@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.},
}

@article {pmid41256693,
year = {2025},
author = {Arish, M and Chaudhuri, AS and Tang, J and Narasimhan, H and Fang, A and Tang, J and Wei, X and Li, C and Cheon, IS and Qian, W and Naz, F and Almeida-Santos, G and Young, SP and Parimon, T and Shim, YM and Vassallo, R and Chen, P and Sun, J},
title = {Targeting a macrophage stemness factor to mitigate diseases post respiratory viral infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.03.680366},
pmid = {41256693},
issn = {2692-8205},
abstract = {Tissue-resident alveolar macrophages (AMs) rely on intrinsic stem-like programs for self-renewal and maintenance, yet the transcriptional networks that support these functions and their relevance to post-viral lung disease remain largely unknown. Here, we identify TCF4 (Tcf7l2) as a critical transcription factor that governs AM maturation and stemness. Loss of TCF4 impaired AM proliferation, shifted their identity toward a pro-inflammatory phenotype, and exacerbated host morbidity following influenza or SARS-CoV-2 infection. Conversely, enforced TCF4 expression promoted the expansion of mature AMs, and supported lung recovery, thereby protecting against severe acute viral disease. Mechanistically, TCF4 antagonized β-catenin-driven inflammatory transcription while preserving oxidative phosphorylation, defining a reciprocal regulatory axis essential for AM function. Notably, respiratory viral infections and exuberant interferon signaling suppressed TCF4 expression, which remains chronically reduced in murine and human lungs with post-COVID fibrosis. This downregulation is associated with persistent KRT8 [hi] dysplastic epithelium and collagen deposition. Moreover, aging diminished TCF4 levels and enforced TCF4 expression dampened age-associated decline of AM self-renewal. Furthermore, in vivo TCF4 overexpression after viral clearance enhanced mature AM accumulation, promoted lung epithelium regeneration, attenuated chronic tissue fibrosis and restored pulmonary physiologial function in aged lungs in a model of persistent pulmonary fibrosis post-acute viral infection. These findings have established TCF4 as a key regulator of AM stemness and identified a promising therapeutic target for long COVID and related chronic lung diseases through the modulation of embryonic-derived macrophage regenerative capacity by targeting TCF4.},
}

@article {pmid41255761,
year = {2025},
author = {Sularea, VM and Townsend, L and Reid, C and Atanasescu, AV and Dyer, AH and Giangrazi, F and Lawrence, RR and Sivan, M and Moran, B and Doherty, DG and Conlon, NP and Long, A and O'Farrelly, C},
title = {Digitally Assessed Long COVID Symptomatology Is Associated With Lymphocyte Mitochondrial Dysfunction and Altered Immune Potential.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf447},
pmid = {41255761},
issn = {2328-8957},
abstract = {BACKGROUND: Postacute sequelae of SARS-CoV-2 infection, also known as long COVID (LC), is a complex and heterogenous condition affecting millions worldwide with a poorly understood underlying pathology. Although metabolic dysregulations have been described in LC, it remains unclear whether circulating immune cells exhibit immunometabolic alterations.

METHODS: We conducted a detailed clinical, immunologic, and mitochondrial analysis on 27 patients with LC and 27 who recovered from COVID-19 and were healthy. Symptom burden and severity were assessed and quantified via a digital platform with the modified COVID-19 Yorkshire Rehabilitation Scale. Mitochondrial function of circulating immune cell populations (lymphocytes and monocytes) was analyzed by measuring mitochondrial mass and mitochondrial membrane potential. Production of 11 cytokines after whole blood stimulation with bacterial and viral agonists was measured by multiplex immunoassay. Relationships between mitochondrial and immune parameters with LC symptoms were investigated.

RESULTS: Patients with LC exhibited significant symptom burden, with worsening across all symptom domains as compared with their health state before SARS-CoV-2 infection. They also had a decreased mitochondrial membrane potential of CD56[bright] natural killer cells, particularly in patients experiencing dizziness, whereas reduced mitochondrial membrane potential in CD4+ lymphocytes was found in patients with worsening breathlessness. Upon LPS stimulation, patients with LC demonstrated significantly lower IFN-γ production. In response to viral ligand R848, impaired IFN-β and IL-10 responses were associated with worsening cough and executive functions.

CONCLUSIONS: Symptom severity in LC is associated with immune cell mitochondrial dysfunction and altered cytokine responses, highlighting potential disease biomarkers and targets for future therapeutic strategies.},
}

@article {pmid41254881,
year = {2025},
author = {Kartal Öztürk, G and Böncüoğlu, E and Kıymet, E and Şahinkaya, Ş and Cem, E and Yılmaz Çelebi, M and Kara, AA and Karkıner, CŞ and Bayram, SN and Devrim, İ},
title = {Long-term follow-up of children after COVID-19 infection and monitoring pulmonary functions.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {67},
number = {1},
pages = {e70274},
doi = {10.1111/ped.70274},
pmid = {41254881},
issn = {1442-200X},
mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; Child ; Male ; Female ; Adolescent ; Follow-Up Studies ; Respiratory Function Tests ; Child, Preschool ; Infant ; Prospective Studies ; *Lung/physiopathology ; },
abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus 2 is now part of our lives. Many children still experience post-COVID respiratory conditions and require evaluation and follow-up.

METHODS: Children referred to the Pediatric Pulmonology Department between 2021 and 2022, due to a history of COVID-19 pneumonia with/without comorbid disease and respiratory complaints after COVID-19, were prospectively followed up with pulmonary function tests at 3, 6, and 12 months.

RESULTS: The median age of 138 children was 14 years (1-18), 42 (30.4%) had comorbid conditions, and 40 (28.9%) had a history of COVID-19 pneumonia. Respiratory symptoms after infection persisted in approximately 62% of children, and 28% of children who had no symptoms before infection were diagnosed with asthma (N = 18, 13%), allergic rhinitis (N = 5), anxiety and tic disorder (N = 4), and other diseases (N = 4). At admission, pulmonary function abnormalities were detected in 12% (N = 4 obstructive ventilatory pattern, N = 6 restrictive, and N = 2 mixed). Pulmonary functions were similar in children with and without persistent respiratory complaints (PRCs). At the 12-month follow-up, there were three children (2.1%) with PRC, and pulmonary function anomalies persisted in five children. A significant increase in pulmonary function was observed in both children with and without PRC. FEF25-75, the indicator of small airways, was lower in children with PRC.

CONCLUSIONS: This study suggested that COVID-19 may have affected pulmonary function in children independently of respiratory symptoms and that this effect may be more severe in children with PRC. It is necessary to follow up and research examination and early intervention methods for post-COVID conditions.},
}

Humans
*COVID-19/complications/physiopathology/epidemiology
Child
Male
Female
Adolescent
Follow-Up Studies
Respiratory Function Tests
Child, Preschool
Infant
Prospective Studies
*Lung/physiopathology

@article {pmid41254361,
year = {2025},
author = {Stiles, LE and Larsen, NW and Eastin, EF and Miglis, MG},
title = {Response to letter by Zadeh et al. regarding "Chronic autonomic symptom burden in long-COVID: a follow-up cohort study".},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {},
number = {},
pages = {},
pmid = {41254361},
issn = {1619-1560},
}

@article {pmid41253410,
year = {2025},
author = {Volckaerts, T and Ruttens, D and Quadflieg, K and Burtin, C and Cops, D and De Soomer, K and Roelant, E and Verhaegen, I and Daenen, M and Criel, M and Vissers, D and Lapperre, T},
title = {Improved functional exercise capacity after primary care pulmonary rehabilitation in patients with long COVID (PuRe-COVID): a pragmatic randomised controlled trial.},
journal = {BMJ open respiratory research},
volume = {12},
number = {1},
pages = {},
doi = {10.1136/bmjresp-2025-003653},
pmid = {41253410},
issn = {2052-4439},
mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/rehabilitation/physiopathology/complications ; *Exercise Tolerance/physiology ; Primary Health Care ; Adult ; Walk Test ; SARS-CoV-2 ; *Exercise Therapy/methods ; Aged ; Hand Strength ; Treatment Outcome ; Fatigue ; Dyspnea ; Patient Reported Outcome Measures ; },
abstract = {BACKGROUND: Pulmonary rehabilitation (PR) improves physical status and symptoms in patients with long COVID, but access to specialised hospital-based centres is challenging. This trial studied the effect of primary care PR on functional exercise capacity and symptoms in patients with long COVID.

METHODS: In this pragmatic randomised controlled trial (PuRe-COVID), patients with long COVID were randomised to a 12-week stepwise PR programme in primary care, or to a control group without PR. The primary end point was change in 6 min walk distance (6MWD) from baseline to 12 weeks. Additional outcomes, measured at 6, 12, 24 and 36 weeks, included patient-reported outcomes, physical activity, maximal inspiratory (MIP) and expiratory pressures and hand grip strength.

RESULTS: In total, 76 patients were randomised (PR/control group (n=39/37); mean age 49±13 years). The change in 6MWD at 12 weeks was estimated to be +39 m in the PR group compared with the control group (95% CI (18 to 59), p<0.001). Furthermore, a decrease in Checklist Individual Strength (CIS)-fatigue was found for the PR group (-6 points; 95% CI (-10 to -2), p=0.011). At 12 weeks, patients in the intervention group were more likely to have a clinically significant improvement in 6MWD (OR 5.7, 95% CI (2.0 to 16.1), p=0.001), CIS-fatigue (OR 3.8, 95% CI (1.2 to 12.0), p=0.020), MIP (OR 3.7, 95% CI (1.05 to 12.7), p=0.036) and modified Medical Research Council dyspnoea score (OR 5.2, 95% CI (1.6 to 16.4), p=0.003).

CONCLUSIONS: Primary care stepwise individual PR may improve functional exercise capacity, fatigue and dyspnoea in patients with long COVID. It therefore may be a promising treatment option in primary care for patients with long COVID experiencing fatigue and/or respiratory symptoms.

TRIAL REGISTRATION NUMBER: NCT05244044.},
}

Humans
Male
Female
Middle Aged
*COVID-19/rehabilitation/physiopathology/complications
*Exercise Tolerance/physiology
Primary Health Care
Adult
Walk Test
SARS-CoV-2
*Exercise Therapy/methods
Aged
Hand Strength
Treatment Outcome
Fatigue
Dyspnea
Patient Reported Outcome Measures

@article {pmid41253056,
year = {2025},
author = {Ouyang, T and Huang, Z and Wei, S and Yang, J and Voskrebenzev, A and Vogel-Claussen, J and Guo, S and Yang, Q},
title = {Longitudinal assessment of pulmonary perfusion and ventilation defects in long COVID: A one-year study using phase-resolved functional lung (PREFUL) MRI.},
journal = {Computers in biology and medicine},
volume = {199},
number = {},
pages = {111316},
doi = {10.1016/j.compbiomed.2025.111316},
pmid = {41253056},
issn = {1879-0534},
abstract = {RATIONALE AND OBJECTIVES: The long-term trajectories of pulmonary perfusion and ventilation after recovery from SARS-CoV-2 infection are lacking. This study aims to longitudinally assess changes in perfusion (QDP) and ventilation (VDP) defects using phase-resolved functional lung (PREFUL) MRI in post-SARS-CoV-2 infection.

MATERIALS AND METHODS: This prospective study was conducted from January to May 2023 and included non-hospitalized, COVID-19-positive patients with pneumonia or symptoms suggestive of pneumonia, as well as healthy controls. Serial MRI scans were performed at acute, 3, 6, and 12 months after symptom onset, and healthy controls underwent only one MRI scan. Longitudinal comparisons of QDP and VDPCombined were employed by linear mixed-effects models. Long COVID was defined as persistent SARS-CoV-2 symptoms for at least three months, with associated factors identified through logistic regression.

RESULTS: A total of 60 participants (median age 68.5 years; 30 female) were included. VDPCombined was 21 %, 18 %, 16 %, and 13 % at the acute phase, 3 months, 6 months, and 12 months, respectively, with a significant difference observed in the longitudinal comparison (P = 0.034). Moreover, at 12 months, VDPCombined showed no significant difference compared to the healthy control (P = 0.280). QDP also decreased (42 %, 36 %, 35 %, and 19 % at acute, 3 months, 6 months, and 12 months, respectively; P < 0.001), but remained significantly higher than in healthy controls at 12 months (P < 0.001). At follow-up, 55 % of participants (33 of 60) had long COVID, with higher acute-phase QDP associated with increased odds of developing long COVID (odds ratio, 1.20; P = 0.001).

CONCLUSION: Pulmonary perfusion impairment persists up to 12 months following SARS-CoV-2 infection. Severe perfusion defects during acute phase are a risk factor for the development of long COVID.},
}

@article {pmid41252855,
year = {2025},
author = {Oh, S and Wijaya, J},
title = {Predictive surveillance and diagnosis of COVID-19: An integrative machine learning and wastewater multi-omics approach.},
journal = {Water research},
volume = {289},
number = {Pt B},
pages = {124981},
doi = {10.1016/j.watres.2025.124981},
pmid = {41252855},
issn = {1879-2448},
abstract = {COVID-19 has had major global impacts, highlighting the importance of robust predictive surveillance and diagnostic systems to ensure effective public health responses. Traditional surveillance methods based on passive case counting and diagnostic testing of individual patients often suffer from delays and resource constraints, preventing timely responses. This study proposed an integrative framework integrating machine learning (ML)-derived predictive surveillance with wastewater-based diagnosis, aiming to predict temporal trends in Korea and identify disease-causing agents. The ML model utilized crowdsourced COVID-19-related keywords, climatic, and environmental data, optimized via model selection and feature selection. The integrated data-driven model predicted COVID-19 cases over three years more accurately than those using single source data (i.e., baseline model). The explainable AI technique (i.e., helping to inform how the model made those predictive decisions) identified six keywords (reducing phlegm, throat pain, long COVID-19, sore throat, COVID-19 self-kit, and COVID-19 kit) as robust predictors of disease trends. In a proof-of-concept experiment, wastewater-based genotyping of disease-causing agents and affected human communities in sewershed areas was conducted. Metatranscriptomics of municipal wastewater was conducted to identify COVID-19 viral variants, evolutionarily related to those clinically isolated strains, distinguishable from conventional diagnostic testing of individual patients. Wastewater-derived metagenomics was also performed to assess genomic variation in the affected human populations. The integrative framework proposed in this study offers a rapid, cost-effective approach for the surveillance and diagnosis of COVID-19 and other infectious diseases, thus strengthening or complementing existing health systems.},
}

@article {pmid41249654,
year = {2025},
author = {Azola, A and Dastgheyb, RM and Easter, R and Parker, H and Della Penna, C and Santiuste, I and Schultz, H and Ehrenspeck, A and Veenhuis, R and Rubin, LH},
title = {Putting the PASC Score to the Test: Clinical vs. Statistical Accuracy in Long COVID Diagnosis.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41249654},
issn = {1525-1497},
support = {RF1 MH133411/MH/NIMH NIH HHS/United States ; },
abstract = {OBJECTIVE: To validate the RECOVER Post-Acute Sequelae of SARS-CoV-2 infection (PASC) score in a cohort of patients who develop long COVID (LC) or fully recover while iteratively improving the tool's sensitivity and specificity.

METHODS: A cross-sectional study in 130 LC patients followed at LC clinics in Baltimore, MD, USA, who met the National Academies of Sciences, Engineering, and Medicine (NASEM) 2024 LC definition, and 60 SARS-CoV-2 exposed but fully recovered individuals. LC participants were required to have at least one neuropsychiatric symptom. Participants completed comprehensive surveys and questionnaires assessing symptoms based on published methods to determine PASC score. Using the NASEM 2024 LC definition as the "true" condition, we compared evaluation metrics for the RECOVER PASC score cutoff (PASC > 12) and the presence of individual/multiple symptoms. Evaluation metrics (e.g., sensitivity, specificity, F1) were calculated based on these classifications for the overall PASC score and symptom combinations.

RESULTS: The LC cohort (n = 130) had a mean age of 47.2 years and was predominantly female (72%), White (79%), and well-educated (77% > 16 years). Controls (n = 60) were similar demographically. LC diagnosis and PASC scores were significantly associated (χ[2] = 102.99, P < 0.001). The PASC score showed excellent specificity (100%) and positive predictive value (PPV; 100%) albeit limited sensitivity (80%), missing 20% of participants with LC. We found that loss of smell/taste, post-exertional malaise, or lack of sexual desire or capacity demonstrated 94% sensitivity, 92% specificity, and 96% PPV, 87% NPV, and an F1 score of 0.949.

CONCLUSION: Validation of the RECOVER PASC supports its utility and highlights the need for ongoing refinement of the LC definition. We call for national efforts to develop readily implementable clinical tools for LC diagnosis.},
}

@article {pmid41249484,
year = {2025},
author = {Eisinger, RW and Breen, JJ and Beigel, J and Geerling, E and Gerberding, J and Taubenberger, JK},
title = {Progress on the pathway to long COVID treatments.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {41249484},
issn = {1529-2916},
}

@article {pmid41249167,
year = {2025},
author = {Thaweethai, T and Donohue, SE and Martin, JN and Hornig, M and Mosier, JM and Shinnick, DJ and Ashktorab, H and Atieh, O and Blomkalns, A and Brim, H and Chen, Y and Cortez, MM and Erdmann, NB and Flaherman, V and Goepfert, P and Goldman, JD and Hamburg, NM and Han, JE and Heath, JR and Jacoby, V and Jolley, SE and Kelly, JD and Kelly, SW and Kim, C and Krishnan, JA and Letts, R and Levitan, EB and Modes, ME and McComsey, GA and Metz, TD and Mullington, JM and Ofotokun, I and Okumura, MJ and Paredes, CC and Patterson, TF and Peluso, MJ and Reece, R and Sherif, ZA and Simhan, HN and Simmons, C and Singh, U and Taylor, BS and Taylor, BD and Trinity, JD and Troxel, AB and Utz, PJ and Vasey, AJ and Weinberger, E and Wiley, Z and Wisnivesky, J and Yee, LM and Horwitz, L and Foulkes, AS and Levy, BD and , },
title = {Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9557},
pmid = {41249167},
issn = {2041-1723},
support = {OTA OT2HL161841, OT2HL161847, OT2HL156812, OT2HL162087, and R01 HL162373//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *COVID-19/epidemiology/physiopathology/virology ; Female ; Male ; United States/epidemiology ; Adult ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; Longitudinal Studies ; Aged ; Post-Acute COVID-19 Syndrome ; },
abstract = {Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.},
}

Humans
*COVID-19/epidemiology/physiopathology/virology
Female
Male
United States/epidemiology
Adult
Middle Aged
Prospective Studies
SARS-CoV-2
Longitudinal Studies
Aged
Post-Acute COVID-19 Syndrome

@article {pmid41248356,
year = {2025},
author = {Nejatinamini, S and Charlton, C and Harman, S and Kanji, JN and Kellner, JD and Lines, K and Murdoch, K and Powell, W and Roberts, J and Rosner, W and Shen-Tu, G and Tipples, G and Xu, JY and Vena, JE},
title = {COVID-19 antibody testing study: a nested substudy within Alberta's Tomorrow Project (ATP) in Alberta, Canada.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e101336},
doi = {10.1136/bmjopen-2025-101336},
pmid = {41248356},
issn = {2044-6055},
mesh = {Humans ; Alberta/epidemiology ; Middle Aged ; *COVID-19/epidemiology/diagnosis/immunology ; Female ; Male ; Adult ; Aged ; Prospective Studies ; *SARS-CoV-2/immunology ; *Antibodies, Viral/blood ; *COVID-19 Serological Testing ; Longitudinal Studies ; },
abstract = {PURPOSE: The Alberta's Tomorrow Project (ATP) prospective cohort study was established in 2000 to investigate the causes of cancer and chronic disease. The cohort consists of almost 55 000 participants aged 35-69 years at the time of recruitment. From 2020 to 2022, ATP conducted a longitudinal substudy, the COVID-19 Antibody Testing (CAT) study, nested in this existing cohort, to understand the spread and impact of the SARS-CoV-2. In this cohort profile, we describe the CAT study design, recruitment and initial findings.

PARTICIPANTS: In this prospective cohort substudy, ~4000 participants completed online surveys and provided blood samples at a study centre every 4 months for 1 year, across four cities in Alberta, Canada. The study was launched on a rolling basis beginning in September 2020 and data collection was completed in May 2022. The surveys collected information on health and lifestyle factors, COVID-19 (testing, symptoms, vaccination, public health recommendations) and impacts of the pandemic (including economic, health services, mental health). Blood samples were tested for antinucleocapsid and antispike protein SARS-CoV-2 antibodies.

FINDINGS TO DATE: A total of 4102 participants consented and attended a study centre at baseline, and almost 90% of these completed the study. Overall, participants were aged 61±10 years, 60% female, 12% came from rural areas, 45% had at least a bachelor's degree, 24% reported a household income <$C75 000 and 39% were retired. About 15% of participants tested positive for antibodies induced by a SARS-CoV-2 infection over the course of the study, and about 18% of those who were infected reported long COVID (persistent symptoms for >4 weeks). By the end of the study, 96% of participants had received at least one COVID-19 vaccine dose. Through investigating other outcomes, it was observed that participants under 50 years of age were more likely to be assessed to have mild or moderate-to-severe anxiety and depressive symptoms compared with older participants. In addition, approximately 15% of participants reported a moderate to major impact on their ability to meet financial obligations.

