Drug Treatment ; Treatment Outcome ; Outcome Assessment, Health Care ; },
abstract = {Long COVID has created a worldwide public health crisis and has no approved treatments or validated biomarkers. We summarize the current challenges and considerations of outcome selection in Long COVID trials, along with recommendations for current trial design and future endpoint validation, with a focus on post-exertional malaise (PEM). We make five overarching recommendations for Long COVID clinical trials: 1) thorough characterisation of baseline disease; 2) collection of longitudinal data; 3) design of a placebo arm to enable comparison of treatment effect relative to the disease natural history; 4) accounting for, and when feasible, measuring PEM; 5) balancing severity, duration, and relevant phenotypes across trial arms and within subgroups to be analysed. We present a list of outcomes that may be considered for Long COVID clinical trials, with a focus on PEM. Crucially, the field of Long COVID clinical trials urgently needs funding and research effort investment to develop and validate outcomes concomitantly with clinical trial research.},
}
@article {pmid41418608,
year = {2026},
author = {Sinclair, JE and Mayfield, HJ and Lu, H and Brown, SJ and Moghaddam, T and Waller, M and Bonner, C and Williams, O and Litt, JCB and Short, KR and Lau, CL},
title = {Estimating risk of long COVID using a Bayesian network-based decision support tool.},
journal = {Vaccine},
volume = {72},
number = {},
pages = {128127},
doi = {10.1016/j.vaccine.2025.128127},
pmid = {41418608},
issn = {1873-2518},
mesh = {Humans ; *COVID-19/epidemiology/complications/prevention &amp; control ; Bayes Theorem ; Risk Factors ; Male ; Female ; Adult ; Middle Aged ; SARS-CoV-2 ; COVID-19 Vaccines ; *Decision Support Techniques ; Comorbidity ; Aged ; Vaccination ; Post-Acute COVID-19 Syndrome ; Hospitalization/statistics &amp; numerical data ; Risk Assessment ; },
abstract = {IMPORTANCE: Long COVID causes substantial health burden globally, affecting over 30 % of adults who have ever had symptomatic COVID-19. Individuals at continued risk of long COVID need better and more accessible information to make choices about vaccines and treatments.<br><br>OBJECTIVE: To quantify modifiable risk factors for having long COVID six months post-infection, and develop a decision support tool for managing the risk factors.<br><br>A Bayesian network (BN) model was developed to estimate the probability of long COVID depending on demographics (sex, age), comorbidities, and modifiable factors (vaccination history, number of previous SARS-CoV-2 infections, and drug treatments during acute infection). Data were sourced from published studies and government reports.<br><br>Outcome measures include probability of hospitalisation, ICU admission, and dying from COVID-19 during the acute infection under different scenarios of demographics, comorbidities, vaccine coverage and effectiveness. The BN also estimates the risk of developing long COVID depending on modifiable risk factors, and persistent symptoms related to specific systems (cardiovascular, gastrointestinal, musculoskeletal, pulmonary, neurological, renal, metabolic, coagulation, fatigue, and mental health).<br><br>RESULTS: Vaccination, receiving drug treatment within three days of acute infection, and avoiding repeated infections are the greatest modifiable influences of long COVID development, decreasing risk by up to 63&#xa0;% under modelled scenarios. The interactive user-friendly web-based decision support tool (https://corical.immunisationcoalition.org.au/longcovid) enables easy access to model outputs, and allows individuals to calculate their personalised probability of long COVID under different scenarios of modifiable risk factors.<br><br>CONCLUSIONS AND RELEVANCE: The decision-support tool can be used by individuals or in conjunction with clinicians for shared decision-making on vaccination, pursuing early drug treatment during acute infection, and continuing protective behaviors such as masking and social distancing. The model can also generate population-level estimates of outcomes to assist public health decision-makers to design better-informed public health policies.},
}
@article {pmid41415584,
year = {2025},
author = {Kvandova, M and Balis, P and Kalocayova, B and Vlkovicova, J and Dobrodenkova, S and Puzserova, A},
title = {Cardiovascular damage and comorbidities related to long COVID: pathomechanisms, prevention, and therapy.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1671951},
pmid = {41415584},
issn = {2297-055X},
abstract = {Long COVID (LC) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems, including cardiovascular. Extensive literature supports an association between SARS-CoV-2 infection and cardiovascular complications and increased cardiovascular risk after infection. The cardiovascular sequelae after SARS-CoV-2 infection have not yet been comprehensively characterized. A growing body of evidence suggests that endothelial dysfunction is a central mechanism in COVID-19 and has also been identified as a key pathogenic mechanism in LC. Although considerable progress has been made in characterizing the epidemiology, clinical course, and biology of LC, many questions remain unanswered. The incomplete understanding of the pathomechanisms of LC has hampered the development of targeted therapies to date. Further research and data are needed to develop effective therapeutic and preventive tools. Based on current literature this review aims to provide an up-to-date overview of the pathomechanisms affecting the cardiovascular system and the potential role of selected micronutrients, vitamins and minerals, and flavonoids as preventive and therapeutic strategies in LC.},
}
@article {pmid41413915,
year = {2025},
author = {Gouraud, C and Ancellin-Geay, A and Verot, C and Bergeras, I and Poudevigne, L and Cormier, L and Gilbert, S and Limosin, F and Lacoste, L and Ribayrol, D and Vedrines, CO and Pitron, V and Mesbahi-Ihadjadene, K and Abdoul, H and Rousseau, J and Kachaner, A and Ranque, B and Thoreux, P and Lemogne, C},
title = {Cognitive behavioral therapy, exercise training, and cognitive remediation for patients with post-COVID-19 condition: protocol of an open-label randomized controlled trial.},
journal = {BMC psychology},
volume = {14},
number = {1},
pages = {141},
pmid = {41413915},
issn = {2050-7283},
support = {AAP CoVID-1//Assistance Publique - H&#xf4;pitaux de Paris/ ; },
abstract = {BACKGROUND: Effective rehabilitation programs targeting transdiagnostic mechanisms of persistent physical symptoms are needed in long COVID. We present a transparency-focused description of the protocol of an open-label randomized controlled trial designed to evaluate the efficacy and tolerance of a multidisciplinary intensive rehabilitation program versus usual care.<br><br>METHODS: After a day-hospital multidisciplinary evaluation program including minimal psychoeducation and personalized recommendations, patients presenting with persistent symptoms after COVID-19 are proposed to participate to the study. The intervention consists of a 6-week rehabilitation program with groups of 3 to 5 patients attending three day-hospital sessions per week. The rehabilitation program combines adapted physical activity (three sessions per week with progressive exertion thresholds), cognitive remediation (two computer-based personalized sessions per week) and cognitive behavioral therapy (CBT, two sessions per week: one group session and one individual session). CBT sessions encompass psychoeducation, cognitive restructuring, behavioral activation and gradual exposure, and problem-solving skills. Our primary outcome is health-related quality of life (HRQoL) at 6&#xa0;months, measured with the Physical Component Score (PCS) of the 12-item Short-Form Health Survey. The secondary outcomes are the Mental Component Score (MCS) at 6&#xa0;months, PCS and MCS at 3&#xa0;months, the main persistent symptoms (fatigue, dyspnea, cognitive complaints, pain) and associated psychological burden at 3 and 6&#xa0;months, and patients&#x2019; satisfaction at 3&#xa0;months. All included patients undergo an inclusion visit including a physical condition evaluation, a neuropsychological assessment, a first consultation with the CBT therapist, and the completion of several questionnaires for the secondary outcomes (Pichot scale, Borg scale, Cognitive Difficulties Scale, pain numeric scale, and Somatic Symptom disorder-B criteria scale). These evaluations are repeated at 3- and 6-month follow-up. All analyses will be performed in intention to treat following CONSORT Statement recommendations.<br><br>DISCUSSION: Our goal is to demonstrate that a multidisciplinary intensive rehabilitation program combining adapted physical activity, cognitive remediation, and CBT leads to an improvement in HRQoL in the long term (i.e., six months after a multidisciplinary evaluation program including minimal psychoeducation and personalized recommendations) in patients with long COVID, while being feasible, acceptable, and safe.<br><br>TRIAL REGISTRATION: NCT number NCT05532904, registration date: 2022&#x2013;09-07.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40359-025-03820-8.},
}
@article {pmid41413539,
year = {2025},
author = {Nielsen, TB and Oestergaard, LG and Hawkins, J and Nielsen, CV and Leth, S and Laursen, CH and Sørensen, D},
title = {How a long COVID rehabilitation intervention works: refining its programme theory through a realist-informed qualitative study.},
journal = {BMC health services research},
volume = {26},
number = {1},
pages = {107},
pmid = {41413539},
issn = {1472-6963},
mesh = {Humans ; *COVID-19/rehabilitation/psychology ; Qualitative Research ; Denmark ; Male ; Female ; SARS-CoV-2 ; Middle Aged ; Interviews as Topic ; Focus Groups ; Adult ; Aged ; },
abstract = {BACKGROUND: Although the majority of individuals infected with SARS-CoV-2 recover without treatment, some individuals experience persistent symptoms (long COVID), which may negatively affect their activities and roles of everyday life, leaving them with a profound rehabilitation need. In response to the emergence of long COVID patients, a Danish municipality developed and implemented a structured, out-patient long COVID rehabilitation intervention (The Long COVID Rehabilitation Intervention). To understand how, why and for whom the intervention works, and its functioning, an exploration of the underlying programme theory is required. We thus aimed to explore the interactions between the intervention mechanisms of change, the implementation context and the expected outcomes of The Long COVID Rehabilitation Intervention to confirm or refine the initial programme theory.<br><br>METHODS: We conducted a qualitative study from a realist perspective. Data comprised 12 individual interviews with patients participating in the intervention, a focus group interview with the health professionals delivering the intervention, and an individual interview with the manager of the rehabilitation centre. Transcripts were coded and analysed using a realist analytical approach, enabling for refinement of the initial programme theory expressed with context-mechanism-outcome configurations.<br><br>RESULTS: We demonstrated a close interconnectedness among the context-mechanism-outcome configurations, with identity transformation as central to the intervention functioning supported by a person-centred rehabilitation approach, patient education, and peer support. Moreover, we identified acceptance as an overarching mechanism across all context-mechanism-outcome configurations, facilitating a reconceptualisation of beliefs, values, and roles. This empowered the patients to navigate and participate in daily life despite ongoing long COVID symptoms.<br><br>CONCLUSION: Overall, the initial programme theory was confirmed but required refinement to contexts and mechanisms. The theorisation of The Long COVID Intervention clarified how, why, and for whom it worked, informing the development of future long COVID and post-viral rehabilitation interventions.},
}
@article {pmid41413200,
year = {2026},
author = {Yang, S and Datta, D and Krienen, FM and Woo, E and May, A and Anderson, GM and Galvin, VC and Gonzalez-Burgos, G and Lewis, DA and Ling, E and McCarroll, SA and Arnsten, AF and Wang, M},
title = {Kynurenic acid signaling expands in human and nonhuman primates and impairs dorsolateral prefrontal cortical cognition that is key to mental illness.},
journal = {Molecular psychiatry},
volume = {31},
number = {2},
pages = {1190-1200},
pmid = {41413200},
issn = {1476-5578},
support = {RF1 AG083090/AG/NIA NIH HHS/United States ; 2015276//National Science Foundation (NSF)/ ; },
mesh = {Animals ; *Kynurenic Acid/metabolism ; Humans ; Male ; Cognition/physiology ; Prefrontal Cortex/metabolism ; Macaca mulatta ; Kynurenine/metabolism ; Signal Transduction/physiology ; *Dorsolateral Prefrontal Cortex/metabolism ; Female ; Neurons/metabolism ; Cognitive Dysfunction/metabolism ; Memory, Short-Term/physiology ; Mental Disorders/metabolism ; Tryptophan/metabolism/blood ; Macaca ; Aging/metabolism ; Neuroinflammatory Diseases/metabolism ; alpha7 Nicotinic Acetylcholine Receptor/metabolism ; Neuroglia/metabolism ; Transaminases ; },
abstract = {Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, where impairments are correlated with kynurenine inflammatory signaling. Kynurenine synthesis from tryptophan is increased under conditions of inflammation, then further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may contribute to higher cognitive deficits in these disorders. The current study employed several methods to examine the expression of KYNA and its synthetic enzyme, KAT II, in primate dlPFC, and to determine its effects on working memory-related dlPFC neuronal firing and cognitive functioning in aging macaques with naturally-occurring neuroinflammation. We found that KYNA, its synthetic enzyme, KAT II, and the gene encoding KAT II (AADAT), have greatly expanded expression in macaque and human dlPFC in both glia and neurons, with AADAT especially prominent in primate neurons compared to rodent PFC. In macaques, like humans, plasma kynurenine/tryptophan ratios increased with age, consistent with age-related increasing inflammation. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys. These data show that KYNA inflammatory signaling expands in primate dlPFC, and that inhibition of kynurenine-KYNA production may provide a powerful therapeutic avenue for treating higher cognitive deficits in neuroinflammatory disorders.},
}
@article {pmid41412286,
year = {2025},
author = {Zahiriharsini, A and Rostami, M and Hurd, C and Vakilian, F and Brar, G and Wang, T and Mullie, T and Basiuk, S and Mann, B and Castilho, CD and Smith, M and Lam, G and Ho, C and Manhas, KP},
title = {Evaluating medical and rehabilitation programs for long COVID: utilization, health outcomes, and healthcare costs.},
journal = {The American journal of the medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjms.2025.12.780},
pmid = {41412286},
issn = {1538-2990},
abstract = {BACKGROUND: Long COVID presents a substantial and evolving challenge to individuals and health systems. Despite growing interest in interdisciplinary care models, empirical evidence on their structure, utilization, and effectiveness remains limited. This study examined the delivery and outcomes of specialized outpatient programs for long COVID in Alberta, Canada, focusing on: (a) patterns of program utilization; (b) patient-reported health outcomes; and (c) impacts on healthcare system utilization and costs.<br><br>METHODS: A retrospective observational study was conducted using administrative health records, electronic medical records, and patient-reported outcome measures (PROMs) between April 2022 and September 2023. Adults (&#x2265;18 years) with persistent symptoms &#x2265;12 weeks post-infection were included. Healthcare utilization and costs were assessed over 180-day pre- and post-enrollment periods. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER).<br><br>RESULTS: Of 2819 referrals, 81% (n = 2287) were accepted. Most patients were female (68%), aged 48.2 years on average, and referred by community physicians. Site-level differences were observed in staffing models, care delivery modalities, and wait times. Following enrollment, patients reported small but statistically significant improvements in functional status and quality of life. Symptoms of depression, as measured by the PHQ-9, decreased by an average of 0.9 points (p < 0.05), though below thresholds for clinical significance. Anxiety levels, assessed by the GAD-7, did not change significantly. EQ-5D VAS scores improved by 4.6 points (p = 0.003). Modest reductions in inpatient, ambulatory, and physician service costs were observed. The ICER was $31,140 per quality-adjusted life year (QALY), approaching the Canadian cost-effectiveness threshold.<br><br>CONCLUSIONS: In this observational analysis, program participation was associated with small improvements in patient-reported health status and modest cost patterns. Because natural recovery, regression to the mean, and concurrent system changes may also explain these trends, the findings should be interpreted as preliminary associations rather than causal effects. Prospective controlled studies are needed to confirm effectiveness and economic value.},
}
@article {pmid41411839,
year = {2026},
author = {Calik, I and Peker, Y},
title = {REM - predominant obstructive sleep apnea in adults with a history of COVID-19 infection: A case-control study.},
journal = {Sleep medicine},
volume = {139},
number = {},
pages = {108729},
doi = {10.1016/j.sleep.2025.108729},
pmid = {41411839},
issn = {1878-5506},
mesh = {Humans ; *Sleep Apnea, Obstructive/epidemiology/physiopathology ; *COVID-19/complications/epidemiology ; Female ; Male ; Case-Control Studies ; Middle Aged ; Adult ; Polysomnography ; *Sleep, REM/physiology ; Prevalence ; Fatigue/epidemiology ; SARS-CoV-2 ; Aged ; },
abstract = {STUDY OBJECTIVES: An association between COVID-19 and obstructive sleep apnea (OSA) has been reported in literature. We aimed to address the occurrence and phenotypes of OSA in adults with a history of COVID-19 infection and its possible association with long-COVID.<br><br>METHODS: In this matched case-control study, 152 individuals with a history of COVID-19 and 152 without were evaluated in a sleep laboratory. Groups were matched for age, sex, and body mass index. OSA was defined as an apnea-hypopnea index (AHI) &#x2265;15/h. Rapid Eye Movement (REM)-predominant OSA was defined as AHI &#x2265;15/h and REM-AHI/non-REM-AHI &#x2265;2. Fatigue, reported as "frequent/very frequent," was used as a surrogate marker of long-COVID.<br><br>RESULTS: The prevalence of OSA was significantly lower in the case group (50.0&#xa0;%) compared to the control group (77.6&#xa0;%) (p&#xa0;<&#xa0;0.001). However, 36 cases (47.4&#xa0;%) exhibited REM-predominant OSA while 21 controls (17.8&#xa0;%) demonstrated this phenotype (p&#xa0;<&#xa0;0.001). In a multiple logistic regression analysis, there was a significant correlation between prior COVID-19 infection and the occurrence of REM-predominant OSA (Odds ratio [OR] 3.14; 95&#xa0;% confidence interval [CI] 1.89-5.25; p&#xa0;<&#xa0;0.001). Fatigue was observed in 52.8&#xa0;% of patients with REM-predominant OSA and 35.7&#xa0;% of patients without REM-predominant OSA (p&#xa0;=&#xa0;0.033). In the entire cohort, the factors determining the fatigue were female sex (OR 2.02; 95&#xa0;% CI 1.12-3.64, p&#xa0;=&#xa0;0.019) and REM-predominant OSA (OR 2.18; 95&#xa0;% CI 1.29-3.69; p&#xa0;=&#xa0;0.004).<br><br>CONCLUSIONS: REM-predominant OSA is highly prevalent among individuals with prior COVID-19 infection and is significantly associated with fatigue, underscoring the need to recognize this phenotype in the evaluation and management of Long-COVID.},
}
@article {pmid41410771,
year = {2025},
author = {Petrova, B and Syphurs, C and Culhane, AJ and Chen, J and Chen, E and Cotsapas, C and Esserman, D and Montgomery, RR and Kleinstein, SH and Smolen, KK and Mendez, K and , and Lasky-Su, J and Steen, H and Levy, O and Diray-Arce, J and Kanarek, N},
title = {MTHFR allele and one-carbon metabolic profile predict severity of COVID-19.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {51},
pages = {e2509118122},
pmid = {41410771},
issn = {1091-6490},
support = {U19 AI089992/AI/NIAID NIH HHS/United States ; U19 AI118608/AI/NIAID NIH HHS/United States ; AI118608//HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases (DMID)/ ; AI089992//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {Humans ; *COVID-19/genetics/metabolism/blood ; *Methylenetetrahydrofolate Reductase (NADPH2)/genetics/metabolism ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Severity of Illness Index ; *Carbon/metabolism ; Alleles ; *Metabolome ; Metabolomics ; Aged ; Adult ; Methionine/metabolism ; },
abstract = {While the public health burden of SARS-CoV-2 infection has lessened due to natural and vaccine-acquired immunity, emergence of less virulent variants, and antiviral medications, COVID-19 continues to take a significant toll. There are thousands of new hospitalizations and hundreds of deaths per week in the United States, many of whom develop long COVID. Early identification of individuals at high risk of severe COVID-19 is key for monitoring and supporting respiratory status and improving outcomes. Therefore, precision tools for early detection of patients at high risk of severe disease can reduce morbidity and mortality. Here, we report an untargeted, longitudinal plasma metabolomics study of COVID-19 patients. One-carbon metabolism, a pathway previously shown as critical for viral propagation and disease progression, and a potential target for COVID-19 treatment, scored strongly as differentially abundant in patients with severe COVID-19. Targeted metabolite profiling revealed that one arm of the one-carbon metabolism pathway, the methionine cycle, is a major driver of the metabolic profile associated with disease severity. Further, genomic data from the profiled patients revealed a genetic contributor to methionine metabolism and identified the C677T allele of the MTHFR gene as a preexisting contributor to disease trajectory-patients that show aberrant one-carbon metabolite levels and that are homozygous for the MTHFR C677T, have higher incidence of severe COVID. Our results raise the possibility that MTHFR variant status may inform precision COVID-19 treatment strategies.},
}
@article {pmid41408839,
year = {2026},
author = {Pasternak Taschner, N},
title = {Social long COVID: impacts of the COVID-19 pandemic on public health and policy in Brazil.},
journal = {International journal of epidemiology},
volume = {55},
number = {Supplement_1},
pages = {i44-i45},
pmid = {41408839},
issn = {1464-3685},
}
@article {pmid41408718,
year = {2025},
author = {Ryu, S and Slocum, EM and Whittington, B and Arciniega, LZ and Ahmed, S and Fleischer, NL},
title = {Prospective Associations of Long COVID with Sleep Health Nearly 3 Years After SARS-CoV-2 Infection: A Statewide Representative Cohort Study.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf405},
pmid = {41408718},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: While many adults with Long COVID experience sleep problems, the long-term relationship between Long COVID and sleep remains poorly understood. We investigated how Long COVID is prospectively associated with sleep duration, sleep quality, and sleep disturbance using a population-based cohort of Michigan adults with COVID-19 (n=2,406).<br><br>METHODS: Long COVID was defined at baseline as reporting a recovery time of 90 days or more after the initial infection and sleep outcomes were assessed at follow-up 1 and 2, approximately 1.5 years and 3 years after the initial infection. We estimated linear and multinomial logistic regression models with sleep duration as continuous and categorical variables, respectively. Then, we conducted multinomial logistic regression models for sleep quality and modified Poisson regression for moderate-to-severe sleep disturbance.<br><br>RESULTS: Long COVID was prospectively associated with a shorter sleep duration by 0.35 hours (95% CI: -0.53, -0.17) at follow-up 1. Relative to sleeping 6-9 hours, Long COVID was associated with sleeping <6 hours at follow-up 1 (aRRR: 3.27; 95% CI: 2.16, 4.96) and follow-up 2 (aRRR: 1.91; 95% CI: 1.28, 2.85). Additionally, Long COVID had a strong association with poor-to-very poor sleep quality at both follow-up periods relative to very good-to-fair sleep quality at both follow-up periods. Long COVID was also associated with a 1.53 times higher risk of moderate-to-severe sleep disturbance (95% CI: 1.23, 1.91).<br><br>CONCLUSION: Long COVID was prospectively associated with unhealthy sleep outcomes 3 years after onset. There is a need to enhance sleep health among individuals with Long COVID.},
}
@article {pmid41407606,
year = {2025},
author = {Ouksel, H},
title = {[Long covid pulmonary rehabilitation].},
journal = {Revue des maladies respiratoires},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.rmr.2025.12.001},
pmid = {41407606},
issn = {1776-2588},
abstract = {While the SARS-CoV-2 pandemic has left a lasting impression, the long-term effects of this virus, such as persistent symptoms or long COVID, remain unclear. However, recommendations from learned societies for improving these symptoms exist and are being applied by a number of respiratory rehabilitation centers. In this paper, we provide a summary of the specificities of long COVID care in the context of respiratory rehabilitation, particularly as regards respiratory symptoms, fatigue, cognitive disorders, and cardiovascular symptoms and, more specifically, vegetative dysautonomia. The key elements of support are Therapeutic Patient Education (TPE) and activity management and fractionated exercise (PACING). While the effects of respiratory rehabilitation are highly promising, with potential improvement in symptoms and exercise capacity, the level of evidence remains low to moderate. Structured and coordinated multidisciplinary work is of paramount importance as a means of providing for these individuals the best possible support on their road to recovery. Further studies are needed to improve the level of evidence on the effectiveness of rehabilitation in cases of long COVID.},
}
@article {pmid41407484,
year = {2025},
author = {Wilson, JC and Liu, KY and Mittelman, E and Bareke, P and Shleifer, E and Howard, R},
title = {Brain fog with long covid and chemotherapy: systematic review and meta-analysis.},
journal = {BMJ mental health},
volume = {28},
number = {1},
pages = {},
pmid = {41407484},
issn = {2755-9734},
mesh = {Humans ; *COVID-19/complications/psychology ; *Antineoplastic Agents/adverse effects ; *Neoplasms/drug therapy ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; },
abstract = {QUESTION: What are the cognitive, functional and affective characteristics of brain fog in individuals with long covid and following chemotherapy, and how are these features assessed across studies?<br><br>STUDY SELECTION AND ANALYSIS: In March 2024, we conducted a systematic review and meta-analysis of peer-reviewed studies assessing cognition, function or mood in adults (&#x2265;18 years) with brain fog after COVID-19 or chemotherapy. PubMed, Embase and Web of Science were searched systematically according to eligibility criteria to March 2024, with an update in May 2025. Random-effects meta-analyses using the 'dmetar' package (V.0.0.9000) in R V.4.3.1 were performed for studies comparing individuals with and without brain fog. Bias was assessed using the National Institutes of Health Study Quality Assessment Tools.<br><br>FINDINGS: Of 3077 records screened, 65 studies met inclusion criteria: 40 investigated brain fog in long covid and 25 in chemotherapy populations. Considerable variation in assessment tools was observed. Montreal Cognitive Assessment was the most common cognitive test in long covid studies; Functional Assessment of Cancer Therapy-Cognitive Function was most used in chemotherapy studies. Nine long covid studies were eligible for meta-analysis. Compared with controls, individuals with brain fog had significantly lower cognitive performance (Hedge's g=-0.63, 95%&#x2009;CI -1.15 to -0.12), higher fatigue (Hedge's g=2.64, 95%&#x2009;CI 0.41 to 4.86) and more depressive symptoms (Hedge's g=1.48, 95%&#x2009;CI 0.40 to 2.55). Heterogeneity was high (I[2]>70%). No chemotherapy studies were appropriate for meta-analysis, preventing direct comparison of brain fog features between long covid and chemotherapy groups.<br><br>CONCLUSIONS: Brain fog in long covid and chemotherapy populations is associated with cognitive complaints, fatigue and mood disturbance, though assessment methods differ widely. To improve comparability and clinical understanding, we propose adoption of consistent tools and definitions in future studies. This will be a crucial step in generating findings that can be meaningfully compared across populations.<br><br>PROSPERO REGISTRATION NUMBER: CRD42024520549.},
}
@article {pmid41405757,
year = {2025},
author = {Rasouli, R and Hartl, B and D Konecky, S},
title = {Investigation of the synergistic effect of enzymatic and Ultrasound-Induced amyloid microclot degradation.},
journal = {Journal of thrombosis and thrombolysis},
volume = {},
number = {},
pages = {},
pmid = {41405757},
issn = {1573-742X},
abstract = {Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In this study we examine the effects of three fibrinolytic enzymes rtPA, Lumbrokinase, and Nattokinase on plasma-derived amyloid microclots, in combination with ultrasound-induced microstreaming and microbubbles. A lab-on-chip platform was used to expose the clots to ultrasound at 150, 300, and 500 kHz. Quantitative analysis revealed that ultrasound alone significantly disrupted clot structures, particularly at 150 kHz, where mean clot diameter was reduced by over 60% and large-clot count (> 30 μm) dropped by more than 80% compared to controls. The addition of fibrinolytic enzymes, however, did not produce statistically significant effects at 150-300 kHz which indicates that mechanical forces were the dominant contributors to clot disruption. At 500 kHz, where ultrasound alone was less effective, enzymatic treatment moderately enhanced the reduction in large-clot burden. These results show the potential of low-frequency ultrasound as a primary method of amyloid microclot breakdown, with enzyme co-treatment offering limited but measurable effect.},
}
@article {pmid41405529,
year = {2026},
author = {Sawano, M and Spatz, ES and Sanders, L},
title = {Long COVID as Intermediate Physiology: Rethinking Autonomic Dysfunction and Medical Uncertainty.},
journal = {Journal of the American College of Cardiology},
volume = {87},
number = {2},
pages = {231-233},
doi = {10.1016/j.jacc.2025.10.083},
pmid = {41405529},
issn = {1558-3597},
}
@article {pmid41404772,
year = {2025},
author = {Van Patten, R and Keatley, E},
title = {Cognitive rehabilitation for functional neurological disorder.},
journal = {CNS spectrums},
volume = {31},
number = {1},
pages = {e1},
doi = {10.1017/S1092852925100825},
pmid = {41404772},
issn = {1092-8529},
mesh = {Humans ; *Nervous System Diseases/rehabilitation/psychology/complications ; *Conversion Disorder/rehabilitation/psychology ; Cognitive Dysfunction/rehabilitation ; *Cognitive Behavioral Therapy/methods ; Cognitive Training ; },
abstract = {Cognitive problems represent one of the most common symptom dimensions in functional neurological disorder (FND; >80% of patients) and are frequently associated with distress, disability, and difficulties engaging in evidence-based treatments such as psychotherapy. Cognitive difficulties occur across the FND subtypes (eg, seizures, movement disorders, dizziness) but are largely underrecognized and undertreated by healthcare providers. That is, although a variety of interventions are available for primary functional symptoms and mental health comorbidities, there have not been any systematic efforts to date to specifically target cognitive functioning in FND, leaving an important gap in the literature.Cognitive rehabilitation is a flexible approach utilizing diverse techniques aimed at improving cognition and enhancing functional independence in people with neuropsychiatric disorders. Cognitive rehabilitation can have positive impacts (moderate effect sizes) on cognition and everyday functioning across a variety of conditions, including traumatic brain injury, mild cognitive impairment, long COVID, PTSD, and others. Given the transdiagnostic clinical utility of cognitive rehabilitation, it has potential for benefit in many patients with FND if adapted and applied appropriately.In this review, we highlight the utility of cognitive rehabilitation for FND, with a focus on clinically actionable advice and guidance. We describe fundamental principles of cognitive rehabilitation, evidence for its efficacy and effectiveness across neuropsychiatric disorders, and methods for avoiding potential pitfalls when applying it in FND. We then discuss a Case Vignette in order to emphasize the application of cognitive rehabilitation principles in an individual patient. We conclude with future directions for research and clinical care.},
}
@article {pmid41404601,
year = {2025},
author = {Thapaliya, K and Marshall-Gradisnik, S and Inderyas, M and Barnden, L},
title = {Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {50},
number = {},
pages = {101142},
pmid = {41404601},
issn = {2666-3546},
abstract = {BACKGROUND: Diverse neurological symptoms are experienced by long COVID and COVID-19 recovered individuals. However, the long-term effects of SARS-CoV-2 in the brain of both groups are underexplored. This study aimed to investigate changes in tissue microstructural and brain neurochemical levels in long COVID and recovered COVID-19 patients compared to healthy controls.<br><br>METHODS: We recruited 47 participants (long COVID&#xa0;=&#xa0;19, COVID-recovered healthy controls&#xa0;=&#xa0;12, and healthy controls without COVID-19 infection&#xa0;=&#xa0;16) who underwent 3T MRI scans. We acquired T1 and T2 weighted images to assess myelin signal, diffusion weighted images to assess tissue microstructure, and magnetic resonance spectroscopy data to estimate brain neurochemical levels.<br><br>FINDINGS: Our multimodal MRI study showed altered T1w/T2w signal between long COVID vs COVID-recovered-healthy controls, long COVID vs healthy controls, and COVID-recovered-healthy controls vs healthy controls. Furthermore, T1w/T2w signal intensity was significantly correlated with physical and cognitive function. Diffusion weighted imaging also showed altered tissue microstructure in these three group comparisons. However, brain neurochemicals were only significantly different between long COVID vs COVID-recovered-healthy controls.<br><br>INTERPRETATION: This is one of the first studies to report different myelin signal and brain neurochemical changes between long COVID, COVID-recovered-healthy controls, and healthy controls without SARS-CoV-2 infection. These brain changes provide compelling evidence for the long-term effects of SARS-CoV-2 on brain function.},
}
@article {pmid41402665,
year = {2025},
author = {Schuermans, A and Verstraete, A and Lammi, V and Nakanishi, T and Ardissino, M and Van den Eynde, J and Sun, BB and Georgakis, MK and Guillen-Guio, B and Wain, LV and Brightling, CE and , and Van Weyenbergh, J and Lewandowski, AJ and Raman, B and Zeberg, H and Ollila, HM and Burgess, S and Natarajan, P and Honigberg, MC and Freson, K and Vanassche, T and Verhamme, P},
title = {Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry.},
journal = {Nature cardiovascular research},
volume = {4},
number = {12},
pages = {1662-1676},
pmid = {41402665},
issn = {2731-0590},
support = {R01Hl161365//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; 1843423N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 2023.0141//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 2021-03050//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; 22J30004//Japan Society for the Promotion of Science London (JSPS London)/ ; 221680/WT_/Wellcome Trust/United Kingdom ; C14/23/121//KU Leuven (Katholieke Universiteit Leuven)/ ; 512461526//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; #1350181//Academy of Finland (Suomen Akatemia)/ ; G072921N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 302210/WT_/Wellcome Trust/United Kingdom ; 302210/Z/23/Z//Wellcome Trust (Wellcome)/ ; R01AI170850//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; 221680/Z/20/Z//Wellcome Trust (Wellcome)/ ; R01 AI170850/AI/NIAID NIH HHS/United States ; },
mesh = {Female ; Humans ; Male ; Middle Aged ; *COVID-19/genetics/complications/ethnology ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Risk Factors ; *Venous Thromboembolism/genetics ; *White People/genetics ; },
abstract = {SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organs. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and thromboembolism; however, compelling evidence from humans is limited and causal associations remain unclear. In this study, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative (ncases = 3,018; ncontrols = 994,582). Primary analyses revealed that each unit increase in the log odds of genetically predicted venous thromboembolism risk was associated with 1.21-fold odds of long COVID (95% confidence interval (CI): 1.08-1.35; P = 1.2 × 10[-3]). This association was independent of acute COVID-19 severity, was robust across various sensitivity analyses and was replicated in external datasets. Downstream analyses using gene-specific instruments, along with protein and gene expression data, suggested the protease-activated receptor 1 (PAR-1) as a potential molecular contributor to long COVID. These findings provide human genetic evidence implicating shared pathogenetic pathways in thromboembolism and long COVID.},
}
@article {pmid41402664,
year = {2025},
author = {Denorme, F and Campbell, RA},
title = {Linking thromboembolism to the pathogenesis of long COVID.},
journal = {Nature cardiovascular research},
volume = {4},
number = {12},
pages = {1594-1595},
pmid = {41402664},
issn = {2731-0590},
support = {R01 HL163019/HL/NHLBI NIH HHS/United States ; },
}
@article {pmid41397681,
year = {2025},
author = {Kouyoumdjian, JA and Yamamoto, LAR and Graca, CR},
title = {Reply to the letter "Long-COVID may not be explained by skeletal muscle involvement, but rather by other, more compelling pathophysiological concepts".},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {10},
pages = {1-2},
pmid = {41397681},
issn = {1678-4227},
}
@article {pmid41397680,
year = {2025},
author = {Finsterer, J and Scorza, FA and Scorza, CA},
title = {Long COVID may not be explained by skeletal muscle involvement, but rather by other, more compelling pathophysiological concepts.},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {10},
pages = {1-2},
pmid = {41397680},
issn = {1678-4227},
}
@article {pmid41396195,
year = {2026},
author = {Sharma, V and Epstein, R and Arora, MK and Edinger, T and Dahlquist, M and Flessner, C and McCullough, JM and Ghimire, U and Smith, LU and Reina Ortiz, M},
title = {Academic-Nonprofit Partnership for Public Health: Document Analysis and Systematization of the Implementation of a Multijurisdictional Long COVID Surveillance Platform.},
journal = {Journal of public health management and practice : JPHMP},
volume = {32},
number = {2},
pages = {227-236},
pmid = {41396195},
issn = {1550-5022},
mesh = {Humans ; *COVID-19/epidemiology ; *Public Health/methods ; United States/epidemiology ; *Public Health Surveillance/methods ; *Organizations, Nonprofit/organization &amp; administration ; *Health Information Exchange ; Public-Private Sector Partnerships ; SARS-CoV-2 ; Document Analysis ; },
abstract = {CONTEXT: Health information exchanges (HIEs) are generally underutilized as data sources for public health surveillance, potentially decreasing the ability of public health practitioners to leverage the rich, real-time, clinical, and public health data therewith contained.<br><br>OBJECTIVES: To systematize the process of implementing an academic-nonprofit partnership (ANPP) designed to leverage multijurisdictional HIE data for public health surveillance of Long COVID by Systematizing the ANPP's. Implementation, with a focus on its operational strengths, opportunities, challenges, and strategies for its sustained growth.<br><br>DESIGN: Document review and analysis informed by the Centers for Disease Control and Prevention's Surveillance System Evaluation framework. We employed a systematic approach to the collection and interpretation of 5 types of documents to describe the experience of implementing a multistakeholder, multijurisdictional, HIE-based ANPP for public health surveillance from 2022 to 2025.<br><br>SETTING: Multijurisdictional settings in the US.<br><br>PARTICIPANTS: The ANPP and its constituent organizations.<br><br>INTERVENTION: Implementation of the ANPP.<br><br>MAIN OUTCOME MEASURE: Identification of critical lessons learned including key partnership elements, encountered challenges, surveillance framework application, and strategies for implementing a multistakeholder, multijurisdictional ANPP for public health surveillance.<br><br>RESULTS: A participatory, iterative approach was used to engage stakeholders on ANPP implementation. Foundational strengths included complementary partner expertise and robust data environments, which created unique opportunities for comprehensive Long COVID surveillance. Challenges involved navigating varied institutional, legal, and regulatory requirements, complex data permission structures, and coordinating teams across different time zones. Key lessons learned highlighted that extensive initial investment in legal frameworks, data environments, and communication protocols, though time-consuming, significantly improves surveillance capabilities. Strategies to ensure success included replacing large meetings with focused working groups, fostering frequent communication, and implementing rigorous inter-team data quality control.<br><br>CONCLUSION: Implementing multistakeholder, multijurisdictional, HIE-based surveillance necessitates substantial upfront investment. Continuous refinement and strategic efforts are vital for overcoming operational complexities and maximizing HIE potential for robust public health surveillance.},
}
@article {pmid41395800,
year = {2025},
author = {Evans, CR and Echols, MR and Martin, D and Taylor, HA and Washington, JA and Gbinigie, O and Gaglioti, AH and Wright, W and Hovmand, P},
title = {Leveraging Community-Based System Dynamics to Understand Long Covid Disparities in African American Communities: A Model for Health Equity Research.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70516},
pmid = {41395800},
issn = {1369-7625},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Female ; Humans ; Male ; *Black or African American ; *Community Participation ; *COVID-19/ethnology ; *Health Equity ; *Health Status Disparities ; *Healthcare Disparities ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long Covid disproportionately affects African American communities, exacerbating pre-existing health disparities and systemic barriers to care. Conventional public health interventions often fail to address the complex systemic issues at play due to a lack of grounding in community-certified knowledge about the broader societal context that produces the disparities and in which the interventions must operate. New methods are needed to elicit community perspectives on living with long Covid.<br><br>METHODS: This study employed Community-Based System Dynamics (CBSD) workshops, conducted in hybrid formats (online and in-person), to engage African American communities impacted by long Covid. Participants included affected individuals, healthcare professionals and systems researchers.<br><br>RESULTS: The workshops yielded system dynamics causal loop diagrams that illustrate the multifaceted societal context and impact of long Covid. Community-driven insights led to the identification of targeted interventions and informed a comprehensive action plan designed to address specific health system barriers and enhance community resilience.<br><br>CONCLUSIONS: CBSD workshops proved effective in fostering significant community engagement and empowerment, presenting a replicable model for gaining a deeper understanding of the socio-cultural context that underlies complex health disparities. These findings suggest that incorporating community-sourced societal context knowledge and system dynamics modelling and analysis can substantially enhance public health strategies for managing long Covid.<br><br>People with lived experience of long Covid were actively involved throughout all phases of this study. Participants contributed to the design and facilitation of Community-Based System Dynamics (CBSD) workshops, helped construct and refine causal loop diagrams based on their experiences, and generated action ideas for future interventions. Their insights shaped both the structure and content of the system models and directly informed the interpretation of results. Several participants also reviewed and provided feedback on early drafts of the manuscript to ensure the findings reflected their perspectives and priorities.},
}
@article {pmid41394882,
year = {2025},
author = {Padilla-Blanco, M and García-García, T and Grigas, J and López-Ayllón, BD and Garrido, JJ and Oliva, MA and Montoya, M},
title = {Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1726698},
pmid = {41394882},
issn = {1664-3224},
mesh = {Humans ; *SARS-CoV-2/immunology/genetics ; *COVID-19/immunology/virology ; Host-Pathogen Interactions/immunology ; Interferon Type I/immunology/metabolism ; Animals ; *Viral Regulatory and Accessory Proteins/immunology/genetics/metabolism ; Viral Proteins/immunology ; },
abstract = {SARS-CoV-2 accessory proteins (APs), particularly ORF3a and ORF9b, have emerged as key modulators of host-pathogen interaction and potential contributors to long COVID. Of the 13 predicted APs, only nine are expressed during infection - termed Infection-related APs - while the remaining are classified as Putative APs. Despite this distinction, extensive gene overlap among APs underscores the remarkable adaptability of SARS-CoV-2 viral genome. This review delves into the diverse roles of the original Wuhan APs and their Omicron counterparts in shaping host immunity, with an emphasis on their ability to suppress type I interferon (IFN-I) signalling, modulate cellular metabolism, and trigger inflammatory/apoptotic pathways. By integrating immunopathological insights with evolutionary dynamics and structural perspectives, this review provides a comprehensive understanding of the mechanism underlying Omicron's reduced pathogenicity and highlights promising, yet unexplored, therapeutic targets within the SARS-CoV-2 accessory proteome.},
}
@article {pmid41394849,
year = {2025},
author = {Gabig-Cimińska, M},
title = {Dysregulated TFEB-autophagy-lysosome pathway links acute COVID-19 immunopathology to Long COVID sequelae.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1708364},
pmid = {41394849},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/pathology/complications ; *Lysosomes/immunology/metabolism ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/immunology ; *Autophagy/immunology ; *SARS-CoV-2/immunology ; Animals ; Signal Transduction/immunology ; Immunity, Innate ; },
abstract = {SARS-CoV-2 disrupts cellular homeostasis, including the autophagy-lysosome pathway (ALP), a critical component of innate immunity and viral clearance. By subverting autophagy, SARS-CoV-2 proteins such as ORF3a, ORF7a, and NSP6 inhibit autophagosome-lysosome (APG-L) fusion, generating "incomplete autophagy" that permits viral persistence and drives hyperinflammation. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, has emerged as a central player in the host response to coronavirus infection. TFEB orchestrates the expression of genes required for lysosomal function and autophagic flux while also shaping immune processes, including cytokine production, interferon-stimulated gene expression, and inflammasome clearance. This mini review synthesizes current knowledge on the TFEB-ALP axis in COVID-19 pathogenesis, highlighting its influence on acute immunopathology and its potential contribution to post-acute sequelae (Long COVID). Restoring TFEB activity and autophagic flux may counteract SARS-CoV-2 evasion strategies and restrain aberrant inflammatory responses. Harnessing the TFEB-autophagy pathway as a host-directed therapeutic strategy could help rebalance immune homeostasis, limit tissue damage during acute infection, and mitigate persistent inflammatory sequelae in Long COVID.},
}
@article {pmid41393125,
year = {2025},
author = {Halma, M and Varon, J},
title = {Restoring trust in vaccination: listening to patients and acknowledging Post-Acute COVID Vaccine Syndrome.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1688170},
pmid = {41393125},
issn = {2296-858X},
abstract = {The National Academies of Science, Engineering, and Medicine (NASEM) has defined Long COVID as "an infection-associated chronic condition (IACC) that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems." This definition puts the experience of the patient primary, where the decisive factor for diagnosis is a persistent health problem after COVID-19 infection. Ongoing work aims to characterize the biological signature of both Long COVID and Post-Acute COVID-19 Vaccination Syndrome (PACVS), clinicians and researchers are faced with heterogeneous diseases that are not easily captured by a single biomarker. Candidate biomarkers establish spike protein persistence, either through detection of full length spike, the S1 subunit of spike protein, or anti-spike protein antibody positivity. Additionally, to rule out viral reservoirs or active infection as an explanation, anti-nucleocapsid antibody, a hallmark of COVID-19 infection not present in the vaccine, should be negative. Other candidate biomarkers include detection of vaccine sequence mRNA, or sequence differentiation of viral from vaccinal spike through mass spectrometry. Despite candidate biomarkers, medicine is far from a definitive diagnostic test. Lack of diagnosis has created negative experiences for patients and strengthened vaccine hesitancy. An open acknowledgement of vaccine risks is vital to restoring trust in science and medicine and ensuring those injured have access to the care they need.},
}
@article {pmid41388982,
year = {2025},
author = {Leavesley, MR and Dugen-Williams, C and Dobel-Ober, D and Carson, A},
title = {PCE-CfD and Long Covid: An NHS Service Evaluation on the Benefits of Using Person-Centred Experiential Counselling for Depression With People With Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70517},
pmid = {41388982},
issn = {1369-7625},
mesh = {Humans ; *COVID-19/psychology/complications ; Female ; Male ; State Medicine ; Middle Aged ; *Depression/therapy/etiology ; *Counseling/methods ; Adult ; Anxiety/therapy ; Aged ; SARS-CoV-2 ; *Person-Centered Psychotherapy/methods ; United Kingdom ; Cohort Studies ; },
abstract = {BACKGROUND: Long Covid is a condition affecting multiple organ systems and the mental health of patients. To address this, two National Health Service (NHS) services in the West Midlands developed an integrated long-term conditions (LTCs) pathway, co-produced between a 'Post Covid' service and an NHS Talking Therapy service for anxiety and depression (TTAD). Eligible people with Long Covid were offered person-centred experiential counselling for depression (PCE-CfD) to help improve their mental health. Despite limited evidence for PCE-CfD in managing depression linked to LTCs, it was identified that a humanistic approach could help address the disrupted self-narratives that existed with this cohort of patients.<br><br>OBJECTIVE: This NHS service evaluation investigated outcomes from clients with Long Covid who received PCE-CfD, specifically the impact on reduced depression and anxiety symptoms, and improved social and occupational functioning. It analysed pre- and post-treatment client/patient self-reported data using routine outcome measures, including the PHQ-9, GAD-7 and WSAS.<br><br>METHODS: A non-experimental cohort design was used to analyse anonymised routinely collected secondary data. Data that met the inclusion criteria were extracted for treatment delivered between August 2022 and October 2024. Paired t-tests were used to examine whether there were significant improvements between pre- and post-treatment outcome measures.<br><br>RESULTS: For people with Long Covid that completed treatment (n&#x2009;=&#x2009;31), three t-tests were completed showing a significant reduction from PCE-CfD treatment, in depression (p&#x2009;<&#x2009;0.01), anxiety (p&#x2009;<&#x2009;0.01) and social functioning (p&#x2009;<&#x2009;0.05). Cohen's d values indicated a very large effect size for a treatment effect in the reduction of depression (d&#x2009;=&#x2009;2.1) and anxiety symptoms (d&#x2009;=&#x2009;1.2). Recovery rates were analysed, using the NHS Talking Therapy recovery rate calculation, which showed that 83.87% of the people with Long Covid who were treated reached 'recovery', a much higher rate than the 48% NHS England&#xa0;target.<br><br>CONCLUSION: This NHS service evaluation underscores the effectiveness of PCE-CfD in reducing symptoms of depression and anxiety, as well as improving social and occupational functioning. These improvements observed in routine outcome measures highlight the benefits of offering a humanistic approach to people with Long Covid. These small but significant findings offer valuable insights into future service delivery and research in managing mental health challenges associated with chronic health conditions.<br><br>This NHS service evaluation uses secondary data analysis, meaning PPIE did not take place in advance. However, PPIE discussions could arise when disseminating its findings that could lead to further research in this area.},
}
@article {pmid41388153,
year = {2026},
author = {Aid, M and Boero-Teyssier, V and McMahan, K and Dang, R and Doyle, M and Belabbaci, N and Borducchi, E and Collier, AY and Mullington, J and Barouch, DH},
title = {Long COVID involves activation of proinflammatory and immune exhaustion pathways.},
journal = {Nature immunology},
volume = {27},
number = {1},
pages = {61-71},
pmid = {41388153},
issn = {1529-2916},
support = {P51 OD011132/OD/NIH HHS/United States ; U01 CA260476/CA/NCI NIH HHS/United States ; INV-027406, INV-041469//Bill and Melinda Gates Foundation (Bill &amp; Melinda Gates Foundation)/ ; INV-027406/GATES/Gates Foundation/United States ; CA260476//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; S10 OD026799/OD/NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Post-Acute COVID-19 Syndrome/blood/immunology/virology ; *SARS-CoV-2 ; Case-Control Studies ; Convalescence ; *Signal Transduction/immunology ; *Immune System Exhaustion/immunology ; Inflammation ; Biomarkers/blood ; Transcriptome/immunology ; Proteome/immunology ; *Lymphocyte Activation/immunology ; },
abstract = {Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.},
}
@article {pmid41384659,
year = {2025},
author = {Bessalah, S and Sinha, D and Yuan, X and Paul, S and Longet, S},
title = {[Long COVID: therapeutic challenges and opportunities in the face of persistent sequelae].},
journal = {Medecine sciences : M/S},
volume = {41},
number = {11},
pages = {869-876},
doi = {10.1051/medsci/2025185},
pmid = {41384659},
issn = {1958-5381},
mesh = {Humans ; *COVID-19/complications/therapy/epidemiology ; *SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Chronic Disease ; },
abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has not only led to a global health and economic crisis but also renewed attention to a clinical phenomenon of persistent symptoms after viral infection. This phenomenon is defined as long COVID or post-COVID-19 syndrome. Approximately one in eight patients experience persistent symptoms of varying intensity after the acute phase of the infection. This phenomenon, combined with the virus's high transmissibility and rapid mutation rate, poses a major public health challenge. This review examines various therapeutic approaches currently under consideration for treating long COVID, and explores future prospects in this field.},
}
@article {pmid41384154,
year = {2025},
author = {Floridia, M and Weimer, LE and Forte, AL and Palange, P and Ciardi, MR and Rovere-Querini, P and Agostoni, P and Barisione, E and Zucco, S and Andreozzi, P and Bonfanti, P and Figliozzi, S and Tosato, M and Lacedonia, D and Loso, K and Gnerre, P and di Rosolini, MA and Toraldo, DM and Martino, GP and Vagheggini, G and Parati, G and Onder, G and , },
title = {Administration of antivirals, IL-6 inhibitors, monoclonal neutralizing antibodies and systemic corticosteroids in acute SARS-CoV-2 infection do not reduce the subsequent burden of Long-COVID symptoms.},
journal = {Le infezioni in medicina},
volume = {33},
number = {4},
pages = {391-403},
pmid = {41384154},
issn = {2532-8689},
abstract = {PURPOSE: Some studies have suggested that therapeutic interventions able to mitigate the acute phase of COVID-19 can also reduce the risk of Long-COVID and its severity, but the issue is still controversial.<br><br>METHODS: We examined in a national cohort of patients followed in Long-COVID centers the risk of persistent symptoms according to administration in acute COVID-19 of four drug classes: antivirals, IL-6 inhibitors, monoclonal neutralizing antibodies and systemic corticosteroids. Final risk estimates for 26 symptoms were expressed as adjusted odds ratios calculated in multivariable logistic regression models that included as covariates demographics, comorbidities, BMI, smoking, severity of acute disease, hospitalization, level of respiratory support, SARS-CoV-2 vaccination and treatments administered during acute infection.<br><br>RESULTS: The final population included 1534 adult patients (mean age 60.3 years, 67.0% hospitalised during acute COVID-19). Treatments administered during acute phase included systemic steroids (52.8%), antivirals (20.7%, mostly remdesivir), IL-6 inhibitors (9.4%) and neutralizing antibodies (3.9%). After a mean interval of 338 days from acute COVID-19, 1181 patients (77.0%) presented persisting symptoms. For the drug classes considered, some protective associations were found in univariate analyses, that were however not maintained adjusting for confounders in multivariate analyses. Systemic corticosteroids and IL-6 inhibitors showed some negative associations with isolated symptoms.<br><br>CONCLUSIONS: Some drug classes showed a protective effect that was however not confirmed in multivariable analyses, underlining the importance of adjusting for a comprehensive number of covariates. Clinicians should consider the possibility that systemic corticosteroids and IL-6 inhibitors administered during acute COVID-19 may prolong the persistence of particular symptoms.},
}
@article {pmid41381625,
year = {2025},
author = {Lersritwimanmaen, P and Thonghem, A and Wongsrisakunkaew, W and Kositamongkol, C and Phisalprapa, P},
title = {Prevalence and impact of long COVID on health-related quality of life in previously hospitalized COVID-19 patients: a 2-year follow-up study.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {1874},
pmid = {41381625},
issn = {2045-2322},
mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology/complications/psychology ; Male ; Female ; Middle Aged ; Thailand/epidemiology ; Follow-Up Studies ; Prevalence ; Hospitalization ; Adult ; Aged ; SARS-CoV-2/isolation &amp; purification ; Retrospective Studies ; Risk Factors ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Fatigue/epidemiology ; },
abstract = {Long COVID is a major health concern, yet evidence from Southeast Asia remains limited. We evaluated the prevalence, predictors, and health-related quality of life (HRQoL) impact of long COVID among hospitalized adults in Thailand over two years. This single-center, ambidirectional cohort combined retrospective chart review with prospective follow-up. The cohort comprised 295 adults hospitalized for symptomatic COVID-19 between August and November 2021. Interviews occurred at three months, one year, and two years post-infection. Long-COVID prevalence was 49.8% at three months; among these, 64.4% reported persistent symptoms at one year, and 22% of the one-year symptomatic group had symptoms at two years. Common symptoms included breathlessness, fatigue, and memory disturbance. Logistic regression identified severe-critical acute illness as a risk factor (adjusted odds ratio [aOR] 2.06, 95% CI 1.23-3.46), while full vaccination was protective (aOR 0.48, 95% CI 0.25-0.90). Long COVID was associated with lower HRQoL across all EQ-5D-5L domains. Long COVID was frequent among hospitalized Thai patients, with symptoms persisting in a substantial proportion up to two years. Severity of acute COVID-19 and vaccination status predicted long COVID. Long COVID was linked to reduced HRQoL, underscoring the need for follow-up and further confirmation in larger, multicenter studies.},
}
@article {pmid41379191,
year = {2025},
author = {La Scaléa, ACR and Uehara, SCDSA},
title = {Pain in Long COVID: A scoping review of clinical characteristics and patterns of manifestation.},
journal = {Revista latino-americana de enfermagem},
volume = {33},
number = {},
pages = {e4777},
pmid = {41379191},
issn = {1518-8345},
mesh = {Humans ; *COVID-19/complications ; Female ; *Pain/etiology/diagnosis/epidemiology ; Male ; Pain Measurement ; SARS-CoV-2 ; },
abstract = {to map the available scientific evidence on the clinical characteristics and patterns of pain manifestation (location, frequency, duration, intensity, and quality) in individuals with Long COVID. a scoping review of publications from March 2020 to June 2024, indexed across four databases. Study selection was conducted by two independent, blinded reviewers. Data were extracted using a standardized instrument and analyzed descriptively. nineteen studies were included, indicating that pain affects individuals across all age groups, with higher prevalence among women, primarily involving the head, neck, shoulder, lower back, and hip. Pain frequency ranged from daily to monthly episodes, with duration exceeding one year in some cases. Intensity varied from mild to severe, and pain characteristics were diverse, with descriptors including burning, pressure, colicky, and throbbing pain. the clinical characteristics and patterns of pain manifestation in Long COVID are diverse. However, there is a paucity of studies providing detailed analyses of pain features and the influence of individual variables. These findings should guide future research and clinical practice toward a more comprehensive and contextualized assessment of pain in Long COVID.},
}
@article {pmid41377983,
year = {2025},
author = {Salinas, TRW and Freeman, S and Richardson, R and Weng, W and Ali, M and van Schoor, A and Viox, E and Nguyen, K and Auger, J and Ketan, R and Gagne, M and Picou, B and Golden, NA and Vaccari, M and Jean, S and Wood, JS and Cohen, J and Johnson, RP and Douek, DC and Niclou, BA and Levit, RD and Moore, IN and Paiardini, M and Raper, J},
title = {Inflammation from mild COVID-19 results in persistent neurological and behavioral changes in rhesus macaques.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41377983},
issn = {2693-5015},
support = {P51 OD011132/OD/NIH HHS/United States ; P51 OD011104/OD/NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; R01 HL140223/HL/NHLBI NIH HHS/United States ; R01 HL175069/HL/NHLBI NIH HHS/United States ; },
abstract = {Although most SARS-CoV-2 infections result in mild or moderate symptoms not requiring hospitalization, many patients experience persistent symptoms after their initial recovery, a condition termed Post-Acute Sequelae of SARS-CoV-2 infection (PASC). The underlying pathogenesis behind infection associated chronic illnesses, such as PASC, are poorly understood, thus critically limiting the development of therapeutics to prevent or alleviate symptoms. The current study examined the neurocognitive impact of SARS-CoV-2 induced inflammation in a nonhuman primate model. Ten adult rhesus macaques (5 female, 5 male) were monitored before, during, and after recovery from a mild COVID-19 illness (SARS-CoV-2 strain 2019-noCoV/USA-WA1/2020). Macaques exhibited persistent alterations in taste and smell, as well as decreased cognitive flexibility up to 3 months post-infection. Female macaques experienced sleep disturbances, greater stress and poorer autonomic function months after SARS-CoV-2 infection. Importantly, the development of these neurocognitive changes were associated with acute cytokine response to infection and increased microglia activation in brain tissue at 4 months post-infection. These findings suggest a causative link between the inflammatory response to mild COVID-19 symptoms and persistent neurocognitive changes associated with PASC and provide rationale for therapeutic strategies aimed at reducing acute inflammatory responses to the virus.},
}
@article {pmid41377364,
year = {2025},
author = {Rizvi, GS and Ullah, R and Khalid, M and Talha, M and Waafira, A},
title = {Circadian rhythm disruption and melatonin dysregulation as overlooked drivers of immune imbalance and multiorgan failure in post-COVID syndrome: a call for chronotherapy-based interventions.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {12},
pages = {9069-9070},
pmid = {41377364},
issn = {2049-0801},
abstract = {Post-COVID syndrome (long COVID) is increasingly recognized as a state of chronic inflammation, immune imbalance, and multiorgan dysfunction. Emerging evidence highlights circadian rhythm disruption and melatonin dysregulation as overlooked drivers of persistent symptoms such as fatigue, cognitive impairment, and immune dysregulation. Reduced melatonin impairs cytokine suppression, antioxidant defense, and mitochondrial protection, fueling inflammation and oxidative stress. These disruptions, coupled with autoimmune responses targeting adrenergic and muscarinic receptors, exacerbate systemic pathology. Preliminary data suggest that melatonin supplementation and chronotherapy may restore circadian alignment, rebalance immunity, and mitigate disease progression, although robust large-scale trials remain limited. Integrating circadian science into therapeutic protocols may provide a novel avenue for improving long-term outcomes in post-COVID patients.},
}
@article {pmid41375862,
year = {2025},
author = {Alghamdi, F and Obotiba, AD and Meertens, R and Alshalawi, O and Mokbel, K and Strain, WD and Knapp, KM},
title = {Assessment of Bone Mineral Density, Total Body Composition and Joint Integrity in Long COVID: A 12-Month Longitudinal Feasibility Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
pmid = {41375862},
issn = {2077-0383},
support = {a PhD scholarship from Qassim University, Saudi Arabia.//Qassim University/ ; },
abstract = {Background/Objectives: A subset of individuals develops persistent symptoms following SARS-CoV-2 infection, including musculoskeletal (MSK) manifestations, a condition known as long COVID (LC). Emerging hypotheses suggest that chronic low-grade inflammation in LC may impair bone metabolism and compromise joint health. However, empirical evidence is limited, and the impact of LC on MSK health, particularly bone and joint integrity, is poorly understood. To determine the influence of LC on MSK function, including bone health, body composition, and joint integrity. Methods: A 12-month longitudinal prospective cohort feasibility study was conducted involving 45 adults with LC and 40 well-recovered (WR) post-COVID-19 controls. Baseline and follow-up assessments included dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD) and total body composition (TBC), alongside ultrasound of the hand and knee joints to evaluate intra-articular changes. Results: The LC group had more fat in the gynoid, android, and leg regions at each assessment point compared to the controls (p < 0.01). LC showed a significantly lower knee synovial hypertrophy at the baseline, 13.3% compared to WR 45% (p = 0.001), and a marginal improvement in hand synovial hypertrophy, over 12 months, from a median of 2 (IQR 1;5) to 1 (IQR 0;3) (p = 0.012), as observed via MSK ultrasound. No notable differences were found between groups regarding BMD, either in the LC group compared to the control group or overtime. Conclusions: This cohort study of LC adults and controls found no evidence of rapid bone loss; however, adiposity and joint symptoms suggest the need for ongoing monitoring. Future research should focus on MSK markers, muscle function, advanced imaging, and improving MSK health.},
}
@article {pmid41373075,
year = {2025},
author = {Jornada Ben, &#xc2; and Varga, AN and de Bruijn, S and Dekker, WB and van den Wijngaard, CC and Verburg, AC and Hoogeboom, TJ and van der Wees, P and Ostelo, RWJG and Bosmans, JE and van Dongen, JM},
title = {A comparison of allied healthcare versus no allied healthcare on participation, fatigue, physical functioning and health-related quality of life for patients with persistent complaints after a COVID-19 infection.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2600139},
pmid = {41373075},
issn = {1365-2060},
mesh = {Humans ; *Quality of Life ; *COVID-19/therapy/psychology/complications/epidemiology ; Female ; Male ; *Fatigue/epidemiology/etiology ; Middle Aged ; Adult ; SARS-CoV-2 ; Aged ; Comorbidity ; Anxiety/epidemiology ; },
abstract = {OBJECTIVE: To assess the effectiveness of allied healthcare versus no allied healthcare.<br><br>MATERIALS AND METHODS: Data from the ParaCOV cohort (allied healthcare, n&#x2009;=&#x2009;1,451) and the LongCOVID cohort (no allied healthcare/control, n&#x2009;=&#x2009;1427) were analyzed. Average treatment effects (ATEs) between groups were estimated using Targeted Maximum Likelihood Estimation adjusted for age, sex, body mass index, smoking status, comorbidities, and effect outcomes' baseline values. A&#x2009;&#x2265;&#x2009;10% between-group difference in improvement from baseline (BTGD) was considered clinically relevant for participation, fatigue, and physical functioning, and &#x2265;0.062 for health-related quality of life.<br><br>RESULTS: Patients receiving allied healthcare were older (49.2 vs. 41.2&#x2009;years), less often female (63.3% vs. 70.1%), had higher BMI (28.2 vs. 26.1), smoked less frequently (5.0% vs. 9.0%), had more comorbidities (49.2% vs. 41.9%), and lower baseline anxiety and depression scores compared to those not receiving allied healthcare. For participation, ATEs after 6 and 12&#x2009;months were respectively -2.62 (95%CI: -4.39; -0.86) and -1.68 (95%CI: -4.81;1.45), with BTGDs of 4.7% and 1.8% favoring the control. For fatigue, ATEs were 1.72 (95%CI: -0.14; 3.58) and 0.97 (95%CI: -1.48; 3.41), with BTGDs of 6.5% and 3.7% favoring the control. For physical functioning, ATEs were 5.75 (95% CI: 4.42; 7.09) and 6.36 (95%CI: 4.84; 7.88), with BTGDs of 1.4% and 2.2% favoring allied healthcare. For health-related quality of life, ATEs were 0.017 (95%CI: -0.008; 0.0044) and 0.033 (95%CI: 0.011; 0.054).<br><br>CONCLUSIONS: Patients with persistent complaints after a COVID-19 infection showed significantly lower participation after 6&#x2009;months, higher health-related quality of life after 12&#x2009;months, and better physical functioning after 6 and 12&#x2009;months of allied healthcare, however, BTGDs were not clinically relevant. Study limitations warrant cautious results interpretation.},
}
@article {pmid41372831,
year = {2025},
author = {Bigogo, G and Audi, A and Ogwel, B and Aol, GO and Ouma, A and Oduor, C and Omondi, D and Komo, T and Nasimiyu, C and Agogo, G and Lo, T and Herman-Roloff, A and Munyua, P and Munywoki, PK},
title = {Risk factors for long COVID among participants of a population-based study in urban and rural Kenya, 2021.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {184},
pmid = {41372831},
issn = {1471-2458},
support = {D43 TW011519/TW/FIC NIH HHS/United States ; },
mesh = {Humans ; Kenya/epidemiology ; *COVID-19/epidemiology/complications ; Male ; Female ; Risk Factors ; Adult ; Middle Aged ; *Rural Population/statistics &amp; numerical data ; *Urban Population/statistics &amp; numerical data ; Adolescent ; Young Adult ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: Post-COVID-19 conditions (PCC) or Long COVID, will linger due to continued circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the burden and risk factors of PCC could guide development of management guidelines for affected persons.<br><br>METHODS: Using Population-Based Infectious Disease Surveillance platforms established in Nairobi and Siaya Counties in Kenya, we followed up participants previously infected with SARS-CoV-2 between 01/05/2020 and 30/09/2021 to evaluate the presence and risk factors for PCC. Interviews were conducted from 13/10/2021 to 22/11/2021 to elicit information on the presence of four primary outcome categories: (i) presence of respiratory symptoms, (ii) self-reported non-recovery after SARS-CoV-2 infection, (iii) psychological distress, and (iv) worsening disability. The latter two were evaluated for persons&#x2009;&#x2265;&#x2009;18 years old. Risk factors assessed included participants' demographic and clinical characteristics. Logistic regression models were developed for each outcome adjusted for household-level clustering.<br><br>RESULTS: Characteristics of the 832 participants from both sites were as follows; 82.7% were <&#x2009;50 years, 59.3% were female, 5/511 (1.0%) were vaccinated with &#x2265;&#x2009;1 dose of COVID vaccine. For the outcomes, 174/832 (20.9%) had respiratory symptoms, 165/793 (20.8%) reported non-recovery following SARS-CoV-2 infection, 152/511 (29.7%) had psychological distress, while 112/511 (21.9%) had a worsening disability. Females had greater odds of reported non-recovery from COVID-19 illness than males, adjusted odds ratio (aOR) of 1.47 (95%CI, 1.01-2.13). Underlying medical conditions was a significant risk factor for all outcomes: for presence of respiratory symptoms, aOR&#x2009;=&#x2009;1.82 (95% CI, 1.16-2.87), for reported non-recovery, aOR&#x2009;=&#x2009;1.93 (95% CI, 1.24-3.02), for psychological distress aOR&#x2009;=&#x2009;1.87 (95%CI, 1.17-2.99), while for worsening disability aOR&#x2009;=&#x2009;2.58 (95% CI, 1.54-4.34). Other significant predictors included living in the Asembo site associated with psychological distress (aOR&#x2009;=&#x2009;2.23; 95% CI, 1.42-3.53), worsening disability (aOR&#x2009;=&#x2009;2.38; 95% CI, 1.43-3.97), and presence of respiratory illness (aOR&#x2009;=&#x2009;2.44; 95% CI, 1.67-3.56).<br><br>CONCLUSION: PCC were found in approximately one-fifth to one-third of participants with the presence of underlying medical conditions being a common risk factor in all outcomes. Advocacy for the prioritization of interventions such as vaccination of persons with underlying medical conditions could consequently result in a reduction in the risk of PCC.},
}
@article {pmid41372813,
year = {2025},
author = {Whitcomb, LA and Berry, K and LaVergne, SM and Natter, N and Baxter, BA and Rao, S and Tipton, M and Gritsenko, MA and Weitz, KK and Gerbasi, V and Bramer, LM and Piehowski, PD and Webb, TL and Henao-Tamayo, M and Chicco, AJ and Dunn, J and Dutt, TS and Ryan, EP},
title = {Blood pro-thrombotic analytes and platelet activation are associated with post-acute sequelae of COVID-19.},
journal = {BMC infectious diseases},
volume = {26},
number = {1},
pages = {61},
pmid = {41372813},
issn = {1471-2334},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Biomarkers/blood ; Longitudinal Studies ; *Platelet Activation ; *Post-Acute COVID-19 Syndrome/blood/complications/immunology ; Proteomics ; *Thrombosis/blood ; },
abstract = {Post-Acute Sequelae of COVID-19 (PASC), or "long COVID," describes persistent symptoms following recovery from SARS-CoV-2 infection. Early identification of circulating biomarkers predictive of PASC is critical for prognosis and therapeutic development yet remains poorly defined. To address this gap, we conducted a longitudinal, multi-omics analysis of blood samples from COVID-19 patients (n = 75), stratified by acute disease severity and PASC status. We integrated targeted multiplex assays, untargeted proteomics (LC-MS), and whole blood flow cytometry to define immune and vascular signatures associated with PASC. We found that individuals who went on to develop PASC exhibited a distinct phenotypic signature between 1 and 35 days post-infection, such as significantly elevated plasma Factor-IX, Tissue factor, and tPA, which reflected hyperactivation of immunothrombotic pathways. Similarly, pathway enrichment analysis revealed ongoing neutrophil degranulation, platelet activation, and extracellular matrix remodeling-indicating unresolved inflammation and immunothrombosis which persisted beyond 77 days post-symptom onset. Unlike prior studies using single biomarkers or limited timepoints, our study offers a comprehensive longitudinal analysis combining proteomic and cellular data to define a durable immune-vascular signature specific to PASC. This integrative approach reveals insights into PASC pathogenesis and highlights candidate biomarkers with potential utility in early risk stratification. Our findings underscore the critical role of chronic immune and endothelial dysfunction in long COVID and point toward actionable targets for intervention. This investigation links biorepository human samples with clinical symptoms and lays the foundation for precision diagnostics and therapeutic strategies aimed at improving long-term outcomes in COVID-19 survivors (NCT04603677).},
}
@article {pmid41372563,
year = {2025},
author = {Humer, B and Berentschot, JC and van Helden-Meeuwsen, CG and Bek, LM and de Bie, M and Defesche, TM and Boly, CA and Drost, M and Hellemons, ME and Dik, WA and Versnel, MA},
title = {Exaggerated IFN-I Response in Long COVID PBMCs Following Exposure to Viral Mimics.},
journal = {Journal of clinical immunology},
volume = {46},
number = {1},
pages = {5},
pmid = {41372563},
issn = {1573-2592},
mesh = {Humans ; *COVID-19/immunology ; *Leukocytes, Mononuclear/immunology ; *Interferon Type I/metabolism/immunology ; *SARS-CoV-2/immunology ; Male ; Female ; Middle Aged ; Adult ; Aged ; },
abstract = {PURPOSE: Long COVID (LC) is a long-term debilitating disease of which the exact pathophysiology is unknown. A dysregulated immune response resulting in hyperresponsive immune cells is hypothesized as a key mechanism in the development of LC. Several studies suggest that acute infections can leave lasting epigenetic changes, which result in heightened immune reactivity. Upon stimulation, these primed immune cells may exhibit exaggerated responses. This form of epigenetic memory can contribute to altered immune dynamics, particularly in response to induction of type I Interferons (IFN-I) pathway activation using a viral mimic. Therefore, we investigated if LC patients exhibit a hyperresponsive response towards viral mimics in comparison with healthy controls (HC).<br><br>METHODS: PBMCs of two distinct LC cohorts, characterized by a different disease course and duration, were collected and transfected using Lyovec with the cGAS and RIG-I agonists G3-YSD and 3p-RNA followed by measurement of IFN-I bioactivity with a reporter cell line.<br><br>RESULTS: Transfection of PBMCs of LC patients with the cGAS and RIG-I agonists resulted in increased IFN-I bioactivity in comparison with HC. Unsupervised hierarchical clustering revealed two distinct clusters, each predominantly composed of either patients or HC. In addition, a moderate correlation between RIG-I stimulation with 3p-RNA and fatigue severity scores was found.<br><br>CONCLUSION: These data show a hyperresponsive phenotype of immune cells of LC patients upon stimulation with viral mimics. The current availability of biologicals and small molecule inhibitors that interfere with aberrant IFN-I pathway activation underscores the importance of pursuing future investigations into this phenomenon.},
}
@article {pmid41370476,
year = {2025},
author = {Szwarcwald, CL and Malta, DC and Almeida, WDS and Souza Júnior, PRB and Damacena, GN and Gomes, CS and Castilho, EA},
title = {Inequities in COVID-19 morbidity in Brazil: the influence of demographic and socioeconomic characteristics and preexisting health conditions.},
journal = {Revista brasileira de epidemiologia = Brazilian journal of epidemiology},
volume = {28},
number = {},
pages = {e250056},
pmid = {41370476},
issn = {1980-5497},
mesh = {Humans ; *COVID-19/epidemiology ; Brazil/epidemiology ; Female ; Male ; Adult ; Cross-Sectional Studies ; Middle Aged ; Socioeconomic Factors ; Young Adult ; Adolescent ; Sociodemographic Factors ; Aged ; Prevalence ; *Health Status Disparities ; },
abstract = {OBJECTIVE: To analyze COVID-19 morbidity according to sociodemographic characteristics and preexisting health conditions, based on data from a survey conducted in 2023 online called "ConVid-2 Behavior Survey".<br><br>METHODS: This was a cross-sectional epidemiological study using the Respondent-Driven Sampling (RDS) method. Prevalence estimates and 95% confidence intervals were calculated for five COVID-19-related indicators. Logistic regression models were applied to test the hypothesis of associations between outcomes and sociodemographic characteristics.<br><br>RESULTS: The sample included 3,805 individuals aged 18 years or older. Approximately 50% of participants had received four or more doses of the COVID-19 vaccine. The estimated prevalence of COVID-19 was 49.5%, with significant and increasing gradients by age and decreasing gradients by education level. Long COVID was identified in 32% of individuals with confirmed COVID-19, with the highest proportions among women (38.3%; OR=0.52; p=0.002), those with financial difficulties (38.9%; OR=1.68; p=0.02), and those with a chronic noncommunicable disease (36.3%; OR=1.58; p=0.03). The highest rate of hospitalization occurred among those with Long COVID (12.7%). Death of a household member due to COVID-19 was reported by 5.1% of participants.<br><br>CONCLUSION: The findings revealed major socioeconomic inequalities across all indicators related to COVID-19 morbidity. Older age, preexisting health conditions, and Long COVID contributed to greater disease severity and increased hospitalization. These findings are relevant to inform public policies aimed at supporting the diagnosis and management of COVID-19-related complications within the public health system.},
}
@article {pmid41369621,
year = {2026},
author = {Keller, C and Mascarenhas, L and Reyes, JL and Duval, S and Benditt, DG},
title = {Association of Autonomic Dysfunction With Long COVID: Evaluation Using Quantitative Autonomic Testing.},
journal = {Journal of the American College of Cardiology},
volume = {87},
number = {2},
pages = {216-230},
doi = {10.1016/j.jacc.2025.09.1608},
pmid = {41369621},
issn = {1558-3597},
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/complications/diagnosis ; Middle Aged ; *Autonomic Nervous System Diseases/physiopathology/diagnosis/etiology ; Adult ; Heart Rate/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Valsalva Maneuver/physiology ; Tilt-Table Test/methods ; Blood Pressure/physiology ; Aged ; *Autonomic Nervous System/physiopathology ; Respiratory Sinus Arrhythmia/physiology ; },
abstract = {BACKGROUND: Persistent symptoms (eg, heart palpitations, lightheadedness, fatigue) despite resolution of acute COVID-19 infection is termed "long COVID syndrome" or simply "long COVID." Long COVID is believed to be associated with autonomic dysfunction, but the nature and severity of any autonomic disturbances are not well understood.<br><br>OBJECTIVES: This study sought to compare autonomic function measures in patients with long COVID, control subjects, and individuals with pure autonomic failure.<br><br>METHODS: Patients referred for autonomic testing were classified into 3 groups: long COVID (acute COVID-19 infection &#x2265;12 weeks before testing), control subjects (COVID-19 negative, normal autonomic tests), and pure autonomic failure (COVID-19 negative, abnormal autonomic testing). Heart rate and blood pressure were recorded during active standing, Valsalva maneuver, respiratory sinus arrhythmia, and tilt-table testing.<br><br>RESULTS: Compared with control subjects, patients with long COVID exhibited both a greater heart rate increase and blood pressure drop with active standing and tilt-table testing (all P < 0.05). They also had lower Valsalva ratios and respiratory sinus arrhythmia values than did control subjects (both P < 0.05). Compared with pure autonomic failure patients, patients with long COVID had a greater heart rate increase but a lower drop in blood pressure with active standing and tilt-table testing and lesser respiratory sinus arrhythmia values and Valsalva ratios (all P < 0.001). After age and sex adjustment, autonomic dysfunction measures in patients with long COVID were comparable with those in the pure autonomic failure group. Further, autonomic testing abnormalities were observed in patients referred up to 40 months after infection.<br><br>CONCLUSIONS: When adjusted for age and sex, patients with long COVID may demonstrate persistent autonomic dysfunction that is similar to patients with pure autonomic failure.},
}
@article {pmid41368891,
year = {2025},
author = {Pinero, S and Li, X and Zhang, J and Winter, M and Lee, SH and Nguyen, T and Liu, L and Li, J and Le, TD},
title = {Omics-based computational approaches for biomarker identification, prediction, and treatment of Long COVID.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/10408363.2025.2583083},
pmid = {41368891},
issn = {1549-781X},
abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), is a major global health problem, with cumulative estimates suggesting that around 400 million people worldwide have been affected. It is characterized by persistent or new symptoms such as fatigue, cognitive impairment, and breathlessness lasting beyond four weeks after acute infection. Diverse clinical manifestations, chronic course, and incompletely understood pathophysiology-including hypotheses involving viral persistence, immune dysregulation, autoimmunity, endothelial dysfunction, and metabolic reprogramming-impede the development of diagnostic criteria, biomarkers, and targeted therapies. We conducted a critical review of 101 Long COVID omics studies, focusing on the computational methods used and their methodological quality. Using standardized criteria, we evaluated study design, statistical rigor, reproducibility, and clinical relevance across genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multiomics integration, and mapped these findings onto regulatory and translational frameworks. Despite substantial methodological heterogeneity, convergent biological signals emerged. Genomic studies implicate risk loci in immune and cardiopulmonary pathways. Epigenomic analyses identify differentially methylated regions in immune and circadian genes. Transcriptomic studies reveal persistent dysregulation of innate immune and coagulation pathways, as well as reproducible molecular endotypes. Proteomic studies consistently show abnormalities in the complement cascade and coagulation, with a small panel of complement proteins showing highly reproducible changes across independent cohorts. Metabolomic studies demonstrate sustained mitochondrial dysfunction and altered cellular bioenergetics for up to two years after infection. Multiomics integration supports at least two major endotypes, characterized by predominant inflammatory versus metabolic dysregulation, and provides a basis for patient stratification and computational treatment discovery. Machine learning models frequently achieve high classification performance, but are rarely externally validated. Critical limitations restrict clinical translation. Most studies are underpowered relative to analytical complexity, use heterogeneous case definitions and controls, and report platform-specific signatures with limited overlap. External validation, preregistered analysis plans, and regulatory-aligned assay development are uncommon. To date, no regulatory-approved diagnostic assay or evidence-based therapeutic intervention has directly emerged from these computational findings. Future progress requires harmonized phenotyping protocols, adequately powered longitudinal cohorts with external validation, integration of spatial omics and explainable artificial intelligence, and early engagement with regulatory and health-technology assessment pathways. This review provides a critical assessment and a translational roadmap, outlining how methodologically robust computational omics can be advanced toward clinically actionable tools for Long COVID.},
}
@article {pmid41368314,
year = {2025},
author = {Mkhabela, K and Van Staden, M and Chetty, YY},
title = {The long-term effects of COVID-19 on oxygen carrying capacity in adults at the University of Limpopo, South Africa.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1636141},
pmid = {41368314},
issn = {2296-858X},
abstract = {BACKGROUND: Long-COVID is a condition characterized by persistent symptoms that last past the acute phase of COVID-19. The symptoms manifest from COVID-19 infection, and include shortness of breath, fatigue, and headaches. These symptoms could be caused by hypoxia and hypoxemia which may result from low haematocrit and hemoglobin. The SARS-CoV-2 virus causes destruction to the heme group of hemoglobin leading to haemolysis, which may lead to disrupted oxygen-carrying capacity.<br><br>AIM: The aim of the study was to investigate the long-term effects of COVID-19 on hemoglobin (Hb) and haematocrit (Hct) in adults.<br><br>METHODOLOGY: This was a case-control cross-sectional study that included a COVID-19 non-naive group (n = 28) and a COVID-19 na&#xef;ve group (n = 196). Questionnaires were administered to participants, and blood levels of Hb and Hct were measured. Furthermore, a food frequency questionnaire (FFQ) was administered to determine the daily intake of iron, folic acid, and vitamin B12 to observe if the diet might have had an influence on Hb and Hct.<br><br>RESULTS: The results show a trend for a low Hct is common in females who had a history of a positive COVID-19 test, and the trend for a normal Hb is prominent across the study population. Results also show a statistically significant (p = 0.001; 95% CI -1.064 to 9.295) intake of vitamin B12 in COVID-19 non-naive males, who also showed to have the highest levels of Hb and Hct (mean of 45.86 g/dl and 15.57% respectively) as compared to other groups.<br><br>CONCLUSION: COVID-19 patients in this study experienced persistent symptoms, but most of the participants had no symptoms at the time the study was conducted. Diet might have had an impact on Hb and Hct in the COVID-19 non-naive male population, as it was observed that they had the highest nutrient consumption and the highest concentrations.},
}
@article {pmid41367392,
year = {2025},
author = {Parks, JK and Johnson, BD and Shea, MG and Kim, CH and Johnston, JI and Carlson, A and Schwartz, JC and Wheatley-Guy, CM},
title = {Interrogating pulmonary diffusing capacity in long COVID: insights from DLCO and DLNO testing.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1725263},
pmid = {41367392},
issn = {1664-042X},
abstract = {INTRODUCTION: The lingering respiratory effects of COVID-19, particularly in patients with Long COVID, remain poorly understood, prompting a comprehensive evaluation of lung function in this population.<br><br>METHODS: Simultaneous measurements of diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), chest computed tomography (CT), lung ultrasound and questionnaires were collected in 74 subjects. Participants were categorized into two groups: those that have no lingering symptoms (NS, n = 37) and those still struggling with symptoms after initial infection, the disease known as Long COVID (LC, n = 37).<br><br>RESULTS: DLCO and DLNO were significantly lower in the LC group compared to the NS group (LC vs. NS, DLCO: 25.94 &#xb1; 7.65 vs. 21.71 &#xb1; 6.35 mL/min/mmHg, p = 0.009; DLNO: 148.5 &#xb1; 35.6 vs. 126.6 &#xb1; 32.2 mL/min/mmHg, p = 0.006). Pulmonary capillary blood volume (Vc) was also significantly lower in the LC group (43.38 &#xb1; 13.87, 70.79 &#xb1; 17.77, p = 0.003; LC vs. NS, respectively). Alveolar volume (VA) is significantly lower in the LC group (LC vs. NS, 5.06 &#xb1; 1.17 vs. 5.95 &#xb1; 1.16, p = 0.004). There was no significant difference between groups for surface area of the lungs available for gas exchange by resistance to gas transfer across the alveolar-capillary membrane (DM) between groups (LC vs. NS, 208.63 &#xb1; 97.3, 223.0 &#xb1; 93.47 mL/min/mmHg, p = 0.54). These findings indicate that Vc is the driving factor of decreased DLCO. CT findings and lung ultrasound showed no differences between the two groups for lung fluid (p = 0.525; p = 0.298).<br><br>CONCLUSION: These findings suggest that a lack of volume available for perfusion could be problematic for these patients and as such requires further investigation for clinical management of these patients.},
}
@article {pmid41367065,
year = {2025},
author = {Kamo, R and Miyagami, T and Saita, M and Hara, N and Mine, Y and Nishina, T and Fukui, Y and Harada, Y and Niitsuma, M and Naito, T},
title = {Virtual Pet-Assisted Therapy to Alleviate Symptoms of Long COVID: A Prospective Pilot Interventional Study.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {31},
number = {},
pages = {e950105},
pmid = {41367065},
issn = {1643-3750},
mesh = {Humans ; Female ; *COVID-19/therapy/complications/psychology ; Pilot Projects ; Middle Aged ; Male ; Prospective Studies ; Adult ; *Animal Assisted Therapy/methods ; SARS-CoV-2 ; Animals ; Dogs ; Aged ; Post-Acute COVID-19 Syndrome ; Fatigue/therapy ; },
abstract = {BACKGROUND Post-COVID-19 condition (long COVID) is characterized by persistent symptoms following acute infection. Given the limited efficacy of pharmacologic treatments, there is growing interest in complementary, non-contact interventions. Virtual pet-assisted therapy (VAT), a virtual reality-based adaptation of animal-assisted therapy, may offer a novel strategy for symptom management in this population. MATERIAL AND METHODS A prospective intervention was conducted in the long COVID clinic at Juntendo University Hospital between July and December 2023. Adult patients with long COVID engaged with a virtual dog for 10 minutes prior to their clinical consultation. Twelve symptoms considered potentially responsive to short-term intervention were self-rated on a 10-point scale before and after the session, with scores representing mean values. RESULTS Forty-two participants (median age: 46 years; 71.4% female) were included in the analysis. The mean total symptom score decreased by 7.2%, from 34.6 points before the intervention to 32.1 points after (P=0.004). Fatigue scores decreased by 9.5% (from 6.3 to 5.7, P=0.004), dyspnea decreased by 17% (from 2.3 to 1.9, P=0.038), memory impairment decreased by 13% (from 4.8 to 4.2, P=0.015), and tinnitus decreased by 22% (from 2.3 to 1.8, P=0.012). CONCLUSIONS VAT could be a feasible and well-tolerated intervention worth further investigation as a potential adjunct for alleviating key symptoms of long COVID, particularly those with psychological components. Although this preliminary study is limited by the lack of a control group, it serves as a pilot study that demonstrates the potential of VAT.},
}
@article {pmid41365308,
year = {2026},
author = {James-Pemberton, PH and Kohli, S and Twynham, J and Westlake, AC and Antill, A and Olkhov, RV and Shaw, AM},
title = {Mass-Standardised Differential Antibody Binding to a Spectrum of SARS-CoV-2 Variant Spike Proteins: Wuhan, Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.4/5, BA.2.75 and BA.2.12.1 Variants-Antibody Immunity Endotypes.},
journal = {Immunology},
volume = {177},
number = {4},
pages = {798-809},
pmid = {41365308},
issn = {1365-2567},
support = {//Attomarker Ltd/ ; //Exeter University Alumni/ ; },
mesh = {Humans ; *SARS-CoV-2/immunology ; *Spike Glycoprotein, Coronavirus/immunology ; *Antibodies, Viral/immunology ; *COVID-19/immunology/virology/prevention &amp; control ; COVID-19 Vaccines/immunology ; Female ; Adult ; Middle Aged ; Male ; Vaccination ; Aged ; },
abstract = {A fully mass-standardised quantitative comparative analysis of the differential antibody binding to spike variant proteins to SARS-CoV-2 has been performed for the variants: Wuhan, Alpha, Beta, Gamma, Delta and the Omicron variants BA.1, BA.2.12.1, BA.2.75, BA.4 and BA.5. Evolution of immunity through five patient cohorts (n = 148 in total) was studied including pre-pandemic, first infection, first vaccine, second vaccine and triple-vaccinated cohorts. A population of immunity endotypes has been observed and is classified against a recovery antibody threshold, with concentrations below this threshold being regarded as a 'dropout': U(+) showing protection to all variants; U(±) with single, double, triple and further dropout endotypes; and U(-) with all variant concentrations being under the threshold. The U(+) incidence rises significantly following multiple rounds of vaccination reaching an (n = 41) incidence of 54% (95% CI 39%-68%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection. The U(+) epitopes are targeted preferentially to the S1 region. U(±), with at least one dropout, has an incidence of 42% (95% CI 28%-57%), an immunity gap. Further, a U(-) sub-cohort of the population up to 13% does not make antibodies above the threshold and may not have a sterilising serum leading to persistent virus and a risk of Long COVID.},
}
@article {pmid41362895,
year = {2025},
author = {Kamdem, OL and Guyot, J and Dupre, C and Gouttefarde, P and Vericel, MP and Fanget, M and Nguefeu Nkenfou, C and Hupin, D and Roche, F and Botelho-Nevers, E and Bongue, B},
title = {Management of patients with post Covid-19 condition in France: A qualitative study exploring nurses' contributions to care pathways.},
journal = {Journal of public health research},
volume = {14},
number = {4},
pages = {22799036251390963},
pmid = {41362895},
issn = {2279-9028},
abstract = {OBJECTIVE: To investigate the different contributions made by nurses in the management of patients with post covid-19 condition (PCC) within the French healthcare context.<br><br>METHODS: We conducted a qualitative study among healthcare professionals in France and enrolled 17 nurses from different care sectors, including private practice, hospitals, schools, and research settings. Semi-structured interviews were conducted between October 2022 and June 2023. The inclusion criteria were: "be a nursing professional" and "having taken care of a patient with PCC." A content thematic analysis was carried out using NVIVO software with advanced pattern recognition analysis, applying the French nursing competency framework to categorize findings.<br><br>RESULTS: Five main themes emerged: (i) the diversity of nurses' contributions and responsibilities, (ii) psychological support: an essential nursing contribution, (iii) screening and referral activities for PCC patients, (iv) care coordination and inter-professional collaboration responsibilities, and (v) therapeutic patient education and clinical research participation. Nurses demonstrated expanded competencies in PCC symptom recognition, adapted traditional tasks to meet novel patient needs, and integrated evolving Long Covid knowledge with existing chronic disease management expertise.<br><br>CONCLUSION: The results offer important perspectives for the organization of the healthcare system and for the nursing profession in the management of chronic diseases. An important aspect of our findings concerns the coordination of care pathways, which raises the issue of task delegation to nurses, particularly in a context of healthcare professional shortages.},
}
@article {pmid41362299,
year = {2026},
author = {Ballouz, T and Kerksieck, P and Haile, SR and Dressel, H and Hämmig, O and Bauer, GF and Fehr, JS and Puhan, MA and Menges, D},
title = {Work ability trajectories and sick leave in individuals with post COVID-19 condition: 3-year follow-up of a population-based cohort.},
journal = {The Lancet regional health. Europe},
volume = {61},
number = {},
pages = {101536},
pmid = {41362299},
issn = {2666-7762},
abstract = {BACKGROUND: Data on the longer-term impact of post COVID-19 condition (PCC) on work-related functioning is limited, despite evidence on the persistence of PCC for years after infection. This study aimed to describe changes in work ability and sick leave associated with PCC up to three years post-infection.<br><br>METHODS: We used data from 667 working-age individuals within a prospective population-based cohort following individuals infected with SARS-CoV-2 between August 2020 and January 2021. PCC was determined at 12 months and work ability was assessed biannually. The impact of SARS-CoV-2 on participants' physical and mental work performance and COVID-19 related sick leave were assessed at three years.<br><br>FINDINGS: Participants with protracted COVID-19 related symptoms at 12 months after infection reported persistently lower work ability scores than those without symptoms, with no evidence of a difference in change over time (-0.12 points per year, 95% CI -0.29 to 0.07). Compared to recovered individuals, work ability scores among those with moderate health impairment improved by +0.72 points per year (95% CI -0.04 to 1.46), while trends were similar among those with mild or severe impairment. A higher proportion of participants with PCC reported worsening in physical and mental performance at work than those without PCC. Among those with PCC, 11.5% (9/78) reported taking COVID-19 related sick leave for one month or more, in contrast to 4.0% (13/327) among those without PCC.<br><br>INTERPRETATION: The study highlights the prolonged impact of PCC on work-related functioning and underscores the need for targeted occupational, clinical and social measures for those affected.<br><br>FUNDING: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe.},
}
@article {pmid41362171,
year = {2025},
author = {Chen, J and Wu, Y and Zhang, Z and Shen, M and Zhou, Y and Zhang, H and Zhuang, Z and Wang, S and Wang, D and Xu, L and Lu, Y and Chen, S},
title = {Utilizing the DMN and DAN to Study the Effects of Acupuncture on Patients with Cognitive Impairment in Long COVID: A Pragmatic Randomized Controlled Trial Protocol.},
journal = {Complementary medicine research},
volume = {},
number = {},
pages = {1-11},
pmid = {41362171},
issn = {2504-2106},
abstract = {BACKGROUND: Cognitive impairment is one of the long COVID symptoms that many people experience after Coronavirus Disease 2019 (COVID-19). Many individuals report a decline in cognitive functions, such as reduced memory and brain fog. These symptoms not only directly affect the cognitive functions of the brain but also hinder daily living activities, thereby reducing the quality of life. Moreover, these symptoms are significant risk factors for long-term cognitive decline in the elderly and can have both short-term and long-term effects on brain function. Clinically, acupuncture is widely used to improve cognitive impairment in the elderly. Elucidating the brain network mechanisms underlying acupuncture therapy for long COVID-related cognitive impairment represents an urgently needed research focus. In this study, we employed acupuncture as an intervention to mitigate cognitive decline in long COVID patients and investigate the potential mechanisms by which acupuncture alleviates cognitive impairment.<br><br>METHODS: In this randomized controlled trial, 60 eligible participants are planned to be recruited and randomly assigned in a 1:1 ratio to the acupuncture group and the health education group, which will then receive acupuncture treatment and health education. The acupuncture group will participate in treatment three times per week for a total of 8 weeks. The health education group will receive health education once per week for a total of 8 weeks. The primary assessment index was the Montreal Cognitive Assessment Scale (MoCA), and the secondary assessment indexes included Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Activity of Daily Living Scale (ADL), Auditory Verbal Learning Test-Huashan Version (AVLT-H), and resting-state functional magnetic resonance imaging data. These assessment indicators were all tested in 1 week each before and after the intervention was implemented.<br><br>DISCUSSION: This trial aims to investigate the therapeutic effects of acupuncture on cognitive impairment in patients with long COVID and to further explore the imaging mechanisms by which acupuncture alleviates cognitive dysfunction in these patients.},
}
@article {pmid41361800,
year = {2025},
author = {Reeder, HT and Thaweethai, T and Foulkes, AS},
title = {Penalized regression with negative-unlabeled data: an approach to developing a Long COVID research index.},
journal = {BMC medical research methodology},
volume = {26},
number = {1},
pages = {5},
pmid = {41361800},
issn = {1471-2288},
support = {R01 HL162373/HL/NHLBI NIH HHS/United States ; R01HL162373/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; SARS-CoV-2 ; Logistic Models ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Moderate to severe Long COVID is estimated to impact as many as 10% of SARS-CoV-2 infected individuals, representing a chronic condition with a substantial public health burden. An expansive literature has identified over 200 persistent symptoms associated with a history of SARS-CoV-2 infection; yet, there remains to be a clear consensus on a syndrome definition. Long COVID thus represents a "negative-unlabeled" outcome where those without prior infection must be Long COVID "negative" but those with prior infection have unknown or "unlabeled" Long COVID status. Despite this lack of a gold standard definition or biomarker, developing and evaluating an approach to characterizing Long COVID is a critical first step in future studies of risk and resiliency factors, mechanisms of disease, and interventions for both treatment and prevention.<br><br>METHODS: We recently applied a strategy for defining a numeric Long COVID research index (LCRI) using Lasso-penalized logistic regression, leveraging information on history of SARS-CoV-2 infection as a pseudo-label. In the current manuscript we formalize and evaluate this approach in a simulation framework for the occurrence of infection, Long COVID onset, and symptomatology. We evaluate its performance selecting symptoms associated with Long COVID and distinguishing individuals with Long COVID, in the presence of symptom correlations and demographic confounders. We compare the LCRI method to a simpler index defined by counting Long COVID symptoms, and assess these methods in a reanalysis of data on participants enrolled in the Adult Cohort of the Researching COVID to Enhance Recovery (RECOVER) study.<br><br>RESULTS: Simulation results demonstrate that the Lasso-penalized LCRI methodology appropriately selects symptoms associated with Long COVID, and that the LCRI has high discriminatory power to distinguish Long COVID, outperforming symptom count. This performance was robust to correlation between symptoms, and weighting methods are shown to successfully address potential confounding by demographic characteristics. Analysis of RECOVER data showed the LCRI outperforming symptom count by misclassifying fewer uninfected individuals as having Long COVID.<br><br>CONCLUSIONS: As the LCRI is increasingly used to characterize LC in research settings, this paper represents an important step in understanding its operating characteristics and developing general methodology for settings with negative-unlabeled data.},
}
@article {pmid41361535,
year = {2025},
author = {Marshall, M},
title = {Long-COVID research just got a big funding boost: will it find new treatments?.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41361535},
issn = {1476-4687},
}
@article {pmid41360602,
year = {2026},
author = {De Matteis, S and Consonni, D and Espinosa, A and de Cid, R and Magriña, NB and Castaño-Vinyals, G and Karachaliou, M and Alba Hidalgo, MA and Papantoniou, K and Garcia, J and Kogevinas, M and Straif, K},
title = {Occupational determinants of Long COVID in the population-based COVICAT cohort.},
journal = {Occupational and environmental medicine},
volume = {82},
number = {12},
pages = {579-588},
doi = {10.1136/oemed-2025-110398},
pmid = {41360602},
issn = {1470-7926},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; Middle Aged ; Male ; Adult ; Spain/epidemiology ; Aged ; Risk Factors ; Prospective Studies ; SARS-CoV-2 ; *Occupational Exposure/adverse effects/statistics &amp; numerical data ; Occupations ; *Occupational Diseases/epidemiology ; },
abstract = {OBJECTIVES: Occupational factors affect SARS-CoV-2 infection risk, but the occupational factors associated with Long COVID (LC) are unknown. We aimed to address this issue using individual data in a population-based cohort.<br><br>METHODS: In the prospective COVICAT study, 2020-2023, Catalonia, Spain, we examined the association between occupational determinants and LC. Among subjects with previous SARS-CoV-2 infection, those employed in the pandemic and with occupational information were analysed. Different metrics, including four job-exposure matrices, were used to evaluate individual occupational risk factors for LC (postinfection symptoms &#x2265;3&#x2009;months). Poisson models were used to estimate adjusted risk ratios (RRs) and 95% CIs.<br><br>RESULTS: Among 2054 workers (1308&#x2009;women, 746 men) aged 40-69 years, 486 developed LC (23.7%). Workers in jobs at high COVID-19 risk according to all metrics including health/social care, education, retail, transport and security showed higher LC risk. The main drivers of increased risk were close contact with colleagues and the public (RR up to 1.50; 95% CI 1.18 to 1.91), no social distance at workplace (up to 1.46; 95% CI 1.16 to 1.84), rare or no use of facemask (1.41; 95% CI 1.09 to 1.83) and commute by public transport (1.58; 95% CI 1.20 to 2.08). Working on-site during the pandemic was also associated with a higher LC risk compared with teleworking (1.57; 95% CI 1.19 to 2.09). Individual non-occupational risk factors for LC included female sex, comorbidities, obesity, number and severity of acute infections; vaccination and older age were protective.<br><br>CONCLUSIONS: In a population-based cohort, several occupational factors increased LC risk. Focused preventive strategies are warranted to avoid the associated public health burden. LC should be recognised and compensated as an occupational disease.},
}
@article {pmid41359411,
year = {2025},
author = {Al-Oraibi, A and Martin, CA and Woolf, K and Nellums, LB and Tarrant, C and Pareek, M},
title = {Patterns of long COVID symptoms among healthcare workers in the UK and variations by sociodemographic, clinical and occupational factors: a cross-sectional analysis of a nationwide study (UK-REACH).},
journal = {Journal of the Royal Society of Medicine},
volume = {118},
number = {12},
pages = {387-406},
pmid = {41359411},
issn = {1758-1095},
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Ethnicity/statistics &amp; numerical data ; *Health Personnel/statistics &amp; numerical data ; *Post-Acute COVID-19 Syndrome/epidemiology ; Sociodemographic Factors ; United Kingdom/epidemiology ; },
abstract = {OBJECTIVES: This study aimed to examine symptom patterns between healthcare workers (HCWs) with and without long COVID, identify the most common long COVID symptom groups and investigate how these symptom profiles vary across different ethnic groups, demographic characteristics, clinical factors and occupational roles in UK HCWS.<br><br>DESIGN: We conducted a cross-sectional study using data from the United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH) cohort study. Data were collected electronically between October 2021 and October 2022.<br><br>SETTING: United Kingdom.<br><br>PARTICIPANTS: Individuals aged 16 years or older, residing in the UK, working as HCWs or ancillary workers in a healthcare setting and/or registered with one of seven major UK healthcare professional regulators.<br><br>MAIN OUTCOME MEASURES: Long COVID was defined as symptoms persisting for &#x2a7e;12 weeks following SARS-CoV-2 infection. Our primary outcome was the presence or absence of particular groups of long COVID symptoms. We collapsed 28 symptoms into seven groups: cardiopulmonary, gastrointestinal, musculoskeletal, neurocognitive/neurologic, upper respiratory tract, psychological/social and systemic.<br><br>RESULTS: Among 4033 HCWs with a history of COVID-19, those with long COVID (26.5%; 1067/4033) reported a higher prevalence of systemic, neurological and psychological symptoms compared with those without long COVID. Among those with long COVID, the most commonly reported symptom groups were neurocognitive/neurologic (63.4%), cardiopulmonary (40.0%) - highest among Asian HCWs at 45.6% - and systemic (54.6%), which particularly affected Black and Mixed ethnicities at 64.0% and 63.9%, respectively. In multivariable analyses, Asian HCWs had higher odds of experiencing cardiopulmonary symptoms (adjusted odds ratio (aOR): 1.62, 95% CI 1.04-2.51, p = 0.032), while female HCWs were more likely to experience gastrointestinal (aOR: 3.78, 95% CI 1.14-12.45, p = 0.029) and neurocognitive symptoms (aOR: 1.58, 95% CI 1.10-2.28, p = 0.014). Compared with those in medical roles, musculoskeletal symptoms were more commonly reported by those in nursing (aOR: 2.50, 95% CI 1.32-4.72, p = 0.005), allied health professional (aOR: 1.82, 95% CI 1.01-3.30, p = 0.048) and dental roles (aOR: 3.07, 95% CI 1.31-7.17, p = 0.010). Vaccination with two or three doses was protective against several symptom groups, including cardiopulmonary, musculoskeletal and neurocognitive symptoms.<br><br>CONCLUSIONS: Our findings are the first to reveal distinct patterns in long COVID symptoms among HCWs with significant variations by ethnicity, sex and occupational role. These findings emphasise the need for targeted support strategies and workplace adjustments that consider both occupation-specific risks and individual sociodemographic factors.},
}
@article {pmid41358013,
year = {2025},
author = {Buettikofer, T and Maher, A and Johnson, M and Hartono, S and Rainbird, V and Nickels, M and Bennett, M and Huang, HC and Gaughwin, P and Vandermeide, MA and Carlyle, R and Ho, W and Brady, M and Patterson, K and Morris, J and Mitchell, I and Paratz, J and Freene, N and Bissett, B},
title = {Safety and Physical Outcomes of a Novel Australian Multidisciplinary Long COVID Clinic That Incorporates Exercise: A Prospective Observational Study.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {7827-7838},
pmid = {41358013},
issn = {1178-2390},
abstract = {BACKGROUND: Exercise therapy remains somewhat controversial in those with Long COVID (symptoms lasting >3 months), due to concerns for safety and the potential for harm.<br><br>PURPOSE: This study describes the safety and physical outcomes of an Australian multidisciplinary Long COVID Recovery Clinic that incorporates personalised exercise prescription including respiratory and peripheral muscle strengthening, carefully monitored cardiovascular training and pacing of activity.<br><br>PATIENTS AND METHODS: Prospective observational study of adults (&#x2265;18 years) engaging with a single site Long COVID Recovery Clinic (March 2022 to June 2023). Clinic eligibility required symptoms >12&#xa0;weeks which impaired activities of daily living. Safety was pre-defined as <10% of participants experiencing a minor adverse event, and no serious disability or death as a result of participation in exercise. Physical outcomes included Modified COVID-19 Yorkshire Rehabilitation Scale, changes in exercise capacity (6-minute-walk-test), inspiratory muscle strength (maximum inspiratory pressure), Timed-Up-and-Go and ten-metre-walk-test. Data analysis included repeated measures Multivariate Analysis of Variance (MANOVA) to explore assessment and reassessment measures collectively, and repeated measures t-test.<br><br>RESULTS: Of 207 consumers referred, (62% male, median age 45, range 18-84), 119 (57% of the total referred) enrolled to participate in the program. Of these, 72 (61%) completed the program, median participation duration 112 days (range 5-384). There were no adverse events as a result of participation in exercise. Consumers who completed the program showed improvement in Modified COVID-19 Yorkshire Rehabilitation Scale Other Symptoms (MD -1.5, p=0.003), Overall Health Score (MD1.3, p<0.001), Total Score (MD -6.5, p=0.02); maximum-inspiratory-pressure (MD 11.7 cmH2O, p=0.002); Timed-Up-and-Go (MD -1.0 sec, p<0.001); ten-metre-walk-test comfortable speed (MD 0.7 m/sec, p=0.006) and fast speed (MD 0.2 m/sec, p<0.001); and 6-minute-walk-test distance (MD 63.0 m, p<0.001).<br><br>CONCLUSION: This multidisciplinary therapy program that incorporates exercise was safe and associated with improvements in physical and functional outcomes for participants who completed the program.},
}
@article {pmid41357843,
year = {2025},
author = {Małujło-Balcerska, E and Bączek, K and Górski, W and Kumor-Kisielewska, A and Gwadera, &#x141; and Białas, AJ and Piotrowski, WJ},
title = {Peripheral Levels of Selected Biomarkers in Patients with Post-Sarcoidosis Chronic Fatigue Syndrome.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {16921-16930},
pmid = {41357843},
issn = {1178-7031},
abstract = {INTRODUCTION: Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and multiple symptoms such as cognitive impairment and muscle pain, often linked to immune-inflammatory dysfunction. Sarcoidosis, a granulomatous disease with systemic inflammation, commonly causes fatigue, even during remission. This study examined whether fatigue and depressive symptoms in sarcoidosis remission relate to residual inflammation or oxidative stress. Recent studies highlight parallels between post-infectious fatigue syndromes, including Long COVID, and sarcoidosis-related fatigue, emphasizing IL-6 mediated pathways. Theoretical frameworks of immune-metabolic interactions further support the hypothesis that residual inflammation drives persistent fatigue in remission.<br><br>MATERIALS AND METHODS: Seventy-one sarcoidosis patients were divided into three groups: remission with fatigue (RS/CFS, n=22), remission without fatigue (R/S, n=23), and active sarcoidosis (A/S, n=26). Fatigue was assessed with the Fatigue Assessment Scale (FAS), depressive symptoms with the Beck Depression Inventory (BDI), and quality of life with PHQ-9. Pulmonary function tests measured FEV1 and FVC. Serum biomarkers (hsCRP, IL-6, TNF-&#x3b1;, total antioxidant status, and 8-isoprostanes) were measured by ELISA.<br><br>RESULTS: RS/CFS and A/S groups showed significantly higher fatigue, and depressive scores compared to R/S (P <0.05). HsCRP and IL-6 levels were elevated in fatigued patients (RS/CFS and A/S) versus non-fatigued (R/S) (P <0.05). IL-6 correlated moderately with fatigue and depression scores (r =0.33). No significant differences were found in TNF-&#x3b1; or oxidative stress markers. Pulmonary function was slightly reduced in fatigued patients and weakly correlated with mental fatigue (r = -0.26).<br><br>CONCLUSION: Our data support a role for low-grade systemic inflammation, especially elevated hsCRP and IL-6, in fatigue and depressive symptoms during sarcoidosis remission. Further research integrating inflammatory, oxidative, metabolic, and neuroendocrine pathways is needed to elucidate fatigue pathogenesis and develop targeted interventions. IL-6 may represent a potential biomarker of fatigue in sarcoidosis. These findings highlight the importance of persistent low-grade inflammation and may guide the development of future therapeutic strategies.},
}
@article {pmid41357833,
year = {2025},
author = {Liu, LD and Duricka, DL},
title = {Case Report: Celiac plexus block improves gastrointestinal Long COVID symptoms.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1589809},
pmid = {41357833},
issn = {1662-4548},
abstract = {Lingering symptoms following SARS-CoV-2 infection, recognized as the clinical entity "Long COVID," are common. Gastrointestinal dysfunction during and after COVID have received little attention to date and remain largely unaddressed. We have previously shown that numerous symptoms of Long COVID excluding gastrointestinal symptoms improve or resolve following stellate ganglion blocks (SGB). Here, we are first to report successful treatment of persistent post-COVID epigastric pain and diarrhea in three patients using celiac plexus block, a procedure commonly used for visceral abdominal pain and implicating the autonomic nervous system in Long COVID-associated GI symptoms.},
}
@article {pmid41357333,
year = {2025},
author = {Wu, CY and Reynolds, WC and Abril, I and McManus, AJ and Brenner, C and González-Irizarry, G and Gutiérrez-Martínez, L and Sun, O and Rosand, J and Tanzi, RE and Arnold, SE and Guzmán-Vélez, E},
title = {Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial.},
journal = {EClinicalMedicine},
volume = {89},
number = {},
pages = {103633},
pmid = {41357333},
issn = {2589-5370},
abstract = {BACKGROUND: Long-COVID often involves cognitive difficulties, immune dysregulation, and mitochondrial dysfunction. Studies suggest nicotinamide adenine dinucleotide (NAD+) precursors like nicotinamide riboside (NR) may reduce inflammation and support mitochondrial and neurological function. This double-blind, placebo (PBO)-controlled clinical trial with a placebo lead-in phase evaluated the effects of NR (2000 mg/day) on NAD+ and changes in cognitive and long-COVID symptoms.<br><br>METHODS: This was a 24-week, double-blind, placebo-controlled trial at a single center in Boston, USA, between August 2021 and September 2023. 58 community-dwelling participants with long-COVID were randomized 2:1 to the NR-NR group (NR for 20 weeks) or the PBO-NR group (PBO for 10 weeks, followed by NR for 10 weeks). The primary outcome was cognition, assessed using the Everyday Cognition scale (ECog), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and Trail Making Test-B (TMT-B). Secondary outcomes included the Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Pittsburgh Sleep Quality Index. We conducted a mixed model for repeated measures to compare groups, then post-hoc and unadjusted for multiplicity, combined both groups to explore changes from baseline after 10 weeks of NR. This trial was registered with ClinicalTrials.gov (NCT04809974) in 2021.<br><br>FINDINGS: 37 participants (64%) were assigned to NR-NR, and 21 participants (36%) to PBO-NR. There was a 32.4% and 51.4% dropout in the NR-NR group at 10 weeks and 20 weeks, respectively, vs. 14.3% dropout at each timepoint in the PBO-NR group. In the NR-NR group, NAD+ levels increased by 2.6- to 3.1-fold after 5-10 weeks of supplementation, respectively, and remained elevated at 20 weeks. In the PBO-NR group, NAD+ levels remained close to baseline (0.93- to 1.0-fold change, 95% CI: 0.5-1.4) during the initial 5 and 10 weeks of PBO. After switching to NR, levels rose to a 2.6-fold and 2.1-fold increase after 5 and 10 weeks of NR, respectively. No significant between-group differences were observed for cognitive outcomes (ECog, RBANS, TMT-B; p-values = 0.47-0.74). There were no significant differences in fatigue severity (p = 0.59), sleep quality p = 0.69), and symptoms of anxiety (p = 0.84) or depression (p = 0.20) between PBO and NR groups. In post-hoc exploratory analysis, examining within-group changes during 5 and 10 weeks of NR intake by grouping all participants during the first 10 weeks of the NR phase, there were significant differences from baseline after 10 weeks of NR in executive functioning, fatigue severity, sleep quality, and symptoms of depression (compared with no significant changes in TMT-B, FSS, PSQI, BAI, or BDI scores during the PBO phase). One serious adverse event was reported, deemed unrelated to the study drug or trial.<br><br>INTERPRETATION: In long-COVID, NR increased NAD+ within 5 weeks but did not significantly improve cognition, fatigue, sleep, or mood vs. PBO. Exploratory analyses suggested within-group benefits after 10 weeks of NR, supporting the need for larger trials.<br><br>FUNDING: This work was supported by Niagen Bioscience, the MGH McCance Center for Brain Health, Lavine Brain Health Innovation Fund, MGH ECOR CDI Physician-Scientist Development Award, and the Alzheimer's Association (grant no. AARGD-23-114103).},
}
@article {pmid41357034,
year = {2025},
author = {Baratta, JM and Jensen, KA and Cobb, C},
title = {Exploring the Effects of Pemivibart Monoclonal Antibody Infusion in Long COVID: A Case Series Offering Initial Clinical Insights.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {e96246},
pmid = {41357034},
issn = {2168-8184},
abstract = {Long COVID, or post-COVID conditions (PCC), affects a substantial proportion of adults and is characterized by persistent symptoms such as fatigue, postexertional malaise (PEM), cognitive dysfunction, and dysautonomia. At present, no Food and Drug Administration-approved therapies exist. Pemivibart (Pemgarda), a monoclonal antibody (mAb) authorized under Emergency Use Authorization (EUA) for preexposure prophylaxis in immunocompromised individuals, has not been studied for PCC but may theoretically facilitate clearance of viral antigens. We report three individuals with longstanding, debilitating PCC who received pemivibart infusion under EUA. Each experienced rapid symptomatic improvement, most notably in fatigue with PEM, dysautonomia, and cognitive dysfunction. One patient achieved resolution of her most limiting symptoms within a week and sustained functional recovery following repeat infusion. Another demonstrated significant gains across several symptom domains and was able to resume prior physical activities, although benefits waned after two to three weeks. A third with autoimmune comorbidities reported dramatic improvement in energy and cognition, and continued to feel well at six weeks. The rationale for this case series stems from emerging hypotheses that persistent viral antigens may contribute to the pathophysiology of Long COVID and that neutralizing antibodies could facilitate antigen clearance and symptom resolution. In the three cases, pemivibart infusion was temporally associated with rapid and meaningful improvement in fatigue associated with PEM, cognitive dysfunction, and dysautonomia, symptom clusters that often drive functional impairment in PCC. While the magnitude and duration of benefit varied among individuals, the consistent pattern of improvement supports further exploration of mAb therapy as a potential disease-modifying approach. These preliminary findings highlight the need for controlled, biomarker-guided studies to determine efficacy, durability, and patient subgroups most likely to respond. Pemivibart remains authorized only for preexposure prophylaxis in immunocompromised individuals and is not approved for the treatment of PCC.},
}
@article {pmid41354797,
year = {2025},
author = {Tanaka, S and Williams, S and Zhang, L and Yi, N and Garvey, WT and Cherrington, AL and Howell, CR},
title = {Persistent poverty, glycemic control and adverse COVID-19 outcomes: a retrospective study using real-world data.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {159},
pmid = {41354797},
issn = {1471-2458},
support = {P30 CA006927/CA/NCI NIH HHS/United States ; U54 MD008176/MD/NIMHD NIH HHS/United States ; U54MD008176//NIH NIMHD/ ; 931540//American Heart Association/ ; },
mesh = {Humans ; *COVID-19/epidemiology/mortality ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Poverty/statistics &amp; numerical data ; *Glycemic Control/statistics &amp; numerical data ; Aged ; Adult ; Hospitalization/statistics &amp; numerical data ; *Diabetes Mellitus/epidemiology ; Glycated Hemoglobin/analysis ; *Poverty Areas ; Risk Factors ; Residence Characteristics/statistics &amp; numerical data ; SARS-CoV-2 ; },
abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the profound impact of diabetes and neighborhood environments on health outcomes. Persistent poverty areas, characterized by long-standing economic deprivation, may contribute to increased risk for severe COVID-19 outcomes, particularly among individuals with poor glycemic control. This study investigated the associations between persistent poverty, longitudinal glycemic control by diabetes status, and adverse COVID-19 outcomes using real world data.<br><br>METHODS: We conducted a retrospective analysis using electronic health record (EHR) data from a large Academic health system. The sample included 3,681 adults diagnosed with COVID-19 between March 2020 and January 2021, with available HbA1c and neighborhood level data. Residence in census-tract level persistent poverty areas was categorized as yes vs. no while diabetes status and glycemic control were categorized into five groups based on history of diagnosis and HbA1c measured up to three years prior to infection. Bayesian multivariable logistic regression models assessed independent and multiplicative associations between living in a persistent poverty census tract, glycemic control by diabetes status, and adverse COVID-19 outcomes [e.g. hospitalization, intensive care unit (ICU) admission, and death during hospitalization], controlling for demographics and other social risk factors.<br><br>RESULTS: Among 3,681 patients (mean age 54 years; 60% female; 47% Black), 41.4% were hospitalized, 19.2% were admitted to the ICU, and 6.2% died. Overall, 18.0% resided in persistent poverty areas, 36.2% had diabetes [16.6% undiagnosed diabetes, and 11.1% poorly controlled T2DM]. Residing in persistent poverty areas was associated with an increased risk of hospitalization (OR 1.28, 95% CI: 1.02-1.61), ICU admission (OR 1.40, 95% CI: 1.08-1.80), and mortality (OR 1.50, 95% CI: 1.01-2.22). Patients with undiagnosed diabetes had an increased risk of hospitalization (OR 3.05, 95% CI 2.41-3.86) and mortality (OR 1.96, 95% CI: 1.30-2.97).<br><br>CONCLUSION: This study highlights that residing in a persistent poverty census tract as well as poor glycemic control independently contribute to COVID-19 outcomes. Ongoing management of glycemic control and early preventive strategies in persistent poverty areas may mitigate adverse outcomes in COVID-19 infection and subsequent sequalae like Long COVID.},
}
@article {pmid41354206,
year = {2026},
author = {Jiang, Z and Shan, T and Li, Y and Han, F and Feng, B and Zhen, X and Ma, J and Ni, H and Peng, J and Xu, M},
title = {Persistent attenuation of lymphocyte subsets after mass SARS-CoV-2 infection.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {163},
number = {},
pages = {108287},
doi = {10.1016/j.ijid.2025.108287},
pmid = {41354206},
issn = {1878-3511},
mesh = {Humans ; *COVID-19/immunology ; Male ; Female ; Middle Aged ; *Lymphocyte Subsets/immunology ; Aged ; SARS-CoV-2/immunology ; Adult ; CD8-Positive T-Lymphocytes/immunology ; Lymphopenia/immunology ; CD4-CD8 Ratio ; Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; Cardiovascular Diseases/immunology ; Young Adult ; Aged, 80 and over ; },
abstract = {OBJECTIVES: Growing evidence suggests that lymphocyte subsets are declined in COVID-19 patients, but it is unclear if these alterations persist after widespread exposure to SARS-CoV-2 or how long they last.<br><br>METHODS: We analyzed lymphocyte subset data from 40,537 patients across three phases: pre-COVID, mass infection, and post-COVID. The counts of lymphocyte subsets and CD4[+]/CD8[+] ratios were compared using Mann-Whitney U test or Kruskal-Wallis H test. Monthly post-exposure data were compared with pre-exposure data to assess the persistence of impact on lymphocyte subsets by SARS-CoV-2, and subgroup analyses were performed in patients with cardiovascular disease.<br><br>RESULTS: During mass infection, T cells, CD4[+]T cells, CD8[+]T cells, NK cells, and B cells dropped significantly. Even 20 months post-infection, CD8[+] T cells remained 9.9% below baseline. Baseline lymphocyte subsets differed significantly by sex and age. Immune recovery varied by age and sex, with older adults and males showing prolonged lymphopenia. In cardiovascular disease patients, T lymphocytes remained 72.9% below baseline for 20 months post-infection.<br><br>CONCLUSION: Our findings redefine SARS-CoV-2 infection as a condition of long-lasting immune compromise. The sustained subnormal lymphocytes-particularly in cardiovascular disease cohorts-highlight a key immunologic feature of long COVID and underscore the need for personalized care.},
}
@article {pmid41351342,
year = {2025},
author = {Winkel, AMAM and de Jonghe, BA and Lap, CR and Haverkort, ME and Sluiter-Post, JGC and Euser, SM and Eggink, D and Geerlings, SE and Tami, A and de Jong, MD and van Lelyveld, SFL and van Houten, MA},
title = {Persistent Symptoms in SARS-CoV-2-Infected and Non-Infected Household Members: A Prospective Cohort Study.},
journal = {Journal of medical virology},
volume = {97},
number = {12},
pages = {e70727},
pmid = {41351342},
issn = {1096-9071},
support = {//The SARSLIVA 1 study was supported by internal funds from the National Institute for Public Health and the Environment (RIVM), and by the Netherlands Organisation for Health Research and Development (ZonMw), grant number 10430012010017, financed in part by the Netherlands Ministry of Health, Welfare and Sport./ ; },
mesh = {Humans ; *COVID-19/epidemiology/psychology/diagnosis ; Adult ; Prospective Studies ; Male ; Female ; Middle Aged ; Quality of Life ; Child ; Adolescent ; *SARS-CoV-2/isolation &amp; purification ; Young Adult ; Anxiety/epidemiology ; Netherlands/epidemiology ; Depression/epidemiology ; Family Characteristics ; Prevalence ; Fatigue/epidemiology ; Surveys and Questionnaires ; Saliva/virology ; },
abstract = {This prospective study assessed the prevalence, type, and consequences of persistent symptoms following a nonhospitalized SARS-CoV-2 infection by comparing infected and noninfected children and adults of Dutch households. Two comparable prospective household studies were conducted during two pandemic phases. At baseline, all household members were tested for SARS-CoV-2 with 10 consecutive saliva samples during a 6-week period using RT-PCR. Questionnaires assessing persistent symptoms, health-related quality of life (HRQoL), anxiety, and depressive symptoms were collected at 6 and 12 months. Of the 297 included participants (median age 34 years, IQR 12-48), 201 (67.7%) tested positive for SARS-CoV-2. At 6 months, only one child reported persistent symptoms. SARS-CoV-2-infected adults (> 18 years) reported more pulmonary symptoms (15.2% vs. 3.4%, p = 0.023), and tended to report more fatigue (12.8% vs. 3.4%, p = 0.061) and exertion-related symptoms (8.8% vs. 1.7%, p = 0.107) compared to the negative adults. Adult participants with persistent symptoms reported decreased HRQoL and increased anxiety and depressive symptoms. This study found that SARS-CoV-2-positive adults tended to have higher prevalence of respiratory symptoms, fatigue, and exertion-related symptoms 6 months after SARS-CoV-2 infection, whereas children rarely reported persistent symptoms. Persistent symptoms were associated with a reduced HRQoL and increased anxiety and depression.},
}
@article {pmid41350176,
year = {2026},
author = {Miller, CM and Moen, JK and Iwasaki, A},
title = {The lingering shadow of epidemics: post-acute sequelae across history.},
journal = {Trends in immunology},
volume = {47},
number = {1},
pages = {9-18},
doi = {10.1016/j.it.2025.10.010},
pmid = {41350176},
issn = {1471-4981},
mesh = {Humans ; *COVID-19/epidemiology/complications/immunology ; Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Epidemics ; *Fatigue Syndrome, Chronic/epidemiology/etiology ; Host-Pathogen Interactions/immunology ; Chronic Disease ; Lyme Disease ; },
abstract = {The SARS-CoV-2 pandemic has drawn global attention to post-acute infection syndromes (PAIS), with millions affected by post-acute sequelae of COVID-19 (PASC, or Long COVID). While Long COVID is newly defined, PAIS have been described for over a century following epidemic infections. Multiple pathogens - including influenza, Epstein-Barr virus, and Borrelia burgdorferi, among others - can precipitate persistent, poorly understood symptoms. Chronic illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long been linked to infectious triggers. This recurring association highlights critical knowledge gaps and underscores the need for systematic investigation. Unlike prior pandemics, the current era offers advanced technologies and analytic tools to address these gaps. Defining the biology of Long COVID may yield broader insights into host-pathogen interactions and mechanisms of chronic illness.},
}
@article {pmid41349462,
year = {2026},
author = {Eksteen, C and Asja, LC and Rass, A and Riedemann, J and Engelbrecht, AM},
title = {Post COVID-19 pandemic Inflammatory Insights into Cancer: Consequences for immunotherapy.},
journal = {Cytokine &amp; growth factor reviews},
volume = {87},
number = {},
pages = {10-18},
doi = {10.1016/j.cytogfr.2025.12.002},
pmid = {41349462},
issn = {1879-0305},
mesh = {Humans ; *COVID-19/immunology/complications ; *Neoplasms/immunology/therapy/pathology ; *Immunotherapy/methods ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; *Inflammation/immunology ; Cytokine Release Syndrome/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Cytokines/immunology ; Pandemics ; },
abstract = {The COVID-19 pandemic has reshaped the landscape of global health, revealing novel interactions between infectious diseases and chronic conditions such as cancer. Beyond acute infection, growing evidence suggests that persistent exposure to SARS-CoV-2 spike protein, whether through infection or vaccination, may sustain inflammatory pathways that contribute to tumour progression and immune modulation. This review explores the overlap between post-COVID inflammation, particularly in Long-COVID syndromes and the tumour microenvironment (TME), focusing on key mediators such as IL-6, TNF-α, IL-1β, and NF-κB. We revisit the concept of the cytokine storm in the context of persistent inflammation, spike protein immunogenicity and immune exhaustion, proposing a model in which chronic inflammatory signalling may disrupt tumour immune surveillance, reawaken dormant cancer cells and compromise the efficacy of immunotherapies. Comparative analysis with other cancer types highlights shared pathways of oncogenic inflammation. Lastly, we outline emerging therapeutic strategies to mitigate these effects, including cytokine-targeted interventions and immunomodulatory screening in post-COVID cancer patients. These post-pandemic insights call for urgent translational research to ensure effective and safe cancer immunotherapy in the evolving inflammatory landscape.},
}
@article {pmid41349247,
year = {2025},
author = {Halma, M and Varon, J},
title = {Metabolic modulation as a therapeutic strategy for post-acute vaccination syndrome (PACVS): A review of pathomechanisms and existing therapeutic components.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {193},
number = {},
pages = {118864},
doi = {10.1016/j.biopha.2025.118864},
pmid = {41349247},
issn = {1950-6007},
mesh = {Humans ; *Vaccination/adverse effects ; Oxidative Stress/drug effects ; Mitochondria/metabolism/drug effects ; Animals ; *Energy Metabolism/drug effects ; },
abstract = {Post-Acute Vaccination Syndrome (PACVS) is a post-vaccination disorder marked by persistent fatigue, cognitive impairment, and exercise intolerance. Current research identifies interconnected pathophysiological processes, including persisting spike protein, mitochondrial dysfunction, decreased tissue oxygenation, and impaired metabolism. Emerging treatments rely on metabolic regulation and therapeutic agents promoting mitochondrial and vascular function. These therapies stimulate cellular energy generation, reduce oxidative stress, and regulate inflammatory pathways. This review examines metabolic and mitochondrial mechanisms underlying PACVS, evaluates existing therapeutic strategies targeting these pathways, and synthesizes current evidence for future research and clinical management.},
}
@article {pmid41348962,
year = {2025},
author = {Carrouel, F and Lvovschi, VE and du Sartz de Vigneulles, B and Rhanoui, M and Salamon, R and Lamure, M and Salque, C and Lan, R and Dussart, C},
title = {Prevalence, Risk Factors, Disease-Related Knowledge, and Vaccination Attitudes and Behaviors for Long COVID Among French Civil Servants: Cross-Sectional Survey.},
journal = {JMIR public health and surveillance},
volume = {11},
number = {},
pages = {e83323},
pmid = {41348962},
issn = {2369-2960},
mesh = {Humans ; Cross-Sectional Studies ; France/epidemiology ; *COVID-19/epidemiology/prevention &amp; control/psychology ; Male ; Female ; *Health Knowledge, Attitudes, Practice ; Middle Aged ; Adult ; Risk Factors ; Prevalence ; *COVID-19 Vaccines/administration &amp; dosage ; Surveys and Questionnaires ; *Government Employees/statistics &amp; numerical data/psychology ; *Vaccination/statistics &amp; numerical data/psychology ; Aged ; },
abstract = {BACKGROUND: Long COVID affects millions worldwide, straining health systems and workforce stability. This first nationwide survey among French civil servants combines epidemiological assessment with a Knowledge, Attitudes, and Behaviors approach. Long COVID remains a diagnostic and epidemiological challenge with evolving symptoms and uncertain categorization, particularly among self-suspected cases. Beyond prevalence and risk factors, understanding behavioral dimensions is essential to developing prevention strategies and maintaining workforce resilience.<br><br>OBJECTIVE: This study aimed to (1) assess the prevalence of long COVID among French civil servants; (2) identify associated sociodemographic, occupational, and health-related factors; (3) assess disease-related knowledge of long COVID and (4) examine attitudes and behaviors regarding COVID-19 vaccination.<br><br>METHODS: This cross-sectional survey was conducted in 2024 among active or retired civil servants in France. A Knowledge, Attitudes, and Behaviors-validated questionnaire, based on World Health Organization guidelines, was used. Responses were compared across 4 COVID-19 status groups (no COVID, COVID-19 without long COVID, diagnosed long COVID, and suspected long COVID). Statistical analyses included univariate tests and multivariable logistic regressions to identify factors associated with diagnosed or suspected long COVID.<br><br>RESULTS: Among 3962 eligible respondents, 61 (1.54%; 95% CI 1.20-1.97) reported a formal diagnosis of long COVID and 241 (6.08%; 95% CI 5.38-6.87) without diagnosis. Diagnosed long COVID was significantly associated with long-term sick leave (odds ratio [OR] 1.15, 95% CI 1.03-6.28; P=.04) and long-term illness coverage (OR 0.72, 95% CI 0.27-0.92; P=.03). Suspected long COVID was associated with being in a relationship (OR 1.65, 95% CI 1.08-2.52; P=.02), widowed (OR 2.25, 95% CI 1.18-4.31; P=.01), and uncertain (OR 1.90, 95% CI 1.32-2.74; P<.001) or incomplete COVID-19 vaccination status (OR 1.67, 95% CI 1.16-2.42; P=.01). Knowledge scores differed significantly across groups (ANOVA F3,3476=24.31, P<.001; &#x3c7;&#xb2;6=54.92, P<.001), with diagnosed cases showing the highest proportion of high knowledge (13/61, 21%) compared to 12.4% in the non-COVID group. Among 61 diagnosed cases, 36 (59%; 95% CI 46.4-70.5) were vaccinated, 13 (21%; 95% CI 12.9-33.2) intended to get vaccinated, and 12 (20%; 95% CI 11.6-31.3) remained unvaccinated; among suspected cases, these proportions were 173 (71.8%; 95% CI 65.9-77.1), 30 (12.4%; 95% CI 8.8-17.3), and 38 (15.8%; 95% CI 11.6-21.0), respectively.<br><br>CONCLUSIONS: Unlike previous studies that examined the clinical or behavioral factors separately, this nationwide analysis linked epidemiological data with knowledge and vaccination behaviors. Among French civil servants, long COVID remains underdiagnosed, where absenteeism and sick leave threaten essential services. The study highlights disparities in disease-related knowledge, vaccination attitudes, and behaviors, underlining the importance of workplace health education and systematic screening. Vaccination is associated with lower odds of long COVID, reinforcing its preventive value. Thus, findings reveal organizational implications and support workplace-based prevention strategies integrating vaccination promotion, early detection, and health literacy to sustain the resilience of public services.},
}
@article {pmid41347787,
year = {2025},
author = {Ahmetaj-Shala, B and Peacock, TP and Baillon, L and Swann, OC and Gashaw, H and Rustagi, A and Barclay, WS and Mitchell, JA},
title = {Resistance of endothelial cells to SARS-CoV-2 infection in vitro.},
journal = {Journal of virology},
volume = {99},
number = {12},
pages = {e0120525},
pmid = {41347787},
issn = {1098-5514},
support = {PG/16/83/32467, RG/18/4/33541/BHF_/British Heart Foundation/United Kingdom ; 205100, Studentship, ISSF/WT_/Wellcome Trust/United Kingdom ; Bulbring Award//British Pharmacological Society/ ; BB/R013071/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; BB/R007292/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Humans ; *SARS-CoV-2/physiology ; *Endothelial Cells/virology/metabolism ; *COVID-19/virology/pathology ; Lung/virology ; Angiotensin-Converting Enzyme 2/metabolism/genetics ; Cells, Cultured ; },
abstract = {The secondary thrombotic/vascular clinical syndrome of COVID-19 suggests that SARS-CoV-2 infects the endothelium; however, robust in vitro infection of endothelial cells by various strains of SARS-CoV-2 remains to be demonstrated and continues to be debated. Here, we revisit the question of endothelial cell permissiveness to SARS-CoV-2 using isolated endothelial cells (from the lung, aorta, and endothelial cell progenitors), and additionally, to overcome limitations associated with cultured cells, using native endothelial cells within living precision cut human lung slices and single-cell RNA sequencing to track viral presence. Cellular infection in endothelial monocultures was determined using fluorescence imaging. Mediator release was measured by ELISA, and gene expression was assessed by RT-qPCR. Infection in lung slices was determined using single-cell RNA sequencing, capturing molecular identifiers that aligned to the SARS-CoV-2 viral genome (for lung slices). Each cultured endothelial cell type displayed functional viral responses by increased release of IP-10 when stimulated with Poly-IC (TLR3) or Imiquimod (TLR7/8). Compared to nasal epithelial cells, endothelial cells expressed low or undetectable levels of ACE2 and showed susceptibility to Ebola and Vesicular Stomatitis Virus glycoprotein-expressing pseudoviruses but not live SARS-CoV-2. Importantly, native endothelial cells within human lung slices displayed minimal infectability with SARS-CoV-2. To our knowledge, this is the first study to demonstrate that neither cultured nor native human endothelial cells are particularly, directly permissive to SARS-CoV-2, likely due to the lack of sufficient AEC2 expression. These observations confirm that the vascular inflammation and cardiovascular consequences of COVID-19 are largely an indirect result of paracrine inflammatory responses.IMPORTANCESARS-CoV-2 is recognized not only for its acute effects and links with cardiovascular events but also for its ability to cause long COVID syndrome, which is now a major concern particularly since its long-term implications remain poorly understood. Revisiting endothelial cell permissivity to SARS-CoV-2 is therefore critical in this setting. We show that SARS-CoV-2, and several strains, do not infect cultured different types of endothelial cells cultured alone or native endothelial cells in situ in human lung tissue. Our findings are in line with the idea that vascular inflammation and thrombosis seen in COVID-19 are independent of direct endothelial cell infection and likely to be mediated by factors released by adjacent infected cells or circulating systemic inflammatory mediators. Our work also suggests that where viremia occurs, SARS-CoV-2 passes through the endothelium, facilitated by loss of barrier function because of local inflammation at the site of infection.},
}
@article {pmid41347697,
year = {2025},
author = {Kaptain, RJ and Jensen, KEB and Nielsen, KT and Wæhrens, EE},
title = {Activities of daily living following Long COVID: An exploratory cross-sectional study.},
journal = {Scandinavian journal of occupational therapy},
volume = {32},
number = {1},
pages = {2597212},
doi = {10.1080/11038128.2025.2597212},
pmid = {41347697},
issn = {1651-2014},
mesh = {Humans ; *Activities of Daily Living ; Cross-Sectional Studies ; *COVID-19/rehabilitation/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; Adult ; SARS-CoV-2 ; Fatigue ; },
abstract = {BACKGROUND: Performance of activities of daily living (ADL) tasks is essential for most people's everyday lives. However, there is limited information regarding which ADL tasks and how their performances are typically impacted among persons with Long COVID.<br><br>AIM: To explore the types of ADL tasks typically affected and how the quality of ADL task performance is impacted in persons with long COVID and to explore relationships between ADL ability and health-related, social, or personal factors.<br><br>MATERIAL AND METHODS: This cross-sectional study involved individuals participating in a municipality-based rehabilitation program for persons with Long COVID. Data on ADL ability and health-related, social, and personal factors were gathered.<br><br>RESULTS: The sample included n&#x2009;=&#x2009;30 individuals with Long COVID. The participants reported decreased quality of ADL task performance related to both Personal ADL and Instrumental ADL tasks. A moderate relationship was identified between participants' ADL-I ability measures and ratings of fatigue. None of the remaining health-related, social and personal variables were related to ADL ability.<br><br>CONCLUSIONS: Individuals diagnosed with Long COVID reported decreased quality of performance in both PADL and IADL tasks, with increased time and effort being the primary issues. The most prevalent symptom, fatigue, was moderately related to participants' ADL ability.},
}
@article {pmid41347066,
year = {2025},
author = {Andreakos, E and Arkin, L and Bastard, P and Bolze, A and Borghesi, A and Brodin, P and Casanova, JL and Casari, G and Cobat, A and Drolet, B and Fellay, J and Hsieh, E and Meyts, I and Mogensen, TH and Sancho-Shimizu, V and Spaan, AN and Su, HC and Vinh, DC and Yatim, A and Zhang, Q and Zhang, SY and , },
title = {The seven enigmas of SARS-CoV-2: from the past to the future.},
journal = {Journal of human immunity},
volume = {1},
number = {4},
pages = {},
pmid = {41347066},
issn = {3065-8993},
support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 AI163029/AI/NIAID NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; },
abstract = {Five years ago, we launched the COVID Human Genetic Effort. Our goal was to explain the clinical variability among SARS-CoV-2-exposed individuals by searching for monogenic inborn errors of immunity (IEI) and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystemic inflammatory syndrome in children (MIS-C) in ~15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID-19 genetically and immunologically in one child, while we delineated the immunological mechanisms of COVID-toes in healthy children and young adults, paving the way for their genetic study. Understanding the human genetic and immunological basis of resistance to SARS-CoV-2 infection, long COVID, and myocarditis post mRNA vaccination, has been challenging and investigations remain ongoing. This work highlights the power of patient-based basic research and large-scale international collaborative efforts to discover human genetic and immunological drivers of infectious disease phenotypes, with implications for the timely development of new medical strategies before the next pandemic arrives.},
}
@article {pmid41346576,
year = {2025},
author = {Guimarães, GN and Brunetti, NS and De Lima, DG and Proenca-Modena, JL and Farias, AS},
title = {Vaccination and COVID-19: impact on long-COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1686572},
pmid = {41346576},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention &amp; control ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Vaccination ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long- and post-COVID-19 syndromes have emerged as a significant global health challenge, with millions of individuals experiencing persistent or the development of new symptoms after a long period of an initial SARS-CoV-2 infection. These symptoms are multisystemic and may indicate changes in the respiratory, neurological, cardiovascular and gastrointestinal systems, in addition to prolonged fatigue. Vaccination has played a crucial role in reducing severe disease and mortality, but the impact of the different vaccine combinations on the development and resolution of Long COVID remains a topic of debate. This review synthesizes current evidence on how different vaccine platforms, dosing strategies and booster doses influence the immunological response, protection, incidence, severity, and persistence of Long COVID symptoms. We discuss key immunological mechanisms by which vaccination may modulate and protect post-COVID syndrome outcomes, including its effects on viral clearance, immune response reprogramming, inflammation, and autoimmunity, seeking to combat misinformation and concepts spread by fake news. The review also highlights controversies and research gaps, such as variability in vaccine response among different populations and the role in the selection of more transmissible and virulent SARS-CoV-2 variants, as well as the potential differences between vaccine-induced and infection-induced immunity, and the role of pre-existing immune conditions in this scenario.},
}
@article {pmid41345969,
year = {2025},
author = {Wei, H and Daniels, S and Wiggans, R and Coleman, A and Bramwell, D and McElvenny, D and Forde, D and van Tongeren, M},
title = {Long COVID and work in the UK: challenges, support and perspectives.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {297},
pmid = {41345969},
issn = {0778-7367},
abstract = {AIM: Long COVID (LC) presents significant challenges for working age individuals, leading to major inequalities in access to work, employment and relevant support. This study investigates the workplace support provided to people with Long COVID (PwLC) in the UK, focusing on their return-to-work (RTW) experiences. It encompasses perspectives from both PwLC and managers of PwLC.<br><br>METHODS: Semi-structured interviews were conducted with 20 PwLC and two managers experienced in managing employees with LC. Inductive thematic analysis was performed using NVivo14.<br><br>FINDINGS: This qualitative research explored barriers and facilitators to supporting PwLC's RTW. LC is characterised by a wide range of mostly "invisible" and fluctuating symptoms and unpredictable recovery trajectories during which relapses can occur. Existing support mechanisms for RTW with LC include phased return, reduced hours, Occupational Health services, work adjustments, and government support. However, the study identified challenges in implementing these measures, such as unrealistic phased return plans, managers neglecting advice or guidance (e.g. from Occupational Health), unsuitable work adjustments and the burden of navigating government support. The financial impact of reduced hours or sick leave was one of the main reasons for returning to work. Both PwLC and managers highlighted significant gaps in knowledge, resources, policy and guidance for RTW support, emphasising the need for tailored support. Managers reported limited resources and inflexible policies as main challenges, which they addressed through creative solutions.<br><br>CONCLUSION: This qualitative study highlights potential barriers, challenges and gaps in supporting PwLC's RTW. To ensure equitable access to work for PwLC, a flexible and personalised approach is crucial, given the variability in LC symptoms and recovery rates. RTW support that fails to accommodate these characteristics may exacerbate symptoms or cause relapses. A supportive work environment is essential, as LC symptoms can be invisible and concerns about stigma may prevent PwLC from communicating openly and seeking support. Lack of resources is a major barrier for managers in supporting PwLC. Effective government support can potentially fill this gap but must be well-designed and implemented to reduce the burden on applicants.},
}
@article {pmid41344606,
year = {2025},
author = {Wee, LE and Tan, YY and Bin Abdul Malek, MI and Lim, JT and Chiew, CJ and Lye, DC and Tan, KB},
title = {Postacute sequelae following Omicron SARS-CoV-2 infection in transplant recipients: a population -based cohort study.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2025.11.025},
pmid = {41344606},
issn = {1600-6143},
abstract = {Population-based studies evaluating prevalence of postacute sequelae following coronavirus diseases 2019 (COVID-19), or long-COVID-19, in transplant recipients are limited. We examined the risk of long-COVID-19 following severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection with the Omicron variant, in a retrospective population-based cohort of transplant recipients vs test-negatives. National COVID-19/health care claims databases were used to construct cohorts of all Singaporean adult transplant recipients infected during Omicron predominance (January 1-December 31, 2022) and contemporaneous test-negatives. Competing-risks regression (death as a competing risk), with overlap weights applied, was used to estimate risks of new-incident diagnoses/symptoms 31 to 300 days post-SARS-CoV-2 infection in transplant recipients vs test-negatives. A total of 1890 SARS-CoV-2-infected transplant recipients and 1482 test-negatives were included. In total, 88.7% were boosted. Overall risks of postacute sequelae were not significantly increased in SARS-CoV-2-infected transplant recipients vs test-negatives (any postacute diagnosis: adjusted hazard ratio [aHR] = 1.35 [95% confidence interval {CI},
= 0.74-2.45]; any postacute symptom: aHR = 1.06 [95% CI = 0.52-2.17]). However, increased risk of postacute autoimmune (aHR = 5.34 [95% CI = 1.03-27.62])/neurologic sequelae (aHR = 3.06 [95% CI = 1.23-7.61]) was observed in SARS-CoV-2-infected transplant recipients vs test-negatives, though excess burden was modest (autoimmune: excess burden per 1000 individuals = 5.58 [95% CI = -4.49 to 15.65]; neurologic: excess burden per 1000 individuals = 19.82 [95% CI = -4.33 to 43.96]). Risks of postacute neurologic/autoimmune sequelae remained elevated in untreated COVID-19 cases vs test-negatives but did not significantly differ in treated COVID-19 cases vs test-negatives. We concluded that the overall risk of postacute sequelae was not significantly elevated in a highly vaccinated/boosted cohort of Omicron SARS-CoV-2-infected transplant recipients vs test-negatives. COVID-19 vaccination/boosting remains important during endemicity.},
}
@article {pmid41343834,
year = {2025},
author = {Rayner, C and Clarke, J},
title = {The C19-YRSm questionnaire for Long COVID.},
journal = {Occupational medicine (Oxford, England)},
volume = {75},
number = {8},
pages = {477-479},
doi = {10.1093/occmed/kqaf057},
pmid = {41343834},
issn = {1471-8405},
}
@article {pmid41341512,
year = {2025},
author = {Quimby, AE},
title = {Editorial: Exploring neurotological health concerns post-COVID-19 infection.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1731001},
pmid = {41341512},
issn = {1664-2295},
}
@article {pmid41341487,
year = {2025},
author = {Fujii, R and Kanata, S and Watanabe, Y and Kunugi, H},
title = {A case of Klinefelter syndrome presenting with an acute psychotic episode after COVID-19 infection.},
journal = {PCN reports : psychiatry and clinical neurosciences},
volume = {4},
number = {4},
pages = {e70262},
pmid = {41341487},
issn = {2769-2558},
abstract = {BACKGROUND: Klinefelter syndrome (KS) is a disease caused by a 47, XXY sex chromosome abnormality. It has been reported that KS not only causes physical problems but also confers the risk of developing psychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.<br><br>CASE PRESENTATION: Here we present a case of an 18-year-old male with complete KS who developed an acute psychotic episode after COVID-19 infection. The patient presented a catatonic state with stupor, rejection of others, and hallucinations that led him to self-injury. Psychotic symptoms improved in about 2 months with an antipsychotic, aripiprazole.<br><br>CONCLUSION: To our knowledge, this is the first report of a KS patient who acutely developed a psychotic disorder after COVID-19. Vulnerability to psychotic conditions of KS likely manifests as an acute psychotic episode facilitated by the neurotropic effects of COVID-19.},
}
@article {pmid41338651,
year = {2025},
author = {Mazurik, K and Amah, A and Dumitrescu, DI and Ejalonibu, H and Chavda, B and Kemp, D and Frederick, DE and Mclean, C and Décary, S and Gruneir, A and Halas, G and Hoens, A and Kho, M and , and Groot, G},
title = {Developing a minimum dataset for a national patient registry on Long COVID in Canada: a Delphi consensus-based study.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e111474},
pmid = {41338651},
issn = {2044-6055},
mesh = {Humans ; Canada/epidemiology ; Delphi Technique ; *Registries ; *COVID-19/epidemiology/complications ; Consensus ; Quality of Life ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; *Datasets as Topic ; },
abstract = {OBJECTIVES: To develop survey items for a national patient registry on Long COVID using a modified Delphi process.<br><br>DESIGN: This study was based on a modified Delphi process involving three rounds of anonymous, online surveys to develop consensus on and prioritise survey elements to be included in a minimum dataset for use in a national patient registry in Canada. Initial Long COVID items were identified through an environmental scan of the literature.<br><br>SETTING: This study focused on healthcare systems in Canada and was conducted online.<br><br>PARTICIPANTS: A panel of 52 experts (patients, caregivers, clinicians and researchers) participated in all three rounds of the online survey. These participants were recruited through the Long COVID Web network and word of mouth.<br><br>RESULTS: In total, 243 survey elements related to care, quality of life and symptoms were included in round 1 of the survey. 200 reached consensus and moved to round 2 with two additional elements being developed based on open-ended responses. In round 2, participants ranked these survey elements and 34 advanced. In round 3, 33 survey elements met the threshold of consensus with one added a priori. The 33 survey elements were then used to develop a Long COVID minimum dataset, which consists of 48 items.<br><br>CONCLUSIONS: The findings affirm broad consensus for collecting data related to fatigue, post-exertional malaise, cardiovascular issues, respiratory problems and cognitive issues. This highlighted the desire for quality-of-life indicators and information related to care utilisation, quality and access.},
}
@article {pmid41337380,
year = {2025},
author = {Kerezis, A and Antonoglou, A and Asimakos, A and Athanasiou, N and Spetsioti, S and Dalakleidi, K and Asvestas, P and Katsaounou, P and Golemati, S},
title = {A Machine Learning Framework for Efficient Triage of Long-COVID Patients to Specialists.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-4},
doi = {10.1109/EMBC58623.2025.11252756},
pmid = {41337380},
issn = {2694-0604},
mesh = {Humans ; *Triage/methods ; *COVID-19/diagnosis/therapy ; *Machine Learning ; SARS-CoV-2 ; Support Vector Machine ; Male ; Female ; Middle Aged ; },
abstract = {Long-COVID poses a significant burden on healthcare systems, necessitating efficient triaging strategies to optimise patient care. This study presents a machine learning (ML) framework for prioritising long-COVID patients for specialist consultations in cardiology, pulmonology, and psychiatry. Utilising a dataset of 175 patients, a Support Vector Machine model was developed, and subsequently enhanced with Synthetic Minority Oversampling Technique for class imbalance handling. The model yielded an accuracy of 0.67 and an Area-Under-the-Curve of 0.84, outperforming alternative models such as Random Forest, k-nearest neighbours, XGBoost, and Decision Trees. Notably, the SF-36 General Health score emerged as the most critical factor in patient classification, followed by bodily pain and anxiety levels. These findings demonstrate the potential of ML-based approaches to streamline healthcare resource allocation and improve patient outcomes. Future work will assess the clinical impact of this approach in prospective studies.Clinical Relevance- This study proposes a machine-learning-driven method to enhance specialist triaging for long-COVID patients, offering potential for improved healthcare resource allocation and timely patient care.},
}
@article {pmid41332817,
year = {2025},
author = {Peng, B and Dalhuisen, T and Rogers, A and Capric, V and Davies, HE and Deeks, SG and Dupont, CL and Estevez, J and Freire, M and Haddad, NS and Jones, SA and Kelly, JD and Ladell, K and Lee, FE and Martin, JN and Miners, KL and Peluso, MJ and Price, DA and Proal, AD and Putrino, D and Scheuermann, RH and VanElzakker, MB and Zhang, Y and Tan, GS and Qian, Y},
title = {Machine Learning Analysis of Post-Acute COVID Symptoms Identifies Distinct Clusters, Severity Groups, and Trajectories.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.16.25340350},
pmid = {41332817},
abstract = {Questionnaires that capture patient-reported symptomatology provide low-cost but potentially high-value data for the de novo discovery of disease phenotype, severity, and responsiveness to intervention groupings within an umbrella condition. The availability of comprehensive electronic health records (EHRs) has nonetheless overshadowed the use of questionnaires data for symptom analysis in the context of COVID-19. We analyzed de-identified questionnaires from post-acute COVID-19 cohorts at the University of California, San Francisco (UCSF, n = 669), Icahn School of Medicine at Mount Sinai (ISMMS, n = 615), Emory University (Emory, n = 60), and the University Hospital of Wales (Cardiff, n = 317). Using topic modeling followed by unsupervised clustering, we identified distinct symptom clusters and their corresponding symptom signatures. Mapping these signatures to organ systems revealed nine to twelve endotypes per cohort, capturing the heterogeneity of post-COVID-19 symptoms. Some clusters were associated with pre-existing conditions, including a female-predominant severity cluster with neurological and hormonal symptoms. Longitudinal analysis distinguished three symptom trajectories of individual symptoms: acute then resolving, persistent but attenuated, and progressive disease. Symptom severity correlates between the acute and the long COVID phases. Individuals with non-mild symptoms in the acute phase have 2.6 times the risk of developing moderate or severe long COVID symptoms, compared with individuals with mild symptoms in the acute phase. Across all cohorts, three severity levels, namely, mild, moderate, and severe, were evident from symptoms alone. Symptom-based severity scores correlated with patient-reported health status (EQ-5D) and SARS-CoV-2-specific antibody responses in plasmablasts, validating the prediction. Cluster-level analyses further stratified patients into recovered and non-recovered subgroups, identifying endotypes associated with different recovery trajectories. Finally, meta-analysis integrating cohort-specific clusters defined ten global endotypes and a unified map of severity scores, highlighting cohort-specific patterns, sex differences, and relationships among organ systems. These findings demonstrate that machine learning-assisted screening of questionnaire data can robustly identify symptom clusters, endotypes, and severity groups, providing a framework for stratifying long COVID patients for precision medicine trial design.},
}
@article {pmid41332799,
year = {2024},
author = {Lee, H and Choi, S and Eom, E and Song, GH and Kim, SS},
title = {[Introduction to the Research Results of Coronavirus Disease 2019 Big Data (K-COV-N) and the Corresponding Utilization Plan].},
journal = {Jugan geon-gang gwa jilbyeong},
volume = {17},
number = {48},
pages = {2147-2159},
pmid = {41332799},
issn = {2586-0860},
abstract = {As part of the effort to establish a scientific basis for quarantine policies aimed at responding to new infectious diseases based on the experience of responding to coronavirus disease 2019 (COVID-19), the Korea Disease Control and Prevention Agency (KDCA) and National Health Insurance Service promoted the establishment of health information big data and signed a business agreement (April 29, 2021). The big data created by combining the KDCA’s COVID-19 confirmed cases and vaccination data with the National Health Insurance Service’s national health information are known as K-COV-N (KDCA Covid-19 NHIS cohort). The big data constructed were opened to the private sector through the National Health Insurance Service’s open platform to promote private research. A cumulative total of 211 cases have been approved since the opening of COVID-19 big data from April 2022 until October 2, 2024, and a total of 30 papers have been published in international journals. The main contents were research results such as COVID-19 infection risk factors, vaccination effects, and long COVID. In addition, after the opening of big data, we held workshops on practical networking for utilizing COVID-19 big data to share analyses and techniques for utilizing the data. Additionally, we established a public-private data analysis network to promote exchanges between practitioners. In addition, we are contributing to the activation of private research by expanding ties with the National Cancer Center and health-information-holding organizations. Accordingly, the KDCA plans to continue opening up infectious disease-related information to develop evidence-based quarantine policies and support expert decision-making.},
}
@article {pmid41332658,
year = {2025},
author = {Pesqueira Sanchez, MA and de Necochea Campion, R and Dalhuisen, T and Fehrman, EA and Chhabra, PS and Kelly, JD and Martin, JN and Deeks, SG and Henrich, TJ and Peluso, MJ and LaRosa, SP},
title = {Increased mannosylation of extracellular vesicles in Long COVID plasma provides a potential therapeutic target for Galanthus nivalis agglutinin (GNA) affinity resin.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332658},
issn = {2692-8205},
support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; },
abstract = {There is no proven therapy for Long COVID, a post-acute illness characterized by a myriad of diverse symptoms including fatigue, dyspnea, and brain fog following SARS-CoV-2 infection. Extracellular vesicles (EVs) have been implicated in Long COVID pathogenesis by promoting viral and inflammatory signaling with their molecular cargo. In this study, we investigated whether EV abundance and glycome characteristics are altered in plasma from people with Long COVID and whether they can be targeted for removal using a glycan-binding affinity resin. Large (100-500 nm) and small (40-200 nm) EVs were isolated from plasma of participants in the post-acute phase of COVID-19 and analyzed by nanoparticle flow cytometry to measure concentration and glycan characteristics. Plasma of those with Long COVID contained elevated levels of both large and small EVs, and mannose-positive large EVs were significantly increased in comparison to recovered controls (p < 0.05). EV capture assays using Galanthus nivalis agglutinin (GNA) affinity resin demonstrated small EV removal positively correlated with mannose-positive EV abundance (r = 0.341, p < 0.05). NanoString analyses identified seven EV-associated miRNAs significantly depleted by GNA affinity resin treatment of plasma. PROGENy pathway inference of validated miRNA-mRNA interactions suggests these reductions may lead to a downregulation of JAK-STAT signaling and upregulation of Estrogen, VEGF, and PI3K pathways, resulting in a favorable rebalancing of immune and tissue-repair networks. These findings reveal specific glycome EV-miRNA cargo signatures in Long COVID and the potential clinical benefits of a lectin capture therapeutic strategy to remove these pathogenic vesicles and their inflammatory cargo.},
}
@article {pmid41332203,
year = {2025},
author = {Leighton, J and Heldmann, I and Van de Ven, K and Reis, L and Vijayakumar, A and Simpson, R and Nelson, M and Sheppard, C and Robinson, LL and Steinberg, R and Nguyen, M and Bayley, M and Daneman, N and Levy, C and Ho, C and Goulding, S and Hitzig, SL and Wasilewski, MB},
title = {Rehabilitation providers' experiences with long COVID care in Canada: a qualitative study.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09638288.2025.2583734},
pmid = {41332203},
issn = {1464-5165},
abstract = {PURPOSE: To examine the experiences, challenges, and recommendations of Canadian Rehabilitation Providers delivering care to people with Long COVID (PWLC), with the goal of informing best practices and guiding service and policy improvements.<br><br>MATERIALS AND METHODS: A qualitative descriptive study was conducted using semi-structured interviews with 32 Rehabilitation Providers from multiple disciplines and provinces across Canada. Participants were purposively sampled and interviewed between April 2022 and January 2023. Data were analyzed using codebook thematic analysis, incorporating inter-coder and inter-rater agreement and reflexivity practices.<br><br>RESULTS: Three central themes emerged: (1) Providers faced substantial barriers, including limited infrastructure, resource constraints, and misinformation about Long COVID; (2) In the absence of formal guidelines, providers adapted their practices through individualized care planning, trial-and-error, and peer learning; and (3) Participants emphasized key components of effective rehabilitation, such as validating patient experiences, promoting self-management and pacing, integrating caregiver support, facilitating peer connections, and fostering inter-professional collaboration.<br><br>CONCLUSION: Rehabilitation Providers have been critical in addressing the evolving needs of PWLC despite inadequate systemic support. Their insights point to the need for coordinated, interdisciplinary, and patient-centered care models, alongside investment in professional training, system infrastructure, and integrated policy responses for current and future post-viral conditions.},
}
@article {pmid41331993,
year = {2025},
author = {Palm, ME and Gu, CA and Bassett, IV and Levy, BD and Chen, LQ and John, J and Johnson, C and Lindsay, J and Lobb, R and McCray, N and Ojikutu, B and Martinez, LS and Rodriguez-Louis, J and Rushforth, A and Torres, R and Zionts, DL and Clark, CR},
title = {Community Engagement in Long Covid: Insights From the Boston COVID Recovery Cohort.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70493},
pmid = {41331993},
issn = {1369-7625},
support = {//This study was supported in part by a grant from the National Institutes of Health to fund the Researching COVID to Enhance Recovery (RECOVER) initiative, reference number 1OT2HL161847-01./ ; },
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology/therapy ; Boston/epidemiology ; *Community Participation/methods ; SARS-CoV-2 ; Cohort Studies ; Academic Medical Centers ; },
abstract = {BACKGROUND: In 2021, the National Institutes of Health launched a multi-centre observational study on long Covid: Researching COVID to Enhance Recovery (RECOVER). Six Boston academic medical centres joined community partners to become the Boston COVID Recovery Cohort (BCRC), a consortium of RECOVER sites. Our consortium developed a community engagement model, and this manuscript shares lessons and recommendations.<br><br>DESIGN AND PARTICIPANTS: The BCRC Community Partnership Table, which included community partners, senior equity leaders, academic researchers and health system collaborators, co-developed a charter to advance research, community education, clinical care, social support and institutional and policy change goals. BCRC engaged patients, providers, caregivers and legislators via multiple communication channels.<br><br>FINDINGS: The BCRC Community Partnership Table faced several challenges: working within a novel, evolving pandemic; structural barriers to successful community engagement; perspectives on trustworthiness of research; and working across multiple organisations with distinct structures, resources and goals. There were also successes: leaders who were invested in community engagement; a focus on inclusive network building; co-production; flexible communication channels; a shift to centring communities and patients; and connection with the legislature to support broader policy impacts.<br><br>DISCUSSION: To inform future community engagement models, we recommend the following: (1) healthcare research funders should build in time and resources for community engagement; (2) study consortia should include community engagement specialists in decision-making positions from the outset; and (3) community members should have prominent roles leading research engagement efforts.<br><br>CONCLUSIONS: Engagement models can enhance the equity impact of long Covid research. Reflections and recommendations in this paper can inform future efforts.<br><br>The project included community leaders, community-based organisations, people with long Covid, and those caring for people with long Covid. Community leaders, community-based organisations and people with long Covid are included in every aspect of the network. They inform decision-making, play a key role in network leadership and are also all represented within the authorship team.},
}
@article {pmid41331825,
year = {2025},
author = {Vicente-Gómez, J&#xc1; and de Muniategui Climente, M and Loste, C and Barreales, S and Ríos, LR and Paredes, R and Mateu, L and Segui, FL},
title = {Post-COVID-19 condition patients' utilisation of healthcare resources after implementation of an integrated care unit.},
journal = {Cost effectiveness and resource allocation : C/E},
volume = {23},
number = {1},
pages = {72},
pmid = {41331825},
issn = {1478-7547},
abstract = {BACKGROUND: The economic effects of post-COVID-19 condition (PCC) remain uncertain despite clearer clinical factors, posing challenges for healthcare professionals. This article investigates the demographic and clinical characteristics of PCC patients and compares their healthcare resource utilization in comparison to a patient cohort representative of the population.<br><br>METHODS: A retrospective and cohort-comparative observational study was conducted, comparing PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed to describe the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary and emergency care.<br><br>RESULTS: PCC patients (N&#x2009;=&#x2009;341) were older with higher cardiovascular risk factors compared to controls (N&#x2009;=&#x2009;49,078). There were differences in the socio-economic distribution between male and female in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. PCC patients were four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations.<br><br>CONCLUSIONS: Coordinated care for PCC patients leads to cost reductions and improved resource utilisation. Further research should investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12962-025-00667-z.},
}
@article {pmid41326934,
year = {2025},
author = {O'Hare, AM and Montague, K and Hynes, DM and Fox, A and Nye, V and Iwashyna, TJ and Card, H and Tuepker, A and Helfand, M and Vig, EK and Butler, CR and Taylor, JS and Viglianti, EM and Jones, BE and Knight, SJ and Eaton, TL and Bowling, CB and Maciejewski, ML and Bohnert, AS and Ioannou, GN and Nugent, SM and , },
title = {Illness Experiences of Veterans Reporting Long-Term Symptoms or Health Challenges from COVID-19: Results from the VA COVID-19 Observational Research Collaboratory.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41326934},
issn = {1525-1497},
support = {C19 21-279//U.S. Department of Veterans Affairs/ ; },
abstract = {BACKGROUND: Our understanding of the illness experience of long COVID comes mostly from studies conducted among long COVID online communities and support groups or participants in cohort studies of COVID-19.<br><br>OBJECTIVE: To elicit the illness experiences of patients receiving care in real-world clinical settings experiencing ongoing symptoms or health challenges from COVID-19.<br><br>DESIGN AND PARTICIPANTS: Qualitative interview study conducted between July 2022 and April 2024 among 39 patients identified in health system data who indicated that they were experiencing ongoing symptoms or health challenges from COVID-19.<br><br>APPROACH: Qualitative analysis of participants' post-COVID-19 illness experience from one-time semi-structured in-depth interviews.<br><br>KEY RESULTS: Participants' mean age was 63.6&#xa0;years (SD 13.2&#xa0;years), 8 (20.5%) were identified in VA data as female, 6 (15.4%) as Black, 29 (74.4%) as White, and 2 (5.1%) as Hispanic. Interviews were conducted an average of 23&#xa0;months after the initial COVID infection (range 8 to 49&#xa0;months) and lasted an average of 87 (SD 27.3) minutes.&#xa0;Participants varied in their embrace of long COVID as an organizing framework for their post-COVID illness experience, reflecting two dominant themes: (1) Interpreting complexity: Study participants often had difficulty disentangling the long-term effects of COVID-19 from those of their other health conditions and normal aging. Their baseline health status, post-COVID illness trajectory, and expectations of aging shaped how they made sense of their illness experience; (2) Seeking answers: Though often fraught with uncertainty, participants' interpretation of their post-COVID illness experience was shaped more by clinical encounters and diagnostic evaluation than by interactions with others with relatable illness experiences.<br><br>CONCLUSIONS: Our findings illuminate the challenges of applying a broadly defined diagnostic category lacking condition-specific markers in real-world clinical settings and the role of health systems and providers in the ongoing social construction of long COVID.},
}
@article {pmid41325417,
year = {2025},
author = {Pinero, S and Li, X and Liu, L and Li, J and Lee, SH and Winter, M and Nguyen, T and Zhang, J and Le, TD},
title = {Integrative multi-omics framework for causal gene discovery in Long COVID.},
journal = {PLoS computational biology},
volume = {21},
number = {12},
pages = {e1013725},
pmid = {41325417},
issn = {1553-7358},
mesh = {Humans ; *COVID-19/genetics ; Genome-Wide Association Study ; Quantitative Trait Loci/genetics ; SARS-CoV-2 ; Protein Interaction Maps/genetics ; Computational Biology/methods ; Transcriptome/genetics ; Mendelian Randomization Analysis ; Genetic Predisposition to Disease ; Post-Acute COVID-19 Syndrome ; Gene Expression Profiling ; Gene Regulatory Networks ; Multiomics ; },
abstract = {Long COVID, or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), affects an estimated 10-20% of COVID-19 patients and presents persistent multisystemic symptoms. Although demographic and clinical factors, such as age, sex, and comorbidities, contribute to risk, the genetic mechanisms underlying this risk remain poorly defined. To address this gap, we developed a multi-omics framework that integrates Transcriptome-Wide Mendelian Randomization (TWMR), Control Theory (CT), Expression Quantitative Trait Loci (eQTL), Genome-Wide Association Studies (GWAS), RNA sequencing (RNA-seq), and Protein-Protein Interaction (PPI) network to identify putative causal genes and network drivers in Long COVID. Our approach prioritized 32 candidate genes, including 19 previously reported and 13 novel, with roles in the SARS-CoV-2 response, viral carcinogenesis, immune regulation, and cell cycle control. Enrichment analyses revealed a shared genetic architecture in syndromic, metabolic, autoimmune, and connective tissue disorders. Using causal gene expression profiles, we identified three distinct symptom-based subtypes of Long COVID, providing information on the heterogeneity of disease mechanisms and clinical presentation. Finally, we developed an open-source Shiny application for interactive exploration of these findings. Together, this integrative framework highlights novel causal mechanisms and therapeutic targets, advancing precision medicine strategies for Long COVID.},
}
@article {pmid41324571,
year = {2025},
author = {Metaxaki, M and Ram, R and Perera, M and Wills, M and Krishna, BA and Sithole, N},
title = {Robust antibody and T cell responses tracked longitudinally in patients with long COVID.},
journal = {The Journal of general virology},
volume = {106},
number = {12},
pages = {},
pmid = {41324571},
issn = {1465-2099},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *COVID-19/immunology/virology ; *Antibodies, Viral/blood/immunology ; Male ; Female ; *SARS-CoV-2/immunology ; Middle Aged ; Interferon-gamma/blood/immunology ; Retrospective Studies ; Antibodies, Neutralizing/blood/immunology ; Interleukin-2/immunology/blood ; Aged ; *T-Lymphocytes/immunology ; Adult ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; },
abstract = {After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a minority of patients experience persistent or emerging symptoms, termed 'long coronavirus disease (COVID)' or post-acute sequelae of COVID-19. The molecular causes of long COVID remain unclear, but disrupted immune functions, such as inflammation and immune deficit, have been posited as factors. In this retrospective cohort study, we measured markers of immune function in a group of patients with long COVID up to 40 months post infection. As proxies for immune function, we measured serum antibody levels, antibody neutralizing capability and production of IFN gamma (IFN-γ) and IL-2 against SARS-CoV-2 and other viral peptides. As expected, serum antibody levels increased over time with vaccinations and reinfections with later variants of SARS-CoV-2. Patients also showed corresponding increasing SARS-CoV-2-specific IL-2 responses and stable IFN-γ responses. We observed no significant differences in immune responses among patients with ongoing long COVID, those who had recovered from it or individuals who recovered from acute COVID-19. Overall, we found no indication of a reduction in these aspects of immune function after SARS-CoV-2 infection. This study provides a valuable foundation for further research aimed at understanding the causes of long COVID.},
}
@article {pmid41323230,
year = {2025},
author = {Furevik, LL and Lapina, O and Lindland, ES and Høgestøl, EA and Geier, OM and Devik, K and Farmen, AH and Flemmen, H&#xd8; and Harbo, HF and Morsund, &#xc5;H and Novotny, V and Ofte, HK and Pedersen, KO and Popperud, TH and Ratajczak-Tretel, B and Samsonsen, C and Selnes, P and Torkildsen, &#xd8; and Undseth, RM and Aamodt, AH and Beyer, MK and Boldingh, MI},
title = {Brain MRI findings in patients with post COVID-19 condition: frequency and longitudinal changes in a nationwide cohort study.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1662263},
pmid = {41323230},
issn = {1664-2295},
abstract = {BACKGROUND: Prolonged neurological symptoms following COVID-19 are common, yet few longitudinal studies describe brain MRI findings in this patient group. The use of contrast enhanced sequences is particularly lacking. We address this knowledge gap by reporting the frequency and longitudinal changes in brain MRI findings among patients with post COVID-19 condition exhibiting neurological symptoms.<br><br>METHODS: This prospective multicenter study included 140 adult patients referred for persistent neurological symptoms following COVID-19. Brain MRI was performed at both 6 and 12&#x202f;months after infection onset, reporting white matter hyperintensities, cerebral microbleeds, and additional pathological findings including contrast enhancement. White matter hyperintensities were compared with a healthy control group.<br><br>RESULTS: The prevalence of white matter hyperintensities was comparable to healthy controls, and microbleeds were found at rates comparable to population studies, with longitudinal changes being infrequent. Lesions consistent with inflammation or demyelination were present in 4% (5/120) of patients at 6 months. Cranial nerve enhancement was found in 7% (7/94) of patients, persisting up to 12&#x202f;months, predominantly affecting the oculomotor nerve. However, enhancement occurred without clinically detected ocular muscle paresis.<br><br>CONCLUSION: Our findings indicate that brain MRI primarily serves to exclude differential diagnoses in post COVID-19 condition, with limited clinical benefit of repeated imaging in the absence of new symptoms. However, signs of long-term inflammatory processes can be observed, and detection is improved by contrast enhanced sequences.},
}
@article {pmid41322411,
year = {2025},
author = {Liu, H and Xu, Z and Karsidag, I and Wang, P and Weng, J},
title = {Correction: Immune cell communication networks and memory CD8+ T cell signatures sustaining chronic inflammation in COVID-19 and Long COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1739646},
doi = {10.3389/fimmu.2025.1739646},
pmid = {41322411},
issn = {1664-3224},
abstract = {[This corrects the article DOI: 10.3389/fimmu.2025.1689507.].},
}
@article {pmid41319836,
year = {2026},
author = {Li, Y and Tao, Y and Zhao, Z and Zhong, P and Zhong, L and Yang, H and Yu, M and Liu, S and Lei, K and Zhao, Q and Wang, R and Wang, J and Zeng, Q and Kuang, S and Li, T},
title = {Long COVID as an independent predictor of myasthenia gravis exacerbation: A prospective cohort study integrating machine learning for risk stratification.},
journal = {Respiratory medicine},
volume = {251},
number = {},
pages = {108554},
doi = {10.1016/j.rmed.2025.108554},
pmid = {41319836},
issn = {1532-3064},
mesh = {Humans ; *Myasthenia Gravis/epidemiology/complications ; *COVID-19/complications/epidemiology ; *Machine Learning ; Male ; Female ; Middle Aged ; Prospective Studies ; Risk Assessment/methods ; Aged ; Disease Progression ; SARS-CoV-2 ; Adult ; Severity of Illness Index ; China/epidemiology ; },
abstract = {OBJECTIVES: This study evaluates the impact of long coronavirus disease (Long COVID) on disease exacerbation in patients with myasthenia gravis (MG) and leverages machine learning (ML) approaches to identify high-risk patients.<br><br>METHODS: Patients with MG and COVID-19 co-infection were recruited from December 5, 2022, to January 20, 2023, at the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine (ChiCTR2400087937). Participants underwent structured interviews at 1, 6, and 12 months post-COVID-19 to assess the incident Long COVID and MG exacerbation. The primary outcomes included the incidence and severity of MG exacerbation; the secondary outcome was 12-month mortality. Cox proportional hazards regression was employed to explore the correlation between Long COVID and MG exacerbation. ML algorithms were implemented for predictive modeling.<br><br>RESULTS: Among 180 patients, 62 (34.4&#xa0;%) experienced MG exacerbation within 12 months, and severe exacerbations (MG-ADL &#x2265;6 points) accounted for 43.5&#xa0;% of cases. Among those with initial MG exacerbations, 14.4&#xa0;% continued to exhibit persistent symptoms without full recovery by the 12-month follow-up. Six fatalities (3.3&#xa0;%) were recorded. Long COVID served as the strongest predictor of exacerbation (aHR&#xa0;=&#xa0;2.55, 95&#xa0;% CI 1.47-4.42, P&#xa0;=&#xa0;0.001), followed by acetylcholinesterase (AChE) inhibitor use (aHR&#xa0;=&#xa0;2.38) and severe COVID-19 classification (aHR&#xa0;=&#xa0;2.30). The Random Forest model (RF) outperformed other algorithms, achieving an AUC of 0.83, with Long COVID as the top predictive feature.<br><br>CONCLUSIONS: Long COVID is associated with MG exacerbation over time. RF model shows potential as a scalable tool for MG exacerbation risk stratification.},
}
@article {pmid41318861,
year = {2026},
author = {Yadav, JP and Yadav, S and Dubey, NK and Yadav, IP and Pathak, P and Verma, A},
title = {Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.},
journal = {Inflammopharmacology},
volume = {34},
number = {1},
pages = {17-46},
pmid = {41318861},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/therapy/complications/physiopathology/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use ; },
abstract = {Throughout the world-wide COVID-19 pandemic, there has arisen a significant and a sustained public-health issue, whereby a significant proportion of individuals report persistent symptoms, well beyond the acute period of infection. The non-united array of chronic, multisystemic events, such as fatigue, cognitive deficit, respiratory dysfunction, cardiovascular abnormalities, and neuropsychiatric disorders characterize this sequela, which is referred to as LCS. LCS is much more than the starting viral insult, as it causes long-term complications that impact various organ systems. The current review questions the pathophysiological mechanisms of LCS, including scrutinizing the importance of the dysregulation of immunity, the persistence of viral reservoirs, endothelial dysfunction, autonomic imbalance, and mitochondrial injury. We highlight the heterogeneity of the syndrome and the associated diagnostic and treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies, including pharmacologic therapy (immunomodulators, anticoagulants, antiviral medications, etc.) and non-pharmacologic treatment (rehabilitative programs, etc.) are discussed against the backdrop of recent clinical findings. This review incorporates the recent literature and presents a review of potential treatment options that alleviate symptoms and improve the quality of life of LCS patients. Finally, this integrated synthesis can be used by both clinicians and researchers to gain practical information on the diagnosis, treatment, and future treatment directions of LCS.},
}
@article {pmid41316208,
year = {2025},
author = {Ouazana Vedrines, C and Gouraud, C and Scherlinger, M and Betouche, S and Carrat, F and Caumes, E and Pitron, V and Robineau, O and Sibilia, J and Thoreux, P and Xiang, K and Ranque, B and Lemogne, C and , },
title = {Excess of infection with SARS-CoV-2 during the first versus second wave of the COVID-19 pandemic among patients with long COVID.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {4355},
pmid = {41316208},
issn = {1471-2458},
abstract = {BACKGROUND: Post-COVID-19 condition affects up to 10% of patients months after a COVID-19 episode. Population-based epidemiology suggests that self-reported long COVID in France might be more common among those infected during the first wave of the pandemic than the second one, supporting the role of contextual risk factors in symptom persistence in some patients. We aimed to examine whether this pattern could also be observed in a clinical setting, considering patients with well-characterized post-COVID-19 condition and the general population.<br><br>METHODS: In a case-population study, we compared the rate of SARS-CoV-2 infection during the first wave (January 1 to May 11, 2020) versus the second wave, which involved the same historical variant (May 12, 2020 to January 15, 2021) between patients with post-COVID-19 condition assessed during a multidisciplinary day-hospital program and the general population. Binary logistic regression was used to compute odds ratio (OR) and 95% confidence interval (CI) for infection during the first versus the second wave.<br><br>RESULTS: Among 177 consecutive patients, the odds of reporting SARS-CoV-2 infection during the first versus the second wave were significantly higher than in the Paris area general population (OR [95% CI]: 1.74 [1.27&#x2013;2.40]), p&#x2009;<&#x2009;0.001). The results remained similar in sensitivity analyses considering the French general population (1.36 [1.02&#x2013;1.88]).<br><br>CONCLUSIONS: These results further suggest the role of contextual factors in long COVID and the relevance of a biopsychosocial perspective.},
}
@article {pmid41316170,
year = {2025},
author = {Joy, M and Adams, N and Yanuck, M and Dossett, ML},
title = {Experiences with Qi and changes in post-acute sequelae of COVID-19 (PASC) symptoms with qigong: a qualitative analysis of participants' experiences in a pilot clinical trial.},
journal = {BMC complementary medicine and therapies},
volume = {25},
number = {1},
pages = {434},
pmid = {41316170},
issn = {2662-7671},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/complications/therapy ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; *Qigong/methods ; Qualitative Research ; Quality of Life ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Commonly known as "long COVID", post-acute sequelae of COVID-19 (PASC) is a chronic condition with no validated treatment that significantly impacts the quality of life of those affected. Qigong is a Traditional Chinese Medicine (TCM) practice that may serve as a possible therapeutic approach for PASC. This study explored participants' experiences with qi, and changes in PASC symptoms, following participation in a clinical trial of group-based, combined external and internal qigong for individuals with PASC.<br><br>METHODS: A qualitative study of 26 individuals who participated in a pilot feasibility trial of qigong for PASC symptoms was performed. Participants engaged in six weekly, two-hour sessions of external and internal qigong delivered in a group-based format. Upon completion of the intervention, all participants were interviewed using a semi-structured interview guide. The interviews were transcribed, coded and analyzed using a conventional content analysis approach to explore participants' perceptions and understanding of qi, qigong, and the overall impact of the sessions on their well-being and PASC symptoms.<br><br>RESULTS: Participants' understanding and explanations of qi varied. Almost all participants (92%) reported feeling qi during the sessions, and a variety of different sensations associated with perception of qi were described. Approximately three-quarters of participants experienced improvement in one or more PASC symptoms, most commonly fatigue, "brain fog", and sleep quality, and 85% reported improved well-being. Additionally, participants frequently cited the group-based nature of the intervention as a positive aspect of their experience.<br><br>CONCLUSIONS: The qigong intervention was well-received by participants, with the majority perceiving qi and reporting improvements in PASC-related symptoms and overall well-being. These findings suggest that many individuals may be able to perceive qi and that group-delivered combined external and internal qigong may be a beneficial complementary therapy for managing PASC symptoms. As this is a pilot study with a small sample size and a single qigong teacher, results must be interpreted cautiously. Further research is warranted to evaluate the effects of qigong in this patient population.<br><br>TRIAL REGISTRATION: Registry: ClinicalTrials.gov.&#xa0;Trial Registration Number: NCT05675995.&#xa0;Date of Registration: January 4, 2023.},
}
@article {pmid41316069,
year = {2025},
author = {Spielmann, J and Pink, I and Framme, C and Tode, J and Volkmann, I},
title = {Association of foveal avascular zone (FAZ) enlargement with SARS-CoV-2 infection and long COVID-19.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {680},
pmid = {41316069},
issn = {1471-2415},
mesh = {Humans ; *COVID-19/complications ; Male ; *Fovea Centralis/blood supply/diagnostic imaging/pathology ; Female ; Prospective Studies ; Middle Aged ; Tomography, Optical Coherence/methods ; Case-Control Studies ; *Retinal Vessels/pathology/diagnostic imaging ; *SARS-CoV-2 ; Fluorescein Angiography/methods ; Adult ; Aged ; *Retinal Diseases ; Fatigue ; },
abstract = {BACKGROUND: As COVID-19 was found to affect small vessels of multiple organ systems, the purpose of the study is to describe the macular vessel density (VD) and the area of the foveal avascular zone (FAZ) by optical coherence tomography angiography (OCTA) in patients who recovered from a COVID-19 disease, who were or were not treated in an Intensive Care Unit (ICU) and who suffer from fatigue due to long COVID.<br><br>METHODS: Prospective case-control study in which laboratory-confirmed and recovered COVID-19 patients were included. Macular OCTA was performed at least seven weeks after initial COVID-19. The VD of the superficial retinal capillary plexus (SCP) and the area of the FAZ were measured. Results were compared among ICU- and non-ICU COVID-19 patients and a healthy control group; moreover, patients were divided into groups of no fatigue, fatigue, and extreme fatigue and results were compared among these and a control group.<br><br>RESULTS: FAZ of non-ICU patients was significantly enlarged compared to control group. VD was not significantly different among these cohorts. FAZ of fatigue group was significantly enlarged compared to no fatigue group and control group. VD of extreme fatigue group was significantly greater than VD of both no fatigue group and control group.<br><br>CONCLUSION: The retinal microvasculature of recovered COVID-19 patients showed alterations in the sense of a significantly enlarged FAZ, particularly in patients with mild disease and fatigue. These microvascular manifestations may lead to future complications or visual impairment. Performing macular OCTA could be a possible monitoring tool for microvascular changes in these patients and a predictor for long COVID fatigue.},
}
@article {pmid41314260,
year = {2026},
author = {Felix, DM and Mohandas, VJ and de Andrade Leão, OA and Siqueira, FV and Hallal, PC},
title = {Physical activity and post-COVID symptoms: Findings from the EPICOVID 2.0 survey in Brazil.},
journal = {Preventive medicine},
volume = {203},
number = {},
pages = {108471},
doi = {10.1016/j.ypmed.2025.108471},
pmid = {41314260},
issn = {1096-0260},
mesh = {Humans ; Brazil/epidemiology ; *Exercise/physiology ; *COVID-19/epidemiology/complications ; Male ; Female ; Adult ; Middle Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Socioeconomic Factors ; Aged ; Self Report ; Pandemics ; Adolescent ; Sociodemographic Factors ; Fatigue/epidemiology ; Young Adult ; },
abstract = {OBJECTIVE: This study primarily aims to analyze changes in physical activity after the COVID-19 pandemic in Brazil and their association with post-COVID symptoms. We also examined associations between sociodemographic variables (sex, region, wealth quintile, education, age, and race/ethnicity) and physical activity.<br><br>METHODS: Using data from the 2024 Brazilian national survey EPICOVID 2.0, with 33,250 participants, we analyzed self-reported changes in physical activity during the pandemic. To test associations between four categories ("Never Practiced" as reference category, "Decreased", "Maintained", or "Increased") and 14 post-COVID symptoms, we used adjusted Logistic regression models. Establishing a threshold of p&#xa0;<&#xa0;0.004, after Bonferroni correction.<br><br>RESULTS: The "Maintained" physical activity group had a significantly lower proportion of tiredness, Odds Ratio [95&#xa0;% CI]&#xa0;=&#xa0;0.57[0.39, 0.83], and joint pain, OR [95&#xa0;% CI]&#xa0;=&#xa0;0.61 [0.44, 0.84]. Even though not statistically significant, the "Decreased" activity group showed higher odds of some post-COVID symptoms.<br><br>CONCLUSION: Compared to the reference group, participants who maintained some level of physical activity during the pandemic have lower odds of presenting some post-COVID symptoms. Results highlight the importance of sustained engagement in physical activity and the need for targeted interventions to promote equitable access.},
}
@article {pmid41313894,
year = {2026},
author = {Chau, SL and Hung, IFN and Luk, TT and Chan, SSC},
title = {The impacts of long COVID and booster doses of post-infection vaccination among hospital-discharged COVID-19 survivors in Hong Kong: A retrospective observational study.},
journal = {Vaccine},
volume = {70},
number = {},
pages = {128022},
doi = {10.1016/j.vaccine.2025.128022},
pmid = {41313894},
issn = {1873-2518},
mesh = {Humans ; Male ; Female ; Middle Aged ; Hong Kong/epidemiology ; *COVID-19/epidemiology/prevention &amp; control ; Retrospective Studies ; Adult ; *Immunization, Secondary ; Quality of Life ; *COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2/immunology ; Aged ; Vaccination ; Survivors ; Risk Factors ; Prevalence ; Young Adult ; },
abstract = {BACKGROUND: This study examined the prevalence of long COVID, risk factors, vaccination status, and health-related quality of life in hospital-discharged individuals with a history of COVID-19 infection in Hong Kong.<br><br>METHODS: This is a retrospective observational study. A convenience sampling was used to recruit individuals with a history of COVID-19 infection from a university teaching hospital in Hong Kong. 717 out of 1771 individuals aged 18&#xa0;years or above with COVID-19 infection (confirmed by polymerase chain reaction/rapid antigen test) and hospitalized during the COVID-19 outbreak completed the telephone follow-up between January 2023 and March 2025. The prevalence of long COVID (defined by the WHO), risk factors, vaccination status, and health-related quality of life were analyzed. The proportions were weighted by the sex and age distribution of Hong Kong adults in 2023.<br><br>RESULTS: The mean age of participants was 46.8&#xa0;years (&#xb1;17.4), and 67.4&#xa0;% were men. The most prevalent long COVID symptoms were shortness of breath (10.8&#xa0;%), persistent fatigue (9.8&#xa0;%), forgetfulness (9.5&#xa0;%), and persistent dry cough (4.3&#xa0;%). 52.3&#xa0;% of participants received three vaccine doses after contracting COVID-19, and 71.3&#xa0;% of them received BioNTech. Participants who experienced shortness of breath, persistent fatigue, and forgetfulness had poorer health-related quality of life, as indicated by lower scores on the EuroQol-visual analog scales and the Physical and Mental Component Scores of the VR-12 (all P&#xa0;<&#xa0;0.05). Participants who received booster doses (at least three doses) were associated with lower odds of experiencing long COVID symptoms, including shortness of breath, persistent fatigue, forgetfulness, and persistent dry cough (all P&#xa0;<&#xa0;0.05).<br><br>CONCLUSIONS: The prevalence of long COVID was low among the hospital-discharged individuals, and booster doses of post-infection vaccination might reduce the risk of experiencing these symptoms. Further investigation is needed to examine the underlying mechanisms of long COVID and how these risks can be mitigated.},
}
@article {pmid41312347,
year = {2025},
author = {Singh, AK and Kumar, K and Singh, M and Jagawat, T and Nathiya, D and Singh Tomar, B and Jagawat, S and Jimenez, M and Lopez, M and Miller, J and Koralnik, IJ},
title = {Neuropsychiatric manifestations of Long COVID in India: a persistent problem 2.5 years after disease onset.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1704801},
pmid = {41312347},
issn = {1664-2295},
abstract = {BACKGROUND: Long COVID, also called post-acute sequelae of SARS-CoV-2 infection (PASC), is a multi-system syndrome affecting millions of people worldwide. Neuropsychiatric manifestations of Long COVID are particularly debilitating; however, they have not been reported in detail from India.<br><br>METHODS: This cross-sectional study compared the demographics, comorbidities, symptoms, and neuropsychiatric profiles of patients with Long COVID symptoms that began within 3&#x202f;months of the initial SARS-CoV-2 infection and persisted for approximately 2.5&#x202f;years at the time of evaluation. The study was conducted at NIMS University (Jaipur, Rajasthan, India).<br><br>RESULTS: Of 1,085 participants, 521 had COVID-19 pneumonia requiring hospitalization, while 564 had a mild initial respiratory presentation and were never hospitalized. On average 2.5&#x202f;years after acute infection, our principal finding is that Long COVID differs based on initial disease severity. Post-hospitalization patients were older than the non-hospitalized group (43.24 vs. 36.15&#x202f;years; p&#x202f;<&#x202f;0.0001), had a higher body-mass index, and a more frequent prior history of lung disease (7.7% vs. 2.7%; p&#x202f;<&#x202f;0.001). Overall, 69.6% of participants had at least one neurologic symptom, including myalgia (18.5%), dizziness (17.3%), headache (16.6%), pain (15.7%), anosmia (13.3%), brain fog (9.4%), numbness (6.0%), tinnitus (5.5%), and dysgeusia (3.7%), with only dizziness being more frequent in the post-hospitalization than the non-hospitalized group (20.3% vs. 14.5%; p&#x202f;=&#x202f;0.012). Conversely, non-hospitalized patients had more frequent fatigue (23.2% vs. 6.0%; p&#x202f;<&#x202f;0.0001), sleep problems (18.4% vs. 7.7%; p&#x202f;<&#x202f;0.0001), chest pain (8.2% vs. 2.9%; p&#x202f;<&#x202f;0.0001), and gastrointestinal symptoms (7.8% vs. 2.9%; p&#x202f;<&#x202f;0.0001), while post-hospitalization patients more frequently complained of shortness of breath (9.6% vs. 2.7%; p&#x202f;<&#x202f;0.0001). Overall, 4.9% of participants had cognitive dysfunction on the MMSE test, while 10.4% suffered from stress, and 12.7 and 9.2% had anxiety and depression symptoms, respectively, on DASS assessment, without significant differences between the two groups.<br><br>CONCLUSION: Our study highlights differences in demographics and clinical presentation of Long COVID between post-hospitalization and non-hospitalized individuals in India. The high frequency of neurologic manifestations 2.5&#x202f;years after disease onset underscores the need for early detection and targeted interventions.},
}
@article {pmid41309532,
year = {2025},
author = {Shakib, SH and Antimisiaris, D},
title = {Analysis of polypharmacy in older adults pre- and post-COVID-19.},
journal = {Expert review of clinical pharmacology},
volume = {18},
number = {11},
pages = {945-956},
doi = {10.1080/17512433.2025.2596347},
pmid = {41309532},
issn = {1751-2441},
mesh = {Humans ; *Polypharmacy ; Aged ; Female ; *COVID-19/epidemiology/diagnosis/complications ; Male ; Aged, 80 and over ; Middle Aged ; Age Factors ; },
abstract = {BACKGROUND: Increased diagnoses burden is a characteristic of post-COVID sequelae. Concomitant increased polypharmacy burden is a consequence yet there are few publications on the topic. The aim of this report is to help characterize post-COVID polypharmacy in older adults.<br><br>RESEARCH DESIGN AND METHODS: Using data from a large health system, pre- and post-COVID disease and medication burden was analyzed. Patients aged 61 years and older who were diagnosed with COVID-19 during the early variant period (March 2020-December 2021), before widespread vaccination, were followed through December 2024. Within-person difference was tested. Multiple linear regression determined predictive post-COVID increases in clinical burden. Qualitative characterization was supported by multidisciplinary literature review.<br><br>RESULTS: In patients &#x2265;61&#x2009;years, the mean increase in diagnoses and medications per post-COVID patient was 7.37 and 13.23, respectively. The largest increase in diagnoses was seen in patients aged 71-80 and people of Black race. The largest increase in medications was in patients aged 81-90 and females. Each additional pre-covid diagnosis and medication was associated with a 0.10 unit, and 0.12 unit increase, respectively, post-COVID-19.<br><br>CONCLUSIONS: Each pre-COVID diagnoses and medication were associated with quantifiable increase post-COVID, with higher risk with advanced age, Black race and female gender. Single health system data may inhibit generalizability of our findings. Clinicians should be vigilant and prepared to manage post-COVID-19 polypharmacy.},
}
@article {pmid41305454,
year = {2025},
author = {Miftahof, J and Bernauer, B and Tan, CS},
title = {Neurological Manifestations of SARS-CoV-2.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
pmid = {41305454},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; Animals ; *SARS-CoV-2/pathogenicity ; Disease Models, Animal ; Brain/virology/pathology ; *Nervous System Diseases/virology/pathology/etiology ; Central Nervous System/virology/pathology ; },
abstract = {Neurocognitive symptoms have emerged as notable sequelae of SARS-CoV-2 infection (COVID-19). Although primarily a respiratory virus, SARS-CoV-2 has been associated with central nervous system (CNS) changes observed in both clinical and experimental settings. To better understand these effects and their pathological mechanisms, we conducted a systematic literature search of published studies and employed a qualitative, analytical approach to identify and synthesize key findings from peer-reviewed studies, including large-scale retrospective clinical cohorts, human autopsy reports, animal models (murine, non-human primate), and in vitro brain organoid systems. While viral components were detected in post mortem central nervous system tissues, COVID-19 neuropathology appears to stem primarily from immune-mediated inflammation and vascular injury rather than direct CNS infection. Persistent glial activation and BBB disruption may underlie the long-term neurological symptoms reported in long COVID-19. Although animal models offer mechanistic insight, species-specific differences necessitate cautious extrapolation to human pathology. Further investigation into the chronic effects of SARS-CoV-2 on the brain is essential to guide long-term clinical management and therapeutic development.},
}
@article {pmid41305428,
year = {2025},
author = {Chiang, KC and Chiu, CEN and Altaf, M and Cheng, MTK and Gupta, RK},
title = {Mechanisms of Cell-Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
pmid = {41305428},
issn = {1999-4915},
mesh = {Humans ; *SARS-CoV-2/immunology/physiology/pathogenicity/genetics ; *COVID-19/transmission/immunology/virology ; *Immune Evasion ; Cell Fusion ; *Virus Internalization ; Giant Cells/virology ; Animals ; Antibodies, Neutralizing/immunology ; },
abstract = {Early studies on the evolution of SARS-CoV-2 revealed mutations that favored host transmission of the virus and more efficient viral entry. However, cell-free virus spread is vulnerable to host-neutralizing antibodies. As population immunity developed, mutations that confer escape from neutralization were selected. Notably, cell syncytia formation wherein an infected cell fuses with a noninfected cell is a more efficient route of transmission that bypasses humoral immunity. Cell syncytia formation has been implicated in the pathogenicity of SARS-CoV-2 infection whilst compromising host transmission due to impaired whole virion release. Therefore, understanding the mechanisms of virus-mediated cell-cell fusion will aid in identifying and targeting more pathogenic strains of SARS-CoV-2. Whilst the general kinetics of cell-cell fusion have been known for decades, the specific mechanisms by which SARS-CoV-2 induces fusion are beginning to be elucidated. This is partially due to emergence of more reliable, high throughput methods of quantifying and comparing fusion efficiency in experimental models. Moreover, the ongoing inflammatory response and emerging health burden of long COVID may point to cell-cell fusion in the pathogenesis. In this review, we synthesize current understanding of SARS-CoV-2-mediated cell-cell fusion and its consequences on immune escape, viral persistence, and the innate immune response.},
}
@article {pmid41304297,
year = {2025},
author = {An, M and Dong, X and Gao, Y and Ouyang, J and Ding, H and Zhu, Z and Bao, L and Feng, Y and Tian, W and Wang, P and Han, X and Shang, H},
title = {Immune Suppression, Preexisting Immunity, and Mutation Tendency Shaped SARS-CoV-2 Evolution in Persistent Infection.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
pmid = {41304297},
issn = {2076-2607},
support = {2023YFC3041500//the National Key Research and Development Program of China/ ; 2023-PT320-01//the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; },
abstract = {SARS-CoV-2 evolution in persistent infection, which may induce long COVID-19, is predominantly manifested in immunocompromised hosts, who act as the viral reservoirs for future outbreaks. Therefore, understanding the evolutionary mechanisms of novel variants that can evade preexisting immune responses is critical to guide public health measures and develop vaccines tailored for vulnerable populations. We used next-generation sequencing and phylogenetic methods to delineate the evolutionary and mutational profiles of SARS-CoV-2 variants using serial oropharyngeal swab samples from 5 individuals with persistent infections. Our results revealed that the intra-host evolutionary patterns of different variants varied significantly, and the evolutionary rate in 3 immunocompromised hosts was 20 times higher than in 2 other patients. These variations likely stem from differences in immune suppression status, the strength of preexisting immune responses, and the extent of error-generating mutations. There were 15 intra-host single-nucleotide variants (iSNVs) in the spike gene among at least two variants, suggesting convergent evolution. Although most new iSNVs do not reach fixation, some of them belong to lineage-defined mutations in variants of concern (VOCs) and recent variants of interest (VOIs). The observations indicate that persistent infections serve as sources for novel, potentially harmful variants, whereas the viral evolutionary dynamics are impacted by virological, immunological, and genetic factors. Thus, there is an urgent need for individualized monitoring and management of immunocompromised hosts to prevent outbreaks caused by the viral seeds generated from them and to study viral factors associated with post-acute COVID-19 sequelae.},
}
@article {pmid41304256,
year = {2025},
author = {Mateescu, DM and Ilie, AC and Cotet, I and Guse, C and Muresan, CO and Pah, AM and Badalica-Petrescu, M and Iurciuc, S and Craciun, ML and Avram, A and Margan, MM and Enache, A},
title = {Gut Microbiome Dysbiosis in COVID-19: A Systematic Review and Meta-Analysis of Diversity Indices, Taxa Alterations, and Mortality Risk.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
pmid = {41304256},
issn = {2076-2607},
support = {"Victor Babes" University of Medicine and Pharmacy Timisoara//"Victor Babes" University of Medicine and Pharmacy Timisoara/ ; },
abstract = {COVID-19 is associated with gut microbiome alterations that may influence disease outcomes through immune and inflammatory pathways. This systematic review and meta-analysis evaluated global evidence on gut dysbiosis in COVID-19. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to 5 October 2025 (PROSPERO CRD420251160970). Alpha-diversity indices and microbial taxa log-fold changes (logFC) were analyzed using random-effects models. The pooled standardized mean difference (SMD) for the Shannon index was -0.69 (95% CI -0.84 to -0.54; I[2] = 42%), confirming reduced microbial diversity. Faecalibacterium prausnitzii showed a significant pooled depletion (logFC = -1.24; 95% CI -1.68 to -0.80; k = 10; I[2] = 74%), while Enterococcus spp. was increased (logFC = 1.45; 95% CI 1.12-1.78). Egger's test did not suggest publication bias (p = 0.32). Gut dysbiosis was consistently associated with reduced microbial diversity and enrichment of pathogenic taxa, correlating with increased disease severity and mortality (HR = 1.67). These findings highlight the potential of microbiome profiling as a prognostic tool in COVID-19, although clinical translation requires further validation.},
}
@article {pmid41304215,
year = {2025},
author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV},
title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
pmid = {41304215},
issn = {2076-2607},
support = {DPI/BCE n&#xba; 01/2025//University of Brasilia/ ; FAPDF n&#xba; 09/2023//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; },
abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.},
}
@article {pmid41303228,
year = {2025},
author = {Al-Zamil, M and Kulikova, NG and Zalozhnev, DM and Shnayder, NA and Petrova, MM and Garganeeva, NP and Zhukova, NG and Tutinina, OV and Naprienko, MV and Smekalkina, LV},
title = {Using the International Index of Erectile Function-15 in Comparative Analysis Between Transcutaneous Electrical Nerve Stimulation of the Pudendal Nerve and Low-Level Laser Therapy in the Treatment of Erectile Dysfunction After COVID-19.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41303228},
issn = {2077-0383},
abstract = {Background: Erectile dysfunction (ED) is one of the manifestations of long COVID-19 and in most cases has an endothelial and neurogenic nature. Many experimental and clinical investigations have revealed the high efficacy of transcutaneous electrical nerve stimulation (TENS) of the pudendal nerve and low-level laser therapy (LLLT) in the treatment of ED. Purpose: To compare LLLT and TENS, and investigate the dynamics of their efficacy when combined in the treatment of patients with post-COVID-19 ED using the International Index of Erectile Function-15 (IIEF-15). Materials and Methods: This interventional, randomized controlled trial enrolled 82 patients with ED following COVID-19. All patients had their first ED diagnosis after COVID-19 within one month of the onset of respiratory symptoms. The duration of patients' ED was not less than six months, but less than one year. Patients were divided into four groups, one of which received sham LLLT and TENS (n = 20). The remaining patients underwent effective treatment using LLLT (n = 21), TENS (n = 21), and combined LLLT and TENS (n = 20). To study the effectiveness of the treatment, IIEF-15 and an assessment of tactile sensation in the genital area before and after the treatment, as well as 3 months after the end of the treatment, were used. Results: Both LLLT and TENS had a significant effect in improving erectile function, of 38% (p ≤ 0.01) and 27% (p ≤ 0.01), respectively. The improvement in erectile function after LLLT was higher than after TENS by 8.2% (p ≤ 0.05), but the combination of these methods exceeds the result of using LLLT alone by 20% (p ≤ 0.01). The reduction in hypoesthesia after LLLT did not exceed 17.4% (p ≤ 0.05). However, after TENS, the reduction in hypoesthesia reached 48.7% (p ≤ 0.01), and with a combination of the two methods, it reached 60.9% (p ≤ 0.01). Treatment outcomes in LLLT, TENS, and LLLT + TENS groups were stable for 3 months. Conclusions: According to IIEF-15 dynamics, LLLT and TENS are both very beneficial in treatment of post-COVID-19 ED, with LLLT showing a moderately better outcome than TENS. LLLT and TENS were found to have significant positive therapeutic effects on orgasm, sexual desire, and sexual satisfaction, among other aspects of sexual function. Nevertheless, the combination of LLLT and TENS proved to be much more successful in enhancing all IIEF domains, expanding the therapeutic effect spectrum, and improving the TENS effect following LLLT application. Only after TENS did genital hypoesthesia reliably regress, and the effect was amplified when TENS and LLLT were combined.},
}
@article {pmid41303176,
year = {2025},
author = {Olarinde, F and Nunes-Silva, A and Sanchez-Ramirez, DC and Molgat-Seon, Y and Villar, R},
title = {Using Active Standing Orthostatic Stress Test to Assess Physiological Responses in Individuals with Long COVID: A Systematic Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41303176},
issn = {2077-0383},
abstract = {Background/Objectives: Individuals experiencing long COVID (LC) frequently report orthostatic intolerance symptoms, which may be linked to autonomic and cardiovascular dysfunction. The active standing test provides a simple, clinically relevant means to assess these impairments. This systematic review aims to determine the use of the active standing orthostatic stress test in evaluating cardiovascular, autonomic, and respiratory responses in people experiencing LC. Methods: A systematic search, according to PRISMA guidelines, was conducted in PubMed, MEDLINE, EMBASE, CINAHL, and Scopus for articles published between 2020 and 2025. This study was registered in PROSPERO CRD-42024615872. Studies were included if they used the active standing test, enrolled adults (≥18 years), included both long COVID and healthy control groups, used continuous beat-to-beat measurements, and reported physiological outcomes. Risk of bias was assessed using the nine-point Newcastle-Ottawa Scale. Results: Three studies (216 participants experiencing LC and 186 controls) met the inclusion criteria. Across studies, LC individuals consistently exhibited elevated heart rate in both supine and standing positions. However, blood pressure findings were more variable: only one study reported 13% of participants met orthostatic hypotension criteria, while another found significant increases in diastolic blood pressure during standing. Long COVID groups also showed reduced heart rate variability compared to controls. Conclusions: Individuals experiencing LC show elevated heart rate and impaired autonomic function during active standing, with subgroup-specific blood pressure changes. These alterations may contribute to dizziness, fatigue, and reduced activity tolerance. Incorporating active standing into clinical assessment could aid early identification of autonomic dysfunction and inform rehabilitation strategies, though more research is urgently needed.},
}
@article {pmid41302967,
year = {2025},
author = {Alghamdi, F and Meertens, R and Obotiba, AD and Harries, LW and Appleby, S and Mokbel, K and Knapp, KM and Strain, WD},
title = {Assessment of Health-Related Quality of Life and Biomarkers in Long COVID: A 12-Month Longitudinal Feasibility Cohort.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41302967},
issn = {2077-0383},
support = {part of PhD project//Qassim University/ ; },
abstract = {Background/Objectives: Long COVID (LC) causes persistent symptoms, including fatigue, musculoskeletal (MSK) pain, and a lower quality of life. It is hypothesised that chronic low-grade inflammation in LC could impact bone, joints, and muscle microcirculation, but evidence is limited. Our aim is to assess health-related quality of life (HRQoL) and circulating inflammation, bone turnover markers (BTM), and vitamin D in LC individuals to explore their potential association with MSK function. Methods: Prospective longitudinal cohort; LC n = 45, well-recovered (WR) n = 40; 12 ± 2 months follow-up. Baseline and follow-up assessments included evaluations of HRQoL and pain-rating questionnaires, and blood analysis of inflammatory and bone turnover markers (BTM). Results: More females were in the LC group. LC reported significantly lower HRQoL compared to WR, with no change over 12 months. LC had higher vitamin D levels at baseline, median 29.46 ng/mL (23.75; 35.06) compared to WR 20.36 ng/mL (15.995; 27.65) (p = 0.0021). Both groups experienced significant increases in vitamin D after 12 months: WR median from 21.4 ng/mL (16.34; 27.89) to 29.58 ng/mL (25.33; 41.74), (p =< 0.001) and LC median from 32.695 ng/mL (23.665; 35.1) to 35.89 ng/mL (30.1; 41.2), (p = 0.0023). Pain rating showed LC also experienced more hand pain at baseline median 1 (0; 5), (p = 0.003). There were no differences between groups in BTM or cytokines over time. Conclusions: This feasibility cohort showed that LC is associated with a reduction in HRQoL and joint symptoms; however, no significant changes were observed in the inflammatory markers, indicating the need for ongoing monitoring. Future studies should explore MSK, muscle function via imaging, and ways to enhance musculoskeletal health and well-being.},
}
@article {pmid41302639,
year = {2025},
author = {Perestiuk, V and Sverstyuk, A and Kosovska, T and Volianska, L and Boyarchuk, O},
title = {A Predictive Model for the Development of Long COVID in Children.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
pmid = {41302639},
issn = {1660-4601},
support = {0123U100301//Ministry of Health of Ukraine/ ; },
mesh = {Humans ; Child ; *COVID-19/epidemiology/complications ; Child, Preschool ; Infant ; Male ; Female ; Adolescent ; Cross-Sectional Studies ; Risk Factors ; SARS-CoV-2 ; *Models, Theoretical ; },
abstract = {BACKGROUND/OBJECTIVES: Machine learning is an extremely important issue, considering the potential to prevent the onset of long-term complications from coronavirus disease or to ensure timely detection and effective treatment. The aim of our study was to develop an algorithm and mathematical model to predict the risk of developing long COVID in children who have had acute SARS-CoV-2 viral infection, taking into account a wide range of demographic, clinical, and laboratory parameters.<br><br>METHODS: We conducted a cross-sectional study involving 305 pediatric patients aged from 1 month to 18 years who had recovered from acute SARS-CoV-2 infection. To perform a detailed analysis of the factors influencing the development of long-term consequences of coronavirus disease in children, two models were created. The first model included basic demographic and clinical characteristics of the acute SARS-CoV-2 infection, as well as serum levels of vitamin D and zinc for all patients from both groups. The second model, in addition to the aforementioned parameters, also incorporated laboratory test results and included only hospitalized patients.<br><br>RESULTS: Among 265 children, 138 patients (52.0%) developed long COVID, and the remaining 127 (48.0%) fully recovered. We included 36 risk factors of developing long COVID in children (DLCC) in model 1, including non-hospitalized patients, and 58 predictors in model 2, excluding them. These included demographic characteristics of the children, major comorbid conditions, main symptoms and course of acute SARS-CoV-2 infection, and main parameters of complete blood count and coagulation profile. In the first model, which accounted for non-hospitalized patients, multivariate regression analysis identified obesity, a history of allergic disorders, and serum vitamin D deficiency as significant predictors of long COVID development. In the second model, limited to hospitalized patients, significant risk factors for long-term sequelae of acute SARS-CoV-2 infection included fever and the presence of &#x2265;3 symptoms during the acute phase, a history of allergic conditions, thrombocytosis, neutrophilia, and altered prothrombin time, as determined by multivariate regression analysis. To assess the acceptability of the model as a whole, an ANOVA analysis was performed. Based on this method, it can be concluded that the model for predicting the risk of developing long COVID in children is highly acceptable, since the significance level is p < 0.001, and the model itself will perform better than a simple prediction using average values.<br><br>CONCLUSIONS: The results of multivariate regression analysis demonstrated that the presence of a burdened comorbid background-specifically obesity and allergic pathology-fever during the acute phase of the disease or the presence of three or more symptoms, as well as laboratory abnormalities including thrombocytosis, neutrophilia, alterations in prothrombin time (either shortened or prolonged), and reduced serum vitamin D levels, are predictors of long COVID development among pediatric patients.},
}
@article {pmid41302566,
year = {2025},
author = {Sui, SX and Yu, L},
title = {Patient and Professional Perspectives on Long COVID: A Systematic Literature Review and Meta-Synthesis.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
pmid = {41302566},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/psychology ; *Health Personnel/psychology ; SARS-CoV-2 ; Qualitative Research ; },
abstract = {BACKGROUND: Post-COVID-19 condition ('long COVID') involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, recovery, and service use. We synthesised perspectives from people living with long COVID and healthcare professionals to inform service design and policy.<br><br>METHODS: We conducted a systematic review and qualitative meta-synthesis. MEDLINE, Embase, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies published between 1 January 2020 and 19 August 2025. Eligible studies reported qualitative data from adults with long COVID (&#x2265;12 weeks after acute infection) and/or healthcare professionals in any setting. We excluded non-qualitative, non-primary, or non-English reports. Two reviewers independently screened, extracted, and appraised studies using the Critical Appraisal Skills Programme checklist. Data were synthesised thematically. The protocol was registered with the Open Science Framework.<br><br>FINDINGS: Of 1544 records screened, 49 studies met the inclusion criteria: 41 involving patients, two involving professionals, and six involving both. Eight patient themes (including symptom burden, identity disruption and stigma) and four professional themes (including recognition, care coordination and holistic care models) were identified. Recognition emerged as a cross-cutting mechanism: validation and consistent pacing guidance facilitated engagement and safer activity, whereas invalidation and inconsistent advice were associated with distress, avoidance, and disengagement. Trajectories showed gradual expansion of multidisciplinary care models, but major capacity and equity gaps persisted. Most studies had low methodological concerns, although heterogeneity in populations and settings was substantial.<br><br>INTERPRETATION: Long COVID is a chronic, biological condition that also intersects with social and psychological dimensions, and may present with episodic, continuous, or progressive trajectories. Healthcare services must prioritise early validation, provide consistent pacing and relapse prevention guidance, expand access to multidisciplinary and peer-supported rehabilitation, integrate mental healthcare, strengthen coordinated pathways, and support graded return to work. Explicit attention to equity is required to avoid widening disparities.},
}
@article {pmid41301920,
year = {2025},
author = {Knauer, TS and Mardin, CY and Rech, J and Michelson, G and Stog, A and Zott, J and Steußloff, F and Güttes, M and Sarmiento, H and Ilgner, M and Jakobi, M and Hohberger, B and Schottenhamml, J},
title = {Evaluation of Stereopsis Performance, Gaze Direction and Pupil Diameter in Post-COVID Syndrome Using Machine Learning.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301920},
issn = {2227-9059},
support = {2490-PC-2021-V14//Bayerisches Landesamt f&#xfc;r Gesundheit und Lebensmittelsicherheit/ ; GRK 2504/1//Deutsche Forschungsgemeinschaft/ ; 01EO2105//Bundesministerium f&#xfc;r Forschung, Technologie und Raumfahrt/ ; },
abstract = {Background/Objectives: Post-COVID syndrome (PCS) encompasses symptoms that persist for at least 12 weeks after the onset of a COVID-19 infection and cannot be explained by other causes. The most common symptoms are fatigue, cognitive impairments, and physical limitations. The objective diagnosis of PCS is still challenging, as specific biomarkers are lacking. One possibility to measure cognitive impairment is the virtual-reality-oculomotor-test-system (VR-OTS, Talkingeyes &amp; More, Germany). It shows stereoscopic stimuli in a VR-environment to the test person. While working on the visual tasks, many features are recorded. These features can be categorized into three groups: stereopsis performance, gaze direction, and pupil diameter. The aim of this study was to investigate which of these three feature groups is best to distinguish patients with PCS from a healthy control group. Methods: In total, 429 patients with PCS were recruited within the disCOVer 1.0 and disCOVer 2.0 study at the Department of Ophthalmology, Universitätsklinikum (Erlangen, Germany). All patients received VR-OTS measurements. From these measurements, a total of 95 features were extracted, which can be categorized into three groups: gaze direction, pupil diameter, and stereopsis performance. In the first step, support vector machines (SVMs) were trained on these different feature sets and evaluated using the area under receiver operating characteristic (AUROC) as the evaluation metric. In the second step, the same procedure was repeated with each feature independently to investigate which were most the predictive per group. Results: The SVM using the pupil diameter features yielded an AUROC of 0.73, the one using the gaze direction features resulted in an AUROC of 0.68. and the stereopsis performance features produced an AUROC of 0.66. The SVM using all VR-OTS data showed an AUROC of 0.68. For the single features, the index of pupillary activity (IPA) showed the best discrimination. Moreover, all features that were evaluated at different difficulties showed the same pattern-that the more difficult test proved to be more predictive. Conclusions: The study showed that VR-OTS can distinguish between patients with PCS and healthy control probands. Since different features showed a better performance than others, it makes sense for further studies to use a subset of the available features for further analysis.},
}
@article {pmid41301889,
year = {2025},
author = {Ivanovska, M and Homadi, MS and Angelova, G and Taskov, H and Murdjeva, M},
title = {Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301889},
issn = {2227-9059},
abstract = {Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.},
}
@article {pmid41301758,
year = {2025},
author = {García-Onrubia, J and Vazirani, R and Feltes, G and Sánchez-Del Hoyo, R and Viana-Llamas, MC and Raposeiras-Roubín, S and Romero, R and Alfonso-Rodríguez, E and Uribarri, A and Santoro, F and Becerra-Muñoz, V and Pepe, M and Castro-Mejía, AF and Signes-Costa, J and Gonzalez, A and Marín, F and Lopez-País, J and Cerrato, E and Vázquez-Cancela, O and Espejo-Paeres, C and López Masjuan, &#xc1; and Velicki, L and El-Battrawy, I and Ramakrishna, H and Fernandez-Ortiz, A and Nuñez-Gil, IJ},
title = {The Long-Term Outcomes of Corticosteroid Use in COVID-19 Patients with Cardiovascular Disease: A Propensity-Matched Analysis from the Multi-Center International Prospective Registry (HOPE-2).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301758},
issn = {2227-9059},
abstract = {Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4-14] and 11 days [IQR: 7-18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients.},
}
@article {pmid41301729,
year = {2025},
author = {Quach, TC and Wilson, A and Sum-Ping, O and Lomba, S and Geng, LN and Shafer, R and Miglis, MG and Yang, PC and Grossman, L and Ricciardiello, G and Bonilla, H},
title = {Can Low Cortisol Predict Long COVID? A Controversial Issue.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301729},
issn = {2227-9059},
abstract = {Cortisol dysregulation has been proposed as a biomarker of long COVID (LC), but findings remain inconsistent. Prior reports suggested low cortisol levels in LC, yet collection times and study designs varied substantially. To evaluate morning serum cortisol distributions in an independent LC cohort, accounting for circadian timing and sleep patterns, we performed a retrospective cross-sectional study of consecutive adults seen at the Stanford Long COVID Clinic between 14 February 2022 and 31 July 2024 (IRB #62996). Eligible participants had confirmed SARS-CoV-2 infection, symptoms persisting ≥3 months per NASEM criteria, completion of the Alliance Sleep Questionnaire (ASQ), and a morning serum cortisol measured using the Roche Elecsys[®] Cortisol II assay. Analyses were restricted to collections between 05:00-10:00, categorized as early morning peak (EMP: 05:00-08:00) or mid-morning (MMP: 08:01-10:00). Cortisol was classified as low (<6.2 μg/dL), normal (6.2-19.4 μg/dL), or elevated (>19.4 μg/dL). Among 86 LC patients (69.8% female; mean age 45.4 ± 12.9 years), the mean serum cortisol level was 15.67 ± 6.76 μg/dL. Overall, 62.8% of patients had cortisol within the reference range, 36.0% had elevated levels, and only 1.2% (n = 1) had a low value. Cortisol distributions were comparable across the EMP and MMP collection windows, with no statistically significant differences observed by sleep alignment. Inflammatory markers, including CRP and D-dimer, were largely within reference ranges across all cortisol strata. Contrary to earlier reports, low morning cortisol was rare in this LC cohort; most values were normal or elevated. Findings underscore the importance of circadian timing when interpreting cortisol in LC and highlight the need for prospective studies with serial measurements to determine biomarker utility.},
}
@article {pmid41300187,
year = {2025},
author = {Pour Mohammadi, S and Etesamipour, R and Mercado Romero, F and Noroozi Fashkhami, M and Peláez, I},
title = {Physical Symptoms and Neurocognitive Complaints in Long COVID: Associations with Gender, Age, Education, and Clinical Factors.},
journal = {Brain sciences},
volume = {15},
number = {11},
pages = {},
pmid = {41300187},
issn = {2076-3425},
abstract = {Long COVID is frequently accompanied by neurocognitive complaints, yet the combined effects of demographic and clinical factors remain unclear. This study examined individuals six months after their most recent SARS-CoV-2 infection using a Demographic/Infection-History form, a Physical and Neurocognitive Symptom Checklist (binary), and the Post-COVID Cognitive Impairment Scale (memory, attention; 5-point Likert). Participants were recruited through convenience sampling from multiple community and online sources. Inclusion criteria required confirmed prior COVID-19 infection, self-perceived or clinically documented Long COVID symptoms, and no history of neurological or severe psychiatric disorders. The final sample consisted of 212 participants (mean age = 39.7 years, SD = 10.5), of whom 67.9% were female, and most held a master's (35.4%) or bachelor's (28.3%) degree. Difficulties with retaining new information (57.8%) and concentrating (52.1%) were the most frequent neurocognitive complaints, while severe fatigue after mild activity (23.2%) and chronic fatigue (22.7%) were the most common physical symptoms. Confusion and decision-making difficulty were more frequent among younger participants; women reported greater difficulty retaining new information, and difficulty concentrating varied by education level. A multivariable regression model explained 7% of the variance in total cognitive complaints, identifying education level (β = -0.18, p < 0.01) and number of physical symptoms (β = 0.19, p < 0.01) as significant predictors. Higher educational attainment was associated with fewer cognitive complaints, whereas a greater burden of physical symptoms predicted higher complaint scores. Persistent cognitive difficulties in Long COVID appear closely related to physical symptom burden and protective factors such as education, rather than to infection frequency or sensory dysfunction duration. Findings highlight the need for routine cognitive screening, fatigue-focused management, and longitudinal multimodal research to elucidate underlying mechanisms and recovery pathways.},
}
@article {pmid41299665,
year = {2025},
author = {Dalle Carbonare, L and Minoia, A and Zouari, S and Braggio, M and Cominacini, M and Gaglio, SC and Piritore, FC and Lorenzi, P and Meneghel, M and Dervishi, K and Corsi, A and Pedrinolla, A and Giuriato, G and Fiore, A and Celesia, A and Guerricchio, L and Venturelli, M and Schena, F and Donadelli, M and Mottes, M and Romanelli, MG and Perduca, M and Guardavaccaro, D and Crisafulli, E and Zipeto, D and Barile, L and Valenti, MT},
title = {Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {508},
pmid = {41299665},
issn = {1478-811X},
support = {Excellence Project 2023-2027 of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona//MUR/ ; PRIN 2022 - Projects of Relevant National Interest, funded by the European Union - NextGenerationEU, PNRR, Mission 4, Component 2, Investment 1.1, project Title "Fine definition of systemic and mucosal response in SARS-CoV-2 vaccinated subjects" - CUP code B53D23003410006.//MUR/ ; },
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *MicroRNAs/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism ; *COVID-19/metabolism/pathology ; *Core Binding Factor Alpha 1 Subunit/metabolism/genetics ; Human Umbilical Vein Endothelial Cells/metabolism ; Signal Transduction ; SARS-CoV-2 ; Female ; Male ; Mesenchymal Stem Cells/metabolism ; Stress, Physiological ; },
abstract = {BACKGROUND: Subjects with Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), experience a wide range of symptoms, including fatigue and respiratory disturbances, affecting their quality of life. Despite the increasing prevalence of Long COVID, the underlying pathogenic mechanisms remain poorly understood. Extracellular vesicles (EVs) are known to be involved in various processes, such as tissue repair and the transmission of viral particles. However, the specific characteristics and functional roles of EVs derived- from patients with Long COVID (LC-EVs) are poorly characterized.<br><br>METHODS: To uncover systemic mechanisms underlying Long COVID, we performed a comprehensive characterization of patient-derived extracellular vesicles (EVs) via Nanoparticle Tracking analysis (NTA), Atomic Force Microscopy (AFM), Transmission Electron Microscope (TEM) and flow cytometry. These EVs were applied to lung cells, Mesenchymal Stem Cell (MSCs), Human Umbilical Vein Endothelial Cells (HUVECs) and Aortic Smooth Muscle Cells (ASMCs), revealing stress responses through SESN1, SESN2, and p53 activation. We further assessed mitochondrial respiration to evaluate metabolic dysfunction, and conducted targeted transfection experiments to dissect the molecular pathways involved, shedding light on EV-driven cellular reprogramming.<br><br>RESULTS: Thus, we observed that Long COVID (LC) patients experienced breathlessness and leg discomfort during exertion. Our data highlighted that LC-EVs induce aberrant RUNX2 expression and activate the p53/p21 pathway in lung cells as well stress responses. Additionally, LC-EVs impair mitochondrial function and cellular adaptability under metabolic stress, reducing maximal respiration and ATP production at high cell densities. Protein interaction analysis showed RUNX2 involvement in key biological processes and post-transcriptional regulation by hsa-miR-204-5p was identified. Finally, LC-EVs also activated stress pathways and increased RUNX2, SESN, p53, and p21 levels in endothelial cells, aortic smooth muscle cells, and mesenchymal stem cells.<br><br>CONCLUSIONS: In conclusions, these findings provide new insights into the role of extracellular vesicles in Long COVID, revealing their involvement in cellular stress and impaired mitochondrial function.},
}
@article {pmid41299639,
year = {2025},
author = {Gamillscheg-Müllner, P and Łaszewska, A and Hoffmann, K and Simon, J and Mayer, S},
title = {Barriers, facilitators, and the role of central coordination: understanding long COVID-19 healthcare access in a universal healthcare system.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {286},
pmid = {41299639},
issn = {0778-7367},
support = {SO68900010//Medical University of Vienna and the University of Vienna/ ; SO68900010//Medical University of Vienna and the University of Vienna/ ; SO68900010//Medical University of Vienna and the University of Vienna/ ; },
abstract = {BACKGROUND: This study comprehensively analyses healthcare access barriers and facilitators encountered by long COVID-19 patients in a universal healthcare system, including the potential role of central coordination units in alleviating the patient burden.<br><br>STUDY DESIGN: Retrospective cross-sectional long COVID-19 patient questionnaire survey.<br><br>METHODS: Data collection took place 10&#x2013;12/2024 in Austria (n&#x2009;=&#x2009;433). Conceptualized along the five steps of the &#x2018;access to care&#x2019; framework, the questionnaire covered 47 barriers and 10 facilitators derived from a previous qualitative study. Descriptive statistics, Whitney-Mann-U and t-tests, as well as linear and ordered logistic regressions were used in the statistical analysis.<br><br>RESULTS: Barriers were encountered in all access steps with the mean number of barriers considered problematic being 31.9 (SD 8.4) out of 47. The most common barriers were lacking information and the burden of self-organising one&#x2019;s treatment (perceived as problematic by over 90%), followed by the need to consult private (non-contracted) doctors due to insufficient expertise in the public sector and difficulties in treating symptoms by GPs and specialists (85%). Participants living in federal states offering central coordination encountered statistically significantly fewer barriers, perceiving a mean of 17.4 barriers (SD 9.7) as very problematic compared to 21.0 (SD 9.2). Differences were particularly pronounced regarding the availability of services within the public sector and incurred costs although the overall burden remained high. Main facilitators included family and friends and the (information) exchange with other patients.<br><br>CONCLUSIONS: Our findings have important policy and research implications beyond the Austrian context, supporting the establishment of central coordination units and research assessing the effectiveness and implementation of long COVID-19 pathways to improve patients&#x2019; healthcare access.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13690-025-01783-1.},
}
@article {pmid41295749,
year = {2025},
author = {Westman, H and Hammarström, P and Nyström, S},
title = {SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis.},
journal = {Biochemistry},
volume = {64},
number = {24},
pages = {4818-4829},
pmid = {41295749},
issn = {1520-4995},
mesh = {*Fibrinolysis ; *Spike Glycoprotein, Coronavirus/metabolism/chemistry ; *Fibrin/metabolism ; Humans ; *Amyloid/metabolism/chemistry ; *SARS-CoV-2/metabolism ; *COVID-19/metabolism/virology/blood ; Fibrinogen/metabolism ; },
abstract = {Long COVID, or postacute sequelae of COVID-19 from SARS-CoV-2 infection, is a persistent debilitating disease affecting multiple systems and organs. Long COVID pathophysiology is a complex and not fully established process. One prevailing theory is that the formation of fibrin amyloid microclots (fibrinaloids), due to SARS-CoV-2 infection, can induce persistent inflammation and capillary blockage. An association between the amyloidogenic Spike protein of SARS-CoV-2 and impaired fibrinolysis was made when it was observed that fibrin clots formed in the presence of a mixture of amyloid fibrils from the spike protein mediated resistance to plasmin lysis. Here, we use purified components from the coagulation cascade to investigate the molecular processes of impaired fibrinolysis using seven amyloidogenic SARS-COV-2 Spike peptides. Five of seven Spike amyloid fibrils appeared not to substantially interfere with the fibrinogen-fibrin-fibrinolysis process in vitro, while two spike fibrils were active in different ways. Spike601 amyloid fibrils (sequence 601-620) impaired thrombin-mediated fibrin formation by binding and sequestering fibrinogen but did not affect fibrinolysis. On the contrary, fibrin clots formed in the presence of Spike685 amyloid fibrils (sequence 685-701) exhibited a marked resistance to plasmin-mediated fibrinolysis. We conclude that Spike685 amyloid fibrils can induce dense fibrin clot networks as well as incorporate fibrin into aggregated structures that resist fibrinolysis. Our study proposes a molecular mechanism for how the Spike protein of SARS-CoV-2 could contribute to the formation of fibrinolysis-resistant microclots observed in long COVID.},
}
@article {pmid41293716,
year = {2025},
author = {Mancini, DM and Brunjes, DL and Cook, D and Soto, T and Blate, M and Quan, P and Yamazaki, T and Norweg, A and Natelson, BH},
title = {Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1669036},
pmid = {41293716},
issn = {2296-858X},
abstract = {INTRODUCTION: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience symptoms of fatigue, dyspnea, mental fog, and worsening fatigue after physical or mental efforts. Some of these patients have been found to hyperventilate. In long COVID patients, many of whom also have ME/CFS, dysfunctional breathing (DB) has been described. Whether patients with ME/CFS, independent of COVID-19, experience dysfunctional breathing is unknown, as well as how it may relate to hyperventilation.<br><br>METHODS: We performed serial 2-day cardiopulmonary exercise testing (CPET) in 57 patients with ME/CFS and 25 age- and activity-matched control participants. Peak oxygen consumption (VO2), ventilatory efficiency slope (VE/VCO2), O2 saturation, end-tidal CO2 (PetCO2), heart rate, and mean arterial blood pressure were measured in all patients during upright incremental bicycle exercise. Ventilatory patterns were reviewed using minute ventilation (VE) versus time, respiratory rate, and tidal volume versus minute ventilation graphs. Chronic hyperventilation (HV) was defined as a PETCO2 of <34&#x202f;mm Hg that persisted during low-intensity exercise. Dysfunctional breathing was characterized by a 15% increase in oscillations in minute ventilation during at least 60% of the exercise duration or by a scatterplot pattern of respiratory rate and tidal volume plotted versus minute ventilation.<br><br>RESULTS: The patients with ME/CFS had an average age of 38.6&#x202f;&#xb1;&#x202f;9.6&#x202f;years, and a mean body mass index (BMI) of 24.1&#x202f;&#xb1;&#x202f;3.4, which was comparable to the sedentary controls. All participants performed maximal exercise, achieving a respiratory exchange ratio (RER) of >1.05. For the patients with ME/CFS, peak VO2 averaged 22.3&#x202f;&#xb1;&#x202f;5.3&#x202f;mL/kg/min, which was 79&#x202f;&#xb1;&#x202f;20% of predicted and comparable to that observed in the sedentary controls (23.4&#x202f;&#xb1;&#x202f;4.6&#x202f;mL/kg/min; 81&#x202f;&#xb1;&#x202f;12%; p&#x202f;=&#x202f;NS). A total of 24 patients with ME/CFS (42.1%) met the criteria for dysfunctional breathing compared to four sedentary controls (16%) (p&#x202f;<&#x202f;0.02). In total, 18 patients with ME/CFS (32%) had hyperventilation compared to one sedentary control participant (4%) (p&#x202f;<&#x202f;0.01), and nine patients with ME/CFS had both hyperventilation and dysfunctional breathing, whereas no sedentary participant exhibited both. The patients with ME/CFS and hyperventilation had significantly higher VE/VCO2 ratios (HV+: 34.7&#x202f;&#xb1;&#x202f;7.2; HV-: 28.1&#x202f;&#xb1;&#x202f;3.8; p&#x202f;<&#x202f;0.001). A total of 15 of 18 patients with hyperventilation (83%) had either elevated VE /VCO2 ratios (n&#x202f;=&#x202f;15) or dysfunctional breathing (n&#x202f;=&#x202f;9) compared to 44% (n&#x202f;=&#x202f;17) of the 40 non-hyperventilators (p&#x202f;<&#x202f;0.01).<br><br>CONCLUSION: Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.},
}
@article {pmid41293426,
year = {2025},
author = {Sørensen, L and Agergaard, J and Nielsen, TB and Schiøttz-Christensen, B and Laursen, CH and Leth, S and Nielsen, CV and Oestergaard, LG},
title = {Construct validity of self-reported and interview-guided administration methods of the Danish version of the post-COVID-19 functional Status scale.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1690892},
pmid = {41293426},
issn = {2673-6861},
abstract = {INTRODUCTION: The Post-COVID-19 Functional Status (PCFS) scale was quickly adopted into COVID-19 research and clinical practice worldwide to monitor functional status and recovery. The scale has been translated into Danish, and three different administration methods have been employed. However, clinicians have expressed concerns about the scale's ability to capture work-related functional limitations. Therefore, the purpose of this study was to evaluate the construct validity of three different administration methods of the Danish version of the PCFS scale.<br><br>METHODS: This cross-sectional study included patients with long COVID who completed three versions of the PCFS scale: a questionnaire-based version, a flowchart-based version, and an interview-based version. The construct validity was evaluated following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines by testing predefined hypotheses that compared the PCFS scale with sick leave and EuroQoL Five-dimensions Five level (EQ-5D-5l).<br><br>RESULTS: A total of 437 patients, with a mean age 48 years, 75% female, and 59% on sick leave, were included in this study. Statistically significant differences between the three administration methods were found. Of the 234 patients on sick leave, only 50%-54% had a PCFS grade &#x2265;3 which was below our predefined hypothesis. Furthermore, correlations between the PCFS scale and EQ-5D-5l was lower than hypothesized.<br><br>CONCLUSION: None of the three administration methods effectively captured work-related functional limitations associated with being on part-time or full-time sick leave. Additionally, correlations with quality of life were lower than expected. Overall, the construct validity of the PCFS scale was only partially supported.},
}
@article {pmid41291987,
year = {2025},
author = {Rhodes, S and Tutbury, M},
title = {Suggestions for managing long Covid in primary care in Aotearoa New Zealand: a qualitative study.},
journal = {Journal of primary health care},
volume = {},
number = {},
pages = {},
doi = {10.1071/HC25143},
pmid = {41291987},
issn = {1172-6156},
abstract = {Introduction In Aotearoa New Zealand, the responsibility for management of long Covid sits with primary care. GPs are often the first point of contact for these patients in a system that is already overburdened. Globally, patient experiences of accessing support for long Covid are varied. To date, the perspectives of New Zealanders living with the condition, on how best to support their care, have not been sought. Aim The aim of this study is to explore what a long Covid service should offer from the perspectives of those living with the condition. Methods Participants were recruited via the New Zealand long haulers Facebook group and individual interviews and discussions were conducted using Zoom. These were semi-structured with a few loosely structured questions to encourage discussion. Data were analysed using Braun and Clarke's thematic analysis. Results Eighteen participants were recruited. Four themes were identified in the data: practical guidance to support the health care journey; training and collaboration between health professionals; personalised care; and opportunity for health system change. Discussion Overall, participants appeared to want interdisciplinary knowledge sharing; collaborative services with clear lines of communication and a person-centred approach to care. Many of these proposed suggestions for a long Covid clinic align with the Ministry of Health recommendations. However, to date, there is no addition support from Government to support these long Covid service recommendations.},
}
@article {pmid41286763,
year = {2025},
author = {Assavanopakun, P and Wangkawong, S and Kiratipaisarl, W and Sirikul, W and Promkutkao, T and Promkutkeo, S and Kitro, A},
title = {The hidden burden: prevalence and risk factors of long COVID among university students in Chiang Mai, Thailand.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {4123},
pmid = {41286763},
issn = {1471-2458},
support = {No.074/2566//Faculty of Medicine, Chiang Mai University/ ; },
mesh = {Humans ; Thailand/epidemiology ; Female ; *COVID-19/epidemiology ; *Students/statistics &amp; numerical data ; Male ; Cross-Sectional Studies ; Universities ; Prevalence ; Young Adult ; Risk Factors ; Adult ; Surveys and Questionnaires ; Adolescent ; COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2 ; },
abstract = {BACKGROUND: As the COVID-19 pandemic transitions to an endemic phase, long COVID symptoms following SARS-CoV-2 infection have emerged as a new global health challenge. However, its impact on university students remains underexplored. This study aimed to assess the prevalence of long COVID symptoms and identify its predictive factors.<br><br>METHODS: A cross-sectional study was conducted from February to August 2023 among Thai university students in Chiang Mai. An online questionnaire collected data on demographics, COVID-19 history, vaccination, and health status. Multivariable binary logistic regression was used to identify factors associated with long COVID.<br><br>RESULTS: A total of 997 students participated (60.5% female, mean age 20.6 years). Of these, 60.9% had received at least three COVID-19 vaccine doses, and 21.4% had received more than three mRNA vaccine doses. The prevalence of long COVID symptoms was 21.9% (n&#x2009;=&#x2009;218). Common symptoms included respiratory issues (54.6%), neurological complaints (50.4%), psychological symptoms (42.7%), and poor sleep quality (34.9%). Significant predictors of long COVID included severe initial infection (aOR&#x2009;=&#x2009;15.3; 95% CI: 5.3-44.3; p&#x2009;<&#x2009;0.001), longer illness duration (aOR&#x2009;=&#x2009;1.05; 95% CI: 1.0-1.1; p&#x2009;=&#x2009;0.031), and poor sleep quality (aOR&#x2009;=&#x2009;2.1; 95% CI: 1.4-3.1). Each additional dose of mRNA vaccine reduced the likelihood of severe outcomes by 14% (aOR&#x2009;=&#x2009;0.86; 95% CI: 0.8-1.0; p&#x2009;=&#x2009;0.044).<br><br>CONCLUSION: A minority of Thai university students reported long COVID symptoms. Vaccination, especially with multiple mRNA doses, was linked to reduced risk. Early detection and targeted support during recovery may help mitigate long-term health consequences in this group.},
}
@article {pmid41285857,
year = {2025},
author = {Green, R and Marjenberg, Z and Lip, GYH and Banerjee, A and Wisnivesky, J and Delaney, BC and Peluso, MJ and Wynberg, E and Abduljawad, S},
title = {A systematic review and meta-analysis of the impact of vaccination on prevention of long COVID.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10326},
pmid = {41285857},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/prevention &amp; control/immunology/virology/epidemiology ; *COVID-19 Vaccines/administration &amp; dosage/immunology ; Immunization, Secondary ; *SARS-CoV-2/immunology ; *Vaccination ; Odds Ratio ; },
abstract = {Long COVID affects millions worldwide and its prevention is a critical public health strategy. While prior analyses show primary vaccination prevents long COVID in subsequent infections, the effect of booster vaccination on long COVID after Omicron infections is unclear. This systematic review identifies 31 observational studies, of which 11 are suitable for pairwise meta-analyses. The pooled odds ratio (OR) of long COVID in those vaccinated (any dose) versus unvaccinated is 0.77 (95% confidence interval [CI] 0.70-0.85; p < 0.0001; 10 studies). ORs were also lower for primary course vaccination versus unvaccinated (OR 0.81; 95% CI 0.79-0.83; p < 0.0001; 3 studies), booster vaccination versus unvaccinated (OR 0.74; 95% CI 0.63-0.86; p = 0.0001; 4 studies), and booster vaccination versus primary course vaccination (OR 77; 95% CI 0.65-0.92; p = 0.0044; 3 studies). These findings indicate that booster vaccination can provide additional protection against long COVID, highlighting the importance of seasonal vaccination against new SARS-CoV-2 variants. They should, however, be interpreted cautiously, given the small number of studies and the low quality of evidence.},
}
@article {pmid41285594,
year = {2025},
author = {Lubell, J},
title = {To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!.},
journal = {Annals of family medicine},
volume = {23},
number = {6},
pages = {570-572},
pmid = {41285594},
issn = {1544-1717},
mesh = {Humans ; *Caregivers/psychology ; Female ; *Biomedical Research ; Fatigue Syndrome, Chronic/therapy/psychology ; },
abstract = {My daughter has been diagnosed with a range of chronic conditions, including Hyper-mobile Ehlers-Danlos Syndrome and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I have approached my role as caregiver in the same way I approach my day job leading social science research: reading the literature, carefully observing her condition, and developing hypotheses about her conditions and how they might be treated. I now have more than 7 years of longitudinal observation-a wealth of data-but no easy way to share with the medical research community the hypotheses these observations have engendered and my ideas about how to productively structure future research to accelerate progress toward treatments for her and others like her. In this essay, I share my thoughts on why patient and caregiver observations and hypotheses are important and how the medical research field might tap into them to make faster progress toward effective treatments for complex medical conditions.},
}
@article {pmid41283027,
year = {2025},
author = {Cousins, O and Jokela-Pansini, M and Alwan, NA and Barnard, E and Dainow, J and Dalton, C and Davies, G and Faghy, MA and Gilmour, E and Patel, I and Sherwood, O and Westerhof, L and Greenhough, B},
title = {Co-creating a social science research agenda for Long Covid.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1654488},
pmid = {41283027},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/therapy ; *Social Sciences ; Surveys and Questionnaires ; Female ; Male ; *Research ; SARS-CoV-2 ; Adult ; Middle Aged ; Health Personnel ; },
abstract = {INTRODUCTION: Our objective was to understand how social scientific research could best address the needs and concerns of patients, families, carers, healthcare professionals, academics, private and public sector professionals, and volunteers from Long Covid charities and support groups and people with lived experience of Long Covid. We worked with different stakeholders to develop a list of research priorities that particularly focused on social science as this is where our collective expertise lies, but similar methods could also be used to set research priorities in the natural sciences, medicine or the humanities.<br><br>METHODS: We used purposive sampling and conducted two online surveys. The first online survey (N&#x2009;=&#x2009;57) asked participants to identify their top five questions of concern, which resulted in a list of 253 questions. These questions were then consolidated, refined and edited down to 55 questions, categorized by topic. In the second survey (N&#x2009;=&#x2009;66), we asked participants to select and rank their top 10 questions from this refined list. The final output was a ranked list of nine questions based on those prioritized by at least 50% of the respondents.<br><br>RESULTS: Nine research questions were developed concerning (i) treatments, therapies, and strategies; (ii) financial support; (iii) repeated reinfections; (iv) training of healthcare professionals; (v) mental health impact; (vi) future of research funding; (vii) airborne transmissions of COVID-19; (viii) developing therapeutics informed by patients' experiences; and (ix) socioeconomic impacts of Long Covid. Many of the issues raised mirror those discussed in previous work in the UK and internationally, but additional novel themes emerged, underscoring the value of this collaborative approach.<br><br>CONCLUSION: Our survey revealed the value of including the voices of diverse individuals affected by Long Covid and those working in this area and highlighted priorities for social science in the field of Long Covid research.},
}
@article {pmid41282857,
year = {2025},
author = {Dunckley, N and Zhang, N and Adler, CH and Shill, HA and Mehta, S and Driver-Dunckley, E and Belden, CM and Atri, A and Choudhury, P and Kuramoto, A and Serrano, GE and Beach, TG},
title = {Post-Acute COVID-19 Effects on Diagnostic Conversion Rates And Standardized Cognitive and Motor Test Scores in a Longitudinal Study of Independent, Community-Recruited Elderly Subjects.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282857},
support = {P30 AG019610/AG/NIA NIH HHS/United States ; P30 AG072980/AG/NIA NIH HHS/United States ; },
abstract = {There is considerable concern about the long-term consequences of COVID-19 infection, generally referred to as post-acute sequelae, including declines in cognitive and motor abilities. The degree to which COVID-19 contributes additional burden to normal aging trajectories remains unclear. Additionally, the impact of COVID-19 on subjects under study for age-related neurological diseases is a potential confounder that needs definition. This study investigated whether having had a COVID-19 illness was associated with a differential decline in cognitive or motor function in older adults, utilizing data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP), a longitudinal clinicopathological study based in metropolitan Phoenix, Arizona. Subjects were included if they 1) had completed a questionnaire about their experience with COVID-19 illness 2) were classified as cognitively normal at pre-pandemic diagnostic cognitive consensus conferences and 3) had one or more subsequent diagnostic conferences between July 1, 2020 and August 30, 2025. All subjects had serial standardized research-dedicated clinical evaluations including the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale (UPDRS). Specific objectives were to compare, between those who reported having had or not having had COVID-19, rates of conversion to cognitive impairment or dementia as well as pre-pandemic and final MoCA and UPDRS motor scores. A total of 100 subjects self-reported having had COVID-19 while 71 denied having had it. Their related acute illness severity was generally mild, with only 10% having had hospital treatment and none having required ventilator support. Post-acute symptoms were also mild; only 1 subject reported having "long Covid". Both cognitive and motor performance, as measured by MoCA and UPDRS part 3 scores, declined slightly (not statistically significant) over the study period. Conversion of cognitive diagnosis from normal to impaired or dementia occurred in 26% of those having had COVID-19 and in 32% of those not having had COVID-19; the difference was not significant. All subjects diagnosed with PD at the start of the study were also diagnosed with PD at the end of the study; no subjects converted from not having to having probable PD. Logistic regression analysis indicated that subjects' report of having had COVID-19 was not significantly associated with conversion to cognitive impairment or dementia while greater age, male sex, possession of one or more apolipoprotein E- ɛ4 alleles, and a diagnosis of probable PD all conferred a significantly greater likelihood of conversion. The results suggest that having a mild COVID-19 illness is not associated with greater declines on cognitive or motor screening tests than would be expected from age-related changes alone. Limitations of this analysis include small sample sizes, potential misclassification of COVID-19 status, and reliance on relatively crude clinical metrics that may miss significant functional changes. Additionally, we were unable to separately assess for varying COVID-19 severity dependent on whether or not the subject had been vaccinated, the number and type of vaccinations, and the particular SARS-CoV-2 variants that were circulating at the time of illness.},
}
@article {pmid41282756,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D},
title = {Long COVID Longitudinal Symptoms Burden Clusters Within A National Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282756},
support = {UH3 AI133675/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Long COVID is clinically heterogeneous, with evolving symptom trajectories that complicate classification. Prior clustering studies often rely on Electronic Health Records data, risking underreporting. We used longitudinal, community-based data to characterize symptom clusters and risk factors.<br><br>METHODS: We analyzed CHASING COVID Cohort participants with confirmed SARS-CoV-2 infection between December 2020 and December 2022, &#x2265;12 months of follow-up, and long COVID (&#x2265;1 new symptom and concurrent activity limitation 3-12 months post-infection, both absent pre-infection). The infection in this window was the index infection; those with pre-index long COVID were excluded. Symptoms were self-reported pre-infection and at ~3, 6, 9, and 12 months. Missing data were handled via multiple imputation by chained equations (30 datasets). Longitudinal K-means clustering was performed within each imputed dataset, with hierarchical aggregation to derive final assignments. Multivariable logistic regression (adjusting for age, sex) assessed associations of demographic, clinical, and social factors with cluster membership. Within the highest-burden cluster, hierarchical clustering identified symptom phenotypes.<br><br>RESULTS: Of 1,787 infected participants, 511 met criteria (22% &#x2265;50 years; 55% female; 60% White non-Hispanic; 54% mental health disorder; 7.2% immunodeficiency; 21% &#x2265;2 comorbidities; 30% prior infection; 24% never vaccinated pre-index). Three clusters emerged: highest, moderate, and lowest burden. The highest-burden cluster (median 6 symptoms at 6 and 9 months) was characterized by fatigue (57%-74%), concentration difficulty, post-exertional malaise, myalgia, sleep disturbance, gastrointestinal symptoms, headache, irritability, and mobility limitations (each ~46%-53%). The moderate cluster peaked at 3 symptoms (fatigue 42%); the lowest remained ~1 symptom (fatigue 24% at 12 months). Older age (aOR 2.68, 95% CI 1.59-4.53), female sex (2.36, 1.48-3.76), mental health disorder (2.65, 1.65-4.25), and immunodeficiency (4.23, 1.71-10.51) were associated with highest vs lowest burden. Within the highest-burden cluster, three phenotypes emerged: neurological/multisystemic, psychiatric/neurological, and physical/respiratory.<br><br>CONCLUSIONS: Distinct long-COVID clusters and phenotypes underscore heterogeneity and support tailored management and risk stratification.},
}
@article {pmid41282714,
year = {2025},
author = {Pearson, ML and Laraway, BJ and Elias, ER and Bilousova, G and Haendel, MA and , },
title = {Understanding Comorbidities in Hypermobile Ehlers-Danlos Syndrome: Could a Viral Infection Lead to a Diagnosis?.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282714},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; T32 AR007411/AR/NIAMS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {Hypermobile Ehlers-Danlos Syndrome (hEDS) is a complex, underdiagnosed connective tissue disorder characterized by widespread symptoms affecting multiple organ systems. Recent clinical observations suggest that individuals with hEDS may be at increased risk for persistent symptoms following COVID-19, commonly referred to as Long COVID. Using data from over 23 million patients across the United States, we examined associations between hEDS, COVID-19 infection, Long COVID, and related chronic conditions. We identified nearly 30,000 individuals with hEDS and found that the estimated prevalence was approximately 1 in 800, higher than previously recognized. While rates of COVID-19 infection were similar between patients with hEDS and matched controls, those with hEDS were significantly more likely to develop Long COVID. This risk was especially elevated among patients with hEDS with overlapping conditions commonly seen in post-viral syndromes, including autonomic dysfunction, immune dysregulation, and chronic fatigue. Specifically, individuals with postural orthostatic tachycardia, mast cell-related symptoms, or chronic fatigue syndrome had the highest rates of Long COVID. Cumulative incidence analysis revealed that many patients received an hEDS diagnosis only after a COVID-19 infection, suggesting that viral illness may exacerbate or reveal previously unrecognized symptoms. Patients with hEDS also exhibited higher odds of having additional risk factors for severe or prolonged illness, including chronic lung and autoimmune conditions, depression, and cerebrovascular disease. These findings highlight a previously unrecognized vulnerability in patients with hEDS and underscore the need for greater clinical awareness of their heightened risk for persistent post-COVID illness. Improved screening, earlier diagnosis, and integrated care pathways are urgently needed to support this complex and underserved patient population.},
}
@article {pmid41282703,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D},
title = {Effect of a Third COVID-19 Vaccine Dose on the Incidence of Long COVID Among Adults Who Completed a Primary Vaccine Series: a Target Trial Emulation in a Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282703},
support = {UH3 AI133675/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving ≥1 third dose versus completing only a primary series on 6- and 12-month long COVID incidence using a target-trial emulation in a U.S. community cohort.<br><br>METHODS: We analyzed the CHASING COVID Cohort, a prospective, community-based study of U.S. adults. Eligible participants were &#x2265;18 years, had completed a two-dose primary series, had no prior long COVID, and had no SARS-CoV-2 infection in the 3 months before time zero. Strategies compared were: receive a third dose at time zero vs. not receive a third dose during follow-up. Long COVID was defined as &#x2265;1 new symptom at or beyond 3 months post-infection with concurrent activity limitation, both absent in the prior year. Follow-up was 6 and 12 months. We used a per-protocol analog: participants were artificially censored upon deviating from their assigned strategy or lost-to-follow-up, with inverse-probability weights to address selection due to censoring and time-varying confounding. We fit weighted pooled logistic models to estimate weighted incidence, differences, and ratios at each horizon.<br><br>RESULTS: Across 16 sequential trials (18,930 person-trials; 4,044 unique individuals), 3,321 person-trials received a third dose at time zero and 15,609 did not. At 6 months, weighted long COVID incidence was 0.9% (95% CI, 0.5%, 1.3%) with a third dose vs. 1.0% (0.8%, 1.1%) without (risk difference (RD), -0.1%; 95% CI, -0.5%, 0.4%; risk ratio (RR), 0.93; 95% CI, 0.54, 1.44). At 12 months, incidence was 4.9% (4.1%, 5.9%) with a third dose vs. 4.5% (4.1%, 4.8%) without (RD, 0.4%; 95% CI, -0.5%, 1.4%; RR, 1.09; 95% CI, 0.90, 1.33).<br><br>CONCLUSION: In this community-based target-trial emulation, receiving a third COVID-19 vaccine dose did not meaningfully reduce 6- or 12-month long COVID incidence compared with completing only a primary series.},
}
@article {pmid41282682,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Natural History of Self-reported Symptoms Following SARS-CoV-2 Infection: A Target Trial Emulation in a Prospective Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282682},
support = {UH3 AI133675/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: The natural history of symptoms after SARS-CoV-2 infection remains uncertain because many studies are non-representative, ignore background symptom prevalence, lack longitudinal tracking, and omit appropriate controls. Using a prospective, community-based cohort with repeated symptom measures, we estimated post-infection risks of long COVID symptoms versus contemporaneous uninfected controls.<br><br>METHODS: We analyzed the CHASING COVID Cohort, a U.S. longitudinal study with surveys and serology (March 2020-December 2023). Infection status (January 2021-December 2022) was determined from self-reported PCR/antigen results, serology, or CSTE probable criteria. We emulated 24 monthly target trials comparing individuals newly infected at time zero with those remaining uninfected. Outcomes were new-onset long-COVID symptoms not reported pre-infection, assessed overall and within three clusters (neurological, autonomic, exercise intolerance) at 4-8 and 9-12 months post-infection. Inverse probability of treatment and censoring weights adjusted for confounding and informative loss to follow-up.<br><br>RESULTS: The analysis included 1,055 infected and 52,310 uninfected person-trials. At 4-8 months, the adjusted risk of any long-COVID symptom was 22.6% (95% CI, 20.5-24.8) among infected versus 11.3% (11.1-11.5) among uninfected (adjusted risk difference [aRD], 11.3% [9.2-13.5]; adjusted risk ratio [aRR], 2.01 [1.81-2.20]). At 9-12 months, risks were 19.2% (17.0-21.3) vs 12.4% (12.2-12.7) (aRD, 6.7% [4.6-8.9]; aRR, 1.54 [1.37-1.72]). Across all three clusters, infected participants had consistently higher risks at both intervals.<br><br>CONCLUSIONS: SARS-CoV-2 infection was associated with elevated risk of new-onset long-COVID symptoms persisting up to 12 months. Using a national community-based cohort, contemporaneous uninfected controls, and target-trial emulation clarifies the burden attributable to infection and supports ongoing surveillance and targeted prevention and care.},
}
@article {pmid41282213,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and Alarab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: Lung Pathophysiology and its Relationship with Cognitive Dysfunction.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41282213},
issn = {2693-5015},
support = {R01 HL126771/HL/NHLBI NIH HHS/United States ; R01 HL169765/HL/NHLBI NIH HHS/United States ; S10 OD026960/OD/NIH HHS/United States ; UM1 TR004403/TR/NCATS NIH HHS/United States ; },
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and 129 Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age=54±11 yrs.; 10 females) that were 32±5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower 129 Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}
@article {pmid41282195,
year = {2025},
author = {Dominguez, JC and Fowler, KC and Koralnik, IJ and Liow, K and Ampil, E and Zhi, Q and Laxamana, L and Berroya, R and Noris, CJ and Meropol, SB and Troxel, AB},
title = {Analysis of the National Institutes of Health COVID-19 Neuro Databank by geographic region and income status.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41282195},
issn = {2693-5015},
support = {U24 NS113844/NS/NINDS NIH HHS/United States ; },
abstract = {BACKGROUND: While COVID-19 is more commonly known to present and persist in terms of respiratory symptoms, evidence for neurologic manifestations is limited.<br><br>OBJECTIVES: This study aims to provide an epidemiological overview of neurologic manifestations of COVID-19. It compares the demographic and clinical profiles of patients based on geographic location and country income classification. Moreover, it describes the neurologic manifestations of Long COVID.<br><br>METHODS: This was a cross-sectional analysis of a multi-country cohort of patients with COVID-19-associated neurologic symptoms enrolled in the COVID-19 Neuro Databank from January 2020 to February 2025. Demographic, clinical and health system-related factors were described. Comparisons among geographic regions and income classifications were performed via analysis of variance and chi-square tests or Fisher's exact tests.<br><br>RESULTS: Majority of the 3,901 patients were from the United States (U.S.) and from high-income countries. The mean age was 57.27&#xb1;18 years and 54% were males. Neurologic comorbidities were highest in the U.S. whereas non-neurologic comorbidities. Asia had the greatest frequency of severe COVID and mortality. Vaccination and use of COVID-19 medication was lowest in Africa. There were significant associations between COVID-19 vaccination and use of COVID-19 medications with income level. The five leading COVID-19-associated neurologic conditions were neurocognitive disorders, fatigue, headache, anosmia, and ageusia. A subset of Long COVID was identified as thought disorders, fatigue, mood disorders, stroke, headache, and neurocognitive disorders.<br><br>CONCLUSIONS: This study provides insight into the varying profile and burdens of COVID-19 associated neurologic conditions and the health inequities during the pandemic among geographic and income groups.},
}
@article {pmid41280901,
year = {2025},
author = {Fricke, F and Mai, F and Wossidlo, C and Steinbeck, F and Bergmann-Ewert, W and Kordt, M and Kraft, K and Müller, B and Reisinger, EC and Müller-Hilke, B},
title = {Transcriptome analysis of classical blood cells reveals downregulation of pro-inflammatory genes in the classical monocytes of long COVID patients.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1710783},
pmid = {41280901},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/genetics/blood ; *Monocytes/immunology/metabolism ; Male ; Female ; Gene Expression Profiling ; *SARS-CoV-2/immunology ; Middle Aged ; Down-Regulation ; Adult ; *Transcriptome ; Inflammation/genetics/immunology ; Single-Cell Analysis ; Cytokines/blood ; Aged ; Leukocytes, Mononuclear/immunology ; },
abstract = {INTRODUCTION: Despite extensive research, the pathogenesis and predispositions underlying long COVID (long-term coronavirus disease 2019) remain poorly understood.<br><br>METHODS: To address this, we analyzed the immunological landscapes of 44 patients with long COVID and 44 matched convalescents using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and validated the findings with plasma cytokine measurements via Luminex technology.<br><br>RESULTS: While the immune cell compositions showed minimal quantitative differences only among natural killer (NK) cells, the transcriptome analyses identified distinct gene expression patterns, particularly in classical monocytes: patients with long COVID exhibited downregulation of the inflammation-associated genes, including IL1B and CXCL2. Imputation of the transcription factor activity hinted at a reduced inflammasome activity (via SNAI1) and an impaired monocyte differentiation (via ATF2) in long COVID. The RNA velocity data supported the presence of immature classical monocytes in these patients.<br><br>DISCUSSION: These findings show that monocytes might be dysregulated and/or exhausted in patients with long COVID.},
}
@article {pmid41280592,
year = {2025},
author = {},
title = {Erratum: An audit of 12 cases of long COVID following the Lightning Process intervention examining benefits and harms.},
journal = {Journal of family medicine and primary care},
volume = {14},
number = {10},
pages = {4407},
pmid = {41280592},
issn = {2249-4863},
abstract = {[This corrects the article on p. 796 in vol. 14, PMID: 40115575.].},
}
@article {pmid41279626,
year = {2025},
author = {Liu, JA and Chaulagain, S and Creisher, PS and Zhong, W and Zhang, T and Taddese, M and Shi, K and Park, HS and Hcnir, H and Arnold, AP and Baric, R and Barahona, NB and Engler-Chiurazzi, E and Zwezdaryk, KJ and Thio, CL and Balagopal, A and Harkema, JR and Thompson, EA and Pekosz, A and Cox, AL and Klein, SL},
title = {Mechanisms of sex differences in acute and long COVID sequelae in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279626},
issn = {2692-8205},
support = {75N93021C00045/AI/NIAID NIH HHS/United States ; R01 AG082899/AG/NIA NIH HHS/United States ; R01 HD100298/HD/NICHD NIH HHS/United States ; U19 AI159822/AI/NIAID NIH HHS/United States ; },
abstract = {While males are more likely to suffer severe outcomes during acute COVID-19, a greater proportion of females develop post-acute sequalae of COVID-19 (PASC) despite similar rates of infection. To identify mechanisms of PASC, mice were infected with SARS-CoV-2 and viral, inflammatory, and behavioral outcomes were evaluated through 84 days post infection. Sex differences were not observed in virus replication or persistence of viral RNA in pulmonary or extrapulmonary tissues in acute or PASC phases. Following recovery from infection, female mice exhibited persistent neurocognitive and behavioral impairments, along with greater frequencies of inflammatory myeloid subsets, neuroinflammation, and dysregulated T cell subsets, including Tregs. Sex differences in inflammation and cognitive phenotypes during PASC were mediated by the presence of two X chromosomes. XX animals independent of chromosome Y presented with neuroinflammation and PASC along with infection-induced upregulation of the X-linked genes Xist and Tlr7 that regulate inflammation and chronic disease outcomes.},
}
@article {pmid41278460,
year = {2025},
author = {Zheng, T and Gao, R and Liu, Y and Wang, Y and Wu, C and Guo, L and Chen, L and Wang, X and Xiao, Y and Zhong, J and Zhang, R and Wang, Y and Ren, X and Cao, B and Ren, L and Wang, J},
title = {T cell-driven sustained inflammation and immune dysregulation mimicking immunosenescence for up to three years post-COVID-19.},
journal = {Immunity &amp; inflammation},
volume = {1},
number = {1},
pages = {11},
pmid = {41278460},
issn = {3059-4774},
abstract = {UNLABELLED: Long COVID has emerged as a major global health concern, yet the long-term trajectory of immune recovery and its contribution to persistent symptoms remain to be elucidated. Here, we conducted a three-year longitudinal follow-up of the 47 COVID-19 patients and applied single-cell RNA sequencing (scRNA-seq) and multiplex cytokine profiling to comprehensively characterize the peripheral immune landscape during convalescence. We observed persistent immune dysregulation up to three years post-infection, characterized by chronic inflammation and impaired restoration of naïve CD4[+] T cells, naïve CD8[+] T cells, and SLC4A10[+] MAIT cells-features reminiscent of immunosenescence. Notably, Th17 cells, rather than monocytes, emerged as key drivers of chronic inflammation beyond one year. We identified two distinct Th17 subsets: RORC[+] Th17 cells and LTB[+] Th17 cells. While RORC[+] Th17 cells were negatively correlated with inflammatory cytokine levels, LTB[+] Th17 cells showed proinflammatory features and were positively associated with long COVID symptoms. Sustained elevation of S100A8 and IL-16 in follow-up patients may contribute to the persistent presence of LTB[+] Th17 cells. Together, our study provides an in-depth longitudinal map of immune remodeling in COVID-19 convalescents, revealing key cellular and molecular drivers of sustained inflammation up to three years post-infection.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44466-025-00012-2.},
}
@article {pmid41277895,
year = {2025},
author = {Cabello Fernandez, C and Didone, V and Lesoinne, A and Slama, H and Fery, P and Rousseau, AF and Moutschen, M and , and Collette, F and Willems, S},
title = {Cognitive and affective psychoeducation for Long COVID: a randomized controlled trial.},
journal = {Brain communications},
volume = {7},
number = {6},
pages = {fcaf447},
pmid = {41277895},
issn = {2632-1297},
abstract = {Long COVID is a complex condition characterized by persistent symptoms, including cognitive difficulties and fatigue, which significantly impact daily functioning. Although various intervention strategies inspired by approaches used in the rehabilitation of other neurological conditions have been developed to address these issues, evidence of their efficacy in Long COVID populations remains limited. This study aimed to compare the effectiveness for cognitive complaints of two psychoeducational interventions-one focused on cognitive difficulties and the other on affective symptoms in Long COVID patients with cognitive problems. COVCOG (Long COVID: treatment of cognitive difficulties) is a randomized controlled trial using a parallel two-group design. Long COVID patients underwent neuropsychological assessments at pre-, 2- and 8-month post-intervention. The intervention comprised four 90-min sessions of either a cognitive-focused or an affective-focused psychoeducational programme. The effects were measured on cognitive complaints (primary outcome), cognitive performance, fatigue, sleep difficulties, quality of life, psychological distress, and impact on work and daily activities (secondary outcomes). Linear mixed models (LMMs) were used. One hundred and thirty Long COVID patients were randomized. One hundred and twenty-two (mean age: 47 ± 10; 69.7% female) were included (63 in the cognitive group and 59 in the affective group). The low dropout rate (12% at 2 months and 9% at 8 months post-intervention) and the patients' substantial active engagement-92% attended all intervention sessions-assured the feasibility of both interventions. LMM analysis revealed a statistically significant improvement with time in subjective cognitive complaints, objective cognitive performance (attention, working memory and long-term memory), quality of life, fatigue, sleep, some psychological distress subscales and work impairment (all Ps < 0.03, with small to moderate effect sizes), but no group-by-time interaction, suggesting that trajectories did not differ between arms. However, some improvements are specific to one intervention or the other. Designed specifically for this population, both psychoeducative interventions provide insights into improving the management of Long COVID patients with cognitive problems. Longer treatment may be needed for more meaningful improvements. Clinicaltrials.gov: NCT05167266.},
}
@article {pmid41277355,
year = {2025},
author = {Foscolou, A and Pratti, T and Detopoulou, P and Argyri, K and Nikolaou, G and Kouskouti, A and Malikourti, A and Petrogianni, M and Shurdha, E and Psaroudaki, E and Panoutsopoulos, GI and Vamvakas, S and Gioxari, A},
title = {Dietary n-3 Polyunsaturated Fatty Acids From Fish Are Associated With Better Healthy Aging Indicators: Results of the DIAPELH Study.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {38},
number = {6},
pages = {e70169},
pmid = {41277355},
issn = {1365-277X},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Fatty Acids, Omega-3/administration &amp; dosage ; Aged ; Male ; Female ; Cross-Sectional Studies ; *Healthy Aging/physiology ; Greece/epidemiology ; Middle Aged ; *Fishes ; Animals ; Diet, Mediterranean/statistics &amp; numerical data ; *Seafood ; COVID-19/epidemiology ; *Diet ; Cognition ; Aged, 80 and over ; Depression/prevention &amp; control ; SARS-CoV-2 ; Aging ; },
abstract = {INTRODUCTION: Promoting healthy aging is a public health goal, especially in regions with a high proportion of older adults, such as Greece. This cross-sectional study investigated the association of fish n-3 PUFA intake with indicators of healthy aging among older Greek Peloponnesian adults.<br><br>METHODS: In total, 449 individuals >&#x2009;60 years of age were enroled. Sociodemographic, anthropometrical, medical, mobility, balance, lifestyle, dietary, cognitive and mental characteristics were assessed through validated questionnaires and procedures.<br><br>RESULTS: Analyses revealed that n-3 PUFA intake was associated with fewer depression symptoms (p&#x2009;<&#x2009;0.001), higher cognition levels (p&#x2009;=&#x2009;0.012) and levels of healthy aging (p&#x2009;<&#x2009;0.001), derived from Successful Aging Index (SAI). In parallel, n-3 PUFA intake was associated with higher adherence to the Mediterranean diet (p&#x2009;<&#x2009;0.001). Additionally, n-3 PUFA intake was inversely correlated with the presence of long COVID-19 symptomatology (p&#x2009;=&#x2009;0.036). No association of n-3 PUFA intake with mobility or physical performance and balance (all ps>&#x2009;0.05) was detected.<br><br>CONCLUSION: The results underscore the significance of nutrition in older adults, highlighting the possible protective impact of n-3 PUFAs on maintaining functionality. Future prospective studies may validate these associations and contribute to the development of targeted nutritional strategies for older adults.},
}
@article {pmid41277094,
year = {2025},
author = {Mustonen, T and Kytölä, P and Lantto, H and Lager, E and Vangelova-Korpinen, V and Virrantaus, H and Sulg, A and Stålnacke, S and Posharina, T and Luukkonen, R and Uusitalo, A and Piirilä, P and Kanerva, M},
title = {Characterization of sympathicotonia in post-covid condition (long covid) and healthy controls using long-term electrodermal activity (EDA) follow-up.},
journal = {Clinical physiology and functional imaging},
volume = {45},
number = {6},
pages = {e70037},
pmid = {41277094},
issn = {1475-097X},
support = {101057553//European Union's Horizon Europe research and innovation/ ; Y780022061//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; Y780024073//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; Y780023041//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/complications/physiopathology/diagnosis ; Middle Aged ; *Galvanic Skin Response ; Adult ; *Sympathetic Nervous System/physiopathology ; Case-Control Studies ; Time Factors ; Aged ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; },
abstract = {PURPOSE: After SARS-CoV-2 infection, some patients develop post-COVID condition (PCC), often associated with sympathicotonia. This study aimed to characterize sympathicotonia in PCC patients using a novel long-term electrodermal activity (EDA) analysis via a smart ring and evaluate its clinical applicability.<br><br>METHODS: Seventeen PCC patients were recruited from a Long Covid outpatient clinic, and 18 healthy controls volunteered. PCC patients were divided based on self-reported symptoms into those with or without sympathicotonia. A 14-day EDA monitoring was conducted. Sympathetic nervous system (SNS) activity was expressed as a double normalized index of electrodermal activity (DNE), with higher levels indicating higher SNS activity. Orthostatic tests were performed to identify orthostatic sympathicotonia. DNE levels, representing EDA, were compared to self-reported and orthostatic sympathicotonia.<br><br>RESULTS: DNE levels did not differ between PCC patients with (N&#x2009;=&#x2009;12) or without (N&#x2009;=&#x2009;5) self-reported sympathicotonia or compared with nonsympathetic controls. When dividing all participants by orthostatic test results, DNE levels were lower during day (08:00-14:00; p&#x2009;<&#x2009;0.05) but higher during late night (00:00-02:00; p&#x2009;<&#x2009;0.05) in those with orthostatic sympathicotonia (N&#x2009;=&#x2009;21) compared to those without (N&#x2009;=&#x2009;14), with the 24-h comparison significant (p&#x2009;=&#x2009;0.022). Among PCC patients, DNE levels were higher in orthostatic nonsympathicotonic (N&#x2009;=&#x2009;7) than orthostatic sympathicotonic (N&#x2009;=&#x2009;10) during morning (09:00-12:00; p&#x2009;<&#x2009;0.05), with the 24-h comparison significant (p&#x2009;=&#x2009;0.044).<br><br>CONCLUSION: Self-reported symptoms did not distinguish sympathicotonia. However, individuals with orthostatic test-identified sympathicotonia had heightened EDA, indicating increased sympathetic activity, particularly during late night. PCC was not identifiable by EDA. Long-term EDA monitoring may provide an objective tool for detecting sympathicotonia independently of self-reported symptoms.},
}
@article {pmid41274384,
year = {2026},
author = {Schmitz, B and Garbsch, R and Schäfer, H and Bär, C and Chatterjee, S and Riemekasten, G and Schulze-Forster, K and Heidecke, H and Schultheiß, C and Binder, M and Mooren, FC},
title = {Autonomic dysfunction and vasoregulation in long COVID-19 are linked to anti-GPCR autoantibodies.},
journal = {The Journal of allergy and clinical immunology},
volume = {157},
number = {3},
pages = {722-738.e7},
doi = {10.1016/j.jaci.2025.10.034},
pmid = {41274384},
issn = {1097-6825},
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2-triggered autoantibodies (AABs) targeting G protein-coupled receptors have been suggested to contribute to the post-acute sequelae of coronavirus disease 2019 (or post-COVID-19 syndrome [PCS]).<br><br>OBJECTIVE: We sought to characterize AABs involved in autonomic dysfunction such as rhythm control and vasoregulation in patients with PCS and profile the peripheral B- and T-cell receptor (BCR/TCR) architecture to identify immunogenetic imprints of autoimmunity.<br><br>METHODS: Anti-G protein-coupled receptor AABs were characterized in patients with PCS with known alteration in autonomic nervous system functions assessed by heart rate variability. Adaptive immune receptor repertoire sequencing was used to profile peripheral BCR and TCR architecture. Patients with COVID-19 with severe or moderate acute disease, after recovery, and prepandemic healthy individuals served as controls. Cardio- and vasoactive effects of AABs were analyzed using 24-hour and exercise test blood pressure measurements. The direct effect of AABs on electromechanical coupling was tested in human-induced pluripotent stem cell cardiomyocytes.<br><br>RESULTS: AABs including autoantibody against angiotensin II receptor type 1/2, autoantibody against adrenoceptor beta 1/2, autoantibody against muscarinic acetylcholine receptor M1/M3, and autoantibody against C-X-C motif chemokine receptor 3 (CXCR3ab) were associated with heart rate variability alterations. Analysis of the broad BCR repertoire metrics revealed high similarity between patients with PCS and healthy controls for clonality and diversity measures. The level of somatic hypermutation as proxy for antigen experience was equal to that of healthy controls. Elevated CXCR3ab levels were linked to higher 24-hour mean arterial pressure, whereas patients with elevated autoantibody against muscarinic acetylcholine receptor M1 and CXCR3ab levels showed higher blood pressure during stress tests. AABs had no effect on beat frequency and amplitude of cardiomyocyte contraction in vitro.<br><br>CONCLUSIONS: These findings suggest that AABs play a modulatory role in sympathetic nervous system-mediated regulation of cardiac rhythm and vascular function in PCS. AAB levels did not correlate with BCR and TCR repertoire metrics or T-cell receptor beta variable gene usage.},
}
@article {pmid41272653,
year = {2025},
author = {Liu, B and Zhu, X and Ying, Y and Li, L and Zhou, H and Xu, Z and Wang, F and Jiang, L},
title = {Impact of COVID-19 lived experiences on future influenza pandemic worry: a cross-sectional survey in China.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {4405},
pmid = {41272653},
issn = {1471-2458},
support = {LGF22G030018//Zhejiang Province Public Welfare Technology Application Research Project/ ; 2023S027//Key Project of Ningbo Public Welfare Research Plan/ ; },
abstract = {BACKGROUND: Against the backdrop of repeated warnings regarding the inevitability of future influenza pandemics and the critical importance of public preparedness, the aim of this study was to explore public worry about a future influenza pandemic and its influencing factors in the post-coronavirus disease 2019 (COVID−19) era, particularly focusing on the role of lived experiences during the COVID−19 pandemic.<br><br>METHODS: An online cross-sectional study was conducted between October and December 2024. Overall, 1254 valid samples were finally included. Descriptive analysis and hierarchical logistic regression were performed to examine the associations between potential influencing factors and public worry about a future influenza pandemic.<br><br>RESULTS: Approximately 48.49% of the participants reported being worried about a future influenza pandemic. The final model of hierarchical logistic regression revealed that sex, educational level, having one or more children in the family, lived experiences (repeated infections, long-COVID, medical resource shortages), and risk perceptions (perceived likelihood and severity) were associated with worry about a future influenza pandemic.<br><br>CONCLUSION: This study reveals that lived experiences during the COVID&#x2212;19 pandemic are associated with increased worry about a future influenza pandemic by the public. The factors identified can be used to guide the development of evidence-based risk communication and preparedness strategies to foster public participation. Crucial baseline data were also provided from a specific period to monitor changes in public perceptions of influenza pandemic threats over time.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25704-7.},
}
@article {pmid41272382,
year = {2026},
author = {Dornas, W and Reis, JP and Belilo, TE and Vaz, LG and Nasser, HH and de Souza Maia, ML and Figueiredo, A and Tcherniacovski, AG and Montenegro, LCC and Yang, X and C Santiago, H},
title = {Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis.},
journal = {Inflammopharmacology},
volume = {34},
number = {1},
pages = {1-16},
pmid = {41272382},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/immunology/blood/complications ; *Cytokines/blood/metabolism ; *Inflammation/immunology ; },
abstract = {Post-acute sequelae of Covid-19 (PASC) refer to persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. However, identifying biological mechanisms, potential therapeutic targets, and modifiable environmental risk factors remains necessary. Here, we analyzed cytokine levels in patients with PASC through a systematic literature search of the PubMed/MEDLINE, Web of Science, and Scopus databases, including articles published up to December 2024. A total of 33 studies (comprising 3294 patients) were included, addressing the long-term sequelae following acute Covid-19 infection. Levels of IL-6, IL-2, MCP-1/CCL2, TNF-α, IFN-γ, and IP-10/CXCL10 were higher in Covid-19 patients with PASC compared to those without PASC, suggesting an inflammatory basis for the persistence of symptoms. Conversely, little or no difference was observed for IL-1β, IL-7, IL-10, IL-4, IL-17A, IL-8, and IL-1α. To assess the duration of the sustained inflammatory response post-infection, cytokine measurements were categorized as < 6 months or ≥ 6 months after diagnosis. IL-6, MCP-1/CCL2, TNF-α, and IFN-γ remained elevated in both time windows, while IL-1β, IL-8, IP-10/CXCL10, IL-2, and IL-10 showed increased levels beyond 6 months post-Covid-19 diagnosis. Our findings indicate that persistent elevation of inflammatory cytokine is associated with PASC, contributing to a better understanding of the immune pathology underlying chronic dysfunction related to Covid-19.},
}
@article {pmid41271803,
year = {2025},
author = {Bansal, A},
title = {Economic burden of long COVID: macroeconomic, cost-of-illness and microeconomic impacts.},
journal = {NPJ primary care respiratory medicine},
volume = {35},
number = {1},
pages = {53},
pmid = {41271803},
issn = {2055-1010},
mesh = {Humans ; *COVID-19/economics/epidemiology ; *Cost of Illness ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health ; Unemployment ; },
abstract = {Long COVID, defined by symptoms persisting three months post-SARS-CoV-2 infection, presents a significant global health and economic challenge, with global prevalence estimated at 36% (ranging from 1-92%). This brief communication consolidates current knowledge on its economic impacts, including macroeconomic, cost-of-illness, and microeconomic impacts, which are estimated at an average annual burden of $1 trillion globally and $9000 per patient in the USA, with some individuals covering substantial out-of-pocket expenses. Annual lost earnings in the USA alone are estimated at approximately $170 billion. Long COVID was associated with increased unemployment, financial distress, and work impairment for up to three years post-infection. This paper highlights discrepancies in impact estimation methodologies and calls for standardised metrics especially in emerging economies. Key research gaps include the absence of comprehensive longitudinal studies on individual and aggregated economic burden, specific long COVID phenotypes and biomarkers, and cost-effectiveness evaluations of interventions.},
}
@article {pmid41271424,
year = {2025},
author = {Seboka, BT and Smith, J and Whitmore, K and Baranow, B and Howden, E and Kulkarni, J and Huynh, QL and H Marwick, T},
title = {Depression as a moderator and mediator of functional status in patients with Long COVID: a cross-sectional and longitudinal observational study from the PERCEIVE cohort in Australia.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e099776},
pmid = {41271424},
issn = {2044-6055},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *COVID-19/psychology/complications/epidemiology/physiopathology ; Longitudinal Studies ; Middle Aged ; *Depression/epidemiology ; Adult ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; Tasmania/epidemiology ; Victoria/epidemiology ; },
abstract = {BACKGROUND: In patients with post-acute sequelae of COVID-19 (PASC), depression has been associated with symptom severity, the duration since infection and ongoing functional impairment. However, the interconnections between these factors remain inadequately understood.<br><br>OBJECTIVES: This study aimed to explore the roles of depressive symptoms in moderating and mediating the relationships between post-COVID-19 conditions and functional capacity.<br><br>METHODS: The PERCEIVE study recruited 1794 participants from Victoria and Tasmania through online advertisements based on possible PASC for a cross-sectional study. Of these, 461 participated in the longitudinal study. Post-COVID-19 duration and symptoms were recorded, and depressive symptoms and functional capacity were self-reported using the 9-item Patient Health Questionnaire and the Duke Activity Status Index (DASI), respectively. The association of depression with functional capacity was explored using ordinary least squares (OLS) regression, with companion OLS models, Sobel-Goodman tests and 1000 bootstrap iterations to assess mediation. Longitudinal data were analysed to assess changes in functional capacity and depressive symptoms over time, with mediation analysis using mixed models to explore depression as a mediator.<br><br>RESULTS: Participants had a mean DASI score of 35 (SD 21). Fatigue (18%), shortness of breath (11%) and chest pain (6%) were common symptoms, with severe depression linked to fatigue (93%) and shortness of breath (66%). The severity of post-COVID-19 symptoms was associated with severe depression (&#x3b2;=6.31, 95% CI 5.42 to 7.21) and reduced functional capacity (&#x3b2;=-6.40, 95% CI -9.20 to -3.61), with depression mediating 36% of the association between post-COVID-19 symptom severity and functional capacity. PASC was associated with higher depression scores (&#x3b2;=2.06, 95% CI 1.15 to 2.97) and lower functional capacity (&#x3b2;=-3.99, 95% CI -6.21 to -1.77), with depression mediating 51% of the association between PASC and reduced functional capacity. The longitudinal analysis suggested that depression is associated with the relationship between PASC and changes in functional capacity over time (unstandardised estimate=-5.16, p<0.001).<br><br>CONCLUSION: Depression plays a key role in exacerbating post-COVID-19 functional impairment. This observation underscores the need for targeted physical and mental health interventions to enhance long-term recovery for those with severe conditions.},
}
@article {pmid41269680,
year = {2025},
author = {Pant, S},
title = {Resistance Training Improves Long COVID Outcomes.},
journal = {JAMA},
volume = {334},
number = {24},
pages = {2156},
doi = {10.1001/jama.2025.19746},
pmid = {41269680},
issn = {1538-3598},
}
@article {pmid41269415,
year = {2025},
author = {de Almeida Gomes, I and Braga-Neto, P and Matos, TL and da Silva, EL and de Oliveira, LLB and Lima, LB and Tavares-Júnior, JWL and Moura, AEF and de Andrade, MH and de Maria Frota Vasconcelos, T and Oriá, RB and Oliveira, DN and Sobreira-Neto, MA and Souza, PFN and de Moraes, MEA and Mesquita, FP and Montenegro, RC},
title = {Associations Between APOE Polymorphisms, Neurological Symptoms, and Cognitive Assessments in Long COVID Patients: An Analysis of SNPs rs7412 and rs429358.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {113},
pmid = {41269415},
issn = {1559-1182},
mesh = {Humans ; *Polymorphism, Single Nucleotide/genetics ; Male ; Female ; *COVID-19/genetics/complications/psychology ; *Apolipoproteins E/genetics ; Middle Aged ; *Cognition/physiology ; Aged ; Genetic Predisposition to Disease ; Genetic Association Studies ; Alleles ; Genotype ; Adult ; },
abstract = {Long COVID has been associated with persistent neurological symptoms that impair cognitive function and quality of life, raising questions about the role of genetic factors in symptom severity and persistence. Apolipoprotein E (APOE) polymorphisms, known for their relevance in neurodegenerative diseases, may significantly influence neurological outcomes in long COVID patients. This study aimed to investigate the relationship between APOE polymorphisms, specifically single nucleotide polymorphisms (SNPs) rs7412 and rs429358, and neurological and cognitive symptoms in long-term COVID patients. APOE genotypes were identified through the analysis of SNPs rs7412 and rs429358. Cognitive and behavioral assessments were conducted using the Mini-Mental State Examination (MMSE), the Pfeffer Functional Activities Questionnaire, the Beck Inventory for mood assessment and the Epworth Sleepiness Scale (ESS). Statistical analyses included Mann-Whitney U test, chi-square or Fisher's exact test, and odds ratio calculation, using R Studio and GraphPad Prism. The results indicated that the ε2ε3 genotype was associated with lower scores on the BECK, suggesting fewer depressive symptoms, while the ε3ε3 genotype was linked to an increase in depressive symptoms. Furthermore, analyses of APOE alleles showed an opposite pattern concerning daytime sleepiness: carriers of the ε2 allele exhibited greater daytime sleepiness, whereas ε3 allele carriers reported less sleepiness, as measured by the ESS. The analysis of the rs7412 SNP revealed significant impacts on both BECK and ESS scores. These findings suggest that APOE polymorphisms, particularly the ε2 and ε3 alleles, play a crucial role in modulating neurological and cognitive symptoms associated with long COVID. The results highlight the potential of genetic screening to identify patients at higher risk of persistent cognitive and emotional alterations, emphasizing the importance of personalized management strategies and the need for further research in diverse populations.},
}
@article {pmid41268552,
year = {2025},
author = {Rosa, BA and Bigham, M and Darling, TL and Arun, A and Singh, KS and Martin, J and Boon, ACM and Mitreva, M},
title = {Hookworm infection modulates lung and intestinal transcriptomic responses to SARS-CoV-2 in Syrian hamsters.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1701728},
pmid = {41268552},
issn = {1664-3224},
support = {UL1 TR002345/TR/NCATS NIH HHS/United States ; },
mesh = {Animals ; *COVID-19/immunology/genetics/virology ; *SARS-CoV-2/immunology/physiology ; *Transcriptome ; *Lung/immunology/virology/metabolism ; Mesocricetus ; *Intestines/immunology/virology ; Cricetinae ; Disease Models, Animal ; Coinfection/immunology ; *Ancylostoma/immunology ; *Hookworm Infections/immunology ; Humans ; Gene Expression Profiling ; Male ; },
abstract = {BACKGROUND: Helminth infections are widespread in resource-limited settings, and modulate host immune responses, with potential implications for viral coinfections. Intestinal helminths can alter susceptibility to respiratory viruses, but the mechanisms influencing SARS-CoV-2 infection outcomes remain poorly understood.<br><br>METHODS: Using the Syrian hamster model, we investigated the impact of prior infection with the human hookworm Ancylostoma ceylanicum on host responses to SARS-CoV-2. Tissue-specific transcriptional responses were compared among four groups: naive, hookworm-only, SARS-CoV-2-only, and coinfected with both pathogens, 3 and 6 days post-viral infection. Viral titers and weight loss were assessed, and RNA-seq transcriptome profiles from lung and intestinal tissues were interrogated to identify differentially expressed genes and cellular pathways.<br><br>RESULTS: Prior hookworm infection did not significantly alter viral titers or weight loss compared to SARS-CoV-2 infection alone, but distinct transcriptional signatures compared were identified compared to either single infection. Coinfection uniquely differentially regulated hematopoiesis and B cell-associated genes (e.g., ATF5, IGHM, JCHAIN) in the lungs, and immune and stress response pathways and inflammation-associated genes (e.g. FOLR2, PLA2GF, FABP3) in the intestine. Genes and pathways differentially regulated by SARS-CoV-2 alone, but with attenuated transcriptional responses in the lungs of coinfected hamsters were observed, including the loss of upregulation of toll-like receptor signaling and previously proposed host biomarkers for COVID-19 severity (CHI3L1, HMOX1), Long COVID (FCG4/FCGR3A and FST) and mortality (FST). In the intestine, hookworm-associated suppression of type I interferon-related genes (TAP1, IRF7) was reversed with SARS-CoV-2 coinfection, highlighting pathogen-specific modulation of innate antiviral signaling. Genes and pathways consistently differentially regulated by with SARS-CoV-2 were consistent with expectations, and many hemoglobin pathways were differentially regulated with hookworm in the intestine. CIBERSORT analysis was estimated relative leukocyte abundances in each sample cohort.<br><br>CONCLUSION: Our findings demonstrate that A. ceylanicum infection reshapes host transcriptional responses to SARS-CoV-2 in a tissue-specific manner, enhancing B cell immunity in the lung while driving intestinal inflammation. Hookworm-induced immune modulation attenuated key SARS-CoV-2-responsive genes and pathways, suggesting potential mechanisms for reduced disease severity observed in helminth-endemic regions. These findings establish a molecular framework to better understand helminth, SARS-CoV-2 and host immune interactions, with relevance for other respiratory viral infections.},
}
@article {pmid41268373,
year = {2025},
author = {Calleja-Conde, J and Echeverry-Alzate, V and Sánchez-Diez, S and Giné, E and Bühler, KM},
title = {Severe alcohol use and COVID-19: implications for physical and mental health.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1640207},
pmid = {41268373},
issn = {1664-0640},
abstract = {The COVID-19 pandemic has revealed and intensified the vulnerability of individuals with pre-existing medical and behavioral conditions, notably those related to substance use. Among these, chronic alcohol consumption represents a clinically significant, yet often under-addressed, vulnerability factor that may exacerbate both the acute severity and long-term consequences of SARS-CoV-2 infection. This narrative review examines the biological and clinical intersections between alcohol use and COVID-19, focusing on shared mechanisms of immune dysfunction, neuroinflammation, and disruption of the gut-brain axis. We synthesize current findings showing that both conditions compromise innate and adaptive immune responses, alter cytokine signaling, and weaken mucosal and blood-brain barriers. These changes contribute to cognitive and emotional dysregulation and may increase the risk of persistent neuropsychiatric symptoms, including those observed in Long COVID. In addition, we discuss how chronic alcohol use may alter host susceptibility to infection and affect the immune response to vaccination, with implications for treatment outcomes and recovery. Our findings highlight the need to integrate alcohol use disorder into COVID-19 risk assessments, clinical management, and long-term mental health care planning. A multidisciplinary approach is essential to address the overlapping biological pathways that link alcohol-related vulnerability to COVID-19 outcomes.},
}
@article {pmid41267377,
year = {2025},
author = {},
title = {Correction to "The effect of uninterrupted and interrupted sitting on vascular function in adults with long COVID".},
journal = {Physiological reports},
volume = {13},
number = {22},
pages = {e70658},
doi = {10.14814/phy2.70658},
pmid = {41267377},
issn = {2051-817X},
}
@article {pmid41266487,
year = {2025},
author = {Richards-Belle, A and Shafran, R and Rojas, NK and Stephenson, T and Carr, E and Chalder, T and Dalrymple, E and McOwat, K and Simmons, R and Pinto Pereira, SM and , },
title = {Fatigue in children and young people up to 24 months after infection with SARS-CoV-2.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {41105},
pmid = {41266487},
issn = {2045-2322},
support = {COV-LT-0022//National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI)/ ; MR/Y009398/1//UK Medical Research Council/ ; },
mesh = {Humans ; Child ; *COVID-19/complications/virology/epidemiology ; Female ; Male ; *Fatigue/etiology/epidemiology/diagnosis ; Adolescent ; Longitudinal Studies ; SARS-CoV-2/isolation &amp; purification ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; },
abstract = {Persistent fatigue is common following acute SARS-CoV-2 infection. Little is known about post-infection fatigue trajectories in children and young people (CYP). This paper reports on a longitudinal analysis of the Children and Young People with Long COVID study. SARS-CoV-2-positive participants, aged 11-to-17-years at enrolment, responding to follow-ups at 3-, 6-, 12-, and 24-months post-infection were included. Fatigue was assessed via the Chalder Fatigue Scale (CFQ; score range: 0-11, with ≥4 indicating clinical case-ness) and by a single-item (no, mild, severe fatigue). Fatigue was described cross-sectionally and examined longitudinally using linear mixed-effects models. Among 943 SARS-CoV-2-positive participants, 581 (61.6%) met CFQ case-ness at least once during follow-up. A higher proportion of ever-cases (vs. never-cases) were female (77.1% vs. 54.4%), older (mean age 15.0 vs. 13.9 years), and met Post-COVID Condition criteria 3-months post-infection (35.6% vs. 7.2%). The proportion of CFQ cases increased from 35.0% at 3-months to 40.2% at 24-months post-infection; 15.9% meet case-ness at all follow-ups. Single-item mild/severe responses showed sensitivity (≥0.728) and specificity (≥0.755) for CFQ case ascertainment. On average, CFQ scores increased by 0.448 points (95% CI, 0.252 to 0.645) over 24-months, but there were subgroup differences (e.g., fatigue increased faster in females than males and improved slightly in those meeting Post-COVID Condition criteria 3-months post-infection while worsening in those not meeting criteria). Persistent fatigue was prominent in CYP up to 24 months after infection. Subgroup differences in scores and trajectories highlight the need for targeted interventions. Single-item assessment is a practical tool for screening significant severe fatigue.},
}
@article {pmid41265281,
year = {2025},
author = {da Silva, EM and de Campos, CM and de Godoy, CG and de Oliveira, DB and Alonso, AC and da Silva, VC and Schmitt, ACB and Ochiai, GS and Viana, BOC and da Silva, JM and de Carvalho, CRF and de Carvalho, CRR and D'Andréa Greve, JM and Pompeu, JE},
title = {Predictors of persistent fatigue one year after severe COVID-19: A prospective cohort study on depression and lung function.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100846},
pmid = {41265281},
issn = {1980-5322},
mesh = {Humans ; Female ; *Fatigue/physiopathology/etiology/epidemiology ; Male ; *COVID-19/complications/physiopathology/psychology ; Middle Aged ; Prospective Studies ; *Depression/epidemiology/etiology/physiopathology ; Adult ; Anxiety ; Prevalence ; Aged ; Respiratory Function Tests ; Time Factors ; Severity of Illness Index ; Spirometry ; Adolescent ; Young Adult ; *Lung/physiopathology ; Risk Factors ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Fatigue is among the most enduring symptoms of long COVID. However, the relationship between persistent fatigue and factors such as physical performance, lung function, anxiety, and depression in severe cases of COVID-19 remains underexplored.<br><br>OBJECTIVES: To assess the prevalence of fatigue and its association with these factors in patients one year after severe COVID-19 hospital discharge.<br><br>METHODS: This cohort comprised participants aged 18-years and older diagnosed with COVID-19. Evaluations were conducted at one, four, six-, and twelve-months following hospital discharge. Clinical data were collected, which included assessments of fatigue - Functional Assessment of Chronic Illness Therapy Fatigue subscale, lung capacity &#x2012; Spirometry, physical performance - 1-minute Sit to Stand Test, psychological aspects - Hospital Anxiety and Depression Scale, and functional capacity - Barthel index.<br><br>RESULTS: Of the 162 participants, 50 % experienced fatigue one-month post-discharge and this prevalence gradually decreased to 36 % by the end of one-year period. The fatigue group had a median age of 58-years. It was predominantly composed of women, with a majority identifying as non-white and having a body mass index greater than 30 kg/m[2]. Physical performance assessments within the fatigue group showed no significant changes over time, whereas lung capacity demonstrated significant improvement only at the 12-month mark. Additionally, anxiety and depression levels were significantly higher in the fatigue group over time (p < 0.05).<br><br>CONCLUSIONS: Fatigue persisted in 36 % of participants one-year post-hospital discharge. The potential predictors of long-term fatigue were depressive symptoms and impaired lung function observed within the first month after hospital discharge. Therefore, the authors highlight the importance of screening and monitoring these aspects in order to enable early intervention in this population.},
}
@article {pmid41264615,
year = {2025},
author = {Uwakwe, CK and Rangan, ES and Kumar, S and Gutjahr, G and Miao, X and Brooks, AW and Maguire, P and Mishra, T and McGuire, L and Snyder, MP},
title = {Longitudinal wearable sensor data enhance precision of Long COVID detection.},
journal = {PLOS digital health},
volume = {4},
number = {11},
pages = {e0001093},
pmid = {41264615},
issn = {2767-3170},
support = {S10 OD023452/OD/NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; },
abstract = {Despite the millions of individuals struggling with persistent symptoms, Long COVID has remained difficult to diagnose due to limited objective biomarkers, often leading to underdiagnosis or even misdiagnosis. To bridge this gap, we investigated the potential of utilizing wearable sensor data to aid in the diagnosis of Long COVID. We analyzed longitudinal heart rate (HR) data from 126 individuals with acute SARS-CoV-2 infections to develop machine learning models capable of predicting Long COVID status using derived HR features, symptom features, or a combination of both feature sets. The HR features were derived across six analytical categories, including time-domain, Poincaré nonlinear, raw signal, Kullback-Leibler (KL) divergence, variational mode decomposition (VMD), and the Shannon energy envelope (SEE), enabling the capture of heart rate dynamics over various temporal scales and the quantification of day-to-day shifts in HR distributions. The symptom features used in the final models included chest pain, vomiting, excessive sweating, memory loss, brain fog, heart palpitations, and loss of smell. The combined HR- and symptom-feature model demonstrated robust predictive performance, achieving an area under the Receiver Operating Characteristic curve (ROC-AUC) of 95.1% and an area under the Precision-Recall curve (PR-AUC) of 85.9%. These values represent a significant improvement of approximately 5% in both the ROC-AUC and PR-AUC over the symptoms-only model. At the population level, this improvement in discrimination could lead to clinically meaningful reductions in misclassification and improved patient outcomes, achieved through a non-invasive diagnostic tool. These findings suggest that wearable HR data could be used to derive an objective biomarker for Long COVID, thereby enhancing diagnostic precision.},
}
@article {pmid41262872,
year = {2025},
author = {Lv, X and Ji, L and Cao, W and Xue, Y and Dai, H and Zhang, S},
title = {Revisiting lung cancer immunotherapy in the era of long COVID: mechanistic insights and therapeutic implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1657691},
pmid = {41262872},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/complications ; *Immunotherapy/methods ; *Lung Neoplasms/therapy/immunology ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; },
abstract = {In the post-COVID-19 era, understanding the long-term impact of Long COVID on the immune system is essential for deciphering its influence on lung cancer pathogenesis and immunotherapeutic efficacy. This review comprehensively examines how persistent COVID-19 sequelae-manifested as chronic inflammation, pulmonary fibrosis, cytokine dysregulation, and T-cell exhaustion can reshape the lung cancer microenvironment. In addition, the emerging roles of memory B cells and altered neutrophil function in promoting tumorigenesis are discussed. Importantly, we analyze recent clinical evidence suggesting that COVID-19 vaccination may enhance the efficacy of immune checkpoint inhibitors, potentially by modulating host immunity. By integrating mechanistic insights with clinical observations, this review aims to illuminate the challenges and opportunities at the intersection of Long COVID and lung cancer treatment, thereby fostering the development of personalized therapeutic strategies in the post-pandemic era.},
}
@article {pmid41262358,
year = {2025},
author = {Goertzen, SM and Lindholm, DA and Walter, RJ and Huprikar, NA and Ganesan, A and Richard, SA and Mende, K and Harrell, TE and Peterson, PG and Simons, M and Tribble, DR and Agan, BK and Burgess, TH and Pollett, SD and Morris, MJ},
title = {Clinical, Radiographic, and Physiological Correlates of Post-COVID-19 Dyspnea in Military Health System Beneficiaries: Results From the Chronic Impairment With Pulmonary Symptoms (ChIPS) Sub-study.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf633},
pmid = {41262358},
issn = {2328-8957},
abstract = {BACKGROUND: Dyspnea has been described in up to 10-30% of patients post-SARS-CoV-2 infection. The underlying pathology for these persistent symptoms remains poorly understood. This study aimed to characterize changes in cardiopulmonary anatomical structure and physiology that may explain ongoing dyspnea after COVID-19.<br><br>METHODS: Participants had a history of symptomatic COVID-19, were between 18 and 65 years of age, and without significant pre-existing cardiopulmonary disease. Each participant underwent prospective chest high resolution computed tomography (HRCT), transthoracic echocardiography (TTE), electrocardiogram (ECG), pulmonary function testing (PFT) with lung volumes and diffusing capacity for carbon monoxide (DLCO), impulse oscillometry (IOS), and a six-minute walk test (6MWT) with Borg dyspnea scoring.<br><br>RESULTS: Among 115 enrolled participants, 39 had persistent dyspnea. The mean forced expiratory volume at 1 s/forced vital capacity (FEV1/FVC) ratio was higher in those with persistent dyspnea, but within normal ranges for both groups. There were no other statistically significant differences in FEV1, FVC, and DLCO between the groups. Those with ongoing dyspnea had a decreased walk distance (difference of 50.4 m, P = .01). Resting and post-6MWT Borg scores were 0.9 and 1.3 higher in those with persistent dyspnea, respectively (P-values <.001). There were no significant differences in IOS, HRCT, TTE, or ECG findings between groups.<br><br>CONCLUSIONS: This study demonstrated a difference in 6MWT distance and Borg scores between those with and without persistent dyspnea. There were no clear PFT, cardiac test, or HRCT findings that explained these persistent symptoms. Overall, this study demonstrates both subjective and objective differences between those with ongoing dyspnea following COVID-19 that are not explained by standard investigations typically ordered in clinical care for chronic dyspnea. These findings underscore the importance of further research into the etiology of post-COVID-19 dyspnea, including other investigations which may detect more subtle alterations in pulmonary physiology.},
}
@article {pmid41260143,
year = {2025},
author = {El Hajjar, AH and Zalaquett, Z and Rosenzveig, A and Syed, AB and Al-Dalakta, A and Majeed, Z and Villalonga, M and Ikram, J and Ehsan, M and Motairek, I and Heine, M and Berglund, F and Wang, TKM and Klein, A},
title = {Investigating Pericarditis Diagnosis in a Tertiary Pericardial Center: A Descriptive Study.},
