@article {pmid41351342,
year = {2025},
author = {Winkel, AMAM and de Jonghe, BA and Lap, CR and Haverkort, ME and Sluiter-Post, JGC and Euser, SM and Eggink, D and Geerlings, SE and Tami, A and de Jong, MD and van Lelyveld, SFL and van Houten, MA},
title = {Persistent Symptoms in SARS-CoV-2-Infected and Non-Infected Household Members: A Prospective Cohort Study.},
journal = {Journal of medical virology},
volume = {97},
number = {12},
pages = {e70727},
doi = {10.1002/jmv.70727},
pmid = {41351342},
issn = {1096-9071},
support = {//The SARSLIVA 1 study was supported by internal funds from the National Institute for Public Health and the Environment (RIVM), and by the Netherlands Organisation for Health Research and Development (ZonMw), grant number 10430012010017, financed in part by the Netherlands Ministry of Health, Welfare and Sport./ ; },
mesh = {Humans ; *COVID-19/epidemiology/psychology/diagnosis ; Adult ; Prospective Studies ; Male ; Female ; Middle Aged ; Quality of Life ; Child ; Adolescent ; *SARS-CoV-2/isolation & purification ; Young Adult ; Anxiety/epidemiology ; Netherlands/epidemiology ; Depression/epidemiology ; Family Characteristics ; Prevalence ; Fatigue/epidemiology ; Surveys and Questionnaires ; Saliva/virology ; },
abstract = {This prospective study assessed the prevalence, type, and consequences of persistent symptoms following a nonhospitalized SARS-CoV-2 infection by comparing infected and noninfected children and adults of Dutch households. Two comparable prospective household studies were conducted during two pandemic phases. At baseline, all household members were tested for SARS-CoV-2 with 10 consecutive saliva samples during a 6-week period using RT-PCR. Questionnaires assessing persistent symptoms, health-related quality of life (HRQoL), anxiety, and depressive symptoms were collected at 6 and 12 months. Of the 297 included participants (median age 34 years, IQR 12-48), 201 (67.7%) tested positive for SARS-CoV-2. At 6 months, only one child reported persistent symptoms. SARS-CoV-2-infected adults (> 18 years) reported more pulmonary symptoms (15.2% vs. 3.4%, p = 0.023), and tended to report more fatigue (12.8% vs. 3.4%, p = 0.061) and exertion-related symptoms (8.8% vs. 1.7%, p = 0.107) compared to the negative adults. Adult participants with persistent symptoms reported decreased HRQoL and increased anxiety and depressive symptoms. This study found that SARS-CoV-2-positive adults tended to have higher prevalence of respiratory symptoms, fatigue, and exertion-related symptoms 6 months after SARS-CoV-2 infection, whereas children rarely reported persistent symptoms. Persistent symptoms were associated with a reduced HRQoL and increased anxiety and depression.},
}

Humans
*COVID-19/epidemiology/psychology/diagnosis
Adult
Prospective Studies
Male
Female
Middle Aged
Quality of Life
Child
Adolescent
*SARS-CoV-2/isolation & purification
Young Adult
Anxiety/epidemiology
Netherlands/epidemiology
Depression/epidemiology
Family Characteristics
Prevalence
Fatigue/epidemiology
Surveys and Questionnaires
Saliva/virology

@article {pmid41350176,
year = {2025},
author = {Miller, CM and Moen, JK and Iwasaki, A},
title = {The lingering shadow of epidemics: post-acute sequelae across history.},
journal = {Trends in immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.it.2025.10.010},
pmid = {41350176},
issn = {1471-4981},
abstract = {The SARS-CoV-2 pandemic has drawn global attention to post-acute infection syndromes (PAIS), with millions affected by post-acute sequelae of COVID-19 (PASC, or Long COVID). While Long COVID is newly defined, PAIS have been described for over a century following epidemic infections. Multiple pathogens - including influenza, Epstein-Barr virus, and Borrelia burgdorferi, among others - can precipitate persistent, poorly understood symptoms. Chronic illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long been linked to infectious triggers. This recurring association highlights critical knowledge gaps and underscores the need for systematic investigation. Unlike prior pandemics, the current era offers advanced technologies and analytic tools to address these gaps. Defining the biology of Long COVID may yield broader insights into host-pathogen interactions and mechanisms of chronic illness.},
}

@article {pmid41349462,
year = {2025},
author = {Eksteen, C and Asja, LC and Rass, A and Riedemann, J and Engelbrecht, AM},
title = {Post COVID-19 pandemic Inflammatory Insights into Cancer: Consequences for immunotherapy.},
journal = {Cytokine & growth factor reviews},
volume = {87},
number = {},
pages = {10-18},
doi = {10.1016/j.cytogfr.2025.12.002},
pmid = {41349462},
issn = {1879-0305},
abstract = {The COVID-19 pandemic has reshaped the landscape of global health, revealing novel interactions between infectious diseases and chronic conditions such as cancer. Beyond acute infection, growing evidence suggests that persistent exposure to SARS-CoV-2 spike protein, whether through infection or vaccination, may sustain inflammatory pathways that contribute to tumour progression and immune modulation. This review explores the overlap between post-COVID inflammation, particularly in Long-COVID syndromes and the tumour microenvironment (TME), focusing on key mediators such as IL-6, TNF-α, IL-1β, and NF-κB. We revisit the concept of the cytokine storm in the context of persistent inflammation, spike protein immunogenicity and immune exhaustion, proposing a model in which chronic inflammatory signalling may disrupt tumour immune surveillance, reawaken dormant cancer cells and compromise the efficacy of immunotherapies. Comparative analysis with other cancer types highlights shared pathways of oncogenic inflammation. Lastly, we outline emerging therapeutic strategies to mitigate these effects, including cytokine-targeted interventions and immunomodulatory screening in post-COVID cancer patients. These post-pandemic insights call for urgent translational research to ensure effective and safe cancer immunotherapy in the evolving inflammatory landscape.},
}

@article {pmid41349247,
year = {2025},
author = {Halma, M and Varon, J},
title = {Metabolic modulation as a therapeutic strategy for post-acute vaccination syndrome (PACVS): A review of pathomechanisms and existing therapeutic components.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {193},
number = {},
pages = {118864},
doi = {10.1016/j.biopha.2025.118864},
pmid = {41349247},
issn = {1950-6007},
abstract = {Post-Acute Vaccination Syndrome (PACVS) is a post-vaccination disorder marked by persistent fatigue, cognitive impairment, and exercise intolerance. Current research identifies interconnected pathophysiological processes, including persisting spike protein, mitochondrial dysfunction, decreased tissue oxygenation, and impaired metabolism. Emerging treatments rely on metabolic regulation and therapeutic agents promoting mitochondrial and vascular function. These therapies stimulate cellular energy generation, reduce oxidative stress, and regulate inflammatory pathways. This review examines metabolic and mitochondrial mechanisms underlying PACVS, evaluates existing therapeutic strategies targeting these pathways, and synthesizes current evidence for future research and clinical management.},
}

@article {pmid41348962,
year = {2025},
author = {Carrouel, F and Lvovschi, VE and du Sartz de Vigneulles, B and Rhanoui, M and Salamon, R and Lamure, M and Salque, C and Lan, R and Dussart, C},
title = {Prevalence, Risk Factors, Disease-Related Knowledge, and Vaccination Attitudes and Behaviors for Long COVID Among French Civil Servants: Cross-Sectional Survey.},
journal = {JMIR public health and surveillance},
volume = {11},
number = {},
pages = {e83323},
doi = {10.2196/83323},
pmid = {41348962},
issn = {2369-2960},
mesh = {Humans ; Cross-Sectional Studies ; France/epidemiology ; *COVID-19/epidemiology/prevention & control/psychology ; Male ; Female ; *Health Knowledge, Attitudes, Practice ; Middle Aged ; Adult ; Risk Factors ; Prevalence ; *COVID-19 Vaccines/administration & dosage ; Surveys and Questionnaires ; *Government Employees/statistics & numerical data/psychology ; *Vaccination/statistics & numerical data/psychology ; Aged ; },
abstract = {BACKGROUND: Long COVID affects millions worldwide, straining health systems and workforce stability. This first nationwide survey among French civil servants combines epidemiological assessment with a Knowledge, Attitudes, and Behaviors approach. Long COVID remains a diagnostic and epidemiological challenge with evolving symptoms and uncertain categorization, particularly among self-suspected cases. Beyond prevalence and risk factors, understanding behavioral dimensions is essential to developing prevention strategies and maintaining workforce resilience.

OBJECTIVE: This study aimed to (1) assess the prevalence of long COVID among French civil servants; (2) identify associated sociodemographic, occupational, and health-related factors; (3) assess disease-related knowledge of long COVID and (4) examine attitudes and behaviors regarding COVID-19 vaccination.

METHODS: This cross-sectional survey was conducted in 2024 among active or retired civil servants in France. A Knowledge, Attitudes, and Behaviors-validated questionnaire, based on World Health Organization guidelines, was used. Responses were compared across 4 COVID-19 status groups (no COVID, COVID-19 without long COVID, diagnosed long COVID, and suspected long COVID). Statistical analyses included univariate tests and multivariable logistic regressions to identify factors associated with diagnosed or suspected long COVID.

RESULTS: Among 3962 eligible respondents, 61 (1.54%; 95% CI 1.20-1.97) reported a formal diagnosis of long COVID and 241 (6.08%; 95% CI 5.38-6.87) without diagnosis. Diagnosed long COVID was significantly associated with long-term sick leave (odds ratio [OR] 1.15, 95% CI 1.03-6.28; P=.04) and long-term illness coverage (OR 0.72, 95% CI 0.27-0.92; P=.03). Suspected long COVID was associated with being in a relationship (OR 1.65, 95% CI 1.08-2.52; P=.02), widowed (OR 2.25, 95% CI 1.18-4.31; P=.01), and uncertain (OR 1.90, 95% CI 1.32-2.74; P<.001) or incomplete COVID-19 vaccination status (OR 1.67, 95% CI 1.16-2.42; P=.01). Knowledge scores differed significantly across groups (ANOVA F3,3476=24.31, P<.001; χ²6=54.92, P<.001), with diagnosed cases showing the highest proportion of high knowledge (13/61, 21%) compared to 12.4% in the non-COVID group. Among 61 diagnosed cases, 36 (59%; 95% CI 46.4-70.5) were vaccinated, 13 (21%; 95% CI 12.9-33.2) intended to get vaccinated, and 12 (20%; 95% CI 11.6-31.3) remained unvaccinated; among suspected cases, these proportions were 173 (71.8%; 95% CI 65.9-77.1), 30 (12.4%; 95% CI 8.8-17.3), and 38 (15.8%; 95% CI 11.6-21.0), respectively.

CONCLUSIONS: Unlike previous studies that examined the clinical or behavioral factors separately, this nationwide analysis linked epidemiological data with knowledge and vaccination behaviors. Among French civil servants, long COVID remains underdiagnosed, where absenteeism and sick leave threaten essential services. The study highlights disparities in disease-related knowledge, vaccination attitudes, and behaviors, underlining the importance of workplace health education and systematic screening. Vaccination is associated with lower odds of long COVID, reinforcing its preventive value. Thus, findings reveal organizational implications and support workplace-based prevention strategies integrating vaccination promotion, early detection, and health literacy to sustain the resilience of public services.},
}

Humans
Cross-Sectional Studies
France/epidemiology
*COVID-19/epidemiology/prevention & control/psychology
Male
Female
*Health Knowledge, Attitudes, Practice
Middle Aged
Adult
Risk Factors
Prevalence
*COVID-19 Vaccines/administration & dosage
Surveys and Questionnaires
*Government Employees/statistics & numerical data/psychology
*Vaccination/statistics & numerical data/psychology
Aged

@article {pmid41347787,
year = {2025},
author = {Ahmetaj-Shala, B and Peacock, TP and Baillon, L and Swann, OC and Gashaw, H and Rustagi, A and Barclay, WS and Mitchell, JA},
title = {Resistance of endothelial cells to SARS-CoV-2 infection in vitro.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0120525},
doi = {10.1128/jvi.01205-25},
pmid = {41347787},
issn = {1098-5514},
abstract = {The secondary thrombotic/vascular clinical syndrome of COVID-19 suggests that SARS-CoV-2 infects the endothelium; however, robust in vitro infection of endothelial cells by various strains of SARS-CoV-2 remains to be demonstrated and continues to be debated. Here, we revisit the question of endothelial cell permissiveness to SARS-CoV-2 using isolated endothelial cells (from the lung, aorta, and endothelial cell progenitors), and additionally, to overcome limitations associated with cultured cells, using native endothelial cells within living precision cut human lung slices and single-cell RNA sequencing to track viral presence. Cellular infection in endothelial monocultures was determined using fluorescence imaging. Mediator release was measured by ELISA, and gene expression was assessed by RT-qPCR. Infection in lung slices was determined using single-cell RNA sequencing, capturing molecular identifiers that aligned to the SARS-CoV-2 viral genome (for lung slices). Each cultured endothelial cell type displayed functional viral responses by increased release of IP-10 when stimulated with Poly-IC (TLR3) or Imiquimod (TLR7/8). Compared to nasal epithelial cells, endothelial cells expressed low or undetectable levels of ACE2 and showed susceptibility to Ebola and Vesicular Stomatitis Virus glycoprotein-expressing pseudoviruses but not live SARS-CoV-2. Importantly, native endothelial cells within human lung slices displayed minimal infectability with SARS-CoV-2. To our knowledge, this is the first study to demonstrate that neither cultured nor native human endothelial cells are particularly, directly permissive to SARS-CoV-2, likely due to the lack of sufficient AEC2 expression. These observations confirm that the vascular inflammation and cardiovascular consequences of COVID-19 are largely an indirect result of paracrine inflammatory responses.IMPORTANCESARS-CoV-2 is recognized not only for its acute effects and links with cardiovascular events but also for its ability to cause long COVID syndrome, which is now a major concern particularly since its long-term implications remain poorly understood. Revisiting endothelial cell permissivity to SARS-CoV-2 is therefore critical in this setting. We show that SARS-CoV-2, and several strains, do not infect cultured different types of endothelial cells cultured alone or native endothelial cells in situ in human lung tissue. Our findings are in line with the idea that vascular inflammation and thrombosis seen in COVID-19 are independent of direct endothelial cell infection and likely to be mediated by factors released by adjacent infected cells or circulating systemic inflammatory mediators. Our work also suggests that where viremia occurs, SARS-CoV-2 passes through the endothelium, facilitated by loss of barrier function because of local inflammation at the site of infection.},
}

@article {pmid41347697,
year = {2025},
author = {Kaptain, RJ and Jensen, KEB and Nielsen, KT and Wæhrens, EE},
title = {Activities of daily living following Long COVID: An exploratory cross-sectional study.},
journal = {Scandinavian journal of occupational therapy},
volume = {32},
number = {1},
pages = {2597212},
doi = {10.1080/11038128.2025.2597212},
pmid = {41347697},
issn = {1651-2014},
mesh = {Humans ; *Activities of Daily Living ; Cross-Sectional Studies ; *COVID-19/rehabilitation/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; Adult ; SARS-CoV-2 ; Fatigue ; },
abstract = {BACKGROUND: Performance of activities of daily living (ADL) tasks is essential for most people's everyday lives. However, there is limited information regarding which ADL tasks and how their performances are typically impacted among persons with Long COVID.

AIM: To explore the types of ADL tasks typically affected and how the quality of ADL task performance is impacted in persons with long COVID and to explore relationships between ADL ability and health-related, social, or personal factors.

MATERIAL AND METHODS: This cross-sectional study involved individuals participating in a municipality-based rehabilitation program for persons with Long COVID. Data on ADL ability and health-related, social, and personal factors were gathered.

RESULTS: The sample included n = 30 individuals with Long COVID. The participants reported decreased quality of ADL task performance related to both Personal ADL and Instrumental ADL tasks. A moderate relationship was identified between participants' ADL-I ability measures and ratings of fatigue. None of the remaining health-related, social and personal variables were related to ADL ability.

CONCLUSIONS: Individuals diagnosed with Long COVID reported decreased quality of performance in both PADL and IADL tasks, with increased time and effort being the primary issues. The most prevalent symptom, fatigue, was moderately related to participants' ADL ability.},
}

Humans
*Activities of Daily Living
Cross-Sectional Studies
*COVID-19/rehabilitation/physiopathology/complications
Male
Female
Middle Aged
Aged
Adult
SARS-CoV-2
Fatigue

@article {pmid41347066,
year = {2025},
author = {Andreakos, E and Arkin, L and Bastard, P and Bolze, A and Borghesi, A and Brodin, P and Casanova, JL and Casari, G and Cobat, A and Drolet, B and Fellay, J and Hsieh, E and Meyts, I and Mogensen, TH and Sancho-Shimizu, V and Spaan, AN and Su, HC and Vinh, DC and Yatim, A and Zhang, Q and Zhang, SY and , },
title = {The seven enigmas of SARS-CoV-2: from the past to the future.},
journal = {Journal of human immunity},
volume = {1},
number = {4},
pages = {},
pmid = {41347066},
issn = {3065-8993},
abstract = {Five years ago, we launched the COVID Human Genetic Effort. Our goal was to explain the clinical variability among SARS-CoV-2-exposed individuals by searching for monogenic inborn errors of immunity (IEI) and their phenocopies. We deciphered the pathogenesis of critical COVID-19 pneumonia and multisystemic inflammatory syndrome in children (MIS-C) in ~15% and 2% of cases, respectively, thereby revealing general mechanisms of severe disease. We also defined neuro-COVID-19 genetically and immunologically in one child, while we delineated the immunological mechanisms of COVID-toes in healthy children and young adults, paving the way for their genetic study. Understanding the human genetic and immunological basis of resistance to SARS-CoV-2 infection, long COVID, and myocarditis post mRNA vaccination, has been challenging and investigations remain ongoing. This work highlights the power of patient-based basic research and large-scale international collaborative efforts to discover human genetic and immunological drivers of infectious disease phenotypes, with implications for the timely development of new medical strategies before the next pandemic arrives.},
}

@article {pmid41346576,
year = {2025},
author = {Guimarães, GN and Brunetti, NS and De Lima, DG and Proenca-Modena, JL and Farias, AS},
title = {Vaccination and COVID-19: impact on long-COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1686572},
pmid = {41346576},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention & control ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Vaccination ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long- and post-COVID-19 syndromes have emerged as a significant global health challenge, with millions of individuals experiencing persistent or the development of new symptoms after a long period of an initial SARS-CoV-2 infection. These symptoms are multisystemic and may indicate changes in the respiratory, neurological, cardiovascular and gastrointestinal systems, in addition to prolonged fatigue. Vaccination has played a crucial role in reducing severe disease and mortality, but the impact of the different vaccine combinations on the development and resolution of Long COVID remains a topic of debate. This review synthesizes current evidence on how different vaccine platforms, dosing strategies and booster doses influence the immunological response, protection, incidence, severity, and persistence of Long COVID symptoms. We discuss key immunological mechanisms by which vaccination may modulate and protect post-COVID syndrome outcomes, including its effects on viral clearance, immune response reprogramming, inflammation, and autoimmunity, seeking to combat misinformation and concepts spread by fake news. The review also highlights controversies and research gaps, such as variability in vaccine response among different populations and the role in the selection of more transmissible and virulent SARS-CoV-2 variants, as well as the potential differences between vaccine-induced and infection-induced immunity, and the role of pre-existing immune conditions in this scenario.},
}

Humans
*COVID-19/immunology/prevention & control
*COVID-19 Vaccines/immunology/administration & dosage
*SARS-CoV-2/immunology
*Vaccination
Post-Acute COVID-19 Syndrome

@article {pmid41345969,
year = {2025},
author = {Wei, H and Daniels, S and Wiggans, R and Coleman, A and Bramwell, D and McElvenny, D and Forde, D and van Tongeren, M},
title = {Long COVID and work in the UK: challenges, support and perspectives.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13690-025-01777-z},
pmid = {41345969},
issn = {0778-7367},
abstract = {AIM: Long COVID (LC) presents significant challenges for working age individuals, leading to major inequalities in access to work, employment and relevant support. This study investigates the workplace support provided to people with Long COVID (PwLC) in the UK, focusing on their return-to-work (RTW) experiences. It encompasses perspectives from both PwLC and managers of PwLC.

METHODS: Semi-structured interviews were conducted with 20 PwLC and two managers experienced in managing employees with LC. Inductive thematic analysis was performed using NVivo14.

FINDINGS: This qualitative research explored barriers and facilitators to supporting PwLC's RTW. LC is characterised by a wide range of mostly "invisible" and fluctuating symptoms and unpredictable recovery trajectories during which relapses can occur. Existing support mechanisms for RTW with LC include phased return, reduced hours, Occupational Health services, work adjustments, and government support. However, the study identified challenges in implementing these measures, such as unrealistic phased return plans, managers neglecting advice or guidance (e.g. from Occupational Health), unsuitable work adjustments and the burden of navigating government support. The financial impact of reduced hours or sick leave was one of the main reasons for returning to work. Both PwLC and managers highlighted significant gaps in knowledge, resources, policy and guidance for RTW support, emphasising the need for tailored support. Managers reported limited resources and inflexible policies as main challenges, which they addressed through creative solutions.

CONCLUSION: This qualitative study highlights potential barriers, challenges and gaps in supporting PwLC's RTW. To ensure equitable access to work for PwLC, a flexible and personalised approach is crucial, given the variability in LC symptoms and recovery rates. RTW support that fails to accommodate these characteristics may exacerbate symptoms or cause relapses. A supportive work environment is essential, as LC symptoms can be invisible and concerns about stigma may prevent PwLC from communicating openly and seeking support. Lack of resources is a major barrier for managers in supporting PwLC. Effective government support can potentially fill this gap but must be well-designed and implemented to reduce the burden on applicants.},
}

@article {pmid41344606,
year = {2025},
author = {Wee, LE and Tan, YY and Abdul Malek, MIB and Lim, JT and Chiew, CJ and Lye, DC and Tan, KB},
title = {Post-acute sequelae following Omicron COVID-19 in transplant recipients: a population-based cohort study.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2025.11.025},
pmid = {41344606},
issn = {1600-6143},
abstract = {Population-based studies evaluating long-COVID-19 prevalence in transplant recipients are limited. We examined risk of new-incident multi-systemic sequelae post-SARS-CoV-2 Omicron infection in a retrospective population-based cohort of transplant recipients, versus test-negatives. National COVID-19/healthcare-claims databases were utilised to construct cohorts of all Singaporean adult transplant recipients infected during Omicron-predominance (1[st] Jan-31[st] Dec 2022), and contemporaneous test-negatives. Competing risks regression (death as a competing risk), with overlap weights applied, was utilised to estimate risks of new-incident diagnoses/symptoms 31-300 days post-SARS-CoV-2 infection in transplant recipients, versus test-negatives. 1,890 SARS-CoV-2 infected transplant recipients and 1,482 test-negatives were included. 88.7% were boosted. Overall risks of post-acute sequelae were not significantly increased in SARS-CoV-2-infected transplant recipients, versus test-negatives (any post-acute diagnosis: adjusted-hazards-ratio, aHR=1.35[95%CI=0.74-2.45]; any post-acute symptom: aHR=1.06[95%CI=0.52-2.17]). However, increased risk of post-acute autoimmune (aHR=5.34[95%CI=1.03-27.62])/neurological sequelae (aHR=3.06[95%CI=1.23-7.61]) were observed in SARS-CoV-2-infected transplant recipients versus test-negatives; though excess-burden was modest (autoimmune: EB-per-1000-individuals=5.58[95%CI=-4.49-15.65]; neurological: EB-per-1000-individuals=19.82[95%CI=-4.33-43.96]). Risks of post-acute neurological/autoimmune sequelae remained elevated in untreated COVID-19 cases versus test-negatives but did not significantly differ in treated COVID-19 cases versus test-negatives. We conclude that overall risk of post-acute sequelae was not significantly elevated in a highly-vaccinated/boosted cohort of Omicron SARS-CoV-2-infected transplant recipients, versus test-negatives. COVID-19 vaccination/boosting remains important during endemicity.},
}

@article {pmid41343834,
year = {2025},
author = {Rayner, C and Clarke, J},
title = {The C19-YRSm questionnaire for Long COVID.},
journal = {Occupational medicine (Oxford, England)},
volume = {75},
number = {8},
pages = {477-479},
doi = {10.1093/occmed/kqaf057},
pmid = {41343834},
issn = {1471-8405},
}

@article {pmid41341512,
year = {2025},
author = {Quimby, AE},
title = {Editorial: Exploring neurotological health concerns post-COVID-19 infection.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1731001},
pmid = {41341512},
issn = {1664-2295},
}

@article {pmid41341487,
year = {2025},
author = {Fujii, R and Kanata, S and Watanabe, Y and Kunugi, H},
title = {A case of Klinefelter syndrome presenting with an acute psychotic episode after COVID-19 infection.},
journal = {PCN reports : psychiatry and clinical neurosciences},
volume = {4},
number = {4},
pages = {e70262},
pmid = {41341487},
issn = {2769-2558},
abstract = {BACKGROUND: Klinefelter syndrome (KS) is a disease caused by a 47, XXY sex chromosome abnormality. It has been reported that KS not only causes physical problems but also confers the risk of developing psychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.