FUTURE PLANS: Serology results, together with health, lifestyle and sociodemographic data, and the continued follow-up of these participants as part of the broader ATP cohort study (planned through 2065), will provide opportunities to investigate the long-term sequelae of COVID-19 infection as well as the broader impacts of the pandemic on physical, mental and emotional health. Data are available to researchers on request through the ATP access process.},
}

Humans
Alberta/epidemiology
Middle Aged
*COVID-19/epidemiology/diagnosis/immunology
Female
Male
Adult
Aged
Prospective Studies
*SARS-CoV-2/immunology
*Antibodies, Viral/blood
*COVID-19 Serological Testing
Longitudinal Studies

@article {pmid41248018,
year = {2025},
author = {Wu, J and Xie, N and Meng, W and Ma, Y and Li, Z and Zeng, H and Chen, Y},
title = {Long COVID and symptom persistence in post-discharge omicron patients: Insights into C-reactive protein.},
journal = {Chronic illness},
volume = {},
number = {},
pages = {17423953251387913},
doi = {10.1177/17423953251387913},
pmid = {41248018},
issn = {1745-9206},
abstract = {ObjectivesLong-term health effects of Omicron infection, particularly persistent Long COVID in hospitalized patients, require further investigation.MethodsPatients hospitalized for Omicron infection (Dec 2022-Mar 2023) underwent follow-ups at 6 months and 1 year post-discharge. Univariate/multivariate analyses identified mortality predictors, symptom trends, and optimal CRP levels (mg/L) thresholds.ResultsAmong 410 patients, 59 died; mortality predictors included age (OR = 1.070), ICU admission (OR = 15.748), diabetes (OR = 3.363), antibacterial use (OR = 0.283), and lymphocyte count (OR = 0.099). At 6 months, 86.0% reported ≥1 symptom (83.5% at 1 year). Fatigue, cough, and snoring were most common, with symptom counts decreasing significantly over time. Symptomatic patients had longer hospital stays (P = 0.022), lymphopenia (P = 0.036), and elevated CRP levels (P = 0.010). A CRP level ≥15.38 mg/L was associated with a greater risk of symptom persistence and may serve as a potential predictive marker.ConclusionHospitalized Omicron survivors experience prolonged symptoms, with ICU admission, age, and diabetes as key mortality risks. Fatigue and snoring may persist despite overall improvement. Elevated CRP and prolonged hospitalization in symptomatic patients underscore the need for long-term monitoring and interventions targeting high-risk groups.},
}

@article {pmid41247781,
year = {2025},
author = {Henrich, TJ and Montgomery, CP and Graf, J and Ismali, N and Mohandas, S and Suthar, MS and Brim, H and Coffin, JM and Pagaria, A and Guzmán Rivera, J and Vudali, U and Keim, P and Zhong, G and McGrath, R and Edwards, B and García-Sastre, A and Gennaro, ML},
title = {The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
doi = {10.7554/eLife.106308},
pmid = {41247781},
issn = {2050-084X},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; *Coinfection/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Bacterial Infections/complications ; },
abstract = {A major health challenge resulting from the COVID-19 pandemic is the manifestation of post-acute sequelae of SARS-CoV-2 (PASC). PASC (or long COVID) is a collective term used for clinical symptoms, various pathologies, and life-quality-changing functional impairment that persist for months to years after the initial SARS-CoV-2 infection. The mechanisms underlying PASC are not understood, although advances have been made in identifying factors that may contribute to long-term pathology. Recent data have emerged, showing an association between SARS-CoV-2 viral persistence and non-SARS-CoV-2 infections (pre-existing, viral reactivation, or new infections) in facilitating or mediating PASC. However, the heterogeneous nature and timing of co-infections have made it challenging to understand, interpret, and contextualize their contribution to PASC. Here, we summarize the impact of potential viral, bacterial, and fungal infections on SARS-CoV-2 pathogenesis, with a focus on their possible roles in the development of PASC. We also provide a framework to understand the mechanisms of PASC and inform basic, translational, and clinical research initiatives, including RECOVER, a large and ongoing research initiative to understand, treat, and prevent long COVID.},
}

Humans
*COVID-19/complications/pathology/virology
*Coinfection/virology
*SARS-CoV-2
Post-Acute COVID-19 Syndrome
Bacterial Infections/complications

@article {pmid41245391,
year = {2025},
author = {Duarte, ACB and Lafetá, ML and Verrastro, CGY and Mancuso, FJ and Tanni, SE and Albuquerque, ALP and Sperandio, PA and Oliveira, RKF and Ota-Arakaki, JS and Ferreira, EVM},
title = {Chronic Dyspnea and Residual Pulmonary Vascular Sequelae After COVID-19 Pulmonary Embolism: A Retrospective Analysis.},
journal = {Pulmonary circulation},
volume = {15},
number = {4},
pages = {e70198},
doi = {10.1002/pul2.70198},
pmid = {41245391},
issn = {2045-8932},
abstract = {During the COVID-19 pandemic, Brazil was one of the most affected countries. Patients presented higher risk of acute venous thromboembolism (VTE), in particular, pulmonary embolism (PE). However, long-term implications of these events remain unknown. A retrospective analysis from the FENIX study was conducted, and patients with COVID-19-related VTE during hospitalization were included. Further analysis, up to 6 months after the acute event, was performed exclusively in patients with PE. Persistence of dyspnea and exercise intolerance was evaluated through imaging, rest, and exercise functional tests. Cumulative incidence of VTE during hospitalization among COVID-19 survivors followed at the outpatient clinic was 17.7% (n = 75/423) and of acute PE was 9.9% (n = 42/423). Patients with PE were mostly male (66%), 56 ± 16 years old, and mainly classified as intermediate-low risk (74%). Dyspnea (mMRC≥ 1) up to 6 months of PE was present in 56% (n = 19/34), with a borderline association with parenchymal lung sequelae on chest CT scan (p = 0.069). Symptomatic patients upon follow-up presented lower FEV1 and FVC, as well as increased peak VD/VT ratio and ventilatory inefficiency. No signs of pulmonary hypertension (PH) were identified on echocardiogram (ECHO) and cardiopulmonary exercise testing (CPET). Persistence of dyspnea among post-PE related to COVID-19 was high. However, no cases of PH were found; follow-up findings may be related to pulmonary parenchymal and microvascular injury. Also, we cannot exclude association with long-COVID, in which pathophysiological mechanisms are multifactorial, involving chronic inflammatory changes and multiorgan dysfunction, highlighting the need for comprehensive evaluation of exercise intolerance through invasive CPET.},
}

@article {pmid41245100,
year = {2025},
author = {Ramachandran, R and Sathar, F and Mokome, P and Mathabela, N and Mahlase, E and Charalambous, S and Rachow, A and Glover, NA and Ivanova, O},
title = {Acceptability and feasibility of a group intervention for long COVID in Johannesburg, South Africa: a mixed-method study.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1666387},
doi = {10.3389/frhs.2025.1666387},
pmid = {41245100},
issn = {2813-0146},
abstract = {BACKGROUND: COVID-19 affected 777 million people globally, with 7.1 million deaths. In Africa, 9.6 million cases and 176,000 deaths were reported. Long COVID, a significant consequence of the COVID-19, presented by chronic symptoms, affects the physical and mental health, thereby impacting the quality of life. While high-income countries implemented rehabilitation programs for managing long COVID symptoms, low- and middle-income countries faced healthcare disparities. In South Africa, limited multidisciplinary interventions were evident. This study aimed to assess the acceptability and feasibility of an 8-week rehabilitation and self-management program for long COVID using mixed-methods approach in Johannesburg.

METHODS: Patients and hospital staff who suffered from at least one symptom of long COVID for a period of two months and who consented to participate in the intervention were recruited from Tembisa Provincial Tertiary Hospital. The recruitment was from July to October 2023. Questionnaires were administered and interviews with selected participants were conducted to assess the acceptability and feasibility of the intervention. A descriptive analysis was carried out for the quantitative data, and a deductive thematic analysis was used for the interviews.

RESULTS: The participants had positive perceptions towards the design of the intervention, delivery, materials used and support by research staff and external consultants such as dietitians, physiotherapists, and psychologists. The participants stated that the intervention had improved their knowledge of long COVID and increased their self-confidence. Major barriers related to the intervention perceived by the participants were infrastructure, time and language. Recommendations from the participants included expanding the intervention at the community level and extending the duration of the intervention beyond 8-weeks.

CONCLUSION: This pilot intervention, that aimed to manage the symptoms of long COVID, was well accepted by the participants and achieved its intended outcome. Similar interventions are required at the clinical as well as community levels.},
}

@article {pmid41244103,
year = {2025},
author = {Yue, Y and Han, X and Chen, Q and Dai, L and Ai, Q and Zhang, Z and Ma, F and Gao, J},
title = {The effect of pulmonary rehabilitation for post-acute sequelae of SARS-CoV-2 infection in patients: a systematic review and meta-analysis.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1634351},
doi = {10.3389/fresc.2025.1634351},
pmid = {41244103},
issn = {2673-6861},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, are characterized by persistent symptoms such as fatigue, dyspnea, and reduced functional capacity. Pulmonary rehabilitation (PR) is recommended for chronic respiratory conditions, but its effectiveness in PASC, particularly across different delivery modes, remains uncertain.

OBJECTIVE: To assess the impact of PR, including telerehabilitation and in-person modalities, on physical function, dyspnea, pulmonary function, fatigue, and quality of life in patients with PASC.

METHODS: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science from inception to March 25 for controlled clinical trials assessing the effects of PR in PASC patients. Two independent reviewers performed study selection and data extraction. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and data were analyzed using Review Manager (RevMan) 5.4.1. Effect sizes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI).

RESULTS: Ten randomized controlled trials involving 673 participants were included. Most studies were judged to have a moderate risk of bias. Compared with usual care, PR significantly improved six-minute walk distance (MD: 76.85 meters; 95% CI: 57.35-96.36; p < 0.001), maximal inspiratory pressure (MD: 17.63 cmH₂O; 95% CI: 4.50-30.76; p = 0.009), fatigue (SMD: -1.15; 95% CI: -1.83 to -0.48; p < 0.001), and quality of life (SMD: 1.73; 95% CI: 0.56-2.91; p = 0.004). No statistically significant improvement was found for dyspnea (MD: -0.41; 95% CI: -1.51 to -0.68; p = 0.46). Subgroup analyses showed no significant differences between telerehabilitation and in-person PR across all outcomes, including exercise capacity (p = 0.84), dyspnea (p = 0.86), fatigue (p = 0.93), and quality of life (p = 0.44).

CONCLUSIONS: PR improves physical and functional outcomes in patients with PASC. Telerehabilitation offers a clinically equivalent alternative to in-person PR, supporting its broader implementation.},
}

@article {pmid41242093,
year = {2025},
author = {Alonso-Domínguez, J and González-Nóvoa, JA and López-López, A and Martínez-Barros, I and Pérez-González, A and Leiro-Fernández, V and Aguayo-Arjona, J and Teijeira, S and Veiga, C and Poveda, E},
title = {Artificial intelligence-based identification of key risk factors for long COVID from early clinical data.},
journal = {Journal of infection and public health},
volume = {19},
number = {1},
pages = {103051},
doi = {10.1016/j.jiph.2025.103051},
pmid = {41242093},
issn = {1876-035X},
abstract = {INTRODUCTION: Long COVID, a complex condition characterized by persistent symptoms following SARS-CoV-2 infection, has become a significant public health concern. Early identification of individuals at risk for long COVID is crucial for effective management. This study explores the potential of biochemical and clinical markers, alongside machine learning (ML) models, to predict long COVID development using data from the first 72 h post-admission.

METHODS: We analyzed clinical and laboratory data from 394 individuals diagnosed with SARS-CoV-2. A predictive model for long COVID was developed using machine learning algorithms, particularly XGBoost, to identify key biomarkers associated with the development of long COVID symptoms at 3 months post-infection. The model hyperparameters were optimized using Bayesian optimization techniques, and variable importance was assessed using SHAP values.

RESULTS: The predictive model achieved an area under the receiver operating characteristic curve (AUC-ROC) of 0.732, indicating moderate discriminatory power. Key variables identified included hemoglobin levels, oxygen saturation, weight, C-reactive protein (CRP), activated partial thromboplastin time (APTT), sodium, type of pulmonary infiltrates, and sex. Hemoglobin levels were the only statistically significant variable (p = 0.015) between those who developed long COVID and those who did not. Despite these findings, the model showed moderate overall accuracy (63.9 %) but excelled in recall (78.6 %), highlighting its potential in clinical settings for early identification of high-risk patients.

CONCLUSIONS: Our study demonstrates the feasibility of using machine learning to predict long COVID based on early clinical and laboratory data. While individual biomarkers alone may have limited predictive value, their combination enhances risk assessment for long COVID. Future studies should focus on refining the model and validating it in broader populations, including those with milder COVID-19 forms, to improve its accuracy and clinical utility.},
}

@article {pmid41241149,
year = {2025},
author = {Park, WH},
title = {The Mitochondrial Nexus: Dysfunction, Inhibition, and Therapeutic Frontiers in Lung Disease.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108506},
doi = {10.1016/j.rmed.2025.108506},
pmid = {41241149},
issn = {1532-3064},
abstract = {Mitochondria are increasingly recognized as central arbiters of cellular fate, placing them at the nexus of pulmonary health and disease. Beyond their canonical role in adenosine triphosphate (ATP) synthesis, these organelles are critical hubs for redox signaling, metabolic homeostasis, and programmed cell death. Mitochondrial dysfunction-a multifaceted condition characterized by impaired bioenergetics, excessive reactive oxygen species (ROS) production, aberrant dynamics, and defective quality control via mitophagy-is a unifying pathogenic feature in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH). This dysfunction is also a critical determinant of severity in acute conditions like acute lung injury (ALI) and COVID-19 and is a key mechanistic driver of Long COVID. This review synthesizes the core mechanisms of mitochondrial impairment, delineates their specific contributions to this spectrum of pulmonary pathologies, and discusses the burgeoning field of mitochondria-targeted therapeutics. Strategies ranging from targeted antioxidants and metabolic modulators to novel regenerative approaches like mitochondrial transplantation are highlighted, with an expanded discussion on their limitations, challenges, and clinical implications. By framing mitochondrial integrity as a critical determinant of pulmonary disease, we underscore a pivotal axis for future diagnostic and therapeutic innovation.},
}

@article {pmid41239971,
year = {2025},
author = {Sun, H and Mullington, JM and Thomas, RJ},
title = {Post-Infection Sleep Syndrome: Long COVID as an Example.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf366},
pmid = {41239971},
issn = {1550-9109},
}

@article {pmid41239762,
year = {2025},
author = {Covre, ER and Laranjeira, C and Carreira, L and Höring, CF and Góes, HLF and Baldissera, VDA and Marques, PG and Meireles, VC and Tostes, MFDP and Oliveira, RR and Paiano, M and Ageno, RS and Moroskoski, M and Alcaraz, JP and Vissoci, JN and Facchini, LA and Salci, MA},
title = {Prevalence and Predictors of Long Covid in a Cohort of Brazilian Adults 12 Months After Acute Infection: A Cross-Sectional Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70467},
pmid = {41239762},
issn = {1369-7625},
support = {//This study was funded by Ministério da Ciência, Tecnologia, Inovações e Comunicações (FNDCT/MCTIC), Ministério da Saúde (MS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-Processo n◦ 402882/2020-2. It was also supported by FCT-Fundação para a Ciência e a Tecnologia, I.P. (UID/05704/2023) and by the Scientific Employment Stimulus-Institutional Call-[https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 20 September 2025]./ ; },
mesh = {Humans ; Brazil/epidemiology ; Cross-Sectional Studies ; Female ; *COVID-19/epidemiology ; Middle Aged ; Male ; Prevalence ; Adult ; Aged ; SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Young Adult ; Severity of Illness Index ; },
abstract = {INTRODUCTION: Since the onset of the pandemic in early 2020, various reports have emerged regarding persistent symptoms associated with Covid-19. Nevertheless, there is insufficient data on the persistence of symptoms over time. This study sought to estimate the prevalence of persistent symptoms 12 months after Covid-19 infection and identify predictors of long Covid in adults living in the State of Paraná, southern Brazil, according to the level of severity of Covid-19 infection.

METHOD: An observational and cross-sectional survey was conducted with Brazilian adults diagnosed with Covid-19, as assessed from data available in two official Covid-19 notification databases in Brazil, using telephone interviews. Descriptive statistics, tests of associations and simple and multiple binary logistic regression analysis were used to identify predictors of long Covid.

RESULTS: In total, 1033 adults participated in the study. The overall prevalence of long Covid was 60.3% (n = 623). Prevalence was higher in women (67.7%), people aged between 50 and 59 years (65.8%) and in individuals who received treatment in an Intensive Care Unit (ICU) during the acute phase of Covid-19 infection (74.4%, n = 241). The risk factors associated with a greater chance of developing long Covid were: female (OR 2.38; 95% CI 1.55; 3.66), living in the Brazilian northwest health macro-region (OR 2.20; 95% CI 1.21; 4.00), presenting multimorbidity (OR 1.86; 95% CI 1.06; 3.28), having an average of six symptoms in the acute phase of Covid-19 (OR 1.22; 95% CI 1.17; 1.28) and having received treatment in an ICU (OR 4.86; 95% CI 2.83; 8.35) and inpatient ward (OR 2.45; 95% CI 1.47; 4.09).

CONCLUSIONS: The results highlight the high prevalence of long Covid and support the formulation of health policies capable of minimising the consequences on the population, on the services offered by professionals and on health systems.

The study topic's importance was based on the patients' experiences in the author's previous research and the need to develop patient-centred care.},
}

Humans
Brazil/epidemiology
Cross-Sectional Studies
Female
*COVID-19/epidemiology
Middle Aged
Male
Prevalence
Adult
Aged
SARS-CoV-2
Risk Factors
Post-Acute COVID-19 Syndrome
Young Adult
Severity of Illness Index

@article {pmid41239370,
year = {2025},
author = {Lindblom, S and Lindberg, P and Ljunggren, G and Lee, S and Kisiel, MA and Kolosenko, I and Petrovic, P and Sklivanioti Greenfield, M and Wachtler, C and Fedorowski, A and Wheelock, ÅM and Carlsson, AC},
title = {Prevalence of depression, anxiety, fatigue, and headache before and after long COVID onset: a case-control study in the total population of Region Stockholm.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {633},
pmid = {41239370},
issn = {1741-7015},
support = {M23-01339//Åke Wiberg Stiftelsen/ ; HLF20210053//The Swedish Heart-lung foundation/ ; 2021-06546//The Swedish Research Council/ ; FoUI-97300//Region Stockholm/ ; },
mesh = {Humans ; Male ; Female ; Sweden/epidemiology ; *COVID-19/epidemiology/psychology/complications ; *Fatigue/epidemiology/etiology ; *Headache/epidemiology/etiology ; Case-Control Studies ; Middle Aged ; *Anxiety/epidemiology ; *Depression/epidemiology ; Prevalence ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection, or long COVID, include diverse symptoms and remain a major concern worldwide. This study investigates the occurrence of depression, anxiety, fatigue, and headache 1 year prior to the COVID-19 pandemic (2019), 12 months prior to, and 6 months after long COVID diagnosis in individuals diagnosed with long COVID and matched population-based controls.

METHODS: This case-control study included nonhospitalized individuals diagnosed with long COVID compared with controls without long COVID, matched by age, sex, and neighborhood socioeconomic status. Data were collected from the Stockholm Regional Health Care Data Warehouse (VAL), including diagnoses in 2019, 12 months before, and 6 months after the long COVID diagnosis. Conditional logistic regression was used to calculate odds (OR) ratios and 99% confidence intervals (CI).

RESULTS: A total of 5589 cases (mean age: 47 years, 69% female) and 47,561 controls were included. Individuals with long COVID had a higher pre-pandemic frequency of the following diagnoses: depression (women: OR 1.57 (1.26-1.97), men: OR 1.40 (0.88-2.23)), anxiety (women: OR 1.65 (1.41-1.93), men: OR 2.10 (1.56-2.84)), fatigue syndrome after viral infection (women: OR 1.96 (0.86-4.48), men: OR 2.22 (0.29-17)), and headache (women: OR 2.45 (1.96-3.05), men: OR 2.89 (1.86-4.50)). Individuals with long COVID also had a higher frequency of these diagnoses 12 months before and 6 months after the long COVID diagnosis was made, regardless of sex.

CONCLUSIONS: Individuals with long COVID had a higher prevalence of depression, anxiety, fatigue, and headache both before and after being diagnosed with long COVID compared with controls without long COVID. The findings suggest an association between mental health vulnerabilities and long COVID, while the frequency of registered mental health diagnoses remained largely similar after the long COVID diagnosis.},
}

Humans
Male
Female
Sweden/epidemiology
*COVID-19/epidemiology/psychology/complications
*Fatigue/epidemiology/etiology
*Headache/epidemiology/etiology
Case-Control Studies
Middle Aged
*Anxiety/epidemiology
*Depression/epidemiology
Prevalence
Adult
Aged
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid41239121,
year = {2025},
author = {Villasis, NA and Santos, JJ and Ettner, SL and Xu, H and Escarce, JJ and Leung, LB},
title = {Long COVID Disproportionately Reported by Disadvantaged Individuals: A National Survey of U.S. Working-Age Adults.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-09912-w},
pmid = {41239121},
issn = {1525-1497},
support = {1RF1MH133436-01/MH/NIMH NIH HHS/United States ; IK2 HX002867/HX/HSRD VA/United States ; },
abstract = {BACKGROUND: COVID-19 disproportionately affects racial/ethnic minorities and economically disadvantaged persons, which may also apply to sequelae from acute infection. Little is known about those who live with post-acute sequelae of SARS-CoV-2 infection (PASC), including long COVID, especially those without a formal diagnosis.

OBJECTIVE: To examine self-reported long COVID symptoms and its associations with individual and state characteristics from a national survey sample of working-age adults.

DESIGN: Repeated cross-sectional survey analysis.

PARTICIPANTS: Eighteen- to 64-year-old adults who reported ever having had COVID-19 (n = 409,087).

MAIN MEASURES: We examined long COVID responses from the online Household Pulse Survey (9/22/2022-10/30/2023), administered by the Census Bureau and the National Center for Health Statistics. Long COVID was defined as having "symptoms lasting 3 months or longer that you did not have prior to having coronavirus" (e.g., fatigue, difficulty thinking, shortness of breath) or not. Logistic regression models adjusted for survey week, respondent characteristics (e.g., demographics, acute COVID-19 severity), and state characteristics (e.g., rurality, Health Professional Shortage Areas). We additionally examined concurrent depression and anxiety symptoms.

KEY RESULTS: The HPS response rate was 6.10% during the study timeframe.[14] Among those who ever had COVID-19, 27.5% reported long COVID symptoms. Among those with long COVID symptoms, 22.6% reported having severe activity limitations. In fully adjusted models, long COVID symptoms were most commonly reported by Hispanic respondents (ΔPH = 2.3, SE = 0.7), among all racial-ethnic groups. Low socioeconomic status was consistently associated with long COVID symptoms: Income (ΔP<25k vs >=200k+ = 11.9, SE = 0.9); Medicaid-insurance (ΔPMedicaid v Employer-sponsored = 02.9, SE = 0.5); Uninsurance (ΔPUninsured v Employer-sponsored = 1.8, SE = 0.4). Long COVID symptoms were associated with living in more rural states (ΔP = 0.08, SE = 0.02). Long COVID symptoms were additionally associated with concurrent anxiety (ΔPAnx v Not = 8.0, SE = 0.4) and depressive symptoms (ΔPDep v Not = 6.7, SE = 0.6).

