@article {pmid41605350,
year = {2026},
author = {Gerhards, SK and Luppa, M and Zülke, A and Sander, C and Schomerus, G and Buechner, R and Wirkner, K and Reusche, M and Zeynalova, S and Lehmann, J and Baber, R and Obrig, H and Herzig, S and Thöne-Otto, A and Witte, AV and Villringer, A and Fricke, C and Bergh, FT and Saur, D and Schroeter, ML and Löffler, M and Engel, C and Riedel-Heller, SG},
title = {Depressive and anxiety symptoms in individuals with Long-COVID: Does social network matter? - Results of a German Long-COVID study.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121272},
doi = {10.1016/j.jad.2026.121272},
pmid = {41605350},
issn = {1573-2517},
abstract = {BACKGROUND: Some patients previously infected with SARS-CoV-2 develop symptoms that are summarized under the term Long COVID (LC). There is limited evidence on how social characteristics influence depressive and anxiety symptoms in adults with LC.

METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). Anxiety symptoms were measured using the Generalized Anxiety Disorder Scale (GAD-7). The living situation (alone vs. with someone) was assessed by a single question. The social network was assessed using the Lubben Social Network Scale (LSNS). Multivariate regression analysis was performed.

RESULTS: In n = 410 participants with LC from Leipzig, Germany (mean age = 47.12, SD = 12.24), we found that living with others was associated with fewer depressive symptoms compared to living alone (B = -2.18, p = .011). A larger social network was associated with fewer anxiety symptoms in adults with LC symptoms (IRR = 0.99, p = .008).

CONCLUSION: Social factors, such as social network and living situation, are associated with mental health factors like depressive and anxiety symptoms in adults with LC. Further research is required in order to elucidate the complex interplay between social factors and mental health in people with LC in the context of longitudinal studies. Future research directions are discussed.},
}

@article {pmid41603315,
year = {2026},
author = {Petry Moecke, DM and Kwong, EH and Cressman, S and Yao, J and Singh, C and Taylor, C and Camp, PG},
title = {Rehabilitation needs of long COVID patients in British Columbia.},
journal = {PM & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70092},
pmid = {41603315},
issn = {1934-1563},
support = {//Ministry of Health, British Columbia/ ; //British Columbia Lung Foundation/ ; //UBC Post-COVID Interdisciplinary Clinical Care Network with St. Paul's Foundation/ ; },
abstract = {INTRODUCTION: COVID-19 can result in persistent symptoms and functional impairment that significantly impact daily functioning, highlighting the need for targeted rehabilitation. However, there is a lack of data on what proportion of long COVID patients need rehabilitation and which types are required.

OBJECTIVE: To estimate the rehabilitation needs of patients with long COVID.

DESIGN: Retrospective, cross-sectional analysis of clinical data.

SETTING: Post-COVID recovery clinic in British Columbia, Canada.

PARTICIPANTS: Individuals with long COVID, defined as having symptoms persisting beyond 3 months post infection, with the first clinic visit occurring within 6 months post infection.

INTERVENTION: Not applicable.

MAIN OUTCOME MEASURES: We created thresholds based on objective tests and patient-reported outcomes to determine rehabilitation needs.

RESULTS: Data from 3709 patients who visited the clinic between March 2020 and May 2023 were available for analysis; 33% met the study eligibility criteria (n = 1237). Patients were primarily women (65%) and white (57%), with a mean age of 49 ± 14 years. Two thirds had required hospitalization. The average time from infection to clinic visit was 136 ± 34 days. At 3-6 months post infection, the most common COVID-19 symptoms were fatigue, dyspnea, muscle weakness, and muscle/joint aches. Most patients exceeded the rehabilitation threshold for dyspnea (83%), fatigue (78%), frailty (74%), and posttraumatic stress disorder (58%). Quality of life was impaired for 80%. Neuropsychological symptoms like anxiety (42%) and depression (36%) were also prevalent. Reductions in 6-minute walk distance (≥25%) and sit-to-stand performance (≥50%) occurred in 26% and 55% of patients, respectively. The majority of participants (98%) exceeded at least one test threshold for rehabilitation, and most (85%) were eligible for more than one type. The most required types of rehabilitation were pulmonary rehabilitation (83%), mental health support (78%), and neurorehabilitation (70%).

CONCLUSION: The need for rehabilitation services among individuals experiencing long COVID in British Columbia is substantial. Use of predefined thresholds that incorporate measures of both symptom burden and functional impairment can effectively support the identification of high-need patients and their overall rehabilitation needs. Combined with clinicians' expertise, this approach can facilitate timely, evidence-based referrals to specialized care for those who need it.},
}

@article {pmid41602330,
year = {2025},
author = {Arroyo-Romero, S and Gómez-Sánchez, L and Suárez-Moreno, N and Navarro-Cáceres, A and Domínguez-Martín, A and Lugones-Sánchez, C and González-Sánchez, S and Sánchez-Moreno, A and Rodríguez-Sánchez, E and García-Ortiz, L and Navarro-Matias, E and Gómez-Marcos, MA},
title = {Association between cardiovascular, psychotropic and anti-inflammatory/analgesic drug use and vascular dysfunction in individuals with long COVID. BioICOPER study.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1691153},
pmid = {41602330},
issn = {2297-055X},
abstract = {INTRODUCTION: While the deterioration in the general health of patients with long COVID (LC) is well documented, no studies have assessed changes in medication use and their relationships with vascular health. This study aimed to evaluate the increase in the use of various drug classes in LC and its relationship with vascular structure and function.

METHODS: Each participant in the sample of 305 subjects diagnosed with LC completed a questionnaire on medication use, verified in medical records. Pre-pandemic and current drug use were recorded. Arterial stiffness was measured with the VaSera device, which estimates the cardio-ankle vascular index and brachial-ankle pulse wave velocity (ba-PWV); carotid-femoral pulse wave velocity was determined using the Sphygmocor device. Vascular structure was assessed by carotid intima-media thickness (c-IMT), measured with a Sonosite Micromax ultrasound. This analysis focuses exclusively on macrovascular parameters. Statistical analyses were performed with SPSS software.

RESULTS: Use of all classes of medication increased. Patients with a greater rise in drug use after an LC diagnosis showed higher vascular parameters. Greater cardiovascular drug use was positively associated with ba-PWV, an indicator of arterial stiffness (β = 0.301, 95%CI: 0.024-0.577). Increased anti-inflammatory/analgesic drug use was positively associated with c-IMT, a marker of vascular wall thickness (β = 0.012, 95%CI: 0.001-0.023).

CONCLUSIONS: Medication use rose from 2019 to the time of inclusion in the study. The increase in cardiovascular and anti-inflammatory/analgesic drug use was positively associated with ba-PWV and c-IMT, respectively, suggesting a link between greater drug use and impaired vascular health in LC.},
}

@article {pmid41601165,
year = {2026},
author = {Amato, C and Iovino, P and Spinicci, M and Longobucco, Y and Livi, L and Giovannoni, L and Guidotti, C and Pietrini, L and Braschi, F and De Filippis, C and Ermini, L and Gori, L and Zocchi, C and Argirò, A and Bartoloni, A and Olivotto, I and Lavorini, F and Marchionni, N and Fattirolli, F and Rasero, L},
title = {Factors associated with persistent symptoms after COVID-19 infection: a longitudinal study on an Italian cohort of patients discharged from hospital.},
journal = {Infectious diseases (London, England)},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/23744235.2026.2620811},
pmid = {41601165},
issn = {2374-4243},
abstract = {BACKGROUND: Although the acute phase of the COVID-19 pandemic has subsided, long COVID remains a significant and ongoing public health concern. Persistent symptoms continue to affect a substantial proportion of COVID-19 survivors, increasing healthcare burden.

OBJECTIVE: This study aims to identify the determinants of long-term symptom trajectories following COVID-19 infection.

METHODS: We conducted a prospective cohort study of 1666 adults discharged after hospitalisation for COVID-19 in Tuscany, Italy. The presence of mental confusion, exertional dyspnoea, fatigue, and insomnia was assessed at 1, 3, 6, 9, and 12 months post-discharge. The mean hospital stay was 13.6 (±12) days and 131 patients required intensive care unit admissions. Latent growth curve models were used to examine the baseline prevalence and longitudinal trajectories of each symptom, and to identify demographic and clinical factors associated with symptom persistence.

RESULTS: Fatigue was the most common persistent symptom at baseline, followed by exertional dyspnoea, insomnia, and mental confusion. Female sex was consistently associated with both baseline presence and persistence of all symptoms. Older age was linked to baseline mental confusion and to persistent dyspnoea and fatigue. Markers of greater acute severity (ICU admission, longer hospital stay, higher WHO score) were associated with symptom improvement over time. Pre-existing coronary heart disease and cancer independently predicted persistent dyspnoea and fatigue, whereas hypertension appeared protective.

CONCLUSIONS: Persistent symptoms are common after COVID-19 and vary by sex, age, comorbidities, and acute disease features. Symptoms may persist up to 12 months post-hospitalisation, underscoring the need for long-term follow-up and targeted interventions.},
}

@article {pmid41600912,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Saldanha-Araujo, F and Argañaraz, GA and Argañaraz, ER},
title = {Correction: de Melo et al. SARS-CoV-2 Spike Protein and Long COVID-Part 1: Impact of Spike Protein in Pathophysiological Mechanisms of Long COVID Syndrome. Viruses 2025, 17, 617.},
journal = {Viruses},
volume = {18},
number = {1},
pages = {},
doi = {10.3390/v18010002},
pmid = {41600912},
issn = {1999-4915},
abstract = {Error in Funding [...].},
}

@article {pmid41600911,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER},
title = {Correction: de Melo et al. SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome. Viruses 2025, 17, 619.},
journal = {Viruses},
volume = {18},
number = {1},
pages = {},
doi = {10.3390/v18010003},
pmid = {41600911},
issn = {1999-4915},
abstract = {In the original publication [...].},
}

@article {pmid41599072,
year = {2026},
author = {Dave, RS and Fox, HS},
title = {Synergy of SARS-CoV-2 and HIV-1 Infections in the Human Brain.},
journal = {Pathogens (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/pathogens15010089},
pmid = {41599072},
issn = {2076-0817},
mesh = {Humans ; *COVID-19/virology/pathology/complications/epidemiology ; *HIV Infections/virology/pathology/complications ; *SARS-CoV-2 ; *HIV-1 ; *Brain/virology/pathology ; Microglia/virology/pathology ; Coinfection/virology ; Cytokines/metabolism ; },
abstract = {This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes.},
}

Humans
*COVID-19/virology/pathology/complications/epidemiology
*HIV Infections/virology/pathology/complications
*SARS-CoV-2
*HIV-1
*Brain/virology/pathology
Microglia/virology/pathology
Coinfection/virology
Cytokines/metabolism

@article {pmid41598609,
year = {2026},
author = {Balan, OV and Malysheva, IE and Tikhonovich, EL and Lysenko, LA},
title = {Dysregulation of MMP-2 and MMP-9 in Post-COVID-19 and IPF: Correlations with Systemic Inflammation and Endothelial Dysfunction.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/jcm15020671},
pmid = {41598609},
issn = {2077-0383},
abstract = {Background/Objectives: Post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF) exhibit significant clinical and pathophysiological overlap, suggesting convergent molecular pathways driving fibrosis. This prospective longitudinal study investigates the sustained dysregulation of matrix metalloproteinases (MMP)-2 and MMP-9 and its relationship with evolving systemic inflammation and endothelial dysfunction in convalescent COVID-19 patients, with comparative analysis to IPF. Methods: We conducted a prospective observational study of 86 patients at 6 and 12 months post-SARS-CoV-2 infection, stratified by high-resolution CT evidence of PCPF (FB+ group, n = 32) or absence of fibrosis (FB- group, n = 54). Gene expression of MMP-2 and MMP-9 in peripheral blood leukocytes and circulating levels of MMP-2, MMP-9, pro-inflammatory cytokines (TNF-α, IL-6), and endothelial dysfunction markers (Endothelin-1 [ET-1], adhesion molecules) were quantified via qRT-PCR and ELISA. A pre-pandemic healthy control group (HD, n = 20) and an IPF patient group (n = 10) served as comparators. Results: A significant, sustained elevation of MMP-2 and MMP-9 was observed in all post-COVID-19 patients versus HDs, most pronounced in the FB+ group and qualitatively similar to IPF. A critical divergence emerged: FB- patients showed resolution of systemic inflammation (reduced TNF-α, IL-6), whereas FB+ patients exhibited persistent cytokine elevation. Critically, a delayed, severe endothelial dysfunction, characterized by a profound surge in ET-1 and elevated adhesion molecules, manifested exclusively in the FB+ cohort at 12 months. Positive correlations linked plasma MMP-2/9 levels with ET-1 (rs = 0.65, p = 0.004; rs = 0.49, p = 0.009) and ET-1 with sICAM-1 (rs = 0.68, p = 0.01). Conclusions: The development of PCPF is associated with a distinct pathogenic triad: sustained MMP dysregulation, failure to resolve inflammation, and severe late-phase endothelial dysfunction. The correlative links between these components suggest a self-reinforcing loop. This systemic signature mirrors patterns in IPF, underscoring shared final pathways in fibrotic lung disease and identifying the MMP-inflammation-endothelial axis as a promising target for biomarker development and therapeutic intervention.},
}

@article {pmid41598473,
year = {2026},
author = {Goicoechea-Calvo, A and Navarro Expósito, N and Coll-Fernández, R and Colomer Giralt, M and Martín Saavedra, A and González-Aumatell, A and Méndez-Hernández, M and Carreras-Abad, C and Moreira, M and Giralt-López, M and Pallarès, N and Tebe Cordomi, C and Rodríguez-Palmero, A and Rodrigo, C and Mata, MJD},
title = {Impact of Pulmonary Rehabilitation on Physical, Mental Health and Quality of Life in Children with Post-COVID-19 Condition: A 12-Month Quasi-Experimental Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/jcm15020535},
pmid = {41598473},
issn = {2077-0383},
abstract = {Background/Objectives: Evidence on pulmonary rehabilitation (PR) in paediatric post-COVID-19 condition (PPCC) is scarce. This study aimed to evaluate the association of a PR programme with changes in physical and mental health and quality of life in PPCC over a 12-month follow-up. Methods: A quasi-experimental pre-post single-arm study was conducted, with no control group, in PPCC patients attending an outpatient PR unit. The primary outcome was change in exercise capacity (6 min walk test, 6MWT). Secondary outcomes included inspiratory and peripheral muscle strength, quadriceps muscle morphology by ultrasound, fatigue, physical activity, quality of life, and psychiatric symptoms, assessed using validated paediatric instruments. Results: A total of 115 PPCC patients (mean age 13.3 years; 66.1% female) completed the PR. 6MWD distance increased from 509 ± 87 to 546 ± 86 (+37 m; p < 0.001; D: 0.50). Handgrip strength increased by 2.4 kg, maximal inspiratory pressure increased by 15 cmH2O, physical activity increased by 2.4 points, fatigue score improved by 9.3 points, and quality of life improved by 11 points (all p < 0.001). Rectus femoris thickness increased by 0.56 mm (p = 0.005), psychiatric symptom scores decreased by 4.5 points (p < 0.001), and rectus femoris echo-intensity decreased (p = 0.003). Conclusions: Multidisciplinary PR appears feasible and potentially effective in improving physical function, psychological well-being, and quality of life in PPCC, supporting the need for evidence-based paediatric rehabilitation.},
}

@article {pmid41597495,
year = {2026},
author = {Jiménez-Antona, C and Moreta-Fuentes, R and Varillas-Delgado, D and Moreta-Fuentes, C and Laguarta-Val, S},
title = {From Exhaustion to Empowerment: A Pilot Study on Motor Control-Based Exercise for Fatigue and Quality of Life in Long COVID-19 Patients.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {1},
pages = {},
doi = {10.3390/medicina62010210},
pmid = {41597495},
issn = {1648-9144},
mesh = {Humans ; Female ; Pilot Projects ; *Quality of Life/psychology ; *COVID-19/complications/psychology/rehabilitation ; *Fatigue/therapy/etiology/rehabilitation ; Middle Aged ; *Exercise Therapy/methods ; Adult ; SARS-CoV-2 ; Aged ; },
abstract = {Background and Objectives: Long COVID-19 (LC) is a multifaceted condition characterized by persistent fatigue and impaired health-related quality of life (HRQoL). Exercise intolerance and post-exertional symptom exacerbation (PESE) pose challenges for rehabilitation. This study aimed to evaluate the effects of a 12-week core-focused plank exercise program on fatigue and HRQoL in women with LC, using validated patient-reported measures. Materials and Methods: A pilot quasi-experimental design was implemented, with non-randomized group allocation. Thirty-nine women with LC were recruited from the Madrid Long COVID Association. Participants were assigned to either an intervention group (n = 20), which completed a supervised plank-based motor control program, or a control group (n = 19), which maintained usual activity. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS), and HRQoL was measured using the EQ-5D-5L and EQ Visual Analog Scale (EQ-VAS). Body composition was evaluated via bioelectrical impedance analysis. Results: The intervention group showed significant reductions after intervention in the MFIS total scores compared to the control group, particularly in the physical (21.26 ± 6.76 vs. 25.21 ± 6.06; p < 0.001) and psychosocial domains (4.51 ± 0.41 vs. 5.21 ± 0.38; p < 0.001), without triggering PESE. EQ-VAS scores improved significantly (63.94 ± 15.33 vs. 46.31 ± 14.74; p = 0.034). No significant changes were found in body composition parameters, suggesting that benefits were driven by neuromuscular adaptations rather than morphological changes. Conclusions: A core-focused, non-aerobic exercise program effectively reduced fatigue and improved perceived health status in women with LC. These findings support the use of motor control-based interventions as a safe and feasible strategy for LC rehabilitation, particularly in populations vulnerable to PESE, suggesting clinical applicability for the rehabilitation of women with LC. Further randomized trials are warranted to confirm these results and explore long-term outcomes.},
}

Humans
Female
Pilot Projects
*Quality of Life/psychology
*COVID-19/complications/psychology/rehabilitation
*Fatigue/therapy/etiology/rehabilitation
Middle Aged
*Exercise Therapy/methods
Adult
SARS-CoV-2
Aged

@article {pmid41597249,
year = {2026},
author = {Stigliano, E and Tocci, A and Florio, R and Arena, V and Amadoro, G},
title = {Olfactory Dysfunction and Cognitive Deterioration in Long COVID: Pathomechanisms and Clinical Implications in Development of Alzheimer's Disease.},
journal = {Cells},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/cells15020176},
pmid = {41597249},
issn = {2073-4409},
support = {RF-2021-12374//Italian Ministry of Health/ ; 971925//Alzheimer's Association Research Grant/ ; FOE D.M865/2019//Fondo Ordinario Enti/ ; },
mesh = {Humans ; *COVID-19/complications/pathology ; *Alzheimer Disease/etiology/pathology ; *Olfaction Disorders/etiology ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; Anosmia ; },
abstract = {Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer's Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection.},
}

Humans
*COVID-19/complications/pathology
*Alzheimer Disease/etiology/pathology
*Olfaction Disorders/etiology
SARS-CoV-2
*Cognitive Dysfunction/etiology
Anosmia

@article {pmid41596479,
year = {2026},
author = {Otsuka, Y and Soejima, Y and Nakano, Y and Suyama, A and Takase, R and Oguni, K and Masuda, Y and Omura, D and Sakurada, Y and Matsuda, Y and Hasegawa, T and Honda, H and Tokumasu, K and Ueda, K and Otsuka, F},
title = {Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone.},
journal = {International journal of molecular sciences},
volume = {27},
number = {2},
pages = {},
doi = {10.3390/ijms27020832},
pmid = {41596479},
issn = {1422-0067},
support = {2025//Ofuji Endocrine Medical Award/ ; 2025//Growth Science Foundation/ ; 2025//Kobayashi-Magobei Foundation/ ; },
mesh = {Humans ; Female ; *COVID-19/complications/metabolism/physiopathology ; Adult ; *Gonadotropin-Releasing Hormone/metabolism ; Retrospective Studies ; Male ; Middle Aged ; Hydrocortisone/blood ; *Hypothalamic Diseases/metabolism ; *Hypothalamus/metabolism/physiopathology ; Hypothalamo-Hypophyseal System/metabolism/physiopathology ; Thyrotropin-Releasing Hormone/metabolism ; Adrenocorticotropic Hormone/blood ; SARS-CoV-2 ; Corticotropin-Releasing Hormone/metabolism ; },
abstract = {Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic-pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (-0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements.},
}

Humans
Female
*COVID-19/complications/metabolism/physiopathology
Adult
*Gonadotropin-Releasing Hormone/metabolism
Retrospective Studies
Male
Middle Aged
Hydrocortisone/blood
*Hypothalamic Diseases/metabolism
*Hypothalamus/metabolism/physiopathology
Hypothalamo-Hypophyseal System/metabolism/physiopathology
Thyrotropin-Releasing Hormone/metabolism
Adrenocorticotropic Hormone/blood
SARS-CoV-2
Corticotropin-Releasing Hormone/metabolism

@article {pmid41595923,
year = {2026},
author = {Bartholmae, M and Gunawardena, T},
title = {Comparison of Mental Illness Comorbidity Pre-Pandemic vs. Pandemic-Era and Associations with Clinical and Demographic Characteristics for Virginia Public Hospital Inpatient Discharges with a Substance Use Disorder.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {1},
pages = {},
doi = {10.3390/ijerph23010129},
pmid = {41595923},
issn = {1660-4601},
support = {Not available - I moved to a different institution and no longer have access to funds//Hampton Roads Community Foundation/ ; },
mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; *Mental Disorders/epidemiology ; Middle Aged ; Adult ; Hospitals, Public/statistics & numerical data ; Comorbidity ; Retrospective Studies ; Cross-Sectional Studies ; Virginia/epidemiology ; *Substance-Related Disorders/epidemiology ; Adolescent ; Young Adult ; Aged ; Patient Discharge/statistics & numerical data ; SARS-CoV-2 ; Inpatients/statistics & numerical data ; Pandemics ; },
abstract = {The rise in mental illnesses after the COVID-19 pandemic is well documented. However, it is not known whether the rates of mental illness comorbidity increased. The objectives of this study were to compare mental illness comorbidity rates before and after the pandemic among inpatients with SUD and to test associations between mental illness comorbidity, physical illness, and demographics. We used a retrospective cross-sectional design in a sample of inpatient discharges (N = 233,017) at Virginia public hospitals from January 2018 to December 2022. We used Z tests to compare rates of mental illness comorbidity pre- and post-pandemic and Chi-square tests to examine associations of mental illness comorbidity with physical illness and demographics. Single and comorbid mental illness significantly increased from pre- to post-pandemic, p < 0.0001. Mental illness comorbidity was significantly associated with sex, age, race, insurance, COVID-19/Long COVID, HIV/AIDS, COPD, hypertension, obesity, CVD, cancer, and diabetes (p < 0.0001). There was a significant increase in mental illness comorbidity, which was significantly associated with age, race, sex, and physical illnesses. Children/adolescents, females, American Indians, and individuals with HIV/AIDS had the highest rates of mental illness comorbidity. Public health action is needed to address the increase in complex medical needs among people with SUD.},
}