CASE PRESENTATION: Here we present a case of an 18-year-old male with complete KS who developed an acute psychotic episode after COVID-19 infection. The patient presented a catatonic state with stupor, rejection of others, and hallucinations that led him to self-injury. Psychotic symptoms improved in about 2 months with an antipsychotic, aripiprazole.

CONCLUSION: To our knowledge, this is the first report of a KS patient who acutely developed a psychotic disorder after COVID-19. Vulnerability to psychotic conditions of KS likely manifests as an acute psychotic episode facilitated by the neurotropic effects of COVID-19.},
}

@article {pmid41338651,
year = {2025},
author = {Mazurik, K and Amah, A and Dumitrescu, DI and Ejalonibu, H and Chavda, B and Kemp, D and Frederick, DE and Mclean, C and Décary, S and Gruneir, A and Halas, G and Hoens, A and Kho, M and , and Groot, G},
title = {Developing a minimum dataset for a national patient registry on Long COVID in Canada: a Delphi consensus-based study.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e111474},
doi = {10.1136/bmjopen-2025-111474},
pmid = {41338651},
issn = {2044-6055},
mesh = {Humans ; Canada/epidemiology ; Delphi Technique ; *Registries ; *COVID-19/epidemiology/complications ; Consensus ; Quality of Life ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; *Datasets as Topic ; },
abstract = {OBJECTIVES: To develop survey items for a national patient registry on Long COVID using a modified Delphi process.

DESIGN: This study was based on a modified Delphi process involving three rounds of anonymous, online surveys to develop consensus on and prioritise survey elements to be included in a minimum dataset for use in a national patient registry in Canada. Initial Long COVID items were identified through an environmental scan of the literature.

SETTING: This study focused on healthcare systems in Canada and was conducted online.

PARTICIPANTS: A panel of 52 experts (patients, caregivers, clinicians and researchers) participated in all three rounds of the online survey. These participants were recruited through the Long COVID Web network and word of mouth.

RESULTS: In total, 243 survey elements related to care, quality of life and symptoms were included in round 1 of the survey. 200 reached consensus and moved to round 2 with two additional elements being developed based on open-ended responses. In round 2, participants ranked these survey elements and 34 advanced. In round 3, 33 survey elements met the threshold of consensus with one added a priori. The 33 survey elements were then used to develop a Long COVID minimum dataset, which consists of 48 items.

CONCLUSIONS: The findings affirm broad consensus for collecting data related to fatigue, post-exertional malaise, cardiovascular issues, respiratory problems and cognitive issues. This highlighted the desire for quality-of-life indicators and information related to care utilisation, quality and access.},
}

Humans
Canada/epidemiology
Delphi Technique
*Registries
*COVID-19/epidemiology/complications
Consensus
Quality of Life
SARS-CoV-2
Surveys and Questionnaires
Post-Acute COVID-19 Syndrome
*Datasets as Topic

@article {pmid41337380,
year = {2025},
author = {Kerezis, A and Antonoglou, A and Asimakos, A and Athanasiou, N and Spetsioti, S and Dalakleidi, K and Asvestas, P and Katsaounou, P and Golemati, S},
title = {A Machine Learning Framework for Efficient Triage of Long-COVID Patients to Specialists.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-4},
doi = {10.1109/EMBC58623.2025.11252756},
pmid = {41337380},
issn = {2694-0604},
mesh = {Humans ; *Triage/methods ; *COVID-19/diagnosis/therapy ; *Machine Learning ; SARS-CoV-2 ; Support Vector Machine ; Male ; Female ; Middle Aged ; },
abstract = {Long-COVID poses a significant burden on healthcare systems, necessitating efficient triaging strategies to optimise patient care. This study presents a machine learning (ML) framework for prioritising long-COVID patients for specialist consultations in cardiology, pulmonology, and psychiatry. Utilising a dataset of 175 patients, a Support Vector Machine model was developed, and subsequently enhanced with Synthetic Minority Oversampling Technique for class imbalance handling. The model yielded an accuracy of 0.67 and an Area-Under-the-Curve of 0.84, outperforming alternative models such as Random Forest, k-nearest neighbours, XGBoost, and Decision Trees. Notably, the SF-36 General Health score emerged as the most critical factor in patient classification, followed by bodily pain and anxiety levels. These findings demonstrate the potential of ML-based approaches to streamline healthcare resource allocation and improve patient outcomes. Future work will assess the clinical impact of this approach in prospective studies.Clinical Relevance- This study proposes a machine-learning-driven method to enhance specialist triaging for long-COVID patients, offering potential for improved healthcare resource allocation and timely patient care.},
}

Humans
*Triage/methods
*COVID-19/diagnosis/therapy
*Machine Learning
SARS-CoV-2
Support Vector Machine
Male
Female
Middle Aged

@article {pmid41332817,
year = {2025},
author = {Peng, B and Zhang, Y and Dalhuisen, T and Rogers, A and Estevez, J and Davies, HE and Jones, SA and Capric, V and Haddad, NS and Miners, KL and Ladell, K and Martin, JN and Kelly, JD and Deeks, SG and Peluso, MJ and Putrino, D and Price, DA and Dupont, CL and Freire, M and VanElzakker, MB and Proal, A and Scheuermann, RH and Lee, FE and Tan, GS and Qian, Y},
title = {Machine Learning Analysis of Post-Acute COVID Symptoms Identifies Distinct Clusters and Severity Groups.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.16.25340350},
pmid = {41332817},
abstract = {Questionnaires that capture patient-reported symptomatology provide low-cost but potentially high-value data for the de novo discovery of disease phenotype, severity, and responsiveness to intervention groupings within an umbrella condition. The availability of comprehensive electronic health records (EHRs) has nonetheless overshadowed the use of questionnaires data for symptom analysis in the context of COVID-19. We analyzed de-identified questionnaires from post-acute COVID-19 cohorts at the University of California, San Francisco (UCSF, n = 669), Icahn School of Medicine at Mount Sinai (ISMMS, n = 615), Emory University (Emory, n = 60), and the University Hospital of Wales (Cardiff, n = 317). Using topic modeling followed by unsupervised clustering, we identified distinct symptom clusters and their corresponding symptom signatures. Mapping these signatures to organ systems revealed nine to twelve endotypes per cohort, capturing the heterogeneity of post-COVID-19 symptoms. Some clusters were associated with pre-existing conditions, including a female-predominant severity cluster with neurological and hormonal symptoms. Longitudinal analysis distinguished three symptom trajectories: acute then resolving, persistent but attenuated, and progressive disease. Across all cohorts, three severity levels, namely, mild, moderate, and severe, were evident from symptoms alone. Symptom-based severity scores correlated with patient-reported health status (EQ-5D) and SARS-CoV-2-specific antibody responses in plasmablasts, validating the prediction. Cluster-level analyses further stratified patients into recovered and non-recovered subgroups, identifying endotypes associated with different recovery trajectories. Finally, meta-analysis integrating cohort-specific clusters defined ten global endotypes and a unified map of severity scores, highlighting cohort-specific patterns, sex differences, and relationships among organ systems. These findings demonstrate that machine learning-assisted screening of questionnaire data can robustly identify symptom clusters, endotypes, and severity groups, providing a framework for stratifying long COVID patients for precision medicine trial design.},
}

@article {pmid41332799,
year = {2024},
author = {Lee, H and Choi, S and Eom, E and Song, GH and Kim, SS},
title = {[Introduction to the Research Results of Coronavirus Disease 2019 Big Data (K-COV-N) and the Corresponding Utilization Plan].},
journal = {Jugan geon-gang gwa jilbyeong},
volume = {17},
number = {48},
pages = {2147-2159},
pmid = {41332799},
issn = {2586-0860},
abstract = {As part of the effort to establish a scientific basis for quarantine policies aimed at responding to new infectious diseases based on the experience of responding to coronavirus disease 2019 (COVID-19), the Korea Disease Control and Prevention Agency (KDCA) and National Health Insurance Service promoted the establishment of health information big data and signed a business agreement (April 29, 2021). The big data created by combining the KDCA's COVID-19 confirmed cases and vaccination data with the National Health Insurance Service's national health information are known as K-COV-N (KDCA Covid-19 NHIS cohort). The big data constructed were opened to the private sector through the National Health Insurance Service's open platform to promote private research. A cumulative total of 211 cases have been approved since the opening of COVID-19 big data from April 2022 until October 2, 2024, and a total of 30 papers have been published in international journals. The main contents were research results such as COVID-19 infection risk factors, vaccination effects, and long COVID. In addition, after the opening of big data, we held workshops on practical networking for utilizing COVID-19 big data to share analyses and techniques for utilizing the data. Additionally, we established a public-private data analysis network to promote exchanges between practitioners. In addition, we are contributing to the activation of private research by expanding ties with the National Cancer Center and health-information-holding organizations. Accordingly, the KDCA plans to continue opening up infectious disease-related information to develop evidence-based quarantine policies and support expert decision-making.},
}

@article {pmid41332658,
year = {2025},
author = {Pesqueira Sanchez, MA and de Necochea Campion, R and Dalhuisen, T and Fehrman, EA and Chhabra, PS and Kelly, JD and Martin, JN and Deeks, SG and Henrich, TJ and Peluso, MJ and LaRosa, SP},
title = {Increased mannosylation of extracellular vesicles in Long COVID plasma provides a potential therapeutic target for Galanthus nivalis agglutinin (GNA) affinity resin.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.21.689519},
pmid = {41332658},
issn = {2692-8205},
abstract = {There is no proven therapy for Long COVID, a post-acute illness characterized by a myriad of diverse symptoms including fatigue, dyspnea, and brain fog following SARS-CoV-2 infection. Extracellular vesicles (EVs) have been implicated in Long COVID pathogenesis by promoting viral and inflammatory signaling with their molecular cargo. In this study, we investigated whether EV abundance and glycome characteristics are altered in plasma from people with Long COVID and whether they can be targeted for removal using a glycan-binding affinity resin. Large (100-500 nm) and small (40-200 nm) EVs were isolated from plasma of participants in the post-acute phase of COVID-19 and analyzed by nanoparticle flow cytometry to measure concentration and glycan characteristics. Plasma of those with Long COVID contained elevated levels of both large and small EVs, and mannose-positive large EVs were significantly increased in comparison to recovered controls (p < 0.05). EV capture assays using Galanthus nivalis agglutinin (GNA) affinity resin demonstrated small EV removal positively correlated with mannose-positive EV abundance (r = 0.341, p < 0.05). NanoString analyses identified seven EV-associated miRNAs significantly depleted by GNA affinity resin treatment of plasma. PROGENy pathway inference of validated miRNA-mRNA interactions suggests these reductions may lead to a downregulation of JAK-STAT signaling and upregulation of Estrogen, VEGF, and PI3K pathways, resulting in a favorable rebalancing of immune and tissue-repair networks. These findings reveal specific glycome EV-miRNA cargo signatures in Long COVID and the potential clinical benefits of a lectin capture therapeutic strategy to remove these pathogenic vesicles and their inflammatory cargo.},
}

@article {pmid41332203,
year = {2025},
author = {Leighton, J and Heldmann, I and Van de Ven, K and Reis, L and Vijayakumar, A and Simpson, R and Nelson, M and Sheppard, C and Robinson, LL and Steinberg, R and Nguyen, M and Bayley, M and Daneman, N and Levy, C and Ho, C and Goulding, S and Hitzig, SL and Wasilewski, MB},
title = {Rehabilitation providers' experiences with long COVID care in Canada: a qualitative study.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09638288.2025.2583734},
pmid = {41332203},
issn = {1464-5165},
abstract = {PURPOSE: To examine the experiences, challenges, and recommendations of Canadian Rehabilitation Providers delivering care to people with Long COVID (PWLC), with the goal of informing best practices and guiding service and policy improvements.

MATERIALS AND METHODS: A qualitative descriptive study was conducted using semi-structured interviews with 32 Rehabilitation Providers from multiple disciplines and provinces across Canada. Participants were purposively sampled and interviewed between April 2022 and January 2023. Data were analyzed using codebook thematic analysis, incorporating inter-coder and inter-rater agreement and reflexivity practices.

RESULTS: Three central themes emerged: (1) Providers faced substantial barriers, including limited infrastructure, resource constraints, and misinformation about Long COVID; (2) In the absence of formal guidelines, providers adapted their practices through individualized care planning, trial-and-error, and peer learning; and (3) Participants emphasized key components of effective rehabilitation, such as validating patient experiences, promoting self-management and pacing, integrating caregiver support, facilitating peer connections, and fostering inter-professional collaboration.

CONCLUSION: Rehabilitation Providers have been critical in addressing the evolving needs of PWLC despite inadequate systemic support. Their insights point to the need for coordinated, interdisciplinary, and patient-centered care models, alongside investment in professional training, system infrastructure, and integrated policy responses for current and future post-viral conditions.},
}

@article {pmid41331993,
year = {2025},
author = {Palm, ME and Gu, CA and Bassett, IV and Levy, BD and Chen, LQ and John, J and Johnson, C and Lindsay, J and Lobb, R and McCray, N and Ojikutu, B and Martinez, LS and Rodriguez-Louis, J and Rushforth, A and Torres, R and Zionts, DL and Clark, CR},
title = {Community Engagement in Long Covid: Insights From the Boston COVID Recovery Cohort.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70493},
doi = {10.1111/hex.70493},
pmid = {41331993},
issn = {1369-7625},
support = {//This study was supported in part by a grant from the National Institutes of Health to fund the Researching COVID to Enhance Recovery (RECOVER) initiative, reference number 1OT2HL161847-01./ ; },
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology/therapy ; Boston/epidemiology ; *Community Participation/methods ; SARS-CoV-2 ; Cohort Studies ; Academic Medical Centers ; },
abstract = {BACKGROUND: In 2021, the National Institutes of Health launched a multi-centre observational study on long Covid: Researching COVID to Enhance Recovery (RECOVER). Six Boston academic medical centres joined community partners to become the Boston COVID Recovery Cohort (BCRC), a consortium of RECOVER sites. Our consortium developed a community engagement model, and this manuscript shares lessons and recommendations.

DESIGN AND PARTICIPANTS: The BCRC Community Partnership Table, which included community partners, senior equity leaders, academic researchers and health system collaborators, co-developed a charter to advance research, community education, clinical care, social support and institutional and policy change goals. BCRC engaged patients, providers, caregivers and legislators via multiple communication channels.

FINDINGS: The BCRC Community Partnership Table faced several challenges: working within a novel, evolving pandemic; structural barriers to successful community engagement; perspectives on trustworthiness of research; and working across multiple organisations with distinct structures, resources and goals. There were also successes: leaders who were invested in community engagement; a focus on inclusive network building; co-production; flexible communication channels; a shift to centring communities and patients; and connection with the legislature to support broader policy impacts.

DISCUSSION: To inform future community engagement models, we recommend the following: (1) healthcare research funders should build in time and resources for community engagement; (2) study consortia should include community engagement specialists in decision-making positions from the outset; and (3) community members should have prominent roles leading research engagement efforts.

CONCLUSIONS: Engagement models can enhance the equity impact of long Covid research. Reflections and recommendations in this paper can inform future efforts.

The project included community leaders, community-based organisations, people with long Covid, and those caring for people with long Covid. Community leaders, community-based organisations and people with long Covid are included in every aspect of the network. They inform decision-making, play a key role in network leadership and are also all represented within the authorship team.},
}

Humans
*COVID-19/rehabilitation/epidemiology/therapy
Boston/epidemiology
*Community Participation/methods
SARS-CoV-2
Cohort Studies
Academic Medical Centers

@article {pmid41331825,
year = {2025},
author = {Vicente-Gómez, JÁ and de Muniategui Climente, M and Loste, C and Barreales, S and Ríos, LR and Paredes, R and Mateu, L and Segui, FL},
title = {Post-COVID-19 condition patients' utilisation of healthcare resources after implementation of an integrated care unit.},
journal = {Cost effectiveness and resource allocation : C/E},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12962-025-00667-z},
pmid = {41331825},
issn = {1478-7547},
}

@article {pmid41326934,
year = {2025},
author = {O'Hare, AM and Montague, K and Hynes, DM and Fox, A and Nye, V and Iwashyna, TJ and Card, H and Tuepker, A and Helfand, M and Vig, EK and Butler, CR and Taylor, JS and Viglianti, EM and Jones, BE and Knight, SJ and Eaton, TL and Bowling, CB and Maciejewski, ML and Bohnert, AS and Ioannou, GN and Nugent, SM and , },
title = {Illness Experiences of Veterans Reporting Long-Term Symptoms or Health Challenges from COVID-19: Results from the VA COVID-19 Observational Research Collaboratory.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41326934},
issn = {1525-1497},
support = {C19 21-279//U.S. Department of Veterans Affairs/ ; },
abstract = {BACKGROUND: Our understanding of the illness experience of long COVID comes mostly from studies conducted among long COVID online communities and support groups or participants in cohort studies of COVID-19.

OBJECTIVE: To elicit the illness experiences of patients receiving care in real-world clinical settings experiencing ongoing symptoms or health challenges from COVID-19.

DESIGN AND PARTICIPANTS: Qualitative interview study conducted between July 2022 and April 2024 among 39 patients identified in health system data who indicated that they were experiencing ongoing symptoms or health challenges from COVID-19.

APPROACH: Qualitative analysis of participants' post-COVID-19 illness experience from one-time semi-structured in-depth interviews.

KEY RESULTS: Participants' mean age was 63.6 years (SD 13.2 years), 8 (20.5%) were identified in VA data as female, 6 (15.4%) as Black, 29 (74.4%) as White, and 2 (5.1%) as Hispanic. Interviews were conducted an average of 23 months after the initial COVID infection (range 8 to 49 months) and lasted an average of 87 (SD 27.3) minutes. Participants varied in their embrace of long COVID as an organizing framework for their post-COVID illness experience, reflecting two dominant themes: (1) Interpreting complexity: Study participants often had difficulty disentangling the long-term effects of COVID-19 from those of their other health conditions and normal aging. Their baseline health status, post-COVID illness trajectory, and expectations of aging shaped how they made sense of their illness experience; (2) Seeking answers: Though often fraught with uncertainty, participants' interpretation of their post-COVID illness experience was shaped more by clinical encounters and diagnostic evaluation than by interactions with others with relatable illness experiences.

CONCLUSIONS: Our findings illuminate the challenges of applying a broadly defined diagnostic category lacking condition-specific markers in real-world clinical settings and the role of health systems and providers in the ongoing social construction of long COVID.},
}

@article {pmid41325417,
year = {2025},
author = {Pinero, S and Li, X and Liu, L and Li, J and Lee, SH and Winter, M and Nguyen, T and Zhang, J and Le, TD},
title = {Integrative multi-omics framework for causal gene discovery in long COVID.},
journal = {PLoS computational biology},
volume = {21},
number = {12},
pages = {e1013725},
doi = {10.1371/journal.pcbi.1013725},
pmid = {41325417},
issn = {1553-7358},
abstract = {Long COVID, or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), affects an estimated 10-20% of patients and presents persistent multisystemic symptoms. Although demographic and clinical factors, such as age, sex, and comorbidities, contribute to risk, the genetic mechanisms underlying this risk remain poorly defined. To address this gap, we developed a multi-omics framework that integrates Transcriptome-Wide Mendelian Randomization (TWMR), Control Theory (CT), Expression Quantitative Trait Loci (eQTL), Genome-Wide Association Studies (GWAS), RNA sequencing (RNA-seq), and Protein-Protein Interaction (PPI) network to identify putative causal genes and network drivers in Long COVID. Our approach prioritized 32 candidate genes, including 19 previously reported and 13 novel, with roles in the SARS-CoV-2 response, viral carcinogenesis, immune regulation, and cell cycle control. Enrichment analyses revealed a shared genetic architecture in syndromic, metabolic, autoimmune, and connective tissue disorders. Using causal gene expression profiles, we identified three distinct symptom-based subtypes of Long COVID, providing information on the heterogeneity of disease mechanisms and clinical presentation. Finally, we developed an open-source Shiny application for interactive exploration of these findings. Together, this integrative framework highlights novel causal mechanisms and therapeutic targets, advancing precision medicine strategies for Long COVID.},
}

@article {pmid41324571,
year = {2025},
author = {Metaxaki, M and Ram, R and Perera, M and Wills, M and Krishna, BA and Sithole, N},
title = {Robust antibody and T cell responses tracked longitudinally in patients with long COVID.},
journal = {The Journal of general virology},
volume = {106},
number = {12},
pages = {},
doi = {10.1099/jgv.0.002172},
pmid = {41324571},
issn = {1465-2099},
mesh = {Humans ; *COVID-19/immunology/virology ; *Antibodies, Viral/blood/immunology ; Male ; Female ; *SARS-CoV-2/immunology ; Middle Aged ; Interferon-gamma/blood/immunology ; Retrospective Studies ; Antibodies, Neutralizing/blood/immunology ; Interleukin-2/immunology/blood ; Aged ; *T-Lymphocytes/immunology ; Adult ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; },
abstract = {After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a minority of patients experience persistent or emerging symptoms, termed 'long coronavirus disease (COVID)' or post-acute sequelae of COVID-19. The molecular causes of long COVID remain unclear, but disrupted immune functions, such as inflammation and immune deficit, have been posited as factors. In this retrospective cohort study, we measured markers of immune function in a group of patients with long COVID up to 40 months post infection. As proxies for immune function, we measured serum antibody levels, antibody neutralizing capability and production of IFN gamma (IFN-γ) and IL-2 against SARS-CoV-2 and other viral peptides. As expected, serum antibody levels increased over time with vaccinations and reinfections with later variants of SARS-CoV-2. Patients also showed corresponding increasing SARS-CoV-2-specific IL-2 responses and stable IFN-γ responses. We observed no significant differences in immune responses among patients with ongoing long COVID, those who had recovered from it or individuals who recovered from acute COVID-19. Overall, we found no indication of a reduction in these aspects of immune function after SARS-CoV-2 infection. This study provides a valuable foundation for further research aimed at understanding the causes of long COVID.},
}

Humans
*COVID-19/immunology/virology
*Antibodies, Viral/blood/immunology
Male
Female
*SARS-CoV-2/immunology
Middle Aged
Interferon-gamma/blood/immunology
Retrospective Studies
Antibodies, Neutralizing/blood/immunology
Interleukin-2/immunology/blood
Aged
*T-Lymphocytes/immunology
Adult
Longitudinal Studies
Post-Acute COVID-19 Syndrome

@article {pmid41323230,
year = {2025},
author = {Furevik, LL and Lapina, O and Lindland, ES and Høgestøl, EA and Geier, OM and Devik, K and Farmen, AH and Flemmen, HØ and Harbo, HF and Morsund, ÅH and Novotny, V and Ofte, HK and Pedersen, KO and Popperud, TH and Ratajczak-Tretel, B and Samsonsen, C and Selnes, P and Torkildsen, Ø and Undseth, RM and Aamodt, AH and Beyer, MK and Boldingh, MI},
title = {Brain MRI findings in patients with post COVID-19 condition: frequency and longitudinal changes in a nationwide cohort study.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1662263},
pmid = {41323230},
issn = {1664-2295},
abstract = {BACKGROUND: Prolonged neurological symptoms following COVID-19 are common, yet few longitudinal studies describe brain MRI findings in this patient group. The use of contrast enhanced sequences is particularly lacking. We address this knowledge gap by reporting the frequency and longitudinal changes in brain MRI findings among patients with post COVID-19 condition exhibiting neurological symptoms.

METHODS: This prospective multicenter study included 140 adult patients referred for persistent neurological symptoms following COVID-19. Brain MRI was performed at both 6 and 12 months after infection onset, reporting white matter hyperintensities, cerebral microbleeds, and additional pathological findings including contrast enhancement. White matter hyperintensities were compared with a healthy control group.

RESULTS: The prevalence of white matter hyperintensities was comparable to healthy controls, and microbleeds were found at rates comparable to population studies, with longitudinal changes being infrequent. Lesions consistent with inflammation or demyelination were present in 4% (5/120) of patients at 6 months. Cranial nerve enhancement was found in 7% (7/94) of patients, persisting up to 12 months, predominantly affecting the oculomotor nerve. However, enhancement occurred without clinically detected ocular muscle paresis.