CONCLUSIONS: Long COVID symptoms and disability were disproportionately reported among survey respondents who were Hispanic and who were economically-disadvantaged. Rural communities were more so impacted.},
}

@article {pmid41238605,
year = {2025},
author = {Toyokura, E and Yamada, K and Asai, K and Tsutsumi, M and Ueda, T and Hirai, K and Furukawa, Y and Miyamoto, A and Nishimura, M and Sato, K and Watanabe, T and Tabuchi, T and Kawaguchi, T},
title = {Dual use of combustible and heated tobacco products associates persistent symptoms with a history of COVID-19: a JASTIS 2023 cross‑sectional study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {38659},
pmid = {41238605},
issn = {2045-2322},
support = {JP23K07631//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *COVID-19/epidemiology ; Middle Aged ; Adult ; SARS-CoV-2 ; *Tobacco Products/adverse effects ; Aged ; Risk Factors ; Dyspnea/etiology/epidemiology ; Cigarette Smoking/adverse effects ; },
abstract = {Multiple reports have identified smoking as a risk factor for long COVID; however, few have distinguished among tobacco product types. We conducted a cross-sectional study using data from an internet-based survey administered in February 2023 to examine the association between 12 persistent symptoms and smoking status in participants with a history of COVID-19. A total of 28,250 participants were included, of whom 5,068 had a history of COVID-19. Among current tobacco users with a history of COVID-19, the odds ratios for persistent symptoms were significantly elevated for four symptoms-arthralgia, chest pain, dyspnea, and dysosmia-compared to never smokers. For subgroup analysis, current tobacco users were categorized into three groups: combustible cigarette (CC), heated tobacco product (HTP), and dual users. Among dual users, the odds ratios were significantly elevated for five symptoms: arthralgia, chest pain, dyspnea, dysgeusia, and dysosmia. CC users showed significantly higher odds for chest pain, dyspnea, and fatigue, while HTP users for dyspnea and sexual dysfunction. Smoking in individuals with a history of COVID-19 associates the prevalence of persistent symptoms, and its impact may vary by smoking type. Separately analyzing smoking subgroups allows for a more accurate understanding of the relationship between persistent symptoms and smoking behavior.},
}

Humans
Male
Cross-Sectional Studies
Female
*COVID-19/epidemiology
Middle Aged
Adult
SARS-CoV-2
*Tobacco Products/adverse effects
Aged
Risk Factors
Dyspnea/etiology/epidemiology
Cigarette Smoking/adverse effects

@article {pmid41238390,
year = {2025},
author = {Waters, A},
title = {Long covid: Government failure to recognise disease as occupational is "unconscionable," say unions.},
journal = {BMJ (Clinical research ed.)},
volume = {391},
number = {},
pages = {r2407},
doi = {10.1136/bmj.r2407},
pmid = {41238390},
issn = {1756-1833},
}

@article {pmid41238086,
year = {2025},
author = {Yuan, RL and Wang, SS and Li, PY and Ruan, Y and He, JQ and Zhou, R and Wang, WF and Jiang, YT and Ye, JR and Peng, Y and He, WB and Chu, SF and Zhang, Z and Chen, NH},
title = {SARS-CoV-2 spike protein induces depressive-like behaviors by disrupting astrocytic Cx43-mediated gap junction intercellular communication.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106176},
doi = {10.1016/j.bbi.2025.106176},
pmid = {41238086},
issn = {1090-2139},
abstract = {BACKGROUND: Long COVID has emerged as a global health concern, with depression being one of its most debilitating and poorly understood manifestations. Despite evidence pointing to the role of neuroinflammation and astrocyte-mediated disruptions in brain function, the mechanistic details remain elusive.

METHODS: SARS-CoV-2 spike receptor-binding domain (RBD) was microinjected into the medial prefrontal cortex (mPFC) to mimic cerebral infection, and the depressive-like behaviors, functional connectivity, and neuronal excitability were recorded for a 16-day period. Immunofluorescence, RNA sequencing, and ELISA were used to evaluate astrocytic gap junctions and inflammation. Gap junction intercellular communication (GJIC) dysfunction was confirmed by transfer of lucifer yellow (LY), cyclic adenosine monophosphate (cAMP), and cyclic GMP-AMP (cGAMP). We also investigated the role of Cx43 using conditional knockout mice, Gap 27-treated mice, and Cx43-knockdown astrocytes. Astrocytic Cx43 overexpression and celecoxib treatment were tested as a potential therapeutic to rescue Cx43 function.

RESULTS: Mice microinjected with RBD into the mPFC exhibited significant depressive-like behaviors, decreased neuronal excitability, and disrupted functional connectivity, accompanied by a marked reduction in astrocytic Cx43 expression and impaired GJIC. Functional assays, including Lucifer Yellow, cAMP, and cGAMP transfer, confirmed compromised gap junction activity, which was further associated with enhanced astrocytic type I interferon responses and cGAS-STING pathway activation. Conditional knockout of Cx43 in astrocytes or pharmacological inhibition of GJIC mimicked the depressive-like phenotypes induced by RBD. Importantly, Astrocytic Cx43 overexpression and celecoxib treatment restored Cx43 expression, improved GJIC, and effectively alleviated depressive-like behaviors in RBD-injected mice.

CONCLUSIONS: Astrocytic Cx43-mediated GJIC as a promising therapeutic strategy for managing depression in long COVID.},
}

@article {pmid41237918,
year = {2025},
author = {Aggarwal, A and Chanda, A},
title = {Effects of thoracic spinal manipulation in long COVID patients: A randomised controlled trial.},
journal = {Respiratory medicine},
volume = {250},
number = {},
pages = {108503},
doi = {10.1016/j.rmed.2025.108503},
pmid = {41237918},
issn = {1532-3064},
abstract = {INTRODUCTION: Long COVID patients manifest dyspnoea, chest heaviness, and symptoms, ascertaining deteriorated lung function. As thoracic spinal manipulation in such patients may lead to spinal misalignment, the chest wall compliance may also get affected. This study aimed to determine the role of thoracic spinal manipulation on pulmonary function, thoracic spine mobility, and chest expansion in patients with Long COVID.

METHODS: A Randomised Controlled trial was done in Dr. D.Y. Patil College of Physiotherapy, Pune, Maharashtra on 42 individuals who fulfilled the inclusion criteria. They were randomly assigned to two groups using the chit method. The experimental group (Group A), with a mean age of 23.85 ± 3.55 years (11 males, 10 females), underwent thoracic spinal manipulation in conjunction with pulmonary rehabilitation five times a week for two weeks. The control group (Group B) with a mean age of 24.9 (±5.26) years (9 males, 12 females) underwent pulmonary rehabilitation only. After two weeks, primary outcome measures, including pulmonary function, thoracic spine mobility, and chest expansion, were evaluated. The data were analysed with SPSS version 21 software using the Wilcoxon signed-rank and Mann-Whitney tests for within- and between-groups comparisons.

RESULTS: The experimental group showed a significant improvement (p < 0.05) in pulmonary function and thoracic spine mobility, except for thoracolumbar extension and chest expansion parameters versus control group. Within-group analysis of both groups, yielded significant results for all dependent outcome variables. (p < 0.05).

CONCLUSION: The study supports the role of thoracic spinal manipulation in improving pulmonary function and thoracic spine mobility in patients with Long COVID.},
}

@article {pmid41237491,
year = {2025},
author = {Staggs, H and Furst, A and Mills-Finnerty, C},
title = {Characterizing predictors and chronicity of brain fog in long COVID.},
journal = {Psychiatry research},
volume = {354},
number = {},
pages = {116813},
doi = {10.1016/j.psychres.2025.116813},
pmid = {41237491},
issn = {1872-7123},
abstract = {Long COVID is a chronic illness that persists following COVID-19 infection, with fatigue and brain fog as the most frequent complaints. However, there is no objective case definition for brain fog in long COVID and chronicity of symptoms remains unclear. This study recruited two waves of participants: those with a history of COVID-19, who participated in 2023 (N = 793, age = 38.5 ± 13.2, 44% female, 35.1% long COVID) and a follow up cohort collected in 2024 of participants who qualified as having long COVID at time point 1 (N=119, 61 female, 58 male). Participants completed questionnaires and cognitive tasks from home. We trained a binary classification model for long COVID diagnosis (73% accuracy) and a linear regression model for cognitive complaints (RMS error 5.8). A long COVID diagnosis at timepoint 1 was classified by biopsychosocial variables including stress, social support, and sex (women more likely). Symptom clustering revealed that phenotypes with both mental and physical health symptoms were predictive of brain fog, but not phenotypes with only sleep-related or physical symptoms. Markers of brain fog included slower reading and typing, slower reaction times in cognitive tasks, and changes in information processing speed and thresholds for making choices. Timepoint 2 data showed that the majority (82.4%) of participants did not remit from long COVID . These findings highlight the complex biopsychosocial factors that predict having long COVID with brain fog, and the need for interventions to improve remission rates.},
}

@article {pmid41237093,
year = {2025},
author = {, },
title = {Correction: Coping with stressful life disruptions due to long COVID: A qualitative study.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0336986},
pmid = {41237093},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0329831.].},
}

@article {pmid41235245,
year = {2025},
author = {Chen-Camaño, R and DeAntonio, R and López-Vergès, S},
title = {T-cell exhaustion in COVID-19: what do we know?.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1678149},
pmid = {41235245},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *T-Lymphocytes/immunology ; T-Cell Exhaustion ; },
abstract = {T-cell exhaustion is a terminal state of immune dysfunction characterized by impaired proliferation and effector functions, diminished cytokine secretion, and sustained expression of inhibitory receptors. In coronavirus disease 2019 (COVID-19), increasing evidence links exhausted T-cell phenotypes with poor clinical outcomes, including severe disease, delayed viral clearance, and persistent symptoms associated with Long COVID. Exhaustion results from prolonged antigenic stimulation and inflammatory signals and is marked by transcriptional reprogramming, metabolic and epigenetic dysregulation, and co-expression of inhibitory receptors such as programmed cell death protein-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Notably, exhausted phenotypes in COVID-19 frequently coexist with hyperactivation, raising the unresolved question of whether inhibitory receptor expression reflects transient activation or irreversible dysfunction. Emerging therapeutic strategies to reverse these dysfunctional states include immune checkpoint inhibitors, cytokine modulation, metabolic interventions, and epigenetic therapies, although their clinical translation remains at an early stage. Critical research gaps include the scarcity of longitudinal data, incomplete profiling of T-cell subsets across disease stages during COVID-19 and Long COVID-19, and contradictory evidence of vaccine-induced exhaustion with limited understanding of its consequences. This non-systematic literature review synthesizes current advances in COVID-19 immunopathology and therapeutic strategies, underscoring that understanding T-cell exhaustion is crucial to improving outcomes and shaping next-generation immunotherapies and vaccines.},
}

Humans
*COVID-19/immunology
*SARS-CoV-2/immunology
*T-Lymphocytes/immunology
T-Cell Exhaustion

@article {pmid41235244,
year = {2025},
author = {Wang, D and Zhang, F},
title = {CKD-related impairment in humoral and cellular immune response and potential correlation with long COVID-19: a systematic review.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1690298},
pmid = {41235244},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention & control ; *Immunity, Humoral ; *Renal Insufficiency, Chronic/immunology/therapy ; *Immunity, Cellular ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/blood/immunology ; Vaccination ; },
abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of morbidity and mortality from SARS-CoV-2 infection (COVID-19). However, their immune response to vaccination may vary among individuals. The purpose of this review was to identify characteristics of alterations in humoral and cellular immune responses to the vaccination, and to provide insights into their immune dysfunctions for a better care of acute COVID-19 and prevention of long COVID-19.

METHODS: PubMed, Embase, Scopus, Web of science and Cochrane Central were systematically searched. Eligible publications included clinical studies reporting immune response to COVID-19 vaccination in CKD patients without dialysis or KT, CKD patients undergoing dialysis, as well as CKD patients with KT. Demographics, measurements and results of their humoral and cellular response were evaluated, and the quality of studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tool and the Newcastle-Ottawa quality assessment scale (NOS).

RESULTS: A total of 31 eligible studies were identified. A decreased proportion of patients with KT showed anti-S IgG positivity after the 2[nd] (67%) and 3[rd] (56.6%) dose of vaccination. Similarly, a decreased proportion of these patients presented S-specific T-cell response after the 2[nd] (17.7%) and 3[rd] (12.9%) dose. Though lower anti-S IgG titers in patients with CKD or on dialysis, as well as T-cell response in patients on dialysis were reported to be lower after the 2[nd] or 3[rd] dose of vaccination, conflicting results were reported by other studies. Limited studies on correlated change between humoral and cellular immune response revealed a low rate of co-presence of the two in patients with dialysis, though antibody level was correlated with rate of cellular response, while no such correlation was revealed in patients with KT.

CONCLUSION: The study provides crucial information on features of humoral and cellular immune responses to COVID-19 vaccinations in CKD patients, and suggests possible directions for strategy of management such as antibody monitoring, additional booster dose or immunomodulatory therapies not only for acute COVID-19 but also for long COVID-19.},
}

Humans
*COVID-19/immunology/prevention & control
*Immunity, Humoral
*Renal Insufficiency, Chronic/immunology/therapy
*Immunity, Cellular
*SARS-CoV-2/immunology
*COVID-19 Vaccines/immunology
Antibodies, Viral/blood/immunology
Vaccination

@article {pmid41232803,
year = {2025},
author = {Brand, O and Kirkham, S and Jagger, C and Ozols, M and Purohit, K and Zhang, Z and Lennon, R and Hussell, T and Eckersley, A},
title = {Lung basement membranes are compositionally and structurally altered following resolution of influenza infection.},
journal = {Mucosal immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mucimm.2025.11.005},
pmid = {41232803},
issn = {1935-3456},
abstract = {Identification of pathways preventing timely recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected, reduction in lung basement membrane proteins 21 days after influenza infection when mice had symptomatically recovered. Basement membrane provides a critical scaffold for heterogeneous cell types and the proteins they secrete/express at the endothelial and epithelial barrier. Further peptide location fingerprinting analysis shows inherent structure-associated changes within core collagen IV and laminin components, particularly within the NC1 domains of collagen IV. Our results imply lingering damage to the basement membrane network despite symptomatic recovery from viral infection. Surprisingly, similar structure-associated changes in laminin and collagen IV components are also observed in non-infected, aged mice indicating that inflammation-driven basement membrane degeneration may contribute to tissue ageing. Interestingly, macrophages in regions deficient in basement membrane express collagen IV and laminin chains. Repair of the basement membrane should therefore be targeted to improve overall lung health. Non-technical summary: Lung virus infection is a constant global threat, despite developments in vaccination and anti-viral treatments. We have a deep understanding of this inflammatory condition but less is known about the drivers of persistent problems, including fatigue and breathlessness as illustrated by "long COVID". Here, we reveal a novel finding that a critical structure in the lung (the basement membrane) remains damaged after the influenza virus and symptoms have cleared. This structure supports a variety of cells and forms a barrier that lines the airspaces. It also regulates fluid and cell movement into these airspaces. Remarkably, we show that similar changes after virus infection are also evident in aged lungs, which implies that lung complications with age may be due to repeated inflammation. By identifying these persistent basement membrane changes, we provide an entirely novel area to target with new medicines to treat complications arising from viral infection.},
}

@article {pmid41232748,
year = {2025},
author = {Silva, CAC and Bomfim, AP and Medeiros, JD and Silva, JJ and Cazé-Ceron, AB and Cerqueira-Silva, T and Khouri, R and Barral, A and Barral-Netto, M and Fernandes, GDR and Barbosa, CG and Boaventura, VS},
title = {Nasal Microbiota and Clinical Features in Acute Flu-Like Illness: COVID-19 Status and Long COVID Follow-Up.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108196},
doi = {10.1016/j.ijid.2025.108196},
pmid = {41232748},
issn = {1878-3511},
abstract = {OBJECTIVES: Long COVID (LC) is a challenging medical condition. Reliable diagnostic and targetable biomarkers of LC for a proper and early diagnosis and clinical care are an unmet medical need. Evaluate targetable biomarkers for LC management.

DESIGN: Comparison of nasal microbiota and clinical features in 291 individuals with acute influenzae-like illness (ILI), comparing COVID-19-positive (n=193) and negative (n=98) groups, with further stratification by long COVID (LC) outcomes (persistent symptoms >3 months).

RESULTS: Clinical characteristics were balanced across groups, with upper respiratory symptoms predominating. Individuals who developed LC exhibited more cardiorespiratory symptoms during acute infection (70% versus 48%, p=0.002). Nasal microbiota analysis revealed lower alpha diversity in COVID-19-positive individuals versus other ILI (Wilcoxon: Chao2 p=0.03305; Shannon p=0.02578; Simpson p=0.1082) but no differences in beta diversity or taxonomic composition between groups, including LC versus recovered individuals. EBV/CMV infection/reactivation was not associated with LC. Sensitivity analyses confirmed robustness to methodological and temporal biases.

CONCLUSIONS: Findings suggest acute nasal microbiota disruption in individuals with COVID-19, but no LC-specific microbial profile.},
}

@article {pmid41232201,
year = {2025},
author = {Nunes, M and Kruger, A and Fielding, B and Kell, DB and Pretorius, E},
title = {The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters.},
journal = {Thrombosis research},
volume = {256},
number = {},
pages = {109530},
doi = {10.1016/j.thromres.2025.109530},
pmid = {41232201},
issn = {1879-2472},
abstract = {Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor-depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.},
}

@article {pmid41231196,
year = {2025},
author = {O'Connor, DB and Greenwood, DC and Mansoubi, M and Bakerly, ND and Bhatia, A and Collett, J and Davies, HE and Dawes, J and Delaney, BC and Ezekiel, L and Leveridge, P and Mir, G and Muehlhausen, W and Rayner, C and Scott, JT and Sivan, M and Tucker-Bell, I and Vashisht, H and Ward, T and Winch, D and Dawes, H and , },
title = {Daily stress and worry are additional triggers of symptom fluctuations in individuals living with Long COVID: results from an intensive longitudinal cohort study.},
journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine},
volume = {59},
number = {1},
pages = {},
pmid = {41231196},
issn = {1532-4796},
support = {//National Institute for Health and Care Research/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/psychology/complications/physiopathology ; *Stress, Psychological/psychology/complications ; Middle Aged ; Longitudinal Studies ; *Anxiety/psychology ; Aged ; Fatigue/psychology ; Adult ; *Depression/psychology ; *Rumination, Cognitive/physiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; United Kingdom ; Dizziness ; SARS-CoV-2 ; *Symptom Flare Up ; },
abstract = {BACKGROUND: Recent research has shown that exertion in physical, cognitive, social, and self-care activities triggers symptom severity in individuals with Long COVID.

PURPOSE: The current study aimed to investigate whether daily emotional exertions (stress, worry, rumination) were associated with symptom exacerbation, over and above influences of effortful daily activities, in individuals with Long COVID.

METHODS: In total, 376 participants were recruited from UK Long COVID clinics and community settings and completed daily assessments of activity and severity of 8 core symptoms every 3 hours for up to 24 days; 155 participants completed daily assessments of stress, worry, and rumination for at least 7 consecutive days.

RESULTS: Days with higher stress scores were associated with increased severity of all symptoms on the same day, after adjusting for activities, demographic and medical factors (P-values ≤ .007). Days with higher stress scores also predicted more severe anxiety and depression symptoms 1 day later (P < .001) and more severe anxiety (P < .001) and dizziness symptoms (P = .003) 2 days later. Days with higher worry scores were associated with increased fatigue (P < .001), anxiety (P < .001), depression (P < .001), and cognitive dysfunction (P = .002) on the same day, but decreased anxiety (P = .003) and depression (P = .002) symptoms 1 day later and less severe pain (P = .002) symptoms 2 days later. Daily rumination was only associated with 2 symptoms.

CONCLUSIONS: Daily stress and worry are distinct factors linked to fluctuations in same-day and next-day Long COVID symptoms, with daily stress showing the strongest association-consistent with patterns of postexertional symptom exacerbation. These findings highlight the importance of considering stress and worry as potential therapeutic targets and integrating their management into self-care programs.},
}

Humans
Male
Female
*COVID-19/psychology/complications/physiopathology
*Stress, Psychological/psychology/complications
Middle Aged
Longitudinal Studies
*Anxiety/psychology
Aged
Fatigue/psychology
Adult
*Depression/psychology
*Rumination, Cognitive/physiology
Severity of Illness Index
Post-Acute COVID-19 Syndrome
United Kingdom
Dizziness
SARS-CoV-2
*Symptom Flare Up

@article {pmid41231115,
year = {2025},
author = {Rai, KK and Gowman, H and Harrison, CS and Gruben, DC and Butfield, R and Hulme, R and Volkman, HR and Nguyen, JL and Yang, J},
title = {Understanding the role of COVID-19 vaccination in all-cause healthcare resource utilisation among adults with long covid in the Uk primary care setting: data from the 2022-2023 respiratory virus season.},
journal = {Expert review of vaccines},
volume = {},
number = {},
pages = {},
doi = {10.1080/14760584.2025.2589215},
pmid = {41231115},
issn = {1744-8395},
abstract = {BACKGROUND: The role COVID-19 vaccination on healthcare resource utilization (HCRU) and cost remains unclear, especially during Omicron predominance and among high risk UK populations.

RESEARCH DESIGN AND METHODS: A retrospective cohort study using UK The Health Improvement Network (THIN) primary care data included adults (≥18 years) with confirmed or suspected COVID-19 between September 2022- May 2023. Three cohorts were defined: Highest risk (eligible for two seasonal doses), High Risk (eligible for one dose), and All COVID-19 patients. Long COVID was identified as ≥ 1 symptom or diagnostic/referral code, ≥4 weeks post COVID-19 diagnosis. Inverse probability of treatment weighting assessed associations between vaccination status (yes/no and time since vaccination) and long COVID, HCRU, and costs.

RESULTS: In both Risk Cohorts, COVID-19 vaccination was not associated with long COVID incidence. However, in the High Risk (n = 1,889) and All Patients cohorts (n = 8,507) outpatient specialist referrals were significantly lower in the 3-6-month post-vaccination group versus > 6 months (rate ratio: 0.28; 95% CI: 0.10-0.79, p < 0.05 and 0.46; 95% CI: 0.27-0.79; p ≤ 0.01, respectively).

