@article {pmid41503716,
year = {2026},
author = {Gamillscheg-Müllner, P and Łaszewska, A and Diexer, S and Hoffmann, K and Simon, J and Mayer, S},
title = {Theoretically Universal, Practically Unequal: Socio-Economic Inequalities in Healthcare Access for Long Covid-19 Patients in Austria.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {1},
pages = {e70553},
doi = {10.1111/hex.70553},
pmid = {41503716},
issn = {1369-7625},
support = {SO68900010//Medical University of Vienna and the University of Vienna/ ; },
mesh = {Humans ; *COVID-19/therapy/epidemiology ; Female ; Male ; Austria/epidemiology ; Cross-Sectional Studies ; *Health Services Accessibility/statistics & numerical data ; Middle Aged ; Adult ; Retrospective Studies ; Socioeconomic Factors ; *Healthcare Disparities/statistics & numerical data ; Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Long Covid-19 (LC) patients have substantial treatment and care needs, yet research has shown that the majority of them experience healthcare access barriers. While qualitative studies indicate socio-economic and demographic access inequalities among LC patients, quantitative evidence remains limited. This study aims to assess socio-economic inequalities in healthcare access among LC patients in Austria, focusing on self-perceived barriers, facilitators and unmet healthcare needs.

METHODS: Retrospective cross-sectional data were collected from adult LC patients through online and paper-based surveys (10-12/2024), following a prior qualitative study. The survey assessed 47 barriers and 10 facilitators based on Levesque's 'access to care' framework, along with unmet healthcare needs overall and related to general practitioner (GP), specialist and hospital care. Overall barrier and facilitator scores were calculated. Inequalities related to gender, age, urbanicity, health-related background through training/employment, complementary private health insurance, and economic situation were examined in linear, logistic and ordered logistic regressions, controlling for clinical and demographic variables.

RESULTS: Overall, 433 LC patients completed the survey. Participants living in urban areas, with complementary private health insurance, or in a good economic situation reported fewer barriers, reflected in statistically significantly lower overall barrier scores. Income-related inequalities emerged particularly in relation to barriers in GP care, including not being taken seriously, attribution of symptoms to mental health conditions, burdensome costs, short consultation times, and limited availability of telemedicine or home visits. Facilitator scores, in contrast, did not differ by socio-economic factors. Living in a rural area was associated with a higher probability of unmet healthcare needs related to GP and specialist care. A poor economic situation was associated with a higher probability of reporting unmet needs related to specialist and hospital care. No evidence of gender-based inequalities was found.

CONCLUSIONS: Our findings reveal enhanced inequalities in LC healthcare access in an otherwise universal healthcare system. Contrary to prior research, we find income-related inequalities in GP access. Future policy efforts in Austria should consider that central case management through GP care may not be the most optimal set-up, especially without improved information, training, support and specialist referral opportunities.

The design of the survey and the hypotheses on healthcare access barriers and facilitators were directly informed by qualitative interviews from previous work with long Covid-19 (LC) patients, who shared their lived experiences with diagnosis, treatment and navigating the healthcare system. Additionally, LC patients piloted the survey before its launch and provided feedback. Representatives of patient LC groups and individual patients contributed to participant recruitment by sharing study materials within their networks.},
}

Humans
*COVID-19/therapy/epidemiology
Female
Male
Austria/epidemiology
Cross-Sectional Studies
*Health Services Accessibility/statistics & numerical data
Middle Aged
Adult
Retrospective Studies
Socioeconomic Factors
*Healthcare Disparities/statistics & numerical data
Aged
Surveys and Questionnaires
SARS-CoV-2

@article {pmid41503710,
year = {2026},
author = {Ribeiro, A and Hadavi, S and Gall, N and Hadden, RDM and Serra, J},
title = {Reply to: "Bridging Electrophysiology and Digital Health: Microneurography Findings in Long COVID Herald a New Era of AI-Powered Peripheral Nerve Monitoring".},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78141},
pmid = {41503710},
issn = {1531-8249},
}

@article {pmid41502583,
year = {2026},
author = {Rourke, L and Damant, R},
title = {A short version of the post-COVID-19 condition stigma questionnaire.},
journal = {Public health in practice (Oxford, England)},
volume = {11},
number = {},
pages = {100696},
doi = {10.1016/j.puhip.2025.100696},
pmid = {41502583},
issn = {2666-5352},
abstract = {OBJECTIVES: The purpose of this study was to develop a short version of the 40-item Post-COVID-19 Condition Stigma Questionnaire (PCCSQ) while preserving its factor structure, reliability, and validity. The PCCSQ is a sound tool for assessing the discrimination experienced by people with a diagnosis of long covid, but a shorter version would be less demanding of respondents experiencing fatigue and brain fog and easier for clinicians and researchers to administer.

STUDY DESIGN: This was an observational study.

METHODS: From the original 40-items measuring the 6-factor construct long covid stigma, we assembled 12 items that represented the factors and discriminated among participants with high and low levels of stigma. We administered the shorter questionnaire to 99 long covid patients and assessed several of its measurement properties.

RESULTS: The 12-item instrument maintains the 6-factor structure of long covid stigma, has a mean discrimination index of 0.40 (sd = 0.08; range 0.22-0.48), an internal consistency of α = 0.89, a split-half reliability of 0.86, and it correlates predictably with theoretically-related variables.

CONCLUSIONS: The PCCSQ-12 is a feasible, reliable and valid means of assessing patients' experience of long covid stigma.},
}

@article {pmid41499397,
year = {2026},
author = {Verma, AK and Tan, L and Schuster, N and Moye, SL and Lin, LC and Lowery, S and Duraisami, E and Lloréns, JEA and Qiu, Q and Hefti, M and Meyerholz, DK and Coleman, MC and Yu, CR and Albers, MW and Perlman, S},
title = {Combination antiviral and anti-inflammatory therapy mitigates persistent neurological deficits in mice post SARS-CoV-2 infection.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {2},
pages = {e2530209123},
doi = {10.1073/pnas.2530209123},
pmid = {41499397},
issn = {1091-6490},
support = {R01 NS36592//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01 AI129269/AI/NIAID NIH HHS/United States ; P01 AI060699/AI/NIAID NIH HHS/United States ; RF1 AG078297//HHS | NIH | National Institute on Aging (NIA)/ ; },
mesh = {Animals ; Mice ; *Antiviral Agents/therapeutic use/pharmacology ; *COVID-19/complications/virology/pathology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Humans ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Male ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Mice, Inbred C57BL ; *Nervous System Diseases/drug therapy/etiology/virology ; Brain/pathology ; },
abstract = {Post-acute sequelae of COVID-19 (PASC) encompasses persistent neurological disease, including olfactory and cognitive dysfunction. The basis for this dysfunction is poorly understood. Here, we report neurological dysfunction for at least 120 d postinfection in mice infected with a virulent nonneurotropic mouse-adapted SARS-CoV-2. Long after recovery from nasal infection, we observed diminished tyrosine hydroxylase expression in olfactory bulb glomeruli and in substantia nigra. Similar changes were observed in brains of COVID-19 deceased patients. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased proinflammatory cytokines, and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, similar to human neurodegenerative diseases. Treatment with antivirals (nirmatrelvir and molnupiravir) at the time of infection minimally prevented neurological abnormalities, consistent with patient data. In contrast, antivirals plus corticosteroids resulted in nearly complete recovery of neurological function. Remarkably, initiation of combined therapy even three days after infection improved outcomes. Together these results demonstrate that neurological dysfunction in SARS-CoV-2 infected mice resembles human neurodegenerative disease and indicate that minimizing inflammation early after SARS-CoV-2 infection may be critical for decreasing neurological PASC. The requirement for decreasing inflammation soon after infection may also explain why antiviral therapy has had inconsistent effects in patients.},
}

Animals
Mice
*Antiviral Agents/therapeutic use/pharmacology
*COVID-19/complications/virology/pathology
SARS-CoV-2
*COVID-19 Drug Treatment
Humans
*Anti-Inflammatory Agents/therapeutic use/pharmacology
Male
Disease Models, Animal
Drug Therapy, Combination
Female
Mice, Inbred C57BL
*Nervous System Diseases/drug therapy/etiology/virology
Brain/pathology

@article {pmid41498966,
year = {2026},
author = {Cao, Y and Lizano, P and Garza, AP and Dunay, IR and Zhou, X and Reuken, PA and Stallmach, A and Walter, M and Li, M and Besteher, B},
title = {Choroid plexus alterations in long COVID and their associations with IL-6.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41498966},
issn = {1433-8491},
support = {FKZ: 01EE2103//the DZPG (German Center for Mental Health)/ ; none//Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan/ ; K23MH122701//National Institute of Health grants/ ; },
abstract = {SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently leading to demyelination, white matter (WM) damage in long COVID, and clinical worsening. The role of the ChP in long COVID and its relationships to WM integrity, IL-6, clinical symptoms, and ACEIs/ARBs medications remains unclear. Fifty-two long COVID individuals, 21 COVID-19 survivors, and 26 healthy controls (HCs) completed Montgomery-Asberg Depression Rating Scale (MADRS), Montreal Cognitive Assessment (MoCA) and interleukin (IL) -6 assessments. Manually segmented ChP volume and global free water corrected WM integrity was compared among groups, and consideration of ACE inhibition on the ChP was examined. Partial correlations explored relationships among ChP volume, IL-6, fractional anisotropy tissue (FAt), and symptoms. ChP changes were also assessed at baseline and after one year. Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups. Larger ChP volume was significantly correlated to higher IL-6 levels (r = 0.478, p = 0.005) in long COVID. No ChP volume differences were found over time in the long COVID group or HCs that transitioned to COVID-19 survivors. COVID-19 survivors had larger ChP volume at follow-up compared to baseline (p = 0.04). The smaller ChP in long COVID seems to involve persistent but low-grade blood-CSF barrier dysfunction and epithelial stress. IL-6 levels may affect ChP permeability and suggest ongoing neuroinflammation in the long COVID group.},
}

@article {pmid41497070,
year = {2026},
author = {Obeagu, EI},
title = {Immunomodulatory strategies for managing cytokine storms in chronic COVID: mechanisms, therapeutic targets, and clinical advances.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {1},
pages = {653-659},
pmid = {41497070},
issn = {2049-0801},
abstract = {Chronic COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, is increasingly linked to sustained immune dysregulation, particularly cytokine storms that drive chronic inflammation and multi-organ complications. Understanding the mechanisms underlying cytokine dysregulation in chronic COVID is essential for developing effective therapeutic strategies aimed at restoring immune balance and mitigating long-term morbidity. This review critically examines current immunomodulatory strategies for managing cytokine storms in chronic COVID, including corticosteroids, cytokine-specific biologics, Janus kinase inhibitors, and emerging cell-based therapies. Additionally, the role of biomarker-guided precision medicine in personalizing treatment to optimize efficacy and safety is discussed. Challenges such as patient heterogeneity, timing and duration of therapy, and potential adverse effects are also addressed. Future research directions emphasize the need for robust clinical trials, novel therapeutic development, and integrated multidisciplinary care to improve patient outcomes. By tailoring immunomodulatory approaches based on individual immune profiles, it is possible to enhance the management of cytokine-driven inflammation in chronic COVID and advance the field toward more effective, personalized treatments.},
}

@article {pmid41496808,
year = {2025},
author = {Woods, JA and Hutchinson, NT and Powers, SK and Gomez-Cabrera, MC and Radak, Z and Leeuwenburgh, C and Cacciatore, S and Marzetti, E and Zhang, T and Garza, R and Sidebottom, C and Anderson, E and Durstine, JL and Sun, J and Ji, LL},
title = {Physical activity during COVID-19 pandemic: A 5-year retrospect.},
journal = {Sports medicine and health science},
volume = {7},
number = {6},
pages = {405-418},
pmid = {41496808},
issn = {2666-3376},
abstract = {The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019 (COVID-19) pandemic on human health and the role of physical activity (PA) during the 5-year pandemic. We aim to cover the immune system, the cardiopulmonary system, the musculoskeletal system, and the central nervous system (brain function), particularly among older adults, college students, and individuals with post-acute sequelae of COVID-19 (Long-COVID). The COVID-19 pandemic has given us many lessons, learned from the death of six million lives and tremendous disturbance to human life. First, we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection. Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines. The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research. Available evidence suggests that mitochondrial dysfunction, reduced microcirculation and latent immune activation play a major role, eventually impairing cardiovascular tolerance and peripheral bioenergetics. Second, the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor. Conversely, physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems. If not intervened, this interaction can lead to Long-COVID, a dangerous futile circle to cause systemic failure. Finally, the COVID-19 pandemic has exerted differential impacts on different populations. Thus, the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific, flexible and tailored to fit different patient populations.},
}

@article {pmid41496063,
year = {2026},
author = {Tang, L and Jie, Z and Zheng, D and Hua, Q and Cai, S and Li, C and Cai, Y and Jin, L and Yang, R and Zhang, Z},
title = {Effect of Fuzheng series of formulas on the psychological state, dyspnea, and quality of life in convalescent COVID-19 patients: A retrospective observational study.},
journal = {Medicine},
volume = {105},
number = {1},
pages = {e46375},
pmid = {41496063},
issn = {1536-5964},
mesh = {Humans ; *Quality of Life ; Retrospective Studies ; Male ; Female ; *Dyspnea/drug therapy/etiology/psychology ; Middle Aged ; *COVID-19/psychology/complications ; *Drugs, Chinese Herbal/therapeutic use ; Adult ; *COVID-19 Drug Treatment ; Aged ; SARS-CoV-2 ; },
abstract = {Post-infectious symptoms of COVID-19-such as persistent dyspnea, psychological disturbances, and reduced quality of life-continue to pose significant health challenges for convalescent patients. Traditional Chinese Medicine (TCM) has been widely used as a complementary therapeutic approach to alleviate post-COVID sequelae. This retrospective study evaluated the clinical effects of 2 TCM prescriptions, Fuzheng Yifei Formula (FZYF) and Fuzheng Anshen Formula (FZAS), on the psychological state, dyspnea, and quality of life among patients recovering from COVID-19. Medical records of 114 COVID-19 convalescent patients treated at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine were retrospectively reviewed. Based on the treatment regimen, patients were categorized into 2 groups: FZYF (n = 77) and FZAS (n = 37). Clinical data were collected at baseline, 7 days, 14 days, and during follow-up. Changes in psychological status, dyspnea severity, and quality-of-life scores were analyzed using validated assessment tools, including the General Health Questionnaire (GHQ-12), the Modified Borg Scale, and the 36-Item Short Form Survey (SF-36) Health Survey. Both FZYF and FZAS were associated with significant improvements in psychological well-being, with mean GHQ-12 scores decreasing from 14.5 at baseline to 9 at follow-up (P < .05). Dyspnea symptoms improved across both groups, with an average reduction of 3.5 points on the Modified Borg Scale. The SF-36 results indicated notable enhancements in both physical and mental health domains, showing mean improvements of 22% and 23%, respectively. No statistically significant difference was found between the 2 formulas, although FZYF showed slightly superior benefits in respiratory symptom relief. The retrospective analysis suggests that the FZYF may help alleviate long-term respiratory and psychological symptoms among COVID-19 convalescents, thereby potentially improving their overall quality of life. The FZAS, while showing comparable trends of benefit, appeared to exert relatively greater influence on mental and emotional well-being. However, these findings should be interpreted with caution given the non-randomized design and limited sample size, and further validation through large-scale controlled studies is warranted.},
}

Humans
*Quality of Life
Retrospective Studies
Male
Female
*Dyspnea/drug therapy/etiology/psychology
Middle Aged
*COVID-19/psychology/complications
*Drugs, Chinese Herbal/therapeutic use
Adult
*COVID-19 Drug Treatment
Aged
SARS-CoV-2

@article {pmid41494637,
year = {2026},
author = {Wu, Q and Zhao, Y and Fang, X and Chen, T and Zhang, C and Liu, Z and Wang, C},
title = {Longitudinal Changes in Long COVID Symptoms by Sex and Age Among Geriatric Residents of Residential Care Facilities: A Multicenter Cohort Study in Hefei, China.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {106071},
doi = {10.1016/j.jamda.2025.106071},
pmid = {41494637},
issn = {1538-9375},
abstract = {OBJECTIVES: This study aimed to investigate the symptomatic evolution of long COVID and to identify factors influencing its progression in a predominantly older population.

DESIGN: This was a prospective cohort study with long-term follow-up, conducting 3 assessment waves between January 8, 2023, and August 15, 2024.

SETTING AND PARTICIPANTS: The study included 228 of an initial cluster sample of 266 residents from 5 long-term care facilities in Hefei, China, all with prior SARS-CoV-2 infection, who completed all follow-ups.

METHODS: Data were collected via study-specific demographic questionnaires and a long COVID symptom scale. Descriptive statistics, Cochran's Q tests, t tests, partial correlations controlling for age, and generalized estimating equations were used to analyze symptom distribution, comparisons, longitudinal relationships, and influencing factors.

RESULTS: At T1, low mood (81.1%) and sleep disturbances (81.1%) were the most common symptoms. At T2, fatigue (54.8%) and pain in other body parts (59.2%) became the main symptoms. Dizziness (44.7%) was the most frequent symptom at T3. Independent samples t tests revealed that women had consistently higher total symptom scores than men (P < .05). Compared with the younger group (<76 years), the older group (≥76 years) had higher scores at T2 across multiple symptoms and in the overall score. Partial correlation analysis showed the correlation was strongest between T1 and T2 (r = 0.224, P = .001). The generalized estimating equations model indicated that men had a lower risk of symptoms in most organ systems (OR = 0.257-0.912).

CONCLUSIONS AND IMPLICATIONS: Long COVID symptoms in predominantly older individuals showed progressive improvement. Women had more severe symptoms and advanced age slowed the recovery process. However, long-term recovery depended on the individual. This study advocates for implementing personalized, stage-specific care models over standardized protocols in residential care facilities, emphasizing the need for targeted monitoring of high-risk subgroups such as women and older residents.},
}

@article {pmid41496174,
year = {2023},
author = {Kearney, GD and Hylock, R and Park, YM and Jones, K and Wall, B and Howard, R and Iyer, P and Clay, M and Endres-Dighe, S and Stoner, MCD and Li, L and Cajka, J and Rhea, S},
title = {Regional Trends of COVID-19-Like Illness-Related Emergency Department Visits in North Carolina, March 1, 2020-November 30, 2020.},
journal = {North Carolina medical journal},
volume = {84},
number = {1},
pages = {54-60},
pmid = {41496174},
issn = {2379-4313},
abstract = {BACKGROUND: An evaluation of emergency department (ED) visits and the number of patients seeking care for COVID-19-like illness (CLI) during the initial phases of the SARS-CoV-2 (COVID-19) pandemic in North Carolina has not been exclusively described.

PURPOSE: To characterize CLI-related ED visits across North Carolina from March 1 to November 30, 2020.

METHODS: This was a retrospective, descriptive study. Data from the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT) and the US Census Bureau were used to calculate CLI-related ED visit rates for the North Carolina resident patient population, and to compare and describe regional trends (Eastern, Piedmont, and Western).

RESULTS: A total of 133,193 CLI-related ED visits were evaluated. Across the 3 regions, CLI-related ED visits followed similar trends with the highest peaks being reported in mid-July and late November 2020. The Piedmont region experienced the highest percent (56.3%), while people aged 25-49 years accounted for the largest age group (35.0 %) of CLI-related ED visits. More CLI-related ED visits occurred for White individuals (47.8%), but the Eastern region had a far higher percent (44.8%) of reported CLI-related ED visits for Black and American Indian individuals compared to the rest of the state.

