@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.

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

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

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

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

@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.

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

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

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

@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 & 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 & 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.

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

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

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

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

@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 & control ; *Health Promotion/methods ; *COVID-19 Vaccines/administration & 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.

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

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

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

Humans
*COVID-19/prevention & control
*Health Promotion/methods
*COVID-19 Vaccines/administration & dosage
*Health Equity
Colorado
*Information Dissemination/methods

@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.

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

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

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

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

@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.

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

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

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

@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 & 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.

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

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

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

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

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 & numerical data
Aged
Surveys and Questionnaires

@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 & 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.

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

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

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

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

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

Humans
*COVID-19/complications/physiopathology/therapy
*Dyspnea/therapy/physiopathology
Male
Female
Post-Acute COVID-19 Syndrome
Middle Aged
*Spirometry/methods
SARS-CoV-2/isolation & purification
Quality of Life
Functional Status
Aged
Taiwan
Adult
*Breathing Exercises/methods

@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.

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

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

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

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

@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.

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

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

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

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

@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.

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

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

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

@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 & control/complications ; Child, Preschool ; Adolescent ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Infant ; SARS-CoV-2/isolation & 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.

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

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

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

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

Humans
Child
Female
Male
Retrospective Studies
*COVID-19/prevention & control/complications
Child, Preschool
Adolescent
*COVID-19 Drug Treatment
Post-Acute COVID-19 Syndrome
Infant
SARS-CoV-2/isolation & purification
*Steroids/therapeutic use
Cohort Studies
Electronic Health Records
Acute Disease

@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 & 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.

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

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

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

@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.

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

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

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

@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.

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

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

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

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

@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 & 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.

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

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

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

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

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 & purification
Adult
Aged
Fatigue
Surveys and Questionnaires

@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 & 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.

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

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

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

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

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 & purification
Aged
Surveys and Questionnaires

@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, & 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 & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70165},
pmid = {42300213},
issn = {1934-1563},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; COFECUB88887.188974/2025-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 00193.00000773/2021-72//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193.00001222/2021-26//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193-00001261/2021-23//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193-00002357/2022-90//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193-00001623/2024-29//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 308519/2025-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 402816/2023-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 141130/2023-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 131422/2023-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
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.

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

DESIGN: Longitudinal observational study.

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

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

INTERVENTIONS: Not applicable.

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

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

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

TRIAL REGISTRATION: NCT04961255.},
}

@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.

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

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

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

@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.},
}

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

@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.},
}

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

@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 & 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.

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

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

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

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 & purification
Aged
Risk Factors

@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.

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

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

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

@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.

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

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

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

@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.

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

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

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

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

@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 & control/epidemiology ; Retrospective Studies ; Middle Aged ; *COVID-19 Vaccines/administration & dosage/immunology ; SARS-CoV-2/immunology ; *Vaccine Efficacy ; Seasons ; Vaccination/statistics & 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.

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

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

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

Humans
Germany/epidemiology
Female
Male
Aged
*COVID-19/prevention & control/epidemiology
Retrospective Studies
Middle Aged
*COVID-19 Vaccines/administration & dosage/immunology
SARS-CoV-2/immunology
*Vaccine Efficacy
Seasons
Vaccination/statistics & numerical data
Aged, 80 and over
Cohort Studies

@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.

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

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

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

@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.

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

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

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

@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.

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

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

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

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

@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.

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

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

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

@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.

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

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

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

@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 & 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‑12‑04‑001‑2022//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.},
}

Humans
*COVID-19/immunology/blood
*Cytokines/blood
Longitudinal Studies
Female
Male
Middle Aged
Post-Acute COVID-19 Syndrome
SARS-CoV-2/immunology
Aged

@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.

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.

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.

TRIAL REGISTRATION: ClinicalTrials.gov - Platform: NCT06404047 ; Appendix A: NCT06404060 ; Appendix B: NCT06404073 . Registered on May 6, 2024.

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.

METHODS: Retrospective cohort study of adults (≥18 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.

RESULTS: Of 1610 patients, 39.1% were ethnic minority patients. Ethnic minorities were younger, had longer symptom duration (7 vs 6 days, p < 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).

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.

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.

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 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.

CONCLUSION: Participants with COVID-19 had higher odds of all outcomes, especially within the first 4 weeks. After 12 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 & 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.

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 ≥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 ≥84 days post-infection. After propensity score (PS) fine stratification, hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression.

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).

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.

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.

STUDY DESIGN: A scoping review.

SETTING: Outpatient clinics where patients received sympathetic blocks or parasympathetic blocks.

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.

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.

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.

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 & 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.

METHODS: Patients (n = 392) were randomized 1:1 to receive BA or placebo every 5 days for 71 days. Percent predicted forced vital capacity (ppFVC), respiratory symptoms, and exercise tolerance indicators were assessed at baseline and on Days 71 (Δ ppFVC was the primary endpoint) and 180.