CONCLUSIONS: COVID-19 vaccination was not consistently associated with incidence of long COVID or all-cause HCRU. Findings suggest potential subgroup-specific benefits, highlighting the importance of annual vaccination. Further research with larger sample size and longer-term follow-up is warranted.},
}

@article {pmid41230640,
year = {2025},
author = {Sargeant, S and Wilkinson, S and Lorraway, M and McDonald, S},
title = {Contested illness and communication: Positioning long Covid in online discussion forums.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053251389517},
doi = {10.1177/13591053251389517},
pmid = {41230640},
issn = {1461-7277},
abstract = {The World Health Organization (WHO) officially acknowledged long COVID as a post COVID-19 condition in 2021. Emerging research shows that long COVID may be considered a contested illness due to unknown causal mechanisms, diagnostic uncertainty, poor recovery/treatment outcomes and people reporting illness dismissal experiences when seeking healthcare. Informed by the sick role and positioning theories, this study explored people's experiences of seeking healthcare for long COVID by examining posts in two online forums (Mayo Clinic Connect and Reddit, from June and July 2023). Template analysis helped to identify12 forum threads containing a total of 305 posts. Inductive thematic analysis of posts identified three themes: (a) 'The concept of time', (b) 'The importance of symptom legitimacy', and (c) 'Responding to diagnostic dismissal'. Healthcare professionals are critical in validating the patient experience without a formal long COVID diagnosis, and in supporting long COVID recovery needs by acknowledging heterogeneity and diagnostic difficulties.},
}

@article {pmid41228073,
year = {2025},
author = {Cianciulli, A and Santoro, E and Manente, R and Pacifico, A and Barberio, I and Satriani, V and Boccia, G},
title = {Clinical and Symptom Profiles of Long-COVID Patients in Italy: A Cross-Sectional Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {41228073},
issn = {2227-9032},
abstract = {Background/Objectives: Long COVID is a multisystemic condition persisting beyond the acute phase of SARS-CoV-2 infection. Data on young, community-dwelling adults in Italy remain limited. To describe the sociodemographic, clinical, and symptom profiles of Long-COVID patients in an Italian cohort. Methods: Cross-sectional survey (February-April 2025) on 250 adults with prior COVID-19. A validated 24-item questionnaire was administered. Descriptive statistics, 95% confidence intervals (CIs), Hedges' g effect sizes, and exploratory subgroup analyses (sex, age ≤ 30 vs. >30) were performed. Results: Participants were 63.6% female, 56% ≤ 30 years, 4.4% with comorbidities. Acute symptoms included muscle/joint pain (2.79 ± 1.31), weakness (2.77 ± 1.28), and tiredness (2.76 ± 1.31). Persistent symptoms were excessive tiredness (2.36 ± 1.27), weakness (2.25 ± 1.29), and muscle/joint pain (2.25 ± 1.25). Acute → persistent changes were significant (p < 0.01, paired t-test) with effect sizes g = 0.31-0.42. Women reported higher persistent fatigue (mean diff = 0.40, 95% CI 0.01-0.78, p = 0.04). Conclusions: Even among young adults without comorbidities, Long COVID imposes a relevant burden. Findings highlight the need for multidisciplinary pathways, nursing-led follow-up, and targeted self-management education.},
}

@article {pmid41228071,
year = {2025},
author = {Neba, R and Pedaprolu, LS and Neba, B and Sambamoorthi, U},
title = {Long COVID Is Associated with Excess Direct Healthcare Expenditures Among Adults in the United States.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {41228071},
issn = {2227-9032},
abstract = {Background: Long COVID can lead to a considerable economic burden because of ongoing care for persistent symptoms such as fatigue, dyspnea, or cognitive dysfunction. However, systematic research quantifying healthcare expenditures associated with long COVID remains limited. Objective: This study estimated the excess total, payer, and out-of-pocket healthcare expenditures associated with long COVID among adults in the United States (US). Methods: This was a cross-sectional analysis on adults ≥18 years using 2022 Medical Expenditure Panel Survey (MEPS) data (N = 17,119; representing approximately 254 million adults). Economic burden was measured with (1) total, (2) payer, and (3) out-of-pocket expenditures by individuals and their families. Generalized linear models (GLMs) with gamma distribution and log link were utilized to estimate excess expenditures associated with long COVID after adjusting for age, sex, race and ethnicity, social determinants of health, health status, and lifestyle factors. Results: Overall, 7.0% of the population reported long COVID. Adults with long COVID exhibited higher total (USD 11,305 vs. USD 7162) and payer (USD 9983 vs. USD 6097) expenditures compared to those with no COVID. In a fully adjusted analysis, long COVID was associated with an excess of USD 4098 in total healthcare expenditures and USD 3705 in payer expenditures. We did not observe significant differences in out-of-pocket expenditures between those with long COVID and no COVID. Conclusions: Adults with long COVID had 1.5 times higher total healthcare costs compared to those without COVID. This study highlights the need for comprehensive strategies and policies to reduce the economic burden associated with long COVID.},
}

@article {pmid41227273,
year = {2025},
author = {Emmanouil, M and Georgakopoulou, VE and Drougkas, K and Lembessis, P and Skarlis, C and Gkoufa, A and Sipsas, NV and Mavragani, CP},
title = {Type I Interferon-Related Gene Expression and Laboratory Abnormalities in Acute Infection Are Associated with Long COVID Symptom Burden.},
journal = {Journal of clinical medicine},
volume = {14},
number = {21},
pages = {},
pmid = {41227273},
issn = {2077-0383},
abstract = {Background: Long COVID-defined as the persistence of symptoms or the development of new symptoms beyond four weeks after acute SARS-CoV-2 infection-affects an estimated 10-30% of individuals recovering from COVID-19, posing a significant public health burden. Emerging evidence suggests that type I interferons (IFNs) (a critical group of cytokines in the antiviral defense) and hematologic alterations, such as lymphopenia and elevated inflammatory markers, are linked to both the severity of acute COVID-19 and the likelihood of developing long-term symptoms. The aim of this study is to explore the association between type I IFN signatures and long COVID. A second aim is to examine the relationship between laboratory findings during acute infection and long COVID. Methods: The study included 61 patients investigated for the presence of long COVID symptoms 16.5 ±1.5 months after acute infection. Patients were divided into two groups of higher symptom burden of long COVID and those with milder symptoms based on demographic, laboratory, and clinical data as well as type I IFN-inducible gene expression (MX-1, IFIT-1, and IFI-44) measured in peripheral blood by real-time PCR. Data collected during acute infection were recorded. Peripheral blood samples were collected during the acute phase of infection, within the first 48 h of hospital admission. IFN-inducible gene expression was measured prospectively at that time, and RNA was extracted immediately for subsequent analysis. Results: History of intubation emerged as a significant associated factor of severe long COVID, with 75% of intubated patients reporting >8 persistent symptoms approximately 16 months post-infection. Higher white blood cell (WBC) and neutrophil counts but lower eosinophil and monocyte counts in acute infection were found to be associated with a high burden of long COVID symptoms. Interestingly, absolute monocyte count was found to independently correlate with higher long COVID symptom burden. Lactate dehydrogenase (LDH) and serum glutamic-oxaloacetic transaminase (SGOT) also differed significantly between groups, with higher levels correlating with a high burden of long COVID symptoms. Notably, MX-1 transcript levels in peripheral blood at the time of acute infection were reduced in patients with a high burden of long COVID symptoms, suggesting that dysregulated immune responses during the acute phase may contribute to persistent symptoms. Conclusions: These findings suggest the potential association of hematological and immune markers with long COVID severity, as well as the importance of monitoring these parameters to identify at-risk patients for early interventions.},
}

@article {pmid41227265,
year = {2025},
author = {Adeyemi, C and Breuer, L and Kodvawala, R and Miller, D and Powers-Fletcher, MV},
title = {A Cohort Study Characterizing the Outcomes Following an Acute SARS-CoV-2 Infection in Pregnancy.},
journal = {Journal of clinical medicine},
volume = {14},
number = {21},
pages = {},
pmid = {41227265},
issn = {2077-0383},
abstract = {Background/Objectives: Current estimates suggest that 6% of COVID-19 survivors develop a post-viral sequela known as Long COVID. Among those at risk for this sequela, pregnant individuals are a vulnerable patient population, but they are understudied as to the nature of their symptomology and potential adverse outcomes. Methods: This retrospective study evaluated a cohort of 150 pregnant individuals with a history of acute SARS-CoV-2 infection during pregnancy, observing for Long COVID symptoms and assessing for adverse outcomes. Of this cohort, 64% identified as Black and/or Latina, which provides a more diverse representation compared to previously published studies. Results: Within this cohort, 26.7% of individuals experienced at least one symptom of Long COVID; subcohorts, which were categorized based on presence or absence of Long COVID symptomology, presented with varying phenotypes. Pain, mental health dysfunction or psychological problems, and fatigue were the predominant symptoms documented for patients who averaged two Long COVID symptoms after at least 30 days following a COVID-19 diagnosis. Different adverse outcomes were higher in frequency among subcohorts, highlighting a need for continued study to explore the nuances of the impact of COVID-19 on this unique and vulnerable population. The most notable trends between subcohorts related to treatment patterns for acute COVID-19, vaccine status, and cesarean delivery rates. Conclusions: By providing a description of the documented health experience for a predominantly non-White cohort of individuals who were diagnosed with an acute SARS-CoV-2 during pregnancy, our study contributes to a foundation upon which future studies can build.},
}

@article {pmid41226731,
year = {2025},
author = {Varghese, S and Al-Hassani, I and Al-Aani, U and Rob, NJ and Al-Mannai, S and Jaguri, A and Yousif, RA and Al-Mulla, A and Palayangal, FF and Laws, S and Al-Ali, D and Zakaria, D},
title = {Long-Term Complications of Multisystem Inflammatory Syndrome in Children and Adults Post-COVID-19: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226731},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications ; *Systemic Inflammatory Response Syndrome/complications/therapy/etiology ; Child ; Adult ; SARS-CoV-2 ; },
abstract = {The SARS-CoV-2 pandemic has posed global medical challenges due to its ability to affect multiple organ systems. Among the post-COVID-19 complications, multisystem inflammatory syndrome has emerged as a severe condition affecting both children (MIS-C) and adults (MIS-A). This review aims to compile and analyze published data to investigate clinical characteristics, laboratory findings, and outcomes of MIS post-COVID-19. A comprehensive search of various databases was conducted to identify studies reporting MIS-related complications in pediatric and adult populations post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 64 studies met our inclusion criteria, and compiled results revealed that cardiac complications were the predominant manifestation followed by gastrointestinal, hematologic, neurological, and mucocutaneous involvement. Laboratory findings consistently demonstrated elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6. Most patients required hospitalization, and many needed intensive care; treatment typically involved IVIG, corticosteroids, and biologic therapies. While most patients recovered, a subset experienced persistent complications. These findings highlight the importance of early recognition, multidisciplinary management, and structured follow-up for MIS. Future research is warranted to clarify the underlying mechanisms, risk factors, and long-term outcomes associated with MIS in post-COVID-19 patients.},
}

Humans
*COVID-19/complications
*Systemic Inflammatory Response Syndrome/complications/therapy/etiology
Child
Adult
SARS-CoV-2

@article {pmid41226453,
year = {2025},
author = {Cimini, E and Vergori, A and Cimaglia, C and Tartaglia, E and Notari, S and Colavita, F and Matusali, G and Mastrorosa, I and Mazzotta, V and Chinello, P and Mencarini, P and Giancola, ML and Abdeddaim, A and Casetti, R and Grassi, G and Gili, S and Cristofanelli, F and Maggi, F and Piselli, P and Girardi, E and Antinori, A and Camici, M},
title = {Inflammatory Milieu and Specific T-Cell Response Observed Three Months and One Year After SARS-CoV-2 Infection in Long COVID Subjects.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226453},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/blood/pathology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Aged ; *T-Lymphocytes/immunology ; *Inflammation/immunology/blood ; Adult ; Intercellular Adhesion Molecule-1/blood ; Biomarkers/blood ; Cytokines/blood ; Interleukin-6/blood ; },
abstract = {Long COVID (LC) is characterized by a wide range of symptoms, the causes of which remain unclear. We investigated associations between inflammatory and coagulation factors, adaptive immune response to SARS-CoV-2, and LC. We enrolled 196 unvaccinated individuals with SARS-CoV-2 (March-June 2020). Blood samples were collected at three (T3M) and twelve (T12M) months post infection. Plasma concentrations of coagulation factors (D-Dimer, E-Selectin, ICAM-1, VCAM-1) and inflammatory markers (IL-6, IL-8, TNF-α, IL-1β) were measured by ELISA, and SARS-CoV-2-specific T-cell response was assessed by Elispot. LC occurred in 66/196 patients (34%); 77.8% had been hospitalized. Respiratory symptoms were present in 54%, fatigue in 30%, and neuropsychological symptoms in 14%. At T3M, hospitalized patients exhibited higher levels of ICAM-1, VCAM-1, and IL-6, along with increased immunoreactivity. LC patients exhibited elevated IL-8 and TNF-α and enhanced immunoreactivity at T3M, though these differences were not observed at T12M. Inflammatory and coagulation markers were altered at three months after acute infection, with some changes persisting at one year, suggesting a long-term immunological impact of SARS-CoV-2 on the inflammatory response. A SARS-CoV-2-specific T-cell response was still detectable at T12M, albeit at a lower level than at T3M, suggesting the persistence of protective memory T-cells beyond the acute phase.},
}

Humans
*COVID-19/immunology/blood/pathology
Male
Female
Middle Aged
*SARS-CoV-2/immunology
Aged
*T-Lymphocytes/immunology
*Inflammation/immunology/blood
Adult
Intercellular Adhesion Molecule-1/blood
Biomarkers/blood
Cytokines/blood
Interleukin-6/blood

@article {pmid41226417,
year = {2025},
author = {Charles, AL and Debrut, L and Oulehri, W and Vincent, V and Delagreverie, H and Asael, P and Riou, M and Giannini, M and Meyer, A and Geny, B},
title = {Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226417},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/mortality/metabolism/pathology ; *Leukocytes, Mononuclear/metabolism ; Female ; Male ; *Mitochondria/metabolism ; Middle Aged ; Severity of Illness Index ; Aged ; SARS-CoV-2 ; Oxygen Consumption ; Cell Respiration ; Adult ; },
abstract = {COVID-19 is a public health issue with a significant mortality rate and potential long-lasting disabling symptoms responsible for the long-COVID syndrome. Mitochondrial dysfunction is a key mechanism but whether peripheral blood mononuclear cell (PBMC) mitochondrial respiration changes might be associated with mortality and/or occurrence and severity of long-COVID syndrome remains to be investigated. We determined mitochondrial respiratory chain oxygen consumption in twenty COVID-19 patients hospitalized in the intensive care unit and analyzed their remaining symptoms at the third year after hospital release. PBMC mitochondrial respiration was decreased in COVID-19 patients compared to the control group (14.13 ± 2.35 vs. 6.21 ± 0.88 pmol/s/10[6] cell, p = 0.0006 for the OXPHOS state by CII). Considering COVID severity, such a decrease was greater in long-COVID patients and in patients who deceased (4.91 ± 0.75, p = 0.008 and 4.94 ± 1.11 pmol/s/10[6] cell, p = 0.04, respectively). PBMC markers of inflammation also increased with the severity of COVID (1.0 ± 0.08 vs. 14.45 ± 2.07, p = 0.02 for ISG15 in patients who died) and ISG15 negatively correlated with PBMC mitochondrial respiration (r = -0.67, p = 0.02 for CII). In conclusion, this study shows that the greater the impairment in PBMC mitochondrial respiration in patients hospitalized in the intensive care unit for COVID-19, the greater the mortality rate and the more severe the long-COVID symptoms-three years after hospital discharge. Further, PBMC markers of inflammation also increased with the severity of COVID and ISG15 negatively correlated with PBMC mitochondrial respiration. These results support that PBMC mitochondrial respiration might be a biomarker of COVID severity and further studies investigating whether modulation of PBMC mitochondrial respiration might improve COVID-19 patients' prognosis.},
}

Humans
*COVID-19/mortality/metabolism/pathology
*Leukocytes, Mononuclear/metabolism
Female
Male
*Mitochondria/metabolism
Middle Aged
Severity of Illness Index
Aged
SARS-CoV-2
Oxygen Consumption
Cell Respiration
Adult

@article {pmid41226415,
year = {2025},
author = {Zolotarenko, AD and Poghosyan, HM and Sheptiy, VV and Bruskin, SA},
title = {COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226415},
issn = {1422-0067},
support = {123120500032-9//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Humans ; *COVID-19/genetics/virology/immunology/pathology ; *SARS-CoV-2/physiology ; *Epigenesis, Genetic ; *Epigenome ; Biomarkers/metabolism ; Immunity, Innate ; *Host-Pathogen Interactions/genetics ; MicroRNAs/genetics ; DNA Methylation ; },
abstract = {The epigenetics of COVID-19 is a rapidly expanding field that reveals how the SARS-CoV-2 virus initiates alterations in the host's genome, influencing the susceptibility to infection, the disease severity, and long-term consequences, known as "long COVID." In this review, we describe the mechanisms utilized by the virus to manipulate the host epigenome, suppressing antiviral responses and creating a favorable environment for viral replication. We also highlight virus-induced epigenetic changes across diverse cell populations that contribute to COVID-19 pathogenesis. Notably, the virus reprograms hematopoietic stem and progenitor cells, leading to long-lasting alterations in innate immunity, a phenomenon known as "trained immunity." These epigenetic modifications are maintained in differentiated daughter cells and may explain the persistent inflammation and other symptoms of long COVID. Furthermore, we discuss emerging epigenetic biomarkers of disease severity, including methylation signatures in genes such as AIM2, HLA-C, and PARP9, as well as dysregulated miRNA profiles. Understanding this complex interplay between the virus and the host's epigenetic landscape is crucial for developing new therapeutic approaches that target specific epigenetic modifications to suppress pathological processes and improve clinical outcomes for COVID-19 patients.},
}

Humans
*COVID-19/genetics/virology/immunology/pathology
*SARS-CoV-2/physiology
*Epigenesis, Genetic
*Epigenome
Biomarkers/metabolism
Immunity, Innate
*Host-Pathogen Interactions/genetics
MicroRNAs/genetics
DNA Methylation

@article {pmid41225499,
year = {2025},
author = {Pokhilenko, I and Pallan, M and Murphy, M and Adab, P and Morrison, B and Sitch, A and Adamson, A and Bartington, S and Duff, R and Griffin, T and Hurley, K and Lancashire, E and McLeman, L and Passmore, S and Rowland, M and Ravaghi, V and Spence, S and Frew, E},
title = {Economic evaluation of the national school food standards across secondary schools in the Midlands, UK (the FUEL study): methodological challenges of undertaking health economics research within non-health settings.},
journal = {The international journal of behavioral nutrition and physical activity},
volume = {22},
number = {1},
pages = {142},
pmid = {41225499},
issn = {1479-5868},
support = {17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; 17/92/39//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *Schools/economics ; Cost-Benefit Analysis ; United Kingdom ; Quality of Life ; *Food Services/economics/standards ; Adolescent ; Child ; COVID-19 ; Female ; Male ; Oral Health ; Diet/economics ; },
abstract = {BACKGROUND: Economic evaluations of complex public health interventions are becoming increasingly important. This presents health economists with challenges of adapting methodologies originally designed for healthcare to other contexts, such as education. This study presents an economic evaluation of the UK School Food Standards (SFS), with a particular focus on the methodological challenges involved.

METHODS: The economic evaluation was conducted alongside an observational study comparing the SFS-mandated secondary schools to non-mandated schools in the Midlands (UK). Costs of food provision and SFS implementation were collected directly from schools and supplemented by secondary data on schools' catering expenditure. The outcomes included dietary intake, dental health, health-related quality of life (HRQoL), and educational performance, collected from pupils and secondary data. The analysis comprised a micro-costing, cost-consequence, and an exploratory cost-utility analysis, from school and societal perspectives.

RESULTS: Data were collected from 36 schools and 2,543 pupils. We found mandated schools spent less on food provision compared to non-mandated schools, and pupils attending mandated schools had marginally better HRQoL, dental health, and slightly worse nutritional intake. Mandated schools performed worse according to the educational outcomes. There were large amounts of missing cost data despite repeated data collection attempts, and the results of the cost-utility analysis were uncertain.

DISCUSSION: We found no clear evidence on the cost-effectiveness of the SFS in secondary schools, likely due to substantial variation in implementation and compliance across both mandated and non-mandated schools, as well as multiple challenges, including the COVID-19 pandemic, difficulties in collecting cost data from schools, and the complexity of the study context. This study highlights the challenges of primary cost data collection for evaluating complex interventions and the need to balance data accuracy with the resources required. As economic evaluations of school-based interventions become more common, there is a growing need to refine methods for such evaluations.},
}

Humans
*Schools/economics
Cost-Benefit Analysis
United Kingdom
Quality of Life
*Food Services/economics/standards
Adolescent
Child
COVID-19
Female
Male
Oral Health
Diet/economics

@article {pmid41223978,
year = {2025},
author = {Spanoghe, M and Antonacci, T and Schneider, N and Molmans, THJ},
title = {Viewpoint | linking long Covid and AD(H)D through neuroimmune dysfunction: A translational framework proposal for precision medicine.},
journal = {Brain, behavior, and immunity},
volume = {131},
number = {},
pages = {106181},
doi = {10.1016/j.bbi.2025.106181},
pmid = {41223978},
issn = {1090-2139},
}

@article {pmid41223398,
year = {2025},
author = {Canarslan-Demir, K and Ozgok-Kangal, K and Artan, E and Turgut, B},
title = {Does Covid-19 Cause Avascular Necrosis?.},
journal = {Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc},
volume = {52},
number = {3},
pages = {361-368},
pmid = {41223398},
issn = {1066-2936},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Retrospective Studies ; Male ; Female ; Middle Aged ; Risk Factors ; Adult ; *Femur Head Necrosis/etiology/epidemiology ; Hyperbaric Oxygenation ; Incidence ; *Osteonecrosis/etiology/epidemiology ; Aged ; },
abstract = {COVID-19 has been associated with an increased risk of avascular necrosis (AVN), which affects various joints, including the hip, vertebrae, knee, and jaw. Understanding AVN's pathogenesis and risk factors as a consequence of COVID-19 is essential for improving treatment and identifying preventive measures. This retrospective cohort study aims to assess the impact of COVID-19 on the etiology of AVN and raise awareness among clinicians. The study analyzed patients diagnosed with AVN and treated with Hyperbaric Oxygen Therapy at Gülhane Training and Research Hospital from January 2018 to January 2023. Patients were categorized into two groups: those admitted before the pandemic (the control group) and those admitted after (the study group). The results showed a significant increase in AVN cases during the post-pandemic period, with a higher incidence of femoral head involvement and more advanced stages of AVN in patients with a history of COVID-19. The findings suggest that COVID-19 and high-dose steroid use may increase AVN risk, highlighting the need for careful steroid management and monitoring for joint pain in these patients. Further research is recommended to explore the link between COVID-19 and AVN, the duration of symptoms, and the prognostic implications.},
}

Humans
*COVID-19/complications/epidemiology
Retrospective Studies
Male
Female
Middle Aged
Risk Factors
Adult
*Femur Head Necrosis/etiology/epidemiology
Hyperbaric Oxygenation
Incidence
*Osteonecrosis/etiology/epidemiology
Aged

@article {pmid41223394,
year = {2025},
author = {Zamora, FV and Santos, ACFF and Zamora, AV and Galvao, LKCS and Pimenta, NDS and Salles, JPCEA and Carneiro, VB and Starling, CEF},
title = {Hyperbaric Oxygen Treatment for Long-COVID syndrome: A Systematic Review of Current Evidence on Cognitive Decline.},
journal = {Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc},
volume = {52},
number = {3},
pages = {327-335},
pmid = {41223394},
issn = {1066-2936},
mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *Cognitive Dysfunction/therapy/etiology ; *COVID-19/complications ; Executive Function ; Post-Acute COVID-19 Syndrome ; Attention ; Randomized Controlled Trials as Topic ; Fatigue/therapy ; },
abstract = {INTRODUCTION: There is no established specific treatment for long-COVID syndrome (LCS), yet hyperbaric oxygen (HBO2) treatment has been studied as a potential option. Therefore, we conducted a systematic review to evaluate the benefits of HBO2 treatment in LCS patients.

METHODS: We systematically searched PubMed, Embase, and Cochrane databases until April 2024. Risk of bias and GRADE quality assessment were evaluated. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42024530421.

RESULTS: Seven studies from seven countries, divided into RCTs and observational studies, included 199 participants. HBO₂ treatment protocols included breathing 100% oxygen at 2.0 ATA until 2.5 ATA; the number of sessions varied from ten to 60 depending on the patient's comorbidities and symptoms. Memory, executive function, attention, fatigue, and pain level improved with HBO2 treatment. The intervention had minimal side effects, and none were serious.