LIMITATIONS: ICD-10-CM codes were not available during the early weeks of the pandemic, which limited the ability to evaluate CLI-related data during this time.

DISCUSSION: This evaluation summarizes regional trends of CLI-related ED visits across North Carolina during the first 9 months of the COVID-19 pandemic. These results provide useful information and insight for public health officials, health care administrators, and policymakers.},
}

@article {pmid41494551,
year = {2026},
author = {Rubin, LH and Azola, A and Yoo-Jeong, M and Dastgheyb, RM and Easter, R and Ehrenspeck, A and Coughlin, JM and Vannorsdall, TD and Veenhuis, R and Wilson, T},
title = {Cognitive sequala of loneliness in long COVID: Differential associations by loneliness subtypes.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121101},
doi = {10.1016/j.jad.2025.121101},
pmid = {41494551},
issn = {1573-2517},
abstract = {BACKGROUND/OBJECTIVE: Loneliness is a risk factor for cognitive decline in aging and other clinical populations, but its role in long COVID (LC) remains poorly understood. Individuals with LC may be particularly vulnerable to loneliness due to debilitating, persistent symptoms and reduced functioning. We examined associations between overall loneliness and cognition in LC versus recovered controls, and whether loneliness subtypes (social, emotional) differentially relate to cognitive function.

METHODS: Individuals meeting 2024 National Academy of Science, Engineering and Medicine criteria (NASEM) for LC and reporting at least one neuropsychiatric symptom (n = 120), along with recovered controls (n = 51), completed the 6-item De Jong Gierveld Loneliness Scale and a cognitive test battery. Correlation analyses, corrected for false discovery rate, identified bivariate loneliness-cognition associations. Significant correlations were followed by age-adjusted regressions using residualized loneliness scores, which excluded variance shared with depression and social isolation.

RESULTS: LC participants reported higher overall, emotional, and social loneliness than controls. In bivariate analyses, greater overall and emotional loneliness were associated with more subjective cognitive complaints and poorer verbal fluency in the full sample and LC group, and with cognitive complaints and poorer verbal memory in controls. In adjusted models, residual overall and emotional loneliness remained significantly associated with fluency in LC and the full sample, and with memory in controls. Associations with cognitive complaints did not persist. Social loneliness showed weaker and inconsistent associations.

CONCLUSION: Overall and emotional loneliness are independently linked to objective cognitive difficulties. Findings highlight emotional loneliness as a potential target for cognitive intervention in LC and recovered individuals.},
}

@article {pmid41494535,
year = {2026},
author = {Wang, M and Chen, Y and Guo, M and Xie, P and Zhao, X and Chen, S and Deng, Y and Hu, R and Wan, Q and Zhou, J and Zhang, Z and Lan, K and Chen, H and Liu, Y},
title = {Impaired VLCFA-peroxisome-mediated intestinal epithelial repair causes gastrointestinal sequelae of long COVID.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2025.12.003},
pmid = {41494535},
issn = {1878-1551},
abstract = {Long COVID has emerged as a significant public health challenge with no effective treatments currently available, yet the pathophysiological mechanisms underlying its persistent gastrointestinal (GI) symptoms remain poorly understood. Here, integrating clinical data with transgenic animal models, we discover a critical role for impaired intestinal epithelial repair in the local intestinal etiology of long COVID. Mechanistically, we show that intestinal SARS-CoV-2 reservoirs disrupt very-long-chain fatty acid (VLCFA) metabolism, suppressing activation of peroxisome proliferator-activated receptor (PPAR) signaling and reducing peroxisome abundance. This disruption impairs intestinal stem cell differentiation and epithelial regeneration, resulting in prolonged GI symptoms including diarrhea, inflammation, and microbiota dysbiosis. Importantly, the FDA-approved sodium phenylbutyrate (NaPB) and fenofibrate alleviate these symptoms by promoting peroxisome proliferation and restoring epithelial repair. These findings provide insights into the GI pathogenesis of long COVID and highlight the therapeutic potential of enhancing the VLCFA-PPAR-peroxisome axis to mitigate persistent GI complications.},
}

@article {pmid41494490,
year = {2026},
author = {Messina, A and Bella, F and Maccarone, G and Avincola, G and Signorelli, MS},
title = {Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review.},
journal = {Journal of psychiatric research},
volume = {194},
number = {},
pages = {164-173},
doi = {10.1016/j.jpsychires.2026.01.007},
pmid = {41494490},
issn = {1879-1379},
abstract = {SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus-crucial for memory, emotional regulation, and executive functioning-is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood-brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances-most notably fatigue, apathy, low mood, and executive dysfunction-that typify dysexecutive syndrome in long-COVID. This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination-particularly its capacity to modulate microglial activation and support hippocampal neurogenesis-are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches. Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.},
}

@article {pmid41494204,
year = {2026},
author = {Shahbazi Khamas, S and Noij, LCE and Blankestijn, JM and Lap, CRR and van Houten, MA and Biesbroek, G and Maitland van der Zee, AH and Abdel-Aziz, MI and Goudoever, JBV and Alsem, MW and Brackel, CLH and Oostrom, KJO and Hashimoto, S and Brinkman, P and Terheggen-Lagro, SWJ},
title = {Exhaled breath-based clusters in children with post-COVID condition.},
journal = {Journal of breath research},
volume = {},
number = {},
pages = {},
doi = {10.1088/1752-7163/ae33e1},
pmid = {41494204},
issn = {1752-7163},
abstract = {Pediatric post-COVID condition (PPCC) presents as a heterogeneous disease with a broad spectrum of symptoms. This study aimed to identify distinct phenotypes of PPCC through an unbiased cluster analysis of exhaled metabolites, with the goal of identifying biomarkers to stratify patients. Methods: Exhaled breath samples were collected from children with physician-diagnosed PPCC. An unsupervised clustering approach was applied to the exhaled breath metabolites, and the resulting clusters were compared with clinical variables. Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was applied to find most discriminative metabolites between clusters. Results: A total of 54 children were included and categorized into two clusters. Compared to Cluster 1 (n=38), Cluster 2 (n=16) consisted predominantly of older girls (69%) with a median age of 16 years and exhibited more severe PPCC-related outcomes, including higher PROMIS fatigue scores. Six volatile organic compounds (VOCs) were identified as biomarkers that effectively differentiated the two clusters. These VOCs, previously reported in the literature, highlight metabolic and inflammatory disruptions and demonstrated high discriminatory performance (area under the receiver operating characteristic curve=1) Conclusion: This study found two distinct phenotypes of PPCC, and identified six discriminating VOCs, underscoring the potential of VOCs as non-invasive biomarkers for disease stratification in PPCC. While it could be a building block towards a better understanding of the metabolic disruptions underlying PPCC, further research with larger patient cohorts is necessary to elucidate the mechanisms driving these differences. .},
}

@article {pmid41493630,
year = {2026},
author = {Goretzki, SC and Bergelt, M and Weis, L and Hojeii, R and Gauß, G and Götte, M and Beller, R and Benson, S and Schönecker, A and Marina, AD and Gangfuß, A and Stehling, F and Pentek, C and von Loewenich, A and Hühne, T and Held, C and Voigt, S and Felderhoff-Müser, U and Schündeln, MM and Bruns, N and Eckert, K and Dohna-Schwake, C and Brasseler, M},
title = {Individualized online exercise therapy aids recovery in pediatric long-COVID-findings from an exploratory randomized controlled trial.},
journal = {European journal of pediatrics},
volume = {185},
number = {1},
pages = {54},
pmid = {41493630},
issn = {1432-1076},
mesh = {Humans ; Child ; Adolescent ; Female ; Male ; *COVID-19/rehabilitation ; Quality of Life ; *Exercise Therapy/methods ; Prospective Studies ; Treatment Outcome ; SARS-CoV-2 ; Feasibility Studies ; Walk Test ; Telemedicine ; },
abstract = {UNLABELLED: The purpose of this study is to evaluate the feasibility, safety, and effectiveness of an individualized online exercise therapy (IOET) designed to improve physical capacity and quality of life in children and adolescents with long-COVID. In a prospective, randomized, single-center exploratory trial, 14 patients aged 9-17 years with long-COVID (median symptom duration: 21 months) received either 6 or 12 weeks of IOET. Sessions were held twice weekly via telemedicine and individually adapted to physical ability and symptoms. Primary outcomes were functional performance (6-minute walk test [6MWT], sit-to-stand test [STST], and handgrip strength test [HST]). Secondary outcomes included school attendance, quality of life (PedsQL), safety, and self-reported recovery. All participants showed clinically improvements. In the 12-week IOET group, 6MWT increased from 396.0 to 616.3 m (+ 220.3 m, 95% CI 98.2-342.4), STST from 25.4 to 32.6 repetitions (+ 7.2, 1.9-12.5), and HST from 16.6 to 27.1 kg (+ 10.5 kg, 4.8-16.1). The 6-week group improved comparably (6MWT: 429.0 m to 601.6 m, (+ 172.6 m, 64.7-280.6); STST: 21.6 to 31.7 (+ 10.1, 3.1-17.1); HST: 17.3 to 22.1 kg (+ 4.8 kg (0.7-8.9)). School attendance rose from 58 to 97%, and PedsQL reflected improved quality of life and reduced fatigue. No adverse events or post-exertional symptom exacerbations occurred. Improvements persisted at the 3-month follow-up.

CONCLUSIONS:  IOET is feasible, safe, and associated with improved physical function, reintegration in everyday life, and its quality in pediatric long-COVID. These findings highlight IOET as a promising rehabilitation strategy and justify larger multicenter trials to confirm effectiveness and define optimal duration.

WHAT IS KNOWN: • Children and adolescents with long-COVID often experience persistent fatigue, impaired physical capacity, and reduced quality of life, with limited evidence-based treatment options available. • Exercise therapy has shown beneficial effects in other chronic pediatric conditions such as cancer- or fatigue-related syndromes, improving strength, well-being, and social participation.

WHAT IS NEW: • This exploratory randomized controlled trial demonstrates that individualized online exercise therapy is feasible, safe, and associated with clinically relevant improvements in physical function, quality of life, and school attendance in pediatric long-COVID, without negative side effects. • The findings highlight the potential of telemedicine-based rehabilitation strategies as accessible and effective treatment approaches for children and adolescents with post-infectious conditions such as long-COVID.},
}

Humans
Child
Adolescent
Female
Male
*COVID-19/rehabilitation
Quality of Life
*Exercise Therapy/methods
Prospective Studies
Treatment Outcome
SARS-CoV-2
Feasibility Studies
Walk Test
Telemedicine

@article {pmid41491558,
year = {2025},
author = {Liu-Galvin, R and Orlando, FA and Mainous, AG},
title = {Economic Burden of Long COVID: Lost Labor Costs in US Adults.},
journal = {Journal of the American Board of Family Medicine : JABFM},
volume = {38},
number = {5},
pages = {940-943},
doi = {10.3122/jabfm.2025.250059R1},
pmid = {41491558},
issn = {1558-7118},
mesh = {Humans ; *COVID-19/economics/epidemiology ; United States/epidemiology ; Adult ; Female ; *Cost of Illness ; Male ; Middle Aged ; *Sick Leave/economics/statistics & numerical data ; SARS-CoV-2 ; *Absenteeism ; Young Adult ; },
abstract = {INTRODUCTION: Long COVID (LC) is associated with significantly more days of work missed due to illness. Given this impact on the workforce, we estimated the lost labor costs associated with these additional missed workdays among individuals with LC in the US in 2022.

METHODS: 104,889,622 (weighted) adult full-time workers in the 2022 Medical Expenditure Panel Survey were categorized as: never had COVID-19, had COVID-19 without LC, and had LC. The estimated cost of lost labor from days of work missed due to illness/injury in 2022 was calculated as: (hours worked per week ÷ 5) × (hourly wage) × (days of work missed). Differences in mean costs were assessed using one-way ANOVA. The population-level lost labor cost associated with LC was estimated as (mean lost labor cost for LC - mean lost labor cost for never had COVID-19) × (number of full-time workers ≥18 years in the US in 2022 × prevalence of LC in the study population).

RESULTS: The total estimated lost labor cost from days of work missed due to illness/injury for individuals with LC was $15,863,994,281 (SE, $1,748,160,632). The mean lost labor cost for individuals with LC was more than twice that of individuals who never had COVID-19 and significantly higher than those who had COVID-19 without LC. The population-level lost labor cost associated with LC was estimated to be $12,784,168,675.20 (SE, $1,946,074,821.60).

DISCUSSION: These findings highlight the substantial economic impact of LC, totaling more than $12 billion in lost labor costs in 2022, emphasizing the need for targeted prevention and treatment strategies.},
}

Humans
*COVID-19/economics/epidemiology
United States/epidemiology
Adult
Female
*Cost of Illness
Male
Middle Aged
*Sick Leave/economics/statistics & numerical data
SARS-CoV-2
*Absenteeism
Young Adult

@article {pmid41490577,
year = {2026},
author = {Wilson, M and Pedersen, SG and Langeland, N and Cox, RJ and Aukrust, P and Dahl, TB and Sandvig, A and Wilhelmsen, M},
title = {Tailored Individual Follow-Ups Versus a One-Day Group Course in Patients With Long COVID (Post- COVID-19 Condition): Protocol for a Randomized Controlled Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e74113},
doi = {10.2196/74113},
pmid = {41490577},
issn = {1929-0748},
mesh = {Humans ; *COVID-19/rehabilitation/complications ; Adult ; Middle Aged ; Quality of Life ; Aged ; Adolescent ; Young Adult ; Male ; Female ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; Mobile Applications ; Self-Management/methods ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: The high prevalence of patients with post-COVID-19 condition, also called long COVID, even among those with mild initial disease, may have a large impact on both the individual and society. Disability in everyday life, reduced health-related quality of life and work capacity, strain on the health care system, and substantial socioeconomic costs are associated with long COVID. More research to investigate the effectiveness of rehabilitation services is warranted.

OBJECTIVE: This study aims to examine the effectiveness of tailored individual follow-ups versus a 1-day group course in patients with long COVID. Additionally, the feasibility and use of a mobile app for self-monitoring goal achievement will be assessed.

METHODS: This is a single-center, parallel-group, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 62 outpatients aged 18-65 years with long COVID will be randomized to either a rehabilitation program with individual follow-up consultations or a 1-day self-management group course. The individual intervention incorporates setting goals, teaching cognitive behavioral strategies, energy management (pacing), and a supervised gradual increase in both physical and cognitive activities tailored to individual tolerance levels. The primary outcome is the between-group difference in health-related quality of life, measured using the EQ-5D-5L index at 6 months. Secondary outcomes include improvements in symptoms, work participation, neurocognitive function, and app usability, assessed at 3, 6, and 12 months, depending on the outcome measure.

RESULTS: Data enrollment started in October 2023. A total of 62 participants were included by November 2024. Data collection is planned to be completed in November 2025.

CONCLUSIONS: Long COVID poses substantial challenges for both individuals and society, underscoring the need for effective rehabilitation strategies. This study will provide valuable insights into the benefits of an individualized outpatient rehabilitation program. The results from this clinical trial will help guide future treatment recommendations and may improve long-term outcomes for affected patients. Additionally, the study will generate important knowledge about neuropsychological function and digital self-management tools in long COVID rehabilitation.},
}

Humans
*COVID-19/rehabilitation/complications
Adult
Middle Aged
Quality of Life
Aged
Adolescent
Young Adult
Male
Female
SARS-CoV-2
Randomized Controlled Trials as Topic
Mobile Applications
Self-Management/methods
Post-Acute COVID-19 Syndrome

@article {pmid41490011,
year = {2026},
author = {Rhee, KE and Thaweethai, T and Pant, DB and Stein, CR and Salisbury, AL and Kinser, PA and Kleinman, LC and Gallagher, R and Warburton, D and Mohandas, S and Snowden, JN and Stockwell, MS and Tantisira, KG and Flaherman, VJ and Teufel, RJ and Castro, L and Chung, A and Espinoza Esparza, J and Hockett, CW and Isidoro-Chino, M and Krishnan, A and McCormack, LA and Nabower, AM and Nahin, ER and Rosas, JM and Siddiqui, S and Szmuszkovicz, JR and Vangeepuram, N and Zimmerman, E and Brown, HE and Carmilani, M and Coombs, K and Fisher, L and Witvliet, MG and Wood, JC and Milner, JD and Rosenzweig, EB and Irby, K and Karlson, EW and Qian, Z and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, HS and Foulkes, AS and Gross, RS and , and Aschner, JL and Atz, AM and Banerjee, D and Bogie, A and Bukulmez, H and Clouser, K and Cottrell, LA and Cowan, K and D'Sa, VA and Dozor, AJ and Elliott, AJ and Faustino, EVS and Fiks, AG and Gaur, S and Gennaro, ML and Gordon, ST and Hasan, UN and Hester, CM and Hogan, AH and Hsia, DS and Kaelber, DC and Kosut, JS and Krishnan, S and McCulloh, RJ and Michelow, IC and Nolan, SM and Oliveira, CR and Pace, WD and Palumbo, P and Raissy, H and Reyes, A and Ross, JL and Salazar, JC and Selvarangan, R and Stevenson, MD and Werzberger, A and Westfall, JM and Zani, K and Zempsky, WT and Chan, J and Metz, TD and Newburger, JW and Truong, DT and Feldman, CH and Aupperle, R and Baker, FC and Banich, MT and Barch, DM and Baskin-Sommers, A and Bjork, JM and Dapretto, M and Brown, SA and Casey, BJ and Chang, L and Clark, DB and Dale, AM and Ernst, TM and Fair, DA and Feldstein Ewing, SW and Foxe, JJ and Freedman, EG and Friedman, NP and Garavan, H and Gee, DG and Gonzalez, R and Gray, KM and Heitzeg, MM and Herting, MM and Jacobus, J and Laird, AR and Larson, CL and Lisdahl, KM and Luciana, M and Luna, B and Madden, PAF and McGlade, EC and Müller-Oehring, EM and Nagel, BJ and Neale, MC and Paulus, MP and Potter, AS and Renshaw, PF and Sowell, ER and Squeglia, LM and Uddin, LQ and Wilson, S and Yurgelun-Todd, DA},
title = {Social Determinants of Health and Pediatric Long COVID in the US.},
journal = {JAMA pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamapediatrics.2025.5485},
pmid = {41490011},
issn = {2168-6211},
abstract = {IMPORTANCE: Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID.

OBJECTIVE: To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US.

This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n = 903) and adolescents (12-17 years; n = 3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024.

EXPOSURE: Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models.

MAIN OUTCOMES AND MEASURES: Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices.

RESULTS: The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results.

CONCLUSIONS AND RELEVANCE: In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.},
}

@article {pmid41488386,
year = {2026},
author = {Cash, N and Koebel, MC and Badran, BW and Schumann, AY and McTeague, LM and Uhde, TW and Schlosser, RJ and Cortese, BM},
title = {Study of Chemosensory Enhancement through Neuromodulation Training (SCENT): Design and methodology of a randomized clinical trial for COVID-related persistent smell dysfunction.},
journal = {Contemporary clinical trials communications},
volume = {49},
number = {},
pages = {101582},
pmid = {41488386},
issn = {2451-8654},
abstract = {BACKGROUND: Few evidence-based treatments exist for COVID-related persistent smell dysfunction. While smell/olfactory training (ST) has emerged as a widely prescribed, first line treatment, rigorous study is required to determine its efficacy in Long COVID. Additional study and development of adjunctive methods to improve the efficacy of ST is also needed.