journal = {JACC. Advances},
volume = {4},
number = {12 Pt 2},
pages = {102335},
pmid = {41260143},
issn = {2772-963X},
abstract = {BACKGROUND: Pericarditis diagnosis can be challenging due to its nonspecific presentation, which may lead to frequent misdiagnosis.<br><br>OBJECTIVES: In this study, the authors aimed to report the rate of misdiagnosed pericarditis and describe the characteristics of these patients.<br><br>METHODS: Between September 2022 and September 2023, patients referred to the Pericardial Center with a diagnosis of pericarditis were enrolled in a prospective registry. Data were collected using a standardized history and physical examination template. Diagnosis was established according to the 2015 European Society of Cardiology guidelines. The prevalence of misdiagnosed pericarditis was calculated. Demographics, comorbidities, symptoms, laboratory results, and imaging were compared between the accurately diagnosed (group 1) and misdiagnosed pericarditis cohorts (group 2).<br><br>RESULTS: A total of 170 patients were included; the mean age was 49.1 years. Thirty-five percent of patients were misdiagnosed. Demographics were similar in both groups. Significant differences were found between group 1 and group 2) in coronary artery disease (17.3% vs 5.0%, P = 0.02), valvular disease (23.6% vs 8.3%, P = 0.01), and atrial fibrillation (24.5% vs 6.7%, P < 0.01). Significant late gadolinium enhancement on magnetic resonance imaging, raised inflammatory markers, electrocardiogram changes, and specific pericardial pain were more common in the accurately diagnosed group (P < 0.05). COVID-19 infection was significantly higher in the misdiagnosed group (16.7% vs 6.4%, P < 0.05), whereas cardiac surgery was significantly lower (3.3% vs 18.2%, P < 0.05).<br><br>CONCLUSIONS: Thirty-five percent of patients referred to the pericardial center are misdiagnosed with pericarditis. Inflammatory markers and late gadolinium enhancement on magnetic resonance imaging can help refine the diagnosis. COVID-19 infection is associated with higher rates of misdiagnosis.},
}
@article {pmid41259895,
year = {2025},
author = {Ben, &#xc2;J and Kisiangani, I and Kinya, I and Wynberg, E and de Jong, MD and Schultsz, C and Asiki, G and Vassall, A},
title = {Long-Term Changes in Health-Related Quality of Life and Economic Burden After a SARS-CoV-2 Infection: Analysis of the Long COVID Prospective Cohort Study in Nairobi.},
journal = {Value in health regional issues},
volume = {53},
number = {},
pages = {101545},
doi = {10.1016/j.vhri.2025.101545},
pmid = {41259895},
issn = {2212-1102},
abstract = {OBJECTIVES: To characterize long-term changes in health-related quality of life (HRQoL) and factors associated with catastrophic expenditures and catastrophic costs after a SARS-CoV-2 infection.<br><br>METHODS: Data from 291 participants of the Long COVID Prospective Cohort Study in Nairobi were analyzed. Participants were enrolled between 2022 and 2023 and followed up for 12 months. Possible factors and outcomes (HRQoL, catastrophic expenditures, and catastrophic costs) were measured every 3 months. Changes in outcomes over time were assessed using generalized estimating equations.<br><br>RESULTS: HRQoL was significantly reduced by 11.4% (95% CI -16.3% to -6.5%), 8.6% (95% CI -12.5% to -4.6%), 6.1% (95% CI -10.5% to -1.8%), and 4.1% (95% CI -7.9% to -0.3%) at 6, 9, 12, and 15 months after a positive polymerase chain reaction test, respectively, compared with the period before COVID-19. HRQoL was significantly reduced by 3.3% (95% CI -6.2% to -0.5%), and 10.9% (95% CI -16.5% to -5.3%), respectively, in participants with any COVID-19-related symptoms or fatigue. Older age (odds ratio [OR] 5.83, 95% CI 2.11 to 16.15), no COVID-19 vaccination (OR 5.83, 95% CI 2.11 to 16.15), any COVID-19-related symptoms (OR 2.22, 95% CI 1.15 to 4.28), and pay cut or reduced income due to COVID-19-related symptoms (OR 17.36, 95% CI 2.28 to 132.07) were associated with high odds of experiencing catastrophic expenditures. Severe/critical SARS-CoV-2 infection (OR 4.77, 95% CI 1.72 to 13.25) and fatigue (OR 2.27, 95% CI 1.03 to 4.96) significantly increased the odds of experiencing catastrophic costs, whereas better HRQoL (OR 0.12, 95% CI 0.02 to 0.57) and social support (OR 0.30, 95% CI 0.09 to 0.93) decreased the odds.<br><br>CONCLUSIONS: HRQoL remains reduced up to 15 months after a SARS-CoV-2 infection compared with pre-COVID-19 levels, with participants in better health and socioeconomic status less likely to experience catastrophic expenditures and catastrophic costs.},
}
@article {pmid41259457,
year = {2025},
author = {Hi, EMB and Bianchi, CCR and Gritte, RB and Klauss, PHA and Leal, NFSM and Oliveira, IS and Barros, MFCB and Soriano, FG and Curi, R and Machado, MCC},
title = {Detection of autoantibodies in severe COVID-19 patients two years after hospital discharge.},
journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas},
volume = {58},
number = {},
pages = {e14927},
pmid = {41259457},
issn = {1414-431X},
mesh = {Humans ; *COVID-19/immunology/blood ; Middle Aged ; Male ; Female ; Aged ; *Autoantibodies/blood ; Adult ; Aged, 80 and over ; SARS-CoV-2/immunology ; Young Adult ; Biomarkers/blood ; Brazil ; Patient Discharge ; Procalcitonin/blood ; Antibodies, Antinuclear/blood ; C-Reactive Protein/analysis ; Case-Control Studies ; Rheumatoid Factor/blood ; Severity of Illness Index ; },
abstract = {After SARS-CoV-2 infection, severe COVID-19 may develop with persistent sequelae, even after hospital discharge. This condition may result from tissue damage or immune alterations caused by the virus, including immune dysregulation, hyperinflammation, loss of immune tolerance, excessive neutrophil extracellular trap (NET) production, and antibody cross-reactivity (molecular mimicry), which can promote autoantibody development. This study evaluated autoantibody expression in patients with long COVID-19 and its potential relationship with symptoms. Conducted in Baixada Santista, São Paulo, Brazil, the study involved 55 participants aged 21-85 years who had tested positive for SARS-CoV-2. Blood samples were collected two years post-discharge, and serum was analyzed for inflammatory and autoimmune markers, including antinuclear antibody (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), procalcitonin (PCT), Venereal Disease Research Laboratory test (VDRL), and C-reactive protein (CRP). Results were compared to a control group of 21 individuals who never tested positive for COVID-19. Among severe COVID-19 patients, 26 reacted to ANA, 16 to VDRL, 2 had elevated RF, 12 had increased PCT, and 11 had high CRP, whereas the control group showed no reactive results. Anti-CCP values were not significant. Findings suggest that hyperinflammation may contribute to autoimmunity, particularly in cases of reactive ANA levels, linking COVID-19 symptoms to autoimmune responses.},
}
@article {pmid41259430,
year = {2025},
author = {Braga, F and Espinosa, G and Monteiro, A and Milani, M and Paiva, J and Milani, JGPO and Franzoni, L and Stein, R and Cipriano, G and Gurgel, JL and Mourilhe-Rocha, R},
title = {Cardiopulmonary Resilience in Highly Active Individuals: Pre-Post COVID-19 Cardiopulmonary Exercise Testing Analysis.},
journal = {Arquivos brasileiros de cardiologia},
volume = {122},
number = {9},
pages = {e20250094},
pmid = {41259430},
issn = {1678-4170},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; *Exercise Test/methods ; Female ; Retrospective Studies ; Adult ; Oxygen Consumption/physiology ; Middle Aged ; *Exercise Tolerance/physiology ; SARS-CoV-2 ; Time Factors ; },
abstract = {BACKGROUND: The COVID-19 pandemic has affected millions globally, with persistent impacts extending beyond the acute phase. One such effect is post-COVID (long COVID), characterized by symptoms such as fatigue and exercise intolerance lasting more than 60 days. Although regular exercise is associated with reduced risk of severe outcomes, reports of decreased athletic performance after COVID-19 - even among highly active individuals (HAIs) - have raised concerns regarding the long-term effects on physical health. Cardiopulmonary exercise testing (CPET) is a valuable tool to assess exercise intolerance and to investigate the metabolic and ventilatory consequences of COVID-19.<br><br>OBJECTIVES: To evaluate the impact of COVID-19 on cardiopulmonary function in HAIs by analyzing metabolic and ventilatory responses using CPET before and after infection.<br><br>METHODS: CPET data were retrospectively analyzed from HAIs of both sexes. Primary outcomes included changes in peak oxygen uptake (V &#x22c5; O2peak) and ventilatory efficiency (V &#x22c5; E/ V &#x22c5; CO2 slope). Statistical significance was set at 5% (p < 0.05).<br><br>RESULTS: A total of 43 HAIs (72.1% male; 44 &#xb1; 10 years) were included. The median interval between CPETs was 479 days, with testing performed a mean of 44 &#xb1; 27 days after COVID-19. V &#x22c5; O2peak decreased by a mean of 1.5 mL/kg/min (p = 0.017), representing a 3.84% reduction in predicted V &#x22c5; O2peak values (p = 0.045). V &#x22c5; E/ V &#x22c5; CO2 slope increased by 1.2 (p = 0.017).<br><br>CONCLUSION: Although HAIs are not immune to the effects of COVID-19, their high baseline physical activity levels appear to confer substantial cardiopulmonary resilience. Only minimal post-infection alterations were observed, which suggests that maintaining fitness may provide protective benefits against long-term sequelae of COVID-19.},
}
@article {pmid41256779,
year = {2025},
author = {Alemdaroğlu, E and Önal, R and Dizdar, D and Güler, T and Altaş, EU and Kutay Ordu Gökkaya, N},
title = {Continuous versus low-intensity interval aerobic exercise in pulmonary rehabilitation after COVID-19.},
journal = {Turkish journal of physical medicine and rehabilitation},
volume = {71},
number = {3},
pages = {385-394},
pmid = {41256779},
issn = {2587-1250},
abstract = {OBJECTIVES: This study aimed to compare the effectiveness of mild-moderate intensity continuous training (CT) and low-intensity interval moderate-intensity training (LIIT) aerobic exercises in pulmonary rehabilitation after coronavirus disease 2019 (COVID-19).<br><br>PATIENTS AND METHODS: This prospective study was conducted between January 2021 and January 2022. Sixty-three patients (47 males, 16 females; mean age: 54.3&#xb1;11.3 years; range, 25 to 81 years) with one or more residual symptoms following COVID-19 infections were randomly included in the CT (n=33) or LIIT (n=30) groups. Fifteen sessions (60 min, 3-5/week) of aerobic exercise (20-min 40% of peak workload for CT; 40% peak workload with 3-min loaded and 1-min nonloaded intervals for LIIT, with 5 min warm-up and cool-down), breathing, and upper extremity strengthening exercises were applied. Outcome measures were symptom-limited submaximal exercise test, and six-minute walk test (6MWT), the modified Medical Research Council (mMRC) dyspnea scale, modified Borg dyspnea scale, and Borg 6-20 rate of perceived exertion scale, hand grip strength, fat-free mass, Hospital Anxiety and Depression Scale (HADS), and 36-item Short-Form Health Survey.<br><br>RESULTS: The maximum load and time reached during the exercise test, the 6MWT distance, hand grip strength, mMRC, HADS, and SF-36 scores significantly improved in both groups (p<0.05). Resting modified Borg dyspnea scores, heart rate, rate of perceived exertion, and oxygen supplementation requirement decreased significantly in the LIIT group (p<0.05). All posttreatment measures were similar in both groups (p>0.05). The changes in mMRC, resting heart rate, and 6MWT distance were significantly higher in the LIIT group compared to the CT group (p<0.05).<br><br>CONCLUSION: Both CT and LIIT improved functional capacity, dyspnea, tachycardia, depression, and quality of life measures safely and effectively in COVID-19 survivors with residual symptoms. Patients with poor clinical status who cannot tolerate CT after an acute pulmonary condition such as COVID-19 may benefit from LIIT.},
}
@article {pmid41256693,
year = {2025},
author = {Arish, M and Chaudhuri, AS and Tang, J and Narasimhan, H and Fang, A and Tang, J and Wei, X and Li, C and Cheon, IS and Qian, W and Naz, F and Almeida-Santos, G and Patrick Young, S and Parimon, T and Michael Shim, Y and Vassallo, R and Chen, P and Sun, J},
title = {Targeting a macrophage stemness factor to mitigate diseases post respiratory viral infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41256693},
issn = {2692-8205},
support = {R01 HL152293/HL/NHLBI NIH HHS/United States ; F31 HL170746/HL/NHLBI NIH HHS/United States ; T32 AI007496/AI/NIAID NIH HHS/United States ; R01 AI176171/AI/NIAID NIH HHS/United States ; R01 HL132177/HL/NHLBI NIH HHS/United States ; R01 AG069264/AG/NIA NIH HHS/United States ; R01 AI147394/AI/NIAID NIH HHS/United States ; R01 HL170961/HL/NHLBI NIH HHS/United States ; R01 HL167202/HL/NHLBI NIH HHS/United States ; R01 AI112844/AI/NIAID NIH HHS/United States ; P01 HL108793/HL/NHLBI NIH HHS/United States ; R01 HL159953/HL/NHLBI NIH HHS/United States ; R01 HL132287/HL/NHLBI NIH HHS/United States ; R01 HL155759/HL/NHLBI NIH HHS/United States ; R21 AI163753/AI/NIAID NIH HHS/United States ; R01 HL159675/HL/NHLBI NIH HHS/United States ; R01 AI154598/AI/NIAID NIH HHS/United States ; },
abstract = {Tissue-resident alveolar macrophages (AMs) rely on intrinsic stem-like programs for self-renewal and maintenance, yet the transcriptional networks that support these functions and their relevance to post-viral lung disease remain largely unknown. Here, we identify TCF4 (Tcf7l2) as a critical transcription factor that governs AM maturation and stemness. Loss of TCF4 impaired AM proliferation, shifted their identity toward a pro-inflammatory phenotype, and exacerbated host morbidity following influenza or SARS-CoV-2 infection. Conversely, enforced TCF4 expression promoted the expansion of mature AMs, and supported lung recovery, thereby protecting against severe acute viral disease. Mechanistically, TCF4 antagonized β-catenin-driven inflammatory transcription while preserving oxidative phosphorylation, defining a reciprocal regulatory axis essential for AM function. Notably, respiratory viral infections and exuberant interferon signaling suppressed TCF4 expression, which remains chronically reduced in murine and human lungs with post-COVID fibrosis. This downregulation is associated with persistent KRT8[hi] dysplastic epithelium and collagen deposition. Moreover, aging diminished TCF4 levels and enforced TCF4 expression dampened age-associated decline of AM self-renewal. Furthermore, in vivo TCF4 overexpression after viral clearance enhanced mature AM accumulation, promoted lung epithelium regeneration, attenuated chronic tissue fibrosis and restored pulmonary physiologial function in aged lungs in a model of persistent pulmonary fibrosis post-acute viral infection. These findings have established TCF4 as a key regulator of AM stemness and identified a promising therapeutic target for long COVID and related chronic lung diseases through the modulation of embryonic-derived macrophage regenerative capacity by targeting TCF4.},
}
@article {pmid41255761,
year = {2025},
author = {Sularea, VM and Townsend, L and Reid, C and Atanasescu, AV and Dyer, AH and Giangrazi, F and Lawrence, RR and Sivan, M and Moran, B and Doherty, DG and Conlon, NP and Long, A and O'Farrelly, C},
title = {Digitally Assessed Long COVID Symptomatology Is Associated With Lymphocyte Mitochondrial Dysfunction and Altered Immune Potential.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf447},
pmid = {41255761},
issn = {2328-8957},
support = {/WT_/Wellcome Trust/United Kingdom ; },
abstract = {BACKGROUND: Postacute sequelae of SARS-CoV-2 infection, also known as long COVID (LC), is a complex and heterogenous condition affecting millions worldwide with a poorly understood underlying pathology. Although metabolic dysregulations have been described in LC, it remains unclear whether circulating immune cells exhibit immunometabolic alterations.<br><br>METHODS: We conducted a detailed clinical, immunologic, and mitochondrial analysis on 27 patients with LC and 27 who recovered from COVID-19 and were healthy. Symptom burden and severity were assessed and quantified via a digital platform with the modified COVID-19 Yorkshire Rehabilitation Scale. Mitochondrial function of circulating immune cell populations (lymphocytes and monocytes) was analyzed by measuring mitochondrial mass and mitochondrial membrane potential. Production of 11 cytokines after whole blood stimulation with bacterial and viral agonists was measured by multiplex immunoassay. Relationships between mitochondrial and immune parameters with LC symptoms were investigated.<br><br>RESULTS: Patients with LC exhibited significant symptom burden, with worsening across all symptom domains as compared with their health state before SARS-CoV-2 infection. They also had a decreased mitochondrial membrane potential of CD56[bright] natural killer cells, particularly in patients experiencing dizziness, whereas reduced mitochondrial membrane potential in CD4+ lymphocytes was found in patients with worsening breathlessness. Upon LPS stimulation, patients with LC demonstrated significantly lower IFN-&#x3b3; production. In response to viral ligand R848, impaired IFN-&#x3b2; and IL-10 responses were associated with worsening cough and executive functions.<br><br>CONCLUSIONS: Symptom severity in LC is associated with immune cell mitochondrial dysfunction and altered cytokine responses, highlighting potential disease biomarkers and targets for future therapeutic strategies.},
}
@article {pmid41254881,
year = {2025},
author = {Kartal Öztürk, G and Böncüoğlu, E and Kıymet, E and Şahinkaya, &#x15e; and Cem, E and Yılmaz Çelebi, M and Kara, AA and Karkıner, C&#x15e; and Bayram, SN and Devrim, &#x130;},
title = {Long-term follow-up of children after COVID-19 infection and monitoring pulmonary functions.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {67},
number = {1},
pages = {e70274},
doi = {10.1111/ped.70274},
pmid = {41254881},
issn = {1442-200X},
mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; Child ; Male ; Female ; Adolescent ; Follow-Up Studies ; Respiratory Function Tests ; Child, Preschool ; Infant ; Prospective Studies ; *Lung/physiopathology ; },
abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus 2 is now part of our lives. Many children still experience post-COVID respiratory conditions and require evaluation and follow-up.<br><br>METHODS: Children referred to the Pediatric Pulmonology Department between 2021 and 2022, due to a history of COVID-19 pneumonia with/without comorbid disease and respiratory complaints after COVID-19, were prospectively followed up with pulmonary function tests at 3, 6, and 12&#x2009;months.<br><br>RESULTS: The median age of 138 children was 14&#x2009;years (1-18), 42 (30.4%) had comorbid conditions, and 40 (28.9%) had a history of COVID-19 pneumonia. Respiratory symptoms after infection persisted in approximately 62% of children, and 28% of children who had no symptoms before infection were diagnosed with asthma (N&#x2009;=&#x2009;18, 13%), allergic rhinitis (N&#x2009;=&#x2009;5), anxiety and tic disorder (N&#x2009;=&#x2009;4), and other diseases (N&#x2009;=&#x2009;4). At admission, pulmonary function abnormalities were detected in 12% (N&#x2009;=&#x2009;4 obstructive ventilatory pattern, N&#x2009;=&#x2009;6 restrictive, and N&#x2009;=&#x2009;2 mixed). Pulmonary functions were similar in children with and without persistent respiratory complaints (PRCs). At the 12-month follow-up, there were three children (2.1%) with PRC, and pulmonary function anomalies persisted in five children. A significant increase in pulmonary function was observed in both children with and without PRC. FEF25-75, the indicator of small airways, was lower in children with PRC.<br><br>CONCLUSIONS: This study suggested that COVID-19 may have affected pulmonary function in children independently of respiratory symptoms and that this effect may be more severe in children with PRC. It is necessary to follow up and research examination and early intervention methods for post-COVID conditions.},
}
@article {pmid41254361,
year = {2025},
author = {Stiles, LE and Larsen, NW and Eastin, EF and Miglis, MG},
title = {Response to letter by Zadeh et al. regarding "Chronic autonomic symptom burden in long-COVID: a follow-up cohort study".},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {},
number = {},
pages = {},
pmid = {41254361},
issn = {1619-1560},
}
@article {pmid41253410,
year = {2025},
author = {Volckaerts, T and Ruttens, D and Quadflieg, K and Burtin, C and Cops, D and De Soomer, K and Roelant, E and Verhaegen, I and Daenen, M and Criel, M and Vissers, D and Lapperre, T},
title = {Improved functional exercise capacity after primary care pulmonary rehabilitation in patients with long COVID (PuRe-COVID): a pragmatic randomised controlled trial.},
journal = {BMJ open respiratory research},
volume = {12},
number = {1},
pages = {},
pmid = {41253410},
issn = {2052-4439},
mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/rehabilitation/physiopathology/complications ; *Exercise Tolerance/physiology ; Primary Health Care ; Adult ; Walk Test ; SARS-CoV-2 ; *Exercise Therapy/methods ; Aged ; Hand Strength ; Treatment Outcome ; Fatigue ; Dyspnea ; Patient Reported Outcome Measures ; },
abstract = {BACKGROUND: Pulmonary rehabilitation (PR) improves physical status and symptoms in patients with long COVID, but access to specialised hospital-based centres is challenging. This trial studied the effect of primary care PR on functional exercise capacity and symptoms in patients with long COVID.<br><br>METHODS: In this pragmatic randomised controlled trial (PuRe-COVID), patients with long COVID were randomised to a 12-week stepwise PR programme in primary care, or to a control group without PR. The primary end point was change in 6&#x2009;min walk distance (6MWD) from baseline to 12 weeks. Additional outcomes, measured at 6, 12, 24 and 36 weeks, included patient-reported outcomes, physical activity, maximal inspiratory (MIP) and expiratory pressures and hand grip strength.<br><br>RESULTS: In total, 76 patients were randomised (PR/control group (n=39/37); mean age 49&#xb1;13&#x2009;years). The change in 6MWD at 12 weeks was estimated to be +39&#x2009;m in the PR group compared with the control group (95%&#x2009;CI (18 to 59), p<0.001). Furthermore, a decrease in Checklist Individual Strength (CIS)-fatigue was found for the PR group (-6 points; 95%&#x2009;CI (-10 to -2), p=0.011). At 12 weeks, patients in the intervention group were more likely to have a clinically significant improvement in 6MWD (OR 5.7, 95%&#x2009;CI (2.0 to 16.1), p=0.001), CIS-fatigue (OR 3.8, 95%&#x2009;CI (1.2 to 12.0), p=0.020), MIP (OR 3.7, 95%&#x2009;CI (1.05 to 12.7), p=0.036) and modified Medical Research Council dyspnoea score (OR 5.2, 95%&#x2009;CI (1.6 to 16.4), p=0.003).<br><br>CONCLUSIONS: Primary care stepwise individual PR may improve functional exercise capacity, fatigue and dyspnoea in patients with long COVID. It therefore may be a promising treatment option in primary care for patients with long COVID experiencing fatigue and/or respiratory symptoms.<br><br>TRIAL REGISTRATION NUMBER: NCT05244044.},
}
@article {pmid41253056,
year = {2025},
author = {Ouyang, T and Huang, Z and Wei, S and Yang, J and Voskrebenzev, A and Vogel-Claussen, J and Guo, S and Yang, Q},
title = {Longitudinal assessment of pulmonary perfusion and ventilation defects in long COVID: A one-year study using phase-resolved functional lung (PREFUL) MRI.},
journal = {Computers in biology and medicine},
volume = {199},
number = {},
pages = {111316},
doi = {10.1016/j.compbiomed.2025.111316},
pmid = {41253056},
issn = {1879-0534},
mesh = {Humans ; *COVID-19/diagnostic imaging/physiopathology ; Female ; Male ; Aged ; *Magnetic Resonance Imaging/methods ; *Lung/diagnostic imaging/physiopathology ; Middle Aged ; Longitudinal Studies ; SARS-CoV-2 ; Prospective Studies ; *Pulmonary Ventilation ; },
abstract = {RATIONALE AND OBJECTIVES: The long-term trajectories of pulmonary perfusion and ventilation after recovery from SARS-CoV-2 infection are lacking. This study aims to longitudinally assess changes in perfusion (QDP) and ventilation (VDP) defects using phase-resolved functional lung (PREFUL) MRI in post-SARS-CoV-2 infection.<br><br>MATERIALS AND METHODS: This prospective study was conducted from January to May 2023 and included non-hospitalized, COVID-19-positive patients with pneumonia or symptoms suggestive of pneumonia, as well as healthy controls. Serial MRI scans were performed at acute, 3, 6, and 12 months after symptom onset, and healthy controls underwent only one MRI scan. Longitudinal comparisons of QDP and VDPCombined were employed by linear mixed-effects models. Long COVID was defined as persistent SARS-CoV-2 symptoms for at least three months, with associated factors identified through logistic regression.<br><br>RESULTS: A total of 60 participants (median age 68.5 years; 30 female) were included. VDPCombined was 21&#xa0;%, 18&#xa0;%, 16&#xa0;%, and 13&#xa0;% at the acute phase, 3 months, 6 months, and 12 months, respectively, with a significant difference observed in the longitudinal comparison (P&#xa0;=&#xa0;0.034). Moreover, at 12 months, VDPCombined showed no significant difference compared to the healthy control (P&#xa0;=&#xa0;0.280). QDP also decreased (42&#xa0;%, 36&#xa0;%, 35&#xa0;%, and 19&#xa0;% at acute, 3 months, 6 months, and 12 months, respectively; P&#xa0;<&#xa0;0.001), but remained significantly higher than in healthy controls at 12 months (P&#xa0;<&#xa0;0.001). At follow-up, 55&#xa0;% of participants (33 of 60) had long COVID, with higher acute-phase QDP associated with increased odds of developing long COVID (odds ratio, 1.20; P&#xa0;=&#xa0;0.001).<br><br>CONCLUSION: Pulmonary perfusion impairment persists up to 12 months following SARS-CoV-2 infection. Severe perfusion defects during acute phase are a risk factor for the development of long COVID.},
}
@article {pmid41252855,
year = {2026},
author = {Oh, S and Wijaya, J},
title = {Predictive surveillance and diagnosis of COVID-19: An integrative machine learning and wastewater multi-omics approach.},
journal = {Water research},
volume = {289},
number = {Pt B},
pages = {124981},
doi = {10.1016/j.watres.2025.124981},
pmid = {41252855},
issn = {1879-2448},
mesh = {*COVID-19/diagnosis/epidemiology/virology ; *Wastewater/virology ; *Machine Learning ; Humans ; *SARS-CoV-2/genetics/isolation &amp; purification ; Republic of Korea/epidemiology ; Multiomics ; },
abstract = {COVID-19 has had major global impacts, highlighting the importance of robust predictive surveillance and diagnostic systems to ensure effective public health responses. Traditional surveillance methods based on passive case counting and diagnostic testing of individual patients often suffer from delays and resource constraints, preventing timely responses. This study proposed an integrative framework integrating machine learning (ML)-derived predictive surveillance with wastewater-based diagnosis, aiming to predict temporal trends in Korea and identify disease-causing agents. The ML model utilized crowdsourced COVID-19-related keywords, climatic, and environmental data, optimized via model selection and feature selection. The integrated data-driven model predicted COVID-19 cases over three years more accurately than those using single source data (i.e., baseline model). The explainable AI technique (i.e., helping to inform how the model made those predictive decisions) identified six keywords (reducing phlegm, throat pain, long COVID-19, sore throat, COVID-19 self-kit, and COVID-19 kit) as robust predictors of disease trends. In a proof-of-concept experiment, wastewater-based genotyping of disease-causing agents and affected human communities in sewershed areas was conducted. Metatranscriptomics of municipal wastewater was conducted to identify COVID-19 viral variants, evolutionarily related to those clinically isolated strains, distinguishable from conventional diagnostic testing of individual patients. Wastewater-derived metagenomics was also performed to assess genomic variation in the affected human populations. The integrative framework proposed in this study offers a rapid, cost-effective approach for the surveillance and diagnosis of COVID-19 and other infectious diseases, thus strengthening or complementing existing health systems.},
}
@article {pmid41249654,
year = {2025},
author = {Azola, A and Dastgheyb, RM and Easter, R and Parker, H and Della Penna, C and Santiuste, I and Schultz, H and Ehrenspeck, A and Veenhuis, R and Rubin, LH},
title = {Putting the PASC Score to the Test: Clinical vs. Statistical Accuracy in Long COVID Diagnosis.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41249654},
issn = {1525-1497},
support = {RF1 MH133411/MH/NIMH NIH HHS/United States ; },
abstract = {OBJECTIVE: To validate the RECOVER Post-Acute Sequelae of SARS-CoV-2 infection (PASC) score in a cohort of patients who develop long COVID (LC) or fully recover while iteratively improving the tool's sensitivity and specificity.<br><br>METHODS: A cross-sectional study in 130 LC patients followed at LC clinics in Baltimore, MD, USA, who met the National Academies of Sciences, Engineering, and Medicine (NASEM) 2024 LC definition, and 60 SARS-CoV-2 exposed but fully recovered individuals. LC participants were required to have at least one neuropsychiatric symptom. Participants completed comprehensive surveys and questionnaires assessing symptoms based on published methods to determine PASC score. Using the NASEM 2024 LC definition as the "true" condition, we compared evaluation metrics for the RECOVER PASC score cutoff (PASC&#x2009;>&#x2009;12) and the presence of individual/multiple symptoms. Evaluation metrics (e.g., sensitivity, specificity, F1) were calculated based on these classifications for the overall PASC score and symptom combinations.<br><br>RESULTS: The LC cohort (n&#x2009;=&#x2009;130) had a mean age of 47.2&#xa0;years and was predominantly female (72%), White (79%), and well-educated (77%&#x2009;>&#x2009;16&#xa0;years). Controls (n&#x2009;=&#x2009;60) were similar demographically. LC diagnosis and PASC scores were significantly associated (&#x3c7;[2]&#x2009;=&#x2009;102.99, P&#x2009;<&#x2009;0.001). The PASC score showed excellent specificity (100%) and positive predictive value (PPV; 100%) albeit limited sensitivity (80%), missing 20% of participants with LC. We found that loss of smell/taste, post-exertional malaise, or lack of sexual desire or capacity demonstrated 94% sensitivity, 92% specificity, and 96% PPV, 87% NPV, and an F1 score of 0.949.<br><br>CONCLUSION: Validation of the RECOVER PASC supports its utility and highlights the need for ongoing refinement of the LC definition. We call for national efforts to develop readily implementable clinical tools for LC diagnosis.},
}
@article {pmid41249484,
year = {2025},
author = {Eisinger, RW and Breen, JJ and Beigel, J and Geerling, E and Gerberding, J and Taubenberger, JK},
title = {Progress on the pathway to long COVID treatments.},
journal = {Nature immunology},
volume = {26},
number = {12},
pages = {2126-2129},
pmid = {41249484},
issn = {1529-2916},
}
@article {pmid41249167,
year = {2025},
author = {Thaweethai, T and Donohue, SE and Martin, JN and Hornig, M and Mosier, JM and Shinnick, DJ and Ashktorab, H and Atieh, O and Blomkalns, A and Brim, H and Chen, Y and Cortez, MM and Erdmann, NB and Flaherman, V and Goepfert, P and Goldman, JD and Hamburg, NM and Han, JE and Heath, JR and Jacoby, V and Jolley, SE and Kelly, JD and Kelly, SW and Kim, C and Krishnan, JA and Letts, R and Levitan, EB and Modes, ME and McComsey, GA and Metz, TD and Mullington, JM and Ofotokun, I and Okumura, MJ and Paredes, CC and Patterson, TF and Peluso, MJ and Reece, R and Sherif, ZA and Simhan, HN and Simmons, C and Singh, U and Taylor, BS and Taylor, BD and Trinity, JD and Troxel, AB and Utz, PJ and Vasey, AJ and Weinberger, E and Wiley, Z and Wisnivesky, J and Yee, LM and Horwitz, L and Foulkes, AS and Levy, BD and , },
title = {Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9557},
pmid = {41249167},
issn = {2041-1723},
support = {OTA OT2HL161841, OT2HL161847, OT2HL156812, OT2HL162087, and R01 HL162373//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; I01 RX003810/RX/RRD VA/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Post-Acute COVID-19 Syndrome/epidemiology/pathology/therapy/virology ; Male ; Female ; Adolescent ; Adult ; Middle Aged ; Prospective Studies ; Longitudinal Studies ; Cohort Studies ; *SARS-CoV-2/physiology ; Reinfection/pathology ; Viral Load ; United States/epidemiology ; },
abstract = {Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.},
}
@article {pmid41248356,
year = {2025},
author = {Nejatinamini, S and Charlton, C and Harman, S and Kanji, JN and Kellner, JD and Lines, K and Murdoch, K and Powell, W and Roberts, J and Rosner, W and Shen-Tu, G and Tipples, G and Xu, JY and Vena, JE},
title = {COVID-19 antibody testing study: a nested substudy within Alberta's Tomorrow Project (ATP) in Alberta, Canada.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e101336},
pmid = {41248356},
issn = {2044-6055},
mesh = {Humans ; Alberta/epidemiology ; Middle Aged ; *COVID-19/epidemiology/diagnosis/immunology ; Female ; Male ; Adult ; Aged ; Prospective Studies ; *SARS-CoV-2/immunology ; *Antibodies, Viral/blood ; *COVID-19 Serological Testing ; Longitudinal Studies ; },
abstract = {PURPOSE: The Alberta's Tomorrow Project (ATP) prospective cohort study was established in 2000 to investigate the causes of cancer and chronic disease. The cohort consists of almost 55 000 participants aged 35-69 years at the time of recruitment. From 2020 to 2022, ATP conducted a longitudinal substudy, the COVID-19 Antibody Testing (CAT) study, nested in this existing cohort, to understand the spread and impact of the SARS-CoV-2. In this cohort profile, we describe the CAT study design, recruitment and initial findings.<br><br>PARTICIPANTS: In this prospective cohort substudy, ~4000 participants completed online surveys and provided blood samples at a study centre every 4&#x2009;months for 1 year, across four cities in Alberta, Canada. The study was launched on a rolling basis beginning in September 2020 and data collection was completed in May 2022. The surveys collected information on health and lifestyle factors, COVID-19 (testing, symptoms, vaccination, public health recommendations) and impacts of the pandemic (including economic, health services, mental health). Blood samples were tested for antinucleocapsid and antispike protein SARS-CoV-2 antibodies.<br><br>FINDINGS TO DATE: A total of 4102 participants consented and attended a study centre at baseline, and almost 90% of these completed the study. Overall, participants were aged 61&#xb1;10 years, 60% female, 12% came from rural areas, 45% had at least a bachelor's degree, 24% reported a household income <$C75 000 and 39% were retired. About 15% of participants tested positive for antibodies induced by a SARS-CoV-2 infection over the course of the study, and about 18% of those who were infected reported long COVID (persistent symptoms for >4 weeks). By the end of the study, 96% of participants had received at least one COVID-19 vaccine dose. Through investigating other outcomes, it was observed that participants under 50 years of age were more likely to be assessed to have mild or moderate-to-severe anxiety and depressive symptoms compared with older participants. In addition, approximately 15% of participants reported a moderate to major impact on their ability to meet financial obligations.<br><br>FUTURE PLANS: Serology results, together with health, lifestyle and sociodemographic data, and the continued follow-up of these participants as part of the broader ATP cohort study (planned through 2065), will provide opportunities to investigate the long-term sequelae of COVID-19 infection as well as the broader impacts of the pandemic on physical, mental and emotional health. Data are available to researchers on request through the ATP access process.},
}
@article {pmid41248018,
year = {2025},
author = {Wu, J and Xie, N and Meng, W and Ma, Y and Li, Z and Zeng, H and Chen, Y},
title = {Long COVID and symptom persistence in post-discharge omicron patients: Insights into C-reactive protein.},
journal = {Chronic illness},
volume = {21},
number = {4},
pages = {504-517},
doi = {10.1177/17423953251387913},
pmid = {41248018},
issn = {1745-9206},
mesh = {Humans ; *C-Reactive Protein/analysis/metabolism ; Male ; *COVID-19/mortality/blood/complications/epidemiology ; Female ; Middle Aged ; Aged ; SARS-CoV-2 ; Patient Discharge ; Fatigue/epidemiology ; Risk Factors ; Length of Stay/statistics &amp; numerical data ; Biomarkers/blood ; Adult ; Hospitalization ; },
abstract = {ObjectivesLong-term health effects of Omicron infection, particularly persistent Long COVID in hospitalized patients, require further investigation.MethodsPatients hospitalized for Omicron infection (Dec 2022-Mar 2023) underwent follow-ups at 6 months and 1 year post-discharge. Univariate/multivariate analyses identified mortality predictors, symptom trends, and optimal CRP levels (mg/L) thresholds.ResultsAmong 410 patients, 59 died; mortality predictors included age (OR = 1.070), ICU admission (OR = 15.748), diabetes (OR = 3.363), antibacterial use (OR = 0.283), and lymphocyte count (OR = 0.099). At 6 months, 86.0% reported ≥1 symptom (83.5% at 1 year). Fatigue, cough, and snoring were most common, with symptom counts decreasing significantly over time. Symptomatic patients had longer hospital stays (P = 0.022), lymphopenia (P = 0.036), and elevated CRP levels (P = 0.010). A CRP level ≥15.38 mg/L was associated with a greater risk of symptom persistence and may serve as a potential predictive marker.ConclusionHospitalized Omicron survivors experience prolonged symptoms, with ICU admission, age, and diabetes as key mortality risks. Fatigue and snoring may persist despite overall improvement. Elevated CRP and prolonged hospitalization in symptomatic patients underscore the need for long-term monitoring and interventions targeting high-risk groups.},
}
@article {pmid41247781,
year = {2025},
author = {Henrich, TJ and Montgomery, CP and Graf, J and Ismail, N and Mohandas, S and Suthar, MS and Brim, H and Coffin, JM and Pagaria, A and Guzmán Rivera, J and Vudali, U and Keim, P and Zhong, G and McGrath, R and Edwards, B and García-Sastre, A and Gennaro, ML},
title = {The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {41247781},
issn = {2050-084X},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; *Coinfection/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Bacterial Infections/complications ; },
abstract = {A major health challenge resulting from the COVID-19 pandemic is the manifestation of post-acute sequelae of SARS-CoV-2 (PASC). PASC (or long COVID) is a collective term used for clinical symptoms, various pathologies, and life-quality-changing functional impairment that persist for months to years after the initial SARS-CoV-2 infection. The mechanisms underlying PASC are not understood, although advances have been made in identifying factors that may contribute to long-term pathology. Recent data have emerged, showing an association between SARS-CoV-2 viral persistence and non-SARS-CoV-2 infections (pre-existing, viral reactivation, or new infections) in facilitating or mediating PASC. However, the heterogeneous nature and timing of co-infections have made it challenging to understand, interpret, and contextualize their contribution to PASC. Here, we summarize the impact of potential viral, bacterial, and fungal infections on SARS-CoV-2 pathogenesis, with a focus on their possible roles in the development of PASC. We also provide a framework to understand the mechanisms of PASC and inform basic, translational, and clinical research initiatives, including RECOVER, a large and ongoing research initiative to understand, treat, and prevent long COVID.},
}
@article {pmid41245391,
year = {2025},
author = {Duarte, ACB and Lafetá, ML and Verrastro, CGY and Mancuso, FJ and Tanni, SE and Albuquerque, ALP and Sperandio, PA and Oliveira, RKF and Ota-Arakaki, JS and Ferreira, EVM},
title = {Chronic Dyspnea and Residual Pulmonary Vascular Sequelae After COVID-19 Pulmonary Embolism: A Retrospective Analysis.},
journal = {Pulmonary circulation},
volume = {15},
number = {4},
pages = {e70198},
pmid = {41245391},
issn = {2045-8932},
abstract = {During the COVID-19 pandemic, Brazil was one of the most affected countries. Patients presented higher risk of acute venous thromboembolism (VTE), in particular, pulmonary embolism (PE). However, long-term implications of these events remain unknown. A retrospective analysis from the FENIX study was conducted, and patients with COVID-19-related VTE during hospitalization were included. Further analysis, up to 6 months after the acute event, was performed exclusively in patients with PE. Persistence of dyspnea and exercise intolerance was evaluated through imaging, rest, and exercise functional tests. Cumulative incidence of VTE during hospitalization among COVID-19 survivors followed at the outpatient clinic was 17.7% (n = 75/423) and of acute PE was 9.9% (n = 42/423). Patients with PE were mostly male (66%), 56 ± 16 years old, and mainly classified as intermediate-low risk (74%). Dyspnea (mMRC≥ 1) up to 6 months of PE was present in 56% (n = 19/34), with a borderline association with parenchymal lung sequelae on chest CT scan (p = 0.069). Symptomatic patients upon follow-up presented lower FEV1 and FVC, as well as increased peak VD/VT ratio and ventilatory inefficiency. No signs of pulmonary hypertension (PH) were identified on echocardiogram (ECHO) and cardiopulmonary exercise testing (CPET). Persistence of dyspnea among post-PE related to COVID-19 was high. However, no cases of PH were found; follow-up findings may be related to pulmonary parenchymal and microvascular injury. Also, we cannot exclude association with long-COVID, in which pathophysiological mechanisms are multifactorial, involving chronic inflammatory changes and multiorgan dysfunction, highlighting the need for comprehensive evaluation of exercise intolerance through invasive CPET.},
}
@article {pmid41245100,
year = {2025},
author = {Ramachandran, R and Sathar, F and Mokome, P and Mathabela, N and Mahlase, E and Charalambous, S and Rachow, A and Glover, NA and Ivanova, O},
title = {Acceptability and feasibility of a group intervention for long COVID in Johannesburg, South Africa: a mixed-method study.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1666387},
pmid = {41245100},
issn = {2813-0146},
abstract = {BACKGROUND: COVID-19 affected 777 million people globally, with 7.1 million deaths. In Africa, 9.6 million cases and 176,000 deaths were reported. Long COVID, a significant consequence of the COVID-19, presented by chronic symptoms, affects the physical and mental health, thereby impacting the quality of life. While high-income countries implemented rehabilitation programs for managing long COVID symptoms, low- and middle-income countries faced healthcare disparities. In South Africa, limited multidisciplinary interventions were evident. This study aimed to assess the acceptability and feasibility of an 8-week rehabilitation and self-management program for long COVID using mixed-methods approach in Johannesburg.<br><br>METHODS: Patients and hospital staff who suffered from at least one symptom of long COVID for a period of two months and who consented to participate in the intervention were recruited from Tembisa Provincial Tertiary Hospital. The recruitment was from July to October 2023. Questionnaires were administered and interviews with selected participants were conducted to assess the acceptability and feasibility of the intervention. A descriptive analysis was carried out for the quantitative data, and a deductive thematic analysis was used for the interviews.<br><br>RESULTS: The participants had positive perceptions towards the design of the intervention, delivery, materials used and support by research staff and external consultants such as dietitians, physiotherapists, and psychologists. The participants stated that the intervention had improved their knowledge of long COVID and increased their self-confidence. Major barriers related to the intervention perceived by the participants were infrastructure, time and language. Recommendations from the participants included expanding the intervention at the community level and extending the duration of the intervention beyond 8-weeks.<br><br>CONCLUSION: This pilot intervention, that aimed to manage the symptoms of long COVID, was well accepted by the participants and achieved its intended outcome. Similar interventions are required at the clinical as well as community levels.},
}
@article {pmid41244103,
year = {2025},
author = {Yue, Y and Han, X and Chen, Q and Dai, L and Ai, Q and Zhang, Z and Ma, F and Gao, J},
title = {The effect of pulmonary rehabilitation for post-acute sequelae of SARS-CoV-2 infection in patients: a systematic review and meta-analysis.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1634351},
pmid = {41244103},
issn = {2673-6861},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, are characterized by persistent symptoms such as fatigue, dyspnea, and reduced functional capacity. Pulmonary rehabilitation (PR) is recommended for chronic respiratory conditions, but its effectiveness in PASC, particularly across different delivery modes, remains uncertain.<br><br>OBJECTIVE: To assess the impact of PR, including telerehabilitation and in-person modalities, on physical function, dyspnea, pulmonary function, fatigue, and quality of life in patients with PASC.<br><br>METHODS: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science from inception to March 25 for controlled clinical trials assessing the effects of PR in PASC patients. Two independent reviewers performed study selection and data extraction. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and data were analyzed using Review Manager (RevMan) 5.4.1. Effect sizes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI).<br><br>RESULTS: Ten randomized controlled trials involving 673 participants were included. Most studies were judged to have a moderate risk of bias. Compared with usual care, PR significantly improved six-minute walk distance (MD: 76.85 meters; 95% CI: 57.35-96.36; p&#x2009;<&#x2009;0.001), maximal inspiratory pressure (MD: 17.63&#x2005;cmH&#x2082;O; 95% CI: 4.50-30.76; p&#x2009;=&#x2009;0.009), fatigue (SMD: -1.15; 95% CI: -1.83 to -0.48; p&#x2009;<&#x2009;0.001), and quality of life (SMD: 1.73; 95% CI: 0.56-2.91; p&#x2009;=&#x2009;0.004). No statistically significant improvement was found for dyspnea (MD: -0.41; 95% CI: -1.51 to -0.68; p&#x2009;=&#x2009;0.46). Subgroup analyses showed no significant differences between telerehabilitation and in-person PR across all outcomes, including exercise capacity (p&#x2009;=&#x2009;0.84), dyspnea (p&#x2009;=&#x2009;0.86), fatigue (p&#x2009;=&#x2009;0.93), and quality of life (p&#x2009;=&#x2009;0.44).<br><br>CONCLUSIONS: PR improves physical and functional outcomes in patients with PASC. Telerehabilitation offers a clinically equivalent alternative to in-person PR, supporting its broader implementation.},
}
@article {pmid41242093,
year = {2026},
author = {Alonso-Domínguez, J and González-Nóvoa, JA and López-López, A and Martínez-Barros, I and Pérez-González, A and Leiro-Fernández, V and Aguayo-Arjona, J and Teijeira, S and Veiga, C and Poveda, E},
title = {Artificial intelligence-based identification of key risk factors for long COVID from early clinical data.},
journal = {Journal of infection and public health},
volume = {19},
number = {1},
pages = {103051},
doi = {10.1016/j.jiph.2025.103051},
pmid = {41242093},
issn = {1876-035X},
mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Female ; Male ; Risk Factors ; Middle Aged ; *Artificial Intelligence ; SARS-CoV-2 ; Biomarkers/blood ; Adult ; Aged ; Machine Learning ; ROC Curve ; Bayes Theorem ; },
abstract = {INTRODUCTION: Long COVID, a complex condition characterized by persistent symptoms following SARS-CoV-2 infection, has become a significant public health concern. Early identification of individuals at risk for long COVID is crucial for effective management. This study explores the potential of biochemical and clinical markers, alongside machine learning (ML) models, to predict long COVID development using data from the first 72 h post-admission.<br><br>METHODS: We analyzed clinical and laboratory data from 394 individuals diagnosed with SARS-CoV-2. A predictive model for long COVID was developed using machine learning algorithms, particularly XGBoost, to identify key biomarkers associated with the development of long COVID symptoms at 3 months post-infection. The model hyperparameters were optimized using Bayesian optimization techniques, and variable importance was assessed using SHAP values.<br><br>RESULTS: The predictive model achieved an area under the receiver operating characteristic curve (AUC-ROC) of 0.732, indicating moderate discriminatory power. Key variables identified included hemoglobin levels, oxygen saturation, weight, C-reactive protein (CRP), activated partial thromboplastin time (APTT), sodium, type of pulmonary infiltrates, and sex. Hemoglobin levels were the only statistically significant variable (p&#x202f;=&#x202f;0.015) between those who developed long COVID and those who did not. Despite these findings, the model showed moderate overall accuracy (63.9&#x202f;%) but excelled in recall (78.6&#x202f;%), highlighting its potential in clinical settings for early identification of high-risk patients.<br><br>CONCLUSIONS: Our study demonstrates the feasibility of using machine learning to predict long COVID based on early clinical and laboratory data. While individual biomarkers alone may have limited predictive value, their combination enhances risk assessment for long COVID. Future studies should focus on refining the model and validating it in broader populations, including those with milder COVID-19 forms, to improve its accuracy and clinical utility.},
}
@article {pmid41241149,
year = {2025},
author = {Park, WH},
title = {The mitochondrial nexus: Dysfunction, inhibition, and therapeutic frontiers in lung disease.},
journal = {Respiratory medicine},
volume = {250},
number = {},
pages = {108506},
doi = {10.1016/j.rmed.2025.108506},
pmid = {41241149},
issn = {1532-3064},
mesh = {Humans ; *Mitochondria/metabolism/physiology ; *Lung Diseases/metabolism/physiopathology/therapy ; COVID-19/metabolism ; Reactive Oxygen Species/metabolism ; SARS-CoV-2 ; Mitophagy/physiology ; Pulmonary Disease, Chronic Obstructive ; Energy Metabolism ; Antioxidants/therapeutic use ; },
abstract = {Mitochondria are increasingly recognized as central arbiters of cellular fate, placing them at the nexus of pulmonary health and disease. Beyond their canonical role in adenosine triphosphate (ATP) synthesis, these organelles are critical hubs for redox signaling, metabolic homeostasis, and programmed cell death. Mitochondrial dysfunction-a multifaceted condition characterized by impaired bioenergetics, excessive reactive oxygen species (ROS) production, aberrant dynamics, and defective quality control via mitophagy-is a unifying pathogenic feature in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH). This dysfunction is also a critical determinant of severity in acute conditions like acute lung injury (ALI) and COVID-19 and is a key mechanistic driver of Long COVID. This review synthesizes the core mechanisms of mitochondrial impairment, delineates their specific contributions to this spectrum of pulmonary pathologies, and discusses the burgeoning field of mitochondria-targeted therapeutics. Strategies ranging from targeted antioxidants and metabolic modulators to novel regenerative approaches like mitochondrial transplantation are highlighted, with an expanded discussion on their limitations, challenges, and clinical implications. By framing mitochondrial integrity as a critical determinant of pulmonary disease, we underscore a pivotal axis for future diagnostic and therapeutic innovation.},
}
@article {pmid41239971,
year = {2025},
author = {Sun, H and Mullington, JM and Thomas, RJ},
title = {Post-Infection Sleep Syndrome: Long COVID as an Example.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf366},
pmid = {41239971},
issn = {1550-9109},
}
@article {pmid41239762,
year = {2025},
author = {Covre, ER and Laranjeira, C and Carreira, L and Höring, CF and Góes, HLF and Baldissera, VDA and Marques, PG and Meireles, VC and Tostes, MFDP and Oliveira, RR and Paiano, M and Ageno, RS and Moroskoski, M and Alcaraz, JP and Vissoci, JN and Facchini, LA and Salci, MA},
title = {Prevalence and Predictors of Long Covid in a Cohort of Brazilian Adults 12 Months After Acute Infection: A Cross-Sectional Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70467},
pmid = {41239762},
issn = {1369-7625},
support = {//This study was funded by Minist&#xe9;rio da Ci&#xea;ncia, Tecnologia, Inova&#xe7;&#xf5;es e Comunica&#xe7;&#xf5;es (FNDCT/MCTIC), Minist&#xe9;rio da Sa&#xfa;de (MS) and Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)-Processo n&#x25e6; 402882/2020-2. It was also supported by FCT-Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia, I.P. (UID/05704/2023) and by the Scientific Employment Stimulus-Institutional Call-[https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 20 September 2025]./ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Brazil/epidemiology ; *COVID-19/complications/diagnosis/epidemiology ; Cross-Sectional Studies ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; },
abstract = {INTRODUCTION: Since the onset of the pandemic in early 2020, various reports have emerged regarding persistent symptoms associated with Covid-19. Nevertheless, there is insufficient data on the persistence of symptoms over time. This study sought to estimate the prevalence of persistent symptoms 12 months after Covid-19 infection and identify predictors of long Covid in adults living in the State of Paraná, southern Brazil, according to the level of severity of Covid-19 infection.<br><br>METHOD: An observational and cross-sectional survey was conducted with Brazilian adults diagnosed with Covid-19, as assessed from data available in two official Covid-19 notification databases in Brazil, using telephone interviews. Descriptive statistics, tests of associations and simple and multiple binary logistic regression analysis were used to identify predictors of long Covid.<br><br>RESULTS: In total, 1033 adults participated in the study. The overall prevalence of long Covid was 60.3% (n&#x2009;=&#x2009;623). Prevalence was higher in women (67.7%), people aged between 50 and 59 years (65.8%) and in individuals who received treatment in an Intensive Care Unit (ICU) during the acute phase of Covid-19 infection (74.4%, n&#x2009;=&#x2009;241). The risk factors associated with a greater chance of developing long Covid were: female (OR 2.38; 95% CI 1.55; 3.66), living in the Brazilian northwest health macro-region (OR 2.20; 95% CI 1.21; 4.00), presenting multimorbidity (OR 1.86; 95% CI 1.06; 3.28), having an average of six symptoms in the acute phase of Covid-19 (OR 1.22; 95% CI 1.17; 1.28) and having received treatment in an ICU (OR 4.86; 95% CI 2.83; 8.35) and inpatient ward (OR 2.45; 95% CI 1.47; 4.09).<br><br>CONCLUSIONS: The results highlight the high prevalence of long Covid and support the formulation of health policies capable of minimising the consequences on the population, on the services offered by professionals and on health systems.<br><br>The study topic's importance was based on the patients' experiences in the author's previous research and the need to develop patient-centred care.},
}
@article {pmid41239370,
year = {2025},
author = {Lindblom, S and Lindberg, P and Ljunggren, G and Lee, S and Kisiel, MA and Kolosenko, I and Petrovic, P and Sklivanioti Greenfield, M and Wachtler, C and Fedorowski, A and Wheelock, &#xc5;M and Carlsson, AC},
title = {Prevalence of depression, anxiety, fatigue, and headache before and after long COVID onset: a case-control study in the total population of Region Stockholm.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {633},
pmid = {41239370},
issn = {1741-7015},
support = {M23-01339//&#xc5;ke Wiberg Stiftelsen/ ; HLF20210053//The Swedish Heart-lung foundation/ ; 2021-06546//The Swedish Research Council/ ; FoUI-97300//Region Stockholm/ ; },
mesh = {Humans ; Male ; Female ; Sweden/epidemiology ; *COVID-19/epidemiology/psychology/complications ; *Fatigue/epidemiology/etiology ; *Headache/epidemiology/etiology ; Case-Control Studies ; Middle Aged ; *Anxiety/epidemiology ; *Depression/epidemiology ; Prevalence ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection, or long COVID, include diverse symptoms and remain a major concern worldwide. This study investigates the occurrence of depression, anxiety, fatigue, and headache 1 year prior to the COVID-19 pandemic (2019), 12 months prior to, and 6 months after long COVID diagnosis in individuals diagnosed with long COVID and matched population-based controls.<br><br>METHODS: This case-control study included nonhospitalized individuals diagnosed with long COVID compared with controls without long COVID, matched by age, sex, and neighborhood socioeconomic status. Data were collected from the Stockholm Regional Health Care Data Warehouse (VAL), including diagnoses in 2019, 12&#xa0;months before, and 6&#xa0;months after the long COVID diagnosis. Conditional logistic regression was used to calculate odds (OR) ratios and 99% confidence intervals (CI).<br><br>RESULTS: A total of 5589 cases (mean age: 47&#xa0;years, 69% female) and 47,561 controls were included. Individuals with long COVID had a higher pre-pandemic frequency of the following diagnoses: depression (women: OR 1.57 (1.26-1.97), men: OR 1.40 (0.88-2.23)), anxiety (women: OR 1.65 (1.41-1.93), men: OR 2.10 (1.56-2.84)), fatigue syndrome after viral infection (women: OR 1.96 (0.86-4.48), men: OR 2.22 (0.29-17)), and headache (women: OR 2.45 (1.96-3.05), men: OR 2.89 (1.86-4.50)). Individuals with long COVID also had a higher frequency of these diagnoses 12&#xa0;months before and 6&#xa0;months after the long COVID diagnosis was made, regardless of sex.<br><br>CONCLUSIONS: Individuals with long COVID had a higher prevalence of depression, anxiety, fatigue, and headache both before and after being diagnosed with long COVID compared with controls without long COVID. The findings suggest an association between mental health vulnerabilities and long COVID, while the frequency of registered mental health diagnoses remained largely similar after the long COVID diagnosis.},
}
@article {pmid41239121,
year = {2025},
author = {Villasis, NA and Santos, JJ and Ettner, SL and Xu, H and Escarce, JJ and Leung, LB},
title = {Long COVID Disproportionately Reported by Disadvantaged Individuals: A National Survey of U.S. Working-Age Adults.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-09912-w},
pmid = {41239121},
issn = {1525-1497},
support = {RF1 MH133436/MH/NIMH NIH HHS/United States ; 1RF1MH133436-01/MH/NIMH NIH HHS/United States ; IK2 HX002867/HX/HSRD VA/United States ; },
abstract = {BACKGROUND: COVID-19 disproportionately affects racial/ethnic minorities and economically disadvantaged persons, which may also apply to sequelae from acute infection. Little is known about those who live with post-acute sequelae of SARS-CoV-2 infection (PASC), including long COVID, especially those without a formal diagnosis.<br><br>OBJECTIVE: To examine self-reported long COVID symptoms and its associations with individual and state characteristics from a national survey sample of working-age adults.<br><br>DESIGN: Repeated cross-sectional survey analysis.<br><br>PARTICIPANTS: Eighteen- to 64-year-old adults who reported ever having had COVID-19 (n&#x2009;=&#x2009;409,087).<br><br>MAIN MEASURES: We examined long COVID responses from the online Household Pulse Survey (9/22/2022-10/30/2023), administered by the Census Bureau and the National Center for Health Statistics. Long COVID was defined as having "symptoms lasting 3 months or longer that you did not have prior to having coronavirus" (e.g., fatigue, difficulty thinking, shortness of breath) or not. Logistic regression models adjusted for survey week, respondent characteristics (e.g., demographics, acute COVID-19 severity), and state characteristics (e.g., rurality, Health Professional Shortage Areas). We additionally examined concurrent depression and anxiety symptoms.<br><br>KEY RESULTS: The HPS response rate was 6.10% during the study timeframe.[14] Among those who ever had COVID-19, 27.5% reported long COVID symptoms. Among those with long COVID symptoms, 22.6% reported having severe activity limitations. In fully adjusted models, long COVID symptoms were most commonly reported by Hispanic respondents (&#x394;PH&#x2009;=&#x2009;2.3, SE&#x2009;=&#x2009;0.7), among all racial-ethnic groups. Low socioeconomic status was consistently associated with long COVID symptoms: Income (&#x394;P<25k vs >=200k+&#x2009;=&#x2009;11.9, SE&#x2009;=&#x2009;0.9); Medicaid-insurance (&#x394;PMedicaid v Employer-sponsored&#x2009;=&#x2009;02.9, SE&#x2009;=&#x2009;0.5); Uninsurance (&#x394;PUninsured v Employer-sponsored&#x2009;=&#x2009;1.8, SE&#x2009;=&#x2009;0.4). Long COVID symptoms were associated with living in more rural states (&#x394;P&#x2009;=&#x2009;0.08, SE&#x2009;=&#x2009;0.02). Long COVID symptoms were additionally associated with concurrent anxiety (&#x394;PAnx v Not&#x2009;=&#x2009;8.0, SE&#x2009;=&#x2009;0.4) and depressive symptoms (&#x394;PDep v Not&#x2009;=&#x2009;6.7, SE&#x2009;=&#x2009;0.6).<br><br>CONCLUSIONS: Long COVID symptoms and disability were disproportionately reported among survey respondents who were Hispanic and who were economically-disadvantaged. Rural communities were more so impacted.},
}
@article {pmid41238605,
year = {2025},
author = {Toyokura, E and Yamada, K and Asai, K and Tsutsumi, M and Ueda, T and Hirai, K and Furukawa, Y and Miyamoto, A and Nishimura, M and Sato, K and Watanabe, T and Tabuchi, T and Kawaguchi, T},
title = {Dual use of combustible and heated tobacco products associates persistent symptoms with a history of COVID-19: a JASTIS 2023 cross‑sectional study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {38659},
pmid = {41238605},
issn = {2045-2322},
support = {JP23K07631//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *COVID-19/epidemiology ; Middle Aged ; Adult ; SARS-CoV-2 ; *Tobacco Products/adverse effects ; Aged ; Risk Factors ; Dyspnea/etiology/epidemiology ; Cigarette Smoking/adverse effects ; },
abstract = {Multiple reports have identified smoking as a risk factor for long COVID; however, few have distinguished among tobacco product types. We conducted a cross-sectional study using data from an internet-based survey administered in February 2023 to examine the association between 12 persistent symptoms and smoking status in participants with a history of COVID-19. A total of 28,250 participants were included, of whom 5,068 had a history of COVID-19. Among current tobacco users with a history of COVID-19, the odds ratios for persistent symptoms were significantly elevated for four symptoms-arthralgia, chest pain, dyspnea, and dysosmia-compared to never smokers. For subgroup analysis, current tobacco users were categorized into three groups: combustible cigarette (CC), heated tobacco product (HTP), and dual users. Among dual users, the odds ratios were significantly elevated for five symptoms: arthralgia, chest pain, dyspnea, dysgeusia, and dysosmia. CC users showed significantly higher odds for chest pain, dyspnea, and fatigue, while HTP users for dyspnea and sexual dysfunction. Smoking in individuals with a history of COVID-19 associates the prevalence of persistent symptoms, and its impact may vary by smoking type. Separately analyzing smoking subgroups allows for a more accurate understanding of the relationship between persistent symptoms and smoking behavior.},
}
@article {pmid41238390,
year = {2025},
author = {Waters, A},
title = {Long covid: Government failure to recognise disease as occupational is "unconscionable," say unions.},
journal = {BMJ (Clinical research ed.)},
volume = {391},
number = {},
pages = {r2407},
doi = {10.1136/bmj.r2407},
pmid = {41238390},
issn = {1756-1833},
}
@article {pmid41238086,
year = {2026},
author = {Yuan, RL and Wang, SS and Li, PY and Ruan, Y and He, JQ and Zhou, R and Wang, WF and Jiang, YT and Ye, JR and Peng, Y and He, WB and Chu, SF and Zhang, Z and Chen, NH},
title = {SARS-CoV-2 spike protein induces depressive-like behaviors by disrupting astrocytic Cx43-mediated gap junction intercellular communication.},
journal = {Brain, behavior, and immunity},
volume = {131},
number = {},
pages = {106176},
doi = {10.1016/j.bbi.2025.106176},
pmid = {41238086},
issn = {1090-2139},
mesh = {Animals ; *Gap Junctions/metabolism ; *Astrocytes/metabolism ; *Connexin 43/metabolism/genetics ; Mice ; Prefrontal Cortex/metabolism ; Cell Communication/physiology/drug effects ; *Depression/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism ; Mice, Knockout ; *COVID-19/metabolism/psychology ; Male ; SARS-CoV-2/metabolism ; Mice, Inbred C57BL ; Neurons/metabolism ; },
abstract = {BACKGROUND: Long COVID has emerged as a global health concern, with depression being one of its most debilitating and poorly understood manifestations. Despite evidence pointing to the role of neuroinflammation and astrocyte-mediated disruptions in brain function, the mechanistic details remain elusive.<br><br>METHODS: SARS-CoV-2 spike receptor-binding domain (RBD) was microinjected into the medial prefrontal cortex (mPFC) to mimic cerebral infection, and the depressive-like behaviors, functional connectivity, and neuronal excitability were recorded for a 16-day period. Immunofluorescence, RNA sequencing, and ELISA were used to evaluate astrocytic gap junctions and inflammation. Gap junction intercellular communication (GJIC) dysfunction was confirmed by transfer of lucifer yellow (LY), cyclic adenosine monophosphate (cAMP), and cyclic GMP-AMP (cGAMP). We also investigated the role of Cx43 using conditional knockout mice, Gap 27-treated mice, and Cx43-knockdown astrocytes. Astrocytic Cx43 overexpression and celecoxib treatment were tested as a potential therapeutic to rescue Cx43 function.<br><br>RESULTS: Mice microinjected with RBD into the mPFC exhibited significant depressive-like behaviors, decreased neuronal excitability, and disrupted functional connectivity, accompanied by a marked reduction in astrocytic Cx43 expression and impaired GJIC. Functional assays, including Lucifer Yellow, cAMP, and cGAMP transfer, confirmed compromised gap junction activity, which was further associated with enhanced astrocytic type I interferon responses and cGAS-STING pathway activation. Conditional knockout of Cx43 in astrocytes or pharmacological inhibition of GJIC mimicked the depressive-like phenotypes induced by RBD. Importantly, Astrocytic Cx43 overexpression and celecoxib treatment restored GJIC, and effectively alleviated depressive-like behaviors in RBD-injected mice.<br><br>CONCLUSIONS: Astrocytic Cx43-mediated GJIC as a promising therapeutic strategy for managing depression in long COVID.},
}
@article {pmid41237918,
year = {2025},
author = {Aggarwal, A and Chanda, A},
title = {Effects of thoracic spinal manipulation in long COVID patients: A randomised controlled trial.},
journal = {Respiratory medicine},
volume = {250},
number = {},
pages = {108503},
doi = {10.1016/j.rmed.2025.108503},
pmid = {41237918},
issn = {1532-3064},
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/complications/rehabilitation/therapy ; *Manipulation, Spinal/methods ; Adult ; SARS-CoV-2 ; Thoracic Vertebrae/physiopathology ; Young Adult ; Treatment Outcome ; Respiratory Function Tests ; },
abstract = {INTRODUCTION: Long COVID patients manifest dyspnoea, chest heaviness, and symptoms, ascertaining deteriorated lung function. As thoracic spinal manipulation in such patients may lead to spinal misalignment, the chest wall compliance may also get affected. This study aimed to determine the role of thoracic spinal manipulation on pulmonary function, thoracic spine mobility, and chest expansion in patients with Long COVID.<br><br>METHODS: A Randomised Controlled trial was done in Dr. D.Y. Patil College of Physiotherapy, Pune, Maharashtra on 42 individuals who fulfilled the inclusion criteria. They were randomly assigned to two groups using the chit method. The experimental group (Group A), with a mean age of 23.85&#xa0;&#xb1;&#xa0;3.55 years (11 males, 10 females), underwent thoracic spinal manipulation in conjunction with pulmonary rehabilitation five times a week for two weeks. The control group (Group B) with a mean age of 24.9 (&#xb1;5.26) years (9 males, 12 females) underwent pulmonary rehabilitation only. After two weeks, primary outcome measures, including pulmonary function, thoracic spine mobility, and chest expansion, were evaluated. The data were analysed with SPSS version 21 software using the Wilcoxon signed-rank and Mann-Whitney tests for within- and between-groups comparisons.<br><br>RESULTS: The experimental group showed a significant improvement (p&#xa0;<&#xa0;0.05) in pulmonary function and thoracic spine mobility, except for thoracolumbar extension and chest expansion parameters versus control group. Within-group analysis of both groups, yielded significant results for all dependent outcome variables. (p&#xa0;<&#xa0;0.05).<br><br>CONCLUSION: The study supports the role of thoracic spinal manipulation in improving pulmonary function and thoracic spine mobility in patients with Long COVID.},
}
@article {pmid41237491,
year = {2025},
author = {Staggs, H and Furst, A and Mills-Finnerty, C},
title = {Characterizing predictors and chronicity of brain fog in long COVID.},
journal = {Psychiatry research},
volume = {354},
number = {},
pages = {116813},
doi = {10.1016/j.psychres.2025.116813},
pmid = {41237491},
issn = {1872-7123},
mesh = {Humans ; Female ; Male ; *COVID-19/complications/psychology ; Adult ; Middle Aged ; *Fatigue/etiology/physiopathology ; Chronic Disease ; *Cognitive Dysfunction/etiology/physiopathology ; },
abstract = {Long COVID is a chronic illness that persists following COVID-19 infection, with fatigue and brain fog as the most frequent complaints. However, there is no objective case definition for brain fog in long COVID and chronicity of symptoms remains unclear. This study recruited two waves of participants: those with a history of COVID-19, who participated in 2023 (N = 793, age = 38.5 ± 13.2, 44% female, 35.1% long COVID) and a follow up cohort collected in 2024 of participants who qualified as having long COVID at time point 1 (N=119, 61 female, 58 male). Participants completed questionnaires and cognitive tasks from home. We trained a binary classification model for long COVID diagnosis (73% accuracy) and a linear regression model for cognitive complaints (RMS error 5.8). A long COVID diagnosis at timepoint 1 was classified by biopsychosocial variables including stress, social support, and sex (women more likely). Symptom clustering revealed that phenotypes with both mental and physical health symptoms were predictive of brain fog, but not phenotypes with only sleep-related or physical symptoms. Markers of brain fog included slower reading and typing, slower reaction times in cognitive tasks, and changes in information processing speed and thresholds for making choices. Timepoint 2 data showed that the majority (82.4%) of participants did not remit from long COVID . These findings highlight the complex biopsychosocial factors that predict having long COVID with brain fog, and the need for interventions to improve remission rates.},
}
@article {pmid41237093,
year = {2025},
author = {, },
title = {Correction: Coping with stressful life disruptions due to long COVID: A qualitative study.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0336986},
pmid = {41237093},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0329831.].},
}
@article {pmid41235245,
year = {2025},
author = {Chen-Camaño, R and DeAntonio, R and López-Vergès, S},
title = {T-cell exhaustion in COVID-19: what do we know?.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1678149},
pmid = {41235245},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *T-Lymphocytes/immunology ; T-Cell Exhaustion ; },
abstract = {T-cell exhaustion is a terminal state of immune dysfunction characterized by impaired proliferation and effector functions, diminished cytokine secretion, and sustained expression of inhibitory receptors. In coronavirus disease 2019 (COVID-19), increasing evidence links exhausted T-cell phenotypes with poor clinical outcomes, including severe disease, delayed viral clearance, and persistent symptoms associated with Long COVID. Exhaustion results from prolonged antigenic stimulation and inflammatory signals and is marked by transcriptional reprogramming, metabolic and epigenetic dysregulation, and co-expression of inhibitory receptors such as programmed cell death protein-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Notably, exhausted phenotypes in COVID-19 frequently coexist with hyperactivation, raising the unresolved question of whether inhibitory receptor expression reflects transient activation or irreversible dysfunction. Emerging therapeutic strategies to reverse these dysfunctional states include immune checkpoint inhibitors, cytokine modulation, metabolic interventions, and epigenetic therapies, although their clinical translation remains at an early stage. Critical research gaps include the scarcity of longitudinal data, incomplete profiling of T-cell subsets across disease stages during COVID-19 and Long COVID-19, and contradictory evidence of vaccine-induced exhaustion with limited understanding of its consequences. This non-systematic literature review synthesizes current advances in COVID-19 immunopathology and therapeutic strategies, underscoring that understanding T-cell exhaustion is crucial to improving outcomes and shaping next-generation immunotherapies and vaccines.},
}
@article {pmid41235244,
year = {2025},
author = {Wang, D and Zhang, F},
title = {CKD-related impairment in humoral and cellular immune response and potential correlation with long COVID-19: a systematic review.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1690298},
pmid = {41235244},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention &amp; control ; *Immunity, Humoral ; *Renal Insufficiency, Chronic/immunology/therapy ; *Immunity, Cellular ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/blood/immunology ; Vaccination ; },
abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of morbidity and mortality from SARS-CoV-2 infection (COVID-19). However, their immune response to vaccination may vary among individuals. The purpose of this review was to identify characteristics of alterations in humoral and cellular immune responses to the vaccination, and to provide insights into their immune dysfunctions for a better care of acute COVID-19 and prevention of long COVID-19.<br><br>METHODS: PubMed, Embase, Scopus, Web of science and Cochrane Central were systematically searched. Eligible publications included clinical studies reporting immune response to COVID-19 vaccination in CKD patients without dialysis or KT, CKD patients undergoing dialysis, as well as CKD patients with KT. Demographics, measurements and results of their humoral and cellular response were evaluated, and the quality of studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tool and the Newcastle-Ottawa quality assessment scale (NOS).<br><br>RESULTS: A total of 31 eligible studies were identified. A decreased proportion of patients with KT showed anti-S IgG positivity after the 2[nd] (67%) and 3[rd] (56.6%) dose of vaccination. Similarly, a decreased proportion of these patients presented S-specific T-cell response after the 2[nd] (17.7%) and 3[rd] (12.9%) dose. Though lower anti-S IgG titers in patients with CKD or on dialysis, as well as T-cell response in patients on dialysis were reported to be lower after the 2[nd] or 3[rd] dose of vaccination, conflicting results were reported by other studies. Limited studies on correlated change between humoral and cellular immune response revealed a low rate of co-presence of the two in patients with dialysis, though antibody level was correlated with rate of cellular response, while no such correlation was revealed in patients with KT.<br><br>CONCLUSION: The study provides crucial information on features of humoral and cellular immune responses to COVID-19 vaccinations in CKD patients, and suggests possible directions for strategy of management such as antibody monitoring, additional booster dose or immunomodulatory therapies not only for acute COVID-19 but also for long COVID-19.},
}
@article {pmid41232803,
year = {2026},
author = {Brand, O and Kirkham, S and Jagger, C and Ozols, M and Purohit, K and Zhang, Z and Lennon, R and Hussell, T and Eckersley, A},
title = {Lung basement membranes are compositionally and structurally altered following resolution of influenza infection.},
journal = {Mucosal immunology},
volume = {19},
number = {1},
pages = {1599-1612},
doi = {10.1016/j.mucimm.2025.11.005},
pmid = {41232803},
issn = {1935-3456},
mesh = {Animals ; *Basement Membrane/metabolism/pathology/virology/immunology ; *Lung/pathology/metabolism/virology/immunology ; Mice ; *Orthomyxoviridae Infections/immunology/metabolism/pathology/virology ; Laminin/metabolism ; Collagen Type IV/metabolism ; Humans ; Mice, Inbred C57BL ; *Influenza, Human/immunology ; Disease Models, Animal ; Proteomics/methods ; Female ; },
abstract = {Identification of pathways preventing timely recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected, reduction in lung basement membrane proteins 21 days after influenza infection when mice had symptomatically recovered. Basement membrane provides a critical scaffold for heterogeneous cell types and the proteins they secrete/express at the endothelial and epithelial barrier. Further peptide location fingerprinting analysis shows inherent structure-associated changes within core collagen IV and laminin components, particularly within the NC1 domains of collagen IV. Our results imply lingering damage to the basement membrane network despite symptomatic recovery from viral infection. Surprisingly, similar structure-associated changes in laminin and collagen IV components are also observed in non-infected, aged mice indicating that inflammation-driven basement membrane degeneration may contribute to tissue ageing. Interestingly, macrophages in regions deficient in basement membrane express collagen IV and laminin chains. Repair of the basement membrane should therefore be targeted to improve overall lung health. Non-technical summary: Lung virus infection is a constant global threat, despite developments in vaccination and anti-viral treatments. We have a deep understanding of this inflammatory condition but less is known about the drivers of persistent problems, including fatigue and breathlessness as illustrated by "long COVID". Here, we reveal a novel finding that a critical structure in the lung (the basement membrane) remains damaged after the influenza virus and symptoms have cleared. This structure supports a variety of cells and forms a barrier that lines the airspaces. It also regulates fluid and cell movement into these airspaces. Remarkably, we show that similar changes after virus infection are also evident in aged lungs, which implies that lung complications with age may be due to repeated inflammation. By identifying these persistent basement membrane changes, we provide an entirely novel area to target with new medicines to treat complications arising from viral infection.},
}
@article {pmid41232748,
year = {2026},
author = {Alves Costa Silva, C and Pinheiro Bomfim, A and Dutra Medeiros, J and de Jesus Silva, J and Cazé-Ceron, AB and Cerqueira-Silva, T and Khouri, R and Barral, A and Barral-Netto, M and da Rocha Fernandes, G and Gomes Barbosa, C and S Boaventura, V},
title = {Nasal microbiota and clinical features in acute flu-like illness: COVID-19 status and long COVID follow-up.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {162},
number = {},
pages = {108196},
doi = {10.1016/j.ijid.2025.108196},
pmid = {41232748},
issn = {1878-3511},
mesh = {Humans ; *COVID-19/microbiology ; Male ; Female ; Middle Aged ; *Microbiota ; SARS-CoV-2 ; Adult ; Aged ; Follow-Up Studies ; *Nose/microbiology ; Influenza, Human/microbiology ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVES: Long COVID (LC) is a challenging medical condition. Reliable diagnostic and targetable biomarkers of LC for a proper and early diagnosis and clinical care are an unmet medical need. We aimed to evaluate targetable biomarkers for LC management.<br><br>DESIGN: Comparison of nasal microbiota and clinical features in 291 individuals with acute influenzae-like illness (ILI), comparing COVID-19-positive (n=193) and negative (n=98) groups, with further stratification by long COVID (LC) outcomes (persistent symptoms >3 months).<br><br>RESULTS: Clinical characteristics were balanced across groups, with upper respiratory symptoms predominating. Individuals who developed LC exhibited more cardiorespiratory symptoms during acute infection (70% vs 48%, P=0.002). Nasal microbiota analysis revealed lower alpha diversity in COVID-19-positive individuals vs other ILI (Wilcoxon: Chao2 index P=0.03305; Shannon diversity index P=0.02578; Simpson diversity index P=0.1082) but no differences in beta diversity or taxonomic composition between groups, including LC vs recovered individuals. EBV/CMV infection/reactivation was not associated with LC. Sensitivity analyses confirmed robustness to methodological and temporal biases.<br><br>CONCLUSIONS: Findings suggest acute nasal microbiota disruption in individuals with COVID-19, but no LC-specific microbial profile.},
}
@article {pmid41232201,
year = {2025},
author = {Nunes, M and Kruger, A and Fielding, B and Kell, DB and Pretorius, E},
title = {The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters.},
journal = {Thrombosis research},
volume = {256},
number = {},
pages = {109530},
doi = {10.1016/j.thromres.2025.109530},
pmid = {41232201},
issn = {1879-2472},
mesh = {Humans ; *Fibrin/metabolism ; *Blood Coagulation ; *Thrombin/metabolism ; Fibrinogen/metabolism ; *COVID-19/blood ; Fibrinolysis ; *Diabetes Mellitus, Type 2/blood ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Blood Coagulation Factors ; },
abstract = {Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor-depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.},
}
@article {pmid41231196,
year = {2025},
author = {O'Connor, DB and Greenwood, DC and Mansoubi, M and Bakerly, ND and Bhatia, A and Collett, J and Davies, HE and Dawes, J and Delaney, BC and Ezekiel, L and Leveridge, P and Mir, G and Muehlhausen, W and Rayner, C and Scott, JT and Sivan, M and Tucker-Bell, I and Vashisht, H and Ward, T and Winch, D and Dawes, H and , },
title = {Daily stress and worry are additional triggers of symptom fluctuations in individuals living with Long COVID: results from an intensive longitudinal cohort study.},
journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine},
volume = {59},
number = {1},
pages = {},
pmid = {41231196},
issn = {1532-4796},
support = {//National Institute for Health and Care Research/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/psychology/complications/physiopathology ; *Stress, Psychological/psychology/complications ; Middle Aged ; Longitudinal Studies ; *Anxiety/psychology ; Aged ; Fatigue/psychology ; Adult ; *Depression/psychology ; *Rumination, Cognitive/physiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; United Kingdom ; Dizziness ; SARS-CoV-2 ; *Symptom Flare Up ; },
abstract = {BACKGROUND: Recent research has shown that exertion in physical, cognitive, social, and self-care activities triggers symptom severity in individuals with Long COVID.<br><br>PURPOSE: The current study aimed to investigate whether daily emotional exertions (stress, worry, rumination) were associated with symptom exacerbation, over and above influences of effortful daily activities, in individuals with Long COVID.<br><br>METHODS: In total, 376 participants were recruited from UK Long COVID clinics and community settings and completed daily assessments of activity and severity of 8 core symptoms every 3&#x2009;hours for up to 24&#x2009;days; 155 participants completed daily assessments of stress, worry, and rumination for at least 7 consecutive days.<br><br>RESULTS: Days with higher stress scores were associated with increased severity of all symptoms on the same day, after adjusting for activities, demographic and medical factors (P-values &#x2264; .007). Days with higher stress scores also predicted more severe anxiety and depression symptoms 1 day later (P&#x2009;<&#x2009;.001) and more severe anxiety (P&#x2009;<&#x2009;.001) and dizziness symptoms (P&#x2009;=&#x2009;.003) 2 days later. Days with higher worry scores were associated with increased fatigue (P&#x2009;<&#x2009;.001), anxiety (P&#x2009;<&#x2009;.001), depression (P&#x2009;<&#x2009;.001), and cognitive dysfunction (P&#x2009;=&#x2009;.002) on the same day, but decreased anxiety (P&#x2009;=&#x2009;.003) and depression (P&#x2009;=&#x2009;.002) symptoms 1 day later and less severe pain (P&#x2009;=&#x2009;.002) symptoms 2 days later. Daily rumination was only associated with 2 symptoms.<br><br>CONCLUSIONS: Daily stress and worry are distinct factors linked to fluctuations in same-day and next-day Long COVID symptoms, with daily stress showing the strongest association-consistent with patterns of postexertional symptom exacerbation. These findings highlight the importance of considering stress and worry as potential therapeutic targets and integrating their management into self-care programs.},
}
@article {pmid41231115,
year = {2025},
author = {Rai, KK and Gowman, H and Harrison, CS and Gruben, DC and Butfield, R and Hulme, R and Volkman, HR and Nguyen, JL and Yang, J},
title = {Understanding the role of COVID-19 vaccination in all-cause healthcare resource utilisation among adults with long COVID in the UK primary care setting: data from the 2022-2023 respiratory virus season.},
journal = {Expert review of vaccines},
volume = {24},
number = {1},
pages = {1047-1058},
doi = {10.1080/14760584.2025.2589215},
pmid = {41231115},
issn = {1744-8395},
mesh = {Humans ; United Kingdom/epidemiology ; *COVID-19/prevention &amp; control/epidemiology/economics ; *Primary Health Care/statistics &amp; numerical data/economics ; Adult ; Female ; Male ; Middle Aged ; Retrospective Studies ; *COVID-19 Vaccines/administration &amp; dosage ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Aged ; *Vaccination/statistics &amp; numerical data ; Young Adult ; SARS-CoV-2/immunology ; Adolescent ; },
abstract = {BACKGROUND: The role COVID-19 vaccination on healthcare resource utilization (HCRU) and cost remains unclear, especially during Omicron predominance and among high risk UK populations.<br><br>RESEARCH DESIGN AND METHODS: A retrospective cohort study using UK The Health Improvement Network (THIN) primary care data included adults (&#x2265;18&#x2009;years) with confirmed or suspected COVID-19 between September 2022 and May 2023. Three cohorts were defined: Highest risk (eligible for two seasonal doses), High Risk (eligible for one dose), and All COVID-19 patients. Long COVID was identified as&#x2009;&#x2265;1 symptom or diagnostic/referral code, &#x2265;4&#x2009;weeks post COVID-19 diagnosis. Inverse probability of treatment weighting assessed associations between vaccination status (yes/no and time since vaccination) and long COVID, HCRU, and costs.<br><br>RESULTS: In both Risk Cohorts, COVID-19 vaccination was not associated with long COVID incidence. However, in the High Risk (n&#x2009;=&#x2009;1,889) and All Patients cohorts (n&#x2009;=&#x2009;8,507) outpatient specialist referrals were significantly lower in the 3-6-month post-vaccination group versus&#x2009;>&#x2009;6&#x2009;months (rate ratio: 0.28; 95% CI: 0.10-0.79, p&#x2009;<&#x2009;0.05 and 0.46; 95% CI: 0.27-0.79; p&#x2009;&#x2264;&#x2009;0.01, respectively).<br><br>CONCLUSIONS: COVID-19 vaccination was not consistently associated with incidence of long COVID or all-cause HCRU. Findings suggest potential subgroup-specific benefits, highlighting the importance of annual vaccination. Further research with larger sample size and longer-term follow-up is warranted.},
}
@article {pmid41230640,
year = {2025},
author = {Sargeant, S and Wilkinson, S and Lorraway, M and McDonald, S},
title = {Contested illness and communication: Positioning long Covid in online discussion forums.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053251389517},
doi = {10.1177/13591053251389517},
pmid = {41230640},
issn = {1461-7277},
abstract = {The World Health Organization (WHO) officially acknowledged long COVID as a post COVID-19 condition in 2021. Emerging research shows that long COVID may be considered a contested illness due to unknown causal mechanisms, diagnostic uncertainty, poor recovery/treatment outcomes and people reporting illness dismissal experiences when seeking healthcare. Informed by the sick role and positioning theories, this study explored people's experiences of seeking healthcare for long COVID by examining posts in two online forums (Mayo Clinic Connect and Reddit, from June and July 2023). Template analysis helped to identify12 forum threads containing a total of 305 posts. Inductive thematic analysis of posts identified three themes: (a) 'The concept of time', (b) 'The importance of symptom legitimacy', and (c) 'Responding to diagnostic dismissal'. Healthcare professionals are critical in validating the patient experience without a formal long COVID diagnosis, and in supporting long COVID recovery needs by acknowledging heterogeneity and diagnostic difficulties.},
}
@article {pmid41228073,
year = {2025},
author = {Cianciulli, A and Santoro, E and Manente, R and Pacifico, A and Barberio, I and Satriani, V and Boccia, G},
title = {Clinical and Symptom Profiles of Long-COVID Patients in Italy: A Cross-Sectional Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {41228073},
issn = {2227-9032},
abstract = {Background/Objectives: Long COVID is a multisystemic condition persisting beyond the acute phase of SARS-CoV-2 infection. Data on young, community-dwelling adults in Italy remain limited. To describe the sociodemographic, clinical, and symptom profiles of Long-COVID patients in an Italian cohort. Methods: Cross-sectional survey (February-April 2025) on 250 adults with prior COVID-19. A validated 24-item questionnaire was administered. Descriptive statistics, 95% confidence intervals (CIs), Hedges' g effect sizes, and exploratory subgroup analyses (sex, age ≤ 30 vs. >30) were performed. Results: Participants were 63.6% female, 56% ≤ 30 years, 4.4% with comorbidities. Acute symptoms included muscle/joint pain (2.79 ± 1.31), weakness (2.77 ± 1.28), and tiredness (2.76 ± 1.31). Persistent symptoms were excessive tiredness (2.36 ± 1.27), weakness (2.25 ± 1.29), and muscle/joint pain (2.25 ± 1.25). Acute → persistent changes were significant (p < 0.01, paired t-test) with effect sizes g = 0.31-0.42. Women reported higher persistent fatigue (mean diff = 0.40, 95% CI 0.01-0.78, p = 0.04). Conclusions: Even among young adults without comorbidities, Long COVID imposes a relevant burden. Findings highlight the need for multidisciplinary pathways, nursing-led follow-up, and targeted self-management education.},
}
@article {pmid41228071,
year = {2025},
author = {Neba, R and Pedaprolu, LS and Neba, B and Sambamoorthi, U},
title = {Long COVID Is Associated with Excess Direct Healthcare Expenditures Among Adults in the United States.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {41228071},
issn = {2227-9032},
abstract = {Background: Long COVID can lead to a considerable economic burden because of ongoing care for persistent symptoms such as fatigue, dyspnea, or cognitive dysfunction. However, systematic research quantifying healthcare expenditures associated with long COVID remains limited. Objective: This study estimated the excess total, payer, and out-of-pocket healthcare expenditures associated with long COVID among adults in the United States (US). Methods: This was a cross-sectional analysis on adults ≥18 years using 2022 Medical Expenditure Panel Survey (MEPS) data (N = 17,119; representing approximately 254 million adults). Economic burden was measured with (1) total, (2) payer, and (3) out-of-pocket expenditures by individuals and their families. Generalized linear models (GLMs) with gamma distribution and log link were utilized to estimate excess expenditures associated with long COVID after adjusting for age, sex, race and ethnicity, social determinants of health, health status, and lifestyle factors. Results: Overall, 7.0% of the population reported long COVID. Adults with long COVID exhibited higher total (USD 11,305 vs. USD 7162) and payer (USD 9983 vs. USD 6097) expenditures compared to those with no COVID. In a fully adjusted analysis, long COVID was associated with an excess of USD 4098 in total healthcare expenditures and USD 3705 in payer expenditures. We did not observe significant differences in out-of-pocket expenditures between those with long COVID and no COVID. Conclusions: Adults with long COVID had 1.5 times higher total healthcare costs compared to those without COVID. This study highlights the need for comprehensive strategies and policies to reduce the economic burden associated with long COVID.},
}
@article {pmid41227273,
year = {2025},
author = {Emmanouil, M and Georgakopoulou, VE and Drougkas, K and Lembessis, P and Skarlis, C and Gkoufa, A and Sipsas, NV and Mavragani, CP},
title = {Type I Interferon-Related Gene Expression and Laboratory Abnormalities in Acute Infection Are Associated with Long COVID Symptom Burden.},
journal = {Journal of clinical medicine},
volume = {14},
number = {21},
pages = {},
pmid = {41227273},
issn = {2077-0383},
abstract = {Background: Long COVID-defined as the persistence of symptoms or the development of new symptoms beyond four weeks after acute SARS-CoV-2 infection-affects an estimated 10-30% of individuals recovering from COVID-19, posing a significant public health burden. Emerging evidence suggests that type I interferons (IFNs) (a critical group of cytokines in the antiviral defense) and hematologic alterations, such as lymphopenia and elevated inflammatory markers, are linked to both the severity of acute COVID-19 and the likelihood of developing long-term symptoms. The aim of this study is to explore the association between type I IFN signatures and long COVID. A second aim is to examine the relationship between laboratory findings during acute infection and long COVID. Methods: The study included 61 patients investigated for the presence of long COVID symptoms 16.5 ±1.5 months after acute infection. Patients were divided into two groups of higher symptom burden of long COVID and those with milder symptoms based on demographic, laboratory, and clinical data as well as type I IFN-inducible gene expression (MX-1, IFIT-1, and IFI-44) measured in peripheral blood by real-time PCR. Data collected during acute infection were recorded. Peripheral blood samples were collected during the acute phase of infection, within the first 48 h of hospital admission. IFN-inducible gene expression was measured prospectively at that time, and RNA was extracted immediately for subsequent analysis. Results: History of intubation emerged as a significant associated factor of severe long COVID, with 75% of intubated patients reporting >8 persistent symptoms approximately 16 months post-infection. Higher white blood cell (WBC) and neutrophil counts but lower eosinophil and monocyte counts in acute infection were found to be associated with a high burden of long COVID symptoms. Interestingly, absolute monocyte count was found to independently correlate with higher long COVID symptom burden. Lactate dehydrogenase (LDH) and serum glutamic-oxaloacetic transaminase (SGOT) also differed significantly between groups, with higher levels correlating with a high burden of long COVID symptoms. Notably, MX-1 transcript levels in peripheral blood at the time of acute infection were reduced in patients with a high burden of long COVID symptoms, suggesting that dysregulated immune responses during the acute phase may contribute to persistent symptoms. Conclusions: These findings suggest the potential association of hematological and immune markers with long COVID severity, as well as the importance of monitoring these parameters to identify at-risk patients for early interventions.},
}
@article {pmid41227265,
year = {2025},
author = {Adeyemi, C and Breuer, L and Kodvawala, R and Miller, D and Powers-Fletcher, MV},
title = {A Cohort Study Characterizing the Outcomes Following an Acute SARS-CoV-2 Infection in Pregnancy.},
journal = {Journal of clinical medicine},
volume = {14},
number = {21},
pages = {},
pmid = {41227265},
issn = {2077-0383},
abstract = {Background/Objectives: Current estimates suggest that 6% of COVID-19 survivors develop a post-viral sequela known as Long COVID. Among those at risk for this sequela, pregnant individuals are a vulnerable patient population, but they are understudied as to the nature of their symptomology and potential adverse outcomes. Methods: This retrospective study evaluated a cohort of 150 pregnant individuals with a history of acute SARS-CoV-2 infection during pregnancy, observing for Long COVID symptoms and assessing for adverse outcomes. Of this cohort, 64% identified as Black and/or Latina, which provides a more diverse representation compared to previously published studies. Results: Within this cohort, 26.7% of individuals experienced at least one symptom of Long COVID; subcohorts, which were categorized based on presence or absence of Long COVID symptomology, presented with varying phenotypes. Pain, mental health dysfunction or psychological problems, and fatigue were the predominant symptoms documented for patients who averaged two Long COVID symptoms after at least 30 days following a COVID-19 diagnosis. Different adverse outcomes were higher in frequency among subcohorts, highlighting a need for continued study to explore the nuances of the impact of COVID-19 on this unique and vulnerable population. The most notable trends between subcohorts related to treatment patterns for acute COVID-19, vaccine status, and cesarean delivery rates. Conclusions: By providing a description of the documented health experience for a predominantly non-White cohort of individuals who were diagnosed with an acute SARS-CoV-2 during pregnancy, our study contributes to a foundation upon which future studies can build.},
}
@article {pmid41226731,
year = {2025},
author = {Varghese, S and Al-Hassani, I and Al-Aani, U and Rob, NJ and Al-Mannai, S and Jaguri, A and Yousif, RA and Al-Mulla, A and Palayangal, FF and Laws, S and Al-Ali, D and Zakaria, D},
title = {Long-Term Complications of Multisystem Inflammatory Syndrome in Children and Adults Post-COVID-19: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226731},
issn = {1422-0067},
mesh = {Adult ; Child ; Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Systemic Inflammatory Response Syndrome/complications/therapy/etiology ; },
abstract = {The SARS-CoV-2 pandemic has posed global medical challenges due to its ability to affect multiple organ systems. Among the post-COVID-19 complications, multisystem inflammatory syndrome has emerged as a severe condition affecting both children (MIS-C) and adults (MIS-A). This review aims to compile and analyze published data to investigate clinical characteristics, laboratory findings, and outcomes of MIS post-COVID-19. A comprehensive search of various databases was conducted to identify studies reporting MIS-related complications in pediatric and adult populations post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 64 studies met our inclusion criteria, and compiled results revealed that cardiac complications were the predominant manifestation followed by gastrointestinal, hematologic, neurological, and mucocutaneous involvement. Laboratory findings consistently demonstrated elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6. Most patients required hospitalization, and many needed intensive care; treatment typically involved IVIG, corticosteroids, and biologic therapies. While most patients recovered, a subset experienced persistent complications. These findings highlight the importance of early recognition, multidisciplinary management, and structured follow-up for MIS. Future research is warranted to clarify the underlying mechanisms, risk factors, and long-term outcomes associated with MIS in post-COVID-19 patients.},
}
@article {pmid41226453,
year = {2025},
author = {Cimini, E and Vergori, A and Cimaglia, C and Tartaglia, E and Notari, S and Colavita, F and Matusali, G and Mastrorosa, I and Mazzotta, V and Chinello, P and Mencarini, P and Giancola, ML and Abdeddaim, A and Casetti, R and Grassi, G and Gili, S and Cristofanelli, F and Maggi, F and Piselli, P and Girardi, E and Antinori, A and Camici, M},
title = {Inflammatory Milieu and Specific T-Cell Response Observed Three Months and One Year After SARS-CoV-2 Infection in Long COVID Subjects.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226453},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/blood/pathology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Aged ; *T-Lymphocytes/immunology ; *Inflammation/immunology/blood ; Adult ; Intercellular Adhesion Molecule-1/blood ; Biomarkers/blood ; Cytokines/blood ; Interleukin-6/blood ; },
abstract = {Long COVID (LC) is characterized by a wide range of symptoms, the causes of which remain unclear. We investigated associations between inflammatory and coagulation factors, adaptive immune response to SARS-CoV-2, and LC. We enrolled 196 unvaccinated individuals with SARS-CoV-2 (March-June 2020). Blood samples were collected at three (T3M) and twelve (T12M) months post infection. Plasma concentrations of coagulation factors (D-Dimer, E-Selectin, ICAM-1, VCAM-1) and inflammatory markers (IL-6, IL-8, TNF-α, IL-1β) were measured by ELISA, and SARS-CoV-2-specific T-cell response was assessed by Elispot. LC occurred in 66/196 patients (34%); 77.8% had been hospitalized. Respiratory symptoms were present in 54%, fatigue in 30%, and neuropsychological symptoms in 14%. At T3M, hospitalized patients exhibited higher levels of ICAM-1, VCAM-1, and IL-6, along with increased immunoreactivity. LC patients exhibited elevated IL-8 and TNF-α and enhanced immunoreactivity at T3M, though these differences were not observed at T12M. Inflammatory and coagulation markers were altered at three months after acute infection, with some changes persisting at one year, suggesting a long-term immunological impact of SARS-CoV-2 on the inflammatory response. A SARS-CoV-2-specific T-cell response was still detectable at T12M, albeit at a lower level than at T3M, suggesting the persistence of protective memory T-cells beyond the acute phase.},
}
@article {pmid41226417,
year = {2025},
author = {Charles, AL and Debrut, L and Oulehri, W and Vincent, V and Delagreverie, H and Asael, P and Riou, M and Giannini, M and Meyer, A and Geny, B},
title = {Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226417},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/mortality/metabolism/pathology ; *Leukocytes, Mononuclear/metabolism ; Female ; Male ; *Mitochondria/metabolism ; Middle Aged ; Severity of Illness Index ; Aged ; SARS-CoV-2 ; Oxygen Consumption ; Cell Respiration ; Adult ; },
abstract = {COVID-19 is a public health issue with a significant mortality rate and potential long-lasting disabling symptoms responsible for the long-COVID syndrome. Mitochondrial dysfunction is a key mechanism but whether peripheral blood mononuclear cell (PBMC) mitochondrial respiration changes might be associated with mortality and/or occurrence and severity of long-COVID syndrome remains to be investigated. We determined mitochondrial respiratory chain oxygen consumption in twenty COVID-19 patients hospitalized in the intensive care unit and analyzed their remaining symptoms at the third year after hospital release. PBMC mitochondrial respiration was decreased in COVID-19 patients compared to the control group (14.13 ± 2.35 vs. 6.21 ± 0.88 pmol/s/10[6] cell, p = 0.0006 for the OXPHOS state by CII). Considering COVID severity, such a decrease was greater in long-COVID patients and in patients who deceased (4.91 ± 0.75, p = 0.008 and 4.94 ± 1.11 pmol/s/10[6] cell, p = 0.04, respectively). PBMC markers of inflammation also increased with the severity of COVID (1.0 ± 0.08 vs. 14.45 ± 2.07, p = 0.02 for ISG15 in patients who died) and ISG15 negatively correlated with PBMC mitochondrial respiration (r = -0.67, p = 0.02 for CII). In conclusion, this study shows that the greater the impairment in PBMC mitochondrial respiration in patients hospitalized in the intensive care unit for COVID-19, the greater the mortality rate and the more severe the long-COVID symptoms-three years after hospital discharge. Further, PBMC markers of inflammation also increased with the severity of COVID and ISG15 negatively correlated with PBMC mitochondrial respiration. These results support that PBMC mitochondrial respiration might be a biomarker of COVID severity and further studies investigating whether modulation of PBMC mitochondrial respiration might improve COVID-19 patients' prognosis.},
}
@article {pmid41226415,
year = {2025},
author = {Zolotarenko, AD and Poghosyan, HM and Sheptiy, VV and Bruskin, SA},
title = {COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226415},
issn = {1422-0067},
support = {123120500032-9//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Humans ; *COVID-19/genetics/virology/immunology/pathology ; *SARS-CoV-2/physiology ; *Epigenesis, Genetic ; *Epigenome ; Biomarkers/metabolism ; Immunity, Innate ; *Host-Pathogen Interactions/genetics ; MicroRNAs/genetics ; DNA Methylation ; },
abstract = {The epigenetics of COVID-19 is a rapidly expanding field that reveals how the SARS-CoV-2 virus initiates alterations in the host's genome, influencing the susceptibility to infection, the disease severity, and long-term consequences, known as "long COVID." In this review, we describe the mechanisms utilized by the virus to manipulate the host epigenome, suppressing antiviral responses and creating a favorable environment for viral replication. We also highlight virus-induced epigenetic changes across diverse cell populations that contribute to COVID-19 pathogenesis. Notably, the virus reprograms hematopoietic stem and progenitor cells, leading to long-lasting alterations in innate immunity, a phenomenon known as "trained immunity." These epigenetic modifications are maintained in differentiated daughter cells and may explain the persistent inflammation and other symptoms of long COVID. Furthermore, we discuss emerging epigenetic biomarkers of disease severity, including methylation signatures in genes such as AIM2, HLA-C, and PARP9, as well as dysregulated miRNA profiles. Understanding this complex interplay between the virus and the host's epigenetic landscape is crucial for developing new therapeutic approaches that target specific epigenetic modifications to suppress pathological processes and improve clinical outcomes for COVID-19 patients.},
}
@article {pmid41223978,
year = {2026},
author = {Spanoghe, M and Antonacci, T and Schneider, N and Molmans, THJ},
title = {Viewpoint | linking long Covid and AD(H)D through neuroimmune dysfunction: A translational framework proposal for precision medicine.},
journal = {Brain, behavior, and immunity},
volume = {131},
number = {},
pages = {106181},
doi = {10.1016/j.bbi.2025.106181},
pmid = {41223978},
issn = {1090-2139},
}
@article {pmid41223398,
year = {2025},
author = {Canarslan-Demir, K and Ozgok-Kangal, K and Artan, E and Turgut, B},
title = {Does Covid-19 Cause Avascular Necrosis?.},
journal = {Undersea &amp; hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc},
volume = {52},
number = {3},
pages = {361-368},
pmid = {41223398},
issn = {1066-2936},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Retrospective Studies ; Male ; Female ; Middle Aged ; Risk Factors ; Adult ; *Femur Head Necrosis/etiology/epidemiology ; Hyperbaric Oxygenation ; Incidence ; *Osteonecrosis/etiology/epidemiology ; Aged ; },
abstract = {COVID-19 has been associated with an increased risk of avascular necrosis (AVN), which affects various joints, including the hip, vertebrae, knee, and jaw. Understanding AVN's pathogenesis and risk factors as a consequence of COVID-19 is essential for improving treatment and identifying preventive measures. This retrospective cohort study aims to assess the impact of COVID-19 on the etiology of AVN and raise awareness among clinicians. The study analyzed patients diagnosed with AVN and treated with Hyperbaric Oxygen Therapy at Gülhane Training and Research Hospital from January 2018 to January 2023. Patients were categorized into two groups: those admitted before the pandemic (the control group) and those admitted after (the study group). The results showed a significant increase in AVN cases during the post-pandemic period, with a higher incidence of femoral head involvement and more advanced stages of AVN in patients with a history of COVID-19. The findings suggest that COVID-19 and high-dose steroid use may increase AVN risk, highlighting the need for careful steroid management and monitoring for joint pain in these patients. Further research is recommended to explore the link between COVID-19 and AVN, the duration of symptoms, and the prognostic implications.},
}
@article {pmid41223394,
year = {2025},
author = {Zamora, FV and Santos, ACFF and Zamora, AV and Galvao, LKCS and Pimenta, NDS and Salles, JPCEA and Carneiro, VB and Starling, CEF},
title = {Hyperbaric Oxygen Treatment for Long-COVID syndrome: A Systematic Review of Current Evidence on Cognitive Decline.},
journal = {Undersea &amp; hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc},
volume = {52},
number = {3},
pages = {327-335},
pmid = {41223394},
issn = {1066-2936},
mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *Cognitive Dysfunction/therapy/etiology ; *COVID-19/complications ; Executive Function ; Post-Acute COVID-19 Syndrome ; Attention ; Randomized Controlled Trials as Topic ; Fatigue/therapy ; },
abstract = {INTRODUCTION: There is no established specific treatment for long-COVID syndrome (LCS), yet hyperbaric oxygen (HBO2) treatment has been studied as a potential option. Therefore, we conducted a systematic review to evaluate the benefits of HBO2 treatment in LCS patients.<br><br>METHODS: We systematically searched PubMed, Embase, and Cochrane databases until April 2024. Risk of bias and GRADE quality assessment were evaluated. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42024530421.<br><br>RESULTS: Seven studies from seven countries, divided into RCTs and observational studies, included 199 participants. HBO&#x2082; treatment protocols included breathing 100% oxygen at 2.0 ATA until 2.5 ATA; the number of sessions varied from ten to 60 depending on the patient's comorbidities and symptoms. Memory, executive function, attention, fatigue, and pain level improved with HBO2 treatment. The intervention had minimal side effects, and none were serious.<br><br>CONCLUSION: HBO&#x2082; treatment might be a potential option and safe treatment in LCS patients. However, further research should be focused on evaluating its efficacy in a larger number of patients through randomized studies.},
}
@article {pmid41218870,
year = {2025},
author = {He, XY and Li, XH and Tong, ZH},
title = {[Cognitive impairment in long COVID: advances in pathological mechanisms and exercise rehabilitation interventions].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {11},
pages = {1087-1095},
doi = {10.3760/cma.j.cn112147-20250610-00315},
pmid = {41218870},
issn = {1001-0939},
support = {2023YFC0872500//National Key Research and Development Program/ ; Ggyfz202503//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; },
mesh = {Humans ; *Cognitive Dysfunction/rehabilitation/etiology ; *COVID-19/complications/psychology ; *Exercise Therapy ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {Since the outbreak of the novel coronavirus (COVID-19) pandemic, long-term effects of the virus, known as long-COVID, has emerged. It is a chronic syndrome following infection. It is estimated that around 20% of COVID-19 survivors worldwide experience cognitive dysfunction. This is characterized by impairments in executive function, attention, memory, and other cognitive domains, and can have a significant impact on quality of life and social functioning. This article systematically reviewed recent studies and summarized the potential pathological mechanisms underlying cognitive dysfunction in long COVID, including neuroinflammation, glial cell dysregulation, involvement of the olfactory pathway and limbic system, autoimmunity and viral reactivation, cerebrovascular and blood-brain barrier damage, as well as abnormalities in neurotrophic factors and synaptic plasticity. Additionally, it explored the effects of exercise rehabilitation and multidimensional comprehensive rehabilitation strategies. The aim was to provide theoretical and scientific foundations for optimizing intervention programs for cognitive dysfunction in long COVID and for formulating clinical guidelines and public health policies.},
}
@article {pmid41218624,
year = {2025},
author = {Gloeckl, R and Rischer, R and Schneeberger, T and Jarosch, I and Blome, C and Koczulla, R},
title = {[Healthcare Situation of 3,345 Long COVID Patients in Germany: Results of a Nationwide Survey].},
journal = {Pneumologie (Stuttgart, Germany)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2725-5650},
pmid = {41218624},
issn = {1438-8790},
abstract = {Long COVID includes persistent symptoms after SARS CoV 2 infection and leads to multiple physical and psychosocial burdens.Between March and April 2025, a nationwide sample of long COVID patients was recruited by means of an anonymous online survey. Demographic parameters, symptoms, use of outpatient/inpatient care services and subjective satisfaction with care were recorded.In total, 3345 people (average age 49 ± 13 years; 81.5% women) completed the survey. 83.8% reported a medically confirmed long COVID diagnosis, with a further 12.2% reporting a post-vac syndrome. The average duration of symptoms was 2.8 ± 1.1 years, with only 36.4% reporting an improvement in their symptoms over time. Almost nine out of ten patients (89.1%) were on long-term sick leave (average 1.8 ± 1.3 years), 70.8% reported total or partial incapacity for work and 46.4% applied for a pension. General practitioner care was the first point of contact for 75.7%. Over the course of the illness, 93% consulted more than three and 21.5% more than ten different doctors. Personal financial contributions were high: 41.4% invested more than € 1,000 and 11.3% more than € 10,000 in diagnostics or therapy. 60% received a rehabilitation intervention. Overall, 97.2% rated their care as "poor" or "very poor".This survey highlights a high and persistent burden among long COVID patients, as well as significant socioeconomic consequences, accompanied by a predominantly negative evaluation of the current care situation. Improvements require structured, easily accessible, and cross-sectoral services. Improving the primary care system, establishing clear referral pathways, and (where clinically indicated) integrating rehabilitative interventions into an interdisciplinary care concept could help to improve the care situation of patients with long COVID.},
}
@article {pmid41218055,
year = {2025},
author = {Panda, R and Mukherjee, R and Singh, K and Lahoti, S and Rai, AK and Verma, A and Bhalla, S and Chandwani, H and Rai, K and Mohapatra, A},
title = {Effects of the ECHO tele-mentoring program on Long COVID management in health facilities in India: A mixed-methods evaluation.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0331293},
pmid = {41218055},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/therapy/epidemiology ; India/epidemiology ; Female ; Male ; Telemedicine ; Middle Aged ; Adult ; SARS-CoV-2/isolation &amp; purification ; *Mentoring/methods ; Health Facilities ; },
abstract = {BACKGROUND: Long COVID emerged as a significant long-term consequence of COVID-19 characterized by persistent symptoms post-infection. ECHO India initiated a training program across four states to enhance the capacity of medical officers (MOs) to manage long COVID syndrome. This study was undertaken to evaluate the effect of the ECHO tele-mentoring program on long COVID management in public health facilities in terms of change in knowledge, competence, and performance of the trained MOs.<br><br>METHODS: Mixed-methods approaches were adopted. Moore's Expanded Outcomes Framework was used for the study. Differences between the pre- and post-interventions were used to populate levels 1-5 of the framework with the trained MOs. This was supplemented by key informant interviews with stakeholders, i.e., trained MOs, hub leaders, and trainers. Level 6 was evaluated with patients seeking services for long COVID from the trained MOs. through quantitative exit interviews and in-depth interviews in two intervention states.<br><br>RESULTS: The pre-post analyses were conducted on a sample size of 204 MOs; a total of 420 beneficiary patients were surveyed. In-depth interviews were done with another 20 patients to measure satisfaction. The findings reveal a significant increase in the MOs' knowledge, learning, and competence. MOs expressed appreciation for the interactive nature of the tele-mentoring sessions and reported increased confidence in dealing with long COVID cases. The training improved the MOs' focus on mental health as a treatment strategy for long COVID. Patients interviewed expressed satisfaction with the care provided by the MOs, in particular with communication skills and the comprehensive approach adopted for long COVID management. They valued the information, the thorough examinations, and the recommendations given by the trained MOs.<br><br>CONCLUSION: The ECHO tele-mentoring program improved the knowledge and skills of primary care medical officers and also resulted in patient satisfaction.},
}
@article {pmid41213692,
year = {2025},
author = {Billias, N and Pouliopoulou, DV and Lawson, A and D'Alessandro, V and Bryant, DM and Peters, S and Rushton, AB and Miller, E and Brunton, L and McGuire, S and Nicholson, M and Birmingham, TB and MacDermid, JC and Quinn, KL and Razak, F and Goulding, S and Galiatsatos, P and Saunders, E and Marsh, J and Pereira, TV and Bobos, P},
title = {Pursuing Reduction in Fatigue After COVID-19 via Exercise and Rehabilitation (PREFACER): a protocol for a randomised feasibility trial.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e102112},
pmid = {41213692},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/complications/rehabilitation ; *Fatigue/etiology/rehabilitation ; Feasibility Studies ; SARS-CoV-2 ; *Exercise Therapy/methods ; Randomized Controlled Trials as Topic ; Female ; },
abstract = {INTRODUCTION: Over 777 million COVID-19 infections have occurred globally, with data suggesting that 10%-20% of those infected develop Long COVID. Fatigue is one of the most common and disabling symptoms of Long COVID. We aim to assess the feasibility and safety of a new, remotely delivered, multimodal rehabilitation intervention, paced to prevent post-exertional malaise (PEM), to support the conduct of a future, definitive randomised trial.<br><br>METHODS AND ANALYSIS: We will conduct a randomised, two-arm feasibility trial (COVIDEx intervention vs usual care). Sixty participants with Long COVID will be recruited and randomised prior to giving informed consent under a modified Zelen design using 1:1 allocation with random permuted blocks via central randomisation to receive either the COVIDEx intervention or usual care. The 50-minute, remotely delivered, COVIDEx intervention will occur twice weekly for 8&#x2009;weeks. All participants will wear a non-invasive device throughout their entire study participation, to track heart rate, blood oxygen saturation, steps, sleep and monitor PEM. The primary feasibility objectives will be recruitment rates, intervention fidelity, adherence, acceptability (intervention and design), retention, blinding success and outcome completeness. Secondary objectives will include refined estimates for the standard deviation and correlation between baseline and follow-up measurements of fatigue. Feasibility and clinical outcomes will be collected at baseline, 4, 8, 12 and 24 weeks. Qualitative interviews with participants and physiotherapists will explore intervention acceptability and barriers/facilitators.<br><br>ETHICS AND DISSEMINATION: Ethical approval for this study was obtained by the Western University Health Sciences Research Ethics Board (REB# 123902). Dissemination plans include sharing of trial findings at conferences and through open access publications and patient/community channels.<br><br>TRIAL REGISTRATION NUMBER: NCT06156176.},
}
@article {pmid41213281,
year = {2026},
author = {Goxhaj, L and McCorkell, L and van Rhijn-Brouwer, F and Soares, L and Vogel, JM and de Canson, C},
title = {Negative results in long COVID clinical trials: choosing outcome measures for a heterogeneous disease.},
journal = {The Lancet. Infectious diseases},
volume = {26},
number = {1},
pages = {13-15},
doi = {10.1016/S1473-3099(25)00665-6},
pmid = {41213281},
issn = {1474-4457},
}
@article {pmid41213124,
year = {2025},
author = {Berry, C and McKinley, G and Bayes, HK and Anderson, D and Lang, CC and Gill, A and Morrow, A and Sykes, R and Taggart, D and Kamdar, A and Welsh, P and Dawkes, S and McConnachie, A and Gray, SR},
title = {Resistance Exercise Therapy After COVID-19 Infection: A Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {8},
number = {11},
pages = {e2534304},
pmid = {41213124},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; *COVID-19/rehabilitation/therapy/psychology ; Middle Aged ; *Resistance Training/methods ; Quality of Life ; Adult ; SARS-CoV-2 ; Walk Test ; Aged ; Exercise Tolerance ; Treatment Outcome ; *Exercise Therapy/methods ; },
abstract = {IMPORTANCE: Long COVID presents an unmet therapeutic need.<br><br>OBJECTIVE: To determine the effects of a resistance exercise intervention on exercise capacity, health status, and safety among adults after COVID-19 infection.<br><br>A 2-arm, multicenter, randomized clinical trial including 233 adults with a hospital or community diagnosis of COVID-19 infection in the preceding 12 months was undertaken from June 1, 2021, to April 26, 2024. The intervention group comprised 117 individuals, and the control group comprised 116 individuals. A total of 224 individuals at baseline and 193 individuals at 3 months completed Incremental Shuttle Walk Tests.<br><br>EXPOSURES: The intervention group received the personalized resistance exercise intervention for 3 months, and the control group received treatment as usual.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was the distance achieved (in meters) in the Incremental Shuttle Walk Test undertaken 3 months after randomization. Secondary outcome measures included health-related quality of life (measured by the European Quality of Life 5-Dimension 5-Level Instrument [EQ-5D-5L]), anxiety and depression (measured by the Patient Health Questionnaire), and grip strength.<br><br>RESULTS: A total of 233 adults (median age, 53.6 years [IQR, 43.8-60.8 years]; 146 women [62.7%]; 91 [39.1%] hospitalized with COVID-19 infection) were randomized (117 [50.2%] to the intervention group and 116 [49.8%] to the control group). The median percentage adherence with the exercise intervention was 71.0% (IQR, 47.8%-96.8%), equivalent to performing the exercises 5 days per week. The mean (SD) distance achieved in the Incremental Shuttle Walk Test was 328 (225) m for 224 individuals at baseline and 389 (249) m for 193 individuals at follow-up. The mean (SD) change in Incremental Shuttle Walk Test distance at 3 months compared with baseline was 83 (118) m in the intervention group (n&#x2009;=&#x2009;94) and 47 (95) m in the control group (n&#x2009;=&#x2009;98) (adjusted mean difference, 36.5 m [95% CI, 6.6-66.3 m]; P&#x2009;=&#x2009;.02). By 3 months, compared with the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 [95% CI, 0.01-0.11]; P&#x2009;=&#x2009;.02), Patient Health Questionnaire category (0.5 [95% CI, 0.2-0.8]; P&#x2009;=&#x2009;.01), and handgrip strength (2.6 kg [95% CI, 0.9-4.2 kg]; P&#x2009;=&#x2009;.002).<br><br>CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a 3-month program of resistance exercise among adults after COVID-19 infection appeared to improve walking distance, health-related quality of life, anxiety, depression, and grip strength. This pragmatic intervention may be a generalizable therapy for individuals with persisting physical symptoms after COVID-19 infection.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04900961.},
}
@article {pmid41212631,
year = {2025},
author = {Goodfellow, H and Blandford, A and Bradbury, K and Gomes, M and Hamilton, F and Henley, W and Stevenson, F and Fernandez-Reyes, D and Hurst, J and Heightman, M and Pfeffer, P and Ricketts, W and Singh, R and Hylton, H and Linke, S and Bindman, J and Robson, C and Walker, S and Ismaila, H},
title = {Development and implementation of a digital health intervention in routine care for long COVID patients: a comprehensive synopsis.},
journal = {Health and social care delivery research},
volume = {13},
number = {39},
pages = {1-27},
doi = {10.3310/GJHG0331},
pmid = {41212631},
issn = {2755-0079},
mesh = {Humans ; *COVID-19/rehabilitation ; Male ; Female ; Telemedicine/organization &amp; administration ; Middle Aged ; SARS-CoV-2 ; Adult ; Patient Reported Outcome Measures ; United Kingdom ; Aged ; State Medicine ; Digital Health ; },
abstract = {BACKGROUND: By July 2020, large numbers of post-COVID patients were experiencing symptoms for weeks or months, but traditional National Health Service models of rehabilitation service delivery could not meet demand.<br><br>OBJECTIVES: Design and deploy a digital health intervention to provide digitally delivered, remotely supported rehabilitation to long COVID patients on complicated and evolving pathways.<br><br>METHODS: The multidisciplinary team combined established research methods based on engineering and computer science (considering safety, stability and user requirements) with those based on biomedical and health service research (considering effectiveness and population impact). Qualitative data comprised recordings of meetings between study team members and clinicians and semistructured interviews with clinician and patient users. Quantitative data comprised referral, registration and usage rates; demographic and clinical characteristics of patients; and patient-reported outcome measures.<br><br>RESULTS: We created a modifiable digital health intervention, 'Living With COVID Recovery[TM] developed by Living With Ltd', London, UK, that continues to be used by National Health Service trusts. The digital health intervention included integration into a clinical pathway, a clinician-facing dashboard, two-way messaging and a patient-facing app with information and evidence-based treatments. We aimed to register 1000 users. By study completion on 20 December 2022, there were 9781 patients invited, of whom 7679 (78.5%) had registered, at 33 National Health Service clinics.<br><br>LIMITATIONS: Data came from patients at long COVID clinics, however data were unlikely to be representative of people with long COVID. We could not observe clinics under lockdown and had limited access to patient digital health intervention users or to people not engaging with the digital health intervention. Patient user data were incomplete, with inconsistent patient-reported outcome measure and other questionnaire data completion and no data on initial severity of disease, vaccination status, comorbidities or other individual circumstances.<br><br>CONCLUSIONS: Long COVID can be extremely debilitating, comparable to stage IV lung cancer in relation to fatigue and health-related quality of life. Care and rehabilitation should address the management of fatigue and reflect the impact of social disadvantage on symptom severity. With sufficient resources, a digital health intervention can be developed quickly and effectively using agile methodology and bringing together a genuinely multidisciplinary team, including, importantly, an industry partner. Digital health intervention product design and deployment are both important in getting National Health Service trusts, healthcare professionals and patients to engage with a digital health intervention. Projects should work closely with all user groups. Lockdown and the unmet need of a new patient group encouraged those who might otherwise have been reluctant to try a digital health intervention. Many patients and clinics accepted this digital remote support, which helped patients feel cared for while reducing strain on health services. This may encourage acceptance of other digital health intervention, although medical record integration remains a deterrent to clinics.<br><br>FUTURE WORK: This research focused on the development, deployment and evaluation of a digitally enabled rehabilitation programme for long COVID. Clinical effectiveness will be assessed within the Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways (UCL, London, UK) study.<br><br>FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132243.},
}
@article {pmid41212544,
year = {2026},
author = {Knopman, DS and Koltai, D and Laskowitz, DT and Becker, J and Charvet, L and Wisnivesky, J and Federman, A and Silverstein, A and Lokhnygina, Y and Pilloni, G and Haddad, M and Mahncke, H and Van Vleet, T and Huang, R and Cox, W and Terry, D and Karwowski, J and McCray, N and Lin, JJ and McComsey, GA and Singh, U and Geng, LN and Chu, HY and Reece, R and Moy, J and Arvanitakis, Z and Parthasarathy, S and Patterson, TF and Gupta, A and Ostrosky-Zeichner, L and Parsonnet, J and Kiriakopoulos, ET and Fong, TG and Mullington, J and Jolley, S and Shah, NS and Morimoto, SS and Lee-Iannotti, JK and Killgore, WDS and Dwyer, B and Stringer, W and Isache, C and Frontera, JA and Krishnan, JA and O'Steen, A and James, M and Harper, BL and Zimmerman, KO and , },
title = {Evaluation of Interventions for Cognitive Symptoms in Long COVID: A Randomized Clinical Trial.},
journal = {JAMA neurology},
volume = {83},
number = {1},
pages = {49-59},
pmid = {41212544},
issn = {2168-6157},
mesh = {Humans ; Female ; *COVID-19/complications/psychology ; Male ; Middle Aged ; *Cognitive Behavioral Therapy/methods ; *Cognitive Dysfunction/etiology/therapy/rehabilitation ; Adult ; *Transcranial Direct Current Stimulation/methods ; Aged ; Treatment Outcome ; },
abstract = {IMPORTANCE: Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need.<br><br>OBJECTIVE: To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID.<br><br>This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID.<br><br>INTERVENTIONS: Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks.<br><br>MAIN OUTCOMES AND MEASURES: Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days.<br><br>RESULTS: A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, -0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, -0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, -0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, -0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions.<br><br>CONCLUSIONS AND RELEVANCE: This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05965739.},
}
@article {pmid41210966,
year = {2025},
author = {Poyatos, P and Gratacós, M and Aguilar, D and Luque, N and Bonnin-Vilaplana, M and Eizaguirre, S and Cascante, M and Orriols, R and Tura-Ceide, O},
title = {Transcriptomic profiling of endothelial progenitor cells in post-COVID-19 patients: Insights at 3 and 6-month post-infection.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113731},
pmid = {41210966},
issn = {2589-0042},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant global morbidity since 2019. Long COVID, characterized by persistent symptoms after acute infection, may involve endothelial injury. We analyzed endothelial colony-forming cells (ECFCs) from post-COVID-19 patients at 3- and 6-month post-infection, comparing them with healthy controls and stratifying by prior pulmonary embolism (PE). Transcriptomic profiling identified differentially expressed genes (DEGs) associated with endothelial homeostasis, inflammation, oxidative stress, and thrombosis. Post-COVID ECFCs showed downregulation of NOS3, KLF2, ANGPT1, PIK3R3, GBX2, GDF6, SMAD6, SRC, and TGFB1, and upregulation of CASP1, CXCL5, IL12A, SOD2, TIMP3, and TLR2. Minimal differences were observed between 3 and 6-month samples. PE patients showed downregulation of thrombosis-related genes such as PTGS2 and ACKR3. These findings indicate sustained endothelial dysfunction and inflammation up to 6 months post-infection, highlighting the importance of long-term monitoring and potential therapeutic strategies to support vascular health in post-COVID-19 patients.},
}
@article {pmid41206715,
year = {2026},
author = {Wegwarth, O and Hertwig, R},
title = {Short report: association between self-reported COVID-19 experience and contemptuous beliefs about pandemic management among German citizens and healthcare professionals.},
journal = {Journal of public health (Oxford, England)},
volume = {48},
number = {1},
pages = {332-337},
doi = {10.1093/pubmed/fdaf144},
pmid = {41206715},
issn = {1741-3850},
support = {//Siemens Caring Hands e.V./ ; },
abstract = {BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of public adherence to pandemic management measures. Contempt for these measures could undermine compliance in future pandemics. This study explored associations between self-reported COVID-19 experiences and contemptuous beliefs about COVID-19 pandemic management.<br><br>METHODS: A cross-sectional online survey study was conducted in September 2024 with 964 German citizens and 423 healthcare professionals from respondi panels (Cologne, Germany). Respondents reported their attitudes toward eight contemptuous statements regarding COVID-19 pandemic management and their personal COVID-19 experiences, including infection, vaccine side effects, long COVID, and patient care (for professionals). Associations were analyzed using logistic regression and Mann-Whitney U tests.<br><br>RESULTS: Citizens with self-reported experience of COVID-19 infections were less likely to hold contemptuous beliefs (OR: 0.58; 95% CI: 0.39-0.85; P&#xa0;=&#xa0;.005), while those with experience of vaccine side effects were considerably more likely (OR: 1.50; 95% CI: 1.10-1.92; P&#xa0;=&#xa0;.009). Long COVID had no significant effect. Among professionals, not having cared for COVID-19 patients doubled the likelihood of contempt (OR: 2.10; 95% CI: 1.28-3.45; P&#xa0;=&#xa0;.003).<br><br>CONCLUSION: Findings suggest that experiential factors may contribute to belief formation-an area with limited empirical attention but potential relevance for addressing societal polarization.},
}
@article {pmid41205594,
year = {2025},
author = {Shahbaz, S and Osman, M and Syed, H and Mason, A and Rosychuk, RJ and Cohen Tervaert, JW and Elahi, S},
title = {Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS.},
journal = {Cell reports. Medicine},
volume = {6},
number = {11},
pages = {102449},
pmid = {41205594},
issn = {2666-3791},
mesh = {Humans ; Female ; Male ; *COVID-19/immunology/complications/genetics ; Gene Expression Profiling ; Middle Aged ; Adult ; *Fatigue Syndrome, Chronic/immunology/genetics/complications ; *Transcriptome ; Sex Factors ; Cytokines/metabolism ; Sex Characteristics ; SARS-CoV-2 ; Biomarkers ; Inflammation ; },
abstract = {Long COVID (LC) manifests with sex-specific differences, particularly in those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study reveals that female LC patients (LCF) with ME/CFS show a shift toward myelopoiesis, reduced lymphocytes, increased neutrophils/monocytes, and depleted regulatory T cells-suggesting persistent immune activation. Elevated CD71[+] erythroid cells and disrupted erythropoiesis contribute to fatigue and tissue damage in LCF. Cytokine profiling indicates a stronger pro-inflammatory response in LCF compared to males (LCM), along with markers of gut barrier dysfunction. Hormonal analysis shows reduced testosterone in LCF and estradiol in LCM. Transcriptomic data reveal neuroinflammatory signatures in LCF, potentially explaining cognitive symptoms. We also identify biomarkers that distinguish LCF from LCM and correlate with sex-specific clinical symptoms. Overall, LC with ME/CFS is characterized by sex-specific immune, hormonal, and transcriptional alterations, with females exhibiting more severe inflammation. These insights underscore the need for sex-tailored interventions, including consideration of hormone replacement therapy.},
}
@article {pmid41204293,
year = {2025},
author = {Prasad, PA and Hubbard, CC and Cenzer, I and Boscardin, J and Weerahandi, H},
title = {Health service use and work related outcomes in older adults with functional and cognitive impairments during the COVID-19 pandemic.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3846},
pmid = {41204293},
issn = {1471-2458},
support = {Project ID140673V//California Department of Public Health CPR3 program/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Aged ; Longitudinal Studies ; *Cognitive Dysfunction/epidemiology ; Middle Aged ; *Functional Status ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Pandemics ; SARS-CoV-2 ; },
abstract = {BACKGROUND: The COVID-19 pandemic had a lasting global health impact, with many survivors facing Long Covid. Older adults, already vulnerable to disability and cognitive decline, may also experience long-term challenges after COVID-19 infection. This study explores whether a history of COVID-19 infection interacts with pre-existing impairments in older adults, focusing on its effects on health services and work-related outcomes.<br><br>METHODS: This longitudinal cohort study used data from the Health and Retirement Study (HRS), spanning 2018 to 2022. Participants&#x2009;&#x2265;&#x2009;50&#xa0;years old in 2018 with documented functional and cognitive status scores and self-reported presence or absence of COVID-19 infection were included. Functional status was assessed using the Functional Limitation score, and cognitive status using the Crimmins cognitive scale or Langa scale if the HRS respondents were represented by a proxy. Health services use and work outcomes were evaluated using the 2022 HRS survey. Multivariable logistic regression models examined the association between baseline functional and cognitive status and outcomes, controlling for COVID-19 history, 2018 functional or cognitive status, age, gender, marital status, number of chronic conditions, household size, graduation from high school, and self-report of COVID-19 vaccination.<br><br>RESULTS: The study included 8,621 respondents. Those with severe functional limitations in 2018 were more likely to report health services use in 2022, irrespective of COVID-19 history. COVID-19 history did not significantly interact with baseline functional or cognitive impairments when evaluating health services use, ability to work, or disability benefit access. While older adults with moderate or severe functional limitations were more likely to report hospitalizations and nursing home stays, these outcomes were not significantly different based on COVID-19 history.<br><br>CONCLUSIONS: In this cohort of older adults, the relationship between baseline functional and cognitive impairment with health services use, ability to work, or disability benefit access did not significantly vary by self-reported COVID-19 infection history. While COVID-19 may have long-term impacts on older populations, our data suggest that infection history alone did not amplify the effects of pre-existing impairments in those who survived the pandemic. Further research using validated measures of persistent symptoms is needed to understand how Long Covid may manifest in older adults.},
}
@article {pmid41204118,
year = {2025},
author = {Scolari, FL and Spinardi, J and Silva, MMDD and Trott, G and Rodrigues, CO and Rover, MM and Souza, EM and Manfio, JL and Camargo, NI and Souza, AP and Souza, D and Carli, RF and Roldão, ES and Mocellin, D and Miozzo, AP and Silva, GND and Souza, JMB and Santos, RDRMD and Itaqui, CR and Rech, GS and Irineu, VM and Francisco, SC and Silvestre, O and Neves, PDMM and Tramujas, L and Nobre, V and Carvalho, SM and Ferreira, CDDA and Oliveira, JC and Royer, CA and Luiz, RM and Baura, VA and Gradia, DF and Brandalize, APC and Pereira, HA and Poitevin, CG and Robinson, CC and Barreto, BB and Schvartzman, PR and Marcolino, M and Antonio, ACP and Polanczyk, CA and Maccari, JG and Nasi, LA and Valluri, SR and Julião, VW and d'Hellencourt, FL and Kyaw, MH and Castillo, GDCM and Falavigna, M and Rosa, RG},
title = {Impact of long COVID phenotypes on quality of life following symptomatic omicron infection in Brazil: a machine learning analysis.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1523},
pmid = {41204118},
issn = {1471-2334},
mesh = {Humans ; Female ; Brazil/epidemiology ; *COVID-19/epidemiology/psychology/virology ; *Quality of Life ; Male ; Adult ; *Machine Learning ; Middle Aged ; Prospective Studies ; Phenotype ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: This study aimed to identify phenotypes of long COVID symptoms in adults following Omicron infection and assess their association with health-related quality of life (HRQoL).<br><br>METHODS: We analyzed three prospective observational studies in Brazil, enrolling adult patients who sought care for symptomatic Omicron infection between December 2021 and March 2023. The infection was confirmed by either an antigen test or reverse transcriptase polymerase chain reaction. Long COVID symptoms were assessed three months after enrollment through structured interviews. Phenotypes of Long COVID-19 were identified using a machine learning-based clustering approach. Exploratory analyses were conducted to examine predisposing factors and health-related quality of life utilities, measured by EQ-5D-3&#xa0;L, associated with each phenotype.<br><br>RESULTS: A total of 2,989 patients were analyzed (39% women, median age 41 years, and 96% had completed the primary series of COVID-19 vaccination). Long COVID symptoms at three months were reported by 1,155 (38.6%) patients. Three phenotypes were identified: cluster 1 (n&#x2009;=&#x2009;459 [39.7%]), characterized by a median of three symptoms (IQR, 2-5) with memory loss (80.4%), concentration problems (38.3%) and fatigue (35.7%) being most common; cluster 2 (n&#x2009;=&#x2009;549 [47.5%]), characterized by a median of two symptoms (IQR, 1-4) with fatigue (43.7%), other symptoms (42.3%), and cough (20.6%) being most common; and cluster 3 (n&#x2009;=&#x2009;147, 12.7%), characterized by a higher number of symptoms (median, 8; IQR, 7-10), with fatigue (89.9%), memory loss (88.4%), and anxiety (64.6%) as the most common. The mean EQ-5D-3&#xa0;L utility at 3 months was 0.75 for cluster 1, 0.73 for cluster 2, and 0.59 for cluster 3 (p&#x2009;<&#x2009;0.001). After adjusted regression analysis, cluster 3 was independently associated with the lowest EQ-5D-3&#xa0;L utilities (mean difference, -0.21; 95%CI, -0.24 to -0.18; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Distinct phenotypic presentations of Long COVID following Omicron infection in Brazil were identified, with significant differences in quality of life.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid41204001,
year = {2025},
author = {Kuodi, P and Shibli, H and Zayyad, H and Wertheim, O and Wiegler, KB and Jabal, KA and Dror, AA and Nazzal, S and Glikman, D and Charlett, A and Edelstein, M},
title = {Optimizing the schedule of BNT162b2 COVID-19 against long COVID and associated quality of life losses.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {462},
pmid = {41204001},
issn = {2730-664X},
abstract = {BACKGROUND: The long-term impact of COVID-19 vaccination on post-acute COVID-19 symptoms and associated quality of life (QoL) changes remains incompletely described. This study aimed to explore the impact of the timing of COVID-19 priming and booster doses, on reporting long COVID symptoms and associated QoL changes.<br><br>METHODS: Individuals who had PCR testing for SARS-CoV-2 processed in government hospitals in Northern Israel between 15[th] March 2021 and 15[th] June 2022 were invited to answer serial online surveys collecting information on SARS-CoV-2 infection, vaccination status and post-acute symptoms every 3-4 months for two years. Participants were categorized into groups based on the number of doses received prior to infection. We compared these groups over time in terms of reporting post-COVID symptom clusters and QoL, using population-average and mixed-effects regression models, respectively.<br><br>RESULTS: A total of 4809 individuals are enrolled and respond to up to five follow-up surveys. Of these, 1377 (28.61%) report a positive SARS-CoV-2 test, while 3432 (71.39%) report a negative result. After adjustment for potential confounders, receiving at least three COVID-19 vaccine doses prior to infection is associated with a 34% reduction in the likelihood of reporting at least one long COVID symptom cluster compared to being unvaccinated (adjusted odds ratio [aOR] = 0.66, p&#x2009;=&#x2009;0.022). Pre-infection vaccination is also associated with higher quality of life (QoL) scores (&#x3b2;&#x2009;=&#x2009;0.07, p&#x2009;<&#x2009;0.001). The estimated vaccine effectiveness of three pre-infection doses against long COVID over a two-year period is 26.5% (95% CI: 10.8-39.4). This protective effect remains stable over time. In contrast, vaccination received after infection shows no association with long COVID symptoms or QoL outcomes.<br><br>CONCLUSIONS: Receiving at least three COVID-19 vaccine doses prior to SARS-CoV-2 infection provides a sustained protective effect against long COVID and its negative impact on quality of life for at least two years. The longer-term durability of this protection, the role of reinfection, and the influence of emerging viral variants remains to be investigated.},
}
@article {pmid41202576,
year = {2025},
author = {Rottstädt, F and König, L and Seifert, C and Jesgarzewsky, T and Finke, K and Reuken, P and Stallmach, A and Vonderlind, S and Croy, I},
title = {Reduced interpersonal touch and elevated preferred interpersonal distance are signs of impaired social contact behavior in post-COVID syndrome.},
journal = {Journal of psychosomatic research},
volume = {199},
number = {},
pages = {112438},
doi = {10.1016/j.jpsychores.2025.112438},
pmid = {41202576},
issn = {1879-1360},
mesh = {Humans ; Female ; Male ; *COVID-19/psychology/complications ; Middle Aged ; *Interpersonal Relations ; Adult ; *Psychological Distance ; *Touch ; Depression/psychology/etiology ; Fatigue/psychology ; *Social Interaction ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Personal Satisfaction ; },
abstract = {BACKGROUND: Increased inflammation often evokes an adaptive sickness behavior with social withdrawal. We aimed to test whether reduced social contact also characterizes Post-COVID syndrome, a condition that is hypothesized to involve prolonged inflammation following SARS-CoV-2 infection.<br><br>METHODS: We queried 49 Post-COVID patients (mean age&#xa0;=&#xa0;46.8&#xa0;years, 38 (77.6&#xa0;%) female, mean duration of disease&#xa0;=&#xa0;16&#xa0;months) and 49 age- and gender-matched healthy control paricipants for their satisfaction with socializing, frequency of interpersonal contact and touch, and preferred interpersonal distance. Additionally, severity of fatigue and depressive mood were assessed in all participants.<br><br>RESULTS: While Post-COVID patients did not differ significantly from healthy controls in the frequency of general interpersonal contact, they reported a markedly lowered satisfaction with socializing (p&#xa0;<&#xa0;.01, &#x3b7;[2]&#xa0;=&#xa0;0.27). Specifically, touch frequency and desire for touch were reduced, with the largest difference observed for interactions with friends (p&#xa0;<&#xa0;.001, &#x3b7;[2]&#xa0;=&#xa0;0.13). Furthermore, Post-COVID patients reported approximately a 50&#xa0;% increase in preferred interpersonal distance towards others in order to feel comfortable (p&#xa0;<&#xa0;.001, &#x3b7;[2]&#xa0;=&#xa0;0.17). Mediation analyses suggest that those deviations were primarily driven by fatigue rather than depressive symptoms in Post COVID patients.<br><br>CONCLUSIONS: Over the course of the disease, the observed impairments are concerning, as they deprive patients of social contact as a source of dyadic coping and mental health. Pacing strategies should be adapted to explicitly incorporate social contact as a key element. The findings also align with the sickness behavior theory.},
}
@article {pmid41202571,
year = {2026},
author = {Ahmed, S and Greenberg, J and Kenney, R and Marini, C and Hyman, S and Fung, S and Edeoga, N and Baltazar, M and Grossman, SN and Seixas, A and Jean-Louis, G and Osorio, RS and Condos, R and Frontera, J and Gonzalez-Duarte Briseno, MA and Galetta, SL and Balcer, LJ and Thawani, SP},
title = {Autonomic dysfunction and quality of life in a cohort of neurology outpatients with post-acute sequelae of COVID-19, a two-year follow-up study.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {143},
number = {},
pages = {111719},
doi = {10.1016/j.jocn.2025.111719},
pmid = {41202571},
issn = {1532-2653},
mesh = {Humans ; *Quality of Life ; Female ; Male ; *COVID-19/complications/psychology ; Middle Aged ; Follow-Up Studies ; Adult ; *Autonomic Nervous System Diseases/etiology/psychology/epidemiology ; Aged ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; Outpatients ; Young Adult ; Cohort Studies ; Surveys and Questionnaires ; },
abstract = {PURPOSE: Many studies estimate that more than 50% of non-hospitalized patients with long-COVID develop moderate to severe autonomic dysfunction. However, the specific impact of autonomic dysfunction as it relates to quality of life in long-COVID is not fully understood. The aim of the current study is to assess autonomic symptoms and quality-of-life in patients with Post-Acute Sequelae of COVID-19 (PASC) recruited from a neurology department outpatient setting.<br><br>METHODOLOGY: In a two-year follow-up study of a baseline cohort of 93 non-hospitalized SARS-CoV-2 laboratory-positive patients evaluated for PASC between November 2020-August 2021, 44 participants completed follow-up telephone questionnaires examining quality-of-life as well as neurologic and autonomic symptoms.<br><br>RESULTS: Among 93 participants, 44 (47&#xa0;%) completed the two-year follow-up evaluation and 27 (61&#xa0;%) were female with a median age of 55&#xa0;years (IQR&#xa0;=&#xa0;24-88). Most participants (95&#xa0;%, 42/44) were vaccinated against COVID-19 and 43&#xa0;% (19/44) had a pre-existing neurological disorder. Median time from index COVID-19 infection to follow-up was 26&#xa0;months (IQR&#xa0;=&#xa0;23-17), with a median of 15&#xa0;months (IQR&#xa0;=&#xa0;15-16) between visits. Fatigue, word finding difficulty, and changes in memory were the most commonly reported PASC symptoms. Sixty-six percent (29/44) of individuals met criteria for autonomic dysfunction as defined by the Composite Autonomic Symptom Score-31 (COMPASS-31) scale. Secretomotor and gastrointestinal subdomains demonstrated significant associations with Neuro-QoL metrics for Anxiety, Depression, and Fatigue. For every 1 additional PASC symptom reported at a follow-up study visit, there was an average increase of 1.5 points on the COMPASS-31 composite score. In addition, visual disturbances and sleep impairment were both associated with increased autonomic dysfunction.<br><br>CONCLUSION: The strong association between autonomic dysfunction and reduced QoL in PASC and the relation to insomnia, visual dysfunction, and functional impairment are valuable findings, reinforcing the clinical impact of these symptoms longitudinally after index COVID-19 infection.},
}
@article {pmid41201746,
year = {2026},
author = {Wander, PL and Awan, O and Neal, J and Seidel, I and Bell, KA and Cassell, A and Fattal, D and Ng, B and Pyne, ML and Rog, L and Helfand, M},
title = {Synopsis of 2024 VA Long COVID Clinical Guidance for U.S. Veterans: Part 1, Nervous System-Related Symptoms.},
journal = {Journal of general internal medicine},
volume = {41},
number = {3},
pages = {788-806},
pmid = {41201746},
issn = {1525-1497},
mesh = {Humans ; *COVID-19/therapy/complications/epidemiology/diagnosis ; United States/epidemiology ; *Veterans ; United States Department of Veterans Affairs/standards ; *Nervous System Diseases/therapy/diagnosis ; *Practice Guidelines as Topic/standards ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {DESCRIPTION: Long COVID is common and includes nervous system-related symptoms (e.g., autonomic dysfunction, cognitive impairment, fatigue, and pain). We sought to develop just-in-time evidence-informed guidance for nervous system-related Long COVID, a condition for which mature evidence is limited.<br><br>METHODS: The U.S. Veterans Affairs (VA) Veterans Health Administration (VHA) Long COVID Field Advisory Board commissioned an expert panel that worked with a GRADE methodologist to develop an evidence-to-decision framework for emergent conditions by applying core elements of the Standards for Developing Trustworthy Clinical Practice Guidelines and those of GRADE. We also convened a multidisciplinary writing group that identified a list of clinically relevant questions and commissioned an independent review and synthesis of existing evidence. The writing group conducted structured discussions and used this evidence base to make recommendations for evaluation and treatment ("Evidence-informed Recommendations"). For history-taking, physical exam, and commonly used, noninvasive diagnostic tests, statements were based on consensus determinations of useful and safe care ("Good Practice Statements"). We used a Whole Health Systems approach to support the development of guidance that was patient-centered, culturally appropriate, and available regardless of literacy or disability. Feedback was solicited from Veterans and other stakeholders. Where the published literature was insufficient, we used evidence from treatment of similar conditions.<br><br>RECOMMENDATIONS: We drafted 30 Evidence-informed Recommendations and 41 Good Practice Statements for nervous system-related Long COVID in Veterans and disseminated them VA-wide, targeting specialty care providers. More research on the effectiveness of diagnostic and therapeutic interventions is needed. In particular, evidence "borrowed" from other conditions and populations should be replaced or supplemented by evidence in Long COVID. Clinical guidance should be updated as this evidence becomes available.<br><br>KEY POINTS: QUESTION: How can clinicians provide evidence-informed care for nervous system-related Long COVID (e.g., autonomic dysfunction, cognitive impairment, fatigue, and pain)?<br><br>FINDINGS: We commissioned an independent rapid evidence review which&#xa0;found that evidence supporting the care of nervous system-related Long COVID symptoms was limited. Using available evidence and other considerations (e.g., costs, equity, and applicability to Veterans experiencing Long COVID), we drafted 30 Evidence-informed Recommendations and 41 Good Practice Statements for nervous system-related Long COVID.<br><br>MEANING: Although mature evidence was limited, this guidance can provide a framework for clinicians caring for patients with nervous system-related Long COVID. More research on the effectiveness of diagnostic and therapeutic interventions in Long COVID is needed.},
}
@article {pmid41200182,
year = {2025},
author = {Liu, H and Xu, Z and Karsidag, I and Wang, P and Weng, J},
title = {Immune cell communication networks and memory CD8[+] T cell signatures sustaining chronic inflammation in COVID-19 and Long COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1689507},
pmid = {41200182},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *CD8-Positive T-Lymphocytes/immunology ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; *Cell Communication/immunology ; Female ; Male ; *Immunologic Memory ; Middle Aged ; Chronic Disease ; Single-Cell Analysis ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: COVID-19, including its post-acute sequelae (Long COVID), is increasingly recognized as involving persistent immune dysregulation and chronic inflammation. Severe and prolonged disease states are often accompanied by sustained cytokine release, immune cell exhaustion, and ongoing cell-cell communication that shapes the inflammatory milieu. Among immune subsets, CD8[+] T cells play a central role in antiviral defense, yet the molecular mechanisms linking their dysfunction to prolonged inflammation remain incompletely understood.<br><br>METHODS: We analyzed 73,110 peripheral blood mononuclear cells (PBMCs) from individuals across four disease states (Healthy, Exposed, Infected, and Hospitalized) using single-cell RNA sequencing. Immune cell subsets were annotated, and T cell heterogeneity was profiled. Cytokine and inflammatory scores were calculated to assess immune activation. Differentially expressed genes (DEGs) underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Cell-cell communication was evaluated to map ligand-receptor networks. Additionally, nine machine learning models were trained on a bulk RNA-seq cohort, and the SHapley Additive exPlanations (SHAP) framework was applied to interpret key predictive genes.<br><br>RESULTS: Progressive disease severity was associated with a decline in T cell proportions, enrichment of pro-inflammatory myeloid cells, and elevated cytokine expression, particularly IL-32. Memory CD8[+] T cells showed increased exhaustion and inflammatory scores while maintaining a central position in MHC-I-mediated communication networks. Persistent activation of immune and metabolic pathways, including antigen presentation and oxidative phosphorylation, was observed in prolonged disease states. Seven genes (RPS26, RPS29, RPL36, RPL39, RPS28, RPS21, and CD3E) were identified as strong predictors of chronic immune dysregulation, with the XGBoost model achieving the highest AUC. SHAP analysis confirmed their contributions to disease classification.<br><br>CONCLUSION: This study maps the immune landscape of COVID-19 and Long COVID at single-cell resolution, revealing that persistent immune cell communication, particularly involving memory CD8[+] T cells, may sustain chronic inflammation beyond the acute phase. The identified molecular signatures offer potential biomarkers and therapeutic targets for mitigating post-viral inflammatory syndromes.},
}
@article {pmid41200018,
year = {2025},
author = {Feldman, C and Manentsa, N and Akpomiemie, G and Jabavu, A and Moller, K and Baskhar, E and Mtshazo, B and Edem, E and Sokhela, SM and Lalla-Edward, ST and Venter, WDF and Richards, GA},
title = {Pulmonary manifestations of long COVID in Johannesburg, South Africa.},
journal = {Southern African journal of infectious diseases},
volume = {40},
number = {1},
pages = {734},
pmid = {41200018},
issn = {2313-1810},
abstract = {BACKGROUND: There are few studies of long coronavirus disease (COVID) in low- and middle-income countries.<br><br>OBJECTIVES: This study investigated long-term pulmonary manifestations of long COVID among adults in Johannesburg, South Africa.<br><br>METHOD: This was a respiratory sub-study of a larger long COVID investigation. Cases with self-reported long COVID symptoms were recruited into four cohorts: prior asymptomatic infection, mild to moderate infection, hospitalised for severe infection and vaccinated prior to infection. Cases with respiratory comorbidity and/or well-characterised exposure to certain conditions (e.g. cigarette smoking) were excluded. Demographics, clinical features, spirometry, six-minute walk test (6MWT) and high-resolution computerised tomographic (HRCT) scan of the chest were recorded.<br><br>RESULTS: Of the 171 patients interviewed from the initial study, 36 with appropriate inclusion criteria were recruited a median of 2.1 years following their acute COVID-19 illness. Accordingly, the incidence of long COVID was 21.1% (36/171 patients) for the group as a whole and 5.9% (3/51), 25.0% (14/56), 37.8% (17/45) and 10.5% (2/19) for cohorts 1-4, respectively (p = 0.001). The major symptoms were tiredness and/or fatigue, shortness of breath and cough. Overall, 33 patients had abnormal 6MWT results, and 10 had abnormalities on spirometry; obstructive pattern in five, restrictive in three and mixed in two. Seven patients (six of whom were previously hospitalised) had probable/possible abnormalities compatible with long COVID on HRCT scan (p = 0.045).<br><br>CONCLUSION: This study documented respiratory abnormalities in patients as long as 2 years after prior SARS-CoV-2 infection, especially among those with severe prior infection.<br><br>CONTRIBUTION: This was among the first studies comprehensively documenting pulmonary abnormalities in patients with long COVID in South Africa.},
}
@article {pmid41199609,
year = {2025},
author = {Lee, C and Williams, P and Abrahams, A and Darbyshire, J and Davies, HE and De Kock, J and Esmer, U and Jones, SA and Newey, V and Scott, J and Smith, N and Winch, D and Master, H and Elkin, S and , },
title = {What Can We Learn Four Years On? A Multi-Centre Service Evaluation Exploring Symptoms, Functional Impact, Recovery and Care Pathways in Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70435},
pmid = {41199609},
issn = {1369-7625},
support = {//This study is independent research funded by the National Institute for Health and Care Research (NIHR) (LOng COvid Multidisciplinary consortium: Optimising Treatments and servIces acrOss the NHS [LOCOMOTION], Ref: COV-LT2-0016)./ ; },
mesh = {Humans ; Female ; *COVID-19/complications/therapy/psychology ; Male ; Middle Aged ; England ; Adult ; Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; Wales ; Activities of Daily Living ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long Covid (LC) is associated with long-term health impacts that require ongoing support from healthcare services. We aimed to gain insights into patients' perceptions of their ongoing symptoms of LC, the effect on daily living and vocation, perceptions of what helps with LC recovery, as well as LC care pathways and ongoing care needs.<br><br>METHODS: An online survey was sent to 513 participants who had used one of three LC services across England and Wales between 2020 and 2024. Participants were invited to share their experiences. We employed a mixed-methods approach for data analysis, synthesising findings from quantitative and qualitative data. All data shared between sites was de-identified.<br><br>RESULTS: 269 (52.4%) participants completed the survey. The mean age was 52.7 (sd&#x2009;&#xb1;&#x2009;12.0), 69.1% female and 55.0% were White-British. The mean duration since initial SARS-CoV-2 infection was over 3 years (1204.4&#x2009;&#xb1;&#x2009;275.7&#x2009;days). The Post-Covid Functional Status (PCFS) scale indicated that most participants (94.1%, n&#x2009;=&#x2009;253) had not fully recovered. When employing a global rate of change scale, 39.0% (n&#x2009;=&#x2009;96) of 246 responders indicated they are still making improvements with respect to their recovery; 40.7% (n&#x2009;=&#x2009;100) had plateaued, and 20.3% (n&#x2009;=&#x2009;50) reported a worsening trajectory. Those with ongoing symptoms described fatigue 83.0% (n&#x2009;=&#x2009;210), cognitive dysfunction 58.5% (n&#x2009;=&#x2009;148) and breathlessness or wheezing 43.9% (n&#x2009;=&#x2009;111) most frequently. Of those who responded, 20.8% (n&#x2009;=&#x2009;48) were 'working as prior to their initial LC infection' and 25.5% (n&#x2009;=&#x2009;59) were currently 'unable to work'. Almost half (44.3%; n&#x2009;=&#x2009;86) were no longer receiving care whilst also reporting unmet care needs. In total, 62.7% (n&#x2009;=&#x2009;126) of participants indicated unmet care needs, and qualitative analysis indicated five overarching domains as having an important impact on long-term LC recovery and ongoing healthcare needs. These were Living with LC, LC interventions and recovery, Approach to the delivery of care, Insufficient support and Suggestions and improvement.<br><br>CONCLUSION: This study indicates the extent to which individuals continue to experience ongoing symptoms of LC, including aspects related to recovery and vocational impact, highlighting the potential widening gap between the ongoing need to support those living with LC and the limited provision of care.<br><br>The survey was co-produced with Experts by Experience, who had previously attended an LC service and members of the Patient Advisory Group within the Locomotion Consortium. Collaboration and involvement continued throughout the study, including analysis, interpretation and writing processes.<br><br>CLINICAL TRIAL REGISTRATION: Study registration details are available at ClinicalTrials.gov: NCT05057260 and ISRCTN: 15022307.},
}
@article {pmid41199272,
year = {2025},
author = {Blomberg, B and Myklebust, NN and Oppegaard, O and Tøndel, C and Cox, RJ and Iversen, A and Lehmann, ME and Sandvig, A and Dahl, TB and Valderhaug, VD and Szodoray, P and Wilhelmsen, M and Kirsebom, BE and Glambek, M and Kaarbøe, O and Aukrust, P and Lie, RT and Langeland, N},
title = {Randomized trial of nirmatrelvir/ritonavir versus placebo for adults with acute COVID-19 to prevent long COVID: PanoramicNOR Trial.},
journal = {Trials},
volume = {26},
number = {1},
pages = {477},
pmid = {41199272},
issn = {1745-6215},
mesh = {Humans ; *Ritonavir/administration &amp; dosage/therapeutic use/adverse effects ; Adult ; Double-Blind Method ; *COVID-19 Drug Treatment ; *COVID-19/prevention &amp; control/complications ; *Antiviral Agents/administration &amp; dosage/therapeutic use/adverse effects ; Middle Aged ; Young Adult ; Adolescent ; Male ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Female ; Drug Combinations ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: The high prevalence of long-term persisting symptoms after COVID-19 (coronavirus disease 2019), termed long COVID or post-COVID-19 condition, even among those with mild initial disease, may have a large public health impact. Apart from avoiding infection, there is no proven prevention or treatment for long COVID. We will perform a randomized placebo-controlled clinical trial to assess whether treatment with the novel antiviral, nirmatrelvir and ritonavir (Paxlovid®) for acute COVID-19 can prevent the development of long COVID.<br><br>METHODS: This is a randomized double-blinded placebo-controlled trial that aims to recruit 2000 nonpregnant persons aged 18 to 64&#xa0;years with acute COVID-19 with positive PCR and/or antigen test and symptom duration of not more than 5&#xa0;days. Participants will be randomized 1:1 to a 5-day course of Paxlovid (two tablets 150-mg nirmatrelvir and one tablet 100-mg ritonavir twice daily) or a 5-day course of placebo (similar number of tablets of equal appearance). The primary endpoint will be persistent symptoms compatible with long COVID, assessed as the prevalence of a dichotomous variable corresponding to the presence (1) or absence (0) of one or more of the following symptoms: (i) fatigue, (ii) dyspnea, and (iii) cognitive symptoms (memory and/or concentration problems). The primary outcome will be evaluated at 3-month follow-up and then re-evaluated at 6, 12, and 24&#xa0;months.<br><br>DISCUSSION: As more than 750 million people with confirmed COVID-19 have survived globally, the potential burden of long COVID on societies is formidable. If a simple 5-day oral treatment course with nirmatrelvir/ritonavir is shown to prevent long COVID, it would be a highly attractive intervention at an individual level and a mitigation of its public health consequences.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT05852873. Registered on May 2023.},
}
@article {pmid41197399,
year = {2026},
author = {Mohanty, MC and Jawade, KS and Rane, SS and Dravid, A and Gurav, YK and Bhardwaj, SD and Borse, R and Bargaje, MD and Sawardekar, V and Gupta, TM and Varose, SY and Patil, AP and Redewad, N and Bandare, G and More, S and Bhor, VM and Doke, P and Abraham, P},
title = {Persistence of post-acute COVID-19 sequelae up to four years in patients with long COVID from Western India: A cross-sectional descriptive study.},
journal = {Journal of infection and public health},
volume = {19},
number = {1},
pages = {103028},
doi = {10.1016/j.jiph.2025.103028},
pmid = {41197399},
issn = {1876-035X},
mesh = {Humans ; *COVID-19/complications/epidemiology ; India/epidemiology ; Cross-Sectional Studies ; Male ; Adult ; Female ; Middle Aged ; Aged ; Post-Acute COVID-19 Syndrome ; Young Adult ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-Acute Sequelae of COVID-19 or Long COVID (LC) affects millions globally, with persistent immune, neurological, and cardiovascular symptoms posing challenges to healthcare. This study analyses clinical, demographic, and lifestyle differences between LC and recovered (RC) individuals residing in Western India, extending observations up to four years post-infection.<br><br>METHODS: A cross-sectional study was conducted in four urban setting tertiary-care hospitals of Western India. Individuals aged 19-70 with documented SARS-CoV-2 infection and persistent or fluctuating symptoms beyond four weeks, unexplained by other diagnoses were recruited in LC group. Recovered individuals with confirmed past infection, negative SARS-CoV-2 RT-PCR at the time of enrolment, and no lingering symptoms were recruited in RC group. The demographic, socio-economic, and clinical data were collected.<br><br>RESULTS: Severe acute COVID-19 patients were more frequent in the LC group (n&#x202f;=&#x202f;104) compared to the RC group (n&#x202f;=&#x202f;83), though both LC and RC had similar proportions of mild/moderate acute COVID-19 patients. Fatigue was the most persistent symptom (79.80&#x202f;%), followed by cough and anxiety. Respiratory, cardiovascular, neuro-psychiatric symptoms declined over time, while dermatological, ENT, gastrointestinal, and muscular symptoms fluctuated. LC patients predominantly had hypertension as comorbidity, lower SPO2, and higher pulse rates (p&#x202f;<&#x202f;0.0001). Rates of hospitalization for COVID-19 treatment were similar, but mechanical ventilation use was exclusively observed in LC patients (10.6&#x202f;%). Sedentary lifestyles were more frequent in LC (17.30&#x202f;%) vs. RC (6.02&#x202f;%, p&#x202f;=&#x202f;0.0248).<br><br>CONCLUSION: Our study is one of the few in Indian population showing occurrence of multiple LC symptoms after 3-4 years of infection. We report severity of COVID-19, use of Remdesivir and mechanical ventilation to be associated with increased odds of LC. Fatigue, cough and anxiety were the most common symptoms reported by LC participants. Our findings establish a much-needed baseline for understanding symptom progression in LC patients, emphasizing the need for targeted interventions and long-term monitoring.},
}
@article {pmid41196899,
year = {2025},
author = {Malambo, W and Sampa-Kawana, M and Chanda, D and Fwoloshi, S and Kaonga, P},
title = {Parametric survival analysis of long COVID among hospitalized patients in Zambia: A retrospective cohort study on the time to symptoms resolving.},
journal = {PLOS global public health},
volume = {5},
number = {11},
pages = {e0004679},
pmid = {41196899},
issn = {2767-3375},
abstract = {Long COVID refers to the continuation or emergence of new symptoms within three months after acute SARS-CoV-2 infection, lasting for at least two months. Although several studies have described COVID-19 sequelae, gaps remain in understanding the temporal dynamics of symptoms resolution - information crucial for patients management and recovery planning. This study evaluated the resolution of COVID-19-related symptoms over time and associated factors among hospitalized patients in Zambia. We conducted a retrospective cohort study among individuals discharged after COVID-19 hospitalization and attending follow-up care in 13 specialized clinics in Zambia from August-2020 to December-2022. Severe acute COVID-19 was defined as hospitalization requiring supplemental oxygen, ICU admission, and/or treatment with steroids/remdesivir. Time-to-symptoms resolution (i.e., survival time) and changes in underlying hazard rate were our primary and secondary outcomes, respectively. We estimated incidence rates, median survival time (onset-to-resolution), and factors associated with symptom resolution using survival analysis, including hazard ratios (HRs) and changes in the underlying hazard rate over time. Among 823 participants, 616 (84.3%) had severe acute COVID-19 illness; 50.6% were female, and median age was 54 years (IQR: 43-64). Overall, 597 (72.5%) had symptoms resolution at a median 51 person-days (IQR: 34-104). Most participants (59.4%) had baseline comorbidities, and 16.6% had received ≥1 COVID-19 vaccine dose. Symptoms resolved at a rate of 12.2 per 1,000 person-days. Severe acute COVID-19 was associated with slower symptom resolution (adjusted HR: 0.68, 95% CI: 0.50-0.92), while infection during the Omicron-predominant period compared to wild-type was associated with faster resolution (aHR: 2.71; 95% CI: 1.46-5.03). The hazard rate peaked around person-day 20 and declined thereafter, indicating a non-monotonic recovery pattern. COVID-19 symptoms resolved more rapidly during the first month of post-acute infection. Patients with persistent symptoms not resolved within this period may experience prolonged recovery, underscoring the need for targeted follow-up and supportive care.},
}
@article {pmid41196059,
year = {2025},
author = {Powers, JM and Leist, SR and Suryadevara, N and Zost, SJ and Binshtein, E and Abdelgadir, A and Mallory, ML and Edwards, CE and Gully, KL and Hubbard, ML and Zweigart, MR and Bailey, AB and Sheahan, TP and Crowe, JE and Montgomery, SA and Harkema, JR and Baric, RS},
title = {Mouse-adapted SARS-CoV-2 Omicron BA.5 infection induces post-acute lung fibrosis in BALB/c mice.},
journal = {Journal of virology},
volume = {99},
number = {11},
pages = {e0140625},
pmid = {41196059},
issn = {1098-5514},
support = {R01 AI110700/AI/NIAID NIH HHS/United States ; R01 AI157155/AI/NIAID NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; AI110700//National Institute of Allergy and Infectious Diseases/ ; P01 AI158571/AI/NIAID NIH HHS/United States ; AI157155//National Institute of Allergy and Infectious Diseases/ ; AI158571//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Animals ; Mice, Inbred BALB C ; *COVID-19/pathology/virology/immunology/complications ; *SARS-CoV-2/immunology/pathogenicity/genetics ; Mice ; Disease Models, Animal ; *Pulmonary Fibrosis/virology/pathology ; Antibodies, Viral/immunology ; Antibodies, Neutralizing/immunology ; Lung/pathology/virology ; Female ; Humans ; Antibodies, Monoclonal/immunology ; },
abstract = {UNLABELLED: Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1, subsequent Omicron sub-lineages have continued to emerge, challenging the development of intervention and prevention strategies, including monoclonal antibodies and vaccines. To better understand the pathogenic effects caused by Omicron BA.5 infection, we developed a mouse-adapted virus with overt disease burden in BALB/c mice. Acute disease was characterized by significant weight loss and lung dysfunction following high-dose challenges. In survivor animals that were followed through 107 days post-infection, subpleural fibrosis with associated tertiary lymphoid structures was noted. Serum from these mice demonstrated potent neutralization against BA.5, with substantially reduced neutralization titers against early epidemic, zoonotic, and more recent contemporary XBB.1.5 variants. Intervention with pre-clinical monoclonal antibodies revealed that robust protection from BA.5-induced lung disease was possible after prophylactic administration. Together, this model enables the investigation of therapeutic approaches for both acute and post-acute sequelae of COVID-19.<br><br>IMPORTANCE: To best combat the evolving landscape of SARS-CoV-2 variants of interest and variants of concern, the development of effective small animal models is of critical importance. Herein, we describe the development of a model system in BALB/c mice to study the effects of SARS-CoV-2 BA.5 S gene in both acute and chronic disease manifestations. Intriguingly, we determined that fibrotic lung disease with tertiary lymphoid structures was a prominent feature in the lungs of mice that survived through the acute phase of infection. This is a prominent concern in human patients that survive the initial infection insult. As such, and most critically, the model system presented here provides researchers with an effective pathway in which long COVID manifestations and potential interventions can be studied.},
}
@article {pmid41194817,
year = {2025},
author = {Dimitrakopoulou, A and Sarantaki, A and Nanou, CI and Georgakopoulou, VE and Taskou, C and Chouli, M and Diamanti, A},
title = {Long COVID-Related Fatigue During Pregnancy: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e93877},
pmid = {41194817},
issn = {2168-8184},
abstract = {Long sequelae of COVID-19 (Long COVID), or post-acute sequelae of SARS-CoV-2 infection, encompasses a wide range of persistent symptoms, with fatigue emerging as one of the most prevalent and disabling. Pregnant individuals may be uniquely susceptible to post-viral fatigue due to immunological and physiological adaptations during gestation. This review consolidates existing data regarding the prevalence, risk factors, and clinical implications of Long COVID-associated fatigue in pregnant individuals. A narrative review was conducted of studies examining fatigue among pregnant individuals with confirmed SARS-CoV-2 infection. Key outcomes included fatigue prevalence, symptom persistence, associated risk or protective factors, and comparisons with non-pregnant populations. Across both the acute and post-acute stages of COVID-19, fatigue emerged as a consistently common symptom. Its prevalence and persistence varied significantly across studies, partly due to heterogeneity in assessment tools and follow-up durations. Severe acute illness, hospitalization, obesity, and smoking during pregnancy were linked to a higher risk of prolonged fatigue, whereas anosmia appeared to act as a potential protective factor. In contrast, comorbidities such as hypertension, diabetes, and lung disease were not significantly linked to fatigue risk. No consistent associations were found with maternal age or alcohol use. Long COVID-related fatigue presents a substantial burden in pregnancy, with implications for maternal health, quality of life, and postpartum recovery. Early recognition, individualized care strategies, and public health interventions targeting modifiable risk factors are essential to support this vulnerable population. Ongoing research is essential to uncover underlying mechanisms and guide evidence-based clinical management.},
}
@article {pmid41192910,
year = {2025},
author = {Kobayashi, D and Ishikawa, K and Shibutani, K and Jinta, T and Otani, N and Mori, N},
title = {Deterioration of the Swallowing Function Among Patients with COVID-19: A Propensity Score-Matched Cohort Study.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6038-25},
pmid = {41192910},
issn = {1349-7235},
abstract = {Objective This study aimed to investigate whether the swallowing function deteriorates more significantly following coronavirus disease (COVID-19) infection in comparison to other viral respiratory infections in patients with mild to moderate (grade 2) COVID-19. Methods We conducted a propensity score-matched cohort study at St. Luke's International Hospital in Tokyo, Japan, from January 2010 to March 2024. Elderly patients (≥70 years) admitted for viral respiratory infections, including influenza and COVID-19, were included. Patients with suspected bacterial infections, patients who were incapable of oral intake at admission (including those with enteral nutrition and gastrostomy), and patients who died during hospitalization were excluded. The primary outcome was deterioration in the swallowing function, defined as downgrade in food texture category from admission to discharge. Results During the study period, 505 COVID-19 patients and 242 patients with other viral infections were admitted. The mean age was 81.7 years (±7.6) and 401 patients (53.7%) were male. Patients with COVID-19 showed a significantly higher rate of swallowing deterioration in comparison to patients with other viral infections (44.7% vs. 36.6%, p=0.04). Specifically, among patients who consumed a full diet at admission, those with COVID-19 had a higher rate of swallowing deterioration than those with other viral infections (41.9% vs. 31.7%, p<0.01). Conclusion COVID-19 was associated with a significant higher rate of downgrade in the food texture category in comparison to other viral respiratory infections, suggesting a potential impairment in the swallowing function. Given that this deterioration may contribute to prolonged hospitalization in COVID-19 patients, early intervention aimed at restoring and supporting swallowing function is warranted.},
}
@article {pmid41191586,
year = {2025},
author = {Rhodes, S and Douglas, C},
title = {Experiences of accessing primary care by those living with long Covid in New Zealand: A qualitative analysis.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0324489},
pmid = {41191586},
issn = {1932-6203},
mesh = {Humans ; New Zealand/epidemiology ; *COVID-19/epidemiology/therapy ; *Primary Health Care ; Female ; Male ; Middle Aged ; Qualitative Research ; Adult ; *Health Services Accessibility ; Aged ; SARS-CoV-2/isolation &amp; purification ; },
abstract = {BACKGROUND: Long Covid is the persistence of symptoms beyond 12 weeks following acute Covid-19 infection. It is estimated to affect one in ten people and can be extremely debilitating. With few publicly funded long Covid clinics, most people rely on primary care providers as a first point of contact. There is currently limited understanding of the experience of accessing primary health care by adults living with long Covid in New Zealand.<br><br>PURPOSE: To explore the experiences of accessing primary health care by adults living with long Covid.<br><br>METHODS: A narrative inquiry approach was used to capture participants lived experiences of accessing primary health care. Zoom interviews and discussions were conducted with study participants. The automatically generated transcripts were reviewed and corrected, and the collated data were analysed using Braun and Clarke's thematic analysis.<br><br>RESULTS: Eighteen people participated in the interviews. Codes were identified and, through an iterative process, themes were generated, reviewed, and named. The seven themes included lack of upskilling of primary care staff; let down by the Government; self-advocacy and its cost; and throwing money at it.<br><br>CONCLUSION(S): The picture painted by participants was bleak with a sense that the world had moved on from Covid-19 and left them behind, with some experiencing a lack of support in primary health care. Reducing the likely long-term health and economic burden of long Covid requires targeted investment and action by Government at every level, along with better utilisation of the allied health workforce in primary care.},
}
@article {pmid41191177,
year = {2025},
author = {Hajek, A and Blome, C and Yon, DK and Soysal, P and Gyasi, RM and Peltzer, K and Pengpid, S and König, HH},
title = {Long COVID and psychosocial factors among middle-aged and older adults. Results of the nationally representative German Ageing Survey.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {313},
pmid = {41191177},
issn = {1720-8319},
mesh = {Humans ; Male ; Female ; Aged ; *COVID-19/psychology/epidemiology ; Germany/epidemiology ; Middle Aged ; *Social Isolation/psychology ; Loneliness/psychology ; Aged, 80 and over ; *Depression/epidemiology/psychology ; *Aging/psychology ; Adult ; SARS-CoV-2 ; Personal Satisfaction ; Surveys and Questionnaires ; Sex Factors ; },
abstract = {BACKGROUND: In addition to the physical symptoms, long COVID can cause considerable psychological burden.<br><br>AIMS: To investigate the association of long COVID with depressive symptoms, loneliness, perceived social isolation and life satisfaction (also stratified by sex).<br><br>METHODS: Data from the most recent eighth wave of the nationally representative German Ageing Survey was used, encompassing community-dwelling individuals 43 years to 90 years, n&#x2009;=&#x2009;4,017 individuals in the analytic sample). Psychometrically sound tools were used to quantify the outcomes. Physician-diagnosed long COVID was used as independent variable. Adjusted (weighted) linear regressions with cluster-robust standard errors were used. Robustness checks were conducted.<br><br>RESULTS: Regressions adjusted for sociodemographic and lifestyle-related covariates showed that individuals with long COVID had consistently worse psychosocial outcomes compared to individuals without long COVID. However, after additionally adjusting for health-related covariates, only the association between long COVID and perceived social isolation remained significant (&#x3b2;&#x2009;=&#x2009;0.29, p&#x2009;<&#x2009;0.001). Stratified by sex, long COVID was significantly associated with higher social isolation scores among women (&#x3b2;&#x2009;=&#x2009;0.37, p&#x2009;<&#x2009;0.001), but not among men in the fully adjusted models.<br><br>DISCUSSION: Even after adjusting for a wide array of covariates, findings suggest that (female) individuals with long COVID have stronger feelings of not belonging to the society (compared to individuals without long COVID).<br><br>CONCLUSIONS: It may be beneficial to find ways to help such individuals feel included in society.},
}
@article {pmid41190342,
year = {2024},
author = {Osati, EFO and Nagu, TJ and Sangeda, RZ and Shayo, GA},
title = {Residual cardiopulmonary manifestations following COVID-19: a Tanzanian ambispective study.},
journal = {BMJ public health},
volume = {2},
number = {Suppl 1},
pages = {e002082},
pmid = {41190342},
issn = {2753-4294},
abstract = {INTRODUCTION: Residual COVID-19 sequelae create a public health concern as they add to the already heavy burden of non-communicable diseases. We set out to investigate the magnitude of residual cardiopulmonary manifestations postacute COVID-19 and their associated factors in Tanzania.<br><br>METHODS: This was an ambispective study conducted between 26 March 2021 and 30 July 2021, among 712 hospitalised adults confirmed with SARS-CoV-2 in five tertiary-level hospitals in Tanzania. Retrospective data were analysed to determine baseline characteristics of the patients during acute COVID-19 admission. This was linked to prospective data that were collected 2 years postacute hospitalisation with COVID-19 to determine cardiopulmonary complications among these patients. Radiological pulmonary abnormalities were assessed by contrasted CT scan. Lung function tests were measured using a spirometer. Pulmonary hypertension and heart failure were confirmed by a transthoracic echocardiography. Generalised estimating equations were used to assess the associations between sociodemographic factors, clinical characteristics, treatment modalities and residual cardiopulmonary sequelae.<br><br>RESULTS: About half 317/712 (44.5%) were diagnosed with residual cardiopulmonary complications. Approximately 54% of participants were male. Median age (IQR) was 60 (48-69) years. Cardiopulmonary sequelae were significantly associated with body mass index (BMI) &#x2265;25.0&#x2009;kg/m[2] compared with those with BMI <25.0 kg/m[2] (adjusted OR (aOR) (95%&#x2009;CI)=3.4 (2.47 to 4.84), p<0.001), smokers compared with non-smokers (aOR (95%&#x2009;CI)=2.39 (1.09 to 5.23), p=0.030] and among participants who did not receive steroids during the acute COVID-19 (aOR (95%&#x2009;CI)= 1.62(1.16 to 1.92), p=0.042].<br><br>CONCLUSION: The independent predictors of residual cardiopulmonary manifestations due to COVID-19 were overweight, cigarette smoking, hypoxia and non-use of steroids during the acute phase of COVID-19 disease. Public health interventions addressing weight reduction and smoking cessation in conjunction with steroid use in acute COVID-19 may largely reduce the incidence of cardiopulmonary long COVID-19.},
}
@article {pmid41189723,
year = {2025},
author = {Fineberg, D and Moreau, A and Schneider-Futschik, EK and Armstrong, CW},
title = {A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID.},
journal = {ACS pharmacology &amp; translational science},
volume = {8},
number = {10},
pages = {3411-3431},
pmid = {41189723},
issn = {2575-9108},
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID (LC) are increasingly recognized as debilitating postinfectious conditions that impact both individuals and society. Recent research highlights the potential of metformin, an antidiabetic agent, as a treatment for these syndromes by targeting their underlying mechanisms. This review assesses the effectiveness of metformin in ME/CFS and LC, which involve complex dysfunctions related to cytokines, glycolysis, ATP generation, oxidative stress, gastrointestinal microbiomes, and vascular endothelial function. Metformin, traditionally known for its antihyperglycemic properties may offer broader therapeutic benefits by influencing these pathological pathways. It works by inhibiting complexes I and IV of the electron transport chain, which reduces the strain on malfunctioning complex V and decreases the production of harmful free radicals. Additionally, metformin's impact on mTOR signaling could improve energy metabolism in ME/CFS and LC by downregulating an overactive but underperforming protein, thereby alleviating symptoms. Beyond the impact on cellular metabolism, metformin has shown to have anti-inflammatory, vascular, gastrointestinal, neuroprotective and epigenetic effects. We explore this impact of metformin and the potential role it could play to help people with ME/CFS. While metformin shows promise, it is unlikely to be a stand-alone solution. Instead, it may be part of a broader treatment strategy that includes other therapies targeting neurocognitive and autonomic impairments.},
}
@article {pmid41187495,
year = {2026},
author = {Demir Unal, E},
title = {A Neuroimmunological Axis between systemic autoimmunity and Parkinson's disease following long-COVID: A case series.},
journal = {Journal of neuroimmunology},
volume = {410},
number = {},
pages = {578795},
doi = {10.1016/j.jneuroim.2025.578795},
pmid = {41187495},
issn = {1872-8421},
mesh = {Humans ; Female ; Middle Aged ; *COVID-19/complications/immunology ; *Parkinson Disease/immunology/diagnostic imaging/etiology ; SARS-CoV-2 ; *Autoimmunity/immunology ; *Crohn Disease/immunology/diagnostic imaging/etiology ; Pandemics ; *Neuroimmunomodulation/immunology ; *Pneumonia, Viral/complications/immunology ; *Coronavirus Infections/complications/immunology ; },
abstract = {BACKGROUND: Long COVID, a multisystemic syndrome following SARS-CoV-2 infection characterized by persistent immune dysregulation, systemic inflammation, and neuroimmune dysfunction, is a significant area of investigation in the neurological sciences. The hypothesis that this pathophysiological state can trigger de novo autoimmune diseases and potentially accelerate underlying neurodegenerative processes is gaining traction. This case series aims to illuminate the potential neuroimmunological link between these conditions by presenting the patients who developed de novo Crohn's disease (CD) and ankylosing spondylitis (AS) following Long COVID and were subsequently diagnosed with post-COVID Parkinson's Disease (PD).<br><br>CASE PRESENTATIONS: The first case is a 50-year-old female who developed de novo CD six months after COVID-19 pneumonia, managed with the TNF-&#x3b1; inhibitor. Eighteen months later, she presented with parkinsonian motor deficits. The post-COVID PD diagnosis was supported by susceptibility-weighted MRI showing loss of nigrosome-1 and DAT-SPECT revealing a presynaptic dopaminergic deficit. The second case is a 48-year-old female who was diagnosed with de novo AS eight months post-COVID, treated with adalimumab. Twenty-six months later, she developed progressive bradykinesia and rigidity. Neuroimaging confirmed post-COVID PD with corresponding loss of nigrosome-1 and a presynaptic dopaminergic deficit on DAT-SPECT. In both genetically negative cases, dopaminergic therapy led to substantial motor improvement, with Unified Parkinson's Disease Rating Scale (UPDRS) Part IIIscores decreasing from 8 to 3 and 14 to 4, respectively.<br><br>CONCLUSION: This case series proposes a pathogenic cascade wherein SARS-CoV-2 infection acts as an environmental trigger, initiating a Long COVID-associated immune dysregulation that first precipitates a systemic autoimmune disorder. We hypothesize that this sustained inflammatory milieu subsequently accelerates the dysfunction of the dopaminergic system in predisposed individuals, thereby unmasking the clinical phenotype of post-COVID PD. This novel association highlights a potential nexus between virally-induced autoimmunity and subsequent neurodegeneration, offering a new perspective in the field of neuroimmunology.},
}
@article {pmid41186895,
year = {2025},
author = {Dihan, QA and Alshammari, N and Elhusseiny, AM and Rickels, KL and Shakarchi, AF and Chauhan, MZ and Sallam, AB},
title = {Long COVID and the development of new-onset uveitis: a large database study.},
journal = {Journal of ophthalmic inflammation and infection},
volume = {15},
number = {1},
pages = {79},
pmid = {41186895},
issn = {1869-5760},
abstract = {PURPOSE: To determine the impact of long COVID diagnosis on the risk of developing uveitis among individuals vaccinated and not vaccinated against COVID.<br><br>METHODS: We conducted a population-based retrospective cohort study using an aggregate healthcare database, TriNetX, which includes data from over 127 million patients across 95 international healthcare organizations. Four cohorts were compared: (1) Unvaccinated, Long COVID; (2) Unvaccinated, No Long COVID; (3) Vaccinated, Long COVID; and (4) Vaccinated, No Long COVID. Patients with any history of uveitis prior to initial COVID diagnosis were excluded. The primary outcome was the risk of new-onset uveitis at 1 and 2 years following the diagnosis of long COVID.<br><br>RESULTS: Unvaccinated, long COVID patients demonstrated an increased risk of developing new-onset uveitis compared to unvaccinated, no long COVID controls at 1 year (aHR: 2.01, 95% CI: 1.19-3.38) and 2 years (aHR: 1.60, 95% CI: 1.08-2.37). The highest risk was seen for anterior uveitis at 1 year (aHR: 1.96, 95% CI: 1.13-3.41) and 2 years (aHR: 1.59, 95% CI: 1.06-2.40). Other uveitis subtypes did not show an increased risk in this cohort. Among vaccinated individuals, there was not increased risk in those with long COVID compared to those without at 1 year (aHR: 0.95, 95% CI: 0.58-1.55) and 2 years (aHR: 0.97, 95% CI: 0.65-1.46).<br><br>CONCLUSION: Unvaccinated individuals with long COVID have an increased risk of developing new uveitis, particularly anterior uveitis. Vaccinated individuals with long COVID did not have an increased risk of developing uveitis compared to vaccinated non-long COVID individuals.},
}
@article {pmid41184874,
year = {2025},
author = {Laursen, CH and Nielsen, TB and Leth, S and Schiøttz-Christensen, B and Nielsen, CV and Langagergaard, V and Sørensen, L and Sørensen, D and Oestergaard, LG},
title = {Characterising disability in patients with long COVID-does gender matter? an analytic cross-sectional study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3744},
pmid = {41184874},
issn = {1471-2458},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Middle Aged ; *Activities of Daily Living ; Sick Leave/statistics &amp; numerical data ; Adult ; Sex Factors ; *Persons with Disabilities/statistics &amp; numerical data ; Denmark/epidemiology ; Employment/statistics &amp; numerical data ; Aged ; },
abstract = {BACKGROUND: Long COVID affects patients' daily functioning and activity participation. However, gender-specific differences remain insufficiently explored despite well-documented effects of gender on health outcomes. This study examines gender differences in sociodemographic characteristics, employment status, sick leave, and mental fatigue among individuals with long COVID. Furthermore, this study explores self-reported and prioritised problems with activities of daily living (ADL) across genders and compares patterns between women and men. We hypothesised that traditional gender roles would manifest in distinct challenges for women and men.<br><br>METHODS: We included 780 individuals (567 women and 213 men) diagnosed with long COVID who were referred to occupational therapy at a Danish outpatient clinic for long COVID. Sociodemographic characteristics, employment status, and sick leave were self-reported. Mental fatigue was assessed using the Mental Fatigue Scale, and ADL problems using the Canadian Occupational Performance Measure. A qualitative deductive content analysis was conducted to further categorise prioritised ADL problems.<br><br>RESULTS: A higher proportion of women than men had higher education (55% vs. 37%). No statistically significant gender difference was seen in the prevalence of sick leave (57% vs. 50%). Moderate to severe mental fatigue was reported by 78% of women and 68% of men, with women reporting significantly higher fatigue (p&#x2009;<&#x2009;0.001). Minor gender differences in ADL problems were observed, with more women reporting difficulties in household management, quiet recreation, and social interaction. Both women and men prioritised similar ADL problems, such as paid work, physical activity, social interaction, and fulfilling caregiving roles.<br><br>CONCLUSION: ADL challenges reported by women and men were largely similar and had a significant impact on their daily lives. Identifying key activity limitations is essential to inform effective rehabilitation strategies.},
}
@article {pmid41183079,
year = {2025},
author = {Konishi, K and Yamamoto, S and Sada, RM and Asano, K and Onozuka, D and Tanaka, S and Miyazawa, S and Kinoshita, M and Kutsuna, S},
title = {Research to evaluate safety and impact of long COVID intervention with Ensitrelvir for National Cohort (RESILIENCE Study): A protocol for a randomized, double-blind, placebo-controlled trial.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0335609},
pmid = {41183079},
issn = {1932-6203},
mesh = {Humans ; Japan/epidemiology ; Double-Blind Method ; *COVID-19/virology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Randomized Controlled Trials as Topic ; Registries ; Cohort Studies ; Indazoles ; Triazines ; Triazoles ; },
abstract = {This study was registered with the Japan Registry of Clinical Trials on February 16, 2024 (jRCTs051230184, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs051230184).},
}
@article {pmid41182495,
year = {2025},
author = {Pini, L and Guerini, M and Giordani, J and Levi, G and Latronico, N and Piva, S and Peli, E and Benoni, R and Pini, A and Zucchi, G and Piras, S and El Masri, Y and Visca, D and Caminati, M and Senna, G and De Ciuceis, C and Rosei, CA and Muiesan, ML and Tantucci, C},
title = {24-Month assessment of respiratory function in patients hospitalized for severe SARS-CoV-2 pneumonia: a follow-up study.},
journal = {Internal and emergency medicine},
volume = {20},
number = {8},
pages = {2455-2462},
pmid = {41182495},
issn = {1970-9366},
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/complications/epidemiology ; Middle Aged ; Italy/epidemiology ; Follow-Up Studies ; Aged ; Respiratory Function Tests/methods/statistics &amp; numerical data ; Adult ; Hospitalization/statistics &amp; numerical data ; },
abstract = {Long COVID affects multiple body systems, with the respiratory system being particularly vulnerable. This study aimed to analyze the lung ventilatory function and diffusion capacity of patients with severe SARS-CoV-2 pneumonia during a 24-month follow-up course. Ventilatory function and lung diffusion capacity were assessed 6, 12, 18, and 24 months after hospital discharge. Ventilatory parameters, Diffusion Lung Carbon Monoxide (DLCO), and KCO (Carbon Monoxide transfer coefficient) normalization were defined as achieving values > 80% predicted. A total of 222 patients admitted to the Intensive Care Unit (ICU) at ASST Spedali Civili di Brescia, Brescia, Italy, were enrolled. Among the 172 patients who completed the study, 140 (63%) achieved normalization of ventilatory parameters, DLCO, and KCO. The median time to recovery was 4.5 months, and the hazard ratio (HR) decreased by 2% for each year of age increase. The median time to normalize ventilatory parameters (VC, FVC, FEV1, FEV1/FVC, TLC, and KCO) was 1.5 months, while the median time to alveolar volume (VA) normalization was 4.5 months. Male gender reduces the odds of normalization for FEV1/FVC and VA. The median time to DLCO normalization was 9 months, with HR reduced by 3.1% as each year of age increased and augmented by 226% in obese subjects. 24 months after severe COVID pneumonia, 14% of patients had persistent ventilatory and/or diffusive defects. Our study documented that male sex, age, and obesity impact the odds of normalization of ventilatory function and diffusive capacity. These findings underline the chronic nature of lung damage following severe COVID-19 pneumonia and the need for long-term follow-ups.},
}
@article {pmid41181095,
year = {2025},
author = {Simón-Rueda, A and Sánchez-Menéndez, C and Casado, G and Fuertes, D and Murciano-Antón, MA and Mateos, E and Domínguez-Mateos, S and Pozo, F and García-Pérez, J and Pérez-Olmeda, M and Cervero, M and Massanella, M and Moncunill, G and Torres, M and Coiras, M},
title = {Immune dysregulation and endothelial dysfunction associate with a pro-thrombotic profile in Long COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1613195},
pmid = {41181095},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications/blood/virology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Biomarkers/blood ; Aged ; Adult ; *Thrombosis/immunology ; Cohort Studies ; *Endothelium, Vascular/immunology ; Antibodies, Viral/blood ; Blood Coagulation ; },
abstract = {INTRODUCTION: Long COVID (LC) affects approximately 10% of individuals post-SARS-CoV-2 infection, with symptoms persisting beyond 12 weeks. The underlying mechanisms remain unclear, and current models often focus on pre-existing comorbidities.<br><br>METHODS: This cohort study aimed to identify robust biomarkers and clarify LC pathogenesis through a comprehensive analysis performed in 32 LC individuals 26 months post-infection compared with 35 fully recovered individuals recruited between March and July 2022. Blood and fecal samples were collected, and multiple parameters associated with immune dysfunction, endothelial damage, bacterial translocation, and coagulation alterations, alongside signs of viral persistence and sociodemographic and clinical features, were analyzed.<br><br>RESULTS: Although viral RNA was undetected on blood or stool, elevated plasma IgG against the nucleocapsid may indicate frequent reinfections, greater infection severity, or delayed immune normalization. Increased levels of prothrombin, thrombin, fibrinogen, sEPCR, and CRP pointed to persistent endothelial dysfunction and coagulation imbalance. Lower levels of the bactericidal protein REG3A suggest potential disruptions in mucosal immune response. We found no major differences in traditional comorbidities, highlighting that LC may stem from distinct pathogenic mechanisms beyond pre-existing conditions. Importantly, our study revealed impaired humoral immunity and identified an association between vaccine heterogeneity and increased LC risk, emphasizing the relevance of consistent vaccination strategies. A Random Forest model using the measured biomarkers achieved 100% accuracy in classifying LC individuals, reinforcing their diagnostic potential.<br><br>DISCUSSION: These findings support a multifactorial model of LC involving immune dysregulation and persistent endothelial damage that led to coagulation abnormalities and a pro-thrombotic profile, supporting that LC is more closely related to a sustained, uncontrolled inflammatory response rather than immunodeficiency, and underscoring the value of multidimensional biomarker profiling for guiding clinical management and prevention strategies.},
}
@article {pmid41179091,
year = {2025},
author = {Tadisina, S and Mohammed, S and Asad, R and Tselovalnikova, T and Nguyen, B and Akella, PV and Abu Kishk, M},
title = {Prevalence and Evolution of Thyroid Dysfunction in COVID-19: A Retrospective Study.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93542},
pmid = {41179091},
issn = {2168-8184},
abstract = {Objective Coronavirus-19 (COVID-19) is known to mainly affect the respiratory system, but it has also been found to impact multiple endocrine systems. Various studies have shown a relationship between thyroid dysfunction and COVID-19 infection. However, there is controversy around thyroid-inflammatory autoimmune conditions contributing to a worse prognosis of COVID-19 infection. The main objective of our single-center retrospective study is to evaluate the prevalence and evolution of thyroid dysfunction in patients with COVID-19 infection. Methods A total of 615 adults with confirmed COVID-19 infection, between March 2020 and December 2023, who had thyroid function tests (TFTs), were included in the study. Patients with pre-existing thyroid disease or on medications affecting thyroid function were excluded. Thyroid dysfunction was defined as any abnormality in TFTs. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 26 (Released 2018; IBM Corp., Armonk, NY, USA). Differences in continuous variables were assessed using independent sample t-tests, and Pearson's Chi-square tests were used to compare categorical variables. Results The study showed that 84 patients (13.6%) had thyroid dysfunction. The most common abnormalities were non-thyroidal illness syndrome (NTIS, n = 39; 46.4%) and subclinical hypothyroidism (n = 37; 44%), followed by overt hyperthyroidism (n = 6; 7.1%) and overt hypothyroidism (n = 2; 2.3%). The evolution of thyroid dysfunction was followed for about one year by chart review and showed no progression to overt thyroid dysfunction. Conclusion We noted that thyroid dysfunction is not uncommon in patients with COVID-19, with subclinical hypothyroidism and NTIS being the most prevalent findings. These abnormalities are often transient and resolve without progression in most cases. The pathogenesis appears to involve both direct viral effects and systemic inflammatory responses. Given the potential overlap between thyroid dysfunction and long COVID symptoms, selective monitoring of thyroid function is warranted in symptomatic individuals.},
}
@article {pmid41178423,
year = {2025},
author = {Limami, Y and Wahnou, H and Ndayambaje, M and Hba, S and Chgari, O and Ammara, M and El Kebbaj, R and Naya, A and Oudghiri, M and Duval, RE},
title = {SARS-CoV-2: A Liver Brief.},
journal = {WIREs mechanisms of disease},
volume = {17},
number = {6},
pages = {e70005},
doi = {10.1002/wsbm.70005},
pmid = {41178423},
issn = {2692-9368},
mesh = {Humans ; *COVID-19/complications/virology/pathology/immunology ; *SARS-CoV-2/pathogenicity ; *Liver Diseases/virology/pathology ; *Liver/virology/pathology/immunology/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Virus Internalization ; },
abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has revealed the virus's ability to induce multi-organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID-19 patients are explored, focusing on direct viral infection, immune-mediated damage, and the gut-liver axis. SARS-CoV-2 enters liver cells through the Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre-existing liver conditions, such as metabolic-associated fatty liver disease (MAFLD), alcohol-related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID-19 patients. Post-COVID-19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug-Induced Liver Injury (DILI) from COVID-19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS-CoV-2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver-related complications in both acute and Long COVID-19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.},
}
@article {pmid41177912,
year = {2025},
author = {Rhidenour, KB and Thompson, CM and Babu, S and Kelpinski, LF},
title = {"Everything Looks Normal": Patient Narratives of Contested Legitimacy in Long COVID Medical Encounters.},
journal = {Health communication},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/10410236.2025.2580322},
pmid = {41177912},
issn = {1532-7027},
abstract = {This study examines how individuals with long COVID navigate illness experiences when faced with normal test results. Through qualitative analysis of 1,043 posts from r/covidlonghaulers between July 2020 and January 2021, we identified four key themes: overlapping diagnostic possibilities increase confusion, discordance in treatment plans, sustained uncertainty, and challenges to credibility. Our findings reveal how polysemic meanings of normal become sites of tension between biomedical evidence and lived experiences, creating a communicative burden for patients who must advocate for legitimacy and care. The analysis demonstrates how overlapping symptomology with other conditions complicates diagnosis, while patients develop strategies to navigate dismissive healthcare encounters and establish credibility when symptoms persist despite normal results. Reddit served as a vital platform for patients to exchange communication strategies for healthcare encounters and find validation when test results invalidated their experiences. A strength of this study is its ability to capture the experience of people with long COVID at the community's inception through a platform that connected them despite geographical barriers. Our findings provide valuable insights into how patients navigate contested illness experiences and offer concrete pathways for enhancing patient-provider communication around medically unexplained symptoms across various diagnoses.},
}
@article {pmid41176968,
year = {2025},
author = {Thaweethai, T and Gross, RS and Pant, DB and Rhee, KE and Jernigan, TL and Kleinman, LC and Snowden, JN and Salisbury, AL and Kinser, PA and Milner, JD and Tantisira, K and Warburton, D and Mohandas, S and Wood, JC and Fitzgerald, ML and Carmilani, M and Krishnamoorthy, A and Reeder, HT and Foulkes, AS and Stockwell, MS and , },
title = {Preventive effect of vaccination on long COVID in adolescents with SARS-CoV-2 infection.},
journal = {Vaccine},
volume = {68},
number = {},
pages = {127907},
pmid = {41176968},
issn = {1873-2518},
support = {U24 DA041147/DA/NIDA NIH HHS/United States ; U01 DA051039/DA/NIDA NIH HHS/United States ; U01 DA041120/DA/NIDA NIH HHS/United States ; U01 DA051018/DA/NIDA NIH HHS/United States ; U01 DA041093/DA/NIDA NIH HHS/United States ; U24 DA041123/DA/NIDA NIH HHS/United States ; U01 DA051037/DA/NIDA NIH HHS/United States ; U01 DA051016/DA/NIDA NIH HHS/United States ; U01 DA041106/DA/NIDA NIH HHS/United States ; U01 DA041117/DA/NIDA NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; U01 DA041174/DA/NIDA NIH HHS/United States ; U01 DA051038/DA/NIDA NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; U01 DA041134/DA/NIDA NIH HHS/United States ; U01 DA041022/DA/NIDA NIH HHS/United States ; U01 DA041156/DA/NIDA NIH HHS/United States ; U01 DA050987/DA/NIDA NIH HHS/United States ; U01 DA041025/DA/NIDA NIH HHS/United States ; U01 DA050989/DA/NIDA NIH HHS/United States ; U01 DA041089/DA/NIDA NIH HHS/United States ; U01 DA050988/DA/NIDA NIH HHS/United States ; U01 DA041028/DA/NIDA NIH HHS/United States ; U01 DA041048/DA/NIDA NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; U01 DA041148/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; Adolescent ; *COVID-19/prevention &amp; control/epidemiology/immunology ; Male ; Female ; *COVID-19 Vaccines/administration &amp; dosage/immunology ; *Vaccination ; Child ; SARS-CoV-2/immunology ; United States/epidemiology ; Disease Progression ; },
abstract = {PURPOSE: In adolescents (12-17 years), it is unknown whether COVID-19 vaccination reduces progression from COVID-19 to Long COVID (LC) beyond preventing SARS-CoV-2 infection. We assessed the effect of vaccination among SARS-CoV-2 infected adolescents.<br><br>METHODS AND RESULTS: Participants were recruited from over 60 US healthcare and community settings. The exposure was any COVID-19 vaccination 6&#xa0;months prior to infection. The outcome was LC defined using the LC research index. Vaccinated (n&#xa0;=&#xa0;724) and unvaccinated (n&#xa0;=&#xa0;507) adolescents were matched on sex, infection date, and enrollment date. The risk of LC was 36&#xa0;% lower (95&#xa0;% CI, 17&#xa0;%, 50&#xa0;%) in vaccinated compared to unvaccinated participants.<br><br>CONCLUSIONS: Vaccination reduces the risk of LC. Given the profound impact LC can have on the health and well-being of adolescents and the limited availability of treatments during this developmental stage, this supports vaccination as a strategy for preventing LC by demonstrating an important secondary prevention effect.},
}
@article {pmid41176305,
year = {2026},
author = {Palacio, A and Bast, E and Phillip, P and Milanes, I and Klimas, N and Tamariz, L},
title = {Virtual Group Clinics Improve Self-Reported Long COVID Symptoms Among Veterans: Results From a Holistic Care Approach.},
journal = {Journal of the American Medical Directors Association},
volume = {27},
number = {1},
pages = {105963},
doi = {10.1016/j.jamda.2025.105963},
pmid = {41176305},
issn = {1538-9375},
}
@article {pmid41174646,
year = {2025},
author = {He, Z and Yi, S and Zhou, H and Hu, F and Nie, Q and Song, D and Liu, X and Wang, J and Zhou, J and Liu, J and Li, Y and Xu, L and Ou, Y and Mei, Y and Zeng, D and Cheng, G and Liu, D},
title = {Exploring the association between the post-pandemic period and psychological problems among university students in Wuhan: a cross-sectional analysis.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3715},
pmid = {41174646},
issn = {1471-2458},
support = {No. 81870901//National Natural Science Foundation of China/ ; No. 81870901//National Natural Science Foundation of China/ ; No. 2020355//Hubei Teaching Program/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Students/psychology/statistics &amp; numerical data ; China/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Universities ; Young Adult ; Adult ; *Anxiety/epidemiology ; Surveys and Questionnaires ; *Depression/epidemiology ; Sleep Initiation and Maintenance Disorders/epidemiology ; Pandemics ; Prevalence ; Adolescent ; SARS-CoV-2 ; },
abstract = {OBJECTIVE: Evidence demonstrates that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection influences mental health through biological, psychological, and social mechanisms. In the post-pandemic period, defined as the time following the easing of major public health restrictions and the return to normalcy in daily life, university students represent a vulnerable population, experiencing a high prevalence of psychological problems due to the lingering influence of the pandemic on daily life and the emergence of long-term health consequences. There is an urgent need to understand these mental health symptoms and quantify their associated factors.<br><br>METHODS: A questionnaire was designed to investigate the mental health symptoms of anxiety, depression, and insomnia among university students in Wuhan, focusing on four key domains: individual, family, school, and pandemic. Logistic regression was employed to analyze the related factors and conduct attribution analysis.<br><br>RESULTS: Of the 2,668 eligible participants, 2,112 (79.2%) self-reported Omicron infection, and 352 (16.7%) experienced Long-COVID. The prevalence of moderate-to-severe depression was 18.2% (95% CI: 16.8%-19.7%), anxiety was 8.9% (95% CI: 7.8% -&#x2009;10.0%) and insomnia was 31.4% (95% CI: 29.6%-33.1%). Moderate-to-severe psychological symptoms among university students were associated with ten factors across the four key domains, with total weighted Population Attributable Fractions (PAFs) accounting for 60.1% of depression, 40.8% of anxiety, and 61.6% of insomnia. Individual factors had the highest PAFs, contributing 31.2% to depression, 23.8% to anxiety, and 25.1% to insomnia, followed by pandemic-related PAFs of 17.7% ,10.3%, and 21.9% for depression, anxiety, and insomnia, respectively.<br><br>CONCLUSION: The psychological challenges confronting university students in Wuhan are alarmingly severe, with individual factors superimposed on the pandemic caused by SARS-CoV2 being the primary contributors. We propose targeted intervention measures: strengthening psychological counseling services, increasing communication and exchange to enhance students' psychological resilience, raising awareness about mental health and lifestyle, alleviating students' fear of sequelae, assisting university students with academic planning and career guidance, cultivating adaptability, and promoting overall physical and mental health.},
}
@article {pmid41174473,
year = {2025},
author = {Abiri, E and Hemmatian, N},
title = {Investigating apoptosis in peripheral blood mononuclear cells among the elderly in the post-COVID-19 era.},
journal = {BMC immunology},
volume = {26},
number = {1},
pages = {86},
pmid = {41174473},
issn = {1471-2172},
mesh = {Humans ; *COVID-19/immunology/pathology ; Aged ; *Apoptosis/immunology ; *Leukocytes, Mononuclear/immunology ; Male ; Female ; *SARS-CoV-2/immunology ; Cross-Sectional Studies ; Aged, 80 and over ; Membrane Potential, Mitochondrial ; Caspase 3/metabolism ; Immunosenescence ; },
abstract = {BACKGROUND AND AIM: The COVID-19 pandemic has left a lasting imprint on immune function, particularly in the elderly-a population already vulnerable to immunosenescence. While acute and long-COVID immune responses have been widely studied, the long-term apoptotic behavior of peripheral blood mononuclear cells (PBMCs) remains underexplored. This study aims to investigate the legacy of SARS-CoV-2 on PBMC apoptosis in elderly individuals during the post-COVID era, shedding light on potential persistent immune dysregulation.<br><br>MATERIALS AND METHODS: In this cross-sectional study, PBMCs were isolated from peripheral blood samples of elderly individuals (>&#x2009;65 years old) with a documented history of COVID-19 infection at least six months prior. Using multiparametric flow cytometry, we quantified early and late apoptosis markers (Annexin V/PI), mitochondrial membrane potential disruption (&#x394;&#x3a8;m), and expression of pro-apoptotic (Bax, Caspase-3) and anti-apoptotic (Bcl-2) proteins. Statistical analyses were performed to assess intergroup differences and correlations with clinical history. This study was conducted in 2025.<br><br>RESULTS: Elderly post-COVID individuals exhibited a significantly elevated proportion of apoptotic PBMCs compared to controls (p&#x2009;<&#x2009;0.01), particularly within the CD4&#x2009;+&#x2009;and CD8&#x2009;+&#x2009;T-cell subsets. Mitochondrial depolarization and increased Bax/Bcl-2 ratios indicated a shift toward intrinsic apoptotic pathways. Caspase-3 activation was also heightened in the post-COVID group. Notably, apoptotic burden correlated with time since infection and severity of initial illness.<br><br>DISCUSSION: Our findings suggest a prolonged apoptotic signature in the immune cells of elderly individuals following recovery from COVID-19. These alterations may reflect a sustained immune exhaustion or maladaptive remodeling of lymphocyte populations, potentially contributing to impaired immunosurveillance and increased vulnerability to secondary infections or chronic inflammatory conditions.<br><br>CONCLUSION: COVID-19 may cast a long immunological shadow in the elderly, with persistent PBMC apoptosis representing a novel facet of post-viral immune dysregulation. Flow cytometry reveals a unique apoptotic phenotype that could serve as a biomarker for long-term immune health and guide post-pandemic clinical management strategies for aging populations.},
}
@article {pmid41173504,
year = {2025},
author = {Briggs, AH and Ibbetson, A and Walters, A and Houchen-Wolloff, L and Armstrong, N and Emerson, T and Gill, R and Hastie, C and Little, P and Overton, C and Pimm, J and Poinasamy, K and Singh, S and Walker, S and Leavy, OC and Richardson, M and Elneima, O and McAuley, H and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Greening, NJ and Harrison, E and Docherty, A and Lone, NI and Quint, JK and Chalmers, J and Ho, LP and Horsley, AR and Raman, B and Wain, LV and Brightling, CE and Marks, M and Evans, RA and , },
title = {Clinical and cost-effectiveness of diverse posthospitalisation pathways for COVID-19: a UK evaluation using the PHOSP-COVID cohort.},
journal = {BMJ open respiratory research},
volume = {12},
number = {1},
pages = {},
pmid = {41173504},
issn = {2052-4439},
mesh = {Humans ; *COVID-19/economics/therapy/epidemiology ; Cost-Benefit Analysis ; United Kingdom/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Quality of Life ; Quality-Adjusted Life Years ; SARS-CoV-2 ; Adult ; Prospective Studies ; Patient Discharge/economics ; Health Care Costs/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Long covid has emerged as a complex health condition for millions of people worldwide following the COVID-19 pandemic. Previously, we have categorised healthcare pathways for patients after discharge from hospital with COVID-19 across 45 UK sites. The aim of this work was to estimate the clinical and cost-effectiveness of these pathways.<br><br>METHODS: We examined prospectively collected data from 1013 patients at 12 months postdischarge on whether they felt fully recovered (self-report), number of newly diagnosed conditions (NDC), quality of life (EuroQoL-five dimension-five level (EQ-5D-5L) utility score compared with pre-COVID estimate) and healthcare resource costs (healthcare records). An analysis of the cost-effectiveness was performed by combining the healthcare resource cost and 1-year EQ-5D (giving a quality-adjusted life-year (QALY)) using statistical models that accounted for observed confounding.<br><br>RESULTS: At 1 year, 29% of participants felt fully recovered, and 41% of patients had an NDC. The most comprehensive services, where all patients could potentially access assessment, rehabilitation and mental health services, were more clinically effective when compared with either no service or light touch services (mean (SE) QALY 0.789 (0.012) vs 0.725 (0.026)), with an estimated cost per QALY of &#xa3;1700 (95% uncertainty interval: dominated to &#xa3;24 800).<br><br>CONCLUSION: Our analysis supports the need for proactive, stratified, comprehensive follow-up, particularly assessment and rehabilitation for adults after hospitalisation with COVID-19, showing these services are likely to be both clinically and cost-effective according to commonly accepted thresholds.},
}
@article {pmid41171518,
year = {2026},
author = {Mallouli, SZ and Munblit, D and Iakovleva, E and Winkler, AS and Fornari, A and Helbok, R and Struhal, W and Beretta, S and De Groote, W and Curatoli, C and Lanza, M and Ericka, F and Crivelli, L and Giussani, G and Wasay, M and Chakroun Walha, O and Safi, F and Leonardi, M and Allegri, R and Guekht, A and Triki, CC},
title = {Persistent neurological sequelae in children and adolescents after SARS-CoV-2: a scoping review.},
journal = {Infection},
volume = {54},
number = {1},
pages = {57-74},
pmid = {41171518},
issn = {1439-0973},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Humans ; Adolescent ; *COVID-19/complications/epidemiology ; Child ; *Nervous System Diseases/epidemiology/etiology/virology ; SARS-CoV-2 ; },
abstract = {OBJECTIVES: For the past five years, COVID-19 has not only been a priority for health planning but also a hotspot for clinical research. Yet, the weight of the worldwide COVID-19 pandemic arises from the critical phase consequences due to the onset of acute disease, associated containment measures, and documented ongoing disabling symptoms. Investigating the global longitudinal effects on children and adolescents will inform future health directives tailored to this population's needs. This review aimed to report the spectrum of persistent neurological sequelae in children and adolescents following SARS-CoV-2 infection.<br><br>METHODS: Hence, we conducted a scoping review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included the peer-reviewed articles from PubMed, Google Scholar, Web of Science, Cochrane Library, and WHO COVID database to identify relevant literature on long-COVID-19 neurological signs/symptoms among children and adolescents. The search covered the period between September 2020 and September 2024.<br><br>RESULTS: The results of our analysis of 33 studies found long-COVID-19-related neurological signs/symptoms were predominantly: pain and sensory problems (N&#x2009;=&#x2009;74,612/91,543; 81.5%), followed by sleep disturbances (N&#x2009;=&#x2009;14,630/91,543; 15.9%), and cognitive difficulties (N&#x2009;=&#x2009;2274/91,543; 2.4%). The global prevalence of long COVID-19 neurological signs/symptoms was estimated between 0.4% (20/5032; 95% CI&#x2009;=&#x2009;2.1-3%) and 34% (27/79) based on data obtained through online questionnaire; while it varied between 1.8% (4/215) and 83.14% (74/89; 95%CI&#x2009;=&#x2009;&#x2009;&#x2009;-&#x2009;&#x2009;0.12; 0.30) based on patient assessment. Long-COVID-19-related neurological signs/symptoms were more common in the 11-16 age group. Children with immunocompetent profiles were at higher risk of developing long-COVID-19-related neurological signs/symptoms.<br><br>CONCLUSION: Our results demonstrate a considerable burden of COVID-19-related persistent neurological signs/symptoms in children and adolescents, which should be taken into consideration in healthcare decision-making.},
}
@article {pmid41171293,
year = {2025},
author = {Anderer, S},
title = {Long COVID Trial Explores Anti-Inflammatory Treatment.},
journal = {JAMA},
volume = {334},
number = {21},
pages = {1875-1876},
doi = {10.1001/jama.2025.17537},
pmid = {41171293},
issn = {1538-3598},
}
@article {pmid41170051,
year = {2025},
author = {Jain, P and Paliwal, P and C Hundekari, J and Paliwal, M and Bajpai, T and Rajput, J and Mishra, K},
title = {Oxidative stress markers among post-Covid-19 survivors in Central India.},
journal = {Bioinformation},
volume = {21},
number = {7},
pages = {1922-1924},
pmid = {41170051},
issn = {0973-2063},
abstract = {Oxidative stress is an important element in the pathophysiology of COVID-19 leading to the development of post-COVID syndrome. Therefore, it is interest to evaluate the relationship between changes in oxidative status and the persistence of long-COVID symptoms. Our, data shows that the Superoxide dismutases and Serum Malondialdehyde (MDA) levels were low in cases than controls among post-Covid-19 srvivors.},
}
@article {pmid41169891,
year = {2025},
author = {Kamel, D and Vu, MH and Bender, J and Warburton, D and Wood, JC and Mohandas, S},
title = {Exploring long COVID in pediatric patients: clinical insights from a long COVID clinic.},
journal = {Frontiers in pediatrics},
volume = {13},
number = {},
pages = {1640747},
pmid = {41169891},
issn = {2296-2360},
abstract = {BACKGROUND: Long COVID describes the persistence or recurrence of symptoms beyond the acute phase of SARS-CoV-2 infection and is increasingly recognized in children and adolescents. Despite its prevalence, understanding of symptom patterns and the influence of vaccination on disease trajectory in pediatric populations remains limited.<br><br>METHODS: We conducted a retrospective study of patients aged 0-21 years evaluated at the Long COVID Clinic at Children's Hospital Los Angeles between August 2021 and November 2023. Patients were included if they reported persistent or new symptoms &#x2265;4 weeks after SARS-CoV-2 infection.<br><br>RESULTS: A total of 123 patients were enrolled. The mean age was 13.1 years, and 51% were male. Symptom onset occurred a mean of 5 weeks after infection. At presentation, 56% of patients reported symptoms lasting 0-24 weeks, 28% for 25-52 weeks, and 16% for >52 weeks. Fatigue (93%) and headache (70%) were the most prevalent symptoms in both younger (<12 years) and older (>12 years) cohorts. Female patients more frequently reported brain fog, dizziness, palpitations, and postural orthostatic tachycardia syndrome. Overall symptom burden decreased significantly over time (p&#x2009;<&#x2009;0.001). Vaccination status at baseline was not associated with difference in symptom duration on initial presentation (p&#x2009;=&#x2009;0.4). However, among those vaccinated after developing long COVID, 41% reported subjective improvement in the following weeks.<br><br>CONCLUSION: Pediatric long COVID is marked by prolonged, multisystem symptoms. Vaccination may offer symptomatic benefit for some patients, though larger prospective studies are necessary to better define its role.},
}
@article {pmid41168795,
year = {2025},
author = {Gartmann, J and Sturm, C and Bökel, A},
title = {Physiotherapy interventions in post- and long-COVID-19: a scoping review of the literature up to February 2023.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {1425},
pmid = {41168795},
issn = {1472-6963},
abstract = {BACKGROUND: Physiotherapy is an accepted and recommended treatment for post- and long-COVID-19 condition. It is assumed that physiotherapists reported a lack of information on physiotherapy interventions and treatment parameters. This scoping review provides an overview of the evidence on physiotherapy interventions published in the scientific literature.<br><br>METHODS: The scoping review includes studies analysing physiotherapy treatment parameters and interventions in post- and long-COVID patients. Studies focusing on telemedicine or exclusively home-based workouts are excluded. A systematic literature search was conducted by two independent researchers in the databases PubMed, EBSCO, SCOPUS, Web of Science, EMBASE, PEDro, Cochrane, and WISO. Following the abstract screening process, data extraction and critical assessment were performed.<br><br>RESULTS: In this scoping review, 6 studies were included, providing information physiotherapy management of post- and long-COVID-19. The research identified respiratory therapy, aerobic training or strength training as key areas of focus.<br><br>CONCLUSION: This scoping review highlights the need for further studies on physiotherapy treatment in post- and long-COVID condition.<br><br>TRIAL REGISTRATION: Open Science Framework (Registry number osf.io/5k3tA).<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-025-13631-7.},
}
@article {pmid41167719,
year = {2025},
author = {Twycross, A and le May, A and McMahon, A and Maxwell, E},
title = {Resources page: foundations of Nursing Care for People with Long Covid.},
journal = {Evidence-based nursing},
volume = {29},
number = {1},
pages = {3-4},
doi = {10.1136/ebnurs-2025-104419},
pmid = {41167719},
issn = {1468-9618},
}
@article {pmid41165819,
year = {2026},
author = {Helt, TW and Thomsen, RS and Christensen, J and Lund, TK and Kalhauge, A and Rönsholt, F and Podlekavera, D and Arndal, E and Lebech, AM and Berg, RMG and Katzenstein, TL and Mortensen, J},
title = {Relation of pulmonary diffusing capacity changes to HRCT chest and V/Q SPECT findings at short-term and intermediate follow-up after COVID-19: a prospective cohort study (The secure study).},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {53},
number = {3},
pages = {2178-2189},
pmid = {41165819},
issn = {1619-7089},
mesh = {Humans ; *COVID-19/diagnostic imaging/physiopathology ; Male ; Female ; Middle Aged ; Follow-Up Studies ; Prospective Studies ; *Tomography, X-Ray Computed ; *Tomography, Emission-Computed, Single-Photon ; Aged ; *Pulmonary Diffusing Capacity ; Adult ; *Lung/diagnostic imaging/physiopathology ; Time Factors ; },
abstract = {BACKGROUND: Several patients exhibit a severity-dependent reduced pulmonary diffusing capacity (DLCOc) following coronavirus disease 2019 (COVID-19) infection. This has been attributed to fibrosis-like restrictive lung disease, as shown by chest high-resolution computed tomography (HRCT), and concurrent ventilatory disturbances observed by ventilation-perfusion single-photon emission computed tomography (V/Q SPECT) imaging. The aim of this study was to investigate whether reductions in DL,COc at short- and intermediate-term follow-up were associated with initial severity of COVID-19, and to which extend this was linked to the presence of fibrosis-like abnormalities on HRCT and ventilatory disturbances on V/Q SPECT.<br><br>METHODS: A total of 153 patients diagnosed with COVID-19 between March 2020 and March 2021 were included in the study. The patients underwent lung function testing, chest HRCT, and V/Q SPECT at short-term (5.6 months) follow-up. Individuals exhibiting any evidence of post-COVID-19 sequelae (n&#x2009;=&#x2009;121) were also referred to intermediate follow-up (12.5 months).<br><br>RESULTS: At short-term follow-up, a severity dependent reduction in DL,COc was observed, which was not evident at intermediate follow-up. At both short-term and intermediate follow-up, HRCT showed ground-glass opacity (GGO) and fibrosis-like abnormalities related to disease severity. Most patients had V/Q defects mainly with ventilatory abnormalities, including both matched and inversely matched defects at both follow-up times.<br><br>CONCLUSION: The severity-dependent reduction in DL,COc at short-term follow-up, associated with restrictive lung function pattern, GGO and fibrosis on HRCT, and ventilatory disturbances on V/Q SPECT, showed spontaneous recovery by intermediate follow-up. However, the restrictive ventilatory disturbances and associated morphological changes persisted.},
}
@article {pmid41164784,
year = {2025},
author = {Jagannathan, P and Hedlin, H and Liang, JW and Shaw, B and Maestri, E and Lin, M and Utz, PJ and Singh, U and Geng, LN and Bonilla, H},
title = {Longitudinal Patient-Reported Outcome Trajectories in Long COVID: Findings From the STOP-PASC Clinical Trial.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf634},
pmid = {41164784},
issn = {2328-8957},
support = {UL1 TR001085/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Long COVID is a heterogeneous post-infectious condition. Although patient-reported outcome (PRO) measures for diagnosis or therapeutic monitoring have been adapted from related complex chronic illnesses, no PRO has been validated specifically in Long COVID. The STOP-PASC randomized, placebo-controlled trial of nirmatrelvir/ritonavir (NMV/r) in adults with Long COVID showed no overall treatment effect. This exploratory analysis aimed to identify distinct symptom trajectories and clinical characteristics associated with improvement or worsening over time.<br><br>METHODS: We performed latent class trajectory modeling (LCTM) on PRO measures-including the Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), PROMIS domains, and core symptoms-among 155 randomized participants. Participants were followed for 15&#x2005;weeks with serial symptom assessments. Trajectory groups were identified using Bayesian Information Criteria and characterized using descriptive statistics and absolute standardized differences.<br><br>RESULTS: LCTM revealed heterogeneity in symptom trajectories. Two groups emerged for PGIS (improving n = 17, persistent/severe n = 136) and PGIC (improving n = 130; worsening n = 22). PROMIS-Physical Function modeling identified four groups (improving, normal/mild, moderate, and severe), fatigue core symptom modeling identified three (improving; moderate; severe). Worsening groups had higher proportions of NMV/r-treated participants and greater prevalence of cardiovascular symptoms and low-dose naltrexone use. Improving groups had shorter time since infection and higher baseline physical function. No subgroup showed a clear benefit from NMV/r.<br><br>CONCLUSIONS: Distinct PRO trajectories reflect the clinical heterogeneity of Long COVID. NMV/r showed no clear benefit across subgroups. These findings emphasize the need for validated, Long COVID-specific PRO instruments and targeted therapeutic trials tailored to Long COVID subtypes.},
}
@article {pmid41164629,
year = {2025},
author = {Sekar, P and Dominic, M and Balakrishnan, S and Sreelakshmi, VK and Haneendhar, R and Gopan, SJ and Rathnasami, P and Moturi, SV},
title = {Post-COVID-19 Complications: A Study on Long COVID Symptoms and Their Pathophysiology.},
journal = {Journal of pharmacy &amp; bioallied sciences},
volume = {17},
number = {Suppl 3},
pages = {S2557-S2559},
pmid = {41164629},
issn = {0976-4879},
abstract = {BACKGROUND: Long COVID refers to persistent symptoms lasting weeks or months after recovery from acute COVID-19. These symptoms can affect multiple systems and impair quality of life.<br><br>OBJECTIVE: To assess the prevalence, pattern, and probable pathophysiological mechanisms of long COVID symptoms in recovered patients.<br><br>MATERIALS AND METHODS: A cross-sectional study was conducted over 12 months among 210 adults recovered from COVID-19 (&#x2265;12 weeks postinfection). Clinical evaluation, lab investigations, and imaging were used to identify post-COVID symptoms and explore underlying mechanisms.<br><br>RESULTS: Common symptoms included fatigue (67.6%), breathlessness (42.8%), cognitive issues (39.5%), and myalgia (34.7%). Neuropsychiatric complaints were noted in 41%, while 29% had cardiopulmonary sequelae. Elevated inflammatory markers correlated with symptom persistence (P < 0.05).<br><br>CONCLUSION: Long COVID involves diverse symptoms, primarily fatigue and neurorespiratory complaints. Immune dysregulation and systemic inflammation appear central to its pathophysiology.},
}
@article {pmid41164396,
year = {2025},
author = {Pierson, BC and Craig-Kuhn, MC and Stewart, L and Sercy, E and Stern, CA and Graham, B and Michel, A and Parmelee, E and Koehlmoos, TP and Saunders, D and Mancuso, JD and Pollett, S and Burgess, T and Tribble, DR},
title = {Evaluating the risk and risk factors of dysautonomia as a post-acute sequelae of COVID-19: a secondary analysis of a matched case-control dataset.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1653175},
pmid = {41164396},
issn = {1664-2295},
support = {Y01 AI005072/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: A significant proportion of patients presenting with post-acute sequelae of COVID-19 (PASC) have been found to meet diagnostic criteria for certain disorders of the autonomic nervous system. Substantial gaps remain in our understanding of these conditions. Our objective is to evaluate demographic and medical factors associated with PASC dysautonomia in active duty US Service members (ADSM). Additionally we assessed for risk factors in those diagnosed with COVID-19 for PASC dysautonomia, and differences in those with PASC dysautonomia and non-PASC dysautonomia.<br><br>METHODS: A matched case control dataset (n&#x202f;=&#x202f;1,367,961) of ADSM diagnosed with COVID-19 matched with ADSM with no evidence of COVID-19 was utilized to assess associations of demographic and clinical factors with PASC dysautonomia. Logistic regression modeling was used to assess differences among those diagnosed with COVID-19. Conditional logistic regression modeling using propensity score weighting was used for comparisons between those with PASC dysautonomia and non-PASC dysautonomia.<br><br>RESULTS: We identified 619,983 COVID-19 cases (158 PASC dysautonomia) and 747,978 controls (219 non-PASC dysautonomia). Among COVID-19 cases, factors positively associated with PASC dysautonomia were white, non-Hispanic race/ethnicity, female sex, younger age, northeast region, more severe COVID-19 infection, and comorbid depression or anxiety. Among those with dysautonomia, those with PASC dysautonomia were more likely to be of female sex, younger, in the northeast region, and less likely to have comorbid anxiety.<br><br>CONCLUSION: PASC dysautonomia is rare in ADSM but associated with increased care utility and often prolonged diagnostic pathways. Important demographic and COVID-19 specific risk factors are associated with the development of PASC dysautonomia. PASC dysautonomia has significant differences in risk factors as compared to non-PASC dysautonomia, warranting further examination. These findings may support clinician awareness and prognostication and prompt further research on the pathophysiology and management of these conditions.},
}
@article {pmid41164170,
year = {2025},
author = {Raveendran, VV and AlQattan, S and AlMutairy, E},
title = {A review on clinical implications of S100 proteins in lung diseases.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1618772},
pmid = {41164170},
issn = {2296-858X},
abstract = {The S100 family of proteins plays a pivotal role in the pathogenesis of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary arterial hypertension (PAH), pulmonary fibrosis, lung cancers, acute lung injury, acute respiratory distress syndrome, COVID-19, and lung transplantation. This review comprehensively examines the contributions of S100 proteins to the progression of these disorders, focusing on their potential as diagnostic and prognostic biomarkers, as well as therapeutic targets. S100A protein-mediated key molecular mechanisms that influence inflammation, airway remodeling, fibrosis, and tumorigenesis in the lungs are discussed. The importance of their normal function is evident from the observation that simultaneous mutations in S100A3 and S100A13 predispose individuals to early-onset pulmonary fibrosis, underscoring their critical role in lung health. Furthermore, sustained S100 protein elevation is explored in the context of long COVID, shedding light on its role in chronic inflammation. These proteins act as damage-associated molecular patterns (DAMPs), activating immune pathways via receptors like TLR4 and RAGE, thereby driving inflammation and immune cell recruitment. Notably, in lung transplantation, elevated levels of S100A8, S100A9, and S100A12 serve as early biomarkers of graft rejection and complications such as graft-vs.-host disease, which indicates their role in mediating immune responses and transplant outcomes. While promising, the clinical application of S100 proteins faces challenges, including disease-specific variability and the need for robust validation across diverse populations. This narrative review underscores the dual potential of S100 proteins as biomarkers and therapeutic targets in respiratory medicine while emphasizing the importance of overcoming current limitations through targeted research and clinical trials.},
}
@article {pmid41161981,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {643-655},
doi = {10.1016/j.cll.2025.07.008},
pmid = {41161981},
issn = {1557-9832},
mesh = {Humans ; *COVID-19/complications/prevention &amp; control ; *COVID-19 Vaccines/adverse effects ; *Hemostatic Disorders/etiology ; SARS-CoV-2 ; *Vaccination/adverse effects ; },
abstract = {The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.},
}
@article {pmid41161755,
year = {2025},
author = {Ozawa, T and Terai, H and Tanaka, H and Iba, A and Hosozawa, M and Hori, M and Muto, Y and Yoshida-Kohno, E and Namkoong, H and Chubachi, S and Takemura, R and Nagashima, K and Sato, Y and Ishii, M and Iso, H and Fukunaga, K and , },
title = {Japanese nationwide survey to track the impact of long COVID over 3 years.},
journal = {Environmental health and preventive medicine},
volume = {30},
number = {},
pages = {84},
pmid = {41161755},
issn = {1347-4715},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/epidemiology/economics/psychology/complications ; Japan/epidemiology ; *Post-Acute COVID-19 Syndrome/economics/epidemiology/psychology ; *Quality of Life ; Retrospective Studies ; Surveys and Questionnaires ; East Asian People ; },
abstract = {BACKGROUND: The long-term impact of symptom classification on quality of life (QOL) and economic outcomes among individuals with long coronavirus disease (COVID) remains poorly understood. This study aimed to clarify the situation of long COVID in Japan by analyzing patients using cluster classification.<br><br>METHODS: This multicenter, retrospective cohort study enrolled 515 patients with COVID-19 and followed up for 36 months via standardized questionnaires. Patients were classified based on: 1) symptom trajectory over time and 2) symptom cluster profiles at 3 months.<br><br>RESULTS: While the number of symptoms decreased, fatigue and dyspnea frequently persisted, whereas anosmia and dysgeusia declined. Cough and sputum decreased gradually. The proportion of patients with 5-9 symptoms increased. The mean (interquartile range) presenteeism scores were lower in the continuous (60 [50-80]) and relapse groups (65 [48-80]) than in the recovered group (70 [50-80]). The multiple symptoms cluster had the worst SF-36, presenteeism, and absenteeism scores (47.2 [44.7-49.8], 48.8 [27.5-72.5], and 10.9 [0.0-11.0], respectively).<br><br>CONCLUSIONS: Patients with continuous and multiple symptoms experienced persistently lower QOL and greater economic burden up to 36 months after COVID-19 diagnosis. The long-term effects of long COVID are not only physical but also mental and economical. Thus, further research is needed to clarify the economical and physiological impact of long COVID.},
}
@article {pmid41160239,
year = {2025},
author = {Krassnig, K and Bauer, R and Glasl, S and Haubenberger, P and Evanzin, HJ and Schneider, K and Margotti, D},
title = {[Herbal treatment options for post-viral symptoms and long COVID].},
journal = {Wiener medizinische Wochenschrift (1946)},
volume = {},
number = {},
pages = {},
pmid = {41160239},
issn = {1563-258X},
abstract = {BACKGROUND: Long COVID and post-viral symptom complexes have become a significant focus in medical practice. There is an urgent need to provide evidence-based treatment options to those patients. The aim of the literature review was to summarize herbal medicinal products as a treatment option for post-viral conditions, particularly long COVID.<br><br>METHODS: A&#xa0;working group of the Austrian Society for Phytotherapy conducted a&#xa0;narrative review between 2022 and 2024, based on external literature from the PubMed, PubPharm and Scopus databases and clinical experience from practice. The review identified the most relevant medicinal plants and their preparations for the most common symptom complexes of long COVID.<br><br>RESULTS: A&#xa0;total of 98&#xa0;publications and 24 monographs were included in the literature review. The symptom complexes (+ relevant phytopharmaceuticals) include neurological complaints, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Ginseng radix, Panax quinquefolii radix, Eleutherocci radix, Rhodiolae rhizoma et radix, Schisandrae fructus), nootropics (Ginkgo folium, Lavandulae flos), irritations of the respiratory tract (Liquiritiae radix, Nigellae semen, Eucalypti folium), gastrointestinal complaints (Gentianae radix, Centauri herba, Artemisii herba, Galangae rhizoma, Zingiberis rhizoma, Boswellia serrata, Curcuma longae rhizoma), circulatory weakness (Crataegi folium cum flore, Rosmarini folium, Salviae officinalis folium) and loss of smell (Rosae flos, Citri pericarpium, Caryophylli flos, Eucalypti folium). External evidence and clinical experience in medical practice show that many important symptoms of post-viral conditions can be successfully treated with herbal preparations.<br><br>CONCLUSION: Phytopharmaceuticals can provide evidence-based support for the therapeutic portfolio for viral diseases and their consequences in current and future viral epidemics.},
}
@article {pmid41159753,
year = {2025},
author = {Dette, A and Moers, F and Mayr, T and Stillfried, Sv and Bernhardt, M and Förster, S and Werlein, C and Ackermann, M and Muders, MH and Kristiansen, G and Boor, P and Gütgemann, I},
title = {Differential expression of viral entry protein neuropilin 1 (NRP1) and neuropilin 2 (NRP2) in fatal COVID-19.},
journal = {Journal of virology},
volume = {99},
number = {11},
pages = {e0138425},
pmid = {41159753},
issn = {1098-5514},
support = {01KX2524//National Autopsy Network/ ; O-115.0074//BONFOR/ ; //aTyr/ ; },
mesh = {Humans ; *Neuropilin-1/metabolism/genetics ; *Neuropilin-2/metabolism/genetics ; *COVID-19/metabolism/virology/pathology/mortality ; *SARS-CoV-2/physiology/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Lung/metabolism/virology/pathology ; Virus Internalization ; Male ; Female ; Angiotensin-Converting Enzyme 2/metabolism ; Endothelial Cells/metabolism/virology ; Aged ; Middle Aged ; Myocardium/metabolism ; },
abstract = {Coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, endothelialitis, hypoxemia, and hypercoagulation, contributing to thrombosis in acute severe and long COVID. While ACE2 is the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, its low expression in certain infected cell types suggests alternative co-receptors. Neuropilins (NRP1 and NRP2), widely expressed, have been proposed as co-factors for viral entry. We analyzed NRP1 and NRP2 expression in autopsy tissues from heart, lung, and hematolymphoid organs using immunohistochemistry (n = 20) and compared findings with public single-cell RNA sequencing (scRNAseq) data. Selected cases were further examined by spatial multiplex immunofluorescence (CODEX). In vitro binding of NRP1/NRP2 to SARS-CoV-2 spike fragments S1 and S1' was assessed by immunofluorescence microscopy. NRP1 was abundantly expressed in myocardial capillary endothelial cells (ECs) and macrophages in the heart and lung; NRP2 was found in alveolar macrophages and mast cells. scRNAseq re-analysis confirmed these in situ patterns. In vitro, NRP1 exclusively bound S1, while NRP2 bound both S1 and S1'. SARS-CoV-2 RNA was detected in neuropilin-positive, ACE2/TMPRSS2-negative vascular EC and mast cells. The detection of SARS-CoV-2 RNA in neuropilin-positive but ACE2/TMPRSS2-negative cell clusters supports that neuropilins are involved in systemic viral dissemination. NRP1 on vascular EC may contribute to angiogenesis, vascular damage, and microangiopathy, while NRP2 represents a potential immunomodulatory target to regulate macrophage activity, resolve inflammation, and potentially prevent the progression of pulmonary fibrosis and limit excessive mast cell activation in long COVID.IMPORTANCEThe well-known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), exhibits low expression in key cell types implicated in coronavirus disease 2019 (COVID-19) pathology, such as endothelial cells and B cells, macrophages, and mast cells. In contrast, neuropilins, identified as co-receptors for SARS-CoV-2, are abundantly expressed in these cells under physiological conditions and may be involved in virus-host interactions. This study presents a detailed in situ analysis of Neuropilin 1 (NRP1) and Neuropilin 2 (NRP2) expression in fatal COVID-19 cases using immunohistochemistry and spatial multiplex immunofluorescence phenotyping, complemented by single cell RNA sequencing. Additionally, it demonstrates differential binding affinities of NRP1 and NRP2 to SARS-CoV-2 spike protein fragments S1 and S1' in vitro, suggesting distinct roles for these neuropilins in viral recognition. This study highlights the impact of the unique furin cleavage site in SARS-CoV-2, which may contribute to increased pathogenicity through its interaction with NRP1.},
}
@article {pmid41159539,
year = {2025},
author = {Guzmán, V and Di Gravio, C and Cooper, E and Lound, A and Smith, N and O'Hara, M and Atchison, CJ and Cooke, G and Chadeau, M and Elliott, P and Ward, H},
title = {"I Put a Lot of Emphasis on Work Because I Want to Keep My Job": A Population-Based Interview Study of Long Covid and Employment Changes in England.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70476},
pmid = {41159539},
issn = {1369-7625},
support = {//This study is an independent research funded by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI): REACT-GE (UKRI MC_PC_20049) and REACT-LC (COV-LT-0040). The REACT-1 and REACT-2 studies were funded by the Department of Health and Social Care in England (DHSC). We also acknowledge support from the NIHR Imperial Biomedical Research Centre./ ; },
mesh = {Humans ; *COVID-19/psychology/complications ; England/epidemiology ; Male ; Female ; *Employment/psychology ; Middle Aged ; Qualitative Research ; Adult ; Interviews as Topic ; Adaptation, Psychological ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: Long Covid is a complex condition characterised by persistent multisystemic symptoms following a Covid-19 infection, which can influence an individual's capability to sustain employment. However, there is limited evidence of how diverse presentations of long Covid can shape employment and what support strategies might be useful for different groups.<br><br>AIM: To address this, we aimed to explore the experiences of employment changes among people living with long Covid in England and to identify the perceived barriers and enablers they face to cope with work.<br><br>DESIGN AND METHODS: We conducted a qualitative analysis of data from the Real-time Assessment of Community Transmission (REACT) Study. Using a framework analysis approach, we analysed 60 semi-structured interviews with people who experienced persistent Covid-19 symptoms for 12 weeks or more.<br><br>RESULTS: We identified three key themes: (1) Persistent Covid-19 symptoms at work; (2) Ripple effects of balancing work, identity and well-being with persistent Covid-19 symptoms; and (3) Employment changes to cope with and manage persistent Covid-19 symptoms. Participants identified multiple employment changes, including reduction of working hours, restructuring of roles and modification of responsibilities, and adapted ways of working. Drivers of employment changes included disruptive and fluctuating symptoms but also broader pandemic circumstances and the opportunities available for accessing organizational support and putting in place appropriate management strategies.<br><br>CONCLUSION: Our results provide a thorough understanding of the work changes experienced by people living with long Covid and highlight the need for intersectional, adaptable work accommodations to support their sustainable employment and overall well-being.<br><br>Members of the public who are part of a Public Advisory Group (PAG) have provided ongoing input into various aspects of the umbrella cohort study, the Real-time Assessment of Community Transmission (REACT) Study, including the study design, data collection instruments and dissemination of findings. For this qualitative study, which draws on interview data from REACT Long COVID (REACT-LC), preliminary findings were presented to the PAG for feedback and suggestions, which helped refine the discussion. Additionally, two Public Advisors with lived experience of long Covid contributed to the writing and editing of this manuscript. In accordance with these contributions, they are included as authors.},
}
@article {pmid41159191,
year = {2025},
author = {Huff, HV and Villanueva-Colina, C and Diaz, MM and Tovar, S and Davila Luna, A and Wu, T and Hamer, DH and Koralnik, IJ and Solomon, T and Caniza, MA and Garcia, PJ},
title = {Correction: Neurologic symptoms following COVID-19 in Lima, Peru: a prospective longitudinal observational study.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1676667},
doi = {10.3389/fneur.2025.1676667},
pmid = {41159191},
issn = {1664-2295},
support = {D43 TW010540/TW/FIC NIH HHS/United States ; },
abstract = {[This corrects the article DOI: 10.3389/fneur.2025.1524613.].},
}
@article {pmid41158347,
year = {2025},
author = {Xie, K and Zhang, P and Li, Y and Xia, L},
title = {The post-COVID-19 pulmonary sequelae: manifestations, mechanisms and treatment strategies.},
journal = {Journal of thoracic disease},
volume = {17},
number = {9},
pages = {7414-7429},
pmid = {41158347},
issn = {2072-1439},
abstract = {Recent studies have increasingly demonstrated that coronavirus disease 2019 (COVID-19) patients may develop long-term sequelae of varying severity, collectively referred to as long COVID or post-COVID-19 condition. Pulmonary sequelae are particularly common, which significantly impair patients' quality of life. The mechanisms underlying post-COVID-19 pulmonary sequelae are complex and multifactorial, and their management is still at an exploratory stage. This review explores the manifestations, underlying mechanisms, and potential treatment approaches for post-COVID-19 pulmonary sequelae. Fatigue, dyspnea, myalgia, and sleep disturbances are the most commonly reported symptoms following COVID-19 infection, while anxiety and depression are also prevalent. Respiratory symptoms include dyspnoea, persistent cough, hypoxia, and reduced exercise capacity. Impaired lung diffusion capacity is the most frequently observed pulmonary function abnormality, and residual abnormalities on chest computed tomography (CT) commonly include ground-glass opacities (GGO) and fibrotic-like changes. Air trapping is also an important CT finding and has been reported to associated with impaired lung diffusion function. The potential mechanisms may include pulmonary fibrosis, chronic inflammation, immune dysregulation, coagulation abnormalities and thrombosis, and persistent viral infection. Current treatment strategies encompass vaccination, pulmonary rehabilitation, and pharmacological interventions such as antifibrotic, anti-inflammatory, and anticoagulant therapies. A comprehensive understanding of the recovery trajectory and the mechanisms underlying post-COVID-19 pulmonary sequelae is crucial for improving patient outcomes.},
}
@article {pmid41157669,
year = {2025},
author = {Matyja-Bednarczyk, A and Dziedzic, R and Drynda, A and Gradzikiewicz, A and Bociąga-Jasik, M and Wójcik, K and Lichołai, S and Górka, K and Celejewska-Wójcik, N and Stachura, T and Polok, K and Zaręba, L and Iwaniec, T and Sładek, K and Bazan-Socha, S},
title = {Baseline Dysregulation in B, T, and NK Cells in COVID-19 Predicts Increased Late Mortality but Not Long-COVID Symptoms: Results from a Single-Center Observational Study.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
pmid = {41157669},
issn = {1999-4915},
support = {Jagiellonian University Medical College//N41/DBS/000687/ ; },
mesh = {Humans ; *COVID-19/mortality/immunology ; Male ; Female ; *Killer Cells, Natural/immunology ; Middle Aged ; Aged ; SARS-CoV-2/immunology ; *B-Lymphocytes/immunology ; *T-Lymphocytes/immunology ; Adult ; Poland/epidemiology ; Lymphocyte Count ; Severity of Illness Index ; Lymphopenia ; },
abstract = {The SARS-CoV-2 pandemic presents a broad clinical spectrum from asymptomatic cases to severe respiratory failure with high mortality. Severe COVID-19 is characterized by immune dysregulation, including lymphopenia and alterations in the counts of T, B, and NK cells in peripheral blood. Due to the limited data on long-term outcomes related to immune dysregulation, we aimed to analyze immunologic features at baseline in severe and mild COVID-19 cases and assess follow-up characteristics associated with later mortality and long-COVID signs. We included adult patients consecutively hospitalized with COVID-19 between June and November 2020 at the University Hospital in Kraków, corresponding to the first and second waves of COVID-19 in Poland. We enrolled only those who had been thoroughly assessed in terms of clinic and laboratory data, including immunological workups, and survived the acute phase of the disease. In 2025, between February and April (median time of follow-up: 54 months), we conducted a telephone questionnaire on long-COVID symptoms among survivors who had given their consent. Statistical analyses were performed to compare groups with severe and mild disease in terms of dysregulation in lymphocyte subpopulations and the follow-up outcomes. The study included 103 COVID-19 patients, comprising 53 severe (based on the need for at least high-flow nasal oxygen therapy) and 50 mild cases, with no differences in age, sex, and body mass index. Severe COVID-19 patients compared to mild cases had lower CD3+ T cells (count and percentage), CD4+ T cells (count and percentage), CD8+ T cells (count), and NK cells (count), but higher CD19+ B cells (percentage) at baseline (p < 0.05, all). At the time of follow-up, we evaluated 80 patients (77.7% of the baseline participants), with 23 (22.3%) patients lost to follow-up. Among patients analyzed in the follow-up, 23 (28.8%) had died, and 29 of the 57 survivors (50.9%) reported persistent long-COVID symptoms. Patients who died had significantly lower baseline counts of CD3+ T cells (377 vs. 655 cells/µL), CD4+ T cells (224 vs. 372 cells/µL), CD8+ T cells (113 vs. 188 cells/µL), and NK cells (118 vs. 157 cells/µL) compared to survivors (p < 0.05, all). Notably, the percentage of CD19+ B cells was higher in deceased individuals (19.2% vs. 13.5%; p = 0.049). In contrast, we did not document differences in baseline immunological data among survivors with and without long-COVID signs. Our study suggests that dysregulation in lymphocyte subpopulations during the COVID-19 acute phase may be associated with increased late mortality, but not with the persistence of long-COVID symptoms.},
}
@article {pmid41157587,
year = {2025},
author = {Heath, AM and Li, D},
title = {Symptomatology of Long COVID Associated with Inherited and Acquired Thrombophilic Conditions: A Systematic Review.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
pmid = {41157587},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications ; *Thrombophilia/complications ; SARS-CoV-2 ; },
abstract = {Thrombophilic conditions, conditions where blood has a tendency to form thrombi due to abnormal coagulatory processes, can affect the trajectory of diseases such as Post-Acute Sequelae of SARS-CoV-2 Infection, better known as Long COVID (LC), by worsening symptoms and complicating outlooks. As a comorbidity in pro-coagulatory diseases such as COVID-19 and LC, patients with thrombophilic conditions may experience worse symptoms than their peers, due to this elevated level of hypercoagulation. A 15-week literature review through the public PubMed database was conducted to investigate the severity, mechanisms, and symptom profiles of thrombophilic patients with LC. Papers were only included if samples included participants with pre-existing tendencies for hypercoagulable states, and confirmation of SARS-CoV-2 infection via a Polymerase Chain Reaction test. Each paper included in this review was analyzed by topic and assessed for eligibility against the Joanna Briggs Institute's Critical Appraisal tool. Each paper was also assessed for biases. Results from the 6 papers included in this review showed that LC could be predicted following COVID-19 illness by a hypercoagulable blood profile, indicating that LC may be linked to chronic hypercoagulation and inflammation post-infection. Additionally, symptoms linked to microthrombi formation, such as hair loss, arrhythmia, and dizziness, were exhibited more frequently in patients with thrombophilia and/or thrombophilic conditions, indicating that those with thrombophilic conditions may exhibit unique LC symptom profiles compared to healthy controls. This paper's research is preliminary and thus is limited in the strength of its findings; However, further research into LC and its interactions with co-morbidities like thrombophilic conditions would aid in the development of better treatment plans for patients, such as the usage of anticoagulants or screening for hypercoagulable blood profiles post-COVID-19 to assess patient risk.},
}
@article {pmid41157582,
year = {2025},
author = {Prakash, S and Karan, S and Lekbach, Y and Tifrea, DF and Figueroa, CJ and Ulmer, JB and Young, JF and Glenn, G and Gil, D and Jones, TM and Redfield, RR and BenMohamed, L},
title = {Insights into Persistent SARS-CoV-2 Reservoirs in Chronic Long COVID.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
pmid = {41157582},
issn = {1999-4915},
support = {R01 AI158060/AI/NIAID NIH HHS/United States ; AI158060//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/genetics ; Animals ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Disease Reservoirs/virology ; *Persistent Infection/virology ; },
abstract = {Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments ("brain fog"), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4[+] and CD8[+] T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC.},
}
@article {pmid41157565,
year = {2025},
author = {Lepojević-Stefanović, D and Živković, S and Marković, D and Marić, G and Marković-Nikolić, N},
title = {COVID-19 and Cardiovascular Complications: A Follow-Up Study from Tertiary Center.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
pmid = {41157565},
issn = {1999-4915},
support = {451-03-137/2025-03/200110//Ministry of Science, Technological Development and Innovation of the Republic of Serbia/ ; },
mesh = {Humans ; *COVID-19/complications/mortality/epidemiology ; Male ; Female ; *Cardiovascular Diseases/mortality/epidemiology/complications/etiology ; Tertiary Care Centers ; Middle Aged ; Aged ; Prospective Studies ; Follow-Up Studies ; Hospitalization ; SARS-CoV-2 ; Aged, 80 and over ; Adult ; },
abstract = {(1) Background: In addition to its fatal outcomes, COVID-19 is associated with a spectrum of non-fatal complications that significantly influence clinical trajectories and quality of life. Cardiovascular complications, in particular, are of major clinical relevance and are recognized as key contributors to both short- and long-term morbidity and mortality. The aim of the present study was to evaluate the short-term and long-term effects of COVID-19 infection on patients with underlying cardiovascular diseases. (2) Methods: The prospective cohort study included a total of 99 consecutive subjects hospitalized due to moderate and severe forms of COVID-19 pneumonia in "Zvezdara"-University Medical Center in the period of 18 March-18 April 2021. (3) Results: During hospitalization, 47% of patients had some new cardiovascular events. A total of 10 patients died during hospital stay. The highest chance for the lethal outcome was seen in those with previously diagnosed coronary heart disease (B = 3.356, OR = 28.667 (95% CI 2.69-305.14), p = 0.005), heart failure (B = 3.056, OR = 21.250 (95% CI 3.36-134.56), p = 0.001) and increased potassium values (B = 2.639, OR = 14.000 (95% CI 2.65-73.88), p = 0.002). (4) Conclusions: Care strategies for patients who survived the acute episode of COVID-19 should include attention to cardiovascular disease. Our findings emphasize the need for continued optimization of strategies for primary prevention of SARS-CoV-2 infections as the best way to prevent long COVID and serious cardiovascular complications.},
}
@article {pmid41157211,
year = {2025},
author = {Genova, S and Pencheva, M and Burnusuzov, H and Bozhkova, M and Kulinski, G and Kostyaneva, S and Tilkiyan, E and Abadjieva, T},
title = {High Free IgE and Mast Cell Activation in Long COVID: Mechanisms of Persistent Immune Dysregulation.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {10},
pages = {},
pmid = {41157211},
issn = {2075-1729},
abstract = {Background: Elevated serum IgE has been reported in severe COVID-19, suggesting that mast cell activation, allergic-like responses, and possible viral immune evasion occur. Objective: This study aimed to assess serum IgE, IgG, eosinophils, basophils, IL-10, and IL-33 in COVID-19 patients, and evaluate the infiltration of mast cells, basophils, and plasma cells in fatal cases. Methods: This retrospective study included 21 patients with severe COVID-19 or related respiratory conditions hospitalized in Plovdiv, Bulgaria (February 2020-May 2022). Serum immunoglobulins were quantified via immunoassays; IL-10 and IL-33 were also measured. Lung tissues from 30 autopsies were examined histologically and immunohistochemically using CD117 (mast cells) and CD138 (plasma cells). Results: Elevated IgE (>100 IU/mL) occurred in 10/21 patients, with two patients exhibiting levels exceeding 1000 IU/mL. High IgE correlated with reduced eosinophils and basophils, except in post-COVID lobar pneumonia. IL-10 was significantly increased, while IL-33 was reduced in acute and long COVID. Lung histology showed the accumulation of mast cells and plasma cells (5-20/field) during the diffuse alveolar damage and acute respiratory distress syndrome (ARDS) phases, but not in later fibrotic stages. Basophils are located near capillary basement membranes and the endothelium. Conclusions: SARS-CoV-2 may induce IgE-driven allergic-like mechanisms that contribute to severity. Monitoring IgE and mast cell activity may provide prognostic and therapeutic value, while elevated IgG4 could mitigate the effects of IgE.},
}
@article {pmid41157147,
year = {2025},
author = {Jach, ME and Sajnaga, E and Bumbul, M and Serefko, A and Borowicz, KK and Golczyk, H and Kieliszek, M and Wiater, A},
title = {The Role of Probiotics and Their Postbiotic Metabolites in Post-COVID-19 Syndrome.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {20},
pages = {},
pmid = {41157147},
issn = {1420-3049},
mesh = {*Probiotics/pharmacology/therapeutic use ; *Post-Acute COVID-19 Syndrome/complications/metabolism/therapy ; Humans ; Fatty Acids, Volatile/metabolism ; *SARS-CoV-2/drug effects/physiology ; Virus Replication/drug effects ; *Gastrointestinal Microbiome/drug effects/physiology ; Brain-Gut Axis/drug effects/physiology ; Neuropsychological Tests ; },
abstract = {Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut-brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies.},
}
@article {pmid41156656,
year = {2025},
author = {Delpino, MV and Quarleri, J},
title = {Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
pmid = {41156656},
issn = {2076-0817},
mesh = {Humans ; *Aging/metabolism ; *HIV Infections/metabolism/therapy/pathology ; *Mitochondria/metabolism/pathology ; *COVID-19/metabolism/therapy/pathology ; DNA, Mitochondrial/genetics ; *Mitochondrial Diseases/therapy ; Oxidative Stress ; SARS-CoV-2 ; Mitophagy ; },
abstract = {We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms-including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming-contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation.},
}
@article {pmid41156605,
year = {2025},
author = {Robinson, KF and Ahiya, AI and Richner, JM and Lutz, SE},
title = {SARS-CoV-2 Infection Influences Wnt/β-Catenin Pathway Components in Astrocytes.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
pmid = {41156605},
issn = {2076-0817},
support = {R56 NS138437/NS/NINDS NIH HHS/United States ; K12GM139186/GM/NIGMS NIH HHS/United States ; R01NS138437/NS/NINDS NIH HHS/United States ; K12 GM139186/GM/NIGMS NIH HHS/United States ; W81XWH-21-1-0893//Department of Defense/ ; 1R01NS135072-01A1/NS/NINDS NIH HHS/United States ; RF1 NS138437/NS/NINDS NIH HHS/United States ; },
mesh = {*Astrocytes/virology/metabolism ; *Wnt Signaling Pathway ; Humans ; *COVID-19/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *beta Catenin/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Wnt Proteins/metabolism/genetics ; Animals ; Cells, Cultured ; Mice ; },
abstract = {The mechanisms by which SARS-CoV-2 infection lead to neuroinflammation and cognitive impairment in COVID-19 and Long COVID are unclear. Cerebrovascular Wnt/β-catenin pathway activity is suppressed in association with neuroinflammation and cognitive impairment in a mouse model of COVID-19. In this study, we asked whether SARS-CoV-2 (NY Iota strain) infection of astrocytes would result in cell-autonomous changes in Wnt/β-catenin pathway components. We report that induced pluripotent stem cell (hiPSC)-derived human astrocytes (iAs) are susceptible to sustained infection with SARS-CoV-2 in vitro. Real-time PCR revealed that SARS-CoV-2 infection of iAs decreased transcripts for Wnt3a, Wnt10b, and the downstream pathway effectors β-catenin and TCF3. Wnt7b was increased, as was the proinflammatory chemokine CXCL10. No changes were noted in Wnt3, Wnt7a, TCF1, TCF4, or LEF1. These data indicate that SARS-CoV-2 infection differentially influences Wnt/β-catenin pathway components in astrocytes. These data could have implications for the mechanistic basis of COVID-19 and Long COVID.},
}
@article {pmid41156478,
year = {2025},
author = {Navarro-Cáceres, A and Gómez-Sánchez, L and Arroyo-Romero, S and Suárez-Moreno, N and Domínguez-Martín, A and Lugones-Sánchez, C and González-Sánchez, S and Rodríguez-Sánchez, E and García-Ortiz, L and Gómez-Sánchez, M and Navarro-Matias, E and Gómez-Marcos, MA},
title = {Relationship of Mediterranean Diet and Its Components with Parameters of Structure, Vascular Function, and Vascular Aging in Subjects Diagnosed with Long COVID: BioICOPER Study.},
journal = {Nutrients},
volume = {17},
number = {20},
pages = {},
pmid = {41156478},
issn = {2072-6643},
support = {PI21/00454//Instituto de Salud Carlos III (ISCIII/ ; RD21/0016/0010//Network for Research on Chronicity. Primary Care. and Health Promotion (RICAPPS)/ ; GRS 2501/B/22 and GRS2714/C/2023//The government of Castilla y Le&#xf3;n also collaborated with the funding of this study through the research projects/ ; PI21/00454//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; Male ; Female ; *Diet, Mediterranean ; Cross-Sectional Studies ; Middle Aged ; *COVID-19/physiopathology/complications ; Aged ; Carotid Intima-Media Thickness ; *Aging/physiology ; Pulse Wave Analysis ; Ankle Brachial Index ; SARS-CoV-2 ; Vascular Stiffness ; Adult ; Carotid-Femoral Pulse Wave Velocity ; Sex Factors ; },
abstract = {INTRODUCTION: Long COVID (LC) is associated with an increase in cardiovascular risk and chronic inflammation, whereas the Mediterranean Diet (MD) seems to improve the aforementioned factors. The aim of this study is to analyse the relationship between MD and its components with vascular structure, function, and aging in patients diagnosed with LC globally and by sex.<br><br>METHODS: This study was a cross-sectional study with 304 subjects diagnosed with LC; 207 were women and 97 men. Adherence to MD was evaluated with a validated MEDAS questionnaire, composed of 14 items. The vascular structure was assessed using carotid intima-media thickness (cIMT). Three measurements were carried out to evaluate vascular function: cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), and carotid-femoral pulse wave velocity (cfPWV). Vascular aging index (VAI) was estimated.<br><br>RESULTS: The MD score was 7.80 &#xb1; 2.33, with no difference between sexes. Vascular function and aging parameter values were higher in men than in women. Use of olive oil as the principal source of fat for cooking, and consuming <1 serving of butter/day and <1 sugar-sweetened beverage/day showed >90% adherence. Logistic regression analysis displayed associations between cIMT < 0.625 and use of olive oil in the global analysis (OR = 0.148) and among men (OR = 0.120), and <2 commercial pastries/week in global (OR = 0.536). cfPWV < 7.400 m/s was associated with DM score &#x2265; 8 in global (OR = 0.444) and in women, as well as with <2 pastries/week in women (OR = 0.405). baPWV < 12.315 m/s was associated with &#x2265;3 servings of pulses/week in global (OR = 0.481) and among women, as was <2 pastries/week in global (OR = 0.471) and in women. CAVI < 7.450 was associated with &#x2265;4 tablespoons of olive oil/day in men. VAI < 63.693 was associated with DM score &#x2265; 8 in global (OR = 0.458) and in women, as well as <2 pastries/week in global (OR = 0.392).<br><br>CONCLUSIONS: Adherence to MD was associated with lower cfPWV and VAI measures in the global analysis and among women. In particular, several of the components were associated with a better vascular profile in LC patients.},
}
@article {pmid41156093,
year = {2025},
author = {Mîțu, DA and Buleu, F and Popa, DI and Trebuian, C and Sutoi, D and Coman, A and Lighezan, DF and Buleu, T and Sliman, N and Radbea, OR and Mederle, OA},
title = {Outcomes, Sequelae, and Ventilatory Strategies in Long COVID Patients with Severe ARDS: A Retrospective Cohort Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {20},
pages = {},
pmid = {41156093},
issn = {2077-0383},
support = {Victor babes Univeristy of Medicine and Pharmacy, Timisoara//Victor babes Univeristy of Medicine and Pharmacy, Timisoara/ ; },
abstract = {Background and Aims: Severe acute respiratory distress syndrome (ARDS) in patients with long COVID remains associated with extremely high mortality and significant long-term sequelae. Non-invasive ventilatory strategies such as continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC) are widely used before endotracheal intubation (ETI). Still, their comparative effectiveness in this population is not well established. Understanding survival outcomes and sequelae can help refine treatment strategies for this high-risk group. This study aimed to evaluate outcomes, sequelae, and treatment strategies in long COVID patients with severe ARDS, focusing on non-invasive ventilatory support before ETI. Materials and Methods: A retrospective cohort analysis was performed using a study comparing severe ARDS patients with and without COVID-19. The inclusion criterion was a Horovitz quotient (PaO2/FiO2) < 50 mmHg. Results: The study included a total of 59 patients diagnosed with long COVID-19 ARDS, with a mortality rate of 85%. A significant proportion of the patient population was male, accounting for 75%. The highest survival rate was observed among patients who initially received CPAP support, with a survival rate of 23.08%, in contrast to those treated solely with HFNC or those who alternated between HFNC and CPAP. Among patients who required endotracheal intubation and subsequent mechanical ventilation, survival rates were 40% for those who had previously received CPAP, 10% for those treated with alternating HFNC and CPAP, and 0% for those managed exclusively with HFNC before ETI. Survivors often exhibited sequelae, such as impaired pulmonary function, persistent dyspnea, and diminished physical performance. Conclusions: Patients with long COVID who develop severe ARDS (PaO2/FiO2 < 50 mmHg) face exceptionally high ICU mortality, with outcomes determined mainly by age, comorbidities, and profound hypoxemia. Although CPAP showed a trend toward improved survival, the data do not establish superiority and should be regarded as hypothesis-generating. Rather, they highlight the complexity of managing this underrepresented subgroup and underscore the need for larger, multicenter studies with broader inclusion criteria to confirm or refute these preliminary observations.},
}
@article {pmid41155411,
year = {2025},
author = {Caliman-Sturdza, OA and Hamamah, S and Iatcu, OC and Lobiuc, A and Bosancu, A and Covasa, M},
title = {Microbiome and Long COVID-19: Current Evidence and Insights.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155411},
issn = {1422-0067},
support = {760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; 760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; },
mesh = {Humans ; *COVID-19/microbiology/complications ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Dysbiosis/microbiology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; *Microbiota ; },
abstract = {Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.},
}
@article {pmid41155393,
year = {2025},
author = {Mikheeva, EV and Aulova, KS and Nevinsky, GA and Timofeeva, AM},
title = {In Silico Analysis of MiRNA Regulatory Networks to Identify Potential Biomarkers for the Clinical Course of Viral Infections.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155393},
issn = {1422-0067},
support = {25-15-00010//Russian Science Foundation/ ; },
mesh = {*MicroRNAs/genetics ; Humans ; *Gene Regulatory Networks ; Biomarkers/metabolism ; *Virus Diseases/genetics ; Computer Simulation ; Computational Biology/methods ; Gene Expression Profiling ; Gene Expression Regulation ; },
abstract = {MiRNA expression profiles exhibit notable alterations in numerous diseases, particularly viral infections. Consequently, miRNAs may be regarded as both therapeutic targets and markers for the development of complications. MiRNAs can significantly influence the modulation of immune responses, offering an extra layer of regulation during viral infections. In this study, miRNAs associated with viral infections were analyzed using an in silico approach. Computer modeling predicted a number of miRNAs capable of influencing the functionality of specific components of the immune system. As a result, 242 miRNAs common to the three types of infections were identified. A network of miRNA-gene regulatory interactions, encompassing 502 nodes (224 miRNAs and 278 genes) and 2236 interactions, was developed. Within this network, subnetworks were identified that are involved in the operation of specific connections in the immune response to viruses. For each step of the immune response, the miRNAs involved in governing these processes were examined. These predicted miRNAs are of particular interest for further analysis aimed at establishing the relationship between their differential expression and disease symptom severity. The obtained data lay the foundation for identifying the most promising molecules as predictive biomarkers and the subsequent development of a diagnostic system.},
}
@article {pmid41155179,
year = {2025},
author = {Refrigeri, M and Tola, A and Mogavero, R and Pietracupa, MM and Gionta, G and Scatena, R},
title = {Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155179},
issn = {1422-0067},
mesh = {Humans ; *Mitochondria/metabolism/virology/pathology ; *COVID-19/metabolism/virology/pathology ; *SARS-CoV-2/metabolism/pathogenicity ; Reactive Oxygen Species/metabolism ; Host-Pathogen Interactions ; Immunity, Innate ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus-host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology.},
}
@article {pmid41154289,
year = {2025},
author = {Wilson, A and Ricciardiello Mejia, GC and Lomba, S and Geng, LN and Malunjkar, S and Bonilla, H and Sum-Ping, O},
title = {A Multidimensional Assessment of Sleep Disorders in Long COVID Using the Alliance Sleep Questionnaire.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {20},
pages = {},
pmid = {41154289},
issn = {2227-9032},
abstract = {Background/Objectives: Sleep disturbances are recognized as a common feature of Long COVID but detailed investigation into the specific nature of these sleep symptoms remain limited. This study analyzes comprehensive sleep questionnaire data from a Long COVID clinic to better characterize the nature and prevalence of sleep complaints in this population. Methods: We conducted a cross-sectional analysis of 200 adults referred to the Stanford Long COVID Clinic. Patients completed an intake questionnaire including three sleep-related items (unrefreshing sleep, insomnia, daytime sleepiness) rated on a 0-5 Likert scale. Additionally, patients completed the Alliance Sleep Questionnaire (ASQ), incorporating the Insomnia Severity Index, Epworth Sleepiness Scale, reduced Morningness-Eveningness Questionnaire, and modules for parasomnia, restless legs, and breathing symptoms. We calculated the prevalence of six sleep symptom domains. Standardized symptom data were analyzed using principal component analysis (PCA) and K-means clustering (k = 2) to explore latent phenotypes and used logistic regression to assess associations between demographic and clinical variables and each sleep complaint. Results: Sleep-related breathing complaints affected 57.5% of participants, insomnia 42.5%, and excessive daytime sleepiness 28.5%. Parallel analysis supported a nine-factor structure explaining ~90% of variance, with varimax rotation yielding interpretable domains such as insomnia/unrefreshing sleep, fatigue/post-exertional malaise, parasomnias, and respiratory symptoms. Gaussian mixture modeling favored a two-cluster solution (n = 94 and n = 106); one cluster represented a higher-burden phenotype characterized by greater BMI, insomnia, daytime sleepiness, gastrointestinal symptoms, and parasomnias. Logistic models using factor scores predicted insomnia with high accuracy (AUC = 0.90), EDS moderately well (AUC = 0.81), but extreme chronotype poorly (AUC = 0.39). In adjusted models, hospitalization during acute COVID-19 was significantly associated with insomnia (OR 4.41; 95% CI 1.27-15.36). Participants identifying as multiracial had higher odds of insomnia (OR 3.22; 95% CI 1.00-10.34), though this narrowly missed statistical significance. No other predictors were significant. Conclusions: Sleep disturbances are frequent and diverse in Long COVID. Factor analysis showed overlapping domains, while clustering identified a higher-burden phenotype marked by more severe sleep and systemic complaints. Symptom-based screening may help target those at greatest risk.},
}
@article {pmid41151241,
year = {2025},
author = {Raijmakers, RPH and Lund Berven, L and Keijmel, SP and Rodrigo, C and Wyller, VBB and Katz, BZ and Buchwald, D and Evans, RA and Gérardin, P and Knoop, H and Prins, M and Stavem, K and Stiansen-Sonerud, T and Taylor, R and Valencia Arroyo, BM and Wensaas, KA and Selvakumar, JP and van den Wijngaard, C and Lloyd, AR and Sandler, CX},
title = {Immunological associations in post-infective fatigue syndromes including Long COVID-a systematic review and meta-analysis.},
journal = {EBioMedicine},
volume = {121},
number = {},
pages = {105970},
pmid = {41151241},
issn = {2352-3964},
support = {R01 AI105781/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/complications/immunology ; SARS-CoV-2 ; Biomarkers ; *Fatigue/immunology/etiology ; },
abstract = {BACKGROUND: The pathophysiology of post-infective fatigue syndromes (PIFS), including Long COVID, is unknown. This systematic review and meta-analysis aimed to investigate if PIFS is associated with persistent immune activation.<br><br>METHODS: PubMed, EMBASE, and Web of Science were searched for terms related to infection, fatigue, persistent symptoms, and immunological markers.<br><br>POPULATION: adults and adolescents; Exposure: documented acute infection; Comparator: those who developed PIFS vs. recovered controls from the same exposure; and Outcomes: immunological biomarkers. Studies which documented acute infection, applied diagnostic criteria for PIFS, and assayed circulating immunologic markers were eligible.<br><br>FINDINGS: From 14,985 studies screened, 30 articles were included (n = 5102 participants; 833 PIFS/PIFS-like cases, n = 4269 recovered control participants) with many studies excluded by inadequate quality in eligibility criteria. The meta-analysis (11 studies; n = 413 PIFS cases, analysed with random-effects models) showed PIFS cases had increased: white cell counts at 3-6 months (Cohen's d: 0.41, 95% CI 0.09-0.74); and circulating levels of RANTES and TNF&#x3b1; at 6-12 months (Cohen's d: 0.45 [95% CI 0.16-0.73] and 0.30 [95% CI 0.04-0.57], respectively) compared to controls recovered from the same exposure.<br><br>INTERPRETATION: These findings provide cautious support for persistent immune activation in PIFS, but warrant further replication. Future studies should include better documentation of acute infection and PIFS case characterisation.<br><br>FUNDING: ARL is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant 1041897). CXS is supported by a Cancer Institute New South Wales Early Career Fellowship (2021/ECF1310). BZK is supported by the National Institute of Allergy and Infectious Diseases (AI 105781). RAE is supported by the National Institute for Health and Care.},
}
@article {pmid41149071,
year = {2025},
author = {Mazzanti, S and Barchiesi, F and Pallotta, F and Luchetti, I and Giacometti, A and Brescini, L},
title = {Severe Acute SARS-CoV-2 Infection and Long COVID: What Do We Know So Far? New Challenges in Diagnosis and Management.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {10},
pages = {},
pmid = {41149071},
issn = {2079-9721},
abstract = {BACKGROUND/OBJECTIVES: The long-term impact of the COVID-19 pandemic is not just limited to socioeconomic aspects; there are also important health issues to consider. Among these, one of the most important and obvious is long COVID. Despite a significant amount of scientific work having been published, this condition is still semi-unknown. The objective of this study was to collect useful information for the clarification of some epidemiological, clinical, and laboratory characteristics of this disease.<br><br>METHODS: This was a single-center study carried out at the Infectious Diseases Clinic of the hospital "AUO delle Marche" on all patients hospitalized for COVID-19 between November 2021 and March 2022.<br><br>RESULTS: From the data, it emerged that, following the resolution of the acute phase of SARS-CoV-2 infection, the majority of people experienced health problems that persisted for at least 6 months. The manifestations and outcomes affect different systems; therefore, long COVID, like COVID-19, has systemic involvement and the clinical manifestations may be residues of the damage caused by the disease during the acute phase, or new manifestations whose pathogenesis is still a matter of discussion.<br><br>CONCLUSIONS: The persistence of inflammation and the dysregulation of the immune system represent some of the pathogenetic hypotheses. Inflammation could therefore represent one of the physiopathogenetic mechanisms of long COVID, and it is possible that it is responsible for the clinical symptoms that appear in the months following the resolution of the acute phase of the disease.},
}
@article {pmid41148083,
year = {2026},
author = {Floridia, M and Pagnanelli, G and Piccinni, G and Weimer, LE and Onder, G and , },
title = {Persisting or recurrent dermatological manifestations in Long-COVID: Data from a national cohort of 1741 patients from Italy.},
journal = {Journal of the American Academy of Dermatology},
volume = {94},
number = {2},
pages = {637-641},
doi = {10.1016/j.jaad.2025.10.024},
pmid = {41148083},
issn = {1097-6787},
}
@article {pmid41146907,
year = {2025},
author = {Padhye, AS and Koralnik, IJ and Hanson, BA and Visvabharathy, L and DeLisle, RK and Tachas, G},
title = {Blood diagnostic biomarkers for neurologic manifestations of long COVID.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {49},
number = {},
pages = {101110},
pmid = {41146907},
issn = {2666-3546},
abstract = {BACKGROUND: SARS-CoV-2 responsible for COVID-19 caused a global pandemic, with billions of infections, millions of deaths and ongoing manifestations post COVID-19. "Long Covid", a Post-Acute Sequelae of COVID-19 (PASC), is an ongoing global healthcare problem, affecting all age groups, with many manifestations, and occurring despite vaccines and antivirals. Neurologic manifestations of PASC (Neuro-PASC) such as brain fog can last for years and are amongst the most debilitating and prevalent. There is a need for diagnostic tools and treatments.<br><br>METHODS: Plasma samples from 48 non-hospitalized PASC patients with diagnosed Neuro-PASC symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7000 proteins using the SomaLogic&#xae; proteomics platform. ProViz&#xae; software was used to perform T-tests, U-Tests, ANOVA and Kruskalis-Wallis tests at a Bonferroni p&#xa0;<&#xa0;0.05 and a Benjamini-Hochberg corrected False Discovery Rate <0.02, and box plots and knowhow used to identify diagnostic biomarkers and therapeutic targets.<br><br>RESULTS: C5a, TGF&#x3b2;1, and Gliomedin, used together differentiated patients with Neuro-PASC from control subjects with 94&#xa0;% sensitivity and 86&#xa0;% specificity, a 90&#xa0;% accuracy. Additional biomarkers, Gal3ST1, IFN&#x3bb;1, and GHRH, improved accuracy to 94&#xa0;%, and a combination of 5 more biomarkers, LFA-3, FASLG&#xa0;+&#xa0;Transgelin-1 and GPNMB&#xa0;+&#xa0;IGHG1, improved accuracy close to 100&#xa0;%. These markers are suggestive of pathways involved in Neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs.<br><br>CONCLUSION: C5a, TGF&#x3b2;1, Gliomedin expressed highly in serum could be developed as a diagnostic tool, and with clinical assessment used to personalize treatments with repurposed novel drugs.},
}
@article {pmid41146789,
year = {2025},
author = {Dudek, A and Bursy, M and Szkudlarek, W and Linkiewicz, J and Fabiszewski, Z and Starosta, P},
title = {Chronic Cardiovascular Disorders Associated With COVID-19: A Literature Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93271},
pmid = {41146789},
issn = {2168-8184},
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is now widely recognized for causing several long-term effects known as post-COVID-19 syndrome (PCS) or long COVID (LC). This presents a growing challenge for healthcare systems worldwide. This narrative review summarizes original peer-reviewed studies indexed in PubMed and published between January 2020 and August 2025. It focuses on adult populations unless stated otherwise. We included studies that provided primary clinical or imaging data on chronic cardiovascular outcomes after confirmed SARS-CoV-2 infection. We excluded case reports, pediatric-only cohorts, and non-peer-reviewed sources. Among the various cardiovascular issues related to LC, we focused on heart fibrosis (HF), postural orthostatic tachycardia syndrome (POTS), new-onset hypertension (HT), and coagulopathy. These conditions consistently show up in the reports and are significant in terms of illness, potential long-term disability, and public health impact. Although these issues are distinct in their underlying causes, they share common mechanisms. These include ongoing inflammation of the endothelium, disruption of the renin-angiotensin-aldosterone system (RAAS), immune-related tissue damage, and an ongoing state that promotes blood clots. These processes can lead to measurable myocardial fibrosis that cardiac magnetic resonance imaging can detect, autonomic dysfunction often seen as POTS, a greater risk of developing hypertension shortly after infection, and a long-term rise in thromboembolic events due to increased clotting and resistant microclots. Current management is mostly focused on relief of symptoms and involves a team approach. It uses repurposed medications and tailored physical rehabilitation since no specific cure is available yet. Promising but still experimental methods, such as endothelial-protective agents like sulodexide and targeting inflammatory pathways, need thorough testing. There are significant gaps in our understanding of the long-term risk of hypertension, the natural progression of fibrosis, and the best treatment for POTS. This highlights urgent needs for future research. Beyond caring for individual patients, these ongoing cardiovascular problems raise important public health concerns. They include higher healthcare use, long-term disability, and economic costs. This situation requires increased clinical attention and proactive cardiovascular monitoring for those recovering from COVID-19.},
}
@article {pmid41146089,
year = {2025},
author = {Blay, N and Farré, X and Garcia-Aymerich, J and Castaño-Vinyals, G and Kogevinas, M and de Cid, R},
title = {Pre-pandemic disease trajectories and genetic insights into long COVID susceptibility.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {590},
pmid = {41146089},
issn = {1741-7015},
support = {TED2021-130626B-I00//Ministerio de Ciencia e Innovaci&#xf3;n/ ; SR20-01024//'la Caixa' Foundation/ ; 167/C/2021//Fundaci&#xf3; la Marat&#xf3; de TV3/ ; PI18/01512//Ministerio de Sanidad, Consumo y Bienestar/ ; GA:101046314//HORIZON EUROPE Health/ ; },
mesh = {Humans ; Female ; *COVID-19/genetics/epidemiology ; Middle Aged ; Male ; Adult ; *Genetic Predisposition to Disease ; Aged ; SARS-CoV-2 ; Comorbidity ; Chronic Disease/epidemiology ; Multifactorial Inheritance ; Risk Factors ; Cohort Studies ; },
abstract = {BACKGROUND: Long COVID refers to the persistence of symptoms after SARS-CoV-2 infection. While individual comorbidities have been studied, the role of coexisting chronic conditions remains underexplored. This study investigates whether pre-pandemic disease trajectories-sequential patterns of chronic conditions-modify long COVID risk and symptom profiles and explores shared genetic susceptibility.<br><br>METHODS: We analysed 8322 adult participants (58.6% women) from the COVICAT cohort (aged 40-65 at recruitment), followed between 2020 and 2023. Disease trajectories were reconstructed from electronic health records (2010-2019), focusing on sequences of two chronic conditions found in&#x2009;&#x2265;&#x2009;1% of the cohort. We evaluated shared genetic architecture and polygenic risk scores (PRS) for predictive capacity.<br><br>RESULTS: Thirty-eight disease trajectories were associated with increased long COVID risk. These trajectories primarily involved mental and neurological disorders (e.g. depression, anxiety, migraine), respiratory diseases (e.g. asthma, allergic rhinitis) and cardiometabolic or digestive conditions (e.g. hypertension, lipidaemia, obesity, gastroesophageal reflux). No significant genetic correlations with long COVID were detected, but polygenic risk scores for two nervous system and musculoskeletal conditions showed modest associations with increased risk.<br><br>CONCLUSIONS: Disease trajectories were significantly associated with long COVID, with a sex effect, highlighting the importance of pre-pandemic disease trajectories. While no strong overall genetic correlations were found, modest polygenic associations suggest a role for shared susceptibility in nervous system and musculoskeletal disorders. From a public health perspective, identifying high-risk multimorbid individuals may inform targeted prevention and care strategies.},
}
@article {pmid41145523,
year = {2025},
author = {Martins Conde, P and Bulaev, D and Rauschenberger, A and Ohnmacht, J and Fritz, JV and O'Sullivan, MP and Ancien, F and Ghosh, S and Tsurkalenko, O and Kolodkin, A and Satagopam, V and Vaillant, M and Klucken, J and Krüger, R and , },
title = {Co-occurrence of memory impairment and fatigue distinguishes post COVID from pandemic-related health effects in the 4-year CON-VINCE cohort study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37381},
pmid = {41145523},
issn = {2045-2322},
support = {FNR 14716281/CON-VINCE/Kruger//Fonds National de la Recherche Luxembourg/ ; 101016167//European Commission/ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology/psychology ; Female ; *Fatigue/epidemiology/etiology/diagnosis ; Male ; *Memory Disorders/epidemiology/etiology/diagnosis ; Middle Aged ; Adult ; SARS-CoV-2/isolation &amp; purification ; Aged ; Risk Factors ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Luxembourg/epidemiology ; Pandemics ; Anxiety/epidemiology ; Depression/epidemiology ; Cohort Studies ; Comorbidity ; },
abstract = {A major challenge in diagnosing post COVID lies in differentiating symptoms following a confirmed SARS-CoV-2 infection from those that may also occur in uninfected individuals (post COVID mimics) and be associated with a broader impact of the pandemic. The WHO post COVID definition was applied to the Luxembourgish longitudinal CON-VINCE cohort, where SARS-CoV-2 infection was confirmed via either a positive RT-qPCR or a serology test. Risk factor analysis was conducted on 1,865 individuals. Female gender, lower resilience, greater loneliness, and a higher number of comorbidities were associated with symptoms persistence. The symptomatology and comorbidity profiles of 559 participants (including 50 post COVID and 66 post COVID mimics) were investigated. Two distinct clusters of persistent symptoms were identified: (1) depression with anxiety, present in both infected and non-infected groups, and (2) memory impairment with fatigue, unique to the post COVID group. Therefore, presence of both memory impairment and fatigue may help differentiate post COVID patients from post COVID mimics. Yet, verification that memory impairment was newly developed was not possible, as this symptom was not recorded at baseline. Our findings suggest that future studies should consider factors affecting development of persistent post COVID-like symptoms observed in individuals that were never infected.},
}
@article {pmid41145456,
year = {2025},
author = {Sujith, S and Gatzke, N},
title = {An overview of clinical presentation and management of long COVID.},
journal = {The Nurse practitioner},
volume = {50},
number = {11},
pages = {38-42},
doi = {10.1097/01.NPR.0000000000000374},
pmid = {41145456},
issn = {1538-8662},
mesh = {Humans ; *COVID-19/nursing/complications/therapy ; Risk Factors ; Nurse Practitioners ; SARS-CoV-2 ; },
abstract = {The COVID-19 pandemic has been the 21st century's most significant public health emergency. In addition to the acute symptoms of COVID-19, many individuals are facing long-term health issues related to the infection. The terms "long COVID," "postacute sequelae of SARS-CoV-2 infection," "postacute COVID syndrome," and "long-haul COVID-19" refer to long-term consequences of SARS-CoV-2 infection. Symptoms may persist for weeks or months, reducing quality of life. Health practitioners must stay updated and take proactive measures to manage long COVID effectively. This manuscript provides an overview of risk factors, diagnostic tools, and management strategies, which serve as a resource for understanding and managing long COVID.},
}
@article {pmid41144164,
year = {2025},
author = {Colaneri, M and Galbussera, AA and Tettamanti, M and Puoti, M and Marchetti, G and Piva, S and Plebani, P and Raviglione, M and Gori, A and Bandera, A and Nobili, A},
title = {Specialist Healthcare Intervention and Follow-up Trends in Post-Acute COVID-19 Hospitalization as Compared to Other Respiratory Infections.},
journal = {Infectious diseases and therapy},
volume = {14},
number = {12},
pages = {2869-2884},
pmid = {41144164},
issn = {2193-8229},
support = {2021-4236//Fondazione Cariplo/ ; },
abstract = {INTRODUCTION: Post-acute sequelae of COVID-19, often referred to as "long COVID," have raised concerns about increased healthcare utilization following hospitalization. Whether these patterns differ significantly from those observed after other acute respiratory infections (ARIs) remains unclear. This study aimed to compare post-discharge healthcare use between patients hospitalized for COVID-19 and those with other ARIs in Lombardy, Italy.<br><br>METHODS: We conducted a population-based cohort study using 2021 administrative healthcare data from the Lombardy Region. Patients aged&#x2009;&#x2265;&#x2009;40&#xa0;years hospitalized for COVID-19 or other ARIs were followed for 12&#xa0;months post-discharge. We evaluated specialist consultations, rehospitalizations, diagnostic testing, and new chronic drug treatment initiations. Logistic regression models adjusted for age, sex, and comorbidities (Drug-Derived Complexity Index) were used to assess differences.<br><br>RESULTS: Among 57,795 patients, 35,458 were hospitalized for COVID-19 and 21,375 for other ARIs. Patients with COVID-19 were younger and had lower comorbidity burden and post-discharge mortality (10.7% vs. 33.5%). A higher proportion received at least one specialist visit (75.8% vs. 70.3%), though with a longer median time to first visit (63 vs. 45&#xa0;days, p&#x2009;<&#x2009;0.0001). Patients with COVID-19&#xa0;had more frequent imaging and spirometry but initiated fewer chronic drug treatments overall. However, a higher prescription rate for antidiabetics (OR 1.42), psychoanaleptic (OR 1.21), and genitourinary/hormonal drugs (OR 1.29) emerged after COVID-19&#xa0;hospitalizations: this rate remained statistically higher for antidiabetics even after excluding subjects who died in the year following discharge. Hospitalizations for causes other than COVID-19 were more frequent in patients with ARI.<br><br>CONCLUSIONS: Compared to other ARIs, COVID-19 survivors exhibited distinct post-discharge healthcare patterns, with delayed but focused specialist care and selective increases in diagnostic and pharmacological interventions.},
}
@article {pmid41143594,
year = {2025},
author = {Wehrli, S and Hartner, AM and Boender, TS and Arnrich, B and Irrgang, C},
title = {Information Pathways and Voids in Critical German Online Communities During the COVID-19 Vaccination Discourse: Cross-Platform and Mixed Methods Analysis.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e76309},
pmid = {41143594},
issn = {1438-8871},
mesh = {Germany/epidemiology ; Humans ; *COVID-19/prevention &amp; control/epidemiology ; SARS-CoV-2 ; *COVID-19 Vaccines ; *Social Media ; Pandemics ; Public Health ; *Vaccination ; },
abstract = {BACKGROUND: In Germany, the messaging app Telegram (Telegram FZ-LLC) served as a tool to organize protests against public health measures during the COVID-19 pandemic. A community of diverse groups formed around these protests, which used Telegram to discuss and share views outside of the general public discourse and mainstream information ecosystem. This increasingly included conspiracy theories and extremist content, propagated by sources that opposed the mainstream positions of the government and traditional media. While the use of such sources has been thoroughly investigated, the role of mainstream information in these communities remains largely unclear.<br><br>OBJECTIVE: We aimed to better understand the use of mainstream information, that is, from government actors and established media outlets, within critical Telegram communities in the context of the COVID-19 pandemic in Germany. We focused on the discourse about the COVID-19 vaccination, a key public health measure. As a central element of this study, we compared the Telegram discourse with the discourse on X (formerly Twitter, X Corp) and in online news-this cross-platform analysis aimed to put the results into a broader societal context.<br><br>METHODS: We analyzed Telegram, X, and news data between 2019 and 2023 for popular topics related to the COVID-19 vaccination discourse. We used a mixed methods approach, including text clustering for the exploration of popular topics, a 2-stage keyword filtering scheme for multitopic classification, link sharing analysis for assessing the prevalence of mainstream information, correlation-based time series analysis for measuring the similarity of discourse dynamics, and thematic analysis to examine the reasons for sharing information.<br><br>RESULTS: We identified 5 popular vaccination-related topics that were discussed on both Telegram and X, namely death, long COVID, measures in schools, mandatory vaccination, and virus variants. On average per topic, 58% (SD 5.2%) of Telegram posts and 21% (SD 4.9%) of X posts contained an external link. Of these posts containing external links, 11%-35% of Telegram posts and 44%-60% of X posts contained a mainstream link per topic. The correlations for week-to-week changes in discourse intensity between Telegram, X, and online mainstream news ranged from no positive association (coefficient <0.2) to strong positive relationships (coefficient >0.6) per topic. Finally, the thematic analysis resulted in 5 themes describing the usage patterns of mainstream information on Telegram and X. The identified themes are observing news, news comments, directed accusations, participation, and reference in discussion (only X).<br><br>CONCLUSIONS: Mainstream information sources were part of the information mix within the analyzed critical Telegram communities. However, the role and prevalence of these sources varied. We argue that differences between platforms may indicate the existence of information voids, which pose a particular challenge in managing infodemics. These insights emphasize the importance of contextualized cross-platform analyses for understanding complex information pathways and their potential for targeted crisis communication.},
}
@article {pmid41142667,
year = {2025},
author = {Hirschtick, JL and Slocum, E and Whittington, B and Elliott, MR and Ahmed, S and Fleischer, NL},
title = {Comparison of survey questions to define long COVID: Implications for prevalence and disparities.},
journal = {Preventive medicine reports},
volume = {59},
number = {},
pages = {103269},
pmid = {41142667},
issn = {2211-3355},
abstract = {OBJECTIVE: To understand whether variation in survey-based Long COVID estimates is partially due to how and when survey questions are asked.<br><br>METHODS: We compared Long COVID prevalence using distinct questions within a population-based, longitudinal survey of adults with confirmed SARS-CoV-2 before June 2022 in Michigan.<br><br>RESULTS: In our sample (n&#xa0;=&#xa0;3826), 17.0&#xa0;% reported symptoms for 90+ days at baseline, a median of 4.4&#xa0;months after COVID-19 onset. A median of 18.4&#xa0;months after COVID-19 onset, 24.5&#xa0;% reported ever experiencing Long COVID, 16.9&#xa0;% reported current Long COVID, and 10.8&#xa0;% reported diagnosed Long COVID. Among adults without 90-day symptoms at baseline, 17.3&#xa0;% reported ever Long COVID at follow-up. Relatedly, among adults with 90-day symptoms at baseline, 31.1&#xa0;% reported they never had Long COVID at follow-up. After adjustment for reinfection, respondents who were Hispanic (vs. White) or lower income (<$75,000 vs. $75,000+) had greater odds of reporting baseline symptoms but never experiencing Long COVID at follow-up. Conversely, Black (vs. White) respondents had greater odds of reporting ever Long COVID at follow-up without baseline symptoms.<br><br>CONCLUSION: Surveys should employ several questions to define Long COVID and interpret findings within the context of factors likely contributing to discrepancies, including reinfection, stigma, awareness, and care-seeking behaviors.},
}
@article {pmid41142132,
year = {2025},
author = {Kitsios, GD and Li, K and Blacka, S and Fitch, A and Jacobs, J and Naqvi, A and Zhang, B and Gentry, H and Murray, C and Wang, X and Patel, A and Puzniak, L and Rudolph, A and Dai, F and Mellors, J and Sciurba, F and Methe, B and Nouraie, SM and Morris, A},
title = {Oral and gut microbiota relate to symptom subphenotypes in long COVID, independent of viral persistence.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113628},
pmid = {41142132},
issn = {2589-0042},
abstract = {Long COVID presents a significant public health challenge, complicating diagnosis and treatment. In a prospective study of 349 individuals with long COVID (March 2021-December 2023), latent class analysis identified three symptom subphenotypes: high constitutional symptom burden (21%), predominant smell/taste disturbances (17%), and minimal persisting symptoms (62%). While viral persistence in saliva and stool was limited, 16S rRNA gene sequencing revealed microbiota associations with symptomatology. Alpha diversity was lower in individuals with high symptom burden, and specific taxa correlated with nausea and smell/taste disturbances. Distinct oral and gut microbiota patterns emerged across symptom clusters, with microbiota profiles also linked to patient-reported outcomes, including employment and overall health impact. These findings suggest that bacterial dysbiosis may contribute to long COVID symptom variability and highlight the microbiome's potential role in its pathophysiology. Understanding microbial influences on symptom persistence may inform microbiome-targeted therapeutic strategies and improve long COVID management.},
}
@article {pmid41141591,
year = {2025},
author = {An, H and Yu, T and Wang, A and Hu, H and Zhang, C and Wang, Y and Li, M},
title = {Persistent lymphocytopenia in convalescent patients with COVID-19: dysregulated B cell, CD4[+] T cell, and treg compartments in 7-12% of moderate-severe cases.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1693743},
pmid = {41141591},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/complications/pathology ; *Lymphopenia/immunology ; Male ; Female ; Middle Aged ; *B-Lymphocytes/immunology ; *CD4-Positive T-Lymphocytes/immunology ; *T-Lymphocytes, Regulatory/immunology ; Longitudinal Studies ; Convalescence ; SARS-CoV-2/immunology ; Adult ; Aged ; Lymphocyte Count ; Severity of Illness Index ; },
abstract = {BACKGROUND: Long COVID manifests with heterogeneous clinical outcomes, potentially linked to immune dysfunction. However, the recovery of immune-cell subsets during convalescence remains incompletely understood.<br><br>METHODS: In this longitudinal cohort, 279 unvaccinated patients with confirmed SARS-CoV-2 infection (13 mild, 218 moderate, 48 severe) were enrolled. Peripheral lymphocyte subsets were analyzed by flow cytometry at admission and at 50 days post-symptom onset (DPSO 50).<br><br>RESULTS: Total T-cell counts normalized in 90-98% of patients in the moderate and severe groups by DPSO 50. Nevertheless, a subgroup exhibited persistent B-cell lymphopenia (<90 cells/&#xb5;L) in 7.3% of moderate cases (median 77.1 cells/&#xb5;L, IQR 51.9-83.8) and 12.5% of seltvere cases (median 54.5 cells/&#xb5;L, IQR 28.4-79.3). Patients with B-cell deficiency also showed concurrent reductions in total T cells, CD4[+] T cells, and CD4[+]CD25[+]CD127low/FOXP3[+] regulatory T cells (Tregs). In moderate cases, CD4[+] T cell and Treg counts correlated positively (r = 0.72, p < 0.001), independent of B-cell status, whereas this relationship was absent in severe cases, indicating severity-dependent immune dysregulation.<br><br>CONCLUSIONS: Approximately 7-12% of moderate-to-severe COVID-19 survivors displayed persistent lymphopenia affecting B cells, CD4[+] T cells, and Tregs at ~50 days post-symptom onset. These findings highlight distinct recovery trajectories and provide insights into Long COVID pathogenesis that may inform therapeutic strategies.},
}
@article {pmid41140967,
year = {2025},
author = {Haq, AM},
title = {Comment on "Pre-pandemic diabetes and risk of long COVID: Longitudinal evidence".},
journal = {Journal of diabetes and metabolic disorders},
volume = {24},
number = {2},
pages = {245},
pmid = {41140967},
issn = {2251-6581},
}
@article {pmid41140205,
year = {2025},
author = {McCready, JL and Campbell, M and McCay, K and Moore, J and Deary, V and Vines, J and Higgs-McCallum, C and Webster, D and Ellis, J and Newton, J and Nobbs, C and Rapley, T and Hackett, KL},
title = {Optimising and beta-testing a user-centred, accessible, self-management rehabilitation smartphone app (reCOVer) for long-COVID fatigue using qualitative interview methods.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/09638288.2025.2577872},
pmid = {41140205},
issn = {1464-5165},
abstract = {PURPOSE: Fatigue is one of the most common and disabling symptoms of long-COVID, yet individuals often struggle to access appropriate services and must self-manage. This study aimed to adapt an existing smartphone app, originally developed for fatigue in autoimmune rheumatic disease, for individuals with long-COVID.<br><br>MATERIALS AND METHODS: A multidisciplinary steering group reviewed current clinical and scientific evidence to inform the adaptation of the app, reCOVer. The app includes an activity pacing diary, goal-setting tool, assertiveness and communication cards, and guidance on fatigue, sleep, relaxation, and setbacks. Beta-testing was conducted with 11 individuals with long-COVID (aged 21-57). Each participant took part in two serial qualitative interviews: the first explored their experience of fatigue and initial reactions to the app; the second, after 7-10&#x2009;days of use, captured usability and acceptability feedback.<br><br>RESULTS: Participants found reCOVer helpful, particularly for increasing awareness of unhelpful patterns (e.g., boom-bust cycles) and supporting behaviour change through pacing. Communication tools were valuable when cognitive difficulties were prominent. Suggested improvements included text-to-speech functionality, clearer goal-setting instructions, and better articulation of app benefits.<br><br>CONCLUSIONS: reCOVer shows promise as a self-management tool for long-COVID fatigue. Further research, such as a pilot RCT, is needed to evaluate feasibility and effectiveness.},
}
@article {pmid41138821,
year = {2025},
author = {Sano, K and Kimura, Y and Hirahata, K and Kato, H and Hasegawa, H and Akutsu, H and Ryo, A and Goto, A and Miyakawa, K},
title = {SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID.},
journal = {The Journal of infection},
volume = {91},
number = {5},
pages = {106641},
doi = {10.1016/j.jinf.2025.106641},
pmid = {41138821},
issn = {1532-2742},
}
@article {pmid41138585,
year = {2025},
author = {Feter, N and Caputo, EL and Silveira da Silva, L and Cunha, L and Delpino, FM and de Almeida Paz, I and Cozzensa da Silva, M and Schröeder, N and Feter, J and Reichert, FF and Rombaldi, AJ},
title = {Long-term consequences of mental health distress during the COVID-19 pandemic on subjective memory decline: findings of the PAMPA cohort.},
journal = {Public health},
volume = {249},
number = {},
pages = {105974},
doi = {10.1016/j.puhe.2025.105974},
pmid = {41138585},
issn = {1476-5616},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; Middle Aged ; Brazil/epidemiology ; *Memory Disorders/epidemiology/psychology ; *Anxiety/epidemiology ; Adult ; Prospective Studies ; *Depression/epidemiology ; Longitudinal Studies ; Aged ; Mental Health ; Pandemics ; },
abstract = {OBJECTIVES: While the acute impact of COVID-19 on mental health has been documented, less is known about its long-term consequences on cognitive health. We investigated the association between worsening depressive and anxiety symptoms during the pandemic with the risk of subjective memory decline over a three-year follow-up.<br><br>STUDY DESIGN: Prospective cohort study.<br><br>METHODS: We analyzed data from 682 adults participating in the PAMPA cohort, a longitudinal study in southern Brazil. Changes in depressive and anxiety symptoms were assessed at baseline (2020) and during the pre-pandemic period retrospectively. Subjective memory decline was self-reported in the fourth follow-up (2023). Robust Poisson regression was used to estimate associations. Inverse probability weighting was used to estimate selection bias.<br><br>RESULTS: Over follow-up, 51&#xa0;% (95&#xa0;%CI: 47.1&#xa0;%-54.6&#xa0;%) of participants reported subjective memory decline. Worsened depressive (RR: 1.33; 95&#xa0;%CI: 1.21-1.64) and anxiety (RR: 1.36; 95&#xa0;%CI: 1.28-1.44) symptoms were associated with a higher risk of subjective memory decline. Each one-point increase in depression (RR&#xa0;=&#xa0;1.04; 95&#xa0;% CI: 1.03-1.05) and anxiety (RR&#xa0;=&#xa0;1.02; 95&#xa0;% CI: 1.01-1.03) symptoms was linked to a 4.3&#xa0;% and 2.4&#xa0;% increase in the risk of subjective memory decline. Associations remained robust after adjusting for COVID-19 status and other potential confounders, including depressive and anxiety symptoms at follow-up. Results were consistent in sensitivity analyses excluding participants with long COVID.<br><br>CONCLUSION: Worsening mental health during the COVID-19 pandemic predicted subjective memory decline three years later. Our findings underscore the importance of mental health support as a public health strategy to preserve long-term cognitive function, particularly after large-scale crises.},
}
@article {pmid41138391,
year = {2025},
author = {Badhwar, S and Pereira, TJ and Kerr, K and Bray, R and Tabassum, F and Sergio, L and Edgell, H},
title = {Autonomic phenotyping, brain blood flow control, and cognitive-motor-integration in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.},
journal = {Autonomic neuroscience : basic &amp; clinical},
volume = {262},
number = {},
pages = {103358},
doi = {10.1016/j.autneu.2025.103358},
pmid = {41138391},
issn = {1872-7484},
mesh = {Humans ; *COVID-19/physiopathology/complications ; *Fatigue Syndrome, Chronic/physiopathology ; Male ; Pilot Projects ; Female ; Adult ; Middle Aged ; *Cerebrovascular Circulation/physiology ; Phenotype ; *Cognition/physiology ; *Autonomic Nervous System/physiopathology ; Hemodynamics/physiology ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the prolonged sequelae after COVID-19 (>3 months; Long COVID) have similar symptomology, are both associated with autonomic dysfunction, and a growing proportion of Long COVID patients are developing ME/CFS. We aimed to determine an autonomic phenotype of patients with ME/CFS vs Long COVID. We hypothesized that the groups would differ from controls yet be similar to one another. We recruited sedentary controls (n = 10), mild/moderate ME/CFS patients (n = 12), and Long COVID patients (n = 9) to undergo 1) breathing 5 % CO2, 2) breathing 10 % O2, and 3) 5-minutes of 70° head-up tilt. Respiratory, hemodynamic, and cerebrovascular variables were measured throughout the 3 trials. Resting vascular function and cognitive-motor-integration were also assessed. ME/CFS and Long COVID were similar to the healthy controls and each other with regard to resting vascular function and the hemodynamic responses to hypoxia, hypercapnia, and head-up tilt (p > 0.05). However, in ME/CFS we observed a greater reduction of cerebrovascular resistance (p = 0.041) and impaired autoregulation (p = 0.042) during hypercapnia alongside impaired cognitive-motor integration (p < 0.02), and in Long COVID we observed reduced peripheral and end-tidal oxygen (p < 0.04) and less vagal withdrawal during tilt (p = 0.028). Our findings suggest unique phenotypes when comparing ME/CFS and Long COVID whereby we have shown that Long COVID patients experience hypoxia while upright contributing to less vagal withdrawal, and ME/CFS patients experience impaired cerebrovascular control during hypercapnia potentially leading to reduced cognitive-motor integration. These differences could stem from disease severity/duration or some unique aspect of the COVID-19 virus.},
}
@article {pmid41138036,
year = {2025},
author = {Yamamoto, K and Inoue, T and Ikeda, T and Sawai, T and Nagayoshi, Y and Hashiguchi, K and Futsuki, Y and Matsubara, Y and Harada, Y and Ashizawa, N and Fukahori, S and Iwanaga, N and Takazono, T and Kido, T and Ishimoto, H and Hosogaya, N and Sakamoto, N and Tashiro, M and Tanaka, T and Fukushima, C and Jounai, K and Tsuji, R and Fujiwara, D and Ota, K and Kosai, K and Furumoto, A and Yanagihara, K and Izumikawa, K and Mukae, H},
title = {Efficacy of Lactococcus lactis Strain Plasma in Patients with Mild COVID-19: A Multicenter, Double-Blinded, Randomized-Controlled Trial (PLATEAU Study).},
journal = {Infectious diseases and therapy},
volume = {14},
number = {12},
pages = {2835-2851},
pmid = {41138036},
issn = {2193-8229},
support = {H21003539//Kirin Holdings Co., Ltd./ ; },
abstract = {INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still an ongoing public health threat. COVID-19 can be accompanied by prolonged symptoms, known as "long COVID", however, no pharmaceutical treatments are currently available for these symptoms. Lactococcus lactis strain Plasma (LC-Plasma; Lactococcus lactis subsp. lactis JCM 5805) directly activates human plasmacytoid dendritic cells (pDCs) and triggers antiviral immune responses. We hypothesized that LC-Plasma reduced SARS-CoV-2 viral load and eased symptoms in patients with mild COVID-19.<br><br>METHODS: This PLATEAU study enrolled 100 patients with mild COVID-19 during Omicron BA.1 endemic, who were randomized into the LC-Plasma or placebo group in a 1:1 ratio and were observed for 14&#xa0;days. The primary endpoint was change in total score of eight subjective symptoms (fatigue, anorexia, headache, cough, shortness of breath, chest pain, smell, and taste disturbance). Secondary endpoints included each symptom, SARS-CoV-2 viral load, and pDCs.<br><br>RESULTS: The primary endpoint did not show between-group differences. However, the proportion of patients without smell and taste disturbances was significantly higher in the LC-Plasma group on day 13 (p&#xa0;=&#xa0;0.030). The LC-Plasma group showed a significantly earlier decrease in SARS-CoV-2 viral load on day 4 (p&#xa0;<&#xa0;0.001) and an increase in pDCs on day 8 (p&#xa0;=&#xa0;0.0498). Mild adverse events, such as diarrhea, cough-variant asthma, and urticaria, occurred in three (5.9%) patients in the LC-Plasma group.<br><br>CONCLUSIONS: The intake of LC-Plasma in patients with mild COVID-19 activates pDC, decreases SARS-CoV-2 viral load earlier, and may improve smell and taste disorders more quickly. LC-Plasma could be a safe, inexpensive, and easily accessible tool for the treatment of mild COVID-19.<br><br>TRIAL REGISTRATION: jRCTs071210097.},
}
@article {pmid41136644,
year = {2025},
author = {Miller, AJ and Wei, G and Stoddard, GJ and Jeyapalina, S and Agarwal, JP},
title = {Pre-existing comorbidities and hospitalization for COVID-19 are associated with post-COVID conditions in the U.S. veteran population.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {442},
pmid = {41136644},
issn = {2730-664X},
support = {UM1 TR004409/TR/NCATS NIH HHS/United States ; UM1TR004409//U.S. Department of Health &amp; Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; CO-US-983-6072//Gilead Sciences (Gilead)/ ; },
abstract = {INTRODUCTION: Although most survivors of COVID-19 return to their baseline health within two weeks, a notable proportion of individuals continue experiencing symptoms, collectively referred to as Post-COVID Conditions (PCC). To better understand risks associated with contracting PCC, this study aimed to determine whether association exists between pre-existing comorbidities, hospitalization for COVID-19 and the subsequent diagnosis of PCC in US veterans.<br><br>METHODS: This retrospective cohort study collected data from the US Department of Veterans Affairs electronic medical records from September 1, 2021, to July 31, 2023. Participants were limited to those with electronic medical records of a SARS-CoV-2 infection, who received care from the Veterans Affairs hospital system and survived at least 28 days following the infection.<br><br>RESULTS: The multivariable logistic regression analysis reveals in hospitalized veterans, chronic obstructive pulmonary disease (COPD) associates with a 21% increase in odds of a PCC diagnosis (adjusted OR 1.21, 95%CI 1.14-1.29; p&#x2009;<&#x2009;0.001), while in non-hospitalized veterans, chronic kidney disease (OR 1.09 95%CI 1.03-1.15; p&#x2009;=&#x2009;0.001)) and COPD (OR 1.33, 95%CI 1.27-1.40; p&#x2009;<&#x2009;0.001) demonstrate an increase in odds of a PCC diagnosis. Additionally, unvaccinated and partially vaccinated veterans exhibit significantly higher odds for PCC (p&#x2009;<&#x2009;0.001) compared to fully vaccinated veterans in both the hospitalized and non-hospitalized cohorts. Increasing age, increasing BMI, female sex, Hispanic ethnicity, and veterans residing in the Southwestern United States show a significant (p&#x2009;<&#x2009;0.05) increase in risk for a positive diagnosis of PCC in both groups.<br><br>CONCLUSIONS: Veterans with pre-existing COPD or those hospitalized at the time of COVID-19 (indicating disease severity) are at higher risk of receiving a PCC diagnosis.},
}
@article {pmid41136524,
year = {2025},
author = {Georgopoulos, AP and James, LM and Peterson, PK},
title = {HLA and pathogens in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other post-infection conditions.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37303},
pmid = {41136524},
issn = {2045-2322},
mesh = {Humans ; *Fatigue Syndrome, Chronic/virology/immunology/genetics ; Alleles ; *HLA Antigens/genetics/immunology/metabolism ; Antigens, Viral/immunology/metabolism ; Genetic Predisposition to Disease ; *Herpesviridae/immunology ; COVID-19/virology/immunology ; SARS-CoV-2/immunology ; },
abstract = {Viral infections have been widely implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) pathogenesis. Recent evidence has also identified certain Human Leukocyte Antigen (HLA) alleles that are significantly associated with ME/CFS risk/protection. Here we tested the hypothesis that ME/CFS risk or protection conferred from those HLA alleles is associated with binding affinity to antigens of HHV viruses, a critical step in initiating the adaptive immune system response to foreign antigens. Specifically, we determined in silico the predicted binding affinity of two susceptibility alleles (C*07:04, DQB1*03:03) and two protective alleles (B*08:01, DPB1*02:01) to > 10,000 antigens of the 9 Human Herpes Viruses (HHV1, HHV2, HHV3, HHV4, HHV5, HHV6A, HHV6B, HHV7, HHV8) which have been implicated in the etiology of ME/CFS. We found that the binding affinity of all HHV antigens to the susceptibility alleles was significantly weaker than the binding affinity to the protective alleles (P < 0.001). In fact, none of the HHV antigens showed strong binding to the susceptibility alleles, in contrast to the strong bindings showed by the protective alleles. These findings are in keeping with the hypothesis that the effect of a putative HHV insult in contributing to ME/CFS is modulated by the host's HLA immunogenetic makeup. We speculate that strong HLA-antigen binding likely protects against ME/CFS via elimination of virus antigens; conversely, weak HLA-antigen binding may permit persistence of foreign antigens, contributing to ME/CFS and other chronic conditions. Finally, with respect to the latter, we determined the binding affinities to the 4 HLA alleles above to pathogens causing two chronic diseases with very similar symptomatology to ME/CFS, namely Long COVID and post-treatment Lyme disease syndrome (PTLDS). We found that the 2 ME/CFS susceptibility HLA alleles above had very weak binding with SARS-CoV-2 virus glycoprotein (involved in Long COVID) and 5 proteins of Borrelia burgdorferi (involved in PTLDS), in contrast to the ME/CFS protective alleles that showed strong bindings. These findings support the hypothesis that ME/CFS, long COVID and PTLDS are caused by persistent pathogenic antigens that could not be eliminated due to inadequate protection by the patient's HLA makeup.},
}
@article {pmid41135584,
year = {2025},
author = {Botdorf, M and Dickinson, K and Lorman, V and Razzaghi, H and Marchesani, N and Rao, S and Rogerson, C and Higginbotham, M and Mejias, A and Salyakina, D and Thacker, D and Dandachi, D and Christakis, DA and Taylor, E and Schwenk, HT and Morizono, H and Cogen, JD and Pajor, NM and Jhaveri, R and Forrest, CB and Bailey, LC and , },
title = {Identifying Pediatric Long COVID: Comparing an EHR Algorithm to Manual Review.},
journal = {Applied clinical informatics},
volume = {16},
number = {5},
pages = {1445-1456},
pmid = {41135584},
issn = {1869-0327},
support = {OT2HL161847-01//NIH Researching COVID to Enhance Recovery (RECOVER) Initiative/ ; },
mesh = {Humans ; *Electronic Health Records ; *COVID-19/diagnosis/epidemiology ; Child ; Female ; *Algorithms ; Male ; SARS-CoV-2 ; Child, Preschool ; Adolescent ; },