CONCLUSION: HBO₂ treatment might be a potential option and safe treatment in LCS patients. However, further research should be focused on evaluating its efficacy in a larger number of patients through randomized studies.},
}

Humans
*Hyperbaric Oxygenation/methods
*Cognitive Dysfunction/therapy/etiology
*COVID-19/complications
Executive Function
Post-Acute COVID-19 Syndrome
Attention
Randomized Controlled Trials as Topic
Fatigue/therapy

@article {pmid41218870,
year = {2025},
author = {He, XY and Li, XH and Tong, ZH},
title = {[Cognitive impairment in long COVID: advances in pathological mechanisms and exercise rehabilitation interventions].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {11},
pages = {1087-1095},
doi = {10.3760/cma.j.cn112147-20250610-00315},
pmid = {41218870},
issn = {1001-0939},
support = {2023YFC0872500//National Key Research and Development Program/ ; Ggyfz202503//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; },
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/rehabilitation/etiology ; *Exercise Therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {Since the outbreak of the novel coronavirus (COVID-19) pandemic, long-term effects of the virus, known as long-COVID, has emerged. It is a chronic syndrome following infection. It is estimated that around 20% of COVID-19 survivors worldwide experience cognitive dysfunction. This is characterized by impairments in executive function, attention, memory, and other cognitive domains, and can have a significant impact on quality of life and social functioning. This article systematically reviewed recent studies and summarized the potential pathological mechanisms underlying cognitive dysfunction in long COVID, including neuroinflammation, glial cell dysregulation, involvement of the olfactory pathway and limbic system, autoimmunity and viral reactivation, cerebrovascular and blood-brain barrier damage, as well as abnormalities in neurotrophic factors and synaptic plasticity. Additionally, it explored the effects of exercise rehabilitation and multidimensional comprehensive rehabilitation strategies. The aim was to provide theoretical and scientific foundations for optimizing intervention programs for cognitive dysfunction in long COVID and for formulating clinical guidelines and public health policies.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Dysfunction/rehabilitation/etiology
*Exercise Therapy
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Quality of Life

@article {pmid41218624,
year = {2025},
author = {Gloeckl, R and Rischer, R and Schneeberger, T and Jarosch, I and Blome, C and Koczulla, R},
title = {[Healthcare Situation of 3,345 Long COVID Patients in Germany: Results of a Nationwide Survey].},
journal = {Pneumologie (Stuttgart, Germany)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2725-5650},
pmid = {41218624},
issn = {1438-8790},
abstract = {Long COVID includes persistent symptoms after SARS CoV 2 infection and leads to multiple physical and psychosocial burdens.Between March and April 2025, a nationwide sample of long COVID patients was recruited by means of an anonymous online survey. Demographic parameters, symptoms, use of outpatient/inpatient care services and subjective satisfaction with care were recorded.In total, 3345 people (average age 49 ± 13 years; 81.5% women) completed the survey. 83.8% reported a medically confirmed long COVID diagnosis, with a further 12.2% reporting a post-vac syndrome. The average duration of symptoms was 2.8 ± 1.1 years, with only 36.4% reporting an improvement in their symptoms over time. Almost nine out of ten patients (89.1%) were on long-term sick leave (average 1.8 ± 1.3 years), 70.8% reported total or partial incapacity for work and 46.4% applied for a pension. General practitioner care was the first point of contact for 75.7%. Over the course of the illness, 93% consulted more than three and 21.5% more than ten different doctors. Personal financial contributions were high: 41.4% invested more than € 1,000 and 11.3% more than € 10,000 in diagnostics or therapy. 60% received a rehabilitation intervention. Overall, 97.2% rated their care as "poor" or "very poor".This survey highlights a high and persistent burden among long COVID patients, as well as significant socioeconomic consequences, accompanied by a predominantly negative evaluation of the current care situation. Improvements require structured, easily accessible, and cross-sectoral services. Improving the primary care system, establishing clear referral pathways, and (where clinically indicated) integrating rehabilitative interventions into an interdisciplinary care concept could help to improve the care situation of patients with long COVID.},
}

@article {pmid41218055,
year = {2025},
author = {Panda, R and Mukherjee, R and Singh, K and Lahoti, S and Rai, AK and Verma, A and Bhalla, S and Chandwani, H and Rai, K and Mohapatra, A},
title = {Effects of the ECHO tele-mentoring program on Long COVID management in health facilities in India: A mixed-methods evaluation.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0331293},
pmid = {41218055},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/therapy/epidemiology ; India/epidemiology ; Female ; Male ; Telemedicine ; Middle Aged ; Adult ; SARS-CoV-2/isolation & purification ; *Mentoring/methods ; Health Facilities ; },
abstract = {BACKGROUND: Long COVID emerged as a significant long-term consequence of COVID-19 characterized by persistent symptoms post-infection. ECHO India initiated a training program across four states to enhance the capacity of medical officers (MOs) to manage long COVID syndrome. This study was undertaken to evaluate the effect of the ECHO tele-mentoring program on long COVID management in public health facilities in terms of change in knowledge, competence, and performance of the trained MOs.

METHODS: Mixed-methods approaches were adopted. Moore's Expanded Outcomes Framework was used for the study. Differences between the pre- and post-interventions were used to populate levels 1-5 of the framework with the trained MOs. This was supplemented by key informant interviews with stakeholders, i.e., trained MOs, hub leaders, and trainers. Level 6 was evaluated with patients seeking services for long COVID from the trained MOs. through quantitative exit interviews and in-depth interviews in two intervention states.

RESULTS: The pre-post analyses were conducted on a sample size of 204 MOs; a total of 420 beneficiary patients were surveyed. In-depth interviews were done with another 20 patients to measure satisfaction. The findings reveal a significant increase in the MOs' knowledge, learning, and competence. MOs expressed appreciation for the interactive nature of the tele-mentoring sessions and reported increased confidence in dealing with long COVID cases. The training improved the MOs' focus on mental health as a treatment strategy for long COVID. Patients interviewed expressed satisfaction with the care provided by the MOs, in particular with communication skills and the comprehensive approach adopted for long COVID management. They valued the information, the thorough examinations, and the recommendations given by the trained MOs.

CONCLUSION: The ECHO tele-mentoring program improved the knowledge and skills of primary care medical officers and also resulted in patient satisfaction.},
}

Humans
*COVID-19/therapy/epidemiology
India/epidemiology
Female
Male
Telemedicine
Middle Aged
Adult
SARS-CoV-2/isolation & purification
*Mentoring/methods
Health Facilities

@article {pmid41213692,
year = {2025},
author = {Billias, N and Pouliopoulou, DV and Lawson, A and D'Alessandro, V and Bryant, DM and Peters, S and Rushton, AB and Miller, E and Brunton, L and McGuire, S and Nicholson, M and Birmingham, TB and MacDermid, JC and Quinn, KL and Razak, F and Goulding, S and Galiatsatos, P and Saunders, E and Marsh, J and Pereira, TV and Bobos, P},
title = {Pursuing Reduction in Fatigue After COVID-19 via Exercise and Rehabilitation (PREFACER): a protocol for a randomised feasibility trial.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e102112},
pmid = {41213692},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/complications/rehabilitation ; *Fatigue/etiology/rehabilitation ; Feasibility Studies ; SARS-CoV-2 ; *Exercise Therapy/methods ; Randomized Controlled Trials as Topic ; Female ; },
abstract = {INTRODUCTION: Over 777 million COVID-19 infections have occurred globally, with data suggesting that 10%-20% of those infected develop Long COVID. Fatigue is one of the most common and disabling symptoms of Long COVID. We aim to assess the feasibility and safety of a new, remotely delivered, multimodal rehabilitation intervention, paced to prevent post-exertional malaise (PEM), to support the conduct of a future, definitive randomised trial.

METHODS AND ANALYSIS: We will conduct a randomised, two-arm feasibility trial (COVIDEx intervention vs usual care). Sixty participants with Long COVID will be recruited and randomised prior to giving informed consent under a modified Zelen design using 1:1 allocation with random permuted blocks via central randomisation to receive either the COVIDEx intervention or usual care. The 50-minute, remotely delivered, COVIDEx intervention will occur twice weekly for 8 weeks. All participants will wear a non-invasive device throughout their entire study participation, to track heart rate, blood oxygen saturation, steps, sleep and monitor PEM. The primary feasibility objectives will be recruitment rates, intervention fidelity, adherence, acceptability (intervention and design), retention, blinding success and outcome completeness. Secondary objectives will include refined estimates for the standard deviation and correlation between baseline and follow-up measurements of fatigue. Feasibility and clinical outcomes will be collected at baseline, 4, 8, 12 and 24 weeks. Qualitative interviews with participants and physiotherapists will explore intervention acceptability and barriers/facilitators.

ETHICS AND DISSEMINATION: Ethical approval for this study was obtained by the Western University Health Sciences Research Ethics Board (REB# 123902). Dissemination plans include sharing of trial findings at conferences and through open access publications and patient/community channels.

TRIAL REGISTRATION NUMBER: NCT06156176.},
}

Humans
*COVID-19/complications/rehabilitation
*Fatigue/etiology/rehabilitation
Feasibility Studies
SARS-CoV-2
*Exercise Therapy/methods
Randomized Controlled Trials as Topic
Female

@article {pmid41213281,
year = {2025},
author = {Goxhaj, L and McCorkell, L and van Rhijn-Brouwer, F and Soares, L and Vogel, JM and de Canson, C},
title = {Negative results in long COVID clinical trials: choosing outcome measures for a heterogeneous disease.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00665-6},
pmid = {41213281},
issn = {1474-4457},
}

@article {pmid41213124,
year = {2025},
author = {Berry, C and McKinley, G and Bayes, HK and Anderson, D and Lang, CC and Gill, A and Morrow, A and Sykes, R and Taggart, D and Kamdar, A and Welsh, P and Dawkes, S and McConnachie, A and Gray, SR},
title = {Resistance Exercise Therapy After COVID-19 Infection: A Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {8},
number = {11},
pages = {e2534304},
pmid = {41213124},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; *COVID-19/rehabilitation/therapy/psychology ; Middle Aged ; *Resistance Training/methods ; Quality of Life ; Adult ; SARS-CoV-2 ; Walk Test ; Aged ; Exercise Tolerance ; Treatment Outcome ; *Exercise Therapy/methods ; },
abstract = {IMPORTANCE: Long COVID presents an unmet therapeutic need.

OBJECTIVE: To determine the effects of a resistance exercise intervention on exercise capacity, health status, and safety among adults after COVID-19 infection.

A 2-arm, multicenter, randomized clinical trial including 233 adults with a hospital or community diagnosis of COVID-19 infection in the preceding 12 months was undertaken from June 1, 2021, to April 26, 2024. The intervention group comprised 117 individuals, and the control group comprised 116 individuals. A total of 224 individuals at baseline and 193 individuals at 3 months completed Incremental Shuttle Walk Tests.

EXPOSURES: The intervention group received the personalized resistance exercise intervention for 3 months, and the control group received treatment as usual.

MAIN OUTCOMES AND MEASURES: The primary outcome was the distance achieved (in meters) in the Incremental Shuttle Walk Test undertaken 3 months after randomization. Secondary outcome measures included health-related quality of life (measured by the European Quality of Life 5-Dimension 5-Level Instrument [EQ-5D-5L]), anxiety and depression (measured by the Patient Health Questionnaire), and grip strength.

RESULTS: A total of 233 adults (median age, 53.6 years [IQR, 43.8-60.8 years]; 146 women [62.7%]; 91 [39.1%] hospitalized with COVID-19 infection) were randomized (117 [50.2%] to the intervention group and 116 [49.8%] to the control group). The median percentage adherence with the exercise intervention was 71.0% (IQR, 47.8%-96.8%), equivalent to performing the exercises 5 days per week. The mean (SD) distance achieved in the Incremental Shuttle Walk Test was 328 (225) m for 224 individuals at baseline and 389 (249) m for 193 individuals at follow-up. The mean (SD) change in Incremental Shuttle Walk Test distance at 3 months compared with baseline was 83 (118) m in the intervention group (n = 94) and 47 (95) m in the control group (n = 98) (adjusted mean difference, 36.5 m [95% CI, 6.6-66.3 m]; P = .02). By 3 months, compared with the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 [95% CI, 0.01-0.11]; P = .02), Patient Health Questionnaire category (0.5 [95% CI, 0.2-0.8]; P = .01), and handgrip strength (2.6 kg [95% CI, 0.9-4.2 kg]; P = .002).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a 3-month program of resistance exercise among adults after COVID-19 infection appeared to improve walking distance, health-related quality of life, anxiety, depression, and grip strength. This pragmatic intervention may be a generalizable therapy for individuals with persisting physical symptoms after COVID-19 infection.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04900961.},
}

Humans
Female
Male
*COVID-19/rehabilitation/therapy/psychology
Middle Aged
*Resistance Training/methods
Quality of Life
Adult
SARS-CoV-2
Walk Test
Aged
Exercise Tolerance
Treatment Outcome
*Exercise Therapy/methods

@article {pmid41212631,
year = {2025},
author = {Goodfellow, H and Blandford, A and Bradbury, K and Gomes, M and Hamilton, F and Henley, W and Stevenson, F and Fernandez-Reyes, D and Hurst, J and Heightman, M and Pfeffer, P and Ricketts, W and Singh, R and Hylton, H and Linke, S and Bindman, J and Robson, C and Walker, S and Ismaila, H},
title = {Development and implementation of a digital health intervention in routine care for long COVID patients: a comprehensive synopsis.},
journal = {Health and social care delivery research},
volume = {13},
number = {39},
pages = {1-27},
doi = {10.3310/GJHG0331},
pmid = {41212631},
issn = {2755-0079},
mesh = {Humans ; *COVID-19/rehabilitation ; Male ; Female ; Telemedicine/organization & administration ; Middle Aged ; SARS-CoV-2 ; Adult ; Patient Reported Outcome Measures ; United Kingdom ; Aged ; State Medicine ; Digital Health ; },
abstract = {BACKGROUND: By July 2020, large numbers of post-COVID patients were experiencing symptoms for weeks or months, but traditional National Health Service models of rehabilitation service delivery could not meet demand.

OBJECTIVES: Design and deploy a digital health intervention to provide digitally delivered, remotely supported rehabilitation to long COVID patients on complicated and evolving pathways.

METHODS: The multidisciplinary team combined established research methods based on engineering and computer science (considering safety, stability and user requirements) with those based on biomedical and health service research (considering effectiveness and population impact). Qualitative data comprised recordings of meetings between study team members and clinicians and semistructured interviews with clinician and patient users. Quantitative data comprised referral, registration and usage rates; demographic and clinical characteristics of patients; and patient-reported outcome measures.

RESULTS: We created a modifiable digital health intervention, 'Living With COVID Recovery[TM] developed by Living With Ltd', London, UK, that continues to be used by National Health Service trusts. The digital health intervention included integration into a clinical pathway, a clinician-facing dashboard, two-way messaging and a patient-facing app with information and evidence-based treatments. We aimed to register 1000 users. By study completion on 20 December 2022, there were 9781 patients invited, of whom 7679 (78.5%) had registered, at 33 National Health Service clinics.

LIMITATIONS: Data came from patients at long COVID clinics, however data were unlikely to be representative of people with long COVID. We could not observe clinics under lockdown and had limited access to patient digital health intervention users or to people not engaging with the digital health intervention. Patient user data were incomplete, with inconsistent patient-reported outcome measure and other questionnaire data completion and no data on initial severity of disease, vaccination status, comorbidities or other individual circumstances.

CONCLUSIONS: Long COVID can be extremely debilitating, comparable to stage IV lung cancer in relation to fatigue and health-related quality of life. Care and rehabilitation should address the management of fatigue and reflect the impact of social disadvantage on symptom severity. With sufficient resources, a digital health intervention can be developed quickly and effectively using agile methodology and bringing together a genuinely multidisciplinary team, including, importantly, an industry partner. Digital health intervention product design and deployment are both important in getting National Health Service trusts, healthcare professionals and patients to engage with a digital health intervention. Projects should work closely with all user groups. Lockdown and the unmet need of a new patient group encouraged those who might otherwise have been reluctant to try a digital health intervention. Many patients and clinics accepted this digital remote support, which helped patients feel cared for while reducing strain on health services. This may encourage acceptance of other digital health intervention, although medical record integration remains a deterrent to clinics.

FUTURE WORK: This research focused on the development, deployment and evaluation of a digitally enabled rehabilitation programme for long COVID. Clinical effectiveness will be assessed within the Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways (UCL, London, UK) study.

FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132243.},
}

Humans
*COVID-19/rehabilitation
Male
Female
Telemedicine/organization & administration
Middle Aged
SARS-CoV-2
Adult
Patient Reported Outcome Measures
United Kingdom
Aged
State Medicine
Digital Health

@article {pmid41212544,
year = {2025},
author = {Knopman, DS and Koltai, D and Laskowitz, D and Becker, J and Charvet, L and Wisnivesky, J and Federman, A and Silverstein, A and Lokhnygina, Y and Pilloni, G and Haddad, M and Mahncke, H and Van Vleet, T and Huang, R and Cox, W and Terry, D and Karwowski, J and McCray, N and Lin, JJ and McComsey, GA and Singh, U and Geng, LN and Chu, HY and Reece, R and Moy, J and Arvanitakis, Z and Parthasarathy, S and Patterson, TF and Gupta, A and Ostrosky-Zeichner, L and Parsonnet, J and Kiriakopoulos, ET and Fong, TG and Mullington, J and Jolley, S and Shah, NS and Morimoto, SS and Lee-Iannotti, JK and Killgore, WDS and Dwyer, B and Stringer, W and Isache, C and Frontera, JA and Krishnan, JA and O'Steen, A and James, M and Harper, BL and Zimmerman, KO and , },
title = {Evaluation of Interventions for Cognitive Symptoms in Long COVID: A Randomized Clinical Trial.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
pmid = {41212544},
issn = {2168-6157},
abstract = {IMPORTANCE: Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need.

OBJECTIVE: To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID.

This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID.

INTERVENTIONS: Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks.

MAIN OUTCOMES AND MEASURES: Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days.

RESULTS: A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, -0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, -0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, -0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, -0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions.

CONCLUSIONS AND RELEVANCE: This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05965739.},
}

@article {pmid41210966,
year = {2025},
author = {Poyatos, P and Gratacós, M and Aguilar, D and Luque, N and Bonnin-Vilaplana, M and Eizaguirre, S and Cascante, M and Orriols, R and Tura-Ceide, O},
title = {Transcriptomic profiling of endothelial progenitor cells in post-COVID-19 patients: Insights at 3 and 6-month post-infection.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113731},
pmid = {41210966},
issn = {2589-0042},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant global morbidity since 2019. Long COVID, characterized by persistent symptoms after acute infection, may involve endothelial injury. We analyzed endothelial colony-forming cells (ECFCs) from post-COVID-19 patients at 3- and 6-month post-infection, comparing them with healthy controls and stratifying by prior pulmonary embolism (PE). Transcriptomic profiling identified differentially expressed genes (DEGs) associated with endothelial homeostasis, inflammation, oxidative stress, and thrombosis. Post-COVID ECFCs showed downregulation of NOS3, KLF2, ANGPT1, PIK3R3, GBX2, GDF6, SMAD6, SRC, and TGFB1, and upregulation of CASP1, CXCL5, IL12A, SOD2, TIMP3, and TLR2. Minimal differences were observed between 3 and 6-month samples. PE patients showed downregulation of thrombosis-related genes such as PTGS2 and ACKR3. These findings indicate sustained endothelial dysfunction and inflammation up to 6 months post-infection, highlighting the importance of long-term monitoring and potential therapeutic strategies to support vascular health in post-COVID-19 patients.},
}

@article {pmid41206715,
year = {2025},
author = {Wegwarth, O and Hertwig, R},
title = {Short report: association between self-reported COVID-19 experience and contemptuous beliefs about pandemic management among German citizens and healthcare professionals.},
journal = {Journal of public health (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/pubmed/fdaf144},
pmid = {41206715},
issn = {1741-3850},
support = {//Siemens Caring Hands e.V./ ; },
abstract = {BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of public adherence to pandemic management measures. Contempt for these measures could undermine compliance in future pandemics. This study explored associations between self-reported COVID-19 experiences and contemptuous beliefs about COVID-19 pandemic management.

METHODS: A cross-sectional online survey study was conducted in September 2024 with 964 German citizens and 423 healthcare professionals from respondi panels (Cologne, Germany). Respondents reported their attitudes toward eight contemptuous statements regarding COVID-19 pandemic management and their personal COVID-19 experiences, including infection, vaccine side effects, long COVID, and patient care (for professionals). Associations were analyzed using logistic regression and Mann-Whitney U tests.

RESULTS: Citizens with self-reported experience of COVID-19 infections were less likely to hold contemptuous beliefs (OR: 0.58; 95% CI: 0.39-0.85; P = .005), while those with experience of vaccine side effects were considerably more likely (OR: 1.50; 95% CI: 1.10-1.92; P = .009). Long COVID had no significant effect. Among professionals, not having cared for COVID-19 patients doubled the likelihood of contempt (OR: 2.10; 95% CI: 1.28-3.45; P = .003).

CONCLUSION: Findings suggest that experiential factors may contribute to belief formation-an area with limited empirical attention but potential relevance for addressing societal polarization.},
}

@article {pmid41205594,
year = {2025},
author = {Shahbaz, S and Osman, M and Syed, H and Mason, A and Rosychuk, RJ and Cohen Tervaert, JW and Elahi, S},
title = {Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102449},
doi = {10.1016/j.xcrm.2025.102449},
pmid = {41205594},
issn = {2666-3791},
abstract = {Long COVID (LC) manifests with sex-specific differences, particularly in those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study reveals that female LC patients (LCF) with ME/CFS show a shift toward myelopoiesis, reduced lymphocytes, increased neutrophils/monocytes, and depleted regulatory T cells-suggesting persistent immune activation. Elevated CD71[+] erythroid cells and disrupted erythropoiesis contribute to fatigue and tissue damage in LCF. Cytokine profiling indicates a stronger pro-inflammatory response in LCF compared to males (LCM), along with markers of gut barrier dysfunction. Hormonal analysis shows reduced testosterone in LCF and estradiol in LCM. Transcriptomic data reveal neuroinflammatory signatures in LCF, potentially explaining cognitive symptoms. We also identify biomarkers that distinguish LCF from LCM and correlate with sex-specific clinical symptoms. Overall, LC with ME/CFS is characterized by sex-specific immune, hormonal, and transcriptional alterations, with females exhibiting more severe inflammation. These insights underscore the need for sex-tailored interventions, including consideration of hormone replacement therapy.},
}

@article {pmid41204293,
year = {2025},
author = {Prasad, PA and Hubbard, CC and Cenzer, I and Boscardin, J and Weerahandi, H},
title = {Health service use and work related outcomes in older adults with functional and cognitive impairments during the COVID-19 pandemic.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3846},
pmid = {41204293},
issn = {1471-2458},
support = {Project ID140673V//California Department of Public Health CPR3 program/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Aged ; Longitudinal Studies ; *Cognitive Dysfunction/epidemiology ; Middle Aged ; *Functional Status ; *Patient Acceptance of Health Care/statistics & numerical data ; Pandemics ; SARS-CoV-2 ; },
abstract = {BACKGROUND: The COVID-19 pandemic had a lasting global health impact, with many survivors facing Long Covid. Older adults, already vulnerable to disability and cognitive decline, may also experience long-term challenges after COVID-19 infection. This study explores whether a history of COVID-19 infection interacts with pre-existing impairments in older adults, focusing on its effects on health services and work-related outcomes.

METHODS: This longitudinal cohort study used data from the Health and Retirement Study (HRS), spanning 2018 to 2022. Participants ≥ 50 years old in 2018 with documented functional and cognitive status scores and self-reported presence or absence of COVID-19 infection were included. Functional status was assessed using the Functional Limitation score, and cognitive status using the Crimmins cognitive scale or Langa scale if the HRS respondents were represented by a proxy. Health services use and work outcomes were evaluated using the 2022 HRS survey. Multivariable logistic regression models examined the association between baseline functional and cognitive status and outcomes, controlling for COVID-19 history, 2018 functional or cognitive status, age, gender, marital status, number of chronic conditions, household size, graduation from high school, and self-report of COVID-19 vaccination.