CONCLUSION: Our findings indicate that brain MRI primarily serves to exclude differential diagnoses in post COVID-19 condition, with limited clinical benefit of repeated imaging in the absence of new symptoms. However, signs of long-term inflammatory processes can be observed, and detection is improved by contrast enhanced sequences.},
}

@article {pmid41322411,
year = {2025},
author = {Liu, H and Xu, Z and Karsidag, I and Wang, P and Weng, J},
title = {Correction: Immune cell communication networks and memory CD8+ T cell signatures sustaining chronic inflammation in COVID-19 and Long COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1739646},
doi = {10.3389/fimmu.2025.1739646},
pmid = {41322411},
issn = {1664-3224},
abstract = {[This corrects the article DOI: 10.3389/fimmu.2025.1689507.].},
}

@article {pmid41319836,
year = {2025},
author = {Li, Y and Tao, Y and Zhao, Z and Zhong, P and Zhong, L and Yang, H and Yu, M and Liu, S and Lei, K and Zhao, Q and Wang, R and Wang, J and Zeng, Q and Kuang, S and Li, T},
title = {Long COVID as an Independent Predictor of Myasthenia Gravis Exacerbation: A Prospective Cohort Study Integrating Machine Learning for Risk Stratification.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108554},
doi = {10.1016/j.rmed.2025.108554},
pmid = {41319836},
issn = {1532-3064},
abstract = {OBJECTIVES: This study evaluates the impact of long coronavirus disease (Long COVID) on disease exacerbation in patients with myasthenia gravis (MG) and leverages machine learning (ML) approaches to identify high-risk patients.

METHODS: Patients with MG and COVID-19 co-infection were recruited from December 5, 2022, to January 20, 2023, at the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine (ChiCTR2400087937). Participants underwent structured interviews at 1, 6, and 12 months post-COVID-19 to assess the incident Long COVID and MG exacerbation. The primary outcomes included the incidence and severity of MG exacerbation; the secondary outcome was 12-month mortality. Cox proportional hazards regression was employed to explore the correlation between Long COVID and MG exacerbation. ML algorithms were implemented for predictive modeling.

RESULTS: Among 180 patients, 62 (34.4%) experienced MG exacerbation within 12 months, and severe exacerbations (MG-ADL ≥ 6 points) accounted for 43.5% of cases. Among those with initial MG exacerbations, 14.4% continued to exhibit persistent symptoms without full recovery by the 12-month follow-up. Six fatalities (3.3%) were recorded. Long COVID served as the strongest predictor of exacerbation (aHR = 2.55, 95% CI 1.47-4.42, P = 0.001), followed by acetylcholinesterase (AChE) inhibitor use (aHR = 2.38) and severe COVID-19 classification (aHR = 2.30). The Random Forest model (RF) outperformed other algorithms, achieving an AUC of 0.83, with Long COVID as the top predictive feature.

CONCLUSIONS: Long COVID is associated with MG exacerbation over time. RF model shows potential as a scalable tool for MG exacerbation risk stratification.},
}

@article {pmid38400050,
year = {2024},
author = {Fernández-de-Las-Peñas, C and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Torres-Macho, J and Ryan-Murua, P and Franco-Moreno, AI and Pellicer-Valero, OJ and Arendt-Nielsen, L and Giordano, R},
title = {Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.},
journal = {Viruses},
volume = {16},
number = {2},
pages = {},
pmid = {38400050},
issn = {1999-4915},
support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/genetics ; Interleukin-10/genetics ; Interleukin-6/genetics ; Membrane Proteins/genetics ; Polymorphism, Single Nucleotide ; RNA-Binding Proteins/genetics ; SARS-CoV-2/genetics ; *Tumor Necrosis Factor-alpha/genetics ; },
abstract = {The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252, were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*COVID-19/genetics
Interleukin-10/genetics
Interleukin-6/genetics
Membrane Proteins/genetics
Polymorphism, Single Nucleotide
RNA-Binding Proteins/genetics
SARS-CoV-2/genetics
*Tumor Necrosis Factor-alpha/genetics

@article {pmid37887751,
year = {2023},
author = {Fernández-de-Las-Peñas, C and Guijarro, C and Torres-Macho, J and Pellicer-Valero, OJ and Franco-Moreno, A and Nijs, J and Velasco-Arribas, M},
title = {Serological Biomarkers at Hospital Admission and Hospitalization Treatments Are Not Related to Sensitization-Associated Symptoms in Patients with Post-COVID Pain.},
journal = {Pathogens (Basel, Switzerland)},
volume = {12},
number = {10},
pages = {},
pmid = {37887751},
issn = {2076-0817},
support = {LONG-COVID-EXP-CM//Consejería de Economía, Empleo y Competitividad Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; },
abstract = {Current evidence suggests that a group of patients who had survived coronavirus disease, 2019 (COVID-19) and developed post-COVID pain can exhibit altered nociceptive processing. The role of serological biomarkers and hospitalization treatments in post-COVID pain is unclear. This study aimed to investigate the association of serological biomarkers and treatments received during hospitalization with sensitization-associated symptoms in COVID-19 survivors with post-COVID pain. One hundred and eighty-three (n = 183) patients who had been hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed in a face-to-face interview 9.4 (SD 3.4) months after hospitalization. Levels of 19 serological biomarkers, hospitalization data, and treatments during hospitalization were obtained from hospital records. Sensitization-associated symptoms (Central Sensitization Inventory, CSI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophism (Pain Catastrophizing Scale), and anxiety/depressive level (Hospital Anxiety and Depression Scale, HADS) were assessed. The prevalence of post-COVID pain was 40.9% (n = 75). Twenty-nine (38.6%) patients had sensitization-associated symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence of sensitization-associated symptoms. The analysis revealed that patients with sensitization-associated symptoms exhibited higher lymphocyte count and lower urea levels than those without sensitization-associated symptoms, but differences were small. Pain catastrophism and depressive levels, but not fatigue, dyspnea, brain fog, anxiety levels, or poor sleep, were higher in individuals with sensitization-associated symptoms. In conclusion, this study revealed that sensitization-associated post-COVID pain symptoms are not associated with serological biomarkers at hospital admission and hospitalization treatments received.},
}

@article {pmid36009498,
year = {2022},
author = {Fernández-de-Las-Peñas, C and Cancela-Cilleruelo, I and Moro-López-Menchero, P and Rodríguez-Jiménez, J and Gómez-Mayordomo, V and Torres-Macho, J and Pellicer-Valero, OJ and Martín-Guerrero, JD and Hernández-Barrera, V and Arendt-Nielsen, L},
title = {Prevalence of Musculoskeletal Post-COVID Pain in Hospitalized COVID-19 Survivors Depending on Infection with the Historical, Alpha or Delta SARS-CoV-2 Variant.},
journal = {Biomedicines},
volume = {10},
number = {8},
pages = {},
pmid = {36009498},
issn = {2227-9059},
support = {THE LONG-COVID-EXP-CM//Comunidad de Madrid/ ; 0067235//Novo Nordisk Foundation/ ; },
abstract = {We compared the prevalence of musculoskeletal post-COVID pain between previously hospitalized COVID-19 survivors infected with the historical, Alpha or Delta SARS-CoV-2 variant. Data about musculoskeletal post-COVID pain were systematically collected through a telephone interview involving 201 patients who had survived the historical variant, 211 who had survived the Alpha variant and 202 who had survived the Delta variant six months after hospital discharge. Participants were recruited from non-vaccinated individuals hospitalized due to SARS-CoV-2 infection in one hospital of Madrid (Spain) during three different waves of the pandemic (historical, Alpha or Delta variant). Hospitalization and clinical data were collected from hospital medical records. In addition, anxiety/depressive levels and sleep quality were also assessed. The prevalence of musculoskeletal post-COVID pain was higher (p = 0.003) in patients infected with the historical variant (47.7%) than in those infected with the Alpha (38.3%) or Delta (41%) variants. A significantly (p = 0.002) higher proportion of individuals infected with the historical variant reported generalized pain (20.5%) when compared with those infected with the other variants. The prevalence of new-onset post-COVID musculoskeletal pain reached 80.1%, 75.2% and 79.5% of patients infected with the historical, Alpha or Delta variants, respectively. No specific risk factors for developing post-COVID pain were identified depending on the SARS-CoV-2 variant. In conclusion, this study found that musculoskeletal post-COVID pain is highly prevalent in COVID-19 survivors six months after hospital discharge, with the highest prevalence and most generalized pain symptoms in individuals infected with the historical variant. Approximately 50% developed "de novo" post-COVID musculoskeletal pain symptoms.},
}

@article {pmid41318861,
year = {2025},
author = {Yadav, JP and Yadav, S and Dubey, NK and Yadav, IP and Pathak, P and Verma, A},
title = {Lingering echoes of SARS-CoV-2: mechanistic insights and management of long COVID syndrome.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41318861},
issn = {1568-5608},
abstract = {Throughout the world-wide COVID-19 pandemic, there has arisen a significant and a sustained public-health issue, whereby a significant proportion of individuals report persistent symptoms, well beyond the acute period of infection. The non-united array of chronic, multisystemic events, such as fatigue, cognitive deficit, respiratory dysfunction, cardiovascular abnormalities, and neuropsychiatric disorders characterize this sequela, which is referred to as LCS. LCS is much more than the starting viral insult, as it causes long-term complications that impact various organ systems. The current review questions the pathophysiological mechanisms of LCS, including scrutinizing the importance of the dysregulation of immunity, the persistence of viral reservoirs, endothelial dysfunction, autonomic imbalance, and mitochondrial injury. We highlight the heterogeneity of the syndrome and the associated diagnostic and treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies, including pharmacologic therapy (immunomodulators, anticoagulants, antiviral medications, etc.) and non-pharmacologic treatment (rehabilitative programs, etc.) are discussed against the backdrop of recent clinical findings. This review incorporates the recent literature and presents a review of potential treatment options that alleviate symptoms and improve the quality of life of LCS patients. Finally, this integrated synthesis can be used by both clinicians and researchers to gain practical information on the diagnosis, treatment, and future treatment directions of LCS.},
}

@article {pmid41316208,
year = {2025},
author = {Ouazana Vedrines, C and Gouraud, C and Scherlinger, M and Betouche, S and Carrat, F and Caumes, E and Pitron, V and Robineau, O and Sibilia, J and Thoreux, P and Xiang, K and Ranque, B and Lemogne, C and , },
title = {Excess of infection with SARS-CoV-2 during the first versus second wave of the COVID-19 pandemic among patients with long COVID.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-025-25417-x},
pmid = {41316208},
issn = {1471-2458},
}

@article {pmid41316170,
year = {2025},
author = {Joy, M and Adams, N and Yanuck, M and Dossett, ML},
title = {Experiences with Qi and changes in post-acute sequelae of COVID-19 (PASC) symptoms with qigong: a qualitative analysis of participants' experiences in a pilot clinical trial.},
journal = {BMC complementary medicine and therapies},
volume = {25},
number = {1},
pages = {434},
pmid = {41316170},
issn = {2662-7671},
mesh = {Humans ; *Qigong/methods ; Pilot Projects ; *COVID-19/complications/therapy ; Male ; Female ; Middle Aged ; Adult ; Qualitative Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Aged ; Quality of Life ; },
abstract = {BACKGROUND: Commonly known as "long COVID", post-acute sequelae of COVID-19 (PASC) is a chronic condition with no validated treatment that significantly impacts the quality of life of those affected. Qigong is a Traditional Chinese Medicine (TCM) practice that may serve as a possible therapeutic approach for PASC. This study explored participants' experiences with qi, and changes in PASC symptoms, following participation in a clinical trial of group-based, combined external and internal qigong for individuals with PASC.

METHODS: A qualitative study of 26 individuals who participated in a pilot feasibility trial of qigong for PASC symptoms was performed. Participants engaged in six weekly, two-hour sessions of external and internal qigong delivered in a group-based format. Upon completion of the intervention, all participants were interviewed using a semi-structured interview guide. The interviews were transcribed, coded and analyzed using a conventional content analysis approach to explore participants' perceptions and understanding of qi, qigong, and the overall impact of the sessions on their well-being and PASC symptoms.

RESULTS: Participants' understanding and explanations of qi varied. Almost all participants (92%) reported feeling qi during the sessions, and a variety of different sensations associated with perception of qi were described. Approximately three-quarters of participants experienced improvement in one or more PASC symptoms, most commonly fatigue, "brain fog", and sleep quality, and 85% reported improved well-being. Additionally, participants frequently cited the group-based nature of the intervention as a positive aspect of their experience.

CONCLUSIONS: The qigong intervention was well-received by participants, with the majority perceiving qi and reporting improvements in PASC-related symptoms and overall well-being. These findings suggest that many individuals may be able to perceive qi and that group-delivered combined external and internal qigong may be a beneficial complementary therapy for managing PASC symptoms. As this is a pilot study with a small sample size and a single qigong teacher, results must be interpreted cautiously. Further research is warranted to evaluate the effects of qigong in this patient population.

TRIAL REGISTRATION: Registry: ClinicalTrials.gov. Trial Registration Number: NCT05675995. Date of Registration: January 4, 2023.},
}

Humans
*Qigong/methods
Pilot Projects
*COVID-19/complications/therapy
Male
Female
Middle Aged
Adult
Qualitative Research
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Aged
Quality of Life

@article {pmid41316069,
year = {2025},
author = {Spielmann, J and Pink, I and Framme, C and Tode, J and Volkmann, I},
title = {Association of foveal avascular zone (FAZ) enlargement with SARS-CoV-2 infection and long COVID-19.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-025-04528-4},
pmid = {41316069},
issn = {1471-2415},
abstract = {BACKGROUND: As COVID-19 was found to affect small vessels of multiple organ systems, the purpose of the study is to describe the macular vessel density (VD) and the area of the foveal avascular zone (FAZ) by optical coherence tomography angiography (OCTA) in patients who recovered from a COVID-19 disease, who were or were not treated in an Intensive Care Unit (ICU) and who suffer from fatigue due to long COVID.

METHODS: Prospective case-control study in which laboratory-confirmed and recovered COVID-19 patients were included. Macular OCTA was performed at least seven weeks after initial COVID-19. The VD of the superficial retinal capillary plexus (SCP) and the area of the FAZ were measured. Results were compared among ICU- and non-ICU COVID-19 patients and a healthy control group; moreover, patients were divided into groups of no fatigue, fatigue, and extreme fatigue and results were compared among these and a control group.

RESULTS: FAZ of non-ICU patients was significantly enlarged compared to control group. VD was not significantly different among these cohorts. FAZ of fatigue group was significantly enlarged compared to no fatigue group and control group. VD of extreme fatigue group was significantly greater than VD of both no fatigue group and control group.

CONCLUSION: The retinal microvasculature of recovered COVID-19 patients showed alterations in the sense of a significantly enlarged FAZ, particularly in patients with mild disease and fatigue. These microvascular manifestations may lead to future complications or visual impairment. Performing macular OCTA could be a possible monitoring tool for microvascular changes in these patients and a predictor for long COVID fatigue.},
}

@article {pmid41314260,
year = {2025},
author = {Felix, DM and Mohandas, VJ and de Andrade Leão, OA and Siqueira, FV and Hallal, PC},
title = {Physical activity and post-COVID symptoms: Findings from the EPICOVID 2.0 survey in Brazil.},
journal = {Preventive medicine},
volume = {},
number = {},
pages = {108471},
doi = {10.1016/j.ypmed.2025.108471},
pmid = {41314260},
issn = {1096-0260},
abstract = {OBJECTIVE: This study primarily aims to analyze changes in physical activity after the COVID-19 pandemic in Brazil and their association with post-COVID symptoms. We also examined associations between sociodemographic variables (sex, region, wealth quintile, education, age, and race/ethnicity) and physical activity.

METHODS: Using data from the 2024 Brazilian national survey EPICOVID 2.0, with 33,250 participants, we analyzed self-reported changes in physical activity during the pandemic. To test associations between four categories ("Never Practiced" as reference category, "Decreased", "Maintained", or "Increased") and 14 post-COVID symptoms, we used adjusted Logistic regression models. Establishing a threshold of p < 0.004, after Bonferroni correction.

RESULTS: The "Maintained" physical activity group had a significantly lower proportion of tiredness, Odds Ratio [95 % CI] = 0.57[0.39, 0.83], and joint pain, OR [95 % CI] = 0.61 [0.44, 0.84]. Even though not statistically significant, the "Decreased" activity group showed higher odds of some post-COVID symptoms.

CONCLUSION: Compared to the reference group, participants who maintained some level of physical activity during the pandemic have lower odds of presenting some post-COVID symptoms. Results highlight the importance of sustained engagement in physical activity and the need for targeted interventions to promote equitable access.},
}

@article {pmid41313894,
year = {2025},
author = {Chau, SL and Hung, IFN and Luk, TT and Chan, SSC},
title = {The impacts of long COVID and booster doses of post-infection vaccination among hospital-discharged COVID-19 survivors in Hong Kong: A retrospective observational study.},
journal = {Vaccine},
volume = {70},
number = {},
pages = {128022},
doi = {10.1016/j.vaccine.2025.128022},
pmid = {41313894},
issn = {1873-2518},
abstract = {BACKGROUND: This study examined the prevalence of long COVID, risk factors, vaccination status, and health-related quality of life in hospital-discharged individuals with a history of COVID-19 infection in Hong Kong.

METHODS: This is a retrospective observational study. A convenience sampling was used to recruit individuals with a history of COVID-19 infection from a university teaching hospital in Hong Kong. 717 out of 1771 individuals aged 18 years or above with COVID-19 infection (confirmed by polymerase chain reaction/rapid antigen test) and hospitalized during the COVID-19 outbreak completed the telephone follow-up between January 2023 and March 2025. The prevalence of long COVID (defined by the WHO), risk factors, vaccination status, and health-related quality of life were analyzed. The proportions were weighted by the sex and age distribution of Hong Kong adults in 2023.

RESULTS: The mean age of participants was 46.8 years (±17.4), and 67.4 % were men. The most prevalent long COVID symptoms were shortness of breath (10.8 %), persistent fatigue (9.8 %), forgetfulness (9.5 %), and persistent dry cough (4.3 %). 52.3 % of participants received three vaccine doses after contracting COVID-19, and 71.3 % of them received BioNTech. Participants who experienced shortness of breath, persistent fatigue, and forgetfulness had poorer health-related quality of life, as indicated by lower scores on the EuroQol-visual analog scales and the Physical and Mental Component Scores of the VR-12 (all P < 0.05). Participants who received booster doses (at least three doses) were associated with lower odds of experiencing long COVID symptoms, including shortness of breath, persistent fatigue, forgetfulness, and persistent dry cough (all P < 0.05).

CONCLUSIONS: The prevalence of long COVID was low among the hospital-discharged individuals, and booster doses of post-infection vaccination might reduce the risk of experiencing these symptoms. Further investigation is needed to examine the underlying mechanisms of long COVID and how these risks can be mitigated.},
}

@article {pmid41312347,
year = {2025},
author = {Singh, AK and Kumar, K and Singh, M and Jagawat, T and Nathiya, D and Singh Tomar, B and Jagawat, S and Jimenez, M and Lopez, M and Miller, J and Koralnik, IJ},
title = {Neuropsychiatric manifestations of Long COVID in India: a persistent problem 2.5 years after disease onset.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1704801},
pmid = {41312347},
issn = {1664-2295},
abstract = {BACKGROUND: Long COVID, also called post-acute sequelae of SARS-CoV-2 infection (PASC), is a multi-system syndrome affecting millions of people worldwide. Neuropsychiatric manifestations of Long COVID are particularly debilitating; however, they have not been reported in detail from India.

METHODS: This cross-sectional study compared the demographics, comorbidities, symptoms, and neuropsychiatric profiles of patients with Long COVID symptoms that began within 3 months of the initial SARS-CoV-2 infection and persisted for approximately 2.5 years at the time of evaluation. The study was conducted at NIMS University (Jaipur, Rajasthan, India).

RESULTS: Of 1,085 participants, 521 had COVID-19 pneumonia requiring hospitalization, while 564 had a mild initial respiratory presentation and were never hospitalized. On average 2.5 years after acute infection, our principal finding is that Long COVID differs based on initial disease severity. Post-hospitalization patients were older than the non-hospitalized group (43.24 vs. 36.15 years; p < 0.0001), had a higher body-mass index, and a more frequent prior history of lung disease (7.7% vs. 2.7%; p < 0.001). Overall, 69.6% of participants had at least one neurologic symptom, including myalgia (18.5%), dizziness (17.3%), headache (16.6%), pain (15.7%), anosmia (13.3%), brain fog (9.4%), numbness (6.0%), tinnitus (5.5%), and dysgeusia (3.7%), with only dizziness being more frequent in the post-hospitalization than the non-hospitalized group (20.3% vs. 14.5%; p = 0.012). Conversely, non-hospitalized patients had more frequent fatigue (23.2% vs. 6.0%; p < 0.0001), sleep problems (18.4% vs. 7.7%; p < 0.0001), chest pain (8.2% vs. 2.9%; p < 0.0001), and gastrointestinal symptoms (7.8% vs. 2.9%; p < 0.0001), while post-hospitalization patients more frequently complained of shortness of breath (9.6% vs. 2.7%; p < 0.0001). Overall, 4.9% of participants had cognitive dysfunction on the MMSE test, while 10.4% suffered from stress, and 12.7 and 9.2% had anxiety and depression symptoms, respectively, on DASS assessment, without significant differences between the two groups.

CONCLUSION: Our study highlights differences in demographics and clinical presentation of Long COVID between post-hospitalization and non-hospitalized individuals in India. The high frequency of neurologic manifestations 2.5 years after disease onset underscores the need for early detection and targeted interventions.},
}

@article {pmid41309532,
year = {2025},
author = {Shakib, SH and Antimisiaris, D},
title = {Analysis of polypharmacy in older adults pre and post COVID-19.},
journal = {Expert review of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17512433.2025.2596347},
pmid = {41309532},
issn = {1751-2441},
abstract = {BACKGROUND: Increased diagnoses burden is a characteristic of post COVID sequelae. Concomitant increased polypharmacy burden is a consequence yet there are few publications on the topic. The aim of this report is to help characterize post COVID polypharmacy in older adults.

RESEARCH DESIGN AND METHODS: Using data from a large health system, pre and post COVID disease and medication burden was analyzed. Within-person difference was tested. Multiple linear regression determined predictive post COVID increases in clinical burden. Qualitative characterization was supported by multidisciplinary literature review.

RESULTS: In patients ≥61 years the mean increase in diagnoses and medications per post COVID patient was 7.37 and 13.23 respectively. The largest increase in diagnoses was seen in patients aged 71-80 and people of Black race. The largest increase in medications was in patients aged 81-90 and females. Each additional pre-covid diagnosis and medication was associated with a 0.10 unit, and 0.12 unit increase respectively post-COVID-19.