RESULTS: The pre-specified primary endpoint (Δ ppFVC at Day 71) was negative (+0.30%, p = 0.817). Secondary endpoints showed reduced exertional desaturation (OR 0.36, p = 0.006) and dyspnea (OR 0.62, p = 0.040).

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.

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.

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.

RESULTS: Final sample size was 1,285. Compared to the participants with no long COVID, the HRQoL among long COVID patients (β: -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 (β: -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 (β: -0.47; 95% CI: -0.57 to -0.36; AME: -0.065), class 2 (β: -0.48; 95% CI: -0.60 to -0.35; AME: -0.066), and class 3 (β: -0.93; 95% CI: -1.06 to -0.79; AME: -0.148) had poorer HRQoL.

CONCLUSIONS: Long COVID patients had reduced HRQoL. Female gender, young-age, thin BMI or pre-existing psychological disorders were associated with lower HRQoL.},
}

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

@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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 & 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.

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-1ß, PTX3, TNF-a, VCAM-1, ICAM-1 and E-Selectin. Associations between each biomarker level and eGFR were analyzed.

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.

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.

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.

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."

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.

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.

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.

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.

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 < 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.

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.

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.

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 days post-infection.

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 SGLT2i had a significantly lower risk of neurological sequelae (aHR = 0.60 [0.45-0.81]), particularly memory and cognitive impairment (aHR = 0.63 [0.41-0.98]). SGLT2i was also associated with a reduced risk of post-acute symptoms (aHR = 0.87 [0.77-0.99]). Metformin use was associated with significantly lower risk of composite post-acute outcomes (aHR = 0.80 [0.68-0.96]) and post-acute symptoms (aHR = 0.77 [0.63-0.93]). Amongst patients on metformin, the addition of SGLT2i further lowered the risk of neurological sequelae (aHR = 0.81 [0.71-0.93]) and composite symptoms (aHR 0.87 [0.76-0.99]).

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.

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.

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 (β = 0.06, P < 0.001) and pre-existing psychiatric disorders (β = 0.37, P < 0.001) were significantly associated with higher CGI-S scores over time; among psychological sub-factors, cognitive-physical exhaustion (β = 0.28, P < 0.001), emotional distress (β = 0.32, P < 0.001), and self-destructive coping (β = 0.12, P < 0.001) were significant predictors, with emotional distress significant in men (β = 0.26, P = 0.001) and both cognitive-physical exhaustion (β = 0.36, P < 0.001) and emotional distress (β = 0.36, P < 0.001) significant in women.

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.

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.

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.

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.

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 ≥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.

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.

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.

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 ≥30 years with confirmed SARS-CoV-2 infection and ≥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.

RESULTS: The median age was 47 years (interquartile range 38-57); 63% were female; 47% Hispanic/Latino; 83% reported ≥1 prior COVID-19 infections or ≥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).

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.

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.

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 ≥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.

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.

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 ≥ 1 long COVID signs/symptoms or long COVID diagnostic or referral code ≥ 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.

RESULTS: Of 5,661 eligible patients, 2,772 (49.0%) had long COVID; of these, very few (0.8%; n = 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 £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.

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.

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.

RESULTS: Fatigue was significantly and strongly associated with all other symptoms (p < 0.001), poor sleep quality (p < 0.001), psychological traits and negative emotions (p < 0.001), and lower quality of life (p < 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.

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.

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.

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.

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.

OBJECTIVE: To analyze associations between inspiratory muscle fatigue, pulmonary radiopharmaceutical activity, and sleep disturbances in symptomatic and asymptomatic post-COVID-19 individuals.

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]ᵐTc-DTPA and [99]ᵐTc-MAA, respectively; total radiopharmaceutical activity was quantified for both lungs combined and for the right and left lungs separately.

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).

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 & numerical data ; Male ; Prospective Studies ; Middle Aged ; Socioeconomic Disparities in Health ; *Healthcare Disparities/statistics & 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.

METHODS: We analysed responses to both closed (N = 3516) and open (N = 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.

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.

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.},
}

Humans
United Kingdom/epidemiology
*COVID-19/epidemiology/therapy
Female
*Health Services Accessibility/statistics & numerical data
Male
Prospective Studies
Middle Aged
Socioeconomic Disparities in Health
*Healthcare Disparities/statistics & numerical data
Adult
Socioeconomic Factors
Aged
SARS-CoV-2
Surveys and Questionnaires
Access to Primary Care

@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 & 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).

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.

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 months postenrollment or 2 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 data.

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 - encompassing neurocognitive function, physical symptoms, quality of life, and work status - 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.

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.

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.

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.

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.},
}

Humans
*Cognitive Dysfunction/epidemiology/etiology
Prevalence
*COVID-19/complications/epidemiology
Post-Acute COVID-19 Syndrome
Female
Male
SARS-CoV-2