Humans
*COVID-19/epidemiology/psychology
Male
Female
*Mental Disorders/epidemiology
Middle Aged
Adult
Hospitals, Public/statistics & numerical data
Comorbidity
Retrospective Studies
Cross-Sectional Studies
Virginia/epidemiology
*Substance-Related Disorders/epidemiology
Adolescent
Young Adult
Aged
Patient Discharge/statistics & numerical data
SARS-CoV-2
Inpatients/statistics & numerical data
Pandemics

@article {pmid41595843,
year = {2025},
author = {Dhaouadi, S and Bouguerra, H and Hechaichi, A and Letaief, H and Safer, M and Aichouch, C and Zouayti, A and Bougatef, M and Neffati, A and El Mili, N and Mhadhbi, R and Bouafif Ép Ben Alaya, N},
title = {Long-Term Health Effects of COVID-19 in Tunisia, 2020-2021.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {1},
pages = {},
doi = {10.3390/ijerph23010049},
pmid = {41595843},
issn = {1660-4601},
mesh = {Humans ; Tunisia/epidemiology ; *COVID-19/epidemiology/complications ; Female ; Male ; Adult ; Middle Aged ; Cross-Sectional Studies ; Aged ; Prevalence ; Young Adult ; Adolescent ; SARS-CoV-2 ; Child ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; },
abstract = {Background: Some patients suffer from persistent symptoms following a COVID-19 infection, referred to as long COVID. The aims of the study were to estimate the prevalence of long COVID and study its determinants in Tunisia. Methods: We conducted a nationwide cross-sectional study among a representative sample of COVID-19 survivors residing in Tunisia between June and August 2022. We selected a random sample, stratified by age and region, among residents registered in the national surveillance database with a SARS-CoV-2 positive test taken from September 2020 to September 2021 (n = 479,743). The expected sample size was 384. We defined a patient with long COVID as having at least one self-reported symptom persisting for more than four weeks after the first confirmation of SARS-CoV-2 infection (RT-PCR or Ag-RDT) and not explained by an alternative diagnosis. Trained healthcare workers interviewed consenting respondents by phone using a structured questionnaire. We described continuous variables using median and interquartile range (IQR). We measured the prevalence of long COVID and its 95% confidence interval (95% CI). We estimated the association between explanatory variables (socio-demographic, lifestyle and comorbidities, SARS-CoV-2 history infection, COVID-19 vaccination status) and long COVID using a log-binomial model, reporting adjusted prevalence ratios (a-PR) and its 95% CI. Results: Of 1094 persons contacted, 416 were enrolled (response rate: 38%). Long-COVID prevalence was 64% (267/416); 95% CI [59-69%]. The sex ratio (M:F) was 0.72. Age ranged from 1 to 101 years, with a median of 41 years (IQR:31-55 years). The most common symptoms were fatigue (63%), myalgia/arthralgia (33%), and cognitive symptoms (52%). Median duration of long-COVID symptoms was 11 months (IQR: 3-14 months). In multivariate analysis, experiencing acute COVID-19 (a-PR = 1.5; 95% CI [1.0-2.1]), being a woman of childbearing age (a-PR = 1.2; 95% CI [1.0-1.4]) and residing in the central region (a-PR = 1.5; 95% CI [1.1-2.0]) were significantly associated with a higher prevalence of long COVID. Conclusions: Long COVID is prevalent in Tunisia affecting patients with multiple symptoms initially, those residing in the central region and young women. We recommend to enhance healthcare access and medical follow-up both during and after the infection, focusing on identified risk groups. We also recommend to conduct further research to optimize management of long-COVID patients.},
}

Humans
Tunisia/epidemiology
*COVID-19/epidemiology/complications
Female
Male
Adult
Middle Aged
Cross-Sectional Studies
Aged
Prevalence
Young Adult
Adolescent
SARS-CoV-2
Child
Aged, 80 and over
Post-Acute COVID-19 Syndrome

@article {pmid41595726,
year = {2026},
author = {Arroyo-Romero, S and Gomez-Sanchez, L and Suarez-Moreno, N and Navarro-Caceres, A and Dominguez-Martin, A and Lugones-Sanchez, C and Gonzalez-Sanchez, S and Gomez-Sanchez, M and Rodriguez-Sanchez, E and Garcia-Ortiz, L and Navarro-Matias, E and Gomez-Marcos, MA},
title = {Clinical Manifestations of Subjects with Long COVID and Their Associations with Drug Use: The BioICOPER Study.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/biomedicines14010192},
pmid = {41595726},
issn = {2227-9059},
support = {PI21/00454//Instituto de Salud Carlos III/ ; RD21/0016/0010//Network for Research on Chronicity, Primary Care, and Health Promotion/ ; GRS 2501/B/22//Junta de Castilla y León/ ; CB22/06/00035//Centro de Investigación Biomédica en Red/ ; },
abstract = {Background/Objectives: Long COVID (LC) is associated with more than 200 symptoms. This study aimed to evaluate the correlation between symptoms clusters and pharmacological treatment in patients with LC and to explore differences by sex. Methods: We conducted a cross-sectional descriptive study including 304 participants diagnosed with LC according to the World Health Organization criteria. Symptoms during the acute phase, at the time of diagnosis of LC, and those persisting across both phases were collected by anamnesis. Symptoms were grouped into six clusters: systemic, neurocognitive, respiratory/cardiovascular, musculoskeletal, neurological/neuromuscular, and psychological/psychiatric. Drug use was assessed through a questionnaire verified by the medical records, including the consumption of cardiovascular drugs, antidepressants/anxiolytics, and anti-inflammatory/analgesics. Results: Patients reported a mean of 5.23 ± 1.10 symptoms in the acute phase, 4.20 ± 1.70 at LC diagnosis, and 3.83 ± 1.80 persisting across both phases. The most consumed pharmacological group was cardiovascular drugs (43.3%), followed by antidepressants/anxiolytics (34.8%). Psychotropic drugs and anti-inflammatory/analgesic drugs showed a positive association with all symptomatic groups (p < 0.05). Cardiovascular drugs showed a positive association with cardiorespiratory (β = 0.19, p < 0.05), neuromuscular (β = 0.11, p < 0.05), and psychological (β = 0.14, p < 0.05) symptoms. Conclusions: Psychotropic and anti-inflammatory/analgesic drugs were positively associated with all symptom clusters, while cardiovascular drugs were associated only with cardiorespiratory, neuromuscular, and psychological symptoms, highlighting the relevance of better characterization of treatment patterns in this population.},
}

@article {pmid41595678,
year = {2026},
author = {Daodu, LP and Raste, Y and Allgrove, JE and Arrigoni, FIF and Kayyali, R},
title = {A Retrospective Observational Study of Pulmonary Impairments in Long COVID Patients.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/biomedicines14010145},
pmid = {41595678},
issn = {2227-9059},
support = {KU-RCP10656/"Long COVID -Croydon//Croydon Health Services NHS Trust/ ; },
abstract = {Background/Objective: Pulmonary impairments have been identified as some of the most complex and debilitating post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID. This study identified and characterised the specific forms of pulmonary impairments detected using pulmonary function tests (PFT), chest X-rays (CXR), and computed tomography (CT) scans in patients with long COVID symptoms. Methods: We conducted a single-centre retrospective study to evaluate 60 patients with long COVID who underwent PFT, CXR, and CT scans. Pulmonary function in long COVID patients was assessed using defined thresholds for key test parameters, enabling categorisation into normal, restrictive, obstructive, and mixed lung-function patterns. We applied exact binomial (Clopper-Pearson) 95% confidence intervals to calculate the proportions of patients falling below the defined thresholds. We also assessed the relationships among spirometric indices, lung volumes, and diffusion capacity (DLCO) using scatter plots and corresponding linear regressions. The findings from the CXRs and CT scans were categorised, and their prevalence was calculated. Results: A total of 60 patients with long COVID symptoms (mean age 60 ± 13 years; 57% female) were evaluated. The cohort was ethnically diverse and predominantly non-smokers, with a mean BMI of 32.4 ± 6.3 kg/m[2]. PFT revealed that most patients had preserved spirometry, with mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) above 90% predicted. However, a significant proportion exhibited reductions in lung volumes, with total lung capacity (TLC) decreasing in 35%, and diffusion capacity (DLCO/TLCO) decreasing in 75%. Lung function pattern analysis showed 88% of patients had normal function, while 12% displayed a restrictive pattern; no obstructive or mixed patterns were observed. Radiographic assessment revealed that 58% of chest X-rays were normal, whereas CT scans showed ground-glass opacities (GGO) in 65% of patients and fibrotic changes in 55%, along with findings such as atelectasis, air trapping, and bronchial wall thickening. Conclusions: Spirometry alone is insufficient to detect impairment of gas exchange or underlying histopathological changes in patients with long COVID. Our findings show that, despite normal spirometry results, many patients exhibit significant diffusion impairment, fibrotic alterations, and ground-glass opacities, indicating persistent lung and microvascular damage. These results underscore the importance of comprehensive assessment using multiple diagnostic tools to identify and manage chronic pulmonary dysfunction in long COVID.},
}

@article {pmid41594661,
year = {2026},
author = {Förster, CY and Shityakov, S},
title = {A Possible Role for the Vagus Nerve in Physical and Mental Health.},
journal = {Biomolecules},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/biom16010121},
pmid = {41594661},
issn = {2218-273X},
support = {Fo-315/5-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Vagus Nerve/physiology/physiopathology ; *Vagus Nerve Stimulation/methods ; *Mental Health ; COVID-19/therapy ; Animals ; SARS-CoV-2 ; Depression/therapy ; },
abstract = {For decades, researchers have explored the therapeutic potential of the vagus nerve through vagus nerve stimulation (VNS). Initially developed for epilepsy, VNS has since been applied to treat resistant depression, stroke recovery, and inflammatory conditions. Transcutaneous VNS (tVNS) now offers a noninvasive alternative, fueling clinical trials in disorders ranging from rheumatoid arthritis and migraines to long COVID-19. Mechanistic studies suggest that afferent and efferent vagal fibers modulate immune responses, mood regulation, and neurotransmitter systems. The SPARC initiative has accelerated mapping of vagal circuits, enabling more precise approaches to stimulation. Despite progress, the results remain mixed: while some patients experience lasting symptom relief, others respond no better than to placebo. Depression studies, in particular, highlight both the promise and the complexity of VNS, as inflammation, motivation circuits, and gut-brain signaling emerge as key modulators. Next-generation closed-loop devices and circuit-specific targeting may improve efficacy and reduce adverse effects. VNS research thus lies at the intersection of neuromodulation, psychiatry, and immunology-offering hope for hard-to-treat conditions, yet demanding rigorous trials to separate myths from medicine. In this article, we review the current clinical and experimental applications of tVNS, analyze its mixed efficacy across psychiatric, immunological, and neurological disorders, and highlight the mechanistic insights, stimulation parameters, and emerging technologies that may shape next-generation therapies.},
}

Humans
*Vagus Nerve/physiology/physiopathology
*Vagus Nerve Stimulation/methods
*Mental Health
COVID-19/therapy
Animals
SARS-CoV-2
Depression/therapy

@article {pmid41593681,
year = {2026},
author = {Feliz, J and Gonçalves, J and Cabedo, C and Brito, J and Gamas, M and Neves, MI and Soares, H},
title = {Long-term sex differences in symptoms and immune profile in long COVID.},
journal = {Biology of sex differences},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13293-026-00825-9},
pmid = {41593681},
issn = {2042-6410},
support = {Grant Agreement No. GA 101159729//European Union's Horizon Europe research and innovation action through the projects MPS_NOVA/ ; Agreement No. GA 101079264//EVCA Grant/ ; LA/P/0087/2020//Research Unit UID/04462: iNOVA4Health and by Associated Laboratory LS4FUTURE/ ; },
abstract = {BACKGROUND: Long COVID (LC) is a post-infectious condition affecting millions worldwide, characterized by persistent multisystem symptoms. Females are disproportionately affected, reporting higher symptom burden, particularly neurocognitive and neurosensory complaints. While short-term immunopathology has been described, the long-term clinical course, immune dysregulation, and sex-specific underpinnings remain poorly understood.

METHODS: We analyzed 34 participants experiencing persisting symptoms from 9 months to 5 years post-SARS-CoV-2 infection, alongside 26 SARS-CoV-2-infected controls without symptoms. Clinical assessments, symptom inventories, comorbidity analysis, and work capacity evaluation were performed. Immune profiling included flow cytometry of CD4⁺ and CD8⁺ T cells, NK cells, and B cells, as well as quantification of plasma cytokines, soluble factors, and cytotoxic molecules, analyzed in a sex-disaggregated manner.

RESULTS: Females with LC exhibited higher symptom burden, particularly persistent fatigue, neurocognitive and neurosensory complaints, which increased with age and tended to increase with disease duration, whereas males showed no clear age- or duration-related patterns. Comorbidities, especially affecting endocrine, metabolic, and circulatory systems, were more frequent in females and aligned with symptom severity. Immune profiling revealed subtle but sex-specific differences: females had reduced CD8⁺ T cell cytotoxic profile, lower NKG2D and granzyme K expression, increased sCD40L and sFAS, and decreased perforin, whereas males displayed elevated TNF-α. NK cell function, B cells, and humoral immunity remained largely intact. Over half of participants reported functional impairments affecting work capacity.

CONCLUSIONS: Even though our cohort is small it suggests that prolonged LC is characterized by sex-specific differences in symptom burden and immune profiles. Reduced cytotoxic CD8⁺ T cell profile in females may contribute to viral persistence and neurological symptoms, whereas elevated inflammatory markers in males suggest distinct immune pathways. These findings highlight the need for sex- and duration-specific management strategies, the identification of biomarkers, and the development of personalized therapies targeting specific LC endotypes.},
}

@article {pmid41592666,
year = {2026},
author = {Ngiam, JN and Wee, LE and Lim, JT and Loy, EX and Koh, MCY and Tay, AT and Lou, HX and Kim, P and Chiew, CJ and Young, BE and Vasoo, S and Lye, DCB and Tan, KB},
title = {Early administration of neutralising monoclonal antibodies and post-acute sequelae of COVID-19.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108435},
doi = {10.1016/j.ijid.2026.108435},
pmid = {41592666},
issn = {1878-3511},
abstract = {OBJECTIVES: Post-acute sequelae of COVID-19 (PASC) are more common in unvaccinated or immunocompromised individuals. In Singapore, neutralising monoclonal antibodies (mAbs) were offered early in the disease course to such high-risk patients. We evaluated the impact of early mAb use on the risk of post-acute multi-system complications and symptoms.

METHODS: Using national COVID-19 registries and healthcare claims data, we conducted a retrospective cohort study including all Singaporeans who were unvaccinated, partially vaccinated, or immunocompromised at the time of SARS-CoV-2 infection between July 2021 and December 2022. Individuals were stratified by receipt of mAbs. Overlap weighting was applied to balance baseline characteristics. Competing risks regression was used to compare outcomes from 31 to 300 days post-infection, adjusted for demographics, vaccination status, and comorbidities.

RESULTS: Of 19,689 eligible hospitalised individuals, 6.9% received early mAb therapy. While mAb treatment had no significant impact on overall post-acute sequelae (aHR for any sequelae:1.26[0.98-1.63]), we observed an increased risk of autoimmune diseases (aHR=2.20[1.22-3.97]), particularly systemic lupus erythematosus and rheumatoid arthritis). There was also elevated risk of deep venous thrombosis (aHR=1.83[1.03-3.22]), but this was no longer significant after adjusting for prior healthcare utilisation.

CONCLUSIONS: Early mAb therapy did not significantly alter overall PASC risk but was associated with increased autoimmune complications. These findings may highlight the need for long-term safety monitoring in future mAb trials for SARS-CoV-2.},
}

@article {pmid41591677,
year = {2026},
author = {Zheng, M},
title = {Large-Scale Disease-Wide Association Study Identified Predisposition Links Between Influenza and Cardiovascular Diseases.},
journal = {Cardiovascular toxicology},
volume = {26},
number = {2},
pages = {20},
pmid = {41591677},
issn = {1559-0259},
support = {32100739//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Influenza, Human/epidemiology/diagnosis ; *Cardiovascular Diseases/epidemiology/diagnosis ; Female ; Male ; Middle Aged ; Comorbidity ; Risk Assessment ; Aged ; Adult ; Time Factors ; Risk Factors ; },
abstract = {BACKGROUND: Influenza remains a major global health threat and, akin to "long COVID," has been linked to prolonged multi-organ comorbidities ("long flu"). Cardiovascular diseases (CVDs) are increasingly recognized in the pathogenesis of influenza, yet most prior work emphasizes acute or short-term outcomes and rarely contrasts multiple endpoints over extended horizons.

METHODS: This study conducted a disease-wide association study (DWAS), assembling individuals with clinically coded influenza without pneumonia (n = 5136) and population comparators (n = 314,673). Using age- and sex-adjusted Cox models, this analysis screened 106 comorbid endpoints classified by ICD-10/ICD-O-3 and FinnGen disease taxonomy. Associations were evaluated bidirectionally-before influenza (predisposition) and after influenza (subsequent risk)-within prespecified 1-, 5-, and 15-year time windows.

RESULTS: Influenza showed broad associations spanning circulatory, nervous, endocrine-metabolic, respiratory, musculoskeletal, and other organ systems. CVD endpoints demonstrated the most persistent and directionally consistent DWAS signals. In pre-influenza analyses, greater baseline cardiovascular burden-including heart failure, coronary atherosclerosis, hypertension, major coronary heart disease, atrial fibrillation/flutter, myocardial infarction, stroke, pulmonary embolism, and venous thromboembolism-was associated with higher susceptibility to subsequent influenza. In post-influenza analyses, elevated risks remained for key CVD outcomes-atrial fibrillation/flutter, heart failure, myocardial infarction, and stroke. Non-cardiovascular endpoints (e.g., migraine, sleep apnoea, spinal stenosis, osteoporosis, chronic obstructive pulmonary disease, diabetic nephropathy, and chronic kidney disease) also showed bidirectional associations with influenza, thereby situating CVD within a broader comorbidity and frailty context of influenza.

CONCLUSIONS: In this population-scale DWAS, CVDs emerged as the most significant comorbidities of influenza. Conceptualizing influenza as a "cardiovascular stress test" supports targeted prevention (e.g., vaccination prioritization) and intensified cardiovascular risk management around influenza seasons. While the biological mechanism remains unclear, this study will motivate future studies integrating biomarkers, cardiovascular imaging, and virologic-immunologic profiling to disentangle causal mechanisms.},
}

Humans
*Influenza, Human/epidemiology/diagnosis
*Cardiovascular Diseases/epidemiology/diagnosis
Female
Male
Middle Aged
Comorbidity
Risk Assessment
Aged
Adult
Time Factors
Risk Factors

@article {pmid41590531,
year = {2026},
author = {Rodrigues, CNDS and Angelotto, FR and Diotto, VL and Cristofoletti, DDM and Araújo, TOP and de Lima, MA and Neto, JC and Prestes, J and Navalta, J and Pereira, GB},
title = {Long COVID Does Not Impair Hemodynamic, Vascular, or Autonomic Responses to Maximal Exercise: Sex-Stratified Study in Young Adults.},
journal = {Journal of personalized medicine},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/jpm16010038},
pmid = {41590531},
issn = {2075-4426},
support = {23112.031858/2024-30//Pós-Graduação em Fisiologia Clínica do Exercício do Departamento de Ciências Fisiológicas da Universidade Federal de São Carlos/ ; },
abstract = {Background/Objectives: Long COVID (LC) has been linked to fatigue, exercise intolerance, and autonomic dysfunction, but sex-stratified data on cardiovascular responses to maximal exercise-an essential component of personalized medicine-are scarce. This study aimed to examine hemodynamic, autonomic, and functional responses during and up to 24 h after a cardiopulmonary exercise test (CPET) in young adults with and without Long COVID (LC). Methods: In this cross-sectional study, we assessed 38 physically active adults, who were allocated into four subgroups stratified by clinical condition (LC or control) and biological sex: control-female (CON-F; n = 10), LC-female (LC-F; n = 10), control-male (CON-M; n = 10), and LC-male (LC-M; n = 8). Outcomes included systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), cardiac output (CO), total (TPR) and peripheral vascular resistance (PVR), pulse wave velocity (PWV), augmentation index (AIx@75), and heart rate variability (HF, LF, LF/HF), assessed at rest, peak effort, recovery (1, 3, 5, 10, 30, and 60 min), and through 24 h ambulatory blood pressure monitoring (ABPM) after CPET. Results: SBP increase appropriately during exercise, with higher peaks in males (p < 0.01), and returned to baseline within 5 min across all groups. HR recovery was preserved; however, LC-F showed lower values than CON-F at 3, 5, and 10 min (126 vs. 144 bpm, p = 0.020; 119 vs. 136 bpm, p = 0.020; 94 vs. 109 bpm, p = 0.011), though all groups normalized by 60 min. PWV, AIx@75, TPR and PVR exhibited expected sex-related patterns without LC-related impairments. HRV indices showed transient post-exercise shifts (HF↓, LF↑, LF/HF↑). Ambulatory monitoring confirmed preserved circadian modulation, with normal systolic dipping (11-13%) and no abnormal nocturnal patterns. Conclusions: Young physically active adults with LC showed preserved hemodynamic, autonomic, and vascular responses during and after maximal exercise. These findings contribute to personalized medicine by showing that individualized, sex-stratified cardiovascular assessments reveal no clinically relevant impairments in this population, supporting tailored clinical decision making and exercise prescription.},
}

@article {pmid41590528,
year = {2026},
author = {Selvi, FR and Longhino, D and Lucca, G and Baglivo, I and Zavarella, MA and Laface, C and Bruno, L and Gamberale, S and Fabbroni, L and Rizzi, A and Aruanno, A and Buonagura, R and Curci, M and Buonomo, A and Viola, M and Ianiro, G and Landi, F and Tosato, M and Gasbarrini, A and Caruso, C},
title = {Investigation of Biomarkers in Allergic Patients with Long COVID.},
journal = {Journal of personalized medicine},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/jpm16010031},
pmid = {41590528},
issn = {2075-4426},
abstract = {Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ[2] = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ[2] = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population.},
}

@article {pmid41589860,
year = {2026},
author = {Al-Delaimy, WK and Bruno, W and Shadyab, A and Saquib N, N and Goveas, JS},
title = {Psychological symptoms predict long coronavirus disease 2019: a prospective analysis from the Women's Health Initiative.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {41589860},
issn = {1530-0374},
abstract = {OBJECTIVE: Those with mental illnesses are likely at higher risk of developing coronavirus disease 2019 (COVID-19), and elderly are disproportionately impacted and as a result suffer more from long COVID. The aim of this analysis was to determine the associations of preexisting depressive and anxiety symptoms with developing COVID-19 positivity, long COVID-19, and compliance with the use of protective measures against contracting COVID-19.