CONCLUSIONS: Each pre-COVID diagnoses and medication were associated with quantifiable increase post-COVID, with higher risk with advanced age, Black race and female gender. Single health system data may inhibit generalizability of our findings. Clinicians should be vigilant and prepared to manage post COVID-19 polypharmacy.},
}

@article {pmid41308689,
year = {2025},
author = {Amdal, CD and Falk, RS and Alanya, A and Schlichting, M and Roychoudhury, S and Bhatnagar, V and Wintner, LM and Regnault, A and Ingelgård, A and Coens, C and le Cessie, S and Holzner, B and Chang, J and Taphoorn, M and Cislo, P and Giesinger, JM and Cappelleri, JC and Pawar, V and Ten Seldam, S and Papadopoulos, EJ and Calvert, MJ and Joseph, KL and Bottomley, A and Griebsch, I and Arraras, JI and Astrup, GL and Basch, E and Belančić, A and Brundage, M and Campbell, A and Rerhou Rantell, K and Cocks, K and Cherny, N and Eremenco, S and Ferrer, M and Fiero, MH and Gerlinger, C and Goetghebeur, E and Grouven, U and Lauer, A and Aiyegbusi, OL and Machingura, A and Mizusawa, J and Molenberghs, G and Aa Petersen, M and Reijneveld, JC and Ringash, J and Rumpold, G and Rutherford, C and Quinten, C and Sail, K and Sasseville, M and Sauerbrei, W and Schiel, A and Smith, AW and Snyder, C and Velikova, G and Wang, XS and Bjordal, K and Pe, M and , },
title = {SISAQOL-IMI consensus-based guidelines to design, analyse, interpret, and present patient-reported outcomes in cancer clinical trials.},
journal = {The Lancet. Oncology},
volume = {26},
number = {12},
pages = {e683-e693},
doi = {10.1016/S1470-2045(25)00520-0},
pmid = {41308689},
issn = {1474-5488},
mesh = {Humans ; *Patient Reported Outcome Measures ; *Neoplasms/therapy/drug therapy ; Consensus ; Quality of Life ; *Research Design/standards ; *Clinical Trials as Topic/standards ; Randomized Controlled Trials as Topic/standards ; },
abstract = {Standardising the implementation of patient-reported outcomes (PROs) in clinical trials is crucial for evaluating the benefits and risks of cancer treatments. The Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) has developed 146 consensus-based recommendations for designing, analysing, interpreting, and presenting PROs in cancer clinical trials. This initiative, undertaken from 2021 to 2025, involved experts, including statisticians, PRO measurement experts, clinicians, and patient representatives from 41 organisations representing regulatory agencies, academia, the pharmaceutical industry, health-technology assessment bodies, and patient advocates. SISAQOL-IMI provides guidance on the implementation of PROs in randomised controlled trials and single-arm trials, terminology, definitions and the selection of PRO score interpretation thresholds, and for visualising PRO results for different audiences. To facilitate the implementation of these standards, in addition to this Policy Review, four key outputs are available: an interactive table, a guidebook, plain language materials, and a glossary.},
}

Humans
*Patient Reported Outcome Measures
*Neoplasms/therapy/drug therapy
Consensus
Quality of Life
*Research Design/standards
*Clinical Trials as Topic/standards
Randomized Controlled Trials as Topic/standards

@article {pmid41305454,
year = {2025},
author = {Miftahof, J and Bernauer, B and Tan, CS},
title = {Neurological Manifestations of SARS-CoV-2.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/v17111432},
pmid = {41305454},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; Animals ; *SARS-CoV-2/pathogenicity ; Disease Models, Animal ; Brain/virology/pathology ; *Nervous System Diseases/virology/pathology/etiology ; Central Nervous System/virology/pathology ; },
abstract = {Neurocognitive symptoms have emerged as notable sequelae of SARS-CoV-2 infection (COVID-19). Although primarily a respiratory virus, SARS-CoV-2 has been associated with central nervous system (CNS) changes observed in both clinical and experimental settings. To better understand these effects and their pathological mechanisms, we conducted a systematic literature search of published studies and employed a qualitative, analytical approach to identify and synthesize key findings from peer-reviewed studies, including large-scale retrospective clinical cohorts, human autopsy reports, animal models (murine, non-human primate), and in vitro brain organoid systems. While viral components were detected in post mortem central nervous system tissues, COVID-19 neuropathology appears to stem primarily from immune-mediated inflammation and vascular injury rather than direct CNS infection. Persistent glial activation and BBB disruption may underlie the long-term neurological symptoms reported in long COVID-19. Although animal models offer mechanistic insight, species-specific differences necessitate cautious extrapolation to human pathology. Further investigation into the chronic effects of SARS-CoV-2 on the brain is essential to guide long-term clinical management and therapeutic development.},
}

Humans
*COVID-19/complications/pathology/virology
Animals
*SARS-CoV-2/pathogenicity
Disease Models, Animal
Brain/virology/pathology
*Nervous System Diseases/virology/pathology/etiology
Central Nervous System/virology/pathology

@article {pmid41305428,
year = {2025},
author = {Chiang, KC and Chiu, CEN and Altaf, M and Cheng, MTK and Gupta, RK},
title = {Mechanisms of Cell-Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/v17111405},
pmid = {41305428},
issn = {1999-4915},
mesh = {Humans ; *SARS-CoV-2/immunology/physiology/pathogenicity/genetics ; *COVID-19/transmission/immunology/virology ; *Immune Evasion ; Cell Fusion ; *Virus Internalization ; Giant Cells/virology ; Animals ; Antibodies, Neutralizing/immunology ; },
abstract = {Early studies on the evolution of SARS-CoV-2 revealed mutations that favored host transmission of the virus and more efficient viral entry. However, cell-free virus spread is vulnerable to host-neutralizing antibodies. As population immunity developed, mutations that confer escape from neutralization were selected. Notably, cell syncytia formation wherein an infected cell fuses with a noninfected cell is a more efficient route of transmission that bypasses humoral immunity. Cell syncytia formation has been implicated in the pathogenicity of SARS-CoV-2 infection whilst compromising host transmission due to impaired whole virion release. Therefore, understanding the mechanisms of virus-mediated cell-cell fusion will aid in identifying and targeting more pathogenic strains of SARS-CoV-2. Whilst the general kinetics of cell-cell fusion have been known for decades, the specific mechanisms by which SARS-CoV-2 induces fusion are beginning to be elucidated. This is partially due to emergence of more reliable, high throughput methods of quantifying and comparing fusion efficiency in experimental models. Moreover, the ongoing inflammatory response and emerging health burden of long COVID may point to cell-cell fusion in the pathogenesis. In this review, we synthesize current understanding of SARS-CoV-2-mediated cell-cell fusion and its consequences on immune escape, viral persistence, and the innate immune response.},
}

Humans
*SARS-CoV-2/immunology/physiology/pathogenicity/genetics
*COVID-19/transmission/immunology/virology
*Immune Evasion
Cell Fusion
*Virus Internalization
Giant Cells/virology
Animals
Antibodies, Neutralizing/immunology

@article {pmid41304297,
year = {2025},
author = {An, M and Dong, X and Gao, Y and Ouyang, J and Ding, H and Zhu, Z and Bao, L and Feng, Y and Tian, W and Wang, P and Han, X and Shang, H},
title = {Immune Suppression, Preexisting Immunity, and Mutation Tendency Shaped SARS-CoV-2 Evolution in Persistent Infection.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112613},
pmid = {41304297},
issn = {2076-2607},
support = {2023YFC3041500//the National Key Research and Development Program of China/ ; 2023-PT320-01//the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; },
abstract = {SARS-CoV-2 evolution in persistent infection, which may induce long COVID-19, is predominantly manifested in immunocompromised hosts, who act as the viral reservoirs for future outbreaks. Therefore, understanding the evolutionary mechanisms of novel variants that can evade preexisting immune responses is critical to guide public health measures and develop vaccines tailored for vulnerable populations. We used next-generation sequencing and phylogenetic methods to delineate the evolutionary and mutational profiles of SARS-CoV-2 variants using serial oropharyngeal swab samples from 5 individuals with persistent infections. Our results revealed that the intra-host evolutionary patterns of different variants varied significantly, and the evolutionary rate in 3 immunocompromised hosts was 20 times higher than in 2 other patients. These variations likely stem from differences in immune suppression status, the strength of preexisting immune responses, and the extent of error-generating mutations. There were 15 intra-host single-nucleotide variants (iSNVs) in the spike gene among at least two variants, suggesting convergent evolution. Although most new iSNVs do not reach fixation, some of them belong to lineage-defined mutations in variants of concern (VOCs) and recent variants of interest (VOIs). The observations indicate that persistent infections serve as sources for novel, potentially harmful variants, whereas the viral evolutionary dynamics are impacted by virological, immunological, and genetic factors. Thus, there is an urgent need for individualized monitoring and management of immunocompromised hosts to prevent outbreaks caused by the viral seeds generated from them and to study viral factors associated with post-acute COVID-19 sequelae.},
}

@article {pmid41304256,
year = {2025},
author = {Mateescu, DM and Ilie, AC and Cotet, I and Guse, C and Muresan, CO and Pah, AM and Badalica-Petrescu, M and Iurciuc, S and Craciun, ML and Avram, A and Margan, MM and Enache, A},
title = {Gut Microbiome Dysbiosis in COVID-19: A Systematic Review and Meta-Analysis of Diversity Indices, Taxa Alterations, and Mortality Risk.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112570},
pmid = {41304256},
issn = {2076-2607},
support = {"Victor Babes" University of Medicine and Pharmacy Timisoara//"Victor Babes" University of Medicine and Pharmacy Timisoara/ ; },
abstract = {COVID-19 is associated with gut microbiome alterations that may influence disease outcomes through immune and inflammatory pathways. This systematic review and meta-analysis evaluated global evidence on gut dysbiosis in COVID-19. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to 5 October 2025 (PROSPERO CRD420251160970). Alpha-diversity indices and microbial taxa log-fold changes (logFC) were analyzed using random-effects models. The pooled standardized mean difference (SMD) for the Shannon index was -0.69 (95% CI -0.84 to -0.54; I[2] = 42%), confirming reduced microbial diversity. Faecalibacterium prausnitzii showed a significant pooled depletion (logFC = -1.24; 95% CI -1.68 to -0.80; k = 10; I[2] = 74%), while Enterococcus spp. was increased (logFC = 1.45; 95% CI 1.12-1.78). Egger's test did not suggest publication bias (p = 0.32). Gut dysbiosis was consistently associated with reduced microbial diversity and enrichment of pathogenic taxa, correlating with increased disease severity and mortality (HR = 1.67). These findings highlight the potential of microbiome profiling as a prognostic tool in COVID-19, although clinical translation requires further validation.},
}

@article {pmid41304215,
year = {2025},
author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV},
title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112529},
pmid = {41304215},
issn = {2076-2607},
support = {DPI/BCE nº 01/2025//University of Brasilia/ ; FAPDF nº 09/2023//Fundação de Apoio à Pesquisa do Distrito Federal/ ; },
abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.},
}

@article {pmid41303228,
year = {2025},
author = {Al-Zamil, M and Kulikova, NG and Zalozhnev, DM and Shnayder, NA and Petrova, MM and Garganeeva, NP and Zhukova, NG and Tutinina, OV and Naprienko, MV and Smekalkina, LV},
title = {Using the International Index of Erectile Function-15 in Comparative Analysis Between Transcutaneous Electrical Nerve Stimulation of the Pudendal Nerve and Low-Level Laser Therapy in the Treatment of Erectile Dysfunction After COVID-19.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14228193},
pmid = {41303228},
issn = {2077-0383},
abstract = {Background: Erectile dysfunction (ED) is one of the manifestations of long COVID-19 and in most cases has an endothelial and neurogenic nature. Many experimental and clinical investigations have revealed the high efficacy of transcutaneous electrical nerve stimulation (TENS) of the pudendal nerve and low-level laser therapy (LLLT) in the treatment of ED. Purpose: To compare LLLT and TENS, and investigate the dynamics of their efficacy when combined in the treatment of patients with post-COVID-19 ED using the International Index of Erectile Function-15 (IIEF-15). Materials and Methods: This interventional, randomized controlled trial enrolled 82 patients with ED following COVID-19. All patients had their first ED diagnosis after COVID-19 within one month of the onset of respiratory symptoms. The duration of patients' ED was not less than six months, but less than one year. Patients were divided into four groups, one of which received sham LLLT and TENS (n = 20). The remaining patients underwent effective treatment using LLLT (n = 21), TENS (n = 21), and combined LLLT and TENS (n = 20). To study the effectiveness of the treatment, IIEF-15 and an assessment of tactile sensation in the genital area before and after the treatment, as well as 3 months after the end of the treatment, were used. Results: Both LLLT and TENS had a significant effect in improving erectile function, of 38% (p ≤ 0.01) and 27% (p ≤ 0.01), respectively. The improvement in erectile function after LLLT was higher than after TENS by 8.2% (p ≤ 0.05), but the combination of these methods exceeds the result of using LLLT alone by 20% (p ≤ 0.01). The reduction in hypoesthesia after LLLT did not exceed 17.4% (p ≤ 0.05). However, after TENS, the reduction in hypoesthesia reached 48.7% (p ≤ 0.01), and with a combination of the two methods, it reached 60.9% (p ≤ 0.01). Treatment outcomes in LLLT, TENS, and LLLT + TENS groups were stable for 3 months. Conclusions: According to IIEF-15 dynamics, LLLT and TENS are both very beneficial in treatment of post-COVID-19 ED, with LLLT showing a moderately better outcome than TENS. LLLT and TENS were found to have significant positive therapeutic effects on orgasm, sexual desire, and sexual satisfaction, among other aspects of sexual function. Nevertheless, the combination of LLLT and TENS proved to be much more successful in enhancing all IIEF domains, expanding the therapeutic effect spectrum, and improving the TENS effect following LLLT application. Only after TENS did genital hypoesthesia reliably regress, and the effect was amplified when TENS and LLLT were combined.},
}

@article {pmid41303176,
year = {2025},
author = {Olarinde, F and Nunes-Silva, A and Sanchez-Ramirez, DC and Molgat-Seon, Y and Villar, R},
title = {Using Active Standing Orthostatic Stress Test to Assess Physiological Responses in Individuals with Long COVID: A Systematic Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14228139},
pmid = {41303176},
issn = {2077-0383},
abstract = {Background/Objectives: Individuals experiencing long COVID (LC) frequently report orthostatic intolerance symptoms, which may be linked to autonomic and cardiovascular dysfunction. The active standing test provides a simple, clinically relevant means to assess these impairments. This systematic review aims to determine the use of the active standing orthostatic stress test in evaluating cardiovascular, autonomic, and respiratory responses in people experiencing LC. Methods: A systematic search, according to PRISMA guidelines, was conducted in PubMed, MEDLINE, EMBASE, CINAHL, and Scopus for articles published between 2020 and 2025. This study was registered in PROSPERO CRD-42024615872. Studies were included if they used the active standing test, enrolled adults (≥18 years), included both long COVID and healthy control groups, used continuous beat-to-beat measurements, and reported physiological outcomes. Risk of bias was assessed using the nine-point Newcastle-Ottawa Scale. Results: Three studies (216 participants experiencing LC and 186 controls) met the inclusion criteria. Across studies, LC individuals consistently exhibited elevated heart rate in both supine and standing positions. However, blood pressure findings were more variable: only one study reported 13% of participants met orthostatic hypotension criteria, while another found significant increases in diastolic blood pressure during standing. Long COVID groups also showed reduced heart rate variability compared to controls. Conclusions: Individuals experiencing LC show elevated heart rate and impaired autonomic function during active standing, with subgroup-specific blood pressure changes. These alterations may contribute to dizziness, fatigue, and reduced activity tolerance. Incorporating active standing into clinical assessment could aid early identification of autonomic dysfunction and inform rehabilitation strategies, though more research is urgently needed.},
}

@article {pmid41302967,
year = {2025},
author = {Alghamdi, F and Meertens, R and Obotiba, AD and Harries, LW and Appleby, S and Mokbel, K and Knapp, KM and Strain, WD},
title = {Assessment of Health-Related Quality of Life and Biomarkers in Long COVID: A 12-Month Longitudinal Feasibility Cohort.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14227931},
pmid = {41302967},
issn = {2077-0383},
support = {part of PhD project//Qassim University/ ; },
abstract = {Background/Objectives: Long COVID (LC) causes persistent symptoms, including fatigue, musculoskeletal (MSK) pain, and a lower quality of life. It is hypothesised that chronic low-grade inflammation in LC could impact bone, joints, and muscle microcirculation, but evidence is limited. Our aim is to assess health-related quality of life (HRQoL) and circulating inflammation, bone turnover markers (BTM), and vitamin D in LC individuals to explore their potential association with MSK function. Methods: Prospective longitudinal cohort; LC n = 45, well-recovered (WR) n = 40; 12 ± 2 months follow-up. Baseline and follow-up assessments included evaluations of HRQoL and pain-rating questionnaires, and blood analysis of inflammatory and bone turnover markers (BTM). Results: More females were in the LC group. LC reported significantly lower HRQoL compared to WR, with no change over 12 months. LC had higher vitamin D levels at baseline, median 29.46 ng/mL (23.75; 35.06) compared to WR 20.36 ng/mL (15.995; 27.65) (p = 0.0021). Both groups experienced significant increases in vitamin D after 12 months: WR median from 21.4 ng/mL (16.34; 27.89) to 29.58 ng/mL (25.33; 41.74), (p =< 0.001) and LC median from 32.695 ng/mL (23.665; 35.1) to 35.89 ng/mL (30.1; 41.2), (p = 0.0023). Pain rating showed LC also experienced more hand pain at baseline median 1 (0; 5), (p = 0.003). There were no differences between groups in BTM or cytokines over time. Conclusions: This feasibility cohort showed that LC is associated with a reduction in HRQoL and joint symptoms; however, no significant changes were observed in the inflammatory markers, indicating the need for ongoing monitoring. Future studies should explore MSK, muscle function via imaging, and ways to enhance musculoskeletal health and well-being.},
}

@article {pmid41302639,
year = {2025},
author = {Perestiuk, V and Sverstyuk, A and Kosovska, T and Volianska, L and Boyarchuk, O},
title = {A Predictive Model for the Development of Long COVID in Children.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
doi = {10.3390/ijerph22111693},
pmid = {41302639},
issn = {1660-4601},
support = {0123U100301//Ministry of Health of Ukraine/ ; },
mesh = {Humans ; Child ; *COVID-19/epidemiology/complications ; Child, Preschool ; Infant ; Male ; Female ; Adolescent ; Cross-Sectional Studies ; Risk Factors ; SARS-CoV-2 ; *Models, Theoretical ; },
abstract = {BACKGROUND/OBJECTIVES: Machine learning is an extremely important issue, considering the potential to prevent the onset of long-term complications from coronavirus disease or to ensure timely detection and effective treatment. The aim of our study was to develop an algorithm and mathematical model to predict the risk of developing long COVID in children who have had acute SARS-CoV-2 viral infection, taking into account a wide range of demographic, clinical, and laboratory parameters.

METHODS: We conducted a cross-sectional study involving 305 pediatric patients aged from 1 month to 18 years who had recovered from acute SARS-CoV-2 infection. To perform a detailed analysis of the factors influencing the development of long-term consequences of coronavirus disease in children, two models were created. The first model included basic demographic and clinical characteristics of the acute SARS-CoV-2 infection, as well as serum levels of vitamin D and zinc for all patients from both groups. The second model, in addition to the aforementioned parameters, also incorporated laboratory test results and included only hospitalized patients.

RESULTS: Among 265 children, 138 patients (52.0%) developed long COVID, and the remaining 127 (48.0%) fully recovered. We included 36 risk factors of developing long COVID in children (DLCC) in model 1, including non-hospitalized patients, and 58 predictors in model 2, excluding them. These included demographic characteristics of the children, major comorbid conditions, main symptoms and course of acute SARS-CoV-2 infection, and main parameters of complete blood count and coagulation profile. In the first model, which accounted for non-hospitalized patients, multivariate regression analysis identified obesity, a history of allergic disorders, and serum vitamin D deficiency as significant predictors of long COVID development. In the second model, limited to hospitalized patients, significant risk factors for long-term sequelae of acute SARS-CoV-2 infection included fever and the presence of ≥3 symptoms during the acute phase, a history of allergic conditions, thrombocytosis, neutrophilia, and altered prothrombin time, as determined by multivariate regression analysis. To assess the acceptability of the model as a whole, an ANOVA analysis was performed. Based on this method, it can be concluded that the model for predicting the risk of developing long COVID in children is highly acceptable, since the significance level is p < 0.001, and the model itself will perform better than a simple prediction using average values.

CONCLUSIONS: The results of multivariate regression analysis demonstrated that the presence of a burdened comorbid background-specifically obesity and allergic pathology-fever during the acute phase of the disease or the presence of three or more symptoms, as well as laboratory abnormalities including thrombocytosis, neutrophilia, alterations in prothrombin time (either shortened or prolonged), and reduced serum vitamin D levels, are predictors of long COVID development among pediatric patients.},
}

Humans
Child
*COVID-19/epidemiology/complications
Child, Preschool
Infant
Male
Female
Adolescent
Cross-Sectional Studies
Risk Factors
SARS-CoV-2
*Models, Theoretical

@article {pmid41302566,
year = {2025},
author = {Sui, SX and Yu, L},
title = {Patient and Professional Perspectives on Long COVID: A Systematic Literature Review and Meta-Synthesis.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
doi = {10.3390/ijerph22111620},
pmid = {41302566},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/psychology ; *Health Personnel/psychology ; SARS-CoV-2 ; Qualitative Research ; },
abstract = {BACKGROUND: Post-COVID-19 condition ('long COVID') involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, recovery, and service use. We synthesised perspectives from people living with long COVID and healthcare professionals to inform service design and policy.

METHODS: We conducted a systematic review and qualitative meta-synthesis. MEDLINE, Embase, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies published between 1 January 2020 and 19 August 2025. Eligible studies reported qualitative data from adults with long COVID (≥12 weeks after acute infection) and/or healthcare professionals in any setting. We excluded non-qualitative, non-primary, or non-English reports. Two reviewers independently screened, extracted, and appraised studies using the Critical Appraisal Skills Programme checklist. Data were synthesised thematically. The protocol was registered with the Open Science Framework.

FINDINGS: Of 1544 records screened, 49 studies met the inclusion criteria: 41 involving patients, two involving professionals, and six involving both. Eight patient themes (including symptom burden, identity disruption and stigma) and four professional themes (including recognition, care coordination and holistic care models) were identified. Recognition emerged as a cross-cutting mechanism: validation and consistent pacing guidance facilitated engagement and safer activity, whereas invalidation and inconsistent advice were associated with distress, avoidance, and disengagement. Trajectories showed gradual expansion of multidisciplinary care models, but major capacity and equity gaps persisted. Most studies had low methodological concerns, although heterogeneity in populations and settings was substantial.

INTERPRETATION: Long COVID is a chronic, biological condition that also intersects with social and psychological dimensions, and may present with episodic, continuous, or progressive trajectories. Healthcare services must prioritise early validation, provide consistent pacing and relapse prevention guidance, expand access to multidisciplinary and peer-supported rehabilitation, integrate mental healthcare, strengthen coordinated pathways, and support graded return to work. Explicit attention to equity is required to avoid widening disparities.},
}

Humans
*COVID-19/psychology
*Health Personnel/psychology
SARS-CoV-2
Qualitative Research

@article {pmid41301920,
year = {2025},
author = {Knauer, TS and Mardin, CY and Rech, J and Michelson, G and Stog, A and Zott, J and Steußloff, F and Güttes, M and Sarmiento, H and Ilgner, M and Jakobi, M and Hohberger, B and Schottenhamml, J},
title = {Evaluation of Stereopsis Performance, Gaze Direction and Pupil Diameter in Post-COVID Syndrome Using Machine Learning.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112828},
pmid = {41301920},
issn = {2227-9059},
support = {2490-PC-2021-V14//Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit/ ; GRK 2504/1//Deutsche Forschungsgemeinschaft/ ; 01EO2105//Bundesministerium für Forschung, Technologie und Raumfahrt/ ; },
abstract = {Background/Objectives: Post-COVID syndrome (PCS) encompasses symptoms that persist for at least 12 weeks after the onset of a COVID-19 infection and cannot be explained by other causes. The most common symptoms are fatigue, cognitive impairments, and physical limitations. The objective diagnosis of PCS is still challenging, as specific biomarkers are lacking. One possibility to measure cognitive impairment is the virtual-reality-oculomotor-test-system (VR-OTS, Talkingeyes & More, Germany). It shows stereoscopic stimuli in a VR-environment to the test person. While working on the visual tasks, many features are recorded. These features can be categorized into three groups: stereopsis performance, gaze direction, and pupil diameter. The aim of this study was to investigate which of these three feature groups is best to distinguish patients with PCS from a healthy control group. Methods: In total, 429 patients with PCS were recruited within the disCOVer 1.0 and disCOVer 2.0 study at the Department of Ophthalmology, Universitätsklinikum (Erlangen, Germany). All patients received VR-OTS measurements. From these measurements, a total of 95 features were extracted, which can be categorized into three groups: gaze direction, pupil diameter, and stereopsis performance. In the first step, support vector machines (SVMs) were trained on these different feature sets and evaluated using the area under receiver operating characteristic (AUROC) as the evaluation metric. In the second step, the same procedure was repeated with each feature independently to investigate which were most the predictive per group. Results: The SVM using the pupil diameter features yielded an AUROC of 0.73, the one using the gaze direction features resulted in an AUROC of 0.68. and the stereopsis performance features produced an AUROC of 0.66. The SVM using all VR-OTS data showed an AUROC of 0.68. For the single features, the index of pupillary activity (IPA) showed the best discrimination. Moreover, all features that were evaluated at different difficulties showed the same pattern-that the more difficult test proved to be more predictive. Conclusions: The study showed that VR-OTS can distinguish between patients with PCS and healthy control probands. Since different features showed a better performance than others, it makes sense for further studies to use a subset of the available features for further analysis.},
}

@article {pmid41301889,
year = {2025},
author = {Ivanovska, M and Homadi, MS and Angelova, G and Taskov, H and Murdjeva, M},
title = {Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112797},
pmid = {41301889},
issn = {2227-9059},
abstract = {Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.},
}