abstract = {Long COVID, characterized by persistent or recurring symptoms post-COVID-19 infection, poses challenges for pediatric care and research due to the lack of a standardized clinical definition. Adult-focused phenotypes do not translate well to children, given developmental and physiological differences, and pediatric-specific phenotypes have not been compared with chart review.This study introduces and evaluates a pediatric-specific rule-based computable phenotype (CP) to identify long COVID using electronic health record data. We compare its performance to manual chart review.We applied the CP, composed of diagnostic codes empirically associated with long COVID, to 339,467 pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The CP identified 31,781 patients with long COVID. Clinicians conducted chart reviews on a subset of patients across 16 hospital systems to assess performance. We qualitatively reviewed discordant cases to understand differences between CP and clinician identification.Among the 651 reviewed patients (339 females, M age = 10.10 years), the CP showed moderate agreement with clinician identification (accuracy = 0.62, positive predictive value [PPV] = 0.49, negative predictive value [NPV] = 0.75, sensitivity = 0.52, specificity = 0.84). Performance was largely consistent across age and dominant variant but varied by symptom cluster count. Most discrepancies between the CP and chart review occurred when the CP identified a case, but the clinician did not, often because clinicians attributed symptoms to preexisting conditions (73%). When clinicians identified cases missed by the CP, they often used broader symptom or timing criteria (69%). Model performance improved when the CP accounted for preexisting conditions (accuracy = 0.71, PPV = 0.65, NPV = 0.74, sensitivity = 0.59, specificity = 0.79).This study presents a CP for pediatric long COVID. While agreement with manual review was moderate, most discrepancies were explained by differences in interpreting symptoms when patients had preexisting conditions. Accounting for these conditions improved accuracy and highlights the need for a consensus definition. These findings support the development of reliable, scalable tools for pediatric long COVID research.},
}
@article {pmid41135020,
year = {2025},
author = {Andrassy, B and Tallada, S and Harris, M and Mukhdomi, T},
title = {Stellate Ganglion Block for Headache Pain and Cognitive Impairment Associated With Long COVID Persisting Over 12 Months: A Case Report.},
journal = {Pain medicine case reports},
volume = {9},
number = {6},
pages = {305-309},
pmid = {41135020},
issn = {2768-5152},
mesh = {Humans ; Female ; *Stellate Ganglion ; *Autonomic Nerve Block/methods ; Middle Aged ; *Cognitive Dysfunction/etiology/therapy ; *COVID-19/complications ; *Headache/etiology/therapy ; Bupivacaine ; Anesthetics, Local ; },
abstract = {BACKGROUND: Postacute sequelae of COVID-19 (PASC) are debilitating health conditions affecting over 7% of the US population. Clinical PASC manifestations are variable, but consistently involve dysautonomia and elevated inflammatory biomarkers. Common symptoms include pain, fatigue, cognitive impairment, sensory loss, and orthostatic intolerance. As neuroimmune hyperactivation and reductions in cerebral blood flow are each implicated in PASC pathophysiology, stellate ganglion block (SGB) represents a promising treatment option due to its ability to reset autonomic activity and reperfuse the brain. We sought to retrospectively assess the potential of SGB to treat head and neck pain, cognitive impairment, and fatigue associated with PASC persisting over 12 months.<br><br>CASE REPORT: We reviewed and analyzed case data from 2 middle-aged female patients with painful, longstanding PASC managed with repeat unilateral SGB. Procedures were performed under ultrasound guidance, with 3 mL 0.5% bupivacaine + 12 mg betamethasone as the injectate. Each patient received 2 SGBs, with all procedures being tolerated well. No complications occurred. One patient had a recurrence of migraine pain following the blocks, while the other experienced durable relief. Both patients saw improvements in cognitive function and fatigue postoperatively, which were sustained.<br><br>CONCLUSIONS: Most literature on SGB for PASC management concerns its ability to reverse sensory loss, rather than relieve chronic pain. This case report provides preliminary evidence supporting the effectiveness of SGB for managing pain and cognitive impairment in PASC. As PASC symptoms with longer durations tend to be less effectively managed with SGB, we speculate that chronicity of the patients' symptoms hampered SGB-mediated pain relief.},
}
@article {pmid41134786,
year = {2025},
author = {Durstenfeld, MS and Mataraarachchi, N and Peluso, MJ and Levkova-Clark, M and Schaffer, V and Fehrman, EA and Anderson, G and Flores, D and Henrich, TJ and Long, CS and Deeks, SG and Hsue, PY},
title = {Case-control study of autonomic symptoms in the setting of Long COVID with tilt table testing.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0335218},
pmid = {41134786},
issn = {1932-6203},
mesh = {Humans ; Female ; *Tilt-Table Test ; Middle Aged ; Male ; *COVID-19/complications/physiopathology ; Heart Rate/physiology ; Aged ; Case-Control Studies ; Adult ; SARS-CoV-2 ; *Autonomic Nervous System/physiopathology ; Blood Pressure/physiology ; Post-Acute COVID-19 Syndrome ; *Autonomic Nervous System Diseases/physiopathology/diagnosis ; Hypotension, Orthostatic/physiopathology/diagnosis ; },
abstract = {BACKGROUND: Autonomic symptoms and orthostatic syndromes have been reported in Long COVID, but few studies have characterized findings using head up tilt table testing.<br><br>OBJECTIVE: To characterize autonomic responses to positional changes among individuals with Long COVID.<br><br>METHODS: We assessed autonomic symptoms using the Composite Autonomic Symptom Scale 31 (COMPASS 31) instrument and performed head up tilt table testing for 30 minutes at 70&#x2009;degrees among individuals with Long COVID and recovered comparators.<br><br>RESULTS: We included 26 participants (median age 56 years, 50% female median 25 months after first COVID): 16 with Long COVID and 10 recovered comparators. COMPASS 31 scores (0-100, higher is worse) were higher among those with Long COVID (median 30.5 vs 8, p&#x2009;=&#x2009;0.003). Heart rate was 8 beats per minutes higher throughout tilt among those with Long COVID (95% CI 1.1 to 14.4; p&#x2009;=&#x2009;0.02); there were no differences in blood pressure. Ten (63%) with Long COVID had symptoms during tilt compared to none among recovered participants (p&#x2009;=&#x2009;0.003). Three (19%) with Long COVID had clinically abnormal findings: one each with orthostatic hypotension, and delayed orthostatic hypotension, and cardioinhibitory/vasovagal presyncope.<br><br>CONCLUSIONS: Among those with chronic autonomic symptoms in the setting of Long COVID, symptoms were common during tilt testing, and heart rate was increased, but most did not meet diagnostic criteria for a clinically abnormal hemodynamic response. Further research into mechanisms of autonomic symptoms in Long COVID is urgently needed.},
}
@article {pmid41134747,
year = {2025},
author = {Algera, E and Maukner, AC and van Dorth, J and Alblas, MC and Sobel, J and de Vries, DH},
title = {'I Do Take the Number Seriously, but I Don't Let My Moods Depend on It': Negotiating Self-Tracking Data With People Living With Long COVID in the Netherlands, Austria and Switzerland.},
journal = {Sociology of health &amp; illness},
volume = {47},
number = {8},
pages = {e70102},
pmid = {41134747},
issn = {1467-9566},
support = {ISIDORe / grant agreement 101046133//HORIZON EUROPE Research Infrastructures/ ; },
mesh = {Humans ; Netherlands ; Switzerland/epidemiology ; *COVID-19/psychology ; Austria ; Male ; Female ; Middle Aged ; Interviews as Topic ; Aged ; Qualitative Research ; SARS-CoV-2 ; Adult ; Negotiating ; },
abstract = {For many people living with long COVID (PWLC), self-tracking has emerged as a valuable practice to monitor their illness. An examination of self-tracking practices can, therefore, shed light on the ways in which individuals navigate their care, make sense of their experiences and advocate for their needs. This study investigates how PWLC engage in self-tracking practices and how they utilise and negotiate the data generated. Based on 33 semi-structured interviews with PWLC in the Netherlands, Austria and Switzerland, we found that PWLC use self-tracking to recognise patterns and identify limits, triggers and effective interventions. The insights drawn from this are used to make informed decisions about health management strategies. Yet, self-tracking may also reify symptoms and negatively influence the subjective illness experience, exacerbating stress and anxiety. Although PWLC themselves negotiate and question their tracking data, they find a variety of responses from healthcare providers in clinical interactions. Using the concept of 'trading zone' (Kjærulff and Langstrup), we argue that although self-tracking cannot replace treatment and good care, its integration into the healthcare experience as a valuable form of patient knowledge may improve the patient-provider relationship.},
}
@article {pmid41134583,
year = {2025},
author = {Abbasi, J},
title = {New Guidance on Cardiovascular Disease and COVID-19-From Infection to Long COVID to Vaccination.},
journal = {JAMA},
volume = {334},
number = {20},
pages = {1786-1788},
doi = {10.1001/jama.2025.18834},
pmid = {41134583},
issn = {1538-3598},
}
@article {pmid41132887,
year = {2025},
author = {Vernon, SD and Rond, C and Sun, Y and Roundy, S and Bell, J and Rond, B and Kaufman, DL and Cash, AB and Yellman, B and Bateman, L},
title = {Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1691147},
pmid = {41132887},
issn = {1664-2295},
abstract = {BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by fatigue, cognitive impairment, and reduced physical function. Oxaloacetate (OAA), a metabolic compound with potential mitochondrial and neuroprotective effects, has shown promise in reducing fatigue symptoms in ME/CFS. However, the interrelationships between fatigue, cognitive performance, and physical activity and their responsiveness to treatment remain poorly understood in ME/CFS.<br><br>METHODS: This 90-day randomized, double-blind, controlled trial evaluated the effects of 2,000&#x202f;mg/day OAA or a control of 2,000&#x202f;mg rice flour in 82 adults with ME/CFS. Self-reported fatigue (Chalder Fatigue Questionnaire), cognitive function (DANA Brain Vital), and upright activity time (UP Time) were assessed at baseline and three follow-up visits. Linear mixed-effects models examined associations between fatigue severity and cognitive/physical function, with treatment group interactions. Responder status at the last visit (Visit 4) was classified based on &#x2265;15% fatigue reduction and/or &#x2265;10% cognitive improvement.<br><br>RESULTS: The OAA group showed greater cognitive improvement over time, with a significant between-group difference at Visit 3, 60&#x202f;days into the trial, (p&#x202f;=&#x202f;0.034) and trends at other visits. Higher fatigue was significantly associated with reduced cognitive gains in the OAA group (&#x3b2;&#x202f;=&#x202f;-0.34, p&#x202f;<&#x202f;0.0001), but not in controls. UP Time increased modestly in the OAA group, reaching significance at Visit 2, day 30 (p&#x202f;=&#x202f;0.044), though fatigue was not a strong predictor of UP Time in either group. At Visit 4, day 90, Global and Fatigue Only Responders were more frequent in the OAA group, while Cognitive Only Responders were more frequent in controls, though group differences did not reach statistical significance (p&#x202f;=&#x202f;0.10).<br><br>CONCLUSION: OAA supplementation was associated with improved cognitive performance and small improvement in UP Time in ME/CFS participants receiving OAA. Fatigue-cognition coupling was particularly strong in OAA-treated participants, suggesting a potentially targetable phenotype. These findings underscore the importance of multidimensional outcome measures in ME/CFS clinical trials and support the need for more research and trials of metabolic interventions in ME/CFS.},
}
@article {pmid41132394,
year = {2025},
author = {Sawyer, A and Preston, R and Leeming, H and Martin-Fuller, L and Proal, A and Putrino, D},
title = {Wearable technology in the management of complex chronic illness: preliminary survey results on self-reported outcomes.},
journal = {Frontiers in digital health},
volume = {7},
number = {},
pages = {1662255},
pmid = {41132394},
issn = {2673-253X},
abstract = {INTRODUCTION: Complex chronic illnesses like Long Covid (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are marked by fluctuating symptoms, often exacerbated by physical, cognitive, or emotional exertion in a phenomenon known as post-exertional malaise (PEM). Home monitoring technologies offer potential benefits by enabling individuals to track symptoms and biometrics, aiding in disease self-management. However, the general effectiveness of such tools is still unknown.<br><br>METHODS: A random sample of users of the Visible mobile application (Visible Plus; requires both the armband and paid subscription), aged 18 or older and with self-identified complex chronic illnesses such as LC or ME/CFS, were invited to complete an online survey regarding the impact of the app on their chronic disease self-management. Descriptive statistics related to the responses were analyzed and reported.<br><br>RESULTS: The survey was distributed to 2,636 people, with 1,301 participants responding (49.3% response rate). The average age was 46 years. 82% of respondents were female, 8% were male, 8% were non-binary, and 2% preferred not to say or preferred to self-describe. Participants self-identified as having ME/CFS only (n&#x2009;=&#x2009;534, 42%), LC only (n&#x2009;=&#x2009;396, 31%), ME/CFS and LC (n&#x2009;=&#x2009;236, 18%), or another illness (n&#x2009;=&#x2009;122, 10%). Of the n&#x2009;=&#x2009;2,636 randomly selected subscribers, the mostly commonly listed "other illnesses" were Postural Orthostatic Tachycardia Syndrome (POTS, 6%), fibromyalgia (5.2%), Ehlers Danlos Syndrome (EDS; 1.7%) and Mast Cell Activation Syndrome (MCAS, 1.2%). Of those with at least 30 days of data, 77% reported seeing an improvements associated with app use, corresponding to 23% of all invited users, 85% (corresponding to 29% of all invited users) reported feeling somewhat (53%) or significantly (32%), and 94% (corresponding to 33% of all invited users) reported a better understanding of their energy budget.<br><br>DISCUSSION: Home-monitoring based mobile applications are feasible and acceptable for a motivated subgroup of people with energy-limiting complex chronic illnesses, and are associated with self-reported benefits in energy management and participation in daily activities. The findings of this study should be interpreted as descriptive and hypothesis-generating and do not represent clinically significant effects, underscoring the need for randomized controlled trials to formally evaluate efficacy. Future studies should incorporate a comparison group to better differentiate intervention effects from improvements gained through lived experience.},
}
@article {pmid41132192,
year = {2025},
author = {Lo, M and Eiriksson, L and Hunter, S and Twomey, R and Skolnik, K and Chen, J and Afshar, EE and Weatherald, J and Lim, RK},
title = {Individually Tailored Physiotherapy in Persons With Respiratory Symptoms Related to Post-Acute Sequelae of COVID-19: A Feasibility Study With Mixed Methods.},
journal = {Health science reports},
volume = {8},
number = {10},
pages = {e71367},
pmid = {41132192},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: Post-acute sequelae of COVID-19 (PASC) commonly present with persistent respiratory symptoms, even in individuals with normal chest imaging and pulmonary function. Given the heterogeneity within this population, a personalized approach to respiratory physiotherapy could improve outcomes. The purpose of this study was to assess the feasibility and impact of a tailored respiratory physiotherapy program on health-related quality of life (QoL), functional impairment, and patient-reported outcome measures (PROMs) in individuals with persistent respiratory symptoms due to PASC.<br><br>METHODS: A single-arm, open-label trial was conducted with 13 adults diagnosed with PASC, recruited from Long COVID clinics in Calgary, Canada. Participants underwent an 8-session personalized physiotherapy program, including education, breathing exercises, and strengthening. Feasibility was measured through recruitment, retention, and session completion rates. PROMs were collected at baseline and post-intervention, and qualitative interviews explored participant perspectives.<br><br>RESULTS: The program was highly feasible, with 100% retention and a 99% completion rate. Significant improvements were observed in QoL, functional status (Post COVID-19 Function Status scale), and self-efficacy scores. The 6-min walk test showed clinically meaningful improvements in three out of seven participants. Qualitative interviews (n&#x2009;=&#x2009;8) identified three main themes: struggles with PASC, positive aspects of the program, and benefits from completing it. Participants valued the personalized approach, heart rate monitors, flexible scheduling, and a hybrid of in-person and virtual sessions, reporting increased confidence, improved symptom management, and better mental health.<br><br>CONCLUSION: A personalized respiratory physiotherapy program is feasible and may benefit individuals with PASC. Larger trials are needed to assess long-term efficacy and scalability.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05040893.},
}
@article {pmid41131605,
year = {2025},
author = {Shan, D and Holland, C and Crawford, TJ},
title = {Treatment experiences, preferences, and expectations for cognitive impairments in long COVID among Chinese young and older adults: a constructivist grounded theory study.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {579},
pmid = {41131605},
issn = {1741-7015},
mesh = {Humans ; Male ; Female ; Adult ; *COVID-19/complications/psychology/therapy ; Middle Aged ; China/epidemiology ; *Cognitive Dysfunction/therapy/psychology/etiology ; Aged ; Young Adult ; Grounded Theory ; Adolescent ; *Patient Preference ; Qualitative Research ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Cognitive impairments associated with long COVID disrupt daily functioning and psychological well-being. While increasing research has examined prevalence and mechanisms, little is known about patients' treatment experiences, preferences, and expectations. In the absence of validated effective treatments, integrating these perspectives is essential for guiding research priorities and clinical trial design. In China, where long COVID is an emerging public health concern, awareness of cognitive impairments remains limited and access to specialised care is inadequate. Considering potentially substantial differences in baseline health and treatment expectations between young and older adults, this study aimed to explore and compare their perspectives using a qualitative approach.<br><br>METHODS: We adopted constructivist grounded theory to capture participants' lived experiences and develop a theory grounded in their narratives. Semi-structured online interviews were conducted with 23 individuals recruited via Chinese social media long COVID mutual aid groups, including 10 young adults (18-39&#xa0;years) and 13 older adults (&#x2265;&#x2009;60&#xa0;years). Theoretical sampling guided recruitment and iterative analysis through initial, focused, and theoretical coding, leading to the development of a framework explaining treatment preferences and expectations.<br><br>RESULTS: All participants reported cognitive impairments based on self-perception, with no formal medical diagnoses. We constructed a theoretical framework of "Individualised and Dynamic Adaptation to Cognitive Challenges". Preferences and expectations could be shaped by age, symptom severity, prior management experiences, lifestyle, doctor-patient interactions, and health literacy. Young adults showed a strong preference for non-pharmacological strategies, including self-directed approaches and emotional support to address stigma. Older adults emphasised a balanced use of pharmacological and non-pharmacological interventions, supported by family and structured routines, while expressing holistic expectations that encompassed cognitive, physical, and emotional well-being. Across both groups, improved sleep and psychological health were consistently emphasised.<br><br>CONCLUSIONS: Age-specific differences highlighted the heterogeneity of long COVID experiences and underscored the need for dynamic, patient-centred approaches. Tailored interventions that integrate patient perspectives may enhance care quality and outcomes. Holistic care, particularly for older adults who may face additional comorbidities and functional challenges, is essential. In China, increasing awareness among the public and healthcare providers, reducing stigma, and addressing inequalities in care access should be prioritised.},
}
@article {pmid41130564,
year = {2026},
author = {Masoodi, WTA and Radhi, SW and Al-Hakeim, HK and Abdalsada, HK},
title = {Trace element imbalance as a possible factor in long-COVID pathophysiology: Links to disease duration and inflammation.},
journal = {The American journal of the medical sciences},
volume = {371},
number = {3},
pages = {259-266},
doi = {10.1016/j.amjms.2025.10.013},
pmid = {41130564},
issn = {1538-2990},
mesh = {Humans ; *COVID-19/blood/physiopathology ; *Trace Elements/blood ; Male ; Middle Aged ; Female ; *Inflammation/blood ; Cobalt/blood ; Copper/blood ; SARS-CoV-2 ; Zinc/blood ; Adult ; Aged ; Manganese/blood ; Case-Control Studies ; },
abstract = {BACKGROUND: Long-COVID is defined by persistent symptoms following an initial COVID-19 infection. The normal immune function depends on a precise balance of trace elements, which can provide fresh insights into prospective therapeutic strategies while maintaining oxidative balance and limiting excessive inflammation. Zinc, copper, cobalt, and manganese deficits or excesses can alter the immune system's normal functions and oxidative stress. The study aims to study the trace element profile for predicting long-COVID.<br><br>METHODS: The levels of serum copper and zinc were measured spectrophotometrically. In contrast, cobalt and manganese were measured using flameless atomic absorption spectrophotometry in 60 long-COVID patients and compared with the 30 controls who had previous SARS-CoV-2 infection but were free from long-COVID symptoms.<br><br>RESULTS: Serum levels of copper, cobalt, manganese, and the copper/zinc ratio were considerably elevated in long-COVID patients compared to the control groups. Nonetheless, there was no significant change in zinc levels relative to the control group. The cobalt concentration increases with the duration of the disease and inflammation. Serum manganese level is significantly and negatively correlated with weight. The duration of disease is inversely linked to serum zinc concentrations. There is a substantial correlation between serum copper levels and the period of recovery from acute SARS-CoV-2 infection.<br><br>CONCLUSIONS: Long-COVID is associated with alterations in serum trace elements (copper, cobalt, and manganese). The imbalances in the trace elements are associated with inflammation, duration of disease, and age. These imbalances may contribute to prolonged symptoms and greater disease severity, suggesting that trace element monitoring could be beneficial in managing long-COVID.},
}
@article {pmid41129241,
year = {2026},
author = {Adesse, D and Torices, S and Alcaide, ML and Beurel, E and Pallikkuth, S and Raccamarich, P and Cruz, A and Fonseca Nogueira, N and Jones, DL and Toborek, M},
title = {Plasma Biomarkers of Neurogenesis Are Increased Among People With HIV After COVID.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {101},
number = {2},
pages = {222-231},
doi = {10.1097/QAI.0000000000003785},
pmid = {41129241},
issn = {1944-7884},
support = {MH128022, MH122235, MH072567/MH/NIMH NIH HHS/United States ; P30A1073961//National Institute of Allergy and Infectious Diseases/ ; 444644/2024-5//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; DA050528, and DA039576/DA/NIDA NIH HHS/United States ; P30MH116867/MH/NIMH NIH HHS/United States ; E-26/211.570/2019//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; E-26/211.118/2021//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; E-26/204.304/2024//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; HL126559, HL126559-06S1/HL/NHLBI NIH HHS/United States ; E-26/010-001199/2015//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 8401984391807//Funda&#xe7;&#xe3;o Oswaldo Cruz/ ; E-26/210.247/2020//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; SEI-26 260003/001351/2020//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; P30 AI073961/AI/NIAID NIH HHS/United States ; E-26/201.336/2021//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; },
mesh = {Humans ; *COVID-19/complications/blood ; *HIV Infections/complications/blood ; *Biomarkers/blood ; Male ; Female ; Middle Aged ; Adult ; *Neurogenesis ; Blood-Brain Barrier ; SARS-CoV-2 ; },
abstract = {OBJECTIVES: Although acute COVID does not seem to markedly differ by HIV status, the long-term impact of COVID in people with HIV (PWH) remains unclear.<br><br>METHODS: Samples from 44 participants with or without HIV were obtained approximately 10 days after the initial COVID diagnosis (t = 0) and then 3 (t = 1) and 6 (t = 2) months later. Biomarkers of blood-brain barrier (BBB) and vascular dysfunction, neurogenesis, and inflammatory responses were assessed by multiplex profiling and enzyme-linked immunosorbent assay.<br><br>RESULTS: The majority of inflammatory biomarkers either decreased or remained unchanged during the evaluated time frame. Notable exceptions were IL-9, TNF-&#x3b1;, and CCL-4, which increased at t = 2 compared with earlier time points. The BBB disruption and vascular dysfunction biomarkers (S100&#x3b2; and soluble Intercellular Adhesion Molecule-1, respectively) increased at t = 1 and then returned to basal levels, suggesting transient loss of BBB integrity. No significant changes were observed between people without HIV and PWH across studied inflammatory and BBB markers. Among biomarkers of neurogenesis, eotaxin/CCL11 was not altered, fibroblast growth factor 2 (FGF-2) was transiently decreased at t = 1 in PWH, and granulocyte colony-stimulating factor was elevated at t = 2 in PWH when compared with the previous time points.<br><br>CONCLUSIONS: BBB and vascular dysfunction occur after COVID and may be implicated in the development of post-COVID conditions. HIV-1 infection may potentiate post-COVID-induced neuropathology by impairing neurogenesis.},
}
@article {pmid41127613,
year = {2025},
author = {Escobar Villegas, PA and Cordoba-Melo, BD and Arango-Ibanez, JP and Naranjo-Ramirez, MC and Barbosa, MM and Casanova Rojas, AF and Mina Sánchez, AF and Herrera, CJ and Quintana Da Silva, M&#xc1; and Buitrago Sandoval, AF and Coronel Gilio, ML and Chon Long, FP and Cárdenas Aldaz, L and Gomez-Mesa, JE},
title = {Xerostomia in survivors of severe COVID-19: findings from a Latin American cohort.},
journal = {Frontiers in oral health},
volume = {6},
number = {},
pages = {1633542},
pmid = {41127613},
issn = {2673-4842},
abstract = {OBJECTIVES: SARS-CoV-2 primary affects the respiratory tract; however, evidence suggests the oral cavity can be involved in severe COVID-19 survivors. This study investigates factors associated with xerostomia in severe COVID-19 survivors from a Latin American cohort.<br><br>MATERIALS AND METHODS: A prospective multicenter study from the Latin American Registry of Cardiovascular Disease and COVID-19, analyzed data on 272 severe COVID-19 patients from 7 institutions in 5 countries (Colombia, Dominican Republic, Ecuador, Argentina, and Paraguay). Long-term follow-up assessed demographics characteristics, comorbidities, lifestyle, cardiovascular complications, and oral health. Logistic regression in R software identified factors associated with xerostomia.<br><br>RESULTS: Xerostomia was reported in 20.6% of patients. Among affected individuals, 53.6% were female, while women represented 35.6% of those without the condition. In the overall cohort, the most common comorbidities were overweight/obesity (57.0%), hypertension (55.9%), and dyslipidemia (32.0%). Patients with xerostomia had higher rates of dyslipidemia (48.2% vs. 27.8%) and asthma/COPD (16.1% vs. 4.2%) compared to the group without xerostomia. In multivariable logistic regression, asthma/COPD (aOR: 5.14; 95% CI: 1.76-15.7), palpitations (aOR: 2.47; 95% CI: 1.04-5.94), and chest pain (aOR: 3.74; 95% CI: 1.67-8.43) were independently associated with xerostomia. Conversely, male sex was associated with lower odds of reporting xerostomia (aOR: 0.47; 95% CI: 0.24-0.89).<br><br>CONCLUSION: These findings underscore the need for clinicians to actively assess oral health symptoms such as xerostomia in post-COVID care, particularly in patients with cardiopulmonary comorbidities and persistent systemic symptoms.},
}
@article {pmid41127554,
year = {2025},
author = {Engelberts, R and Douglass, CH and Orozco, A and Eddy, S and Wilkinson, AL and Altermatt, A and van den Toren, S and Lim, MSC},
title = {Understanding Long COVID Among Young People in Victoria, Australia: Prevalence, Impact, and Associated Factors.},
journal = {Public health challenges},
volume = {4},
number = {4},
pages = {e70144},
pmid = {41127554},
issn = {2769-2450},
abstract = {INTRODUCTION: Long COVID is a significant public health concern. This study aimed to identify the prevalence, impact, and factors associated with long COVID among young people in Victoria, Australia.<br><br>METHODS: From April to June 2023, we conducted a cross-sectional online survey of people aged 15-29 years. Participants reported if they had ever experienced long COVID (defined as COVID-19 symptoms for more than 4 weeks) and the impact on their daily functioning. We used multivariable logistic regression to compare participants who reported long COVID with participants who reported acute COVID-19.<br><br>RESULTS: Among 765 participants, 11.2% reported they had ever had long COVID; however, only 1 in 10 had been diagnosed by a medical practitioner. Compared to those without prolonged symptoms, participants reporting long COVID were younger (adjusted odds ratio [aOR]: 0.92; 95% confidence interval [CI]: 0.85-0.99), reported worsened general health (aOR: 8.22; 95% CI: 4.34-15.56), expressed greater concern about getting long COVID again (aOR: 1.20; 95% CI: 1.09-1.33), and had more family or friends who also experienced long COVID (aOR: 4.43; 95% CI: 1.92-10.19). In the past 4 weeks, 79.1% of participants with current long COVID reported difficulties with performing work, and 79.1% accomplished less than desired.<br><br>CONCLUSIONS: One in 10 participants aged 15-29 years experienced long COVID, and most reported negative impacts on their daily life. General practitioners should be aware of the high burden of suspected long COVID in young people and consider supports to mitigate its effects on the health and well-being of this population.},
}
@article {pmid41127487,
year = {2025},
author = {Poulakou, G and Michailidis, V and Gogali, A and Boutlas, S and Kavousanaki, M and Giouleka, P and Stefanidis, A and Styliara, P and Steiropoulos, P and Tzouvelekis, A},
title = {Real-world evidence on long COVID-19 in Greece: A multicenter, cross-sectional study (LONCOV2).},
journal = {IJID regions},
volume = {17},
number = {},
pages = {100761},
pmid = {41127487},
issn = {2772-7076},
abstract = {OBJECTIVES: This study aimed to provide real-world data on the clinical presentation and management of long COVID in Greece.<br><br>METHODS: This non-interventional, nationwide, multicenter, cross-sectional study included adults with a history of symptomatic SARS-CoV-2 infection who presented with suspected long-term COVID-19 manifestations &#x2265;4 weeks after acute infection.<br><br>RESULTS: Among 1011 patients (mean &#xb1; SD age: 55.95 &#xb1; 15.74 years; 56.18% female; 5.04% hospitalized) enrolled between December 2022 and May 2023, the most affected Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) was General disorders and administration site conditions (75.67%), with fatigue/malaise as the predominant symptom (69.93%). This was followed by Respiratory, thoracic, and mediastinal disorders (60.34%), with cough (50.64%) and dyspnea (24.83%) as leading symptoms. Social circumstances, specifically impairments in daily living activities (44.21%), Nervous system disorders (40.26%), mainly headache (23.24%), and Musculoskeletal and connective tissue disorders (27.70%), mainly myalgia (24.63%), were also prominent. The majority (74.38%) had been vaccinated prior to infection, with vaccination shown to be protective against nervous and musculoskeletal symptoms. Females were more prone to systemic, psychiatric, nervous, and musculoskeletal symptoms and impairments in daily activities, but less prone to respiratory symptoms.<br><br>CONCLUSIONS: Multisystem long-term COVID-19 complications were observed, underscoring the importance of multidisciplinary management of this complex, multifaceted condition.},
}
@article {pmid41126309,
year = {2025},
author = {Chatterjee, S and Mahata, J and Kateriya, S and Anirudhan, G},
title = {Pathways in the brain, heart and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence.},
journal = {Cardio-oncology (London, England)},
volume = {11},
number = {1},
pages = {94},
pmid = {41126309},
issn = {2057-3804},
abstract = {BACKGROUND: SARS-CoV-2 non-structural protein 6 (NSP6) in the host's tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Its reported role in immune evasion, viral replication and egress from the cells as well as its gain of function mutations occurring independently in various variants underscores its importance.<br><br>METHODS: Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of regulated host proteins interacting with reported SARS-CoV-2 NSP6 interacting proteins - SIGMAR1, ATP13A3, ATP5MG, and ATP6AP1. Tissue-specific protein interactomes and hub genes in these interactomes were found, and drugs targeting them were sought out.<br><br>RESULTS: Key hub genes in the brain were CCND1, CDK2, CCNA1, CDC6, CDKN1B, SKP1, CCNB1, etc., whereas in the heart were RAB7A, ATP6V0D1, LAMP2, TGFB1, CANX, LGALS3, etc. Lung hub genes were ATP6V0A1, ATP6V0A2, ATP6V0D1, ATP6V1D, ATP6V1B1, ATP6V1E1, TGFB1, EGF, TGFBR2, and LGALS3. Hub gene associated pathways in the brain were iron uptake and transport, G1/S transition, and small cell Lung cancer. Differentiation of dendritic cells and reduction of intraphagosomal pH to 5 - were prominent pathways in lung. In heart, phagosome associated pathways, and regulation of intracellular were prominent. Key therapeutic targets identified in the brain are CDK2, targeted by acetaminophen and raltitrexed; CCNE1 by palbociclib; and CCND1 by palbociclib, acetaminophen, lapatinib, doxorubicin, and methotrexate. In the heart, TGFB1 and APP are targeted by inositol, while LGALS3, upregulated after COVID-19 can be targeted by non-approved drugs (Belapectin, Olitigaltin, Lactose anhydrous, Davanat). In the lungs, TGFB1 and TGFBR2 are targeted by irinotecan, and EGF by cetuximab.<br><br>CONCLUSIONS: This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19.},
}
@article {pmid41125642,
year = {2025},
author = {Guzmán Rivera, J and Zheng, H and Richlin, B and Suarez, C and Gaur, S and Ricciardi, E and Hasan, UN and Cuddy, W and Singh, AR and Bukulmez, H and Kaelber, DC and Kimura, Y and Brady, PW and Wahezi, D and Rothschild, E and Lakhani, SA and Herbst, KW and Hogan, AH and Salazar, JC and Moroso-Fela, S and Roy, J and Kleinman, LC and Horton, DB and Moore, DF and Gennaro, ML},
title = {Mass spectrometry combined with machine learning identifies novel protein signatures as demonstrated with multisystem inflammatory syndrome in children.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {36843},
pmid = {41125642},
issn = {2045-2322},
support = {R33 HD105613/HD/NICHD NIH HHS/United States ; R61HD105619//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; UM1 TR004789/TR/NCATS NIH HHS/United States ; R61 HD105613/HD/NICHD NIH HHS/United States ; R61 HD105593/HD/NICHD NIH HHS/United States ; R33 HD105619/HD/NICHD NIH HHS/United States ; R61 HD105619/HD/NICHD NIH HHS/United States ; R33 HD105593/HD/NICHD NIH HHS/United States ; R01 AI158911/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/diagnosis/blood/complications ; *Systemic Inflammatory Response Syndrome/diagnosis/blood/metabolism ; Child ; Male ; *Mass Spectrometry/methods ; Female ; Proteomics/methods ; *Machine Learning ; SARS-CoV-2 ; Child, Preschool ; Support Vector Machine ; Mucocutaneous Lymph Node Syndrome/blood/diagnosis ; Biomarkers/blood ; Infant ; *Blood Proteins/analysis ; ROC Curve ; Sensitivity and Specificity ; },
abstract = {Rapid and accurate diagnosis of emerging inflammatory illnesses is challenging due to overlapping clinical features with existing conditions. We demonstrate an approach that integrates proteomic analysis with machine learning to identify diagnostic protein signatures, using the example of SARS-CoV-2-induced multisystem inflammatory syndrome in children (MIS-C). We used plasma samples collected from subjects diagnosed with MIS-C and compared them first to controls with asymptomatic/mild SARS-CoV-2 infection and then to controls with pneumonia or Kawasaki disease. We used mass spectrometry to identify proteins and support vector machine (SVM) algorithm-based classification schemes to identify protein signatures. Diagnostic accuracy was assessed by calculating sensitivity, specificity, and area under the ROC curve (AUC), and corrected for overfitting by cross-validation. Proteomic analysis of a training dataset containing MIS-C (N = 17), and asymptomatic/mild SARS-CoV-2 infected control samples (N = 20) identified 643 proteins, of which 101 were differentially expressed. Plasma proteins associated with inflammation increased, and those associated with metabolism and coagulation decreased in MIS-C relative to controls. The SVM machine learning algorithm identified a three-protein model (ORM1, AZGP1, SERPINA3) that achieved 90.0% specificity, 88.2% sensitivity, and 93.5% AUC, distinguishing MIS-C from controls in the training set. Performance was retained in the validation dataset utilizing MIS-C (N = 19) and asymptomatic/mild SARS-CoV-2 infected control samples (N = 10) (90.0% specificity, 84.2% sensitivity, 87.4% AUC). We next replicated our approach to compare MIS-C with similarly presenting syndromes, such as pneumonia (N = 17) and Kawasaki disease (N = 13), and found a distinct three-protein signature (VWF, FCGBP, and SERPINA3) that accurately distinguished MIS-C from the other conditions (97.5% specificity, 89.5% sensitivity, 95.6% AUC). A software tool was also developed that may be used to evaluate other protein signatures using our data. These results demonstrate that the use of mass spectrometry to identify candidate plasma proteins followed by machine learning, specifically SVM, is an efficient strategy for identifying and evaluating biomarker signatures for disease classification.},
}
@article {pmid41125258,
year = {2025},
author = {Ortega-Martin, E and Richards-Belle, A and Newlands, F and Shafran, R and Stephenson, T and Rojas, N and Batura, N and Buszewicz, M and Dalrymple, E and Heyman, I and , and Pinto Pereira, SM},
title = {Children and young people with persistent post-COVID-19 condition over 24 months: a mixed-methods study.},
journal = {BMJ paediatrics open},
volume = {9},
number = {1},
pages = {},
pmid = {41125258},
issn = {2399-9772},
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; Female ; Adolescent ; Male ; Child ; England/epidemiology ; SARS-CoV-2 ; Quality of Life ; },
abstract = {PURPOSE: While most children and young people (CYP) recover from COVID-19, some develop 'post-COVID-19 condition' (PCC), affecting their health and well-being. We explored (1) whether distinct persistent PCC symptom subgroups exist in CYP and whether these subgroups remain stable up to 24 months postinfection; (2) whether impairments differ across subgroups and (3) how CYP with persistent PCC describe the evolving impact of the pandemic/lockdowns on their health and experiences up to 24 months postinfection.<br><br>METHODS: A cohort of CYP across England was recruited in 2020-2021 (the children and young people with Long COVID study). A subsample of 68 CYP meeting the PCC Delphi research definition at 3, 6, 12 and 24&#x2009;months post-PCR-confirmed infection was analysed. Latent class analysis identified symptom subgroups (objective 1); associations with impairments (measured via EuroQol Five Dimensions Youth) were examined (objective 2). Free-text responses from six CYP at all four follow-up points (n=24) were thematically analysed to capture evolving experiences (objective 3).<br><br>RESULTS: Included CYP were older (72.1% were 15-17 years), female (82.4%) and white (80.9%). Two symptom groups emerged: a frequent symptom subgroup (median: 6.5-9 symptoms over time, mainly shortness of breath and tiredness); and a less frequent symptom subgroup (median: 4-5 symptoms, mostly tiredness). Generally, no association was found between symptom subgroups and impairments. Qualitative analysis indicated feelings of anxiety, respiratory problems and concerns around relaxation of lockdown restrictions persisted over follow-up. School-related worries were transient.<br><br>DISCUSSION: Even CYP with persistent PCC characterised by fewer symptoms experience long-term anxiety and impact, emphasising even few symptoms can be debilitating and underscoring the need for personalised PCC management for CYP.},
}
@article {pmid41124977,
year = {2025},
author = {Sarkanen, T and Merikanto, I and Bjorvatn, B and Chung, F and Holzinger, B and Morin, CM and Penzel, T and De Gennaro, L and Wing, YK and Benedict, C and Xue, P and Reis, C and Korman, M and Landtblom, AM and Matsui, K and Hrubos-Strøm, H and Mota-Rolim, S and Nadorff, MR and Berezin, L and Liu, Y and Scarpelli, S and Brandao, LE and Cedernaes, J and Partinen, E and Bolstad, CJ and Plazzi, G and Espie, CA and Partinen, M and Dauvilliers, Y},
title = {Long COVID as a risk factor for hypersomnolence and fatigue: insights from the 2nd International Covid Sleep Study Collaboration (ICOSS-2).},
journal = {Sleep medicine},
volume = {136},
number = {},
pages = {106764},
doi = {10.1016/j.sleep.2025.106764},
pmid = {41124977},
issn = {1878-5506},
mesh = {Humans ; *Fatigue/epidemiology/etiology ; *COVID-19/complications/epidemiology ; Female ; Male ; Adult ; *Disorders of Excessive Somnolence/epidemiology/etiology ; Risk Factors ; Middle Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; Quality of Life ; Severity of Illness Index ; },
abstract = {BACKGROUND: Hypersomnolence, defined as excessive daytime sleepiness (EDS), excessive quantity of sleep (EQS), sleep inertia, and fatigue reduce quality of life. We assessed associations of the COVID-19 pandemic, infection without long-term sequalae (short COVID, SC), and long COVID (LC) on hypersomnolence and fatigue in a large population across different countries.<br><br>METHODS: As part of an online questionnaire (ICOSS-2), we assessed EDS via the Epworth Sleepiness Scale (ESS), fatigue via Fatigue Severity Scale (FSS), and sleep duration at night and per 24&#xa0;h. We also assessed the associations with EDS, sleep inertia, fatigue and napping by their frequencies, during the pandemic in COVID-negative, SC and LC participants.<br><br>RESULTS: The final cohort comprised 13,656 participants (69.1&#xa0;% women, 42.7&#xa0;&#xb1;&#xa0;16.6 years), with 12.4&#xa0;% classified SC and 7.5&#xa0;% LC. ESS scores were higher in LC (9.16, 95&#xa0;% CI [8.78, 9.53]) compared to SC (7.26, [6.97, 7.55]) and COVID-negative (6.53, [6.43, 6.63]). LC also had higher odds of ESS>10 (OR 1.58, [1.18,2.09]). FSS scores were higher in LC (median 51, IQR 39-59) than SC (34, 25-44) and COVID-negative (35, 25-45), with LC having 2.22 higher odds of severe fatigue. LC cases also reported more EQS (&#x2265;10/24&#xa0;h) than COVID-negative. Worsening of EDS, fatigue, sleep inertia, and napping was reported during pandemic to a greater extent in LC.<br><br>CONCLUSIONS: LC was associated with higher levels of hypersomnolence and fatigue than in SC or COVID-negative participants, highlighting the need for interventions and future research focusing on sleep symptoms and their relation to long-term health outcomes.},
}
@article {pmid41122751,
year = {2025},
author = {Toepffer, A and Früh, M and Rocktäschel, T and Ballez, J and Troll, M and Güllmar, D and Finke, K and Reuken, PA and Stallmach, A and Vonderlind, S and Dunay, IR and Gaser, C and Walter, M and Besteher, B},
title = {Cognition-associated gray matter volume alterations in long-COVID show sex-specific patterns.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1653295},
pmid = {41122751},
issn = {1664-0640},
abstract = {INTRODUCTION: The long-term effects of the coronavirus disease 2019 (COVID-19) are a major concern in today's society, with cognitive impairment being an important manifestation. Notably, men and women exhibit differences in disease progression and the prevalence of long-COVID. This study aims to investigate sex differences in cognitively impaired long-COVID individuals and their potential association with alterations in gray matter volume (GMV).<br><br>METHODS: We conducted MRI at 3 Tesla to investigate brain structural correlates of cognitive impairment in long-COVID patients using voxel-based morphometry (VBM) and compared these patients to a healthy control (HC) group (n=30, female=13, male=17). Long-COVID patients underwent scanning and neuropsychiatric assessment on average 9.9 months after their acute and mostly mild COVID-19 infection. Based on Montreal Cognitive Assessment (MoCA) scores, they were classified into two groups: the PCn group, showing preserved cognitive function with MoCA scores of 26 or higher (n=36, female=23, male=13), and the PCcog group, characterized by cognitive impairment with MoCA scores below 26 (n=28, female=15, male=13). Subsequent analyses were performed separately for males and females to investigate sex-specific brain structural correlates of cognitive impairment.<br><br>RESULTS: Our analysis revealed significant GMV alterations in long-COVID patients across various brain regions, encompassing both shared and sex-specific regional changes. In females, these alterations were more restricted, affecting anterior frontal, limbic, and diencephalic regions. In males, GMV alterations were more widespread, involving neocortical regions such as the parietal, occipital, and motor cortices, and were characterized by a greater number of affected clusters.<br><br>DISCUSSION: Our findings demonstrate GMV alterations in both men and women with cognitive impairment, exhibiting sex-specific differences in affected regions. These differences suggest potentially distinct underlying mechanisms, highlighting the need for further research into their functional implications and relevance for personalized treatment strategies.},
}
@article {pmid41120952,
year = {2025},
author = {He, X and Gao, W},
title = {Persistent pain and brain fog after COVID-19 infection in European adults aged 50 and over: a population-based longitudinal study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1366},
pmid = {41120952},
issn = {1471-2334},
mesh = {Humans ; *COVID-19/complications/epidemiology/psychology ; Male ; Longitudinal Studies ; Female ; Aged ; Middle Aged ; Europe/epidemiology ; Prospective Studies ; *Depression/epidemiology ; SARS-CoV-2 ; *Pain/epidemiology/etiology ; Aged, 80 and over ; Risk Factors ; },
abstract = {BACKGROUND: Psychological distress has been identified as a risk factor for long COVID in individuals infected with COVID-19. Little is known about the differences in long COVID symptom profiles between older adults with pre-existing depression and those without.<br><br>METHODS: A population-based longitudinal prospective study was performed using the Survey of Health, Ageing and Retirement in Europe (SHARE) with participants aged 50 years and older. Depression was assessed by the EURO-D scale at the baseline. Long COVID symptoms were self-reported by participants during the 12-month follow-up. A hurdle negative binomial model was employed to assess the impact of pre-existing depression on the burden of long COVID. We compared the differences in symptoms between participants with pre-existing depression and those without with the Chi-squared test.<br><br>RESULTS: Participants with pre-existing depression had an approximately 16% increased risk of experiencing additional persistent symptoms after COVID-19 infection. During the 12-month follow-up following COVID-19 infection, the prevalence of headaches (32.2% vs. 25.9%; P&#x2009;=&#x2009;0.027), body aches or joint pain (38.5% vs. 29.4%; P&#x2009;<&#x2009;0.001), and confusion (10.6% vs. 7.6%; P&#x2009;<&#x2009;0.01) were significantly higher among participants with pre-existing depression than among those without.<br><br>CONCLUSION: Older adults with pre-existing depression had a higher burden of long COVID following COVID-19 infection and they were more likely to suffer from persistent physical pain and confusion compared to those without a history of depression.},
}
@article {pmid41117750,
year = {2025},
author = {Dowrick, A and MacLean, A and Ziebland, S and Greenhalgh, T},
title = {Trust in Transition: Exploring Changing Trust in Vaccination in the Context of Long Covid in the United Kingdom.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70459},
pmid = {41117750},
issn = {1369-7625},
support = {//This work is based on independent research funded by the National Institute for Health and Care Research (NIHR) (COV-LT2-0005), the Scottish Government Chief Scientist Office (reference COV/LTE/20/04), and Balvi Philanthropic Fund./ ; },
mesh = {Humans ; *Trust/psychology ; *COVID-19 Vaccines/administration &amp; dosage/therapeutic use ; United Kingdom ; *COVID-19/prevention &amp; control/psychology ; Female ; Male ; Middle Aged ; Adult ; Interviews as Topic ; *Vaccination/psychology ; Aged ; Qualitative Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: New drugs and vaccines usually come with the promise and hope of benefit. We explore stories about the variable and sometimes disappointing effects of Covid-19 vaccines in the context of post-Covid-19 syndrome ('long Covid'), aiming to understand how people with long Covid made sense of unexpected vaccine responses and how these experiences impacted their trust in vaccination.<br><br>METHODS: We carried out 33 interviews with people who described both positive and negative unexpected vaccine experiences connected to long Covid.<br><br>RESULTS: Trust and distrust in the multiple potential roles of Covid vaccines in relation to long Covid impacted perspectives on future vaccine uptake. Some participants feared being labelled as anti-vaxx if they discussed unexpected vaccine impacts. Disengagement by healthcare professionals in discussions about the possibility of individual vaccine harms had the inverse consequence of limiting uptake of further Covid vaccines. Distrust could also grow in relation to unrealised benefits of vaccination-in this case, the official role as protection from severe infection and the unofficial role of treatment. Participants who trusted vaccines as a form of treatment struggled to access them for this use.<br><br>CONCLUSION: The gap between scientific discourse-which recognised potential benefits and potential harms of vaccines in relation to long Covid-and public health discourse, which tended to focus on protection from infection, contributed to difficulties in maintaining trust after unexpected vaccine experiences. Further research to better characterise who is likely to benefit from vaccination and who might be at risk of worsening long Covid symptoms would enable better conversations between patients and healthcare professionals when making decisions about further vaccination.<br><br>The study was guided by a patient and public involvement and engagement (PPIE) group from project development through to dissemination. People with long Covid supported recruitment strategies, informed the development of topic guides, reviewed findings and offered suggestions for dissemination. Study participants were also invited to review and feedback on findings.},
}
@article {pmid41117273,
year = {2026},
author = {Oba, S and Hosoya, T and Iwai, H and Yasuda, S},
title = {Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.},
journal = {Immunological medicine},
volume = {49},
number = {1},
pages = {35-58},
doi = {10.1080/25785826.2025.2570902},
pmid = {41117273},
issn = {2578-5826},
mesh = {Humans ; *COVID-19/therapy/epidemiology/complications/immunology/physiopathology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use ; },
abstract = {Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.},
}
@article {pmid41115626,
year = {2025},
author = {Oh, J and Kim, S and Jo, H and Park, J and Son, Y and Lee, S and Lee, J and Smith, L and Kang, J and Jung, J and Lee, H and Yon, DK},
title = {Burden of post-acute sequelae of COVID-19 in patients with type 2 diabetes: a binational cohort study in South Korea and Japan.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {161},
number = {},
pages = {108143},
doi = {10.1016/j.ijid.2025.108143},
pmid = {41115626},
issn = {1878-3511},
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/epidemiology ; *COVID-19/complications/epidemiology ; Female ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Japan/epidemiology ; Aged ; SARS-CoV-2 ; Cohort Studies ; Adult ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Proportional Hazards Models ; },
abstract = {BACKGROUND: The long-term sequelae of COVID-19 remain a growing concern; however, a limited study targeting individuals with preexisting type 2 diabetes mellitus (T2DM) and Asian populations has been conducted. This large-scale, binational cohort study with extended follow-up aimed to evaluate the risk of post-acute sequelae of COVID-19 across multiple organ systems in individuals with T2DM.<br><br>METHODS: This study used binational, population-based cohorts in South Korea (K-COV-N; discovery cohort; n = 3,002,271) and Japan (JMDC; validation cohort; n = 1,125,045). All individuals aged >19 years were included from January 1, 2020, to December 31, 2022. We estimated the long-term risk of post-acute sequelae following SARS-CoV-2 infection. We defined the primary outcome as the onset of 65 diseases across 9 organ systems beyond the first 30 days after SARS-CoV-2 infection. After applying propensity score-based overlap weighting, we utilized Cox proportional hazards models to estimate adjusted hazard ratios (HRs) with 95% CIs for post-acute sequelae of COVID-19 within the weighted population. We further examined how the risk of sequelae changed over time following COVID-19 diagnosis. We also conducted multiple subgroup analyses on the severity of COVID-19, COVID-19 vaccination status, and T2DM-related complications.<br><br>RESULTS: In the overlap-weighted discovery cohort, 1,056,277 individuals with preexisting T2DM were analyzed (mean age: 58.06 years [SD, 10.02]; 39.41% females). Compared with non-infected individuals, those with SARS-CoV-2 infection showed an increased long-term risk of sequelae across eight organ systems, including cardiovascular diseases (aHR, 1.11 [95% CI, 1.09-1.13]), dermatologic conditions (aHR, 1.20 [1.10-1.31]), endocrine disorders (aHR, 1.04 [1.01-1.08]), gastrointestinal diseases (aHR, 1.11 [1.07-1.14]), hepato-biliary-pancreatic disorders (aHR, 1.07 [1.03-1.11]), kidney disorders (aHR, 1.09 [1.03-1.16]), neurological disorders (aHR, 1.11 [1.03-1.20]), and pulmonary diseases (aHR, 1.11 [1.04-1.18]). Specifically, of 65 diseases, 45 showed a significantly elevated incident risk following a COVID-19 diagnosis. The risk of sequelae was higher in individuals with moderate-to-severe COVID-19 and persisted up to 12 months post-infection, with attenuation thereafter. COVID-19 vaccination was associated with reduced sequelae risk of developing some sequelae; however, the risk was still generally higher than in non-infected individuals. Similar trends were observed in the validation cohort, where all 65 specific diseases showed significant associations with long-term sequelae.<br><br>CONCLUSION: Among individuals with preexisting T2DM, SARS-CoV-2 infection was associated with an increased risk of long-term sequelae across multiple organ systems, particularly in moderate-to-severe cases. Risks peaked within 12 months and gradually subsided thereafter, highlighting the enduring impact of COVID-19 and the need for sustained monitoring and preventive care in this high-risk population.},
}
@article {pmid41114999,
year = {2025},
author = {Bassi, A and Devasenapathy, N and Thankachen, SS and Ghosh, A and Rastogi, A and Khan, R and Bahuleyan, B and Gummidi, B and Basheer, A and Sreelal, TP and Bangi, A and Shaikh, Y and Sahu, D and Rathore, V and Bhalla, A and Samita, S and Blessan, M and Dipu, TS and Jain, M and Prajapati, AM and Bodhey, NK and Jha, V},
title = {Effectiveness of Colchicine for the Treatment of Long COVID: A Randomized Clinical Trial.},
journal = {JAMA internal medicine},
volume = {185},
number = {12},
pages = {1462-1470},
doi = {10.1001/jamainternmed.2025.5408},
pmid = {41114999},
issn = {2168-6114},
mesh = {Humans ; *Colchicine/therapeutic use/administration &amp; dosage ; Male ; Female ; Middle Aged ; Double-Blind Method ; *COVID-19/complications/physiopathology ; *COVID-19 Drug Treatment ; Adult ; SARS-CoV-2 ; Treatment Outcome ; *Anti-Inflammatory Agents/therapeutic use ; Quality of Life ; },
abstract = {IMPORTANCE: Long COVID is characterized by persistent symptoms after SARS-CoV-2 infection, with inflammation playing a key role in pathogenesis. Colchicine, an established anti-inflammatory agent, may reduce these symptoms by targeting inflammatory pathways.<br><br>OBJECTIVE: To evaluate the superiority of colchicine over placebo in improving functional outcome at 52 weeks from baseline.<br><br>This double-blind, 1:1 randomized clinical trial recruited participants with confirmed SARS-CoV-2 infection and persistent symptoms from 8 hospitals in 6 states in India between January 2022 and July 2023. Individuals were eligible if they had functional limitation (Post-COVID-19 Functional Status scale grade 2 or more) and/or elevated inflammatory markers (high-sensitivity C-reactive protein >0.20 mg/dL and/or neutrophil to lymphocyte ratio >5). Outcomes were assessed at 12, 26, and 52 weeks after randomization. Data were analyzed from January to February 2025.<br><br>INTERVENTIONS: Participants were randomly assigned to receive colchicine, 0.5 mg, once or twice daily, based on body weight, or placebo for 26 weeks.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was the change in distance walked during a 6-minute walk test from baseline to 52 weeks. Secondary outcomes included changes in inflammatory markers and patient-reported outcome measures, such as quality of life, anxiety, depression, fatigue, dyspnea, measured using validated instruments.<br><br>RESULTS: Of 346 participants included in the modified intention-to-treat analysis, 209 (60.4%) were female, 137 (39.6%) were male, and the mean (SD) age was 46 (12) years. At 52 weeks, there was no difference in mean (SD) change in 6-minute walk test distance between the colchicine and placebo groups (colchicine, 35.5 [19.76] m; placebo, 29.96 [19.83] m; mean difference, 5.59 m; 95% CI, -9.00 to 20.18; P&#x2009;=&#x2009;.45). Similar null findings were seen across all predefined outcomes, except for a small, nonclinically relevant difference in the mean (SD) ratio of forced expiratory volume in 1 second to forced vital capacity (colchicine, -0.02 [0.03]; placebo, -0.06 [0.03]; mean difference, 0.04; 95% CI, 0.02 to 0.07; P&#x2009;=&#x2009;.001).<br><br>CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among adults with long COVID, colchicine did not improve functional capacity, respiratory function, or inflammatory markers. These findings underscore the need to explore alternative therapeutic approaches for long COVID.<br><br>TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2021/11/038234.},
}
@article {pmid41114667,
year = {2025},
author = {Raineri, A and Rueegg, S and Zimmermann, P and Regamey, N and Benden, C and Haile, SR and Ulyte, A and Puhan, MA and Kriemler, S and Radtke, T},
title = {Long COVID in children and adolescents: results from three cross-sectional school-based cohorts with adjudication.},
journal = {Swiss medical weekly},
volume = {155},
number = {},
pages = {4337},
doi = {10.57187/s.4337},
pmid = {41114667},
issn = {1424-3997},
mesh = {Adolescent ; Child ; Female ; Humans ; Male ; *COVID-19/epidemiology/diagnosis ; Cross-Sectional Studies ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; Prevalence ; Prospective Studies ; Schools ; Switzerland/epidemiology ; },
abstract = {STUDY AIMS: The prevalence of Long COVID in children and adolescents is heterogeneous, ranging from 1% to 51%, depending on the population studied. The lack of a standardised approach for establishing a Long COVID diagnosis in children and adolescents complicates the accurate assessment of prevalence, risk factors and outcomes. The present study aimed to examine the value of standardised interviews and an adjudication process to better understand self- or proxy-reported symptoms lasting longer than 12 weeks compatible with Long COVID in children and adolescents during the COVID-19 pandemic.<br><br>METHODS: We conducted a school-based, prospective cohort study (Ciao Corona) from March 2020 to July 2022 in the Canton of Zurich, Switzerland. Of 156 invited schools, 55 agreed to participate. Primary schools were randomly selected across all 12 districts of the Canton of Zurich, with nearby secondary schools subsequently invited. Within participating schools, classes were randomly selected, stratified by school level, and all students aged 6-17 years in selected classes were eligible. At three different time points (March/April 2021, November/December 2021 and June/July 2022), school-aged children and adolescents underwent serology testing and completed online questionnaires, including questions on symptoms lasting &#x2265;12 weeks compatible with Long COVID. We invited those with persisting symptoms and who were seropositive for SARS-CoV-2 - whether "infected" i.e. infection and no vaccination or having "hybrid immunity" i.e. infection and vaccination - to participate in interviews to allow us to better understand the pattern, severity and timing of the reported symptoms. An adjudication process with experts then followed to assess the probability of Long COVID.<br><br>RESULTS: 39/1120 (3.5%) seropositive children and adolescents (i.e. infected or with hybrid immunity) reported persisting symptoms (&#x2265;12 weeks). The most frequently reported symptoms were headache, tiredness and stomach ache. In 20/39 (51%) with persisting symptoms who agreed to be interviewed,&#xa0;the adjudication committee concluded that Long COVID was unlikely in 13 (65%), possible in 7 (35%) and likely in 0 participants.<br><br>CONCLUSIONS: Relying exclusively on self- or proxy-reported questionnaire data, without more detailed information may overestimate Long COVID in children and adolescents. Implementing standardised interviews and an adjudication process helps to contextualise self- or proxy-reported symptoms compatible with Long COVID.<br><br>TRIAL REGISTRATION: &#xa0;https://clinicaltrials.gov&#xa0;NCT04448717.},
}
@article {pmid41112288,
year = {2025},
author = {Rossi, N and Benítez-Cruz, J and Marín-García, P and Azcárate, IG and González-Escalada, A and Hervás, OG and Alarcón, B and Regueiro, JR and Bautista, JM and Martinez-Quiles, N},
title = {Post-COVID syndrome patients show reduced anti-Spike antibodies compared to COVID-recovered controls, but enhanced IgG4/IgG1 switch after the third vaccine dose.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1670324},
pmid = {41112288},
issn = {1664-3224},
mesh = {Humans ; *Immunoglobulin G/immunology/blood ; *COVID-19/immunology ; *Spike Glycoprotein, Coronavirus/immunology ; *Antibodies, Viral/blood/immunology ; Male ; *SARS-CoV-2/immunology ; Female ; Middle Aged ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; Adult ; Aged ; Vaccination ; },
abstract = {INTRODUCTION: Long COVID and post-COVID syndromes represent a significant global health crisis and a substantial societal challenge. Although an altered immunological response has been suggested as a possible underlying mechanism, the antibody response to vaccination and infection of the patients remains unclear.<br><br>METHODS: We studied a post-COVID syndrome cohort compared to a COVID-recovered cohort. Initially, we established the risk factors and the evolution of symptoms. Then, we analyzed the antibody response, focusing on immunoglobulin subclasses. Apart from determining immunoglobulin G (IgG) against the Nucleocapsid, which is a marker of infection, we analyzed IgG and its subclasses against the full-length Spike, and against the receptor-binding domain (RBD). Additionally, we examined the switch to IgG4, which can be promoted by repeated antigen exposure.<br><br>RESULTS: We show the major risk factors for developing post-COVID syndrome, such as infection before vaccination and comorbidities. Furthermore, we describe the evolution of the post-COVID symptoms, which agrees with previous reports. Regarding the antibody response, we found that compared to COVID-recovered individuals, post-COVID patients present readily detectable anti-Nucleocapsid IgG but low quantities of anti-Spike antibodies. Nevertheless, the anti-RBD IgG1 levels are similar between post-COVID and COVID samples. Interestingly, post-COVID patients with three vaccine doses, who were infected before vaccination by the Wuhan strain and subsequently reinfected post-Omicron, show decreased Spike response but intensified anti-RBD IgG4/IgG1 switch, compared to their non-reinfected post-COVID counterparts.<br><br>DISCUSSION: Our results support a differential antibody response in post-COVID versus COVID-recovered patients, which might be relevant for post-COVID syndrome treatment, including appropriate recall vaccination strategies for the still-circulating SARS-CoV-2.},
}
@article {pmid41111962,
year = {2025},
author = {Iftekhar, N and Wilson, A and Nguty, L and Al-Hilali, H and Al-Hilali, Y and Jain, K and Braka, A and Osborne, T and Sivan, M},
title = {Normative data for the 10-min lean test in adults without orthostatic intolerance.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1625216},
pmid = {41111962},
issn = {1664-2295},
abstract = {BACKGROUND: Orthostatic intolerance syndromes such as Orthostatic Hypotension (OH) and Postural Orthostatic Tachycardia Syndrome (PoTS) are common symptoms seen in post-infection conditions and other neurological conditions with autonomic dysfunction. The 10-min Lean Test (LT) is an objective clinical test used to assess these symptoms and direct management. There is, however, no robust literature on normative data for this test, particularly from a younger population.<br><br>AIMS: The aim of this study was to produce a healthy control data set for LT, which can be used for comparison with the patient population with health conditions.<br><br>METHODS: Individuals recruited into the study had no history or symptoms of orthostatic intolerance; autonomic dysfunction; post-infection conditions (such as long COVID); or other neurological conditions with hemodynamic instability. Participants were primarily recruited from the general population in a metropolitan city. All participants underwent a standardized LT. Lying Blood Pressure (BP) and Heart Rate (HR) after 2&#x202f;min of lying down supine was recorded, followed by BP and HR recordings at every minute of standing (leaning against a wall) up to 10&#x202f;min, along with recording subject-reported symptoms at each time point.<br><br>RESULTS: A complete dataset was available for 112 individuals (60.7% Female, 39.3% Male). The population was 61.6% Caucasian, 8.0% Asian, 3.6% Black/Caribbean, 9.8% Mixed, and 17.0% Other; the mean age was 35.3&#x202f;&#xb1;&#x202f;15.1, with a BMI of 24.8&#x202f;&#xb1;&#x202f;4.0; 30.6% of individuals had a background medical condition, but none of the exclusion criteria. During LT, upon standing, the average change of HR was an increase of 9.89&#x202f;&#xb1;&#x202f;8.15&#x202f;bpm. The sustained HR increase (HR increase sustained at two consecutive readings) was an average of 6.23&#x202f;&#xb1;&#x202f;6.94&#x202f;bpm. The predominant response with BP was an increase of systolic BP, with the average initial increase being 7.55&#x202f;&#xb1;&#x202f;10.88&#x202f;mmHg. None of the participants met the diagnostic criteria for symptomatic OH or PoTS during LT.<br><br>CONCLUSION: For the first time in the current literature, 10-min LT data from a relatively younger population without orthostatic intolerance have been gathered. This normative data will help interpret LT findings in younger patients with orthostatic Intolerance better and be useful in managing dysautonomia in specific conditions.},
}
@article {pmid41111760,
year = {2025},
author = {Bouchari, A and Dami, F and El Hammouti, M and Ben Driss Alami, S and Hanafi, H and El Maakoul, S and Assem, M},
title = {Long-Term Outcomes of Chronic Hemodialysis Patients Following SARS-CoV-2 Infection.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92535},
pmid = {41111760},
issn = {2168-8184},
abstract = {INTRODUCTION: The COVID-19 pandemic has had a significant impact on patients undergoing chronic hemodialysis (CHD). Several studies have explored the long-term outcomes of CHD patients who recovered from SARS-CoV-2 infection. This study aims to identify the factors associated with persistent symptoms (long COVID) among CHD patients.<br><br>METHODS: We conducted a multicenter, descriptive, and analytical cohort study across nine hemodialysis centers (public, private, and nonprofit) in the city of Tangier. Data were collected through interviews with patients and a review of their medical records. Statistical analysis was performed using IBM SPSS Statistics version 25.<br><br>RESULTS: Among 945 CHD patients, 163 had a documented SARS-CoV-2 infection, with a median age of 55 years (interquartile range (IQR): 43-67). The most frequently reported post-infection symptoms were fatigue (62%), anxiety (53%), arthralgia (40%), cough (33%), weight loss (29%), sleep perturbations (28%), anosmia (30%), dyspnea (25%), anorexia (24%), dysgeusia (18%), and concentration difficulties (16%). After adjusting for diabetes, obesity, oxygen therapy, hospitalization, and use of hydroxychloroquine or corticosteroids, diabetes emerged as the main factor for long COVID (OR = 3.8; 95% CI (1.5-9.6); p = 0.004). Fatigue was significantly associated with diabetes (OR = 2.9; 95% CI (1.3-6.5); p = 0.01) and female gender (OR = 2.1; 95% CI (1.02-4.2); p = 0.04). Anxiety was linked to diabetes (OR = 2.6; 95% CI (1.2-5.5); p = 0.01) and obesity (OR = 2.5; 95% CI (1.01-6.4); p = 0.04). Dyspnea was associated with obesity (OR = 4.0; 95% CI (1.4-10.4); p = 0.004).<br><br>CONCLUSION: Our study highlights the substantial prevalence of persistent post-COVID-19 symptoms among CHD patients. The findings emphasize the necessity of individualized long-term care in this high-risk group.},
}
@article {pmid41109882,
year = {2025},
author = {Bousquet, C and Pereda-Loth, V and Pierron, D and Gonzalez-Navarro, M and Avila-Ríos, S and Mandairon, N and Ferdenzi, C and Bensafi, M},
title = {Self-reported cognitive and affective complaints associated with olfactory loss in an online survey of individuals with COVID-19.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {282},
number = {12},
pages = {6257-6267},
pmid = {41109882},
issn = {1434-4726},
mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Self Report ; *Olfaction Disorders/epidemiology/psychology/etiology ; Middle Aged ; Adult ; SARS-CoV-2 ; France/epidemiology ; Mexico/epidemiology ; Pandemics ; Aged ; *Betacoronavirus ; Surveys and Questionnaires ; Prevalence ; *Pneumonia, Viral/psychology/epidemiology/complications ; *Mood Disorders/epidemiology ; },
abstract = {PURPOSE: The symptomatology associated with COVID-19 is very diverse, ranging from flu-like symptoms to those affecting olfaction, cognition or mood for long periods. The present study explored the associations between self-reported olfactory deficits and cognitive and emotional complaints in a large-scale online survey conducted among individuals who had COVID-19.<br><br>METHODS: Two complementary online studies were set up, one in France and the other in Mexico, involving 3108 and 364 volunteers respectively, to investigate the link between olfactory loss in COVID-19 and self-reported cognitive and emotional changes. Cognitive and affective complaints were assessed using simple yes/no items inspired by previously published studies, but not based on standardized clinical questionnaires.<br><br>RESULTS: A first result was that cognitive difficulties are more frequent in COVID-19 individuals with long-standing olfactory disorders than in patients who have recently developed olfactory disorders. In addition, we also showed that the prevalence of cognitive difficulties is higher in COVID-19 patients with olfactory disorders than in those without. Furthermore, cognitive difficulties in patients with long-term olfactory disorders are more strongly associated with memory difficulties than with attention difficulties. Finally, mood disorders were more frequent in COVID-19 participants with olfactory loss than in those without.<br><br>CONCLUSION: Taken together, these data suggest that in COVID-19, the duration of olfactory loss is a key factor, strongly associated with cognitive and affective impairment. These data should provide us with further guidance on the management of people affected, which should not simply be unimodal, targeting just one category of symptoms.},
}
@article {pmid41108810,
year = {2025},
author = {Sharma, D and Kamm, CP and Hoepner, R and Penner, IK and Nyffeler, T and Diem, L},
title = {Characterizing post-COVID-19 syndrome in multiple sclerosis: Vaccine status, infection burden, and therapy categories as predictors.},
journal = {Multiple sclerosis and related disorders},
volume = {104},
number = {},
pages = {106792},
doi = {10.1016/j.msard.2025.106792},
pmid = {41108810},
issn = {2211-0356},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Female ; Male ; *Multiple Sclerosis/drug therapy/epidemiology/complications ; Cross-Sectional Studies ; Adult ; Middle Aged ; COVID-19 Vaccines ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Immunosuppressive Agents/therapeutic use ; },
abstract = {BACKGROUND: Post-COVID-19 syndrome (PCS) is a significant long-term complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, yet its prevalence and risk factors in people with multiple sclerosis (pwMS) under disease-modifying therapies (DMTs) remain underexplored.<br><br>OBJECTIVE: This study aimed to characterize the clinical course of coronavirus disease 2019 (COVID-19) and identify predictors of PCS in pwMS, focusing on vaccination status, infection severity and frequency, and DMT categories.<br><br>METHODS: In this cross-sectional study, 107 pwMS from two centers completed a survey assessing COVID-19 history, persistent symptoms, immunotherapy, and vaccination status. PCS was defined as symptoms persisting >12 weeks after infection. Participants were stratified by DMT categories, infection number, and vaccination status.<br><br>RESULTS: Of 107 participants, 7 (6.5 %) reported PCS. The most frequent symptoms were fatigue (71.4 %), pain (57.1 %), and headache (42.9 %). Patients with PCS had a higher mean number of SARS-CoV-2 infections (2.1, 95 % CI: 1.3-3.0) compared to those without (1.3, 95 % CI: 1.2-1.4; p = 0.004). A significant association was found with DMT category: 71.4 % (5/7) of affected individuals were on category I therapies (Interferon/Glatiramer acetate, Dimethyl fumarate, Teriflunomide) compared to 17 % of pwMS without PCS (p < 0.001). No significant effect was observed for COVID-19 severity or vaccination status.<br><br>CONCLUSIONS: PCS prevalence in this MS cohort was lower than in the general population, but category I DMTs and repeated infections were key risk factors. Findings suggest the need for individualized risk assessment, indicating that higher efficacy DMTs do not appear to pose an increased risk of PCS in pwMS.},
}
@article {pmid41108594,
year = {2025},
author = {Akbar, N and Phadke, S and Mehelay, S and Pullattayil, AK and Fakolade, A and Busse, M},
title = {Considerations of race and ethnicity within rehabilitation studies for post COVID-19 condition: A scoping review.},
journal = {PM &amp; R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70027},
pmid = {41108594},
issn = {1934-1563},
abstract = {Post COVID-19 condition (PCC) or long COVID disproportionately affects racial and ethnic minority communities. There are a growing number of rehabilitation studies for PCC, however, it has yet to be determined whether existing studies take race and ethnicity into account in their study designs and whether existing rehabilitative approaches are equally effective across diverse racial and ethnic groups. The objective of this study was to describe the extent to which rehabilitation studies of PCC consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, designing intervention delivery and adherence promoting approaches, selecting outcome measures, and reporting results. Of the 4845 studies screened, 23 met eligibility criteria and were included in this review. The most common reason for exclusion was a lack of mention of race or ethnicity anywhere within the article. Among the 23 studies included, 13 studies provided data on the race and/or ethnicity characteristics of their sample, with 88% of participants across all of these studies being White. Less than 25% of studies described the incorporation of race and/or ethnicity in their recruitment strategies (n = 3, 13%) or data analysis (n = 5, 22%). Greater racial and ethnic diversity is needed within rehabilitation studies for PCC as there is currently a significant underrepresentation of racial and ethnic minorities in existing studies. Overall, more PCC rehabilitation studies need to incorporate race and ethnicity into their study designs as it is not well understood whether existing rehabilitation strategies are equally effective across different racial and ethnic groups.},
}
@article {pmid41107158,
year = {2025},
author = {Rutsch, M and Deck, R},
title = {[Work-related participation restrictions of Long COVID rehabilitants over time - Findings of a qualitative study].},
journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen},
volume = {198-199},
number = {},
pages = {62-71},
doi = {10.1016/j.zefq.2025.09.004},
pmid = {41107158},
issn = {2212-0289},
mesh = {Humans ; Middle Aged ; Adult ; Female ; Male ; *COVID-19/rehabilitation/psychology ; Qualitative Research ; Aged ; Young Adult ; *Return to Work/psychology ; Adolescent ; Germany ; *Rehabilitation, Vocational/psychology ; },
abstract = {BACKGROUND: People who are affected by long COVID (LC) and have limitations in their ability to work can apply for a multi-professional rehabilitation programme. This qualitative study analysed the development of occupational participation, health limitations at work and factors supporting occupational participation in LC rehabilitants.<br><br>METHODS: Guided telephone interviews were conducted with LC rehabilitants aged 18-65 years, who were undergoing pneumological rehabilitation, at three time points (shortly after the end of rehabilitation, and six and twelve months after rehabilitation). Data were analysed using qualitative content analysis according to Mayring.<br><br>RESULTS: Between 04/2021 and 07/2022, a total of 30 interviews were conducted with 11 rehabilitants (N&#x202f;=&#x202f;7 women; average age: 50 years). Three health-related stress dimensions were identified: cognitive (e. g., word-finding difficulties, concentration problems), psychosocial (e. g., anxiety, worry), and physical (e. g., physical exhaustion, shortness of breath) limitations. The reintegration prepared by social services, the general conditions at the workplace (e. g., flexible working hours, empathy in the workplace) and personality traits, such as acceptance of personal limitations, were described as conducive to occupational participation. Respondents used compensatory techniques (e. g., mnemonics) and pacing to cope with the demands of work despite existing limitations.<br><br>CONCLUSION: The results of the study show that "returning to work" is not the same as "regaining the ability to work". In both rehabilitation and aftercare, the restoration of physical, psychosocial, and cognitive work ability should play an essential role in counteracting the manifestation of participation restrictions.},
}
@article {pmid41106819,
year = {2025},
author = {McLoughlin, C and Wang, JY and Do, F and Kanbayashi, T and Couturier, A and Carson, A and Stone, J},
title = {An Exploration of How Functional Neurological Disorder Is Discussed on X (Twitter): Mixed Methods Study Using Social Network and Content Analysis.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e73439},
pmid = {41106819},
issn = {1438-8871},
mesh = {Humans ; *Social Media ; *Nervous System Diseases/psychology ; COVID-19 ; *Social Networking ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Functional neurological disorder (FND) is one of the commonest conditions in neurological practice, describing symptoms like paralysis and seizures that can be severe and disabling. It is a diagnosis that is confirmed clinically rather than by scans or laboratory results. It is a stigmatized and widely misperceived condition, and since the emergence of long COVID, there has been some conflation of FND with other conditions, which has caused further misunderstanding. Social media has become increasingly popular for patients to learn and interact about their conditions, and the information that they seek and receive may be shaped by many factors. Prior to this study, the online discourse about FND had not been described in the literature.<br><br>OBJECTIVE: We aimed to analyze and describe how FND is discussed on the social media platform X (formerly known as Twitter) using a mixed methods approach.<br><br>METHODS: Using search terms related to FND, the authors collected data from 426 users and 1104 posts, generating a total of 7640 replies and reposts over a 2-month time frame in 2024. Quantitative descriptive and social network analyses were carried out to map key influential users and communities, in addition to measuring the influence of users. Content analysis was undertaken to describe the prevalent topics being discussed.<br><br>RESULTS: More users overall associated with conditions outside FND (n=180, 42.3%), mostly long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, compared with FND (n=148, 34.7%). Self-declared patients made up 40.8% (450/1104) of posts and 36.4% (n=155) of users. Social network analysis revealed 2 separate communities with little interaction. There was a prominence of myalgic encephalomyelitis/chronic fatigue syndrome and long COVID-associated users (nodes) over FND users (nodes). The former cluster showed stronger connections outwardly or peripherally than the FND cluster, suggesting that they may have a stronger impact on shaping the public narrative around FND than FND nodes. In total, 7 of the top 10 most influential users&#xa0;often displayed anti-FND views, while&#xa0;FND organizations and professionals had much less influence. There were 58 posts with at least 5000 views. Of these 58, 10 were from self-declared FND professionals, while 19 were from self-declared professionals associated with other conditions. Of these highly viewed posts, 38 of 58 were negatively predisposed toward FND. Content analysis showed themes of (1) conflict, (2) deception, (3) mistreatment and harm, (4) symptom experience, (5) knowledge, and (6) support.<br><br>CONCLUSIONS: A large proportion of the discourse around FND on X is shaped by users who are dismissive of the concept of FND and those associated with it. These findings have implications for individuals getting support for a condition that is already widely misunderstood. This study could provide a template for assessing how other&#xa0;stigmatized conditions are perceived on the web.},
}
@article {pmid41105680,
year = {2025},
author = {Catalfamo, CJ and Jacobs, ET and Falk, LP and Lauro, P and Ernst, KC and Farland, LV and Heslin, KM and Pogreba-Brown, K and Garcia-Filion, PC},
title = {Concordance between self-reported SARS-CoV-2 positivity and laboratory-confirmed positivity.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0334102},
pmid = {41105680},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/diagnosis/epidemiology/virology ; *Self Report ; Middle Aged ; Male ; Adult ; Female ; *SARS-CoV-2/isolation &amp; purification ; Aged ; Arizona/epidemiology ; Young Adult ; Adolescent ; COVID-19 Testing ; },
abstract = {As the use and availability of at-home antigen tests for SARS-CoV-2 infection have increased, the number of individuals with SARS-CoV-2 infections that are reported to state COVID-19 surveillance systems have decreased. Self-reported infection dates are critical to accurately track incidence and outbreaks of COVID-19 and for continued research on illness progression; however, the reliability of self-reported infection dates is unknown to date. To assess accuracy of self-reported test dates, we utilized self-reported SARS-CoV-2 testing data from the Arizona CoVHORT Study (CoVHORT) and laboratory-confirmed testing data collected by the Arizona Department of Health Services (ADHS) and calculated the difference in days between dates to examine their percent agreement. We used logistic regression to assess if any participant characteristics were associated with self-reporting a test date >7 days different than the laboratory confirmed date. A total of 1,900 CoVHORT participants aged 18 years or older were included in our analyses. Most participants (82.5%) reported a test date within 7 days of the laboratory confirmed date of their illness. Increasing age and number of weeks between testing positive and self-reporting the test date were both significantly associated with a difference of 7 days or greater between dates. There was an 84% increase (OR=1.84, 95% CI = 1.11-3.06) in likelihood of inaccurately self-reporting their SARS-CoV-2 test date for participants aged 55 years and older and a 2% increase (OR=1.02, 95% CI = 1.02-1.03) for each elapsed week following their SARS-CoV-2 test. We observed an 82% percent agreement (dates within 7 days of each other) between self-reported and laboratory confirmed test dates, suggesting that self-reported SARS-CoV-2 test dates are sufficient for identifying and tracking Long COVID or Post-COVID Conditions when a laboratory-confirmed test date is not available. However, increasing age and greater time between test date and date of self-report were found to decrease the agreement between self-reported and laboratory confirmed test dates.},
}
@article {pmid41104805,
year = {2025},
author = {Luo, S and Lai, LY and Zhu, R and Gao, Y and Zhao, Z},
title = {Prevalence and duration of common symptoms in people with long COVID: a systematic review and meta-analysis.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04282},
pmid = {41104805},
issn = {2047-2986},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Time Factors ; Fatigue/epidemiology ; },
abstract = {BACKGROUND: During the COVID-19 pandemic, an increasing number of patients have reported persistent symptoms after recovery, a phenomenon known as long COVID. These symptoms may persist for weeks or months, affecting the patient's daily life and health. To systematically understand the long-term impact of long COVID, this study conducted a systematic review and meta-analysis. This study aims to determine the long-term effects of long COVID by identifying, evaluating and summarising the incidence and duration of persistent symptoms after the acute phase of COVID-19.<br><br>METHOD: We searched PubMed, Embase, and medRxiv up to August 2021 for articles and preprints presenting original research on the symptoms of long COVID. Following title/abstract and full-text screening, based on the PICOS framework, we excluded articles that did not clearly report on diagnoses, reported on symptoms lasting less than four weeks, lacked epidemiological data, or did not provide complete data. We assessed the bias of included studies using the Newcastle-Ottawa Scale. For effects reported in more than two studies, we performed meta-analysis of prevalence, and also counted the duration of each symptom.<br><br>RESULTS: We included 19 observational studies in the meta-analysis, through which we determined the incidence and duration of five common long COVID symptoms, including cognitive/memory/attention disorders (36%, unreported duration), fatigue (34%, 5.5 months), mental health problems (including anxiety and depression, 31%, 3.5-3.8 months), and dyspnoea (24%, 6.52 months) and chest pain (23%, 2 months).<br><br>CONCLUSIONS: The symptoms of long COVID usually persist after the acute phase of COVID-19. The clustering of long COVID symptoms provides a direction for studying the aetiology, diagnosis, and management of post-COVID conditions. Our findings provide important baseline data for the prevention and treatment of long COVID.},
}
@article {pmid41101206,
year = {2026},
author = {January, J and Zwaenepoel, O and Sanga, N and Gettemans, J and Iwuoha, E},
title = {High sensitivity perovskite-tagged nanobody electrochemiluminescent immunosensor for spike (S1) protein biomarker-based persistent viral reservoir detection.},
journal = {Bioelectrochemistry (Amsterdam, Netherlands)},
volume = {168},
number = {},
pages = {109137},
doi = {10.1016/j.bioelechem.2025.109137},
pmid = {41101206},
issn = {1878-562X},
mesh = {*Spike Glycoprotein, Coronavirus/analysis/immunology ; Humans ; *COVID-19/diagnosis/virology ; *SARS-CoV-2/isolation &amp; purification/immunology ; *Single-Domain Antibodies/chemistry/immunology ; *Biosensing Techniques/methods ; *Titanium/chemistry ; Immunoassay/methods ; *Electrochemical Techniques/methods ; *Oxides/chemistry ; Luminescent Measurements/methods ; *Calcium Compounds/chemistry ; Biomarkers/analysis ; Limit of Detection ; Animals ; },
abstract = {Persistent viral reservoirs (PVR) of SARS-CoV-2 (or long COVID-19) and latent COVID-19 disease have been of great concern to clinicians. Several studies have identified spike protein (S1) as a definitive biomarker for the early detection of persistent viral reservoirs and latent COVID-19. A novel sandwich-format electrochemical immunosensor integrating a nanocomposite material was engineered for rapid and sensitive latent COVID-19 detection. The platform structure, AuSPE||strep|Nb1|BSA|biotin|S1|strep-LiSmZrO3-Nb2 + BSA (AuSPE = gold screen-printed electrode, strep = streptavidin-thiol, Nb1 = primary nanobody, Nb2 = secondary nanobody, BSA = bovine serum albumin, and spike (S1) protein = S1), featured a disposable AuSPE modified with strep to anchor a biotinylated camelid Nb1 specific to the spike protein. A Nb2 conjugated to streptavidin-labelled LiSmZrO3 perovskite completed the sandwich complex, enhancing both affinity and signal transduction. Electrochemical responses of the sensor were studied via electrochemiluminescent (ECL) signal transduction. The S1-sensitive sandwich immunosensor had a detection range of 0-1000 pg mL[-1] with a limit of detection of 0.04 pg mL[-1] via ECL. As feasibility studies, commercial spike protein in buffered solutions and human serum, highlighting the potential for the immunosensor to be used in SARS-CoV-2 patients and PVRs. The nanobody sandwich immunosensor showed excellent stability, selectivity, sensitivity, and reproducibility. The immunosensor serves as a broad PVR for a SARS-CoV-2 screening tool, detecting elevated S1 levels to enable early, targeted diagnostics.},
}
@article {pmid41101103,
year = {2025},
author = {Adebisi, YA and Ogunkola, IO and Jimoh, ND and Alshahrani, NZ and Shomuyiwa, DO and Alaran, AJ and Lucero-Prisno, DE},
title = {Tobacco smoking and the risk of Long COVID: a prospective cohort study with mediation analysis.},
journal = {Journal of epidemiology and population health},
volume = {73},
number = {5},
pages = {203142},
doi = {10.1016/j.jeph.2025.203142},
pmid = {41101103},
issn = {2950-4333},
mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology ; Middle Aged ; Prospective Studies ; Adult ; *Tobacco Smoking/epidemiology/adverse effects ; United Kingdom/epidemiology ; Risk Factors ; Longitudinal Studies ; Mediation Analysis ; Aged ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Tobacco smoking is a well-established risk factor for severe acute COVID-19 outcomes, but evidence regarding its role in Long COVID is limited and inconsistent. This study investigated whether pre-pandemic smoking independently predicted Long COVID and assessed mediation by long-standing illness or disability in a nationally representative cohort.<br><br>METHODS: We analysed data from Waves 10 (2018-19) and 14 (2022-23) of the UK Household Longitudinal Study. Smoking status (current vs non-smoker) and covariates (age, sex, education, income satisfaction, ethnicity, rural/urban residence) were measured at baseline (Wave 10). Long COVID, defined as symptoms lasting &#x2265;12 weeks following initial COVID-19 infection, was assessed at follow-up (Wave 14). Logistic regression was used to estimate the total association between smoking and Long COVID. We then applied generalized structural equation modelling and parametric causal mediation analysis, specifying long-standing illness or disability at baseline as the mediator.<br><br>RESULTS: Among 11,944 participants, 1097 (9.2 %) reported Long COVID symptoms at follow-up. In the unadjusted model, smoking was associated with increased odds of Long COVID (odds ratio [OR] = 1.22, 95 % CI: 1.00-1.48, p = 0.05), although this was only borderline significant. After adjusting for demographic and socioeconomic factors, the association was no longer statistically significant (adjusted OR = 1.11, 95 % CI: 0.91-1.35, p = 0.32). The structural equation model indicated that smoking was associated with higher likelihood of long-standing illness or disability at baseline (&#x3b2; = 0.461, 95 % CI: 0.33-0.59, p <0.001, log-odds scale), which in turn predicted Long COVID (&#x3b2; = 0.435, 95 % CI: 0.30-0.57, p <0.001, log-odds scale). Mediation analysis revealed a small but statistically significant indirect effect of smoking on Long COVID operating through long-standing illness or disability (risk difference = 0.0057, 95 % CI: 0.0020-0.0095, p = 0.003), but no significant direct effect (risk difference = 0.0027, 95 % CI: -0.0144 to 0.0199, p = 0.76).<br><br>CONCLUSION: Smoking did not independently predict Long COVID, but may increase vulnerability indirectly through pre-existing long-standing illness or disability.},
}
@article {pmid41099164,
year = {2026},
author = {Chate, RC and Carvalho, CRR and Sawamura, MVY and Salge, JM and Fonseca, EKUN and Amaral, PTMA and de Almeida Lamas, C and de Luna, LAV and Kay, FU and Junior, ANA and Nomura, CH},
title = {Quantitative Chest Computed Tomography and Machine Learning for Subphenotyping Small Airways Disease in Long COVID.},
journal = {Journal of thoracic imaging},
volume = {41},
number = {2},
pages = {},
doi = {10.1097/RTI.0000000000000861},
pmid = {41099164},
issn = {1536-0237},
mesh = {Humans ; Male ; Middle Aged ; *COVID-19/diagnostic imaging/complications/physiopathology ; Female ; *Tomography, X-Ray Computed/methods ; *Machine Learning ; Retrospective Studies ; Cross-Sectional Studies ; Lung/diagnostic imaging/physiopathology ; Aged ; Adult ; SARS-CoV-2 ; Phenotype ; },
abstract = {PURPOSE: To investigate imaging phenotypes in posthospitalized COVID-19 patients by integrating quantitative CT (QCT) and machine learning (ML), with a focus on small airway disease (SAD) and its correlation with plethysmography.<br><br>MATERIALS AND METHODS: In this single-center cross-sectional retrospective study, a subanalysis of a larger prospective cohort, 257 adult survivors from the initial COVID-19 peak (mean age, 56&#xb1;13&#xa0;y; 49% male) were evaluated. Patients were admitted to a quaternary hospital between March 30 and August 31, 2020 (median length of stay: 16 [8-26] d) and underwent plethysmography along with volumetric inspiratory and expiratory chest CT 6 to 12 months after hospitalization. QCT parameters were derived using AI-Rad Companion Chest CT (Siemens Healthineers).<br><br>RESULTS: Hierarchical clustering of QCT parameters identified 4 phenotypes among survivors, named "SAD," "intermediate," "younger fibrotic," and "older fibrotic," based on clinical and imaging characteristics. The SAD cluster (n=37, 14%) showed higher residual volume (RV) and RV/total lung capacity (TLC) ratios as well as lower FEF 25-75 /forced vital capacity (FVC) on plethysmography. The older fibrotic cluster (n=42, 16%) had the lowest TLC and FVC values. The younger fibrotic cluster (n=79, 31%) demonstrated lower RV and RV/TLC ratios and higher FEF 25-75 than the other phenotypes. The intermediate cluster (n=99, 39%) exhibited characteristics that were intermediate between those of SAD and fibrotic phenotypes.<br><br>CONCLUSION: The integration of inspiratory and expiratory chest CT with quantitative analysis and ML enables the identification of distinct imaging phenotypes in long COVID patients, including a unique SAD cluster strongly associated with specific pulmonary function abnormalities.},
}
@article {pmid41098726,
year = {2025},
author = {Afrin, F and Zhang, Q and Alturaiki, W and Mahallawi, W},
title = {Editorial: Advances in understanding mucosal immunity in coronaviruses: from mechanisms to vaccines.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1702286},
pmid = {41098726},
issn = {1664-3224},
}
@article {pmid41097103,
year = {2025},
author = {Lesgards, JF and Cerdan, D and Perronne, C},
title = {Correction: Lesgards et al. Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways? Int. J. Mol. Sci. 2025, 26, 7879.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41097103},
issn = {1422-0067},
abstract = {In the original publication [...].},
}
@article {pmid41096962,
year = {2025},
author = {László, N and Mărginean, C and Mátyás, BB and Man, CA and Nagy, EE and Jimborean, G},
title = {Macrophage Migration Inhibitory Factor and Post-Discharge Inflammatory Profiles in Severe COVID-19: A Prospective Observational Study from Romania.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41096962},
issn = {1422-0067},
mesh = {Humans ; *Macrophage Migration-Inhibitory Factors/blood ; *COVID-19/blood/immunology/pathology ; Female ; Romania/epidemiology ; Male ; Middle Aged ; Prospective Studies ; Aged ; Adult ; Cytokines/blood ; *Inflammation/blood ; SARS-CoV-2 ; Severity of Illness Index ; Patient Discharge ; Tumor Necrosis Factor-alpha/blood ; Intramolecular Oxidoreductases ; },
abstract = {Dysregulated cytokine responses are a hallmark of severe COVID-19; however, the persistence of these responses following hospital discharge remains inadequately understood. This study aimed to characterize the inflammatory profile of hospitalized COVID-19 patients in Mureș County, Romania, at the point of admission and one month post-discharge. We conducted a prospective observational study involving 68 patients with RT-PCR-confirmed SARS-CoV-2 infection, classified according to disease severity. Blood samples were collected at baseline and after one month. Macrophage migration inhibitory factor (MIF) levels were quantified using ELISA, while other cytokines, including MCP-1, IP-10, IFN-γ, IL-4, IL-10, IL-13, IL-17, and TNF-α, were measured via Luminex multiplex assays. Patients with severe disease exhibited significantly elevated levels of MIF, IFN-γ, IL-17, and TNF-α at admission (p < 0.0001). Although cytokine concentrations generally declined over time, patients with severe disease continued to display persistently elevated MIF (mean 31,035 pg/mL), IFN-γ, and TNF-α, indicative of ongoing inflammatory processes. Clinical parameters such as respiratory rate and oxygen saturation correlated with disease severity. These findings suggest that severe COVID-19 induces a prolonged inflammatory response, with MIF and IFN-γ remaining elevated beyond the acute phase. Cytokine profiling holds potential for improving prognostic assessments and identifying patients at risk of long-term immune dysregulation, with MIF emerging as a potential candidate marker for immune recovery and a possible target for therapy.},
}
@article {pmid41095969,
year = {2025},
author = {Zhou, LM and Duncan, EH and Boelig, RC and Costanzo, M and Currier, JR and Bergmann-Leitner, ES},
title = {Whole-Blood Cellular Responses: A Promising Indicator of SARS-CoV-2 Immunity Compared to Serology.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
pmid = {41095969},
issn = {2077-0383},
support = {PR211676//Congressionally Directed Medical Research Programs/ ; },
abstract = {Background: Currently available immunological tests for SARS-CoV-2 assess only antibody responses. Despite the growing evidence that T cells play a crucial role in protection, especially against emerging viral variants, no routine test is available to determine T cell immunity. The prognostic value of SARS-CoV-2-specific antibodies for determining whether individuals are immune and protected against disease remains uncertain. This is in part due to the following: (a) specificity and limitations such as the sensitivity of antibody tests, and (b) the lack of correlation between antibody titers (quantity) and the antiviral function of antibodies (quality). Approximately a quarter of SARS-CoV-2-infected patients with symptoms fail to show seroconversion in serological assays. Methods: The current report describes the development and application of a whole-blood-based assay to detect previous exposure to SARS-CoV-2. Whole blood is stimulated with SARS-CoV-2-derived peptides identified during assay development and stimulation-induced cytokines quantified using a multiplex testing platform. The resulting cytokine profiles are generated using computational tools to identify previous exposure to the virus. Results: The application of the assay revealed a lack of self-awareness of individuals' COVID-19 infection history and demonstrated the value of this new assay to assess the prevalence of SARS-CoV-2 exposure history and immunity in populations. Conclusions: Positive responses in this assay can facilitate the identification of underlying causes of unexplained symptoms and provide clinically actionable insights for healthcare applications, including in the continued conundrum of post-acute sequela of SARS-CoV-2 infection (PASC or "long COVID"), for which both diagnosis and management remain challenging.},
}
@article {pmid41094377,
year = {2025},
author = {Arab, Z and Shayanfar, N and Mojaver, MR and Khormali, M and Boskabady, MH and Niazmand, S},
title = {Cardiopulmonary crosstalk in Long COVID: a systematic review of emerging evidence.},
journal = {BMC cardiovascular disorders},
volume = {25},
number = {1},
pages = {742},
pmid = {41094377},
issn = {1471-2261},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Endothelium, Vascular/physiopathology ; *Pulmonary Fibrosis/physiopathology ; },
abstract = {BACKGROUND: Long COVID is a complex, multisystem syndrome with significant cardiopulmonary implications. Persistent inflammation, endothelial dysfunction, and microvascular injury contribute to prolonged symptoms such as dyspnea, chest pain, and exercise intolerance. Despite growing recognition of these complications, the underlying mechanisms of cardiopulmonary interactions remain poorly understood.<br><br>METHODS: A comprehensive literature search was conducted on PubMed, Scopus, Google Scholar, and Web of Science covering studies from 2019 to 2025. Keywords included "Long COVID", "cardiopulmonary interaction", "pulmonary fibrosis", "myocardial inflammation", and "endothelial dysfunction". A total of 102 articles were included, comprising 65 original research studies and 37 review articles.<br><br>RESULTS: Pulmonary sequelae, such as fibrotic remodeling, persistent hypoxia, and microthrombosis, impose significant strain on the cardiovascular system, exacerbating myocardial inflammation, arrhythmias, and endothelial dysfunction. Shared mechanisms, such as oxidative stress, immune dysregulation, and neurohumoral activation, create a vicious cycle of sustained cardiopulmonary impairment. The disruption of the renin-angiotensin-aldosterone system (RAAS) further contributes to systemic vascular dysregulation.<br><br>CONCLUSION: A deeper understanding of cardiopulmonary interactions in Long COVID is essential for developing effective management strategies. Targeting inflammatory pathways, restoring endothelial function, and addressing autonomic instability may provide therapeutic benefits. As the long-term impact of this syndrome continues to evolve, further research is needed to refine treatment approaches and mitigate its burden on global health.},
}
@article {pmid41092189,
year = {2025},
author = {Silva, AS and Dornelas, R and Silva, JRLE},
title = {Long COVID: persistent impacts and challenges for speech-language-hearing therapy.},
journal = {CoDAS},
volume = {37},
number = {5},
pages = {e20240291},
pmid = {41092189},
issn = {2317-1782},
}
@article {pmid41091675,
year = {2025},
author = {Nagra, G and Ezeugwu, VE and Bostick, GP and Branton, E and Dennett, L and Drake, K and Durand-Moreau, Q and Guptill, C and Hall, M and Ho, C and Hung, P and Khan, A and Lam, GY and Nowrouzi-Kia, B and Gross, DP},
title = {Return-to-work for people living with long COVID: A scoping review of interventions and recommendations.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0321891},
pmid = {41091675},
issn = {1932-6203},
mesh = {Humans ; *Return to Work ; *Post-Acute COVID-19 Syndrome/complications/rehabilitation ; },
abstract = {INTRODUCTION: Long COVID is characterized by the presence of new onset or persistent symptoms 3 months after a suspected or confirmed history of SARS-CoV-2 infection. It is a complex and multi-faceted condition that affects people in different ways. Long COVID affects individuals' labour market participation. While some cannot work, others may return to work (RTW) in a limited capacity. Determining what rehabilitation or related strategies are safe and effective for facilitating RTW is necessary.<br><br>OBJECTIVES: To synthesize evidence on RTW interventions for people living with Long COVID and to identify 'promising' interventions for enhancing work ability and RTW.<br><br>METHODS: We followed Arksey &amp; O'Malley's methodology and the PRISMA extension for scoping reviews. Five electronic bibliographic databases and grey literature were searched. The literature search included various study designs, such as randomized controlled trials (RCT), quasi-experimental designs, and observational studies as well as clinical practice guidelines (CPGs). Two reviewers conducted screening and data extraction, with disagreements resolved through consensus. Intervention studies were categorized as promising (statistically significant RTW outcomes or &#x2265; 50% RTW), somewhat promising (20% to < 50% RTW), not promising (non-statistically significant RTW outcomes or < 20% RTW), or uncertain (did not specify proportion of RTW).<br><br>RESULTS: Twelve CPGs and nineteen intervention studies were identified. Of the intervention studies, 5 were cohort studies, 3 quasi-experimental studies, 4 observational, 2 interventional, 3 RCTs, and 2 case reports. Promising interventions included multimodal and interdisciplinary work-focused rehabilitation, multidisciplinary inpatient and outpatient rehabilitation, psychoeducation, pacing, and breathing strategies, shifting focus from symptom monitoring to optimizing functional outcomes, enhanced external counterpulsation inflatable pressure to improve blood flow, and constraint-induced cognitive therapy.<br><br>CONCLUSION: Many uncertainties remain regarding which RTW interventions are effective or the optimal characteristics of these interventions.},
}
@article {pmid41089957,
year = {2025},
author = {Begum, S and Mirghani, HO and Alhowiti, A and Alrasheed, T and Sulaiman, AHA},
title = {Prevalence and risk factors for post-COVID-19 syndrome on medical students in Tabuk, Saudi Arabia-2023-2024.},
journal = {Journal of family medicine and primary care},
volume = {14},
number = {9},
pages = {3729-3734},
pmid = {41089957},
issn = {2249-4863},
abstract = {BACKGROUND: COVID-19 has infected 221 million individuals worldwide and new strains are discovered continuously. An important complication is the post-COVID-19 syndrome that affects various organs with substantial morbidities. Studies on post-COVID-19 symptoms and risk factors are scarce. We aimed to assess the same among medical students at the University of Tabuk, Saudi Arabia.<br><br>METHODOLOGY: This cross-sectional study was conducted among 424 medical students at the University of Tabuk, Saudi Arabia, during the period from July 2023 to October 2024. A web-based questionnaire detailing the demographic factors, post-COVID-19 symptoms, comorbidities, vitamin D deficiency, and the cumulative grade average (GPA) was used.<br><br>RESULTS: Out of the 424 students, 38.2% were overweight and 9.4% were obese, 26.9% had bronchial asthma, and diabetes was found in 11.8%. Smoking was observed in 25%, and 58.5% were vitamin D deficient, while 22.6% were hospitalized with COVID-19. The majority of students received > two doses (74.1%), 24.5% received two doses, and 1.4% received one dose. The majority (80.7%) of students reported at least one post-COVID-19 symptom, and headache was the commonest symptom (63.7%), followed by cough in 50.5%. The absence from classrooms was 54.2%, 32.1%, and 13.7% (3 days, 3-8 days, and >10 days/month, respectively), and 44.8% thought that long COVID-19 negatively affected their GPA.<br><br>CONCLUSION: Post-COVID-19 syndrome was associated with diabetes, bronchial asthma, and vitamin D deficiency, odd ratios, 95% CI, 0.011-0.910, 0.005-0.312, 0.203-0.821, respectively, P values > 0.05. No significant association was found regarding, age, gender, and smoking, P values >0.05.},
}
@article {pmid41089587,
year = {2025},
author = {Albazee, E and Alajmi, SA and Alkandari, AM and Aladwani, AN and Alenezi, YY and Alsaeed, MA and Uqlah, B and Abu-Zaid, A},
title = {Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e94386},
pmid = {41089587},
issn = {2168-8184},
abstract = {A notable rise in olfactory dysfunction (OD) prevalence has been observed since the COVID-19 pandemic. COVID-19-related OD is associated with several consequences, especially deteriorated quality of life. Hence, several treatment options have been investigated, with platelet-rich plasma (PRP) showing promising results. A systematic review and meta-analysis summarizing randomized controlled trial (RCT) evidence were retrieved from PubMed, Google Scholar, Scopus, and Web of Science up to June 2025. The risk of bias was assessed using the Cochrane Risk of Bias 2 assessment tool. Data were analyzed using Stata MP version 18 (StataCorp LLC, College Station, TX), pooling dichotomous outcomes as relative risks (RRs) and continuous outcomes as standardized mean differences (SMDs), each with 95% confidence intervals (CIs). Four RCTs, including 198 participants, were included in our meta-analysis. PRP significantly improved objective olfactory scores (SMD = 1.86, 95% CI (0.14, 3.57), p = 0.03) and subjective olfactory scores (SMD = 0.92, 95% CI (0.32, 1.51), p < 0.001). Additionally, PRP significantly increased the response rate (RR = 1.79, 95% CI (1.14, 2.81), p = 0.01). PRP was generally well-tolerated across the included trials, with no major adverse events reported. Two RCTs showed an overall low risk of bias, one trial showed some concerns, and another showed a high risk of bias. With uncertain evidence, PRP may improve both objective and subjective smell function and clinical outcomes in people with long COVID-related OD. PRP treatment was reported to be safe, with minor, temporary side effects primarily related to the procedure. Although initial results are promising, the small number of RCTs requires a cautious approach to interpretation.},
}
@article {pmid41089328,
year = {2025},
author = {Blitshteyn, S and Funez-dePagnier, G and Szombathy, A and Hutchinson, M},
title = {Immunotherapies for postural orthostatic tachycardia syndrome, other common autonomic disorders, and Long COVID: current state and future direction.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1647203},
pmid = {41089328},
issn = {2235-2988},
mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/therapy/immunology ; *COVID-19/therapy/immunology/complications ; *Immunotherapy/methods/trends ; *Autonomic Nervous System Diseases/therapy/immunology ; Immunoglobulins, Intravenous/therapeutic use ; SARS-CoV-2 ; Plasmapheresis ; Adrenal Cortex Hormones/therapeutic use ; Post-Acute COVID-19 Syndrome ; },
abstract = {Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope, and orthostatic hypotension are the most common autonomic disorders encountered in clinical practice. The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. However, the treatment of common autonomic disorders has traditionally included pharmacologic and non-pharmacologic symptomatic therapies as the standard approach. Unfortunately, these symptomatic therapies have been of limited or insufficient efficacy to meaningfully improve functional status or result in recovery, especially in patients with severe symptoms. Case reports, case series, and clinical experience suggest that intravenous and subcutaneous immunoglobulin, as well as other immunologic therapies (such as plasmapheresis, corticosteroids, and rituximab), may be effective in some patients with severe POTS and other common autonomic disorders who are refractory to standard therapies. In this narrative review, we summarize the literature available on the topic of immunotherapies for POTS, other common autonomic disorders, and Long COVID. We also highlight the need for large, multicenter, placebo-controlled trials of immunoglobulin, plasmapheresis, intermittent corticosteroids, and other repurposed immunotherapies in patients with common autonomic disorders who have significant functional impairment.},
}
@article {pmid41088275,
year = {2025},
author = {Portela, MC and Escosteguy, CC and Lima, SML and Bernardino, M and do Nascimento Caldas, B and Soares, L and de Vasconcellos, MTL and Martins, M and de Andrade, CLT and Baginski, NP and Góes, G and Sabaine, B and Cavalcanti, M and Furtado, D and Stelson, E and Cornish, F and Aveling, EL},
title = {Healthcare gaps and inequities following hospitalisation for COVID-19 in Brazil's universal healthcare system: a patient-engaged survey of Long COVID healthcare needs, use and barriers.},
journal = {International journal for equity in health},
volume = {24},
number = {1},
pages = {275},
pmid = {41088275},
issn = {1475-9276},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/therapy/epidemiology ; Female ; Male ; Middle Aged ; Adult ; *Health Services Accessibility/statistics &amp; numerical data ; *Hospitalization/statistics &amp; numerical data ; *Healthcare Disparities/statistics &amp; numerical data ; SARS-CoV-2 ; *Health Services Needs and Demand/statistics &amp; numerical data ; Surveys and Questionnaires ; Aged ; *Universal Health Care ; Young Adult ; Cohort Studies ; Adolescent ; },
abstract = {BACKGROUND: Long COVID (LC) is an infection-associated chronic condition (IACC) that tends to be neglected by healthcare systems. Studies of post-COVID healthcare utilisation find elevated levels of use but have mainly been conducted in high-income settings. In the context of Brazil's universal health system (SUS), our patient-engaged study aimed to map healthcare needs, use, and access barriers related to LC up to 24 months following COVID-19 hospitalisation, in the interest of informing health system planning for an equitable LC response.<br><br>METHODS: A cohort survey included a probabilistic sample of hospitalised COVID-19-confirmed individuals aged&#x2009;&#x2265;&#x2009;18, who had been discharged from public hospitals in Rio de Janeiro between December 2020 and November 2022. Socio-demographic and clinical data were collected, including self-reported LC symptoms, self-reported LC, healthcare needs, use, and access barriers.<br><br>RESULTS: In a sample of 556 participants, corresponding to an estimated population of 11,328 individuals, 50.0% (95%CI 44.3-55.6%) reported healthcare needs in the six months prior, due to new-onset or worsened conditions after COVID-19. Almost 45.0% did not complete high school, while 26.5% lived below the poverty line (~&#x2009;US$6.85 per day), indicating a high proportion of socially vulnerable individuals. High prevalence of LC symptoms, self-reported LC, and new diagnoses were observed. Healthcare needs were associated with acute disease severity, number of LC symptoms, and new post-COVID diagnoses, including cardiovascular and kidney diseases, and endocrine and musculoskeletal disorders. Significant gaps existed between need and access to services, and part of the access to services involved substantial out-of-pocket expenditure. These gaps were particularly pronounced for specialised medical services, scans/imaging, post-COVID rehabilitation services, and mental healthcare. Despite a universal health system, those with higher monthly incomes (above R$1,500 or&#x2009;~&#x2009;US$250) were more likely to have accessed specialised medical care.<br><br>CONCLUSIONS: The SUS is not meeting the high need for LC healthcare, raising concerns about deepening health inequities. In Brazil, as elsewhere, LC joins other IACCs in becoming an invisibilised epidemic, with LC patients, especially those unable to pay for care, neglected amid general healthcare backlogs. A comprehensive pandemic response must include dedicated efforts to surveil and treat the long-term impacts of infection.},
}
@article {pmid41087378,
year = {2025},
author = {Yonker, LM and Dredge, D and Munro, A and Di Chiara, C and Cotugno, N and Buonsenso, D},
title = {The second-order effects that the COVID-19 pandemic has had on pediatric populations.},
journal = {Expert review of anti-infective therapy},
volume = {23},
number = {10},
pages = {997-1009},
doi = {10.1080/14787210.2025.2575044},
pmid = {41087378},
issn = {1744-8336},
support = {R01 HL173059/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/immunology/therapy ; Child ; Adolescent ; Systemic Inflammatory Response Syndrome/epidemiology ; Public Health ; Pandemics ; SARS-CoV-2 ; Autoimmune Diseases/epidemiology ; },
abstract = {INTRODUCTION: SARS-CoV-2 can have long-term health consequences that persist beyond acute infection. While this is evident in adults and the elderly, the impact on children and adolescents remains under recognized. Here we navigate the second-order post-acute effects that the COVID-19 has had on the pediatric populations, with the exception of the mental health implication of social restrictions.<br><br>AREAS COVERED: We outline common scenarios related with SARS-CoV-2 infection encountered in pediatric clinical practice, such as in the Multisystem inflammatory syndrome (MIS-C), Long Covid, neurological and autoimmune complications of Covid-19, immunological impact of the viral infection, as well as epidemiological and public health consequences associated with the implementation of non-pharmacological interventions.<br><br>EXPERT OPINION: SARS-CoV-2 has had several second-order effects on child health, from a biological, epidemiological, and public health perspective, highlighting the complexity of dealing with new infections and the urgent need to implement multidisciplinary interventions that support the health of people at single person and societal level. Funding on modern surveillance system, preventing strategies and research to better understand and cure post-acute complications of viral infections should be a priority of every funding agency.},
}
@article {pmid41087247,
year = {2025},
author = {Tanaka, H and Kubota, E and Otori, N and Mori, E},
title = {Olfactory cleft adhesion in post-COVID-19 olfactory dysfunction.},
journal = {European annals of otorhinolaryngology, head and neck diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.anorl.2025.09.004},
pmid = {41087247},
issn = {1879-730X},
abstract = {Post-COVID-19 olfactory dysfunction (PCOD) typically resolves within weeks to months; however, persistent cases exist in approximately 10% of patients beyond a year. This study investigated the role of olfactory cleft adhesions in prolonged PCOD and evaluated surgical intervention as a treatment option. Four cases of PCOD unresponsive to medical therapy underwent endoscopic sinus surgery (ESS) to address bilateral olfactory cleft obstruction identified on computed tomography (CT) scan. Adhesions between the superior/middle turbinates and nasal septum were surgically divided, and silicone plates were inserted to prevent reattachment. All patients reported significant subjective improvements in olfaction within one week of silicone removal. Objective olfactory test scores continued to improve over subsequent months, and postoperative CT scan confirmed improved ventilation of the olfactory cleft. These findings suggest that adhesions formed during inflammatory healing contribute to conductive olfactory dysfunction in Long-COVID cases, distinct from sensorineural or central OD. Surgical intervention may be beneficial for carefully selected patients with PCOD persisting for at least one year, anosmia or severe olfactory loss confirmed by testing, and CT evidence of olfactory cleft obstruction. However, the risks such as mucosal damage and potential worsening or no improvement of OD should be discussed thoroughly. Individualized treatment strategies are recommended, and further studies are warranted to optimize management of persistent PCOD.},
}
@article {pmid41086513,
year = {2025},
author = {Grafström, T and Barros, GWF and Persson, IL and Sundh, J and Forsell, MNE and Ahlm, C and Månsson, E and Tevell, S and Lind, A and Normark, J and Cajander, S},
title = {Post COVID-19 condition phenotypes: A prospective cohort study identifying four symptom clusters and their impact on long-term outcomes.},
journal = {Journal of infection and public health},
volume = {18},
number = {12},
pages = {102994},
doi = {10.1016/j.jiph.2025.102994},
pmid = {41086513},
issn = {1876-035X},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cluster Analysis ; Cognitive Dysfunction ; *COVID-19/complications/epidemiology ; Dyspnea/epidemiology ; Fatigue/epidemiology/etiology ; Hospitalization ; Phenotype ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prospective Studies ; Quality of Life ; SARS-CoV-2 ; Sweden/epidemiology ; },
abstract = {BACKGROUND: Current evidence indicates that Post COVID-19 Condition (PCC) is multifaceted with distinct phenotypes. While previous studies have identified symptom clusters-commonly featuring fatigue, respiratory symptoms, and cognitive impairment-findings have been inconsistent, and no clear consensus exists. Moreover, how these symptom clusters evolve over time, particularly beyond the first year post-infection, remains poorly understood.<br><br>METHODS: This multicentre prospective cohort study included 470 hospitalised and non-hospitalised adult individuals from the CoVUm study across four sites in Sweden between 2020 and 2021. Follow-ups were conducted up to 3 years after infection to assess persistent symptoms, health-related quality of life (HRQoL), and work capacity. Symptom clusters at 6 months were identified via hierarchical cluster analysis, and participants were tracked using a k-nearest neighbour algorithm.<br><br>RESULTS: The most common symptoms at 6 months were fatigue (33&#x202f;%), dyspnoea (32&#x202f;%), mental fatigue (30&#x202f;%), and concentration difficulties (28&#x202f;%), with a median EQ-5D-5L index of 0.98 (IQR 0.93-1). Four distinct symptom clusters were identified: (i) "Few Symptoms" (n&#x202f;=&#x202f;265, 57&#x202f;%), (ii) "Respiratory Symptoms" (n&#x202f;=&#x202f;66, 14&#x202f;%), (iii) "Neurocognitive Symptoms" (n&#x202f;=&#x202f;75, 16&#x202f;%), and (iv) "Multisystem Symptoms" (n&#x202f;=&#x202f;52, 11&#x202f;%). Participants in the latter three clusters were older, had more comorbidities, and were more often hospitalised during primary COVID-19 infection. These clusters also had significantly lower HRQoL compared to the "Few Symptoms" cluster. Over time, more than half of participants transitioned to a cluster with fewer or no symptoms, with significant perceived HRQoL improvement in the "Multisystem Symptoms" cluster.<br><br>CONCLUSION: While many patients with PCC improved over time, a subset had persistent symptoms at 3 years, especially if primary infection required hospitalisation. The identification of symptom clusters and their trajectories over time contributes to a better understanding of PCC heterogeneity, ultimately bringing the field closer to consensus on the classification and long-term impact of PCC.},
}
@article {pmid41085647,
year = {2025},
author = {Kippenbroek, N and Stölting, A and Schröder, D and Wetzke, M and Happle, C and Dopfer, C and Schmachtenberg, T and Witte, T and Steffens, S and Mikuteit, M and Müller, F and Behrens, GMN and Dopfer-Jablonka, A},
title = {[Inflammatory rheumatic diseases in patients with post-COVID syndrome].},
journal = {Zeitschrift fur Rheumatologie},
volume = {},
number = {},
pages = {},
pmid = {41085647},
issn = {1435-1250},
abstract = {BACKGROUND: The post-COVID syndrome (PCS) describes long-lasting symptoms after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PCS and rheumatic diseases, especially collagenoses, show strong overlap of symptoms and biomarkers. Thus far, no biomarkers that differentiate between PCS patients with and without rheumatic diseases exist, and data on the prevalence of rheumatic diseases in this collective in Germany is scarce.<br><br>METHOD: Based on the online platform DEFEAT-Corona, 80 people with PCS without a previously confirmed inflammatory rheumatic disease (IRD) and interest in a rheumatological evaluation were recruited. Typical complaints of PCS and rheumatic diseases were analyzed. In addition, comprehensive laboratory analyses were conducted.<br><br>RESULTS: In 6.25% (n&#x202f;=&#x2009;5) of the PCS patients,IRD was suspected or confirmed. The remaining 75 PCS patients without IRD also showed a high degree of overlap with regard to complaints typical for rheumatic disease or PCS. The inflammation parameters C&#x2011;reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly higher in PCS patients with suspected IRD compared to patients with PCS only and significantly more often exceeded normal range.<br><br>CONCLUSION: This study illustrates the high degree of overlap between PCS and rheumatic symptoms in PCS patients without previous suspicion of IRD. The risk for IRD could be elevated in PCS. However, in the view of the authors, PCS without additional risk factors, such as elevated CRP or arthritis, does not generally justify rheumatological evaluation in clinical routine. This recommendation should be further investigated in larger studies.},
}
@article {pmid41085475,
year = {2026},
author = {Stufano, A and Lucchese, G},
title = {Work Productivity Loss in People Living With Long COVID Symptoms: A Good Start and a Missed Opportunity.},
journal = {Journal of occupational and environmental medicine},
volume = {68},
number = {1},
pages = {e114},
doi = {10.1097/JOM.0000000000003584},
pmid = {41085475},
issn = {1536-5948},
}
@article {pmid41085471,
year = {2026},
author = {Naik, H and Zhang, W},
title = {Re: Work Productivity Loss in People Living With Long COVID Symptoms: A Good Start and a Missed Opportunity.},
journal = {Journal of occupational and environmental medicine},
volume = {68},
number = {1},
pages = {e113},
doi = {10.1097/JOM.0000000000003583},
pmid = {41085471},
issn = {1536-5948},
}
@article {pmid41085189,
year = {2025},
author = {Hadidchi, R and Ali, E and Piskun, H and Henry, S and Zhang, L and Duong, TQ},
title = {Elevated Risk of Long-Term Decline in Left Ventricular Ejection Fraction After COVID-19.},
journal = {Journal of the American Heart Association},
volume = {14},
number = {20},
pages = {e043976},
pmid = {41085189},
issn = {2047-9980},
mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Stroke Volume/physiology ; Aged ; *Ventricular Dysfunction, Left/physiopathology/etiology/epidemiology ; SARS-CoV-2 ; *Ventricular Function, Left/physiology ; Risk Factors ; Risk Assessment ; Time Factors ; Echocardiography ; COVID-19 Vaccines ; },
abstract = {BACKGROUND: COVID-19 has been linked to cardiovascular complications, but its long-term impact on left ventricular (LV) function is unclear. We investigated whether SARS-CoV-2 infection is associated with increased risk of LV ejection fraction (LVEF) decline and whether vaccination mitigates this risk.<br><br>METHODS: In this retrospective study, we included patients with COVID-19, normal baseline LVEF (&#x2265;50%), and at least one follow-up echocardiogram from 2016 to 2024. Outcomes were LVEF dropping <50%, 40%, and 30%. Multivariable Cox models adjusted for demographics, comorbidities, vaccination status, and baseline LVEF. Associations with acute-phase blood biomarkers were examined.<br><br>RESULTS: Among 2853 patients who were COVID+ and 3963 patients who were COVID- (baseline LVEF &#x2265;50%), patients with COVID-19 had lower mean follow-up LVEF (60.65% versus 61.53%, P<0.005) and higher rates of LVEF decline <50%, 40%, and 30%. Both hospitalized (adjusted hazard ratio [aHR], 1.57 [1.30-1.91]) and non-hospitalized (aHR, 1.48 [1.18-1.85]) patients with COVID-19 had greater risk of LVEF <50% versus controls; only hospitalized patients had significantly increased risk of LVEF<40% (aHR, 1.81 [1.35-2.43]) and <30% (aHR, 2.79 [1.72-4.54]). Vaccination was not significantly associated with LVEF decline. Baseline LVEF, older age, male sex, history of heart failure, myocardial infarction, and chronic kidney disease were associated with greater risk. Elevated troponin, B-type natriuretic peptide, D-dimer, and thrombocytopenia predicted greater risk in hospitalized patients with COVID-19.<br><br>CONCLUSIONS: SARS-CoV-2 infection is associated with long-term LVEF declines, especially in hospitalized patients. Vigilant cardiac surveillance may be needed in survivors of COVID-19 to mitigate progressive dysfunction.},
}
@article {pmid41083891,
year = {2026},
author = {Troxel, AB and Krishnan, JA and Verduzco-Gutierrez, M},
title = {The 2024 NASEM Long COVID Definition as a Starting Point for Research.},
journal = {Journal of general internal medicine},
volume = {41},
number = {3},
pages = {856-858},
pmid = {41083891},
issn = {1525-1497},
}
@article {pmid41082082,
year = {2025},
author = {Wasim, R},
title = {From infection to intervention: post-acute sequelae of SARS-CoV-2 infection and cardiovascular risk.},
journal = {Inflammopharmacology},
volume = {33},
number = {11},
pages = {6577-6588},
pmid = {41082082},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/complications ; *Cardiovascular Diseases/etiology/epidemiology/virology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; SARS-CoV-2 ; Biomarkers ; },
abstract = {COVID is now a worldwide epidemic of non-communicable diseases. The symptoms, which impact several organs, might last for hours, weeks, or even months after the SARS-CoV-2 infection has ended. Electrocardiogram abnormalities (ECG), postural orthostatic tachycardia, and supraventricular or ventricular arrhythmias are among the common signs of long COVID-19. According to data, certain patient groups have persistent, post-infectious perimyocarditis, which may lead to left or right ventricular failure, arterial wall inflammation, or microthrombosis. This information has been made available by cardiac and vasculature imaging, and it may be used to develop efficient treatment plans for the cardiovascular symptoms of long COVID. Long COVID requires a greater understanding of the cellular and molecular processes. There are a variety of approaches that have been put forward, some of which include direct impacts on the heart and others that involve microthrombotic damage to the arteries or heart. When evaluated 3 months after SARS-CoV-2 infection, the currently employed circulating biomarkers, such as coagulation and inflammatory markers, do not serve as a highly predictive predictor for the existence or outcome of long COVID. However, further study is required to better understand the underlying processes and particular biomarkers for future COVID preventive methods.},
}
@article {pmid41081723,
year = {2025},
author = {Schlak, A and Seidel, I and Awan, O and Neal, J and Rao, M and Janssen, K and Warner, D and Lee, K and Park, A and Adly, M and Brill, E and Atkins, D and Jones, BE and Wander, PL},
title = {Reaching Consensus on Long COVID Symptoms and Patient-Reported Outcomes Across the Veterans Health Administration Using a Modified Hybrid Nominal Group-Delphi Approach.},
journal = {Medical care},
volume = {63},
number = {11},
pages = {842-850},
doi = {10.1097/MLR.0000000000002194},
pmid = {41081723},
issn = {1537-1948},
mesh = {Humans ; United States ; Delphi Technique ; *COVID-19/complications ; *United States Department of Veterans Affairs ; *Patient Reported Outcome Measures ; *Consensus ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: A consistent approach to track Long COVID symptoms at the Veterans Health Administration (VHA) was lacking.<br><br>OBJECTIVES: To reach consensus among clinical stakeholders on how long COVID symptoms should be assessed at VHA outpatient visits and recommend an assessment battery.<br><br>RESEARCH DESIGN: Hybrid Delphi-Nominal Group approach.<br><br>SUBJECTS: Members of the VHA Long COVID Field Advisory Board (FAB) and the VHA Long COVID Community of Practice (CoP) participated. Veteran stakeholders provided input.<br><br>MEASURES: A literature review and clinician questionnaires identified 68 instruments across 14 symptom domains. In the first consensus round, FAB members excluded instruments with limited clinical usability. The remaining 25 instruments were ranked by CoP members. Multiple rounds of asynchronous voting were conducted until one instrument remained per domain. The top instruments were grouped into 3 batteries. Final consensus on a preferred battery was reached through additional voting. Veterans from the Los Angeles Veteran Engagement Panel assessed clarity, burden, and feasibility.<br><br>RESULTS: The final battery included the Modified Yorkshire COVID-19 Rehabilitation Survey, VHA Whole Health Well-Being Signs, the Exercise Vital Signs Questionnaire, and the 2-Minute Step Test. Whole Health questions were also included to support the VHA's Whole Health System mission. Symptom-specific instruments already used in VHA routine care were not included in the final battery, as clinics already had access to them.<br><br>CONCLUSIONS: A structured, rapid consensus process was used to identify a battery of symptom instruments to standardize Long COVID symptom assessment across VHA clinics.},
}
@article {pmid41080863,
year = {2025},
author = {Heath, GW and Levine, D and Oppong, G and Alghader, M},
title = {Prevalence of post COVID-19 condition and associations with risk factors among U.S. adults: 2023 Behavioral Risk Factor Surveillance System.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1662273},
pmid = {41080863},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Adult ; Behavioral Risk Factor Surveillance System ; Male ; Female ; United States/epidemiology ; Middle Aged ; Risk Factors ; Exercise ; Prevalence ; SARS-CoV-2 ; Aged ; Young Adult ; Adolescent ; },
abstract = {INTRODUCTION: During the COVID-19 pandemic, between 12 and 20% of US adults were identified as having post-COVID-19 condition, commonly referred to as 'Long COVID'. These individuals maintained symptoms of COVID-19 for 3 months or longer following their illness but lacked an active infection. Using the Center for Disease Control's 2023 Behavioral Risk Factor Surveillance System, our hypotheses were that adults who did not meet the 2018 Physical Activity Guidelines for Americans for aerobic and strengthening activities, those not fully vaccinated against COVID-19, and those with certain non-communicable diseases would be at greater odds of reporting post COVID-19 conditions.<br><br>METHODS: The association of post COVID-19 conditions were examined among the 46.4% of adults 18&#x202f;years and older who had tested positive for COVID-19 (n&#x202f;=&#x202f;201,248), with a subset these adults reporting post COVID-19 conditions (n&#x202f;=&#x202f;27,074, 13.6%). Univariate and logistic regression analyses were conducted using SPSS (v29) for complex samples. Univariate analyses were initially conducted on both behavioral risk factors and multiple non-communicable diseases. Subsequently, a series of logistic regression analyses controlling for age, sex, race/ethnicity, and educational attainment were carried out to compare the outcome variable of post-COVID-19 conditions with the exposure variables of (1) not meeting the Physical Activity Guidelines for Americans, (2) not being fully vaccinated, or (3) having the non-communicable diseases of overweight/obesity, coronary heart disease, asthma, or hypertension.<br><br>RESULTS: Adults (n&#x202f;=&#x202f;13,449; 12.2%) who did not meet the Physical Activity Guidelines for Americans were at greater odds of reporting post COVID-19 conditions (aerobic activity - OR&#x202f;=&#x202f;1.19, 95% CI 1.06, 1.33, p&#x202f;<&#x202f;0.0001; strengthening activity - OR&#x202f;=&#x202f;1.02, 95% CI 1.00, 1.03, p&#x202f;<&#x202f;0.001) compared with those meeting the guidelines. Respondents who were not fully vaccinated (&#x2264; 3 vaccinations) were at greater odds of reporting post COVID-19 conditions (OR&#x202f;=&#x202f;1.42, 95% CI, 1.24, 1.49, p&#x202f;<&#x202f;0.0001) compared with those reporting &#x2265;4 vaccinations.<br><br>DISCUSSION: The present findings support the hypothesis that adults who were female, did not achieve the Physical Activity Guidelines, were not fully vaccinated, and had certain non-communicable diseases demonstrated a stronger association with reporting post COVID-19 conditions following COVID-19 infection.},
}
@article {pmid41080807,
year = {2025},
author = {Hammami, N and Karoui, S and Khezami, MA and Ceylan, H&#x130; and Dhahbi, W and Bahlouli, E and Ben Jeddou, I and Dergaa, I and Lebib, S and Ben Salah, FZ and Stefanica, V and Muntean, RI and Dziri, C},
title = {Adapted Physical Activity Protocol Improves Health-Related Quality of Life and Psychological Outcomes in Long COVID: A Prospective Longitudinal Study.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {6445-6457},
pmid = {41080807},
issn = {1178-2390},
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in persistent symptoms in some individuals-referred to as long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). Common symptoms such as fatigue, dyspnea, anxiety, and depression can markedly impair health-related quality of life (HRQOL). Conventional rehabilitation may be insufficient, raising interest in Adapted Physical Activity (APA) as a non-pharmacological strategy to improve physical and psychological outcome. Thus, this study aimed to evaluate the short- and medium-term effects of an APA protocol on HRQOL and psychological outcomes in patients with long COVID.<br><br>METHODS: Fifty non-hospitalized patients with long COVID (mean age 52.0 &#xb1; 15.3 years; 44% female) participated in in a prospective, longitudinal observational study. Each patient underwent a 6-week APA program consisting of two 30-minute individualized cardiorespiratory sessions per week. HRQOL (SF-12), anxiety, and depression (HADS) were evaluated at baseline (E1), immediately post-intervention (E2), and at 5-7 months follow-up (E3).<br><br>RESULTS: Significant improvements were found in both physical and mental SF-12 scores across time points (p&#x202f;<&#x202f;0.001). The proportion of patients with normal physical HRQOL rose from 16% at baseline to 90% at E2 and remained higher than baseline at E3 (66%). Symptoms of anxiety and depression were significantly reduced (p&#x202f;<&#x202f;0.001). Dyspnea prevalence decreased substantially from baseline to follow-ups. Strong negative correlations were observed between HRQOL and HADS scores (p&#x202f;<&#x202f;0.001).<br><br>CONCLUSION: The APA protocol showed significant short- and medium-term improvements in HRQOL and psychological outcomes in long COVID patients. Benefits were more pronounced for physical symptoms and anxiety than for depression. These findings suggest that structured physical activity may offer a feasible, non-pharmacological strategy to enhance recovery and quality of life. Incorporating APA into routine care may help meet the diverse functional and psychological needs of this population.},
}
@article {pmid41080329,
year = {2025},
author = {Martinez Juarez, D and Gomez-Monterrosas, O and Zamora Rosales, F},
title = {Endothelial Dysfunction in a Patient With Post-COVID-19 Syndrome and Mutation of the MTHFR Gene and Prothrombin II.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92056},
pmid = {41080329},
issn = {2168-8184},
abstract = {Post-COVID-19 syndrome (also known as long COVID) is defined as the persistence of cardiovascular symptoms (chest pain, fatigue, palpitations) 12 weeks after the acute phase of SARS-CoV-2 infection. SARS-CoV-2 has been shown to directly infect endothelial cells through ACE2 receptors, leading to endotheliitis and vascular inflammation. In susceptible individuals, this endothelial damage may persist after viral clearance, contributing to coronary microvascular dysfunction. Genetic predispositions (primary thrombophilias) may further aggravate endothelial injury. The prothrombin factor II G20210A mutation has been associated with an increased risk of venous and arterial thrombotic events. The MTHFR gene mutation, particularly the homozygous C677T polymorphism, is associated with reduced activity of methylenetetrahydrofolate reductase, impairing the conversion of homocysteine to methionine. This leads to hyperhomocysteinemia, which contributes to endothelial dysfunction (ED). We report the case of a 25-year-old Mexican woman with a four-month history of chest pain and dyspnea (following a previous COVID-19 infection associated with vaccination). She presented with acute chest pain and dyspnea requiring hospitalization. Echocardiography revealed abnormal regional longitudinal strain in the basal anteroseptal wall (-7%) and basal-mid anterolateral wall (-14% and -16%, respectively), with reduced myocardial work in basal and mid-segments (379-1715 mmHg%). Cardiac magnetic resonance imaging (CMRI) demonstrated myocardial involvement; however, coronary CT angiography (CCTA) excluded obstructive disease. Anti-SARS-CoV-2 IgG levels were markedly elevated (2893 AU/mL). Hematologic evaluation revealed abnormal platelet aggregation with platelet hyperreactivity and the identification of homozygous MTHFR C677T and heterozygous prothrombin factor II G20210A mutations. The patient initially received prophylactic anticoagulation with apixaban during hospitalization, which was discontinued after discharge. Long-term treatment included low-dose aspirin, folic acid, B-complex vitamins, bisoprolol, and trimetazidine for angina control. At a one-year follow-up, the patient showed clinical improvement, with a reduction in the frequency and intensity of angina. This case suggests that patients with platelet hyperreactivity, MTHFR (C677T), and prothrombin factor II (G20210A) mutations may be predisposed to developing ED and coronary microcirculatory impairment following SARS-CoV-2 infection in post-COVID-19 syndrome. We address the use of prophylactic anticoagulants in selected cases such as ours, which, although not specifically recommended by current guidelines (American Society of Hematology), may be considered after an individualized risk-benefit assessment.},
}
@article {pmid41079753,
year = {2025},
author = {Dadsena, R and Wetz, S and Hofmann, A and Costa, AS and Romanzetti, S and Lischewski, SA and Krockauer, C and Balloff, C and Binkofski, F and Schulz, JB and Reetz, K and Walders, J},
title = {Evidence of clinical and brain recovery in post-COVID-19 condition: a three-year follow-up study.},
journal = {Brain communications},
volume = {7},
number = {5},
pages = {fcaf366},
pmid = {41079753},
issn = {2632-1297},
abstract = {Fatigue and cognitive dysfunction linked to persistent brain changes have been reported for up to two years after COVID-19. In this study, we followed the clinical, neuroimaging and fluid biomarker trajectories over three years post SARS-CoV-2 infection to evaluate potential signs and underlying factors of brain recovery. We conducted a monocentric, longitudinal study using resting-state functional and structural T1-weighted magnetic resonance imaging data from 51 patients with post-COVID-19 condition (mean age 50 years, 33 female) collected at a mean time of 6, 23 and 38 months after COVID-19 infection. The trajectory of brain changes was compared to 23 age- and sex-matched healthy controls (mean age 37 years, 13 female) with similar time intervals between brain scans and analysed in relation to clinical, neuropsychological and fluid biomarkers including interleukins and neurodestruction markers at all timepoints. In addition, hand grip strength to evaluate muscular fatigue was assessed at the final follow-up visit. Self-reported fatigue improved over time but was still moderate on average three years after COVID-19 infection, while measures of hand grip strength and cognitive performance were largely unaffected. We found a significant increase of both lateral ventricles (∼8%) and the third (∼6%) ventricle accompanied by a structural volume reduction in adjacent areas including the thalamus, pallidum, caudate nucleus and putamen. An increased neuronal activation pattern was widespread and pronounced in these areas. The brainstem no longer exhibited volume loss as reported in our pervious study, but enhanced functional connectivity. Laboratory markers including interleukins and neuronal injury markers remained within the normal reference ranges across all study timepoints. Our study revealed an overall slow but evident clinical improvement, including improved fatigue, regular muscular strength and recovery as well as normal cognitive function without signs of systemic inflammation three years after COVID-19. Clinical improvement is reflected by a pattern of brain recovery along periventricular regions. This pattern is characterized by structural stabilization and increased connectivity starting in the brainstem as well as efficient neuronal recruitment and increased activation in the basal ganglia, with no evidence of neuronal injury. These results highlight the positive long-term recovery trajectory in post-COVID patients.},
}
@article {pmid41079027,
year = {2025},
author = {Damant, RW and Rourke, L and Lam, GY and Smith, MP and Weatherald, J and Laratta, CR and Fuhr, DP and Cui, Y and Stickland, MK and Ferrara, G},
title = {Exploring the temporal relationship between stigma, disease manifestations, and health outcomes in post COVID-19 condition: a longitudinal descriptive study.},
journal = {EClinicalMedicine},
volume = {89},
number = {},
pages = {103531},
pmid = {41079027},
issn = {2589-5370},
abstract = {BACKGROUND: Stigma is defined as a deeply discrediting attribute. Post COVID-19 Condition (PCC) is now recognized to be a source of health-related stigma and discrimination capable of negatively impacting the well-being of those affected. Our purpose was to explore the relationship between PCC-related stigma, disease manifestations, and health outcomes over time.<br><br>METHODS: Using previously validated instruments to measure PCC-related stigma, symptoms, depression, quality of life, function, and occupational status, we conducted a longitudinal descriptive study in a cohort of individuals with confirmed PCC between May 12 and August 13, 2023 in the Canadian city of Edmonton.<br><br>FINDINGS: Ninety-nine consenting participants completed study questionnaires 3-24 months following an initial diagnosis of PCC (enrollment) and again a mean (SD) of 1.6 (0.26) years later (follow-up). Individuals experienced marked variability in study scores over time. Measures of central tendency proved inadequate to detect changes within the cohort. There was minimal attenuation of stigma scores between enrollment and follow-up despite a "return to normal" from earlier pandemic responses: the change in mean stigma score from enrollment to follow-up was -0.2 (p = 0.97). Significant correlations were found between enrollment stigma and symptoms, depression, function, and quality of life measured at follow-up (r = 0.45-0.55). Similar correlations were noted between enrollment stigma and follow-up composite disease manifestation, health outcome, and global well-being scores (r = 0.39-0.54). Multivariate multiple regression demonstrated statistically significant associations between the change in stigma from enrollment to follow-up and symptoms, depression, functional status, and quality of life (B = -0.45 to -0.11). When participants were categorized as "improved stigma at enrollment" vs. "unchanged or worse stigma at enrollment", changes in stigma over time appeared to be predictive of disease manifestations and health outcomes at follow-up (Cohen's d = 0.43-0.77).<br><br>INTERPRETATION: This study provides insights into the temporal relationship between PCC-related stigma, disease manifestations, and health outcomes and could establish a foundation for screening, prognostication, treatment, and other efforts to mitigate the impact of stigma.<br><br>FUNDING: The Long COVID Web is funded by the Canadian Institute of Health Research (CIHR)-Grant #185352.},
}
@article {pmid41076807,
year = {2025},
author = {Domingo, JL},
title = {Differentiating COVID-19 vaccine-related adverse events from long COVID: A comprehensive review of clinical manifestations, pathophysiology, and diagnostic approaches.},
journal = {Vaccine},
volume = {66},
number = {},
pages = {127842},
doi = {10.1016/j.vaccine.2025.127842},
pmid = {41076807},
issn = {1873-2518},
mesh = {Humans ; *COVID-19 Vaccines/adverse effects/administration &amp; dosage ; *COVID-19/prevention &amp; control/diagnosis/immunology ; SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Vaccination/adverse effects ; },
abstract = {The global deployment of COVID-19 vaccines has introduced diagnostic challenges due to overlapping symptoms with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), prompting a comprehensive review of vaccine safety profiles, long COVID manifestations, and evidence-based differentiation strategies. Through a literature search (PubMed, Scopus, Web of Science) from December 2020 to June 2025, including peer-reviewed studies, clinical trials, and cohort studies, the present review reports that COVID-19 vaccines maintain robust safety, with rare adverse events like myocarditis and thrombosis with thrombocytopenia syndrome, while long COVID affects 10-40 % of SARS-CoV-2 survivors, presenting symptoms such as fatigue, cognitive dysfunction, and dyspnea. Differentiation between these conditions relies on careful analysis of the timing of symptom onset, detailed symptom characterization, and the use of advanced diagnostic tools. Systematic clinical assessment is essential for accurate diagnosis, which is critical for appropriate patient management, maintaining public confidence in vaccination, and guiding future research. Further studies are needed to validate diagnostic biomarkers, develop targeted therapies, and monitor long-term outcomes, with standardized global registries and interdisciplinary collaboration identified as key priorities for improving care and advancing the field.},
}
@article {pmid41075953,
year = {2026},
author = {Salmam, I and Tittley, J and Drouin, G and Perreault, K and Desmeules, F and Paquette, JS and Roy, JS and Best, KL},
title = {Metabolic and ventilatory constraints in long COVID individuals.},
journal = {Respiratory physiology &amp; neurobiology},
volume = {339},
number = {},
pages = {104504},
doi = {10.1016/j.resp.2025.104504},
pmid = {41075953},
issn = {1878-1519},
mesh = {Humans ; *COVID-19/physiopathology/metabolism/complications ; Male ; Female ; *Oxygen Consumption/physiology ; Middle Aged ; Cross-Sectional Studies ; *Exercise Tolerance/physiology ; Adult ; Longitudinal Studies ; *Pulmonary Ventilation/physiology ; Post-Acute COVID-19 Syndrome ; Walk Test ; Aged ; Exercise Test ; *Cardiorespiratory Fitness/physiology ; },
abstract = {Long COVID is characterized by persistent symptoms and physiological impairments beyond acute infection. Oxygen consumption (VO2) and ventilatory efficiency, key indicators of cardiorespiratory fitness, are commonly diminished in this population, contributing to exercise intolerance. This study compared cardiorespiratory patterns and exercise capacity among individuals with Long COVID (LCG), those with resolved symptoms (Short COVID; SCG), and healthy controls (CG). The secondary objective was to assess longitudinal changes over six months. Cross-sectional comparisons at baseline addressed the primary objective, while the longitudinal component explored on changes over time. Participants included 94 in the LCG, 100 in the SCG, and 70 in the CG. All performed a 6-minute walk test (6MWT) during which peak oxygen uptake (VO2peak), minute ventilation (VE), and VE/VCO2 (ratio of VE to carbon dioxide output, reflecting ventilatory efficiency) were continuously measured using the Metamax 3B system. Baseline differences were assessed by one-way ANOVA, and longitudinal changes by generalized estimating equations. At baseline, VO2peak was significantly reduced in the LCG (70.1 % predicted) versus SCG (80.6 %) and CG (84.6 %) (p = 0.001). VE/VCO2 was elevated in the LCG (30.2 ± 4.2) compared to SCG (27.9 ± 2.8) and CG (28.7 ± 3.3) (p < .001). The 6MWT distance was also lower in the LCG (484 ± 127 m) than SCG (607 ± 69.1 m) and CG (571 ± 89.6 m) (p < .001). No statistically significant Group × Time interaction emerged between the groups. Individuals with Long COVID exhibited persistent ventilatory inefficiency and reduced exercise capacity, with impairments persisting over six months, underscoring the need for targeted rehabilitation. SHORT ABSTRACT: Individuals with Long COVID exhibit reduced exercise capacity and persistent ventilatory inefficiency compared to Short COVID and control groups. At baseline and over six months, VO2, VE/VCO2, and 6MWT distances were significantly impaired, highlighting the need for targeted rehabilitation strategies to address ongoing physiological limitations in this population.},
}
@article {pmid41074231,
year = {2025},
author = {Reagu, S and Alabdulla, M and Kader, NKA and Ajmal, NA and Abdelgafar, SKH and Wadoo, O},
title = {Long-term symptoms after SARS-CoV-2 infection in a cohort of healthcare workers in Qatar.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1282},
pmid = {41074231},
issn = {1471-2334},
abstract = {BACKGROUND: During the Coronavirus Disease 2019 pandemic, healthcare workers faced a significantly elevated risk of exposure and infection compared to the general population due to their frontline roles in patient care. This heightened risk was compounded by the nature of their work environment and prolonged contact with infected individuals. Despite extensive research on the virus’s immediate impact, limited data exists regarding the prevalence of long-term symptoms, commonly referred to as Long COVID, among healthcare workers. In this study, we aimed to investigate the prevalence and profile of long-term symptoms following SARS-CoV-2 infection, along with associated risk factors, among healthcare workers, with a particular focus on regional data from the Middle East, and to contextualize these findings within the global evidence base.<br><br>METHODS: This cross-sectional, web-based survey was conducted among healthcare workers at Hamad Medical Corporation, the largest healthcare provider in Qatar, between 24 January 2022 and 24 April 2022. Healthcare workers aged 18 years or older, including physicians, nurses, allied healthcare professionals, and administrative staff, were eligible to participate. The survey assessed the prevalence of Long COVID-19 symptoms, and the symptoms of depression, and anxiety. Over a four-week data collection period, we received 783 complete responses, which exceeded the minimum required sample size.<br><br>RESULTS: Of the respondents, three-quarters reported long-term symptoms after SARS-CoV-2 infection, and one-third reported more than three symptoms. Fatigue was the most common symptom. Gender disparities were observed, with females experiencing a higher incidence of symptoms. Significant associations were identified between a history of SARS-CoV-2 infection, a psychiatric history, symptoms of depression, and the development of multiple Long COVID-19 symptoms.<br><br>CONCLUSION: These findings highlight the significant burden of Long COVID-19 symptoms on healthcare workers well-being in Qatar. The study underscores the need for targeted interventions to support them, especially those at greater risk of adverse outcomes. From a healthcare system perspective, addressing Long COVID-19 symptoms among healthcare workers is critical to maintaining a resilient workforce. This includes implementing access to mental health resources, structured follow-up, and workplace accommodation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-11372-w.},
}
@article {pmid41074076,
year = {2025},
author = {Farré, X and Blay, N and Iraola-Guzmán, S and Fernández-Jiménez, F and Alzate-Piñol, S and Llucià-Carol, L and Espinosa, A and Castaño-Vinyals, G and Dobaño, C and Moncunill, G and Karachaliou, M and Garcia-Aymerich, J and Kogevinas, M and Barceló, C and Cadenas, I and de Cid, R},
title = {VEGFA sex-specific signature is associated to long COVID symptom persistence.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {552},
pmid = {41074076},
issn = {1741-7015},
support = {TED2021-130626B-I00//Ministerio de Ciencia e Innovaci&#xf3;n/ ; CEX2018-000806-S//Ministerio de Ciencia e Innovaci&#xf3;n/ ; 167/C/2021//Fundaci&#xf3; la Marat&#xf3; de TV3/ ; SR20-01024//'la Caixa' Foundation/ ; PI20/01267//Ministerio de Sanidad, Pol&#xed;tica Social e Igualdad/ ; PI18/01512//Ministerio de Sanidad, Pol&#xed;tica Social e Igualdad/ ; GA:101046314//HORIZON EUROPE Framework Programme/ ; },
mesh = {Humans ; Female ; *COVID-19/blood/metabolism ; Male ; *Vascular Endothelial Growth Factor A/blood/metabolism ; Middle Aged ; Sex Factors ; Aged ; SARS-CoV-2 ; Biomarkers/blood ; Adult ; Proteomics ; },
abstract = {BACKGROUND: Long COVID involves persistent symptoms after COVID-19 recovery, affecting multiple organ systems for months or years. Risk factors include female sex, prior chronic conditions, severe SARS-CoV-2 infection, reinfections, and lack of vaccination. As a major public health concern, ongoing research continues to investigate its causes, mechanisms, and long-term effects.<br><br>METHODS: Proteomic expression analysis of 171 individuals, in two time points, with confirmed SARS-CoV-2 infection, including 133 long COVID patients from the deeply characterized COVICAT cohort, assessed 1395 protein biomarkers using Olink&#xae; technology. Statistical analyses with linear mixed models examined protein expression changes, long COVID status, and sex-specific differences. Functional analysis included gene set enrichment analysis and protein-protein interaction networks.<br><br>RESULTS: Findings revealed VEGFA overexpression in long COVID patients (effect size 0.322, SE&#x2009;=&#x2009;0.098, p&#x2009;=&#x2009;0.0013), along with sex-specific expression patterns and the influence of sex-hormonal status in females, with significant overexpression of circulating VEGFA levels specifically in postmenopausal women (Mann-Whitney U test p value&#x2009;=&#x2009;8.55&#x2009;&#xd7;&#x2009;10[-3]). Network analysis identified 109 nodes and 274 edges, with VEGFA ranking highest in centrality. Dysregulated chemokine signaling, complement activation, and viral reactivation were also confirmed, consistent with prior studies.<br><br>CONCLUSIONS: Using high-throughput proteomic profiling in a population-based cohort, we observed that vascular dysfunction, particularly involving VEGFA, is a key feature of long COVID, especially in milder cases, with significant overexpression of VEGFA in postmenopausal women. Sex-specific proteomic patterns suggest distinct recovery mechanisms, highlighting the need to consider sex, vascular health, and disease severity in the pathogenesis and management of long COVID.},
}
@article {pmid41073932,
year = {2025},
author = {Yan, X and Zhao, X and Wang, H and Du, Y and Liu, L and Liu, J and Wang, Q and Wei, S},
title = {Impact of vaccination on SARS-CoV-2 infections and long COVID symptoms: a cross-sectional study in China.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1266},
pmid = {41073932},
issn = {1471-2334},
support = {72061137006//National Natural Science Foundation of China/ ; 2022YFC2305103//National Key Research and Development Program of China/ ; },
abstract = {BACKGROUND: Following the adjustment of the dynamic zero-COVID-19 strategy, China has witnessed a rapid increase in COVID-19 cases. However, the relationship between diverse vaccination statuses and the spectrum of symptom presentation, disease severity, and long-term post-COVID conditions remains to be fully understood. This study aimed to assess the impact of vaccination on the incidence of SARS-CoV-2 infections, the manifestation of acute symptoms, and the occurrence of long-term symptoms post-infection within the context of China's revised pandemic prevention and control measures.<br><br>METHODS: This study investigated 6,572 participants from the Yichang COVID-19 Antibody Longitudinal Survey (YC-CALS) in March 2023, focusing on demographic and health-related information, including vaccination history, infection status, and symptomatology. Univariate and multivariate analysis methods were used to determine the correlations between vaccination status and COVID-19 outcomes.<br><br>RESULTS: Among the surveyed participants, 85.91% reported positive for SARS-CoV-2. Of those who were positive, 96.79% experienced at least one common symptom, with fever (79.34%), cough (62.56%), and fatigue (60.59%) being the most reported symptoms. Despite the high incidence of symptoms, only 2.05% of those who tested positive needed hospitalization. Importantly, symptoms such as palpitations, chest pain, and shortness of breath persisted beyond 90&#xa0;days in certain individuals. Booster shots significantly reduced the risk of specific symptoms including dyspnea, eye soreness and fatigue, and gastrointestinal discomfort (P&#x2009;<&#x2009;0.05). Vaccination beyond 12&#xa0;months significantly increased symptoms such as decreased sense of smell, palpitations, and chest distress (P&#x2009;<&#x2009;0.05). Additionally, the study found a positive correlation between the timing of vaccination and the development of long COVID symptoms, with individuals vaccinated more than 12&#xa0;months prior exhibiting a higher likelihood of enduring symptoms such as fatigue (OR&#x2009;=&#x2009;1.218, P&#x2009;=&#x2009;0.023) and headache dizziness (OR&#x2009;=&#x2009;1.244, P&#x2009;=&#x2009;0.038) for over one month.<br><br>CONCLUSIONS: The findings highlight the critical importance of vaccination in controlling the spread of COVID-19 and reducing symptoms and disease prognosis, providing important insights for future vaccine policy.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-11677-w.},
}
@article {pmid41073921,
year = {2025},
author = {Takamatsu, N and Kuga, H},
title = {Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1275},
pmid = {41073921},
issn = {1471-2334},
support = {JP23K02953//Japan Society for the Promotion of Science/ ; },
abstract = {BACKGROUND: Long COVID presents a spectrum of persistent symptoms that substantially overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including debilitating fatigue, post-exertional malaise, cognitive dysfunction, and neuropsychiatric manifestations. Despite growing evidence of shared pathophysiological mechanisms, neither condition has established diagnostic biomarkers or disease-modifying treatments. Cognitive behavior therapy (CBT), when appropriately implemented, may serve as one component of comprehensive care. This review examines the neuropsychiatric manifestations, management principles, and implementation considerations for CBT in long COVID, drawing insights from ME/CFS experience.<br><br>MAIN BODY: Our analyses revealed substantial overlap between patients with long COVID and ME/CFS including immune dysregulation, neuroinflammation, and metabolic dysfunction while identifying distinct features in disease trajectories. Evidence suggests ME/CFS may represent a severe phenotype in a subset of patients with long COVID. Management principles applicable to both conditions include patient validation, comprehensive needs assessment, individualized energy management, symptom-specific interventions, and comorbidity management. Current clinical trials demonstrate methodological evolution in CBT implementation, from traditional protocols to digital platforms. Moderate-certainty evidence indicates CBT may reduce fatigue and improve cognitive function in long COVID. However, substantial heterogeneity exists in both intervention characteristics and condition definitions. Implementation success requires provider competency, terminological precision, and individualized approaches that respect energy limitations. Careful monitoring for post-exertional symptom exacerbation is essential. We emphasize that these approaches do not imply these conditions are primarily psychological.<br><br>CONCLUSION: Our review synthesizes current evidence on CBT in long COVID management, considering lessons from ME/CFS. Substantial challenges remain in standardizing terminology, strengthening trial methodology, and determining optimal implementation strategies. Future research should incorporate objective outcome measures alongside subjective reports, while clinical practice should consider how cognitive-behavioral approaches might contribute to comprehensive care plans tailored to individual patient needs. This approach recognizes that addressing both physical and psychological dimensions of these conditions may enhance treatment outcomes, while acknowledging the individualized nature of patient responses to different therapeutic elements.},
}
@article {pmid41073392,
year = {2025},
author = {Baik, M and Yeom, J and Lee, SM and Jeong, H and Lee, AR and Seo, S and Choi, SM and Jo, Y and Park, HY and Kim, EY and Paik, JW},
title = {Discovery of molecular signature of long-term psychiatric sequelae in COVID-19 through proteome profiling of dried blood spots.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {389},
pmid = {41073392},
issn = {2158-3188},
mesh = {Humans ; *COVID-19/complications/psychology/blood ; Male ; Female ; Middle Aged ; Adult ; Dried Blood Spot Testing ; Proteomics/methods ; *Proteome ; *Mental Disorders/blood/etiology ; Aged ; SARS-CoV-2 ; Biomarkers/blood ; },
abstract = {Neuropsychiatric sequelae represent a significant aspect of post-acute sequelae of SARS-CoV-2 (PASC, or long COVID), posing considerable public health challenges. This study identified molecular signatures associated with PASC in individuals with psychiatric morbidities via dried blood spot proteomic analysis. We evaluated 51 COVID-19 survivors ≥ 60 days post-infection, categorizing them into three groups: those with new-onset psychiatric disorders (n = 16, psychiatric PASC), those with persistent symptoms but no psychiatric disorders (n = 18, general PASC), and those symptomatically recovered (n = 17, recovered). Liquid chromatography-mass spectrometry analysis identified 1604 proteins. Differentially expressed proteins underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Protein panels, including isoform 1 of fibronectin, sorbitol dehydrogenase, cytosolic acyl coenzyme A thioester hydrolase, and apolipoprotein A-II, differentiated psychiatric PASC from recovered individuals with an area under the curve (AUC) of 0.865 (95% CI: 0.658-1). Filamin A and vacuolar protein sorting-associated protein VTA1 homolog distinguished psychiatric PASC from general PASC at an AUC of 0.831 (95% CI: 0.6-1). Decision tree analysis revealed that alpha-synuclein, pyruvate kinase PKM, and sorbitol dehydrogenase effectively distinguished the three groups with 82% classification accuracy. These findings suggest that alterations in immune, glucose, and lipid metabolism pathways, along with neuroinflammation and neurodegeneration, contribute to the psychiatric PASC phenotype and highlight potential biomarkers for psychiatric disorders during the long-term COVID-19 clinical course.},
}
@article {pmid41073313,
year = {2025},
author = {Wang, MC and Liu, X and Hu, K},
title = {[Intermittent hypoxia exposure in the rehabilitation of long COVID patients].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {10},
pages = {961-964},
doi = {10.3760/cma.j.cn112147-20250601-00295},
pmid = {41073313},
issn = {1001-0939},
support = {JCRCYG-2022-012//Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University/ ; },
mesh = {Humans ; *COVID-19/rehabilitation ; *Hypoxia/rehabilitation ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; },
abstract = {Patients recovering from COVID-19 infection often experience "Long COVID", which is characterized by symptoms such as fatigue, reduced exercise capacity or dyspnea, and cognitive dysfunction. These symptoms negatively impact their quality of life. Currently, there is a lack of widely recognized therapeutic approaches or specific pharmacological interventions for managing these conditions. During intermittent hypoxic exposure (IHE), participants are alternated to hypoxic and normoxic exposure, which induced beneficial adaptive responses in the body. Emerging evidence suggests that IHE can alleviate symptoms of Long COVID through mechanisms such as improving ventilatory function, enhancing cardiopulmonary endurance, modulating immune responses, and reducing inflammation. These effects contribute to an improved quality of life and more holistic recovery, highlighting the promising potential of IHE in managing long COVID.},
}
@article {pmid41072669,
year = {2026},
author = {Baalbaki, N and van Egmond, D and Jaeger, P and Cornelissen, MEB and Verbeek, ST and Sokolowska, M and van Drunen, CM and Maitland-van der Zee, AH and Golebski, K and , },
title = {Barrier dysfunction in nasal epithelium contributes to persistent inflammation in long COVID.},
journal = {The Journal of allergy and clinical immunology},
volume = {157},
number = {1},
pages = {203-216},
doi = {10.1016/j.jaci.2025.09.024},
pmid = {41072669},
issn = {1097-6825},
mesh = {Humans ; *COVID-19/immunology/pathology ; *Nasal Mucosa/immunology/pathology/metabolism ; *SARS-CoV-2/immunology ; Male ; Female ; *Inflammation/immunology/pathology ; Middle Aged ; Cytokines/metabolism/immunology ; Adult ; Aged ; Lymphocytes/immunology ; },
abstract = {BACKGROUND: Long COVID (LC) is characterized by persistent symptoms associated with chronic inflammation and immune dysregulation, but the local tissue mechanisms driving these processes remain poorly understood.<br><br>OBJECTIVE: Given that the nasal epithelium is the primary entry and infection site for SARS-CoV-2, we aimed to investigate its role in LC and its potential contribution to systemic immune activation.<br><br>METHODS: We analyzed nasal epithelial samples and peripheral blood from participants in the Precision Medicine for More Oxygen (P4O2) COVID-19 cohort, post-COVID-19 individuals, and healthy controls. We assessed epithelial barrier integrity, evaluated wound healing, and explored cytokine profiles. Transcriptomic analysis was performed via RNA sequencing. Blood innate lymphoid cells (ILCs) were phenotyped by flow cytometry and stimulated in vitro for functional assays.<br><br>RESULTS: Among a subgroup of LC patients, nasal epithelial cells showed impaired barrier function, reduced expression of ZO-1 and occludin and exaggerated sensitivity to viral triggers. Despite faster wound closure, the epithelial repair was reduced. The LC nasal epithelium exhibited increased cytokine production, including IL-1&#x3b2; and transcriptomic signatures of inflammation, including upregulation of interferon pathways. Furthermore, we found that TFs ATF3 and EGR1 were downregulated in LC. Elevated IL-1&#x3b2; levels in nasal epithelium promoted ILC activation and plasticity toward IFN-&#x3b3;-producing ILCs in blood.<br><br>CONCLUSION: While multiple organ systems are implicated in LC, our findings identified nasal epithelial dysfunction in a subgroup of LC patients and chronic activation as potential contributors to systemic immune dysregulation. The IL-1&#x3b2;-IFN-&#x3b3; axis represents a novel targetable pathway that may support precision therapies for LC.},
}
@article {pmid41072215,
year = {2025},
author = {Wang, Q and Gao, F and Zhu, D and Ren, H and Xu, Y and Lou, M and Fei, C and Xu, X and Yu, Z and Ren, Z},
title = {Alterations in the oral microbiome detected during long-term follow-up of COVID-19 recovered patients.},
journal = {Journal of infection and public health},
volume = {18},
number = {12},
pages = {102983},
doi = {10.1016/j.jiph.2025.102983},
pmid = {41072215},
issn = {1876-035X},
mesh = {Humans ; *COVID-19/microbiology/rehabilitation ; Male ; Female ; Middle Aged ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Follow-Up Studies ; Adult ; *Tongue/microbiology ; *Mouth/microbiology ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: The oral biome was significantly altered in COVID-19 patients, but there is still a gap in long-term follow-up studies of the oral microbiota of recovering patients.<br><br>METHODS: We recruited 62 patients with a confirmed COVID-19 diagnosis and collected tongue moss samples at three time points: 1 month (RP1), 3 months (RP3) and 5 months (RP5) of rehabilitation. We then sequenced the tongue samples for 16S rRNA amplicons.<br><br>RESULTS: The results showed that there was no significant difference in the oral microbial composition of patients who had been rehabilitated for 3 months compared to those who had been rehabilitated for 1 month, whereas patients who had been rehabilitated for 5 months showed a significant increase in the diversity of the oral microbiome compared to those who had been rehabilitated for 1 month. In addition, we characterized the dynamics of the oral microbiome of COVID-19 patients during their rehabilitation.<br><br>CONCLUSION: As patients recover, the diversity of their oral microbiome gradually returns to normal, providing microbiological evidence for the clinical diagnosis and treatment strategies of COVID-19.},
}
@article {pmid41071398,
year = {2025},
author = {Palladini, M and Azzalin, AA and Bessi, M and De Lorenzo, R and Rovere-Querini, P and Benedetti, F and Mazza, MG},
title = {Cytokine Blockade Attenuates Inflammation and Improves Depressive Psychopathology After COVID-19: A Naturalistic Observational Study.},
journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology},
volume = {20},
number = {1},
pages = {86},
pmid = {41071398},
issn = {1557-1904},
support = {GR-2021-12374872-1//Italian Ministry of Health/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/psychology/immunology/complications ; *Inflammation/drug therapy/immunology/psychology ; *Cytokines/antagonists &amp; inhibitors ; Adult ; *Depression/drug therapy/etiology/immunology ; Aged ; *COVID-19 Drug Treatment ; *Antidepressive Agents/therapeutic use ; },
abstract = {Current insight on inflammation in psychiatry suggests that perturbation of inflammatory set points could foster psychopathology and recent evidence support immune-inflammatory mechanisms as targets for antidepressant pharmacology. In the present naturalistic observational study we evaluated the possible effect of the cytokine-blocking agents in preventing the development of post-COVID depression in a large sample of survivors also exploring the relationship between post-COVID depressive risk, treatment with cytokine-blocking agents, and innate immune response markers. 588 COVID-19 survivors were included, of them 374 received the best available treatment at the time and 131 received standard treatment combined with cytokine-blocking agents (anakinra, tocilizumab, sarilumab, reparixin and mavrilimumab). Post-COVID depressive psychopathology was evaluated at short (34.6 ± 17.39 days) and long term (126.76 ± 61.4 days) follow-ups. The systemic inflammation index as (neutrophils*platelets)/lymphocytes was computed in a subgroup of 274 patients. COVID-19 survivors who were treated with cytokine-blocking agents experienced less severe depressive symptomatology and, simultaneously, less susceptibility to develop clinically relevant depression. Moreover, the longitudinal investigations, revealed that patients treated with cytokine-blocking agents underwent a spontaneous symptoms relief over time. Systemic inflammation index decrease over hospitalization was found to affect the susceptibility to long-term depression. Finally, we observed that cytokine-blocking agents' impact on depression was mediated by lowering of systemic inflammation. Our findings indicate potential efficacy of cytokine-blocking agent treatment during the early stages of COVID-19, mitigating post-COVID depressive symptoms by attenuating systemic inflammation. Further investigation through preclinical and clinical studies is warranted to elucidate immune-inflammatory pathways as viable targets for antidepressant psychopharmacology.},
}
@article {pmid41070112,
year = {2025},
author = {Nuber-Champier, A and Breville, G and Voruz, P and Jacot de Alcântara, I and Lalive, PH and Allali, G and Benzakour, L and Lövblad, KO and Braillard, O and Nehme, M and Coen, M and Serratrice, J and Reny, JL and Pugin, J and Guessous, I and Landis, BN and Cionca, A and Assal, F and Péron, JA},
title = {Inflammatory predictors of Post-COVID fatigue.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {49},
number = {},
pages = {101109},
pmid = {41070112},
issn = {2666-3546},
abstract = {The biological mechanisms underlying objective and subjective fatigue in post-COVID syndrome remain unclear. This study investigates whether immune responses during the acute phase of SARS-CoV-2 infection predict fatigue dimensions 6-9 months post-infection. We analyzed serum immune markers from 54 hospitalized patients (mean age: 58.69 ± 10.90 yrs; female: 31 %) and assessed their association with chronic fatigue using general linear mixed models. Elevated levels of IL-1RA, IFNγ, TNFα, and monocyte percentage during acute infection predicted increased physical and total fatigue. Additionally, higher TNFα levels (r = -0.40, p = .019) correlated with reduced awareness of cognitive fatigue. These findings highlight the role of acute inflammation in the persistence of post-COVID fatigue.},
}
@article {pmid41070108,
year = {2025},
author = {Rwamwejo, F and Niyonkuru, VU and Rukundo, G and Remera, E and Rwagasore, E and Sztandera, L and Ruranga, C and Krebs, E},
title = {Prevalence and characterization of post-acute sequelae of SARS-CoV-2 infection (PASC) in Rwanda.},
journal = {IJID regions},
volume = {17},
number = {},
pages = {100738},
pmid = {41070108},
issn = {2772-7076},
abstract = {OBJECTIVES: Reliable, population-level estimates of post-acute sequelae of SARS-CoV-2 infection (PASC) remain scarce for sub-Saharan Africa. We aimed to quantify PASC prevalence and identify associated factors among adult COVID-19 survivors in Rwanda.<br><br>METHODS: A nationally representative cross-sectional telephone survey (August-October 2024) sampled 3143 adults from the national COVID-19 registry. PASC was defined as new or persisting symptoms &#x2265;3 months after acute illness and lasting &#x2265;2 months. The prevalence was calculated, and multivariable logistic regression identified factors independently associated with PASC.<br><br>RESULTS: Overall, PASC prevalence was 34%. Leading symptoms were back pain, headache, dizziness, fatigue, and reduced sexual desire. Higher odds of PASC occurred in women, adults &#x2265;35 years, individuals with &#x2265;2 COVID-19 infections, and those screening positive for anxiety. Current alcohol use was linked to lower odds. COVID-19 vaccination showed no association with PASC.<br><br>CONCLUSIONS: Approximately one-third of adult Rwandan COVID-19 survivors continue to experience persistent symptoms. This burden signals that post-COVID care must become an integral part of routine health services, especially as new variants periodically drive fresh waves of infection. Preventing repeat infections and integrating mental health support emerge as actionable priorities. Harmonized longitudinal studies are needed to clarify PASC causality.},
}
@article {pmid41069316,
year = {2025},
author = {Agergaard, J and Frostholm, L and Fink, P and Dantoft, TM and Schiøttz-Christensen, B and Petersen, MW},
title = {Symptom profiles in long COVID compared to functional somatic disorder and the general population.},
journal = {Danish medical journal},
volume = {72},
number = {10},
pages = {},
doi = {10.61409/A09240627},
pmid = {41069316},
issn = {2245-1919},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Male ; Female ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Adult ; *Somatoform Disorders/epidemiology/diagnosis/physiopathology ; Prevalence ; Aged ; SARS-CoV-2 ; Fatigue/epidemiology ; Surveys and Questionnaires ; Denmark/epidemiology ; },
abstract = {INTRODUCTION: Long COVID, characterised by persistent symptoms following COVID-19, affects about 10% of individuals recovering from SARS-CoV-2. The overlap of symptoms described in long COVID and functional somatic disorder (FSD) raises questions about shared pathophysiology. This report compares the prevalence and profiles of physical symptoms among patients with long COVID, patients with FSD and the general population.<br><br>METHODS: Data from a cohort of patients with long COVID referred for diagnostics, a cohort of patients seen in a regional clinic for FSD and individuals from the general population were used. Questionnaires, including the bodily distress syndrome checklist, were used to assess physical symptoms.<br><br>RESULTS: A total of 436 patients with long COVID, 264 patients with FSD and 9,656 individuals from the general population were included. A lower prevalence of symptoms was observed in patients with long COVID than in patients with FSD. However, the prevalence of symptoms in patients with long COVID remained higher than in the general population. In patients with long COVID, dominant symptoms were from the general symptoms (GS) cluster (concentration difficulties, fatigue, headache, memory problems) and muscle pain. Additionally, 11% met the criteria for multi-organ FSD, exhibiting a similar symptom profile to patients with FSD.<br><br>CONCLUSIONS: A total of 11% of long COVID patients had a symptom profile similar to that of patients with multi-organ FSD. GS, including fatigue and muscle pain, were common. These findings highlight the need for prospective studies to identify patients with similar symptoms, pathogenesis and treatment options.<br><br>FUNDING: None.<br><br>TRIAL REGISTRATION: Not relevant.},
}
@article {pmid41068758,
year = {2025},
author = {Rochette, C and Pontevia, AFA and Francois, J},
title = {Individuals' perceptions of Long Covid: a phenomenological approach to an online health community narratives.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {1336},
pmid = {41068758},
issn = {1472-6963},
abstract = {BACKGROUND: In 2023, it was estimated that at least 65 million individuals had Long Covid (LC). Yet the literature reveals a lack of knowledge on how individuals perceive and experience LC symptoms. This study aims to explore how individuals with Long Covid describe their symptoms across physical, cognitive, emotional, social, and behavioural dimensions, and to analyse these experiences through the lens of the Symptom Management Theory (SMT) using a phenomenological and netnographic approach to spontaneous patient narratives.<br><br>METHODS: A netnographic study was conducted on 63 selected participants in France from 19 April 2020 to 31 December 2022. Narratives were first analysed phenomenologically using TROPES software. Verbatims were then coded through content analysis with NVivo12Pro and organised according to the SMT dimensions of symptom experience.<br><br>RESULTS: The study revealed that the testimonies of Long Covid patients are characterized by an argumentative, personal, and chronological discourse, highlighting the intensity of persistent symptoms and their significant impact on daily life. The most frequent symptoms identified include bodily pain, respiratory issues, chronic fatigue, as well as sensory and cognitive disturbances, along with significant emotional and social challenges.<br><br>CONCLUSIONS: Our study demonstrates the profound and multidimensional impact of Long Covid on patients&#x2019; daily lives, highlighting the need for a holistic, integrated approach to its management, considering affective, cognitive, behavioural, physical, and social dimensions to improve patients&#x2019; quality of life.<br><br>PRACTICAL IMPLICATIONS: Understanding the lived experiences of LC patients can guide healthcare services in providing more targeted, empathetic, and effective support.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-025-13469-z.},
}
@article {pmid41066748,
year = {2025},
author = {Tan, EC and Hsiao, FY and Yang, MC},
title = {The economic burden of COVID-19 in a region with stringent response measures: A case study of Taiwan.},
journal = {Journal of food and drug analysis},
volume = {33},
number = {3},
pages = {326-338},
pmid = {41066748},
issn = {2224-6614},
mesh = {Humans ; *COVID-19/economics/epidemiology ; Taiwan/epidemiology ; *Cost of Illness ; Middle Aged ; Adult ; Aged ; Female ; Male ; SARS-CoV-2 ; Young Adult ; Health Care Costs ; Adolescent ; Pandemics/economics ; Child ; Hospitalization/economics ; Child, Preschool ; },
abstract = {The COVID-19 pandemic has imposed a significant economic burden globally, particularly in regions with stringent response measures. This study aims to assess the economic impact of COVID-19 in Taiwan, focusing on both direct and indirect costs. A cost-of-illness analysis was conducted, utilizing data from the Taiwan Centers for Disease Control (CDC), national databases, epidemiological studies, and economic surveys. The analysis included both direct costs (e.g., hospital admissions, outpatient care) and indirect costs (e.g., productivity losses due to long COVID, absenteeism, caregiving duties). The study encompassed Taiwan's population of 23.2 million, with particular attention to age-specific impacts on economic outcomes. The total economic burden of COVID-19 in Taiwan was estimated at USD 4431 million. Direct costs accounted for 24.40% (USD 1081 million), while indirect costs constituted 75.60% (USD 3350 million). The working age population bore the majority of this burden, with 88.68% (USD 3090 million) of total costs attributed to this group. Long COVID significantly contributed to the economic impact, causing a 35% reduction in productivity. Sensitivity analysis revealed that the frequency of outpatient visits among working age and elderly cohorts was a critical factor influencing overall costs. The study underscores the substantial economic burden of stringent COVID-19 policies in Taiwan, highlighting that indirect costs were nearly three times higher than direct costs. The findings emphasize the need for resilient healthcare systems and support for affected workers, particularly in regions with similar response strategies. The methodological approach offers insights that could be applied to other regions facing similar challenges.},
}
@article {pmid41066438,
year = {2025},
author = {Stauffer, SR},
title = {The Same and Not the Same: Discovery of S-892216, A Second-Generation Nonpeptidic Covalent 3CL Protease Inhibitor for Oral COVID-19 Therapeutics.},
journal = {Journal of medicinal chemistry},
volume = {68},
number = {20},
pages = {21095-21098},
doi = {10.1021/acs.jmedchem.5c02784},
pmid = {41066438},
issn = {1520-4804},
mesh = {*COVID-19 Drug Treatment ; Humans ; *Coronavirus 3C Proteases/antagonists &amp; inhibitors/metabolism ; *SARS-CoV-2/drug effects/enzymology ; *Antiviral Agents/pharmacology/chemistry/administration &amp; dosage/therapeutic use ; Administration, Oral ; Drug Discovery ; *Protease Inhibitors/chemistry/pharmacology/therapeutic use/administration &amp; dosage ; Animals ; COVID-19 ; Structure-Activity Relationship ; },
abstract = {The COVID-19 pandemic underscored the critical need for effective antiviral therapeutics. While vaccines have been instrumental in mitigating disease severity, the emergence of variants and long-COVID symptoms highlight the ongoing importance of antiviral therapeutic interventions. Targeting the 3CL[pro] main protease has been successful in identifying clinical agents; however limited options exist, and improvements are still required to have broader clinical utility. Utilizing the established central scaffold to develop ensitrelvir, both noncovalent and covalent modes of action were leveraged using structural knowledge to identify S-892216 as a potential best-in-class reversible covalent nonpeptidic 3CL[pro] inhibitor with a superior preclinical profile for treatment of COVID-19 and future pandemic preparedness.},
}
@article {pmid41065846,
year = {2025},
author = {Chang, CC and Li, YH and Chen, HH and Sun, SF},
title = {Clinical applications and molecular mechanisms for intravenous laser blood irradiation: a systematic review.},
journal = {Lasers in medical science},
volume = {40},
number = {1},
pages = {416},
pmid = {41065846},
issn = {1435-604X},
support = {TSGH-D-110120//Tri-Service General Hospital/ ; VTA114-V3-1-2//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; VTA114-V3-1-1//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; KAFGH-ZY-A-113016//Zuoying Armed Forces General Hospital/ ; KSVGH-114-102//Kaohsiung Veterans General Hospital/ ; },
mesh = {Humans ; *Blood/radiation effects ; Cardiovascular Diseases/radiotherapy ; COVID-19 ; *Low-Level Light Therapy/methods ; Musculoskeletal Diseases/radiotherapy ; Nervous System Diseases/radiotherapy ; },
abstract = {Intravenous Laser Irradiation of Blood (ILIB) is a therapeutic approach that utilizes low-level laser energy to irradiate blood, showing potential clinical value in treating various diseases in recent years. This systematic review aims to comprehensively examine the basic principles, technological developments, biological effects, and clinical applications of ILIB, while analyzing the level of evidence and limitations of existing research. Through searching relevant literature in databases such as PubMed, this study collected research on ILIB applications in musculoskeletal diseases, respiratory diseases, cardiovascular diseases, and neurological disorders. Results indicate that ILIB exhibits multiple biological effects, including improved blood rheological properties, enhanced erythrocyte oxygen-carrying capacity, immune regulation, and reduction of inflammatory responses and oxidative stress. Clinical studies suggest that ILIB has positive therapeutic effects on musculoskeletal pain, sleep disorders, pulmonary diseases, and long COVID-related cognitive impairments. However, existing research still has limitations such as small sample sizes, lack of large-scale randomized controlled trials, and non-standardized dosage parameters. Future research should focus on developing standardized treatment protocols, exploring mechanisms of action in depth, and strategies for combining with conventional therapies to further establish ILIB's position in clinical practice.},
}
@article {pmid41064382,
year = {2025},
author = {Boyarchuk, O and Perestiuk, V and Kosovska, T and Volianska, L},
title = {Anti-interferon α-antibodies in pediatric patients with COVID-19 and long COVID.},
journal = {Reumatologia},
volume = {63},
number = {4},
pages = {229-235},
pmid = {41064382},
issn = {0034-6233},
abstract = {INTRODUCTION: The involvement of neutralizing antibodies against type I interferon (IFN-I) in the development of severe coronavirus disease 2019 (COVID-19) in adult patients has been well documented. However, the role of anti-IFN-α autoantibodies, especially non-neutralizing types, remains underexplored, especially in children. Our study aimed to determine the frequency of antibodies against IFN-α in children with COVID-19 and long COVID, as well as their potential role in the development of long COVID.<br><br>MATERIAL AND METHODS: The study included 78 children aged 1 to 17 years with a documented history of COVID-19 from September 2022 to August 2023. All patients were divided into three groups: hospitalized with COVID-19, hospitalized with long COVID symptoms, and monitored in an outpatient care department for mild COVID-19 or symptoms of long COVID. Human anti-IFN-&#x3b1; antibodies were detected using enzyme-linked immunosorbent assay.<br><br>RESULTS: Binding anti-IFN-&#x3b1; antibodies were detected in 2/78 (2.6%) children with COVID-19 of varying severity. One patient with anti-IFN-&#x3b1; antibodies had comorbidities (obesity, allergic rhinitis) and critical COVID-19 pneumonia (SpO2 - 80%), significant inflammatory changes (neutrophil-to-lymphocyte ratio: 18.8, C-reactive protein: 95.5 mg/l), and a high D-dimer level, and later developed long COVID symptoms. In the second case, COVID-19 in a 13-year-old girl without significant comorbidities was not severe, but leukopenia and lymphopenia were observed. Subsequently, she developed pronounced long COVID symptoms (fatigue, reduced appetite, insomnia, headache, decreased attention, difficulty concentrating, weight loss, tachycardia, dizziness), which persisted for up to 6 months after the acute infection. The detection rate of binding anti-IFN-&#x3b1; antibodies among hospitalized COVID-19 patients was 4%, compared to 25% among patients with severe/critical disease. Among children who developed long COVID symptoms, anti-IFN-&#x3b1; was found in 3.4%.<br><br>CONCLUSIONS: Further studies in larger cohorts are needed to assess the role of anti-IFN-&#x3b1; antibodies (both neutralizing and non-neutralizing) in the development of long COVID symptoms, to understand their clinical significance, and to examine their dynamics over time.},
}
@article {pmid41062803,
year = {2025},
author = {Aboagye, NY and Hinchliffe, C and Del Din, S and Ng, WF and Baker, KF and Baker, MR},
title = {Systematic review: digital biomarkers of fatigue in chronic diseases.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {602},
pmid = {41062803},
issn = {2398-6352},
support = {853981//Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) project IDEA-FAST/ ; 853981//Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) project IDEA-FAST/ ; 853981//Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) project IDEA-FAST/ ; CRFC-2021-005/HRBI_/Health Research Board/Ireland ; EP/X036146/1//Engineering and Physical Sciences Research Council/ ; NIHR303620//National Institute for Health and Care Research/ ; COV-LT2-022//National Institute for Health and Care Research/ ; },
abstract = {This systematic review explores the relationship between digital biomarkers, measured using wearable devices, and fatigue in patients with chronic diseases. Studies included in this review focused on individuals with diseases or conditions in 13 broad categories: multiple sclerosis (MS); rheumatoid arthritis (RA); chronic obstructive pulmonary disease (COPD); long COVID; cancer; chronic fatigue syndrome (CFS); pulmonary sarcoidosis; Parkinson's disease; chronic stroke; chronic inflammatory rheumatic disease (CIRD); Inflammatory Bowel Diseases (IBD), Primary Sjogren's Syndrome (PSS), and Systemic Lupus Erythematosus (SLE). The review synthesizes findings on the correlation between objective digital biomarkers and self-reported fatigue, highlighting the potential for disease-specific digital biomarkers to inform personalized fatigue management. The results suggest that reduced physical activity, increased sedentary behavior and autonomic dysfunction are associated with fatigue levels across multiple disease conditions included in this review, though the strength of this association and the specific biomarkers involved vary across diseases.},
}
@article {pmid41062137,
year = {2025},
author = {Daniels, S and Wei, H and McElvenny, DM and van Tongeren, M and Bramwell, D and Coleman, A and Forde, D and Wiggans, R},
title = {Return to work with long COVID: a rapid review of support and challenges.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e101698},
pmid = {41062137},
issn = {2044-6055},
mesh = {Humans ; *Return to Work ; Workplace ; *Post-Acute COVID-19 Syndrome/rehabilitation ; },
abstract = {OBJECTIVES: To explore existing evidence for the provision of support for return to work (RTW) in long COVID (LC) patients and the barriers and facilitators to taking up this support.<br><br>DESIGN: A rapid review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study was preregistered in PROSPERO (ID: CRD42023478126).<br><br>DATA SOURCES: Searches were completed in June 2024 across major databases including MEDLINE, Embase, PsycINFO, evidence-based medicine reviews, Web of Science and Google Scholar.<br><br>ELIGIBILITY CRITERIA: Included studies focused on people with LC (PwLC) symptoms lasting over 12 weeks and addressed either: (1) non-workplace- or workplace-based support for RTW and/or (2) barriers and facilitators to RTW in this population.<br><br>DATA EXTRACTION AND SYNTHESIS: A quality assessment was conducted using the JBI Systematic Reviews critical appraisal tool. The data were summarised in tabular format and a narrative synthesis.<br><br>RESULTS: Twenty-five studies were included. While many studies demonstrated rigorous methodologies and low risk of bias levels, some had high and medium risk levels. Non-workplace-based support was mostly measured quantitatively and included interdisciplinary healthcare programmes, clinical interventions and rehabilitation programmes focusing on pacing and breathing strategies. Compensation and insurance schemes were important funders of these interventions.Workplace-based support was mostly measured qualitatively. Barriers to the provision of support at organisational level included lack of understanding of LC symptoms, insufficient workplace guidance and educational gaps among managers. Individual barriers included threat of income loss, remote working and disconnection from the workplace. Facilitators for support included recognition and validation of LC and its symptoms, and eligibility for disability benefits associated with work.<br><br>CONCLUSIONS: RTW is an important outcome of health-related absence and should be systematically recorded in studies of PwLC. The heterogeneity and unpredictability of LC symptoms create challenges for supporting working age populations. Further research is crucial to better understand the specific RTW needs for PwLC and address potential barriers and facilitators to workplace-based support, particularly through interventions, organisational practices and employ-led policies that enable sustained RTW. Consistent guidelines on LC's definition and disability status may facilitate the provision of support and the development of interventions.<br><br>PROSPERO REGISTRATION NUMBER: CRD42023478126.},
}
@article {pmid41059474,
year = {2025},
author = {Perestiuk, V and Kosovska, T and Volianska, L and Boyarchuk, O},
title = {Prevalence and duration of clinical symptoms of pediatric long COVID: findings from a one-year prospective study.},
journal = {Frontiers in pediatrics},
volume = {13},
number = {},
pages = {1645228},
pmid = {41059474},
issn = {2296-2360},
abstract = {BACKGROUND: Long COVID in children remains a poorly understood condition with wide variability in clinical presentation, duration, and risk factors. The aim of this study was to assess the prevalence, spectrum, and duration of long COVID symptoms in pediatric patients following acute SARS-CoV-2 infection using a standardized follow-up tool.<br><br>METHODS: We conducted a prospective cohort study involving 127 unvaccinated children aged 1 month to 18 years with long COVID according to the WHO definition and confirmed SARS-CoV-2 infection. Participants were followed up at 1-3, 3-6, 6-9, and 9-12 months post-infection using an adapted ISARIC Global Pediatric COVID-19 Follow-Up Questionnaire.<br><br>RESULTS: Persistent symptoms of long COVID were reported in 85.8% of patients at 3 months, decreasing to 56.1% at 9 months and 32.5% at 12 months. The most common long-term symptoms included fatigue (52.0%), reduced physical activity (44.1%), and headache (35.3%). Multivariable logistic regression showed that older age was significantly associated with a higher risk of decreased physical activity (OR&#x2009;=&#x2009;1.51, p&#x2009;=&#x2009;0.038), lack of energy (OR&#x2009;=&#x2009;2.00, p&#x2009;=&#x2009;0.003), neurological symptoms (OR&#x2009;=&#x2009;1.86, p&#x2009;=&#x2009;0.007), headache (OR&#x2009;=&#x2009;4.51, p&#x2009;=&#x2009;0.000), memory impairment (OR&#x2009;=&#x2009;5.12, p&#x2009;=&#x2009;0.000), difficulty communicating (OR&#x2009;=&#x2009;4.28, p&#x2009;=&#x2009;0.000), difficulty concentrating (OR&#x2009;=&#x2009;2.74, p&#x2009;=&#x2009;0.001), cardiological symptoms (OR&#x2009;=&#x2009;2.34, p&#x2009;=&#x2009;0.022), sensory symptoms (OR&#x2009;=&#x2009;2.66, p&#x2009;=&#x2009;0.011), and dizziness (OR&#x2009;=&#x2009;10.02, p&#x2009;=&#x2009;0.034). Younger age was associated with insomnia (OR&#x2009;=&#x2009;0.49, p&#x2009;=&#x2009;0.018). Female sex was significantly associated with a greater likelihood of lack of energy (OR&#x2009;=&#x2009;2.55, p&#x2009;=&#x2009;0.048). Hospitalization status was only significantly associated with muscle pain, with outpatients more frequently affected (OR&#x2009;=&#x2009;0.28, p&#x2009;=&#x2009;0.029).Overall, 32.5% of all participants continued to experience symptoms of long COVID more than one year acute infection, with fatigue persisting in 19.8%, reduced physical activity in 13.9%, headache in 12.3%.<br><br>CONCLUSIONS: Long COVID affects children across all age groups and may persist beyond one year in a significant subset. These findings highlight age- and sex-specific symptom profiles and underscore the need for structured pediatric follow-up.},
}
@article {pmid41057923,
year = {2025},
author = {Gidey, K and Niriayo, YL and Asgedom, SW and Lubetkin, E},
title = {Health-related quality of life in COVID-19 patients: a systematic review and meta-analysis of EQ-5D studies.},
journal = {Health and quality of life outcomes},
volume = {23},
number = {1},
pages = {97},
pmid = {41057923},
issn = {1477-7525},
support = {1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; },
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/psychology ; SARS-CoV-2 ; Female ; Male ; Health Status ; },
abstract = {BACKGROUND: COVID-19 has affected millions globally, with a significant proportion experiencing long-COVID and impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to synthesize the existing literature on HRQoL in COVID-19 patients.<br><br>METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for studies published between December 2019 and March 2025. Eligible studies were peer-reviewed and assessed HRQoL in COVID-19 patients using the EQ-5D instrument. Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale. Pooled health utility values were estimated using a random-effects model, and heterogeneity was assessed via I[2] statistics. Predictors of poor HRQoL were qualitatively narrated.<br><br>RESULTS: Out of 3539 references, 187 studies with 116,525 participants were analyzed. The majority (80.2%) used the EQ-5D-5&#xa0;L version. The pooled mean EQ-5D utility score was 0.76 (95% CI 0.74-0.79, I[2] = 99.9%) while the mean EQ-5D Visual Analogue Scale (VAS) score was 70.76 (95% CI 68.48-73.04; I[2] = 99.7%). Pain/discomfort and anxiety/depression were the most affected domains, reported by 51% and 46% of patients, respectively. Subgroup analysis showed significant differences in HRQoL based on national income status (p&#x2009;=&#x2009;0.038) and geographic region (p&#x2009;<&#x2009;0.001). Common predictors of lower HRQoL included older age, female gender, disease severity, comorbidities, and post-COVID-19 symptoms.<br><br>CONCLUSION: This systematic review demonstrates a substantial reduction in HRQoL among COVID-19 patients compared to the general population. The pooled utility values of COVID-19 contribute to understanding patients' HRQoL and can assist in calculating Quality-Adjusted Life Years. This provides essential data for future economic evaluations and informs health policy decisions.},
}
@article {pmid41057797,
year = {2025},
author = {Bessaguet, C and Bonilla, A and Polin, C and Lacroix, A and Cartz-Piver, L},
title = {A systematic review to find link between past psychiatric history and development of long covid.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {942},
pmid = {41057797},
issn = {1471-244X},
mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; *Mental Disorders/epidemiology/psychology/complications ; Risk Factors ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Anxiety/epidemiology/psychology ; *Depression/epidemiology ; },
abstract = {BACKGROUND: Covid-19 is a pandemic acute infectious disease that emerged in 2019. It is estimated that 10-20% will develop persistent symptoms, known as long Covid or post-Covid syndrome. The risk factors for the development of this syndrome are still being studied. Psychosocial factors are known to increase the duration and severity of respiratory infections.<br><br>AIMS: (i) to review current knowledge of the link between past psychiatric history and the development of long Covid; (ii) to obtain information on the psychological experience of the initial infection; (iii) to establish a link between the presence of psychiatric symptoms during the acute phase and the development of long Covid.<br><br>METHOD: We conducted a systematic review according to PRISMA standards using the Pubmed, Science Direct and Scopus databases. We included observational studies of adult subjects with long Covid whose psychiatric and/or addictive histories were searched.<br><br>RESULTS: A total of 36 articles were included in our review. Depression and anxiety appear to be risk factors for the development of long Covid. There is no consensus on the contribution of smoking to the onset of the syndrome. The negative psychological experience of the acute infection favours the persistence of symptoms. Psychological symptoms during the acute phase, studied in only one of our articles, seem to contribute to the persistence of concentration and attention problems.<br><br>CONCLUSION: Psychological comorbidities pre-existing COVID-19 infection, in particular depression and anxiety, as well as a poor psychological experience of the acute phase, may favour the development of long Covid.<br><br>TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42023391720.},
}
@article {pmid41056092,
year = {2025},
author = {Newby, MJ and Haracz, K and Lane, SJ and Tona, J},
title = {Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Occupational Performance: A Scoping Review.},
journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association},
volume = {79},
number = {6},
pages = {},
doi = {10.5014/ajot.2025.051238},
pmid = {41056092},
issn = {0272-9490},
mesh = {Humans ; *Occupational Therapy/methods ; Child ; *Obsessive-Compulsive Disorder/rehabilitation ; *Activities of Daily Living ; Social Participation ; Autoimmune Diseases ; },
abstract = {IMPORTANCE: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a neuroimmune condition that significantly affects children's occupational performance across multiple domains. However, occupational performance is often overlooked in current PANS clinical frameworks, despite its critical role in daily functioning and well-being.<br><br>OBJECTIVE: To synthesize evidence on the occupational performance challenges experienced by children with PANS, the tools used to assess these challenges, and occupational therapy interventions used with these children.<br><br>DATA SOURCES: MEDLINE, CINAHL, Cochrane Library, PsycINFO, SCOPUS, ERIC, and EMBASE were searched from their inception through May 17, 2024.<br><br>Peer-reviewed studies addressing PANS and occupational performance were included, with data categorized using the Occupational Therapy Practice Framework, 4th Edition.<br><br>FINDINGS: Of 3,431 records, 40 studies met inclusion criteria. Occupational performance challenges centered on communication, nutrition, education, rest/sleep, social participation, and toileting, with limited data on bathing, dressing, personal hygiene, and play and leisure. Assessments emphasized client factors, rarely using occupation-based tools. Only 2 studies mentioned occupational therapy interventions.<br><br>CONCLUSIONS AND RELEVANCE: PANS has a pervasive impact on children's occupational performance, highlighting the urgent need to prioritize it within clinical frameworks. Future research should focus on occupation-based intervention studies and assessments to enhance outcomes for children with PANS. Plain-Language Summary: Pediatric acute-onset neuropsychiatric syndrome (PANS) causes sudden, severe symptoms, such as obsessive-compulsive behaviors, eating difficulties, sensory and motor changes, and developmental regression, which significantly disrupt children's ability to perform daily activities. This study included 40 research articles addressing what is known about the impact of PANS on children's daily functioning and the role of occupational therapy in managing challenges. Results showed that most studies focused on communication, nutrition, education, sleep, social, and toileting challenges, but few addressed other daily tasks like bathing, dressing, personal hygiene, and play or leisure. Despite identified challenges, only two studies mentioned occupational therapy interventions, highlighting a major gap in the evidence. Assessments focused mainly on a child's skills and challenges, rather than looking at how the child participates in everyday activities. The findings highlight the need to better understand the challenges children with PANS face in their everyday activities and to provide practical strategies to help them succeed. Positionality Statement: Newby is a pediatric occupational therapist and researcher with both professional and personal experience of PANS. Her clinical work with children diagnosed with PANS, along with personal experience supporting a family member with this condition, has deepened her interest in the episodic fluctuations in occupational performance that occur during periods of exacerbation and remission. Haracz is an occupational therapist, academic, and researcher with a focus on mental health and the intersection between physical and psychological well-being. Lane is an occupational therapist, academic, and researcher who specializes in the neuroscience of developmental conditions and how sensory processing differences affect children's engagement in daily occupations. Tona is an occupational therapist and educational psychologist whose interest in neuroinflammatory disorders emerged following a family member's diagnosis with PANS. Her research explores the characteristics of PANS, treatment access, caregiver burden, and the role of occupational therapy in improving participation in both PANS and long-COVID populations.},
}
@article {pmid41054864,
year = {2025},
author = {Bredström, A and Jämterud, SM},
title = {Post Covid-19 Condition as a Diagnosis: A Qualitative Study on Epistemological Tensions Among Experts in Sweden.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70463},
pmid = {41054864},
issn = {1369-7625},
support = {//The project is part of an interdisciplinary project, Biomedicine, Clinical Knowledge, and the Humanities in Collaboration: A Novel Epistemology for Radically Interdisciplinary Health Research and Policy-Work on Post COVID-19 Syndrome, funded by the Swedish Research Council (Vetenskapsr&#xe5;det, grant number 2021-01245)./ ; },
mesh = {Humans ; Sweden ; *COVID-19/complications/diagnosis ; Qualitative Research ; Female ; Male ; Interviews as Topic ; SARS-CoV-2 ; Middle Aged ; Adult ; *Knowledge ; },
abstract = {BACKGROUND: At the onset of the Covid-19 pandemic, it became clear that some individuals experienced lingering symptoms after the infection. This condition, known as post Covid-19 condition (or long Covid), is defined by WHO as persistent or new symptoms 3 months after the initial infection, lasting for at least 2 months, and not attributable to another diagnosis. Hence, the definition is very broad.<br><br>AIM: This study aims to examine how post Covid-19 condition as a diagnosis is viewed and interpreted by Swedish stakeholders, showing how these understandings carry a range of epistemological tensions. The study also seeks to understand the implications of these epistemological tensions for treatment and care organisation.<br><br>METHODS: Qualitative interviews with 36 experts and key individuals in Sweden have been conducted.<br><br>RESULT: Experts agree that post Covid-19 condition is a complex syndrome and that persons who suffer are in need of care. However, several tensions in post Covid-19 condition as a diagnosis can be discerned. Most experts agreed on the gender and racial disparity where white women with Swedish background were a majority of post Covid-19 sufferers, while migrant patients and the elderly are largely absent. In relation to social categories, the question if children can have post Covid-19 condition is here a highly contested question. There is also disagreement on the aetiology of post Covid-19 condition, with some experts viewing it as a new, unique condition requiring specialised treatment, while others see it as similar to other post-viral conditions, treatable in primary care.<br><br>CONCLUSION: The article concludes that experts are divided in their understanding and that this affects Swedish policy on post Covid-19 care and treatment, showing that post Covid-19 condition is not only a medical issue but also a political battleground where science, expert opinion and patient experience shape policy.<br><br>The article focuses on studying stakeholders' perspectives as these are key for informing public opinion and policy. In this article, all main organisations and authorities involved in post Covid-19 care are represented. We also see patients as crucial stakeholders and representatives of patient organisations, as well as representatives of some migrant communities, who have been interviewed. The latter were included to gain insights from groups that were largely absent in post Covid-19 care.},
}
@article {pmid41054219,
year = {2025},
author = {Hudson, N and Hannah, S and Husted, M and Fryer, S and Ryan-Stewart, H and Rickenbach, M and Stone, K and Faulkner, J},
title = {The effect of uninterrupted and interrupted sitting on vascular function in adults with long COVID.},
journal = {Physiological reports},
volume = {13},
number = {19},
pages = {e70452},
doi = {10.14814/phy2.70452},
pmid = {41054219},
issn = {2051-817X},
support = {UoA23_22_Faulk//University of Winchester (UoW)/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/complications ; *Sitting Position ; Adult ; *Blood Pressure/physiology ; *Vascular Stiffness/physiology ; *Exercise/physiology ; Middle Aged ; Sedentary Behavior ; Pulse Wave Analysis ; Carotid-Femoral Pulse Wave Velocity ; SARS-CoV-2 ; },
abstract = {Acute prolonged sitting increases blood pressure (BP) and arterial stiffness (AS). Both of these may be mitigated via light physical activity (LPA). Whether long COVID (LC), which partly manifests as vascular sequelae, predisposes a heightened sensitivity to sitting or diminished benefits from its interruption is unknown. The aims of this study were to identify whether individuals with LC: (i) exhibit a worse BP/AS response to uninterrupted sitting and (ii) a diminished mitigation of BP/AS response to sitting interrupted with LPA, compared to healthy controls. Thirty participants with LC and 15 controls completed 2 h of uninterrupted sitting and sitting interrupted with LPA. Central and peripheral systolic and diastolic BP and carotid-femoral pulse wave velocity (cfPWV) were determined pre and post sitting. Linear mixed-effects models demonstrated no three-way or two-way interactions for any variable. There was a significant main effect of time, with increases in central systolic (MD = 3.37 mmHg, SE = 0.93 mmHg, p < 0.001) and central diastolic (MD = 3.00 mmHg, SE = 0.58 mmHg, p < 0.001) BP. cfPWV was not altered in sitting in either group (MD = 0.13 m/s, SE = 0.09 m/s, p = 0.170). Uninterrupted sitting increases BP similarly, but AS is unchanged. Interrupting sitting with LPA did not mitigate sitting-induced increase in BP regardless of LC diagnosis.},
}
@article {pmid41051570,
year = {2025},
author = {Zadeh, S and Robbins, N and Hernandez, R and Bryarly, M and Vernino, S},
title = {Letter to the editor regarding "Chronic autonomic symptom burden in long-COVID: a follow-up cohort study.".},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {},
number = {},
pages = {},
pmid = {41051570},
issn = {1619-1560},
}
@article {pmid41050528,
year = {2025},
author = {Kranck, G and Ståhlberg, M and Andersson, U and Lundin, J and Fedorowski, A},
title = {Monitoring of cardiorespiratory vagal desynchrony using novel biomarkers derived from smartwatch electrocardiograms in a patient recovering from long COVID: case report.},
journal = {European heart journal. Case reports},
volume = {9},
number = {10},
pages = {ytaf425},
pmid = {41050528},
issn = {2514-2119},
abstract = {BACKGROUND: Long COVID and cardiovascular autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), present significant healthcare challenges. Long-term monitoring is challenging due to the evolving nature of symptoms and the limited availability of objective diagnostic tools. With over 200 million electrocardiogram (ECG)-enabled smartwatches sold worldwide, these devices offer a promising solution for at-home diagnostics and disease tracking.<br><br>METHODS AND RESULTS: This study examines a 35-year-old male with long COVID, POTS, and chronic fatigue syndrome (CFS), who recorded 328 ECGs over using a Samsung smartwatch. The protocol required ECG recordings to be taken first in a sitting posture, followed by a standing position, with slow, controlled breathing. For testing, the patient used a Samsung smartwatch to perform a 30-s hand-to-hand single-lead ECG while engaging in 0.1&#x2005;Hz diaphragmatic controlled breathing, consisting of 5&#x2005;s of inhalation followed by 5&#x2005;s of exhalation (Appendix 1). S-/R-peak amplitude ratios, heart rhythm changes, and other biomarkers were analysed to assess autonomic function. Fatigue levels were self-reported via the BREATHE FLOW app using a three-grade scale, and health status was tracked monthly with the EQ-5D-5L model. Initially, the patient experienced severe fatigue and heart rhythm changes consistent with POTS. Electrocardiogram analysis revealed an increased S-wave amplitude and higher S/R ratio in standing posture, along with worsening respiratory sinus arrhythmia (RSA), indicating cardiorespiratory desynchrony. Over time, as symptoms improved, heart rate responses between sitting and standing normalized, and S/R ratio and RSA index followed self-reported fatigue levels, including fluctuations due to post-exercise fatigue.<br><br>CONCLUSION: Smartwatch-derived S-/R-wave amplitude ratio may serve as an accessible biomarker for tracking disease progression in long COVID. Given the widespread availability of smartwatches, standardized at-home protocols could improve diagnostics and monitoring for autonomic dysfunction.},
}
@article {pmid41049923,
year = {2025},
author = {Pedraza, A and Bonnice, S and Won, MN and Kesselman, MM and Demory Beckler, M},
title = {Impact of COVID-19 on the Gut Microbiome: A Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91470},
pmid = {41049923},
issn = {2168-8184},
abstract = {Coronavirus Disease 2019 (COVID-19) has resulted in over 6 million deaths worldwide in fewer than four years and is a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The protein that mediates SARS-CoV-2 host cell entry is the angiotensin-converting enzyme 2 (ACE2), which is highly expressed on the membrane of gastrointestinal (GI) cells. Consequently, infection can lead to direct damage to the GI tract and gut dysbiosis, which is associated with an imbalance of microbiota, inflammation, and other systemic infections and diseases. In this review, we will focus on the impact of COVID-19 on the GI system. We will examine the pathophysiology of gut dysbiosis in COVID-19 patients, as well as emphasize the significance of probiotics in addressing this condition. Additionally, we will identify key areas of interest that warrant further investigation.},
}
@article {pmid41049897,
year = {2025},
author = {Castellano, B and Castellano, C and Sobczak, A and Khanna, D},
title = {Long-Term Manifestations of COVID-19: A Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91492},
pmid = {41049897},
issn = {2168-8184},
abstract = {Although most coronavirus disease 2019 (COVID-19) cases resolve within a few weeks after the onset of infection, a considerable number of patients still suffer from prolonged or recurrent symptoms evident after weeks or months post-COVID-19 recovery. This paper analyzed the current literature related to long-term manifestations of COVID-19 and aimed to identify the common symptoms reported four weeks or more after the initial onset of the disease. COVID-19 has been shown to have lasting systemic effects on an array of organ systems, such as the lungs, heart, brain, and gastrointestinal systems. Common symptoms include, but are not limited to, fatigue, brain fog, respiratory difficulties, and loss of taste and smell. The impact of COVID-19 on multiple organ systems is thought to be associated with its ability to bind angiotensin-converting enzyme 2 (ACE2) receptors throughout the body and promote cytokine release. This study provides insight into common long-term manifestations of COVID-19. Future studies should look at how long COVID-19 syndrome affects various subpopulations differently.},
}
@article {pmid41048268,
year = {2025},
author = {Dale, Z and Wallington, SF and Penn-Marshall, M},
title = {Prevalence and characteristics of post-acute sequelae of COVID-19 in recovered patients.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1648961},
pmid = {41048268},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Risk Factors ; Adult ; Texas/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; Comorbidity ; },
abstract = {INTRODUCTION: Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection, has emerged as a major public health concern following the COVID-19 pandemic. Although initially perceived as a respiratory illness, growing biomedical evidence confirms that COVID-19 affects multiple organ systems. This study aimed to explore the clinical manifestations, risk factors, and long-term outcomes associated with long COVID and to identify patients at highest risk. The research also contributes to the ongoing discourse on establishing a unified definition of long COVID.<br><br>METHODS: A secondary analysis of a cross-sectional, community-based study was conducted using data from 168 households, representing a weighted total of 14,769 households in Third Ward, Houston, Texas. Data were collected via interviewer-administered surveys and included variables on demographics, pre-existing comorbidities, COVID-19 symptom severity, and post-acute symptom persistence. Symptom variables were recoded as binary indicators, and weighted logistic regression models were applied to identify associations between acute phase characteristics and the development of long COVID.<br><br>RESULTS: Risk factors significantly associated with long COVID included symptom severity during acute infection (OR&#x202f;=&#x202f;29.58, 95% CI [1.38, 632.53]), heart disease (OR&#x202f;=&#x202f;6.00, 95% CI [1.15, 31.28]), asthma (OR&#x202f;=&#x202f;3.49, 95% CI [1.05, 11.59]), and poor physical health (OR&#x202f;=&#x202f;4.20, 95% CI [1.12, 15.75]). Acute symptoms predictive of long COVID included anxiety (OR&#x202f;=&#x202f;22.94, 95% CI [2.01, 262.31]), chest pain (OR&#x202f;=&#x202f;7.15, 95% CI [1.13, 45.23]), constipation (OR&#x202f;=&#x202f;16.81, 95% CI [1.33, 213.23]), heart palpitations (OR&#x202f;=&#x202f;6.59, 95% CI [1.08, 40.18]), and shortness of breath (OR&#x202f;=&#x202f;4.97, 95% CI [1.16, 21.36]). No statistically significant associations were found between long COVID and race, education, or income.<br><br>CONCLUSION: The findings underscore the multisystemic nature of long COVID, characterized by a diverse range of symptoms including fatigue, cognitive impairment, shortness of breath, and neuropsychiatric issues such as depression. While clinical factors are critical in understanding long COVID, the results also suggest that addressing associated health outcomes requires broader consideration of social determinants of health.},
}
@article {pmid41048263,
year = {2025},
author = {Verma, A and Naidu, SV and Sulthana, H and Ullah, A and Shabil, M and Sah, R and Mehta, R and Jan, A and Ain, NU and Rahim, A and Abu Nahla, U},
title = {Musculoskeletal manifestations in post-acute sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1662953},
pmid = {41048263},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Musculoskeletal Diseases/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Incidence ; Myalgia/epidemiology ; },
abstract = {BACKGROUND: The COVID-19 pandemic has highlighted a spectrum of long-term sequelae, with musculoskeletal symptoms being a substantial component of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). This systematic review and meta-analysis aimed to evaluate the incidence and nature of musculoskeletal manifestations in individuals recovering from COVID-19.<br><br>METHODS: A systematic search across PubMed, Embase, and Web of Science was performed up to February 15, 2024, to identify studies reporting on musculoskeletal symptoms post-COVID-19. Observational studies which reported any musculoskeletal symptoms of PASC were included. Data were pooled using a random-effects model to calculate the incidence of symptoms, with subgroup analyses based on time since infection. Statistical analysis were conducted in R software (V 4.3).<br><br>RESULTS: Sixty-four studies were included, demonstrating a pooled prevalence of muscle pain at 28% (95% CI: 22%-35%), which increased to 25.9% (95% CI: 20.7%-31.7%) at 12 months post-infection. Joint pain showed a pooled prevalence of 14.8% (95% CI: 10.6%-20.2%), with no significant temporal change. Muscle weakness was observed in 12.9% (95% CI: 4.2%-32.9%) of patients. Notable heterogeneity was observed across studies (I [2] > 89% for all symptoms).<br><br>CONCLUSION: Musculoskeletal symptoms are prevalent in individuals with PASC, with muscle pain being the most common. The findings highlight the need for comprehensive clinical management and continuous research to create targeted treatments and revise care protocols as the pandemic evolves.},
}
@article {pmid41046766,
year = {2025},
author = {Reséndiz-Vazquez, J and Domínguez-Reyes, V and Terán-Paredes, E and Madero-Franco, N and Chávez-González, A and Majluf-Cruz, A and Alvarado-Moreno, JA},
title = {Deep Venous Thrombosis in Patients Recovered from COVID-19: A Long-Term Sequel.},
journal = {Archives of medical research},
volume = {57},
number = {3},
pages = {103305},
doi = {10.1016/j.arcmed.2025.103305},
pmid = {41046766},
issn = {1873-5487},
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19 disease has the ability to generate sequelae that extend for weeks or months, giving rise to long-term COVID-19 disease. This condition reduces patients' quality of life and predisposes them to several alterations, including failures in the blood coagulation system. Our laboratory has previously demonstrated abnormalities in endothelial colony-forming cells (ECFCs) of patients recovered from COVID-19.<br><br>OBJECTIVE: To analyze the functional state of ECFCs in patients who experienced venous thromboembolic disease (VTD) or arterial thrombosis (AT) during long COVID-19, or post-COVID condition (PCC).<br><br>METHODS: We compared 35 samples of peripheral blood (PB) mononuclear cells (MNCs) from patients with a thrombotic event (who had a healthy lifestyle before infection and were vaccinated) with 10 healthy volunteers and 10 samples from patients with a history of recurrent unprovoked VTD (rVTD) after a COVID-19 infection. The samples were cryopreserved in our laboratory and matched by age 25-50 years old and sex. The frequency, morphological characteristics, proliferation and angiogenic ability of ECFCs were evaluated in all samples.<br><br>RESULTS: There were no significant differences between male and female patients, and the laboratory data did not indicate risk factors for VTD or AT. The frequency of ECFCs was not different between controls and patients, but a reduced proliferative capacity, a high percentage of senescence and non-angiogenic activity were observed in VTD samples.<br><br>CONCLUSIONS: Our results demonstrate a strong association between VTD events in patients with PCC who had a healthy lifestyle prior to infection and ECFCs dysfunction.},
}
@article {pmid41044760,
year = {2025},
author = {Lillieberg, E and Ertzgaard, P and Fernlund, E and Duchen, K and Rytterström, P and Angelhoff, C},
title = {Experiences of living with long COVID during childhood and adolescence: a qualitative study from the child's perspective.},
journal = {BMC pediatrics},
volume = {25},
number = {1},
pages = {754},
pmid = {41044760},
issn = {1471-2431},
mesh = {Humans ; Child ; Adolescent ; Qualitative Research ; *COVID-19/psychology ; Male ; Female ; Adaptation, Psychological ; Interviews as Topic ; Chronic Disease ; Fatigue/psychology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: In February 2023, the World Health Organization (WHO) defined long COVID in children, highlighting limited knowledge about its psychosocial impact. Studies show it as a complex, long-lasting condition affecting multiple systems. WHO and researchers emphasise the need for more understanding, particularly its effect on daily life. The aim of this study was to explore how life is experienced and how it changed whilst living with long COVID during childhood.<br><br>METHODS: We present a qualitative study with an inductive and exploratory approach. Between October 2022 and March 2024, 16 children between 9 and 18 years old diagnosed with long COVID were interviewed face-to-face using a semi-structured interview guide. The results were analysed using reflexive thematic analysis by Braun and Clarke.<br><br>RESULTS: The results present the subjective reality of children suffering from long COVID and their struggle in daily life. The findings are presented through three themes: Losing my foothold, Fatigue decides my path, and My way forward, illustrating a temporal and emotional journey, reflecting how children make sense of their experiences, adapt to the persistent impact of long COVID, and gradually move toward acceptance.<br><br>CONCLUSIONS: This study addresses the lack of knowledge of long COVID in the society, how it affects children in their struggle to find a new path in life. It also shows that, with knowledge and support, the symptoms and the burden of the condition can decrease or even pass. It is important that people around these children, including health care, school and family, use this knowledge to promote health and avoid educational, health and social problems at a vulnerable time in life.},
}
@article {pmid41044528,
year = {2025},
author = {Portela, MC and Lima, SML and Escosteguy, CC and Martins, M and de Vasconcellos, MTL and Caldas, BDN and Bernardino, M and Baginski, NP and Góes, G and Sabaine, B and Furtado, D and Cavalcanti, M and Soares, L and Stelson, E and Singer, S and Cornish, F and Aveling, EL},
title = {Long COVID in the population of COVID-19 hospitalized patients discharged from SUS' hospitals in Rio de Janeiro City, Brazil: a patient-engaged cohort survey study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1232},
pmid = {41044528},
issn = {1471-2334},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/complications ; Female ; Male ; Middle Aged ; Adult ; SARS-CoV-2 ; Aged ; Cohort Studies ; Prevalence ; Hospitalization ; Surveys and Questionnaires ; Hospitals, Public ; Patient Discharge ; Young Adult ; Self Report ; },
abstract = {BACKGROUND: Long COVID (LC) is a global health concern, affecting millions and placing significant strain on healthcare systems. However, there is a notable lack of LC research in low- and middle-income countries, particularly in the global south. This study aims to fill this gap by focusing on Brazil, a country with an emerging LC literature but limited population estimates due to sampling constraints. Our unique focus is to estimate the prevalence of persistent symptoms and LC self-reported diagnosis among COVID-19 patients hospitalized in Rio de Janeiro City public hospitals. We also aim to identify factors associated with the LC measures and most frequent symptoms, providing valuable insights for healthcare systems and policymakers.<br><br>METHODS: We designed a comprehensive, patient-engaged cohort survey study to assess LC symptoms and administered it to a probability sample of adults six to 24 months post-discharge from public hospitals in Rio de Janeiro City. LC was measured as (i) at least one persistent symptom or (ii) self-reported LC. Among the symptoms, we considered post-exertional malaise, which is frequently neglected in LC studies. Additionally, we applied an adaptation of the DePaul Symptom Questionnaire to account not only for the presence but also the frequency of symptom occurrence. We estimate the prevalence of symptoms and use logistic regression models to identify associations between LC and the most frequent LC symptoms and independent variables, assessing demographic, socioeconomic, lifestyle, and clinical characteristics, vaccination, and severity of acute disease.<br><br>RESULTS: Results indicate the predominant study's focus on low-income and highly vulnerable people, with an elevated prevalence of comorbidities before LC. In the study population of 11,328 persons, 71.3% (95%CI 66.3; 76.2) reported frequently experiencing at least one persistent symptom, and 39.3% (95%CI 34.2; 44.4) self-reported having LC. The most frequent symptoms were fatigue, post-exertional malaise, joint pain, sleep disturbance, and cognitive impairment, and symptoms were consistently more likely to occur among women. Age was non-linearly related to LC, and comorbidities before COVID-19 hospitalization were positively associated with LC symptoms.<br><br>CONCLUSIONS: Evidence is provided for the LC burden among COVID-19 hospitalized patients even 24 months post-discharge. LC accessible and appropriate healthcare is fundamental.},
}
@article {pmid41043444,
year = {2026},
author = {Buonsenso, D},
title = {Long COVID is here to stay-even in children.},
journal = {The Lancet. Infectious diseases},
volume = {26},
number = {2},
pages = {112-113},
doi = {10.1016/S1473-3099(25)00496-7},
pmid = {41043444},
issn = {1474-4457},
}
@article {pmid41043442,
year = {2026},
author = {Zhang, B and Wu, Q and Jhaveri, R and Zhou, T and Becich, MJ and Bisyuk, Y and Blanceró, F and Chrischilles, EA and Chuang, CH and Cowell, LG and Fort, D and Horowitz, CR and Kim, S and Ladino, N and Liebovitz, DM and Liu, M and Mosa, ASM and Schwenk, HT and Suresh, S and Taylor, BW and Williams, DA and Morris, JS and Forrest, CB and Chen, Y and , },
title = {Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study.},
journal = {The Lancet. Infectious diseases},
volume = {26},
number = {2},
pages = {127-138},
pmid = {41043442},
issn = {1474-4457},
support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Adolescent ; *COVID-19/complications/epidemiology/virology ; Retrospective Studies ; Child ; *Reinfection/epidemiology/virology ; Male ; Female ; *SARS-CoV-2 ; Child, Preschool ; Infant ; Post-Acute COVID-19 Syndrome ; United States/epidemiology ; Young Adult ; },
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period.<br><br>METHODS: This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching.<br><br>FINDINGS: We identified 407&#x2009;300 (87&#xb7;5%) of 465&#x2009;717 eligible children and adolescents with a first infection episode and 58&#x2009;417 (12&#xb7;5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233&#x2009;842 (50&#xb7;2%) patients were male and 231&#x2009;875 (49&#xb7;8%) were female. The mean age was 8&#xb7;17 years (SD 6&#xb7;58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903&#xb7;7 (95% CI 780&#xb7;9-1026&#xb7;5) in the first infection group and 1883&#xb7;7 (1565&#xb7;1-2202&#xb7;3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2&#xb7;08 [1&#xb7;68-2&#xb7;59]) and a range of symptoms and conditions potentially related to PASC (RR range 1&#xb7;15-3&#xb7;60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms.<br><br>INTERPRETATION: Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies.<br><br>FUNDING: National Institutes of Health.},
}
@article {pmid41043208,
year = {2025},
author = {Li, M and Wisniewski, T and Silva, F and Hammam, S and Alvarez, Z and Bilici, N and Caceres, LC and De La Cruz, N and Engelson, C and Greenberg, J and Gummadi, B and Hunter, J and Hernandez, DI and Karimi, S and Links, J and Rodriguez, M and Vedvyas, A and Vinitsky, H and Yakubov, A and Ge, Y and Thawani, S and Balcer, L and Galetta, S and Frontera, JA},
title = {Functional and cognitive outcomes three years after COVID-19.},
journal = {Clinical neurology and neurosurgery},
volume = {258},
number = {},
pages = {109180},
doi = {10.1016/j.clineuro.2025.109180},
pmid = {41043208},
issn = {1872-6968},
mesh = {Humans ; *COVID-19/psychology/complications ; Female ; Male ; Middle Aged ; Aged ; Cohort Studies ; *Cognition/physiology ; Aged, 80 and over ; *Cognitive Dysfunction/etiology ; *Recovery of Function ; SARS-CoV-2 ; Longitudinal Studies ; },
abstract = {BACKGROUND: There is paucity of data on long-term functional and cognitive outcomes after COVID-19 compared to COVID-negative controls.<br><br>METHODS: We conducted an observational cohort study of patients &#x2265;&#x202f;1 year after COVID-19 compared to contemporaneous COVID-19 negative controls (SARS-CoV-2 nucleocapsid IgG negative with no history of COVID-19). Functional (modified Rankin Scale [mRS], Barthel Index), cognitive (telephone MoCA [t-MoCA]), and patient-reported neuropsychiatric symptoms were compared between groups using multivariable logistic regression analysis. In a subgroup of COVID-19 patients who were followed longitudinally, trajectories of recovery were assessed using the paired samples Sign test.<br><br>RESULTS: Of 145 participants, N&#x202f;=&#x202f;115 COVID-19 patients (median age 62, 51&#x202f;% female, 33&#x202f;% hospitalized for COVID-19, median 2.9 years from index infection), and N&#x202f;=&#x202f;30 non-COVID-19 controls (median age 75, 70&#x202f;% female) were enrolled. Neuropsychiatric symptoms were reported in 76&#x202f;% of COVID-19 patients versus 7&#x202f;% of controls (aOR 15.0, 95&#x202f;%CI 3.09-72.47, P&#x202f;<&#x202f;0.001). Abnormal mRS>&#x202f;0 occurred in 42&#x202f;% of COVID-19 patients compared to 11&#x202f;% of controls (P&#x202f;=&#x202f;0.002). However, this difference was not significant after adjusting for age, sex, COVID-19 hospitalization and history of mood disorder (aOR 2.10, 95&#x202f;%CI 0.52-8.51). Rates of abnormal t-MoCA&#x2264;&#x202f;18 (40&#x202f;% of COVID-19 versus 41&#x202f;% of controls, P&#x202f;=&#x202f;1.00) and Barthel scores<&#x202f;100 (19&#x202f;% of COVID-19 versus 14&#x202f;% in controls, P&#x202f;=&#x202f;0.785) were similar. Among N&#x202f;=&#x202f;26 COVID-19 patients with repeated measures, mRS significantly improved between 6-months to 3-years post-COVID (+1.3 points, p&#x202f;=&#x202f;0.004), while no changes were observed in t-MoCA or Barthel.<br><br>CONCLUSIONS: Three years after COVID-19, neuropsychiatric symptoms were significantly more frequent compared to controls, however no differences in functional or cognitive status were detected.},
}
@article {pmid41042487,
year = {2026},
author = {Joost, FEA and Rose, N and Kimmig, A and Ruhnke, T and Dröge, P and Freytag, A and Günster, C and Pletz, MW and Roesler, M and Reuken, PA and Schlattmann, P and Schmidt, KFR and Stallmach, A and Storch, J and Reinhart, K and Wedekind, L and Fleischmann-Struzek, C},
title = {Long-term outcomes after intensive care unit-treated COVID-19, influenza and respiratory sepsis in 2020 - a comparative, population-based cohort study.},
journal = {Infection},
volume = {54},
number = {1},
pages = {179-189},
pmid = {41042487},
issn = {1439-0973},
support = {01VSF21031//German Innovations Fund of the Federal Joint Committee/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/mortality/complications/therapy/epidemiology ; *Influenza, Human/complications/mortality/therapy/epidemiology ; Middle Aged ; Retrospective Studies ; Aged ; Intensive Care Units/statistics &amp; numerical data ; *Sepsis/mortality/therapy/epidemiology ; Germany/epidemiology ; Adult ; SARS-CoV-2 ; Aged, 80 and over ; Survivors ; Cohort Studies ; },
abstract = {BACKGROUND: Sepsis survivors are affected by a broad spectrum of long-term impairments, which overlap with Long-Covid and sequelae after influenza in their clinical presentation. However, we lack comparative assessments on the burden of long-term outcomes, particularly with patients being recruited from the same, contemporary patient population. Therefore we compared long-term outcomes after respiratory sepsis (RS), SARS-CoV-2-associated sepsis (SS) and influenza-associated sepsis (IS).<br><br>METHODS: Retrospective, population-based cohort study. We included patients&#x2009;>&#x2009;15&#xa0;years hospitalized with RS, SS and IS between 01/2020 and 12/2020 in Germany, who received intensive care unit treatment. We compared mortality, readmissions, prevalence of diagnoses in the cognitive, psychological or medical domain, and the number of impaired domains in the 12&#xa0;months post-discharge between the three survivor cohorts, adjusting for between-group differences in relevant covariates by inverse propensity score weighting based on generalized propensity scores.<br><br>RESULTS: Our study included 12,854 patients, of which 8,201 were RS, 3,964 SS and 689 IS survivors. RS survivors had a considerably higher risk for 12-month mortality compared to SS and IS survivors (relative risk, 1.77 [95% CI, 1.54-2.03]; P&#x2009;<&#x2009;0.001 and relative risk, 1.37 [95% CI, 1.14-1.65]; P&#x2009;=&#x2009;0.001, respectively). They were more often rehospitalized, affected by multiple domain impairments, cognitive decline and impairments related to the severity of acute disease, e.g. complications of the tracheostoma, compared to survivors after SS and IS. RS survivors had a lower risk for being affected by medical diagnoses compared to SS. Risks for psychological diagnoses did not differ between RS and the other survivor groups.<br><br>CONCLUSIONS: Although respiratory sepsis survivors seem to be affected by more severe long-term impairments, the overall burden of post-acute sequelae among all survivor groups is high. This warrants efforts to provide targeted aftercare for all survivor populations after life-threatening infections.},
}
@article {pmid41041184,
year = {2025},
author = {Anjum, A and Rauf, I and Mehvish, S and Parveen, S and Hussain, A},
title = {A cross-sectional study on long covid, cognition and neurasthenia-one year post covid.},
journal = {Journal of family medicine and primary care},
volume = {14},
number = {8},
pages = {3205-3210},
pmid = {41041184},
issn = {2249-4863},
abstract = {INTRODUCTION: The COVID-19 pandemic has led to long-term health effects in some patients, known as long COVID. This study aimed to delineate the symptoms of long COVID-19 and determine the presence of neurasthenia in patients one year after COVID-19 infection while excluding other potential causes of fatigue.<br><br>METHODS: A cross-sectional study was conducted on 512 RT-PCR-confirmed COVID-19 patients attending a follow-up clinic at least one year after infection. After excluding patients above 60 years, those with pre-existing psychiatric disorders, medical co-morbidities, and current psychiatric diagnoses, 87 patients were included in the final analysis. Patients were evaluated using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Fatigue Severity Scale (FSS), and memory scale of PGI-BBD. A semi-structured questionnaire assessed changes in activities of daily living.<br><br>RESULTS: Of the 87 patients, 43 (49.4%) fulfilled the ICD-10 criteria for neurasthenia. Fatigue interfering with daily activities was reported by 41.3% of patients, with a mean FSS score of 6.1 in those with neurasthenia. Other symptoms included muscular aches (35.6%), tension headaches (27.5%), and weakness (31%). Cognitive difficulties, specifically problems with attention and concentration, were observed in 8% of patients. The severity of the initial COVID-19 infection did not correlate with the risk of developing neurasthenia.<br><br>CONCLUSION: Long COVID symptoms, particularly those resembling neurasthenia, persist in a significant proportion of patients one year after infection. The syndrome of long COVID shows similarities to the ICD-10 diagnosis of neurasthenia, suggesting a potential link between post-COVID symptoms and chronic low-grade inflammation. These findings highlight the need for recognition and management of long-term COVID-19 effects in public health policies.},
}
@article {pmid41038893,
year = {2025},
author = {da Silva Almeida, I and de Jesus Ferreira, LG and Cipriano, G and Costa, RR and Vaz, MA and Babault, N and de Cássia Marqueti, R and Durigan, JLQ},
title = {Persistent neuromuscular disorders associated with changes in tibialis anterior and gastrocnemius lateralis muscle architecture in long-covid: an observational longitudinal study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34375},
pmid = {41038893},
issn = {2045-2322},
support = {001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 00193.00000773/2021-72//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193.00001222/2021-26//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 00193-00001261/2021-23//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal/ ; 141130/2023-7//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 131422/2023-5//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309435/2020-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 310269/2021-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 00193.00000859/2021-3//Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal, Brazil/ ; },
mesh = {Humans ; Male ; *Muscle, Skeletal/diagnostic imaging/pathology/physiopathology ; Female ; *COVID-19/complications/physiopathology ; Longitudinal Studies ; Middle Aged ; Adult ; *Neuromuscular Diseases/etiology/physiopathology/pathology/diagnostic imaging ; SARS-CoV-2 ; Ultrasonography ; },
abstract = {Long COVID-19 causes complications, affecting quality of life and work capacity. However, its long-term impact on lower limb neuromuscular function remains unclear. To evaluate neuromuscular electrophysiological disorders (NEDs) and muscle architecture of the tibialis anterior (TA) and triceps surae (TS) in individuals with moderate or severe COVID-19 compared to control group over 12 months. Seventy participants were divided into moderate-COVID (n = 22), severe-COVID (n = 18), and control (n = 30) groups. COVID groups underwent four assessments over one year. NEDs in the TA and gastrocnemius lateralis (GL) were assessed via stimulus electrodiagnostic testing, while TA and TS muscle architecture was evaluated using ultrasound. Participants with severe-COVID exhibited significantly higher chronaxie (p < 0.001) in the TA at the first assessment, NEDs were observed in 55.55%, 33.33%, and 16.66% of participants across the first three assessments. GL showed 5.55% prevalence of NEDs. Echogenicity increased in TA and GL muscles in the severe-COVID group (p < 0.001). An association was found between TA chronaxie and echogenicity in the COVID groups during the short-term assessment (p < 0.001). Severe COVID-19 is associated with higher prevalence of NEDs in the TA muscle and persistent echogenicity increases, suggesting polyneuromyopathy in the TA and widespread echogenicity abnormalities in long COVID patients.},
}
@article {pmid41038267,
year = {2025},
author = {Thomas, D and Yang, PC and Wu, JC and Sayed, N},
title = {Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.},
journal = {Journal of molecular and cellular cardiology},
volume = {209},
number = {},
pages = {37-50},
pmid = {41038267},
issn = {1095-8584},
support = {R01 HL161002/HL/NHLBI NIH HHS/United States ; R01 HL130020/HL/NHLBI NIH HHS/United States ; R01 HL176822/HL/NHLBI NIH HHS/United States ; R01 HL146690/HL/NHLBI NIH HHS/United States ; K01 HL135455/HL/NHLBI NIH HHS/United States ; R35 HL150698/HL/NHLBI NIH HHS/United States ; K99 HL163443/HL/NHLBI NIH HHS/United States ; R01 HL145676/HL/NHLBI NIH HHS/United States ; R01 HL158641/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/complications/virology/pathology ; *Cardiovascular Diseases/etiology/virology/physiopathology/pathology ; *SARS-CoV-2 ; Animals ; Induced Pluripotent Stem Cells ; Post-Acute COVID-19 Syndrome ; },
abstract = {The COVID-19 pandemic has revealed that the impact of SARS-CoV-2 infection extends well beyond the acute phase, with long-term sequelae affecting multiple organ systems, most notably, the cardiovascular system. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms such as fatigue, dyspnea, chest pain, and palpitations, which can last for months or even years after initial recovery. Increasing evidence implicates immune dysregulation, endothelial dysfunction, persistent viral antigens, and coagulopathy as central drivers of cardiovascular complications. Mechanistic studies demonstrate that direct viral infection of cardiac and vascular cells, along with autoantibody formation and cytokine-mediated injury, contribute to myocardial inflammation, fibrosis, and arrhythmias. Sex-based immunological differences and underlying comorbidities further influence individual susceptibility and disease trajectory. Large-scale epidemiological studies have confirmed significantly increased risks of pericarditis, cardiomyopathy, dysrhythmias, and heart failure among COVID-19 survivors. In parallel, the emergence of advanced preclinical platforms, including patient-derived induced pluripotent stem cell (iPSC)-based cardiac organoids, engineered heart tissues, and organ-on-a-chip systems has enabled mechanistic dissection of Long COVID pathophysiology. These human-relevant models, when integrated with clinical datasets and artificial intelligence (AI)-driven analytics, offer powerful tools for biomarker discovery, risk stratification, and precision therapeutic development. This review synthesizes the current understanding of cardiovascular involvement in Long COVID, highlights key mechanistic insights from both clinical and preclinical studies, and outlines future directions for diagnostic and therapeutic innovation.},
}
@article {pmid41037811,
year = {2026},
author = {Metz, TD and Reeder, HT and Clifton, RG and Flaherman, V and Aragon, LV and Baucom, LC and Beamon, CJ and Braverman, A and Brown, J and Carmilani, M and Cao, T and Chang, A and Costantine, MM and Dionne, JA and Gibson, KS and Gross, RS and Guerreros, E and Habli, M and Hess, R and Hillier, L and Hodder, S and Hoffman, MC and Hoffman, MK and Huang, W and Hughes, BL and Jia, X and Kale, M and Katz, SD and Laleau, V and Mendez-Figueroa, H and McComsey, GA and Ofotokun, I and Okumura, MJ and Pacheco, LD and Palatnik, A and Palomares, KTS and Parry, S and Pettker, CM and Plunkett, BA and Poppas, A and Ramsey, P and Reddy, UM and Rouse, DJ and Saade, GR and Sandoval, GJ and Sciurba, F and Simhan, HN and Skupski, DW and Sowles, A and Thorp, JM and Tita, ATN and Wiegand, S and Weiner, SJ and Yee, LM and Horwitz, LI and Foulkes, AS and Jacoby, VL and , },
title = {Long COVID After Acquisition of the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) During Pregnancy Compared With Outside of Pregnancy.},
journal = {Obstetrics and gynecology},
volume = {147},
number = {3},
pages = {404-414},
pmid = {41037811},
issn = {1873-233X},
support = {OT2HL161841/HL/NHLBI NIH HHS/United States ; UG1 HD027915/HD/NICHD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Female ; Pregnancy ; *COVID-19/epidemiology/virology ; Adult ; *Pregnancy Complications, Infectious/epidemiology/virology ; *SARS-CoV-2 ; Young Adult ; Adolescent ; Middle Aged ; United States/epidemiology ; Cohort Studies ; },
abstract = {OBJECTIVE: To evaluate whether the risk of long COVID among individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy differs from that of individuals who were not pregnant at time of virus acquisition.<br><br>METHODS: We conducted a multicenter observational cohort study at 79 NIH RECOVER (Researching COVID to Enhance Recovery) sites. Individuals assigned female at birth aged 18-45 years with an index (first) SARS-CoV-2 infection on or after December 1, 2021, were included. The exposure was pregnancy (any gestational age) at the time of index SARS-CoV-2 infection. The primary outcome was long COVID 6 months after index infection , defined as RECOVER-Adult Long COVID Research Index score 11 or higher based on a detailed symptom survey. To account for confounding and differential selection between participants who were pregnant and not pregnant at infection, propensity score-matching methods were used to balance the groups on variables potentially associated with both pregnancy status and long COVID.<br><br>RESULTS: Overall 2,423 participants were included; 580 (23.9%) were pregnant at index SARS-CoV-2 infection. The median age at infection was 33 years (interquartile range 28-38 years), and 2,131 of participants (90.0%) with known vaccination status were vaccinated. After propensity score matching, the adjusted long COVID prevalence estimates 6 months after index infection were 10.2% (95% CI, 6.2-14.3%) among those pregnant at infection and 10.6% (95% CI, 8.8-12.4%) among those not pregnant at infection. Pregnancy was not associated with a difference in adjusted risk of long COVID (adjusted risk ratio 0.96, 95% CI, 0.63-1.48).<br><br>CONCLUSION: Acquisition of SARS-CoV-2 during pregnancy was not associated with a differential risk of long COVID at 6 months compared with similar-aged individuals who acquired SARS-CoV-2 outside of pregnancy.},
}
@article {pmid41036702,
year = {2025},
author = {Thierry, AR and Usher, T and Sanchez, C and Turner, S and Venter, C and Pastor, B and Waters, M and Thompson, A and Mirandola, A and Pisareva, E and Prevostel, C and Laubscher, GJ and Kell, DB and Pretorius, E},
title = {Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients.},
journal = {Journal of medical virology},
volume = {97},
number = {10},
pages = {e70613},
pmid = {41036702},
issn = {1096-9071},
support = {//The study was partially supported by SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553 (ART); South African National Research Foundation (142142); (EP); and the South African Medical Research Foundation (EP), the Novo Nordisk Foundation grant NNF20CC0035580 (DBK) and the Balvi Foundation grant 18 (DBK)./ ; },
mesh = {Humans ; *Extracellular Traps/metabolism ; *COVID-19/blood/complications/pathology ; Male ; Middle Aged ; Female ; Leukocyte Elastase/blood ; *Neutrophils/metabolism ; Biomarkers/blood ; Aged ; Fibrin/metabolism ; SARS-CoV-2 ; Adult ; },
abstract = {The persistence of vasculo-thrombotic complications has been put forward as a possible contributing factor in the Long COVID (LC) syndrome. Given the recently reported separate demonstration of the association of LC with elevated levels of heterogenous fibrin(ogen) amyloidogenic particles (microclots) and with those neutrophil extracellular traps (NETs), markers that are linked to thromboinflammation, this study considers the association of microclots with NETs. The results show that NETs markers (Myeloperoxydase, Neutrophil Elastase, and circulating DNA) are quantitatively and structurally associated with the size and number of microclots in patients with LC. These markers showed a strong diagnostic performance, both independently and when combined. Our study revealed that NETs may be a component of circulating microclots. We suggest that higher NETs formation might promote the stabilization of microclots in the circulation, potentially leading to deleterious effects which contribute causally to the LC syndrome.},
}
@article {pmid41036177,
year = {2025},
author = {Fujimoto, Y and Abe, H and Eiro, T and Tsugawa, S and Tanaka, M and Hatano, M and Nakajima, W and Ichijo, S and Arisawa, T and Takada, Y and Kimura, K and Sano, A and Hirahata, K and Sasaki, N and Kimura, Y and Takahashi, T},
title = {Systemic increase of AMPA receptors associated with cognitive impairment of long COVID.},
journal = {Brain communications},
volume = {7},
number = {5},
pages = {fcaf337},
pmid = {41036177},
issn = {2632-1297},
abstract = {Long COVID primarily presents with persistent cognitive impairment (Cog-LC), imposing a substantial and lasting global burden. Even after the pandemic, there remains a critical global need for diagnostic and therapeutic strategies targeting Cog-LC. Nevertheless, the underlying neural mechanisms remain poorly understood. Given the central role of synapses in brain function, investigation of synaptic molecular changes may provide vital insights into Cog-LC pathophysiology. In this study, we used [[11]C]K-2 PET to characterize the density of AMPA receptors (AMPARs) on the post-synaptic cell surface, which are crucial synaptic components in brain signalling. Statistical parametrical mapping was used to spatially normalize and apply independent t-test for a voxel-based comparison. We selected patients with Cog-LC (n = 30) based on Repeatable Battery for the Assessment of Neuropsychological Status assessed persistent cognitive impairment and healthy controls (n = 80) with no diagnosed neuropsychiatric disorders. The primary objective was to compare [[11]C]K-2 standardized uptake value ratio with white matter (SUVRWM) as a reference region between patients with Cog-LC and healthy controls, and to define the regional extent of differences. The secondary objective was to examine associations between [[11]C]K-2 SUVRWM and plasma concentrations of cytokines or chemokines. As an exploratory objective, we tested whether [[11]C]K-2 PET data could distinguish Cog-LC from healthy controls using a partial least squares based classification algorithm. A voxel-based comparison (P < 0.05, T > 1.66, one-tailed, false discovery rate control) and a volume of interests analysis (P < 0.05, Bonferroni multiple comparison) demonstrated that increased index of AMPAR density in large parts of the brains of patients with Cog-LC compared with that in healthy controls. A voxel-based correlation analysis also showed the brain regions where [[11]C]K-2 SUVRWM correlated positively with plasma TNFSF12 and negatively with plasma CCL2 concentrations. A partial least squares model trained on the index of AMPAR density data demonstrated high diagnostic accuracy, achieving 100% sensitivity and 91.2% specificity. [[11]C]K-2 PET signal represents the index of AMPAR density on the post-synaptic neural cell surface, not on the glial cell surface. A systemic increase in synaptic AMPARs across the brain may drive abnormal information processing in Cog-LC and, through excessive excitatory signalling, pose a risk of excitotoxic neuronal damage. We derived the hypothesis that [[11]C]K-2 PET would be helpful in establishing a diagnostic framework for Cog-LC and that antagonists for cell surface AMPARs, such as perampanel, would be a potential therapeutic target. These hypotheses should be investigated in future large-scale clinical studies.},
}
@article {pmid41035536,
year = {2025},
author = {Daher, J and Koberssy, Z and Durieux, JC and Atieh, O and Baissary, J and Abboud, M and McComsey, GA},
title = {Cognitive Function 1 Year After COVID Infection.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf583},
pmid = {41035536},
issn = {2328-8957},
support = {UM1 TR004528/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: While emerging evidence suggests a potential link between COVID-19 and cognitive impairment, there is a lack of prospective longitudinal research that objectively assesses cognitive outcomes after SARS-CoV-2 infection. This study aims to evaluate changes in cognitive function following COVID-19 in a group of individuals with baseline pre-infectious cognitive assessments.<br><br>METHODS: In this cohort study, cognitive function was objectively measured using the computerized Cognivue Clarity&#xae; device. All participants who had available Cognivue&#xae; testing were followed with a second Cognivue&#xae; assessment &#x223c;1 year later. Based on whether they contracted COVID-19 during this period, participants were categorized into 2 groups according to COVID status.<br><br>RESULTS: We enrolled 110 participants with a median age of 45 years, 35% females and 46% white; 55 (50%) participants experienced a documented COVID-19 infection during the follow-up period (COVID + group), and the rest remained free of COVID infection (COVID- group). COVID- and COVID + groups were balanced for demographics and duration of follow-up. In the COVID + group, only memory scores changed during follow-up (+3.9; P = .03). The COVID- group showed improvements in the overall Cognivue&#xae; score (+2; P = .03), as well as in visuospatial (+1.9; P = .04), executive function (+2.2; P = .02), and naming language (+2.2; P = .01) scores. No statistically significant differences were observed in the overall cognitive score or its subdomains between the 2 groups.<br><br>CONCLUSIONS: In a 45-year-old average population, no decrease in cognitive function was observed 1 year after COVID-19 infection.},
}
@article {pmid41034315,
year = {2025},
author = {Roy, S and Malik, A and Singh, A and Ray, S},
title = {Long term health related quality of life among individuals after COVID 19 recovery in a multicentric community based study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34225},
pmid = {41034315},
issn = {2045-2322},
support = {OR/3/11/2021-ECD-II//Department of Health Research, Ministry of Health and Family Welfare, Government of India/ ; },
mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology/psychology ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; SARS-CoV-2/isolation &amp; purification ; India/epidemiology ; Young Adult ; Surveys and Questionnaires ; Health Status ; },
abstract = {The COVID-19 pandemic has had a profound and far-reaching impact on global health, resulting in significant morbidity and mortality across populations. Long term post COVID-19 conditions can include neurological symptoms, chronic fatigue, and mental health disorders, which collectively contribute to a deterioration in health-related quality of life. This study aims assess long-term HRQoL using EuroQol (EQ 5D 5L) among COVID-19 patients in community settings. This study conducted a multicentric, community-based cross-sectional design to assess the long-term HRQoL among patients who have recovered from COVID-19. The study included participants aged above 18 years from two cities Delhi and Bhubaneswar. Descriptive statistics of categorical variables were presented in frequency and percentage, while continuous variables were presented in mean ± SD. The censored regression analysis has been performed by reporting beta coefficients and significance by (p < 0.05). The EQ-5D-5L index scores indicated a mean of 0.89 (95% CI 0.87, 0.91) for Delhi, compared to a lower mean score of 0.66 (95% CI 0.62, 0.71) for Bhubaneswar. Age was negatively correlated with health states, showing a crude coefficient of - 0.003 (95% CI - 0.005, 0.001) with a significant p value of 0.002, although the adjusted coefficient was - 0.002 (95% CI - 0.005, 0.001), indicating a loss of significance when controlling for other factors. The emphasizes the health-related quality of life of the COVID-19 recovered patients and challenges in their daily living. The study descriptively highlighting the quality-of-life and in association with age, educational status, marital status, health insurance availability, and treatment setting.},
}
@article {pmid41033506,
year = {2025},
author = {Greene, C},
title = {The broken barrier: neurovascular insights into long COVID.},
journal = {Brain, behavior, and immunity},
volume = {130},
number = {},
pages = {106126},
doi = {10.1016/j.bbi.2025.106126},
pmid = {41033506},
issn = {1090-2139},
}
@article {pmid41033183,
year = {2025},
author = {Shimada, T and Tanabe, N and Chubachi, S and Asakura, T and Namkoong, H and Tanaka, H and Azekawa, S and Otake, S and Nakagawara, K and Fukushima, T and Watase, M and Maetani, T and Shiraishi, Y and Terai, H and Sasaki, M and Ueda, S and Kato, Y and Harada, N and Suzuki, S and Yoshida, S and Tateno, H and Yamada, Y and Jinzaki, M and Hirai, T and Okada, Y and Koike, R and Ishii, M and Kimura, A and Imoto, S and Miyano, S and Ogawa, S and Kanai, T and Fukunaga, K},
title = {Extent of pulmonary involvement on admission predicts long-term pulmonary and muscular sequelae of COVID-19: A longitudinal computed tomography study.},
journal = {Respiratory investigation},
volume = {63},
number = {6},
pages = {1215-1220},
doi = {10.1016/j.resinv.2025.09.014},
pmid = {41033183},
issn = {2212-5353},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Tomography, X-Ray Computed ; Male ; Female ; *Lung/diagnostic imaging/pathology ; Middle Aged ; Aged ; Longitudinal Studies ; Severity of Illness Index ; Time Factors ; Adipose Tissue/diagnostic imaging ; Muscular Atrophy/diagnostic imaging/etiology ; Bone Density ; Patient Admission ; Adult ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Studies on the association between chest computed tomography (CT) findings of extensive pulmonary involvement and long-term pulmonary and extrapulmonary coronavirus disease 2019 (COVID-19) sequelae are lacking. This study aimed to investigate the relationship between the severity of pneumonia on admission and residual pulmonary and extrapulmonary complications at three months post-hospitalization.<br><br>METHODS: Using data from the Japan COVID-19 Task Force database, we conducted quantitative analysis of CT scans of 164 patients obtained at admission and three months later. The parameters included pneumonia volume, total lung volume, and area and density of the pectoralis muscle (PM), subcutaneous and epicardial adipose tissue, and vertebral bone density.<br><br>RESULTS: Patients with extensive pneumonia on admission had high residual pneumonia volumes, reduced lung volumes, and decreased area and density of PM at three months. No significant differences were observed in the adipose tissue or bone parameters. The severity of pneumonia at admission was independently associated with PM atrophy.<br><br>CONCLUSIONS: CT-based quantification of pneumonia extent during the acute phase of COVID-19 may be useful in predicting long-term pulmonary sequelae and muscle wasting. This approach may allow the objective evaluation of Long COVID and facilitate the identification of potential therapeutic targets.},
}
@article {pmid41031103,
year = {2025},
author = {Dalton, AF and Baca, S and Raykin, J and Gregory, CO and Boehmer, T and Koumans, EH and Patel, PR and Patel, P and Saydah, S},
title = {Risk of Post-COVID-19 Conditions Among Adolescents and Adults Who Received Nirmatrelvir-Ritonavir for Acute COVID-19: A Retrospective Cohort Study.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf567},
pmid = {41031103},
issn = {2328-8957},
abstract = {BACKGROUND: Post-COVID-19 Conditions (PCC) potentially affect millions of people, but it is unclear whether treating acute COVID-19 with nirmatrelvir-ritonavir may reduce the risk of PCC.<br><br>METHODS: This is a retrospective cohort study using real-world, closed claims data to assess the relationship between nirmatrelvir-ritonavir and PCC by age group (12-17, 18-49, 50-64, &#x2265;65 years). Eligible patients had a COVID-19 index date (positive laboratory test, ICD-10 diagnosis code, or nirmatrelvir-ritonavir prescription) from 1 April to 31 August 2022, in the outpatient, telehealth, or emergency department setting, and had a higher risk of severe COVID-19 based on age (&#x2265;50 years) or underlying risk factors. Treated patients (ie, received a nirmatrelvir-ritonavir prescription within &#xb1;5 days of index date) were matched 1:2 on age, sex, month of index date, and HHS region with untreated patients. PCC was defined by the presence of &#x2265;1 of 45 new-onset symptoms or conditions recorded &#x2265;60 days after index date.<br><br>RESULTS: Of the treated patients, 291 433 were matched to 582 866 untreated patients. Treatment with nirmatrelvir-ritonavir reduced PCC risk in adults 50-64 years (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [CI] 0.92-0.95) and &#x2265;65 years (aHR 0.88, 95% CI 0.87-0.90). Treatment had minimal effect among high-risk adults 18-49 years (aHR 0.98, 95% CI 0.97-0.99) and no effect among high-risk adolescents 12-17 years (aHR 1.06, 95% CI 0.66-1.13).<br><br>CONCLUSIONS: Results using real-world data suggest a protective relationship between nirmatrelvir-ritonavir during acute illness and PCC risk among older adults, but not among adolescents. Consideration may be given to outpatient treatment of mild to moderate COVID-19 with nirmatrelvir-ritonavir to reduce the risk of severe disease and PCC.},
}
@article {pmid41030634,
year = {2025},
author = {Johnson, BL},
title = {"In-Flu-Enza and Out-Flew Hair:" Post-Epidemic Health and the Importance of the History of Epidemics.},
journal = {The Yale journal of biology and medicine},
volume = {98},
number = {3},
pages = {341-348},
pmid = {41030634},
issn = {1551-4056},
mesh = {Humans ; *COVID-19/epidemiology/history ; History, 20th Century ; *Influenza, Human/epidemiology/history ; SARS-CoV-2 ; *Epidemics/history ; Pandemics/history ; History, 21st Century ; Influenza Pandemic, 1918-1919/history ; },
abstract = {When COVID-19 survivors reported ongoing symptoms or new health concerns following their infections in 2020 and early 2021, many medical practitioners and health agencies questioned the connection between novel viruses and long-term health impacts. Medical historians studying epidemics understand the connection between viral infection and health complications emerging immediately or years or decades later. In this essay, I explore the similarities between the medical fallout of the 1918 influenza and COVID-19 pandemics. Despite the differences between the viruses, these novel strains produced similar medium- and long-term health difficulties, including cardiovascular dysfunction and crushing fatigue. As I demonstrate, a significant difference between these two pandemics is in the response by medical practitioners. Following influenza, practitioners expected new and worsening health issues and took their patients' complaints seriously, offering support through food delivery, convalescent care, specialist oversight, and in-home nursing. Early in the COVID-19 pandemic, many practitioners characterized ongoing or new symptoms as anxiety. Patients led efforts to recognize Long COVID as an authentic medical condition, and today, physicians around the country refer their patients to Long COVID clinics. The value of medical history is apparent in this comparison-if practitioners understand how historical epidemics impacted various populations, they expect that in the epidemic aftermath or the period following an acute epidemic crisis, not all patients get well. Including the history of epidemics in public health education, continuing education programming, and even medical school curricula can resist epidemic erasure and empower medical practitioners to expect the unexpected.},
}
@article {pmid41029812,
year = {2025},
author = {Su, S and Jiang, Z and Shi, L and Liu, X and Zhang, Z and Mei, H and Gao, N and Wu, S and Li, M and Zhang, X and Zhang, A and Tang, C and Zheng, Y and Zhao, Y and Zeng, N and Ni, S and Yan, W and Yuan, K and Sun, Y and Hong, Y and Lu, Y and Shi, J and Bao, Y and Li, X and Lu, L},
title = {Physical, cognitive, and mental health impacts of Omicron reinfection in patients with original SARS-CoV-2 infection: a community-based observational study.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {526},
pmid = {41029812},
issn = {1741-7015},
support = {2021ZD0200700//the National Programs for Brain Science and Brain-like Intelligence Technology of China (STI2030-Major Projects)/ ; 82171514//the National Natural Science Foundation of China/ ; 81761128036//the National Natural Science Foundation of China/ ; 2024YFC2707801//National Key Research and Development Program of China Stem Cell and Translational Research/ ; BMU2022DJXK007//the Fundamental Research Funds for the Central Universities (Peking University Medicine Fund for world's leading discipline or discipline cluster development)/ ; 2021YFC0863700//National Key Research and Development Program of China/ ; 2021ZD0200800//the National Programs for Brain Science and Brain-like Intelligence Technology of China (STI2030-Major Project)/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology ; *COVID-19/complications/epidemiology/psychology/virology ; *Mental Health ; *Reinfection/complications/epidemiology/psychology/virology ; *SARS-CoV-2 ; },
abstract = {BACKGROUND: Epidemiological and clinical evidence suggests that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reinfection is a complication in a proportion of patients reporting ongoing health issues. However, most studies in the field of SARS-CoV-2 reinfection have focused only on self-reported symptoms and lacked long-term objective measurements. This study aimed to estimate the pattern of chronic symptoms of Omicron reinfection in patients with original SARS-CoV-2 infection by comprehensively assessments 3 years after recovery.<br><br>METHODS: This community-based observational study was conducted in Wuhan, China, between January and April in 2023. All participants were recruited from community and invited to participate the interview and examination in a hospital. The subjective multi-system symptoms were self-reported. The objective radiological features and laboratory data were assessed by measuring blood inflammation and performing chest computed tomography (CT) and pulse oxygen saturation.<br><br>RESULTS: Among 1438 individuals who participated in the study, 144 were infected with the original variant only in 2020, 980 were Omicron-infected in 2023, 215 were reinfected both in 2020 and 2023, and 99 were never infected. Compared with the non-infection group, the reinfection (odds ratio (OR), 5.15 [95% confidence intervals (CIs), 2.96-8.96]) group was associated with the highest risk of any of chronic physical symptoms, followed by the Omicron infection (3.45 [2.19-5.44]) and original variant infection (2.90 [1.63-5.15]) groups. Compared with the non-infection group, the reinfection (4.05 [2.30-7.14]), Omicron infection (3.72 [2.26-6.11]), and original variant infection (2.71 [1.48-4.95]) groups were associated with an increased risk of any of chronic mental symptoms. Moreover, of all groups, the reinfection group reported the highest seropositivity rate for C-reactive protein, and the highest prevalence rates of ground glass opacities on chest CT and hypoxaemia.<br><br>CONCLUSIONS: Our results suggest that reinfection may be a risk factor for long COVID conditions. These findings provide information for the clinical management and healthcare services of long COVID and SARS-CoV-2 reinfection and highlight the importance taking necessary action to prepare for a future pandemic. The long-term follow-up will be needed to verify the impact of different SARS-CoV-2 infection status on long COVID in the future.},
}
@article {pmid41029414,
year = {2025},
author = {Dempsey, B and Blake, HA and Madan, I and Stevelink, SAM and Greenberg, N and Raine, R and Rafferty, AM and Bhundia, R and Wessely, S and Lamb, D},
title = {COVID-19-related sickness absence among 4,721 NHS staff in England and its relation with long COVID symptoms: findings from NHS CHECK.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {1243},
pmid = {41029414},
issn = {1472-6963},
support = {CF/01/22//Colt Foundation/ ; M952//Rosetrees Trust/ ; MR/V034405/1/MRC_/Medical Research Council/United Kingdom ; ES/V009931/1//Economic and Social Research Council/ ; ISSF3/ H17RCO/C3//UCL/Wellcome/ ; },
abstract = {BACKGROUND: Long COVID (LC) occurs when COVID-19 symptoms continue for 12 + weeks after the onset of infection. LC may have several impacts, including sickness absence. This study explored number of days off work due to COVID-19 infection among healthcare workers (HCWs) and predictors of long-term sickness absence (i.e., 4 + consecutive weeks off work).<br><br>METHODS: Data were from the NHS CHECK survey and included 4,721 HCWs (19.6% of the cohort) who reported COVID-19-related symptoms and sickness absence at two follow-up periods, approximately 12 and 32 months post-baseline (baseline collected between April 2020 and January 2021). We conducted descriptive analysis to explore COVID-19-related sickness absence at both timepoints and to examine differences depending on whether HCWs self-reported symptoms consistent with LC or an LC diagnosis. We used multi-level logistic regression modelling to explore baseline predictors for reporting long-term sickness absence at follow-up among HCWs who reported LC symptoms.<br><br>RESULTS: At 12 months, 89.5% of HCWs attributed sickness absence to a COVID-19 infection, while 84.6% reported the same at 32 months. Median self-reported days off work at both timepoints were higher among HCWs who self-reported LC symptoms (12mo&#x2009;=&#x2009;14 days (IQR&#x2009;=&#x2009;10&#x2013;30), 32mo&#x2009;=&#x2009;7 days (IQR&#x2009;=&#x2009;4&#x2013;14)) compared with HCWs who did not (12mo&#x2009;=&#x2009;9.5 days (IQR&#x2009;=&#x2009;3.5&#x2013;14), 32mo&#x2009;=&#x2009;5 days (IQR&#x2009;=&#x2009;2&#x2013;7)). A similar finding was observed for HCWs who reported a formal diagnosis of LC compared with those who did not. There was a noticeable reduction in COVID-19-related sickness absence between our 12 and 32 month follow-up surveys across all groups. Among HCWs who self-reported LC symptoms, predictors for reporting long-term sickness absence at both timepoints included having a pre-existing respiratory illness and being aged 41&#x2013;50 years.<br><br>CONCLUSIONS: We found that reporting LC symptoms or having an LC diagnosis were associated with greater sickness absence among HCWs. The cause of the reduction in reported sickness absence between the timepoints is unclear, though it is most likely due to natural recovery from COVID-19, greater support available to staff with LC or the withdrawal of a special COVID-19 sickness absence payment in 2022. The need to support workers with LC to return and remain in work is still present.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-025-13442-w.},
}
@article {pmid41029357,
year = {2025},
author = {Dhariwal, R and Thakkar, K and Vaghela, K and Jain, M},
title = {Evaluating post-acute COVID-19 sequelae in younger population using symptom burden questionnaire (SQL).},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3195},
pmid = {41029357},
issn = {1471-2458},
mesh = {Humans ; Female ; *COVID-19/complications/epidemiology/psychology ; Cross-Sectional Studies ; Male ; Young Adult ; Adult ; Adolescent ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Anxiety/epidemiology ; Depression/epidemiology ; Prevalence ; Symptom Burden ; },
abstract = {The COVID-19 pandemic, declared by the World Health Organization on March 11, 2020, has led to over 650 million infections globally and a significant burden of long-term health issues, termed post-COVID-19 condition (PCC) or long COVID or post-acute sequelae of COVID-19 (PASC). This cross-sectional study assesses the prevalence and distribution of persistent symptoms among individuals aged 18-25 years using the Symptom Burden Questionnaire™ for Long COVID (SBQ™-LC), which evaluates 123 symptoms across 17 health domains. Our hypothesis interprets that the pandemic has laid mental health challenges among younger populations, evidenced by increased rates of depression and anxiety. Data from participants revealed high rates of mental health issues, sleep disturbances, and cognitive dysfunctions, even among those with mild or asymptomatic infections. Notably, female participants reported higher symptom severity across most domains. This research underscores the necessity for targeted assessments of post-acute sequelae in young adults to enhance understanding and management of long COVID-related health issues.},
}
@article {pmid41029289,
year = {2025},
author = {Lo, YP and Chiang, SL and Song, CY and Tzeng, WC and Chang, CC and Lin, CH},
title = {Associations between moderate-to-high physical activity levels and long COVID symptoms, heart rate recovery, cardiorespiratory fitness, sleep quality, and quality of life in patients with long COVID: a cross-sectional study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3204},
pmid = {41029289},
issn = {1471-2458},
support = {TSGH-D-112176//Tri-Service General Hospital/ ; TSGH-E-112249//Tri-Service General Hospital/ ; MND MAB-D-113085//Ministry of National Defense-Medical Affairs Bureau/ ; },
mesh = {Humans ; Cross-Sectional Studies ; *Quality of Life ; Male ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; *Heart Rate/physiology ; *Cardiorespiratory Fitness/physiology ; *Exercise/physiology ; *Sleep Quality ; Taiwan ; Adult ; Surveys and Questionnaires ; Aged ; },
abstract = {BACKGROUND: Moderate-to-high physical activity (PA) levels have been shown to mitigate health complications, improve cardiovascular health, and enhance patient-reported outcomes, such as sleep quality and quality of life (QoL), among patients with chronic diseases. However, little is known about the associations between moderate-to-high PA levels and long COVID symptoms, heart rate recovery, cardiorespiratory fitness, sleep quality, and QoL among patients with long COVID. This study aimed to examine whether moderate-to-high PA levels are associated with more favorable outcomes in terms of long COVID symptoms, heart rate recovery, cardiorespiratory fitness, and QoL, compared to those with low PA levels.<br><br>METHODS: A cross-sectional study was conducted to recruit patients with long COVID (n&#x2009;=&#x2009;219) from an integrated outpatient clinic for post-COVID-19 at a medical center in northern Taiwan. Eligible participants were categorized into moderate-to-high and low PA groups. PA levels, sleep quality, and QoL were assessed using the International Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, and World Health Organization Quality of Life Questionnaire-short form, respectively. Cardiorespiratory fitness and heart rate recovery were evaluated using cycle ergometer-based graded exercise tests. Multivariate linear and logistic regression models were used to evaluate the associations between PA levels, long COVID symptoms, heart rate recovery, sleep quality, and QoL.<br><br>RESULTS: Participants with a mean age of 48.7 years had a mean duration of post-COVID-19 of 12.3 weeks. Patients with moderate-to-high PA levels had a borderline lower risk of shortness of breath (OR&#x2009;=&#x2009;0.44, p&#x2009;=&#x2009;0.065), significantly greater VO&#x2082; peak (B&#x2009;=&#x2009;4.68, p&#x2009;<&#x2009;0.001) and 2-minute heart rate recovery (B&#x2009;=&#x2009;3.79, p&#x2009;=&#x2009;0.049), better sleep quality (B = -1.68, p&#x2009;=&#x2009;0.007), and higher scores in the physical (B&#x2009;=&#x2009;0.99, p&#x2009;=&#x2009;0.023) and psychological (B&#x2009;=&#x2009;1.11, p&#x2009;=&#x2009;0.030) domains of QoL, compared to those with lower PA levels.<br><br>CONCLUSIONS: Maintaining moderate-to-high PA levels among patients with long COVID may be associated with reduced symptom distress, greater cardiorespiratory fitness and heart rate recovery, and better sleep quality, which are in turn linked to better QoL.<br><br>CLINICAL TRIAL NUMBER: not applicable.},
}
@article {pmid41028062,
year = {2025},
author = {Mezache, L and Soltisz, A and Tili, E and Nuovo, GJ and Veeraraghavan, R},
title = {SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33991},
pmid = {41028062},
issn = {2045-2322},
support = {R01 HL148736/HL/NHLBI NIH HHS/United States ; R01 HL165751/HL/NHLBI NIH HHS/United States ; R01HL165751/HL/NHLBI NIH HHS/United States ; R01HL148736/HL/NHLBI NIH HHS/United States ; },
mesh = {*Spike Glycoprotein, Coronavirus/metabolism ; Animals ; *COVID-19/complications/virology/pathology ; *SARS-CoV-2/metabolism ; Connexin 43/metabolism ; Mice ; NAV1.5 Voltage-Gated Sodium Channel/metabolism ; Humans ; *Inflammation/virology ; *Arrhythmias, Cardiac/etiology/virology ; *Atrial Fibrillation/etiology/virology/pathology ; Male ; Mice, Inbred C57BL ; Angiotensin-Converting Enzyme 2/metabolism ; },
abstract = {Coronavirus disease 2019 (COVID-19) patients have a 1.7-fold higher arrhythmia risk with rates of cardiac complications ranging from 2% non-ICU patients to 59% in non-survivors. Atrial fibrillation (AF), the most common arrhythmia, is a frequent complication of acute and long COVID-19. The high expression of ACE2 in the heart suggested that infectious virus may underlie cardiac complications. However, we recently reported in human cardiac tissue from fatal COVID-19 cases perivascular spike protein, elevated pro-inflammatory cytokines, vascular damage, and cardiac remodeling without evidence for direct infection of cardiac cells by SARS-CoV2. Mislocalization of intercalated disc (ID) components, connexin-43 (Cx43) gap junctions and NaV1.5 sodium channels, was also evident in patients' hearts, recapitulating structural remodeling we previously identified as providing a substrate for atrial arrhythmias following an acute inflammatory insult. Therefore, we hypothesized that the inflammatory response elicited by SARS-CoV2 spike protein is sufficient to provoke atrial arrhythmias. Structural and functional assessments of WT murine hearts were performed five days following a single bolus intravenous injection of the viral spike protein. In vivo ECGs demonstrated increased atrial arrhythmia burden in spike-injected mice vs. control. Immunohistochemistry studies revealed elevated expression of inflammatory markers and evidence of vascular damage in these mice. Additionally, we observed disruption of ID ultrastructure and mislocalization of Cx43 and NaV1.5 in the atria of spike protein-injected mice. Our results suggest that vascular-leak inducing inflammatory insult from viral spike protein, and not direct infection by SARS-CoV2 results in the pathophysiology of cardiac dysfunction in fatal COVID-19.},
}
@article {pmid41026737,
year = {2025},
author = {Yaker, N},
title = {Performing a Nonsurgical Hair Restoration Consultation.},
journal = {Plastic and aesthetic nursing},
volume = {45},
number = {4},
pages = {228-239},
pmid = {41026737},
issn = {2770-3517},
mesh = {Humans ; *Alopecia/therapy/nursing ; *Referral and Consultation ; COVID-19/complications ; *Hair/growth &amp; development ; },
abstract = {The condition of an individual's skin and hair is an indication of the state of the physiological mechanisms inside their body. Practitioners performing hair restoration consultations should have a clear understanding of the anagen, catagen, and telogen phases of the hair growth cycle and a clear comprehension about the various types and causes of hair loss, including the use of glucagon-like peptide-1 medications and the effects of Long COVID. Nurses can use the Assessment, Diagnosis, Planning, Implementation, and Evaluation nursing process format when providing a professional hair consultation. The goal of this manuscript is to teach aesthetic practitioners how to conduct a thorough nonsurgical hair restoration consultation.},
}
@article {pmid41025260,
year = {2025},
author = {Björnson, M and Wijnbladh, K and Törnberg, A and Svensson-Raskh, A and Svensson, A and Ståhlberg, M and Runold, M and Fedorowski, A and Nygren-Bonnier, M and Bruchfeld, J},
title = {Prevalence and Clinical Impact of Postural Orthostatic Tachycardia Syndrome in Highly Symptomatic Long COVID.},
journal = {Circulation. Arrhythmia and electrophysiology},
volume = {18},
number = {10},
pages = {e013629},
doi = {10.1161/CIRCEP.124.013629},
pmid = {41025260},
issn = {1941-3084},
mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/epidemiology/diagnosis/physiopathology ; Female ; *COVID-19/epidemiology/diagnosis/complications/physiopathology ; Male ; Prevalence ; Adult ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; Tilt-Table Test ; },
abstract = {BACKGROUND: The incidence of postural orthostatic tachycardia syndrome (POTS) in long COVID has been a growing concern since the first cases were reported in 2021. The aim of this study was to assess the prevalence and clinical impact of POTS in a series of well-characterized patients with long COVID.<br><br>METHODS: We prospectively analyzed 467 nonhospitalized, highly symptomatic (sick leave &#x2265;50%) patients with long COVID, and studied differences in demographics and clinical assessment outcomes between those diagnosed with POTS and the remaining long COVID patients. Examinations were performed at a median of 12 months after acute COVID-19, followed by a cardiologist evaluation with 48-hour ECG, head-up tilt test, and Active Stand Test for those with clinically suspected POTS.<br><br>RESULTS: Of all long COVID patients, 143 (31%) were diagnosed with POTS, 128 (27%) did not fulfill POTS criteria, while 196 (42%) had no clinical signs of POTS. Patients with POTS were younger (mean age, 40.0 versus 44.0 versus 47.0 years, respectively; P&#x2264;0.001) and predominantly female (91%). They had significantly lower physical activity compared with the other 2 groups, as measured with the Fr&#xe4;ndin-Grimby scale (P=0.001). Heart rates during the 6-minute walk test were significantly higher in the POTS group, both during walking and at rest afterward, with a significantly shorter walking distance (448 m versus 472 m versus 509 m, respectively; P&#x2264;0.001). However, the distribution of symptoms showed no significant differences between the groups.<br><br>CONCLUSIONS: In this cohort of predominantly younger women with highly symptomatic long COVID, POTS is common and presents with overlapping symptoms between POTS and non-POTS patients. Long COVID POTS confers lower physical activity and capacity compared with non-POTS long COVID and should be systematically assessed in this condition.},
}
@article {pmid41023887,
year = {2025},
author = {Guillen-Burgos, HF and Sarmiento, M and Gálvez-Flórez, JF and Rojas, C and Lora, YB and Lozada-Martinez, ID and Diazgranados-Garcia, MC and Gibacus, and Rojas, M and Salazar-Uribe, JC and Anaya, JM},
title = {Association between mental health symptoms and autoimmunity in patients with long COVID.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1220},
pmid = {41023887},
issn = {1471-2334},
support = {PCS-MHO-001//Universidad Simon Bolivar/ ; INV-101//COOSALUD EPS/ ; INV-101//COOSALUD EPS/ ; INV-101//COOSALUD EPS/ ; INV-101//COOSALUD EPS/ ; },
mesh = {Humans ; Male ; *COVID-19/psychology/immunology/complications/epidemiology ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; Autoantibodies/blood/immunology ; *Anxiety/immunology/epidemiology ; *Autoimmunity ; Sleep Initiation and Maintenance Disorders/immunology ; *Depression/immunology/epidemiology ; SARS-CoV-2 ; Aged ; Colombia/epidemiology ; Mental Health ; Antibodies, Antinuclear/blood ; },
abstract = {BACKGROUND: Neuropsychiatric symptoms are common features in long COVID. The pathogenesis of neuropsychiatric manifestations in both acute COVID-19 and long COVID remains unclear. This study aimed to examine mental health symptoms-depressive, anxiety, and insomnia symptoms-in COVID-19 survivors with long COVID, and to explore their potential association with autoimmune activity.<br><br>METHODS: We conducted an observational, cross-sectional study of 228 adults recruited from a long COVID program in Cartagena, Colombia. Participants underwent clinician-administered interviews and completed validated psychometric scales to assess depressive (PHQ-9), anxiety (GAD-7), and insomnia (ISI) symptoms. Sociodemographic, clinical, and biological data were collected. The autoantibody panel included antinuclear antibodies (ANA), anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Smith (Sm), rheumatoid factor (RF), anti-thyroglobulin (Tg), and anti-thyroid peroxidase (TPO), measured via ELISA and immunofluorescence. Robust logistic regression models were used to evaluate associations between long COVID, autoantibody positivity, and mental health symptoms, adjusting for age, sex, and relevant covariates.<br><br>RESULTS: 57% of participants with a history of COVID-19 acute infection reported long COVID. In participants with long COVID, we reported high proportions of depressive (21.2%), anxiety (31.2%), and insomnia (28.7%) symptoms. Moreover, an association of all three mental health symptoms with autoantibody positivity (particularly antinuclear antibodies [ANA] isolated or co-occurring with anti-TPO antibodies) was observed in individuals with long COVID. Our findings suggest a potential association between psychopathological symptoms, autoantibody positivity, and distinct clinical profiles of long COVID, warranting further longitudinal investigation.<br><br>CONCLUSIONS: Mental health symptoms (MHS) should be considered one of the main targets involved in translational research in long COVID. There is an urgent need for consultation-liaison physicians to work closely with immunologists, rheumatologists, and pain medicine physicians in clinical settings as well as in research. This will contribute to a better understanding of the impact of MHS during illness in long COVID variants.},
}
@article {pmid41023255,
year = {2025},
author = {Lee, J and Rojas, NK and Pinto Pereria, SM and Stephenson, T and McGowan, J and Chalder, T and Dalrymple, E and Ford, T and Heyman, I and Ladhani, S and McOwat, K and Simmons, R and Swann, O and , and Shafran, R},
title = {Mental health of children and young people with pre-existing eating problems during the COVID-19 pandemic.},
journal = {Eating and weight disorders : EWD},
volume = {30},
number = {1},
pages = {77},
pmid = {41023255},
issn = {1590-1262},
support = {COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//UK Research and Innovation/ ; MR/P020372/1//UK Medical Research Council Career Development Award/ ; MR/Y009398/1//Senior Non-clinical fellowship/ ; },
mesh = {Humans ; *COVID-19/psychology ; Female ; Child ; *Feeding and Eating Disorders/psychology/epidemiology ; Adolescent ; Male ; *Mental Health ; Retrospective Studies ; Surveys and Questionnaires ; SARS-CoV-2 ; Young Adult ; Pandemics ; },
abstract = {OBJECTIVE: The study sought to explore mental health trajectories of children and young people (CYP) who retrospectively reported eating problems prior to the pandemic, over a 2-year period (2021-23). Given the rapid increase in eating disorder presentations during the pandemic, these CYP may be particularly susceptible to pandemic-related challenges, including social and functional restrictions.<br><br>METHODS: Data on 2023 CYP from the Children and Young People with Long COVID (CLoCk) study recruited Jan-March 2021 who completed questionnaires at 3-, 6-, 12-, and 24-months post SARS-CoV-2 PCR-testing were analysed. Associations between baseline eating problems (N&#x2009;=&#x2009;241) and emotional and behavioural symptoms (measured by the Strengths and Difficulties Questionnaire (SDQ) total difficulties and impact scores) at each time-point were examined by regression models. Multi-level models were used to determine whether SDQ total and impact trajectories of those with/without prior self-reported eating problems differed.<br><br>RESULTS: Compared to CYP who did not report pre-existing eating problems, those that did had more mental health difficulties at all time points: reflected in significantly higher SDQ total difficulties and impact scores. However, mental health scores of CYP reporting pre-pandemic eating problems were stable over time. Whereas, CYP without eating problems had a slight increase in mental health difficulties over time. Differences between groups diminished but remained significant when controlling for potential confounding variables including prior mental health difficulties.<br><br>DISCUSSION: Young people with eating problems had more emotional and behavioural symptoms during 2021-23, compared with those that did not have eating problems. However, mental health did not worsen over time amongst CYP with pre-existing eating problems, providing evidence of some relative resilience to the effects of the pandemic in this population.<br><br>PUBLIC SIGNIFICANCE: Eating disorders are a major public health concern and presentations have remained high since the Covid-19 pandemic. Understanding how eating difficulties relate to mental health symptomology over time has implications for service planning.<br><br>LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort study.},
}
@article {pmid41021660,
year = {2025},
author = {Carazo, S and Phimmasone, J and Skowronski, DM and Giguère, K and Ouakki, M and Talbot, D and Guay, CA and Sauvageau, C and Brousseau, N and De Serres, G},
title = {Effectiveness of COVID-19 vaccination and prior infections to reduce long COVID risk during the pre-Omicron and Omicron periods.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf549},
pmid = {41021660},
issn = {1537-6591},
abstract = {BACKGROUND: We estimated vaccine effectiveness (VE) against COVID-19 and long COVID during pre-Omicron and Omicron periods, by number of doses and prior infection history.<br><br>METHODS: We combined survey information from a cohort of healthcare workers in Quebec, Canada, with immunization registry and laboratory administrative data. We defined COVID-19 cases as symptomatic laboratory-confirmed infections and long COVID as self-reported symptoms persisting &#x2265;12 weeks. We assessed VE against COVID-19 and long COVID, stratified by infection history, using a test-negative design where vaccinated participants were compared to unvaccinated participants during the pre-Omicron period or to those twice vaccinated &#x2265;6 months before laboratory testing during the Omicron period.<br><br>RESULTS: Analyses included 8230 COVID-19 participants and 43361 tested specimens. During the pre-Omicron period, one- and two-dose VE was 75% (95%CI:64-83) and 95% (95%CI:84-98) against COVID-19, respectively, and 91% (95%CI:79-96) and 87% (95%CI:22-98) against long COVID, respectively. During the Omicron period, booster dose VE was 41% (95%CI:34-47) against COVID-19 and 57% (95%CI:46-66) against long COVID, waning by 6 months. Hybrid VE in vaccinated and previously infected individuals ranged 81% (95%CI:38-94) to 92% (95%CI:87-95) regardless of number of doses, prior infecting variant or median time since last immunological event up to 9 months.<br><br>CONCLUSION: COVID-19 vaccination prevented long COVID during the pre-Omicron period and reduced the risk by more than half post-Omicron. With most of the population by now both vaccinated and infected, repeated booster doses may add little incremental value against long COVID, an observation with important public health, immunization program and cost implications.},
}
@article {pmid41019063,
year = {2025},
author = {Indolfi, C and Klain, A and Dinardo, G and Grella, C and Marrapodi, MM and Miraglia Del Giudice, M},
title = {Commentary: Long COVID in pediatric age: an observational, prospective, longitudinal, multicenter study in Italy.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1624011},
pmid = {41019063},
issn = {1664-3224},
}
@article {pmid41018705,
year = {2025},
author = {Hou, Y and Gu, T and Ni, Z and Shi, X and Ranney, ML and Mukherjee, B},
title = {Global Prevalence of Long COVID, Its Subtypes, and Risk Factors: An Updated Systematic Review and Meta-analysis.},
journal = {Open forum infectious diseases},
volume = {12},
number = {9},
pages = {ofaf533},
pmid = {41018705},
issn = {2328-8957},
abstract = {BACKGROUND: This mega-systematic review evaluated the global prevalence of long COVID and its subtypes and symptoms, and assessed the effects of risk factors for long COVID.<br><br>METHODS: Studies published from 5 July 2021 to 29 May 2024 were searched in PubMed, Embase, and Web of Science, with supplemental updates on 23 July 2024. Data were pooled using a random-effects framework with DerSimonian-Laird estimator. Risk of bias analysis was conducted.<br><br>RESULTS: A total of 429 studies were meta-analyzed. The global pooled long COVID prevalence was 36% (95% confidence interval [CI], 33%-40%) with 144 contributing studies. The highest prevalence rates were observed in South America (51% [95% CI, 35%-66%]). The prevalence of long COVID persisted over time, with 35% (95% CI, 31%-39%) at <1 year of follow-up and 46% (95% CI, 37%-57%) at 1-2 years. The most prevalent subtypes were respiratory (20% [95% CI, 14%-28%]) estimated from 31 studies, general fatigue (20% [95% CI, 18%-23%]) from 119 studies, psychological (18% [95% CI, 11%-28%]) from 10 studies, and neurological (16% [95% CI, 8%-30%]) from 23 studies. The 3 strongest risk factors were being unvaccinated for COVID-19 (pooled odds ratio [OR], 2.09 [95% CI, 1.55-2.81]) meta-analyzed from 7 studies, infections from pre-Omicron variants (OR, 1.74 [95% CI, 1.40-2.17]) from 6 studies, and female sex (OR, 1.56 [95% CI, 1.32-1.84]) from 33 studies.<br><br>CONCLUSIONS: Long COVID is globally prevalent after a severe acute respiratory syndrome coronavirus 2 infection, highlighting a continuing health challenge. The heterogeneity of estimates across populations argues the need for well-designed follow-up studies that use consistent measures and are globally representative.},
}
@article {pmid41018694,
year = {2025},
author = {de Lemos Muller, CH and Pohl, HH and Reckziegel, MB},
title = {Prevalence and clinical profile of COVID-19 among farmworkers from the interior of the state of Rio Grande do Sul, Brazil.},
journal = {Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT},
volume = {23},
number = {3},
pages = {e20251444},
pmid = {41018694},
issn = {1679-4435},
abstract = {INTRODUCTION: Farmworkers in Brazil face poor living conditions, limited healthcare access, and high prevalence of chronic diseases. These vulnerabilities may increase COVID-19 risk, complications, and persistent symptoms, underscoring the importance of characterizing the disease's impact in this population.<br><br>OBJECTIVES: To identify the prevalence and clinical profile of COVID-19 among farmworkers of cities that participate of the Conselho Regional de Desenvolvimento do Vale do Rio Pardo.<br><br>METHODS: A retrospective cross-sectional study that utilized a database from a research performed with rural workers of cities from Conselho Regional de Desenvolvimento do Vale do Rio Pardo. Hundred seven volunteers were included (54.01 &#xb1; 13.02 years) who answered the questionnaries of life style and COVID-19, in addition to having performed body composition assessment. Prevalence ratio was measured to verify association between risk factors and COVID-19 diagnosis.<br><br>RESULTS: Twenty-five people (23.36%) were diagnosticated with COVID-19. The more described symptoms were fatigue (84%), fever (68%), cough (68%), loss of taste (68%), headache (68%), and sore throat (64%). None of the participants was hospitalized. Symptoms of long covid were observed in 52% participants, with fatigue (24%) and breathless (16%) being the most prevalent. The results showed positive association between COVID-19 diagnosis and hypertension (prevalence ratio 1.23), cancer (prevalence ratio 1.22) and obesity (prevalence ratio 1.76).<br><br>CONCLUSIONS: The results help to characterize the clinical profile of the disease in a population with less access to health services.},
}
@article {pmid41017688,
year = {2025},
author = {Mahoney, J and Shatri, G and Simmer, PE and Doherty, D and Matta, V and Valentino, DJ},
title = {Retrospective analysis of patients with cardiopulmonary symptoms in the setting of Long COVID syndrome: investigating risk factors.},
journal = {Journal of osteopathic medicine},
volume = {},
number = {},
pages = {},
pmid = {41017688},
issn = {2702-3648},
abstract = {CONTEXT: Long COVID, a debilitating condition characterized by persistent symptoms following acute Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, continues to pose a significant public health burden. Currently, research is ongoing regarding risk factors for developing Long COVID. Identifying patients susceptible to symptoms of Long COVID can assist with identifying those at risk, and developing preventative strategies for these individuals.<br><br>OBJECTIVES: The objectives of this study are to evaluate a cohort of patients who followed up in the Long COVID clinic who were experiencing cardiopulmonary symptoms 8-12&#xa0;weeks from initial inoculation, and to retrospectively identify any statistically significant risk factors or clinical features present.<br><br>METHODS: This retrospective cohort study examined patients identified between April 2021 and September 2022. Patients who were diagnosed with COVID-19 and developed persistent symptoms were subsequently referred to the post-COVID-19 pulmonary clinic. For the cohort of patients seen in post COVID-19 pulmonary clinic, pre-existing pulmonary and systemic disease, severity of COVID-19 illness, and treatments received were examined. Analysis was performed on these data utilizing Cox regression analysis.<br><br>RESULTS: Two hundred forty-six (246) adult patients who had Long COVID symptoms 8-12&#xa0;weeks post-COVID-19 infection were identified and included in this analysis. Cox regression analysis indicated that in this population, patients who had required oxygen support (supplemental oxygen, noninvasive ventilation, or intubation) during their initial COVID-19 hospitalization and who also had prior history of either obstructive sleep apnea (OSA) or chronic obstructive pulmonary disease (COPD) and were more likely to develop Long COVID symptoms. Patients with pre-existing OSA had an odds ratio (OR) of 3.6 and a 95&#x202f;% confidence interval (CI) of 1.70-7.65 (p=0.0012). Patients with pre-existing COPD had an OR of 12.19 and a 95&#x202f;% CI of 2.38-62.33 (p=0.0015).<br><br>CONCLUSIONS: Patients who required oxygen support during their initial COVID-19 hospitalization who also had previous history of either OSA or COPD were more likely to develop cardiopulmonary Long COVID symptoms. This suggests that pre-existing respiratory conditions and the severity of the initial COVID-19 illness may influence the development of these symptoms of Long COVID.},
}
@article {pmid41013344,
year = {2025},
author = {Nji, MAM and Briones, EM and Issa, A and Tierney, M and Bertolli, J and Barshikar, S and Unger, ER and Wisnivesky, J and Vu, Q and Quimby, D and Abrams, J and Jagan, N and Manouchehripour, S and Laguerre, M and Cope, JR},
title = {Medical complexity and healthcare utilization among patients attending three U.S. post-COVID clinics.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1145},
pmid = {41013344},
issn = {1471-2334},
mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology/therapy ; Adult ; Aged ; Retrospective Studies ; Aged, 80 and over ; Adolescent ; Young Adult ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; SARS-CoV-2 ; United States/epidemiology ; Texas/epidemiology ; },
abstract = {BACKGROUND: Patients who do not fully recover or develop new symptoms following SARS-CoV-2 infection require follow-up and sometimes seek care at specialized multidisciplinary care clinics. We aimed to describe the clinical characteristics and care needs of patients at three such post-COVID clinics.<br><br>METHODS: We conducted a multisite retrospective electronic chart review of 984 patients, aged&#x2009;&#x2265;&#x2009;18 years, who visited one of three post-COVID clinics at least 28 days after a clinical or polymerase chain reaction (PCR)-confirmed diagnosis of SARS-CoV-2 infection between January 20, 2020, and March 31, 2021. The clinics were located in Omaha, Nebraska, New York City, New York, and Dallas, Texas. Patient records were obtained through September 30, 2021. Data on clinical evaluations and healthcare provider visits were abstracted by trained clinical personnel using a standardized health record abstraction tool.<br><br>RESULTS: The median age was 52 years (range 18-89 years), 59.9% were female, and 69.0% were White. Of 984 patients, 79.9% had SARS-CoV-2 infection that was confirmed by PCR, 32.1% had three or more comorbid conditions, and 39.4% had been hospitalized. During post-COVID follow-up, the most common symptoms were shortness of breath (59.2%), post-exertional malaise (45.6%), fatigue (43.2%), and brain fog (42.8%). Nearly one in three patients had a diagnosis of post-viral fatigue syndrome (30.1%), and pulmonary system conditions (24.4%) were also common. Overall, the 984 participants attended 3914 visits (median 3; range 1-46) over a median follow-up period of 107 days (range 1-560) between first and last post-COVID follow-up visits. Of the 984 patients, 64.3% were referred for subspecialty care notably pulmonology, cardiology, and neurology. More than a third of patients were referred for rehabilitation therapy (37.9%) including physical, occupational, speech, and psychotherapy.<br><br>CONCLUSION: Adult patients at post-COVID clinics have a wide range of symptoms and conditions that highlight the medical complexity of these patients and their need for high levels of care, including multiple health care visits and referrals for therapy. This underscores the need for well-coordinated, multidisciplinary care, and planning of health resources for post-COVID-19 follow-up care.},
}
@article {pmid41012643,
year = {2025},
author = {Yang, YF and Ling, MP and Chen, SC and Lin, YJ and You, SH and Lu, TH and Chen, CY and Wang, WM and Chen, SY and Lai, IH and Hsiao, HA and Liao, CM},
title = {Biomarker-Based Risk Assessment Strategy for Long COVID: Leveraging Spike Protein and Proinflammatory Mediators to Inform Broader Postinfection Sequelae.},
journal = {Viruses},
volume = {17},
number = {9},
pages = {},
pmid = {41012643},
issn = {1999-4915},
support = {NSTC 113-2313-B-002-032//National Science and Technology Council/ ; },
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism/blood ; *COVID-19/diagnosis/virology/immunology ; *Biomarkers/blood ; Risk Assessment ; SARS-CoV-2 ; Male ; Middle Aged ; Female ; Models, Theoretical ; Interleukin-6/blood ; *Inflammation Mediators/blood ; Cytokines/blood ; Post-Acute COVID-19 Syndrome ; Interleukin-8/blood ; Tumor Necrosis Factor-alpha/blood ; Aged ; Adult ; },
abstract = {Long COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, has emerged as a significant public health challenge with wide-ranging clinical and socioeconomic implications. Developing an effective risk assessment strategy is essential for the early identification and management of individuals susceptible to prolonged symptoms. This study uses a quantitative approach to characterize the dose-response relationships between spike protein concentrations and effects, including Long COVID symptom numbers and the release of proinflammatory mediators. A mathematical model is also developed to describe the time-dependent change in spike protein concentrations post diagnosis in twelve Long COVID patients with a cluster analysis. Based on the spike protein concentration-Long COVID symptom numbers relationship, we estimated a maximum symptom number (~20) that can be used to reflect a persistent predictor. We found that among the crucial biomarkers associated with Long COVID proinflammatory mediator, CXCL8 has the lowest 50% effective dose (0.01 μg mL[-1]), followed by IL-6 (0.39), IL-1β (0.46), and TNF-α (0.56). This work provides a comprehensive risk assessment strategy with dose-response tools and mathematical modeling developed to estimate potential spike protein concentration. Our study suggests persistent Long COVID guidelines for personalized care strategies and could inform public health policies to support early interventions that reduce long-term disability and healthcare burdens with possible other post-infection syndromes.},
}
@article {pmid41012598,
year = {2025},
author = {Khaidarov, S and Hejran, AB and Moldakaryzova, A and Izmailova, S and Nurgaliyeva, B and Beisenova, A and Mustafaeva, A and Nurzhanova, K and Belova, Y and Satbayeva, E and Aidarov, A and Ossikbayeva, S and Kukubassov, Y and Amankulov, J and Goncharova, T and Yeszhan, B and Tulman, E and Tazhibayeva, KN and Sadykova, A and Kozhabergenov, N and Burashev, Y},
title = {An Anti-HIV Drug Is Highly Effective Against SARS-CoV-2 In Vitro and Has Potential Benefit for Long COVID Treatment.},
journal = {Viruses},
volume = {17},
number = {9},
pages = {},
pmid = {41012598},
issn = {1999-4915},
mesh = {*SARS-CoV-2/drug effects ; Chlorocebus aethiops ; Vero Cells ; Animals ; *COVID-19 Drug Treatment ; *Tenofovir/pharmacology/analogs &amp; derivatives ; *Antiviral Agents/pharmacology ; Humans ; Viral Load/drug effects ; Alanine ; *Anti-HIV Agents/pharmacology ; COVID-19/virology ; *Adenine/analogs &amp; derivatives/pharmacology ; Drug Repositioning ; Virus Replication/drug effects ; },
abstract = {The persistent evolution of SARS-CoV-2 necessitates novel antiviral strategies. This study evaluated the anti-HIV prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for repurposing against SARS-CoV-2, assessing key pharmacological indices (CC50, EC50, cytostatic effect, and therapeutic window). In vitro screening in Vero E6 cells measured cytotoxicity (via CCK-8/MTT assays) and antiviral activity against Kazakh B.1 and Wuhan strains. TDF (50 µg/mL) reduced high viral loads (MOI 2) by ~2 log10 (100% inhibition), with minimal cytotoxicity (≥75% viability). TAF achieved near-complete suppression (100% inhibition) at 50 µg/mL, exhibiting dose-dependent inhibition (68-100%) at lower viral loads (MOI 0.01). Both prodrugs showed enhanced antiviral activity with prolonged exposure (96 h). Synergy assessments demonstrated favourable combination indices (CI < 1). Electron microscopy confirmed virion integrity post-treatment. These findings highlight TDF and TAF as promising candidates against SARS-CoV-2, with particular potential for targeting lymphoid reservoirs-sites implicated in persistent viral reservoirs that may contribute to long COVID pathogenesis. Further clinical validation is warranted.},
}
@article {pmid41012111,
year = {2025},
author = {Arévalo-Genicio, A and García-Arqué, MC and Gragea-Nocete, M and Llistosella, M and Moro-Casasola, V and Pérez-Díaz, C and Puigdellívol-Sánchez, A and Roca-Puig, R},
title = {Long COVID Syndrome Prevalence in 2025 in an Integral Healthcare Consortium in the Metropolitan Area of Barcelona: Persistent and Transient Symptoms.},
journal = {Vaccines},
volume = {13},
number = {9},
pages = {},
pmid = {41012111},
issn = {2076-393X},
support = {PT-082023-EP subproject COVID-P//Government of Catalonia/ ; },
abstract = {BACKGROUND: Long COVID can persist for years, but little is known about its prevalence in relation to the number of infections. This study examines the prevalence of long COVID in association with the number of infections and vaccination status.<br><br>METHODS: We analyzed anonymized data on long COVID cases, thrombotic events and polypharmacy from March 2020, provided by the Data Analysis Control Department for the population assigned to the CST (192,651 at March 2025). Additionally, we analyzed responses to a long COVID symptom-specific survey distributed in March 2024 to individuals aged 18 to 75 years from the CST population diagnosed with COVID-19 as of December 2023 (n = 43,398; 3227 respondents). Symptomatic patients suspected of having long COVID underwent blood tests to exclude alternative diagnoses.<br><br>RESULTS: The overall detected prevalence of long COVID was 2.4&#x2031;, with higher frequency among women aged 30-59 years (p < 0.001). The survey, combined with specific blood tests, improved detection rates by 26.3%. Long COVID prevalence was 3-10 times higher in individuals with three or more infections than in those with only one recorded infection (based on survey/CST data, respectively). The absolute number of thrombotic events among individuals aged >60 doubled from 2020 to 2024, occurring in both vaccinated and unvaccinated individuals, as well as in those with or without prior documented COVID-19 infection, including in patients without chronic treatments.<br><br>CONCLUSIONS: We found a link between SARS-CoV-2 reinfection and long COVID, and a post-pandemic rise in thrombotic events across all populations, regardless of vaccination or prior infection. Findings support continued COVID-19 diagnosis in suspected cases and mask use by healthcare workers treating respiratory patients.},
}
@article {pmid41012107,
year = {2025},
author = {Shakib, SH and Karimi, SM and McGeeney, JD and Parh, MYA and Zarei, H and Chen, Y and Goldman, B and Novario, D and Schurfranz, M and Warren, CA and Antimisiaris, D and Little, BB and McKinney, WP and Graham, AJ},
title = {Local Health Department COVID-19 Vaccination Efforts and Associated Outcomes: Evidence from Jefferson County, Kentucky.},
journal = {Vaccines},
volume = {13},
number = {9},
pages = {},
pmid = {41012107},
issn = {2076-393X},
support = {OGMB220965A//American Rescue Fund/ ; OGMB220965B//Centers for Disease Control and Prevention (CDC)/ ; },
abstract = {Background: While disparities in vaccine uptake have been well documented, few studies have evaluated the impact of local vaccine programs on COVID-19 outcomes, namely cases, hospitalizations, and deaths. Objectives: Evaluate the impact of COVID-19 vaccine doses coordinated by the Louisville Metro Department of Public Health and Wellness (LMPHW) on COVID-19 outcomes by race across ZIP codes from December 2020 to May 2022 in Jefferson County, Kentucky. Methods: Fixed-effects longitudinal models with ZIP codes as ecological time-series units were estimated to measure the association between COVID-19 vaccine doses and outcomes with time lags of one week, two weeks, three weeks, four weeks, and one month. Models were adjusted for time (week or month of the year) and its interaction with ZIP code. Results: In the one-week lag model, significant negative associations were observed between LMPHW-coordinated vaccine doses and COVID-19 outcomes, indicating reductions of 11.6 cases, 0.4 hospitalizations, and 0.3 deaths per 100 doses administered. Vaccine doses were consistently associated with fewer deaths among White residents across all lags, with an average reduction of 0.2 deaths per 100 doses. No significant associations were found for Black residents. Temporal trends also indicated declines in COVID-19 outcomes when LMPHW's vaccine administration program peaked, between March and May 2021. Conclusions: Timely uptake of COVID-19 vaccines remains critical in avoiding severe outcomes, especially with emerging variants. Racial disparities in vaccine-outcome associations emphasize the potential need for equitable, community-driven vaccine campaigns to improve population health outcomes.},
}
@article {pmid41011507,
year = {2025},
author = {Maddaloni, L and Bugani, G and Fracella, M and Bitossi, C and D'Auria, A and Aloisi, F and Azri, A and Santinelli, L and Ben M'Hadheb, M and Pierangeli, A and Frasca, F and Scagnolari, C},
title = {Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
pmid = {41011507},
issn = {2076-2607},
support = {RM124190A260C1F0//Sapienza University of Rome/ ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized by pattern recognition receptors (PRRs), which play a vital role in triggering innate immune responses such as the production of type I and III interferons (IFNs). While modest PRR activation helps to defend against SARS-CoV-2, excessive or sustained activation can cause harmful inflammation and contribute to severe Coronavirus Disease 2019 (COVID-19). Altered expression of Toll-like receptors (TLRs), which are among the most important members of the PRR family members, particularly TLRs 2, 3, 4, 7, 8 and 9, has been strongly linked to COVID-19 severity. Furthermore, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), collectively known as RLRs (RIG-I-like receptors), act as sensors that detect SARS-CoV-2 RNA. The expression of these receptors, as well as that of different DNA sensors, varies in patients infected with SARS-CoV-2. Changes in PRR expression, particularly that of TLRs, cyclic GMP-AMP synthase (cGAS), and the stimulator of interferon genes (STING), have also been shown to play a role in the development and persistence of long COVID (LC). However, SARS-CoV-2 has evolved strategies to evade PRR recognition and subsequent signaling pathway activation, contributing to the IFN response dysregulation observed in SARS-CoV-2-infected patients. Nevertheless, PRR agonists and antagonists remain promising therapeutic targets for SARS-CoV-2 infection. This review aims to describe the PRRs involved in recognizing SARS-CoV-2, explore their expression during SARS-CoV-2 infection, and examine their role in determining the severity of both COVID-19 and long-term manifestations of the disease. It also describes the strategies developed by SARS-CoV-2 to evade PRR recognition and activation. Moreover, given the considerable interest in modulating PRR activity as a novel immunotherapy approach, this review will provide a description of PRR agonists and antagonists that have been investigated as antiviral strategies against SARS-CoV-2. This review aims to explore the complex interplay between PRRs and SARS-CoV-2 in depth, considering its implications for prognostic biomarkers, targeted therapeutic strategies and the mechanistic understanding of long LC. Additionally, it outlines future perspectives that could help to address knowledge gaps in PRR-mediated responses during SARS-CoV-2 infection.},
}
@article {pmid41011472,
year = {2025},
author = {Rescalvo-Casas, C and Fernández-Villegas, R and Hernando-Gozalo, M and Seijas-Pereda, L and Lledó García, L and Arendt-Nielsen, L and Cuadros-González, J and Pérez-Tanoira, R},
title = {A Retrospective Study on Coinfections, Antimicrobial Resistance, and Mortality Risk Among COVID-19 Patients (2020-2021) with Consideration of Long-COVID Outcomes.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
pmid = {41011472},
issn = {2076-2607},
abstract = {Coinfections in COVID-19 patients can worsen disease severity by enhancing SARS-CoV-2 replication and proinflammatory cytokine levels. This study analyzes the characteristics of coinfected COVID-19 patients across the pandemic and their association with in-hospital mortality. We retrospectively examined data from 351 COVID-19 patients hospitalized in a Spanish secondary hospital between March 2020 and February-March 2021. Nasopharyngeal swabs from 340 patients were analyzed using multiplex RT-PCR to identify 26 respiratory pathogens. A total of 136 patients were coinfected with 191 bacteria (100 Gram-negative and 91 Gram-positive), 20 viruses, 18 fungi, and 1 protist. In 2021, empirical cephalosporin use increased (p = 0.009). The incidence of enterococcal coinfections tripled from 2020 to 2021 (p < 0.001). In 2021, a greater proportion of patients experienced urine (p = 0.001) and bloodstream (p = 0.010) coinfections. In 2020, there was one bloodstream infection, while in 2021, there were seven, with half of them being fatal. Coinfected patients experienced longer hospital stays and higher odds of long COVID (p < 0.001; p = 0.014; p = 0.045). Non-respiratory coinfections in 2021 correlated with increased mortality (p = 0.002). Antimicrobial resistance remained stable (p = 0.149). The rise in cephalosporin use correlated with increased Enterococcus infections, notably bloodstream infections, which were linked to mortality (p = 0.016). In 2021, coinfections were linked to prolonged hospital stays and an increased risk of mortality in our patient cohort.},
}
@article {pmid41011077,
year = {2025},
author = {Onik, G and Sieroń, K},
title = {Longer Health Resort Therapy Improves Outcomes in Long COVID: A Retrospective Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {9},
pages = {},
pmid = {41011077},
issn = {1648-9144},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; *COVID-19/therapy/complications/physiopathology ; *Health Resorts/statistics &amp; numerical data ; Aged ; Treatment Outcome ; Severity of Illness Index ; SARS-CoV-2 ; Time Factors ; },
abstract = {Background and Objectives: The positive effect of health resort treatment on long COVID symptoms has been demonstrated. However, no previous study has considered therapy duration as a factor determining treatment effectiveness. Therefore, the objective of this study was to determine whether the duration of treatment predicts its effectiveness in individuals with long COVID. Materials and Methods: In this retrospective study, medical records of 119 individuals (68 women and 51 men; mean age 63.04 ± 8.61 years) undergoing health resort treatment for long COVID were analyzed. Participants were divided into two groups based on therapy duration: shorter (Group 1) and prolonged (Group 2). Dyspnea was assessed using the mMRC scale, physical performance with the SPPB, and functional status with the PCFS scale. Additionally, individuals rated symptom severity on 0-10 point scales. Results: Improvement in functional status was greater in individuals with a prolonged stay at the health resort (Group 1: 0.59 ± 0.66 points; Group 2: 1.41 ± 0.65 points; p < 0.001). Changes in the severity of most long COVID symptoms were significantly greater in patients who stayed longer. An extended stay at the health resort was associated with significant improvement in functional status (β = 0.033, p = 0.003) and in most long COVID symptoms, particularly sleep disorders (β = 0.112, p < 0.0001), memory disorders (β = 0.104, p < 0.0001), and headaches (β = 0.103, p < 0.0001). Conclusions: A prolonged stay in a sanatorium exerts a favorable effect on symptom severity in individuals with long COVID. Comprehensive health resort treatment of approximately four weeks is associated with improved functional status and alleviation of neuropsychiatric symptoms. Nevertheless, given the retrospective design of the present study, prospective research is required to validate these findings.},
}
@article {pmid41010719,
year = {2025},
author = {Popa, DI and Buleu, F and Iancu, A and Tudor, A and Williams, CG and Militaru, M and Levai, CM and Buleu, T and Ciolac, L and Militaru, AG and Mederle, OA},
title = {Long COVID and Acute Stroke in the Emergency Department: An Analysis of Presentation, Reperfusion Treatment, and Early Outcomes.},
journal = {Journal of clinical medicine},
volume = {14},
number = {18},
pages = {},
pmid = {41010719},
issn = {2077-0383},
support = {Victor Babes University of Medicine and Pharmacy, Timisoara//Victor Babes University of Medicine and Pharmacy, Timisoara/ ; },
abstract = {Background and Objectives: Long COVID has been linked with persistent neurological symptoms, but data on its effects on acute stroke presentation, management, and outcomes remain unclear. This study aimed to compare the clinical profile, management, and short-term outcome of acute ischemic stroke patients with and without Long COVID. Materials and Methods: A retrospective cohort study was conducted on 132 patients who presented at admission with code stroke alert in our Emergency Department (ED). Out of those, 26 were identified to have the Long COVID condition and assigned to the Long COVID group, and 106 were without the Long COVID condition and assigned to the No Long COVID group. Baseline demographics, stroke severity by NIHSS (National Institutes of Health Stroke Scale), risk factors, admission symptoms, laboratory findings, Emergency department time targets, reperfusion treatments received, and outcomes between the two groups were compared. Results: There were no significant differences between the two groups in age, gender, baseline NIHSS scores, ED time targets, or laboratory values. The proportion of patients with Long COVID significantly increased among non-smokers (Fisher's Exact Test chi-squared, p = 0.027). Also, patients suffering from Long COVID exhibited higher incidences of headache (19.2% compared to 5.7%, OR = 3.97, p = 0.040) and facial drooping (42.3% compared to 19.8%, OR = 2.97, p = 0.022). The mechanical thrombectomy was more frequent among the group with Long COVID (30.8% vs. 16.0%), but this difference was not statistically significant. More hemorrhagic transformations happened in the Long COVID group (26.9% vs. 14.2%, p = 0.143). Discharge rates and hospital length of stay in days were similar between groups. Conclusions: Long COVID patients did not present notable differences in emergency department time targets, baseline stroke severity, or short-term outcomes when presenting with code stroke alert. Nevertheless, specific clinical characteristics-such as elevated occurrences of headache and facial drooping-were more frequently observed in patients with Long COVID, alongside non-significant trends indicating a greater utilization of mechanical thrombectomy and increased rates of hemorrhagic transformation. These results imply that Long COVID may have a subtle impact on stroke presentation and potentially on underlying cerebrovascular susceptibility. Further prospective studies with larger sample sizes are necessary to investigate Long COVID's long-term neurological and vascular consequences.},
}
@article {pmid41009814,
year = {2025},
author = {Polo-Alonso, S and Hernáez, &#xc1; and Dégano, IR and Martí-Lluch, R and Pinsach-Abuin, ML and Elosua, R and Subirana, I and Puigmulé, M and Pérez, A and Cruz, R and Diz-de Almeida, S and Puigdecant, E and Selga, E and Nogues, X and Masclans, JR and Güerri-Fernández, R and Cubero-Gallego, H and Tizon-Marcos, H and Vaquerizo, B and Brugada, R and Ramos, R and Camps-Vilaró, A and Marrugat, J},
title = {Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
pmid = {41009814},
issn = {1422-0067},
support = {CB16/11/00229 and CB16/11/00246//CIBER - Consorcio Centro de Investigaci&#xf3;n Biom&#xe9;dica en Red/ ; 2021SGR144//Ag&#xe8;ncia de Gesti&#xf3; d'Ajuts Universitaris i de Recerca/ ; //Crue-CSIC-Santander FONDO SUPERA COVID-19/ ; 202119-30//Fundaci&#xf3; La Marat&#xf3; de TV3/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; *COVID-19/genetics/epidemiology ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Sex Factors ; Polymorphism, Single Nucleotide ; Aged ; Adult ; Genetic Predisposition to Disease ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; },
abstract = {We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined according to the World Health Organization definition. Global and sex-stratified genome-wide association analyses were conducted by logistic regression models adjusted for age, sex (in the global analysis), and the first 10 principal components. We assessed sex-variant interactions and performed gene-based analyses, gene mapping, and gene-set enrichment analyses. When comparing the 1392 long COVID cases with the non-cases, we identified 23 lead variants from suggestive signals: 13 from the global analysis, 5 from females, and 5 from males. Five variants showed a significant interaction with sex (two in females, three in males). We mapped 15 protein-coding genes related to diseases of the immune and nervous systems and tumoral processes. Notably, CD5 and VPS37C, linked to immune function, were significantly associated with long COVID in men. Our results suggest that persistent immune dysregulation may be involved in the development of precisely defined long COVID.},
}
@article {pmid41009651,
year = {2025},
author = {Santinelli, L and Gentilini Cacciola, E and Bortolani, L and Ridolfi, M and Maddaloni, L and Frasca, F and Fracella, M and Bugani, G and d'Ettorre, G and Mastroianni, CM and Ceccarelli, G and d'Ettorre, G},