METHODS: A subsample (n = 18,820) of the Women's Health Initiative study cohort completed longitudinal questionnaires on depressive and anxiety symptoms between 1993 and 2021 and reported on COVID-19 testing and compliance-related questions in 2020 and 2021. Logistic regression analyses were used to prospectively determine associations of a history of mental health symptoms with COVID-related outcomes.

RESULTS: Reported history of depressive and anxiety symptoms was not associated with COVID-19 positivity. However, higher anxiety scores were associated with higher odds of long COVID (OR = 1.05 [95% CI: 1.03-1.07]). Women with both depressive and anxiety symptoms versus neither symptom had 78% higher odds of long COVID (OR = 1.78 [95% CI: 1.13-2.81 P = 0.001]). The odds of compliance with COVID-19 mitigation measures was significantly lower among women with previous long-term depressive symptoms (OR = 0.67 [95% CI: 0.55-0.82]), with both long-term depressive and anxiety symptoms (OR = 0.75 (95% CI: 0.61-0.93) P < 0.0001), and with higher long-term perceived stress score (OR = 0.94 [95% CI: 0.92-0.97]). However, a higher short-term anxiety score during early COVID was weakly associated with the higher odds of compliance of prevention mitigation measures (OR = 1.03 [95% CI: 1.02-1.03]).

CONCLUSIONS: Older women with past mental health symptoms may be at higher risk of developing long COVID and having lower compliance with COVID prevention measures.},
}

@article {pmid41588020,
year = {2026},
author = {Abbasi, A and Hansen, N and Palade, J and Paredes, D and Meechoovet, B and Van Keuren-Jensen, K and Pirrotte, P and Stringer, WW},
title = {Serum extracellular vesicle RNA profiles in long COVID: insights from exercise-induced gene modulation.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {3469},
pmid = {41588020},
issn = {2045-2322},
mesh = {Humans ; *Extracellular Vesicles/genetics/metabolism ; *COVID-19/genetics/blood/virology ; Male ; Female ; Middle Aged ; *Exercise/physiology ; SARS-CoV-2/genetics ; Adult ; Pilot Projects ; Gene Expression Regulation ; },
abstract = {The Persistence of SARS-CoV-2 in tissues has been proposed as a driver of prolonged symptoms in long COVID. Pulmonary rehabilitation with exercise training is a well-established intervention for improving symptoms, functional capacity, and inflammation in chronic cardiorespiratory diseases. To investigate whether long COVID is associated with persistent viral or immune-related signals, we analyzed the long RNA profile of circulating extracellular vesicles (EVs) to determine the presence of virus-related transcripts and assess changes in response to exercise training. Fourteen adults with long COVID participated in this single-center pilot clinical trial and completed a 10-week aerobic exercise training program (twenty 1.5 h sessions). Serum-derived EV RNA profiles were analyzed via sequencing at rest (T0) and peak cardiopulmonary exercise testing (T1), before (V2) and after (V24) exercise training. Differentially expressed genes (DEGs) were identified (q < 0.05), and pathway activation analysis was performed. Serum EVs carried diverse RNA species, including protein-coding RNAs, long non-coding RNAs, short non-coding RNAs, and pseudogenes, with no virus-related RNAs detected. No significant DEGs were identified at rest between pre- and post-training, nor in response to acute exercise at pre-training. However, following training, 53 DEGs were found at peak exercise (V24T1) compared to rest (V24T0), including three upregulated genes (ANK3, FTO, FCN1) and 50 downregulated genes (TOP 5: MYL9, NRGN, H2AC6, MAP3K7CL, B2M). These genes were primarily involved in inflammation and metabolism. Pathway analysis revealed significant regulation of 100 pathways at post-training compared to pre training, predominantly inactivated, including pathways involved in inflammation (STAT3 signaling) and metabolism (O-linked glycosylation). Acute exercise and exercise training modulated EV-associated gene expression in long COVID, primarily through transcriptional downregulation. Suppression of inflammation- and immune-related genes post-training highlights potential molecular mechanisms underlying symptom improvement and identifies candidate biomarkers of recovery biology in long COVID. Importantly, while exercise training did not substantially alter EV RNA content at rest, it enhanced the body's ability to mount a dynamic EV-mediated molecular response during exertion, reflecting improved physiological adaptability.Clinical trial registration number: NCT05398692.},
}

Humans
*Extracellular Vesicles/genetics/metabolism
*COVID-19/genetics/blood/virology
Male
Female
Middle Aged
*Exercise/physiology
SARS-CoV-2/genetics
Adult
Pilot Projects
Gene Expression Regulation

@article {pmid41586458,
year = {2026},
author = {Horton, M and Smith, AB and Milne, R and Winch, D and Rayner, C and Halpin, S and O'Connor, R and Rocha Lawrence, R and Greenwood, DC and Bakerly, ND and Evans, R and Kwon, J and Dawes, H and Wood, C and Williams, P and Master, H and Mansoubi, M and De Kock, JH and Mullard, J and Ormerod, M and Mir, G and Petrou, S and O'Connor, DB and Sivan, M and , },
title = {Large-Scale Psychometric Assessment and Validation of the Modified COVID-19 Yorkshire Rehabilitation Scale Patient-Reported Outcome Measure for Long COVID or Post-COVID Syndrome.},
journal = {Journal of medical virology},
volume = {98},
number = {2},
pages = {e70816},
doi = {10.1002/jmv.70816},
pmid = {41586458},
issn = {1096-9071},
support = {COV-LT2-0016//National Institute for Health and Care Research award/ ; },
mesh = {Humans ; Female ; Male ; *Psychometrics/methods ; *COVID-19/rehabilitation/psychology ; Middle Aged ; *Patient Reported Outcome Measures ; Adult ; Reproducibility of Results ; Aged ; SARS-CoV-2 ; Severity of Illness Index ; Surveys and Questionnaires ; },
abstract = {The C19-YRS was the first condition-specific for long COVID/post-COVID syndrome. Although the original C19-YRS evolved to the modified version (C19-YRSm) based on psychometric evidence, clinical content relevance, as well as feedback from patients and healthcare professionals, it has not been validated through Rasch analysis. The study aim was to psychometrically assess and validate the C19-YRSm using newly collected data from a large-scale, multicenter study (LOCOMOTION). In total, 1278 patients (67% Female; mean age = 48.6, SD 12.7) digitally completed the C19-YRSm. The psychometric properties of the C19-YRSm Symptom Severity (SS) and Functional Disability (FD) subscales were assessed using a Rasch Measurement Theory framework, assessing for individual item model fit, targeting, internal consistency reliability, unidimensionality, local dependency (LD), response category functioning and differential item functioning (DIF) by age group, sex and ethnicity. Rasch analysis revealed robust psychometric properties of both subscales, with each demonstrating unidimensionality, appropriate response category structuring, no floor or ceiling effects, and minimal LD and DIF. Both subscales also displayed good targeting and reliability (SS: Person Separation Index (PSI) = 0.81, Cronbach's α = 0.82; FD: PSI = 0.76, Cronbach's α = 0.81). Although some minor anomalies are apparent, the modifications to the original C19-YRS have strengthened its measurement characteristics and its clinical and conceptual relevance. Trial Registration: NCT05057260, ISRCTN15022307.},
}

Humans
Female
Male
*Psychometrics/methods
*COVID-19/rehabilitation/psychology
Middle Aged
*Patient Reported Outcome Measures
Adult
Reproducibility of Results
Aged
SARS-CoV-2
Severity of Illness Index
Surveys and Questionnaires

@article {pmid41585473,
year = {2026},
author = {Zhang, J and Chen, Y and Zhang, A and Yang, Y and Ma, L and Yu, K and Zhang, W and Ye, X and Zhang, J and Lin, K and Lin, X},
title = {Interpretable machine learning for predicting low-dose methylprednisolone effectiveness in long COVID.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114574},
pmid = {41585473},
issn = {2589-0042},
abstract = {Long COVID is a chronic, multisystem disease with limited response to conventional treatments. While low-dose methylprednisolone has shown effectiveness in some patients, individual responses vary, and accurate predictive tools are lacking. This retrospective study included 330 long COVID patients who received low-dose methylprednisolone treatment across three hospitals. Patients were divided into training (n = 202), test (n = 33), and external validation sets (n = 53, n = 42). Using least absolute shrinkage and selection operator (LASSO) regression, 38 variables were analyzed to develop six machine learning models. The logistic regression (LR) model showed stable performance across all datasets (AUCs: 0.8715, 0.7198, 0.8419, and 0.8676), making it the final model selected. SHapley Additive exPlanations (SHAP) analysis identified seven key variables, which were used to construct a nomogram for predicting treatment efficacy. The LR model and nomogram demonstrated strong predictive performance and clinical interpretability, offering a valuable decision-support tool for individualized treatment of long COVID with low-dose methylprednisolone.},
}

@article {pmid41584202,
year = {2025},
author = {Wen, J and Yuan, L and Zhang, L and Li, L and Chen, J and Zhang, Z and Yan, Y},
title = {Distribution of acute symptoms and long COVID-19 and their association with anxiety and depression 2 years after infection.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1687444},
pmid = {41584202},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; Male ; *Anxiety/epidemiology ; Female ; Retrospective Studies ; Adult ; *Depression/epidemiology ; Cross-Sectional Studies ; Middle Aged ; *Health Personnel/psychology/statistics & numerical data ; Surveys and Questionnaires ; SARS-CoV-2 ; Prevalence ; },
abstract = {BACKGROUND: With the continuing impact of the COVID-19 outbreak, the mental health of infected patients is becoming a widespread concern. However, the relationship between acute-phase symptoms and long COVID-19 symptoms with anxiety and depression 2 years post-infection among healthcare workers remains unclear.

OBJECTIVE: The aim of this study was to investigate the relationship between acute phase symptoms and long COVID-19 symptoms of novel COVID-19 infection and anxiety and depression 2 years after infection.

METHODS: Using a retrospective cohort study and cross-sectional design, this study collected data on acute-phase symptoms, long COVID-19 symptoms, and their levels of anxiety and depression from 1,038 COVID-19 patients by questionnaire. We explored their relationship through logistic regression. We also used RCS curves to explore the nonlinear relationship between acute phase symptoms and long COVID-19 symptoms and anxiety and depression 2 years after infection.

RESULTS: The aim of this study was to investigate the prevalence of common symptoms of long COVID-19 in a sample of medical staff with COVID-19 infection. The study also aimed to explore the relationship between long COVID-19 symptoms and mental health status. The results showed that among patients who tested positive for COVID-19 by December 2022, approximately 34.0% exhibited overall long COVID-19 symptoms 2 years after infection. Decreased concentration and memory were the most common long COVID-19 symptoms, accounting for 12.5% of all COVID-19 patients. In this study, we also explored the relationship between acute-phase symptoms or long COVID-19 symptoms and anxiety and depression 2 years after infection. The findings showed that both acute phase symptoms as well as long COVID-19 symptoms were significantly associated with levels of anxiety and depression 2 years after infection. We also found a nonlinear relationship between the number of long COVID-19 symptoms and anxiety and depression.

CONCLUSION: In summary, the positive correlation between the acute phase of COVID-19 infection and the impact of long COVID-19 symptoms on mental health suggests that focusing on the mental health of patients recovering from the epidemic is critical. Effective psychological interventions should be part of the comprehensive treatment of long COVID-19 to help patients improve their mental health while recovering physically.},
}

Humans
*COVID-19/psychology/epidemiology/complications
Male
*Anxiety/epidemiology
Female
Retrospective Studies
Adult
*Depression/epidemiology
Cross-Sectional Studies
Middle Aged
*Health Personnel/psychology/statistics & numerical data
Surveys and Questionnaires
SARS-CoV-2
Prevalence

@article {pmid41582616,
year = {2026},
author = {Tmava, A and Burstein, EM},
title = {A call for a critical medical anthropology of the COVID-19 pandemic.},
journal = {Anthropology & medicine},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/13648470.2025.2604010},
pmid = {41582616},
issn = {1469-2910},
abstract = {This paper is a call for a renewed critical medical anthropology (CMA) of the COVID-19 pandemic, one that attends not only to the pandemic's acute phase but also to its enduring afterlife. We argue that COVID-19 persists as a structuring condition that continues to impact individual experiences as well as domestic and global politics and culture. We introduce the concept of 'narrative compression' to describe how public and institutional discourses have foreclosed space for the ongoing suffering of individuals with long COVID and others marginalized by pandemic legacies. By tracing how closure is epistemically and politically produced, this paper reframes COVID-19 as an ambient and persistent crisis. We advocate for an anthropological approach that remains with the pandemic to diagnose its transformations and imagine more accountable health futures.},
}

@article {pmid41583965,
year = {2023},
author = {Lee, H and Seo, Y and Kim, J and Song, HY and Park, J and Yang, Y},
title = {The impact of Long COVID, work stress related to infectious diseases, fatigue, and coping on burnout among care providers in nursing home: A cross-sectional correlation study.},
journal = {Journal of Korean gerontological nursing},
volume = {25},
number = {3},
pages = {271-283},
pmid = {41583965},
issn = {2383-8086},
abstract = {PURPOSE: An increasing number of nursing home are being established because of the increased demand for treatment and care of older adults with chronic diseases related to population aging. This study aimed to examine the impact of long COVID, infectious diseases-related to work stress, fatigue, and coping on burnout among care providers in nursing home during the persistent COVID-19 pandemic.

METHODS: A total of 168 care providers, including nurses, nursing assistants, and caregivers working in nursing home between July 22 and August 12, 2022 were polled by a questionnaire survey. The collected data were analyzed using an independent t-test, one-way analysis of variance, Scheffé test, Pearson correlation coefficient, and multiple regression analyses via SPSS 21.0.

RESULTS: The prevalence of Long COVID-19 among care providers in nursing home was 85.7%, with a mean burnout score of 2.59 out of 5. Work stress related to infectious diseases (β=.27, p=.002) and infection control fatigue (e.g., fatigue related to complexity of nursing duties and shortage in employees [β=.51, p=.019], conflicts caused by uncertain situations and a lack of support [β=.50, p=.012]) were the variables that significantly associated with burnout.

CONCLUSION: It is crucial to actively explore strategies for reducing overall work stress, anxiety, and fatigue, particularly related to infection management to alleviate burnout among care providers in nursing home. Our findings provide fundamental data for the development of interventions and policies to prevent care providers' burnout, thus enabling the provision of high-quality care in nursing home.},
}

@article {pmid41581925,
year = {2026},
author = {Keat, SBK and Khatri, P and Ali, YM and Arachchilage, CH and Demopulos, G and Baillie, K and Miners, KL and Ladell, K and Jones, SA and Davies, HE and Price, DA and Zelek, WM and Morgan, BP and Schwaeble, WJ and Lynch, NJ},
title = {Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.},
journal = {Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imm.70110},
pmid = {41581925},
issn = {1365-2567},
support = {//UK Dementia Research Institute/ ; COV0170//National Institute for Health and Care Research/ ; COV-LT2-0041//National Institute for Health and Care Research/ ; //Omeros Corporation/ ; Balvi B43//PolyBio Research Foundation/ ; 520488//Race against Dementia Alzheimer's Research/ ; },
abstract = {Long COVID affects a substantial proportion of survivors of acute infection with severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), who suffer a variety of symptoms that limit their quality of life and economic activity. Although the aetiology of long COVID is obscure, it appears to be a chronic inflammatory condition. Complement dysregulation is a prevalent feature of long COVID. Specifically, markers of classical, alternative, and terminal pathway activation are often elevated in patients with this condition. Here, we used a sensitive assay for mannan-binding lectin-associated serine protease-2 (MASP-2)/C1Inh complexes to analyse lectin pathway activation in a previously characterised cohort of patients with long COVID (n = 159) and healthy convalescent individuals with no persistent symptoms after infection with SARS-CoV-2 (n = 76). The data were combined with those from the most predictive complement analytes identified previously to delineate potential biomarkers of long COVID. MASP-2/C1Inh complexes were significantly elevated in patients with long COVID (p = 0.0003). Generalised linear modelling further identified an optimal set of four markers, namely iC3b (alternative pathway), TCC (terminal pathway), MASP-2/C1Inh (lectin pathway), and the complement regulator properdin, which had a receiver operating characteristic predictive power of 0.796 (95% confidence interval = 0.664-0.905). Combinations of the classical pathway markers C4, C1q, and C1s/C1Inh were poorly predictive of long COVID. These findings demonstrate that activation of the lectin complement pathway, which occurs upstream of the alternative and terminal pathways and can be inhibited therapeutically, is a salient feature of long COVID.},
}

@article {pmid41581648,
year = {2026},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Natural History of Self-reported Symptoms Following SARS-CoV-2 Infection: A Target Trial Emulation in a Prospective Community-recruited Cohort.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108422},
doi = {10.1016/j.ijid.2026.108422},
pmid = {41581648},
issn = {1878-3511},
abstract = {BACKGROUND: Using a prospective, community-recruited cohort with data on background symptom prevalence and repeated longitudinal symptom assessments, we estimated post-infection risks of long COVID symptoms compared with contemporaneous uninfected controls.

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

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

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

@article {pmid41580734,
year = {2026},
author = {Fang, H and Wang, Q},
title = {The silent epidemic within the pandemic: pathophysiology and prediction of post-COVID-19 diabetes.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07717-x},
pmid = {41580734},
issn = {1479-5876},
}

@article {pmid41580699,
year = {2026},
author = {Mou, K and Gao, Y and Zhang, Y and Man, S and Chen, Q and Xu, H and Chen, Y and Zhang, M},
title = {Long-term retinal dysfunction following COVID-19 infection: a one-year prospective observational study.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-025-04575-x},
pmid = {41580699},
issn = {1471-2415},
support = {2023HXFH043//1·3·5 project for disciplines of excellence-Clinical Research Fund, West China Hospital, Sichuan University/ ; },
}

@article {pmid41580590,
year = {2026},
author = {Mischke, M and Zaehle, T},
title = {Modulating subjective and objective cognitive state fatigue in long COVID with repetitive anodal tDCS: results from a double-blinded randomized controlled trial.},
journal = {BMC neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12868-025-00989-x},
pmid = {41580590},
issn = {1471-2202},
abstract = {BACKGROUND: Cognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) has been proposed as a promising approach to modulate fatigue-related neural networks. To comprehensively assess cognitive fatigue, the integration of subjective and objective behavioral and electrophysiological measures of induced state fatigue is essential.

METHODS: This double-blind, randomized, sham-controlled study investigated the effects of four consecutive daily sessions of 30-minute anodal tDCS over the left dlPFC on subjective and objective markers of cognitive state fatigue in individuals with long COVID. The present paper focuses on secondary outcomes, including subjective state fatigue ratings via visual analogue scales, behavioral performance indices, and electrophysiological markers such as temporal alterations of frontal theta and occipital alpha activity as well as p50 sensory gating.

RESULTS: Forty participants received either verum or sham tDCS while completing a gamified adaptive Go/No-Go task. Before and after the stimulation period, cognitive state fatigue was reliably induced using the AX-Continuous Performance Task (AX-CPT). Although tDCS did not significantly affect subjective state-fatigue ratings or behavioral performance, our findings indicate that verum stimulation may stabilize fatigue-related changes in occipital alpha power. No immediate stimulation-related improvements were found in the Go/No-Go task.

CONCLUSIONS: These findings indicate that while tDCS may modulate neurophysiological correlates of cognitive state fatigue, its impact on subjective experience and behavioral performance remain limited under the current protocol. These results, however, underscore the importance of including neurophysiological endpoints in intervention research and highlight the need for developing more robust and individualized stimulation protocols. Future studies should consider extended stimulation regimens, alternative task paradigms, and more sensitive behavioral measures to further elucidate the neuromodulatory potential of tDCS in long COVID-related cognitive fatigue.

TRIAL REGISTRATION: drks.de Identifier: DRKS00031294, date of registration: 17.02.2023.},
}

@article {pmid41578033,
year = {2026},
author = {Aid, M and Boero-Teyssier, V and McMahan, K and Dang, R and Doyle, M and Belabbaci, N and Borducchi, E and Collier, AY and Mullington, J and Barouch, DH},
title = {Author Correction: Long COVID involves activation of proinflammatory and immune exhaustion pathways.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41590-026-02438-1},
pmid = {41578033},
issn = {1529-2916},
}

@article {pmid41577420,
year = {2026},
author = {Schuster, AM and Alwan, NA and Callard, F and Chen, EYH and Gilbody, S and Graham, BM and Hatch, SL and Jones, E and Jordan, A and Knapp, M and López-Jaramillo, C and Nakimuli-Mpungu, E and Pathare, S and Ressler, KJ and Wessely, S and White, LA and , and Jones, PB},
title = {The implications of the COVID-19 pandemic for clinical mental health care.},
journal = {The lancet. Psychiatry},
volume = {13},
number = {2},
pages = {140-161},
doi = {10.1016/S2215-0366(25)00247-0},
pmid = {41577420},
issn = {2215-0374},
mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Mental Health Services/organization & administration ; *Mental Disorders/therapy/epidemiology ; Pandemics ; SARS-CoV-2 ; Mental Health ; },
abstract = {A Position Paper published in The Lancet Psychiatry in 2020 suggested an agenda for research about the effects of the COVID-19 pandemic on mental health, following which an interdisciplinary Lancet Psychiatry standing commission was established in 2022 to examine the emerging evidence and refine recommendations for more research. In this first Series paper from the standing commission, we focus on changes in the delivery of clinical mental health care during the COVID-19 pandemic. The second paper in the Series focuses on public mental health and policy perspectives, and the third will address neuropsychiatric consequences of infection by SARS-CoV-2. Evidence from high-quality longitudinal studies with pre-pandemic baseline data, controlled intervention trials, or systematic reviews took time to accrue. During the early months of the COVID-19 pandemic, symptoms of anxiety and depression became more prevalent, and many mental health services were compromised by pandemic-related factors; however, whether the COVID-19 pandemic accelerated pre-existing long-term trends of increasing incidence of mental health disorders, especially in children and adolescents, is unclear. Little research has been done in low-income and middle-income countries, or regarding post-COVID-19 condition (also known as long COVID), which emerged as a multisystem condition with mental health implications. Vulnerable populations, including socioeconomically disadvantaged and minoritised groups, faced disproportionate mental health impacts and limited access to care during the COVID-19 pandemic, reflecting systemic, pre-pandemic inequalities. Bold implementation of existing evidence-based mental health support for vulnerable communities, ambitious trials of novel interventions, and systematic pooling of rapidly accumulating evidence about best healh care should be priorities in future pandemics.},
}

Humans
*COVID-19/psychology/epidemiology
*Mental Health Services/organization & administration
*Mental Disorders/therapy/epidemiology
Pandemics
SARS-CoV-2
Mental Health

@article {pmid41576003,
year = {2026},
author = {Novak, P and Systrom, DM and Witte, A and Marciano, SP and Felsenstein, D and Milunsky, JM and Milunsky, A and Krier, J and Fishman, MC},
title = {Shared autonomic phenotype of long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0341278},
doi = {10.1371/journal.pone.0341278},
pmid = {41576003},
issn = {1932-6203},
mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology ; Female ; *COVID-19/physiopathology/complications ; Male ; Middle Aged ; Adult ; Retrospective Studies ; *Autonomic Nervous System/physiopathology ; Phenotype ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are relatively common and disabling multisystem disorders that share overlapping features, including post-infectious onset and similar clinical manifestations such as brain fog, fatigue, muscle pain, and dysautonomia with orthostatic intolerance. These similarities suggest that Long COVID and ME/CFS may share common pathophysiological mechanisms, though the underlying mechanisms remain poorly understood, partly due to the difficulty in quantifying many of the symptoms.