METHODS: This paper details the study design and methodology for a large, at-home, randomized, controlled trial designed to determine whether ST and/or trigeminal nerve stimulation (TNS)-enhanced ST improves Long COVID-related disturbances in smell function, mood, sleep, and cognition. Adults with COVID-related persistent smell dysfunction (N = 180) will be recruited and randomized to self-administer ST, placebo smell training (PBO), or TNS-enhanced ST daily for 12 weeks. Our primary objectives are to i) determine the efficacy of ST, compared to any natural gain in function, on olfactory-specific deficits, ii) determine the TNS-enhanced effects of ST on olfactory-specific deficits, and iii) determine if TNS-enhanced ST, compared to ST, is also more efficacious in the treatment of other symptoms of Long COVID.

CONCLUSION: Post COVID persistent smell dysfunction and related deficits are relatively common with very few treatment options. Our proposed study will lay the groundwork for further development of ST and TNS as evidence-based treatments for Long COVID.},
}

@article {pmid41488148,
year = {2025},
author = {Shitaye, G and Getie, M and Mekonnen, Z and D'Abrosca, G and Fattorusso, R and Isernia, C and Amuamuta, A and Malgieri, G},
title = {Molecular analysis of long COVID and new-onset diabetes mellitus: pathobiological relationships and current mechanistic views.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1737894},
pmid = {41488148},
issn = {1664-2392},
mesh = {Humans ; *COVID-19/complications/metabolism/pathology/epidemiology ; *SARS-CoV-2 ; *Diabetes Mellitus, Type 2/epidemiology/etiology/virology/metabolism/pathology ; *Diabetes Mellitus, Type 1/epidemiology/metabolism/etiology/virology ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; Insulin Resistance ; },
abstract = {Long COVID, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), refers to a range of persistent health effects associated with SARS-CoV-2 infection. Long COVID is a complex, multisystem disorder that can affect nearly every organ system and is strongly linked with the incidence of diabetes and other chronic conditions. Increasing evidence also connects persistent SARS-CoV-2 infection with the development of new-onset diabetes and other metabolic disorders. In this review, we assess the current evidence and discuss the incidence of new-onset diabetes, along with the pathobiological mechanisms by which SARS-CoV-2 may contribute to the progression of both new-onset type 1 and type 2 diabetes mellitus (T1DM and T2DM). We summarize the latest understanding of the molecular and cellular mechanisms underlying SARS-CoV-2-associated new-onset diabetes. Potential mechanisms include direct damage to pancreatic β-cells, inflammation, insulin resistance, and autoimmune responses. Dysregulation of the ACE2/renin-angiotensin system (RAS) pathway has been linked to multiple inter-organ pathologies, and increased inflammatory cytokines together with dysregulation of interferon regulatory factors (IRFs)-such as overexpression of IRF1-appear to represent key mechanistic links to widespread tissue damage and metabolic alterations. Moreover, the presence of viral RNA or viral RNA fragments may directly damage pancreatic islets, contributing to insulin resistance and β-cell dysfunction that, in turn, may promote the development of new-onset diabetes. In light of these findings, this review further examines evidence supporting the persistence of SARS-CoV-2 RNA in PASC reservoir tissues, including the pancreas, and its potential association with the development of new-onset diabetes mellitus.},
}

Humans
*COVID-19/complications/metabolism/pathology/epidemiology
*SARS-CoV-2
*Diabetes Mellitus, Type 2/epidemiology/etiology/virology/metabolism/pathology
*Diabetes Mellitus, Type 1/epidemiology/metabolism/etiology/virology
Renin-Angiotensin System
Post-Acute COVID-19 Syndrome
Insulin Resistance

@article {pmid41487856,
year = {2025},
author = {Van Cleve, R and Lienau, A and Sanchez Garcia, J},
title = {Elevated Risk of an Emergency Department Admission Associated With Long COVID Diagnosis Within the US Veteran Population.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e98410},
pmid = {41487856},
issn = {2168-8184},
abstract = {Long COVID has emerged as a significant public health concern, potentially affecting millions of people over the next decade. By examining the risk of an emergency department (ED) visit associated with long COVID across a population, we can see the population-level severity of long COVID. This study aims to quantify the change in risk for ED visits in the six months following COVID-19 infection for people diagnosed with long COVID compared to those who are only infected with COVID-19 but not diagnosed with long COVID. The study compared the risk of an ED visit between veterans with long COVID and those with only COVID-19 infection. We examined the risk of an ED visit for these two groups in the six months before and the six months after being infected with COVID-19. Data came from the Veterans Health Administration (VHA) electronic medical records, specifically veterans who used the Veterans Affairs (VA) healthcare system and had an initial case of COVID-19 between March 1, 2021, and December 21, 2021. We examined ER visits six months before and after testing positive for COVID-19. The outcome of interest was the risk of an ED visit for people diagnosed with long COVID compared to people who only contracted COVID-19 and were not diagnosed with long COVID. In the six months after contracting long COVID, veterans eventually diagnosed with long COVID had a 34% higher risk of ED visits compared to those who contracted COVID-19 but never developed long COVID. Between three and six months post-infection, the risk of ED visits was 21% higher in the long COVID group. Long COVID can be a severe condition whose effects can last months after infection and diagnosis. Certain policies need to be implemented to manage the symptoms of this disease and reduce the need for emergency department services.},
}

@article {pmid41486438,
year = {2025},
author = {Seo, JW and Seo, YB and Kim, SE and Kim, Y and Kim, EJ and Kim, T and Kim, T and Lee, SH and Lee, E and Lee, J and Jeong, YH and Jung, YH and Choi, YJ and Song, JY},
title = {Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19.},
journal = {Infection & chemotherapy},
volume = {57},
number = {4},
pages = {478-521},
doi = {10.3947/ic.2025.0151},
pmid = {41486438},
issn = {2093-2340},
support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; },
abstract = {The guidelines presented herewith are based on the "Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19 (PASC)" published in Infection & Chemotherapy in March 2024; these guidelines have been refined by incorporating the most recent Korean and international research findings and clinical evidence published since then. In the context of patients experiencing various physical and mental symptoms that persist long after the acute phase of coronavirus disease 2019 (COVID-19) infection, the diagnosis and management of PASC has emerged as a novel public health challenge. These guidelines are intended to provide standardized diagnostic and management recommendations applicable to the Korean healthcare setting and were developed through a comprehensive review of existing guidelines from organizations such as the World Health Organization, the United States National Institutes of Health, the United Kingdom National Institute for Health and Care Excellence, and the European Society of Clinical Microbiology and Infectious Diseases, along with the latest meta-analyses and Korean cohort studies. PASC is defined as the persistent presence of symptoms and signs lasting more than 3 months after COVID-19 diagnosis for which the symptoms cannot be explained by alternative diagnoses. The revised guidelines emphasize the importance of integrated management for patients with PASC, including a multidisciplinary approach considering risk groups, symptom-specific assessment, and rehabilitation and psychological interventions, based on a total of 32 key questions. This revision reflects rapidly evolving research trends regarding the long-term effects of COVID-19 and is expected to serve as an evidence-based standard guideline for future patient care, clinical research, and health policy development in Korea.},
}

@article {pmid41485406,
year = {2026},
author = {Case, SJ and Sabik, L and Grant, H},
title = {Factors associated with long COVID among cancer survivors: A population-based analysis.},
journal = {Cancer epidemiology},
volume = {100},
number = {},
pages = {102984},
doi = {10.1016/j.canep.2025.102984},
pmid = {41485406},
issn = {1877-783X},
abstract = {INTRODUCTION: Cancer survivors endure unique immune system suppression as a result of their cancer treatment, potentially making them susceptible to long COVID in ways that differ from the general population. The purpose of this study is to assess what factors are associated with long COVID among cancer survivors.

METHODS: Observational, cross-sectional data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS) survey were analyzed. The main outcome of interest was the prevalence of long COVID among cancer survivors who had tested positive for COVID-19. Bivariate analyses were conducted comparing those who did and did not have long COVID, and logistic regression models were used to determine the sociodemographic variables and individual health factors associated with long COVID among cancer survivors.

RESULTS: In this sample, 15.2 % of cancer survivors who had tested positive for COVID-19 indicated they had long COVID. Cancer survivors who were male, older, received flu and COVID-19 vaccinations, and did not have diabetes or asthma had significantly lower odds of having long COVID.

CONCLUSION: This study provides insight into what sociodemographic and health-related factors are associated with the presence of long COVID, including age, sex, vaccination status, and comorbid conditions. Future longitudinal studies are warranted to establish causal patterns.},
}

@article {pmid41484677,
year = {2026},
author = {White, RA and Salamanca, BV and Angelsen, A and Zakiudin, DP and Andries, A and Nyborg, GA},
title = {Excess primary healthcare consultations in Norway in 2024 compared to pre-COVID-19-pandemic baseline trends.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13690-025-01817-8},
pmid = {41484677},
issn = {0778-7367},
abstract = {BACKGROUND: The risk of post-acute sequelae of COVID-19 (PASC) is estimated at 3-6% per infection in 2024. We hypothesized that widespread SARS-CoV-2 infections could lead to population-level consequences. Our previous study identified substantial increases in Norwegian primary healthcare consultations in 2023-compared to pre-pandemic levels-for conditions associated with acute COVID-19 and PASC. This study extended that analysis to 2024. We then assessed whether observed patterns were compatible with our hypothesis.

METHODS: We used data from the Norwegian Syndromic Surveillance System, which captures nationwide primary healthcare consultations for 102 ICPC-2 codes (out of a possible 710) that are relevant for infectious disease surveillance and some post-acute infection syndromes. Bayesian linear regression models were fitted to 2010-2019 trends, adjusting for population changes, to estimate expected values for 2024. Excess consultations were calculated by age and sex. A COVID-19 community spread was proxied by vaccination-adjusted weekly hospitalization rates.

RESULTS: In 2024, there were 17,800,365 consultations, corresponding to an absolute excess of 1,185,231 consultations, or a 7.1% relative excess, compared to the modelled baseline. The 10 code combinations with largest absolute excess in 2024 were respiratory infections (325,726 excess consultations; 20% relative excess), fatigue (205,381; 70%), psychological symptom/complaint other (188,978; 87%), acute stress reaction (182,079; 76%), feeling depressed (126,783; 133%), hyperkinetic disorder (112,763; 116%), abdominal pain/cramps general (84,544; 29%), memory disturbance (39,177; 63%), conjunctivitis (34,643; 59%), and infectious disease other/NOS (33,556; 81%). COVID-19 community spread showed the strongest correlations with conjunctivitis, strep throat, respiratory infections as a group (R**), fatigue, infectious disease other, memory disturbances, and pneumonia. Deviations from pre-pandemic trends varied: respiratory and psychological disorders worsened from 2020 onward and several conditions showed dramatic excess from 2022-2024. Females 15-29, children, adolescents, and young adults had disproportionately large relative excesses for consultations for memory disturbances.

CONCLUSIONS: Primary healthcare consultations in 2024 significantly exceeded pre-pandemic expectations, especially for conditions linked to acute COVID-19 and PASC, though the two cannot be differentiated in these data. While other factors undoubtedly also play a role, findings are compatible with ongoing population-level health impacts associated with repeated SARS-CoV-2 infections, particularly among women, children, adolescents, and young adults. These results emerged under a national COVID-19 strategy that does not account for post-acute consequences of SARS-CoV-2 infection.},
}

@article {pmid41484589,
year = {2026},
author = {Kamdem, OL and Dupre, C and Guyot, J and Ruiz, L and Nekaa, M and Botelho-Nevers, E and Bongue, B},
title = {Task delegation in emerging chronic diseases: Long COVID care as a paradigm - a cross-sectional study.},
journal = {BMC nursing},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12912-025-04249-5},
pmid = {41484589},
issn = {1472-6955},
support = {Grant number: ANRS283//ANRS - Agence Nationale de la Recherche / Emerging Infectious Diseases./ ; },
}

@article {pmid41484172,
year = {2026},
author = {Doni Jayavelu, N and Samaha, H and Wimalasena, ST and Hoch, A and Gygi, JP and Gabernet, G and Ozonoff, A and Liu, S and Milliren, CE and Levy, O and Baden, LR and Melamed, E and Ehrlich, LIR and McComsey, GA and Sekaly, RP and Cairns, CB and Haddad, EK and Schaenman, J and Shaw, AC and Hafler, DA and Montgomery, RR and Corry, DB and Kheradmand, F and Atkinson, MA and Brakenridge, SC and Agudelo Higuit, NI and Metcalf, JP and Hough, CL and Messer, WB and Pulendran, B and Nadeau, KC and Davis, MM and Gen, LN and Fernandez Sesma, A and Simon, V and Krammer, F and Kraft, M and Bime, C and Calfee, CS and Erle, DJ and Langelier, CR and , and Guan, L and Maecker, HT and Peters, B and Kleinstein, SH and Reed, EF and Augustine, AD and Diray-Arce, J and Becker, PM and Rouphael, N and Altman, MC},
title = {Machine learning models predict long COVID outcomes based on baseline clinical and immunologic factors.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {1},
pmid = {41484172},
issn = {2730-664X},
abstract = {BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID, remain a significant health issue that is incompletely understood. Predicting which acutely infected individuals will develop long COVID is challenging due to the absence of established biomarkers, clear disease mechanisms, or well-defined sub-phenotypes. Machine learning (ML) models may address this gap by leveraging clinical data to enhance diagnostic precision.

METHODS: Clinical data, including antibody titers and viral load measurements collected at the time of hospital admission, are used to predict the likelihood of acute COVID-19 progressing to long COVID. Machine learning models are trained and evaluated for predictive performance. Feature importance analysis is performed to identify the most influential predictors.

RESULTS: The machine learning models achieve median AUROC values ranging from 0.64 to 0.66 and AUPRC values between 0.51 and 0.54, demonstrating predictive capabilities. Low antibody titers and high viral loads at hospital admission emerge as the strongest predictors of long COVID outcomes. Comorbidities-such as chronic respiratory, cardiac, and neurologic diseases-and female sex are also identified as significant risk factors.

CONCLUSIONS: Machine learning models identify patients at risk for developing long COVID based on baseline clinical characteristics. These models guide early interventions, improve patient outcomes, and mitigate the long-term public health impacts of SARS-CoV-2.},
}

@article {pmid41483427,
year = {2026},
author = {Schwartz, CE and Borowiec, K},
title = {Toward characterizing brain fog in long COVID: correlates and impact on measurement metrics.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {1},
pages = {22},
pmid = {41483427},
issn = {1573-2649},
}

@article {pmid41482843,
year = {2026},
author = {Duru, EE and Okoye, G and Lee, S and Weir, P and Kim, J},
title = {Comparison of Healthcare Expenditures Among Individuals With and Without Long COVID in the United States.},
journal = {Inquiry : a journal of medical care organization, provision and financing},
volume = {63},
number = {},
pages = {469580251410890},
doi = {10.1177/00469580251410890},
pmid = {41482843},
issn = {1945-7243},
mesh = {Humans ; *Health Expenditures/statistics & numerical data ; United States/epidemiology ; *COVID-19/economics/epidemiology/therapy ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; SARS-CoV-2 ; Young Adult ; Hospitalization/economics/statistics & numerical data ; },
abstract = {Long COVID increases healthcare utilization, yet differences in healthcare spending patterns between individuals with and without long COVID remain poorly characterized, especially at the national level. To evaluate differences in healthcare expenditures among U.S. adults with and without long COVID using nationally representative data. This cross-sectional study analyzed data from the 2022 Medical Expenditure Panel Survey (MEPS), including 16 762 unweighted adults (weighted population: 239 915 159). Healthcare spending outcomes included total expenditures and specific categories including office-based care, outpatient services, emergency room visits, hospital admissions, home healthcare, and prescription medications. A survey-weighted generalized linear model (GLM) with a log link and gamma distribution was used to estimate adjusted differences in expenditures between groups. Individuals with long COVID had significantly higher total healthcare expenditures (mean $11 567; SD $25 334) compared to those without long COVID ($7448; SD $21 734, P < .01). After adjusting for demographic characteristics, insurance status, chronic conditions, and other potential confounders, individuals with long COVID incurred 40% higher total expenditures (β = 1.40, P = .01). Expenditures were significantly elevated for office-based visits (35% higher; β = 1.35, P = .02) and outpatient services (118% higher; β = 2.18, P < .01). No significant differences were found in emergency room, hospital admissions, or dental care expenditures. Long COVID imposes a substantial financial burden on individuals and healthcare systems, primarily through increased outpatient and office-based service utilization. Understanding these spending patterns can help inform policy decisions, optimize healthcare resource allocation, and guide targeted interventions to manage long COVID more effectively.},
}

Humans
*Health Expenditures/statistics & numerical data
United States/epidemiology
*COVID-19/economics/epidemiology/therapy
Cross-Sectional Studies
Female
Male
Middle Aged
Adult
Aged
Adolescent
SARS-CoV-2
Young Adult
Hospitalization/economics/statistics & numerical data

@article {pmid41482551,
year = {2026},
author = {},
title = {A role for chronic inflammation in long COVID.},
journal = {Nature immunology},
volume = {27},
number = {1},
pages = {12-13},
pmid = {41482551},
issn = {1529-2916},
}

@article {pmid41481665,
year = {2026},
author = {Martoreli Júnior, JF and O Pedroso, A and Lima, LDES and P Gusmão, CM and G Menegueti, M and F C Coêlho, H and Zamarioli, CM and Silva, ACOE and R O Naiff, G and Gir, E and K Reis, R},
title = {Prevalence and associated factors with long COVID in the Brazilian population: The role of health-related behaviors and sociodemographic characteristics.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0339612},
doi = {10.1371/journal.pone.0339612},
pmid = {41481665},
issn = {1932-6203},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; Prevalence ; Adult ; Cross-Sectional Studies ; Aged ; SARS-CoV-2/isolation & purification ; Risk Factors ; *Health Behavior ; Young Adult ; Adolescent ; Sociodemographic Factors ; },
abstract = {The disease caused by the 2019 coronavirus (COVID-19) has resulted in unprecedented morbidity and mortality worldwide, with many individuals experiencing persistent symptoms and a decline in quality of life after infection. This study aims to analyze the prevalence and associated factors of long COVID in the Brazilian population, focusing on disease severity and immunization status. This observational, cross-sectional web survey employed a quantitative approach to analyze data from 4,231 participants, focusing on the prevalence and associated factors of long COVID. Data were analyzed using inferential statistical methods to identify factors associated with the outcome. A multivariable logistic regression model was applied to determine the variables independently associated with long COVID. To determine the best model, a stepwise selection method was employed, and the model's performance was assessed utilizing a Receiver Operating Characteristic Curve (ROC). The findings revealed a long COVID prevalence of 56.4% (2,386 cases), with men having a 36.46% (OR = 1,36 CI = 1,17-1,58) higher chance of developing long COVID compared to women. A prior diagnosis before vaccination increased by 22.30% (OR = 1,22 CI = 1,05-1,41). Additionally, the use of sedatives and alcohol was linked to increases of 24.50% (OR = 1,24 CI = 1,07-1,43) and 34.95% (OR = 1,34 CI = 1,02-1,75), respectively. Beneficiaries of social programs faced a 47.29% (OR = 1,47 CI = 1,27-1,70) higher, while individuals with comorbidities had a 33.47% (OR =1,33 CI = 1,20-1,48). Hospitalization significantly raised the likelihood of prolonged symptoms by 331.92% (OR = 4,31 CI = 2,53-7,87). Overall, various factors, including sedative and alcohol use, were factors associated with long COVID, whereas vaccination showed a positive impact, suggesting that association models can help healthcare professionals identify high-risk patients and tailor care effectively.},
}