title = {Long COVID and Type I IFN Signature in Working-Age Adults: A Cross-Sectional Study.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
pmid = {41009651},
issn = {1422-0067},
support = {The NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseas-es (Project no. PE00000007, INF-ACT).//EU/ ; },
mesh = {*Post-Acute COVID-19 Syndrome/blood/diagnosis/immunology ; *Interferon Type I/genetics ; Cross-Sectional Studies ; Biomarkers/blood ; *Immunity, Innate/genetics ; Humans ; Male ; Female ; Middle Aged ; Aged ; Real-Time Polymerase Chain Reaction ; RNA, Messenger/genetics ; Gene Expression Profiling ; Leukocytes, Mononuclear ; },
abstract = {To investigate relevant biomarkers that might aid in the diagnosis and monitoring of long COVID (LC), an analysis of IFN-α, IFN-β, ISG15, and ISG56 transcripts was performed by Real-Time PCR among people of working age who had been infected with SARS-CoV-2 one year prior to the study [LC and non-long COVID (NLC)]. Despite no differences in the transcript levels of IFN-α, IFN-β, ISG15, and ISG56 between LC and NLC, higher IFN-β mRNA levels were observed among LC compared to NLC individuals who were hospitalized for more than 10 days during acute SARS-CoV-2 infection. Moreover, previously SARS-CoV-2 infected participants that did not require respiratory support and developed LC exhibited higher levels of IFN-α and IFN-β compared to NLC with the same clinical characteristics. These results highlight that SARS-CoV-2 infection leads to changes in peripheral innate immune pathways, which could have implications for the development of LC.},
}
@article {pmid41009608,
year = {2025},
author = {Mantle, D and Domingo, JC and Golomb, BA and Castro-Marrero, J},
title = {Gulf War Illness, Fibromyalgia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Overlap in Common Symptoms and Underlying Biological Mechanisms: Implications for Future Therapeutic Strategies.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
pmid = {41009608},
issn = {1422-0067},
mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/metabolism/pathology/drug therapy ; *Persian Gulf Syndrome/therapy/pathology/metabolism ; Ubiquinone/analogs &amp; derivatives/therapeutic use ; *Fibromyalgia/therapy/metabolism/pathology/drug therapy ; *COVID-19/complications/metabolism/therapy ; Oxidative Stress ; SARS-CoV-2 ; },
abstract = {Although Gulf War Illness (GWI), fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID have distinct origins, in this article we have reviewed evidence that these disorders comprise a group of so-called low-energy associated disorders with overlapping common symptoms underlying pathology. In particular, evidence for mitochondrial dysfunction, oxidative stress, inflammation, immune dysregulation, neuroendocrine dysfunction, disrupted brain-gut-microbiome axis, apoptosis/ferroptosis and telomere shortening as common features in the pathogenesis of these disorders has been identified. Given the role of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, as an antioxidant, antiinflammatory and antiapoptotic and antiferroptotic agent, there is a rationale for supplementary CoQ10 in the management of these disorders. The reported benefits of supplementary CoQ10 administration in GWI, FM, ME/CFS and long COVID have been reviewed; the potential benefit of supplementary CoQ10 in reducing telomere shortening and improving the efficiency of stem cell transfer relevant has also been identified as promising therapeutic strategies in these disorders. This review advances beyond previous systematic reviews and consensus statements on overlapping similar symptoms and underlying biological pathomechanisms in these complex disorders.},
}
@article {pmid41008975,
year = {2025},
author = {Mese, O and Otsuka, Y and Sakurada, Y and Tokumasu, K and Soejima, Y and Morita, S and Nakano, Y and Honda, H and Eguchi, A and Fukuda, S and Nojima, J and Otsuka, F},
title = {Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
pmid = {41008975},
issn = {2076-3921},
support = {2024//Research grant from the Japanese Society of Hospital General Medicine/ ; 23fk0108585h0001, 24lk0310100h0001//Japan Agency for Medical Research and Development/ ; },
abstract = {To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9-627.6], 2385.8 [2169.2-2558.1] and 2.0 [1.7-2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner.},
}
@article {pmid41008646,
year = {2025},
author = {Lee, E and Ozigbo, AA and Varon, J and Halma, M and Laezzo, M and Ang, SP and Iglesias, J},
title = {Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.},
journal = {Biomolecules},
volume = {15},
number = {9},
pages = {},
pmid = {41008646},
issn = {2218-273X},
mesh = {Humans ; *COVID-19/metabolism/complications/pathology ; *Mitochondria/metabolism/pathology ; *Reactive Oxygen Species/metabolism ; SARS-CoV-2/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism ; Post-Acute COVID-19 Syndrome ; Oxidative Stress ; },
abstract = {Post-acute sequelae of SARS-CoV-2 infection (long COVID) present with persistent fatigue, cognitive impairment, and autonomic and multisystem dysfunctions that often go unnoticed by standard diagnostic tests. Increasing evidence suggests that mitochondrial dysfunction and oxidative stress are central drivers of these post-viral sequelae. Viral infections, particularly SARS-CoV-2, disrupt mitochondrial bioenergetics by altering membrane integrity, increasing mitochondrial reactive oxygen species (mtROS), and impairing mitophagy, leading to sustained immune activation and metabolic imbalance. This review synthesizes an understanding of how mitochondrial redox signaling and impaired clearance of damaged mitochondria contribute to chronic inflammation and multisystem organ symptoms in both long COVID and post-vaccine injury. We discuss translational biomarkers and non-invasive techniques, exploring therapeutic strategies that include pharmacological, non-pharmacological, and nutritional approaches, as well as imaging modalities aimed at assessing and restoring mitochondrial health. Recognizing long COVID as a mitochondrial disorder that stems from redox imbalance will open new options for personalized treatment and management guided by biomarkers. Future clinical trials are essential to validate these approaches and translate mitochondrial resuscitation into effective care for patients suffering from long COVID and related post-viral syndromes.},
}
@article {pmid41008398,
year = {2025},
author = {Popa, MV and Buzea, CG and Gurzu, IL and Salim, C and Gurzu, B and Rusu, DI and Ochiuz, L and Duceac, LD},
title = {An Integrated AI Framework for Occupational Health: Predicting Burnout, Long COVID, and Extended Sick Leave in Healthcare Workers.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {18},
pages = {},
pmid = {41008398},
issn = {2227-9032},
abstract = {BACKGROUND: Healthcare workers face multiple, interlinked occupational health risks-burnout, post-COVID-19 sequelae (Long COVID), and extended medical leave. These outcomes often share predictors, contribute to each other, and, together, impact workforce capacity. Yet, existing tools typically address them in isolation.<br><br>OBJECTIVE: The objective of this study to develop and deploy an integrated, explainable artificial intelligence (AI) framework that predicts these three outcomes using the same structured occupational health dataset, enabling unified workforce risk monitoring.<br><br>METHODS: We analyzed data from 1244 Romanian healthcare professionals with 14 demographic, occupational, lifestyle, and comorbidity features. For each outcome, we trained a separate predictive model within a common framework: (1) a lightweight transformer neural network with hyperparameter optimization, (2) a transformer with multi-head attention, and (3) a stacked ensemble combining transformer, XGBoost, and logistic regression. The data were SMOTE-balanced and evaluated on held-out test sets using Accuracy, ROC-AUC, and F1-score, with 10,000-iteration bootstrap testing for statistical significance.<br><br>RESULTS: The stacked ensemble achieved the highest performance: ROC AUC = 0.70 (burnout), 0.93 (Long COVID), and 0.93 (extended leave). The F1 scores were >0.89 for Long COVID and extended leave, whereas the performance gains for burnout were comparatively modest, reflecting the multidimensional and heterogeneous nature of burnout as a binary construct. The gains over logistic regression were statistically significant (p < 0.0001 for Long COVID and extended leave; p = 0.0355 for burnout). The SHAP analysis identified overlapping top predictors-tenure, age, job role, cancer history, pulmonary disease, and obesity-supporting the value of a unified framework.<br><br>CONCLUSIONS: We trained separate models for each occupational health risk but deployed them in a single, real-time web application. This integrated approach improves efficiency, enables multi-outcome workforce surveillance, and supports proactive interventions in healthcare settings.},
}
@article {pmid41007828,
year = {2025},
author = {Dotor-Llerena, AL and Reyes-Long, S and Najera-García, L and Hernández-Corral, S and Arechaga-Ocampo, E and Avendaño-Ortiz, K and Trejo-Martínez, D and Rosell-Becerril, H and Cortes-Altamirano, JL and Alfaro-Rodríguez, A},
title = {The Effect of Neurorehabilitation of the Cognitive Symptoms of Long COVID Evaluated with Neuropsi Atención y Memoria-III and BANFE-III.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
pmid = {41007828},
issn = {2227-9059},
abstract = {Background: The long-haul symptoms of COVID-19 have not been properly attended, especially those of the central nervous system. Attention, memory and executive functioning are the three main cognitive symptoms reported for long COVID patients. To this day, neurorehabilitation therapy to alleviate these symptoms has not been proposed. Objectives: The current study aims to evaluate the effect of a neurorehabilitation intervention on the three most prevalent symptoms reported for long COVID in Mexican patients: memory, attention and executive functioning. Methods: Subjects were recruited at Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra and underwent a novel neurorehabilitation intervention for 6 months. Baseline measurements were taken using validated instruments (Neuropsi, BANFE and CCQ) before the intervention and after it. Results: A significant decrease in the normalized score of the Memory component of the Neuropsi Atención y Memoria III test was found after the intervention, along with a decrease in two components of the BANFE-III test. Conclusions: In the current study, a successful neuropsychology intervention for the main cognitive symptoms of long COVID in a Mexican population reduced subjective self-perceived complaints and objectively measured cognitive symptoms.},
}
@article {pmid41007506,
year = {2025},
author = {Kachroo, P and Boivin, G and Cowling, BJ and Shannon, W and Mallefet, P and Kalita, P and Georgescu, AM},
title = {Long COVID Symptom Management Through Self-Care and Nonprescription Treatment Options: A Narrative Review.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {9},
pages = {},
pmid = {41007506},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/therapy/complications ; *Self Care ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Many patients experience unique or persistent symptoms several months following the onset of infection with severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. While this condition is commonly referred to as long COVID, no universally accepted definition exists; therefore, many patients go underrecognized and underreported. Long COVID can involve almost any major organ system and is characterized by widely heterogeneous persistent or recurrent symptoms including fatigue, headache, cough, dyspnea, chest pain, cognitive dysfunction, anxiety, and depression. In line with the wide array of symptoms, numerous potential underlying pathophysiologic pathways, including viral persistence, prolonged inflammation, autoimmune reactions, endothelial dysfunction, and dysbiosis of the microbiome of the gut, may contribute to the symptomology of long COVID. Therapy is directed at symptomatic control; however, no pharmacologic treatments are specifically approved for the management of symptoms associated with long COVID. Several common symptoms of long COVID may be managed with nonprescription treatments (pharmacologic and nonpharmacologic). The goal of this review is to provide clinicians with a better understanding of long COVID and review the latest recommendations for managing common mild-to-moderate symptoms with nonprescription treatment options.},
}
@article {pmid41007081,
year = {2025},
author = {Goicoechea-Calvo, A and Coll-Fernández, R and Navarro Expósito, N and Colomer Giralt, M and González-Aumatell, A and Méndez-Hernández, M and Carreras-Abad, C and Pallarès Fontanet, N and Tebe Cordomi, C and Durà Mata, MJ and Rodrigo, C},
title = {Effects of Paediatric Post-COVID-19 Condition on Physical Function and Daily Functioning: A Cross-Sectional Study.},
journal = {Children (Basel, Switzerland)},
volume = {12},
number = {9},
pages = {},
pmid = {41007081},
issn = {2227-9067},
abstract = {BACKGROUND/OBJECTIVES: Lack of objective evidence exists regarding changes in physical function and impact on daily functioning in paediatric post-COVID-19 condition (PPCC). This study aimed to assess exercise capacity, fatigue, and peripheral and respiratory muscle strength in PPCC patients compared with healthy controls. Additionally, the impact of PPCC on domains of daily life was evaluated.<br><br>METHODS: A cross-sectional study was performed.<br><br>STUDY VARIABLES: exercise capacity (6 min walk test, 6MWT), inspiratory muscle strength (maximal inspiratory pressure, PImax), handgrip strength (handheld dynamometer, HHD), quadriceps femoris muscle thickness (QF MT), rectus femoris muscle thickness (RF MT), rectus femoris cross-sectional area (RF CSA), rectus femoris echo-intensity (RF EI), fatigue (Paediatric Functional Assessment of Chronic Illness Therapy-Fatigue, pedsFACIT-F), and physical activity (Assessment of Physical Activity Levels Questionnaire, APALQ).<br><br>RESULTS: A total of 115 PPCC patients and 227 healthy controls were included. The PPCC group had lower 6MWT (509.00 &#xb1; 86.12, p < 0.001), PImax (68.71 &#xb1; 26.23, p < 0.001), HHD (82.84 &#xb1; 29.09, p < 0.001), APALQ (7.94 &#xb1; 3.14, p < 0.001), pedsFACIT-F (24.51 &#xb1; 11.01, p < 0.001), QF MT mid-thigh (33.21 &#xb1; 7.99, p = 0.011), and higher RF EI (p < 0.001) vs. controls. Only 37.63% of the PPCC group resumed previous sports, 43.48% were unable to attend school full-time and 28.7% could not participate in after-school activities.<br><br>CONCLUSIONS: Paediatric post-COVID-19 condition patients exhibited significant impairments in terms of physical function, with a high impact on daily functioning. This knowledge is necessary to provide targeted therapeutic interventions.},
}
@article {pmid41004911,
year = {2025},
author = {Chen, TY and Chu, YJ and Hsu, CJ and Wang, HP and Wong, LC and Lee, WT},
title = {Long-Term Influence of Pediatric Long COVID Syndrome on Visual Perception and Neuropsychiatric Symptoms.},
journal = {Pediatric neurology},
volume = {173},
number = {},
pages = {22-29},
doi = {10.1016/j.pediatrneurol.2025.08.018},
pmid = {41004911},
issn = {1873-5150},
mesh = {Humans ; Child ; Male ; *COVID-19/complications/diagnostic imaging/physiopathology/psychology ; Female ; Adolescent ; *Visual Perception/physiology ; Magnetic Resonance Imaging ; *Brain/diagnostic imaging/pathology ; *Gray Matter/diagnostic imaging/pathology ; Neuropsychological Tests ; Severity of Illness Index ; },
abstract = {BACKGROUND: Long COVID presents with a wide range of persistent symptoms and durations following coronavirus disease 2019 (COVID-19) infection. However, data on children and adolescents remain limited. This study aims to explore visual perception and neuropsychiatric symptoms in pediatric patients and examine their associations with brain volume differences.<br><br>METHODS: A total of 60 participants, aged six to 18 years and confirmed COVID-19 antibody positive, were recruited five to eight months after infection. Owing to the diversity of symptoms, each symptom was assigned a weighted score from 0 to 3 based on its severity and relevance to brain function. Participants were then divided into two groups according to symptom severity. All participants underwent magnetic resonance imaging, and the Test of Visual Perceptual Skills-Fourth Edition (TVPS-4) was administered.<br><br>RESULTS: The most common neuropsychiatric symptoms were headache or dizziness, along with attention and memory deficits, which persisted for up to six months. Gray matter volumes were significantly increased in the group with severe symptoms, particularly in subcortical and temporal regions. These brain volume differences showed significant correlations with both acute and chronic symptoms. In the TVPS-4 assessment, significant differences were observed in overall standard scores and in the Sequential Memory subtest between participants with visual-related symptoms and healthy control subjects.<br><br>CONCLUSIONS: Neuropsychiatric symptoms, impaired visual perception, and gray matter volume differences are evident in pediatric long COVID cases. The severity of neuropsychiatric symptoms during the acute phase may predict the degree of chronic-phase brain volume alterations. Longitudinal follow-up studies are essential to validate and expand upon these findings.},
}
@article {pmid41004337,
year = {2026},
author = {Calvache-Mateo, A and Rodríguez-López, A and Navas-Otero, A and Martín Núñez, J and Heredia-Ciuró, A and López-López, L and Valenza, MC},
title = {Impairment of neural mechanosensitivity in the Long COVID haulers.},
journal = {Expert review of respiratory medicine},
volume = {20},
number = {3},
pages = {329-335},
doi = {10.1080/17476348.2025.2568243},
pmid = {41004337},
issn = {1747-6356},
mesh = {Humans ; Male ; Female ; Middle Aged ; Quality of Life ; *COVID-19/physiopathology/complications ; Adult ; Case-Control Studies ; Aged ; *Peripheral Nerves/physiopathology ; },
abstract = {BACKGROUND: The aim of this study was to evaluate and characterize the alteration in mechanosensitivity in Long COVID haulers as well as its impact on patients' functionality and quality of life.<br><br>RESEARCH DESIGN AND METHODS: In this study there were two groups: a group of Long COVID haulers and a group of healthy controls matched for age and sex. The mechanosensitivity clinical profile and peripheral nerve mechanosensitivity were evaluated. The mechanosensitivity clinical profile included the functionality and quality of life (World Health Organization Disability Assessment Schedule 2.0, Patient-Reported Outcomes Measurement Information System, EuroQol-5 Dimensions) and neural mechanosensitivity (Leeds Assessment of Neuropathic Symptoms and Signs). The peripheral nerve mechanosensitivity included neurodynamic tests (median, radial, ulnar, slump test and straight leg raise).<br><br>RESULTS: A total of 64 patients were included in the study (Long COVID haulers group n&#x2009;=&#x2009;33, healthy controls group n&#x2009;=&#x2009;31). Long COVID haulers group obtained significantly worse results in functionality (p&#x2009;<&#x2009;0.001), quality of life (p&#x2009;<&#x2009;0.001), neural mechanosensitivity (p&#x2009;<&#x2009;0.001) and peripheral nerve mechanosensitivity (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Long COVID haulers have significant alterations in neural mechanosensitivity, contributing to a greater degree of functional impairment and poorer quality of life.},
}
@article {pmid41003635,
year = {2025},
author = {Presta, V and Guarnieri, A and Laurenti, F and Mazzei, S and di Martino, O and Vitale, M and Condello, G},
title = {Post-Acute COVID-19 Syndrome (PACS) and Exercise Interventions: A Systematic Review of Randomized Controlled Trials.},
journal = {Sports (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
pmid = {41003635},
issn = {2075-4663},
support = {MUR_DM737_2022_FIL_PROGETTI_B_CONDELLO_COFIN//Bando di Ateneo per la Ricerca 2022 - Azione B/ ; },
abstract = {The aim of this systematic review (PROSPERO registration number CRD42024517069) was to investigate the effectiveness of exercise interventions in Post-Acute COVID-19 Syndrome (PACS). We searched on several databases and followed the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We included randomized controlled trials that evaluate exercise interventions in adults (40-60 years old) diagnosed with PACS. The outcomes of interest were health-related quality of life (HRQoL) and functional fitness. Twenty studies were included after screening. Thirteen and fourteen studies were rated as "low" risk for HRQoL and functional fitness outcomes, respectively. Based on the evidence, an 8-week exercise protocol of aerobic training in combination with strength-based and breathing exercises was found to be safe and feasible while improving quality of life and functional fitness in people with PACS. Telerehabilitation can also be an option to avoid contagion and physical contact with the same beneficial effects. Future research should expand the knowledge about other types of exercise (i.e., water-based exercises) with high-quality trials and consider whether findings could be potentially transferable to recovery from a wider spectrum of viral infections.},
}
@article {pmid41001233,
year = {2025},
author = {Torok, RA and Lubell, J and Rudy, RM and Eccles, J and Quadt, L},
title = {Variant connective tissue as a risk factor for long COVID: a case-control study of data from a retrospective online survey of adults in the USA and UK.},
journal = {BMJ public health},
volume = {3},
number = {2},
pages = {e002949},
pmid = {41001233},
issn = {2753-4294},
abstract = {INTRODUCTION: This study explored the extent to which two measures of joint hypermobility, a marker of variant connective tissue, predict the development of long COVID after COVID-19 infection, and whether the severity of initial COVID-19 symptoms impacts this relationship.<br><br>METHODS: We recruited 1816 participants (352 (19.4%) reporting long COVID&#xfeff;Long COVID, 1464 (80,6%) not reporting long COVIDLong COVID) from the US and UK for a retrospective online survey. The primary outcome was self-reported long COVIDLong COVID, defined as experiencing symptoms related to a COVID-19 infection at least 3&#x2009;months after infection. Secondary outcomes included severity of symptoms during each COVID-19 infection, generalised joint hypermobility (GJH), and the novel concept of 'extreme hypermobility'.<br><br>RESULTS: In separate binomial logistic regressions controlling for sex assigned at birth, age, number of infections and number of vaccine doses, both GJH (OR 1.29, 95%&#x2009;CI 1.00 to 1.65) and extreme hypermobility (OR 2.12, 95%&#x2009;CI 1.43 to 3.16) were found to be predictive of long COVID&#xfeff;&#xfeff;&#xfeff;&#xfeff;&#xfeff;&#xfeff;Long COVID. This likely occurs through two pathways. First, both GJH and extreme hypermobility increase the risk that individuals with no or moderate initial symptoms from a COVID-19 infection experience long COVIDLong COVID. Second, both GJH and extreme hypermobility are significant predictors of developing severe initial symptoms from a COVID-19 infection, which is independently associated with increased long COVID risk. A mediation analysis confirmed that extreme hypermobility influences the odds of developing long COVID in part by increasing the likelihood that individuals experience severe initial symptoms from a COVID infection.<br><br>CONCLUSIONS: Both GJH and extreme hypermobility are significant risk factors for long COVID. People with extreme hypermobility, as newly defined in this study, are at particularly high risk of developing long COVID after an initial COVID-19 infection. Further research is needed to replicate these findings with other datasets, clarify the pathophysiology that explains why people with hypermobility may be at greater risk of long COVID and assess the clinical significance of 'extreme hypermobility'.},
}
@article {pmid41000346,
year = {2025},
author = {Saito, A and Otake, S and Ohgino, K and Bun, S and Mimura, Y and Ito, D and Miyazaki, N and Nagashima, K and Terai, H and Chubachi, S and Masaki, K and Miyata, J and Kawada, I and Namkoong, H and Hashiguchi, M and Kagyo, J and Shiomi, T and Masuzawa, K and Asakura, T and Nakayama, S and Suzuki, Y and Minematsu, N and Manabe, T and Fukui, T and Funatsu, Y and Koh, H and Fukunaga, K},
title = {Anxiety, depression, and fear after coronavirus disease 2019 infection and their association with long coronavirus disease symptoms.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1672447},
pmid = {41000346},
issn = {1664-0640},
abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had widespread physical and psychological repercussions. Additionally, long COVID symptoms such as fatigue, dyspnea, and cognitive impairment have been well-documented; however, their associations with mental health symptoms remain unclear. This study investigated the relationships between long COVID and symptoms of anxiety, depression, and COVID-19-related fear using validated psychological assessment tools.<br><br>METHODS: This nationwide, prospective cohort study enrolled 1,066 individuals who recovered from COVID-19. The participants completed self-report questionnaires at 3, 6, and 12 months after diagnosis. Long COVID symptoms and psychological status were assessed using the Hospital Anxiety and Depression Scale (HADS) and Fear of COVID-19 Scale (FCV-19S). Statistical analyses were used to examine associations between long COVID symptoms and psychological scores while accounting for clinicodemographic factors.<br><br>RESULTS: Three months after diagnosis, 20.1% of the participants exhibited high anxiety (HADS-Anxiety [A] score &#x2265; 8), 23.6% had high depression (HADS-Depression [D] score &#x2265; 8), and 35.3% reported high levels of COVID-19-related fear (FCV-19S score &#x2265; 21). High HADS-A and HADS-D scores were significantly associated with younger age, female sex, and mild initial illness severity. Individuals with high HADS scores reported significantly greater long COVID symptoms; headaches and fatigue were associated with high anxiety scores and impaired concentration was associated with high depression scores.<br><br>CONCLUSIONS: This study highlighted the significant associations between mental health symptoms and long COVID, emphasizing the need for integrated psychological support in post-COVID care. Addressing anxiety, depression, and fear-related concerns may contribute to improved management of long COVID symptoms and enhance overall patient well-being.},
}
@article {pmid40996864,
year = {2025},
author = {Hemming, PE and Arvizu, LS and Yadon, CA},
title = {Sensory and cognitive experiences after COVID-19 infection in college students.},
journal = {Journal of American college health : J of ACH},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/07448481.2025.2561890},
pmid = {40996864},
issn = {1940-3208},
abstract = {OBJECTIVE: This project examined sensory and cognitive processing after COVID-19 infection in college students.<br><br>PARTICIPANTS: The final sample included 424 undergraduate students (M age = 19.36).<br><br>METHODS: A survey was administered to gather demographics, infection history, and sensory and cognitive experiences following COVID-19, including stress, experiential measures of sensory gating and processing, cognition, sleep, olfactory function, and emotional implications.<br><br>RESULTS: Greater perceived COVID-19 severity was significantly associated with poorer sleep quality, sensory processing difficulties, and more cognitive failures. Similarly, participants with lingering symptoms reported significantly poorer sensory, sleep, and cognitive experiences. More difficulty filtering sensory input and poorer sleep predicted higher reported COVID-19 severity. Among those currently experiencing brain fog, greater perceived impact of this symptom was moderately associated with more cognitive failures. Descriptive statistics for emotional implications are provided.<br><br>CONCLUSIONS: Lingering COVID-19 symptoms and perceived severity may be associated with sensory and cognitive challenges in college students.},
}
@article {pmid40996671,
year = {2026},
author = {Gao, Z and Tabernacki, T and Davis, PB and Kaelber, DC and Xu, R},
title = {Associations of selective serotonin reuptake inhibitors and long COVID risk in patients with depression: a retrospective cohort study.},
journal = {Infection},
volume = {54},
number = {1},
pages = {203-211},
pmid = {40996671},
issn = {1439-0973},
support = {R01 AG057557/AG/NIA NIH HHS/United States ; R01 AA029831/AA/NIAAA NIH HHS/United States ; R56 AG062272/AG/NIA NIH HHS/United States ; R01 AG061388/AG/NIA NIH HHS/United States ; RF1 AG076649/AG/NIA NIH HHS/United States ; AA029831/AA/NIAAA NIH HHS/United States ; R01 AG076649/AG/NIA NIH HHS/United States ; AG07664, AG057557, AG061388, and AG062272/AG/NIA NIH HHS/United States ; AG07664, AG057557, AG061388, and AG062272/AG/NIA NIH HHS/United States ; AA029831/AA/NIAAA NIH HHS/United States ; },
mesh = {Humans ; Retrospective Studies ; *Selective Serotonin Reuptake Inhibitors/therapeutic use ; Male ; Female ; *COVID-19/epidemiology/complications ; Middle Aged ; Adult ; *Depression/drug therapy/complications ; Aged ; SARS-CoV-2 ; Risk Factors ; Proportional Hazards Models ; Antidepressive Agents/therapeutic use ; United States/epidemiology ; },
abstract = {PURPOSE: To evaluate the potential of selective serotonin reuptake inhibitors (SSRIs) in reducing the risk of long COVID in patients with depression.<br><br>METHODS: This retrospective cohort study analyzed U.S. electronic health records from TriNetX platform to compare the risk of long COVID among adults with depression who were prescribed SSRIs versus non-SSRI antidepressants between March 2020 and December 2022. The main outcome was the long COVID diagnosis. As a sensitivity analysis, CDC-defined long COVID symptoms were used as alternative outcomes. Cox proportional hazards models were used to assess outcomes occurring 3-6 and 3-12 months after the index SARS-CoV-2 infection, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated.<br><br>RESULTS: After propensity score matching, the study included 31,264 patients, and the risk of long COVID diagnosis was significantly lower in the SSRI cohort compared to the matched non-SSRI antidepressant cohort, with hazard ratios of 0.57 (95% CI: 0.44-0.73) for the 3-6-month period and 0.59 (95% CI: 0.49-0.72) for the 3-12-month period. Sensitivity analyses in matched cohorts of 17,100 patients showed that SSRI use was associated with a significantly reduced risk of long COVID symptoms, consistent across symptom categories and pandemic periods.<br><br>CONCLUSIONS: In adult patients with depression, SSRIs compared with non-SSRI antidepressants were associated with a lower risk of long COVID. These results offer preliminary evidence that SSRIs may help prevent long COVID in high&#x2011;risk populations and warrant further preclinical and clinical investigation.},
}
@article {pmid40996592,
year = {2025},
author = {Zhao, J and Lyu, Y and Qu, J},
title = {Insights into potential therapeutic approaches for long COVID.},
journal = {Frontiers of medicine},
volume = {19},
number = {5},
pages = {879-885},
pmid = {40996592},
issn = {2095-0225},
}
@article {pmid40996585,
year = {2025},
author = {Prociuk, D and Clarke, J and Smith, N and Milne, R and Lee, C and de Lusignan, S and Mir, G and De Kock, J and Mayer, E and Delaney, BC and , },
title = {Understanding the Clinical Characteristics and Timeliness of Diagnosis for Patients Diagnosed With Long Covid: A Retrospective Observational Cohort Study From North West London.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70429},
pmid = {40996585},
issn = {1369-7625},
support = {/WT_/Wellcome Trust/United Kingdom ; //This study was funded by the National Institute for Health and Care Research Ref: COV-LT2-0016. Infrastructure support for this study was provided by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (NIHR203323), the NIHR North-West London Patient Safety Research Collaboration (NIHR NWL PSRC, Ref. NIHR204292) and the NIHR Oxford Biomedical Research Centre. J.C. acknowledges funding from the Wellcome Trust (215938/Z/19/Z)./ ; },
mesh = {Humans ; London/epidemiology ; Retrospective Studies ; Female ; Male ; *COVID-19/diagnosis/epidemiology/complications ; Middle Aged ; Adult ; Aged ; Primary Health Care ; Time Factors ; SARS-CoV-2 ; Incidence ; },
abstract = {BACKGROUND: Long Covid is a multisystem condition first identified in the Covid-19 pandemic, characterised by a wide range of symptoms including fatigue, breathlessness and cognitive impairment. Considerable disagreement exists in who is most at risk of developing long Covid, driven in part by incomplete coding of a long Covid diagnosis in medical records.<br><br>OBJECTIVE: To describe the incidence and impact of long Covid.<br><br>DESIGN: A retrospective observational cohort study.<br><br>SETTING AND PARTICIPANTS: An integrated primary and secondary care dataset from North West London, covering over 2.7 million patients. Patients with long Covid were identified through clinical terms in their primary care records.<br><br>MAIN VARIABLES STUDIED: Multivariate logistic regression was used to identify factors associated with having a long Covid diagnosis, while multivariate quantile regression was used to identify factors predicting the time a long Covid diagnosis was recorded.<br><br>RESULTS: A total of 6078 patients were identified with a long Covid clinical term in their primary care record, 0.33% of the total registered adult population. Women, those aged 41-70&#x2009;years or of Asian or mixed ethnicity, were more likely to have a recorded long Covid diagnosis, alongside those with pre-existing anxiety, asthma, depressive disorder or eczema and those living outside of the least or most socio-economically deprived areas. Men, those aged 41-70&#x2009;years, or of black ethnicity, were diagnosed earlier in the pandemic, while those with depressive disorder were diagnosed later.<br><br>DISCUSSION: Long Covid is poorly coded in primary care records, and significant differences exist between patient groups in the likelihood of receiving a long Covid diagnosis. A recorded long Covid diagnosis is more likely in women, some ethnic minority patients and those with pre-existing long-term conditions.<br><br>CONCLUSION: The experience of patients with long Covid provides a crucial insight into inequities in access to timely care for complex multisystem conditions and the importance of effective health informatics practices to provide robust, timely analytical support for front line clinical services.<br><br>This study was co-designed, conducted and written in conjunction with people with long Covid.},
}
@article {pmid40995517,
year = {2025},
author = {Guo, X and Li, X},
title = {Advances in home-based respiratory muscle training for improving physical function in older adults with long COVID.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1662537},
pmid = {40995517},
issn = {1664-042X},
abstract = {Long COVID imposes a substantial burden on older adults, manifesting as respiratory muscle dysfunction that severely compromises physical function. This narrative review synthesizes current evidence on home-based respiratory muscle training (RMT)-a non-pharmacological intervention targeting this impairment in older patients with long COVID-while critically evaluating its physiological mechanisms, therapeutic efficacy, implementation feasibility, and persistent challenges. Respiratory muscle dysfunction, caused by multifaceted neurophysiological and structural impairments, is a core mechanism of exertional dyspnea and fatigue in older adults, further aggravated by age-related decline. RMT mitigates these effects through improvements in respiratory strength, endurance, ventilatory efficiency, metaboreflex and autonomic regulation, and psychological wellbeing. Home-based RMT demonstrates non-inferior efficacy to conventional programs while providing critical accessibility for mobility-limited older adults. Nevertheless, implementation barriers include challenges in individualizing geriatric-adapted exercise prescriptions, technological access limitations, variable adherence, insufficient clinician training in remote assessment, and regulatory/policy gaps in telerehabilitation frameworks. Despite these challenges, home-based RMT represents a promising strategy for managing debilitating respiratory sequelae in this vulnerable population. This review consolidates RMT's physiological rationale and clinical evidence, underscores its integration potential within collaborative care models, and outlines key translational priorities-including hybrid delivery systems and refined geriatric-specific protocols-to accelerate clinical adoption.},
}
@article {pmid40995223,
year = {2025},
author = {Botelho, MC and Poma, AM and Wu, J},
title = {Editorial: Extrapulmonary manifestations of SARS-CoV-2 infection and COVID-19 vaccine adverse effects.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1688071},
doi = {10.3389/fcimb.2025.1688071},
pmid = {40995223},
issn = {2235-2988},
}
@article {pmid40995163,
year = {2025},
author = {Amedee, RG},
title = {Focusing on Long COVID and HIV Prevention.},
journal = {Ochsner journal},
volume = {25},
number = {3},
pages = {151},
doi = {10.31486/toj.25.5056},
pmid = {40995163},
issn = {1524-5012},
}
@article {pmid40995151,
year = {2025},
author = {Thomas, LDL},
title = {When We Don't Have All the Answers: Long COVID and the Need for Humility in Medicine.},
journal = {Ochsner journal},
volume = {25},
number = {3},
pages = {152-158},
pmid = {40995151},
issn = {1524-5012},
}
@article {pmid40991647,
year = {2025},
author = {Becker, JH and Watson, E and Zubair, N and Carnavali, F and Bagiella, E and Reich, D and Wisnivesky, JP},
title = {Preliminary evaluation of a cognitive rehabilitation intervention for post-COVID-19 cognitive impairment: A pilot randomized controlled trial.},
journal = {Neuropsychological rehabilitation},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09602011.2025.2552154},
pmid = {40991647},
issn = {1464-0694},
abstract = {BACKGROUND: Despite the profound impact of "brain fog" and/or cognitive impairment in relatively young people with Long COVID, no interventions with demonstrated efficacy are currently available. We conducted a pilot randomized controlled trial investigating the preliminary outcomes of a cognitive rehabilitation (CR) intervention adapted for persons with post-COVID cognitive impairment.<br><br>METHODS: Participants were &#x2265;18 years of age, English-speaking, had history of SARS-CoV-2, and had cognitive impairment on objective measures. Eligible participants were randomized to a 12-week CR intervention or a time - and attention-matched control arm. Objective and subjective cognitive functioning was assessed at pre - and within 2-weeks post-intervention, utilizing validated neuropsychological measures across multiple domains. We compared pre vs. post intervention changes in cognitive scores in intervention vs. control groups.<br><br>RESULTS: The mean change in the intervention group compared to the controls in measures of processing speed, learning, memory, language, and of executive function did not reach the threshold for futility. In comparison to controls, the intervention group self-reported significant improvements in cognitive functioning.<br><br>CONCLUSIONS: We found that an adapted CR intervention for Long COVID may improve post-COVID cognitive impairment in comparison to a time - and attention-matched control group and should be evaluated in a larger trial.<br><br>UNLABELLED: Trial registration: ClinicalTrials.gov identifier: NCT05498493. Registered on 08/10/2022.},
}
@article {pmid40991619,
year = {2025},
author = {Almeida, IDS and Ferreira, LGJ and Vaz, MA and Cipriano Junior, G and de Resende, MA and Vieira, DCL and Costa, RR and Babault, N and Marqueti, RC and Durigan, JLQ},
title = {Fatigue and neuromuscular function in long COVID: A one-year follow-up study.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0332242},
pmid = {40991619},
issn = {1932-6203},
mesh = {Humans ; Male ; *COVID-19/complications/physiopathology ; Female ; Middle Aged ; Adult ; Follow-Up Studies ; *Fatigue/physiopathology/etiology ; Longitudinal Studies ; SARS-CoV-2 ; Muscle Fatigue ; Muscle, Skeletal/physiopathology ; Brazil ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID has emerged as a significant complication of SARS-CoV-2 infection. However, the long-term neuromuscular consequences of this condition, particularly one-year post-infection, remain poorly understood. This study aimed to determine the mechanisms of fatigue by comparing perceived fatigue, objective fatigability, functionality, muscle architecture, and electrical neuromuscular function in participants who had suffered severe or moderate COVID‑19 one-year post-infection with a healthy control group.<br><br>METHODS AND FINDINGS: This longitudinal observational study followed participants for one-year. The assessments were conducted at the Laboratory of Muscle and Tendon Plasticity at the University of Bras&#xed;lia, Brazil. Participants who had suffered moderate or severe SARS-CoV-2 infection were compared to a control group. A baseline assessment was initially conducted (21-30 days post-symptoms onset or post-hospital discharge), followed by second (31-90), third (91-180), and fourth (181-360) assessments. Perceived fatigue, objective fatigability, functionality, muscle architecture, and electrical neuromuscular function were analyzed. The study included 30 controls (46.53 [42.10-51.43] years; 13 men [43.33%]), 22 moderate cases (38.27 [33.96-43.13] years; 10 men [45.45%]), and 18 severe cases (50.83 [45.19-57.18] years; eight men [44.44%]). Severe participants exhibited higher perceived fatigue in all assessments than the control group and at baseline and in assessment 4 compared to moderate cases, in addition to a lower torque and torque-time integral in all assessments of objective fatigability analysis compared to the other groups. The severe group also demonstrated reduced functionality, impaired muscle architecture (characterized by increased echogenicity), and higher chronaxie values in the electrical neuromuscular function assessment. Participants with moderate COVID&#x2011;19 exhibited alterations in perceived fatigue, reduced torque, and lower TTI, electrical neuromuscular function, and muscle architecture, particularly at baseline.<br><br>CONCLUSIONS: Severe participants continued to experience significant perceived fatigue even one-year post-infection, suggesting a slower recovery trajectory, that contributed to increased fatigability throughout the follow-up period. These results emphasize the role of musculoskeletal and neural mechanisms in post-COVID&#x2011;19 fatigue, highlighting the need for targeted, mechanism-based rehabilitation strategies.<br><br>TRIAL REGISTRATION: NCT04961255.},
}
@article {pmid40989546,
year = {2025},
author = {Cruz Neto, J and Fiuza Olivindo, CV and Guimarães Dos Santos, JA and Araujo da Silva, MA and de Oliveira Sales Junior, R},
title = {Cardiometabolic factors related to post-COVID-19 conditions: a scoping review.},
journal = {Revista Cuidarte},
volume = {16},
number = {2},
pages = {e4290},
pmid = {40989546},
issn = {2346-3414},
abstract = {INTRODUCTION: Post-COVID syndrome is a pathology that involves multiple sequelae. It is important to identify cardiometabolic risk factors as a way of preventing complications.<br><br>OBJECTIVE: To map the scientific evidence related to cardiometabolic factors in long post-COVID-19 conditions.<br><br>MATERIALS AND METHODS: Scoping review with the guiding question: What scientific evidence relates cardiometabolic factors to patients with long post-Covid-19 syndrome? The sources of information used were six databases via the CAPES journal portal. For the gray literature, we used the CAPES catalog of theses and dissertations, the Brazilian Digital Library of Theses and Dissertations, the Who Library Database and the medRxiv and OpenGrey repositories. The following descriptors were used: Adult, heart disease risk factors, Syndrome, SARS-CoV-2 and Covid 19 crossed using the Boolean operators AND and OR.<br><br>RESULTS: 14 studies were included. The cardiometabolic factors found were: abnormal levels of triglycerides, glycated hemoglobin, ferritin, inflammatory processes, decreased platelets, phospholipids and endothelial cells, oxidative stress, higher concentrations of monosaccharides and reduced polysaccharides, increased LDL, ALT, AST and bilirubin, with reduced GFR.<br><br>DISCUSSION: Patients with long-term COVID report persistent and debilitating symptoms that affect recovery, quality of life, economic and social activities. In addition to increased resting heart rate, tachycardia, palpitations, hypotension, syncope, orthostatic tachycardia, angina and heart attack.<br><br>CONCLUSION: Cardiometabolic factors expose the vulnerability of individuals affected by long Covid-19, so strategies are needed to reduce the systemic inflammatory impact of the disease and its clinical consequences.},
}
@article {pmid40987251,
year = {2025},
author = {Zhang, Y and Jiang, C and Jiang, W and Yuan, Y and Cao, D and Yuan, Y},
title = {Development and clinimetric validation of the Brief Brain Fog Scale (BBFS) for post-COVID cognitive symptoms.},
journal = {Journal of psychosomatic research},
volume = {198},
number = {},
pages = {112380},
doi = {10.1016/j.jpsychores.2025.112380},
pmid = {40987251},
issn = {1879-1360},
mesh = {Humans ; Female ; Male ; *COVID-19/complications/psychology ; Reproducibility of Results ; Middle Aged ; Psychometrics/instrumentation ; Adult ; Cross-Sectional Studies ; *Cognitive Dysfunction/diagnosis/etiology ; Aged ; Self Report ; Young Adult ; SARS-CoV-2 ; },
abstract = {OBJECTIVES: To develop and clinimetrically validate the Brief Brain Fog Scale (BBFS), a concise self-report tool for assessing post-COVID-19 cognitive symptoms, and to evaluate its structural validity, reliability and precision.<br><br>METHODS: The BBFS was generated from literature and expert review and finalized as five items targeting core brain-fog symptoms.A total of 844 participants completed an online cross-sectional survey, including 686 with self-reported post-COVID brain fog and 158 healthy controls. Rasch modeling and Mokken scaling were used to examine unidimensionality, item fit, person reliability, and item scalability. Local independence and differential item functioning (DIF) were assessed across age, sex, and education groups.<br><br>RESULTS: The BBFS fit Rasch model expectations (&#x3c7;[2]&#xa0;=&#xa0;44.6, df&#xa0;=&#xa0;60, p&#xa0;=&#xa0;0.928) and showed strong scalability (Mokken H&#xa0;=&#xa0;0.679). Reliability was high (PSI&#xa0;=&#xa0;0.846; WLE reliability&#xa0;=&#xa0;0.846; EAP reliability&#xa0;=&#xa0;0.852), with optimal precision in the moderate symptom range. All items had acceptable Infit MNSQ values (0.5-1.5), though several exhibited elevated Outfit in the highest response category. Local independence was largely supported; one pair marginally exceeded the indicative Q3[&#x204e;] threshold (0.204), and none exceeded 0.30. Uniform DIF was identified across age, sex, and education. Two items showed lower thresholds in older respondents, two showed higher thresholds in females, and four showed lower thresholds in postgraduate respondents. 'Forgetful' did not exhibit education-related DIF.<br><br>CONCLUSIONS: The BBFS is a reliable, unidimensional instrument for post-COVID brain fog, with robust measurement properties supported by Rasch and Mokken analyses. Although some items showed demographic sensitivity, the total scale functioned consistently across groups. The BBFS represents a potentially valid and practical screening instrument. Future work should examine longitudinal responsiveness, cross-cultural generalizability, and item refinements.},
}
@article {pmid40986436,
year = {2025},
author = {Santos, GA and Laranjeira, C and Carreira, L and Baldissera, VDA and Tostes, MFDP and Meireles, VC and Ageno, RS and Salci, MA},
title = {Living With Persistent Respiratory Symptoms of Long COVID: Qualitative Study Among Brazilian Adults 12 Months After Acute Infection.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70409},
pmid = {40986436},
issn = {1369-7625},
support = {//This study was financed in part by the Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior-Brasil (CAPES)-Finance Code 001 and Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)-Processo no. 402,882/2020-2. It was also supported by FCT-Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia, I.P. (UID/05704/2023) and by the Scientific Employment Stimulus-Institutional Call -[https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 25 July 2025]./ ; },
mesh = {Humans ; Brazil/epidemiology ; Female ; *COVID-19/complications/psychology/physiopathology ; Male ; Adult ; Qualitative Research ; Middle Aged ; SARS-CoV-2 ; Grounded Theory ; Post-Acute COVID-19 Syndrome ; Interviews as Topic ; Dyspnea/etiology ; },
abstract = {INTRODUCTION: The majority of those infected with COVID-19 undergo a brief duration of clinical illness. In certain instances, symptoms endure for months or years after the initial viral exposure-a condition characterized as Long COVID (LC). The experience of this illness remains largely unexplored as it has only recently surfaced. This study aims to understand the repercussions of persistent respiratory post-COVID symptoms in Brazilian adults 12 months after SARS-CoV-2 infection.<br><br>METHODS: A constructivist grounded theory study was employed. Data were collected through individual interviews with adults with persistent respiratory symptoms of Long COVID in Brazil. Data collection took place between September 2023 and February 2024. Data analysis was performed on a constant comparative basis and concurrent with data collection to understand the findings.<br><br>RESULTS: Twenty-four individuals (12 females, 12 males) with a median age of 43.29&#x2009;&#xb1;&#x2009;9.09 years participated. The data analysis generated a central category-living with the long-term effects of COVID-19: breathlessness pervades everything-around which three categories emerged: (1) imbalance between life before and after being infected by COVID-19; (2) living with acute post-COVID respiratory symptoms; and (3) struggling with persistent post-COVID respiratory symptoms.<br><br>CONCLUSION: Our analysis of the perceived needs of individuals with Long COVID underscores the urgent necessity for legislative reform to acknowledge LC as a disability that requires clear diagnostic criteria. Approaches to treatment and rehabilitation are required to evaluate the extent to which functioning and disability improve. Lastly, this study highlights the complex problems encountered by individuals with Long COVID, including employment uncertainties, everyday tasks and social relationships.},
}
@article {pmid40985761,
year = {2025},
author = {Hang Lam, IC and Zhou, J and Liu, W and Cheung Man, KK and Zhang, Q and Luo, H and Ho Wong, CK and Ling Chui, CS and Tsun Lai, FT and Li, X and Yin Chan, EW and Kei Wong, IC and Fai Wan, EY},
title = {Development and validation of age-specific predictive model on the risk of post-acute mortality within one year of COVID-19 infection.},
journal = {QJM : monthly journal of the Association of Physicians},
volume = {},
number = {},
pages = {},
doi = {10.1093/qjmed/hcaf218},
pmid = {40985761},
issn = {1460-2393},
abstract = {BACKGROUND: The existing risk prediction models for COVID-19 associated mortality have not considered the difference in risk factors in patients across an aging population.<br><br>AIM: To develop age-specific prediction models to forecast the risk of all-cause mortality in patients recovering from COVID-19 infection.<br><br>DESIGN: Population-based, retrospective cohort study.<br><br>METHODS: Patients with COVID-19 between 1 April 2020 and 31 July 2022 survived beyond the acute phase of infection were stratified into separate age cohorts (<45, 45-64, &#x2265;65) and followed-up for one year. Backward stepwise logistic regression and four statistical and machine learning algorithms were employed to develop age-specific models on the risk of post-acute mortality following COVID-19 infection, based on a comprehensive set of clinical parameters including demographics, COVID-19 vaccination status, pre-existing comorbidities and laboratory-test findings.<br><br>RESULTS: Of the 891,246 patients with COVID-19 identified, 13,578 (1.05%) died within one year of the index date. Age, COVID-19 vaccination status and history of acute respiratory syndrome prior infection were identified as predictors in the models for separate age groups. The model for patients aged &#x2265;65 exhibited excellent prediction performance with an AUROC of 0.87 (95% CI: 0.87, 0.88), followed by the model for patients aged 45-64 [AUROC=0.83 (95% CI: 0.81, 0.85)] and those aged <45 [AUROC=0.79 (95% CI: 0.72, 0.86)].<br><br>CONCLUSION: The age-specific models reported accurately predicted the risk of post-acute mortality in their corresponding age-group of patients, providing valuable asset in optimising clinical strategies and resource allocation in the management of the global burden of Long COVID.},
}
@article {pmid40984162,
year = {2025},
author = {Flattum-Riemers, T and Susi, A and Nylund, C},
title = {Incidence Trends and Co-Diagnosis of Post-COVID-19 Condition in the Active Duty Population.},
journal = {Military medicine},
volume = {190},
number = {Supplement_2},
pages = {599-604},
doi = {10.1093/milmed/usaf283},
pmid = {40984162},
issn = {1930-613X},
support = {//intramural Uniformed Services University of Health Sciences/ ; //Department of Defense High Priority Award/ ; },
mesh = {Humans ; Incidence ; *COVID-19/epidemiology/complications ; *Military Personnel/statistics &amp; numerical data ; Female ; Male ; Adult ; Cross-Sectional Studies ; Middle Aged ; United States/epidemiology ; Adolescent ; },
abstract = {INTRODUCTION: Long COVID, also known as Post-COVID-19 Condition (PCC) is characterized by the persistence or development of symptoms following SARS-CoV-2 infection. Post-COVID-19 Condition has the potential to impact military readiness, and yet the incidence among active duty service members (ADSM) is unknown. The objective of this study is to assess the incidence of diagnosed PCC, explore demographic associations, and identify common co-occurring diagnoses among ADSM.<br><br>MATERIALS AND METHODS: We conducted a repeated cross-sectional study using the Military Health System Data Repository (MDR). The MDR was queried for care records containing the ICD-10 code for PCC, U09.9, from October 2021 to October 2022. Incidence was calculated using the monthly counts, although Incidence Rate Ratios were calculated using a Poisson regression model, adjusting for age, sex, rank, race/ethnicity, and region. The frequency of co-occurring diagnoses with PCC encounters was analyzed to identify the top co-occurring diagnoses.<br><br>RESULTS: A total of 7,171 ADSM were diagnosed with PCC. The average monthly incidence of PCC was 4.7 per 10,000 ADSM. Females had 3.70 times (95% CI, 3.50-3.90) the adjusted incident rate ratio (aIRR) of PCC compared to males. Active duty service members aged 55-64 had the greatest risk with an aIRR of 28.81 (95% CI, 20.81-38.75) compared to ADSM aged 17-24. The highest frequency co-occurring diagnoses were respiratory signs and symptoms, with 874 diagnosed with R06.02 (shortness of breath).<br><br>CONCLUSION: Post-COVID-19 Condition represents a significant burden on the health of ADSM. Further research is warranted to study trends of PCC among the ADSM and to assess the effect of PCC on readiness and retention.},
}
@article {pmid40981264,
year = {2025},
author = {Pomroy, HJ and Mote, A and Mathew, S and Chanasseril, S and Lu, V and Cheema, AK},
title = {From Fork to Brain: The Role of AGE-RAGE Signaling and the Western Diet in Neurodegenerative Disease.},
journal = {NeuroSci},
volume = {6},
number = {3},
pages = {},
pmid = {40981264},
issn = {2673-4087},
abstract = {Advanced glycation end products (AGEs) are reactive compounds formed through non-enzymatic glycation in a process known as the Maillard reaction. While humans produce AGEs endogenously, these compounds can also enter the body through dietary sources, food preparation methods, and exposure to agricultural and food-related chemicals. AGEs can accumulate within cells and impair cellular function. In addition, when AGEs bind to receptors for advanced glycation end products (RAGE), they activate intracellular signaling pathways that promote the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. Sustained AGE-RAGE signaling drives chronic inflammation contributing to the development of various ailments, including neurodegenerative diseases. This review examines AGE formation, metabolism, and accumulation, with an emphasis on dietary sources as modifiable contributors to AGE-RAGE mediated pathology. We highlight the need for further research on dietary AGE restriction as a potential strategy to prevent or slow the progression of neurodegenerative and neuroinflammatory disorders.},
}
@article {pmid40981197,
year = {2025},
author = {Matangkha, K and Punyahotara, V and Rintra, J and Sittiprapaporn, P},
title = {Association Between Vitamin D Levels and Long COVID Signs and Symptoms.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
pmid = {40981197},
issn = {2076-3271},
mesh = {Humans ; *COVID-19/blood/epidemiology/complications ; Female ; Male ; Adult ; *Vitamin D/blood/analogs &amp; derivatives ; Middle Aged ; SARS-CoV-2 ; Young Adult ; *Vitamin D Deficiency/blood/epidemiology ; Adolescent ; Prevalence ; },
abstract = {BACKGROUND: "Long COVID" refers to a condition in which individuals continue to experience persistent signs and symptoms even after recovering from the initial COVID-19 infection. Signs and symptoms that persist can affect multiple organs in the body. Vitamin D is an essential nutrient that plays a crucial role, particularly in the immune system, and may be linked to the development of long COVID.<br><br>OBJECTIVE: The study aimed to investigate the association between vitamin D levels and the prevalence of long COVID signs and symptoms in COVID-19 patients.<br><br>MATERIALS AND METHODS: The study enrolled 170 COVID-19 patients with mild signs and symptoms and confirmed COVID-Ag or RT-PCR tests. The subjects were aged 18-59 years. All patients had 25(OH)D levels measured within 60 days of COVID-19 diagnosis and had been followed for at least 3 months post-infection. Data collected included demographic characteristics, serum 25(OH)D levels, and self-reported long COVID signs and symptoms questionnaire responses.<br><br>RESULTS: The study results indicated a female-to-male ratio of 1.1:1 and a mean age of 45.87 &#xb1; 8.65 years; of these, 62.4% received three doses of the COVID-19 vaccine, and 64.7% developed long COVID. The most prevalent signs and symptoms were respiratory (55.3%), skin (50.6%), and general (39.4%). The median blood vitamin D level was 22.96 ng/mL, with 41.2% of subjects having insufficient levels, 30.6% having deficient levels, and 28.2% having sufficient levels. Patients with long COVID had significantly lower vitamin D levels compared with those without long COVID (21.52 ng/mL vs. 25.46 ng/mL; p < 0.05). Multivariable analysis found that vitamin D deficiency was significantly associated with overall long COVID signs and symptoms (Adj. OR, 5.80 [95% CI: 2.10, 16.13]). Additionally, vitamin D deficiency significantly increased the number of long COVID systemic signs and symptoms (Adj. IRR, 3.30 [2.12, 5.12]).<br><br>CONCLUSION: Assessing and maintaining vitamin D levels, vitamin D supplementation, and sunlight exposure in COVID-19 patients can reduce the risk and severity of long-term COVID-19 signs and symptoms.},
}
@article {pmid40980765,
year = {2025},
author = {Xiong, R},
title = {Advancing Digital Precision Medicine for Chronic Fatigue Syndrome through Longitudinal Large-Scale Multi-Modal Biological Omics Modeling with Machine Learning and Artificial Intelligence.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {40980765},
issn = {2331-8422},
support = {U54 NS105539/NS/NINDS NIH HHS/United States ; },
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex debilitating disorder manifesting as severe fatigue and post-exertional malaise. The etiology of ME/CFS remains elusive. Here in chapter one, we present a deep metagenomic analysis of stool combined with plasma metabolomics and clinical phenotyping of two ME/CFS cohorts with short (<4y, n=75) or long-term disease (>10y, n=79) compared to healthy controls (n=79). First, we describe microbial and metabolomic dysbiosis in ME/CFS patients. Short-term patients showed significant microbial dysbiosis, while long-term patients had largely resolved microbial dysbiosis but had metabolic and clinical aberrations. Second, we identified phenotypic, microbial, and metabolic biomarkers specific to patient cohorts. These revealed potential functional mechanisms underlying disease onset and duration, including reduced microbial butyrate biosynthesis together with a reduction in plasma butyrate, bile acids, and benzoate. In addition to the insights derived, our data represent an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS. We then studied a more generalized question in chapter two: chronic diseases like ME/CFS and long COVID exhibit high heterogeneity with multifactorial etiology and progression, complicating diagnosis and treatment. To address this, we developed BioMapAI, an explainable Deep Learning framework using the richest longitudinal multi- 'omics dataset for ME/CFS to date. This dataset includes gut metagenomics, plasma metabolome, immune profiling, blood labs, and clinical symptoms. By connecting multi- 'omics to a symptom matrix, BioMapAI identified both disease- and symptom-specific biomarkers, reconstructed symptoms, and achieved state-of-the-art precision in disease classification. We also created the first connectivity map of these 'omics in both healthy and disease states and revealed how microbiome-immune-metabolome crosstalk shifted from healthy to ME/CFS. Thus, we proposed several innovative mechanistic hypotheses for ME/CFS: Disrupted microbial functions - SCFA (butyrate), BCAA (amino acid), tryptophan, benzoate - lost connection with plasma lipids and bile acids, and activated inflammatory and mucosal immune cells (MAIT, γ δ ⊤ cells) with INFγ and GzA secretion. These abnormal dynamics are linked to key disease symptoms, including gastrointestinal issues, fatigue, and sleep problems.},
}
@article {pmid40980657,
year = {2025},
author = {Ribeiro, HS and Frediani, MM and Marçal, L and Antonângelo, L and Catharina, GS and Yu, L and Zanetta, DMT and Mauad, T and Moreira, TCL and Gouveia, N and Busatto, GF and Carvalho, CRR and Burdmann, EA and , },
title = {Community-Acquired Acute Kidney Injury and Late Kidney Dysfunction in Survivors of COVID-19 Hospitalization.},
journal = {Kidney international reports},
volume = {10},
number = {9},
pages = {3032-3043},
pmid = {40980657},
issn = {2468-0249},
abstract = {INTRODUCTION: Data on the incidence and risk factors for renal long COVID are scarce. We aimed to investigate 2 acute kidney injury (AKI) phenotypes, namely community-acquired (CA; CA-AKI) and hospital-acquired (HA; HA-AKI), and the development of late kidney dysfunction in survivors of COVID-19 hospitalization.<br><br>METHODS: This is a prospective cohort study of survivors of moderate-to-severe COVID-19 hospitalization in Brazil, from March to August 2020. The patients were assessed for up to 11 months after hospital discharge. Exposure was CA-AKI and HA-AKI. The main outcome was kidney dysfunction defined as incident low estimated glomerular filtration rate (eGFR; < 60 ml/min per 1.73 m[2]) and/or eGFR decline &#x2265; 25% from discharge at follow-up. An adjusted binary logistic regression analysis was run.<br><br>RESULTS: A total of 655 survivors were evaluated (6.5 &#xb1; 1.9 follow-up months); 79% had AKI (35% CA and 43% HA); 14% used kidney replacement therapy (KRT). Late kidney dysfunction occurred in 28% of the patients (16% with incident low eGFR and 27% with eGFR decline &#x2265; 25%). CA-AKI, but not HA-AKI, was independently associated with late kidney dysfunction (adjusted odds ratio [aOR] = 7.3, 95% confidence interval (CI): 3.6-15.8 and aOR = 2.2, 95% CI: 0.9-4.8, respectively).<br><br>CONCLUSION: In conclusion, late kidney dysfunction affected 1 in 4 COVID-19 survivors. CA-AKI, but not HA-AKI, was an independent risk factor for late kidney dysfunction. These findings suggest that renal long COVID might be frequent and that a specific AKI phenotype (CA-AKI) may play a crucial role in its development. Our research highlights the need for CA-AKI prevention and for the long-term follow-up and care of patients affected by this AKI phenotype during COVID-19 infection.},
}
@article {pmid40980513,
year = {2025},
author = {Pettemeridou, E and Loizidou, M and Trajkovic, J and Constantinou, M and De Smet, S and Baeken, C and Sack, AT and Williams, SCR and Constantinidou, F},
title = {Cognitive and Psychological Symptoms in Post-COVID-19 Condition: A Systematic Review of Structural and Functional Neuroimaging, Neurophysiology, and Intervention Studies.},
journal = {Archives of rehabilitation research and clinical translation},
volume = {7},
number = {3},
pages = {100461},
pmid = {40980513},
issn = {2590-1095},
abstract = {OBJECTIVE: To investigate the structural, functional, and neurophysiological brain changes associated with post-COVID-19 condition (PCC)-related cognitive and psychological issues and evaluate the efficacy of noninvasive brain stimulation (NIBS) and cognitive rehabilitation interventions.<br><br>DATA SOURCES: Electronic databases, including Web of Science, PubMed, and Embase, were systematically searched for articles published before February 1, 2025, using terms such as "post-COVID-19 condition," "cognitive dysfunction," "brain changes," "noninvasive brain stimulation," and "cognitive rehabilitation." Language was restricted to English, and only studies involving human participants were included.<br><br>STUDY SELECTION: Studies with human participants aged &#x2265;18 years diagnosed with PCC, employing magnetic resonance imaging, functional magnetic resonance imaging, positron emission tomography, and electroencephalography, and interventions such as NIBS and cognitive rehabilitation were included. Articles were selected through independent review by multiple authors, with consensus resolving discrepancies. Of the 123 studies initially identified, 78 met the inclusion criteria.<br><br>DATA EXTRACTION: Data on participant demographics, methodologies, neurophysiological changes, and intervention outcomes were extracted by 2 independent reviewers using predefined guidelines. Study quality was assessed using the Newcastle-Ottawa Scale and Critical Appraisal Skills Program tools.<br><br>DATA SYNTHESIS: Seventy-eight studies with over 5900 participants met the inclusion criteria. Significant cognitive impairments were observed in attention, executive function, and memory (N=78). Key findings included mixed evidence of gray matter (N=16) and white matter volume changes (N=20), cortical thickness alterations (N=9), variations in functional connectivity (N=14), electrophysiology (N=9), and blood flow (N=8). NIBS, including transcranial magnetic stimulation (N=8) and transcranial direct current stimulation (N=2), showed potential benefits for managing depression and cognitive impairments. Although cognitive rehabilitation (N=3) showed promise, it requires further investigation.<br><br>CONCLUSIONS: This review highlights the complex neurologic underpinnings of PCC and the potential of NIBS and cognitive rehabilitation as interventions. Further research is essential to refine these interventions and establish evidence-based strategies for addressing long-term cognitive and psychological effects of PCC.},
}
@article {pmid40979552,
year = {2025},
author = {Adebisi, YA and Alhur, AA and Alshahrani, NZ and Cañezo, VC and Cue, EG and Lucero-Prisno, DE},
title = {Pre-pandemic diabetes and risk of long COVID: longitudinal evidence.},
journal = {Journal of diabetes and metabolic disorders},
volume = {24},
number = {2},
pages = {207},
pmid = {40979552},
issn = {2251-6581},
abstract = {OBJECTIVE: To examine whether pre-pandemic diabetes is associated with an increased risk of Long COVID in a nationally representative UK cohort.<br><br>METHODS: We conducted a prospective cohort analysis using data from the UK Household Longitudinal Study. A total of 11,669 adults aged&#x2009;&#x2265;&#x2009;16 years were followed from Wave 10 (2018-19) to Wave 14 (2022-23). The primary exposure, pre-pandemic diabetes, was defined at baseline (Wave 10) based on self-report of a doctor diagnosis. The primary outcome, Long COVID, was assessed at follow-up (Wave 14) and defined as self-reported symptoms lasting more than 12 weeks after a COVID-19 infection that could not be explained by another cause. Modified Poisson regression models with robust standard errors were used to estimate relative risks of Long COVID associated with pre-pandemic diabetes. Predictive margins were then calculated to obtain adjusted probabilities.<br><br>RESULTS: At follow-up, 1,076 participants (9.2%) reported Long COVID. In the unadjusted model, participants with pre-pandemic diabetes had a 36% higher risk of Long COVID compared with those without diabetes (RR&#x2009;=&#x2009;1.36, 95% CI: 1.09-1.69, p&#x2009;=&#x2009;0.006). After adjusting for age and sex, the relative risk increased to 1.43 (95% CI: 1.15-1.79, p&#x2009;=&#x2009;0.002). In the fully adjusted model, which controlled for age, sex, ethnicity, education, income satisfaction, smoking, and other long-standing illness, the relative risk of Long COVID in participants with diabetes was 1.60 (95% CI: 1.27-2.02, p&#x2009;<&#x2009;0.001). The adjusted predicted probability of long COVID was 14.4% (95% CI: 11.2-17.6) among those with diabetes, compared with 9.0% (95% CI: 8.5-9.5) among those without.<br><br>CONCLUSIONS: In this nationally representative prospective cohort, pre-pandemic diabetes emerged as an independent risk factor for Long COVID. Enhanced surveillance and targeted support for individuals with diabetes may be warranted in Long COVID care strategies.},
}
@article {pmid40979084,
year = {2025},
author = {Kent, DA and Villegas-Downs, M and Wilson, A and Krishnan, J and Gerald, L},
title = {Navigating the challenges of NT-proBNP result disclosure in clinical research.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e176},
pmid = {40979084},
issn = {2059-8661},
abstract = {BACKGROUND: The Office of Human Research Protections and the National Academy of Sciences, Engineering, and Medicine (NASEM) recommend the return of individual research results (IRRs) to study participants as a strategy to build public trust in science. However, the feasibility of sharing IRRs is unclear. Within a National Institutes of Health (NIH) funded parent study about Long COVID, we embedded the My ILLInet RECOVER Return of Results study to explore clinician-level considerations (e.g., validity, actionability, recommendations for follow-up) about returning a clinically used biomarker for heart failure (N-terminal pro-B-type natriuretic peptide, (NT-proBNP) collected as part of the NIH RECOVER study protocol.<br><br>APPROACH: Clinicians participated in a three-phase modified Delphi process that sought their input to guide appropriate follow up recommendations the research team should provide to research participants with an abnormal NT-proBNP.<br><br>RESULTS: Clinicians agreed that NT-proBNP results could be returned to study participants. However, consensus was not reached on specific NT-proBNP thresholds that warrant immediate medical attention versus general follow-up.<br><br>DISCUSSION: Lack of clinical context presents a challenge in returning IRRs. Clinicians expressed concerns about the potential harm caused by misinformation or misinterpretation of these findings. While the NASEM report offers guidance on communicating IRRs, careful consideration is essential to ensure that clinical uncertainty is conveyed clearly, minimizing the risk of misinterpretation.<br><br>CONCLUSION: The feasibility of returning IRRs to study participants depends, in part, on sufficient clinical context for the information to be actionable.},
}
@article {pmid40978825,
year = {2025},
author = {Kouyoumdjian, JA and Yamamoto, LA and Graca, CR},
title = {Exploration of Intersections and Divergences of Long COVID and Chronic Fatigue Syndrome.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e90607},
pmid = {40978825},
issn = {2168-8184},
abstract = {BACKGROUND: Fatigue is the most common symptom of Long COVID (LC), defined by persistent or newly emerging symptoms that develop at least three months after an initial SARS-CoV-2 infection, in the absence of other identifiable cause. This study investigates the prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as a potential comorbidity of LC.<br><br>METHODS: &#xa0;The study enrolled 37 adult controls with no documented SARS-CoV-2 infection and 32 individuals&#xa0;with a history of infection, categorized as&#xa0;LC-yes (with LC symptoms) and LC-no (without LC symptoms).&#xa0;ME/CFS diagnosis was&#xa0;based on the&#xa0;International Consensus Criteria (ICC).<br><br>RESULTS: &#xa0;Among LC-yes cases, the most frequently reported symptoms included post-exertional malaise (PEM); neurosensory, perceptual, or motor disturbances; cognitive impairment; sleep disturbances; pain; impaired thermoregulation; and flu-like symptoms, all occurring significantly more than in the LC-no or control groups. All individuals in the LC-yes group reported PEM. ME/CFS was diagnosed in three LC-yes&#xa0;cases (18.8%), one LC-no case&#xa0;(6.7%), and four control subjects&#xa0;(10.8%), with no statistically significant differences observed among groups. Experiencing more than six symptoms during acute infection, such as fatigue, loss of taste or smell, headache, fever, cough, myalgia, sore throat, shortness of breath, rhinorrhea, and diarrhea, was associated with a twofold higher risk of developing LC.<br><br>CONCLUSION: A substantial proportion of LC-yes individuals experienced PEM; neurosensory, perceptual, or motor disturbances; cognitive impairment; and sleep disturbances, with rates significantly exceeding those in the LC-no and control groups. Nevertheless, only a minority of LC-yes cases (18.8%) satisfied criteria for the ME/CFS, and the prevalence did not significantly differ from LC-no and controls. These findings suggest that while many symptoms of LC overlap with those of ME/CFS, only a subset of LC cases meet established ME/CFS diagnostic criteria.},
}
@article {pmid40978720,
year = {2025},
author = {Wei, DJ and Chow, CW and Cheung, WYH and Yeung, WF and Cao, PH and Liong, C and Chen, HY and Zhang, S and Zhong, LLD},
title = {Electro-acupuncture for long COVID neuropsychiatric symptoms: study protocol for a prospective, randomized sham-controlled, patient-assessor-blinded clinical trial.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1620288},
pmid = {40978720},
issn = {2296-858X},
abstract = {INTRODUCTION: Patients recovering from long COVID often endure a spectrum of neuropsychiatric symptoms, including cognitive impairment, memory deficits, mood disturbances and sleep disorders, that significantly impact their quality of life. Acupuncture, particularly electroacupuncture, has shown promise in addressing these symptoms. Currently there is no high-quality clinical trial for acupuncture on long COVID neuropsychiatric symptoms.<br><br>METHODS AND ANALYSIS: In this 24 weeks, sham-controlled, patient-assessor-blinded randomized trial, 150 long COVID patients will be equally allocated to either an electroacupuncture group (EAG) or a sham control group (SCG). Each subject will receive a total of 32 intervention sessions over a 16 weeks intervention phase (two sessions each week) and will be followed up for an additional 8 weeks. Primary outcomes include changes in the Mini-Mental State Examination (MMSE) and the Chinese version of the Beck Depression Inventory (CBDI) scores. Secondary outcomes include the Insomnia Severity Index (ISI), Brief Fatigue Inventory-Taiwan (BFI-T), and the Short Form 12 (SF-12). All outcomes will be assessed at baseline and then at 4 weeks intervals during both the treatment and post-treatment periods.<br><br>DISCUSSION: This trial aims to generate robust clinical data on the therapeutic effects of electroacupuncture for long COVID. The anticipated results will clarify electroacupuncture's value as a therapeutic option for neuropsychiatric symptoms in long COVID patients, contributing to evidence-based practice in integrative medicine.},
}
@article {pmid40977575,
year = {2026},
author = {Ribeiro, A and Hadavi, S and Gall, N and Hadden, RDM and Serra, J},
title = {Microneurography Reveals Unmyelinated Small Nerve Fiber Dysfunction in Long COVID.},
journal = {Annals of neurology},
volume = {99},
number = {2},
pages = {356-368},
doi = {10.1002/ana.78045},
pmid = {40977575},
issn = {1531-8249},
mesh = {Humans ; Adult ; Female ; *COVID-19/physiopathology/complications ; Male ; Middle Aged ; Adolescent ; Young Adult ; *Nerve Fibers, Unmyelinated/physiology ; Neural Conduction/physiology ; Electrodiagnosis/methods ; SARS-CoV-2 ; *Small Fiber Neuropathy/physiopathology ; Nociceptors/physiology ; },
abstract = {OBJECTIVE: To review the microneurography findings of long coronavirus disease 2019 (COVID) patients who presented to the clinic with multisystem involvement affecting neurological, cardiovascular, gastrointestinal, genitourinary, pulmonary, and immunological domains.<br><br>METHODS: We analyzed 36 consecutive long COVID patients using microneurography. We evaluated abnormalities in C nociceptors, including spontaneous activity, peripheral sensitization, multiple spikes, conduction failure, and alterations in activity-dependent slowing of conduction velocity. Sympathetic nerve fiber function was assessed using the recovery cycle of excitability. Results were compared with a large normative database.<br><br>RESULTS: The mean age was 40.9&#x2009;&#xb1;&#x2009;9.2&#x2009;years (range 17-60&#x2009;years), with a female predominance (30/36, 83.3%). Patients were seen from 15 to 61&#x2009;months after onset of symptoms (35.7&#x2009;&#xb1;&#x2009;11.3&#x2009;months). All patients presented with neuropathic symptoms, mainly pain and orthostatic intolerance. A total of 32 patients (88.9%) had objective electrophysiological abnormalities in peripheral C fibers, including spontaneous nociceptor activity (61.1%), peripheral sensitization (27.8%), and multiple spikes (11.1%). Long COVID patients also showed a significant shift in C nociceptor populations, with a higher prevalence of type&#x2009;1B mechano-insensitive C&#x2009;nociceptors compared with healthy controls. Changes in activity-dependent slowing of conduction velocity differed in opposite directions between mechano-sensitive and mechano-insensitive C nociceptors. Postganglionic sympathetic fibers also showed abnormal recovery cycles with a lack of supernormality, suggesting impaired neuronal homeostasis.<br><br>INTERPRETATION: This study provides novel electrophysiological evidence linking small nerve fiber dysfunction to long COVID. These findings align with previous histological evidence of small nerve fiber loss, reinforcing the hypothesis that peripheral nerve dysfunction contributes to the multisystem symptoms of long COVID. ANN NEUROL 2026;99:356-368.},
}
@article {pmid40977216,
year = {2025},
author = {Hitch, D and Botha, T and Tesfay, F and Holton, S and Said, CM and Hensher, M and Richards, K and Angeles, MR and Bennett, CM and Pepin, G and Rasmussen, B and Nicola-Richmond, K},
title = {Impacts of long COVID on disability, function and quality of life for adults living in Australia.},
journal = {Australian journal of primary health},
volume = {31},
number = {},
pages = {},
doi = {10.1071/PY25033},
pmid = {40977216},
issn = {1836-7399},
mesh = {Humans ; *Quality of Life ; Male ; Australia/epidemiology ; Female ; *COVID-19/psychology/complications/epidemiology ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Persons with Disabilities/statistics &amp; numerical data/psychology ; Aged ; Activities of Daily Living ; Disability Evaluation ; SARS-CoV-2 ; Young Adult ; },
abstract = {Background To describe the impact of long COVID on disability, function and quality of life among adults living in Australia. Method People aged >18years with a history of COVID-19 infection confirmed by polymerase chain reaction or rapid antigen test were eligible for this cross-sectional survey. The World Health Organization Disability Assessment Schedule 2.0 measured disability and function, and the 36-Item Short Form Health Survey assessed quality of life. Results Participants (n =121) reported significant functional impairment and reduced quality of life compared with established population norms for these outcome measures. Most (n =104, 86%) reported clinically significant disability and participation limitations in daily activities. Mean World Health Organization Disability Assessment Schedule 2.0 scores indicated higher levels of disability than 98% of the general population. The 36-Item Short Form Health Survey scores indicated lower quality of life across all domains, but particularly in relation to vitality and social functioning. Regression analysis found significant associations between the World Health Organization Disability Assessment Schedule 2.0 and 36-Item Short Form Health Survey scores, and vaccine dose number, comorbidities and self-rated recovery. Conclusion Long COVID is associated with significantly reduced function and quality of life, which are distinct outcomes requiring targeted assessment and intervention. The overall impact may be exacerbated in people with pre-existing comorbidities who are more susceptible to long COVID in the first place. The findings underscore the need for targeted rehabilitation and support services for people living in Australia with long COVID, and further longitudinal research to explore the long-term impact on disability and quality of life, and inform policy and healthcare service delivery.},
}
@article {pmid40976237,
year = {2025},
author = {Soria, B and Andreu, E and Gonzaga, A},
title = {Long COVID: Is mitochondria the target?.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {33},
number = {10},
pages = {4696-4698},
pmid = {40976237},
issn = {1525-0024},
}
@article {pmid40975587,
year = {2025},
author = {Sinha, SS and Bari, S and Tripathi, P and Kant, S and Tripathi, SM},
title = {Neuropsychiatric manifestations of long COVID.},
journal = {The Indian journal of tuberculosis},
volume = {72},
number = {4},
pages = {532-536},
doi = {10.1016/j.ijtb.2025.02.020},
pmid = {40975587},
issn = {0019-5707},
mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Mental Disorders/etiology ; *Nervous System Diseases/etiology ; },
abstract = {In 2019 after the COVID-19 outbreak, a subset of patients was observed to be experiencing unusual symptoms and prolonged illness following SARS-CoV-2 infection and were labeled as "Long-haulers". Various terms like Long COVID, and Post-COVID-19 Conditions (PCC) were used to describe symptoms extending four weeks or more. Long COVID encompasses a range of persistent symptoms with a multisystemic nature, exhibiting a relapsing-remitting pattern. Various theories explaining Long COVID such as direct neuro-invasion, systemic effects of the virus, and neuroimmune dysregulation have been suggested. Clinical manifestations of Long COVID include diverse symptoms with fatigue, dyspnea, and cognitive impairment being common symptoms reported. Neurological manifestations are more prevalent in severe COVID-19 cases. Non-specific neurological manifestations include loss of taste and smell while specific neurological manifestations include hemiplegia and large artery ischemic stroke. COVID-19 medications may also cause neurological symptoms. Psychiatric manifestations include depression, anxiety, panic disorders, post-traumatic stress disorder (PTSD), psychosis, and cognitive symptoms such as attention and executive function deficits. Psychological symptoms vary among different social groups like frontline health workers, young individuals, and the elderly. Social isolation exerts a substantial impact on the psychological presentations of Long COVID through mechanisms such as Hypothalamic-Pituitary-Adrenal axis (HPA) hyperactivation, epigenetic modifications, increased steroid concentrations, immune system suppression, and reactivation of latent infections. Conclusively, neuroimmune dysregulation, social isolation and associated factors serve as the link between SARS-CoV-2 virus, long COVID and its neuropsychiatric manifestations.},
}
@article {pmid40973114,
year = {2025},
author = {Vassiliou, VS and Tsampasian, V and Luchian, ML and D'Ascenzi, F and D'Ascenzo, F and Dweck, MR and Escaned, J and Gati, S and Halle, M and Koskinas, KC and Neubeck, L and Papadakis, M and Petersen, SE and Ristic, A and Metra, M and Biondi-Zoccai, G},
title = {Cardiovascular disease prevention and management in COVID-19: a clinical consensus statement of the European Association of Preventive Cardiology, the European Association of Cardiovascular Imaging, the Association of Cardiovascular Nursing &amp; Allied Professions, the European Association of Percutaneous Cardiovascular Interventions, and the Heart Failure Association of the ESC.},
journal = {European journal of preventive cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/eurjpc/zwaf540},
pmid = {40973114},
issn = {2047-4881},
abstract = {The coronavirus-associated disease 2019 (COVID-19) pandemic has posed significant challenges due to the complex interplay between SARS-CoV-2 infection and cardiovascular disease. COVID-19 can trigger and exacerbate cardiovascular complications, observed both during the acute phase of infection and in the post-acute phase, with some individuals developing long-term sequelae collectively termed Long COVID. Additionally, reinfection and adverse reactions to COVID-19 vaccines may contribute to cardiovascular events. This clinical consensus statement, developed by associations of the European Society of Cardiology, aims to provide a comprehensive overview of cardiovascular prevention strategies across all stages of COVID-19. These include addressing cardiovascular risk associated with acute infection, prior infection, Long COVID, reinfection, and post-vaccination events. Key recommendations focus on preventing and managing cardiovascular manifestations in patients with acute or prior COVID-19, implementing targeted cardiovascular rehabilitation, and introducing interventions to mitigate the severity of Long COVID. The document also emphasizes lifestyle modifications and personalized therapeutic approaches to enhance patient outcomes. Given the evolving nature of COVID-19 and its long-term cardiovascular implications, ongoing research is crucial to address existing knowledge gaps, optimize preventive strategies, and improve patient care. Future studies should prioritize the individualization of preventive measures for diverse populations, refine rehabilitation strategies, and advance long-term cardiovascular care, ensuring that evidence-based practices continue to evolve alongside emerging data.},
}
@article {pmid40971997,
year = {2025},
author = {Ibrahim, A and Cesari, M and Tang, Q and Aktan Süzgün, M and Brandauer, E and Holzknecht, E and Wachter, A and Anselmi, V and Heidbreder, A and Stefani, A and Högl, B},
title = {Sleep Architecture and REM Sleep Without Atonia in Post-COVID-19 Insomnia.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf257},
pmid = {40971997},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: Insomnia associated with COVID-19 infection is a common complaint in long-COVID. Studies to date have predominantly examined post-COVID-19 sleep disturbances with questionnaires. We aimed to investigate whether there are distinctive polysomnographic findings in post-COVID-19 insomnia compared to non-COVID-related chronic insomnia.<br><br>METHODS: We included 150 patients with chronic insomnia, stratified into three groups: post-COVID-19 insomnia (n&#x2009;=&#x2009;50), chronic insomnia during the pandemic without a history of COVID-19 infection (n&#x2009;=&#x2009;50), and pre-pandemic chronic insomnia (n&#x2009;=&#x2009;50). All patients underwent one-night video-polysomnography (v-PSG). The sleep architecture, respiratory variables and REM sleep without atonia (RWA) were compared across the groups.<br><br>RESULTS: Classical polysomnographic variables showed no significant differences across groups with regard to total sleep time, sleep efficiency, sleep stage percentages, and the apnea-hypopnea index. Post-COVID-19 insomnia patients had significantly increased RWA at both the chin and the flexor digitorum superficialis (FDS) (p=.020 for both), and higher nocturnal heart rates (p=.046). Sleep-bout analysis indicated shorter sustained N3-sleep periods (p=.001) and longer onset to stable REM-sleep (p=.016) in the post-COVID-19 insomnia group. Although sleep transitions did not withstand multiple comparison corrections, they revealed a trend towards decreased N3-sleep continuity and increased probabilities of transitioning to lighter stages (N3&#xa0;&#x2192;&#xa0;N3: unadjusted-p=.012; REM&#xa0;&#x2192;&#xa0;N1: unadjusted-p=.027) in the post-COVID-19 insomnia.<br><br>CONCLUSIONS: Classical PSG profile of post-COVID-19 insomnia does not differ from non-COVID-related chronic insomnia. However, subtle differences in RWA and sleep integrity suggest that post-COVID-19 insomnia is driven not merely by pandemic-related stress factors but by additional physiological alterations linked to viral CNS involvement.},
}
@article {pmid40966577,
year = {2025},
author = {León-Herrera, S and Gómez-Bravo, R and Sánchez-Castro, M and Pavlou, MAS and Fischer, VJ and Hutmacher, D and Haeck, L and Weber, N and Oliván-Blázquez, B and Magallón-Botaya, R and Benoy, C and Schneider, JG},
title = {Fasting and Caloric Restriction in Long COVID Syndrome: A Scoping Review of Interventions and Outcomes.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuaf141},
pmid = {40966577},
issn = {1753-4887},
support = {//FASTCOV/ ; //Ministry of Health and Social Security of Luxembourg/ ; },
abstract = {BACKGROUND: Since the emergence of COVID-19, many patients continue to experience symptoms beyond the acute phase, a condition now termed long COVID syndrome (LCS). The complexity of LCS, with its varied symptoms, makes diagnosis and treatment challenging. Recent evidence suggests that dietary approaches, such as fasting and caloric restriction, may help in management of these symptoms. However, research on these interventions remains limited and preliminary.<br><br>OBJECTIVES: In this review we aimed to explore existing studies on the impacts of fasting and caloric restriction for LCS management, focusing on how these approaches might alleviate symptoms through mechanisms like reduced inflammation, enhanced autophagy, and better metabolic health. Additionally, we examined intervention types, reported outcomes, and gaps in the research to guide future studies of LCS.<br><br>METHODS: A systematic search was conducted using databases like PubMed, Scopus, and ScienceDirect for studies published from 2019 to 2024, following the Arksey and O'Malley framework and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A range of study types, including case series, narrative reviews, randomized controlled trial protocols, and public guidance documents, were included. Data were descriptively compiled.<br><br>RESULTS: Eleven studies met inclusion criteria, covering interventions such as intermittent and prolonged fasting, as well as caloric restriction, with durations from days to weeks. Some reported benefits included reductions in fatigue, cognitive impairment, and inflammatory symptoms such as joint pain, muscle pain, or chest tightness. However, the findings reported here are preliminary and limited by small sample sizes, short follow-up, and varied protocols and outcomes, underscoring the need for further standardized research.<br><br>CONCLUSIONS: Fasting and caloric restriction have shown potential benefits in managing LCS symptoms like fatigue, cognitive decline, and inflammatory symptoms. Nonetheless, the diversity of study designs and outcomes necessitates more rigorous research to confirm the effectiveness and safety of interventions for LCS management. Future studies should focus on long-term effects and biological mechanisms and include broader, more diverse populations to enhance generalizability and support clinical guidance.},
}
@article {pmid40964918,
year = {2025},
author = {Woldegiorgis, M and Bloomfield, L and Korda, R and Cadby, G and Ngeh, S and Knight, P and Jardine, A and Maticevic, J and Armstrong, P and Effler, P},
title = {Factors associated with persistence or recovery from long COVID 6 months post-SARS-CoV-2 infection.},
journal = {Epidemiology and infection},
volume = {153},
number = {},
pages = {e116},
pmid = {40964918},
issn = {1469-4409},
mesh = {Humans ; *COVID-19/epidemiology/physiopathology/complications ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; Time Factors ; Risk Factors ; Fatigue ; },
abstract = {There are limited data on the illness trajectory for individuals with long COVID. We prospectively followed 1,234 individuals with long COVID at 3 months post-SARS-CoV-2 infection to identify factors associated with persistence or recovery. At 6 months post-infection, 724 (58.7%) had persistent long COVID and 510 (41.3%) had fully recovered. In multivariable analyses, pre-existing health conditions at the time of initial SARS-CoV-2 infection and reporting fatigue, shortness of breath, and cough 3 months post-infection were independent predictors of persistent long COVID. Age, sex, and number of COVID vaccinations were not significantly associated with persistent long COVID. For persons with persistent long COVID, the median number of symptoms remained stable over follow-up, indicating that there had been little symptomatic improvement. A third of those with persistent long COVID reported seeking medical care for their symptoms and a third had ceased or reduced their hours of work/study. Our findings suggest that there may be distinct clinical trajectories for long COVID observed between 3- and 6-month follow-up, that is, persons who experience full recovery and those with minimal clinical improvement, and this may have implications for management of affected individuals.},
}
@article {pmid40964469,
year = {2025},
author = {Pearson, L and Maina, A and Compratt, T and Harden, S and Aaroe, A and Copas, W and Thompson, L},
title = {Correction: Stellate Ganglion Block Relieves Long COVID-19 Symptoms in 86% of Patients: A Retrospective Cohort Study.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {c295},
doi = {10.7759/cureus.c295},
pmid = {40964469},
issn = {2168-8184},
abstract = {[This corrects the article DOI: 10.7759/cureus.45161.].},
}
@article {pmid40959166,
year = {2025},
author = {Tankéré, P and Lajeune, E and Mariet, AS and Cottenet, J and Beltramo, G and Georges, M and Bonniaud, P and Favrolt, N and Quantin, C},
title = {Long-term in-hospital mortality and chronic thromboembolic pulmonary hypertension after COVID-19-associated pulmonary embolism in France: a nationwide study.},
journal = {ERJ open research},
volume = {11},
number = {5},
pages = {},
pmid = {40959166},
issn = {2312-0541},
abstract = {BACKGROUND: Although long-term effects of coronavirus disease-2019 (COVID-19) such as dyspnoea are frequent, the mechanisms are often poorly understood. The endothelial effects of COVID-19, such as venous or arterial thrombosis, are also well documented. Thus, the incidence of chronic thromboembolic pulmonary hypertension (CTEPH) following COVID-19 is an issue with many implications, particularly for screening in patients with long COVID.<br><br>METHODS: From the French National Hospital Discharge database (March 2020 to December 2021), we included all adults hospitalised for pulmonary embolism (PE). To study the hospital incidence of CTEPH, we excluded patients with previous pulmonary hypertension diagnoses. Then, in the 2&#x2005;years following the admission for PE, we compared the hospital incidence of CTEPH between PE patients with COVID-19 (COVID-PE) and without (non-COVID-PE). We also studied in-hospital mortality.<br><br>RESULTS: Among the 136&#x2009;505 patients included, 1.68% were diagnosed with CTEPH in the following 2&#x2005;years with a significant difference between COVID-PE and non-COVID-PE (0.77% versus 1.82%; p<0.0001). The 2-year in-hospital mortality was significantly lower in COVID-PE than in non-COVID-PE (4.82% versus 13.34%; p<0.0001). These results were confirmed by multivariate analyses. Among COVID-PE, we found no difference in the hospital incidence of CTEPH between 2020 and 2021, while after the initial discharge, in-hospital mortality was significantly higher in 2020 compared with 2021.<br><br>CONCLUSION: When investigating chronic dyspnoea in patients hospitalised for COVID-19 associated with PE, the risk of CTEPH should not be considered higher than for other PE. COVID-19 associated with hospitalised PE should not be considered an additional harmful factor if not associated with initial in-hospital mortality.},
}
@article {pmid40958852,
year = {2025},
author = {Zhu, Y and Quan, P and Yamazaki, T and Norweg, A and Natelson, B and Xu, X},
title = {Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.},
journal = {Immunometabolism (Cobham, Surrey)},
volume = {7},
number = {4},
pages = {e00068},
pmid = {40958852},
issn = {2633-0407},
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID are complex, disabling conditions that have emerged as significant public health challenges, affecting millions worldwide. Despite their growing prevalence, effective diagnostics and treatments remain limited, largely due to an incomplete understanding of their underlying pathophysiology. Both conditions share hallmark symptoms of chronic fatigue, cognitive dysfunction, and postexertional malaise, but their biological underpinnings remain to be elucidated. Neuroimaging offers a promising, noninvasive window into the brain's metabolic landscape and has the potential to uncover objective biomarkers for these conditions. In this mini review, we highlight recent advancements in metabolic neuroimaging, particularly positron emission tomography and magnetic resonance imaging/magnetic resonance spectroscopy, that reveal alterations in glucose and oxygen metabolism, neurotransmitter balance, and oxidative stress. These insights point toward shared disruptions in brain energy metabolism and neuroinflammatory processes, which may underlie the persistent symptoms in both ME/CFS and Long-COVID. Importantly, while some findings overlap, inconsistencies in metabolite profiles between ME/CFS and Long-COVID underscore the need for further stratification and longitudinal research. Standardizing definitions, such as identifying Long-COVID patients who meet ME/CFS diagnostic criteria, could help improve study comparability. By summarizing current imaging evidence, this review underscores the potential of neuroimaging to identify imaging biomarkers to advance the clinical diagnosis of Long-COVID and identify therapeutic targets for treatment development. As we continue to face the growing burden of Long-COVID and ME/CFS, metabolic imaging may serve as a powerful tool to bridge gaps in knowledge and accelerate progress toward effective care.},
}
@article {pmid40957873,
year = {2025},
author = {Maybin, JA and Walker, C and Watters, M and Homer, NZ and Simpson, JP and Robb, C and Gibson, DA and Jeanjean, L and Critchley, HOD and Kountourides, G and Olszewska, Z and Alvergne, A},
title = {The potential bidirectional relationship between long COVID and menstruation.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8187},
pmid = {40957873},
issn = {2041-1723},
support = {209589/Z/17/Z//Wellcome Trust (Wellcome)/ ; R47180//Royal Society of Edinburgh (RSE)/ ; RTF1103//Wellbeing of Women/ ; /WT_/Wellcome Trust/United Kingdom ; G1002033, MR/N022556/1//RCUK | Medical Research Council (MRC)/ ; },
mesh = {Humans ; Female ; *COVID-19/complications/physiopathology/blood ; Adult ; Endometrium/metabolism ; SARS-CoV-2 ; *Menstruation/physiology ; Menstrual Cycle/physiology ; United Kingdom/epidemiology ; *Menstruation Disturbances ; Middle Aged ; Cytokines/blood ; Young Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {Women have reported menstrual changes following SARS-CoV-2 infection and variation in long COVID symptoms across the menstrual cycle. We examined (i) whether COVID is linked to abnormal uterine bleeding (AUB), (ii) if long COVID symptoms vary with the menstrual cycle, and (iii) potential underlying mechanisms. Here we show long COVID was associated with AUB in a UK population. When compared to those never infected (n = 9423), long COVID participants (n = 1048) reported increased menstrual volume, duration and intermenstrual bleeding, while those who recovered from acute COVID (n = 1,716) reported minimal menstrual disruption. Long COVID symptoms examined in 54 women across the menstrual cycle revealed that severity was highest during the perimenstrual and proliferative phases. Serum and endometrial analysis revealed higher serum 5α-dihydrotestosterone and lower endometrial androgen receptors in long COVID versus no COVID. Other ovarian hormones showed no significant differences. Serum cytokine profiling indicated increased menstrual inflammation with long COVID and immune cell aggregates were observed in menstrual endometrium. In conclusion, long COVID was associated with AUB but not impaired ovarian function. Differences in peripheral and endometrial inflammation may contribute to AUB and long COVID symptom severity. We anticipate our findings will instigate exploration of new therapeutic strategies for women with long COVID.},
}
@article {pmid40956375,
year = {2025},
author = {Naushad, Z and Malik, J and Mishra, AK and Singh, S and Shrivastav, D and Sharma, CK and Verma, VV and Pal, RK and Roy, B and Sharma, VK},
title = {Artificial Intelligence in Cardiovascular Health: Insights into Post-COVID Public Health Challenges.},
journal = {High blood pressure &amp; cardiovascular prevention : the official journal of the Italian Society of Hypertension},
volume = {32},
number = {5},
pages = {475-494},
pmid = {40956375},
issn = {1179-1985},
mesh = {Humans ; *COVID-19/epidemiology ; *Cardiovascular Diseases/diagnosis/epidemiology/therapy ; *Artificial Intelligence ; *Public Health ; Risk Assessment ; SARS-CoV-2/pathogenicity ; Risk Factors ; },
abstract = {Cardiovascular diseases (CVDs) continue to be the topmost cause of the worldwide morbidity and mortality. Risk factors such as diabetes, hypertension, obesity and smoking are significantly worsening the situation. The COVID-19 pandemic has powerfully highlighted the undeniable connection between viral infections and cardiovascular health. Current literature highlights that SARS-CoV-2 contributes to myocardial injury, endothelial dysfunction, thrombosis, and systemic inflammation, increasing the severity of CVD outcomes. Long COVID has also been associated with persistent cardiovascular complications, including myocarditis, arrhythmias, thromboembolic events, and accelerated atherosclerosis. Addressing these challenges requires continued research and public health strategies to mitigate long-term risks. Artificial intelligence (AI) is changing cardiovascular medicine and community health through progressive machine learning (ML) and deep learning (DL) applications. AI enhances risk prediction, facilitates biomarker discovery, and improves imaging techniques such as echocardiography, CT, and MRI for detecting coronary artery disease and myocardial injury on time. Remote monitoring and wearable devices powered by AI enable real-time cardiovascular assessment and personalized treatment. In public health, AI optimizes disease surveillance, epidemiological modeling, and healthcare resource allocation. AI-driven clinical decision support systems improve diagnostic accuracy and health equity by enabling targeted interventions. The integration of AI into cardiovascular medicine and public health offers data-driven, efficient, and patient-centered solutions to mitigate post-COVID cardiovascular complications.},
}
@article {pmid40956349,
year = {2025},
author = {Corrêa-Dias, LC and Lopes-Ribeiro, &#xc1; and Mendes, GER and Marques-Ferreira, G and Wilker-Teixeira, C and Clarindo, FA and de Melo Rocha, V and Martuchele-Félix, ME and Retes, HM and Santos, TAP and Azevedo, GLA and Pereira, VEV and de Fátima Silva Moraes, T and de Sousa Reis, EV and Gomes-de-Pontes, L and Rabelo, LF and Dos Santos, EAS and Pereira, CLD and Coelho, FDS and Coelho, RP and Santos, RA and Coelho, GP and da Fonseca, FG and Coelho-Dos-Reis, JGA},
title = {A pain from the nose to the head: neurological commitment during long COVID.},
journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]},
volume = {74},
number = {1},
pages = {127},
pmid = {40956349},
issn = {1420-908X},
mesh = {Humans ; *COVID-19/complications/immunology ; *Neuroinflammatory Diseases/immunology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID is a debilitating illness with multi-systemic symptoms that affects at least 10% of individuals who have had COVID-19. Symptoms include respiratory, dermatological, gastrointestinal, cardiovascular, and most frequently reported, neurological sequelae. The most common neurological manifestations include fatigue, brain fog, memory issues, attention disorder, and headaches.<br><br>METHODS: In this review, we explore the current literature and highlight key findings regarding not only the clinical presentations of neurological commitment during long COVID but mainly the mechanisms that culminate in neuroinflammation, such as autoimmunity, viral reservoirs, and lack of surveillance of T-cells.<br><br>RESULTS: Neuroinflammation is a complex multicellular response that directly impacts microglial cells and includes inflammasome activation, trafficking of immune cells, and increased circulating autoantibodies, cytokines, and chemokines in the central nervous system, directly impacting the tissue homeostasis. This review provides important information beyond the clinical manifestations of long COVID. Here, we highlight multifactorial neuroinflammation as the main mechanism involved in long COVID, bringing together several studies that address the different mechanisms that culminate in inflammation of the central nervous system, and highlight possible biomarkers involved in this syndrome and potential therapeutic approaches that have been studied.<br><br>CONCLUSION: Thus, this review strengthens research into long COVID and provides new possibilities for future studies.},
}
@article {pmid40954621,
year = {2025},
author = {Cunha, BLM and Policarpo, JH and Silva, JRD and Porfírio, PV and Fraga, LRDS and Leitão, CCS and Marinho, PEM},
title = {Whole body vibration exercise effects on exercise capacity and muscle strength in long Covid-19 patients: A randomized clinical trial.},
journal = {Journal of bodywork and movement therapies},
volume = {44},
number = {},
pages = {494-500},
doi = {10.1016/j.jbmt.2025.06.013},
pmid = {40954621},
issn = {1532-9283},
}
@article {pmid40954187,
year = {2025},
author = {van der Bie, J and Coleon, A and Visser, D and Bogers, WM and den Dunnen, J and Spronk, HMH and Langermans, JAM and Willemen, HLDM and De Melo, GD and Middeldorp, J and Stammes, MA},
title = {Post Pandemic Problem, is there an animal model suitable to investigate PASC.},
journal = {Npj imaging},
volume = {3},
number = {1},
pages = {41},
pmid = {40954187},
issn = {2948-197X},
support = {11080012310002/ZONMW_/ZonMw/Netherlands ; },
abstract = {Although the COVID-19 pandemic is no longer a global health emergency, many patients still suffer from long-term effects, known as post-acute sequelae of COVID-19 (PASC) or long COVID. Understanding its complex pathophysiology requires animal models replicating the post-acute phase, which may aid in developing, the urgently needed, therapeutics. Our review assessed and summarized 81 studies from 1979 manuscripts. In addition, a second table summarizing the imaging findings of 26 studies related to this topic was added, based on a separate literature search of 797 manuscripts. In humans a SARS-CoV-2 infection, the sequelae and possible development of PASC is heterogenic. The same holds true for experimental animal models. While several models are suitable to address different research questions, no single model can fully replicate all aspects of PASC. Imaging plays a crucial role in visualizing these aspects, especially since questionnaires, the primary diagnostic tool in humans, cannot be used in animals. Thus, imaging allows the investigation of pathophysiology in a controlled setting, offering valuable insights. This review summarizes the available animal models and imaging modalities used in PASC research. Our aim is to provide researchers with guidance on selecting the most appropriate model and imaging technique to address their specific research questions.},
}
@article {pmid40953722,
year = {2025},
author = {Holtjer, JCS and Houweling, L and Bloemsma, LD and Cornelissen, MEB and Maitland-Van der Zee, AH and Portengen, L and Kakhaia, S and Vermeulen, RCH and Downward, GS and , },
title = {Defining a long COVID 'expotype' within the P4O2 COVID-19 study.},
journal = {Environmental research},
volume = {286},
number = {Pt 2},
pages = {122860},
doi = {10.1016/j.envres.2025.122860},
pmid = {40953722},
issn = {1096-0953},
mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; *Fatigue/epidemiology/etiology ; Netherlands/epidemiology ; Quality of Life ; Adult ; Aged ; SARS-CoV-2 ; Air Pollutants/analysis ; *Environmental Exposure ; Severity of Illness Index ; },
abstract = {INTRODUCTION: Long COVID is estimated to affect at least 10 % of COVID-19 patients, with fatigue being a common complaint. The combined contribution of environmental factors (i.e. exposome) has been associated with COVID-19 severity, however its association with long COVID remains underexplored. This study aims to identify possible exposome phenotypes ('expotypes') related to long COVID severity.<br><br>METHODS: We recruited 95 long COVID patients in the Netherlands and assessed a range of factors and symptoms at 3-6 months post-infection. Fatigue (FSS), Quality of Life (QoL) and fatigue over time were used as indicators of long COVID severity. We included air pollutants (n&#xa0;=&#xa0;4), and neighborhood characteristics (n&#xa0;=&#xa0;7). We performed frequentist and Bayesian analyses to determine factors associated with long COVID severity. Models were adjusted for age, BMI, education level, and sex.<br><br>RESULTS: We found population density (odds ratio (OR)[95&#xa0;%Confidence interval(CI)]&#xa0;=&#xa0;1.03[1.01-1.06]) and light at night (OR[95&#xa0;%CI]&#xa0;=&#xa0;0.95[0.90-1.00]) to be associated with fatigue. Decreased odds for having an optimal QoL score was found for increased distance to blue space (OR[95&#xa0;%CI]&#xa0;=&#xa0;0.41[0.15-0.93]) in the single exposure model. No significant associations were found for any exposure variables and fatigue over time. No exposure variables were selected in penalized regression models for any outcome.<br><br>DISCUSSION: The external exposome could be associated with fatigue severity and QoL in long COVID patients, however these associations were not found in the horseshoe model. Prevention strategies and urban planning could take these associations into account to optimize the living environment, however more research is needed to validate and investigate the impact of these results.},
}
@article {pmid40953059,
year = {2025},
author = {Preiss, A and Bhatia, A and Aragon, LV and Baratta, JM and Baskaran, M and Blancero, F and Brannock, MD and Chew, RF and Díaz, I and Fitzgerald, M and Kelly, EP and Zhou, AG and Carton, TW and Chute, CG and Haendel, M and Moffitt, R and Pfaff, E and , },
title = {Effect of Paxlovid treatment during acute COVID-19 on Long COVID onset: An EHR-based target trial emulation from the N3C and RECOVER consortia.},
journal = {PLoS medicine},
volume = {22},
number = {9},
pages = {e1004711},
pmid = {40953059},
issn = {1549-1676},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; Electronic Health Records ; *COVID-19/complications/epidemiology ; Aged ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; Incidence ; },
abstract = {BACKGROUND: Preventing and treating post-acute sequelae of COVID-19 infection (PASC), commonly known as Long COVID, has become a public health priority. This study tests whether Paxlovid treatment in the acute phase of COVID-19 could help prevent the onset of PASC.<br><br>METHODS AND FINDINGS: We used electronic health records from the National Clinical Cohort Collaborative to define a cohort of 445,738 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation framework to estimate the effect of Paxlovid treatment on PASC incidence. We emulated a series of six sequential trials: one for each day of a 5-day treatment grace period. For each sequential trial, the treatment group was defined as patients prescribed Paxlovid on the trial start day, and the control group was defined as all patients meeting eligibility criteria who remained untreated on the trial start day. We pooled individual record-level data from the sequential trials for analysis. The follow-up period was 180 days. The primary outcome was overall PASC incidence measured using a computable phenotype. Secondary outcomes were incident cognitive, fatigue, and respiratory symptoms in the post-acute period. We controlled for a wide range of demographic and medical history covariates. Compared to the control group, Paxlovid treatment did not have a significant effect on overall PASC incidence or incident respiratory symptoms. It had a small protective effect against cognitive (relative risk [RR] 0.91; 95% CI [0.84, 0.98]; p&#x2009;=&#x2009;0.019) and fatigue (RR 0.94; 95% CI [0.90, 0.98]; p&#x2009;=&#x2009;0.002) symptoms. Finally, we estimated Paxlovid's effect on overall PASC incidence across strata of age, COVID-19 vaccination status, and Charlson Comorbidity Index (CCI) prior to COVID-19. We found small protective effects among patients aged 65 years or more (RR 0.92; 95% CI [0.88, 0.97]; p&#x2009;<&#x2009;0.001; absolute risk difference [ARD] -0.43%; number needed to treat [NNT] 233) and with a CCI of 3 or 4 (RR 0.83; 95% CI [0.75, 0.92]; p&#x2009;<&#x2009;0.001; ARD -1.30%; NNT 76). This study's main limitation is that the causal interpretation relies on the assumption that we controlled for all confounding variables.<br><br>CONCLUSIONS: Although some prior observational studies suggested that Paxlovid held promise as a PASC preventive, this study-with a large, nationally sampled cohort; a contemporary study period; and causal inference methodology-found that Paxlovid treatment during acute COVID-19 had no effect on subsequent PASC incidence. Stratified analyses suggest that Paxlovid may have a small protective effect among higher-risk patients, but the NNT is high. In conclusion, we see Paxlovid as unlikely to become a definitive solution for PASC prevention.},
}
@article {pmid40951275,
year = {2025},
author = {Parthasarathy, S and Brosnahan, S and Sieberts, S and Neto, E and Li, Y and Tummalacherla, M and Brown, HE and Chow, SM and Dunn, J and Haack, M and Islam, SM and Jacobs-Diggs, M and Jiang, Y and Kossowsky, J and Prather, A and Raytselis, N and Salimi, N and Ayache, M and Bartram, L and Becker, J and Chung, A and DelAlcazar, J and Flaherman, V and Gibson, K and Go, M and Gouripeddi, R and Han, J and Hoffman, M and Jolley, S and Kelly, J and Koberssy, Z and Krishnan, J and Laiyemo, A and Lee-Iannotti, J and Levitan, E and Mazzotti, D and McComsey, G and Mehari, A and Okomura, M and Patterson, T and Peluso, M and Prasad, B and Quintero, O and Ryerson, A and Singh, P and Singh, U and Verduzco-Gutierrez, M and Whitesell, P and Williams, N and Wisnivesky, J and Mullington, J and Redline, S and Karlson, E},
title = {Wearable-derived Sleep Measurements are Associated with Long-COVID in the RECOVER Adult Cohort.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40951275},
issn = {2693-5015},
support = {OT2 HL158287/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; R25 HL126140/HL/NHLBI NIH HHS/United States ; },
abstract = {Wearables yield a wide array of sleep-related measures that are relevant to Long COVID. We leveraged wearables-derived sleep measures (WDSM) to identify differences between individuals with Long COVID (LC) versus individuals with possible or no LC in the RECOVER adult cohort. We found significant associations between LC and reduced heart rate variability measured during sleep and increased nightly variability in sleep duration after adjusting for confounders. Moreover, LC was independently associated with lower sleep efficiency, greater variability of nighttime sleep timing, higher resting heart rate, lower respiratory rate during rapid eye movement (REM) sleep, prolonged REM sleep onset latency, worse global physical and mental health. Cluster analysis identified distinct multidimensional patterns of WDSM that are associated with LC and quality of life. Together, the strong association between WDSM, or WDSM clusters, with LC provides a potential biomarker for future validation efforts to detect LC and monitor treatment effectiveness.},
}
@article {pmid40950970,
year = {2025},
author = {Matviichuk, A and Krasnienkov, D and Yerokhovych, V and Ilkiv, Y and Korcheva, V and Gurbych, O and Shcherbakova, A and Botsun, P and Falalyeyeva, T and Sulaieva, O and Kobyliak, N},
title = {Association of leukocyte telomere length and HbA1c with post-COVID-19 syndrome in type 2 diabetes: a cross-sectional pilot study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1628156},
pmid = {40950970},
issn = {2296-858X},
abstract = {INTRODUCTION: Leukocyte telomere length is considered a promising prognostic marker associated with COVID-19 severity, adverse outcomes (hospital admission, need for critical care, and respiratory support), and mortality. However, the contribution of telomere length to post-COVID-19 syndrome (PCS) development is unclear.<br><br>AIM: This study aimed to evaluate the association between telomere shortening and the course of PCS in patients with type 2 diabetes (T2D) and to determine whether telomere length is linked to clinical phenotype, gender, and biological age.<br><br>MATERIALS AND METHODS: In this cross-sectional study, 66 T2D patients who had recovered from COVID-19 were enrolled. Patients were divided into two groups depending on PCS development: the PCS group (n =&#x202f;44) and patients who did not develop PCS (n =&#x202f;22) within 6&#x202f;months after COVID-19 infection. Relative telomere length was determined using the standardized method proposed by Cawthon et al. A range of machine learning models was developed for PCS prediction. These models underwent training utilizing a cross-validation approach, as well as internal validation.<br><br>RESULTS: We observed a significantly lower mean of telomere length in T2D patients with PCS as compared to those without it (1.09&#x202f;&#xb1;&#x202f;0.19 and 1.28&#x202f;&#xb1;&#x202f;0.24; p&#x202f;=&#x202f;0.001). In the sub-analysis, shorter telomeres were observed in female patients and patients of older age in both groups. The mean telomere length did not differ significantly among clinical phenotypes of PCS (p&#x202f;=&#x202f;0.193). The best model generated for PCS prediction was the gradient boosting machine (GBM), which achieved an AUC of 0.753. The most influential variables across the top 10 models included telomere length, HbA1c, vitamin D3, waist circumference, ApoA1, C peptide, ApoB, COVID-19 severity, duration of T2D, IL-6, cholesterol, BMI, and age. Leukocyte telomere length and HbA1c exhibited significantly greater impact than other features.<br><br>CONCLUSION: Shorter telomere length and higher HbA1c levels were significantly associated with the presence of PCS in our cohort of individuals with T2D. These factors may represent potential biomarkers that warrant further investigation.},
}
@article {pmid40950924,
year = {2025},
author = {Meiler, S and Schmalenberger, D and Malfertheiner, M and Dvorak, I and Strotzer, Q and Stroszczynski, C and Hamer, OW},
title = {Chest computed tomography findings do not influence the decision of pneumologists regarding the diagnosis and management of pulmonary long coronavirus disease: a single center retrospective study.},
journal = {Journal of thoracic disease},
volume = {17},
number = {8},
pages = {5654-5662},
pmid = {40950924},
issn = {2072-1439},
abstract = {BACKGROUND: Pulmonary symptoms are common in long coronavirus disease (COVID), yet the diagnostic value of chest computed tomography (CT) in these patients remains unclear, particularly when physical examination and pulmonary function tests are normal. This study investigates whether chest CT influences the decision of pneumologists regarding the measures taken for diagnostic work-up, the final diagnosis, the confidence in the diagnosis, and the downstream management of patients suspected to suffer from pulmonary long COVID.<br><br>METHODS: All patients presented in a dedicated long COVID outpatient clinic of a secondary care hospital that specializes in lung diseases between April 2020 and August 2021. Inclusion criteria were age &#x2265;18 years, suspicion for long COVID syndrome of pulmonary origin according to the National Institute for Health and Care Excellence (NICE) criteria and availability of a chest CT acquired during work-up. Three pneumologists evaluated the patient's records in two rounds (round 1 without and round 2 with knowledge of CT results). Identical parameters were queried in the two runs: diagnosis of pulmonary long COVID, confidence of the diagnosis on a scale from 0 to 3, need for: bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), cryobiopsy, video-assisted thoracoscopy (VATS), ergospirometry, ventilation/perfusion scintigraphy, follow-up appointment, rehabilitation.<br><br>RESULTS: Forty-one patients were included (24 male; age 21 to 72 years, mean 55 years). In the first and second round diagnosis of pulmonary long COVID was made in an average of 10 (24%) and 11 (27%) patients (P=0.69). Confidence of diagnosis was 1.9 and 2.6 (P<0.001). No statistical difference was found regarding the frequency of diagnostic measures and downstream management.<br><br>CONCLUSIONS: Chest CT did not influence the diagnostic decision of pneumologists for patients suspected to suffer from pulmonary long COVID. However, the confidence in the diagnosis was improved by chest CT. Still, based on our results chest CT does not routinely have to be included in the work-up of long COVID, when pulmonary function tests and auscultation are normal.},
}
@article {pmid40950852,
year = {2025},
author = {Li, X and Chen, Y and Sun, S and Dong, H and Luo, J},
title = {Association between electrolyte supplementation and cardiac injury in long COVID-19.},
journal = {Journal of thoracic disease},
volume = {17},
number = {8},
pages = {5993-6003},
pmid = {40950852},
issn = {2072-1439},
abstract = {BACKGROUND: Cardiac injury is a common complication of long coronavirus disease 2019 (COVID-19), affecting heart function and quality of life. This study aimed to investigate the association between electrolyte supplementation and cardiac injury in long COVID-19.<br><br>METHODS: This retrospective study was conducted at Guangdong Provincial People's Hospital Zhuhai Hospital (Zhuhai Golden Bay Hospital), utilizing data from patients with cardiac injury related to long COVID-19 who were admitted and managed between January 2021 and January 2023. The patients were grouped according to electrolyte supplementation (supplementation group) or no supplementation (control group). The outcomes included heart rate variability (HRV) parameters, the Minnesota Heart Failure Quality of Life questionnaire, and numerical rating scale (NRS) assessments of quality of life.<br><br>RESULTS: A total of 144 patients with cardiac injury related to long COVID-19 were included in the analysis (supplementation group, n=72; control group, n=72). After adjusting for age, sex, creatinine, total cholesterol, and low-density lipoprotein, multivariable linear regression analysis indicated a significant association between supplementation and increased levels of potassium [&#x3b2;=1.3, 95% confidence interval (CI): 1.1-1.5, P=0.001] and magnesium (&#x3b2;=0.18, 95% CI: 0.07-0.29, P=0.001), as well as improvements in HRV parameters, including standard deviation of normal-to-normal RR intervals over 24 hours, root mean square of successive differences, and high-frequency domain indices/low-frequency domain indices (all P<0.05). Additionally, supplementation correlated with a reduced frequency of premature contractions (&#x3b2;=-5.61, 95% CI: -7.50 to -3.72, P=0.01), lower Minnesota scores (&#x3b2;=-6.7, 95% CI: -9.1 to -4.3, P=0.001), and decreased NRS scores (&#x3b2;=-7.2, 95% CI: -6.5 to -7.9, P=0.02).<br><br>CONCLUSIONS: Electrolyte supplementation may be beneficial in managing cardiac injury associated with long COVID-19. Further research is needed to clarify the role of electrolytes in cardiac injury related to long COVID-19 and to explore management strategies that incorporate electrolyte supplementation.},
}
@article {pmid40950756,
year = {2025},
author = {Tusconi, M and Dursun, SM and Pegreffi, F and Aviles Gonzalez, CI and Barrui, V and Fornaro, M and Hurtado Lujan, LA and Camacho Nunez, LP and Vega Ochoa, AD and Curcio, F and Carta, MG and Cossu, G},
title = {Bipolar spectrum, hypothyroidism, and their association with chronic fatigue/myalgic encephalomyelitis-like syndrome in long COVID: could they be identified as early determinants?.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1623288},
pmid = {40950756},
issn = {1664-0640},
abstract = {BACKGROUND: Long COVID has been increasingly linked to persistent clinical manifestations, including chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). However, the relationship between this syndrome and pre-existing conditions such as bipolar spectrum disorders and hypothyroidism is not yet clearly established. These disorders may influence the regulation of biorhythms and immune function, suggesting a possible role in the predisposition to the development of CFS/ME in the context of long-term COVID-19.<br><br>OBJECTIVES: This study investigates the prevalence of hypothyroidism and bipolar spectrum disorders in patients with CFS/ME associated with long-term COVID-19. It compares it with pre-pandemic population data to determine whether these conditions may be predisposing factors.<br><br>METHODS: A case-control design was used to select cases from a clinical trial on CFS/ME in long COVID, while controls were extracted from pre-COVID epidemiological databases. Comparative statistical analyses, including chi-square tests and analysis of variance (ANOVA), were performed to assess significant differences in the frequency of these conditions between both groups.<br><br>RESULTS: The clinical sample showed significantly higher prevalence rates of hypothyroidism [27.78% vs. 1.14%; odds ratio (OR) = 33.07; 95% confidence interval (CI): 7.10-153.70] and bipolar spectrum disorders (16.67% vs. 0.2%; OR = 138.4; 95% CI: 36.40-526.43) compared to control populations (p < 0.0001 for both). Similarly, individuals screening positive for depressive symptoms (PHQ9 > 9) showed markedly increased odds (55.5% vs. 4.16%; OR = 28.75; 95% CI: 6.52-126.73).<br><br>CONCLUSION: The findings suggest that hypothyroidism and bipolar spectrum disorders may act as predisposing factors in the development of CFS/ME in long-term COVID-19. Identifying these clinical antecedents could facilitate early detection and the development of targeted intervention strategies in at-risk populations.},
}
@article {pmid40949692,
year = {2025},
author = {Santo, K and Favaro, L and Martins, E},
title = {Following the Pandemic: Exploring Long COVID's impact on Global Health through the World Heart Federation Global COVID-19 Study.},
journal = {Global heart},
volume = {20},
number = {1},
pages = {79},
pmid = {40949692},
issn = {2211-8179},
mesh = {Humans ; *COVID-19/epidemiology/complications ; *Global Health ; SARS-CoV-2 ; *Pandemics ; Cost of Illness ; Post-Acute COVID-19 Syndrome ; },
abstract = {Although the COVID-19 pandemic crisis has come to an end, Long COVID continues to pose a profound challenge to global health. Based on findings from the World Heart Federation (WHF) Global COVID-19 Study, an international prospective cohort study, this editorial reflects on the enduring burden of symptoms and complications among 2,535 previously hospitalized patients across 16 countries during the Omicron era. Beyond a mortality rate of 15% and clinical manifestations such as fatigue, dyspnea, and adverse cardiovascular events, the study highlighted substantial psychosocial and socioeconomic impacts, with reduced work capacity and functional limitations particularly affecting populations in low- and middle-income countries captured through EuroQol 5-dimension scale and employment data. These findings emphasize that the burden of Long COVID extends beyond individual health, with significant implications for healthcare systems and economic stability. Addressing this challenge requires ongoing multidisciplinary research, validated diagnostic criteria, novel biomarkers, and effective preventive and therapeutic strategies. Furthermore, decentralized monitoring models-exemplified by telephone-based data collection in the WHF study-may offer scalable approaches to improve surveillance and inform global health policies for current and future public health crises.},
}
@article {pmid40948805,
year = {2025},
author = {Liu, C and Liu, C and Yan, R and Becker, D and Shi, JX and Slezak, J and Jerng, D},
title = {Association of COVID vaccinations and treatments with long COVID beyond 6 months: a case-control study on the adult population in a large integrated healthcare system in the United States from 2020 to 2023.},
journal = {Preventive medicine reports},
volume = {57},
number = {},
pages = {103188},
pmid = {40948805},
issn = {2211-3355},
abstract = {OBJECTIVE: Long coronavirus disease (Long COVID) is a chronic condition causing significant long-term disability and economic burden. This study aims to measure the association between COVID vaccinations and treatment at the time of acute infection with Long COVID outcomes beyond six months post-infection, controlling for demographic and medical variables.<br><br>METHODS: This retrospective case-control study used electronic medical records from Kaiser Permanente Southern California to evaluate Long COVID outcomes from January 2022 to June 2023 with vaccination doses and nirmatrelvir/ritonavir, and from October 2020 to June 2023 with remdesivir and other treatments. Statistical analysis used univariate chi-square and Kruskal-Wallis tests and conditional logistic regression.<br><br>RESULTS: Our study had 840 (January 2022 analysis) and 2632 (October 2020 analysis) Long COVID patients diagnosed by International Classification of Diseases-10 code at least 6&#xa0;months after acute COVID infection with 1:5 matched controls by age, sex, race/ethnicity, Body Mass Index, and date of acute COVID infection. Long COVID outcome was inversely associated with the number of COVID vaccination doses (one dose odds ratio (OR) 0.77; 95&#xa0;% CI 0.63-0.96, two doses OR 0.73; 95&#xa0;% CI 0.59-0.92, three doses OR 0.64; 95&#xa0;% CI 0.44-1.00, four doses OR 0.29; 95&#xa0;% CI 0.06-1.49) and nirmatrelvir/ritonavir (OR 0.05; 95&#xa0;% CI 0.04-0.07) or remdesivir (OR 0.31; 95&#xa0;% CI 0.19-0.49) treatment with no interaction between three vaccinations with nirmatrelvir/ritonavir and four vaccinations with remdesivir treatment.<br><br>CONCLUSION: These findings may influence existing clinical practices for vaccination and antiviral treatment strategies to decrease Long COVID consequences.},
}
@article {pmid40947853,
year = {2026},
author = {Brode, WM and Posada, J and Nagireddy, D},
title = {Ketamine as a Potential Neuromodulatory Treatment for Long COVID Neuropsychiatric and Neuropathic Symptoms: A Case Report.},
journal = {Journal of clinical psychopharmacology},
volume = {46},
number = {1},
pages = {103-105},
pmid = {40947853},
issn = {1533-712X},
}
@article {pmid40946369,
year = {2025},
author = {Liira, H and Varonen, M and Venäläinen, MS and Arokoski, J and Kvarnström, K and Vuokko, A and Malmivaara, A},
title = {Associations of socioeconomic status and health-related quality of life in patients with long COVID and patients with persistent physical symptoms: A comparison of two cohort studies at baseline.},
journal = {Journal of psychosomatic research},
volume = {197},
number = {},
pages = {112374},
doi = {10.1016/j.jpsychores.2025.112374},
pmid = {40946369},
issn = {1879-1360},
mesh = {Humans ; *Quality of Life/psychology ; Female ; Male ; Adult ; *COVID-19/psychology/epidemiology/complications ; Middle Aged ; *Social Class ; Cohort Studies ; Finland/epidemiology ; Surveys and Questionnaires ; },
abstract = {BACKGROUND AND AIM: Emerging evidence suggest a significant association between Long COVID (LC) and other persistent physical symptoms (PPS) with lower socioeconomic status (SES). We investigated the relationship between SES and health-related quality of life (HRQOL), as measured by the 15D and the EUROHIS-QOL-8 instruments, among patients with LC and those experiencing other PPS-related conditions.<br><br>METHODS: Factors related to clinical and socioeconomic aspects that affect HRQOL were evaluated using 15D, a validated 15-item self-reported questionnaire. Two parallel cohorts at Helsinki University Hospital were analyzed: the Helsinki LC cohort (n&#xa0;=&#xa0;422; 2021-2023) and the Helsinki Sympa cohort (n&#xa0;=&#xa0;599; 2020-2024), consisting of patients with PPS. Additionally, we performed an intersectional MAIHDA analysis of biopsychosocial predictors of quality of life.<br><br>RESULTS: The cohorts were demographically similar, with 70.6&#xa0;% and 66.4&#xa0;% female participants and mean ages of 44.8&#xa0;years (SD&#xa0;=&#xa0;11.3) and 38.8&#xa0;years (SD&#xa0;=&#xa0;11.0) in the LC and Sympa cohorts, respectively. By EUROHIS-QOL-8, 34&#xa0;% of LC and 41&#xa0;% of Sympa respondents rated their overall QOL as very bad or bad (scale options 1-2 out of 5). Mean 15D scores were 0.76 (SD&#xa0;=&#xa0;0.11) in the LC cohort and 0.74 (SD&#xa0;=&#xa0;0.11) in the Sympa cohort (scale: 0-1). Working status, comorbidities, and tertiary education emerged as key determinants in the information-criteria-based model, highlighting the cumulative burden of overlapping social and clinical disadvantages. No significant multiplicative effects were found within our cohorts.<br><br>CONCLUSIONS: Patients in both cohorts reported reduced HRQOL, and the influence of socioeconomic factors on QOL were highly similar. Comorbidities, only basic school education, and being out of work were associated with the lowest HRQOL scores. The accumulation of socioeconomic disadvantage may function as a barrier to treatment, and healthcare professionals should recognize these challenges and ensure that patients receive adequate support.},
}
@article {pmid40945655,
year = {2025},
author = {Yamada, G and Itaya, T and Iwamoto, N and Yamada, Y and Ogawa, Y and Suzuki, M and Morioka, S and Tochitani, K and Miyamori, D and Miyashita, J and Ohmagari, N and Yamamoto, Y},
title = {Development and validation of a simple 11-item long COVID burden index (LCBI).},
journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy},
volume = {31},
number = {11},
pages = {102809},
doi = {10.1016/j.jiac.2025.102809},
pmid = {40945655},
issn = {1437-7780},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; Middle Aged ; *Quality of Life ; *Patient Reported Outcome Measures ; Aged ; Surveys and Questionnaires ; Reproducibility of Results ; Adult ; SARS-CoV-2 ; *Cost of Illness ; Japan/epidemiology ; Factor Analysis, Statistical ; },
abstract = {BACKGROUND: Existing patient-reported outcome measures for long COVID are comprehensive; however, they are time-consuming and burdensome for some patients in daily practice.<br><br>OBJECTIVES: This study aimed to develop and validate a simple patient-reported outcome measure to assess the burden associated with frequently occurring symptoms in patients with long COVID.<br><br>METHODS: Following an extensive literature review, a questionnaire consisting of 11 items was developed based on the modified Delphi method with an expert panel. Its face validity was assessed in three individuals with COVID-19 history. The study subjects were Japanese residents who responded to the online QoLCoVE (Quality of Life in the COVID-19 Era) study between March 8 and April 1, 2024. The known-groups and concurrent validity were assessed after exploratory factor analysis. The internal consistency was evaluated using Cronbach's alpha.<br><br>RESULTS: A total of 1014 participants were included in the analysis, all at least two months after their last COVID-19 infection. The factor analysis results showed unidimensionality. Internal consistency reliability assessed using Cronbach's alpha was 0.89. For known-groups validity, the total score decreased with time since the acute COVID-19 infection, as well as with more frequent vaccinations, and increased with an increasing previous history of COVID-19. A dose-dependent relationship was observed between EQ-5D-5L and the scale's total score, categorized according to quartiles.<br><br>CONCLUSION: We successfully developed the Long COVID Burden Index, a simple 11-item scale to easily quantify symptoms frequently experienced by patients with long COVID, which may interfere with their daily lives.},
}
@article {pmid40944962,
year = {2025},
author = {Yong, SJ and Kenny, TA and Halim, A and Munipalli, B and Alhashem, YN and AlSaihati, H and Al-Subaie, MF and Al Kaabi, NA and Al Fares, MA and Garout, M and Sabour, AA and Alshiekheid, MA and Almansour, ZH and Alotaibi, J and Alrasheed, HA and Alamri, AA and Albayat, H and Alamodi, AS and Tombuloglu, H and Mohapatra, RK and Hazazi, A and Rabaan, AA},
title = {Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.},
journal = {Reviews in medical virology},
volume = {35},
number = {5},
pages = {e70070},
doi = {10.1002/rmv.70070},
pmid = {40944962},
issn = {1099-1654},
mesh = {Humans ; *COVID-19 Vaccines/adverse effects ; *COVID-19/prevention &amp; control/immunology ; *Vaccination/adverse effects ; SARS-CoV-2/immunology ; Fatigue Syndrome, Chronic ; Syndrome ; },
abstract = {With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.},
}
@article {pmid40944707,
year = {2026},
author = {Christensen, JFMM and Meyer, R and Holmqvist, M and Carlson, K and Palmqvist, S and Kahn, F and , and Jürgens, G and , },
title = {Cognitive sequelae in post-COVID-syndrome: a Danish-Swedish case-control study.},
journal = {Infectious diseases (London, England)},
volume = {58},
number = {1},
pages = {85-98},
doi = {10.1080/23744235.2025.2551665},
pmid = {40944707},
issn = {2374-4243},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Middle Aged ; Case-Control Studies ; Female ; Adult ; Denmark/epidemiology ; Aged ; SARS-CoV-2 ; Hand Strength ; Young Adult ; Sweden/epidemiology ; Adolescent ; *Cognitive Dysfunction/etiology ; Cognition ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: While patients with post-COVID syndrome (PCS) suffer from cognitive deficits few studies directly compare patients with PCS to subjects recovered after an infection with the 'Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)'.<br><br>OBJECTIVES: To investigate cognitive performance adjusting for age, increasing body-mass-index (BMI), smoking, years of education, gender and hospitalisation while infected in patients with PCS compared to controls fully recovered. Secondly, to stratify cognitive performance based on the SARS-CoV-2 virus strain (variant of concern 'VOC') causing the infection. Thirdly, to assess whether patients with PCS have increased levels of psychological distress and affected hand grip strength as both are associated with cognitive performance.<br><br>METHODS: A Danish-Swedish case-control study we recruited adult patients (18-75&#x2009;years) with PCS from long-COVID outpatient clinics in Region Zealand Denmark and Sk&#xe5;ne County Sweden. Participants had confirmed SARS-CoV-2 infection >12&#x2009;weeks prior to inclusion and healthy control subjects had recovered completely. All study participants were exposed to cognitive tests, Kessler's psychological distress scale (K10) and tested with a hand-dynamometer.<br><br>RESULTS: Recruiting 181 cases and 155 control subjects, patients with PCS had reduced cognitive performance scores on all domains though hardly clinically significant. Reduced processing speed was impacted the most with patients infected early in the pandemic exhibiting greater deficits.<br><br>CONCLUSION: PCS was associated with reduced cognitive processing speed compared to fully recovered controls with those infected early in the pandemic having greater deficits. Psychological distress and hand grip strength were affected in patients with PCS, but not decisively associated with cognitive performance.},
}
@article {pmid40943873,
year = {2025},
author = {Hansel Robinson, J and Bakir, H and James, AS and Brooks, MS and Thomas, SJ and Lokken, KL},
title = {Prevalence, Severity, Concomitant Factors, and Natural Trajectory of Insomnia in Patients with Long COVID.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943873},
issn = {2077-0383},
abstract = {Background/Objective: Insomnia is a clinically important symptom in Long COVID; however, few studies have addressed the presentation and course of insomnia symptoms in patients with Long COVID. Methods: The Insomnia Severity Index (ISI) was administered as part of a comprehensive baseline neuropsychological evaluation (Time 1) for patients with Long COVID at an Academic Medical Center (AMC). Data were gathered on 172 consecutively referred patients between the dates of November 2020 and May 2022. The mean age of patients at Time 1 was 49 years (range: 18 to 78), with a mean of 15 years of education. Patients were 70% female and 30% male and identified as White/Caucasian (78%), Black/African American (21%), or American Indian (1%). Patients' severity of COVID-19 infection and self-reported emotional, somatic, cognitive, and fatigue symptoms were also gathered to identify concomitant risk factors for insomnia in Long COVID. Patients were then followed to observe the natural trajectory of insomnia complaints in Long COVID, with the Time 2 evaluation a mean of 9 months after the Time 1 evaluation. Results: Seventy-eight percent of Long COVID patients reported insomnia symptoms at Time 1, with 30% reporting Subthreshold Insomnia symptoms (ISI Score = 8-14), 30% reporting Moderate Insomnia symptoms (ISI Score = 15-21), and 18% reporting Severe Clinical Insomnia (ISI Score = 22-28). Severity of acute COVID-19 infection was not correlated with severity of insomnia in Long COVID; however, being non-white (r = 0.24, n = 172, p < 0.01) and having higher self-reported levels of anxiety (r = 0.41, n = 172, p < 0.01), depression (r = 0.52, n = 172, p < 0.01), perceived stress (r = 0.38, n = 172, p < 0.01), somatic symptoms (r = 0.51, n = 172, p < 0.01), cognitive failures, and fatigue were significantly correlated with insomnia symptoms. Insomnia was also significantly correlated with lower global cognitive function (r = 0.51, n = 172, p < 0.01) and lower cognitive flexibility (r = -0.17, n = 172, p < 0.05). There was a statistically significant decrease in reported ISI scores from Time 1 to Time 2 (t = -3.04; p = 0.003); however, ISI mean scores at both Time 1 (ISI Score = 14) and Time 2 (ISI Score = 12) remained in the Subthreshold Insomnia range (ISI score 8-14). Conclusions: Findings suggest that a large majority of Long COVID patients experience insomnia symptoms. Additionally, insomnia symptoms did not dissipate over time in a clinically meaningful way and were highly correlated with reduced global cognitive function, reduced cognitive flexibility, and higher levels of reported mood symptoms, fatigue, somatic symptoms, and experience of cognitive failures. Thus, there is a pressing need for intervention strategies to treat insomnia in Long COVID patients.},
}
@article {pmid40943825,
year = {2025},
author = {Zissler, UM and Poehlmann, T and Gloeckl, R and Ibrahim, S and Klupsch, K and Schneeberger, T and Jarosch, I and Koczulla, AR},
title = {Acute Effects of Osteopathic Treatment in Long COVID-19 Patients with Fatigue Symptoms: A Randomized, Controlled Trial.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943825},
issn = {2077-0383},
abstract = {Background: Persistent fatigue is among the most commonly reported symptoms in patients suffering from post-acute sequelae of SARS-CoV-2 infection (long COVID). Autonomic dysfunction, measurable via heart rate variability, has been implicated as a contributing factor. Osteopathic manipulative treatment is a manual therapeutic approach that targets autonomic balance and may offer a novel intervention for long COVID-related fatigue. Methods: In this single-blind, randomized controlled trial, 42 participants (mean age 51 ± 11 years; fatigue severity score: 31 ± 5 points) with long COVID and persistent fatigue ≥12 weeks post-infection were allocated to either a 45 min standardized osteopathic treatment (n = 21) or a sham-treatment group (n = 21). Heart rate variability was assessed using a 10 min resting electrocardiogram before intervention, immediately after, and again 48 h later. The analysis of heart rate variability encompassed time-domain indices, including the root mean square of successive differences, the standard deviation of normal-to-normal intervals, mean heart rate, and mean RR interval. Additionally, frequency-domain measures such as low-frequency, high-frequency, total power, and the LF/HF ratio were considered. Results: The osteopathy group showed a statistically significant increase in root mean square of successive differences post-treatment (p < 0.01), accompanied by a decrease in the stress index (p < 0.05) and an increase in the mean of the standard deviations of RR intervals (p < 0.05). Significant between-group differences were observed for mean heart rate and mean of RR intervals (p < 0.05). Frequency-domain measures also improved significantly from baseline in the intervention group. Outlier patterns suggest potential subgroup effects, possibly due to underlying dysautonomia. Conclusions: A single session of osteopathic treatment significantly enhanced short-term heart rate variability in long COVID patients with fatigue. These findings highlight the potential role of manual autonomic modulation as a supportive therapy in long COVID management. Further research is needed to assess the long-term effects and optimal treatment frequency of osteopathic manipulative treatment in this population.},
}
@article {pmid40943813,
year = {2025},
author = {Han, E and Hasimbegovic, E and Schönbauer, R and Beitzke, D and Gyöngyösi, M},
title = {Combined Cardiac Arrhythmias Leading to Electrical Chaos Developed in the Convalescent Phase of SARS-CoV-2 Infection: A Case Report and Literature Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943813},
issn = {2077-0383},
support = {KLI 1064-B)//FWF Austrian Science Fund/ ; },
abstract = {Background: Acute SARS-CoV-2 infection may induce cardiac arrhythmias associated with viral myocarditis, which typically disappear in the convalescent phase after healing of the myocardial inflammation. Methods: We report the case of a 37-year-old woman with a childhood history of atrial septal defect repair and stable normofrequent atrial rhythm, who presented two months post-COVID-19 with palpitations and dizziness. Diagnostic evaluation included cardiac magnetic resonance imaging (CMR), 24 h Holter electrocardiogram (ECG) monitoring, and laboratory assessments over a 3-year period. Results: CMR suggested subacute myocarditis, and Holter ECG revealed multiple discernible complex cardiac arrhythmias including atrial bradycardia, intermittent junctional rhythm (JR), atrial fibrillation (AF), and non-sustained ventricular tachycardia. Laboratory results showed a moderate but transient increase in lactate dehydrogenase, persistently mildly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and immunoglobulin A (IgA), with all other cardiac, inflammatory, immunologic, and organ function parameters remaining normal. In spite of chaotic cardiac rhythm with alternating JR, AF, and atrial normofrequent rhythm with frequent blocked supraventricular beats and increasing atrioventricular conduction time, no therapeutic intervention was necessary during follow-up, and a conservative treatment approach was agreed with the patient. Two years post-COVID-19 infection, the patient returned to a normofrequent atrial rhythm with a markedly prolonged PQ time (500 ms) and a different P wave morphology compared to pre-COVID, without other rhythm disturbances. Conclusions: This case demonstrates a rare pattern of post-viral arrhythmias first emerging in the convalescent phase and resolving spontaneously after two years. It underscores the need for long-term rhythm surveillance following COVID-19, even in patients with prior structural heart disease and a stable baseline rhythm.},
}
@article {pmid40943770,
year = {2025},
author = {Var, SR and Maeser, N and Blake, J and Zahs, E and Deep, N and Vasilakos, Z and McKay, J and Johnson, S and Strell, P and Chang, A and Korthas, H and Krishna, V and Narayanan, M and Arju, T and Natera-Rodriguez, DE and Roman, A and Schulz, SJ and Shetty, A and Vernekar, M and Waldron, MA and Person, K and Cheeran, M and Li, L and Low, WC},
title = {Pulmonary and Immune Dysfunction in Pediatric Long COVID: A Case Study Evaluating the Utility of ChatGPT-4 for Analyzing Scientific Articles.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943770},
issn = {2077-0383},
support = {RF1 AG077772/AG/NIA NIH HHS/United States ; AG077772/NH/NIH HHS/United States ; },
abstract = {Coronavirus disease 2019 (COVID-19) in adults is well characterized and associated with multisystem dysfunction. A subset of patients develop post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID), marked by persistent and fluctuating organ system abnormalities. In children, distinct clinical and pathophysiological features of COVID-19 and long COVID are increasingly recognized, though knowledge remains limited relative to adults. The exponential expansion of the COVID-19 literature has made comprehensive appraisal by individual researchers increasingly unfeasible, highlighting the need for new approaches to evidence synthesis. Large language models (LLMs) such as the Generative Pre-trained Transformer (GPT) can process vast amounts of text, offering potential utility in this domain. Earlier versions of GPT, however, have been prone to generating fabricated references or misrepresentations of primary data. To evaluate the potential of more advanced models, we systematically applied GPT-4 to summarize studies on pediatric long COVID published between January 2022 and January 2025. Articles were identified in PubMed, and full-text PDFs were retrieved from publishers. GPT-4-generated summaries were cross-checked against the results sections of the original reports to ensure accuracy before incorporation into a structured review framework. This methodology demonstrates how LLMs may augment traditional literature review by improving efficiency and coverage in rapidly evolving fields, provided that outputs are subjected to rigorous human verification.},
}
@article {pmid40943589,
year = {2025},
author = {Barilli, A and Visigalli, R and Recchia Luciani, G and Crescini, E and Dall'Asta, V and Rotoli, BM},
title = {Baricitinib and Infliximab Mitigate the Endothelial-to-Mesenchymal Transition (EndMT) Induced by Cytokines in HUVECs.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943589},
issn = {1422-0067},
mesh = {Humans ; *Purines/pharmacology ; *Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; *Cytokines/metabolism ; *Epithelial-Mesenchymal Transition/drug effects ; *Infliximab/pharmacology ; *Sulfonamides/pharmacology ; COVID-19/pathology/metabolism ; *Pyrazoles/pharmacology ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Macrophages/metabolism/drug effects/immunology ; COVID-19 Drug Treatment ; Cadherins/metabolism ; Endothelial-Mesenchymal Transition ; Azetidines ; },
abstract = {Endothelial-to-mesenchymal transition (EndMT) is associated with various pathologies including cardiovascular, inflammatory, and fibrotic diseases or neoplasia. Concerning COVID-19, multiple organ dysfunctions and long COVID syndrome are mediated by microvascular damage and, recently, the role of SARS-CoV-2 peptide fragments in the induction of EndMT was demonstrated. Here, we investigated the immune-mediated effects of Spike S1 of SARS-CoV-2 on EndMT and demonstrated that cytokines secreted by S1-activated macrophages, mainly TNFα + IFNγ, also induce the phenotypical switch in HUVECs. In particular, a loss of the typical cobblestone morphology is observed, along with a huge reduction in endothelial adhesion molecules, such as vWF, CD31, and VE-cadherin, and a concomitant acquisition of mesenchymal markers, such as N-cadherin and FSP1 protein. In addition, the combined use of the drug infliximab, targeting TNFα, and baricitinib, an inhibitor of the JAK-STAT pathway, hinders the phenotypical changes by restoring the proper expression of endothelial markers. The protective effect of these drugs is evident not only when they are added to the culture medium together with the trigger, but also when added later, i.e., once EndMT has been started. These findings reinforce the role of COVID-19-associated cytokine storm in endothelial dysfunction and in the onset of the fibrotic process and sustain the clinical relevance of infliximab and baricitinib for the prevention of vascular damage.},
}
@article {pmid40943540,
year = {2025},
author = {Padkao, T and Intakhiao, S and Prakobkaew, N and Buddhisa, S and Teethaisong, Y and Boonla, O and Prasertsri, P},
title = {Anti-Inflammatory and Antioxidant Effects of HIIT in Individuals with Long COVID: Insights into the Potential Role of Triphala.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943540},
issn = {1422-0067},
support = {AHS08/2566 and AHS15/2568//The Faculty of Allied Health Sciences, Burapha University/ ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; *Antioxidants/therapeutic use/pharmacology ; Biomarkers ; *High-Intensity Interval Training/methods ; Inflammation/diagnosis/immunology/therapy/virology ; Interferon-gamma/blood ; Malondialdehyde/blood ; Oxidative Stress/drug effects ; *Plant Extracts/therapeutic use/pharmacology ; *Post-Acute COVID-19 Syndrome/immunology/metabolism/therapy/virology ; SARS-CoV-2/immunology ; Superoxide Dismutase/metabolism ; Tumor Necrosis Factor-alpha/blood ; },
abstract = {Long COVID is characterized by persistent symptoms associated with chronic inflammation and oxidative stress. While high-intensity interval training (HIIT) and supplementation with antioxidants such as Triphala have demonstrated individual therapeutic benefits, their combined effects remain unclear. This study aimed primarily to evaluate the effects of an 8-week HIIT program on markers of inflammation, oxidative stress, and exercise-related symptoms in individuals with long COVID, and secondarily to explore whether Triphala supplementation provided additional benefits. A total of 104 participants (aged 18-59 years) were randomized into three groups-control (placebo), HIIT (cycling for 28 min/day, 3 days/week), and combined (HIIT + Triphala, 1000 mg/day)-for 8 weeks. The biomarkers assessed included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), protein carbonyls, and superoxide dismutase (SOD) activity. Following the intervention, significant reductions in IFN-γ, TNF-α, MDA, protein carbonyls, and rating of perceived exertion were observed in both the HIIT and combined groups (p < 0.05), with no significant differences between the two. SOD activity significantly increased in all groups, including the control group (p < 0.05), with no between-group differences. An 8-week HIIT program appears to be effective in reducing inflammation, oxidative stress, and dyspnea in individuals with long COVID. Triphala supplementation did not provide any additional statistically significant benefit but was safe and well tolerated.},
}
@article {pmid40943354,
year = {2025},
author = {Korobova, ZR and Arsentieva, NA and Lyubimova, NE and Totolian, AA},
title = {Redefining Normal: Cytokine Dysregulation in Long COVID and the Post-Pandemic Healthy Donors.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943354},
issn = {1422-0067},
support = {#225011700915-1//State Task/ ; },
mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; *COVID-19/epidemiology/immunology ; Pandemics ; *Cytokines/blood/immunology ; Aged ; },
abstract = {The COVID-19 pandemic has caused over 7 million deaths, but its legacy extends beyond mortality. SARS-CoV-2 infection induces immune alterations that persist post-recovery, manifesting not only in long COVID (LC) but also in healthy individuals. Cytokines serve as critical orchestrators of these processes. The goal of this study is to investigate post-pandemic immune remodeling through cytokine assessment in both patients with LC and healthy donor, and to compare the post-pandemic population with pre-pandemic controls to find changes in the immune responses and cytokine profiles. A panel of 47 immune mediators (cytokines, chemokines, and growth factors) was measured with the MAGPIX multiplex analysis. LC was characterized by an increase in IL-7, IL-8, IL-17F, IL-18, EGF, FGF-2, PDGF-AA, sCD40L, and MCP-3 and a decrease in IL-4, IL-13, IL-22, IL-27, and FLT-3L. Comparing post-pandemic recovered individuals with pre-pandemic healthy cohort, we saw an upregulation of IL-13 and MCP-3 and a downregulation of MDC, M-CSF, IL-12, and IL-17F. While LC is characterized by persistent immune imbalance-particularly in cytokine networks-our data emphasize the critical need to study healthy donors in both pre- and post-pandemic eras when analyzing and interpreting these changes.},
}
@article {pmid40939695,
year = {2025},
author = {Chadalavada, S and Salih, A and Naderi, H and Rauseo, E and Cooper, J and Duijvenboden, SV and Chahal, AA and Dabbagh, GS and Szabo, L and Khanji, MY and Vargas, JD and Sanghvi, M and Fung, K and Paiva, J and Piechnik, SK and Raman, B and Munroe, PB and Lee, AM and Amir-Khalili, A and Biasiolli, L and Greenwood, JP and Matthews, PM and Bai, W and Neubauer, S and Aung, N and Harvey, NC and Raisi-Estabragh, Z and Petersen, SE},
title = {Prospective electrocardiographic and cardiovascular magnetic resonance alterations in the UK Biobank coronavirus disease 2019 repeat imaging study.},
journal = {Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance},
volume = {27},
number = {2},
pages = {101957},
pmid = {40939695},
issn = {1532-429X},
mesh = {Humans ; Male ; *COVID-19/epidemiology/complications/physiopathology ; Female ; Middle Aged ; *Electrocardiography ; United Kingdom/epidemiology ; Aged ; Prospective Studies ; Case-Control Studies ; SARS-CoV-2 ; *Magnetic Resonance Imaging ; Biological Specimen Banks ; Predictive Value of Tests ; UK Biobank ; },
abstract = {BACKGROUND: Cardiovascular magnetic resonance (CMR) and electrocardiographic (ECG) abnormalities after coronavirus disease 2019 (COVID-19) are widely reported. However, the absence of pre-infection assessments limits causal inference from these studies. This study aims to compare interval change in CMR and ECG measures in participants with incident COVID-19 and matched uninfected controls in UK Biobank.<br><br>METHODS: UK Biobank participants with documented COVID-19 who had CMR and ECG performed before the pandemic were invited for repeat assessment, along with uninfected participants matched on age, sex, ethnicity, location, and date of baseline imaging. Automated pipelines were used to extract ECG phenotypes and CMR measures of cardiac structure and function, aortic distensibility, aortic flow, and myocardial native T1. Logistic regression was used to examine associations of baseline metrics with incident COVID-19. Standardized residual approach was used to compare the degree of interval change in CMR and ECG metrics between cases and controls.<br><br>RESULTS: We analyzed 2092 participants (1079 cases&#xa0;and&#xa0;1013 controls) with average age of 60 &#xb1; 7 years. 47.1% were male. There was 3.2 &#xb1; 1.5 years between pre- and post-infection assessments. 3.6% of cases were hospitalized. Lower baseline left ventricular ejection fraction and worse longitudinal, circumferential, and radial strain were associated with higher risk of incident COVID-19. There were no significant differences in interval change of any CMR or ECG metric between cases and controls.<br><br>CONCLUSION: While pre-existing cardiovascular abnormalities are linked to higher risk of COVID-19, exposure to infection does not alter interval change of highly sensitive CMR and ECG indicators of cardiovascular health.},
}
@article {pmid40939689,
year = {2025},
author = {Yang, X and Shen, Y and Tang, B and Zhu, J and Wang, B and Wang, Q and Tian, W and Wuchty, S and Zhang, Z and Liang, Z and Dong, Y},
title = {Multi-Omics Blood Atlas Reveals Host Immune Response Features of Immunocompromised Populations Following SARS-CoV-2 Infection.},
journal = {Molecular &amp; cellular proteomics : MCP},
volume = {24},
number = {10},
pages = {101068},
pmid = {40939689},
issn = {1535-9484},
mesh = {Humans ; *COVID-19/immunology/blood/genetics ; *SARS-CoV-2/immunology ; Proteomics/methods ; *Immunocompromised Host/immunology ; Female ; Male ; Middle Aged ; Transcriptome ; Proteome ; Protein Interaction Maps ; Aged ; Hematologic Neoplasms/immunology ; Adult ; Multiomics ; },
abstract = {The dysregulation of human genes and proteins following SARS-CoV-2 infection significantly impacts the clinical symptoms and prognosis of COVID-19, particularly in immunocompromised individuals such as patients with hematological tumors. Despite this, a comprehensive multi-omics understanding of human host immune responses remains incomplete. Here, we conducted a multi-omics analysis of 89 peripheral blood samples (RNA sequencing) and 98 serum samples (proteome mass spectrometry) from 52 patients with COVID-19, including patients with hematological tumors and non-tumor individuals. By integrating transcriptomic, proteomic, and interactome data, we compared differentially expressed genes (DEGs) and proteins (DEPs) across infection stages and clinical outcomes to gain insights into the mechanisms of SARS-CoV-2 infection. Our analysis revealed distinct and overlapping transcriptomic and proteomic responses to SARS-CoV-2 infection. DEGs were predominantly associated with innate immune responses and viral processes, while DEPs were linked to actin cytoskeleton organization and protein kinase regulation. Notably, DEGs and DEPs often exhibited opposing regulatory patterns, suggesting post-transcriptional and post-translational mechanisms. Tumor patients showed more severe proteomic perturbations, with a higher proportion of DEPs functioning as key hub proteins in cellular networks. Network-based drug repositioning identified potential therapeutic targets, including HSPA8, SRC, STAT1, APOE, and APP. Clinical analysis indicated that patients with long COVID experienced more severe coagulation abnormalities, immunosuppression, and myocardial injury, while acutely deceased patients exhibited abnormally activated immune responses. Our study provides a comprehensive resource for understanding the molecular mechanisms of SARS-CoV-2 infection in patients with hematological tumors. By integrating multi-omics data, we highlight the importance of proteomic changes in disease progression and identify potential therapeutic targets for COVID-19 and long COVID.},
}
@article {pmid40939145,
year = {2025},
author = {},
title = {Correction to "Symptoms and Risk Factors for Long Covid: A Cross-Sectional Study In Primary Care".},
journal = {Journal of medical virology},
volume = {97},
number = {9},
pages = {e70609},
doi = {10.1002/jmv.70609},
pmid = {40939145},
issn = {1096-9071},
}
@article {pmid40938404,
year = {2026},
author = {Paranhos, ACM and Dias, ARN and Mendes, EAR and Paixão, EVA and Silva, SFVS and Dos Santos, LPM and Koury, GVH and Domingues, MM and Quaresma, JAS and da Silva Souza, G and Falcão, LFM},
title = {Persistent olfactory dysfunction as an indicator of cognitive impairment in long COVID-19 syndrome: implications for monitoring and rehabilitation.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {276},
number = {1},
pages = {267-274},
pmid = {40938404},
issn = {1433-8491},
support = {Funda&#xe7;&#xe3;o Amaz&#xf4;nia Paraense de Amparo &#xe0; Pesquisa//Funda&#xe7;&#xe3;o Amaz&#xf4;nia Paraense de Amparo &#xe0; Pesquisa/ ; Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; SECTET//SECTET/ ; },
mesh = {Humans ; Female ; *COVID-19/complications/rehabilitation/epidemiology ; Male ; Middle Aged ; Cross-Sectional Studies ; *Olfaction Disorders/rehabilitation/etiology/epidemiology/diagnosis/physiopathology ; Adult ; *Cognitive Dysfunction/rehabilitation/etiology/diagnosis/epidemiology/physiopathology ; *Anosmia/etiology ; Brazil/epidemiology ; Aged ; Severity of Illness Index ; },
abstract = {BACKGROUND: Persistent olfactory dysfunction (OD) and cognitive impairment are among the most frequently reported sequelae of long term infection with SARS-CoV-2 (long COVID-19). However, the association between these conditions remains unclear. This study investigated the correlation between OD and cognitive impairment in patients recovering from COVID-19 to identify the implications for therapeutic and rehabilitation strategies.<br><br>MATERIALS AND METHODS: A cross-sectional study of adult patients diagnosed with long COVID was conducted at a healthcare centre in Brazil. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Centre (CCCRC) test, and cognitive performance was evaluated using the Montreal Cognitive Assessment (MoCA). Statistical analyses included odds ratios (OR) and linear regression to explore the association between OD severity and cognitive scores, adjusting for potential confounders such as age, sex, and comorbidities.<br><br>RESULTS: A total of 241 patients (age: 48.60&#x2009;&#xb1;&#x2009;12.68 years; 73% female) were included. Cognitive impairment (MoCA&#x2009;<&#x2009;23) was present in 64% of the participants. OD was identified in 92% of the patients and ranged from mild to anosmia. Linear regression analysis showed a weak yet statistically significant correlation between the CCCRC and MoCA scores (R&#x2009;=&#x2009;0.14, p&#x2009;=&#x2009;0.02). An OR of 2.87 (95% CI: 1.57-5.25, p&#x2009;=&#x2009;0.00) indicated higher odds of cognitive impairment in patients with severe OD.<br><br>DISCUSSION: This study supports the hypothesis that there is a weak yet significant association between OD and cognitive impairment in patients with long COVID. These findings underscore the importance of early screening for olfactory dysfunction as a potential marker of cognitive monitoring and the need for intervention in this population.},
}
@article {pmid40937423,
year = {2025},
author = {Altermatt, A and Wilkinson, AL and Heath, K and Jin, D and Nguyen, T and Thomas, AJ and Ke, T and Zhang, Y and Ryan, RE and Gibbs, L and Pedrana, A and Lusher, D and Fletcher-Lartey, S and Stoové, M and Gibney, KB and Hellard, M},
title = {Well-being among people with long and short COVID: a serial cross-sectional study in Victoria, Australia.},
journal = {BMJ public health},
volume = {3},
number = {2},
pages = {e002062},
pmid = {40937423},
issn = {2753-4294},
abstract = {BACKGROUND: It is critical to disseminate all evidence on long COVID's impact on people's lives to inform policy and practice. We aimed to assess five measures of well-being, before and after SARS-CoV-2 infection between people with long COVID (defined as symptoms lasting more than 1 month) and people with short COVID (defined as symptoms resolving within 1 month).<br><br>METHODS: Participants from the Optimise Study, a longitudinal cohort study in Victoria, Australia (September 2020-August 2022), had self-reported history of SARS-CoV-2 infection and self-reported long COVID status. Serial cross-sectional analysis compared participants with long and short COVID on Personal Well-being Index, number of COVID-19-like symptoms experienced, number of days exercised and frequency of experiencing positive and negative emotions.<br><br>RESULTS: 217 participants were included, aged 20-86 years (median age 43, IQR: 31-57), 75%&#x2009;women. Compared with those with short COVID, participants with long COVID had lower well-being before (mean difference (MD)=-8.3, 95%&#x2009;CI (-14.7, -2.0), p-adjusted=0.07), during (MD=-10.3, 95%&#x2009;CI (-16.5, -4.0), p-adjusted=0.03) and after (MD=-9.91, 95%&#x2009;CI (-16.71, -3.11), p-adjusted=0.05) infection and experienced more COVID-19-like symptoms during infection (MD=1.72 (0.72, 2.72), p-adjusted=0.03). In December 2022, 71% (40/56) reported difficulty performing tasks in the past 4&#x2009;weeks.<br><br>CONCLUSION: On average, we observed lower well-being among participants with long COVID, including before SARS-CoV-2 infection, suggesting an underlying difference in well-being between groups. Long COVID continued to impact physical functioning, but ongoing changes were not detected by personal well-being scales.},
}
@article {pmid40934950,
year = {2025},
author = {Steenblock, C and Walther, R and Kok, Y and Mavberg, P and Yaman, M and Handgretinger, R and Castillo-Aleman, YM and Al Karam, M and Bornstein, SR},
title = {Single-Center Study of Therapeutic Apheresis in 24 Male Patients from the MENA Region: Reduction of Lipids, Inflammatory Markers, Autoantibodies, and Implications for Fatigue, Genetics, and Aging.},
journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme},
volume = {57},
number = {11},
pages = {646-652},
doi = {10.1055/a-2678-7739},
pmid = {40934950},
issn = {1439-4286},
mesh = {Humans ; Male ; *Autoantibodies/blood ; Middle Aged ; Adult ; Biomarkers/blood ; *Blood Component Removal/methods ; *Lipids/blood ; *Fatigue/therapy/blood/genetics ; *Aging/blood/genetics ; *COVID-19/blood/therapy ; Middle East/epidemiology ; Inflammation/blood ; SARS-CoV-2 ; Aged ; },
abstract = {Cardiovascular and metabolic disorders, particularly diabetes and obesity, are highly prevalent in the Middle East and North Africa (MENA) region, exhibiting some of the highest global incidence rates. These conditions significantly increase the severity of infectious diseases, notably COVID-19, leading to a rise in long-COVID cases among affected individuals. Furthermore, the MENA region's extreme temperatures exacerbate cardiovascular issues by elevating heart rates and blood pressure, increasing dehydration and blood viscosity. Extracorporeal therapies, such as apheresis, effectively reduces plasma lipids and inflammatory markers. Furthermore, apheresis has shown promise in reducing autoantibodies associated to long-COVID. Our previous research indicated that apheresis alleviates symptoms in patients with long-COVID and chronic fatigue syndrome. In this study, we treated 24 male patients from the MENA region suffering from chronic fatigue and/or different metabolic diseases such as diabetes, dyslipidemia, or obesity, using double filtration plasmapheresis. Comprehensive plasma analyses were performed before and after apheresis to assess lipid profiles, inflammatory markers, and autoantibodies, revealing significant changes following the procedure. Genetic analyses on a subgroup of the patients showed no mutations in the LDLR, APOB, APOE, PCSK9, LIPA, and LDLRAP1 genes known to be associated with predispositions to monogenic lipid disorders. However, all patients in this subgroup demonstrated an intermediate to high likelihood that their elevated lipid levels have a polygenic basis. These findings suggest that implementing apheresis in the MENA region could significantly improve health outcomes and life expectancy for affected individuals.},
}
@article {pmid40934937,
year = {2025},
author = {Wilhelm, F and Cadamuro, J and Mink, S},
title = {Autoantibodies in long COVID: a systematic review.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00411-6},
pmid = {40934937},
issn = {1474-4457},
abstract = {Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers. This systematic review synthesises current evidence on the association between autoantibodies and long COVID, with the goal of evaluating their prognostic and diagnostic utility. Studies published in the PubMed and MEDLINE databases between Jan 1, 2020, and June 10, 2025, were considered. Study selection and quality assessment were done independently by two researchers. Of the 1113 publications screened, 44 studies met the inclusion criteria, with a total of 7571 participants, including 3372 individuals with long COVID. 31 (71%) studies reported an association between autoantibodies and long COVID; however, there was substantial heterogeneity in study design, type and timing of antibody measurements, and long COVID definitions. Several autoantibodies have been associated with long COVID occurrence, symptoms, and severity. Antinuclear antibodies, and autoantibodies targeting G protein-coupled receptors and chemokines, have emerged as potential biomarkers for aiding in the diagnosis, prognosis, and assessment of disease severity in long COVID. However, larger studies are needed to confirm the diagnostic and prognostic utility of these autoantibodies in the context of long COVID.},
}
@article {pmid40934019,
year = {2025},
author = {Gutiérrez-Martínez, L and Reynolds, WC and Abril, I and González-Irizarry, G and Ortiz-Acosta, P and Mullington, JM and Rosand, J and Tanzi, RE and Arnold, SE and Guzmán-Vélez, E},
title = {Sleep quality and efficiency in adults with post-acute sequelae of COVID-19.},
journal = {Sleep advances : a journal of the Sleep Research Society},
volume = {6},
number = {3},
pages = {zpaf051},
pmid = {40934019},
issn = {2632-5012},
abstract = {STUDY OBJECTIVES: Sleep disruptions are associated with adverse mental and physical health outcomes. Individuals with post-acute sequelae of COVID-19 (PASC) commonly report worsened sleep. This study examined sleep quality and efficiency and their associations with neuropsychiatric symptoms and fatigue in non-hospitalized individuals with PASC.<br><br>METHODS: Sixty-one participants (73.8 percent female; - age&#x2009;=&#x2009;45.4) who reported being infected with COVID-19&#x2009;&#x2265;&#x2009;2&#xa0;months before enrollment, non-hospitalized, and experiencing &#x2265;3 symptoms since infection were eligible. The Pittsburgh Sleep Quality Index was used to measure self-reported sleep quality, and the Fitbit Charge-4 to assess sleep efficiency. Participants completed the Beck Anxiety Index, Beck Depression Index, Post-Traumatic Stress Disorder-Checklist Civilian Version, and the Fatigue Severity Scale. We conducted multivariable linear regressions to examine associations controlling for age, sex, time since first COVID-19 infection, pre-COVID sleep disorders, and sleep aids.<br><br>RESULTS: Pittsburgh Sleep Quality Index scores were not associated with objective sleep efficiency. Nearly 97 percent of PASC participants reported poor sleep quality, 85 percent indicated that sleep difficulties interfered with their daily functioning, and 93.9 percent achieved optimal sleep efficiency. Higher Beck Depression Index scores were linked to worse sleep quality, while Beck Anxiety Index, Post-Traumatic Stress Disorder-Checklist Civilian Version, and Fatigue Severity Scale scores were not. However, Beck Anxiety Index and Fatigue Severity Scale scores were related to distinct Pittsburgh Sleep Quality Index components. None were associated with sleep efficiency.<br><br>CONCLUSION: Individuals with PASC experience significant sleep difficulties impacting daily functioning. Although they showed adequate sleep efficiency, most participants perceived their sleep as inefficient, which correlated with worse depressive symptoms. Therefore, sleep is a modifiable factor that could enhance the quality of life for patients with PASC.},
}
@article {pmid40933864,
year = {2025},
author = {Becker, JH and Li, J and Lin, JJ and Federman, A and Bagiella, E and Kale, MS and Fierer, D and Bartram, L and Wisnivesky, JP},
title = {Neurocognitive trajectories in long COVID: Evidence from longitudinal analyses.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {48},
number = {},
pages = {101093},
pmid = {40933864},
issn = {2666-3546},
abstract = {BACKGROUND: Patients frequently report symptoms of cognitive impairment or "brain fog" after acute COVID-19 infection, but the trajectory of these symptoms over time has yet to be determined. We assessed cognitive function over a 42-month period after acute SARS-CoV-2 infection and identified factors associated with the trajectory of cognitive function over this period.<br><br>METHODS: We analyzed data from participants in the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort study of adults followed after acute SARS-CoV-2 infection of any severity. Participants were identified from a list of all patients with COVID-19 who received care at an MSHS facility in New York, recruited beginning April 2020 and followed through January 2024. Cognition was assessed using well-validated in-person measures of attention, working memory, processing speed, executive functioning, language, and memory. We used linear mixed models to investigate the relationships between cognitive scores and time. We also assessed factors (including race, ethnicity, site of acute COVID-19 care, fatigue, depression, anxiety, body mass index, medical comorbidities, and COVID-19 vaccination) that may influence changes in cognitive scores over time.<br><br>FINDINGS: We analyzed data from 1553 participants (median age 53 years, 63&#xa0;% female, 17&#xa0;% Black, 21&#xa0;% Hispanic). In adjusted analyses, scores from cognitive measures of attention, working memory, processing speed, executive functions, and verbal learning and memory improved progressively through 42 months post-COVID. However, despite the improvements, on average, measures of processing speed and executive functioning remained &#x2265;1 standard deviation below the normative mean. Having a body mass index of <25&#xa0;kg/m[2] was predictive of a greater improvement in cognitive scores.<br><br>INTERPRETATION: While cognitive impairment occurring after COVID-19 improved over time in most domains, processing speed and executive functioning remained below the normal range. The cognitive health burden of Long COVID is therefore significant and lasting. Future studies should examine interventions to support rapid recovery, as well as dynamic risk prediction models to determine factors that may impact cognitive recovery longer term.},
}
@article {pmid40933446,
year = {2025},
author = {Lee, SP and Kang, SY},
title = {Clinical outcomes of persistent cough following coronavirus disease 2019 infection: A 1-year retrospective cohort study.},
journal = {Asia Pacific allergy},
volume = {15},
number = {3},
pages = {186-191},
pmid = {40933446},
issn = {2233-8276},
abstract = {BACKGROUND: Cough is one of the multiple prolonged symptoms observed in patients who had coronavirus disease 2019 (COVID-19) infection.<br><br>OBJECTIVE: We assessed the clinical outcomes and identified factors contributing to cough persistence in patients post-COVID-19.<br><br>METHODS: This retrospective cohort study included adults who visited a specialist cough clinic between 2022 and 2023. All participants underwent systematic investigation and treatment for persistent cough. Cough persistence was assessed at the 2- and 12-month follow-ups. Participants were classified as having persistent cough if they had a current troublesome cough at the 2- and 12-month follow-ups, and a cough severity visual analog scale (VAS) score change below 30.<br><br>RESULTS: Sixty-six patients (mean age 48.7 years; 72.7% women) were analyzed and divided into 2 groups: persistent cough (33.3%) and remitted cough (66.7%). The persistent cough group had a significantly higher prevalence of abnormal laryngeal sensation, sputum production, breathing difficulty, and airway eosinophilia; their VAS score changes at 2 months were also lower. Multivariable analyses indicated associations between persistent cough at 1 year and factors such as airway eosinophilia (adjusted odds ratio [aOR], 6.78), abnormal laryngeal sensation (aOR, 6.42), and low cough VAS reduction (aOR, 1.05).<br><br>CONCLUSION: Persistent cough remained a significant issue for one-third of the patients after COVID-19. The clinical features commonly observed in chronic cough were also present in those who have experienced COVID-19, which contributed to prolonged cough. These findings underscore the need for systematic assessment and tailored treatment strategies to effectively manage persistent cough in patients post-COVID-19.},
}
@article {pmid40932810,
year = {2025},
author = {Cooper, E and Lound, A and Jones, K and Bruton, J and Day, S and Atchison, CJ and Eccles, C and Piper, A and Cooke, GS and Chadeau-Hyam, M and Elliott, P and Ward, H},
title = {Challenges of Inclusion: A Population-Based Interview Study of Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70428},
pmid = {40932810},
issn = {1369-7625},
support = {//This study is independent research funded by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI): REACT-GE (Genomics England) (UKRI MC_PC_20049) and REACT-LC (Long Covid) (COV-LT-0040). The REACT-1 and REACT-2 studies were funded by the Department of Health and Social Care in England (DHSC). We also acknowledge support from the NIHR Imperial Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of DHSC, NIHR or UKRI./ ; },
mesh = {Qualitative Research ; Interviews as Topic ; *Post-Acute COVID-19 Syndrome/psychology ; England/epidemiology ; *COVID-19/epidemiology/psychology ; Prevalence ; *Self-Management/psychology ; Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Health Services Accessibility/statistics &amp; numerical data ; Social Support/psychology ; Social Inclusion ; *Cost of Illness ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: People with long Covid report a wide range of symptoms and inconsistent responses when seeking clinical diagnosis and support. Much of the qualitative research on long Covid has been based on people attending specialist clinical services or who have accessed support groups. We aimed to understand the varied experiences of persistent symptoms following Covid-19 and the impact on the lives of people affected.<br><br>METHODS: Qualitative interview study nested within the large, community-based REal-time Assessment of Community Transmission (REACT) study in England. Participants reporting persistent symptoms following Covid-19 were asked for consent to be contacted about a follow-up interview. We then purposively sampled by age, gender, ethnicity and symptom severity and conducted 60 interviews. Analysis was carried out using a reflexive thematic analysis approach.<br><br>RESULTS: Participants were an ethnically diverse group aged between 18 and 80 years who reported symptoms following Covid-19 for between a few months and more than 2 years. Many had not accessed clinical care or specific long Covid support, and some did not identify with the category of long Covid, rendering their experiences largely invisible. Participants highlighted the ways in which they self-manage symptoms within this context, and the varied burden of coping with ongoing health problems.<br><br>CONCLUSION: This diverse sample of people with long Covid report a range of challenges managing this emerging and contested condition, with uncertainty affecting their own understanding and the validation they receive from professionals, family and friends. These challenges intersect with others, such as racism, and are compounded by a lack of specific resources for long Covid as well as over-stretched health services in the United Kingdom. Nevertheless, people report a variety of strategies in managing their symptoms, seeking information and support from a range of sources.<br><br>Study design, analysis and drafting of paper informed by Patient Advisory Group.},
}
@article {pmid40932654,
year = {2025},
author = {Gustavsson, E and Johnson, E and Levi, R},
title = {Towards a Less Ideal Theory About Well-being-The Case of Post COVID Condition.},
journal = {Journal of bioethical inquiry},
volume = {},
number = {},
pages = {},
pmid = {40932654},
issn = {1872-4353},
support = {Dnr 2021-01245//Vetenskapsr&#xe5;det/ ; },
abstract = {Post COVID-19 Condition (PCC) is a complex condition presenting significant challenges for patients. Individuals suffering from severe PCC are often assessed in rehabilitation medicine departments or specialized post-COVID centres, where their condition is evaluated using the International Classification of Functioning, Disability and Health (ICF). The ICF framework primarily focuses on functional impairments, disabilities, and restrictions in participation, with an emphasis on the concept of "functioning." However, a critical question remains: how does this notion of functioning relate to the well-being of these individuals? This paper explores this issue by examining three fictionalized but typical case studies of PCC patients in relation to two distinct theoretical approaches. First, we engage with theories about well-being from the philosophy of well-being emphasizing the individual's perspective. Second, we explore relational approaches in bioethics and their theoretical underpinnings, which emphasize how people are situated, considering context and relations rather than purely individual conditions. The paper highlights the potential tensions between these approaches while arguing that a more comprehensive understanding of well-being can emerge by integrating insights from both traditions. Through the examination of PCC patient cases, we propose that well-being can be better understood when approached from multiple angles, enriching the understanding of patient outcomes in rehabilitation medicine.},
}
@article {pmid40932646,
year = {2025},
author = {Crevenna, R and Keilani, M},
title = {Correction to: Authors' response to the letter to the editor 'Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue'.},
journal = {Wiener klinische Wochenschrift},
volume = {137},
number = {21-22},
pages = {739},
doi = {10.1007/s00508-025-02603-w},
pmid = {40932646},
issn = {1613-7671},
}
@article {pmid40930270,
year = {2025},
author = {Walker, TA and Kohler, JZ and Haddad, MM},
title = {Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management.},
journal = {Brain, behavior, and immunity},
volume = {130},
number = {},
pages = {106108},
doi = {10.1016/j.bbi.2025.106108},
pmid = {40930270},
issn = {1090-2139},
}
@article {pmid40927706,
year = {2025},
author = {Sandoval, MN and Moore, LW and Huang, HJ and Graviss, EA},
title = {Long COVID risk factors and outcomes among solid organ transplant recipients: a retrospective cohort study.},
journal = {Frontiers in surgery},
volume = {12},
number = {},
pages = {1602167},
pmid = {40927706},
issn = {2296-875X},
abstract = {BACKGROUND: Solid organ transplant (SOT) recipients are not only at increased risk of morbidity and mortality due to acute COVID-19 but may also experience poor long-term outcomes due to post-acute COVID-19 syndromes, including long COVID.<br><br>METHODS: This retrospective, registry-based chart review evaluated graft failure and mortality among SOT recipients diagnosed with COVID-19 at a large, urban transplant center in Houston, Texas, USA. Patient populations were analyzed separately according to their long COVID status at the time of transplant to preserve the temporal relationship between the exposure (long COVID) and the outcome (graft failure or mortality).<br><br>RESULTS: In total, 146 (5%, 146/3,202) patients were diagnosed with long COVID, 443 (14%, 443/3,202) patients expired during the study period, and 202 (6%, 202/3,202) were diagnosed with graft failure. Overall, patients with long COVID were older, had an increased comorbidity burden, and were more likely to be lung, heart, or heart-lung recipients compared with those who were not diagnosed with long COVID. Long COVID was not significantly associated with death or graft failure in this study population, though relationships varied across subpopulations.<br><br>CONCLUSIONS: The observed differences between patients diagnosed with COVID-19 and long COVID before and after transplant warrant additional studies as the proportion of people with some SARS-CoV-2 infection history approaches 90%. Future investigations may prioritize longitudinal follow-up of long COVID patients diagnosed before or after transplant to determine specific etiologies of long-term morbidity and mortality.},
}
@article {pmid40927340,
year = {2025},
author = {Leitner, M and Paletta, L and Leal-Garcia, M and Fellner, M and Koini, M},
title = {A tablet-based intervention study to alleviate cognitive and psychological symptoms in patients with post-Covid-19 condition.},
journal = {Frontiers in psychology},
volume = {16},
number = {},
pages = {1582742},
pmid = {40927340},
issn = {1664-1078},
abstract = {BACKGROUND: Cognitive impairment and psychological complaints are among the most common consequences for patients suffering from Post-Covid-19 condition (PCC). As there are limited training options available, this study examined a longitudinal tablet-based training program addressing cognitive and psychological symptoms.<br><br>METHODS: Forty individuals aged between 36 and 71 years (M = 49.85, SD = 8.63; 80% female) were randomly assigned to either an intervention group (n = 20) or a waitlist control group (n = 20). The intervention group received a three-month tablet-based training program involving cognitive exercises, relaxation techniques, and physiotherapy exercises. Additionally, both groups underwent a thorough neuropsychological assessment (attention, memory, executive functions, word fluency, subjective cognitive complaints, fatigue, depression, anxiety, and quality of life) before the training, after 3 months of training, and after 6 months in order to assess long-term effects.<br><br>RESULTS: Pre-post comparisons revealed that individuals assigned to the intervention group (n = 18 after dropout), as compared to the control group (n = 16 after dropout), showed a reduction in subjective cognitive complaints (p < 0.001) as well as in depressive symptoms (p < 0.001). Additionally, their MoCA Memory Index Score remained stable (p = 0.496), while it declined significantly in the wait-list control group (p = 0.008). However, the training had no effect on the other domains assessed and not all training-related effects were stable over time. Finally, a higher number of post-Covid symptoms was negatively correlated with attention and memory capabilities (all p < 0.05), with a longer disease duration further amplifying the negative impact of post-Covid symptoms on memory performance.<br><br>CONCLUSION: Tablet-based training programs can help improve subjective complaints, depressive symptoms, and memory and may serve as an additional therapy option. Further studies are needed to investigate the stability of these effects.},
}
@article {pmid40926885,
year = {2025},
author = {Ferreira, LGJ and da Silva Almeida, I and Costa, RR and Roriz, GV and Geremia, JM and Durigan, JLQ and Marqueti, RC},
title = {Long COVID-19 alters muscle architecture and muscle-tendon force transmission: a one-year longitudinal study.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1641046},
pmid = {40926885},
issn = {1664-042X},
abstract = {INTRODUCTION: There are limited studies on the long-term effects of COVID-19 on skeletal muscle morphology and architecture. Therefore, this study aims to address this gap by assessing the effects of prior COVID-19 infection on quadriceps muscle architecture and tendon-aponeurosis complex (TAC) properties over a one-year period, comparing three cohorts: individuals with moderate COVID-19, individuals with severe COVID-19, and a healthy control group.<br><br>METHODS: Seventy participants were included in the study and allocated to three groups: moderate COVID-19 (n = 22), severe COVID-19 (n = 18), and control (n = 30). Four assessments were conducted over 1 year for the COVID groups. Maximal voluntary isometric (MVIC) knee extension contractions were performed on an isometric dynamometer, with simultaneous ultrasound imaging of the vastus lateralis (VL) and rectus femoris (RF) muscles. Fascicle length (FL) and pennation angle (PA) were obtained at rest and during MVIC, along with TAC displacement. Generalized Estimating Equation models were used to evaluate muscle variables, with "group" and "time" as factors. The model fit was adjusted, with 'torque' as a covariate.<br><br>RESULTS: Regarding muscle architecture, FL was greater in the severe COVID-19 group during early post-infection assessments for the RF at rest (p = 0.043). Additionally, both COVID-19 groups exhibited longer VL fascicles compared to controls (p = 0.032). TAC displacement was reduced in the severe COVID-19 group (RF: p = 0.008; VL: p = 0.047) compared to control. TAC stiffness did not differ between groups (p = 0.517), but torque production demonstrated an effect on this variable (p = 0.001). Both COVID-19 groups presented reduced PA for the VL at rest (p = 0.012) compared to control. Additionally, torque played a crucial role in influencing PA in both muscles, at rest and during contraction.<br><br>CONCLUSION: Participants with severe COVID-19 exhibited alterations in muscle architecture, which may contribute to persistent muscular weakness even one-year post-infection. The findings underscore the potential role of muscle strength, particularly the impact of torque on TAC stiffness and PA across all groups. Long COVID-19 rehabilitation and exercise physiologists should prioritize quadriceps strengthening strategies to restore muscle architecture and optimize force transmission.},
}
@article {pmid40926879,
year = {2025},
author = {Pienkos, S and Swank, Z and Hamlin, RE and Rao, M and Grant, P and Bonilla, H and Jacobson, K and Jagannathan, P and Singh, U and Walt, DR and Subramanian, A and Blish, C},
title = {Single-Cell and Plasma Proteomics Do Not Differentiate Patients With and Without SARS-CoV-2 Antigenemia in Convalescence in a Cohort of 100 Patients.},
journal = {Open forum infectious diseases},
volume = {12},
number = {9},
pages = {ofaf515},
pmid = {40926879},
issn = {2328-8957},
support = {T32 HL129970/HL/NHLBI NIH HHS/United States ; },
abstract = {Plasma samples obtained approximately 3 (n = 100) and 12 months (n = 78) after acute SARS-CoV-2 infection were tested for S1, spike, and N antigens. There were no significant differences in plasma proteins or single-cell protein expression levels on immune cells between those with and without plasma antigen detected.},
}
@article {pmid40924654,
year = {2026},
author = {Fazekas, C and Goswami, N and Matzer, F and Avian, A and Lodron, J and Rijksen, M and Hanfstingl, B and Kavcic, V and Groselj-Strele, A and Sourij, H and Kessler, HH and Stelzl, E and Voegel, CD and Binz, TM and Schmid-Zalaudek, K and Wittmann, A and Pilz, S},
title = {Perceived Chronic Stress prior to SARS-CoV-2 Infection Predicts Ongoing Symptomatic COVID-19: A Prospective Cohort Study.},
journal = {Psychotherapy and psychosomatics},
volume = {95},
number = {1},
pages = {76-87},
pmid = {40924654},
issn = {1423-0348},
mesh = {Humans ; *COVID-19/psychology/epidemiology ; Female ; Male ; *Stress, Psychological/psychology/epidemiology/complications ; Middle Aged ; Prospective Studies ; Adult ; Hydrocortisone/analysis/metabolism ; Chronic Disease ; Hair/chemistry ; Risk Factors ; SARS-CoV-2 ; },
abstract = {UNLABELLED: <p>Introduction: Understanding chronic stress as a potential risk factor for COVID-19 progression could inform public health measures and personalized preventive interventions. Therefore, we investigated the influence of chronic stress prior to SARS-CoV-2 infection on symptom persistence 1 month after COVID-19 onset.<br><br>METHODS: The participants of this prospective cohort study named "StressLoC" were adults with COVID-19 who had tested positive for SARS-CoV-2 infection within the last 7 days. Pre-existing perceived chronic stress assessed by the Perceived Stress Scale (PSS-10) was the primary predictor. The number of stressful life events and hair cortisol concentration served as additional measures of pre-existing chronic stress. The main outcome was examined using the Long COVID Symptom and Impact Tool. It was defined as the presence of any new and impactful COVID-19-related symptom at month 1 after inclusion. Accordingly, participants were assigned to either the ongoing symptomatic COVID-19 group (OSC-G) or control group.<br><br>RESULTS: The study cohort comprised 288 participants (73.3% female), with a median age of 46 years (IQR 35-56). A total of 210 participants (72.9%) were categorized as OSC-G. Multivariate logistic regression showed that allocation to OSC-G was predicted by perceived chronic stress in the month prior to COVID-19 (OR: 1.08, 95% CI: 1.03-1.14; p = 0.002) and the number of pre-existing symptoms (OR: 1.08, 95% CI: 1.03-1.13; p = 0.001). The number of stressful life events and hair cortisol concentration did not predict OSC-G allocation.<br><br>CONCLUSIONS: Results suggest that higher levels of pre-existing perceived chronic stress increase the odds of developing ongoing symptomatic COVID-19. </p>.},
}
@article {pmid40924481,
year = {2025},
author = {Gabernet, G and Maciuch, J and Gygi, JP and Moore, JF and Hoch, A and Syphurs, C and Chu, T and Doni Jayavelu, N and Corry, DB and Kheradmand, F and Baden, LR and Sekaly, RP and McComsey, GA and Haddad, EK and Cairns, CB and Rouphael, N and Fernandez-Sesma, A and Simon, V and Metcalf, JP and Agudelo Higuita, NI and Hough, CL and Messer, WB and Davis, MM and Nadeau, KC and Pulendran, B and Kraft, M and Bime, C and Reed, EF and Schaenman, J and Erle, DJ and Calfee, CS and Atkinson, MA and Brakenridge, SC and Melamed, E and Shaw, AC and Hafler, DA and Augustine, AD and Becker, PM and Ozonoff, A and Bosinger, SE and Eckalbar, W and Maecker, HT and Kim-Schulze, S and Steen, H and Krammer, F and Westendorf, K and , and Peters, B and Fourati, S and Altman, MC and Levy, O and Smolen, KK and Montgomery, RR and Diray-Arce, J and Kleinstein, SH and Guan, L and Ehrlich, LI},
title = {A multiomics recovery factor predicts long COVID in the IMPACC study.},
journal = {The Journal of clinical investigation},
volume = {135},
number = {21},
pages = {},
pmid = {40924481},
issn = {1558-8238},
support = {U19 AI090023/AI/NIAID NIH HHS/United States ; U19 AI118608/AI/NIAID NIH HHS/United States ; U01 AI167892/AI/NIAID NIH HHS/United States ; U54 AI142766/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; U19 AI062629/AI/NIAID NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; U19 AI128910/AI/NIAID NIH HHS/United States ; R01 AI104870/AI/NIAID NIH HHS/United States ; T32 DA018926/DA/NIDA NIH HHS/United States ; U19 AI167891/AI/NIAID NIH HHS/United States ; U19 AI167903/AI/NIAID NIH HHS/United States ; U19 AI125357/AI/NIAID NIH HHS/United States ; R01 AI145835/AI/NIAID NIH HHS/United States ; U19 AI128913/AI/NIAID NIH HHS/United States ; R01 AI132774/AI/NIAID NIH HHS/United States ; R01 AI122220/AI/NIAID NIH HHS/United States ; U19 AI077439/AI/NIAID NIH HHS/United States ; R01 AI135803/AI/NIAID NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/blood/immunology ; Machine Learning ; Metabolomics ; Multiomics ; *SARS-CoV-2/metabolism ; },
abstract = {BACKGROUNDFollowing SARS-CoV-2 infection, approximately 10%-35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.METHODSWe utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics "recovery factor," trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor scores were tested for association with LC, disease severity, clinical parameters, and immune subset frequencies. Enrichment analyses identified biologic pathways associated with recovery factor scores.RESULTSParticipants with LC had lower recovery factor scores compared with recovered participants. Recovery factor scores predicted LC as early as hospital admission, irrespective of acute COVID-19 severity. Biologic characterization revealed increased inflammatory mediators, elevated signatures of heme metabolism, and decreased androgenic steroids as predictive and ongoing biomarkers of LC. Lower recovery factor scores were associated with reduced lymphocyte and increased myeloid cell frequencies. The observed signatures are consistent with persistent inflammation driving anemia and stress erythropoiesis as major biologic underpinnings of LC.CONCLUSIONThe multiomics recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH (3U01AI167892-03S2, 3U01AI167892-01S2, 5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI057229-18, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07S1, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-1, 3U19AI1289130, U19AI128913-04S1, R01AI122220); NIH (UM1TR004528); and National Science Foundation (NSF) (DMS2310836).},
}
@article {pmid40924424,
year = {2025},
author = {Lin, JC and McCarthy, M and Potluri, S and Nguyen, D and Yan, R and Aysola, J},
title = {Long COVID and Food Insecurity in US Adults, 2022-2023.},
journal = {JAMA network open},
volume = {8},
number = {9},
pages = {e2530730},
pmid = {40924424},
issn = {2574-3805},
mesh = {Humans ; *Food Insecurity ; *COVID-19/epidemiology/complications ; Female ; Male ; Adult ; Cross-Sectional Studies ; Middle Aged ; United States/epidemiology ; Food Assistance/statistics &amp; numerical data ; Retrospective Studies ; SARS-CoV-2 ; Aged ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Young Adult ; *Food Supply/statistics &amp; numerical data ; },
abstract = {IMPORTANCE: Long COVID (ie, post-COVID-19 condition) is a substantial public health concern, and its association with health-related social needs, such as food insecurity, remains poorly understood. Identifying modifiable risk factors like food insecurity and interventions like food assistance programs is critical for reducing the health burden of long COVID.<br><br>OBJECTIVE: To investigate the association of food insecurity with long COVID and to assess the modifying factors of Supplemental Nutrition Assistance Program (SNAP) participation and employment status.<br><br>This retrospective, cross-sectional survey study used data from the 2022 to 2023 National Health Interview Survey. Respondents aged 18 years and older who reported prior COVID-19 infection and responded to questions on food insecurity and long COVID were included.<br><br>EXPOSURE: Food insecurity, categorized as food secure or food insecure.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was current long COVID, defined as symptoms lasting 3 or more months after initial COVID-19 infection persisting to time of interview. The secondary outcome was long COVID recovery, indicating history of long COVID without current symptoms. Food insecurity was measured using the validated 10-item National Center for Health Statistics food insecurity scale. Odds ratios (ORs) and 95% CIs for the association of food insecurity with long COVID were calculated using simple and multiple logistic regression.<br><br>RESULTS: The study enrolled 21&#x202f;631 participants (1255 female [weighted percentage, 53%]; 5058 aged 65 years or older [weighted percentage, 16%]), including 19&#x202f;824 with food security and 1807 with food insecurity. In total, 288 respondents with food insecurity (weighted percentage, 15%) reported current long COVID compared with 1547 (weighted percentage, 7%) without food insecurity. Food insecurity was positively associated with current long COVID (adjusted OR, 1.73; 95% CI, 1.39-2.15) and negatively associated with recovery among adults with prior long COVID (adjusted OR, 0.70; 95% CI, 0.54-0.92). SNAP participation (P for interaction&#x2009;=&#x2009;.04) and unemployment (P for interaction&#x2009;=&#x2009;.04) significantly modified these associations.<br><br>CONCLUSIONS AND RELEVANCE: In this survey study of US adults with prior COVID-19 infection, food insecurity was associated with greater odds of long COVID and lower odds of recovery, with SNAP participation and unemployment mitigating these associations. These findings suggest that expanding SNAP eligibility, simplifying enrollment processes, and increasing awareness of food assistance programs may reduce the burden of food insecurity and long COVID and further emphasize the importance of addressing health-related social needs in chronic disease prevention and management.},
}
@article {pmid40922860,
year = {2025},
author = {Potluri, S and Chittiprol, N and Varaganti, V and Avr, V and Vadakedath, S and Arvapally, D and Vemulapalli, C and Begum, GS and Madamsetti, N and Kandi, V},
title = {The Association of SARS-CoV-2 Infection and COVID-19 Vaccination With Sudden Death: An Explorative Review.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89527},
pmid = {40922860},
issn = {2168-8184},
abstract = {Since its discovery, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become the epicenter of public health concern. This was mainly attributed to the complexity of COVID-19 that resulted in variable disease progression with some developing asymptomatic infections, some suffering mild to moderate infections that resolved without the need for hospitalizations, and a few infected persons developing severe infections that required intensive care unit (ICU) admission and mechanical ventilation. The COVID-19 pandemic spread globally, affecting billions of people and killing millions. Most of the consequences were related to the novelty of the virus, poor understanding of its pathogenesis, and the lack of a specific antiviral drug and vaccine. The vaccines, although manufactured and made available to the public, were approved for emergency use before the completion of human clinical trials. Moreover, the continuous emergence of viruses following mutations resulted in the emergence of viral variants. This has led to doubts over the efficacy of vaccines. Vaccine inequity, represented by the disproportionate availability and distribution of vaccines among the rich and poor, concerns over long-term safety, and hesitancy, affected COVID-19 vaccination, thereby increasing the spread of SARS-CoV-2. Although the COVID-19 pandemic is no longer considered a public health emergency of international concern (PHEIC), the repercussions of the pandemic are still evident in the form of long COVID and post-COVID functional health status (PCFHS), wherein individuals who were previously infected continue to suffer organ dysfunction, primarily affecting the lungs and other organs of the body. During and after the pandemic, COVID-19 and probably vaccination were attributed to the death of many individuals, which were categorized as sudden death (SD) and sudden unnatural death (SUD). It is unclear if these deaths were a result of previous SARS-CoV-2 infection and prior COVID-19 vaccination or both. There are several instances of infected and recovered individuals who were healthy but suddenly developed complications and died. Through this explorative review, we aim to comprehend the role that SARS-CoV-2 infection and/or COVID-19 vaccination play in predisposing people to cardiovascular system (CVS) and central nervous system (CNS) disorders that can result in SD and SUD.},
}
@article {pmid40922488,
year = {2025},
author = {White, RA and Nygaard, AB and Søraas, A and Nyborg, GA},
title = {Excess all-cause mortality in Norway in 2024.},
journal = {Scandinavian journal of public health},
volume = {},
number = {},
pages = {14034948251371830},
doi = {10.1177/14034948251371830},
pmid = {40922488},
issn = {1651-1905},
abstract = {AIMS: The Norwegian Institute of Public Health calculated excess mortality for Norway in 2024 using a reference period that included 2023-a year with significant excess mortality-and concluded there was no excess mortality in 2024. This study estimates excess mortality in 2024 using only pre-pandemic years as the reference, providing a basis for identifying excess COVID-19 related mortality.<br><br>METHODS: We estimated excess mortality in 2024 using a negative binomial model trained on 2010-2019 data. Deaths were modelled by age (0, 1-19, 20-39, 40-64, 65-79, 80-89 and 90+ years) and sex, with population offsets. Expected mortality was projected using both a conservative approach where the prediction for 2023 was carried forward to 2024 and a non-conservative linear extrapolation to 2024.<br><br>RESULTS: The conservative approach estimated 2898 excess deaths (7.0%; 95% prediction interval (PI), 4.9-9.1%) in 2024. Significant excess mortality was observed in age groups 1-19 (45 deaths; 36.6% excess), 20-39 (107 deaths; 17.6% excess), 40-64 (439 deaths; 10.6% excess) and 65-79 (1631 deaths; 13.7% excess). Ages 1-39 and 40-64 accounted for approximately 5% and 15% of total excess mortality, respectively.<br><br>CONCLUSIONS: Persistent excess mortality from 2022 to 2024 suggests a new elevated mortality baseline and a reduction or reversal of Norway's pre-pandemic mortality decline. Although multiple factors may contribute, given sustained excess mortality since 2022, our findings suggest that the unmitigated spread of SARS-CoV-2 in Norway since 2022 can be associated with increased mortality, particularly for those under 65.},
}
@article {pmid40922273,
year = {2025},
author = {Pires, L and Marreiros, A and Saraiva, C and Reis, C and Neves, D and Guerreiro, C and Tomé, JB and Luz, MI and Pereira, MI and Barroso, AS and Ferreira, J and Gonzalez, LM and Moniri, A and Drummond, M and Berger-Estilita, J},
title = {Association of acute COVID-19 severity and long COVID fatigue and quality of life: Prospective cohort multicenter observational study.},
journal = {Medicine},
volume = {104},
number = {36},
pages = {e42891},
pmid = {40922273},
issn = {1536-5964},
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/complications/psychology/epidemiology ; Male ; Female ; *Fatigue/etiology/epidemiology/psychology ; Prospective Studies ; Middle Aged ; Severity of Illness Index ; Anxiety/epidemiology/etiology ; Adult ; Depression/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; Portugal/epidemiology ; },
abstract = {Long COVID, or post-COVID-19 condition, is characterized by symptoms persisting beyond 12 weeks after severe acute respiratory syndrome coronavirus 2 infection, affecting individuals regardless of acute disease severity. Fatigue - often linked with depression and anxiety - is among its most debilitating manifestations. However, the associations between fatigue subtypes (physical vs mental), mental health symptoms, and acute disease severity on long-term health-related quality of life (HRQoL) remain unclear. This study examines the relationships between long COVID fatigue, depression, anxiety, acute disease severity, and HRQoL in a post-COVID-19 cohort. This prospective observational cohort study was conducted across 5 Portuguese hospitals between November 2020 and June 2022. Adults (≥18 years) with confirmed severe acute respiratory syndrome coronavirus 2 infection ≥6 months prior and fulfilling World Health Organization criteria for long COVID were included. Acute Coronavirus disease 2019 (COVID-19) severity was classified per World Health Organization definitions. The sampling strategy included patients across the severity spectrum. At 3 months postinfection (T1), patients received physician-led clinical assessments. At 6 months (T2), they attended in-person follow-up visits, completing standardized forms and validated questionnaires assessing post-acute sequelae. Fatigue was reported both binarily (yes/no) and via the chalder fatigue scale (11-item version). Anxiety and depression were assessed using the hospital anxiety and depression scale; post-traumatic stress disorder symptoms with the 14-item post-traumatic stress scale; and HRQoL with the EuroQol-5 dimensions. Descriptive statistics, analysis of variance, chi-square, and correlation analyses (Pearson's or Spearman's) were used to evaluate associations. Analyses were performed using SPSS (v27; IBM Corp., Amonk). Among 208 patients, fatigue was significantly associated with anxiety and depression (P < .001). Physical fatigue correlated more strongly with depression (r = 0.65, P < .001) and anxiety (r = 0.58, P < .001) than mental fatigue (r = 0.50 and R = 0.48, respectively; P < .001). Surprisingly, severe acute COVID-19 cases reported lower fatigue (CFQ: 13.3 ± 8.4) than mild (17.7 ± 7.2) or moderate (17.4 ± 8.0) cases (P < .005), and higher HRQoL (EuroQol visual analog scale: 74.3 ± 20.3, P = .002). Anxiety symptoms were more common in mild cases (P < .001); post-traumatic stress disorder symptoms did not differ by severity. Long COVID fatigue - especially physical - is strongly linked to depression and anxiety. Mild/moderate acute COVID-19 cases show greater fatigue and lower HRQoL than severe cases, highlighting the need for tailored long-term care regardless of initial severity.},
}
@article {pmid40921327,
year = {2025},
author = {Dias Claudio, F and Vallejo, N and Mateu, L and Bayes-Genis, A and Delgado, V and Teis, A},
title = {Chest pain in long COVID disease. Insights from stress cardiovascular magnetic resonance.},
journal = {Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology},
volume = {44},
number = {10},
pages = {649-651},
doi = {10.1016/j.repc.2025.03.008},
pmid = {40921327},
issn = {2174-2030},
}
@article {pmid40920586,
year = {2026},
author = {Orlinick, B and Mehta, S and McAlpine, L and Khoshbakht, S and Fertuzinhos, S and Nelson, A and Chiarella, J and Das, B and Patel, V and Filippidis, P and Corley, MJ and Spudich, SS and Farhadian, SF},
title = {Cerebrospinal Fluid Immune Cell Alterations in Women With Neuropsychiatric Long COVID.},
journal = {The Journal of infectious diseases},
volume = {233},
number = {1},
pages = {e109-e117},
pmid = {40920586},
issn = {1537-6613},
support = {L30 NS139301/NS/NINDS NIH HHS/United States ; 1S10OD030363-01A1./GF/NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; R01AI157488/GF/NIH HHS/United States ; R01 MH125737/MH/NIMH NIH HHS/United States ; R01MH125737-S/GF/NIH HHS/United States ; S10 OD030363/OD/NIH HHS/United States ; },
mesh = {Humans ; Female ; *COVID-19/cerebrospinal fluid/immunology/complications/psychology ; Middle Aged ; Leukocytes, Mononuclear/immunology ; Adult ; SARS-CoV-2 ; Aged ; *Cerebrospinal Fluid/cytology/immunology ; },
abstract = {BACKGROUND: Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19. However, whether there are central nervous system-specific changes in gene expression in women with neuropsychiatric Long COVID (NP-Long COVID) remains unknown.<br><br>METHODS: Twenty-two women with and 10 women without NP-Long COVID were enrolled from New Haven, Connecticut, and the surrounding region and consented to a blood draw and large volume lumbar puncture. Total RNA was extracted from cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMC). Polyadenylated RNA was sequenced, and differential expression analyses were performed.<br><br>RESULTS: Both CSF and PBMC samples showed differential gene expression associated with Long COVID status. There were CSF-specific differentially expressed genes in people with Long COVID, including in genes related to oxidative stress, reactive oxygen species, and P53 response, indicating compartment-specific immune responses. Some pathways were dysregulated in both the CSF and PBMC of Long COVID compared with controls, including those related to androgen response, MTORC1 signaling, and lipid metabolism.<br><br>CONCLUSIONS: Women with NP-long COVID show compartment-specific, transcriptional profiles in the CSF with evidence of enrichment in cellular stress pathways. These results underscore the importance of examining CSF-specific molecular profiles to better understand post-viral neurological syndromes.},
}
@article {pmid40918941,
year = {2025},
author = {Bunnell, HT and Reedy, C and Lorman, V and Jhaveri, R and Rivera-Sepulveda, A and Salamon, KS and Patel, PB and Morse, KE and Davenport, MA and Cowell, LG and Utidjian, L and Christakis, DA and Rao, S and Sills, MR and Case, A and Mendonca, EA and Taylor, BW and Rutter, J and Martinez, AT and Letts, R and Bailey, LC and Forrest, CB and , },
title = {A natural language processing pipeline for identifying pediatric long COVID symptoms and functional impacts in freeform clinical notes: a RECOVER study.},
journal = {JAMIA open},
volume = {8},
number = {5},
pages = {ooaf089},
pmid = {40918941},
issn = {2574-2531},
abstract = {OBJECTIVE: To develop a natural language processing (NLP) pipeline for unstructured electronic health record (EHR) data to identify symptoms and functional impacts associated with Long COVID in children.<br><br>MATERIALS AND METHODS: We analyzed 48&#xa0;287 outpatient progress notes from 10&#xa0;618 pediatric patients from 12 institutions. We evaluated notes obtained 28 to 179 days after a COVID-19 diagnosis or positive test. Two samples were examined: patients with evidence of Long COVID and patients with acute COVID but no evidence of Long COVID based on diagnostic codes. The pipeline identified clinical concepts associated with 21 symptoms and 4 functional impact categories. Subject matter experts (SMEs) screened a sample of 4586 terms from the NLP output to assess pipeline accuracy. Prevalence and concordance of each of the 25 concepts was compared between the 2 patient samples.<br><br>RESULTS: A binary assertion measure comparing SME and NLP assertions showed moderate accuracy (N&#x2009;=&#x2009;4133; F1 = .80) and improved substantially when only high-confidence SME assertions were considered (N&#x2009;=&#x2009;2043; F1 = .90). Overall, the 25 Long COVID concept categories were markedly more prevalent in the presumptive Long COVID cohort, and differences were noted between concepts identified in notes versus structured data.<br><br>DISCUSSION: This preliminary analysis illustrates the additional insight into a syndrome such as Long COVID gained from incorporating notes data, characterizing symptoms and functional impacts.<br><br>CONCLUSION: These data support the importance of incorporating NLP methodology when possible into designing computable phenotypes and to accurately characterize patients with Long COVID.},
}
@article {pmid40918680,
year = {2025},
author = {Sadat Larijani, M and Bavand, A and Ashrafian, F and Moradi, L and Ramezani, A},
title = {Late-Induced Autoimmune Disorders Post-COVID-19 Vaccination/Infection: Case Report From Iran.},
journal = {Case reports in medicine},
volume = {2025},
number = {},
pages = {8815875},
pmid = {40918680},
issn = {1687-9627},
abstract = {COVID-19 pandemic led to a fast vaccine design due to the threat of rapid spreading worldwide. Safety profile of the approved vaccines has been achieved mostly through clinical trials. However, some unsolicited adverse events in a longer duration of time have been recorded in addition to the late disorders known as long-COVID, stemming from classical infection. Therefore, case studies and long-term follow-up are required to enrich the current data on SARS-COV-2 infection/vaccination. In this study, two cases of autoimmune diseases induced by COVID-19 and/or vaccination were followed in three years. The profile of each is presented, and the probable cause has been discussed. The laboratory findings approved systematic lupus erythematosus and Hashimoto's thyroiditis in the studied cases. The key finding of this study is that the importance of probable autoimmune diseases flares up in individuals with a history of autoimmunity in their families which could manifest as a long-COVID symptom or late vaccination side effect.},
}
@article {pmid40917843,
year = {2025},
author = {Gu, L and Yue, J and Lin, J and Liu, Z and Huang, JA},
title = {Challenges in diagnosis and treatment of long COVID.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1641411},
pmid = {40917843},
issn = {2296-858X},
abstract = {Despite a large population affected by COVID-19, awareness of long COVID among clinicians is surprisingly limited. This has led to delayed or missed diagnoses and, consequently, inappropriate treatments that fail to address patients' specific needs. Our study highlights the gaps in knowledge and the barriers to effective management of long COVID in the healthcare system. Through this work, we aim to bring attention to these critical issues and advocate for urgent action to improve the clinical management of long COVID.},
}
@article {pmid40914478,
year = {2025},
author = {Houweling, L and Holtjer, JCS and Bloemsma, LD and de Jong, PA and Mohamed Hoesein, FA and Nossent, EJ and Vermeulen, RCH and Maitland-Van der Zee, AH and Downward, GS},
title = {Air pollution and long COVID: association with pulmonary function and radiological abnormalities 3-15 months post-COVID.},
journal = {Environmental research},
volume = {286},
number = {Pt 1},
pages = {122707},
doi = {10.1016/j.envres.2025.122707},
pmid = {40914478},
issn = {1096-0953},
mesh = {Humans ; *COVID-19/physiopathology/diagnostic imaging/epidemiology ; Male ; Female ; *Air Pollution/adverse effects/analysis ; Middle Aged ; *Lung/diagnostic imaging/physiopathology ; Aged ; Adult ; Particulate Matter/analysis ; Respiratory Function Tests ; *Air Pollutants/analysis/adverse effects ; *Environmental Exposure ; Tomography, X-Ray Computed ; SARS-CoV-2 ; },
abstract = {While studies have examined associations between air pollution and subjective long COVID outcomes such as fatigue and symptoms, no studies have focused on objective lung health measures. This study aimed to assess the impact of air pollution, examined through different exposure methods (exposures assigned via geospatial model, versus residential and personal measurements) on pulmonary function and radiological abnormalities in long COVID patients. We recruited 95 patients who attended a hospital outpatient clinic 3-6 months post-infection, during which pulmonary function was assessed via spirometry (FEV1,FVC,FEV1/FVC ratio) and diffusion capacity for carbon monoxide (DLCO), along with a chest CT. Of these, 38 patients with abnormalities in one of the assessed modalities returned for a follow-up visit approximately nine months later. Ambient levels of PM2.5, PM10, NO2, and O3 was assigned using land-use regression models, while residential and personal PM2.5 measurements were collected between the hospital visits in the participants' home environments. No associations were found between residential (assigned or measured) air pollution exposure and pulmonary function or radiological abnormalities at the first visit. Pulmonary function also typically improved between the first and second visit. However, an association between personal exposure and CT abnormalities was observed. A one IQR(12.3 μg/m[3]) increase in personal PM2.5 significantly increased the risk of airway abnormalities during the follow-up visit (adjusted OR:3.35, 95 %CI:1.03,14.63), particularly mosaic patterns (OR:5.74, 95 %CI:1.43,40.62). These findings add to evidence of exposure to air pollution playing a role in long COVID and call for mitigation measures to improve air quality.},
}
@article {pmid40914131,
year = {2025},
author = {Dixon, BE and Allen, KS and Simmons, N and Brinkley, J and Andrews, JG and Dzomba, BJ and Feiler, MO and Jones, RM and Ortiz, MR and Sharma, V and Dalton, AF and Pratt, C and Grannis, SJ and Saydah, SH and , },
title = {Incidence of long COVID among U.S. children and adults during the omicron era - Tracking Post-COVID Conditions (Track-PCC) network, 2022-2023.},
journal = {Journal of infection and public health},
volume = {18},
number = {11},
pages = {102935},
doi = {10.1016/j.jiph.2025.102935},
pmid = {40914131},
issn = {1876-035X},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Incidence ; Child ; United States/epidemiology ; Adult ; Male ; Female ; Adolescent ; Middle Aged ; Child, Preschool ; Young Adult ; Aged ; SARS-CoV-2 ; Infant ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; },
abstract = {BACKGROUND: Long COVID, or Post-COVID Conditions (PCC), refers to new and persisting sequelae occurring in the months following an acute SARS-CoV-2 infection. Although previous studies have reported estimates of PCC incidence, few have examined trends during the Omicron variant period or have included geographically distinct regions for the same time periods.<br><br>METHODS: Track PCC is a surveillance network, leveraging electronic health records and public health data to monitor incidence over time across five diverse geographic sites in the U.S. This study examines the incidence of PCC in children and adults during the Omicron predominance period (January 1, 2022, to December 31, 2023) through April 2024. Incident conditions were identified using diagnostic codes for 49 conditions. Crude and adjusted incidence for the occurrence of PCC per 1000 person-days was calculated independently during three post-acute time periods: 31-90 days, 91-180 days, and 181-365 days. Incidence of PCC per 1000 person-days was also calculated by demographic and clinical characteristics.<br><br>RESULTS: The Track PCC network included 438,491 adults and 85,264 children with COVID-19 during the Omicron period. PCC incidence was highest 31-90 days post-acute; range from 2.95 to 5.05 per 1000 person-days among adults and 1.53-3.15 per 1000 person-days among children. Incidence was higher among older patients and patients with 3 or more co-morbidities and generally stable across variant sublineage periods.<br><br>CONCLUSION: These data suggest the PCC incidence following acute COVID-19 has not increased during the Omicron period. This is useful for understanding the burden of PCC and estimating demand of medical services following acute COVID-19 infections. PCC surveillance, including tracking the incidence of PCC, understanding patients at higher likelihood of developing PCC, and creating robust estimates, is critical to public health efforts to understand disease burden and guide prevention and treatment efforts.},
}
@article {pmid40910585,
year = {2025},
author = {Hu, C and Son, J and McAlpine, L and Walker, ELS and Dahl, M and Song, E and Ferreira Brito, S and Kavak, K and Onomichi, K and Bar-Or, A and Perrone, C and Riley, CS and Weinstock-Guttman, B and De Jager, PL and Longbrake, EE and Xia, Z},
title = {Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study.},
journal = {Annals of clinical and translational neurology},
volume = {12},
number = {12},
pages = {2446-2459},
pmid = {40910585},
issn = {2328-9503},
support = {L30 NS139301/NS/NINDS NIH HHS/United States ; R01NS124882//National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; R01NS098023//National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {Humans ; Female ; Cross-Sectional Studies ; *COVID-19/epidemiology/complications/physiopathology ; Middle Aged ; *Multiple Sclerosis/epidemiology/complications/physiopathology ; Male ; Adult ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Managing long COVID in people with multiple sclerosis and related disorders (pwMSRD) is complex due to overlapping symptoms. To address evidence gaps, we evaluated long COVID susceptibility in pwMSRD versus controls and its associations with multi-domain function and disability.<br><br>METHODS: In this multicenter cross-sectional study, participants completed a survey covering 71 post-infection symptoms, distinguishing new-onset from worsening symptoms. We defined long COVID using the 2024 NASEM criteria. Logistic regression assessed long COVID odds. Linear and Poisson regression evaluated associations with function and disability.<br><br>RESULTS: 969 pwMSRD (82.5% female, mean age 51.8&#x2009;years, 63.5% infected) and 1003 controls (79.4% female, mean age 45.2&#x2009;years, 61.2% infected) were included. PwMSRD had higher odds of long COVID (aOR&#x2009;=&#x2009;1.6 [1.2-2.1]), with a stronger association when restricting to worsening symptoms (aOR&#x2009;=&#x2009;2.3 [1.7-3.1]). Having long COVID was associated with worse physical function, cognition, and depression in both groups. PwMSRD with long COVID experienced greater physical function declines and more depression severity exacerbation than controls, and had faster disability progression compared to those without long COVID.<br><br>CONCLUSION: PwMSRD show&#xa0;increased susceptibility to long COVID, primarily driven by worsening symptoms. Long COVID contributes to more functional decline and disability worsening. Recognizing and managing long COVID is essential for pwMSRD.},
}
@article {pmid40910058,
year = {2025},
author = {Mazzali, C and Magnoni, P and Zucchi, A and Maifredi, G and Cavalieri d'Oro, L and Gambino, ML and Fanetti, AC and Perotti, PG and Villa, M and Valsecchi, MG and Vigani, D and Lucifora, C and Russo, AG},
title = {Strategies for population-level identification of post-acute sequelae of COVID-19 through health administrative data.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1637112},
pmid = {40910058},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 (PASC) encompass several clinical outcomes, from new-onset symptoms to both acute and chronic diagnoses, including pulmonary and extrapulmonary manifestations. Health administrative data (HAD) from health information systems allow population-level analyses of such outcomes. Our primary aim was to identify clinical conditions potentially attributable to SARS-CoV-2 infection, and the types of HAD and "diagnostic criteria" used for their detection.<br><br>METHODS: We performed a literature review to identify HAD-based cohort studies assessing the association between SARS-CoV-2 infection and medium-/long-term outcomes in the general population. From each included study, we extracted data on design, algorithms used for outcome identification (sources, coding systems, codes, time criteria/thresholds), and whether significant associations with SARS-CoV-2 infection were reported.<br><br>RESULTS: We identified six studies investigating acute and chronic conditions grouped by clinical domain (cardiovascular, respiratory, neurologic, mental health, endocrine/metabolic, pediatric, miscellaneous). Two studies also addressed the onset of specific symptoms. Cardio/cerebrovascular conditions were most studied, with significant associations reported for deep vein thrombosis, heart failure, atrial fibrillation, and coronary artery disease. Conditions in other domains were less investigated, with inconsistent findings. Only three studies were designed as test-positive vs. test-negative comparisons.<br><br>DISCUSSION: Heterogeneity in data sources, study design, and outcome definitions hinder the comparability of studies and explain the inconsistencies in findings about associations with SARS-CoV-2 infection. Rigorously designed studies on large populations with wide availability of data from health information systems are needed for population-level analyses on PASC, and especially on its impact on chronic diseases and their future burden on healthcare systems.},
}
@article {pmid40909985,
year = {2025},
author = {Salker, P},
title = {My Long COVID Journey - How To Slay Dragons Using Neuroplasticity.},
journal = {Journal of lifestyle medicine},
volume = {15},
number = {2},
pages = {87-89},
pmid = {40909985},
issn = {2234-8549},
abstract = {Framed through the long COVID experience of a United Kingdom physician, this narrative delineates the neurobiological consequences of chronic stress and highlights the role of neuroplastic interventions in facilitating physiological and cognitive recovery.},
}
@article {pmid40909835,
year = {2025},
author = {Chen, Z and Li, B and Chen, Y and Liu, J and Luo, F and Ogunyemi, KO and Ge, Y and Ke, Y and Yang, Y and Chen, X and Shen, Y},
title = {Mapping Long COVID: Spatial and Social Inequities Across the United States.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40909835},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; 75N90023D00001/CL/CLC NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; 75N99023D00001/OF/ORFDO NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; 75N95021D00001/DA/NIDA NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; 75N94023D00001/HD/NICHD NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; 75N92023D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Long COVID affects a substantial portion of the U.S. population, yet its spatiotemporal distribution remains poorly characterized. The emergence of the Omicron variant and persistent sociodemographic disparities may contribute to regional variation in long COVID risk. Understanding the patterns of long COVID is essential to implementing targeted and equitable public health interventions.<br><br>METHODS: This retrospective study utilized data from the National COVID Cohort Collaborative (N3C), covering 5,652,474 COVID-19 cases and 41,694 long COVID cases across 1,063 U.S. counties from 2021 to 2024. Temporal patterns of long COVID were analyzed before and after the Omicron variant's emergence, and spatial patterns were assessed using Moran's I and Getis statistics. Bayesian spatial random effect models were employed to evaluate the associations between long COVID incidence and sociodemographic factors such as economic vulnerability, healthcare access, and mobility.<br><br>FINDINGS: Quarterly long COVID incidence ranged from 0.015% to 14.29%. Before the emergence of the Omicron variant, incidence was 204 cases per 10,000 COVID-19 cases, compared with 248 cases per 10,000 COVID-19 cases after Omicron emergence (p < 0.001). After Omicron's emergence, 48.8% [328 of 673] of counties showed significant spatial correlation (p < 0.05), up from 43.5% [293 of 673] prior. High-risk areas became more concentrated in inland regions, while low-risk areas clustered along the East Coast. Long COVID incidence was significantly associated with economic vulnerability, limited healthcare access, and mobility constraints, with these sociodemographic disparities consistently driving its spatial disparities over time.<br><br>INTERPRETATION: These findings underscore the need to address spatial and social inequities in long COVID risk. Targeted public health interventions, particularly in economically and geographically vulnerable regions, are essential to ensure equitable access to diagnosis, care, and resource allocation.<br><br>FUNDING: Y. Shen received partial support from NIH grants/contracts R35GM146612, R01AI170116, and 75N93019C00052.},
}
@article {pmid40909786,
year = {2025},
author = {Wei, WQ and Guardo, C and Zhang, X and Gandireddy, S and Yan, C and Kerchberger, V and Dickson, A and Pfaff, E and Master, H and Basford, M and Chute, C and Tran, N and Manusco, S and Syed, T and Zhao, Z and Feng, Q and Haendel, M and Lunt, C and Harris, P and Li, L and Ginsburg, G and Denny, J and Roden, D},
title = {Multi-scale Data Improves Performance of Machine Learning Model for Long COVID Prediction.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40909786},
issn = {2693-5015},
support = {U2C OD023196/OD/NIH HHS/United States ; OT2 OD025315/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; OT2 OD026549/OD/NIH HHS/United States ; OT2 OD025337/OD/NIH HHS/United States ; OT2 OD025277/OD/NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; OT2 OD023205/OD/NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; OT2 OD026556/OD/NIH HHS/United States ; R01 AG069900/AG/NIA NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; R01 GM139891/GM/NIGMS NIH HHS/United States ; K01 HL157755/HL/NHLBI NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; U01 HG011181/HG/NHGRI NIH HHS/United States ; },
abstract = {Long COVID affects a substantial proportion of the over 778 million individuals infected with SARS-CoV-2, yet predictive models remain limited in scope. While existing efforts, such as the National COVID Cohort Collaborative (N3C), have leveraged electronic health record (EHR) data for risk prediction, accumulating evidence points to additional contributions from social, behavioral, and genetic factors. Using a diverse cohort of SARS-CoV-2-infected individuals (n>17,200) from the NIH All of Us Research Program, we investigated whether integrating EHR data with survey-based and genomic information improves model performance. Our multi-scale approach outperformed EHR-only models original AUROC 0.736 (95% CI: 0.730, 0.741), achieving an AUROC of 0.748 (0.741,0.755). Among the top predictors, active-duty service status, self-reported fatigue, and chr19:4719431:G:A_A were among the most informative survey and genetic features. These findings highlight the importance of incorporating multi-scale data to improve risk stratification and inform personalized interventions for long COVID.},
}
@article {pmid40908845,
year = {2025},
author = {Leighton, J and Nelson, MLA and Sheppard, CL and Wasilewski, M and Reis, L and Vijayakumar, A and Hitzig, SL and Robinson, LL and Levy, C and Ho, C and Steinberg, R and Goulding, S and Simpson, R},
title = {'You're alive, but are you living?' Exploring long COVID (LC)'s impact on social and leisure well-being for individuals and caregivers.},
journal = {Psychology &amp; health},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/08870446.2025.2552233},
pmid = {40908845},
issn = {1476-8321},
abstract = {Long COVID (LC) affects physical health and cognition, limiting participation in social and leisure activities. As a novel disabling condition following a COVID-19 infection, informal caregivers of those with LC have taken on expanded roles, including educating themselves on this diagnosis. Gathering insights from people living with LC (PWLC) and their caregivers is crucial for understanding its impact on well-being and identifying targeted rehabilitation practices across the LC care pathway. Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with LC and 15 caregivers). Results: Composite narratives were created to introduce three key themes: (1) The demands of managing physical and cognitive symptoms of LC limit the ability of PWLC and caregivers to engage in social and leisure activities; (2) The loss of meaningful social and leisure activities deepens a diminished sense of identity for PWLC and caregivers; and (3) The absence of shared social and leisure engagement intensifies feelings of disconnection and loneliness for PWLC and caregivers. The findings support a need for more social- and leisure-targeted interventions for LC rehabilitation to help to optimize efforts for coping with the psychosocial impacts of living with, or caring for someone with, LC.},
}
@article {pmid40908304,
year = {2025},
author = {Ivković, V and Anandh, U and Bell, S and Kronbichler, A and Soler, MJ and Bruchfeld, A},
title = {Long COVID and the kidney.},
journal = {Nature reviews. Nephrology},
volume = {21},
number = {12},
pages = {833-845},
pmid = {40908304},
issn = {1759-507X},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Renal Insufficiency, Chronic/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; },
abstract = {Long coronavirus disease (COVID) - commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis - is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.},
}
@article {pmid40908194,
year = {2026},
author = {Colombo, C and Medino, P and Cipolli, M and Lucca, F and Cucchetto, G and Alghisi, F and Ciciriello, F and Sepe, A and Romano, C and Taccetti, G and Francalanci, M and Ambroni, M and Donati, V and Pizzamiglio, G and Spotti, M and Rotolo, N and Lucanto, MC and Cristadoro, S and Ficili, F and Leonetti, G and Giordano, P and Bignamini, E and Rizza, E and Pisi, G and Fainardi, V and Casciaro, R and Formigoni, C and Ros, M and Comello, I and Poli, P and Vitullo, P and Messore, B and Riberi, L and Palladino, N and Rosazza, C and Alicandro, G and Blasi, F},
title = {COVID-19 in people with Cystic Fibrosis beyond the pre-omicron era: a prospective study with a specific focus on long COVID.},
journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society},
volume = {25},
number = {1},
pages = {172-178},
doi = {10.1016/j.jcf.2025.08.015},
pmid = {40908194},
issn = {1873-5010},
mesh = {Humans ; *Cystic Fibrosis/epidemiology/complications/physiopathology ; *COVID-19/epidemiology/diagnosis/physiopathology/therapy/complications ; Male ; Female ; Prospective Studies ; Adolescent ; Adult ; SARS-CoV-2 ; Child ; Incidence ; Hospitalization/statistics &amp; numerical data ; Young Adult ; },
abstract = {BACKGROUND: The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF.<br><br>METHODS: This prospective, multicentre study enrolled individuals with confirmed SARS-CoV-2 infection between July 2021 and October 2022. Data collected included clinical features prior to infection, symptoms during the acute phase, hospitalization and symptom persistence after 1 and 6 months. Long COVID was defined according to CDC criteria as persistence of at least one COVID-related symptom for one or more months after diagnosis. The mean variation of FEV1 recorded 6 months after acute infection was also evaluated.<br><br>RESULTS: A total of 1102 people with CF were recruited (median age: 18 years, 520 younger than 18). The infection was symptomatic in 90.1&#x202f;% of cases. During the acute phase, 8 subjects required oxygen support; 31 were hospitalized, one patient required intensive care. Complications included one thromboembolic event and two episodes of myocarditis, but no patient died. Mean variation of FEV1 after 6 months from the infection was +1.8&#x202f;% (95&#x202f;% CI: 1.0-2.7). Long COVID was documented in 64 subjects (5.8&#x202f;%, 95&#x202f;% CI: 4.5-7.4) with a variety of symptoms which were still present in 12 cases 6 months after infection (1.1&#x202f;%, 95&#x202f;% CI: 0.6-1.9).<br><br>CONCLUSIONS: In the omicron phase of the pandemic, COVID-19 was relatively mild and did not negatively impact pulmonary function after 6 months. Long COVID was observed at all ages, but extrapulmonary symptoms were more frequent and persistent in adults.},
}
@article {pmid40907708,
year = {2025},
author = {Tashima, R and Kuroda, T and Nobori, H and Miyagawa, S and Yamane, T and Shimba, A and Nakashima, M and Fukao, K},
title = {Ensitrelvir suppresses prolonged olfactory abnormalities derived from SARS-CoV-2 infection in hamsters.},
journal = {Antiviral research},
volume = {243},
number = {},
pages = {106270},
doi = {10.1016/j.antiviral.2025.106270},
pmid = {40907708},
issn = {1872-9096},
mesh = {Animals ; Cricetinae ; *COVID-19/complications/virology ; *SARS-CoV-2/drug effects ; *COVID-19 Drug Treatment ; Disease Models, Animal ; *Olfaction Disorders/drug therapy/virology/etiology ; Male ; *Antiviral Agents/therapeutic use/pharmacology ; Mesocricetus ; Smell/drug effects ; Turbinates/pathology/drug effects/virology ; *Leucine/analogs &amp; derivatives/therapeutic use ; Indazoles ; Triazines ; Triazoles ; },
abstract = {Ensitrelvir, an oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease inhibitor, is reportedly effective in suppressing smell disorder onset, a post-coronavirus disease 2019 (COVID-19) condition symptom. However, the pathogenesis of post-COVID-19 condition symptoms and the mechanism underlying the onset-suppressive effect of ensitrelvir are not fully understood. Here, we explored a post-COVID-19 condition model in hamsters 1 month post-SARS-CoV-2 infection and showed that ensitrelvir treatment caused early recovery of body weight, viral RNA suppression, and sense of smell improvement. In the nasal turbinates, SARS-CoV-2 was associated with significantly increased inflammatory markers, many of which were suppressed by ensitrelvir. Significant positive correlations were observed between smell testing and many inflammation-related markers in the nasal turbinates. In conclusion, our study indicates that chronic inflammation may occur in the nasal turbinates over a long period post-SARS-CoV-2 infection, leading to smell disorder onset in a hamster model. Early ensitrelvir treatment post-infection suppressed inflammation in the nasal turbinates and prevented smell disorder onset.},
}
@article {pmid40906352,
year = {2025},
author = {Tobey, M and Purvis, SJ and Daubman, BR and Isaacson, MJ and Duran, T and Johnson, G and LaPlante, JR and Armstrong, K},
title = {The Experience of Long COVID Among American Indian Individuals in Three Great Plains Communities.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {40906352},
issn = {2196-8837},
support = {R01 CA240080/CA/NCI NIH HHS/United States ; },
abstract = {Long COVID may impact populations differently. In July 2023, at the direction of a community advisory board, we administered a cross-sectional survey to explore attitudes and experiences of long COVID among members of three American Indian Reservation communities in the Great Plains. Just over half of the 843 respondents considered long COVID to be an important issue in their community, an attitude that was associated with younger age, identifying as male, having more than a high school education, full-time employment, living with children, and living on the Reservation. Of survey respondents who reported having had COVID-19, 40% reported ongoing symptoms at the time of the survey. Having ongoing symptoms was associated with identifying as female, living alone with children, and having had long COVID-19 symptoms during the initial infection. To explore ongoing symptoms, we performed a factor analysis that identified three symptom clusters with distinct sociodemographic associations. The results suggest that health and workforce sequelae of COVID-19 infections may present challenges for the surveyed communities and that ongoing symptoms after COVID-19 infection were common.},
}
@article {pmid40905682,
year = {2025},
author = {Gracie, NP and Aggarwal, A and Luo, R and Spicer, M and Idrees, S and Ashley, CL and Alca, S and Ison, T and Steain, MC and Patel, K and Siddiquee, R and Low, JKK and Mackay, JP and Denes, CE and Neely, GG and Faiz, A and Turville, SG and Newsome, TP},
title = {An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.},
journal = {Journal of virology},
volume = {99},
number = {9},
pages = {e0043525},
pmid = {40905682},
issn = {1098-5514},
support = {//Sydney Institute of Infectious Diseases/ ; //Drug Discovery Institute, University of Sydney/ ; },
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism/genetics/chemistry ; *Transforming Growth Factor beta/metabolism ; *SARS-CoV-2/metabolism ; Signal Transduction ; *Oligopeptides/metabolism ; COVID-19/virology/metabolism ; Amino Acid Motifs ; Angiotensin-Converting Enzyme 2/metabolism ; Down-Regulation ; *Interferons/metabolism ; Smad3 Protein/metabolism ; Plasminogen Activator Inhibitor 1/metabolism/genetics ; Animals ; HEK293 Cells ; },
abstract = {UNLABELLED: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates canonical cell entry via ACE2 and has also been implicated as an activator of a diverse range of signaling pathways. Here, we present evidence that the RGD (Arg-Gly-Asp) motif within the receptor-binding domain (RBD) of the S1 fragment of the S protein induces TGF-β cytokine expression. RGD peptides are well characterized as ligands for a subset of integrin complexes primarily containing α5 and αV subunits. In this study, we investigate the molecular basis of TGF-β pathway activation by S protein, delivered to cells as recombinant protein, in pseudotyped virus or in virally infected cells. Activation of TGF-β signaling by the S protein requires ACE2 and leads to SMAD3-dependent expression of the pro-fibrotic marker PAI-1. Utilizing pseudotyped viruses, expression of the S protein with a mutated RGD motif abolished TGF-β signaling, as did the RGD antagonist ATN-161, implicating integrin complexes in mediating this response. We show that the S protein RGD motif suppresses IFN-β expression via TGF-β, leading to a disruption in cellular antiviral defenses, consistent with TGF-β's role in immunosuppression. These findings further support the multifunctionality of S protein and provide mechanistic insights into its activity as a virulence factor during infection.<br><br>IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an ongoing public health challenge as a cause of acute illness and post-acute sequelae of COVID-19 (PASC, or long COVID). Our study identifies the RGD integrin-binding motif in the spike (S) protein as central to the cellular response to SARS-CoV-2, leading to the expression of the pleiotropic cytokine TGF-&#x3b2; and disabling of antiviral immunity. This work further supports the S protein-to-integrin complex signaling axis as a potential therapeutic target. The RGD motif might also be a valid target for treating PASC given the increasing body of evidence implicating the presence of persistent S protein in the etiology of this disease.},
}
@article {pmid40905101,
year = {2025},
author = {Lotankar, Y and Cheshire, A and Ridge, D and Chew-Graham, C and Smyth, N and Knowles, CR and Gopal, D and Kingstone, T and Dawson, S},
title = {Intersectionality and Long Covid: Understanding the Lived Experiences of Ethnic Minority Groups in the United Kingdom.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70413},
pmid = {40905101},
issn = {1369-7625},
support = {//Y.V.L. was funded by a PhD Studentship from the University of Westminster. C.C.G. is part-funded by West Midlands Applied Research Collaboration. Original data collection was funded by the National Institute for Health Research, under the Patient Benefit programme (NIHR203106)./ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/ethnology/psychology ; United Kingdom/epidemiology ; *Minority Groups/psychology/statistics &amp; numerical data ; Middle Aged ; *Ethnicity/psychology/statistics &amp; numerical data ; Adult ; Interviews as Topic ; Socioeconomic Factors ; Aged ; Qualitative Research ; SARS-CoV-2 ; Health Services Accessibility ; Sex Factors ; Post-Acute COVID-19 Syndrome ; Comorbidity ; },
abstract = {INTRODUCTION: Long Covid is the patient-preferred term to describe persistent symptoms experienced following an acute Covid-19 infection. The severity and unpredictable nature of long Covid symptoms can affect every aspect of an individual's life. Under-represented groups such as ethnic minorities and lower socio-economic groups are disproportionately affected by long Covid and often face challenges in accessing healthcare and additional support. This study employed an intracategorical intersectionality approach to explore how the diverse experiences of long Covid among people from ethnic minority backgrounds are influenced by complexities like gender and socio-economic factors.<br><br>METHODS: A secondary analysis of 31 semi-structured interviews with individuals with long Covid from ethnic minority backgrounds, using reflexive thematic analysis.<br><br>RESULTS: Findings are presented around the themes: (i) gender and ethnicity; (ii) socio-economic factors and illness experience; and (iii) comorbidities, disabilities and living with long Covid. Participants describe challenges in gaining support, including from health professionals, family and communities, but these challenges were gendered to a degree, with women and men describing distinctive difficulties. Financial capacity was considered important in determining the type and extent of accessible care. Support from employers also influenced participant's ability to take adequate time to recover and return to work. The interplay of comorbidities with long Covid could heighten the risk of more severe symptoms and complicate help-seeking for -and&#xa0;management of -long Covid.<br><br>CONCLUSION: An intracategorical intersectional exploration of lived experience is necessary to reveal the nuances in individual experiences of long Covid. Findings will be of interest to health professionals and researchers in supporting their understanding of intersectional experiences of their patients.<br><br>PATIENT PUBLIC INVOLVEMENT: The HI-COVE study was informed throughout by patient and expert advisory groups composed of individuals from ethnic minority backgrounds living with long Covid, their carers and professionals interested in this topic.},
}
@article {pmid40904575,
year = {2025},
author = {Shen, S and Zhao, X and Pei, J and Wang, B and Hou, J and Chai, R and Guo, Y and Li, F and Hao, J and Wu, Z},
title = {Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1555370},
pmid = {40904575},
issn = {1664-0640},
abstract = {Long COVID (LC) refers to a multisystem condition that persists after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). In addition to physical symptoms, the psychological impact is particularly pronounced. This review summarizes the manifestations, potential mechanisms, epidemiological characteristics, and current interventions related to psychological disorders in LC. Drawing on domestic and international literature, it highlights anxiety, depression, cognitive dysfunction, and post-traumatic stress disorder (PTSD) as the primary psychological symptoms. These symptoms may be associated with neuroinflammation, immune abnormalities, vascular dysfunction, and psychosocial stress. Although research in this area is still developing, psychotherapy, pharmacotherapy, neuromodulation, and lifestyle interventions show promise as treatment approaches. This review aims to provide insights that can inform future research on clinical treatments and psychological care for individuals with LC.},
}
@article {pmid40903751,
year = {2025},
author = {Nguyen, NN and Tissot-Dupont, H and Brouqui, P and Gautret, P},
title = {Post-COVID syndrome in symptomatic COVID-19 patients: a retrospective cohort study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1099},
pmid = {40903751},
issn = {1471-2334},
mesh = {Humans ; Male ; Female ; *COVID-19/complications/epidemiology ; Retrospective Studies ; Middle Aged ; Adult ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Aged ; Prevalence ; Fever/epidemiology ; Headache/epidemiology ; Olfaction Disorders/epidemiology ; },
abstract = {BACKGROUND: Although post-COVID symptoms have been documented in the literature, the risk factors and time required for full recovery remain unclear. We conducted a retrospective analysis of medical records of COVID-19 patients to investigate the prevalence of symptoms after an acute episode of COVID-19 and the risk factors for persistence of symptoms.<br><br>METHODS: This retrospective cohort study analysis examined hospital records of post-COVID individuals with previously confirmed or probable SARS-CoV-2 infection and endurring symptom continuation for at least 3 months post-infection or presenting new symptoms persisting for at least 2 months. Follow-up was conducted during at least six months to access longer-term outcomes. The majority of patients received specialized examination and at least two medical examinations. Descriptive and logistic regression analysis was applied to determine the prevalence and risk factors for post-COVID syndrom.<br><br>RESULT: The mean age of the 319 patients was 47.74&#x2009;&#xb1;&#x2009;11.61 years, and 225 (70.1%) were female. Of the 250/319 patients for whom information on acute infection was available; fever (60.8%), smell disorder (60.8%), asthenia (60.4%) and headache (59.2%) were the most frequent symptoms. The most frequent persisting symptoms were neurological (84.6%), asthenia (80.9%) and cardiac-respiratory symptoms (67.4%). About 80-81% patients reported symptom improvement at six to twelve months of follow-up. Being male and having fever or taste disorders during the acute phase of COVID-19 were independent risk factors for the persistence of long COVID symptoms.<br><br>CONCLUSION: These results could possibly serve to identify patients at a higher risk for the persistence of long COVID symptoms and target them for reinforced therapeutic measures.},
}
@article {pmid40901355,
year = {2025},
author = {Colgan, DD and Stadler, DD and Hope, AA and Zwickey, H and Davenport, TE and Weimbs, T},
title = {Clinically Meaningful Improvements in Long COVID Symptoms Following Ketogenic Metabolic Therapy Combined with Lifestyle Interventions-A Clinical Case Report and Review of the Literature.},
journal = {Case reports in clinical medicine},
volume = {14},
number = {8},
pages = {391-410},
pmid = {40901355},
issn = {2325-7075},
support = {R90 AT008924/AT/NCCIH NIH HHS/United States ; T90 AT008544/AT/NCCIH NIH HHS/United States ; },
abstract = {Approximately 400 million individuals globally are estimated to suffer from Long COVID, an infection-associated chronic condition that occurs after SARS-CoV-2 infection. Despite the high burden, there are no evidence-based or FDA-approved interventions to treat the condition. Given its complexity, a multicomponent approach grounded in a whole-person health model is likely required. This case report highlights clinically meaningful improvements in multiple Long COVID symptoms following a remotely-delivered, ketogenic metabolic therapy combined with group health coaching. Nutritional interventions were paired with exercises to stabilize circadian rhythms and introduce mindfulness-based practices. A review of the literature provides evidence in support of ketogenic metabolic therapy and lifestyle interventions as strategies to target proposed underlying mechanisms of Long COVID and foster stress resilience, thus reducing symptoms and improving quality of life. Findings support future research to optimize and evaluate multimodal nutritional and lifestyle interventions for Long COVID.},
}
@article {pmid40900636,
year = {2025},
author = {Pokharel, BR and Majumdar, N and Williams, F and Dickerson, A and Croy, H and Eells, JB and Didonna, A and Sriramula, S and Cook, PP and Akula, SM},
title = {SARS-CoV-2 infection of substantia nigra pars compacta induces expression of miR-330-5p at 10 days post-infection.},
journal = {The Journal of general virology},
volume = {106},
number = {9},
pages = {},
pmid = {40900636},
issn = {1465-2099},
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; Mice ; *COVID-19/genetics/virology/pathology/metabolism ; Humans ; Mice, Transgenic ; *SARS-CoV-2 ; Angiotensin-Converting Enzyme 2/genetics ; *Substantia Nigra/virology/metabolism/pathology ; Microglia ; Disease Models, Animal ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been linked to several neurological symptoms in coronavirus disease 2019 (COVID-19) patients; however, the molecular mechanisms underlying virus-induced neuroinflammation are not well identified. For example, the effect of SARS-CoV-2 infection of the substantia nigra pars compacta (SNpc) of the midbrain has not been addressed, in spite of its importance in dopaminergic signalling and neurodegenerative abnormalities. The purpose of this study was to understand the SARS-CoV-2-induced inflammatory response in the SNpc region of the brain. We inoculated (intranasally) transgenic mice expressing human ACE2 under control of the human keratin 18 promoter (K18-hACE-2 mice) with a 4×10[3] TCID50 (mild) dose of SARS-CoV-2. Ten days post-inoculation, SARS-CoV-2 was detected in the SNpc of mice, along with increased levels of IL-1β, B1R and ADAM17, and reduced microglial/macrophage occurrence. miR-330-5p expression was significantly reduced in virus-positive SNpc tissue. Luciferase reporter assays supported ADAM17 as a direct target of miR-330-5p. There was no significant difference in miR-330-5p expression levels in the experimental autoimmune encephalomyelitis mice compared to control mice, demonstrating a crucial role for SARS-CoV-2-induced miR-330-5p in brain pathology. Our study uncovers for the first time that SARS-CoV-2 can invade the SNpc and downregulate miR-330-5p expression levels, causing an enhanced ADAM17 expression and possible neuroinflammatory signalling. The results implicate miR-330-5p as a prospective therapeutic target for alleviating midbrain inflammation associated with SARS-CoV-2 infection.},
}
@article {pmid40900297,
year = {2025},
author = {Ahmad, A and Janjua, NZ and Lix, LM and Warda, N and Fung, DLX and Bhéreur, A and Bobos, P and Carazo, S and Décary, S and Goulding, S and Graves, L and Groot, G and Gross, DP and Manhas, KP and McNaughton, CD and Rahme, E and Sander, B and Sbihi, H and Verma, AA and Quinn, KL},
title = {A national atlas to improve the study of Canadians living with long COVID (post-COVID-19 condition).},
journal = {Canadian journal of public health = Revue canadienne de sante publique},
volume = {},
number = {},
pages = {},
pmid = {40900297},
issn = {1920-7476},
support = {492634/CAPMC/CIHR/Canada ; },
abstract = {OBJECTIVES: To develop a national atlas of (1) Canadian cohorts studying or with the potential to study adults living with long COVID (LC) and (2) harmonize provincial and territorial administrative datasets to facilitate the creation of validated case-ascertainment algorithms and foster national collaboration on LC research.<br><br>METHODS: We conducted a multifaceted environmental scan that included a comprehensive literature search and a survey of members of Canada's national LC research network between August 21, 2023, and November 10, 2023. We identified provincial and territorial cohorts, including those that were linkable to administrative data and common data elements among administrative datasets.<br><br>RESULTS: We included 19 Canadian cohorts from five provinces (Alberta, British Columbia, Manitoba, Ontario, and Qu&#xe9;bec) containing data on over 580,000 adults. The majority of the cohorts measured sociodemographic data (e.g., age, sex) and measures of healthcare use, whereas equity-related measures such as gender, ethnicity, and race were limited. There was wide variability in the definitions of LC used across all cohorts. Comparable population-level administrative data are currently available in Alberta, British Columbia, Manitoba, Ontario, Qu&#xe9;bec, New Brunswick, Newfoundland and Labrador, Nova Scotia, and Saskatchewan.<br><br>CONCLUSION: Canada has a rich repository of LC datasets that are limited by variable definitions of LC and inadequate equity-related measures such as gender, ethnicity, and race. Standardization and diversification of these measures will facilitate efforts to study healthcare use and develop health policy to improve the care of Canadian adults living with LC at a population level.},
}
@article {pmid40898520,
year = {2025},
author = {Bai, W and Li, F},
title = {Regulation of m7G methylation in long COVID: Expression profiles and early predictive value of key genes.},
journal = {Medicine},
volume = {104},
number = {35},
pages = {e44209},
pmid = {40898520},
issn = {1536-5964},
support = {2023D01C140//Xinjiang Uygur Autonomous Region Natural Science Foundation/ ; },
mesh = {Humans ; *COVID-19/genetics ; Gene Expression Profiling ; *Guanosine/analogs &amp; derivatives/metabolism ; SARS-CoV-2 ; *DNA Methylation ; Protein Interaction Maps ; Transcriptome ; },
abstract = {Long COVID (LC) poses ongoing public health challenges due to its persistent symptoms following severe acute respiratory syndrome coronavirus 2 infection. Early identification of at-risk individuals remains difficult, and molecular biomarkers are urgently needed. This study aimed to explore the role of N7-methylguanosine (m7G) methylation-related regulatory genes in LC pathogenesis and to develop a predictive model for early detection. Gene expression profiles of LC patients were obtained from the GEO database (GSE224615), and differentially expressed genes (DEGs) were identified. These DEGs were intersected with m7G regulatory genes to identify LC-specific candidates. A protein-protein interaction network was constructed to identify hub genes, and enrichment analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were performed to investigate the biological relevance of the identified genes. Immune cell infiltration analyses were conducted to explore the immunological features associated with candidate genes. Findings were validated using an external dataset (GSE217948). A clinical prediction model was constructed using Least absolute shrinkage and selection operator regression followed by logistic regression, and evaluated via receiver operating characteristic curve, calibration, and decision curve analysis. A total of 65 DEGs were identified in LC patients, comprising 44 up-regulated and 21 down-regulated genes. Thirty genes overlapped with the m7G regulatory gene set. Functional enrichment revealed significant involvement in pathways such as FceRI-mediated NF-κB activation and platelet aggregation. Correlation analysis showed that several m7G-related genes were associated with altered immune cell infiltration patterns. The external dataset confirmed the reproducibility of gene expression trends. Seven core genes were ultimately selected to build the predictive model, which demonstrated robust performance in distinguishing LC patients from controls. This study highlights the importance of m7G methylation in LC pathogenesis and uncovers novel immune-related mechanisms underlying its persistence. The predictive model based on m7G-related markers provides a promising tool for early LC identification and may inform future diagnostic and therapeutic strategies.},
}
@article {pmid40897497,
year = {2025},
author = {McDuff, K and Bhéreur, A and Kadakia, Z and Corrales-Medina, VF and Gross, DP and Janaudis-Ferreira, T and Lam, G and Naik, H and Paterson, TSE and Sanchez-Ramirez, DC and Sasseville, M and Sekar, A and Vohra, S and Bayley, M and Birch, S and Busse, JW and Cameron, JI and Kaup, C and Cheung, A and Churchill, K and Edgell, H and Goulding, S and Hamilton, C and Jaglal, S and Kumar, P and Levin, A and Munblit, D and Naye, F and O'Hara, M and Plaismond, J and Rutledge, M and Supper, JW and Quinn, K and Wasilewski, MB and Wilkins, A and O'Brien, KK},
title = {Establishing a framework of measurement for use in Long COVID research and practice: protocol for a scoping review involving evidence review and consultation.},
journal = {BMJ open},
volume = {15},
number = {9},
pages = {e094497},
pmid = {40897497},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/therapy ; Scoping Reviews as Topic ; Caregivers ; SARS-CoV-2 ; Research Design ; *Outcome Assessment, Health Care/methods ; Child ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Our aim is to develop a Framework of Measurement for people living with Long COVID and their caregivers for use in Long COVID research and clinical practice. Specifically, we will characterise evidence pertaining to outcome measurement and identify implementation considerations for use of outcome measures among adults and children living with Long COVID and their caregivers.<br><br>METHODS AND ANALYSIS: We will conduct a scoping study involving: (1) an evidence review and (2) a two-phased consultation, using methodological steps outlined by the Arksey and O'Malley Framework and Joanna Briggs Institute. We will answer the following question: What is known about outcome measures used to describe, evaluate or predict health outcomes among adults and children living with Long COVID and their caregivers?<br><br>EVIDENCE REVIEW: we will review peer review published and grey literature to identify existing outcome measures and their reported measurement properties with people living with Long COVID and their caregivers. We will search databases including MEDLINE, Embase, CINAHL, PsycINFO and Scopus for articles published since 2020. Two authors will independently review titles and abstracts, followed by full text to select articles that discuss or use outcome measures for Long COVID health outcomes, pertain to adults or children living with Long COVID and/or their caregivers and are based in research or clinical settings. We will extract data including article characteristics, terminology and definition of Long COVID, health outcomes assessed, characteristics of outcome measures, measurement properties and implementation considerations. We will collate and summarise data to establish a preliminary Framework of Measurement. Consultation phase 1: we will conduct an environmental scan involving a cross-sectional web-based questionnaire among individuals with experience using or completing outcome measures for Long COVID, to identify outcome measures not found in the evidence review and explore implementation considerations for outcome measurement in the context of Long COVID. Consultation phase 2: we will conduct focus groups to review the preliminary Framework of Measurement and to highlight implementation considerations for outcome measurement in Long COVID. We will analyse questionnaire and focus group data using descriptive and content analytical approaches. We will refine the Framework of Measurement based on the focus group consultation using community-engaged approaches with the research team.<br><br>ETHICS AND DISSEMINATION: Protocol approved by the University of Toronto Health Sciences Research Ethics Board (protocol #46503) for the consultation phases of the study. Outcomes will include a Framework of Measurement, to enhance measurement of health outcomes in Long COVID research and clinical practice. Knowledge translation will also occur in the form of publications and presentations.},
}
@article {pmid40895196,
year = {2025},
author = {Eltoum, AI and Begum, R and Gold, LS and Patel, PB and Andrews, JS},
title = {Exploring the Associations between Self-Reported Sleep Disturbance and Cognitive Impairment among Survivors of COVID-19 Hospitalization.},
journal = {Mental health science},
volume = {3},
number = {3},
pages = {},
pmid = {40895196},
issn = {2642-3588},
support = {K23 AG058756/AG/NIA NIH HHS/United States ; },
abstract = {STUDY OBJECTIVES: Cognitive impairment following COVID-19 infection is common and risk factors remain poorly understood. Sleep disturbance increases risk of cognitive impairment in the general population, and sleep disturbance is common after COVID-19. While prior literature has extensively explored the relationship between sleep and cognition, few studies have addressed the temporality of this association and how one may contribute to the other over time. This study assessed whether new sleep disturbance at 1-month is associated with risk of cognitive impairment at 6-months after COVID-19 hospitalization.<br><br>METHODS: English-speaking adults aged &#x2265;18 years at the University of Washington Medical Center who survived to 1-month post-COVID-19 hospitalization were enrolled. Self-reported sleep disturbance, cognitive function, cognitive abilities, and fatigue severity at 1- and 6-months after discharge were assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS[&#xae;]) short forms. Linear and logistic regression models analyzed associations of new sleep disturbance at 1-month with cognitive function, cognitive abilities, and fatigue severity outcomes at 6-months.<br><br>RESULTS: Participants (n=120) had mean age of 56.5&#xb1;15.7 years, and 35% developed new sleep disturbance at 1-month. Among those with versus without new sleep disturbance at 1-month, 74% versus 40%, 76% versus 37%, and 64% versus 50% developed significant worsening in cognitive function, cognitive abilities, and fatigue severity at 6 months, respectively.<br><br>CONCLUSIONS: In this single-center observational cohort, new sleep disturbance at 1-month post-COVID-19 hospitalization was associated with subsequent significant worsening in cognitive function, cognitive abilities, and fatigue severity at 6-months. Thus, new sleep disturbance may be a risk factor for persistent neurocognitive impairment after COVID-19. Additional studies should validate these relationships and examine whether improving sleep quality may reduce the risk of cognitive impairment in these patients.},
}
@article {pmid40894595,
year = {2025},
author = {Kwissa, M and Mathayan, M and Salunkhe, SS and Bakthavachalam, V and Ye, Z and Sanborn, MA and Condo, S and Upadhye, A and Nemakal, A and Richner, JM and Basu, S and Novak, RM and Jacobson, JR and Ganesh, BB and Cerda, M and Utz, PJ and Krishnan, JA and Prabhakar, BS and Rehman, J},
title = {Persistent Immune Dysregulation during Post-Acute Sequelae of COVID-19 is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40894595},
issn = {2692-8205},
support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; },
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome or "Long COVID" represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of PASC, but the extent of PASC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed PASC. Compared to convalescent, PASC participants with a broad range of PASC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the PASC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis, we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa-associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in PASC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in PASC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity.},
}
@article {pmid40894471,
year = {2025},
author = {Dias Rodrigues, G and Fazan, R and Montano, N},
title = {Editorial: Updates on cardiovascular variability: underlying mechanisms and non-pharmacological therapeutic targets.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1670996},
pmid = {40894471},
issn = {2297-055X},
}
@article {pmid40894014,
year = {2025},
author = {Abramoff, B and Dillingham, T and Rybicki, AK and Shofer, F and McGinley, E and Verma, SS and Kuns, MC and Barry, JT and Pezzin, LE},
title = {Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program to Improve the Functioning of Persons Suffering from Post-acute Sequelae of SARS-CoV-2 infection (PASC): A Randomized Controlled Trial.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40894014},
issn = {2693-5015},
support = {R01 HD108312/HD/NICHD NIH HHS/United States ; },
abstract = {BACKGROUND: About 10-20% of persons who contract SARS CoV-2 will experience persistent post-acute sequelae of SARSCoV-2 infection (referred here as PASC). Given that persistent symptoms are heterogeneous with multisystem involvement, recent consensus recommendations suggest that a holistic rehabilitation program may be required to manage PASC and restore function. While treatments offered at emerging outpatient COVID recovery clinics are being informed by previous similar diseases, the need is great for a better understanding of the unique needs of this growing population and for tested, efficacious rehabilitation programs to address them.<br><br>METHODS/DESIGN: Data from a large and diverse ongoing longitudinal survey of persons positive for COVID-19 at the study health system will serve as the sampling frame from which to enroll PASC study patients. The targeted six-week program will comprise a core set of therapies including individually titrated isometrics, strengthening of accessory breathing muscles and diaphragm, resistance and aerobic conditioning, and neuropsychological and cognitive remediation tailored to patients' needs. Using a randomized controlled trial design, the effectiveness of the supervised multimodal rehabilitation intervention will be compared to that of a self-guided (active control) group receiving patient education materials adapted from the World Health Organization guidelines for PASC management. In addition to walking speed, a widely used global measure of aerobic capacity and endurance, and patient-reported health and functioning (primary outcomes), we will assess intervention effectiveness on: cognitive functioning, pain, fatigue, tension, stress, anxiety, and depression, and self-management of PASC symptoms (secondary outcomes). Outcomes will be measured at 8 weeks and at 90 day's post- study entry to examine sustainability of effects. Recruitment is ongoing.<br><br>DISCUSSION: It is unlikely that COVID-19 vaccines will lead to the end of PASC syndrome given the emergence of increasingly infectious variants and the high numbers of individuals with continued symptoms several months from initial infection. High rates of vaccine hesitancy and refusal will also contribute to the persistence of both COVID-19 and PASC. Given the dearth of rigorous scientific evidence regarding effective assessment and treatment of PASC and unresolved questions concerning post-COVID rehabilitation care, the results of this study will have significant implications for both policy and program development.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06156202.},
}
@article {pmid40893436,
year = {2025},
author = {Zeng, J and Jia, X},
title = {Quantifying compatibility mechanisms in traditional Chinese medicine with interpretable graph neural networks.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {8},
pages = {101342},
pmid = {40893436},
issn = {2214-0883},
abstract = {Traditional Chinese medicine (TCM) features complex compatibility mechanisms involving multi-component, multi-target, and multi-pathway interactions. This study presents an interpretable graph artificial intelligence (GraphAI) framework to quantify such mechanisms in Chinese herbal formulas (CHFs). A multidimensional TCM knowledge graph (TCM-MKG; https://zenodo.org/records/13763953) was constructed, integrating seven standardized modules: TCM terminology, Chinese patent medicines (CPMs), Chinese herbal pieces (CHPs), pharmacognostic origins (POs), chemical compounds, biological targets, and diseases. A neighbor-diffusion strategy was used to address the sparsity of compound-target associations, increasing target coverage from 12.0% to 98.7%. Graph neural networks (GNNs) with attention mechanisms were applied to 6,080 CHFs, modeled as graphs with CHPs as nodes. To embed domain-specific semantics, virtual nodes medicinal properties, i.e., therapeutic nature, flavor, and meridian tropism, were introduced, enabling interpretable modeling of inter-CHP relationships. The model quantitatively captured classical compatibility roles such as "monarch-minister-assistant-guide," and uncovered TCM etiological types derived from diagnostic and efficacy patterns. Model validation using 215 CHFs used for coronavirus disease 2019 (COVID-19) management highlighted Radix Astragali-Rhizoma Phragmitis as a high-attention herb pair. Mass spectrometry (MS) and target prediction identified three active compounds, i.e., methylinissolin-3-O-glucoside, corydalin, and pingbeinine, which converge on pathways such as neuroactive ligand-receptor interaction, xenobiotic response, and neuronal function, supporting their neuroimmune and detoxification potential. Given their high safety and dietary compatibility, this herb pair may offer therapeutic value for managing long COVID-19. All data and code are openly available (https://github.com/ZENGJingqi/GraphAI-for-TCM), providing a scalable and interpretable platform for TCM mechanism research and discovery of bioactive herbal constituents.},
}
@article {pmid40892700,
year = {2025},
author = {Jothi, S and Insel, M and Claessen, G and Kubba, S and Howden, EJ and Ruiz-Carmona, S and Levine, T and Rischard, FP},
title = {Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.},
journal = {Physiological reports},
volume = {13},
number = {17},
pages = {e70535},
pmid = {40892700},
issn = {2051-817X},
mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/metabolism ; *COVID-19/physiopathology/complications ; Male ; Female ; Oxygen Consumption ; Adult ; Middle Aged ; Muscle, Skeletal/metabolism/physiopathology ; *Exercise Tolerance ; Exercise Test ; *Exercise/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Post-acute sequelae of SARS-CoV-2 (PASC or "long COVID") and chronic fatigue syndrome/myalgic encephalitis (CFS/ME) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 PASC patients, 11 CFS/ME patients, and 11 controls. We evaluated the contributions of alveolar ventilation (V̇a), lung diffusion capacity (DL), cardiac output (Q̇), skeletal muscle diffusion capacity (DM), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (Vmax) to peak oxygen consumption (V̇O2peak). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V̇O2peak. V̇O2peak was significantly reduced in both PASC and CFS/ME compared to controls. Skeletal muscle O2 diffusion (DM) was the most impaired parameter in both patient groups (p = 0.01). Correcting DM alone improved V̇O2 by 66% in PASC (p = 0.008) and 34.7% in CFS/ME (p = 0.06), suggesting a dominant role for peripheral O2 extraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (DM) is a shared mechanism of exercise intolerance in PASC and CFS/ME and may represent a therapeutic target. However, our findings are limited by small sample size.},
}
@article {pmid40887598,
year = {2025},
author = {Klein, DO and Wilmes, N and Waardenburg, SF and Bonsel, GJ and Birnie, E and Wintjens, MS and Heemskerk, SC and Janssen, EB and Ghossein-Doha, C and Warlé, MC and Jacobs, LM and Hemmen, B and Verbunt, JA and van Bussel, BC and van Santen, S and Kietselaer, BL and Jansen, G and Asselbergs, FW and Linschoten, M and Haagsma, JA and van Kuijk, SMJ and , },
title = {Development and internal validation of a prediction model for post-COVID-19 condition 2 years after infection-results of the CORFU study.},
journal = {Diagnostic and prognostic research},
volume = {9},
number = {1},
pages = {18},
pmid = {40887598},
issn = {2397-7523},
support = {2020B006 CAPACITY//Dutch Heart Foundation/ ; 2020B006 CAPACITY//Dutch Heart Foundation/ ; 10430102110006 DEFENCE//The Netherlands Organization for Health Research and Development (ZonMW)/ ; 10430102110006 DEFENCE//The Netherlands Organization for Health Research and Development (ZonMW)/ ; },
abstract = {BACKGROUND: A subset of COVID-19 patients develops post-COVID-19 condition (PCC). This condition results in disability in numerous areas of patients' lives and a reduced health-related quality of life, with societal impact including work absences and increased healthcare utilization. There is a scarcity of models predicting PCC, especially those considering the severity of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and incorporating long-term follow-up data. Therefore, we developed and internally validated a prediction model for PCC 2 years after SARS-CoV-2 infection in a cohort of COVID-19 patients.<br><br>METHODS: Data from the CORona Follow-Up (CORFU) study were used. This research initiative integrated data from multiple Dutch COVID-19 cohort studies. We utilized 2-year follow-up data collected via the questionnaires between October 1st of 2021 and December 31st of 2022. Participants were former COVID-19 patients, approximately 2-year post-SARS-CoV-2 infection. Candidate predictors were selected based on literature and availability across cohorts. The outcome of interest was the prevalence of PCC at 2&#xa0;years after the initial infection. Logistic regression with backward stepwise elimination identified significant predictors such as sex, BMI and initial disease severity. The model was internally validated using bootstrapping. Model performance was quantified as model fit, discrimination and calibration.<br><br>RESULTS: In total 904 former COVID-19 patients were included in the analysis. The cohort included 146 (16.2%) non-hospitalized patients, 511 (56.5%) ward admitted patients, and 247 (27.3%) intensive care unit (ICU) admitted patients. Of all participants, 551 (61.0%) participants suffered from PCC. We included 20 candidate predictors in the multivariable analysis. The final model, after backward elimination, identified sex, body mass index (BMI), ward admission, ICU admission, and comorbidities such as arrhythmia, asthma, angina pectoris, previous stroke, hernia, osteoarthritis, and rheumatoid arthritis as predictors of post-COVID-19 condition. Nagelkerke's R-squared value for the model was 0.19. The optimism-adjusted AUC was 71.2%, and calibration was good across predicted probabilities.<br><br>CONCLUSIONS: This internally validated prediction model demonstrated moderate discriminative ability to predict PCC 2&#xa0;years after COVID-19 based on sex, BMI, initial disease severity, and a collection of comorbidities.},
}
@article {pmid40889165,
year = {2025},
author = {Gomez-Bravo, R and León-Herrera, S and Guisado-Clavero, M and Gefaell, I and Wostmann, X and Wössner, N and Vinker, S and Vassallo La Ferla, F and Kırkoç Üçüncü, E and Tsigarovski, G and Torzsa, P and Suija, K and Stepanović, A and Sentker, T and Segernäs, A and Seifert, B and Sánchez-Castro, M and Schneider, JG and Repovská, A and Petrazzuoli, F and Petek, D and Perjes, A and Parodi López, N and Neves, AL and Nessler, K and Muris, J and Mortsiefer, A and Moreels, S and Meister, T and Mäntyselkä, P and Murauskienė, L and Lingner, H and Krztoń-Królewiecka, A and Kostic, M and Çimen Korkmaz, B and Knezevic, S and Kazakos, S and Karathanos, V and Shushman, I and Ilkov, O and Hoffmann, K and Heleno, B and Hanževački, M and Gjorgjievski, D and Frese, T and Fournier, M and Fitzgerald, L and Feldmane, S and Dotsenko, M and Domeyer, PR and Croucher, D and Cerny, V and Burgers, JS and Brutskaya-Stempkovskaya, E and Busneag, CI and Buono, N and Bensemmane, S and Bayen, S and Bakola, M and Assenova, R and Adler, L and Ares-Blanco, S and Astier Peña, MP},
title = {Towards consensus: The need for standardised definitions in Long (post) COVID care in 34 European countries.},
journal = {The European journal of general practice},
volume = {31},
number = {1},
pages = {2535618},
pmid = {40889165},
issn = {1751-1402},
mesh = {Humans ; *COVID-19/therapy/diagnosis/epidemiology ; Europe/epidemiology ; Retrospective Studies ; Consensus ; SARS-CoV-2 ; *Terminology as Topic ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: The COVID-19 pandemic has significantly impacted global healthcare systems, leading to challenges in managing Long COVID. Variations in definitions and diagnostic criteria across Europe hinder recognition and treatment efforts. This study aims to analyse and compare the definitions of Long COVID used in 34 European countries.<br><br>METHODS: A retrospective descriptive study was conducted involving key informants from 34 European countries, utilising an online questionnaire to gather data on Long COVID definitions. Quantitative and qualitative analyses were employed to assess the variability of definitions and challenges in managing Long COVID.<br><br>RESULTS: The study found significant variation in Long COVID definitions among the participating countries; the most frequent definition was the other definition (n: 17, 50.0%), followed by the World Health Organisation's definition (n: 16, 47.0%) and the CDC definition (n: 11, 32.3%). Half of the countries reported using multiple definitions simultaneously, indicating a lack of standardisation. Qualitative analyses highlighted challenges such as difficulties in standardising terminology, variability in clinical criteria, and issues with implementing diagnostic codes.<br><br>CONCLUSION: The findings underscore the need for a unified, yet adaptable, definition of Long COVID. Such a definition would support general practitioners (GPs) by simplifying diagnostic processes, improving continuity of care, and facilitating equitable patient access to multidisciplinary resources. The current lack of consensus complicates patient care, data collection, and resource allocation, impacting health policy development. Future efforts should focus on achieving agreement on definitions to ensure equitable treatment and effective healthcare responses to Long COVID.},
}
@article {pmid40888500,
year = {2025},
author = {Fain, MJ and Horne, BD and Horwitz, LI and Thaweethai, T and Greene, M and Hornig, M and Orkaby, AR and Rosen, C and Ritchie, CS and Ashktorab, H and Blachman, N and Brim, H and Emerson, S and Erdmann, N and Erlandson, KM and de Erausquin, G and Fong, T and Geng, LN and Gordon, HS and Gully, JR and Hadlock, J and Han, J and Huang, W and Jagannathan, P and Kelly, JD and Klein, JD and Krishnan, JA and Levitan, EB and McComsey, GA and McDonald, D and Montgomery, AP and O'Brien, L and Ofotokun, I and Patterson, TF and Peluso, MJ and Pemu, P and Perlowski, A and Reiman, EM and Sanon, M and Seshadri, S and Shellito, J and Sherif, ZA and Shikuma, C and Singer, NG and Singh, U and Trinity, JD and Wisnivesky, J and Witvliet, MG and Foulkes, A and Nikolich, J&#x17d; and , },
title = {Age-Related Changes in the Clinical Picture of Long COVID.},
journal = {Journal of the American Geriatrics Society},
volume = {73},
number = {10},
pages = {3123-3137},
pmid = {40888500},
issn = {1532-5415},
support = {R01 AG082541/AG/NIA NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UM1TR004528/TR/NCATS NIH HHS/United States ; P30AG066546/AG/NIA NIH HHS/United States ; P30 AG066546/AG/NIA NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; P30AG072980/AG/NIA NIH HHS/United States ; R56AG074467/AG/NIA NIH HHS/United States ; UM1TR004409/TR/NCATS NIH HHS/United States ; R56 AG074467/AG/NIA NIH HHS/United States ; OT2HL161841/HL/NHLBI NIH HHS/United States ; //William Randolph Hearst Foundations/ ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; P30 AG072980/AG/NIA NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; //O. Wayne Rollins Foundation/ ; },
mesh = {Humans ; Male ; Middle Aged ; Female ; *COVID-19/complications/epidemiology/physiopathology ; Aged ; Adult ; Age Factors ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Adolescent ; *Aging/physiology ; Young Adult ; Aged, 80 and over ; Prevalence ; Independent Living ; },
abstract = {BACKGROUND: This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID.<br><br>METHODS: We analyzed community-dwelling participants &#x2265;&#x2009;60&#x2009;years old (2662 with prior infection, 461 controls) compared to participants 18-59&#x2009;years (7549 infected, 728 controls) in the Researching COVID to Enhance Recovery adult (RECOVER-Adult) cohort &#x2265;&#x2009;135&#x2009;days post-onset.<br><br>RESULTS: Compared to the Age 18-39 group, the adjusted odds of LCRI &#x2265;&#x2009;12 were higher for the Age 40-49 group (odds ratio [OR]&#x2009;=&#x2009;1.40, 95% confidence intervals [CI]&#x2009;=&#x2009;1.21-1.61, p&#x2009;<&#x2009;0.001) and 50-59 group (OR&#x2009;=&#x2009;1.31, CI&#x2009;=&#x2009;1.14-1.51, p&#x2009;<&#x2009;0.001), similar for the Age 60-69 group (OR&#x2009;=&#x2009;1.09, CI&#x2009;=&#x2009;0.93-1.27, p&#x2009;=&#x2009;0.299), and lower for the &#x2265;&#x2009;70 group (OR&#x2009;=&#x2009;0.68, CI&#x2009;=&#x2009;0.54-0.85, p&#x2009;<&#x2009;0.001). Participants &#x2265;&#x2009;70&#x2009;years had smaller adjusted differences between infected and uninfected symptom prevalence rates than those aged 18-39 for the following symptoms: hearing loss, fatigue, pain (including joint, back, chest pain and headache), post-exertional malaise, sleep disturbance, hair loss, palpitations, and sexual desire/capacity, making these symptoms less discriminating for Long COVID in older adults than in younger. Symptom clustering, as described in Thaweethai et&#xa0;al. (JAMA 2023) also exhibited age-related shifts: clusters 1 (anosmia and ageusia) and 2 (gastrointestinal, chronic cough and palpitations, without anosmia, ageusia or brain fog) were more likely, and clusters 3 (brain fog, but no loss of smell or taste) and 4 (a mix of symptoms) less likely to be found in older adults (relative risk ratios for clusters 3-4 ranging from 0.10-0.34, p&#x2009;<&#x2009;0.001 vs. 18-39&#x2009;year-olds).<br><br>CONCLUSIONS: Within the limits of this observational study, we conclude that in community-dwelling older adults, aging alters the prevalence and pattern of reported Long COVID.},
}
@article {pmid40887959,
year = {2025},
author = {Parums, DV},
title = {Editorial: Dormant Cancer Cells, Cancer Progression, and Post-Acute Sequelae of COVID-19 and Influenza.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {31},
number = {},
pages = {e951178},
pmid = {40887959},
issn = {1643-3750},
mesh = {*COVID-19/complications/pathology ; Humans ; *Influenza, Human/complications/pathology ; Animals ; SARS-CoV-2 ; *Neoplasms/pathology/virology ; Disease Progression ; Mice ; Post-Acute COVID-19 Syndrome ; },
abstract = {Since the COVID-19 pandemic, vaccine uptake has fallen, and awareness of the long-term consequences of respiratory virus infections, particularly long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has also lost momentum. After a decade of declining mortality rates from cancer in the US, from 2020, registered age-standardized cancer-related deaths and mortality increased for all cancers. Cancer cell 'dormancy' results from an equilibrium between tumor cell division and apoptosis, and provides an explanation for relapse and metastasis that can occur months, years, or decades after treatment. In July 2025, findings from a study in mice infected with influenza and SARS-CoV-2 showed the rapid loss of the pro-dormancy phenotype in breast carcinoma cells in the lung, and expansion of metastatic carcinoma cells within weeks. Animal model findings support findings in cancer survivors that SARS-CoV-2 infection was significantly associated with an increased risk of lung metastasis and cancer-related mortality. This Editorial aims to highlight findings from real-world population studies on the association between COVID-19 and cancer and new experimental findings for how SARS-CoV-2, influenza, and possibly other respiratory viruses may 'awaken' dormant cancer cells.},
}
@article {pmid40887815,
year = {2025},
author = {Chaichana, U and Man, KKC and Ju, C and Makaronidis, J and Wei, L},
title = {Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf429},
pmid = {40887815},
issn = {1537-6591},
abstract = {BACKGROUND: A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post-COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.<br><br>OBJECTIVES: To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection.<br><br>DESIGN: A retrospective cohort study using a sequential target trial emulation framework.<br><br>DATA SOURCES: The United Kingdom primary care data from the Clinical Practice Research Datalink Aurum database from March 2020 to July 2023.<br><br>PARTICIPANTS: Adults with overweight or obesity (body mass index &#x2265; 25&#x2005;kg/m&#xb2;) and a record of severe acute respiratory syndrome coronavirus 2 infection were included. Exclusions included metformin use in the prior year or metformin contraindications.<br><br>MEASUREMENTS: The outcome was PCC, defined by a PCC diagnostic code or at least 1 World Health Organization-listed symptoms between 90 and 365 days after diagnosis, with no prior history of the symptom within 180 days before infection. The pooled hazard ratio and risk difference for the incidence of PCC were adjust for baseline characteristics.<br><br>RESULTS: Among 624 308 patients, 2976 initiated metformin within 90 days of COVID-19 diagnosis. The 1-year risk difference for PCC in the intention-to-treat analysis was -12.58% (hazard ratio 0.36; 95% CI, 0.32-0.41), with consistent results in subgroup analyses.<br><br>LIMITATIONS: Findings may not apply to individuals with a normal body mass index.<br><br>CONCLUSIONS: Early metformin treatment in overweight or obese individuals may reduce PCC risk. Further research is needed to confirm causality and clarify metformin's role in PCC management.},
}
@article {pmid40886878,
year = {2025},
author = {do Nascimento, KF and Alchieri, EF and Sanson, CS and Andrade Cavalli, ME and Moreira Pena, YA and Okumura Tioda, IS and de Oliveira, LE and Arend, J and Duarte, MMMF and Paniz, C and Oliveira, MS and Furian, AF and Freire Royes, LF and Fighera, MR},
title = {Neuroinflammation in long COVID: the role of the Val16Ala polymorphism of SOD2 and cognitive impairment.},
journal = {Neuroscience},
volume = {585},
number = {},
pages = {418-428},
doi = {10.1016/j.neuroscience.2025.08.047},
pmid = {40886878},
issn = {1873-7544},
mesh = {Humans ; Male ; Female ; *COVID-19/complications/genetics/psychology ; *Cognitive Dysfunction/genetics/etiology ; Adult ; Polymorphism, Single Nucleotide ; *Superoxide Dismutase/genetics ; Young Adult ; *Neuroinflammatory Diseases/genetics ; Cytokines/blood ; Genetic Predisposition to Disease ; Neuropsychological Tests ; Superoxide Dismutase 2 ; },
abstract = {Long COVID (LC) includes persistent behavioral and cognitive deficits, impacting quality of life. Neuroinflammation plays a key role in these alterations, with genetic factors influencing susceptibility. The MnSOD Val16Ala SNP is associated with neuroinflammation and cognitive dysfunction, but its role in LC remains unclear. This study investigated the relationship between the SOD2 Val16Ala polymorphism and neurocognitive alterations in young adults post-SARS-CoV-2 infection. Neurocognitive performance was assessed using the Neupsilin test in individuals with and without prior COVID-19. Blood samples were collected for the quantification of cytokines (IL-1, IL-6, TNF-α, and IFN-γ) and for the genotyping of the SOD2 Val16Ala polymorphism. The COVID-19 group showed worse cognitive performance and higher cytokine levels than controls, particularly in memory and executive function. Val allele carriers (Val/Ala and Val/Val) exhibited increased pro-inflammatory cytokine levels compared to Ala/Ala carriers. These findings suggest a potential interaction between genetic susceptibility and inflammatory response in post-COVID neurocognitive alterations. Young adults post-COVID-19 presented an exacerbated neuroinflammatory response, likely influencing cognition. The presence of the Val allele was associated with greater susceptibility to inflammatory events, suggesting a genetic component in LC-related neurological dysfunction. These results reinforce the role of neuroinflammation in LC and highlight the importance of genetic factors in determining cognitive outcomes. Understanding these mechanisms may help identify individuals at higher risk and support future therapeutic strategies.},
}
@article {pmid40883052,
year = {2025},
author = {Mizuno, A},
title = {Stirring the POTS: Finding Symptom Patterns in Long COVID.},
journal = {JACC. Advances},
volume = {4},
number = {8},
pages = {101869},
pmid = {40883052},
issn = {2772-963X},
}
@article {pmid40883051,
year = {2025},
author = {Al Mouslmani, M and Sawano, M and Arun, AS and Wu, Y and Shah, RM and Kaleem, S and Zhou, T and Murugiah, K and Lu, Y and Herrin, J and Bishop, P and Taub, P and Peixoto, AJ and Bhattacharjee, B and Iwasaki, A and Krumholz, HM},
title = {Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study.},
journal = {JACC. Advances},
volume = {4},
number = {8},
pages = {101873},
pmid = {40883051},
issn = {2772-963X},
support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID.<br><br>OBJECTIVES: The purpose of this study was to describe the experience of people reporting long COVID-associated POTS.<br><br>METHODS: We collected data from individuals aged &#x2265;18 years with self-reported long COVID who participated in the Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) cohort, an online observational study. The study included participants surveyed from May 2022 to July 2023. POTS status was determined by self-reported diagnosis of POTS. We compared the demographics, symptoms, associated conditions, and health status of people with and without self-reported POTS.<br><br>RESULTS: Of the 578 individuals included, 167 (28.9%) reported new-onset POTS and 411 (71.1%) did not report POTS as one of their long COVID-associated conditions. Seventy-eight percent of participants with self-reported POTS were women (range, 18-74 years). Participants with self-reported POTS were younger, had more financial difficulties, more social isolation, more suicidal thoughts, worse health status measured by the EuroQoL visual analog scale, and reported higher rates of rapid heart rate after standing up, dizziness, palpitations, persistent chest pain, sudden chest pain, excessive fatigue, exercise intolerance, heat intolerance, brain fog, tinnitus, migraine, internal tremors, skin discoloration, and dry eyes, as well as new-onset myalgic encephalomyelitis/chronic fatigue syndrome and mast cell disorders.<br><br>CONCLUSIONS: Individuals with self-reported long COVID-associated POTS experienced substantial health burdens in various domains compared with those without self-reported POTS, highlighting the urgency for further research to understand the mechanism, characterize the physiological derangements, and target treatments so we can help these individuals.},
}
@article {pmid40885518,
year = {2025},
author = {Fernández-de-Las-Peñas, C and Ruiz-Ruigómez, M and Esparcia-Pinedo, L and Colom-Fernández, B and Cava-Valenciano, F and Torres-Macho, J and Arrieta-Ortubay, E and Akasbi-Moltalvo, M and Lumbreras-Bermejo, C and Arendt-Nielsen, L and Franco-Moreno, A},
title = {Classic pathway persistent complement activation is associated with specific symptoms in individuals with post-COVID-19 condition: A case-control study.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {159},
number = {},
pages = {108032},
doi = {10.1016/j.ijid.2025.108032},
pmid = {40885518},
issn = {1878-3511},
mesh = {Humans ; *COVID-19/immunology/complications ; Female ; Male ; Case-Control Studies ; Middle Aged ; Adult ; SARS-CoV-2 ; *Complement Pathway, Classical/immunology ; *Complement Activation ; Survivors ; },
abstract = {OBJECTIVES: The complement system is a crucial part of the immune system. The role of complement activation in post-COVID-19 condition is still not conclusive. We present a case-control study investigating long-lasting complement hyperactivation in COVID-19 survivors with/without post-COVID-19 condition.<br><br>METHODS: A case-control (2:1 design) study was performed. Concentration levels of four proteins from classic complement pathway (C3, C4, C5, C7) and total hemolytic complement (CH50) activity were obtained from blood samples in group of survivors with post-COVID-19 condition and in a comparison group of survivors without post-COVID-19 condition, matched by age, sex, and vaccination status. Post-COVID-19 condition was defined when individuals self-reported at least one of these post-COVID-19 symptoms: fatigue, arthralgia, myalgia, memory problems, new-onset headache, or palpitations.<br><br>RESULTS: A total of 57 (56.1% women, age: 46.5 years, SD: 9.0 years) survivors with post-COVID-19 condition and 27 (55.5% women, age: 46.5 years, SD: 11.5 years) survivors without post-COVID-19 condition were evaluated 1.7 (SD 1.2) and 2.0 (SD 1.7) years after SARS-CoV-2 infection, respectively. Overall, the results did not reveal differences in complement protein levels and CH50 activity between survivors with or without post-COVID-19 condition. Patients reporting post-COVID fatigue exhibited lower C3 levels (P = 0.025) than those without post-COVID fatigue, whereas survivors with post-COVID dyspnea reported lower levels of C3 (P = 0.001), C5 (P = 0.015), and C7 (P = 0.030) proteins than those without post-COVID dyspnea.<br><br>CONCLUSIONS: This explorative case-control study did not observe overall complement activation from classic pathway in survivors with post-COVID-19 condition up to 2 years after. Some complement proteins were elevated in individuals with specific post-COVID symptoms, such as fatigue or dyspnea.},
}
@article {pmid40883696,
year = {2025},
author = {Kamal, SM and Al Qahtani, MS and Al Aseeri, A and Naghib, MEDM and Al Mazroua, AMM and Alshamrani, AMM and Al Mazroua, MM and AlHarbi, FSF},
title = {Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1082},
pmid = {40883696},
issn = {1471-2334},
abstract = {PURPOSE: Long COVID-19 is a growing public health concern, but its long-term burden and predictors remain underexplored, particularly in underrepresented populations.<br><br>METHODS: This four-year prospective cohort study was conducted in Saudi Arabia, enrolling adults with confirmed acute COVID-19 from multiple affiliated healthcare centers between March 2020 and March 2024. Of 1,521 screened patients, 816 were enrolled and followed for up to four years (median: 24 months). Per WHO criteria, participants were classified as having long COVID-19 (n&#x2009;=&#x2009;238) or resolved infection (n&#x2009;=&#x2009;578). Demographics, comorbidities, vaccination, reinfection, and acute illness severity were recorded. Health-related quality of life (HRQoL) was assessed using SF-36 and EQ-5D-5&#xa0;L. Logistic regression identified predictors of long COVID-19, and Cox proportional hazards models evaluated time to recovery.<br><br>RESULTS: Fatigue (57.1%), post-exertional malaise (45.8%), cough (41.2%), and cognitive dysfunction (30.7%) were the most common persistent symptoms. Female sex (adjusted OR 11.11; 95% CI: 4.48&#x2013;26.24) and diabetes mellitus (adjusted OR 14.3; 95% CI: 7.0&#x2013;29.4) independently predicted long COVID-19. Delayed recovery was associated with female sex (aHR 3.36; 95% CI: 1.85&#x2013;6.10), diabetes (aHR 1.57; 95% CI: 1.00&#x2013;2.46), reinfection (aHR 1.86; 95% CI: 1.05&#x2013;3.29), and hospitalization (aHR 1.08; 95% CI: 1.01&#x2013;1.16). HRQoL scores remained significantly lower at 6 and 12 months. In the long COVID-19 group, 38.7% of patients normally resumed work within 12 months, compared to 82.3% in the resolved COVID-19 group.<br><br>CONCLUSIONS: Nearly 29% of post-acute COVID-19 patients developed long COVID-19 in this Middle Eastern cohort. Female sex, diabetes, reinfection, and hospitalization predicted delayed recovery. Persistent symptoms and impaired HRQoL highlight the need for early risk stratification and structured post-COVID care.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-11468-3.},
}
@article {pmid40884498,
year = {2026},
author = {Edwards, DL and Feldstein, LR and Dalton, AF and Ford, ND and Saydah, SH},
title = {Prevalence of Symptoms Associated With Long COVID Among Adolescents in the United States, Summer 2022.},
journal = {The Journal of infectious diseases},
volume = {233},
number = {2},
pages = {e352-e362},
doi = {10.1093/infdis/jiaf454},
pmid = {40884498},
issn = {1537-6613},
support = {/CC/CDC HHS/United States ; //Porter Novelli/ ; },
mesh = {Humans ; Adolescent ; *COVID-19/epidemiology/diagnosis ; Male ; Female ; United States/epidemiology ; Prevalence ; Child ; SARS-CoV-2/isolation &amp; purification ; Self Report ; Seasons ; },
abstract = {BACKGROUND: Limited information is known about long COVID among adolescents. This study compared the risks associated with symptoms among adolescents who tested positive, were tested but never tested positive, or who were never tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.<br><br>METHODS: Porter Novelli survey data were collected from adolescents (aged 12-17 years) from 31 May 31 through 6 July 2022. Respondents self-reported their SARS-CoV-2 test results and were classified accordingly by test status. Wald &#x3c7;2 tests were used to determine whether demographic factors and characteristics related to symptoms differed by test status. Multivariable logistic regression models were used to estimate the odds of reporting (1) symptoms lasting 4 weeks or longer and (2) symptoms lasting 3 or more months by test status and SARS-CoV-2 variant period.<br><br>RESULTS: Data were collected from 784 respondents: 264 (34%) tested positive, 291 (37%) never tested positive, and 229 (29%) were never tested for SARS-CoV-2 infection. At least 1 symptom lasting &#x2265;4 weeks was reported by 41% of the positive respondents, compared to 12% of negative respondents and 11% of never tested respondents (P < .05). The odds of reporting at least 1 symptom lasting &#x2265;4 weeks did not vary by SARS-CoV-2 variant period. Adolescents who tested positive had increased odds of any neurological symptom lasting &#x2265;3 months compared to negative adolescents.<br><br>CONCLUSIONS: Our results demonstrate that adolescents who tested positive for SARS-CoV-2 were more likely to report at least 1 symptom lasting for at least 4 weeks. However, most of these symptoms appeared to have resolved within 3 months.},
}
@article {pmid40884088,
year = {2025},
author = {Mak, WA and Wapperom, D and Redel, AL and Koeleman, JGM and Smit, PW and Lam-Tse, WK and van der Poll, T and Chen, HJ and den Dunnen, J and Braunstahl, GJ and Ong, DSY},
title = {Seasonal Coronavirus-Induced Immunological Imprinting and Previous Herpesvirus Infections in Patients With Long COVID.},
journal = {Journal of medical virology},
volume = {97},
number = {9},
pages = {e70582},
pmid = {40884088},
issn = {1096-9071},
support = {//The study was supported by the Franciscus Hospital, Rotterdam, the Netherlands./ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/immunology/virology/complications ; Antibodies, Viral/blood/immunology ; Middle Aged ; Immunoglobulin G/blood/immunology ; Immunoglobulin M/blood ; *SARS-CoV-2/immunology ; Adult ; Aged ; *Herpesviridae Infections/immunology/virology/complications ; Immunoglobulin A/blood ; Seasons ; Spike Glycoprotein, Coronavirus/immunology ; Herpesviridae/immunology ; },
abstract = {Long COVID (LC) is a post-acute infection syndrome affecting 5%-10% of individuals infected by SARS-CoV-2. Here, we aimed to study SARS-CoV-2 humoral immunity, immunological imprinting by endemic coronaviruses, and previous herpesvirus infections in LC. We included 47 LC patients and 41 controls who fully recovered from COVID-19. We assessed IgG, IgA, and IgM antibody levels against SARS-CoV-2, seasonal coronaviruses, and herpesviruses using ELISAs and Microblot-Array panels. Additionally, we performed PCR to detect viral RNA/DNA and evaluated anti-nuclear autoantibodies linked to systemic autoimmune conditions. LC patients showed significantly reduced levels of SARS-CoV-2 anti-spike IgG and IgA but increased levels of endemic coronaviruses OC43 and HKU1 anti-spike IgG, suggesting immunological imprinting potentially driven by these coronaviruses. Furthermore, LC patients had higher levels of SARS-CoV-2 anti-spike IgM compared to anti-Spike IgG, possibly indicating impaired class switching. Interestingly, cytomegalovirus (CMV) p65 IgG levels were lower in LC patients and negatively correlated with fatigue severity. This study highlights immunological imprinting by seasonal coronaviruses and impaired antibody class switching as potential causes of SARS-CoV-2 immune escape and persistence in LC patients. Furthermore, our findings suggest an inverse association between CMV p65 IgG and fatigue severity in LC.},
}
@article {pmid40883647,
year = {2025},
author = {Fayyad-Kazan, M},
title = {MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential.},
journal = {Inflammopharmacology},
volume = {33},
number = {9},
pages = {4895-4910},
pmid = {40883647},
issn = {1568-5608},
mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *COVID-19/genetics/therapy ; *Inflammation/genetics ; *SARS-CoV-2 ; Animals ; },
abstract = {Since the onset of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), elucidating the molecular regulators of viral pathogenesis and host response has been a critical international research objective. Among these, microRNAs (miRNAs), small non-coding RNAs, that modulate gene expression post-transcriptionally-have emerged as central orchestrators of host-virus interactions. This review exhaustively examines the roles of host-derived miRNAs in SARS-CoV-2 infection, including their roles in viral entry, replication, immune evasion, inflammation, and tissue injury. Dysregulation of certain miRNAs, such as miR-155, miR-146a, and miR-21, has been implicated in disease severity, comorbidities (such as diabetes, obesity), neurological complications, and pregnancy complications. In long COVID (PASC), chronic miRNA changes are linked to persistent inflammation, fibrosis, and cardiometabolic impairment. We emphasize current breakthroughs in miRNA research, including machine learning algorithms for miRNA-based disease stratification, CRISPR-engineered miRNA modulation, exosomal miRNA delivery platforms, and miRNA-adjuvanted vaccines. These advances highlight the potential of miRNAs as diagnostic biomarkers and therapeutic targets. Nevertheless, shortcomings persist in clinical validation, delivery optimization, and tissue-specific miRNA function elucidation. These gaps must be addressed to involve miRNAs in controlling current and future viral infections. This review consolidated differentially expressed miRNAs across disease stages, comorbidities, and clinical settings, providing a valuable resource for translational research and therapeutic innovation.},
}
@article {pmid40880174,
year = {2025},
author = {Ferreira, AMS and Ferreira, FELL and Alverga, CCF and Nascimento, JAD and de Carvalho, ALB and de Freitas, GRM and de Moraes, JAC and Rocha, IDS and Silva, LTD and Alves, BCPDS and de Oliveira, CR and Cardoso, JRA and Anacleto, RMM and Pernambuco, L},
title = {Symptoms and Risk Factors for Long COVID: A Cross-Sectional Study in Primary Care.},
journal = {Journal of medical virology},
volume = {97},
number = {9},
pages = {e70579},
pmid = {40880174},
issn = {1096-9071},
support = {//This study was funded by the Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior - Brasil (CAPES) (ROR identifier: 00x0ma614)./ ; },
mesh = {Humans ; Female ; Male ; Middle Aged ; Cross-Sectional Studies ; *COVID-19/epidemiology/complications/diagnosis ; Primary Health Care ; Risk Factors ; Adult ; Aged ; Retrospective Studies ; Brazil/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; Young Adult ; Aged, 80 and over ; Sex Factors ; },
abstract = {This study aimed to determine the occurrence and risk factors for persistent symptoms after mild to moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients who presented in primary care during the 2021 pandemic. A retrospective cross-sectional survey was conducted in six public family health care units in Joao Pessoa, Brazil. A questionnaire with a set of 18 validated clinical outcomes was used to assess prolonged symptoms beyond 3 months of duration in 226 adults who had confirmed SARS-CoV-2 infection. Binary logistic regression models were used to estimate adjusted odds ratios (aOR) and risk factors for Long COVID. A total of 16 outcomes were significantly associated with Long COVID. The largest aOR were estimated for short-term memory loss, anxiety, and loss of attention. The risk factors for Long COVID included ≥ 5 symptoms (15.82, 7.33-34.15, p < 0.0001), female sex (aOR: 1.91, 95% CI: 1.03-3.53, p = 0.032), age 40-49 years (3.45, 1.14-10.51, p = 0.029), and age 70+ years (4.0, 1.01-15.51, p = 0.045). Findings highlight a high frequency of persistent symptoms in adults who initially had non-severe SARS-CoV-2 infection, who are predominantly of working age, and who did not present multiple comorbidities. This study supports the need for assessing clinical outcomes and risk factors on Long COVID in primary care using routinely recorded clinical outcomes.},
}
@article {pmid40872911,
year = {2025},
author = {Zambrano-Sánchez, G and Rivadeneira, J and Manterola, C and Otzen, T and Fuenmayor-González, L},
title = {Immunization as Protection Against Long COVID in the Americas: A Scoping Review.},
journal = {Vaccines},
volume = {13},
number = {8},
pages = {},
pmid = {40872911},
issn = {2076-393X},
support = {Folio (85220114).//ANID + SUBVENCI&#xd3;N A INSTALACI&#xd3;N EN LA ACADEMIA CONVOCATORIA A&#xd1;O 2022/ ; },
abstract = {INTRODUCTION: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic's impact, there is a lack of evidence of its efficacy in preventing long COVID in the region.<br><br>METHODS: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables.<br><br>RESULTS: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies.<br><br>CONCLUSIONS: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes.},
}
@article {pmid40872813,
year = {2025},
author = {Muthiah, D and Vaddadi, K and Liu, L},
title = {Breathless Aftermath: Post-COVID-19 Pulmonary Fibrosis.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
pmid = {40872813},
issn = {1999-4915},
support = {P30 GM149368/GM/NIGMS NIH HHS/United States ; R01 HL157450/HL/NHLBI NIH HHS/United States ; R21 AI189861/AI/NIAID NIH HHS/United States ; R01HL157450, R21AI189861 and P30GM149368//National Institutes of Health grants, Oklahoma Center for Adult Stem Cell Research and the Lundberg-Kienlen Endowment fund (to LL)/ ; },
mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology ; SARS-CoV-2 ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {A significant number of individuals recovering from COVID-19 continue to experience persistent symptoms, collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or long COVID. Among these complications, post-COVID-19 pulmonary fibrosis (PC19-PF) is one of the most severe long-term outcomes, characterized by progressive lung scarring, chronic respiratory impairment, and reduced quality of life. Despite the increasing prevalence of PC19-PF, its underlying mechanisms remain poorly understood. In this review, we provide a comprehensive overview of PC19-PF, including its epidemiology, clinical manifestations, diagnostic strategies, and mechanistic insights. Additionally, we highlight the shared pathways between PC19-PF and other fibrotic lung diseases and discuss emerging therapeutic strategies. This review consolidates emerging insights from both clinical and experimental studies to advance our understanding of PC19-PF pathogenesis and guide the development of mechanism-based therapeutic approaches.},
}
@article {pmid40872762,
year = {2025},
author = {Cao, Y and Wang, Y and Huang, D and Tan, YJ},
title = {The Role of SARS-CoV-2 Nucleocapsid Protein in Host Inflammation.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
pmid = {40872762},
issn = {1999-4915},
support = {T2EP30121-0012//Ministry of Education/ ; },
mesh = {Humans ; *Coronavirus Nucleocapsid Proteins/immunology/metabolism ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology ; *Inflammation/immunology/virology ; *Phosphoproteins/immunology/metabolism ; Host-Pathogen Interactions ; Animals ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery-known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders.},
}
@article {pmid40869608,
year = {2025},
author = {Popa, MV and Gurzu, IL and Handra, CM and Mandanach, C and Gurzu, B and Mîndru, DE and Duceac Covrig, M and Ciuhodaru, MI and Duceac, LD},
title = {Long COVID in Healthcare Workers from a Pediatric Hospital in Romania: A Cross-Sectional Study of Prevalence, Symptom Burden, and the Role of Vaccination and Reinfection.},
journal = {Journal of clinical medicine},
volume = {14},
number = {16},
pages = {},
pmid = {40869608},
issn = {2077-0383},
abstract = {Background/Objectives: Long COVID, characterized by persistent symptoms following SARS-CoV-2 infection, poses a significant occupational health concern among healthcare workers (HCWs). This study aimed to evaluate the prevalence of long COVID, symptom patterns, work-related impact, and vaccination status among healthcare personnel in a Romanian pediatric hospital. Methods: A cross-sectional study was conducted in 2024 among 903 hospital employees during routine occupational health assessments. Data were collected using structured questionnaires and medical records, focusing on previous SARS-CoV-2 infection, vaccination status, persistent symptoms, and functional impact. Results: Long COVID was identified in 28.6% of participants, with excessive fatigue (53.5%), musculoskeletal pain, respiratory difficulties, and cognitive complaints being the most common symptoms. Staff with chronic comorbidities or increased exposure risk had significantly higher rates of functional impairment. Fewer reinfections were reported among vaccinated individuals; however, vaccination was not significantly associated with the presence of long COVID symptoms. Older age and comorbidities were correlated with higher risk. Conclusions: The findings underline the need for long-term occupational health strategies and individualized support programs for HCWs affected by long COVID, particularly in high-risk groups.},
}
@article {pmid40868989,
year = {2025},
author = {Cimmino, G and D'Elia, S and Morello, M and Titolo, G and Luisi, E and Solimene, A and Serpico, C and Conte, S and Natale, F and Loffredo, FS and Bianco, A and Golino, P},
title = {Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
pmid = {40868989},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/pathology ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology/pathology ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu-characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)-and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals.},
}
@article {pmid40868961,
year = {2025},
author = {Florea, CE and Bălaș-Maftei, B and Rotaru, A and Abudanii, PL and Vieru, ST and Grigoriu, M and Stoian, A and Manciuc, C},
title = {Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
pmid = {40868961},
issn = {2075-1729},
abstract = {Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body's immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver's central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection.},
}
@article {pmid40868937,
year = {2025},
author = {Troisi, M and Troisi, S and Vitiello, L and Strianese, D and Bellucci, C and Rinaldi, M and D'Andrea, L and Costagliola, C},
title = {Ocular and Neurological Sequelae in Long COVID: Dry Eye, Asthenopia, Sleep Disorders, Asthenia, and Restless Legs Syndrome-A Case Report with Literature Review.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
pmid = {40868937},
issn = {2075-1729},
abstract = {This case report presents a unique constellation of symptoms-including dry eye disease, visual and general asthenia, sleep disturbances, and restless legs syndrome-in a patient with a recent history of coronavirus disease 2019 (COVID-19) infection. While these symptoms have individually been associated with either COVID-19 or long COVID, their concurrent presentation and the simultaneous, positive response across all manifestations to a combined therapeutic regimen have not been previously described in a single case. The patient demonstrated notable improvement in both ocular and systemic symptoms following a six-week treatment with topical tear substitutes and oral administration of melatonin, and a multivitamin supplement including B-complex vitamins, antioxidants, and neuroprotective agents (Colinplus Delta[®], Farmaplus Italia Srl, Via Giovanni Porzio 4, 80143 Napoli, Italy). This response suggests a possible shared pathophysiological mechanism underlying these manifestations, potentially involving post-viral neuroinflammation, immune dysregulation, oxidative stress, or autonomic dysfunction. This case report highlights the need for an increased awareness of the interconnected nature of ocular and neurological symptoms in long COVID and supports further research into non-invasive, multimodal treatment strategies for this emerging clinical spectrum.},
}
@article {pmid40868144,
year = {2025},
author = {Haagsma, AB and Otto, FG and de Sá Vianna, MLG and Maingue, PM and Muller, AP and de Oliveira, NHDS and Abbott, LA and da Silva, FPG and Klein, CK and Herzog, DM and Fantin Unruh, JCB and Schoeler, L and Miyasaki, D and Soni, JF and Stival, RSM and Baena, CP},
title = {Clinical Evaluation of COVID-19 Survivors at a Public Multidisciplinary Health Clinic.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
pmid = {40868144},
issn = {2227-9059},
support = {3465//National Council for Scientific and Technological Development/ ; },
abstract = {Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53-196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03-1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset.},
}
@article {pmid40868058,
year = {2025},
author = {Gonzaga, A and Martinez-Navarrete, G and Macia, L and Anton-Bonete, M and Cahuana, G and Tejedo, JR and Zorrilla-Muñoz, V and Fernandez-Jover, E and Andreu, E and Eguizabal, C and Pérez-Martínez, A and Solano, C and Hernández-Blasco, LM and Soria, B},
title = {Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
pmid = {40868058},
issn = {2227-9059},
support = {ICI21/00016//Instituto de Salud Carlos III/ ; AVI-GVA-COVID19-068//Valencian Agency of Innovation(AVI)/ ; GVA-COVID19/2021-047//Valencian Agency of Innovation(AVI)/ ; NA//Al-Andalus Biopharma SL/ ; },
abstract = {Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC).},
}
@article {pmid40867811,
year = {2025},
author = {Villegas Sánchez, V and Chávez Pacheco, JL and Palacios Arreola, MI and Sierra-Vargas, MP and Colín Godinez, LA and Ahumada Topete, VH and Fernández Plata, R and Higuera-Iglesias, A and Lara-Lemus, R and Aquino-Gálvez, A and Torres-Espíndola, LM and Castillejos-López, M},
title = {A Systematic Review of Genetic Variants in Glutathione S-Transferase Genes and Their Dual Role in SARS-CoV-2 Pathogenesis: From Acute Respiratory Complications to Long COVID.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
pmid = {40867811},
issn = {2076-3921},
abstract = {Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID.},
}
@article {pmid40867133,
year = {2025},
author = {Tsaava, M and Basishvili, T and Sakhelashvili, I and Eliozishvili, M and Oniani, N and Lortkipanidze, N and Tarielashvili, M and Khoshtaria, L and Darchia, N},
title = {From Lockdowns to Long COVID-Unraveling the Link Between Sleep, Chronotype, and Long COVID Symptoms.},
journal = {Brain sciences},
volume = {15},
number = {8},
pages = {},
pmid = {40867133},
issn = {2076-3425},
abstract = {Background/Objectives: Given the heterogeneous nature of long COVID, its treatment and management remain challenging. This study aimed to investigate whether poor pre-pandemic sleep quality, its deterioration during the peak of the pandemic, and circadian preference increase the risk of long COVID symptoms. Methods: An online survey was conducted between 9 October and 12 December 2022, with 384 participants who had recovered from COVID-19 at least three months prior to data collection. Participants were categorized based on the presence of at least one long COVID symptom. Logistic regression models assessed associations between sleep-related variables and long COVID symptoms. Results: Participants with long COVID symptoms reported significantly poorer sleep quality, higher perceived stress, greater somatic and cognitive pre-sleep arousal, and elevated levels of post-traumatic stress symptoms, anxiety, depression, and aggression. Fatigue (39.8%) and memory problems (37.0%) were the most common long COVID symptoms. Sleep deterioration during the pandemic peak was reported by 34.6% of respondents. Pre-pandemic poor sleep quality, its deterioration during the pandemic, and poor sleep at the time of the survey were all significantly associated with long COVID. An extreme morning chronotype consistently predicted long COVID symptoms across all models, while an extreme evening chronotype was predictive only when accounting for sleep quality changes during the pandemic. COVID-19 frequency, severity, financial impact, and somatic pre-sleep arousal were significant predictors in all models. Conclusions: Poor sleep quality before the pandemic and its worsening during the pandemic peak are associated with a higher likelihood of long COVID symptoms. These findings underscore the need to monitor sleep health during pandemics and similar global events to help identify at-risk individuals and mitigate long-term health consequences, with important clinical and societal implications.},
}
@article {pmid40880119,
year = {2025},
author = {Bobato, GR and Rocha, JQ and Guizoni, DM and Nóbrega, NRC and Moura, LD and Rocha, ML and Velloso, LA and Carneiro, EM and Antunes-Correa, LM and Davel, AP},
title = {Extracellular vesicles from post-COVID-19 patients alter endothelial function under protein restriction.},
journal = {American journal of physiology. Cell physiology},
volume = {329},
number = {4},
pages = {C1121-C1129},
doi = {10.1152/ajpcell.00450.2025},
pmid = {40880119},
issn = {1522-1563},
mesh = {*COVID-19/metabolism/complications/physiopathology/pathology ; *Extracellular Vesicles/metabolism/pathology ; Animals ; Humans ; Male ; *Endothelium, Vascular/metabolism/physiopathology ; Mice ; Female ; *Diet, Protein-Restricted/adverse effects ; Vasodilation/drug effects ; *Endothelial Cells/metabolism ; Middle Aged ; Mice, Inbred C57BL ; Aged ; Aorta/metabolism ; SARS-CoV-2 ; },
abstract = {The COVID-19 pandemic worsened global food insecurity and malnutrition. Protein restriction increases the risk of poor COVID-19 outcomes and cardiovascular disease. Post-COVID-19 syndrome remains a public health concern, although its underlying mechanisms are not yet fully understood. Extracellular vesicles (EVs), released by most cell types in response to infections, have been implicated in endothelial dysfunction during the post-COVID phase. We hypothesized that EV contribute to endothelial cell (EC) dysfunction in long-term COVID-19, particularly in the setting of protein malnutrition. Circulating EVs were isolated from patients at 1 and 6 months (mo) after hospital discharge due to severe COVID-19. Endothelial relaxation was assessed in mouse aortas after a 3-mo normoprotein or low-protein diet (LP). LP feeding reduced endothelium-dependent relaxation to acetylcholine, but EVs from post-COVID patients (1 and 6 mo) restored endothelium-dependent relaxation. This EV effect was abolished by catalase, but not by l-NAME (a nitric oxide synthase inhibitor) or indomethacin (a cyclooxygenase inhibitor). Aortas from LP mice incubated with post-COVID EVs exhibited reduced catalase expression and increased 4-hydroxynonenal (4-HNE) adducts. In vitro amino acid restriction increased EC death (Hoechst/Pi), and reduced nitric oxide (Diaminofluorescein-FM diacetato) and H2O2 (Amplex red) levels. Incubation with post-COVID EVs for 24 h increased H2O2 only in amino acid-restricted EC. EVs had no significant effect on acetylcholine-induced relaxation in normoprotein-fed mice or on EC parameters in vitro under control conditions. These findings suggest that EVs from patients 1 and 6 mo after severe COVID-19 impact aortic endothelial function by increasing H2O2 contribution under conditions of malnutrition.NEW &amp; NOTEWORTHY Our study demonstrated that circulating extracellular vesicles (EVs) from patients 1 and 6 mo after severe COVID-19 altered endothelial function under protein restriction but not in healthy vessels. Post-COVID EVs enhanced the contribution of H2O2 to endothelium-dependent relaxation, associated with reduced catalase and increased 4-HNE-modified protein expression. These findings identified EVs from long COVID patients as potential mediators of endothelial dysfunction particularly under malnutrition-related conditions.},
}
@article {pmid40879554,
year = {2026},
author = {Herlitz, J and Pohl, A and Gerlach, AL},
title = {Googling as avoidance: anxiety responses to online health information about long COVID.},
journal = {Anxiety, stress, and coping},
volume = {39},
number = {2},
pages = {248-262},
doi = {10.1080/10615806.2025.2551018},
pmid = {40879554},
issn = {1477-2205},
mesh = {Humans ; *COVID-19/psychology ; Male ; Female ; *Anxiety/psychology ; Adult ; Heart Rate/physiology ; *Internet ; Galvanic Skin Response/physiology ; Young Adult ; *Avoidance Learning ; *Consumer Health Information/methods ; Self Report ; Respiratory Rate/physiology ; Middle Aged ; },
abstract = {Background and Objectives:People search the internet for health information, although this increases anxiety and worry, particularly in the health-anxious. Applying the avoidance theory of worrying, we tested whether online health research serves to emotionally distance oneself from illness.Design and Method: Googling long COVID was compared to imagery of suffering from the disease in 60 participants. We assumed that anxiety responses to googling would be lower than during imagery, but higher than during baseline. Self-report, skin conductance (SCL), heart rate (HR), heart rate variability (HRV), and respiration rate (RR) indicated anxiety.Results: SCL was higher during imagery than googling. However, HR, high frequency HRV and RR signaled stronger activation by googling than imagery. Physiological measures demonstrated a stronger anxiety response to googling compared to baseline. Regarding self-report, an interaction effect of sequence and condition emerged. Those who started with googling reported higher levels of anxiety during imagery. Among participants who began with imagery, anxiety was elevated during googling compared to baseline, but there were no significant differences when compared to anxiety during imagery.Conclusions: Results at least partially support the notion that health-related internet research may serve to avoid the physical and self-reported anxiety responses.},