@article {pmid41301758,
year = {2025},
author = {García-Onrubia, J and Vazirani, R and Feltes, G and Sánchez-Del Hoyo, R and Viana-Llamas, MC and Raposeiras-Roubín, S and Romero, R and Alfonso-Rodríguez, E and Uribarri, A and Santoro, F and Becerra-Muñoz, V and Pepe, M and Castro-Mejía, AF and Signes-Costa, J and Gonzalez, A and Marín, F and Lopez-País, J and Cerrato, E and Vázquez-Cancela, O and Espejo-Paeres, C and López Masjuan, Á and Velicki, L and El-Battrawy, I and Ramakrishna, H and Fernandez-Ortiz, A and Nuñez-Gil, IJ},
title = {The Long-Term Outcomes of Corticosteroid Use in COVID-19 Patients with Cardiovascular Disease: A Propensity-Matched Analysis from the Multi-Center International Prospective Registry (HOPE-2).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112665},
pmid = {41301758},
issn = {2227-9059},
abstract = {Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4-14] and 11 days [IQR: 7-18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients.},
}

@article {pmid41301729,
year = {2025},
author = {Quach, TC and Wilson, A and Sum-Ping, O and Lomba, S and Geng, LN and Shafer, R and Miglis, MG and Yang, PC and Grossman, L and Ricciardiello, G and Bonilla, H},
title = {Can Low Cortisol Predict Long COVID? A Controversial Issue.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112636},
pmid = {41301729},
issn = {2227-9059},
abstract = {Cortisol dysregulation has been proposed as a biomarker of long COVID (LC), but findings remain inconsistent. Prior reports suggested low cortisol levels in LC, yet collection times and study designs varied substantially. To evaluate morning serum cortisol distributions in an independent LC cohort, accounting for circadian timing and sleep patterns, we performed a retrospective cross-sectional study of consecutive adults seen at the Stanford Long COVID Clinic between 14 February 2022 and 31 July 2024 (IRB #62996). Eligible participants had confirmed SARS-CoV-2 infection, symptoms persisting ≥3 months per NASEM criteria, completion of the Alliance Sleep Questionnaire (ASQ), and a morning serum cortisol measured using the Roche Elecsys[®] Cortisol II assay. Analyses were restricted to collections between 05:00-10:00, categorized as early morning peak (EMP: 05:00-08:00) or mid-morning (MMP: 08:01-10:00). Cortisol was classified as low (<6.2 μg/dL), normal (6.2-19.4 μg/dL), or elevated (>19.4 μg/dL). Among 86 LC patients (69.8% female; mean age 45.4 ± 12.9 years), the mean serum cortisol level was 15.67 ± 6.76 μg/dL. Overall, 62.8% of patients had cortisol within the reference range, 36.0% had elevated levels, and only 1.2% (n = 1) had a low value. Cortisol distributions were comparable across the EMP and MMP collection windows, with no statistically significant differences observed by sleep alignment. Inflammatory markers, including CRP and D-dimer, were largely within reference ranges across all cortisol strata. Contrary to earlier reports, low morning cortisol was rare in this LC cohort; most values were normal or elevated. Findings underscore the importance of circadian timing when interpreting cortisol in LC and highlight the need for prospective studies with serial measurements to determine biomarker utility.},
}

@article {pmid41300187,
year = {2025},
author = {Pour Mohammadi, S and Etesamipour, R and Mercado Romero, F and Noroozi Fashkhami, M and Peláez, I},
title = {Physical Symptoms and Neurocognitive Complaints in Long COVID: Associations with Gender, Age, Education, and Clinical Factors.},
journal = {Brain sciences},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/brainsci15111180},
pmid = {41300187},
issn = {2076-3425},
abstract = {Long COVID is frequently accompanied by neurocognitive complaints, yet the combined effects of demographic and clinical factors remain unclear. This study examined individuals six months after their most recent SARS-CoV-2 infection using a Demographic/Infection-History form, a Physical and Neurocognitive Symptom Checklist (binary), and the Post-COVID Cognitive Impairment Scale (memory, attention; 5-point Likert). Participants were recruited through convenience sampling from multiple community and online sources. Inclusion criteria required confirmed prior COVID-19 infection, self-perceived or clinically documented Long COVID symptoms, and no history of neurological or severe psychiatric disorders. The final sample consisted of 212 participants (mean age = 39.7 years, SD = 10.5), of whom 67.9% were female, and most held a master's (35.4%) or bachelor's (28.3%) degree. Difficulties with retaining new information (57.8%) and concentrating (52.1%) were the most frequent neurocognitive complaints, while severe fatigue after mild activity (23.2%) and chronic fatigue (22.7%) were the most common physical symptoms. Confusion and decision-making difficulty were more frequent among younger participants; women reported greater difficulty retaining new information, and difficulty concentrating varied by education level. A multivariable regression model explained 7% of the variance in total cognitive complaints, identifying education level (β = -0.18, p < 0.01) and number of physical symptoms (β = 0.19, p < 0.01) as significant predictors. Higher educational attainment was associated with fewer cognitive complaints, whereas a greater burden of physical symptoms predicted higher complaint scores. Persistent cognitive difficulties in Long COVID appear closely related to physical symptom burden and protective factors such as education, rather than to infection frequency or sensory dysfunction duration. Findings highlight the need for routine cognitive screening, fatigue-focused management, and longitudinal multimodal research to elucidate underlying mechanisms and recovery pathways.},
}

@article {pmid41299665,
year = {2025},
author = {Dalle Carbonare, L and Minoia, A and Zouari, S and Braggio, M and Cominacini, M and Gaglio, SC and Piritore, FC and Lorenzi, P and Meneghel, M and Dervishi, K and Corsi, A and Pedrinolla, A and Giuriato, G and Fiore, A and Celesia, A and Guerricchio, L and Venturelli, M and Schena, F and Donadelli, M and Mottes, M and Romanelli, MG and Perduca, M and Guardavaccaro, D and Crisafulli, E and Zipeto, D and Barile, L and Valenti, MT},
title = {Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {508},
pmid = {41299665},
issn = {1478-811X},
support = {Excellence Project 2023-2027 of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona//MUR/ ; PRIN 2022 - Projects of Relevant National Interest, funded by the European Union - NextGenerationEU, PNRR, Mission 4, Component 2, Investment 1.1, project Title "Fine definition of systemic and mucosal response in SARS-CoV-2 vaccinated subjects" - CUP code B53D23003410006.//MUR/ ; },
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *MicroRNAs/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism ; *COVID-19/metabolism/pathology ; *Core Binding Factor Alpha 1 Subunit/metabolism/genetics ; Human Umbilical Vein Endothelial Cells/metabolism ; Signal Transduction ; SARS-CoV-2 ; Female ; Male ; Mesenchymal Stem Cells/metabolism ; Stress, Physiological ; },
abstract = {BACKGROUND: Subjects with Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), experience a wide range of symptoms, including fatigue and respiratory disturbances, affecting their quality of life. Despite the increasing prevalence of Long COVID, the underlying pathogenic mechanisms remain poorly understood. Extracellular vesicles (EVs) are known to be involved in various processes, such as tissue repair and the transmission of viral particles. However, the specific characteristics and functional roles of EVs derived- from patients with Long COVID (LC-EVs) are poorly characterized.

METHODS: To uncover systemic mechanisms underlying Long COVID, we performed a comprehensive characterization of patient-derived extracellular vesicles (EVs) via Nanoparticle Tracking analysis (NTA), Atomic Force Microscopy (AFM), Transmission Electron Microscope (TEM) and flow cytometry. These EVs were applied to lung cells, Mesenchymal Stem Cell (MSCs), Human Umbilical Vein Endothelial Cells (HUVECs) and Aortic Smooth Muscle Cells (ASMCs), revealing stress responses through SESN1, SESN2, and p53 activation. We further assessed mitochondrial respiration to evaluate metabolic dysfunction, and conducted targeted transfection experiments to dissect the molecular pathways involved, shedding light on EV-driven cellular reprogramming.

RESULTS: Thus, we observed that Long COVID (LC) patients experienced breathlessness and leg discomfort during exertion. Our data highlighted that LC-EVs induce aberrant RUNX2 expression and activate the p53/p21 pathway in lung cells as well stress responses. Additionally, LC-EVs impair mitochondrial function and cellular adaptability under metabolic stress, reducing maximal respiration and ATP production at high cell densities. Protein interaction analysis showed RUNX2 involvement in key biological processes and post-transcriptional regulation by hsa-miR-204-5p was identified. Finally, LC-EVs also activated stress pathways and increased RUNX2, SESN, p53, and p21 levels in endothelial cells, aortic smooth muscle cells, and mesenchymal stem cells.

CONCLUSIONS: In conclusions, these findings provide new insights into the role of extracellular vesicles in Long COVID, revealing their involvement in cellular stress and impaired mitochondrial function.},
}

Humans
*Extracellular Vesicles/metabolism
*MicroRNAs/metabolism/genetics
*Tumor Suppressor Protein p53/metabolism
*COVID-19/metabolism/pathology
*Core Binding Factor Alpha 1 Subunit/metabolism/genetics
Human Umbilical Vein Endothelial Cells/metabolism
Signal Transduction
SARS-CoV-2
Female
Male
Mesenchymal Stem Cells/metabolism
Stress, Physiological

@article {pmid41299639,
year = {2025},
author = {Gamillscheg-Müllner, P and Łaszewska, A and Hoffmann, K and Simon, J and Mayer, S},
title = {Barriers, facilitators, and the role of central coordination: understanding long COVID-19 healthcare access in a universal healthcare system.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {286},
pmid = {41299639},
issn = {0778-7367},
support = {SO68900010//Medical University of Vienna and the University of Vienna/ ; SO68900010//Medical University of Vienna and the University of Vienna/ ; SO68900010//Medical University of Vienna and the University of Vienna/ ; },
}

@article {pmid41295749,
year = {2025},
author = {Westman, H and Hammarström, P and Nyström, S},
title = {SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00550},
pmid = {41295749},
issn = {1520-4995},
abstract = {Long COVID, or postacute sequelae of COVID-19 from SARS-CoV-2 infection, is a persistent debilitating disease affecting multiple systems and organs. Long COVID pathophysiology is a complex and not fully established process. One prevailing theory is that the formation of fibrin amyloid microclots (fibrinaloids), due to SARS-CoV-2 infection, can induce persistent inflammation and capillary blockage. An association between the amyloidogenic Spike protein of SARS-CoV-2 and impaired fibrinolysis was made when it was observed that fibrin clots formed in the presence of a mixture of amyloid fibrils from the spike protein mediated resistance to plasmin lysis. Here, we use purified components from the coagulation cascade to investigate the molecular processes of impaired fibrinolysis using seven amyloidogenic SARS-COV-2 Spike peptides. Five of seven Spike amyloid fibrils appeared not to substantially interfere with the fibrinogen-fibrin-fibrinolysis process in vitro, while two spike fibrils were active in different ways. Spike601 amyloid fibrils (sequence 601-620) impaired thrombin-mediated fibrin formation by binding and sequestering fibrinogen but did not affect fibrinolysis. On the contrary, fibrin clots formed in the presence of Spike685 amyloid fibrils (sequence 685-701) exhibited a marked resistance to plasmin-mediated fibrinolysis. We conclude that Spike685 amyloid fibrils can induce dense fibrin clot networks as well as incorporate fibrin into aggregated structures that resist fibrinolysis. Our study proposes a molecular mechanism for how the Spike protein of SARS-CoV-2 could contribute to the formation of fibrinolysis-resistant microclots observed in long COVID.},
}

@article {pmid41293716,
year = {2025},
author = {Mancini, DM and Brunjes, DL and Cook, D and Soto, T and Blate, M and Quan, P and Yamazaki, T and Norweg, A and Natelson, BH},
title = {Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1669036},
pmid = {41293716},
issn = {2296-858X},
abstract = {INTRODUCTION: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience symptoms of fatigue, dyspnea, mental fog, and worsening fatigue after physical or mental efforts. Some of these patients have been found to hyperventilate. In long COVID patients, many of whom also have ME/CFS, dysfunctional breathing (DB) has been described. Whether patients with ME/CFS, independent of COVID-19, experience dysfunctional breathing is unknown, as well as how it may relate to hyperventilation.

METHODS: We performed serial 2-day cardiopulmonary exercise testing (CPET) in 57 patients with ME/CFS and 25 age- and activity-matched control participants. Peak oxygen consumption (VO2), ventilatory efficiency slope (VE/VCO2), O2 saturation, end-tidal CO2 (PetCO2), heart rate, and mean arterial blood pressure were measured in all patients during upright incremental bicycle exercise. Ventilatory patterns were reviewed using minute ventilation (VE) versus time, respiratory rate, and tidal volume versus minute ventilation graphs. Chronic hyperventilation (HV) was defined as a PETCO2 of <34 mm Hg that persisted during low-intensity exercise. Dysfunctional breathing was characterized by a 15% increase in oscillations in minute ventilation during at least 60% of the exercise duration or by a scatterplot pattern of respiratory rate and tidal volume plotted versus minute ventilation.

RESULTS: The patients with ME/CFS had an average age of 38.6 ± 9.6 years, and a mean body mass index (BMI) of 24.1 ± 3.4, which was comparable to the sedentary controls. All participants performed maximal exercise, achieving a respiratory exchange ratio (RER) of >1.05. For the patients with ME/CFS, peak VO2 averaged 22.3 ± 5.3 mL/kg/min, which was 79 ± 20% of predicted and comparable to that observed in the sedentary controls (23.4 ± 4.6 mL/kg/min; 81 ± 12%; p = NS). A total of 24 patients with ME/CFS (42.1%) met the criteria for dysfunctional breathing compared to four sedentary controls (16%) (p < 0.02). In total, 18 patients with ME/CFS (32%) had hyperventilation compared to one sedentary control participant (4%) (p < 0.01), and nine patients with ME/CFS had both hyperventilation and dysfunctional breathing, whereas no sedentary participant exhibited both. The patients with ME/CFS and hyperventilation had significantly higher VE/VCO2 ratios (HV+: 34.7 ± 7.2; HV-: 28.1 ± 3.8; p < 0.001). A total of 15 of 18 patients with hyperventilation (83%) had either elevated VE /VCO2 ratios (n = 15) or dysfunctional breathing (n = 9) compared to 44% (n = 17) of the 40 non-hyperventilators (p < 0.01).

CONCLUSION: Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.},
}

@article {pmid41293426,
year = {2025},
author = {Sørensen, L and Agergaard, J and Nielsen, TB and Schiøttz-Christensen, B and Laursen, CH and Leth, S and Nielsen, CV and Oestergaard, LG},
title = {Construct validity of self-reported and interview-guided administration methods of the Danish version of the post-COVID-19 functional Status scale.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1690892},
pmid = {41293426},
issn = {2673-6861},
abstract = {INTRODUCTION: The Post-COVID-19 Functional Status (PCFS) scale was quickly adopted into COVID-19 research and clinical practice worldwide to monitor functional status and recovery. The scale has been translated into Danish, and three different administration methods have been employed. However, clinicians have expressed concerns about the scale's ability to capture work-related functional limitations. Therefore, the purpose of this study was to evaluate the construct validity of three different administration methods of the Danish version of the PCFS scale.

METHODS: This cross-sectional study included patients with long COVID who completed three versions of the PCFS scale: a questionnaire-based version, a flowchart-based version, and an interview-based version. The construct validity was evaluated following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines by testing predefined hypotheses that compared the PCFS scale with sick leave and EuroQoL Five-dimensions Five level (EQ-5D-5l).

RESULTS: A total of 437 patients, with a mean age 48 years, 75% female, and 59% on sick leave, were included in this study. Statistically significant differences between the three administration methods were found. Of the 234 patients on sick leave, only 50%-54% had a PCFS grade ≥3 which was below our predefined hypothesis. Furthermore, correlations between the PCFS scale and EQ-5D-5l was lower than hypothesized.

CONCLUSION: None of the three administration methods effectively captured work-related functional limitations associated with being on part-time or full-time sick leave. Additionally, correlations with quality of life were lower than expected. Overall, the construct validity of the PCFS scale was only partially supported.},
}

@article {pmid41291987,
year = {2025},
author = {Rhodes, S and Tutbury, M},
title = {Suggestions for managing long Covid in primary care in Aotearoa New Zealand: a qualitative study.},
journal = {Journal of primary health care},
volume = {},
number = {},
pages = {},
doi = {10.1071/HC25143},
pmid = {41291987},
issn = {1172-6156},
abstract = {Introduction In Aotearoa New Zealand, the responsibility for management of long Covid sits with primary care. GPs are often the first point of contact for these patients in a system that is already overburdened. Globally, patient experiences of accessing support for long Covid are varied. To date, the perspectives of New Zealanders living with the condition, on how best to support their care, have not been sought. Aim The aim of this study is to explore what a long Covid service should offer from the perspectives of those living with the condition. Methods Participants were recruited via the New Zealand long haulers Facebook group and individual interviews and discussions were conducted using Zoom. These were semi-structured with a few loosely structured questions to encourage discussion. Data were analysed using Braun and Clarke's thematic analysis. Results Eighteen participants were recruited. Four themes were identified in the data: practical guidance to support the health care journey; training and collaboration between health professionals; personalised care; and opportunity for health system change. Discussion Overall, participants appeared to want interdisciplinary knowledge sharing; collaborative services with clear lines of communication and a person-centred approach to care. Many of these proposed suggestions for a long Covid clinic align with the Ministry of Health recommendations. However, to date, there is no addition support from Government to support these long Covid service recommendations.},
}

@article {pmid41286763,
year = {2025},
author = {Assavanopakun, P and Wangkawong, S and Kiratipaisarl, W and Sirikul, W and Promkutkao, T and Promkutkeo, S and Kitro, A},
title = {The hidden burden: prevalence and risk factors of long COVID among university students in Chiang Mai, Thailand.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {4123},
pmid = {41286763},
issn = {1471-2458},
support = {No.074/2566//Faculty of Medicine, Chiang Mai University/ ; },
mesh = {Humans ; Thailand/epidemiology ; Female ; *COVID-19/epidemiology ; *Students/statistics & numerical data ; Male ; Cross-Sectional Studies ; Universities ; Prevalence ; Young Adult ; Risk Factors ; Adult ; Surveys and Questionnaires ; Adolescent ; COVID-19 Vaccines/administration & dosage ; SARS-CoV-2 ; },
abstract = {BACKGROUND: As the COVID-19 pandemic transitions to an endemic phase, long COVID symptoms following SARS-CoV-2 infection have emerged as a new global health challenge. However, its impact on university students remains underexplored. This study aimed to assess the prevalence of long COVID symptoms and identify its predictive factors.

METHODS: A cross-sectional study was conducted from February to August 2023 among Thai university students in Chiang Mai. An online questionnaire collected data on demographics, COVID-19 history, vaccination, and health status. Multivariable binary logistic regression was used to identify factors associated with long COVID.

RESULTS: A total of 997 students participated (60.5% female, mean age 20.6 years). Of these, 60.9% had received at least three COVID-19 vaccine doses, and 21.4% had received more than three mRNA vaccine doses. The prevalence of long COVID symptoms was 21.9% (n = 218). Common symptoms included respiratory issues (54.6%), neurological complaints (50.4%), psychological symptoms (42.7%), and poor sleep quality (34.9%). Significant predictors of long COVID included severe initial infection (aOR = 15.3; 95% CI: 5.3-44.3; p < 0.001), longer illness duration (aOR = 1.05; 95% CI: 1.0-1.1; p = 0.031), and poor sleep quality (aOR = 2.1; 95% CI: 1.4-3.1). Each additional dose of mRNA vaccine reduced the likelihood of severe outcomes by 14% (aOR = 0.86; 95% CI: 0.8-1.0; p = 0.044).

CONCLUSION: A minority of Thai university students reported long COVID symptoms. Vaccination, especially with multiple mRNA doses, was linked to reduced risk. Early detection and targeted support during recovery may help mitigate long-term health consequences in this group.},
}

Humans
Thailand/epidemiology
Female
*COVID-19/epidemiology
*Students/statistics & numerical data
Male
Cross-Sectional Studies
Universities
Prevalence
Young Adult
Risk Factors
Adult
Surveys and Questionnaires
Adolescent
COVID-19 Vaccines/administration & dosage
SARS-CoV-2

@article {pmid41286257,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and AlArab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: lung pathophysiology and its relationship with cognitive dysfunction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-26568-y},
pmid = {41286257},
issn = {2045-2322},
support = {NIH NCATS S10OD026960, NIH CTSA program grant UM1TR004403, NIH NHLBI R01HL169765, NIH NHLBI R01HL126771/NH/NIH HHS/United States ; COVID-19 and Emerging Respiratory Viruses Research Award//American Lung Association/ ; },
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and [129]Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age = 54 ± 11 yrs.; 10 females) that were 32 ± 5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower [129]Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}

@article {pmid41285857,
year = {2025},
author = {Green, R and Marjenberg, Z and Lip, GYH and Banerjee, A and Wisnivesky, J and Delaney, BC and Peluso, MJ and Wynberg, E and Abduljawad, S},
title = {A systematic review and meta-analysis of the impact of vaccination on prevention of long COVID.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10326},
pmid = {41285857},
issn = {2041-1723},
abstract = {Long COVID affects millions worldwide and its prevention is a critical public health strategy. While prior analyses show primary vaccination prevents long COVID in subsequent infections, the effect of booster vaccination on long COVID after Omicron infections is unclear. This systematic review identifies 31 observational studies, of which 11 are suitable for pairwise meta-analyses. The pooled odds ratio (OR) of long COVID in those vaccinated (any dose) versus unvaccinated is 0.77 (95% confidence interval [CI] 0.70-0.85; p < 0.0001; 10 studies). ORs were also lower for primary course vaccination versus unvaccinated (OR 0.81; 95% CI 0.79-0.83; p < 0.0001; 3 studies), booster vaccination versus unvaccinated (OR 0.74; 95% CI 0.63-0.86; p = 0.0001; 4 studies), and booster vaccination versus primary course vaccination (OR 77; 95% CI 0.65-0.92; p = 0.0044; 3 studies). These findings indicate that booster vaccination can provide additional protection against long COVID, highlighting the importance of seasonal vaccination against new SARS-CoV-2 variants. They should, however, be interpreted cautiously, given the small number of studies and the low quality of evidence.},
}

@article {pmid41285594,
year = {2025},
author = {Lubell, J},
title = {To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!.},
journal = {Annals of family medicine},
volume = {23},
number = {6},
pages = {570-572},
doi = {10.1370/afm.240494},
pmid = {41285594},
issn = {1544-1717},
mesh = {Humans ; *Caregivers/psychology ; Female ; *Biomedical Research ; Fatigue Syndrome, Chronic/therapy/psychology ; },
abstract = {My daughter has been diagnosed with a range of chronic conditions, including Hyper-mobile Ehlers-Danlos Syndrome and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I have approached my role as caregiver in the same way I approach my day job leading social science research: reading the literature, carefully observing her condition, and developing hypotheses about her conditions and how they might be treated. I now have more than 7 years of longitudinal observation-a wealth of data-but no easy way to share with the medical research community the hypotheses these observations have engendered and my ideas about how to productively structure future research to accelerate progress toward treatments for her and others like her. In this essay, I share my thoughts on why patient and caregiver observations and hypotheses are important and how the medical research field might tap into them to make faster progress toward effective treatments for complex medical conditions.},
}

Humans
*Caregivers/psychology
Female
*Biomedical Research
Fatigue Syndrome, Chronic/therapy/psychology

@article {pmid41283027,
year = {2025},
author = {Cousins, O and Jokela-Pansini, M and Alwan, NA and Barnard, E and Dainow, J and Dalton, C and Davies, G and Faghy, MA and Gilmour, E and Patel, I and Sherwood, O and Westerhof, L and Greenhough, B},
title = {Co-creating a social science research agenda for Long Covid.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1654488},
pmid = {41283027},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/therapy ; *Social Sciences ; Surveys and Questionnaires ; Female ; Male ; *Research ; SARS-CoV-2 ; Adult ; Middle Aged ; Health Personnel ; },
abstract = {INTRODUCTION: Our objective was to understand how social scientific research could best address the needs and concerns of patients, families, carers, healthcare professionals, academics, private and public sector professionals, and volunteers from Long Covid charities and support groups and people with lived experience of Long Covid. We worked with different stakeholders to develop a list of research priorities that particularly focused on social science as this is where our collective expertise lies, but similar methods could also be used to set research priorities in the natural sciences, medicine or the humanities.

METHODS: We used purposive sampling and conducted two online surveys. The first online survey (N = 57) asked participants to identify their top five questions of concern, which resulted in a list of 253 questions. These questions were then consolidated, refined and edited down to 55 questions, categorized by topic. In the second survey (N = 66), we asked participants to select and rank their top 10 questions from this refined list. The final output was a ranked list of nine questions based on those prioritized by at least 50% of the respondents.

RESULTS: Nine research questions were developed concerning (i) treatments, therapies, and strategies; (ii) financial support; (iii) repeated reinfections; (iv) training of healthcare professionals; (v) mental health impact; (vi) future of research funding; (vii) airborne transmissions of COVID-19; (viii) developing therapeutics informed by patients' experiences; and (ix) socioeconomic impacts of Long Covid. Many of the issues raised mirror those discussed in previous work in the UK and internationally, but additional novel themes emerged, underscoring the value of this collaborative approach.