Humans
Brazil/epidemiology
*COVID-19/epidemiology
Female
Male
Middle Aged
Prevalence
Adult
Cross-Sectional Studies
Aged
SARS-CoV-2/isolation & purification
Risk Factors
*Health Behavior
Young Adult
Adolescent
Sociodemographic Factors

@article {pmid41480529,
year = {2025},
author = {Escrivá, N and Moreno-Galarraga, L and Barado, E and Torres, MG and Fernández-Montero, A},
title = {Assessment of long COVID-19 symptoms and functional status: insights from a cross-sectional study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1715786},
pmid = {41480529},
issn = {2296-858X},
abstract = {This cross-sectional study examines the functional limitations of Long COVID (LC) in a clinically confirmed cohort (n = 220). We collected sociodemographic, clinical, and lifestyle data via a structured electronic form and assessed daily limitations using the Post-COVID-19 Functional Status (PCFS) scale. Linear models were used to evaluate the association between symptom burden and functional limitations and to identify symptom-specific predictors of impairment. Participants had a mean age of 44.8 years, and 80.5% were women. A dose-response pattern linked higher symptom counts with worse PCFS grades in the multivariable-adjusted model (β = 0.17; 95% CI 0.10-0.25; p < 0.001). In hierarchical models, fatigue, dizziness, and memory loss were independent predictors of greater functional limitations (crude β: fatigue 1.56; 95% CI 1.22-1.90; dizziness 1.08; 95% CI 0.81-1.34; and memory loss 1.26; 95% CI 0.97-1.55), cumulatively explaining 51.3% of the variance in functional limitations. In contrast, other common LC symptoms did not retain independent associations after adjustment. These findings highlight the value of simple symptom counts and targeted symptom profiles for risk stratification in primary care and occupational health and for planning rehabilitation and work ability assessment. Prospective studies should validate these indicators over time and explore the mechanisms linking neurocognitive and fatigue phenotypes with persistent disability.},
}

@article {pmid41480252,
year = {2025},
author = {Salas, RL and la Asunción, M and Vásquez-Soto, C and Orta-Visbal, K and Serrano, V and Villarreal, E and Sepúlveda, S and Montalvo, MJ and Nuñez, JA and Borja, J},
title = {Scoping review of the emerging definition of long COVID: implications for future research and clinical practice.},
journal = {Revista de salud publica (Bogota, Colombia)},
volume = {27},
number = {6},
pages = {122127},
pmid = {41480252},
issn = {2539-3596},
mesh = {Humans ; *COVID-19/complications/diagnosis ; *Terminology as Topic ; Biomedical Research ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID, Post-COVID19 syndrome and prolonged COVID-19, are concepts classified as the set of signs and symptoms that persist after an acute episode of COVID-19 disease.

OBJECTIVE: To describe what definitions have been published for the term "long COVID".

METHODS: The PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) was used as a base for a scoping review, as suggested by Joanna Briggs Institute. A search of databases, Medline via PubMed, Embase, SciELO and The Cochrane Library was undertaken. The data registry and synthesis of the results was carried out independently by two reviewers.

RESULTS: Following removal of duplicates, 896 articles were retrieved of which 91 met the eligibility principles and 51 of which included a definition. At least four characteristics of the definitions were identified: time or term, organs affected, symptoms and clinical manifestations.

CONCLUSIONS: The review identified many concepts and definitions of "long COVID". These findings show that there is lack of consensus on the definition of long COVID-19.},
}

Humans
*COVID-19/complications/diagnosis
*Terminology as Topic
Biomedical Research
SARS-CoV-2

@article {pmid41477577,
year = {2025},
author = {Müllenmeister, C and Königs, G and Heinemann, S and Schröder, D and Müller, F and Hummers, E and Stölting, A and Happle, C and Dopfer-Jablonka, A and Behrens, G and Marotzki, U and Schmachtenberg, T},
title = {Acceptability of Telehealth-Delivered Occupational Therapy Among Individuals With Long COVID Using the Theoretical Framework of Acceptability: A Qualitative Study.},
journal = {International journal of telemedicine and applications},
volume = {2025},
number = {},
pages = {8879520},
pmid = {41477577},
issn = {1687-6415},
abstract = {BACKGROUND: Long COVID still challenges healthcare systems worldwide. Tailored treatments are scarce. In the ErgoLoCo study, we have developed and tested a telehealth-delivered occupational therapy intervention for people affected by long COVID. Acceptability from both recipients and providers is a prerequisite for implementing such new interventions.

AIM: This study is aimed at exploring the perceptions of people with long COVID and occupational therapists regarding the intervention's acceptability and telehealth delivery approaches.

METHODS: Semistructured interviews were conducted with 13 participants who experience long COVID and received the ErgoLoCo intervention delivered as teletherapy sessions or prerecorded videos. Eight occupational therapists who guided the teletherapy sessions participated in a focus group. Materials were analyzed following qualitative descriptive methods and interpreted using the theoretical framework of acceptability (TFA).

RESULTS: Occupational therapists and long COVID clients considered the occupational therapy approach a positive experience. While all participants in the teletherapy group found the occupational therapy approach helpful in coping with long COVID symptoms and regaining participation in meaningful occupations, perceptions varied in the group supplied with prerecorded videos. Some saw the intervention as helpful, but all emphasized the need for professional support from occupational therapists to use the program more effectively. The occupational therapists emphasized the need to tailor the therapy content to clients' needs to ensure effective and successful management of occupational challenges.

DISCUSSION: The study highlights telehealth-delivered occupational therapy's potential benefits and challenges for individuals with long COVID. It contributes to understanding the challenges and potential of telehealth-delivered occupational therapy for long COVID rehabilitation. This study's key finding is the importance of personalized and professionally guided telehealth interventions. Trial Registration: German Clinical Trial Registry identifier DRKS00029990.},
}

@article {pmid41404772,
year = {2025},
author = {Van Patten, R and Keatley, E},
title = {Cognitive rehabilitation for functional neurological disorder.},
journal = {CNS spectrums},
volume = {31},
number = {1},
pages = {e1},
doi = {10.1017/S1092852925100825},
pmid = {41404772},
issn = {1092-8529},
mesh = {Humans ; *Nervous System Diseases/rehabilitation/psychology/complications ; *Conversion Disorder/rehabilitation/psychology ; Cognitive Dysfunction/rehabilitation ; *Cognitive Behavioral Therapy/methods ; Cognitive Training ; },
abstract = {Cognitive problems represent one of the most common symptom dimensions in functional neurological disorder (FND; >80% of patients) and are frequently associated with distress, disability, and difficulties engaging in evidence-based treatments such as psychotherapy. Cognitive difficulties occur across the FND subtypes (eg, seizures, movement disorders, dizziness) but are largely underrecognized and undertreated by healthcare providers. That is, although a variety of interventions are available for primary functional symptoms and mental health comorbidities, there have not been any systematic efforts to date to specifically target cognitive functioning in FND, leaving an important gap in the literature.Cognitive rehabilitation is a flexible approach utilizing diverse techniques aimed at improving cognition and enhancing functional independence in people with neuropsychiatric disorders. Cognitive rehabilitation can have positive impacts (moderate effect sizes) on cognition and everyday functioning across a variety of conditions, including traumatic brain injury, mild cognitive impairment, long COVID, PTSD, and others. Given the transdiagnostic clinical utility of cognitive rehabilitation, it has potential for benefit in many patients with FND if adapted and applied appropriately.In this review, we highlight the utility of cognitive rehabilitation for FND, with a focus on clinically actionable advice and guidance. We describe fundamental principles of cognitive rehabilitation, evidence for its efficacy and effectiveness across neuropsychiatric disorders, and methods for avoiding potential pitfalls when applying it in FND. We then discuss a Case Vignette in order to emphasize the application of cognitive rehabilitation principles in an individual patient. We conclude with future directions for research and clinical care.},
}

Humans
*Nervous System Diseases/rehabilitation/psychology/complications
*Conversion Disorder/rehabilitation/psychology
Cognitive Dysfunction/rehabilitation
*Cognitive Behavioral Therapy/methods
Cognitive Training

@article {pmid41477078,
year = {2025},
author = {Agarwal, K and Tansey, CM and Rizk, AK and Beauchamp, MK and Ross, BA and Bourbeau, J and Sedeno, M and Barreto, L and Zucco, R and Crowley, E and Janaudis-Ferreira, T},
title = {Perspectives of Individuals With Long COVID on Virtual Physical Rehabilitation: A Qualitative Study.},
journal = {Archives of rehabilitation research and clinical translation},
volume = {7},
number = {4},
pages = {100526},
pmid = {41477078},
issn = {2590-1095},
abstract = {OBJECTIVE: Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2, and long COVID is a chronic condition characterized by symptoms persisting for atleast 3 months after infection. To explore the perspectives of individuals with long COVID after an 8-week virtual physical rehabilitation program.

DESIGN: Qualitative descriptive study.

SETTING: Clinics and research cohorts.

PARTICIPANTS: Adults (n=132) with confirmed or probable COVID-19 infection and persistent symptoms, including reduced mobility, muscle weakness, dyspnea, and/or fatigue, were recruited in a randomized controlled trial. Thirteen intervention group participants who completed the rehabilitation program were included in this qualitative study.

INTERVENTIONS: The intervention group (n=65) received 8 weeks of tailored, symptom-titrated exercises, weekly educational sessions, and usual care, whereas the control group (n=67) received only usual care.

MAIN OUTCOME MEASURES: Semistructured videoconference interviews were conducted and analyzed using deductive thematic analysis.

RESULTS: Participants' age (mean ± SD) was 48.3±15.6 years, 6 had been hospitalized during their COVID-19 infection, and the duration of long COVID (mean ± SD) was 18.8±7.2 months. Four themes were identified: (1) Motivation and confidence: most participants expressed confidence in joining the program, motivated by health goals, scientific contribution, and reassurance from professional support. (2) Program features: the program was praised for its well-organized format, ideal duration, convenient scheduling, supportive kinesiologists, and individualized exercise plans. (3) Health effects: while most reported physical and emotional improvements (eg, increased energy, mobility, and confidence), some noted challenges upon returning to work. (4) Post-program suggestions: participants intended to continue exercising but faced barriers such as fatigue and a lack of motivation, highlighting the need for continued support and resources to maintain progress.

CONCLUSIONS: This study highlights the positive effects and relevant challenges associated with completing an 8-week personalized, symptom-titrated virtual physical rehabilitation program for individuals with long COVID, emphasizing the need for tailored support and ongoing resources to facilitate sustained recovery.},
}

@article {pmid41476972,
year = {2025},
author = {Del Carpio-Orantes, L and Zambrano-Sánchez, G},
title = {Vaccination in the post-COVID era: lessons to be learned in Latin America.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1726836},
pmid = {41476972},
issn = {1664-3224},
mesh = {Humans ; Latin America/epidemiology ; *COVID-19/prevention & control/epidemiology/immunology ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Vaccination ; },
abstract = {In this document we discuss the reality of COVID vaccination in Latin America, which has been uneven across the continent; however, some experiences with COVID vaccination have demonstrated a protective effect against the development of chronic manifestations of COVID, in the so-called post-COVID syndrome.},
}

Humans
Latin America/epidemiology
*COVID-19/prevention & control/epidemiology/immunology
*COVID-19 Vaccines/immunology/administration & dosage
*SARS-CoV-2/immunology
*Vaccination

@article {pmid41476195,
year = {2025},
author = {Yeh, HW and Chaou, CH and Yang, SF and Wang, YH and Kuan, YH and Yeh, CB},
title = {SGLT2 inhibitors prevent long-COVID-associated cognitive and pain symptoms in type 2 diabetes patients.},
journal = {Virology journal},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12985-025-03054-5},
pmid = {41476195},
issn = {1743-422X},
support = {CSH-2025-D-005//Chung Shan Medical University Hospital/ ; },
abstract = {BACKGROUND: Long COVID presents significant health challenges, especially for patients with type 2 diabetes. Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors may provide protective effects against COVID-19 complications, but their role in reducing long COVID risk remains unclear.

METHODS: Utilizing the TriNetX platform, a retrospective cohort study was conducted among adults with type 2 diabetes diagnosed with COVID-19 between January 1, 2020, and June 30, 2024. Propensity score matching balanced demographic, clinical, and comorbidity profiles between SGLT2 inhibitor users and non-users. Cox proportional hazards regression assessed the risk of long COVID, defined by a spectrum of post-COVID-19 conditions.

RESULTS: Among 5,162 matched pairs, SGLT2 inhibitor use was associated with a significantly lower risk of long COVID (HR = 0.85, 95% CI: 0.79-0.91). In the category of long-COVID symptoms such as abdominal symptoms, anxiety/depression, pain, headache, and cognitive symptoms, there were lower risks observed in the SGLT2 inhibitor group. Subgroup analyses showed consistent risk reduction across different age groups and sexes.

CONCLUSIONS: SGLT2 inhibitor use in patients with type 2 diabetes was linked to a reduced risk of long COVID. These findings suggest potential therapeutic benefits beyond glycemic control and highlight the need for further investigation into SGLT2 inhibitors as part of post-COVID-19 management strategies.},
}

@article {pmid41272653,
year = {2025},
author = {Liu, B and Zhu, X and Ying, Y and Li, L and Zhou, H and Xu, Z and Wang, F and Jiang, L},
title = {Impact of COVID-19 lived experiences on future influenza pandemic worry: a cross-sectional survey in China.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {4405},
pmid = {41272653},
issn = {1471-2458},
support = {LGF22G030018//Zhejiang Province Public Welfare Technology Application Research Project/ ; 2023S027//Key Project of Ningbo Public Welfare Research Plan/ ; },
abstract = {BACKGROUND: Against the backdrop of repeated warnings regarding the inevitability of future influenza pandemics and the critical importance of public preparedness, the aim of this study was to explore public worry about a future influenza pandemic and its influencing factors in the post-coronavirus disease 2019 (COVID−19) era, particularly focusing on the role of lived experiences during the COVID−19 pandemic.

METHODS: An online cross-sectional study was conducted between October and December 2024. Overall, 1254 valid samples were finally included. Descriptive analysis and hierarchical logistic regression were performed to examine the associations between potential influencing factors and public worry about a future influenza pandemic.

RESULTS: Approximately 48.49% of the participants reported being worried about a future influenza pandemic. The final model of hierarchical logistic regression revealed that sex, educational level, having one or more children in the family, lived experiences (repeated infections, long-COVID, medical resource shortages), and risk perceptions (perceived likelihood and severity) were associated with worry about a future influenza pandemic.

CONCLUSION: This study reveals that lived experiences during the COVID−19 pandemic are associated with increased worry about a future influenza pandemic by the public. The factors identified can be used to guide the development of evidence-based risk communication and preparedness strategies to foster public participation. Crucial baseline data were also provided from a specific period to monitor changes in public perceptions of influenza pandemic threats over time.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25704-7.},
}

@article {pmid41474983,
year = {2025},
author = {Zhang, TM and Sharp, SP and Scott, JD and Taren, D and Samaniego, JC and Unger, ER and Bertolli, J and Lin, JS and Ramers, CB and Godino, JG},
title = {Characterization of Post-Viral Infection Behaviors Among Patients With Long COVID: Prospective, Observational, Longitudinal Cohort Analyses of Fitbit Data and Patient-Reported Outcomes.},
journal = {JMIR formative research},
volume = {9},
number = {},
pages = {e77644},
doi = {10.2196/77644},
pmid = {41474983},
issn = {2561-326X},
mesh = {Humans ; *Patient Reported Outcome Measures ; Female ; Male ; Longitudinal Studies ; Prospective Studies ; *COVID-19/psychology/complications/physiopathology ; Middle Aged ; *Exercise/physiology ; Adult ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/physiopathology/psychology ; Aged ; Post-Acute COVID-19 Syndrome ; *Fitness Trackers ; Wearable Electronic Devices ; },
abstract = {BACKGROUND: Long COVID encompasses a range of health problems that can be highly debilitating. While some research has relied on self-reported measures of symptoms and functioning, few studies have characterized symptoms in relation to behaviors and physiology measured objectively through wearable devices.

OBJECTIVE: The primary aim of this study was to identify longitudinal patterns in physical activity, physiology, and patient-reported outcomes (PROs) among patients with long COVID at a Federally Qualified Health Center in the United States. The secondary aim was to identify meaningful subgroups or phenotypes within this cohort and examine how PROs and symptoms overlay with physical activity characteristics.

METHODS: This was a prospective, observational, longitudinal cohort study recruiting a subset of low-income patients enrolled in the Long COVID and Fatiguing Illness Recovery Program. From March 2022 to May 2023, a total of 172 patients with long COVID or myalgic encephalomyelitis/chronic fatigue syndrome were given Fitbit Charge 5 (Fitbit Inc) devices and instructed to wear them continuously for up to a year. Patients completed PRO questionnaires (PROMIS-29 [Patient-Reported Outcomes Measurement Information System-29] and symptom questionnaires, etc) at baseline, 3, and 6 months. Inclusion in longitudinal analysis required at least 20 hours of valid wear data per day for a minimum of 7 days. The World Health Organization guideline on moderate to vigorous physical activity (MVPA) was used to differentiate MPVA-active and MVPA-inactive patients. Linear mixed effects regression was performed to assess longitudinal associations between physical activity levels and PROs.

RESULTS: Among 172 patients, 80.2% (n=138) were female, 75.6% (n=130) were White, 45.3% (n=78) were unemployed, and 94.8% (n=163) had estimated annual income below US $50,000. Of these patients, 82 (47.7%) met valid wear criteria, providing 50.5 days of Fitbit data on average. At baseline, MVPA-inactive patients (n=41) reported statistically more severe problems regarding physical function, fatigue, and dyspnea than MVPA-active patients (n=41) on both continuous and categorical scales, with P<.05 from both Student t tests (2-tailed) and chi-squared tests. Longitudinal analysis found that MVPA-inactive patients showed a decreased ability to participate in social roles (estimated group difference=-4.21 T-score points over 3 months, 95% CI -6.64 to -1.78, P<.001) and a higher intensity of sleep symptoms (estimated group difference=2.06 severity score points over 3 months, 95% CI 0.40 to 3.71, P=.02) over time.