}
@article {pmid40876395,
year = {2025},
author = {Ayuso García, B and Pérez López, A and Besteiro Balado, Y and Romay Lema, E and Marchán-López, &#xc1; and Rabuñal Rey, R},
title = {Prevalence of symptoms and quality of life 3 years after COVID-19: Long term follow-up using the C19-YRS questionnaire in a Spanish hospital.},
journal = {Medicina clinica},
volume = {165},
number = {5},
pages = {107138},
doi = {10.1016/j.medcli.2025.107138},
pmid = {40876395},
issn = {1578-8989},
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; *Quality of Life ; Male ; Female ; Spain/epidemiology ; Prospective Studies ; Aged ; Follow-Up Studies ; Prevalence ; Middle Aged ; Surveys and Questionnaires ; Aged, 80 and over ; Anxiety/epidemiology/etiology ; Fatigue/epidemiology/etiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Dyspnea/epidemiology/etiology ; Time Factors ; },
abstract = {INTRODUCTION: Post-COVID syndrome can hinder the quality of life of patients. This study aims at describing this syndrome and its natural history.<br><br>METHODS: Prospective study including 443 inpatient and outpatient survivors of COVID-19 acquired between March and May 2020. Patients with dementia, nursing home residents, and those rejecting participation were excluded. Symptoms were assessed 10 and 36 months after the infection using the C19-YRS questionnaire. The prevalence and severity of symptoms, as well as risk factors for symptom persistence were investigated.<br><br>RESULTS: At 10 months 62.3% of patients reported at least one symptom, down to 54.9% at 36 months. Fatigue (37.2%), dyspnea at exertion (33.4%), and anxiety (33.4%) were the most prevalent symptoms, all of which showed improvement at follow up. Domain-specific impairment was the strongest risk factor for symptom persistence. Most patients reported a similar health status (69.4%) and quality of life (71.4%) compared with their pre-infection condition.<br><br>CONCLUSIONS: Although frequent, post-COVID-19 symptoms improve over time, while quality of life remains stable compared to patients baseline status.},
}
@article {pmid40876137,
year = {2025},
author = {Hotez, PJ},
title = {COVID-19 vaccinations in America: Don't forget long COVID and the post-acute sequelae.},
journal = {Vaccine},
volume = {63},
number = {},
pages = {127676},
doi = {10.1016/j.vaccine.2025.127676},
pmid = {40876137},
issn = {1873-2518},
}
@article {pmid40859683,
year = {2025},
author = {Gao, Y and Duan, C and Miao, T and Shen, Q and Yu, J and Shen, S and Chen, Y and Shen, Y and Zhang, K},
title = {Association between depression and three key COVID-19-related outcomes: The SHARE study.},
journal = {Human vaccines &amp; immunotherapeutics},
volume = {21},
number = {1},
pages = {2551930},
pmid = {40859683},
issn = {2164-554X},
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Middle Aged ; Male ; Female ; Aged ; *Depression/epidemiology/complications ; Europe/epidemiology ; *COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2 ; Vaccination/statistics &amp; numerical data ; Risk Factors ; },
abstract = {This study investigated the potential associations between preexisting depression and COVID-19 vaccination, SARS-CoV-2 infection risk, and long COVID among middle-aged and older Europeans, based on the Survey of Health, Ageing and Retirement in Europe (SHARE). A total of 31,115 participants were included to assess the relationship between depression and COVID-19 vaccination 11,146 to evaluate depression-related SARS-CoV-2 infection risk, and 11,142 to study the impact of depression on the occurrence of long COVID. Multivariable logistic model was performed and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Compared to non-depressed individuals, those with depression were 0.72 times less likely to receive the COVID-19 vaccine (95% CI: 0.67-0.77), had a 1.15 times higher risk of SARS-CoV-2 infection (95% CI: 1.02-1.30), and were 1.21 times more likely to develop long COVID (95% CI: 1.05-1.38), with these associations strengthening as the severity of depression increased. Preexisting depression might be linked to reduced COVID-19 vaccination odds and an elevated risk of SARS-CoV-2 infection and long COVID, although further high-quality prospective studies with larger samples are needed to confirm the findings.},
}
@article {pmid40875678,
year = {2025},
author = {Schapowal, A},
title = {[Long COVID, Post-COVID-Syndrom: Langzeitfolgen von SARS-CoV-2-Infektionen und Nutzen von standardisierten Ginkgo-biloba Extrakten].},
journal = {Complementary medicine research},
volume = {32},
number = {5},
pages = {432-437},
doi = {10.1159/000548075},
pmid = {40875678},
issn = {2504-2106},
mesh = {Humans ; *Ginkgo biloba/chemistry ; *Plant Extracts/therapeutic use ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Phytotherapy ; Ginkgo Extract ; },
abstract = {Hintergrund: Long COVID und das Post-COVID-Syndrom sind langfristige Folgen einer SARS-CoV-2-Infektion, die eine Vielzahl physischer, kognitiver und psychischer Symptome hervorrufen können. Dazu gehören Erschöpfung, Atemnot, Gedächtnisstörungen und Schlafprobleme. Die zugrunde liegenden Mechanismen sind noch nicht vollständig geklärt, umfassen jedoch persistierende Viruspartikel, mikrovaskuläre Dysfunktionen, Autoimmunreaktionen und eine Dysregulation des autonomen Nervensystems. Fragestellung: Welchen Nutzen könnten standardisierte Ginkgo-biloba-Extrakte aufgrund ihrer pharmakologischen Wirkungen und ihrer klinischen Wirksamkeit bei Long COVID und Post-COVID-Syndrom bringen? Zusammenfassung: Die Diagnose von Long COVID bleibt aufgrund fehlender standardisierter Tests eine Herausforderung. Therapeutisch wird ein multimodaler Ansatz empfohlen, der symptomatische Medikation, Physiotherapie, Psychotherapie sowie Ernährungs- und Bewegungstherapie umfasst. Ein vielversprechender ergänzender Therapieansatz ist die Verwendung von standardisierten Ginkgo-biloba-Extrakten. Dank ihrer antioxidativen, entzündungshemmenden und neuroprotektiven Eigenschaften könnten sie zur Verbesserung kognitiver Beeinträchtigungen, Fatigue und kardiovaskulärer Symptome beitragen. Erste Studien und Fallberichte deuten auf positive Effekte hin, jedoch sind weitere klinische Untersuchungen erforderlich, um die Wirksamkeit zu bestätigen. Kernaussagen: Long COVID und das Post-COVID-Syndrom betreffen zahlreiche Organsysteme und beeinträchtigen die Lebensqualität erheblich. Die Diagnose bleibt schwierig, da es keine spezifischen Tests gibt. Eine multimodale Therapie ist derzeit der vielversprechendste Behandlungsansatz. Standardisierte Ginkgo-biloba-Extrakte zeigen in ersten Studien positive Effekte auf neurokognitive und kardiovaskuläre Symptome.},
}
@article {pmid40875136,
year = {2025},
author = {Sala, MA and Koralnik, IJ},
title = {Five years later: no short answers for Long COVID.},
journal = {GeroScience},
volume = {47},
number = {5},
pages = {6203-6206},
pmid = {40875136},
issn = {2509-2723},
}
@article {pmid40873616,
year = {2025},
author = {Goulart, CDL and Maldaner, V and Alves, CCA and Milani, M and Milani, J and Gonçalves da Costa, AC and Alves, ML and Borges, RF and Sobral, CCCH and Moraes, LA and Coutinho, JC and Gomes, NO and Tolfo Franzoni, L and Ferrari, F and Borghi-Silva, A and Cahalin, LP and Cipriano, GFB and Cipriano Junior, G and Stein, R},
title = {Recovery from COVID-19: a 12-month follow-up study on cardiorespiratory fitness and pulmonary function.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1638317},
pmid = {40873616},
issn = {2297-055X},
abstract = {INTRODUCTION AND AIM: Long COVID, characterized by persistent symptoms after acute infection, poses a major public health challenge. Understanding its long-term effects is crucial, particularly in relation to cardiorespiratory recovery. This study aimed to assess changes in cardiorespiratory fitness (CRF) and pulmonary function (PF) over 12 months following acute COVID-19, addressing a significant gap in current knowledge about the disease's lasting impact.<br><br>METHODS: This prospective cohort study included 29 individuals previously diagnosed with post-acute COVID-19. The baseline data were collected during the acute phase of infection. Participants underwent clinical evaluation, cardiopulmonary exercise testing (CPET), spirometry, and maximal inspiratory pressure (MIP) measurement at baseline and again after 12 months.<br><br>RESULTS: After one-year, significant improvements were observed across several CPET parameters, including VE/MVV ratio (Cohen's D&#x2009;=&#x2009;0.66), peak oxygen uptake (VO2peak) in both absolute and relative terms (ml/min: d&#x2009;=&#x2009;0.67; and ml/kg/min: d&#x2009;=&#x2009;0.45), oxygen uptake efficiency slope (OUES; D&#x2009;=&#x2009;0.47) and a reduction in VE/VCO2 slope (D&#x2009;=&#x2009;0.80). Pulmonary function improved with increases in % predicted forced expiratory volume in 1&#x2005;s (FEV1; d&#x2009;=&#x2009;0.67) and forced vital capacity (FVC; D&#x2009;=&#x2009;0.67). MIP improved significantly (D&#x2009;=&#x2009;0.67), and the prevalence of inspiratory muscle weakness decreased from 20.7% at baseline to 3.5% at follow-up.<br><br>CONCLUSION: Despite the severity of their initial illness, patients demonstrated substantial recovery in CRF, PF, and inspiratory muscle strength over 12 months.},
}
@article {pmid40869200,
year = {2025},
author = {Lesgards, JF and Cerdan, D and Perronne, C},
title = {Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
pmid = {40869200},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/prevention &amp; control/physiopathology ; *COVID-19 Vaccines/adverse effects/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin-angiotensin-aldosterone system (RAAS), the kininogen-kinin-kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects.},
}
@article {pmid40866305,
year = {2025},
author = {Bombardieri, AM and Denoue, CF},
title = {Cervical sympathetic block to treat Long COVID: a scoping review.},
journal = {Regional anesthesia and pain medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/rapm-2025-106879},
pmid = {40866305},
issn = {1532-8651},
abstract = {BACKGROUND: Long COVID is a complex and poorly understood condition characterized by persistent symptoms such as autonomic dysfunction, fatigue, neurocognitive impairment, and olfactory disturbances. Current treatments offer limited and inconsistent benefits. Dysregulation of the sympathetic nervous system is increasingly recognized as a contributor to Long COVID pathophysiology. Cervical sympathetic block (CSB), a procedure that modulates sympathetic tone, has emerged as a potential therapeutic approach.<br><br>OBJECTIVE: To review the existing literature on CSB, for Long COVID, focusing on symptom outcomes, proposed mechanisms, and procedural considerations.<br><br>EVIDENCE REVIEW: A structured literature search across PubMed, Embase, Scopus, and Web of Science identified studies published between 2022 and March 2025 reporting on CSB in adults with Long COVID. Eligible articles included case reports, case series, observational studies, and one randomized controlled trial evaluating symptom outcomes after the procedure.<br><br>FINDINGS: Sixteen studies involving 224 patients were included. Most reported improvement in fatigue, brain fog, and autonomic symptoms, including reduced heart rate and enhanced orthostatic tolerance. Cognitive and psychiatric symptoms such as memory impairment, anxiety, and depression showed variable improvement. Olfactory recovery was inconsistent and appeared to depend on symptom severity. Symptom relief was observed after both unilateral and bilateral blocks, with some responses lasting up to 1 year. No serious complications were reported.<br><br>CONCLUSIONS: CSB may offer symptom relief in Long COVID, particularly for fatigue, brain fog, and dysautonomia. However, the evidence remains preliminary and limited by small sample sizes and methodological heterogeneity. Controlled trials are needed to establish efficacy and patient selection criteria.},
}
@article {pmid40865177,
year = {2025},
author = {De Miguel-Escribano, M and Martín-Garrido, I and Garrido-Montes, M and Pertusa-Mataix, R and Corchero-Gijón, J and Morillo, JSG},
title = {Brain hypometabolism and cognitive impairment in long COVID: Insights from [18F]FDG-PET-CT imaging and neurocognitive assessment.},
journal = {Medicina clinica},
volume = {165},
number = {5},
pages = {107140},
doi = {10.1016/j.medcli.2025.107140},
pmid = {40865177},
issn = {1578-8989},
mesh = {Humans ; *Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Male ; *COVID-19/complications/metabolism/psychology/diagnostic imaging ; Female ; *Cognitive Dysfunction/etiology/diagnostic imaging/metabolism ; Middle Aged ; Radiopharmaceuticals ; Aged ; *Brain/metabolism/diagnostic imaging ; Neuropsychological Tests ; Adult ; },
abstract = {INTRODUCTION: Despite the progressive socioeconomic and healthcare recovery following the SARS-CoV-2 pandemic, its sequelae remain markedly evident today. Among them, Long COVID significantly impairs patient functionality and quality of life. Neurocognitive impairment stands out as one of its most debilitating manifestations.<br><br>PATIENTS AND METHODS: We assessed 16 patients diagnosed with Long COVID and neurocognitive dysfunction, quantifying the degree of impairment using cognitive evaluation tests and comparing these results with findings from prior [18F]FDG-PET-CT brain scans.<br><br>RESULTS: The mean cognitive test scores demonstrated significant impairment. Patients predominantly exhibited mild hypometabolism across various regions, with the cerebellum identified as the most frequently affected area. Those with more pronounced [18F]FDG-PET-CT abnormalities exhibited greater cognitive deficits. Greater hypometabolism and thalamic involvement were associated with lower cognitive assessment score.<br><br>CONCLUSION: We support the role of cerebral hypometabolism in the development of neurocognitive impairment associated with Long COVID, although its underlying pathophysiological mechanisms remain to be elucidated. We further endorse the potential link between cerebellar hypometabolism and cognitive decline. Greater severity in brain [18F]FDG-PET-CT abnormalities and thalamic dysfunction may correlate worse cognitive impairment.},
}
@article {pmid40863252,
year = {2025},
author = {Srikanth, S and Boulos, JR and Ivankovic, D and Gonzales, L and Dean, D and Boccuto, L},
title = {Long COVID-19: A Concept Analysis.},
journal = {Infectious disease reports},
volume = {17},
number = {4},
pages = {},
pmid = {40863252},
issn = {2036-7430},
support = {P20 GM121342/GM/NIGMS NIH HHS/United States ; },
abstract = {Background/Objectives: In late 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic called the 'coronavirus disease 2019' (COVID-19). After the acute SARS-CoV-2 infection, many individuals (up to 33%) complained of unexplained symptoms involving multiple organ systems and were diagnosed as having Long COVID-19 (LC-19). Currently, LC-19 is inadequately defined, requiring the formation of consistent diagnostic parameters to provide a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy. LC-19 represents a significant burden on multiple levels. The reduced ability of workers to return to work or compromised work efficiency has led to consequences at national, economic, and societal levels by increasing dependence on community services. On a personal scale, the isolation and helplessness caused by the disease and its subsequent impact on the patient's mental health and quality of life are incalculable. Methods: In this paper, we used Walker and Avants' eight-step approach to perform a concept analysis of the term "Long COVID-19" and define its impact across these parameters. Results: Using this methodology, we provide an improved definition of LC-19 by connecting the clinical symptomology with previously under-addressed factors, such as mental, psychological, economic, and social effects. This definition of LC-19 features can help improve diagnostic procedures and help plan relevant healthcare services. Conclusions: LC-19 represents a complex and pressing public health challenge with diverse symptomology, an unpredictable timeline, and complex pathophysiology. This concept analysis serves as a tool for improving LC-19 definition, but it remains a dynamic disease with evolving diagnostic and therapeutic approaches, requiring deeper investigation and understanding of its long-term effects.},
}
@article {pmid40863220,
year = {2025},
author = {Ramamoorthy, R and Speciale, AR and West, EM and Hussain, H and Elumalai, N and Schmitz Abe, KE and Ramesh, MC and Agrawal, PB and Jayakumar, AR and Paidas, MJ},
title = {Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {8},
pages = {},
pmid = {40863220},
issn = {2079-9721},
support = {Department of Obstetrics, Gynecology, and Reproductive Sciences//University of Miami Miller School of Medicine/ ; Team Science Award//University of Miami Miller School of Medicine/ ; Charles M. Vallee Foundation//University of Miami Miller School of Medicine/ ; Muriel, Murrary &amp; Robert Smith Foundation COVID-19 Research Fund//University of Miami Miller School of Medicine/ ; },
abstract = {BACKGROUND: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK).<br><br>METHODS: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR.<br><br>RESULTS: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice.<br><br>CONCLUSIONS: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae.},
}
@article {pmid40859262,
year = {2025},
author = {Ballhausen-Lübcker, S and Ruß, AK and Lieb, W and Schäfer, A and Krist, L and Fricke, J and Scheibenbogen, C and Rabe, KF and Maetzler, W and Maetzler, C and Laudien, M and Frank, D and Heyckendorf, J and Miljukov, O and Haeusler, KG and El Mokhtari, NE and Witzenrath, M and Vehreschild, JJ and Appel, KS and Chaplinskaya-Sobol, I and Tamminga, T and Nürnberger, C and Schmidbauer, L and Morbach, C and Störk, S and Reese, JP and Keil, T and Heuschmann, P and Schreiber, S and Krawczak, M and Bahmer, T},
title = {Subdomains of Post-COVID Syndrome (PCS) - a population-based study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1072},
pmid = {40859262},
issn = {1471-2334},
mesh = {Humans ; *COVID-19/complications/epidemiology/psychology ; Male ; Female ; Middle Aged ; Adult ; Severity of Illness Index ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Aged ; Fatigue ; Cohort Studies ; Resilience, Psychological ; },
abstract = {PURPOSE: 'Post-COVID Syndrome' (PCS), which encompasses the multifaceted sequelae of COVID-19, can be severity-graded by a previously defined score encompassing 12 different long-term symptom complexes. The PCS score was shown to have two main predictors, namely acute COVID-19 severity and individual resilience. The purpose of the present study was to verify these predictors and to assess their detailed relationship to the symptom complexes constituting the PCS score.<br><br>METHODS: The study drew upon a largely expanded dataset (n&#x2009;=&#x2009;3,372) from COVIDOM, the cohort study underlying the original PCS score definition. Classification and Regression Tree (CART) analysis served to resolve the detailed relationship between the predictors and the constituting symptom complexes of the PCS score.<br><br>RESULTS: Among newly recruited COVIDOM participants (n&#x2009;=&#x2009;1,930), the PCS score was again found to be associated with both its putative predictors. Of the score-constituting symptom complexes, neurological symptoms, sleep disturbance, and fatigue were predicted by individual resilience whereas the acute disease severity predicted exercise intolerance, chemosensory deficits, joint or muscle pain, signs of infection, and fatigue. These associations inspired the definition of two novel PCS scores that included the above-mentioned subsets of symptom complexes only. Similar to the original PCS score, both novel scores were found to be inversely correlated with quality of life as measured by the EQ-5D-5L index.<br><br>CONCLUSION: The two newly defined PCS scores may enable a more refined assessment of PCS severity, both in a research context and to delineate distinct PCS subdomains with possibly different therapeutic and interventional needs in clinical practise.},
}
@article {pmid40864005,
year = {2025},
author = {Bryarly, M and Robbins, NM and Roberts, M and Cabrera, J and Parsonnet, J and Martin, C and Hernandez, RS and Barshikar, S and Vernino, S},
title = {Minimal Objective Autonomic Dysfunction in Long COVID.},
journal = {Journal of the American College of Cardiology},
volume = {86},
number = {21},
pages = {2068-2070},
doi = {10.1016/j.jacc.2025.04.038},
pmid = {40864005},
issn = {1558-3597},
}
@article {pmid40861640,
year = {2025},
author = {Chiang, MC and Satko, KM and Shin, C and Sperry, BP and Cabral, ML and Crockett, Z and Gao, R and Yong, RJ and Ang, SP and Burns, SL and Kim, AJ},
title = {Stellate Ganglion Block for the Management of Long COVID Symptoms: A Retrospective Cohort Study.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88680},
pmid = {40861640},
issn = {2168-8184},
abstract = {Introduction The efficacy of stellate ganglion block (SGB) for managing post-acute sequelae of SARS-CoV-2 (PASC) remains an area of active exploration. In this study, we performed a retrospective analysis of PASC symptom improvements following SGB. Methods We performed a retrospective, survey-based cohort study at a single institution of patients with a history of PASC who underwent SGB at one of three different sites within Boston, MA, USA, between September 2022 and September 2024. The intervention was outpatient, office-based, with one or more unilateral SGBs. Results Fifty-two patients were included in the analysis. On average, patients underwent three SGB injections. Most patients reported improvement in PASC symptoms after SGB treatment. The most commonly reported symptoms that showed improvement were brain fog, fatigue, dizziness, and headache. A quarter of patients reported experiencing at least one adverse effect that was mostly short-lived. Conclusion SGB reduced the severity of many PASC symptoms, although there was high variability in the duration of symptom improvement. Further high-quality randomized clinical trials are warranted to investigate SGBs for the effective treatment of PASC.},
}
@article {pmid40861631,
year = {2025},
author = {Lee, KD},
title = {Multidisciplinary Management for Anterior Cutaneous Nerve Entrapment Syndrome (ACNES): A Case Series Including a Long COVID-19 Patient.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88703},
pmid = {40861631},
issn = {2168-8184},
abstract = {Anterior cutaneous nerve entrapment syndrome (ACNES) is an underrecognized cause of chronic abdominal wall pain. While nerve block injections are typically used as conservative treatment, persistent or recurrent cases may require surgical neurectomy. This case series presents five patients, including a long COVID-19 case, who underwent surgical treatment for ACNES at our institution. We integrated clinical presentation, CT imaging, surgical findings, rehabilitation strategies, and histopathological analysis to explore a multidisciplinary treatment approach. Preoperative CT was helpful in detecting muscle atrophy or nerve visualization, which guided rehabilitation and surgical planning. Histopathology revealed chronic compressive neuropathy in all cases, even among those with mild symptoms, suggesting that pain severity alone should not dictate surgical indications. Rehabilitation was effective in reducing muscle contraction and localizing symptoms, contributing to postoperative success and recurrence prevention. Our findings support the importance of individualized, proactive management that combines imaging, surgery, and rehabilitation, and highlight the potential for COVID-19-related neuropathy to contribute to ACNES.},
}
@article {pmid40858480,
year = {2025},
author = {Crosskey, M and McIntee, T and Preiss, S and Brannock, D and Baratta, JM and Yoo, YJ and Hadley, E and Blanceró, F and Chew, R and Loomba, J and Bhatia, A and Chute, CG and Haendel, M and Moffitt, R and Pfaff, ER and , },
title = {Re-engineering a machine learning phenotype to adapt to the changing COVID-19 landscape: a machine learning modelling study from the N3C and RECOVER consortia.},
journal = {The Lancet. Digital health},
volume = {7},
number = {8},
pages = {100887},
pmid = {40858480},
issn = {2589-7500},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Machine Learning ; *COVID-19/epidemiology/diagnosis ; Alanine/analogs &amp; derivatives/therapeutic use ; Male ; Adult ; Middle Aged ; Female ; SARS-CoV-2 ; United States/epidemiology ; Adenosine Monophosphate/analogs &amp; derivatives/therapeutic use ; },
abstract = {BACKGROUND: In 2021, we used the National COVID Cohort Collaborative (N3C) as part of the National Institutes of Health RECOVER Initiative to develop a machine learning pipeline to identify patients with a high probability of having post-acute sequelae of SARS-CoV-2 infection or long COVID. However, the increased home testing, missing documentation, and reinfections that characterise the pandemic beyond 2022 necessitated the re-engineering of our original model to account for these changes in the COVID-19 research landscape.<br><br>METHODS: Trained on 72&#x2009;745 patient records (36&#x2009;238 with long COVID and 36&#x2009;507 with no evidence of long COVID), our updated XGBoost model gathered data for each patient in overlapping 100-day periods that progressed through time and issued a probability of long COVID for each 100-day period. We ran the model on patients in N3C (n=5&#x2009;875&#x2009;065) who met at least one of the following criteria from Jan 1, 2020, to June 22, 2023: a U07&#xb7;1 (COVID-19) diagnosis code; a positive SARS-CoV-2 test; a U09&#xb7;9 (post-acute sequelae of SARS-CoV-2 infection) diagnosis code; a prescription for nirmatrelvir-ritonavir or remdesivir; or an M35&#xb7;81 (multisystem inflammatory syndrome in children [MIS-C]) diagnosis code. Each patient was given a model score that predicted long COVID status for each 100-day window in which they were aged &#x2265;18 years. If a patient had known acute COVID-19 during any 100-day window (including reinfections), we censored the data from 7 days before the diagnosis or positive test date to 28 days after. We ran the model on controls selected from pre-2020 data to assess the likelihood of false positives.<br><br>FINDINGS: The updated model had an area under the receiver operating characteristic curve of 0&#xb7;90. Precision and recall could be adjusted according to a given use case, depending on whether greater sensitivity or specificity was warranted. Using our model, we estimate the overall prevalence of long COVID among the COVID-19 positive cohort within N3C repository to be 10.4%.<br><br>INTERPRETATION: By eschewing the COVID-19 index date as an anchor point for analysis, we can assess the probability of long COVID among patients who might have tested at home, or with suspected (but untested) cases of COVID-19, or multiple SARS-CoV-2 reinfections. We view this exercise as a model for maintaining and updating any machine learning pipeline used for clinical research and operations.<br><br>FUNDING: National Institutes of Health RECOVER Initiative.},
}
@article {pmid40857408,
year = {2025},
author = {Bayarri-Olmos, R and Bain, W and Iwasaki, A},
title = {The role of complement in long COVID pathogenesis.},
journal = {JCI insight},
volume = {10},
number = {16},
pages = {},
pmid = {40857408},
issn = {2379-3708},
mesh = {Humans ; *COVID-19/immunology/complications ; *Complement System Proteins/immunology ; SARS-CoV-2/immunology ; Immunity, Innate/immunology ; Inflammation/immunology ; Complement Activation ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a debilitating condition that can develop after a SARS-CoV-2 infection and is characterized by a wide range of chronic symptoms, including weakness, neurocognitive impairment, malaise, fatigue, and many others, that affect multiple organ systems. At least 10% of individuals with a previous infection may develop long COVID, which affects their ability to perform daily functions and work. Despite its severity and widespread impact, this multisystemic condition remains poorly understood. Recent studies suggest that dysregulation of the complement system, a key component of the innate immune response, may contribute to the pathogenesis of long COVID, particularly in connection with coagulation, inflammation, and vascular injury. In this Review, we examine the evidence linking complement system dysregulation to long COVID and explore its potential role in driving disease pathology.},
}
@article {pmid40843696,
year = {2025},
author = {Rudroff, T},
title = {Theoretical Framework and Methodological Approach for Investigating Potential Associations Between Long COVID and Autism Spectrum Disorder Prevalence.},
journal = {NeuroSci},
volume = {6},
number = {3},
pages = {},
pmid = {40843696},
issn = {2673-4087},
abstract = {This perspective paper proposes a theoretical framework for investigating potential associations between Long COVID and rising autism spectrum disorder (ASD) prevalence through established epidemiological methodologies. I propose examining temporal correlations, biological mechanisms, and rigorous methodological approaches, including Mendelian randomization, animal models, and evidence-based analyses, that could distinguish association from causation. The proposed framework recognizes autism as neurodiversity while suggesting investigation of environmental factors that may influence expression of genetic predispositions. Hypothesized key mechanisms include neuroinflammation, cytokine alterations, and immune dysfunction. I emphasize the critical distinction between demonstrating statistical associations and establishing causal influence, proposing specific experimental designs that could test causality. This paper presents conceptual frameworks requiring future empirical validation and does not include original data analysis.},
}
@article {pmid40852766,
year = {2025},
author = {Ling, J and Li, J},
title = {What could cause the reactivation of Epstein-Barr virus in individuals with long COVID.},
journal = {Emerging microbes &amp; infections},
volume = {14},
number = {1},
pages = {2552712},
pmid = {40852766},
issn = {2222-1751},
}
@article {pmid40848989,
year = {2025},
author = {Liu, B and Song, S and Liu, W and Hu, Y and Wei, C and Zhou, L and Sun, Q and Tian, W and Chu, RYK and Wong, ICK and Hung, IFN and Wan, EYF and Li, X and Chui, CSL and Chan, EWY and Wong, CKH and Lai, FTT},
title = {Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study.},
journal = {The Journal of infection},
volume = {91},
number = {3},
pages = {106597},
doi = {10.1016/j.jinf.2025.106597},
pmid = {40848989},
issn = {1532-2742},
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Male ; Female ; Middle Aged ; Incidence ; Aged ; *Multimorbidity ; Hong Kong/epidemiology ; Retrospective Studies ; *Vaccination/statistics &amp; numerical data ; Adult ; *COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2 ; Aged, 80 and over ; Cohort Studies ; Chronic Disease/epidemiology ; },
abstract = {BACKGROUND: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination.<br><br>METHODS: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (&#x2265;3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list.<br><br>RESULTS: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96-313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18-69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85-88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27-74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23-1.29) for unvaccinated and 1.08 (95% CI: 1.05-1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups.<br><br>INTERPRETATION: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.},
}
@article {pmid40848897,
year = {2025},
author = {Vidal, KS and Cavendish, BA and Goerigk, S and Pita Batista, M and Oliveira Lima, AR and Pinto, BS and Neto Domingos, AA and de Sousa, JP and Pelosof, R and Bertola, L and Silva, V and Suemoto, CK and Razza, LB and Bikson, M and Pilloni, G and Charvet, L and Silva, PHR and Brunoni, AR},
title = {Transcranial direct current stimulation plus cognitive training for cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection: A randomized, double-blind, sham-controlled trial.},
journal = {Brain stimulation},
volume = {18},
number = {5},
pages = {1608-1616},
doi = {10.1016/j.brs.2025.08.018},
pmid = {40848897},
issn = {1876-4754},
mesh = {Humans ; *Transcranial Direct Current Stimulation/methods ; Double-Blind Method ; Female ; Male ; Middle Aged ; *COVID-19/complications/psychology/therapy ; Adult ; Aged ; Young Adult ; Adolescent ; *Cognitive Behavioral Therapy/methods ; Neuropsychological Tests ; *Cognitive Dysfunction/therapy/etiology ; Anxiety/therapy/etiology ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; Cognitive Training ; },
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) is characterized by persistent cognitive deficits alongside anxiety and depression symptoms that adversely affect quality of life. Cognitive training (CT) programs and non-invasive neuromodulation, specifically transcranial direct current stimulation (tDCS), have each shown promise for alleviating similar deficits in non-clinical populations. However, their combined efficacy has not yet been evaluated in PASC patients. Therefore, this study aimed to determine whether the combination of CT and tDCS produces benefits for cognitive and mood-related symptoms in individuals with PASC.<br><br>METHODS: We conducted a double-blind, randomized, sham-controlled clinical trial in adults aged 18-75 with confirmed SARS-CoV-2 infection within the past six months and persisting cognitive complaints. They were randomized to a 4-week in-person intervention of 20 weekday sessions of either active (2&#xa0;mA anodal-left, cathodal-right prefrontal stimulation) or sham tDCS paired with an app-based CT program. Primary outcomes were six standardized neuropsychological tests assessing verbal memory, working memory, executive functioning, attention, and language, administered at baseline and immediately post-intervention. As secondary outcomes, we assessed changes in depression and anxiety symptoms over the treatment period.<br><br>RESULTS: Sixty participants (mean age 43.8&#xa0;&#xb1;&#xa0;13.2 years, 71.7&#xa0;% women) were randomized to active tDCS&#xa0;+&#xa0;CT or sham tDCS&#xa0;+&#xa0;CT groups, and 52 finished the trial. Compared to sham, tDCS&#xa0;+&#xa0;CT resulted in significantly greater improvement in tests evaluating inhibitory control (effect size [ES]&#xa0;=&#xa0;0.07, 95&#xa0;% CI 0 to 0.23, p&#xa0;=&#xa0;0.046), processing speed (ES&#xa0;=&#xa0;0.08, 95&#xa0;% CI 0 to 0.25, p&#xa0;=&#xa0;0.034), and divided attention (ES&#xa0;=&#xa0;0.08, 95&#xa0;% CI 0 to 0.24, p&#xa0;=&#xa0;0.039), but not in tests evaluating other domains. Both groups improved similarly in depression and anxiety symptoms. Participant's and rater's active guess rates did not differ between groups (ps&#xa0;>&#xa0;0.20).<br><br>CONCLUSION: An intervention with prefrontal targeted tDCS&#xa0;+&#xa0;CT in patients with PASC with cognitive complaints might be effective in improving attention, processing speed and inhibitory control, although further studies are warranted to prospectively confirm these findings.<br><br>CLINICALTRIALS: GOV: NCT05389592.},
}
@article {pmid40846999,
year = {2025},
author = {Battaglia, DM and Post, CE and Yao, W and Wahl, A and Gralinski, LE and Liu, H and Dang, H and Madden, VJ and White, KK and Leist, SR and Dinnion, KH and De la Cruz, G and Midkiff, BR and Froggatt, HM and Gully, K and Zweigart, M and Reader, JR and Olstad, KJ and Everitt, JI and Van Rompay, KKA and De Paris, K and Sajti, E and Pickles, RJ and Browne, EP and Jones, CD and Boucher, RC and Baric, RS and Garcia, JV},
title = {SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation.},
journal = {Nature microbiology},
volume = {10},
number = {10},
pages = {2616-2630},
pmid = {40846999},
issn = {2058-5276},
support = {R01 HL160046/HL/NHLBI NIH HHS/United States ; R01 HL170183/HL/NHLBI NIH HHS/United States ; P51 OD011107/OD/NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; P51OD011107//U.S. Department of Health &amp; Human Services | NIH | NIH Office of the Director (OD)/ ; U19 AI171292/AI/NIAID NIH HHS/United States ; P01 AI117915/AI/NIAID NIH HHS/United States ; P01 HL108808/HL/NHLBI NIH HHS/United States ; P30 DK065988/DK/NIDDK NIH HHS/United States ; AI171292//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI110700/AI/NIAID NIH HHS/United States ; P01 AI117915-06S1//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {*COVID-19/pathology/virology/complications/immunology ; Animals ; Humans ; Mice ; *SARS-CoV-2 ; *Foam Cells/pathology/virology ; Lung/pathology/virology ; Macrophages/virology/pathology/immunology ; Macaca mulatta ; *Thrombosis/virology/pathology ; *Pulmonary Fibrosis/pathology/virology ; Disease Models, Animal ; Male ; Antiviral Agents/pharmacology ; },
abstract = {COVID-19 and long COVID are characterized by a dysregulated immune response. However, the role of macrophages during viral infection is poorly defined. Here we demonstrate that SARS-CoV-2 infection results in increased macrophage numbers and extensive formation of enlarged lipid-laden macrophages or foam cells using humanized mice, rhesus macaques and post-mortem human lung tissue. Notably, infection by other coronaviruses tested, SARS-CoV-1, MERS-CoV and two bat coronaviruses (SHC014-CoV or WIV1-CoV), did not result in macrophage proliferation or foam cell formation. Foam cells in SARS-CoV-2-infected human lung tissue display a pro-fibrotic and pro-thrombotic phenotype as they are enriched for genes associated with platelet activation and aggregation, as well as extracellular matrix organization and collagen synthesis. After viral clearance, macrophage numbers remain elevated, and lung fibrosis and thrombi persist. Importantly, we show that pre-exposure prophylaxis or early treatment with a SARS-CoV-2 antiviral, EIDD-2801, prevents increases in macrophage cell numbers and foam cell formation, and reduces fibrosis markers. These observations highlight the contribution of macrophages to lung inflammation and tissue injury leading to the pulmonary fibrosis observed in COVID-19 patients.},
}
@article {pmid40844210,
year = {2025},
author = {da Silva, RGL and Curi, A and Au, L and Capotescu, C and Eyal, G},
title = {Contested Illness and Alternative Expertise Networks in Global Health: Post-COVID Syndrome in Brazil.},
journal = {Sociology of health &amp; illness},
volume = {47},
number = {7},
pages = {e70079},
doi = {10.1111/1467-9566.70079},
pmid = {40844210},
issn = {1467-9566},
support = {//Facebook Research through Incite at Columbia University/ ; },
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/psychology ; Female ; Male ; Middle Aged ; Adult ; *Global Health ; SARS-CoV-2 ; Interviews as Topic ; Surveys and Questionnaires ; Social Media ; Post-Acute COVID-19 Syndrome ; },
abstract = {Contested illnesses such as long COVID or post-COVID syndrome create heightened uncertainty for patients as they navigate diagnosis and treatment. To lessen this uncertainty, patients in the United States and Europe have relied on patient activism and patient-led research to seek recognition from medical, scientific and political institutions. However, patients in other countries rely on different sets of strategies. Drawing on a survey (n = 144) and interviews (n = 32) of patients with post-COVID syndrome recruited via social media in Brazil, we found common experiences of psychologisation and dismissal of patient experiences. To combat this dismissal, some patients turned to each other online. However, patient groups showed a preference for advice from credentialled experts rather than asserting the embodied expertise of patients. Similarly, in the construction of alternative expertise networks, patients continued to rely on credentialled experts in the private healthcare system and from foreign and nonstate experts. We discuss how these alternative expertise networks may diminish the possibility of collective mobilisation and how those who are more socioeconomically disadvantaged and under-represented in our study will likely endure additional challenges.},
}
@article {pmid40843001,
year = {2025},
author = {Arcani, R and Brodovitch, A and Heim, X and Mège, JL and Bardin, N},
title = {Antiphospholipid antibodies during acute COVID-19 are not associated with long COVID: findings from a retrospective cohort study.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1634663},
pmid = {40843001},
issn = {1664-3224},
mesh = {Humans ; Female ; *Antibodies, Antiphospholipid/blood/immunology ; Male ; *COVID-19/immunology/blood ; Middle Aged ; Retrospective Studies ; Aged ; *SARS-CoV-2/immunology ; Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long COVID is a public health issue with complex pathophysiology, potentially involving immunoinflammatory and prothrombotic mechanisms. Antiphospholipid antibodies (aPL) have been observed in acute COVID-19 and speculated to contribute to long COVID development. Our goal was to determine if the presence of aPL was associated with the progression towards long COVID.<br><br>METHODS: We retrospectively analyzed all adult patients screened for aPL during acute COVID-19 in our institution between April 2020 and April 2022. Only patients with at least one follow-up &#x2265;3 months post-infection were included.<br><br>RESULTS: Among 114 patients (median age 64.0 years, 44.7% female), 19 (16.7%) developed long COVID. Those with long COVID were younger and more frequently admitted to ICU than those who recovered. However, aPL positivity did not differ significantly between patients with and without long COVID (63.2% vs. 66.3%, p = 0.79).<br><br>CONCLUSION: Our findings suggest no association between aPL and the development of long COVID. Prior associations may reflect confounding factors such as ICU admission.},
}
@article {pmid40842862,
year = {2025},
author = {Ai, J and Guo, J and Lin, K and Cai, J and Zhang, H and Zhu, F and Sun, G and Xue, Q and Zhu, K and Yang, Y and Yuan, G and Song, J and Fu, Z and Qi, X and Sun, Y and Lin, W and Qiu, C and Jiang, N and Wang, S and Zhang, W},
title = {Integrated multi-omics characterization across clinically relevant subgroups of long COVID.},
journal = {National science review},
volume = {12},
number = {8},
pages = {nwae410},
pmid = {40842862},
issn = {2053-714X},
abstract = {When SARS-CoV-2 became regional epidemics, a substantial number of patients suffered from post-acute sequelae of COVID-19 (PASC, aka long COVID). Exploring the pathogenesis and especially the heterogenicity features of long COVID subgroups is of paramount importance for understanding its etiology. In this study, through integrative multi-omics analyses encompassing transcriptomics, proteomics, and metabolomics, long COVID patients exhibited overall elevated MAPK pathway activation, while patients who have recovered from long COVID showed down-regulation of this response. Long COVID heterogenicity is described by multi-omics distinct signatures for each subgroup. The Multisystemic (MULTI) symptom subgroup is characterized by enhanced glycerophospholipid and ether lipid metabolism, Neurological (NEU) by augmented glycoprotein synthesis metabolism, Cardio cerebral (CACRB) by increased pyruvate metabolism and suppressed macrophage polarization, Musculoskeletal + Systemic (MSK + SYST) by elevated glycerophospholipid metabolism, and Cardiopulmonary (CAPM) by inhibited NF-κB signaling pathways. ABHD17A, CSNK1D, PSME4 and SYVN1 were general long COVID combination biomarkers, while CRH (MULTI), FPGT (NEU), CBX6 (CACRB) and RBBP4 (CAPM) were selected as serum-specific subgroup proteins. Our study provides a commonly shared and distinct pathophysiological explanation underpinning PASC, paving the way for future diagnosis and therapeutic interventions.},
}
@article {pmid40842528,
year = {2025},
author = {AlShamrani, M and Farahat, F and Assiri, A and AlHajjar, S and Albarrak, A and AlHashemi, H and AlZunitan, M and AlAqeel, M and AlYami, S and Memish, ZA},
title = {Consensus based recommendations for the management of post-COVID long-term sequelae (Long COVID): a regional perspective.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1453167},
pmid = {40842528},
issn = {2296-858X},
abstract = {BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic marks the biggest public health emergency of the 21[st] century. The long-term health issues linked to COVID-19, also known as Long COVID, pose a great challenge to patients and society. This article aims to highlight the current unmet clinical needs and present expert recommendations for region-specific assessment and management of Long COVID.<br><br>METHODS: A secondary desk research was performed focusing on global and regional guidelines for the assessment and management of Long COVID. The observations from the desk research form the foundation for the consensus statements. Additionally, an expert panel consisting of 10 consultant physicians from related specialties reviewed these guidelines and literature in advisory board meetings to identify unmet needs, bridge clinical gaps, and develop recommendations for the evaluation and management of Long COVID.<br><br>RESULTS: The expert recommendation statements were drafted based on overarching principles for the clinical assessment and management of Long COVID. The overarching principles used a targeted, multidisciplinary approach, and collaboration between multiple specialties of healthcare. The panel also highlighted the value of holistic care for the management of Long COVID.<br><br>CONCLUSION: Long COVID is a major public health challenge. These expert recommendations are expected to guide healthcare professionals in their clinical decision-making for the assessment, management, and appropriate rehabilitation of patients with Long COVID.},
}
@article {pmid40837716,
year = {2025},
author = {Escrivá, N and Moreno-Galarraga, L and Barado, E and Torres, MG and Fernandez-Montero, A},
title = {Association Between Acute COVID-19 Infection and Long COVID in a Non-Hospitalized Population: A Retrospective Case-Control Study.},
journal = {Health science reports},
volume = {8},
number = {8},
pages = {e71043},
pmid = {40837716},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: Long COVID (LC) is a condition characterized by the persistence of physical or psychological symptoms after acute SARS-CoV-2 infection. While its pathophysiology remains unclear, it is essential to identify acute-phase risk factors associated with its development. This study aimed to investigate the association between symptoms during acute COVID-19 and the risk of developing LC, and to evaluate the impact of LC on functional status in a nonhospitalized population.<br><br>METHODS: A retrospective observational case-control study was conducted between May 2022 and March 2024 including 434 participants with confirmed SARS-CoV-2 infection. Participants were classified as cases (those with LC; n&#x2009;=&#x2009;226) or controls (those without LC; n&#x2009;=&#x2009;208). Data were collected using a structured electronic form, including self-reported sociodemographic, clinical, and lifestyle information. Severity and number of acute symptoms were recorded. Functional status was assessed using the Post-COVID functional status (PCFS) Scale. Logistic and linear regression analyses were performed to explore associations, adjusted for potential confounders.<br><br>RESULTS: Severe acute COVID-19 (defined as pneumonia or hospitalization) was associated with a significantly increased risk of LC (adjusted OR&#x2009;=&#x2009;7.22; 95% CI: 2.79-18.70). Additionally, each additional symptom during the acute phase increased the odds of LC by 52% (adjusted OR&#x2009;=&#x2009;1.52; 95% CI: 1.35-1.77). Dyspnea and chest pain were the symptoms most strongly associated with LC.<br><br>CONCLUSION: The severity and symptom burden of acute COVID-19 are strongly associated with the development of LC and with long-term functional impairment. These findings highlight the importance of early identification and follow-up in patients with severe initial COVID-19 symptoms.},
}
@article {pmid40836768,
year = {2025},
author = {Al-Jabr, H and Castle, DJ and Thompson, DR and Windle, K and Belcher, J and Valenzuela, MMI and Helliwell, T and Ski, CF},
title = {Long COVID Optimal Health Programme to Enhance Mental and Physical Health: A Feasibility Randomised Controlled Trial.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70399},
pmid = {40836768},
issn = {1369-7625},
support = {//This study was supported by Mental Health Alliance (East Suffolk, West Suffolk and North East Essex) (SIV02/0000555)./ ; },
mesh = {Humans ; Female ; Feasibility Studies ; Male ; *COVID-19/psychology/complications ; Middle Aged ; *Mental Health ; Adult ; United Kingdom ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: Long COVID (LC) is characterised by fatigue, muscle weakness and impaired concentration among other symptoms. No standardised diagnostic or treatment pathway is yet available, though a holistic, person-centred approach to symptom management is recommended. The LC Optimal Health Programme (LC-OHP) is a psychoeducational programme designed to support the mental and physical health of people with LC. This study aimed to examine the feasibility of delivering the LC-OHP to people with LC.<br><br>METHODS: This was a feasibility randomised controlled trial of the LC-OHP conducted across the UK. Adults diagnosed with LC were recruited and randomised to control (usual care) or to intervention (LC-OHP) groups; follow-up questionnaires were completed at three- and 6-months (December 2021 to May 2023).<br><br>RESULTS: Sixty participants were recruited with a completion rate of 83% (n&#x2009;=&#x2009;50). Most participants in the LC-OHP group completed programme sessions (n&#x2009;=&#x2009;19, 68%), rated the programme positively (n&#x2009;=&#x2009;23, 87%); and felt that it had potential to improve health outcomes (n&#x2009;=&#x2009;42, 70%). Initial findings demonstrate improvements across all variables at 3- and 6-months, and more so for the LC-OHP group than the control group in the short-term.<br><br>CONCLUSION: Findings support the feasibility of delivering the LC-OHP to people with LC. Further, initial data demonstrate potential for the programme to improve most outcomes at three and 6 months. Data from this feasibility trial will be used as an evidence base to support a fully powered RCT of the LC-OHP on patients with LC.<br><br>The LC-OHP programme was adapted from the original OHP. Taking into account the various symptoms that people with LC experience, including fatigue and brain fog, public members were not directly involved in the design of the study; however, several approaches were considered to obtain ongoing support from public members while conducting the study, to suit people with LC. This included consulting with practitioners who care for people with LC and implementing their feedback, implementing prior feedback from patients with other chronic health conditions who used the OHP in previous studies, and collecting and implementing feedback from participants receiving this programme in this study. Additionally, two public members with lived LC experience were members of the data management committee that overviewed the study progress and provided continuous support. Public members and practitioners provided advice and guidance on different aspects related to the LC-OHP programme and to the process of delivering it to study participants. This included making the programme concise, visual, colourful, and more user-friendly, and adjusting and adapting the mode and timing of delivering the programme sessions (i.e., reduce the session duration, use convenient delivery methods) as preferred by study participants.<br><br>TRIAL REGISTRATION: ISRCTN trial register: registration number 38746119, https://doi.org/10.1186/ISRCTN38746119.},
}
@article {pmid40834724,
year = {2026},
author = {Abbas, U and Ahmed, I and Khalid, MU and Hafeez, S and Mukhtiar, S and Hussain, N and Nasrumminallah, M and Khan, MS and Babar, N and Ashraf, S and Kumar, P},
title = {Biochemical Profile of Recovered Individuals with Mild COVID-19: A Cross-Sectional View at Two Different Time Points.},
journal = {Archives of medical research},
volume = {57},
number = {1},
pages = {103286},
doi = {10.1016/j.arcmed.2025.103286},
pmid = {40834724},
issn = {1873-5487},
mesh = {Humans ; *COVID-19/blood ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; Adult ; SARS-CoV-2 ; Alanine Transaminase/blood ; Biomarkers/blood ; Time Factors ; Case-Control Studies ; Interleukin-6/blood ; Aged ; Alkaline Phosphatase/blood ; Hemoglobins/analysis ; Leukocyte Count ; },
abstract = {AIM: This study was designed to cross-sectionally evaluate the frequency of long COVID-19, along with their hematological and biochemical parameters in survivors of mild COVID-19 after 6-15 months of acute infection.<br><br>METHODS: We recruited 75 age-matched healthy controls (HC) and 150 individuals who had recovered from mild cases of COVID-19. The recovered individuals were grouped according to the time elapsed since acute infection: 6-10 month (CoV_A) and >10-15 month of recovery (CoV_B). A brief clinical history was taken and detailed hematological and biochemical blood parameters were measured.<br><br>RESULTS: In our study, 64% of individuals had symptoms of long COVID. There were differential symptoms and presenting complaints associated with time since acute infection. The recovered group had significantly different hemoglobin concentration, red blood cell (RBC) count, white blood cell (WBC) count, lymphocyte, interleukin-6 (IL-6), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and vitamin D3 levels, compared with the healthy controls (p <0.05). Differences were also found between the 6-10 months and the >10-15 month recovery groups (p <0.05).<br><br>CONCLUSION: Differential biochemical markers related to the time elapsed since acute infection show a different metabolic and biochemical status of the host at different time points after infection. Moreover, the pathophysiological pathways involved in these dysregulated biochemical markers should also be studied in relation to the long term impact of COVID-19 infection.},
}
@article {pmid40833451,
year = {2025},
author = {Chandler, D and Abramoff, B and Bramson, C and Cappelleri, JC and Chohan, A and Harrington, M and Jamal, H and Lusk, J and Mazar, I and Paredes, R and Tatlock, S and Ustianowski, A and Weinstein, E and Mokgokong, R},
title = {Development and content validation of the Long COVID/ post-acute sequelae of COVID-19 (PASC) patient-reported outcome (PRO) instrument.},
journal = {Journal of patient-reported outcomes},
volume = {9},
number = {1},
pages = {105},
pmid = {40833451},
issn = {2509-8020},
mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Female ; Male ; SARS-CoV-2 ; Middle Aged ; Reproducibility of Results ; Qualitative Research ; Quality of Life ; Adult ; Aged ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) or Long COVID is a post-viral complication of SARS-CoV-2 infection, causing ongoing symptoms and impaired function over a prolonged period of time. There is limited understanding of how the signs and symptoms of Long COVID/PASC affect patients' lives and how to measure them, which is essential when developing care strategies. This study aimed to develop and evaluate the content validity for a novel patient-reported outcome (PRO) instrument in Long COVID/PASC through qualitative research, which was informed by the patient experience of Long COVID/PASC and both patient and clinician input.<br><br>METHODS: A review of literature and PRO instruments developed for Long COVID/PASC identified measurement gaps for the context of use (i.e., weekly assessment of signs/symptoms in clinical trial research). This informed the development of the preliminary Long COVID/PASC PRO instrument, which was tested via patient interviews (combined concept elicitation and cognitive debriefing) to align with regulatory standards, and discussions with clinical experts were conducted to provide clinical insights. The final instrument was modified based on this input to further promote its content validity.<br><br>RESULTS: Thirty participants were interviewed about their Long COVID/PASC experiences. Participants most frequently reported experiencing tiredness after physical activity (n&#x2009;=&#x2009;29/30; 97%), general tiredness (n&#x2009;=&#x2009;28/30; 93%), shortness of breath (n&#x2009;=&#x2009;25/30; 83%), cough (n&#x2009;=&#x2009;23/30; 77%) and muscle/body aches (n&#x2009;=&#x2009;23/30; 77%). All participants reported that Long COVID/PASC had an impact on their health-related quality of life. Almost all (n&#x2009;=&#x2009;27/28; 96%) sign/symptom concepts were reported in the first three sets of interviews suggesting conceptual saturation was achieved. Items, response options and the recall period of the preliminary Long COVID/PASC PRO instrument were understood as intended (&#x2265;&#x2009;90%) and relevant to most participants across both rounds (&#x2265;&#x2009;47%). Modifications were made to the instrument following patient input, resulting in the 18-item Long COVID/PASC instrument. Clinician input (n&#x2009;=&#x2009;3) corroborated participant interview results, supporting the content validity of the Long COVID/PASC PRO instrument.<br><br>CONCLUSION: The Long COVID/PASC PRO instrument has been developed in line with regulatory standards and the qualitative evidence demonstrated strong content validity in a Long COVID/PASC population. Research to evaluate psychometric properties will provide further evidence of the instrument's measurement properties.},
}
@article {pmid40833176,
year = {2025},
author = {Rafałowicz, J and Wagner, L and Rafałowicz, B},
title = {Lesions located on the tongue after SARS-CoV-2 infection: A retrospective study.},
journal = {Dental and medical problems},
volume = {62},
number = {4},
pages = {619-626},
doi = {10.17219/dmp/179008},
pmid = {40833176},
issn = {2300-9020},
mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Retrospective Studies ; *Tongue Diseases/etiology/pathology/virology ; Middle Aged ; Adult ; Aged ; *Tongue/pathology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: The post-coronavirus disease (post-COVID) syndrome (PCS), which occurs after severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection, can manifest a variety of symptoms in the oral cavity. Changes to the tongue tend to persist longer than other symptoms in this area.<br><br>OBJECTIVES: The aim of the study was to present the changes and lesions that occur on the tongue after SARS-CoV-2 infection, as well as their healing as a consequence of the therapy used or lack thereof.<br><br>MATERIAL AND METHODS: The study sample included 426 individuals who had contracted SARS-CoV-2 and presented with changes on the tongue. Periodic checkups enabled to determine their variability and duration in response to treatment or lack thereof.<br><br>RESULTS: The presence of various oral manifestations was reported, including strawberry tongue (women (F): 143; men (M): 65), depapillation (F: 86, M: 156), geographic tongue (F: 65, M: 124), vascular changes (F: 102, M: 46), aphthous changes (F: 106, M: 58), candidiasis (F: 89, M: 57), edema (F: 42, M: 52), herpetic lesions (F: 38, M: 49), ulcers (F: 38, M: 46), erosions (F: 32, M: 28), nodular lesions (F: 6, M: 19), and necrotic changes (F: 9, M: 7). Fungiform papillae were found to be enlarged in 189 women and 213 men. On average, from 3 to 5 changes were identified concurrently. In the majority of cases, the changes disappeared on their own and persisted from 4 weeks to 36 months. In 20% of cases, they recurred. Local therapy resulted in a 50% reduction in the duration of PCS.<br><br>CONCLUSIONS: Changes that manifest on the tongue require observation and basic or specialized treatment. In the absence of pain, monitoring is recommended for a period of 4 weeks, after which a spontaneous disappearance should be expected. In the event that various changes occur in the oral cavity, the patient should be referred for specialized treatment.},
}
@article {pmid40832812,
year = {2025},
author = {Ableidinger, S and De Gennaro, L and Mota-Rolim, S and Scarpelli, S and Bolstad, CJ and Bjorvatn, B and Espie, CA and Dauvilliers, Y and Korman, M and Landtblom, AM and Plazzi, G and Matsui, K and Yordanova, J and Bjelajac, AK and Reis, C and Chung, F and Merikanto, I and Wing, YK and Partinen, M and Macêdo, T and Nadorff, MR and Holzinger, B},
title = {Lucid Dreaming: Not Just Awareness, but Agency.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e70181},
doi = {10.1111/jsr.70181},
pmid = {40832812},
issn = {1365-2869},
abstract = {During lucid dreaming (LD), dreamers are aware that they are dreaming and may be able to influence the oneiric content. There has been recent debate about the relative importance of the ability to influence the dream and having agency over the pure awareness of dreaming. To underline this, we examined the associations of lucid dreams without agency (LD-Ag) and lucid dreams with agency (LD + Ag) to sleep and mental health problems and long COVID during the pandemic. We collected data in 16 countries on four continents from May to December 2021 on 10,715 subjects. Logistic regression was performed to predict LD-Ag and LD + Ag, with a sample of 8133 participants. We found that 30% of the participants frequently knew they were dreaming during the pandemic. About half of those (17%) reported that they could influence their dreams. Female gender and anxiety symptoms were negatively associated with LD + Ag. Dream recall, nightmares, insomnia, dream enactment behaviour (DEB), sleep vocalisation, short and long COVID and PTSD were positively associated with LD + Ag. Old age, dream recall, nightmares and anxiety symptoms were positively associated with LD-Ag, while short sleep length, being an evening type, and short COVID were negatively associated with LD-Ag. The different associations for LD-Ag and LD + Ag suggest that they may be distinct sleep states. This is also the first study to show that both COVID-19 and long COVID are associated with LD.},
}
@article {pmid40832427,
year = {2025},
author = {Bramante, CT and Stewart, TG and Boulware, DR and McCarthy, MW and Gao, Y and Rothman, RL and Mourad, A and Thicklin, F and Cohen, JB and Garcia Del Sol, IT and Shah, NS and Mehta, M and Quintero Cardona, O and Scott, J and Ginde, AA and Castro, M and Jayaweera, D and Sulkowski, M and Gentile, N and McTigue, K and Felker, GM and Collins, S and Dunsmore, SE and Adam, SJ and Lindsell, CJ and Hernandez, AF and Naggie, S and , },
title = {Metformin on the Presence of COVID-19 Symptoms Over 6 Months: The ACTIV-6 Randomized Clinical Trial.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.08.25333305},
pmid = {40832427},
abstract = {BACKGROUND: The effect of metformin on preventing long-term COVID-19 symptoms among low-risk adults has not been studied. The objective of this study was to Assess metformin compared with placebo during acute SARS-CoV-2 infection on the presence of COVID-19 symptoms 180 days later.<br><br>METHODS: The ACTIV-6 platform evaluated repurposed medications for mild to moderate COVID-19. Between September 19, 2023 and May 1, 2024, 2983 outpatient adults &#x2265;30 years with confirmed SARS-CoV-2 infection and &#x2265;2 COVID-19 symptoms for &#x2264;7 days were included from 90 sites. Participants were randomized to metformin (titrated to 1500 mg daily) or placebo for 14 days. Post-acute sequelae of SARS-CoV-2 or death (PASCD) was ascertained by asking whether participants had symptoms they attributed to COVID-19 on day 180. Secondary outcomes included clinician diagnosis of long COVID. For the primary outcome, the single-sided threshold for efficacy was 0.975.<br><br>RESULTS: Among 2983 participants, the median age was 47 years (interquartile range [IQR] 38-57); 63% were female; 47% Hispanic/Latino; 83% reported &#x2265;1 prior COVID-19 infections or SARS-CoV-2 vaccines. There were no deaths. Overall, 96 (3.2%) reported COVID-19 symptoms on day 90, 101 (3.4%) on day 120, and 79 (2.6%) on day 180. The covariate-adjusted risk of PASCD on day 180 was lower in the metformin group (-0.008; 95% credible interval [CrI] -0.022 to 0.006; posterior probability of efficacy [PPE] 0.83), compared with the placebo group with an adjusted risk ratio of 0.79 (95% CrI 0.474 to 1.230). The risk of clinician diagnosis of long COVID (secondary outcome) on day 180 was lower in the metformin group (-0.007; 95% CrI -0.015 to 0.001; PPE 0.96), with a relative risk of 0.495 (95% CrI 0.155 to 0.995).<br><br>CONCLUSIONS: The posterior probability of efficacy for metformin preventing the primary endpoint did not exceed the prespecified threshold of 0.975 for declaring efficacy. Secondary outcomes were numerically better with metformin.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov (NCT04885530).},
}
@article {pmid40832415,
year = {2025},
author = {Kehl-Floberg, K and Freisberg, E and Pop-Vicas, A and Gangnon, R and Edwards, DF},
title = {Long COVID risk by pre-infection symptoms and functional status: A retrospective cohort study of data from the All of Us Research Program.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40832415},
support = {OT2 OD026556/OD/NIH HHS/United States ; TL1 TR002375/TR/NCATS NIH HHS/United States ; U2C OD023196/OD/NIH HHS/United States ; OT2 OD025315/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; OT2 OD026549/OD/NIH HHS/United States ; OT2 OD025337/OD/NIH HHS/United States ; OT2 OD025277/OD/NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; OT2 OD023205/OD/NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; },
abstract = {IMPORTANCE: Over seven million U.S. adults experience "long COVID", or persistent health issues after COVID-19. Multiple guidelines recommend the inclusion of functional status in long COVID diagnostic criteria, but more evidence is needed to guide this recommendation. This study explores the adjusted odds of developing long COVID by pre-infection symptoms and functional status, and the feasibility of estimating functional status using health records data. DESIGN: Retrospective cohort study in a multicenter national longitudinal cohort of U.S. adults with history of COVID-19, using health records and survey responses through July 2022 (All of Us CDR 7.0).<br><br>EXPOSURES: Pre-infection (-5 years) incidences of (a) at least one symptom common in long COVID, and (b) functional status, indicated by All of Us baseline survey responses and diagnostic/procedure/billing codes. Disease and demographic data covariates were included in the adjusted models.<br><br>RESULTS: N = 65,464 met inclusion criteria (n=40,655 had post-infection occurrences of at least one symptom (long COVID group), while n=24,809 had none). Adjusted odds ratios within 99% confidence intervals [99% CI] of developing long COVID increased with lower pre-infection self-reported mental health ("Good" compared to "Excellent" AOR=1.14 [1.04,1.25], P>0.000), and more pre-infection symptoms (compared to the median of four, people with zero had much lower odds (AOR=0.15 [0.04,0.61], P=0.008). Adjusted odds were not significantly affected by any single pre-infection symptom, self-rated physical ability, or clinical documentation of functional impairment.<br><br>CONCLUSIONS: Greater pre-illness symptom burden and lower self-rated mental health increased the odds of long COVID symptoms, after adjusting for demographics, variant, functional status, and individual symptoms. Long COVID represents a change from baseline functioning and health, even in people with pre-infection incident symptoms and functional impairments. This estimation of pre-infection functional status using harmonized electronic health records data demonstrated the feasibility of these data in developing the diagnostic utility of functional status changes in long COVID.},
}
@article {pmid40831631,
year = {2025},
author = {Zydek, I and Thümmler, L and Beckmann, N and Sehl, C and Soddemann, M and Grüneberg, R and Elsner, C and Kamler, M and Dittmer, U and Witzke, O and Kadow, S and Gulbins, E and Becker, KA and Krawczyk, A},
title = {Amitriptyline potently neutralizes distinct SARS-CoV-2 variants including D614G, Omicron BA.5, and Omicron XBB.1.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1631947},
pmid = {40831631},
issn = {1664-302X},
abstract = {INTRODUCTION: COVID-19, caused by SARS-CoV-2, remains a global health challenge despite the availability of vaccines and antiviral treatments. The emergence of immune escape variants and the persistence of long COVID symptoms continue to complicate prevention and therapy, especially in low-resource settings. Functional inhibitors of acid sphingomyelinase (FIASMAs) have shown promise as broad-spectrum antiviral agents.<br><br>METHODS: We evaluated the antiviral efficacy of amitriptyline, a widely used antidepressant and known FIASMA, against SARS-CoV-2. In vitro neutralization assays using pseudotyped virus-like particles (VLPs) and clinical isolates were performed to assess its ability to inhibit viral entry and replication.<br><br>RESULTS: Amitriptyline significantly inhibited infection by SARS-CoV-2 VLPs bearing spike proteins, including those with mutations in the receptor-binding domain. Moreover, it reduced replication of clinical SARS-CoV-2 isolates D614G, Omicron BA.5, and Omicron XBB.1 in a dose-dependent manner at subtoxic concentrations.<br><br>DISCUSSION: Our findings demonstrate that amitriptyline neutralizes SARS-CoV-2 across multiple variants. These results support the potential of amitriptyline as a repurposed antiviral drug. Further clinical studies are warranted to evaluate its efficacy and safety in treating COVID-19 in humans.},
}
@article {pmid40830954,
year = {2025},
author = {Büchner, R and Sander, C and Schindler, S and Walter, M and Scheibenbogen, C and Schomerus, G},
title = {"Have you considered that it could be burnout?"-psychologization and stigmatization of self-reported long COVID or post-COVID-19 vaccination syndrome.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {488},
pmid = {40830954},
issn = {1741-7015},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Anxiety/psychology ; *COVID-19/psychology/prevention &amp; control ; *COVID-19 Vaccines/adverse effects ; Cross-Sectional Studies ; Depression/psychology ; Loneliness/psychology ; Self Concept ; Self Report ; *Social Stigma ; },
abstract = {BACKGROUND: People reporting long COVID (LC) or post-COVID-19 vaccination syndrome (PCVS) not only suffer from their symptoms but also from stigmatization. Despite ample account and characterization of stigma experiences so far, its mechanisms and consequences on health outcomes, and particularly the role of "psychologization" remain unclear.<br><br>METHODS: In a cross-sectional observational study, we examined a large convenience sample of adults who report having LC or PCVS. We translated and adapted the "Long Covid Stigma Scale" to measure stigmatization. We measured generally perceived and personally experienced psychologization with newly developed scales/items. Outcome measures included disclosure concerns, loss of trust in medicine, life satisfaction, depression, anxiety, self-esteem, and loneliness. We calculated overall prevalences of stigma and psychologization and their correlations with the outcomes. Using mediation analysis with SEM, we tested the hypothesis that psychologization of LC and PCVS syndromes causes harm by increasing stigmatization.<br><br>RESULTS: Altogether, N&#x2009;=&#x2009;2053 individuals (68% reporting LC, 32% reporting PCVS) were included in the analyses. The overall prevalences of stigma experiences were high: 83% of those reporting LC and 90% of those reporting PCVS experienced stigma. Prevalences of perceived psychologization (LC: 87%, PCVS: 91%) and experienced psychologization (LC: 82%, PCVS: 87%) were similarly high. Both stigmatization and psychologization were positively correlated with disclosure concerns, loss of trust in medicine, depression, anxiety, and loneliness as well as negatively correlated with life satisfaction and self-esteem. Mediation analysis indicated that stigmatization mediated a relevant proportion of the relationship between psychologization and negative outcomes.<br><br>CONCLUSIONS: People reporting LC or PCVS are subject to stigmatization and psychologization. From a patient perspective, psychologization appears to be an important driver of stigmatization and negative outcomes.},
}
@article {pmid40830439,
year = {2025},
author = {Jyonouchi, H and Kornitzer, J and Geng, L},
title = {Favorable responses to upadacitinib, a JAK1 inhibitor, in long COVID patients with predominant neuropsychiatric symptoms: case reports in 2 autistic patients and one typically developing patient.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {342},
pmid = {40830439},
issn = {1471-2377},
mesh = {Humans ; *Autism Spectrum Disorder/complications/drug therapy ; *COVID-19/complications/psychology ; *COVID-19 Drug Treatment ; *Heterocyclic Compounds, 3-Ring/therapeutic use ; *Janus Kinase 1/antagonists &amp; inhibitors ; Janus Kinase Inhibitors/therapeutic use ; },
abstract = {The long-term impact of coronavirus disease 2019 (COVID-19) has become evident over the past 3-4 years, with the recognition of post-COVID long-term sequelae, often referred to as long COVID. Neuropsychiatric symptoms are one of the hallmarks of long COVID. In severe cases, it can even present features of encephalopathy. Since some of the neuropsychiatric symptoms associated with long COVID overlap symptoms found in neuropsychiatric disorders, it has been difficult to sort out the effects of long COVID in such subjects. This is especially true in patients diagnosed with autism spectrum disorders (ASD), given their difficult behavioral symptoms and other co-morbid conditions. COVID-19 is thought to affect the onset or progress of encephalopathy symptoms by activation of the immune system through the type 1 interferon (IFN) signaling pathway. In that case, treatment would require an immunomodulating agent that targets such pathways. However, such measures may not be applied to ASD subjects, in whom long COVID may not even be considered as the cause of their symptoms. In this study, we present the beneficial effects of upadacitinib, a JAK (janus kinase) 1 inhibitor, that blocks downstream signaling of type 1 IFNs, on 3 patients, 2 with ASD and one without ASD. In these patients, long COVID was thought to have triggered or aggravated encephalopathy-like symptoms. The beneficial effects of upadacitinib were not only noted by an improvement of their behavioral symptoms but also shown by an improvement of monocyte cytokine profiles (less activated state); peripheral blood monocytes were used as surrogates of microglial cells. These three cases presented highlight a possible use of JAK inhibitors for treating long COVID-associated neuropsychiatric symptoms in both ASD and non-ASD subjects. The presented cases highlight the inherent difficulty of diagnosing long COVID in ASD cases.},
}
@article {pmid40828804,
year = {2025},
author = {Wasilewski, MB and Leighton, J and Reis, L and Vijayakumar, A and English, M and Sanchez, K and Hitzig, SL and Nelson, MLA and Sheppard, C and Robinson, L and Steinberg, R and Nguyen, M and Bayley, M and Daneman, N and Levy, C and Goulding, S and Ho, C and Simpson, R},
title = {Coping with stressful life disruptions due to long COVID: A qualitative study.},
journal = {PloS one},
volume = {20},
number = {8},
pages = {e0329831},
pmid = {40828804},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/psychology ; Female ; Male ; Middle Aged ; *Adaptation, Psychological ; *Caregivers/psychology ; *Stress, Psychological/psychology ; Qualitative Research ; Adult ; Aged ; SARS-CoV-2 ; Quality of Life ; },
abstract = {BACKGROUND: Long COVID impacts people's physical health and cognition which immensely affects their psychosocial well-being. A larger study was conducted that explored the psychosocial impacts of Long COVID on individuals and caregivers. This paper focuses on the impact of these stressful disruptions on one's health and psychosocial well-being, and how individuals cope with them.<br><br>METHODS: Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with Long COVID (mean age: 50.4) and 15 caregivers (mean age: 50.0)). People with Long COVID and caregivers were recruited from healthcare institutions through care team referrals, patient partners, and health organizations and via social media platforms. A thematic codebook developed through inter-coder agreement processes was used to analyze the data.<br><br>FINDINGS: Three key themes were identified: (1) Disruptions in people with Long COVID and caregivers' lives are characterized by a deviation from their perceived 'normalcy', (2) Disruptions lead to substantial stress, loss and grief (independence, agency, meaning, and purpose), and (3) People with Long COVID and caregivers cope with stressful disruptions by adapting their daily activities.<br><br>CONCLUSION: Our findings make the case for supportive rehabilitation strategies that address the psychosocial repercussions of Long COVID to help mitigate feelings of loss and grief, thereby increasing individuals' overall quality of life and well-being.},
}
@article {pmid40827018,
year = {2025},
author = {Ford, ND and Dalton, AF and Edwards, D and King, H and Luckhaupt, SE and Ma, KC and Slaughter, D and Silver, SR and Saydah, S},
title = {Employment Status, Work Limitations, Cognitive Dysfunction, and Sickness Absenteeism Among US Adults With and Without Long COVID.},
journal = {American journal of industrial medicine},
volume = {68},
number = {10},
pages = {909-919},
doi = {10.1002/ajim.70014},
pmid = {40827018},
issn = {1097-0274},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; Male ; Adult ; Female ; Middle Aged ; United States/epidemiology ; *COVID-19/epidemiology/complications ; *Absenteeism ; *Employment/statistics &amp; numerical data ; *Cognitive Dysfunction/epidemiology ; Cross-Sectional Studies ; *Sick Leave/statistics &amp; numerical data ; SARS-CoV-2 ; Young Adult ; Adolescent ; Prevalence ; Aged ; Health Surveys ; },
abstract = {INTRODUCTION: Long COVID may limit people's ability to carry out daily activities, including work. Little is known about the potential effect of long COVID on work limitations and absenteeism. We describe employment status and characteristics, work limitations, cognitive dysfunction, and sickness absenteeism among adults with and without long COVID.<br><br>METHODS: Using data from the cross-sectional 2022 National Health Interview Survey, we estimated the prevalence (95% confidence intervals [CI]) of work-related outcomes by long COVID status among US adults &#x2265;&#x2009;18 years (n&#x2009;=&#x2009;26,270). Among employed adults with prior COVID-19 illness, we estimated crude and adjusted odds ratios for work limitations (compared to no limitations), cognitive dysfunction (some or a lot of difficulty with memory or concentration compared to no difficulty), and sickness absenteeism (&#x2009;&#x2265;&#x2009;11 sick days compared to 0-10 days) in the prior year. All estimates account for survey design and are weighted to the US noninstitutionalized population. Analyses were conducted in 2024.<br><br>RESULTS: 3.4% of adults reported long COVID. Adults with long COVID more often reported being unable to work due to health or disability compared to adults without long COVID (p&#x2009;=&#x2009;0.0006). Among employed adults with prior COVID-19 illness, long COVID was associated with higher odds of work limitations (aOR 1.3, 95% CI 1.1-1.5), cognitive dysfunction (aOR 1.3, 95% CI 1.1-1.5), and sickness absenteeism (aOR 1.4, 95% CI 1.2-1.5) compared to those who did not develop long COVID.<br><br>CONCLUSIONS: Long COVID was associated with work limitations, cognitive dysfunction, and sickness absenteeism among employed US adults. Workplace accommodations may be important considerations for people with long COVID.},
}
@article {pmid40822592,
year = {2025},
author = {Takada, K and Trinh, QD and Takeda, Y and Tsuji, NM and Hayakawa, S and Komine-Aizawa, S},
title = {Heat-killed Lactobacillus acidophilus suppresses SARS-CoV-2 infection in the human intestinal epithelial cell line Caco-2.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1556344},
pmid = {40822592},
issn = {2235-2988},
mesh = {Humans ; *Lactobacillus acidophilus/physiology ; Caco-2 Cells ; *SARS-CoV-2/physiology ; *Probiotics/pharmacology ; COVID-19/virology/prevention &amp; control ; Epithelial Cells/virology/microbiology ; Hot Temperature ; Intestinal Mucosa/virology/microbiology ; Antiviral Agents/pharmacology ; },
abstract = {BACKGROUND: The gastrointestinal (GI) tract is suspected to be a possible source for the systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as a reservoir of long coronavirus disease (COVID). Thus, the mucosal epithelial tissue of the colon is a potential target for probiotics to help control SARS-CoV-2 infection. Recently, the effect of live probiotics on COVID-19 has been evaluated. However, live probiotics have certain risks, including the transmission of antibiotic-resistant genes, disturbance of gut colonization in infants, and systemic infections induced by translocation. Therefore, there is growing interest in nonviable microorganisms, particularly heat-killed probiotic bacteria, to mitigate these risks.<br><br>METHODS: This study evaluated the antiviral properties of heat-killed Lactobacillus acidophilus (HK-LA) in the Caco-2 cell line. Caco-2 cells were infected by SARS-CoV-2 with or without 24-hour pretreatment of HK-LA and the presence of HK-LA during infection.<br><br>RESULTS: RT-qPCR analysis showed that HK-LA treatment significantly reduced SARS-CoV-2 genome copies by approximately 30%. Similarly, flow cytometry revealed a roughly 30% decrease in SARS-CoV-2 spike-positive Caco-2 cells following HK-LA treatment. Additionally, ELISA demonstrated a significant increase in IFN-&#x3bb;2 secretion induced by HK-LA.<br><br>DISCUSSION: HK-LA reduces viral infection in Caco-2 cells with an increase in IFN-&#x3bb;2 secretion. Therefore, heat-killed lactobacilli could potentially reduce SARS-CoV-2 infection in the GI tract, suggesting a possible clinical application.},
}
@article {pmid40821912,
year = {2025},
author = {Hata, R and Sugawara, H and Hayashi, R and Okamoto, Y and Nishihara, R and Yamasaki, T and Hatanaka, A and Harada, K and Hori, H},
title = {Trichotillomania in long COVID successfully treated with escitalopram: A case report.},
journal = {PCN reports : psychiatry and clinical neurosciences},
volume = {4},
number = {3},
pages = {e70190},
pmid = {40821912},
issn = {2769-2558},
}
@article {pmid40821130,
year = {2025},
author = {Oakley, DS and Mortazavi, M and Rivera, DK and Samsam, L and Seitz, TP and Streeter, L},
title = {Assessing Brain Neurophysiology in COVID-19 Patients With Prolonged Cognitive Fatigue: A Comparison With Persistent Post-concussion Symptoms.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88160},
pmid = {40821130},
issn = {2168-8184},
abstract = {INTRODUCTION: Brain fog and cognitive dysfunction are frequently reported in post-viral fatigue syndromes such as long COVID, yet these symptoms remain challenging to quantify objectively. Notably, many individuals with long COVID describe clinical features that overlap with those observed in patients with persistent post-concussion symptoms (PPCS), including cognitive fatigue, exertional intolerance, mood disturbances, visual and balance problems, headaches, and neck pain. Emerging evidence suggests that PPCS is associated with distinct electrophysiological abnormalities, including altered functional connectivity (measured by electroencephalography (EEG) coherence), spatial changes in EEG amplitude distribution (notably increased frontal alpha and left-right asymmetry), and reduced cognitive evoked potentials (e.g., the auditory P300 response). In this study, we investigated whether these electrophysiological markers of PPCS are also present in individuals experiencing post-viral fatigue following COVID-19, aiming to provide objective measures to better characterize and quantify cognitive impairment in this population.<br><br>MATERIALS AND METHODS: Thirty-one patients (mean age 45 &#xb1; 9 years) reporting persistent neurocognitive symptoms following COVID-19 infection (10 &#xb1; 2 months post-infection) were evaluated at intake to a brain injury clinic while seeking assessment/treatment for prolonged cognitive complaints. Over this time period, 64 PPCS patients (69% female; age: 42 &#xb1; 11 years) were evaluated at the same clinic for concussion-related symptoms using identical protocols. These were compared to seventy age-matched controls (mean age 45 &#xb1; 5 years) without a history of COVID-19 or neurological conditions. Assessments comprised standard concussion assessments with symptom profiles that included cognitive fatigue and EEG with event-related potentials (ERP). We then compared the EEG and ERP metrics known to be sensitive to declines in mental performance (i.e., PPCS) for both the long COVID group and age-matched controls.<br><br>RESULTS: The long COVID cohort demonstrated neurophysiological alterations paralleling those observed in PPCS, including significantly impaired processing speed and reduced physical reaction times compared to controls (p < 0.001), as well as cognitive electrophysiological deficits, such as attenuated P300 amplitudes, which reflect impaired attention allocation (p < 0.001). These biomarkers normalized concomitantly with symptom resolution at long-term follow-up (mean 20 &#xb1; 8 months post-baseline assessment).<br><br>CONCLUSIONS: Our data demonstrate that ERP&#xa0;deficits, characteristic of cognitive decline in conditions like concussion, PPCS, and aging, are replicable in long COVID patients. Notably, these electrophysiological abnormalities (reduced P300 amplitude and altered coherence) correlate with quantifiable cognitive fatigue and functional neurological impairments. Biomarker normalization tracked with symptom resolution at follow-up (20 &#xb1; 8 months), confirming their clinical relevance. These accessible metrics provide objective parameters to identify virally induced cognitive deficits, addressing a critical need for validated diagnostic tools in post-viral syndromes.},
}
@article {pmid40819656,
year = {2025},
author = {Bruno, RM and Badhwar, S and Abid, L and Agharazii, M and Anastasio, F and Bellien, J and Burghuber, O and Faconti, L and Filipovsky, J and Ghiadoni, L and Giannattasio, C and Hametner, B and Hughes, AD and Jeroncic, A and Ikonomidis, I and Lonnebakken, MT and Maloberti, A and Mayer, CC and Muiesan, ML and Paini, A and Panayiotou, A and Park, C and Rajkumar, C and Becerra, CR and Spronck, B and Terentes-Printzios, D and Tuncok, Y and Weber, T and Boutouyrie, P and , },
title = {Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study.},
journal = {European heart journal},
volume = {46},
number = {39},
pages = {3905-3918},
pmid = {40819656},
issn = {1522-9645},
support = {//the Artery Society/ ; //Fondation Universit&#xe9; de Paris/ ; //AXA research fund/ ; //Fondation Hopitaux de Paris-Hopitaux de France/ ; //M&#xe9;c&#xe9;nat du GH APHP/ ; //CUP/ ; //Fondation for the research in Physiology and DMU BioPhyGen/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Aging/physiology ; *Cardiovascular Diseases/physiopathology ; Carotid-Femoral Pulse Wave Velocity ; *COVID-19/complications/physiopathology/epidemiology ; Prospective Studies ; Pulse Wave Analysis ; SARS-CoV-2 ; *Vascular Stiffness/physiology ; },
abstract = {BACKGROUND AND AIMS: Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through development of vascular damage. The study aimed to investigate whether accelerated vascular ageing occurs after COVID-19 infection, and if so, identify its determinants.<br><br>METHODS: This prospective, multicentric, cohort study, included 34 centres in 16 countries worldwide, in 4 groups of participants-COVID-19-negative controls (&#x2170;) and three groups of individuals with recent (6 &#xb1; 3 months) exposure to SARS-CoV-2: not hospitalized (&#x2171;), hospitalized in general wards (&#x2172;), and hospitalized in intensive care units (&#x2173;). The main outcome was carotid-femoral pulse wave velocity (PWV), an established biomarker of large artery stiffness.<br><br>RESULTS: 2390 individuals (age 50 &#xb1; 15 years, 49.2% women) were recruited. After adjustment for confounders, all COVID-19-positive groups showed higher PWV (+0.41, +0.37, and +0.40&#x2005;m/s for groups 2-4, P < .001, P = .001 and P = .003) vs. controls [PWV 7.53 (7.09; 7.97) m/s adjusted mean (95% CI)]. In sex-stratified analyses, PWV differences were significant in women [PWV (+0.55, +0.60, and +1.09&#x2005;m/s for groups 2-4, P < .001 for all)], but not in men. Among COVID-19 positive women, persistent symptoms were associated with higher PWV, regardless of disease severity and cardiovascular confounders [adjusted PWV 7.52 (95% CI 7.09; 7.96) vs. 7.13 (95% CI 6.67; 7.59) m/s, P < .001]. A stable or improved PWV after 12 months was found in the COVID+ groups, whereas a progression was observed in the COVID- group.<br><br>CONCLUSIONS: COVID-19 is associated with early vascular ageing in the long term, especially in women.},
}
@article {pmid40819231,
year = {2025},
author = {Levin, J and Bradshaw, M},
title = {The Challenge of Long COVID: Is the Pandemic Really Over?.},
journal = {Public health reports (Washington, D.C. : 1974)},
volume = {140},
number = {5-6},
pages = {506-513},
pmid = {40819231},
issn = {1468-2877},
mesh = {Humans ; *COVID-19/epidemiology/complications ; United States/epidemiology ; SARS-CoV-2 ; Prevalence ; Public Health ; Pandemics ; Post-Acute COVID-19 Syndrome ; Incidence ; },
abstract = {Sequelae of SARS-CoV-2 infection began appearing among patients who had COVID-19 within months of the first wave of the COVID-19 pandemic in 2020. This phenomenon, termed post-COVID-19 condition and also known as long COVID, has been a source of controversy among physicians, as presentation of long COVID has been a somewhat mysterious constellation of signs and symptoms that seem mostly impervious to efficacious treatment. Although a considerable amount has been learned about the pathophysiology and other biomedical features of long COVID, the epidemiologic parameters of long COVID, including incidence and prevalence, are uncertain in the United States and globally. The best estimates are that millions of people have long COVID. Despite the declining incidence of COVID-19, the low case fatality of long COVID suggests that its prevalence is poised to continue to grow. This increasing prevalence of long COVID presents a challenge for the public health sector. Here, we examine the public health implications of long COVID. We offer policy recommendations, including ending congratulatory talk that the pandemic is over, encouraging more focused attention from the United States and global nongovernmental organizations, and establishing a multinational research initiative to better understand and respond to long COVID and other postviral and postinfectious chronic conditions. Although COVID-19 may not be as widespread and disruptive as in the early months of the pandemic, it would be a mistake to presume that, because the acute crisis is behind us, the pandemic is past. Long COVID is an ongoing public health threat and merits our concern.},
}
@article {pmid40818641,
year = {2025},
author = {Barrero-Santiago, L and Bellosta-López, P and Doménech-García, V and Pérez-Pérez, L and Tellería, JJ and Almansa, R and Montero-Cuadrado, F},
title = {Determinants of quality of life in long-COVID patients with new-onset chronic pain.},
journal = {The journal of pain},
volume = {35},
number = {},
pages = {105531},
doi = {10.1016/j.jpain.2025.105531},
pmid = {40818641},
issn = {1528-8447},
mesh = {Humans ; *Quality of Life/psychology ; Female ; *Chronic Pain/psychology/etiology/physiopathology ; Male ; Middle Aged ; *COVID-19/complications/psychology ; Case-Control Studies ; Adult ; Anxiety/psychology ; },
abstract = {Chronic pain is highly prevalent in Long-COVID syndrome and significantly impacts quality of life (QoL). Given the complexity of long-COVID, a comprehensive approach is necessary to understand how the interactions of psychosocial, pain and functional factors may influence patients' well-being. This study aimed to explore key factors associated with QoL in long-COVID patients with new-onset chronic pain, and to multidimensionally characterize this population. A case-control design was used, recruiting 163 Long-COVID patients (49.04±8.23 years, 80% females) and 151 controls (48.86±8.28 years, 78% females). Socio-demographic, psychosocial, pain-related and functional outcomes were measured. QoL, assessed by the EQ-5D, was considered the main outcome. Anxiety was negatively associated with QoL (β=-0.012,95%CI:[-0.015, -0.008],p<0.001), while aerobic capacity showed a positive association (β=0.001,95%CI:[0.001,0.002],p<0.001). Employment status (β=0.175,95%CI:[0.091,0.260],p<0.001), pain intensity (β=-0.003,95%CI:[-0.005,-0.001],p=0.004) and symptom complexity (β=-0.32,95%CI:[-0.51,-0.13],p<0.001) were also significant associated factors. The strongest factor associated with being a case was higher levels of symptoms complexity (OR=1.09;95%CI:[1.05, 1.15];p<0.001) followed by higher levels of depression (OR=1.13; 95%CI:[1.04,1.22];p=0.002). Long-COVID patients reported poorer self-perceived QoL and had significantly lower overall QoL, as well as worse outcomes in functional, pain-related and psychosocial variables when compared to control subjects (p<0.001). Clinicians should pay attention to anxiety levels, aerobic capacity, work status and pain intensity early in the course of the disease to try to minimize the loss of QoL in this population. These findings may also assist clinicians in profiling their patients and guiding them toward an early and target ed intervention that addresses the associated factors, ultimately improving functionality and QoL of patients. PERSPECTIVE: This study identifies key clinical and psychosocial factors linked to new-onset chronic pain and reduced quality of life in long-COVID. Understanding these insights may help clinicians implement early, targeted, and interdisciplinary interventions to improve patient functionality and long-term outcomes.},
}
@article {pmid40810942,
year = {2025},
author = {Gunturkun, F and Hedlin, H and Botzheim, B and Deng, Y and Bonilla, H and Jagannathan, P and Quach, TC and Kim, S and Lin, M and O'Riordan, G and Tzeng, H and Adamowicz, L and Demanuele, C and Cai, X and Yang, PC and Singh, U and Geng, LN},
title = {Digital Biometric Measures in Long COVID: A Secondary Analysis of the STOP-PASC Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {8},
number = {8},
pages = {e2526901},
pmid = {40810942},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; SARS-CoV-2 ; *Ritonavir/therapeutic use/administration &amp; dosage ; *Biometry/methods ; Adult ; *Wearable Electronic Devices ; *COVID-19 Drug Treatment ; },
abstract = {IMPORTANCE: Digital biometrics can be used to monitor disease, but there is limited research on their applications for assessing postacute sequelae of SARS-CoV-2 (PASC) or long COVID.<br><br>OBJECTIVE: To better understand digital biometric patterns in long COVID using wearable device technology and whether there are any differences between the nirmatrelvir-ritonavir and placebo-ritonavir intervention arms.<br><br>This secondary analysis is an exploratory substudy of a placebo-controlled randomized clinical trial (Selective Trial of Paxlovid for PASC [STOP-PASC]) that was conducted from November 2022 to September 2023 at Stanford University. Trial participants were randomized, and a subset enrolled into the prespecified substudy.<br><br>INTERVENTION: Participants were randomized 2:1 to receive oral nirmatrelvir (300 mg) and ritonavir (100 mg) or placebo-ritonavir twice daily for 15 days. Substudy participants were provided with a smartwatch and asked to wear it for 24 hours a day, 7 days a week for the 15-week study.<br><br>MAIN OUTCOMES AND MEASURES: Mean changes in digital biometric measures in physical activity, heart rate, and oxygen saturation tracked by a smartwatch. Biometric measures were summarized by treatment arm for each of 5 different time frames: baseline, treatment period, and 3 subsequent time intervals. Summary measure trajectories were clustered and demographics and clinical characteristics were compared among clusters using absolute standardized differences expressed in units of SDs.<br><br>RESULTS: Of the 94 participants enrolled in the substudy, 50 (37 in nirmatrelvir-ritonavir and 13 in placebo-ritonavir) met the analysis eligibility criteria based on wear time and data completeness. These participants had a mean (SD) age of 42.7 (13.2) years and included 29 females (58.0%). Using mixed models for repeated measures, no significant differences were detected between the intervention arms in the change in biometric measures over time, consistent with the patient-reported outcomes in the STOP-PASC trial. In the overall substudy cohort, latent class mixed models and cluster analysis identified distinct longitudinal trajectories of long COVID over the 15-week study that tracked with different symptoms. Participants with lower daytime physical activity reported more severe fatigue (9 of 9 [100%] vs 21 of 23 [91.3%]; absolute standardized difference [ASD], 0.30), shortness of breath (9 of 9 [100%] vs 7 of 23 [30.4%]; ASD, 1.31), and cardiovascular symptoms (8 of 9 [88.9%] vs 12 of 23 [52.2%]; ASD, 0.70). Those with higher nighttime physical activity reported more gastrointestinal symptoms (2 of 3 [66.7%] vs 11 of 35 [31.4%]; ASD, 0.50). Additionally, participants with higher median daytime heart rates reported less fatigue (7 of 9 [77.8%] vs 39 of 40 [97.5%]; ASD, 0.63) and shortness of breath (3 of 9 [33.3%] vs 23 of 40 [57.5%]; ASD, 0.50) compared with those with lower heart rates.<br><br>CONCLUSIONS AND RELEVANCE: This secondary analysis identified distinct longitudinal trajectories of physiological and behavioral digital biometric measures captured from wearable devices that reflect the heterogeneity and track with different symptoms of long COVID. Digital biometric measures from wearable devices have promising utility for long COVID research.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05576662.},
}
@article {pmid40809128,
year = {2024},
author = {Sun, J and Aikawa, M and Ashktorab, H and Beckmann, ND and Enger, ML and Espinosa, JM and Gai, X and Horne, BD and Keim, P and Lasky-Su, J and Letts, R and Maier, CL and Mandal, M and Nichols, L and Roan, NR and Russell, MW and Rutter, J and Saade, GR and Sharma, K and Shiau, S and Thibodeau, SN and Yang, S and Miele, L and , },
title = {A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions.},
journal = {Frontiers in systems biology},
volume = {4},
number = {},
pages = {1422384},
pmid = {40809128},
issn = {2674-0702},
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC or "Long COVID"), includes numerous chronic conditions associated with widespread morbidity and rising healthcare costs. PASC has highly variable clinical presentations, and likely includes multiple molecular subtypes, but it remains poorly understood from a molecular and mechanistic standpoint. This hampers the development of rationally targeted therapeutic strategies. The NIH-sponsored "Researching COVID to Enhance Recovery" (RECOVER) initiative includes several retrospective/prospective observational cohort studies enrolling adult, pregnant adult and pediatric patients respectively. RECOVER formed an "OMICS" multidisciplinary task force, including clinicians, pathologists, laboratory scientists and data scientists, charged with developing recommendations to apply cutting-edge system biology technologies to achieve the goals of RECOVER. The task force met biweekly over 14 months, to evaluate published evidence, examine the possible contribution of each "omics" technique to the study of PASC and develop study design recommendations. The OMICS task force recommended an integrated, longitudinal, simultaneous systems biology study of participant biospecimens on the entire RECOVER cohorts through centralized laboratories, as opposed to multiple smaller studies using one or few analytical techniques. The resulting multi-dimensional molecular dataset should be correlated with the deep clinical phenotyping performed through RECOVER, as well as with information on demographics, comorbidities, social determinants of health, the exposome and lifestyle factors that may contribute to the clinical presentations of PASC. This approach will minimize lab-to-lab technical variability, maximize sample size for class discovery, and enable the incorporation of as many relevant variables as possible into statistical models. Many of our recommendations have already been considered by the NIH through the peer-review process, resulting in the creation of a systems biology panel that is currently designing the studies we proposed. This system biology strategy, coupled with modern data science approaches, will dramatically improve our prospects for accurate disease subtype identification, biomarker discovery and therapeutic target identification for precision treatment. The resulting dataset should be made available to the scientific community for secondary analyses. Analogous system biology approaches should be built into the study designs of large observational studies whenever possible.},
}
@article {pmid40808967,
year = {2025},
author = {Tan, C and Meng, J and Dai, X and He, B and Liu, P and Wu, Y and Xiong, Y and Yin, H and Wang, S and Gao, S},
title = {Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials.},
journal = {EClinicalMedicine},
volume = {87},
number = {},
pages = {103412},
pmid = {40808967},
issn = {2589-5370},
abstract = {BACKGROUND: Long COVID, characterized by persistent multi-organ symptoms post-SARS-CoV-2 infection, poses a substantial global health burden. While diverse therapeutic interventions have been proposed, their comparative efficacy remains uncertain due to fragmented evidence and methodological heterogeneity in prior studies. Therefore, we conducted a meta-analysis to comprehensively explore the effectiveness of diverse therapeutic interventions in long COVID.<br><br>METHODS: In this meta-analysis, we searched PubMed, Cochrane Library, Embase, Web of Science, SPORTDiscus (EBSCO), CINAHL (EBSCO), and Rehabilitation &amp; Sports medicine source (EBSCO) from inception to July 20, 2025, for randomized controlled trials (RCTs) evaluating exercise training, respiratory muscle training, telerehabilitation, transcranial direct current stimulation (tDCS), olfactory training, palmitoylethanolamide with luteolin (PEA-LUT), and steroid sprays in adults with Long COVID. Primary outcomes included cardiopulmonary function, exercise capacity, fatigue, and olfactory recovery. Data were pooled using random-effects models, with sensitivity analyses (leave-one-out method) and Egger's test to assess robustness and publication bias. GRADE criteria evaluated evidence certainty. The study was registered with PROSPERO (CRD42024591704).<br><br>FINDINGS: We identified a total of 51 eligible trials, comprising 4026 participants. Significant differences were observed in the following outcomes in the context of exercise training: 6MWT (MD, 83.20; 95% CI 52.04-114.37), 30sSTS (MD, 3.05; 95% CI 1.96-4.13), SF-12 Mental Component Summary (SF-12-MCS) (MD, 3.10; 95% CI 0.78-5.43), VO2 peak (% predicted) (MD, 6.00; 95% CI 0.45-11.54), VO2 peak (L/kg/min) (MD, 1.61; 95% CI 0.40-2.81), VO2 peak (L/min) (MD, 0.14; 95% CI 0.03-0.25), mMRC dyspnea scale (MD, -1.04; 95% CI -1.73 to -0.35), the Multidimensional Functional Assessment of Daily Living Scale (MBDS) (MD, -4.61; 95% CI -8.19 to -1.03), and Visual Analogue Fatigue Scale (VAFS) (MD -1.69; 95% CI -3.07 to -0.31). Furthermore, significant differences were also found in the following key outcomes: 6MWT (MD, 89.54; 95% CI 9.86-169.23), MIP (% predicted) (MD, 15.79; 95% CI 2.73-28.84), MIP (cm H2O) (MD, 19.69; 95% CI 10.14-29.24), and mMRC (MD, -1.02; 95% CI -1.86 to -0.18) in respiratory muscle training; 6MWT (MD 34.14; 95% CI 2.54-65.74), 30sSTS (MD 1.41; 95% CI 0.67-2.15), and FSS (MD -1.59; 95% CI -2.64 to -0.53) in telerehabilitation; MFIS-physical (MD, -2.29; 95% CI -4.36 to -0.22) in tDCS; and TDI Score (MD, 4.66; 95% CI 2.16-7.15) in PEA-LUT.<br><br>INTERPRETATION: Exercise training should be prioritized for improving cardiopulmonary function and exercise capacity in Long COVID, supported by high-certainty evidence. Respiratory muscle training and PEA-LUT offer targeted benefits for respiratory strength and anosmia, while tDCS may address fatigue. Telerehabilitation, as a form of supervision, also improved the effectiveness of the intervention. In contrast, steroid sprays and olfactory training lack efficacy, highlighting the need for personalized, symptom-specific approaches. These findings advocate for updated clinical guidelines integrating multimodal therapies and underscore the urgency of large-scale trials to optimize dosing and long-term outcomes.<br><br>FUNDING: This study was supported by the Hunan Provincial Natural Foundation of China (2021JJ30040), the National Key Research and Development Plan (2022YFC3601900, 2022YFC2505500), the National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University (2021KFJJ06), and the National Natural Science Foundation of China (No. 81672225).},
}
@article {pmid40808898,
year = {2025},
author = {Townsend, L and Domegan, L and Wang, W and Quirke, S and , and Bergin, C and Fleming, C},
title = {Factors influencing healthcare worker symptomatic respiratory infection and vaccine uptake during the post-COVID-19 pandemic period.},
journal = {Antimicrobial stewardship &amp; healthcare epidemiology : ASHE},
volume = {5},
number = {1},
pages = {e183},
pmid = {40808898},
issn = {2732-494X},
abstract = {OBJECTIVE: Investigate the factors associated with symptomatic respiratory infection and uptake of seasonal SARS-CoV-2 and influenza vaccine amongst healthcare workers (HCWs).<br><br>DESIGN: Longitudinal prospective multi-center study.<br><br>SETTING: Two tertiary healthcare centers in Ireland.<br><br>PARTICIPANTS: N = 893 self-selected HCWs across all disciplines.<br><br>METHODS: Monthly self-reported questionnaires from September 2024 to February 2025 completed by all participants, providing infection symptoms, self-testing for COVID-19 and receipt of vaccination against SARS-CoV-2 or influenza in the preceding 30 days. Additional data collected included comorbidities, known diagnosis of Long COVID, demographic data, prior infection and vaccination status, and healthcare role. Multivariable logistic regression models assessed the factors associated with symptom development, self-testing, and vaccine uptake.<br><br>RESULTS: Symptomatic respiratory illness was reported by n = 321 (36%) of participants during the study period, with a preexisting diagnosis of Long COVID associated with developing symptoms. Testing for COVID-19 was performed by 63% (n = 202) of symptomatic individuals, with a shorter duration since prior infection the only significant predictor of self-testing. Vaccine uptake was variable, with 37% receiving influenza and 22% receiving SARS-CoV-2 vaccination for that period. Older age and shorter interval since previous vaccine were associated with increased uptake of both vaccines, while men were more likely to be vaccinated against COVID-19.<br><br>CONCLUSIONS: In the postpandemic period, self-reported symptomatic respiratory infections remain common amongst HCWs. The legacy of the pandemic influences this, with a preexisting diagnosis of Long COVID associated with increased symptom burden, while low vaccination rates and understanding the factors associated with this present a challenge to ongoing risk mitigation.},
}
@article {pmid40806985,
year = {2025},
author = {Cossu, G and Kalcev, G and Primavera, D and Lorrai, S and Perra, A and Galetti, A and Demontis, R and Tramontano, E and Bert, F and Montisci, R and Maleci, A and Castilla, PJF and Jaramillo, SG and Kurotschka, PK and Rocha, NB and Carta, MG},
title = {The Use of Heart Rate Variability-Biofeedback (HRV-BF) as an Adjunctive Intervention in Chronic Fatigue Syndrome (CSF/ME) in Long COVID: Results of a Phase II Controlled Feasibility Trial.},
journal = {Journal of clinical medicine},
volume = {14},
number = {15},
pages = {},
pmid = {40806985},
issn = {2077-0383},
support = {PNRR-PE13 INF-ACT//PNRR-PE13 INF-ACT "One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases PE00000007/ ; //Fondazione di Sardegna, Bando Salute Pubblica, Medicina Preventiva e Riabilitativa, 2022/ ; },
abstract = {Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p < 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID.},
}
@article {pmid40806391,
year = {2025},
author = {Korobova, ZR and Arsentieva, NA and Butenko, AA and Kudryavtsev, IV and Rubinstein, AA and Turenko, AS and Ostankova, YV and Boeva, EV and Knizhnikova, AA and Norka, AO and Rassokhin, VV and Belyakov, NA and Totolian, AA},
title = {T Cell Dynamics in COVID-19, Long COVID and Successful Recovery.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806391},
issn = {1422-0067},
support = {#225011700915-1//State Task/ ; },
mesh = {Humans ; *COVID-19/immunology/pathology ; Male ; Middle Aged ; Female ; *SARS-CoV-2/immunology ; Adult ; Aged ; Immunologic Memory ; CD8-Positive T-Lymphocytes/immunology ; *T-Lymphocyte Subsets/immunology ; },
abstract = {Despite targeting mainly the respiratory tract, SARS-CoV-2 disrupts T cell homeostasis in ways that may explain both acute lethality and long-term immunological consequences. In this study, we aimed to evaluate the T-cell-mediated chain of immunity and formation of TCR via TREC assessment in COVID-19 and long COVID (LC). For this study, we collected 231 blood samples taken from patients with acute COVID-19 (n = 71), convalescents (n = 51), people diagnosed with LC (n = 63), and healthy volunteers (n = 46). With flow cytometry, we assessed levels of CD4+ and CD8+ minor T cell subpopulations (i.e., naïve, central and effector memory cells (CM and EM), Th1, Th2, Th17, Tfh, Tc1, Tc2, Tc17, Tc17.1, and subpopulations of effector cells (pE1, pE2, effector cells)). Additionally, we measured TREC levels. We found distinct changes in immune cell distribution-whilst distribution of major subpopulations of T cells was similar between cohorts, we noted that COVID-19 was associated with a decrease in naïve Th and CTLs, an increase in Th2/Tc2 lymphocyte polarization, an increase in CM cells, and a decrease in effector memory cells 1,3, and TEMRA cells. LC was associated with naïve CTL increase, polarization towards Th2 population, and a decrease in Tc1, Tc2, Em2, 3, 4 cells. We also noted TREC correlating with naïve cells subpopulations. Our findings suggest ongoing immune dysregulation, possibly driven by persistent antigen exposure or tissue migration of effector cells. The positive correlation between TREC levels and naïve T cells in LC patients points to residual thymic activity. The observed Th2/Th17 bias supports the hypothesis that LC involves autoimmune mechanisms, potentially driven by molecular mimicry or loss of immune tolerance.},
}
@article {pmid41383902,
year = {2023},
author = {Mendoza-Portillo, E and Aleman-Navarro, E and Prieto, GA and Rosenstein, Y and Lozano-Nuevo, JJ and Perez-Lopez, A},
title = {Neurological manifestations with jugular vein thrombosis linked to an inflammatory profile may be a sequela of long COVID.},
journal = {Neuroprotection (Chichester, England)},
volume = {1},
number = {2},
pages = {170-175},
pmid = {41383902},
issn = {2770-730X},
abstract = {More than 670 million cases of coronavirus disease 2019 (COVID-19) have been recorded worldwide in the 3 years since the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. About 45% of survivors of COVID-19 develop a syndrome known as long-term COVID, in which symptoms persist even months after the acute infection. About 76% of patients with long COVID experience neurological manifestations. Moreover, patients who have survived COVID-19 have an increased risk of cerebral venous thrombosis. This case report describes a 41-year-old woman who developed neurological manifestations associated with jugular vein thrombosis 24 h after administration of the Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine (AstraZeneca-Serum Institute of India). She had been infected with SARS-CoV-2 three months before vaccination. Although initially suspected to be a case of vaccine-induced immune thrombotic thrombocytopenia (VITT) in view of her recent vaccination, the patient did not have any hallmarks of VITT, such as thrombocytopenia, an increased d-dimer level, or antibodies against platelet factor-4. Moreover, the neurological manifestations were associated with a high concentration of inflammatory cytokines, including interleukin (IL)-6, IL-17A, and IL-21, and elevated neutrophil levels in cerebrospinal fluid, suggesting that inflammatory immune components had a role in the development of thrombotic events and pointing to an alternative diagnosis. In this case, the laboratory results indicated that the neurological manifestations associated with jugular vein thrombosis were not associated with VITT. Therefore, we propose that the thrombosis of the left jugular vein was a sequela of SARS-CoV-2 infection.},
}
@article {pmid41583965,
year = {2023},
author = {Lee, H and Seo, Y and Kim, J and Song, HY and Park, J and Yang, Y},
title = {The impact of Long COVID, work stress related to infectious diseases, fatigue, and coping on burnout among care providers in nursing home: A cross-sectional correlation study.},
journal = {Journal of Korean gerontological nursing},
volume = {25},
number = {3},
pages = {271-283},
pmid = {41583965},
issn = {2383-8086},
abstract = {PURPOSE: An increasing number of nursing home are being established because of the increased demand for treatment and care of older adults with chronic diseases related to population aging. This study aimed to examine the impact of long COVID, infectious diseases-related to work stress, fatigue, and coping on burnout among care providers in nursing home during the persistent COVID-19 pandemic.<br><br>METHODS: A total of 168 care providers, including nurses, nursing assistants, and caregivers working in nursing home between July 22 and August 12, 2022 were polled by a questionnaire survey. The collected data were analyzed using an independent t-test, one-way analysis of variance, Scheff&#xe9; test, Pearson correlation coefficient, and multiple regression analyses via SPSS 21.0.<br><br>RESULTS: The prevalence of Long COVID-19 among care providers in nursing home was 85.7%, with a mean burnout score of 2.59 out of 5. Work stress related to infectious diseases (&#x3b2;=.27, p=.002) and infection control fatigue (e.g., fatigue related to complexity of nursing duties and shortage in employees [&#x3b2;=.51, p=.019], conflicts caused by uncertain situations and a lack of support [&#x3b2;=.50, p=.012]) were the variables that significantly associated with burnout.<br><br>CONCLUSION: It is crucial to actively explore strategies for reducing overall work stress, anxiety, and fatigue, particularly related to infection management to alleviate burnout among care providers in nursing home. Our findings provide fundamental data for the development of interventions and policies to prevent care providers' burnout, thus enabling the provision of high-quality care in nursing home.},
}
@article {pmid41426470,
year = {2023},
author = {Castellanos, PL and Satashia, P and Punj, M and Castillo, PR and Colaco, BM and Dredla, BK and Festic, E and Kaplan, J and Ruoff, CM and Speicher, LL and Walsh, KL and Werninck, N and Yin, M and Burger, CD and Arunthari, V and Cheung, J},
title = {Assessment of sleep quality and sleep disordered breathing among post-hospitalized patients with COVID-19.},
journal = {Frontiers in sleep},
volume = {2},
number = {},
pages = {1214036},
pmid = {41426470},
issn = {2813-2890},
abstract = {BACKGROUND AND OBJECTIVES: We conducted a cross-sectional study to identify the presence of sleep disturbance and sleep disordered breathing in post-hospitalized patients with COVID-19 compared to a cohort of patients with no prior COVID-19 infection.<br><br>METHODS: Patients who were discharged from Mayo Clinic after hospitalization for COVID-19 and who had no existing diagnosis of sleep apnea or other sleep disorders were recruited for this study as cases. Patients who never had COVID-19 infection, nor any existing diagnosis of sleep apnea or other sleep disorders, were recruited from outpatient clinics as controls. Participants completed Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Fatigue Severity Scale questionnaires, as well as a home sleep apnea test.<br><br>RESULTS: Forty-seven COVID-19 cases and 46 controls completed questionnaires. Cases were significantly older, with a median age of 56.0 vs. controls (50.5) and were found to have slightly worse sleep quality, a higher degree of daytime sleepiness, and a slightly higher degree of fatigue. In terms of sleep disordered breathing, 39 cases and 40 controls completed the home sleep apnea test. Obstructive sleep apnea, defined by an AHI score of 5 or higher, was found in a remarkable 97.4% of cases vs. 72.5% in controls. Severity of OSA also trended higher in the case group. However, the difference in AHI was not significant after adjusting for age and BMI.<br><br>CONCLUSION: Patients who were hospitalized with COVID-19 showed a very high prevalence of OSA. In addition, they had a slightly higher degree of sleep disturbance, daytime sleepiness, and fatigue when compared to controls. Our results suggest that sleep medicine assessment in patients who had COVID-19 requiring hospitalization is warranted.},
}
@article {pmid40957051,
year = {2023},
author = {Vu, PD and Bansal, V and Lin, MJ and Bruel, B},
title = {Sphenopalatine Ganglion Block for Postacute Sequelae SARS-CoV-2 Infection Headaches: A Case Report and Review of the Literature.},
journal = {Pain medicine case reports},
volume = {7},
number = {3},
pages = {157-161},
pmid = {40957051},
issn = {2768-5152},
abstract = {BACKGROUND: In a subset of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), neurological symptoms including "brain fog" and headache persist beyond the acute phase of the infection, often referred to as postacute sequelae SARS-CoV-2 infection (PASC), or Long COVID. Current practice supports a multi-modal approach to address PASC symptoms. One technique for chronic headaches not utilized for PASC is sphenopalatine ganglion blocks (SPGB). We evaluate the pathophysiology of PASC headaches, review the utilization of sphenopalatine ganglion blocks in primary headaches, and discuss the potential for SPGB in PASC headaches.<br><br>CASE REPORT: We present a patient with PASC headaches who failed various conservative and interventional therapies. Worsening symptoms resulted in pursuing bilateral SPGB, resulting in an 80% improvement in symptoms. To our knowledge, we report the first PASC headache treated with an SPGB via infrazygomatic injection.<br><br>CONCLUSION: SPGB can treat PASC headaches and improve a patient's quality of life.},
}
@article {pmid40957038,
year = {2023},
author = {Uhlenhopp, R and Taylor, C and Tomlinson, H and McManus, M and Burke, MD},
title = {Alleviation of COVID-19 Parosmia with Stellate Ganglion Block: A Case Report.},
journal = {Pain medicine case reports},
volume = {7},
number = {3},
pages = {101-104},
pmid = {40957038},
issn = {2768-5152},
abstract = {BACKGROUND: An estimated 23 million people in the United States are affected with Long COVID, formally called Postacute Sequelae SARS-CoV-2 infection (PASC). Disturbances of taste and smell are common symptoms. There is limited evidence for effective treatment.<br><br>CASE REPORT: A 68-year-old woman contracted COVID-19 in January 2021. She had worsening parosmia and dysgeusia, described as "rancid" smells with a variety of foods and objects. She underwent successful right stellate ganglion block in April 2022. Immediately after the procedure, she was able to comfortably eat food previously intolerable. Benefits persisted at 5- and 30-day follow-up.<br><br>CONCLUSIONS: An ever-expanding patient population and lack of treatment options emphasize the importance of continued research into the pathogenesis and treatment of PASC. A nascent body of evidence suggests stellate ganglion block may provide durable relief.},
}
@article {pmid40960332,
year = {2023},
author = {Kim, S and Hillery, T and Suric, V and Kim, C},
title = {Stellate Ganglion Block for Refractory Post-COVID Headache: Case Report.},
journal = {Pain medicine case reports},
volume = {7},
number = {2},
pages = {73-76},
pmid = {40960332},
issn = {2768-5152},
abstract = {BACKGROUND: Long coronavirus disease (COVID) is a multitude of symptoms weeks to months after recovering from COVID 2019 (COVID-19) and involves a variety of symptoms, ranging from brain fog and fatigue to refractory headaches that may result in ongoing disability.<br><br>CASE REPORT: A 49-year-old man presents for persistent headaches following COVID-19 infection months prior. The pain was frontal and bilateral but more prominent on the right, without sensitivity to light nor sound, and without identifiable triggers. He trialed numerous medications without relief. He rated his pain on average 8-10 on the Visual Analog Scale (VAS). After discussion of options, the patient elected to proceed with a stellate ganglion block (SGB). The patient underwent a right-sided SGB with 5 mL of 0.25% bupivacaine. Following the injection, the patient noted ~50% benefit immediately. On 6-week follow-up, he noted improvement of his headaches to 1-2 on the VAS. At 4 months, the headaches continued to be controlled (1-2 on the VAS).<br><br>CONCLUSIONS: Reports suggest that symptoms from long COVID are caused by dysregulation of the sympathetic nervous system. We report the use of the SGB for treating refractory headaches related to long COVID, suggesting that the SGB may relieve the dysautonomia.},
}
@article {pmid40960330,
year = {2023},
author = {Alnatour, OI and Wu, MM and Javed, S and Huh, BK},
title = {The Utilization of Stellate Ganglion Block in the Treatment of Long-COVID: A Case Series.},
journal = {Pain medicine case reports},
volume = {7},
number = {2},
pages = {63-68},
pmid = {40960330},
issn = {2768-5152},
abstract = {BACKGROUND: With the recent COVID-19 pandemic, chronic pain physicians undoubtedly face the challenge of treating long-COVID within the already complex chronic pain patient population. Sympathetic blockade of the stellate ganglion has historically been utilized as a diagnostic and therapeutic tool in confirming and targeting the sympathetically mediated component of many chronic pain conditions, but its role in treating long-COVID symptoms has yet to be thoroughly studied or elucidated.<br><br>CASE SERIES: We present a unique case series where the utilization of stellate ganglion blockade in one case and use of stellate ganglion blockade followed by rhizotomy in another were successful in sustained and near-complete relief of all initial long-COVID symptoms during a 3-month follow-up period.<br><br>CONCLUSIONS: Our case series presents promising results on the role of stellate ganglion blockade in the sustained and near-complete relief of multiple long-COVID symptoms during the longest known follow-up period to date.},
}
@article {pmid41496174,
year = {2023},
author = {Kearney, GD and Hylock, R and Park, YM and Jones, K and Wall, B and Howard, R and Iyer, P and Clay, M and Endres-Dighe, S and Stoner, MCD and Li, L and Cajka, J and Rhea, S},
title = {Regional Trends of COVID-19-Like Illness-Related Emergency Department Visits in North Carolina, March 1, 2020-November 30, 2020.},
journal = {North Carolina medical journal},
volume = {84},
number = {1},
pages = {54-60},
pmid = {41496174},
issn = {2379-4313},
abstract = {BACKGROUND: An evaluation of emergency department (ED) visits and the number of patients seeking care for COVID-19-like illness (CLI) during the initial phases of the SARS-CoV-2 (COVID-19) pandemic in North Carolina has not been exclusively described.<br><br>PURPOSE: To characterize CLI-related ED visits across North Carolina from March 1 to November 30, 2020.<br><br>METHODS: This was a retrospective, descriptive study. Data from the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT) and the US Census Bureau were used to calculate CLI-related ED visit rates for the North Carolina resident patient population, and to compare and describe regional trends (Eastern, Piedmont, and Western).<br><br>RESULTS: A total of 133,193 CLI-related ED visits were evaluated. Across the 3 regions, CLI-related ED visits followed similar trends with the highest peaks being reported in mid-July and late November 2020. The Piedmont region experienced the highest percent (56.3%), while people aged 25-49 years accounted for the largest age group (35.0 %) of CLI-related ED visits. More CLI-related ED visits occurred for White individuals (47.8%), but the Eastern region had a far higher percent (44.8%) of reported CLI-related ED visits for Black and American Indian individuals compared to the rest of the state.<br><br>LIMITATIONS: ICD-10-CM codes were not available during the early weeks of the pandemic, which limited the ability to evaluate CLI-related data during this time.<br><br>DISCUSSION: This evaluation summarizes regional trends of CLI-related ED visits across North Carolina during the first 9 months of the COVID-19 pandemic. These results provide useful information and insight for public health officials, health care administrators, and policymakers.},
}
@article {pmid40805931,
year = {2025},
author = {Mazzonetto, LF and Cordeiro, JFC and Correia, IM and Oliveira, AS and Moraes, C and Brilhadori, J and Gomide, EBG and Kudlacek, M and Machado, DRL and Anjos, JRCD and Santos, APD},
title = {Physical Training Protocols for Improving Dyspnea and Fatigue in Long COVID: A Systematic Review with Meta-Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {15},
pages = {},
pmid = {40805931},
issn = {2227-9032},
abstract = {Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings.},
}
@article {pmid40805888,
year = {2025},
author = {Liu, YH and Su, YH and Chang, SM and Chang, MY and Ma, WF},
title = {Association of Psychosocial and Health Factors with Long COVID Symptoms in Students in Medicine-Related Departments: A Cross-Sectional Survey.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {15},
pages = {},
pmid = {40805888},
issn = {2227-9032},
support = {CMR-114-113//China Medical University Hospital, Taiwan/ ; TCVGH-1127401E//Taichung Veterans General Hospital, Taiwan/ ; NSTC112-2813-C-039-165-B//National Science and Technology Council, Taiwan/ ; CMU111-MF-108//China Medical University, Taiwan/ ; },
abstract = {Background: As COVID-19 transitions to an endemic phase, long COVID symptoms remain a significant public health issue affecting both physical and mental health. A notable proportion of college students report symptoms such as fatigue, cough, and brain fog persisting for weeks or months post-infection. Objectives: This study explored the prevalence and contributing factors of long COVID symptoms among both infected and uninfected students in medicine-related departments. Methods: A cross-sectional study was conducted using online self-reported questionnaires completed by 1523 undergraduate and graduate students in medicine-related departments at a medical university. Participants who had tested positive for COVID-19 within the past three months were excluded. The survey assessed long COVID symptoms, with comparisons conducted between infected and uninfected groups. Multivariate logistic regression identified risk factors associated with long COVID symptoms. Results: Of the 1118 participants, 47.5% of those with a prior COVID-19 diagnosis reported long COVID symptoms within the past month. Significant differences between the infected and uninfected groups were observed in physical, cognitive, and psychological health. Logistic regression identified that prior COVID-19 diagnosis had an association with the presence of long COVID symptoms (odds ratio = 1.48, p = 0.024) after adjusted model analysis. Meanwhile, higher anxiety levels (odds ratio = 1.09, p < 0.001) and a BMI ≥ 24 (odds ratio = 4.50, p < 0.01) were identified as significant risk factors for post-infection syndrome among previously infected students. Sex and exercise habits also influenced symptom prevalence. Conclusions: Since late 2023, with those experiencing cumulative infections surpassing half of Taiwan's population, long COVID symptoms have persisted as a widespread concern affecting both physical and mental health, continuing into 2025. This study underscores critical risk factors and symptom patterns among students in medicine-related departments, reinforcing the urgency of sustained surveillance and targeted interventions to facilitate comprehensive recovery.},
}
@article {pmid40805835,
year = {2025},
author = {Lücker, P and Bahr, C and Kästner, A and Steinmetz, A and Rief, W},
title = {Development and Validation of the German Version of the Modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm).},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {15},
pages = {},
pmid = {40805835},
issn = {2227-9032},
support = {LAGuS/MV-6-SF915-0002/23//State of Mecklenburg - Western Pomerania, "MV-Schutzfonds"/ ; },
abstract = {Background: As a disease with a still largely unknown course, post-COVID requires a comprehensive multidimensional perspective and structured monitoring, as offered by the C19-YRSm. There has not yet been a German version of the scale. Methods: After the translation of the COVID-19 Yorkshire Rehabilitation Scale (modified version, C19-YRSm) into German, we conducted an online survey with it between 23 May 2023 and 10 May 2024 for patients with post-COVID condition. Participation took place twice; people received either only the German version or both the German and the original English versions of the scale at one-week intervals. Based on the results, reliability and validity of the German version of the C19-YRSm were extensively tested. Results: Data of 414 participants were analysed, 156 of whom took part twice at least seven days apart. Cronbach's alpha coefficients of the subscales of the German version ranged from 0.75 to 0.93. In the English version, it ranged from 0.82 to 0.93. All the subscales correlate with each other with p < 0.001. For the overall scale and for three of the four subscales, the intraclass coefficients, as a measure of the agreement between measurement results at two points in time, showed good consistency. Conclusions: This study confirmed the reliability, applicability, and clinical utility of the C19-YRSm, aligning with previous studies. With its multidimensional structure and excellent quality criteria, the C19-YRS is a valuable asset for clinical practice and research. The validated German C19-YRSm holds significant potential to facilitate tailored interventions, destigmatise post-COVID conditions, and enhance patient care in medical contexts.},
}
@article {pmid40804810,
year = {2025},
author = {Mehrotra-Varma, J and Henry, S and Chernoff, D and Galenchik-Chan, A and Duong, KS and Mehrotra-Varma, S and Wang, SH and Duong, TQ},
title = {Increased Incidence of New-Onset Diabetic Retinopathy in Individuals with COVID-19 in an Underserved Urban Population in the Bronx.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {15},
pages = {},
pmid = {40804810},
issn = {2075-4418},
abstract = {Background/Objectives: To investigate the incidence of new-onset diabetic retinopathy (DR) in individuals with pre-existing type 2 diabetes (T2D) up to 3 years post SARS-CoV-2 infection. Methods: This retrospective study consisted of 5151 COVID-19 and 5151 propensity-matched non-COVID-19 patients with T2D in the Montefiore Health System between 1 March 2020 and 17 January 2023. The primary outcome was new-onset DR at least 2 months after the index date up to 17 January 2023. Matching for index date between groups was also used to ensure the same follow-up duration. Hazard ratios (HRs) were computed, adjusted for competing risks. Results: T2D patients with COVID-19 had a higher cumulative incidence of DR than T2D patients. The unadjusted HR for COVID-19 status for developing new DR was 2.44 [1.60, 3.73], p < 0.001. The adjusted HR was 1.70 [1.08, 2.70], p < 0.05, and the adjusted HR for prior insulin use was 3.28 [2.10, 5.12], p < 0.001. Sex, ethnicity, and major comorbidities had no significant association with outcome. Conclusions: T2D patients who contracted COVID-19 exhibited a significantly higher risk of developing DR within three years post infection compared to propensity-matched controls. The increased incidence was primarily driven by greater pre-existing insulin usage and SARS-CoV-2 infection in the COVID-19 positive cohort.},
}
@article {pmid40804645,
year = {2025},
author = {Paval, NE and Căliman-Sturdza, OA and Lobiuc, A and Dimian, M and Sirbu, IO and Covasa, M},
title = {MicroRNAs in long COVID: roles, diagnostic biomarker potential and detection.},
journal = {Human genomics},
volume = {19},
number = {1},
pages = {90},
pmid = {40804645},
issn = {1479-7364},
support = {285/30.11.2022//Ministerul Cercet&#x103;rii, Inov&#x103;rii &#x15f;i Digitaliz&#x103;rii/ ; },
mesh = {Humans ; *COVID-19/genetics/diagnosis/virology ; *MicroRNAs/genetics ; Biomarkers/metabolism ; SARS-CoV-2 ; Sequence Analysis, RNA/methods ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), marked by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection, affects multiple organ systems including the respiratory, cardiovascular, neurological, gastrointestinal, and renal systems. These prolonged effects stem from chronic inflammation, immune dysregulation, and direct viral injury. MicroRNAs (miRNAs)-small non-coding RNAs involved in gene regulation-play a pivotal role in this process by modulating immune responses, inflammation, and cellular stress. Altered miRNA expression patterns during and after infection contribute to the pathogenesis of Long COVID. While conventional miRNA detection techniques have been valuable, they face limitations in sensitivity, throughput, and detecting RNA modifications. This review highlights Oxford Nanopore Sequencing (ONS) as a promising alternative, offering real-time, long-read, amplification-free RNA sequencing that preserves native modifications. ONS enables direct sequencing of full-length miRNAs and their precursors, providing novel insights into miRNA processing and regulatory roles. Despite current challenges with short-read accuracy, ongoing technical advances are improving ONS performance. Its integration in miRNA profiling holds significant potential for uncovering novel regulatory interactions and advancing clinical biomarker discovery in Long COVID and other conditions.},
}
@article {pmid40802983,
year = {2025},
author = {Antar, AAR and Peluso, MJ},
title = {CROI 2025: Acute and Postacute COVID-19.},
journal = {Topics in antiviral medicine},
volume = {33},
number = {3},
pages = {555-568},
pmid = {40802983},
issn = {2161-5853},
mesh = {Humans ; *COVID-19/prevention &amp; control ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; *Post-Exposure Prophylaxis ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Acute Disease ; Protease Inhibitors/therapeutic use ; },
abstract = {New research on acute and postacute COVID-19 was presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI). Results of the SCORPIO-PEP (Stopping COVID-19 Progression With Early Protease Inhibitor Treatment-Postexposure Prophylaxis) study indicated that the protease inhibitor ensitrelvir is effective for postexposure prophylaxis. Results from the second phaseof the Ubuntu study suggested that monovalent or bivalent booster doses of mRNA vaccines are equally protective in people with or without HIV. A phase II study of an inhaled broad-spectrum antiviral small interfering RNA showed faster clearance of virus and more rapid resolution of symptoms with its use. In addition, numerous studies improved our understanding of the long-term consequences of SARS-CoV-2 infection, including immunologic, metabolic, cardiovascular, neurologic, and other clinical sequelae. The application of new and more specific case definitions in research studies of long COVID provided new insights into the epidemiology and pathogenesis of this condition, although data on therapeutics from randomized clinical trials are still lacking.},
}
@article {pmid40802429,
year = {2025},
author = {Sevdimbaş, SH and İnal, AS and Kuşcu, F and Kurtaran, B and Candevir, A and Taşova, Y and Kömür, S},
title = {Follow-up evaluation of long COVID syndrome in patients with SARS-CoV-2 infection.},
journal = {Revista da Sociedade Brasileira de Medicina Tropical},
volume = {58},
number = {},
pages = {e00462025},
pmid = {40802429},
issn = {1678-9849},
mesh = {Humans ; Male ; *COVID-19/complications/physiopathology ; Female ; Quality of Life ; Adult ; Middle Aged ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Intensive Care Units ; Aged ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID, which refers to persistent symptoms following acute COVID-19, is being increasingly reported. However, available data regarding its prevalence and characteristics are limited. This study was conducted to evaluate the occurrence and presentation of long COVID in patients with COVID-19 who were followed up in outpatient, ward, or intensive care settings.<br><br>METHODS: This study included patients who were diagnosed with COVID-19 at least four weeks prior to the start of the study. The patients underwent symptom assessment at baseline and 1, 3, 6, and 12 months post-infection. Functional status was evaluated using the Post-COVID-19 Functional Status (PCFS) Scale, and quality of life was assessed using the SF-36 Health Survey questionnaire.<br><br>RESULTS: A total of 134 patients (71 males [54.2%]), with a mean age of 43.7 (15.3) years, participated in this study. The distribution of patients across care settings was as follows: 51.1% outpatients, 35.9% in wards, and 13% in intensive care units (ICUs). Fatigue during exertion was the most frequently reported long COVID symptom. Patients treated in ICUs experienced a higher burden of long COVID symptoms than those treated in outpatient or ward settings. Furthermore, patients treated in ICUs and wards had a significantly poorer quality of life and functional status than the outpatients.<br><br>CONCLUSIONS: Long COVID poses a significant ongoing health concern, particularly for patients who require intensive care during acute COVID-19. Vigilant monitoring of long-term sequelae, particularly those that affect quality of life and functional status, is crucial for individuals recovering from COVID-19.},
}
@article {pmid40802287,
year = {2025},
author = {Coughtrey, A and Pereira, SMP and Ladhani, S and Shafran, R and Stephenson, T},
title = {Long COVID in children and young people: then and now.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {5},
pages = {487-492},
pmid = {40802287},
issn = {1473-6527},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; Young Adult ; },
abstract = {PURPOSE OF REVIEW: On 11 March 2020, the WHO characterized COVID-19 as a pandemic. A clinical case definition for post-COVID-19 condition in children and adolescents by expert consensus was agreed by the WHO in 2023. It is now 5 years since the WHO declared a pandemic, and this review aims to summarize key advances in our understanding of long COVID over those 5 years.<br><br>RECENT FINDINGS: That symptoms could persist in adults and CYP for months after initial infection was first reported in Autumn 2020. Long COVID in adults is frequently characterized by symptoms of fatigue and breathlessness but brain-fog, joint and muscle pain have been reported much more commonly in adult follow-up than CYP. The most common persisting symptoms experienced by CYP after COVID-19 infection in initial studies, often with less than a year of follow-up, were fatigue, headache, shortness of breath and persisting loss of smell and taste. With longer follow-up, up to 2&#x200a;years, the commonest symptoms still include not only fatigue, headache and shortness of breath but also sleep difficulties, whereas loss of smell and taste persisted only in a minority. However, many symptoms were almost as common in test-negative controls, raising questions about the causal role of SARS-CoV-2 virus. Predictors of long COVID, as defined, were female sex, history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems.<br><br>SUMMARY: The implications of the findings for clinical practice and research are that long COVID is not the same in CYP as adults; both their physical and mental health should be studied; and intervention trials are needed.},
}
@article {pmid40802282,
year = {2025},
author = {Gerzanich, V and Zhang, C and Zhang, J and Sallapalli, BT and Pei, S and Nasr, M and Tosun, C and Zhang, Y and Tang, Q and Simard, JM and Zhao, RY},
title = {COVID-19-associated neuroinflammation and astrocyte death in the brain linked to ORF3a-induced activation of Sur1-mediated ion channels.},
journal = {mBio},
volume = {16},
number = {9},
pages = {e0201225},
pmid = {40802282},
issn = {2150-7511},
support = {G12MD007597/MD/NIMHD NIH HHS/United States ; R01NS102589, R01NS105633/NS/NINDS NIH HHS/United States ; R01 NS105633/NS/NINDS NIH HHS/United States ; I01 BX004652/BX/BLRD VA/United States ; I01BX004652//U.S. Department of Veterans Affairs/ ; R01NS107262/NS/NINDS NIH HHS/United States ; R01 NS107262/NS/NINDS NIH HHS/United States ; R01 NS102589/NS/NINDS NIH HHS/United States ; R21 AI175931/AI/NIAID NIH HHS/United States ; G12 MD007597/MD/NIMHD NIH HHS/United States ; R01 HL082517/HL/NHLBI NIH HHS/United States ; SC1 AI112785/AI/NIAID NIH HHS/United States ; R21AI175931//National Institute of Allergy and Infectious Diseases/ ; SC1AI112785//National Institute of Allergy and Infectious Diseases/ ; I01RX003060, I01BX004652//U.S. Department of Veterans Affairs/ ; I01 RX003060/RX/RRD VA/United States ; },
mesh = {Humans ; *Astrocytes/pathology/metabolism/virology ; *COVID-19/pathology/complications/metabolism/virology ; Animals ; SARS-CoV-2 ; *Viroporin Proteins/metabolism/genetics ; *Brain/pathology/virology/metabolism ; *Sulfonylurea Receptors/metabolism/genetics ; *Neuroinflammatory Diseases/virology/metabolism/pathology ; Mice ; Male ; *Ion Channels/metabolism ; Female ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected individuals with pre-existing medical conditions, such as neurocognitive disorders. Premorbid neurocognitive conditions compounded by COVID-19 can escalate into COVID-associated neurological complications, leading to severe illness or even death. As COVID-19 continues to persist and vaccines lose efficacy against emerging variants, individuals with neurocognitive disorders often experience prolonged symptoms that are further exacerbated by repeated breakthrough infections of highly diversified viral variants due to emergence of new viral mutations. Despite the significance of neurocognitive disorders as risk factors for COVID-19-related mortality and long COVID, the underlying causes remain largely unknown. In this study, we report a link between ORF3a expression and COVID-associated neuroinflammation and neurocytotoxicity in postmortem brain tissues from COVID-19 patients. These findings were further verified through neural cell-based in vitro and in vivo animal studies introducing ORF3a either alone or in the context of viral infection. As a membrane-associated protein, ORF3a induces upregulation of Sur1-regulated ion channels, resulting in intracellular Ca[2+] influx, apoptosis, and necrosis through both NF-kB-dependent and independent proinflammatory responses in astrocytes. These findings reveal a novel clinical and mechanistic link between ORF3a and Sur1-regulated ion channels, which are highly responsive to neuroinflammatory conditions causing neurodegeneration. Additionally, we have identified a Food and Drug Administration-approved drug, glibenclamide, and a natural antiviral compound glycyrrhizin that effectively mitigates the neuropathological effects of ORF3a, underscoring the therapeutic potential and clinical significance of these findings.IMPORTANCECoronavirus disease 2019 (COVID-19) disproportionately affects individuals with pre-existing neurocognitive conditions primarily due to COVID-19-associated neuroinflammation and neurotoxicity (CNN), which can progress to COVID-associated neurological disorders (CANDs), leading to severe illness and mortality. Despite CNN's significant contribution to CANDs and related morbidity and mortality, its underlying causes remain poorly understood. Our study identifies ORF3a as a key driver of CNN, establishing a direct clinical and functional link between ORF3a and CNN linking to CANDs. Mechanistically, ORF3a disrupts ion homeostasis in astrocytes by promoting Ca[2][+] influx through Sur1-regulated ion channels, contributing to CNN. Notably, the Food and Drug Administration-approved drug glibenclamide, a Sur1-specific inhibitor, and the natural compound glycyrrhizin effectively mitigate ORF3a-induced neuropathology, highlighting ORF3a as a promising therapeutic target. These findings present a potential strategy to eliminate CNN and prevent CANDs.},
}
@article {pmid40801614,
year = {2025},
author = {Sonkodi, B},
title = {Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection.},
journal = {Cells},
volume = {14},
number = {15},
pages = {},
pmid = {40801614},
issn = {2073-4409},
mesh = {Animals ; Humans ; *Channelopathies/metabolism ; *COVID-19/metabolism ; *Ion Channels/metabolism ; Neurons/metabolism/pathology ; Pandemics ; SARS-CoV-2 ; },
abstract = {The focal "hot spot" neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain-body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell-cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection.},
}
@article {pmid40801304,
year = {2025},
author = {Ellen, A},
title = {From Stagnation to Strategy: Challenges in Advancing Long COVID Research.},
journal = {Journal of evaluation in clinical practice},
volume = {31},
number = {5},
pages = {e70180},
pmid = {40801304},
issn = {1365-2753},
mesh = {Humans ; *COVID-19/physiopathology/complications/epidemiology/therapy ; *Biomedical Research/organization &amp; administration ; SARS-CoV-2 ; Comorbidity ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID is a debilitating multisystemic condition and is a major public health burden, yet the pathophysiology remains poorly understood and there are no effective treatments. Despite the urgent need for better management strategies, research into long COVID is losing momentum.<br><br>OBJECTIVES: To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field.<br><br>METHOD: The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward.<br><br>RESULTS: The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre-existing comorbidities. The absence of pre-infection baseline data further complicates the distinction between long COVID-specific pathophysiology and the effects of pre-existing co-morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings.<br><br>CONCLUSION: Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.},
}
@article {pmid40800841,
year = {2025},
author = {Reas, ET and Alderson-Myers, A and Solders, SK and Shen, Q and Rivera, CS and Wang, X and Stiver, J and Banks, SJ and Graves, JS},
title = {Long COVID-related blood-brain barrier breakdown and microstructure in older adults are modified by sex and Alzheimer's disease genetic risk.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {3},
number = {},
pages = {},
pmid = {40800841},
issn = {2837-6056},
abstract = {Long COVID is characterized by lingering symptoms following SARS-CoV-2 infection, which may include neurological and cognitive complaints. Hypothesized mechanisms, including blood-brain barrier (BBB) dysfunction and neuroinflammation, are shared with Alzheimer's disease (AD) and related dementias. To address concern that long COVID may accelerate cognitive decline and neurodegeneration, this study examined neuroimaging-based markers of BBB breakdown and brain microstructure among older adults with long COVID, and modification by AD risk factors. Individuals with persistent cognitive complaints following SARS-CoV-2 infection (neurological long COVID, NLCV) and cognitively normal controls (50-90 years, 61% women) underwent neuropsychological evaluation, genotyping, dynamic contrast-enhanced MRI to measure BBB permeability, and multi-compartment diffusion MRI to measure brain microstructure. Cognitive and brain measures were compared between NLCV and controls using analysis of covariance, and associations among measures were assessed using linear regression. Interaction models probed modification by sex and AD genetic risk, quantified with a polygenic hazard score. Compared to controls, NLCV exhibited cognitive impairment, BBB breakdown, and subcortical microstructural abnormalities. NLCV-related BBB leakage was widespread across the brain and more pronounced among men, whereas white matter and subcortical microstructural differences were stronger among women. AD polygenic hazard score modified associations of BBB permeability with memory and microstructure, such that higher caudate BBB permeability correlated with worse immediate recall, and higher white matter permeability correlated with higher free water only for those with elevated genetic risk. BBB dysfunction and microstructural compromise may contribute to cognitive symptoms of long COVID in older adults. Sex-specific patterns, and more deleterious associations between brain and memory abnormalities among individuals with elevated AD genetic risk, highlight the need for precision medicine diagnostic and therapeutic approaches for long COVID.},
}
@article {pmid40800146,
year = {2025},
author = {Maart, S and Hofmeyr, RA and Muller, JJ and Tserere, LB},
title = {A cross-sectional study on the long-term impact of COVID-19: Symptoms, disability and daily functioning.},
journal = {Health SA = SA Gesondheid},
volume = {30},
number = {},
pages = {2880},
pmid = {40800146},
issn = {2071-9736},
abstract = {BACKGROUND: Evidence suggests that survivors of coronavirus disease 2019 (COVID-19) experience ongoing symptoms, which is known as long COVID, or post-COVID syndrome. Approximately 100 million people globally are experiencing long COVID symptoms. Post-COVID syndrome (PCS) has debilitating effects on functioning and quality of life, potentially qualifying it as a disability.<br><br>AIM: This study aimed to assess the impact of PCS on disability levels using the WHO Disability Assessment Schedule (WHODAS 2.0).<br><br>SETTING: A digital cross-sectional survey was conducted through online platforms, including Facebook, WhatsApp, and Instagram.<br><br>METHODS: A self-developed questionnaire was distributed via social media to collect demographic information, COVID-19 symptoms, and severity. The WHODAS 2.0 instrument was used to measure disability levels. A total of 101 participants completed the online survey.<br><br>RESULTS: Most participants were aged between 21 years and 30 years (66%) and were female (60%). The most common acute COVID-19 symptoms were sore throat, fever, and headaches (84%). Post-COVID symptoms included brain fog and tiredness (82%). There was a statistically significant relationship between brain fog, depression, anxiety, and disability summary scores (p < 0.005). The mean WHODAS 2.0 score was 34%, indicating a moderate level of disability.<br><br>CONCLUSION: This study's results align with previous research, highlighting tiredness and neuropsychiatric symptoms as common among post-COVID patients. Post-COVID syndrome results in moderate disability when assessed using the WHODAS 2.0 with domains of Life Activities and Cognition mostly affected.<br><br>CONTRIBUTION: Post-COVID syndrome should be recognised as a disabling health condition, with rehabilitation prioritised as a critical intervention to enhance functional capacity and quality of life.},
}
@article {pmid40799952,
year = {2025},
author = {Di Micco, P and Siniscalchi, C and Imbalzano, E and Russo, V and Camporese, G and Lodigiani, C and Meschi, T and Perrella, A},
title = {COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.},
journal = {Infection and drug resistance},
volume = {18},
number = {},
pages = {3967-3975},
pmid = {40799952},
issn = {1178-6973},
abstract = {COVID-19, caused by SARS-CoV-2, has profoundly impacted global health since late 2019. Beyond respiratory complications, the disease involves systemic manifestations driven by immune dysregulation, inflammation, and coagulopathy. Among the many mechanisms implicated in severe disease, a growing body of evidence suggests a central role for the imbalance between proteases and antiproteases. This review examines how dysregulated protease activity contributes to viral entry, cytokine activation, vascular injury, and thrombosis. We focus on the integration of proteolytic systems such as the renin-angiotensin system, coagulation cascade, and neutrophil extracellular traps with established pathways like endothelial dysfunction and immune hyperactivation. Furthermore, we highlight therapeutic strategies aimed at restoring proteolytic balance and discuss the potential relevance of this paradigm in the management of long COVID.},
}
@article {pmid40796217,
year = {2025},
author = {},
title = {Correction to: Correlation of interferons and autoimmune aspects in long COVID-19 patients.},
journal = {International immunology},
volume = {37},
number = {10},
pages = {655-658},
doi = {10.1093/intimm/dxaf044},
pmid = {40796217},
issn = {1460-2377},
support = {COVID-19- K027083//Kawano Masanori Memorial Public Interest Incorporated Foundation/ ; },
}
@article {pmid40794410,
year = {2025},
author = {Gottlieb, M and Chen, J and Yu, H and Santangelo, M and Spatz, ES and Gentile, NL and Geyer, RE and Malicki, C and Gatling, K and O'Laughlin, KN and Stephens, KA and Elmore, JG and Wisk, LE and L'Hommedieu, M and Rodriguez, R and Montoy, JCC and Wang, RC and Rising, KL and Kean, E and Dyal, JW and Hill, MJ and Venkatesh, AK and Weinstein, RA and , },
title = {Work Impairment and Financial Outcomes Among Adults With vs Without Long COVID.},
journal = {JAMA network open},
volume = {8},
number = {8},
pages = {e2526310},
pmid = {40794410},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; *COVID-19/economics/epidemiology/psychology/complications ; Adult ; Middle Aged ; Prospective Studies ; Longitudinal Studies ; SARS-CoV-2 ; Quality of Life ; Efficiency ; Surveys and Questionnaires ; *Financial Stress ; },
abstract = {IMPORTANCE: While much of the focus on long COVID (LC; defined as developing new, persistent symptoms lasting 3 months or longer after SARS-CoV-2 infection) has been on health status and quality of life, the impact on individual work productivity and financial distress are less well established.<br><br>OBJECTIVES: To assess differences in work and financial outcomes among individuals with current, resolved, and no LC up to 3 years after initial infection.<br><br>This prospective, multisite, longitudinal cohort study enrolled adult participants (age &#x2265;18 years) with at least 1 reported SARS-CoV-2 infection from December 7, 2020, to August 29, 2022. Follow-up electronic surveys were collected through April 2, 2024. Data were analyzed from January 20 to February 4, 2025.<br><br>EXPOSURE: Self-reported resolved or current LC and vaccination status.<br><br>MAIN OUTCOMES AND MEASURES: Financial toxicity was measured using Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (FACIT-COST), and work impact was measured using the Work Productivity &amp; Activity Impairment questionnaire (version 2.0).<br><br>RESULTS: Of 3663 participants (mean [SD] age, 40.2 [14.2] years; 2429 [66.3%] female), 994 (27.1%) reported current LC, 2604 (71.1%) never had LC, and 65 (1.8%) had resolved LC. Participants with current LC reported more overall work impairment due to health (mean [SD], 17.7% [25.3%] of total hours worked per week) compared with those who never had LC (mean [SD], 3.2% [11.8%] of total hours) and resolved LC (mean [SD], 5.6% [12.2%] of total hours), with significantly increased odds of any work impairment compared with those who never had LC (adjusted odds ratio [aOR], 7.24; 95% CI, 5.68-9.21). The current LC group had increased odds of missing work due to their health (aOR, 2.62; 95% CI, 1.93-3.57) and of experiencing work impairment (aOR, 11.82; 95% CI, 8.90-15.70) compared with the group who never had LC. Individuals with current LC had increased odds of having moderate to high FACIT-COST scores compared with those who never had LC (aOR, 5.20; 95% CI, 3.92-6.89) and compared with those with resolved LC (aOR, 3.16; 95% CI, 1.19-8.41). Participants who were vaccinated had lower overall work impairment (aOR, 0.71; 95% CI, 0.55-0.92), impairment while working (aOR, 0.66; 95% CI, 0.50-0.87), impairment of nonwork activities (aOR, 0.74; 95% CI, 0.57-0.96), and financial toxicity (least-squares mean difference, 1.07; 95% CI, 0.19-1.95) compared with those who were not vaccinated.<br><br>CONCLUSIONS AND RELEVANCE: In this prospective cohort study of adults with SARS-CoV-2 infection, participants with current self-reported LC reported worse work impairment, missed work, and financial distress compared with those who never had LC, while vaccination was associated with improved work outcomes and less financial distress even among individuals with LC. These data underscore the need for postpandemic assistance programs, as well as vaccination to decrease societal harms.},
}
@article {pmid40794409,
year = {2025},
author = {Wisk, LE and L'Hommedieu, M and Diaz Roldan, K and Ebna Mannan, I and Spatz, ES and Weinstein, RA and Venkatesh, AK and Gottlieb, M and Huebinger, R and Rising, KL and Montoy, JCC and Stephens, KA and Rodriguez, RM and Hill, MJ and O'Laughlin, KN and Gentile, NL and Idris, AH and Li, SX and Santangelo, M and Kean, ER and McDonald, SA and Gatling, K and Elmore, JG and , },
title = {Variability in Long COVID Definitions and Validation of Published Prevalence Rates.},
journal = {JAMA network open},
volume = {8},
number = {8},
pages = {e2526506},
pmid = {40794409},
issn = {2574-3805},
mesh = {Humans ; Prevalence ; *COVID-19/epidemiology/diagnosis ; Female ; Middle Aged ; Male ; Adult ; Prospective Studies ; SARS-CoV-2 ; United States/epidemiology ; Aged ; Post-Acute COVID-19 Syndrome ; Young Adult ; Adolescent ; Registries ; Sensitivity and Specificity ; },
abstract = {IMPORTANCE: Long COVID definitions vary widely, and no consensus exists on how to accurately measure its prevalence, complicating both clinical care and research.<br><br>OBJECTIVE: To assess long COVID prevalence using various definitions from published literature.<br><br>This prospective, multicenter cohort study used data from the longitudinal Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE). Participants aged 18 years or older with symptoms suggestive of COVID-19 illness at the time of their index SARS-CoV-2 test enrolled at 8 sites across the US from December 11, 2020, through August 29, 2022, with follow-up surveys collected through February 28, 2023.<br><br>EXPOSURE: Positive or negative SARS-CoV-2 test result at the time of acute symptoms.<br><br>MAIN OUTCOMES AND MEASURES: Long COVID prevalence among INSPIRE participants with a positive vs negative index SARS-CoV-2 test, based on long COVID definitions in published literature. Secondary outcomes were sensitivity and specificity of published definitions compared with self-reported long COVID.<br><br>RESULTS: A total of 4575 INSPIRE participants were included (mean [SD] age, 40.40 [14.58] years). Most were female (3013 of 4448 [67.7%]) and aged 18 to 49 years (3338 of 4541 [73.5%]). Applying 5 published definitions for long COVID yielded a prevalence that ranged from 30.84% (95% CI, 29.33%-32.40%) to 42.01% (95% CI, 40.37%-43.66%) at 3 months and 14.23% (95% CI, 13.01%-15.55%) to 21.94% (95% CI, 20.47%-23.47%) at 6 months postinfection; in the 5 comparator studies, reported prevalence of long COVID at 1 to 5 months postinfection ranged from 2.6% (&#x2265;84 days) to 47.4% (3-5 months) and at 6 or more months postinfection ranged from 10.0% (95% CI, 8.8%-11.0%) to 61.9% (6-11 months). Using participants' self-reported long COVID as a criterion standard, existing published definitions had low-to-moderate sensitivity (up to 66.32% [95% CI, 62.59%-69.90%] at 3 months and 45.53% [95% CI, 41.51%-49.60%] at 6 months) and high specificity (up to 81.29% [95% CI, 79.32%-83.15%] at 3 months and 94.26% [95% CI, 92.98%-95.37%]) at 6 months.<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, variability in long COVID prevalence across published definitions highlights the need for a standardized, validated definition to improve clinical recognition and research comparability, ultimately guiding more accurate diagnosis and treatment strategies.},
}
@article {pmid40793886,
year = {2025},
author = {Durlach, M and Manchado Bruno, A and Rotondaro, JC and Khoury, M and Suarez, JP},
title = {[Persistent symptoms in healthcare workers recovered from COVID-19].},
journal = {Medicina},
volume = {85},
number = {4},
pages = {734-742},
pmid = {40793886},
issn = {1669-9106},
mesh = {Humans ; *COVID-19/complications/diagnosis/physiopathology/epidemiology ; Male ; Female ; *Health Personnel/statistics &amp; numerical data ; Adult ; Middle Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: There is no consensus on the definition of post-acute COVID-19 syndrome. Current definitions do not consider the number, severity or prior chronic symptoms. Our aims were to describe the frequency of "new" persistent symptoms (without taking into account those already present before pandemic) following acute COVID-19 and compare with those who did not present the disease.<br><br>MATERIALS AND METHODS: We collected Information on 19 symptoms at two points: pre-pandemic and at survey time, through a self-administered survey targeted at health workers working in person during the pandemic.<br><br>EXCLUSION CRITERIA: acute COVID-19 (or within 21 days of the initial symptom). All COVID-19 participants had previous PCR-confirmed diagnosis.<br><br>RESULTS: Among 249 participants, 73 (29.3%) had had a diagnosis of COVID-19 and 176 (70.7%) had not. 43.8% reported at least one pre-pandemic symptom, with no significant differences between groups (44.3% vs. 42.5%, p=0.789). The median interval between COVID-19 acute illness and survey was 137 (range 38-164). The COVID-19 group reported higher frequency of "new" symptoms (39.7% vs. 12.5%, p=0.000, RR 3.17; 95% CI 1.96-5.14) with a risk difference of 27.2% (95% CI 14.98-39.46). 89% of the COVID-19 group with persistent symptoms had = 2 symptoms, and 69%, had = 3.<br><br>DISCUSSION: The 39.7% of the COVID-19 group had persistent "new" symptoms, 27% more than the nonCOVID group. It is important to unify current definitions of post-COVID syndrome and consider including other aspects such as number, severity prior chronic symptoms.},
}
@article {pmid40792393,
year = {2025},
author = {Macnaughtan, J and Chau, KY and Brennan, E and Toffoli, M and Spinazzola, A and Hillman, T and Heightman, M and Schapira, AHV},
title = {Mitochondrial function is impaired in long COVID patients.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2528167},
pmid = {40792393},
issn = {1365-2060},
mesh = {Humans ; Middle Aged ; Male ; Female ; *COVID-19/complications/physiopathology/metabolism ; *Mitochondria/metabolism ; Aged ; Adult ; Prospective Studies ; Case-Control Studies ; Leukocytes, Mononuclear/metabolism ; SARS-CoV-2 ; Oxygen Consumption ; Quality of Life ; },
abstract = {BACKGROUND: The Long COVID syndrome is a major global health problem, affecting approximately 10-20% of individuals infected with SARS-CoV-2 virus with many remaining symptomatic beyond one year. Fatigue, reduced exercise tolerance and hyperlactataemia on minimal exertion have led to the suggestion of a bioenergetic defect. We hypothesised that mitochondrial dysfunction is a pathological feature in Long COVID cases and would correlate with clinical outcome.<br><br>METHODS: This prospective, case-controlled, observational study recruited 27 participants with an established diagnosis of Long COVID syndrome from a single tertiary clinic together with 16 age-matched controls aged 25-65&#x2009;years. Seahorse-based mitochondrial flux analysis and bioenergetics profile of isolated peripheral blood mononuclear cells (PBMCs) was performed and correlated with clinical phenotype.<br><br>FINDINGS: Long COVID cases had an increased baseline and ATP-induced oxygen consumption rate with a significant attenuation in tetramethylrhodamine methyl ester perchlorate fluorescence response to oligomycin. Correlations were observed between mitochondrial function and autonomic health, quality of life and time from index infection. Sex-specific&#xa0;differences were also observed.<br><br>INTERPRETATION: PBMCs from Long COVID subjects exhibit an exceptional and distinctive change in ATP synthase, as it contributes to the mitochondrial membrane potential rather than using it exclusively to generate ATP. The findings suggest that the enzyme runs both forward and reverse reactions, synthesising and hydrolysing ATP. The correlation of mitochondrial function with clinical phenotype in Long COVID may indicate a causal relationship and warrants further validation in larger scale studies.},
}
@article {pmid40791613,
year = {2025},
author = {Sujarwoto, S and Holipah, H and Andarini, S and Aknuranda, I and Sahputri, RAM and Sarwono, A and Kusharyanto, PG and Kusumo, BE and Maharani, A},
title = {Association between vaccination uptake, vaccine type, and long COVID in rural Indonesia.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1598246},
pmid = {40791613},
issn = {2296-2565},
mesh = {Humans ; Indonesia/epidemiology ; *COVID-19/prevention &amp; control/epidemiology ; Female ; Male ; Adult ; Cross-Sectional Studies ; *COVID-19 Vaccines/administration &amp; dosage ; Middle Aged ; *Rural Population/statistics &amp; numerical data ; *Vaccination/statistics &amp; numerical data ; SARS-CoV-2 ; Adolescent ; Young Adult ; },
abstract = {INTRODUCTION: Long COVID affects a significant proportion of individuals after SARS-CoV-2 infection. While vaccines reduce severe disease, their effect on long COVID remains unclear, especially in rural, resource-limited settings. This study investigates the association between vaccination status, vaccine type, and long COVID in Malang Regency, East Java.<br><br>METHODS: We analysed cross-sectional data from 5,735 adults who tested positive for COVID-19 between June 2022 and June 2023. Long COVID was defined as persistent symptoms &#x2265;12&#x202f;weeks post-infection. Data on vaccination status, vaccine type, comorbidities, and sociodemographic characteristics were collected through surveys and linked to immunisation records. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for long COVID, including stratified analyses by vaccine platform and dose.<br><br>RESULTS: Long COVID was reported by 56.2% of participants. Compared to unvaccinated individuals, those who received mRNA vaccines had significantly lower odds of long COVID, Moderna (OR&#x202f;=&#x202f;0.341, 95% CI: 0.067-0.887) and Pfizer (OR&#x202f;=&#x202f;0.220, 95% CI: 0.057-0.771), while recipients of non-mRNA vaccines, such as Sinovac (OR&#x202f;=&#x202f;1.205, 95% CI: 1.038-1.331), had increased odds. A dose-response relationship was observed for mRNA vaccines, with two doses (OR&#x202f;=&#x202f;0.420, 95% CI: 0.402-0.511) and three or more doses (OR&#x202f;=&#x202f;0.743, 95% CI: 0.601-0.712) both reducing risk compared to no mRNA vaccination. Older age, hypertension, higher education, and higher income were also associated with increased long COVID risk.<br><br>CONCLUSION: mRNA COVID-19 vaccines and full vaccination schedules are strongly protective against long COVID in rural Indonesia. These findings highlight the need to improve access to mRNA vaccines and booster doses to reduce long-term COVID-19 impacts in underserved populations.},
}
@article {pmid40791479,
year = {2025},
author = {Morad, H and Vanhala, T and Kisiel, MA and Andreason, A and Li, M and Andersson, G and Laurell, G and Finger, TE and Hellekant, G},
title = {Taste dysfunction in Long COVID.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40791479},
issn = {2692-8205},
support = {R01 DC014728/DC/NIDCD NIH HHS/United States ; },
abstract = {Persistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (Long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subjects diagnosed with COVID-19 and who experienced taste disturbances more than 12 months after testing positive for SARS-CoV-2. To objectively establish the nature of taste deficit, we used the WETT taste test, which quantifies the subject's ability to taste each of the five taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied five to eight fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud structure and innervation, and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only three showed overall taste scores below the 10[th] percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLCβ2-dependent taste qualities (sweet, umami, bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved taste bud structure and innervation, but with occasional disorganized taste buds and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely -- more frequently involving PLCβ2-dependent taste qualities -- but is not due to wholesale disruption of the taste periphery.},
}
@article {pmid40791384,
year = {2025},
author = {Dang, H and Edwards, CE and Kato, T and Reidel, B and Meganck, RM and Esther, CR and Ehre, C and Fulcher, ML and Bailey, AB and Cooley, MR and Mikami, Y and Asakura, T and Hawkins, PE and Furusho, M and Myers, JL and Konopka, K and Gerayeli, FV and Park, HY and Sin, DD and Livraghi-Butrico, A and Okuda, K and Pickles, RJ and Klein, S and Randell, SH and O'Neal, WK and Baric, RS and Boucher, RC},
title = {Airway epithelial SARS-CoV-2 infectious and repair responses: relationships to age, sex, and post-COVID pulmonary syndromes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40791384},
issn = {2692-8205},
support = {P30 DK065988/DK/NIDDK NIH HHS/United States ; R01 AI089728/AI/NIAID NIH HHS/United States ; U19 AI116484/AI/NIAID NIH HHS/United States ; },
abstract = {The long-term pulmonary sequelae of SARS-CoV-2 respiratory infections reflect infection severity, innate and adaptive immunity, and respiratory epithelial repair. This study investigated the acute and reparative responses as a function of age and sex in primary human bronchial epithelial (HBE) cultures utilizing a 14-day SARS-CoV-2 infection protocol. SARS-CoV-2 infection peaked at 3 days post-infection (dpi) with an ~ 2 log titer suppression at 14 dpi. SARS-CoV-2 infection induced interferon, interferon-induced gene, and cell damage responses. No age- or sex-dependent effects on SARS-CoV-2 infection were detected. Airway epithelia repaired to an abnormal mucus metaplastic/inflammatory state that reflected potentially beneficial and adverse consequences at 14 dpi. Repair processes were infection severity-dependent, not sex-dependent, and were more robust in young donor cultures. Analyses of long-COVID subjects with persistent pulmonary fibrosis or persistent bronchitic airway diseases exhibited expression of HBE 14 dpi failed repair gene signatures, including ISG gene signatures. Human airway epithelial repair post-SARS-CoV-2 is prolonged and incomplete in vitro over 14 days, and persistently abnormal repair may contribute to phenotypes of people with long-COVID pulmonary syndrome.},
}
@article {pmid40790065,
year = {2025},
author = {Borhani, S and Silva, I and Damiano, RJ and Feng, T and Wang, C and Liu, L and Salvati, E and Mariani, S and Conroy, B},
title = {Automatic detection of persistent physiological changes after COVID infection via wearable devices with potential for long COVID management.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {29443},
pmid = {40790065},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/physiopathology/diagnosis/therapy ; *Wearable Electronic Devices ; Retrospective Studies ; Male ; Heart Rate ; Female ; SARS-CoV-2 ; Adult ; Military Personnel ; Middle Aged ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to post-acute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, a chronic multisystemic condition with diverse symptoms and no objective diagnostic test. In this retrospective study, we developed a data-driven method to objectively detect persistent physiological changes using wearable device data in a large cohort of over 12,000 US military personnel. We analyzed physiological data from 663 symptomatic COVID-19 positive cases and 2,513 asymptomatic COVID-19 negative controls. Our method identified persistent physiological changes in 9.4% of COVID-19 positive individuals, most commonly manifesting as elevated nightly heart rate and reductions in some heart rate variability metrics. Our findings demonstrate that wearable technology can be used to objectively detect chronic physiological changes beyond the acute phase of COVID-19 illness. Although our method requires further clinical validation, it could potentially provide objective metrics to help standardize Long COVID diagnosis criteria.},
}
@article {pmid40789995,
year = {2025},
author = {Bao, W and Chen, S and Hong, N and Ye, G and Li, C and Xie, J and Li, P and Li, H and Wang, Y and Liu, J and Niu, X and Zhang, Y},
title = {Longitudinal relationships between changes in post-COVID mental fatigue and neuropsychiatric symptoms across distinct recovery trajectories.},
journal = {Inflammopharmacology},
volume = {33},
number = {9},
pages = {5471-5481},
pmid = {40789995},
issn = {1568-5608},
support = {82202121//the national natural science foundation of China/ ; },
mesh = {Humans ; Male ; *COVID-19/psychology/complications ; Female ; Middle Aged ; Longitudinal Studies ; Adult ; *Mental Fatigue/psychology/etiology/epidemiology ; Fatigue/psychology/etiology ; Depression/psychology ; Anxiety/psychology ; Cognitive Dysfunction/psychology ; Stress Disorders, Post-Traumatic/psychology ; Sleep Wake Disorders/psychology ; Aged ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Persistent fatigue, often accompanied by neuropsychiatric symptoms (e.g., cognitive impairment, sleep disorders, depression, anxiety, and PTSD), commonly referred to as "long COVID". Fatigue is multidimensional, comprising physical, psychological, and situational components. However, the relationships between these fatigue dimensions and co-occurring neuropsychiatric symptoms remain unclear. This study aimed to (1) examine the time-varying characteristics of post-COVID fatigue and (2) determine whether specific fatigue dimensions uniquely affect neuropsychiatric symptoms in long COVID.<br><br>METHODS: We analyzed neuropsychiatric assessments from 233 individuals at 1 and 3&#xa0;months post-infection using Canonical Correlation Analysis (CCA). Participants were categorized into four groups based on fatigue recovery trajectories: persistent fatigue, alleviated fatigue, new-onset fatigue, and no fatigue. Longitudinal CCA assessed relationships between changes in fatigue dimensions and cognitive impairments (memory, executive function) and psychiatric symptoms (anxiety, depression, PTSD, and sleep disturbances) from the acute to chronic phase.<br><br>RESULTS: Physical fatigue was dominant in the acute phase, while mental fatigue became more prominent at 3&#xa0;months. Across both phases, all fatigue dimensions were strongly associated with depression, anxiety, PTSD, and sleep disturbances, with mental fatigue showing the strongest impact (canonical loadings: &#x3c1;&#x2009;=&#x2009;-&#xa0;0.875 at 1&#xa0;month; &#x3c1;&#x2009;=&#x2009;-&#xa0;0.914 at 3&#xa0;months). In the persistent fatigue group, mental fatigue was closely linked to anxiety, depression, and cognitive impairments, including recognition and short-term recall (&#x3c1;&#x2009;=&#x2009;-&#xa0;0.677). No significant longitudinal associations were observed in the alleviated, new-onset, or no-fatigue groups.<br><br>CONCLUSIONS: Mental fatigue plays a central role in the chronic phase of recovery, significantly impacting cognitive and psychiatric health in individuals with persistent fatigue. Targeted interventions addressing mental fatigue are essential for improving long COVID outcomes.},
}
@article {pmid40789627,
year = {2025},
author = {Liu-Galvin, R and Orlando, FA and Khan, T and Wozniak, GD and Mainous, AG},
title = {Long COVID and Days of Work Missed Due to Illness or Injury by Adults in the United States, 2022.},
journal = {Journal of the American Board of Family Medicine : JABFM},
volume = {38},
number = {3},
pages = {551-555},
pmid = {40789627},
issn = {1558-7118},
mesh = {Humans ; *COVID-19/epidemiology/complications/economics ; United States/epidemiology ; Adult ; Male ; Female ; Middle Aged ; *Sick Leave/statistics &amp; numerical data ; Young Adult ; Adolescent ; SARS-CoV-2 ; *Absenteeism ; *Wounds and Injuries/epidemiology ; },
abstract = {INTRODUCTION: There are concerns of postacute sequelae of COVID-19, but the impact of long COVID on the US workforce is unclear.<br><br>METHODS: We analyzed the nationally representative 2022 Medical Expenditure Panel Survey (MEPS). Adult (aged 18 or above) full time workers were classified as those who had never had COVID-19, those who had COVID-19 without long COVID, and those who had long COVID. The number of days of work missed due to illness in 2022 was assessed in unadjusted negative binomial regressions and those adjusted for paid sick leave, age, sex, race and comorbidities.<br><br>RESULTS: Among 125,151,402 (weighted) adults, 42.9% never had COVID-19, 49.6% had COVID-19 without long COVID, and 7.5% had long COVID. Patients with long COVID missed more than 8&#x2009;days of work in a year which was 171% higher than patients without COVID-19% and 62% higher than those who had COVID-19 without long COVID. After adjusting for potential confounding variables, patients who had COVID-19 without long COVID had a greater rate of missing work (IRR 1.75; 95% CI 1.51, 2.04) compared with those who did not have COVID-19. Long COVID patients had an even higher rate of missing work (IRR 2.21; 95% CI 1.79, 2.73) compared with those who did not have COVID-19.<br><br>DISCUSSION: An additional outcome for patients with long COVID is an impact on the workforce and significantly more missed workdays.},
}
@article {pmid40786650,
year = {2025},
author = {Zhu, Y and Qin, X and Lu, Y and Yu, Y and Liu, R and Zhu, R and Su, KP and Wang, F},
title = {The impact of acute COVID-19 symptoms on insomnia: A longitudinal study among medical students.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {48},
number = {},
pages = {101067},
pmid = {40786650},
issn = {2666-3546},
abstract = {OBJECTIVE: The COVID-19 pandemic has profoundly disrupted global mental health. Medical students, already vulnerable to high stress, experience heightened psychological distress. This study aimed to investigate the association between acute COVID-19 infection and the development of psychological symptoms in medical students, exploring the role of specific COVID-19 symptoms and lifestyle factors.<br><br>METHODS: A longitudinal study of 2359 medical students assessed psychological symptoms (depression, anxiety, insomnia) before and after COVID-19 infection. Logistic regression models, adjusted for confounders, examined the relationship between COVID-19 status (with or without infection), and the onset of psychological symptoms. The study also explored acute COVID-19 symptoms and lifestyle factors associated with psychological symptoms in the COVID-19 infected (COVID+) group.<br><br>FINDINGS: The COVID&#xa0;+&#xa0;group exhibited significantly greater increases in depression and insomnia compared to non-infected group. COVID-19 infection was significantly associated with the onset of insomnia post-infection (OR [95&#xa0;% CI] 1.83 [1.05-3.21]). Moderate to severe acute symptoms, including sleep disturbances (2.20 [1.17-4.14]), decreased attention/memory (2.47 [1.02-6.00]), and breathlessness (2.05 [1.08-3.85]), were identified as risk factors for onset of insomnia. Regular exercise was found to be negatively associated with the onset of insomnia (0.54 [0.33-0.88]).<br><br>CONCLUSION: Early intervention targeting these acute-phase risk symptoms is crucial for preventing long-term insomnia. Regular exercise is effective in preventing the development of insomnia in medical students following COVID-19 infection. These findings will assist in formulating targeted interventions to address recurrent infections in the post-pandemic era.},
}
@article {pmid40783949,
year = {2025},
author = {O'Hara, ME and McDuff, K and Wei, H and McCorkell, L and Thomson, C and Kelly, M and Goulding, S and O'Donovan, I and O'Connell, S and Stokes, R and Malli, N and St Clair-Sullivan, N and Chan Carusone, S and Cheung, AM and Erlandson, KM and Bannan, C and Townsend, L and Bergin, C and Vera, JH and Harding, R and Avery, L and Brown, DA and O'Brien, KK},
title = {Community Engagement in Long Covid Research: Process, Evaluation and Recommendations From the Long COVID and Episodic Disability Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70365},
pmid = {40783949},
issn = {1369-7625},
support = {//This study was funded by the Ontario Strategy for Patient-Oriented Research (SPOR) SUPPORT Unit, which is supported by the Canadian Institutes of Health Research (CIHR), the Province of Ontario, and partner Ontario hospital foundations and institutes. The Long COVID and Episodic Disability Study was funded by the CIHR, Emerging COVID-19 Research Gaps and Priorities Funding Opportunity (Funding Research Number: GA4-177753). K.K.O. was supported by a Canada Research Chair in Episodic Disability and Rehabilitation from the Canada Research Chairs Program (CRC-2022-00510)./ ; },
mesh = {Humans ; *COVID-19/epidemiology ; *Community Participation/methods ; *Community-Based Participatory Research/organization &amp; administration ; *Persons with Disabilities ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long Covid and other infection-associated chronic condition communities have been integral in advocating for patient engagement in all stages of research, from design and conduct, and implementation, through to interpretation and knowledge translation; nevertheless, the process varies across research teams. In this paper, we (1) describe our process undertaking a community-engaged Long Covid research study; (2) evaluate our community-engaged approach, highlighting strengths and limitations with our process; and (3) identify recommendations for engaging in community-engaged patient-oriented research in Long Covid.<br><br>METHODS: Guided by the 4PI (Principles; Purpose; Presence; Process; Impact) Framework and Patient-Led Research Scorecards, we describe our community-engaged approach within the Long COVID and Episodic Disability Study, followed by an evaluation of our community engagement using a multistage consultation with members of the Long COVID and Episodic Disability Study team. We conducted an online group-based discussion among persons with lived experiences and administered a web-based Scorecard questionnaire rating the collaboration as it relates to four domains of patient burden, governance, integration into the research process, and organisation readiness to all members of the team, to assess strengths and limitations of our approach. Scores ranged from -2 (non-collaboration) to +2 (ideal collaboration).<br><br>RESULTS: Ten team members, five of whom were persons with lived experiences, completed the Scorecard questionnaire. Median Scorecard scores ranged from +1 to +2 for all domains. Five team members with lived experiences, representing four community support groups and organisations that participated in the community-engagement discussion. We describe the practices and principles that enabled meaningful community engagement, with the strengths and limitations of our approach embedded throughout.<br><br>CONCLUSION: Our community-engaged approach to the Long COVID and Episodic Disability Study enhanced the quality and relevance of the study to the community while highlighting areas to heighten meaningful engagement throughout. This study builds on foundational community-based research principles of patient-oriented research. Recommendations derived from our experiences may be used by other research teams conducting community-engaged patient-oriented research.<br><br>The Long COVID and Episodic Disability Study is a community-engaged research study involving 25 members, including 12 persons living with long Covid, 13 researchers and 5 clinicians (categories are not mutually exclusive), referred to as the Full Team. Persons with lived experiences possessed a range of professional and personal experiences spanning research, clinical, policy and private sector/business contexts; team members wore multiple hats and perspectives which collectively strengthened the diversity of expertise, perspectives and insights to the team and process. Engagement of people with lived experiences with Long Covid ensured that the study was fully co-created with people living with Long Covid. During the development of the study proposal, community partners from organisations in Canada, Ireland, the United Kingdom and the United States, who were linked to larger networks of people living with Long Covid, were purposefully invited to join the study team. Several Long Covid community networks and organisations, represented by persons living with Long Covid, were involved in all stages of the research, including: COVID Long-Haulers Support Group Canada (S.G.); Long COVID Advocacy Ireland (I.O., S.O. and R.S.); Long COVID Ireland (N.R. and R.S.); Long COVID Physio (D.A.B. and C.T.); Long Covid Support UK (M.O.H.); and Patient-Led Research Collaborative (L.M., N.M. and H.W.). These representatives along with the Co-PIs (K.K.O. and D.A.B.) and co-ordinator (K.M.) comprised the Core Long COVID and Episodic Disability Community Collaborator Team (Core Team). Team members with lived experiences were provided yearly remuneration for their time and expertise dedicated to the study, either as an individual, or to the community organisation which they represented on the study according to their preference.},
}
@article {pmid40783164,
year = {2025},
author = {Carazo, S and Ouakki, M and Nicolakakis, N and Falcone, EL and Skowronski, DM and Durand, MJ and Coutu, MF and Décary, S and Dialahy, IZ and Drescher, O and Canitrot, E and McGinn, CA and Latouche, P and Laforce, R and Dallaire, C and Denis, G and Piché, A and De Serres, G},
title = {Long COVID risk and severity after COVID-19 infections and reinfections: A retrospective cohort study among healthcare workers.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {159},
number = {},
pages = {108012},
doi = {10.1016/j.ijid.2025.108012},
pmid = {40783164},
issn = {1878-3511},
mesh = {Humans ; *COVID-19/epidemiology/virology ; Retrospective Studies ; Female ; Male ; *Health Personnel/statistics &amp; numerical data ; Adult ; Middle Aged ; SARS-CoV-2 ; Severity of Illness Index ; Prevalence ; *Reinfection/epidemiology ; Quebec/epidemiology ; Incidence ; Risk Factors ; },
abstract = {OBJECTIVE: We evaluated long COVID risk, prevalence and severity in a population-based cohort of Quebec healthcare workers (HCWs), in Canada, and the effect of reinfections, variants, and acute infection's severity.<br><br>METHODS: Retrospective survey-based cohort study conducted in Spring 2023. HCWs self-reporting COVID-19-attributed symptoms lasting &#x2265;12 weeks were long COVID cases, classified as mild, moderate, or severe based on self-perceived symptom intensity and compared to controls. We estimated long COVID prevalence and cumulative incidence by number of infections, and following first and subsequent infections stratified by infecting variant and acute COVID-19 severity. Adjusted risk ratios were computed using robust Poisson models.<br><br>RESULTS: 22 496 (of 397,222 invited HCWs) and 3 978 (of 10,500) participated in the electronic and telephone surveys. Long COVID cumulative risk among infected participants was 17.0% (95% CI:16.3-17.6%), increasing with number of infections. Estimated prevalence was 5.6% (95% CI:4.9-6.3%). Reinfections (vs first infection), Omicron (vs ancestral variant) and nonsevere acute infection (vs severe) were associated, respectively, with 40%, 34% and 72% lower long COVID risk. Severe cases exhibited multiple symptoms and substantial functional limitations.<br><br>CONCLUSION: Long COVID is a common and disabling condition. With the ongoing SARS-CoV-2 transmission, interventions targeting the frequency and severity of reinfections may reduce future long COVID burden.},
}
@article {pmid40783127,
year = {2025},
author = {McInnes, K and Fanucchi, S},
title = {A clot to uncover: SARS-CoV-2 nucleocapsid can outcompete the FOXP3 forkhead domain for DNA binding in vitro.},
journal = {Biochimie},
volume = {238},
number = {Pt B},
pages = {172-180},
doi = {10.1016/j.biochi.2025.08.006},
pmid = {40783127},
issn = {1638-6183},
mesh = {*Forkhead Transcription Factors/metabolism/chemistry/genetics ; Humans ; *SARS-CoV-2/metabolism ; *COVID-19/metabolism/virology ; *DNA/metabolism ; Protein Binding ; *Coronavirus Nucleocapsid Proteins/metabolism/chemistry ; Protein Domains ; },
abstract = {During COVID-19, systemic coagulopathy can lead to strokes and embolisms and may also contribute to long COVID. This coagulopathy is the result of overactivated platelets in circulation that lead to inappropriate clot formation. FOXP3 is a transcription factor involved in platelet development. Loss of FOXP3 function leads to abnormal platelets resembling those seen during COVID-19. Thus, FOXP3 may be dysregulated in COVID-19. The SARS-CoV-2 nucleocapsid (NC) is a multifunctional protein typically associated with viral genome packaging and virion assembly. However, it is also capable of binding DNA and may alter host gene expression. Here, potential interactions between the DNA-binding forkhead domain (FHD) of FOXP3 and the SARS-CoV-2 NC were investigated. Identification of a novel interaction between FOXP3 and SARS-CoV-2 NC may provide new clues to the pathophysiology of COVID-19. To address this aim, both proteins were overexpressed in T7 E. coli, purified via immobilised metal affinity chromatography, and monitored for interactions in the absence and presence of DNA using pull-down assays, electrophoretic mobility shift assays, and fluorescence anisotropy. A direct interaction was identified between the two proteins in the absence of DNA in vitro. Additionally, both proteins were found to bind DNA simultaneously under limiting conditions, but competed for binding under saturating conditions, where excess NC led to dissociation of FHD from the FHD-NC-DNA complex. This result implicates NC in FOXP3 dysfunction, potentially contributing to the coagulopathy and other symptoms observed during COVID-19. This work may inform future therapeutic strategies for severe COVID-19.},
}
@article {pmid40782303,
year = {2026},
author = {Shi, S and YongWang, },
title = {Letter to: identifying influencing factors and constructing a prediction model for long COVID-19 in hemodialysis patients.},
journal = {International urology and nephrology},
volume = {58},
number = {2},
pages = {721-722},
pmid = {40782303},
issn = {1573-2584},
}
@article {pmid40782207,
year = {2025},
author = {Roge-Gurecka, I and Kivite-Urtane, A and Pavare, J},
title = {Two-year follow-up on multisystem inflammatory syndrome in children (MIS-c): findings from a tertiary paediatric hospital in Latvia.},
journal = {European journal of pediatrics},
volume = {184},
number = {9},
pages = {542},
pmid = {40782207},
issn = {1432-1076},
mesh = {Humans ; Child ; Male ; Female ; Adolescent ; *Systemic Inflammatory Response Syndrome/physiopathology/diagnosis/therapy/complications ; Follow-Up Studies ; Child, Preschool ; Prospective Studies ; *COVID-19/complications/therapy/diagnosis ; Longitudinal Studies ; Infant ; Tertiary Care Centers ; Latvia ; Hospitals, Pediatric ; Fatigue/etiology ; },
abstract = {UNLABELLED: This study aimed to assess long-term recovery from multisystem inflammatory syndrome in children (MIS-c) 24 months after admission. This prospective longitudinal cohort study included 21 children diagnosed with MIS-c according to Centers for Disease Control and Prevention (CDC) criteria and admitted to Children's Clinical University Hospital in Riga. Outpatient follow-up consisted of repeated visits at 3, 6, 12, and 24 months after the acute phase of MIS-c. In addition to the initial interview and physical examination, the patients were asked to perform functional tests (six-minute walking test (6-MWT) and orthostatic intolerance test (OIT)) and complete validated tools (Chalder Fatigue Questionnaire (CFQ-11) and Karolinska Sleep Questionnaire (KSQ)). The median age of the study group was 6 years (IQR, 5.0-10.0 years; range, 1-16 years). The KSQ showed that sleep quality, non-restorative sleep, and daytime sleepiness were more associated with the 1-3-month period than with long-term sequelae. At 1-3 months, all children exhibited physical and psychological fatigue (bi-modal score ≥ 4). By 6 months, no patient showed fatigue (bi-modal score < 3). The OIT showed no signs of orthostatic intolerance, orthostatic hypotension, or POTS among patients. Heart rate and blood pressure changes were mild. The 6-MWT showed significant improvement in walking distance.<br><br>CONCLUSIONS: &#xa0;Most improvements in sleep quality, reduction in fatigue, orthostatic compensation, and aerobic capacity occur within the first 6&#xa0;months after acute MIS-c, with no long-term sequelae.<br><br>WHAT IS KNOWN: &#x2022; Multisystem inflammatory syndrome in children (MIS-c) is a potentially life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. &#x2022; Data on long-term outcomes of patients with MIS-c are scarce, providing very limited insights into children's well-being after 12 months.<br><br>WHAT IS NEW: &#x2022;&#xa0;Our two-year study indicated that for most patients, physical and psychological health improvements occurred within the first 6 months after acute MIS-c, without long-term consequences. &#x2022; RDW/PLT may serve as a practical early marker of oxidative stress response in neonates, reinforcing the safety of phototherapy while raising questions for preterm care.},
}
@article {pmid40780102,
year = {2025},
author = {Leitner, M and Pinter, D and Ropele, S and Koini, M},
title = {Functional connectivity changes in long-Covid patients with and without cognitive impairment.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {191},
number = {},
pages = {74-89},
doi = {10.1016/j.cortex.2025.07.005},
pmid = {40780102},
issn = {1973-8102},
mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/physiopathology/diagnostic imaging/etiology ; Magnetic Resonance Imaging/methods ; *COVID-19/physiopathology/complications/diagnostic imaging/psychology ; Middle Aged ; Aged ; *Brain/physiopathology/diagnostic imaging ; *Nerve Net/physiopathology/diagnostic imaging ; Neuropsychological Tests ; Neural Pathways/physiopathology/diagnostic imaging ; Executive Function/physiology ; Adult ; SARS-CoV-2 ; Gray Matter/diagnostic imaging ; Connectome ; },
abstract = {Long-Covid is associated with cognitive deficits in memory, attention, or executive function. However, the associated cerebral structural and functional changes are insufficiently studied to date. We investigated 39 long-Covid patients with (n = 16) and without (n = 23) cognitive impairment. Impairment was defined by a pronounced deficit (-1.5 SD) in at least one cognitive domain including memory, attention, executive function, and verbal fluency. All participants underwent structural and functional resting-state magnetic resonance imaging (MRI). We assessed differences in resting-state networks (within and between networks) between both groups as well as structural differences in total gray matter and subcortical volumes. Both groups did not differ in demographic or disease-related characteristics. Patients with cognitive deficits showed higher functional connectivity (FC) between the default mode network (DMN) and parts of the posterior supramarginal gyrus, angular gyrus and posterior-occipital part of the middle temporal gyrus, compared to those cognitively unimpaired. In addition, inter-network analyses indicated a stronger connectivity between the visual and ventral stream network in those with cognitive impairment. We found no volumetric differences between the two groups. Our results indicate that altered FC with the DMN as well as a stronger connectivity between the visual and ventral stream network in cognitively impaired long-Covid patients are associated with worse cognitive performance and therefore suggests a maladaptive functional change.},
}
@article {pmid40779512,
year = {2025},
author = {Martínez-Borba, V and Peris-Baquero, &#xd3; and Prieto-Rollán, I and Osma, J and Del Corral-Beamonte, E},
title = {Preliminary feasibility and clinical utility of the Unified Protocol for the transdiagnostic treatment of emotional disorders in people with long COVID-19 condition: A single case pilot study.},
journal = {PloS one},
volume = {20},
number = {8},
pages = {e0329595},
pmid = {40779512},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/psychology/complications ; Pilot Projects ; Male ; Female ; Middle Aged ; Feasibility Studies ; Adult ; SARS-CoV-2/isolation &amp; purification ; Patient Satisfaction ; Depression/therapy ; },
abstract = {PURPOSE: The implementation of psychological interventions in long COVID-19 patients is still very limited. This study aims to analyze the feasibility and preliminary utility of the Unified Protocol (UP), for the psychological treatment of emotional disorders in long COVID-19 patients.<br><br>METHODS: 12 long COVID-19 patients (mean age&#x2009;=&#x2009;47.92; SD&#x2009;=&#x2009;13.18) presenting emotional disorders/symptoms received the UP through 8 online sessions.<br><br>RESULTS: All participants completed the UP psychological program, attending all eight sessions and the 6-month follow-up appointment. However, adherence to the assessment protocol was lower, with a 33% dropout rate at the 6-month follow-up. High satisfaction was reported with both the UP program (mean&#x2009;=&#x2009;9.75) and the online format. Satisfaction with individual UP modules ranged from 7.17 to 9 points (from 0&#x2009;=&#x2009;any satisfaction to 10&#x2009;=&#x2009;highest satisfaction). Qualitative feedback emphasized the usefulness of the UP program, with some participants suggesting additional contents (i.e., training in assertive communication skills), more personalized modules (i.e., providing just some UP modules) or increasing the number of sessions. In terms of the UP clinical utility, 25 mental clinical diagnoses were established at pre-assessment; 50% of participants no longer met criteria for a mental clinical diagnosis at post-assessment, increasing to 67% at follow-up. Most therapeutic objectives were achieved or initiated over the course of the intervention (78% at post-assessment; 86% at follow-up). At post-assessment significant improvements were observed in anxiety (8 participants), depression (9 participants), emotion dysregulation (4 participants) and quality of life scores (7 participants), although 2 participants did not maintain these gains in emotion regulation and quality of life at follow-up.<br><br>CONCLUSION: The promising results of the UP in terms of high participant satisfaction and clinical improvements in anxiety and depression scores suggest that the UP could be a valuable psychological intervention for individuals with long COVID-19 and comorbid emotional disorders. The modest improvements found in other outcomes highlighted the need to better adapt the psychological interventions for long COVID-19 patients.},
}
@article {pmid40778940,
year = {2026},
author = {Anujuo, KO and Ikuabe, PO and Ebuenyi, ID},
title = {Exploring Correlates of Mental Health and Employment in Individuals With Long COVID: A Secondary Data Analysis.},
journal = {Journal of occupational and environmental medicine},
volume = {68},
number = {1},
pages = {74-79},
doi = {10.1097/JOM.0000000000003522},
pmid = {40778940},
issn = {1536-5948},
mesh = {Humans ; *COVID-19/psychology/epidemiology ; Male ; Cross-Sectional Studies ; Female ; *Employment/statistics &amp; numerical data/psychology ; Middle Aged ; Adult ; *Mental Health ; *Mental Disorders/epidemiology ; SARS-CoV-2 ; Socioeconomic Factors ; Aged ; Secondary Data Analysis ; },
abstract = {OBJECTIVE: Long COVID is a major public health challenge with mental health and socioeconomic consequences for affected individuals. We examined the mental health and socioeconomic correlates of long COVID using a secondary dataset.<br><br>METHODS: A cross-sectional study was conducted with 1901 participants. Outcome variable was employment and with long COVID as a major predictor. The association between long COVID and employment was assessed using logistic regression analysis.<br><br>RESULT: 60.9% of participants with long COVID reported being employed compared to 61.7% of participants without long COVID. 53.2% of participants with mental health reported being employed compared to 44.7% of participants without mental health.<br><br>CONCLUSIONS: This study highlights existing challenges in employment among individuals with long COVID and mental disorders. There is a need to develop interventions that address both the mental health and socioeconomic needs of individuals with long COVID.},
}
@article {pmid40778199,
year = {2025},
author = {Chow, JSF and Maurya, N and San Miguel, S and Teramayi, R and Parameswaran, A and D'Souza, A and Melbourne, G and Descallar, J and Juhn, Y and Chan, E and Pong, J},
title = {Remote, smart telemonitoring of COVID-19 survivors for early detection of deterioration in cardiac health (the PARTMO study).},
journal = {Frontiers in medical technology},
volume = {7},
number = {},
pages = {1534097},
pmid = {40778199},
issn = {2673-3129},
abstract = {INTRODUCTION: This study aims to implement a virtual model of care in the primary healthcare setting, utilising biosensor technologies (S-Patch EX) to remotely monitor and identify clinical signs and symptoms of cardiovascular conditions (mainly arrhythmias) in patients post-COVID-19 infection.<br><br>METHODS: This open-label, non-randomised, observational study was conducted in patients aged 18 years and above, clinically diagnosed with COVID-19 after June 2021, and those residing within Greater Western Sydney. The study involved two arms: the remote monitoring (intervention) and standard care (control) groups. The intervention group comprised patients who were provided with an S-Patch EX to monitor their electrocardiogram. Data were transmitted in real-time to a mobile phone via Bluetooth technology, and results were generated through artificial intelligence (AI) algorithms. All the data were reviewed for arrhythmia detection and escalated to the participant's general practitioner (if detected) to determine the appropriate intervention. The control group was used to compare the rate of cardiac arrhythmia detection against the intervention group. The patient's demographic and longitudinal clinical data were obtained from the electronic medical record system, enabling exploration and comparison of the cohort's characteristics and outcomes. Descriptive analysis was conducted for categorical variables (frequencies and cross-tabulations) and continuous variables (means, standard deviations, and medians). Depending on the nature of data, the groups were compared using t-tests or Chi-square tests. Multivariable Cox regression was used to analyse time to first cardiovascular event post-COVID-19 infection.<br><br>OUTCOME MEASURES: The time to the patient's first cardiovascular event (mainly arrhythmias) post-COVID-19 infection.<br><br>RESULTS: Of 44 patients who provided consent, 40 commenced monitoring. Thirteen patients (32.5%) were detected by the AI algorithms from the S-Patch EX monitoring system to have cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, and ventricular tachycardia. Univariate Cox regression demonstrated that arrhythmia was more likely to be detected in the remote monitoring group (13/40, 32.9%) as compared with the standard care group (7/200, 3.5%) [HR&#x2009;=&#x2009;29.56 (9.95, 87.86), p&#x2009;<&#x2009;0.0001]. Most of the patients were detected with arrhythmia within a 3-month timeframe of monitoring. Twenty-one patients (21/200, 10.5%) from the standard care group visited the emergency department and/or were admitted to the hospital post-COVID-19 infection due to chest pain, shortness of breath/dyspnoea, palpitations, dizziness/light-headedness/presyncope, and nausea. Two patients developed long COVID symptoms (progressive dyspnoea) 2-5 months post-COVID-19 infection.<br><br>CONCLUSIONS: Considering the risk of developing cardiovascular complications post-COVID-19 infection, regular monitoring, reassessment, and evaluation are recommended as a part of post-COVID-19 management for all patients, including young, healthy, and asymptomatic populations. A randomised interventional study with a larger sample size and longer follow-up period is advised for a better understanding of the cardiovascular impact post-COVID infection.},
}
@article {pmid40778129,
year = {2025},
author = {Bruiners, N and Ukey, R and Konvinse, KC and Harris, M and Kalaycioglu, M and Yang, JH and Yang, E and Ganapathi, U and Honnen, W and Andrews, T and Richlin, B and Suarez, C and Gaur, S and Ricciardi, E and Hasan, UN and Cuddy, W and Singh, AR and Bukulmez, H and Kaelber, DC and Kimura, Y and Pinter, A and Napoli, S and Moroso-Fela, S and Kleinman, LC and Horton, DB and Utz, PJ and Gennaro, ML},
title = {Antibody repertoire associated with clinically diverse presentations of pediatric SARS-CoV-2 infection.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40778129},
support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; R33 HD105619/HD/NICHD NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; R38 HL143615/HL/NHLBI NIH HHS/United States ; R33 HD105593/HD/NICHD NIH HHS/United States ; R01 AI158911/AI/NIAID NIH HHS/United States ; R01 AI182319/AI/NIAID NIH HHS/United States ; R01 AI175771/AI/NIAID NIH HHS/United States ; },
abstract = {Pediatric SARS-CoV-2 infection results in clinical presentations ranging from asymptomatic/mild infection to severe pulmonary COVID-19, to Multisystem Inflammatory Syndrome in Children (MIS-C), characterized by hyperinflammation and multi-organ involvement. While various aspects of antibody responses to pediatric SARS-CoV-2 infection manifestations have been reported, parallel studies of antibody responses to viral and self-antigens are understudied. We tested whether clinical presentations of increasing severity corresponded to different antiviral antibody and autoantibody signatures. Using custom arrays, we found that, relative to uninfected subjects, all SARS-CoV-2 infection manifestations were associated with increased autoantibody production, suggesting pediatric SARS-CoV-2 infection as a risk factor for autoimmune complications. Subtle differences were seen in autoantibody patterns among infection groups, with some autoantibodies more associated with mild manifestations and others with severe ones. When we compared MIS-C and severe COVID-19 subjects, we found differences in IgG (mostly IgG1) abundance but not in Fc-mediated effector functions. Thus, MIS-C may be associated with abnormal antibody function, suggesting that this syndrome, and perhaps other post-acute sequelae of SARS-CoV-2 infection, may be associated with antibody dysfunction. Our study shows that the antibody repertoire varies with clinical presentation of SARS-CoV-2 in children and its analysis may help understand long COVID pathogenesis.},
}
@article {pmid40777569,
year = {2025},
author = {Du, H and Du, X and Lei, X and Wang, G and Wang, Z and Du, Y and Bai, F and Yuan, D},
title = {Therapeutic effect of cardiac rehabilitation on patients with long COVID combined with coronary heart disease: a retrospective study.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1560243},
pmid = {40777569},
issn = {2297-055X},
abstract = {OBJECTIVES: To investigate the efficacy of cardiac rehabilitation in patients with long COVID combined with coronary heart disease (CHD).<br><br>METHODS: This retrospective study included 89 patients with long COVID, who were divided into CHD group and non-CHD group. The clinical indexes such as maximum heart rate and oxygen saturation during cardiac rehabilitation were compared between the two groups of subjects. The 6-minute walk test (6-MWT), Pittsburgh Sleep Quality Index (PSQI), 7-item Generalized Anxiety Disorder Scale (GAD-7), Nicotine Dependence Detection Scale (FTND) and the Depression Screening Scale (PHQ-9) were administered to patients. The same measures were re-administered to the patients after 3 months to explore the long-term effects of cardiac rehabilitation therapy.<br><br>RESULTS: Before receiving treatment, the maximum heart rate, maximum diastolic blood pressure and minimum SpO2 of the CHD group were significantly lower than those of the non-CHD group. The maximum heart rate, maximum systolic blood pressure, and 6-MWT were significantly lower before treatment than those at three months for both groups of patients. The PSQI, GAD-7, PHQ-9, and FTND scores were significantly higher before treatment than those at three months for both groups of patients. Comparison of differences between the two groups before and after treatment revealed that the CHD group had significantly worse cardiovascular measurements after SARS-CoV-2 infection than the non-CHD group.<br><br>CONCLUSION: Patients with long COVID combined with CHD have more severe symptoms, especially for their cardiac function. Cardiac rehabilitation can effectively improve patients' symptoms, and has long-term effects.},
}
@article {pmid40776995,
year = {2025},
author = {Fomundam, H and Nyambi, H and Hyera, F and Motaze, NV},
title = {Impact of long COVID-19 on employees of the mining industry in South Africa: a cross-sectional study.},
journal = {The Pan African medical journal},
volume = {51},
number = {},
pages = {37},
pmid = {40776995},
issn = {1937-8688},
mesh = {Humans ; Cross-Sectional Studies ; South Africa/epidemiology ; *COVID-19/epidemiology ; *Mining ; Male ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Efficiency ; Prevalence ; Young Adult ; },
abstract = {INTRODUCTION: coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020, and most patients recover within a few days or weeks. However, some patients suffer from long COVID, which is characterized by prolonged symptoms of varying severity. Given the importance of the mining sector to the South African economy, it is critical to comprehend the impact of long COVID on the mining sector.<br><br>METHODS: we carried out a cross-sectional study that included data extraction from participant medical records and responses to study questionnaires. We used unique identifiers to anonymize participant information and match data from medical records to participant questionnaires.<br><br>RESULTS: data from 239 medical records and 362 questionnaires were provided by employees from three mines. About 7% of people with COVID-19 were identified as having long COVID. In addition, there was no difference in productivity between people with and without long COVID.<br><br>CONCLUSION: our findings are not generalizable to the entire mining sector due to the limited number of participants who provided data. Additional studies that include a larger sample size are required to obtain more robust estimates of the prevalence of long COVID in the mining industry and explore potential effects of various treatment interventions for patients with long COVID.},
}
@article {pmid40776719,
year = {2026},
author = {Venkatachalam, M and Ramachandran, A and Duraisamy, A},
title = {Evaluating the efficacy of pain apprehension re-activation of movement (PARAM) using virtual reality for kinesiophobia among silk weavers with long COVID symptoms.},
journal = {Work (Reading, Mass.)},
volume = {83},
number = {1},
pages = {212-218},
doi = {10.1177/10519815251365087},
pmid = {40776719},
issn = {1875-9270},
mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; Adult ; *Phobic Disorders/therapy/psychology ; India ; SARS-CoV-2 ; *Virtual Reality ; Pain Measurement/methods ; Quality of Life/psychology ; *Exercise Therapy/methods ; Kinesiophobia ; },
abstract = {BackgroundWeaving is a key livelihood in Erode, Tamil Nadu. Long COVID-19 symptoms, especially kinesiophobia, hinder weavers' ability to work, necessitating better interventions.ObjectiveTo study the impact of Pain Apprehension Re-Activation of Movement (PARAM) VR intervention compared to conventional exercises in mitigating kinesiophobia among the target population.MethodsA quasi-experimental design involved 84 silk weavers from southern India divided into Ex-Groups (n = 42) that received conventional exercises and VR-Group (n = 42) that received the same set of exercises in virtual ambience in PARAM protocol which is a novel approach where the patient compares video graphs taken in virtual ambience with physical environment for self-realization on their movement capacity. Totally 48 males and 36 females participated, with an average age of 45.2 (4.7). Tampa Scale for Kinesiophobia (TSK), Visual Analogue Scale (VAS) for pain, and SF-12 scale for health-related quality of life were used at baseline, after two weeks and at the end of the 4 weeks of intervention.ResultsBoth groups showed significant improvements (VR-Group- TSK:χ[2 ]= 18.42, p < 0.001;VAS:χ[2 ]= 16.21, p < 0.001;SF-12:χ[2 ]= 19.55, p < 0.001 and Ex-Group TSK:χ[2 ]= 10.67, p = 0.005, VAS:χ[2 ]= 8.49, p = 0.014, SF-12:χ[2 ]= 12.34, p = 0.002). Improvement in the VR-Group was immediate and consistently better than the Ex-group. (Post-test-1, TSK:U = 45, p = 0.002; VAS: U = 50.5, p = 0.004; SF-12: U = 42, p = 0.001, Post-test-2-TSK: U = 60, p = 0.048; VAS: U = 65.5, p = 0.036; SF-12: U = 58, p = 0.044).ConclusionPARAM and conventional exercises were effective in reducing apprehension to movement among silk weavers with long-term COVID-19. However, PARAM training resulted in a significantly better improvement that was faster and more consistent.},
}
@article {pmid40772993,
year = {2025},
author = {Siqueira, IFB and Figueiredo, LA and Fernandes, CEM and Cintra, LP and de Oliveira, GF and Rios, MA and Maciel, R and Ferretjans, R and Guimarães, NS and Magno, LAV},
title = {Metabolic brain changes in post-acute COVID-19: systematic review and meta-analysis of [18F]-FDG-PET findings.},
journal = {Brain structure &amp; function},
volume = {230},
number = {7},
pages = {128},
pmid = {40772993},
issn = {1863-2661},
mesh = {Humans ; *COVID-19/metabolism/diagnostic imaging/complications ; Positron-Emission Tomography/methods ; Fluorodeoxyglucose F18 ; *Brain/metabolism/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Radiopharmaceuticals ; Glucose/metabolism ; },
abstract = {Individuals with long COVID exhibit neurological and psychiatric symptoms that often persist well beyond the initial SARS-CoV-2 infection. Studies using [18F]-FDG positron emission tomography (FDG-PET) have revealed diverse abnormalities in brain glucose metabolism during the post-acute phase of COVID-19. We conducted a systematic review and meta-analysis to assess the spatial distribution and heterogeneity of brain metabolic changes in patients in the post-acute phase of COVID-19 relative to controls. We searched the MEDLINE, EMBASE, and CENTRAL databases in June 2025 for studies reporting FDG-PET data in patients with post-acute COVID-19 who have persistent neurological symptoms. Of the 14 eligible studies (584 scans), 13 reported glucose hypometabolism across frontoparietal regions, with the frontal cortex being the most consistently affected. This finding was confirmed by meta-analysis, which revealed a large and significant effect in the frontal cortex (Hedges' g = 1.34; 95% CI: 0.79-1.88; p < 0.001), despite high heterogeneity (I[2] = 93.6%). The systematic review indicates that brain metabolism generally improves over time, with widely varying recovery timelines, and consistently correlates hypometabolism with neurological symptom burden. These findings underscore the clinical relevance of frontoparietal hypometabolism in post-acute COVID-19 and its association with neurocognitive deficits, highlighting the need for longitudinal, quantitative PET studies to elucidate temporal dynamics and inform therapeutic development.},
}
@article {pmid40771985,
year = {2025},
author = {Wells, AM and Rolin, S and Robles-Ramamurthy, B and Gibson-Lopez, G and Goros, M and Gelfond, JA and Gelfond, S and Balfanz, P and Deuter, M and McGeary, D and Verduzco-Gutierrez, M},
title = {Neuropsychiatric symptoms cluster as primary drivers of Long COVID complexity: a South Texas retrospective cohort study.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1612489},
pmid = {40771985},
issn = {1664-2295},
support = {F30 MH134482/MH/NIMH NIH HHS/United States ; T32 GM113896/GM/NIGMS NIH HHS/United States ; T32 NS082145/NS/NINDS NIH HHS/United States ; T32 GM145432/GM/NIGMS NIH HHS/United States ; U18 HS029947/HS/AHRQ HHS/United States ; R25 NS089462/NS/NINDS NIH HHS/United States ; UM1 TR004538/TR/NCATS NIH HHS/United States ; },
abstract = {Long COVID, previously known as Post-Acute Sequelae of SARS-CoV-2 (PASC), refers to prolonged symptoms or diagnosable conditions following COVID-19 infection. The neuropsychiatric profile of Long COVID patients remains ambiguous. This study aimed to assess neuropsychiatric symptoms in a retrospective cohort of Long COVID patients (N = 162) at a Rehabilitation Medicine clinic in South Texas. Clinical data from patient records were used to calculate a Symptom Score, and screening tools for stress/PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and quality of life (SWL) were employed to evaluate if Long COVID duration and severity could predict neuropsychiatric outcomes. The majority were female (71%) and Hispanics (53%) who presented for treatment of Long COVID symptoms during the study period, including fatigue (93%), coughing/shortness of breath (81%), fever (67%), anosmia (58%), ageusia (54%), and weight loss (56%). A minority of participants were hospitalized (N = 49) or required ventilator support (N = 5) during acute infection. There was a high burden of neuropsychiatric symptoms, including subjective cognitive impairment (79%), headache (74%), and insomnia (58%). Symptom Score (median = 9, IQR [8,11]) was significantly correlated with increased depression (PHQ-9; p < 0.05), anxiety (GAD-7; p < 0.05) and elevated stress/PTSD (PCL-5; p < 0.05) symptoms. Long COVID patients taking stimulants or mood stabilizers had higher GAD-7 (p < 0.031, p < 0.035) and PHQ-9 (p < 0.034, p < 0.009) scores but not PCL-5 scores. Importantly, duration of Long COVID symptomatology also did not predict PCL-5 scores. No patient factors (e.g., sex, age, BMI, ethnicity) mediated Symptom Score. Nonetheless, historically marginalized groups, such as women and Hispanics, have been disproportionately affected by COVID-19. This study is the first to utilize validated screening tools to determine the presence and severity of neuropsychiatric symptoms in Long COVID patients. These findings may guide clinical management and future research on Long COVID, especially in historically excluded populations.},
}
@article {pmid40770070,
year = {2025},
author = {Boparai, MS and Gordon, J and Bajrami, S and Alamuri, T and Lee, R and Duong, TQ},
title = {Incidence and risk factors of new-onset hypertension up to 3 years post SARS-CoV-2 infection.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {28728},
pmid = {40770070},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/complications/epidemiology/virology ; *Hypertension/epidemiology/etiology ; Female ; Male ; Risk Factors ; Middle Aged ; Incidence ; Retrospective Studies ; Aged ; SARS-CoV-2/isolation &amp; purification ; Adult ; Hospitalization ; Comorbidity ; },
abstract = {COVID-19 can trigger new cardiovascular events, including hypertension, in the acute setting. However, few studies have reported sustained new-onset hypertension post-infection. Moreover, these studies have a small sample size, inadequate controls, and a short (< 1 year) follow-up time. This retrospective cohort study of 64,000 COVID-19 patients) from the Stony Brook Health System assessed the incidence and risk factors for new-onset hypertension after COVID-19. Contemporary COVID-negative controls were obtained and propensity-matched for age, race, sex, ethnicity, and major comorbidities before analyzing outcomes. The primary outcome was new-onset hypertension up to 3 years post-index date. About 9.93% of hospitalized patients and 4.66% of non-hospitalized patients developed new-onset hypertension after COVID-19. Hospitalized COVID-positive patients were more likely to develop hypertension compared to COVID-negative controls (Hazard Ratio [HR] = 1.57, 95% Confidence Interval [CI] [1.35-1.81]) and non-hospitalized COVID-positive controls (HR: 1.42, 95%CI [1.24-1.63]). Non-hospitalized COVID-positive patients were not more likely to develop hypertension than COVID-negative controls (HR: 1.05, 95%CI [0.98-1.13]). COVID-19 was one of the five greatest risk factors for developing hypertension. COVID-19 patients are at increased risk of developing hypertension beyond the acute phase of the disease compared to controls. Long-term follow-up, holistic workups, and vigilant blood pressure screening and/or monitoring for COVID-19 patients are needed.},
}
@article {pmid40769733,
year = {2025},
author = {Wilson, CM and Boright, LE and Henshaw, AM and Naccarato, A},
title = {Role of rehabilitation in palliative care after the COVID-19 pandemic: a narrative review.},
journal = {Annals of palliative medicine},
volume = {14},
number = {4},
pages = {379-392},
doi = {10.21037/apm-25-6},
pmid = {40769733},
issn = {2224-5839},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Palliative Care/organization &amp; administration ; Pandemics ; SARS-CoV-2 ; },
abstract = {BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic resulted in an historic disruption and transformation of the healthcare system, including the management of individuals with serious illness. Rehabilitation for patients facing serious or life-threatening illness is underutilized and poorly understood, resulting in unwarranted suffering, disability, and poorly coordinated care. This narrative review aims to describe the impact of the COVID-19 pandemic on the role and scope of rehabilitation within the context of serious illness and palliative care.<br><br>METHODS: A focused review of the literature included selected articles identified from three databases published from January 2020 to January 2025. Findings were synthesized narratively, with a focus on identifying themes and gaps in the literature related to two main topics: (I) the evidence related to rehabilitation for those with serious or life-threatening COVID-19 during the pandemic and (II) how rehabilitation for patients with serious illness has been transformed after emerging from the pandemic (including non-COVID diagnoses such as cancer, neurologic conditions, etc.).<br><br>KEY CONTENT AND FINDINGS: The key themes identified during the COVID-19 pandemic emphasized the need for early rehabilitation, interdisciplinary care, and an emphasis on cardiopulmonary principles for rehabilitation. Themes identified during the pandemic also included the emerging role of telerehabilitation, and need for evidence and clinical guidelines for serious illnesses (including long COVID). Themes related to the transformative effect on palliative rehabilitation after the pandemic included an increased importance and focus on coordination of care and interdisciplinary care for those with serious illness and increased focus on mental health and social determinants of health (SDOH). Additionally, there appears to be increased infrastructure and activity related to research, advocacy, and awareness for palliative rehabilitation.<br><br>CONCLUSIONS: The COVID-19 global pandemic highlighted the need for high quality, coordinated palliative care, including rehabilitation services, for patients facing a serious or life-threatening illness. Due to the benefits to a person's quality of life (QoL), dignity, and comfort, there is increasing evidence of the importance of seamless, ongoing access to rehabilitation services for patients with serious illness.},
}
@article {pmid40764982,
year = {2025},
author = {Guidry, JPD and Laestadius, LI and Burton, CW and Perrin, PB and Miller, CA and Pinto, MD and Stevens, MP and Chelimsky, T and Gharbo, R and Cuddeback, GS and Carlyle, KE},
title = {Staying Safe for the Long Haul: A Health Belief Model Analysis of COVID-19 Preventive Behaviors Through the Lens of Long COVID.},
journal = {Clinical nursing research},
volume = {34},
number = {6},
pages = {267-276},
pmid = {40764982},
issn = {1552-3799},
support = {K12 HD108269/HD/NICHD NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/prevention &amp; control/psychology ; Female ; *Health Belief Model ; Male ; Adult ; Middle Aged ; *Health Behavior ; SARS-CoV-2 ; United States ; *Health Knowledge, Attitudes, Practice ; Aged ; Surveys and Questionnaires ; },
abstract = {Health problems associated with post-acute COVID-19, also known as "Long COVID," range from mild to severe. The best defense against this potentially serious condition is to prevent COVID-19 infection and reinfection. The same preventive measures for COVID-19 may be used to help prevent the spread of Long COVID. This study used the Health Belief Model (HBM) to examine whether and how public understanding and awareness of Long COVID and its prevention shape the adoption of COVID-19 preventive behaviors. N = 605 English-speaking U.S.-based adults were recruited via Qualtrics. Predictors of intention to carry out COVID-19 preventive behaviors were investigated. Outcomes included behaviors relevant to preventing both acute and Long COVID. Across all models, except the one examining intent to get a vaccine booster, Black respondents were more likely than White respondents to express intent to carry out COVID-19 preventive behaviors. In addition, HBM constructs added significantly to the regression models. Susceptibility to Long COVID was significant for all behavioral outcomes (all ps < .05), self-efficacy for wearing a mask (p < .001), and self-efficacy for testing for COVID-19 after exposure and before a social event (ps < .001). In addition, perceived benefits for Long COVID prevention predicted intent of mask-wearing (p < .001), testing before a social event (p = .002), and getting a vaccine booster (p = .001). Perceived severity of Long COVID did not significantly predict adherence to preventive behaviors. U.S. adults are more likely to express intent to carry out COVID-19 preventive behaviors, such as masking and receiving booster vaccines, when they report feeling greater susceptibility to Long COVID as well as greater self-efficacy for engaging in these preventive behaviors. Public health messaging about Long COVID with incorporation of HBM constructs may be an effective means of increasing continued recommended COVID-19 preventive behaviors, which also hold co-benefits for prevention of infections, such as influenza and measles, as well as emerging viruses such as avian flu.},
}
@article {pmid40763841,
year = {2025},
author = {Wang, SS and Yuan, RL and Wang, WF and Peng, Y and Hu, KC and He, WB and Zhao, YX and Yan, X and Zhang, Z and Chu, SF and Chen, NH},
title = {Spike RBD drives sustained Parkinson's disease progression via microglia-neuron crosstalk-mediated RTP801 upregulation.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.07.060},
pmid = {40763841},
issn = {2090-1224},
abstract = {INTRODUCTION: Emerging evidence highlights the exacerbation and sustained Parkinson's disease (PD) progression following COVID-19. The SARS-CoV-2 spike receptor-binding domain (RBD), which can persist in the brain post-infection, is a likely contributor, but how it drives this neuropathology is unclear.<br><br>OBJECTIVES: To elucidate the underlying mechanisms of long COVID's impact on PD and identify mechanism that contribute to the continuous progression of PD.<br><br>METHODS: The SARS-CoV-2 spike RBD was stereotactically injected into the substantia nigra pars compacta of &#x3b1;-synuclein (&#x3b1;Syn) A53T mice within a chronic stress-genetic susceptibility model. We characterized the pathological impact of RBD using motor and non-motor behavioral tests, fMRI-based functional connectivity, in vivo electrophysiology, immunofluorescence, and &#x3b1;Syn aggregate analysis. To elucidate the underlying mechanisms, we then employed RNA-sequencing, transmission electron microscopy, microglial depletion, and comparative studies in &#x3b1;Syn A53T mice lacking RTP801 (&#x3b1;Syn A53T[+]; RTP801[-/-]).<br><br>RESULTS: RBD accelerated PD-related motor and non-motor symptom deterioration, impaired brain functional connectivity, and reduced neuronal excitability. It exacerbated dopaminergic neuron degeneration and &#x3b1;Syn aggregation. RTP801 was identified as a critical mediator of RBD-induced PD progression, with its sustained upregulation in dopaminergic neurons dependent on microglial activation. Mechanistically, initially activates microglia induced an increase in neuronal RTP801 via IL-6 and IL-8. RBD leaded to mitochondrial dysfunction, mtDNA release, and activation of the cGAS-STING pathway between neurons and microglia, triggering a mtDNA-cGAS-STING-IFN&#x3b2;/RTP801 feedback loop, driving neurodegeneration.<br><br>CONCLUSIONS: Our findings demonstrate that SARS-CoV-2 RBD exacerbates PD progression through a pathogenic crosstalk between microglia and neurons. This neurotoxic signaling is mediated by a mitochondrial mtDNA-cGAS-STING-IFN&#x3b2;/RTP801 axis. Targeting RTP801 or the STING pathway may therefore represent a promising therapeutic strategy to mitigate long COVID-associated progression of PD.},
}
@article {pmid40763524,
year = {2025},
author = {Lu, C and Ma, J and Qiao, Z and Yu, Y and Xu, W and Liu, W and Wang, F},
title = {Early-life indoor environmental exposures and COVID-19 outcomes in Chinese preschool children: A secondary analysis of a multicenter study.},
journal = {Journal of hazardous materials},
volume = {496},
number = {},
pages = {139445},
doi = {10.1016/j.jhazmat.2025.139445},
pmid = {40763524},
issn = {1873-3336},
mesh = {Child, Preschool ; Female ; Humans ; Infant ; Male ; *Air Pollution, Indoor/adverse effects ; China/epidemiology ; *COVID-19/epidemiology ; *Environmental Exposure/adverse effects ; Heating ; Ventilation ; East Asian People ; },
abstract = {BACKGROUND: Indoor environmental factors during early life may influence susceptibility to respiratory infections, but their relationship with COVID-19 outcomes in children and parents remains unclear.<br><br>OBJECTIVES: This study investigates associations between early-life household exposures (fuel type, heating methods, ventilation patterns, redecoration, dampness/mold, incense, and mosquito coil use) and COVID-19 infection and sequelae in children and their parents.<br><br>METHODS: We conducted a multicenter survey among 20,012 preschool children and their parents (total 60,036 participants) from nine cities in China between December 2019 and May 2023. Logistic regression models were applied, adjusting for sociodemographic and environmental covariates. Sensitivity analyses included adjustment for outdoor air pollutants and climatic factors.<br><br>RESULTS: Household factors such as solid fuel use, insufficient ventilation, and indoor dampness/mold were associated with higher odds of COVID-19 infection among children and parents. Use of mechanical ventilation and clean heating systems were associated with lower odds. Associations with long COVID (n&#x202f;=&#x202f;20 child cases) were exploratory and imprecise.<br><br>CONCLUSIONS: Indoor household exposures may influence COVID-19 outcomes in children and parents, independent of outdoor air pollution. These findings highlight the potential of improving indoor environments as a preventive measure, but longitudinal studies with clinical verification are needed.},
}
@article {pmid40762988,
year = {2025},
author = {Gusmão, ACS and Scaléa, ACR and Uehara, SCDSA},
title = {Symptoms of long COVID in children and adolescents: a scoping review.},
journal = {Revista da Escola de Enfermagem da U S P},
volume = {59},
number = {},
pages = {e20240435},
pmid = {40762988},
issn = {1980-220X},
mesh = {Humans ; Adolescent ; Child ; *COVID-19/complications/diagnosis/epidemiology/physiopathology ; Age Factors ; },
abstract = {OBJECTIVE: To map the symptoms of Long Covid (LC) presented by children and adolescents.<br><br>METHOD: This is a scoping review, using the search engines Web of Science, Scopus, Virtual Health Library, and PUBMED, following the principles of the Joanna Briggs Institute.<br><br>RESULTS: Sixteen studies were selected, which showed that fatigue, headache, dyspnea, and cough were the most frequent symptoms of LC. There is a tendency for the development of child-adolescent LC related to the increase in age range, and the correlation between LC and predominant sex proved to be inconclusive. The presence of comorbidities, such as obesity, respiratory, neurological and renal diseases, was the most reported and a study showed an association between Covid-19 vaccine protection and LC.<br><br>CONCLUSION: This review points to a plurality of symptomatic manifestations of LC in children and adolescents, changing according to age group and health history.},
}
@article {pmid40762975,
year = {2025},
author = {Anzalone, AJ and Krichevsky, S and Yoo, YJ and Wilkins, KJ and Alakwaa, F and Liu, F and Sakhuja, A and Saltz, JH and Han, Y and Zhu, RL and Setoguchi, S and Kane-Gill, SL and Mallipattu, SK and He, Y and Ellison, DH and Byrd, JB and Parikh, CR and Saran, R and Moffitt, RA and Koraishy, FM and , },
title = {The Association of Long COVID and CKD: Findings from the National Clinical Cohort Collaborative.},
journal = {Clinical journal of the American Society of Nephrology : CJASN},
volume = {20},
number = {10},
pages = {1323-1340},
pmid = {40762975},
issn = {1555-905X},
support = {U54 GM115458/GM/NIGMS NIH HHS/United States ; OTA OT2HL161847/HL/NHLBI NIH HHS/United States ; U54GM104942-05S2, U54GM115458/GM/NIGMS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; },
abstract = {KEY POINTS: Baseline CKD, even mild, is associated with a higher risk of long coronavirus disease (COVID) in patients with acute severe acute respiratory syndrome coronavirus infection. Among those without CKD at baseline, Long COVID is associated with a higher risk of developing new CKD and faster kidney function decline. Associations between Long COVID and CKD/kidney function decline persist after matching, adjustment, and accounting for the competing risk of death.<br><br>BACKGROUND: Among patients with acute coronavirus disease-19 (COVID-19), the association of CKD and Long COVID has not been reported in large multicenter cohorts.<br><br>METHODS: This study used data from 59 health care systems across the United States, in the National Clinical Cohort Collaborative COVID enclave, to analyze the relationship between CKD and Long COVID among adults diagnosed with acute COVID-19 between October 2021 and September 2023. We conducted two main analyses. First analysis: we tested if baseline CKD (eGFR <60 ml/min per 1.73 m[2] or diagnostic code) or baseline ESKD are risk factors for Long COVID (identified using ICD-10-CM code U09.9). We secondarily assessed associations between baseline mild CKD (Stage 3a, eGFR 45&#x2013;59 ml/min per 1.73 m[2]) and Long COVID. Second Analysis: among patients without baseline CKD/ESKD, we examined if incident CKD/ESKD and eGFR decline (&#x2265;20% in 1 year) were associated with Long COVID. We used propensity score matching for demographics and data contributing site, with models adjusted for risk factors and competing risk of death. All outcomes were evaluated within a 365-day follow-up period from the onset of acute COVID-19.<br><br>RESULTS: First analysis: From an unmatched cohort of 2,385,20 patients with acute COVID-19, those with baseline CKD/ESKD had a higher risk of Long COVID (adjusted subdistribution hazard ratio [sHR], 1.13; 95% confidence interval [CI], 1.09 to 1.18) after matching. A similar risk was noted even among those with mild CKD (sHR, 1.15; 95% CI, 1.05 to 1.25). Second Analysis: Among patients with acute COVID-19 and without baseline CKD/ESKD, Long COVID was associated with incident CKD/ESKD (sHR, 1.65; 95% CI, 1.51 to 1.81) and 20% or greater eGFR decline (sHR, 1.21; 95% CI 1.04 to 1.40) within 1 year.<br><br>CONCLUSIONS: CKD, even mild, was associated with an higher risk of Long COVID. Among those without baseline CKD, Long COVID was associated with incident CKD and eGFR decline.},
}
@article {pmid40761857,
year = {2025},
author = {Ono, R and Takayama, S and Arita, R and Ishizawa, K and Kikuchi, A and Abe, M and Ohsawa, M and Saito, N and Kanno, T and Onodera, K and Ishii, T},
title = {Effectiveness of Japanese traditional medicine (Kamikihito and Saikokeishito) for treating long COVID: a prospective observational study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1609812},
pmid = {40761857},
issn = {2296-858X},
abstract = {BACKGROUND: Long COVID symptoms, especially brain fog, significantly impair patient quality of life (QOL); however, effective treatments remain elusive. Japanese traditional medicine (JTM, usually called Kampo medicine) is often used adjunctively to treat patients with diverse manifestations of long COVID.<br><br>OBJECTIVE: To evaluate the effectiveness of JTM in treating long COVID using a comprehensive QOL assessment.<br><br>METHODS: This single-center, prospective observational study evaluated QOL changes in patients with symptoms persisting beyond 28 days from the onset of COVID-19 (long COVID) who visited our general medicine outpatient department between October 2021 and August 2024. The treatment plan was determined by the attending physician based on the patient's condition. The health-related QOL (HR-QOL) was comprehensively assessed using EuroQol-5 demensions-5levels (EQ-5D-5L) scores (ranging from -0.025 to 1.000, with higher values indicating better HR-QOL) at baseline and 3 months after the first visit. The formulations and factors associated with QOL changes were analyzed using multivariate logistic regression analyses.<br><br>RESULTS: We analyzed 112 patients. The most common symptoms were fatigue (83.9%). The median (interquartile range) HR-QOL of the entire cohort significantly increased from 0.711 (0.561-0.711) at baseline to 0.833 (0.671-0.890) at 3 months (p < 0.0001); the proportion of patients exceeding the national standard significantly increased from 7.1% to 20.4% (p = 0.0037). The brain fog patients group (50.0%, N = 56), the median (interquartile range) HR-QOL of the entire cohort significantly increased from 0.677 (0.551-0.770) at baseline to 0.750 (0.623-0.846) at 3 months (p < 0.005). However, the proportion of patients achieving the Japanese average HR-QOL did not show improvement significantly. A total of 101 patients (90.2%) were treated with JTM, and a combination of kamikihito and saikokeishito was administered to 20 patients. Multivariate regression analysis revealed that the combination usage was associated with greater improvements in the HR-QOL in all patients (odds ratio 5.4) and brain fog patients' group (odds ratio 6.1).<br><br>CONCLUSION: Long COVID treatment involving JTM improved the patients' QOL at 3 months. The combination of kamikihito with saikokeishito may be a potential treatment option for long COVID. However, a randomized controlled trial is required to confirm its efficacy.},
}
@article {pmid40761637,
year = {2025},
author = {Huff, HV and Villanueva-Colina, C and Diaz, MM and Tovar, S and Davila Luna, A and Wu, T and Hamer, DH and Koralnik, IJ and Solomon, T and Caniza, MA and Garcia, PJ},
title = {Neurologic symptoms following COVID-19 in Lima, Peru: a prospective longitudinal observational study.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1524613},
pmid = {40761637},
issn = {1664-2295},
support = {D43 TW010543/TW/FIC NIH HHS/United States ; HHSN272201400006C/AI/NIAID NIH HHS/United States ; },
abstract = {INTRODUCTION: There is limited research on long-term neurologic symptoms following SARS-CoV-2 infection in Peru. This study aimed to describe the longitudinal experience of survivors of mild to moderate COVID-19 in Lima, Peru.<br><br>METHODS: This prospective, longitudinal observational study included neurologic follow-up data between 3- and 12-months following SARS-CoV-2 infection. Recruitment to a parent study: "Natural History of SARS-CoV-2 in Comparison to Influenza Virus: A Multi-site Study Focused on the Southern Hemisphere and Equatorial Regions" (COFLU Peru), occurred between February 2021 and February 2022 in a Callao, Peru public hospital emergency department. In-person visits for this sub-study, "Neuro COFLU," included neurologic history and symptom questionnaire.<br><br>RESULTS: Fifty-four patients were seen for at least one visit, two of whom required hospitalization for COVID-19. Forty-one (76%) reported at least one pre-existing neurologic diagnosis (59% headaches; 24% migraines). At follow-up visits, patients reported at least one new neurologic symptom since COVID-19: 24/29 (83%) at 90&#x202f;days, 31/42 (74%) at 180&#x202f;days, 41/46 (89%) at 270&#x202f;days, and 20/21 (95%) at 365&#x202f;days. The median number of new symptoms was 3 at 90&#x202f;days, 3 at 180, 4 at 270 and 3 at 365&#x202f;days. Days 90-180 frequent symptoms included: muscular pain, neck stiffness, headache, loss of appetite, numbness, insomnia, and weakness (24-31%). Days 181-365 frequent symptoms included: fatigue, weakness, memory problems, irritability, changes in hearing, muscular pain, joint pain, and insomnia (28-33%). Pre-existing anxiety was associated with post-COVID-19 hearing changes, muscular pain, numbness and weakness and pre-existing depression with neck stiffness and numbness. No significant association was found with age, sex, vaccination status, or pre-existing headaches. Full recovery was reported for 6/29 (21%) at day 90, 13/42 (31%) at day 180, 17/46 (37%) at day 270, and 9/20 (45%) at day 365. By day 365, patients reported median recovery of 85-90%.<br><br>DISCUSSION: Persistent neurological symptoms are common in COVID-19 survivors in Lima. Many new neurologic symptoms persisted and increased in prevalence over 3-12&#x202f;months. Limitations include lack of control group and small sample size. Longitudinal studies of outcomes are needed to predict and mitigate the long-term physical, social and economic effects of SARS-CoV-2 infection.},
}
@article {pmid40761366,
year = {2025},
author = {Clapp, A and Zapp, D and DeLuca, T and Morris, A and Yong, SJ and Ahmad, R and Munipalli, B},
title = {Abnormal uterine bleeding and fertility challenges secondary to long COVID: A case report.},
journal = {SAGE open medical case reports},
volume = {13},
number = {},
pages = {2050313X251364093},
pmid = {40761366},
issn = {2050-313X},
abstract = {Menstrual irregularities and abnormal uterine bleeding have been increasingly reported following severe acute respiratory syndrome coronavirus 2 infection, likely due to viral-induced endocrine disruption and immune dysregulation. A woman in her late 30s, with previously regular menses, developed persistent abnormal uterine bleeding after recovering from coronavirus disease 2019. Lab work-up over the next 2 years demonstrated high follicle-stimulating hormone, low anti-Müllerian hormone, low estrogen, and borderline antinuclear antibody titers. A pelvic ultrasound showed low antral follicle count, and she had challenges with fertility preservation. The patient was suspected of having an exaggerated immune reaction to severe acute respiratory syndrome coronavirus 2 infection with her strong family history of autoimmune disease and borderline antinuclear antibody, which may have led to an autoimmune-induced premature ovarian insufficiency. This case highlights the need to recognize post-viral menstrual irregularities and endocrine dysfunction as a potential consequence of coronavirus disease 2019. Clinicians should consider postinfectious endocrine disturbances in patients with new-onset abnormal uterine bleeding or infertility and evaluate for immune-mediated mechanisms when appropriate. Further research is needed to elucidate the long-term impact of coronavirus disease 2019 on reproductive health.},
}
@article {pmid40761360,
year = {2025},
author = {McCormick, S and Cukic, I and Alexanders, J and Yeowell, G and Fatoye, F and Kelly, BM and Fitzgerald, V and Cable, T and Doherty, P and Deniszczyc, D and Michael, P},
title = {Exercise professionals in extended scope of practice roles: a qualitative exploration of a new model of rehabilitation.},
journal = {BMJ public health},
volume = {3},
number = {2},
pages = {e002322},
pmid = {40761360},
issn = {2753-4294},
abstract = {BACKGROUND: There is a need to provide greater patient choice through accessible and sustainable rehabilitation for people with long-term conditions. New models of rehabilitation employing non-clinical healthcare workers in extended service practice roles are developing. Little research has investigated the experiences of non-clinical health workers, such as exercise professionals, in extended scope of practice roles. This research explored the experiences of stakeholders and beneficiaries (exercise professionals in extended scope of practice roles, allied health professionals and people with Long COVID) participating in a new model of rehabilitation delivered online from selected Fitness and Well-being Centres of a UK charity.<br><br>METHODS: A qualitative design using in-depth semistructured interviews was undertaken to explore the experiences of triage physiotherapists, specialist trained exercise professionals, referred to as rehabilitation specialists and people with Long COVID participating in the new model of rehabilitation involving exercise, education and well-being support.<br><br>RESULTS: Five triage physiotherapists, two rehabilitation specialists and three people with Long COVID were recruited. Facilitators, barriers and opportunities were identified as key themes. Facilitators related to 'it isn't just exercise', 'condition specific needs are met' and 'dedicated team who make a difference'. Barriers related to 'supporting staff training needs' and 'optimising resources/mode of delivery for clinical population'. Opportunities related to the provision of a 'stepped-down approach at programme end', 'building and developing the team', and 'identifying and evaluating emerging trends through process evluations'.<br><br>CONCLUSIONS: This novel model of rehabilitation provided positive experiences for people living with Long COVID. Some aspects of the role provided job satisfaction for the delivery team but mentorship, support and additional training in psychological skills and mental health are important when considering sustainability and expansion of the programme. Scaling out to other clinical populations and areas where access to conventional services is sparse could provide a viable public health strategy to improve access to services, thereby reducing mainstream healthcare costs.},
}
@article {pmid40760951,
year = {2025},
author = {Tsuchiya, H},
title = {Author's Reply "Could Long COVID Oral Symptoms and COVID19 Vaccination Oral Side Effects Be Induced by the Spike Protein?".},
journal = {Oral diseases},
volume = {},
number = {},
pages = {},
doi = {10.1111/odi.70052},
pmid = {40760951},
issn = {1601-0825},
support = {20K10152//JSPS KAKENHI/ ; },
}
@article {pmid40760948,
year = {2025},
author = {Santana, LADM and Floresta, LG and Santos, GA and da Fonte, JBM and Borges, LP},
title = {Comment on: "Could Long COVID Oral Symptoms and COVID-19 Vaccination Oral Side Effects be Induced by the Spike Protein?".},
journal = {Oral diseases},
volume = {},
number = {},
pages = {},
doi = {10.1111/odi.70056},
pmid = {40760948},
issn = {1601-0825},
}
@article {pmid40760815,
year = {2025},
author = {Salazar, DA and Bhandari, D and Waiba, N and Pedapati, S and Adhikari, G},
title = {Pauci-immune glomerulonephritis: Post-COVID kidney disease continues to reappear, a case report.},
journal = {Science progress},
volume = {108},
number = {3},
pages = {368504251364950},
pmid = {40760815},
issn = {2047-7163},
mesh = {Humans ; Female ; *COVID-19/complications/immunology ; *Glomerulonephritis/drug therapy/immunology/pathology/etiology/diagnosis ; Aged ; SARS-CoV-2 ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Rituximab/therapeutic use ; Peroxidase/immunology ; Kidney/pathology ; Adrenal Cortex Hormones/therapeutic use ; },
abstract = {We present a female in her mid-70s with COVID-19 infection who developed worsening renal function along with systemic symptoms over months. The patient was initially monitored for long COVID and was referred to the nephrologist after she was found to have further worsening of her renal function. She underwent a renal biopsy and findings on light microscopy, immunofluorescence, and electron microscopy were consistent with crescentic glomerulonephritis, pauci-immune type with chronicity, and acute interstitial nephritis. These findings and a positive anti-neutrophilic cytoplasmic antibody immunofluorescence assay (ANCA IFA) and myeloperoxidase antibody confirmed myeloperoxidase-ANCA-positive pauci-immune glomerulonephritis. The patient was started on treatment with corticosteroids and Rituximab, resulting in improvement in her symptoms and renal function.},
}
@article {pmid40759992,
year = {2025},
author = {van Berkel, J and Lalieu, RC and Joseph, D and Hellemons, M and Lansdorp, CA},
title = {Hyperbaric oxygen therapy for long COVID: a prospective registry.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {28351},
pmid = {40759992},
issn = {2045-2322},
mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *COVID-19/therapy ; Registries ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Adult ; Patient Reported Outcome Measures ; Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; Surveys and Questionnaires ; },
abstract = {A potential beneficial effect of hyperbaric oxygen therapy (HBOT) on complaints of long COVID was found, leading to increased demand for this treatment despite many remaining clinical questions and lack of formal guideline recommendations and reimbursement. A registry was set up in order to gain more insight into patient characteristics and (long-term) outcomes of long COVID patients undergoing HBOT. Patient-reported outcome measures were collected at baseline, after treatment, at 3-month and 1-year follow up. This publication includes the 3-month results. The primary outcome measures were the mental and physical component score (MCS/PCS) of the SF-36 questionnaire. A clinically relevant positive or negative response was defined as a ≥ 10 point increase or decrease of in MCS and/or PCS after 3 months. Secondary outcomes included the EQ-5D, severity of complaints and ability to work. In this prospective registry, 56-63% of long term-ill patients had a clinically relevant improvement in MCS/PCS 3 months after HBOT. However, 13-19% of the patients had a clinically relevant deterioration in MCS/PCS. Symptoms that showed most improvement were predominantly in the cognitive domain. This indicates that HBOT may have a positive effect on complaints of long COVID, but alertness for worsening of the condition should be exercised.},
}
@article {pmid40758540,
year = {2026},
author = {Zajacova, A and Grol-Prokopczyk, H and Nahin, RL},
title = {Pain among US adults before, during, and after the COVID-19 pandemic: a study using the 2019 to 2023 National Health Interview Survey.},
journal = {Pain},
volume = {167},
number = {1},
pages = {142-149},
pmid = {40758540},
issn = {1872-6623},
support = {R01 AG065351/AG/NIA NIH HHS/United States ; Insight Grant 435-2021-0733//Federation for the Humanities and Social Sciences/ ; R01AG065351/AG/NIA NIH HHS/United States ; R01AG065351/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology ; Adult ; Male ; Female ; Middle Aged ; United States/epidemiology ; Health Surveys ; Aged ; *Chronic Pain/epidemiology ; Prevalence ; Young Adult ; Cross-Sectional Studies ; Adolescent ; Pandemics ; },
abstract = {The unprecedented disruption of the COVID-19 pandemic raises crucial questions about its impact on chronic pain levels in the US population. We present a comprehensive analysis of chronic pain (CP), high-impact chronic pain (HICP), and site-specific pain prevalence before, during, and after the pandemic, and investigate key contributing factors. We analyze a nationally representative sample of 90,769 community-dwelling adults aged 18 years and older from 3 cross-sectional waves of the National Health Interview Survey (2019, 2021, and 2023). Outcomes are CP and HICP; we also present findings for 6 site-specific pain measures. We include an extensive range of covariates (demographics, socioeconomic status, health behaviors, health conditions, mental health, and health insurance type); additional analyses also explore the role of long COVID. Chronic pain prevalence increased from 20.5% (95% confidence interval: 19.9%-21.2%) in 2019 to 20.9% (20.3%-21.6%) in 2021 and 24.3% (23.7%-25.0%) in 2023, representing an 18% increase over the study period. High-impact chronic pain prevalence, which was 7.5% (7.1%-7.8%) in 2019, declined to 6.9% (6.6%-7.3%) in 2021 before rising to 8.5% (8.1%-8.9%) in 2023, a 13% overall increase. The 2023 pain increases were widespread: they occurred for all examined body sites except tooth/jaw pain and all population subgroups. Long COVID accounted for approximately 13% of the observed 2019 to 2023 increase in both CP and HICP. In 2023, an estimated 60 million Americans experienced CP and 21 million experienced HICP, the highest prevalence ever recorded in the National Health Interview Survey. These findings suggest a significant escalation in the population burden of pain, with crucial implications for public health policy.},
}
@article {pmid40758213,
year = {2025},
author = {Rachid Zaim, S and Castillo, JD and Cabrera, A and Sankary, K and Ramirez, G and Li, XJ and Morales, LS},
title = {Long COVID among Latino Patients of Two Federally Qualified Health Centers in Washington State.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-09732-y},
pmid = {40758213},
issn = {1525-1497},
support = {1U18HS029905-01/HS/AHRQ HHS/United States ; },
}
@article {pmid40757708,
year = {2024},
author = {Fiorani, F and Moretti, G and Cerquiglini, L and Gizzi, C and Gizzi, G and Signorelli, P and Cataldi, S and Beccari, T and Delvecchio, E and Mazzeschi, C and Troiani, S and Albi, E},
title = {Relationship Between Plasma Acid Sphingomyelinase and Alteration in Taste and Smell as Indicator of Long COVID in Pregnant Women.},
journal = {Reports (MDPI)},
volume = {7},
number = {4},
pages = {},
pmid = {40757708},
issn = {2571-841X},
support = {20418 (2021.0348)//Fondazione Cassa di Risparmio/ ; },
abstract = {Background: Persistent alterations in taste and smell affect a significant proportion of individuals following COVID-19, representing a component of post-acute COVID-19 syndrome, commonly referred to as long COVID. The degradation of sphingomyelin by acid sphingomyelinase is regarded as a biomarker for acquired demyelinating neuropathies. Objectives: This study was aimed to enroll women who contracted COVID-19 during pregnancy and experienced persistent alterations in taste and/or smell for more than 1 year post-infection, in comparison to pregnant women without any disturbances in these senses. Methods: The patients were subjected to a questionnaire investigating smell and taste disorders more than 1 year after the infection. Then, the levels of acid sphingomyelinase in the plasma of the participants were assessed. Results: The results showed that in women who had been pregnant and who had been infected with SARS Cov-2 during the COVID period and who still had taste and smell disorders 1 year later, plasma acid sphingomyelinase levels were double that of pregnant women who had contracted the infection during the COVID period but had not reported taste and smell disorders and that of pregnant women analyzed after the COVID period. Conclusions: The results suggest a hypothesis that the persistence of sensory disturbances in long COVID was probably due to a failure to utilize brain circuitry with demyelination resulting from chemosensory dysfunction of the olfactory epithelium.},
}
@article {pmid40757370,
year = {2025},
author = {Vernon, SD and Rond, C and Bell, J and Butler, B and Isolampi, S and Otteson, A and Phalwane, P and Mower, S and Roundy, S and Kaufman, DL and Cash, AB and Bateman, L},
title = {REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1627462},
pmid = {40757370},
issn = {1662-4548},
abstract = {BACKGROUND: Long COVID is characterized by fatigue, cognitive dysfunction, and other persistent symptoms. This randomized, double-blind, controlled trial evaluated the efficacy of oral oxaloacetate (OAA) in improving fatigue and cognitive function in adults with long COVID.<br><br>METHODS: A total of 69 participants were randomized to receive either 2,000&#x202f;mg/day of OAA or the control for 42&#x202f;days. The primary outcome was fatigue reduction, measured by the Chalder Fatigue Questionnaire (CFQ). The secondary and exploratory outcomes included the DePaul Symptom Questionnaire Short Form (DSQ-SF), health-related quality of life (RAND-36), cognitive function (Defense Automated Neurobehavioral Assessment (DANA) Brain Vital), and time upright (UP Time).<br><br>RESULTS: No significant difference in the CFQ-measured fatigue reduction was observed between the groups. However, the OAA group showed significantly greater improvements in the DSQ-SF-measured fatigue and total symptom burden at day 21 of the trial. Cognitive performance improved significantly in the OAA group, with strong correlations between symptom response and cognitive gains. OAA was well tolerated.<br><br>CONCLUSION: OAA may contribute to earlier improvements in symptom burden and cognitive function in individuals with long COVID. Further studies are warranted.},
}
@article {pmid40757253,
year = {2025},
author = {Sliwa, K and Singh, K and Nikhare, K and Kondal, D and Raspail, L and Jain, M and Akter, S and Talukder, SH and Kato, T and Bertagnolio, S and Rylance, J and Banerjee, A and Narula, J and Pineiro, D and Perel, P and Prabhakaran, D and , },
title = {Long COVID Syndrome, Mortality and Morbidity in Patients Hospitalized with COVID-19 From 16 Countries: The World Heart Federation Global COVID-19 Study.},
journal = {Global heart},
volume = {20},
number = {1},
pages = {66},
pmid = {40757253},
issn = {2211-8179},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Cardiovascular Diseases/epidemiology ; *COVID-19/complications/mortality/epidemiology ; Global Health ; *Hospitalization/statistics &amp; numerical data ; Incidence ; Morbidity/trends ; *Post-Acute COVID-19 Syndrome/epidemiology ; Quality of Life ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long-term adverse consequences of the COVID-19 infection affect many organ systems, which requires comprehensive understanding of the disease burden and determinants of persistent long COVID-19 symptoms in diverse population. However, data on long COVID complications are sparse, particularly from low- and middle-income countries (LMICs). The World Heart Federation (WHF) global study assessed the incidence of vascular complications, persistent long COVID symptoms and factors associated with mortality and major adverse cardiovascular events (MACE) among patients with COVID-19 up to one year after hospitalization.<br><br>METHODS: We recruited a total of 2535 patients hospitalized with COVID-19 and followed up to one-year post-hospital discharge. We collected data on long COVID symptoms, quality of life, and clinical outcomes, including new onset diseases, MACE, and mortality at 1-, 3-, 6-, and 9-12 months post-discharge. Descriptive and generalized estimating equation (GEE) regression analysis was performed to assess the factors associated with mortality and MACE.<br><br>FINDINGS: The majority of participants were recruited from LMICs (64%) and male (56%) with a mean (SD) age of 59.5 (20.0) years. Among those tested for COVID-19 strain (52%), Omicron strain was the most prevalent (98%). The follow-up rate at one year was 90%. Over half of the participants (56%) reported experiencing at least one major long COVID symptom (fatigue, breathlessness, anxiety, chest pain, and palpitations) at 1-month, and one-quarter participants reported persistent long COVID symptoms at 9-12 months. On the EQ-5D scale, 49% reported difficulties in usual activities, 33% reported anxiety/depression, and 23% reported problems in mobility within the first 6 months. The most frequent new-onset illnesses were pulmonary embolism (8%), kidney disease (4%), and hypertension (3%). The cumulative all-cause mortality rate was 15% (n = 382) at one-year post-discharge. Long COVID symptoms were more common among females, individuals with pre-existing comorbidities, and those with more severe acute illness. Age, obesity, ICU admission, and underlying cardiovascular or pulmonary disease were associated with increased risk of mortality and MACE.<br><br>CONCLUSION: The study showed a substantial burden of mortality and morbidity, and a quarter of patients reported at least one persistent long COVID symptom after one year. Our findings underscore the need for early identification and management of long COVID symptoms in LMICs.},
}
@article {pmid40755628,
year = {2025},
author = {Tuttle, JJ and Scarboro, SD and Harper Iii, CA and Lind, T and Young, RC},
title = {Presumed Posterior Scleritis Complicated by Serous Retinal Detachment as a Possible Late Manifestation of COVID-19 Infection: A Pediatric Case Report.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e87284},
pmid = {40755628},
issn = {2168-8184},
abstract = {A wide range of systemic and ocular symptoms have been associated with 2019 novel coronavirus (COVID-19) infection, including long-term alterations in inflammatory pathways. We describe a novel case of an 11-year-old female presenting with posterior scleritis and associated serous retinal detachment, occurring one year after confirmed COVID-19 infection. The patient presented with a one-day history of central scotoma following three days of progressive right eye pain, photophobia, conjunctival injection, and blurred vision. She reported two prior episodes of right eye pain, the first of which occurred in the setting of acute COVID-19 infection. Examination revealed clinical signs of posterior scleritis with serous retinal detachment. Laboratory work-up for infectious and autoimmune etiologies was unremarkable. The patient was treated with topical corticosteroids and nonsteroidal anti-inflammatory therapy, resulting in complete resolution of symptoms and restoration of visual acuity. Despite the atypical response, posterior scleritis remains the presumed diagnosis based on recurrent episodes and clinical findings. The temporal association with initial COVID-19 infection raises the possibility of an etiological role, though it remains unclear whether persistent viral antigens or a dysregulated immune response underlie the condition. This case introduces posterior scleritis as a potential delayed ocular manifestation of COVID-19 infection and highlights the need for further research into post-viral inflammatory responses affecting the eye. For clinicians, it emphasizes the importance of considering recent or remote COVID-19 infection in the differential diagnosis of posterior segment inflammation.},
}
@article {pmid40755239,
year = {2025},
author = {Alhudiri, IM and Gaballa, MF and Ebrahim, FO and Ahire, KD and Eltaib, FI and Attitalla, IH and Elzagheid, AI},
title = {Post-Acute COVID-19 Pathophysiology: Cellular Stress Responses, Immune Dysregulation, and Biochemical Signatures in Recovery Phase.},
journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology},
volume = {59},
number = {4},
pages = {485-495},
doi = {10.33594/000000795},
pmid = {40755239},
issn = {1421-9778},
mesh = {Humans ; *COVID-19/immunology/physiopathology/pathology/blood ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; Biomarkers/blood ; SARS-CoV-2 ; Oxidative Stress ; Post-Acute COVID-19 Syndrome ; Endoplasmic Reticulum Stress ; Aged ; Cytokines/blood ; Interleukin-6/blood ; Endoplasmic Reticulum Chaperone BiP ; C-Reactive Protein/analysis ; },
abstract = {BACKGROUND/AIMS: Post-acute COVID-19 syndrome (PACS) presents with persistent symptoms such as fatigue, dyspnea, and cognitive impairment, even after apparent clinical recovery. Although widely reported, the biological basis of these symptoms remains unclear. This study aimed to investigate the underlying cellular, immunological, oxidative, and biochemical disturbances during the recovery phase of COVID-19 and evaluate their association with clinical symptomatology.<br><br>METHODS: A cross-sectional observational study was conducted involving 120 participants who were previously SARS-CoV-2 positive, recruited &#x2265;30 days post-recovery. Peripheral blood samples were analyzed for ER stress markers (HSP70, CHOP, GRP78), Pro- and anti-inflammatory cytokines (IL-6, TNF-&#x3b1;, IFN-&#x3b3;, IL-10), oxidative biomarkers (MDA, SOD, GSH), and biochemical parameters (ALT, AST, CRP, ferritin). T cell subsets were evaluated via flow cytometry. Statistical comparisons and correlation analyses were performed using SPSS v22.0.<br><br>RESULTS: Significant elevations were observed in all stress and inflammatory markers (p < 0.05). IL-6, CRP, and MDA showed strong positive correlations with fatigue and dyspnea scores. Treg percentages were reduced, and males exhibited higher biomarker levels than females. Persistent immune and oxidative activation was evident in the recovery phase.<br><br>CONCLUSION: Post-acute COVID-19 is associated with quantifiable cellular and molecular disturbances. This integrated analysis of ER stress, immune dysregulation, and oxidative imbalance provides a novel and comprehensive view of long COVID pathophysiology.},
}
@article {pmid40755156,
year = {2025},
author = {Harris, SRS and Sewell, B and Busse-Morris, M and Edwards, A and Jones, F and Leggat, F and Pallman, P and Fitzsimmons, D},
title = {Cost-Effectiveness of a Personalised Self-Management Intervention for People Living With Long Covid: The LISTEN Randomised Controlled Trial.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70357},
pmid = {40755156},
issn = {1369-7625},
support = {//This trial was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (COV-LT2-0009)./ ; },
mesh = {Humans ; Cost-Benefit Analysis ; *COVID-19/therapy/economics ; *Self-Management/methods/economics ; Male ; Female ; Middle Aged ; United Kingdom ; Aged ; Quality-Adjusted Life Years ; State Medicine ; Quality of Life ; SARS-CoV-2 ; Adult ; },
abstract = {BACKGROUND: In the United Kingdom, at least 1.9 million people are estimated to have experienced long Covid, of which 1.3 million have symptoms lasting for more than a year. The Long CovId Personalised Self-managemenT support EvaluatioN (LISTEN) trial evaluated the effectiveness and cost-effectiveness of a co-designed personalised self-management support intervention for non-hospitalised people living with long Covid.<br><br>METHODS: We conducted a pragmatic, multicentre, two-arm, parallel group and superiority randomised controlled trial for people who had experienced at least one long Covid symptom for 12 weeks or longer. A cost-utility analysis was undertaken alongside the LISTEN trial from both a UK National Health Service (NHS) and personal social services (PSS) and a societal perspective. Implementation costs were determined from study records, and quality of life and health and care resource use were collected by questionnaire at 6-week and 3-month follow-ups. Incremental net monetary benefit (INMB) analyses evaluated the cost-effectiveness of the intervention at a range of willingness-to-pay thresholds.<br><br>RESULTS: A total of 544 participants were included in the health economic analysis, of which 62.5% had complete data. The average cost of delivering the LISTEN intervention was &#xa3;846 per participant. At 3-month follow-up, mean quality-adjusted life years (QALYs) were 0.005 (95% CI -0.004 to 0.014) greater for participants receiving the LISTEN intervention compared to usual care. From the NHS and PSS perspective, total adjusted mean costs were &#xa3;491 (95% CI, &#xa3;128 to &#xa3;854) lower in the usual care arm. From the societal perspective, participants in the usual care arm lost more hours of work and usual activities and received more informal care, with the LISTEN intervention dominating usual care.<br><br>CONCLUSIONS: At accepted UK thresholds, the LISTEN intervention was not cost-effective from an NHS and PSS perspective, but it was found to be cost-effective from a societal perspective due to the impact of long Covid on work, informal care and usual activities. Further research is required to understand the costs and benefits of self-management support for longer-term horizons.<br><br>We are grateful for the contributions of the LISTEN Public and Patient Involvement and Engagement group comprising seven people (Anne Domeney, Ian Patel, Carol Rowe, Judith Parsons, Rebecca Beltran, Elizabeth Treadwell and Maria Ines de Sousa de Abreu) with long Covid who supported co-design, communications, trial recruitment and dissemination activities.<br><br>TRIAL REGISTRATION: ISRCTN36407216, registered 27 January 2022.},
}
@article {pmid40754877,
year = {2025},
author = {Nori, W and Hussein, ZA and Hamed, RM and Taha, M and Pantazi, AC},
title = {Bridging Gaps in Long COVID Therapy: A Mini Review.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673389691250709181809},
pmid = {40754877},
issn = {1875-533X},
abstract = {INTRODUCTION: Long COVID-19 (LC) is a condition that follows SARS-CoV- -2, an acute infection defined by persistent fatigue, dyspnea, and impaired cognitive function. LC presents a complex array that imposes ongoing challenges on global health, patients' quality of life, and functional capacity. Many inconsistencies surround its pathophysiology, diagnosis, prevention, and treatment. This review aims to cover missed gaps in LC with a special focus on therapeutic strategies concerning non-pharmacological, pharmacological, experimental, and innovative approaches for better patient management and outcomes, as well as to evaluate their effectiveness and guide future research.<br><br>METHODS: An online search was conducted using five digital repositories: PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library. A combination of keywords associated with LC therapy was employed: "long COVID, "pharmacological options," "non-pharmacological options," "innovative strategies," "experimental", and" quality of life (QOL)." Relevant data were extracted and synthesized to categorize therapeutic approaches into subtypes. A critical analysis was conducted on their mechanism of action, indication, outcome, and limitations.<br><br>RESULTS: The pooled prevalence of LC was 42%, and the symptom duration ranged from 3 months to 2 years. The most important risk factors for LC were female sex, unvaccinated status, and cases with co-morbidities. Diagnosis of LC was challenging due to a lack of diagnostic standardization and reliable biomarkers.<br><br>DISCUSSION: Non-pharmacological strategies were employed first, showing diverse efficacies; however, the reported literature was hindered by small sampling. Pharmacological agents show promising results but need further validation. Experimental and innovative strategies need longer studies and validations.<br><br>CONCLUSION: LC has imposed a significant burden on community health, necessitating the appropriate allocation of health resources and community support. Preventive and therapeutic interventions show promise, but the variability in patient response underscores the need for personalized approaches and more well-designed trials. Collaborative research and multi-disciplinary teams are needed to mitigate the long-term effects of LC and improve patient outcomes.},
}
@article {pmid40754870,
year = {2025},
author = {Groohi-Sardou, S and Dehghani, MM and Raesi, R and Hushmandi, K and Daneshi, S},
title = {Determining the Delayed Effects of COVID-19 in Children Hospitalized in Southeastern Iran from 2021 to 2023.},
journal = {Current pediatric reviews},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115733963373557250725053243},
pmid = {40754870},
issn = {1875-6336},
abstract = {INTRODUCTION: Understanding the delayed effects of COVID-19, often called "long COVID-19," is essential for creating effective treatment protocols and support systems for affected children. This study was conducted to determine the delayed effects of COVID-19 in hospitalized children.<br><br>METHODS: This cross-sectional study is descriptive-analytical and was conducted through a census of 137 hospitalized children diagnosed with COVID-19 in Jiroft, Iran, from 2021 to 2023. Data were collected using a checklist from the patients' medical records and through telephone interviews with the children's parents. The data were analyzed using descriptive and inferential statistics at a significance level of p < 0.05.<br><br>RESULTS: The average age of the children was 7.7 years, with a majority being boys, and a small percentage having underlying medical conditions. Most children were hospitalized for three days. Fatigue was the most common delayed complication, affecting 21.1% of cases, while seizures were the least common at 1.4%. Other notable complications included cough, rhinorrhea, and nausea, with significant relationships observed between age and issues like loss of smell and decreased appetite. Underlying diseases were linked to higher rates of cough and shortness of breath.<br><br>DISCUSSION: Fatigue was the most common delayed complication of COVID-19 in hospitalized children. Younger children and those with underlying health conditions were particularly vulnerable to these delayed effects.<br><br>CONCLUSION: This study underscores the need for personalized follow-up care for pediatric patients recovering from COVID-19. Comprehensive monitoring and support programs are crucial for addressing the specific complications observed in this population, thereby ensuring improved long-term outcomes.},
}
@article {pmid40754541,
year = {2025},
author = {Zaazouee, MS and Nada, EA and Al-Kafarna, M and Shaheen, A and Ramu, SK and Hafez, AH and Matar, SG and Assar, A and Elshennawy, M and Abu El-Enien, H and Redwan, HJ and Elsayed, SM and Omran, MJ and Salloum, OH and Almadhoon, H and Mamdouh, M and Wahsh, EA and Nourelden, AZ and Elshanbary, AA and Abdel-Aziz, W and Rashid, HH and Basheti, I and Ragab, KM and Masoud, AT and Abushouk, AI and , },
title = {A multinational cross-sectional study on the prevalence and predictors of long COVID across 33 countries.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {28299},
pmid = {40754541},
issn = {2045-2322},
mesh = {Humans ; Female ; *COVID-19/epidemiology/complications ; Adult ; Male ; Cross-Sectional Studies ; Prevalence ; Middle Aged ; SARS-CoV-2/isolation &amp; purification ; Risk Factors ; Quality of Life ; Young Adult ; Aged ; Adolescent ; },
abstract = {The symptoms of long COVID (LC) can be debilitating and may be associated with anxiety, social stigma, and quality of life deterioration. Identifying patients at risk of LC is important to offer follow-up care and plan population-level public health measures. The current multinational study aimed to assess the prevalence and predictors of LC in the general population. We conducted an online, multinational, cross-sectional survey between April 2022 and January 2023, targeting participants 18 years and older with a previously confirmed COVID-19 infection. We used convenience sampling to recruit participants through an online Google form. We collected demographic data, past medical history, infection details, post-COVID-19 symptoms, and quality of life. Responses were then translated into English. LC was defined as per the World Health Organization. A single-variable analysis was conducted to identify factors significantly associated with LC development. Following the removal of multicollinear variables, a generalized linear model was established to estimate the contribution of different predictors to LC occurrence. A total of 11,801 respondents from 33 countries were included in the analysis. The mean age for participants was 32.7 ± 12.8 years, with 61% being females. BMI averaged 25.2 ± 4.8 across participants, and 14.8% of them were smokers. Seventy-eight percent of participants reported receiving the COVID-19 vaccine. Respondents with PCR-confirmed COVID-19 were then categorized into those with LC (N = 2335, 19.8%) and without LC (N = 9466 individuals, 80.2%). Our model identified 25 significant predictors. The predictors of higher LC risk included ICU admission (OR 2.08; 95% CI 1.36, 3.18; P = 0.001), female sex (OR 1.8; 95% CI 1.61, 2.02; P < 0.001), fatigue during the infection (OR 1.6; 95% CI 1.43, 1.78; P < 0.001), identifying as Hispanic (OR 1.53; 95% CI 1.26, 1.85; P < 0.001), and pre-existing gastrointestinal disease (OR 1.48; 95% CI 1.22, 1.8; P < 0.001). In conclusion, we identified key LC predictors, including ICU admission, female sex, and acute fatigue as primary risk factors, while African American and Asian ethnicities and receiving even one dose of vaccination demonstrated protective effects.},
}
@article {pmid40754067,
year = {2025},
author = {Peine, C and Stoliaroff-Pepin, A and Reinacher, U and Heldt, K and Sarganas, G and Piechotta, V and Mikolajewska, A and Pilic, A and Barkowski, N and Bleve, D and Giebeler, MH and Poser, S and Searle, L and Kißner, E and Nitsche, L and Bayram, F and Siemens, W and Ziegler, A and Meerpohl, JJ and Sandmann, F and Wichmann, O and Harder, T},
title = {Effectiveness of COVID-19 vaccines against post-COVID-19 condition/long COVID: systematic review and meta-analysis.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {31},
number = {12},
pages = {1961-1971},
doi = {10.1016/j.cmi.2025.07.026},
pmid = {40754067},
issn = {1469-0691},
mesh = {Humans ; *COVID-19/prevention &amp; control/complications ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; *Vaccine Efficacy ; SARS-CoV-2/immunology ; Vaccination ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Persons infected with SARS-CoV-2 can develop long-term symptoms known as postCOVID-19 condition (PCC; symptoms ≥3 months after infection) or long COVID (LC; symptoms ≥1 month after infection). Vaccination against COVID-19 might prevent PCC/LC, but the extent of protection is unclear.<br><br>OBJECTIVES: The aim of this systematic review was to evaluate the vaccine efficacy/effectiveness (VE) of COVID-19 vaccines given prior to SARS-CoV-2 infection in preventing PCC or LC.<br><br>METHODS DATA SOURCES: Studies were identified in Embase, MEDLINE, PreView, COVID-19 L.OVE repository, and Cochrane Library up to August 1, 2024.<br><br>Randomized controlled trials and nonrandomized studies of interventions (NRSI) that investigated immunization with a COVID-19 vaccine before SARS-CoV-2 infection were eligible, irrespective of participant age and sex.<br><br>ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed using the ''Risk Of Bias In Nonrandomized Studies-of Interventions'' tool.<br><br>METHODS OF DATA SYNTHESIS: Primary outcome was PCC, secondary outcomes were LC, time until reconvalescence, limitations in everyday activity, and quality of life. Meta-analyses were primarily conducted using the random-effects model.<br><br>RESULTS: A total of 6423 records were screened, and 65 NRSI reporting adjusted estimates were included, comprising >5.7 mio.<br><br>PARTICIPANTS: VE for &#x2265;1 vaccine dose against PCC was 41.0% (95% CI 27.8%; 51.7%; 22 NRSI, certainty of evidence: low). VE after 1, 2, or 3 doses versus unvaccinated was 19.1% (-119.4%; 70.2%, 3 NRSI), 43.2% (4.5%; 66.2%; 4 NRSI), and 70.0% (30.0%; 87.0%; 1 NRSI), respectively. In <18 years old, VE against PCC was 26% for &#x2265;1 dose (-4%; 48%, 1 NRSI) and in >60 years old 41% (17%; 59%, 1 NRSI). VE after pre-Omicron-SARS-CoV-2 infection was 32.1% (-54.3%; 70.1%, 3 NRSI) and 20.9% (-10.1%; 43.3%, 2 NRSI) after Omicron infection. Sensitivity analyses indicated no influence of risk of bias and effect measure.<br><br>CONCLUSIONS: COVID-19 vaccines may be moderately effective in preventing PCC/LC. VE may increase with the number of vaccine doses administered.},
}
@article {pmid40749814,
year = {2025},
author = {Palsson, O and Simren, M and Sperber, AD and Bangdiwala, S and Hreinsson, JP and Aziz, I},
title = {The Prevalence and Burden of Disorders of Gut-Brain Interaction (DGBI) Before vs After the COVID-19 Pandemic.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2025.07.012},
pmid = {40749814},
issn = {1542-7714},
abstract = {BACKGROUND &amp; AIMS: COVID-19 infection may increase the risk of developing disorders of gut-brain interaction (DGBI). However, the extent of this effect on a population level is poorly understood. We performed a 2-country survey to address this issue.<br><br>METHODS: A population-based Internet survey with predefined demographic quotas was conducted across the United Kingdom (UK) and United States (U.S.) in 2017 (pre-pandemic; n = 4050) and repeated in 2023 (post-pandemic; n = 4002). The surveys included the Rome IV diagnostic questionnaire, and questions about nongastrointestinal somatic symptoms, anxiety and depression, quality of life, and health care utilization. The 2023 survey also included questions regarding COVID-19 infection and illness history.<br><br>RESULTS: The overall DGBI prevalence (ie, meeting diagnostic criteria for at least 1 DGBI) has significantly increased from the pre- to post- pandemic era (38.3% vs 42.6%; odds ratio [OR], 1.20; 95% confidence interval, 1.09-1.31), with similar findings independently noted in the UK and U.S. The rise in DGBI was observed within the esophageal (8.8% vs 10.1%; OR, 1.16), gastroduodenal (11.9% vs 16.4%; OR, 1.45), and bowel domains (30.1% vs 32.5%; OR, 1.12). The 2 most widely investigated DGBIs showed large post-pandemic prevalence increases, with functional dyspepsia rising from 8.3% to 11.9% (OR, 1.48) and irritable bowel syndrome from 4.7% to 6.0% (OR, 1.31). In multivariable analysis, factors significantly associated with having DGBI in the post-pandemic era included younger age, female sex, anxiety, depression, medium-to-high somatic symptom severity, increasing number of COVID-19 infections, experiencing abdominal pain or diarrhea during COVID-19 infection, and suffering with long COVID. Individuals with DGBI in the post-pandemic era, in particular those with long COVID, reported reduced quality of life and higher mood disturbances, somatic symptom reporting, and health care use than individuals with DGBI in the pre-pandemic era.<br><br>CONCLUSION: The population prevalence and burden of DGBI have increased following the COVID-19 pandemic. Health care services and research funding bodies need to adapt to this post-COVID rise in DGBI and address how to best manage this patient group.},
}
@article {pmid40748784,
year = {2026},
author = {Pollett, S and Agan, BK and Letizia, AG and Richard, SA and Porter, C and Epsi, NJ and Haigney, M and Saunders, D and Colombo, R and Burgess, TH and Morris, M and Tribble, DR and La Croix, C and Jones, M and O'Connell, RJ},
title = {Long COVID and the Military: A Current Research Landscape, Knowledge Gaps, and Future Directions.},
journal = {Military medicine},
volume = {191},
number = {1-2},
pages = {e102-e110},
doi = {10.1093/milmed/usaf343},
pmid = {40748784},
issn = {1930-613X},
support = {HU00012120103//Defense Health Program/ ; //Disease Clinical Research Program/ ; //Department of Defense/ ; //Uniformed Services University of the Health Sciences/ ; //Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc./ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Military Personnel/statistics &amp; numerical data ; Post-Acute COVID-19 Syndrome ; United States/epidemiology ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: This narrative review highlights the impact and epidemiology of post-COVID conditions (PCC, 'Long COVID') in military service members and beneficiaries, characterizing the threat of Long COVID to military readiness. We leveraged this review to propose a Long COVID research road map for Military Health System (MHS)-based studies, identifying key questions and knowledge gaps that the Department of Defense research enterprise is well-positioned to address.<br><br>MATERIALS AND METHODS: We searched MEDLINE (PubMed) in addition to MHS conference abstracts and websites, bibliographies of relevant published articles and https://clinicaltrials.gov/.<br><br>RESULTS: Multiple studies in U.S., U.K., and European military service members have noted medically attended and patient reported post-acute sequelae and symptoms across the domains of cardiorespiratory, neurocognitive, and mental health. Studies have also noted an association with SARS-CoV-2 infection and fitness in young adult service members, but the ongoing prevalence, morbidity, and functional impact of Long COVID in military populations in the current era remains unclear. All identified studies have limitations.<br><br>CONCLUSIONS: Considerable research has been conducted to understand the risk of and risk factors associated with Long COVID in active duty, much in the earlier pandemic period. Future research priorities include establishing Long COVID definitions most relevant to active duty personnel and conducting studies to delineate, treat, and prevent Long COVID's impact on cognitive, cardiorespiratory, and overall health and fitness for duty. Many considerations in this review article may also apply to post-acute sequelae from other infectious diseases, which pose risks to military health and readiness, including future respiratory virus pandemics.},
}
@article {pmid40748012,
year = {2025},
author = {Waxse, BJ and Rao, S},
title = {Data science for pediatric infectious disease: utilizing COVID-19 as a model.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {5},
pages = {493-498},
pmid = {40748012},
issn = {1473-6527},
support = {ZIA HG200417/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Child ; *Data Science/methods ; SARS-CoV-2 ; Pediatrics ; Pandemics ; Public Health ; },
abstract = {PURPOSE OF REVIEW: During the COVID-19 pandemic, governments and public health agencies used data science tools and data sources in real time to evaluate pathogen transmissibility, disease burden, healthcare capacity, and evaluate treatment and preventive measures. The purpose of the review is to highlight the application of these data sources and methods during the COVID-19 response.<br><br>RECENT FINDINGS: Advances in the development of common data models enabled multisite data networks to overcome healthcare data fragmentation, enabling national surveillance platforms, and offering unprecedented statistical power to conduct national surveillance and detect emerging clinical entities like MIS-C and long COVID in diverse pediatric populations. These integrated networks were also used in evaluating the effectiveness of vaccines and therapies. New surveillance approaches combining traditional clinical data with novel data sources including wastewater detection, web-based search engines, and mobility patterns yielded comprehensive ensemble approaches that informed public health policy.<br><br>SUMMARY: The COVID-19 pandemic highlighted the importance of timely evidence for decision-making during outbreak responses and the benefits of using data science tools to help provide real time, actionable insights, which can help guide our public health response to infectious diseases threats in the future.},
}
@article {pmid40747935,
year = {2025},
author = {Yip, A and Yip, J and Tsui, Z and Chan, CA and Lam, CP and Ching, JL and Yip, RK and Smith, GD},
title = {Weathering the Double Storm-Resilience in Chinese Older Cancer Patients With Long COVID: A Qualitative Study.},
journal = {Journal of advanced nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jan.70106},
pmid = {40747935},
issn = {1365-2648},
support = {//This research was funded by the Institutional Development Grant (IDG) from Saint Francis University (Reference no: IDGP240211)./ ; },
abstract = {AIM: To explore the lived experiences of Chinese older adult cancer patients in Hong Kong navigating the challenges of long COVID.<br><br>DESIGN: A descriptive phenomenological study.<br><br>METHODS: Semi-structured interviews were conducted with 27 purposively sampled older Chinese cancer survivors in Hong Kong between January 2023 and January 2024. Data were analysed using Colaizzi's thematic analysis method.<br><br>RESULTS: Four key themes emerged: (1) the invisible scars of COVID-19: unrecognised and diverse symptoms; (2) the double-edged sword of protection: shielding from COVID-19 while battling cancer and long COVID; (3) forging strength in the crucible: adapting and thriving with cancer and long COVID and (4) nurturing resilience: the integral role of nursing in supporting cancer patients with long COVID during a pandemic.<br><br>CONCLUSION: Older Chinese cancer patients with long COVID experience a dual burden of unrecognised physical symptoms and profound psychological distress from isolation. Despite this, they demonstrate remarkable resilience, a process that can be actively supported through specialised nursing care.<br><br>ORIGINALITY/NOVELTY: This study offers original contributions to the limited literature on the intersection of cancer, long COVID, and ageing. It provides in-depth insights into the lived experiences of this vulnerable population, highlighting the diversity of long COVID symptoms, the psychological impact of pandemic-related precautions, and the crucial role of nursing in fostering resilience.<br><br>IMPACT: This study highlights the urgent need for nurses to recognise the unique challenges of this population. It provides a foundation for developing nurse-led, resilience-focused interventions that integrate tailored education, emotional support, and resource navigation into oncology care. These findings can inform practice and policy to better support the well-being of a vulnerable and growing patient demographic.<br><br>REPORTING METHOD: The study adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist.<br><br>No patient or public contribution.},
}
@article {pmid40746934,
year = {2025},
author = {Frediani, MM and Ribeiro, HS and Busatto, GF and Carvalho, CRR and Burdmann, EA},
title = {Renal Long COVID: A Scoping Review.},
journal = {Kidney medicine},
volume = {7},
number = {8},
pages = {101039},
pmid = {40746934},
issn = {2590-0595},
abstract = {RATIONALE &amp; OBJECTIVE: Whether long coronavirus disease (long COVID) affects the kidneys remains to be understood. In this scoping review, we described the evidence of renal long COVID.<br><br>STUDY DESIGN: A scoping review was conducted according to the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines by searching MEDLINE, Embase, and other databases from inception until February 2025.<br><br>We included evidence on kidney-related outcomes in adult survivors of coronavirus disease 2019 (COVID-19) with data on long COVID.<br><br>Cohorts from all settings.<br><br>DATA EXTRACTION: We extracted data related to longitudinal kidney outcomes.<br><br>ANALYTICAL APPROACH: Data were synthesized and presented in tables and figures.<br><br>RESULTS: We screened 6,203 studies and included 37 in this review (38 reports), comprising 1,308,265 individuals with follow-up data. The majority were retrospective (61%) and from Europe (37%). All reports included hospitalized patients and 34% also included the community setting. Acute kidney injury (AKI) during acute COVID-19 phase was assessed in 58% of the reports. Chronic kidney disease (CKD) development was assessed in 29% of the reports, with wide variation in its frequency, ranging from 0.4%-45%. Progression of CKD (7 studies, 18%) ranged from 8%-49%. Studies reporting higher frequencies of AKI found larger rates of renal long COVID. Overall, there was high heterogeneity in how kidney-related outcomes were reported during follow-up. Most studies presented data on crude kidney function biomarkers (eg, serum creatinine or estimated glomerular filtration rate), while a few (13%) reported major adverse kidney events. Data on proteinuria or urinary biomarkers were scarce.<br><br>LIMITATIONS: Lack of studies with pre-COVID-19 data.<br><br>CONCLUSIONS: This scoping review highlighted that renal long COVID, characterized by CKD development and/or progression, may occur. Available evidence suggests that AKI may be associated with renal long COVID. Therefore, long-term kidney function monitoring is advisable after COVID-19 recovery to enable early diagnosis and timely intervention for CKD.},
}
@article {pmid40746715,
year = {2025},
author = {Shani, M and Wübbelt, K},
title = {Coping with long-COVID stigma: The role of self-compassion and self-coldness.},
journal = {Health psychology open},
volume = {12},
number = {},
pages = {20551029251349409},
pmid = {40746715},
issn = {2055-1029},
abstract = {Long COVID has been associated with stigmatization, prompting exploration of coping mechanisms. This cross-sectional study examined whether self-compassion and self-coldness mediate long-COVID stigma's effects on well-being. We surveyed 201 German adults with long-COVID (89% female; M age = 43.27, SD = 10.57). Most were officially diagnosed (88%), and 93% still experienced long-COVID symptoms at the time of survey. Measures included stigma, self-compassion, self-coldness, subjective well-being (SWB), and flourishing. Long-COVID stigma negatively correlated with SWB and flourishing. Higher self-compassion and lower self-coldness predicted better outcomes. Internalized stigma predicted lower flourishing through decreased self-compassion and increased self-coldness. In contrast, enacted stigma was associated with higher SWB and flourishing through lower self-coldness. Overall, mediation effects via self-coldness were significantly stronger than those via self-compassion, particularly in flourishing. These findings highlight the interplay between stigma, self-relating, and well-being, indicating both adaptive and maladaptive pathways. Interventions promoting self-compassion and reducing self-coldness may support holistic long-COVID care.},
}
@article {pmid40744539,
year = {2025},
author = {Zhou, W and Larson, JL and Veliz, PT and Kitto, K and Smith, S},
title = {Profiles of long COVID symptoms and self-efficacy for self-management: A cross-sectional survey.},
journal = {Applied nursing research : ANR},
volume = {84},
number = {},
pages = {151968},
doi = {10.1016/j.apnr.2025.151968},
pmid = {40744539},
issn = {1532-8201},
mesh = {Humans ; *COVID-19/complications/psychology/therapy ; Cross-Sectional Studies ; *Self Efficacy ; Female ; Male ; Adult ; *Self-Management/psychology ; Middle Aged ; Surveys and Questionnaires ; Aged ; SARS-CoV-2 ; *Self Care ; },
abstract = {BACKGROUND: Some patients with COVID-19 experience prolonged symptoms, known as long COVID. Self-management promises to improve symptoms, but little is known about the role of self-efficacy for long COVID symptom management.<br><br>OBJECTIVES: To identify distinct subgroups of patients experiencing long-term post-COVID symptom burden, and to examine the association between the identified subgroups and self-efficacy for symptom management.<br><br>METHODS: A cross-sectional survey design with a convenience sampling approach. This study included 491 adults who reported experiencing long COVID symptoms. Symptoms (fatigue, dyspnea, sleep disturbance, anxiety), and self-efficacy for self-management (Self-Efficacy for Managing Chronic Disease (SEMCD) and PROMIS Self-Efficacy) were collected. Latent Profile Analysis (LPA) was used to identify profiles of adults with similar patterns of long COVID symptoms. Multinomial logistic regression was used to examine the association between self-efficacy for self-management and distinct profiles, controlling for socio-demographics and health-related characteristics. Participants' strategies to relieve COVID symptoms were collected via open-ended questions and analyzed using content analysis.<br><br>RESULTS: The mean age was 40.6 (SD&#xa0;=&#xa0;14.1) years of age. We identified four profiles based on the long COVID symptom burden: "low burden," "medium burden with low depression," "medium burden with high depression," and "high burden." Participants with a higher score of SEMCD were less likely to be in Group 3 (medium burden with high depression) (RRR: 0.76, 95&#xa0;% CI: 0.60-0.96, P&#xa0;=&#xa0;0.024) and Group 4 (high burden) (RRR: 0.71, 95&#xa0;% CI: 0.50-1.00, P&#xa0;=&#xa0;0.049). Participants with a higher score on PROMIS Self-Efficacy were less likely to be in Group 3 (RRR&#xa0;=&#xa0;0.95, 95&#xa0;% CI: 0.90-1.00, P&#xa0;=&#xa0;0.047). Participants used a range of wellness activities and self-medication strategies to self-manage symptoms.<br><br>CONCLUSION: Patients with long COVID had four distinct symptom profiles. Greater self-efficacy was associated with the profiles of less symptom burden. Self-efficacy for self-management could be an important target to consider when developing interventions to improve symptom self-management and reduce long COVID symptom burden.},
}
@article {pmid40744071,
year = {2025},
author = {Mughal, S and Andújar-Sánchez, F and Sabater-Arcis, M and Garrabou, G and Fernández-Solà, J and Alegre-Martin, J and Sanmartin-Sentañes, R and Castro-Marrero, J and Esteve-Codina, A and Casals, E and Fernández-Costa, JM and Ramón-Azcón, J},
title = {Metabolic adaptation and fragility in healthy 3Din vitroskeletal muscle tissues exposed to chronic fatigue syndrome and Long COVID-19 sera.},
journal = {Biofabrication},
volume = {17},
number = {4},
pages = {},
doi = {10.1088/1758-5090/adf66c},
pmid = {40744071},
issn = {1758-5090},
mesh = {*Fatigue Syndrome, Chronic/metabolism/blood/pathology/physiopathology ; Humans ; *COVID-19/blood/metabolism ; *Muscle, Skeletal/metabolism/pathology ; SARS-CoV-2 ; *Adaptation, Physiological ; Mitochondria/metabolism ; Male ; Muscle Contraction ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long Covid-19 (LC-19) are complex conditions with no diagnostic markers or consensus on disease progression. Despite extensive research, noin vitromodel exists to study skeletal muscle wasting, peripheral weakness, or potential therapies. We developed 3Din vitroskeletal muscle tissues to map muscle adaptations to patient sera over time. Short exposures (48 H) to patient sera led to a significant reduction in muscle contractile strength. Transcriptomic analysis revealed the upregulation of protein translation, glycolytic enzymes, disturbances in calcium homeostasis, hypertrophy, and mitochondrial hyperfusion. Structural analyses confirmed myotube hypertrophy and elevated mitochondrial oxygen consumption In ME/CFS. While muscles initially adapted by increasing glycolysis, prolonged exposure (96-144 H) caused muscle fragility and weakness, with mitochondria fragmenting into a toroidal conformation. We propose that skeletal muscle tissue in ME/CFS and LC-19 progresses through a hypermetabolic state, leading to severe muscular and mitochondrial deterioration. This is the first study to suggest such transient metabolic adaptation.},
}
@article {pmid40744021,
year = {2025},
author = {Komaroff, AL and Dantzer, R},
title = {Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Cell reports. Medicine},
volume = {6},
number = {8},
pages = {102259},
pmid = {40744021},
issn = {2666-3791},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; R21 NS130712/NS/NINDS NIH HHS/United States ; R01 CA193522/CA/NCI NIH HHS/United States ; U54 AI138370/AI/NIAID NIH HHS/United States ; R01 NS073939/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/pathology/etiology/physiopathology ; *COVID-19/complications/pathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Microbiome ; },
abstract = {Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation. Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.},
}
@article {pmid40740638,
year = {2025},
author = {Verduci, E and Risè, P and Fiore, G and Vizzuso, S and Bonomi, A and Dilillo, D and Fiori, L and Di Profio, E and Calcaterra, V and Mannarino, S and Zoia, E and D'Auria, E and Sala, A and Zuccotti, G},
title = {Exploratory study of the effect of DHA supplementation on blood fatty acids and inflammatory markers in children with MIS-C.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1597868},
pmid = {40740638},
issn = {2296-861X},
abstract = {BACKGROUND AND AIMS: Children infected with SARS-CoV-2 may develop multisystem inflammatory syndrome (MIS-C) 4-6 weeks after exposure. MIS-C is characterized by elevated markers of inflammation and low blood values of linoleic acid (LA), arachidonic acid (AA) and docosahexaenoic acid (DHA) during acute phase. The aim of this pilot exploratory study was to assess the short-term beneficial impact on the blood fatty acid profile following DHA supplementation in children who have suffered from MIS-C.<br><br>METHODS: Fifty-two children aged 2-18&#x202f;years with diagnosed MIS-C, were enrolled between December '20 and March '22. Blood samples were collected at hospital discharge (T0), and at 3 (T1) and 6&#x202f;months (T2) post-discharge using dried blood spots for fatty acid analysis by gas chromatography. Inflammatory and metabolic blood markers were assessed at T0 and T2. All participants received healthy dietary advice throughout the study. In Group 1 23 consecutive patients received DHA supplementation (250&#x202f;mg/day of DHA) from T0 to T1, followed by dietary advice alone until T2. In Group 2 29 children with MIS-C received only dietary advice throughout the observation period.<br><br>RESULTS: An altered inflammatory status, independent of treatment, was shown in all children compared to pediatric reference values. After intervention, Group 1 experienced a significant enrichment in both total n-6 and n-3 blood FAs when compared to baseline (p&#x202f;<&#x202f;0.0001). Specifically, there was a significant increase of DHA (1.19&#x202f;&#xb1;&#x202f;0.25 at T0 vs. 2.67&#x202f;&#xb1;&#x202f;0.78 at T1) and EPA (0.32&#x202f;&#xb1;&#x202f;0.09 at T0 vs. 0.46&#x202f;&#xb1;&#x202f;0.10 at T1) levels, that remained consistent at T2 (p&#x202f;=&#x202f;0.0002 and p&#x202f;<&#x202f;0.0001, respectively). Within Group 2 only n-3 alpha linolenic acid (ALA) significantly increased at T1 compared to baseline (p&#x202f;<&#x202f;0.05). The total increase in n-3 after intervention (&#x394;T1-T0) was significantly higher in Group 1 compared to Group 2 [1.90(0.9) vs. 0.49(0.8), p&#x202f;<&#x202f;0.0001 and p adj&#x202f;=&#x202f;0.005]. Erythrocyte sedimentation rate (ESR) and IL-6 showed a better tendency toward normalization in Group 1, although without statistical significance.<br><br>CONCLUSION: This pilot study is the first to explore the potential effects of DHA supplementation in children with MIS-C. DHA was associated with improvements in the blood fatty acid profile, which persisted beyond the supplementation period, and showed a trend toward normalization of selected biochemical parameters. Further adequately powered, controlled studies are needed to confirm these observations and to evaluate the potential role of early n-3 PUFA supplementation during the stable and recovery phases in critically ill pediatric patients.},
}
@article {pmid40738888,
year = {2025},
author = {Alcalde-Herraiz, M and Iqbal, S and Wallin, JJ and Liu, Y and Nieves, W and Berry, M and Catala, M and Prieto-Alhambra, D and Xie, J},
title = {Sociodemographic factors, biomarkers and comorbidities associated with post-acute COVID-19 sequelae in UK Biobank.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {7009},
pmid = {40738888},
issn = {2041-1723},
support = {SRF-2018-11-ST2-004).//DH | NIHR | Health Services and Delivery Research Programme (HS&amp;DR Programme)/ ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/blood ; Male ; Female ; United Kingdom/epidemiology ; Middle Aged ; Biomarkers/blood ; Biological Specimen Banks ; Comorbidity ; Case-Control Studies ; Aged ; SARS-CoV-2/isolation &amp; purification ; Adult ; Post-Acute COVID-19 Syndrome ; Sociodemographic Factors ; Risk Factors ; UK Biobank ; },
abstract = {Long-term sequelae of COVID-19 remain critical public health concerns, with limited therapeutic options available. We conducted two case-control studies among COVID-19 infected individuals in the UK Biobank to explore the association of sociodemographic factors, clinical biomarkers, and comorbidities with the risk of two key phenotypes: Long COVID (LC, defined by patient self-report symptoms) and post-acute complications of SARS-CoV-2 infection (PACS, defined by clinical diagnosis), separately. Our study included 8,668 participants in the LC cohort (32% classified as cases) and 108,407 in the PACS cohort (with 2% being cases). Findings showed that age and sex were associated with both LC and PACS but in opposite directions. Additionally, obesity, socioeconomic deprivation, elevated C-reactive protein, triglyceride, vitamin D, HbA1c, cystatin C, urate, and alanine aminotransferase, and decreased HDL cholesterol and IGF-1, as well as CKD and COPD, were associated with LC. Most of these factors were also significant for PACS, except for alanine aminotransferase and vitamin D. These findings have potential mechanistic implications for the distinction between LC and PACS and can guide clinical implementation of identifying high-risk groups for targeted vaccination or other public health mitigation strategies.},
}
@article {pmid40738768,
year = {2025},
author = {Lemogne, C and Verduzco-Gutierrez, M and Burton, C},
title = {Integrative approaches to the understanding and treatment of long COVID syndrome.},
journal = {Journal of psychosomatic research},
volume = {196},
number = {},
pages = {112334},
doi = {10.1016/j.jpsychores.2025.112334},
pmid = {40738768},
issn = {1879-1360},
}
@article {pmid40738266,
year = {2025},
author = {Rubin, LH and Shi, W and Azola, A and Bhattacharyya, A and Dastgheyb, RM and Wu, J and Penna, CD and Parker, H and Santiuste, I and Ehrenspeck, A and Coughlin, JM and Vannorsdall, TD and Lu, H and Veenhuis, R},
title = {Blood-Brain barrier disruption in long COVID and cognitive correlates: A cross-sectional MRI study.},
journal = {Brain, behavior, and immunity},
volume = {129},
number = {},
pages = {989-999},
pmid = {40738266},
issn = {1090-2139},
support = {P41 EB031771/EB/NIBIB NIH HHS/United States ; R01 AG064792/AG/NIA NIH HHS/United States ; RF1 MH133411/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; *Blood-Brain Barrier/diagnostic imaging/physiopathology/metabolism ; *COVID-19/physiopathology/complications/diagnostic imaging/psychology/metabolism ; Female ; Male ; Magnetic Resonance Imaging/methods ; Middle Aged ; Adult ; Cross-Sectional Studies ; *Cognition/physiology ; SARS-CoV-2 ; Brain/diagnostic imaging ; Aged ; Cognitive Dysfunction/physiopathology/diagnostic imaging ; },
abstract = {Disruption of the blood-brain barrier (BBB) may contribute to neuropsychiatric symptoms observed in Long COVID (LC). Using a non-contrast magnetic resonance imaging (MRI) technique, we investigated BBB permeability in individuals with LC and its relationship to cognitive function. We hypothesized that LC individuals would show greater BBB permeability than recovered individuals, and that higher permeability would correlate with poorer cognition. Ninety-seven participants meeting the 2024 NASEM definition of LC with at least one neuropsychiatric symptom and 31 recovered controls completed an MRI scan and cognitive testing. BBB permeability was assessed using water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) MRI, which estimates the permeability-surface-area product (PS) of arterially labeled water entering the brain. Cognitive performance was summarized into eight factor scores derived from principal components analysis. Compared to controls, the LC group was older (M = 47 vs. 39 years, P = 0.003), less educated (P = 0.02), more likely female (P = 0.04), and had higher hospitalization rates for COVID-19 (P = 0.02). PS was significantly elevated in the LC group after adjusting for age and sex (B = 18.59, SE = 6.11, β = 0.28, P = 0.003). No significant group differences were found in cerebral blood flow, extraction fraction (E), or brain volume. Within the LC group, higher PS was associated with poorer motor function, but not with other cognitive domains. These findings indicate subtle but persistent BBB disruption in LC individuals over two years post-infection, with a potential link to motor dysfunction. This supports prior evidence of BBB changes following severe COVID-19 and suggests that BBB integrity may be a long-term biomarker of neuropsychiatric complications in LC.},
}
@article {pmid40738238,
year = {2025},
author = {Maison, DP and Khadka, VS and Mohd-Ibrahim, I and Peluso, MJ and Henrich, TJ and Deng, Y and Gerschenson, M},
title = {Peripheral immune progression to long COVID is associated with mitochondrial gene transcription: A meta-analysis.},
journal = {Mitochondrion},
volume = {85},
number = {},
pages = {102072},
pmid = {40738238},
issn = {1872-8278},
support = {P20 GM103466/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; U54 HG013243/HG/NHGRI NIH HHS/United States ; U54 GM138062/GM/NIGMS NIH HHS/United States ; P20 GM113134/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/immunology/genetics ; Disease Progression ; *Genes, Mitochondrial ; Leukocytes, Mononuclear/immunology ; *Mitochondria/genetics ; *Transcription, Genetic ; *Post-Acute COVID-19 Syndrome/genetics/immunology ; },
abstract = {SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has led to millions of cases of Long COVID worldwide. Long COVID is a phenomenon characterized by persistent and debilitating mental and physical symptoms following acute infection. Despite ongoing research, trials, and considerable progress in understanding Long COVID, its exact causes remain only partially understood, with current hypotheses addressing specific aspects of the condition. We conducted one of the most comprehensive meta-analyses to date of all quality bulk RNA-seq studies worldwide from the COVID-19 pandemic and show significant mitochondrial transcript changes in the peripheral immune system of people with Long COVID, with unexpectedly low levels of intracellular viral RNA in Long COVID. This extensive analysis, which includes 26 studies and 1,272 individuals, shows that mononuclear cells, PBMC, and granulocytes from Long COVID patients exhibit significant alterations in mitochondrial genes and related processes. These findings likely represent the true transcriptomic landscape of Long COVID across diverse datasets, highlighting the long-lasting impacts of SARS-CoV-2 on peripheral immune function. In combination with other ex vivo and proteomics studies showing mitochondrial dysfunction, our results suggest critical new directions, such as the potential role of clonal hematopoiesis and infected seed cells. This work highlights the need for further investigation into the mechanisms underlying these immune changes and persistent symptoms in people with Long COVID. These findings will serve as a foundation for defining the paradigm underlying the biological mechanisms of Long COVID, driving research into the peripheral immune system, bone marrow, and mitochondria.},
}
@article {pmid40737552,
year = {2026},
author = {Kaur, U and Chakrabarti, SS},
title = {COVID-19 vaccine safety studies- the need for a third group for extended monitoring.},
journal = {Expert opinion on drug safety},
volume = {25},
number = {1},
pages = {1-7},
doi = {10.1080/14740338.2025.2542249},
pmid = {40737552},
issn = {1744-764X},
mesh = {Humans ; *COVID-19/prevention &amp; control/immunology ; *COVID-19 Vaccines/adverse effects/administration &amp; dosage ; Time Factors ; Vaccination/adverse effects/methods ; Vaccine Efficacy ; },
abstract = {INTRODUCTION: Studies assessing COVID-19 vaccine effectiveness have generally categorized individuals into 'vaccinated' and 'unvaccinated' groups. Long-term safety studies are sparse and have usually compared adverse events with background rates. Studies on timing of COVID-19 vaccination as a determinant of long COVID have provided variable results, while there is scarce data on timing of vaccination as a determinant of adverse events.<br><br>AREAS COVERED: We discuss some of our observations as well as the global evidence on the timing of COVID-19 vaccination as a determinant of long-COVID and adverse events. This special report is hypothesis-generating and aims to propose a conceptual framework and not establish causality.<br><br>EXPERT OPINION: We propose an alternative classification strategy for COVID-19 vaccinees, with special emphasis on individuals who received any dose of vaccination after recovering from natural COVID-19, i.e. the 'vaccine-after-COVID' (VAC) group. These individuals should be followed up for an extended period through multicentric and database studies. This may help in understanding the long-term safety of COVID-19 vaccines and the natural course of long COVID. Immunological characteristics of this group should also be scrutinized. The evidence gained might be useful in planning vaccination policies in the event of future pandemics.},
}
@article {pmid40736492,
year = {2025},
author = {Grad, R and Ebell, MH},
title = {Top 20 Research Studies of 2024 for Primary Care Physicians.},
journal = {American family physician},
volume = {112},
number = {1},
pages = {34-41},
pmid = {40736492},
issn = {1532-0650},
mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; *Physicians, Primary Care ; COVID-19 ; *Primary Health Care ; SARS-CoV-2 ; },
abstract = {This article summarizes the top 20 research studies of 2024 identified as POEMs (patient-oriented evidence that matters). Based on a network meta-analysis, the oral antibiotics most likely to be effective for community-acquired pneumonia are telithromycin (not available in the United States), azithromycin, amoxicillin-clavulanate, and the quinolones levofloxacin and nemonoxacin (not available in the United States). The oral antivirals molnupiravir and nirmatrelvir-ritonavir reduce hospitalizations in immunocompromised patients with COVID-19. In average-risk infants, a single dose of nirsevimab reduces hospitalizations due to respiratory syncytial virus. Amoxicillin with or without clavulanate is more effective than placebo for children with symptoms of acute sinusitis. Benzyl benzoate 25% is highly effective for scabies in adolescents and adults. Lactobacillus-containing probiotics reduce the incidence of recurrent urinary tract infections (UTIs) in premenopausal women with frequent UTIs. Low-dose amitriptyline is effective as second-line therapy for irritable bowel syndrome. For patients with uncomplicated gallstones, conservative management is a reasonable option. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are better than older drugs at improving patient-oriented outcomes for type 2 diabetes. Continuous or intermittent glucose monitoring is minimally effective for control of type 2 diabetes and can be harmful. Phentermine-topiramate and GLP-1 receptor agonists are the most effective drugs for promoting weight loss. Semaglutide is effective for secondary prevention of cardiovascular disease in people with obesity and no diabetes. SGLT-2 inhibitors and GLP-1 receptor agonists decrease cardiovascular death in older adults with type 2 diabetes and heart failure. Beta blockers do not prevent subsequent events after myocardial infarction in patients with preserved ejection fraction. For patients who do not quit smoking after a trial of varenicline or combined nicotine replacement therapy, a higher dose of either drug can increase quit rates. e-Cigarettes increase abstinence from smoking, but long-term vaping is a consequence for some. Oral naltrexone and acamprosate are safe and effective treatments for alcohol use disorder. Cognitive behavior therapy can reduce fatigue attributed to long COVID. New monoclonal antibodies for Alzheimer disease are harmful, expensive, and minimally effective. Clinicians may choose to deliver bad news in person or by telephone, using their judgment or patient preference to decide which is best for the patient.},
}
@article {pmid40735347,
year = {2025},
author = {Hohberger, B and Ganslmayer, M and Harrer, T and Kruse, F and Maas, S and Borst, T and Heimke-Brinck, R and Stog, A and Knauer, T and Rühl, E and Zeisberg, V and Skornia, A and Bartsch, A and Ströbel, A and Wytopil, M and Merkel, C and Hofmann, S and Schmidt, KG and Lakatos, P and Schottenhamml, J and Herrmann, M and Mardin, C and Rech, J},
title = {Safety, tolerability and clinical effects of rovunaptabin, also known as BC007 on fatigue and quality of life in patients with Post-COVID syndrome (reCOVer): a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical trial (RCT).},
journal = {EClinicalMedicine},
volume = {86},
number = {},
pages = {103358},
pmid = {40735347},
issn = {2589-5370},
abstract = {BACKGROUND: Rovunaptabin neutralises functional autoantibodies targeting G-Protein coupled receptors (GPCR-fAAbs), observed in patients with Post-COVID syndrome. As we hypothesise an improvement of PCS by rovunaptabin, the aim of reCOVer was to investigate safety, tolerability, and clinical effects of rovunaptabin in PCS patients.<br><br>METHODS: reCOVer is a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical investigator initiated trial with 1350 mg rovunaptabin with additional cross-over at the Universit&#xe4;tsklinikum Erlangen, Germany. The trial was registered in EudraCT, 2022-001781-35. Screening was done between 21&#xb7;11&#xb7;2023 and 25&#xb7;06&#xb7;2024. Eligible participants (18-80 years) showed GPCR-fAAbs, at least 3/8 defined PCS symptoms persisting &#x2265;3 months after COVID-19 and fatigue as major symptom. Participants were randomly assigned (1:1) to either receive rovunaptabin or placebo at day 0 (d0) and d48 with a follow-up of 28 days, respectively. Primary endpoint was the number of treatment emergent adverse events (TEAE) at d28 (co-primary endpoint: TEAE at d70); secondary endpoint focused on fatigue and quality of life.<br><br>FINDINGS: Thirty PCS patients were randomised and analysed. RCT analysis showed nine (rovunaptabin) and five TEAEs (placebo), yet without statistically significance (p = 0&#xb7;1299; CI -14&#xb7;80%; 63&#xb7;02%); one serious adverse event, not related to treatment, was recorded. Rovunaptabin showed a neutralisation of GPCR-fAAb and a significant improvement of FACIT Fatigue Scale (effect size = 2&#xb7;10, p = 0&#xb7;0378), Bell score (effect size = 3&#xb7;64, p = 0&#xb7;0004), Fatigue Severity Scale (effect size = -2&#xb7;66, p = 0&#xb7;0088), and quality of life (4/8 items).<br><br>INTERPRETATION: As this proof-of-concept study showed effects on the patient-centred endpoint PCS and a good safety profil, subsequent studies are needed to confirm these results in a larger cohort.<br><br>FUNDING: German Federal Ministry of Education and Research, German Research Foundation.},
}
@article {pmid40734821,
year = {2025},
author = {Sandoval, A and Li, M and Jason, LA},
title = {Two neurocognitive domains identified for patients with myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of COVID-19.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1612548},
pmid = {40734821},
issn = {1664-2295},
abstract = {Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Acute Sequelae of COVID-19 (PASC) often have neurocognitive complaints that involve memory and concentration problems and difficulties paying attention. Other neurocognitive domains such as hypersensitivity to noise and light have rarely been included as aspects of neurocognitive impairment for these post-viral conditions. The current study evaluated a more extensive list of neurocognitive items for a group of 2,313 patients with ME/CFS and 299 patients with PASC. Exploratory factor analyses found two factors for each patient group, one involving classic memory and concentration symptoms and the other involving sensory overload phenomena. The findings suggest that researchers might consider expanding the types of self-report neurocognitive symptoms among patients with these post-viral illnesses.},
}
@article {pmid40734755,
year = {2025},
author = {Hupin, D and Pichot, V and Bäck, M and Nygren-Bonnier, M and Reistam, U and Runold, M and Bruchfeld, J and Dupré, C and Da Costa, A and Romeyer, C and Roche, F and Ståhlberg, M and Fedorowski, A and Nickander, J},
title = {Screening for postural orthostatic tachycardia syndrome using 24-hour electrocardiogram recording in patients with long coronavirus disease.},
journal = {Heart rhythm O2},
volume = {6},
number = {7},
pages = {949-955},
pmid = {40734755},
issn = {2666-5018},
abstract = {BACKGROUND: Cardiovascular autonomic dysfunction is a major complication in a large proportion of patients with long coronavirus disease (LC). As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection.<br><br>OBJECTIVE: This study aimed to develop and test a 24-hour electrocardiogram (ECG) recording to direct the clinical suspicion toward the diagnosis of POTS.<br><br>METHODS: Consecutive patients referred to the Karolinska University Hospital in Stockholm from April 2021 to April 2022 were included. Patients with POTS were compared with patients with LC without POTS (verified by active standing tests) and control healthy subjects according to 3 specific analyses based on 24-hour ECG recording: (1) heart rate (HR) spikes of > 30 beats per minute, (2) awakening HR increase, and (3) HR variability (root mean square of successive difference). The control group consisted of healthy subjects from the database of the University Hospital of Saint-Etienne.<br><br>RESULTS: A total of 100 patients with LC (mean age, 42.54 &#xb1; 10.45 years; 92% women) and 100 healthy subjects (41.40 &#xb1; 7.21 years; 96% women) were included. LC POTS (n = 45) was associated with (1) a higher number of HR spikes/h (1.47 &#xb1; 0.84 vs 0.68 &#xb1; 0.50 and 0.40 &#xb1; 0.28/h; P < .01), (2) an abrupt and sustained increase in HR after awakening (P < .05), and (3) a reduction of HR variability: mean root mean square of successive difference of 34.90 &#xb1; 12.48 vs 30.47 &#xb1; 19.15 and 43.35 &#xb1; 21.10 ms (P < .01) compared with patients with LC without POTS (n = 55) and healthy subjects.<br><br>CONCLUSION: A triple analysis of 24-hour ECG recordings could reveal a characteristic POTS signature in LC. More research in other populations is needed to draw any firm conclusions about its generalizability.},
}
@article {pmid40733521,
year = {2025},
author = {Mahajan, S and Mahajan, S and Patgiri, S},
title = {Association and Interaction of Epstein-Barr Virus with SARS-CoV-2 Infection-A Review.},
journal = {Viruses},
volume = {17},
number = {7},
pages = {},
pmid = {40733521},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/virology/complications/immunology ; *Herpesvirus 4, Human/physiology ; *Epstein-Barr Virus Infections/virology/complications/drug therapy ; *SARS-CoV-2/physiology ; Virus Activation ; },
abstract = {Despite the significant decrease in SARS-CoV-2-related mortality, COVID-19 continues to impose a high public health burden due to the high rate of post-COVID-19 pathological conditions, broadly termed Long COVID, that continue for any period of time and are generally multisystemic. However, recent studies have strengthened the evidence that the reactivation of the Epstein-Barr virus (EBV) in the post-COVID-19 era has significantly contributed to the exacerbation and prolongation of Long COVID symptoms. The mechanism and pathophysiology of EBV reactivation in Long COVID patients still need further exploration due to limited studies. This review summarises the various studies linking EBV reactivation in Long COVID along with its pathophysiology and novel therapeutics for EBV in a post-COVID-19 era.},
}
@article {pmid40730806,
year = {2025},
author = {Bunker, T and Horne, BD and Baldwin, MD and Sorrells, R and Turner, S and Laube, L and Solomon, A and Horne, LA and Novack, J},
title = {Intermittent fasting and a no-sugar diet for Long COVID symptoms: a randomized crossover trial.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27563},
pmid = {40730806},
issn = {2045-2322},
mesh = {Humans ; *Fasting ; Male ; Female ; *COVID-19/diet therapy ; Cross-Over Studies ; Middle Aged ; Adult ; SARS-CoV-2 ; Aged ; Treatment Outcome ; Intermittent Fasting ; },
abstract = {Long COVID (LC) is a common chronic health condition that impairs daily functioning and social connections. This is the first randomized clinical trial to directly compare the effect of two Intermittent Fasting regimens on LC symptoms. The main objectives of this 10-week randomized cross-over trial are to compare the efficacy and safety of 4 weeks of 1-2 day fasting plus a restricted diet vs 4 weeks of mild time-restricted eating (TRE) and a restricted diet in reducing patient-reported LC symptoms. After a 2-week run-in, subjects were randomized to treatment A (TRE) or treatment B (Fasting) for 4 weeks. Subjects then crossed over to the other treatment for 4 weeks. The median fasting duration was 38 h (night-day-night), and the mean duration was 42 h. Symptoms were assessed via weekly online surveys. Primary outcomes were changes in LC symptom severity scores (LC-Scores) and in the number of LC symptoms (numLCsym) between treatments. Secondary outcomes were changes in LC-Scores and numLCsym over the 10-week trial. Fasting was superior to TRE alone in reducing LC-Scores (p = 0.008). The numLCsym decreased - 5.0 during the Fasting 4 weeks vs - 1.4 in the TRE 4 weeks (p = 0.002). Altogether, the 10-week regimen of a no-sugar diet, TRE and Fasting decreased the mean LC-Score by 51.8% (p < 0.0001) from 37.8 to 18.2. Similarly, numLCsym decreased from 20.5 to 12.2, a decrease of 40.6% (p < 0.0001). No major adverse safety events were recorded. Both intermittent fasting interventions decreased symptoms over the 10-week trial but the more intense fasting regimen was significantly better.Trial registration: ClinicalTrials.gov Identifier NCT06214455.},
}
@article {pmid40729248,
year = {2025},
author = {Carpallo-Porcar, B and Beamonte, EDC and Jiménez-Sánchez, C and Córdova-Alegre, P and Brandín-de la Cruz, N and Calvo, S},
title = {Multimodal Telerehabilitation in Post COVID-19 Condition Recovery: A Series of 12 Cases.},
journal = {Reports (MDPI)},
volume = {8},
number = {1},
pages = {},
pmid = {40729248},
issn = {2571-841X},
abstract = {Background: Post COVID-19 Condition is a recently recognized syndrome characterized by the persistence of various symptoms, including dyspnea, physical and mental fatigue, and post-exertional malaise. Currently, there is no established treatment or clear consensus on the effectiveness of rehabilitation, and given that patients could benefit from home-based rehabilitation, telerehabilitation, defined as remote rehabilitation using telematic systems, may be an option to reach more of the population with persistent COVID-19 symptoms. Therefore, it is necessary to show the efficacy of this telematic approach and the benefits of a multimodal rehabilitation strategy in these patients. Methods: Patients underwent home rehabilitation using a 12-week synchronous telerehabilitation system. The intervention included therapeutic education and physical and respiratory rehabilitation. The following variables were analyzed: Fatigue, quality of life, dyspnea, respiratory strength, aerobic capacity, and upper and lower limb strength. Conclusions: After 12 weeks, significant improvements were found in fatigue, aerobic capacity, and limb and respiratory strength. However, no improvement was found in dyspnea scores, which did not correlate with respiratory strength. Interestingly, a post-intervention correlation emerged between the distance covered in aerobic capacity and perceived fatigue, suggesting that asynchronous telerehabilitation could be a viable treatment strategy for these patients.},
}
@article {pmid40728641,
year = {2025},
author = {Daungsupawong, H and Wiwanitkit, V},
title = {Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue: a comment.},
journal = {Wiener klinische Wochenschrift},
volume = {137},
number = {19-20},
pages = {642-643},
pmid = {40728641},
issn = {1613-7671},
}
@article {pmid40728640,
year = {2025},
author = {Crevenna, R and Keilani, M},
title = {Authors' response to the letter to the editor "Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue".},
journal = {Wiener klinische Wochenschrift},
volume = {137},
number = {19-20},
pages = {644},
pmid = {40728640},
issn = {1613-7671},
}
@article {pmid40727350,
year = {2025},
author = {Yao, Y and Liu, S and Zhang, Y and Liu, C and Shi, J and Chen, B and Yang, Z and Zhang, T and Li, Z and Gao, S},
title = {Case study of a 47-year-old long COVID patient diagnosed with Alzheimer's disease.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {7},
pages = {6535-6540},
pmid = {40727350},
issn = {2223-4292},
}
@article {pmid40726775,
year = {2025},
author = {Giménez-Orenga, K and Pierquin, J and Brunel, J and Charvet, B and Martín-Martínez, E and Lemarinier, M and Fried, S and Lucas, A and Perron, H and Oltra, E},
title = {Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {48},
number = {},
pages = {101058},
pmid = {40726775},
issn = {2666-3546},
abstract = {Post-COVID-19 condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), are characterized by fatigue, pain, shortness of breath, sleep disturbances, cognitive dysfunction and other symptoms, heavily impacting on patients daily functioning. Moreover, over half of patients end up fulfilling ME/CFS and/or FM clinical criteria after a few months of SARS-CoV-2 infection. Expression of the toxic human endogenous retrovirus (HERV)-W ENV protein can be induced by viral infection and HERV-W detection was correlated with acute COVID-19 severity and found significantly expressed in post-COVID-19 condition. This study shows that HERV-W ENV may also be present in prepandemic cases of ME/CFS, FM or co-diagnosed with both clinical criteria, suggesting viral participation in these chronic diseases. To learn whether associated antiviral mechanisms may also show differing patterns of immunological responses, we measured IgM, IgG, IgA and IgE antibody isotypes against SARS-CoV-2 spike and nucleocapsid antigens, the levels of IL-6, IL-8, IL-10, IFNγ and TNFα cytokines, the level of NfL, a neural damage biomarker, as well as some blood cell markers potentially related with fatigue. Importantly, some of the measured variables showed a capacity to discriminate post-COVID-19 condition cases from all other participants, with 100 % sensitivity and up to 71.9 % specificity providing a new tool for a differential diagnosis between diseases or syndromes with so many overlapping clinical symptoms. Interestingly, the detected markers showed moderate-to-strong correlations with patient symptoms pointing at novel therapeutic opportunities.},
}
@article {pmid40725611,
year = {2025},
author = {Akiyama, H and Sakurada, Y and Honda, H and Matsuda, Y and Otsuka, Y and Tokumasu, K and Nakano, Y and Takase, R and Omura, D and Ueda, K and Otsuka, F},
title = {Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