CONCLUSION: Our survey revealed the value of including the voices of diverse individuals affected by Long Covid and those working in this area and highlighted priorities for social science in the field of Long Covid research.},
}

Humans
*COVID-19/therapy
*Social Sciences
Surveys and Questionnaires
Female
Male
*Research
SARS-CoV-2
Adult
Middle Aged
Health Personnel

@article {pmid41282857,
year = {2025},
author = {Dunckley, N and Zhang, N and Adler, CH and Shill, HA and Mehta, S and Driver-Dunckley, E and Belden, CM and Atri, A and Choudhury, P and Kuramoto, A and Serrano, GE and Beach, TG},
title = {Post-Acute COVID-19 Effects on Diagnostic Conversion Rates And Standardized Cognitive and Motor Test Scores in a Longitudinal Study of Independent, Community-Recruited Elderly Subjects.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.20.25338408},
pmid = {41282857},
abstract = {There is considerable concern about the long-term consequences of COVID-19 infection, generally referred to as post-acute sequelae, including declines in cognitive and motor abilities. The degree to which COVID-19 contributes additional burden to normal aging trajectories remains unclear. Additionally, the impact of COVID-19 on subjects under study for age-related neurological diseases is a potential confounder that needs definition. This study investigated whether having had a COVID-19 illness was associated with a differential decline in cognitive or motor function in older adults, utilizing data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP), a longitudinal clinicopathological study based in metropolitan Phoenix, Arizona. Subjects were included if they 1) had completed a questionnaire about their experience with COVID-19 illness 2) were classified as cognitively normal at pre-pandemic diagnostic cognitive consensus conferences and 3) had one or more subsequent diagnostic conferences between July 1, 2020 and August 30, 2025. All subjects had serial standardized research-dedicated clinical evaluations including the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale (UPDRS). Specific objectives were to compare, between those who reported having had or not having had COVID-19, rates of conversion to cognitive impairment or dementia as well as pre-pandemic and final MoCA and UPDRS motor scores. A total of 100 subjects self-reported having had COVID-19 while 71 denied having had it. Their related acute illness severity was generally mild, with only 10% having had hospital treatment and none having required ventilator support. Post-acute symptoms were also mild; only 1 subject reported having "long Covid". Both cognitive and motor performance, as measured by MoCA and UPDRS part 3 scores, declined slightly (not statistically significant) over the study period. Conversion of cognitive diagnosis from normal to impaired or dementia occurred in 26% of those having had COVID-19 and in 32% of those not having had COVID-19; the difference was not significant. All subjects diagnosed with PD at the start of the study were also diagnosed with PD at the end of the study; no subjects converted from not having to having probable PD. Logistic regression analysis indicated that subjects' report of having had COVID-19 was not significantly associated with conversion to cognitive impairment or dementia while greater age, male sex, possession of one or more apolipoprotein E-ε4 alleles, and a diagnosis of probable PD all conferred a significantly greater likelihood of conversion. The results suggest that having a mild COVID-19 illness is not associated with greater declines on cognitive or motor screening tests than would be expected from age-related changes alone. Limitations of this analysis include small sample sizes, potential misclassification of COVID-19 status, and reliance on relatively crude clinical metrics that may miss significant functional changes. Additionally, we were unable to separately assess for varying COVID-19 severity dependent on whether or not the subject had been vaccinated, the number and type of vaccinations, and the particular SARS-CoV-2 variants that were circulating at the time of illness.},
}

@article {pmid41282756,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Long COVID Longitudinal Symptoms Burden Clusters Within A National Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.25339283},
pmid = {41282756},
abstract = {BACKGROUND: Long COVID is clinically heterogeneous, with evolving symptom trajectories that complicate classification. Prior clustering studies often rely on Electronic Health Records data, risking underreporting. We used longitudinal, community-based data to characterize symptom clusters and risk factors.

METHODS: We analyzed CHASING COVID Cohort participants with confirmed SARS-CoV-2 infection between December 2020 and December 2022, ≥12 months of follow-up, and long COVID (≥1 new symptom and concurrent activity limitation 3-12 months post-infection, both absent pre-infection). The infection in this window was the index infection; those with pre-index long COVID were excluded. Symptoms were self-reported pre-infection and at ∼3, 6, 9, and 12 months. Missing data were handled via multiple imputation by chained equations (30 datasets). Longitudinal K-means clustering was performed within each imputed dataset, with hierarchical aggregation to derive final assignments. Multivariable logistic regression (adjusting for age, sex) assessed associations of demographic, clinical, and social factors with cluster membership. Within the highest-burden cluster, hierarchical clustering identified symptom phenotypes.

RESULTS: Of 1,787 infected participants, 511 met criteria (22% ≥50 years; 55% female; 60% White non-Hispanic; 54% mental health disorder; 7.2% immunodeficiency; 21% ≥2 comorbidities; 30% prior infection; 24% never vaccinated pre-index). Three clusters emerged: highest, moderate, and lowest burden. The highest-burden cluster (median 6 symptoms at 6 and 9 months) was characterized by fatigue (57%-74%), concentration difficulty, post-exertional malaise, myalgia, sleep disturbance, gastrointestinal symptoms, headache, irritability, and mobility limitations (each ∼46%-53%). The moderate cluster peaked at 3 symptoms (fatigue 42%); the lowest remained ∼1 symptom (fatigue 24% at 12 months). Older age (aOR 2.68, 95% CI 1.59-4.53), female sex (2.36, 1.48-3.76), mental health disorder (2.65, 1.65-4.25), and immunodeficiency (4.23, 1.71-10.51) were associated with highest vs lowest burden. Within the highest-burden cluster, three phenotypes emerged: neurological/multisystemic, psychiatric/neurological, and physical/respiratory.

CONCLUSIONS: Distinct long-COVID clusters and phenotypes underscore heterogeneity and support tailored management and risk stratification.},
}

@article {pmid41282714,
year = {2025},
author = {Pearson, ML and Laraway, BJ and Elias, ER and Bilousova, G and Haendel, MA and , },
title = {Understanding Comorbidities in Hypermobile Ehlers-Danlos Syndrome: Could a Viral Infection Lead to a Diagnosis?.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.22.25338573},
pmid = {41282714},
abstract = {UNLABELLED: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a complex, underdiagnosed connective tissue disorder characterized by widespread symptoms affecting multiple organ systems. Recent clinical observations suggest that individuals with hEDS may be at increased risk for persistent symptoms following COVID-19, commonly referred to as Long COVID. Using data from over 23 million patients across the United States, we examined associations between hEDS, COVID-19 infection, Long COVID, and related chronic conditions. We identified nearly 30,000 individuals with hEDS and found that the estimated prevalence was approximately 1 in 800, higher than previously recognized. While rates of COVID-19 infection were similar between patients with hEDS and matched controls, those with hEDS were significantly more likely to develop Long COVID. This risk was especially elevated among patients with hEDS with overlapping conditions commonly seen in post-viral syndromes, including autonomic dysfunction, immune dysregulation, and chronic fatigue. Specifically, individuals with postural orthostatic tachycardia, mast cell-related symptoms, or chronic fatigue syndrome had the highest rates of Long COVID. Cumulative incidence analysis revealed that many patients received an hEDS diagnosis only after a COVID-19 infection, suggesting that viral illness may exacerbate or reveal previously unrecognized symptoms. Patients with hEDS also exhibited higher odds of having additional risk factors for severe or prolonged illness, including chronic lung and autoimmune conditions, depression, and cerebrovascular disease. These findings highlight a previously unrecognized vulnerability in patients with hEDS and underscore the need for greater clinical awareness of their heightened risk for persistent post-COVID illness. Improved screening, earlier diagnosis, and integrated care pathways are urgently needed to support this complex and underserved patient population.

AUTHOR SUMMARY: We studied patients with hypermobile Ehlers-Danlos Syndrome (hEDS), a connective tissue condition that affects joints, skin, and many body systems. This condition is often misunderstood or overlooked, leaving many people undiagnosed. During the COVID-19 pandemic, people with hEDS appeared to experience more long-term symptoms after infection, a condition often called Long COVID. Here, we analyzed the health records of millions of patients in the United States to better understand post-viral outcomes.Patients with hEDS were more likely to be diagnosed with Long COVID compared to similar patients without hEDS. This was especially true for those who also had conditions such as chronic fatigue, immune conditions, or issues with heart rate and blood pressure regulation. In many cases, people were diagnosed with hEDS for the first time only after they had COVID-19, suggesting the virus may worsen or reveal symptoms that had been previously missed.Our findings show that hEDS may be more common than previously thought and that such patients face higher risks after COVID-19. Greater awareness and earlier recognition of hEDS could improve care for many patients with complex, long-lasting symptoms.},
}

@article {pmid41282703,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, M and Gebo, K and Nash, D},
title = {Effect of a Third COVID-19 Vaccine Dose on the Incidence of Long COVID Among Adults Who Completed a Primary Vaccine Series: a Target Trial Emulation in a Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.03.25339444},
pmid = {41282703},
abstract = {BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving >=1 third dose versus completing only a primary series on 6 and 12 month long COVID incidence using a target trial emulation in a U.S. community cohort.

METHODS: We analyzed the CHASING COVID Cohort, a prospective, community based study of U.S. adults. Eligible participants were >=18 years, had completed a two dose primary series, had no prior long COVID, and had no SARS-CoV-2 infection in the 3 months before time zero. Strategies compared were: receive a third dose at time zero vs. not receive a third dose during follow up. Long COVID was defined as >=1 new symptom at or beyond 3 months post infection with concurrent activity limitation, both absent in the prior year. Follow up was 6 and 12 months. We used a per protocol analog: participants were artificially censored upon deviating from their assigned strategy or lost to follow up, with inverse probability weights to address selection due to censoring and time varying confounding. We fit weighted pooled logistic models to estimate weighted incidence, differences, and ratios at each horizon.

RESULTS: Across 16 sequential trials (18,930 person trials; 4,044 unique individuals), 3,321 person trials received a third dose at time zero and 15,609 did not. At 6 months, weighted long COVID incidence was 0.9% (95% CI, 0.5%, 1.3%) with a third dose vs. 1.0% (0.8%, 1.1%) without (risk difference (RD), -0.1%; 95% CI, -0.5%, 0.4%; risk ratio (RR), 0.93; 95% CI, 0.54, 1.44). At 12 months, incidence was 4.9% (4.1%, 5.9%) with a third dose vs. 4.5% (4.1%, 4.8%) without (RD, 0.4%; 95% CI, -0.5%, 1.4%; RR, 1.09; 95% CI, 0.90, 1.33).

CONCLUSION: In this community based target trial emulation, receiving a third COVID-19 vaccine dose did not meaningfully reduce 6 or 12 month long COVID incidence compared with completing only a primary series.},
}

@article {pmid41282682,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, M and Gebo, K and Nash, D},
title = {Natural History of Self-reported Symptoms Following SARS-CoV-2 Infection: A Target Trial Emulation in a Prospective Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.25339316},
pmid = {41282682},
abstract = {BACKGROUND: The natural history of symptoms after SARS-CoV-2 infection remains uncertain because many studies are not representative, ignore background symptom prevalence, lack longitudinal tracking, and omit appropriate controls. Using a prospective, community-based cohort with repeated symptom measures, we estimated post infection risks of long COVID symptoms versus contemporaneous uninfected controls.

METHODS: We analyzed the CHASING COVID Cohort, a U.S. longitudinal study with surveys and serology (March 2020 to December 2023). Infection status (January 2021 to December 2022) was determined from self-reported PCR/antigen results, serology, or CSTE probable criteria. We emulated 24 monthly target trials comparing individuals newly infected at time zero with those remaining uninfected. Outcomes were new onset long COVID symptoms not reported pre-infection, assessed overall and within three clusters (neurological, autonomic, exercise intolerance) at 4 to 8 and 9 to 12 months post infection. Inverse probability of treatment and censoring weights adjusted for confounding and informative loss to follow up.

RESULTS: The analysis included 1,055 infected and 52,310 uninfected person-trials. At 4 to 8 months, the adjusted risk of any long-COVID symptom was 22.6% (95% CI 20.5, 24.8) among infected versus 11.3% (11.1, 11.5) among uninfected (adjusted risk difference [aRD], 11.3% [9.2, 13.5]; adjusted risk ratio [aRR], 2.01 [1.81, 2.20]). At 9 to 12 months, risks were 19.2% (17.0, 21.3) vs 12.4% (12.2, 12.7) (aRD, 6.7% [4.6, 8.9]; aRR, 1.54 [1.37, 1.72]). Across all three clusters, infected participants had consistently higher risks at both intervals.

CONCLUSIONS: SARS-CoV-2 infection was associated with elevated risk of new-onset long-COVID symptoms persisting up to 12 months. Using a national community based cohort, contemporaneous uninfected controls, and target trial emulation clarifies the burden attributable to infection and supports ongoing surveillance and targeted prevention and care.},
}

@article {pmid41282213,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and Alarab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: Lung Pathophysiology and its Relationship with Cognitive Dysfunction.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7464124/v1},
pmid = {41282213},
issn = {2693-5015},
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and 129 Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age=54±11 yrs.; 10 females) that were 32±5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower 129 Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}

@article {pmid41282195,
year = {2025},
author = {Dominguez, JC and Fowler, KC and Koralnik, IJ and Liow, K and Ampil, E and Zhi, Q and Laxamana, L and Berroya, R and Noris, CJ and Meropol, SB and Troxel, AB},
title = {Analysis of the National Institutes of Health COVID-19 Neuro Databank by geographic region and income status.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7371770/v1},
pmid = {41282195},
issn = {2693-5015},
abstract = {Background While COVID-19 is more commonly known to present and persist in terms of respiratory symptoms, evidence for neurologic manifestations is limited. Objectives This study aims to provide an epidemiological overview of neurologic manifestations of COVID-19. It compares the demographic and clinical profiles of patients based on geographic location and country income classification. Moreover, it describes the neurologic manifestations of Long COVID. Methods This was a cross-sectional analysis of a multi-country cohort of patients with COVID-19-associated neurologic symptoms enrolled in the COVID-19 Neuro Databank from January 2020 to February 2025. Demographic, clinical and health system-related factors were described. Comparisons among geographic regions and income classifications were performed via analysis of variance and chi-square tests or Fisher's exact tests. Results Majority of the 3,901 patients were from the United States (U.S.) and from high-income countries. The mean age was 57.27±18 years and 54% were males. Neurologic comorbidities were highest in the U.S. whereas non-neurologic comorbidities. Asia had the greatest frequency of severe COVID and mortality. Vaccination and use of COVID-19 medication was lowest in Africa. There were significant associations between COVID-19 vaccination and use of COVID-19 medications with income level. The five leading COVID-19-associated neurologic conditions were neurocognitive disorders, fatigue, headache, anosmia, and ageusia. A subset of Long COVID was identified as thought disorders, fatigue, mood disorders, stroke, headache, and neurocognitive disorders. Conclusions This study provides insight into the varying profile and burdens of COVID-19 associated neurologic conditions and the health inequities during the pandemic among geographic and income groups.},
}

@article {pmid41280901,
year = {2025},
author = {Fricke, F and Mai, F and Wossidlo, C and Steinbeck, F and Bergmann-Ewert, W and Kordt, M and Kraft, K and Müller, B and Reisinger, EC and Müller-Hilke, B},
title = {Transcriptome analysis of classical blood cells reveals downregulation of pro-inflammatory genes in the classical monocytes of long COVID patients.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1710783},
pmid = {41280901},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/genetics/blood ; *Monocytes/immunology/metabolism ; Male ; Female ; Gene Expression Profiling ; *SARS-CoV-2/immunology ; Middle Aged ; Down-Regulation ; Adult ; *Transcriptome ; Inflammation/genetics/immunology ; Single-Cell Analysis ; Cytokines/blood ; Aged ; Leukocytes, Mononuclear/immunology ; },
abstract = {INTRODUCTION: Despite extensive research, the pathogenesis and predispositions underlying long COVID (long-term coronavirus disease 2019) remain poorly understood.

METHODS: To address this, we analyzed the immunological landscapes of 44 patients with long COVID and 44 matched convalescents using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and validated the findings with plasma cytokine measurements via Luminex technology.

RESULTS: While the immune cell compositions showed minimal quantitative differences only among natural killer (NK) cells, the transcriptome analyses identified distinct gene expression patterns, particularly in classical monocytes: patients with long COVID exhibited downregulation of the inflammation-associated genes, including IL1B and CXCL2. Imputation of the transcription factor activity hinted at a reduced inflammasome activity (via SNAI1) and an impaired monocyte differentiation (via ATF2) in long COVID. The RNA velocity data supported the presence of immature classical monocytes in these patients.

DISCUSSION: These findings show that monocytes might be dysregulated and/or exhausted in patients with long COVID.},
}

Humans
*COVID-19/immunology/genetics/blood
*Monocytes/immunology/metabolism
Male
Female
Gene Expression Profiling
*SARS-CoV-2/immunology
Middle Aged
Down-Regulation
Adult
*Transcriptome
Inflammation/genetics/immunology
Single-Cell Analysis
Cytokines/blood
Aged
Leukocytes, Mononuclear/immunology

@article {pmid41280592,
year = {2025},
author = {},
title = {Erratum: An audit of 12 cases of long COVID following the Lightning Process intervention examining benefits and harms.},
journal = {Journal of family medicine and primary care},
volume = {14},
number = {10},
pages = {4407},
pmid = {41280592},
issn = {2249-4863},
abstract = {[This corrects the article on p. 796 in vol. 14, PMID: 40115575.].},
}

@article {pmid41279626,
year = {2025},
author = {Liu, JA and Chaulagain, S and Creisher, PS and Zhong, W and Zhang, T and Taddese, M and Shi, K and Park, HS and Hcnir, H and Arnold, AP and Baric, RS and Barahona, NB and Engler-Chiurazzi, EB and Zwezdaryk, KJ and Thio, CL and Balagopal, A and Harkema, JR and Thompson, EA and Pekosz, A and Cox, AL and Klein, SL},
title = {Mechanisms of sex differences in acute and long COVID sequelae in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.13.682101},
pmid = {41279626},
issn = {2692-8205},
abstract = {While males are more likely to suffer severe outcomes during acute COVID-19, a greater proportion of females develop post-acute sequalae of COVID-19 (PASC) despite similar rates of infection. To identify mechanisms of PASC, mice were infected with SARS-CoV-2 and viral, inflammatory, and behavioral outcomes were evaluated through 84 days post infection. Sex differences were not observed in virus replication or persistence of viral RNA in pulmonary or extrapulmonary tissues in acute or PASC phases. Following recovery from infection, female mice exhibited persistent neurocognitive and behavioral impairments, along with greater frequencies of inflammatory myeloid subsets, neuroinflammation, and dysregulated T cell subsets, including Tregs. Sex differences in inflammation and cognitive phenotypes during PASC were mediated by the presence of two X chromosomes. XX animals independent of chromosome Y presented with neuroinflammation and PASC along with infection-induced upregulation of the X-linked genes Xist and Tlr7 that regulate inflammation and chronic disease outcomes.},
}

@article {pmid41278460,
year = {2025},
author = {Zheng, T and Gao, R and Liu, Y and Wang, Y and Wu, C and Guo, L and Chen, L and Wang, X and Xiao, Y and Zhong, J and Zhang, R and Wang, Y and Ren, X and Cao, B and Ren, L and Wang, J},
title = {T cell-driven sustained inflammation and immune dysregulation mimicking immunosenescence for up to three years post-COVID-19.},
journal = {Immunity & inflammation},
volume = {1},
number = {1},
pages = {11},
pmid = {41278460},
issn = {3059-4774},
abstract = {UNLABELLED: Long COVID has emerged as a major global health concern, yet the long-term trajectory of immune recovery and its contribution to persistent symptoms remain to be elucidated. Here, we conducted a three-year longitudinal follow-up of the 47 COVID-19 patients and applied single-cell RNA sequencing (scRNA-seq) and multiplex cytokine profiling to comprehensively characterize the peripheral immune landscape during convalescence. We observed persistent immune dysregulation up to three years post-infection, characterized by chronic inflammation and impaired restoration of naïve CD4[+] T cells, naïve CD8[+] T cells, and SLC4A10[+] MAIT cells-features reminiscent of immunosenescence. Notably, Th17 cells, rather than monocytes, emerged as key drivers of chronic inflammation beyond one year. We identified two distinct Th17 subsets: RORC[+] Th17 cells and LTB[+] Th17 cells. While RORC[+] Th17 cells were negatively correlated with inflammatory cytokine levels, LTB[+] Th17 cells showed proinflammatory features and were positively associated with long COVID symptoms. Sustained elevation of S100A8 and IL-16 in follow-up patients may contribute to the persistent presence of LTB[+] Th17 cells. Together, our study provides an in-depth longitudinal map of immune remodeling in COVID-19 convalescents, revealing key cellular and molecular drivers of sustained inflammation up to three years post-infection.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44466-025-00012-2.},
}

@article {pmid41277895,
year = {2025},
author = {Cabello Fernandez, C and Didone, V and Lesoinne, A and Slama, H and Fery, P and Rousseau, AF and Moutschen, M and , and Collette, F and Willems, S},
title = {Cognitive and affective psychoeducation for Long COVID: a randomized controlled trial.},
journal = {Brain communications},
volume = {7},
number = {6},
pages = {fcaf447},
pmid = {41277895},
issn = {2632-1297},
abstract = {Long COVID is a complex condition characterized by persistent symptoms, including cognitive difficulties and fatigue, which significantly impact daily functioning. Although various intervention strategies inspired by approaches used in the rehabilitation of other neurological conditions have been developed to address these issues, evidence of their efficacy in Long COVID populations remains limited. This study aimed to compare the effectiveness for cognitive complaints of two psychoeducational interventions-one focused on cognitive difficulties and the other on affective symptoms in Long COVID patients with cognitive problems. COVCOG (Long COVID: treatment of cognitive difficulties) is a randomized controlled trial using a parallel two-group design. Long COVID patients underwent neuropsychological assessments at pre-, 2- and 8-month post-intervention. The intervention comprised four 90-min sessions of either a cognitive-focused or an affective-focused psychoeducational programme. The effects were measured on cognitive complaints (primary outcome), cognitive performance, fatigue, sleep difficulties, quality of life, psychological distress, and impact on work and daily activities (secondary outcomes). Linear mixed models (LMMs) were used. One hundred and thirty Long COVID patients were randomized. One hundred and twenty-two (mean age: 47 ± 10; 69.7% female) were included (63 in the cognitive group and 59 in the affective group). The low dropout rate (12% at 2 months and 9% at 8 months post-intervention) and the patients' substantial active engagement-92% attended all intervention sessions-assured the feasibility of both interventions. LMM analysis revealed a statistically significant improvement with time in subjective cognitive complaints, objective cognitive performance (attention, working memory and long-term memory), quality of life, fatigue, sleep, some psychological distress subscales and work impairment (all Ps < 0.03, with small to moderate effect sizes), but no group-by-time interaction, suggesting that trajectories did not differ between arms. However, some improvements are specific to one intervention or the other. Designed specifically for this population, both psychoeducative interventions provide insights into improving the management of Long COVID patients with cognitive problems. Longer treatment may be needed for more meaningful improvements. Clinicaltrials.gov: NCT05167266.},
}

@article {pmid41277355,
year = {2025},
author = {Foscolou, A and Pratti, T and Detopoulou, P and Argyri, K and Nikolaou, G and Kouskouti, A and Malikourti, A and Petrogianni, M and Shurdha, E and Psaroudaki, E and Panoutsopoulos, GI and Vamvakas, S and Gioxari, A},
title = {Dietary n-3 Polyunsaturated Fatty Acids From Fish Are Associated With Better Healthy Aging Indicators: Results of the DIAPELH Study.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {38},
number = {6},
pages = {e70169},
doi = {10.1111/jhn.70169},
pmid = {41277355},
issn = {1365-277X},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Fatty Acids, Omega-3/administration & dosage ; Aged ; Male ; Female ; Cross-Sectional Studies ; *Healthy Aging/physiology ; Greece/epidemiology ; Middle Aged ; *Fishes ; Animals ; Diet, Mediterranean/statistics & numerical data ; *Seafood ; COVID-19/epidemiology ; *Diet ; Cognition ; Aged, 80 and over ; Depression/prevention & control ; SARS-CoV-2 ; Aging ; },
abstract = {INTRODUCTION: Promoting healthy aging is a public health goal, especially in regions with a high proportion of older adults, such as Greece. This cross-sectional study investigated the association of fish n-3 PUFA intake with indicators of healthy aging among older Greek Peloponnesian adults.