CONCLUSIONS: This study showed that patients with long COVID could remain MVPA-active despite experiencing symptoms. These findings provide insights into the relationship between PROs, physical activity, and long COVID, which suggests the importance of considering individual activity profiles when tailoring treatment plans, especially in a low-income population. The findings of this study should be interpreted as hypothesis-generating, considering its exploratory nature and limitations, including high attrition rates and missing data.},
}

Humans
*Patient Reported Outcome Measures
Female
Male
Longitudinal Studies
Prospective Studies
*COVID-19/psychology/complications/physiopathology
Middle Aged
*Exercise/physiology
Adult
SARS-CoV-2
*Fatigue Syndrome, Chronic/physiopathology/psychology
Aged
Post-Acute COVID-19 Syndrome
*Fitness Trackers
Wearable Electronic Devices

@article {pmid41474066,
year = {2026},
author = {Vitiello, A},
title = {Long Covid Syndrome and Role of Autonomic Nervous System.},
journal = {Reviews in medical virology},
volume = {36},
number = {1},
pages = {e70101},
doi = {10.1002/rmv.70101},
pmid = {41474066},
issn = {1099-1654},
}

@article {pmid41472279,
year = {2025},
author = {Strumiliene, E and Malinauskiene, L and Urboniene, J and Jurgauskienė, L and Zablockienė, B and Jancoriene, L},
title = {Clinical and Immunological Recovery Trajectories in Severe COVID-19 Survivors: A 12-Month Prospective Follow-Up Study.},
journal = {Viruses},
volume = {17},
number = {12},
pages = {},
doi = {10.3390/v17121610},
pmid = {41472279},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/immunology ; Male ; Female ; Middle Aged ; Prospective Studies ; Follow-Up Studies ; Adult ; SARS-CoV-2/immunology ; Aged ; Survivors ; Fatigue ; Killer Cells, Natural/immunology ; Lymphocyte Subsets/immunology ; Dyspnea ; Immunoglobulins/blood ; },
abstract = {Background: The link between clinical recovery and immune restoration after severe COVID-19 remains poorly defined. Although most survivors experience symptomatic improvement, persistent symptoms have been hypothesized to reflect ongoing immune dysregulation. Methods: This prospective cohort study followed 93 unvaccinated adults with RT-PCR-confirmed moderate-to-critical COVID-19 at 3, 6, and 12 months post-discharge. Clinical assessments used structured interviews to evaluate the persistent symptoms. Peripheral blood analyses were used to measure lymphocyte subsets, immunoglobulins, and complement components. Results: Clinical recovery was substantial; fatigue prevalence declined from 70.9% to 24.7% and dyspnea prevalence from 81.7% to 25.8% by 12 months (p < 0.001 for both). However, immune recovery exhibited divergent patterns. Activated T cells (CD3[+]HLA-DR[+]) decreased significantly (from 20% to 13%; p < 0.001), complement C3c levels paradoxically increased from 1.23 to 1.35 g/L (p < 0.001), and serum IgA increased by 32% (p = 0.003). NK cells remained stable overall but were persistently reduced in a subset (~25%) of patients, particularly among those with fatigue and dyspnea. Critical illness was associated with slower T-cell resolution, prolonged IgM elevation, and increased complement activity. Conclusions: One year after hospitalization, most patients achieved substantial clinical improvement, but immune reconstitution lagged behind. These findings highlight the dissociation between clinical and immunological recovery and suggest that persistent immune dysregulation may be associated with long COVID manifestations. Incorporating immune monitoring into post-COVID care may help identify patients at risk of prolonged sequelae and guide targeted therapeutic strategies.},
}

Humans
*COVID-19/immunology
Male
Female
Middle Aged
Prospective Studies
Follow-Up Studies
Adult
SARS-CoV-2/immunology
Aged
Survivors
Fatigue
Killer Cells, Natural/immunology
Lymphocyte Subsets/immunology
Dyspnea
Immunoglobulins/blood

@article {pmid41472222,
year = {2025},
author = {Bhargava, A and Patel, H and Szpunar, S and Sharma, M and Somero, M and Moudgil, S and Saravolatz, L},
title = {Fatigue Severity, Cognitive Strain, and Psychological Health in Long COVID: Untangling the Interconnected Aftermath from a Dedicated Long COVID Clinic.},
journal = {Viruses},
volume = {17},
number = {12},
pages = {},
doi = {10.3390/v17121551},
pmid = {41472222},
issn = {1999-4915},
support = {Medical staff funds//Henry Ford Hospital/ ; },
mesh = {Humans ; *Fatigue/psychology/etiology ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; Prospective Studies ; Depression/etiology ; Aged ; *Cognitive Dysfunction/etiology/psychology ; Severity of Illness Index ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; *Mental Health ; Surveys and Questionnaires ; },
abstract = {Post-acute sequelae of SARS-CoV-2 infection (PASC) frequently includes persistent fatigue and cognitive dysfunction, but the relationship between these symptoms remains poorly defined. In this prospective observational study at the Henry Ford St. John Long COVID Clinic (LCC) from July 2023 to March 2025, we assessed fatigue severity using the Fatigue Assessment Scale (FAS) and examined its relationship with depression and cognitive symptoms. New patients completed demographic and clinical questionnaires, Patient Health Questionnaire (PHQ)-9, and Montreal Cognitive Assessment (MoCA) at their first LCC visit. Among 41 patients, 35 (85.4%) met the inclusion criteria for fatigue (FAS ≥ 22), with 18 (51.5%) experiencing severe fatigue (FAS > 34). Severe fatigue was significantly associated with shortness of breath, chest pain, and depression. Patients experiencing severe fatigue had significantly higher median PHQ-9 scores (12.5) compared to those with mild to moderate fatigue (5.0, p < 0.001). However, there were no significant differences in MoCA scores between these groups. Our study suggests a strong relationship between fatigue and depression in patients with PASC, emphasizing the importance of integrated physical and psychological healthcare. Moreover, since cognitive performance does not vary with fatigue levels, all PASC patients with cognitive dysfunction should receive routine cognitive screenings, regardless of the severity of their fatigue.},
}

Humans
*Fatigue/psychology/etiology
*COVID-19/psychology/complications
Male
Female
Middle Aged
Prospective Studies
Depression/etiology
Aged
*Cognitive Dysfunction/etiology/psychology
Severity of Illness Index
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Adult
*Mental Health
Surveys and Questionnaires

@article {pmid41470215,
year = {2025},
author = {Macej, M and Grus, C and Čuj, J and Demjanovič Kendrová, L and Mikuľaková, WB and Kubincová, A and Takáč, P},
title = {Quality of Life and Functional Status in Individuals with Persistent Post-COVID Symptoms: A Cross-Sectional Comparison by Reported Rehabilitation.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {12},
pages = {},
pmid = {41470215},
issn = {1648-9144},
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Quality of Life/psychology ; *COVID-19/rehabilitation/complications/psychology ; Adult ; Middle Aged ; *Functional Status ; Surveys and Questionnaires ; SARS-CoV-2 ; },
abstract = {Background and Objectives: Post-COVID-19 condition (PCC, long COVID) is associated with persistent symptoms and marked reductions in health-related quality of life (HRQoL), but real-world data on rehabilitation and everyday functioning remain limited. Materials and Methods: In a cross-sectional online survey conducted between 15 April and 15 May 2024, we analysed 406 adults (308 women; mean age 36.0 ± 12.1 years) with ongoing post-COVID symptoms recruited from two moderator-supervised support communities. The questionnaire included sociodemographic and clinical items, the 36-Item Short Form Health Survey (SF-36) and the Post-COVID-19 Functional Status (PCFS) scale. Participants indicated whether they had completed any form of rehabilitation targeting post-COVID problems (yes/no). Group differences were examined using Welch's t-test, Mann-Whitney U and χ[2] tests, as appropriate. Multiple linear regression models with Bonferroni correction were used to explore associations between rehabilitation status, age, sex, symptom duration and outcomes. Results: Overall, 182 respondents (44.8%) reported rehabilitation and 224 (55.2%) did not. The groups did not differ significantly in age, sex distribution, BMI, number of infections, symptom duration or hospitalisation history. Most SF-36 domains, component summaries and PCFS differed significantly between groups, with small-to-large effects favouring respondents who reported rehabilitation. The largest effect sizes were observed for Vitality and Mental Health, whereas Physical Functioning showed no clear difference. In multivariable models, older age and longer symptom duration were consistently associated with poorer HRQoL, while rehabilitation status remained a robust correlate of better scores in several SF-36 domains, both component summaries, perceived health, and lower PCFS grades after correction for multiple testing. Conclusions: Although the cross-sectional design, self-reported data and non-standardised rehabilitation exposure preclude causal inference, the findings highlight the substantial HRQoL and functional burden of long COVID and suggest that, within a symptomatic population, reported completion of rehabilitation is positively associated with multiple aspects of everyday health and functioning.},
}

Humans
Female
Male
Cross-Sectional Studies
*Quality of Life/psychology
*COVID-19/rehabilitation/complications/psychology
Adult
Middle Aged
*Functional Status
Surveys and Questionnaires
SARS-CoV-2

@article {pmid41470138,
year = {2025},
author = {Septiana, M and Kaswandani, N and Yuniar, I and Iskandar, ATP and Puspitasari, HA and Satari, HI},
title = {Pulmonary Function and Associated Prognostic Factors in Children After COVID-19: A Retrospective Cohort Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {12},
pages = {},
pmid = {41470138},
issn = {1648-9144},
mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Comorbidity ; *COVID-19/physiopathology/complications/epidemiology ; *Lung/physiopathology ; Prevalence ; Prognosis ; Respiratory Function Tests ; Retrospective Studies ; Spirometry ; },
abstract = {Background and Objectives: Reports of respiratory function in COVID-19 survivors are still rare, especially in children. This study aims to determine the prevalence and prognostic factors that influence long-term respiratory function in children after COVID-19. Materials and Methods: An observational analytical study with a retrospective cohort design was conducted between January and June 2024. The subjects were pediatric patients aged 5-18 years with confirmed history of COVID-19. Respiratory function was evaluated with spirometry. The analyzed prognostic factors included clinical classification of COVID-19, gender, age, comorbidities, history of ventilator support, history of hospitalization and persistent symptoms. Results: A total of 100 subjects were included in this study. The subjects were 53% female, 52% aged ≥ 12-18 years, and 76% had at least one comorbidity, the most common being obesity (27%). The majority (73%) had a history of mild COVID-19, and 78% were not hospitalized. The prevalence of impaired lung function was 47%, dominated by restrictive lung pattern. The prevalence of long COVID was 18%, with the most common symptom being fatigue (13%). The presence of persistent symptom is significantly associated with abnormal spirometry result (p = 0.03, RR 1.99; 95% CI 1.38-2.87). Undernourished status and moderate-to-severe and critical COVID-19 significantly influence long-term respiratory function with p = 0.002, aOR 5.64; CI 95% 1.89-16.85 and p = 0.006, aOR 5.18; and CI 95% 1.59-16.89, respectively. Conclusions: The prevalence of impaired lung function in children after COVID-19 was 47%. Persistent symptoms, undernourished status, and moderate-to-critical severity of COVID-19 were found to be associated with impaired long-term respiratory function in post-COVID-19 pediatric patients. Further prospective studies are needed to confirm these findings and clarify causal mechanisms.},
}

Adolescent
Child
Child, Preschool
Female
Humans
Male
Comorbidity
*COVID-19/physiopathology/complications/epidemiology
*Lung/physiopathology
Prevalence
Prognosis
Respiratory Function Tests
Retrospective Studies
Spirometry

@article {pmid41469619,
year = {2025},
author = {Braig, S and Peter, RS and Nieters, A and Kräusslich, HG and Brockmann, SO and Göpel, S and Merle, U and Steinacker, JM and Kern, WV and Rothenbacher, D and , },
title = {Post-Covid-19 symptoms, subjective work ability and sick leave 2 years after acute infection-results from a population-based long COVID study.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-025-26066-w},
pmid = {41469619},
issn = {1471-2458},
abstract = {BACKGROUND: The post-COVID syndrome (PCS) is associated with reduced work ability, increased sick leave and delayed return to work. Yet, the relationship is complex due to a heterogeneous set of PCS symptoms and the multifaceted nature of work ability.

METHODS: Based on a population-based longitudinal study (n = 5422, 18-65 years) conducted in the Southwest of Germany, we describe the evolution of work ability (mWAI1), task-related work ability (mWAI2), and sick leave 6-12 and 24 months after a SARS-CoV-2 index infection and confirmed by Polymerase Chain Reaction. Descriptive analyses on mWAI1 and mWAI2 and adjusted linear regression analyses were performed.

RESULTS: 1.1% of our population was continuously on sick leave since the initial SARS-CoV-2 infection (about 24 months after the infection). Pre-infection mWAI1 was not regained due to persisting or newly occurring symptoms of fatigue, neurocognitive impairment and anxiety/depression/sleep disorders that were related also to lower mWAI2. Effect modifiers of the associations between risk factors and mWAI1 or mWAI2 were age, working tasks, and comorbid mental conditions. Further SARS-CoV-2 infections were associated with poorer mWAI2 in physically (regression coefficient, 95% confidence intervals: -3.45 (-6.15,-0.74) but not mentally working participants (0.20 (-0.54,0.95)) and age proved to be a stronger risk factor for mWAI2 in physically working subjects.

CONCLUSIONS: We confirmed known risk factors but further emphasized effect modifiers like working task or comorbid mental disorders for work ability and described variables related to sick leave after SARS-CoV-2 infection.},
}

@article {pmid41467074,
year = {2025},
author = {Hendrickson, RC and Cheah, CS and Tai, ML and Pagulayan, KF and Liang, KJ and McCall, CA and Schindler, AG and Hart, KL and Rosser, AF and Oakley, JC},
title = {Impact of Prior History of Traumatic Stress on Autonomic and Multi-System Symptoms Following COVID-19 Infection.},
journal = {Chronic stress (Thousand Oaks, Calif.)},
volume = {9},
number = {},
pages = {24705470251407210},
doi = {10.1177/24705470251407210},
pmid = {41467074},
issn = {2470-5470},
abstract = {BACKGROUND: Persistent symptoms of autonomic dysregulation are common after COVID-19 infection and may result from alterations in central and/or peripheral autonomic regulatory processes. Traumatic stress can cause persistent alterations in autonomic function, potentially changing the response to future traumatic or physiologic stressors. However, the relationship between prior history of traumatic stress and autonomic symptom burden after COVID-19 infection has not been explored.

OBJECTIVES: Examine the potential for additive and/or interactive effects of traumatic stress and COVID-19 infection on autonomic symptom burden, and compare this with other common post-acute sequelae of COVID-19 (PASC) symptom domains.

DESIGN: Observational, self-report, single time-point online assessment.

PARTICIPANTS: 404 United States adults with (N = 289) and without (N = 112) a self-reported history of COVID-19 infection.

MAIN OUTCOMES AND MEASURES: Autonomic symptom burden (Composite Autonomic Symptom Score [COMPASS 31]), lifetime traumatic stressors (Life Events Checklist), posttraumatic stress disorder (PTSD Checklist-5), self-reported neurocognitive functioning (Neuro-QoL), insomnia (Insomnia Severity Index), and fatigue and pain (PROMIS Fatigue and Pain Interference measures).

RESULTS: Autonomic symptom burden was significantly and positively related to both history of COVID-19 infection and number of probable lifetime traumatic stressors, with probable lifetime traumatic stressors functioning as a positive moderator of the relationship between history of COVID-19 infection and autonomic symptom burden (Cohen's partial f[2 ]= .11, .07 and .02 for COVID history, trauma history and interaction term respectively, all p < .05, in a model also including age and gender). The moderation effect remained significant when adjusting for both current PTSD symptoms and pre-existing multi-system PASC-like symptoms prior to COVID-19. History of traumatic stress and of COVID-19 infection each had significant and positive associations with other PASC symptom domains, but with domain-specific patterns.

CONCLUSIONS AND RELEVANCE: Prior history of traumatic stress has a positive and interactive effect on symptoms of autonomic dysregulation following COVID-19 infection, independent of PTSD symptoms. This suggests that exposure to traumatic stress may affect the response to future stressors, including physiologic stressors such as COVID-19 infection, through persistent changes in stress-threat response systems. This relationship may provide a physiologic explanation for prior observations that baseline anxiety prior to COVID-19 infection is associated with increased likelihood of PASC.},
}

@article {pmid41466718,
year = {2025},
author = {Kenny, TA},
title = {Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.},
journal = {Therapeutic advances in drug safety},
volume = {16},
number = {},
pages = {20420986251395925},
doi = {10.1177/20420986251395925},
pmid = {41466718},
issn = {2042-0986},
abstract = {The COVID-19 pandemic has renewed attention to complex chronic health conditions that challenge conventional biomedical paradigms. Syndromes such as postural orthostatic tachycardia syndrome and myalgic encephalomyelitis/chronic fatigue syndrome have gained broader visibility through the lens of Long COVID. As global vaccination campaigns expanded, a subset of individuals began reporting similarly persistent, multisystem symptoms following COVID-19 immunization-informally referred to as post-COVID-19 vaccination syndrome. These presentations, which include dysautonomia, neuropathic pain, post-exertional malaise, and cognitive dysfunction, resemble post-infectious syndromes and may involve shared immune-related mechanisms. Although no causal relationship to vaccination has been established, these cases-together with comparable reports following other vaccines-highlight limitations in current vaccine safety systems for detecting and evaluating complex chronic outcomes. This article introduces the concept of complex chronic adverse events following immunization (CC-AEFIs) as a pragmatic, surveillance-oriented framework to support the systematic identification and investigation of such cases. CC-AEFIs are not syndromic diagnoses but a higher-order category encompassing persistent, multifactorial conditions that may follow immunization yet challenge existing pharmacovigilance definitions and tools. These conditions often involve multiple organ systems, delayed onset, fluctuating trajectories, diagnostic ambiguity, and symptom heterogeneity. Drawing on the author's lived experience as an affected patient and integrating clinical, regulatory, and experiential evidence, the analysis examines structural and epistemic limitations across the pharmacovigilance continuum-from underrecognition in clinical settings to analytic exclusion and constrained governance. It concludes by proposing reforms to strengthen safety-system responsiveness, including enhanced diagnostic training, longitudinal surveillance, patient-reported outcome integration, and analytic transparency. Addressing these limitations is essential to sustain public trust, ensure equitable care, and uphold the scientific integrity of immunization programs.},
}

@article {pmid41466608,
year = {2025},
author = {de Bruijn, S and Huiberts, AJ and Andeweg, SP and Hoeve, CE and Schipper, M and Grobbee, DE and de Melker, HE and van de Wijgert, JHHM and van den Hof, S and Knol, MJ and van den Wijngaard, CC},
title = {Post-COVID-19 condition in individuals infected with SARS-CoV-2 in autumn 2023 in the Netherlands: a prospective cohort study with pre- and post-infection data.},
journal = {The Lancet regional health. Europe},
volume = {59},
number = {},
pages = {101472},
doi = {10.1016/j.lanepe.2025.101472},
pmid = {41466608},
issn = {2666-7762},
abstract = {BACKGROUND: Post-COVID-19 condition (PCC) risk may have changed due to vaccination status, virus variants, prior infections, and other factors. We aimed to estimate PCC prevalence for one year in individuals infected with SARS-CoV-2 during autumn 2023, controlling for pre-infection symptoms and prevalence in recently uninfected participants.

METHODS: VASCO, a Dutch ongoing prospective cohort, collects three-monthly questionnaires and six-monthly SARS-CoV-2 serology. Participants indicated severity of 23 symptoms on a five-point Likert scale, and of fatigue and concentration problems on the Checklist Individual Strength. We matched participants who did with those who did not report a SARS-CoV-2 infection between September 25, 2023 and January 7, 2024, and censored follow-up time for both upon serological or antigen test evidence of infection. We estimated PCC-prevalence as the excess prevalence of at least one PCC-related symptom between matched infected and uninfected participants at 90, 180, 270, and 360 days post-infection. Additionally, participants could self-attribute long-term symptoms to SARS-CoV-2.