pmid = {40725611},
issn = {2077-0383},
support = {23fk0108585h0001//AMED/ ; Research Grant//Japanese Society of Hospital General Medicine/ ; },
abstract = {Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences.},
}
@article {pmid40725569,
year = {2025},
author = {Durak, G and Akin, K and Cetin, O and Uysal, E and Aktas, HE and Durak, U and Karkas, AY and Senkal, N and Savas, H and Tunaci, A and Medetalibeyoglu, A and Bagci, U and Erturk, SM},
title = {Radiologic and Clinical Correlates of Long-Term Post-COVID-19 Pulmonary Sequelae.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
pmid = {40725569},
issn = {2077-0383},
support = {R01-HL171376//Radiological Society of North America/ ; },
abstract = {Background/Objectives: The long-term sequelae of COVID-19 pneumonia, particularly the persistence of imaging abnormalities and their relationship to clinical symptoms, remain unclear. While the acute radiologic patterns are well-documented, the transition to chronic pulmonary changes-and their implications for long COVID symptoms-require systematic investigation. Methods: Our study included 93 patients with moderate to severe COVID-19 pneumonia who were admitted to Istanbul Medical Faculty Hospital, each having one follow-up CT scan over a ten-month period. Two thoracic radiologists independently calculated semi-quantitative initial chest CT scores to evaluate lung involvement in pneumonia (0-5 per lobe, total score 0-25). Two radiologists and one pulmonologist retrospectively examined the persistence of follow-up imaging findings, interpreting them alongside the relevant clinical and laboratory data. Additionally, in a subcohort (n = 46), mid-term (5-7 months) and long-term (≥10 months) scans were compared to assess temporal trajectories. Results: Among the 93 patients with long-term follow-up imaging, non-fibrotic changes persisted in 34 scans (36.6%), while fibrotic-like changes were observed in 70 scans (75.3%). The most common persistent non-fibrotic changes were heterogeneous attenuation (29%, n = 27) and ground-glass opacities (17.2%, n = 16), and the persistent fibrotic-like changes were pleuroparenchymal bands or linear atelectasis (58%, n = 54), fine reticulation (52.6%, n = 49), and subpleural curvilinear lines (34.4%, n = 32). Both persistent non-fibrotic and fibrotic-like changes were statistically correlated with the initial CT score (p < 0.001), LDH (p < 0.001), and ferritin levels (p = 0.008 and p = 0.003, respectively). Fatigue (p = 0.025) and chest pain (p < 0.001) were reported more frequently in patients with persistent non-fibrotic changes, while chest pain (p = 0.033) was reported more frequently among those with persistent fibrotic-like changes. Among the 46 patients who underwent both mid- and long-term follow-up imaging, 47.2% of those with non-fibrotic changes (17 out of 36) and 10% of those with fibrotic-like changes (4 out of 40) exhibited regression over the long term. Conclusions: Initial imaging and laboratory findings may indicate persistent imaging findings related to long-term sequelae of COVID-19 pneumonia. Many of these persistent imaging abnormalities, particularly non-fibrotic changes seen in the mid-term, tend to lessen over the long term. A correlation exists between persistent imaging findings and clinical outcomes of long COVID-19, underscoring the need for further research.},
}
@article {pmid40724994,
year = {2025},
author = {Hofmann, S and Lucio, M and Wallukat, G and Hoffmanns, J and Schröder, T and Raith, F and Szewczykowski, C and Skornia, A and Rech, J and Schottenhamml, J and Harrer, T and Ganslmayer, M and Mardin, C and Flecks, M and Lakatos, P and Hohberger, B},
title = {Functional Autoantibodies Targeting G-Protein-Coupled Receptors and Their Clinical Phenotype in Patients with Long-COVID.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
pmid = {40724994},
issn = {1422-0067},
support = {01EP2108A//German Federal Ministry of Research, Technology and Space (BMFTR): reCOVer/ ; 01EO2105//iIMMUNE_ACS/ ; 2490-PC-2021-V14//Bavarian Health and Food Safety Authority (LGL): discover/ ; },
mesh = {Humans ; *Autoantibodies/immunology/blood ; Male ; Female ; *Receptors, G-Protein-Coupled/immunology ; Middle Aged ; Adult ; *COVID-19/immunology ; Aged ; Phenotype ; SARS-CoV-2/immunology ; },
abstract = {Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1-7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms.},
}
@article {pmid40724930,
year = {2025},
author = {Maiti, AK},
title = {In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
pmid = {40724930},
issn = {1422-0067},
mesh = {Humans ; *Polymorphism, Single Nucleotide ; *COVID-19/genetics/complications ; *Lung/physiopathology/metabolism/pathology ; SARS-CoV-2 ; Computer Simulation ; *Brain/physiopathology/metabolism ; RNA, Long Noncoding/genetics/metabolism/chemistry ; Computational Biology ; Genetic Predisposition to Disease ; Transcription Factors/metabolism ; },
abstract = {Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10[-10], OR = 1.63, 95% CI: 1.40-1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery.},
}
@article {pmid40724879,
year = {2025},
author = {Peppercorn, K and Sharma, S and Edgar, CD and Stockwell, PA and Rodger, EJ and Chatterjee, A and Tate, WP},
title = {Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
pmid = {40724879},
issn = {1422-0067},
support = {no number//Brain Research New Zealand/ ; no number given//Brain Research New Zealand/ ; no number//ANZMES/ ; no numbers//Private donations/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/genetics/blood ; *DNA Methylation ; Male ; Female ; *COVID-19/genetics/blood ; Middle Aged ; Adult ; Leukocytes, Mononuclear/metabolism ; SARS-CoV-2 ; Epigenesis, Genetic ; Case-Control Studies ; Principal Component Analysis ; },
abstract = {Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC). Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation. A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort. Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance.},
}
@article {pmid40723876,
year = {2025},
author = {Richardson, E and Mo, CC and Calabretta, E and Corrado, F and Kocoglu, MH and Baron, RM and Connors, JM and Iacobelli, M and Wei, LJ and Benjamin, EJ and Rapoport, AP and Díaz-Ricart, M and Martínez-Mellado, AJ and Carlo-Stella, C and Richardson, PG and Moraleda, JM},
title = {Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.},
journal = {Biomolecules},
volume = {15},
number = {7},
pages = {},
pmid = {40723876},
issn = {2218-273X},
mesh = {Humans ; *Hematologic Neoplasms/drug therapy/complications/pathology ; *Polydeoxyribonucleotides/therapeutic use/pharmacology ; *COVID-19/complications/pathology/virology ; SARS-CoV-2 ; Hepatic Veno-Occlusive Disease/drug therapy ; *COVID-19 Drug Treatment ; Graft vs Host Disease/drug therapy ; Cytokine Release Syndrome/drug therapy ; *Fibrinolytic Agents/therapeutic use/pharmacology ; },
abstract = {Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide's potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection ("long-COVID"), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action.},
}
@article {pmid40723800,
year = {2025},
author = {Tobi, M and Chaudhari, D and Ryan, EP and Rossi, NF and Koka, O and Baxter, B and Tipton, M and Dutt, TS and Tobi, Y and McVicker, B and Angoa-Perez, M},
title = {Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles.},
journal = {Biomolecules},
volume = {15},
number = {7},
pages = {},
pmid = {40723800},
issn = {2218-273X},
support = {Merit Review Grant Awards (MT) and a Merit R&amp;D #BX004127 (B.H.M. and M.T.)./VA/VA/United States ; },
mesh = {Humans ; *COVID-19/immunology/complications/blood/microbiology ; *Fatigue Syndrome, Chronic/immunology/blood/microbiology ; *Cytokines/blood ; *Feces/microbiology ; Male ; Female ; Middle Aged ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Adult ; Post-Acute COVID-19 Syndrome ; Biomarkers/blood ; },
abstract = {While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual Bacillota and Bacteroidota species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (p < 0.02); IL10 versus IL-12p70a (p < 0.02); IL-1b versus IL-6 (p < 0.01); MCP1 versus TARC (p < 0.03); IL-8 versus TARC (p < 0.002); and Eotaxin3 versus TARC (p < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (p < 0.01); TNF-α versus IL-1-β (p < 0.06); MCP4 versus TARC (p < 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology.},
}
@article {pmid40722688,
year = {2025},
author = {Ruas, CM and Silva, ML and Figueiredo, ALGF and Alencar, AP and Melo, SS and Castro, GF and Carobin, NV and Cordeiro, MA and Aguirre, JFR and Oliveira, AFM and Sabino, AP},
title = {Long COVID and Its Impacts: A Case-Control Study in Brazil.},
journal = {Biomedicines},
volume = {13},
number = {7},
pages = {},
pmid = {40722688},
issn = {2227-9059},
support = {27968*17 - FINEP/RTR/PRPq/REDE COVID-19 - UFMG - LINBIO//MCTI/FINEP/ ; },
abstract = {Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is to compare symptom prevalence between infected individuals pre and post-COVID-19 and non-infected individuals in a population from Southeastern Brazil. Materials and Methods: A case-control study was conducted with participants from the MonitoraCovid program in a university in Brazil. The study included adults who responded to a questionnaire about long COVID symptoms. Data were collected virtually between October 2023 and May 2024. Results: Of the 2886 individuals eligible for analysis, 75.5% reported having been positive for COVID-19. Most participants were vaccinated, with 82.99% receiving two doses. In the pre and post comparison, individuals who had COVID-19 were more likely to report increased symptoms after infection, with 95.5% of assessed conditions worsening, particularly cognitive and respiratory issues. A comparison between those who had and had not been infected with COVID-19 showed that only 6.67% of symptoms were more prevalent in the infected group. The most significant post-COVID-19 symptoms included memory problems, fatigue, and shortness of breath, though some conditions, such as anxiety and sleep disturbances, were less common among those who had COVID-19. Conclusions: The findings reinforce that long COVID significantly impacts cognitive health, highlighting the importance of monitoring previously infected individuals. The study also emphasizes the need for further research in Global South contexts to better understand the long-term implications of COVID-19.},
}
@article {pmid40722521,
year = {2025},
author = {Krljanac, G and Asanin, M and Viduljevic, M and Stankovic, S and Simatovic, K and Lasica, R and Nedeljkovic-Arsenovic, O and Maksimovic, R and Zagorac, S and Savic-Radojevic, A and Djukic, T and Stevanovic, G and Pavlovic, V and Simic, T},
title = {Cardiovascular Manifestations of Patients with Long COVID.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
pmid = {40722521},
issn = {2075-4418},
abstract = {Background: This study investigates the potential mechanisms behind changes in cardiac structure and function in long COVID patients. Methods: This study involved 176 consecutive outpatients in follow-up care (average age 55.9 years; 58.5% male) who experienced symptoms for over 12 weeks (average 6.2 ± 2.7 months), following coronavirus infection (COVID-19). Results: The patients with long COVID and cardiovascular manifestations were significantly more hospitalized (88.5% vs. 75.9%) and had longer hospital stays. Significant echocardiography changes were observed in the left ventricular ejection fraction (LVEF) (59.6 ± 5.4% vs. 62.5 ± 3.8%); longitudinal strain (LS) in the sub-endocardium and intra-myocardium layers (-20.9 vs. -22.0% and -18.6 vs. -19.5%); circumferential strain (CS) in the sub-epicardium layers (-9.6 vs. -10.5%); and CS post-systolic shortening (CS PSS) (0.138 vs. 0.088 s). Additionally, pathological cardiac magnetic resonance (CMR) findings were seen in 58.2% of the group of patients with long COVID and cardiovascular manifestation; 43.3% exhibited positive late gadolinium enhancement (LGE), 21.0% had elevated native T1 mapping, and 22.4% had elevated native T2 mapping. Conclusions: Most patients with long COVID showed structural and functional changes in their cardiovascular systems, primarily caused by prolonged inflammation. Using multimodality imaging is important for uncovering the mechanisms to predict chronic myocarditis, early-stage heart failure, and pre-ischemic states, which can lead to serious complications. Recognizing the specific cardiovascular phenotypes associated with long COVID is essential in order to provide timely and appropriate treatment.},
}
@article {pmid40721817,
year = {2025},
author = {Yogendra, R and Perlowski, A and Johng, B and Dahshan, H and Orr, C and Jeffers, D and Husain, K and Patterson, BK},
title = {Perioperative and anesthetic considerations for post-acute sequelae of COVID (PASC)/long COVID.},
journal = {Perioperative medicine (London, England)},
volume = {14},
number = {1},
pages = {80},
pmid = {40721817},
issn = {2047-0525},
abstract = {Post-acute sequelae of COVID (PASC), commonly known as long COVID, presents with a broad spectrum of medical conditions and symptoms persisting beyond 3 months post-SARS-CoV-2 infection, affecting over 18 million Americans and 65 million people worldwide. Despite its prevalence, to date, there are no specific clinical guidelines for the perioperative management of PASC patients. PASC is a complex, multisystemic condition leading to neurological, respiratory, and endocrine sequelae, potentially resulting from persistent viral presence, immune dysregulation, and/or end-organ damage. This manuscript discusses the implications of these sequelae on anesthesia practice, emphasizing the need for vigilance in pre-operative assessments to identify PASC and associated conditions through detailed patient history, understanding of off-label medication use, and familiarity with medical terminologies like POTS, MCAS, and brain fog. Key perioperative considerations include cautious use of anesthetics, especially in patients with neurological and cardiovascular complications. Pulmonary management strategies for PASC patients, such as lung-protective ventilation and non-invasive post-operative support, could mitigate any perioperative respiratory complications. Finally, we underscore the importance of a multidisciplinary approach to manage PASC patients effectively during surgery, advocating for personalized anesthetic plans and calling for more evidence-driven guidelines for this emerging patient group as research progresses.},
}
@article {pmid40721715,
year = {2025},
author = {Durieux, JC and Koberssy, Z and Daher, J and Baissary, J and Abboud, M and Atieh, O and Woolverton, C and McComsey, GA},
title = {Sex differences in inflammation and markers of gut integrity in long COVID.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27374},
pmid = {40721715},
issn = {2045-2322},
support = {UM1 TR004528/TR/NCATS NIH HHS/United States ; UM1TR004528//Clinical and Translational Science Collaborative of Northern Ohio, funded by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/complications/pathology ; Adult ; *Inflammation ; Middle Aged ; Biomarkers/metabolism/blood ; Sex Factors ; SARS-CoV-2 ; Sex Characteristics ; },
abstract = {Endothelial damage represents an essential pathogenic mechanism of respiratory and multiorgan dysfunction as seen in the post-acute phase of COVID-19. Biological differences between male and female sex, inflammation, and gut integrity may have an integral role in endothelial damage and explain the residual effects of COVID-19 infection in long COVID, yet evidence is limited. Confirmed COVID-19 negative participants were 1:1 propensity-score matched to COVID-19 positive participants. Symptoms occurring at least one-month following COVID-infection and lasting more than three-months was defined as long COVID. Measures of endothelial function included reactive hyperemic index (RHI ≥ 1.67 = normal endothelial function) and augmentation index (higher AIx = worse arterial elasticity). A total of 89 COVID-19 negative participants was matched to 89 COVID-19 positive participants. Among the COVID-19 survivors, the median age was 42.92 years, 46.07% were female sex, and 57 (64%) had long COVID. Higher levels of inflammation (TNF-RI and oxLDL) and gut integrity (zonulin and BDG) was associated (P < 0.05) with a two-fold increase in the odds of long COVID. Female sex, independent of COVID-19 status, was 4x more likely to have worse AIx (P < 0.0001) compared to male sex. Among female sex with long COVID, higher levels of inflammation (IL-6, VCAM, hsCRP) and gut integrity (zonulin) was independently associated (P < 0.05) with higher AIx. Female sex with long COVID symptoms had the worse inflammation, gut integrity, and arterial stiffness among COVID-19 survivors. This reinforces the importance of continued, long-term follow-up care following COVID-19 infection, with special attention needed for female sex who may be at a higher cardiovascular disease risk.},
}
@article {pmid40721590,
year = {2025},
author = {Berry, M and Kong, AM and Paredes, R and Paone, J and Shah, R and Taylor, R and Mozaffari, E and Gupta, R and Gottlieb, RL and Mateu, L and Abdelghany, M and Goldman, JD and Chokkalingam, AP},
title = {Risk of Long COVID in hospitalized individuals treated with remdesivir for acute COVID-19.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27441},
pmid = {40721590},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; *COVID-19 Drug Treatment ; Retrospective Studies ; Middle Aged ; Aged ; *Alanine/analogs &amp; derivatives/therapeutic use ; Hospitalization ; *COVID-19/epidemiology/complications/virology ; *Antiviral Agents/therapeutic use ; *Adenosine Monophosphate/analogs &amp; derivatives/therapeutic use ; SARS-CoV-2 ; Adult ; Immunocompromised Host ; Aged, 80 and over ; Young Adult ; Risk Factors ; Adolescent ; },
abstract = {Long COVID comprises a multisystem syndrome occurring after COVID-19. This retrospective cohort study investigated whether remdesivir given during acute COVID-19 is associated with reduced incidence of Long COVID, including in immunocompromised subgroups. The HealthVerity database of hospital chargemaster data linked to closed claims was queried for patients aged ≥ 12 years hospitalized for ≥ 2 days with COVID-19 between May 1, 2020, and September 30, 2021. Relative risk between remdesivir-exposed and unexposed patients was calculated for 16 individual Long COVID outcomes and a composite of any Long COVID outcome, occurring 90-270 days after hospital admission. Subgroup analyses occurred in immunocompromised patients. Regression models accounted for censoring, competing risks, and treatment assignment weights; statistical inferences were adjusted for multiple comparisons. Among 3,661,303 hospitalized patients, 52,006 with COVID-19 were included; 20,246 (38.9%) were immunocompromised. In the overall and immunocompromised populations, respectively, 33.0% and 29.5% received remdesivir; the composite of ≥ 1 Long COVID outcome occurred in 55.5% and 62.9%. Patients administered remdesivir experienced lower risk of any Long COVID outcome (risk ratio, 0.96; 95% CI 0.94-0.97; adjusted P < 0.001). Risk for several individual Long COVID outcomes was lower in those receiving remdesivir in the overall and immunocompromised populations. In conclusion, exposure to remdesivir was associated with a lower risk of Long COVID.},
}
@article {pmid40721474,
year = {2025},
author = {Chong, KC and Wei, Y and Jia, KM and Boyer, C and Lin, G and Wang, H and Li, C and Hung, CT and Jiang, X and Yam, CHK and Chow, TY and Wang, Y and Zhao, S and Li, K and Yang, A and Mok, CKP and Hui, DS and Yeoh, EK and Guo, Z},
title = {SARS-CoV-2 rebound and post-acute mortality and hospitalization among patients admitted with COVID-19: cohort study.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6924},
pmid = {40721474},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/mortality/virology ; Male ; Female ; *SARS-CoV-2/drug effects/isolation &amp; purification/physiology ; *Hospitalization/statistics &amp; numerical data ; Middle Aged ; Ritonavir/therapeutic use ; Aged ; Hong Kong/epidemiology ; Antiviral Agents/therapeutic use ; Cohort Studies ; COVID-19 Drug Treatment ; Hydroxylamines/therapeutic use ; Leucine/analogs &amp; derivatives/therapeutic use ; Cytidine/analogs &amp; derivatives/therapeutic use ; Adult ; Post-Acute COVID-19 Syndrome ; Morpholines/therapeutic use ; Viral Load ; },
abstract = {Recent investigations have demonstrated a relationship between the persistence of SARS-CoV-2 and post-COVID-19 conditions. Building upon a potential connection between SARS-CoV-2 persistence and early virologic rebound, we examine the association of early virologic rebound with post-acute mortality and hospitalization due to post-acute sequelae among hospitalized patients with COVID-19 in Hong Kong. Our study includes 13,859, 3959, and 4502 patients in the all-patient, nirmatrelvir/ritonavir, and molnupiravir group, respectively. Results show that patients who experienced virologic rebound exhibited a significantly higher risk of post-acute mortality (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.36-1.70) with a risk difference [RD] of 7.19%, compared with patients without virologic rebound. A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41-2.25; RD, 12.55%) and molnupiravir-treated patients (HR, 1.47; 95% CI, 1.18-1.82; RD, 4.90%). The virologic rebound may thus serve as an early marker for post-COVID-19 condition, enabling healthcare officials to monitor and provide timely intervention for long COVID.},
}
@article {pmid40721458,
year = {2025},
author = {Meister, T and Maiväli, &#xdc; and Tenson, K and Tisler, A and Kalda, R and Suija, K and Uusküla, A},
title = {Dynamic effects of COVID-19 vaccination on major acute cardiovascular events and mortality following SARS-CoV-2 infection in a target trial emulation study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27530},
pmid = {40721458},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/mortality/prevention &amp; control/complications ; Middle Aged ; Aged ; Female ; Male ; Adult ; *Cardiovascular Diseases/mortality/epidemiology/etiology ; Aged, 80 and over ; SARS-CoV-2/immunology ; *COVID-19 Vaccines/administration &amp; dosage ; *Vaccination ; },
abstract = {The COVID-19 pandemic presents significant health challenges, including increased risk of mortality and long-term complications. While vaccination has proven remarkably effective in mitigating severe disease and mortality associated with acute COVID-19 infection, the long-term implications of vaccination, particularly its influence on post-COVID cardiovascular events and the temporal dynamics of such effects, remain poorly understood. This target trial emulation study utilizes real-world electronic medical record data from April 2021 to March 2023 to address this gap. We evaluate the effect of pre-infection COVID-19 vaccination on the risk of major acute cardiovascular events (MACE) and all-cause mortality in individuals aged 40-85 years during one year after SARS-CoV-2 infection. Among individuals with COVID-19 (n = 18,223 vaccinated, n = 15,331 not vaccinated), vaccination provided a significant protective effect against MACE (weighted incidence rate ratio [wIRR] 0.71, 95% CI 0.58-0.84) and all-cause mortality (wIRR 0.32, 95% CI 0.28-0.36). This effect persisted for approximately three months after the acute infection. These findings underscore the importance of COVID-19 vaccination in reducing both short-term and long-term health risks associated with the infection.},
}
@article {pmid40721391,
year = {2025},
author = {Shi, L and Tian, X and Lu, X and Yih, B and Chen, J},
title = {Frailty in Alzheimer's disease: A bibliometric analysis of research hotspots, emerging trends, and knowledge structure.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {107},
number = {2},
pages = {597-616},
doi = {10.1177/13872877251362665},
pmid = {40721391},
issn = {1875-8908},
mesh = {Humans ; *Alzheimer Disease/complications/epidemiology ; *Bibliometrics ; *Frailty/epidemiology ; },
abstract = {BackgroundFrailty has emerged as a major public health concern in aging populations, particularly among individuals with Alzheimer's disease (AD), where it exacerbates adverse outcomes and signals dementia progression. While research on frailty in AD has grown rapidly, a thorough analysis of key research hotspots and trends remains insufficient.ObjectiveThis study employs bibliometric methods to systematically explore core themes, identify potential frontiers and emerging directions in this field.MethodsOn December 27, 2024, a comprehensive search was conducted in the Web of Science Core Collection (WoSCC) database using keywords associated with frailty in AD. Bibliometric and knowledge mapping analyses were carried out using CiteSpace, VOSviewer, and R software.ResultsBetween 2005 and 2024, a total of 915 publications on frailty in AD were produced by 5950 researchers from 2084 institutions spanning 70 countries. Recent research in this field predominantly focuses on disciplines such as molecular biology, neuroscience, and pharmacology. Current studies emphasize interventions for frailty in patients with AD and the investigation of underlying pathological mechanisms, particularly concerning nutritional status and the influence of long COVID on frailty in AD. Emerging research themes include intervention strategies, mouse models, effects of long COVID, nutritional factors, mechanistic studies, brain fog, and subjective cognitive decline.ConclusionsThis bibliometric analysis highlights research frontiers on frailty in AD, emphasizing early monitoring and management of frailty are pivotal approaches to decelerate AD progression and improve patient outcomes. These findings offer valuable insights for future research, helping to address critical needs in patient care and disease management.},
}
@article {pmid40720313,
year = {2025},
author = {Andrejow, NW and Reidy, TG and Billups, K and Mougianis, ID and Birnie, KA and Ploetz, D and Carney, J},
title = {Adapting an Intensive Interdisciplinary Chronic Pain Rehabilitation Program to Address Long COVID in Youth: A Pilot Study.},
journal = {American journal of physical medicine &amp; rehabilitation},
volume = {104},
number = {10},
pages = {e153-e156},
doi = {10.1097/PHM.0000000000002807},
pmid = {40720313},
issn = {1537-7385},
mesh = {Adolescent ; Child ; Female ; Humans ; Male ; Activities of Daily Living ; *Chronic Pain/rehabilitation/psychology ; *COVID-19/complications ; *Pain Management/methods ; Pandemics ; *Patient Care Team/organization &amp; administration ; Pilot Projects ; },
abstract = {During the COVID-19 pandemic, an established interdisciplinary pain program pivoted to address the emerging needs of youth with long COVID. The program used a rehabilitation model with an overarching goal of supporting youth in their return to school, activities of daily living, and social-emotional functioning by learning to cope with chronic pain and mitigate its impact on daily life. This article describes that protocol and uses three patient cases to illustrate positive clinical changes in function and the lessons learned from adapting the Interdisciplinary Pain Program to pediatric patients with long COVID.},
}
@article {pmid40717948,
year = {2025},
author = {Lapin, B and Baker, S and Thompson, N and Li, Y and Milinovich, A and Lago, W and Katzan, I},
title = {Pre-COVID health-related quality of life predicts symptoms and outcomes for patients with long COVID.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1581288},
pmid = {40717948},
issn = {2296-2565},
mesh = {Humans ; *Quality of Life/psychology ; Female ; Male ; Middle Aged ; *COVID-19/complications/psychology/epidemiology ; Retrospective Studies ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Propensity Score ; SARS-CoV-2 ; Surveys and Questionnaires ; Health Status ; },
abstract = {BACKGROUND: Post-acute sequelae SARS-CoV-2 (PASC) is a prevalent condition with variable symptom presentation. PASC occurs more often with pre-existing medical conditions, however it is unknown whether pre-COVID health-related quality of life (HRQL) is associated with PASC. Similarly, the trajectory of HRQL following PASC is unknown.<br><br>OBJECTIVE: Our study sought to evaluate (1) whether pre-COVID HRQL is associated with PASC symptoms; (2) whether PASC patients have worse pre-COVID HRQL compared to matched controls; and (3) to compare HRQL trajectories from pre-COVID to 1-year follow-up between PASC patients and matched controls.<br><br>DESIGN: Retrospective cohort study with propensity-score matched control group.<br><br>PARTICIPANTS: The cohort included 1,114 adult patients (mean age 53 &#xb1; 14, 75% female) seen in a PASC clinic between 2/10/21 and 3/27/24 who completed HRQL surveys prior to their initial COVID-diagnosis in a large health system. A propensity-score matched control group included patients with COVID-19 without PASC.<br><br>MAIN MEASURES: HRQL was measured with PROMIS Global Health [global mental health (GMH) and global physical health (GPH) summary scores].<br><br>KEY RESULTS: PASC symptoms were significantly associated with pre-COVID HRQL. Symptoms most associated with PROMIS-GMH included diarrhea/nausea [odds ratio (OR) = 1.27 (95% CI: 1.16-1.39) per five-point worsening] and brain fog [OR = 1.25 (95% CI: 1.14-1.37)], while fatigue [OR = 1.39 (95% CI: 1.15-1.68)] had the highest association with PROMIS-GPH. Pre-COVID GMH and GPH were significantly worse for PASC patients compared to controls [-2.6 (SE 0.4) and -3.4 (0.3) T-score points, respectively]. At 1-year following COVID, PASC patients worsened significantly in GMH and GPH (-2.0 &#xb1; 8.2 and -1.2 &#xb1; 7.5 T-score points, respectively), compared to controls who worsened significantly on GMH but not GPH (-0.8 &#xb1; 7.7 and 0.2 &#xb1; 7.4 T-score points, respectively).<br><br>CONCLUSIONS: In patients with PASC, worse pre-COVID HRQL was associated with more PASC-related symptoms. PASC patients had worse pre-COVID HRQL compared to matched controls and experienced a greater decline in HRQL 1-year after COVID-diagnosis; however, this decline was below the threshold for clinical significance.},
}
@article {pmid40717478,
year = {2025},
author = {Bajić, D and Todorović, N and Popović, ML and Plazačić, M and Mihajlović, A},
title = {Immunity's core reset: Synbiotics and gut microbiota in the COVID-19 era.},
journal = {Innate immunity},
volume = {31},
number = {},
pages = {17534259251362023},
pmid = {40717478},
issn = {1753-4267},
mesh = {Humans ; *COVID-19/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Synbiotics/administration &amp; dosage ; *SARS-CoV-2/immunology ; *Dysbiosis/immunology/microbiology ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Inflammation/immunology ; },
abstract = {The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis-an imbalance in gut bacteria-that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics-combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)-are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.},
}
@article {pmid40710029,
year = {2025},
author = {Yu, L and McCracken, LM},
title = {The Association Between COVID-19-Related Persistent Symptoms, Psychological Flexibility, and General Mental Health Among People With and Without Persistent Pain in the UK.},
journal = {Clinics and practice},
volume = {15},
number = {7},
pages = {},
pmid = {40710029},
issn = {2039-7275},
abstract = {Objectives: Persistent symptoms following COVID-19 may adversely impact the general mental health of people with chronic pain, and psychological flexibility may buffer these impacts. However, it remains unclear whether such lasting implications of COVID-19 differ between people with and without chronic pain. This study investigated the relationships between persistent symptoms post-COVID-19, psychological flexibility, and general mental health among people with and without persistent pain during the COVID-19 pandemic in the UK. Methods: A total of 204 adults living in the UK were recruited via social media and completed an online survey, including measures of persistent symptoms, depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), insomnia (the Insomnia Severity Index), and psychological flexibility (the Multidimensional Psychological Flexibility Inventory), and were included in the analyses. Results: Participants with persistent pain (n = 70) experienced more-persistent symptoms, poorer general mental health, and a higher level of psychological inflexibility compared with participants without persistent pain (n = 133). Overall, the relationships between persistent physical symptoms, general mental health, and psychological (in)flexibility showed similar patterns in the two groups. Participants with more-persistent physical symptoms experienced significantly poorer general mental health. Furthermore, people with higher levels of psychological inflexibility reported worse general mental health. There was little evidence that psychological (in)flexibility could "buffer" the association between persistent physical symptoms and general mental health. Conclusions: People with chronic pain appear more vulnerable to persistent symptoms and reduced general mental health compared with people without pain. Treatments that reduce psychological inflexibility, such as ACT, may improve outcomes for people with persistent symptoms post-COVID-19.},
}
@article {pmid40709992,
year = {2025},
author = {Crespo-Barrios, J},
title = {Vaxtherapy, a Multiphase Therapeutic Protocol Approach for Longvax, the COVID-19 Vaccine-Induced Disease: Spike Persistence as the Core Culprit and Its Downstream Effects.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {7},
pages = {},
pmid = {40709992},
issn = {2079-9721},
abstract = {Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management.},
}
@article {pmid40708634,
year = {2025},
author = {Aktaş, AR},
title = {Interaction of SARS-CoV-2 and SARS-CoV-2 vaccines with renin angiotensin aldosterone system, clinical outcomes, and angiotensin (1-7) as a physiological treatment recommendation: hypothesis and theory article.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1612442},
pmid = {40708634},
issn = {2296-858X},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected all of humanity since the first case was reported and spread rapidly around the world, creating a pandemic. Despite the repurposing of many drugs and the development of vaccines, effective treatment and protection are limited. In addition, SARS-CoV-2 continues to be a current public health problem with complications, identifying cases of long-term Covid syndrome, and detection of vaccine-related adverse events. It can be said that the most important factor underlying all these problems is that the interaction between SARS-CoV-2 and renin-angiotensin-aldosterone system (RAAS) is not completely understood despite extensive research. Although different disciplines have limited determinations from their own perspectives regarding the communication with RAAS, it has not been sufficiently expressed in a way to see the whole picture. In this study, it is tried to see the whole picture in the interaction of RAAS and SARS-CoV-2. It is detected inadequacies in treatments and interactions that may be design errors in vaccines. These determinations also show that our templates for producing treatments are not sufficient. For this reason, we have to develop our templates with what we have learned specifically about SARS-CoV-2. Considering the accuracy of our hypothesis on the SARS-CoV-2 - RAAS relationship, Ang(1-7) can be considered a strong option for treatment. Although the SARS-CoV-2 pandemic seems to be over, epidemics and even new pandemics are likely to occur with new mutations.},
}
@article {pmid40708533,
year = {2025},
author = {Chau, SWH and Chue, TM and Lam, TC and Lai, YL and Chan, RNY and Wong, PWC and Li, SX and Liu, Y and Chan, JWY and Chan, PK and Lai, CK and Leung, TWH and Wing, YK},
title = {Chronic post-COVID neuropsychiatric symptoms persisting more than 1 year after infection during the 'Omicron wave'.},
journal = {BJPsych open},
volume = {11},
number = {4},
pages = {e160},
pmid = {40708533},
issn = {2056-4724},
abstract = {BACKGROUND: The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.<br><br>AIMS: To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the 'Omicron wave' and discover phenotypes of patients based on their symptoms' patterns using a pre-registered protocol.<br><br>METHOD: We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.<br><br>RESULTS: Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint-fatigue and anxiety-depression) and a minor headache-dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint-fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint-fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.<br><br>CONCLUSIONS: Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.},
}
@article {pmid40708204,
year = {2025},
author = {Malerba, M and Purghè, B and Ragnoli, B and Manfredi, M and Baldanzi, G},
title = {Molecular profiling of exhaled breath condensate in respiratory diseases.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2537910},
pmid = {40708204},
issn = {1365-2060},
mesh = {Humans ; Breath Tests/methods ; *COVID-19/metabolism/diagnosis ; Metabolomics/methods ; Proteomics/methods ; SARS-CoV-2 ; Exhalation ; Pulmonary Disease, Chronic Obstructive/diagnosis/metabolism ; Asthma/diagnosis/metabolism ; Mass Spectrometry/methods ; Biomarkers/analysis ; *Respiratory Tract Diseases/diagnosis/metabolism ; },
abstract = {BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways.<br><br>AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19).<br><br>RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors.<br><br>CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.},
}
@article {pmid40707035,
year = {2025},
author = {Meagher, T},
title = {Long Covid in Year 5: Some Progress, Still Many Questions.},
journal = {Journal of insurance medicine (New York, N.Y.)},
volume = {52},
number = {2},
pages = {61-65},
doi = {10.17849/insm-52-2-1-5.2},
pmid = {40707035},
issn = {0743-6661},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Long Covid was first described in 2020. Five years later, progress in disease characterization has been considerable, and definitions continue to evolve. Several disease mechanisms are under study, and evidence for multiple endotypes is accumulating. No clinical biomarker has been identified, nor has an effective therapy been developed. Overlap with other post-infectious syndromes, particularly myalgic encephalomyelitis/chronic fatigue syndrome, is now more evident. For most individuals, symptoms of long Covid progressively disappear over time. Recurrent Covid-19 infections are now an important contributor to the pool of affected individuals. While symptoms limit activity in as many as 20%, inability to work is less common. The anticipated surge of disability claims from insured individuals has not materialized.},
}
@article {pmid40705709,
year = {2025},
author = {Sauter, KA and Webb, GM and Bader, L and Kreklywich, CN and Takahashi, DL and Zaro, C and McGuire, CM and Lewis, AD and Colgin, LMA and Kirigiti, MA and Blomenkamp, H and Pessoa, C and Humkey, M and Hulahan, J and Sleeman, M and Zweig, RC and Thomas, S and Thomas, A and Gao, L and Hirsch, AJ and Levy, M and Cherry, S and Kahn, SE and Slifka, MK and Streblow, DN and Sacha, JB and Kievit, P and Roberts, CT},
title = {Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.},
journal = {PLoS pathogens},
volume = {21},
number = {7},
pages = {e1012988},
pmid = {40705709},
issn = {1553-7374},
support = {P30 DK017047/DK/NIDDK NIH HHS/United States ; P51 OD011092/OD/NIH HHS/United States ; },
mesh = {Animals ; *COVID-19/complications/immunology/virology/pathology ; *Obesity/complications/immunology/virology ; Macaca mulatta ; Male ; *SARS-CoV-2/immunology ; Antibodies, Viral/blood/immunology ; Disease Models, Animal ; Post-Acute COVID-19 Syndrome ; Cytokines ; },
abstract = {Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.},
}
@article {pmid40704727,
year = {2025},
author = {Yeh, AY and Chao, YY and Strauss, SM and Chou, CC},
title = {Association Between COVID-19 Infection and Subjective Cognitive Decline in Adults: A Cross-Sectional Online Survey Study.},
journal = {Western journal of nursing research},
volume = {47},
number = {9},
pages = {854-864},
doi = {10.1177/01939459251350812},
pmid = {40704727},
issn = {1552-8456},
mesh = {Humans ; Cross-Sectional Studies ; Female ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology/psychology ; Male ; Adult ; Surveys and Questionnaires ; Middle Aged ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Cognitive impairment is the most common residual symptom following COVID infection, reported in approximately 22% of adults diagnosed with COVID-19. Subjective cognitive decline is considered a significant early indicator of the progression of Alzheimer's disease. There is limited research investigating subjective cognitive decline following COVID-19 infection.<br><br>PURPOSE: The purpose of this study was to examine the relationship between COVID-19 infection and subjective cognitive decline in adults.<br><br>METHODS: In this comparative and cross-sectional study, data were collected via an online survey involving 98 adults diagnosed with COVID-19 and 317 adults never diagnosed with COVID-19. The mean age of participants was 30.2&#x2009;&#xb1;&#x2009;8.4&#x2009;years, and 36.6% were female. The revised Everyday Cognition Scale was used to assess subjective cognitive decline. Data analysis included descriptive statistics, one-way analysis of covariance, and hierarchical multiple regression.<br><br>RESULTS: After controlling for covariates, adults diagnosed with COVID-19 experienced significantly greater subjective declines in memory (P&#x2009;=&#x2009;.002), language (P&#x2009;=&#x2009;.002), organizational ability (P&#x2009;=&#x2009;.03), attention (P&#x2009;=&#x2009;.003), and global cognition (P&#x2009;=&#x2009;.007) than those never diagnosed with COVID-19. Furthermore, COVID-19 diagnosis was a significant predictor of worse subjective declines in these domains of cognition.<br><br>CONCLUSION: Findings highlight the associations between COVID-19 infection and subjective cognitive decline across various domains. These results underscore the need for longitudinal studies to explore the progression of cognitive decline. Early detection and management of cognitive dysfunction can prevent further deterioration of cognitive function.},
}
@article {pmid40703523,
year = {2025},
author = {Girgis, AA and Cimbro, R and Yang, T and Rebman, AW and Sewell, T and Villegas de Flores, D and Vadalia, A and Robinson, WH and Cox, AL and Darrah, E and Soloski, MJ and Aucott, J},
title = {Aberrant T-cell phenotypes in a cohort of patients with post-treatment Lyme disease.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1607619},
pmid = {40703523},
issn = {1664-3224},
mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; Immunophenotyping ; Aged ; Phenotype ; Cytokines ; *Post-Lyme Disease Syndrome/immunology ; *Lyme Disease/immunology ; Cohort Studies ; *T-Lymphocyte Subsets/immunology/metabolism ; },
abstract = {Post-treatment Lyme Disease (PTLD) is a poorly understood complication of Borrelia burgdorferi infection with significant patient morbidity. Characterized by fatigue, generalized myalgias, and cognitive impairment, PTLD symptomatology closely resembles long COVID and other post-acute infection syndromes. While prior studies suggest immune dysregulation as a factor in PTLD pathogenesis, the mechanisms underlying its heterogeneous presentation and severity remain unclear. To associate symptom burden with discrete immune phenotypes, we applied factor analysis to self-reported symptom data from 272 PTLD patients to generate patient subgroups. We then immunophenotyped peripheral blood cells of these individuals and 28 healthy controls through 19-parameter flow cytometry and cytokine profiling to associate PTLD status and the newly defined subgroups with specific immune states. Our PTLD cohort had fewer circulating CXCR5+ CD4+ naïve T cells relative to healthy controls (5.2% vs. 8.3%, Padj < 0.001). These cells were positively associated with musculoskeletal pain in PTLD participants, but not healthy controls. This and additional immunophenotypic alterations, including an increased prevalence of CXCR3+ CCR4- CCR6- CD8 T cells (43.1% vs. 25.7%, Padj < 0.01), permitted the creation of an elastic net classifier which identified PTLD with moderate efficacy (AUC 0.83). Measurement of cytokines did not reveal associations with PTLD and did not improve the performance of the model. While we could not identify immune features which distinguished all patient subgroups, we did observe a female-specific increase in central memory CD8 T cells restricted to one high-fatigue patient subgroup. Additionally, factor analysis revealed multiple associations between immune cell frequency and the severity of specific symptoms. Collectively, our findings add to growing evidence of immune dysfunction as a prominent feature of PTLD.},
}
@article {pmid40703169,
year = {2025},
author = {Vu, TT and Hua, MJ and Dubois, C and Moskowitz, JT and Wallia, A and Hirschhorn, LR and Wilkins, JT and Evans, CT},
title = {Long COVID and its associations with burnout, anxiety, and depression among U. S. healthcare workers in the United States.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1582872},
pmid = {40703169},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Health Personnel/psychology/statistics &amp; numerical data ; Male ; Female ; Adult ; *Anxiety/epidemiology ; *Burnout, Professional/epidemiology ; Cross-Sectional Studies ; *Depression/epidemiology ; Middle Aged ; United States/epidemiology ; Longitudinal Studies ; Surveys and Questionnaires ; SARS-CoV-2 ; Chicago/epidemiology ; },
abstract = {BACKGROUND: Data on Long COVID and its associations with burnout, anxiety and depression among healthcare workers (HCW) in the United States (U. S.) is limited.<br><br>METHODS: This study utilized cross-sectional data from the final survey conducted in July 2023, which was part of a longitudinal cohort study assessing COVID-19-related burnout and wellbeing among healthcare workers (HCWs) in a large tertiary academic healthcare system in the Chicago area. The survey included questions on self-reported Long COVID status, as well as the Oldenburg Burnout Inventory (OLBI) to measure burnout and the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CAT) to assess anxiety and depression. A total of 1,979 HCWs participated in the survey, yielding a response rate of 56.1%.<br><br>RESULTS: The analysis included 1,678 respondents with complete data, of whom 1,171 (70%) self-reported having had COVID-19. Of these, 90 (7.7%) reported Long COVID, with 53% indicating that their most bothersome symptoms persisted for more than 6&#x202f;months, while 50% reported no longer experiencing those symptoms at the time of the survey. Multivariable linear regression analyses revealed that Long COVID was significantly associated with higher OLBI scores (&#x3b2;&#x202f;=&#x202f;2.20, p&#x202f;=&#x202f;0.004), PROMIS anxiety scores (&#x3b2;&#x202f;=&#x202f;2.64, p&#x202f;=&#x202f;0.001) and PROMIS depression scores (&#x3b2;&#x202f;=&#x202f;1.98, p&#x202f;=&#x202f;0.011) compared to those who had COVID-19 but not Long COVID. Similar patterns of associations were observed when comparing the Long COVID group to those who never had COVID-19. No significant differences were found between those who never had COVID-19 and those who had COVID-19 without developing Long COVID.<br><br>CONCLUSION: Long COVID was associated with higher levels of burnout, depression, and anxiety among healthcare workers compared to those who had COVID-19 alone or were never infected, despite its lower prevalence during the endemic phase. These findings underscore the need for continued prevention efforts and targeted support strategies in healthcare settings.},
}
@article {pmid40702518,
year = {2025},
author = {Hadidchi, R and Patel, B and Madan, J and Liu, A and Henry, S and Duong, TQ},
title = {Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {815},
pmid = {40702518},
issn = {1479-5876},
mesh = {Humans ; *Fatigue Syndrome, Chronic/epidemiology/etiology ; *COVID-19/complications/epidemiology ; Female ; Male ; Middle Aged ; Retrospective Studies ; Adult ; *SARS-CoV-2 ; Risk Factors ; Incidence ; Aged ; Biomarkers/blood ; },
abstract = {BACKGROUND: Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for SARS-CoV-2, re-infection, and blood biomarkers at time of infection remain unclear. This study investigated the incidence and independent predictors of developing new-onset CFS/ME up to 4 years post SARS-CoV-2 infection in comparison to COVID- controls.<br><br>METHODS: This retrospective analysis conducted within the Montefiore Health System from February 1, 2020, to January 12, 2024 included adults without a prior diagnosis of fatigue or CFS/ME who were hospitalized for COVID-19 (n&#x2009;=&#x2009;10,667), not hospitalized for COVID-19 (n&#x2009;=&#x2009;25,409), and non-COVID-19 controls (n&#x2009;=&#x2009;111,301). The observation time was between 30&#xa0;days and 4&#xa0;years post index date. The outcome was new-onset CFS/ME. Multivariate adjusted hazard ratios (HR) with 95% confidence intervals were calculated, assessing risk posed by SARS-CoV-2 infection, re-infection, and vaccination. Whether abnormal levels of aspartate aminotransferase, creatinine, D-dimer, lactate dehydrogenase, ferritin, hemoglobin, platelets, neutrophil/lymphocyte ratio, and temperature during hospitalization were associated with future CFS/ME risk was examined.<br><br>RESULTS: Compared to COVID-&#x2009;controls, the risk of developing new-onset CFS/ME was higher among both COVID-19 hospitalized (adjusted HR&#x2009;=&#x2009;1.46 [1.07, 1.99]) and non-hospitalized patients (1.56 [1.25, 1.93]). Females (1.54 [1.27, 1.89]), patients with liver disease (1.61 [1.29, 2.00]), autoimmune disorders (1.57 [1.18, 2.08]), and anxiety disorders (1.35 [1.04, 1.74]) were more likely to develop CFS/ME (p&#x2009;<&#x2009;0.05). Re-infection with SARS-CoV-2 was not associated with increased risk of incident CFS/ME. COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p&#x2009;<&#x2009;0.05). None of the blood biomarkers during acute COVID-19 were associated with new-onset CFS/ME risk (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: SARS-CoV-2 infection is associated with an increased risk of new-onset CFS/ME, independent of hospitalization status. Females, and individuals with autoimmune and anxiety disorders were more susceptible. These findings highlight the need for ongoing surveillance and management of fatigue-related symptoms in COVID-19 survivors.},
}
@article {pmid40700379,
year = {2025},
author = {Gottlieb, M and Spatz, ES and Yu, H and Ebna Mannan, I and Santangelo, M and Malicki, C and Gentile, NL and Geyer, RE and Charlton, A and Dyal, JW and Elmore, JG and Gatling, K and Hill, MJ and Montoy, JCC and O'Laughlin, KN and Rising, KL and Saydah, S and Stephens, KA and Wang, RC and Wisk, LE and Venkatesh, AK and Weinstein, RA and , },
title = {Effects of long COVID on healthcare utilization.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0327218},
pmid = {40700379},
issn = {1932-6203},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/epidemiology ; Emergency Service, Hospital/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data ; Longitudinal Studies ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Prospective Studies ; SARS-CoV-2/isolation &amp; purification ; Telemedicine ; United States/epidemiology ; Secondary Data Analysis ; },
abstract = {BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC.<br><br>METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the 6 months following enrollment. Consistent with prior work, LC was defined as &#x2265;3 post-infectious symptoms at 3 months, while those with <3 symptoms were categorized as not having LC. Our primary outcome was to compare the change in visit types between pre- and post-index testing (hospitalization, emergency department visit, office visit, procedure, telehealth, and other). As secondary outcomes, we assessed differences in visit complexity using the summative length of each encounter for each category as a measure of total healthcare usage.<br><br>RESULTS: A total of 847 participants met inclusion criteria (179 LC, 668 non-LC). When compared with the pre-index period, there was an overall increase in visit numbers of all six visit categories during the post-index period for all groups, most pronounced in office and telehealth visits. When compared with the non-LC group, the LC group was less likely to have ED visits (OR: 0.1; 95% CI 0.0-0.5). However, among those with LC who had at least one hospitalization, they were more likely to have additional hospitalizations (OR: 2.6; 95% CI 1.5-4.6). Visit length for office visits and hospitalization in the LC group was increased when compared with the non-LC group, though this diminished after adjustment for patient baseline characteristics.<br><br>CONCLUSIONS: All participants who were infected with SARS-CoV-2 had a marked increase in healthcare utilization during the subsequent 180 days. The LC group had significantly higher rates of additional hospitalization compared with those without LC, which may help to inform healthcare resource planning.},
}
@article {pmid40700078,
year = {2025},
author = {Kuliyeva, A and Serejnikova, N and Eshmotova, G and Teslya, Y and Ivina, A and Zarov, A and Panin, M and Prizov, A and Lyalina, V and Shestakov, D and Fayzullin, A and Timashev, P and Volkov, A},
title = {Post-COVID-19 Femoral Head Osteonecrosis Exhibits Mast Cell Clusters, Fibrosis, and Vascular Thrombosis: Key Pathological Mechanisms in Long COVID-19 Bone Degeneration.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {32},
number = {3},
pages = {},
pmid = {40700078},
issn = {1873-149X},
support = {075-15-2024-658//the Ministry of Science and Higher Education of the Russian Federation/ ; },
abstract = {Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a common condition in hip surgery, which is characterized by the death of bone cells due to disruption of the blood supply and ultimately irreversible destruction of the hip joint. As a result of the COVID-19 pandemic, a significant increase in the incidence of ONFH has been identified. To better understand the pathogenesis of ONFH in the context of COVID-19, our research aimed to determine pathomorphological changes in articular tissues specific to post-COVID-19 ONFH. Methods: Using morphological, morphometric, and statistical methods, the femoral heads after hip arthroplasty were retrospectively studied in patients with post-COVID-19 ONFH (n = 41) compared to a non-COVID-19 group of patients (n = 47). Results: Our results revealed that the key morphofunctional biomarkers of post-COVID-19 ONFH were clusters of mast cells, extensive areas of fibrosis, numerous arterial and venous thrombi, and giant cell granulomas. The potential relationship of those morphological features with the action of the SARS-CoV-2 coronavirus was discussed. Conclusions: Mast cells have been proposed as the leading players that may trigger the main molecular and cellular mechanisms in the development of post-COVID-19 ONFH and can be considered a diagnostic sign of the disease.},
}
@article {pmid40699644,
year = {2025},
author = {Korobova, ZR and Arsentieva, NA and Liubimova, NE and Batsunov, OK and Butenko, AA and Kokoeva, AE and Kucherenko, NG and Kashchenko, VA and Boeva, EV and Norka, AO and Knizhnikova, AA and Rassokhin, VV and Belyakov, NA and Totolian, AA},
title = {B Cell Dynamics and Transitional B Cells in Long COVID.},
journal = {Current issues in molecular biology},
volume = {47},
number = {4},
pages = {},
pmid = {40699644},
issn = {1467-3045},
support = {121030200299-3//Federal Service on Customers' Rights Protection and Human Well-Being Surveillance of Russia/ ; },
abstract = {BACKGROUND: Long COVID is characterized by persistent symptoms following acute SARS-CoV-2 infection. This study aims to evaluate immune system markers, including antigen-specific antibodies, B cell subsets, and Th2-related cytokines, in individuals with long COVID and to investigate their potential impact on the development of this condition.<br><br>METHODS: We analyzed blood plasma from 63 individuals diagnosed with long COVID based on clinical presentation and 47 healthy individuals with COVID-19 history but no clinical symptoms. Antigen-specific IgG antibodies were measured using commercial ELISA kits. Lymphocyte subpopulations were assessed via flow cytometry and a gating strategy based on CD27 and CD38. Th2 cytokines (IL-4, IL-5, IL-13) were quantified using the xMAP multiplex assay.<br><br>RESULTS: We noted no significant differences in IgG levels between groups. Notably, individuals with long COVID demonstrated a higher percentage of naive mature B cells (CD27-CD38+), while transitional (CD27-CD38+++) and double-negative (DN, CD27-CD38-) cells were significantly reduced. Elevated levels of IL-5 and IL-13 were observed in long COVID patients. Classification analysis revealed that the percentage of transitional B cells (CD27-CD38+++) was a strong predictor of long COVID.<br><br>CONCLUSIONS: Our findings highlight alterations in B cell dynamics among individuals with long COVID, which may contribute to autoimmune processes.},
}
@article {pmid40697636,
year = {2025},
author = {Welbel, R and Rutha, E and Ording, J and Wang, D and Hirschtick, J},
title = {The Effects of a Mindfulness-Based Intervention on Depression and Anxiety in the Long-COVID Population.},
journal = {Journal of patient-centered research and reviews},
volume = {12},
number = {3},
pages = {134-139},
pmid = {40697636},
issn = {2330-0698},
abstract = {Long-COVID is a complicated, post-viral syndrome involving multiple body systems and can present with neuropsychiatric symptoms. Little has been reported about the neuropsychiatric symptoms of long-COVID, and validated treatments do not yet exist. There is prior evidence that mindfulness-based strategies have been helpful for those with chronic illnesses; shown significant decreases in anxiety, stress, and depression; and enhanced quality of life. In this study, we report on the utility of a mindfulness-based intervention on levels of anxiety and depression in a long-COVID population. Our hospital system founded both a "Covid Recovery Clinic" (CRC) and a "Post-COVID Resilience Program" (PCRP). The PCRP consisted of a six-week virtual group therapy protocol that focused on mindfulness-based practices. Before and after the therapy intervention, participants answered questionnaires to capture depressive and anxiety symptoms. Pre- and post-questionnaire scores do not show a significant improvement in depressive or anxiety symptoms, although the study was limited by a small sample size. Further research is needed to investigate whether similar programs with a larger sample size can improve the mental health status of patients suffering from long-COVID.},
}
@article {pmid40696830,
year = {2025},
author = {Paulose, M and Adams, NN and Martin, KR and Grant, A},
title = {Lived Experiences of New-Onset Long Covid Pain and Its Impact on Health-Related Quality of Life. A Scoping Review of Current Evidence.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70352},
pmid = {40696830},
issn = {1369-7625},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/complications/psychology ; *Chronic Pain/psychology/etiology ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long Covid (LC) is a multisystem condition that can cause persistent symptoms such as breathlessness, fatigue, cognitive problems and pain, with major effects on individuals and healthcare systems. Globally, nearly 400 million people have been affected. New-onset pain is among the most commonly reported symptoms and may develop into chronic pain, contributing to reduced health-related quality of life (HRQoL) and highlighting the need for appropriate care. Given its global prevalence, exploring how people experience new-onset LC pain and how it impacts their lives can help improve pain management and support services.<br><br>METHODS: A mixed-methods scoping review was conducted following the Joanna Briggs Institute (JBI) guidance and the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews (PRISMA-ScR). The review mapped and synthesised evidence from eligible primary research articles (quantitative, qualitative and mixed-methods) published in English between December 2019 and June 2024. Seven studies using cross-sectional, case-control and observational designs (n&#x2009;=&#x2009;30 to 2507 participants) were included, with data collected from Europe and Asia.<br><br>RESULTS: While qualitative data on lived experience were limited, 69.5% of LC patients reported new-onset pain, most commonly musculoskeletal (MSK) pain (73.2%). Psychological symptoms such as post-traumatic stress disorder (PTSD) were also reported (38%). Pain medications were widely used. Findings suggest that new-onset LC pain affects physical, psychological and social well-being. No studies involving children or adolescents were identified, indicating a gap in the evidence on paediatric experiences of new-onset LC pain.<br><br>CONCLUSION: This review highlights major gaps in the literature, especially the lack of qualitative research on how people experience new-onset LC pain. Future research should explore these experiences in depth, with involvement from patients and the public, to inform the development of appropriate treatment and support strategies.<br><br>During the review process, opportunities to involve PPI were not fully explored due to limited awareness of how to support meaningful involvement in a scoping review, alongside time and resource constraints. Such involvement could have helped shape the review question, refine the search terms and interpret the findings in ways that better reflect lived experience. This is acknowledged as both a limitation and a learning point. PPI will be actively embedded in the next phases of the research.},
}
@article {pmid40696212,
year = {2025},
author = {Harsányi, L and Kincses, Z and Veselinović, M and Zehetner, J and Altorjay, &#xc1;},
title = {Five-year clinical outcomes of RefluxStop surgery in the treatment of acid reflux: a prospective multicenter trial of safety and effectiveness.},
journal = {Surgical endoscopy},
volume = {39},
number = {9},
pages = {6163-6179},
pmid = {40696212},
issn = {1432-2218},
mesh = {Humans ; *Gastroesophageal Reflux/surgery ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; Treatment Outcome ; Aged ; Esophageal pH Monitoring ; Follow-Up Studies ; Quality of Life ; },
abstract = {INTRODUCTION: RefluxStop surgery corrects all three components of the anti-reflux barrier without affecting the food passageway. Long-term 5-year safety and effectiveness clinical outcomes are presented from the RefluxStop CE mark trial, used in an FDA PMA submission. This comprehensive and meticulously controlled data are, therefore, presented across multiple reports with other outcomes in a separate complementary article.<br><br>METHODS: A prospective, single-arm, multicenter clinical study was conducted to investigate RefluxStop surgery in 50 adults with chronic GERD, PPI use, GERD-HRQL score, 24-h pH testing, contrast-swallow x-ray, and serious/non-serious AEs presented.<br><br>RESULTS: Forty-four (n&#x2009;=&#x2009;44) subjects completed 5-year follow-up, whereof 91% underwent pH testing and contrast-swallow x-ray. Three subjects were withdrawn due to COVID-19 (two deaths and one long-COVID), all well-treated beforehand, at 3-4&#xa0;years. PPI usage (including COVID-19 subjects) in 1/47 (2.1%). The median (IQR) total GERD-HRQL score improved by 90% (72-98%) from a baseline of 29.5 (33.0-24.0) to 3.0 (0.5-7.5) at 5&#xa0;years (p&#x2009;<&#x2009;0.001) and 24-h pH monitoring results improved by 90.4% to a mean total acid exposure time (pH&#x2009;<&#x2009;4) of 1.57% from 16.35% at baseline (p&#x2009;<&#x2009;0.001). No cases (0%) of device explantation, migration/erosion, or esophageal dilatation occurred during the study. Five-year contrast-swallow x-ray showed zero (0%) dislocations, migrations, or re-herniations. Five subjects (n&#x2009;=&#x2009;5) experienced serious AEs of which all were resolved. Only two procedure-related AEs occurred between 1 and 5&#xa0;years, one moderate dyspepsia and one mild dysphagia, subsequently resolved.<br><br>CONCLUSION: The RefluxStop procedure demonstrated exceptional long-term 5-year outcomes. Only one subject took PPIs at follow-up. Both median GERD-HRQL scores and mean 24-h pH results improved by&#x2009;>&#x2009;90% from baseline (p&#x2009;=&#x2009;0.001). No device-related AEs, explantations, or migrations occurred during the 5-year study. Only two procedure-related AEs occurred between 1 and 5&#xa0;years, one dyspepsia and one mild dysphagia (resolved). These objective and patient-reported results were robustly maintained from previously published 1- to 4-year data.},
}
@article {pmid40695836,
year = {2025},
author = {Coleon, A and Larrous, F and Kergoat, L and Tichit, M and Hardy, D and Obadia, T and Kornobis, E and Bourhy, H and de Melo, GD},
title = {Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6714},
pmid = {40695836},
issn = {2041-1723},
support = {ANRS MIE 202112015304//Fondation pour la Recherche M&#xe9;dicale (Foundation for Medical Research in France)/ ; PFR-4 - Long Covid//Institut Pasteur/ ; 2022-2023 Brain Axis SRA3 M2 Master Student Call//Institut Pasteur/ ; },
mesh = {Animals ; *COVID-19/genetics/virology/metabolism/pathology/complications/immunology ; *SARS-CoV-2/physiology/genetics ; Mesocricetus ; *Transcriptome ; *Brain Stem/virology/metabolism/pathology ; Cricetinae ; Disease Models, Animal ; Male ; Anxiety ; Humans ; Immunity, Innate/genetics ; *Neurodegenerative Diseases/genetics/virology ; Depression ; RNA, Viral ; },
abstract = {Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood. Using golden hamsters as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persistently infect the brain, as viral RNA and replicative virus are detected in the brainstem 80 days after the initial infection. Infected hamsters exhibit a neurodegenerative signature in the brainstem, characterized by overexpression of innate immunity genes, and altered expression of genes involved in the dopaminergic and glutamatergic synapses, in energy metabolism, and in proteostasis. These infected animals exhibit persistent depression-like behavior, impaired short-term memory, and late-onset signs of anxiety. Finally, we provide evidence that viral and immunometabolic mechanisms coexist in the brainstem of SARS-CoV-2-infected hamsters, contributing to the manifestation of neuropsychiatric and cognitive symptoms.},
}
@article {pmid40694553,
year = {2025},
author = {Ma, KPK and Stober, T and Gottlieb, M and Geyer, RE and Rising, K and Saydah, S and Santangelo, M and Gatling, K and Grau, D and Wang, RC and Montoy, JC and Idris, A and MacDonald, S and Hill, MJ and Huebinger, R and Prado, MG and Gentile, NL and Spatz, E and Maliki, C and Dorney, J and Elmore, JG and L'Hommedieu, M and Weinstein, RA and Venkatesh, AK and Stephens, KA and , },
title = {Participant engagement in a national longitudinal study of COVID-19: Insights from the INSPIRE study.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0325948},
pmid = {40694553},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology/virology ; Longitudinal Studies ; Male ; Female ; Middle Aged ; Adult ; Motivation ; United States/epidemiology ; Surveys and Questionnaires ; SARS-CoV-2/isolation &amp; purification ; Aged ; *Patient Participation/psychology ; Registries ; },
abstract = {OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.<br><br>METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.<br><br>RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings.<br><br>CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research.<br><br>POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.},
}
@article {pmid40694308,
year = {2025},
author = {Floridia, M and Weimer, LE and Rovere Querini, P and Bonfanti, P and Lacedonia, D and Figliozzi, S and Zucco, S and Andreozzi, P and Barisione, E and Lo Forte, A and Gnerre, P and Loso, K and Onder, G and , },
title = {Persistence of symptoms in long-COVID: follow-up trajectories of 30 symptoms in 755 patients from a national multicenter study from Italy.},
journal = {Internal and emergency medicine},
volume = {20},
number = {7},
pages = {2041-2055},
pmid = {40694308},
issn = {1970-9366},
support = {I85F21003410005//Ministero della Salute/ ; },
mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/complications/physiopathology/diagnosis ; Italy/epidemiology ; Middle Aged ; Aged ; Adult ; Follow-Up Studies ; SARS-CoV-2 ; Risk Factors ; },
abstract = {Aim of the study was to define the patterns and determinants of symptom persistence in Long-COVID. The study population was represented by a multicenter cohort of patients with persisting symptoms after SARS-CoV-2 infection. Data collection included demographics, comorbidities, characteristics of acute infection, vaccination, reinfection, plus 30 different symptoms. The associations between covariates and persistence were assessed in multivariable logistic regression models. The study evaluated, at a mean interval of 453 days from acute SARS-CoV-2 infection, symptom persistence in 755 patients who had Long-COVID symptoms at a mean interval of 223 days from COVID-19. At second evaluation, 423 (56.0%) patients still presented one or more symptoms and 332 (44.0%) were symptom free. In those who remained symptomatic, the mean number of symptoms significantly reduced between the two evaluations. Compared to the first evaluation, the overall mean symptom regression rate was 72%, with lower regression rates observed for dyspnea (53%), anxiety (54%) and sleep disturbances (55%). The risk of persistence was increased for female sex, higher BMI, hospitalization and stronger ventilatory support during acute disease, higher number of initial symptoms and particular comorbidities (anxiety, chronic pulmonary disease, asthma), and decreased with the increase of age and time from acute SARS-CoV-2 infection. Neither SARS-CoV-2 vaccination nor reinfection showed significant associations with persistence. In this case series, roughly half of the patients that were symptomatic 7 months after acute SARS-CoV-2 infection remained symptomatic after an additional 7 months. The pattern and predictors of persistence draw attention to certain particular risk factors and manifestations that tend to persist longer than others.},
}
@article {pmid40693778,
year = {2025},
author = {Song, Y and Mehl, F and Muehling, LM and Canderan, G and Enfield, K and Sun, J and Yin, MT and Ratcliffe, SJ and Wilson, JM and Kadl, A and Woodfolk, JA and Zeichner, SL},
title = {ACE-2-like enzymatic activity in COVID-19 convalescents with persistent pulmonary symptoms associated with immunoglobulin.},
journal = {mBio},
volume = {16},
number = {8},
pages = {e0173525},
pmid = {40693778},
issn = {2150-7511},
support = {//Ivy Foundation/ ; AI176515//National Institute of Allergy and Infectious Diseases/ ; //The Pendleton Laboratory Fund for Pediatric Infectious Diseases/ ; R01 AI176515/AI/NIAID NIH HHS/United States ; AI160334//National Institute of Allergy and Infectious Diseases/ ; //Manning Fund for COVID-19 Research at UVVA/ ; AI178669//Alpha-1 Foundation/ ; R56 AI178669/AI/NIAID NIH HHS/United States ; R21 AI160334/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/immunology ; SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Male ; Female ; *Antibodies, Viral/immunology/blood ; Middle Aged ; *Peptidyl-Dipeptidase A/metabolism/immunology ; Pandemics ; *Pneumonia, Viral/immunology ; Adult ; *Coronavirus Infections/immunology ; *Betacoronavirus/immunology ; Aged ; *Antibodies, Catalytic/immunology ; Convalescence ; },
abstract = {UNLABELLED: Many difficult-to-understand clinical features characterize COVID-19 and post-acute sequelae of COVID-19 (PASC or long COVID [LC]). These can include blood pressure instability, hyperinflammation, coagulopathies, and neuropsychiatric complaints. The pathogenesis of these features remains unclear. The SARS-CoV-2 Spike protein receptor-binding domain (RBD) binds angiotensin converting enzyme 2 (ACE2) on the surface of host cells to initiate infection. We hypothesized that some people convalescing from COVID-19 may produce anti-RBD antibodies that resemble ACE2 sufficiently to have ACE2-like catalytic activity, that is, they are ACE2-like proteolytic abzymes that may help mediate the pathogenesis of COVID-19 and LC. In previous work, we showed that some people with acute COVID-19 had immunoglobulin-associated ACE2-like proteolytic activity, suggesting that some people with COVID-19 indeed produced ACE2-like abzymes. However, it remained unknown whether ACE2-like abzymes were seen only in acute COVID-19 or whether ACE2-like abzymes could also be identified in people convalescing from COVID-19. Here, we show that some people convalescing from COVID-19 attending a clinic for people with persistent pulmonary symptoms also have ACE2-like abzymes and that the presence of ACE2-like catalytic activity correlates with alterations in blood pressure in an exercise test.<br><br>IMPORTANCE: Patients who have had COVID-19 can sometimes have troublesome symptoms, termed post-acute sequelae of COVID-19 (PASC) or long COVID (LC), which can include problems with blood pressure regulation, gastrointestinal problems, inflammation, blood clotting, and symptoms like "brain fog." The proximate causes for these problems are not known, which makes these problems difficult to treat definitively. We previously found that some acute COVID-19 patients make antibodies against SARS-CoV-2, the virus that causes COVID-19, that act like an enzyme, angiotensin converting enzyme 2 (ACE2). ACE2 normally helps regulate blood pressure and serves as the receptor for SARS-CoV-2 in the body. We show that patients convalescing from COVID-19 also make antibodies that act like ACE2 and that the presence of those antibodies correlates with problems in blood pressure regulation. The findings provide a new opening to potentially understanding the causes of LC, and so provide direction for the development of new treatments.},
}
@article {pmid40690153,
year = {2025},
author = {Abbasi, A and Sharma, R and Hansen, N and Pirrotte, P and Stringer, WW},
title = {Possible long COVID biomarker: identification of SARS-CoV-2 related protein(s) in Serum Extracellular Vesicles.},
journal = {Infection},
volume = {53},
number = {6},
pages = {2909-2912},
pmid = {40690153},
issn = {1439-0973},
}
@article {pmid40687082,
year = {2025},
author = {Motokawa, Y and Sugihara, J and Tateishi, T and Hosoya, T and Yasuda, S and Miyazaki, Y and Takahashi, H and Shiwaku, H},
title = {Long COVID is associated with female sex; Anti-NCAM1 autoantibodies are absent in patients with long COVID.},
journal = {IBRO neuroscience reports},
volume = {19},
number = {},
pages = {252-256},
pmid = {40687082},
issn = {2667-2421},
abstract = {BACKGROUND: Long COVID is a condition that may arise following SARS-CoV-2 infection and is associated with a range of systemic complications. Autoantibodies are implicated in the pathogenesis of long COVID. However, the details of the pathogenic mechanisms undergone by these autoantibodies remain unclear. Neural cell adhesion molecule 1 (NCAM1) is the human protein with the highest sequence homology to the SARS-CoV-2 proteins. Previous in silico studies indicate that SARS-CoV-2 infection may induce the production of anti-NCAM1 autoantibodies. Thus, this study investigated the presence of anti-NCAM1 autoantibodies in individuals affected by COVID-19, including those with long COVID.<br><br>METHODS: Serum samples were obtained from 173 individuals 3 months after SARS-CoV-2 infection. Among them, 63 were diagnosed with long COVID. A cell-based assay was used to assess all 173 serum samples for the presence of anti-NCAM1 autoantibodies. We also analyzed the clinical profiles of patients with and without long COVID to identify potential risk factors associated with long COVID.<br><br>RESULTS: Anti-NCAM1 autoantibodies were not detected in any serum sample. The proportion of female patients in the long COVID group was significantly higher than that in the non-long COVID group.<br><br>CONCLUSION: The results indicate that the production of anti-NCAM1 autoantibodies following COVID-19 is unlikely. Female sex is associated with higher risk of long COVID.},
}
@article {pmid40685660,
year = {2025},
author = {Davis, S and Mon-Yee, M and Sutton, A and Leaviss, J and Forsyth, JE and Burton, C},
title = {Cost effectiveness of non-pharmacological interventions for fatigue in patients with long-term conditions: a systematic literature review.},
journal = {Expert review of pharmacoeconomics &amp; outcomes research},
volume = {25},
number = {8},
pages = {1159-1166},
doi = {10.1080/14737167.2025.2537194},
pmid = {40685660},
issn = {1744-8379},
mesh = {Humans ; Cost-Benefit Analysis ; *Cognitive Behavioral Therapy/economics/methods ; *Fatigue/therapy/economics/etiology ; Chronic Disease ; *Exercise Therapy/economics/methods ; United Kingdom ; Cost-Effectiveness Analysis ; },
abstract = {INTRODUCTION: We aimed to assess the cost-effectiveness of non-pharmacological interventions for fatigue in patients with chronic conditions in the UK.<br><br>METHODS: This systematic review of cost-effectiveness studies aligns with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. Data sources: Electronic databases and citation searches. Inclusion criteria: Studies including adults with one or more long-term health condition, either physical or mental. Exclusion criteria: Studies associated with cancer, long-COVID, post-viral fatigue, medically unexplained conditions, developmental disorders and injuries. Assessment: A single reviewer completed a two-stage sifting process.<br><br>RESULTS: Four studies met the inclusion criteria. They included patients with either multiple sclerosis or inflammatory rheumatic conditions, and assessed either cognitive behavioral therapy (CBT) or a personalized exercise program (PEP). CBT was either dominated by usual care or had an incremental cost-effectiveness ratio (ICER) over &#xa3;30,000. PEP dominated CBT, with the ICER for PEP versus usual care ranging from &#xa3;13,159 to &#xa3;35,424.<br><br>CONCLUSIONS: The economic literature on this topic is much more limited than the clinical effectiveness literature, both in terms of interventions and populations covered. Future research should focus on a de novo economic evaluation to identify interventions with a high potential to be cost-effective across multiple conditions.<br><br>REGISTRATION: PROSPERO (CRD42023440141).},
}
@article {pmid40684905,
year = {2025},
author = {Gershon, AS and Fung, D and Lam, GY},
title = {Diagnosing Respiratory Long COVID: A Practical Approach.},
journal = {Chest},
volume = {168},
number = {4},
pages = {874-879},
pmid = {40684905},
issn = {1931-3543},
mesh = {Humans ; *COVID-19/complications/diagnosis/physiopathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Dyspnea/etiology ; Cough/etiology ; Male ; Fatigue/etiology ; Middle Aged ; Female ; },
abstract = {Long COVID or a post-COVID condition, defined as the persistence of symptoms at least 3 months after acute COVID-19 infection, is a novel condition in which a definitive diagnostic marker and treatment have yet to be found. This condition, which has been estimated to impact > 65 million individuals worldwide, manifests with multisystem involvement, most commonly presenting with fatigue, brain fog, dyspnea, cough, or a combination thereof. The burden of these symptoms can range from mild to severe, with many patients reporting an inability to return to usual activities. Herein, we present several hypothetical but clinically representative case reports to allow discussion around how we approach the diagnosis of respiratory symptoms of long COVID in those with and without chronic lung disease.},
}
@article {pmid40684788,
year = {2025},
author = {Kirby, T},
title = {Joan B Soriano-expert on asthma, COPD, and long COVID.},
journal = {The Lancet. Respiratory medicine},
volume = {13},
number = {8},
pages = {672-673},
doi = {10.1016/S2213-2600(25)00253-X},
pmid = {40684788},
issn = {2213-2619},
}
@article {pmid40684361,
year = {2026},
author = {Baldassarre, G and Zuccarelli, L and Favaretto, T and Ursella, C and Palomba, A and Salvador, PCDN and Sozio, E and Crisafulli, E and Imazio, M and Tascini, C and Grassi, B},
title = {Persistence of fatigue in the absence of pathophysiological mechanisms in some patients more than 2 years after the original SARS-CoV-2 infection.},
journal = {Experimental physiology},
volume = {111},
number = {3},
pages = {1413-1428},
pmid = {40684361},
issn = {1469-445X},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Middle Aged ; Male ; Female ; *Fatigue/physiopathology/etiology ; Quality of Life ; SARS-CoV-2 ; Exercise Tolerance/physiology ; Aged ; Post-Acute COVID-19 Syndrome ; Exercise/physiology ; Dyspnea/physiopathology ; },
abstract = {Following an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a substantial percentage of patients report the persistence of debilitating symptoms, often grouped in a syndrome termed 'long COVID'. We sought to identify potential pathophysiological mechanisms responsible for the persistence, in some long COVID patients, of symptoms related to fatigue/exercise intolerance (excessive or early fatigue, excessive or early dyspnoea, muscle weakness, and myalgias) more than 2 years after the original infection. Twelve patients who reported persistent symptoms (Long COVID group; 57 ± 6 years, mean ± SD), and 14 patients without the symptoms (Control group; 57 ± 8 years) were evaluated. An extensive series of measurements were performed to identify pathophysiological mechanisms potentially responsible for the symptoms. In long COVID patients, all items evaluating quality of life (SF-36 questionnaire) had lower scores (P < 0.01) compared to control. The habitual level of physical activity, muscle size and strength, maximal aerobic power and the ventilatory thresholds, peak cardiac function, the mechanical efficiency of cycling, pulmonary V ̇ O 2 ${\dot V_{{{\mathrm{O}
}
_2}
}
}
$ kinetics, microvascular/endothelial function (hyperemic response in the common femoral artery during passive leg movements), skeletal muscle oxidative metabolism (peak fractional O2 extraction and muscle V ̇ O 2 ${\dot V_{{{\mathrm{O}
}
_2}
}
}
$ recovery kinetics by the repeated occlusions test, by near-infrared spectroscopy) were not different in the two groups. Evidence of ventilatory inefficiency was described in a subgroup of long COVID patients. More than 2 years after the original SARS-CoV-2 infection, a discrepancy was observed between the persistence of debilitating symptoms of fatigue/exercise intolerance and the absence of several investigated pathophysiological mechanisms. The discrepancy may be due to factors that remain to be elucidated.},
}
@article {pmid40683613,
year = {2025},
author = {Chen, K and Wang, Z and Li, J and Xu, Y and Gu, S and Li, H and Li, J and Zhang, Y and Mao, N},
title = {Chronic inflammation in Long COVID relationship to autoimmune diseases.},
journal = {Autoimmunity reviews},
volume = {24},
number = {10},
pages = {103882},
doi = {10.1016/j.autrev.2025.103882},
pmid = {40683613},
issn = {1873-0183},
mesh = {Humans ; *COVID-19/immunology/complications ; *Autoimmune Diseases/immunology/therapy/complications ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; Chronic Disease ; Gastrointestinal Microbiome/immunology ; Post-Acute COVID-19 Syndrome ; },
abstract = {The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.},
}
@article {pmid40682988,
year = {2025},
author = {Carvalho, LLM and Goulart, CDL and Pierazzo, GDD and Cordeiro-Costa, EL and Borghi-Silva, A and Garcia-Araújo, AS},
title = {Associations between lung and endothelial function in long COVID: Two years after acute infection.},
journal = {Heart &amp; lung : the journal of critical care},
volume = {74},
number = {},
pages = {168-173},
doi = {10.1016/j.hrtlng.2025.07.011},
pmid = {40682988},
issn = {1527-3288},
mesh = {Humans ; Female ; *COVID-19/physiopathology/complications ; Male ; Middle Aged ; Cross-Sectional Studies ; *Endothelium, Vascular/physiopathology ; SARS-CoV-2 ; *Lung/physiopathology ; Vasodilation/physiology ; Post-Acute COVID-19 Syndrome ; Respiratory Function Tests ; Brachial Artery/physiopathology ; Aged ; },
abstract = {BACKGROUND: endothelial cells may be a primary source for the initiation and spread of Acute Respiratory Distress Syndrome (ARDS) caused by SARS-CoV-2, resulting in severe endothelial injury and widespread thrombosis.<br><br>OBJECTIVE: The objective of this study was to evaluate the influence of lung function on the vascular response of patients with long COVID.<br><br>METHODS: This is an observational and cross-sectional study. Only one visit was performed, during which the evaluation form was completed and the post-COVID-19 Functional Status Scale (PCFS) was applied. In addition, participants underwent the assessment of flow-mediated vasodilation in the brachial artery and the assessment of pulmonary function.<br><br>RESULTS: A total of 32 participants were included, of which 19 (59 %) were women. The mean age was 55.8 &#xb1; 8.6 years, with a mean weight of 88.96 &#xb1; 21.66 kg. The participants had an average time of 32.25 months since the acute phase. The patients had an average of FEV&#x2081;/FVC 81.15&#xb1;14.7 (%) and KCO 93.72&#xb1;7.95 (%). FMD had an average of -0.21&#xb1;11.24 (%), indicating still impaired endothelial function. We found correlation between basal diameter (-0.21 [-4.26 to 3.84]) vs lung function variables, especially with the variable KCO (%) (p < 0.001; r = 0.560). When we perform simple linear regression KCO (%) indicates that this variable alone influences 29 % of the response to the basal diameter of the participants.<br><br>CONCLUSION: Two years after recovery from COVID-19 infection, the patients present changes in endothelial function, which have important implications for individuals when it comes to cardiovascular health.},
}
@article {pmid40680857,
year = {2025},
author = {Melkumyan, K and Simonyan, S and Shingala, D and Torossian, H and Mkrtumyan, K and Tulbenjyan, M and Hovhannisyan, Y and Yenkoyan, K},
title = {Three-year assessment of cognitive and olfactory disturbances among COVID-19 convalescent patients grouped by olfactory hallucination status in Armenia: A qualitative and quantitative study.},
journal = {Clinical medicine (London, England)},
volume = {25},
number = {5},
pages = {100489},
pmid = {40680857},
issn = {1473-4893},
mesh = {Humans ; *COVID-19/complications ; Male ; *Hallucinations/epidemiology/etiology ; Female ; Adult ; Middle Aged ; *Olfaction Disorders/epidemiology/etiology ; Aged ; Armenia/epidemiology ; SARS-CoV-2 ; Quality of Life ; Adolescent ; Young Adult ; Pandemics ; },
abstract = {BACKGROUND: Smell disturbances, memory and mood changes are frequently reported as symptoms of long COVID that can be debilitating and long-lasting, having a detrimental impact on a patient's quality of life and possibly contributing to depression and a decline in cognitive abilities.<br><br>STUDY OBJECTIVE: This study aims to investigate long-term post-COVID cognitive and olfactory disturbances among the COVID-19 convalescent adult Armenian population aged between 18 and 65 years. The assessment extends to the differentiation of various olfactory distortions and association between various olfactory and cognitive variables, grouped by participants' olfactory hallucination status.<br><br>STUDY DESIGN: Explanatory sequential mixed-methods design was employed. Through three follow-up visits, the quantitative phase evaluated olfactory and cognitive abnormalities following COVID-19, comparing those with and without olfactory hallucinations. Through in-depth interviews, the qualitative phase investigated how participants perceived these symptoms and their impact on their quality of life.<br><br>STUDY PARTICIPANTS: The quantitative study participants were those who self-reported subjective disturbances in the olfactory perception 14 days following a COVID-19 diagnosis, as confirmed by a positive PCR test at the time of diagnosis. The qualitative study participants were those who self-reported persistent olfactory disturbances post-visit 3.<br><br>RESULTS: The study found that olfactory hallucinations lead to more pronounced depression compared with non-hallucinogenic types of olfactory disturbances. It was determined that a significant predictor of parosmia is persistent anosmia up to 4 months following COVID-19 infection.<br><br>CONCLUSION: The long-term olfactory disturbances post-COVID-19 infection have a better prognosis among participants without olfactory hallucination compared to participants with olfactory hallucination.},
}
@article {pmid40680383,
year = {2025},
author = {Chen, TH and Jeng, TH and Lee, MY and Wang, HC and Tsai, KF and Chou, CK},
title = {Viral mitochondriopathy in COVID-19.},
journal = {Redox biology},
volume = {85},
number = {},
pages = {103766},
pmid = {40680383},
issn = {2213-2317},
mesh = {Humans ; *COVID-19/virology/metabolism/pathology/immunology/complications ; *SARS-CoV-2/pathogenicity ; *Mitochondria/metabolism/virology/pathology ; Mitochondrial Dynamics ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), disrupts cellular mitochondria, leading to widespread chronic inflammation and multi-organ dysfunction. Viral proteins cause mitochondrial bioenergetic collapse, disrupt mitochondrial dynamics, and impair ionic homeostasis, while avoiding antiviral defenses, including mitochondrial antiviral signaling. These changes drive both acute COVID-19 and its longer-term effects, known as "long COVID". This review examines new findings on the mechanisms by which SARS-CoV-2 affects mitochondria and for the impact on chronic immunity, long-term health risks, and potential treatments.},
}
@article {pmid40677535,
year = {2024},
author = {Mundra, P and Kailani, Z and Yaghoobi, M and Matthews, P and Tobis, M and Sadeghian, S and Albashir, S},
title = {Liver injury in post-acute COVID-19 syndrome: A systematic review and meta-analysis of early observational studies.},
journal = {Canadian liver journal},
volume = {7},
number = {4},
pages = {470-489},
pmid = {40677535},
issn = {2561-4444},
abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS; long COVID) is characterized by persistent or delayed symptoms at least 4 weeks from acute COVID-19 infection. Given the well-documented incidence of liver injury in acute COVID-19, this systematic review aims to assess the odds of liver injury in earlier experiencers of PACS.<br><br>METHODS: Observational studies published prior to March 2022 were screened for data describing liver injury (defined per primary study) in patients with PACS.<br><br>RESULTS: A total of 2,117 abstracts and 35 full texts were screened, of which 26 met the inclusion criteria. The mean time since acute COVID infection across all studies was 195.5 days. Seven studies included COVID-negative control groups. Twenty-three studies measured lab findings, and nine studies measured imaging or elastography. Five studies were eligible for meta-analysis of odds ratios, which did not demonstrate a statistically significant difference in odds for liver injury in patients with PACS compared with COVID-negative patients (OR 2.22 [95% CI 0.51-9.61; p = 0.28]). Newcastle-Ottawa Scale assessments for all studies found 24 of 26 studies with high to very high risk of bias. ROBINS-E assessments for studies included in the meta-analysis found five of five studies with high to very high risk of bias.<br><br>CONCLUSIONS: Overall, our findings demonstrate no statistical difference in odds ratios of liver injury in patients with PACS compared with COVID-negative controls. As such, routine assessment and monitoring of liver injury in patients with PACS may not be required; however, higher quality data with lower risk of bias are required to make recommendations of higher certainty.},
}
@article {pmid40676931,
year = {2025},
author = {Abdul-Azees, PA and Marinkovic, M and Singh, BB and Dean, DD and Chen, XD and Goldberg, MP and Restrepo, MI and Loomer, PM and Yeh, CK},
title = {The Impact of Aging Oral Health on Long COVID-19.},
journal = {Journal of dental research},
volume = {104},
number = {12},
pages = {1294-1303},
doi = {10.1177/00220345251349805},
pmid = {40676931},
issn = {1544-0591},
mesh = {Humans ; *COVID-19/complications/immunology ; *Oral Health ; *Aging/physiology/immunology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Mouth Diseases/virology ; },
abstract = {At least 10% of individuals infected with SARS-CoV-2 develop a variety of multisystem symptoms lasting more than 12 wk known as postacute sequelae of COVID-19 (PASC) or "long COVID." While the precise pathogenesis of PASC remains unclear, immune dysregulation is widely recognized as a key factor. Moreover, PASC disproportionately affects older individuals who are prone to age-related immune system decline, which further exacerbates the risk and severity of PASC. The oral cavity, a primary site for initial SARS-CoV-2 infection, may contribute to the development and persistence of PASC. Emerging evidence suggests that changes in age-related oral health, such as periodontitis, salivary gland (SG) dysfunction, and gustatory and olfactory impairments, may create an environment conducive to forming an oral reservoir of intact virus or viral antigens, which may contribute to the chronicity of PASC. Alternatively, the pathogenesis of PASC may increase the risk of a wide range of oral health issues, such as dental diseases, dry mouth, and sensory dysfunction (e.g., taste and smell) that are frequently reported by patients with PASC. This review highlights how aging facilitates oral SARS-CoV-2 infection, co-infection with other viruses may drive PASC in aging patients, aging and PASC dysregulate the oral microbiome, SARS-CoV-2 infection promotes molecular mechanisms involved in oral tissue aging, aging oral health affects susceptibility to developing PASC, and inflammation associated with PASC exacerbates dysregulation of metabolic/enzymatic pathways of aging oral mucosa and diseases of the periodontal apparatus, SGs, and taste. It underscores the urgent need to comprehensively address the interplay between aging oral health and PASC, which will help mitigate long-term complications and improve overall health outcomes for affected individuals.},
}
@article {pmid40672484,
year = {2025},
author = {Yadaw, AS and Sahner, DK and Sid, E and Chew, EY and Pichard, D and Mathé, EA},
title = {Impact of Preexisting Rare Diseases on COVID-19 Severity, Reinfection, and Long COVID, and the Modifying Effects of Vaccination and Antiviral Therapy: A Retrospective Study from the N3C Data Enclave.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40672484},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; 75N90023D00001/CL/CLC NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; 75N99023D00001/OF/ORFDO NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; 75N95021D00001/DA/NIDA NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; ZIC TR000410/ImNIH/Intramural NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; 75N94023D00001/HD/NICHD NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; 75N92023D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Over 10,000 rare diseases (RDs) affect more than 300 million people globally, yet their influence on COVID-19 severity, reinfection risk, and long COVID remains poorly understood. This study evaluates the impact of RDs on these outcomes and examines the effectiveness of vaccination and antiviral treatments among individuals with and without RDs.<br><br>METHODS: We conducted a retrospective cohort study using harmonized electronic health records (EHRs) from the National COVID Cohort Collaborative (N3C), encompassing 21,704,702 individuals, including 4,825,605 with confirmed SARS-CoV-2 infection between Jan 1, 2020, and Jan 4, 2024. RDs were defined using 12,003 conditions curated from GARD and Orphanet, mapped to OMOP concepts, and classified into 18 RD classes based on medical specialty involvement. Primary outcomes included: (1) COVID-19 severity (hospitalization and life-threatening disease), (2) long COVID, and (3) SARS-CoV-2 reinfection. We applied multivariable logistic regression with inverse probability of treatment weighting and reported adjusted odds ratios with 95% confidence intervals and associated p-values. Models were controlled for demographics, comorbidities, and exposure to vaccination and antiviral treatments.<br><br>FINDINGS: Of 21,704,702 individuals, we identify 4,825,605 COVID-19 positive individuals, 6.36% had RDs, with markedly higher rates of rare disease (RD) patients that have life-threatening illness (16% vs. 6.1% without life-threatening illness) and that are hospitalized (13% vs. 6.0% without hospitalization). Otorhinolaryngologic diseases showed the highest risk of life-threatening outcomes (OR 4.51; 95% CI 3.81-5.33), followed by developmental defect during embryogenesis (OR 1.84; 95% CI 1.72-1.98) and cardiac conditions (OR 1.79; 95% CI 1.51-2.11). Hospitalization risk was highest for otorhinolaryngologic (OR 2.90; 95% CI 2.61-3.23), developmental defect during embryogenesis (OR 2.06; 95% CI 1.97-2.16), and hematologic and endocrine diseases (OR 1.81; 95% CI 1.75-1.87 and OR 1.81; 95% CI 1.64-1.99, respectively).In patients with RDs, vaccination alone or antiviral treatment alone was associated with reduced odds of life-threatening COVID-19 disease compared to non-vaccinated individuals (OR 0.71; 95% CI 0.66-0.77 and OR 0.33; 95% CI 0.26-0.42, respectively). The combination of both vaccination and antiviral treatment showed the greatest reduction in odds ratio (OR 0.24; 95% CI 0.20-0.27). Similar results were observed in patients without RDs. In contrast, vaccination or antiviral therapy alone, compared to no intervention, did not significantly reduce long COVID risk in RD patients, although these interventions alone did result in a lower odds ratio in patients without RD. However, their combination was protective in both groups. Vaccination alone, compared to no vaccination, also reduced the risk of reinfection across RD and non-RD populations.<br><br>INTERPRETATION: RD patients face elevated risks of severe COVID-19 outcomes. While vaccination and antivirals significantly reduce the acute severity of illness, their impact on long COVID appears limited in this population. Notably, vaccination was protective against COVID-19 reinfection in both RD and non-RD populations. These findings highlight the need for targeted strategies to protect RD patients beyond current interventions, particularly in preventing long-term complications.},
}
@article {pmid40671933,
year = {2025},
author = {Zeballos, RS and da Silva Helbingen, MF and Melo, PMP and Alves, FEC and Salvino, CR and Seródio, EP and de Carvalho, ERM},
title = {Post spike syndrome (PSS): Simple solution leading to resolving results, five cases report.},
journal = {IDCases},
volume = {41},
number = {},
pages = {e02278},
pmid = {40671933},
issn = {2214-2509},
abstract = {UNLABELLED: Post-Spike Syndrome (PSS) is an emerging condition associated with the Spike protein, originating from both SARS-CoV-2 infection and mRNA-based therapies. This case series explores the significant clinical impact of PSS, characterized By gut dysbiosis, systemic inflammation, and immune activation, leading to multisystem manifestations such as fatigue, brain fog, neuropathies, and reactivation of pre-existing diseases. A simple therapeutic approach was applied to five patients, resulting in notable symptom improvement.<br><br>METHODS: This case series includes five patients diagnosed with interstitial granulomatous dermatitis, polymyalgia rheumatica, peripheral polyneuropathy, drug-refractory epilepsy, and trigeminal neuralgia. A common pathophysiological mechanism-vasculitis triggered by both SARS-CoV-2 and mRNA-based therapies-was hypothesised. The patients exhibited a satisfactory response to the proposed therapeutic strategy. This is an observational and descriptive study, with data collected retrospectively from medical records at a private clinic in S&#xe3;o Paulo, Brazil.<br><br>CONCLUSION: It is crucial to raise awareness within the medical community About SPIKEOPATHY, particularly in cases of classic pathologies that do not respond to conventional treatments. We believe PSS is currently underestimated. A broad intervention including a focus on restoring the microbiome, in particular Bifidobacterium associated with ivermectin and nattokinase was used as a therapeutic strategy. In other studies, Bifidobacterium has already been shown to significantly reduce harmful bact&#xe9;ria in post-COVID patients. Further studies are needed to confirm these findings and expand our understanding of PSS management.},
}
@article {pmid40671020,
year = {2025},
author = {Wang, Y and Li, X and Hui, H and Yang, D},
title = {Efficacy and safety of traditional Chinese medicine for post-COVID-19 syndrome: a systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {801},
pmid = {40671020},
issn = {1479-5876},
mesh = {Humans ; *Medicine, Chinese Traditional/methods/adverse effects ; *COVID-19/complications ; *Drugs, Chinese Herbal/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Treatment Outcome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue/drug therapy ; Cough/drug therapy ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Post-COVID-19 syndrome, characterized by persistent symptoms such as fatigue, dyspnea, cough, insomnia, and exercise intolerance, poses a significant challenge to global healthcare systems. Traditional Chinese Medicine (TCM) has been used to manage post-viral syndromes, but high-quality evidence for its effectiveness in post-COVID-19 recovery is limited. This study aimed to evaluate the clinical efficacy and safety of Chinese herbal medicine (CHM) in treating post-COVID-19 syndrome through a systematic review and meta-analysis of randomized controlled trials (RCTs).<br><br>METHODS: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Library and CNKI) were systematically searched up to March 15, 2025. RCTs comparing CHM with placebo or usual care in patients with confirmed post-COVID-19 syndrome were included. Primary outcomes were symptom severity measured by the Visual Analogue Scale (VAS); secondary outcomes included relief rates of cough, fatigue, chest tightness, dyspnea, insomnia, and exercise intolerance. Data were pooled using a random-effects model, and heterogeneity was assessed using I[2] statistics.<br><br>RESULTS: Ten RCTs involving 2401 patients were included. CHM showed a greater reduction in VAS scores compared to controls (MD&#x2009;=&#x2009;-1.03; 95% CI -2.10 to 0.03; P&#x2009;=&#x2009;0.0577), with higher heterogeneity (I[2]&#x2009;=&#x2009;92%). Although this result did not reach conventional statistical significance, it suggests a potentially meaningful clinical trend favoring CHM. Subgroup analysis indicated both short-term and long-term CHM treatments improved VAS scores, with a stronger effect in long-term treatment. CHM significantly improved chest tightness (RR&#x2009;=&#x2009;1.40; 95% CI 1.21-1.61; P&#x2009;<&#x2009;0.0001; I[2]&#x2009;=&#x2009;0%) and insomnia (RR&#x2009;=&#x2009;1.23; 95% CI 1.03-1.47; P&#x2009;=&#x2009;0.0216; I[2]&#x2009;=&#x2009;0%). A trend toward improvement was observed in fatigue (RR&#x2009;=&#x2009;1.58, 95% CI 0.95-2.64; P&#x2009;=&#x2009;0.0781) and dyspnea (RR&#x2009;=&#x2009;1.39, 95% CI 0.99-1.95; P&#x2009;=&#x2009;0.0554), although these results did not reach statistical significance. No significant difference was observed in terms of 6-min walking distance (MD&#x2009;=&#x2009;13.95&#xa0;m, 95% CI -11.64 to 39.55; P&#x2009;=&#x2009;0.2853). Adverse event rates were comparable between the herbal and control groups (RR&#x2009;=&#x2009;0.72, 95% CI 0.49-1.07; P&#x2009;=&#x2009;0.1052).<br><br>CONCLUSIONS: This meta-analysis indicates that Traditional Chinese Medicine (TCM) may help relieve certain post-COVID-19 symptoms, especially chest tightness and insomnia. Trends toward benefit were also noted for fatigue and dyspnea, though without statistical significance. Given the non-significant VAS results and high heterogeneity, these findings should be interpreted cautiously. Further large-scale, high-quality trials are needed to validate these outcomes and optimize treatment strategies.<br><br>https://www.crd.york.ac.uk/PROSPERO/home , CRD420251016442.},
}
@article {pmid40670209,
year = {2026},
author = {Zhou, YT and Chang, TH and Lin, CW and Shang, CY and Chen, SH and Shih, AT and Chen, FL and Gau, SS and Chang, LY},
title = {The impact of COVID-19 on psychophysiology and quality of life among children during omicron surge in Taiwan.},
journal = {Pediatrics and neonatology},
volume = {67},
number = {2},
pages = {164-170},
doi = {10.1016/j.pedneo.2025.04.005},
pmid = {40670209},
issn = {2212-1692},
mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Quality of Life ; Taiwan/epidemiology ; Female ; Male ; Child ; Adolescent ; Child, Preschool ; Fatigue/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Taiwan experienced an outbreak of the COVID-19 omicron variant in March 2022. We investigated the impact of COVID-19 on the psychophysiology and quality of life of children.<br><br>METHODS: We enrolled children under 18 from June to November 2023, dividing them into three groups based on their COVID-19 history: simple COVID, long COVID, and non-COVID. We collected demographic data and symptoms and conducted various surveys including the Modified Medical Research Council dyspnea scale, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, Patient Health Questionnaire-9, International Positive and Negative Affect Schedule Short-Form, Family APGAR, social and school behaviors, and family cohesion.<br><br>RESULTS: Of the 797 subjects, 573 (71.9 %) were confirmed cases, and 224 (28.1 %) were not infected. Fourteen percent (84/573) reported symptoms lasting over three months and were classified into the long COVID group. The long COVID group had significantly more physical and psychological symptoms than the non-COVID group (all p&#xa0;<&#xa0;0.05). Compared to the simple COVID and non-COVID groups, the long COVID group showed significantly more fatigue, higher severe mMRC grades, greater depression tendencies, higher negative affect scores, and lower well-being (all p&#xa0;<&#xa0;0.001). Additionally, depressive children in the COVID group experienced more stress about returning to school (p&#xa0;=&#xa0;0.01), more family dysfunction (p&#xa0;=&#xa0;0.01), less family support (p&#xa0;=&#xa0;0.008), and fewer problem-solving abilities in their families (p&#xa0;=&#xa0;0.008).<br><br>CONCLUSION: The long COVID group had more severe physical and psychological symptoms, family dysfunction, and school-related stress, indicating a need for further assistance.},
}
@article {pmid40670058,
year = {2025},
author = {Aretouli, E and Malik, M and Widmann, C and Parker, AM and Oh, ES and Vannorsdall, TD},
title = {Cognitive and mental health outcomes in long covid.},
journal = {BMJ (Clinical research ed.)},
volume = {390},
number = {},
pages = {e081349},
doi = {10.1136/bmj-2024-081349},
pmid = {40670058},
issn = {1756-1833},
mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Mental Health ; *Cognitive Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; *Anxiety/etiology ; Risk Factors ; *Depression/etiology ; },
abstract = {Roughly one in five adults who meet criteria for long covid present with objective or subjective cognitive dysfunction or elevated symptoms of depression or anxiety lasting ≥12 weeks from an acute covid illness. These neuropsychiatric sequelae have considerable functional consequences at the level of the individual, society, and the broader economy. Neuropsychiatric long covid symptoms are thought to be causally diverse, and a range of risk factors as well as biological, psychological, and environmental mechanisms have been hypothesized to contribute to symptom development and persistence. When present, objective cognitive deficits tend to be modest for most individuals, with some evidence suggesting increased risk of dysfunction and decline specifically for older adults with a history of severe acute illness. Longitudinal data suggest a delayed emergence of psychiatric symptoms may occur in the weeks and months after an acute covid illness. Emerging research points to the early recovery period as a potential window of opportunity for intervention to alter patient trajectories, though evidence based treatment remains lacking.},
}
@article {pmid40668129,
year = {2025},
author = {Wambui, D and Fiellin, M and Majka, C and Espineli, C and Flattery, J and Vergara, X},
title = {Prevalence and Risk Factors for Long COVID Among California Workers Captured by a Doctor's First Report-Based Surveillance System.},
journal = {Journal of occupational and environmental medicine},
volume = {67},
number = {12},
pages = {1060-1068},
doi = {10.1097/JOM.0000000000003497},
pmid = {40668129},
issn = {1536-5948},
mesh = {Humans ; California/epidemiology ; *COVID-19/epidemiology ; Male ; Middle Aged ; Risk Factors ; Female ; Adult ; Prevalence ; Cross-Sectional Studies ; SARS-CoV-2 ; *Occupational Diseases/epidemiology ; Young Adult ; Aged ; },
abstract = {OBJECTIVE: To understand prevalence and risk factors for long COVID among California workers.<br><br>METHODS: Using a cross-sectional study design, we analyzed 4496 Doctor's First Reports of Occupational Injury or Illness (DFRs) used for tracking work-related COVID-19 exposure or illnesses. Logistic regression was used to assess the risk factors.<br><br>RESULTS: With a prevalence of 11%, long COVID cases were slightly higher among male workers, workers aged between 45 and 54 years, and those in essential industries. Over 30 days of lost work was 13 times more prevalent among long COVID cases compared to acute cases. Age, presenting symptoms, and working in mixed essential industries increased long COVID risk.<br><br>CONCLUSION: These findings highlight long COVID burden on workers' health and productivity. Proactive measures are crucial to safeguard workers' health.},
}
@article {pmid40667921,
year = {2025},
author = {Barbosa, DAM and Ferraz-Pereira, KN and Conceição, EHD and Santos, REA and Lins, ID and Maior, CS and Araujo, AV and DO Vale Gomes, AL},
title = {Olfaction and taste disorders in Covid-19: prevalence, long-term persistence and impact on quality of life and eating habits of health professionals.},
journal = {Anais da Academia Brasileira de Ciencias},
volume = {97},
number = {3},
pages = {e20240392},
doi = {10.1590/0001-3765202520240392},
pmid = {40667921},
issn = {1678-2690},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Taste Disorders/epidemiology/etiology/virology ; *Olfaction Disorders/epidemiology/etiology/virology ; Female ; Male ; Prevalence ; Adult ; Middle Aged ; *Health Personnel/statistics &amp; numerical data ; *Quality of Life ; *Feeding Behavior ; SARS-CoV-2 ; Surveys and Questionnaires ; Brazil/epidemiology ; },
abstract = {The objective was to assess the prevalence and long-term persistence of olfactory and taste disorders among health professionals in the context of COVID-19. The study was carried out with 53 professionals, who were divided into 3 groups: (1) IgA and/or IgG positive for SARS-CoV-2 with loss of smell and/or taste (n=37); (2) IgA and/or IgG positive for SARS-CoV-2 without loss of smell and/or taste (n=7); and (3) IgA and IgG negative for SARS-CoV-2 (n=9). The collection of information was made using questionnaires by telephone contact. Symptoms of malaise and loss of smell and/or taste revealed an association with COVID-19 test results. Of the 53 participants, 39 reported impaired smell and taste, 37 with a positive diagnosis, and 2 with a negative diagnosis. Of the 53 professionals, 31 had Long COVID; the longest-lasting symptoms were loss of smell and taste. The study showed that there is a high prevalence of olfactory and/or taste alterations, both in the short and the long term, in individuals who tested positive for COVID-19.},
}
@article {pmid40667844,
year = {2025},
author = {Hung, CT and Wang, LM and Lee, YJ and Suk, CW and Kok, CY},
title = {Association of Nirmatrelvir/Ritonavir and the Risk of Long COVID Among US Adults: A Multicenter Retrospective Cohort Study.},
journal = {Journal of medical virology},
volume = {97},
number = {7},
pages = {e70494},
doi = {10.1002/jmv.70494},
pmid = {40667844},
issn = {1096-9071},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; Retrospective Studies ; Male ; *Ritonavir/therapeutic use ; Female ; Middle Aged ; *COVID-19 Drug Treatment ; Adult ; *Antiviral Agents/therapeutic use ; *COVID-19/epidemiology ; Aged ; United States/epidemiology ; SARS-CoV-2/drug effects ; },
abstract = {Nirmatrelvir/ritonavir (NMV-r) is an oral antiviral agent authorized for treating acute COVID-19, but its effectiveness in reducing long COVID risk remains uncertain. This multicenter retrospective cohort study aimed to evaluate the association between NMV-r and the risk of long COVID. Electronic health record data from the TriNetX US Collaborative Network were used. Adults aged ≥ 18 years with a positive COVID-19 test between January 1, 2022 and June 30, 2024 were included. NMV-r users were those who received NMV-r within 5 days of testing positive, while those who did not receive NMV-r within this period were the nonusers. The outcome was time to the first diagnosis of incident post-COVID conditions, including general, pulmonary, cardiac, thromboembolic, neurologic, mental, musculoskeletal, gastrointestinal, and kidney symptoms. Propensity score matching was performed to balance baseline characteristics and Cox proportional hazards models were used to estimate the risk of long COVID between NMV-r users and nonusers. Both groups included 218 825 patients after matching. Overall, the risk of long COVID was similar between NMV-r users and nonusers (HR, 0.99; 95% CI, 0.98-1.01). Symptom-specific analyses revealed mixed effects, with NMV-r use associated with an increased risk of cough and sleeping disorders but a decreased risk for other long COVID symptoms. Sensitivity analyses showed consistent results with the main analysis. In conclusion, NMV-r use was not associated with a reduced risk of long COVID. Future research is needed to explore its heterogeneous effects on post-COVID conditions.},
}
@article {pmid40667466,
year = {2025},
author = {Fradkin, T and Schmidt-Kastner, R},
title = {A data-mining analysis of host solute carrier family proteins in SARS-CoV-2 infection with reference to brain endothelial cells and the blood-brain barrier in COVID-19.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1563040},
pmid = {40667466},
issn = {1664-2295},
abstract = {BACKGROUND: The brain vasculature is a key player in neurological manifestations of COVID-19. Infection of brain endothelial cells with SARS-CoV-2 along with circulating cytokines may cause dysfunction of the blood-brain barrier (BBB). Solute carrier transporters (SLCs) in brain endothelial cells regulate substrate transport across the BBB. Here, it was hypothesized that transport functions of SLCs will be impaired by interactions with viral proteins, and subsequently, data-mining studies were performed.<br><br>METHODS: Virus-host protein-protein interaction data for SARS-CoV-2 infection were retrieved from the BioGRID database, filtered for SLCs, and then annotated for relevant expression in brain endothelial cells using a mouse brain transcriptomics database. Host SLCs expressed in brain endothelial cells were further explored using publicly available databases and information in the literature. Functional Annotation Clustering was performed using DAVID, and Enrichr served for pathway analysis. Substrates were retrieved from NCBI Gene. Links to monogenic disorders were retrieved from Online Mendelian Inheritance in Man&#x2122; and screened for disorders of the nervous system. Interactome data for viral proteins of SARS-CoV-2 were retrieved from BioGRID. Reports for host SLCs in viral receptor functions, viral entry mechanisms, and other major roles in the viral cycle were explored in databases (VThunter) and literature. ATP-binding cassette transporters (ABCs) were studied in parallel.<br><br>RESULTS: N&#x202f;=&#x202f;80 host SLCs showed relevant expression in brain endothelial cells whereby amino acid transporter stood out. N&#x202f;=&#x202f;24/80 host SLCs were linked to monogenic disorders of the nervous system. N&#x202f;=&#x202f;9/29 SARS-CoV-2 viral proteins had strong links to SLCs and key functions in viral infection (e.g., interferon response). SLCs serving as viral receptors and with closely associated functions were significantly enriched among all known listed viral receptors (chi-square test, p&#x202f;=&#x202f;0.001). Literature searches for host SLCs revealed involvement of a subset of SLCs in infection mechanisms for SARS-CoV-2 and more broadly for other viruses. N&#x202f;=&#x202f;17 host ABCs were found in brain endothelial cells where they may serve as efflux transporters.<br><br>DISCUSSION: This hypothesis-generating work proposes a set of N&#x202f;=&#x202f;80 host SLCs expressed in endothelial cells as contributors to BBB impairment after SARS-CoV-2 infection. Theoretically, persistent dysfunction of SLCs at the BBB, in particular insufficient transport of amino acids, could be one of many reasons for cognitive changes in long-COVID. Functions of SLCs in viral entry and associated roles deserve close attention.},
}
@article {pmid40663544,
year = {2025},
author = {, },
title = {Correction: Association between long COVID and nonsteroidal anti-inflammatory drug use by patients with acute-phase COVID-19: A nationwide Korea National Health Insurance Service cohort study.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0328398},
pmid = {40663544},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0312530.].},
}
@article {pmid40663038,
year = {2025},
author = {Avais, LS and Pacheco, EC and Gomes, LPOZ and Baldani, MH and Martins, CM and Waldman, EA and Gonzalez, JPJ and Steen, TY and Borges, PKO},
title = {Oral Manifestations in the Post COVID-19 Condition: A Systematic Review With Meta-Analysis.},
journal = {Reviews in medical virology},
volume = {35},
number = {4},
pages = {e70057},
pmid = {40663038},
issn = {1099-1654},
support = {//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; //Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
mesh = {Humans ; *COVID-19/complications/virology ; *Mouth Diseases/epidemiology/etiology/virology ; SARS-CoV-2/pathogenicity ; *Taste Disorders/epidemiology/virology ; Prevalence ; Xerostomia ; },
abstract = {Post-COVID-19 condition, or Long COVID, is characterised by symptoms persisting or emerging beyond 12 weeks after acute infection. Among over 200 reported symptoms, oral manifestations such as taste loss and dry mouth have been identified. This systematic review reports the frequency and characteristics of these symptoms. Registered in PROSPERO and following PRISMA guidelines, the review included observational studies on COVID-19-positive adults presenting oral symptoms in the post-COVID-19 condition. A search in six databases (Medline/PubMed, Embase, Web of Science, Cochrane, SCOPUS, and LILACS) was conducted in January 2024. Risk of bias was assessed using Joanna Briggs Institute's critical appraisal tools, and certainty of evidence via GRADE. A meta-analysis using the inverse variance method estimated oral symptom prevalence. Of 4552 articles, 107 were included. Taste dysfunction persisted in 8% (95% CI 6%-10%) of patients beyond 12 weeks. Combined taste and smell alterations had a prevalence of 17% (95% CI 13%-21%). Less frequent symptoms included hyposalivation, periodontitis, mouth ulcers, tongue mucosal changes, facial tingling, sensitivity in the trigeminal nerve, difficulty swallowing, and lesions in the hard palate. Taste alterations were the most commonly reported symptom, underscoring the need for clinical recognition and appropriate management by oral health professionals. Additionally, the wide range of other oral manifestations highlights the necessity for further research to better understand their prevalence, underlying mechanisms, and clinical implications in post-COVID-19 patients.},
}
@article {pmid40661336,
year = {2025},
author = {Rasouli, R and Hartl, B and Konecky, SD},
title = {Low-intensity ultrasound lysis of amyloid microclots in a lab-on-chip model.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1604447},
pmid = {40661336},
issn = {2296-4185},
abstract = {Amyloid fibrin(ogen) microclots are misfolded protein aggregates with β-sheet structures that have been associated with Long COVID and numerous thrombo-inflammatory diseases. These microclots persist in circulation and obstruct microvasculature, impair oxygen transport and promote chronic inflammation. Conventional thrombolytic therapies such as recombinant tissue plasminogen activator (rtPA) show limited efficacy against these microclots due to their structure and composition. In this study, we assess the impact of low intensity focused ultrasound (LIFU) stimulation on amyloid microclot fragmentation, the role of cavitation in this process and investigate whether microbubble-assisted ultrasound can enhance their lysis. Amyloid microclot models were generated using freeze-thaw cycles followed by incubation. Microclots were exposed to ultrasound waves at 150, 300, 500 kHz, and 1 MHz under four conditions: ultrasound alone (US), ultrasound with microbubbles (MB + US), ultrasound with rtPA (rtPA + US), and ultrasound with both microbubbles and rtPA (MB + rtPA + US). Low-frequency ultrasound at 150 kHz resulted in a significant clot lysis with up to three-fold reduction in both clot size and the number of large clots. The addition of microbubbles enhanced clot lysis at 150, 300, and 500 kHz. These findings suggest that ultrasound, particularly at 150 kHz is a promising method for amyloid microclot lysis. The combination of ultrasound with microbubbles and rtPA further improved clot fragmentation, rendering it a potential therapeutic tool for conditions like Long COVID.},
}
@article {pmid40660830,
year = {2025},
author = {Pagliano, P and Salzano, F and D'Amore, C and Spera, A and Conti, V and Folliero, V and Franci, G and Ascione, T},
title = {How do drug discovery scientists address the unmet need of long COVID syndrome therapeutics and what more can be done?.},
journal = {Expert opinion on drug discovery},
volume = {20},
number = {10},
pages = {1251-1265},
doi = {10.1080/17460441.2025.2534056},
pmid = {40660830},
issn = {1746-045X},
mesh = {Humans ; *COVID-19/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Drug Discovery/methods ; *COVID-19 Drug Treatment ; *Antiviral Agents/pharmacology/therapeutic use/administration &amp; dosage ; COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID (LC), also known as post-acute COVID-19 syndrome (PASC), has emerged as a significant public health concern characterized by persistent symptoms following SARS-CoV-2 infection. This condition affects regardless of initial illness severity and can significantly impair daily functioning. Understanding the implications of LC is crucial, given that approximately 6.9 % of adults reported related symptoms in 2022, with increased prevalence among women and individuals of Hispanic descent. The pathogenesis of LC is multifactorial, involving mechanisms such as endothelial dysfunction, chronic inflammation, immune dysregulation, and potential viral persistence. The clinical manifestations include fatigue, cognitive impairment, musculoskeletal pain, and sleep disturbances. Current research emphasizes the importance of early antiviral interventions and vaccines to mitigate the risk of developing LC. Despite promising therapies like anti-inflammatory agents and metabolic enhancers, the lack of established biomarkers complicates diagnosis and treatment.<br><br>AREAS COVERED: The authors provide an overview of the pathogenesis of LC and briefly review the currently available therapy. The authors then give their perspectives on how best future drug discovery efforts can be utilized to address the current demand for novel LC therapeutics to reduce the burden of this public health problem.<br><br>EXPERT OPINION: Progress has been made in understanding the pathophysiology and potential treatment options, as well as in establishing reliable biomarkers for potential tailored strategies. Future research should prioritize both pharmacological and non-pharmacological interventions to enhance patient outcomes and quality of life. Addressing these challenges is essential for developing comprehensive care protocols for individuals affected by LC.},
}
@article {pmid40660536,
year = {2025},
author = {Takezawa, H},
title = {Successful treatment of long-COVID postural tachycardia syndrome with epipharyngeal abrasive therapy in an adolescent patient: A case report.},
journal = {Medicine},
volume = {104},
number = {28},
pages = {e43333},
pmid = {40660536},
issn = {1536-5964},
mesh = {Adolescent ; Humans ; *COVID-19/complications ; *Postural Orthostatic Tachycardia Syndrome/therapy/etiology ; },
abstract = {RATIONALE: Postural orthostatic tachycardia syndrome (POTS) is a type of autonomic dysfunction that can occur following coronavirus disease (COVID-19) infection, particularly in adolescents. Treatment options are limited and often ineffective. We report a case of long COVID-associated POTS that responded favorably to epipharyngeal abrasive therapy (EAT), a treatment targeting chronic inflammation in the epipharynx.<br><br>PATIENT CONCERNS: A previously healthy adolescent developed persistent fatigue, headache, dizziness, insomnia, and orthostatic intolerance lasting over 3 months after a COVID-19 infection. The symptoms severely impaired daily functioning, rendering the patient bedridden.<br><br>DIAGNOSES: Based on clinical symptoms and a positive orthostatic test showing excessive postural tachycardia without hypotension, the patient was diagnosed with POTS associated with long COVID. Chronic epipharyngitis was also noted upon endoscopic examination.<br><br>INTERVENTIONS: The patient underwent weekly sessions of EAT for a total of 120 days. No additional pharmacologic treatment was provided during this period.<br><br>OUTCOMES: The patient showed marked improvement in symptoms, including increased tolerance to standing, reduced fatigue, and improved sleep quality. Objective improvement was confirmed through repeat orthostatic testing. The patient resumed school attendance and daily activities without limitation.<br><br>LESSONS: This case highlights the potential effectiveness of EAT in treating long COVID-related POTS in adolescents. EAT may offer a nonpharmacological treatment option by addressing underlying chronic epipharyngeal inflammation, a possible contributor to autonomic dysfunction.},
}
@article {pmid40656219,
year = {2025},
author = {Maccarone, MC and Contessa, P and Passarotto, E and Regazzo, G and Masiero, S},
title = {Balance rehabilitation and Long Covid syndrome: effectiveness of thermal water treatment vs. home-based program.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1588940},
pmid = {40656219},
issn = {2673-6861},
abstract = {INTRODUCTION: Balance concerns are increasingly recognized as a common presentation in patients with Long Covid. This study investigates the effects of two distinct rehabilitation programs on balance in a cohort of sixty participants experiencing medium-to-long-term symptoms following SARS-CoV-2 infection.<br><br>METHODS: Individuals were enrolled and randomly assigned to either a spa resort rehabilitation program or a supervised home-based rehabilitation program. The study assessed balance and proprioception by analyzing the center of pressure trajectory during a standing task performed with eyes open and closed before, after, and at a 3- and 6-month follow-up after the rehabilitation program.<br><br>RESULTS: Results indicated that, right after rehabilitation, participants who enrolled in the home-based program demonstrated more significant improvements in mean stay time and in the standard deviation of oscillations in the antero-posterior direction than those who enrolled in a spa-resort program. On the other hand, at the 3-month follow-up, individuals who enrolled in the spa-resort program exhibited improvements in the standard deviation of oscillations in the antero-posterior direction, indicating ongoing benefits over time.<br><br>DISCUSSION: These findings suggest that appropriate rehabilitation programs, whether at home or in spa resorts, can contribute to enhancing overall physical function in these patients.},
}
@article {pmid40656206,
year = {2025},
author = {Weaver, SS and Carry, M and Bertolli, J and Godino, J and Struminger, B and Taren, D and Scott, JD and Sharp, SP and Samaniego, J and Bean, DR and Issa, A and Lin, JS and Unger, ER and Ramers, CB},
title = {Assessing the influence of lived-experience experts on healthcare providers in a virtual community of practice: a qualitative study.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1562651},
pmid = {40656206},
issn = {2813-0146},
abstract = {Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other poorly understood post-acute infection syndromes (PAIS) can present with unexplained symptoms or conditions that may be misunderstood by healthcare providers, causing delays in diagnosis and care. To address these issues, the Centers for Disease Control and Prevention (CDC) funded the Long COVID and Fatiguing Illness Recovery Program (LC&amp;FIRP), initiated as a pilot project to assess whether providing tele-mentoring and other online education for primary care providers could help them improve the quality of life and support the recovery of their patients with these conditions. The LC&amp;FIRP multi-disciplinary team-based care approach is built on the Extension for Community Healthcare Outcomes (ECHO) learning model, which is an evidence-based virtual learning framework developed by the University of New Mexico and designed to disseminate and implement best practices, especially in under-resourced areas. A distinctive feature of LC&amp;FIRP was the inclusion of lived-experience experts. To explore the influence of lived-experience experts on the care patients received, we collected the educational recommendations provided by the lived-experience experts during webinar sessions (January 2022-March 2024) and grouped these by themes. The major themes that emerged included validation of patients' illness experience; attitudes and beliefs about Long COVID, ME/CFS, and PAIS; understanding patients' challenges and communicating with empathy; navigating referrals; recognizing and supporting disability; and supporting self-care. Investigators also interviewed patients of the Family Health Centers of San Diego (FHCSD) about their experiences receiving care from participating primary care providers and employed content analysis methods to code interview transcripts to identify themes among patients' perspectives. Positive comments from the patients about topics emphasized by the lived-experience experts provided evidence of providers' uptake and application of the experts' recommendations and support the value of involving lived-experience experts in medical education to improve health services.},
}
@article {pmid40656138,
year = {2025},
author = {Dhaouadi, N and Souissi, D and Yacoub, SB and Skhiri, A and Harizi, C and Fakhfakh, R and Boujdaria, R},
title = {Long COVID symptoms in the COVID unit of the emergency Department of Abderrahmen Mami Hospital in Tunisia: prevalence, main symptoms, and associated factors.},
journal = {The Pan African medical journal},
volume = {50},
number = {},
pages = {109},
pmid = {40656138},
issn = {1937-8688},
mesh = {Humans ; Tunisia/epidemiology ; Male ; Female ; Retrospective Studies ; *COVID-19/epidemiology/complications/physiopathology ; Middle Aged ; *Emergency Service, Hospital ; Prevalence ; Risk Factors ; Aged ; Adult ; Cohort Studies ; *Hospitalization/statistics &amp; numerical data ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: the COVID-19 pandemic has been evolving since 2019, affecting over 536 million individuals and causing more than six million deaths. After the acute phase, the onset or persistence of symptoms grouped under the name of long COVID is reported. The variability of symptomatology makes this a relevant subject of study, since more than one million cases of COVID-19 have been reported in Tunisia. The aim of our study was to determine the prevalence and potential risk factors for long COVID.<br><br>METHODS: we conducted a retrospective cohort study of patients admitted to the COVID unit of the emergency department of Abderrahmane Mami Hospital in Tunisia from April 1st to August 1st, 2021. The National Institute of Health Care definition of long COVID (November 2021) was adopted.<br><br>RESULTS: overall, 1,271 patients were admitted during the study period. After excluding deceased and unreachable patients by telephone, 454 were included in the analysis. The mean age was 58.6 &#xb1; 13.9 years, with a male predominance (53.7%). The prevalence of long COVID was 84.8%. The most common manifestations were breathing discomfort, asthenia, memory problems, tiredness, and arthralgia. In multivariable analysis, female sex was identified as a risk factor for long COVID (aOR: 1.732, 95% CI 1.002-2.995; p = 0.049).<br><br>CONCLUSION: the high prevalence of long COVID observed in our study highlights the need for post-COVID follow-up among affected patients. Our findings suggest that women had a higher risk of developing long COVID, indicating the benefit of individualized monitoring and care programs for this group.},
}
@article {pmid40655185,
year = {2025},
author = {Li, S and Zhao, H and Zhang, M and Yuan, T and Chai, D and Shen, Z and Qin, C and Li, Y and Pan, M},
title = {Long COVID in Elderly COPD Patients: Clinical Features, Pulmonary Function Decline, and Proteomic Insights.},
journal = {International journal of chronic obstructive pulmonary disease},
volume = {20},
number = {},
pages = {2337-2347},
pmid = {40655185},
issn = {1178-2005},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/physiopathology/diagnosis/complications/epidemiology ; *COVID-19/physiopathology/diagnosis ; Aged ; Male ; Female ; *Proteomics/methods ; *Lung/physiopathology ; SARS-CoV-2 ; Aged, 80 and over ; Time Factors ; Respiratory Function Tests ; Age Factors ; Risk Factors ; *Pneumonia, Viral/physiopathology/diagnosis ; Fatigue/physiopathology ; },
abstract = {BACKGROUND: Elderly patients with chronic obstructive pulmonary disease (COPD) face a heightened risk of developing long coronavirus disease (COVID); however the exact clinical characteristics and underlying mechanisms remain unclear.<br><br>METHODS: We enrolled 85 elderly COPD patients, of whom 43 reported newly onset persistent fatigue (the most dominant complaint of long COVID) within 1 year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and they were allocated to the Long-COVID group. The remaining 42 patients were assigned to the Control group. Patients completed questionnaires, pulmonary function tests, chest CT, routine laboratory tests, and blood proteomic analysis.<br><br>RESULTS: Long-COVID patients had a longer course of COPD (> 5 years, 76.8% vs 52.4%) and duration of SARS-CoV-2 infection (10.0 days vs 7.0 days) (All P < 0.05), higher symptom burden, worse pulmonary ventilation function and a more rapid decrease in DLCO (All P < 0.05). Proteomic analysis indicated disruptions in inflammation and energy metabolism, potentially underlying long COVID in these patients. The machine learning model identified wheezing, the duration of SARS-CoV-2 infection, EIF2S3 (eukaryotic translation initiation factor 2 subunit gamma), current FEV1/FVC (%), and the course of COPD as key features distinguishing Long-COVID patients, and exhibited excellent performance.<br><br>CONCLUSION: Elderly COPD patients with a longer COPD course and duration of COVID-19 are more prone to develop long COVID, with decreased pulmonary ventilation and diffusion ability. Disordered inflammation regulation and energy metabolism may be the potential mechanisms, highlighting the importance of monitoring inflammation and metabolic dysregulation in elderly COPD patients after recovery from COVID-19.},
}
@article {pmid40652046,
year = {2025},
author = {Godlewska, BR and Sylvester, AL and Emir, UE and Sharpley, AL and Clarke, WT and Williams, SR and Gonçalves, AJ and Raman, B and Valkovič, L and Cowen, PJ},
title = {Brain and muscle chemistry in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and long COVID: a 7T magnetic resonance spectroscopy study.},
journal = {Molecular psychiatry},
volume = {30},
number = {11},
pages = {5215-5226},
pmid = {40652046},
issn = {1476-5578},
support = {MR/K022202/1//RCUK | Medical Research Council (MRC)/ ; MR/K022202/1//RCUK | MRC | Medical Research Foundation/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/metabolism/diagnostic imaging ; Male ; *COVID-19/metabolism ; Female ; Magnetic Resonance Spectroscopy/methods ; Adult ; Middle Aged ; *Brain/metabolism ; *Muscle, Skeletal/metabolism ; Lactic Acid/metabolism ; Choline/metabolism ; SARS-CoV-2 ; Gyrus Cinguli/metabolism ; Energy Metabolism/physiology ; },
abstract = {Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a common debilitating medical condition, whose main symptoms - fatigue, post-exertional malaise and cognitive dysfunction - are also present in many cases of long COVID. Magnetic resonance spectroscopy (MRS) allows the insight into their pathophysiology through exploration of a range of biochemicals putatively relevant to aetiological processes, in particular mitochondrial dysfunction and energy metabolism. 24 patients with ME/CFS, 25 patients with long COVID and 24 healthy controls (HC) underwent brain (pregenual and dorsal anterior cingulate cortex, respectively, pgACC and dACC) and calf muscle MRS scanning at 7 Tesla, followed by a computerised cognitive assessment. Compared to HC, ME/CFS patients had elevated levels of lactate in both pgACC and dACC, while long COVID patients had lowered levels of total choline in dACC. By contrast, skeletal muscle metabolites at rest did not significantly differ between the groups. The changes in lactate in ME/CFS are consistent with the presence of energetic stress and mitochondrial dysfunction. A reduction in total choline in long COVID is of interest in the context of the recently reported association between blood clots and 'brain fog', and earlier animal studies showing that choline might prevent intravascular coagulation. Importantly, differences in findings between ME/CFS and long COVID suggest that the underlying neurobiological mechanisms, while leading to similar clinical presentations, may differ. An important implication is that patients with ME/CFS and those with fatigue in the course of long COVID should not be studied as a single group, at least until the mechanisms are better understood.},
}
@article {pmid40650463,
year = {2025},
author = {Zhang, B and Grau, M and Puta, C and Arvidsson, D and Arz, M and Böcker, J and Chilibeck, P and Forbes, SC and Kaiser-Stolz, C and McLaurin, N and Miyamoto-Mikami, E and Pesta, D and Pustowalow, W and Tanaka, H and Rittweger, J and Bloch, W},
title = {Post-COVID-19 Condition in Track and Field Master Athletes: Severity, Symptoms, and Associations With Quality of Life and C-Reactive Protein Levels.},
journal = {Scandinavian journal of medicine &amp; science in sports},
volume = {35},
number = {7},
pages = {e70106},
pmid = {40650463},
issn = {1600-0838},
support = {202306230030//China Scholarship Council/ ; //German Aerospace Center/ ; },
mesh = {Humans ; Male ; Female ; *Quality of Life ; *C-Reactive Protein/analysis/metabolism ; *COVID-19/complications/blood ; Middle Aged ; *Athletes ; Biomarkers/blood ; Adult ; Aged ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Surveys and Questionnaires ; Fatigue ; },
abstract = {Here, we assessed the prevalence of post-COVID-condition (PCC, also known as long-COVID) and investigated its associations with health-related quality of life and immune-related biomarkers in track and field masters athletes (MAs). A total of 216 MAs (114 males, 102 females; age: 58.3 ± 11.9 vs. 56.6 ± 11.7 years; BMI: 23.6 [22.2-24.8] vs. 21.3 [20.0-23.6] kg/m[2]) reported their post-COVID-conditions via the Post-COVID Syndrome Questionnaire (PCSQ). In a subgroup of 108 MAs, fasting blood samples were collected to assess C-reactive protein (CRP) levels as a biomarker of immune status (MAs-CRP). Based on their PCSQ sum score, MAs were divided into three groups: no/mild, moderate, and severe. Associations between PCC severity and sex, athletic specialty, and competition level were evaluated using Fisher's exact test. Forty-six (21%) MAs were identified with clinically relevant moderate-to-severe post-COVID-19 conditions (PCSQ score > 10.75). The most frequently reported symptoms included musculoskeletal pain (15%), sleep disturbance (13%), sensory or respiratory symptoms (11%), fatigue (11%), and flu-like symptoms (11%). PCC prevalence did not differ by sex, athletic specialties, training load, or prior competition level (all p > 0.05). MAs with moderate-to-severe PCC had significantly lower physical and mental component scores of quality of life compared with those with no or mild symptoms (p < 0.05). In the MAs-CRP subgroup, self-reported cardiac ailments and flu-like symptoms were significantly and positively associated with CRP levels (Spearman ρ = 0.27-0.30, all p < 0.01). Post-COVID-19 condition is associated with reduced quality of life in track and field masters athletes, independent of sex, prior competition levels, and training characteristics. Furthermore, low-grade inflammation based on CRP levels was associated with self-reported cardiac and flu-like symptoms.},
}
@article {pmid40649991,
year = {2025},
author = {Hein, ZM and Thazin, and Kumar, S and Che Ramli, MD and Che Mohd Nassir, CMN},
title = {Immunomodulatory Mechanisms Underlying Neurological Manifestations in Long COVID: Implications for Immune-Mediated Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {13},
pages = {},
pmid = {40649991},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/complications ; SARS-CoV-2/immunology ; *Neurodegenerative Diseases/immunology/etiology ; Blood-Brain Barrier/immunology ; Biomarkers ; Post-Acute COVID-19 Syndrome ; *Immunomodulation ; },
abstract = {The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood-brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus-immune-brain axis in long COVID and inform effective clinical management.},
}
@article {pmid40649860,
year = {2025},
author = {Li, GH and Han, FF and Kalafatis, E and Kong, QP and Xiao, W},
title = {Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.},
journal = {International journal of molecular sciences},
volume = {26},
number = {13},
pages = {},
pmid = {40649860},
issn = {1422-0067},
support = {Research Fund//Open Medicine Foundation/ ; },
mesh = {Humans ; *COVID-19/metabolism ; *Fatigue Syndrome, Chronic/metabolism/drug therapy ; Aspartic Acid/metabolism/therapeutic use ; SARS-CoV-2 ; Metabolomics ; Metabolic Networks and Pathways ; Asparagine/metabolism ; Male ; Metabolome ; Female ; Alanine/metabolism ; Adult ; Proline/metabolism ; },
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway. Further, in silico knockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood. Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME/CFS and Long COVID for future clinical trials.},
}
@article {pmid40649148,
year = {2025},
author = {de Brito, FAM and Laranjeira, C and Rossoni, SL and Ali, AM and Salci, MA and Carreira, L},
title = {Spatial Distribution and Post-COVID-19 Health Complications in Older People: A Brazilian Cohort Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {13},
pages = {},
pmid = {40649148},
issn = {2077-0383},
support = {FCT-Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia, I.P. (UIDB/05704/2020 and UIDP/05704/2020) and by the Scientific Employment Stimulus-Institutional Call - [https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 6 May 2025]//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; grant number: 001/2023//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; },
abstract = {Background/Objectives: In the aftermath of the COVID-19 pandemic, individuals infected with SARS-CoV-2 have progressively displayed a range of symptoms linked to protracted COVID during the post-acute phase of illness. Concurrently, in several nations globally, the phenomenon of population aging has been intensifying. In this scenario, the aged population has become both vulnerable and high-risk during the acute phase of COVID-19, and faces significant dangers associated with long-COVID. This study seeks to analyze the incidence and spatial distribution of health complications in older people affected by COVID-19, in the first year of the pandemic (2020), in the State of Paraná, as well as to identify the factors associated with the development of cardiovascular, neurological, respiratory, and metabolic diseases. Method: An observational and retrospective study was carried out in the Brazilian state of Paraná. Participants were randomly selected from two databases. A total of 893 older people (≥60 years) participated in the study 12 months after acute COVID-19 infection. Telephone questionnaires were applied between March and December 2021. The Moran index test, logistic regression, and Poisson models were used to analyze the data. Results: In terms of age, most participants (66%) were between 60 and 69 years old, 25.8% were between 70 and 79 years old, and 8.2% were 80 years old or older. Most participants were female (51.2%), white (98.1%), had a partner (69.8%), and had been hospitalized due to COVID-19 (59.3%). Cardiovascular diseases were the most frequent in the population (39.5%), followed by metabolic diseases (27.3%). The long-term use of medication was associated with the development of metabolic diseases (aOR = 9.8), cardiovascular diseases (aOR = 6.6), and diseases in multiple organic systems (aOR = 3.2); living alone was associated with neurological diseases (aOR = 2.5), and the age group of 80 years or older (aOR = 2.4) was associated with cardiovascular events. The spatial distribution showed that complications in body groups are distributed randomly among the health regions of the state, with no influence from neighboring locations. Conclusions: Post-COVID-19 health complications are more frequent in older adults who have comorbidities and long-term medication use. Therefore, long-term monitoring of these individuals and investment in public policies for rehabilitation and prevention of complications are necessary.},
}
@article {pmid40648596,
year = {2025},
author = {Tarver, WL and Hu, X and MacEwan, SR and Gaughan, AA and McAlearney, AS},
title = {Long COVID Patients' Perceptions of Social Support in Their Work and Personal Lives: A Qualitative Study.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {13},
pages = {},
pmid = {40648596},
issn = {2227-9032},
support = {U54CA260582/CA/NCI NIH HHS/United States ; },
abstract = {Background: The onset and persistence of Long COVID can lead to cognitive and functional impairment, contributing to illness-induced employment and work disparities. Understanding how social support influences these issues can inform care strategies and support continued workforce participation. Objectives: This study explored perceptions of social support among patients with Long COVID. Methods: Semi-structured interviews were conducted with 21 patients receiving care at a post-COVID recovery clinic. Patient perspectives on social support in their work and personal lives were analyzed using both inductive and deductive thematic analysis. Findings were organized under the following five dimensions of social support theory: tangible support, emotional support, informational support, appraisal support, and belonging support. Results: Patients received positive tangible, emotional, and informational support from family, friends, and credible sources. However, patients also described receiving negative appraisal support from their personal lives and workplaces when others misunderstood the scope and duration of their limitations due to Long COVID. This negative appraisal support often labeled them as lazy or underperforming, leading to both personal and professional challenges to their self-esteem. Regarding companionship support, participants reported challenges keeping in touch with others and being less social. Conclusions: Social support impacts Long COVID patients' abilities to cope with the trauma of their experiences. Understanding the sources of and barriers to social support for Long COVID patients may inform strategies to enhance their care and well-being. Future interventions should offer opportunities for family, friends, and employers of Long COVID patients to learn about what it means to live with the illness.},
}
@article {pmid40645616,
year = {2025},
author = {Rohner, S and Schnepper, R and Meinlschmidt, G and Schaefert, R and Mayr, M and Bopp, K and Meienberg, A},
title = {Basel Long COVID Cohort Study (BALCoS): protocol of a prospective cohort study.},
journal = {BMJ open},
volume = {15},
number = {7},
pages = {e093981},
pmid = {40645616},
issn = {2044-6055},
mesh = {Female ; Humans ; Male ; *COVID-19/complications/psychology/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Psychometrics ; Research Design ; Switzerland/epidemiology ; Observational Studies as Topic ; },
abstract = {INTRODUCTION: The recent pandemic caused by SARS-CoV-2 had a profound global impact. While many individuals recovered from COVID-19, some developed long-lasting symptoms that significantly disrupted daily life. The WHO defines this condition as post-COVID-19 condition (PCC). Common symptoms include fatigue, dyspnoea, sleep disturbances and cognitive difficulties. Increasing evidence suggests that PCC is a multifactorial condition, shaped not only by biomedical but also psychological and social factors. This article presents the protocol of the Basel Long COVID Cohort Study (BALCoS), which aims to improve understanding of PCC by capturing clinical, functional and psychosocial aspects through repeated assessments over the course of 1 year.<br><br>METHODS AND ANALYSIS: BALCoS is a prospective, single-site cohort study. Inclusion criteria include either a probable or confirmed history of SARS-CoV-2 infection with persistent symptoms consistent with the WHO definition of PCC, sufficient German language skills and age &#x2265;18 years. At baseline, we collected detailed information on previous SARS-CoV-2 infections, symptom history, reinfections, COVID-19 vaccination status and pre-existing medical conditions. The study includes standardised psychometric assessments, physical performance tests, ecological momentary assessments (EMAs), neurocognitive testing and blood sample collection. Assessments are scheduled at baseline and at 3-month, 6-month and 12-month follow-up. All participants complete psychometric assessments at each time point. Blood samples are only collected at baseline. Neurocognitive testing and physical performance measures are collected at baseline and 12-month follow-up for in-person participants only. Participants who are unable to attend in person complete a remote version of the study, excluding these in-clinic assessments. EMAs are initiated the day after each time point and consist of eight questions over 10 consecutive days. The study is exploratory in nature, with a target sample size of 120 participants. BALCoS is part of the Horizon Europe Long COVID project, a multinational interdisciplinary research consortium integrating mechanistic, clinical and interventional studies.<br><br>ETHICS AND DISSEMINATION: The study was approved by the Ethics Commission of Northwest and Central Switzerland (BASEC-ID: 2023-00359) and is registered at ClinicalTrials.gov (ID: NCT05781893). All participants provide written informed consent. Study findings will be disseminated through peer-reviewed publications.<br><br>TRIAL REGISTERATION NUMBER: NCT05781893.},
}
@article {pmid40645608,
year = {2025},
author = {Cabello Fernandez, C and Didone, V and Slama, H and Dupuis, G and Fery, P and Delrue, G and Lesoinne, A and Collette, F and Willems, S},
title = {Profiles of Individuals With Long COVID Reporting Persistent Cognitive Complaints.},
journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists},
volume = {40},
number = {8},
pages = {1455-1472},
pmid = {40645608},
issn = {1873-5843},
support = {LCOV21-1303//Belgian Health Care Knowledge Centre/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Cognitive Dysfunction/etiology ; *COVID-19/complications/psychology ; Fatigue/etiology ; Neuropsychological Tests ; Quality of Life/psychology ; Sleep Wake Disorders/etiology ; Surveys and Questionnaires ; },
abstract = {OBJECTIVE: A subset of COVID-19 patients continues to experience cognitive difficulties 24 months post-infection. The factors driving these symptoms are complex, and the underlying pathophysiology is unclear. This study aimed to characterize individuals with Long COVID reporting cognitive issues.<br><br>METHOD: One hundred twenty-three patients underwent a comprehensive neuropsychological evaluation resulting from the baseline of an RCT study (COVCOG), along with questionnaires assessing cognitive complaints, fatigue, sleep difficulties, quality of life, psychological distress, and impact on daily activities. Latent Profile Analyses on cognitive scores were conducted to investigate the presence of different patient profiles. Robust analyses of variance and Pearson's chi-square examined the profiles' effects on demographic variables and questionnaire scores.<br><br>RESULTS: Patients had had predominantly mild to moderate infections (87.8%) and were assessed an average of 20.9 (&#xb1;8.6) months post-infection. Neuropsychological assessment showed cognitive impairment in at least one domain in 72% of the patients, mainly in attention and executive functions. Over 80% reported sleep problems and fatigue, 97% concentration problems, and some 80% memory and word-finding problems. The self-report questionnaires also revealed significant complaints. Three profiles emerged (all ps&#xa0;<&#x2009;.001). Profiles 1 and 2 both experienced widespread cognitive issues; Profile 1 patients expressed more complaints about cognitive functioning and daily fatigue (all ps&#xa0;<&#x2009;.045). Patients in Profile 3 were more frequently men (all ps&#xa0;<&#x2009;.049) with a specific impairment of verbal long-term memory and fewer complaints.<br><br>CONCLUSIONS: The study identifies three different profiles of individuals with Long COVID, highlighting the need for comprehensive evaluations including neuropsychological, psychological, somatic, and functional aspects to implement effective, tailored interventions. Clinicaltrials.gov: NCT05167266.},
}
@article {pmid40645034,
year = {2025},
author = {Delpierre, C and Lemogne, C and Steichen, O and Tebeka, S and Makovski, TT and Coste, J},
title = {Influence of socioeconomic position on the relationship between long COVID and health-related quality of life: A nationwide random sampling survey in France in autumn 2022.},
journal = {Social science &amp; medicine (1982)},
volume = {382},
number = {},
pages = {118368},
doi = {10.1016/j.socscimed.2025.118368},
pmid = {40645034},
issn = {1873-5347},
mesh = {Humans ; France/epidemiology ; Male ; Female ; *Quality of Life/psychology ; Adult ; Middle Aged ; *COVID-19/epidemiology/psychology/complications ; Surveys and Questionnaires ; Aged ; *Social Class ; Socioeconomic Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; Young Adult ; },
abstract = {Socioeconomic position (SEP) is associated with long COVID risk and health-related quality of life (HRQoL). SEP may influence the relationship between long COVID and HRQoL, but evidence is lacking. Our study therefore evaluated the influence of SEP on the relationship between long COVID or post-COVID-19 condition (PCC) and HRQoL in a representative sample of the general French population. After the Omicron waves in autumn 2022, a representative sample of 1448 adults infected with SARS-CoV-2 was assessed for post-COVID-19 symptoms, demographics, SEP, health factors and HRQoL using the PROMIS-29 questionnaire measuring HRQoL in eight domains (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference and pain intensity). PCC was defined according to the World Health Organisation. A conceptual model of the relationship between PCC and impaired HRQoL was proposed. Modifying effects of age, sex and SEP variables (geographic origin, education, household size, occupational category, employment status, household income) on the relationship between PCC and HRQoL were tested in the framework of this model. PCC, low education level and household income negatively impacted overall HRQoL and 5/8 PROMIS-29 domains (depression, fatigue, sleep disturbance, social participation and pain intensity). PCC-induced HRQoL impairment was significantly higher among people without a long tertiary education, unemployed individuals, business owners and entrepreneurs and people from mainland France. Healthcare providers and policymakers should better account for the differential impact of long COVID on HRQoL according to SEP. They should promote strategies to reduce health inequalities and lessen the burden of this condition in the general population.},
}
@article {pmid40644485,
year = {2025},
author = {Siddik, AB and Faisal, A and Khan, AH and Alam, MMM and Nayeem, J and Kulsum, U and Mukta, SA and Kawser, Z and Hasan, I and Azad, K and Hossain, M and Kar, S and Sultana, N and Alam, MR and Mustafa, A and Habib, MT and Ryan, ET and Qadri, F and Hassan, MR},
title = {Pulmonary function and comparative SARS-CoV-2 RBD-specific IgG antibody response among the COVID-19 recovered group.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0318959},
pmid = {40644485},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/immunology/physiopathology ; Male ; Female ; SARS-CoV-2/immunology ; *Immunoglobulin G/immunology/blood ; Middle Aged ; Case-Control Studies ; *Antibodies, Viral/immunology/blood ; Prospective Studies ; Adult ; Respiratory Function Tests ; Aged ; *Lung/physiopathology ; Pandemics ; *Betacoronavirus/immunology ; *Spike Glycoprotein, Coronavirus/immunology ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for millions of deaths and substantial morbidity worldwide. Several studies report that up to 50% of individuals who recover from acute SARS-CoV-2 infection experience a plethora of long-COVID symptoms that may persist for weeks, months, or even up to a year. Abnormal pulmonary function is one of the most critical manifestations of long-COVID, even after recovering from COVID-19. Understanding the long-term pulmonary consequences and immune response among individuals recovering from COVID-19, who experienced disease severity ranging from mild to severe, is crucial for comprehensive post-recovery care and vaccination strategies.<br><br>METHODS: This prospective case-control study included 29 individuals who had recovered from COVID-19 with a history of mild to severe symptoms and 64 controls. Assessments of pulmonary functional measures, such as FVC, FEV1, FEV1/FVC ratio, FEF, MEF, and PEF were carried out following recovery from COVID-19. Additionally, IgG antibody responses were examined by ELISA for up to six months through multiple follow-ups following two doses of vaccination, with an additional follow-up 30 days after the booster dose (third dose).<br><br>RESULTS: Pulmonary functional abnormalities were prevalent in the recovered group, which had previously exhibited varying symptom severity (53% mild, 66% moderate, and 50% severe) compared to the control group (23%). Higher IgG antibody titers were observed among the recovered group, with significantly elevated titers in severe and moderate cases following vaccination. After vaccination, the recovered group showed significantly higher titers at day 14, particularly in the severe (1418 IU/mL) and moderate (1390 IU/mL) groups, compared to the control group (968 IU/mL) (p&#x2009;<&#x2009;0.005). Notably, antibody titers were negatively correlated with pulmonary function test (PFT) parameters such as Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1). All groups experienced a significant (p&#x2009;<&#x2009;0.005) decrease in antibody titers within 90-120 days after receiving two doses of vaccination. After five to six months, antibody titers returned to baseline levels, highlighting the importance of vaccination and additional booster doses regardless of previous infection history. Overall, our study underscores the significance of pulmonary function assessment post-COVID-19 recovery for long-term respiratory health and emphasizes the importance of vaccination regardless of infection history.<br><br>CONCLUSION: To assess the impact of long-COVID on respiratory health, this study underscores the importance of evaluating pulmonary function in individuals, whether they had symptomatic or asymptomatic COVID-19. Furthermore, the findings from the immune response analysis highlight the critical role of vaccination, regardless of infection history, as a key strategy of pandemic preparedness.},
}
@article {pmid40643736,
year = {2025},
author = {Venter, C and Pretorius, JH and Kell, DB and Pretorius, E},
title = {A novel metacyte metafer classifier for platelet morphology using long COVID as a model.},
journal = {Journal of thrombosis and thrombolysis},
volume = {},
number = {},
pages = {},
pmid = {40643736},
issn = {1573-742X},
support = {18//Balvi Foundation/ ; B31//Balvi Foundation/ ; NNF20CC0035580//Novo Nordisk Fonden/ ; },
}
@article {pmid40643301,
year = {2025},
author = {Beka, SG and Griffiths, RF and Myers, JA and Skirrow, PM},
title = {Appropriate Screening Tests to Assess Post-COVID-19 Cognitive Dysfunction in Aeromedical Settings.},
journal = {Aerospace medicine and human performance},
volume = {96},
number = {5},
pages = {414-424},
doi = {10.3357/AMHP.6500.2025},
pmid = {40643301},
issn = {2375-6322},
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/diagnosis/etiology ; *Pilots/psychology ; *Aerospace Medicine ; *Neuropsychological Tests ; SARS-CoV-2 ; Mass Screening ; },
abstract = {INTRODUCTION: Post-COVID-19, 10-20% of individuals may experience long-term symptoms (some having cognitive deficits), even after mild or nonsymptomatic infection. A sufficiently sensitive screening test of cognitive function, based on the typical cognitive effects of COVID-19 and skills considered most relevant to pilot performance, would be highly beneficial to be used alongside other performance checks. This study aimed to identify appropriate screening tests for post-COVID-19 cognitive dysfunction.<br><br>METHODS: Initially, a systematic search and narrative review identified 13 screening tools that are likely to be effective in screening pilots for post-COVID-19 neurocognitive impairment. Following a more in-depth evaluation of the identified tools, five tests including the Trail Making Test, Symbol Digit Modalities Test, Stroop Color Word Test, Psychomotor Vigilance Test, and Paced Auditory Serial Addition Test were chosen for a Delphi evaluation exercise. A two-round modified Delphi process was undertaken with international aviation medicine and psychology experts to obtain a consensus on which of the identified tests would be appropriate to screen for cognitive dysfunction in pilots.<br><br>RESULTS: Based on evaluation of literature review findings and Delphi consultation with subject matter experts, the Trail Making Test and Symbol Digit Modalities Test were identified as quick and suitable screening tests likely to detect post-COVID-19 cognitive dysfunction.<br><br>DISCUSSION: These tools are objective, have good utility, are available in multiple versions, and assess cognitive abilities relevant to pilot performance. Their use for screening in aeromedical examinations would be further supported by confirming their ability to reliably detect neurocognitive impacts associated with COVID-19. Beka SG, Griffiths RF, Myers JA, Skirrow PM. Appropriate screening tests to assess post-COVID-19 cognitive dysfunction in aeromedical settings. Aerosp Med Hum Perform. 2025; 96(5):414-424.},
}
@article {pmid40642241,
year = {2025},
author = {Shaheen, A and Shaheen, N and , and Shoib, S and Saeed, F and Buhari, M and Bharmauria, V and Flouty, O},
title = {Deep learning analysis of long COVID and vaccine impact in low- and middle-income countries (LMICs): development of a risk calculator in a multicentric study.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1416273},
pmid = {40642241},
issn = {2296-2565},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *COVID-19/prevention &amp; control/epidemiology ; *COVID-19 Vaccines/administration &amp; dosage ; *Deep Learning ; Depression/epidemiology ; *Developing Countries ; Risk Assessment/methods ; SARS-CoV-2 ; Surveys and Questionnaires ; Vaccination/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic affecting millions worldwide. This study aims to bridge the knowledge gap between acute and chronic symptoms, vaccination impact, and associated factors in patients across different low- and middle-income countries (LMICs).<br><br>MATERIALS AND METHODS: The study included 2,445 participants aged 18&#x202f;years and older, testing positive for COVID-19. Data collection involved screening for medical histories, testing records, symptomatology, and persistent symptoms. Validated instruments, including the DePaul Symptom Questionnaire (DSQ-2) and the Patient Health Questionnaire-9 (PHQ-9), were used. We applied a self-supervised and unsupervised deep neural network to extract features from the questionnaire. Gradient boosted machines (GBM) model was used to build a risk calculator for chronic fatigue syndrome (CFS), depression, and prolonged COVID-19 symptoms.<br><br>RESULTS: Out of the study cohort, 68.1% of the patients had symptoms lasting longer than 2&#x202f;weeks. The most frequent symptoms were loss of smell (46.8%), dry cough (40.1%), loss of taste (37.8%), headaches (37.2%), and sore throat (28.9%). The patients also reported high rates of depression (47.7%), chronic fatigue (6.5%), and infection after vaccination (23.7%). Factors associated with CFS included sex, age, and smoking. Vaccinated individuals demonstrated lower odds of experiencing prolonged COVID-19 symptoms, CFS, and depression. The predictive models achieved a high area under the curve (AUC) scores of 0.87, 0.82, and 0.74, respectively.<br><br>CONCLUSION: The findings underscore the significant burden of long-term symptoms such as chronic fatigue and depression, affecting a considerable proportion of individuals post-infection. Moreover, the study reveals promising insights into the potential benefits of vaccination in mitigating the risk of prolonged COVID-19 symptoms, CFS, and depression. Overall, this research contributes valuable knowledge towards comprehensive management and prevention efforts amidst the ongoing global pandemic.<br><br>CLINICAL TRIAL REGISTRATION: Clinical trials.gov, NCT05059184.},
}
@article {pmid40641353,
year = {2025},
author = {Silletti, F and Koire, A and Ma, C and Lin, HC and Mittal, L and Roffman, JL and Erdei, C and Musso, P and Liu, CH},
title = {COVID-19 experiences and persistent maternal mental health symptoms: Examining the role of long COVID, self-efficacy, and partner support.},
journal = {Development and psychopathology},
volume = {},
number = {},
pages = {1-10},
doi = {10.1017/S0954579425000379},
pmid = {40641353},
issn = {1469-2198},
abstract = {Perinatal women were particularly impacted during the pandemic, with documented consequences for both mothers' and infants' well-being. This study investigated the longitudinal relationships between COVID-19-related experiences during the peripartum and women's depression and anxiety symptoms at long-term follow-up. We explored the moderating role of long COVID for the first time, along with perceived partner support and maternal self-efficacy. A sample of 190 US perinatal women completed a survey from May 21, 2020, to September 15, 2021 (T1), and again between December 14, 2022, and February 14, 2024 (T2). The survey assessed COVID-19-related experiences, mental health, long COVID, maternal self-efficacy, partner support, and life events. Anxiety was associated with both long COVID and decreased partner support, and both depression and anxiety were linked to lower self-efficacy. A larger number of COVID-19-related experiences during the peripartum period was associated with higher levels of later depression and anxiety symptoms. Long COVID exacerbated these links, while partner support buffered them. Maternal self-efficacy dampened the association between COVID-19-related experiences and subsequent depression, but not anxiety. Findings suggest that COVID-19 has lasting effects on perinatal women's mental health, with partner support and maternal self-efficacy acting as resilience factors, highlighting the potential benefit of targeted interventions to enhance these modifiable factors.},
}
@article {pmid40640905,
year = {2025},
author = {Ewing, AG and Joffe, D and Blitshteyn, S and Brooks, AES and Wist, J and Bar-Yam, Y and Bilodeau, S and Curtin, J and Duncan, R and Faghy, M and Galland, L and Pretorius, E and Salamon, S and Buonsenso, D and Hastie, C and Kane, B and Khan, MA and Lal, A and Lau, D and MacIntyre, R and McFarland, S and Munblit, D and Nicholson, J and Ollila, HM and Putrino, D and Rosario, A and Tan, T and , },
title = {Correction: Long COVID clinical evaluation, research and impact on society: a global expert consensus.},
journal = {Annals of clinical microbiology and antimicrobials},
volume = {24},
number = {1},
pages = {41},
pmid = {40640905},
issn = {1476-0711},
}
@article {pmid40640033,
year = {2025},
author = {Giunta, S and Giuliani, A and Sabbatinelli, J and Olivieri, F},
title = {A multidimensional immunological perspective on long COVID.},
journal = {Cytokine &amp; growth factor reviews},
volume = {84},
number = {},
pages = {1-11},
doi = {10.1016/j.cytogfr.2025.07.001},
pmid = {40640033},
issn = {1879-0305},
mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Inflammation/immunology ; Cytokines/immunology ; Post-Acute COVID-19 Syndrome ; Autoantibodies/immunology/blood ; },
abstract = {Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction ("brain fog"), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation. In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging - a chronic, low-grade inflammation associated with aging - which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition. In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID.},
}
@article {pmid40636591,
year = {2025},
author = {James, L and Philip, AM and John, JO and Olafimihan, AG and Esparza, F},
title = {Clinical Characteristics and Long-Term Effects of COVID-19 in a Secondary Care Hospital in South India: A Study of Post-acute Sequelae and Pulmonary Outcomes.},
journal = {Cureus},
volume = {17},
number = {6},
pages = {e85576},
pmid = {40636591},
issn = {2168-8184},
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant global morbidity, with long-term effects known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID syndrome. This study investigates the clinical characteristics and long-term effects of COVID-19 in a rural South Indian population. Conducted in a secondary healthcare setting in Kerala, India, the study involved 65 subjects who had tested positive for COVID-19 more than 90 days prior. Participants completed a detailed questionnaire on common COVID-19 and PASC symptoms and underwent pulmonary function testing. Data analysis included descriptive statistics, point-biserial correlation, and logistic regression. The prevalence of PASC symptoms was found to be 55.4%, with dyspnea being the most common symptom. Healthcare workers experienced a lower prevalence of PASC (41.9%) compared to non-healthcare workers (67.6%). Logistic regression indicated higher odds of PASC in men, non-healthcare workers, and those with comorbidities, though these findings were not statistically significant. Pulmonary function tests revealed reduced forced vital capacity in 23.1% of subjects. The study highlights the significant impact of long COVID on this unvaccinated population prior to the Delta wave, emphasizing the need for ongoing research to understand and manage the long-term effects of COVID-19.},
}
@article {pmid40636057,
year = {2025},
author = {Berentschot, JC and Bek, LM and Drost, M and van den Berg-Emons, RJG and Braunstahl, GJ and Ribbers, GM and Aerts, JGJV and Hellemons, ME and Heijenbrok-Kal, MH and , },
title = {Health outcomes up to 3 years and post-exertional malaise in patients after hospitalization for COVID-19: a multicentre prospective cohort study (CO-FLOW).},
journal = {The Lancet regional health. Europe},
volume = {53},
number = {},
pages = {101290},
pmid = {40636057},
issn = {2666-7762},
abstract = {BACKGROUND: Many patients experience long-lasting health problems after COVID-19. The study aimed to assess 3-year trajectories of a comprehensive set of patient-reported outcome measures (PROMs) in patients hospitalized for COVID-19, particularly focusing on the 2- to 3-year trajectory. Additionally, we evaluated prevalence of post-exertional malaise (PEM) at 3 years, its risk factors, co-occurring health problems, and the 3-year trajectories of patients with and without PEM.<br><br>METHODS: The CO-FLOW multicentre prospective cohort study followed up adults hospitalized for COVID-19 in 7 hospitals, located in the Netherlands. Study assessments were performed at 3, 6, 12, 24, and 36 months post-discharge, conducted between July 1, 2020, and May 22, 2024. PROMs on recovery, symptoms, fatigue, mental health, cognition, participation, sleep quality, work status, health-related quality of life (HRQoL), and PEM were collected. Generalized estimating equations were used to assess health trajectories and multivariable logistic regression to identify risk factors for PEM.<br><br>FINDINGS: In total, 299/344 (87%) patients completed the 3-year follow-up and were included in the analysis. Complete recovery rates increased (p < 0.001), from 12% at 3 months to 24% at 3 years. Symptoms of impaired fitness, fatigue, and muscle weakness (all p < 0.0019) and PROMs for fatigue score, participation, return to work, and HRQoL (all p < 0.005) improved significantly over time, while PROMs for cognitive failures worsened (p < 0.001). Between the 2- and 3-year visits, memory problems (OR 1.4 [1.1-1.7], p < 0.001), and scores of fatigue (MD +1.0 [0.4-1.6], p = 0.002), cognitive failures (MD +2.2 [0.9-3.4], p < 0.001), and SF-36 mental component summary (-2.2 [-3.1 to -1.3], p < 0.001) significantly worsened. At 3 years, 66% of patients experienced fatigue, 63% impaired fitness, 59% memory problems, and 53% concentration problems. PROMs showed that 62% reported poor sleep quality, 55% fatigue, and 28% cognitive failures. PEM was reported by 105/292 (36%) patients at 3 years; risk factors were female sex (OR 3.4 [95% CI 1.9-6.0], p < 0.001), pre-existing pulmonary disease (3.0 [1.7-5.6], p < 0.001), physical inactivity pre-COVID-19 (2.3 [1.2-4.1], p = 0.008), and ICU treatment for COVID-19 (1.8 [1.02-3.0], p = 0.04). Concurrent fatigue, cognitive failures, and dyspnea were more common in patients with (42%) than without (6%) PEM. Patients with PEM showed poor health outcomes throughout the entire follow-up period, including worsening fatigue and HRQoL during the third year.<br><br>INTERPRETATION: Many health problems persisted up to 3 years post-discharge, with self-reported fatigue and cognitive problems worsening in the third year. PEM was common, and linked to a more severe phenotype of long COVID. These findings highlight the urgent need to optimize treatment options and investigate underlying pathological mechanisms of COVID-19.<br><br>FUNDING: The Netherlands Organisation for Health Research and Development (ZonMw); Rijndam Rehabilitation; Laurens.},
}
@article {pmid40635708,
year = {2025},
author = {Huff, HV and Roberts, H and Bartrum, E and Norato, G and Grayson, N and Fleig, K and Wilkerson, MJ and Stussman, BJ and Nath, A and Walitt, B},
title = {Prevalence and severity of neurologic symptoms in Long-COVID and the role of pre-existing conditions, hospitalization, and mental health.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1562084},
pmid = {40635708},
issn = {1664-2295},
abstract = {BACKGROUND: Long-COVID refers to ongoing, relapsing, or new symptoms present 30 or more days after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study examined the prevalence and severity of neurologic symptoms at greater than 1 month following acute SARS-CoV-2 infection and the influence of pre-existing neurologic and psychiatric conditions, current depression and anxiety status, and hospitalization on the presence and severity of these symptoms.<br><br>METHODS: This prospective cohort study recruited primarily self-referred Long-COVID participants with confirmed SARS-CoV-2 infection. Online questionnaires inquiring about pre-existing conditions, neurologic symptoms and their severity pre, during and post COVID-19, and current anxiety and depression screening were completed by 213 participants at a median time of 8&#x202f;months after infection. Descriptive analyses and prevalence modeling were performed.<br><br>RESULTS: The most frequent neurologic symptoms post COVID-19 were fatigue, concentration/memory difficulties, unrefreshed sleep, and dysarthria/word finding difficulties (73.2-86.4%). Neurologic symptoms were highly prevalent with significantly greater odds post COVID-19 compared to pre for all symptoms and higher prevalence at time periods farther from infection, including those implicit in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. Several severe neurologic symptoms were significantly more prevalent post COVID-19. Moderate to severe anxiety (34%) and depression (27%) were observed post COVID-19. Preexisting neurologic or psychiatric conditions did not demonstrate any significant difference in neurologic symptom prevalence post COVID-19. Those who met criteria for moderate or severe anxiety post COVID-19 had a significant difference in prevalence of fatigue, sensitivity to touch and unrefreshed sleep. Similarly, fatigue, concentration/memory difficulty and unrefreshed sleep were more prevalent in moderate to severe depression. There were no significant differences in neurologic symptom prevalence in a hospitalized group when compared to non- hospitalized.<br><br>CONCLUSION: Long-COVID has a high burden of long lasting and severe neurological sequelae. These sequelae are independent of pre-existing self-reported neurologic and psychiatric conditions, as well as previous hospitalization. Current moderate to severe anxiety and depression status can impact fatigue, cognition, and sleep post COVID-19. Focus on the biological impact of SARS-CoV-2 on the nervous system will be essential in ameliorating the tremendous symptom burden left in the wake of the COVID-19 pandemic.<br><br>CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov, identifier: NCT04573062.},
}
@article {pmid40635480,
year = {2025},
author = {Cho, OH},
title = {Unraveling the immune responses in long COVID through cytokine profiling.},
journal = {The Korean journal of internal medicine},
volume = {40},
number = {4},
pages = {531-532},
pmid = {40635480},
issn = {2005-6648},
}
@article {pmid40629217,
year = {2026},
author = {Kwon, J and Mensah, J and Milne, R and Rayner, C and Lawrence, RR and De Kock, J and Sivan, M and Petrou, S and , },
title = {Health economic outcomes and national economic impacts associated with Long COVID in England and Scotland.},
journal = {The European journal of health economics : HEPAC : health economics in prevention and care},
volume = {27},
number = {1},
pages = {149-166},
pmid = {40629217},
issn = {1618-7601},
support = {COV-LT2-0016//National Institute for Health and Care Research/ ; },
mesh = {Humans ; England/epidemiology ; *COVID-19/economics/epidemiology ; Female ; Male ; Scotland/epidemiology ; Middle Aged ; Aged ; Adult ; Patient Reported Outcome Measures ; SARS-CoV-2 ; Quality-Adjusted Life Years ; *Health Care Costs/statistics &amp; numerical data ; Post-Acute COVID-19 Syndrome ; Cost of Illness ; },
abstract = {BACKGROUND: Two million people in the UK suffer from Long COVID (LC), imposing substantial health economic impacts. This study aimed to: 1) assess longitudinal changes in health utility scores and economic costs of LC, and number of services received at LC specialist clinics and clinic region to capture care intensity; 2) assess whether volume of services received responded to health needs; and 3) estimate the national economic impact of LC.<br><br>METHODS: LC patients from 10 specialist clinics participated in the LOCOMOTION study. Patient-reported outcomes measures (EQ-5D-5L, C19-YRS and Health Economics Questionnaire) were completed on a digital platform. Associations were assessed between changes in economic outcomes (EQ-5D-3L utility, health economic costs) and number/type of LC specialist services received and region. Per-person values of quality-adjusted life-year losses, public sector costs, productivity losses and informal care costs were multiplied by LC prevalence to estimate national economic impacts.<br><br>RESULTS: There was a statistically significant reduction in public sector costs over time. There was no significant association between the number of specialist services received and change in health utility scores. LC specialist clinic and outpatient service utilisation corresponded to health need and had significant regional variation after controlling for health need. LC is associated with a substantial economic impact nationally, estimated at &#xa3;8.1 billion annually and &#xa3;24.2 billion since its emergence, comparable to the annual cost of &#xa3;9.4 billion for stroke.<br><br>CONCLUSION: The effectiveness of LC specialist clinic services warrants further research. The substantial national economic impact of LC warrants a nationwide LC care strategy.},
}
@article {pmid40628861,
year = {2025},
author = {Kumar, N and Lam, CN and Lee, R and Unger, JB and Sood, N},
title = {The association between baseline physical and mental health and the risk of postacute sequelae of COVID-19 infection.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24374},
pmid = {40628861},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; Female ; Male ; Middle Aged ; *Mental Health ; Risk Factors ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/isolation &amp; purification ; Depression/epidemiology ; Health Status ; },
abstract = {Post-acute sequelae of COVID-19 infection (PASC) is a widely reported phenomenon wherein symptoms of COVID-19 infection persist for four weeks or more beyond acute infection. Risk factors at baseline (prior to infection) for the development of PASC are not well understood. This study aimed to identify baseline demographic, physical and mental health characteristics associated with the development of PASC. We identified 351 participants who reported contracting COVID-19 and 145 that experienced PASC symptoms. Baseline physical health, mental health, and demographic data were collected for all participants. Risk factors for the development of PASC were identified using multivariable logistic regression. PASC was associated with lower income, Hispanic ethnicity, younger age, and respiratory conditions (asthma or COPD). Worse self-reported mental health status, a diagnosis of depression, and a higher patient health questionnaire-2 (PHQ-2) score were also associated with PASC. We then used latent class analysis and identified two subtypes of PASC, one with fewer PASC symptoms (n = 112) and another with many PASC symptoms (n = 33). Risk factors for membership in each class were different, but a past diagnosis of depression predicted membership in both classes compared to those without PASC. A diagnosis of depression was more strongly associated with the "many symptoms" class compared to the "few symptoms" class. We find that several mental health and demographic risk factors are linked to PASC. More research is necessary to understand both the two subtypes of PASC identified in our analysis, and the underlying relationship between COVID-19 infection and PASC.},
}
@article {pmid40627396,
year = {2025},
author = {Shankar, V and Wilhelmy, J and Curtis, EJ and Michael, B and Cervantes, L and Mallajosyula, V and Davis, RW and Snyder, M and Younis, S and Robinson, WH and Shankar, S and Mischel, PS and Bonilla, H and Davis, MM},
title = {Oxidative stress is a shared characteristic of ME/CFS and Long COVID.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {28},
pages = {e2426564122},
pmid = {40627396},
issn = {1091-6490},
support = {NA//Khosla family gift fund/ ; U19-AI057229//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; U19 AI057229/AI/NIAID NIH HHS/United States ; NA//HHMI (HHMI)/ ; R01 AI139550/AI/NIAID NIH HHS/United States ; S10 OD026831/OD/NIH HHS/United States ; S10 RR027431/RR/NCRR NIH HHS/United States ; 5R01AI139550//HHS | NIH (NIH)/ ; },
mesh = {Humans ; *Oxidative Stress ; Female ; Male ; *COVID-19/metabolism ; Reactive Oxygen Species/metabolism ; *Fatigue Syndrome, Chronic/metabolism ; Adult ; Middle Aged ; Mitochondria/metabolism ; SARS-CoV-2 ; Lymphocytes/metabolism ; },
abstract = {Over 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition marked by fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). With no clinically approved treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in 25 healthy controls, 27 ME/CFS, and 20 LC donors, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, especially in the memory subset. Using a combination of flow cytometry, RNA-seq, mass spectrometry, and systems chemistry analysis, we observed aberrations in reactive oxygen species (ROS) clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase protein levels, and glutathione peroxidase 4-mediated lipid oxidative damage. Strikingly, these redox pathways changes show sex-specific trends. While ME/CFS females exhibit higher total ROS and mitochondrial calcium levels, males have normal ROS levels, with pronounced mitochondrial lipid oxidative damage. In females, these higher ROS levels correlate with T cell hyperproliferation, consistent with the known role of elevated ROS in initiating proliferation. This hyperproliferation can be attenuated by metformin, suggesting this Food and Drug Administration (FDA)-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Moreover, these results suggest a shared mechanistic basis for the systemic phenotypes of ME/CFS and LC, which can be detected by quantitative blood cell measurements, and that effective, patient-tailored drugs might be discovered using standard lymphocyte stimulation assays.},
}
@article {pmid40627388,
year = {2025},
author = {Eckey, M and Li, P and Morrison, B and Bergquist, J and Davis, RW and Xiao, W},
title = {Patient-reported treatment outcomes in ME/CFS and long COVID.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {28},
pages = {e2426874122},
pmid = {40627388},
issn = {1091-6490},
support = {230275//Open Medicine Foundation (OMF)/ ; },
mesh = {Humans ; *COVID-19/therapy/complications/epidemiology ; *Patient Reported Outcome Measures ; *Fatigue Syndrome, Chronic/therapy/epidemiology ; Male ; Female ; Middle Aged ; Adult ; Treatment Outcome ; SARS-CoV-2 ; Aged ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are persistent multisystem illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments may prove helpful in identifying management strategies that can improve patient care and generate new avenues for research. Here, we present the results of an ME/CFS and long COVID treatment survey with responses from 3,925 patients. We assess the experiences of these patients with more than 150 treatments in conjunction with their demographics, symptoms, and comorbidities. Treatments with the greatest perceived benefits are identified. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of long COVID reported postexertional malaise (PEM). Furthermore, treatment responses between these two patient groups were significantly correlated (R[2] = 0.68). Patient subgroups, characterized by distinct symptom profiles and comorbidities, exhibited increased responses to specific treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants. This study underscores the symptomatic and therapeutic similarities between ME/CFS and long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. While this study does not provide recommendations for specific therapies, in the absence of approved treatments, insights from patient-reported experiences provide urgently needed real-world evidence for developing targeted patient care therapies and future clinical trials.},
}
@article {pmid40626567,
year = {2025},
author = {Lam, ICH and Chai, Y and Man, KKC and Lau, WCY and Luo, H and Lin, X and Yin, C and Chui, CSL and Li, X and Zhang, Q and Chan, EWY and Wan, EYF and Wong, ICK},
title = {The short-, medium- and long-term risk and the multi-organ involvement of clinical sequelae after COVID-19 infection: a multinational network cohort study.},
journal = {Journal of the Royal Society of Medicine},
volume = {118},
number = {7},
pages = {213-229},
pmid = {40626567},
issn = {1758-1095},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Cardiovascular Diseases/epidemiology ; *COVID-19/complications/epidemiology ; France/epidemiology ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; },
abstract = {ObjectivesTo generate comprehensive evidence on the risk of clinical sequelae involving different organ systems over time after coronavirus disease 2019 (COVID-19) infection.DesignMultinational retrospective cohort study.SettingElectronic medical records from the US, UK, France, Germany and Italy standardised to the Observational Medical Outcomes Partnership Common Data Model.ParticipantsA total of 303,251 individuals with a COVID-19 infection between 1 December 2019 and 1 December 2020 and propensity score matched non-COVID-19 comparators from 22,108,925 eligible candidates.Main outcome measuresIncidence of 73 clinical sequelae involving multiple organ systems including the respiratory, cardiovascular, dermatological and endocrine systems over the short- (0-6 months), medium- (6-12 months) and long-term (1-2 years) after COVID-19 infection. The hazard ratio (HR) and 95% confidence interval (95% CI) of individual disease outcomes were estimated using Cox proportional hazard regression.ResultsIndividuals with COVID-19 incurred a greater risk of clinical sequelae involving multiple organ systems including respiratory (France HR 2.23, 95%CI [2.10,2.37] to Italy 13.13 [11.80,14.63]), cardiovascular (Germany 1.39 [1.30,1.50] to US 1.79 [1.74,1.85]) and dermatological (UK 1.13 [1.01,1.25] to Italy 1.77 [1.42,2.21]) disorder over the short-term. While the risk of clinical sequelae has largely subsided during the medium-term, the risk of cardiovascular- (US 1.16 [1.11,1.21], France 1.10 [1.01,1.19]) and endocrine- (US 1.18 [1.12,1.24], Germany 1.15 [1.03,1.29]) related complications may continue to persist for up to two years.ConclusionsThrough a network of multinational healthcare databases, this study generated comprehensive and robust evidence supporting the extensive multi-organ involvement of post-COVID-19 condition over the short-term period and the reduction in risk for most complications over the medium- and long-term.},
}
@article {pmid40624269,
year = {2025},
author = {Seibert, S and Eckert, I and Widmann, CN and Ebrahimi, T and Bösl, F and Franke, C and Prüss, H and Schultze, JL and Petzold, GC and Shirvani, O},
title = {Validity of the test for attentional performance in neurological post-COVID condition.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24208},
pmid = {40624269},
issn = {2045-2322},
mesh = {Humans ; Middle Aged ; Male ; Adult ; Female ; Aged ; *Attention/physiology ; *COVID-19/complications/psychology ; *Neuropsychological Tests ; Adolescent ; Young Adult ; *Cognitive Dysfunction/diagnosis ; SARS-CoV-2 ; ROC Curve ; },
abstract = {Neurological post-COVID condition (PCC) often involves attentional deficits that impact daily functioning. Traditional paper-based tests, like the Trail-Making Test (TMT), may inadequately capture these impairments due to their short duration and dependence on numerical and alphabetic sequencing. This study evaluates the validity of three subtests of the computerized Test for Attentional Performance (TAP) as alternatives for detecting attentional impairments in PCC. In the ongoing NEURO LC-19 DE study, 108 subjects aged 18 to 79 years, with PCC-related cognitive complaints (n = 67, 73% f) and healthy controls (n = 41, 56% f) underwent neuropsychological testing. The prevalence of impairment and classification ability of the TAP subtests were evaluated alongside standard paper-based tests, including the TMT and Montreal Cognitive Assessment, using receiver operating characteristic (ROC) analysis and regression. The TAP subtests identified significant impairments in sustained attention and processing speed in one-third of PCC patients, surpassing traditional tests in sensitivity, and classifying PCC with an AUC of 78%. Omissions in sustained attention significantly differentiated groups (OR = 1.14, p = 0.016, 95% CI [1.02-1.26]). Fatigue correlated with poorer performance on speed and accuracy (r > 0.30, p < 0.05). Cognitive slowing is prevalent in neurological PCC but is scarcely captured by conventional assessments. The TAP's computerized format with automated norming and independence from alphanumeric stimuli shows promise in improving the discriminatory ability for identifying attentional deficits in PCC patients.},
}
@article {pmid40623643,
year = {2025},
author = {Sisti, JS and Packard, SE and Yung, J and Metzler, J},
title = {Trajectories of post-traumatic stress disorder symptoms and subsequent risk of long COVID in the World Trade Center Health Registry.},
journal = {Journal of affective disorders},
volume = {390},
number = {},
pages = {119814},
doi = {10.1016/j.jad.2025.119814},
pmid = {40623643},
issn = {1573-2517},
mesh = {Humans ; *Stress Disorders, Post-Traumatic/epidemiology/psychology ; *COVID-19/epidemiology/psychology ; Male ; Female ; *September 11 Terrorist Attacks/psychology ; Registries ; Adult ; Middle Aged ; Risk Factors ; New York City/epidemiology ; SARS-CoV-2 ; Resilience, Psychological ; },
abstract = {OBJECTIVE: Though the etiology of long COVID is not well-understood, pre-existing mental health conditions have been identified as risk factors. We examined associations between post-traumatic stress disorder symptoms (PTSS) and long COVID among individuals exposed to the World Trade Center disaster.<br><br>METHODS: We used group-based trajectory modeling to identify five PTSS trajectories (resilient, low-stable, remitted, delayed onset, chronic-high) among enrollees in the World Trade Center Health Registry (2003-04 to 2020-2021). Among 5361 enrollees who reported a COVID-19 infection, we used modified Poisson regression to estimate risk ratios (RRs) and 95&#xa0;% confidence intervals (95&#xa0;% CI) for associations of PTSS trajectories with self-reported long COVID symptoms.<br><br>RESULTS: In 2022-23, 41&#xa0;% of enrollees reported long COVID symptoms. In models adjusted for sociodemographic characteristics and self-reported diagnosed physical health conditions and depression, associations with long COVID were observed for all trajectories compared to the resilient trajectory, which was characterized by very low PTSS at all points. RRs were similar among trajectory groups characterized by a high lifetime prevalence of probable PTSD (RRremitted&#xa0;=&#xa0;1.83, 95&#xa0;% CI&#xa0;=&#xa0;1.64, 2.04; RRdelayed&#xa0;=&#xa0;1.86, 95&#xa0;% CI&#xa0;=&#xa0;1.67, 2.06; RRchronic&#xa0;=&#xa0;1.80, 95&#xa0;% CI&#xa0;=&#xa0;1.59, 2.03). Risk of long COVID was also elevated among individuals in the low-stable trajectory group, who had a lower lifetime prevalence of probable PTSD (RR&#xa0;=&#xa0;1.46, 95&#xa0;% CI&#xa0;=&#xa0;1.35, 1.58).<br><br>CONCLUSION: Risk of long COVID is elevated among individuals with a history of PTSS, including among those whose symptoms have improved. Populations at high risk of PTSD, including those exposed to traumatic events, may benefit from targeted screening to identify those with long COVID.},
}
@article {pmid40622937,
year = {2025},
author = {Bahillo Ruiz, E and Pérez-Pérez, L and Cárdaba-García, RM and Durantez-Fernández, C and Jiménez-Navascués, L and Velasco-Gonzalez, V and Muñoz-Del Caz, A and Madrigal, M and Olea, E},
title = {Relationships between fatigue severity scale (FSS)/ scale for mood assessment (EVEA) and clinical manifestations in spanish long-COVID patients.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0324075},
pmid = {40622937},
issn = {1932-6203},
mesh = {Humans ; Female ; *Fatigue/epidemiology/psychology ; Male ; *COVID-19/psychology/complications/epidemiology ; Middle Aged ; Spain/epidemiology ; Adult ; Aged ; Severity of Illness Index ; Surveys and Questionnaires ; Depression/epidemiology ; SARS-CoV-2/isolation &amp; purification ; *Mood Disorders/epidemiology ; Anxiety/epidemiology ; Affect ; },
abstract = {AIM: This study aims to investigate the influence of fatigue and mood disturbances in Spanish long-COVID patients and to establish relationships between these factors and other clinical manifestations.<br><br>METHOD: A descriptive correlational study was conducted using a self-administered online questionnaire. The sample was obtained through non-random convenience sampling, comprising 374 participants from various regions of Spain. Data collection occurred between July 2, 2022, and November 30, 2022. The questionnaire collected demographic information and inquired about symptomatology as well as self-perception of health status. Validated scales, namely the Fatigue Severity Scale (FSS) and the Scale for Mood Assessment (EVEA), were utilized.<br><br>RESULTS: The non-random sample consisted of 374 participants from diverse regions of Spain, of whom 79.9% were women. Over 70% of participants reported fatigue, while the EVEA revealed high scores in sadness-depression (4.94&#x2009;&#xb1;&#x2009;2.82) and anxiety (4.57&#x2009;&#xb1;&#x2009;2.88). Significant relationships were identified between fatigue and mood disturbances and neurological, psychological, locomotive, and pain symptoms.<br><br>CONCLUSIONS: Given the impact of the syndrome on psychological, social and economic spheres, regular monitoring of patients with long COVID is crucial. This study corroborates previous research findings and is notable for demonstrating the persistence of symptoms for over a year. Mood disorders, such as anxiety and depression, are closely related to physical symptoms, highlighting the need for holistic healthcare approaches.},
}
@article {pmid40622467,
year = {2025},
author = {Chatterjee, D and Maparu, K},
title = {Long COVID syndrome: exploring therapies for managing and overcoming persistent symptoms.},
journal = {Inflammopharmacology},
volume = {33},
number = {7},
pages = {4097-4113},
pmid = {40622467},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/therapy/complications/epidemiology/physiopathology ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Risk Factors ; },
abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is a growing global health concern, affecting 10-35% of COVID-19 survivors. Characterized by persistent multisystem symptoms lasting beyond 12 weeks, common manifestations include fatigue, dyspnea, chest pain, cognitive impairment, depression, and anxiety. The underlying pathophysiology remains unclear but is likely to involve immune dysregulation, persistent inflammation, endothelial dysfunction, gut dysbiosis, and viral persistence. This review examines the epidemiology, risk factors, and clinical manifestations of long COVID, with a focus on its impact on cardiopulmonary, neurological, and mental health. Therapeutic approaches include pharmacological interventions such as anti-inflammatory agents, antioxidants, neuroprotective drugs, and repurposed medications. Non-pharmacological strategies, such as physical rehabilitation, cognitive therapy, dietary modification, and emerging therapies like stem cell therapy, as well as immunomodulatory approaches, offer promising avenues for recovery. We also highlight ongoing clinical trials evaluating targeted therapies for long-term COVID syndrome. Future research should focus on elucidating the pathophysiological mechanisms, identifying biomarkers, and optimizing personalized treatment strategies for long-term COVID-19 management.},
}
@article {pmid40622013,
year = {2025},
author = {Salmam, I and Desmeules, F and Perreault, K and Zahouani, I and Beaulieu-Bonneau, S and Campeau-Lecours, A and Paquette, JS and Deslauriers, S and Tittley, J and Drouin, G and Best, K and Roy, JS},
title = {Trajectories of Physical Disabilities Over 6 Months in Patients With Long COVID.},
journal = {Physical therapy},
volume = {105},
number = {8},
pages = {},
pmid = {40622013},
issn = {1538-6724},
support = {//R&#xe9;seau Provincial de Recherche en Adaptation-R&#xe9;adaptation (REPAR)/ ; 466876/CAPMC/CIHR/Canada ; },
mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; Female ; *Quality of Life ; Middle Aged ; Longitudinal Studies ; Prospective Studies ; Adult ; SARS-CoV-2 ; *Persons with Disabilities ; Aged ; Post-Acute COVID-19 Syndrome ; Fatigue ; },
abstract = {IMPORTANCE: Understanding the long-term impact of long COVID on physical function and health-related quality of life (HRQoL) is essential to guide clinical care and rehabilitation.<br><br>OBJECTIVE: The objective of this study was to compare physical capacity over time among adults in 3 groups: those without COVID-19 (control group [CG]), those who recovered from COVID without persistent symptoms (short COVID group [SCG]), and those with long COVID (long COVID group [LCG]). A secondary objective was to identify baseline predictors of 6-month HRQoL in the LCG.<br><br>DESIGN: This study was a prospective longitudinal cohort study.<br><br>SETTING: In-laboratory assessments were conducted at baseline, 3 months, and 6 months, at either the Center for Interdisciplinary Research in Rehabilitation and Social Integration (Quebec City) or the Orthopedic Clinical Research Unit (Montreal).<br><br>PARTICIPANTS: A total of 360 age- and sex-matched adults (n&#x2009;=&#x2009;120 per group), including individuals without a history of COVID-19 (CG), those with short COVID (symptom resolution within 4&#xa0;weeks, SCG), and those with persistent symptoms &#x2265;12&#xa0;weeks (LCG) participated in the study.<br><br>INTERVENTION/EXPOSURE: Participants were categorized based on their COVID-19 history and symptom duration and no intervention or exposure was applied.<br><br>MAIN OUTCOMES AND MEASURES: Self-reported outcomes measuring HRQoL, comorbidities, sleep quality, pain, and fatigue, along with objective measures such as grip strength, Short Physical Performance Battery (SPPB), 6-min walk test (6MWT), and perceived exertion (Modified Borg Scale) during the 6MWT, were collected. Daily averages for resting heart rate, step count, and minutes of intensive activity were recorded over 7&#xa0;days using a fitness tracker watch. Generalized estimating equations were used for longitudinal comparisons, and recursive partitioning analysis for predicting HRQoL factors.<br><br>RESULTS: Significant time&#x2009;&#xd7;&#x2009;group interactions were observed for HRQoL, sleep quality, pain, fatigue, SPPB, and 6MWT. Although the LCG showed significant improvements across these outcomes, only the reduction in fatigue reached a clinically meaningful level, whereas the other groups remained stable. A group effect was detected for all outcomes, except for heart rate and minutes of intensive activity, with the LCG consistently showing lower scores across all follow-ups. Recursive partitioning analysis identified 2 baseline predictors of HRQoL at 6&#xa0;months in the LCG: self-reported fatigue and daily step count.<br><br>CONCLUSIONS AND RELEVANCE: These findings highlight the persistent impairments in adults with long COVID and emphasize early HRQoL predictor identification to anticipate long-term needs and adjust treatment plans accordingly.},
}
@article {pmid40621076,
year = {2025},
author = {Seo, IH and Park, B and Kim, H and Heo, SJ and Jung, DH},
title = {The effects of G1899 Korean red ginseng extract powder on long COVID for acute COVID19 infection: A randomized, double-blind, placebo-controlled trial.},
journal = {Journal of ginseng research},
volume = {49},
number = {4},
pages = {470-477},
pmid = {40621076},
issn = {1226-8453},
abstract = {BACKGROUND: In this study, we investigated the therapeutic potential effects of G1899 Korean Red Ginseng Extract Powder(G1899) on long COVID in a general population using flow cytometry and follow-up by questionnaire.<br><br>METHODS: We conducted a 12-week clinical pilot study on 220 COVID19 patients who were recently infected. The study was completed by 108 participants in the G1899 group and 108 participants in the placebo group. Participants were randomized 1:1 to the G1899 and placebo groups. We evaluated the long COVID by questionnaire including GAD-7, FSS and BFI-K at baseline and 12 weeks. To investigate the changes in the levels of CD4/CD8 T cell ratio and regulatory T cell population, multicolor flow cytometry was performed.<br><br>RESULTS: The G1899 group showed significantly chronic fatigue symptoms relieving compared with placebo group at 12 weeks in women. The CD4/CD8 ratio increased significantly in the G1899 group, rising from 1.71 (95&#xa0;% CI: 1.35-2.07) at Visit 1 to 2.31 (95&#xa0;% CI: 1.83-2.78) at Visit 4 (p&#xa0;=&#xa0;0.0029). Unlike the G1899 group, there was a significant reduction in the Treg population, from 2.02&#xa0;% at Visit 1-1.22&#xa0;% at Visit 4 (p&#xa0;=&#xa0;0.0005) in the placebo group.<br><br>CONCLUSION: These findings suggest that G1899 has beneficial effects on the amelioration of long COVID symptoms, with more prominent effects observed in women. Although the changes in Treg population were not statistically significant in the G1899 group, the significant reduction observed in the placebo group suggests a potential protective effect of G1899 against Treg depletion.},
}
@article {pmid40619575,
year = {2025},
author = {Turana, Y and Shen, R and Darmawan, O and Barus, JFA},
title = {Harlequin Syndrome in a Post-COVID-19 Infection Elderly: A Case Report.},
journal = {Acta neurologica Taiwanica},
volume = {34},
number = {3},
pages = {176-180},
doi = {10.4103/ANT.ANT_113_0023},
pmid = {40619575},
issn = {1028-768X},
mesh = {Humans ; Male ; *COVID-19/complications ; Aged, 80 and over ; *Autonomic Nervous System Diseases/etiology/diagnosis ; *Flushing/etiology/diagnosis ; *Hypohidrosis/etiology/diagnosis ; SARS-CoV-2 ; },
abstract = {Harlequin syndrome (HS) is a rare autonomic nervous system disorder caused by blockage of the unilateral upper-thoracic sympathetic pathway that provides vasomotor and sudomotor supply to the face. Infection and the subsequent immune response cascade are proposed as triggers for arterial occlusion due to microvascular ischemia, underlying the pathophysiology of HS in adult cases. We report this unusual case to inform readers about the possibility of causation and pathophysiological pathway of HS in post-COVID-19 infection. An 82-year-old male patient developing HS post-COVID-19 infection, presented with sudden left-hemifacial redness 4 days before admission, with similar recurrent complaints ten times since his resolved symptomatic COVID-19. Other physical and neurological examinations are regular. Laboratory results showed mild microcytic hypochromic anemia with D-dimer five-folds higher than normal limits. D-dimer fluctuated elevation during HS attacks is a sign of inflammatory process and increased thromboembolic risk in a long-COVID. The patient's history of chronic hypercholesterolemia with old lacunar infarction in the brain's frontal lobes suggested worsening microvascular disturbance. The patient was diagnosed as HS in post-COVID-19. To the author's knowledge, this is the first reported HS case in Indonesia and the second HS case post-COVID-19. Moreover, we also provide a schematic approach to the possible pathological process of HS in post-COVID-19. Post-COVID-19 infection is highly possible causing HS because of its persistent pathological inflammation leading to dysautonomic sympathetic fibers. However, its involvement in a specific pathophysiological pathway that disturbs the cervical sympathetic chain and causes HS, without presenting as systemic dysautonomia, should be further investigated.},
}
@article {pmid40618677,
year = {2025},
author = {Seco-Gonzalez, A and Antelo-Riveiro, P and Bravo, SB and Domínguez-Santalla, MJ and Rodríguez-Ruiz, E and Piñeiro, &#xc1; and Garcia-Fandino, R},
title = {Comprehensive molecular characterization of post-COVID condition: Immunoglobulin suppression and persistent SARS-CoV-2 antigens as key pathophysiological drivers.},
journal = {Journal of infection and public health},
volume = {18},
number = {10},
pages = {102870},
doi = {10.1016/j.jiph.2025.102870},
pmid = {40618677},
issn = {1876-035X},
mesh = {Humans ; *COVID-19/immunology/physiopathology/complications/blood ; *SARS-CoV-2/immunology ; Male ; Middle Aged ; Proteomics ; Female ; *Antigens, Viral/immunology/blood ; Mass Spectrometry ; Aged ; Adult ; *Immunoglobulins/blood ; Spike Glycoprotein, Coronavirus/immunology ; Coronavirus Nucleocapsid Proteins ; Phosphoproteins ; },
abstract = {BACKGROUND: Post-COVID condition (PCC), or long COVID, affects a significant proportion of individuals following SARS-CoV-2 infection, yet its molecular framework remains poorly understood. This study aimed to define the molecular profile of PCC by integrating broad proteomic analysis using Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) with targeted antigen quantification through targeted mass spectrometry (MRM/SRM).<br><br>METHODS: Plasma and pellet fractions from 65 PCC patients, classified as symptomatic or asymptomatic, were analyzed using SWATH-MS with updated SARS-CoV-2 protein libraries (v2022 and v2024), enabling a comprehensive profiling of immune- and viral-related proteins. The presence of viral antigens, specifically spike and nucleocapsid proteins, was quantified using MRM/SRM. A protein-concentration-based severity metric using clustering analysis and dimensionality reduction methods was proposed to assess correlations between proteomic alterations and clinical symptoms.<br><br>RESULTS: A key finding in PCC patients, particularly in symptomatic cases, was a pronounced downregulation of immunoglobulins, including kappa and lambda light chains. SWATH-MS analysis identified six proteins (corresponding to UniProt entries Q8N5F4, LV147, KV311, KVD20, A0A5C2G1U0, and KV315) that strongly correlated with disease severity (R&#xb2; > 0.9), highlighting their potential as biomarkers. In pellet samples, the protein G1SG72 (ABCE1) emerged as a marker associated with severity, suggesting possible alterations in antiviral responses. The severity metric proposed showed a strong correlation with clinical symptoms, providing a quantifiable measure of PCC severity and enabling effective patient stratification. Additionally, MRM/SRM analysis detected the persistent presence of SARS-CoV-2 antigens, specifically the Spike and Nucleocapsid proteins, in symptomatic PCC patients.<br><br>CONCLUSIONS: This study defines a molecular profile of PCC, marked by immunoglobulin downregulation and the persistence of SARS-CoV-2 antigens, which may contribute to ongoing immune alterations in PCC. The severity metric derived from proteomic profiling provides a tool for categorizing PCC patients based on symptom severity and could support future studies aimed at targeted interventions.},
}
@article {pmid40618224,
year = {2025},
author = {Willis, MC and Hansen, DJ},
title = {Commentary: Psychosocial features of pediatric long COVID and the challenges of considering temporal and environmental context during a pandemic.},
journal = {Journal of pediatric psychology},
volume = {50},
number = {10},
pages = {927-929},
doi = {10.1093/jpepsy/jsaf052},
pmid = {40618224},
issn = {1465-735X},
}
@article {pmid40615692,
year = {2025},
author = {Hong, C and Wen, J and Zhang, HG and Ayakulangara Panickan, V and Yang, DY and Chen, AW and Xiong, X and Wang, X and Morris, M and Morini, S and Sangar, R and Dey, A and Samayamuthu, MJ and Liao, K and Bonzel, CL and Tanukonda, V and Maripuri, M and Honerlaw, J and Ho, YL and Visweswaran, S and Kohane, IS and Cho, K and Brat, G and Xia, Z and Cai, T},
title = {Label efficient phenotyping for Long COVID using electronic health records.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {405},
pmid = {40615692},
issn = {2398-6352},
support = {R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; },
abstract = {Long COVID poses a significant disease burden globally, but its heterogeneous presentation and unreliable coding practices render it difficult to study. Developing efficient phenotyping algorithms is crucial to enabling risk prediction and effective management of Long COVID. We introduce the LAbel-efficienT Long COVID pHenotyping (LATCH) algorithm, which synthesizes a small number of gold-standard labels and a large, unlabeled dataset with many electronic health record (EHR) features. Both internal validation and external validation demonstrated the superior performance of LATCH over methods using the U09.9 Long COVID EHR code alone. Our downstream analysis revealed a pattern of elevated healthcare utilization due to Long COVID, peaking at and continuing beyond the fourth month following COVID infection. LATCH enhances the classification of Long COVID by fully utilizing both labeled and unlabeled data, providing vital insights into healthcare utilization trends, informing clinical and public health responses to the enduring consequences of COVID-19.},
}
@article {pmid40614661,
year = {2025},
author = {Soares Pereira, LM and de Souza E Souza, I and Dos Santos Brito, WR and Dos Santos, EF and da Costa, FP and Lima de Sarges, KM and Damasceno Cantanhede, MH and de Brito, MTFM and da Silva, ALS and de Meira Leite, M and de Almeida Viana, MNDS and Barbosa Rodrigues, FB and da Silva, R and Rachid Viana, GM and do Socorro Souza Chaves, T and de Oliveira Lameira Veríssimo, A and da Silva Carvalho, M and Henriques, DF and da Silva, CP and Lima Nunes, JA and Costa, IB and Vieira Cayres-Vallinoto, IM and Brasil-Costa, I and Simões Quaresma, JA and Monteiro Rangel da Silva, AN and Freitas Queiroz, MA and Dos Santos, EJM and Magno Falcão, LF and Rosário Vallinoto, AC},
title = {Gene expression profile of immune response markers associated with long COVID and its clinical aspects in a cohort from northern Brazil.},
journal = {Human immunology},
volume = {86},
number = {4},
pages = {111341},
doi = {10.1016/j.humimm.2025.111341},
pmid = {40614661},
issn = {1879-1166},
mesh = {Humans ; *COVID-19/genetics/immunology ; Female ; Brazil ; Male ; Middle Aged ; Adult ; *SARS-CoV-2/immunology ; Biomarkers/metabolism ; Aged ; *Transcriptome ; Cohort Studies ; Interferon Regulatory Factor-3/genetics ; Gene Expression Profiling ; Interferon Regulatory Factor-7/genetics ; },
abstract = {BACKGROUND: Long COVID is characterized by a multisystemic, and complex disease and current efforts are focused on the search for biomarkers associated with clinical outcomes.<br><br>OBJECTIVE: In this study, we evaluated the gene expression of 15 biomarkers and their relationship with the clinical aspects of the condition.<br><br>METHODS: c-DNA samples from 15 patients with long COVID, 15 patients recovered and without sequelae (RWS), and 15 patients with symptomatic acute COVID-19 were analyzed. The relative expression of genes was determined by the 2-&#x394;&#x394;CT method from real-time PCR. Sociodemographic and clinical data of interest were extracted from medical records.<br><br>RESULTS: Of the 15 biomarkers, only the expression of TREX1, FOXP3, MYD88 and FASL was not associated with long COVID. The genes IRF7, IRF3, and IFI16 performed best as biomarkers of long COVID (AUC&#xa0;&#x2265;&#xa0;0.90, p&#xa0;&#x2264;&#xa0;0.05). Except for MDA5 and RIG-1 genes, the expression of the other eight genes was associated with the presence of comorbidities, medication use, and complaints of fever, abdominal pain, eye pain, and headache (H&#xa0;>&#xa0;9.0; p&#xa0;&#x2264;&#xa0;0.05). IRF3 expression was specifically associated with long COVID when compared to acute COVID (med.: 41.2; IQR: 116.20; p: 0.0036).<br><br>CONCLUSION: Our results suggest that classical immune response genes are upregulated in long COVID and that certain clinical aspects of the disease may influence the expression profile of the studied genes.},
}
@article {pmid40612098,
year = {2025},
author = {Martin, S and Janse Van Rensburg, M and Le, HT and Firth, C and Chandrasekar, A and Clark, SE and Vanderslott, S and Vindrola-Padros, C and Vera San Juan, N},
title = {LISTEN: lived experiences of Long COVID: a social media analysis of mental health and supplement use.},
journal = {Frontiers in big data},
volume = {8},
number = {},
pages = {1539724},
pmid = {40612098},
issn = {2624-909X},
abstract = {INTRODUCTION: Long COVID, or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is a complex condition characterized by a wide range of persistent symptoms that can significantly impact an individual's quality of life and mental health. This study explores public perspectives on the mental health impact of Long COVID and the use of dietary supplements for recovery, drawing on social media content. It uniquely addresses how individuals with Long COVID discuss supplement use in the absence of public health recommendations.<br><br>METHODS: The study employs the LISTEN method ("Collaborative and Digital Analysis of Big Qual Data in Time Sensitive Contexts"), an interdisciplinary approach that combines human insight and digital analysis software. Social media data related to Long COVID, mental health, and supplement use were collected using the Pulsar Platform. Data were analyzed using the free-text discourse analysis tool Infranodus and collaborative qualitative analysis methods.<br><br>RESULTS: The findings reveal key themes, including the impact of Long COVID on mental health, occupational health, and the use of food supplements. Analysis of attitudes toward supplement use highlights the prevalence of negative emotions and experiences among Long COVID patients. The study also identifies the need for evidence-based recommendations and patient education regarding supplement use.<br><br>DISCUSSION: The findings contribute to a better understanding of the complex nature of Long COVID and inform the development of comprehensive, patient-centered care strategies addressing both physical and mental health needs.},
}
@article {pmid40610519,
year = {2025},
author = {Yukari Magawa, J and Jacintho, LC and Alves Ferreira, M and Ramos Oliveira, J and Rahal Guaragna Machado, R and Kuramoto Takara, A and Moreno Lima de Oliveira, R and Cesario Lima, A and Sasahara, GL and Lopes Adami, F and Xavier Medeiros, G and de Souza Apostolico, J and Ruz Fernandes, E and Bruna Leal de Oliveira, D and Durigon, EL and Giavina Bianchi, P and Boscardin, SB and Santoro Rosa, D and Cunha-Neto, E and Kalil, J and Coelho, V and Souza Santos, K},
title = {Protective role of anti-SARS-CoV-2 antibody responses against vital organ related long COVID symptoms.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {23705},
pmid = {40610519},
issn = {2045-2322},
support = {001 (JO, JM, and AU)//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001 (JO, JM, and AU)//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001 (JO, JM, and AU)//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001 (JO, JM, and AU)//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001 (JO, JM, and AU)//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001 (JO, JM, and AU)//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 408771/2022-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 408771/2022-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 408771/2022-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 408771/2022-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 2020/05256-7, 2017/24769-2, 2016/20045-7 and 2020/06409-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2020/05256-7, 2017/24769-2, 2016/20045-7 and 2020/06409-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2020/05256-7, 2017/24769-2, 2016/20045-7 and 2020/06409-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2020/05256-7, 2017/24769-2, 2016/20045-7 and 2020/06409-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2020/05256-7, 2017/24769-2, 2016/20045-7 and 2020/06409-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2020/05256-7, 2017/24769-2, 2016/20045-7 and 2020/06409-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 01.20.0009.00//Financiadora de Estudos e Projetos/ ; 01.20.0009.00//Financiadora de Estudos e Projetos/ ; 01.20.0009.00//Financiadora de Estudos e Projetos/ ; 01.20.0009.00//Financiadora de Estudos e Projetos/ ; 01.20.0009.00//Financiadora de Estudos e Projetos/ ; 01.20.0009.00//Financiadora de Estudos e Projetos/ ; },
mesh = {Humans ; *COVID-19/immunology/epidemiology/complications/virology ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology/blood ; Male ; Female ; Middle Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; },
abstract = {COVID-19 pandemic continues to challenge the world with a major public health problem, long COVID (LC), which is estimated to affect over 400 million people worldwide. Many unknowns remain regarding the mechanisms involved in LC. We investigated the impact of anti-SARS-CoV-2 antibody and IFN-γ responses on the development of LC and its various phenotypes. We studied a cohort of 137 convalescents following predominantly mild COVID-19 during the first pandemic wave (2020) and up to one-year post-infection. We found 45% of LC cases that were associated with a greater number and duration of acute-phase symptoms. Cardiovascular and/or gastrointestinal symptoms in the acute phase were associated to protection against LC development, while pulmonary, otorhinolaryngological, musculoskeletal and other symptoms were associated with increased risk of LC development. Regarding LC phenotypes, we observed risk associations and potentially deleterious effects of anti-SARS-CoV-2 antibodies for LC symptoms classified as general or other. In contrast, for vital organ-related LC symptoms, we found only protective associations, particularly for cardiovascular symptoms, which indeed had a low prevalence in LC (16%). Collectively, our data suggest that anti-SARS-CoV-2 antibodies play a protective role against vital organ-related LC symptoms, especially cardiovascular symptoms, but are insufficient in preventing or limiting other highly prevalent LC symptoms, such as neurological, psychiatric and pulmonary.},
}
@article {pmid40609301,
year = {2025},
author = {Lebrun, H and Zablith, I and Stone, J and Vasilache, A and Gouraud, C and Ancellin-Geay, A and Kachaner, A and Ranque, B and Lemogne, C and Pitron, V},
title = {Comparing labels for persistent physical symptoms: A cross-sectional study among lay participants and healthcare professionals.},
journal = {Journal of psychosomatic research},
volume = {195},
number = {},
pages = {112197},
doi = {10.1016/j.jpsychores.2025.112197},
pmid = {40609301},
issn = {1879-1360},
mesh = {Humans ; Female ; Male ; Adult ; Cross-Sectional Studies ; *Health Personnel/psychology ; Middle Aged ; Surveys and Questionnaires ; *Medically Unexplained Symptoms ; *Somatoform Disorders/diagnosis/psychology ; COVID-19 ; },
abstract = {CONTEXT: Numerous labels are used to describe physical symptoms that remain for at least several months and cause significant distress (i.e., persistent physical symptoms, PPS). This study aims to assess attitudes associated with various labels among lay participants and healthcare professionals.<br><br>METHODS: Participants recruited via mailing lists of volunteers completed an online questionnaire assessing their views on underlying physical and mental causations for ten diagnostic labels accounting for PPS. Lay participants rated their feelings of offence associated with each label, and healthcare professionals their willingness to take care of a patient diagnosed with each label. Mixed regression models investigated the factors associated with feelings of offence and willingness to care.<br><br>RESULTS: 266 lay participants (mean age: 43; 70&#xa0;% women) and 126 healthcare professionals (mean age: 42; 69&#xa0;% women) were included. Labels rated high on perceived mental causation tended to be rated low on physical causation and vice versa in both populations, although this effect was stronger in lay participants. "Long COVID", "persistent physical symptoms" and "functional symptoms" were rated with higher physical causation by lay participants compared to health professionals (p&#xa0;<&#xa0;0.001), whereas "somatic symptom disorder" and "psychosomatic" were rated with higher mental causation. Regression models showed that perceived mental causation was associated with feelings of offence in lay participants, while perceived physical causation was associated with less offence. Perceived physical causation was associated with willingness to care among healthcare professionals.<br><br>DISCUSSION: Some diagnostic labels provoke negative attitudes, both among lay participants and healthcare professionals, probably hindering clinician/patient relationships and treatment.},
}
@article {pmid40609105,
year = {2025},
author = {Bustos-Viviescas, BJ and García-Yerena, CE and García-Galviz, JA},
title = {Myopathy, fatigue and long COVID-19: considerations of the new neuromuscular histopathology.},
journal = {Cirugia y cirujanos},
volume = {93},
number = {3},
pages = {337-338},
doi = {10.24875/CIRU.23000429},
pmid = {40609105},
issn = {2444-054X},
}
@article {pmid40608708,
year = {2025},
author = {Xu, Y and Yuan, Z and Li, J and Liu, W and Liu, L},
title = {A survey on the situation and risk factors of secondary infection after the second wave of the Omicron COVID-19 in China.},
journal = {Journal of infection in developing countries},
volume = {19},
number = {6},
pages = {812-820},
doi = {10.3855/jidc.20927},
pmid = {40608708},
issn = {1972-2680},
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Male ; Female ; China/epidemiology ; Adult ; Risk Factors ; *Reinfection/epidemiology ; Middle Aged ; SARS-CoV-2 ; COVID-19 Vaccines/administration &amp; dosage ; Surveys and Questionnaires ; Health Personnel/statistics &amp; numerical data ; Vaccination/statistics &amp; numerical data ; Young Adult ; },
abstract = {INTRODUCTION: Reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been occurring more frequently. Healthcare workers are among the most at-risk groups due to their direct exposure to SARS-CoV-2 while providing medical care. We aimed to understand the potential factors that affect reinfection.<br><br>METHODOLOGY: 1399 healthy workers at the General Hospital of Central Theater Command were enrolled for an online questionnaire from 27 June to 10 July 2023. The selected individuals were divided into the primary infection group and the secondary infection group based on the number of SARS-CoV-2 infections.<br><br>RESULTS: About 95% of the total population had been vaccinated. A higher proportion of the primary group had received 3 doses of vaccines and inactivated vaccines, than the secondary group (p < 0.001). The symptoms, duration, and severity of the majority of participants significantly decreased during secondary infection, compared to primary infection. After adjusting for factors such as gender, age, vaccine dose, and vaccine type; multiple regression analysis indicated that the patients with disease duration > 7 days or long coronavirus disease 2019 (long COVID-19) history during primary infection had a higher risk of secondary infection with Omicron (odds ratio, OR = 2.2, p < 0.001; OR = 2.4, p < 0.001).<br><br>CONCLUSIONS: The patients with history of long COVID-19 or longer duration of disease after primary infection had a higher risk of Omicron reinfection. This study identified the clinical manifestations during Omicron primary and secondary infection; and the potential factors that may influence reinfection.},
}
@article {pmid40607414,
year = {2025},
author = {Abooali, M and Yasinska, IM and Thapa, G and Lei, X and da Costa, KAS and Schlichtner, S and Berger, SM and Fasler-Kan, E and Temperton, NJ and Vuono, R and Sumbayev, VV},
title = {Wuhan strain of SARS-CoV-2 triggers activation of immune evasion machinery similar to the one operated by cancer cells.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1599352},
pmid = {40607414},
issn = {1664-3224},
mesh = {Humans ; *SARS-CoV-2/immunology ; *COVID-19/immunology/virology ; *Immune Evasion/immunology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Epithelial Cells/immunology/virology ; Cell Line ; B7-H1 Antigen/metabolism ; *Neoplasms/immunology ; Ketoglutaric Acids/metabolism ; },
abstract = {In the last 2 years, there has been an increasing concern that SARS-CoV-2 infection may represent a marker of undiagnosed cancers. A potential connection between COVID-19/long COVID and malignant transformation/cancer progression was reported in a number of studies. It is, however, unclear if the virus itself can cause malignant transformation or if it has a potential to support malignant processes in human body. We analyzed nasopharyngeal swabs collected from individuals infected with Wuhan strain of SARS-CoV-2 and conducted in vitro studies using BEAS-2B human bronchial epithelial cells. Here we report that Wuhan strain of SARS-CoV-2 and its spike protein induce activation of hypoxia-inducible factor 1 (HIF-1) transcription complex in infected cells. This effect is achieved through conversion of cellular 2-oxoglutarate into 2-hydroxy-glutarate, which most likely blocks the activity of HIF-1α prolyl hydroxylation. As such, it leads to activation of HIF-1, which triggers production of transforming growth factor-β type 1 (TGF-β). TGF-β induces expression of immune checkpoint proteins, such as galectin-9, programmed death-ligand 1, and indoleamine-2,3-dioxygenase, an enzyme, which is involved in production of immunosuppressive amino acid called L-kynurenine. These immune checkpoint pathways were capable of suppressing both helper and cytotoxic activities of T lymphocytes and, as such, could potentially support malignant processes in infected tissues.},
}
@article {pmid40607062,
year = {2025},
author = {García-López, DA and Monárrez-Espino, J and Borrego-Moreno, JC and Zheng, J and Mandal, R and Torres-Calzada, C and Oropeza-Valdez, JJ and Tenório Nunes, A and Sánchez Rodríguez, SH and López, JA and Calzada Rodríguez, BE and Wishart, DS and López-Hernández, Y},
title = {Comprehensive clinical and metabolomics profiling of COVID-19 Mexican patients across three epidemiological waves.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1607583},
pmid = {40607062},
issn = {2296-889X},
abstract = {INTRODUCTION: As of mid-2024, COVID-19 has affected over 676 million people worldwide, leading to more than 6.8 million deaths. Numerous studies have documented metabolic changes occurring during both the acute phase of the disease and the recovery phase, which, in some cases, contribute to the development of long COVID syndrome.<br><br>AIMS AND METHODS: In this study, we aimed to evaluate clinical, laboratory, and comprehensive metabolomic data from hospitalized COVID-19 patients during the second, third and fourth waves (Alpha, Delta, and Omicron). A targeted, fully quantitative metabolomics assay (TMIC MEGA Assay) was used to measure 529 metabolites and lipids in plasma samples. The metabolomic profiles of these patients were compared according to different and relevant factors impacting COVID-19 outcome, such as age, sex, comorbidities, and vaccination status.<br><br>RESULTS: Among the 21 classes of compounds evaluated in this study, amino acids and lipids were the most dysregulated when comparing age, sex, comorbidities, vaccination status, and the different epidemiological waves. This is the most comprehensive analysis in Mexico providing absolute quantitative data for 529 metabolites and lipids measured in hospitalized COVID-19 patients, which could be used to monitor their metabolic status and clinical outcomes associated with COVID-19 infection or with long COVID syndrome.},
}
@article {pmid40604227,
year = {2025},
author = {Noij, LCE and Lap, CR and Luijten, MAJ and Hashimoto, S and Teela, L and Oostrom, KJ and Alsem, MW and van Houten, MA and Biesbroek, G and Haverman, L and Maitland-van der Zee, AH and van Goudoever, JB and Terheggen-Lagro, SWJ},
title = {Quality of life and mental health in children with long COVID.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {271},
pmid = {40604227},
issn = {2730-664X},
abstract = {BACKGROUND: Pediatric Long COVID (PLC) is a heterogeneous condition, which can have a substantial impact on daily life of children and adolescents. This study aimed to evaluate health related quality of life (HRQoL), and mental and social health of children with PLC, in relation to children with other chronic health conditions (CHC) and from the general population (GP) during the pandemic.<br><br>METHODS: Dutch children (8-18 years) with PLC (n&#x2009;=&#x2009;106, 31% male) were included between May 2021 and March 2023. Reference data was available from a CHC-cohort (n&#x2009;=&#x2009;90, 56% male) and GP-cohort (n&#x2009;=&#x2009;844, 47% male) during the first wave of the pandemic (April-May, 2020). Participants completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 and Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (Anxiety, Anger, Depressive symptoms, Sleep-Related Impairment (SRI), and Peer Relationships). Mean scores were analyzed using adjusted ANCOVA. Relative risks (RR (95% CI)) were calculated for impaired HRQoL and severe PROMIS scores.<br><br>RESULTS: Children with PLC report high proportions of impaired HRQoL (84%, RR&#x2009;=&#x2009;3.67 (2.35-5.74)), and have significantly lower PedsQL scores than children with CHC. Children with PLC also exhibit worse PROMIS T-scores of Anxiety, Depressive Symptoms, and SRI than children from the CHC- and GP-cohorts (mean difference range 2.2-9.8 (95%CI 0.6-11.7)), and significantly higher risks of severe anxiety (17%), depressive symptoms (18%), and SRI (17%).<br><br>CONCLUSIONS: PLC can severely impact HRQoL and mental and social health in children. Screening of these outcomes and individualized management of children with PLC should be a vital part of clinical care for these highly burdened patients.},
}
@article {pmid40602071,
year = {2025},
author = {Heald, A and Williams, R and Khan, Z and Mudaliar, R and Khan, A and Naseem, A and Stewart, S and Bakerly, ND and Ollier, W},
title = {The predisposing factors to having a coded diagnosis of Long COVID.},
journal = {Public health},
volume = {246},
number = {},
pages = {105826},
doi = {10.1016/j.puhe.2025.105826},
pmid = {40602071},
issn = {1476-5616},
mesh = {Humans ; *COVID-19/epidemiology/diagnosis/mortality ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Adult ; SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; },
abstract = {OBJECTIVES: Long COVID is characterized by a constellation of persistent symptoms following an initial infection with COVID-19 virus. The primary focus of this study was to investigate how the characteristics of people diagnosed with Long COVID differed from those of matched individuals who did not have a diagnosis of Long COVID, after at least one confirmed positive COVID-19 test.<br><br>STUDY DESIGN: A retrospective observational cohort study was performed using data collected for the time period, January 1, 2020 to January 31, 2024 from a population database of 2.85 million people.<br><br>METHODS: The primary outcome was a primary care coded diagnosis, or referral for treatment of Long COVID following an acute COVID-19 infection, to a Long COVID clinic. Twenty six thousand, six hundred and twenty six (26,626) individuals were identified with a diagnosis of Long COVID and at least one previous recorded COVID-19 positive test. These were matched by age and sex with 133,165 individuals (i.e. an approximate ratio of 5 controls to one case) with at least one previous recorded COVID-19 positive test but no recorded diagnosis of Long COVID. Mortality rate was also analysed in relation to having a previous confirmed acute COVID-19 infection.<br><br>RESULTS: There was a higher proportion of people with 2, 3, 4 and 5 or more comorbidities in the diagnosed Long COVID group compared to those with one or no comorbidity. Black/ Black British ethnicity (+28&#xa0;%) and Mixed ethnicity (+37&#xa0;%) were both associated with a higher likelihood of a Long COVID diagnosis when compared to White ethnicity. Those in the most disadvantaged quintile (as measured by Townsend index) were more than twice as likely to have Long COVID than the most advantaged quintile. The risk of Long COVID increased by 5.7&#xa0;% per each comorbidity, with modulation by the number of COVID-19 vaccinations. The risk of Long COVID doubled for every additional confirmed positive COVID-19 test. BMI did not have an effect when account was taken of Townsend quintile. Lastly, we analysed mortality rates following a COVID-19 infection. Female sex was associated with a lower risk of death. More disadvantaged individuals as measured by Townsend quintile were more likely to have died. This risk was nearly doubled for the most deprived quintile compared to least deprived quintile.<br><br>CONCLUSIONS: In this city region wide study with individuals matched for age and sex, we have determined that being in a socially disadvantaged situation and being Black/Black British or of Mixed ethnicity increased the risk of developing Long COVID. BMI did not have an effect when account was taken of Townsend quintile. These findings can inform public health messages and public health interventions going forward, whether in relation to Long COVID or future pandemic preparedness.},
}
@article {pmid40600494,
year = {2025},
author = {Mir, G and Mullard, J and Parkin, A and Lee, C and Clarke, J and De Kock, JH and Prociuk, D and Darbyshire, JL and Evans, S and Sivan, M and , },
title = {Addressing Inequalities in Long Covid Healthcare: A Mixed-Methods Study on Building Inclusive Services.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70336},
pmid = {40600494},
issn = {1369-7625},
support = {//This study is independent research funded by the National Institute for Health and Care Research (NIHR) (long Covid grant, Ref: COV-LT2-0016)./ ; },
mesh = {Humans ; *Healthcare Disparities ; *COVID-19/therapy/epidemiology ; Female ; Male ; Qualitative Research ; Adult ; Middle Aged ; Primary Health Care ; Health Services Accessibility ; Interviews as Topic ; London ; Vulnerable Populations ; England ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: Long Covid (LC) significantly impacts health, economic and social activities. Women, deprived, learning disability, homeless and some minority ethnic populations have high prevalence rates but low access to support, indicating health inequities in LC care.<br><br>AIM: To identify health inequities in LC care and inclusion strategies that align with the priorities of people with LC.<br><br>DESIGN AND SETTING: Mixed-methods study employing qualitative data from people with LC, professional experts, LC clinic staff and primary care data from North West (NW) London GPs.<br><br>METHOD: Qualitative interviews with 23 people with LC and 18 professional experts explored the experience of diagnosis and support for people from disadvantaged groups. Framework analysis identified themes that informed the subsequent collection of clinic and primary care data. Staff from 10 LC clinics across England provided survey and qualitative data describing their initiatives to identify and reduce inequalities. Descriptive quantitative analysis of NW London adult primary care records (n&#x2009;=&#x2009;6078), linked to hospital use across England, explored LC diagnosis and care pathways for diverse groups of people with LC.<br><br>RESULTS: Study participants from disadvantaged groups reported delays in formal diagnosis and specialist referrals being initated&#xa0;and had low trust in healthcare services. They described difficulties in obtaining information, advice and support as barriers to access specialist referrals. LC clinics confirmed the under-referral of those from the most disadvantaged groups compared to the general population. Primary care data confirmed under-referral of people with LC to specialist clinics; however, incomplete data across the LC clinical pathway prevented an analysis of equity in referral patterns between population groups. Clinics used various strategies to improve access and increase the flow of disadvantaged groups from primary care to LC services. Interventions included data collection to identify underserved groups, targeting outreach to primary care and community providers, adapting clinic provision and developing care pathways involving multidisciplinary teams (MDTs), primary and secondary care practitioners and third sector organisations. These activities were not widespread, however, and were particular to a few clinics.<br><br>CONCLUSION: Strategies to improve access to LC healthcare provide a starting point to explore inclusive care pathways for people with LC from disadvantaged social groups. Future research should focus on the effectiveness of initiatives to increase access to specialist LC provision among disadvantaged groups and establish greater trust in healthcare providers.<br><br>This study highlights the need for health system practitioners to identify under-represented groups and target inclusion initiatives at these populations in sensitive and appropriate ways. Improved diagnosis and support for such populations would be helped by training health and social care practitioners to recognise and accept the accounts of people with LC about their symptoms. Protocols that support consistent practice in referrals for specialist care are also needed. People with LC from disadvantaged groups often lack access to evidence-based sources of advice and information. Practitioners should provide information on LC while individuals are waiting to receive specialist care and should advocate for support from employers, including work modifications.<br><br>People with lived experience of LC were involved in the study as members of the research team and LOCOMOTION Patient Advisory Group (PAG). The PAG was involved in the wider study design, including the initial grant application, attending proposal planning meetings and helping to develop the research aim, objectives and questions. During the course of the study, the PAG met quarterly with each other and at least monthly with other research team members to review progress and feed into data collection and analysis processes. PAG members also attended a Quality Improvement Collaborative meeting involving academics and LC practitioners, which discussed initial findings from data analysis of qualitative interviews on LC inequalities. Through these meetings, the group supported and oversaw the study as a whole in terms of how data was collected, recruitment of participants, involvement in data analysis and interpretation, as well as providing more specific advice to all the individual workstreams within the study. A PPI facilitator within the study team provided training and support to PAG members in these areas and was available to respond to other needs expressed by the group. PAG members have also been involved in organising and contributing to a wide range of study dissemination events. PAG involvement throughout the study has ensured that the research is aligned with the key research priorities of people diagnosed with LC as well as those with LC symptoms but no formal diagnosis. PAG members were recruited through and linked to the LC clinics involved in the study and have helped disseminate study findings to local clinical practice, the lay public and other LC centres with which they are involved. S.E. is a PAG member from a minority ethnic background and a co-author on the paper. She has been involved in overseeing and supporting data collection and interpretation relating to inequalities affecting people with LC and has contributed to the preparation of this manuscript from an early draft to production of the final version.},
}
@article {pmid40599534,
year = {2025},
author = {Sorets, TR and Finley, JA and LaFrance, WC and Patten, RV and Mordecai, K and Jimenez, M and Suchy, S and Cahan, J and Koralnik, IJ and Cherney, LR and Cotton, E},
title = {Beyond mood screening: a pilot study of emotional, cognitive, and somatic concerns in patients with Long COVID.},
journal = {Frontiers in psychology},
volume = {16},
number = {},
pages = {1517299},
pmid = {40599534},
issn = {1664-1078},
abstract = {OBJECTIVE: This descriptive pilot study reported the emotional, cognitive, and somatic concerns of a clinically referred sample of patients with Long COVID using a comprehensive psychological measure. These subjective concerns were considered in the context of other psychological characteristics and historical mental health factors.<br><br>METHODS: The study sample comprised 26 adults with Long COVID who were referred from a neurology COVID-19 clinic for neuropsychological screening based on the patient's cognitive concerns. Empirically established cutoffs from the Personality Assessment Inventory were used to assess clinically elevated emotional, cognitive, and somatic concerns. Preexisting mental health data were obtained via medical records and clinical interview.<br><br>RESULTS: Approximately 62 and 50% of the sample had elevated somatic and cognitive concerns, respectively. Additionally, 42% of the sample exhibited elevated emotional concerns associated with depression, but this was primarily driven by the physiological aspects of depression. Between 15-27% of patients had elevated anxiety-related concerns. Over 80% of the sample had previously received psychotherapy and had been diagnosed with a mental health disorder prior to their SARS-CoV-2 infection. Furthermore, over half of the sample reported a history of abuse, and 12-15% had previously attempted suicide or had been hospitalized for psychiatric reasons.<br><br>CONCLUSIONS: Findings suggest that patients with Long COVID may present with extensive psychiatric histories and various somatic, cognitive, and emotional concerns. These psychological characteristics may be important for the treatment of Long COVID but may be overlooked using screening measures.},
}
@article {pmid40599143,
year = {2025},
author = {Lespezeanu, DA and Ungureanu, FD and Circiumariu, B and Constantin, C and Serafinceanu, C and Radu, FI and Kraft, A and Bacalbasa, N},
title = {Control of type 2 diabetes in patients with cancer and chronic pro-inflammatory cytokines during the COVID-19 pandemic.},
journal = {Journal of medicine and life},
volume = {18},
number = {5},
pages = {428-439},
pmid = {40599143},
issn = {1844-3117},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus, Type 2/drug therapy/complications ; *Neoplasms/complications ; Male ; Female ; Middle Aged ; Interleukin 1 Receptor Antagonist Protein/therapeutic use/administration &amp; dosage ; Aged ; SARS-CoV-2 ; Retrospective Studies ; *Cytokines/blood ; Sulfonylurea Compounds/therapeutic use/administration &amp; dosage ; Hypoglycemic Agents/therapeutic use/administration &amp; dosage ; Azithromycin/therapeutic use/administration &amp; dosage ; COVID-19 Drug Treatment ; Adult ; },
abstract = {Patients with cancer and severe COVID-19 pneumonia treated with injectable azithromycin and anakinra frequently develop dysglycemia, necessitating initiation of sulfonylurea therapy (gliquidone or glimepiride). We retrospectively reviewed adults (≥30 years) with diabetes and cancer who were hospitalised for COVID-19 at the Central Military Hospital Bucharest and the Matei Bals National Institute between March 2020 and August 2022. All patients completed a 14-day course of azithromycin + anakinra and survived to discharge. Glycaemic control was achieved with fixed-dose gliquidone 30 mg or glimepiride 2, 3, or 6 mg, chosen according to each patient's inflammatory-cardiac profile. Central insulin resistance may lead to the risk of cardiometabolic syndrome through the increase of inflammatory markers (TNF-alpha and PAI-1), treated with gliquidone, in 50 patients with cancer infected with COVID-19, who were dependent on developing immunothrombosis. Peripheral insulin resistance leads to the risk of cardiovascular events through the increase of inflammatory markers, IL-6 and Il-1, treated with glimepiride, in 50 patients with cancer infected with COVID-19.},
}
@article {pmid40598822,
year = {2025},
author = {Kvernebo, K and Liv Kristin Wikslund, L and Drezek, K and Jaramillo, A and Capone, L and Helmy, M and Zhao, Y and Aguirre, A and D'Alessandro, D},
title = {COVID-19 Patients Have Peripheral Microvascular Dysfunction and Tissue Hypoxia in Spite of Successful Treatment of Lung Failure: A Proof of Concept Study.},
journal = {Microcirculation (New York, N.Y. : 1994)},
volume = {32},
number = {5},
pages = {e70014},
doi = {10.1111/micc.70014},
pmid = {40598822},
issn = {1549-8719},
mesh = {Humans ; *COVID-19/physiopathology/complications/therapy/blood ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; Aged ; *Microcirculation ; *Hypoxia/physiopathology/etiology ; Oxygen Saturation ; Oxygen/metabolism/blood ; Proof of Concept Study ; Adult ; Microvessels/physiopathology ; *Respiratory Insufficiency/therapy/etiology ; },
abstract = {BACKGROUND: Availability of oxygen (O2) is essential for life and function of all cells of the human body (n ≈ 10[13]-10[14] cells). COVID-19 patients often have impaired lung function with compromised oxygen uptake, but little is known about microvascular oxygen delivery and tissue oxygenation.<br><br>OBJECTIVES: Use the Oxygen Delivery Index (ODIN) concept to assess peripheral microvascular regulation and oxygen extraction in COVID-19 patients.<br><br>METHODS: The ODIN concept includes two technologies (diffuse reflectance spectroscopy-DRS and computer assisted microscopy-CAM) for data acquisition from subepidermal nutritive capillaries. Output parameters are microvascular oxygen saturation (SmvO2) and functional capillary density (FCD).<br><br>RESULTS: Forty patients hospitalized for COVID-19 grouped into early discharge (<&#x2009;7&#x2009;days, n&#x2009;=&#x2009;11), severe (beyond 7&#x2009;days, n&#x2009;=&#x2009;24) and non-survivors (n&#x2009;=&#x2009;5), and healthy controls (n&#x2009;=&#x2009;23) were examined. Microvascular oxygen saturation (SmvO2) and the corresponding O2 extraction (SaO2-SmvO2) was 56%&#x2009;&#xb1;&#x2009;4%/42%&#x2009;&#xb1;&#x2009;9% (mean&#x2009;&#xb1;&#x2009;SD) in healthy controls (n&#x2009;=&#x2009;11), 61&#x2009;&#xb1;&#x2009;10/37&#x2009;&#xb1;&#x2009;10 for historic controls (n&#x2009;=&#x2009;12), significantly different (p&#x2009;<&#x2009;0.01) as compared with all COVID-19 groups (early discharge: 40%&#x2009;&#xb1;&#x2009;13%/54%&#x2009;&#xb1;&#x2009;13%, severe: 34%&#x2009;&#xb1;&#x2009;15%/60%&#x2009;&#xb1;&#x2009;15%, non-survivors 22%&#x2009;&#xb1;&#x2009;15%/73%&#x2009;&#xb1;&#x2009;16%). FCD expressed as the relative number of red pixels (belonging to a capillary erythrocyte) in a CAM frame were reduced in alle patient groups as compared to historic controls (p&#x2009;<&#x2009;0&#x22c5;05).<br><br>CONCLUSION: Results show skin microvascular dysregulation and tissue hypoxia in patients, indicative of hypoxia also in other tissues. We hypothesize that tissue hypoxia is a cause of reversible and non-reversible long COVID-19 symptoms and of mortality.},
}
@article {pmid40597822,
year = {2025},
author = {Münte, C and Glattacker, M and Müller, S and Zülke, AE and Heinze, M and Riedel-Heller, SG and Pieper, D and Jacke, C and Deckert, S and Neumann, A},
title = {Long COVID in people with mental health disorders: a scoping review.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {669},
pmid = {40597822},
issn = {1471-244X},
mesh = {Humans ; *COVID-19/complications/psychology ; *Mental Disorders/psychology/epidemiology/complications/therapy ; *Post-Acute COVID-19 Syndrome/complications/epidemiology/psychology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID, Post COVID Syndrome or PASC (post-acute sequelae of COVID-19), according to the World Health Organization (WHO), is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. The term Long COVID will be used throughout this review. Little is known about individuals with pre-existing mental health conditions experiencing Long COVID. This scoping review aims to provide an overview of these individuals, focusing on: 1) the course of mental disorders, 2) care needs, 3) utilization of healthcare services, and 4) psychosocial aspects, as outlined by the International Classification of Functioning (ICF).<br><br>METHODS: This review followed the JBI (Joanna Briggs Institute) methodology for scoping reviews and the PRISMA extension for scoping reviews. We included reports focusing on individuals with at least one pre-existing mental health diagnosis and Long COVID. Full-text reports in English or German were included, with no geographical limitations. Literature searches were conducted in PubMed, Embase, and PsycINFO on November 1, 2023, for records published between January 2020 and October 2023. Six reviewers participated in the screening process in pairs, independently conducting study selection and data extraction. Conflicts were resolved by consensus. Citation tracking was performed, and data were summarized narratively in tables.<br><br>RESULTS: From 4256 initial hits and citation tracking, 8 reports were included. The studies were heterogeneous, including chart reviews, case reports, cross-sectional, and longitudinal studies. Evidence on the impact of Long COVID on pre-existing mental health conditions was inconsistent. Most findings focused on the course of mental health disorders, ranging from symptom worsening to new symptoms of anxiety, depression, or insomnia. Evidence on mental health care needs, service utilization, and psychosocial aspects was limited.<br><br>CONCLUSION: Limited evidence suggests that individuals with pre-existing mental health disorders who experience Long COVID may be at an increased risk of worsening mental health. However, critical aspects such as care needs, service utilization, and psychosocial factors remain under-researched, highlighting the need for further studies on mental health care for Long COVID.<br><br>REVIEW REGISTRATION: Open Science Framework https://osf.io/tqexa .<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid40595626,
year = {2025},
author = {Carreras-Vidal, L and Pacheco-Jaime, L and Ariza, M and Cano, N and Garolera, M and Garcia-Vicente, C and Roura, I and Capdevila-Lacasa, C and Oltra, J and Pardo, J and Martín-Barceló, C and Campabadal, A and Sala-Llonch, R and Bargallo, N and Barrué, C and Bejar, J and Cortés, CU and Junqué, C and , and Segura, B},
title = {Functional brain abnormalities in post COVID-19 condition and their relationship with cognition.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {22259},
pmid = {40595626},
issn = {2045-2322},
support = {LCF/BQ/DR22/11950012//'la Caixa' Foundation/ ; PRE2018-086675//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PRE2021-099674//Ministerio de Econom&#xed;a y Competitividad/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Brain/physiopathology/diagnostic imaging ; *Cognition/physiology ; *Cognitive Dysfunction/physiopathology/etiology/diagnostic imaging ; *COVID-19/complications/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {After COVID-19 infection, some patients develop a post-COVID condition (PCC) that is popularly referred to as long COVID. Among its symptoms is persistent cognitive dysfunction that is potentially linked to altered brain functional connectivity (FC). While research has explored functional reorganization in patients with PCC, the intra- and inter- network connectivity and its relationship with cognitive status and clinical outcomes remain unclear. In this study, we recruited 121 individuals with PCC (67 with, and 54 without, cognitive impairment), 20 months after infection, along with 37 non-infected healthy controls from the NAUTILUS Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575). Participants underwent resting-state functional magnetic resonance imaging and comprehensive neuropsychological assessment. Resting-state networks were characterized using independent component analyses, dual regression and network modelling for individual FC characterization. Group differences in intra- and inter-network FC, and their associations with clinical and neuropsychological data, were studied. Significance was set at a corrected p-value of < 0.05. Patients with PCC showed increased intra-network FC in 10 cognitively relevant networks, including the default mode, salience, executive control, auditory and basal ganglia networks, correlating positively with general cognition (Montreal Cognitive Assessment scores), time since infection, fatigue and subjective memory failures. Increased inter-network FC between default mode and sensorimotor networks was also observed. Increases in FC may reflect an inefficient compensatory mechanism in patients with PCC, associated with fatigue, subjective memory complaints and persistence of PCC.},
}
@article {pmid40593486,
year = {2025},
author = {Fraser, HL and Haag, L and Brosnahan, N and McConnachie, A and Richardson, J and Haig, CE and Ibbotson, T and Ormerod, J and O'Donnell, CA and Lean, MEJ and Sattar, N and Blane, DN and Combet, E and McIntosh, E},
title = {Cost-effectiveness of the ReDIRECT/counterweight-plus weight management programme to alleviate symptoms of long COVID.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5592},
pmid = {40593486},
issn = {2041-1723},
support = {COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; },
mesh = {Humans ; Cost-Benefit Analysis ; *COVID-19/economics/complications ; Female ; Male ; *Weight Reduction Programs/economics/methods ; Middle Aged ; United Kingdom ; Quality-Adjusted Life Years ; Adult ; *Obesity/therapy/economics/complications ; SARS-CoV-2 ; Quality of Life ; *Overweight/therapy/economics ; Aged ; },
abstract = {Long-term effects of COVID-19 infection, termed Long COVID (LC), are associated with reduced quality of life. Symptoms associated with overweight/obesity overlap with and may aggravate those of LC. This paper reports the economic evaluation alongside the ReDIRECT Trial, which evaluated the impact of an evidence-based, remotely-delivered weight management programme on self-reported symptoms of LC in those living with overweight/obesity in the United Kingdom. Recruited participants (n = 234) were randomly allocated to the intervention group (weight management) or control group (usual care). Incremental costs and Quality-Adjusted Life Years (QALYs) were calculated using intervention cost, healthcare resource use and EQ-5D-5L data collected at baseline, three and 6 months. In this work, we show that the ReDIRECT intervention is likely cost-effective in improving LC symptoms from an NHS/PSS perspective, compared to usual care (Incremental Cost-Effectiveness Ratio of £14,754/QALY). Adopting a broader societal perspective, the intervention becomes potentially cost saving compared to usual care.},
}
@article {pmid40591023,
year = {2025},
author = {Pennacchia, F and Zoccali, F and Petrella, C and Talarico, G and Rusi, E and Zingaropoli, MA and Ruqa, WA and Bruno, G and Capuano, R and Catini, A and Di Natale, C and Minni, A and Barbato, C},
title = {Insight into NeuroCOVID: neurofilament light chain (NfL) as a biomarker in post-COVID-19 patients with olfactory dysfunctions.},
journal = {Journal of neurology},
volume = {272},
number = {7},
pages = {484},
pmid = {40591023},
issn = {1432-1459},
support = {CUP B53D23018450006//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; },
mesh = {Humans ; *COVID-19/complications/blood ; Male ; Female ; *Neurofilament Proteins/blood ; *Olfaction Disorders/blood/etiology/diagnosis/virology ; Biomarkers/blood ; Middle Aged ; Pilot Projects ; Aged ; Adult ; Anosmia/blood/etiology ; },
abstract = {The term NeuroCOVID was coined to describe the neurological consequences observed in COVID-19 patients. Numerous patients infected with SARS-CoV-2 reported olfactory dysfunction as the first symptom preceding clinical manifestations, such as cough and fever, or even the only symptom, suggesting the sudden loss of smell or hyposmia as an important predictive factor for COVID-19 infection. Several patients developed long-term olfactory impairment, but to date there is not available a biochemical diagnosis of anosmia. The aim of this pilot study is to investigate the association between neurofilament light-chain (NfL) serum levels and the olfactory dysfunctions in post-COVID-19 patients. This study recruited patients who developed COVID-19 between January 2020 and August 2021. They were evaluated between October 2022 and March 2023 by Sniffin' Sticks tests to investigate deficits of odor identification, discrimination, and threshold and serum NfL biomarker measurement to assess a neuronal damage. Out of 27 patients, 11 were affected by post-viral permanent olfactory dysfunction (named Od-post-COVID-19) and 16 healed from the infection without residual Od problem, as a control group. We observed an increased levels of NfL 16.02 ± 1.91 pg/mL in Od-post-COVID-19, suggesting that NfL to be recognized as a biomarker of post-viral olfactory dysfunction, supporting the diagnostic process of NeuroCOVID, joined with other well-known neurological biomarkers and/or innovative investigative approaches.},
}
@article {pmid40590752,
year = {2025},
author = {Buonsenso, D},
title = {Not Having a Diagnostic Code for Long COVID Could Crash Healthcare Systems Like a Computer Bug.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {114},
number = {10},
pages = {2424-2426},
doi = {10.1111/apa.70192},
pmid = {40590752},
issn = {1651-2227},
}
@article {pmid40590624,
year = {2025},
author = {Ketata, N and Jdidi, J and Maamri, H and Baklouti, M and Issaoui, F and Olfa, C and Damak, J and Yaich, S and Mejdoub, Y and Hammami, R},
title = {Post-COVID Syndrome in Southern Tunisia: Prevalence, Clinical Spectrum, and Associated Factors Among Non-Severe Patients.},
journal = {Hospital topics},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/00185868.2025.2524796},
pmid = {40590624},
issn = {1939-9278},
abstract = {INTRODUCTION: Post-COVID syndrome, a long-term consequence of the COVID-19 pandemic, remains insufficiently understood. This study aimed to estimate the prevalence of post-COVID syndrome, describe its clinical spectrum, and identify associated factors among patients with non-severe forms of the disease.<br><br>METHODS: We conducted a cross-sectional study using telephone interviews in Sfax, southern Tunisia, during January 2021. The study population included individuals who tested positive for SARS-CoV-2 in October 2020. Minors and deceased individuals were excluded. Post-COVID syndrome was defined as the persistence of symptoms for more than eight weeks following the initial COVID-19 diagnosis.<br><br>RESULTS: A total of 2,070 patients were enrolled. The sample included 1,230 women (59.4%), with a male-to-female ratio of 0.68. The median age was 40&#x2009;years [semi-interquartile range (SIR): 12.5&#x2009;years]. The prevalence of post-COVID syndrome was 41.6% (n&#x2009;=&#x2009;861). Among these, 229 patients (26.5%) consulted a physician for persistent symptoms, and 122 (14.13%) underwent further paraclinical evaluation. The most commonly reported symptoms were ageusia (68.9%), cognitive difficulties including concentration and memory impairment (24.9%), and fatigue (17.4%). Independent factors significantly associated with post-COVID syndrome included: age under 60&#x2009;years (AOR = 1.8; 95% CI: 1.50-2.66), female gender (AOR = 1.6; 95% CI: 1.35-1.96), history of chronic respiratory disease (AOR = 1.8; 95% CI: 1.2-2.8), history of cancer (AOR = 3.5; 95% CI: 1.03-12.2), anticoagulant therapy (AOR = 1.45; 95% CI: 1.1-1.8), salicylic acid use (AOR = 1.4; 95% CI: 1.1-1.9), and initial clinical severity categorized as mild (AOR = 5.5; 95% CI: 3.5-8.5) or moderate (AOR = 7.1; 95% CI: 4.2-11.9).<br><br>CONCLUSION: A better understanding of the long-term manifestations of COVID-19, such as post-COVID syndrome, is essential. In the context of widespread vaccination and evolving variants, multidisciplinary approaches must be reconsidered to improve patient follow-up and healthcare strategies.},
}
@article {pmid40590080,
year = {2025},
author = {Goh, DY and Lam, WC and Zhong, LLD},
title = {Effect of interventions for the management of sleep disturbances in patients with long COVID: a systematic review and meta-analysis of randomized controlled trials.},
journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine},
volume = {21},
number = {11},
pages = {1993-2005},
pmid = {40590080},
issn = {1550-9397},
mesh = {Humans ; *COVID-19/complications ; *Sleep Wake Disorders/therapy/etiology ; Randomized Controlled Trials as Topic ; Quality of Life ; SARS-CoV-2 ; },
abstract = {STUDY OBJECTIVES: Long COVID presents with symptoms that persist for weeks or months postinfection, with sleep disturbances that significantly affect quality of life. The diverse approaches to managing sleep disturbances highlight the need for comparing treatment effectiveness to improve patient outcomes. This study systematically reviews and conducts a meta-analysis of randomized controlled trials to assess the effectiveness of current interventions for sleep disturbances in patients with long COVID and explores the underlying mechanisms and promising treatments.<br><br>METHODS: Relevant studies were identified through a comprehensive literature search across Embase, Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data databases. The included studies focused on interventions aimed at managing patients with long COVID with sleep disturbances. Data extraction and analysis were performed, followed by a meta-analysis of comparable studies. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (RoB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation system.<br><br>RESULTS: Out of 3,352 retrieved studies, 14 were included in the systematic review and 2 in the meta-analysis. Interventions were categorized as pharmacological and nonpharmacological. Whereas most studies indicated improved sleep quality measured by standardized scales, some did not demonstrate significant benefits. The quality of evidence varied from low to moderate.<br><br>CONCLUSIONS: The results suggest that sleep disturbances in patients with long COVID result from a complex interplay of physiological, psychological, and neurological factors. Both pharmacological and nonpharmacological interventions show potential in managing these disturbances, with nonpharmacological approaches showing particular promise. To establish more robust evidence, more high-quality, large-scale randomized controlled trials are necessary in future research.<br><br>CITATION: Goh DY, Lam WC, Zhong LLD. Effect of interventions for the management of sleep disturbances in patients with long COVID: a systematic review and meta-analysis of randomized controlled trials. J Clin Sleep Med. 2025;21(11):1993-2005.},
}
@article {pmid40589858,
year = {2025},
author = {Saikarthik, J and Saraswathi, I and Padhi, BK and Shamim, MA and Alzerwi, N and Alarifi, A and Gandhi, AP},
title = {Structural and functional neuroimaging of hippocampus to study adult neurogenesis in long COVID-19 patients with neuropsychiatric symptoms: a scoping review.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19575},
pmid = {40589858},
issn = {2167-8359},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; *Hippocampus/diagnostic imaging/physiopathology/pathology ; *Neurogenesis/physiology ; SARS-CoV-2 ; Adult ; *Functional Neuroimaging ; *Mental Disorders/diagnostic imaging/physiopathology ; Neuroimaging ; Magnetic Resonance Imaging ; },
abstract = {BACKGROUND: Worsening of neuropsychiatric and neurodegenerative disorders occurs in COVID-19. Impaired adult neurogenesis is linked to most of the neuropsychiatric symptoms and disorders.<br><br>AIM: The current scoping review identified and mapped the available evidence on adult neurogenesis in long COVID-19, at a global level following the JBI methodology for scoping reviews and followed the framework by Arksey and O'Malley.<br><br>METHOD: Original studies focusing on structural and functional neuroimaging of the hippocampus to study adult neurogenesis in long COVID-19 were included in the review. Studies published in English language with no restriction on the time of publication were searched using the specified search strategy in PubMed, Web of Science, Embase, and SCOPUS. Articles obtained from the database search were collated and uploaded into the Nested Knowledge AutoLit semi-automated systematic review platform for data extraction.<br><br>RESULTS: The current review provides evidence of the potential alterations in adult neurogenesis in long COVID-19 and its potential link to neuropsychiatric sequelae of long COVID-19, with further research required to validate this assertion.<br><br>CONCLUSION: This review proposes conceptual and methodological approaches for future investigations to address existing limitations and elucidate the precise role of adult neurogenesis in the pathophysiology and treatment of long COVID-19.},
}
@article {pmid40589563,
year = {2025},
author = {Ohira, M and Osada, T and Kimura, H and Sano, T and Takao, M},
title = {Contemporary positive signs of functional limb weakness in post-acute sequelae of SARS-CoV-2: an exploratory analysis of their utility in diagnosis and follow-up.},
journal = {BMJ neurology open},
volume = {7},
number = {1},
pages = {e000995},
pmid = {40589563},
issn = {2632-6140},
abstract = {BACKGROUND: Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND. This study confirmed positive signs of functional limb weakness (hereafter positive signs) in patients with long COVID.<br><br>METHODS: This was an observational, retrospective, single-centre study at an outpatient clinic conducted from 1 June 2021 to 31 May 2024. We collected patients' clinical data, including positive signs. The primary outcome was the prevalence of positive signs. Patients with positive signs were followed up over 2 months, and subjective patient perceptions of symptomatic improvements and changes in positive signs were analysed.<br><br>RESULTS: Overall, 502 were diagnosed with long COVID, and 100 assessed patients had positive signs. Female sex, time of infection after 2022, comorbidity of psychiatric diseases, fatigue, headache and muscle weakness were statistically significant in patients with positive signs compared with those in patients without positive signs. 89 patients (41 with positive signs and 48 without positive signs) were followed up, and 28 (68.3%) with positive signs and 33 (68.8%) without positive signs reported improvements. Positive signs disappeared in patients with symptomatic improvements but not in patients without symptomatic improvements (p=0.0001).<br><br>CONCLUSIONS: Positive signs were found in over one-third of patients (33.9%) who were investigated in this study. Some positive signs disappeared concurrently with their symptomatic improvement.},
}
@article {pmid40589358,
year = {2025},
author = {Choi, S and Hong, Y and Kang, MK and Song, TJ and Cho, SJ},
title = {Calcitonin Gene-Related Peptide Monoclonal Antibody Treatment in Nine Cases of Persistent Headache Following COVID-19-Infection.},
journal = {Journal of Korean medical science},
volume = {40},
number = {25},
pages = {e127},
pmid = {40589358},
issn = {1598-6357},
support = {RS-2022-II220621//Institute of Information &amp; Communications Technology Planning &amp; Evaluation/Korea ; /KEIT/Korea Evaluation Institute of Industrial Technology/Korea ; RS-2023-00262087/MOHW/Ministry of Health and Welfare/Korea ; },
mesh = {Humans ; Female ; Middle Aged ; *COVID-19/complications ; *Calcitonin Gene-Related Peptide/immunology/antagonists &amp; inhibitors ; Retrospective Studies ; Adult ; *Headache/drug therapy/etiology ; *Antibodies, Monoclonal/therapeutic use ; Quality of Life ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Male ; Aged ; },
abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has underscored the need for effective treatment for post-infectious complications, including headaches. Owing to the variable nature of post-COVID headaches, identifying effective therapies through clinical trials is challenging and the burden on patients is often severe. This study aimed to summarize the presentation of post-COVID headache in clinical practice and evaluate its response to treatment with calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs).<br><br>METHODS: In this retrospective cohort study, medical records obtained between March 2022 and May 2024 from two centers were analyzed. The study included nine patients with new-onset or significantly worsening or altered patterns of previous headaches lasting more than one month after COVID-19 infection who subsequently received CGRP mAbs. Demographics, headache frequency and severity, medication use, and quality of life were assessed before and after CGRP mAb treatment.<br><br>RESULTS: All patients were female (median age, 48 years), and 88.9% had headaches for more than three months despite conventional preventive therapies. Headache Impact Test-6 (HIT-6) scores were greater than 60 in all patients, and the headaches were unilateral (66.7%) and pulsating (22.2%). After CGRP mAb treatment, the monthly headache days, headache severity scores, and monthly medication days decreased significantly (median with interquartile range: 25 [15-28] to 5 [4-10], P = 0.012; 8 [7-9] to 3 [2-4], P = 0.011; 16 [15-20] to 5 [4-10], P = 0.017). The HIT-6 (65 [60-68] to 48 [48-60], P = 0.017) and Patient Health Questionnaire-9 scores (14 [5-15] to 10 [4-12], P = 0.028) also decreased significantly after treatment.<br><br>CONCLUSION: CGRP mAbs may be considered a potential treatment option for persistent headaches following COVID-19, especially the long-COVID headaches. Their use may contribute to an improved burden of headache and quality of life and may help alleviate the psychological symptoms associated with persistent headaches.},
}
@article {pmid40587610,
year = {2024},
author = {Butler, CS},
title = {Use of Neuromodulation to Treat Post-COVID Neuropathic Pain: A Case Report.},
journal = {Pain medicine case reports},
volume = {8},
number = {7},
pages = {253-256},
pmid = {40587610},
issn = {2768-5152},
mesh = {Humans ; Male ; *Neuralgia/therapy/etiology ; Adult ; *COVID-19/complications ; *Electric Stimulation Therapy/methods ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-COVID-19 neuropathic pain is a difficult-to-treat condition seen in approximately one-third of patients with long COVID. It has been shown to be resistant to many first-line therapies as well as over-the-counter and prescription medications.<br><br>CASE REPORT: We present the case of a 27-year-old man who developed bilateral upper extremity neuropathic pain in conjunction with a severe COVID-19 infection. He failed occupational therapy, multiple medications, and a stellate ganglion block. A dorsal column stimulator was placed and provided the patient with both pain relief and improved functionality.<br><br>CONCLUSIONS: Given the results of this case and the history of neuromodulation in effectively treating neuropathic pain, we submit that neuromodulation is a viable option for patients with refractory post-COVID-19 neuropathic pain.},
}
@article {pmid40587609,
year = {2024},
author = {Escano Volquez, LM and Kanuri, SH and Haddad, R},
title = {Tibial Nerve Mononeuropathy Post-COVID-19 and Successful Management with Peripheral Nerve Stimulation: A Case Report.},
journal = {Pain medicine case reports},
volume = {8},
number = {7},
pages = {249-252},
pmid = {40587609},
issn = {2768-5152},
mesh = {Humans ; Female ; *COVID-19/complications ; Adult ; *Tibial Nerve ; *Mononeuropathies/therapy/etiology ; *Neuralgia/therapy/etiology ; *Transcutaneous Electric Nerve Stimulation/methods ; *Tibial Neuropathy/therapy/etiology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Infection with COVID-19 has evolved from a novel health crisis into an entity with a myriad of increasingly recognized sequelae. Among these, peripheral neuropathy is often an underrecognized and underdiagnosed complication. Neuropathic pain can be challenging to treat with many cases being refractory to conservative management, often requiring advanced techniques. Neuromodulation has become an important tool for the treatment of the refractory cases.<br><br>CASE REPORT: We present a case of a 43-year-old woman with refractory right tibial mononeuropathy secondary to COVID-19 infection who was treated successfully using peripheral nerve stimulation.<br><br>CONCLUSIONS: The use of peripheral neuromodulation represents a pivotal strategy for the management of difficult cases. Our case highlights the first use of neuromodulation to treat neuropathic pain secondary to COVID-19 infection. We hope that this case sparks further research on the topic, which could lead to better clarification of this condition and potential expansion of treatment strategies.},
}
@article {pmid40586228,
year = {2025},
author = {Madrigal, M and Velasco-Gonzalez, V and Jiménez-Navascués, L and Cárdaba-García, RM and Durantez-Fernández, C and Bahillo Ruiz, E and Pérez-Pérez, L and Olea, E and Muñoz-Del Caz, A},
title = {Relationship Between Fatigue, Perceived Social Support and Symptomatology of Long-COVID Patients in Spain.},
journal = {Scandinavian journal of caring sciences},
volume = {39},
number = {3},
pages = {e70078},
pmid = {40586228},
issn = {1471-6712},
mesh = {Humans ; Spain/epidemiology ; Female ; *Fatigue/epidemiology/etiology ; Male ; *Social Support ; Middle Aged ; *COVID-19/complications/psychology/epidemiology/physiopathology ; Cross-Sectional Studies ; Adult ; Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {AIMS AND OBJECTIVES: Long-COVID, identified in approximately 15% of symptomatic cases of COVID-19 in Spain, is a chronic multiorgan disease characterised by persistent symptoms, such as fatigue, dyspnoea, and cognitive difficulties. This study aims to evaluate the relationship between fatigue, perceived social support, and symptomatology in Spanish patients with Long-COVID, with the objective of identifying variables that contribute to holistic care.<br><br>An observational, descriptive, cross-sectional study was conducted with a non-randomised sample of 374 patients belonging to Spanish associations of Long-COVID patients. It was conducted using self-administered questionnaires distributed between July and November 2022 through associations of patients with Long-COVID.<br><br>ETHICAL ISSUES AND APPROVAL: Ethical evaluation was requested by the research ethics committee of the Eastern Area of Valladolid, which granted approval with registration number PI-22-2747.<br><br>RESEARCH METHODS: A total of 374 individuals who met specific criteria, including proficiency in Spanish and persistent symptoms, participated. Sociodemographic variables, persistent symptomatology, levels of fatigue (FSS scale), and perceived social support (DUKE-UNC-11 scale) were assessed. Descriptive statistical analysis, linear regression, and logistic analysis were employed to determine associations between variables.<br><br>RESULTS: The sample predominantly consisted of women (79.9%) with a mean age of 47&#x2009;years. Neurological symptoms (79.4%) and pain (75.9%) were the most prevalent. Notably, 54.5% of participants experienced severe fatigue, which was negatively correlated with perceived social support. Conversely, perceived social support exhibited a significant association with neurological, psychic, and pain symptoms. Additionally, variables such as age and fatigue level predicted affective and confidential social support.<br><br>CONCLUSION: Fatigue and pain are associated with low perceptions of social support, underscoring the necessity of integrating psychosocial assessments into care protocols for patients with Long-COVID. An approach focused on perceived social support could enhance the adaptation of these patients, contributing to a more comprehensive and personalised model of care.},
}
@article {pmid40585077,
year = {2025},
author = {Wells, AM and Rolin, S and Robles-Ramamurthy, B and Gibson-Lopez, G and Goros, M and Gelfond, JA and Gelfond, S and Balfanz, P and Deuter, M and McGeary, D and Verduzco-Gutierrez, M},
title = {Assessing Neuropsychiatric Symptoms in Long COVID: A Retrospective Cohort Study from a South Texas Long COVID Clinic.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40585077},
support = {F30 MH134482/MH/NIMH NIH HHS/United States ; T32 GM113896/GM/NIGMS NIH HHS/United States ; T32 NS082145/NS/NINDS NIH HHS/United States ; T32 GM145432/GM/NIGMS NIH HHS/United States ; R25 NS089462/NS/NINDS NIH HHS/United States ; UM1 TR004538/TR/NCATS NIH HHS/United States ; },
abstract = {Long COVID, previously known as Post-Acute Sequelae of SARS-CoV-2 (PASC), refers to prolonged symptoms or diagnosable conditions following COVID-19 infection. The neuropsychiatric profile of Long COVID patients remains ambiguous. This study aimed to assess neuropsychiatric symptoms in a retrospective cohort of Long COVID patients (N = 162) at a Rehabilitation Medicine clinic in South Texas. Clinical data from patient records were used to calculate a Symptom Score, and screening tools for stress/PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and quality of life (SWL) were employed to evaluate if Long COVID duration and severity could predict neuropsychiatric outcomes. The majority were female (71%) and Hispanics (53%) who presented for treatment of Long COVID symptoms during the study period, including fatigue (93%), coughing/shortness of breath (81%), fever (67%), anosmia (58%), ageusia (54%), and weight loss (56%). A minority of participants were hospitalized (N = 49) or required ventilator support (N = 5) during acute infection. There was a high burden of neuropsychiatric symptoms, including subjective cognitive impairment (79%), headache (74%), and insomnia (58%). Symptom Score (median = 9, IQR [8,11]) was significantly correlated with increased depression (PHQ-9; p < 0.05), anxiety (GAD-7; p < 0.05) and elevated stress/PTSD (PCL-5; p < 0.05) symptoms. Long COVID patients taking stimulants or mood stabilizers had higher GAD-7 (p < 0.031, p < 0.035) and PHQ-9 (p < 0.034, p < 0.009) scores but not PCL-5 scores. Importantly, duration of Long COVID symptomatology also did not predict PCL-5 scores. No patient factors (e.g., sex, age, BMI, ethnicity) mediated Symptom Score. Nonetheless, historically marginalized groups, such as women and Hispanics, have been disproportionately affected by COVID-19. This study is the first to utilize validated screening tools to determine the presence and severity of neuropsychiatric symptoms in Long COVID patients. These findings may guide clinical management and future research on Long COVID, especially in historically excluded populations.},
}
@article {pmid40584711,
year = {2025},
author = {Garbsch, R and Kotewitsch, M and Schäfer, H and Teschler, M and Mooren, FC and Schmitz, B},
title = {Use of speleotherapy in patients with post-COVID-19 syndrome.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1566235},
pmid = {40584711},
issn = {2296-858X},
abstract = {BACKGROUND: The post-COVID-19 syndrome (PCS) is characterized by persistent or newly developed symptoms and performance deficits lasting at least 3 months following SARS-CoV-2 infection, with dyspnea as a common symptom. Speleotherapy, a form of climatotherapy utilizing the microclimatic conditions of natural or artificial caves, has been proposed as a supportive treatment for chronic airway diseases, potentially improving lung function and exercise tolerance.<br><br>METHODS: This study investigated the short-term effects of speleotherapy on lung diffusion capacity (DLCO) in PCS patients through a prospective interrupted time-series analysis. Forty-six patients (51.9&#x202f;&#xb1;&#x202f;9.3&#x202f;years; 43% female) referred for rehabilitation were included, with a history of COVID-19 infection and persistent deficits lasting over 3&#x202f;months. Patients underwent spirometric assessments of DLCO repeatedly on days without speleotherapy intervention and on days with intervention, alongside subjective symptom evaluations using the Nijmegen questionnaire.<br><br>RESULTS: PCS patients performed a median of four out of seven speleotherapy sessions during rehabilitation, resulting in a total of 388 measurements. Analysis revealed no significant changes in DLCO or related parameters (transfer coefficient (KCO), inspiratory volume (IV), total lung capacity (TLC), Residual volume (RV)) during rehabilitation and between speleotherapy and control days (p&#x202f;&#x2265;&#x202f;0.544). Subgroup analysis of patients with DLCO below 80% of predicted reference and symptom severity assessments also revealed no therapeutic benefits. Speleotherapy frequency showed no dose-dependent effects on pulmonary outcomes (p&#x202f;=&#x202f;0.171). Findings from a small control group confirmed these results (p&#x202f;&#x2265;&#x202f;0.997).<br><br>CONCLUSION: Speleotherapy did not improve DLCO or alleviate symptoms in PCS patients within this study cohort. Further research is needed to investigate whether speleotherapy can alleviate pulmonary dysfunction in different PCS populations.},
}
@article {pmid40583757,
year = {2025},
author = {Cornwell, WK and Levine, BD and Baptiste, D and Bhave, N and Desai, S and Dineen, E and Durstenfeld, M and Edward, J and Huang, M and Jacobsen, R and Kim, JH and Spatz, E and , },
title = {Exercise Intolerance and Response to Training in Patients With Postacute Sequelae of SARS-CoV2 (Long COVID): A Scientific Statement From the American Heart Association.},
journal = {Circulation},
volume = {152},
number = {5},
pages = {e50-e62},
doi = {10.1161/CIR.0000000000001348},
pmid = {40583757},
issn = {1524-4539},
mesh = {Humans ; *COVID-19/physiopathology/complications/therapy ; *Exercise Tolerance ; American Heart Association ; United States ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Exercise Therapy/methods ; Cardiovascular Deconditioning ; Quality of Life ; Exercise ; },
abstract = {The postacute sequelae of SARS-CoV-2, also known as Long COVID, may affect 10% to 25% of individuals diagnosed with SARS-CoV-2. More than 100 symptoms have been reported among patients with Long COVID, but almost all patients report severe fatigue, orthostatic intolerance, shortness of breath, and reductions in exercise tolerance. Emerging data suggest that cardiovascular deconditioning plays a major role in the development of this syndrome and that reductions in functional capacity among patients with Long COVID are comparable to reductions seen among individuals with cardiovascular deconditioning resulting from bed rest. Concern has been raised about the use of exercise training as part of the management strategy for patients with Long COVID. However, exercise training appropriately tailored to the patient with cardiovascular deconditioning may be an effective strategy to facilitate improvement in symptoms. This American Heart Association scientific statement provides a concise yet comprehensive overview of mechanisms contributing to development of Long COVID and methods by which exercise training may be applied to this unique patient population to alleviate symptoms and improve quality of life. In addition, methods of reintroducing exercise and return to play among athletes affected by COVID-19 are discussed.},
}
@article {pmid40583236,
year = {2025},
author = {Tracy, MF and Hagstrom, S and Mathiason, MA and Wente, S and Lindquist, R},
title = {Longitudinal Multidimensional Symptom Experience Following COVID-19 Hospitalization: Implications from a Holistic Perspective.},
journal = {Western journal of nursing research},
volume = {47},
number = {9},
pages = {844-853},
doi = {10.1177/01939459251349753},
pmid = {40583236},
issn = {1552-8456},
support = {UL1 TR002494/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/complications/psychology/therapy ; Longitudinal Studies ; Female ; Male ; Middle Aged ; *Hospitalization/statistics &amp; numerical data ; *Quality of Life/psychology ; Adult ; Aged ; Fatigue/etiology ; *Holistic Health ; SARS-CoV-2 ; United States ; },
abstract = {BACKGROUND: While COVID-19 has lessened in urgency for the general United States population's day-to-day functioning, it continues to have significant impact for those who live with a wide range of ongoing sequelae. Wide variation of Long COVID symptoms must be considered as nurses facilitate holistic patient-centered care.<br><br>OBJECTIVES: We aimed to describe patients' symptom experiences from 3 to 12&#x2009;months following COVID-19 hospitalization.<br><br>METHODS: A longitudinal descriptive design was used to explore adults' symptom experiences of Long COVID at 4 time points up to 12&#x2009;months following hospital admission for COVID-19 between October 2020 and May 2022.<br><br>RESULTS: Most of the 37 participants (87%) continued to experience at least 1 physical symptom at 12&#x2009;months, which was not significantly different than at 3&#x2009;months (90%). Fatigue was the most common symptom reported at all the time points. Group mean scores on all PROMIS measures and the Impact of Events Scale-Revised did not indicate dysfunction; however, 37% reported having somewhat or a lot of symptom impact on their normal routines. In addition, at least 50% reported currently experiencing quality of life worse than prior to COVID at each time point.<br><br>CONCLUSIONS: Long COVID symptoms continue to affect significant numbers of people with ongoing impact to daily routines and quality of life. Nurses are in a unique position to generate new evidence on identifying the subset of patients recovering from COVID-19 who are at higher risk for developing Long COVID and provide holistic assessments, monitoring, and interventions to mitigate patients' physical, emotional, and mental health symptoms.},
}
@article {pmid40582622,
year = {2025},
author = {Xu, K and He, W and Yu, B and Wang, JJ and Wu, J and Wang, DW},
title = {Unveiling the silent threat: COVID-19 and myocardial injury.},
journal = {Pharmacology &amp; therapeutics},
volume = {273},
number = {},
pages = {108904},
doi = {10.1016/j.pharmthera.2025.108904},
pmid = {40582622},
issn = {1879-016X},
mesh = {Humans ; *COVID-19/complications ; *Myocarditis/etiology/virology/diagnosis ; COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; COVID-19 Drug Treatment ; },
abstract = {Since COVID-19 firstly appeared in 2019 December, it has been defined as an infectious disease mainly performing lung symptoms, which contracted more attention. However, more and more findings indicate myocardial injury appears in considerable proportion of COVID-19 patients (30 % - 50 %) not only but also major cause leading to the death in patients, many of whom may be even without severe respiratory symptoms. Meanwhile myocarditis after injecting vaccines has been paid more attention to globally which always performs uncontrollable inflammation and lead to death. Now myocardial injury has been a main complication in patients with long COVID-19, which is worthy of attention. Furthermore, myocardial injury or myocarditis is detectable and treatable. In order to abstract attention to myocardial injury associated with COVID-19 and provide more evidence and experience for patients who still suffer myocardial injury from COVID-19 vaccines or long COVID-19, the review comprehensively summarized previous researches from pathogenesis, clinical symptoms, diagnosis and treatment and emphasized the crucial role of RASS inhibitors especially ARBs.},
}
@article {pmid40580194,
year = {2026},
author = {Gorenshtein, A},
title = {Neuroprotection of medical gases: a potential effect on treating cognitive impairments in neurological symptoms of long-COVID.},
journal = {Medical gas research},
volume = {16},
number = {1},
pages = {84-85},
pmid = {40580194},
issn = {2045-9912},
}
@article {pmid40579261,
year = {2025},
author = {Chen, YC and Chiu, CH and Chen, CJ},
title = {Neurological and psychiatric aspects of long COVID among vaccinated healthcare workers: An assessment of prevalence and reporting biases.},
journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi},
volume = {58},
number = {6},
pages = {670-677},
doi = {10.1016/j.jmii.2025.06.002},
pmid = {40579261},
issn = {1995-9133},
mesh = {Humans ; *Health Personnel/psychology/statistics &amp; numerical data ; *COVID-19/epidemiology/psychology/prevention &amp; control/complications ; Male ; Female ; Adult ; Taiwan/epidemiology ; Prevalence ; Middle Aged ; *COVID-19 Vaccines/administration &amp; dosage ; SARS-CoV-2 ; Surveys and Questionnaires ; Depression/epidemiology ; Anxiety/epidemiology ; Vaccination ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; },
abstract = {BACKGROUND: This study assessed the prevalence and severity of neurological and psychiatric long COVID symptoms among healthcare workers (HCWs) based on their COVID-19 status, aiming to unravel the complexities associated with post-acute sequelae of SARS-CoV-2 infection.<br><br>METHODS: A cohort of 467 HCWs from a teaching hospital in northern Taiwan, who received at least three doses of COVID-19 vaccines, were surveyed for long COVID symptoms. Participants were categorized into symptomatic (n&#xa0;=&#xa0;224), asymptomatic (n&#xa0;=&#xa0;21), and absence of COVID-19 (n&#xa0;=&#xa0;222) groups based on diagnostic criteria involving questionnaire responses, medical records, and anti-nucleoprotein antibody data. Through a comprehensive set of questionnaires, symptoms, memory dysfunction, anxiety, and depression were rigorously evaluated and statistically analyzed for group comparisons.<br><br>RESULTS: Despite meticulous data collection, the study revealed no statistically significant differences in the severity of neurological and psychiatric long COVID symptoms across the COVID-19 status groups. Noteworthy trends were observed, including higher instances of memory problems worsening over time, elevated anxiety levels in symptomatic cases, and subtle indicators of increased depression severity in this subgroup. The findings underscored the multifactorial nature of long COVID manifestations and the impact of COVID-19 history on reported symptoms.<br><br>CONCLUSION: The study highlighted potential biases in symptom reporting that may inflate long COVID prevalence estimates. While the robust methodology shed light on diverse health profiles among HCWs, future research should focus on longitudinal designs and objective diagnostic measures to provide more accurate assessments of long COVID's burden.},
}
@article {pmid40578337,
year = {2025},
author = {Menson, KE and Gaalema, DE},
title = {When the Treatment Needs a Home: The Application of Exercise Interventions in Long COVID.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {45},
number = {4},
pages = {233-235},
pmid = {40578337},
issn = {1932-751X},
}
@article {pmid40578132,
year = {2025},
author = {Shady, EFA and Ghallab, AF and Shaker, DA and Elsayed, RAE},
title = {Epstein-Barr virus (EBV) reactivation in post COVID-19.},
journal = {Auris, nasus, larynx},
volume = {52},
number = {4},
pages = {442-446},
doi = {10.1016/j.anl.2025.06.009},
pmid = {40578132},
issn = {1879-1476},
mesh = {Humans ; *COVID-19/complications/virology ; Male ; Female ; *Virus Activation ; *Herpesvirus 4, Human/physiology ; Middle Aged ; Case-Control Studies ; *Epstein-Barr Virus Infections/virology/complications ; Adult ; SARS-CoV-2 ; Fatigue/virology ; Antibodies, Viral/blood ; Aged ; Egypt ; Epstein-Barr Virus Nuclear Antigens/immunology ; },
abstract = {OBJECTIVE: To determine if there is a link between prolonged COVID symptoms and the reactivation of EBV.<br><br>METHODS: This study was an observational (case-control) analysis involving 140 patients who tested positive for COVID-19 and are experiencing persistent symptoms such as fatigue and post-exertional malaise. Additionally, a control group of 80 individuals, matched for age and gender, who have fully recovered from SARS-CoV-2 infection without these symptoms, was included. The research took place between December 2023 and March 2024 at Benha University Hospitals in Benha, Egypt. The reactivation of the Epstein-Barr virus (EBV) was identified by detecting EBV genetic material using TaqMan probes, along with at least one set of primers (BamHI and LMP2).<br><br>RESULTS: Initial hospitalization during acute COVID-19 infection is significantly associated with post-COVID fatigue (p-value 0.007*). No significant associations were found for risk factors like diabetes and hypertension. EBV replication observed was due to EBV reactivation rather than primary infection. EBV-specific antibody titers EBNA-1 IgG (p-value 0.004*) and EA-D IgG (p-value 0.008*). 40/140 (28.6 %) patients with COVID-19 with persistent fatigue showed EBV reactivation in contrast to 9/80 (11.3 %) of controls (P-value 0.003*) using the same detection methods.<br><br>CONCLUSION: EBV reactivation plays a role in Long-COVID syndrome following COVID-19 infection supporting the usage of EBV inhibitors for long-term COVID-19 treatment.},
}
@article {pmid40576557,
year = {2025},
author = {Openshaw, JJ and Chen, J and Rodriguez, R and Gottlieb, M and McCullough, K and Santangelo, M and Hill, MJ and Gatling, K and Idris, AH and McDonald, S and Wisk, LE and Dyal, J and Wang, RC and Rising, KL and Kean, E and O'Laughlin, KN and Stephens, KA and Malicki, C and Lin, Z and Spatz, ES and Yu, H and Weinstein, RA and Elmore, J},
title = {The Effect of SARS-CoV-2 Reinfection on Long-Term Symptoms in the Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE).},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {81},
number = {3},
pages = {416-426},
pmid = {40576557},
issn = {1537-6591},
support = {/CC/CDC HHS/United States ; 75D30120C08008/IP/NCIRD CDC HHS/United States ; /CC/CDC HHS/United States ; 75D30120C08008/IP/NCIRD CDC HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Reinfection/epidemiology/virology ; Male ; Female ; Registries ; Middle Aged ; *SARS-CoV-2 ; Aged ; Adult ; Fatigue ; },
abstract = {BACKGROUND: The clinical consequences of repeated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not clear, especially as they relate to long-term symptoms after infection. We analyzed data collected for the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) to determine whether reinfection changes the likelihood of symptoms 3-6 months after reinfection compared with the likelihood in individuals experiencing a single infection.<br><br>METHODS: Individuals reporting a single SARS-CoV-2 infection or a single reinfection were included in this analysis. A positive SARS-CoV-2 test occurring &#x2265;90 days after a first infection was considered a reinfection. Outcomes included severe fatigue (fatigue severity score &#x2265;25) and the presence of organ system symptoms 3-6 months after the last infection.<br><br>RESULTS: The analysis included 886 individuals, 415 (46.8%) of whom experienced reinfection. For individuals who experienced their first infections in either the pre-Delta or Delta periods, the odds of having &#x2265;3 symptoms 3-6 months after their most recent infection was lower in those reinfected than those with a single infection (weighted adjusted odds ratio, 0.45 [95% confidence interval, .21-.95] and 0.51 [.32-.79], respectively). However, in individuals reporting their first infection during the Omicron wave, the odds of reporting &#x2265;3 symptoms after the most recent infection was higher in those reinfected than in those with a single infection (weighted adjusted odds ratio, 1.54 [95% confidence interval, 1.02-2.34]).<br><br>CONCLUSIONS: The timing of initial infection, reinfection, and the variants involved may play important roles in longer-term clinical outcomes. Repeated infection with Omicron variants may increase the risk of long-term symptoms.},
}
@article {pmid40575972,
year = {2025},
author = {Zhu, T and Li, X and Gao, S and Cui, R and Wang, J and Deng, Q},
title = {Successful salvage therapy of ruxolitinib on interstitial pneumonia after long COVID or post-COVID-19 syndrome with follicular lymphoma: two case reports and literature review.},
journal = {Chinese clinical oncology},
volume = {14},
number = {3},
pages = {35},
doi = {10.21037/cco-24-106},
pmid = {40575972},
issn = {2304-3873},
mesh = {Humans ; Nitriles ; *Pyrazoles/therapeutic use ; *COVID-19/complications ; Pyrimidines ; *Lymphoma, Follicular/complications/drug therapy ; *Salvage Therapy/methods ; Male ; SARS-CoV-2 ; Middle Aged ; Female ; *Lung Diseases, Interstitial/drug therapy/etiology ; COVID-19 Drug Treatment ; Aged ; Methylprednisolone/therapeutic use ; },
abstract = {BACKGROUND: Immunocompromised patients with B lymphocyte deficiency and hypogammaglobulinemia after anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory follicular lymphoma (FL) are at high risk of severe coronavirus disease 2019 (COVID-19) infection.<br><br>CASE DESCRIPTION: In our study, two patients with refractory FL had persistent COVID-19 infection after their anti-CD19 CAR T cell therapy. The patients were diagnosed with post-COVID-19 syndrome or COVID-19 with interstitial inflammation and persistent hypoxemia. The patients received molnupiravir and Paxlovid, along with methylprednisolone therapy when their interleukin (IL)-6 levels were high. No response was observed in interstitial inflammation, persistent hypoxemia, or persistent positive expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the level of IL-6 decreased after these therapies. These two patients subsequently received low-dose ruxolitinib (5 mg, twice daily) as salvage therapy in combination with a gradually reduced dosage of methylprednisolone. After 1-2 months of ruxolitinib therapy, persistent hypoxemia was relieved, and interstitial inflammation was significantly absorbed. At the same time, the SARS-CoV-2 detection was found to be negative.<br><br>CONCLUSIONS: Ruxolitinib might be a safe and effective alternative salvage therapy for patients with COVID-19 having interstitial inflammation and persistent hypoxemia without high cytokine levels and no response to corticosteroids.},
}
@article {pmid40574623,
year = {2025},
author = {Yang, J and Tamberou, C and Arnee, E and Squara, PA and Boukhlal, A and Nguyen, JL and Volkman, HR and Fievez, S and Lepoutre-Bourguet, M and Ben Romdhane, H and Renaudat, C and Crépey, P and Robineau, O},
title = {Quantifying all-cause healthcare resource utilization and costs of children with mild-to-moderate long COVID in France.},
journal = {Journal of medical economics},
volume = {28},
number = {1},
pages = {1002-1013},
doi = {10.1080/13696998.2025.2525002},
pmid = {40574623},
issn = {1941-837X},
mesh = {Humans ; Child ; France/epidemiology ; *COVID-19/economics/epidemiology/therapy ; Female ; Retrospective Studies ; Male ; Child, Preschool ; Adolescent ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; SARS-CoV-2 ; Infant ; Primary Health Care/economics ; Comorbidity ; *Health Expenditures/statistics &amp; numerical data ; Severity of Illness Index ; },
abstract = {BACKGROUND: Although children are known to be at risk of developing long COVID, its economic burden is poorly described. We aimed to assess the all-cause healthcare resource utilization (HCRU) and associated direct medical costs of children with mild-to-moderate long COVID in France.<br><br>METHODS: This retrospective cohort study utilized The Health Improvement Network (THIN) primary care electronic health records to identify children aged <18&#x2009;years with confirmed/probable COVID-19 diagnoses during March 2020 to December 2022 who developed long COVID, identified per the World Health Organization as suggestive symptoms present &#x2265;3&#x2009;months following SARS-CoV-2 infection. Patient characteristics, all-cause HCRU and direct healthcare costs from a national health insurance perspective were summarized. HCRU and costs were stratified into healthcare encounters, medical procedures, retail pharmacy usage, testing, caregiver sick leave, medical transport, and medical device usage.<br><br>RESULTS: Of 27,537 children diagnosed with acute COVID-19, 3,888 (14.1%) developed long COVID; mean age was 8.9&#x2009;years, 49.2% were female and, among those with comorbidity, 24.5% had a Charlson Comorbidity Index score &#x2265;1. During a mean post-diagnosis follow-up of 12.6&#x2009;months, 93.6% of children had general practitioner consultations, 93.5% had pharmacy usage, and 61.0% had medical procedures. First-year costs were highest at &#x20ac;823 per patient per year; 4.3% of children required caregiver-related work absenteeism. Compared to children who did not develop long COVID, a long COVID diagnosis was associated with an incremental cost increase of &#x20ac;98 per patient per year.<br><br>LIMITATIONS: Our findings only represent a national payer perspective. The true societal burden of long COVID in children is likely underestimated since long COVID-related indirect costs are not fully captured and access to care varies.<br><br>CONCLUSION: Children living with long COVID managed in the community pose a non-neglectable burden on French health insurance, reinforcing the importance of managing long COVID with a multidisciplinary approach and optimizing resource allocation.},
}
@article {pmid40572685,
year = {2025},
author = {Kallaste, A and Kisand, K and Aart, A and Salumets, A and Kisand, K and Peterson, P and Lember, M},
title = {Long COVID and Biomarker Dysregulation-A Shift Toward Immune Exhaustion?.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {6},
pages = {},
pmid = {40572685},
issn = {1648-9144},
mesh = {Humans ; *COVID-19/immunology/blood/complications ; Biomarkers/blood ; Male ; Female ; Middle Aged ; Longitudinal Studies ; *Cytokines/blood ; Aged ; SARS-CoV-2 ; Adult ; Inflammation ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Immune System Exhaustion ; },
abstract = {Background and Objectives: SARS-CoV-2 infection can lead to persistent or newly emerging symptoms lasting for months, a condition known as long COVID (LC). The pathophysiology of LC remains poorly understood, with cytokine dysregulation proposed as a key mechanism, although findings across the studies have been inconsistent. Materials and methods: We conducted a longitudinal study using the Olink[®] Target 96 Inflammation Panel to assess cytokines in COVID-19 (COV) patients at three months and six months post-infection. These profiles were compared with those of individuals recovering from other upper respiratory tract infections (non-COV). Additionally, we analyzed differences between individuals with LC and those who recovered from COVID-19. Predictive models for LC at three months and sixth months post-infection were developed using inflammatory markers and relevant clinical cofactors, including gender, age, BMI, hemogram, Β2-microglobulin, D-dimers, LDH, AST, ALT, Ferritin, vitamin D, CRP, and the severity of acute COVID-19 infection as classified by WHO criteria. Results: We observed a general decline in inflammatory biomarkers in post-COVID-19 patients over time, with only a few cytokines elevated (CCL4 at month 3 and CST5 at month 6) compared to non-COV controls. In LC patients, an early phase of low-grade inflammation transitioned into significant reduction in proinflammatory biomarkers compared to recovered individuals. Rather than indicating immune normalization, this pattern suggests a possible suppression or exhaustion of the immune response in the months following acute infection. Importantly, our predictive modeling demonstrated that this specific cytokine signature, in combination with acute disease severity and clinical cofactors, described well the presence of LC. Conclusions: Our findings suggest that inflammation-related biomarker dysregulation following acute SARS-CoV-2 infection evolves dynamically over a six-month period. By the sixth month, compared to the third month, the presence of LC is more accurately predicted by a combination of persistent biomarker alteration and the severity of the initial infection, as defined by WHO criteria. This represents a novel insight, as previous studies have primarily associated LC with elevated proinflammatory markers, whereas our results suggest that immune suppression or exhaustion may play a more prominent role in the later stages.},
}
@article {pmid40570227,
year = {2025},
author = {Beloglazov, VA and Yatskov, IA and Kumelsky, ED and Teslenko, MA},
title = {[Experience of using grape polyphenol concentrate in elderly patients with bronchial asthma in the post-COVID period.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {38},
number = {1},
pages = {145-149},
pmid = {40570227},
issn = {1561-9125},
mesh = {Humans ; *Vitis/chemistry ; Female ; Male ; *Asthma/drug therapy/blood ; *Polyphenols/administration &amp; dosage/therapeutic use/pharmacology ; Aged ; *COVID-19/complications ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Lipopolysaccharides/blood ; Treatment Outcome ; Middle Aged ; },
abstract = {The state of long-COVID and post-COVID syndrome is associated with the presence of low-grade inflammation (LGI) in patients, associated, among other things, with impaired permeability of natural barriers for lipopolysaccharide (LPS) of gram-negative flora. Objective - to study the effect of adding polyphenolic grape concentrate to the course of spa treatment in patients with bronchial asthma and post-covid syndrome on the state of LGI, intestinal permeability and edotoxemia. The study included 70 patients with a verified diagnosis of Bronchial asthma who had suffered from infection caused by SARS-CoV-2. Patients were divided into two groups. The intervention group (n=40) received grape polyphenol concentrate in addition to standard spa treatment. Subsequent enzyme-linked immunosorbent assay (ELISA) performed for determination of the levels of C-RP, zonulin, LPS, lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing protein (BPI). In patients of the 1st group a reliable decrease in the level of C-RP (p<0,039) and the concentration of circulating LPS (p=0,008) was revealed. In both groups, a statistically significant increase in the concentration of BPI and zonulin was registered (p<0,05). The use of polyphenolic grape concentrate in elderly patients in the post-covid period reduces the level of C-RP and circulating blood endotoxin, which in the future should reduce the likelihood of long-term consequences associated with NCI, including cardiovascular, in patients who have undergone NCI.},
}
@article {pmid40566632,
year = {2025},
author = {Chen, BK and Chan, CH and Wang, CK},
title = {Improvement on Ferrous Ion Accumulation and Mitochondrial Dysfunction in the COVID-19 Pseudovirus-Infected Cell Model Simulating the Long COVID Status by Nutritional Strategy.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
pmid = {40566632},
issn = {2075-1729},
abstract = {The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerged various mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID (LC), lasting up to 12 weeks or even longer. The mechanism has yet to be clarified. COVID-19 pseudovirus is a suitable model to understand the infection of the COVID-19 virus to cells, which is suitable to see the acute change in cells owing to its one-time infection and inactivation. The ACE2-293T cell infected by COVID-19 pseudovirus was used in this study. After the infection and removal of the pseudovirus, high amounts of ferrous ions were accumulated in mitochondria and then released into the cytosol. Reactive oxygen species (ROS) accumulation was formed and caused mitochondrial dysfunction. To evaluate the effect of nutritional strategy on ferrous ion accumulation and mitochondrial dysfunction, lactoferrin, Q10 and Echinacea purpurea extract (EPE) were used in this study. Results showed that lactoferrin, Q10 and EPE could improve mitochondrial dysfunction by reducing the accumulation of ferrous ions and ROS in the mitochondria. HPLC analysis showed that EPE contained rich caffeic acid, and it also showed perfect improvement in mitochondrial dysfunction. In conclusion, cells infected with pseudovirus could increase the accumulation of ferrous ions and ROS in mitochondria and be released into the cytosol after removing pseudovirus, thereby causing mitochondrial dysfunction. Lactoferrin, Q10 and EPE were an effective nutritional strategy to suppress ferrous ion accumulation, ROS formation and advanced mitochondrial dysfunction.},
}
@article {pmid40566540,
year = {2025},
author = {Koutsiaris, AG and Karakousis, K},
title = {Long COVID Mechanisms, Microvascular Effects, and Evaluation Based on Incidence.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
pmid = {40566540},
issn = {2075-1729},
abstract = {Since the initial reports of Long COVID symptoms, numerous pathophysiological mechanisms have been proposed to explain them; nevertheless, no consensus has been reached. Some of these mechanisms are directly linked to microcirculation, while others are related indirectly. Those with a direct connection involve the respiratory system (such as pulmonary embolism), the cardiovascular system (including cardiac arrest, heart failure, myocardial inflammation, stroke, endothelial dysfunction, and microangiopathy), hematological conditions (like coagulopathy, deep vein thrombosis, microclots, and endothelial irregularities), and brain function. However, few of these mechanisms are grounded in quantitative data and fundamental physiological principles. Furthermore, diagnostic and therapeutic methods remain inadequate. This report provides a brief overview of these processes, focusing primarily on quantitative data, recently proposed mechanisms, and advances in microcirculation, with a special emphasis on the tissue blood supply reduction (TBSR or SR in short) mechanism. Then, the SR pathophysiological mechanism is assessed based on the total incidence rate of the Long COVID symptoms that can be directly attributed to this mechanism. The proposed SR mechanism can account for seven principal Long COVID symptoms with a total normalized incidence of 76%.},
}
@article {pmid40566294,
year = {2025},
author = {Rocha, DM and Pedroso, AO and Menegueti, MG and Silveira, RCCP and Sousa, LRM and Gir, E and Reis, RK},
title = {Predictors of Anxiety, Depression, and Stress in Long COVID: Systematic Review of Prevalence.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {6},
pages = {},
pmid = {40566294},
issn = {1660-4601},
support = {88881.657963/2021-01//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Anxiety/epidemiology/etiology ; *Depression/epidemiology/etiology ; Prevalence ; *Stress, Psychological/epidemiology/etiology ; Aged ; SARS-CoV-2 ; Adult ; },
abstract = {Anxiety, depression, and stress are prevalent psychosocial manifestations in Long COVID, and understanding their global impact can guide safe, effective, and evidence-based interventions. This study reviewed the literature to analyze the prevalence indicators and predictors of anxiety, depression, or stress experienced by adults and older adults with Long COVID. This systematic prevalence review was conducted using the databases MEDLINE via PubMed[®], CINAHL-EBSCO, Web of Science, Scopus, EMBASE, LILACS, and BDENF. Observational studies that assessed anxiety, depression, or perceived stress in adults and older adults with Long COVID were included, with no restrictions on time or language. Two reviewers independently conducted the selection process. Full texts were analyzed for their eligibility potential. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Studies. Ten observational studies with moderate methodological quality were included. Anxiety and depression were the most prevalent psychosocial symptoms in Long COVID, reported in mild, moderate, and severe cases of COVID-19 infection. Prevalence rates reached up to 47.8% for anxiety, 37.3% for depression, and 23% for stress. The combined analysis revealed a pooled prevalence of 15.3% (95% CI: 10.8% to 20.2%). Being female, having pre-existing mental disorders or associated clinical comorbidities, experiencing severe infection in the acute phase, and receiving intensive care were predictors of greater mental burden. The experience of anxiety, depression, and stress in prolonged COVID-19 was reported in countries with different income levels and was disproportionately experienced, especially by women and individuals with associated clinical conditions or psychopathological comorbidities.},
}
@article {pmid40565969,
year = {2025},
author = {Chynkiamis, N and Vontetsianos, A and Anagnostopoulou, C and Lekka, C and Gounaridi, MI and Oikonomou, E and Vavuranakis, M and Rovina, N and Bakakos, P and Koulouris, N and Kaltsakas, G and Vogiatzis, I},
title = {Hybrid Pulmonary Rehabilitation Improves Cardiorespiratory Exercise Fitness in Formerly Hospitalised Long COVID Patients.},
journal = {Journal of clinical medicine},
volume = {14},
number = {12},
pages = {},
pmid = {40565969},
issn = {2077-0383},
abstract = {Background/Objectives: Supervised pulmonary rehabilitation (PR) is effective in improving cardiorespiratory fitness in non-hospitalised individuals with long COVID. However, there is limited evidence regarding PR-induced improvements in cardiorespiratory parameters in previously hospitalised COVID-19 survivors. This study aimed to investigate the effect of a hybrid PR programme (outpatient followed by a digital intervention) on exercise tolerance, cardiorespiratory adaptations, functional capacity and quality of life outcomes in previously hospitalised COVID-19 survivors. Methods: Forty-two patients (age (mean ± SD): 57 ± 12 yrs) with excessive fatigue due to long COVID (FACIT score (26 ± 10) were allocated to PR (n = 27) or usual care (UC) (n = 15) 140 ± 75 days from hospital discharge. PR consisted of 8 outpatient sessions (twice weekly for 4 weeks) followed by 24 home-based sessions (3 times/week for 8 weeks). Patients in the UC group were instructed to be physically active. Exercise tolerance was assessed by cardiopulmonary cycling testing to the limit of tolerance. Results: Following the completion of the hybrid PR programme, peak work rate (WRpeak) and peak oxygen uptake (VO2peak) were, respectively, improved in the PR group by 19 ± 10 Watt (p = 0.001) and by 2.4 ± 3.0 mL/kg/min (p = 0.001). Furthermore, in the PR group, the 6 min walk distance was increased by 72 ± 69 metres (p = 0.001). FACIT and mMRC scores were also improved in the PR group by 15 ± 10 (p = 0.001) and by 1.4 ± 1.0 (p = 0.001), respectively. In the UC group, only the mMRC score was improved by 0.7 ± 1.0 (p = 0.008). Conclusions: The application of a hybrid PR programme was beneficial in improving cardiorespiratory exercise fitness, functional capacity and quality of life in previously hospitalised COVID-19 survivors.},
}
@article {pmid40565006,
year = {2025},
author = {Coelho, SVA and Souza, GLE and Bezerra, BB and Lima, LR and Correa, IA and de Almeida, DV and Silva-Aguiar, RPD and Pinheiro, AAS and Sirois, P and Caruso-Neves, C and Costa, LJD and Scharfstein, J and Arruda, LB},
title = {SARS-Cov-2 Replication in a Blood-Brain Barrier Model Established with Human Brain Microvascular Endothelial Cells Induces Permeability and Disables ACE2-Dependent Regulation of Bradykinin B1 Receptor.},
journal = {International journal of molecular sciences},
volume = {26},
number = {12},
pages = {},
pmid = {40565006},
issn = {1422-0067},
support = {(01.20.0029.000462/20 404096/2020-4; 01.22.0074.00 (1227/21))//Rede Corona-&#xf4;mica BR MCTI/FINEP affiliated to RedeV&#xed;rus/MCTI/ ; CAPES//Coordination for the Improvement of Higher Education Personnel/ ; CNPq//Brazilian National Council for Scientific and Technological Development/ ; FAPERJ; 740 LBA E-26/201.206/2021, E-26/204.307/2024; JS E-26/ 210.059/ 2020, and E-26/210.251/-2020 and E-741 26/201.062/2021; SVAC E-26/20.746/2022; BBB E-26/202.346/2024; LRL E-26/201.918/2024//Carlos Chagas Filho Research Support Foundation/ ; },
mesh = {Humans ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; *Blood-Brain Barrier/virology/metabolism/pathology ; *SARS-CoV-2/physiology ; *Receptor, Bradykinin B1/metabolism ; *Endothelial Cells/metabolism/virology ; *COVID-19/metabolism/virology/pathology ; *Virus Replication ; Bradykinin/metabolism/analogs &amp; derivatives ; Brain/blood supply/metabolism ; Capillary Permeability ; Microvessels ; },
abstract = {Endothelial dysfunction plays a central role in COVID-19 pathogenesis, by affecting vascular homeostasis and worsening thromboinflammation. This imbalance may contribute to blood-brain barrier (BBB) disruption, which has been reported in long COVID-19 patients with neurological sequelae. The kallikrein-kinin system (KKS) generates bradykinin (BK), a proinflammatory peptide that induces microvascular leakage via B2R. Under inflammatory conditions, BK is converted to Des-Arg-BK (DABK), which activates B1R, a receptor upregulated in inflamed tissues. DABK is degraded by ACE2, the main SARS-CoV-2 receptor; thus, viral binding and ACE2 downregulation may lead to DABK/B1R imbalance. Here, we investigated these interactions using human brain microvascular endothelial cells (HBMECs), as a model of the BBB. Since endothelial cell lines express low levels of ACE2, HBMECs were modified with an ACE2-carrying pseudovirus. SARS-CoV-2 replication was confirmed by RNA, protein expression, and infectious particles release. Infection upregulated cytokines and endothelial permeability, enhancing viral and leukocyte transmigration. Additionally, viral replication impaired ACE2 function in HBMECs, amplifying the response to DABK, increasing nitric oxide (NO) production, and further disrupting endothelial integrity. Our findings reveal a mechanism by which SARS-CoV-2 impacts the BBB and highlights the ACE2/KKS/B1R axis as a potential contributor to long COVID-19 neurological symptoms.},
}
@article {pmid40564201,
year = {2025},
author = {Hemat Jouy, S and Tonchev, H and Mostafa, SM and Mahmoud, AM},
title = {Post-COVID Metabolic Fallout: A Growing Threat of New-Onset and Exacerbated Diabetes.},
journal = {Biomedicines},
volume = {13},
number = {6},
pages = {},
pmid = {40564201},
issn = {2227-9059},
support = {R00 HL140049/HL/NHLBI NIH HHS/United States ; R01 HL161386/HL/NHLBI NIH HHS/United States ; 1R00HL140049-03/NH/NIH HHS/United States ; 1R01HL161386-04/NH/NIH HHS/United States ; },
abstract = {Emerging evidence highlights the profound and lasting impact of severe illnesses such as COVID-19, particularly among individuals with underlying comorbidities. Patients with pre-existing conditions like diabetes mellitus (DM) are disproportionately affected, facing heightened risks of both disease exacerbation and the onset of new complications. Notably, the convergence of advanced age and DM has been consistently associated with poor COVID-19 outcomes. However, the long-term metabolic consequences of SARS-CoV-2 infection, especially its role in disrupting glucose homeostasis and potentially triggering or worsening DM, remain incompletely understood. This review synthesizes current clinical and experimental findings to clarify the bidirectional relationship between COVID-19 and diabetes. We critically examine literature reporting deterioration of glycemic control, onset of hyperglycemia in previously non-diabetic individuals, and worsening of metabolic parameters in diabetic patients after infection. Furthermore, we explore proposed mechanistic pathways, including pancreatic β-cell dysfunction, systemic inflammation, and immune-mediated damage, that may underpin the development or progression of DM in the post-COVID setting. Collectively, this work underscores the urgent need for continued research and clinical vigilance in managing metabolic health in COVID-19 survivors.},
}
@article {pmid40564133,
year = {2025},
author = {Pisaturo, M and Russo, A and Grimaldi, P and Monari, C and Imbriani, S and Gjeloshi, K and Ricozzi, C and Astorri, R and Curatolo, C and Palladino, R and Caruso, F and Ambrisi, F and Onorato, L and Coppola, N},
title = {Prevalence, Evolution and Prognostic Factors of PASC in a Cohort of Patients Discharged from a COVID Unit.},
journal = {Biomedicines},
volume = {13},
number = {6},
pages = {},
pmid = {40564133},
issn = {2227-9059},
support = {CUP: I83C22001810007//Regione Campania/ ; },
abstract = {Background and Aim: PASC is a potentially debilitating clinical condition consisting of different general symptoms experienced by about 10% of patients with previous SARS-CoV-2 infection. Our study analyses a cohort of patients with a history of hospitalization for COVID-19 and aims to evaluate prognostic factors for experiencing PASC and to investigate the characteristics of patients experiencing PASC symptoms. Methods: This is an observational, monocentric retrospective study including all adult patients admitted to our COVID unit from 28 February 2020 to 30 April 2022, discharged alive, and having performed at least one follow-up visit at our post-COVID outpatient clinic after a minimum of three months from discharge. Patients who experienced persistent clinical manifestations or the development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation, were defined as having PASC. Results: A total of 429 patients were discharged alive from our COVID Unit and 244 patients performed at least one follow-up visit in our outpatient clinic. Of these, 134 patients did not experience PASC, while 110 patients experienced PASC. Long-COVID patients were more frequently female (43.6% vs. 31.3%, p = 0.048), more frequently presented throat pain and headache at hospital admission (respectively 8.9% vs. 2.5%, p = 0.041 and 15.8% vs. 5%, p = 0.007), and were more likely to have a history of type 2 diabetes mellitus (25.5% vs. 13%, p =0.013). At the multivariable analysis, female gender, type 2 diabetes, and headache at admission were factors associated with PASC. All 46 patients who performed at least two different admissions in our outpatient clinic were divided in two groups: the first including the 16 patients who experienced a reduction or a resolution of symptoms related to COVID-19, the second comprising the 30 patients who experienced clinical worsening or persisting symptoms. Smoking habit was more represented among patients with stable or worsening symptoms (42.3% vs. 7.7%, p = 0.042); myalgias at admission were more frequent in the clinical worsening group (27.6% vs. 0%, p= 0.039); and a larger amount of patients who reported neuropsychiatric symptoms and respiratory symptoms were in the stable or worsening PASC symptoms group. Discussion: In conclusion, this study underscores the complexity of PASC, identifying female sex, Type 2 diabetes, and certain acute COVID-19 symptoms as potential predisposing factors for its development. PASC still represents a substantial public health challenge, and ongoing efforts are essential to better understand its underlying mechanisms and improve patient outcomes.},
}
@article {pmid40563736,
year = {2025},
author = {Doskas, T and Vavougios, GD and Kormas, C and Kokkotis, C and Tsiptsios, D and Spiliopoulos, KC and Tsiakiri, A and Christidi, F and Aravidou, T and Dekavallas, L and Kazis, D and Dardiotis, E and Vadikolias, K},
title = {Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer's Disease.},
journal = {Brain sciences},
volume = {15},
number = {6},
pages = {},
pmid = {40563736},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: SARS-CoV-2 can affect the central nervous system directly or indirectly. AD shares several similarities with long COVID cognitive impairment on a molecular and imaging level, as well as common risk factors. The objective of this review is to evaluate the incidence of post-acute COVID-19 cognitive impairment. Secondarily, we aim to determine if neuroinflammation in COVID-19 survivors may be associated with the onset of neurological disease, with a focus on Alzheimer's disease (AD).<br><br>METHODS: literature search up to March 2025 on the prevalence of cognitive deficits in COVID-19 survivors, underlying pathophysiology and associations with neurological disorders.<br><br>RESULTS: a wide array of neuropsychiatric manifestations is associated with COVID-19; executive function, memory, and attention are the most frequently reported neurocognitive deficits, regardless of COVID-19 severity. There are associations between the risks for cognitive deficits post-infection with the age of the patients and the severity of the disease. Increasing evidence suggests that neurocognitive deficits are associated with the onset of neurological and neuropsychiatric disease in COVID-19 survivors.<br><br>CONCLUSIONS: clinicians caring for COVID-19 survivors should actively investigate neurocognitive sequelae, particularly for patients with increased risk for cognitive deficits.},
}
@article {pmid40561297,
year = {2025},
author = {Alves, NS and Silva, END and Melo, GBT and Paulino, MAS and Angulo-Tuesta, A},
title = {Agenda for COVID-19 and long COVID research priorities in Brazil: results of wide consultation and Delphi consensus, 2022-2023.},
journal = {Epidemiologia e servicos de saude : revista do Sistema Unico de Saude do Brasil},
volume = {34},
number = {},
pages = {e20240623},
pmid = {40561297},
issn = {2237-9622},
mesh = {Brazil/epidemiology ; Humans ; *COVID-19/epidemiology ; Delphi Technique ; Consensus ; *Research/organization &amp; administration ; Qualitative Research ; *Biomedical Research ; },
abstract = {OBJECTIVE: To propose an agenda of COVID-19 and long COVID research priorities, in order to guide government and research funding agencies to optimize health science, technology and innovation resources in Brazil.<br><br>METHODS: This is a qualitative study, carried out in two stages, between April 2022 and March 2023. In the first stage, a broad consultation was carried out to identify research priorities according to the axes of the COVID-19 Evidence Network to support Decision-making initiative, with 71 participants including researchers, health service managers, health science and technology managers, health professionals and health service users. In the second stage, a consensus was reached on the priorities proposed in the previous stage, using the Delphi method, with a panel of 20 experts on COVID-19 in the first round and 18 in the second round.<br><br>RESULTS: In the broad consultation, 186 priority lines of research on COVID-19 were received and consolidated into 161 research lines. Of these, 139 achieved consensus in the first round of the Delphi method, and a further 40 lines were received and included in the second round for consensus. The proposed agenda has 179 research lines on COVID-19. The predominant themes were evaluation, COVID-19 impact and sequelae, long COVID-19, mental illnesses and immunosuppression. The child population was of greatest interest.<br><br>CONCLUSIONS: This study demonstrated high levels of agreement among participants on COVID-19 and long COVID research priorities in Brazil.},
}
@article {pmid40560299,
year = {2025},
author = {Hung, CT and Hung, YC and Suk, CW and Wu, CH},
title = {Evaluating the associations among asthma, asthma control and long COVID in U.S. adults.},
journal = {Infection},
volume = {53},
number = {6},
pages = {2523-2531},
pmid = {40560299},
issn = {1439-0973},
mesh = {Humans ; *Asthma/epidemiology/complications ; *COVID-19/epidemiology/complications ; Adult ; Male ; Female ; Middle Aged ; United States/epidemiology ; Prevalence ; Aged ; Young Adult ; SARS-CoV-2 ; Adolescent ; Severity of Illness Index ; Emergency Service, Hospital/statistics &amp; numerical data ; Risk Factors ; },