RESULTS: The study included 8,621 respondents. Those with severe functional limitations in 2018 were more likely to report health services use in 2022, irrespective of COVID-19 history. COVID-19 history did not significantly interact with baseline functional or cognitive impairments when evaluating health services use, ability to work, or disability benefit access. While older adults with moderate or severe functional limitations were more likely to report hospitalizations and nursing home stays, these outcomes were not significantly different based on COVID-19 history.

CONCLUSIONS: In this cohort of older adults, the relationship between baseline functional and cognitive impairment with health services use, ability to work, or disability benefit access did not significantly vary by self-reported COVID-19 infection history. While COVID-19 may have long-term impacts on older populations, our data suggest that infection history alone did not amplify the effects of pre-existing impairments in those who survived the pandemic. Further research using validated measures of persistent symptoms is needed to understand how Long Covid may manifest in older adults.},
}

Humans
*COVID-19/epidemiology
Male
Female
Aged
Longitudinal Studies
*Cognitive Dysfunction/epidemiology
Middle Aged
*Functional Status
*Patient Acceptance of Health Care/statistics & numerical data
Pandemics
SARS-CoV-2

@article {pmid41204118,
year = {2025},
author = {Scolari, FL and Spinardi, J and Silva, MMDD and Trott, G and Rodrigues, CO and Rover, MM and Souza, EM and Manfio, JL and Camargo, NI and Souza, AP and Souza, D and Carli, RF and Roldão, ES and Mocellin, D and Miozzo, AP and Silva, GND and Souza, JMB and Santos, RDRMD and Itaqui, CR and Rech, GS and Irineu, VM and Francisco, SC and Silvestre, O and Neves, PDMM and Tramujas, L and Nobre, V and Carvalho, SM and Ferreira, CDDA and Oliveira, JC and Royer, CA and Luiz, RM and Baura, VA and Gradia, DF and Brandalize, APC and Pereira, HA and Poitevin, CG and Robinson, CC and Barreto, BB and Schvartzman, PR and Marcolino, M and Antonio, ACP and Polanczyk, CA and Maccari, JG and Nasi, LA and Valluri, SR and Julião, VW and d'Hellencourt, FL and Kyaw, MH and Castillo, GDCM and Falavigna, M and Rosa, RG},
title = {Impact of long COVID phenotypes on quality of life following symptomatic omicron infection in Brazil: a machine learning analysis.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1523},
pmid = {41204118},
issn = {1471-2334},
mesh = {Humans ; Female ; Brazil/epidemiology ; *COVID-19/epidemiology/psychology/virology ; *Quality of Life ; Male ; Adult ; *Machine Learning ; Middle Aged ; Prospective Studies ; Phenotype ; SARS-CoV-2 ; Aged ; },
abstract = {BACKGROUND: This study aimed to identify phenotypes of long COVID symptoms in adults following Omicron infection and assess their association with health-related quality of life (HRQoL).

METHODS: We analyzed three prospective observational studies in Brazil, enrolling adult patients who sought care for symptomatic Omicron infection between December 2021 and March 2023. The infection was confirmed by either an antigen test or reverse transcriptase polymerase chain reaction. Long COVID symptoms were assessed three months after enrollment through structured interviews. Phenotypes of Long COVID-19 were identified using a machine learning-based clustering approach. Exploratory analyses were conducted to examine predisposing factors and health-related quality of life utilities, measured by EQ-5D-3 L, associated with each phenotype.

RESULTS: A total of 2,989 patients were analyzed (39% women, median age 41 years, and 96% had completed the primary series of COVID-19 vaccination). Long COVID symptoms at three months were reported by 1,155 (38.6%) patients. Three phenotypes were identified: cluster 1 (n = 459 [39.7%]), characterized by a median of three symptoms (IQR, 2-5) with memory loss (80.4%), concentration problems (38.3%) and fatigue (35.7%) being most common; cluster 2 (n = 549 [47.5%]), characterized by a median of two symptoms (IQR, 1-4) with fatigue (43.7%), other symptoms (42.3%), and cough (20.6%) being most common; and cluster 3 (n = 147, 12.7%), characterized by a higher number of symptoms (median, 8; IQR, 7-10), with fatigue (89.9%), memory loss (88.4%), and anxiety (64.6%) as the most common. The mean EQ-5D-3 L utility at 3 months was 0.75 for cluster 1, 0.73 for cluster 2, and 0.59 for cluster 3 (p < 0.001). After adjusted regression analysis, cluster 3 was independently associated with the lowest EQ-5D-3 L utilities (mean difference, -0.21; 95%CI, -0.24 to -0.18; p < 0.001).

CONCLUSIONS: Distinct phenotypic presentations of Long COVID following Omicron infection in Brazil were identified, with significant differences in quality of life.

CLINICAL TRIAL NUMBER: Not applicable.},
}

Humans
Female
Brazil/epidemiology
*COVID-19/epidemiology/psychology/virology
*Quality of Life
Male
Adult
*Machine Learning
Middle Aged
Prospective Studies
Phenotype
SARS-CoV-2
Aged

@article {pmid41204001,
year = {2025},
author = {Kuodi, P and Shibli, H and Zayyad, H and Wertheim, O and Wiegler, KB and Jabal, KA and Dror, AA and Nazzal, S and Glikman, D and Charlett, A and Edelstein, M},
title = {Optimizing the schedule of BNT162b2 COVID-19 against long COVID and associated quality of life losses.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {462},
pmid = {41204001},
issn = {2730-664X},
abstract = {BACKGROUND: The long-term impact of COVID-19 vaccination on post-acute COVID-19 symptoms and associated quality of life (QoL) changes remains incompletely described. This study aimed to explore the impact of the timing of COVID-19 priming and booster doses, on reporting long COVID symptoms and associated QoL changes.

METHODS: Individuals who had PCR testing for SARS-CoV-2 processed in government hospitals in Northern Israel between 15[th] March 2021 and 15[th] June 2022 were invited to answer serial online surveys collecting information on SARS-CoV-2 infection, vaccination status and post-acute symptoms every 3-4 months for two years. Participants were categorized into groups based on the number of doses received prior to infection. We compared these groups over time in terms of reporting post-COVID symptom clusters and QoL, using population-average and mixed-effects regression models, respectively.

RESULTS: A total of 4809 individuals are enrolled and respond to up to five follow-up surveys. Of these, 1377 (28.61%) report a positive SARS-CoV-2 test, while 3432 (71.39%) report a negative result. After adjustment for potential confounders, receiving at least three COVID-19 vaccine doses prior to infection is associated with a 34% reduction in the likelihood of reporting at least one long COVID symptom cluster compared to being unvaccinated (adjusted odds ratio [aOR] = 0.66, p = 0.022). Pre-infection vaccination is also associated with higher quality of life (QoL) scores (β = 0.07, p < 0.001). The estimated vaccine effectiveness of three pre-infection doses against long COVID over a two-year period is 26.5% (95% CI: 10.8-39.4). This protective effect remains stable over time. In contrast, vaccination received after infection shows no association with long COVID symptoms or QoL outcomes.

CONCLUSIONS: Receiving at least three COVID-19 vaccine doses prior to SARS-CoV-2 infection provides a sustained protective effect against long COVID and its negative impact on quality of life for at least two years. The longer-term durability of this protection, the role of reinfection, and the influence of emerging viral variants remains to be investigated.},
}

@article {pmid41202576,
year = {2025},
author = {Rottstädt, F and König, L and Seifert, C and Jesgarzewsky, T and Finke, K and Reuken, P and Stallmach, A and Vonderlind, S and Croy, I},
title = {Reduced interpersonal touch and elevated preferred interpersonal distance are signs of impaired social contact behavior in post-COVID syndrome.},
journal = {Journal of psychosomatic research},
volume = {199},
number = {},
pages = {112438},
doi = {10.1016/j.jpsychores.2025.112438},
pmid = {41202576},
issn = {1879-1360},
abstract = {BACKGROUND: Increased inflammation often evokes an adaptive sickness behavior with social withdrawal. We aimed to test whether reduced social contact also characterizes Post-COVID syndrome, a condition that is hypothesized to involve prolonged inflammation following SARS-CoV-2 infection.

METHODS: We queried 49 Post-COVID patients (mean age = 46.8 years, 38 (77.6 %) female, mean duration of disease = 16 months) and 49 age- and gender-matched healthy control paricipants for their satisfaction with socializing, frequency of interpersonal contact and touch, and preferred interpersonal distance. Additionally, severity of fatigue and depressive mood were assessed in all participants.

RESULTS: While Post-COVID patients did not differ significantly from healthy controls in the frequency of general interpersonal contact, they reported a markedly lowered satisfaction with socializing (p < .01, η[2] = 0.27). Specifically, touch frequency and desire for touch were reduced, with the largest difference observed for interactions with friends (p < .001, η[2] = 0.13). Furthermore, Post-COVID patients reported approximately a 50 % increase in preferred interpersonal distance towards others in order to feel comfortable (p < .001, η[2] = 0.17). Mediation analyses suggest that those deviations were primarily driven by fatigue rather than depressive symptoms in Post COVID patients.

CONCLUSIONS: Over the course of the disease, the observed impairments are concerning, as they deprive patients of social contact as a source of dyadic coping and mental health. Pacing strategies should be adapted to explicitly incorporate social contact as a key element. The findings also align with the sickness behavior theory.},
}

@article {pmid41202571,
year = {2025},
author = {Ahmed, S and Greenberg, J and Kenney, R and Marini, C and Hyman, S and Fung, S and Edeoga, N and Baltazar, M and Grossman, SN and Seixas, A and Jean-Louis, G and Osorio, RS and Condos, R and Frontera, J and Gonzalez-Duarte Briseno, MA and Galetta, SL and Balcer, LJ and Thawani, SP},
title = {Autonomic dysfunction and quality of life in a cohort of neurology outpatients with post-acute sequelae of COVID-19, a two-year follow-up study.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {143},
number = {},
pages = {111719},
doi = {10.1016/j.jocn.2025.111719},
pmid = {41202571},
issn = {1532-2653},
abstract = {PURPOSE: Many studies estimate that more than 50% of non-hospitalized patients with long-COVID develop moderate to severe autonomic dysfunction. However, the specific impact of autonomic dysfunction as it relates to quality of life in long-COVID is not fully understood. The aim of the current study is to assess autonomic symptoms and quality-of-life in patients with Post-Acute Sequelae of COVID-19 (PASC) recruited from a neurology department outpatient setting.

METHODOLOGY: In a two-year follow-up study of a baseline cohort of 93 non-hospitalized SARS-CoV-2 laboratory-positive patients evaluated for PASC between November 2020-August 2021, 44 participants completed follow-up telephone questionnaires examining quality-of-life as well as neurologic and autonomic symptoms.

RESULTS: Among 93 participants, 44 (47 %) completed the two-year follow-up evaluation and 27 (61 %) were female with a median age of 55 years (IQR = 24-88). Most participants (95 %, 42/44) were vaccinated against COVID-19 and 43 % (19/44) had a pre-existing neurological disorder. Median time from index COVID-19 infection to follow-up was 26 months (IQR = 23-17), with a median of 15 months (IQR = 15-16) between visits. Fatigue, word finding difficulty, and changes in memory were the most commonly reported PASC symptoms. Sixty-six percent (29/44) of individuals met criteria for autonomic dysfunction as defined by the Composite Autonomic Symptom Score-31 (COMPASS-31) scale. Secretomotor and gastrointestinal subdomains demonstrated significant associations with Neuro-QoL metrics for Anxiety, Depression, and Fatigue. For every 1 additional PASC symptom reported at a follow-up study visit, there was an average increase of 1.5 points on the COMPASS-31 composite score. In addition, visual disturbances and sleep impairment were both associated with increased autonomic dysfunction.

CONCLUSION: The strong association between autonomic dysfunction and reduced QoL in PASC and the relation to insomnia, visual dysfunction, and functional impairment are valuable findings, reinforcing the clinical impact of these symptoms longitudinally after index COVID-19 infection.},
}

@article {pmid41201746,
year = {2025},
author = {Wander, PL and Awan, O and Neal, J and Seidel, I and Bell, KA and Cassell, A and Fattal, D and Ng, B and Pyne, ML and Rog, L and Helfand, M},
title = {Synopsis of 2024 VA Long COVID Clinical Guidance for U.S. Veterans: Part 1, Nervous System-Related Symptoms.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-09829-4},
pmid = {41201746},
issn = {1525-1497},
abstract = {DESCRIPTION: Long COVID is common and includes nervous system-related symptoms (e.g., autonomic dysfunction, cognitive impairment, fatigue, and pain). We sought to develop just-in-time evidence-informed guidance for nervous system-related Long COVID, a condition for which mature evidence is limited.

METHODS: The U.S. Veterans Affairs (VA) Veterans Health Administration (VHA) Long COVID Field Advisory Board commissioned an expert panel that worked with a GRADE methodologist to develop an evidence-to-decision framework for emergent conditions by applying core elements of the Standards for Developing Trustworthy Clinical Practice Guidelines and those of GRADE. We also convened a multidisciplinary writing group that identified a list of clinically relevant questions and commissioned an independent review and synthesis of existing evidence. The writing group conducted structured discussions and used this evidence base to make recommendations for evaluation and treatment ("Evidence-informed Recommendations"). For history-taking, physical exam, and commonly used, noninvasive diagnostic tests, statements were based on consensus determinations of useful and safe care ("Good Practice Statements"). We used a Whole Health Systems approach to support the development of guidance that was patient-centered, culturally appropriate, and available regardless of literacy or disability. Feedback was solicited from Veterans and other stakeholders. Where the published literature was insufficient, we used evidence from treatment of similar conditions.

RECOMMENDATIONS: We drafted 30 Evidence-informed Recommendations and 41 Good Practice Statements for nervous system-related Long COVID in Veterans and disseminated them VA-wide, targeting specialty care providers. More research on the effectiveness of diagnostic and therapeutic interventions is needed. In particular, evidence "borrowed" from other conditions and populations should be replaced or supplemented by evidence in Long COVID. Clinical guidance should be updated as this evidence becomes available.

KEY POINTS: QUESTION: How can clinicians provide evidence-informed care for nervous system-related Long COVID (e.g., autonomic dysfunction, cognitive impairment, fatigue, and pain)?

FINDINGS: We commissioned an independent rapid evidence review which found that evidence supporting the care of nervous system-related Long COVID symptoms was limited. Using available evidence and other considerations (e.g., costs, equity, and applicability to Veterans experiencing Long COVID), we drafted 30 Evidence-informed Recommendations and 41 Good Practice Statements for nervous system-related Long COVID.

MEANING: Although mature evidence was limited, this guidance can provide a framework for clinicians caring for patients with nervous system-related Long COVID. More research on the effectiveness of diagnostic and therapeutic interventions in Long COVID is needed.},
}

@article {pmid41200182,
year = {2025},
author = {Liu, H and Xu, Z and Karsidag, I and Wang, P and Weng, J},
title = {Immune cell communication networks and memory CD8[+] T cell signatures sustaining chronic inflammation in COVID-19 and Long COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1689507},
pmid = {41200182},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *CD8-Positive T-Lymphocytes/immunology ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; *Cell Communication/immunology ; Female ; Male ; *Immunologic Memory ; Middle Aged ; Chronic Disease ; Single-Cell Analysis ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: COVID-19, including its post-acute sequelae (Long COVID), is increasingly recognized as involving persistent immune dysregulation and chronic inflammation. Severe and prolonged disease states are often accompanied by sustained cytokine release, immune cell exhaustion, and ongoing cell-cell communication that shapes the inflammatory milieu. Among immune subsets, CD8[+] T cells play a central role in antiviral defense, yet the molecular mechanisms linking their dysfunction to prolonged inflammation remain incompletely understood.

METHODS: We analyzed 73,110 peripheral blood mononuclear cells (PBMCs) from individuals across four disease states (Healthy, Exposed, Infected, and Hospitalized) using single-cell RNA sequencing. Immune cell subsets were annotated, and T cell heterogeneity was profiled. Cytokine and inflammatory scores were calculated to assess immune activation. Differentially expressed genes (DEGs) underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Cell-cell communication was evaluated to map ligand-receptor networks. Additionally, nine machine learning models were trained on a bulk RNA-seq cohort, and the SHapley Additive exPlanations (SHAP) framework was applied to interpret key predictive genes.

RESULTS: Progressive disease severity was associated with a decline in T cell proportions, enrichment of pro-inflammatory myeloid cells, and elevated cytokine expression, particularly IL-32. Memory CD8[+] T cells showed increased exhaustion and inflammatory scores while maintaining a central position in MHC-I-mediated communication networks. Persistent activation of immune and metabolic pathways, including antigen presentation and oxidative phosphorylation, was observed in prolonged disease states. Seven genes (RPS26, RPS29, RPL36, RPL39, RPS28, RPS21, and CD3E) were identified as strong predictors of chronic immune dysregulation, with the XGBoost model achieving the highest AUC. SHAP analysis confirmed their contributions to disease classification.

CONCLUSION: This study maps the immune landscape of COVID-19 and Long COVID at single-cell resolution, revealing that persistent immune cell communication, particularly involving memory CD8[+] T cells, may sustain chronic inflammation beyond the acute phase. The identified molecular signatures offer potential biomarkers and therapeutic targets for mitigating post-viral inflammatory syndromes.},
}

Humans
*COVID-19/immunology
*CD8-Positive T-Lymphocytes/immunology
*SARS-CoV-2/immunology
*Inflammation/immunology
*Cell Communication/immunology
Female
Male
*Immunologic Memory
Middle Aged
Chronic Disease
Single-Cell Analysis
Post-Acute COVID-19 Syndrome

@article {pmid41200018,
year = {2025},
author = {Feldman, C and Manentsa, N and Akpomiemie, G and Jabavu, A and Moller, K and Baskhar, E and Mtshazo, B and Edem, E and Sokhela, SM and Lalla-Edward, ST and Venter, WDF and Richards, GA},
title = {Pulmonary manifestations of long COVID in Johannesburg, South Africa.},
journal = {Southern African journal of infectious diseases},
volume = {40},
number = {1},
pages = {734},
pmid = {41200018},
issn = {2313-1810},
abstract = {BACKGROUND: There are few studies of long coronavirus disease (COVID) in low- and middle-income countries.

OBJECTIVES: This study investigated long-term pulmonary manifestations of long COVID among adults in Johannesburg, South Africa.

METHOD: This was a respiratory sub-study of a larger long COVID investigation. Cases with self-reported long COVID symptoms were recruited into four cohorts: prior asymptomatic infection, mild to moderate infection, hospitalised for severe infection and vaccinated prior to infection. Cases with respiratory comorbidity and/or well-characterised exposure to certain conditions (e.g. cigarette smoking) were excluded. Demographics, clinical features, spirometry, six-minute walk test (6MWT) and high-resolution computerised tomographic (HRCT) scan of the chest were recorded.

RESULTS: Of the 171 patients interviewed from the initial study, 36 with appropriate inclusion criteria were recruited a median of 2.1 years following their acute COVID-19 illness. Accordingly, the incidence of long COVID was 21.1% (36/171 patients) for the group as a whole and 5.9% (3/51), 25.0% (14/56), 37.8% (17/45) and 10.5% (2/19) for cohorts 1-4, respectively (p = 0.001). The major symptoms were tiredness and/or fatigue, shortness of breath and cough. Overall, 33 patients had abnormal 6MWT results, and 10 had abnormalities on spirometry; obstructive pattern in five, restrictive in three and mixed in two. Seven patients (six of whom were previously hospitalised) had probable/possible abnormalities compatible with long COVID on HRCT scan (p = 0.045).

CONCLUSION: This study documented respiratory abnormalities in patients as long as 2 years after prior SARS-CoV-2 infection, especially among those with severe prior infection.

CONTRIBUTION: This was among the first studies comprehensively documenting pulmonary abnormalities in patients with long COVID in South Africa.},
}

@article {pmid41199609,
year = {2025},
author = {Lee, C and Williams, P and Abrahams, A and Darbyshire, J and Davies, HE and De Kock, J and Esmer, U and Jones, SA and Newey, V and Scott, J and Smith, N and Winch, D and Master, H and Elkin, S and , },
title = {What Can We Learn Four Years On? A Multi-Centre Service Evaluation Exploring Symptoms, Functional Impact, Recovery and Care Pathways in Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70435},
pmid = {41199609},
issn = {1369-7625},
support = {//This study is independent research funded by the National Institute for Health and Care Research (NIHR) (LOng COvid Multidisciplinary consortium: Optimising Treatments and servIces acrOss the NHS [LOCOMOTION], Ref: COV-LT2-0016)./ ; },
mesh = {Humans ; Female ; *COVID-19/complications/therapy/psychology ; Male ; Middle Aged ; England ; Adult ; Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; Wales ; Activities of Daily Living ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long Covid (LC) is associated with long-term health impacts that require ongoing support from healthcare services. We aimed to gain insights into patients' perceptions of their ongoing symptoms of LC, the effect on daily living and vocation, perceptions of what helps with LC recovery, as well as LC care pathways and ongoing care needs.

METHODS: An online survey was sent to 513 participants who had used one of three LC services across England and Wales between 2020 and 2024. Participants were invited to share their experiences. We employed a mixed-methods approach for data analysis, synthesising findings from quantitative and qualitative data. All data shared between sites was de-identified.

RESULTS: 269 (52.4%) participants completed the survey. The mean age was 52.7 (sd ± 12.0), 69.1% female and 55.0% were White-British. The mean duration since initial SARS-CoV-2 infection was over 3 years (1204.4 ± 275.7 days). The Post-Covid Functional Status (PCFS) scale indicated that most participants (94.1%, n = 253) had not fully recovered. When employing a global rate of change scale, 39.0% (n = 96) of 246 responders indicated they are still making improvements with respect to their recovery; 40.7% (n = 100) had plateaued, and 20.3% (n = 50) reported a worsening trajectory. Those with ongoing symptoms described fatigue 83.0% (n = 210), cognitive dysfunction 58.5% (n = 148) and breathlessness or wheezing 43.9% (n = 111) most frequently. Of those who responded, 20.8% (n = 48) were 'working as prior to their initial LC infection' and 25.5% (n = 59) were currently 'unable to work'. Almost half (44.3%; n = 86) were no longer receiving care whilst also reporting unmet care needs. In total, 62.7% (n = 126) of participants indicated unmet care needs, and qualitative analysis indicated five overarching domains as having an important impact on long-term LC recovery and ongoing healthcare needs. These were Living with LC, LC interventions and recovery, Approach to the delivery of care, Insufficient support and Suggestions and improvement.

CONCLUSION: This study indicates the extent to which individuals continue to experience ongoing symptoms of LC, including aspects related to recovery and vocational impact, highlighting the potential widening gap between the ongoing need to support those living with LC and the limited provision of care.

The survey was co-produced with Experts by Experience, who had previously attended an LC service and members of the Patient Advisory Group within the Locomotion Consortium. Collaboration and involvement continued throughout the study, including analysis, interpretation and writing processes.