METHODS: In total, 449 individuals > 60 years of age were enroled. Sociodemographic, anthropometrical, medical, mobility, balance, lifestyle, dietary, cognitive and mental characteristics were assessed through validated questionnaires and procedures.

RESULTS: Analyses revealed that n-3 PUFA intake was associated with fewer depression symptoms (p < 0.001), higher cognition levels (p = 0.012) and levels of healthy aging (p < 0.001), derived from Successful Aging Index (SAI). In parallel, n-3 PUFA intake was associated with higher adherence to the Mediterranean diet (p < 0.001). Additionally, n-3 PUFA intake was inversely correlated with the presence of long COVID-19 symptomatology (p = 0.036). No association of n-3 PUFA intake with mobility or physical performance and balance (all ps> 0.05) was detected.

CONCLUSION: The results underscore the significance of nutrition in older adults, highlighting the possible protective impact of n-3 PUFAs on maintaining functionality. Future prospective studies may validate these associations and contribute to the development of targeted nutritional strategies for older adults.},
}

Humans
*Fatty Acids, Omega-3/administration & dosage
Aged
Male
Female
Cross-Sectional Studies
*Healthy Aging/physiology
Greece/epidemiology
Middle Aged
*Fishes
Animals
Diet, Mediterranean/statistics & numerical data
*Seafood
COVID-19/epidemiology
*Diet
Cognition
Aged, 80 and over
Depression/prevention & control
SARS-CoV-2
Aging

@article {pmid41277094,
year = {2025},
author = {Mustonen, T and Kytölä, P and Lantto, H and Lager, E and Vangelova-Korpinen, V and Virrantaus, H and Sulg, A and Stålnacke, S and Posharina, T and Luukkonen, R and Uusitalo, A and Piirilä, P and Kanerva, M},
title = {Characterization of sympathicotonia in post-covid condition (long covid) and healthy controls using long-term electrodermal activity (EDA) follow-up.},
journal = {Clinical physiology and functional imaging},
volume = {45},
number = {6},
pages = {e70037},
doi = {10.1111/cpf.70037},
pmid = {41277094},
issn = {1475-097X},
support = {101057553//European Union's Horizon Europe research and innovation/ ; Y780022061//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; Y780024073//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; Y780023041//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/complications/physiopathology/diagnosis ; Middle Aged ; *Galvanic Skin Response ; Adult ; *Sympathetic Nervous System/physiopathology ; Case-Control Studies ; Time Factors ; Aged ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; },
abstract = {PURPOSE: After SARS-CoV-2 infection, some patients develop post-COVID condition (PCC), often associated with sympathicotonia. This study aimed to characterize sympathicotonia in PCC patients using a novel long-term electrodermal activity (EDA) analysis via a smart ring and evaluate its clinical applicability.

METHODS: Seventeen PCC patients were recruited from a Long Covid outpatient clinic, and 18 healthy controls volunteered. PCC patients were divided based on self-reported symptoms into those with or without sympathicotonia. A 14-day EDA monitoring was conducted. Sympathetic nervous system (SNS) activity was expressed as a double normalized index of electrodermal activity (DNE), with higher levels indicating higher SNS activity. Orthostatic tests were performed to identify orthostatic sympathicotonia. DNE levels, representing EDA, were compared to self-reported and orthostatic sympathicotonia.

RESULTS: DNE levels did not differ between PCC patients with (N = 12) or without (N = 5) self-reported sympathicotonia or compared with nonsympathetic controls. When dividing all participants by orthostatic test results, DNE levels were lower during day (08:00-14:00; p < 0.05) but higher during late night (00:00-02:00; p < 0.05) in those with orthostatic sympathicotonia (N = 21) compared to those without (N = 14), with the 24-h comparison significant (p = 0.022). Among PCC patients, DNE levels were higher in orthostatic nonsympathicotonic (N = 7) than orthostatic sympathicotonic (N = 10) during morning (09:00-12:00; p < 0.05), with the 24-h comparison significant (p = 0.044).

CONCLUSION: Self-reported symptoms did not distinguish sympathicotonia. However, individuals with orthostatic test-identified sympathicotonia had heightened EDA, indicating increased sympathetic activity, particularly during late night. PCC was not identifiable by EDA. Long-term EDA monitoring may provide an objective tool for detecting sympathicotonia independently of self-reported symptoms.},
}

Humans
Male
Female
*COVID-19/complications/physiopathology/diagnosis
Middle Aged
*Galvanic Skin Response
Adult
*Sympathetic Nervous System/physiopathology
Case-Control Studies
Time Factors
Aged
Post-Acute COVID-19 Syndrome
Follow-Up Studies

@article {pmid41274384,
year = {2025},
author = {Schmitz, B and Garbsch, R and Schäfer, H and Bär, C and Chatterjee, S and Riemekasten, G and Schulze-Forster, K and Heidecke, H and Schultheiß, C and Binder, M and Mooren, FC},
title = {Autonomic dysfunction and vasoregulation in Long COVID-19 are linked to anti-GPCR autoantibodies.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2025.10.034},
pmid = {41274384},
issn = {1097-6825},
abstract = {BACKGROUND: SARS-CoV-2-triggered autoantibodies (AAB) targeting G protein-coupled receptors (GPCRs) have been suggested to contribute to the post-acute sequelae of COVID-19 (Post-COVID-19 Syndrome, PCS).

OBJECTIVE: To characterize AABs involved in autonomic dysfunction such as rhythm control and vasoregulation in patients with post-acute sequelae of COVID-19 and profile the peripheral B- and T-cell receptor (B/TCR) architecture to identify immunogenetic imprints of autoimmunity.

METHODS: Anti-GPCR AABs were characterized in patients with post-acute sequelae of COVID-19 with known alteration in autonomic nervous system functions assessed by heart rate variability (HRV). Adaptive immune receptor repertoire sequencing (AIRR-seq) was used to profile peripheral BCR and TCR architecture. COVID-19 patients with severe or moderate acute disease, after recovery, and pre-pandemic healthy individuals served as controls. Cardio- and vasoactive effects of AABs were analyzed using 24h and exercise test blood pressure measurements. The direct effect of AABs on electromechanical coupling was tested in human induced pluripotent stem cell cardiomyocytes.

RESULTS: AABs including AGT1/2Rab, ADRB1/2ab, M1/3Rab, and CXCR3ab were associated with HRV alterations. Analysis of the broad BCR repertoire metrics revealed high similarity between PCS patients and healthy controls for clonality and diversity measures. The level of somatic hypermutation as proxy for antigen-experience was equal to healthy controls. Elevated CXCR3ab levels were linked to higher 24h mean arterial pressure, while patients with elevated M1Rab and CXCR3ab levels showed higher blood pressure during stress tests. AABs had no effect on beat frequence and amplitude of cardiomyocyte contraction in vitro.

CONCLUSIONS: These findings suggest that AABs play a modulatory role in sympathetic nervous system-mediated regulation of cardiac rhythm and vascular function in PCS. AAB levels did not correlate with B- and T-cell receptor repertoire metrics or TRBV gene usage.},
}

@article {pmid41273342,
year = {2025},
author = {Zuccarelli, L and Baldassarre, G and Bondesan, A and Caroli, D and De Micheli, R and Tringali, G and Favaretto, T and Suraj-Prazmowska, J and Kurpinska, A and Majerczak, J and Chlopicki, S and Zoladz, JA and Sartorio, A and Grassi, B},
title = {Impaired nitric oxide-dependent endothelial function in young male individuals with obesity before the onset of symptoms and complications.},
journal = {Experimental physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/EP093109},
pmid = {41273342},
issn = {1469-445X},
support = {//Italian Ministry of Health - ricerca corrente/ ; 2020EM9A8X//Ministero dell'Istruzione dell'Università e della Ricerca/ ; 2022LBBKHX//Ministero dell'Istruzione dell'Università e della Ricerca/ ; G53D23005610006//Ministero dell'Istruzione dell'Università e della Ricerca/ ; P2022XX7YL//Ministero dell'Istruzione dell'Università e della Ricerca/ ; G53D2300747000//Ministero dell'Istruzione dell'Università e della Ricerca/ ; //'Long-COVID syndrome: pathophysiology of the impaired exercise tolerance'/ ; //'Central (cardiorespiratory) and peripheral (muscular) determinants of functional deterioration in COPD: new biomarkers for evaluating disease severity and acute exacerbations?'/ ; N43/DBS/000221//Jagiellonian University Collegium Medicum/ ; N43/DBS/000315//Jagiellonian University Collegium Medicum/ ; 06/IDUB/2019/94//qLIFE Priority Research Area under the Excellence Initiative - Research University Programme at the Jagiellonian University/ ; },
abstract = {Endothelial dysfunction drives obesity-related complications. Doppler ultrasound measurement of blood flow during 1-min passive leg movements (PLM) is a valuable non-invasive tool for assessing endothelial function and nitric oxide (NO)-mediated vasodilation. The objectives of this work were t o identify endothelial dysfunction biomarkers in young individuals with obesity (OB) using the PLM test; to evaluate the effects of a rehabilitation programme on these biomarkers; and to explore associations between PLM data, oxidative metabolism and blood biomarkers of microvascular impairment. Fifteen male OB (age 17 ± 4 years; body mass 121.4 ± 24.1 kg; body mass index 39.3 ± 7.5 kg m[-2]) were tested before (PRE) and after (POST) a 3-week multidisciplinary body mass reduction programme. Fifteen age-matched normal-weight males (CTRL) underwent PRE measurements. Participants performed an incremental exercise, a PLM test and underwent blood biomarker analysis. Peak oxygen uptake and ventilatory thresholds (mL kg[-1] min[-1]) were ∼40% lower in OB versus CTRL (P < 0.001) and improved by ∼8% in OB POST versus PRE (P < 0.05). Plasma nitrite concentration was lower in OB (0.18 ± 0.09 µmol L[-1]) versus CTRL (0.51 ± 0.49; P = 0.02). Baseline blood flow, normalized for appendicular muscle mass, was similar between the two groups, whereas peak blood flow, Δpeak (difference between peak and baseline) and the area under the blood flow versus time curve were significantly lower in OB PRE, with improvements in OB POST. Several blood biomarkers of endothelial barrier function and permeability differed in OB versus CTRL. The blunted PLM-induced hyperaemic response and lower plasma nitrite levels indicate impaired endothelial function in young individuals with obesity, occurring before the onset of cardiovascular and metabolic complications.},
}

@article {pmid41272382,
year = {2025},
author = {Dornas, W and Reis, JP and Belilo, TE and Vaz, LG and Nasser, HH and de Souza Maia, ML and Figueiredo, A and Tcherniacovski, AG and Montenegro, LCC and Yang, X and C Santiago, H},
title = {Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41272382},
issn = {1568-5608},
abstract = {Post-acute sequelae of Covid-19 (PASC) refer to persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. However, identifying biological mechanisms, potential therapeutic targets, and modifiable environmental risk factors remains necessary. Here, we analyzed cytokine levels in patients with PASC through a systematic literature search of the PubMed/MEDLINE, Web of Science, and Scopus databases, including articles published up to December 2024. A total of 33 studies (comprising 3294 patients) were included, addressing the long-term sequelae following acute Covid-19 infection. Levels of IL-6, IL-2, MCP-1/CCL2, TNF-α, IFN-γ, and IP-10/CXCL10 were higher in Covid-19 patients with PASC compared to those without PASC, suggesting an inflammatory basis for the persistence of symptoms. Conversely, little or no difference was observed for IL-1β, IL-7, IL-10, IL-4, IL-17A, IL-8, and IL-1α. To assess the duration of the sustained inflammatory response post-infection, cytokine measurements were categorized as < 6 months or ≥ 6 months after diagnosis. IL-6, MCP-1/CCL2, TNF-α, and IFN-γ remained elevated in both time windows, while IL-1β, IL-8, IP-10/CXCL10, IL-2, and IL-10 showed increased levels beyond 6 months post-Covid-19 diagnosis. Our findings indicate that persistent elevation of inflammatory cytokine is associated with PASC, contributing to a better understanding of the immune pathology underlying chronic dysfunction related to Covid-19.},
}

@article {pmid41271803,
year = {2025},
author = {Bansal, A},
title = {Economic burden of long COVID: macroeconomic, cost-of-illness and microeconomic impacts.},
journal = {NPJ primary care respiratory medicine},
volume = {35},
number = {1},
pages = {53},
pmid = {41271803},
issn = {2055-1010},
mesh = {Humans ; *COVID-19/economics/epidemiology ; *Cost of Illness ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health ; Unemployment ; },
abstract = {Long COVID, defined by symptoms persisting three months post-SARS-CoV-2 infection, presents a significant global health and economic challenge, with global prevalence estimated at 36% (ranging from 1-92%). This brief communication consolidates current knowledge on its economic impacts, including macroeconomic, cost-of-illness, and microeconomic impacts, which are estimated at an average annual burden of $1 trillion globally and $9000 per patient in the USA, with some individuals covering substantial out-of-pocket expenses. Annual lost earnings in the USA alone are estimated at approximately $170 billion. Long COVID was associated with increased unemployment, financial distress, and work impairment for up to three years post-infection. This paper highlights discrepancies in impact estimation methodologies and calls for standardised metrics especially in emerging economies. Key research gaps include the absence of comprehensive longitudinal studies on individual and aggregated economic burden, specific long COVID phenotypes and biomarkers, and cost-effectiveness evaluations of interventions.},
}

Humans
*COVID-19/economics/epidemiology
*Cost of Illness
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Global Health
Unemployment

@article {pmid41271424,
year = {2025},
author = {Seboka, BT and Smith, J and Whitmore, K and Baranow, B and Howden, E and Kulkarni, J and Huynh, QL and H Marwick, T},
title = {Depression as a moderator and mediator of functional status in patients with Long COVID: a cross-sectional and longitudinal observational study from the PERCEIVE cohort in Australia.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e099776},
doi = {10.1136/bmjopen-2025-099776},
pmid = {41271424},
issn = {2044-6055},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *COVID-19/psychology/complications/epidemiology/physiopathology ; Longitudinal Studies ; Middle Aged ; *Depression/epidemiology ; Adult ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; Tasmania/epidemiology ; Victoria/epidemiology ; },
abstract = {BACKGROUND: In patients with post-acute sequelae of COVID-19 (PASC), depression has been associated with symptom severity, the duration since infection and ongoing functional impairment. However, the interconnections between these factors remain inadequately understood.

OBJECTIVES: This study aimed to explore the roles of depressive symptoms in moderating and mediating the relationships between post-COVID-19 conditions and functional capacity.

METHODS: The PERCEIVE study recruited 1794 participants from Victoria and Tasmania through online advertisements based on possible PASC for a cross-sectional study. Of these, 461 participated in the longitudinal study. Post-COVID-19 duration and symptoms were recorded, and depressive symptoms and functional capacity were self-reported using the 9-item Patient Health Questionnaire and the Duke Activity Status Index (DASI), respectively. The association of depression with functional capacity was explored using ordinary least squares (OLS) regression, with companion OLS models, Sobel-Goodman tests and 1000 bootstrap iterations to assess mediation. Longitudinal data were analysed to assess changes in functional capacity and depressive symptoms over time, with mediation analysis using mixed models to explore depression as a mediator.

RESULTS: Participants had a mean DASI score of 35 (SD 21). Fatigue (18%), shortness of breath (11%) and chest pain (6%) were common symptoms, with severe depression linked to fatigue (93%) and shortness of breath (66%). The severity of post-COVID-19 symptoms was associated with severe depression (β=6.31, 95% CI 5.42 to 7.21) and reduced functional capacity (β=-6.40, 95% CI -9.20 to -3.61), with depression mediating 36% of the association between post-COVID-19 symptom severity and functional capacity. PASC was associated with higher depression scores (β=2.06, 95% CI 1.15 to 2.97) and lower functional capacity (β=-3.99, 95% CI -6.21 to -1.77), with depression mediating 51% of the association between PASC and reduced functional capacity. The longitudinal analysis suggested that depression is associated with the relationship between PASC and changes in functional capacity over time (unstandardised estimate=-5.16, p<0.001).

CONCLUSION: Depression plays a key role in exacerbating post-COVID-19 functional impairment. This observation underscores the need for targeted physical and mental health interventions to enhance long-term recovery for those with severe conditions.},
}

Humans
Male
Female
Cross-Sectional Studies
*COVID-19/psychology/complications/epidemiology/physiopathology
Longitudinal Studies
Middle Aged
*Depression/epidemiology
Adult
SARS-CoV-2
Aged
Severity of Illness Index
Post-Acute COVID-19 Syndrome
Tasmania/epidemiology
Victoria/epidemiology

@article {pmid41269680,
year = {2025},
author = {Pant, S},
title = {Resistance Training Improves Long COVID Outcomes.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2025.19746},
pmid = {41269680},
issn = {1538-3598},
}

@article {pmid41269415,
year = {2025},
author = {de Almeida Gomes, I and Braga-Neto, P and Matos, TL and da Silva, EL and de Oliveira, LLB and Lima, LB and Tavares-Júnior, JWL and Moura, AEF and de Andrade, MH and de Maria Frota Vasconcelos, T and Oriá, RB and Oliveira, DN and Sobreira-Neto, MA and Souza, PFN and de Moraes, MEA and Mesquita, FP and Montenegro, RC},
title = {Associations Between APOE Polymorphisms, Neurological Symptoms, and Cognitive Assessments in Long COVID Patients: An Analysis of SNPs rs7412 and rs429358.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {113},
pmid = {41269415},
issn = {1559-1182},
mesh = {Humans ; *Polymorphism, Single Nucleotide/genetics ; Male ; Female ; *COVID-19/genetics/complications/psychology ; *Apolipoproteins E/genetics ; Middle Aged ; *Cognition/physiology ; Aged ; Genetic Predisposition to Disease ; Genetic Association Studies ; Alleles ; Genotype ; Adult ; },
abstract = {Long COVID has been associated with persistent neurological symptoms that impair cognitive function and quality of life, raising questions about the role of genetic factors in symptom severity and persistence. Apolipoprotein E (APOE) polymorphisms, known for their relevance in neurodegenerative diseases, may significantly influence neurological outcomes in long COVID patients. This study aimed to investigate the relationship between APOE polymorphisms, specifically single nucleotide polymorphisms (SNPs) rs7412 and rs429358, and neurological and cognitive symptoms in long-term COVID patients. APOE genotypes were identified through the analysis of SNPs rs7412 and rs429358. Cognitive and behavioral assessments were conducted using the Mini-Mental State Examination (MMSE), the Pfeffer Functional Activities Questionnaire, the Beck Inventory for mood assessment and the Epworth Sleepiness Scale (ESS). Statistical analyses included Mann-Whitney U test, chi-square or Fisher's exact test, and odds ratio calculation, using R Studio and GraphPad Prism. The results indicated that the ε2ε3 genotype was associated with lower scores on the BECK, suggesting fewer depressive symptoms, while the ε3ε3 genotype was linked to an increase in depressive symptoms. Furthermore, analyses of APOE alleles showed an opposite pattern concerning daytime sleepiness: carriers of the ε2 allele exhibited greater daytime sleepiness, whereas ε3 allele carriers reported less sleepiness, as measured by the ESS. The analysis of the rs7412 SNP revealed significant impacts on both BECK and ESS scores. These findings suggest that APOE polymorphisms, particularly the ε2 and ε3 alleles, play a crucial role in modulating neurological and cognitive symptoms associated with long COVID. The results highlight the potential of genetic screening to identify patients at higher risk of persistent cognitive and emotional alterations, emphasizing the importance of personalized management strategies and the need for further research in diverse populations.},
}

Humans
*Polymorphism, Single Nucleotide/genetics
Male
Female
*COVID-19/genetics/complications/psychology
*Apolipoproteins E/genetics
Middle Aged
*Cognition/physiology
Aged
Genetic Predisposition to Disease
Genetic Association Studies
Alleles
Genotype
Adult

@article {pmid41268552,
year = {2025},
author = {Rosa, BA and Bigham, M and Darling, TL and Arun, A and Singh, KS and Martin, J and Boon, ACM and Mitreva, M},
title = {Hookworm infection modulates lung and intestinal transcriptomic responses to SARS-CoV-2 in Syrian hamsters.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1701728},
pmid = {41268552},
issn = {1664-3224},
mesh = {Animals ; *COVID-19/immunology/genetics/virology ; *SARS-CoV-2/immunology/physiology ; *Transcriptome ; *Lung/immunology/virology/metabolism ; Mesocricetus ; *Intestines/immunology/virology ; Cricetinae ; Disease Models, Animal ; Coinfection/immunology ; *Ancylostoma/immunology ; *Hookworm Infections/immunology ; Humans ; Gene Expression Profiling ; Male ; },
abstract = {BACKGROUND: Helminth infections are widespread in resource-limited settings, and modulate host immune responses, with potential implications for viral coinfections. Intestinal helminths can alter susceptibility to respiratory viruses, but the mechanisms influencing SARS-CoV-2 infection outcomes remain poorly understood.

METHODS: Using the Syrian hamster model, we investigated the impact of prior infection with the human hookworm Ancylostoma ceylanicum on host responses to SARS-CoV-2. Tissue-specific transcriptional responses were compared among four groups: naive, hookworm-only, SARS-CoV-2-only, and coinfected with both pathogens, 3 and 6 days post-viral infection. Viral titers and weight loss were assessed, and RNA-seq transcriptome profiles from lung and intestinal tissues were interrogated to identify differentially expressed genes and cellular pathways.

RESULTS: Prior hookworm infection did not significantly alter viral titers or weight loss compared to SARS-CoV-2 infection alone, but distinct transcriptional signatures compared were identified compared to either single infection. Coinfection uniquely differentially regulated hematopoiesis and B cell-associated genes (e.g., ATF5, IGHM, JCHAIN) in the lungs, and immune and stress response pathways and inflammation-associated genes (e.g. FOLR2, PLA2GF, FABP3) in the intestine. Genes and pathways differentially regulated by SARS-CoV-2 alone, but with attenuated transcriptional responses in the lungs of coinfected hamsters were observed, including the loss of upregulation of toll-like receptor signaling and previously proposed host biomarkers for COVID-19 severity (CHI3L1, HMOX1), Long COVID (FCG4/FCGR3A and FST) and mortality (FST). In the intestine, hookworm-associated suppression of type I interferon-related genes (TAP1, IRF7) was reversed with SARS-CoV-2 coinfection, highlighting pathogen-specific modulation of innate antiviral signaling. Genes and pathways consistently differentially regulated by with SARS-CoV-2 were consistent with expectations, and many hemoglobin pathways were differentially regulated with hookworm in the intestine. CIBERSORT analysis was estimated relative leukocyte abundances in each sample cohort.