abstract = {OBJECTIVE: This study aimed to evaluate (1) the association between asthma and long COVID among U.S. adults and (2) the association between asthma control and long COVID among U.S. adults with asthma.<br><br>METHODS: Data from the 2023 National Health Interview Survey were used. Adults aged&#x2009;&#x2265;&#x2009;18 years were included. Asthma control was measured by the history of asthma attacks and emergency room (ER) visits for asthma. Multivariable logistic regression models were used to evaluate the associations. A sensitivity analysis was performed by stratifying long COVID severity.<br><br>RESULTS: A total of 258,237,552 adults were included in this study. The prevalence of long COVID among U.S. adults in 2023 was 8.2%. When stratified by the presence of asthma, the prevalence was 15.2% for those with asthma and 7.6% for those without asthma (P&#x2009;<&#x2009;0.01). After adjusting for covariates, adults with asthma had higher odds of long COVID than those without asthma (OR, 1.58; 95% CI, 1.37-1.83). This association was consistent across long COVID severity levels. Poor asthma control was associated with increased odds of long COVID (asthma attacks: OR, 1.47; 95% CI, 1.09-1.97; ER visits for asthma: OR, 1.52; 95% CI, 1.02-2.27).<br><br>CONCLUSION: Asthma was associated with increased odds of long COVID. Patients with poorly controlled asthma were associated with increased odds of long COVID. From a clinical perspective, it is crucial to proactively identify patients with asthma at increased risk of long COVID, especially those with certain comorbidities. Future research on specific symptoms and the duration of long COVID among patients with asthma will benefit clinical practice.},
}
@article {pmid40559200,
year = {2025},
author = {Cianciulli, A and Santoro, E and Manente, R and Pacifico, A and Comunale, G and Finizio, M and Capunzo, M and De Caro, F and Franci, G and Moccia, G and Boccia, G},
title = {Validation of a Questionnaire on the Post-COVID-19 Condition (Long COVID): A Cross-Sectional Study in Italy.},
journal = {Infectious disease reports},
volume = {17},
number = {3},
pages = {},
pmid = {40559200},
issn = {2036-7430},
abstract = {BACKGROUND/OBJECTIVES: Long COVID is a condition that was initially recognized by social support groups, and later by the scientific and medical communities. It affects COVID-19 survivors at various levels of severity, including young people, children and non-hospitalized people. Although the exact definition is unclear, the most common symptoms are fatigue and shortness of breath, which persist for months. Other symptoms include cognitive impairment, pain, palpitations, and gastrointestinal and heart problems. This study evaluated the reliability and validity of a questionnaire designed to examine the development and effects of long COVID.<br><br>METHODS: A questionnaire, composed of three sections, with a total of 24 items, was administered to subjects who had recovered from the COVID-19 disease in Italy. Data were collected from February to April 2025, and a statistical analysis was performed using R[&#xae;] statistical software for Windows, version 4.3.3. Cronbach's alpha was tested to check internal consistency. The questionnaire was completed voluntarily and anonymously by 250 individuals who had recovered from the SARS-CoV-2 infection. The questionnaire was self-administered and had open and structured questions.<br><br>RESULTS: The highest value of Cronbach's alpha was found on 18 items (alpha = 0.97), which means that the questionnaire has satisfactory internal validity.<br><br>CONCLUSIONS: This study highlights and confirms the continuity of symptoms manifested during the acute phase of the SARS-CoV-2 infection in the post-COVID-19 phase and the significant impact of these symptoms on daily life activities. Given its excellent reliability properties and high internal consistency, the instrument is recommended for future longitudinal studies and with large cohorts in order to carry out valid and replicable measurements of COVID-19 symptomatology.},
}
@article {pmid40559080,
year = {2025},
author = {Miana, M and Moreta-Fuentes, R and Jiménez-Antona, C and Moreta-Fuentes, C and Laguarta-Val, S},
title = {Improvement of Fatigue and Body Composition in Women with Long COVID After Non-Aerobic Therapeutic Exercise Program.},
journal = {Journal of personalized medicine},
volume = {15},
number = {6},
pages = {},
pmid = {40559080},
issn = {2075-4426},
support = {II PI 2021/05//illustrious professional association of physiotherapists of the community of Madrid/ ; },
abstract = {Background/Objective: Fatigue is one of the most recurrent and most disabling symptoms of long COVID (LC) and is associated with a worse quality of life. Reducing body fat in these patients could be important to mitigate fatigue and post-exertional worsening. Aerobic exercise may not be indicated in LC patients who have orthostatic tachycardia and post-exertional worsening. The aim of this study was to evaluate the effects of a personalized supine therapeutic motor control exercise program on fatigue and fat tissue in women with LC. Methods: A single-arm exploratory case study, with a pre-post format, was conducted on 17 women with LC to test the effects of a plank-based strengthening exercise program on fatigue, which was evaluated by the Modified Fatigue Impact Scale and fat tissue assessed by bioimpedance. The twelve-week program included two weekly sessions. The exercise program was personalized, considering the symptoms and characteristics of the patients. Results: Participants with overweight or obesity (n = 12) comprised 70% of the entire sample. After completing the exercise program this value decreased by 5.9 percentage points. Significant differences were found in the total [(MD = -1.72, 95% CI -2.57 to -0.86), r = 0.73], trunk, upper and inner limbs body fat percentages (p < 0.05). The overall fatigue decreased at 12 weeks [(MD = -14.00, 95% CI -21.69 to -6.31), r = 0.69] as well as the physical and psychosocial fatigue sub-scale (p < 0.001); no differences were observed in the cognitive sub-scale. Conclusions: The plank-based personalized strengthening exercise program showed rapid improvements in fatigue and fat percentages. It could be an effective strategy to achieve improvements for LC patients.},
}
@article {pmid40557167,
year = {2025},
author = {Ćwilichowska-Puślecka, N and Makowiecka, A and Kalinka, M and Groborz, K and Puślecki, T and Drąg, M and Simon, K and Dąbrowska, K and Pazgan-Simon, M and Poręba, M},
title = {Understanding the long-term interplay of SARS-CoV-2 immune and inflammatory responses with proteases in COVID-19 recovery: a longitudinal study.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1517933},
pmid = {40557167},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; Longitudinal Studies ; *SARS-CoV-2/immunology ; Male ; Middle Aged ; Female ; *Peptide Hydrolases/immunology/blood/metabolism ; Adult ; Inflammation/immunology ; Aged ; Cytokines/blood/immunology ; Convalescence ; },
abstract = {INTRODUCTION: The immune and inflammatory responses following SARS-CoV-2 infection, particularly in the context of long COVID, remain critical areas of study. Understanding these responses is essential for addressing the long-term health impacts of COVID-19. Recent research also highlights the pivotal role of proteases in modulating immune responses and contributing to disease severity, making them a key focus of our analysis.<br><br>METHODS: We conducted a longitudinal analysis of 72 convalescent COVID-19 patients, assessing recovery at three key time points: immediately post-discharge, one month later, and three months post-infection. Additionally, a subset of 15 patients was followed up two years post-COVID-19. Clinical parameters, including demographics, comorbidities, treatment modalities, and COVID-19 severity, were evaluated. Using CyTOF technology, we characterized over 30 immune cell subsets, including granulocytes, T cells, B cells, NK cells, and monocytes. We also performed multiplexed analyses of blood samples to profile&#xa0;cytokines, chemokines, growth factors, proteases, and COVID-19-related proteins.<br><br>RESULTS: Our comprehensive approach revealed significant changes in the immune system over time, highlighting the role of specific immune cells and proteases in the recovery process. Key findings include a decreasing deregulatory effect on immune responses exerted by subsequent SARS-CoV-2 variants Alpha, Delta, and Omicron.<br><br>CONCLUSION: This study provides an in-depth understanding of the molecular dynamics of immune recovery following COVID-19. By integrating clinical profiling, plasma multiplex analysis, antibody profiling, mass cytometry immunophenotyping, in vitro PBMC stimulation, and the role of proteases, we offer valuable insights into the complex interplay of immune, inflammatory, and protease-mediated responses in individuals recovering from COVID-19.},
}
@article {pmid40556843,
year = {2025},
author = {Ojha, A and Bhasin, M and Agni, MB and Gowda, KD},
title = {Serum ferritin as a predictive marker of pulmonary fibrosis in post-COVID-19.},
journal = {Qatar medical journal},
volume = {2025},
number = {2},
pages = {44},
pmid = {40556843},
issn = {0253-8253},
abstract = {BACKGROUND: Pulmonary fibrosis is characterized by excessive matrix formation, which destroys typical lung architecture and increases the chances of comorbidity. It is essential to look into potential serum indicators for the early identification of individuals who may develop such severe fibrotic consequences since there is currently no specific marker for the early diagnosis of post-COVID-19 pulmonary fibrosis. The study is aimed at examining potential serum markers that could be used for early detection of pulmonary fibrosis in patients with COVID-19.<br><br>METHODS: It is a cross-sectional retrospective observational study that included male (n = 26) and female (n = 10) patients who were confirmed positive for COVID-19 using the Reverse transcription polymerase chain reaction (RTPCR) test. Various hematological parameters, such as platelet count, white blood cell count (WBC count), platelet-to-lymphocyte ratio (PLR), white blood cell count to mean platelet volume ratio (WMR), red cell distribution width (RDW), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), serum ferritin level, and CT severity scores (CT-SSs) were recorded. The association between hematological parameters, serum ferritin level, and CT-SS was assessed by the Pearson correlation test using the GraphPad Prism software (version 10). p < 0.05 was considered statistically significant.<br><br>RESULTS: The descriptive analysis revealed no significant correlation between platelet count (r = 0.1610, p = 0.3483), WBC count (r = -0.1381, p = 0.4217), PLR (r = 0.2262, p = 0.1847), WMR (r = -0.1093, p = 0.5258), RDW (r = 0.05982, p = 0.7289), PCT (r = -0.059, p = 0.752), MPV (r = 0.046, p = 0.788), and PDW (r = -0.06, p = 0.699) with CT-SS. However, a significant positive correlation was observed between CT-SS and serum ferritin levels in COVID-19 patients (r = 0.5452, p = 0.0006).<br><br>CONCLUSIONS: As there was a significant positive correlation between serum ferritin level and CT-SS, the serum ferritin level could be considered as a simple and cost-effective biomarker for predicting the development of lung fibrosis in long COVID-19 conditions after controlling the confounders.},
}
@article {pmid40554922,
year = {2025},
author = {Weinerova, J and Yeung, S and Guo, P and Yau, A and Horne, C and Ghinn, M and Curtis, L and Adlard, F and Bhagat, V and Zhang, S and Kaser, M and Bozic, M and Schluppeck, D and Reid, A and Tibon, R and Cheke, L},
title = {Changes in memory function in adults following SARS-CoV-2 infection: Findings from the Covid and Cognition online study.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {189},
number = {},
pages = {205-225},
doi = {10.1016/j.cortex.2025.05.019},
pmid = {40554922},
issn = {1973-8102},
mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Adult ; *Cognition/physiology ; Middle Aged ; Reaction Time/physiology ; SARS-CoV-2 ; Neuropsychological Tests ; Aged ; Young Adult ; *Memory/physiology ; *Memory, Long-Term/physiology ; },
abstract = {SARS-CoV-2, the virus responsible for the Covid-19 pandemic, has been shown to have an impact on cognitive function, but the specific aspects of cognition that are affected remain unclear. In this Registered Report, we analysed cognitive data collected online from 296 participants (209 who had experienced Covid-19 infection and 87 who did not). We have found previously reported effect of Covid status on accuracy in 2 long-term memory tasks (verbal item memory task and nonverbal associative memory task), but did not replicate previously reported effect on reaction times. Further, across 4 long-term memory tasks, we found consistent effect of Covid status on memory accuracy but not reaction times. Contrary to our predictions, we did not find an interaction with memory type (associative versus item) or stimulus type (verbal versus nonverbal). Moreover, we compared cognitive functioning amongst vaccinated and unvaccinated individuals to explore the role of vaccination status in cognitive symptoms associated with Covid-19. Using Bayesian analysis, we did not find conclusive evidence for either the null or alternative hypothesis. Overall, the study replicates and extends previously reported findings, thereby providing valuable insights into the effects of SARS-CoV-2 infection on cognitive functions.},
}
@article {pmid40554575,
year = {2025},
author = {Vallée, G and Xi, D and Avramovic, G and O'Kelly, B and Lambert, JS},
title = {Evaluating the longitudinal physical and psychological health effects of persistent long Covid 3.5 years after infection.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0326790},
pmid = {40554575},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Adult ; *Mental Health ; SARS-CoV-2/isolation &amp; purification ; Aged ; Anxiety ; Surveys and Questionnaires ; Fatigue ; },
abstract = {This is a 3.5-year single-center observational cohort study investigating the longitudinal impact of Long Covid on the physical and mental health of patients. Patients were assessed at 3 months, 1 year, and 3.5-years post-infection using the 12-item Short Form Survey, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 scale and the Impact of Events Scale-Revised questionnaire. Additionally, a clinical symptom review was conducted for patients with persistent Long Covid at the 3.5-year follow-up. We had 149 respondents at 3 months, 94 at 1 year and 85 at 3.5-year. Of those who participated, 72% had Long Covid at the 3-month follow-up, with 26% and 25% having persistence of Long Covid symptoms at 1-year and 3.5 years, respectively. The most reported symptoms at the 3.5-year timepoint included fatigue, difficulty sleeping and easy crashing following activities. Overall, patients' Physical Composite Scores significantly improved between the 3-month and 3.5-year timepoints. However, the Physical Composite Scores of patients with persistent Long Covid were significantly lower than those of non-Long Covid patients at both the 3-month and 1-year follow-ups. The Mental Composite Score of persistent Long Covid patients remained significantly lower than individuals without Long Covid at all timepoints. At 3 months, Long Covid disproportionately met the criteria for depression, anxiety and PTSD symptoms. At 1 and 3.5 years, patients with persistent Long Covid were more likely to meet the criteria for depressive symptoms than those without Long Covid. Between the 3-months and 3.5-year timepoints, there was a significant reduction in the number of patients with persistent Long Covid who met the criteria for PTSD and anxiety symptoms. Although patients with Long Covid for 3.5 years had shown improvements in both their physical and mental health over time, they continue to lag behind those without Long Covid.},
}
@article {pmid40552782,
year = {2025},
author = {Xu, Y and Xu, JW and Wu, Y and Rong, LJ and Ye, L and Franco, OH and Chien, CW and Feng, XR and Chen, JY and Tung, TH},
title = {Prevalence and prognosis of sarcopenia in acute COVID-19 and long COVID: a systematic review and meta-analysis.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2519678},
pmid = {40552782},
issn = {1365-2060},
mesh = {Humans ; *Sarcopenia/epidemiology ; *COVID-19/complications/epidemiology/mortality ; Prevalence ; Prognosis ; SARS-CoV-2 ; Length of Stay/statistics &amp; numerical data ; Hospitalization/statistics &amp; numerical data ; },
abstract = {BACKGROUND: A comprehensive investigation delineating the prevalence of sarcopenia across different infection phases, from acute COVID-19 to long COVID, is lacking. Meanwhile, the relationship between sarcopenia and adverse outcomes among COVID-19 patients remains inconsistent.<br><br>MATERIALS AND METHODS: A systematic search of MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus, before 22nd February 2025, was conducted to identify studies assessing sarcopenia prevalence in acute COVID-19 and long COVID. Random effects meta-analyses were performed to estimate the pooled prevalence of sarcopenia for acute COVID-19 and long COVID patients. Subgroup analyses stratified by assessment tool, region, income, hospitalization status, and age were performed. The associations between sarcopenia and COVID-19-related clinical outcomes were further quantified.<br><br>RESULTS: A total of 39 studies with 6,982 individuals were included. The pooled prevalence of sarcopenia was 48.7% (95% confidence interval (CI): 39.6-57.9%) in acute COVID-19 and 23.5% (95% CI: 12.7-39.4%) in long COVID. In acute COVID-19 patients, sarcopenia was not significantly associated with length of stay (mean difference = 2.215, 95% CI: -0.004 to 4.433), mechanical ventilation (Odds ratio (OR) = 1.80, 95% CI: 0.84-3.85), admission to the intensive care unit (OR = 1.05, 95% CI: 0.63-1.77), or mortality (OR = 1.41, 95% CI: 0.86-2.32), but was significantly associated with tracheostomy (OR = 2.48, 95% CI: 1.28-4.82).<br><br>CONCLUSION: In conclusion, our findings indicate that sarcopenia is highly prevalent in acute COVID-19 and persists in a substantial proportion of long COVID patients, suggesting prolonged muscle loss beyond the acute phase. Future well-designed studies are needed to further investigate the association between sarcopenia and short-term and long-term prognostic outcomes in both acute and long COVID patients.},
}
@article {pmid40549427,
year = {2025},
author = {Luo, X and Li, Y and Xu, J and Zheng, Z and Ying, F and Huang, G},
title = {AI in Medical Questionnaires: Scoping Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e72398},
pmid = {40549427},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Surveys and Questionnaires ; COVID-19/epidemiology ; *Mental Disorders/diagnosis ; SARS-CoV-2 ; },
abstract = {UNLABELLED: This systematic review aimed to explore the current applications, potential benefits, and issues of artificial intelligence (AI) in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe. The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. AI technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis. To systematically assess the value of AI in medical questionnaires, this study searched 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure) for the period from database inception to September 2024. Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed significant advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems. In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.<br><br>BACKGROUND: The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. Artificial Intelligence (AI) technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis.<br><br>OBJECTIVE: This review aimed to explore the current applications, potential benefits, and issues of AI in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe.<br><br>METHODS: The review included peer-reviewed studies that applied AI technologies to medical, psychological, or physiological questionnaires and reported measurable outcomes; non&#x2013;peer-reviewed, non-English/Chinese, ethically noncompliant, or AI-unrelated studies were excluded. Five databases (PubMed, Embase, Cochrane Library, Web of Science, and CNKI) were searched from inception through September 2024. Three independent reviewers conducted data extraction, quality appraisal using the Joanna Briggs Institute tools, and narrative synthesis of AI applications across questionnaire assessment, development, and prediction tasks.<br><br>RESULTS: Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems.<br><br>CONCLUSIONS: In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.},
}
@article {pmid40548547,
year = {2025},
author = {Boutet, M and Salmam, I and Roy, JS and Best, K and Perreault, K and Desmeules, F and Campeau-Lecours, A and Beaulieu-Bonneau, S},
title = {Cognitive and psychological functioning in individuals with long COVID: a comparative cross-sectional study.},
journal = {Disability and rehabilitation},
volume = {47},
number = {26},
pages = {6881-6888},
doi = {10.1080/09638288.2025.2521000},
pmid = {40548547},
issn = {1464-5165},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Quality of Life ; *COVID-19/psychology/complications ; Middle Aged ; Anxiety/psychology ; Adult ; Depression/psychology ; Neuropsychological Tests ; *Cognition ; SARS-CoV-2 ; Aged ; Post-Acute COVID-19 Syndrome ; Self Report ; *Cognitive Dysfunction ; },
abstract = {PURPOSE: Although several studies have examined cognitive and psychological functioning in long COVID, few have included appropriate comparison groups and utilized both subjective and objective measures. First, this study compared objective cognitive performance and self-reported cognitive and psychological symptoms across individuals with long COVID, those recovered without persistent symptoms, and a Control Group with no history of COVID-19 infection. Second, the relationship between sociodemographic and disease characteristics and cognitive and psychological outcomes was explored in the Long COVID Group (LCG). Third, the association between cognitive and psychological outcomes and quality of life was examined in the LCG.<br><br>METHODS: Participants included 120 adults per group. The main outcome measures were three neuropsychological tests and self-report questionnaires on cognitive functioning, anxiety, depression, and quality of life.<br><br>RESULTS: Individuals with long COVID exhibited poorer attention and working memory performance, and reported higher cognitive, anxiety, and depression symptoms compared to the other groups. Within the LCG, better cognitive performance on a screening test and higher depressive symptoms were associated with poorer quality of life.<br><br>CONCLUSIONS: These findings highlight poorer cognitive performance and higher cognitive and psychological symptoms in long COVID, suggesting the importance of comprehensive assessments and integrated rehabilitation strategies.},
}
@article {pmid40548319,
year = {2025},
author = {Guillen-Burgos, HF and Gálvez-Flórez, JF and Moreno-López, S and Wong, S and Kwan, ATH and Ramirez-Posada, M and Anaya, JM and McIntyre, RS},
title = {Major Depressive Disorder in Long COVID and Exposure to Pro-Inflammatory Cytokines During Infection by SARS-CoV-2.},
journal = {Psychiatric research and clinical practice},
volume = {7},
number = {2},
pages = {139-149},
pmid = {40548319},
issn = {2575-5609},
abstract = {OBJECTIVE: Major Depressive Disorder (MDD) is common in long COVID syndrome; however, the neurobiological mechanisms are unclear. An immune activation response has been associated with COVID-19 severity as well as in MDD. We hypothesize that high levels of pro-inflammatory cytokines during SARS-CoV-2 infection may be associated with new-onset MDD and severe outcomes such as treatment-resistant depression (TRD) and risk of suicide ideation and behavior (SI/SB).<br><br>METHODS: A case-control nested to a cohort study was carried out on a total of 678 COVID-19 survivors (MDD&#xa0;=&#xa0;184 vs. non-MDD&#xa0;=&#xa0;494). A pro-inflammatory panel of serum levels of cytokines (IL-1&#x3b2;, IL-4, IL-6, IL-8, IL-13, IL-17&#x3b1;, TNF-&#x3b1;) was evaluated during COVID-19 hospitalization and severe outcomes such as TRD and SI/SB were assessed in individuals with new onset of MDD after hospital discharge compared to non-MDD COVID-19 survivors.<br><br>RESULTS: High levels of pro-inflammatory cytokines during SARS-CoV-2 infection were identified in MDD participants compared to non-MDD subgroups during long COVID. These differences were sustained also for TRD and SI/SB severity outcomes. There is a mild association of high levels of pro-inflammatory cytokines and MDD, TRD, and SI/SB.<br><br>CONCLUSION: High levels of pro-inflammatory cytokines during severe or critical COVID-19 exposure may explain long COVID associated MDD and thus severe outcomes such as TRD and SI/SB.<br><br>Identifying elevated pro-inflammatory cytokines during COVID-19 as a risk factor for MDD and severe outcomes underscores the need for early screening and targeted treatments in long COVID. Monitoring cytokine levels may help clinicians predict and manage TRD and SI/SB in this population, improving long-term psychiatric outcomes.},
}
@article {pmid40546581,
year = {2025},
author = {Koster, M and Moore, LD and Inabnit, LS},
title = {Pulmonary Symptoms After Mild COVID-19: A Retrospective Observational Study.},
journal = {Cureus},
volume = {17},
number = {5},
pages = {e84499},
pmid = {40546581},
issn = {2168-8184},
abstract = {Background Patients have reported persisting or emerging symptoms weeks or months after the acute phase of a COVID-19 infection, even when the initial infection was mild or asymptomatic. Since data are limited on patients with a history of a mild acute phase, the pulmonary sequelae have been challenging to treat. The purpose of this study was to review diagnostic testing sessions from patients referred to the pulmonary function lab for a diagnosis or symptoms of long COVID following a mild acute phase. The collection and presentation of this data aim to provide insight into the possible cause of persistent pulmonary symptoms in this specific patient population. Methodology A retrospective review of patients at a single center who received pulmonary function test (PFT) and 6-minute walk test (6MWT) for long COVID symptoms following a mild acute phase of COVID-19 was conducted. Adult subjects were identified through electronic medical records if they received services between March 1, 2020, and September 2, 2023. The records of 19 patients were included in this review. Data analysis A Pearson correlation coefficient was used to analyze the relationship between dyspnea, pulmonary function impairment severity, and fatigue. The relationship between dyspnea and 6-minute walk test distance (6MWTD) was analyzed using the phi correlation coefficient. Results Weak correlations were identified between the reported symptoms of dyspnea and the severity of airway impairment, gas exchange, and 6MWTD. There was a strong positive correlation between dyspnea and fatigue. The sample size limits the analysis, but the data substantiate the need for additional research. Conclusion The severity of lung function impairments did not appear to correlate with the severity of dyspnea in patients following a mild acute phase of COVID-19. Therefore, pulmonary function impairments did not appear to be the primary cause of dyspnea. However, the symptoms of dyspnea and fatigue may contribute to each other.},
}
@article {pmid40545681,
year = {2025},
author = {Tsuchiya, H},
title = {Could Long COVID Oral Symptoms and COVID-19 Vaccination Oral Side Effects Be Induced by the Spike Protein?.},
journal = {Oral diseases},
volume = {},
number = {},
pages = {},
doi = {10.1111/odi.70005},
pmid = {40545681},
issn = {1601-0825},
support = {//Japan Society for the Promotion of Science/ ; },
}
@article {pmid40545236,
year = {2025},
author = {Wee, LE and Lim, JT and Tay, AT and Chiew, CJ and Young, BE and Vasoo, S and Lou, HX and Lye, DC and Tan, KB},
title = {Remdesivir and risk of long-term multi-systemic sequelae following COVID-19 hospitalization.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {31},
number = {10},
pages = {1704-1712},
doi = {10.1016/j.cmi.2025.06.016},
pmid = {40545236},
issn = {1469-0691},
mesh = {Humans ; Female ; Male ; *Antiviral Agents/therapeutic use/administration &amp; dosage ; Middle Aged ; Hospitalization/statistics &amp; numerical data ; Retrospective Studies ; *COVID-19 Drug Treatment ; Aged ; *COVID-19/complications/epidemiology ; *Adenosine Monophosphate/analogs &amp; derivatives/therapeutic use ; *Alanine/analogs &amp; derivatives/therapeutic use ; Adult ; SARS-CoV-2 ; Singapore/epidemiology ; Cardiovascular Diseases/epidemiology ; },
abstract = {OBJECTIVES: Significant heterogeneity has been reported in cohort studies evaluating the impact of antiviral treatment on long-term sequelae following COVID-19 hospitalization. We evaluated the impact of i.v. remdesivir on the risk of subsequent long-term cardiovascular/neurological/respiratory/autoimmune diagnoses and persistent symptoms.<br><br>METHODS: National COVID-19 registries and health care claims databases were utilized to construct a retrospective population-based cohort enrolling all adult Singaporeans hospitalized for COVID-19 (September 1, 2021-July 31, 2023) who fulfilled criteria for intravenous remdesivir. The cohort was divided into remdesivir-treated and untreated groups, with between group differences in baseline sociodemographic and clinical characteristics adjusted using overlap weighting. Risks of long-term new-incident (31-300 days) diagnoses/symptoms across cardiovascular/neurological/respiratory/autoimmune systems were compared across untreated/treated groups via competing-risks regression.<br><br>RESULTS: A total of 30 175 COVID-19 hospitalizations were included in the cohort for evaluating risk of long-term sequelae; 37.6% (11 353/30 175) received remdesivir. A total of 88.9% of the cohort were fully vaccinated, and 60.5% had received a booster dose; 77.4% were infected during Omicron. The risk of long-term new-onset diagnoses across cardiovascular, neurological, respiratory, and autoimmune systems (any long-term diagnosis, adjusted hazards ratio = 1.08 [95% CI, 0.97-1.20]) up to 300 days post-COVID-19-hospitalization was not significantly different in the remdesivir-treated group versus untreated individuals across age and vaccination subgroups. Similarly, no significant difference in the incidence of long-term symptom persistence at 300 days post-COVID-19 hospitalization was observed in the remdesivir-treated group versus untreated individuals.<br><br>DISCUSSION: Receipt of remdesivir did not significantly reduce risk of long-term multisystemic sequelae or long-term symptoms in a boosted cohort of adult Singaporeans hospitalized with COVID-19.},
}
@article {pmid40544471,
year = {2025},
author = {Akase, IE and Awodumila, SO and Nwanmah, CE and Ojo, OO and Agabi, OP and Ede, O and Nwaokorie, FO and Anyanwu, RA and Ghajiga, PS and Kalejaiye, O and Perez-Giraldo, GS and Orban, ZS and Jimenez, M and Koralnik, IJ and Okubadejo, NU},
title = {A Social Media Survey on the Prevalence of Post-COVID Neurologic Complications Among Nigerians.},
journal = {West African journal of medicine},
volume = {42},
number = {1},
pages = {29-35},
pmid = {40544471},
issn = {0189-160X},
mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; *Nervous System Diseases/epidemiology/etiology/virology ; Nigeria/epidemiology ; Prevalence ; *Social Media ; Surveys and Questionnaires ; West African People ; },
abstract = {BACKGROUND AND OBJECTIVE: Cultural barriers and perceptual factors that are peculiar among Africans are known to limit the number of people seeking medical care for post-COVID conditions. The aim of this social media survey was to ascertain the burden of post-COVID neurologic complications in Nigeria in individuals with confirmed COVID-19.<br><br>METHODS: We performed a cross-sectional web-based survey of persons with PCR-confirmed or suspected SARS-CoV-2 infection in Nigeria with incident infection between March 2020 and April 2022. Our survey utilized Kobo Toolbox&#xae; and was disseminated via several online platforms (including WhatsApp &#xae;, Facebook&#xae;, and Twitter (X)&#xae;). Participant demographics, COVID-19 symptom profile, SARS-CoV-2 test results, and the occurrence of persistent neurological symptoms were documented.<br><br>RESULTS: We analyzed the data of 963 participants with confirmed or suspected COVID-19 infection. The mean age was 36.9 &#xb1; 9.9 years, and 555/963 (57.6%) were female. Only 174/963 individuals (18.1%) had SARS-CoV-2 PCR confirmation at any point during the pandemic, of which 133 (76.4%) had accompanying symptoms consistent with the case definition. A total of 47/174 (27.0%) of the PCR-positive participants reported post-acute COVID symptoms, and 46/174 (26.4%) had post-COVID neurologic complaints. The most commonly reported symptoms were fatigue (25; 14.4%), generalized body weakness (22; 12.6%), and difficulty remembering things (15; 8.6%). Slightly over half of those with post-COVID symptoms (25/47; 53.2%) sought care, with 21/25 (84%) presenting to a medical facility. Others presented either to a community pharmacy (1/25) or a patent medicine store (3/25) for care.<br><br>CONCLUSION: Despite low testing rates in Nigeria, the prevalence of post-COVID neurologic complications is approximately 1 in 4 individuals. Further studies on the prognosis and management of post-COVID neurologic sequelae in Nigeria are warranted.},
}
@article {pmid40544138,
year = {2025},
author = {D'hoore, L and Germonpré, P and Rinia, B and Caeyers, L and Stevens, N and Balestra, C},
title = {Effect of normobaric and hyperbaric hyperoxia treatment on symptoms and cognitive capacities in Long COVID patients: a randomised placebo-controlled, prospective, double-blind trial.},
journal = {Diving and hyperbaric medicine},
volume = {55},
number = {2},
pages = {104-113},
pmid = {40544138},
issn = {1833-3516},
mesh = {Humans ; *Hyperbaric Oxygenation/methods ; Male ; Female ; *COVID-19/therapy/complications/psychology ; Middle Aged ; Prospective Studies ; Double-Blind Method ; Quality of Life ; Adult ; *Cognition ; Aged ; Treatment Outcome ; Walk Test ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long COVID syndrome is a major health issue. Multiple treatments have been proposed but efficacy is inadequately investigated. Hyperbaric oxygen therapy (HBOT) has been promoted based on a small number of publications. As there is potential for a placebo effect and the financial cost of HBOT is high, we sought to investigate the effects of HBOT in Long COVID in a randomised trial.<br><br>METHODS: We randomised 101 patients into four treatment groups, receiving 10 sessions of oxygen 'treatment' inside a pressure chamber, according to one of four modalities: A - 100% oxygen at 253 kPa (2.5 atmospheres absolute); B - 40% oxygen at 253 kPa; C - 100% oxygen at 101.3 kPa (1 atmosphere absolute); D - 21% oxygen at 101.3 kPa. Groups B and C thus received a similar effective oxygen dose of 101.3 kPa. Quality of life symptom scores (Visual Analogue Scale; EQ-5D-5L, C19-YRSm), a 6-minute walking test and five neurocognitive tests were administered before and after the treatment series. At three months post-treatment, a telephone questionnaire probed for lasting effects.<br><br>RESULTS: All groups were comparable with regards to demographics, Long COVID symptoms and severity. After treatment, there were no significant differences in subjective symptoms, functional scores, and cognitive performance between any groups. The response to treatment was highly variable, with some patients in even the 'placebo' group D reporting a significant improvement in their well-being. This was not reflected in any objective outcome scores. No subgroups of patients responded better to any of the treatments.<br><br>CONCLUSIONS: There was no significant effect from different doses of oxygen in a hyperbaric chamber. It is possible that the very modest improvements reported in other studies were due to a placebo effect. Claims that HBOT has a significant effect on Long COVID need further investigation before indiscriminately prescribing or promoting HBOT.},
}
@article {pmid40544080,
year = {2025},
author = {Mateu-Campos, ML and Altaba-Tena, S and Boscá-Martínez, B and Camáñez-Fortanet, J and Viana-Marco, C and González-Núñez, AB and Villanova-Landete, AR and Sánchez-Morán, F and Navarro-Alcaraz, R},
title = {Clinical impact of COVID-19 respiratory infection 15 months after intensive care unit discharge.},
journal = {Medicina intensiva},
volume = {},
number = {},
pages = {502230},
doi = {10.1016/j.medine.2025.502230},
pmid = {40544080},
issn = {2173-5727},
abstract = {OBJECTIVES: To determine the prevalence of persistent COVID-19 symptoms in SARS-CoV-2 patients 15 months after ICU discharge,their impact on physical, psychological, and neurocognitive domains, and the burden on primary caregivers.<br><br>DESIGN: Descriptive, ambispective observational study.<br><br>SETTING: Intensive Care Unit from a tertiary-level hospital.<br><br>PATIENTS: SARS-CoV-2 patients discharged from ICU.<br><br>MAIN VARIABLES OF INTEREST: demographics and hospitalization data. Questionnaires assesing persistent COVID symptoms, functional tests (6-Minute Walk Test), anxiety (Beck Anxiety Inventory), PTSD and Zarit Caregiver Burden scales. Statistical analysis was performed using Stata for Mac, version 14.2.<br><br>RESULTS: 85 patients were evaluated, with a median age of 60.3 years (IQR 54.0-68.9), 70.6% males. A high percentage of patients reported musculoskeletal disorders such as arthralgia (44.7%) and myalgia (38.2%), cognitive impairments (52.9%), sleep disturbances (34.1%), asthenia (44.5%) and anxiety (34.5%). The overall BAI score was 2 (0-9), with paraesthesia being the most common symptom. Additionally, 29.4% of patients reported "fear of the worst", 35% had unpleasant or recurrent memories of their ICU stay, and 16.4% were unable to relax (moderate/severe degree). Interviews with primary caregivers revealed that 22.2% reported caregiving as a significant burden.<br><br>CONCLUSIONS: persistent COVID affects three primary functional domains: physical, cognitive and psychological, as well as on primary caregivers concerns and burdens.},
}
@article {pmid40543387,
year = {2025},
author = {Beuren, T and Ferrari, F and Franzoni, LT and Goulart, CDL and Val, F and Cipriano, G and Stein, R},
title = {Exploring the interplay between host genetics and acute and long COVID: A narrative review.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100708},
pmid = {40543387},
issn = {1980-5322},
mesh = {Humans ; *COVID-19/genetics/immunology ; *Genetic Predisposition to Disease/genetics ; SARS-CoV-2 ; },
abstract = {Over the past four years, pivotal discoveries have deepened the understanding of the relationship between genetic factors and SARS-CoV-2 infection. Numerous genes associated with severe COVID-19 suggest a potential genetic predisposition, which may help explain why some individuals develop more serious illnesses. Emerging evidence highlights the role of genes involved in pulmonary immunity, such as Forkhead box Protein P4 (FOXP4), whose increased expression in lung tissue has been linked to more severe disease. Other genes - Transmembrane Protease Serine-2 (TMPRSS2), Leucine Zipper Transcription Factor Like-1 (LZTFL1), Solute Carrier family 6 member 20 (SLC6A20), Tyrosine Kinase-2 (TYK2), Angiotensin-Converting Enzyme (ACE), and FYVE and Coiled-Coil Domain-Containing-1 (FYCO1) - have also been implicated in COVID-19 severity. In contrast, certain genetic variants - such as the T-allele of rs12329760 in the TMPRSS2 gene and rs35705950-T in the Mucin-5B (MUC5B) gene - may confer protection against severe disease. Overall, the evidence suggests that genetic factors can influence both susceptibility to and protection from severe COVID-19, although these associations are likely shaped by complex interactions with environmental, behavioral, and other biological factors. This review summarizes current knowledge on genetic determinants linked to COVID-19 outcomes.},
}
@article {pmid40542858,
year = {2025},
author = {van Leer, B and Londema, M and Kasalak, &#xd6; and van Snick, JH and Duiverman, ML and Kuijvenhoven, JC and de Kruif, MD and Oprea-Lager, DE and Pabst, K and Hellemons, ME and Boersma, HH and Prokop, M and Nijsten, MW and Glaudemans, AWJM and Pillay, J and Slart, RHJA and , },
title = {[[68]Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {53},
number = {1},
pages = {565-573},
pmid = {40542858},
issn = {1619-7089},
support = {50-56300-98-2104/ZONMW_/ZonMw/Netherlands ; 50-56300-98-2104/ZONMW_/ZonMw/Netherlands ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; *COVID-19/diagnostic imaging/metabolism/complications ; *Lung/diagnostic imaging/metabolism ; Gallium Radioisotopes ; Aged ; *Patient Discharge ; *Membrane Proteins/metabolism ; *Serine Endopeptidases/metabolism ; Prospective Studies ; Endopeptidases ; Quinolines ; Fibroblast Activation Protein Alpha ; },
abstract = {PURPOSE: Post-acute sequelae of COVID-19 (PASC) has emerged as a major healthcare problem. A comprehensive mechanism of disease remains to be elucidated. In this study we aimed to explore pulmonary and muscle fibroblast activation protein (FAP) activity in former critical COVID-19 patients with persistent dyspnea, using [[68]Ga]FAPI-46 PET/CT.<br><br>METHODS: In this single center prospective observational study we included former critical COVID-19 patients reporting complaints of dyspnea&#x2009;>&#x2009;3&#xa0;months after hospital discharge. A [[68]Ga]FAPI PET/CT scan was performed including a high-resolution CT scan, lung function test, EQ-5D questionnaire, 6 min walking test and inflammatory markers. Age and sex-matched subjects, without pulmonary pathology, served as controls. The [[68]Ga]FAPI uptake was corrected for lean body mass and the target-to-background ratio (TBR) was calculated.<br><br>RESULTS: Eighteen PASC patients and 15 controls (median age 59 and 63 years and BMI of 34.6 and 25.2 kg/m[2]) were included. The interval between hospital discharge and study visit was 30 months. Increased pulmonary FAP expression was observed in PASC, (TBR 0.79&#x2009;&#xb1;&#x2009;0.23) compared to controls (TBR 0.40&#x2009;&#xb1;&#x2009;0.13, P&#x2009;<&#x2009;0.001). Increased FAP expression was also observed in the paravertebral muscles (PASC: TBR 1.17 and controls TBR 1.00, P&#x2009;=&#x2009;0.03). Forced expiratory volume and forced vital capacity showed moderate negative correlation with the pulmonary TBR, while the percentage of ground glass opacities showed a moderate positive correlation.<br><br>CONCLUSION: [[68]Ga]FAPI PET/CT demonstrated elevated FAP expression in PASC. These findings provide insight into possible pathophysiological mechanisms of PASC and a potential new diagnostic modality.},
}
@article {pmid40542141,
year = {2025},
author = {Harsányi, L and Kincses, Z and Veselinović, M and Zehetner, J and Altorjay, &#xc1;},
title = {Food passageway-related sequelae in the RefluxStop prospective multicenter trial: patient-centric outcomes of dysphagia, odynophagia, gas-bloating, and inability to belch and/or vomit at 5 years.},
journal = {Surgical endoscopy},
volume = {39},
number = {7},
pages = {4615-4627},
pmid = {40542141},
issn = {1432-2218},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Deglutition Disorders/etiology/epidemiology ; *Eructation/etiology/epidemiology ; Flatulence/etiology ; Follow-Up Studies ; *Fundoplication/methods/adverse effects ; *Gastroesophageal Reflux/surgery/complications ; *Postoperative Complications/etiology/epidemiology ; Prospective Studies ; Quality of Life ; Treatment Outcome ; },
abstract = {INTRODUCTION: Standard surgical management of GERD may result in troublesome postoperative food passageway-related sequelae (i.e., dysphagia, odynophagia, gas-bloat syndrome, inability to belch/vomit), significantly impacting quality of life. Five-year results after the RefluxStop procedure are presented, involving reconstruction of the anti-reflux barrier without encircling the food passageway, reducing such related sequelae.<br><br>METHODS: RefluxStop surgery was evaluated in a prospective, single-arm, multicenter study with 50 GERD subjects. This report focuses on food passageway-related outcomes. Other basic outcomes (e.g., 24-h pH, PPI usage) are presented in a separate report with brief clinical correlation herein.<br><br>RESULTS: Forty-four subjects completed 5-year follow-up; three participants were missing due to COVID-19 (i.e., two deaths and one bedbound with long-COVID) and three terminated early. Data from 3- and 4-year follow-up were carried forward in COVID-affected cases. Food passageway-related adverse events (AEs) between 2&#xa0;weeks of surgical recovery and 5-year follow-up included: one case (2.1%) of dysphagia (and another case, mild dysphagia for 2&#xa0;weeks postoperatively, viewed as normal recovery); one case (2.1%) of odynophagia; zero (0%) cases of inability to belch/vomit; and gas-bloating none/improved in 42 cases with only two worsening. These outcomes were well-aligned with improvement in total GERD-HRQL score (i.e., median 29.5 at baseline to 3.0 at 5&#xa0;years), PPI usage (2.1%), and 24-h pH monitoring (i.e., mean 1.57% acid exposure time at 5&#xa0;years).<br><br>CONCLUSION: RefluxStop surgery resulted in a favorable profile of food passageway-related outcomes throughout the 5-year study: no AE dysphagia in 97.9% of subjects; no AE odynophagia in 97.9%; whereof at 5&#xa0;years: gas-bloating none/improved in 95.7%, and no inability to belch/vomit in 100%. For clinical correlation, 97.9% of subjects did not take PPIs at 5&#xa0;years. These outcomes add resolution to the overall treatment effect of RefluxStop and may show potential preference in GERD patients who prioritize minimization of postoperative sequelae.},
}
@article {pmid40540816,
year = {2025},
author = {Filho, ADC and Fakoury, MK and Schmidt, GJ and Taboada Gjorup, AL and Marques, AC and Tolentino Junior, JC and Schmidt, JJ and Maia, A and van Duinkerken, E and Lewandrowski, KU and Blum, K and Schmidt, SL},
title = {Long-COVID-19 and Cognition: Persistent attention deficits after hospital discharge.},
journal = {Journal of psychiatric research},
volume = {189},
number = {},
pages = {277-279},
doi = {10.1016/j.jpsychires.2025.06.009},
pmid = {40540816},
issn = {1879-1379},
}
@article {pmid40540397,
year = {2025},
author = {Schneiderova, P and Mizera, J and Gharibian, A and Manukyan, G and Raska, M and Gajdos, P and Kosztyu, P and Genzor, S and Kudelka, M and Sova, M and Savara, J and Borikova, A and Shrestha, B and Mikulkova, Z and Stepanek, L and Kufa, J and Jakubec, P and Kriegova, E},
title = {The SARS-CoV-2 trigger highlights host interleukin 1 genetics in Epstein-Barr virus reactivation.},
journal = {Cell reports},
volume = {44},
number = {7},
pages = {115859},
doi = {10.1016/j.celrep.2025.115859},
pmid = {40540397},
issn = {2211-1247},
mesh = {Humans ; *Herpesvirus 4, Human/physiology/immunology ; *Virus Activation/genetics ; *COVID-19/virology/immunology/genetics ; *SARS-CoV-2/physiology ; *Epstein-Barr Virus Infections/genetics/virology/immunology ; Male ; Female ; Middle Aged ; Interleukin 1 Receptor Antagonist Protein/genetics ; *Interleukin-1/genetics ; Adult ; Interleukin-10/genetics ; Interleukin-1beta/genetics ; Aged ; Immunoglobulin A ; Interleukin-1alpha/genetics ; Antibodies, Viral/blood ; Antigens, Viral/immunology ; },
abstract = {Studies in large cohorts exposed to the same triggers associated with Epstein-Barr virus (EBV) reactivation and the follow-up of post-acute outcomes may uncover the pathomechanisms of autoimmune conditions and EBV-related cancer. We investigated a large cohort of individuals infected with SARS-CoV-2 infection reporting long COVID (LC) symptoms for positive serological markers of recent EBV reactivation (viral capsid antigen [VCA] immunoglobulin [Ig]M, VCA IgA, and early antigen D IgG), host interleukin (IL)1 and IL10 genetics, and immune response. Recent EBV reactivation occurs more frequently in individuals with a genetic risk of EBV reactivation in the IL1RN, IL1A, and IL1B genes associated with an elevated ratio of IL-1 receptor antagonist (IL-1Ra)/IL-1β and a higher latent EBV load in blood. High levels of anti-VCA IgA serve as a strong marker of recent EBV reactivation, which is associated with objective long-term pulmonary dysfunction in LC. Our data highlight the association between host IL1 genetics and EBV reactivation.},
}
@article {pmid40540167,
year = {2025},
author = {Lang, SM and Schiffl, H},
title = {Long-term renal consequences of COVID-19. Emerging evidence and unanswered questions.},
journal = {International urology and nephrology},
volume = {57},
number = {12},
pages = {4169-4176},
pmid = {40540167},
issn = {1573-2584},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Renal Insufficiency, Chronic/epidemiology/etiology ; *Acute Kidney Injury/epidemiology ; SARS-CoV-2 ; },
abstract = {PURPOSE: COVID-19 infection is associated with a high burden of acute or acute on chronic kidney injury (AKI), particularly in critically ill patients. Given the large numbers of COVID-19 survivors, characterization of long-term adverse kidney effects of COVID-19 have important implications for post-COVID-19 care.<br><br>METHODS: This narrative review provides a summary of epidemiologic evidence for post-COVID kidney disorders.<br><br>RESULTS: Precise post-COVID renal data are scarce. The true burden of long-COVID chronic kidney disease (CKD) remains unknown owing to under-recognition, under-diagnosis, clinical heterogeneity of patients, incomplete follow-up, and temporal trends in critical COVID-19 disease across waves of the pandemic. Collectively, the few well-designed studies assessing the impact of long-COVID on kidney health found that the overwhelming majority of patients with normal renal function at admission and without AKI during acute COVID-19 disease preserved kidney function. Post-infection kidney function trajectories of patients who experience a loss of renal function vary. Kidney function may decline gradually even in non-hospitalized patients, hospitalized patients may experience a rapid loss of kidney function 6-12&#xa0;months after COVID-19 diagnosis or hospital discharge resulting from AKI during the acute phase of the disease. End-stage renal disease may occur after non-recovery from AKI and rapid progression of pre-existing CKD. Multiple mechanisms may trigger post-COVID CKD including maladaptive repair after AKI, or progression of renal lesions of systemic co-morbidities, persistence of the virus and dysregulation of inflammatory cytokines.<br><br>CONCLUSIONS: The COVID-19 pandemic has significantly impacted and may continue to have an impact on kidney health. Patients at risk have a higher propensity to develop critical COVID-19 disease. Post-COVID-19 care must pay close attention to renal function in patients discharged from hospital.},
}
@article {pmid40539617,
year = {2025},
author = {Souza, LMDN and Prigatano, GP and de Oliveira, SB and Braga, LW},
title = {Cognitive and Affective Performance of Brazilian Long COVID Patients: An In-Depth Analysis Before and After Psychoeducational Rehabilitation.},
journal = {NeuroRehabilitation},
volume = {56},
number = {4},
pages = {451-462},
doi = {10.1177/10538135251327122},
pmid = {40539617},
issn = {1878-6448},
mesh = {Humans ; Male ; Female ; *COVID-19/psychology/rehabilitation/complications ; Middle Aged ; Brazil ; Adult ; Aged ; Neuropsychological Tests ; *Cognitive Dysfunction/rehabilitation/etiology ; Patient Education as Topic ; },
abstract = {BackgroundLong COVID patients report various cognitive and affective symptoms that are poorly understood.ObjectiveThis study analyzed cognitive and affective performance in 208 Long COVID patients pre and post psychoeducational rehabilitation using a standardized screening test of higher cerebral functions. Identifying persistent difficulties may help guide future rehabilitation efforts.MethodsThe sample was comprised by a subset of 208 who completed psychoeducational rehabilitation from 614 Long COVID patients seeking rehabilitation. Performance on specific items was analyzed and compared to a reference sample of 114 educationally matched normal functioning adults.ResultsDetailed item analyses in 208 patients revealed persistent difficulties in the efficiency of learning and memory, affective expression, and the ability to accurately predict verbal memory performance compared to a reference sample. Long COVID patients showed variable performance deficits on attention, visual-spatial problem solving and memory measures. Language and related functions were consistently at a level commensurate with normally functioning individuals.ConclusionsPersistent cognitive and affective impairments were identified in Long COVID patients post-rehabilitation. Future programs should aim on to improve the efficiency of learning and memory, enhance the range of affective expression, and improve self-awareness of functional capacities. Rehabilitation should consider the multifactorial causes of these neuropsychological symptoms.},
}
@article {pmid40537277,
year = {2025},
author = {},
title = {Long COVID: equity in research.},
journal = {Archives of disease in childhood},
volume = {110},
number = {7},
pages = {527},
doi = {10.1136/archdischild-2025-329167},
pmid = {40537277},
issn = {1468-2044},
}
@article {pmid40537100,
year = {2025},
author = {Maas, MB and Reid, KJ and Jimenez, M and Lopez, M and Miller, J and Carnethon, MR and Zee, PC and Knutson, KL and Koralnik, IJ},
title = {Multidimensional Characterization of Long COVID Fatigue.},
journal = {Behavioral sleep medicine},
volume = {23},
number = {5},
pages = {675-684},
pmid = {40537100},
issn = {1540-2010},
support = {P01 AG011412/AG/NIA NIH HHS/United States ; R01 AG059291/AG/NIA NIH HHS/United States ; R01 HL140580/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Fatigue/physiopathology/etiology/psychology ; Middle Aged ; Male ; *COVID-19/complications/psychology ; Actigraphy ; *Circadian Rhythm/physiology ; Adult ; Depression/physiopathology/psychology/etiology ; Polysomnography ; Sleep/physiology ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/physiopathology/etiology ; Severity of Illness Index ; Cognition/physiology ; Self Report ; },
abstract = {OBJECTIVES: We performed a multidimensional analysis of mood, cognition, sleep and circadian rhythms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC) with the objective of characterizing the phenotype of PASC fatigue.<br><br>METHODS: We recruited adult patients from a Neuro-COVID-19 Clinic with persistence of disabling symptoms beyond 6&#x2009;weeks from acute infection. Self-reported symptoms were assessed with Patient-Reported Outcomes Measurement Information System instruments. We evaluated cognitive performance using NIH Toolbox measures and assessed sleep and rest-activity rhythms by 7&#x2009;days of wrist actigraphy. We performed level 2 polysomnography in a subset of 20 participants.<br><br>RESULTS: We studied 58 participants: 83% White, 59% female and 91% not hospitalized for COVID-19. Fatigue severity was significantly correlated with worse self-reported cognitive abilities but not with objectively measured cognitive performance and with greater depression symptoms, several rest-activity rhythm and light exposure disruption measures, and greater actigraphy measured sleep time and time in bed. A multivariable model found significant, independent associations between fatigue severity and subjective cognitive abilities, depression symptoms, and rest-activity rhythm disruption.<br><br>CONCLUSIONS: Long total sleep times, disruption of light exposure and circadian rest-activity patterns, depression and subjective cognitive impairment are associated with PASC fatigue. Behaviorally influenced sleep and circadian abnormalities may exacerbate fatigue and be targets for therapeutic interventions.},
}
@article {pmid40536011,
year = {2025},
author = {Moen, JK and Baker, CA and Iwasaki, A},
title = {Neuroimmune pathophysiology of long COVID.},
journal = {Psychiatry and clinical neurosciences},
volume = {79},
number = {9},
pages = {514-530},
pmid = {40536011},
issn = {1440-1819},
support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; R01AI157488//National Institute of Allergy and Infectious Diseases/ ; N/A/HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Humans ; *COVID-19/immunology/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Neuroimmunomodulation/physiology ; *Nervous System Diseases/immunology/physiopathology/etiology ; SARS-CoV-2 ; Animals ; *Peripheral Nervous System Diseases/immunology/physiopathology/etiology ; Fatigue/physiopathology/immunology ; },
abstract = {Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.},
}
@article {pmid40535019,
year = {2025},
author = {Palchevska, O and Dominguez, F},
title = {Syncytium: the viral escape room secret to persistent infection of SARS-CoV-2.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1561274},
pmid = {40535019},
issn = {1664-302X},
}
@article {pmid40534826,
year = {2025},
author = {Souissi, A and Prieto-González, P and Ben Saad, H},
title = {Widespread pain syndrome in long COVID-19: melatonin as an adjuvant treatment.},
journal = {Frontiers in pain research (Lausanne, Switzerland)},
volume = {6},
number = {},
pages = {1609095},
pmid = {40534826},
issn = {2673-561X},
abstract = {Long coronavirus disease 2019 (LC19) represents a complex global health challenge. Survivors frequently report persistent problems like widespread pain syndrome (WPS), cognitive dysfunction, cardiovascular complications, and sleep disturbances. These health problems, which are worsened by oxidative stress and inflammaging, open the prospect of treatment strategies targeting these mechanisms. Melatonin is a potential option for treating LC19 problems because of its anti-inflammatory, antioxidant, and pain-modulating properties. Melatonin targets shared pathological pathways, offering a promising approach to reducing inflammation, oxidative stress, and neuroendocrine dysfunction. The present mini-review explores the therapeutic potential of melatonin in the treatment of LC19, focusing on its effects on WPS and inflammation.},
}
@article {pmid40534631,
year = {2025},
author = {Shah, SA and Phan, Q and Radel, JA},
title = {Role of enhanced external counterpulsation in long COVID.},
journal = {Open medicine (Warsaw, Poland)},
volume = {20},
number = {1},
pages = {20251216},
pmid = {40534631},
issn = {2391-5463},
}
@article {pmid40532111,
year = {2026},
author = {Risbano, MG},
title = {From fatigue to physiology: Submaximal 2-day cardiopulmonary exercise test and emerging standards in long COVID.},
journal = {Experimental physiology},
volume = {111},
number = {2},
pages = {344-345},
pmid = {40532111},
issn = {1469-445X},
support = {R01 HL176493/HL/NHLBI NIH HHS/United States ; 2025//Shadyside Hospital Foundation/ ; 1R01HL176493-01//HHS | NIH | NHLBI | Division of Intramural Research (DIR)/ ; },
}
@article {pmid40531392,
year = {2025},
author = {da Silva, MD and da Silva, TS and Mendes, CG and Valbão, MCM and Badu-Tawiah, AK and Laurindo, LF and Barbalho, SM and Direito, R and Miglino, MA},
title = {Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification.},
journal = {Molecular diagnosis &amp; therapy},
volume = {29},
number = {5},
pages = {617-636},
pmid = {40531392},
issn = {1179-2000},
support = {200177/2022-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
mesh = {Humans ; *COVID-19/metabolism/virology/complications/physiopathology ; *Biomarkers/metabolism/analysis ; Metabolomics/methods ; *SARS-CoV-2 ; Proteomics/methods ; Lipidomics ; Post-Acute COVID-19 Syndrome ; Risk Factors ; },
abstract = {Long coronavirus disease (COVID) is a multisystem condition that affects a significant proportion of individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with persistent symptoms ranging from fatigue and cognitive dysfunction to cardiovascular disorders. It is estimated that 30-60% of infected individuals experience symptoms lasting more than 12 weeks. Despite advances in understanding acute infection, the pathophysiological mechanisms underlying long COVID remain unclear. Current hypotheses suggest that viral persistence, immune dysfunction, and metabolic alterations play central roles. Omics approaches, including metabolomics, proteomics, and lipidomics, have played a crucial role in investigating molecular changes, identifying biomarkers, and refining therapeutic strategies. This review discusses recent advances in understanding long COVID, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.},
}
@article {pmid40529374,
year = {2025},
author = {Trautmann, A},
title = {Core features and inherent diversity of post-acute infection syndromes.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1509131},
pmid = {40529374},
issn = {1664-3224},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Animals ; Fatigue/etiology ; *Infections/immunology/complications ; Critical Illness ; },
abstract = {Post-acute infection syndromes (PAIS), i.e., long-lasting pathologies subsequent to infections that do not properly resolve, have both a common core and a broad diversity of manifestations. PAIS include a group of core symptoms (pathological fatigue, cognitive problems, sleep disorders and pain) accompanied by a large set of diverse symptoms. Core and diverse additional symptoms, which can persist for years, exhibiting periods of relapses and remissions, usually start suddenly after an apparently common infection. PAIS display highly variable clinical features depending on the nature of the initial pathogen, and to an even larger extent, on the diversity of preexisting individual terrains in which PAIS are rooted. In a first part, I discuss biological issues related to the persistence of microbial antigens, dysregulated immune responses, reactivation of latent viruses, different potential self-sustained inflammatory loops, mitochondrial dysfunction, metabolic disorders in the tryptophan- kynurenin pathway (TKP) with impact on serotonin, and consequences of a dysfunctional bidirectional microbiota-gut-brain axis. The second part deals with the nervous system dependence of PAIS. I rely on the concept of interoception, the process by which the brain senses, integrates and interprets signals originating from within the body, and sends feebacks aimed at maintaining homeostasis. Interoception is central for understanding the origin of fatigue, dysautonomia, dysfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis, and its relation with stress, inflammation or depression. I propose that all individual predispositions leading to self-sustained vicious circles constitute building blocks that can self-assemble in many possible ways, to give rise to both core and diverse features of PAIS. A useful discrimination between different PAIS subtypes should be obtained with a composite profiling including biomarkers, questionnaires and functional tests so as to take into account PAIS multidimensionality.},
}
@article {pmid40529123,
year = {2025},
author = {Pasharawipas, T},
title = {Perspective: host factors variants and the underlying causes of long COVID.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1603317},
pmid = {40529123},
issn = {2296-858X},
abstract = {Long COVID, also known as post-COVID syndrome (PCS), is characterized by persistent and unexplained symptoms that can occur not only in individuals who experienced severe symptoms during the acute phase of SARS-CoV-2 infection but also in those who were asymptomatic or had only mild symptoms. These symptoms may persist for months, even in individuals who test negative via nasopharyngeal swab samples. This proposal aims to explain the cause of long COVID through the concept of host factor variants, including cellular variants and major histocompatibility complex (MHC) polymorphisms. A key aspect of this hypothesis is the role of antigen-presenting cells, such as macrophages and dendritic cells. It is proposed that blood or white blood cells could serve as suitable samples for diagnosing long COVID in affected individuals.},
}
@article {pmid40522927,
year = {2025},
author = {Özden, ME and Temizer, M},
title = {"Long COVID in patients with systemic lupus erythematosus: A case‒control study"-a methodological consideration.},
journal = {Lupus},
volume = {34},
number = {9},
pages = {982-983},
doi = {10.1177/09612033251352722},
pmid = {40522927},
issn = {1477-0962},
}
@article {pmid40520224,
year = {2025},
author = {Lovaglio, PG and Borgonovo, F and Manzo Margiotta, A and Mowafy, M and Colaneri, M and Bandera, A and Gori, A and Capetti, AF},
title = {Estimating long COVID-19 prevalence across definitions and forms of sample selection.},
journal = {Frontiers in epidemiology},
volume = {5},
number = {},
pages = {1597799},
pmid = {40520224},
issn = {2674-1199},
abstract = {INTRODUCTION: Long COVID (LC) is a multisystem condition with prolonged symptoms persisting beyond acute SARS-CoV-2 infection. However, prevalence estimates vary widely due to differences in case definitions and sampling methodologies. This study aims to determine the prevalence of LC across different definitions and correct for selection bias using advanced statistical modeling.<br><br>METHODS: We conducted a retrospective, observational study at Luigi Sacco Hospital (Milan, Italy), analyzing 3,344 COVID-19 patients from two pandemic waves (2020-2021). Participants included 1,537 outpatients from the ARCOVID clinic and 1,807 hospitalized patients. LC was defined based on WHO and NICE criteria, as well as two alternative definitions: symptoms persisting at 3 and 6 months post-infection. We used a bivariate censored Probit model to account for selection bias and estimate adjusted LC prevalence.<br><br>RESULTS: LC prevalence varied across definitions: 67.4% (WHO), 76.3% (NICE), 80.2% (3 months), and 79.6% (6 months). Adjusted prevalence estimates remained consistent across definitions. The most common symptoms were fatigue (58.6%), dyspnea (41.1%), and joint/muscle pain (39.2%). Risk factors included female sex (OR 2.165-2.379), metabolic disease (OR 1.587-1.629), and older age (40-50 years, OR 1.847). Protective factors included antiplatelets (OR 0.640-0.689), statins (OR 0.616), and hypoglycemics (OR 0.593-0.706). Vaccination, hydroxychloroquine, and antibiotics were associated with an increased risk of LC. Selection bias significantly influenced prevalence estimates, underscoring the need for robust statistical adjustments.<br><br>DISCUSSION: Our findings highlight the high prevalence of LC, particularly among specific subgroups, with strong selection effects influencing outpatient participation. Differences in prevalence estimates emphasize the impact of case definitions and study designs on LC research. The identification of risk and protective factors supports targeted interventions and patient management strategies.<br><br>CONCLUSION: This study provides one of the most comprehensive analyses of LC prevalence while accounting for selection bias. Our findings call for standardized LC definitions, improved epidemiological methodologies, and targeted prevention strategies. Future research should explore prospective cohorts to refine LC prevalence estimates and investigate long-term health outcomes.},
}
@article {pmid40519702,
year = {2025},
author = {Al Masoodi, WT and Radhi, SW and Abdalsada, HK and Al-Hakeim, HK},
title = {Role of Galanin system and insulin resistance parameters as predictive tools for diagnosis of Long-COVID patients.},
journal = {Biochemistry and biophysics reports},
volume = {43},
number = {},
pages = {102068},
pmid = {40519702},
issn = {2405-5808},
abstract = {BACKGROUND: COVID-19 patients may have long-lasting symptoms known as long-COVID (LC) without any underlying medical issues or obvious organ damage. Much research suggested that these issues are attributed to cytokine storm, lung and nerve injury, and glucose homeostasis disruption. Galanin (Gal), a neuropeptide in the peripheral and central nervous systems, has several physiological activities connected to illnesses. The current case-control research hypothesized the role of insulin resistance (IR) and the Gal system in LC pathophysiology.<br><br>METHODS: This research included 30 healthy controls and 60 LC patients. Insulin, Gal, and GalR1 were determined using the enzyme-linked immunosorbent assay (ELISA). The HOMA2 calculator determined &#x3b2;-cell function (HOMA%B), insulin sensitivity (HOMA%S), and insulin resistance (HOMA2IR) by analyzing fasting serum insulin and glucose levels.<br><br>RESULTS: LC patients showed higher Gal, GalR1, and Gal/GalR1 concentrations than controls, suggesting Gal system activation. LC patients likely have an IR state. The correlation study showed a negative link between Gal, GalR1, and SpO2. Gal level was positively correlated with insulin, insulin/glucose, and HOMA2IR and negatively correlated with HOMA%S. With an AUC-ROC of 0.939, artificial neural networks (ANN) predicted a sensitivity of 71.4&#xa0;% and a specificity of 87.5&#xa0;%. In LC, IR parameters and Gal system biomarkers were strongly correlated, suggesting they may contribute to disease.<br><br>CONCLUSION: Galanin system and IR parameters are altered in LC patients and can predict LC in suspicious subjects with 91.7&#xa0;% sensitivity and 100.0&#xa0;% specificity using the neural network model. The top five predictors were CRP, insulin/glucose, Gal, glucose, and GalR1. CRP had the greatest importance (100.0&#xa0;%), indicating the importance of inflammation, IR, and Gal system biomarkers in the pathophysiology of LC.},
}
@article {pmid40518292,
year = {2025},
author = {Vivaldi, G and Talaei, M and Blaikley, J and Jackson, C and Pfeffer, PE and Shaheen, SO and Martineau, AR},
title = {Bidirectional relationship between sleep problems and long COVID: a longitudinal analysis of data from the COVIDENCE UK study.},
journal = {BMJ open respiratory research},
volume = {12},
number = {1},
pages = {},
pmid = {40518292},
issn = {2052-4439},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/complications/epidemiology ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Risk Factors ; Sleep Quality ; *Sleep Wake Disorders/epidemiology ; United Kingdom/epidemiology ; },
abstract = {BACKGROUND: Studies into the bidirectional relationship between sleep and long COVID have been limited by retrospective pre-infection sleep data and infrequent post-infection follow-up. We therefore used prospectively collected monthly data to evaluate how pre-infection sleep characteristics affect risk of long COVID and to track changes in sleep duration during the year after SARS-CoV-2 infection.<br><br>METHODS: COVIDENCE UK is a prospective, population-based UK study of COVID-19 in adults. We included non-hospitalised participants with evidence of SARS-CoV-2 infection and used logistic regression to estimate adjusted ORs for the association between preinfection sleep characteristics and long COVID. We assessed post-infection sleep duration using multilevel mixed models. We collected sleep data from participants using a subset of questions from the Pittsburgh Sleep Quality Index. We defined long COVID as unresolved symptoms at least 12 weeks after infection. COVIDENCE UK is registered with ClinicalTrials.gov, NCT04330599.<br><br>RESULTS: We included 3994 participants in our long COVID risk analysis, of whom 327 (8.2%) reported long COVID. We found an inverse relationship between pre-infection sleep quality and risk of long COVID (medium vs good quality: OR 1.37, 95% CI 1.04 to 1.81; medium-low vs good: 1.55, 1.12 to 2.16; low vs good: 1.94, 1.11 to 3.38). Greater variability in pre-infection sleep efficiency was also associated with long COVID when adjusted for infection severity (OR per percentage-point increase 1.07, 1.02 to 1.12). We assessed post-infection sleep duration in 6860 participants, observing a 0.11&#x2009;hour (95%&#x2009;CI 0.09 to 0.14) increase in the first month after infection compared with pre-infection, with larger increases for more severe infections. After 1&#x2009;month, sleep duration largely returned to pre-infection levels, although fluctuations in duration lasted up to 6 months after infection among people reporting long COVID.<br><br>CONCLUSIONS: While poor-quality sleep before SARS-CoV-2 infection associates with increased risk of long COVID thereafter, changes in sleep duration after infection in these non-hospitalised cases were modest and generally quick to resolve.<br><br>TRIAL REGISTRATION NUMBER: NCT04330599.},
}
@article {pmid40517846,
year = {2025},
author = {López-Güell, K and Català, M and Dedman, D and Duarte-Salles, T and Kolde, R and López-Blasco, R and Martínez, &#xc1; and Mercier, G and Abellan, A and Arinze, JT and Burkard, T and Burn, E and Cuccu, Z and Delmestri, A and Delseny, D and Khalid, S and Kim, C and Kim, JW and Kostka, K and Loste, C and Mayer, MA and Meléndez-Cardiel, J and Mercadé-Besora, N and Mosseveld, M and Nishimura, A and Nordeng, HM and Oyinlola, JO and Paredes, R and Pérez-Crespo, L and Pineda-Moncusí, M and Ramírez-Anguita, JM and Trinh, NTH and Uusküla, A and Valdivieso, B and Prieto-Alhambra, D and Xie, J and Mateu, L and Jödicke, AM},
title = {Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries.},
journal = {Journal of clinical epidemiology},
volume = {185},
number = {},
pages = {111867},
doi = {10.1016/j.jclinepi.2025.111867},
pmid = {40517846},
issn = {1878-5921},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; Cluster Analysis ; Post-Acute COVID-19 Syndrome ; Databases, Factual ; Latent Class Analysis ; Adult ; SARS-CoV-2 ; Aged ; },
abstract = {OBJECTIVE: Prior evidence has suggested the multisystem symptomatic manifestations of post-acute COVID-19 condition (PCC). Here we conducted a network cluster analysis of 24 World Health Organization-proposed symptoms to identify potential latent subclasses of PCC.<br><br>STUDY DESIGN AND SETTING: Individuals with a positive test of or diagnosed with SARS-CoV-2 after September 2020 and with at least 1 symptom within &#x2265;90 to 365 days following infection were included. Subanalyses were conducted among people with &#x2265;3 different symptoms. Summary characteristics were provided for each cluster. All analyses were conducted separately in 9 databases from 7 countries, including data from primary care, hospitals, national health claims and national health registries, allowing to compare clusters across the different healthcare settings.<br><br>RESULTS: This study included 787,078 persons with PCC. Single-symptom clusters were common across all databases, particularly for joint pain, anxiety, depression and allergy. Complex clusters included anxiety-depression and abdominal-gastrointestinal symptoms.<br><br>CONCLUSION: Substantial heterogeneity within and between PCC clusters was seen across health-care settings. Current definitions of PCC should be critically reviewed to reflect this variety in clinical presentation.},
}
@article {pmid40516783,
year = {2025},
author = {Bravi, B and Paolini, M and Colombo, F and Palladini, M and Bettonagli, V and Mazza, MG and Lorenzo, R and Rovere-Querini, P and Benedetti, F and Poletti, S},
title = {Long term effect of COVID-19 on brain metabolism and connectivity.},
journal = {Neuroscience},
volume = {580},
number = {},
pages = {1-8},
doi = {10.1016/j.neuroscience.2025.06.015},
pmid = {40516783},
issn = {1873-7544},
mesh = {Humans ; *COVID-19/metabolism/diagnostic imaging/complications ; Male ; Female ; *Brain/metabolism/diagnostic imaging ; Middle Aged ; Adult ; *White Matter/metabolism/diagnostic imaging/pathology ; Aspartic Acid/analogs &amp; derivatives/metabolism ; Glutamic Acid/metabolism ; Magnetic Resonance Imaging ; SARS-CoV-2 ; Cognitive Dysfunction/metabolism/diagnostic imaging ; Neural Pathways/metabolism/diagnostic imaging ; },
abstract = {AIMS: After 3 years from the beginning of SARS-CoV-2 pandemic, a substantial proportion of affected patients still present at least one symptom after infection. Given that: magnetic resonance imaging studies up to two years after COVID-19 reported changes in white matter (WM) microstructure and in functional connectivity; WM associates with glutamate and N-acetyl-aspartate levels in BD; the link between cognitive impairment and WM integrity, the aim of the study was to investigate metabolites associations with alterations in structural and functional brain connectivity and cognition in 64 COVID-19 survivors and 33 healthy controls (HC).<br><br>METHODS: We compared WM microstructure and metabolites levels between individuals recovering from COVID-19 and HCs. Then, we investigated the associations between WM and glutamate and N-acetyl-aspartate in the two groups.<br><br>RESULTS: Patients showed: higher levels of glutamate and NAA compared to HCs with a positive effect on cognitive complaints; higher fractional anisotropy (FA), and lower radial (RD) and mean diffusivity (MD); glutamate and N-acetyl-aspartate significant positive associations with FA, and a negative one with MD and RD. FA levels moderated the relation between the glutamate and cognitive deficits. Finally, N-acetyl-aspartate associated with higher rs-FC between VOI and the posterior cingulate gyrus in individuals recovering from COVID-19.<br><br>CONCLUSIONS: Our findings suggest that a process of brain repair and remyelination, as suggested by higher levels of glutamate and N-acetyl-aspartate and by higher measures of WM microstructure, may occur after SARS&#x2011;CoV&#x2011;2 infection which may help the recovery from long COVID-19 symptoms such as cognitive impairment.},
}
@article {pmid40515424,
year = {2026},
author = {Thomas, C and Kudiersky, N and Ansdell, P and Ashton, RE and Brown, C and Bewick, T and Carr, J and Hume, E and Spillane, P and Pastorio, E and Owen, R and Maden-Wilkinson, T and McNeil-Angopa, E and Parkington, T and Arena, R and Ozemek, C and Formenti, F and Veluswamy, SK and Gururaj, R and Faghy, MA},
title = {Submaximal 2-day cardiopulmonary exercise testing to assess exercise capacity and post-exertional symptom exacerbation in people with long COVID.},
journal = {Experimental physiology},
volume = {111},
number = {2},
pages = {435-448},
pmid = {40515424},
issn = {1469-445X},
support = {IN-UK-983-6080//Gilead Sciences/ ; },
mesh = {Humans ; Female ; *COVID-19/physiopathology ; Middle Aged ; *Exercise Test/methods ; Male ; *Exercise Tolerance/physiology ; Oxygen Consumption/physiology ; Adult ; SARS-CoV-2 ; Exercise/physiology ; Heart Rate/physiology ; },
abstract = {Long COVID has a complex pathology and a heterogeneous symptom profile that impacts quality of life and functional status. Post-exertional symptom exacerbation (PESE) affects one-third of people living with long COVID, but the physiological basis of impaired physical function remains poorly understood. Sixty-eight people (age (mean ± SD): 50 ± 11 years, 46 females (68%)) were screened for severity of PESE and completed two submaximal cardiopulmonary exercise tests separated by 24 h. Work rate was stratified relative to functional status and was set at 10, 20 or 30 W, increasing by 5 W/min for a maximum of 12 min. At the first ventilatory threshold (VT1), V ̇ O 2 ${\dot V_{{{\mathrm{O}
}
_2}
}
}
$ was 0.73 ± 0.16 L/min on Day 1 and decreased on Day 2 (0.68 ± 0.16 L/min; P = 0.003). Work rate at VT1 was lower on Day 2 (Day 1 vs. Day 2; 28 ± 13 vs. 24 ± 12 W; P = 0.004). Oxygen pulse on Day 1 at VT1 was 8.2 ± 2.2 mL/beat and was reduced on Day 2 (7.5 ± 1.8 mL/beat; P = 0.002). The partial pressure of end tidal carbon dioxide was reduced on Day 2 (Day 1 vs. Day 2; 38 ± 3.8 vs. 37 ± 3.2 mmHg; P = 0.010). Impaired V ̇ O 2 ${\dot V_{{{\mathrm{O}
}
_2}
}
}
$ is indicative of reduced transport and/or utilisation of oxygen. V ̇ O 2 ${\dot V_{{{\mathrm{O}
}
_2}
}
}
$ at VT1 was impaired on Day 2, highlighting worsened function in the 24 h after submaximal exercise. The data suggest multiple contributing physiological mechanisms across different systems and further research is needed to investigate these areas.},
}
@article {pmid40514644,
year = {2025},
author = {Elboraay, T and Ebada, MA and Elsayed, M and Aboeldahab, HA and Salamah, HM and Rageh, O and Elmallahy, M and AboElfarh, HE and Mansour, LS and Nabil, Y and Eltawab, AKA and Atwan, H and Alkanj, S},
title = {Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {250},
pmid = {40514644},
issn = {1471-2377},
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; *Nervous System Diseases/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; Prevalence ; Fatigue/epidemiology ; },
abstract = {BACKGROUND: Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.<br><br>METHODS: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.<br><br>RESULTS: The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.<br><br>CONCLUSIONS: Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.<br><br>REGISTRATION AND PROTOCOL: This meta-analysis was registered in PROSPERO with registration number CRD42024576237.},
}
@article {pmid40514228,
year = {2025},
author = {Burrell, T and Simpson, A and Ramsenthaler, C and Crooks, MG and Johnson, MJ and Swan, F},
title = {Cool facial airflow hastens exertion recovery in chronic breathlessness: randomised crossover trial of different fan airflow speeds.},
journal = {BMJ supportive &amp; palliative care},
volume = {15},
number = {5},
pages = {633-641},
doi = {10.1136/spcare-2024-005103},
pmid = {40514228},
issn = {2045-4368},
mesh = {Humans ; Male ; Cross-Over Studies ; Female ; *Dyspnea/therapy/physiopathology ; Aged ; Prospective Studies ; Middle Aged ; Chronic Disease ; *Physical Exertion/physiology ; Pulmonary Disease, Chronic Obstructive ; Heart Rate ; Face ; },
abstract = {OBJECTIVES: Facial airflow from a hand-held fan (fan) hastens recovery from exertional breathlessness. We aimed to determine the effect of different airflow speeds on recovery from exertional breathlessness in patients with chronic breathlessness.<br><br>METHODS: A prospective, unblinded, randomised crossover trial. Participants with chronic breathlessness (modified Medical Research Council &#x2265; 3) completed five 1&#x2009;min sit-to-stand (STS) tests to induce breathlessness. After each STS test, participants used a fan with one of four airflow speeds or control (no fan) during 10&#x2009;min recovery. Numerical Rating Scale (NRS) breathlessness intensity, airflow pleasantness, heart rate, oxygen saturation and facial skin temperature were recorded.<br><br>RESULTS: 10 participants were recruited (n=1 withdrew due to health concerns) and 9 (mean&#xb1;SD&#x2009;age 66&#xb1;14 years; 5 men; 8 chronic obstructive pulmonary disease, 1 long covid) completed the trial. Per-protocol analysis identified no difference in NRS breathlessness recovery across fan speeds (p>0.05). Sensitivity analysis (n=1 excluded due to low exertional NRS breathlessness post STS test) identified a significant interaction effect for fan speed over time (p=0.010). Fan speed 2.85 m/s reduced NRS breathlessness compared with control at minutes 4-8 during recovery (p<0.05), whereas fan speeds 1.98 m/s, 3.70 m/s and 4.91 m/s only differed from control after 7&#x2009;min recovery (p<0.05). The perceived most pleasant and preferred airflow rate was 2.85 m/s. NRS pleasantness decreased with faster airflow speeds, suggesting a ceiling limit to net benefit.<br><br>CONCLUSION: Our novel data suggest the optimal airflow speed to hasten recovery from exertional breathlessness in people with chronic breathlessness is 2.85 m/s. Net benefit reduces at higher flow rates.},
}
@article {pmid40512699,
year = {2025},
author = {Khammawan, P and Thongprachum, A and Intawong, K and Chariyalertsak, S},
title = {Severity, mortality, long COVID-19, and quality of life: Insights from a cohort study of hospitalized COVID-19 patients during the delta variant predominance period in Thailand.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0324061},
pmid = {40512699},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/mortality/epidemiology/virology/pathology ; Thailand/epidemiology ; *Quality of Life ; Male ; Female ; Middle Aged ; Adult ; Aged ; SARS-CoV-2/isolation &amp; purification ; Hospitalization ; Severity of Illness Index ; Cohort Studies ; Anxiety ; Fatigue ; },
abstract = {BACKGROUND: The COVID-19 pandemic, declared in March 2020, has had significant global impacts, with Thailand reporting over 4.6 million cases and 32,000 fatalities by September 2022. Long COVID, or Post-COVID Conditions (PCC), affects 10-30% of COVID-19 patients globally, with symptoms lasting beyond three months. Common issues include fatigue, brain fog, respiratory problems, and psychological effects such as anxiety and depression. Symptoms can persist regardless of the initial infection severity, and ongoing research continues to refine understanding and management strategies. To address residual symptoms of COVID-19 during the Delta variant predominance period, a study was conducted from July to December 2021 at a tertiary care hospital in Chiang Mai, Thailand. The study aimed to describe the characteristics of COVID-19 patients, explore the Long COVID symptoms experienced by patients after discharge, and assess their quality of life.<br><br>METHODS: The study characterized 604 are moderate to severe COVID-19 patients at Tertiary Care Hospital during the Delta wave in Thailand (July-December 2021), using secondary data from medical records. Confirmed cases were cohort monitored using a Long COVID questionnaire for symptoms, chronic conditions, and social impact a year after discharge. Quality of life was evaluated using the SF-12 questionnaire (SF-12: 12-Item Short Form Survey). Long COVID, in this study, is defined as the persistence or emergence of one or more physical, psychological, or cognitive symptoms that last for more than 12 weeks after the initial onset of COVID-19 and cannot be explained by alternative diagnoses. This includes, but is not limited to, symptoms such as fatigue, dyspnea, chest pain, cough, cognitive dysfunction ("brain fog"), insomnia, anxiety, or depression.<br><br>FINDINGS: Most patients were Thai (85.9%) and female (57.3%), with obesity common among those aged 18-60 (48.3%). Severe cases and mortality were higher in patients over 60 (30.2%) and unvaccinated patients (60.4%). Severity was related with male gender, older age, lack of antiviral use, and being unvaccinated; overweight status, comorbidities, and abnormal chest x-rays were not significant. Deaths were influenced by gender, age, and antiviral use, but not hospital stay duration, overweight status, comorbidities, or vaccination status. At one-year follow-up, Long COVID symptoms were reported in a small proportion of patients (4.2% shortness of breath, 1.5% chronic cough), mostly in adults and older adults. Other symptoms were rare (<1%) and limited to the 18-60 age group. No severe neurological or systemic symptoms were reported. One-year post-hospitalization, 79.15% had no Long COVID symptoms. Quality of life scores were high (Physical Component Summary: PCS&#x2009;=&#x2009;48.62, Mental Component Summary: MCS&#x2009;=&#x2009;50.65).<br><br>INTERPRETATION: This study found a very low prevalence of Long COVID symptoms, which may be due to the severity of the Delta variant leading to higher mortality among patients with severe illness. Those who survived and recovered mostly had moderate symptoms and were predominantly under 60 years of age, which may explain the lower occurrence of Long COVID in this group. The majority of COVID-19 patients in Chiang Mai experienced moderate symptoms and had a high survival rate. Despite varied long COVID symptoms, most reported good physical and mental health one year after recovery. These findings highlight the resilience of patients and the importance of monitoring long-term health outcomes.},
}
@article {pmid40512228,
year = {2025},
author = {Goldenberg, DL},
title = {The pivotal role of central sensitization in long COVID, fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Expert review of neurotherapeutics},
volume = {25},
number = {8},
pages = {973-989},
doi = {10.1080/14737175.2025.2516097},
pmid = {40512228},
issn = {1744-8360},
mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/therapy ; *Fibromyalgia/physiopathology/therapy ; *COVID-19/physiopathology/complications/therapy ; *Central Nervous System Sensitization/physiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID is a condition characterized by persistent unexplained symptoms following COVID-19 infection. These symptoms are not related to another disease or organ damage and are similar to those in fibromyalgia and myslgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).<br><br>AREAS COVERED: The similar clinical and pathophysiological features and management of long COVID, fibromyalgia and ME/CFS are explored from the unifying framework of central sensitivity syndromes. The article is based on a literature search utilizing PubMed for content published between 2021 and 1 May 2025, using search terms: long COVID, long COVID syndrome, post-COVID-19, post-acute SARS-CoV-2, fibromyalgia, ME/CFS, post-exertional malaise and central sensitization.<br><br>EXPERT OPINION: Once long COVID is redefined to exclude patients with well-defined organ disease, it fits best as a model of central sensitization. Long COVID is a single syndrome, rather than many distinct diseases. Optimal management of long COVID and similar central sensitivity syndromes should include personalized care with a primary care led-multidisciplinary team.},
}
@article {pmid40511514,
year = {2025},
author = {Doehner, W and Schueller, PO},
title = {Comment on "Intermittent Hypoxic-Hyperoxic Training During Inpatient Rehabilitation Improves Exercise Capacity and Functional Outcome in Patients With Long Covid: Results of a Controlled Clinical Pilot Trial" by Doehner et al.-The Authors' Reply.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {3},
pages = {e13866},
pmid = {40511514},
issn = {2190-6009},
}
@article {pmid40511428,
year = {2025},
author = {Mistry, CP and Bhanderi, DJ},
title = {An Epidemiological Cross-sectional Study of Post-COVID-19 Syndrome in Patients of Anand District.},
journal = {Indian journal of community medicine : official publication of Indian Association of Preventive &amp; Social Medicine},
volume = {50},
number = {3},
pages = {486-499},
pmid = {40511428},
issn = {0970-0218},
abstract = {BACKGROUND: Coronavirus has infected 44.7 million Indians until December 2022. After recovery, patients are developing long-term effects of COVID-19. Research is required to know the burden of post-COVID-19 syndrome (PCS) and factors leading it. To estimate the prevalence of PCS and its associated factors in Anand district of Gujarat state. This cross-sectional study was conducted in 8 talukas of Anand district.<br><br>METHODS AND MATERIAL: Sample size of 450 patients divided into the hospitalized group and home/facility isolated group with samples of 300 and 150, respectively. Information was collected using a pretested semistructured questionnaire after taking written informed consent. It included demographic details, personal history, COVID-19-related information, and questions regarding persistent/newly developed symptoms after 12 weeks of COVID-19. The data collected were entered in Microsoft Excel 2019 and analyzed by SPSS version 15. Descriptive analysis followed by univariate analysis and logistic regression was performed. Among 450, 56% of patients were male and 43.3% were female.<br><br>RESULTS: The study reported 25.11% prevalence of PCS. Majority (82%) of patients having PCS had Grade I symptoms. Common symptoms recorded were weakness (10%) and breathlessness (4%). PCS was found to be associated with the hospitalization status of a patient, administration of drugs like antacids, Ivermectin, and Insulin.<br><br>CONCLUSIONS: Looking at current prevalence of PCS, well-sensitized healthcare system is needed to be established. Further research is required to explore more risk factors leading to PCS and various treatment options for PCS.},
}
@article {pmid40507911,
year = {2025},
author = {Popa, E and Popa, AE and Poroch, M and Poroch, V and Ungureanu, MI and Slanina, AM and Bacusca, A and Coman, EA},
title = {The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {11},
pages = {},
pmid = {40507911},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/metabolism ; *Cognitive Dysfunction/etiology/metabolism/virology ; SARS-CoV-2 ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; },
abstract = {Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood-brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-α) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic-pituitary-adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer's disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID.},
}
@article {pmid40507564,
year = {2025},
author = {Oesch-Régeni, B and Germann, N and Hafer, G and Schmid, D and Arn, N},
title = {The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies-A Pilot Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {11},
pages = {},
pmid = {40507564},
issn = {2077-0383},
abstract = {Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with not fully understood causes, though evidence points to immune system involvement and possible autoimmunity. ME/CFS could be triggered by various infectious pathogens, like SARS-CoV-2; furthermore, a subset of the post-COVID-19 condition (PCC) patients fulfill the diagnostic criteria of ME/CFS. According to the Canadian Consensus Criteria (CCC), the presence of specific symptoms such as fatigue, post-exertional malaise, sleep dysfunction, pain, neurological/cognitive manifestations, and symptoms from at least two of the following categories lead to the diagnosis of ME/CFS: autonomic, neuroendocrine, and immune manifestation. In this study, the patient selection was based on the identification of ME/CFS patients with elevated autoantibodies, regardless of the triggering factor of their condition. Methods: The aim of this study was to identify ME/CFS patients among long COVID patients with elevated autoantibodies. In seven cases, plasmapheresis (PE) and intravenous immunoglobulins (IVIGs) with repetitive autoantibody measurements were applied: four PE sessions on days 1, 5, 30, and 60, and a low-dose IVIG therapy after each treatment. Antibodies were measured before the first PE and two weeks after the last PE session. To monitor clinical outcomes, the following somatic and psychometric follow-up assessments were conducted before the first PE, 2 weeks after the second, and 2 weeks after the last PE: the Schellong test, ISI (insomnia), FSS (fatigue), HADS (depression and anxiety), and EQ-5D-5L (quality of life) questionnaires. Results: There was a negative association between both the β2-adrenergic and M3-muscarinic receptor autoantibody concentration and the quality of life measurements assessed with the EQ-5D-5L questionnaire. Per 1 U/mL increase in the concentration levels of β2-adrenergic receptor antibodies or M3-muscarinic acetylcholine receptor antibodies, the EQ-5D-5L index score [-0.59 to 1] decreased by 0.01 (0.63%) or 0.02 (1.26%), respectively. There were no significant associations between the ISI, HADS, and FSS questionnaires and the β1-adrenergic and M4-muscarinic receptor antibodies titers. Conclusions: After a thorough selection of patients with present autoantibodies, this pilot study found negative associations concerning autoantibody concentration and somatic, as well as psychological wellbeing. To validate these promising feasibility study results-indicating the potential therapeutic potential of antibody-lowering methods-further investigation with larger sample sizes is needed.},
}
@article {pmid40507431,
year = {2025},
author = {Fresi, E and Pagani, E and Pezzetti, F and Montomoli, C and Monti, C and Betti, M and De Silvestri, A and Sagliocco, O and Zuccaro, V and Bruno, R and Klersy, C},
title = {Long COVID's Hidden Complexity: Machine Learning Reveals Why Personalized Care Remains Essential.},
journal = {Journal of clinical medicine},
volume = {14},
number = {11},
pages = {},
pmid = {40507431},
issn = {2077-0383},
support = {code 2020-4238//CARIPLO Foundation/ ; },
abstract = {Background: Long COVID can develop in individuals who have had COVID-19, regardless of the severity of their initial infection or the treatment they received. Several studies have examined the prevalence and manifestation of symptom phenotypes to comprehend the pathophysiological mechanisms associated with these symptoms. Numerous articles outlined specific approaches for multidisciplinary management and treatment of these patients, focusing primarily on those with mild acute illness. The various management models implemented focused on a patient-centered approach, where the specialists were positioned around the patient. On the other hand, the created pathways do not consider the possibility of symptom clusters when determining how to define diagnostic algorithms. Methods: This retrospective longitudinal study took place at the "Fondazione IRCCS Policlinico San Matteo", Pavia, Italy (SMATTEO) and at the "Ospedale di Cremona", ASST Cremona, Italy (CREMONA). Information was retrieved from the administrative data warehouse and from two dedicated registries. We included patients discharged with a diagnosis of severe COVID-19, systematically invited for a 3-month follow-up visit. Unsupervised machine learning was used to identify potential patient phenotypes. Results: Three hundred and eighty-two patients were included in these analyses. About one-third of patients were older than 65 years; a quarter were female; more than 80% of patients had multi-morbidities. Diagnoses related to the circulatory system were the most frequent, comprising 46% of cases, followed by endocrinopathies at 20%. PCA (principal component analysis) had no clustering tendency, which was comparable to the PCA plot of a random dataset. The unsupervised machine learning approach confirms these findings. Indeed, while dendrograms for the hierarchical clustering approach may visually indicate some clusters, this is not the case for the PAM method. Notably, most patients were concentrated in one cluster. Conclusions: The extreme heterogeneity of patients affected by post-acute sequelae of SARS-CoV-2 infection (PASC) has not allowed for the identification of specific symptom clusters with the most recent statistical techniques, thus preventing the generation of common diagnostic-therapeutic pathways.},
}
@article {pmid40507399,
year = {2025},
author = {Diciolla, NS and Ampuero-López, A and Marques, A and Jiménez-Martín, A and García-De Villa, S and Torres-Lacomba, M and Yuste-Sánchez, MJ},
title = {Physical Activity and Sedentary Behaviour in People with Long COVID: A Follow-Up from 12 to 18 Months After Discharge.},
journal = {Journal of clinical medicine},
volume = {14},
number = {11},
pages = {},
pmid = {40507399},
issn = {2077-0383},
support = {FPI-UAH-20//Universidad de Alcal&#xe1;/ ; CPFM-2020/002_COVID19//Professional College of Physiotherapists of the Community of Madrid/ ; },
abstract = {Background/Objectives: Long-term effects of post-COVID-19 on several health outcomes remain unclear. We assessed PA and sedentary behaviour changes and explored behaviour-change factors twelve months post-COVID-19 in people with and without Long COVID. Methods: A prospective cohort study followed people treated for COVID-19 in different settings (home, hospital ward, intensive care unit) from twelve months to eighteen months post-COVID-19. Participants with and without Long COVID were identified. PA (Light PA-LPA, Moderate-to-Vigorous PA-MVPA, Steps·day[-1]), sedentary time, functional capacity (six-minute walk test-6MWT), muscle strength (quadriceps maximal voluntary contraction-QMVC), dyspnoea (modified Medical Research Council scale-mMRC), fatigue, symptoms of anxiety and depression, and health-related quality of life-HRQoL were assessed. Results: Among 148 participants (58 ± 15 years, 54% male), 101 had Long COVID. All remained physically inactive. People with Long COVID significantly increased LPA (LPALongCOVID +28 [1; 55] min·day[-1]; LPAControls +6 [-32; 45] min·day[-1]), and decreased MVPA (MVPALongCOVID -4 [-7; -2] min·day[-1]; MVPAControls -4 [-8; 1] min·day[-1]) and sedentarism (SedentarismLongCOVID -47 [-89; -4] min·day[-1]; SedentarismControls -30 [-88; 28] min·day[-1]). At eighteen months, higher proportions of individuals with Long COVID had impaired 6MWT (17% vs. 0%), reduced QMVC (25% vs. 6%), dyspnoea (24% vs. 0%), fatigue (67% vs. 13%), symptoms of anxiety (47% vs. 9%) and depression (26% vs. 0%) as well as poor HRQoL (50% vs. 6%). PA and sedentary behaviour changes at eighteen months were associated with dyspnoea and impaired QMVC at twelve months (LPA: mMRC ≥ 2: -41.56 [-129.30; 46.00] min·day[-1], Steps·day[-1]: mMRC: -416.13 [-1223.83; 391.57]; QMVC ≤ 70% predicted: -1251.39 [-2661.69; 158.91], Sedentarism: mMRC ≥ 2: +47.21 [-90.57; 184.99] min·day[-1]; 0.24 ≤ R[2] ≤ 0.32). Conclusions: PA and sedentary behaviour remain altered long after COVID-19, with people with Long COVID adjusting to fit lower PA levels, possibly driven by physical limitations and symptoms. Dyspnoea and muscle weakness may influence PA and sedentary behaviour.},
}
@article {pmid40507071,
year = {2025},
author = {Bigman, G and Rusu, ME and Shelawala, N and Sorkin, JD and Beamer, BA and Ryan, AS},
title = {A Comprehensive Scoping Review on Diet and Nutrition in Relation to Long COVID-19 Symptoms and Recovery.},
journal = {Nutrients},
volume = {17},
number = {11},
pages = {},
pmid = {40507071},
issn = {2072-6643},
support = {IK6 RX003977/RX/RRD VA/United States ; K01 AG078545/AG/NIA NIH HHS/United States ; P30 AG028747/AG/NIA NIH HHS/United States ; R01 AG051752/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/complications/physiopathology/diet therapy ; *Nutritional Status ; *Diet ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; },
abstract = {Background/Objectives: Long COVID-19 is characterized by persistent symptoms lasting three months or more following SARS-CoV-2 infection. Nutrition has emerged as a modifiable factor influencing recovery trajectories and symptom burden; however, existing evidence remains fragmented across diverse study designs and populations. This scoping review synthesized global evidence on the role of diet and nutrition in managing long COVID-19 symptoms and supporting recovery. Methods: Following PRISMA-ScR and Joanna Briggs Institute guidelines for scoping reviews, we searched major biomedical databases for studies published between 2020 and 2025. Eligible studies examined dietary intake, nutritional status, or nutrition-related interventions in adults with long COVID-19. Results: After duplicates were removed, 1808 records were screened, resulting in 50 studies that met the inclusion criteria-27 intervention studies and 23 observational studies. Nutritional exposures included micronutrients (e.g., vitamins D, K2), amino acids (e.g., L-arginine), multinutrient formulations, microbiota-targeted therapies (e.g., probiotics, synbiotics), nutritional status, diet quality, and whole-diet patterns (e.g., the Mediterranean diet). Approximately 76% of studies reported improvements in long COVID-19-related symptoms such as fatigue, mood disturbances, physical function, and markers of inflammation. Conclusions: Diet and nutrition may support long COVID-19 recovery by targeting inflammation and the gut microbiome to alleviate symptoms and improve functional outcomes. Well-powered trials of whole-diet approaches, combined with targeted supplementation, are needed to confirm their potential as scalable, accessible tools for post-COVID-19 recovery and management.},
}
@article {pmid40503046,
year = {2025},
author = {Shirani, K and Khorvash, F and Karamshahi, A and Maghamimehr, A},
title = {Investigating outcomes and treatment of long coronavirus disease 2019 in patients with multiple sclerosis treated with rituximab: A case series study.},
journal = {Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences},
volume = {30},
number = {},
pages = {26},
pmid = {40503046},
issn = {1735-1995},
abstract = {Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, characterized by the destruction of the myelin sheath of nerves. MS patients treated with rituximab, an immunosuppressive drug, experience reduced immunoglobulin levels, which increases their risk of various infections, including coronavirus disease 2019 (COVID-19). During the COVID-19 pandemic, many of these patients developed long-term symptoms following infection. These chronic symptoms have led to significant complications and, in some cases, increased mortality. In this case series study, we investigated long COVID-19 symptoms in MS patients treated with rituximab and the effects of intravenous immunoglobulin (IVIG) therapy in alleviating chronic symptoms. The results demonstrated that the patients' long-term symptoms responded to IVIG treatment, with significant improvements in respiratory symptoms, fever, immune parameters, and a reduction in C-reactive protein levels. This study highlights the importance of targeted management of long COVID-19 in immunocompromised populations and suggests that COVID-19 patients with immune deficiencies require specific therapeutic approaches.},
}
@article {pmid40502605,
year = {2025},
author = {Butzin-Dozier, Z and Ji, Y and Wang, LC and Anzalone, AJ and Hurwitz, E and Patel, RC and van der Laan, MJ and Colford, JM and Hubbard, AE},
title = {Causal Inference via Electronic Health Records in the National Clinical Cohort Collaborative: Challenges and Solutions in Long COVID Research.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40502605},
support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; 75N90023D00001/CL/CLC NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U01 DA055358/DA/NIDA NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; K01 AI182501/AI/NIAID NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; 75N99023D00001/OF/ORFDO NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; 75N95021D00001/DA/NIDA NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; 75N92023D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {Observational analyses of electronic health record (EHR) data using databases such as the National Clinical Cohort Collaborative include unique challenges for researchers seeking causal inferences, particularly when evaluating subjectively-defined outcomes like Long COVID. We explore several challenges and describe potential solutions. 1. Lack of true negatives: Many diagnoses and conditions either have a positive indicator or a missing status, requiring investigators to carefully consider which patients are likely negative for this condition. 2. Differential monitoring: EHR data include nonrandom missingness driven by patients engaging with the healthcare system at different rates, which is often related to both the exposure and outcome of interest. 3. Bias: EHR data sources face many biases, but are particularly vulnerable to informative missingness, differential monitoring, and model misspecification. 4. Large sample size: High precision (i.e., narrow confidence intervals) paired with potential bias leads to a high risk of incorrectly rejecting the null hypothesis. 5. Defining index time: It is important that investigators deliberately define index time (i.e., t 0 , baseline) to ensure that they only adjust for baseline confounders and do not adjust for (or condition on) factors that are affected by the exposure of interest (i.e., colliders or mediators). 6. Parameter selection: Investigators should only select parameters that are supported by the data distribution. This manuscript provides an overview of these challenges and solutions, using both simulated data and real-world data, with the outcome of Long COVID as the running example.},
}
@article {pmid40501971,
year = {2025},
author = {DeLine-Caballero, S and Ratnasiri, K and Chen, H and Sahagun, SJ and Mangalanathan, UM and Barnard, TR and Turk, N and Yang, J and Saini, N and Ayhan, EM and Memetimin, H and Finlin, BS and Leicht, Z and Kern, PA and Emery, I and Leeman, BM and Edelstein, GE and Costa, S and Choi, A and Li, JZ and Rosen, C and McLaughlin, T and Blish, CA},
title = {COVID-19 induces persistent transcriptional changes in adipose tissue that are not associated with Long COVID.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40501971},
issn = {2692-8205},
support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UM1 TR004921/TR/NCATS NIH HHS/United States ; },
abstract = {Long COVID is a heterogeneous condition characterized by a wide range of symptoms that persist for 90 days or more following SARS-CoV-2 infection. Now more than five years out from the onset of the SARS-CoV-2 pandemic, the mechanisms driving Long COVID are just beginning to be elucidated. Adipose tissue has been proposed as a potential reservoir for viral persistence and tissue dysfunction contributing to symptomology seen in Long COVID. To test this hypothesis, we analyzed subcutaneous adipose tissue (SAT) from two cohorts: participants with subacute COVID-19 (28-89 days post-infection) compared to pre-pandemic controls, and participants with Long COVID compared to those with those classified as "indeterminate" based on the RECOVER-Adult Long COVID Research Index (12-47 months post-infection). We found no evidence of persistent SARS-CoV-2 RNA in adipose tissue in any participant. SAT from participants with subacute COVID-19 displayed significant transcriptional remodeling, including depleted immune activation pathways and upregulated Hox genes and integrin interactions, suggesting resident immune cell exhaustion and perturbations in tissue function. However, no consistent changes in gene expression were observed between Long COVID samples and samples from indeterminant participants. Thus, SAT may contribute to inflammatory dysregulation following COVID-19, but does not appear to play a clear role in Long COVID pathophysiology. Further research is needed to clarify the role of adipose tissue in COVID-19 recovery.},
}
@article {pmid40500151,
year = {2025},
author = {Wei, Y and Horne, EM and Knight, R and Cezard, G and Walker, AJ and Fisher, L and Denholm, R and Taylor, K and Walker, V and Riley, S and Williams, DM and Willans, R and Davy, S and Bacon, S and Goldacre, B and Mehrkar, A and Denaxas, S and Greaves, F and Silverwood, RJ and Sheikh, A and Chaturvedi, N and Wood, AM and Macleod, J and Steves, C and Sterne, J and , },
title = {Patient characteristics associated with clinically coded long COVID: an OpenSAFELY study using electronic health records.},
journal = {BJGP open},
volume = {9},
number = {4},
pages = {},
pmid = {40500151},
issn = {2398-3795},
abstract = {BACKGROUND: Clinically coded long COVID cases in electronic health records (EHRs) are incomplete, despite reports of rising cases of long COVID.<br><br>AIM: To determine patient characteristics associated with clinically coded long COVID.<br><br>DESIGN &amp; SETTING: With the approval of NHS England, we conducted a cohort study using EHRs within the OpenSAFELY-TPP platform in England, to study patient characteristics associated with clinically coded long COVID from 29 January 2020 to 31 March 2022.<br><br>METHOD: We summarised the distribution of characteristics for people with clinically coded long COVID. We estimated age-sex adjusted hazard ratios (aHRs) and fully aHRs for coded long COVID. Patient characteristics included demographic factors, and health behavioural and clinical factors.<br><br>RESULTS: Among 17 986 419 adults, 36 886 (0.21%) were clinically coded with long COVID. Patient characteristics associated with coded long COVID included female sex, younger age (aged <60 years), obesity, living in less deprived areas, ever smoking, greater consultation frequency, and history of diagnosed asthma, mental health conditions, pre-pandemic post-viral fatigue, or psoriasis. These associations were attenuated following two doses of COVID-19 vaccines compared with before vaccination. Differences in the predictors of coded long COVID between the pre-vaccination and post-vaccination cohorts may reflect the different patient characteristics in these two cohorts rather than the vaccination status. Incidence of coded long COVID was higher in those with hospitalised COVID-19 than with those with non-hospitalised COVID-19.<br><br>CONCLUSION: We identified variation in coded long COVID by patient characteristic. Results should be interpreted with caution as long COVID was likely under-recorded in EHRs.},
}
@article {pmid40496870,
year = {2025},
author = {Talamini, L and Fonseca, DLM and Kanduc, D and Chaloin, O and Verdot, C and Galmiche, C and Dotan, A and Filgueiras, IS and Borghi, MO and Meroni, PL and Gavrilova, NY and Ryabkova, VA and Churilov, LP and Halpert, G and Lensch, C and Thurner, L and Fong, SW and Ng, LFP and Rénia, L and Young, BE and Lye, DC and Lozano, JM and Cabral-Marques, O and Shoenfeld, Y and Muller, S},
title = {Long COVID-19 autoantibodies and their potential effect on fertility.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1540341},
pmid = {40496870},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications ; *Autoantibodies/immunology/blood ; Male ; Female ; Animals ; *SARS-CoV-2/immunology ; Mice ; Spike Glycoprotein, Coronavirus/immunology ; *Fertility/immunology ; Adult ; Antibodies, Viral/immunology/blood ; Cross Reactions ; Middle Aged ; *Infertility, Male/immunology ; },
abstract = {Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. In silico approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and naïve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2-reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in in vitro experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients' fertility, suggesting a potential for autoimmune responses with human consequences.},
}
@article {pmid40496528,
year = {2024},
author = {Akbari, B and Wang, JM and Baghaei-Yazdi, N and Lahooti, H and Sherman, JH},
title = {Systems Thinking, Causal Loop Diagram, and Systems Dynamic in Public Health Challenges: Navigating Long COVID Syndrome and Sense of Smell in LGBTQIA+ Communities.},
journal = {Public health challenges},
volume = {3},
number = {3},
pages = {e70004},
pmid = {40496528},
issn = {2769-2450},
abstract = {BACKGROUND: The coronavirus pandemic has profoundly affected global health, economic stability, and environmental sustainability. Despite these challenges, significant gaps in data remain, particularly in effectively assessing and engaging diverse communities such as color, LGBTQIA+ individuals, and low-income groups. This shortage of comprehensive research limits our capacity to undertake sensitive studies, specifically in dealing with the complexities of long COVID, which some individuals continue to suffer from after their initial recovery.<br><br>OBJECTIVE: This review delves into the ongoing repercussions of long-term COVID-19, a postinfectious syndrome marked by neurological symptoms such as cognitive deficits and sensory impairments, which may last well beyond the acute phase of the illness. These symptoms frequently overlap with mental health issues (e.g., anxiety and depression), which can aggravate the socioeconomic challenges faced by vulnerable populations, especially within the LGBTQA+ communities.<br><br>METHODS: To tackle these complex interactions, we have introduced a novel public health framework: model-based systems thinking (MBST), which incorporates System Dynamics and causal loop diagrams (CLD).<br><br>RESULTS AND DISCUSSION: The articles were selected on the basis of their discussion of COVID-19-associated anosmia, exploration of olfactory dysfunction alongside neurocognitive disorders, and the challenges experienced in LGBQA+ communities. This approach offers a robust framework for dissecting the intricate ties between socioeconomic factors, health outcomes, and the extended recovery trajectories associated with long-term COVID-19, with a particular focus on olfactory dysfunction. We also explore strategies to make our models more accessible to healthcare providers and the LGBTQA+ communities, encouraging its broader adoption.<br><br>CONCLUSION: Long COVID's impact on public health and marginalized communities highlights the urgent need for adopting systems thinking models. Additionally, this article calls for a concerted effort from all experts to foster multidisciplinary, team-based research and implement effective support measures for COVID-19 survivors across all communities, mainly focusing on the scientific, social, and behavioral challenges LGBTQIA+ and low-income individuals face.},
}
@article {pmid40495312,
year = {2025},
author = {Lai, CL and Wei, LC and Chiu, HJ},
title = {Expanding Perspectives on Long COVID: Multisystem Outcomes, Socioeconomic Factors, and Occupational Implications.},
journal = {American journal of industrial medicine},
volume = {68},
number = {8},
pages = {724-725},
doi = {10.1002/ajim.23744},
pmid = {40495312},
issn = {1097-0274},
support = {//The authors received no specific funding for this work./ ; },
}
@article {pmid40492581,
year = {2025},
author = {Vlaming-van Eijk, LE and Tang, G and Bourgonje, AR and den Dunnen, WFA and Hillebrands, JL and van Goor, H},
title = {Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies.},
journal = {The Journal of pathology},
volume = {266},
number = {4-5},
pages = {369-389},
pmid = {40492581},
issn = {1096-9896},
mesh = {Humans ; *COVID-19/complications/therapy/physiopathology/pathology ; Phenotype ; SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; },
abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID-19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient-tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS-CoV-2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS-CoV-2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.},
}
@article {pmid40492405,
year = {2025},
author = {Luker, S and Doveton, A and Manuel, K and Adey-Wakeling, Z and Jaggard, D and Crotty, M and Cameron, ID and Karnon, J and McNaughton, H and Ullah, S and Laver, K},
title = {Take charge after long COVID: a mixed methods randomised controlled pilot study protocol.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2516694},
pmid = {40492405},
issn = {1365-2060},
mesh = {Humans ; *COVID-19/rehabilitation/complications ; Pilot Projects ; Randomized Controlled Trials as Topic ; Prospective Studies ; SARS-CoV-2 ; *Self-Management/methods ; },
abstract = {INTRODUCTION: Post COVID-19 condition is a debilitating illness with over 200 symptoms across 10 organ systems and is presently impacting millions worldwide. The National Institute for Health and Care Excellence recommends a multidisciplinary treatment approach including person-centred self-management strategies, however evidence for specific programs is lacking. The Take Charge intervention is a person-centred, self-management rehabilitation approach that has been effective in recovery after stroke, but not yet tested in post COVID-19 condition.<br><br>METHODS &amp; ANALYSIS: A prospective, single-centre, parallel, 2 group, mixed methods, randomized controlled trial with embedded process evaluation of the Take Charge intervention in individuals living with post COVID-19 condition. Participants will be at least 18&#x2009;years of age, have a confirmed diagnosis of post COVID-19 condition with ongoing symptoms, and be known to a hospital clinic for assessment and treatment of patients with post-acute sequelae of COVID-19. The primary outcomes are the Modified COVID-19 Yorkshire Rehabilitation Scale and the COVID-19 Core Outcome Measure for Recovery. The secondary outcomes include physical and self-report measures, and feasibility measures. Qualitative interviews will also be conducted to understand the clinicians' and participants' experiences. Statistical analysis will be performed on an intention-to-treat basis using a multivariate mixed-effect linear regression model.<br><br>ETHICS &amp; DISSEMINATION: This study adheres to the Declaration of Helsinki. This study was approved by the Southern Adelaide Clinical Human Research Ethics Committee (approval number: 2022/SSA00695/OFR: 219.22, protocol version 3.3 19 February 2024). The results will be disseminated in peer-reviewed journals, conference presentations, and media.},
}
@article {pmid40491436,
year = {2025},
author = {Li, D and Zhang, DY and Chen, SJ and Lv, YT and Huang, SM and Chen, C and Zeng, F and Chen, RX and Zhang, XD and Xiong, JX and Chen, FD and Jiang, YH and Chen, Z and Mo, CY and Chen, JJ and Zhu, XL and Zhang, LJ and Bai, FH},
title = {Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1565887},
pmid = {40491436},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/microbiology ; *Gastrointestinal Microbiome ; *Fungi/classification/genetics/isolation &amp; purification ; Female ; *Bacteria/classification/genetics/isolation &amp; purification ; Male ; Adult ; Middle Aged ; Feces/microbiology ; SARS-CoV-2 ; *Mycobiome ; Probiotics ; Metagenomics ; China ; },
abstract = {OBJECTIVE: COVID-19 has had a profound impact on public health globally. However, most studies have focused on patients with long COVID or those in the acute phase of infection, with limited research on the health of individuals who have recovered from mild COVID-19. This study investigates the long-term changes in bacterial and fungal communities in individuals recovering from mild COVID-19 and their clinical relevance.<br><br>METHODS: Healthy individuals from Hainan Province were enrolled before the COVID-19 outbreak, along with individuals recovering from COVID-19 at 3 months and 6 months post-recovery. Stool, blood samples, and metadata were collected. Metagenomic sequencing and Internal Transcribed Spacer (ITS) analysis characterized bacterial and fungal communities, while bacterial-fungal co-occurrence networks were constructed. A random forest model evaluated the predictive capacity of key taxa.<br><br>RESULTS: The gut microbiota of COVID-19 recoverees differed significantly from that of healthy individuals. At 3 months post-recovery, probiotics (e.g., Blautia massiliensis and Kluyveromyces spp.) were enriched, linked to improved metabolism, while at 6&#xa0;months, partial recovery of probiotics (e.g., Acidaminococcus massiliensis and Asterotremella spp.) was observed alongside persistent pathogens (e.g., Streptococcus equinus and Gibberella spp.). Dynamic changes were observed, with Acidaminococcus massiliensis enriched at both baseline and 6 months but absent at 3 months. Co-occurrence network analysis revealed synergies between bacterial (Rothia spp.) and fungal (Coprinopsis spp.) taxa, suggesting their potential roles in gut restoration. The bacterial random forest model (10 taxa) outperformed the fungal model (8 taxa) in predicting recovery status (AUC = 0.99 vs. 0.80).<br><br>CONCLUSION: These findings highlight the significant long-term impacts of mild&#xa0;COVID-19 recovery on gut microbiota, with key taxa influencing metabolism and immune regulation, supporting microbiome-based strategies for recovery management.},
}
@article {pmid40491049,
year = {2025},
author = {Nlandu, YM and Makulo, JR and Essig, M and Engole, YM and Mboliasa, MI and Nkodila, AN and Mokoli, VM and Nkondi, CN and Longo, AL and Kajingulu, FM and Ilunga, CK and Zinga, CV and Kadima, EM and Bukabau, JB and Ahuka, SM and Lumaka, A and Nseka, NM and Sumaili, EK},
title = {Longitudinal kidney outcomes in surviving COVID-19 patients in Africa: a prospective Congolese single-center cohort study.},
journal = {Renal failure},
volume = {47},
number = {1},
pages = {2514185},
pmid = {40491049},
issn = {1525-6049},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Middle Aged ; Prospective Studies ; *Renal Insufficiency, Chronic/epidemiology/physiopathology/etiology ; *Acute Kidney Injury/epidemiology/physiopathology/etiology ; Glomerular Filtration Rate ; Incidence ; Aged ; Adult ; SARS-CoV-2 ; Intensive Care Units ; Longitudinal Studies ; Risk Factors ; Creatinine/blood ; },
abstract = {OBJECTIVES: The aim of this study was to determine kidney outcomes and associated factors in COVID-19 patients discharged from intensive care unit (ICU) in an African setting.<br><br>METHODS: In a prospective observational single-center cohort study, we compared the rate of decline in eGFRcr and the incidence of CKD between COVID-19 patients with and without AKI after discharge from ICU. Kidney function decline (KFD) and chronic kidney disease (CKD) during 2&#x2009;years of follow-up were defined as eGFR decline &#x2265; 30% and eGFR less than 60&#x2009;mL/min/1.73 m[2] and/or the presence of proteinuria, respectively. The association between COVID-19-associated AKI (COVID-AKI) and eGFR decline after hospital discharge was assessed using mixed-effects models. Logistic regression and Cox regression were used to define factors associated with KFD and CKD.<br><br>RESULTS: The incidence of KFD and CKD at two years of follow-up was 23% and 0.73 per 100 patient months (P-M), respectively. Patients with COVID-AKI had a greater decline in eGFR (-11.09&#x2009;mL/min/1.73 m[2]/year [95% CI, -3.65 to-1.02]; p &#x2c2;0.001) and CKD incidence (3.11 per 100&#x2009;P-M vs 0.18 per 100&#x2009;P-M, p&#x2009;=&#x2009;0.003) in the fully adjusted model controlling for comorbidities and peak creatinine level. AKI was associated with KFD (aOR: 3.46 [2.40-5.24], p&#x2009;=&#x2009;0.001) and CKD (aHR: 3.37 [2.35-5.41], p&#x2009;=&#x2009;0.003).<br><br>CONCLUSION: KFD and CKD are common in COVID-19 survivors. AKI was associated with both KFD and CKD after ICU discharge. Kidney care after COVID-19 needs to be organized in the context of AKI.},
}
@article {pmid40489988,
year = {2025},
author = {Venkatesan, P},
title = {US Government cuts funding for long COVID research.},
journal = {The Lancet. Microbe},
volume = {},
number = {},
pages = {101166},
doi = {10.1016/j.lanmic.2025.101166},
pmid = {40489988},
issn = {2666-5247},
}
@article {pmid40488309,
year = {2025},
author = {Bennett, J and Jeffreys, M and Waa, A and Zhang, J and Brooks, AES and Hockey, L and Kvalsvig, A and Baker, MG},
title = {Post-Covid-19 Symptoms in Children: A Cross-Sectional Survey.},
journal = {Journal of paediatrics and child health},
volume = {61},
number = {8},
pages = {1279-1286},
pmid = {40488309},
issn = {1440-1754},
support = {//Ministry of Health, New Zealand/ ; },
mesh = {Humans ; *COVID-19/epidemiology/complications ; Cross-Sectional Studies ; Child ; Male ; Adolescent ; Female ; Child, Preschool ; New Zealand/epidemiology ; Young Adult ; SARS-CoV-2 ; Health Status ; Health Surveys ; Self Report ; },
abstract = {AIM: To assess children's self or parental-rated health following Aotearoa New Zealand's (NZ) first widespread community transmission of SARS-CoV-2 in February 2022.<br><br>METHODS: This cross-sectional study recruited participants aged 3-20&#x2009;years who had consented to be contacted after taking part in the NZ Health Survey. Participants over 15&#x2009;years or guardians of younger children were surveyed by telephone between November 2022 and April 2023. Ordinal logistic regression was used to estimate the effect of Covid-19 infection on self-reported health.<br><br>RESULTS: The study included 4264 children and young adults, with 70.6% reporting having tested positive for Covid-19 at least once (via PCR or RAT test). Almost one-quarter (24.5%) reported more frequent coughs, colds and stomach bugs after Covid-19 infection. One-fifth reported headaches (21.7%), fatigue (20.6%) or stomach aches (14.6%) and 13.1% reported anxiety that was new since having Covid-19. At baseline, there were no significant differences between the self-rated health status of those children who later had Covid-19 and those who did not (p&#x2009;=&#x2009;0.5274). Following widespread SARS-CoV-2 transmission, those who reported having had Covid-19 were significantly more likely to report a poorer health status than those who did not (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: Greater than one-fifth of NZ children reported persisting symptoms after Covid-19 infection. Post-Covid-19 symptoms impacted the quality of children's day-to-day lives. Preventing infection is key to preventing post-Covid-19 symptoms.},
}
@article {pmid40488276,
year = {2025},
author = {Liu, JK and Zhou, ZS and Wang, SH and Zuo, SY and Lu, XF and He, Y and Tang, H and Xie, Y and Xie, MX and Zhang, XL},
title = {SARS-CoV-2 N protein interacts with Na v 1.7 to promote pathological pain.},
journal = {Pain},
volume = {166},
number = {11},
pages = {e635-e651},
doi = {10.1097/j.pain.0000000000003675},
pmid = {40488276},
issn = {1872-6623},
mesh = {Animals ; Ganglia, Spinal/metabolism ; Mice ; Humans ; *Coronavirus Nucleocapsid Proteins/metabolism ; *COVID-19/metabolism/complications ; SARS-CoV-2/metabolism ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Neurons/metabolism ; Female ; *Pain/metabolism ; *Voltage-Gated Sodium Channels/metabolism ; *Phosphoproteins/metabolism ; },
abstract = {Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis, with many patients experiencing not only acute neurological and sensory symptoms but also persistent sensory abnormalities, commonly referred to as long COVID sequelae. The mechanisms underlying somatosensory abnormalities induced by SARS-CoV-2 remain largely unclear. In this study, we investigate the role of the SARS-CoV-2 nucleocapsid (N) protein in pain regulation. Our data show that SARS-CoV-2 N protein exacerbates pathological pain in mouse models of bone cancer, chemotherapy, neuropathic, and inflammatory, and promotes the chronification of acute inflammatory pain. We also identify a potential interaction between the N protein and Na v 1.7 in dorsal root ganglion neurons from mice, monkeys, and humans. Furthermore, the N protein significantly increases Na v 1.7 currents in dorsal root ganglion neurons from both mice and monkeys by delaying Na v 1.7 inactivation without altering its expression or membrane trafficking. This modulation of Na v 1.7 function by the N protein not only intensifies pain hypersensitivity but also prolongs the duration of pain, potentially facilitating the transition from acute to chronic pain. Our findings underscore the importance of vigilant management of SARS-CoV-2 infection in patients with pathological pain and suggest potential therapeutic targets for mitigating COVID-19-related pain.},
}
@article {pmid40485204,
year = {2025},
author = {Crea, F},
title = {Focus on trials: interventional cardiology, ischaemic heart disease, and long COVID.},
journal = {European heart journal},
volume = {46},
number = {22},
pages = {2037-2041},
doi = {10.1093/eurheartj/ehaf339},
pmid = {40485204},
issn = {1522-9645},
}
@article {pmid40485161,
year = {2025},
author = {O'Donnell, AN},
title = {Contextualizing Long COVID.},
journal = {American journal of health promotion : AJHP},
volume = {39},
number = {6},
pages = {951-953},
doi = {10.1177/08901171241308066},
pmid = {40485161},
issn = {2168-6602},
}
@article {pmid40485160,
year = {2025},
author = {Conard, S and Cunningham-Hill, M and Kusti, M and Mukherji, S and Rawlins, W and Schwartz, S and , },
title = {Employers' Long Game for Long Covid.},
journal = {American journal of health promotion : AJHP},
volume = {39},
number = {6},
pages = {965-968},
doi = {10.1177/08901171241308066c},
pmid = {40485160},
issn = {2168-6602},
}
@article {pmid40485158,
year = {2025},
author = {Unger, ER},
title = {Long COVID as an Infection-Associated Chronic Condition: Implications.},
journal = {American journal of health promotion : AJHP},
volume = {39},
number = {6},
pages = {960-965},
pmid = {40485158},
issn = {2168-6602},
support = {CC999999/ImCDC/Intramural CDC HHS/United States ; },
abstract = {A link between infection and chronic illness has been recognized, along with the complexities of interactions between pathogen, environment, host genetics, route of exposure, and timing of outcomes. The COVID-19 pandemic has brought this issue to the forefront and Long COVID is recognized to be an infection associated chronic condition. However, given the wide range of Long COVID presentations, the singular expression gives a false sense of simplicity. Long COVID is best considered as a group of infection associated conditions requiring developing research studies and treatment trials that address the inherent heterogeneity.},
}
@article {pmid40485157,
year = {2025},
author = {O'Donnell, AN and Berghaus, M and Simon, ID},
title = {Long COVID: Context, Considerations, and Calls for Change.},
journal = {American journal of health promotion : AJHP},
volume = {39},
number = {6},
pages = {953-960},
doi = {10.1177/08901171241308066a},
pmid = {40485157},
issn = {2168-6602},
}
@article {pmid40485127,
year = {2025},
author = {Felton, L and Kalfas, M and Brewin, D and Beckwith, C and Khan, T and Jolley, C and Hart, N and Duncan, EL and Nicholson, T and Witard, O and Moore, J and Metcalfe, A and Rafferty, GF and Chalder, T},
title = {Codeveloping a Novel Intervention for People With Post-COVID Condition: The Balance-ACT Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70320},
pmid = {40485127},
issn = {1369-7625},
support = {//This research was funded Guy's and St Thomas' Charity (COV210803). T.C. is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at a UK NHS Foundation Trust and received additional COVID-related grants from UKRI. E.L.D. has received funding for research into Long COVID from the Chronic Disease Research Foundation, specifically for the genetics of PCS/ongoing symptomatic COVID-19. Has also received funding from the BMA Foundation and Guy's and St Thomas' Charity for Long COVID-related research. C.J. has received funding from the BMA Foundation for research into Long COVID./ ; },
mesh = {Humans ; *COVID-19/complications/psychology ; Qualitative Research ; *Acceptance and Commitment Therapy/methods ; Female ; Male ; Fatigue/therapy/etiology ; Middle Aged ; SARS-CoV-2 ; Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Some people experience persistent symptoms, such as fatigue, brain fog and breathlessness, long after the onset of COVID-19 infection. This is known as the post-COVID syndrome (PCS). We developed a unique and holistic psycho-physiological intervention that integrates Acceptance and Commitment Therapy (ACT), a structured talking therapy, with principles of homeostasis. This aims to provide targeted support and treatment strategies for effectively managing the long-term repercussions of the condition and improve patient outcomes.<br><br>METHODS: This empirical study was informed by theory and other research strands. These strands included a qualitative study of people with lived experience, a scoping review of interventions for fatigue (including rehabilitation) and insights from a patient and public involvement (PPI) group. The PPI group were actively involved in the development of the intervention, manuals and overall study management, ensuring it was relevant, ethical and aligned with patient preferences and needs.<br><br>RESULTS: The qualitative study uncovered the tangible contexts in which the intervention would be implemented, and the attraction of Balance-ACT for those living with PCS. People living with PCS (n&#x2009;=&#x2009;19) and health care professionals (HCPs; n&#x2009;=&#x2009;12) provided overall endorsement for the intervention. Through an iterative process, their feedback, alongside input from the PPI group, informed the development of key materials, including a therapist manual, participant handbook, mindfulness recordings and an animation. Therapists were trained, and a novel fidelity measure was developed to ensure adherence to Balance-ACT principles.<br><br>CONCLUSION: We used an iterative approach to develop the Balance-ACT intervention, which was acceptable to patients and HCPs. Subsequent research will examine the efficacy of Balance-ACT.<br><br>This article represents work conducted as part of the Balance-ACT project. People with the post-COVID condition (PCC) were involved throughout all aspects of this study, in line with the National Institute for Health and Care Research framework, and contributed in several key ways. It ensured the research captured a diverse range of illness experiences. The study design was refined and addressed potential barriers to engagement. Patient-friendly language was used to improve accessibility, making the study more inclusive. Additionally, the outcome measures were informed by patient input to enhance their relevance. Finally, dissemination was guided to ensure that the findings were both useful and accessible, using clear language in reporting and incorporating feedback from patient representatives on drafts to ensure clarity. C.B. recorded the mindfulness exercises and was a core part of the management team throughout.},
}
@article {pmid40485056,
year = {2025},
author = {Ribeiro-Carvalho, A and Prado, MF and Marcelo, GG and Viveiros, L and de Andrade Fernandes, M and Nórte, CE},
title = {Cognitive and Emotional Health in Long COVID: a Cross-Sectional Study in Brazil.},
journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists},
volume = {40},
number = {8},
pages = {1473-1482},
doi = {10.1093/arclin/acaf054},
pmid = {40485056},
issn = {1873-5843},
mesh = {Humans ; Female ; *COVID-19/complications/psychology/epidemiology ; Brazil/epidemiology ; Cross-Sectional Studies ; Male ; Middle Aged ; Adult ; *Cognitive Dysfunction/epidemiology/etiology ; Aged ; *Depression/epidemiology/etiology ; Neuropsychological Tests ; Anxiety ; Mental Health ; },
abstract = {OBJECTIVE: Long COVID is characterized by persistent symptoms following a COVID-19 infection, including cognitive and emotional impairment. Brazil has one of the highest rates of COVID-19 infections globally, but there are still few studies assessing the long-term impact of the disease on mental health in this population. In the present study, we evaluated cognition and emotional symptoms in patients with cognitive complaints after COVID infection in Rio de Janeiro, Brazil.<br><br>METHOD: Cognitive and emotional assessments were performed individually (n&#x2009;=&#x2009;114) using the Cognitive Screening (TRIACOG) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) in participants with long COVID. Of the total subjects, 78% were women, with a mean age of 50.4&#x2009;&#xb1;&#x2009;16&#xa0;years. A total of 72.6% received treatment at home, whereas 28% were hospitalized during the acute phase of the infection.<br><br>RESULTS: Our data revealed a high prevalence of cognitive and emotional impairment. Approximately 66.7% exhibited symptoms suggestive of depression, 55.9% anxiety disorder, and 65.7% stress. Notably, executive functions and memory were the most affected cognitive domains. Intriguingly, the time from infection onset to assessment did not appear to influence cognitive performance, suggesting that cognitive impairment associated with COVID-19 may persist as a long-term comorbidity. Furthermore, hospitalization did not affect cognitive or DASS-21 scores.<br><br>CONCLUSIONS: These findings underscore the importance of investigating the long-term impacts of COVID-19 on mental health. Assessing emotional and cognitive functions after COVID-19 is crucial for developing therapeutic responses, both on an individual level and from a public health perspective.},
}
@article {pmid40483989,
year = {2025},
author = {Mendenhall, E and Banerjee, S and Wahlberg, A},
title = {Interembodiment among Long Haulers and their carers.},
journal = {Social science &amp; medicine (1982)},
volume = {381},
number = {},
pages = {118282},
doi = {10.1016/j.socscimed.2025.118282},
pmid = {40483989},
issn = {1873-5347},
mesh = {Humans ; *Caregivers/psychology ; Female ; Chronic Disease/psychology ; COVID-19/psychology ; Male ; Qualitative Research ; Middle Aged ; },
abstract = {Millions of people around the world experience the lingering disabling health effects of the pandemic, rendering new forms of chronic living. Chronic living is an interembodied experience, where people attend to, experience, and take care of themselves and their medical conditions with the indispensable help of loved ones, in differing life conditions, and with stratified access to (lifesaving) medical treatment and care. We suggest that this form of chronicity inherently involves caregivers who experience chronic disruption and dynamism. Nested within a study of Long Haulers involving more than 100 interviews, we draw from three case studies that illuminate an interdependence among patients and their carers where not only their social lives are mutually reinforced with others but their bodies are, too. We employ a theory of interembodiment to reveal how sick roles become essential elements of everyday life that are emotional, material, social and biological. Our first case study reveals an intergenerational connection between a Long Hauler and her children who are also living with the condition. The second case reveals how deeply illness is embodied among and between a Long Hauler and her caretaker who is battling cancer-both whose health futures remain uncertain. The third case how a Long Hauler who cares for her son with dementia receives support and legitimacy from a digital community. These examples demonstrate various forms of interembodiment that become realized in chronic living as people ill from Long Covid navigate the layers of support in the home, community, and clinic. As a consequence, people living with complex chronic conditions like Long Covid often - and ironically - must expend considerable amounts of energy in trying to have their condition acknowledged, treated, and cared for when engaging with family, friends, employers or healthcare professionals.},
}
@article {pmid40483738,
year = {2025},
author = {Aldujeli, A and Tsai, TY and Haq, A and Puipaite, K and Braukyliene, R and Tatarunas, V and Zaliaduonyte, D and Unikas, R and Renkens, M and Revaiah, PC and Miyashita, K and Tobe, A and Oshima, A and Sharif, F and Lesauskaite, V and Spertus, JA and Garg, S and Onuma, Y and Brilakis, ES and Serruys, PW},
title = {Impact of severe COVID-19 infection on coronary microvascular dysfunction in ANOCA patients: A cross-sectional study.},
journal = {Atherosclerosis},
volume = {407},
number = {},
pages = {120389},
doi = {10.1016/j.atherosclerosis.2025.120389},
pmid = {40483738},
issn = {1879-1484},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Angina Pectoris/physiopathology/epidemiology ; *Coronary Artery Disease/physiopathology/epidemiology ; *Coronary Circulation ; *Coronary Vessels/physiopathology ; *COVID-19/complications/physiopathology/epidemiology/diagnosis ; Cross-Sectional Studies ; Exercise Test ; Incidence ; *Microcirculation ; Prospective Studies ; SARS-CoV-2 ; Severity of Illness Index ; },
abstract = {BACKGROUND AND AIMS: Millions of survivors from severe COVID-19 infection suffer from residual symptoms including anginal chest pain. The pathophysiological mechanisms, particularly the role of coronary microvascular dysfunction (CMD), however, remain elusive. We compared the incidence and endotypes of CMD in patients with angina without obstructive coronary artery disease (ANOCA) between those who had a history of severe COVID-19 infection (COVID group, defined as COVID patients needing supplemental oxygen therapy with SpO2 < 90 % on room air), versus those who didn't (Control group).<br><br>METHODS: This multicentre, prospective cohort study enrolled 117 ANOCA patients (COVID group n&#xa0;=&#xa0;59, Control group n&#xa0;=&#xa0;58). All participants underwent exercise stress testing and invasive coronary physiology assessment to measure coronary flow reserve (CFR), and the index of microvascular resistance (IMR). CMD was defined as CFR<2.0 or IMR&#x2265;25. Patients also completed the modified Seattle Angina Questionnaire (SAQ-7) after invasive functional assessment.<br><br>RESULTS: CMD was diagnosed in 42 patients (35.9&#xa0;%): 47.5&#xa0;% in the COVID group and 24.1&#xa0;% in the Control group (p&#xa0;=&#xa0;0.015). The prevalence of structural CMD was significantly higher in the COVID group (28.8&#xa0;% vs. 5.2&#xa0;%, p&#xa0;<&#xa0;0.001). The median IMR was significantly higher in the COVID versus the Control group (20.00 [15.00, 42.00] vs. 17.00 [12.00, 21.00], p&#xa0;=&#xa0;0.002) while no significant differences were observed in CFR and FFR. The SAQ-7 summary scores (54.44 vs. 59.44, p&#xa0;=&#xa0;0.003) and physical limitation and quality-of-life domain scores were all significantly lower in the COVID group.<br><br>CONCLUSIONS: The incidence of CMD, particularly structural CMD, was higher in ANOCA patients with a history of severe COVID-19 infection, suggesting a link between persistent angina and CMD in this population.},
}
@article {pmid40482860,
year = {2025},
author = {Baalbaki, N and Blankestijn, JM and Kazer, SW and Abdel-Aziz, MI and Bloemsma, LD and Bogaard, HJ and Cornelissen, MEB and van Drunen, CM and van Egmond, D and Nossent, EJ and Walsh, JML and Ordovas-Montanes, J and Golebski, K and Maitland-van der Zee, AH and , },
title = {Toward precision medicine: Inflammatory nasal epithelial transcriptomic profiles in long COVID.},
journal = {The Journal of allergy and clinical immunology},
volume = {156},
number = {3},
pages = {790-802},
doi = {10.1016/j.jaci.2025.05.023},
pmid = {40482860},
issn = {1097-6825},
mesh = {Humans ; *COVID-19/genetics/immunology ; *Nasal Mucosa/immunology/metabolism/pathology ; Male ; Female ; *Transcriptome ; *SARS-CoV-2 ; Middle Aged ; Precision Medicine ; Inflammation/genetics ; Aged ; Adult ; Gene Expression Profiling ; Cohort Studies ; },
abstract = {BACKGROUND: Little is known about the role of the nasal epithelium in long COVID (LC).<br><br>OBJECTIVE: We sought to assess nasal epithelial transcriptomes of patients with LC to unravel pathophysiological mechanisms for disease management.<br><br>METHODS: Medical data and transcriptomes were obtained from participants in the Precision Medicine for More Oxygen COVID-19 cohort at 3 to 6 months (n = 40) and at 12 to 18 months (n = 15) post-COVID. Cell-type frequencies were estimated by deconvolution from a single-cell data set. Hierarchical clustering identified transcriptomic clusters and cellular clusters from which differences in gene expression, gene set enrichment, and pulmonary phenotypes were assessed. Functional validation was performed using CRISPR/Cas9 gene editing and in vitro assays in primary mutant nasal epithelium, and gene expression comparisons were made with healthy controls (n = 51).<br><br>RESULTS: At 3 to 6 and 12 to 18 months, transcriptomes associated with inflammatory pathways (Padj < .05). Transcriptomic and cellular clusters were identified and were related to inflammation and ciliogenesis (Padj < .05). Comparison of transcriptomes of patients with and without pulmonary radiological abnormalities resulted in 613 significant differentially expressed genes (Padj < .05). Upregulated inflammatory genes were observed in patients with abnormalities. SMURF1 expression was significantly increased in patients with abnormalities compared with those without abnormalities and healthy controls. SMURF1[-/-] mutant nasal epithelial cells produced significantly lower levels (P < .05) of proinflammatory cytokines on virus exposure compared with controls.<br><br>CONCLUSIONS: Nasal epithelium in LC exhibits persistent inflammatory states. SMURF1 upregulation potentially contributes to an exacerbated inflammatory state in nasal epithelium of patients with radiological abnormalities. This study demonstrates the importance of understanding these inflammatory profiles within a clinical context and emphasizes the need for further assessment and validation of SMURF1's role in LC.},
}
@article {pmid40482598,
year = {2025},
author = {Pelà, G and Frizzelli, A and Pisi, R and Calzetta, L and Marchese, A and Chetta, A and Aiello, M},
title = {Post-COVID-19 exaggerated exertional tachycardia: Relationship with pulmonary and cardiac sequelae.},
journal = {Heart &amp; lung : the journal of critical care},
volume = {73},
number = {},
pages = {228-235},
doi = {10.1016/j.hrtlng.2025.05.017},
pmid = {40482598},
issn = {1527-3288},
mesh = {Humans ; *COVID-19/complications/physiopathology ; Male ; Female ; Middle Aged ; *Tachycardia/physiopathology/etiology/diagnosis ; Heart Rate/physiology ; SARS-CoV-2 ; Aged ; Walk Test ; Exercise Test ; Adult ; },
abstract = {BACKGROUND: Long-COVID patients frequently complain of an Exaggerated Exertional Tachycardia (EET) and may represent a specific phenotype of post-COVID tachycardia syndrome. So far, no studies have investigated the factors contributing to EET.<br><br>OBJECTIVES: To determine the predictor factors of EET, seventy-nine Long-COVID-19 patients underwent comprehensive cardiologic and respiratory evaluations at follow-up visit after a median of 23 weeks from the acute phase of the disease.<br><br>METHODS: The heart rate (HR) response to exercise was assessed by the 6-minute walk test (6MWT), stratifying patients into two groups: EET and NET (normal exertional tachycardia).<br><br>RESULTS: The EET group was older, had higher body mass index and systolic blood pressure, with more comorbidities and lower resting HR, when compared to the NET group. The EET group also showed higher High-Resolution computed tomography scores and D-dimer levels during the acute phase compared to NET. At follow-up visit EET patients exhibited higher left ventricular mass and reduced systolic and diastolic function in both ventricles, as assessed by Doppler tissue echocardiography (myocardial S and E' waves). We found a significant reduction in lung diffusion capacity and in mean oxygen saturation during the 6MWT in EET patients compared to NET ones. Stepwise logistic regression analysis identified the mean oxygen saturation during the 6MWT as the predictor of abnormal HR response to exercise.<br><br>CONCLUSIONS: We found that the exaggerated heart response to exercise in Long COVID-19 patients is associated to an impaired pulmonary function at rest and is predicted by the oxygen exercise-induced desaturation.},
}
@article {pmid40481718,
year = {2025},
author = {Pérez-Cózar, F and Cal-Sabater, P and Rybakowska, P and Arribas-Rodríguez, E and Fiz-López, A and García-Blesa, A and Hernández, J and Gutiérrez, S and Tellería, P and Novoa, C and Rello, SR and De Prado, &#xc1; and Pérez, C and Sedano, R and Domínguez-Gil, M and Peñarrubia, MJ and Pieren, DKJ and Garrote, JA and Arranz, E and Eiros, JM and Tamayo, E and Orduña, A and van Els, CACM and Dueñas, C and Marañón, C and Bernardo, D and Cuesta-Sancho, S},
title = {High-Dimensional Immunophenotyping of Post-COVID-19 and Post-Influenza Patients Reveals Persistent and Specific Immune Signatures After Acute Respiratory Infection.},
journal = {Journal of medical virology},
volume = {97},
number = {6},
pages = {e70435},
pmid = {40481718},
issn = {1096-9071},
support = {//This study has been funded through Programa Estrat&#xe9;gico Instituto de Biomedicina y Gen&#xe9;tica Molecular (IBGM Junta de Castilla y Le&#xf3;n. Ref. CCVC8485), Junta de Castilla y Le&#xf3;n (Proyectos COVID 07.04.467B04.74011.0) and the European Commission-NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global: SGL21-03-026, SGL2021-03-038, COVID-19-117 and SGL2103015)./ ; },
mesh = {Humans ; *COVID-19/immunology ; Male ; Middle Aged ; Female ; Immunophenotyping/methods ; *Influenza, Human/immunology ; Adult ; Aged ; Leukocytes, Mononuclear/immunology ; SARS-CoV-2/immunology ; *Respiratory Tract Infections/immunology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long-term consequences of SARS-CoV-2 infection are unknown since recovered individuals can experience symptoms and latent viral reactivation for months. Indeed, acute post-infection sequelae have also been observed in other respiratory viral infections, including influenza. To characterize post-COVID-19 and post-influenza induced alterations to the cellular immunome, peripheral blood mononuclear cells (PBMCs) were obtained from patients 3 months after recovery from COVID-19 (n = 93) or influenza (n = 25), and from pre-pandemic healthy controls (n = 25). PBMCs were characterized using a 40-plex mass cytometry panel. Principal component analysis (PCA), classification models, and K-means clustering were subsequently applied. PCA identified distinct immune profiles between cohorts, with both post-COVID and post-flu patients displaying an altered chemokine receptor expression compared to pre-pandemic healthy controls. These alterations were more prominent in post-COVID patients since they exhibited highly increased expression of chemokine receptors CXCR3 and CCR6 by various lymphoid populations, while post-influenza patients mainly showed a decrease in CCR4 expression by naïve T cells, monocytes, and conventional dendritic cells. Classification models using immunophenotyping data confirm the three groups, while K-means clustering revealed two subgroups among post-COVID patients, with younger patients showing more pronounced immune alterations in the chemokine receptor profile, independently of long COVID symptoms. In conclusion, post-COVID and post-influenza patients exhibit distinct and unique persistent immune alterations. Understanding these altered immune profiles can guide targeted therapies for post-COVID syndrome and highlight differences in immune recovery from various respiratory infections.},
}
@article {pmid40481619,
year = {2025},
author = {Linton, J and Carmichael, J and Newlands, F and Puri, A and Fox-Smith, L and Pinto Pereira, SM and Coughtrey, A and Shafran, R and Stephenson, T},
title = {Pre-Pandemic Prevalence of Post COVID-19 Condition Symptoms in Adolescents.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {114},
number = {9},
pages = {2116-2123},
pmid = {40481619},
issn = {1651-2227},
support = {COV-LT-0022//UK Research and Innovation/ ; 183885//Beryl Alexander Charity PhD Studentship/ ; MR/Y009398/1//UK Medical Research Council Senior Non-clinical Fellowship/ ; //NIHR Great Ormond Street Hospital Biomedical Research Centre/ ; },
mesh = {Humans ; Adolescent ; *COVID-19/complications/epidemiology ; Prevalence ; Child ; Young Adult ; *Adolescent Health ; },
abstract = {AIM: The emergence of post COVID-19 condition (PCC) within adolescents has been characterised by a wide range of symptoms, raising concerns for young people's health and quality of life. However, many symptoms are non-specific and there is considerable variation in symptom reporting. It is essential to understand how rates of these symptoms compare to the pre-pandemic health of adolescents.<br><br>METHODS: A systematic search of academic literature and websites, using traditional and automated search systems, was undertaken to identify symptoms described in adolescents aged 10-19&#x2009;years in the 30&#x2009;years up to and including 2019. Studies were reviewed and symptom prevalence data extracted.<br><br>RESULTS: Twenty-five sources (n&#x2009;=&#x2009;483&#x2009;097 participants) met the inclusion criteria, including longitudinal and cross-sectional study designs. The description and prevalence of symptoms varied widely, but there was a high pre-pandemic median prevalence of cough (13.6%), headache (30.0%), and fatigue (20.5%). These high prevalences highlight a gap in understanding of pre-pandemic adolescent health and the need for comprehensive, serial symptom profiling.<br><br>CONCLUSION: These findings provide a baseline of adolescent symptomatology prior to the emergence of PCC and provide important context for interpreting ongoing COVID symptoms. Data on PCC in adolescents should consider pre-pandemic symptom prevalence.},
}
@article {pmid40481056,
year = {2025},
author = {Duong, KE and Lu, JY and Wang, S and Duong, TQ},
title = {Incidence and risk factors of new clinical disorders in patients with COVID-19 hyperinflammatory syndrome.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {19892},
pmid = {40481056},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Middle Aged ; Male ; Incidence ; Risk Factors ; Aged ; Adult ; SARS-CoV-2 ; Comorbidity ; *Inflammation/epidemiology ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Cardiovascular Diseases/epidemiology ; Asthma/epidemiology ; },
abstract = {This study investigated new incident clinical disorders in patients with COVID-19-related hyperinflammatory syndrome (cHIS) 3.5 years post infection. We analyzed 14,335 patients hospitalized with COVID-19 from March-2020 to July-2023. cHIS was defined based on a point system that included elevated body temperature, macrophage activation, hematological dysfunction, coagulopathy, and hepatic enzyme. Outcomes were newly diagnosed disorders of hypertension, diabetes, cardiovascular diseases, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and asthma post COVID-19. Cumulative incidences and hazard ratios were computed. Compared to non-cHIS patients, cHIS patients were older, fewer female, more Blacks, higher prevalence of pre-existing comorbidities. Patients with cHIS had higher risk of developing cardiovascular disease (HR = 1.24 [1.04,1.47] p < 0.05), CKD (1.24 [1.01, 1.53] p < 0.05), and obesity (1.61 [1.31,1.98], p < 0.001) but not hypertension, diabetes, COPD, and asthma. Cumulative incidence analysis showed that patients ≥ 50 years old showed markedly higher new incidences of individual new disorders compared to patients < 50 years old. COVID-19 related hyperinflammatory syndrome confers a significantly higher risk for developing new common clinical disorders. Identifying risks for developing new clinical disorders in patients with COVID-19 related hyperinflammatory syndrome may encourage diligent follow-up of high-risk individuals.},
}
@article {pmid40480667,
year = {2025},
author = {Nyaaba, GN and Torensma, M and Goldschmidt, MI and Nørredam, M and Moseholm, E and Appelman, B and Rostila, M and Tieleman, P and Biere-Rafi, S and Prins, M and Beune, E and Agyemang, C},
title = {Experiences of stigma and access to care among long COVID patients: a qualitative study in a multi-ethnic population in the Netherlands.},
journal = {BMJ open},
volume = {15},
number = {6},
pages = {e094487},
pmid = {40480667},
issn = {2044-6055},
mesh = {Humans ; Netherlands/epidemiology ; Female ; *COVID-19/ethnology/psychology/therapy ; Male ; *Health Services Accessibility ; *Social Stigma ; Qualitative Research ; Middle Aged ; Cross-Sectional Studies ; Adult ; Morocco/ethnology ; Turkey/ethnology ; *Ethnicity/psychology ; SARS-CoV-2 ; Aged ; },
abstract = {OBJECTIVE: This study explored the experience of stigma and access to healthcare by persons with long COVID from the majority Dutch and two ethnic minority populations (Turkish and Moroccan) living in the Netherlands.<br><br>DESIGN: This was a cross-sectional qualitative study that employed inductive and deductive thematic approaches to data analysis using MAXQDA.<br><br>SETTING AND PARTICIPANTS: Between October 2022 and January 2023, 23 semi-structured interviews were conducted with participants of Dutch, Moroccan and Turkish ethnic origins with long COVID living in the Netherlands. Participants were men and women aged 30 years and above.<br><br>RESULTS: Guided by the concepts of stigma and candidacy, the findings are structured according to the broader themes of stigma and access to care. The findings show that people with long COVID suffer self and public stigma resulting from the debilitating illness and symptoms. Especially among Turkish and Moroccan ethnic minority participants, strong filial obligations and gendered expectations of responsibility and support within their communities further worsen self-stigma. This experience of stigma persisted within healthcare where lack of information and appropriate care pathways led to feelings of frustration and abandonment, especially for participants with pre-existing health conditions which further complicate candidacy. Under the access to healthcare theme, the findings show multiple challenges in accessing healthcare for long COVID due to several multifaceted factors related to the various stages of candidacy which impacted access to care. Particularly for Turkish and Moroccan ethnic minority participants, additional challenges resulting from limited access to information, pre-existing structural challenges and experience of stereotyping based on ethnicity or assumed migrant identity by health professionals further complicate access to health information and long COVID care.<br><br>CONCLUSIONS: The findings call for urgent attention and research to identify and coordinate healthcare for long COVID. There is also a need for accessible, informative and tailored support systems to facilitate patients' access to information and care pathways for long COVID. Providing tailored information and support, addressing the various barriers that hinder optimal operating conditions in healthcare and leveraging on social networks is crucial for addressing stigma and facilitating candidacy for persons with long COVID towards improving access to care.},
}
@article {pmid40478845,
year = {2025},
author = {Kim, J and Lee, S and Weir, P},
title = {Long-COVID is associated with increased absenteeism from work.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0325280},
pmid = {40478845},
issn = {1932-6203},
mesh = {Humans ; Female ; *COVID-19/epidemiology/economics ; Adult ; Male ; Middle Aged ; *Absenteeism ; SARS-CoV-2/isolation &amp; purification ; Adolescent ; Young Adult ; Aged ; },
abstract = {Long-COVID, defined as COVID-19 symptoms persisting for more than 3 months, may lead to persistent health issues requiring extensive medical care. Despite its long-term health impact, the economic impact of long-COVID remains understudied. This study examined whether individuals with long-COVID had more missed workdays compared to those without long-COVID. Adults (≥18 years old) with full-time jobs were identified from the 2022 Full-Year Population Characteristics file of the Medical Expenditure Panel Survey (MEPS). A weighted two-part model was used to identify factors associated with missed workdays due to illness. The total population analyzed included 131,685,516 adults (unweighted n = 8,210), with an average (SD) age of 43 (14) years. Among them, 46% were female and 62% were non-Hispanic White. Approximately 7% of the population experienced long-COVID. Individuals with long-COVID reported an average of 8 days missed from work (SD: 12 days), while those without long-COVID reported an average of 4 days missed (SD: 9 days). The two-part model revealed that individuals with long-COVID had 2.54 more missed workdays compared to those without long-COVID (p < 0.01), after controlling for relevant variables. These results underscore significant productivity losses associated with long-COVID, highlighting the need for policymakers and employers to implement effective strategies to address this condition.},
}
@article {pmid40478517,
year = {2025},
author = {Schwartz, CE and Borowiec, K and Rapkin, BD},
title = {Long-COVID symptom burden and the experience of adversity: the importance of response-shift effects over 3 years of the pandemic.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {34},
number = {8},
pages = {2233-2257},
pmid = {40478517},
issn = {1573-2649},
mesh = {Humans ; *COVID-19/psychology/epidemiology ; Male ; Longitudinal Studies ; Female ; Middle Aged ; Adult ; *Quality of Life/psychology ; SARS-CoV-2 ; Social Support ; *Cost of Illness ; Pandemics ; Aged ; Symptom Burden ; },
abstract = {BACKGROUND/OBJECTIVES: Long COVID is a long-term legacy of the global pandemic. This study aimed to illuminate how Long COVID impacts individuals, and how response-shift effects influence Long COVID's impact. Methodologically, it expands the application of longitudinal statistical methods to test a more dynamic investigation of psychosocial factors in health over time.<br><br>METHODS: This quasi-experimental longitudinal cohort study collected data up to four times over 3&#xa0;years of the COVID pandemic (May 2020 to April 2023). This study focused on 1151 participants divided into four Long-COVID Symptom Burden groups (Never Had COVID; Low, Medium, and High Long-COVID Symptom Burden). It examined COVID-specific outcomes: General Hardship, Healthcare Hardship, Worry, and Social Support. The Quality of Life Appraisal Profilev2-Short Form assessed cognitive-appraisal processes. Direct and moderated response-shift effects were tested using longitudinal mixed models that examined main effects and interactions of individuals' changes in cognitive-appraisal processes from their usual, over time, and by group over time, after adjusting for sociodemographic covariates and individual's usual appraisal processes, and considering the impact of multiple comparisons.<br><br>RESULTS: Notable response-shift effects were revealed on all four COVID-specific outcomes, reflecting both direct and moderated response-shift effects. The experience of COVID-specific adversity was related to various appraisal processes but the nature of the relationship often varied by Long-COVID symptom burden. The appraisal processes that were most salient included patterns of emphasis related to getting used to and handling demands or recent changes, problem-solving goals, and comparing oneself to similar others. Individuals in the high Long-COVID Symptom-Burden Group were particularly highlighted in response-shift effects. The broad conclusions of both raw and multiplicity-adjusted results were similar. That is, there were notable reprioritization and reconceptualization response-shift effects for all outcomes, and notable but fewer recalibration response-shift effects.<br><br>CONCLUSIONS: Response-shift effects, measured via the direct assessment of cognitive-appraisal processes, were prominent in dealing with the COVID pandemic. The present study documented that COVID-specific adversity can be attenuated or exacerbated depending on individuals' patterns of emphasis, goals, and standards of comparison. The study's utilization of data collected at four time points over 3 years of the global pandemic provided a more comprehensive and far-reaching evaluation of response shift than earlier work. The theory-driven analytic methodology developed in the present work facilitated a more nuanced description of direct and moderated response-shift effects.},
}
@article {pmid40476637,
year = {2025},
author = {Rahmati, M and Udeh, R and Kang, J and Dolja-Gore, X and McEvoy, M and Kazemi, A and Soysal, P and Smith, L and Kenna, T and Fond, G and Boussat, B and Nguyen, DC and Do, H and Tran, BX and Veronese, N and Yon, DK and Boyer, L},
title = {Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of Symptoms 3 Years Post-SARS-CoV-2 Infection.},
journal = {Journal of medical virology},
volume = {97},
number = {6},
pages = {e70429},
pmid = {40476637},
issn = {1096-9071},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue/epidemiology ; Dyspnea/epidemiology ; SARS-CoV-2 ; Prevalence ; Sleep Wake Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; Survivors ; },
abstract = {The symptoms of long COVID are well-documented. However, the long-term effects beyond 2 years remain poorly understood due to a lack of data. This systematic review and meta-analysis examined the prevalence of persistent symptoms in COVID-19 survivors 3 years following initial SARS-CoV-2 infection. PubMed, MEDLINE (Ovid), CENTRAL, Web of Science, Scopus, and Embase were searched from inception of the databases up to July 20, 2024, by two independent researchers for articles reporting on the prevalence of persistent symptoms 3 years' post-infection of people who survived COVID-19 infection. We employed a random-effect model for the pooled analysis, and the meta-analytical effect size was prevalence for the applicable end-points, I[2] statistics, and quality assessment of included studies using the Newcastle-Ottawa Scale. Eleven articles were included after the literature search yielded 223 potentially relevant articles. We found that among patients with long COVID, fatigue, sleep disturbances, and dyspnea were the most common symptoms. Pooled analysis showed that the proportion of individuals experiencing at least one persistent symptom 3 years post-COVID-19 is 20% (95% confidence interval [CI]: 8-43). The prevalence of persistent symptoms was dyspnea (12%; 95% CI: 10-15), fatigue (11%; 95% CI: 6-20), insomnia (11%; 95% CI: 2-37), loss of smell (7%; 95% CI: 5-8), loss of taste (7%; 95% CI: 3-16), and anxiety (6%; 95% CI: 1-32). Prevalence of other findings include impaired diffusion capacity (42%; 95% CI: 34-50) and impaired forced expiratory volume in 1 s (10%; 95% CI: 8-12). Our findings confirm the persistence of unresolved symptoms 3 years post-COVID-19 infection, with implications for future research, healthcare policy, and patient care.},
}
@article {pmid40475767,
year = {2025},
author = {Wolday, D and Gebrehiwot, AG and Le Minh, AN and Rameto, MA and Abdella, S and Gebreegziabxier, A and Amogne, W and Rinke de Wit, TF and Hailu, M and Tollera, G and Tasew, G and Tessema, M and Miller, M and Gillgrass, A and Bowdish, DME and Kaushic, C and Verschoor, CP},
title = {Distinct proteomic signatures in Ethiopians predict acute and long-term sequelae of COVID-19.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1575135},
pmid = {40475767},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/blood/immunology/complications ; Male ; Female ; *SARS-CoV-2 ; Middle Aged ; Adult ; Proteomics ; Biomarkers/blood ; Aged ; *Proteome ; East African People ; },
abstract = {INTRODUCTION: Little is known about the acute and long-term sequelae of COVID-19 and its pathophysiology in African patients, who are known to have a distinct immunological profile compared to Caucasian populations. Here, we established protein signatures to define severe outcomes of acute COVID-19 and determined whether unique protein signatures during the first week of acute illness predict the risk of post-acute sequelae of COVID-19 (Long COVID) in a low-income country (LIC) setting.<br><br>METHOD: Using the Olink inflammatory panel, we measured the abundance of 92 proteins in the plasma of COVID-19 patients (n=55) and non-COVID-19 individuals (n=23). We investigated distinct inflammatory protein signatures in acute severe COVID-19 individuals (n=22) compared to asymptomatic or mild/moderate COVID-19 cases (n=33), and non-COVID-19 controls.<br><br>RESULTS: Levels of SLAMF1, CCL25, IL2RB, IL10RA, IL15RA, IL18 and CST5 were significantly upregulated in patients with critical COVID-19 illness compared to individuals negative for COVID-19. The cohort was followed for an average of 20 months, and 23 individuals developed Long COVID, based on the WHO's case definition, while 32 COVID-19 patients recovered fully. Whereas upregulated levels of SLAMF1, TNF, TSLP, IL15RA, IL18, ADA, CXCL9, CXCL10, IL17C, and NT3 at the acute phase of the illness were associated with increased Long COVID risk, upregulated TRANCE was associated with a reduced risk of developing Long COVID. Protein levels of SLAMF1, IL15RA, and IL18 associated with critical illness during the acute phase of COVID-19 also predicted Long COVID risk.<br><br>DISCUSSION: Patients with severe COVID-19 and Long COVID outcomes exhibited distinct proteomic signatures. Unravelling the pathophysiology of severe acute COVID-19 and Long COVID before its advent may contribute to designing novel interventions for diagnosing, treating, and monitoring of SARS-CoV-2 infection and its associated acute and long-term consequences.},
}
@article {pmid40475143,
year = {2025},
author = {Hu, C and Son, J and McAlpine, L and Walker, EL and Dahl, M and Song, E and Ferreira Brito, S and Kavak, K and Onomichi, K and Bar-Or, A and Perrone, C and Riley, CS and Weinstock Guttman, B and De Jager, PL and Longbrake, EE and Xia, Z},
title = {Long COVID in people with multiple sclerosis and related disorders: a multicenter cross-sectional study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40475143},
support = {R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; },
abstract = {BACKGROUND: Managing long COVID in people with multiple sclerosis and related disorders (pwMSRD) is complex due to overlapping symptoms. To address evidence gaps, we evaluated long COVID susceptibility in pwMSRD versus controls and its associations with multi-domain function and disability.<br><br>METHODS: In this multicenter cross-sectional study, participants completed a survey covering 71 post-infection symptoms, distinguishing new-onset from worsening symptoms. We defined long COVID using the 2024 NASEM criteria. Logistic regression assessed long COVID odds. Linear and Poisson regression evaluated associations with function and disability.<br><br>RESULTS: 969 pwMSRD (82.5% female, mean age 51.8 years, 63.5% infected) and 1,003 controls (79.4% female, mean age 45.2 years, 61.2% infected) were included. PwMSRD had higher odds of long COVID (aOR=1.6 [1.2-2.1]), with a stronger association when restricting to worsening symptoms (aOR=2.3 [1.7-3.1]). Having long COVID was associated with worse physical function, cognition, and depression in both groups. PwMSRD with long COVID experienced greater physical function declines and more depression severity exacerbation than controls, and had faster disability progression compared to those without long COVID.<br><br>CONCLUSION: PwMSRD show increased susceptibility to long COVID, primarily driven by worsening symptoms. Long COVID contributes to more functional decline and disability worsening. Recognizing and managing long COVID is essential in pwMSRD.},
}
@article {pmid40474772,
year = {2025},
author = {Gupta, G and Buonsenso, D and Wood, J and Mohandas, S and Warburton, D},
title = {Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.},
journal = {Comprehensive Physiology},
volume = {15},
number = {3},
pages = {e70019},
doi = {10.1002/cph4.70019},
pmid = {40474772},
issn = {2040-4603},
mesh = {Humans ; *COVID-19/immunology/complications/virology/physiopathology ; *SARS-CoV-2/physiology ; *Multiple Organ Failure/immunology/virology/etiology ; Post-Acute COVID-19 Syndrome ; Animals ; },
abstract = {Long Covid is a post-viral syndrome characterized by persistent symptoms targeting multiple organ systems after initial SARS-CoV-2 infection. Current literature suggests that the mechanisms causing Long Covid involve viral persistence, immune dysregulation, systemic inflammation, endothelial dysfunction, and metabolic disturbances. By forming reservoirs in the tissues of various organs, SARS-CoV-2 may evade immunological clearances while triggering immune responses and contributing to chronic symptoms through cytokine imbalances, T-cell exhaustion, and systemic inflammation. These symptoms parallel other post-viral syndromes such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), suggesting similar mechanisms of pathology. The coronavirus has also been linked to neuroinflammation and endothelial dysfunction causing cognitive symptoms and cardiovascular complications. Furthermore, its ability to lower energy production links it to post-exertion malaise (PEM) and muscle pain. These symptoms may result from iron dysregulation and persistent oxidative stress due to Covid-impaired mitochondrial function. This review synthesizes current data on the mechanisms that drive Long Covid pathogenesis and explores potential therapeutic strategies to mitigate viral persistence, immune dysfunction, and metabolic disturbances. It is critical to understand these interactions to develop targeted interventions that address the long-term sequelae of SARS-CoV-2 infection and improve patient outcomes.},
}
@article {pmid40473290,
year = {2025},
author = {Jamieson, A and Saikhan, LA and Raman, B and Alghamdi, L and Cheetham, NJ and Conde, P and Dobson, R and Fernández-Sanlés, A and Folarin, A and Goudswaard, LJ and Hamill Howes, L and Jones, S and Neubauer, S and Orini, M and Pierce, I and Ranjan, Y and Rapala, A and Smith, SM and Sudre, C and Thompson, EJ and Wild, J and Williams, D and Wong, A and Steves, CJ and Timpson, N and Chaturvedi, N and Hughes, A},
title = {Cohort profile: characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19 - providing the evidence base for health care services (CONVALESCENCE) in the UK.},
journal = {BMJ open},
volume = {15},
number = {6},
pages = {e094760},
pmid = {40473290},
issn = {2044-6055},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/physiopathology/therapy ; Male ; Female ; United Kingdom/epidemiology ; Case-Control Studies ; Adult ; Middle Aged ; SARS-CoV-2 ; Longitudinal Studies ; *Convalescence ; Aged ; Post-Acute COVID-19 Syndrome ; Adolescent ; Child ; },
abstract = {PURPOSE: The pathogenesis of the long-lasting symptoms which can follow an infection with the SARS-CoV-2 virus ('long covid') is not fully understood. The 'COroNaVirus post-Acute Long-term EffectS: Constructing an evidENCE base' (CONVALESCENCE) study was established as part of the Longitudinal Health and Wellbeing COVID-19 UK National Core Study. We performed a deep phenotyping case-control study nested within two cohorts (the Avon Longitudinal Study of Parents and Children and TwinsUK) as part of CONVALESCENCE.<br><br>PARTICIPANTS: From September 2021 to May 2023, 349 participants attended the CONVALESCENCE deep phenotyping clinic at University College London. Four categories of participants were recruited: cases of long covid (long covid(+)/SARS-CoV-2(+)), alongside three control groups: those with neither long covid symptoms nor evidence of prior COVID-19 (long covid(-)/SARS-CoV-2(-); control group 1), those who self-reported COVID-19 and had evidence of SARS-CoV-2 infection, but did not report long covid (long covid(-)/SARS-CoV-2(+); control group 2) and those who self-reported persistent symptoms attributable to COVID-19 but no evidence of SARS-CoV-2 infection (long covid(+)/SARS-CoV-2(-); control group 3). Remote wearable measurements were performed up until February 2024.<br><br>FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the CONVALESCENCE cohort. Of the 349 participants, 141 (53&#xb1;15 years old; 21 (15%) men) were cases, 89 (55&#xb1;16 years old; 11 (12%) men) were in control group 1, 75 (49&#xb1;15 years old; 25 (33%) men) were in control group 2 and 44 (55&#xb1;16 years old; 9 (21%) men) were in control group 3.<br><br>FUTURE PLANS: The study aims to use a multiorgan score calculated as the cumulative total for each of nine domains (ie, lung, vascular, heart, kidney, brain, autonomic function, muscle strength, exercise capacity and physical performance). The availability of data preceding acute COVID-19 infection in cohorts may help identify the consequences of infection independent of pre-existing subclinical disease and also provide evidence of determinants that influence the development of long covid.},
}
@article {pmid40472281,
year = {2025},
author = {Wolock, CJ and Jacob, S and Bennett, JC and Elias-Warren, A and O'Hanlon, J and Kenny, A and Jewell, NP and Rotnitzky, A and Cole, SR and Weil, AA and Chu, HY and Carone, M},
title = {Investigating Symptom Duration Using Current Status Data: A Case Study of Postacute COVID-19 Syndrome.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {36},
number = {5},
pages = {650-659},
pmid = {40472281},
issn = {1531-5487},
support = {R01 HL137808/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; Post-Acute COVID-19 Syndrome ; Time Factors ; Female ; Male ; SARS-CoV-2 ; Adult ; Middle Aged ; Washington/epidemiology ; },
abstract = {BACKGROUND: For infectious diseases, characterizing symptom duration is of clinical and public health importance. Symptom duration may be assessed by surveying infected individuals and querying symptom status at the time of survey response. For example, in a severe acute respiratory syndrome coronavirus 2 testing program at the University of Washington, participants were surveyed at least 28 days after testing positive and asked to report current symptom status. This study design yielded current status data: outcome measurements for each respondent consisted only of the time of survey response and a binary indicator of whether symptoms had resolved by that time. Such study design benefits from limited risk of recall bias, but analyzing the resulting data necessitates tailored statistical tools.<br><br>METHODS: We review methods for current status data and describe a novel application of modern nonparametric techniques to this setting. The proposed approach is valid under weaker assumptions compared with existing methods, allows the use of flexible machine learning tools, and handles potential survey nonresponse. Our method relies on the assumption that the survey response time is conditionally independent of symptom resolution time within strata of measured covariates, and we propose an approach to assess the sensitivity of results to deviations from conditional independence.<br><br>RESULTS: From the university study, we estimate that 19% of participants experienced ongoing symptoms 30 days after testing positive, decreasing to 7% at 90 days. We found the estimates to be more sensitive to violations of the conditional independence assumption at 30 days compared with 90 days. Female sex, fatigue during acute infection, and higher viral load were associated with slower symptom resolution.<br><br>CONCLUSION: The proposed method and accompanying sensitivity analysis procedure provide tools for investigators faced with current status data.},
}
@article {pmid40470597,
year = {2025},
author = {Resta, E and Noviello, C and Peter, P and Graziano, G and Dalena, V and Caputi, A and Castellana, G and Riformato, G and Tafuri, S and Pierucci, P},
title = {Respiratory post COVID sequelae: the role of pulmonary function impairment, fatigue and obesity in dyspnea and the impact of SPA rehabilitation.},
journal = {Expert review of respiratory medicine},
volume = {19},
number = {9},
pages = {1017-1026},
doi = {10.1080/17476348.2025.2516801},
pmid = {40470597},
issn = {1747-6356},
mesh = {Humans ; *Dyspnea/physiopathology/etiology/rehabilitation ; Male ; Female ; *COVID-19/complications/physiopathology/rehabilitation ; Middle Aged ; *Fatigue/physiopathology/etiology/epidemiology ; *Obesity/epidemiology/physiopathology/complications ; Aged ; Respiratory Function Tests ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; },
abstract = {BACKGROUND: Respiratory COVID-19 post-acute sequelae (PASC) may persist for extended periods following recovery.<br><br>METHODS: Patients with PASC who were referred for Salus Per Aquam (SPA) therapy were enrolled in the study.<br><br>AIM: To categorize patients based on the presence of dyspnea and fatigue, with a specific focus on obesity, chronic respiratory conditions, and predictors of rehabilitation outcomes.<br><br>RESULTS: From July-November 2021, 327 consecutive patients were enrolled at the spa center. Among these, 31% had been previously hospitalized, 5% had required noninvasive or invasive mechanical ventilation. Approximately one-third of the cohort underwent DLCO testing, which was abnormal in 56.3% of cases. Patients with impaired DLCO had significantly higher dyspnea rates compared to those with normal DLCO (88.9% vs. 64.3%, p&#x2009;<&#x2009;0.0001). Dyspneic patients were more likely to have one or more comorbidities (p&#x2009;<&#x2009;0.001), be obese (p&#x2009;=&#x2009;0.005), and have a history of chronic respiratory disease (p =&#x2009;0.0009). Patients reporting fatigue also had higher rates of dyspnea (91.2% vs. 61.5%, p&#x2009;<&#x2009;0.0001), were more frequently obese (p&#x2009;=&#x2009;0.03), had more comorbidities (p&#x2009;=&#x2009;0.02), and had a greater history of hospitalization (p&#x2009;=&#x2009;0.02). No improvement in dyspnea/fatigue was observed post-SPA treatment among patients with DLCO impairment and obese. However, patients with chronic respiratory conditions reported benefit.<br><br>CONCLUSIONS: Dyspnea in PASC is complex and multifactorial. The findings suggest that SPA rehabilitation may be particularly beneficial for alleviating fatigue and enhancing overall well-being in selected subgroups of patients with PASC.},
}
@article {pmid40470564,
year = {2025},
author = {Iannuccelli, C and Favretti, M and Dolcini, G and Di Carlo, M and Pellegrino, G and Bazzichi, L and Atzeni, F and Lucini, D and Varassi, G and Leoni, MLG and Fornasari, DMM and Conti, F and Salaffi, F and Sarzi-Puttini, P and Di Franco, M},
title = {Fibromyalgia: one year in review 2025.},
journal = {Clinical and experimental rheumatology},
volume = {43},
number = {6},
pages = {957-969},
doi = {10.55563/clinexprheumatol/buhd2z},
pmid = {40470564},
issn = {0392-856X},
mesh = {Humans ; *Fibromyalgia/therapy/physiopathology/diagnosis/epidemiology/psychology ; Quality of Life ; COVID-19/epidemiology ; },
abstract = {Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain, high prevalence, and a significant impact on quality of life. Despite extensive research, its pathogenesis and treatment remain only partially understood, driving continued investigation throughout 2024. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system has been linked to chronic stress responses and neuroinflammation, with neuroimaging and preclinical studies confirming altered pain and stress processing. Low-grade inflammation and metabolic disturbances, including cytokine imbalance and increased adipose tissue infiltration, further exacerbate symptoms. Alterations in the gut microbiota contribute to immune and emotional dysregulation. MRI studies continue to reveal brain changes that differentiate FM from other chronic pain disorders. Multi-omics approaches, including transcriptomic and metabolomic analyses, show promise as diagnostic biomarkers. Mitochondrial dysfunction also emerges as a key factor, since impaired energy metabolism seems to correlate with symptom severity. From a clinical perspective, recent studies have explored under-recognised aspects of FM, such as sexual and cognitive dysfunction, the role of gender, environmental exposures, and the disease's impact on relationships and family life. The differential diagnosis of FM and long COVID has ignited discussion about potential shared mechanisms. Conversely, residual pain in inflammatory diseases remains insufficiently addressed. Therapeutically, non-pharmacological strategies, particularly physical activity and psychosocial interventions, remain fundamental. Emerging areas such as non-invasive neuromodulation, psychedelic therapies, and the integration of technologies like virtual reality and artificial intelligence are opening new frontiers in treatment, patient care, and research. These advances underscore the multifactorial nature of FM and the need for personalised, interdisciplinary approaches.},
}
@article {pmid40470173,
year = {2025},
author = {Loli, A and Müller, JVC and de Azevedo, ES and Martins, RHG},
title = {Symptoms and Otorhinolaryngological Sequalae in Long Covid.},
journal = {International archives of otorhinolaryngology},
volume = {29},
number = {2},
pages = {1-6},
pmid = {40470173},
issn = {1809-9777},
abstract = {INTRODUCTION: After the pandemic caused by the coronavirus, many patients have presented remaining otorhinolaryngological symptoms, but most of them are unknown to health professionals.<br><br>OBJECTIVES: To characterize otorhinolaryngological symptoms and sequelae in hospitalized patients for Covid-19.<br><br>METHODS: We made a recall to patients hospitalized between April 2020 and April 2022 due to Covid-19. Demographic data, initial and remaining symptoms, days of hospitalization, intubation and/or tracheostomy, and vaccination data were collected.<br><br>RESULTS: 845 patients were hospitalized, 441 died, 404 patients were contacted by telephone, but only 109 responded to the questionnaire about initial and remaining otorhinolaryngological symptoms after 1.5 to 2 years of illness, 59 men and 50 women, with an average age of 58.61 years (20 to 94). Two study groups were composed: G 1 (n- 44; with remaining symptoms) and G 2 (n- 65; without remaining symptoms). 81% of patients in G1 and 67% of patients in G2 had been hospitalized for up to 20 days. Intubation occurred in 17 patients (G1-7; G2-10). Seven patients underwent tracheostomy. The most prevalent initial and remaining otorhinolaryngological symptoms, respectively, were dyspnea (68.8%; 14.6%), cough (65.1%; 11.92%), nasal obstruction (47.7%; 5.58%), smell dysfunction (44%; 11%), taste dysfunction (42%; 4.58%). Vaccination was reported by 54 patients (G1-21; G2-34).<br><br>CONCLUSIONS: Otorhinolaryngological symptoms were common in patients hospitalized for Covid-19, especially dyspnea, cough, nasal obstruction, smell, and taste dysfunction. Although there was a favorable long-term evolution, 40% of patients maintained permanent symptoms, such as smell and taste dysfunction and dizziness, unrelated to the vaccine doses.},
}
@article {pmid40470163,
year = {2025},
author = {Pike Welch, HL and Guest, G and Garba, H and Carrillo, GA and Damman, AM and Kibbe, WA},
title = {A community-engaged approach to developing common data elements: a case study from the RADx-UP Long COVID common data elements Task Force.},
journal = {JAMIA open},
volume = {8},
number = {3},
pages = {ooaf046},
pmid = {40470163},
issn = {2574-2531},
support = {U24 MD016258/MD/NIMHD NIH HHS/United States ; },
abstract = {OBJECTIVES: In response to requests from several Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) community-engaged research projects to include Long COVID common data elements (CDEs) in the existing RADx-UP CDEs, the RADx-UP Coordination and Data Collection Center (CDCC) leadership formed the Long COVID CDEs Task Force.<br><br>MATERIALS AND METHODS: The Task Force, composed mainly of community partners and RADx-UP project members, participated in various activities to evaluate the Long COVID CDEs fit for purpose from the Researching COVID to Enhance Recovery (RECOVER) program for RADx-UP use.<br><br>RESULTS&#xa0;AND DISCUSSION: The Task Force's efforts led to a compilation of lessons learned and the creation of a novel set of 28 CDEs that are appropriate for community-engaged research in Long COVID.<br><br>CONCLUSION: Utilization of standardized CDEs does not always work for the communities involved in the research, but creation of a community-involved task force can lead to a meaningful, rich set of CDEs.},
}
@article {pmid40470145,
year = {2025},
author = {Gallo González, V and López-Padilla, D and de Miguel Díez, J and Suárez Escudero, S and Ojeda Castillejo, E and Ji, Z and Puente Maestu, L},
title = {Long COVID-19 and longer sick leave: longitudinal study of economically active patients.},
journal = {ERJ open research},
volume = {11},
number = {3},
pages = {},
pmid = {40470145},
issn = {2312-0541},
abstract = {INTRODUCTION: Sick leave was one of the numerous consequences of the COVID-19 pandemic. Given the relevance of occupational status for any individual, the aim of the study was to evaluate the impact of persistent symptoms after active infection and determine factors associated with longer sick leaves (LSLs).<br><br>METHODS: This observational study focused on economically active patients attending a post-COVID outpatient clinic for persistence of symptoms or radiological alterations after active infection. The LSL temporal cut-off point was defined by the third tertile of total leave days. Median leave time was compared with the optimal sick leave time for any other viral pneumonia, estimated by the local Ministry of Employment. To determine factors associated with LSL, multivariate models were ultilised.<br><br>RESULTS: A total of 248 patients were included. The median sick leave time for the entire population was 53&#x2005;days (interquartile range (IQR) 37.0-126.5), global sum of 30&#x2009;169&#x2005;days; the median optimal sick leave time was 21.9&#x2005;days (IQR 19.7-25.9) (p<0.05). The third tertile cut-off point for LSL was 83&#x2005;days and multivariate analysis showed a significant association with dyspnoea (OR 3.26, 95% CI 1.59-6.70, p=0.0001), while physical exercise of at least 10&#x2005;min&#xb7;day[-1] was significantly associated with shorter sick leave durations (OR 0.45, 95% CI 0.20-0.98, p=0.04).<br><br>DISCUSSION: COVID-19 sick leave was considerably longer than that stipulated for nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia. Long-COVID syndrome, especially dyspnoea, seems to be a very present factor in these patients' inability to work.},
}
@article {pmid40469928,
year = {2025},
author = {Honchar, O and Ashcheulova, T and Bobeiko, A and Blazhko, V and Khodosh, E and Matiash, N and Syrota, V},
title = {12-Month trajectories of physical and mental symptom scores after COVID-19 hospitalization and their role in predicting "very long" COVID.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1568291},
pmid = {40469928},
issn = {2673-6861},
abstract = {BACKGROUND: Long COVID syndrome (LCS) represents a significant global health challenge due to its wide-ranging physical and cognitive symptoms that persist beyond 12 months in a substantial proportion of individuals recovering from SARS-CoV-2 infection. Developing tools for predicting long-term LCS persistence can improve patient management and resource allocation.<br><br>OBJECTIVE: To evaluate the natural dynamics of symptoms over 12 months following hospitalization for COVID-19 and to establish the utility of survey-based symptoms assessment for predicting LCS at one year.<br><br>METHODS: This prospective observational study included 166 hospitalized COVID-19 survivors who were evaluated pre-discharge and followed up at 1, 3, and 12 months. Assessments included surveys including physical and mental symptom scales (e.g., EFTER-COVID, SBQ-LC, PCFS, MRC Dyspnea, CAT, CCQ, and HADS) and machine learning modeling to predict LCS persistence at 12 months.<br><br>RESULTS: LCS symptoms were reported by 76% of patients at three months and 43% at 12 months. Physical symptom scores, particularly EFTER-COVID and PCFS, consistently differentiated LCS and LCS-free cohorts. CAT outperformed other respiratory scales in its discriminatory ability, while HADS subscales showed limited predictive value. Younger patients (<40 years) demonstrated faster recovery, whereas older patients (>60 years) exhibited persistent symptoms across respiratory and cognitive domains. A machine learning model combining EFTER-COVID, SBQ-LC, CAT, and MRC Dyspnea scores achieved 91% predictive accuracy for LCS persistence at 12 months.<br><br>CONCLUSION: Comprehensive survey-based symptoms assessment at three months post-discharge provides a practical and cost-effective tool for prediction of the long COVID persistence at 12 months, supporting targeted rehabilitation strategies.},
}
@article {pmid40469004,
year = {2025},
author = {Faux-Nightingale, A and Saunders, B and Burton, C and Chew-Graham, CA and Somayajula, G and Twohig, H and Welsh, V},
title = {Perceptions and Significance of Long Covid Diagnoses From the Perspectives of Children and Young People With Long Covid, Their Parents and Professionals.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70318},
pmid = {40469004},
issn = {1369-7625},
support = {//This study presents independent research funded by the NIHR School for Primary Care Research (Grant Reference Number 517) and the NIHR West Midlands Clinical Research Network. C.B. is funded by a National Institute for Health Research (NIHR) Clinical Lectureship. V.W. is part-funded by WM ARC./ ; },
mesh = {Humans ; Child ; *COVID-19/diagnosis/psychology ; Adolescent ; Female ; *Parents/psychology ; Focus Groups ; Interviews as Topic ; Male ; Qualitative Research ; SARS-CoV-2 ; *Health Personnel/psychology ; },
abstract = {INTRODUCTION: Long Covid, the patient-preferred term, describes symptoms persisting after an acute Covid-19 infection. Understanding the importance and meaning of a Long Covid diagnosis to children and young people (CYP), their families and professionals associated with their care can give insight into the way that these diagnoses are used across these groups to support care and needs of the patient. This study explores the meaning and importance of a Long Covid diagnosis from the perspectives of CYP with Long Covid, their parents and relevant professionals.<br><br>METHODS: CYP and their parents or carers were invited to interview following participation in an initial cohort study. Professionals with experience working with CYP with Long Covid were invited to participate in a focus group. Interviews were carried out with four CYP with Long Covid (all female, aged 10-17 years); parents were present at three interviews. Seven professionals with experience in the care of CYP or Long Covid participated in one of two focus groups. Data were analysed thematically using constant comparison techniques.<br><br>RESULTS: The three main themes presented are as follows: the importance of receiving a diagnosis, diagnosis facilitates access to support and perspectives of discordance between family and professionals. The diagnosis of Long Covid has different meanings and significance for parents and professionals. Families described the diagnosis as a legitimisation of their experiences and a way to access support, but professionals questioned some of the ways families use the diagnosis, focusing instead on appropriate treatment according to CYP's needs.<br><br>CONCLUSION: For families, Long Covid diagnoses are important for validating and legitimising symptoms, removing uncertainty, and supporting access and participation, particularly in school. While these uses differ from those of professionals, understanding the importance of a Long Covid diagnosis to families may ensure effective communication, negotiation of an acceptable management plan, and ongoing support for this group.<br><br>Patients and the public contributed throughout this project and had input on the study design, topic guides, and dissemination of findings.},
}
@article {pmid40467399,
year = {2025},
author = {Chia-Ying, L and Hsin-Sui, H and Chun-Hsing, L},
title = {Long COVID Clinical Features in Northern Taiwan: Insights from a Single Medical Center Study.},
journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi},
volume = {58},
number = {6},
pages = {678-687},
doi = {10.1016/j.jmii.2025.05.006},
pmid = {40467399},
issn = {1995-9133},
mesh = {Humans ; Taiwan/epidemiology ; Male ; *COVID-19/epidemiology/complications ; Female ; Aged ; Quality of Life ; Middle Aged ; Prospective Studies ; Hospitalization/statistics &amp; numerical data ; SARS-CoV-2 ; Adult ; Risk Factors ; Surveys and Questionnaires ; Aged, 80 and over ; Telemedicine ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID, encompasses persistent symptoms following acute COVID-19, impacting quality of life. This study delineates the epidemiology, clinical presentation, and quality of life effects of long COVID in Northern Taiwan using data from the 2021 COVID-19 home quarantine telemedicine care system.<br><br>METHODS: A prospective cohort of 625 PCR-confirmed COVID-19 patients, diagnosed between April and October 2021, was monitored for 3-6 months post-recovery. We assessed persistent symptoms, quality of life via the EQ-5D questionnaire, and risk factors including age, sex, vaccination status, household clusters, and hospitalization.<br><br>RESULTS: Among participants, 22&#xa0;% reported malaise, 14&#xa0;% dyspnea, and 7&#xa0;% cough as persistent symptoms. Older age (&#x2265;65 years) and hospitalization were associated with greater quality of life impairment across EQ-5D domains (OR&#xa0;=&#xa0;2.72, 95&#xa0;% CI: 1.60-4.63, p&#xa0;<&#xa0;0.001). Vaccinated individuals (7&#xa0;%) showed a non-significant trend toward better EQ-5D scores (p&#xa0;=&#xa0;0.116, 95&#xa0;% CI: 0.05 to 0.20).<br><br>CONCLUSIONS: Older age and hospitalization significantly predict long-term quality of life impairment in long COVID. Targeted interventions for these groups and robust post-recovery support are essential. Limitations include reliance on self-reported data, a low vaccination rate (7&#xa0;%), a 3-6 months follow-up, and a single-center design, which may limit generalizability. Multi-center studies with longer follow-ups and objective biomarkers are needed to enhance further understanding.},
}
@article {pmid40465774,
year = {2025},
author = {Salmam, I and Dubé, MO and Zahouani, I and Ramos, A and Desmeules, F and Best, KL and Roy, JS},
title = {The impact of long COVID on physical and cardiorespiratory parameters: A systematic review.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0318707},
pmid = {40465774},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/physiopathology/complications ; SARS-CoV-2 ; Respiratory Function Tests ; Adult ; Exercise Tolerance ; },
abstract = {BACKGROUND: Since the emergence of COVID-19, millions worldwide have continued to experience persistent symptoms months after infection. Among these, physical and cardiorespiratory impairments are frequently reported, but remain poorly understood. This systematic review aimed to identify and synthesize evidence regarding physical and cardiorespiratory impairments in individuals with long COVID, defined as symptoms persisting for at least three months post-infection.<br><br>METHODS AND FINDINGS: A structured search was conducted across the MEDLINE, Embase, CINAHL, and Web of Science databases to identify cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. Twenty-two studies involving 3,041 adults with long COVID were included. Critical appraisal using the JBI-APT indicated that most studies had clear inclusion criteria (17/22), well-defined study populations (17/22), and valid exposure measurements (16/22), though confounding factors were often unaddressed (9/22 unclear or not reported). Findings indicate that while adults with long COVID displayed normal pulmonary function at rest, including Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Total Lung Capacity (TLC), and resting Arterial oxygen saturation (SpO2), significant impairments in exercise capacity were identified. Notably, all studies assessing the 6-minute walk test (6MWT) reported reduced distances, consistently falling below the 50th percentile of normative values. Additionally, VO&#x2082;peak was decreased in most studies (7/10), falling below 80% of the predicted value, indicating impaired aerobic capacity. Lower Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) values were observed in three out of six studies, with values below 75% of predicted, suggesting impaired gas exchange efficiency during exertion.<br><br>CONCLUSION: Despite preserved resting lung function, these findings highlight significant physical deconditioning in Long COVID adults, with substantial reduction in exercise capacity. Routine assessments should include more sensitive measures, such as the 6MWT and VO&#x2082;peak, to detect subtle exercise limitations, even in patients with normal resting SpO&#x2082;, to better inform rehabilitation interventions.},
}
@article {pmid40465195,
year = {2025},
author = {Glass, KA and Giloteaux, L and Zhang, S and Hanson, MR},
title = {Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Clinical and translational medicine},
volume = {15},
number = {5},
pages = {e70346},
pmid = {40465195},
issn = {2001-1326},
support = {U54 AI178855/AI/NIAID NIH HHS/United States ; U54 NS105541/NS/NINDS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Male ; *Fatigue Syndrome, Chronic/physiopathology/metabolism ; *Extracellular Vesicles/metabolism ; *Endoplasmic Reticulum Stress/physiology ; Adult ; Proteomics/methods ; *Energy Metabolism/physiology ; *Exercise/physiology ; *Complement System Proteins/metabolism ; Middle Aged ; },
abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness characterized by post-exertional malaise (PEM), a worsening of symptoms following exertion. The biological mechanisms underlying PEM remain unclear. Extracellular vesicles (EVs) play a key role in cell-cell communication and may provide insight into ME/CFS pathophysiology post-exertion. Emerging evidence suggests similarities between ME/CFS and Long COVID, including PEM and overlapping immune and metabolic dysfunctions, highlighting the need for deeper mechanistic understanding.<br><br>METHODS: This study explores the EV proteome response to exercise in 10 males with ME/CFS and 12 well-matched sedentary male controls. Participants underwent a maximal cardiopulmonary exercise test, and plasma samples were collected at baseline, 15&#xa0;min, and 24&#xa0;h postexercise. EVs were isolated from plasma using size-exclusion chromatography and characterized with nanoparticle tracking analysis. EV protein abundance was quantified with untargeted proteomics (nanoLC-MS/MS). Comprehensive analyses included differential abundance, pathway enrichment, protein-protein interaction networks, and correlations between EV protein dynamics and clinical or exercise physiology data.<br><br>RESULTS: ME/CFS patients exhibited many significantly altered EV proteomic responses compared with controls, including downregulation of TCA cycle-related proteins and upregulation of complement system proteins at 15&#xa0;min postexercise. Changes in proteins involved in protein folding and the endoplasmic reticulum (ER) stress response during recovery were highly correlated with PEM severity, highlighting their potential as therapeutic targets. EV protein changes postexercise were also associated with disease severity and unrefreshing sleep. Correlations between EV protein levels and the exercise parameters VO&#x2082; peak and ventilatory anaerobic threshold were observed in controls but were absent in ME/CFS patients, suggesting disrupted EV-mediated physiological processes.<br><br>CONCLUSIONS: ME/CFS patients exhibit a maladaptive EV proteomic response to exercise, characterized by metabolic impairments, immune overactivation, and ER stress response dysregulation. These findings provide insight into the molecular basis of PEM and suggest promising targets for improving recovery and energy metabolism in ME/CFS.<br><br>KEY POINTS: EVs were isolated from plasma of ME/CFS patients and healthy controls at baseline, and 15 min and 24&#xa0;h postexercise. Untargeted proteomics revealed dysregulation in energy metabolism, the complement system, and the endoplasmic reticulum stress response. Changes in EV protein levels postexercise are associated with post-exertional malaise. These findings suggest promising therapeutic targets for post-exertional malaise and ME/CFS pathophysiology.},
}
@article {pmid40464778,
year = {2025},
author = {Leite Barbosa, N and Rangel Agra Oliveira, T and Nóbrega, LD and Araújo, TTF and Dos Santos Bezerra, SR and Oliveira, GM and Do Nascimento, RM and de Miranda Silva Nogueira, PA and Tomaz, AF and Do Nascimento Sales Figueiredo Fernandes, AT},
title = {Prevalence and characteristics of respiratory and cardiovascular sequelae in post-COVID-19 syndromes: a scoping review.},
journal = {Expert review of respiratory medicine},
volume = {19},
number = {9},
pages = {935-953},
doi = {10.1080/17476348.2025.2515992},
pmid = {40464778},
issn = {1747-6356},
mesh = {Humans ; *COVID-19/complications/epidemiology/therapy ; Prevalence ; *Cardiovascular Diseases/epidemiology/etiology ; *Dyspnea/epidemiology/etiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Cough/epidemiology ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Post acute and Long COVID-19 are public health issues, marked by persistent respiratory and cardiovascular symptoms such as dyspnea and palpitations. These complications often extend beyond the acute phase, affecting even individuals with mild or moderate COVID-19. This article reviews the clinical impact of long COVID-19 and emphasizes the need for a multidisciplinary approach to management.<br><br>AREAS COVERED: A comprehensive literature search was conducted through PubMed, Medline, CINAHL, SciELO, and LILACS to identify studies published up to 28 October 2024, reporting on respiratory and cardiovascular sequelae in long COVID-19. This review examines the prevalence and characteristics of persistent symptoms such as dyspnea, cough, and palpitations, as well as the associated risk factors and assessment methods.<br><br>EXPERT OPINION: Long COVID-19 represents a significant healthcare challenge, underscoring the need for standardized protocols for diagnosis and treatment. A multidisciplinary approach is crucial to address the diverse symptoms of affected patients. Future research should focus on understanding the underlying pathophysiology, and developing targeted therapeutic strategies to improve patient outcomes.},
}
@article {pmid40464158,
year = {2025},
author = {Lak, V and Sjöland, H and Adiels, M and Lundberg, CE and Robertson, J and Åberg, M and Alex, C and Lindgren, M and Rosengren, A},
title = {Preexisting symptoms increase the risk of developing long COVID during the SARS-CoV-2 pandemic.},
journal = {Journal of internal medicine},
volume = {298},
number = {2},
pages = {107-122},
pmid = {40464158},
issn = {1365-2796},
support = {2019-00193//Swedish Research Council/ ; 2020-05792//Swedish Research Council/ ; 2021-06525//Swedish Research Council/ ; 2023-02144//Swedish Research Council/ ; 2021-0345//Swedish Heart and Lung Foundation/ ; 2024-0678//Swedish Heart and Lung Foundation/ ; 2021-00304//Forskningsr&#xe5;det om H&#xe4;lsa, Arbetsliv och V&#xe4;lf&#xe4;rd/ ; ALFGBG-966211//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-1006439//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-942707//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-971608//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-943008//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Male ; Female ; Retrospective Studies ; Middle Aged ; Adult ; Aged ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Young Adult ; Adolescent ; Prevalence ; },
abstract = {BACKGROUND: Long COVID is defined as otherwise unexplained symptoms following a SARS-CoV-2 infection.<br><br>OBJECTIVE: To examine the prevalence of preexisting symptoms compatible with long COVID in individuals with a diagnosis of long COVID.<br><br>METHODS: This retrospective, observational study included the adult population (aged 18 years and older) in Region V&#xe4;stra G&#xf6;taland, with at least one recorded healthcare contact between January 1, 2020, and November 30, 2023, from a regional database comprising all levels of healthcare contacts. Data on long COVID, relevant symptoms before and after the pandemic started (2016-2023), and SARS-CoV-2 infection status were extracted using the International Classification of Diseases version 10 (ICD-10) codes. Individuals who had been hospitalized due to a SARS-CoV-2 infection were considered separately.<br><br>RESULTS: Out of 1,415,885 individuals, 9202 (0.6%) had been diagnosed with long COVID. Among the non-hospitalized individuals, the record of at least one of the relevant symptoms was more common in those with long COVID compared to those without it (57.6% vs. 36.3% for men and 71.6% vs. 50.4% for women), already before January 1, 2020. Among individuals with any relevant symptom, the odds ratios (ORs) of having long COVID were OR&#xa0;=&#xa0;2.28 (95% confidence interval [CI]&#xa0;=&#xa0;2.10-2.48) for men and OR&#xa0;=&#xa0;2.32 (95% CI&#xa0;=&#xa0;2.18-2.48 for women) after adjusting for age group, obesity, asthma, and anxiety, compared with individuals without any relevant symptom.<br><br>CONCLUSIONS: Individuals diagnosed with long COVID had more healthcare contacts for relevant symptoms even before the pandemic compared to individuals without long COVID.},
}
@article {pmid40463782,
year = {2025},
author = {Farr, E and Esterov, D and Kassmeyer, BA and Lennon, RJ and Bergquist, TF},
title = {Demographics, Clinical Characteristics, and Outcomes of a Post-Coronavirus-19 Sample After Cognitive Rehabilitation: A Case Series.},
journal = {Archives of rehabilitation research and clinical translation},
volume = {7},
number = {1},
pages = {100409},
pmid = {40463782},
issn = {2590-1095},
abstract = {The Coronavirus-19 pandemic has infected millions of people, resulting in ongoing symptoms now described as post-acute sequelae of SARS-COV2 infection (PASC). Persistent neurologic and behavioral sequelae including fatigue, depression, anxiety, sleep disorders, headache, memory loss, and cognitive complaints are common. Although there is increasing evidence related to treatment of physical symptoms such as fatigue through physical rehabilitation practices, to date there is very limited evidence about the efficacy of various treatment regimens directed at nonphysical symptoms such as cognitive concerns and behavioral sequelae. This case series discusses a series of 13 patients with PASC who underwent individualized multidisciplinary outpatient cognitive rehabilitation at a quaternary medical center. In this patient population, the median age was 46 years (Q1, Q3: 41, 50), 77% were women, and 85% were White. The median time from infection to treatment was 229 days (Q1, Q3: 117, 367) and median length of stay in the program was 4.9 months (Q1, Q3: 3.1, 6.3). A history of depression and anxiety was found in 38% and 46% of this population, respectively. On admission and at discharge, the Mayo-Portland Adaptability Inventory-4 Participation Index, the Satisfaction with Life Scale, the Patient Health Questionnaire-9, and the Neurobehavioral Symptom Inventory-22 were completed. After individualized outpatient cognitive therapy, no clear benefit was seen in any of the outcome measures. The ongoing investigation is important to better understand which approaches will benefit these patients.},
}
@article {pmid40463044,
year = {2025},
author = {Amer, HM and Shamseldin, MM and Faber, S and Eltobgy, M and Webb, A and El-Mergawy, R and Chamblee, M and Perez, R and Whitham, O and Badr, A and Gupta, G and Omran, J and Bissel, D and Yount, J and Cormet-Boyaka, E and Boyaka, PN and Li, J and Zhang, X and Peeples, ME and Mahesh, KC and Pietrzak, M and Seveau, S and Kokiko-Cochran, O and Amer, M and Barrientos, RM and Schamess, A and Oltz, E and Amer, AO},
title = {AI-based decoding of long covid cognitive impairments in mice using automated behavioral system and comparative transcriptomic analysis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.14.654036},
pmid = {40463044},
issn = {2692-8205},
abstract = {Long COVID (LC) following SARS-CoV-2 infection affects millions of individuals world-wide and manifests with a variety of symptoms including cognitive dysfunction also known as "brain fog". This is characterized by difficulties in executive functions, planning, decision-making, working memory, impairments in complex attention, loss of ability to learn new skills and perform sophisticated brain tasks. No effective treatment options currently exist for LC-related cognitive dysfunction. Here, we use the IntelliCage, which is an automated tracking system of cognitive functions, following SARS-CoV-2 infection in mice, measuring the ability of each mouse within a group to perform tasks that mimic complex human behaviors, such as planning, decision-making, cognitive flexibility, and working memory. Artificial intelligence and machine learning analyses of the tracking data classified LC mice into distinct behavioral categories from non-infected control mice, permitting precise identification and quantification of complex cognitive dysfunction in a controlled, replicable manner. Importantly, we find that brains from LC mice with cognitive dysfunction exhibit transcriptomic alterations similar to those observed in humans suffering from LC-related cognitive impairments, including altered expression of genes involved in learning, executive functions, synaptic functions, neurotransmitters and memory. Together, our findings establish a validated murine model and an automated unbiased approach to study LC-related cognitive dysfunction for the first time, and providing a valuable tool for screening potential treatments and therapeutic interventions.},
}
@article {pmid40462722,
year = {2025},
author = {Nielssen, I and Olson, S and Goulding, S and Bohja, S and Yu, M and Paguirigan, R and McEntee, E and Bruce, M and McKenzie, N and Fairie, P and Santana, MJ},
title = {What Are the Barriers and Supports to a Return to Health From Long COVID? A Qualitative Study Designed, Developed, and Conducted by Individuals With Lived Experience of Long COVID.},
journal = {Qualitative health research},
volume = {},
number = {},
pages = {10497323251337566},
doi = {10.1177/10497323251337566},
pmid = {40462722},
issn = {1552-7557},
abstract = {Long COVID is a debilitating and persistent illness that affects individuals in multiple and dynamic ways. Because of the significant physical, emotional, and economic impacts long COVID holds on individuals, their families, and society more broadly, it is imperative that a multi-faceted approach is taken to the long COVID research that aims to improve outcomes for those affected. Expertise about the barriers and supports to accessing appropriate, patient-centered care is best provided by those with lived experience. A Patient and Community Engagement Research (PaCER) team of student researchers, all with lived experience of long COVID, conducted a qualitative study to understand barriers and supports to a return to health for those living with long COVID. This online study was informed by Canada-wide participants all living with long COVID. Patient experience and perspective data were collected through peer-to-peer focus groups and semi-structured interviews. The team used a thematic and a thematic and narrative analysis approach to identify six themes: Challenges Within Medical Systems to Keep Pace With Novel Condition, Impact of Long COVID Condition on Mental Well-Being, Money Matters, Managing Personal Energy Capacity, Resources and Supports for Long COVID Care and Recovery, and Disregard Participants Felt Toward Their Health and Well-Being. They identified 21 subthemes. This patient-directed study yielded essential recommendations to supporting a return to health for those living with long COVID to enable them to re-engage with their previous family, social, employment, and other relational activities. In addition to demonstrating more inclusive approaches to including long COVID patients in the research that impacts them, the study results can inform more appropriate person-centered healthcare, planning, and policy for those living with, and for those who will be living with, long COVID going forward.},
}
@article {pmid40460818,
year = {2025},
author = {Drobinska, N and Nehme, M and Assal, F and Laffitte, E and Guessous, I and Lascano, AM},
title = {Small Fiber Neuropathy in Long COVID: A Cohort Study with Multimodal Assessment and Follow-Up.},
journal = {European neurology},
volume = {88},
number = {2},
pages = {52-63},
doi = {10.1159/000546015},
pmid = {40460818},
issn = {1421-9913},
mesh = {Humans ; Female ; *COVID-19/complications ; *Small Fiber Neuropathy/diagnosis/etiology/physiopathology ; Male ; Adult ; Middle Aged ; Follow-Up Studies ; Cohort Studies ; *Neuralgia/etiology/physiopathology/diagnosis ; Skin/pathology ; Laser-Evoked Potentials ; Galvanic Skin Response/physiology ; Biopsy ; SARS-CoV-2 ; Neural Conduction/physiology ; },
abstract = {INTRODUCTION: Given the increasing number of patients suffering from pain associated with dysautonomic symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we aimed to estimate the occurrence of small fiber neuropathy (SFN) in a cohort of long coronavirus disease 19 (COVID-19) patients reporting postinfectious neuropathic pain.<br><br>METHODS: The study cohort included 18 patients suffering from neuropathic pain (neuropathic pain score DN4 &#x2265;4) appearing after or during SARS-CoV-2 infection and lasting &#x2265;90 days; presenting normal nerve conduction studies excluding large fiber damage. Patients underwent multimodal SFN evaluation by skin biopsy, quantitative sensory testing (QST), laser evoked potential (LEP) recording and electrochemical skin conductance (ESC; Sudoscan).<br><br>RESULTS: Out of 18 patients, 17 were analyzed. Participants' ages averaged 44 &#xb1; 9 years, with 94% females. Fourteen (82%) had abnormal skin biopsy results. Notably, 12/17 (70%) patients presented with autonomic complaints, all of whom had abnormal skin biopsy results. At 6-month follow-up, 10/17 patients reported a subjective improvement in pain and/or dysautonomia with or without symptomatic pharmacological or non-pharmacological treatment. In our cohort, QST showed the highest sensibility (79%) and specificity (67%), followed by LEP (sensibility 71%, specificity 67%). ESC showed poor reliability in the screening of SFN with a sensibility of 7% and specificity of 50%.<br><br>CONCLUSION: The results of our study suggest that SFN may develop during or shortly after SARS-CoV-2 infection, provoking disabling sensory and dysautonomic symptoms that tend to persist for more than 6 months. Furthermore, our findings imply that noninvasive exams are a useful complement to biopsy in the diagnostic process of SFN.},
}
@article {pmid40458645,
year = {2025},
author = {Visconti, NRG and Rocha, NN and Nascimento, GS and Menário, CVB and Silva, JD and Martins, CM and Caruso-Neves, C and Cruz, FF and Rocco, PRM and Mello, FCQ and Lapa-E-Silva, JR},
title = {Elevated adipokines and myokines are associated with fatigue in long COVID patients.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1547886},
pmid = {40458645},
issn = {2296-858X},
abstract = {BACKGROUND: Persistent fatigue is one of the most common and debilitating symptoms experienced by patients recovering from COVID-19, contributing significantly to the burden of "long COVID" or post-COVID-19syndrome. However, the underlying pathophysiological mechanisms remain inadequately understood. Few studies have examined the association between fatigue and pulmonary or cardiac function, systemic biomarkers, or morphological changes in the lungs and diaphragm. Furthermore, the potential influence of vaccination on the persistence of fatigue has not been fully explored. This study aims to identify mechanisms contributing to post-COVID-19 fatigue.<br><br>METHODS: This prospective cohort study assessed clinical, laboratory, pulmonary, and cardiac parameters, as well as diaphragm ultrasound and pulmonary function, in patients with and without fatigue at least 4&#x202f;months after discharge from hospitalization due to COVID-19.<br><br>RESULTS: Of 88 patients evaluated, 34% reported new or worsening fatigue after recovering from COVID-19. Demographic characteristics, comorbidities, and vaccination status were similar between fatigued and non-fatigued groups. However, ICU admission during the acute phase of illness emerged as a significant risk factor for fatigue (OR 2.65; 95% CI, 1.03-6.94) in multivariable analysis. No significant differences were observed in lung function, diaphragm or lung ultrasound findings, or left ventricular systolic function between groups. Fatigue was associated with significantly elevated serum levels of myostatin and irisin, markers of muscle metabolism. Additionally, patients experiencing fatigue reported poorer functional capacity and significantly reduced quality of life, with lower scores in multiple domains of the SF-36 questionnaire, including general health, vitality, and mental health.<br><br>CONCLUSION: Post-COVID-19 fatigue is strongly associated with prior ICU admission and elevated levels of myostatin and irisin, implicating potential myopathic mechanisms in its persistence. The profound impact of fatigue on functional capacity and quality of life highlights the urgent need for further research to elucidate its pathophysiology and develop targeted therapeutic strategies. This study provides critical insights into the interplay between systemic and organ-specific factors contributing to fatigue, offering a foundation for future interventions to improve outcomes in patients with long COVID.},
}
@article {pmid40458610,
year = {2025},
author = {Liao, M and Cai, J and Zhu, F and Lan, Y and Xu, T and Guo, J and Xue, Q and Wen, Y and Zou, F and Zhang, Y and Zhang, S and Yan, Y and Ai, J and Cui, J and Zhang, W},
title = {Meta-transcriptomics Reveals Dysbiosis of the Respiratory Microbiome in Older Adults with Long COVID.},
journal = {Research (Washington, D.C.)},
volume = {8},
number = {},
pages = {0720},
pmid = {40458610},
issn = {2639-5274},
abstract = {Limited research has investigated the connection between long COVID (LC) and the respiratory microbiome, particularly in older adults. This study aimed to characterize the respiratory microbiome of older LC patients (with an average age of 65 years old), through meta-transcriptomic sequencing of 201 individual samples. Marked differences in microbial diversity were observed between LC and non-LC patients, including disruptions in both pathogenic bacteria and fungi. Importantly, viral taxa, such as Herpes simplex virus type 1 and Human coronavirus 229E, were more frequently detected in LC patients, indicating the vulnerability of LC patients to viral infections. Functional annotation at the expression level revealed notable differences in microbial metabolism with alterations observed in pathways related to tryptophan-serotonin metabolism in LC patients. These findings underscore the altered microbial landscape, especially in older adults who developed LC, and fill the gap for the potentially clinical roles played by the respiratory microbiome.},
}
@article {pmid40458265,
year = {2025},
author = {Sasso, EM and Eaton-Fitch, N and Smith, P and Muraki, K and Marshall-Gradisnik, S},
title = {Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1582967},
pmid = {40458265},
issn = {2296-889X},
abstract = {INTRODUCTION: Long COVID is a multisystemic condition that includes neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, independent of the severity or duration of the acute SARS-CoV-2 infection. Dysfunctional Transient Receptor Potential Melastatin 3 (TRPM3) ion channels are associated with the pathophysiology of long COVID due to reduced calcium (Ca[2+]) influx, negatively impacting cellular processes in diverse systems. Accumulating evidence suggests the potential therapeutic benefits of low-dose naltrexone (LDN) for people suffering from long COVID. Our study aimed to investigate the efficacy of LDN in restoring TRPM3 ion channel function in natural killer (NK) cells from long COVID patients.<br><br>METHODS: NK cells were isolated from nine individuals with long COVID, nine healthy controls, and nine individuals with long COVID who were administered LDN (3-4.5 mg/day). Electrophysiological experiments were conducted to assess TRPM3 ion channel functions modulated by pregnenolone sulfate (PregS) and ononetin.<br><br>RESULTS: The findings from this current research are the first to demonstrate that long COVID patients treated with LDN have restored TRPM3 ion channel function and validate previous reports of TRPM3 ion channel dysfunction in NK cells from individuals with long COVID not on treatment. There was no significant difference in TRPM3 currents between long COVID patients treated with LDN and healthy controls (HC), in either PregS-induced current amplitude (p > 0.9999) or resistance to ononetin (p > 0.9999).<br><br>DISCUSSION: Overall, our findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca[2+] influx necessary for homeostatic cellular processes.},
}
@article {pmid40458104,
year = {2025},
author = {Morera, M and Arévalo, A and Garriga, C and Corral-Magaña, M and García-Arqué, MC and Gragea-Nocete, M and Pérez Díaz, C and Roca, R and Llistosella, M},
title = {Assessing a multicomponent intervention to improve quality of life in individuals with Long COVID (COVIDL/MIQoL): study protocol for a randomized controlled trial.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1604971},
pmid = {40458104},
issn = {2296-2565},
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/psychology ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Female ; Male ; Adult ; Middle Aged ; },
abstract = {INTRODUCTION: The impact of Long COVID on the quality of life of affected individuals is significant, therefore, the aim of this study is to analyse the effectiveness of the multicomponent intervention protocol to improve quality of life in individuals with Long COVID.<br><br>METHODS: A randomized controlled trial with two parallel arms will be conducted. Individuals diagnosed with Long COVID, but without any severe mental disorders, will be recruited. The sample size is estimated to be around 54 participants per group. A psychologist and a physiotherapist will carry out the intervention between January and March 2025. Participants will receive specific training in psycho-education and physical rehabilitation consisting of 18 sessions, to be held twice a week. Data collection will start in January 2025 and will finish in October 2025. Data will be collected: at baseline, before the intervention (T0); after 9&#x202f;weeks, post-intervention (T1); and after 24&#x202f;weeks, follow-up (T2), and will assess quality of live, well-being, anxiety, depression resilience, fatigue, and physical activity. An intention-to-treat analysis will be performed and the effect size will be calculated using Cohen's d. All statistical analyses will be performed using R software version 4.2.2, with a 95% confidence level and a statistical significance level of p&#x202f;<&#x202f;0.05.<br><br>DISCUSSION/CONCLUSION: The results will be disseminated to individuals with Long COVID and their families throughout their primary health care center. Healthcare professionals will receive specific training to be able to develop and implement the intervention. In addition, the results will be disseminated to the scientific community via conferences and publications.<br><br>CLINICAL TRIAL REGISTRATION: https://register.clinicaltrials.gov/prs/beta/studies/S000ENW100000080/recordSummary, Identifier NCT06492590.},
}
@article {pmid40457068,
year = {2025},
author = {Bonnefoy, PB and Pascal, P and Ceyrat, Q and Burg, S and Razzouk-Cadet, M and Moreau Triby, C and Biancheri Mounicq, I and Bourre, JC and Salaun, PY and Le Roux, PY},
title = {Interest of ventilation/perfusion SPECT/CT in patients with post-COVID condition: a multicenter observational study.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {53},
number = {1},
pages = {531-543},
pmid = {40457068},
issn = {1619-7089},
}
@article {pmid40455450,
year = {2025},
author = {Guilliams, KP},
title = {The Importance of Playing the Long Game With Long COVID and Long-Term Hospital Recovery.},
journal = {JAMA network open},
volume = {8},
number = {6},
pages = {e2512495},
doi = {10.1001/jamanetworkopen.2025.12495},
pmid = {40455450},
issn = {2574-3805},
}
@article {pmid40454660,
year = {2025},
author = {Friedly, JL and Roman, J and Long, J and Grewal, M and Chopra, A and Bender, J and Gentile, N and Knowles, LM and Herring, T and O'Loughlin, K and Rivera, N},
title = {The healing role of music and arts in long COVID: A patient perspective.},
journal = {PM &amp; R : the journal of injury, function, and rehabilitation},
volume = {17},
number = {6},
pages = {709-715},
doi = {10.1002/pmrj.13430},
pmid = {40454660},
issn = {1934-1563},
support = {U18 HS029905/HS/AHRQ HHS/United States ; 1U18HS029905-01/HS/AHRQ HHS/United States ; },
}
@article {pmid40454145,
year = {2025},
author = {Mainous, AG and Bao, S and Goldman, M},
title = {Editorial: Long COVID: pathogenesis, diagnosis and clinical management.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1615692},
pmid = {40454145},
issn = {2296-858X},
}
@article {pmid40453253,
year = {2025},
author = {Boorle, NVLD and Kurra, NC and Gandrakota, N and Modi, K and Sudireddy, K and Irfan, SA and Jain, A and Parikh, PA and Jillella, D},
title = {Central Nervous System Manifestations of Long COVID: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83247},
pmid = {40453253},
issn = {2168-8184},
abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been one of the most widespread and devastating global pandemics, impacting hundreds of millions of people worldwide. After the cessation of active infection, the disease continues to have a disabling impact due to the persistence of fatigue, brain fog, anxiety, and depression - among the most common symptoms. This study explores the progression of neurological symptoms over 12 months and beyond following an initial diagnosis of COVID-19. Through an electronic search of eligible studies from PubMed, the Cochrane Trial Register, and Google Scholar, 10 studies were included for qualitative analysis. The systematic review highlights the similarities and differences in findings across the included studies. Olfactory dysfunction was prevalent in 0.9%-51% of individuals, and taste impairment was observed in 1.1%-21.3%. At 12 months, anxiety was more prevalent (3.5%-29%) than depression (3.5%-26%). Fatigue was the predominant neurocognitive complaint in 56% of individuals with severe COVID-19. Nearly half of individuals reported sleep difficulties. Memory impairment, followed by headaches and dizziness, also constitutes neurocognitive symptoms reported at 12 months. Our study found that there is a significant neurological burden one year following the diagnosis of COVID-19. Further studies exploring the pathological mechanisms of long-term COVID-19 are necessary to better delineate the mechanisms behind several long-term neurological manifestations of COVID-19.},
}
@article {pmid40450635,
year = {2025},
author = {Oh, S and An, S and Park, K and Lee, S and Han, YM and Koh, SJ and Lee, J and Gim, H and Kim, D and Seo, H},
title = {Gut Microbial Signatures in Long COVID: Potential Biomarkers and Therapeutic Targets.},
journal = {Infectious diseases and therapy},
volume = {14},
number = {7},
pages = {1461-1475},
pmid = {40450635},
issn = {2193-8229},
support = {2022R1A2C1010356//National Research Foundation of Korea/ ; RS-2023-00227939//National Research Foundation of Korea/ ; },
abstract = {INTRODUCTION: Following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, symptoms can persist for more than 12 weeks in over 10% of patients in a condition known as long coronavirus disease (COVID). Gut microbiota dysbiosis is correlated with long COVID, but the specific relationship between long COVID and the gut microbiome remains unclear. Here, we aimed to investigate connections between the gut microbiota and long COVID severity.<br><br>METHODS: Fecal samples were collected from 31 patients with long COVID, 14 with COVID-19 but not long COVID, and 23 healthy controls. The mean interval between COVID-19 diagnosis and sample collection was 65.5&#xa0;(range: 13.0-110.3)&#xa0;weeks for patients with long COVID and 74.8&#xa0;(range: 50.7-110.4)&#xa0;weeks for positive control group. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Patient-reported outcomes were used to comprehensively assess long COVID symptom severity.<br><br>RESULTS: Symptom severity was higher in patients with severe initial infections and significantly correlated with serum triglyceride, fasting blood glucose, and high-density lipoprotein-cholesterol levels. Results showed distinct microbial profiles in patients with long COVID. Leuconostoc, Actinomyces, and Granulicatella were significantly enriched, and they accurately distinguished patients with long COVID from controls, indicating their potential as long COVID biomarkers. Particular gut bacteria were significantly correlated with certain systemic, gastrointestinal, otolaryngologic, and visual symptoms. Parabacteroides, Eubacterium ventriosum group, and Rothia abundance was correlated with blood biomarkers that influence long COVID development, including total and low-density lipoprotein cholesterol and basophil levels.<br><br>CONCLUSIONS: The gut microbial signature of patients with long COVID differed from that of healthy controls. Certain microbial genera showed significant differences between patients with long COVID and controls, suggesting potential as preliminary biomarkers and therapeutic targets for long COVID pending validation in larger studies.},
}
@article {pmid40449327,
year = {2025},
author = {Robineau, O and Hüe, S and Surenaud, M and Lemogne, C and Dorival, C and Wiernik, E and Brami, S and Nicol, J and de Lamballerie, X and Blanché, H and Deleuze, JF and Ribet, C and Goldberg, M and Severi, G and Touvier, M and Zins, M and Levy, Y and Lelievre, JD and Carrat, F},
title = {Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort study.},
journal = {EBioMedicine},
volume = {117},
number = {},
pages = {105792},
pmid = {40449327},
issn = {2352-3964},
mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; Female ; Male ; Middle Aged ; SARS-CoV-2 ; Prospective Studies ; Biomarkers/blood ; Post-Acute COVID-19 Syndrome ; Aged ; Adult ; },
abstract = {BACKGROUND: Several studies reported long-term consequences of severe COVID-19. However, pathophysiological mechanisms of Post-Acute Sequelae following COVID-19 (PASC) in patients with mild acute COVID-19 have been less investigated. Specifically, the link between PASC and immuno-inflammatory abnormalities is inconsistent in the literature. The hypothesis that different pathophysiological mechanisms could explain the persistent symptoms needs to be explored.<br><br>METHODS: The COPER cohort is a prospective study that included participants with PASC and with a history of COVID-19 without persistent symptoms. None were hospitalised for COVID-19. Participants underwent two home visits six months apart for biological sample collection and completed questionnaires on medical history, infection, vaccination, symptoms, and mental health. The study analysed association between persistent symptoms and 14 blood biomarkers, comparing participants with PASC with recovered participants.<br><br>FINDINGS: Between June and November 2022, 1000 participants were included in the study, 199 were excluded due to missing data or sample (35), SARS-CoV-2 infection less than 3 months (36) or lack of known SARS-CoV-2 infection and negative serology (128), with two groups analysed: recovered (n = 490), PASC (n = 311). Participants with PASC were more frequently women, had a higher BMI and a median number of 3 persistent symptoms, with common symptoms being asthenia, dyspnoea, cough, and sleep disorders. Biological analysis revealed significant associations between certain PACS symptoms and biomarkers of viral activation (IFN&#x3b3;, IP-10), COVID-19 severity (CD163) and vascular activation (VCAM-1, ICAM-1), mainly in subjects whose symptoms had lasted less than a year. However, these associations did not persist over time.<br><br>INTERPRETATION: The results suggest a polymorphic and dynamic pathophysiology according to symptoms and time since infection. Other hypotheses, beyond those related to persistent inflammation, should be explored.<br><br>FUNDING: French Ministry of Health and Prevention and the French Ministry of Higher Education, Research and Innovation.},
}
@article {pmid40448188,
year = {2025},
author = {Mendenhall, E and Kamau, LW and Kenworthy, N and Bosire, EN},
title = {Digital activism in Kenya: moving from the digital center to the digital periphery of Long Covid experience.},
journal = {Globalization and health},
volume = {21},
number = {1},
pages = {33},
pmid = {40448188},
issn = {1744-8603},
mesh = {Humans ; Kenya/epidemiology ; *COVID-19/psychology/epidemiology ; Female ; *Social Networking ; *Digital Technology ; },
abstract = {Digital activism around Long Covid has reverberated around the globe, as patients, researchers, and clinicians worked together to understand the chronic condition. However, Long Covid networks, much like other social networks, have hierarchies and barriers that can impede equitable access. In this article, we examine how the global digital center and periphery shape how people with Long Covid connect to networks to learn about their illness symptoms, diagnoses, treatments, and experiences. We introduce case narratives of two Kenyan women-one elite Nairobian who was connected to the digital center and another middle class woman who connected with her through a peripheral digital community-to describe how elite patients were engaged at the digital center, and non-elite patients were engaged in the periphery with digital and non-digital connections through which they cultivated other social networks to communicate, share, and experience their illness experiences. The Kenyan case study introduces a context where people have sophisticated digital lives and are engaged in global information networks. Yet, we argue that some Long Covid patients' experiences are impossible to divorce from the digital activism that has drawn together a remarkable global patient community, causing a ripple effect on how people define and experience the self and illness throughout the world. We conclude that many Kenyans may be engaging with digital networks differently and from different places of geographic, cultural, linguistic, and technological power, possibly cultivating divergent idioms, interpretations, and experiences of the post-viral condition. This demonstrates not only how social networks function at the digital periphery but also the complexities situated within the periphery itself, which is at important social nodes, connected to the digital center.},
}
@article {pmid40447142,
year = {2025},
author = {Vreeman, ECA and Pillay, J and Burgess, JK},
title = {Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis.},
journal = {Pharmacology &amp; therapeutics},
volume = {272},
number = {},
pages = {108891},
doi = {10.1016/j.pharmthera.2025.108891},
pmid = {40447142},
issn = {1879-016X},
mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/drug therapy/virology ; SARS-CoV-2 ; Lung/pathology ; },
abstract = {After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis. Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.},
}
@article {pmid40446594,
year = {2025},
author = {Koller, K and Herold, R and Morawa, E and Erim, Y},
title = {Coping competence and health outcomes in post-COVID: A prospective study on the role of adaptive strategies in symptom management and physical and mental health.},
journal = {Journal of psychosomatic research},
volume = {194},
number = {},
pages = {112152},
doi = {10.1016/j.jpsychores.2025.112152},
pmid = {40446594},
issn = {1879-1360},
mesh = {Humans ; Female ; *Adaptation, Psychological/physiology ; Male ; Middle Aged ; Prospective Studies ; *COVID-19/psychology/complications ; Adult ; *Fatigue/psychology/etiology ; *Depression/psychology/etiology ; *Mental Health ; SARS-CoV-2 ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC), characterized by persistent symptoms like fatigue, cognitive impairments, and mental health problems, requires effective coping strategies for symptom management, yet their impact on health outcomes in PASC patients remains unclear. This study examines differences in coping strategies across subgroups, changes over time, and their relationship with PASC symptoms and physical and mental health.<br><br>METHODS: In a prospective study, conducted at the Post-COVID Center of the University Hospital of Erlangen, patients were assessed at baseline (T0) and follow-up (T1; M&#xa0;=&#xa0;4.46&#xa0;months, SD&#xa0;=&#xa0;2.27). Coping strategies were measured using the Patient Competence Questionnaire-2 (PCQ-2), including coping competence, religious/spiritual coping, healthy lifestyle, information-seeking, and adaptability. PASC symptom severity (PCS score), fatigue (FSS), post-exertional malaise (DSQ-PEM), and depressive symptoms (PHQ-9) were also assessed.<br><br>RESULTS: Among 339 participants (age: M&#xa0;=&#xa0;45.51&#xa0;years, SD&#xa0;=&#xa0;11.96; 70.2&#xa0;% women) coping competence improved significantly over time, while no notable changes were observed in the other factors and overall patient competence. Women scored higher than men in religious/spiritual coping, coping competence, and healthy lifestyle (all p&#xa0;<&#xa0;.001). Higher education levels were associated with higher scores in coping competence, information-seeking, and healthy lifestyle (p&#xa0;=&#xa0;.028, p&#xa0;=&#xa0;.014 and p&#xa0;=&#xa0;.012, respectively). Higher coping competence at T0 significantly predicted fewer symptoms of fatigue and depression (p&#xa0;=&#xa0;.021 and p&#xa0;<&#xa0;.001, respectively) at T1, whereas higher adaptability at T0 was associated with more severe fatigue, PEM, and depression at T1 (p&#xa0;<&#xa0;.001, p&#xa0;=&#xa0;.001 and p&#xa0;=&#xa0;.020, respectively).<br><br>CONCLUSION: Strengthening coping competence may improve symptom management and severity in PASC patients, highlighting the need for targeted interventions.<br><br>TRIAL REGISTRATION: DRKS00033621, https://drks.de/search/de/trial/DRKS00033621.},
}
@article {pmid40446093,
year = {2026},
author = {Niebauer, JH and Ahmet, I and Sarah, S and Christophe, C and Michael, K and Simon, S and John, F and Marc, S and Michael, L and Alexander, Z and Rosmarie, V and Sabine, H and Silvia, CR and Christian, K and Wolfgang, H and Christoph, W and Diana, B},
title = {Cardiopulmonary long-term effects 30 months after severe COVID-19 infection.},
journal = {European heart journal. Quality of care &amp; clinical outcomes},
volume = {12},
number = {1},
pages = {136-146},
doi = {10.1093/ehjqcco/qcaf035},
pmid = {40446093},
issn = {2058-1742},
support = {22186//Medical Scientific Fund/ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology/diagnosis ; Male ; Female ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; Follow-Up Studies ; Aged ; Tomography, X-Ray Computed ; Echocardiography ; Respiratory Function Tests ; Electrocardiography ; Time Factors ; Adult ; },
abstract = {AIMS: The aim of this study was to assess symptoms and long-term cardiopulmonary impairments over a period of up to 30 months following severe COVID-19 infection.<br><br>METHODS AND RESULTS: This prospective multicenter cohort study included 200 patients hospitalized between February 2020 and October 2021 with a PCR-confirmed COVID-19 infection. Follow-up examinations 6, 18, and 30 months post-discharge included electrocardiogram, transthoracic echocardiography, cardiac magnetic resonance imaging, chest computed tomography (CT) scan, pulmonary function test (PFT), 6-min walk test, and a laboratory panel. 200 patients completed their 6-month follow-up after discharge and those with pathological findings on cardiopulmonary imaging received additional follow-ups at 18 and 30 months (170 and 139 patients, respectively).At 30 months, most of the cardiopulmonary imaging abnormalities had resolved. Only two patients with previously reduced left ventricular function had persistent mild impairment at 30 months [6 months: n = 15 (8%)]. Pericardial effusion resolved in all patients but one [6 months: n = 28 (17%)]. Signs of pericarditis and myocarditis had already regressed at the 18-month follow-up [6 months: n = 7 (5%)].Chest CT scans showed partial improvement: only one patient had complete resolution at 30 months, while the remaining patients [30 months: n = 17 (94%)] developed minor fibrotic and scarred tissue [6 months: n = 41 (24%)].Long COVID incidence was high with 73% at 6 months and still 49% at 30 months, with no clear predictors identified.<br><br>CONCLUSION: Even though cardiopulmonary functional and structural abnormalities regressed over time, almost half of the patients still suffered from Long COVID at 30 months. The disconnect between pathological cardiopulmonary findings and reported symptoms, continues to pose a persistent clinical challenge in the understanding and managing Long COVID.},
}
@article {pmid40444408,
year = {2025},
author = {Wang, E and Patel, ZM},
title = {Paxlovid Is Associated With Lower Rates of Long COVID-19 Smell and Taste Disorders.},
journal = {International forum of allergy &amp; rhinology},
volume = {15},
number = {10},
pages = {1094-1100},
doi = {10.1002/alr.23612},
pmid = {40444408},
issn = {2042-6984},
mesh = {Humans ; Male ; Female ; *Olfaction Disorders/prevention &amp; control/epidemiology/etiology ; *Taste Disorders/prevention &amp; control/epidemiology/etiology ; Case-Control Studies ; Middle Aged ; *COVID-19/complications ; SARS-CoV-2 ; Adult ; Aged ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Research is needed on treatments that prevent progression to long COVID-19 olfactory and gustatory dysfunction, which millions continue to suffer from. We sought to explore the utility of Paxlovid in decreasing rates of long COVID-19 smell and taste loss.<br><br>DESIGN: This case-control study at a single tertiary medical center examined patients who were acutely infected with COVID-19 and received Paxlovid from December 2021 to September 2023 and age-matched infected patients who did not receive Paxlovid. Occurrence of nasal congestion, rhinorrhea, facial pain/pressure and smell/taste loss were recorded both in the acute (<30 days for nasal congestion, rhinorrhea, facial pain/pressure; <90 days for smell/taste loss) and the long-term settings for both groups. Chi-square and t-tests were used to compare the two groups.<br><br>RESULTS: A total of 846 individuals had complete data (Paxlovid: 423, non-Paxlovid: 423). Significantly more individuals in the Paxlovid group experienced nasal congestion (p < 0.001) and rhinorrhea (p = 0.006) in the acute setting. However, resolution of these symptoms after 30 days did not differ between the Paxlovid and non-Paxlovid groups (p = 0.375 and p = 0.316, respectively). Facial pressure did not differ between the two groups in either the acute or long-term setting (p = 0.077 and p = 0.315). In the acute setting, there was no significant difference between groups in the number of patients experiencing olfactory/gustatory changes (p = 0.487). After taking Paxlovid however, individuals were less likely to experience long-term olfactory/gustatory changes (p < 0.001).<br><br>CONCLUSIONS: Early intervention with Paxlovid may decrease the risk of long COVID-19 smell/taste changes. Further study with a randomized controlled trial would help providers know more definitively if they should consider this utility in preventing long-term smell and taste loss.},
}
@article {pmid40444353,
year = {2025},
author = {Kisiangani, I and Jornada Ben, &#xc2; and Wynberg, E and Wami, W and Iddi, S and Kinya, I and Vassall, A and Kyobutungi, C and Ziraba, A and Njeru, J and Mugenda, O and Kiguoya, MW and Kimondo, M and Githua, G and de Jong, MD and Mohamed, SF and Asiki, G and Schultsz, C},
title = {Recovery and long-term health outcomes of SARS-CoV-2 infection in a prospective cohort in an urban setting, Kenya.},
journal = {Global health action},
volume = {18},
number = {1},
pages = {2500795},
pmid = {40444353},
issn = {1654-9880},
mesh = {Humans ; Kenya/epidemiology ; *COVID-19/epidemiology/physiopathology ; Female ; Adult ; Male ; Prospective Studies ; Middle Aged ; Severity of Illness Index ; Young Adult ; SARS-CoV-2 ; Urban Population/statistics &amp; numerical data ; Adolescent ; Time Factors ; },
abstract = {BACKGROUND: Evidence on long COVID remains limited in sub-Saharan countries.<br><br>OBJECTIVE: This study explored the occurrence of COVID-19-related symptoms and factors affecting recovery and long COVID severity in Nairobi, Kenya.<br><br>METHODS: A prospective cohort of individuals testing positive for SARS-CoV-2 between February 2022 and February 2023 was followed until June 2023. COVID-19-related symptoms were assessed every three months. Time to recovery was analyzed using survival analysis, while factors affecting recovery factors and long COVID severity using Cox proportional hazard and Poisson regression, respectively.<br><br>RESULTS: Among 291 participants (median age 34, 59.1% female), 42 (14%) had severe/critical infection. At 6 and 12&#x2009;months post-positive PCR, 53.1% and 33.5% had&#x2009;&#x2265;&#x2009;1 COVID-19-related symptoms, respectively. Fatigue (40.2%), pain (36.8%), sore throat (36.8%), headaches (36.4%), and loss of strength (31.6%) were most common. Median time to recovery was longer for severe/critical cases than mild/moderate (234 vs 206&#x2009;days, p&#x2009;=&#x2009;0.016). Participants aged 40-64&#x2009;years experienced slower recovery than those aged&#x2009;<&#x2009;40&#x2009;years (aHR&#x2009;=&#x2009;0.635 [95%CI, 0.429;0.941]). Participants with tertiary education recovered faster than those with primary education (aHR&#x2009;=&#x2009;1.869 [95%CI, 1.050;3.327]). Long COVID severity was associated with female sex (aIRR&#x2009;=&#x2009;1.418 [95%CI; 1.078;1.864]), tertiary education (aIRR, 0.489 [95%CI, 0.415;0.576]), and&#x2009;&#x2265;&#x2009;1 comorbidity (aIRR&#x2009;=&#x2009;2.415 [95%CI, 1.639;3.559]).<br><br>CONCLUSIONS: Six months post-infection, half had lingering symptoms, with a third still affected after a year. Recovery was faster in younger, educated individuals, while severe long COVID was more common in women, those with low education and pre-existing conditions. The burden of long COVID in Kenya requires support for vulnerable groups.},
}
@article {pmid40443486,
year = {2025},
author = {Islam, MW and Rahman, E and Hossain, KMA and Hossain, MZ},
title = {Scope of rehabilitation for patients with long COVID symptoms in Bangladesh.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1572351},
pmid = {40443486},
issn = {2673-6861},
abstract = {BACKGROUND: The Bangladeshi healthcare system had planned to meet the long-term rehabilitation needs of people who had suffered due to COVID, as well as those whose health and level of activity had declined during the COVID pandemic. The goal is to apply the COVID-19 Yorkshire Rehabilitation Scale (C-YRS) to ascertain the number of health domains in which a person with PCS should undergo rehabilitation.<br><br>METHODS: We carried out a quantitative cross-sectional study. The eight administrative divisions provided the pool of participants for selecting the 409 people comprised by the stratified sampling. We collected data using a semi-structured questionnaire that included sociodemographics, a symptoms checklist, and the C-YRS.<br><br>RESULTS: The most common post-COVID symptoms among the participants were fatigue (34.3%), muscle pain (20%), and dyspnea (12.2%). The comparison between pre- and postinfection symptoms revealed a notable increase in symptom severity and functional impairments. The study also found a significant relationship between symptom severity and place of residence (p&#x2009;<&#x2009;0.5). The study found that the severity of symptoms was mild (30.5% (n&#x2009;=&#x2009;90), moderate 55.3% (n&#x2009;=&#x2009;186), and severe 14.2% (n&#x2009;=&#x2009;94). We also looked for correlations between symptom severity, functional impairment, and health. It showed a significant positive correlation between symptom scores and functional difficulty scores (0.889, p&#x2009;<&#x2009;0.001), while there was a significant negative correlation between symptom scores and overall health (-0.658, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Severity phenotypes can aid in the stratification of people with PCS for targeted therapies and rehabilitation care planning.},
}
@article {pmid40441540,
year = {2025},
author = {Posharina, T and Varonen, M and Jarva, H and Kanerva, M and Liira, H and Laakso, SM},
title = {Serum antineuronal antibodies in patients with post-COVID-19 condition - association to intensive care.},
journal = {Brain, behavior, and immunity},
volume = {129},
number = {},
pages = {87-91},
doi = {10.1016/j.bbi.2025.05.026},
pmid = {40441540},
issn = {1090-2139},
mesh = {Humans ; Female ; Male ; *COVID-19/immunology/complications/blood ; *Autoantibodies/blood/cerebrospinal fluid ; Middle Aged ; Prospective Studies ; Aged ; SARS-CoV-2 ; Critical Care ; Adult ; Nerve Tissue Proteins/immunology ; Nerve Growth Factors/immunology ; Membrane Proteins ; },
abstract = {Post-COVID-19 condition (PCC), characterized by persistent symptoms following SARS-CoV-2 infection, is a global health challenge. Neurological symptoms are common in PCC, and immune-mediated mechanisms have been proposed as potential contributors. We set out to systematically explore serum antineuronal antibodies in patients with PCC and clinical factors associated with seropositivity. Our prospective, single-center cohort study included adult patients with a confirmed SARS-CoV-2 infection at least three months prior and a diagnosis of PCC. Serum and cerebrospinal fluid (CSF) samples were analyzed for the presence of antineuronal antibodies. A control group with confirmed SARS-CoV-2 infection but without PCC symptoms was included, age-, sex- and time from acute infection to sampling -matched to seropositive cases of PCC. Among 314 consecutive patients with PCC, 38 (12.1 %) tested positive for serum antineuronal antibodies. CSF analysis was performed for a subset; however, no intrathecal autoantibodies were detected. The most prevalent serum autoantibodies targeted CASPR-2 (n = 7, 18.9 %), neurofascin-186 (n = 5, 13.2 %), and glycine receptor (n = 4, 10.8 %). Multinomial logistic regression identified intensive care unit (ICU) admission during acute COVID-19 as the only significant predictor of autoantibody positivity (OR 3.4; 95 % CI: 1.0-10.4). Of the 35 control subjects, two (5.7 %) tested seropositive: one with low titer myelin oligodendrocyte glycoprotein antibodies and another with borderline myelin antibody levels. None of the patients met criteria for autoimmune encephalitis, and neurological assessments and brain magnetic resonance imaging were unremarkable. Neuropsychological testing showed a trend toward impairments in attention and executive functions among seropositive individuals. Thus, there was no significant difference in the prevalence of serum antineuronal antibodies in PCC compared to post-infection controls, and the association between seropositivity and ICU admission suggested systemic immune activation rather than a specific autoantibody-mediated mechanism. It remains unclear whether observed neuropsychological deficits are attributable to autoantibodies or the effects of critical illness.},
}
@article {pmid40439483,
year = {2025},
author = {Krishnan, JA and Cao, B and Chotirmall, SH and Ely, EW and Openshaw, P and Roche, N and Waterer, G},
title = {Using the 2024 National Academies of Science, Engineering, and Medicine Definition of Long COVID: Implications for Pulmonary and Critical Care Medicine.},
journal = {American journal of respiratory and critical care medicine},
volume = {211},
number = {8},
pages = {1391-1396},
pmid = {40439483},
issn = {1535-4970},
}
@article {pmid40438846,
year = {2025},
author = {Idris Fadul, AA and Osman Mohamed, AA and Mohammed Ahmed, AAS and Elmobark, S and Merghani Hammour, AS and Elgaleel Khir Elsiad, NMN and Mohammed Elhaj, EA},
title = {Post-coronavirus Disease 2019 (COVID-19) Cardiovascular Manifestations: A Systematic Review of Long-Term Risks and Outcomes.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83083},
pmid = {40438846},
issn = {2168-8184},
abstract = {Emerging evidence suggests that coronavirus disease 2019 (COVID-19) survivors face increased risks of cardiovascular complications, but the long-term risks, underlying mechanisms, and clinical implications remain incompletely characterized. This systematic review synthesizes current evidence on post-COVID-19 cardiovascular manifestations, evaluating their incidence, pathophysiology, and outcomes. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Fifteen observational studies (cohort, case-control, cross-sectional) meeting predefined eligibility criteria, confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, cardiovascular outcomes assessed ≥4 weeks post-infection, sample sizes >10, and peer-reviewed publication, were included. The risk of bias was assessed using the Newcastle-Ottawa Scale. The multinational studies (United States, Europe, Asia, South America) involved diverse populations (n=80-8,126,462), with follow-up durations ranging from three to 24 months. Mechanisms such as endothelial dysfunction, myocardial inflammation, and autonomic dysregulation were consistently supported across studies via imaging (e.g., cardiac MRI) and biomarkers (e.g., troponin, C-reactive protein (CRP)). Persistent arrhythmias and subclinical myocardial injury were directly demonstrated in 40-60% of patients. Worse outcomes were associated with hospitalization during acute infection, preexisting cardiovascular disease, and metabolic syndrome. Heterogeneity in follow-up durations may limit the detection of very-late-onset complications, though risks remained elevated across all intervals. Individualized management strategies should include cardiovascular imaging (echocardiography, MRI), biomarker profiling, and tailored pharmacotherapy (anti-inflammatory agents, anticoagulants). The ethical rationale for randomized trials is now strengthened by the clear evidence of long-term risks; ongoing trials are testing targeted anti-inflammatory and anticoagulant regimens. These findings underscore the necessity of systematic cardiovascular surveillance and risk-stratified care for COVID-19 survivors. Future research should prioritize extended follow-up studies and randomized controlled trials (RCTs) to optimize interventions for this growing population.},
}
@article {pmid40435383,
year = {2025},
author = {Nairn, B and Tsakanikas, V and Gordon, B and Karapintzou, E and Kaski, D and Fotiadis, DI and Bamiou, DE},
title = {Smart Wearable Technologies for Balance Rehabilitation in Older Adults at Risk of Falls: Scoping Review and Comparative Analysis.},
journal = {JMIR rehabilitation and assistive technologies},
volume = {12},
number = {},
pages = {e69589},
pmid = {40435383},
issn = {2369-2529},
abstract = {BACKGROUND: Falls among older adults are a significant public health concern, often leading to severe injuries, decreased quality of life, and substantial health care costs. Smart wearable technologies for balance rehabilitation present a promising avenue for addressing the falls epidemic, capable of providing detailed objective movement data, engaging visuals, and real-time feedback. With the recent and rapid evolution of innovative technologies, including artificial intelligence (AI), augmented reality (AR) or virtual reality (VR), and motion tracking, there is a need to evaluate the market to identify the most effective and accessible smart balance systems currently available.<br><br>OBJECTIVE: This study aims to evaluate the current landscape of smart wearable technology systems for balance rehabilitation in older adults at risk of falls. In addition, it aims to compare market-available systems to the telerehabilitation of balance clinical and economic decision support system (TeleRehab DSS), a recently developed smart balance system.<br><br>METHODS: A scoping review and strengths, weaknesses, opportunities, and threats (SWOT) analysis was completed, exploring the landscape of smart balance systems in older adults at risk of falls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, electronic databases PubMed, MEDLINE, and Cochrane were systematically searched for articles in English from July 1, 2014, to July 1, 2024. Gray literature searches of relevant institutions and web pages were also conducted. The database search and commercial systems were then compared against the TeleRehab DSS in a SWOT analysis.<br><br>RESULTS: The scoping review yielded 17 systems that met the inclusion criteria; 10 investigational systems and 7 commercially available systems. Out of 10 studies, only 1 reported the use of intelligent learning or AI, 8 studies reported the use of motion tracking, and 9 studies used virtual reality. Of the studies incorporating motion tracking, 3 provided feedback as either visual or auditory. All but 2 studies reported the use of gamification, and 7 studies incorporated balance exercises. In total, 2 studies reported remote delivery, with 5 being clinician-supervised and 4 providing a clinician report. The SWOT analysis of TeleRehab DSS against the 7 market-available smart balance systems revealed several unique advantages, including personalized therapy with AI-DSS, AR for real-world interaction, enhanced clinician involvement, and comprehensive data analytics.<br><br>CONCLUSIONS: The findings from this scoping review highlight the rapid evolution of smart balance systems, yet significant gaps remain in AI integration, remote accessibility, and clinician-driven data analytics. Despite limitations such as cost, accessibility, and user training requirements, TeleRehab DSS emerges as a significant innovation, addressing many of these gaps through AI-driven personalization, AR for real-world interaction, and real-time clinician monitoring. These features position it as a next-generation solution that aligns closely with the evolving needs of patients and clinicians. The results of this review provide valuable insights for future research, supporting the need for further validation studies and the development of more intelligent and accessible balance rehabilitation technologies.},
}
@article {pmid40434132,
year = {2025},
author = {Metcalfe, J and Scoullar, MJL and Whyler, NCA and Balkin, H and Tippett, E},
title = {Beyond time as the healer: action in long COVID treatment to improve patient outcomes.},
journal = {Internal medicine journal},
volume = {55},
number = {7},
pages = {1203-1207},
doi = {10.1111/imj.70099},
pmid = {40434132},
issn = {1445-5994},
mesh = {Humans ; *COVID-19/therapy ; Patient-Centered Care ; Post-Acute COVID-19 Syndrome ; *Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; },
abstract = {Long COVID is complex and disabling. Despite emerging therapies, the lack of guidelines and clinician awareness delays treatment. This paper highlights options available now to improve function and quality of life. We call for a symptom-focused, person-centred approach that incorporates lived experience and clinical judgement to bridge the gap between evidence and care. Time alone is not the answer.},
}
@article {pmid40433308,
year = {2025},
author = {Chowdhury, SR and Islam, N and Zhou, Q and Hasan, MK and Chowdhury, MR and Siemieniuk, RA and Agarwal, A and Brignardello-Petersen, R and Agoritsas, T and Olav Vandvik, P and Zeraatkar, D and Guyatt, G},
title = {Metformin for covid-19: systematic review and meta-analysis of randomised controlled trials.},
journal = {BMJ medicine},
volume = {4},
number = {1},
pages = {e001126},
pmid = {40433308},
issn = {2754-0413},
abstract = {OBJECTIVE: To summarise the effects of metformin on covid-19 to inform a World Health Organization (WHO) clinical practice guideline.<br><br>DESIGN: Systematic review and meta-analysis.<br><br>DATA SOURCES: As part of a living systematic review and network meta-analysis of drug treatments for covid-19 (covid-19 LNMA), a search was performed of the WHO covid-19 database, six Chinese databases, and the Epistemonikos Foundation's Living Overview of the Evidence covid-19 Repository (covid-19 L-OVE).<br><br>Randomised controlled trials that compared metformin with placebo in patients with acute covid-19 infection.<br><br>DATA SYNTHESIS: Frequentist pairwise meta-analyses were performed using the restricted maximum likelihood random effects model. The effects of interventions on selected outcomes were summarised using risk ratios, risk difference, and mean difference when appropriate, along with their corresponding 95% confidence intervals (CIs). To estimate absolute effects, the control arm event rate was used as the baseline risk. The risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool and the certainty of evidence using the GRADE (grading of recommendations assessment, development and evaluation) approach, with the minimally important difference in effect as the threshold.<br><br>RESULTS: Three randomised controlled trials of 1869 patients were included; one study provided long term follow-up on long covid. Metformin might have little or no impact on mortality (risk ratio 0.76, 95% CI 0.30 to 1.90; risk difference 3 fewer per 1000, 95% CI 8 fewer to 11 more; low certainty). The effects of metformin on admission to hospital because of covid-19 remain uncertain (risk ratio 0.74, 95% CI 0.28 to 1.95; risk difference 15 fewer per 1000, 95% CI 42 fewer to 55 more; very low certainty). Metformin results in little or no difference in adverse effects leading to discontinuation (risk difference 0.2 more per 1000, 95% CI 2.7 fewer to 3.1 more; high certainty). Metformin might decrease the development of long covid (risk ratio 0.6, 95% CI 0.4 to 0.9; risk difference 41 fewer per 1000, 95% CI 62 fewer to 10 fewer; low certainty). However, the effect is based on a single trial of 1126 patients, which has a high risk of bias owing to missing data, and nearly half of the participants were unvaccinated.<br><br>CONCLUSIONS: Current evidence based on randomised trials suggests no significant effect of metformin on acute clinical outcomes in patients with non-severe covid-19. Metformin might reduce the incidence of long covid when used to treat patients with non-severe acute covid-19 infection, but this was suggested by low certainty evidence from a single trial.},
}
@article {pmid40431734,
year = {2025},
author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS},
title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431734},
issn = {1999-4915},
support = {25-BR-02-03//Korea Brain Research Institute/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.},
}
@article {pmid40431631,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431631},
issn = {1999-4915},
mesh = {*Spike Glycoprotein, Coronavirus/metabolism/genetics ; Humans ; *COVID-19/virology/physiopathology/complications/metabolism ; *SARS-CoV-2/metabolism/genetics/physiology ; *Receptors, Virus/metabolism ; Protein Binding ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has had a significant impact on global health through both acute illness, referred to as coronavirus disease 2019 (COVID-19), and chronic conditions (long COVID or post-acute sequelae of COVID-19, PASC). Despite substantial advancements in preventing severe COVID-19 cases through vaccination, the rise in the prevalence of long COVID syndrome and a notable degree of genomic mutation, primarily in the S protein, underscores the necessity for a deeper understanding of the underlying pathophysiological mechanisms related to the S protein of SARS-CoV-2. In this review, the latest part of this series, we investigate the potential pathophysiological molecular mechanisms triggered by the interaction between the spike protein and cellular receptors. Therefore, this review aims to provide a differential and focused view on the mechanisms potentially activated by the binding of the spike protein to canonical and non-canonical receptors for SARS-CoV-2, together with their possible interactions and effects on the pathogenesis of long COVID.},
}
@article {pmid40431629,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Saldanha-Araujo, F and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 1: Impact of Spike Protein in Pathophysiological Mechanisms of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431629},
issn = {1999-4915},
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/complications/virology/physiopathology/pathology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has resulted in more than 700 million cases and nearly 7 million deaths worldwide. Although vaccination efforts have effectively reduced mortality and transmission rates, a significant proportion of recovered patients-up to 40%-develop long COVID syndrome (LC) or post-acute sequelae of COVID-19 infection (PASC). LC is characterized by the persistence or emergence of new symptoms following initial SARS-CoV-2 infection, affecting the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Despite the broad range of clinical symptoms that have been described, the risk factors and pathogenic mechanisms behind LC remain unclear. This review, the first of a two-part series, is distinguished by the discussion of the role of the SARS-CoV-2 spike protein in the primary mechanisms underlying the pathophysiology of LC.},
}
@article {pmid40431432,
year = {2025},
author = {Matsuda, Y and Sakurada, Y and Nakano, Y and Otsuka, Y and Tokumasu, K and Honda, H and Soejima, Y and Yokota, Y and Takase, R and Omura, D and Otsuka, F},
title = {Clinical Characteristics of Vitamin D Deficiency Detected in Long COVID Patients During the Omicron Phase.},
journal = {Nutrients},
volume = {17},
number = {10},
pages = {},
pmid = {40431432},
issn = {2072-6643},
support = {23fk0108585h0001//Japan Agency for Medical Research and Development/ ; },
mesh = {Humans ; Female ; *Vitamin D Deficiency/blood/complications/epidemiology/diagnosis ; Male ; *COVID-19/complications/blood/epidemiology ; Retrospective Studies ; Middle Aged ; Vitamin D/blood/analogs &amp; derivatives ; SARS-CoV-2 ; Aged ; Adult ; },
abstract = {Background: To characterize the clinical significance of vitamin D deficiency (VDD) detected in long COVID, a retrospective observational study was performed for outpatients who visited our clinic during the period from May 2024 to November 2024. Methods: Clinical trends in long COVID patients diagnosed with VDD who showed serum concentrations of 25-hydroxyvitamin D (25-OHD) lower than 20 ng/mL were compared with those in long COVID patients in a non-deficient vitamin D (NDD) group. Results: Of 126 patients with long COVID, 97 patients (female: 50) who had been infected during the Omicron phase were included. Sixty-six patients (68%) were classified in the VDD group. The median serum concentrations of 25-OHD were 14.8 ng/mL in the VDD group and 22.9 ng/mL in the NDD group. There were no significant differences between the two groups in terms of age, gender, BMI, severity of COVID-19, period after infection and vaccination history. Although the levels of serum calcium and phosphate were not significantly different between the two groups, the percentages of patients in the VDD group who complained of dizziness, memory impairment, palpitation and appetite loss were larger than those in the NDD group. Of note, the patients who complained of palpitation showed significantly lower concentrations of serum 25-OHD than those in the patients without palpitation (median: 11.9 vs. 17.3 ng/mL). Moreover, patients in the VDD group had significantly higher scores for physical and mental fatigue as well as higher scores for depressive symptoms. Conclusions: Collectively, VDD is involved in clinical manifestations of long COVID, particularly symptoms of palpitation, fatigue and depression.},
}
@article {pmid40430532,
year = {2025},
author = {Kell, DB and Pretorius, E and Zhao, H},
title = {A Direct Relationship Between 'Blood Stasis' and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {5},
pages = {},
pmid = {40430532},
issn = {1424-8247},
abstract = {'Blood stasis' (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (). Similar concepts exist in Traditional Korean Medicine ('Eohyul') and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down ('stasis') of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke.},
}
@article {pmid40430247,
year = {2025},
author = {Takács, J and Deák, D and Seregély, B and Koller, A},
title = {Cognitive Slowing, Dysfunction in Verbal Working Memory, Divided Attention and Response Inhibition in Post COVID-19 Condition in Young Adults.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {5},
pages = {},
pmid = {40430247},
issn = {2075-1729},
support = {TKP2020-NKA-17//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; TKP2021-EGA-37//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; OTKA K 132596//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; TKP2021-EGA-25//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; EK&#xd6;P-2024-151//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; Post-Covid 2021-34//HUNGARIAN ACADEMY OF SCIENCES/ ; &#xda;NKP-22-4-II-SE-4//NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR INNOVATION AND TECHNOLOGY FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; },
abstract = {After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive function. A total of 107 young adults, university students aged 18-34 years, participated. In total, 68.2% had contracted SARS-CoV-2; 21.9% showed PCC. Three groups were compared: no-C19 (COVID-19-negative controls), C19 (COVID-19-recovered without PCC) and PCC. Attention and executive function were measured with the Vienna Test System (Schuhfried[®], Mödling, Austria). In verbal working memory, the PCC group had a significantly lower performance with a moderate effect. The rate of below-average performance was higher in PCC (56.2%) compared to no-C19 (20.6%) and C19 (15.8%). In divided attention and response inhibition, PCC also showed lower performance, 62.5% and 37.5%, respectively, than no-C19 and C19. The co-occurrence of decreased cognitive functions was pronounced in PCC. The present study revealed significant long-lasting cognitive dysfunction in PCC in young adults, two years after COVID-19 infection. Verbal working memory was significantly impaired, and a lower performance was found in divided attention and response inhibition. In addition, there was an increased reaction time in most cognitive tasks, demonstrating cognitive slowing in young people with PCC.},
}
@article {pmid40430160,
year = {2025},
author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I},
title = {Vitamin D and COVID-19: Clinical Evidence and Immunological Insights.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {5},
pages = {},
pmid = {40430160},
issn = {2075-1729},
abstract = {Vitamin D has emerged as a potential modulator of immune responses, sparking interest in its role in COVID-19 susceptibility and clinical outcomes. This review synthesizes current clinical evidence and explores immunological insights into the relationship between vitamin D levels and COVID-19 infection severity. Epidemiological studies indicate an inverse correlation between vitamin D deficiency and an increased risk of severe disease, hospitalization, and mortality in COVID-19 patients. Immunologically, vitamin D exerts regulatory effects on both innate and adaptive immunity, enhancing antimicrobial defense mechanisms, reducing excessive inflammatory responses, and potentially mitigating cytokine storm events observed in severe COVID-19 cases. Despite promising observational data, clinical trials evaluating vitamin D supplementation have shown mixed results, underscoring the need for standardized dosing regimens and patient stratification. Future research should focus on large-scale randomized controlled trials to conclusively determine the therapeutic potential and optimal supplementation strategies for vitamin D in managing COVID-19.},
}
@article {pmid40430026,
year = {2025},
author = {Martín-Martínez, E and Gil-Perotin, S and Giménez-Orenga, K and Barea-Moya, L and Oltra, E},
title = {HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40430026},
issn = {1422-0067},
support = {CIAICO 2021/103//Generalitat Valenciana/ ; ACIF2021/179//Generalitat Valenciana/ ; },
mesh = {Humans ; *Rituximab/therapeutic use ; Male ; *Endogenous Retroviruses/genetics ; *Multiple Sclerosis/drug therapy/virology ; Adult ; *Fatigue Syndrome, Chronic/drug therapy/virology ; COVID-19 ; },
abstract = {This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments. Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient's blood supportive of an altered immune system. Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.},
}
@article {pmid40429947,
year = {2025},
author = {Madè, A and Piella, SN and Ranucci, M and Gaetano, C and Renna, LV and Cardani, R and Spinetti, G and Milani, V and Martelli, F},
title = {LEF1-AS1 Deregulation in the Peripheral Blood of Patients with Persistent Post-COVID Symptoms.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429947},
issn = {1422-0067},
support = {Ricerca Corrente 2024 1.07.128//Ministero della Salute/ ; RF-2019-12368521//Ministero della Salute/ ; POS-T4 CAL.HUB.RIA T4-AN-09//Ministero della Salute/ ; Monica Stupino fund//FMM/ ; PNRRMAD-2022-12375790//Next Generation EU-NRRP M6C2 Inv. 2.1/ ; EU PNRR/2022/C9/MCID/I8//Next Generation EU-NRRP M6C2 Inv. 2.1/ ; Ricerca Corrente and 5Xmille to the IRCCS MultiMedica 2024//Ministero della Salute/ ; },
mesh = {Humans ; *COVID-19/blood/genetics ; Male ; Middle Aged ; *RNA, Long Noncoding/blood/genetics ; Case-Control Studies ; Female ; MicroRNAs/genetics/blood ; SARS-CoV-2 ; Biomarkers/blood ; *Lymphoid Enhancer-Binding Factor 1/genetics/blood ; Aged ; Leukocytes, Mononuclear/metabolism ; Adult ; },
abstract = {Long COVID denotes the persistence of symptoms after acute SARS-CoV-2 infection lasting for at least two months without another identifiable cause. Affecting an estimated 15% of COVID-19 patients, long COVID manifests in a wide range of symptoms. Despite extensive research on its one-year effects, limited data exist beyond 12 months. Due to the different manifestations of long COVID, its diagnosis can be challenging. Identifying potential mechanistic contributors and biomarkers would be highly valuable. Recent studies have highlighted the potential of noncoding RNAs (ncRNAs) as biomarkers for disease stratification in COVID-19. Specifically, we have recently identified miR-144-3p and a subset of lncRNAs as candidates for assessing disease severity and outcomes in COVID-19. This nested case-control study extends such investigations to 98 long COVID patients recruited 18 months after hospitalization, exploring the relationship between circulating ncRNA expression and persistent symptoms. While miR-144-3p, HCG18, and lncCEACAM21 expression did not differ between symptomatic and asymptomatic patients, LEF1-AS1 was downregulated in the peripheral blood mononuclear cells (PBMCs) of symptomatic patients. Of note, multiple LEF1-AS1 isoforms and LEF1 sense transcript levels were reduced and negatively correlated with relevant clinical markers. While further studies are needed, our discoveries offer new perspectives on the diagnosis and management of persistent long COVID.},
}
@article {pmid40429836,
year = {2025},
author = {Fernandez, JA and Han, Q and Rajczewski, AT and Kono, T and Weirath, NA and Lee, AS and Rahim, A and Tretyakova, NY},
title = {Multi-Omics Analysis of the Epigenetic Effects of Inflammation in Murine Type II Pneumocytes.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429836},
issn = {1422-0067},
support = {CA095039 and CA248019/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Lipopolysaccharides ; *Epigenesis, Genetic ; DNA Methylation ; *Alveolar Epithelial Cells/metabolism/pathology/drug effects ; *Inflammation/genetics/metabolism/pathology/chemically induced ; Lung Neoplasms/genetics/pathology/metabolism ; Multiomics ; },
abstract = {Chronic inflammation plays a central role in the pathogenesis of lung diseases including asthma, long COVID, chronic obstructive pulmonary disease (COPD), and lung cancer. Lipopolysaccharide (LPS) is a potent inflammatory agent produced by Gram-negative bacteria and also found in cigarette smoke. Our earlier study revealed that the intranasal exposure of A/J mice to LPS for 7 days altered gene expression levels in alveolar Type II epithelial cells (AECIIs), which serve as precursors to lung adenocarcinoma and are also preferentially targeted by SARS-CoV-2. In the present work, we employed a comprehensive multi-omics approach to characterize changes in DNA methylation/hydroxymethylation, gene expression, and global protein abundances in the AECIIs of A/J mice following the sub-chronic exposure to LPS and after a 4-week recovery period. Exposure to LPS led to hypermethylation at regulatory elements within the genome such as enhancer regions and expression changes in genes known to play a role in lung cancer tumorigenesis. Changes in protein abundance were consistent with an inflammatory phenotype and also included tumor suppressor proteins. Integration of the multi-omics data resulted in a model where LPS-driven inflammation in AECIIs triggers epigenetic changes that, along with genetic mutations, may contribute to lung cancer development.},
}
@article {pmid40429727,
year = {2025},
author = {Ignacio-Mejía, I and Bandala, C and González-Zamora, JF and Chavez-Galan, L and Buendia-Roldan, I and Pérez-Torres, K and Rodríguez-Díaz, MZ and Pacheco-Tobón, DX and Quintero-Fabián, S and Vargas-Hernández, MA and Carrasco-Vargas, H and Falfán-Valencia, R and Pérez-Rubio, G and Hernández-Lara, KA and Gómez-Manzo, S and Ortega-Cuellar, D and Ignacio-Mejía, F and Cárdenas-Rodríguez, N},
title = {Association of Vitamin D Supplementation with Glutathione Peroxidase (GPx) Activity, Interleukine-6 (IL-6) Levels, and Anxiety and Depression Scores in Patients with Post-COVID-19 Condition.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429727},
issn = {1422-0067},
support = {2022/C-015//Instituto Nacional de Pediatria/ ; C32-22//Instituto Nacional de Enfermedades Respiratorias Ismael Cos&#xed;o Villegas/ ; },
mesh = {Humans ; *Glutathione Peroxidase/blood/metabolism ; *Interleukin-6/blood ; Male ; Female ; *Anxiety/drug therapy/etiology/blood ; *Depression/etiology/drug therapy/blood ; *Dietary Supplements ; *COVID-19/complications/psychology/blood ; Middle Aged ; *Vitamin D/administration &amp; dosage ; Adult ; SARS-CoV-2 ; Aged ; },
abstract = {Coronavirus disease 2019 (COVID-19) presents with various symptoms, and some patients develop post-COVID-19 condition (PCC). Vitamin D has shown therapeutic potential in COVID-19 and may offer benefits for PCC. The aim of this study was to evaluate the differences associated with two supplementation strategies (bolus and daily) on interleukin-6 (IL-6) levels, glutathione peroxidase (GPx) activity, and clinical outcomes in PCC patients, regardless of whether target 25 (OH) D levels reached the ideal range. We conducted a self-controlled study in which 54 participants with PCC were supplemented with vitamin D3 (n = 28 bolus and n = 26 daily) for 2 months. Blood samples were collected to measure IL-6 levels and GPx activity using spectrophotometric methods. The Hospital Anxiety and Depression Scale (HADS) was used to assess mental function. Both bolus and daily vitamin D supplementation were significantly associated with increased GPx activity and decreased IL-6 levels. Daily supplementation was additionally associated with a significant reduction in anxiety and depression scores. However, neither regimen was associated with improvements in cough, dyspnea, or fatigue. These findings suggest a potential association between vitamin D supplementation and improvements in antioxidant and neuropsychiatric parameters in PCC, possibly mediated by its immunomodulatory and antioxidant properties. Further placebo-controlled trials are warranted to determine whether these observed associations reflect causal relationships.},
}
@article {pmid40429707,
year = {2025},
author = {Semo, D and Shomanova, Z and Sindermann, J and Mohr, M and Evers, G and Motloch, LJ and Reinecke, H and Godfrey, R and Pistulli, R},
title = {Persistent Monocytic Bioenergetic Impairment and Mitochondrial DNA Damage in PASC Patients with Cardiovascular Complications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429707},
issn = {1422-0067},
support = {SEED/018/23//IZKF SEED/ ; GO121222//Innovative Medizinische Forschung/ ; },
mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; *Energy Metabolism ; *DNA, Mitochondrial/genetics ; *DNA Damage ; *Cardiovascular Diseases/genetics/metabolism ; *Post-Acute COVID-19 Syndrome/genetics/immunology/metabolism ; Lipopolysaccharide Receptors/immunology ; Oxidative Stress ; Spike Glycoprotein, Coronavirus/genetics/metabolism ; Reactive Oxygen Species/metabolism ; Membrane Potential, Mitochondrial ; *Monocytes/immunology ; },
abstract = {Cardiovascular complications are a hallmark of Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial dysfunction in immune cells as a key contributor. This study investigated whether CD14[++] monocytes from long COVID patients exhibit bioenergetic impairment, mitochondrial DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms in PASC. CD14[++] monocytes were isolated from 14 long COVID patients with cardiovascular symptoms (e.g., dyspnea, angina) and 10 age-matched controls with similar cardiovascular risk profiles. Mitochondrial function was assessed using a Seahorse Agilent Analyzer under basal conditions and after oxidative stress induction with buthionine sulfoximine (BSO). Mitochondrial membrane potential was measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity via qPCR, and reactive oxygen species (ROS) dynamics via Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy monocytes to SARS-CoV-2 spike protein to evaluate direct viral effects. CD14[++] monocytes from long COVID patients with cardiovascular symptoms (n = 14) exhibited profound mitochondrial dysfunction compared to age-matched controls (n = 10). Under oxidative stress induced by buthionine sulfoximine (BSO), long COVID monocytes failed to upregulate basal respiration (9.5 vs. 30.4 pmol/min in controls, p = 0.0043), showed a 65% reduction in maximal respiration (p = 0.4035, ns) and demonstrated a 70% loss of spare respiratory capacity (p = 0.4143, ns) with significantly impaired adaptation to BSO challenge (long COVID + BSO: 9.9 vs. control + BSO: 54 pmol/min, p = 0.0091). Proton leak, a protective mechanism against ROS overproduction, was blunted in long COVID monocytes (3-fold vs. 13-fold elevation in controls, p = 0.0294). Paradoxically, long COVID monocytes showed reduced ROS accumulation after BSO treatment (6% decrease vs. 1.2-fold increase in controls, p = 0.0015) and elevated mitochondrial membrane potential (157 vs. 113.7 TMRE fluorescence, p = 0.0179), which remained stable under oxidative stress. mtDNA analysis revealed severe depletion (80% reduction, p < 0.001) and region-specific damage, with 75% and 70% reductions in amplification efficiency for regions C and D (p < 0.05), respectively. In contrast, exposure of healthy monocytes to SARS-CoV-2 spike protein did not recapitulate these defects, with preserved basal respiration, ATP production, and spare respiratory capacity, though coupling efficiency under oxidative stress was reduced (p < 0.05). These findings suggest that mitochondrial dysfunction in long COVID syndrome arises from maladaptive host responses rather than direct viral toxicity, characterized by bioenergetic failure, impaired stress adaptation, and mitochondrial genomic instability. This study identifies persistent mitochondrial dysfunction in long COVID monocytes as a critical driver of cardiovascular complications in PASC. Key defects-bioenergetic failure, impaired stress adaptation and mtDNA damage-correlate with clinical symptoms like heart failure and exercise intolerance. The stable elevation of mitochondrial membrane potential and resistance to ROS induction suggest maladaptive remodeling of mitochondrial physiology. These findings position mitochondrial resilience as a therapeutic target, with potential strategies including antioxidants, mtDNA repair agents or metabolic modulators. The dissociation between spike protein exposure and mitochondrial dysfunction highlights the need to explore host-directed mechanisms in PASC pathophysiology. This work advances our understanding of long COVID cardiovascular sequelae and provides a foundation for biomarker development and targeted interventions to mitigate long-term morbidity.},
}
@article {pmid40428115,
year = {2025},
author = {Jiang, S and Loomba, J and Zhou, A and Sharma, S and Sengupta, S and Liu, J and Brown, D and On Behalf Of N C Consortium, },
title = {A Bayesian Survival Analysis on Long COVID and Non-Long COVID Patients: A Cohort Study Using National COVID Cohort Collaborative (N3C) Data.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
pmid = {40428115},
issn = {2306-5354},
support = {75N95023D00001/TR/NCATS NIH HHS/United States ; },
abstract = {Since the outbreak of the COVID-19 pandemic in 2020, numerous studies have focused on the long-term effects of COVID infection. On 1 October 2021, the Centers for Disease Control (CDC) implemented a new code in the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) for reporting 'Post COVID-19 condition, unspecified (U09.9)'. This change indicated that the CDC recognized Long COVID as a real illness with associated chronic conditions. The National COVID Cohort Collaborative (N3C) provides researchers with abundant electronic health record (EHR) data by harmonizing EHR data across more than 80 different clinical organizations in the United States. This paper describes the creation of a COVID-positive N3C cohort balanced by the presence or absence of Long COVID (U09.9) and evaluates whether or not documented Long COVID (U09.9) is associated with decreased survival length.},
}
@article {pmid40427869,
year = {2025},
author = {Joseph, G},
title = {The Impact of Physical Activity on Long COVID Symptoms Among College Students: A Retrospective Study.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {5},
pages = {},
pmid = {40427869},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/epidemiology ; Retrospective Studies ; *Exercise ; Male ; *Students/statistics &amp; numerical data ; Female ; Universities ; Cross-Sectional Studies ; Young Adult ; Adult ; SARS-CoV-2 ; Adolescent ; },
abstract = {Millions worldwide suffer from long COVID, which affects daily life and impairs multiple organs. Younger adults report symptoms more frequently than older adults. Since physical activity enhances overall health, this study examines whether regular exercise reduces long COVID severity in college students. This cross-sectional retrospective study surveyed 309 teacher-training college students about their long COVID symptoms and physical activity levels. Participants were categorized based on activity levels, and symptom differences were analyzed. Among respondents, 44 (14.4%) reported long COVID symptoms, with fatigue being the most common (13.3%). Students engaging in regular, intense physical activity did not experience fewer symptoms than less active students (1.83 ± 0.85; 1.75 ± 0.89, p = 0.376). However, physical education students reported fewer symptoms than students in other programs (6.7% vs. 17.4%). Greater self-reported participation in physical activity was not associated with less reported long COVID symptoms among college-aged students; however, students enrolled in physical education programs-who integrate physical activity into their daily routines as part of their academic curriculum-reported fewer symptoms, suggesting that sustained, structured physical activity may contribute to reduced symptom burden. Further research is needed to explore this relationship.},
}
@article {pmid40427844,
year = {2025},
author = {Sommer, SB and Dietrich, MS and Barroso, JV},
title = {The Development and Initial Validation of the Memorial Symptom Assessment Scale-Long COVID (MSAS-LC): A Promising Tool for Measuring Long COVID.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {5},
pages = {},
pmid = {40427844},
issn = {1660-4601},
support = {//Julia Eleanor Blair Chenault Endowed Chair, Vanderbilt University School of Nursing/ ; },
mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; *Symptom Assessment/methods ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Prevalence ; Severity of Illness Index ; United States/epidemiology ; Reproducibility of Results ; },
abstract = {Long COVID remains a public health challenge, impacting over 65 million people globally and manifesting as persistent, multisystemic symptoms that complicate both diagnosis and treatment. To address the need for a standardized, patient-centered assessment tool, this study introduces the Memorial Symptom Assessment Scale-Long COVID (MSAS-LC), which evaluates symptom prevalence, frequency, severity, and distress. The MSAS-LC was developed by modifying the Memorial Symptom Assessment Scale to include 45 prevalent Long COVID symptoms. A cross-sectional survey of 261 U.S. adults (129 with Long COVID and 131 without) assessed validity and group differences. Symptom prevalence was analyzed using logistic regression, while symptom burden (frequency, severity, and distress) was compared using generalized linear models. Participants with Long COVID reported significantly higher symptom prevalence and burden across all systems. Memory problems (73.4% vs. 30.5%; OR = 6.29, p < 0.001) and post-exertional fatigue (OR = 8.55, p < 0.001) were among the most burdensome symptoms. These findings offer preliminary evidence supporting the potential utility of MSAS-LC and underscore the continued public health relevance of individual and collective symptom presentations. The findings suggest the distinct symptom burden, emphasizing the importance of future research to inform diagnostic and treatment strategies. With continued validation, the MSAS-LC may contribute to improved symptom monitoring and care planning in clinical and public health settings.},
}
@article {pmid40426703,
year = {2025},
author = {Rudroff, T},
title = {Digital Biomarkers and AI for Remote Monitoring of Fatigue Progression in Neurological Disorders: Bridging Mechanisms to Clinical Applications.},
journal = {Brain sciences},
volume = {15},
number = {5},
pages = {},
pmid = {40426703},
issn = {2076-3425},
abstract = {Digital biomarkers for fatigue monitoring in neurological disorders represent an innovative approach to bridge the gap between mechanistic understanding and clinical application. This perspective paper examines how smartphone-derived measures, analyzed through artificial intelligence methods, can transform fatigue assessment from subjective, episodic reporting to continuous, objective monitoring. The proposed framework for smartphone-based digital phenotyping captures passive data (movement patterns, device interactions, and sleep metrics) and active assessments (ecological momentary assessments, cognitive tests, and voice analysis). These digital biomarkers can be validated through a multimodal approach connecting them to neuroimaging markers, clinical assessments, performance measures, and patient-reported experiences. Building on the previous research on frontal-striatal metabolism in multiple sclerosis and Long-COVID-19 patients, digital biomarkers could enable early warning systems for fatigue episodes, objective treatment response monitoring, and personalized fatigue management strategies. Implementation considerations include privacy protection, equity concerns, and regulatory pathways. By integrating smartphone-derived digital biomarkers with AI analysis approaches, the future envisions fatigue in neurological disorders no longer as an invisible, subjective experience but rather as a quantifiable, treatable phenomenon with established neural correlates and effective interventions. This transformative approach has significant potential to enhance both clinical care and the research for millions affected by disabling fatigue symptoms.},
}
@article {pmid40423990,
year = {2025},
author = {Gross, RS and Carmilani, M and Stockwell, MS},
title = {Long COVID in Young Children, School-Aged Children, and Teens.},
journal = {JAMA pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamapediatrics.2025.1415},
pmid = {40423990},
issn = {2168-6211},
}
@article {pmid40420202,
year = {2025},
author = {Maeda, H and Igarashi, A and Kuwamitsu, O and Morimoto, K},
title = {Comparison of long-term health-related quality of life and symptoms between COVID-19 patients and test-negative controls during the Omicron-predominant period in Japan.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {136},
pmid = {40420202},
issn = {0778-7367},
support = {21HA2008, 23HA2017//the Ministry of Health, Labour and Welfare/ ; },
abstract = {BACKGROUND: Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affect health-related quality of life (HRQoL) and impose a substantial burden on society. While previous studies showed that both coronavirus disease 2019 (COVID-19) patients and patients with acute respiratory symptoms but negative for SARS-CoV-2 experienced persistent symptoms, evidence comparing the long-term HRQoL of COVID-19 patients with test-negative controls for SARS-CoV-2 remains limited. This study aimed to compare symptoms and HRQoL using EQ-5D-5L in both acute and chronic phases between COVID-19 patients and test-negative controls for SARS-CoV-2 during the Omicron-predominant period in Japan.<br><br>METHODS: Individuals aged &#x2265;18 years tested for SARS-CoV-2 with COVID-19-like symptoms at a clinic in Tokyo, Japan, between January 2022 and January 2023, were invited an online survey. Individuals who tested positive and negative for SARS-CoV-2 were both included. Participants retrospectively recorded their physical and mental symptoms, and completed EQ-5D-5L questionnaires during the acute phase, and at months 1, 3, and 6, which were compared between COVID-19 patients and test-negative controls. Additionally, the mean EQ-5D-5L utility score was compared between male and female COVID-19 patients.<br><br>RESULTS: A total of 302 COVID-19 patients and 77 test-negative controls were included (median age: 42 years; 41.2% male; 13.2% with underlying medical conditions). At month 3, 19.9% (60/302) of COVID-19 patients and 9.1% (7/77) of test-negative controls reported ongoing symptoms. Mental symptoms and fatigue persisted for over three months among COVID-19 patients. The mean EQ-5D-5L utility score during the acute phase for COVID-19 patients was 0.615 (95% confidence interval [CI]: 0.586-0.645), and 0.874 (95% CI: 0.826-0.921) for test-negative controls, with a mean difference of -0.258 (95% CI: -0.324 to -0.193). COVID-19 patients consistently exhibited lower EQ-5D-5L utility scores than controls for over six months post-infection. Female COVID-19 patients showed lower EQ-5D-5L utility scores compared to male patients throughout the period (acute phase mean difference: -0.091; 95% CI: -0.151 to -0.031).<br><br>CONCLUSIONS: COVID-19 patients experienced more symptoms three months post-testing compared to test-negative controls, with lower EQ-5D-5L utility scores persisting for over six months. Female COVID-19 patients exhibited lower EQ-5D-5L utility scores than their male counterparts throughout the period.},
}
@article {pmid40420038,
year = {2025},
author = {Vieira, YP and Camilo, LDS and Araújo, &#xc9;S and de Macedo Neto, JD and Junqueira, LL and Machado, KP and Gonzalez, TN and Neves, RG and Duro, SMS and Saes, MO},
title = {Inequalities in worsening work and income decrease/cessation in SARS-CoV-2 infection in adults and elderly people: the population-based SulCovid-19 study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {1946},
pmid = {40420038},
issn = {1471-2458},
mesh = {Humans ; *COVID-19/epidemiology/economics ; Female ; Male ; Cross-Sectional Studies ; Aged ; Middle Aged ; Brazil/epidemiology ; Adult ; *Income/statistics &amp; numerical data ; Socioeconomic Factors ; SARS-CoV-2 ; },
abstract = {OBJECTIVE: To evaluate inequalities in the worsening of work and income decrease/cessation among adults and elderly people with COVID-19 in the extreme south of Brazil.<br><br>METHODS: This is a cross-sectional study based on the SulCovid-19 study carried out with adults and elderly people infected with SARS CoV-2 from December/2020 to March/2021 in the municipality of Rio Grande, RS, Brazil. The outcomes were: "worsening of work" and "income decrease/cessation" following COVID-19. The independent variables were gender, skin color, income, education, health insurance, age, marital status, schooling, morbidities, hospitalization and long COVID.<br><br>RESULTS: prevalence of worsening work was 33.7% (95%CI 31.8; 35.5), while prevalence of income decrease/cessation was 44.6% (95%CI 42.7; 46.6). Female individuals with income in dollars between US0.00 and US192.0 had 13.0% (95% CI 1.01; 1.27) and 22.0% (95% CI 1.02; 1.46) greater prevalence of losing work and were 22.0% (95% CI 1.12; 1.34) and 49.0% (95% CI 1.31; 1.70) more likely to suffer a decrease/cessation of their income. Individuals with long COVID had 46.0% greater prevalence (95% CI 1.27; 1.68) of worsening at work and 24.0% (95% CI 1.13; 1.37) greater prevalence of income decrease/cessation when compared to those without the disease. Individuals with 3 symptoms or more had 86.0% (95% CI 1.58; 2.20) greater prevalence of worsening work and 47.0% (95% CI 1.31; 1.65) greater prevalence of income decrease/cessation when compared to those without long COVID symptoms.<br><br>CONCLUSIONS: There was inequality in the worsening of work and income decrease/cessation for individuals infected with SARS CoV-2. Among these individuals, females, lower income, low education and greater long COVID severity were the most affected.},
}
@article {pmid40417395,
year = {2025},
author = {Barros-Aragão, FGQ and Pinheiro, TL and Pinto, TP and Vanderborgh, B and Rezende, NBS and de Freitas, GB and de Freitas, GR and Bozza, FA and Souza, AS and Rodrigues, EC and Brandão, CO and Mattos, P and Sudo, FK and Tovar-Moll, FF and De Felice, FG},
title = {Comparison of cerebrospinal fluid biomarkers in patients with severe COVID-19 neurological outcomes and Alzheimer's disease.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {46},
number = {},
pages = {101007},
pmid = {40417395},
issn = {2666-3546},
abstract = {BACKGROUND: COVID-19 induces acute and long-term neurological symptoms. Links between COVID-19 neurological disturbance and Alzheimer's disease (AD) have been hypothesized because neuroinflammation plays a significant role in both diseases. However, it is unknown if COVID-19 patients with neurological disturbance present molecular alterations related to AD pathology. A better understanding of possible molecular links between COVID-19-induced neurological disease and AD would lead to improved patient follow-up and late-onset disease prevention. Here, we analyze early AD biomarkers in a Brazilian cohort of COVID-19 patients with neurological symptoms. We compared COVID-19 patients' neuroinflammatory and AD biomarker levels to controls, amnestic mild cognitive impairment (aMCI), and AD.<br><br>METHODS: We analyzed cerebrospinal (CSF) biomarkers of neuroinflammation (interleukin-6 (IL6)), amyloid-beta (A&#x3b2;) proteinopathy (A&#x3b2;42/40), phosphorylated Tau (pTau181), and the neurodegeneration-associated biomarker total Tau in controls (n&#xa0;=&#xa0;36), COVID-19 patients presenting neurological alterations (n&#xa0;=&#xa0;35), aMCI (n&#xa0;=&#xa0;19), and AD patients (n&#xa0;=&#xa0;20). Comparisons were corrected by possible sex, age, and comorbidities confounding effects. CSF biomarkers were correlated with systemic and neuro-inflammation markers.<br><br>RESULTS: We found that severe COVID-19 patients presented higher CSF Tau than controls, comparable to alterations observed in AD patients. However, we did not find changes in CSF A&#x3b2;42/40, pTau-181/A&#x3b2;42, or Tau/A&#x3b2;42 ratios. Severe COVID-19 patients presented higher Tau, Tau/A&#x3b2;42, and pTau181/A&#x3b2;42 than mild patients. In COVID-19 patients, CSF pro-inflammatory cytokine IL6 and AD biomarkers correlated with systemic inflammatory index (SII).<br><br>CONCLUSIONS: Collectively, our findings reveal that CSF tau levels are comparably elevated in COVID-19 neurological patients and AD, suggesting ongoing neurodegeneration in COVID-19 neurological disease, but no biomarker alterations related to AD pathology. Furthermore, CNS AD-related biomarker levels in COVID-19 patients change in association with disease severity and systemic inflammation. Considering that inflammation may persist post-COVID, our findings urge the assessment of possible AD-related biomarker changes in COVID-19 survivors with lingering symptoms.},
}
@article {pmid40416973,
year = {2025},
author = {Luo, Q and Song, Q and Li, Y and Zong, K and Liu, T and He, J and Mei, G and Du, H and Xia, Z and Liu, M and Song, J and Gao, C and Xia, D and Xue, G and Tian, W and Qu, Y and Kou, Z and Dong, Z and Han, J},
title = {Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1596065},
pmid = {40416973},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/virology ; Aged ; *SARS-CoV-2/immunology ; *Antibodies, Neutralizing/immunology/blood ; Female ; Male ; *Antibodies, Viral/immunology/blood ; Middle Aged ; Aged, 80 and over ; Immunologic Memory ; B-Lymphocytes/immunology ; Th17 Cells/immunology ; Memory B Cells/immunology ; },
abstract = {OBJECTIVES: To evaluate the immune persistence and cross-immune response of elderly individuals after Omicron BA.5 infections.<br><br>METHOD: The neutralizing antibodies against WT, BA.5, XBB.1 and EG.5 strains were analyzed. The T/B-cell subsets' responses were tested through intracellular cytokine staining and flow cytometry.<br><br>RESULTS: The neutralizing antibodies titers against WT and BA.5 strain, remaining high level for at least 6 months, were higher than that of both XBB.1 and EG.5 variants. The neutralizing antibodies of WT, BA.5, XBB.1, and EG.5 strains in the elderly were slightly lower than those in middle-age. The memory B cells decreased rapidly in the elderly, and Tfh, Th17 cells of the elderly continued to increase for only 3 months, while Tfh and Th17 cells increased in the middle-aged for over 6 months. For the elderly, after peptide stimulation, unswitched/switched memory B cells decreased, while double negative B cells displayed higher proliferation. The proportions of both na&#xef;ve and Temra cells in CD4[+] and CD8[+] T cells declined, whereas those of Tcm and Tem cells elevated. In the meantime, both CD69[+] and CD38[+] T cells decreased, but the frequencies of PD-1[+] and CTLA-4[+] of CD4[+] and CD8[+] T cells showed an increasing trend. The proportions of PD-1[+] and CTLA-4[+] cells also increased in older people with long COVID symptoms at 3m post-infection.<br><br>CONCLUSIONS: Omicron BA.5 infection induced lower neutralizing antibodies against XBB.1 and EG.5 variant. The decrease of memory B cells, CD69[+] and CD38[+]T cells, as well as the increase of PD-1[+], CTLA-4[+] of CD4[+]/CD8[+]T cells and double negative B cells, indicate that sustained immune responses against BA.5 infection may wane more rapidly in elderly populations.},
}
@article {pmid40416618,
year = {2025},
author = {Eltayeb, A and Adilović, M and Golzardi, M and Hromić-Jahjefendić, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM},
title = {Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19429},
pmid = {40416618},
issn = {2167-8359},
mesh = {Humans ; *COVID-19/complications ; *Thrombosis/virology/metabolism/etiology ; *SARS-CoV-2 ; *Coronavirus Nucleocapsid Proteins/metabolism ; },
abstract = {COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis-key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.},
}
@article {pmid40416333,
year = {2025},
author = {Beck, E and Joshi, K and Mehta, D and Lorenc, S and Rizkalla, B and Van de Velde, N},
title = {Workplace Vaccination Against COVID-19 and Seasonal Influenza in the United States: A Modeling-Based Estimation of the Health and Economic Benefits for Employers and Employees.},
journal = {Journal of market access &amp; health policy},
volume = {13},
number = {2},
pages = {17},
pmid = {40416333},
issn = {2001-6689},
abstract = {The objectives were to assess the economic burden of COVID-19 and impact of workplace COVID-19 vaccination in the United States (US). An economic model estimated COVID-19 workplace burden (infections, long COVID, inpatient/outpatient care, absent days) with and without vaccination, compared with seasonal influenza vaccination for context, using Optum's de-identified Clinformatics[®] Data Mart Database. Without workplace vaccination, an average US business (with 10,000 employees), had 18,175 absent days from COVID-19 and lost productivity costs of USD 5.08 million. Implementing COVID-19 workplace vaccination (at 70% coverage) prevented approximately 3132 absent days, saving employers USD 876,453 (lost productivity) and USD 240,633 (medical costs); and saving employees USD 182,196 (medical costs) and USD 198,250 (lost wages) versus no COVID-19 workplace vaccination. The burden and vaccination impact were greater for COVID-19 versus seasonal influenza. Workplace vaccination for COVID-19 and seasonal influenza can have a significant impact for both the employer and employees through averted disease.},
}
@article {pmid40416015,
year = {2025},
author = {Harabuchi, Y and Kumai, T and Nishi, K and Tanaka, A and Hotta, O and Hagino, H and Kusuyama, T and Mogitate, M and Ohno, Y and Sakakibara, A and Araki, S and Nishida, Y and Shintani, T and Takezawa, H and Ito, H and Komazawa, D and Nishiwaki, N and Toritani, R and Hirahata, K and Marumo, S},
title = {Retracted: Chronic Epipharyngitis Treated with Epipharyngeal Abrasion Therapy: Symptoms, Diagnosis, Pathogenesis, and Treatment Outcomes.},
journal = {JMA journal},
volume = {8},
number = {2},
pages = {371-384},
pmid = {40416015},
issn = {2433-3298},
abstract = {Chronic epipharyngitis is associated with a wide variety of symptoms, including local symptoms such as postnasal drip, sore throat, lump sensation of the pharynx, headache, chronic cough, nasal obstruction, tinnitus/ear fullness, chronic phlegm and dysphonia due to inflammation of the epipharynx, functional somatic symptoms such as chronic fatigue, dizziness, insomnia, brain fog, abdominal discomfort, and depression caused by dysfunction of the hypothalamus-limbic system via disturbances of vagal response and cerebrospinal fluid outflow, and distant organ symptoms such as immunoglobulin A nephropathy and palmoplantar pustulosis caused by the epipharyngeal lymphoid tissue as an etiologic organ. In the past, chronic inflammation in the epipharynx was difficult to prove by gross findings, now, direct observation of the epipharyngeal inflammation by endoscopy has become easier for the diagnosis. For the treatment of chronic epipharyngitis, epipharyngeal abrasive therapy (EAT), epipharyngeal application of a 1% zinc chloride solution intranasally or orally was popular since the 1960s, recently, endoscopic EAT (E-EAT), in which epipharynx is safely and accurately observed and abraded under clear vision using an endoscope, has been developed. The mechanisms of EAT effects can be classified into anti-inflammatory/antiviral effect, bloodletting effect, and vagus nerve stimulation effect. Recently, the effectiveness of EAT for post-acute sequelae of coronavirus disease 2019 (COVID-19), known as long COVID, has come into the limelight, and the number of patients for whom EAT is expected to increase. In 2019, the Japan Society of Stomato-pharyngology established the EAT Review Committee to accumulate evidence on the efficacy of EAT and to establish indications and techniques for its use. In this article, the EAT Review Committee outlines its symptoms, pathogenesis, and diagnosis of chronic epipharyngitis, technique of E-EAT, mechanisms of EAT effects, past reports for the efficacy of EAT, and a multicenter prospective study.},
}
@article {pmid40415285,
year = {2025},
author = {Eltayeb, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM},
title = {Intrinsic Factors Behind Long COVID: VI. Combined Impact of G3BPs and SARS-CoV-2 Nucleocapsid Protein on the Viral Persistence and Long COVID.},
journal = {Journal of cellular biochemistry},
volume = {126},
number = {5},
pages = {e70038},
doi = {10.1002/jcb.70038},
pmid = {40415285},
issn = {1097-4644},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/virology/metabolism/immunology/pathology ; *SARS-CoV-2/metabolism/physiology ; *Coronavirus Nucleocapsid Proteins/metabolism ; *RNA Recognition Motif Proteins/metabolism/immunology ; *Poly-ADP-Ribose Binding Proteins/metabolism/immunology ; *DNA Helicases/metabolism ; *Phosphoproteins/metabolism ; *RNA Helicases/metabolism ; Virus Replication ; Stress Granules/metabolism/virology ; Host-Pathogen Interactions ; },
abstract = {The efficient transmission of SARS-CoV-2 caused the COVID-19 pandemic, which affected millions of people around the globe. Despite extensive efforts, specific therapeutic interventions and preventive measures against COVID-19 and its consequences, such as long COVID, have not yet been identified due to the lack of a comprehensive knowledge of the SARS-CoV-2 biology. Therefore, a deeper understanding of the sophisticated strategies employed by SARS-CoV-2 to bypass the host antiviral defense systems is needed. One of these strategies is the inhibition of the Ras GTPase-activating protein-binding protein (GAP SH3-binding protein or G3BP)-dependent host immune response by the SARS-CoV-2 nucleocapsid (N) protein. This inhibition disrupts the formation of stress granules (SGs), which are crucial for antiviral defense. By preventing SG formation, the virus enhances its replication and evades the host's immune response, leading to increased disease severity. Given the involvement of G3BP1 in SG formation and its ability to interact with viral proteins, along with the crucial role of the N protein in the replication of the virus, we hypothesize that these proteins may have a potential role in the pathogenesis of long COVID. Despite the current lack of direct evidence linking these proteins to long COVID, their interactions and functions suggest a possible connection that warrants further investigation.},
}
@article {pmid40414164,
year = {2025},
author = {Keith, S and Hill, G and Smith, A and Brechin, D and Mustafa, R and Antunes, G and Swanson, V},
title = {Identifying the prevalence of symptoms of anxiety and depression in patients with post COVID.},
journal = {Journal of psychosomatic research},
volume = {194},
number = {},
pages = {112147},
doi = {10.1016/j.jpsychores.2025.112147},
pmid = {40414164},
issn = {1879-1360},
}
@article {pmid40413391,
year = {2025},
author = {Reis, N and Dias, MJC and Sousa, L and Oliveira, J and Rico, MT and Baixinho, CL and Henriques, MA},
title = {Respiratory telerehabilitation: user experience and satisfaction with the program.},
journal = {BMC geriatrics},
volume = {25},
number = {1},
pages = {372},
pmid = {40413391},
issn = {1471-2318},
mesh = {Humans ; Aged ; *Telerehabilitation ; Male ; Female ; *Pulmonary Disease, Chronic Obstructive/rehabilitation/psychology ; *Patient Satisfaction ; *COVID-19/epidemiology ; Aged, 80 and over ; Qualitative Research ; Portugal ; Telemedicine ; },
abstract = {BACKGROUND: The rise of telehealth in geriatric care is an inexorable movement toward adapting to global digitalization trends, in terms of both technology and implementation experiences, with clear gains for health systems and citizens. A literature review shows that the older population, with lower levels of digital literacy, faces specific challenges with this type of service. The aim of this study was to understand the way older people with Chronic Obstructive Pulmonary Disease or long COVID perceive the implementation of telerehabilitation programs to meet their healthcare needs.<br><br>METHODS: A qualitative study was conducted using semi-structured interviews to answer the research question: How do older people perceive telerehabilitation programs? The study participants were 17 people aged&#x2009;&#x2265;&#x2009;65 years old who had completed a respiratory telerehabilitation program at a Portuguese hospital. The interviews were submitted to content analysis using WebQDA[&#xae;] qualitative data analysis software.<br><br>RESULTS: The study participants had an average age of 70.94&#x2009;&#xb1;&#x2009;7.44 years old. The content of the interviews with these older people points to easy adaptation to the telerehabilitation program. Three categories and their respectives subcategories emerged from the content analysis: (1) access and continuity of care (access, continuity of care, and self-management); (2) presence (communication with the team and maintaining relationships); and (3) experience in the program (comfort, advantages, and difficulties).<br><br>CONCLUSIONS: This study allows for an understanding of how older people perceive participation in telerehabilitation programs, what they value, and the difficulties they experience. It makes it possible to make recommendations for clinic practice and research into this emerging area of health care.},
}
@article {pmid40412913,
year = {2025},
author = {DeMasi, M and Bujold, L},
title = {Effect of the Covid Pandemic on Women's Health.},
journal = {Primary care},
volume = {52},
number = {2},
pages = {371-382},
doi = {10.1016/j.pop.2025.01.009},
pmid = {40412913},
issn = {1558-299X},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Women's Health ; United States/epidemiology ; SARS-CoV-2 ; Pandemics ; },
abstract = {The corona virus disease 2019 (COVID-19) pandemic impacted all spheres of the lives of women. This article focuses on the impact on the health, careers, and family lives of women in the United States. There is a lasting impact from COVID-19 on the lives and health of women. Preventative care and chronic care were disrupted. Long covid seems to impact premenopausal women at much higher rates than men. Time spent between work and home changed for many during the pandemic. Women shifted to more time spent on home duties. The long-term outcome of career advancement and economic success is unknown.},
}
@article {pmid40412098,
year = {2025},
author = {Franco-Moreno, A and Torres-Macho, J},
title = {Long COVID.},
journal = {Medicina clinica},
volume = {165},
number = {2},
pages = {107009},
doi = {10.1016/j.medcli.2025.107009},
pmid = {40412098},
issn = {1578-8989},
}
@article {pmid40410115,
year = {2025},
author = {Tsai, TY and Kao, JH and Wei, SC},
title = {Reply to "Comment on "Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from Taiwan"".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2025.05.023},
pmid = {40410115},
issn = {0929-6646},
}
@article {pmid40408228,
year = {2025},
author = {Berwick, RJ and Sahbaie, P and Kenny, G and Guo, TZ and Neiland, H and Andersson, DA and Clark, JD and Mallon, P and Goebel, A},
title = {Postacute COVID-19 syndrome and fibromyalgia syndrome are associated with anti-satellite glial cell IgG serum autoantibodies but only fibromyalgia syndrome serum-IgG is pronociceptive.},
journal = {Pain},
volume = {166},
number = {10},
pages = {e397-e408},
pmid = {40408228},
issn = {1872-6623},
support = {PhD Fees//Pain Relief Foundation/ ; MR/S003428/1/MRF_/MRF_/United Kingdom ; 22976/VAC_/Versus Arthritis/United Kingdom ; 21544/VAC_/Versus Arthritis/United Kingdom ; MR/S003428/1/MRF_/MRF_/United Kingdom ; MR/S003428/1/MRC_/Medical Research Council/United Kingdom ; 21544/VAC_/Versus Arthritis/United Kingdom ; },
mesh = {*Fibromyalgia/immunology/blood ; Animals ; *Immunoglobulin G/blood/immunology ; *COVID-19/complications/immunology/blood ; Male ; Humans ; *Autoantibodies/blood/immunology ; Mice ; Female ; Middle Aged ; Mice, Inbred C57BL ; *Neuroglia/immunology ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; },
abstract = {Postacute COVID-19 syndrome (PACS) describes the persistence of symptoms following severe acute respiratory syndrome coronavirus 2 clearance. PACS is sometimes associated with pain and fatigue resembling fibromyalgia syndrome (FMS). Severe FMS has recently been associated with pronociceptive immunoglobulin G (IgG) autoantibodies and anti-satellite glial cell (SGC) IgG autoreactivity, suggesting an autoimmune aetiology. We validated FMS-IgG passive transfer and then tested the hypothesis that PACS-patients, with high musculoskeletal pain and fatigue, harbour proalgesic and anti-SGC autoantibodies. PACS-patients with high pain and fatigue or people recently recovered from acute COVID-19 were recruited to the All-Ireland Infectious Diseases Study. We pooled serum from 18 patients per group and purified their serum-IgG. In addition, we obtained IgG from UK patients with FMS and healthy controls to confirm assay performance. Passive transfer experiments of IgG (8 mg/d) over 3 days were conducted using male (C57BL/6J) mice (n = 6 mice per group). We measured mechanical and cold hypersensitivities and grip strength. Injection of FMS-IgG elicited the previously described mouse phenotype in male rodents, including increased mechanical/cold hypersensitivities and reduced grip strength compared with control IgG, whereas pooled PACS-IgG was inert. Immunocytochemistry of primary-SGC-enriched cultures reproduced the increased staining of FMS-IgG over the control reported previously. Both IgG from patients with PACS and those recently recovered from COVID-19 stained strongly positive. We confirm the pronociceptive properties of FMS-IgG and demonstrate, in contrast, that PACS symptoms from our cohort, with severe pain and fatigue, are not transmissible through passive transfer to male rodents. Postacute COVID-19 syndrome pain is often localised, and stratification according to the widespread distribution of pain should be considered for future studies; recovered COVID-19 leaves a strong trace of anti-SGC autoreactivity.},
}
@article {pmid40407658,
year = {2025},
author = {Park, SO and Nanda, N},
title = {Long COVID: A Systematic Review of Preventive Strategies.},
journal = {Infectious disease reports},
volume = {17},
number = {3},
pages = {},
pmid = {40407658},
issn = {2036-7430},
abstract = {Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking. Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms. Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC. Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID.},
}
@article {pmid40406601,
year = {2025},
author = {Lugo, ZR and Patiño-Torres, MJ},
title = {Editorial: Neuropsychiatric consequences of the COVID-19 pandemic: understanding mechanisms, risk factors, and treatment.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1611176},
pmid = {40406601},
issn = {1662-5161},
}
@article {pmid40406371,
year = {2025},
author = {Jacka, BP and Cheng, QL and Schiavone, B and Darley, DR and Kelleher, AD and Dore, GJ and Matthews, GV},
title = {Trajectories of Health-Related Quality of Life 2 Years After Mild/Moderate Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the Pre-Omicron Era.},
journal = {Open forum infectious diseases},
volume = {12},
number = {5},
pages = {ofaf142},
pmid = {40406371},
issn = {2328-8957},
abstract = {BACKGROUND: Individuals with postacute sequelae of coronavirus disease 2019 (COVID-19), or long COVID, experience substantial burden of illness many months after initial infection. Few studies have comprehensively and longitudinally assessed health outcomes for people with long COVID following mild/moderate infection. We applied the Wilson-Cleary model of health-related quality of life (HRQOL) to describe the impact of long COVID on multiple health dimensions up to 24 months following mild/moderate COVID-19.<br><br>METHODS: Participants within the ADAPT post-COVID study (N = 172, 86% mild/moderate infection) completed structured patient-reported outcome measures at 4, 8, 12, 18, and 24 months postinfection. Following the Wilson-Cleary model, questionnaires assessed symptoms (anxiety/depression, chronic fatigue, breathlessness), return to pre-COVID-19 functioning, perceived health status (EuroQol Visual Analogue Scale), and wellbeing (EuroQol EQ-5D-5L, Personal Wellbeing Index). Temporal trends were assessed using general estimating equations and ordinal logistic regression, including time &#xd7; long COVID interactions.<br><br>RESULTS: Thirty-seven percent of participants were diagnosed with long COVID (&#x2265;1 new/persisting symptoms of chest pain, breathlessness, or fatigue/malaise at least 12 weeks after infection). Long COVID was associated with poorer health outcomes across all domains at first assessment. Over 2 years, participants with long COVID reported improvement in return to pre-COVID-19 work and Somatic and Psychological Health Report chronic fatigue but sustained impairment was observed in all other health domains, compared to participants recovered from COVID-19.<br><br>CONCLUSIONS: Substantial long-term impairment in various health domains were observed for individuals with long COVID following mild/moderate initial infection, with little improvement over time in most. Multimodal interventions must address impairment in multiple domains of HRQOL in individuals with long COVID.},
}
@article {pmid40405092,
year = {2025},
author = {Seo, YB and Choi, YJ and Seo, JW and Kim, EJ and Lee, J and Song, JY},
title = {Therapeutic options for the treatment of post-acute sequelae of COVID-19: a scoping review.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {731},
pmid = {40405092},
issn = {1471-2334},
support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; },
mesh = {Humans ; Antiviral Agents/therapeutic use ; *COVID-19/complications/therapy ; *COVID-19 Drug Treatment ; Hyperbaric Oxygenation ; *Post-Acute COVID-19 Syndrome/therapy ; },
abstract = {OBJECTIVES: This scoping review aimed to summarize the available studies to address the question of which therapeutic agents can be utilized for patients with post-acute sequelae of COVID-19 (PASC).<br><br>METHODS: We conducted a systematic search in medical databases, including PubMed and Embase, for studies aligned with our objectives published between January 1, 2020, and July 22, 2024. For each study, we summarized the main symptoms targeted, study design, therapeutic regimens, evaluation tools, and clinical outcomes.<br><br>RESULTS: A total of 413 studies were identified, and 39 studies were included in this review based on relevance to the research objectives. We primarily focused on high-level evidence studies, such as meta-analyses and randomized controlled trials, but observational studies were included when evidence was scarce. Therapeutic agents evaluated included hyperbaric oxygen, ivermectin, metformin, naltrexone, micronutrient supplements, antifibrotic agents, antiviral agents, and selective serotonin reuptake inhibitors (SSRIs). Among these, hyperbaric oxygen, antifibrotic agents, antiviral agents, and SSRIs demonstrated promising results. However, the heterogeneity of PASC symptoms posed challenges in synthesizing findings for specific symptom-based outcomes.<br><br>CONCLUSION: Given the heterogeneity of symptoms, this review highlights the need for standardized and targeted research to better address the diverse therapeutic needs of patients with PASC.<br><br>CLINICAL TRIAL: Not applicable.},
}
@article {pmid40404198,
year = {2025},
author = {Puhan, MA and Dalla Lana, K},
title = {Rehabilitation for persons with long COVID beyond the recovery phase of SARS-CoV-2 infection.},
journal = {The European respiratory journal},
volume = {65},
number = {5},
pages = {},
doi = {10.1183/13993003.00239-2025},
pmid = {40404198},
issn = {1399-3003},
}
@article {pmid40404195,
year = {2025},
author = {Yonker, LM and Kane, B and Pretorius, E and Putrino, D and McFarland, S and Brodin, P and Zimmerman, KO and Munblit, D and Rowe, PC and Vos, T and Warburton, D and Stephenson, T and Buonsenso, D and , },
title = {Equity in research: a global consensus statement on the urgency of including children in long COVID clinical trials.},
journal = {The European respiratory journal},
volume = {65},
number = {5},
pages = {},
pmid = {40404195},
issn = {1399-3003},
support = {R01 HL173059/HL/NHLBI NIH HHS/United States ; },
abstract = {Efforts are urgently needed to intentionally address this inequity in long COVID research to include children early in clinical trial design. https://bit.ly/3RMGmYz},
}
@article {pmid40404020,
year = {2025},
author = {Schreiber, CS and Navarro Ramil, L and Bieligk, J and Meineke, R and Rimmelzwaan, G and Käufer, C and Richter, F},
title = {Intravenous SARS-CoV-2 Spike protein induces neuroinflammation and alpha-Synuclein accumulation in brain regions relevant to Parkinson's disease.},
journal = {Brain, behavior, and immunity},
volume = {129},
number = {},
pages = {102-123},
doi = {10.1016/j.bbi.2025.05.021},
pmid = {40404020},
issn = {1090-2139},