FINDINGS: We 1:1 matched 5621 infected to 5621 uninfected participants. The PCC prevalence, estimated as the marginal mean excess prevalence of PCC-related symptoms between infected and uninfected participants, was 0.2% (95% confidence interval: -1.9 to 2.3, p = 0.84) at 90 days, 0.5% (-1.6 to 2.6, p = 0.63) at 180 days, 0.7% (-1.3 to 2.8, p = 0.48) at 270 days, and 0.0% (-2.1 to 2.1, p = 0.99) at 360 days. Excess prevalence of new mild and severe long-term symptoms self-attributed to SARS-CoV-2 between infected and uninfected participants were both elevated at 90 days (mild: 7.2% (5.1-9.2), severe: 0.6% (0.4-0.8)) and 180 days (mild: 3.2% (2.0-4.4), severe: 0.3% (0.2-0.4)) post-infection (all p-values <0.0001), but no longer thereafter.

INTERPRETATION: This double-controlled study, incorporating pre- versus post-infection and uninfected symptom data, found a low risk of PCC among a community-dwelling adult population infected during the autumn 2023 SARS-CoV-2 wave. The prevalence of PCC-related symptoms in infected and uninfected individuals was not significantly different at 90-360 days post-infection. The excess prevalences of self-attributed long-term symptoms were elevated at 90 and 180 days post-infection but no longer from 270 days onwards. These findings suggest that the 2023 wave inferred a lower PCC risk than during the pandemic period.

FUNDING: Funded by the Dutch Ministry of Health, Welfare and Sport.},
}

@article {pmid41465566,
year = {2025},
author = {Khodanovich, M and Kamaeva, D and Usova, A and Pashkevich, V and Moshkina, M and Obukhovskaya, V and Kataeva, N and Levina, A and Tumentceva, Y and Shadrina, M and Ranzaeva, A and Vasilieva, S and Schastnyy, E and Naumova, A and Svetlik, M},
title = {Demyelination and Cognitive Performance in Long COVID Patients with Insomnia and/or Depression.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262412141},
pmid = {41465566},
issn = {1422-0067},
support = {22-15-00481-П//Russian Science Foundation/ ; },
mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/complications/etiology ; Male ; Female ; *COVID-19/complications/psychology ; Middle Aged ; *Depression/complications/etiology ; *Demyelinating Diseases/etiology/diagnostic imaging ; Magnetic Resonance Imaging ; Adult ; *Cognition ; SARS-CoV-2 ; Biomarkers/blood ; *Cognitive Dysfunction/etiology ; Case-Control Studies ; Neuropsychological Tests ; White Matter/diagnostic imaging/pathology ; Aged ; },
abstract = {Insomnia and depression are severe sequelae of COVID-19 and often occur simultaneously. Our study examined associations of insomnia and/or depression with cognitive impairments, white matter changes, and serum biomarkers. In total, 76 long COVID patients and 22 healthy controls were examined using neuropsychiatric (ISI, HADS, and HDRS) and cognitive (MoCA, Stroop, WMT, and TMT) tests, with their blood biomarkers (anti-SARS-CoV-2, BDNF, anti-S100, anti-MBP, and anti-PLP) investigated, and underwent MRI using macromolecular proton fraction (MPF) mapping to quantify myelination. The Insomnia (n = 14), Depression (n = 12), InsDep (comorbid insomnia-depression, n = 13), and PostCovid (long COVID without depression and insomnia, n = 32) groups were identified based on psychiatric/neurological diagnoses and neuropsychiatric assessment. Cognitive performance was most affected in the Insomnia group in the MoCA and CW Stroop tests. The Depression group underperformed in the TMT and W Stroop task; the InsDep group underperformed in the WMT. The Insomnia group showed the greatest demyelination, affecting commissural (CC and tapetum), projection (CR, IC, CST, cerebral peduncles, CP, and ML), and some association pathways (SLF, SFOF), as well as most juxtacortical regions, the thalamus, and the midbrain; these changes correlated with insomnia severity. The Depression and InsDep groups showed smaller but significant overall demyelination correlated with depression severity. The Depression group exhibited the highest MPF decrease in the globus pallidus, putamen, and external capsule, while the InsDep group demonstrated the highest demyelination of the association pathways IFOF, UF, and cingulum. The anti-PLP levels were the highest in the Insomnia group and correlated with both the persistence of insomnia/depression symptoms and demyelination. Demyelination in long COVID is associated with high levels of myelin-specific autoantibodies, but symptoms of insomnia and/or depression are associated with demyelination of a different set of brain structures.},
}

Humans
*Sleep Initiation and Maintenance Disorders/complications/etiology
Male
Female
*COVID-19/complications/psychology
Middle Aged
*Depression/complications/etiology
*Demyelinating Diseases/etiology/diagnostic imaging
Magnetic Resonance Imaging
Adult
*Cognition
SARS-CoV-2
Biomarkers/blood
*Cognitive Dysfunction/etiology
Case-Control Studies
Neuropsychological Tests
White Matter/diagnostic imaging/pathology
Aged

@article {pmid41464688,
year = {2025},
author = {Miana, M and Moreta-Fuentes, C and Moreta-Fuentes, R and Varillas-Delgado, D and Jiménez-Antona, C and Laguarta-Val, S},
title = {Clinical Improvements Following a Non-Aerobic Therapeutic Exercise in Women with Long COVID.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248786},
pmid = {41464688},
issn = {2077-0383},
abstract = {Background/Objectives: Long COVID (LC) is characterized by persistent symptoms such as fatigue, pain, and reduced quality of life, often lasting months after acute infection. Exercise-based interventions have shown promise, but evidence for non-aerobic programs remains limited. This study aimed to evaluate the effects of a 12-week motor control exercise program on body composition and fatigue in women with LC and to explore associations with physical activity and psychosocial factors. Methods: An exploratory pre-post non-controlled intervention study was conducted in 17 women with LC symptoms persisting for over one year. Participants completed 24 individualized sessions of a non-aerobic therapeutic exercise program focused on trunk stabilization. Outcomes included body composition (bioimpedance analysis), fatigue (Modified Fatigue Impact Scale), health-related quality of life (EQ-5D-5L), physical activity (IPAQ), and kinesiophobia (TSK-11). Paired t-tests, effect sizes, correlations, and regression models were applied. Results: The intervention significantly reduced total body fat (37.09% to 35.41%, p < 0.001) and trunk fat (35.82% to 33.82%, p < 0.001), with large effect sizes. Physical and psychosocial fatigue improved markedly (MFIS physical: 29.71 to 21.06, p < 0.001; psychosocial: 6.00 to 4.29, p = 0.001), while cognitive fatigue showed non-significant change. Pain/discomfort scores decreased substantially (2.86 to 1.79, p < 0.001). Vigorous activity and walking time increased, and sedentary time decreased. No significant changes were observed in muscle mass or kinesiophobia. Conclusions: A structured, non-aerobic exercise program can effectively reduce body fat, alleviate fatigue, and improve pain perception in women with LC, supporting its role in rehabilitation. Multimodal strategies may be required to address cognitive symptoms and fear of movement.},
}

@article {pmid41464319,
year = {2025},
author = {Raycheva, R and Kostadinov, K and Rangelova, V and Kevorkyan, A},
title = {Economic Analyses of COVID-19 Interventions: A Narrative Review of Global Evidence.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {24},
pages = {},
doi = {10.3390/healthcare13243249},
pmid = {41464319},
issn = {2227-9032},
abstract = {Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic imposed an unprecedented global health and economic burden, prompting rapid implementation of diverse public health interventions. This review aimed to synthesize global evidence on the cost-effectiveness of key COVID-19 control strategies, including vaccination, testing, and social distancing and to identify methodological, contextual, and equity-related determinants of their economic value. Methods: A narrative literature review was conducted using peer-reviewed studies published between January 2020 and September 2025 and indexed in PubMed, Scopus, and Web of Science. Eligible studies included economic evaluations and modeling analyses addressing COVID-19 interventions in healthcare, community, or educational settings. Data on costs, outcomes, and methodological features were extracted and synthesized descriptively. Results: Across 74 included studies, vaccination-particularly with messenger RNA (mRNA) platforms-emerged as the most cost-effective intervention across all settings, often cost-saving among high-risk populations. Combined or layered strategies integrating vaccination, testing, and selective social distancing consistently outperformed single interventions in both health and economic outcomes. Early and targeted implementation yielded the highest cost-effectiveness by preventing exponential transmission and healthcare overload. However, heterogeneity in modeling assumptions, analytic perspectives, and outcome measures limited comparability. Few studies applied extended or distributional cost-effectiveness frameworks to address equity, while indirect and long-term effects such as productivity losses and "long COVID" were frequently omitted. Conclusions: COVID-19 interventions are most efficient when early, targeted, and adaptive to local epidemiologic conditions. Integrating equity, methodological consistency, and broader societal impacts into future evaluations will strengthen evidence-based, economically sustainable pandemic preparedness and response strategies.},
}

@article {pmid41463036,
year = {2025},
author = {Andriankaja, OM and Whiteheart, S and Mattos, MBA},
title = {Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13123023},
pmid = {41463036},
issn = {2227-9059},
abstract = {Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., "long-COVID," "post-acute sequelae of SARS-CoV-2 infection," "PASC," "post-COVID-19," "long-haul COVID") and oral/periodontal diseases (e.g., "periodontal disease," "periodontitis," "gingiva," "oral disease," "dental"), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein-Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships.},
}

@article {pmid41463013,
year = {2025},
author = {Petrov, S and Bozhkova, M and Ivanovska, M and Kalfova, T and Dudova, D and Nikolova, R and Vaseva, K and Todorova, Y and Aleksova, M and Nikolova, M and Taskov, H and Murdjeva, M and Maes, M},
title = {Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13123001},
pmid = {41463013},
issn = {2227-9059},
support = {BG-RRP-2.004-0007-C01//STRATEGIC RESEARCH AND INNOVATION PROGRAMME FOR THE DEVELOPMENT OF THE MEDICAL UNIVERSITY - PLOVDIV (SRIPD-MUP)/ ; },
abstract = {Background: Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and multisystemic symptoms, such as cognitive impairment, musculoskeletal pain, and post-exertional malaise. Recently, parallels have been drawn between ME/CFS and Long COVID, a post-viral syndrome following infection with SARS-CoV-2, which shares many clinical features with CFS. Both conditions involve chronic immune activation, raising questions about their immunopathological overlap. Objectives: This study aimed to compare immune biomarkers between patients with ME/CFS or Long COVID and healthy controls to explore shared immune dysfunction. Methods: We analyzed lymphocyte subsets, cytokine profiles, psychological status and their correlations in 190 participants, 65 with CFS, 54 with Long COVID, and 70 healthy controls. Results: When compared to healthy subjects, results in both conditions were marked by lower levels of lymphocytes (CFS-2.472 × 10[9]/L, p = 0.006, LC-2.051 × 10[9]/L, p = 0.009), CD8[+] T cells (CFS-0.394 × 10[9]/L, p = 0.001, LC-0.404 × 10[9]/L, p = 0.001), and NK cells (CFS-0.205 × 10[9]/L, p = 0.001, LC-0.180 × 10[9]/L, p = 0.001), and higher levels of proinflammatory cytokines such as IL-6 (CFS-3.35 pg/mL, p = 0.050 LC-4.04 pg/mL, p = 0.001), TNF (CFS-2.64 pg/mL, p = 0.023, LC-2.50 pg/mL, p = 0.025), IL-4 (CFS-3.72 pg/mL, p = 0.041, LC-3.45 pg/mL, p = 0.048), and IL-10 (CFS-2.29 pg/mL, p = 0.039, LC-2.25 pg/mL, p = 0.018). Conclusions: Notably, there were no significant differences between CFS and Long COVID patients in the tested biomarkers. These results demonstrate that ME/CFS and Long COVID display comparable immune and inflammatory profiles, with no significant biomarker differences observed between the two groups.},
}

@article {pmid41462874,
year = {2025},
author = {Halas, RG and Berceanu Vaduva, DM and Radulescu, M and Bredicean, AC and Mateescu, DM and Toma, AO and Cotet, IG and Guse, CE and Marginean, A and Margan, MM and Lazureanu, VE},
title = {Long COVID Prevalence and Risk Factors: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13122859},
pmid = {41462874},
issn = {2227-9059},
abstract = {Background: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects millions globally, with persistent symptoms impacting quality of life. This meta-analysis synthesizes prospective cohort studies to estimate the prevalence of Long COVID symptoms and identify risk factors. Methods: We systematically searched PubMed for prospective cohort studies (2020-2025) on Long COVID, focusing on prevalence and risk factors. Studies with ≥100 participants and follow-up ≥3 months were included. Data were extracted on symptom prevalence (e.g., fatigue, dyspnoea) and risk factors (e.g., sex, hospitalization). Random-effects models were used to pool prevalence and odds ratios (OR). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Results: Fourteen prospective studies (n = 168,679) were included. Pooled prevalence of Long COVID was 18.0% (95% CI: 12.5-23.5%, I[2] = 9.8%) among survivors followed for ≥6 months. Fatigue (41.0%, 95% CI: 33.2-49.4%) and dyspnoea (22.5%, 95% CI: 15.6-29.8%) were the most common symptoms. Female sex (OR = 1.52, 95% CI: 1.25-1.92) and prior hospitalization (OR = 2.35, 95% CI: 1.98-2.90) were significant risk factors. High heterogeneity (I[2] > 90%) was noted. Conclusions: Long COVID affects over one-fifth of SARS-CoV-2 survivors, with fatigue and dyspnoea persisting in many. Female sex and severe acute infection increase risk. Standardized definitions and longer follow-up are needed.},
}

@article {pmid41462744,
year = {2025},
author = {Fronticelli Baldelli, G and Buonsenso, D},
title = {Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.},
journal = {Children (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
doi = {10.3390/children12121603},
pmid = {41462744},
issn = {2227-9067},
abstract = {Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood-brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes.},
}

@article {pmid41462476,
year = {2025},
author = {Tamim El Jarkass, T and Nandakumar, S and Skidmore, B and Pinto, AD and Hosseini, B},
title = {Understanding how social determinants of health shape Long COVID outcomes: a rapid review of evidence.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {308},
pmid = {41462476},
issn = {0778-7367},
support = {Grant #FRN 183092 and PPE 190332/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Long COVID affects over 65 million people worldwide, yet the impact of social determinants of health (SDoH), such as socioeconomic status, race/ethnicity, education, occupation, and geography, remains poorly understood. To evaluate the association between SDoH and the risk and severity of Long COVID.

METHODS: A rapid review of observational studies was conducted using MEDLINE, Embase, and Web of Science (up to September 29, 2024). Studies reporting original data on SDoH and Long COVID outcomes were included. Data were extracted on study characteristics, population demographics, Long COVID definitions, and SDoH-related findings. Study quality was assessed using the Newcastle-Ottawa Scale.

RESULTS: Seventy-one studies (43 cohort, 28 cross-sectional) were included. Definitions of Long COVID varied. Commonly studied SDoH included age, sex, race/ethnicity, education, financial security, employment, and geography. Female sex and older age were consistently associated with increased risk and severity of Long COVID. Black and Hispanic individuals were more likely to experience Long COVID. Lower education and financial insecurity were also linked to greater prevalence and symptom burden. Frontline and essential workers were found to be at increased risk. Geographic disparities were evident but varied across rural and urban residence.

CONCLUSIONS: SDoH play a key role in shaping Long COVID outcomes. Addressing these disparities requires targeted public health efforts and standardized case definitions.},
}

@article {pmid41461919,
year = {2025},
author = {Kim, S and D'Anniballe, VM and Finlay, JB and Ko, T and Wang, M and Jang, DW and Abi-Hachem, R and Goldstein, BJ},
title = {Analysis of mucosal immune dysregulation and safety and tolerability of endoscopic topical steroid therapy for long-COVID hyposmia: randomized, double-blinded pilot study.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-025-01322-7},
pmid = {41461919},
issn = {2730-664X},
support = {DC020172//U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/ ; },
abstract = {BACKGROUND: Millions of people exhibit olfactory dysfunction years after acute SARS-CoV-2 infection. Evidence suggests unresolved olfactory epithelial inflammation may perturb function. Here, we report (1) data from human olfactory biopsies processed for T cell studies, and (2) outcomes from a pilot clinical trial evaluating endoscopic delivery of beclomethasone to the olfactory cleft for improving olfaction in long-COVID hyposmia.

METHODS: Biopsies from long-COVID hyposmia and control subjects underwent single-cell T-cell receptor (TCR) sequencing. In a separate outpatient cohort (Duke Rhinology Clinics), we conducted a randomized, double-blind, placebo-controlled pilot trial. Eligible adults (≥18 y) had ≥3 months long-COVID smell loss confirmed by Smell Identification Test (SIT). Participants were randomized 1:1 to endoscopic delivery of saline or beclomethasone via dissolvable sponge; repeated at 2 weeks. The primary outcome was SIT improvement ≥4 points at 1 month; secondary at 3 months. Study recruitment ran Sept 15, 2023-June 18, 2024.

RESULTS: Biopsies show no evidence of SARS-CoV-2 or EBV/HHV-6 reactivation and demonstrate clonally expanded, pro-inflammatory T-cell subsets. Fifteen subjects are randomized (beclomethasone n = 7, saline n = 8); 13 are analyzed (6 and 7). At 1 month, SIT improvement occurs in 66.7% (4/6) vs 28.6% (2/7) (risk difference 38.1%, 95% CI 2-97%; risk ratio 2.14, 95% CI 0.73-7.79; p = 0.28). At 3 months, rates are 66.7% vs 42.9% (RD 23.8%, 95% CI 17-80%; RR 1.74, 95% CI 0.52-6.5; p = 0.50). No adverse events are reported.

CONCLUSIONS: Human olfactory TCR-seq implicates local T-cell inflammation without local viral reservoirs. Directed, endoscopic topical steroid therapy is feasible and safe, with a non-significant trend toward improved olfaction, supporting larger trials.

FUNDING: NIH DC020172, American Academy of Otolaryngology-Head and Neck Surgery.},
}

@article {pmid41459516,
year = {2025},
author = {de Jesus Silva, J and Horta, LS and Viana, SM and Cazé, AB and Oliveira, IS and Pereira, MM and Antas Nascimento, N and Pereira, BJ and Bonyek-Silva, Í and Nunes de Oliveira Araújo, S and de Marinho, AIL and Rocha Cristal, J and Rao, V and Coelho, C and Cerqueira-Silva, T and Malmegrim, KCR and Camelier, A and Cardoso, CRB and Tavares, NM and Barral-Netto, M and Barral, A and Barbosa, C and Boaventura, VS},
title = {Autoantibodies in long COVID in a black/mixed population compared with recovered and pre-pandemic controls.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1684482},
pmid = {41459516},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/blood/ethnology ; *Autoantibodies/blood/immunology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Adult ; Aged ; Black People ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Long COVID (LC), a clinical condition marked by persistent and new symptoms after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects up to 10-20% of infected individuals. Although autoimmunity has been proposed as a key mechanism, the specific role of circulating autoantibodies in LC remains unclear. We characterized the autoantibody profiles in individuals with LC and assessed their association with persistent post-COVID symptoms, in comparison to recovered patients and pre-pandemic healthy controls (PPHC).

METHODS: We analyzed 17 autoantibodies in a cohort of 220 pre-pandemic controls and 291 COVID-19 patients, targeting self-antigens. Of those, 237 patients presented symptoms for a month or more after the onset of SARS-CoV-2 infection (long COVID patients), and 54 individuals recovered from the initial infection without chronic symptoms. Autoantibody frequencies and associations with clinical variables were assessed using logistic regression and subgroup analyses.