MATERIALS AND METHODS: This retrospective study evaluated Long COVID and pre-COVID ME/CFS patients who completed autonomic testing between 2018 and 2023 at the Brigham and Women's Faulkner Hospital Autonomic Laboratory. The evaluations included autonomic tests (Valsalva maneuver, deep breathing, tilt-table test, and sudomotor function) with capnography and transcranial Doppler monitoring of cerebral blood flow velocity (CBFv) in the middle cerebral artery, neuropathic assessment through skin biopsies for small fiber neuropathy (SFN), invasive cardiopulmonary exercise testing (ICPET), and laboratory analyses covering metabolic, inflammatory, autoimmune, and hormonal profiles.

RESULTS: A total of 143 Long COVID and 170 ME/CFS patients were analyzed and compared to 73 healthy controls and 290 patients with hypermobile Ehlers-Danlos syndrome (hEDS). Tests revealed extensive similarities between Long COVID and ME/CFS, including reduced orthostatic CBFv (92%/88% in Long COVID/ME/CFS), mild-to-moderate widespread autonomic failure (95%/89%), presence of SFN (67%/53%), postural tachycardia syndrome (POTS) (22%/19%), neurogenic orthostatic hypotension (15%/15%) and preload failure (96%/92%, assessed in 25/66 Long COVID/ME/CFS). Patients with hEDS exhibited more severe peripheral neurodegeneration compared to the other groups. Laboratory tests did not distinguish between the conditions.

CONCLUSION: Both Long COVID and ME/CFS demonstrate dysregulation in cerebrovascular blood flow, autonomic reflexes, and small fiber neuropathy, suggesting that these conditions may share a common underlying pathophysiology. However, differing distributions of findings in patients with hEDS raise the question of whether these conditions represent distinct but overlapping syndromes or reflect a shared underlying pathway. Further research is required to clarify the relationship between these conditions and the potential underlying pathophysiological mechanisms.},
}

Humans
*Fatigue Syndrome, Chronic/physiopathology
Female
*COVID-19/physiopathology/complications
Male
Middle Aged
Adult
Retrospective Studies
*Autonomic Nervous System/physiopathology
Phenotype
SARS-CoV-2

@article {pmid41573552,
year = {2025},
author = {Perico, L and Bovio, A and Tomasoni, S and Trionfini, P and Cerullo, D and Corna, D and Pezzotta, A and Locatelli, M and Alberti, M and Benigni, A and Remuzzi, G},
title = {Acetylsalicylic acid disrupts SARS-CoV-2 spike protein glycosylation and selectively impairs binding to ACE2.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1706997},
pmid = {41573552},
issn = {1664-3224},
mesh = {*Spike Glycoprotein, Coronavirus/metabolism ; Animals ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; Glycosylation/drug effects ; *SARS-CoV-2/drug effects/metabolism ; *Aspirin/pharmacology ; Humans ; Vero Cells ; Mice ; Chlorocebus aethiops ; COVID-19/metabolism/virology ; Mice, Transgenic ; Protein Binding/drug effects ; *COVID-19 Drug Treatment ; },
abstract = {Preclinical and clinical evidence suggested the potential benefits of treatment with acetylsalicylic acid (ASA) in mitigating COVID-19 severity. While available studies largely focused on the intracellular pathways through which ASA impairs viral replication or dampens host immunoresponse stimulated by SARS-CoV-2, whether ASA directly affects the interaction between the viral spike protein and its cellular receptor angiotensin converting enzyme 2 (ACE2) remains unexplored. This question is clinically relevant, as circulating spike S1 has been shown to persist in patients with acute and long COVID-19, where its interaction with the broadly expressed ACE2 drives systemic manifestations and tissue damage. Here, we demonstrate that pre-incubation of the SARS-CoV-2 spike subunit 1 (S1) with ASA dose-dependently impaired ACE2 binding on Vero cells. The functional relevance of this finding was confirmed in transgenic mice with human ACE2, in which intratracheal administration of ASA-treated S1 markedly reduced lung injury, fibrosis, and inflammation compared to untreated S1. Glycoproteomic profiling revealed that ASA altered the glycosylation landscape of S1, particularly N-glycosylation at N61 and O-glycosylation at S325. Site-directed mutagenesis of these two residues confirmed the critical role of their glycosylation in S1-ACE2 binding in vitro. Consistently, the glycosylation-insensitive S1 had limited effect in inducing lung injury, fibrosis, and inflammation in transgenic mice compared to WT S1, phenocopying the protective effects of ASA. These findings unveil a previously unrecognized antiviral activity of ASA, providing a molecular rationale for its repurposing as a low-cost, readily available intervention to prevent the progression from mild to severe COVID-19.},
}

*Spike Glycoprotein, Coronavirus/metabolism
Animals
*Angiotensin-Converting Enzyme 2/metabolism/genetics
Glycosylation/drug effects
*SARS-CoV-2/drug effects/metabolism
*Aspirin/pharmacology
Humans
Vero Cells
Mice
Chlorocebus aethiops
COVID-19/metabolism/virology
Mice, Transgenic
Protein Binding/drug effects
*COVID-19 Drug Treatment

@article {pmid41573029,
year = {2025},
author = {Dirwanto, L and Ali, D and Japaries, W and Agussalim, WS},
title = {Effectiveness of Transcutaneous Electrical Acupoint Stimulation in the Treatment of Post-COVID Severe Dyspnea: A Case Report.},
journal = {Medical acupuncture},
volume = {37},
number = {5},
pages = {408-411},
pmid = {41573029},
issn = {1933-6586},
abstract = {INTRODUCTION: Long COVID, or post-COVID syndrome, refers to signs, symptoms, and conditions that persist or emerge following an acute coronavirus disease (COVID-19) infection. The most frequent symptoms are fatigue and dyspnea, with approximately 10-20% of patients recovering from COVID-19. Currently, there are no specific medical recommendations, except for symptomatic treatment.

OBJECTIVE: To evaluate the use of transcutaneous electrical acupoint stimulation (TEAS) for the treatment of post-COVID severe dyspnea.

METHODOLOGY: This is a case report of successful treatment using TEAS in a patient with severe dyspnea after recovery from COVID-19.

RESULTS: A female adult patient experienced progressive dyspnea after recovering from COVID-19 a year prior. One session of TEAS successfully relieved severe dyspnea. No adverse effects or recurrence of dyspnea were reported at the 6-month follow-up.

CONCLUSION: TEAS is a safe, simple, and effective treatment for overcoming post-COVID severe dyspnea.},
}

@article {pmid41570188,
year = {2025},
author = {Ford, ND and Simeone, RM and Pratt, C and Saydah, S},
title = {Functional Limitations and Illness-Related Absenteeism among School-Aged Children with and without Long COVID, United States, 2022-2023.},
journal = {Emerging infectious diseases},
volume = {31},
number = {14},
pages = {11-19},
doi = {10.3201/eid3114.251035},
pmid = {41570188},
issn = {1080-6059},
mesh = {Humans ; Child ; *Absenteeism ; *COVID-19/epidemiology ; Adolescent ; Male ; Female ; United States/epidemiology ; Cross-Sectional Studies ; Child, Preschool ; SARS-CoV-2 ; Schools ; Pandemics ; },
abstract = {We examined functional limitations and illness-related chronic absenteeism (i.e., missing >18 days of school for health reasons) in a cross-sectional nationally representative sample of 11,057 US children 5-17 years of age who ever or never had long COVID (i.e., symptoms lasting >3 months after COVID-19 illness). Among 4,587 children with prior COVID-19, we estimated whether long COVID was associated with increased illness-related chronic absenteeism by using logistic regression. Our analysis showed that ≈1.4% of school-aged children had long COVID at some point. Among children with prior COVID-19, those who had long COVID at some point more frequently reported functional limitations, such as difficulty with memory, than those who did not have long COVID (18.3% vs. 8.6%). Having long COVID was associated with higher odds of illness-related chronic absenteeism. Children who had long COVID could experience functional limitations and absenteeism. School accommodations might be an option to improve functional limitations.},
}

Humans
Child
*Absenteeism
*COVID-19/epidemiology
Adolescent
Male
Female
United States/epidemiology
Cross-Sectional Studies
Child, Preschool
SARS-CoV-2
Schools
Pandemics

@article {pmid41570186,
year = {2025},
author = {Pratt, CQ and Dalton, AF and Koumans, EH and Agedew, A and Coronado, F and Lundeen, EA and Woodruff, RC and Block, JP and Weiner, M and Cowell, L and Arnold, JD and Saydah, S and , },
title = {Thrombotic Events and Stroke in the Year After COVID-19 or Other Acute Respiratory Infection.},
journal = {Emerging infectious diseases},
volume = {31},
number = {14},
pages = {3-10},
doi = {10.3201/eid3114.250630},
pmid = {41570186},
issn = {1080-6059},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Stroke/epidemiology/etiology ; Male ; *Thrombosis/epidemiology/etiology ; Female ; *Respiratory Tract Infections/complications/epidemiology ; Middle Aged ; Aged ; Incidence ; SARS-CoV-2 ; Adult ; Risk Factors ; Hospitalization ; Aged, 80 and over ; },
abstract = {Previous studies have documented an increased risk for thrombotic events 30 days after COVID-19 infection, but less is known about this risk beyond 30 days or compared with risk after other infectious acute respiratory illnesses (ARIs). By using PCORnet data from April 1, 2022-April 30, 2023, we compared the incidences of thrombotic events in the year after COVID-19 illness with other ARI diagnoses in hospitalized and nonhospitalized patients. Overall, the risk for any thrombotic event was higher among patients with COVID-19 compared with patients with other ARIs (incidence ratio 1.63; p<0.05). Nonhospitalized patients with COVID-19 had a 73% increased risk for a thrombotic event in the year after acute illness compared with nonhospitalized patients with ARI (p<0.05). The increased risk for thrombotic events in the year after COVID-19 emphasizes the need for stroke awareness for patients and healthcare professionals.},
}

Humans
*COVID-19/complications/epidemiology
*Stroke/epidemiology/etiology
Male
*Thrombosis/epidemiology/etiology
Female
*Respiratory Tract Infections/complications/epidemiology
Middle Aged
Aged
Incidence
SARS-CoV-2
Adult
Risk Factors
Hospitalization
Aged, 80 and over

@article {pmid41570177,
year = {2025},
author = {Fiore, AE},
title = {Progress Toward Understanding Infection-Associated Chronic Conditions and Illnesses.},
journal = {Emerging infectious diseases},
volume = {31},
number = {14},
pages = {1-2},
doi = {10.3201/eid3114.251187},
pmid = {41570177},
issn = {1080-6059},
}

@article {pmid41569391,
year = {2026},
author = {Raymond, KF and Hodge, T and St Jean, B and Liu, BF},
title = {Barriers to Long COVID Care in the U.S.: An Application of Levesque et al.'s Access Framework.},
journal = {Health care analysis : HCA : journal of health philosophy and policy},
volume = {},
number = {},
pages = {},
pmid = {41569391},
issn = {1573-3394},
support = {Pandemic Readiness Initiative//University of Maryland/ ; Pandemic Readiness Initiative//University of Maryland/ ; },
abstract = {Long COVID is a condition that arose during the COVID-19 pandemic in individuals who developed the multi-system chronic condition after a COVID-19 infection. During the pandemic in the United States (U.S.), these "COVID long-haulers" navigated a complex and overburdened health care system in pursuit of diagnoses and treatments. This qualitative secondary analysis used the 2013 Levesque et al. Conceptual Model of Healthcare Access to examine multidimensional health care access issues faced by 29 COVID long-haulers in the U.S. Our analysis showed that long-haulers faced complementary issues from both individual and health systems perspectives related to the inability to get diagnoses or treatments, long waiting times for providers and difficulty reaching services, underinformed providers and biased interpersonal experiences, and struggles with the financial costs of treating the condition, which impacted care decisions. Interviewees also described relying on alternative medicine to provide symptom relief. Overall, this study extends international research by offering a comprehensive examination of Long COVID health care access issues in the U.S. and identifying specific insights related to health care access that made obtaining Long COVID care difficult, such as the mismatch between individual expectations of what health care should look like and how it actually operates. Our use of the full Conceptual Model of Healthcare Access provides new insights into the overlap across layers of access issues and offers suggestions for how public health and clinical health practitioners can collaborate to meet the needs of vulnerable populations such as these in future health emergencies.},
}

@article {pmid41568000,
year = {2025},
author = {Camici, M and Franco, M and Talamanca, L and Petino, M and Paulicelli, J and Scarnecchia, L and Ciavarella, L and Orzilli, T and Balducelli, F and Mazzotta, V and Mastrorosa, I and Cimini, E and Tartaglia, E and Notari, S and Maggi, F and Girardi, E and Baldelli, R and Zuppi, P and Antinori, A},
title = {Salivary cortisol in long COVID: a marker of broader stress system and circadian rhythm dysregulation.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1690698},
pmid = {41568000},
issn = {2235-2988},
mesh = {Humans ; *Hydrocortisone/analysis/metabolism ; *Saliva/chemistry ; Female ; *COVID-19/metabolism/physiopathology/complications ; Middle Aged ; Male ; *Circadian Rhythm/physiology ; Prospective Studies ; Case-Control Studies ; Aged ; Hypothalamo-Hypophyseal System/physiopathology ; Pituitary-Adrenal System/physiopathology ; SARS-CoV-2 ; Biomarkers/analysis ; Adult ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long COVID (LC) has been associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, although findings from blood cortisol measurements remain inconsistent. We hypothesized that LC patients exhibit a disrupted diurnal cortisol rhythm and that salivary cortisol (SC) profiling may provide a more accurate assessment of HPA activity.

METHODS: This prospective, single-center, case-control study was conducted at a Long COVID clinic in Rome between February 2023 and March 2024 and included 96 participants evaluated at least 28 days after confirmed SARS-CoV-2 infection. LC was defined as one or more new or persistent symptoms and classified as severe when four or more of the following were present: fatigue, cognitive impairment, exercise intolerance, dyspnea, arthralgia, or dysautonomia. SC was measured at 8:00 AM, 3:00 PM, and 11:00 PM.

RESULTS: The cohort (mean age 58.1 ± 14.8 years; 60% female; all White) included 83 LC patients (80% moderate, 20% severe) and 13 asymptomatic post-COVID (APC) individuals. Compared with healthy controls, both LC and APC groups showed reduced morning SC (p<0.01), flattened diurnal variation, and elevated evening SC, indicating loss of the normal morning peak and nocturnal decline. Blood cortisol levels did not differ among groups, but LC patients had higher ACTH than APC (26 pg/mL vs 13 pg/mL; p<0.01), suggesting compensatory HPA activation. One LC patient (1.2%) was diagnosed with adrenal insufficiency.

DISCUSSION: These exploratory findings suggest a disrupted circadian cortisol rhythm in individuals after COVID-19, with altered HPA axis dynamics that may be associated with disease severity.},
}

Humans
*Hydrocortisone/analysis/metabolism
*Saliva/chemistry
Female
*COVID-19/metabolism/physiopathology/complications
Middle Aged
Male
*Circadian Rhythm/physiology
Prospective Studies
Case-Control Studies
Aged
Hypothalamo-Hypophyseal System/physiopathology
Pituitary-Adrenal System/physiopathology
SARS-CoV-2
Biomarkers/analysis
Adult
Post-Acute COVID-19 Syndrome

@article {pmid41566432,
year = {2026},
author = {Gottlieb, M and Yu, H and Chen, J and Spatz, ES and Gentile, NL and Geyer, RE and Santangelo, M and Malicki, C and Gatling, K and O'Laughlin, KN and Stephens, KA and Elmore, JG and Wisk, LE and L'Hommedieu, M and Rodriguez, RM and Montoy, JCC and Wang, RC and Rising, KL and Kean, E and Dyal, JW and Hill, MJ and Venkatesh, AK and Weinstein, RA and , },
title = {Obesity and Long COVID: intersecting epidemics?.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-025-26134-1},
pmid = {41566432},
issn = {1471-2458},
support = {75D30120C08008/CC/CDC HHS/United States ; },
}

@article {pmid41566332,
year = {2026},
author = {Penuelas, VL and Pham, K and Frost, S and Harahap-Carrillo, IS and Vargas, A and Bergersen, KV and He, Y and Nair, MG and Kaul, M and Heinrich, EC},
title = {Long-term impacts of COVID-19 on systemic inflammation and control of breathing reflexes: an observational cohort study.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-025-03473-6},
pmid = {41566332},
issn = {1465-993X},
abstract = {BACKGROUND: The COVID-19 pandemic resulted in over 7 million reported deaths and over 700.4 million reported infections to-date. Many individuals who recover from COVID-19 report prolonged dyspnea, sometimes persisting for months. Furthermore, COVID-19 has been linked to systemic and neuronal inflammation which may have downstream impacts on the neural control of breathing. Therefore, we hypothesized that individuals recovered from COVID-19 may exhibit changes in their ventilatory chemosensitivity to carbon dioxide and hypoxia, and that these changes may be linked to systemic inflammation.

METHODS: To test this hypothesis, we measured baseline ventilatory patterns and chemoreflex sensitivity in individuals recovered from COVID-19 (n = 77) and individuals with no prior COVID-19 infection (n = 41). Peripheral venous blood samples were also collected for inflammatory biomarker expression and profiling.

RESULTS: Recovered participants demonstrated a small but progressive decrease in the hypercapnic ventilatory response under a co-stimulus with hypoxia (control vs. 24-month post-recovery; p = 0.023). Additionally, we identified several significant correlations between plasma inflammatory markers and ventilatory chemoreflex characteristics, including a positive correlation between SAA and CRP and the ventilatory response to hypoxia (p < 0.05 within recovered and control cohorts). Finally, expression of six vascular inflammatory markers (Myoglobin, NGAL, MMP-2, OPN, IGFBP-4, and Cystatin C) was unexpectedly decreased in recovered participants compared to the control cohort for up to one-year post recovery.

CONCLUSIONS: Overall, this data indicates that COVID-19 and other acute viral infections may have a modest impact on the chemoreflex control of breathing as well as systemic inflammatory profiles, and that these changes may be linked to each other. These findings may strengthen our understanding of the pathology of long-COVID symptoms.},
}

@article {pmid41565056,
year = {2026},
author = {Uematsu, T and Nojiri, S and Nagao, M and Ishijima, M and Nishizaki, Y},
title = {Comprehensive analysis of risk factors for Coronavirus disease 2019 infection and post-infection sequelae based on real-world data from a health insurance database in Japan.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108405},
doi = {10.1016/j.ijid.2026.108405},
pmid = {41565056},
issn = {1878-3511},
abstract = {OBJECTIVES: Using real-world data from Japan, this study aimed to examine disease risks in COVID-19 patients before and after infection.

METHODS: We used the Japanese Health Insurance Database to identify hospitalized patients in Japan aged 60 years who were newly diagnosed with COVID-19 by December 31, 2020. To form the study population, these patients were matched 1:1 with individuals without COVID-19 on the basis of age, sex, and index date. Two analytical approaches were employed: a case-control study using conditional logistic least absolute shrinkage and selection operator (LASSO) regression to identify risk factors for COVID-19 infection and a retrospective cohort study using time-to-event analysis to evaluate the risk of developing sequelae following infection.

RESULTS: Overall, 8,072 patients were included (4,036 in each group). Organic, including symptomatic mental disorders demonstrated the strongest association (odds ratio, 2.276). Following infection, behavioral syndromes associated with physiological disturbances and physical factors exhibited the highest risk of developing new conditions (hazard ratio [HR], 3.523; 95% confidence interval [CI], 2.101-5.907), followed by pulmonary heart disease and diseases of the pulmonary circulation (HR, 2.954; 95% CI, 1.360-6.420).

CONCLUSION: Our findings suggest an association between COVID-19 and mental and behavioral disorders.},
}

@article {pmid41564976,
year = {2026},
author = {Karaviti, D and Charakida, M and Dimopoulou, D and Marmarinos, A and Papadaki, M and Maritsi, D and Spyridis, N and Avgeris, M and Gourgiotis, D and Syggelou, A and Tsolia, M},
title = {Long term cardiovascular effects on COVID-19 infection in children. The need for monitoring.},
journal = {International journal of cardiology},
volume = {},
number = {},
pages = {134188},
doi = {10.1016/j.ijcard.2026.134188},
pmid = {41564976},
issn = {1874-1754},
abstract = {BACKGROUND: Although SARS-CoV-2 infection has been associated with mild illness in children, concerns have emerged regarding potential long-term cardiovascular and systemic effects, even in previously healthy pediatric populations.

OBJECTIVE: The aim of this study is to assess cardiac function and long-term symptoms in children up to one year after COVID-19 infection, and to compare these findings with healthy controls without prior SARS-CoV-2 exposure.

METHODS: In this prospective case-control study, children aged 4-17 years were divided into two groups: those with a confirmed history of COVID-19 (Group 1) and healthy controls (Group 2). Participants underwent echocardiographic evaluation-including global longitudinal strain (GLS) analysis and biochemical testing, including lipid profile and intracellular adhesion molecule -1 (ICAM-1) measurements. A structured symptom survey was used to assess cardiovascular and systemic long-COVID manifestations.

RESULTS: Conventional echocardiographic indices did not differ significantly between groups. However, Group 1 showed a persistent reduction in left ventricular GLS, indicating subclinical myocardial dysfunction (p < 0.05). Long-COVID symptoms were reported in 23.6% of children in Group 1, with fatigue being the most common (16.6%), followed by palpitations (2.0%). Lipid profiles were similar between groups, although children with moderate to severe infections exhibited significantly elevated serum intracellular adhesion molecule-1 (sICAM-1) levels, suggestive of endothelial activation.