mesh = {Animals ; *alpha-Synuclein/metabolism ; *Spike Glycoprotein, Coronavirus/administration &amp; dosage/metabolism ; *Parkinson Disease/metabolism ; Male ; *Brain/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Female ; COVID-19/metabolism ; *Neuroinflammatory Diseases/metabolism ; SARS-CoV-2 ; Microglia/metabolism ; Administration, Intranasal ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) frequently presents with neurological symptoms in human patients and leads to long-lasting brain pathology in a hamster model. There is no overt SARS-CoV-2 virus replication in central neurons. Whether viral proteins are sufficient to cause this pathology requires further investigations. The SARS-CoV-2 Spike-protein S1-subunit (S1-protein) has recently gained interest for causing neuroinflammation and accelerating aggregation of alpha-Synuclein (aSyn) in vitro. Here, we show the impact of S1-protein in a broad spectrum of brain regions after injection via three different application routes in C57/BL6 mice.<br><br>METHODS: S1-protein was administered either intranasally, intravenously or intracerebrally. We quantified aSyn immunoreactivity and phosphorylated aSyn (pS129), microglia and astrocyte reactivity, ACE2/Neuropilin-1 receptor expression, and parvalbumin-positive interneurons in limbic system, basal ganglia, and cortical regions 14&#xa0;days post-application. Plasma cytokine profiles were assessed 6&#xa0;days post-injection.<br><br>RESULTS: While intracerebral injection resulted in decreased aSyn immunoreactivity with increased pS129 in males, intravenous injection led to increased levels of aSyn immunoreactivity and microglia cell density, predominantly in brain regions associated with Parkinson's disease pathology. Intranasal application of S1-protein induced microgliosis in some brain regions but resulted in sex-dependent alterations of aSyn levels, with increases in females and decreases in males. All routes showed sex-dependent alterations in astrocytic reactivity, receptor expression, and parvalbumin-positive interneurons.<br><br>CONCLUSION: Our results demonstrate that S1-protein itself leads to neuroinflammation, altered aSyn homeostasis, and disruption of inhibitory circuits in a route- and sex-dependent manner. These findings indicate the possibility of S1-protein being a crucial agent for both neuroinflammatory processes and altered protein regulation mechanisms. S1-protein trapped in tissue reservoirs could therefore explain symptoms occurring or persisting beyond viral clearance (Post COVID-19 condition).},
}
@article {pmid40403025,
year = {2025},
author = {Wander, PL and Lowy, E and Korpak, A and Beste, LA and Boyko, EJ},
title = {Association of long COVID documentation with clinical outcomes among Veterans with diabetes.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0324709},
pmid = {40403025},
issn = {1932-6203},
mesh = {Humans ; Female ; *COVID-19/epidemiology/complications/mortality ; Male ; *Veterans/statistics &amp; numerical data ; Aged ; Retrospective Studies ; United States/epidemiology ; *Diabetes Mellitus/epidemiology ; Middle Aged ; Glycated Hemoglobin ; Documentation ; Hypoglycemic Agents/therapeutic use ; Electronic Health Records ; SARS-CoV-2/isolation &amp; purification ; United States Department of Veterans Affairs ; Hospitalization/statistics &amp; numerical data ; },
abstract = {OBJECTIVE: To examine public health impacts of Long COVID on long-term hyperglycemia and metabolic health.<br><br>MATERIALS &amp; METHODS: We conducted a retrospective cohort study using US Veterans Health Administration electronic health records data to examine associations of Long COVID documentation (International Statistical Classification of Diseases, Tenth Revision code U09.9) with clinical outcomes (number of primary care visits, receipt of new classes of glucose-lowering medications, weight change, hemoglobin A1c, initiation of insulin, initiation of dialysis, hospitalization, and mortality) among U.S. Veterans with diabetes (1 October 2021-1 October 2023; n&#x2009;=&#x2009;1,896,080).<br><br>RESULTS: Veterans were 69.7 years old on average at cohort entry, 6% female, and 1% had U09.9 documentation. Compared to Veterans without U09.9, those with U09.9 had 39% more primary care visits per year after the index date (incidence rate ratio [IRR] 1.36, 95%CI 1.36; 1.37), 21% more glucose-lowering medication classes added per year (IRR 1.21, 95%CI 1.18; 1.24), a 0.62&#x2009;kg greater weight gain (95%CI 0.52; 0.72), a 0.10-point lower mean HbA1c (95%CI -0.12; -0.08), a 43% greater odds of starting insulin (odds ratio [OR] 1.43, 95%CI 1.32; 1.54), a 34% greater odds of starting dialysis (OR 1.34, 95%CI 1.11; 1.62), a 102% greater odds of VA hospitalization (OR 2.02, 95%CI 1.95; 2.09), and a 13% lower odds of mortality (OR 0.87, 95%CI 0.83; 0.91).<br><br>CONCLUSIONS: In Veterans with diabetes, Long COVID documentation was associated with greater medication use, odds of starting dialysis, and odds of hospitalization, but with lower odds of mortality. Individuals with Long COVID documentation did not have more weight gain or higher HbA1c, suggesting that adverse effects of Long COVID on medication changes and kidney function in persons with diabetes may be due to other factors. Future studies should examine mechanisms by which Long COVID might contribute to progression of kidney disease and more intensive diabetes treatment.},
}
@article {pmid40402473,
year = {2025},
author = {de Andrade, ML and do Monte, AL and Gerage, AM and Galliano, LM and Costa, EC and Ritti Dias, RM and Corrêa, FI},
title = {Effects of Physical Exercise on Functional Physical Performance in Individuals With Long COVID: A Systematic Review.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {45},
number = {4},
pages = {239-246},
pmid = {40402473},
issn = {1932-751X},
mesh = {Humans ; *COVID-19/rehabilitation/physiopathology/complications/psychology ; *Physical Functional Performance ; Quality of Life ; *Exercise Therapy/methods ; *Exercise/physiology ; SARS-CoV-2 ; Cardiorespiratory Fitness ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE: To analyze the effect of physical exercise on functional parameters in individuals with long coronavirus disease-2019 (COVID-19).<br><br>REVIEW METHODS: A search in MEDLINE, EMBASE, Web of Science, Scielo, and EBSCO was carried out in October 2022, and it was updated in June 2024. For inclusion, studies should have involved physical training without pulmonary rehabilitation, have involved individuals who had long COVID-19, and were prospective trials, clinical trials, or controlled trials. Two reviewers independently performed data extraction and assessed the risk of bias. Seven studies were reviewed, three of high methodological quality. Participants with long COVID-19 were hospitalized in two studies. Interventions lasted 2 to 16&#xa0;weeks, with frequencies of 2 to 7&#xa0;days per week, often involving resistance exercise. Strength improved in 67% of studies, cardiorespiratory fitness in 50%, and agility/mobility in 60%. Anxiety improved in 25% of studies, while depression improved in 75%. Quality of life improved across all studies, with dyspnea and fatigue improving in 40% and 80%, respectively.<br><br>SUMMARY: Results suggest potential benefits of exercise training for subjects with long COVID-19 in several outcomes, mainly in functional capacity, depression symptoms, quality of life, and fatigue.},
}
@article {pmid40400892,
year = {2025},
author = {Ferrer, G and Valerio-Pascua, F and Alas-Pineda, C and Gaitán-Zambrano, K and Pavón-Varela, DJ},
title = {Intranasal Chlorpheniramine for Early Symptomatic Treatment of COVID-19 and the Impact on Long-COVID.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82736},
pmid = {40400892},
issn = {2168-8184},
abstract = {This review explores the therapeutic potential of intranasal chlorpheniramine maleate (iCPM) in managing both acute COVID-19 and Long COVID by integrating histamine H1 receptor antagonism and bitter taste receptor (T2R) activation. Current literature on histamine-mediated inflammation, T2R activation, and the dual-action mechanisms of iCPM were analyzed. Emphasis was placed on its antiviral, anti-inflammatory, and mucosal immunity-enhancing properties. iCPM demonstrates significant efficacy in addressing acute COVID-19 symptoms by inhibiting histamine-mediated inflammatory pathways and reducing cytokine storms. As a T2R agonist, it enhances mucosal immunity through nitric oxide production, mucociliary clearance, and antimicrobial peptide synthesis, reducing viral replication and supporting respiratory health. Additionally, iCPM shows promise in mitigating persistent symptoms of long COVID, including fatigue, brain fog, and respiratory dysfunction, by addressing chronic inflammation and residual viral activity. The integration of H1 receptor antagonism and T2R activation positions iCPM as a novel dual-target therapy for respiratory infections. Its localized delivery and broad mechanism of action make it a promising candidate for managing both the acute and chronic phases of COVID-19. Future research should focus on large-scale clinical trials and personalized approaches based on genetic variations in T2R pathways.},
}
@article {pmid40400794,
year = {2025},
author = {Shah, N and Patel, D and Sousa, A and Leder, AN},
title = {Changes in Migraine Headaches Following SARS-CoV-2 Infection: A Case Series.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82708},
pmid = {40400794},
issn = {2168-8184},
abstract = {During the COVID-19 pandemic, changes in migraine headaches have been observed. This case series of seven patients seeks to identify changes in migraines following COVID-19 infection and discuss the mechanisms by which these changes may have occurred. The study was composed of seven subjects with prior COVID-19 infection and a preceding history of migraine disorder. Most of the subjects presented with increased frequency and intensity of migraines shortly or immediately following COVID-19 infection. Many also described a shift in pain from local to diffuse headache. Additionally, some subjects developed other neuropsychiatric symptoms consistent with long COVID that included brain fog and, unusually, aphasia. After COVID-19 infection, six subjects had reduced efficacy for their medications and had to alter their regimen. Standard treatments such as Botox and anti-calcitonin gene-related peptide (anti-GCRP) had varied success among the cases. It is important to note that the pathophysiology of migraines during COVID-19 is still unclear and other factors can play a role. Nevertheless, individuals with a history of migraines noticed worsening symptoms and changes in medication efficacy following COVID-19 infection.},
}
@article {pmid40399555,
year = {2025},
author = {Lammi, V and Nakanishi, T and Jones, SE and Andrews, SJ and Karjalainen, J and Cortés, B and O'Brien, HE and Ochoa-Guzman, A and Fulton-Howard, BE and Broberg, M and Haapaniemi, HH and Kanai, M and Pirinen, M and Schmidt, A and Mitchell, RE and Mousas, A and Mangino, M and Huerta-Chagoya, A and Sinnott-Armstrong, N and Cirulli, ET and Vaudel, M and Kwong, ASF and Maiti, AK and Marttila, MM and Posner, DC and Rodriguez, AA and Batini, C and Minnai, F and Dearman, AR and Warmerdam, CAR and Sequeros, CB and Winkler, TW and Jordan, DM and Rešcenko, R and Miano, L and Lane, JM and Chung, RK and Guillen-Guio, B and Leavy, OC and Carvajal-Silva, L and Aguilar-Valdés, K and Frangione, E and Guare, L and Vergasova, E and Marouli, E and Striano, P and Zainulabid, UA and Kumar, A and Ahmad, HF and Edahiro, R and Azekawa, S and , and , and , and , and , and , and , and , and , and Luoh, SW and Erikstrup, C and Pedersen, OBV and Lerner-Ellis, J and Colombo, A and Grzymski, JJ and Ishii, M and Okada, Y and Beckmann, ND and Kumari, M and Wagner, R and Heid, IM and John, C and Short, PJ and Magnus, P and Ansone, L and Valenti, LVC and Lee, SA and Wain, LV and Verdugo, RA and Banasik, K and Geller, F and Franke, LH and Rakitko, A and Duncan, EL and Renieri, A and Tsilidis, KK and de Cid, R and Niavarani, A and Abner, E and Tusié-Luna, T and Verma, SS and Smith, GD and Timpson, NJ and Madduri, RK and Cho, K and Daly, MJ and Ganna, A and Schulte, EC and Richards, JB and Ludwig, KU and Marks-Hultström, M and Zeberg, H and Ollila, HM},
title = {Genome-wide association study of long COVID.},
journal = {Nature genetics},
volume = {57},
number = {6},
pages = {1402-1417},
pmid = {40399555},
issn = {1546-1718},
support = {S10 OD026880/OD/NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 AI159260/AI/NIAID NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; R01 AI170850/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study ; *COVID-19/genetics ; SARS-CoV-2 ; *Forkhead Transcription Factors/genetics ; Polymorphism, Single Nucleotide ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Pandemics ; Middle Aged ; *Pneumonia, Viral/genetics ; Post-Acute COVID-19 Syndrome ; },
abstract = {Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.},
}
@article {pmid40397934,
year = {2025},
author = {Khakban, I and Jain, S and Gallab, J and Dharmaraj, B and Zhou, F and Lokker, C and Abdelkader, W and Zeraatkar, D and Busse, JW},
title = {Impact of the COVID-19 Pandemic and the 2021 National Institute for Health and Care Excellence Guidelines on Public Perspectives Toward Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Thematic and Sentiment Analysis on Twitter (Rebranded as X).},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e65087},
pmid = {40397934},
issn = {1438-8871},
mesh = {*COVID-19/epidemiology ; *Fatigue Syndrome, Chronic/therapy/psychology/diagnosis ; Humans ; *Social Media ; United Kingdom/epidemiology ; SARS-CoV-2 ; Pandemics ; Practice Guidelines as Topic ; *Public Opinion ; },
abstract = {BACKGROUND: Myalgic encephalomyelitis (ME), also referred to as chronic fatigue syndrome (CFS), is a complex illness that typically presents with disabling fatigue and cognitive and functional impairment. The etiology and management of ME/CFS remain contentious and patients often describe their experiences through social media.<br><br>OBJECTIVE: We explored public discourse on Twitter (rebranded as X) to understand the concerns and priorities of individuals living with ME/CFS, with a focus on (1) the COVID-19 pandemic and (2) publication of the 2021 UK National Institute for Health and Care Excellence (NICE) guidelines on the diagnosis and management of ME/CFS.<br><br>METHODS: We used the Twitter application programming interface to collect tweets related to ME/CFS posted between January 1, 2010, and January 30, 2024. Tweets were sorted into 3 chronological periods (pre-COVID-19 pandemic, post-COVID-19 pandemic, and post-UK 2021 NICE Guidelines publication). A Robustly Optimized Bidirectional Embedding Representations from Transformers Pretraining Approach (RoBERTa) language processing model was used to categorize the sentiment of tweets as positive, negative, or neutral. We identified tweets that mentioned COVID-19, the UK NICE guidelines, and key themes identified through latent Dirichlet allocation (ie, fibromyalgia, research, and treatment). We sampled 1000 random tweets from each theme to identify subthemes and representative quotes.<br><br>RESULTS: We retrieved 906,404 tweets, of which 427,824 (47.2%) were neutral, 369,371 (40.75%) were negative, and 109,209 (12.05%) were positive. Over time, both the proportion of negative and positive tweets increased, and the proportion of neutral tweets decreased (P<.001 for all changes). Tweets mentioning fibromyalgia acknowledged similarities with ME/CFS, stigmatization associated with both disorders, and lack of effective treatments. Treatment-related tweets often described frustration with ME/CFS labeled as mental illness, dismissal of concerns by health care providers, and the need to seek out "good physicians" who viewed ME/CFS as a physical disorder. Tweets on research typically praised studies of biomarkers and biomedical therapies, called for greater investment in biomedical research, and expressed frustration with studies suggesting a biopsychosocial etiology for ME/CFS or supporting management with psychotherapy or graduated activity. Tweets about the UK NICE guidelines expressed frustration with the 2007 version that recommended cognitive behavioral therapy and graded exercise therapy, and a prolonged campaign by advocacy organizations to influence subsequent versions. Tweets showed high acceptance of the 2021 UK NICE guidelines, which were seen to validate ME/CFS as a biomedical disease and recommended against graded exercise therapy. Tweets about COVID-19 often noted overlaps between post-COVID-19 condition and ME/CFS, including claims of a common biological pathway, and advised there was no cure for either condition.<br><br>CONCLUSIONS: Our findings suggest research is needed to inform how best to support patients' engagement with evidence-based care. Furthermore, while patient involvement with ME/CFS research is critical, unmanaged intellectual conflicts of interest may threaten the trustworthiness of research efforts.},
}
@article {pmid40395923,
year = {2025},
author = {Nagase, M and Takeshita, Y and Tomooka, K},
title = {Treatment Strategy for Long COVID Based on Traditional Chinese Medicine.},
journal = {Juntendo medical journal},
volume = {71},
number = {2},
pages = {102-105},
pmid = {40395923},
issn = {2759-7504},
abstract = {Post-acute COVID-19 conditions, commonly known as 'long COVID', occur in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection, typically 3 months from the onset of COVID-19 with symptoms, lasting for at least 2 months, that cannot be explained by any alternative diagnoses. Although most symptoms improve over time, some patients experience significant limitations in their social lives. Under such circumstances, complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. There are a wide variety of CAM interventions, such as traditional Japanese medicine (Kampo medicine) and traditional Chinese medicine (TCM). In this study, we compared three studies using Kampo medicine with those using TCM and concluded that Kampo medicine, which is often practiced in Japan due to its historical background, may have some limitations in managing the diverse symptoms of long COVID because the symptoms of long COVID vary widely. Therefore, we propose that medical examinations based on TCM should also be considered as an alternative treatment strategy for patients with long COVID.},
}
@article {pmid40393269,
year = {2025},
author = {Struhal, W and Almamoori, D},
title = {A review of the sequelae of post Covid-19 with neurological implications (post-viral syndrome).},
journal = {Journal of the neurological sciences},
volume = {474},
number = {},
pages = {123532},
doi = {10.1016/j.jns.2025.123532},
pmid = {40393269},
issn = {1878-5883},
mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/etiology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Post Covid-19 conditions represent a medical challenge; a unified definition is not achieved after 5 years of the Pandemic. The incidence of Post Covid-19 conditions varies, nevertheless the neurological complications represent an important aspect in the spectrums of fields involved. The current perception is that varied manifestations and long-term complications of COVID-19 reflect underlying pathophysiological processes, including inflammatory, immune-mediated, and vascular mechanisms. These mechanisms underscore the complexity of COVID-19's impact including the nervous system and its potential for lasting effects. A number of symptoms are extremely severe and may also need neurologic attention including fatigue, cognitive disturbances, autonomic symptoms, headache, and sleep disorders. Post Covid-19 conditions are often of chronic nature. Management as in other chronic conditions should rely on the conventional diagnostic measures and management of symptoms irrespective of the temporal relation to the viral infection. To date Post Covid-19 conditions is only accepted as an additional or explanatory diagnosis.},
}
@article {pmid40393061,
year = {2025},
author = {Junainah, EM and Abd-El-Rahman, AH and Alamin, AA and Hassan, KE and Elesawy, BH and Elrashidy, AH and Alhosary, AA and Tufail-Chaudhary, H and El-Kenawy, AE and Bashir, AF and Obaid-Alnefaie, G and Nemenqani, DM and El-Nashar, NA and Khairy, M and Al-Thobaiti, NA and Alfahmi, FK and Taha, SA},
title = {Immunopathology and therapeutic strategies for long COVID: mechanisms, manifestations, and clinical implications.},
journal = {AIDS reviews},
volume = {27},
number = {1},
pages = {25-32},
doi = {10.24875/AIDSRev.24000018},
pmid = {40393061},
issn = {1698-6997},
mesh = {Humans ; *COVID-19/immunology/complications/therapy ; Middle Aged ; Adult ; Male ; SARS-CoV-2 ; Longitudinal Studies ; Aged ; Female ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Adolescent ; Young Adult ; Autoantibodies/blood ; Inflammation/immunology ; Interleukin-6/blood ; },
abstract = {Long coronavirus disease-19 (COVID-19) is a complex, multifactorial condition characterized by persistent symptoms lasting more than 12 weeks following acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The underlying mechanisms remain incompletely understood, but chronic inflammation, immune dysregulation, autoimmunity, and viral persistence are increasingly being implicated. This study investigated the immunopathological drivers of long COVID-19 and their associations with clinical manifestations and organ damage. A prospective, longitudinal cohort study was conducted on 200 COVID-19 survivors aged 18-65 years, in which immune markers, autoantibody profiles, lymphocyte dysfunction, and imaging findings were assessed over a 12-month period. Persistent inflammation was observed, with elevated interleukin-6 and tumor necrosis factor α ± levels correlated with lung fibrosis and cognitive impairment. Autoantibodies were detected in 40% of the participants, particularly those with cardiovascular and neurological symptoms. A significant reduction in CD8+ T-cell counts was associated with severe fatigue and cognitive dysfunction, whereas persistent SARS-CoV-2 RNA was identified in 10% of cases, primarily in individuals with gastrointestinal symptoms. Imaging studies revealed multiorgan involvement, with structural abnormalities in the lungs, heart, and brain. These findings highlight the interplay of immune dysfunction, chronic inflammation, and autoimmunity in long-term COVID-19, underscoring the need for targeted therapeutic strategies to address its long-term health impacts.},
}
@article {pmid40393039,
year = {2025},
author = {Carr, CR and Gentile, NL and Bertolli, J and Szewczyk, W and Lin, JS and Unger, ER and Vu, QM and Sotoodehnia, N and Fitzpatrick, AL},
title = {Comparison of long COVID, recovered COVID, and non-COVID Post-Acute Infection Syndromes over three years.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0323104},
pmid = {40393039},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/diagnosis/virology ; Female ; Male ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2/isolation &amp; purification ; Adult ; Electronic Health Records ; },
abstract = {BACKGROUND: Comparing the characteristics of patients with long COVID to those with other post-acute infection syndromes (PAIS) could potentially provide clues to common underlying disease processes that may affect patient recovery.<br><br>METHODS: We identified records of patients who had documented SARS-CoV-2 tests in the University of Washington Medicine electronic health record (EHR) database from January 1, 2019, through January 31, 2022 (n&#x2009;=&#x2009;139,472). Patients were classified into three groups: 1) long COVID defined by a positive SARS-CoV-2 test and a long COVID-related diagnosis code (n&#x2009;=&#x2009;580); 2) recovered COVID defined by a positive test and no long COVID associated diagnosis codes (n&#x2009;=&#x2009;7,437); and 3) non-COVID PAIS defined by a negative test, non-SARS-CoV-2 related PAIS diagnosis codes, and no COVID related codes (n&#x2009;=&#x2009;106). Using multivariate logistic regression, we compared the clinical characteristics of these groups at three timeframes to address preclinical, acute and post-acute diagnoses: before index SARS-CoV-2 test, within 30 days of index test, and&#x2009;>&#x2009;30 days after index test.<br><br>RESULTS: The long COVID group had a higher Charlson comorbidity index [median (IQR), 2 (0-4)] than the other two patient groups [median (IQR), 1 (0-3) and 1 (0-3)]. The long COVID and non-COVID PAIS patients were older and had greater smoking exposure than the recovered COVID group. Compared to the recovered COVID control group, the long COVID group had more health problems prior to the infection, including respiratory and metabolic as well as more severe infections and comorbidities based on the ICD codes found in the acute phase records. In the post-acute timeframe, many symptoms were more likely to be associated with long COVID than recovered patients with COVID-19 including abnormalities of heart beat [OR (95% CI), 5.31 (3.96-7.13)], cognition, perception, or emotional state symptoms [OR (95% CI), 5.14 (3.81-6.92)], malaise and fatigue [OR (95% CI), 4.20 (3.13-5.63)], and sleep disorders [OR (95% CI), 2.47, (1.79-3.43)], all p&#x2009;<&#x2009;0.05. In contrast, the non-COVID PAIS group shared many similarities with the long COVID group across all three timeframes.<br><br>CONCLUSIONS: Patients diagnosed with long COVID were more similar to patients with a non-COVID-related PAIS than to recovered patients with COVID-19. This suggests risk factors for PAIS may be similar and independent of the infectious agent.},
}
@article {pmid40392206,
year = {2025},
author = {Hery, CM and Zhang, X and McLaughlin, E and Von Ah, D and Anderson, GL and Harris, HR and VoPham, T and Garcia, L and Shadyab, AH and Follis, S and Paskett, ED},
title = {Association of Cancer History with COVID-19 Risk and Outcomes among Older Postmenopausal Women: Results from the Women's Health Initiative.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {34},
number = {8},
pages = {1286-1294},
pmid = {40392206},
issn = {1538-7755},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; K00 CA253745/CA/NCI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Female ; *COVID-19/epidemiology/virology ; Aged ; *Postmenopause ; Middle Aged ; Risk Factors ; *Neoplasms/epidemiology ; Women's Health ; Prospective Studies ; SARS-CoV-2/isolation &amp; purification ; United States/epidemiology ; },
abstract = {BACKGROUND: Several studies early in the COVID-19 pandemic suggested that those with a cancer history had a higher risk of COVID-19 infections and complications. However, few prospective studies evaluated the association of cancer with COVID-19 in older women. We aimed to examine the association of cancer history with the risk of COVID-19 and various COVID-19 outcomes among older women.<br><br>METHODS: The Women's Health Initiative is an ongoing cohort study that recruited 161,808 postmenopausal women of 50 to 79 years of age from 1993 to 1998. Those who completed the COVID-19 survey (2021-2022) were included (n = 35,623). Multivariable linear and logistic regressions were used to examine COVID-19 positivity, symptom severity, long COVID, and COVID concerns/anxiety outcomes.<br><br>RESULTS: Twenty-eight percent (n = 9,901) of participants had a history of cancer. Cancer history was not significantly associated with COVID-19 positivity [OR = 0.94; 95% confidence interval (CI), 0.81-1.08], COVID-19 hospitalization (OR = 1.21; 95% CI, 0.85-1.72), number of symptoms (least squares mean = 0.33; 95% CI, -0.20 to 0.85), and long COVID (OR = 1.18; 95% CI, 0.88-1.58).<br><br>CONCLUSIONS: A history of cancer was not associated with most COVID-19 outcomes. Future studies should continue to examine physiologic mechanisms contributing to differences among cancer survivors and prioritize the inclusion of underserved populations to identify strategies to address the impact of COVID-19.<br><br>IMPACT: These findings may assure cancer survivors that their diagnosis alone does not increase their risk of COVID-19 and suggest that older women with a history of cancer may have similar risks of COVID-19 outcomes compared with their noncancer counterparts.},
}
@article {pmid40391677,
year = {2025},
author = {Silver, SR and Li, J and Saydah, SH},
title = {Burden of Selected Chronic Conditions Among Adults of Prime Working Age (25-54) by 2022 Self-Reported COVID-19 and Long COVID History Compared to 2019 Pre-Pandemic Baseline Prevalence: Behavioral Risk Factor Surveillance System.},
journal = {American journal of industrial medicine},
volume = {68},
number = {7},
pages = {620-630},
doi = {10.1002/ajim.23735},
pmid = {40391677},
issn = {1097-0274},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/epidemiology ; Adult ; Middle Aged ; Behavioral Risk Factor Surveillance System ; Chronic Disease/epidemiology ; Male ; Female ; Prevalence ; Self Report ; SARS-CoV-2 ; United States/epidemiology ; *Employment/statistics &amp; numerical data ; *Cost of Illness ; Asthma/epidemiology ; Diabetes Mellitus/epidemiology ; },
abstract = {INTRODUCTION: Prior research has observed increased risks for numerous chronic conditions among individuals with Long COVID. Chronic conditions have been associated with employment limitations and increased economic hardships. Data from the Behavioral Risk Factor Surveillance System (BRFSS) present an opportunity to examine changes by employment status in the prevalence of a range of chronic conditions between 2019 (pre-pandemic) and, in 2022, by self-reported COVID-19 or Long COVID.<br><br>METHODS: We assessed the prevalence of chronic conditions in 2022 by employment status and self-reported COVID-19 and Long COVID history using data from BRFSS for adults of prime working age (25-54 years) who were employed for wages, self-employed, unemployed less than 1 year, unemployed 1 year or more, or unable to work. For each chronic condition (coronary heart disease and myocardial infarction [combined], stroke, ever and current asthma, chronic obstructive pulmonary disease, kidney disease, diabetes, and arthritis), we generated adjusted prevalence ratios (aPRs) comparing 2022 prevalence by COVID-19/Long COVID category to prevalences among respondents in that employment status before the pandemic (2019).<br><br>RESULTS: The prevalence of both asthma and diabetes increased significantly between 2019 and 2022 among respondents in all included employment categories and COVID-19/Long COVID histories combined. Among employed respondents with Long COVID in 2022, aPRs using 2019 prevalence figures for all employed respondents as a baseline for comparison had statistically significant elevations for every chronic condition assessed.<br><br>CONCLUSIONS: The increased prevalence of a range of chronic conditions between 2019 and 2022 among adults with Long COVID may present a burden for individuals, the workplace, the healthcare system, and the economy. Additional research in a longitudinal context could better quantify these associations. Efforts to prevent, identify, and treat Long COVID can reduce this burden.},
}
@article {pmid40391100,
year = {2025},
author = {Dassaye, R and Chetty, T and Daniels, B and Ramraj, T and Gaffoor, Z and Spooner, E and Mthethwa, N and Nsibande, DF and Magasana, V and Mohlabi, K and Singini, I and Gwebushe, N and Woeber, K and Goga, A},
title = {SARS-CoV-2 seroprevalence among learners in grades 1-7, their parents and teachers in KwaZulu-Natal, South Africa: a cross-sectional study.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1548945},
pmid = {40391100},
issn = {2296-2565},
mesh = {Humans ; South Africa/epidemiology ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Seroepidemiologic Studies ; Male ; Female ; *Parents ; *School Teachers/statistics &amp; numerical data ; Child ; *SARS-CoV-2/immunology ; Adolescent ; Adult ; *Students/statistics &amp; numerical data ; Schools ; Prevalence ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: There is limited information on SARS-CoV-2 seroprevalence among children and adolescents in LMIC school settings. We aimed to assess (1) the seroprevalence of SARS-CoV-2 antibodies, (2) prevalence of self-reported or confirmed SARS-CoV-2 prior infections and, (3) COVID-19 symptoms (including long-COVID) among a cohort of primary school learners, their parents and teachers in a semi-rural school setting approximately 3-years into the COVID-19 pandemic.<br><br>METHODS: Learners in grades 1-7 attending two pre-selected schools in close proximity in the Ndwedwe area, iLembe district, KwaZulu-Natal, South Africa, their parents and teachers were invited to enroll into the COVID Kids Schools Study (CoKiDSS) - a cross-sectional survey conducted between May-August 2023. All participants provided informed consent, completed a questionnaire and provided a fingerprick of blood for SARS-CoV-2 antibody testing using the COVID-19 IgG/IgM Rapid Test. Statistical methods included descriptive analysis, jackknife-estimated seroprevalence and incidence (unadjusted and sensitivity-adjusted), and logistic regression using generalized linear models.<br><br>RESULTS: A total of 645 participants (i.e., 456 learners, 147 parents and 42 teachers) were enrolled into the survey. Overall SARS-CoV-2 IgG seroprevalence was 78% unadjusted to 81% adjusted with an increasing seropositivity trend, from learners to teachers (76% unadjusted to 79% adjusted in learners, 79% unadjusted to 82% adjusted in parents and 93% unadjusted to 97% adjusted in teachers). About 2.6% of learners tested IgM seropositive. Interestingly, 17% of the participants, including 20% learners, tested negative for SARS-CoV-2 antibodies. While only 16 participants (2.5% - 2 learners, 10 parents, and four teachers) self-reported a prior confirmed SARS-CoV-2 infection. Of these 2 learners (100%), eight parents (80%) and 4 teachers (100%) reported COVID-19 like symptoms that persisted for &#x2265;28-days.<br><br>CONCLUSION: We reported high SARS-CoV-2 IgG seroprevalence among learners in grades 1-7, their parents and teacher approximately 3&#x202f;years into the COVID-19 pandemic which may be attributed to the snowball effect of multiple waves of infection in South Africa. However, only a small proportion of participants self-reported prior COVID-19 infection. This may be due to (1) recall bias and participants' perception of low susceptibility to and severity of COVID-19, (2) limited access to SARS-CoV-2 testing, and/or (3) a high prevalence of asymptomatic infections.},
}
@article {pmid40391044,
year = {2025},
author = {Duenas, K and Chwa, WJ and Hoque, F},
title = {Overview of Long COVID: Navigating the Aftermath.},
journal = {Journal of Brown hospital medicine},
volume = {4},
number = {2},
pages = {133879},
pmid = {40391044},
issn = {2994-5593},
abstract = {The coronavirus disease (COVID-19) pandemic was a global health crisis with far-reaching consequences. Among these were physical and mental health complications that emerged weeks or even months after the initial COVID-19 infection, collectively termed "long COVID" or "post-COVID syndrome." Identifying the epidemiology, risk factors, clinical manifestations, and management strategies for long COVID is crucial for both clinicians and patients, which is the focus of this review. The prevalence of long COVID varies across studies, generally ranging from 5% to 20%. Prominent risk factors include female sex, older age, a high number of acute symptoms, lower socioeconomic status, and underlying comorbidities such as diabetes, asthma, or chronic obstructive pulmonary disease. The clinical manifestations of long COVID are diverse; beyond the commonly reported symptoms of fatigue, malaise, ageusia, and anosmia, neuropsychiatric complications such as headache, cognitive deficits, and depression are also potential outcomes. Although there is currently no consensus on the management of long COVID, multidisciplinary care teams with appropriate referrals and follow-up diagnostic studies are essential in evaluating the clinical course of long COVID patients.},
}
@article {pmid40390477,
year = {2025},
author = {Finsterer, J},
title = {The Spectrum of Long-COVID Symptoms Should Be Assessed Through On-Site Examinations Rather Than Electronic Questionnaires.},
journal = {The American journal of medicine},
volume = {138},
number = {6},
pages = {e119},
doi = {10.1016/j.amjmed.2024.06.017},
pmid = {40390477},
issn = {1555-7162},
}
@article {pmid40390475,
year = {2025},
author = {Finsterer, J},
title = {If Internal Tremor and Vibrations in Long-COVID Cannot Be Confirmed by Abnormal Instrumental Examinations, Psychiatrists are Required.},
journal = {The American journal of medicine},
volume = {138},
number = {6},
pages = {e117},
doi = {10.1016/j.amjmed.2024.07.032},
pmid = {40390475},
issn = {1555-7162},
}
@article {pmid40389117,
year = {2025},
author = {Rudroff, T},
title = {Climate crossroads: How global warming drives coronavirus emergence, the long COVID crisis of tomorrow, and AI's role in navigating our future.},
journal = {Infectious diseases now},
volume = {55},
number = {6},
pages = {105091},
doi = {10.1016/j.idnow.2025.105091},
pmid = {40389117},
issn = {2666-9919},
mesh = {Humans ; *COVID-19/epidemiology/transmission/virology ; *Global Warming ; SARS-CoV-2 ; Animals ; *Artificial Intelligence ; Climate Change ; Pandemics ; *Coronavirus Infections/epidemiology/transmission ; },
abstract = {This narrative review examines the critical nexus between climate change, coronavirus emergence, and Long COVID-a triad that may shape public health outcomes for generations. Climate change disrupts ecological balances that have historically limited viral spillover events, creating novel interfaces between wildlife reservoirs and human populations. The coronavirus family presents particular concern due to its diversity, adaptability, and demonstrated capacity for cross-species transmission. With over 200 coronaviruses identified in bat populations alone, this vast reservoir of genetic diversity, combined with the family's propensity for recombination, creates substantial pandemic potential that climate disruption may further amplify. Long COVID has revealed another dimension of the coronavirus threat: the potential for significant chronic disease burden following acute infection. This complex multisystem condition affects a substantial portion of SARS-CoV-2 infected individuals, with mechanisms including viral persistence, autoimmunity, microclot formation, and mitochondrial dysfunction. Future projections suggest that climate change could increase global viral spillover risk by 30-45% by 2070, particularly in Southeast Asia, Central Africa, and parts of South America. Artificial intelligence offers promising tools for addressing these interconnected challenges through enhanced surveillance, accelerated therapeutic development, and optimized healthcare delivery. Understanding the climate-coronavirus-chronic illness nexus has become essential to the development of resilient health systems and effective planetary health policies face to an uncertain future.},
}
@article {pmid40387694,
year = {2026},
author = {Weix, NM and Shake, HM and Duran Saavedra, AF and Clingan, HE and Hernandez, VC and Johnson, GM and Hansen, AD and Collins, DM and Pryor, LE and Kitchens, R and Armstead, A and Hilton, C},
title = {Cognitive Interventions and Rehabilitation to Address Long-COVID Symptoms: A Systematic Review.},
journal = {OTJR : occupation, participation and health},
volume = {46},
number = {1},
pages = {74-95},
pmid = {40387694},
issn = {1938-2383},
mesh = {Humans ; *COVID-19/rehabilitation/complications/psychology ; *Cognitive Behavioral Therapy/methods ; *Occupational Therapy/methods ; SARS-CoV-2 ; *Cognitive Dysfunction/rehabilitation ; Quality of Life ; },
abstract = {Long COVID symptoms include cognitive and physical deficits impacting one's functional performance and quality of life. Limited evidence examines the use of cognitive interventions provided by occupational therapists in treating long COVID symptoms among adults. This systematic review summarizes existing studies on cognitive interventions and rehabilitation to treat long COVID symptoms and discusses their potential use within the scope of occupational therapy practice. We identified literature from 2021 to 2023 through searches of MEDLINE, CINAHL, PsycINFO, Cochrane Trials, and Scopus databases. Nineteen articles met inclusion criteria and were categorized into five types of intervention: (a) cognitive training, (b) cognitive behavioral therapy, (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multi-component rehabilitation programs. Strong evidence supports cognitive training, moderate supports cognitive behavioral training and low-level evidence supports other interventions provided by occupational therapists to target long COVID cognitive symptoms in adults.},
}
@article {pmid40387234,
year = {2025},
author = {Silva, L and Fernandes, J and Lopes, R and Costa, S and Malheiro, S and Aires, E and Pereira, D and Fonte, J and Dias, A and Oliveira, V and Cavaco, S and Magalhães, R and Correia, M and Andrade, C and Maia, LF},
title = {Long-Term Persistent Headache After SARS-CoV-2 Infection: A Follow-Up Population-Based Study.},
journal = {European journal of neurology},
volume = {32},
number = {5},
pages = {e70130},
pmid = {40387234},
issn = {1468-1331},
support = {//Bial Foundation/ ; //Foundation for Science and Technology/ ; },
mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Middle Aged ; Male ; Adult ; Follow-Up Studies ; *Headache/epidemiology/etiology ; Prospective Studies ; Aged ; Incidence ; Migraine Disorders/epidemiology ; },
abstract = {BACKGROUND: Headache is a symptom of the long-COVID syndrome. The incidence and characteristics of de novo post-COVID headaches remain unclear. Our aim was to characterize new-onset headaches in a population-based prospective cohort of COVID-19 patients from the first pandemic wave.<br><br>METHODS: This study followed a prospective cohort of 732 COVID-19 patients consecutively diagnosed between March and June 2020. Neurological follow-up was performed face-to-face or by phone at 3, 12, and 24&#x2009;months. A structured clinical questionnaire was used to characterize headaches before infection and 24&#x2009;months postinfection.<br><br>RESULTS: Overall, 448 patients completed the 24-month follow-up, with a mean age of 51.6&#x2009;years at SARS-CoV-2 infection; 272 (60.7%) were women. A prior history of headaches was reported by 115 (25.7%). Patients with either pre-existing or de novo persistent headaches were younger, more often women, and exhibited hyposmia, hypogeusia, and headache during the acute phase of infection. De novo persistent headaches occurred in 54 of 333 (16.2%) headache-na&#xef;ve patients. Of these, 35 (64.8%) fulfilled migraine-like headache (MLH) criteria (mean age of 49.1&#x2009;years at 24-month follow-up), with a cumulative incidence of 42/1000/year.<br><br>CONCLUSIONS: De novo persistent headaches are common 2&#x2009;years after COVID-19, with MLH being the most frequent type. MLH incidence after COVID-19 is elevated and de novo "migraineurs-like" tend to be older compared to the general population. This is an important finding with potential implications for healthcare and quality of life, considering the high number of COVID-19 cases and the global burden of migraine.},
}
@article {pmid40386957,
year = {2025},
author = {},
title = {Corrigendum to "Clinical Phenotyping of Long COVID Patients Evaluated in a Specialized Neuro-COVID Clinic".},
journal = {Annals of clinical and translational neurology},
volume = {12},
number = {8},
pages = {1727},
doi = {10.1002/acn3.70069},
pmid = {40386957},
issn = {2328-9503},
}
@article {pmid40386506,
year = {2025},
author = {van Niekerk, I and Panieri, M and Müller, T and Mapahla, L and Dzanibe, S and Day, C and Stein, DJ and Peter, J},
title = {Acute serum protein biomarker profile and prevalence of persistent (&gt;6 months) neuropsychiatric symptoms in a cohort of SARS-CoV-2 PCR positive patients in Cape Town, South Africa.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {46},
number = {},
pages = {100990},
pmid = {40386506},
issn = {2666-3546},
abstract = {BACKGROUND: SARS-CoV-2 is a neurotrophic and pro-inflammatory virus, with several acute and more persistent neuropsychiatric sequelae reported. There are limited data from African cohorts and few acute illness biomarkers of persistent neuropsychiatric symptoms.<br><br>OBJECTIVES: To examine the association of neuropsychiatric outcomes with clinical illness severity, systemic inflammation, cardiovascular and renin-angiotensin-system (RAS) biomarkers. Second, to determine the prevalence of neuropsychiatric symptoms in a cohort of South African SARS-CoV-2 PCR positive patients at least six months following infection/hospitalization.<br><br>METHODOLOGY: SARS-CoV-2 PCR positive patients were recruited prospectively from Cape Town, South Africa, including hospitalized patients from ancestral, beta and delta-dominant COVID-19 waves (pre-vaccine rollout); and asymptomatic/mild SARS-CoV-2 positive patients. The 96-protein O-link inflammation and cardiovascular panels, RAS fingerprinting, and antibody responses were measured in serum samples collected at peak severity and recovery (>3 months post-infection). Telephonic interviews were conducted at least six months post infection/hospitalization. Validated measures employed were: WHO Self-Report Questionnaire (SRQ-20), Generalized Anxiety Disorder Scale (GAD-7), Chalder Fatigue Scale (CFS-11) and Telephonic Montreal Cognitive Assessment (T-MoCA).<br><br>RESULTS: Ninety-seven participants completed telephonic interviews. The median (IQR) age was 48 (37-59) years, and 54&#xa0;% were female. There were no significant associations between neuropsychiatric outcomes and illness severity, systemic inflammation, cardiovascular and/or renin-angiotensin-system (RAS) biomarkers from either peak illness or recovery samples. More than half of this SA COVID-19 cohort had one or more persistent neuropsychiatric symptoms >6 months post vaccine-na&#xef;ve infection. On the T-MoCA, 44&#xa0;% of participants showed evidence of cognitive and/or memory impairments.<br><br>CONCLUSION: The high prevalence of persistent neuropsychiatric symptoms in this African cohort supports ongoing attention to long COVID. Acute and early serum protein biomarkers were not associated with persistent neuropsychiatric outcomes post-COVD-19.},
}
@article {pmid40385629,
year = {2025},
author = {Bowie, C and Friston, K},
title = {Dynamic causal models in infectious disease epidemiology-an assessment of their predictive validity based on the COVID-19 epidemic in the UK 2020 to 2024.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1573783},
pmid = {40385629},
issn = {2296-2565},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *COVID-19/epidemiology ; Forecasting/methods ; United Kingdom/epidemiology ; Retrospective Studies ; *Epidemiological Models ; Prospective Studies ; SARS-CoV-2 ; Pandemics ; Reproducibility of Results ; Models, Statistical ; Bayes Theorem ; },
abstract = {This technical report addresses the predictive validity of long-term epidemiological forecasting based upon dynamic causal modeling. It uses complementary prospective and retrospective analyses. The prospective analysis completes a series of (annual) reports comparing predictions with subsequent outcomes (i.e., cases, deaths, hospital admissions and Long COVID) reported a year later. Predictive validity is then addressed retrospectively by examining predictions at various points during the pandemic, in relation to actual outcomes at three, six and 12 months after the predictions were evaluated. This analysis suggests that-with a sufficiently expressive dynamic causal model-three, six and 12 month projections can be remarkably accurate (to within 10% or less of observed outcomes) at certain phases of the epidemic: namely, the initial phase-before the emergence of highly transmissible variants-and toward the end of the pandemic, when slow fluctuations in transmissibility and virulence can be estimated more precisely. However, the predictive accuracy in the intervening periods are compromised, to the extent that some forecasts only remain within their Bayesian credible intervals for 3 months. We provide a quantitative analysis of predictive accuracy for future reference and discuss the implications for epidemiological modeling, and forecasting, of this sort.},
}
@article {pmid40385588,
year = {2025},
author = {Ranque, B and Cogan, E},
title = {Internal medicine at the crossroads of long COVID diagnosis and management.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1521472},
pmid = {40385588},
issn = {2296-858X},
abstract = {The lack of specificity in its definition is a major obstacle to both explanatory and therapeutic research in long COVID. It brings together, on the one hand, patients with severe COVID-19 who suffer the classic complications of prolonged hospitalization and decompensation of comorbidities and, on the other hand, patients with non-severe acute COVID-19 who report multiple symptoms that cannot be fully explained by a biomechanical model. Indeed, despite numerous studies, it remains unclear how persistent viral infection, immunological or coagulation disturbances may contribute mechanistically to long COVID. Nevertheless, internal medicine should be in good place to manage these patients. Indeed, the diversity of symptoms may evoke a broad spectrum of differential diagnoses that are familiar to internists. Their experience in the exploration of unexplained symptoms is also valuable. It can reduce the need for multiple consultations with specialists and unnecessary laboratory or imaging tests. However, long COVID diagnosis cannot be limited to the exclusion of all other conditions one by one. An open and non-dualistic approach is required to identify other mechanisms that may explain the symptoms. Based on their clinical experience, most French internists who responded to an opinion survey consider that long COVID corresponds most closely to a functional somatic disorder (FSD) and seek the help of specialists in mental health care to assist in the management of the patients in a multi-disciplinary approach. However, as with other FSDs, patients with long COVID are usually reluctant to be managed by mental health care specialists, given the very physical nature of their presentation. Unfortunately, most physicians are in turn reluctant to take care of them, due to poor knowledge about FSD, leading to management failure. Alternatively, a comprehensive multidisciplinary care orchestrated by an experienced internist is generally well-accepted. It includes providing rational cognitive explanations for the symptoms and support for behavioral changes tailored to the patient. While waiting for hypothetical randomized controlled trials assessing drugs with positive results, such a holistic approach has been successfully applied in many individuals with severe long COVID. However, its generalization would require a much broader training for FSD of all health care providers.},
}
@article {pmid40385408,
year = {2025},
author = {Yadaw, AS and Sid, E and Sidky, H and Zeng, C and Zhu, Q and Mathé, EA and , },
title = {Systematic identification of rare disease patients in electronic health records enables evaluation of clinical outcomes.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40385408},
support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; 75N90023D00001/CL/CLC NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U01 DA055358/DA/NIDA NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; 75N99023D00001/OF/ORFDO NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; 75N95021D00001/DA/NIDA NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; ZIC TR000410/ImNIH/Intramural NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; 75N94023D00001/HD/NICHD NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; 75N92023D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Identifying rare disease (RD) patients in electronic health records (EHR) is challenging, as more than 10,000 rare diseases are not typically captured by clinical coding systems. This limits the assessment of clinical outcomes for RD patients. This study introduces a semiautomated approach to map RDs to appropriate codes, that is applicable across various EHR systems. By improving RD patient identification, this method facilitates the analysis of clinical outcomes and disease severity in the RD population. We exemplify this by utilizing large EHR datasets such as those in the National COVID Cohort Collaborative (N3C) with over 21 million patients.<br><br>METHODS: We developed a semiautomated workflow to enumerate RD-specific SNOMED-CT and ICD-10 codes, starting with 12,003 GARD IDs mapped to ORPHANET. This process linked RDs to SNOMED-CT and ICD-10 codes, applying exclusion criteria based on group of disorders. We created an extensive list of SNOMED-CT codes with descendants from the OHDSI atlas and performed phenotype filtering, removing irrelevant codes. The final list included 12,081 SNOMED-CT codes and 357 ICD-10 codes for further analysis, enabling the identification and mapping of rare diseases in EHR.<br><br>RESULTS: Our semiautomated workflow identified 357 RD-specific ICD-10 codes and 12,081 SNOMED-CT codes representing 6,342 RDs which are categorized into 30 Orphanet linearization classes. We exemplify the utility of these codes by performing a preliminary univariate analysis of COVID-19 outcomes in a large cohort of 4,835,718 COVID-19 positive individuals in N3C, of which 404,735 (8.37%) were identified as having preexisting RD. The mortality and hospitalization risk ratios for rare RD classes ranged from 0.23 - 5.28 and 0.93 - 3.13, respectively (p-values <0.001).<br><br>CONCLUSIONS: Our systematic and automated workflow enables rapid identification of rare disease patients across diverse EHR systems. We demonstrate its utility by evaluating COVID-19 severity outcomes by rare disease classes in the N3C cohort. These findings support the need for targeted preventive healthcare interventions and highlight the potential for future research on long COVID, COVID-19 reinfection, and other outcomes in the rare disease population.},
}
@article {pmid40384184,
year = {2025},
author = {Rejinold N, S and Choi, G and Jin, GW and Choy, JH},
title = {Transforming Niclosamide through Nanotechnology: A Promising Approach for Long COVID Management.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {21},
number = {27},
pages = {e2410345},
pmid = {40384184},
issn = {1613-6829},
support = {//National Academy of Sciences, Republic of Korea/ ; },
mesh = {*Niclosamide/therapeutic use/chemistry ; Humans ; COVID-19/complications ; *Nanotechnology/methods ; SARS-CoV-2 ; Pandemics ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Betacoronavirus ; *Coronavirus Infections/drug therapy ; },
abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 770 million people worldwide. The long-term effects of COVID-19 and their management have become important issues. Accumulating evidence indicates that post-COVID-19 syndrome, also known as long COVID, is not limited to respiratory symptoms but affects a wide range of systems, including neurological, cardiovascular, gastrointestinal, musculoskeletal, and reproductive systems etc. The social and economic losses associated with these effects are estimated to reach 3·7 trillion dollars in the United States alone. However, no treatment for long COVID has been developed. Herein, the literature on long COVID is comprehensively reviewed to examine the underlying causes. Additionally, evidence supporting the efficacy of nanoengineered niclosamide is presented, given its ability to counteract the underlying causes. Niclosamide is already Food and Drug Administration (FDA)-approved, and the nanoengineered one is a viable candidate for clinical trials for long COVID.},
}
@article {pmid40384037,
year = {2026},
author = {González Rosas, Z and Martínez-Jiménez, HS and Arroyo-Landín, M and Fragoso, G and Chávez-Canales, M and Hernández, M and Rosetti, MF and López-Alvarenga, JC and Sciutto, E and Cárdenas, G},
title = {Long-Term Neuropsychiatric Sequelae of COVID-19 in an Open Population: A Prospective Pilot Study.},
journal = {The Journal of neuropsychiatry and clinical neurosciences},
volume = {38},
number = {1},
pages = {68-75},
doi = {10.1176/appi.neuropsych.20240040},
pmid = {40384037},
issn = {1545-7222},
mesh = {Humans ; *COVID-19/complications/psychology/blood ; Male ; Pilot Projects ; Female ; Prospective Studies ; Middle Aged ; Adult ; Kynurenine/blood ; Quinolinic Acid/blood ; Longitudinal Studies ; Tryptophan/blood ; Lipopolysaccharides/blood ; Aged ; Neuropsychological Tests ; *Mental Disorders/etiology ; *Cognitive Dysfunction/etiology ; },
abstract = {OBJECTIVE: COVID-19 has been associated with a wide range of systemic and neurological complications, known as long COVID or postacute sequelae of COVID-19 (PASC). Such sequelae can be observed among all infected individuals, even among those with a mild disease course. Dysbiosis, a common condition associated with low-grade inflammation, has been proposed as a potential mechanism of PASC by altering levels of circulating lipopolysaccharide (LPS) and the tryptophan pathway metabolites kynurenine and quinolinic acid, known to affect neurocognitive function. The authors evaluated the evolution of neurological, neurocognitive, and neuropsychiatric COVID-19 sequelae and their relationship with circulating LPS and kynurenine and quinolinic acid levels.<br><br>METHODS: A prospective, longitudinal, and analytical study was conducted. Neurological, neurocognitive, and neuropsychiatric assessments of participants who had recovered from COVID-19 and did not require hospitalization during the acute stages of the infection were performed. Peripheral levels of LPS and tryptophan metabolites were measured 1, 3, 6, and 12 months after infection.<br><br>RESULTS: Of 95 participants recruited, 67 COVID-19-convalescent individuals and 20 COVID-19-free individuals were included. Significantly higher occurrences of asthenia, olfaction and taste alterations, headache, memory dysfunction, and systemic symptoms such as dyspnea, cough, and periodontal diseases were found among participants in the COVID-19-convalescent group compared with participants in the comparison group. A significant decrease in kynurenine levels, which correlated with cognitive impairment, was observed among PASC convalescents.<br><br>CONCLUSIONS: Significant neurocognitive and neuropsychiatric impairments were observed among COVID-19-convalescent individuals, along with decreased kynurenine levels, which recovered during a 12-month follow-up period.},
}
@article {pmid40383636,
year = {2025},
author = {Kogure, Y and Ando, W and Sakamaki, K and Sugawara, M},
title = {Treatment of Long Coronavirus Disease in Japan: A Nationwide Study of Symptom-Associated Drug Prescriptions.},
journal = {Biological &amp; pharmaceutical bulletin},
volume = {48},
number = {5},
pages = {641-649},
doi = {10.1248/bpb.b24-00762},
pmid = {40383636},
issn = {1347-5215},
mesh = {Humans ; Japan/epidemiology ; Middle Aged ; Male ; Female ; Adult ; *COVID-19/complications/epidemiology ; Aged ; *COVID-19 Drug Treatment ; *Drug Prescriptions/statistics &amp; numerical data ; Medicine, Kampo ; Aged, 80 and over ; Drugs, Chinese Herbal/therapeutic use ; Young Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Adolescent ; Databases, Factual ; },
abstract = {Long coronavirus disease (COVID) is characterized by symptoms persisting or reappearing at least 2 months post-recovery from acute coronavirus disease 2019 (COVID-19). Although Long COVID symptoms have been widely studied, data on drug prescriptions for patients with Long COVID in Japan remain limited. Therefore, this study aimed to analyze drug utilization patterns for Long COVID treatment using a nationwide database in Japan, with the goal of providing basic data to support the establishment of standard treatments in the future. The Medical Data Vision COVID-19 dataset was used to identify patients diagnosed with Long COVID between January 15, 2020 and December 31, 2022. Symptoms and prescribed medications were extracted, and descriptive statistics were used to analyze the relationship between symptoms and drug prescriptions. Among 652016 patients with COVID-19, 3769 (0.6%) developed Long COVID. Common symptoms included fatigue, bronchial asthma-like symptoms, and insomnia. Acetaminophen was the most prescribed drug in the first month of diagnosis. Other frequently prescribed drugs included dextromethorphan, l-carbocisteine, and polaprezinc. From 3 months post-diagnosis, prescriptions for Hochu-ekki-to (a traditional Japanese herbal medicine; Kampo medicine) and polaprezinc increased, especially among patients aged 30-50 years. Long COVID in Japan is characterized by a wide range of symptoms, leading to symptom-based drug prescriptions, particularly fatigue, respiratory issues, and taste disturbances. These findings offer insights into the pharmacological management of Long COVID in Japan, highlighting the need for further research on optimal treatments in the future.},
}
@article {pmid40382191,
year = {2025},
author = {Martins, BAA and Garcia, ALH and Borges, MS and Nobles, DDR and Hansen, AW and Spilki, FR and Schuler-Faccini, L and Rampelotto, PH and da Silva, J},
title = {Acute and chronic post-COVID-19 conditions: A study of genetic integrity and clinical markers.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {904},
number = {},
pages = {503870},
doi = {10.1016/j.mrgentox.2025.503870},
pmid = {40382191},
issn = {1879-3592},
mesh = {Humans ; Female ; *COVID-19/genetics/complications/blood/virology ; Male ; Middle Aged ; Adult ; *Genomic Instability ; SARS-CoV-2 ; Oxidative Stress ; DNA Damage ; Biomarkers/blood ; Chronic Disease ; Inflammation/genetics ; Brazil ; Post-Acute COVID-19 Syndrome ; Aged ; },
abstract = {The long-term effects of COVID-19 infection on genomic integrity, along with hematological, biochemical, and inflammatory, remain poorly understood. Viral infections, including SARS-CoV-2, are known to induce genomic instability, potentially contributing to the persistence of post-COVID-19 symptoms. This study aimed to assess genomic instability in individuals with acute and chronic post-COVID-19 conditions, alongside hematological profiles, metabolic parameters, and inflammatory markers, compared to a SARS-CoV-2-negative control group. Participants (n = 231) from southern Brazil were stratified into acute post-COVID (n = 78), chronic post-COVID (n = 79), and control groups (n = 74). DNA damage was assessed using alkaline and enzyme-modified comet assays. Oxidative lesions were detected across all groups, but no significant differences were observed among them. Correlations with biochemical markers suggest inflammation and oxidative stress as central mechanisms in post-COVID-19 pathophysiology. Hematological and biochemical analyses revealed persistent inflammation, lipid metabolism disruptions, and gender-specific alterations, such as higher levels of inflammatory markers (C-reactive protein and ferritin) and lipid abnormalities in men, whereas women exhibited distinct hematological patterns. Age-related influences on metabolic and inflammatory markers further illustrate the systemic complexity of post-COVID-19 effects. The chronic group exhibited ongoing but attenuated markers of inflammation and oxidative stress compared to the acute group. These findings suggest that genetic instability alone may not fully explain the observed clinical manifestations, emphasizing the role of persistent inflammation and metabolic dysregulation. This study provides a comprehensive view of the interplay between genomic instability, inflammation, oxidative damage, and systemic alterations in post-COVID-19 condition. It underscores the importance of a multifaceted approach to understanding disease mechanisms and the need for longitudinal studies to explore the dynamic nature of these alterations and their long-term health implications.},
}
@article {pmid40380585,
year = {2025},
author = {Prgomet, M and Kamalakkannan, A and Thomas, J and Pearce, C and McLeod, A and Gardner, K and Georgiou, A},
title = {Identifying Long COVID Patients Using General Practice Data: Challenges, Classification and Long COVID Patterns.},
journal = {Studies in health technology and informatics},
volume = {327},
number = {},
pages = {838-842},
doi = {10.3233/SHTI250477},
pmid = {40380585},
issn = {1879-8365},
mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; *Electronic Health Records/statistics &amp; numerical data ; Female ; Adult ; *General Practice/statistics &amp; numerical data ; Male ; Middle Aged ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {General practice data, extracted from electronic medical records, holds immense potential to generate a wealth of public health knowledge. But it is not without challenges. Our aim in this study was to identify long COVID patients within a large general practice dataset through data classification. We discuss the classification and its validation, and present initial data patterns for the identified long COVID cohort. We found significant variation in how general practitioners document and describe long COVID presentations. Less than half of the identified long COVID patients had a documented acute COVID infection. The highest proportion of long COVID patients were female and those 40-49 years of age. Overall, this study highlights key lessons for researchers utilizing general practice data, particularly in the context of long COVID, and underscores the vital importance of collaboration between researchers, general practitioners, and data custodians to ensure the robustness of data underpinning knowledge translation.},
}
@article {pmid40379782,
year = {2025},
author = {Chu, AMY and Tsang, JTY and Chan, SSC and Chan, LSH and So, MKP},
title = {Utilizing Google Trends data to enhance forecasts and monitor long COVID prevalence.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {179},
pmid = {40379782},
issn = {2730-664X},
support = {SBMDF21BM07//Hong Kong University of Science and Technology (HKUST)/ ; },
abstract = {BACKGROUND: Long COVID, the persistent illness following COVID-19 infection, has emerged as a major public health concern since the outbreak of the pandemic. Effective disease surveillance is crucial for policymaking and resource allocation.<br><br>METHODS: We investigated the potential of utilizing Google Trends data to enhance long COVID symptoms surveillance. Though Google Trends provides freely available search popularity data, limitations in data normalization and retrieval restrictions have hindered its predictive capabilities. In our study, we carefully selected 33 search terms and 20 related topics from the long COVID symptoms list provided by the Centers for Disease Control and Prevention and the database "scite", and calculated their merged search volumes from Google Trends data using our developed statistical method for analysis.<br><br>RESULTS: We identify four related topics (ageusia, anosmia, chest pain, and headaches) that consistently exhibit increased search popularity before that of "long COVID." Additionally, nine related topics (aching muscle pain, anxiety, chest pain, clouding of consciousness, dizziness, fatigue, myalgia, shortness of breath, and hypochondriasis) show increased search popularity following that of "long COVID." We demonstrate that the merged search volume (MSV), derived from the relative search volume data downloaded from Google, can be used to forecast the prevalence of long COVID in a prediction study, supporting the use of the methodology in risk management regarding the prevalence of long COVID.<br><br>CONCLUSIONS: By utilizing a comprehensive list of search terms and sophisticated statistical analytics, our study contributes to exploring the potential of Google Trends data for forecasting and monitoring long COVID prevalence. These findings and methodologies can be used as prior knowledge to inform future infodemiological and epidemiological investigations.},
}
@article {pmid40379198,
year = {2025},
author = {Maqsood, K and Ahmad, S and Saeed, A and Roohi, N},
title = {Plasma protein biomarkers for long COVID-19: Predictors of symptom severity and mortality risk.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {575},
number = {},
pages = {120350},
doi = {10.1016/j.cca.2025.120350},
pmid = {40379198},
issn = {1873-3492},
mesh = {Humans ; *COVID-19/mortality/blood/diagnosis ; Biomarkers/blood ; Male ; Female ; Middle Aged ; *Blood Proteins/analysis ; Severity of Illness Index ; Aged ; Adult ; Prognosis ; SARS-CoV-2 ; Haptoglobins/analysis ; Fibrinogen/analysis ; },
abstract = {INTRODUCTION: Long COVID-19 is marked by persistent symptoms beyond the acute phase, necessitating a deeper understanding of mortality risk factors for effective management. Plasma proteins hold promise as prognostic markers, offering insights into disease progression and aiding in mortality risk assessment.<br><br>METHOD: A total of 240 patients and 89 healthy controls were enrolled for this study. Two months post-COVID follow-up, patients were categorized as survivors (n&#xa0;=&#xa0;212) and non-survivors (n&#xa0;=&#xa0;28). Plasma samples underwent 2-dimensional Gel Electrophoresis (2DE) for protein separation, followed by LC-MS/MS for protein identification, and validation was performed using ELISA. Proteomic data analysis was conducted using Mascot version 2.3.02 and Samespots software 4.5.1. Statistical analyses were carried out using GraphPad Prism and IBM SPSS.<br><br>RESULTS: LC-MS/MS identified fibrinogen (Spot 14; 52.15&#xa0;kDa/5.32 pI; protein score 2293) and haptoglobin (Spot 08; 45.86&#xa0;kDa/6.56 pI; protein score 453) as prospective predictive biomarkers. ELISA results confirmed increased plasma levels of fibrinogen and haptoglobin in severe cases (P&#xa0;<&#xa0;0.001 for both) and non-survivors (P&#xa0;<&#xa0;0.01 and P&#xa0;<&#xa0;0.0086, respectively). ROC analysis showed haptoglobin had moderate predictive power for mortality (AUC&#xa0;=&#xa0;0.68; P&#xa0;=&#xa0;0.0025), surpassing fibrinogen (AUC&#xa0;=&#xa0;0.62; P&#xa0;=&#xa0;0.0374).<br><br>CONCLUSION: Plasma fibrinogen and haptoglobin are promising biomarkers for assessing disease severity and mortality risk in long COVID. These findings highlight their potential for prognostic applications, warranting further research into their mechanistic roles in COVID-19 and broader clinical implications.},
}
@article {pmid40376340,
year = {2025},
author = {Batra, VA and Unarkat, KB and Kaur, M and Ahluwalia, H and Manna, S},
title = {Post-COVID Condition Does Not Alter Cognitive Functions in Young Adults: A Cross-Sectional Study in North India.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82208},
pmid = {40376340},
issn = {2168-8184},
abstract = {Background Long COVID, or post-COVID condition, includes multi-system chronic sequelae that can last weeks, months, or even years in some individuals after recovery from COVID-19 infection. Prominent among these long-term sequelae are cognitive deficits that may prove to be problematic, especially for the working young adult population. The present study aimed to determine whether cognitive deficits are observed long after recovery from mild COVID-19 infection. Methods In this cross-sectional observational study, 29 young adult undergraduate medical students with a history of mild COVID-19 infection at least two years prior were included as cases, while 29 age- and sex-matched undergraduate medical students with no history of COVID-19 were recruited as controls. Sociodemographic data were collected, and the participants were then administered a series of cognitive tests using the National Institutes of Health (NIH) Toolbox V3 software (Toolbox Assessments Inc., Chicago, USA; https://nihtoolbox.org/) to evaluate the cognitive functions, including executive function, cognitive flexibility, attention, working and episodic memory, and processing speed. Results The mean age of the cases and controls was 19.37 ± 0.92 and 19.65 ± 0.99 years, respectively. However,there was no statistically significant difference in cognitive function performance across any of the tested domains between cases and controls. Conclusion The results of our study indicate that, compared to healthy controls, cognitive functions were not impaired in young adults who previously had symptomatic mild COVID-19 infection.},
}
@article {pmid40375203,
year = {2025},
author = {Vallée, A and Arutkin, M and Ceccaldi, PF and Feki, A and Ayoubi, JM},
title = {Long COVID and endometriosis: a systematic review and meta-analysis.},
journal = {BMC women's health},
volume = {25},
number = {1},
pages = {229},
pmid = {40375203},
issn = {1472-6874},
mesh = {Humans ; *Endometriosis/epidemiology/complications ; Female ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; },
abstract = {Long COVID conditions entail the persistence of COVID-19-related symptoms for at least eight weeks following SARS-CoV-2 infection. The prevalence of long COVID is estimated to range from 10 to 30% among individuals infected with SARS-CoV-2. Despite its growing impact on healthcare systems, long COVID remains poorly understood. In parallel, endometriosis, a chronic inflammatory condition affecting around 10% of reproductive-age women, is marked by symptoms such as pelvic pain and infertility. The aim of this study was to assess the association between endometriosis and long COVID. We performed a systematic review of long COVID among endometriosis patients in Pubmed/Medline, Cochran Library and Science Direct databases from inception to August 2023. We independently selected studies, extracted data, assessed risk of bias, and compared endometriosis versus non endometriosis patients for long. Pooled analyses were based on random-effect models, and the I[2] statistic was used to quantify heterogeneity across studies. A total of 2 cross-sectional studies (N = 216,095 participants) were included. The pooled analysis comparing endometriosis to non-endometriosis patients significantly showed association for long COVID (pooled RR = 1.41 [1.31-1.52], I[2] = 29%, p < 0.001). Women, who are disproportionately affected by long COVID, particularly those with endometriosis, may face compounded health challenges. While our findings suggest a possible association between endometriosis and long COVID, the evidence is currently limited to two observational studies. Further research involving diverse populations and robust study designs is needed to confirm this relationship and clarify underlying mechanisms.},
}
@article {pmid40375188,
year = {2025},
author = {Dai, Z and Liu, X and Jing, S and Wang, H and Huang, Y and Fu, J and Wu, Y and Zhang, L and Han, B and Su, X},
title = {Development and internal validation of a depressive symptoms prediction model among the patients with cardiovascular disease who have recovered from SARS-CoV-2 infection in Wuhan, China: a cross-sectional study.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {492},
pmid = {40375188},
issn = {1471-244X},
support = {2020-I2M-2-015//The Innovative Engineering Program sponsored by the Chinese Academy of Medical Sciences/ ; CAMS 2021-I2M-1-004//CAMS Innovation Fund for Medical Sciences/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology ; Cross-Sectional Studies ; Male ; Female ; China/epidemiology ; Middle Aged ; *Cardiovascular Diseases/psychology/epidemiology ; Aged ; *Depression/epidemiology/diagnosis/etiology ; Prevalence ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Middle-aged and elderly patients with cardiovascular disease (CVD) who have recovered from SARS-CoV-2 infection may experience depressive symptoms due to the physical and psychological impact of the pandemic.<br><br>OBJECTIVE: To investigate the prevalence and predictors of depressive symptoms among the middle-aged and elderly with CVD who have recovered from SARS-CoV-2 infection in Wuhan, China, and to develop a prediction model for depressive symptoms.<br><br>METHODS: A cross-sectional study was conducted among 462 former SARS-CoV-2 middle-aged and elderly patients with CVD in Jianghan District, Wuhan, China from June 10 to July 25, 2021. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Potential predictors of depressive symptoms were selected by the least absolute shrinkage and selection operator (LASSO) regression. A prediction model was developed by random forest (RF) and logistic regression models and compared by the area under the receiver operating characteristic curve (AUROC). The discrimination, calibration, and practical utility of the prediction model were evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Bootstrap sampling was used for internal validation.<br><br>RESULTS: The prevalence of depressive symptoms among the participants was 35.93%. The prediction model included age, stethalgia after recovery, insomnia after recovery, post-traumatic stress disorder (PTSD), anxiety, fatigue, and perceived social support as predictors. The AUROC of the logistic regression model was 0.909 (95%CI: 0.879&#x2009;~&#x2009;0.939), indicating good discrimination. The calibration curve showed good calibration. The DCA showed that the prediction model had a net benefit for a wide range of risk thresholds. The internal validation confirmed the stability of the prediction model.<br><br>CONCLUSION: Depressive symptoms are common among middle-aged and elderly CVD patients who have recovered from SARS-CoV-2 infection in Wuhan, China. A prediction model with satisfactory performance was developed to estimate the risk of depressive symptoms among this population. Interventions targeting long COVID symptoms and social support should be considered to prevent depressive symptoms in CVD patients.},
}
@article {pmid40374074,
year = {2025},
author = {Canziani, LM and Monforte, AD and Giannella, M and Rodríguez-Baño, J and Tacconelli, E},
title = {Bridging the evidence gap: expert consensus on management of SARS-CoV-2 acute infection and post-COVID-19 condition in immunocompromised patients.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {31},
number = {8S},
pages = {S1-S2},
doi = {10.1016/j.cmi.2025.05.008},
pmid = {40374074},
issn = {1469-0691},
}
@article {pmid40372987,
year = {2025},
author = {Lawrence, MR and Arnetz, JE and Counts, SE and Ahmed, A and Arnetz, BB},
title = {Self-reported health, neuropsychological tests and biomarkers in fully recovered COVID-19 patients vs patients with post-COVID cognitive symptoms: A pilot study.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0315486},
pmid = {40372987},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/psychology/complications ; Middle Aged ; Pilot Projects ; Male ; Female ; Biomarkers/blood ; Adult ; Self Report ; Neuropsychological Tests ; Aged ; Case-Control Studies ; Quality of Life ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; },
abstract = {Substantial numbers of individuals who contract COVID-19 experience long-lasting cognitive symptoms such as brain fog. Yet research to date has not compared these patients with healthy controls with a history of laboratory-confirmed COVID-19 infection, making it difficult to understand why certain COVID patients develop post-COVID cognitive symptoms while others do not. The objective of this pilot study was to compare two groups of laboratory-confirmed post-COVID patients, with and without cognitive symptoms, on measures of cognitive and psychological functioning, self-reported perceptions of functional status and quality of life, and biomarkers of stress, inflammation, and neuroplasticity. Using a case-control design, 17 participants were recruited from a healthcare system in western Michigan, USA in 2022-2024. All participants were aged 25-65 and had a positive polymerase chain reaction (PCR) test confirming previous COVID-19 infection. Ten participants reported cognitive symptoms (long COVID group) while seven were fully recovered with no residual symptoms (controls). All participants underwent an interview on their self-rated health and quality of life, a battery of neurocognitive tests, and blood draw for biomarker analysis. No group differences were detected for neuropsychological test measures except for letter fluency where the long COVID group scored significantly lower (p < .05). The long COVID group had significantly lower ratings than controls on quality of life, physical health, emotional functioning, and psychological well-being. Serum levels of nerve growth factor (NGF), a biomarker of brain plasticity, were significantly lower in the long COVID group, which was significantly more likely than controls to have serum levels of inflammatory marker (interleukin (IL)-10) values greater than or equal to the median (p = 0.015). Biomarker analyses suggest possible prolonged inflammatory processes in long COVID patients compared to fully recovered patients. Results of decreased neuroplastic functioning give credence to patients' reports of post-COVID changes in brain function.},
}
@article {pmid40371440,
year = {2025},
author = {Abul, Y and Harris, DA and Chachlani, P and Hayes, KN and Zullo, AR and Mor, V and Gravenstein, S},
title = {Incidence of Long COVID Diagnoses in 3.6 Million U.S. Medicare Beneficiaries With COVID-19.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {80},
number = {7},
pages = {},
pmid = {40371440},
issn = {1758-535X},
support = {U54 AG063546/AG/NIA NIH HHS/United States ; U54AG063546/NH/NIH HHS/United States ; },
mesh = {Humans ; United States/epidemiology ; *COVID-19/epidemiology/diagnosis/prevention &amp; control ; Aged ; Male ; Incidence ; Female ; Aged, 80 and over ; *Medicare/statistics &amp; numerical data ; SARS-CoV-2 ; *COVID-19 Vaccines/administration &amp; dosage ; Risk Factors ; Cohort Studies ; Vaccination/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Long COVID incidence and risk factors in older adults need to be better characterized to identify risk mitigation strategies. Our aim was to quantify the incidence of Long COVID in a population-based sample of older adults and to describe the association between COVID-19 vaccination and Long COVID risk.<br><br>METHODS: This cohort study included Medicare fee-for-service beneficiaries&#x2005;&#x2265;&#x2005;66 years diagnosed with COVID-19 between October 1, 2021, and March 31, 2023 (index date). Long COVID diagnoses were identified from Medicare Part A-B claims based on ICD-10-CM code U09.9. We measured the number of COVID-19 vaccine doses administered prior to the index date using Medicare Part B claims and pharmacy records. Kaplan-Meier estimators, Cox proportional hazards, and Fine-Grey regression models were used to estimate the 1-year cumulative incidence and relative rate of Long COVID.<br><br>RESULTS: We identified 3&#x2009;588&#x2009;671 Medicare beneficiaries diagnosed with COVID-19. Overall, 3.89% of beneficiaries were diagnosed with Long COVID over 1 year. A gradient in the 1-year cumulative incidence of Long COVID was observed according to the number of prior COVID-19 vaccine doses. Beneficiaries with 4 or more COVID-19 vaccine doses had a 39% lower adjusted rate of Long COVID relative to beneficiaries without a prior dose (adjusted hazard ratio&#x2005;=&#x2005;0.61, 95% CI&#x2005;=&#x2005;0.60-0.62).<br><br>CONCLUSIONS: Long COVID diagnoses in Medicare claims were common in a large sample of older adults with COVID-19, and we observed a gradient in Long COVID risk across the number of prior COVID-19 vaccine doses. Promoting continued vaccination may be an effective strategy to mitigate the burden of Long COVID in older adults.},
}
@article {pmid40368776,
year = {2025},
author = {Aikawa, T and Ogino, J and Funayama, N and Oyama-Manabe, N and Minamino, T},
title = {Vasospastic Angina as a Cause of Post-Acute Sequelae of COVID-19.},
journal = {International heart journal},
volume = {66},
number = {3},
pages = {504-510},
doi = {10.1536/ihj.24-795},
pmid = {40368776},
issn = {1349-3299},
mesh = {Humans ; *COVID-19/complications ; Male ; Retrospective Studies ; Female ; *Coronary Vasospasm/diagnosis/etiology/complications ; Middle Aged ; Aged ; SARS-CoV-2 ; Japan/epidemiology ; *Angina Pectoris/etiology/diagnosis ; *Chest Pain/etiology ; Post-Acute COVID-19 Syndrome ; Acetylcholine ; },
abstract = {Diagnosing the cause of post-acute sequelae of COVID-19 (PASC, also known as long COVID)-related chest pain is often challenging in patients with a low pre-test probability of coronary artery disease. In a retrospective review of 273 consecutive patients who presented to the cardiovascular outpatient unit for cardiovascular PASC at the Hokkaido Cardiovascular Hospital, Japan, 8 patients were suspected to have vasospastic angina (VSA) and underwent acetylcholine provocation testing, 5 of whom (1.8%, 5/273) were newly diagnosed with VSA. Although the causal relationship between VSA and PASC should be studied further, the present study suggests that VSA can be a potential cause of chest pain in patients with PASC.},
}
@article {pmid40367788,
year = {2025},
author = {Numata, S and Nakatani, Y and Takamatsu, K and Yokoyama, A},
title = {Post-COVID-19 condition in patients receiving invasive positive pressure ventilation or high flow nasal cannula therapy.},
journal = {Respiratory investigation},
volume = {63},
number = {4},
pages = {617-622},
doi = {10.1016/j.resinv.2025.05.004},
pmid = {40367788},
issn = {2212-5353},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Cannula ; *COVID-19/therapy/complications/physiopathology ; Japan ; Noninvasive Ventilation ; *Oxygen Inhalation Therapy/methods ; *Positive-Pressure Respiration/methods/adverse effects ; Propensity Score ; Respiratory Function Tests ; Severity of Illness Index ; Tomography, X-Ray Computed ; *Post-Acute COVID-19 Syndrome/epidemiology/etiology ; },
abstract = {BACKGROUND: Invasive positive pressure ventilation (IPPV) and high-flow nasal cannula (HFNC) are often employed for severe COVID-19 patients. Such advanced respiratory support might influence the post-COVID-19 condition (PCC). Here, we investigated the potential association between advanced respiratory support and PCC.<br><br>METHODS: This study is ancillary to the separately reported multicenter observational study that included moderate to severe COVID-19 patients who required hospitalization between September 2020 and September 2021 in Japan. PCC symptoms, chest CT images, and lung function tests were evaluated 3 months after discharge. Frequency of PCC was compared between patients with and without advanced respiratory support using propensity score matching including severity on admission.<br><br>RESULTS: Among 714 participants, 100 received advanced respiratory support (IPPV: 56, HFNC: 44). Patients who received advanced respiratory support significantly more frequently had PCC symptoms, CT abnormalities, and lung dysfunction. However, comparison of propensity score-matched controls indicated no significant differences in the frequency of symptoms, although CT and lung function abnormalities remained significantly higher. Furthermore, these differences were only observed in elderly patients. There were no differences in the frequency of PCC between patients with IPPV versus HFNC therapy.<br><br>CONCLUSIONS: Patients treated with IPPV or HFNC showed more PCC symptoms that were largely related to the initial disease severity. CT and pulmonary function abnormalities were also more frequent in such patients, especially the elderly, although this showed no correlation with disease severity. These findings underscore the correlation between age and PCC in COVID-19 patients who received advanced respiratory support. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) under the identifier UMIN000041168.},
}
@article {pmid40366711,
year = {2025},
author = {Vu, PD and Abdi, S},
title = {Post-acute sequelae SARS-CoV-2 infection and neuropathic pain: a narrative review of the literature and future directions.},
journal = {Pain management},
volume = {15},
number = {6},
pages = {333-343},
pmid = {40366711},
issn = {1758-1877},
mesh = {Humans ; *Neuralgia/etiology/therapy/epidemiology/physiopathology ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {PURPOSE OF REVIEW: Neuropathic pain is a recognized and debilitating symptom of SARS-CoV-2 infection across acute, post-acute, and long-COVID phases. Initially emerging as acute or subacute symptoms, these neuropathic manifestations can evolve into chronic conditions, with approximately 10% of all SARS-CoV-2 cases (estimated 65 million individuals globally) developing post-acute SARS-CoV-2 (PASC) neuropathic sequalae. Given the limited literature specifically addressing neuropathic pain related to PASC, a deeper understanding is needed to improve management and reduce patient burden.<br><br>RECENT FINDINGS: PASC symptoms are associated with disease severity, elevated body mass indexes, preexisting psychological conditions, and addiction history. Sex differences appear to influence prevalence, and the multisystem nature of PASC complicates symptom presentation, with mood disorders, fatigue, and cognitive dysfunction contributing to altered pain perception. Proposed mechanisms include immune dysregulation, persistent viral protein effects, and neuroanatomical changes. Management typically involves a multimodal approach.<br><br>SUMMARY: This review examines SARS-CoV-2 neuropathic pain across the illness trajectory, examining its pathophysiology, prevalence, and treatment. It highlights the potential for subacute neuropathic symptoms to become chronic and calls for future research to refine long-term management strategies and assess broader healthcare implications.},
}
@article {pmid40365982,
year = {2025},
author = {Ortega-Martin, E and Alvarez-Galvez, J},
title = {Living With Long COVID: Everyday Experiences, Health Information Barriers and Patients' Quality of Life.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70290},
pmid = {40365982},
issn = {1369-7625},
support = {//This research was conducted by E.O.-M. under a predoctoral research contract at the University of C&#xe1;diz (UCA/REC44VPCT/2021). The present study has been supported by the project DCODES (PID2020-118589RB-I00), granted by the Spanish Ministry of Science and Innovation and financed by MCIN/AEI/10.13039/501100011033./ ; },
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/psychology/complications ; Female ; Male ; Middle Aged ; Spain ; Aged ; Qualitative Research ; Interviews as Topic ; Adult ; SARS-CoV-2 ; Chronic Disease ; Social Stigma ; },
abstract = {BACKGROUND: Long COVID has considerably impacted patients' daily lives, yet qualitative insights in Spain are still scarce. This study seeks to (1) explore patients' experiences and the barriers they face, (2) analyse challenges in accessing accurate information and (3) evaluate the effects on quality of life by examining its dimensions in detail.<br><br>METHODS: Semi-structured interviews were conducted with 23 participants in Spain with Long COVID. Thematic analysis was performed, investigating needs, obstacles in daily life, challenges in obtaining and understanding health knowledge and its effects on the quality of life.<br><br>RESULTS: The most frequent symptoms were chronic pain and postexercise fatigue. All individuals encountered restrictions in their daily lives, which often had financial consequences. A lack of recognition coupled with legal insecurity due to the absence of a formal diagnosis further compromised their economic stability. Stigmatisation and poor social understanding led to feelings of loneliness and distress, adding to the overall impact of the disease. Health fragmentation, lack of follow-up and absence of coordinated multidisciplinary treatment limited specialised treatment and health information. Therefore, many patients sought information and support from online communities. However, misinformation and information overload or contradictory information generated confusion, affecting decision-making about the management of their disease, affecting disease management and quality of life.<br><br>CONCLUSION: The impact of Long COVID transcends physical health, pointing to economic pressure, legal uncertainty and fragmentation of care. We reveal how misinformation and a lack of guidance intensify inequities in access to reliable information. These findings underscore the need for integrated models of care, policy recognition and targeted strategies to reduce socio-economic inequalities.<br><br>This study expands knowledge about the experiences of people with Long COVID in Spain. Their journeys in the healthcare system and the challenges they face are key to the analysis and findings. Patient associations supported recruitment to ensure a broad range of viewpoints.},
}
@article {pmid40365527,
year = {2025},
author = {Sun, H and Dang, R and Haack, M and Hauser, K and Scott-Sutherland, J and Westover, MB and Parthasarathy, S and Redline, S and Thomas, RJ and Mullington, JM},
title = {Facility-measured nocturnal hypoxemia and sleep among adults with long COVID versus age- and sex-matched healthy adults: a preliminary observational study.},
journal = {Sleep advances : a journal of the Sleep Research Society},
volume = {6},
number = {2},
pages = {zpaf017},
pmid = {40365527},
issn = {2632-5012},
abstract = {STUDY OBJECTIVES: Persistent post-acute sequelae of SARS-CoV-2 infection, i.e. long COVID, impacts multiple organ systems. While lower blood oxygen is expected when SARS-CoV-2 infects the lungs, hypoxia without pulmonary symptoms may continue after the acute phase. Ventilation and blood oxygen are more vulnerable during sleep, but nocturnal hypoxemia hasn't been studied in people with long COVID in a facility setting using gold-standard polysomnography (PSG).<br><br>METHODS: We conducted an observational study with 50 participants (25 long COVID, 25 age-sex-matched healthy controls) using in-laboratory overnight PSG. We calculated the average SpO2, average SpO2 after removing desaturations, the respiratory rate in different sleep periods, and the hypoxic costs using all desaturations.<br><br>RESULTS: We found that average SpO2 was lower in participants with long COVID: 1.0% lower after sleep onset (p&#x2005;=&#x2005;.004) and 0.7% lower during REM (p&#x2005;=&#x2005;.002); average SpO2 after removing desaturations was also lower in participants with long COVID: 1.3% lower after sleep onset (p&#x2005;=&#x2005;.002), 0.9% lower during REM (p&#x2005;=&#x2005;.0004), and 1.4% lower during NREM (p&#x2005;=&#x2005;.003); and respiratory rate was 1.4/minute higher in participants with long COVID during REM (p&#x2005;=&#x2005;.005). There were no significant differences in SpO2 and respiratory rate before sleep onset, the within-participant change from before to after sleep onset, or hypoxic costs.<br><br>CONCLUSIONS: The results suggest that long COVID had a persistent lower nocturnal blood oxygen saturation, and support the need for a large-scale study of nocturnal hypoxemia in people with long COVID compared to the general population.},
}
@article {pmid40364149,
year = {2025},
author = {Brewer, KD and Santo, NV and Samanta, A and Nag, R and Trotsyuk, AA and Rajadas, J},
title = {Advances in Therapeutics for Chronic Lung Diseases: From Standard Therapies to Emerging Breakthroughs.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364149},
issn = {2077-0383},
abstract = {Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies.},
}
@article {pmid40364089,
year = {2025},
author = {Moustakli, E and Stavros, S and Michaelidis, TM and Potiris, A and Christodoulaki, C and Zachariou, A and Drakakis, P and Zikopoulos, K and Domali, E and Zikopoulos, A},
title = {Long-Term Effects of COVID-19 on Women's Reproductive Health and Its Association with Autoimmune Diseases, Including Multiple Sclerosis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364089},
issn = {2077-0383},
abstract = {Concern over COVID-19's long-term influence on women's reproductive health is growing, with emerging research suggesting potential links to ovarian dysfunction, menstrual irregularities, fertility challenges, and adverse pregnancy outcomes. Post-viral immune dysregulation is linked to both the development and exacerbation of autoimmune diseases, including multiple sclerosis (MS). Long COVID has been associated with immunological dysfunction, hormonal imbalances, and chronic inflammation, all of which may worsen autoimmune disorders and reproductive health issues. Long COVID is characterized by symptoms persisting for weeks or months beyond the acute infection phase. There are indications that prolonged COVID may contribute to autoimmune disease development through mechanisms such as immune hyperactivation, molecular mimicry, and dysregulated cytokine responses. Although this research field is still emerging, growing evidence suggests that SARS-CoV-2 infection may have lasting effects on women's health, highlighting the need for further studies into its underlying mechanisms and long-term clinical outcomes. This review compiles recent findings on the long-term impact of COVID-19 on women's reproductive health and its potential association with autoimmune disorders, particularly MS.},
}
@article {pmid40361909,
year = {2025},
author = {Qiu, S and Hadidchi, R and Vichare, A and Lu, JY and Hou, W and Henry, S and Akalin, E and Duong, TQ},
title = {SARS-CoV-2 Infection Is Associated with an Accelerated eGFR Decline in Kidney Transplant Recipients up to Four Years Post Infection.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
pmid = {40361909},
issn = {2075-4418},
abstract = {Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2. Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan-Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time. Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased -0.98 units/year [-1.50, -0.46]. By contrast, eGFR declined at a significantly greater rate (-1.80 units/year [-2.45, -1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate. Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population.},
}
@article {pmid40361045,
year = {2025},
author = {Shi, J and Lu, R and Tian, Y and Wu, F and Geng, X and Zhai, S and Jia, X and Dang, S and Wang, W},
title = {Prevalence of and factors associated with long COVID among US adults: a nationwide survey.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {1758},
pmid = {40361045},
issn = {1471-2458},
support = {No.2019JQ-555; No.2020JM-408//Natural Science Foundation of Shaanxi Province/ ; No.2019JQ-555; No.2020JM-408//Natural Science Foundation of Shaanxi Province/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; United States/epidemiology ; Female ; Adult ; Male ; Middle Aged ; Prevalence ; Cross-Sectional Studies ; Aged ; Young Adult ; Adolescent ; Behavioral Risk Factor Surveillance System ; Risk Factors ; Socioeconomic Factors ; },
abstract = {BACKGROUND: People with long COVID report prolonged, multisystem involvement and significant disability. This study aimed to determine long COVID prevalence and factors associated with it among US adults using nationally representative data.<br><br>METHODS: This cross-sectional analysis utilized data from 2022 Behavioral Risk Factor Surveillance System survey, a nationally representative telephone survey conducted among noninstitutionalized adults aged&#x2009;&#x2265;&#x2009;18 years residing in the United States. Age-adjusted prevalence of long COVID was calculated using weighted survey analysis. Poisson regression was employed to assess adjusted prevalence ratios (aPRs) associated with long COVID across various demographic, socioeconomic and health-related characteristics.<br><br>RESULTS: Among 390,233 participants, 120,178 reported COVID-19, with 25,582 experiencing long COVID. Age-adjusted prevalence of self-reported COVID-19 and long COVID were estimated at 34.1% (95% CI, 33.7-34.4%) and 7.2% (95% CI, 7.0-7.4%) as of 2022, respectively. Among adults reporting COVID-19, 20.9% (95% CI, 20.5-21.4%) had ever experienced long COVID. An inverted U-shaped association was observed between long COVID risk and age, with the highest prevalence (23.5%) in the 45-54 age group. Long COVID was more prevalent among women (aPR, 1.40 [95% CI, 1.34-1.47]), individuals without a spouse (aPR, 1.06 [95% CI, 1.00-1.13]), uninsured (aPR, 1.16 [95% CI, 1.06-1.27]), and those with a high school education (aPR, 1.17 [95% CI, 1.12-1.23]), cardiovascular disease (aPR, 1.17 [95% CI, 1.09-1.25]), depressive disorder (aPR, 1.41 [95% CI, 1.34-1.48]), chronic obstructive pulmonary disease (aPR, 1.33 [95% CI, 1.24-1.43]), asthma (aPR, 1.28 [95% CI, 1.21-1.35]), and kidney disease (aPR, 1.11 [95% CI, 1.01-1.21]). Long COVID was less prevalent among non-Hispanic Black (aPR, 0.87 [95% CI, 0.81-0.95]), students (aPR, 0.87 [95% CI, 0.76-0.99]) or retired individuals (aPR, 0.89 [95% CI, 0.82-0.98]), and those with household incomes &#x2265;$100,000 (aPR, 0.85 [95% CI, 0.79-0.92]).<br><br>CONCLUSIONS: Long COVID affects 7.2% of US adults, with higher vulnerability among women, middle-aged individuals, White individuals, socioeconomically disadvantaged groups, and those with chronic conditions. These findings underscore the need for targeted public health strategies to address disparities in long COVID burden and support high-risk populations.},
}
@article {pmid40358479,
year = {2025},
author = {Ono, BE and Izaias, JE and Sales, AO and Rodrigues, TS and Nunes, CS and Niec, JF and Rocha, NG and Rocha, HNM and Texeira, GF and Rodrigues, AG and Negrão, CE and Irigoyen, MCC and Colombo, FMC and Nascimento-Filho, AV and De Angelis, K and Santos, RAS and Porcari, AM and Ludwig, KR and Craighead, DH and Rossman, MJ and Moll-Bernardes, R and Seals, DR and Sales, ARK},
title = {Sympathetic neural overdrive, vascular dysfunction, and diminished exercise capacity in patients with long COVID-19: a long-term study of cardiovascular sequelae.},
journal = {American journal of physiology. Regulatory, integrative and comparative physiology},
volume = {329},
number = {1},
pages = {R154-R169},
doi = {10.1152/ajpregu.00055.2025},
pmid = {40358479},
issn = {1522-1490},
support = {E-26/211.526/2021//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro (FAPERJ)/ ; 304697/2020-6//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; K01DK115524//HHS | NIH | All of Us Research Program (AoURP)/ ; //D'Or Institute for Research and Education/ ; },
mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; Female ; Middle Aged ; *Exercise Tolerance ; *Sympathetic Nervous System/physiopathology ; Vascular Stiffness ; *Cardiovascular Diseases/physiopathology/etiology ; SARS-CoV-2 ; Aged ; Adult ; Muscle, Skeletal/innervation ; Post-Acute COVID-19 Syndrome ; },
abstract = {We have recently showed that patients with severe coronavirus disease (COVID) have neurovascular dysfunction, cardiac morphofunctional alterations, and attenuated exercise capacity. However, whether these alterations persist over time is unknown. Here, we tested the hypothesis that patients with long COVID, even 2 yr after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, exhibit sympathetic overdrive, aortic stiffening, endothelium-dependent dysfunction, cardiac morphofunctional changes, and diminished exercise capacity. Eighteen patients with long COVID and 19 well-matched controls were studied. Muscle sympathetic nerve activity (MSNA; microneurography), brachial artery flow-mediated dilation (BAFMD; ultrasound-Doppler), carotid-femoral pulse wave velocity (CFPWV; tonometry), heart rate (HR; electrocardiogram), E-wave/A-wave ratio (E/A ratio), left ventricular ejection fraction and global longitudinal strain (LVEF and LVGLS, respectively; echocardiography), and peak oxygen uptake (peak V̇o2, cardiopulmonary exercise testing) were assessed ∼2 yr after hospital discharge. Circulating angiotensin II (Ang II, mass spectrometry), endothelial cell-derived extracellular vesicles (endothelial cell-derived EVs, flow cytometry), and oxidative stress were also evaluated. Patients with long COVID had higher MSNA, CFPWV, and HR and lower E/A ratio, LVEF, LVGLS, and peak V̇o2 than controls. Endothelial cell-derived EVs and carbonyls were higher in patients with long COVID than controls, whereas superoxide dismutase (SOD) was lower. No difference was observed in Ang II. Peak V̇o2 was inversely associated with MSNA, LVGLS, and carbonyls and directly associated with BAFMD and SOD. Our findings reveal that patients with long COVID, 2 yr after acute illness, exhibit persistent sympathetic overactivation, vascular and cardiac impairments, reduced exercise capacity, and increased endothelial cell-derived EVs and oxidative stress. As such, strategies that can resolve these persistent cardiovascular sequelae are urgently needed.NEW &amp; NOTEWORTHY Patients with long COVID, even 2 yr after SARS-CoV-2 infection, exhibited sympathetic neural overdrive, aortic stiffening, endothelial dysfunction, cardiac morphofunctional changes, diminished aerobic exercise capacity, increased circulating endothelial cell-derived EVs, decreased antioxidant activity, and increased oxidant activity. Moreover, we showed that the reduced aerobic exercise capacity was associated with sympathetic neural outflow, vascular dysfunction, cardiac morphofunctional alterations, and increased circulating oxidative stress.},
}
@article {pmid40357672,
year = {2025},
author = {Durstenfeld, MS and Leonard, D and Pettee Gabriel, K and Barlow, CE and Shuval, K and Priest, R and Pavlovic, A and Radford, NB and Berry, JD and Peluso, MJ and DeFina, LF},
title = {Association of Pre-COVID Fitness With Post-COVID Fitness and Long COVID in the Cooper Center Longitudinal Cohort Study.},
journal = {Journal of the American Heart Association},
volume = {14},
number = {10},
pages = {e040629},
pmid = {40357672},
issn = {2047-9980},
support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K23 HL172699/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Middle Aged ; *COVID-19/physiopathology/epidemiology/complications ; Male ; Female ; Longitudinal Studies ; *Cardiorespiratory Fitness/physiology ; Adult ; Aged ; Texas/epidemiology ; SARS-CoV-2 ; Young Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Cross-sectional studies suggesting that SARS-CoV-2 infection and long COVID are associated with reduced cardiorespiratory fitness (CRF) lack preinfection CRF measures. The objective of this study was to determine the association of SARS-CoV-2 infection and long COVID with change in CRF.<br><br>METHODS: Cooper Center Longitudinal Study is a cohort study based at the Cooper Clinic, a preventive medicine clinic in Dallas, Texas; we included adults ages 20 to 74&#x2009;years old with CRF assessed at least twice between 2017 and 2023. COVID status was defined as "prepandemic" (2 CRF measures pre-2020), "uninfected" (no self-reported COVID), "recovered" (self-reported COVID with symptoms &#x2264;3&#x2009;months), or "long COVID" (self-reported COVID with symptoms >3&#x2009;months). CRF was estimated in metabolic equivalents via a maximal modified Balke treadmill protocol.<br><br>RESULTS: We included 4005 participants (mean age: 51.8&#x2009;years, 26.8% women), of whom, 1666 (41.6%) reported COVID and 80 (4.8% of infected) reported long COVID along with 1826 uninfected and 513 pre-pandemic controls. At baseline, those who later developed long COVID had lower CRF (10.0 metabolic equivalents, 11.1 recovered, 10.7 uninfected, 11.3 prepandemic; P<0.001). All groups exhibited minor decreases in CRF (~0.2 metabolic equivalents; P<0.001 for each). CRF decreased slightly more among the infected (-0.1 metabolic equivalents greater decrease [95% CI, -0.1 to 0.0]; P=0.02) but not by long COVID status (P=0.10).<br><br>CONCLUSIONS: Pre-COVID fitness, on average, is lower among people who developed long COVID. COVID does not greatly accelerate age-related declines in CRF, even among some with long COVID, although few included participants had severely disabling long COVID. Future longitudinal research will clarify if differences in CRF by infection status emerge over longer follow-up.},
}
@article {pmid40355745,
year = {2025},
author = {Khandelwal, Y and Ora, M and Jain, B and Dixit, M and Singh, P and Khan, A and Nath, A and Agarwal, V and Gambhir, S},
title = {Post-COVID-19 lung disease: utility of biochemical and imaging markers in uncovering residual lung inflammation and monitoring anti-inflammatory therapy, a prospective study.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {52},
number = {12},
pages = {4674-4684},
pmid = {40355745},
issn = {1619-7089},
mesh = {Humans ; Male ; Female ; Positron Emission Tomography Computed Tomography ; Middle Aged ; Prospective Studies ; *COVID-19/complications/diagnostic imaging ; Fluorodeoxyglucose F18 ; *Anti-Inflammatory Agents/therapeutic use ; Aged ; Biomarkers/metabolism ; Adult ; Lung/diagnostic imaging ; *Pneumonia/diagnostic imaging/drug therapy ; },
abstract = {PURPOSE: Post-COVID-19 lung disease (PCLD) is a significant concern following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. PCLD encompasses persistent debilitating respiratory symptoms and radiological changes beyond the acute disease phase. It highlights the ongoing search to identify and manage lingering diseases. This prospective study utilizes F18-Fludeoxyglucose (FDG) PET/CT to identify residual inflammatory lung lesions in PCLD. Treatment response was assessed after anti-inflammatory and antifibrotic therapies.<br><br>MATERIALS AND METHODS: Thirty patients post-severe COVID-19 pneumonia enrolled. They underwent baseline [18]F-FDG PET/CT scans to unveil residual lung inflammation lesions on FDG and CT. They received antifibrotic (Pirfenidone) and anti-inflammatory (Methylprednisolone) drugs for 6-12 weeks. They were followed up for clinical, biochemical, and imaging treatment responses.<br><br>RESULTS: Baseline [18]F-FDG PET/CT revealed ongoing lung inflammation in all PCLD (mean SUVmax: 3.8 &#xb1; 2.3 and number of segments: 8&#xb1;3). The mean CT severity score was 17.7 &#xb1; 3.4 with moderate (n&#x2009;=&#x2009;16) or severe (n&#x2009;=&#x2009;14) disease involvement. Mild, moderate, and severe [18]F-FDG PET/CT categories were noted in the 8, 14, and 8 patients, respectively. Following treatment, a PET scan showed a significant decrease in disease extent (segments) and severity (FDG uptake) and an improvement in disease grading on imaging (97% of patients). In PET concordance, there was a significant clinical and radiological improvement with a fall in inflammatory markers (p&#x2009;<&#x2009;0.005). Serum Ferritin and total leukocyte counts were significantly associated with PCLD severity on [18]F-FDG PET/CT(p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: This prospective study identifies and quantifies ongoing significant residual lung inflammation in PCLD on [18]F-FDG PET/CT. Anti-inflammatory and antifibrotic drug therapy led to clinical and radiological improvement. [18]F-FDG PET/CT as a non-invasive biomarker helped manage and follow up PCLD patients.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid40355653,
year = {2025},
author = {Monroy, M and Amster, M and Eagle, J and Zerwas, FK and Keltner, D and López, JE},
title = {Awe reduces depressive symptoms and improves well-being in a randomized-controlled clinical trial.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {16453},
pmid = {40355653},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; *Depression/therapy/psychology ; *COVID-19/psychology ; Middle Aged ; Adult ; Anxiety/psychology/therapy ; *Stress, Psychological/therapy/psychology ; Aged ; SARS-CoV-2 ; Quality of Life ; Mental Health ; },
abstract = {Emerging evidence suggests that experiences of awe benefit health and well-being. The present investigation examined the efficacy of an awe intervention to improve the psychological health-stress, anxiety, depression, and well-being-of patients living with long COVID. The awe intervention, a Randomized-controlled Clinical Trial, was delivered in synchronous online sessions to patients, across the United States (in April 2023), who met the criteria for long COVID. Results revealed significant improvements in psychological health for those in the awe intervention (N = 30), compared to the control group (N = 38): including decreased stress, decreased depression symptoms, and increased well-being. There were no significant differences between groups in anxiety symptoms. Effect sizes ranged from medium to large (d = 0.78-0.96), demonstrating the robustness of these findings. This work is the first to document that awe can have salutary effects on psychological health, such as reducing symptoms of depression. These findings suggest that a brief awe intervention can improve psychological health in people dealing with chronic stress and physical ailments, as in the case of long COVID.Trial registration. The trial is registered at ClinicalTrials.gov (NCT05676008, 09/01/2023).},
}
@article {pmid40354997,
year = {2025},
author = {Duong, KE and Henry, SS and Cabana, MD and Duong, TQ},
title = {Longer-Term Effects of SARS-CoV-2 Infection on Asthma Exacerbation.},
journal = {The journal of allergy and clinical immunology. In practice},
volume = {13},
number = {8},
pages = {2087-2094.e3},
doi = {10.1016/j.jaip.2025.05.010},
pmid = {40354997},
issn = {2213-2201},
mesh = {Humans ; *COVID-19/epidemiology/complications ; *Asthma/epidemiology ; Female ; Male ; Retrospective Studies ; Adult ; Child ; Adolescent ; Middle Aged ; SARS-CoV-2 ; Young Adult ; Child, Preschool ; Disease Progression ; Aged ; Hospitalization/statistics &amp; numerical data ; Risk Factors ; },
abstract = {BACKGROUND: The long-term impact of COVID-19 on asthma exacerbations remains unclear.<br><br>OBJECTIVE: We assessed the future risk of asthma exacerbations after SARS-CoV-2 infection in pediatric and adult patients with asthma.<br><br>METHODS: We conducted a retrospective cohort study of 12,719 patients with asthma with SARS-CoV-2 infection (confirmed by polymerase chain reaction test) and 91,763 without recorded SARS-CoV-2 infection in a large urban health care system (March 1, 2020 to December 31, 2023). After matching for observation time, age, race, and ethnicity, 1,898 children and 8,532 adults were included in each group (with and without COVID-19). Andersen-Gill models adjusted for covariates (eg, allergic rhinitis, gastroesophageal reflux disease, eczema, obesity, unmet social needs) were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for recurrent asthma exacerbations.<br><br>RESULTS: Children who were both hospitalized and not hospitalized for COVID-19 with preexisting asthma had higher exacerbation rates than controls (40.68% and 24.81%, respectively vs 14.70%; P < .001) and increased risk of future exacerbations (aHR = 3.29 [95% CI, 2.27-4.76]; aHR = 1.82 [95% CI, 1.51-2.21]); P < .001). Adults also showed increased asthma exacerbation rates in hospitalized (23.13%) and non-hospitalized (21.49%) individuals compared with controls (10.68%; P < .001). Similarly, adults who were both hospitalized and not hospitalized for COVID-19 had increased risk of future exacerbations (aHR = 2.78 [95% CI, 2.29-3.38]; aHR = 2.13 [95% CI, 1.73-2.62]). Overall, children faced higher risks than adults. Unmet social needs elevated the risk of future exacerbation in children (aHR = 1.36 [95% CI, 1.00-1.86]) and adults (aHR = 1.26 [95% CI, 1.04-1.52]).<br><br>CONCLUSIONS: SARS-CoV-2 infection was associated with a higher cumulative incidence of asthma exacerbations. Patients with unmet social needs were at higher risk of exacerbation. Clinicians should prioritize preventive strategies, trigger reduction, and immunizations for patients with a history of asthma and SARS-CoV-2 infection.},
}
@article {pmid40354936,
year = {2025},
author = {Smith, AB and Greenwood, D and Sivan, M},
title = {Growing Evidence Base on Condition-Specific Patient-Reported Outcome Measures for Long COVID.},
journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research},
volume = {28},
number = {8},
pages = {1300-1301},
doi = {10.1016/j.jval.2024.12.011},
pmid = {40354936},
issn = {1524-4733},
}
@article {pmid40354933,
year = {2026},
author = {Che, W and Guo, S and Wang, Y and Wan, X and Tan, B and Li, H and Alifu, J and Zhu, M and Chen, Z and Li, P and Zhang, L and Zhang, Z and Wang, Y and Huang, X and Wang, X and Zhu, J and Pan, X and Zhang, F and Wang, P and Sui, SF and Zhao, J and Xu, Y and Liu, Z},
title = {SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations.},
journal = {Journal of advanced research},
volume = {80},
number = {},
pages = {743-758},
pmid = {40354933},
issn = {2090-1224},
mesh = {*COVID-19/complications/pathology/virology ; Humans ; *Myocytes, Cardiac/pathology/virology/ultrastructure/metabolism ; *SARS-CoV-2 ; Animals ; Male ; Middle Aged ; Mice ; Female ; *Mitochondria, Heart/pathology ; *Myocarditis/pathology/virology/etiology ; Aged ; Adult ; *Cardiovascular Diseases/pathology/etiology/virology ; *Mitochondria/pathology ; },
abstract = {INTRODUCTION: With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored.<br><br>OBJECTIVES: Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as "Long COVID", which has significantly affected millions globally.<br><br>METHODS: We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, palpitation, chest tightness, and acute myocarditis.<br><br>RESULTS: All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID.<br><br>CONCLUSION: Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.},
}
@article {pmid40354786,
year = {2025},
author = {Kardos, P and Becker, S and Heidenreich, KR and Klimek, L and Köhnlein, T and Labenz, J and Mülleneisen, N and Pfeiffer-Kascha, D and Pink, I and Sitter, H and Trinkmann, F and Worth, H and Winterholler, C and , and , and , and , and , and , and , and , and , },
title = {[Specialist Guidelines of The German Respiratory Society for Diagnosis and Treatment of adult Patients Suffering from Cough].},
journal = {Pneumologie (Stuttgart, Germany)},
volume = {79},
number = {5},
pages = {329-357},
doi = {10.1055/a-2550-3738},
pmid = {40354786},
issn = {1438-8790},
mesh = {Humans ; *Cough/diagnosis/therapy/etiology ; Germany ; Adult ; Societies, Medical ; *Pulmonary Medicine/standards ; Chronic Disease ; },
abstract = {This is the 4[th] edition of the Cough Guidelines of the German Respiratory Society written by respiratory, gastroenterology, ear-nose-throat specialists, including respiratory physiotherapists and speech pathology specialists; importantly, a patient representative was also involved.Compared with earlier versions we used a new methodology: after discussion in the guidelines group, we asked and answered the 12 most important and most frequent "key" questions regarding the clinical practice. The extent of the guideline could thus be significantly reduced.We added a short scientific background to each of the answers including the most recent references. The recommendations and statements were created in consensus and graded as strong, or weak. If sufficient literature was not available, we suggested discussing joint decisions with the patient.The 12 key questions are as follows:- Key question 1: The classification of cough (acute, i. e. up to three weeks duration; chronic, i. e. after 8 weeks duration and subacute in between) did not change, but we added "cough with or without expectoration as an additional classification aspect with therapeutic consequences.- Key question 2: Acute and subacute cough are mostly (but not exclusively) due to the common cold. They are the first or second most frequent symptom prompting patients to seek medical (or pharmacist's) care. Antibiotic therapy is strongly discouraged for common cold- Key question 3: We defined "Red flags" for mandatory immediate diagnostic for acute cough, which usually does not require such diagnostic procedures- Key question 4: Chronic cough overview of the most common causes for- Key question 5: Cough in acute SARS-CoV-2 infection and in long COVID - Key question 6: Refractory chronic cough and idiopathic chronic cough, two recently established entities were explained more in detail- Key question 7: To upper airway cough syndrome - Key question 8: Gastro-oesophageal-reflux-related cough - Key question 9: Cough-variant asthma and non-asthmatic eosinophilic bronchitis - Key question 10: Overview of drugs causing cough - Key question 11: Basic and personalized (due to the individual history) diagnostic procedures for patients with cough- Key question 12: Physiotherapy, speech therapy and pharmacotherapy for cough.},
}
@article {pmid40354184,
year = {2025},
author = {Hawkins, KL and Dandachi, D and Verzani, Z and Brannock, MD and Lewis, C and Abedian, S and Jaferian, S and Wuller, S and Truong, J and Witvliet, MG and Dymond, G and Mehta, HB and Patel, PB and Hill, E and Weiner, MG and Carton, TW and Kaushal, R and Feuerriegel, E and Tran, HG and Marks, K and Oliveira, CR and Gardner, EM and Ofotokun, I and Gulick, RM and Erlandson, KM},
title = {HIV Infection and Long COVID: A RECOVER Program, Electronic Health Record-Based Cohort Study.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {81},
number = {3},
pages = {427-438},
pmid = {40354184},
issn = {1537-6591},
support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2HL161847/NH/NIH HHS/United States ; K24 AGE082527/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *HIV Infections/epidemiology/complications ; Male ; *COVID-19/epidemiology/complications ; Female ; Electronic Health Records ; Middle Aged ; Adult ; Cohort Studies ; SARS-CoV-2 ; Aged ; Risk Factors ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: People with human immunodeficiency virus (HIV) may be at increased risk for long COVID after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association between HIV and long COVID in 2 large electronic health record databases.<br><br>METHODS: Using data from the Patient-Centered Clinical Research Network (PCORnet) and the National Clinical Cohort Collaborative (N3C) from 1 January 2018 to 30 April 2024, our analytic sample included individuals aged &#x2265;21 years with SARS-CoV-2. All individuals were classified as having HIV or not. We estimated the adjusted odds ratio (aOR) of long COVID by HIV status using logistic regression. Multivariable models controlled for potential associated factors and used 2 cohort definitions: a computed phenotype definition or ICD-10 code-based definition.<br><br>RESULTS: We included 1 369 896 patients from PCORnet (11 964 with and 1 357 932 without HIV) and 3 312 355 patients from N3C (23 931 with and 3 288 424 without HIV). Using the computed phenotype definition of long COVID, we noted a small, but significant, increase in odds of developing long COVID among people with compared to those without HIV (PCORnet: aOR, 1.09 [95% confidence interval {CI},
1.04-1.14]; N3C: aOR, 1.18 [95% CI, 1.13-1.23]). Using the ICD-10 definition of long COVID, there was no association between HIV and long COVID (PCORnet: aOR, 1.01 [95% CI, .88-1.16]; N3C: aOR, 1.07 [95% CI, .97-1.18]).<br><br>CONCLUSIONS: In this large multicenter study, people with HIV had a modestly increased risk of long COVID when defined by a computed phenotype, but not when using ICD-10 codes. These findings suggest that long COVID may be underrecognized in people with HIV and underscore challenges in diagnosing long COVID in populations with baseline chronic conditions.},
}
@article {pmid40353707,
year = {2025},
author = {Panagea, E and Messinis, L and Patrikelis, P and Malefaki, S and Petri, MC and Nasios, G and Liontos, A and Biros, D and Kosmidis, MH and Milionis, H},
title = {Persistent neuropsychological deficits in recovered COVID-19 patients: Correlations with disease biomarkers.},
journal = {Applied neuropsychology. Adult},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/23279095.2025.2502871},
pmid = {40353707},
issn = {2327-9109},
abstract = {OBJECTIVE: Cognitive impairment, including deficits in attention, memory, executive function, and processing speed, is common in post-COVID-19 conditions, though language performance remains less studied. The present study examined the long-term effects of COVID-19 condition on cognition and language - communication, and its associations with disease severity, Body Mass Index (BMI), inflammatory markers, and quality of life.<br><br>METHOD: Nighty eight Greek participants under 65&#x2009;years of age were recruited for this study. Forty-seven participants were allocated in the COVID-19 group and 51 served as cognitively healthy controls. The COVID-19 group was categorized by disease severity and long COVID status. Assessments occurred 12&#x2009;weeks post-infection, with 12 patients reevaluated after another 12&#x2009;weeks. Neurocognitive tests included ABCD-II, verbal fluency, CCT, SDMT, and Euro QoL EQ-5D. Blood samples were analyzed for inflammatory markers.<br><br>RESULTS: Covid-19 survivors experienced significant cognitive deficits compared to healthy controls, particularly in processing speed, memory, and verbal fluency. Long COVID patients showed notably lower scores in processing speed and QoL, compared to those without Long COVID. However, no significant differences were observed between groups on episodic memory and executive functions tasks. Cognitive deficits were associated with biomarkers such as d-dimers and C-Reactive protein, with elevated d-dimers linked to poorer performance on generative drawing and cognitive flexibility. Higher education served as a protective factor, and was associated with higher scores in tasks such as story retelling, confrontation naming, generative drawing and reading comprehension. Older age and higher Body Mass Index were associated with poorer cognitive performance, especially on processing speed. Sex appears to influence language comprehension outcomes, with males exhibiting enhanced performance on the reading comprehension-sentence task. Disease severity negatively affected performance on the Symbol Digit Modalities Test and generative naming, indicating that greater severity was linked to poorer outcomes in these domains. Follow-up evaluations of recovered COVID-19 patients revealed significant improvements in processing speed and recall, suggesting partial recovery in these areas, although some deficits persisted over time.<br><br>CONCLUSION: The study supports findings that the prolonged effects of COVID-19 markedly impaired neurocognitive functions in recovering patients, especially those with severe or long COVID syndrome. Moreover, while several cognitive domains may improve over time, many other domains remain impaired and vulnerable.},
}
@article {pmid40352471,
year = {2025},
author = {Almoliky, MA and Alsaif, B and Saleh, KA and Alkubati, SA and Hassan, SU and Algahtani, FD and Aldhmadi, BKM and Assaggaf, HM and Alzain, MA},
title = {Long COVID Symptoms and Five Dimensions of HRQoL: A Retrospective Regional Study of Patients Recovered from COVID-19 Infection in Saudi Arabia.},
journal = {International journal of general medicine},
volume = {18},
number = {},
pages = {2401-2416},
pmid = {40352471},
issn = {1178-7074},
abstract = {BACKGROUND/AIM: 10-20% of people infected with the coronavirus infection have long COVID symptoms, therefore, current research is the first regional assessment in Saudi Arabia to determine the relationship between long-term health complaints of COVID-19 survivors and health-related quality of life (HRQoL).<br><br>METHODS: The study population comprised COVID-19 infection cases registered in the Ha'il region of Saudi Arabia from the beginning of the COVID-19 pandemic until September 2022. A retrospective research design was employed, and 295 participants completed a self-report questionnaire to assess long COVID symptoms and the Arabic version of the European 5-Dimensional Quality of Life (EQ-5D). Multiple linear regression was used to evaluate the predictive role of long COVID symptoms on the HRQoL of patients by choosing (p-value < 0.05).<br><br>RESULTS: The mean (SD) age of the participants was 38 years, (67.1%) were male and (58.6%) were married. On the long COVID-19 symptoms, the highest mean values were fatigue (M=2.3; 95% CI 2.1-2.4) followed by headache (M=2.1; 95% CI 2.0-2.3) and persistent cough (M=1.9; 95% CI 1.8-2.1). Findings show that HRQoL was problematic in domains of pain/discomfort as depicted by a highest mean score on this domain (M=4.24; 95% CI 4.14-4.33) followed by anxiety/depression (M=4.17: 95% CI 4.08-4.27). Multiple regression analysis showed that marital status (p=0.05), irregular exercise (p<0.01), duration of hospitalization (p<0.01), and oxygen therapy (p<0.05) were the independent background factors affecting HRQoL post-COVID-19. Among the long-COVID-19 symptoms, fatigue (p=0.05), persistent cough (p=0.001), dyspnea (p=0.02), and sexual dysfunction (p<0.001) were the independent factors that impacted the HRQoL after controlling for background variables.<br><br>CONCLUSION: The study has significant implications for Saudi Arabia's Health Sector Transformation Program that could achieve its goals of human centric care and patient satisfaction though addressing the negative impacts of specific long-COVID symptoms such as fatigue, persistent cough, dyspnea and sexual dysfunction and improving the HRQoL in domains of pain/discomfort and anxiety/depression.},
}
@article {pmid40352436,
year = {2025},
author = {Kok, LHJ and Gu, JT and Kung, JTY and Liang, SS and Gonzalez, PC and Toh, FM and Sin, E and Fong, KNK},
title = {User experiences of patients with post-acute COVID-19 syndrome receiving occupational therapy telerehabilitation.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1551631},
pmid = {40352436},
issn = {1662-5161},
abstract = {BACKGROUND: Patients with post-acute COVID-19 syndrome, also referred to as "long COVID," may face persistent physical, cognitive and psychosocial symptoms which can be challenging to manage given the strict social distancing measures imposed during the pandemic. Telerehabilitation (TR) became increasingly common during COVID-19 pandemic and has been applied to post-acute COVID-19 conditions in previous clinical studies, and it was reported that patients' symptoms were alleviated and their overall health improved. This study examined the usability and acceptability of TR by occupational therapists delivered for patients suffering from post-acute COVID-19 in Hong Kong.<br><br>METHODS: In this mixed-methods usability study, participants rated items on the System Usability Scale (SUS) and completed a semi-structured questionnaire via audio-recorded telephone calls. Descriptive data were used to summarize the quantitative data, and thematic analysis was applied to analyze the qualitative data.<br><br>RESULTS: Twelve participants (mean age 56.5 years) who had completed a 6-week TR program via the Caspar Health system were recruited for the study. A median SUS score of 56.25 was reported for its usability, despite 83% of the participants viewed the TR system as fairly acceptable. Four themes, namely perception of using the TR system - performance expectancy of TR, other psychosocial and environmental factors, and intention to use TR, were generated on the basis of the participants' interviews. Most participants reported their willingness to continue using TR and that they would recommend it to other patients.<br><br>CONCLUSION: Most of the participants were receptive to TR and perceived health benefits from its use. Future research could consider integrating the perspectives of both occupational therapists and patients to generate a more comprehensive understanding of the facilitators of and the barriers to TR for patients who experience long COVID.},
}
@article {pmid40351462,
year = {2025},
author = {Rezende, AG and Valente, J and Goulart, CDL and Facioli, F and Maia, B and Mwangi, VI and Bonilla, H and Franssen, FME and do Amaral, CMSSB and Motta, TJPS and Alexandre, M and Ferreira, LCL and Cipriano Junior, G and Arêas, GPT and Almeida-Val, F},
title = {Does long COVID in people living with HIV resemble the functional phenotype of non-HIV individuals who had moderate or severe acute COVID-19? A retrospective cross-sectional study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1533009},
pmid = {40351462},
issn = {2296-858X},
abstract = {INTRODUCTION: It has been postulated that individuals with long COVID have reduced exercise capacity, just as people living with HIV (PLWH), although having even lower exercise capacity. The extent to which long COVID in PLWH resembles long COVID in individuals who presented different COVID-19 phenotypes is unknown, so we aimed to determine if the long COVID profile in PLWH resembled the symptoms experienced by individuals with long COVID following mild/moderate or severe acute COVID-19, 2 years after the initial disease.<br><br>MATERIAL AND METHODS: A pulmonary function test and a 6-min walk test (6MWT) were performed on adult individuals with PACS (Post-Acute COVID Syndrome) in 3 groups: COVID-19+PLWH (plwHCOV), mild/moderate COVID-19 (mmCOV); severe COVID-19 (seCOV).<br><br>RESULTS: Sixty three individuals were included: plwHCOV (n = 12), mmCOV (n = 33) and seCOV (n = 18). Across all groups, males were predominant. BMI was 25 &#xb1; 3, 28 &#xb1; 4, and 32 &#xb1; 7 kg/m[2] in plwHCOV, mmCOV, and seCOV, respectively (p = 0.003). The plwHCOV walked 545 m (&#xb1;93) at the 6MWT, which was comparable to the mmCOV group (555 m &#xb1; 63) but significantly higher than the seCOV group (435 m &#xb1; 84) (p < 0.0001). The plwHCOV group had worse forced expiratory volume in 1st second (FEV1%, 80 &#xb1; 12) (p < 0.0001), forced vital capacity (FVC%, 83 &#xb1; 11) (p = 0.002) and FEV1/FVC (0.80 &#xb1; 0.1, p = 0.004) when compared to the seCOV group. Interestingly, PLWH had comparable 6MWT, FEV1, FVC, and FEV1/FVC results as mmCOV.<br><br>CONCLUSION: Our results indicate that even 2 years post-COVID-19 infection, PLWH exhibits significantly decreased spirometry compared to the seCOV group. Despite this lung function impairment, their functional capacity was similar to individuals with PACS following mild/moderate COVID-19.},
}
@article {pmid40351239,
year = {2025},
author = {Iijima, H and Funaki, T and Kubota, M},
title = {Long-COVID in children and their parents: A prospective cohort study.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {67},
number = {1},
pages = {e70042},
pmid = {40351239},
issn = {1442-200X},
support = {JP22K02483//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/complications ; Child ; *Quality of Life ; Prospective Studies ; Child, Preschool ; Prevalence ; Adolescent ; Japan/epidemiology ; Risk Factors ; *Parents ; Infant ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; SARS-CoV-2 ; Sleep Wake Disorders/epidemiology ; },
abstract = {BACKGROUND: Long-COVID is a significant global health concern, regardless of age. However, few reports have longitudinally evaluated the characteristics, prevalence, and risk factors of long-COVID in children.<br><br>METHODS: Participants were Japanese children younger than 18&#x2009;years hospitalized for COVID-19 between November 2021 and October 2022, along with their COVID-19 affected parents. During hospitalization and at 1-, 3-, and 6-month follow-ups, participants completed age-appropriate questionnaires on long-COVID symptoms. The quality of life (QOL) score was assessed in children older than 2&#x2009;years. The prevalence of long-COVID symptoms by age group was compared. Multivariable logistic regression analysis was conducted to investigate risk factors affecting long-COVID. Analysis of covariance adjusted for potential confounders was conducted to determine which symptoms affect QOL score.<br><br>RESULTS: Of 108 children enrolled, the prevalence of long-COVID was 44.9%, 37.8%, and 22.8% at 1, 3, and 6&#x2009;months, respectively, after SARS-CoV-2 infection. There were no specific risk factors for long-COVID. Cough, fatigue, and sleep disturbance were the most common long-COVID symptoms, with sleep disturbance associated with a change in lower QOL score from admission at all three follow-ups (mean difference 9.25, 20.15, and 19.81; 95% CI, 1.58-16.91, 3.38-36.92, and 5.51-34.11). The prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms among 0-6&#x2009;years was significantly lower than among 7-17&#x2009;years and parents; there was no significant difference between 7 and 17&#x2009;years and parents.<br><br>CONCLUSION: Even 6&#x2009;months after SARS-CoV-2 infection, 22.8% of pediatric patients still had long-COVID symptoms. Some of these symptoms were similar to those of ME/CFS, potentially affecting children's QOL.},
}
@article {pmid40351205,
year = {2025},
author = {Sullivan, DL and Goddard, K and Kurth, NK and Hall, JP},
title = {"I'm in Hell …": Experiences of Unmet Health Care Needs Among People with Pre-Existing Disability and Long COVID.},
journal = {Journal of health care for the poor and underserved},
volume = {36},
number = {2},
pages = {572-589},
pmid = {40351205},
issn = {1548-6869},
support = {90IFRE0050/ACL/ACL HHS/United States ; },
mesh = {Humans ; *COVID-19/epidemiology/therapy ; *Persons with Disabilities/statistics &amp; numerical data ; Female ; Male ; Middle Aged ; Adult ; *Health Services Accessibility/statistics &amp; numerical data ; *Health Services Needs and Demand/statistics &amp; numerical data ; United States/epidemiology ; Aged ; Young Adult ; Surveys and Questionnaires ; Adolescent ; },
abstract = {The unmet health care needs of people with pre-existing disabilities who have long COVID are understudied. During the COVID-19 pandemic, people with disabilities experienced barriers to accessing care and supplies needed to prevent and treat COVID-19. Once they had contracted COVID-19, people with disabilities were more likely to develop long COVID compared with people without disabilities. Using the 2022 National Survey on Health and Disability, this study aimed to compare how unmet health care needs differ among people with pre-existing disabilities with and without long COVID. We examined bivariate associations between unmet health care needs and respondents' demographic characteristics and responses to open-ended survey questions. About 73% of respondents with long COVID reported unmet health care needs compared with 62.6% of respondents without long COVID. Four key themes emerge from open-ended responses: exacerbation of existing disability, navigating the health care system, gaslighting by health care providers, and financial burdens.},
}
@article {pmid40350710,
year = {2025},
author = {Juliet S, D and J, B},
title = {Prescriptive analytics decision-making system for cardiovascular disease prediction in long COVID patients using advanced reinforcement learning algorithms.},
journal = {Journal of X-ray science and technology},
volume = {33},
number = {5},
pages = {879-900},
doi = {10.1177/08953996251335115},
pmid = {40350710},
issn = {1095-9114},
mesh = {Humans ; *COVID-19/complications ; *Cardiovascular Diseases/diagnosis ; Algorithms ; SARS-CoV-2 ; Machine Learning ; },
abstract = {In recent years Covid-19 impact is causing unprecedented difficulties worldwide, affecting lifestyle choices. The post-pandemic era has made this even more critical.COVID-19 triggers widespread inflammation throughout the body, potentially causing damage to the heart and other vital organs. Mortality data from COVID-19 clearly show that the highest death rates occur in individuals with chronic conditions, such as diabetes, pneumonia, cardiovascular disease (CVD), and acute renal failure.CVD is a particular concern in the medical field. The early detection of CVD remains a significant challenge, as early identification can prompt lifestyle changes and ensure appropriate medical interventions when needed. Individuals with CVD are at an increased risk for heart attack and other serious complications. There is a limited amount of data available to study the effects of COVID-19 on CVD in COVID-19 patients. However, it is essential to monitor these patients to ensure full recovery without complications. The proposed system is specifically designed for individuals experiencing prolonged symptoms following a COVID-19 infection, commonly referred to as long COVID patients. This research introduces a novel Decision-Making System for CVD Prediction, utilizing an improved dual-attention residual bi-directional gated recurrent neural network unit (DA-ResBiGRU) algorithm with AI-Biruni Earth Radius Optimization (ABER). The proposed system employs state-of-the-art predictive algorithms and real-time monitoring to assess individual patient risk profiles accurately. This research addresses the critical need for personalized risk assessment in patients with long-term COVID, aiming to assist healthcare providers in timely and targeted interventions. By analyzing intricate patterns in patient data, the decision-making system enhances the precision of CVD prediction. Additionally, the system's adaptive nature allows it to continuously learn from new patient data, ensuring that its predictions remain up-to-date and reflective of the evolving understanding of long COVID-related cardiovascular risks. The simulation findings of this research highlight the potential of the proposed algorithm to be integrated into clinical decision-making, helping healthcare professionals identify high-risk patients more effectively. The proposed method outperformed existing algorithms, such as Deep Neural Network (DNN), Long short-term memory (LSTM), Inception-v3, Xception, and MobileNetV2, achieving the highest accuracy (97.88%), sensitivity (95.50%), specificity (94.29%), precision (96.68%), and F-measure (95.85%).},
}
@article {pmid40349730,
year = {2025},
author = {Peter, RS and Sedelmaier, L and Nieters, A and Brockmann, SO and Göpel, S and Merle, U and Steinacker, JM and Kräusslich, HG and Rothenbacher, D and Kern, WV and , },
title = {Symptom burden and post-COVID-19 syndrome 24 months following SARS-CoV-2 infection: Longitudinal population-based study.},
journal = {The Journal of infection},
volume = {90},
number = {6},
pages = {106500},
doi = {10.1016/j.jinf.2025.106500},
pmid = {40349730},
issn = {1532-2742},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Male ; Middle Aged ; Longitudinal Studies ; Germany/epidemiology ; Adult ; Fatigue/epidemiology ; SARS-CoV-2 ; Prevalence ; Post-Acute COVID-19 Syndrome ; Aged ; Cost of Illness ; Symptom Burden ; },
abstract = {OBJECTIVES: To describe the symptom burden and associated impairment two years after SARS-CoV-2 index infection.<br><br>METHODS: Participants of an earlier large population-based survey in Southwestern Germany (August-September 2021) were contacted again in November 2023. We calculated the prevalences of suspected PCS and specific symptom clusters at both time points and investigated factors for their resolution or emergence.<br><br>RESULTS: A total of 6635 subjects (mean age 46.6 years, 60.9% females) participated in the follow-up. Between baseline and follow-up (median 8.7 and 23.9 months after infection) there were only small changes in the point prevalence of post-COVID-19 syndrome (PCS) (29.9% versus 31.2%) or defined symptom clusters such as fatigue (23.8% versus 22.0%), neurocognitive impairment (15.8% versus 17.3%), or chest symptoms (14.4% versus 13.7%). Probabilities of resolution were often similar to probabilities of emergence, e.g. fatigue symptoms resolved in 9.8% of participants but emerged in 8.0%. Consistent predictors for emerging symptom clusters were female sex, obesity and medical treatment of the acute infection. The six main symptom clusters together explained 45% (physical domain) and 29% (mental domain) of the variance in health-related quality of life (hrQoL).<br><br>CONCLUSIONS: We found a remaining high symptom prevalence two years after SARS-CoV-2 infection, but symptoms present nine months after the&#xa0;index infection often resolved, which was associated with increasing hrQoL. Remarkably, a considerable portion of symptoms newly emerged, of which only a few could be attributed to reported SARS-CoV-2 reinfection.},
}
@article {pmid40349646,
year = {2025},
author = {Yagi, K and Kondo, M and Terai, H and Asakura, T and Kimura, R and Takemura, R and Tanaka, H and Ohgino, K and Masaki, K and Namkoong, H and Chubachi, S and Miyata, J and Kawada, I and Kaido, T and Mashimo, S and Kobayashi, K and Hirano, T and Lee, H and Sugihara, K and Omori, N and Watase, M and Mochimaru, T and Satomi, R and Makino, Y and Inoue, T and Sayama, K and Oyamada, Y and Ishii, M and Sato, Y and Fukunaga, K},
title = {Impact of long COVID on the health-related quality of life of Japanese patients: A prospective nationwide cohort study.},
journal = {Respiratory investigation},
volume = {63},
number = {4},
pages = {610-616},
doi = {10.1016/j.resinv.2025.05.001},
pmid = {40349646},
issn = {2212-5353},
mesh = {Humans ; *Quality of Life ; *COVID-19/complications/psychology/epidemiology/physiopathology ; Prospective Studies ; Male ; Female ; Japan/epidemiology ; Middle Aged ; Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Fatigue/etiology ; Time Factors ; East Asian People ; },
abstract = {BACKGROUND: Various prolonged systemic symptoms, forming the long coronavirus disease (COVID), have been observed in patients who have recovered from the acute phase of COVID-19. Although previous studies have reported that COVID-19 impacts health-related quality of life (HRQoL), the associations of long COVID symptoms and clinical characteristics with HRQoL remain unclear. This study aimed to clarify these associations using nationwide Japanese epidemiological data.<br><br>METHODS: A prospective nationwide cohort study was conducted on patients with COVID-19 between January 2020 and February 2021&#xa0;at 26 participating medical institutions in Japan. Various long COVID symptoms and HRQoL scores at 3, 6, and 12 months following diagnosis were collected from 986 participants. Generalized estimating equations (GEE) were used to explore the association between HRQoL scores evaluated using the short form-8 (SF-8), long COVID symptoms, and baseline clinical characteristics.<br><br>RESULTS: Patients who had one long COVID symptom showed a significantly lower physical component summary score (PCS) and mental component summary score (MCS) compared with those without any symptoms at all time points after diagnosis. GEE revealed that long COVID symptoms, including dyspnea, fatigue, headache, and muscle weakness, were significantly associated with worse PCS, whereas poor concentration, sleep disorders, fatigue, and headache were significantly associated with worse MCS. Severity-related baseline parameters for patients with COVID-19 were significantly associated with worse PCS scores, although these factors were not significantly associated with worse MCS scores.<br><br>CONCLUSIONS: Long COVID symptoms were associated with lower physical and mental HRQoL. Severe outcomes of COVID-19 impacted PCS but not MCS.},
}
@article {pmid40346201,
year = {2025},
author = {Grady, CB and Bhattacharjee, B and Silva, J and Jaycox, J and Lee, LW and Silva Monteiro, V and Sawano, M and Massey, D and Caraballo, C and Gehlhausen, JR and Tabachnikova, A and Mao, T and Lucas, C and Peña-Hernandez, MA and Xu, L and Tzeng, TJ and Takahashi, T and Herrin, J and Güthe, DB and Akrami, A and Assaf, G and Davis, H and Harris, K and McCorkell, L and Schulz, WL and Griffin, D and Wei, H and Ring, AM and Guan, L and Dela Cruz, C and Krumholz, HM and Iwasaki, A},
title = {Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {163},
pmid = {40346201},
issn = {2730-664X},
support = {R01 AI157488/AI/NIAID NIH HHS/United States ; U01 FD005938/FD/FDA HHS/United States ; },
abstract = {BACKGROUND: The symptomatic and immune responses to COVID-19 vaccination of people with Long COVID are poorly characterized.<br><br>METHODS: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-na&#xef;ve individuals with Long COVID. Surveys were administered before vaccination and at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination.<br><br>RESULTS: At 12 weeks post-vaccination, self-reported improved health is seen in 10 out of 16 participants, 3 have no change, and 3 have worse health although 2 report transient improvement after vaccination. One participant reporting worse health was hospitalized twice with chest pain (after each dose). Symptom outcomes are most associated with plasma biosignatures. Higher baseline sIL-6R is associated with symptom improvement, and stably elevated levels of IFN-&#x3b2; and CNTF are associated with no improvement. Significant elevation in SARS-CoV-2-specific TCRs and spike protein-specific IgG are observed at 6 and 12 weeks after vaccination. No changes in reactivities are observed against herpes viruses and self-antigens.<br><br>CONCLUSIONS: In this study of 16 people with Long COVID, vaccination is associated with increased SARS-CoV-2 spike protein-specific IgG and T cell expansion in most participants. Specific immune features are associated with symptom change after vaccination and most participants experience improved health or no change following vaccination.},
}
@article {pmid40343901,
year = {2025},
author = {Gierthmuehlen, M and Gierthmuehlen, PC},
title = {COVIVA: Effect of transcutaneous auricular vagal nerve stimulation on fatigue-syndrome in patients with Long Covid - A placebo-controlled pilot study protocol.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0315606},
pmid = {40343901},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/complications ; Pilot Projects ; *Vagus Nerve Stimulation/methods ; Quality of Life ; *Fatigue/therapy/etiology ; Adult ; Male ; Female ; SARS-CoV-2 ; Middle Aged ; Post-Acute COVID-19 Syndrome ; *Transcutaneous Electric Nerve Stimulation/methods ; },
abstract = {BACKGROUND: Up to 80% of patients who develop coronavirus disease-2019 (Covid-19) infection subsequently experience long covid/post-covid syndrome. The World Health Organization (WHO) has estimated that >770 million patients have been infected with Covid-19 globally. Even if only 10% of these patients develop long covid, > 75 million patients will suffer for a long period. Among the various symptoms of post-covid syndrome, fatigue is common, affecting up to 60% of the patients. As observed in other viral infections, elevated levels of inflammatory cytokines may play a role. Transcutaneous auricular vagal nerve stimulation (taVNS) is a noninvasive method that modulates the immune system via the central nervous system and has shown promising effects in autoimmune diseases and improving fatigue. In this pilot study, we investigated the feasibility of daily taVNS in patients with long covid-related fatigue. Additionally, the effects of taVNS on fatigue and quality of life will be analyzed.<br><br>METHODS: A total of 45 adult patients with long covid associated fatigue syndrome will be enrolled in this study, and will be randomized to the above-threshold-stimulation, below-threshold-stimulation, or sham-stimulation arms, after being informed that they will feel the stimulation. The above-threshold-group will receive a 4-week-long left-sided cymba conchae taVNS with 25 Hz, 250 &#xb5;s pulse width 28s/32s on/off paradigm for 4&#x2009;h throughout the day. The below-threshold group will receive stimulation below the sensational threshold, whereas the sham group will receive no stimulation following application of a non-functional electrode. The daily stimulation protocol will be recorded either manually or using the provided app. Three well-established questionnaires, the Multidimensional-Fatigue-Inventory-20, Short-Form-36, and Beck-Depression-Inventory, and the newly established Post-Covid-Syndrome-Score will be completed both before and after 4 weeks of stimulation.<br><br>DISCUSSION: The primary endpoint has been set as the patients' average daily stimulation time after 4 weeks, while secondary endpoints include the effects of taVNS on fatigue and Quality of Live (QoL). As a non-invasive treatment option, taVNS may be a notable alternative for patients with post-covid related fatigue.<br><br>TRIAL REGISTRATION: This study was approved by the local ethics committee (23/7798) and registered (DRKS00031974) (see supporting information files).<br><br>ETHICS &amp; DISSEMINATION: The ethical justifiability of this study was supported by prior research demonstrating the safety of taVNS. Patients will be recruited by general practitioners, and written informed consent will be obtained. All data will be pseudonymized for collection and storage. The study results will be published in peer-reviewed journals with the aim of providing evidence of the potential of taVNS in long covid management. The study will be conducted in accordance with the principles of the Declaration of Helsinki.},
}
@article {pmid40343325,
year = {2025},
author = {Opielinski, LE and Uhrich, TD and Haischer, MH and Beilfuss, RN and Mirkes Clark, LM and Kroner, KM and Bollaert, RE and Danduran, MJ and Piacentine, LB and Hoeger Bement, M and Papanek, PE and Hunter, SK},
title = {COVID-19 and the impact of physical activity on persistent symptoms.},
journal = {Frontiers in sports and active living},
volume = {7},
number = {},
pages = {1560023},
pmid = {40343325},
issn = {2624-9367},
abstract = {INTRODUCTION: Physical activity is protective against chronic disease but whether activity is associated with persistent symptoms in non-hospitalized coronavirus disease 2019 (COVID-19) survivors is unknown. The purpose of the study was to determine the impact of the COVID-19 pandemic on physical activity levels and the influence of physical activity on acute COVID-19 and long COVID symptoms in non-hospitalized COVID-19 survivors.<br><br>METHODS: In total, 64 non-hospitalized COVID-19 survivors (45 female participants, 40&#x2009;&#xb1;&#x2009;18&#x2005;years) were assessed for activity levels, body composition, and symptoms of COVID-19 8.5&#x2009;&#xb1;&#x2009;4.7&#x2005;months post-infection and categorized into two groups: (1) persistent symptoms and (2) no symptoms at the time of testing. Furthermore, 43 of the 64 participants (28 female participants, 46&#x2009;&#xb1;&#x2009;18&#x2005;years) completed a follow-up questionnaire online 51.0&#x2009;&#xb1;&#x2009;39.7&#x2005;months (4.25&#x2005;years) post-infection. A subset of 22 COVID-19 survivors (16 female participants, 35&#x2009;&#xb1;&#x2009;16&#x2005;years) were matched for age, sex, and body mass index with healthy controls. Physical activity was quantified using (1) self-reported questionnaire (International Physical Activity Questionnaire; IPAQ-SF) at three time periods; prior to COVID-19 infection, at the time of laboratory testing (8.5&#x2009;&#xb1;&#x2009;4.7&#x2005;months after infection), and during an online follow-up (51.0&#x2009;&#xb1;&#x2009;39.7&#x2005;months, i.e., 4.25&#x2005;years after infection); and (2) 7&#x2005;days of wearing an ActiGraph accelerometer following laboratory testing.<br><br>RESULTS: Physical activity (IPAQ-SF) declined in COVID-19 survivors from pre-COVID-19 infection to 8.5&#x2009;&#xb1;&#x2009;4.7&#x2005;months after infection [3,656 vs. 2,656&#x2005;metabolic equivalent of task (MET)&#x2005;min/week, 27% decrease, p&#x2009;<&#x2009;0.001, n&#x2009;=&#x2009;64] and rebounded to levels similar to pre-COVID-19 infection at 4.25&#x2005;years after infection (p&#x2009;=&#x2009;0.068, n&#x2009;=&#x2009;43). Activity levels quantified with accelerometry did not differ between COVID-19 survivors and controls. However, COVID-19 survivors who reported persistent symptoms 8.5&#x2005;months after infection (n&#x2009;=&#x2009;29) engaged in less moderate-vigorous physical activity and steps/day than those without persistent symptoms (n&#x2009;=&#x2009;27) (37 vs. 49&#x2005;MET&#x2005;min/day, p&#x2009;=&#x2009;0.014 and 7,915 vs. 9,540 steps/day, p&#x2009;=&#x2009;0.014).<br><br>DISCUSSION: Both COVID-19 survivors and matched controls reported reductions in physical activity indicating that lower levels of activity were likely due to the pandemic rather than COVID-19 infection alone. However, those who were most affected by COVID-19 infection with persistent symptoms had the greatest reductions in physical activity, even at &#x223c;8&#x2005;months and &#x223c;4&#x2005;years post-infection.},
}
@article {pmid40343154,
year = {2025},
author = {Tsui, CM and Chan, SC and Lam, LF and Lam, MJ and Lee, TY and Leung, K},
title = {Impact of Long COVID symptoms on individuals in Hong Kong: Implications for occupational therapy practices.},
journal = {The British journal of occupational therapy},
volume = {88},
number = {3},
pages = {158-165},
pmid = {40343154},
issn = {1477-6006},
abstract = {INTRODUCTION: From occupational therapy perspective, this study investigates the nature and impact of Long COVID symptoms on individuals in Hong Kong according to their gender, age, and occupation and to understand their treatment needs.<br><br>METHOD: A total of 193 participants with an acute COVID-19 episode 3&#x2009;months ago and having recovered from it who were experiencing subjective symptoms of Long COVID were recruited through snowball sampling from local COVID-19 support groups and healthcare facilities to participate in a cross-sectional design via an online survey assessing their symptoms and the impact on daily activities, and exploring their treatment preferences.<br><br>FINDINGS: Respiratory, systemic, sleep, and cognitive symptoms were found to be the most prevalent, with significant variations in symptom severity and impact on daily life across different age and occupational status groups. The treatment preference was quite strongly inclined to traditional Chinese medicine.<br><br>CONCLUSION: This study has uncovered the critical and yet recognized roles of occupational therapy in managing Long COVID impact by identifying the potential gaps of occupational therapy in its management and calling for advocating promotion in the community and interdisciplinary collaboration with traditional Chinese medicine. Implications about occupational therapy management and the healthcare policies for tailoring treatment programs are discussed.},
}
@article {pmid40343014,
year = {2025},
author = {Ongaya, A and Cardenas, AR and Shiluli, C and Ramos, LB and Senador, LC and Flores, JA and Kanoi, BN and Reijneveld, JF and Ruvalcaba, A and Perez, D and Waiganjo, P and Lindestam Arlehamn, CS and Henrich, TJ and Peluso, MJ and Leon, SR and Gitaka, J and Suliman, S},
title = {Prevalence of Long COVID in Mycobacterium tuberculosis-exposed Groups in Peru and Kenya.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40343014},
support = {R01 AI169534/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Long COVID (LC), also referred to as post-COVID condition, refers to new or worsening symptoms lasting more than three months after SARS-CoV-2 infection. The prevalence of LC, and the impact of co-infection with prevalent pathogens such as Mycobacterium tuberculosis (Mtb), in low- and middle-income countries remain unclear. We aimed to address these gaps in two Mtb-exposed populations.<br><br>METHODS: We recruited HIV-uninfected pulmonary tuberculosis (TB) patients (n=36) and their household contacts (n=63) in Peru, and healthcare workers (n=202) in Kenya. We collected clinical data using study instruments adapted from a United States based study of LC. Participants were sampled within 2 years of SARS-CoV-2 diagnosis.<br><br>RESULTS: In Peru, 41.4% participants reported LC symptoms, with no TB-associated significant differences in the prevalence or clinical phenotypes of LC. The most common LC symptoms were neurological (e.g., headache and trouble sleeping) and musculoskeletal (e.g., back pain). Kenyan participants reported acute, but no LC symptoms, and reported a decline in the quality of life during acute infection. In Peru, the post-COVID-19 period was associated with a significant decline in all quality-of-life dimensions (p<0.01), except depression and anxiety (p=0.289).<br><br>CONCLUSION: This study shows that LC prevalence was high in Peru, where TB status was not linked to LC symptoms. Those with LC reported high levels of musculoskeletal and neurological symptoms. Unexpectedly, healthcare workers in Kenya denied the presence of LC symptoms. These findings highlight the need for long-term follow-up and larger studies in different geographic settings to dissect the impact of TB comorbidity on LC.},
}
@article {pmid40342248,
year = {2025},
author = {Tawfiq, E and Chen, R and Honeyman, DA and Dawson, R and Kunasekaran, M and Notaras, A and Gurdasani, D and Skouteris, H and Ayton, D and MacIntyre, CR},
title = {Long Covid Symptom Clusters, Correlates and Predictors in a Highly Vaccinated Australian Population in 2023.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70273},
pmid = {40342248},
issn = {1369-7625},
support = {//E.T., R.C., D.A.H., R.D., M.K., A.N. and D.G. are supported by the Balvi Filantropic Fund. C.R.M. is funded by NHMRC Investigator Grant 2016907. D.A.H. and A.N. are funded through MRFF (grant ID 2017048). The funding sources had no role in the study design, data collection, analysis or interpretation, reporting or publication of this work./ ; },
mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/prevention &amp; control ; Middle Aged ; Australia/epidemiology ; Adult ; Cross-Sectional Studies ; Aged ; *COVID-19 Vaccines/administration &amp; dosage ; Risk Factors ; Young Adult ; Prevalence ; SARS-CoV-2 ; Adolescent ; Severity of Illness Index ; Vaccination/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Limited data exists regarding long Covid burden following Omicron infection in highly vaccinated populations.<br><br>OBJECTIVE: To (1) characterise long Covid prevalence and predictors and (2) identify key symptom clusters and their correlates among long Covid patients, during an Omicron-predominant period in a highly vaccinated population.<br><br>DESIGN: Anonymous, online, cross-sectional survey.<br><br>SETTING: January 2023, Australia.<br><br>PARTICIPANTS: Residents aged&#x2009;&#x2265;&#x2009;18 years with self-reported history of test-positive Covid-19. The main variables studied were socio-demographic characteristics, Covid-19 risk factors, vaccination, infection history and experiences with long Covid.<br><br>MAIN OUTCOME MEASURES: Long Covid symptoms. Symptom-based clustering was used to identify long Covid symptom clusters and their functional correlates. Predictors of long Covid occurrence and severity were assessed using multivariable logistic regression.<br><br>RESULTS: Overall, 240/1205 participants (19.9%) reported long Covid. Long Covid risk was significantly higher for women OR 1.71 (95% CI: 1.17-2.51), people with comorbidities 2.19 (95% CI: 1.56-3.08) and those using steroid inhalers for Covid-19 treatment (2.34 [95% CI: 1.29-4.24]). Long-Covid risk increased with increasing Covid-19 infection severity (moderately severe symptoms: 2.23 [95% CI: 1.50-3.30], extremely severe symptoms: 5.80 [95% CI: 3.48-9.66], presented to ED/hospitalised: 7.22 [95% CI: 3.06-17.03]). We found no significant difference in the likelihood of long Covid between the Omicron and pre-Omicron periods, vaccination status and participant age. We identified two long Covid clusters (pauci-symptomatic, n&#x2009;=&#x2009;170, vs. polysymptomatic, n&#x2009;=&#x2009;66). Polysymptomatic cluster membership was associated with worse functioning (impacts on work, moderate activity, emotions and energy). Severity acute infection was strongly predictive of polysymptomatic cluster membership (5.72 [2.04-17.58]). Monoclonal antibody treatment was strongly associated with pauci-symptomatic cluster membership (0.02 [0.00-0.13]).<br><br>DISCUSSION: Our study shows that long Covid is an important health burden in Australia, including during the Omicron era, and identifies several risk factors. We found a subgroup of patients characterised by more symptoms and worse functional outcomes. Our findings can inform policies for protecting vulnerable populations and frameworks for long Covid risk assessment and management.<br><br>CONCLUSIONS: One-in-five people may suffer long Covid after acute Covid-19 infection, with similar risk across age groups. Omicron variants appear not to have a lower risk compared to earlier variants in our study. A cumulative number of symptoms can help triage long Covid patients.<br><br>We did not involve patients or the public in the design of the questionnaire. However, after a soft launch, we revised some survey questions by reviewing early responses from patients and the public.},
}
@article {pmid40341636,
year = {2025},
author = {Ho, L and Kwong, MH and Yuen, KW and Yuen, SHS and Hung, PC and Zhang, D and Wong, SYS and Chung, VCH},
title = {Understanding intentions to use a multi-component supported self-management platform for long COVID-19: a mixed-methods evaluation in Hong Kong.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {16086},
pmid = {40341636},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/epidemiology/psychology/therapy ; Hong Kong/epidemiology ; Female ; Male ; *Self-Management/methods ; Adult ; Middle Aged ; Cross-Sectional Studies ; SARS-CoV-2/isolation &amp; purification ; Intention ; Aged ; Young Adult ; Surveys and Questionnaires ; Smartphone ; },
abstract = {A culturally appropriate, multi-component self-management platform was developed to facilitate Long COVID-19 recovery in Hong Kong, comprising a smartphone application, a website, and a customer relationship management (CRM)-based messaging system. Using a mixed-methods design, we evaluated users' intentions to utilise the platform through the behavioural attributes of the Meta-UTAUT (Meta-analysis-based modified Unified Theory of Acceptance and Use of Technology) framework. Structured interviews were conducted to explore themes influencing users' intentions to use the platform, focusing on different attributes. Themes from the interviews were summarised using directed content and thematic analyses. These results informed the design of a cross-sectional survey quantifying the influence of those attributes on users' utilisation of the platform. Multivariate logistic regressions were conducted to investigate the associations between sociodemographic and health characteristics and the likelihood of responses to each attribute. Analysis of 45 interviews identified 17 themes influencing platform use, across six attributes: performance expectancy, effort expectancy, social influence, facilitating conditions, perceived information security, and perceived enjoyment. The survey of 326 users revealed that each of these attributes influenced the intentions of over 80% of participants using the platform. Gender, age, educational attainment, and employment status were significantly associated with their responses to specific attributes. Supported self-management is an emerging intervention for Long COVID-19. While online platforms enhance access to health information, interactions through CRM-based messaging systems may optimise professional and emotional support, thereby improving user engagement. Resources may be directed towards alleviating digital barriers, particularly for older populations.},
}
@article {pmid40340717,
year = {2025},
author = {Sardell, J and Pearson, M and Chocian, K and Das, S and Taylor, K and Strivens, M and Gupta, R and Rochlin, A and Gardner, S},
title = {Reproducibility of genetic risk factors identified for long COVID using combinatorial analysis across US and UK patient cohorts with diverse ancestries.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {516},
pmid = {40340717},
issn = {1479-5876},
mesh = {Humans ; *COVID-19/genetics/epidemiology ; Reproducibility of Results ; United States/epidemiology ; Genome-Wide Association Study ; Risk Factors ; *Genetic Predisposition to Disease ; United Kingdom/epidemiology ; Cohort Studies ; SARS-CoV-2 ; Male ; Female ; Polymorphism, Single Nucleotide/genetics ; White People/genetics ; Middle Aged ; White ; },
abstract = {BACKGROUND: Long COVID is a major public health burden causing a diverse array of debilitating symptoms in tens of millions of patients globally. In spite of this overwhelming disease prevalence, staggering cost, severe impact on patients' lives and intense global research efforts, study of the disease has proved challenging due to its complexity. Genome-wide association studies (GWAS) have identified only four loci potentially associated with the disease, although these results did not statistically replicate between studies. A previous combinatorial analysis study identified a total of 73 genes that were highly associated with two long COVID cohorts in the predominantly (> 91%) white European ancestry Sano GOLD population, and we sought to reproduce these findings in the independent and ancestrally more diverse All of Us (AoU) population.<br><br>METHODS: We assessed the reproducibility of the 5343 long COVID disease signatures from the original study in the AoU population. Because the very small population sizes provide very limited power to replicate findings, we initially tested whether we observed a statistically significant enrichment of the Sano GOLD disease signatures that are also positively correlated with long COVID in the AoU cohort after controlling for population substructure.<br><br>RESULTS: For the Sano GOLD disease signatures that have a case frequency greater than 5% in AoU, we consistently observed a significant enrichment (77-83%, p&#x2009;<&#x2009;0.01) of signatures that are also positively associated with long COVID in the AoU cohort. These encompassed 92% of the genes identified in the original study. At least five of the disease signatures found in Sano GOLD were also shown to be individually significantly associated with increased long COVID prevalence in the AoU population. Rates of signature reproducibility are strongest among self-identified white patients, but we also observe significant enrichment of reproducing disease associations in self-identified black/African-American and Hispanic/Latino cohorts. Signatures associated with 11 out of the 13 drug repurposing candidates identified in the original Sano GOLD study were reproduced in this study.<br><br>CONCLUSION: These results demonstrate the reproducibility of long COVID disease signal found by combinatorial analysis, broadly validating the results of the original analysis. They provide compelling evidence for a much broader array of genetic associations with long COVID than previously identified through traditional GWAS studies. This strongly supports the hypothesis that genetic factors play a critical role in determining an individual's susceptibility to long COVID following recovery from acute SARS-CoV-2 infection. It also lends weight to the drug repurposing candidates identified in the original analysis. Together these results may help to stimulate much needed new precision medicine approaches to more effectively diagnose and treat the disease. This is also the first reproduction of long COVID genetic associations across multiple populations with substantially different ancestry distributions. Given the high reproducibility rate across diverse populations, these findings may have broader clinical application and promote better health equity. We hope that this will provide confidence to explore some of these mechanisms and drug targets and help advance research into novel ways to diagnose the disease and accelerate the discovery and selection of better therapeutic options, both in the form of newly discovered drugs and/or the immediate prioritization of coordinated investigations into the efficacy of repurposed drug candidates.},
}
@article {pmid40337174,
year = {2025},
author = {Stussman, B and Camarillo, N and McCrossin, G and Stockman, M and Norato, G and Vetter, CS and Ferrufino, A and Adedamola, A and Grayson, N and Nath, A and Chan, L and Walitt, B and Chin, LMK},
title = {Post-exertional malaise in Long COVID: subjective reporting versus objective assessment.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1534352},
pmid = {40337174},
issn = {1664-2295},
abstract = {BACKGROUND: Post-exertional malaise (PEM) is a central feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and has emerged as a prominent feature of Long COVID. The optimal clinical approach to PEM is inconclusive, and studies of the impact of exercise have yielded contradictory results.<br><br>OBJECTIVE: The objective of this study was to examine PEM in Long COVID by assessing the prevalence of self-reported PEM across study cohorts and symptom responses of Long COVID patients to a standardized exercise stressor. Secondarily, Long COVID symptom responses to exercise were compared to those of ME/CFS and healthy volunteers.<br><br>METHODS: Data from three registered clinical trials comprised four cohorts in this study: Long COVID Questionnaire Cohort (QC; n&#x202f;=&#x202f;244), Long COVID Exercise Cohort (EC; n&#x202f;=&#x202f;34), ME/CFS cohort (n&#x202f;=&#x202f;9), and healthy volunteers (HV; n&#x202f;=&#x202f;9). All cohorts completed questionnaires related to physical function, fatigue, and/or PEM symptoms. EC also performed a standardized exercise test (cardiopulmonary exercise test, CPET), and the PEM response to CPET was assessed using visual analog scales and qualitative interviews (QIs) administered serially over 72&#x202f;h. EC PEM measures were compared to ME/CFS and HV cohorts. A secondary analysis of QI explored positive responses to CPET among EC, ME/CFS and HV.<br><br>RESULTS: Self-reported PEM was 67% in QC and estimated at 27% in EC. Only 2 of 34 EC patients (5.9%) were observed to develop PEM after a CPET. In addition, PEM responses after CPET in Long COVID were not as severe and prolonged as those assessed in ME/CFS. Twenty-two of 34 EC patients (64.7%) expressed at least one of 7 positive themes after the CPET.<br><br>CONCLUSION: Self-report of PEM is common in Long COVID. However, observable PEM following an exercise stressor was not frequent in this small cohort. When present, PEM descriptions during QI were less severe in Long COVID than in ME/CFS. Positive responses after an exercise stressor were common in Long COVID. Exercise testing to determine the presence of PEM may have utility for guiding clinical management of Long COVID.},
}
@article {pmid40337099,
year = {2025},
author = {Mohr, I and Brand, M and Weber, C and Langel, A and Langel, J and Michl, P and Leidner, VY and Olkus, A and Köhrer, S and Merle, U},
title = {Mental and Physical Health in Wilson Disease Patients With SARS-CoV-2 Infection and Relevance of Long-COVID.},
journal = {JIMD reports},
volume = {66},
number = {3},
pages = {e70021},
pmid = {40337099},
issn = {2192-8304},
abstract = {SARS-CoV-2 infection and Long COVID (LC) might lead to a significant deterioration of physical and mental health. Wilson disease (WD) patients have a chronic liver and/or neuropsychiatric disease, making it particularly interesting to investigate LC in WD. 51 WD patients were retrospectively examined, evaluating physical and mental health by a survey and neuropsychological tests (SF-12, PSQI, ISI, Epworth, Chalder-fatigue scale, PHQ-9, GAD-7, PSS, FLei) before and ~11 months after SARS-CoV-2 infection. LC was defined as the development of new, at least moderately severe symptoms (shortness of breath, chest pain, fatigue, brain fog, exercise capacity, concentration disturbances) and/or worsening of pre-existing symptoms. 70.6% had predominant hepatic and 29.4% had neuropsychiatric symptoms at WD diagnosis. Median age was 39 years; 56.1% were female. Patients were in stable maintenance phase with a median treatment duration of 23 years. When compared to before COVID-19, WD patients had significantly worse physical life quality, sleeping quality, and fatigue. After COVID-19, a high percentage of WD patients reported concentration disorders (60%), fatigue (55%), reduced exercise capacity (50%), shortness of breath (40%), chest pain (20%) and feeling of brain fog (15%). 39.2% (n = 20) of the WD patients were classified as LC. This LC-WD subgroup showed significantly impaired quality of life, a high stress level, and sleeping disturbances, fatigue, depression, anxiety, and cognitive impairment. A large proportion of WD patients experience LC symptoms, reduced life quality, and sleeping disorders after SARS-CoV-2 infection. WD patients post-infection should be well monitored and supported if they develop persisting symptoms or neuro-psychological problems.},
}
@article {pmid40336577,
year = {2025},
author = {Li, K and Wei, Y and Hung, CT and Wong, CKH and Xiong, X and Chan, PKS and Zhao, S and Guo, Z and Lin, G and Chi, Q and Kwan Yam, CH and Chow, TY and Li, C and Jiang, X and Leung, SY and Kwok, KL and Yeoh, EK and Chong, KC},
title = {Post-pandemic excess mortality of COVID-19 in Hong Kong: a retrospective study.},
journal = {The Lancet regional health. Western Pacific},
volume = {58},
number = {},
pages = {101554},
pmid = {40336577},
issn = {2666-6065},
abstract = {BACKGROUND: As the COVID-19 pandemic shifted into the post-pandemic period in early 2023, following the COVID-19 normalization with relaxation of stringent control measures and high vaccination coverage in Hong Kong, its long-term impact on mortality remains challenging with necessary needs of data-driven insights. This study examined the pattern of post-pandemic excess mortality in Hong Kong.<br><br>METHODS: We analyzed weekly inpatient death data from public hospitals from January 1, 2013, to June 1, 2024, using a mixed model with over-dispersed Poisson regression. Expected mortality was estimated as the difference between observed mortality and baseline derived from pre-pandemic data. Age-stratified analyses of overall and cause-specific mortality were conducted across the pre-Omicron pandemic, Omicron, and post-pandemic periods.<br><br>FINDINGS: In the post-pandemic period, the excess mortality declined but remained six-fold higher (37.66 [95% CI: 32.72-42.60] per 100,000) than pre-Omicron level, maintaining significance after adjusting for age (32.79 [95% CI: 28.13-37.46] per 100,000). The older population experienced sustained excess mortality, with crude estimates of 100.51 and 586.74 per 100,000 among those aged 65-79 years and &#x2265;80 years, respectively, primarily due to respiratory diseases. Younger population showed near-zero overall excess mortality, whereas increased excess mortality among them occurred in heart disease, cerebrovascular disease, and injuries.<br><br>INTERPRETATION: Our findings highlight the lasting mortality impact of pandemic among vulnerable populations, specifically the older population, possibly due to the post-COVID conditions and circulating COVID-19, suggesting the need for targeted interventions for this group.<br><br>FUNDING: Health and Medical Research Fund.},
}
@article {pmid40335886,
year = {2025},
author = {Naik, H and Zhu, B and Er, L and Sbihi, H and Janjua, NZ and Smith, PM and Tran, KC and Levin, A and Zhang, W},
title = {Work Productivity Loss in People Living With Long COVID Symptoms Over 2 Years From Infection.},
journal = {Journal of occupational and environmental medicine},
volume = {67},
number = {8},
pages = {588-594},
pmid = {40335886},
issn = {1536-5948},
mesh = {Humans ; *COVID-19/epidemiology/complications/economics ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Efficiency ; British Columbia/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; Aged ; Survivors/statistics &amp; numerical data ; },
abstract = {OBJECTIVE: To evaluate the work productivity loss in people experiencing long COVID symptoms more than 2 years after infection.<br><br>METHODS: In a cross-sectional study, employed adults from British Columbia, Canada, who had a polymerase chain reaction-confirmed SARS-CoV-2 infection more than 2 years earlier, completed an online survey incorporating the Valuation of Lost Productivity questionnaire. Long COVID status was self-reported. The data were weighted to mirror the demographic and clinical profile of COVID-19 survivors in British Columbia.<br><br>RESULTS: Of 906 participants, 165 (18.7%) reported long COVID symptoms. These individuals reported greater total productivity loss than other COVID-19 survivors (adjusted mean difference, 99.2 hours per 3 months; 95% confidence interval, 44.9-167.5).<br><br>CONCLUSIONS: Long COVID is associated with substantial work productivity loss. Given the large number of individuals affected by long COVID, this has significant implications for healthcare systems, the workforce, and economies.},
}
@article {pmid40335840,
year = {2025},
author = {Bae, G and Yang, Z and Bucci, D and Wegner, C and Schäfer, H and Singh, Y and Lonati, C and Trautwein, C},
title = {Longitudinal lipoprotein and inflammatory mediators analysis uncover persisting inflammation and hyperlipidemia following SARS-CoV-2 infection in long COVID-19.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {21},
number = {3},
pages = {65},
pmid = {40335840},
issn = {1573-3890},
mesh = {Humans ; *COVID-19/complications/blood ; *Lipoproteins/blood ; Male ; *Inflammation/blood/metabolism ; Female ; Middle Aged ; *Hyperlipidemias/blood/etiology ; Cytokines/blood ; *Inflammation Mediators/blood ; Adult ; SARS-CoV-2 ; Magnetic Resonance Spectroscopy ; Aged ; Longitudinal Studies ; },
abstract = {INTRODUCTION: Individuals suffering from acute COVID-19 (AC) often develop long COVID-19 (LC) syndrome that is associated with aberrant levels of lipoproteins and inflammatory mediators. Yet, these dysregulations are heterogenous due to the uncertain prevalence and require a more extensive characterization.<br><br>OBJECTIVES: This study aimed to investigate LC-associated dysregulations in inflammatory mediators and lipids by longitudinal Nuclear Magnetic Resonance (NMR) lipoprotein analysis and cytokine profiling in human blood.<br><br>METHODS: We quantitatively profiled lipoproteins and inflammatory parameters in LC patients at 5 (n&#xa0;=&#xa0;95), 9&#xa0;(n&#xa0;=&#xa0;73), 12&#xa0;(n&#xa0;=&#xa0;95), 16&#xa0;(n&#xa0;=&#xa0;78), and 20&#xa0;(n&#xa0;=&#xa0;85) months post AC by in vitro diagnostics research (IVDr)-based NMR spectroscopy. Simultaneously, we assessed inflammatory meditators with a 13-plex cytokine panel by flow cytometry. We then compared the lipoprotein profiles with historical data from AC (N&#x2009;=&#x2009;307) and healthy cohorts collected before the COVID-19 pandemic (N&#x2009;=&#x2009;305), whereas the cytokine profiles were correlated with that of the AC cohort.<br><br>RESULTS: We identified 31 main and 80 significantly altered subclass lipoproteins, respectively. LC was associated with higher serum levels of very low-density, intermediate-density, low-density, high-density lipoproteins, along with triglycerides, cholesterols, and apolipoprotein a-I &amp; a-II lipoproteins compared to the healthy cohort. We also observed significantly lower concentrations of NMR-based inflammatory parameters in LC than in AC cohort, whilst proinflammatory mediators IFN-&#x3b1;2, IFN-&#x3b3;, TNF-&#x3b1;, CXCL8/IL-8, IL-12p70, IL-17&#xa0;A, and IL-23 displayed significantly higher concentrations in LC compared with the AC cohort. Conversely, CCL2/MCP-1, IL-6, and IL-18 were significantly higher in the AC cohort than in LC.<br><br>CONCLUSION: Our findings demonstrate a persistent hyperlipidemic phenotype in LC alongside signs of chronic inflammation and lipoprotein metabolism that vary in states of acute and chronic inflammation.},
}
@article {pmid40335476,
year = {2025},
author = {O'Mahoney, LL and Routen, A and Gillies, C and Jenkins, SA and Almaqhawi, A and Ayoubkhani, D and Banerjee, A and Brightling, C and Calvert, M and Cassambai, S and Ekezie, W and Funnell, MP and Welford, A and Peace, A and Evans, RA and Jeffers, S and Kingsnorth, AP and Pareek, M and Seidu, S and Wilkinson, TJ and Willis, A and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Ward, T and Khunti, K},
title = {The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4249},
pmid = {40335476},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/epidemiology/complications/physiopathology/virology ; *Post-Acute COVID-19 Syndrome/epidemiology/physiopathology/virology ; Risk Factors ; SARS-CoV-2/pathogenicity ; },
abstract = {The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.},
}
@article {pmid40334046,
year = {2025},
author = {Takaoka, S and Saito, H and Kawate, M and Tanaka, C and Wu, Y and Kosugi, S and Yamada, T and Tabuchi, T and Wakaizumi, K},
title = {Exploring the presence of long COVID-like symptoms in patients with chronic pain: a large-scale internet-based cross-sectional study in Japan.},
journal = {Pain},
volume = {166},
number = {10},
pages = {2412-2420},
doi = {10.1097/j.pain.0000000000003643},
pmid = {40334046},
issn = {1872-6623},
support = {21H04856//Japan Society for the Promotion of Science/ ; 20K10467//Japan Society for the Promotion of Science/ ; 20K19633//Japan Society for the Promotion of Science/ ; 20K1372//Japan Society for the Promotion of Science/ ; 24K00498//Japan Society for the Promotion of Science/ ; 24K02541//Japan Society for the Promotion of Science/ ; JPMJPF2017//Japan Science and Technology Agency/ ; 21HA2016//Health and Labour Sciences Research Grant/ ; SK202116//2021-2022 Strategic Research Promotion, Yokohama City University/ ; Using Health Metrics to Monitor and Evaluate the Impact of Health Policies//Tokyo Foundation for Policy Research/ ; },
mesh = {Humans ; Japan/epidemiology ; *Chronic Pain/epidemiology ; *COVID-19/epidemiology/complications ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; Aged ; Internet ; Fatigue/epidemiology ; Surveys and Questionnaires ; Sleep Wake Disorders/epidemiology ; SARS-CoV-2 ; },
abstract = {Individuals with chronic pain not only endure the direct burden of pain but also experience various symptoms, including sleep disturbances and fatigue, which deteriorate their quality of life. Notably, these symptoms closely resemble those observed in "long COVID," a prolonged health complication that can arise after coronavirus disease 2019 (COVID-19) infection. Because the similarities between chronic pain and long COVID remain unexplored, this study aimed to investigate their relationship using Japanese epidemiological data. Using the Japan COVID-19 and Society Internet Survey in 2022, which included 32,000 participants, we analyzed data on the presence of chronic pain, history of COVID-19 infection, and presence of 17 long COVID-like symptoms, including gastrointestinal upset, back pain, limb/joint pain, headache, chest pain, shortness of breath, dizziness, sleep disorder, hearing disorder, taste disorder, smell disorder, memory impairment, poor concentration, hair loss, decreased libido, fatigue, and cough. Individuals with history of COVID-19 experienced a significantly greater number of long COVID-like symptoms (median: 5) compared with those with neither COVID-19 nor chronic pain (median: 4, P < 0.001). Individuals with chronic pain alone and those with both COVID-19 and chronic pain exhibited an even greater number of symptoms (median: 8 and 9, respectively). In addition, individuals with chronic pain exhibited greater prevalence odds for 15 of the 17 symptoms than those with neither COVID-19 nor chronic pain (P < 0.001). Our findings indicate that long COVID-like symptoms are not specifically associated with COVID-19. Instead, the data suggest that chronic pain contributes as an independent risk factor for these symptoms.},
}
@article {pmid40333937,
year = {2025},
author = {Abbas, U and Hussain, N and Tanveer, M and Laghari, RN and Ahmed, I and Rajper, AB},
title = {Frequency and predictors of depression and anxiety in chronic illnesses: A multi disease study across non-communicable and communicable diseases.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0323126},
pmid = {40333937},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; Chronic Disease/psychology/epidemiology ; Middle Aged ; *Anxiety/epidemiology/etiology ; *Depression/epidemiology/etiology ; *Communicable Diseases/psychology/epidemiology ; Adult ; *Noncommunicable Diseases/psychology/epidemiology ; Case-Control Studies ; Aged ; COVID-19 ; Comorbidity ; },
abstract = {BACKGROUND: Depression and anxiety are among the most common mental health conditions globally that impact the lifestyle of affected individuals. Mental conditions and chronic diseases are linked to each other bidirectionally. Depression and anxiety with comorbid chronic conditions are often neglected or under-screened and possess challenges in treatment. This study aimed to know the frequency and determinants of depression and anxiety along with the severity level among common chronic communicable and non-communicable diseases.<br><br>METHODS: We enrolled 200 healthy controls and 800 cases with equal number (n&#x2009;=&#x2009;400) of patients with communicable and non-communicable diseases. Depression and anxiety were screened through Hamilton's rating scale for depression and anxiety separately. We also measured the determinants of severe depression among patients with chronic diseases. Data was analyzed through SPSS version 23.<br><br>RESULTS: We found higher frequency of depression (31% vs 11%; p=<0.001) and anxiety (13.25% vs 6%; p&#x2009;=&#x2009;0.021) among cases as compared to healthy controls respectively. We found higher levels of depression among participants with non-communicable diseases as compared to communicable diseases (37.25% vs 24.75%; p&#x2009;<&#x2009;0.05) respectively. Moreover, there was a higher frequency of anxiety in participants with communicable diseases as compared to those with non-communicable diseases, but the difference was non-significant (14% vs 12.5% p&#x2009;=&#x2009;0.081). Among non-communicable diseases the highest percentage was found among individuals with cancer (67%), followed by diabetes (38%), cardiovascular diseases (33%) and respiratory disorders (11%). Among participants with communicable diseases, the highest percentage of depression was found in patients with Tuberculosis (29%) followed by HIV/AIDS (28%), Long COVID-19 (25%) and Hepatitis B/C (17%).<br><br>CONCLUSION: There is a significantly higher percentage of depression and anxiety among participants with chronic diseases. It calls for a comprehensive approach to patient care that incorporates mental health as a fundamental aspect of the treatment and management of chronic diseases. Understanding the predictors of severe depression across different chronic conditions helps in stratifying patients who may benefit most from integrated psychiatric and psychological interventions.},
}
@article {pmid40330487,
year = {2025},
author = {Rodriguez-Perez, AI and Serrano-Heras, G and Labandeira, CM and Camacho-Meño, L and Castro-Robles, B and Suarez-Quintanilla, JA and Muñoz-López, M and Piqueras-Landete, P and Guerra, MJ and Segura, T and Labandeira-Garcia, JL},
title = {Serum angiotensin type-1 receptor autoantibodies and neurofilament light chain as markers of neuroaxonal damage in post-COVID patients.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1571027},
pmid = {40330487},
issn = {1664-3224},
mesh = {Humans ; *Receptor, Angiotensin, Type 1/immunology ; *Autoantibodies/blood/cerebrospinal fluid/immunology ; *COVID-19/immunology/blood/complications ; Male ; Female ; Middle Aged ; Biomarkers/blood/cerebrospinal fluid ; *Neurofilament Proteins/blood/immunology ; *SARS-CoV-2/immunology ; Renin-Angiotensin System/immunology ; Aged ; Adult ; },
abstract = {INTRODUCTION: Dysregulation of autoimmune responses and the presence of autoantibodies (AA), particularly those related to the renin-angiotensin system (RAS), have been implicated in the acute phase of COVID-19, and persistent dysregulation of brain RAS by RAS-related autoantibodies may also contribute to neurological symptoms of post-COVID.<br><br>METHODS: We analyzed levels of serum and CSF RAS AA in post-COVID patients with neurological symptoms, individuals who have fully recovered from COVID-19 (after-COVID controls), and uninfected individuals, and their possible correlations with the serum marker of neuroaxonal damage neurofilament light chain (NfL) and the degrees of cognitive deficit.<br><br>RESULTS: Both in serum and CSF, levels of AA agonists of the pro-inflammatory angiotensin II type 1 receptors (AT1-AA) were significantly elevated in this cohort of neurological post-COVID patients compared to both uninfected and after-COVID controls and correlated with serum levels of NfL. Changes in serum and CSF levels of AA promoting the RAS anti-inflammatory axis (upregulation of AA agonists of AT2 and Mas receptors, downregulation of AA antagonists of ACE2) suggest upregulation of the RAS compensatory response in this cohort of neurological post-COVID patients. Post-COVID patients with more pronounced cognitive impairment exhibited significantly higher CSF levels of MasR-AA and a trend toward elevated AT2-AA. Persistent brain RAS dysregulation, particularly persistent increase in AT1-AA, and its correlation with neuroaxonal damage markers and cognitive impairment, may play a significant role in neurological symptoms associated with post-COVID. Serum levels of NfL and AT1-AA may be interesting biomarkers for the early identification of CNS involvement in patients with neurological symptoms and a history of COVID-19. However, post-COVID is a highly heterogeneous entity and may result from various underlying mechanisms. The present study includes a cohort, which may differ from other cohorts with different clinical profiles, which may show different results on NfLs and CSF RAS autoantibodies, particularly AT1-AA.<br><br>CONCLUSION: These findings highlight the potential of targeting AT1 receptors as a therapeutic strategy for mitigating cognitive deficits in post-COVID patients showing upregulated AT1-AA levels.},
}
@article {pmid40330357,
year = {2025},
author = {Chandrasekhar, T and Ravishankar, C and Geethanjali, A and Lahari, T},
title = {Outcomes in Patients with Long COVID-19 One Year After their Discharge from Intensive Care Units.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e81739},
pmid = {40330357},
issn = {2168-8184},
abstract = {Introduction Survivors of prolonged severe COVID-19 who are treated at ICUs are at risk for physical and psychological complications, including lung injury and multi-organ dysfunction. As the number of survivors of severe COVID-19 increases, it is necessary to understand the trajectory of the disease and the patient care needed after discharge from the ICU. This study tries to efficiently assess the long-term clinical sequelae among patients with prolonged severe COVID-19 who were admitted to the ICU, one year after their discharge. The parameters tested included the chronic obstructive pulmonary disease assessment test (CAT) score, pulmonary function tests, and laboratory data. Materials and methods The study population included 454 patients who were followed up one year after surviving ICU admission for severe COVID-19. All the patients who presented with signs and symptoms to the hospital were examined further. They underwent the necessary investigations, assessments, and systemic examinations. The results of all the laboratory and radiological investigations were reviewed. During the SARS-CoV-2 pandemic, all the patient details were entered into a hospital information management system from which the data was retrieved. Mean with standard deviation (SD) or median or interquartile ranges (IQR) were used to assess the continuous variables, whereas numbers and percentages were used for categorical variables. Statistical significance was calculated by the Chi-square test. Results The median age of the study population was 64 (IQR 57-74) years and 64.7% (294/454) were male patients. The median follow-up time was 367 days. During the follow-up period, 14.9% (68/454) of the patients were readmitted to the ICU. The mean length of hospital stay was 12 days (IQR 8-20 days). Among the readmitted patients (n=68), 17.6% (12/68) were on mechanical ventilation and the remaining 82.3% (56/68) received oxygen therapy. One patient underwent extracorporeal membrane oxygenation. The hospital mortality rate observed among these ICU survivors was 10.2%. The Health-Related Quality of Life (HRQOL) score at baseline i.e. before the ICU admission (52.5 (SD, 9.2); p<0.001) was better than that observed at the one-year follow-up (44.3 (SD, 9.5); p<0.001). Moreover, the clinical frailty scale and cognitive symptoms were significantly different at the follow up assessment versus the baseline (p<0.001). The proportion of patients with a grade of 0-2 on the Modified Medical Research Council (mMRC) dyspnea scale was almost similar at baseline and the one-year follow-up, whereas a breathlessness grade of 3-4 on the scale was observed in 39.8% of the study population. Conclusion The management of ICU survivors after severe COVID requires a multi-disciplinary approach. It includes preventive measures and rehabilitation services along with appropriate treatment strategies to relieve the residual symptoms.},
}
@article {pmid40330302,
year = {2025},
author = {He, C and Xie, J and Fang, W and Guo, B and Shi, Y and Li, A and Liu, H and Zhu, Z and Bao, W and Niu, X and Wang, S and Fu, J and Li, H and Xie, W},
title = {Dynamic brain glymphatic changes and cognitive function in COVID-19 recovered patients: a DTI-ALPS prospective cohort study.},
journal = {Frontiers in psychology},
volume = {16},
number = {},
pages = {1465660},
pmid = {40330302},
issn = {1664-1078},
abstract = {OBJECTIVE: This study aimed to evaluate brain glymphatic function in COVID-19 recovered patients using the non-invasive Diffusion Tensor Imaging-Analysis Along the Perivascular Space (DTI-ALPS) technique. The DTI-ALPS technique was employed to investigate changes in brain glymphatic function in these patients and explore correlations with cognitive function and fatigue.<br><br>MATERIALS AND METHODS: Follow-up assessments were conducted at 1, 3, and 12&#x202f;months post-recovery. A total of 31 patients completed follow-ups at all three time points, with 30 healthy controls (HCs) for comparison.<br><br>RESULTS: Compared to HCs, COVID-19 recovered patients showed a significant decline in MoCA scores at 3&#x202f;months post-recovery (p&#x202f;<&#x202f;0.05), which returned to near-normal levels by 12&#x202f;months. Mental fatigue, measured by the Fatigue Assessment Scale (FAS), was significantly higher in COVID-19 patients at all follow-up points compared to HCs (p&#x202f;<&#x202f;0.05). The DTI-ALPS index in both hemispheres showed significant differences at 3&#x202f;months post-recovery compared to HCs (p&#x202f;<&#x202f;0.001), indicating increased glymphatic activity. Longitudinal analysis revealed a peak in the DTI-ALPS index at 3&#x202f;months post-recovery, which then decreased by 12&#x202f;months. Correlation analysis showed a significant negative correlation between the Bilateral brain hemisphere DTI-ALPS index and MoCA scores (right side: r&#x202f;=&#x202f;-0.373, p&#x202f;=&#x202f;0.003; left side: r&#x202f;=&#x202f;-0.255, p&#x202f;=&#x202f;0.047), and a positive correlation with mental fatigue (right side: r&#x202f;=&#x202f;0.275, p&#x202f;=&#x202f;0.032; left side: r&#x202f;=&#x202f;0.317, p&#x202f;=&#x202f;0.013).<br><br>CONCLUSION: This study demonstrates dynamic changes in brain glymphatic function in COVID-19 recovered patients, with a peak in activity at 3&#x202f;months post-recovery. These changes are associated with cognitive function and mental fatigue, suggesting potential targets for addressing neurological symptoms of long COVID. The non-invasive DTI-ALPS technique proves to be a valuable tool for assessing brain glymphatic function in this population.},
}
@article {pmid40330025,
year = {2025},
author = {Smail, SW and Albarzinji, N and Salih, RH and Taha, KO and Hirmiz, SM and Ismael, HM and Noori, MF and Azeez, SS and Janson, C},
title = {Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1537456},
pmid = {40330025},
issn = {2235-2988},
mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *COVID-19/microbiology/physiopathology/therapy/complications ; *SARS-CoV-2 ; *Gastrointestinal Microbiome ; },
abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.},
}
@article {pmid40329907,
year = {2025},
author = {Hadidchi, R and Al-Ani, Y and Piskun, H and Pakan, R and Duong, KS and Jamil, H and Wang, SH and Henry, S and Maurer, CW and Duong, TQ},
title = {Impact of COVID-19 on long-term outcomes in Parkinson's disease.},
journal = {European journal of neurology},
volume = {32},
number = {5},
pages = {e70013},
pmid = {40329907},
issn = {1468-1331},
mesh = {Humans ; *Parkinson Disease/epidemiology/complications/drug therapy/mortality ; *COVID-19/epidemiology/complications/mortality ; Male ; Female ; Aged ; Retrospective Studies ; Middle Aged ; Comorbidity ; Aged, 80 and over ; },
abstract = {OBJECTIVES: Patients with pre-existing Parkinson's disease (PD) face higher risks of severe acute COVID-19 outcomes than matched controls, but long-term post-COVID-19 outcomes remain largely unknown. This study investigated clinical outcomes up to 3.5 years post-infection in a Bronx inner-city PD population.<br><br>METHODS: This retrospective study evaluated 3512 patients with PD in the Montefiore Health System (January 2016-July 2023), which serves a large diverse population and was an epicenter of the early COVID-19 pandemic and subsequent infection surges. Comparisons were made with PD patients without a positive SARS-CoV-2 test (defined by polymerase chain reaction test). Outcomes were post-index date all-cause mortality, major adverse cardiovascular events (MACE), altered mental status, fatigue, dyspnea, headache, psychosis, dementia, depression, anxiety, dysphagia, falls, and orthostatic hypotension. Changes in Levodopa prescriptions were also tabulated. Adjusted hazard ratios (aHR) were computed accounting for competing risks.<br><br>RESULTS: PD patients with COVID-19 had similar demographics but a higher prevalence of pre-existing comorbidities compared to PD patients without COVID-19. PD patients with COVID-19 had greater risk of mortality (aHR&#x2009;=&#x2009;1.58 [95% CI: 1.03, 2.41]), MACE (aHR&#x2009;=&#x2009;1.57 [1.19, 2.07]), dyspnea, fatigue, and fall compared to PD patients without COVID-19. Levodopa dose adjustment was higher post-infection in the COVID-19 cohort.<br><br>CONCLUSIONS: Among PD patients, COVID-19 was associated with a higher risk of adverse long-term outcomes. PD patients who survive COVID-19 may benefit from heightened clinical awareness and close follow-up. Findings highlight the need to improve post-COVID care for PD patients to mitigate disease progression and maintain quality of life.},
}
@article {pmid40329717,
year = {2025},
author = {Parwani, S and Upreti, S and Mishra, CK and Tripathi, A and Chakraborty, S and Tiwari, S},
title = {Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2.},
journal = {Current HIV research},
volume = {23},
number = {3},
pages = {145-160},
doi = {10.2174/011570162X338375250414114957},
pmid = {40329717},
issn = {1873-4251},
mesh = {Humans ; COVID-19/immunology ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use/adverse effects ; *COVID-19 Drug Treatment ; COVID-19 Vaccines/immunology ; *HIV Infections/complications/immunology/drug therapy ; Drug Repositioning ; },
abstract = {Coronavirus Disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China. Designated as an epidemic by the World Health Organization (WHO) on January 30, 2020, the virus quickly escalated to a global emergency, officially declared a pandemic in March 2020. With over 6 million recorded deaths and more than 200 identified symptoms in diverse individuals, the impact of COVID-19 is substantial. COVID-19 poses a greater risk to individuals with advanced HIV, while those with well-managed HIV are not at increased risk. Although COVID-19 vaccines are generally effective for people with HIV, some may experience reduced vaccine effectiveness and breakthrough infections due to suboptimal immune responses. Long COVID, affecting at least 65 million individuals, adds a layer of complexity. The virus's rapid mutation has led to diverse symptomatology, prompting adjustments in treatment guidelines. This review comprehensively examines repurposed antiviral drug candidates against COVID-19, explores immune responses across different age groups, delves into the mechanisms of COVID-19 vaccines, and discusses potential immunosuppressants. Additionally, the focus extends to Intravenous Immunoglobulin (IVIG), steroids, and anti-cytokine therapy as promising avenues to address cytokine release syndrome (CRS), a critical condition in COVID-19 patients.},
}
@article {pmid40328884,
year = {2025},
author = {Ruß, AK and Schreiber, S and Lieb, W and Vehreschild, JJ and Heuschmann, PU and Illig, T and Appel, KS and Vehreschild, MJGT and Krefting, D and Reinke, L and Viebke, A and Poick, S and Störk, S and Reese, JP and Zoller, T and Krist, L and Ellinghaus, D and Foesel, BU and Gieger, C and Lorenz-Depiereux, B and Witzenrath, M and Anton, G and Krawczak, M and Heyckendorf, J and Bahmer, T},
title = {Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {15791},
pmid = {40328884},
issn = {2045-2322},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; Cohort Studies ; *COVID-19/genetics/complications/epidemiology ; Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Germany/epidemiology ; Polymorphism, Single Nucleotide ; *Post-Acute COVID-19 Syndrome/epidemiology/genetics ; Prospective Studies ; },
abstract = {If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany. Each PCS score originally represented the weighted sum of the binary indicators of all, or a subset, of 12 PCS symptom complexes, assessed six months or later after the PCR test-confirmed SARS-CoV-2 infection of a participant. For various methodical reasons, however, the PCS scores were dichotomized along their respective median values in the present study, prior to the GWAS. Of the 6,383,167 single nucleotide polymorphisms included, various variants were found to be associated with at least one of the PCS scores, although not at the stringent genome-wide statistical significance level of 5 × 10[- 8]. With p = 6.6 × 10[- 8], however, the genotype-phenotype association of SNP rs9792535 at position chr9:127,166,653 narrowly missed this threshold. The SNP is located in a region including the NEK6, PSMB7 and ADGRD2 genes which, however, does not immediately suggest an etiological connection to PCS. As regards functional plausibility, variants of a possible effect mapped to the olfactory receptor gene region (lead SNP rs10893121 at position chr11:123,854,744; p = 2.5 × 10[- 6]). Impairment of smell and taste is a pathognomonic feature of both, acute COVID-19 and PCS, and our results suggest that this connection may have a genetic basis. Three other genotype-phenotype associations pointed towards a possible etiological role in PCS of cellular virus repression (CHD6 gene region), activation of macrophages (SLC7A2) and the release of virus particles from infected cells (ARHGAP44). All other gene regions highlighted by our GWAS did not relate to pathophysiological processes currently discussed for PCS. Therefore, and because the genotype-phenotype associations observed in our GWAS were generally not very strong, the complexity of the genetic background of PCS appears to be as high as that of most other multifactorial traits in humans.},
}
@article {pmid40328113,
year = {2025},
author = {Hadidchi, R and Al-Ani, Y and Choi, S and Renteria, S and Duong, KS and Henry, S and Wang, SH and Duong, TQ},
title = {Long-term outcomes of patients with a pre-existing neurological condition after SARS-CoV-2 infection.},
journal = {Journal of the neurological sciences},
volume = {473},
number = {},
pages = {123477},
doi = {10.1016/j.jns.2025.123477},
pmid = {40328113},
issn = {1878-5883},
mesh = {Humans ; *COVID-19/complications/mortality/epidemiology ; Male ; Female ; Retrospective Studies ; Aged ; Middle Aged ; *Nervous System Diseases/epidemiology/complications ; Hospitalization ; Aged, 80 and over ; },
abstract = {OBJECTIVES: This study investigated post COVID-19 outcomes of patients with pre-existing neurological conditions up to 3.5 years post-infection.<br><br>METHODS: This retrospective study consisted of 1664 patients with COVID-19 (of which 1320 had been hospitalized for acute COVID-19) and 8985 non-COVID patients from the Montefiore Health System in the Bronx (Jan-2016 to Jul-2023). Pre-existing neurological conditions include dementia, mild cognitive impairment, multiple sclerosis, and Parkinson's disease. Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) post-COVID-19. Secondary outcomes were depression, anxiety, fatigue, headache, sleep disturbances, altered mental status, and dyspnea post-COVID-19. Multivariate Cox proportional hazards model was used to calculate adjusted hazard ratios for primary outcomes. Cumulative incidence function and Fine-Gray sub-distribution hazards model analysis were performed for secondary outcomes.<br><br>RESULTS: Patients with a pre-existing neurological disorders hospitalized for COVID-19 were more likely to die (adjusted hazard ratio&#xa0;=&#xa0;1.90 [CI:1.57, 2.28], P&#xa0;<&#xa0;0.005) whereas patients non-hospitalized for COVID-19 had similar mortality rate (aHR&#xa0;=&#xa0;0.85 [CI:0.47, 1.54]. P&#xa0;=&#xa0;0.59) compared to non-COVID patients. Patients with a neurological disorders (hospitalized for COVID-19 aHR&#xa0;=&#xa0;1.76 [CI:1.53, 2.03], P&#xa0;<&#xa0;0.005; not hospitalized for COVID-19: aHR&#xa0;=&#xa0;1.50 [CI:1.09, 2.05], P&#xa0;=&#xa0;0.01) were more likely to experience a MACE compared to non-COVID-19 patients. Blacks (aHR&#xa0;=&#xa0;1.49) and Hispanics (aHR&#xa0;=&#xa0;1.35) had a higher risk of post-COVID-19 MACE. Both hospitalized and non-hospitalized COVID-19 patients were more likely to develop altered mental status, fatigue, sleep disturbance, dyspnea compared to non-COVID patients (p&#xa0;<&#xa0;0.05).<br><br>CONCLUSIONS: Patients with pre-existing neurological conditions who contracted SARS-CoV-2 were more likely to have worse outcomes compared to controls after adjusting for major competing risks. Identifying at-risk individuals could enable more diligent follow-up.},
}
@article {pmid40327758,
year = {2025},
author = {Henning, E and Musci, R and Johnson, SB and Villatoro, C and Malone, LA},
title = {Pediatric long COVID: relationships with premorbid history of anxiety or depression and health-related quality of life.},
journal = {Journal of pediatric psychology},
volume = {50},
number = {10},
pages = {919-926},
pmid = {40327758},
issn = {1465-735X},
support = {U18 HS029920/HS/AHRQ HHS/United States ; 1U18HS029920//Agency for Healthcare Research &amp; Quality/ ; 1U18HS029920//Healthcare Research &amp; Quality/ ; },
mesh = {Humans ; *Quality of Life/psychology ; Female ; Male ; *COVID-19/psychology/epidemiology ; Child ; Retrospective Studies ; Adolescent ; *Anxiety/epidemiology/psychology ; *Depression/epidemiology/psychology ; Comorbidity ; Prevalence ; },
abstract = {OBJECTIVE: Up to 25% of youth may develop long COVID following COVID-19 infection. Mood changes are commonly reported; however, few studies use validated measures. This study describes prevalence of self-reported anxious and depressive symptoms among youth with long COVID. We also examined the association of these symptoms with prior mental health diagnosis and health-related quality of life.<br><br>METHODS: We conducted a retrospective study of pediatric patients (n&#x2009;=&#x2009;139) evaluated in a pediatric post-COVID-19 rehabilitation clinic who met criteria for long COVID. Patients were included if they completed the Pediatric Quality of Life Inventory (PedsQL), the Multidimensional Anxiety Scale for Children, second edition (MASC 2), and/or the Children's Depression Inventory, second edition (CDI 2). Relationships between prior anxiety or mood disorder and current depressive and anxious symptoms were assessed using chi-square tests. Relationships between depressive and anxious symptoms and health-related quality of life were examined using multiple linear regression.<br><br>RESULTS: Almost 40% of patients had elevated scores for anxious or depressive symptoms. Prior anxiety or mood disorder diagnosis was associated with higher scores. Depression scores, and specifically the Ineffectiveness subscale, were inversely associated with PedsQL scores.<br><br>CONCLUSIONS: Prevalence of anxious and depressive symptoms in this clinical sample was high. Screening measures for mood and anxiety overlap with physical symptoms of long COVID and use of collateral information is recommended. The relationship between the Ineffectiveness subscale and the PedsQL warrants further investigation to evaluate if they assess the same domain or if negative perception of abilities contributes to health-related quality of life.},
}
@article {pmid40327434,
year = {2025},
author = {Kraft, J and Hardy, A and Baustädter, V and Bögel-Witt, M and Krassnig, K and Ziegler, B and Waibl, PJ and Meissner, K},
title = {Traditional Chinese medicine for post-COVID: A retrospective cohort study.},
journal = {Medicine},
volume = {104},
number = {18},
pages = {e42275},
pmid = {40327434},
issn = {1536-5964},
support = {//Association for Classical Acupuncture and Traditional Chinese Medicine (AGTCM), Vienna School of Traditional Chinese Medicine (WSTCM)/ ; },
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *COVID-19/complications/therapy ; *Medicine, Chinese Traditional/methods ; Middle Aged ; Adult ; Aged ; SARS-CoV-2 ; Acupuncture Therapy/methods ; Post-Acute COVID-19 Syndrome ; Germany ; Treatment Outcome ; Surveys and Questionnaires ; Austria ; },
abstract = {Post-COVID syndrome affects at least 10% of individuals recovering from COVID-19. Currently, there is no causal treatment. This retrospective cohort study aimed to evaluate the potential of traditional Chinese medicine (TCM) in treating post-COVID symptoms. TCM physicians in Germany and Austria completed online questionnaires to retrospectively record symptoms, treatment approaches, and outcomes for patients diagnosed with post-COVID. Nine physicians collected data from 79 patients (65% female, 47 ± 16 SD). The most common TCM treatments for post-COVID were acupuncture (n = 66; 85%), Chinese pharmacological therapy (n = 61; 77%), and Chinese dietary counseling (n = 32; 41%). After an average of 7 ± 4 TCM consultations, physicians rated global symptom improvement as 62% ± 29%. Significant alleviation from the start of TCM treatment was observed in major symptoms, such as fatigue (P < .001), impaired physical performance (P < .001), and exertional dyspnea (P < .001). TCM treatment was associated with significant improvements in post-COVID symptoms, warranting further evaluation through randomized controlled studies.},
}
@article {pmid40326310,
year = {2025},
author = {El-Naas, A and Hamad, O and Nair, S and Alfakhri, B and Mahmoud, S and Haji, A and Ahmed, L and Lebbe, A and Aboulwafa, A and Shaikh, F and Bouhali, I and Zakaria, D},
title = {New onset of type 1 and type 2 diabetes post-COVID-19 infection: a systematic review.},
journal = {Emerging microbes &amp; infections},
volume = {14},
number = {1},
pages = {2492211},
pmid = {40326310},
issn = {2222-1751},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus, Type 1/epidemiology/etiology ; *Diabetes Mellitus, Type 2/epidemiology/etiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; },
abstract = {COVID-19 may primarily cause respiratory symptoms but can lead to long-term effects known as long COVID. COVID-19-induced diabetes mellitus was reported in many patients which shares characteristics of types 1 and 2 (T1DM and T2DM). This study aims to identify and analyse the reported cases of new onset diabetes post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of T1DM or T2DM post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 43 studies met our inclusion criteria. Our results revealed that the overall prevalence of new onset diabetes post-COVID-19 was 1.37% with higher prevalence for T2DM (0.84%) as compared to T1DM (0.017%) while the type of diabetes was not reported in 0.51% of the cases. Several risk factors for developing diabetes post-COVID-19 infection were identified including the type of SARS-CoV-2 variant, age, comorbidities, and the vaccination status. The direct viral attack of the pancreatic beta cells as well as inflammation and the anti-inflammatory corticosteroids were proposed as possible mechanisms of the COVID-19 induced diabetes. A multidisciplinary approach involving endocrinologists, primary care physicians, and infectious disease specialists should be implemented in the management of post-COVID patients to address both the acute and long-term complications, including metabolic changes and risk of diabetes.},
}
@article {pmid40325669,
year = {2025},
author = {Karnadipa, T and Pratama, AD and Pahlawi, R and Noviana, M and Yu, CW and Caraka, RE and Wan, Y},
title = {Clinical indicators for predicting physical activity levels in long-term COVID-19: Insights from physical exertion and oxygen saturation.},
journal = {Journal of bodywork and movement therapies},
volume = {42},
number = {},
pages = {198-204},
doi = {10.1016/j.jbmt.2024.11.031},
pmid = {40325669},
issn = {1532-9283},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Adult ; Male ; Cross-Sectional Studies ; Female ; Middle Aged ; *Exercise/physiology ; *Physical Exertion/physiology ; *Oxygen Saturation/physiology ; Heart Rate/physiology ; SARS-CoV-2 ; Dyspnea/physiopathology ; Young Adult ; Oxygen Consumption/physiology ; },
abstract = {INTRODUCTION: Long COVID-19 syndrome, affecting approximately 80% of adults after SARS-CoV-2 infection, often reduces physical activity due to fatigue and breathing difficulties, leading to impaired physical function and lung capacity. This cross-sectional study examined predictive variables such as physical exertion, heart rate, and oxygen saturation to assess physical activity levels in adults with long COVID-19 syndrome.<br><br>METHODS: We recruited 34 adults aged 19-55 with a COVID-19 history and assigned them to the long-COVID-19 and control group. They were evaluated using the 6-Minute Walk Test, modified Borg Dyspnoea Scale, heart rate, maximum oxygen uptake, and the IPAQ-Short Form for daily physical activity assessment.<br><br>RESULTS: The Borg Dyspnoea Scale, maximum oxygen uptake, and resting oxygen saturation emerged as crucial indicators for predicting physical activity levels in post-COVID-19 individuals. Compared to these variables, resting and post-exercise heart rates were statistically insignificant.<br><br>CONCLUSION: Physical exertion and oxygen saturation are potentially crucial predictors of physical activity levels in individuals with persistent post-COVID-19 symptoms. These findings offer valuable insights for managing long COVID-19 syndrome, emphasising the need for tailored interventions to address reduced physical activity levels in affected individuals.},
}
@article {pmid40325175,
year = {2025},
author = {Rovito, R and Bono, V and Coianiz, N and Cazzetta, V and Franzese, S and Mikulak, J and Di Vito, C and Bai, F and Beaudoin-Bussières, G and Tauzin, A and Augello, M and Tincati, C and Santoro, A and Borghi, E and Marozin, S and Finzi, A and Della Bella, S and Mavilio, D and Marchetti, G and , },
title = {Multi-layered deep immune profiling, SARS-CoV-2 RNAemia and inflammation in unvaccinated COVID-19 individuals with persistent symptoms.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {155},
pmid = {40325175},
issn = {2730-664X},
abstract = {BACKGROUND: Long-COVID immunopathogenesis involves diverse factors. We longitudinally characterize hospitalized COVID-19 patients, examining the role of SARS-CoV-2 RNAemia and inflammation in immune dysregulation.<br><br>METHODS: Hospitalized patients are evaluated during acute infection (T0), 3 months post-symptom onset (T1), and 3 years if symptoms persisted (T2). Immune profile includes characterization of SARS-CoV-2-specific/non-specific T/B cells (flow cytometry) and antibodies (ELISA, neutralization, ADCC). RNAemia and cytokines are quantified (RT-PCR, cytometric beads array) and correlated.<br><br>STATISTICS: non-parametric cross-sectional, longitudinal and correlation analyses.<br><br>RESULTS: Here we show 48 hospitalized individuals during acute COVID-19, 38 exhibit early persistent symptoms (EPS+) 3 months post-symptoms onset, 10 do not (EPS-). Groups are comparable for age, sex, co-morbidities. The EPS+ shows fatigue, dyspnoea, anosmia/dysgeusia, diarrhea, chronic pain, mnestic disorders. Over time, they show a reduction of neutralization ability and total SARS-CoV-2-specific CD4 T cells, with increased total CD4 TEMRA, and failure to increase RBD-specific B cells and IgA+ MBCs. EPS+ patients show higher levels of T0-IFN-&#x3b3;&#x2009;+&#x2009;CD4 TEMRA, T1-IL-2&#x2009;+&#x2009;CD4 TEM and T1-TNF-&#x3b1;&#x2009;+&#x2009;CD4 cTfh. In EPS+, baseline SARS-CoV-2 RNAemia positively correlates with CD4 TEMRA, follow-up SARS-CoV-2 RNAemia with ADCC. Among 38 EPS+ individuals at T1, 33 are evaluated 3 years after infection, 5 are lost at follow-up. 10/33 EPS+ show long-term symptoms (late persistent symptoms, EPS&#x2009;+&#x2009;LPS+), whereas 23/33 fully recover (EPS&#x2009;+&#x2009;LPS-). Antibodies, RNAemia, and cytokines show no differences between/within groups at any time point.<br><br>CONCLUSIONS: Early persistent symptoms are associated with multi-layered SARS-CoV-2-specific/non-SARS-CoV-2-specific immune dysregulation. The shift towards non-Ag-specific TEMRA and ADCC trigger in EPS+ may relate to SARS-CoV-2 RNAemia. Early immune dysregulation does not associate with long-term persistent symptoms. Further research on SARS-CoV-2 RNAemia and early immune dysregulation is needed.},
}
@article {pmid40324362,
year = {2025},
author = {Souza, JA and Pasqualoto, AS and Moraes, DAO and Cielo, CA},
title = {Lung Function, Voice, and Quality of Life in Post-COVID-19 Syndrome: A Follow-Up Study.},
journal = {Folia phoniatrica et logopaedica : official organ of the International Association of Logopedics and Phoniatrics (IALP)},
volume = {},
number = {},
pages = {1-17},
doi = {10.1159/000546258},
pmid = {40324362},
issn = {1421-9972},
abstract = {INTRODUCTION: COVID-19 sequelae may persist for years, particularly in individuals who experienced critical illness. This longitudinal study aimed to assess lung function, voice, and their correlation in post-COVID-19 syndrome (PCS) patients after intensive care discharge and evaluate the impact on general and voice-related quality of life (V-RQoL).<br><br>METHODS: Among the 284 patients who survived hospitalization at the University Hospital, 48 met the inclusion and exclusion criteria and participated in the study. Evaluations were conducted at an average of 4 and 8 months post-discharge and included assessments of dyspnea (modified Medical Research Council [mMRC] scale), spirometry, inspiratory (MIP), and expiratory (MEP) muscle strength, the 6-minute walk test (6MWT), maximum phonation time (MPT), sound pressure level (SPL), overall degree of dysphonia, general quality of life (Short Form Health Survey [SF-36]), and V-RQoL.<br><br>RESULTS: There was a reduction in mMRC, and an increase in MIP, MEP, 6MWT, MPT, and usual and minimum SPL. Women still exhibited reduced MPT, and both sexes had persistent dysphonia. A negative correlation was found between mMRC and MPT, and a positive correlation was found between 6MWT and MPT. Some SF-36 domains and the physical score of the V-RQoL for women remained reduced.<br><br>CONCLUSIONS: Eight months after COVID-19, there was an improvement in pulmonary function and MPT, but an increase in usual and minimum SPL and persistent dysphonia. These findings highlight the need for further research into persistent dysphonia as a significant aspect of PCS.},
}
@article {pmid40322881,
year = {2025},
author = {Vieira Junior, JCA and Sander, MRL and Matos, JAO and Medeiros, AM and Silva, FSD and Aires, CAM},
title = {Neurological Post-Acute Sequelae of COVID-19 in Non-Hospitalized Patients: An Integrative Review.},
journal = {Biological research for nursing},
volume = {27},
number = {4},
pages = {652-665},
doi = {10.1177/10998004251335968},
pmid = {40322881},
issn = {1552-4175},
mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/etiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {The COVID-19 pandemic has had a significant impact on the global population. The infection, caused by SARS-CoV-2, presents with a variety of clinical manifestations, from asymptomatic cases to more severe forms, including a variety of neurological symptoms, such as fatigue, weakness, brain fog, paresthesias, dysautonomia, anosmia, and dysgeusia. Additionally, the disease is associated with the long COVID syndrome, in which there is persistence of the effects and symptoms of the acute phase. In recent years the literature has shown relevant data on long COVID, but there is still a need to deepen the knowledge about these long term manifestations. Thus, the present study aimed to describe the main neurological sequelae resulting from SARS-CoV-2 infection in non-hospitalized population during the long phase of the disease, gathering scientific evidence through an integrative review of the prevalence of symptoms, patient profile, duration and severity of sequelae, risk factors, comorbidities, and possible nervous system structural damage. The PubMed/Medline database was used with descriptors and, at the end of the screening process with predefined inclusion and exclusion criteria, 22 studies were included. A group of neurological symptoms associated with long COVID was identified: myalgia, dysgeusia, memory alterations, olfactory dysfunction, dizziness, and pain. Most patients presented multiple symptoms that lasted for more than one year with a significant impact on quality of life. The main risk factors were dyslipidemia, age, ethnicity, muscle/ joint pain, and sex. This review highlights the importance of further studies on the syndrome, its etiology, diagnosis, follow-up, and treatments.},
}
@article {pmid40322318,
year = {2025},
author = {Bui, DP and Bast, E and Trinh, H and Fox, A and Berkowitz, TSZ and Palacio, A and Wander, PL and O'Hare, AM and Boyko, EJ and Ioannou, GN and Maciejewski, ML and Hynes, DM},
title = {Use of Long COVID Clinics in the Veterans Health Administration: Implications for the path forward.},
journal = {Health affairs scholar},
volume = {3},
number = {5},
pages = {qxaf080},
pmid = {40322318},
issn = {2976-5390},
support = {IK6 HX003395/HX/HSRD VA/United States ; },
abstract = {Long COVID is a serious chronic illness that can present in many forms and impact daily functioning and quality of life. Without curative treatments, management of long COVID requires coordination and ongoing access to multidisciplinary care. Starting in 2020, the Veterans Health Administration (VHA), established a national network of Long COVID Clinics (LCCs). In this retrospective cohort study of 494 547 veterans with documented SARS-CoV-2 infection in the VHA from March 2020 to April 2022 (n = 494 547), we examined trends in ICD-10 U09.9 diagnosis code use for long COVID and LCC use in the VHA up to May 2024. Overall, 5.9% (n = 29 195) of patients in our cohort had a documented U09.9 code and 2% had at least 1 LCC visit. Among veterans with a U09.9 code, 17.4% (n = 5089) used LCCs. LCC use rates were low across all patient subgroups. LCCs were more available to veterans residing in the South census region (28% vs <7% use rate) than veterans in other regions. Developing evidence about LCC effectiveness and ensuring equitable access to LCCs within and beyond the VHA will be critical in meeting the evolving needs of people with long COVID.},
}
@article {pmid40321289,
year = {2025},
author = {Lage, SL and Bricker-Holt, K and Rocco, JM and Rupert, A and Donovan, FX and Abramzon, YA and Chandrasekharappa, SC and McNinch, C and Cook, L and Amaral, EP and Rosenfeld, G and Dalhuisen, T and Eun, A and Hoh, R and Fehrman, E and Martin, JN and Deeks, SG and Henrich, TJ and Peluso, MJ and Sereti, I},
title = {Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40321289},
abstract = {SARS-CoV-2 can cause a variety of post-acute sequelae including Long COVID19 (LC), a complex, multisystem disease characterized by a broad range of symptoms including fatigue, cognitive impairment, and post-exertional malaise. The pathogenesis of LC is incompletely understood. In this study, we performed comprehensive cellular and transcriptional immunometabolic profiling within a cohort that included SARS-CoV-2-naïve controls (NC, N=30) and individuals with prior COVID-19 (~4-months) who fully recovered (RC, N=38) or went on to experience Long COVID symptoms (N=58). Compared to the naïve controls, those with prior COVID-19 demonstrated profound metabolic and immune alterations at the proteomic, cellular, and epigenetic level. Specifically, there was an enrichment in immature monocytes with sustained inflammasome activation and oxidative stress, elevated arachidonic acid levels, decreased tryptophan, and variation in the frequency and phenotype of peripheral T-cells. Those with LC had increased CD8 T-cell senescence and a distinct transcriptional profile within CD4 and CD8 T-cells and monocytes by single cell RNA sequencing. Our findings support a profound and persistent immunometabolic dysfunction that follows SARS-CoV-2 which may form the pathophysiologic substrate for LC. Our findings suggest that trials of therapeutics that help restore immune and metabolic homeostasis may be warranted to prevent, reduce, or resolve LC symptoms.},
}
@article {pmid40321247,
year = {2025},
author = {Zhang, S and Jahanbani, F and Chander, V and Kjellberg, M and Liu, M and Glass, KA and Iu, DS and Ahmed, F and Li, H and Maynard, RD and Chou, T and Cooper-Knock, J and Zhang, MJ and Thota, D and Zeineh, M and Grenier, JK and Grimson, A and Hanson, MR and Snyder, MP},
title = {Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40321247},
support = {U54 AI178855/AI/NIAID NIH HHS/United States ; U54 NS105541/NS/NINDS NIH HHS/United States ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogeneous, and systemic disease defined by a suite of symptoms, including unexplained persistent fatigue, post-exertional malaise (PEM), cognitive impairment, myalgia, orthostatic intolerance, and unrefreshing sleep. The disease mechanism of ME/CFS is unknown, with no effective curative treatments. In this study, we present a multi-site ME/CFS whole-genome analysis, which is powered by a novel deep learning framework, HEAL2. We show that HEAL2 not only has predictive value for ME/CFS based on personal rare variants, but also links genetic risk to various ME/CFS-associated symptoms. Model interpretation of HEAL2 identifies 115 ME/CFS-risk genes that exhibit significant intolerance to loss-of-function (LoF) mutations. Transcriptome and network analyses highlight the functional importance of these genes across a wide range of tissues and cell types, including the central nervous system (CNS) and immune cells. Patient-derived multi-omics data implicate reduced expression of ME/CFS risk genes within ME/CFS patients, including in the plasma proteome, and the transcriptomes of B and T cells, especially cytotoxic CD4 T cells, supporting their disease relevance. Pan-phenotype analysis of ME/CFS genes further reveals the genetic correlation between ME/CFS and other complex diseases and traits, including depression and long COVID-19. Overall, HEAL2 provides a candidate genetic-based diagnostic tool for ME/CFS, and our findings contribute to a comprehensive understanding of the genetic, molecular, and cellular basis of ME/CFS, yielding novel insights into therapeutic targets. Our deep learning model also offers a potent, broadly applicable framework for parallel rare variant analysis and genetic prediction for other complex diseases and traits.},
}
@article {pmid40320865,
year = {2025},
author = {Leggat, F and Torrens-Burton, A and Sewell, B and Sevdalis, N and Busse, M and Domeney, A and Parsons, J and Abreu, MIS and Jones, F},
title = {Personalisation at the Core of Success: Process Evaluation of the LISTEN Randomised Controlled Trial Evaluating a Personalised Self-Management Support Intervention for People Living With Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70270},
pmid = {40320865},
issn = {1369-7625},
support = {//This study is independent research funded by the National Institute for Health and Care Research (NIHR) [Long Covid Personalised Self-managemenT support co-design and EvaluatioN (LISTEN), COV-LT2-0009]. Authors are chief investigators or co-investigators on various current research grants from the UK NIHR. The Centre for Trials Research receives infrastructure funding from Health and Care Research Wales. PRIME Centre Wales and the former Wales Covid-19 Evidence Centre (now Health and Care Research Wales Evidence Centre) receive infrastructure funding from Health and Care Research Wales. Up until March 2024, F.J.'s research was supported by the NIHR Applied Research Collaboration South London at King's College Hospital NHS Foundation Trust./ ; },
mesh = {Humans ; *COVID-19/rehabilitation ; *Self-Management/methods ; England ; Female ; Male ; State Medicine ; Wales ; SARS-CoV-2 ; Focus Groups ; Middle Aged ; },
abstract = {BACKGROUND: The development and evaluation of rehabilitation interventions designed to support people with Long Covid (LC) remains an important ongoing priority. Many people with LC experience episodic, debilitating symptoms that can reduce their ability to engage in all areas of activity. The Long CovId personalised Self-managemenT support co-design and EvaluatioN (LISTEN) trial co-designed and evaluated a personalised self-management support intervention to build confidence and support people to live better with LC. This paper describes the context, implementation, mechanisms of impact and impacts from the LISTEN intervention, in comparison with usual LC services accessed within the National Health Service (NHS).<br><br>METHODS: A mixed methods process evaluation was nested within the LISTEN pragmatic, multi-site, randomised controlled trial. Data were collected from sites in England and Wales between September 2022 and January 2024. Observations and focus groups with healthcare practitioners (HCPs) delivering the intervention were conducted to assess fidelity. Standardised implementation measures, focussed on intervention feasibility, acceptability and appropriateness, were gathered from HCPs and intervention participants. Semi-structured interviews were undertaken with a subset of participants across both trial arms. Data were analysed independently using descriptive statistics, or reflexive thematic analyses, and subsequently integrated, drawing upon the Consolidated Framework for Implementation Research v2.<br><br>FINDINGS: Thirty-six HCPs participated in the process evaluation, and 197 intervention participants completed standardised implementation measures. Across both trial arms, 49 participants took part in semi-structured interviews. Six integrated themes were constructed from all data sources describing and illustrating links between the context, implementation, mechanisms of impact and impacts: 'Delivery during uncertainty and ambiguity', 'Diversity and consistency of usual care', 'Drivers for self-care and the impact of self-generated expertise', 'Appropriate if unexpected support', 'Personalisation at the core of success' and 'A spectrum of change'.<br><br>CONCLUSION: The LISTEN intervention is an appropriate, feasible intervention for participants and HCPs. The intervention can be delivered to a high level of fidelity following training and with ongoing HCP support. Access, receipt and perceptions of NHS LC services were variable. Personalised, relational interventions, such as LISTEN, can foster favourable impacts on confidence, knowledge and activity and are acceptable and strongly recommended within LC rehabilitation services.<br><br>The study was supported by a patient and public involvement and engagement (PPIE) group from project conception to study end. Using their lived expertise, seven people with LC supported accessible recruitment (e.g., materials), data collection (e.g., topic guides), data interpretation (e.g., theme construction and reviewing findings) and dissemination activities (e.g., online webinars).<br><br>TRIAL REGISTRATION: ISRCTN36407216, registered 27/01/2022.},
}
@article {pmid40318391,
year = {2025},
author = {Samanci, B and Ay, U and Gezegen, H and Yörük, SS and Medetalibeyoğlu, A and Kurt, E and Şahin, E and Doğan, FU and Barbüroğlu, M and Bilgiç, B and Hanağası, H and Gürvit, H},
title = {Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {187},
number = {},
pages = {98-110},
doi = {10.1016/j.cortex.2025.04.004},
pmid = {40318391},
issn = {1973-8102},
mesh = {Humans ; Male ; *COVID-19/complications/physiopathology/diagnostic imaging/psychology ; Female ; Magnetic Resonance Imaging ; Middle Aged ; Adult ; Cross-Sectional Studies ; *Brain/diagnostic imaging/physiopathology/pathology ; Neuropsychological Tests ; *Cognitive Dysfunction/physiopathology/diagnostic imaging/etiology ; SARS-CoV-2 ; Gray Matter/diagnostic imaging/pathology ; *Nerve Net/diagnostic imaging/physiopathology ; },
abstract = {This study aimed to investigate the neurocognitive deficits, structural brain alterations, and network abnormalities in individuals who had a mild SARS-CoV-2 infection, with and without brain fog, as a symptom of long COVID. A cross-sectional study was conducted involving 75 participants, categorized into three groups: 24 healthy controls (HCs), 26 COVID-19 survivors without brain fog (woFOG), and 25 with brain fog (wFOG). Neuropsychological assessments included the Free and Cued Selective Reminding Test (FCSRT) and Addenbrooke's Cognitive Examination-Revised (ACE-R). Structural and functional brain alterations were examined using voxel-based morphometry (VBM) and resting-state functional MRI (rs-fMRI). The wFOG group exhibited significant cognitive impairments, particularly in delayed free recall, attention, memory, and visuospatial skills, compared to both the woFOG and HC groups. Structural MRI analyses revealed reduced gray matter concentrations (GMC) in the left inferior temporal gyrus, left fusiform gyrus, and right orbital gyri in both COVID-19 groups relative to HCs. Additionally, the wFOG group exhibited further GMC reductions in the bilateral caudate nuclei, right putamen/pallidum, and amygdala compared to the woFOG group. rs-fMRI analyses demonstrated altered connectivity patterns in COVID-19 survivors, characterized by increased connectivity in the default mode network and visual networks, alongside decreased connectivity in the dorsal attention network. These findings indicate that even mild COVID-19 can result in persistent neurocognitive deficits, structural brain alterations, and functional network abnormalities, both in individuals with and without brain fog. The observed changes highlight the importance of long-term monitoring and targeted interventions to address potential cognitive and neurological consequences of long COVID.},
}
@article {pmid40317182,
year = {2025},
author = {Louvrier, M and Saussez, S and Lechien, JR},
title = {Psychological Distress in Patients with Long-lasting COVID-19 Olfactory Dysfunction.},
journal = {Journal of otolaryngology - head &amp; neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale},
volume = {54},
number = {},
pages = {19160216251328960},
pmid = {40317182},
issn = {1916-0216},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Female ; *Olfaction Disorders/psychology/etiology/epidemiology ; Middle Aged ; *Psychological Distress ; Adult ; Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Belgium/epidemiology ; },
abstract = {ObjectiveThe aim of this study was to investigate the psychological distress associated with long-lasting COVID-19 olfactory dysfunction (OD).MethodsPatients with an OD lasting for more than 6 months were consecutively recruited from the Dour Medical Center (Belgium) from August 2023 to January 2024. The olfaction was investigated with the Olfactory Disorder Questionnaires (ODQ) and the threshold, identification, and discrimination (TDI) testing. General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) were used to investigate the psychological distress of patients. The olfactory and psychological outcomes of patients were compared with a group of individuals without OD.ResultsA total of 220 patients and 102 asymptomatic individuals completed the evaluations. The mean duration of OD was 31.1 ± 25.1 months. The mean GAD-7 and PHQ-9 scores were significantly higher in OD patients than in asymptomatic individuals (P < 0.008). The OD patient prevalence of mild-to-severe depression (51.2% vs. 44.1%) and mild-to-severe anxiety (39.5% vs. 32.4%) disorders was significantly higher than asymptomatic individuals. Severe anxiety was associated with the presence of anosmia. GAD-7 and PHQ-9 scores were higher in females than in males. The severity of depression (PHQ-9) and anxiety (GAD-7) was significantly associated with the severity of OD (ODQ) and nasal symptoms (SNOT-22).ConclusionThe presence of a long-lasting OD in patients consulting in otolaryngology is associated with psychological distress. While the causality relationship remains unclear, depression and anxiety symptoms must be investigated in this subgroup of patients with long COVID-19.},
}
@article {pmid40316182,
year = {2025},
author = {van Leeuwen, LPM and Van Coillie, S and Prévot, J and Drabwell, J and Mahlaoui, N and Sánchez-Ramón, S and Poli, MC and Meyts, I and Ali, A and Lowe, DM and Dalm, VASH and Pergent, M},
title = {Long-term effects of COVID-19 in patients with primary immunodeficiency: An IPOPI worldwide survey.},
journal = {The Journal of allergy and clinical immunology},
volume = {156},
number = {2},
pages = {449-462},
doi = {10.1016/j.jaci.2025.04.023},
pmid = {40316182},
issn = {1097-6825},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Quality of Life ; Adult ; *SARS-CoV-2 ; Middle Aged ; *Primary Immunodeficiency Diseases/epidemiology ; Prevalence ; Risk Factors ; Young Adult ; Adolescent ; Surveys and Questionnaires ; Aged ; Child ; Comorbidity ; },
abstract = {BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, many individuals developed persistent symptoms after COVID-19. The data on these long-term effects in the primary immunodeficiency (PID) community are limited.<br><br>OBJECTIVE: This study aimed to understand long-term symptoms after COVID-19 in patients with PID, focusing on prevalence, risk factors, viral persistence, and the impact of COVID-19 on their health-related quality of life (HR-QoL).<br><br>METHODS: A global, multilingual web-based survey was conducted by the International Patient Organization for Primary Immunodeficiencies between July and October 2023. Self-reported data on demographics, PID diagnosis, comorbidities, COVID-19, and HR-QoL were collected using the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) survey and analyzed.<br><br>RESULTS: Of the 1160 respondents, 25% reported persistent symptoms after COVID-19. Common symptoms included fatigue, headache, and nasal symptoms. Compared with those respondents without persistent symptoms, those with persistent symptoms after COVID-19 reported a significantly higher prevalence of symptoms across all categories-systemic, pain, cardiopulmonary, gastrointestinal, neurologic, psychological, neurocognitive, and others-except for upper respiratory tract symptoms. Independent risk factors for development of persistent symptoms included female sex, asthma, neurologic diseases, and predominantly antibody deficiency other than common variable immunodeficiency or agammaglobulinemia. In 30% of patients with persistent symptoms, viral clearance was not achieved within 1 month. During the pandemic, HR-QoL declined across all PID categories-even in those without COVID-19, but especially in those with a symptom duration of more than 6 months.<br><br>CONCLUSION: Persistent symptoms after COVID-19 are prevalent among patients with PID, with various risk factors identified. The COVID-19 pandemic had a considerable impact on the HR-QoL of patients with PID regardless of COVID-19 status.},
}
@article {pmid40313298,
year = {2025},
author = {Guzmán Rivera, J and Zheng, H and Richlin, B and Suarez, C and Gaur, S and Ricciardi, E and Hasan, UN and Cuddy, W and Singh, AR and Bukulmez, H and Kaelber, DC and Kimura, Y and Brady, PW and Wahezi, D and Rothschild, E and Lakhani, SA and Herbst, KW and Hogan, AH and Salazar, JC and Moroso-Fela, S and Roy, J and Kleinman, LC and Horton, DB and Moore, DF and Gennaro, ML},
title = {Combining Mass Spectrometry with Machine Learning to Identify Novel Protein Signatures: The Example of Multisystem Inflammatory Syndrome in Children.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40313298},
support = {R33 HD105613/HD/NICHD NIH HHS/United States ; UM1 TR004789/TR/NCATS NIH HHS/United States ; R61 HD105613/HD/NICHD NIH HHS/United States ; R61 HD105593/HD/NICHD NIH HHS/United States ; R33 HD105619/HD/NICHD NIH HHS/United States ; R61 HD105619/HD/NICHD NIH HHS/United States ; R33 HD105593/HD/NICHD NIH HHS/United States ; R01 AI158911/AI/NIAID NIH HHS/United States ; },
abstract = {OBJECTIVES: We demonstrate an approach that integrates biomarker analysis with machine learning to identify protein signatures, using the example of SARS-CoV-2-induced Multisystem Inflammatory Syndrome in Children (MIS-C).<br><br>METHODS: We used plasma samples collected from subjects diagnosed with MIS-C and compared them first to controls with asymptomatic/mild SARS-CoV-2 infection and then to controls with pneumonia or Kawasaki disease. We used mass spectrometry to identify proteins. Support vector machine (SVM) algorithm-based classification schemes were used to analyze protein pathways. We assessed diagnostic accuracy using internal and external cross-validation.<br><br>RESULTS: Proteomic analysis of a training dataset containing MIS-C (N=17), and asymptomatic/mild SARS-CoV-2 infected control samples (N=20) identified 643 proteins, of which 101 were differentially expressed. Plasma proteins associated with inflammation and coagulation increased and those associated with lipid metabolism decreased in MIS-C relative to controls. The SVM machine learning algorithm identified a three-protein model (ORM1, AZGP1, SERPINA3) that achieved 90.0% specificity, 88.2% sensitivity, and 93.5% area under the curve (AUC) distinguishing MIS-C from controls in the training set. Performance was retained in the validation dataset utilizing MIS-C (N=17) and asymptomatic/mild SARS-CoV-2 infected control samples (N=10) (90.0% specificity, 84.2% sensitivity, 87.4% AUC). We next replicated our approach to compare MIS-C with similarly presenting syndromes, such as pneumonia (N=17) and Kawasaki Disease (N=13) and found a distinct three-protein signature (VWF, SERPINA3, and FCGBP) that accurately distinguished MIS-C from the other conditions (97.5% specificity, 89.5% sensitivity, 95.6% AUC). We also developed a software tool that may be used to evaluate other protein pathway signatures using our data.<br><br>CONCLUSIONS: We used MIS-C, a novel hyperinflammatory illness, to demonstrate that the use of mass spectrometry to identify candidate plasma proteins followed by machine learning, specifically SVM, is an efficient strategy for identifying and evaluating biomarker signatures for disease classification.},
}
@article {pmid40313290,
year = {2025},
author = {Butzin-Dozier, Z and Ji, Y and Wang, LC and Anzalone, AJ and Coyle, J and Phillips, RV and Patel, RC and Sun, J and Hurwitz, E and Deshpande, S and Shi, JS and Mertens, A and van der Laan, MJ and Colford, JM and Hubbard, AE},
title = {COVID-19 Vaccination Timing, Relative to Acute COVID-19, and Subsequent Risk of Long COVID.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40313290},
support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U01 DA055358/DA/NIDA NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; K01 AI182501/AI/NIAID NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; INV-018455/GATES/Gates Foundation/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; },
abstract = {OBJECTIVES: Long COVID is a debilitating condition that impacts millions of Americans, but patients and clinicians have little information on how to prevent this disorder. Vaccination is a vital tool in preventing acute COVID-19 and may confer additional protection against Long COVID. There is limited evidence regarding the optimal timing of COVID-19 vaccination (i.e., vaccination schedule) to minimize the risk of Long COVID.<br><br>METHODS: We applied Longitudinal Targeted Maximum Likelihood Estimation to electronic health record (EHR) data from a retrospective cohort of patients vaccinated against COVID-19 between December 2021 and September 2022. We evaluated the association between binary COVID-19 vaccination status (two or more doses vs. zero doses) and 12-month Long COVID risk among patients diagnosed with acute COVID-19 between December 2021 and September 2022. In addition, we compared the 12-month cumulative risk of Long COVID (ICD-10 code U09.9) among patients diagnosed with acute COVID-19 one to three months after vaccination, three to five months after vaccination, or five to seven months after vaccination while adjusting for relevant high-dimensional baseline and time-dependent covariates.<br><br>RESULTS: We analyzed EHR data from a retrospective cohort of 1,558,018 patients. In our binary cohort (n = 519,980), we found that vaccinated patients had a lower risk of Long COVID than unvaccinated patients (adjusted marginal risk ratio 0.84 (0.81, 0.88)). In our longitudinal cohort (n = 1,085,291), we did not find a significant difference in Long COVID risk comparing patients who were diagnosed with acute COVID-19 one to three months after vaccination versus patients who were diagnosed with COVID-19 three to five months (adjusted marginal risk ratio 0.93 (95% CI 0.62, 1.41) or 5 to 7 months (adjusted marginal risk ratio 1.06 (95% CI 0.72, 1.56)) after vaccination.<br><br>CONCLUSIONS: We found that COVID-19 vaccination before SARS-CoV-2 infection was protective against Long COVID, and we did not find that this protection significantly waned within 7 months after vaccination. These findings suggest that COVID-19 vaccination protects against Long COVID.},
}
@article {pmid40313005,
year = {2025},
author = {Nakagawa, F and Palich, R and Kall, M and Sewell, J and Smith, C and Kelly, C and Kitt, H and Pelchen-Matthews, A and Aghaizu, A and Sparrowhawk, A and Mackie, N and Djuretic, T and Schoeman, S and Humphreys, C and Lipman, M and Lampe, FC and Rodger, AJ and , },
title = {Impact of COVID-19 and factors associated with long COVID and COVID-19 vaccine uptake in people with HIV in the United Kingdom: Results from Positive Voices 2022.},
journal = {HIV medicine},
volume = {26},
number = {6},
pages = {923-939},
pmid = {40313005},
issn = {1468-1293},
support = {NIHR202038//National Institute for Health Research/ ; //Gilead Sciences/ ; },
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control/psychology ; Female ; Male ; United Kingdom/epidemiology ; Adult ; *HIV Infections/epidemiology/psychology/complications ; *COVID-19 Vaccines/administration &amp; dosage ; Middle Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Young Adult ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Health Services Accessibility ; Risk Factors ; },
abstract = {OBJECTIVES: We assessed the impact of COVID-19, and the prevalence and factors associated with a history of COVID-19 infection, long COVID and incomplete COVID-19 vaccine uptake among people with HIV.<br><br>METHODS: Positive Voices 2022 is a questionnaire study of people accessing HIV care in the United Kingdom (March 2022-April 2023). Logistic regression assessed factors associated with a history of COVID-19 (previous positive test), long COVID among those with a history of COVID-19 (ongoing symptoms, with COVID-19 onset >3&#x2009;months previously) and incomplete COVID-19 vaccine uptake (less than three doses of vaccine), adjusted for: age; gender; ethnicity; and year of HIV diagnosis.<br><br>RESULTS: In all, 4188 participants were included. Commonly reported negative impacts of the pandemic were on social contact (44% of participants), mental health (30%), healthcare access (26%) and financial security (25%). Overall, 2068 of 4188 (49.4%) participants had a history of COVID-19. Of these, 10.8% met criteria for long COVID, associated with female gender, unemployment, financial hardship, earlier HIV diagnosis date, diabetes diagnosis, asthma/chronic obstructive pulmonary disease diagnosis, obesity and symptoms of depression and anxiety. Overall, 95.8% reported having at least one vaccine dose, but 649 (15.7%) participants had incomplete vaccine uptake, associated with younger age, female gender, Black African ethnicity, lower education, financial hardship, unemployment, multioccupancy household, more recent HIV diagnosis, detectable HIV viral load and symptoms of depression and anxiety.<br><br>CONCLUSIONS: About half of participants had a history of COVID-19, of whom 11% had persistent symptoms (long COVID). COVID-19 vaccine uptake was high, but incomplete uptake was apparent for 16% of participants and was more common among women, younger people, Black African individuals and those with socio-economic disadvantage.},
}
@article {pmid40311810,
year = {2025},
author = {Simonetti, A and Bardi, F and Margoni, S and Grisoni, F and Mandracchia, G and Mazza, M and Moccia, L and Kotzalidis, GD and Janiri, D and Tosato, M and Landi, F and Sani, G},
title = {Affective temperament modulates the relationship between physical and psychiatric symptoms during long-COVID: results from the Gemelli against COVID-19 post-acute care service.},
journal = {Journal of affective disorders},
volume = {383},
number = {},
pages = {315-322},
doi = {10.1016/j.jad.2025.04.158},
pmid = {40311810},
issn = {1573-2517},
mesh = {Humans ; *COVID-19/psychology/complications ; *Temperament ; Male ; Female ; Middle Aged ; Adult ; SARS-CoV-2 ; Stress Disorders, Post-Traumatic/psychology ; Aged ; Post-Acute COVID-19 Syndrome ; Irritable Mood ; Psychiatric Status Rating Scales ; Depression/psychology ; Anhedonia ; },
abstract = {BACKGROUND: Affective temperaments represent the substrate of personality that can influence the expression of chronic infectious diseases, including COVID-19 and its sequelae. However, research conducted so far on this topic focused on narrow aspects of psychopathology.<br><br>AIM: To investigate the effect of affective temperaments on the relationship between physical and psychiatric symptoms in patients with long-COVID.<br><br>METHODS: The sample consisted of 1513 patients who have been hospitalized for COVID-19 and developed long-COVID. Participants performed a multidisciplinary assessment including psychiatric evaluation through the administration of rating scales. The psychiatric dimensions assessed included severity of depressive, anxiety, manic symptoms, anhedonia, hopelessness, suicidal risk, psychological distress, levels of well-being, resilience, emotion regulation, and levels of post-traumatic stress disorder (PTSD). Affective temperament was assessed through the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire (TEMPS-A). We used TEMPS-A subscales as moderators and sociodemographic and COVID-19/long-COVID-related clinical characteristics as predictors. Psychiatric rating scales total scores were outcome variables.<br><br>RESULTS: Cyclothymic, irritable, and depressive temperaments strengthened the relationship between number of long-COVID symptoms, levels of anhedonia and poor psychological well-being. Cyclothymic and irritable temperaments weakened the relationship between number of long-COVID symptoms and history of intensive care unit admission and PTSD severity. Depressive temperament strengthened the latter relationship.<br><br>LIMITATION: The clinical variables included in the analyses do not represent the entire range of psychopathology.<br><br>CONCLUSIONS: Depressive temperament enhanced the relationship between physical and psychiatric symptoms in patients with long-COVID, whereas the effects of cyclothymic and irritable temperaments may depend on the psychiatric dimension assessed.},
}
@article {pmid40310228,
year = {2025},
author = {Bontempo, AC and Bontempo, JM and Duberstein, PR},
title = {Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research.},
journal = {Psychological bulletin},
volume = {151},
number = {4},
pages = {399-427},
doi = {10.1037/bul0000473},
pmid = {40310228},
issn = {1939-1455},
support = {//U.S. Department of Health and Human Services; Health Resources and Services Administration/ ; },
mesh = {Humans ; Qualitative Research ; *Disease/psychology ; *Delivery of Health Care ; },
abstract = {The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients' symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients' psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan's (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person's experiences with illness. We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia. Consistent with Linehan's theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay. Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}
@article {pmid40310209,
year = {2025},
author = {Uswatte, G and Taub, E and Ball, K and Mitchell, BS and Blake, JA and McKay, S and Biney, F and Iosipchuk, O and Hempfling, P and Harris, E and Dickerson, A and Lokken, K and Knight, AJ and Mark, VW and Agnihotri, S and Cutter, G},
title = {Long COVID brain fog treatment: An early-phase randomized controlled trial of constraint-induced cognitive therapy signals go.},
journal = {Rehabilitation psychology},
volume = {},
number = {},
pages = {},
pmid = {40310209},
issn = {1939-1544},
support = {R01 AG070049/AG/NIA NIH HHS/United States ; //National Institutes of Health; National Institute on Aging/ ; //National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR)/ ; },
abstract = {PURPOSE: Long COVID brain fog is often disabling. Yet, no empirically supported treatments exist. This study's objectives were to evaluate the feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.<br><br>DESIGN: Sixteen community residents &#x2265;3 months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment as usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive training program. CICT was deemed feasible if (a) &#x2265; 80% of participants were adherent, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) < 2 study-related, serious adverse events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.<br><br>RESULTS: Fourteen completed Immediate-CICT (n = 7) or TAU (n = 7); two withdrew from TAU before their second testing session. Completers were, M (SD): 10 (7) months post-COVID; 51 (13) years old; 10 females, four males; one African American, and 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M = 3.7 points, p < .001, d = 2.6) and brain fog (M = -4 points, p < .001, d = -2.9). Four of five nonretired Immediate-CICT participants returned to work posttreatment; no TAU participants did, p = .048.<br><br>CONCLUSION: Those who received CICT adhered to the protocol and were highly satisfied with their outcomes. The findings warrant a large-scale randomized controlled trial with an active-comparison group. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}
@article {pmid40309909,
year = {2025},
author = {Ni, ZC and Lv, L and Xu, JT and Luo, H and Shao, LC and Chen, JH and Ye, XN and Lin, RF and Wu, XD},
title = {Clinical Characterization of Long COVID Among Chinese Healthcare Workers: A Multicenter, Cross-sectional Study.},
journal = {Journal of occupational and environmental medicine},
volume = {67},
number = {8},
pages = {e576-e581},
doi = {10.1097/JOM.0000000000003413},
pmid = {40309909},
issn = {1536-5948},
mesh = {Humans ; *COVID-19/epidemiology/complications/psychology ; Cross-Sectional Studies ; *Health Personnel/psychology/statistics &amp; numerical data ; Male ; Adult ; Female ; China/epidemiology ; Middle Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVES: Since the outbreak of COVID-19, the pandemic has profoundly affected global health and socioeconomic systems. Many recovered patients continue to experience "long COVID" symptoms, affecting their daily life and work performance.<br><br>METHODS: We utilized questionnaires to investigate long COVID symptoms among healthcare workers and their impact on daily life and work.<br><br>RESULTS: Of the healthcare workers, 17% reported long COVID symptoms. Among these, 64.6% experienced neurological symptoms, 57.3% had psychological symptoms, 43% exhibited respiratory symptoms, 44.4% demonstrated cardiovascular symptoms, 58.8% had musculoskeletal symptoms, 31.8% presented with skin symptoms, 31.8% had endocrine symptoms, 34.3% had digestive symptoms, and 70.7% reported general symptoms.<br><br>CONCLUSIONS: Our study reveals that 17% of healthcare workers experience long COVID, with neurological and psychological symptoms being particularly prominent, significantly impacting their daily life and work.},
}
@article {pmid40309668,
year = {2025},
author = {Cozma, A and Briciu, V and Sitar-Tăut, AV and Leucuţa, D and Sporiş, ND and Lazar, AL and Mălinescu, TV and Ganea, AM and Vlad, CV and Lupşe, M and Fodor, A and Terec, A and Suharoschi, R and Indre, M and Orăşan, OH},
title = {Cardiac Dysfunction and Subclinical Atherosclerosis in Post-COVID-19 Patients.},
journal = {Cardiac failure review},
volume = {11},
number = {},
pages = {e09},
pmid = {40309668},
issn = {2057-7540},
abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is still a burden for healthcare systems worldwide. Now, the focus is not only on acute infections, but also on the long-term effects of COVID-19. The present study aimed to evaluate the impact of SARS-CoV-2 infection on the cardiovascular system, and determine the evolution of these changes over 6 months in patients with mild and moderate COVID-19.<br><br>METHODS: The prospective observational study included 103 patients with mild and moderate COVID-19. The patients underwent an echocardiography and a measurement of the arterial stiffness parameters at baseline and 6 months from the initial assessment.<br><br>RESULTS: The diastolic dysfunction (the left atrium volume) was statistically significant at baseline and at the 6-month follow-up in men with moderate COVID-19. The ejection fraction presented significant differences globally in mild versus moderate COVID-19 (p=0.043) that disappeared at 6-month follow-up. Global longitudinal strain alterations were also found in both mild and moderate COVID-19 cases. Regarding the aortic pulse wave velocity, the SARS-CoV-2 infection did not influence the arterial stiffness. Ventricular arterial coupling was significantly altered in moderate COVID-19 at the 6-month evaluation (p=0.0218). Male patients presented a lower tricuspid annular plane systolic excursion at baseline. Right ventricular systolic dysfunction was more frequent among men. Systolic pulmonary arterial pressure increased significantly only in men with moderate disease. Additionally, statistically significant changes at baseline and at 6 months were found regarding the intima-media thickness.<br><br>CONCLUSION: This study shows the cardiovascular long-term sequelae associated with COVID-19 in mild and moderate cases, and emphasises the appropriate investigations for their diagnosis and follow-up.},
}
@article {pmid40308724,
year = {2025},
author = {Williams, JE and Kim, Y and Moramarco, J},
title = {Research Supports the Integration of Acupuncture in Mainstream Health Care for the Management of Chronic Diseases.},
journal = {Medical acupuncture},
volume = {37},
number = {2},
pages = {106-111},
pmid = {40308724},
issn = {1933-6586},
abstract = {PURPOSE: To address the role of acupuncture in mainstream health care for symptom relief, condition outcome, pain management, and shared therapy in resolving chronic diseases. This article explores how acupuncture education can adapt to meet the standards required for inclusion in conventional health care.<br><br>OBJECTIVES: To discuss the future of acupuncture education and its part in training providers for inclusion in a comprehensive health care system that involves physician acupuncturists and licensed acupuncturists for treating and managing specific chronic diseases. To strategize the future of acupuncture education at an advanced clinical level that fosters incorporating acupuncture therapy into selected allopathic settings. To encourage the recognition of translational research for promoting the acceptance of acupuncture by providers and insurers.<br><br>CONCLUSION: Translational research employs clinical evidence to support acupuncture therapy when incorporated into selected areas of allopathic practices, including pain management, palliative care for patients with end-stage cancer, sleep disorders, anxiety disorders, post-traumatic stress, female hormonal conditions such as premenstrual syndrome and menopausal syndrome, as well as chronic fatigue syndromes including Myalgic encephalomyeltitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Advanced clinical training in acupuncture schools and postgraduate certification courses are required to prepare acupuncturists to safely and effectively provide the specialized integrative acupuncture services needed in these clinical areas.},
}
@article {pmid40308396,
year = {2025},
author = {Wang, S and Salway, RJ and Nicklay, M and Kuo, J},
title = {Effectiveness of Dual Sympathetic Blocks for Sympathetically Mediated Symptoms in Post-acute Sequelae of SARS-CoV-2 (PASC): An Open-Label, Non-randomized Pilot Study.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e81530},
pmid = {40308396},
issn = {2168-8184},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, is a multi-system disorder often involving dysautonomia and pain, linked to persistent sympathetic nervous system hyperactivity. Dual sympathetic blocks (DSBs), including stellate ganglion blocks (SGBs), are minimally invasive procedures that may recalibrate dysregulated sympathetic signaling and alleviate PASC symptoms.<br><br>METHODS: This open-label, non-randomized pilot study included 20 participants with PASC experiencing pain and autonomic symptoms. Participants received right-sided and left-sided SGB procedures one week apart. Symptoms were assessed at baseline, week one, and week four using the Composite Autonomic Symptom Score (COMPASS-31) and Patient-Reported Outcomes Measurement Information System (PROMIS-29) scales.<br><br>RESULTS: Seventeen participants completed the study, demonstrating significant improvements in autonomic dysfunction (38.4% reduction in COMPASS-31 scores, p = 0.0016) and pain interference (48.4% reduction, p < 0.001) by week four. Improvements in sleep quality and fatigue were also significant by week four (p = 0.016 and p = 0.049, respectively). Overall, 88.2% of participants reported symptom relief, and no adverse events were observed.<br><br>CONCLUSIONS: DSBs appear to be a promising intervention for PASC-related dysautonomia and pain. These findings warrant further investigation in larger, randomized controlled trials to confirm efficacy and explore the underlying mechanisms.},
}
@article {pmid40308109,
year = {2025},
author = {Thant, TM and Khandai, AC and Gillan, A and Peace, M and Quinn, D and Levenson, J},
title = {Neuropsychiatric Symptoms of Subacute and Chronic Long COVID.},
journal = {The American journal of psychiatry},
volume = {182},
number = {5},
pages = {498-499},
doi = {10.1176/appi.ajp.25182003},
pmid = {40308109},
issn = {1535-7228},
}
@article {pmid40307449,
year = {2025},
author = {Gao, Y and Cai, C and Adamo, S and Biteus, E and Kamal, H and Dager, L and Miners, KL and Llewellyn-Lacey, S and Ladell, K and Amratia, PS and Bentley, K and Kollnberger, S and Wu, J and Akhirunnesa, M and Jones, SA and Julin, P and Lidman, C and Stanton, RJ and Goepfert, PA and Peluso, MJ and Deeks, SG and Davies, HE and Aleman, S and Buggert, M and Price, DA},
title = {Identification of soluble biomarkers that associate with distinct manifestations of long COVID.},
journal = {Nature immunology},
volume = {26},
number = {5},
pages = {692-705},
pmid = {40307449},
issn = {1529-2916},
support = {2020-06121//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; 2021-01141//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; 2021-04779//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; 2022-01313//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; 2021-06534//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; 2021.0136//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; CG-22 0009//Svenska S&#xe4;llskapet f&#xf6;r Medicinsk Forskning (Swedish Society for Medical Research)/ ; PG-22-0432-H-01//Svenska S&#xe4;llskapet f&#xf6;r Medicinsk Forskning (Swedish Society for Medical Research)/ ; 22 2237 Pj//Cancerfonden (Swedish Cancer Society)/ ; 2019-00969//Karolinska Institutet (Karolinska Institute)/ ; 2021-00513//Karolinska Institutet (Karolinska Institute)/ ; 2022-01719//Karolinska Institutet (Karolinska Institute)/ ; 2022-307//Magnus Bergvalls Stiftelse (Magnus Bergvall Foundation)/ ; P500PB_211069//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; COV-LT2-0041//DH | National Institute for Health Research (NIHR)/ ; },
mesh = {*Post-Acute COVID-19 Syndrome/blood/immunology ; Humans ; Male ; Female ; Adult ; Middle Aged ; United Kingdom ; *Antibodies, Neutralizing/blood ; T-Lymphocytes/immunology ; SARS-CoV-2/physiology ; CD8-Positive T-Lymphocytes/cytology ; Plasma/chemistry ; Proteome/analysis ; Flow Cytometry ; *Biomarkers/analysis ; Sweden ; },
abstract = {Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8[+] T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.},
}
@article {pmid40307448,
year = {2025},
author = {Harker, JA and Thwaites, RS},
title = {Unravelling the interplay between respiratory disease and the immune landscape in long COVID.},
journal = {Nature immunology},
volume = {26},
number = {5},
pages = {640-641},
pmid = {40307448},
issn = {1529-2916},
}
@article {pmid40306969,
year = {2025},
author = {Trivieri, MG and Devesa, A and Robson, PM and Bose, S and Cangut, B and Liao, S and Kaufman, A and Pyzik, R and Fauveau, V and Wood, J and Shpiner, A and Yoo, E and Huang, S and Calcagno, C and Mani, V and Thapi, S and Contreras, J and Nie, K and Kim-Schulze, S and Gnjatic, S and Merad, M and Ghesani, M and Putrino, D and Jacobi, A and Mancini, D and Powell, C and Fayad, ZA},
title = {Prevalence of Persistent Cardiovascular and Pulmonary Abnormalities on PET/MRI and DECT Imaging in Long COVID Patients.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {66},
number = {7},
pages = {1126-1134},
pmid = {40306969},
issn = {1535-5667},
support = {KL2 TR001435/TR/NCATS NIH HHS/United States ; R01 HL071021/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *COVID-19/diagnostic imaging/complications/epidemiology ; Middle Aged ; *Magnetic Resonance Imaging ; Prevalence ; Adult ; *Lung/diagnostic imaging ; *Positron-Emission Tomography ; Aged ; Prospective Studies ; *Positron Emission Tomography Computed Tomography ; },
abstract = {The objective of this study is to describe the prevalence of inflammatory cardiopulmonary findings in a prospective cohort of long coronavirus disease (LC) patients. Methods: Subjects with a history of coronavirus disease 2019 infection, persistent cardiopulmonary symptoms 9-12 mo after initial infection, and a clinical assessment compatible with LC underwent cardiopulmonary [18]F-FDG PET/MRI, dual-energy CT (DECT) of the lungs, and plasma protein analysis (subgroup). A control group that included subjects with a history of acute severe acute respiratory syndrome coronavirus 2 infection but without cardiopulmonary symptoms at recruitment was also characterized. Results: Ninety-eight patients (median age, 48.5 y; 47% men) were enrolled. The most common LC symptom was shortness of breath (80%), and 27% of participants were hospitalized. Of the subjects, 90% presented abnormalities in DECT, with 67% and 59% of participants demonstrating pulmonary infiltrates and abnormal perfusion, respectively. PET/MRI was abnormal for 57% of subjects: 24% showed cardiac involvement suggestive of myocarditis, 22% presented uptake reminiscent of pericarditis, 11% showed periannular uptake, and 30% showed vascular uptake (aortic or pulmonary). There was no myocardial, pericardial, periannular, or pulmonary uptake on the PET/MRI scans of the control group (n = 9). Analysis of plasma protein concentrations showed significant differences between the LC and the control groups. Lastly, the plasma protein profile was significantly different among LC patients with abnormal and normal PET/MRI. Conclusion: In LC subjects evaluated up to a year after coronavirus disease 2019 infection, our results indicate a high prevalence of abnormalities on PET/MRI and DECT, as well as significant differences in the peripheral biomarker profile, which might warrant further monitoring to exclude the development of complications such as pulmonary hypertension and valvular disease.},
}
@article {pmid40306350,
year = {2025},
author = {Vacharathit, V and Pluempreecha, M and Manopwisedjaroen, S and Srisaowakarn, C and Srichatrapimuk, S and Sritipsukho, P and Sritipsukho, N and Thitithanyanont, A},
title = {Persistent IP-10/CXCL10 dysregulation following mild Omicron breakthrough infection: Immune network signatures across COVID-19 waves and implications for mRNA vaccine outcomes.},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {278},
number = {},
pages = {110507},
doi = {10.1016/j.clim.2025.110507},
pmid = {40306350},
issn = {1521-7035},
mesh = {Humans ; *COVID-19/immunology/prevention &amp; control ; *SARS-CoV-2/immunology ; *Chemokine CXCL10/immunology/blood ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/immunology/blood ; Middle Aged ; Male ; Female ; Adult ; mRNA Vaccines/immunology ; Antibodies, Neutralizing/immunology/blood ; Aged ; Vaccines, Synthetic/immunology ; Breakthrough Infections ; },
abstract = {This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. We analyzed samples from 114 mild symptomatic COVID-19 patients across multiple pandemic waves, each dominated by different SARS-CoV-2 variants, at three timepoints: (T1: 2-4 weeks, T2: 3-4 months, T3: 6-8 months post-infection). Persistent IP-10 elevation up to 8 months post-Omicron breakthrough infection suggests sustained low-grade immune activation that appears unique to this wave. Hybrid immunity from Omicron breakthrough infections elicited broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of even mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into post-infection immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.},
}
@article {pmid40305670,
year = {2025},
author = {Aracena, KA and Nwankwo, GC and Lee, CT and Karnik, R and Ventura, I and Douglas, D and Udofia, I and Chen, M and Chelala, L and Im, HK and Strek, ME and Adegunsoye, A},
title = {Transcriptomic Profiling of Long COVID-19 in Patients with Interstitial Lung Disease Reveals Dysregulation of Mitochondrial Oxidative Phosphorylation.},
journal = {American journal of respiratory cell and molecular biology},
volume = {73},
number = {4},
pages = {634-637},
pmid = {40305670},
issn = {1535-4989},
support = {K23 HL146942/HL/NHLBI NIH HHS/United States ; K23HL146942/HL/NHLBI NIH HHS/United States ; },
}
@article {pmid40305533,
year = {2025},
author = {Wang, R and Lin, M and Yu, S and Xue, X and Hu, X and Wang, Z},
title = {Predictors of post-COVID-19 syndrome: a meta-analysis.},
journal = {Journal of infection in developing countries},
volume = {19},
number = {4},
pages = {490-497},
doi = {10.3855/jidc.18574},
pmid = {40305533},
issn = {1972-2680},
mesh = {Female ; Humans ; Male ; Comorbidity ; *COVID-19/complications/diagnosis/epidemiology/virology ; Dyspnea/diagnosis/epidemiology/virology ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/virology ; Prognosis ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; },
abstract = {INTRODUCTION: Post Coronavirus Disease 2019 (COVID-19) Syndrome also known as long COVID-19 would affect survivors of various patients. At present, the evidence for predicting a poor prognosis of COVID-19 remains insufficient. This study aims to explore potential predictors of post-COVID-19 syndrome.<br><br>METHODOLOGY: A systematic review process and meta-analysis method are applied to identify the predictors. Systematic searches were conducted without language restrictions from December 1, 2019, to February 28, 2022, on PubMed, Embase, Google Scholar, Web of Science, and Cochrane Library using specific keywords relevant to our targets. The Newcastle Ottawa Scale observational research tool was used to assess study quality and the R (4.1.1) package meta was used for statistical analysis.<br><br>RESULTS: Our meta-analysis of 14 studies showed that females (OR = 1.42, 95% CI: 1.19-1.70), the severity of patients (OR = 2.43, 95% CI: 1.26-4.68), comorbidity (OR = 2.08, 95% CI: 1.29-3.35), dyspnea (OR = 2.02, 95% CI: 1.34-3.04) associated with a higher risk of post-COVID-19 syndrome.<br><br>CONCLUSIONS: Our study showed that females, the severity of COVID-19, comorbidity, and dyspnea were associated with a higher risk of post-COVID-19 syndrome. More attention should be paid to these factors to prevent and treat post-COVID-19 syndrome.},
}
@article {pmid40304923,
year = {2025},
author = {Millhouse, PW and Bloom, RW and Beckstrand, JN and McClure, ML and Eckmann, MS and Feeko, KJ and Mojica, JJ},
title = {The Ganglia of the Head and Neck: Clinical Relevance for the Interventional Pain Physician.},
journal = {Current pain and headache reports},
volume = {29},
number = {1},
pages = {80},
pmid = {40304923},
issn = {1534-3081},
mesh = {Humans ; *Facial Pain/therapy/physiopathology ; *Pain Management/methods ; Nerve Block/methods ; *Headache/therapy ; *Headache Disorders/therapy ; Clinical Relevance ; },
abstract = {PURPOSE OF REVIEW: The purpose of this article is to provide a comprehensive review of the ganglia of the head and neck and their role in the interventional management of chronic headaches and facial pain disorders.<br><br>RECENT FINDINGS: Interventions targeting the sphenopalatine, stellate and gasserian ganglia are well described in the literature for headaches and facial pain disorders. There is a growing body of evidence supporting use of these techniques for clinical conditions outside of pain such as post-traumatic stress disorder and Long COVID symptoms. These findings increase the potential applications of such procedures, making them more relevant to the interventional physician tasked with managing symptoms in difficult to treat medical conditions. Nerve blocks of the head and neck are used for diagnostic and therapeutic purposes in the management of headaches and facial pain disorders. Headaches, whether acute or chronic, are common pain conditions with a wide-range of etiologies and are often difficult to treat. Chronic facial pain can have a variety of underlying causes, including direct or indirect nerve damage, infection, inflammation, and muscle dysfunction. Traditional pain management strategies such as medications and physical therapy often fail or are associated with significant adverse effects. Interventions such as nerve blocks and neuroablative procedures have shown promise in managing headaches and facial pain by directly targeting the underlying causes. This review article summarizes the most recent evidence regarding the efficacy, safety, applications and limitations of these interventional pain management techniques.},
}
@article {pmid40302048,
year = {2025},
author = {Kulik, GL and Zheng, T and Jolley, SE and Ashktorab, H and Brim, H and Feuerriegel, EM and Hafner, JW and Hess, R and Horne, BD and Hornig, M and Johnson, B and Kim, C and Laiyemo, AO and McComsey, GA and Nikolich, J&#x17d; and Reid, K and Scherry, J and Sherif, ZA and Tran, HG and Verduzco-Gutierrez, M and West, S and Erlandson, KM and , },
title = {Physical Function Differences by COVID-19 Status: A Cross-sectional Analysis From the RECOVER Adult Cohort.},
journal = {Physical therapy},
volume = {105},
number = {7},
pages = {},
pmid = {40302048},
issn = {1538-6724},
support = {UM1TR004409//Utah Clinical and Translation Science Award/ ; UL1 TR002548/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; OT2HL161841/NH/NIH HHS/United States ; K24 AG082527/AG/NIA NIH HHS/United States ; //University of Arizona Strategic Initiatives/ ; UM1 TR004528/TR/NCATS NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; OT2HL161847/NH/NIH HHS/United States ; UM1TR002548//National Center for Advancing Translational Sciences component of the NIH/ ; T32 AI150547/AI/NIAID NIH HHS/United States ; OT2HL156812/NH/NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/physiopathology/rehabilitation ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Retrospective Studies ; Adult ; SARS-CoV-2 ; Aged ; United States ; *Physical Functional Performance ; },
abstract = {IMPORTANCE: Many adults with prior SARS-CoV-2 infection have persistent limitations, but few studies have examined objective physical function impairment that persist longer than 3 months after infection.<br><br>OBJECTIVE: The objective was to characterize physical function impairment among adults with and without SARS-CoV-2 infection.<br><br>DESIGN: This study was a retrospective, cross-sectional analysis.<br><br>SETTING: Researching COVID to Enhance Recovery (RECOVER) initiative, a multi-site observational study in the United States (ClinicalTrials.gov: NCT05172024).<br><br>PARTICIPANTS: Participants were adults &#x2265;18&#xa0;years old with and without SARS-CoV-2 infection.<br><br>EXPOSURES: Groups were defined based on COVID-19 status at enrollment: never diagnosed (control), diagnosed with COVID-19&#x2009;&#x2264;&#x2009;12&#xa0;weeks (recent COVID-19), or&#x2009;>&#x2009;12&#xa0;weeks prior to enrollment (remote COVID-19). The RECOVER-Adult Long COVID Index was used to further characterize by Index &#x2265;12 versus 0.<br><br>MAIN OUTCOMES/MEASURES: Physical function (main outcome) was assessed by number of repetitions on a 30-second sit-to-stand test (30STS).<br><br>RESULTS: 30STS assessments at enrollment were available from 11,578 participants. 30STS repetitions were lowest in the remote COVID-19 group (n&#x2009;=&#x2009;4942) with 11.5 (SD&#x2009;=&#x2009;4.2) repetitions compared to 12.5 (SD&#x2009;=&#x2009;4.7) repetitions among controls (n&#x2009;=&#x2009;1887) or 12.2 (SD&#x2009;=&#x2009;4.5) in recent COVID-19 (n&#x2009;=&#x2009;4698). Remote COVID-19, but not recent COVID-19, was associated with lower physical function in the adjusted model (-0.61 repetitions; SD&#x2009;=&#x2009;0.21). Those with RECOVER Long COVID Research Index &#x2265;12 performed 1.6 (SD&#x2009;=&#x2009;0.2) fewer repetitions than those with an Index equal 0.<br><br>CONCLUSIONS: Physical function impairment did not show clinically meaningful group differences between RECOVER Adult Cohort participants by COVID-19 status, or by Long COVID Index. Individual responses over time or in response to an intervention may be more clinically relevant.<br><br>RELEVANCE: In the RECOVER adult cohort, overall physical function differences by time since COVID-19 or by Long COVID Index were small. Individualized assessments are needed to determine functional impairment following COVID-19 diagnosis and subsequent steps for rehabilitation interventions.},
}
@article {pmid40301791,
year = {2025},
author = {Santoro, A and Bai, F and Greco, MF and Rovito, R and Sala, M and Borghi, L and Piscopo, K and Vegni, E and de Morais Caporali, JF and Marinho, CC and Leite, AS and Santoro, MM and Silberstein, FC and Iannetta, M and Juozapaite, D and Strumiliene, E and Almeida, A and Toscano, C and Quinones, JAR and Carioti, L and Mommo, C and Fanti, I and Incardona, F and Marchetti, G and , },
title = {Short and long-term trajectories of the post COVID-19 condition: Results from the EuCARE POSTCOVID study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {625},
pmid = {40301791},
issn = {1471-2334},
support = {No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; No 101046016//Horizon 2020/ ; },
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; Female ; Male ; Middle Aged ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Stress Disorders, Post-Traumatic/epidemiology ; Anxiety/epidemiology ; Depression/epidemiology ; Fatigue ; },
abstract = {BACKGROUND: Post COVID-19 condition (PCC) affects 10-40% of patients and is characterized by persisting symptoms at ≥ 4 weeks after SARS-CoV-2 infection. Symptoms can last 7 or even more months. How long PCC persists and any changes in its clinical phenotypes over time require further investigation. We investigated PCC trajectories and factors associated with PCC persistence.<br><br>MATERIAL AND METHODS: We included both hospitalized COVID-19 patients and outpatients from February 2020 to June 2023, who underwent at least one follow-up visit after acute infection at San Paolo Hospital, University of Milan. Follow-up visits were conducted at the post COVID-19 clinic or via telemedicine. During each follow-up examination, patients completed a short version of the World Health Organization (WHO) Case Report Form (CRF) for ongoing symptoms, the Hospital Anxiety and Depression Scale (HADS), and a screening tool for Post-Traumatic Stress Disorder (PTSD). Statistical analyses involved Chi-square, Mann-Whitney, Kruskal-Wallis tests, and logistic regression analysis.<br><br>RESULTS: We enrolled 853 patients (median age 62, IQR 52-73; 41% females). 551/853 (64.6%), 152/418 (36.4%) and 21/69 (30.4%) presented PCC at median follow up of 3 (IQR 2-3), 7 (IQR 6-10) and 26 (IQR 20-33) months, respectively (p&#x2009;<&#x2009;0.001). The main clinical phenotypes were fatigue, respiratory sequelae, brain fog and chronic pain; anosmia/dysgeusia was observed mostly in the first post-acute period. Female sex, acute disease in 2020, a longer hospital stay and no COVID-19 vaccination were associated with persistence or resolution of PCC compared to never having had PCC. Anxiety, depression and PTSD were more common in PCC patients. By fitting a logistic regression analysis, acute infection in 2020 remained independently associated with persistent PCC, adjusting for age, sex, preexisting comorbidities and disease severity (AOR 0.479 for 2021 vs 2020, 95%CI 0.253-0.908, p&#x2009;=&#x2009;0.024; AOR 0.771 for 2022 vs 2020, 95%CI 0.259-2.297, p&#x2009;=&#x2009;0.641; AOR 0.086 for 2023 vs 2020, 95%CI 0.086-3.830, p&#x2009;=&#x2009;0.565).<br><br>CONCLUSIONS: There was a reduction in the PCC burden 7 months following the acute phase; still, one third of patients experienced long-lasting symptoms. The main clinical presentations of PCC remain fatigue, respiratory symptoms, brain fog, and chronic pain. Having had SARS-CoV-2 infection during the first pandemic phases appears to be associated with persistent PCC.},
}
@article {pmid40301772,
year = {2025},
author = {Kamdem, OL and Dupre, C and Heugno, V and Baudot, A and Essangui, E and Blanquet, M and Guercon, N and Fanget, M and Bayet, S and Vericel, MP and Oustric, P and Mbama Biloa, Y and Shikitele Lola, E and Nekaa, M and Debellis, M and Stierlam, F and Mbia, RF and Tatsilong, O and Assomo Ndemba, P and Ngan, WB and Ndobo, V and Ayina Ayina, C and Mekoulou, J and Ndom Ebongue, MS and Celarier, T and Ruiz, L and Regnier, V and Bika, C and Ngo Sack, F and Ngondi, JL and Barth, N and Mandengue, SH and Roche, F and Botelho-Nevers, E and Eboumbou Moukoko, CE and Nguefeu Nkenfou, C and Hupin, D and Bongue, B and Guyot, J},
title = {SPACO+: a mixed methods protocol to assessing the effectiveness of an educative intervention in patients with Long Covid.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {623},
pmid = {40301772},
issn = {1471-2334},
mesh = {Humans ; *COVID-19/therapy ; Prospective Studies ; Quality of Life ; *Patient Education as Topic/methods ; France ; SARS-CoV-2 ; Cameroon ; Adult ; Female ; Male ; Multicenter Studies as Topic ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; Middle Aged ; Chronic Disease ; },
abstract = {BACKGROUND: The management of many chronic diseases requires a multidisciplinary and holistic approach. Long Covid is a recent, poorly understood disease with several symptoms. Most recommendations suggest a multidisciplinary approach. While there are a few programs aimed to the management of Long Covid, to our knowledge very few were assessed. The SPACO + study therefore aims to evaluate an innovative program which combines the methods used in therapeutic education and in personalized multifactorial intervention for management of Long Covid. Here, we present the protocol of our study, which aims to evaluate the effectiveness of an educational intervention in terms of changes in quality of life at 6 months in comparison with standard clinical practice in patients suffering from Long Covid.<br><br>METHODS: To achieve our objectives, we have planned to carry out a prospective, multicentre, two-arm randomized controlled trial with a convergent parallel mixed methods design. Two countries are involved in this study: France and Cameroon. The study concerns patients aged 18 and over, who have been infected with Covid-19. They must also be diagnosed as having Long Covid in accordance with the WHO definition. The number of subjects required for the study is 400 individuals. Participants will be randomly assigned to either the intervention or control group using a dynamic randomization process to ensure balanced group characteristics. The SPACO&#x2009;+&#x2009;program is an educative intervention with individual follow-up by a nurse dedicated to the program. The SPACO&#x2009;+&#x2009;program offers five workshops, two of which are compulsories. Patients take part in the other workshops according to their needs. The program includes an 8 - 10&#xa0;weeks intervention period. Each session lasts two hours and includes breaks (pacing). The main outcome measure will be quality of life, evaluated through the SF-36. Primary and secondary outcomes, with few exceptions, are assessed before the intervention ("T0"), at 8&#xa0;weeks ("T1" corresponding to the end of SPACO&#x2009;+&#x2009;program's session period) and then 3&#xa0;months later ("T2").<br><br>DISCUSSION: If the SPACO&#x2009;+&#x2009;program is effective and accepted by professionals and patients, it could be disseminated in other regions to assess its transferability. The medico-economic evaluation will also make it possible to assess the benefits provided.<br><br>TRIAL REGISTRATION: This trial is registered under the number NCT05787366 (March 24, 2023). Protocol Version N&#xb0;3.0 (May 31, 2024).},
}
@article {pmid40300093,
year = {2025},
author = {Rane Levendovszky, S and Patel, P and Zhu, C and Rutman, AM and Basha, MM},
title = {Neuroimaging biomarkers of post-acute sequelae of Coronavirus Disease 2019.},
journal = {The British journal of radiology},
volume = {98},
number = {1172},
pages = {1165-1175},
doi = {10.1093/bjr/tqaf090},
pmid = {40300093},
issn = {1748-880X},
support = {R01 HL162743/HL/NHLBI NIH HHS/United States ; //Chronic Post COVID-19 Infection Neuroimaging and Cerebrovascular Imaging/ ; //Bayer Healthcare LLC/ ; //Long terms effects of COVID-19/ ; },
mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biomarkers ; Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging ; },
abstract = {COVID-19, caused by SARS-CoV-2, has led to the condition known as Long COVID or post-acute sequelae of COVID-19 (PASC), where individuals experience persistent debilitating symptoms long after the initial infection. We provide here a comprehensive review of findings in the central nervous system associated with PASC. Neuroimaging has been instrumental in identifying brain changes associated with PASC. Structural MRI studies consistently reveal grey matter volume reductions in the frontal and temporal lobes and white matter hyperintensities, particularly in the periventricular regions. Studies especially found these changes to correlate strongly with cognitive deficits. Diffusion tensor imaging has shown increased tissue damage and oedema in the brain's white matter tracts, particularly in the sagittal stratum and thalamic radiation. Resting-state functional MRI studies indicate altered brain connectivity in PASC patients, especially in those with post-traumatic stress symptoms. Reduced connectivity within and between critical networks, such as the default mode network and the executive control network, has been observed. These changes correlate with cognitive impairments, such as attention and memory deficits. Dynamic functional connectivity analyses further reveal that PASC patients spend less time in states with rich inter-regional connectivity, and transitions between connectivity states were linked to post-traumatic stress disorder symptoms. Positron emission tomography scans have shown hypometabolism in the frontal and temporal lobes, particularly in regions associated with memory and executive functions. Hypometabolism in the hippocampus and thalamus is linked to symptoms like anosmia and fatigue. Despite the heterogeneity in clinical presentations and diagnostic criteria, these neuroimaging findings underscore the significant impact of COVID-19 on brain structure and function. Continued research using advanced imaging techniques is essential for a deeper understanding of PASC's neurological effects. This will aid in developing targeted interventions and improving outcomes for those affected by Long COVID and inform studies investigating downstream effects of viral infections on the brain.},
}
@article {pmid40299883,
year = {2025},
author = {Carpallo-Porcar, B and Jiménez-Sánchez, C and Calvo, S and Irún, P and Kolesnyk-Sumskaya, E and Aller-Blanco, AI and Beamonte, EDC},
title = {ARACOV-02. Specialized nutritional intervention and telerehabilitation in patients with long COVID: Protocol of a randomized controlled trial.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0321811},
pmid = {40299883},
issn = {1932-6203},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/rehabilitation/complications ; *Dietary Supplements ; Double-Blind Method ; Fatty Acids, Omega-3/therapeutic use/administration &amp; dosage ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; *Telerehabilitation ; },
abstract = {BACKGROUND: It is estimated that at least 10% of the population infected with SARS-CoV-2 develop Post COVID Condition, which is characterized by a diverse array of symptoms including dyspnea, fatigue, anxiety, depression, and deterioration in quality of life. The SARS-CoV-2 virus can trigger an excessive immune response, characterized by the release of pro-inflammatory cytokines including IL-6, IL-1, TNFα and reactive oxygen species. Specialized Pro Resolving Mediators (SPMs) (17-HAD, 14-HAD and 18_HEPE) that could be useful in Post COVID Condition modulating the inflammatory response. The objective is to determine the change in quality of life, inflammatory profile, functional capacity and emotional variables in a group taking a nutritional supplement (SPMs) plus a telerehabilitation programme.<br><br>METHODS: ARACOV-2 study is a double-blind, parallel-group, randomized control trial with two parallel interventions: Nutritional supplement and telerehabilitation vs placebo supplement and telerehabilitation. The primary endpoint will be quality of life (EQ-5L-5D). The intervention will last 12 weeks with a daily intake of omega-3 or placebo and a daily supervised rehabilitation programme using telerehabilitation.<br><br>DISCUSSION: This study suggests that SPMs supplementation combined with telerehabilitation may improve inflammation and symptoms like fatigue in Post COVID Condition patients. Both interventions have anti-inflammatory potential, and their combined use could enhance physical and mental health outcomes. This approach offers a promising strategy for managing Post COVID Condition symptoms.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT06063031.},
}
@article {pmid40299849,
year = {2025},
author = {Schaefer, CM and Krause, TM and Delclos, GL and Greenberg, RS},
title = {Risk of post-acute symptoms among adults: A comparison study of severe COVID-19, pneumonia, and influenza.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0322020},
pmid = {40299849},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/complications/pathology ; Male ; Female ; *Influenza, Human/epidemiology/complications/pathology ; Middle Aged ; Adult ; Aged ; Retrospective Studies ; Severity of Illness Index ; *Pneumonia/epidemiology ; SARS-CoV-2/isolation &amp; purification ; United States/epidemiology ; Young Adult ; Risk Factors ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; Comorbidity ; Adolescent ; },
abstract = {BACKGROUND: A retrospective cohort study was undertaken to assess the relationship between initial disease severity of COVID-19 and the risk of post-acute symptoms. The COVID-19 cohort was compared against influenza and pneumonia cohorts to assess whether risk of post-acute symptoms differed.<br><br>METHODS: Administrative health claims data were obtained for commercially insured and Medicare Advantage covered adults (&#x2265; 18 years) with symptomatic laboratory-confirmed COVID-19 diagnosed in 2020 (n=121,205), and similar cohorts of influenza (n=20,844) and pneumonia (n=29,052) patients diagnosed prior to the pandemic. Post-acute symptoms were assessed at four weeks, three and six months following initial diagnosis.<br><br>RESULTS: Among the patients with COVID-19, the likelihood of any post-acute symptom increased with initial disease severity, and was also influenced by the presence of comorbidities, especially rheumatoid arthritis, ischemic heart disease and asthma. The specific post-acute symptoms varied by age, with increased risks of anxiety and headache among the young, whereas the elderly experienced increased brain fog and fatigue. When compared against the influenza and pneumonia cohorts, all three groups experienced post-acute symptoms, with a strong relationship to disease severity, and only partial resolution over the six-month observation period. Those with influenza were less likely than those with COVID-19 to experience post-acute symptoms while those with pneumonia were more likely to have post-acute illness than those with COVID-19.<br><br>CONCLUSIONS: Using a large national dataset, we found that COVID-19 symptomology could not be described by previously seen influenza or pneumonia symptomology and differences exist in the prevalence of symptoms as well as time to resolution, better characterizing "long COVID" and identifying that these differences are unique to COVID-19.},
}
@article {pmid40299550,
year = {2025},
author = {Shariati, M and Gill, KL and Peddle, M and Cao, Y and Xie, F and Han, X and Lei, N and Prowse, R and Shan, D and Fang, L and Huang, V and Ding, A and Wang, PP},
title = {Long COVID and Associated Factors Among Chinese Residents Aged 16 Years and Older in Canada: A Cross-Sectional Online Study.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299550},
issn = {2227-9059},
support = {2223-HQ-000310//Public Health Agency of Canada/ ; },
abstract = {As the COVID-19 pandemic evolved, long COVID emerged as a significant threat to public health, characterized by one or more persistent symptoms impacting organ systems beyond 12 weeks of infection. Informative research has been derived from assessments of long COVID among the Chinese populace. However, none of these studies considered the COVID-19 experience of Chinese residents in Canada. Objectives: We aimed to fill this literature gap by delineating the long COVID experience, prevalence, and associated factors among a sample of Chinese residing in Canada during the pandemic. Methods: The present study employed a cross-sectional online survey questionnaire distributed to a sample of Canadian Chinese using a convenience sampling procedure from 22 December 2022 to 15 February 2023. Respondents were probed for sociodemographic background and health-, COVID-, and vaccine-related characteristics. Logistic LASSO regression was used for model building, and multivariate logistic regression was used to identify factors associated with developing long COVID. Results: Among 491 eligible participants, 63 (12.83%) reported experiencing long COVID with a mean duration of 5.31 (95% CI: 4.06-6.57) months and major symptoms including difficulty concentrating (21.67%), pain/discomfort (15.00%), as well as anxiety/depression (8.33%). Our final model identified significant associations between long COVID and two or more COVID-19 infections (OR = 23.725, 95% CI: 5.098-110.398, p < 0.0001), very severe/severe symptoms (OR = 3.177, 95% CI: 1.160-8.702, p = 0.0246), over-the-counter medicine (OR = 2.473, 95% CI: 1.035-5.909, p = 0.0416), and traditional Chinese medicine (OR = 8.259, 95% CI: 3.016-22.620, p < 0.0001). Further, we identified a significant protective effect of very good/good health status (OR = 0.247, 95% CI: 0.112-0.544, p = 0.0005). Conclusions: Long COVID effected a notable proportion of Canadian Chinese for a prolonged period during the COVID-19 pandemic. Our findings underscore the importance of preexisting health status and reinfection prevention when managing long COVID. Moreover, our work indicates an association between using over-the-counter medicine or traditional Chinese medicine and long COVID experience among Canadian Chinese.},
}
@article {pmid40298722,
year = {2025},
author = {Cavalcanti, CRS and Smaili, SS and Citibaldi, MH and Luis, CV and Arantes, PF and Sígolo, VM and Moura, M and Foguel, D and Chioro, A and Florentino, PTV},
title = {Public perception of the persistence of COVID-19 symptoms and potential strategies to address Long COVID.},
journal = {Ciencia &amp; saude coletiva},
volume = {30},
number = {4},
pages = {e14312024},
doi = {10.1590/1413-81232025304.14312024},
pmid = {40298722},
issn = {1678-4561},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Brazil/epidemiology ; Male ; Female ; Middle Aged ; Adult ; Young Adult ; *Public Opinion ; Adolescent ; Aged ; Post-Acute COVID-19 Syndrome ; *Health Knowledge, Attitudes, Practice ; Interviews as Topic ; },
abstract = {Long COVID is characterized by symptoms that persist for more than 12 weeks after a SARS-CoV-2 infection. This study investigated public perceptions of long COVID in Brazil. Interviews were conducted with 1,295 participants selected based on variable quotas, according to the population distribution in each region of the country, using data from the 2021 National Household Sample Survey (PNAD) and the 2010 IBGE Census. The findings revealed that 40.6% reported having had COVID-19 between 2020 and 2023, with 33.4% experiencing persistent symptoms for at least three months. The most common symptoms included fatigue (44.6%), headache (43.7%), hair loss (40.9%), memory loss (34.7%), and difficulty concentrating (28.7%). The study highlights that Brazilians are unaware of the correlation between these symptoms and the acute phase of the disease. By increasing public awareness of the issue, society becomes more capable of demanding better healthcare services for long COVID and insisting on effective policies. The importance of social education on this topic is fundamental to improving the healthcare system.},
}
@article {pmid40298709,
year = {2025},
author = {Caputo, EL and Feter, N and Delpino, FM and Schröeder, N and Paz, IA and Silva, LSD and Feter, J and Cassuriaga, J and Rocha, JQS and Nascimento, C and Vieira, YP and Rombaldi, AJ and Reichert, FF and Silva, MCD},
title = {What changed after two years of COVID-19: the PAMPA Cohort update profile and methodology.},
journal = {Ciencia &amp; saude coletiva},
volume = {30},
number = {4},
pages = {e06102023},
doi = {10.1590/1413-81232025304.06102023},
pmid = {40298709},
issn = {1678-4561},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Prospective Studies ; Male ; Female ; Adult ; *Mental Health/statistics &amp; numerical data ; Middle Aged ; Brazil/epidemiology ; Exercise ; Anxiety/epidemiology ; Depression/epidemiology ; Health Services Accessibility/statistics &amp; numerical data ; Cohort Studies ; Pandemics ; Low Back Pain/epidemiology ; Aged ; Chronic Disease/epidemiology ; Young Adult ; },
abstract = {The PAMPA Cohort aimed to evaluate the long-term impact of the COVID-19 pandemic on the physical and mental health outcomes of adults. We present data from the fourth wave of the PAMPA Cohort, the updated cohort profile and methodology. The PAMPA Cohort is a prospective study initially designed to have three data collection waves (June 2020, December 2020, and June 2021). With the pandemic progression, three new waves were programmed in addition to the previous waves: 2022. 2023, and 2024. Participants answered about physical activity, mental health, low back pain, healthcare access, and COVID-19, among others. Overall, 2,691 participants answered the wave four. Physical activity levels increased, and symptoms of anxiety and depression were reduced compared to the first assessment. However, a high proportion of chronic diseases was observed, and one-third of participants experienced some degree of food insecurity. Additionally, three-quarters were classified as having long COVID. The indirect effects of the pandemic on both physical and mental health persist in the lives of individuals.},
}
@article {pmid40295670,
year = {2024},
author = {Boese, AS and Warner, BM and McQueen, P and Vendramelli, R and Tailor, N and Griffin, BD and Chan, M and Audet, J and Leung, A and McCorrister, S and Grant, C and Westmacott, G and Kobasa, D},
title = {SARS-CoV-2 infection results in a unique lung proteome long after virus resolution in the hamster.},
journal = {Npj viruses},
volume = {2},
number = {1},
pages = {40},
pmid = {40295670},
issn = {2948-1767},
abstract = {Long COVID or post-acute sequelae of COVID-19 (PASC) remains an ongoing public health issue that causes impairment for those afflicted and diminishes their ability to contribute to society. To address the host response underpinning respiratory PASC, we used the Golden Syrian hamster model infected with ancestral SARS-CoV-2 and examined its lung proteome in a longitudinal experiment. We infected young 6-week old male and female hamsters with 10[5] TCID50 of virus via the intranasal route and sampled the lung at 1, 3, 5, and 31 days post infection (dpi). We compared the infected lung proteome to that of uninfected sex-matched controls. We found almost no differences in protein levels at 1 dpi, with hundreds at 3 dpi, and thousands at 5 dpi. Many overlapping differential protein levels and pathways were seen in both sexes at 3 and 5 dpi including the Coagulation and Complement cascades. Notably, we found differences between the sexes at 31 dpi which included many targets with decreased levels of protein in the males. We also noted an increase in 7 proteins in both sexes at 31 dpi including proteins responsible for airway mucosal layer integrity such as Mucin 5B and Calcium-activated chloride channel regulator 1. Longitudinally, 38 proteins were changed in levels across more than one timepoint in the males but only three proteins were in the females, Secretoglobin family 1 A member 1, Poly [ADP-ribose] polymerase, and Apolipoprotein D. Overall, we show that there are changes to the lung proteome at 31 dpi, a time when no SARS-CoV-2 remains, and that there are sex differences in that proteome after infection with the ancestral strain. We conclude that biological sex should be examined as a variable when testing medical countermeasures for PASC in the Golden Syrian hamster due to host differences between the sexes.},
}
@article {pmid40295119,
year = {2025},
author = {Gotelli, E and Campitiello, R and Pizzorni, C and Sammorì, S and Aitella, E and Ginaldi, L and De Martinis, M and Carubbi, F and Di Ruscio, E and Cuomo, G and Martinelli, E and Marrone, S and De Angelis, R and Giuggioli, D and Guiducci, S and Ingegnoli, F and Riccieri, V and Sebastiani, M and Sulli, A and Smith, V and Cutolo, M and , },
title = {Multicentre retrospective detection of nailfold videocapillaroscopy abnormalities in long covid patients.},
journal = {RMD open},
volume = {11},
number = {2},
pages = {},
pmid = {40295119},
issn = {2056-5933},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Capillaries/pathology/diagnostic imaging ; Case-Control Studies ; *COVID-19/complications/diagnosis ; Italy/epidemiology ; Microcirculation ; *Microscopic Angioscopy/methods ; *Nails/blood supply ; Retrospective Studies ; SARS-CoV-2 ; Scleroderma, Systemic/complications ; },
abstract = {BACKGROUND: SARS-CoV-2 induces acute non-specific endothelial/microvascular alterations that have been identified by nailfold videocapillaroscopy (NVC). Details on NVC abnormalities in long covid (LC) patients (pts) are unknown.<br><br>METHODS: LC pts without and with systemic sclerosis (non-SSc-LC and SSc-LC), recovered COVID-19 (RC) pts that did not develop LC and healthy matched control subjects (CNT) that underwent NVC examinations were evaluated in a multicentre national study from the Capillaroscopy and Microcirculation in Rheumatic Diseases Study Group of the Italian Society of Rheumatology. Retrospective collection was performed for demographic data, course of SARS-CoV-2 infection, comorbidities, concomitant drugs. NVC alterations were quantified by validated scores. Pre-COVID-19 and post-COVID-19 microvascular status was analysed by NVC.<br><br>RESULTS: 62 non-SSc-LC pts (49 female/13 male, 51&#xb1;16 years old), 24 SSc-LC pts (21 female/3 male, 59&#xb1;17 years old), 23 RC pts (18 female/5 male, 51&#xb1;18 years old) and 84 CNT (68 female/16 male, 52&#xb1;12 years old) were analysed. Non-SSc-LC pts showed significantly more dilated capillaries (p<0.01, p multivariate<0.01), microhaemorrhages (p=0.01, p multivariate<0.05), abnormal shapes (p<0.05, p multivariate<0.05) than CNT and of note, lower mean capillary number per linear millimetre (p<0.01, p multivariate<0.01) than both RC pts and CTN (p<0.01, p multivariate<0.05).Of highest interest, 16 non-SSc-LC pts showed statistically significantly more dilated capillaries (p<0.05) and microhaemorrhages (p<0.05) in NVC examinations after COVID-19, compared with pre-COVID-19 status.Similarly, SSc-LC pts (24) showed significantly lower capillary density (p=0.01) and more dilated capillaries (p<0.01) in NVC examinations after COVID-19, compared with pre-COVID-19 status.<br><br>CONCLUSIONS: LC pts show more microvascular alterations at NVC as compared with RC patients and CNT, which may contribute to the pathogenesis of persistent organ/systems dysfunction.},
}
@article {pmid40294910,
year = {2025},
author = {Sessford, JD and Dodwell, A and Elms, K and Gill, M and Premnazeer, M and Scali, O and Roque, M and Cameron, JI},
title = {Factors associated with mental health outcomes among family caregivers to adults with COVID: a scoping review.},
journal = {Disability and rehabilitation},
volume = {47},
number = {23},
pages = {5983-6000},
doi = {10.1080/09638288.2025.2494223},
pmid = {40294910},
issn = {1464-5165},
mesh = {Humans ; *Caregivers/psychology ; *COVID-19/psychology ; *Mental Health ; Adaptation, Psychological ; Adult ; Risk Factors ; SARS-CoV-2 ; Social Support ; },
abstract = {PURPOSE: Family caregivers (FCGs) are essential to the health and wellbeing of people affected by COVID. Protecting mental health of FCGs is essential to sustaining their caregiving role. The objective of this scoping review was to synthesise identified risks factors and protective factors for mental health of FCGs to adults with COVID.<br><br>MATERIALS AND METHODS: Using the Joanna Briggs Institute (JBI) methodology, the search was conducted across Medline, CINAHL, and PsycINFO. Original studies conducted since the pandemic began were included. The population was adult FCGs to adults with COVID, and studies reported mental health outcomes and related factors.<br><br>RESULTS: Of 3474 identified articles, 22 met inclusion criteria (14 quantitative, seven qualitative, one mixed-methods, 18/22 conducted in Iran). Across all study designs, risk factors included limited support, financial burden, family challenges, unpredictable nature of COVID, inexperience, isolation, and unpleasant experiences. Protective factors included accessing support services, self-reinforcement, coping strategies, professional help, and online intervention.<br><br>CONCLUSIONS: Quantitative and qualitative research identified common mental health risk factors and protective factors for FCGs to adults with COVID. These factors may inform development of supports and services for FCGs to people with COVID, such as online interventions. Studies did not distinguish acute versus long COVID.},
}
@article {pmid40294329,
year = {2025},
author = {Karaviti, D and Charakida, M and Dimopoulou, D and Marmarinos, A and Papadaki, M and Maritsi, D and Spyridis, N and Avgeris, M and Gourgiotis, D and Tsolia, M},
title = {Long-term Effects of SARS-CoV-2 Infection on Children's Vasculature.},
journal = {The Pediatric infectious disease journal},
volume = {44},
number = {8},
pages = {792-797},
doi = {10.1097/INF.0000000000004786},
pmid = {40294329},
issn = {1532-0987},
support = {//Evgenides Foundation/ ; },
mesh = {Humans ; *COVID-19/complications/physiopathology/blood ; Child ; Male ; Female ; Carotid Intima-Media Thickness ; Pulse Wave Analysis ; SARS-CoV-2 ; Vascular Stiffness ; Biomarkers/blood ; Adolescent ; C-Reactive Protein ; },
abstract = {BACKGROUND: While long coronavirus disease 2019 (COVID-19) is linked to prolonged vascular dysfunction in adults, research in children remains poor. In this study, we assessed vascular health in children infected with severe acute respiratory syndrome coronavirus 2 about 6.8 months postinfection, comparing them with healthy controls.<br><br>METHODS: Two hundred twenty-three children were assessed and divided into group 1, which included children with a positive disease history and group 2, which consisted of healthy controls. Anthropometric measurements, lipid profile, biomarkers (interleukin-6, C-reactive protein, tumor necrosis factor-alpha and soluble intracellular adhesion molecule) and long COVID symptoms were assessed, along with pulse wave velocity (PWV) measurements and carotid intima-media thickness (cIMT) to evaluate aortic stiffness.<br><br>RESULTS: Children in group 1 were older (mean age: 10.8 &#xb1; 3.2 years vs. 8.5 &#xb1; 2.8 years, P < 0.001) and had higher body mass index (20.3 &#xb1; 5.6&#x2009;kg/m 2 vs. 18.4 &#xb1; 3.5&#x2009;kg/m 2 , P < 0.001). PWV was increased in group 1 (5.02 &#xb1; 0.7 m/s vs. 4.7 &#xb1; 0.6, P < 0.001). However, vascular differences between the groups disappeared after adjusting for age, body mass index, and blood pressure. Soluble intracellular adhesion molecule-1 levels were elevated in children with a history of moderate/severe COVID-19 infection compared with controls (555.8 &#xb1; 113.2&#x2009;ng/mL vs. 428 &#xb1; 42.6&#x2009;ng/mL, P < 0.001). Cholesterol levels, inflammatory markers and cIMT were comparable between groups. Long COVID symptoms were reported mainly by participants of group 1 [34 (23.6%) vs. 3 (3.8%), P < 0.001].<br><br>CONCLUSIONS: This study demonstrates insights into the long-term effects of COVID-19 infection in children. Evidence of endothelial activation without structural arterial changes was found. Persistent inflammation postinfection was absent, yet approximately one-quarter of the participants experienced long COVID symptoms, indicating potential differences in the pathophysiology of postacute COVID-19 infection in childhood.},
}
@article {pmid40293208,
year = {2025},
author = {Almqvist-Ingersoll, P},
title = {Digital Long Covid Communities-Shaping Diagnoses, Treatment Strategies and Modes of Expertise.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70279},
pmid = {40293208},
issn = {1369-7625},
support = {//The project is part of an interdisciplinary project 'Biomedicine, Clinical Knowledge, and the Humanities in Collaboration: A Novel Epistemology for Radically Interdisciplinary Health Research and Policy-Work on Post COVID-19 Syndrome' funded by the Swedish Research Council (Vetenskapsr&#xe5;det, grant number 2021-01245)./ ; },
mesh = {Humans ; *COVID-19/diagnosis/therapy ; *Social Media ; *Patient Participation ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Despite having been created on social media, research into the effects of online engagement on long Covid (LC) as a diagnosis is scarce. Studies on other health-related communities and patient participation argue that social media and other digital technologies have been instrumental in creating new ways for activism, advocacy and sharing of experiences. With its status as patient-made, LC constitutes an example of how diagnoses are (re)constructed through social interactions in addition to Western biomedical science and clinical practice. The aim of the study is to investigate the ways in which lived experiences and larger narratives of LC are communicated and form understandings of the condition as a heterogeneous diagnosis/phenomenon.<br><br>METHODS: This study uses netnography, mainly focused on hidden observations of patient support and advocacy forums in which users' posts are individually sourced and thematically analysed. These themes are further discussed to illustrate overarching discourse that contributes to the sense-making and creation of knowledge surrounding LC.<br><br>RESULTS: The study highlights three major themes, namely: users seeking commonalities in experienced symptoms, interpatient tinkering as a form of biohacking conceptualised as an epistemological process, and negotiating expertise.<br><br>DISCUSSION: The study finds that narratives shared in online spaces regarding LC act as critical factors that serve not just the affected individuals' sense-making and understanding of their lived experience, but also in the construction of the diagnosis itself. Through sharing experiences, symptoms, scientific information and treatment options, forum users contribute to knowledge production processes that change the definition of LC as a diagnosis. Building on the sociology of diagnosis, I argue that LC serves as a significant example of how diagnoses are products of the entanglement between biomedicine, clinical practice, the social and the digital.<br><br>The project operates under the premise that patients from different social, cultural and professional backgrounds participate in online discussions about long Covid and that these individuals work towards individual as well as collective well-being. As such, highlighting their engagement has the potential to inform and strengthen research and clinical practice in various ways.},
}
@article {pmid40291435,
year = {2025},
author = {Hou, C and Xing, Y and Chen, Y and Wang, T and Qi, J and Jia, X and Zeng, X and Bai, J and Lu, W and Deng, Y and Zhong, B and Lei, Y and Chen, Y and Lian, Z and Zhou, H and Yan, J and Yang, X and Yu, H and Zhou, J and Qiu, L and Zhai, Y and Geng, W and Zhong, N and Liu, C and Wang, J},
title = {A Subgroup Reanalysis of the Efficacy of Bufei Huoxue Capsules in Patients With "Long-Covid-19".},
journal = {Pulmonary circulation},
volume = {15},
number = {2},
pages = {e70084},
pmid = {40291435},
issn = {2045-8932},
abstract = {Bufei huoxue capsules (BFHX), manufactured products of traditional Chinese medicine, have demonstrated anti-inflammatory properties and efficacy against chronic pulmonary diseases and COVID-19. This study was designed to further determine the clinical efficacy of BFHX in diverse patient subgroups during the convalescent phase of COVID-19, extending upon previously reported findings from a multicenter randomized controlled trial. Patients who had clinically recovered from COVID-19 were blindly assigned to BFHX or placebo groups. All enrolled patients underwent chest computed tomography (CT) imaging, 6-min walking distance (6MWD) test, and fatigue assessment inventory (FAI) at monthly follow-up for 3 months. A post hoc subgroup reanalysis was performed on subgroups of sex, age, severity of acute illness, and positive/negative IgG antibody against S antigen variants. A total of 129 patients were enrolled in BFHX (N = 64) and placebo groups (N = 65). The 6MWD and FAI scores were more significantly improved in females and mild patients than in males and severe patients after BFHX treatment. Lung CT image evaluated by the change in whole lung volume and mean CT value showed that the patients below 60 years gained more therapeutic effects after 3 months of BFHX treatment (p = 0.0008; p = 0.017; p = 0.0313, respectively). The subgroup reanalysis implies that the therapeutic effectiveness of BFHX in managing COVID-19 convalescence could potentially be influenced by factors including gender, age, and disease severity. Trial registration: This study was registered with the China Clinical Trial Registration Center (registration number: ChiCTR2000032573).},
}
@article {pmid40291369,
year = {2025},
author = {Marchiori, LLM and Marchiori, GM and Okamura, LST and Ciquinato, DSA and Branco, BHM},
title = {An Analysis Between Body Composition and Vertigo Post-Coronavirus Disease 2019 Patients.},
journal = {International archives of otorhinolaryngology},
volume = {29},
number = {2},
pages = {1-8},
pmid = {40291369},
issn = {1809-9777},
abstract = {Introduction An association between the sensation of vertigo, and body composition has not been investigated in post-coronavirus disease 2019 (COVID-19) patients. Objective To evaluate the probable association between the sensation of vertigo and body composition-as amount of fat, bone, and muscle-in post-COVID-19 patients. Methods Cross-sectional study with a sample of post-COVID-19 patients who responded to the visual analog scale (VAS) and the Dizziness Handicap Inventory (DHI). Clinical assessment and electrical bioimpedance were used to determine body composition. Results There were 105 participants evaluated, 61% (n = 64) of whom were male, aged 49.5 ± 11.7 years, with an average height of 165.6 ± 19.9 cm, body weight of 87.6 ± 20 kg, and body mass index (BMI) of 31.1 ± 5.4 kg/m. The prevalence of self-reported vertigo was 51.4% (n = 54); of these, 11.4% (n = 12) related vertigo before the diagnosis of COVID-19, and 40% (n = 42) related vertigo during or after COVID-19. Furthermore, 37.2% (n = 39) of the sample reported that vertigo persisted after medical discharge. In the comparative analysis, the data showed a significant difference between the groups with and without vertigo for height (p = 0.001), body mass (p = 0.006), body water (p = 0.001), lean mass (p = 0.002), fat-free mass (p = 0.001), and musculoskeletal mass (p = 0.001). Conclusion There was a significant association between body composition and the complaint of vertigo in post-COVID-19 patients, suggesting that these aspects should be considered when assessing and can contribute to the construction of knowledge about long COVID.},
}
@article {pmid40291239,
year = {2025},
author = {Sami, CA and Rahaman, MFU and Khan, MMR and Alam Bhuiyan, MM and Matin, MA and Rashed, HM and Khan, AH and Arafat, SM and Hasan, MN},
title = {Glycemic Control Status After Six Months in Post-COVID-19 Patients.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e81225},
pmid = {40291239},
issn = {2168-8184},
abstract = {Background Despite being typically a viral respiratory disease, COVID-19 has harmful effects that go beyond the respiratory system. The endocrine system is particularly susceptible to damage due to the high expression of angiotensin-converting enzyme-2 receptors. This study evaluates glycemic status in survivors of COVID-19. Methodology In this prospective, observational study, 96 individuals were enrolled from the COVID-19 unit of Bangabandhu Sheikh Mujib Medical University (BSMMU). Mild and moderate COVID-19 patients were classified as non-severe, whereas severe and critical cases were classified as severe, following the WHO disease severity classification. Follow-ups were conducted at the post-COVID-19 clinic at BSMMU one and six months after diagnosis. Blood samples for fasting blood sugar and glycated hemoglobin measurements were collected within 24 hours of initial diagnosis and during each follow-up at the first and sixth months. Results Of the 96 participants, the non-severe and severe groups consisted of 49 (51%) and 47 (49%) participants, respectively. Among the participants, 62 (63.9%) were men, the mean age was 54.2 (15.9) years, and hypertension was the most common comorbidity (37, 38.5%). After six months, 12 new cases of diabetes (15.4%) were observed, with a male predominance (10, 62%). After adjusting for potential confounders, we found that severe COVID-19 was substantially linked to a higher risk of diabetes at six months (odds ratio = 5.5, 95% confidence interval, 1.1-27.7, p = 0.03). Conclusions The study findings showed a significant association between a higher frequency of diabetes and severe COVID-19.},
}
@article {pmid40287611,
year = {2025},
author = {Choi, YJ and Lee, JS and Joung, JY and Hwang, SJ and Kim, YY and Son, CG},
title = {Mitigating fatigue in long COVID patients with MYP[plus]: a clinical observation.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {611},
pmid = {40287611},
issn = {1471-2334},
mesh = {Humans ; *Fatigue/drug therapy/etiology ; Male ; Female ; *COVID-19/complications ; Middle Aged ; Adult ; Quality of Life ; SARS-CoV-2 ; Aged ; Cytokines/blood ; *Plant Extracts/therapeutic use ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE: The COVID-19 pandemic has led to the emergence of a secondary public health crisis known as Long COVID. It is estimated that approximately 10% of individuals who contact COVID-19 develop Long COVID, with fatigue and brain fog being among the most commonly reported and debilitating symptoms. However, no standardized or effective treatments are currently available. This observational study aimed to evaluate the efficacy of MYP[plus], an herbal formulation composed of Astragali Radix, Salviae Radix, and Aquilariae Lignum, in alleviating fatigue and brain fog in patients with Long COVID.<br><br>METHODS: Subjects with a score of 60 or higher on the Modified Korean version of the Chalder Fatigue scale (mKCFQ11) or a brain fog rating of 5 or higher on the visual analogue scale (VAS) took two capsules of MYP[plus] (500&#xa0;mg per capsule) twice daily for 4 weeks. Changes in symptoms were assessed using the mKCFQ11, Multidimensional Fatigue Inventory (MFI-20), Fatigue VAS, Brain fog VAS, and overall quality of life using the Short-Form Health Survey (SF-12). Additionally, levels of three cytokines (TNF-&#x3b1;, TGF-&#x3b2;, IFN- &#x3b3;) and cortisol were measured.<br><br>RESULTS: Fifty participants successfully completed the 4-week administration with MYP[plus]. At baseline, fatigue severity was 75.3&#x2009;&#xb1;&#x2009;10.9 in mKCFQ11, 70.9&#x2009;&#xb1;&#x2009;11.2 in MFI-20, 7.5&#x2009;&#xb1;&#x2009;1.2 in Fatigue VAS, 8.4&#x2009;&#xb1;&#x2009;1.1 in Brain fog VAS, and 45.3&#x2009;&#xb1;&#x2009;17.8 in SF-12. All parameters significantly improved (p&#x2009;<&#x2009;0.01), with a decrease of 46% in mKCFQ11, 26% in MFI-20, 49% in Fatigue VAS, and 52% in Brain fog VAS, and an increase of 59% in SF-12, respectively. Unlikely others, the plasma level of TGF-&#x3b2; showed a declining pattern after MYP[plus] administration (from 765.0&#x2009;&#xb1;&#x2009;1759.7 to 243.9&#x2009;&#xb1;&#x2009;708.1 pg/mL, p&#x2009;=&#x2009;0.07). No safety concerns were observed.<br><br>CONCLUSION: This pilot observational study suggests the clinical potential of MYP[plus] for managing patients with Long COVID, focusing on fatigue-related symptoms and quality of life. Further studies are required to confirm its efficacy and safety using large-scale randomized placebo-controlled trials in the future.<br><br>PROTOCOL REGISTRATION: This study has been retrospectively registered with the identifier number KCT0008948 on https://cris.nih.go.kr , as of 27/10/23.},
}
@article {pmid40287369,
year = {2025},
author = {Lue, W and Kaifang, D},
title = {Comment on "Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from Taiwan".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2025.04.029},
pmid = {40287369},
issn = {0929-6646},
}
@article {pmid40287027,
year = {2025},
author = {Renner, K and Stauffenberg, F and Paulus, M and Neumayer, S and Winter-Köhler, F and Buchtler, S and Schmalenberger, D and Blaas, S and Mohr, A and Pfeifer, M and Malfertheiner, MV and Loew, T and Sester, M and Bals, R and Peterhoff, D and Schmidt, B and Mack, M},
title = {Hyper-reactivity of CD8[+] T cells and high expression of IL-3 correlates with occurrence and severity of Long-COVID.},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {277},
number = {},
pages = {110502},
doi = {10.1016/j.clim.2025.110502},
pmid = {40287027},
issn = {1521-7035},
mesh = {Humans ; *CD8-Positive T-Lymphocytes/immunology ; *COVID-19/immunology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Adult ; Aged ; *Interleukin-3/immunology/metabolism ; Lymphocyte Activation/immunology ; Interleukin-2 Receptor alpha Subunit/immunology/metabolism ; Severity of Illness Index ; Interferon-gamma/immunology ; Interleukin-2/immunology ; },
abstract = {Following SARS-CoV-2 infection, some individuals develop Long-COVID-syndrome lasting for more than 3 months. We analyzed blood samples from patients with Long-COVID, controls without persistent symptoms following SARS-CoV-2-infection and non-infected donors without a history of infection. Long-COVID patients showed clear signs of T cell hyper-activation predominantly in the CD8[+] T cell subset with a 4-fold higher expression of CD25 and 2-fold more effector-memory T cells. Following polyclonal T cell stimulation, we found a 2-fold stronger upregulation of CD25 and a 7-fold higher release of IL-3 in Long-COVID. Intracellular staining revealed 5-fold more IL-3-expressing CD8[+] T cells in Long-COVID, while GM-CSF, IFN-γ and IL-2 were much less upregulated. These changes correlated with the severity of Long-COVID and persisted for up to 18 months after infection. Our data reveal a pronounced and long-lasting CD8[+] T cell hyper-activation and hyper-reactivity in Long-COVID and speak for a trial of T cell-immunosuppression in patients with Long-COVID.},
}
@article {pmid40284540,
year = {2025},
author = {Jason, LA and Katz, BZ},
title = {Predisposing and Precipitating Factors in Epstein-Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {Microorganisms},
volume = {13},
number = {4},
pages = {},
pmid = {40284540},
issn = {2076-2607},
abstract = {Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are two examples of post-viral syndromes. The identification of risk factors predisposing patients to developing and maintaining post-infectious syndromes may help uncover their underlying mechanisms. The majority of patients with ME/CFS report infectious illnesses before the onset of ME/CFS, with 30% of cases of ME/CFS due to IM caused by the Epstein-Barr virus. After developing IM, one study found 11% of adults had ME/CFS at 6 months and 9% had ME/CFS at 1 year. Another study of adolescents found 13% and 7% with ME/CFS at 6 and 12 months following IM, respectively. However, it is unclear which variables are potential risk factors contributing to the development and maintenance of ME/CFS following IM, because few prospective studies have collected baseline data before the onset of the triggering illness. The current article provides an overview of a study that included pre-illness predictors of ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. Our data set included an ethnically and sociodemographically diverse group of young adult students, and we were able to longitudinally follow these youths over time to better understand the risk factors associated with the pathophysiology of ME/CFS. General screens of health and psychological well-being, as well as blood samples, were obtained at three stages of the study (Stage 1-Baseline-when the students were well, at least 6 weeks before the student developed IM; Stage 2-within 6 weeks following the diagnosis of IM, and Stage 3-six months after IM, when they had either developed ME/CFS or recovered). We focused on the risk factors for new cases of ME/CFS following IM and found factors both at baseline (Stage 1) and at the time of IM (Stage 2) that predicted nonrecovery. We are now collecting seven-year follow-up data on this sample, as well as including cases of long COVID. The lessons learned in this prospective study are reviewed.},
}
@article {pmid40283075,
year = {2025},
author = {Loboda, D and Golba, KS and Gurowiec, P and Bredelytė, A and Razbadauskas, A and Sarecka-Hujar, B},
title = {Variability in Arterial Stiffness and Vascular Endothelial Function After COVID-19 During 1.5 Years of Follow-Up-Systematic Review and Meta-Analysis.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40283075},
issn = {2075-1729},
support = {BNW-2-016/N/4/K//Medical University of Silesia/ ; },
abstract = {Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30-90 days), mid-term (>90-180 days), late (>180-270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= -2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= -0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient's initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement.},
}
@article {pmid40282054,
year = {2025},
author = {Xu, SS and Li, Y and Li, W and Capio, CM and Tso, WWY and Chan, DKC},
title = {The Impact of Long COVID on Language Proficiency Across Different School Levels in Hong Kong.},
journal = {Behavioral sciences (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40282054},
issn = {2076-328X},
support = {"Long-COVID: Prevalence and Impact on Hong Kong children" (#04753)//the Vice President (Research and Development) Office at The Education University of Hong Kong/ ; },
abstract = {Long COVID, where symptoms persist after recovering from COVID-19, can affect cognitive functions like language. However, little is known about its impact on children's language skills, especially across d