CLINICAL TRIAL REGISTRATION: Study registration details are available at ClinicalTrials.gov: NCT05057260 and ISRCTN: 15022307.},
}

Humans
Female
*COVID-19/complications/therapy/psychology
Male
Middle Aged
England
Adult
Aged
Surveys and Questionnaires
SARS-CoV-2
Wales
Activities of Daily Living
Post-Acute COVID-19 Syndrome

@article {pmid41199272,
year = {2025},
author = {Blomberg, B and Myklebust, NN and Oppegaard, O and Tøndel, C and Cox, RJ and Iversen, A and Lehmann, ME and Sandvig, A and Dahl, TB and Valderhaug, VD and Szodoray, P and Wilhelmsen, M and Kirsebom, BE and Glambek, M and Kaarbøe, O and Aukrust, P and Lie, RT and Langeland, N},
title = {Randomized trial of nirmatrelvir/ritonavir versus placebo for adults with acute COVID-19 to prevent long COVID: PanoramicNOR Trial.},
journal = {Trials},
volume = {26},
number = {1},
pages = {477},
pmid = {41199272},
issn = {1745-6215},
mesh = {Humans ; *Ritonavir/administration & dosage/therapeutic use/adverse effects ; Adult ; Double-Blind Method ; *COVID-19 Drug Treatment ; *COVID-19/prevention & control/complications ; *Antiviral Agents/administration & dosage/therapeutic use/adverse effects ; Middle Aged ; Young Adult ; Adolescent ; Male ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Female ; Drug Combinations ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: The high prevalence of long-term persisting symptoms after COVID-19 (coronavirus disease 2019), termed long COVID or post-COVID-19 condition, even among those with mild initial disease, may have a large public health impact. Apart from avoiding infection, there is no proven prevention or treatment for long COVID. We will perform a randomized placebo-controlled clinical trial to assess whether treatment with the novel antiviral, nirmatrelvir and ritonavir (Paxlovid®) for acute COVID-19 can prevent the development of long COVID.

METHODS: This is a randomized double-blinded placebo-controlled trial that aims to recruit 2000 nonpregnant persons aged 18 to 64 years with acute COVID-19 with positive PCR and/or antigen test and symptom duration of not more than 5 days. Participants will be randomized 1:1 to a 5-day course of Paxlovid (two tablets 150-mg nirmatrelvir and one tablet 100-mg ritonavir twice daily) or a 5-day course of placebo (similar number of tablets of equal appearance). The primary endpoint will be persistent symptoms compatible with long COVID, assessed as the prevalence of a dichotomous variable corresponding to the presence (1) or absence (0) of one or more of the following symptoms: (i) fatigue, (ii) dyspnea, and (iii) cognitive symptoms (memory and/or concentration problems). The primary outcome will be evaluated at 3-month follow-up and then re-evaluated at 6, 12, and 24 months.

DISCUSSION: As more than 750 million people with confirmed COVID-19 have survived globally, the potential burden of long COVID on societies is formidable. If a simple 5-day oral treatment course with nirmatrelvir/ritonavir is shown to prevent long COVID, it would be a highly attractive intervention at an individual level and a mitigation of its public health consequences.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05852873. Registered on May 2023.},
}

Humans
*Ritonavir/administration & dosage/therapeutic use/adverse effects
Adult
Double-Blind Method
*COVID-19 Drug Treatment
*COVID-19/prevention & control/complications
*Antiviral Agents/administration & dosage/therapeutic use/adverse effects
Middle Aged
Young Adult
Adolescent
Male
Randomized Controlled Trials as Topic
SARS-CoV-2
Female
Drug Combinations
Treatment Outcome
Post-Acute COVID-19 Syndrome

@article {pmid41197399,
year = {2025},
author = {Mohanty, MC and Jawade, KS and Rane, SS and Dravid, A and Gurav, YK and Bhardwaj, SD and Borse, R and Bargaje, MD and Sawardekar, V and Gupta, TM and Varose, SY and Patil, AP and Redewad, N and Bandare, G and More, S and Bhor, VM and Doke, P and Abraham, P},
title = {Persistence of post-acute COVID-19 sequelae up to four years in patients with long COVID from Western India: A cross-sectional descriptive study.},
journal = {Journal of infection and public health},
volume = {19},
number = {1},
pages = {103028},
doi = {10.1016/j.jiph.2025.103028},
pmid = {41197399},
issn = {1876-035X},
abstract = {BACKGROUND: Post-Acute Sequelae of COVID-19 or Long COVID (LC) affects millions globally, with persistent immune, neurological, and cardiovascular symptoms posing challenges to healthcare. This study analyses clinical, demographic, and lifestyle differences between LC and recovered (RC) individuals residing in Western India, extending observations up to four years post-infection.

METHODS: A cross-sectional study was conducted in four urban setting tertiary-care hospitals of Western India. Individuals aged 19-70 with documented SARS-CoV-2 infection and persistent or fluctuating symptoms beyond four weeks, unexplained by other diagnoses were recruited in LC group. Recovered individuals with confirmed past infection, negative SARS-CoV-2 RT-PCR at the time of enrolment, and no lingering symptoms were recruited in RC group. The demographic, socio-economic, and clinical data were collected.

RESULTS: Severe acute COVID-19 patients were more frequent in the LC group (n = 104) compared to the RC group (n = 83), though both LC and RC had similar proportions of mild/moderate acute COVID-19 patients. Fatigue was the most persistent symptom (79.80 %), followed by cough and anxiety. Respiratory, cardiovascular, neuro-psychiatric symptoms declined over time, while dermatological, ENT, gastrointestinal, and muscular symptoms fluctuated. LC patients predominantly had hypertension as comorbidity, lower SPO2, and higher pulse rates (p < 0.0001). Rates of hospitalization for COVID-19 treatment were similar, but mechanical ventilation use was exclusively observed in LC patients (10.6 %). Sedentary lifestyles were more frequent in LC (17.30 %) vs. RC (6.02 %, p = 0.0248).

CONCLUSION: Our study is one of the few in Indian population showing occurrence of multiple LC symptoms after 3-4 years of infection. We report severity of COVID-19, use of Remdesivir and mechanical ventilation to be associated with increased odds of LC. Fatigue, cough and anxiety were the most common symptoms reported by LC participants. Our findings establish a much-needed baseline for understanding symptom progression in LC patients, emphasizing the need for targeted interventions and long-term monitoring.},
}

@article {pmid41196899,
year = {2025},
author = {Malambo, W and Sampa-Kawana, M and Chanda, D and Fwoloshi, S and Kaonga, P},
title = {Parametric survival analysis of long COVID among hospitalized patients in Zambia: A retrospective cohort study on the time to symptoms resolving.},
journal = {PLOS global public health},
volume = {5},
number = {11},
pages = {e0004679},
pmid = {41196899},
issn = {2767-3375},
abstract = {Long COVID refers to the continuation or emergence of new symptoms within three months after acute SARS-CoV-2 infection, lasting for at least two months. Although several studies have described COVID-19 sequelae, gaps remain in understanding the temporal dynamics of symptoms resolution - information crucial for patients management and recovery planning. This study evaluated the resolution of COVID-19-related symptoms over time and associated factors among hospitalized patients in Zambia. We conducted a retrospective cohort study among individuals discharged after COVID-19 hospitalization and attending follow-up care in 13 specialized clinics in Zambia from August-2020 to December-2022. Severe acute COVID-19 was defined as hospitalization requiring supplemental oxygen, ICU admission, and/or treatment with steroids/remdesivir. Time-to-symptoms resolution (i.e., survival time) and changes in underlying hazard rate were our primary and secondary outcomes, respectively. We estimated incidence rates, median survival time (onset-to-resolution), and factors associated with symptom resolution using survival analysis, including hazard ratios (HRs) and changes in the underlying hazard rate over time. Among 823 participants, 616 (84.3%) had severe acute COVID-19 illness; 50.6% were female, and median age was 54 years (IQR: 43-64). Overall, 597 (72.5%) had symptoms resolution at a median 51 person-days (IQR: 34-104). Most participants (59.4%) had baseline comorbidities, and 16.6% had received ≥1 COVID-19 vaccine dose. Symptoms resolved at a rate of 12.2 per 1,000 person-days. Severe acute COVID-19 was associated with slower symptom resolution (adjusted HR: 0.68, 95% CI: 0.50-0.92), while infection during the Omicron-predominant period compared to wild-type was associated with faster resolution (aHR: 2.71; 95% CI: 1.46-5.03). The hazard rate peaked around person-day 20 and declined thereafter, indicating a non-monotonic recovery pattern. COVID-19 symptoms resolved more rapidly during the first month of post-acute infection. Patients with persistent symptoms not resolved within this period may experience prolonged recovery, underscoring the need for targeted follow-up and supportive care.},
}

@article {pmid41196059,
year = {2025},
author = {Powers, JM and Leist, SR and Suryadevara, N and Zost, SJ and Binshtein, E and Abdelgadir, A and Mallory, ML and Edwards, CE and Gully, KL and Hubbard, ML and Zweigart, MR and Bailey, AB and Sheahan, TP and Crowe, JE and Montgomery, SA and Harkema, JR and Baric, RS},
title = {Mouse-adapted SARS-CoV-2 Omicron BA.5 infection induces post-acute lung fibrosis in BALB/c mice.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0140625},
doi = {10.1128/jvi.01406-25},
pmid = {41196059},
issn = {1098-5514},
abstract = {UNLABELLED: Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1, subsequent Omicron sub-lineages have continued to emerge, challenging the development of intervention and prevention strategies, including monoclonal antibodies and vaccines. To better understand the pathogenic effects caused by Omicron BA.5 infection, we developed a mouse-adapted virus with overt disease burden in BALB/c mice. Acute disease was characterized by significant weight loss and lung dysfunction following high-dose challenges. In survivor animals that were followed through 107 days post-infection, subpleural fibrosis with associated tertiary lymphoid structures was noted. Serum from these mice demonstrated potent neutralization against BA.5, with substantially reduced neutralization titers against early epidemic, zoonotic, and more recent contemporary XBB.1.5 variants. Intervention with pre-clinical monoclonal antibodies revealed that robust protection from BA.5-induced lung disease was possible after prophylactic administration. Together, this model enables the investigation of therapeutic approaches for both acute and post-acute sequelae of COVID-19.

IMPORTANCE: To best combat the evolving landscape of SARS-CoV-2 variants of interest and variants of concern, the development of effective small animal models is of critical importance. Herein, we describe the development of a model system in BALB/c mice to study the effects of SARS-CoV-2 BA.5 S gene in both acute and chronic disease manifestations. Intriguingly, we determined that fibrotic lung disease with tertiary lymphoid structures was a prominent feature in the lungs of mice that survived through the acute phase of infection. This is a prominent concern in human patients that survive the initial infection insult. As such, and most critically, the model system presented here provides researchers with an effective pathway in which long COVID manifestations and potential interventions can be studied.},
}

@article {pmid41194817,
year = {2025},
author = {Dimitrakopoulou, A and Sarantaki, A and Nanou, CI and Georgakopoulou, VE and Taskou, C and Chouli, M and Diamanti, A},
title = {Long COVID-Related Fatigue During Pregnancy: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e93877},
pmid = {41194817},
issn = {2168-8184},
abstract = {Long sequelae of COVID-19 (Long COVID), or post-acute sequelae of SARS-CoV-2 infection, encompasses a wide range of persistent symptoms, with fatigue emerging as one of the most prevalent and disabling. Pregnant individuals may be uniquely susceptible to post-viral fatigue due to immunological and physiological adaptations during gestation. This review consolidates existing data regarding the prevalence, risk factors, and clinical implications of Long COVID-associated fatigue in pregnant individuals. A narrative review was conducted of studies examining fatigue among pregnant individuals with confirmed SARS-CoV-2 infection. Key outcomes included fatigue prevalence, symptom persistence, associated risk or protective factors, and comparisons with non-pregnant populations. Across both the acute and post-acute stages of COVID-19, fatigue emerged as a consistently common symptom. Its prevalence and persistence varied significantly across studies, partly due to heterogeneity in assessment tools and follow-up durations. Severe acute illness, hospitalization, obesity, and smoking during pregnancy were linked to a higher risk of prolonged fatigue, whereas anosmia appeared to act as a potential protective factor. In contrast, comorbidities such as hypertension, diabetes, and lung disease were not significantly linked to fatigue risk. No consistent associations were found with maternal age or alcohol use. Long COVID-related fatigue presents a substantial burden in pregnancy, with implications for maternal health, quality of life, and postpartum recovery. Early recognition, individualized care strategies, and public health interventions targeting modifiable risk factors are essential to support this vulnerable population. Ongoing research is essential to uncover underlying mechanisms and guide evidence-based clinical management.},
}

@article {pmid41193216,
year = {2025},
author = {Atter, MJ and Hall, P and Evans, RA and Norrie, J and Cohen, J and Williams, B and Chaudhuri, N and Bajwah, S and Higginson, I and Pearson, M and Currow, D and Stewart, G and Fallon, M and Johnson, M},
title = {Morphine for chronic breathlessness (MABEL) in the UK: a health economic evaluation of a multisite, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e102124},
pmid = {41193216},
issn = {2044-6055},
mesh = {Humans ; *Morphine/economics/administration & dosage/therapeutic use ; Cost-Benefit Analysis ; *Dyspnea/drug therapy/economics ; Double-Blind Method ; Male ; Female ; Aged ; Quality-Adjusted Life Years ; Chronic Disease ; United Kingdom ; *Analgesics, Opioid/economics/administration & dosage/therapeutic use ; Middle Aged ; Aged, 80 and over ; },
abstract = {OBJECTIVES: To compare costs and health consequences and to assess the cost-effectiveness of using low-dose oral long-acting morphine in people with chronic breathlessness.

DESIGN: Within-trial planned cost-consequences and cost-effectiveness analysis of data from a multisite, parallel-group, double-blind, randomised, placebo-controlled trial of low-dose, long-acting morphine.

SETTING: 11 hospital outpatients across the UK.

PARTICIPANTS: Consenting adults with chronic breathlessness due to long-term cardiorespiratory conditions.

INTERVENTION: 5-10 mg two times a day oral long-acting morphine with a blinded laxative for 56 days.

PRIMARY OUTCOME MEASURES: Mean and SD of healthcare resource use (HRU) by trial arm; mean differences and 95% CI of costs between trial arms.

SECONDARY OUTCOME MEASURES: Mean differences in 28- and 56-day quality-adjusted life years (QALYs based on EuroQol five-dimension five-level score), Short Form-six dimensional scores and ICEpop CAPability-Supportive Care Measure scores; cost-utility of long-acting morphine for chronic breathlessness.

RESULTS: 143 participants (75 morphine and 67 placebo) were randomised; 140 (90% power, males 66%, mean age 70.5 (SD 9.4)) formed the modified intention-to-treat population (participants receiving at least one dose of study medication). There were more inpatient and fewer outpatient services used by the morphine group versus the placebo. In the base-case analysis at 56 days, long-acting morphine was associated with similar mean per-patient costs and QALYs. There was an increase of £24 (95% CI -£395 to £552) and 0.002 (95% CI -0.004 to 0.008) QALYs. Hospitalisations were the main driver of cost differences. The corresponding incremental cost-effectiveness ratio was £12 000/QALY, with a probability of cost-effectiveness of 54% at a £20 000 willingness-to-pay threshold. In the scenario analysis that excluded costs of adverse events considered unrelated to long-acting morphine by site investigators and researchers, the probability of cost-effectiveness increased to 73%.

CONCLUSION: Oral morphine for chronic breathlessness is likely to be a cost-effective intervention provided adverse events are minimised, but the effect on outcome is small and cautious interpretation is warranted.

TRIAL REGISTRATION NUMBER: ISRCTN87329095.},
}

Humans
*Morphine/economics/administration & dosage/therapeutic use
Cost-Benefit Analysis
*Dyspnea/drug therapy/economics
Double-Blind Method
Male
Female
Aged
Quality-Adjusted Life Years
Chronic Disease
United Kingdom
*Analgesics, Opioid/economics/administration & dosage/therapeutic use
Middle Aged
Aged, 80 and over

@article {pmid41192910,
year = {2025},
author = {Kobayashi, D and Ishikawa, K and Shibutani, K and Jinta, T and Otani, N and Mori, N},
title = {Deterioration of the Swallowing Function Among Patients with COVID-19: A Propensity Score-Matched Cohort Study.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6038-25},
pmid = {41192910},
issn = {1349-7235},
abstract = {Objective This study aimed to investigate whether the swallowing function deteriorates more significantly following coronavirus disease (COVID-19) infection in comparison to other viral respiratory infections in patients with mild to moderate (grade 2) COVID-19. Methods We conducted a propensity score-matched cohort study at St. Luke's International Hospital in Tokyo, Japan, from January 2010 to March 2024. Elderly patients (≥70 years) admitted for viral respiratory infections, including influenza and COVID-19, were included. Patients with suspected bacterial infections, patients who were incapable of oral intake at admission (including those with enteral nutrition and gastrostomy), and patients who died during hospitalization were excluded. The primary outcome was deterioration in the swallowing function, defined as downgrade in food texture category from admission to discharge. Results During the study period, 505 COVID-19 patients and 242 patients with other viral infections were admitted. The mean age was 81.7 years (±7.6) and 401 patients (53.7%) were male. Patients with COVID-19 showed a significantly higher rate of swallowing deterioration in comparison to patients with other viral infections (44.7% vs. 36.6%, p=0.04). Specifically, among patients who consumed a full diet at admission, those with COVID-19 had a higher rate of swallowing deterioration than those with other viral infections (41.9% vs. 31.7%, p<0.01). Conclusion COVID-19 was associated with a significant higher rate of downgrade in the food texture category in comparison to other viral respiratory infections, suggesting a potential impairment in the swallowing function. Given that this deterioration may contribute to prolonged hospitalization in COVID-19 patients, early intervention aimed at restoring and supporting swallowing function is warranted.},
}

@article {pmid41191586,
year = {2025},
author = {Rhodes, S and Douglas, C},
title = {Experiences of accessing primary care by those living with long Covid in New Zealand: A qualitative analysis.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0324489},
pmid = {41191586},
issn = {1932-6203},
mesh = {Humans ; New Zealand/epidemiology ; *COVID-19/epidemiology/therapy ; *Primary Health Care ; Female ; Male ; Middle Aged ; Qualitative Research ; Adult ; *Health Services Accessibility ; Aged ; SARS-CoV-2/isolation & purification ; },
abstract = {BACKGROUND: Long Covid is the persistence of symptoms beyond 12 weeks following acute Covid-19 infection. It is estimated to affect one in ten people and can be extremely debilitating. With few publicly funded long Covid clinics, most people rely on primary care providers as a first point of contact. There is currently limited understanding of the experience of accessing primary health care by adults living with long Covid in New Zealand.

PURPOSE: To explore the experiences of accessing primary health care by adults living with long Covid.

METHODS: A narrative inquiry approach was used to capture participants lived experiences of accessing primary health care. Zoom interviews and discussions were conducted with study participants. The automatically generated transcripts were reviewed and corrected, and the collated data were analysed using Braun and Clarke's thematic analysis.

RESULTS: Eighteen people participated in the interviews. Codes were identified and, through an iterative process, themes were generated, reviewed, and named. The seven themes included lack of upskilling of primary care staff; let down by the Government; self-advocacy and its cost; and throwing money at it.

CONCLUSION(S): The picture painted by participants was bleak with a sense that the world had moved on from Covid-19 and left them behind, with some experiencing a lack of support in primary health care. Reducing the likely long-term health and economic burden of long Covid requires targeted investment and action by Government at every level, along with better utilisation of the allied health workforce in primary care.},
}

Humans
New Zealand/epidemiology
*COVID-19/epidemiology/therapy
*Primary Health Care
Female
Male
Middle Aged
Qualitative Research
Adult
*Health Services Accessibility
Aged
SARS-CoV-2/isolation & purification

@article {pmid41191177,
year = {2025},
author = {Hajek, A and Blome, C and Yon, DK and Soysal, P and Gyasi, RM and Peltzer, K and Pengpid, S and König, HH},
title = {Long COVID and psychosocial factors among middle-aged and older adults. Results of the nationally representative German Ageing Survey.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {313},
pmid = {41191177},
issn = {1720-8319},
mesh = {Humans ; Male ; Female ; Aged ; *COVID-19/psychology/epidemiology ; Germany/epidemiology ; Middle Aged ; *Social Isolation/psychology ; Loneliness/psychology ; Aged, 80 and over ; *Depression/epidemiology/psychology ; *Aging/psychology ; Adult ; SARS-CoV-2 ; Personal Satisfaction ; Surveys and Questionnaires ; Sex Factors ; },
abstract = {BACKGROUND: In addition to the physical symptoms, long COVID can cause considerable psychological burden.

AIMS: To investigate the association of long COVID with depressive symptoms, loneliness, perceived social isolation and life satisfaction (also stratified by sex).

METHODS: Data from the most recent eighth wave of the nationally representative German Ageing Survey was used, encompassing community-dwelling individuals 43 years to 90 years, n = 4,017 individuals in the analytic sample). Psychometrically sound tools were used to quantify the outcomes. Physician-diagnosed long COVID was used as independent variable. Adjusted (weighted) linear regressions with cluster-robust standard errors were used. Robustness checks were conducted.

RESULTS: Regressions adjusted for sociodemographic and lifestyle-related covariates showed that individuals with long COVID had consistently worse psychosocial outcomes compared to individuals without long COVID. However, after additionally adjusting for health-related covariates, only the association between long COVID and perceived social isolation remained significant (β = 0.29, p < 0.001). Stratified by sex, long COVID was significantly associated with higher social isolation scores among women (β = 0.37, p < 0.001), but not among men in the fully adjusted models.

DISCUSSION: Even after adjusting for a wide array of covariates, findings suggest that (female) individuals with long COVID have stronger feelings of not belonging to the society (compared to individuals without long COVID).

CONCLUSIONS: It may be beneficial to find ways to help such individuals feel included in society.},
}

Humans
Male
Female
Aged
*COVID-19/psychology/epidemiology
Germany/epidemiology
Middle Aged
*Social Isolation/psychology
Loneliness/psychology
Aged, 80 and over
*Depression/epidemiology/psychology
*Aging/psychology
Adult
SARS-CoV-2
Personal Satisfaction
Surveys and Questionnaires
Sex Factors

@article {pmid41190342,
year = {2024},
author = {Osati, EFO and Nagu, TJ and Sangeda, RZ and Shayo, GA},
title = {Residual cardiopulmonary manifestations following COVID-19: a Tanzanian ambispective study.},
journal = {BMJ public health},
volume = {2},
number = {Suppl 1},
pages = {e002082},
pmid = {41190342},
issn = {2753-4294},
abstract = {INTRODUCTION: Residual COVID-19 sequelae create a public health concern as they add to the already heavy burden of non-communicable diseases. We set out to investigate the magnitude of residual cardiopulmonary manifestations postacute COVID-19 and their associated factors in Tanzania.

METHODS: This was an ambispective study conducted between 26 March 2021 and 30 July 2021, among 712 hospitalised adults confirmed with SARS-CoV-2 in five tertiary-level hospitals in Tanzania. Retrospective data were analysed to determine baseline characteristics of the patients during acute COVID-19 admission. This was linked to prospective data that were collected 2 years postacute hospitalisation with COVID-19 to determine cardiopulmonary complications among these patients. Radiological pulmonary abnormalities were assessed by contrasted CT scan. Lung function tests were measured using a spirometer. Pulmonary hypertension and heart failure were confirmed by a transthoracic echocardiography. Generalised estimating equations were used to assess the associations between sociodemographic factors, clinical characteristics, treatment modalities and residual cardiopulmonary sequelae.