CONCLUSION: Even in the absence of overt cardiovascular disease, children with prior SARS-CoV-2 infection experience persistent subclinical cardiac changes and symptoms consistent with Long-COVID. These findings highlight the need for ongoing surveillance and comprehensive cardiovascular assessments in pediatric populations following COVID-19 infection.},
}

@article {pmid41564615,
year = {2026},
author = {Chishtie, FA and Drozd, J and Li, X and Benterki, A and Valluri, SR},
title = {A robust compartmental modeling framework for infectious disease monitoring and analysis via fractional differential equations.},
journal = {Epidemics},
volume = {54},
number = {},
pages = {100887},
doi = {10.1016/j.epidem.2026.100887},
pmid = {41564615},
issn = {1878-0067},
abstract = {This study presents a comprehensive framework for infectious disease monitoring using fractional differential equations, specifically developing the SEIQRDP (Susceptible, Exposed, Infected, Quarantined, Recovered, Deceased, Protected) model. Traditional compartmental models are extended by incorporating fractional calculus, with orders α∈(0,2], which provides enhanced flexibility in capturing memory effects and non-local behaviors inherent in disease transmission dynamics. The framework demonstrates improved accuracy when fitted to Canadian COVID-19 data compared to classical integer-order models, with Wave 1 achieving 22.1% improvement (95% CI: 17.4-26.8%) and Wave 2 achieving 6.2% improvement (95% CI: 3.1-9.3%) in predictive accuracy (average ∼14%). Fractional orders both below and above unity yield superior fits to empirical data depending on epidemic phase, successfully capturing multi-wave dynamics across different pandemic phases. The model incorporates time-dependent parameters to account for varying intervention strategies. Rigorous mathematical analysis including existence, uniqueness, and stability of solutions is provided alongside comprehensive sensitivity analysis. Out-of-sample validation using rolling-origin cross-validation demonstrates robust forecasting performance across 7-, 14-, and 21-day horizons. This research provides public health authorities with an evidence-based tool for epidemic modeling, with proposed extensions for AI-enhanced surveillance, interoperability standards, and Long COVID monitoring discussed as future research directions.},
}

@article {pmid41563438,
year = {2026},
author = {Oliver-Mas, S and Matias-Guiu, JA and Delgado-Alonso, C and Valles-Salgado, M and Gil-Moreno, MJ and López-Carbonero, JI and Fernández-Romero, L and Cuevas, C and Delgado-Álvarez, A and Matias-Guiu, J and Diez-Cirarda, M},
title = {Episodic memory deficits and processes in post-COVID condition.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41563438},
issn = {1433-8491},
support = {INT20/00079//Instituto de Salud Carlos III/ ; FI20/000145//Instituto de Salud Carlos III/ ; CD22/00043//Instituto de Salud Carlos III/ ; CM23/00094//Instituto de Salud Carlos III/ ; G63-HEALTHSTARPLUS-HSP4//Fundación para el Conocimiento madri+d/ ; },
abstract = {Cognitive dysfunction is one of the most prevalent symptoms in patients with post-COVID condition (PCC) and episodic memory has been highlighted as one of the most impaired cognitive domains in these patients. However, few studies have specifically assessed episodic memory processes in these patients. This study aims to comprehensively investigate the memory function in patients with PCC. We conducted a cross-sectional study involving 157 patients with PCC and 74 healthy controls. Participants underwent a comprehensive neuropsychological assessment and memory assessment, including the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), the Free and Cued Selective Reminding test (FCSRT), the Open-Trial Selective Reminding Test (OT-SRT), and a Mental Ability Questionnaire (FLEI). We compared groups and evaluated the correlation between episodic memory and neuropsychological and clinical assessments. Patients with PCC showed reduced performance on the LASSI-L, the FCSRT and the OT-SRT compared to controls. The memory scores showed positive moderate correlations with attention tests and positive low correlations with language, visuospatial or executive functions. Subjective memory complaints were related to poorer memory performance. LASSI-L was the test most associated with subjective memory complaints, whereas OT-SRT was the test less influenced by attention tests. The study found multiple memory processes impaired in patients with PCC, specifically in initial encoding, learning information acquisition and storage, and in retrieval, with only partial improvement with cues and recognition, and with significant susceptibility to the effects of retroactive semantic interference. These findings are relevant for characterising the cognitive deficits of patients with PCC and for designing interventional strategies.},
}

@article {pmid41562619,
year = {2026},
author = {Tien, C-F and Lin, E-J and Tsai, W-H and Tsai, W-T and Chen, M-Y and Su, Y-S and Wu, H-C and Chiu, Y-T and Tung, W-J and Kuo, Y-P and Su, Y-W and Chen, H-W and Chen, F-J and Chuang, T-H and Wang, H-T and Yu, G-Y},
title = {SARS-CoV-2 spike protein expression drives post-acute coagulopathy.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0125525},
doi = {10.1128/jvi.01255-25},
pmid = {41562619},
issn = {1098-5514},
abstract = {During the COVID-19 pandemic, multiple SARS-CoV-2 variants emerged, each with distinct pathogenicity and transmissibility. This study investigated the role of the viral spike (S) protein in disease progression, focusing on the highly virulent S variant. The Delta S protein exhibited enhanced cleavage efficiency at the S1/S2 junction, resulting in partial dissociation of the S1 subunit, with detectable levels of extracellular S1. Unexpectedly, transient expression of Ancestral and Delta S protein induced by a recombinant vesicular stomatitis viral vector caused mild pulmonary inflammation, neutrophil activation, microthrombosis, and ~40% mortality in transgenic K18-hACE2 mice between 8 and 16 days, similar to post-COVID sequelae. The diseased mice displayed splenic atrophy and systemic inflammation, with elevated serum IGFBP-1 and CXCL13 levels. Consistent with the animal findings, serum samples from long COVID patients showed significantly elevated IGFBP-1 levels. CXCL13 levels were particularly elevated in patients with more severe long COVID symptoms. Notably, treatment with the antiplatelet agent aspirin significantly reduced both mortality and weight loss in mice exposed to Delta S protein expression. These findings suggest that SARS-CoV-2 S protein-associated coagulation and systemic inflammation during infection may contribute to the development of post-acute sequelae of COVID-19.IMPORTANCEOur study investigates the distinctive pathogenic properties of the SARS-CoV-2 spike (S) protein from highly virulent variants, with a particular focus on its delayed pathological effects in mice. Using a vesicular stomatitis virus (VSV) vector to transiently express the Ancestral and Delta variant S proteins in K18-hACE2 mice, we observed minimal acute symptoms initially; however, approximately 40% of the mice developed mild pulmonary inflammation, neutrophil activation, and microthrombosis, leading to death between 8 and 16 days post-infection. This delayed pathology was accompanied by elevated circulating levels of CXCL13 and IGFBP-1. Consistent with these findings, serum samples from long COVID patients also showed significantly increased IGFBP-1 levels, while CXCL13 levels were particularly elevated in individuals with more severe long COVID symptoms. These findings provide important observational evidence that may guide future mechanistic studies on long COVID and inform the development of potential therapeutic approaches.},
}

@article {pmid41562079,
year = {2025},
author = {Pridgen, WL and Putrino, D},
title = {Patient-reported improvements from use of IMC-2 alone and IMC-2 and Paxlovid[®] in a Long COVID cohort: a case series.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1698271},
pmid = {41562079},
issn = {1664-3224},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Antiviral Agents/therapeutic use/administration & dosage ; Aged ; *SARS-CoV-2/drug effects ; *COVID-19/virology ; *COVID-19 Drug Treatment ; Adult ; Patient Reported Outcome Measures ; Drug Therapy, Combination ; Treatment Outcome ; },
abstract = {INTRODUCTION: Long COVID (LC) is an infection-associated chronic condition and illness (IACCI) with no currently approved treatments. In order to address SARS-CoV-2 persistence and herpesvirus reactivation, which have been implicated as drivers of LC, sustained use of antiviral combinations may be useful in treating patients with the illness.

METHODS: A convenience sample of patients undergoing an extended course of antiviral therapy was studied. Patients received either 120 days of IMC-2 only (IO) or 120 days of IMC-2 with the addition of 15 days of Paxlovid (IP), prescribed off-label at an outpatient clinic for people with LC. The Patient Global Impression of Change (PGIC) was used to measure therapy response over time, with primary focus on fatigue and secondary focus on brain fog and dysautonomia. Visual analog scales (VAS) were also used to track perceived symptom improvements.

RESULTS: A total of 27 people with LC were approached for treatment, of whom 24 completed one or both protocols. Twelve received the IO protocol, and 12 received the continuous IP combination. Both groups reported reductions in fatigue on the PGIC, but participants receiving IP experienced a statistically significant improvement compared with those receiving IO (p < 0.0001). Similarly, using a VAS, patients in the IP group reported an average 55.3% (p < 0.0001) greater reduction in fatigue than the IO group. Participants who completed the IP intervention demonstrated durable clinical benefit, with symptom improvements remaining consistent at 120-, 305-, and 731-day follow-ups.

DISCUSSION: This small, open-label case series provides pilot evidence supporting the need for a larger trial of combination antivirals for people living with LC. Based on these results, a larger, controlled trial of IMC-2 paired with Paxlovid is recommended.},
}

Humans
Male
Female
Middle Aged
*Antiviral Agents/therapeutic use/administration & dosage
Aged
*SARS-CoV-2/drug effects
*COVID-19/virology
*COVID-19 Drug Treatment
Adult
Patient Reported Outcome Measures
Drug Therapy, Combination
Treatment Outcome

@article {pmid41561147,
year = {2026},
author = {Kröpfl, JM and Hauser, C and Beugger, L and Hanssen, H and Schwendinger, F and Schmidt-Trucksäss, A},
title = {Circulating angiogenic progenitor cell apoptosis in Post-COVID-19 syndrome.},
journal = {International journal of cardiology. Heart & vasculature},
volume = {62},
number = {},
pages = {101866},
pmid = {41561147},
issn = {2352-9067},
abstract = {BACKGROUND: Cellular endothelial dysfunction in patients recovering from Coronavirus disease 2019 (COVID-19) remains poorly understood. This study examined circulating angiogenic progenitor cells (CAC) and mature endothelial cells (CEC) in individuals with persistent symptoms following hospitalization for COVID-19 (PH-PCS) at ≥ 18-months post-infection.

METHODS: We compared PH-PCS (n = 14) to matched controls without symptomatic COVID-19 (n = 7). Examinations included macro- and microvascular structure and function and the analysis of CAC and CEC using flow cytometry.

RESULTS: Estimates indicated somewhat lower apoptotic CAC concentrations (mean difference[md] [95 %CI] = 0.050 cells/µl [0.003, 0.137], p = 0.084) and proportions (% total CAC, 7.7 percentage points (pp) [0.3, 12.9], p = 0.066) in patients compared to controls, though estimates were imprecise. Similar results were observed for apoptotic CEC concentrations (1.202 cells/µl [0.040, 7.518], p = 0.066) and proportions (% total CEC, 2.7 pp [0.2, 23.8], p = 0.048). Live CAC (-7.6 pp [-12.7, -1.1], p = 0.084) and live CEC proportions (-4.9 pp [-23.7, -0.3], p = 0.042) were somewhat enhanced in PH-PCS. Brachial-arterial flow-mediated dilation (baFMD) and retinal vessel imaging parameters showed little evidence for differences between groups, except for maximal arteriolar constriction, where estimates suggested on average higher values in PH-PCS (md [95 %CI] = 1.64 [0.050, 3.63], p = 0.084), but estimates were uncertain. Pooling PH-PCS and controls, correlations were observed between reduced baFMD and both elevated total CEC concentrations (ρ = -0.56, p = 0.038) and decreased apoptotic CAC proportions (ρ = 0.56, p = 0.042).

CONCLUSIONS: This study suggests the possibility of unbalanced CAC and CEC apoptosis in PH-PCS, but with uncertain magnitude. The findings might inform hypothesis generation for future studies on (cellular) endothelial function in PH-PCS.},
}

@article {pmid41559790,
year = {2026},
author = {García-Hidalgo, MC and Mota-Martorell, N and González, J and Benítez, ID and Company-Marín, I and Jové, M and Barbé, F and Amigó, N and Pamplona, R and de Gonzalo-Calvo, D and Torres, G},
title = {Multilayer metabolomic integration reveals bioenergetic disruption in Long COVID.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07684-3},
pmid = {41559790},
issn = {1479-5876},
}

@article {pmid41559785,
year = {2026},
author = {Inderyas, M and Thapaliya, K and Marshall-Gradisnik, S and Barnden, L},
title = {Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07708-y},
pmid = {41559785},
issn = {1479-5876},
}

@article {pmid41559736,
year = {2026},
author = {Kontou, K and Daynes, E and Singh, SJ and Evans, RA and Gardiner, N and Chaplin, E and Richardson, M and Bishop, N and Creese, J and Bateman, N and Wright, A and Zivtins, E and Houchen-Wolloff, L},
title = {The effectiveness and acceptability of face-to-face rehabilitation for patients with Long Covid who were not hospitalised with their acute infection: a mixed-methods study comprising a randomised controlled trial (RCT) with embedded qualitative component.},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-025-09419-z},
pmid = {41559736},
issn = {1745-6215},
support = {223512/Z/21/Z/WT_/Wellcome Trust/United Kingdom ; },
abstract = {BACKGROUND: Long Covid is a term used to describe a multisystem condition that presents with a myriad of physical and psychological symptoms that continue or develop after acute COVID-19. Long Covid is a significant public health problem because of the nature of the illness, its negative impfact on everyday functioning, and the healthcare inequalities evident in access and experience, notably in terms of ethnicity and socioeconomic status. Evidence in patients hospitalised with their acute infection suggests exercise-based rehabilitation could be helpful to improve exercise tolerance, respiratory symptoms, fatigue, and cognition; however, research is needed to determine whether exercise-based rehabilitation is effective and acceptable for patients with Long Covid who were not hospitalised.

METHODS: This mixed-methods study comprises a single-centre, randomised controlled trial to determine whether face-to-face rehabilitation increases exercise capacity compared to usual care alone in non-hospitalised patients with Long Covid, with embedded qualitative components to explore intervention acceptability in the context of healthcare inequalities. Usual care is as defined by the National Institute for Clinical Excellence (NICE) Covid-19 guidance. The rehabilitation intervention will take place twice a week for 6 weeks and will combine symptom-titrated exercise with self-management education. The proposed sample size of 56 for the randomised controlled trial is calculated on the primary outcome of Incremental Shuttle Walking Test (ISWT) distance, with a change of 50metres (m) at 90% power, a standard deviation of 17 m, and a 0.05 type 1 error.

DISCUSSION: A mixed-methods approach has been chosen as quantitative data alone would be insufficient to answer the research question, and mixing the data will enable a more comprehensive understanding and ensure there is an equal focus on outcomes and experiences of a face-to-face exercise-based rehabilitation programme. A healthcare inequalities lens will explore who may be under-represented, with the qualitative work providing further evidence as to why this may be the case. It is recognised that meeting recruitment targets in the context of reducing referral rates and funding for Long Covid services may prove challenging.

TRIAL REGISTRATION: ISRCTN trial registry (ISRCTN33340595). Registered on 30 September 2024.},
}

@article {pmid41559316,
year = {2026},
author = {Shi, Y and Li, B and Zheng, Y and Xue, C and Zhu, J},
title = {Therapeutic effect of anti-neuroinflammatory supplement combined with olfactory training on post-covid olfactory dysfunction: a systematic review and meta-analysis.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {},
number = {},
pages = {},
pmid = {41559316},
issn = {1434-4726},
abstract = {BACKGROUND: There is no established specific treatment for post-COVID olfactory dysfunction (PCOD) currently. Olfactory training (OT) is the only effective intervention supported by clinical evidence. The anti-neuroinflammatory supplement palmitoylethanolamide and luteolin (PEA-LUT) has shown potential in alleviating the symptoms of post-COVID, but its therapeutic effect on olfactory dysfunction and the gain effect when combined with OT remain to be evaluated.

METHODS: We comprehensively searched the online databases EMBASE, PubMed, ScienceDirect, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrials.govfor the literature related to the treatment of PCOD, identified studies reporting the efficacy of PEA-LUT combined with OT, extracted the treatment outcome data, and performed data synthesis.

RESULTS: A total of 7 eligible RCTs published between 2021 and 2024 were included, comprising 525 patients with PCOD. Of the seven studies, five (71.4%) used the full Threshold-Discrimination-Identification (TDI) scoresystem to assess olfactory function, while two (28.6%) used only the Identification ("I") subscale; 332 patients (63.2%) received PEA-LUT + OT therapy and 203 (38.8%) received OT alone. Meta-analysis of these studies showed that patients receiving PEA-LUT combined with OT had significantly higher TDI scores compared to those receiving OT alone (Standard mean difference (SMD) = 0.90; 95% CI: 0.24-1.58; P < 0.01). The overall response rate was also significantly higher in the combination group (Risk difference (RD) = 0.33; 95% CI: 0.01-0.64; P = 0.04).

CONCLUSION: The neuroprotective properties of PEA-LUT appear to enhance recovery from post-COVID olfactory dysfunction. When combined with olfactory training, this treatment shows promising potential as a novel therapeutic approach.},
}

@article {pmid41558579,
year = {2026},
author = {Chen, G and Zhou, S and Chen, Y and Zhou, J and Wang, N and Feng, Y},
title = {OLink proteomic biomarker to predict clinical efficacy of Macaranga sinensis Müll.Arg: A nested case-control study.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121243},
doi = {10.1016/j.jep.2026.121243},
pmid = {41558579},
issn = {1872-7573},
abstract = {Despite the fact that herbal medicine has been used for a long time, their clinical application is challenged by unclear active ingredients and poorly understood mechanisms of action, resulting in considerable heterogeneity in therapeutic outcomes among patients.

AIM OF THE STUDY: To explore the use of OLink-based biomarkers to predict the efficacy of Macaranga sinensis Müll.Arg in individuals with long COVID-related fatigue.

MATERIALS AND METHODS: This nested case-control study recruited long COVID participants who had routinely taken Macaranga sinensis Müll.Arg for more than three months. Case (response) and control (non-response) group were defined based on the change in Brief Fatigue Inventory (BFI) score. Plasma samples were analyzed using OLink. Mann-Whitney U test, Lasso and Ridge regression model, Random Forest, and Support Vector Machine (SVM) were used for differential expression analysis, feature selection, and biomarker identification, respectively.

RESULTS: A total of 55 long COVID fatigue patients was included in this study (27 in case group and 28 in control group). Differential expression analysis filtered in a total of 13 potential biomarkers (log2 fold change > 0.5; p < 0.05). Feature selection further selected 11 biomarkers, including uPA, TRAIL, IL-10, IL-18R1, CX3CL1, EPHB4, COL1A1, Flt3L, EGFR, IL-1RT2, and IFN-γ (all p < 1e-6). Random Forest and SVM identified the key biomarker of CX3CL1 (F1-score of 0.72).

CONCLUSIONS: Our exploratory analysis suggests that CX3CL1 is the candidate biomarker for predicting the efficacy of Macaranga sinensis Müll.Arg, warranting further investigation in larger studies. Our work highlights the translational potential of integrating statistical modeling and machine learning approaches with proteomic data to identify predictive biomarkers for herbal medicine efficacy in clinical settings.},
}

@article {pmid41557618,
year = {2026},
author = {Rohner, S and Schnepper, R and Meienberg, A and Bopp, K and Mayr, M and Meinlschmidt, G and Schaefert, R},
title = {Protocol of the digital long COVID study: A single-center, registry-based, feasibility and clinical evaluation study to investigate a 12-week digital intervention program for people affected by post-COVID-19 condition.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0340385},
doi = {10.1371/journal.pone.0340385},
pmid = {41557618},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/complications/therapy ; Feasibility Studies ; Registries ; SARS-CoV-2/isolation & purification ; Telemedicine ; Male ; Female ; },
abstract = {Up to 400 million individuals globally are estimated to experience persistent symptoms, including fatigue, muscle pain, and brain fog, following severe acute respiratory syndrome coronavirus type 2 infection. These persistent symptoms are referred to as Post-COVID-19 condition if they last for more than 12 weeks after infection and persist for at least 8 weeks and often causing significant distress and burden. The underlying pathological mechanisms have not yet been fully elucidated. Due to the heterogeneity of the disease a multifactorial origin is highly likely. Overall, evidence on optimal management is limited, and no medication has yet proven to be effective. Current symptom management and treatment guidelines suggest a biopsychosocial perspective and emphasize multidisciplinary approaches. Comprehensive interventions, adequate treatment access, and appropriate resources remain insufficiently available and implementing digital interventions might help mitigate these limitations. This protocol details a single-site feasibility and clinical evaluation study aiming to bridge this gap. By implementing an exploratory, open-label, digital interventional approach this study investigates the feasibility and efficacy of a 12-week program delivered by a cloud-based application. The program consists of 13 modules encompassing a wide range of topics (e.g., energy management, self-care, stress management) and includes informational (e.g., psychoeducational content) and interactive (e.g., exercises, self-reflection diaries) components. Customization options align the material with participant needs. A dedicated feedback section in each module captures feedback regarding usability and feasibility. Participants are monitored and checked for adherence throughout the study. The primary outcome is the post-intervention change in functional capacity measured by the World Health Organization Disability Assessment Schedule 2.0. All participants provide written informed consent. Key results from the study will be published in peer-reviewed journals.},
}

Humans
*COVID-19/complications/therapy
Feasibility Studies
Registries
SARS-CoV-2/isolation & purification
Telemedicine
Male
Female

@article {pmid41552054,
year = {2025},
author = {Virno, T and Tomilonus, N and Hart, J and Van Rensburg, C and Walsh, D},
title = {COVID-19-Associated Cystitis: De Novo Urinary Urgency Following SARS-CoV-2.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99386},
pmid = {41552054},
issn = {2168-8184},
abstract = {COVID-19 is widely recognized as a systemic disease with pulmonary, cardiovascular, and neurologic manifestations, yet growing evidence highlights the genitourinary tract as another important site of involvement. A distinct clinical entity, COVID-associated-cystitis (CAC), has been described in which patients develop de novo or worsening lower urinary tract symptoms (LUTS), such as urgency, frequency, and nocturia, without bacterial infection. This case report describes a 71-year-old woman who developed persistent urinary urgency following recovery from COVID-19, successfully treated with oxybutynin. The case is contextualized within the expanding literature on CAC, including evidence from biomarker studies, mechanistic analyses, and large cohort investigations. Emerging data support a pathophysiologic role for both inflammatory cytokine release and viral receptor expression in the bladder, with symptom overlap between CAC, overactive bladder (OAB), and interstitial cystitis. Recognition of CAC is clinically significant, preventing misdiagnosis as bacterial cystitis and guiding management using established OAB frameworks. The case underscores the importance of considering genitourinary sequelae of COVID-19 and contributes to the growing discussion on long COVID and bladder health.},
}

@article {pmid41551009,
year = {2025},
author = {Wang, B and Wang, Y and Ning, K},
title = {Unveiling the role of the respiratory microbiome in long COVID pathogenesis and therapeutics.},
journal = {Chinese medical journal pulmonary and critical care medicine},
volume = {3},
number = {4},
pages = {221-224},
pmid = {41551009},
issn = {2772-5588},
}

@article {pmid41550084,
year = {2026},
author = {Slack, IF and O'Shea, KM and Freigeh, GE and Franco, LM and Jaafar, S and Schuler, CF and Baker, JR},
title = {COVID-19 mRNA revaccination is safe and well tolerated in individuals with previous adverse reactions to the vaccine and/or long COVID.},
journal = {The journal of allergy and clinical immunology. Global},
volume = {5},
number = {2},
pages = {100620},
pmid = {41550084},
issn = {2772-8293},
abstract = {BACKGROUND: Vaccine safety is a primary concern among those with a history of adverse reactions to coronavirus disease 2019 (COVID-19) mRNA vaccines. Retrospective data and cohorts of individuals with severe previous reactions suggest that revaccination is safe and well tolerated. However, prospective data are limited.