RESULTS: Autoantibody prevalence was higher in recovered individuals (37%) than in LC patients (24%) or PPHC (19%). While certain autoantibodies such as a-cardiolipin (a-CL) IgM, a-AML IgG, a-SSA IgG and a-SSB IgG were elevated in some COVID-19 patients, they were not significantly different in LC. The most frequently detected autoantibody was a-CL IgM, found across all groups and especially in individuals that fully recovered from COVID-19. However, a-CL did not differentiate individuals with long COVID or correlate with symptom persistence but was associated with the occurrence of dysphagia and anorexia as symptoms. No correlation was observed between autoantibody presence and disease severity.

DISCUSSION: These findings do not support a primary pathogenic role for the evaluated autoantibodies in LC and emphasize the need for longitudinal studies to explore their temporal dynamics and interaction with other immunological or clinical factors involved in post-COVID-19 conditions.},
}

Humans
*COVID-19/immunology/blood/ethnology
*Autoantibodies/blood/immunology
Male
Female
Middle Aged
*SARS-CoV-2/immunology
Adult
Aged
Black People
Post-Acute COVID-19 Syndrome

@article {pmid41457787,
year = {2025},
author = {Igarashi, Y and Tateishi, S and Sawajima, T and Harada, A and Matsuoka, J and Kawasumi, M and Mori, K},
title = {Occupational Physicians' Practices in Supporting Employees with Long COVID: A Mixed-Methods Study.},
journal = {Journal of occupational health},
volume = {},
number = {},
pages = {},
doi = {10.1093/joccuh/uiaf078},
pmid = {41457787},
issn = {1348-9585},
abstract = {OBJECTIVES: This study examined the support provided by occupational physicians (OPs) in Japan to employees with Long COVID, a condition that has significantly affected workforce health during the pandemic.

METHODS: An exploratory cross-sectional mixed-methods design was employed, consisting of qualitative interviews followed by a questionnaire survey targeting OPs certified by the Japan Society for Occupational Health. The interviews explored actual experiences of supporting workers with Long COVID, and the findings were used to develop the questionnaire. The survey and interview findings were integrated to describe overall occupational health practices.

RESULTS: Twenty OPs reported 30 cases of employees with Long COVID in the interviews. Based on these findings, a questionnaire survey was conducted, yielding 182 valid responses. The integrated results showed that OPs most frequently reported Main OH Responses such as active listening, return-to-work assistance, and lifestyle guidance. Measures such as explaining workers' compensation applications and preparing lists of outpatient clinics were less frequently reported. For Advice for Employers, limitation of overtime, reduction of workload, and telework were commonly reported, whereas demotion and reassignment were rarely reported.

CONCLUSIONS: This study clarified how OPs in Japan supported workers with Long COVID through diverse, context-dependent practices. The identified Main OH Responses and Advice for Employers provide a framework for understanding current practices. Developing practical case examples, structured assessment tools, and workplace guidelines, together with further research grounded in real-world practice, will enhance OPs' ability to provide appropriate support and strengthen preparedness for future health crises.},
}

@article {pmid41457697,
year = {2025},
author = {Lin, LY and Chen, CJ and Chen, MH and Chen, CW and Chen, PC},
title = {The association between COVID-19 and incident gestational diabetes (GDM): A population-based case-control study of the National Health Insurance Research Database in Taiwan.},
journal = {Journal of diabetes investigation},
volume = {},
number = {},
pages = {},
doi = {10.1111/jdi.70228},
pmid = {41457697},
issn = {2040-1124},
support = {NTU-NFG-113L7463//National Taiwan University/ ; NTU-NFG-114L7406//National Taiwan University/ ; NHRI-EM-113-GP-03//National Health Research Institutes/ ; NHRI-EM-114-GP-03//National Health Research Institutes/ ; NSTC 113-2314-B-002-316-//National Science and Technology Council/ ; NSTC 114-2314-B-002-110-//National Science and Technology Council/ ; },
abstract = {BACKGROUND: Reports suggested that diabetes could be a complication arising from COVID-19; however, the relationship between COVID-19 and the development of gestational diabetes mellitus (GDM) remains unclear.

OBJECTIVES: This study aimed to investigate the association between COVID-19 infections and the risk of incident GDM in pregnant women.

METHODS: We analyzed data from Taiwan's National Health Insurance Research Database (NHIRD), which is linked to the Birth Reporting Database and the COVID-19 testing database between 2020 and 2022. A case-control study was conducted, matching pregnant women by age and region. We employed multivariable logistic regression, adjusting for matching factors and potential confounders. The findings were further validated through a sensitivity analysis using a cohort design with landmark analysis.

RESULTS: The study included 134,375 pregnant women, comprising 26,875 GDM cases and 107,500 matched controls. After adjusting for covariates, we found no evidence supporting an association between prior COVID-19 infection and incident GDM (adjusted odds ratio [aOR] = 0.95, 95% confidence interval [CI] = 0.89-1.01). Notably, some evidence showed that receiving at least one COVID-19 vaccination was associated with a decreased risk of GDM (aOR = 0.90, 95% CI = 0.87-0.93). These results remained consistent in the sensitivity analysis.

CONCLUSION: Despite COVID-19 now being endemic with less virulent variants, ongoing vigilance regarding potential pregnancy-related impacts of SARS-CoV-2 is essential. It is also critical to promote vaccination among women of childbearing age, and further research is necessary to explore COVID-19-related complications during pregnancy.},
}

@article {pmid41457003,
year = {2025},
author = {Plaut, S},
title = {Correspondence on 'Rheumatology and Long COVID: lessons from the study of fibromyalgia?' by Clauw and Calabrese.},
journal = {Annals of the rheumatic diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ard.2025.12.001},
pmid = {41457003},
issn = {1468-2060},
}

@article {pmid41455934,
year = {2025},
author = {Sisti, JS and Packard, SE and Metzler, J},
title = {Long COVID symptoms and loneliness: findings from the World Trade Center Health Registry.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-025-26006-8},
pmid = {41455934},
issn = {1471-2458},
support = {U50OH009739/OH/NIOSH CDC HHS/United States ; U50OH009739/OH/NIOSH CDC HHS/United States ; NE11OE000057/CC/CDC HHS/United States ; },
abstract = {BACKGROUND: Symptoms of long COVID can profoundly impact affected individuals' functioning, including their ability to participate in social activities. While individuals experiencing long COVID symptoms frequently report loneliness, few studies to date have investigated whether loneliness is more common among those with symptoms compared to those without. We examined associations between long COVID symptoms and loneliness among World Trade Center Health Registry (WTCHR) enrollees.

METHODS: Among WTCHR enrollees who reported an acute COVID-19 infection in 2022-23 on a self-administered survey, we used modified Poisson regression to estimate multivariable-adjusted prevalence ratios (PR) and 95% confidence intervals (95% CI) for associations of self-reported long COVID symptoms (any vs. none, selected from a predefined symptom list) with loneliness. Overall loneliness was assessed with the 6-item de Jong Gierveld loneliness scale (range: 0-6); social and emotional loneliness were assessed with their respective subscales (range: 0-3). We also assessed whether level of social support prior to COVID-19 infection modified associations of long COVID symptoms with loneliness.

RESULTS: Analyses included 5,692 enrollees (mean age: 62 years); prevalence of loneliness was 61%. In fully adjusted models, enrollees who reported any long COVID symptoms had higher prevalence of loneliness compared to those without symptoms (PR = 1.19, 95% CI:1.13, 1.25). Associations were somewhat stronger for emotional loneliness than for social loneliness (PR = 1.22, 95% CI:1.15, 1.29 and PR = 1.12, 95% CI:1.07, 1.18, respectively). Effect modification by social support was not observed on either the additive or multiplicative scale.

CONCLUSION: Long COVID symptoms were associated with prevalence of loneliness in a sample of primarily older adults. As loneliness itself is associated with subsequent adverse health outcomes, addressing loneliness among people living with long COVID may help prevent further reductions in quality of life.},
}

@article {pmid41447955,
year = {2025},
author = {Talamini, L and Verdot, C and Shoenfeld, Y and Muller, S},
title = {Pathophysiological effects of long COVID-19 (auto)antibodies on fertility.},
journal = {Journal of autoimmunity},
volume = {158},
number = {},
pages = {103518},
doi = {10.1016/j.jaut.2025.103518},
pmid = {41447955},
issn = {1095-9157},
abstract = {Molecular mimicry between foreign and self-antigens has long been recognized to initiate/exacerbate autoimmunity. Shared amino acid sequences have been found between SARS-CoV-2 Spike glycoprotein and human self-proteins, raising concerns about potential damages. We previously identified sequences with ≥5 identical residues shared by the SARS-CoV-2 Spike and spermatogenesis-associated proteins. One of these peptides was especially recognized by antibodies from infected, but not vaccinated individuals. Here, their pathogenic effects were explored in vivo. Injection of peptide antibodies into healthy male mice impaired fertility or delayed delivery time in fertile females, suggesting that cross-reactivity via molecular mimicry might affect the human reproductive system.},
}

@article {pmid41445780,
year = {2025},
author = {N, SR and Jin, GW and Choy, JH},
title = {Translational potential of safe-by-design nanoengineered niclosamide in viral and cancer therapy.},
journal = {Materials today. Bio},
volume = {35},
number = {},
pages = {102610},
pmid = {41445780},
issn = {2590-0064},
abstract = {This study presents a comprehensive evaluation of the long-term biocompatibility of CP-COV03 (NIC-MgO-HPMC), a nanohybrid formulation of niclosamide designed to overcome its limitations in solubility, stability, and bioavailability. Developed under a safe-by-design framework, NIC-MgO-HPMC integrates magnesium oxide (MgO) nanoparticles with hydroxypropyl methylcellulose (HPMC) to enhance pharmacological performance while ensuring safety for chronic use. Over a 13-week in vivo exposure period, the toxicological profile was systematically assessed, focusing on hepatic, renal, and hematologic systems. Clinical observations, serum biochemistry, and hematology revealed no abnormalities at clinically relevant dosages. Histopathological examination of major organs confirmed the absence of tissue damage or structural alterations, underscoring the nanohybrid's long-term tolerability. These findings establish the first foundational safety benchmark for chronic use of nanoengineered niclosamide hybrids. The absence of systemic toxicities validates CP-COV03 as a scalable and biocompatible therapeutic platform suitable for extended dosing regimens. By combining durable safety with enhanced drug performance, CP-COV03 offers strong translational potential for persistent viral infections, including long COVID, future pandemic threats, and oncology applications.},
}

@article {pmid41445680,
year = {2025},
author = {Tura, NC and da Silva Pereira, F and Fogaça, B and Pang, AS and do Amaral, LA and Barbosa, RI},
title = {Efficacy of Synchronous vs. Asynchronous Telerehabilitation for Musculoskeletal Symptoms in Post-Covid-19 Syndrome: A Randomized Clinical Trial.},
journal = {International journal of telerehabilitation},
volume = {17},
number = {2},
pages = {6716},
pmid = {41445680},
issn = {1945-2020},
abstract = {OBJECTIVE: Compare the effects of physiotherapist-supervised synchronous telerehabilitation (TR) with unsupervised asynchronous TR in adults diagnosed with post-COVID syndrome (PCS).

METHODS: In this single-blind randomized controlled trial conducted with 31 participants with PCS were randomized into a synchronous telerehabilitation (STR) group, which underwent two-hour sessions per week for eight weeks, and an asynchronous telerehabilitation (ATR) group, which performed unsupervised exercises. Lower limb functional strength (Five Times Sit-to-Stand Functional Test) as the primary outcome, and the dyspnea (Modified Medical Research Council), fatigue (Fatigue Assessment Scale), stress, anxiety, depression (Depression, Anxiety, and Stress Scale-21), and quality of life (World Health Organization Quality of Life-BREF Questionnaire) were assessed remotely at the baseline, after 8 weeks of intervention, and at a 20-week follow-up. Data were analyzed using a mixed-model analysis of variance.

INTERVENTION: Participants were randomized into a synchronous telerehabilitation (TRS) group, which performed two-hour sessions per week for eight weeks, and an asynchronous telerehabilitation (TRA) group, which performed the same exercise protocol but without the supervision of a physiotherapist. Instructional videos were made available via social media (WhatsApp and YouTube). Participants were also instructed to perform the protocol twice a week for eight weeks.

RESULTS: A statistically significant difference was only observed in lower limb functionality between both groups (p = 0.02). The STR group demonstrated significant improvements in lower limb functional strength (p = 0.03), dyspnea (p = 0.02), fatigue (p = 0.00), stress (p = 0.03), and quality of life (p = 0.00), without any adverse events. Conversely, the ATR group experienced significant improvements in fatigue (p = 0.00) and anxiety (p = 0.02).

CONCLUSION: The present findings show that both modalities demonstrated positive effects over an 8-week TR program in adults with PCS. However, the synchronous approach achieved greater improvements in lower limb functionality, dyspnea, fatigue, stress, and quality of life. Our findings revealed that asynchronous model was associated with higher dropout rates and suggest synchronous TR may offer advantages regarding treatment adherence.},
}

@article {pmid41444262,
year = {2025},
author = {Wilson, JE and Gurdasani, D and Helbok, R and Ozturk, S and Fraser, DD and Filipović, SR and Peluso, MJ and Iwasaki, A and Yasuda, CL and Bocci, T and Priori, A and Altmann, D and Alwan, NA and Wesley Ely, E},
title = {COVID-19-associated neurological and psychological manifestations.},
journal = {Nature reviews. Disease primers},
volume = {11},
number = {1},
pages = {91},
pmid = {41444262},
issn = {2056-676X},
mesh = {Humans ; *COVID-19/complications/psychology/physiopathology/epidemiology ; *Nervous System Diseases/etiology/virology ; *Mental Disorders/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anxiety/etiology ; Depression/etiology ; },
abstract = {Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5-20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must be tailored based on a patient's presenting symptoms.},
}

Humans
*COVID-19/complications/psychology/physiopathology/epidemiology
*Nervous System Diseases/etiology/virology
*Mental Disorders/etiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Anxiety/etiology
Depression/etiology

@article {pmid41442105,
year = {2025},
author = {Riste, L and Perrin, R and Mulholland, T and Hann, M and McDonald, O and Heald, A},
title = {Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT).},
journal = {Infectious diseases and therapy},
volume = {},
number = {},
pages = {},
pmid = {41442105},
issn = {2193-8229},
support = {FORME 5//Stiftelsen för Synskadade i f.d. Malmöhus län/ ; },
abstract = {INTRODUCTION: Long COVID-related fatigue affects a large number of people across the world, with increasing numbers of people experiencing long-term disability as a consequence. We tested the feasibility of a self-help version of a manual osteopathic approach initially developed for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to treat people with long COVID-related fatigue.

METHODS: Our feasibility study assessed recruitment into a 1:1 randomized controlled trial (RCT) to receive (i) self-help intervention (self-massage, mobility, flexibility, and breathing exercises, and alternating cold and warm packs to the top of the spine) or (ii) wait-list control group. Follow-up was assessed by online surveys at 3 and 6 months (indicating retention). Verbal feedback was obtained from participants.

RESULTS: Of the 138 eligible survey participants, 126 (90.6%) agreed to participate in two RCTs, achieving the required sample size of 100. Follow-up rates of 79.3% and 59.4% were achieved at 3 and 6 months, respectively. Improvements in Chalder Fatigue Questionnaire (CFQ) scores were observed in both groups between 0 and 3 months (- 4.6 and - 2.9, respectively), to a greater degree in the intervention group (p = 0.01). Feedback showed a cohort keen to engage with the intervention, although some found the intervention onerous at times.

CONCLUSIONS: We have reported the results of a feasibility study examining a potentially beneficial intervention for people with long COVID. There were indications of benefit in a patient group with often intractable symptoms. Based on this feasibility study, we believe that the low-cost self-help intervention in isolation could help support fatigue reduction in some people. This has implications for the treatment of both long COVID and ME/CFS.

TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 99840264.},
}

@article {pmid41441042,
year = {2025},
author = {Cai, E and Kouznetsova, VL and Tsigelny, IF},
title = {Metabolomics-Based Machine Learning Diagnostics of Post-Acute Sequelae of SARS-CoV-2 Infection.},
journal = {Metabolites},
volume = {15},
number = {12},
pages = {},
pmid = {41441042},
issn = {2218-1989},
abstract = {Background: COVID-19 has taken millions of lives and continues to affect people worldwide. Post-Acute Sequelae of SARS-CoV-2 Infection (also known as Post-Acute Sequelae of COVID-19 (PASC) or more commonly, Long COVID) occurs in the aftermath of COVID-19 and is poorly understood despite its widespread effects. Methods: We created a machine-learning model that distinguishes PASC from PASC-similar diseases. The model was trained to recognize PASC-dysregulated metabolites (p ≤ 0.05) using molecular descriptors. Results: Our multi-layer perceptron model accurately recognizes PASC-dysregulated metabolites in the independent testing set, with an AUC-ROC of 0.8991, and differentiates PASC from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, postural orthostatic tachycardia syndrome (POTS), and irritable bowel syndrome (IBS). However, it was unable to differentiate fibromyalgia (FM) from PASC. Conclusions: By creating and testing models pairwise on each of these diseases, we elucidated the unique strength of the similarity between FM and PASC relative to other PASC-similar diseases. Our approach is unique to PASC diagnosis, and our use of molecular descriptors enables our model to work with any metabolite where molecular descriptors can be identified, as these descriptors can be generated and compared for any metabolite. Our study presents a novel approach to PASC diagnosis that partially circumvents the lengthy process of exclusion, potentially facilitating faster interventions and improved patient outcomes.},
}

@article {pmid41440526,
year = {2025},
author = {László, SA and Ianoși, ES and Văsieșiu, AM and Szathmáry, M and Ianoși, MB and Rachiș, DL and Nistor, G and Jimborean, G},
title = {COVID-19 and Lung Cancer Interactions: A Literature Review.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
pmid = {41440526},
issn = {2076-3271},
mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Lung Neoplasms/epidemiology/diagnosis/virology ; SARS-CoV-2 ; Incidence ; Pandemics ; },
abstract = {This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- and mid-stage diagnostic process, which causes a shift to late-stage lung cancer discovery with no impact on its actual prevalence, an alternative hypothesis based on the intersection of viral and cancer biology could have a real effect on lung carcinogenesis as an independent phenomenon. By weaving together population-level trends, mechanistic insights, and translational oncology, we discuss whether the pandemic-associated decline in lung cancer diagnoses reflects primarily a temporary diagnostic artifact or whether it also reveals biologically relevant intersections between SARS-CoV-2 and pulmonary oncogenesis. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted profound and multifaceted effects on global healthcare systems, altering patterns of disease detection, management, and outcomes across nearly all medical disciplines. These disruptions generated what has been termed a "diagnostic deficit", producing a backlog of undetected cancers that have only partially been recovered in subsequent years. This phenomenon, sometimes described as a "COVID-19 debt" in oncology, is thought to contribute to excess late-stage diagnoses and potentially worse medium-term survival outcomes. Beyond the disruption of medical systems, the pandemic also raised a more speculative but biologically intriguing question: could SARS-CoV-2 infection itself, through direct or indirect mechanisms, influence lung cancer biology? Our review aims to critically synthesize the evidence across seven domains to address this dual hypothesis. (1) We examine the observed effects of the pandemic on cancer incidence, highlighting global registry and health-system data; (2) we review SARS-CoV-2 infection biology, including viral entry, replication, protein functions, and treatment implications; (3) we summarize the pathogenesis of lung cancer; (4) we explore the role of immune checkpoints in tumor immune evasion, followed by (5) analyses of immune dysregulation in acute infection and (6) in long COVID; and (7) finally, we evaluate proposed oncogenic mechanisms of SARS-CoV-2, integrating molecular virology with cancer immunology. We conclude that the "diagnostic deficit" phenomenon was a reality during and immediately post-pandemic. However, a definitive answer to the questions related to the impact of the infection as an independent phenomenon would require advanced research information covering the biology of the viral infection and lung cancer oncogenesis: processes that are not currently implemented in routine clinical laboratory investigations.},
}

Humans
*COVID-19/epidemiology/complications/virology
*Lung Neoplasms/epidemiology/diagnosis/virology
SARS-CoV-2
Incidence
Pandemics

@article {pmid41439932,
year = {2025},
author = {Zuñiga-Jimenez, CT and Rojas-Esguerra, DF and Muñoz-Martinez, AP and Mendoza-Guzman, DC and Daza-Arana, JE},
title = {Musculoskeletal Sequelae of Post-COVID-19 Syndrome: A Systematic Review.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {41439932},
issn = {2079-9721},
abstract = {Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient's quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case-control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients' daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients.},
}

@article {pmid41439849,
year = {2025},
author = {Bowers, K and Benoit, S and Rose, J and Beck, AF and Folger, AT and Calhoun, TN and Day, ME and Lovell, A and Amin, M},
title = {High Household Transmission Among Asymptomatic Contacts Across Pandemic Waves in Cincinnati, Ohio.},
journal = {Epidemiologia (Basel, Switzerland)},
volume = {6},
number = {4},
pages = {},
pmid = {41439849},
issn = {2673-3986},
support = {UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1TR001425-05A1/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND/OBJECTIVES: COVID-19 and long COVID remain prevalent, with household transmission being an important mode of spread. To quantify household transmission of subclinical SARS-COV-2 infection and identify sociodemographic risk factors that may explain disparities in transmission, we conducted a case-ascertained antibody surveillance study of households in Cincinnati, Ohio.