RESULTS: About half 317/712 (44.5%) were diagnosed with residual cardiopulmonary complications. Approximately 54% of participants were male. Median age (IQR) was 60 (48-69) years. Cardiopulmonary sequelae were significantly associated with body mass index (BMI) ≥25.0 kg/m[2] compared with those with BMI <25.0 kg/m[2] (adjusted OR (aOR) (95% CI)=3.4 (2.47 to 4.84), p<0.001), smokers compared with non-smokers (aOR (95% CI)=2.39 (1.09 to 5.23), p=0.030] and among participants who did not receive steroids during the acute COVID-19 (aOR (95% CI)= 1.62(1.16 to 1.92), p=0.042].

CONCLUSION: The independent predictors of residual cardiopulmonary manifestations due to COVID-19 were overweight, cigarette smoking, hypoxia and non-use of steroids during the acute phase of COVID-19 disease. Public health interventions addressing weight reduction and smoking cessation in conjunction with steroid use in acute COVID-19 may largely reduce the incidence of cardiopulmonary long COVID-19.},
}

@article {pmid41189723,
year = {2025},
author = {Fineberg, D and Moreau, A and Schneider-Futschik, EK and Armstrong, CW},
title = {A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID.},
journal = {ACS pharmacology & translational science},
volume = {8},
number = {10},
pages = {3411-3431},
pmid = {41189723},
issn = {2575-9108},
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID (LC) are increasingly recognized as debilitating postinfectious conditions that impact both individuals and society. Recent research highlights the potential of metformin, an antidiabetic agent, as a treatment for these syndromes by targeting their underlying mechanisms. This review assesses the effectiveness of metformin in ME/CFS and LC, which involve complex dysfunctions related to cytokines, glycolysis, ATP generation, oxidative stress, gastrointestinal microbiomes, and vascular endothelial function. Metformin, traditionally known for its antihyperglycemic properties may offer broader therapeutic benefits by influencing these pathological pathways. It works by inhibiting complexes I and IV of the electron transport chain, which reduces the strain on malfunctioning complex V and decreases the production of harmful free radicals. Additionally, metformin's impact on mTOR signaling could improve energy metabolism in ME/CFS and LC by downregulating an overactive but underperforming protein, thereby alleviating symptoms. Beyond the impact on cellular metabolism, metformin has shown to have anti-inflammatory, vascular, gastrointestinal, neuroprotective and epigenetic effects. We explore this impact of metformin and the potential role it could play to help people with ME/CFS. While metformin shows promise, it is unlikely to be a stand-alone solution. Instead, it may be part of a broader treatment strategy that includes other therapies targeting neurocognitive and autonomic impairments.},
}

@article {pmid41187495,
year = {2025},
author = {Demir Unal, E},
title = {A Neuroimmunological Axis between systemic autoimmunity and Parkinson's disease following long-COVID: A case series.},
journal = {Journal of neuroimmunology},
volume = {410},
number = {},
pages = {578795},
doi = {10.1016/j.jneuroim.2025.578795},
pmid = {41187495},
issn = {1872-8421},
abstract = {BACKGROUND: Long COVID, a multisystemic syndrome following SARS-CoV-2 infection characterized by persistent immune dysregulation, systemic inflammation, and neuroimmune dysfunction, is a significant area of investigation in the neurological sciences. The hypothesis that this pathophysiological state can trigger de novo autoimmune diseases and potentially accelerate underlying neurodegenerative processes is gaining traction. This case series aims to illuminate the potential neuroimmunological link between these conditions by presenting the patients who developed de novo Crohn's disease (CD) and ankylosing spondylitis (AS) following Long COVID and were subsequently diagnosed with post-COVID Parkinson's Disease (PD).

CASE PRESENTATIONS: The first case is a 50-year-old female who developed de novo CD six months after COVID-19 pneumonia, managed with the TNF-α inhibitor. Eighteen months later, she presented with parkinsonian motor deficits. The post-COVID PD diagnosis was supported by susceptibility-weighted MRI showing loss of nigrosome-1 and DAT-SPECT revealing a presynaptic dopaminergic deficit. The second case is a 48-year-old female who was diagnosed with de novo AS eight months post-COVID, treated with adalimumab. Twenty-six months later, she developed progressive bradykinesia and rigidity. Neuroimaging confirmed post-COVID PD with corresponding loss of nigrosome-1 and a presynaptic dopaminergic deficit on DAT-SPECT. In both genetically negative cases, dopaminergic therapy led to substantial motor improvement, with Unified Parkinson's Disease Rating Scale (UPDRS) Part IIIscores decreasing from 8 to 3 and 14 to 4, respectively.

CONCLUSION: This case series proposes a pathogenic cascade wherein SARS-CoV-2 infection acts as an environmental trigger, initiating a Long COVID-associated immune dysregulation that first precipitates a systemic autoimmune disorder. We hypothesize that this sustained inflammatory milieu subsequently accelerates the dysfunction of the dopaminergic system in predisposed individuals, thereby unmasking the clinical phenotype of post-COVID PD. This novel association highlights a potential nexus between virally-induced autoimmunity and subsequent neurodegeneration, offering a new perspective in the field of neuroimmunology.},
}

@article {pmid41186895,
year = {2025},
author = {Dihan, QA and Alshammari, N and Elhusseiny, AM and Rickels, KL and Shakarchi, AF and Chauhan, MZ and Sallam, AB},
title = {Long COVID and the development of new-onset uveitis: a large database study.},
journal = {Journal of ophthalmic inflammation and infection},
volume = {15},
number = {1},
pages = {79},
pmid = {41186895},
issn = {1869-5760},
abstract = {PURPOSE: To determine the impact of long COVID diagnosis on the risk of developing uveitis among individuals vaccinated and not vaccinated against COVID.

METHODS: We conducted a population-based retrospective cohort study using an aggregate healthcare database, TriNetX, which includes data from over 127 million patients across 95 international healthcare organizations. Four cohorts were compared: (1) Unvaccinated, Long COVID; (2) Unvaccinated, No Long COVID; (3) Vaccinated, Long COVID; and (4) Vaccinated, No Long COVID. Patients with any history of uveitis prior to initial COVID diagnosis were excluded. The primary outcome was the risk of new-onset uveitis at 1 and 2 years following the diagnosis of long COVID.

RESULTS: Unvaccinated, long COVID patients demonstrated an increased risk of developing new-onset uveitis compared to unvaccinated, no long COVID controls at 1 year (aHR: 2.01, 95% CI: 1.19-3.38) and 2 years (aHR: 1.60, 95% CI: 1.08-2.37). The highest risk was seen for anterior uveitis at 1 year (aHR: 1.96, 95% CI: 1.13-3.41) and 2 years (aHR: 1.59, 95% CI: 1.06-2.40). Other uveitis subtypes did not show an increased risk in this cohort. Among vaccinated individuals, there was not increased risk in those with long COVID compared to those without at 1 year (aHR: 0.95, 95% CI: 0.58-1.55) and 2 years (aHR: 0.97, 95% CI: 0.65-1.46).

CONCLUSION: Unvaccinated individuals with long COVID have an increased risk of developing new uveitis, particularly anterior uveitis. Vaccinated individuals with long COVID did not have an increased risk of developing uveitis compared to vaccinated non-long COVID individuals.},
}

@article {pmid41184874,
year = {2025},
author = {Laursen, CH and Nielsen, TB and Leth, S and Schiøttz-Christensen, B and Nielsen, CV and Langagergaard, V and Sørensen, L and Sørensen, D and Oestergaard, LG},
title = {Characterising disability in patients with long COVID-does gender matter? an analytic cross-sectional study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3744},
pmid = {41184874},
issn = {1471-2458},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Middle Aged ; *Activities of Daily Living ; Sick Leave/statistics & numerical data ; Adult ; Sex Factors ; *Persons with Disabilities/statistics & numerical data ; Denmark/epidemiology ; Employment/statistics & numerical data ; Aged ; },
abstract = {BACKGROUND: Long COVID affects patients' daily functioning and activity participation. However, gender-specific differences remain insufficiently explored despite well-documented effects of gender on health outcomes. This study examines gender differences in sociodemographic characteristics, employment status, sick leave, and mental fatigue among individuals with long COVID. Furthermore, this study explores self-reported and prioritised problems with activities of daily living (ADL) across genders and compares patterns between women and men. We hypothesised that traditional gender roles would manifest in distinct challenges for women and men.

METHODS: We included 780 individuals (567 women and 213 men) diagnosed with long COVID who were referred to occupational therapy at a Danish outpatient clinic for long COVID. Sociodemographic characteristics, employment status, and sick leave were self-reported. Mental fatigue was assessed using the Mental Fatigue Scale, and ADL problems using the Canadian Occupational Performance Measure. A qualitative deductive content analysis was conducted to further categorise prioritised ADL problems.

RESULTS: A higher proportion of women than men had higher education (55% vs. 37%). No statistically significant gender difference was seen in the prevalence of sick leave (57% vs. 50%). Moderate to severe mental fatigue was reported by 78% of women and 68% of men, with women reporting significantly higher fatigue (p < 0.001). Minor gender differences in ADL problems were observed, with more women reporting difficulties in household management, quiet recreation, and social interaction. Both women and men prioritised similar ADL problems, such as paid work, physical activity, social interaction, and fulfilling caregiving roles.

CONCLUSION: ADL challenges reported by women and men were largely similar and had a significant impact on their daily lives. Identifying key activity limitations is essential to inform effective rehabilitation strategies.},
}

Humans
Male
Female
Cross-Sectional Studies
*COVID-19/epidemiology
Middle Aged
*Activities of Daily Living
Sick Leave/statistics & numerical data
Adult
Sex Factors
*Persons with Disabilities/statistics & numerical data
Denmark/epidemiology
Employment/statistics & numerical data
Aged

@article {pmid41183079,
year = {2025},
author = {Konishi, K and Yamamoto, S and Sada, RM and Asano, K and Onozuka, D and Tanaka, S and Miyazawa, S and Kinoshita, M and Kutsuna, S},
title = {Research to evaluate safety and impact of long COVID intervention with Ensitrelvir for National Cohort (RESILIENCE Study): A protocol for a randomized, double-blind, placebo-controlled trial.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0335609},
pmid = {41183079},
issn = {1932-6203},
mesh = {Humans ; Japan/epidemiology ; Double-Blind Method ; *COVID-19/virology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Randomized Controlled Trials as Topic ; Registries ; Cohort Studies ; Indazoles ; Triazines ; Triazoles ; },
abstract = {This study was registered with the Japan Registry of Clinical Trials on February 16, 2024 (jRCTs051230184, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs051230184).},
}

Humans
Japan/epidemiology
Double-Blind Method
*COVID-19/virology
SARS-CoV-2
*COVID-19 Drug Treatment
Randomized Controlled Trials as Topic
Registries
Cohort Studies
Indazoles
Triazines
Triazoles

@article {pmid41182495,
year = {2025},
author = {Pini, L and Guerini, M and Giordani, J and Levi, G and Latronico, N and Piva, S and Peli, E and Benoni, R and Pini, A and Zucchi, G and Piras, S and El Masri, Y and Visca, D and Caminati, M and Senna, G and De Ciuceis, C and Rosei, CA and Muiesan, ML and Tantucci, C},
title = {24-Month assessment of respiratory function in patients hospitalized for severe SARS-CoV-2 pneumonia: a follow-up study.},
journal = {Internal and emergency medicine},
volume = {},
number = {},
pages = {},
pmid = {41182495},
issn = {1970-9366},
abstract = {Long COVID affects multiple body systems, with the respiratory system being particularly vulnerable. This study aimed to analyze the lung ventilatory function and diffusion capacity of patients with severe SARS-CoV-2 pneumonia during a 24-month follow-up course. Ventilatory function and lung diffusion capacity were assessed 6, 12, 18, and 24 months after hospital discharge. Ventilatory parameters, Diffusion Lung Carbon Monoxide (DLCO), and KCO (Carbon Monoxide transfer coefficient) normalization were defined as achieving values > 80% predicted. A total of 222 patients admitted to the Intensive Care Unit (ICU) at ASST Spedali Civili di Brescia, Brescia, Italy, were enrolled. Among the 172 patients who completed the study, 140 (63%) achieved normalization of ventilatory parameters, DLCO, and KCO. The median time to recovery was 4.5 months, and the hazard ratio (HR) decreased by 2% for each year of age increase. The median time to normalize ventilatory parameters (VC, FVC, FEV1, FEV1/FVC, TLC, and KCO) was 1.5 months, while the median time to alveolar volume (VA) normalization was 4.5 months. Male gender reduces the odds of normalization for FEV1/FVC and VA. The median time to DLCO normalization was 9 months, with HR reduced by 3.1% as each year of age increased and augmented by 226% in obese subjects. 24 months after severe COVID pneumonia, 14% of patients had persistent ventilatory and/or diffusive defects. Our study documented that male sex, age, and obesity impact the odds of normalization of ventilatory function and diffusive capacity. These findings underline the chronic nature of lung damage following severe COVID-19 pneumonia and the need for long-term follow-ups.},
}

@article {pmid41181095,
year = {2025},
author = {Simón-Rueda, A and Sánchez-Menéndez, C and Casado, G and Fuertes, D and Murciano-Antón, MA and Mateos, E and Domínguez-Mateos, S and Pozo, F and García-Pérez, J and Pérez-Olmeda, M and Cervero, M and Massanella, M and Moncunill, G and Torres, M and Coiras, M},
title = {Immune dysregulation and endothelial dysfunction associate with a pro-thrombotic profile in Long COVID.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1613195},
pmid = {41181095},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications/blood/virology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Biomarkers/blood ; Aged ; Adult ; *Thrombosis/immunology ; Cohort Studies ; *Endothelium, Vascular/immunology ; Antibodies, Viral/blood ; Blood Coagulation ; },
abstract = {INTRODUCTION: Long COVID (LC) affects approximately 10% of individuals post-SARS-CoV-2 infection, with symptoms persisting beyond 12 weeks. The underlying mechanisms remain unclear, and current models often focus on pre-existing comorbidities.

METHODS: This cohort study aimed to identify robust biomarkers and clarify LC pathogenesis through a comprehensive analysis performed in 32 LC individuals 26 months post-infection compared with 35 fully recovered individuals recruited between March and July 2022. Blood and fecal samples were collected, and multiple parameters associated with immune dysfunction, endothelial damage, bacterial translocation, and coagulation alterations, alongside signs of viral persistence and sociodemographic and clinical features, were analyzed.

RESULTS: Although viral RNA was undetected on blood or stool, elevated plasma IgG against the nucleocapsid may indicate frequent reinfections, greater infection severity, or delayed immune normalization. Increased levels of prothrombin, thrombin, fibrinogen, sEPCR, and CRP pointed to persistent endothelial dysfunction and coagulation imbalance. Lower levels of the bactericidal protein REG3A suggest potential disruptions in mucosal immune response. We found no major differences in traditional comorbidities, highlighting that LC may stem from distinct pathogenic mechanisms beyond pre-existing conditions. Importantly, our study revealed impaired humoral immunity and identified an association between vaccine heterogeneity and increased LC risk, emphasizing the relevance of consistent vaccination strategies. A Random Forest model using the measured biomarkers achieved 100% accuracy in classifying LC individuals, reinforcing their diagnostic potential.

DISCUSSION: These findings support a multifactorial model of LC involving immune dysregulation and persistent endothelial damage that led to coagulation abnormalities and a pro-thrombotic profile, supporting that LC is more closely related to a sustained, uncontrolled inflammatory response rather than immunodeficiency, and underscoring the value of multidimensional biomarker profiling for guiding clinical management and prevention strategies.},
}

Humans
*COVID-19/immunology/complications/blood/virology
Male
Female
Middle Aged
*SARS-CoV-2/immunology
Biomarkers/blood
Aged
Adult
*Thrombosis/immunology
Cohort Studies
*Endothelium, Vascular/immunology
Antibodies, Viral/blood
Blood Coagulation

@article {pmid41179091,
year = {2025},
author = {Tadisina, S and Mohammed, S and Asad, R and Tselovalnikova, T and Nguyen, B and Akella, PV and Abu Kishk, M},
title = {Prevalence and Evolution of Thyroid Dysfunction in COVID-19: A Retrospective Study.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93542},
pmid = {41179091},
issn = {2168-8184},
abstract = {Objective Coronavirus-19 (COVID-19) is known to mainly affect the respiratory system, but it has also been found to impact multiple endocrine systems. Various studies have shown a relationship between thyroid dysfunction and COVID-19 infection. However, there is controversy around thyroid-inflammatory autoimmune conditions contributing to a worse prognosis of COVID-19 infection. The main objective of our single-center retrospective study is to evaluate the prevalence and evolution of thyroid dysfunction in patients with COVID-19 infection. Methods A total of 615 adults with confirmed COVID-19 infection, between March 2020 and December 2023, who had thyroid function tests (TFTs), were included in the study. Patients with pre-existing thyroid disease or on medications affecting thyroid function were excluded. Thyroid dysfunction was defined as any abnormality in TFTs. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 26 (Released 2018; IBM Corp., Armonk, NY, USA). Differences in continuous variables were assessed using independent sample t-tests, and Pearson's Chi-square tests were used to compare categorical variables. Results The study showed that 84 patients (13.6%) had thyroid dysfunction. The most common abnormalities were non-thyroidal illness syndrome (NTIS, n = 39; 46.4%) and subclinical hypothyroidism (n = 37; 44%), followed by overt hyperthyroidism (n = 6; 7.1%) and overt hypothyroidism (n = 2; 2.3%). The evolution of thyroid dysfunction was followed for about one year by chart review and showed no progression to overt thyroid dysfunction. Conclusion We noted that thyroid dysfunction is not uncommon in patients with COVID-19, with subclinical hypothyroidism and NTIS being the most prevalent findings. These abnormalities are often transient and resolve without progression in most cases. The pathogenesis appears to involve both direct viral effects and systemic inflammatory responses. Given the potential overlap between thyroid dysfunction and long COVID symptoms, selective monitoring of thyroid function is warranted in symptomatic individuals.},
}

@article {pmid41178423,
year = {2025},
author = {Limami, Y and Wahnou, H and Ndayambaje, M and Hba, S and Chgari, O and Ammara, M and El Kebbaj, R and Naya, A and Oudghiri, M and Duval, RE},
title = {SARS-CoV-2: A Liver Brief.},
journal = {WIREs mechanisms of disease},
volume = {17},
number = {6},
pages = {e70005},
doi = {10.1002/wsbm.70005},
pmid = {41178423},
issn = {2692-9368},
mesh = {Humans ; *COVID-19/complications/virology/pathology/immunology ; *SARS-CoV-2/pathogenicity ; *Liver Diseases/virology/pathology ; *Liver/virology/pathology/immunology/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Virus Internalization ; },
abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has revealed the virus's ability to induce multi-organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID-19 patients are explored, focusing on direct viral infection, immune-mediated damage, and the gut-liver axis. SARS-CoV-2 enters liver cells through the Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre-existing liver conditions, such as metabolic-associated fatty liver disease (MAFLD), alcohol-related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID-19 patients. Post-COVID-19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug-Induced Liver Injury (DILI) from COVID-19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS-CoV-2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver-related complications in both acute and Long COVID-19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.},
}

Humans
*COVID-19/complications/virology/pathology/immunology
*SARS-CoV-2/pathogenicity
*Liver Diseases/virology/pathology
*Liver/virology/pathology/immunology/metabolism
Angiotensin-Converting Enzyme 2/metabolism
Virus Internalization

@article {pmid41177912,
year = {2025},
author = {Rhidenour, KB and Thompson, CM and Babu, S and Kelpinski, LF},
title = {"Everything Looks Normal": Patient Narratives of Contested Legitimacy in Long COVID Medical Encounters.},
journal = {Health communication},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/10410236.2025.2580322},
pmid = {41177912},
issn = {1532-7027},
abstract = {This study examines how individuals with long COVID navigate illness experiences when faced with normal test results. Through qualitative analysis of 1,043 posts from r/covidlonghaulers between July 2020 and January 2021, we identified four key themes: overlapping diagnostic possibilities increase confusion, discordance in treatment plans, sustained uncertainty, and challenges to credibility. Our findings reveal how polysemic meanings of normal become sites of tension between biomedical evidence and lived experiences, creating a communicative burden for patients who must advocate for legitimacy and care. The analysis demonstrates how overlapping symptomology with other conditions complicates diagnosis, while patients develop strategies to navigate dismissive healthcare encounters and establish credibility when symptoms persist despite normal results. Reddit served as a vital platform for patients to exchange communication strategies for healthcare encounters and find validation when test results invalidated their experiences. A strength of this study is its ability to capture the experience of people with long COVID at the community's inception through a platform that connected them despite geographical barriers. Our findings provide valuable insights into how patients navigate contested illness experiences and offer concrete pathways for enhancing patient-provider communication around medically unexplained symptoms across various diagnoses.},
}

@article {pmid41176968,
year = {2025},
author = {Thaweethai, T and Gross, RS and Pant, DB and Rhee, KE and Jernigan, TL and Kleinman, LC and Snowden, JN and Salisbury, AL and Kinser, PA and Milner, JD and Tantisira, K and Warburton, D and Mohandas, S and Wood, JC and Fitzgerald, ML and Carmilani, M and Krishnamoorthy, A and Reeder, HT and Foulkes, AS and Stockwell, MS and , },
title = {Preventive effect of vaccination on long COVID in adolescents with SARS-CoV-2 infection.},
journal = {Vaccine},
volume = {68},
number = {},
pages = {127907},
doi = {10.1016/j.vaccine.2025.127907},
pmid = {41176968},
issn = {1873-2518},
abstract = {PURPOSE: In adolescents (12-17 years), it is unknown whether COVID-19 vaccination reduces progression from COVID-19 to Long COVID (LC) beyond preventing SARS-CoV-2 infection. We assessed the effect of vaccination among SARS-CoV-2 infected adolescents.

METHODS AND RESULTS: Participants were recruited from over 60 US healthcare and community settings. The exposure was any COVID-19 vaccination 6 months prior to infection. The outcome was LC defined using the LC research index. Vaccinated (n = 724) and unvaccinated (n = 507) adolescents were matched on sex, infection date, and enrollment date. The risk of LC was 36 % lower (95 % CI, 17 %, 50 %) in vaccinated compared to unvaccinated participants.

CONCLUSIONS: Vaccination reduces the risk of LC. Given the profound impact LC can have on the health and well-being of adolescents and the limited availability of treatments during this developmental stage, this supports vaccination as a strategy for preventing LC by demonstrating an important secondary prevention effect.},
}

@article {pmid41176305,
year = {2025},
author = {Palacio, A and Bast, E and Phillip, P and Milanes, I and Klimas, N and Tamariz, L},
title = {Virtual Group Clinics Improve Self-Reported Long COVID Symptoms Among Veterans: Results From a Holistic Care Approach.},
journal = {Journal of the American Medical Directors Association},
volume = {27},
number = {1},
pages = {105963},
doi = {10.1016/j.jamda.2025.105963},
pmid = {41176305},
issn = {1538-9375},
}