OBJECTIVE: We sought to prospectively assess safety and tolerability of COVID-19 mRNA vaccines in individuals with a history of adverse vaccine reactions and in individuals with long COVID.

METHODS: Adults with a self-reported adverse reaction to COVID-19 mRNA vaccination and/or long COVID underwent COVID-19 mRNA revaccination at the University of Michigan with 30-minute observations. Participants were contacted by telephone after 7 days to review interval adverse events.

RESULTS: A total of 103 participants received COVID-19 mRNA revaccination-91 with history of adverse vaccine reaction, 20 with long COVID, and 8 with both. Mean age at enrollment was 41.8 years, and women were 67% of the cohort. Five individuals (4.9%) developed immediate symptoms with revaccination. All 5 events were mild (Consortium for Food Allergy Research severity level 1). Vital signs were assessed prevaccination and 30 minutes postvaccination. At 7-day follow-up, 77% of participants reported at least 1 adverse event, with fatigue (33.7%), headache (29.7%), and muscle pain (28.7%) most commonly reported. No follow-up reactions were severe. Five of the 103 participants had incidentally elevated baseline serum tryptase. None of these participants experienced immediate symptoms with revaccination.

CONCLUSIONS: Revaccination with COVID-19 mRNA vaccines was safe and well tolerated among individuals with previous adverse COVID-19 mRNA vaccine reaction and/or long COVID.},
}

@article {pmid41548411,
year = {2026},
author = {Richard, L and Nisenbaum, R and Dyer, A and Mergarten, D and Brown, M and Stewart, S and Hwang, SW},
title = {Identifying potential post-COVID-19 condition among people experiencing homelessness using longitudinal symptom patterns: A prospective cohort study.},
journal = {Public health},
volume = {252},
number = {},
pages = {106148},
doi = {10.1016/j.puhe.2026.106148},
pmid = {41548411},
issn = {1476-5616},
abstract = {OBJECTIVES: People experiencing homelessness have high SARS-CoV-2 infection and re-infection burden, potentially leading to higher prevalence of post-COVID-19 condition (PCC). However, high baseline symptom rates may make identification of PCC difficult or impossible in this population. This study evaluates symptom patterns over time to assess their ability to identify potential PCC among individuals experiencing homelessness.

STUDY DESIGN: Prospective cohort study METHODS: We prospectively followed a large (n = 736), representative cohort of people experiencing homelessness recruited at random from 62 sites in Toronto, Canada between June and September 2021. Participants were interviewed up to five times over approximately 12 months. Longitudinal patterns of twelve self-reported symptoms were assessed through latent transition analysis, and generalized estimating equations with logit link were applied to determine their association with known risk of potential PCC.

RESULTS: Among 736 participants, three latent statuses were identified: (1) 'No/Few Symptoms' (≥70 %), (2) 'Non-Specific Symptoms' (15-23 %), and (3) 'Infection-Related Symptoms' (≤5 %). Statuses 2 and 3 were associated with being at risk of PCC following symptomatic infection (aOR 3.41 [95 % CI 2.3-5.0] and 3.18 [95 % CI 1.6-6.4]) but not with being at risk of PCC overall. Transition probabilities suggested PCC would mostly occur among individuals with symptoms at baseline. However, the clustered area under the curve was modest (0.70 [95 % CI 0.65-0.75]), indicating symptom-based approaches are suboptimal for identification of potential PCC.

CONCLUSIONS: Self-reported symptoms do not reliably identify potential PCC among people experiencing homelessness, due to high rates of underlying symptoms and asymptomatic infections. Alternative, strengths-based approaches are recommended to more equitably identify post-COVID condition in this population.},
}

@article {pmid41547213,
year = {2026},
author = {Carrascosa Gil, A and Gabella Martín, M and Salazar Lozano, MDC and Tamayo Gómez, E and Rico Feijoo, J and Álvarez de Santullano, CA},
title = {[Long-term symptomatic follow-up of patients with Long COVID syndrome].},
journal = {Atencion primaria},
volume = {58},
number = {3},
pages = {103425},
doi = {10.1016/j.aprim.2025.103425},
pmid = {41547213},
issn = {1578-1275},
abstract = {OBJECTIVE: The primary aim of the study was to investigate the long-term symptom progression of long COVID. The secondary objective was to assess whether any treatment had an impact on symptom evolution.

DESIGN: Longitudinal, prospective, observational, uncontrolled study.

SETTING: Internal Medicine Department, Río Hortega University Hospital (Valladolid).

PARTICIPANTS: 40 patients with long COVID (cases) and 40 volunteers (controls) of the same age and sex as the cases, who had experienced acute COVID-19 without developing long COVID.

MAIN MEASUREMENTS: Scales, indices, and questionnaires were sent by post to evaluate the main symptoms of long COVID. The following were assessed: fatigue (MFIS), emotional disorders (HADS), sleep disturbances (PSQI), cognitive impairments (MFE-30), dyspnea (mMRC), physical exercise (GPAQ), quality of life (SF-36), and pain (CPGS). The cases were reassessed after three years.

RESULTS: After three years, cases showed an improvement in dyspnea (mMRC), which decreased from 1.38 to 1.10 (p=0.014). Ten cases reported having followed aerobic and/or anaerobic physical exercise as treatment, and it was observed that their pain severity (CPGS) improved from 2.7 to 1.3 (p=0.039). In the remaining measurements, variations among cases did not reach statistical significance.

CONCLUSIONS: After three years of follow-up, patients with long COVID continued to have similar symptom scores to their initial assessments, and worse than those of the control group. Aerobic and/or anaerobic physical exercise may contribute to partially improving symptom evolution. .},
}

@article {pmid41543809,
year = {2026},
author = {Bozkir, C and Kartal, T and Hokelek, B},
title = {Obesity and Nutritional Vulnerability in long COVID: A Neuroinflammatory and Cognitive Perspective.},
journal = {Current nutrition reports},
volume = {15},
number = {1},
pages = {5},
pmid = {41543809},
issn = {2161-3311},
mesh = {Humans ; *Obesity/complications/physiopathology ; *COVID-19/complications ; *Nutritional Status ; *Neuroinflammatory Diseases ; SARS-CoV-2 ; Malnutrition/complications ; Cognition ; Inflammation ; Cognitive Dysfunction/etiology ; },
abstract = {PURPOSE OF REVIEW: To examine the interplay between obesity, nutritional vulnerability, and long COVID, with a particular focus on neuroinflammatory and cognitive outcomes. This review synthesizes emerging evidence on shared pathophysiological pathways and evaluates the therapeutic potential of dietary and weight management strategies.

RECENT FINDINGS: Cognitive symptoms such as brain fog and memory deficits are among the most persistent and disabling features of long COVID. Obesity is associated with more severe manifestations through pathways involving chronic systemic inflammation, compromised blood-brain barrier integrity, and neuroimmune dysregulation. Concurrently, malnutrition and poor diet quality including low intake of antioxidants, omega-3 fatty acids, and micronutrients may impair neuroplasticity and delay recovery. Interventions such as Mediterranean and ketogenic dietary patterns, as well as structured weight loss programs, show promise in reducing inflammation and improving cognitive outcomes. Obesity and suboptimal nutritional status amplify the neurocognitive burden of long COVID through shared pathophysiological mechanisms. Integrated care models that incorporate metabolic screening, nutritional assessment, and individualized dietary interventions may improve recovery trajectories. Public health strategies that address food quality, obesity prevention, and equitable access to nutrition care are essential for long-term resilience in the post-COVID era.},
}

Humans
*Obesity/complications/physiopathology
*COVID-19/complications
*Nutritional Status
*Neuroinflammatory Diseases
SARS-CoV-2
Malnutrition/complications
Cognition
Inflammation
Cognitive Dysfunction/etiology

@article {pmid41542038,
year = {2026},
author = {Rehman, J and Kwissa, M and Mathayan, M and Salunkhe, S and Bakthavachalam, V and Ye, Z and Sanborn, M and Condo, S and Upadhye, A and Nemakal, A and Wang, H and Chan, J and Richner, J and Basu, S and Novak, R and Jacobson, J and Ganesh, B and Cerda, M and Brim, H and Erdmann, N and Levy, B and Marshall, G and McComsey, G and Metz, T and Okumura, M and Peluso, M and Walker, T and Utz, P and Krishnan, J and Prabhakar, B},
title = {Persistent Immune Dysregulation during Long COVID is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8302624/v1},
pmid = {41542038},
issn = {2693-5015},
abstract = {Long COVID (LC) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of LC, but the extent of LC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed LC. Compared to convalescent, LC participants with a broad range of LC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the LC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa- associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in LC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in LC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity.},
}

@article {pmid41541965,
year = {2025},
author = {Zhang, L and Li, L and Chen, J and Pang, S and Zhang, Z and Yan, Y},
title = {Psychological Burden of Long COVID and Associated Factors Among Nurses Two Years Post-infection: A Cross-Sectional Study.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99231},
pmid = {41541965},
issn = {2168-8184},
abstract = {BACKGROUND: The COVID-19 pandemic has generated sustained physical and psychological impacts on healthcare workers. Growing evidence suggests that some individuals develop persistent multisystem manifestations long after the acute phase, collectively referred to as long COVID. Nurses, who have borne heavy workloads and ongoing psychological stress since the pandemic, may be particularly vulnerable; however, limited research has examined their mental health status two years after infection.

AIMS: This study aimed to evaluate anxiety and depression levels among nurses two years after COVID-19 infection, compare psychological characteristics across clinical departments, and identify factors associated with long COVID.

METHODS: A cross-sectional online survey was conducted among nurses at a tertiary hospital, yielding 735 valid responses. Data were collected using a general information questionnaire, the Generalized Anxiety Disorder-7 (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9). Participants were categorized into long COVID (n = 263) and non-long COVID (n = 472) groups. Between-group differences were examined using appropriate parametric or non-parametric tests, and variables with P < 0.10 were entered into multivariable logistic regression to identify independent predictors.

RESULTS: Nurses with long COVID were significantly older and exhibited higher GAD-7 and PHQ-9 scores than those without long COVID (all P < 0.001). Multivariate analysis showed that higher PHQ-9 scores (odds ratio (OR) = 1.147, 95% confidence interval (CI): 1.108-1.188) and older age (OR = 1.040, 95% CI: 1.011-1.070) were independently associated risk factors for long COVID. Although the prevalence of long COVID did not differ significantly across departments (P = 0.378), anxiety and depression levels varied, with nurses in high-risk exposure departments reporting higher GAD-7 and PHQ-9 scores than those in outpatient and medical-technical departments.

CONCLUSION: Two years after infection, nurses with long COVID continue to experience substantial psychological burden, particularly among older individuals and those with more severe depressive symptoms. Although long COVID was evenly distributed across clinical departments, significant interdepartmental differences in anxiety and depression underscore the influence of work characteristics and environment. Targeted psychological support and ongoing mental health monitoring are warranted to promote recovery and enhance occupational resilience in the post-pandemic era.},
}

@article {pmid41538643,
year = {2026},
author = {Segur, PC and Natarelli, TRP and Fonseca, LMM},
title = {Simulated scenario of nursing consultation for long COVID in primary health care.},
journal = {Revista gaucha de enfermagem},
volume = {46},
number = {},
pages = {e20240376},
doi = {10.1590/1983-1447.2025.20240376.en},
pmid = {41538643},
issn = {1983-1447},
mesh = {Humans ; *COVID-19/nursing ; *Primary Health Care ; *Education, Nursing/methods ; *Patient Simulation ; *Simulation Training ; *Referral and Consultation ; Female ; *Education, Nursing, Baccalaureate/methods ; },
abstract = {OBJECTIVE: To develop a simulated scenario for undergraduate education on nursing consultation in long COVID situations in Primary Health Care.

METHOD: This is an applied methodological study divided into two stages: first, the clinical case was constructed and validated with nurses with experience in Primary Health Care and/or clinical simulation (n=9). Then, the scenario was constructed and validated with a group of judges composed of professors and postgraduate students (n=11). The Content Validity Index was used to analyze the data, with an agreement level of 80%.

RESULTS: The clinical case and the scenario obtained an average Content Validity Index of 0.98 and 0.90, respectively. Only two items presented values below the minimum acceptable, being reformulated and sent for a second round of validation.

CONCLUSION: The simulated scenario on long COVID was developed and validated, demonstrating its potential for use in undergraduate nursing education and for contributing to professional training in Primary Health Care.},
}

Humans
*COVID-19/nursing
*Primary Health Care
*Education, Nursing/methods
*Patient Simulation
*Simulation Training
*Referral and Consultation
Female
*Education, Nursing, Baccalaureate/methods

@article {pmid41537076,
year = {2025},
author = {Singhal, A and Sahoo, D and Patle, A and Patil, S and Lakkireddy, M and Raja, S and Pyati, A and Arora, A and Dhole, S and Sakthivadivel, and Patil, P and Taranikanti, M and John, NA and Ravi, N},
title = {Evaluation of Inflammatory Biomarkers in Post-COVID-19 Arthritis: a Cross-Sectional Study from Telangana, South India.},
journal = {Maedica},
volume = {20},
number = {4},
pages = {701-707},
doi = {10.26574/maedica.2025.20.4.701},
pmid = {41537076},
issn = {1841-9038},
abstract = {BACKGROUND: Long COVID, a post-COVID-19 syndrome, has been linked to various musculoskeletal manifestations, particularly arthritic symptoms. This study aimed to evaluate the inflammatory markers associated with long COVID in patients diagnosed with COVID arthritis.

METHODS: A cross-sectional prospective study was conducted in a tertiary care centre in Telangana, India, involving 139 PCR-confirmed COVID-19 patients diagnosed with arthritis. Eligible participants were COVID-free for one month to six months. Clinical histories, including severity of arthritis symptoms, levels of inflammatory markers (LDH, uric acid, serum ferritin, rheumatoid factor [RF] and CRP) and radiological investigations (radiographs and ultrasound) were recorded and analyzed. Follow-up assessments occurred at six months, with repeated measurements of inflammatory markers for statistical significance.

RESULTS: The predominant clinical presentations included joint aches, restricted movement, swelling, myalgia and fatigue, with 95% of subjects relying on over-the-counter analgesics. Notably, all measured inflammatory markers decreased over the six-month follow-up, with statistically significant reductions being observed in LDH, RF and CRP levels.

CONCLUSION: COVID arthritis is a complication of long COVID that affects both men and women, with persistent elevation of inflammatory biomarkers. While levels decreased during the follow-up period, extended monitoring is necessary to determine the duration required for normalization. Further research is warranted to understand the long-term implications of these findings.},
}

@article {pmid41536833,
year = {2025},
author = {Amput, P and Wongphon, S},
title = {Comparison of physical fitness in youth with post-COVID-19: A study of individuals with and without symptoms.},
journal = {AIMS public health},
volume = {12},
number = {4},
pages = {1026-1034},
doi = {10.3934/publichealth.2025051},
pmid = {41536833},
issn = {2327-8994},
abstract = {This study aims to examine differences in physical fitness among young adults in three distinct groups: individuals with long COVID, those who had recovered from COVID-19 without lingering symptoms, and healthy individuals with no history of infection. A total of 105 participants were equally divided into the three groups (n = 35 each). Evaluations included handgrip strength for upper body strength, handheld dynamometry for quadricep strength, and a six-minute walk test (6MWT) to assess the cardiorespiratory performance. Participants with long COVID demonstrated significantly lower handgrip strengths compared to the control group. Additionally, both post-COVID groups showed reduced 6MWT distances and elevated post-exercise physiological responses, including heart rate, systolic blood pressure, perceived exertion, and leg fatigue, regardless of symptom persistence. These findings indicate that individuals recovering from COVID-19, especially those with persistent symptoms, exhibit measurable declines in muscular and cardiorespiratory fitness, along with heightened physiological stress during physical activity.},
}

@article {pmid41536211,
year = {2026},
author = {Linnhoff, S and Cohen Kadosh, R and Zaehle, T},
title = {EEG-based frontal excitation/inhibition balance as an objective biomarker for cognitive fatigue across multiple sclerosis and Long COVID.},
journal = {Psychological medicine},
volume = {56},
number = {},
pages = {e21},
doi = {10.1017/S0033291725103024},
pmid = {41536211},
issn = {1469-8978},
support = {539530253//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; Male ; Female ; *Multiple Sclerosis/complications/physiopathology ; *COVID-19/complications/physiopathology ; Adult ; Cross-Sectional Studies ; *Electroencephalography ; Middle Aged ; *Fatigue/physiopathology/etiology/diagnosis ; Biomarkers ; },
abstract = {BACKGROUND: Cognitive fatigue is a prevalent and disabling symptom in neurological and post-viral conditions, including multiple sclerosis (MS) and Long COVID. Assessment relies largely on self-report, and no validated objective biomarker exists, limiting reliable diagnosis and treatment monitoring. The aperiodic exponent of the Electroencephalogram (EEG) power spectrum, reflecting the excitation/inhibition (E/I) balance, is a promising candidate biomarker. We examined whether aperiodic exponent values can objectively identify pathological fatigue and assessed their classification accuracy.

METHODS: We conducted a cross-sectional study, including 119 participants: 36 healthy controls, 33 with Long COVID-related fatigue (LCOF), and 50 with MS (23 fatigued and 27 nonfatigued). Resting-state EEGs were analyzed, and associations with fatigue ratings and group differences were assessed. Logistic mixed-effects regression models evaluated classification accuracy for fatigue status.

RESULTS: Lower frontal aperiodic exponents were associated with higher cognitive fatigue across participants. Fatigued individuals, regardless of diagnosis, showed reduced frontal exponent values compared with nonfatigued groups, while no differences emerged in occipital regions. Logistic regression confirmed that frontal exponent values significantly predicted fatigue status, improving classification accuracy beyond age and depression, with good sensitivity and specificity.

CONCLUSIONS: The frontal aperiodic exponent is a regionally specific biomarker of cognitive fatigue across MS and LCOF. Mechanistic interpretation suggests an altered prefrontal E/I balance, which could inform the development of targeted interventions to alleviate cognitive fatigue. It offers a clinically accessible tool to complement self-report, support trial stratification, and enable objective treatment monitoring. Importantly, its presence across distinct disorders highlights its value as a transdiagnostic marker of fatigue.},
}

Humans
Male
Female
*Multiple Sclerosis/complications/physiopathology
*COVID-19/complications/physiopathology
Adult
Cross-Sectional Studies
*Electroencephalography
Middle Aged
*Fatigue/physiopathology/etiology/diagnosis
Biomarkers

@article {pmid41535956,
year = {2026},
author = {Zhang, Y and Al-Hakeim, HK and Al-Jassas, HK and Maes, M},
title = {The NLRP3 inflammasome as a key pathway in the affective and chronic fatigue symptoms of Long COVID.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07703-3},
pmid = {41535956},
issn = {1479-5876},
}

@article {pmid41535626,
year = {2026},
author = {Kumar, S and Li, C and Zhou, L and Zhan, Q and Alaswad, A and Volland, S and Costa, B and Krooss, SA and Klefenz, I and Schmaus, H and Zeuzem, A and von Witzendorff, D and Lickei, H and Pueschel, L and Kraft, ARM and Cornberg, M and Koczulla, AR and Pink, I and Hoeper, MM and Xu, CJ and Häussler, S and Wiestler, M and Netea, MG and Illig, T and Sun, J and Li, Y},
title = {A distinct monocyte transcriptional state links systemic immune dysregulation to pulmonary impairment in long COVID.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {41535626},
issn = {1529-2916},
support = {14-76403-184//Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)/ ; 14-76403-184//Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)/ ; 01EQ2302A, 031L0318A, ZN4257//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 948207//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; AG069264, AI147394, HL170961, AI176171, AG090337//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {The mechanisms driving immune dysregulation in long COVID disease remain elusive. Here we integrated single-cell multiome data, immunological profiling and functional assays to investigate immune alterations across multiple cohorts. A transcriptional state in circulating monocytes (LC-Mo) was enriched in individuals with mild-moderate acute infection and accompanied by persistent elevations of plasma CCL2, CXCL11 and TNF. LC-Mo showed TGFβ and WNT-β-catenin signaling and correlated with fatigue severity. Protein markers of LC-Mo were increased in individuals with pronounced fatigue or dyspnea, and those with severe respiratory symptoms showed higher LC-Mo expression. Epigenetically, LC-Mo exhibited AP-1- and NF-κB1-driven profibrotic programs. LC-Mo-like macrophages in bronchoalveolar lavage samples from individuals with severe respiratory symptoms displayed a profibrotic profile, and individuals with a high LC-Mo transcriptional state showed impaired interferon responses after stimulation. Collectively, our findings define a pathogenic monocyte transcriptional state linking systemic immune dysfunction to persistent long COVID disease, providing mechanistic insights and potential therapeutic targets.},
}

@article {pmid41535625,
year = {2026},
author = {Antar, AAR and Pasetes, EC and Brennon, KMZ and Cox, AL},
title = {Immunologically distinct long COVID after mild acute disease.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {41535625},
issn = {1529-2916},
}

@article {pmid41535076,
year = {2026},
author = {Prashar, J and Hillman, T and Wall, EC and Sarna, A and Mi, E and Bell, R and Sahota, J and Zandi, M and McNamara, P and Livingston, R and Gore, R and Lunken, C and Bax, E and Nyam, R and Rafie Manzelat, AM and Hishmeh, L and Attree, E and Cone, S and Banerjee, A and Heightman, M},
title = {Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis.},
journal = {BMJ open},
volume = {16},
number = {1},
pages = {e103884},
doi = {10.1136/bmjopen-2025-103884},
pmid = {41535076},
issn = {2044-6055},
mesh = {Humans ; Female ; *COVID-19/therapy/complications/epidemiology/physiopathology ; Male ; Middle Aged ; Prospective Studies ; Adult ; Quality of Life ; *Patient Acceptance of Health Care/statistics & numerical data ; SARS-CoV-2 ; Fatigue ; Hospitalization/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Aged ; Return to Work/statistics & numerical data ; },
abstract = {OBJECTIVE: To characterise long-term trajectory of recovery in individuals with long covid.