CONCLUSION: Our findings demonstrate that A. ceylanicum infection reshapes host transcriptional responses to SARS-CoV-2 in a tissue-specific manner, enhancing B cell immunity in the lung while driving intestinal inflammation. Hookworm-induced immune modulation attenuated key SARS-CoV-2-responsive genes and pathways, suggesting potential mechanisms for reduced disease severity observed in helminth-endemic regions. These findings establish a molecular framework to better understand helminth, SARS-CoV-2 and host immune interactions, with relevance for other respiratory viral infections.},
}

Animals
*COVID-19/immunology/genetics/virology
*SARS-CoV-2/immunology/physiology
*Transcriptome
*Lung/immunology/virology/metabolism
Mesocricetus
*Intestines/immunology/virology
Cricetinae
Disease Models, Animal
Coinfection/immunology
*Ancylostoma/immunology
*Hookworm Infections/immunology
Humans
Gene Expression Profiling
Male

@article {pmid41268373,
year = {2025},
author = {Calleja-Conde, J and Echeverry-Alzate, V and Sánchez-Diez, S and Giné, E and Bühler, KM},
title = {Severe alcohol use and COVID-19: implications for physical and mental health.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1640207},
pmid = {41268373},
issn = {1664-0640},
abstract = {The COVID-19 pandemic has revealed and intensified the vulnerability of individuals with pre-existing medical and behavioral conditions, notably those related to substance use. Among these, chronic alcohol consumption represents a clinically significant, yet often under-addressed, vulnerability factor that may exacerbate both the acute severity and long-term consequences of SARS-CoV-2 infection. This narrative review examines the biological and clinical intersections between alcohol use and COVID-19, focusing on shared mechanisms of immune dysfunction, neuroinflammation, and disruption of the gut-brain axis. We synthesize current findings showing that both conditions compromise innate and adaptive immune responses, alter cytokine signaling, and weaken mucosal and blood-brain barriers. These changes contribute to cognitive and emotional dysregulation and may increase the risk of persistent neuropsychiatric symptoms, including those observed in Long COVID. In addition, we discuss how chronic alcohol use may alter host susceptibility to infection and affect the immune response to vaccination, with implications for treatment outcomes and recovery. Our findings highlight the need to integrate alcohol use disorder into COVID-19 risk assessments, clinical management, and long-term mental health care planning. A multidisciplinary approach is essential to address the overlapping biological pathways that link alcohol-related vulnerability to COVID-19 outcomes.},
}

@article {pmid41267377,
year = {2025},
author = {},
title = {Correction to "The effect of uninterrupted and interrupted sitting on vascular function in adults with long COVID".},
journal = {Physiological reports},
volume = {13},
number = {22},
pages = {e70658},
doi = {10.14814/phy2.70658},
pmid = {41267377},
issn = {2051-817X},
}

@article {pmid41266487,
year = {2025},
author = {Richards-Belle, A and Shafran, R and Rojas, NK and Stephenson, T and Carr, E and Chalder, T and Dalrymple, E and McOwat, K and Simmons, R and Pinto Pereira, SM and , },
title = {Fatigue in children and young people up to 24 months after infection with SARS-CoV-2.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {41105},
pmid = {41266487},
issn = {2045-2322},
support = {COV-LT-0022//National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI)/ ; MR/Y009398/1//UK Medical Research Council/ ; },
mesh = {Humans ; Child ; *COVID-19/complications/virology/epidemiology ; Female ; Male ; *Fatigue/etiology/epidemiology/diagnosis ; Adolescent ; Longitudinal Studies ; SARS-CoV-2/isolation & purification ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; },
abstract = {Persistent fatigue is common following acute SARS-CoV-2 infection. Little is known about post-infection fatigue trajectories in children and young people (CYP). This paper reports on a longitudinal analysis of the Children and Young People with Long COVID study. SARS-CoV-2-positive participants, aged 11-to-17-years at enrolment, responding to follow-ups at 3-, 6-, 12-, and 24-months post-infection were included. Fatigue was assessed via the Chalder Fatigue Scale (CFQ; score range: 0-11, with ≥4 indicating clinical case-ness) and by a single-item (no, mild, severe fatigue). Fatigue was described cross-sectionally and examined longitudinally using linear mixed-effects models. Among 943 SARS-CoV-2-positive participants, 581 (61.6%) met CFQ case-ness at least once during follow-up. A higher proportion of ever-cases (vs. never-cases) were female (77.1% vs. 54.4%), older (mean age 15.0 vs. 13.9 years), and met Post-COVID Condition criteria 3-months post-infection (35.6% vs. 7.2%). The proportion of CFQ cases increased from 35.0% at 3-months to 40.2% at 24-months post-infection; 15.9% meet case-ness at all follow-ups. Single-item mild/severe responses showed sensitivity (≥0.728) and specificity (≥0.755) for CFQ case ascertainment. On average, CFQ scores increased by 0.448 points (95% CI, 0.252 to 0.645) over 24-months, but there were subgroup differences (e.g., fatigue increased faster in females than males and improved slightly in those meeting Post-COVID Condition criteria 3-months post-infection while worsening in those not meeting criteria). Persistent fatigue was prominent in CYP up to 24 months after infection. Subgroup differences in scores and trajectories highlight the need for targeted interventions. Single-item assessment is a practical tool for screening significant severe fatigue.},
}

Humans
Child
*COVID-19/complications/virology/epidemiology
Female
Male
*Fatigue/etiology/epidemiology/diagnosis
Adolescent
Longitudinal Studies
SARS-CoV-2/isolation & purification
Cross-Sectional Studies
Post-Acute COVID-19 Syndrome

@article {pmid41265281,
year = {2025},
author = {da Silva, EM and de Campos, CM and de Godoy, CG and de Oliveira, DB and Alonso, AC and da Silva, VC and Schmitt, ACB and Ochiai, GS and Viana, BOC and da Silva, JM and de Carvalho, CRF and de Carvalho, CRR and D'Andréa Greve, JM and Pompeu, JE},
title = {Predictors of persistent fatigue one year after severe COVID-19: A prospective cohort study on depression and lung function.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100846},
doi = {10.1016/j.clinsp.2025.100846},
pmid = {41265281},
issn = {1980-5322},
abstract = {BACKGROUND: Fatigue is among the most enduring symptoms of long COVID. However, the relationship between persistent fatigue and factors such as physical performance, lung function, anxiety, and depression in severe cases of COVID-19 remains underexplored.

OBJECTIVES: To assess the prevalence of fatigue and its association with these factors in patients one year after severe COVID-19 hospital discharge.

METHODS: This cohort comprised participants aged 18-years and older diagnosed with COVID-19. Evaluations were conducted at one, four, six-, and twelve-months following hospital discharge. Clinical data were collected, which included assessments of fatigue - Functional Assessment of Chronic Illness Therapy Fatigue subscale, lung capacity ‒ Spirometry, physical performance - 1-minute Sit to Stand Test, psychological aspects - Hospital Anxiety and Depression Scale, and functional capacity - Barthel index.

RESULTS: Of the 162 participants, 50 % experienced fatigue one-month post-discharge and this prevalence gradually decreased to 36 % by the end of one-year period. The fatigue group had a median age of 58-years. It was predominantly composed of women, with a majority identifying as non-white and having a body mass index greater than 30 kg/m[2]. Physical performance assessments within the fatigue group showed no significant changes over time, whereas lung capacity demonstrated significant improvement only at the 12-month mark. Additionally, anxiety and depression levels were significantly higher in the fatigue group over time (p < 0.05).

CONCLUSIONS: Fatigue persisted in 36 % of participants one-year post-hospital discharge. The potential predictors of long-term fatigue were depressive symptoms and impaired lung function observed within the first month after hospital discharge. Therefore, the authors highlight the importance of screening and monitoring these aspects in order to enable early intervention in this population.},
}

@article {pmid41264615,
year = {2025},
author = {Uwakwe, CK and Rangan, ES and Kumar, S and Gutjahr, G and Miao, X and Brooks, AW and Maguire, P and Mishra, T and McGuire, L and Snyder, MP},
title = {Longitudinal wearable sensor data enhance precision of Long COVID detection.},
journal = {PLOS digital health},
volume = {4},
number = {11},
pages = {e0001093},
doi = {10.1371/journal.pdig.0001093},
pmid = {41264615},
issn = {2767-3170},
abstract = {Despite the millions of individuals struggling with persistent symptoms, Long COVID has remained difficult to diagnose due to limited objective biomarkers, often leading to underdiagnosis or even misdiagnosis. To bridge this gap, we investigated the potential of utilizing wearable sensor data to aid in the diagnosis of Long COVID. We analyzed longitudinal heart rate (HR) data from 126 individuals with acute SARS-CoV-2 infections to develop machine learning models capable of predicting Long COVID status using derived HR features, symptom features, or a combination of both feature sets. The HR features were derived across six analytical categories, including time-domain, Poincaré nonlinear, raw signal, Kullback-Leibler (KL) divergence, variational mode decomposition (VMD), and the Shannon energy envelope (SEE), enabling the capture of heart rate dynamics over various temporal scales and the quantification of day-to-day shifts in HR distributions. The symptom features used in the final models included chest pain, vomiting, excessive sweating, memory loss, brain fog, heart palpitations, and loss of smell. The combined HR- and symptom-feature model demonstrated robust predictive performance, achieving an area under the Receiver Operating Characteristic curve (ROC-AUC) of 95.1% and an area under the Precision-Recall curve (PR-AUC) of 85.9%. These values represent a significant improvement of approximately 5% in both the ROC-AUC and PR-AUC over the symptoms-only model. At the population level, this improvement in discrimination could lead to clinically meaningful reductions in misclassification and improved patient outcomes, achieved through a non-invasive diagnostic tool. These findings suggest that wearable HR data could be used to derive an objective biomarker for Long COVID, thereby enhancing diagnostic precision.},
}

@article {pmid41262872,
year = {2025},
author = {Lv, X and Ji, L and Cao, W and Xue, Y and Dai, H and Zhang, S},
title = {Revisiting lung cancer immunotherapy in the era of long COVID: mechanistic insights and therapeutic implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1657691},
pmid = {41262872},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/complications ; *Immunotherapy/methods ; *Lung Neoplasms/therapy/immunology ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; },
abstract = {In the post-COVID-19 era, understanding the long-term impact of Long COVID on the immune system is essential for deciphering its influence on lung cancer pathogenesis and immunotherapeutic efficacy. This review comprehensively examines how persistent COVID-19 sequelae-manifested as chronic inflammation, pulmonary fibrosis, cytokine dysregulation, and T-cell exhaustion can reshape the lung cancer microenvironment. In addition, the emerging roles of memory B cells and altered neutrophil function in promoting tumorigenesis are discussed. Importantly, we analyze recent clinical evidence suggesting that COVID-19 vaccination may enhance the efficacy of immune checkpoint inhibitors, potentially by modulating host immunity. By integrating mechanistic insights with clinical observations, this review aims to illuminate the challenges and opportunities at the intersection of Long COVID and lung cancer treatment, thereby fostering the development of personalized therapeutic strategies in the post-pandemic era.},
}

Humans
*COVID-19/immunology/complications
*Immunotherapy/methods
*Lung Neoplasms/therapy/immunology
SARS-CoV-2/immunology
Tumor Microenvironment/immunology
Immune Checkpoint Inhibitors/therapeutic use

@article {pmid41262358,
year = {2025},
author = {Goertzen, SM and Lindholm, DA and Walter, RJ and Huprikar, NA and Ganesan, A and Richard, SA and Mende, K and Harrell, TE and Peterson, PG and Simons, M and Tribble, DR and Agan, BK and Burgess, TH and Pollett, SD and Morris, MJ},
title = {Clinical, Radiographic, and Physiological Correlates of Post-COVID-19 Dyspnea in Military Health System Beneficiaries: Results From the Chronic Impairment With Pulmonary Symptoms (ChIPS) Sub-study.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf633},
pmid = {41262358},
issn = {2328-8957},
abstract = {BACKGROUND: Dyspnea has been described in up to 10-30% of patients post-SARS-CoV-2 infection. The underlying pathology for these persistent symptoms remains poorly understood. This study aimed to characterize changes in cardiopulmonary anatomical structure and physiology that may explain ongoing dyspnea after COVID-19.

METHODS: Participants had a history of symptomatic COVID-19, were between 18 and 65 years of age, and without significant pre-existing cardiopulmonary disease. Each participant underwent prospective chest high resolution computed tomography (HRCT), transthoracic echocardiography (TTE), electrocardiogram (ECG), pulmonary function testing (PFT) with lung volumes and diffusing capacity for carbon monoxide (DLCO), impulse oscillometry (IOS), and a six-minute walk test (6MWT) with Borg dyspnea scoring.

RESULTS: Among 115 enrolled participants, 39 had persistent dyspnea. The mean forced expiratory volume at 1 s/forced vital capacity (FEV1/FVC) ratio was higher in those with persistent dyspnea, but within normal ranges for both groups. There were no other statistically significant differences in FEV1, FVC, and DLCO between the groups. Those with ongoing dyspnea had a decreased walk distance (difference of 50.4 m, P = .01). Resting and post-6MWT Borg scores were 0.9 and 1.3 higher in those with persistent dyspnea, respectively (P-values <.001). There were no significant differences in IOS, HRCT, TTE, or ECG findings between groups.

CONCLUSIONS: This study demonstrated a difference in 6MWT distance and Borg scores between those with and without persistent dyspnea. There were no clear PFT, cardiac test, or HRCT findings that explained these persistent symptoms. Overall, this study demonstrates both subjective and objective differences between those with ongoing dyspnea following COVID-19 that are not explained by standard investigations typically ordered in clinical care for chronic dyspnea. These findings underscore the importance of further research into the etiology of post-COVID-19 dyspnea, including other investigations which may detect more subtle alterations in pulmonary physiology.},
}

@article {pmid41260143,
year = {2025},
author = {El Hajjar, AH and Zalaquett, Z and Rosenzveig, A and Syed, AB and Al-Dalakta, A and Majeed, Z and Villalonga, M and Ikram, J and Ehsan, M and Motairek, I and Heine, M and Berglund, F and Wang, TKM and Klein, A},
title = {Investigating Pericarditis Diagnosis in a Tertiary Pericardial Center: A Descriptive Study.},
journal = {JACC. Advances},
volume = {4},
number = {12 Pt 2},
pages = {102335},
doi = {10.1016/j.jacadv.2025.102335},
pmid = {41260143},
issn = {2772-963X},
abstract = {BACKGROUND: Pericarditis diagnosis can be challenging due to its nonspecific presentation, which may lead to frequent misdiagnosis.

OBJECTIVES: In this study, the authors aimed to report the rate of misdiagnosed pericarditis and describe the characteristics of these patients.

METHODS: Between September 2022 and September 2023, patients referred to the Pericardial Center with a diagnosis of pericarditis were enrolled in a prospective registry. Data were collected using a standardized history and physical examination template. Diagnosis was established according to the 2015 European Society of Cardiology guidelines. The prevalence of misdiagnosed pericarditis was calculated. Demographics, comorbidities, symptoms, laboratory results, and imaging were compared between the accurately diagnosed (group 1) and misdiagnosed pericarditis cohorts (group 2).

RESULTS: A total of 170 patients were included; the mean age was 49.1 years. Thirty-five percent of patients were misdiagnosed. Demographics were similar in both groups. Significant differences were found between group 1 and group 2) in coronary artery disease (17.3% vs 5.0%, P = 0.02), valvular disease (23.6% vs 8.3%, P = 0.01), and atrial fibrillation (24.5% vs 6.7%, P < 0.01). Significant late gadolinium enhancement on magnetic resonance imaging, raised inflammatory markers, electrocardiogram changes, and specific pericardial pain were more common in the accurately diagnosed group (P < 0.05). COVID-19 infection was significantly higher in the misdiagnosed group (16.7% vs 6.4%, P < 0.05), whereas cardiac surgery was significantly lower (3.3% vs 18.2%, P < 0.05).

CONCLUSIONS: Thirty-five percent of patients referred to the pericardial center are misdiagnosed with pericarditis. Inflammatory markers and late gadolinium enhancement on magnetic resonance imaging can help refine the diagnosis. COVID-19 infection is associated with higher rates of misdiagnosis.},
}

@article {pmid41259895,
year = {2025},
author = {Ben, ÂJ and Kisiangani, I and Kinya, I and Wynberg, E and de Jong, MD and Schultsz, C and Asiki, G and Vassall, A},
title = {Long-Term Changes in Health-Related Quality of Life and Economic Burden After a SARS-CoV-2 Infection: Analysis of the Long COVID Prospective Cohort Study in Nairobi.},
journal = {Value in health regional issues},
volume = {53},
number = {},
pages = {101545},
doi = {10.1016/j.vhri.2025.101545},
pmid = {41259895},
issn = {2212-1102},
abstract = {OBJECTIVES: To characterize long-term changes in health-related quality of life (HRQoL) and factors associated with catastrophic expenditures and catastrophic costs after a SARS-CoV-2 infection.

METHODS: Data from 291 participants of the Long COVID Prospective Cohort Study in Nairobi were analyzed. Participants were enrolled between 2022 and 2023 and followed up for 12 months. Possible factors and outcomes (HRQoL, catastrophic expenditures, and catastrophic costs) were measured every 3 months. Changes in outcomes over time were assessed using generalized estimating equations.

RESULTS: HRQoL was significantly reduced by 11.4% (95% CI -16.3% to -6.5%), 8.6% (95% CI -12.5% to -4.6%), 6.1% (95% CI -10.5% to -1.8%), and 4.1% (95% CI -7.9% to -0.3%) at 6, 9, 12, and 15 months after a positive polymerase chain reaction test, respectively, compared with the period before COVID-19. HRQoL was significantly reduced by 3.3% (95% CI -6.2% to -0.5%), and 10.9% (95% CI -16.5% to -5.3%), respectively, in participants with any COVID-19-related symptoms or fatigue. Older age (odds ratio [OR] 5.83, 95% CI 2.11 to 16.15), no COVID-19 vaccination (OR 5.83, 95% CI 2.11 to 16.15), any COVID-19-related symptoms (OR 2.22, 95% CI 1.15 to 4.28), and pay cut or reduced income due to COVID-19-related symptoms (OR 17.36, 95% CI 2.28 to 132.07) were associated with high odds of experiencing catastrophic expenditures. Severe/critical SARS-CoV-2 infection (OR 4.77, 95% CI 1.72 to 13.25) and fatigue (OR 2.27, 95% CI 1.03 to 4.96) significantly increased the odds of experiencing catastrophic costs, whereas better HRQoL (OR 0.12, 95% CI 0.02 to 0.57) and social support (OR 0.30, 95% CI 0.09 to 0.93) decreased the odds.

CONCLUSIONS: HRQoL remains reduced up to 15 months after a SARS-CoV-2 infection compared with pre-COVID-19 levels, with participants in better health and socioeconomic status less likely to experience catastrophic expenditures and catastrophic costs.},
}

@article {pmid41259457,
year = {2025},
author = {Hi, EMB and Bianchi, CCR and Gritte, RB and Klauss, PHA and Leal, NFSM and Oliveira, IS and Barros, MFCB and Soriano, FG and Curi, R and Machado, MCC},
title = {Detection of autoantibodies in severe COVID-19 patients two years after hospital discharge.},
journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica},
volume = {58},
number = {},
pages = {e14927},
doi = {10.1590/1414-431X2025e14927},
pmid = {41259457},
issn = {1414-431X},
mesh = {Humans ; *COVID-19/immunology/blood ; Middle Aged ; Male ; Female ; Aged ; *Autoantibodies/blood ; Adult ; Aged, 80 and over ; SARS-CoV-2/immunology ; Young Adult ; Biomarkers/blood ; Brazil ; Patient Discharge ; Procalcitonin/blood ; Antibodies, Antinuclear/blood ; C-Reactive Protein/analysis ; Case-Control Studies ; Rheumatoid Factor/blood ; Severity of Illness Index ; },
abstract = {After SARS-CoV-2 infection, severe COVID-19 may develop with persistent sequelae, even after hospital discharge. This condition may result from tissue damage or immune alterations caused by the virus, including immune dysregulation, hyperinflammation, loss of immune tolerance, excessive neutrophil extracellular trap (NET) production, and antibody cross-reactivity (molecular mimicry), which can promote autoantibody development. This study evaluated autoantibody expression in patients with long COVID-19 and its potential relationship with symptoms. Conducted in Baixada Santista, São Paulo, Brazil, the study involved 55 participants aged 21-85 years who had tested positive for SARS-CoV-2. Blood samples were collected two years post-discharge, and serum was analyzed for inflammatory and autoimmune markers, including antinuclear antibody (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), procalcitonin (PCT), Venereal Disease Research Laboratory test (VDRL), and C-reactive protein (CRP). Results were compared to a control group of 21 individuals who never tested positive for COVID-19. Among severe COVID-19 patients, 26 reacted to ANA, 16 to VDRL, 2 had elevated RF, 12 had increased PCT, and 11 had high CRP, whereas the control group showed no reactive results. Anti-CCP values were not significant. Findings suggest that hyperinflammation may contribute to autoimmunity, particularly in cases of reactive ANA levels, linking COVID-19 symptoms to autoimmune responses.},
}

Humans
*COVID-19/immunology/blood
Middle Aged
Male
Female
Aged
*Autoantibodies/blood
Adult
Aged, 80 and over
SARS-CoV-2/immunology
Young Adult
Biomarkers/blood
Brazil
Patient Discharge
Procalcitonin/blood
Antibodies, Antinuclear/blood
C-Reactive Protein/analysis
Case-Control Studies
Rheumatoid Factor/blood
Severity of Illness Index

@article {pmid41259430,
year = {2025},
author = {Braga, F and Espinosa, G and Monteiro, A and Milani, M and Paiva, J and Milani, JGPO and Franzoni, L and Stein, R and Cipriano, G and Gurgel, JL and Mourilhe-Rocha, R},
title = {Cardiopulmonary Resilience in Highly Active Individuals: Pre-Post COVID-19 Cardiopulmonary Exercise Testing Analysis.},
journal = {Arquivos brasileiros de cardiologia},
volume = {122},
number = {9},
pages = {e20250094},
doi = {10.36660/abc.20250094},
pmid = {41259430},
issn = {1678-4170},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; *Exercise Test/methods ; Female ; Retrospective Studies ; Adult ; Oxygen Consumption/physiology ; Middle Aged ; *Exercise Tolerance/physiology ; SARS-CoV-2 ; Time Factors ; },
abstract = {BACKGROUND: The COVID-19 pandemic has affected millions globally, with persistent impacts extending beyond the acute phase. One such effect is post-COVID (long COVID), characterized by symptoms such as fatigue and exercise intolerance lasting more than 60 days. Although regular exercise is associated with reduced risk of severe outcomes, reports of decreased athletic performance after COVID-19 - even among highly active individuals (HAIs) - have raised concerns regarding the long-term effects on physical health. Cardiopulmonary exercise testing (CPET) is a valuable tool to assess exercise intolerance and to investigate the metabolic and ventilatory consequences of COVID-19.

OBJECTIVES: To evaluate the impact of COVID-19 on cardiopulmonary function in HAIs by analyzing metabolic and ventilatory responses using CPET before and after infection.

METHODS: CPET data were retrospectively analyzed from HAIs of both sexes. Primary outcomes included changes in peak oxygen uptake (V ⋅ O2peak) and ventilatory efficiency (V ⋅ E/ V ⋅ CO2 slope). Statistical significance was set at 5% (p < 0.05).

RESULTS: A total of 43 HAIs (72.1% male; 44 ± 10 years) were included. The median interval between CPETs was 479 days, with testing performed a mean of 44 ± 27 days after COVID-19. V ⋅ O2peak decreased by a mean of 1.5 mL/kg/min (p = 0.017), representing a 3.84% reduction in predicted V ⋅ O2peak values (p = 0.045). V ⋅ E/ V ⋅ CO2 slope increased by 1.2 (p = 0.017).

CONCLUSION: Although HAIs are not immune to the effects of COVID-19, their high baseline physical activity levels appear to confer substantial cardiopulmonary resilience. Only minimal post-infection alterations were observed, which suggests that maintaining fitness may provide protective benefits against long-term sequelae of COVID-19.},
}

Humans
*COVID-19/physiopathology/complications
Male
*Exercise Test/methods
Female
Retrospective Studies
Adult
Oxygen Consumption/physiology
Middle Aged
*Exercise Tolerance/physiology
SARS-CoV-2
Time Factors

@article {pmid41256779,
year = {2025},
author = {Alemdaroğlu, E and Önal, R and Dizdar, D and Güler, T and Altaş, EU and Kutay Ordu Gökkaya, N},
title = {Continuous versus low-intensity interval aerobic exercise in pulmonary rehabilitation after COVID-19.},
journal = {Turkish journal of physical medicine and rehabilitation},
volume = {71},
number = {3},
pages = {385-394},
pmid = {41256779},
issn = {2587-1250},
abstract = {OBJECTIVES: This study aimed to compare the effectiveness of mild-moderate intensity continuous training (CT) and low-intensity interval moderate-intensity training (LIIT) aerobic exercises in pulmonary rehabilitation after coronavirus disease 2019 (COVID-19).

PATIENTS AND METHODS: This prospective study was conducted between January 2021 and January 2022. Sixty-three patients (47 males, 16 females; mean age: 54.3±11.3 years; range, 25 to 81 years) with one or more residual symptoms following COVID-19 infections were randomly included in the CT (n=33) or LIIT (n=30) groups. Fifteen sessions (60 min, 3-5/week) of aerobic exercise (20-min 40% of peak workload for CT; 40% peak workload with 3-min loaded and 1-min nonloaded intervals for LIIT, with 5 min warm-up and cool-down), breathing, and upper extremity strengthening exercises were applied. Outcome measures were symptom-limited submaximal exercise test, and six-minute walk test (6MWT), the modified Medical Research Council (mMRC) dyspnea scale, modified Borg dyspnea scale, and Borg 6-20 rate of perceived exertion scale, hand grip strength, fat-free mass, Hospital Anxiety and Depression Scale (HADS), and 36-item Short-Form Health Survey.

RESULTS: The maximum load and time reached during the exercise test, the 6MWT distance, hand grip strength, mMRC, HADS, and SF-36 scores significantly improved in both groups (p<0.05). Resting modified Borg dyspnea scores, heart rate, rate of perceived exertion, and oxygen supplementation requirement decreased significantly in the LIIT group (p<0.05). All posttreatment measures were similar in both groups (p>0.05). The changes in mMRC, resting heart rate, and 6MWT distance were significantly higher in the LIIT group compared to the CT group (p<0.05).

CONCLUSION: Both CT and LIIT improved functional capacity, dyspnea, tachycardia, depression, and quality of life measures safely and effectively in COVID-19 survivors with residual symptoms. Patients with poor clinical status who cannot tolerate CT after an acute pulmonary condition such as COVID-19 may benefit from LIIT.},
}