DESIGN: Prospective cohort.

SETTING: Single-centre, specialist post-COVID service (London, UK).

PARTICIPANTS: Individuals aged ≥18 years with long covid (hospitalised and non-hospitalised) from April 2020 to March 2024.

MAIN OUTCOME MEASURES: Routine, prospectively collected data on symptoms, quality of life (including Fatigue Assessment Scale (FAS) and EuroQol 5 Dimensions (EQ-5D), return to work status and healthcare utilisation (investigations, outpatient and emergency attendances). The primary outcome was recovery by self-reported >75% of 'best health' (EQ-5D Visual Analogue Scale) and was assessed using Cox proportional hazards regression models over 4 years. Linked National Health Service England registry data provided secondary care healthcare utilisation and expenditure.

RESULTS: We included 3590 individuals (63.3% female, 73.5% non-hospitalised, median age 50.0 years, 71.9% with ≥2 doses of COVID-19 vaccination), who were followed up for a median of 136 (0-346) days since first assessment and 502 (251-825) days since symptom onset. At first assessment, 33.2% of employed individuals were unable to work. Dominant symptoms were fatigue (78.7%), breathlessness (68.1%) and brain fog (53.5%). 33.4% of individuals recovered to >75% of best health prior to clinic discharge (recovery occurred median 202 (94-468) days from symptom onset). Vaccinated individuals were more likely to recover faster (pre: HR 2.93 (2.00-4.28) and post: HR 1.34 (1.05-1.71) COVID-19 infection), whereas recovery hazard was inversely associated with FAS (HR 0.37 (0.33-0.42)), myalgia (HR 0.59 (0.45-0.76)) and dysautonomic symptoms (HR 0.46 (0.34-0.62)). There was high secondary care healthcare utilisation (both emergency and outpatient care). Annual inpatient and outpatient expenditure was significantly lower in hospitalised individuals while under the service. When compared with the prereferral period, emergency department attendances were reduced in non-hospitalised patients with long covid, but outpatient costs increased.

CONCLUSIONS: In the largest long covid cohort from a single specialist post-COVID service to date, only one-third of individuals under follow-up achieved satisfactory recovery. Fatigue severity and COVID-19 vaccination at presentation, even after initial COVID-19 infection, was associated with long covid recovery. Ongoing service provision for this and other post-viral conditions is necessary to support care, progress treatment options and provide capacity for future pandemic preparedness. Research and clinical services should emphasise these factors as the strongest predictors of non-recovery.},
}

Humans
Female
*COVID-19/therapy/complications/epidemiology/physiopathology
Male
Middle Aged
Prospective Studies
Adult
Quality of Life
*Patient Acceptance of Health Care/statistics & numerical data
SARS-CoV-2
Fatigue
Hospitalization/statistics & numerical data
Post-Acute COVID-19 Syndrome
Aged
Return to Work/statistics & numerical data

@article {pmid41532626,
year = {2025},
author = {Pechanova, O and Paulis, L},
title = {Nitric Oxide at the Nexus of ACE2 Biology and COVID-19: Implications for Cardiovascular and Neurodegenerative Comorbidities.},
journal = {Physiological research},
volume = {74},
number = {Suppl 2},
pages = {S171-S184},
pmid = {41532626},
issn = {1802-9973},
mesh = {Humans ; *COVID-19/metabolism/epidemiology/virology ; *Angiotensin-Converting Enzyme 2/metabolism ; *Nitric Oxide/metabolism ; *Cardiovascular Diseases/metabolism/epidemiology/virology ; *Neurodegenerative Diseases/metabolism/epidemiology/virology ; SARS-CoV-2 ; Animals ; Comorbidity ; Renin-Angiotensin System/physiology ; },
abstract = {SARS-CoV-2 engages ACE2 for cell entry, perturbing the counter-regulatory ACE2/Ang-(1-7)/Mas axis and shifting the renin angiotensin system toward ACE/Ang II/AT1 signaling, with a concomitant reduction in nitric oxide (NO) bioavailability. NO sits at the crossroads of these pathways, acting both as an antiviral modulator of spike-ACE2 interactions and as a downstream mediator of Mas-dependent endothelial protection. This review summarizes evidence on NO across three layers: (i) viral entry (S nitrosylation of spike/ACE2, protease modulation), (ii) cardiovascular comorbidities (hypertension, obesity, diabetes) where ACE2 downregulation impairs endothelial NO synthase (eNOS)-dependent NO production and promotes thrombosis and microvascular dysfunction, and (iii) neurovascular/ neurodegenerative sequelae, in which renin-angiotensin-aldosterone system (RAAS) dysregulation along with imbalance between protective eNOS/nNOS and inflammatory iNOS fosters blood-brain barrier disruption, microthrombosis, and cognitive impairment. Shared mechanisms - endotheliitis, microvascular dysfunction, and neuroinflammation may explain convergent risks for cardiac injury and cognitive decline in long COVID-19. Putative therapeutic strategies may include restoring physiological NO (via Mas agonism, Ang-(1-7), inhibition of Ang 1-7 degradation and recombinant ACE2), pulmonary-selective inhaled NO, hybrid S nitrosylated agents, and selective attenuation of iNOS/peroxynitrite alongside endothelial support. Targeted modulation - enhancing eNOS/nNOS while constraining iNOS offers a unified framework to mitigate both cardiovascular and neurodegenerative consequences of COVID-19.},
}

Humans
*COVID-19/metabolism/epidemiology/virology
*Angiotensin-Converting Enzyme 2/metabolism
*Nitric Oxide/metabolism
*Cardiovascular Diseases/metabolism/epidemiology/virology
*Neurodegenerative Diseases/metabolism/epidemiology/virology
SARS-CoV-2
Animals
Comorbidity
Renin-Angiotensin System/physiology

@article {pmid41532581,
year = {2026},
author = {Mason, TB and Dolgon-Krutolow, A and Lee, D and Knight, TK and Lee, R and Herzig, SE and Doctor, JN and Meeker, D},
title = {Ecological momentary assessment of physical symptoms among patients with a history of COVID-19 infection: towards understanding long covid and the role of mental health symptoms.},
journal = {Psychology & health},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/08870446.2025.2612038},
pmid = {41532581},
issn = {1476-8321},
abstract = {OBJECTIVE: This project used ecological momentary assessment (EMA) in adults with a previous COVID-19 infection to examine the association of long covid with physical symptoms and the association of contextual factors with physical symptoms among adults with long covid.

METHOD: Adults who had been diagnosed with COVID-19 (N = 121) completed survey questions about COVID-19 history, long covid and mental and physical health followed by 7-days of EMA. During EMA, participants reported on physical symptoms and contextual factors five times across the day.

RESULTS: Multilevel exploratory factor analyses found two within-subjects (i.e. aches/fatigue and respiratory symptoms) and one between-subjects physical symptom factor. Long covid was associated with more real-world aches/fatigue symptoms compared to those without long covid, and effects persisted after controlling for baseline mental health; long covid was unrelated to respiratory symptoms. Greater within-subjects aches/fatigue were concurrently associated with higher negative affect, higher interpersonal problems, and lower positive affect and prospectively associated with greater negative affect and lower positive affect.

CONCLUSION: Findings show that long covid diagnosis predicts real-world ache/fatigue symptoms, and this effect is not explained by baseline mental health. Furthermore, real-world ache/fatigue symptoms are associated with poor momentary psychosocial functioning and predict acute affective disturbance.},
}

@article {pmid41532554,
year = {2026},
author = {Liao, TL and Liu, PY and Chen, YM and Tang, KT and Liu, HJ and Chen, DY},
title = {Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e08695},
doi = {10.1002/advs.202508695},
pmid = {41532554},
issn = {2198-3844},
support = {NSTC 112-2314-B-075A-002-MY3//National Science and Technology Council/ ; TCVGH-1137305C//Taichung Veterans General Hospital/ ; TCVGH-1133902E//Taichung Veterans General Hospital/ ; TCVGH-1143918C//Taichung Veterans General Hospital/ ; },
abstract = {Immunometabolism and neutrophil extracellular traps (NETs) play pivotal roles in the pathogenesis of coronavirus disease 2019 (COVID-19) and its postacute sequelae. However, the upstream regulators that reprogram neutrophil lipid metabolism and trigger excessive NET formation remain largely undefined. This study identifies a transfer RNA-derived fragment, tRF-His-GTG-1, enriched in platelet-derived extracellular vesicles, as a key driver of neutrophil lipophagy dysfunction and inflammation in COVID-19. The use on neutrophils from 60 patients and 20 healthy controls, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamster model, and multiple in vitro assays shows that severe COVID-19 and long COVID are characterized by increased lipid droplet (LD) accumulation and NET release. Mechanistically, tRF-His-GTG-1 activates Toll-like receptor 8 (TLR8)-mammalian target of rapamycin (mTOR) signaling and suppresses RAB7A expression, changes that impair lipophagic flux. This dual pathway impairs lipophagy and promotes NET formation and proinflammatory cytokine secretion. Importantly, ex vivo treatment with a tRF-His-GTG-1 inhibitor restores lipophagy, reduces LD and NET levels, and suppresses interleukin 1beta (IL-1β)/IL-8 production in patient-derived neutrophils. These findings reveal a novel EV-mediated immunometabolic axis linking platelets to neutrophil dysfunction, and position tRF-His-GTG-1 as a promising RNA-based therapeutic target for COVID-19-associated hyperinflammation.},
}

@article {pmid41532066,
year = {2026},
author = {Feng, X and Wang, Y and Li, Y and Long, J and Liu, F and Yang, H},
title = {Application of the humanized mouse model in research into SARS-CoV-2 infection (Review).},
journal = {Medicine international},
volume = {6},
number = {1},
pages = {9},
doi = {10.3892/mi.2025.293},
pmid = {41532066},
issn = {2754-1304},
abstract = {The coronavirus disease 2019 (COVID-19) pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a profound impact on global public health. The complexity of its pathogenic mechanisms and host interactions urgently requires high-fidelity animal models to support research. Humanized mouse models break the species barrier through gene editing and immune reconstitution technologies, providing a key tool to simulate human infection characteristics and pathological processes. A number of studies have reported the application of humanized mouse models in the fields of COVID-19 research, such as SARS-CoV-2 pathogenesis, anti-SARS-CoV-2 drug discovery and vaccine development, etc. The present review aimed to systematically document the latest advances in the application of humanized mouse models based on different construction strategies, such as receptor humanization, immune system humanization and composite humanization. These models have not only elucidated the pathogenicity differences and immune escape mechanisms of SARS-CoV-2 variants, but have also validated the efficacy of broad-spectrum anti-SARS-CoV-2 strategies, including angiotensin-converting enzyme 2-targeted therapies, antibody cocktail regimens and mucosal vaccines. Additionally, humanized mouse models have played a pivotal role in investigating the mechanisms underlying long COVID. By revealing the multi-system pathogenic mechanisms of pulmonary fibrosis, neurodegeneration and intestinal microbiota dysregulation, these models provide a theoretical foundation for the development of targeted intervention strategies.},
}

@article {pmid41531877,
year = {2025},
author = {Finsterer, J},
title = {There is currently no evidence that long-COVID-19 leads to neurodegenerative diseases such as SDAT, amyotrophic lateral sclerosis, or Parkinson's disease.},
journal = {Brain circulation},
volume = {11},
number = {4},
pages = {354-355},
doi = {10.4103/bc.bc_81_25},
pmid = {41531877},
issn = {2455-4626},
}

@article {pmid41530768,
year = {2026},
author = {Bhéreur, A and McDuff, K and Naye, F and Lemay, L and Grenier, AD and O'Hara, ME and Nathanson, J and Lavoie, KL and Sasseville, M and Kadakia, Z and Décary, S and Munblit, D and O'Brien, KK},
title = {Rethinking measurement of health outcomes in Long COVID: complexities, challenges and considerations.},
journal = {Health and quality of life outcomes},
volume = {24},
number = {1},
pages = {8},
pmid = {41530768},
issn = {1477-7525},
}

@article {pmid41529159,
year = {2026},
author = {Berkowitz, J and Lu, F and DeAngelis, J and Simmons, J and Wu, WC},
title = {Comparative Efficacy of Pulmonary Rehabilitation in Patients With COPD, ILD, and Long COVID: PHYSICAL AND PSYCHOSOCIAL OUTCOMES.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {},
number = {},
pages = {},
pmid = {41529159},
issn = {1932-751X},
abstract = {INTRODUCTION: The benefits of pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) are well-established, but data on the relative efficacy of PR in patients with interstitial lung disease (ILD) and prolonged symptoms from coronavirus disease-2019 (Long COVID) remain limited. With the increasing prevalence of Long COVID, understanding the role of PR in this group is essential.

METHODS: Records of patients enrolled in PR between September 1, 2020, to November 30, 2022, at an academic health system were analyzed. Patients were categorized into COPD, ILD, and Long COVID groups based on primary referral diagnosis. Outcome measures included 6-minute walk test distance, COPD Assessment Tool, Modified Medical Research Council Questionnaire, and psychosocial assessments. Mixed-linear modeling for repeated measures compared pre- and post-PR outcomes within and across groups by referral diagnosis while adjusting for baseline covariates.

RESULTS: Of the 316 patients enrolled in PR, 192 completed PR. Demographics were similar across groups, though patients with Long COVID were younger, more likely to be Hispanic, and have higher body mass index than patients referred for COPD. Significant improvements were observed in functional capacity, dyspnea, quality of life, depression, anxiety, and stress in all 3 groups following PR without significant between-group differences in PR outcomes.

DISCUSSION: This single-center analysis suggests that PR was associated with significantly improved physical and psychosocial well-being in patients with COPD, ILD, and Long COVID with comparable outcomes across all groups. Future randomized-controlled trials are needed to confirm the benefits of PR for patients with Long COVID.},
}

@article {pmid41528554,
year = {2026},
author = {Wilkey, HL and Datta, BK},
title = {Family history of cancer as a risk factor for Long COVID among United States adults.},
journal = {Cancer causes & control : CCC},
volume = {37},
number = {1},
pages = {17},
pmid = {41528554},
issn = {1573-7225},
mesh = {Humans ; Female ; *Neoplasms/epidemiology/genetics ; Male ; *COVID-19/epidemiology/virology ; United States/epidemiology ; Middle Aged ; Adult ; Risk Factors ; Cross-Sectional Studies ; Prevalence ; Aged ; SARS-CoV-2 ; Young Adult ; Health Surveys ; },
abstract = {BACKGROUND: Previous research has identified several risk factors for Long COVID, including cancer. This study aims to assess whether adults with a family history of cancer had a higher risk for Long COVID.

METHODS: This cross-sectional study used data on 25,389 adults, who were not cancer patients or survivors, from the nationally representative 2023 National Health Interview Survey. Multivariable generalized linear models were estimated to assess the prevalence of Long COVID (i.e., having symptoms for ≥ 3 months) for self-reported family history of cancer by sequentially adjusting for demographic and socioeconomic attributes, health behaviors, and underlying health conditions. Karlson-Holm-Breen (KHB) method was applied to assess potential mediating effects of health conditions.

RESULTS: Long COVID prevalence in the study population was 8.4%. Adults with a family history of cancer were 1.26 (95% CI 1.15-1.38) times more likely to have Long COVID. The prevalence rate ratio decreased to 1.19 (95% CI 1.08-1.28) when health conditions were accounted for. KHB decomposition suggested that 30.16% of the association was mediated through underlying health conditions.

CONCLUSION: These findings suggest that familial or genetic factors associated with cancer susceptibility may also contribute to Long COVID risk. Further research is needed to explore potential biological mechanisms underlying this association.},
}

Humans
Female
*Neoplasms/epidemiology/genetics
Male
*COVID-19/epidemiology/virology
United States/epidemiology
Middle Aged
Adult
Risk Factors
Cross-Sectional Studies
Prevalence
Aged
SARS-CoV-2
Young Adult
Health Surveys

@article {pmid41527930,
year = {2026},
author = {Fernandes, TP and Santos, NA and Dahlgren, LN},
title = {Prospective study of long COVID-related psychological and biological outcomes in individuals with tobacco use disorder.},
journal = {Journal of addictive diseases},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/10550887.2025.2609140},
pmid = {41527930},
issn = {1545-0848},
abstract = {BACKGROUND: Individuals with tobacco use disorder (TUD) may be particularly vulnerable to the challenges following long COVID.

OBJECTIVE: This study assessed whether individuals with TUD and no prior neuropsychiatric conditions developed new symptoms following long COVID-19 infection.

METHODS: A cohort of 104 adults with TUD completed psychological and biological assessments before the COVID-19 pandemic and were reevaluated four months post-long COVID diagnosis. Evaluations covered mood symptoms, sleep, perceived stress, quality of life, and serum cortisol.

RESULTS: The participants exhibited marked increases in depressive symptoms, anxiety, insomnia, and perceived stress, accompanied by significant declines in sleep quality and quality of life (all p-values < 0.001). Serum cortisol levels decreased significantly, indicating altered HPA axis activity.

CONCLUSION: This study suggests that long COVID may disproportionately influence addictive disorders, not only by exacerbating existing vulnerabilities, but potentially contributing to the onset of new mental health challenges.},
}

@article {pmid41527239,
year = {2026},
author = {Goldschmidt, MI and Torensma, M and Beune, E and Agyemang, C and Rostila, M and Benfield, T and Norredam, M and Moseholm, E},
title = {Experiences of access to care, diagnosis and rehabilitation among a multiethnic patient population with long COVID in Denmark: A qualitative study.},
journal = {Scandinavian journal of public health},
volume = {},
number = {},
pages = {14034948251400105},
doi = {10.1177/14034948251400105},
pmid = {41527239},
issn = {1651-1905},
abstract = {AIMS: Several studies suggest that ethnic minorities are at higher risk of experiencing long COVID compared to majority populations. This study aimed to qualitatively explore the experiences of accessing care, diagnosis and rehabilitation among patients with long COVID in a multiethnic population in Denmark.

METHODS: We carried out 18 semi-structured interviews with individuals of Danish, Turkish and Moroccan background who were diagnosed with long COVID. Informants were sampled purposively to secure variation in sex, age, country of origin and immigration status. Our interview guide was developed using the theoretical framework of candidacy. Interviews were transcribed verbatim, member checked and subsequently analyzed using thematic framework analysis and NVivo software.

RESULTS: Our findings show that accessing care and rehabilitation for long COVID was difficult regardless of ethnic background. Following the novelty of COVID-19 and thus uncertainty of long COVID, informants had to self-advocate and navigate established and alternative healthcare services by themselves. Additionally, patients with Moroccan and Turkish minority background had to contend with experiences of differential treatment and of having their motives for seeking help questioned, while also finding it harder to benefit from the rehabilitation measures offered.

CONCLUSIONS: Our study demonstrates how the emergence of a new viral disease with unknown long-term sequelae resulted in a group of patients who largely carried the burden of getting better by themselves. Yet patients with an ethnic minority background experienced additional, worrying barriers. More research into relevant diagnosis, care and support for all long COVID patients is needed, especially among ethnic minorities.},
}

@article {pmid41527037,
year = {2026},
author = {Lange-Tal, T and Tuvia, N and Lazar, S and Farajh, Y and Bernstine, T and Abassi, Z and Edelstein, M and Jabal, KA},
title = {Is long-term disruption of the renin-angiotensin-aldosterone system associated with long COVID? A retrospective cohort study among healthcare workers.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-026-12527-z},
pmid = {41527037},
issn = {1471-2334},
}

@article {pmid41523874,
year = {2025},
author = {Jarrar, T and Halaseh, N and Doudin, D and Bael, P and Shaheen, A and Jobeh, E and Sada, AA and Awwad, AA and Alqtishat, B and Hallak, H},
title = {Long-Term Self-Reported Symptoms Among Adults After COVID-19 Infection in the West Bank: A Cross-Sectional Analysis.},
journal = {Global health, epidemiology and genomics},
volume = {2025},
number = {},
pages = {2867843},
pmid = {41523874},
issn = {2054-4200},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Male ; Adult ; Cross-Sectional Studies ; *Self Report ; Middle Aged ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Middle East/epidemiology ; Fatigue/epidemiology ; Prevalence ; },
abstract = {INTRODUCTION: With growing recognition of the prolonged effects of COVID-19, there is an urgent need to understand its extended clinical and public health implications across diverse settings. Long-term consequences following SARS-CoV-2 infection remain insufficiently studied in Middle Eastern populations. This study aimed to assess the prevalence of persistent COVID-19 symptoms among Palestinian adults and to evaluate their associations with hospitalization and recovery duration.

METHODS: This cross-sectional study was conducted on a randomized sample of 407 adult COVID-19 patients confirmed by the Palestinian Ministry of Health between November 25 and December 15, 2020. We used a standardized Arabic questionnaire to cover demographics, medical history, symptoms, complications, and physical activity. Data were gathered by phone interviews in October 2021. All data came from self-reports. With significance defined at p < 0.05, associations between the symptom duration, hospitalization, and recovery time were examined using descriptive statistics and chi-square tests.

RESULTS: The study population had a mean age of 40 years; 54% were female, and 70.3% had no previous medical history. Common complaints were fatigue (64.9%), anosmia (61.9%), joint pain (52.6%), and headache (51.8%). Hospitalization was necessary in 7.6% of patients, while 5.9% required oxygen or intubation. Most patients (92.6%) recovered in 4 months. The persistence of chest pain (χ [2], 16.225), shortness of breath (χ [2], 13.257), and lethargy (χ [2], 8.194) was significantly associated with hospitalization (p < 0.001). The persistence of the previously mentioned symptoms was significantly associated with the duration of recovery.

CONCLUSION: This study offers valuable insights into the long-term symptoms experienced by individuals recovering from COVID-19 in the West Bank. The findings carry implications for clinicians, public health authorities, and affected individuals, highlighting the importance of integrated care strategies and sustained support throughout the postacute phase of the disease.},
}

Humans
*COVID-19/epidemiology/complications
Female
Male
Adult
Cross-Sectional Studies
*Self Report
Middle Aged
SARS-CoV-2
Hospitalization/statistics & numerical data
Middle East/epidemiology
Fatigue/epidemiology
Prevalence

@article {pmid41523768,
year = {2025},
author = {Silvestri, C and Stasi, C and Profili, F and Bartolacci, S and Sessa, E and Tacconi, D and Villari, L and Carrozzi, L and Dotta, F and Bargagli, E and Donnini, S and Masotti, L and Rasero, L and Lavorini, F and Pistelli, F and Chimera, D and Sorano, A and D'alessandro, M and Pacifici, M and Milli, C and Voller, F},
title = {Evaluation of short and long-term laboratory and instrumental findings in COVID-19 patients hospitalized in Tuscany.},
journal = {World journal of experimental medicine},
volume = {15},
number = {3},
pages = {107220},
pmid = {41523768},
issn = {2220-315X},
abstract = {BACKGROUND: The World Health Organization defined long coronavirus disease 2019 (COVID-19) as the continuation or development of new symptoms 3 months after the initial severe acute respiratory syndrome coronavirus 2 infection, with these symptoms lasting for at least 2 months with no other explanation.

AIM: To evaluate the potential laboratory and instrumental findings (short-term and long-term) resulting from COVID-19.

METHODS: This longitudinal observational COVID-19 cohort study (March 1, 2020-March 1, 2021) was carried out on patients ≥ 18 years old who were admitted to the University Hospitals of Pisa, Siena and Careggi and the Azienda USL Toscana Nord Ovest, Sud Est and USL Centro Toscana and were subjected to follow-up. Follow-up was conducted between 0 day and 89 days, 90 days and 179 days, 180 days and 269 days, 270 days and 359 days, and more than 360 days after hospitalization.

RESULTS: Of 2887 patients (58.5% males, average age 66.2 years) hospitalized in the study period (March 1, 2020-March 1, 2021) carrying out at least one follow-up examination within 12 months of discharge, a total of 1739 patients (705 males, average age 66 years) underwent laboratory tests, of whom 714 patients (470 males, average age 63 years) underwent spirometry. Some laboratory test results remained above the threshold even at follow-up beyond 360 days (C-reactive protein: 36%, fibrin degradation fragment: 48.8%, gamma-glutamyl transferase: 16.8%), while others showed a return to normal range more quickly in almost all patients. Alterations in liver enzymes, hematocrit, hemoglobin, lymphocytes and neutrophils were associated with the risk of requiring oxygen therapy or forced expiratory volume in one second/forced vital capacity alterations at follow-up.

CONCLUSION: Alterations in liver enzymes, hematocrit or hemoglobin, lymphocytes and neutrophils were associated with risk outcomes (need for oxygen therapy or spirometry alterations). These imbalanced conditions may contribute to pulmonary dysfunction.},
}

@article {pmid41523623,
year = {2025},
author = {Kim, GJ and Alam, MA and Crabtree, JS and Rose, R and Lamers, SL and Chu, S and Horswell, R and Fort, D and Miele, L},
title = {Long COVID incidence across SARS-CoV-2 lineages and identification of conserved spike targets for multivalent vaccines.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e288},
pmid = {41523623},
issn = {2059-8661},
abstract = {BACKGROUND: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets.

METHOD: To estimate Long COVID incidence across variants, we linked 4789 SARS-CoV-2 sequences to 3090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) based definitions of Long COVID presentation developed by the N3C consortium.

RESULTS: 1,554 patients (1,536 Long COVID-negative) met Long COVID definitions, with 56.3% being female, 36.1% self-reported as African American, 5.5% self-reported as Hispanic/Latino, and 54.5% had received at least one vaccine dose 14 days prior to SARS-CoV-2 collection. Long COVID-positive patients were older (mean age 43.1 years) than negative patients (35.9 years; p = 0.0054) and were more likely to be female (p = 0.0001). Among unvaccinated patients, those with Long COVID were significantly younger than their vaccinated counterparts (p < 0.00001). Long COVID incidence varied by PANGO lineage, ranging between 14% in AY.13 to 67.8% in B.1.1.7. Analysis of spike protein diversity revealed eight conserved amino acid regions (Shannon entropy < 0.43), representing potential targets for vaccine design.

CONCLUSION: Long COVID rates across thousands of annotated SARS-CoV-2 sequences revealed lineage-specific risk and conserved epitopes for future interventions.},
}

@article {pmid41523183,
year = {2026},
author = {Rudroff, T},
title = {Neurological diversity and generalizability: building on AMPA receptor imaging advances in long COVID.},
journal = {Brain communications},
volume = {8},
number = {1},
pages = {fcaf499},
pmid = {41523183},
issn = {2632-1297},
abstract = {This scientific commentary refers to 'Systemic increase of AMPA receptors associated with cognitive impairment of long COVID' by Fujimoto et al. (https://doi.org/10.1093/braincomms/fcaf337).},
}

@article {pmid41522693,
year = {2026},
author = {Shahbaz, S and Rahmati, A and Syed, H and Elahi, S},
title = {Soluble CD14 promotes Th17 expansion and differentiation through gamma-aminobutyric acid and expands infidel innate lymphoid cells.},
journal = {PNAS nexus},
volume = {5},
number = {1},
pages = {pgaf406},
pmid = {41522693},
issn = {2752-6542},
abstract = {Interleukin-17 (IL-17) plays a central role in the pathogenesis of various autoimmune diseases. Soluble CD14 (sCD14), a marker of innate immune activation, is elevated in several inflammatory conditions. However, its influence on IL-17 production and the differentiation of Th17 cells remains poorly understood. We found that sCD14 enhances Th17-associated cytokine production and up-regulates critical transcription factors such as STAT3 and RORC. Notably, sCD14's effect on Th17 polarization was mediated indirectly through autologous sCD14-treated peripheral blood mononuclear cell (PBMC) supernatant (sCD14-PBMC-Sup). Additionally, we identified a distinct cytokine profile enriched for pro-inflammatory cytokines and chemokines in sCD14-treated T cells, further reinforcing the Th17-promoting role of sCD14. Interestingly, gamma-aminobutyric acid (GABA), a metabolite elevated in sCD14-treated monocytes, was identified as a potential contributor to Th17 polarization. GABA supplementation in T-cell cultures enhanced IL-17A secretion, indicating its role as a signaling molecule in T-cell differentiation. Our findings also revealed the expansion of innate lymphoid cell (ILC)2/3-like cells in T-cell cultures exposed to sCD14-PBMC-Sup and GABA, highlighting the potential role of monocytes in Th17-mediated immunity. Furthermore, while sCD14 promoted Th17 polarization, it simultaneously impaired T-cell activation and proliferation, suggesting an immunosuppressive effect mediated by soluble factors released from monocytes. These results underscore the dual role of sCD14 in modulating T-cell responses, promoting Th17 differentiation while suppressing T-cell effector functions. This study identifies a previously unrecognized role for sCD14 in promoting Th17 induction, highlighting its contribution to immune regulation and its potential as a therapeutic target in Th17-driven autoimmune conditions. Classification: Immunology.},
}

@article {pmid41521322,
year = {2026},
author = {Lank, GK and Budhiraja, S and Gaelen, JI and Mukherjee, S and Singer, T and Venkatesh, A and Jimenez, M and Miller, J and Lopez, M and Duax, CJ and Blahnik, D and King, D and Hanson, BA and Bawa, AP and Bharadwaj, S and Batra, A and Liotta, EM and Koralnik, IJ},
title = {Characterizing Neuro-PASC outcome with the mobile Neuro-COVID recovery care companion application.},
journal = {BMC neurology},
volume = {26},
number = {1},
pages = {24},
pmid = {41521322},
issn = {1471-2377},
mesh = {Humans ; *COVID-19/complications ; Female ; Male ; Middle Aged ; *Mobile Applications ; Aged ; Adult ; Quality of Life ; Patient Reported Outcome Measures ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Surveys and Questionnaires ; *Nervous System Diseases/etiology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects 14 million people in the US. Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating. However, the evolution of these symptoms and factors associated with recovery are poorly understood. This study aimed to characterize Neuro-PASC symptom evolution using a mobile phone application and assess user experience.

METHODS: The Neuro-COVID Recovery Care Companion (NCRCC) mobile application consists of questionnaires integrated within Northwestern Medicine's online MyChart platform which interfaces with the electronic medical record. Neuro-PASC patients completed daily surveys of twelve Neuro-PASC symptoms and their perceived percent recovery compared to their pre-COVID baseline. Patients also completed Patient-Reported Outcomes Measurement Information System (PROMIS) quality-of-life (QoL) surveys and NIH toolbox cognitive assessments at baseline and at 3-month follow up. Participants were retrospectively classified as "Improvers" or "Non-Improvers" based on the slope and range of their percent subjective recovery.

RESULTS: Data from 63 participants presenting an average of 12.7 months after symptom onset were analyzed, including 27 (42.9%) Improvers and 36 (57.1%) Non-Improvers. Fewer women were Improvers (50% vs 75.7%; p = 0.04). Multiple correspondence analysis showed that patients presenting with a constellation of anosmia, dysgeusia, and a lack of insomnia (p = 0.023) were less likely Improvers. Improvers had more fluctuations in their subjective recovery than Non-Improvers with greater mean variance (7.01 vs 3.79; p = 0.0004) and positive recovery slope (5.84 vs 0; p < 0.0001). There were no differences in QoL and cognition at initial assessment, but Improvers showed a trend toward increased processing speed and decreased sleep disturbance after 3 months. Both groups found the NCRCC application easy-to-use, useful, and satisfactory.

CONCLUSIONS: Our findings reveal previously unrecognized fluctuations in subjective recovery of Neuro-PASC, and that women and patients presenting with anosmia and dysgeusia are less likely to improve one year from COVID-19 onset. We found broad alterations in QoL in both groups suggesting that strategies to reduce sleep disturbance and improve cognition may contribute to subjective improvement. Our results suggest similar mobile applications may benefit patients with other ill-defined chronic diseases, by equipping and empowering them on their often windy road to recovery.},
}

Humans
*COVID-19/complications
Female
Male
Middle Aged
*Mobile Applications
Aged
Adult
Quality of Life
Patient Reported Outcome Measures
Post-Acute COVID-19 Syndrome
Retrospective Studies
Surveys and Questionnaires
*Nervous System Diseases/etiology
SARS-CoV-2

@article {pmid41520775,
year = {2026},
author = {Seo, G and Joo, H and Song, K and Kim, M and Jung, EJ and Kim, ES and Ko, JH and Lee, JS and Song, JY and Seo, JW and Choi, JY and Kwon, KT and Lee, SS and Park, WB and Choi, WS and Baek, YJ and Kim, YK and Jeong, HW and Jung, J and Lee, J},
title = {Static and Dynamic Scoring Systems for Post-acute Sequelae of SARS-CoV-2 in a Korean Cohort.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108378},
doi = {10.1016/j.ijid.2026.108378},
pmid = {41520775},
issn = {1878-3511},
abstract = {OBJECTIVES: Persistent symptoms after SARS-CoV-2 infection (PASC, long COVID) remain a major public-health concern. We developed a data-driven definition and static and dynamic PASC scoring systems in a multicenter, prospective-retrospective observational cohort across 12 South Korean institutions.

METHODS: Adults enrolled December 2022-March 2025 were followed up to 24 months; 8,761 were recruited (7,208 infected; 1,553 controls) and 4,668 met analysis criteria (4,388 infected; 280 controls). Using participant-reported symptoms, surveys, and laboratory data, we identified nine symptoms robustly associated with PASC, with anosmia/ageusia and fatigue most influential.

RESULTS: A static score integrating indicators observed within 24 months yielded an optimal threshold of 13, classifying 19% of infected participants and 4% of controls as PASC positive. A dynamic score tracking six-month intervals showed symptom burdens peaking at 0-5 months post-infection and declining thereafter; at the same threshold, 33% of infected participants were classified as PASC positive, reflecting temporal fluctuation.

CONCLUSIONS: These data establish a quantitative definition of PASC and introduce a dynamic scoring framework to identify and monitor PASC, supporting future clinical research and practice.},
}

@article {pmid41520672,
year = {2026},
author = {Carazo, S and Skowronski, DM and Ouakki, M and De Serres, G},
title = {Methodological considerations in the attribution of long COVID to first or second infection.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00775-3},
pmid = {41520672},
issn = {1474-4457},
}

@article {pmid41520671,
year = {2026},
author = {Zhang, B and Wu, Q and Jhaveri, R and Forrest, CB and Chen, Y},
title = {Methodological considerations in the attribution of long COVID to first or second infection - Authors' reply.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00776-5},
pmid = {41520671},
issn = {1474-4457},
}

@article {pmid41518079,
year = {2026},
author = {Lorenz, P and Steinbeck, F and Fricke, F and Mai, F and Bergmann-Ewert, W and Wossidlo, C and Reisinger, EC and Müller-Hilke, B},
title = {Patients Suffering From Post-COVID-19 Syndrome Feature Enhanced Antibody Reactivity Towards Specific Linear Epitopes Within EBV EBNA1.},
journal = {Scandinavian journal of immunology},
volume = {103},
number = {1},
pages = {e70088},
pmid = {41518079},
issn = {1365-3083},
support = {Sondervermögen MV Schutzfonds//Ministry of Science, Culture, Federal and European Affairs/ ; Säule Gesundhei GW-20-0004//Ministry of Science, Culture, Federal and European Affairs/ ; COVICare-M-V: ZMII2-2524FSB031//German Bundestag by the German government/ ; },
mesh = {Humans ; *Epstein-Barr Virus Nuclear Antigens/immunology ; *COVID-19/immunology/complications ; Male ; Female ; *Antibodies, Viral/immunology/blood ; *SARS-CoV-2/immunology ; Adult ; *Herpesvirus 4, Human/immunology ; Autoantibodies/immunology/blood ; Retrospective Studies ; Immunoglobulin G/immunology/blood ; Middle Aged ; Cross-Sectional Studies ; *Epitopes/immunology ; Epstein-Barr Virus Infections/immunology ; Immunity, Humoral ; Aged ; },
abstract = {Post-COVID-19 syndrome (PCS; also known as post-acute sequelae of COVID-19, PASC and Long COVID) manifests with various clinical symptoms of unclear aetiology that persist or develop months after acute infection with SARS-CoV-2. Potential triggers for PCS include reactivation of latent viruses and autoimmune reactions. In our retrospective cross-sectional and explorative study we compared 48 PCS patients with 48 individuals that recovered fully from COVID-19 (convalescents, CC). We focused on characterising humoral immunity by recording IgG antibody reactivity patterns against Epstein-Barr virus (EBV) EBNA1 antigen using peptide microarray and ELISA methodology as well as determining the presence of autoantibodies. The overall binding landscape of IgG antibodies for the EBV EBNA1 protein was similar for the patients with sequelae versus the convalescents. However, the PCS patients displayed stronger reactivity for epitopes contained within the glycine-alanine repeat region of EBNA1, in particular residues 90-325, and within the central part, amino acids 393-420. Intriguingly, in the latter case, the EBNA1 peptide (residues 405-419) that discriminated the PCS and CC cohorts was localised in a different segment C-terminal from the sequence proposed to be mechanistically associated with multiple sclerosis. The screening for autoantibodies against nuclear/cytoplasmic antigens in HEp-2 cells and against CRYAB, cardiolipin, beta-2-glycoprotein I, IFN-alpha2, IFN-omega, and IL-15 antigens did neither reveal higher prevalence nor increased reactivity in the PCS patients compared to the convalescents. In conclusion, elevated antibody levels against linear peptides derived from residues 90-325 and 405-419 of EBV EBNA1 were the most distinctive characteristics in our cohort of post-COVID-19 syndrome patients.},
}

Humans
*Epstein-Barr Virus Nuclear Antigens/immunology
*COVID-19/immunology/complications
Male
Female
*Antibodies, Viral/immunology/blood
*SARS-CoV-2/immunology
Adult
*Herpesvirus 4, Human/immunology
Autoantibodies/immunology/blood
Retrospective Studies
Immunoglobulin G/immunology/blood
Middle Aged
Cross-Sectional Studies
*Epitopes/immunology
Epstein-Barr Virus Infections/immunology
Immunity, Humoral
Aged

@article {pmid41517604,
year = {2026},
author = {Domanyi, R and Maitz, E and Andrianakis, A},
title = {Association Between Obesity and Post-COVID-19 Condition in Military Conscripts.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/jcm15010355},
pmid = {41517604},
issn = {2077-0383},
abstract = {Objectives: Obesity has been suggested as a possible risk factor for the post-COVID-19 condition, but most studies rely only on body mass index (BMI), which does not reflect body fat distribution. Waist-to-height ratio (WHtR) is a simple anthropometric indicator of central obesity and a practical proxy for body fat distribution, yet it has not been studied in relation to the post-COVID-19 condition. This study aimed to examine whether obesity, measured by BMI and WHtR, is associated with the post-COVID-19 condition. Methods: A total of 500 male military conscripts (aged 18 years) underwent anthropometric measurements (height, weight, and waist circumference). Participants with prior COVID-19 were asked whether they had persistent or new symptoms after infection. BMI categories followed WHO definitions, and WHtR ≥ 0.50 was used to define central obesity. Results: Of the 376 participants who had previously experienced COVID-19, 82 (21%) experienced the post-COVID-19 condition. Obesity (BMI ≥ 30) was more common among those with the post-COVID-19 condition than those without (15% vs. 5%). BMI-defined obesity was associated with higher odds of the post-COVID-19 condition (OR 2.80, 95%CI 1.25-6.24). Central obesity was also more frequent in the post-COVID-19 condition (26% vs. 14%) and was linked to increased odds as well (OR 2.18, 95% CI 1.20-3.97). Conclusions: Both BMI-defined obesity and central obesity were associated with the post-COVID-19 condition. While WHtR does not directly quantify body fat distribution, it represents a simple and feasible anthropometric indicator. Therefore, it may be an additional useful tool for identifying individuals at higher risk of prolonged symptoms after COVID-19 infection.},
}

@article {pmid41517410,
year = {2025},
author = {Brogna, B and Nunziata, M and Urciuoli, L and Romano, A and Laporta, A and Brogna, C},
title = {Spontaneous Pneumomediastinum in COVID-19 and Myasthenic-like Symptom Complications in Two Relatives: A Coincidence or Spike Toxicity with Thymic Response in Predisposed Individuals? Two Clinical Cases with a Comprehensive Literature Review.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/jcm15010159},
pmid = {41517410},
issn = {2077-0383},
abstract = {Pneumomediastinum (PM) in SARS-CoV-2 infections can have a multifaceted presentation. The most frequently described cases of spontaneous PM (SPM) occurred during the first waves of the SARS-CoV-2 pandemic due to alveolar fragility related to severe cases of interstitial pneumonia and vascular injury that predisposed to alveolar destruction and to the Macklin effect in PM development. Cases of SPM were also reported secondary to non-invasive mechanical ventilation (NIV) and to the increasing use of higher doses of corticosteroid therapy. However, true SPM in COVID-19 patients without any identifiable risk factors and presenting as a "Hamman syndrome" (HS) has also been observed, although it represents a very rare clinical entity. Both lung dysbiosis and spike protein toxicity could be implicated in SPM, including cases occurring after COVID-19 vaccination. Furthermore, a variety of clinical entities have been reported that are similar both in COVID-19 infection and after the related COVID-19 vaccination. We present two clinical cases (a 14-year-old boy and his mother), one presenting with SPM and both showing thymic hyperplasia, myasthenic-like symptoms, and long COVID features as a post-vaccination syndrome (PACVS). This report highlights how genetic and familial predisposition could play a role in the thymic response both in COVID-19 infection and after vaccination, involving the toxicity of the spike protein as a common denominator.},
}

@article {pmid41516301,
year = {2025},
author = {Stojanovic, M and Djuric, M and Nenadic, I and Bojic, S and Andrijevic, A and Popovic, A and Pesic, S},
title = {Vascular Complications of Long COVID-From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010433},
pmid = {41516301},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/pathology ; *Thrombosis/etiology/pathology ; *Endothelium, Vascular/physiopathology/pathology ; SARS-CoV-2 ; },
abstract = {Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated not only with respiratory illness but also with profound vascular and coagulation disturbances. Long COVID (LC) is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and palpitations. Mechanistically, SARS-CoV-2 induces direct endothelial injury, promotes a pro-inflammatory cytokine milieu, and activates platelets, leading to immunothrombosis and impaired fibrinolysis. Consequently, patients exhibit microthrombosis, elevated plasma D-dimer, fibrinogen dysregulation, and persistent hypercoagulability. Clinically, this translates into an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, as well as arterial thrombotic events such as myocardial infarction and stroke, which may persist months after acute infection. Understanding the interplay between endothelial injury, inflammation, and coagulation is crucial for risk stratification and the development of preventive and therapeutic strategies. We conducted a systematic narrative review of the literature, including human clinical and mechanistic studies identified through PubMed, Scopus and Web of Science up to 30 September 2025. This review synthesizes current evidence on vascular complications in LC, highlighting endothelial dysfunction as a central pathophysiological nexus linking the acute phase of SARS-CoV-2 infection with chronic LC manifestations.},
}

Humans
*COVID-19/complications/pathology
*Thrombosis/etiology/pathology
*Endothelium, Vascular/physiopathology/pathology
SARS-CoV-2

@article {pmid41516190,
year = {2025},
author = {Mcmillan, P and Turner, AJ and Uhal, BD},
title = {The Central Role of Macrophages in Long COVID Pathophysiology.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010313},
pmid = {41516190},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/physiopathology/pathology/virology ; *Macrophages/immunology/metabolism ; SARS-CoV-2/immunology ; Macrophage Activation/immunology ; Immunity, Innate ; Epigenesis, Genetic ; Spike Glycoprotein, Coronavirus/metabolism/immunology ; Animals ; },
abstract = {This review article attempts to provide a unifying hypothesis to explain the myriad of symptoms and predispositions underlying the development of PASC (Postacute Sequelae of COVID), often referred to as Long COVID. The hypothesis described here proposes that Long COVID is best understood as a disorder of persistent immune dysregulation, with chronic macrophage activation representing the fundamental underlying pathophysiology. Unlike transient post-viral syndromes, Long COVID involves a sustained innate immune response, particularly within monocyte-derived macrophages, driven by persistent spike protein (peripherally in MAIT cells and centrally in Microglial cells), epigenetic imprinting, and gut-related viral reservoirs. These macrophages are not merely activated temporarily but also become epigenetically "trained" into a prolonged inflammatory state, as demonstrated by enduring histone acetylation markers such as H3K27acDNA Reprogramming. It is proposed that recognizing macrophage activation as the central axis of Long COVID pathology offers a framework for personalized risk assessment, targeted intervention, and therapeutic recalibration.},
}

Humans
*COVID-19/immunology/physiopathology/pathology/virology
*Macrophages/immunology/metabolism
SARS-CoV-2/immunology
Macrophage Activation/immunology
Immunity, Innate
Epigenesis, Genetic
Spike Glycoprotein, Coronavirus/metabolism/immunology
Animals