METHODS: A partnership was formed between the Cincinnati Health Department and Cincinnati Children's Hospital Medical Center. The Health Department identified cases of COVID-19. Infected individuals, along with their household contacts (n = 245), completed multiple questionnaires about symptoms, demographics, psychosocial (Adverse Childhood Experiences Scale and Everyday Discrimination Scale) and social risk factors, and conditions before and during the pandemic. In addition, they completed a non-fasting blood draw for IgG, IgM, IgA, and nucleocapsid protein serology testing.

RESULTS: Household contacts experienced few symptoms of COVID-19. However, according to the presence of the nucleocapsid protein, nearly 50% contracted the SARS-CoV-2 virus. This rate was similar by vaccination status but it was higher for household contacts who experienced high levels of early life adversity compared with those with lower levels.

CONCLUSIONS: Our results confirm the high transmission of subclinical disease among household contacts, which may vary due to psychosocial factors. This reinforces the importance of isolating cases to prevent transmission, regardless of vaccination status.},
}

@article {pmid41438970,
year = {2025},
author = {Oostwouder, CJ and Vos, K and Lutke Schipholt, IJ and Merkus, MR and Telders, T and van Deursen, DFA and de Smit, MB and van Eijk, MD and Bontkes, HJ and Bouwman, FH and Wüst, RCI and de Jong, L and van Hulst, M and Twisk, JWR and van Kalken, CK and Scholten-Peeters, GGM},
title = {Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study.},
journal = {EClinicalMedicine},
volume = {90},
number = {},
pages = {103681},
pmid = {41438970},
issn = {2589-5370},
abstract = {BACKGROUND: Post-COVID involves persistent, multisystem symptoms which are associated with inflammation, immune dysregulation, and autonomic dysfunction. The effects of currently applied treatments for post-COVID are limited. This study assessed the effectiveness of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of post-COVID.

METHODS: This interrupted time series study was conducted at a Dutch outpatient clinic between August 2024 and April 2025. Adults with physician-diagnosed post-COVID (n = 103) underwent a 4-week pre-treatment observation followed by 24-36 weeks of home-based subcutaneous lidocaine 5% with HP-β-CD, administered using a 3-phase protocol: 500 mg every other day (weeks 1-7), 500 mg daily (weeks 7-14), and up to 1000 mg/day (after week 14, in non-responders). The primary outcome was health-related quality of life (Short Form-12 (SF-12), physical and mental component summary scores). Secondary outcomes included symptom burden (daily app-based questionnaire) and adverse events.

FINDINGS: Among 103 participants (mean [SD] age 48·1 [13·0] years; 67% women; median [IQR] symptom duration 31·5 [24·3-43·3] months), 76% completed 24 weeks and 71% completed 36 weeks of treatment. At week 24, the physical and mental component scores increased by 2·20 and 5·16 points, respectively; at week 36, by 4·13 and 7·00 points (all p < 0·0001). Twenty-seven of 30 symptoms improved significantly at week 24 of treatment compared to pre-treatment. Mild adverse events occurred in 89% of participants, mostly injection-site reactions; no serious adverse events were reported.

INTERPRETATION: Subcutaneous lidocaine-HP-β-CD was associated with significantly improved quality of life and symptom burden in patients with post-COVID. This home-administered intervention offers a scalable and potentially disease-modifying approach for a disabling condition with no approved treatment to date.

FUNDING: Excellent Care Clinics funded the treatment provided in this study.},
}

@article {pmid41438927,
year = {2025},
author = {Cheng, AL and Barker, R and von Nordheim, D and McQueen, A},
title = {Long COVID: What is it? Who has it? What Are Treatment Resources in Missouri?.},
journal = {Missouri medicine},
volume = {122},
number = {6},
pages = {488-494},
pmid = {41438927},
issn = {0026-6620},
mesh = {Humans ; Missouri/epidemiology ; *COVID-19/epidemiology/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {As we pass the five-year mark since the COVID-19 pandemic hit, the prevalence of persistent (and often disabling) symptoms from the SARS-CoV-2 virus is estimated to be on par with the prevalence of heart disease. Yet, these Long COVID symptoms can masquerade as other conditions and/or normal aging, so it is believed that Long COVID is under-diagnosed and, as a result, under-treated. Although there is not yet a true cure for Long COVID, many patients benefit substantially from rehabilitation strategies, medications, and social support resources that are available in Missouri. The purpose of this article is to review the definition and epidemiology of Long COVID, provide practical guidance for Long COVID assessment and management especially in the primary care setting, and increase awareness of regional resources for people in Missouri who are living with Long COVID and for the clinicians who are caring for them.},
}

Humans
Missouri/epidemiology
*COVID-19/epidemiology/complications/therapy
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid41436401,
year = {2025},
author = {Delano, P and Serra-Sutton, V and Rodriguez-Arjona, D and Benavides, FG and Vives, A and Utzet, M},
title = {Long COVID and its impact on healthcare worker's job performance. A qualitative study in Spain.},
journal = {Journal of occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/JOM.0000000000003650},
pmid = {41436401},
issn = {1536-5948},
abstract = {OBJECTIVE: To explore the experiences of healthcare workers (HCWs) in Spain with long COVID and its impact on their job performance, from the perspectives of affected HCWs, healthcare providers, and key stakeholders.

METHODS: A phenomenological, constructivist approach was used. Seven online focus groups and four interviews were conducted from April to June 2024. Transcripts were thematically analysed using Atlas.ti using a predefined guideline.

RESULTS: Long COVID significantly impaired work ability due to physical and cognitive limitations. Sick leave followed long-term or intermittent patterns, though many HCWs hesitated to take leave. Return-to-work experiences were shaped by workplace adaptations, institutional support, and persistent symptoms. Improvement proposals include formal recognition and holistic workplace support as they are essential to reduce its occupational burden.

CONCLUSIONS: Long COVID significantly impacts affected HCWs job performance, highlighting a need for recognition, support and workplace adaptation.},
}

@article {pmid41432873,
year = {2025},
author = {Michael, HU and Aste, FG and Brouillette, MJ and Fellows, LK and Mayo, NE},
title = {How do fatigue, cognitive dysfunction, activity and role functioning, and mental health inter-relate in adults with post-COVID-19 syndrome? A structural equation model analysis.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {1},
pages = {3},
pmid = {41432873},
issn = {1573-2649},
mesh = {Humans ; Male ; Female ; *COVID-19/psychology/complications ; *Fatigue/psychology/etiology ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Cognitive Dysfunction/psychology/etiology ; *Mental Health ; Quebec/epidemiology ; SARS-CoV-2 ; Latent Class Analysis ; Aged ; *Activities of Daily Living/psychology ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE: Post-COVID-19 Syndrome (PCS) is associated with persistent fatigue and cognitive symptoms that may disrupt daily functioning and mental health. This study examined interrelationships among fatigue, cognitive function, activity and role functioning, and mental health in individuals with PCS.

METHODS: We analyzed cross-sectional data from 535 adults in the Quebec Action for Post-COVID (QAPC) cohort who self-identified as experiencing PCS symptoms. Structural Equation Modelling was used to estimate associations among fatigue, self-reported cognitive concerns, cognitive performance, and two latent constructs: activity and role functioning and mental health. Models were adjusted for age, sex, education, race, alcohol use, prior mental health history, and vaccination status.

RESULTS: Fatigue showed association with mental health (standardized regression coefficient, β_std = 0.44, p < 0.001), primarily through a direct path (β_std = 0.42) and a smaller indirect path via self-reported cognitive concerns (β_std = 0.10). Fatigue was also associated with reduced activity and role functioning (β_std = - 0.79), which did not mediate its link to mental health. Self-reported cognitive concerns were independently associated with poorer mental health (β_std = 0.19). Cognitive performance was positively associated with activity and role functioning (β_std = 0.11) but not with mental health. Covariates, including older age, Caucasian ethnicity, and vaccination, were linked to more favourable outcomes.

CONCLUSION: Fatigue and self-reported cognitive concerns were associated with mental health symptoms in PCS. These findings highlight the value of symptom cluster-based screening to inform referral pathways for cognitive, psychological, and functional support. Longitudinal research is needed to clarify temporal ordering.},
}

Humans
Male
Female
*COVID-19/psychology/complications
*Fatigue/psychology/etiology
Cross-Sectional Studies
Middle Aged
Adult
*Cognitive Dysfunction/psychology/etiology
*Mental Health
Quebec/epidemiology
SARS-CoV-2
Latent Class Analysis
Aged
*Activities of Daily Living/psychology
Post-Acute COVID-19 Syndrome

@article {pmid41431672,
year = {2025},
author = {Jang, J and Ju, H and Song, GH and Kim, M and Hwang, G and Park, J and Kim, SS},
title = {Korea Disease Control and Prevention Agency Infectious Disease Big Data: Opening, Integration, Outcomes, and Future Directions.},
journal = {Jugan geon-gang gwa jilbyeong},
volume = {18},
number = {49},
pages = {2037-2057},
pmid = {41431672},
issn = {2586-0860},
abstract = {OBJECTIVES: The recurring emergence of novel infectious diseases highlights the need for evidence-based policies grounded in real-world data. This study aimed to examine the strategies of the Korea Disease Control and Prevention Agency (KDCA) in establishing and opening up infectious disease big data and to analyze their policy implications.

METHODS: The KDCA developed the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service (K-COV-N) cohort by linking coronavirus disease 2019 (COVID-19) cases and vaccination records with the National Health Insurance Service data, providing access to researchers since 2022. In 2024, the Infectious Disease Big Data Platform was launched, releasing standardized and anonymized datasets for 64 notifiable diseases. In addition, the Infectious Disease Statistics Dashboard and open application programming interface via the Public Data Portal have enhanced accessibility for both researchers and the public.

RESULTS: These open data resources have enabled diverse studies, including vaccine effectiveness evaluation, risk analysis for vulnerable populations, post-acute sequelae of COVID-19 (long COVID) research, and assessment of healthcare system impacts. Furthermore, they bridged research and policy practices, supporting the transition toward preventive health policies and strengthening infectious disease response capacity.

CONCLUSIONS: The infectious disease big data initiatives of the KDCA have functioned as a core infrastructure for evidence-informed policy-making. Integrating additional domains, such as chronic diseases, national health surveys, injuries, and genomics, and applying artificial intelligence-enabled deep analytics and prediction will provide a stronger foundation for protecting population health and enhancing national health security.},
}

@article {pmid41428252,
year = {2025},
author = {Yet, M and Teo, HS and Kwa, H and Yeo, J and Wang, SSY},
title = {Long COVID: a review of mechanisms and treatment modalities.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41428252},
issn = {1568-5608},
abstract = {Long COVID is defined by the World Health Organisation (WHO) as a condition arising within 3 months of an acute COVID infection with symptoms lasting for a minimum of 2 weeks. However, this syndrome is poorly understood and has been recorded to include many systemic manifestations, including neurological, respiratory, cardiovascular, gastrointestinal, dermatological, psychosocial, and metabolic systems. Constitutional symptoms also include fatigue, insomnia, body weight changes, poor attention span, hair loss, sexual dysfunction, myalgia, and joint pain, with fatigue being the most common. Given the various proposed mechanisms published in the literature, the postulated mechanisms and pathways are discussed in this paper to contribute to the understanding of defining this syndrome. In this review article, the authors first explored how endothelial damage from COVID infection can lead to a hypercoagulable state. In addition, the effects of an insufficient initial immune response can lead to viral persistence alongside a potentially prolonged hyperactive immune response that includes a cytokine storm and mast cell activation syndrome. Furthermore, the viral persistence can be exacerbated by antibody-dependent enhancement or complicated by molecular mimicry. Current pharmacological therapies are explored and evaluated to investigate their efficacy in addressing this complex and chronic presentation. This review article has been written after an extensive literature review to increase the understanding and awareness regarding Long COVID, as a sincere effort to direct further research for an effective diagnosis and management.},
}

@article {pmid41426345,
year = {2025},
author = {Blitshteyn, S},
title = {Long COVID: a long road ahead.},
journal = {Oxford open immunology},
volume = {6},
number = {1},
pages = {iqaf010},
pmid = {41426345},
issn = {2633-6960},
abstract = {The SARS-CoV-2 pandemic caused an estimated 400 million people worldwide to experience Long COVID and post-COVID complications leading to significant chronic illness and disability with its devastating physical, societal and economic consequences. Since post-acute infectious syndromes have not been given adequate consideration prior to the pandemic, many millions of people with Long COVID worldwide have been left disabled as currently available therapies are largely symptomatic and only partially effective. A case of a previously healthy woman with Long COVID and post-COVID autonomic dysfunction and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is presented here from the perspective of a physician-patient relationship and a broader context of medical care and public health. Immunologic and autonomic mechanistic factors and therapies as these relate to Long COVID are highlighted. Complexities and issues pertaining to patient care, public health and education of neurologists and other specialists regarding Long COVID, dysautonomia and ME/CFS diagnosis and treatment are discussed, in conjunction with the need to develop and diversify effective therapies for people living with these highly disabling conditions.},
}

@article {pmid41425584,
year = {2025},
author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A},
title = {The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1710571},
pmid = {41425584},
issn = {1664-3224},
mesh = {Humans ; *Autoimmune Diseases/immunology/genetics/etiology ; *Haplotypes ; Genetic Predisposition to Disease ; Autoimmunity ; *Histocompatibility Antigens Class II/genetics/immunology ; Animals ; },
abstract = {The prevalence of autoimmune diseases in contemporary human populations poses a challenge for both medicine and evolutionary biology. This review explores how the ancestral human leukocyte antigen class II (HLA-II) haplotypes DR2-DQ6, DR4-DQ8 and DR3-DQ2 could play a central role in susceptibility to these diseases. We propose that these haplotypes, selected in historical contexts of high infectious pressure, may have been maintained because of their ability to elicit strong T-cell responses against pathogens; however, that antigenic promiscuity may be associated with an increased tendency toward immune hyperreactivity in modern environments. This hyperreactivity, involving proinflammatory cytokines including interferon-gamma (IFN-γ), could contribute to the breakdown of tolerance and the emergence of autoimmunity and related clinical phenomena (e.g., Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome and post-vaccination syndromes), although the evidence for the latter remains limited. Finally, we discuss how chronic infections, immunotherapies, vaccination, obesity and chronic physical stressors may exacerbate this susceptibility and consider the therapeutic implications of integrating HLA-II profiling into clinical practice.},
}

Humans
*Autoimmune Diseases/immunology/genetics/etiology
*Haplotypes
Genetic Predisposition to Disease
Autoimmunity
*Histocompatibility Antigens Class II/genetics/immunology
Animals

@article {pmid41424383,
year = {2025},
author = {Ashok, D and Liu, T and Nakanishi-Koakutsu, M and Criscione, J and Prakash, M and Tensfeldt, A and Kim, B and Ho, B and Chow, J and Craney, M and Ranek, MJ and Lin, BL and Papanicolaou, K and Sidor, A and Foster, DB and Cho, HC and Pekosz, A and Villano, J and Kim, DH and O'Rourke, B},
title = {Innate immune activation and mitochondrial ROS induce acute and persistent cardiac conduction system dysfunction after COVID-19.},
journal = {JCI insight},
volume = {10},
number = {24},
pages = {},
doi = {10.1172/jci.insight.193164},
pmid = {41424383},
issn = {2379-3708},
mesh = {Animals ; *COVID-19/complications/immunology/physiopathology ; *Immunity, Innate ; *Arrhythmias, Cardiac/immunology/physiopathology/etiology/virology ; SARS-CoV-2 ; *Reactive Oxygen Species/metabolism ; Humans ; *Heart Conduction System/physiopathology/immunology ; Cricetinae ; Disease Models, Animal ; Male ; Myocytes, Cardiac/metabolism/immunology ; *Mitochondria/metabolism ; Cytokines/metabolism ; Electrocardiography ; Poly I-C ; },
abstract = {Cardiac arrhythmias increase during acute SARS-CoV-2 infection and in long COVID syndrome, by unknown mechanisms. This study explored the acute and long-term effects of COVID-19 on cardiac electrophysiology and the cardiac conduction system (CCS) in a hamster model. Electrocardiograms and subpleural pressures were recorded by telemetry for 4 weeks after SARS-CoV-2 infection, and interferon-stimulated gene expression and macrophage infiltration of the CCS were assessed at 4 days and 4 weeks postinfection. COVID-19 induced pronounced tachypnea and cardiac arrhythmias, including bradycardia and persistent atrioventricular block, though no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped, indicating persistent CCS injury. COVID-19 induced cardiac cytokine expression, connexin mislocalization, and CCS macrophage remodeling. Interestingly, sterile innate immune activation by direct cardiac injection of polyinosinic:polycytidylic acid (PIC) induced arrhythmias similar to those of COVID-19. PIC strongly induced cytokine secretion and interferon signaling in hearts, human induced pluripotent stem cell-derived cardiomyocytes, and engineered heart tissues, accompanied by alterations in excitation-contraction coupling. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by JAK/STAT inhibition or a mitochondrially targeted antioxidant, indicating that SARS-CoV-2 infection indirectly leads to arrhythmias by innate immune activation and redox stress, which could have implications for long COVID syndrome.},
}

Animals
*COVID-19/complications/immunology/physiopathology
*Immunity, Innate
*Arrhythmias, Cardiac/immunology/physiopathology/etiology/virology
SARS-CoV-2
*Reactive Oxygen Species/metabolism
Humans
*Heart Conduction System/physiopathology/immunology
Cricetinae
Disease Models, Animal
Male
Myocytes, Cardiac/metabolism/immunology
*Mitochondria/metabolism
Cytokines/metabolism
Electrocardiography
Poly I-C

@article {pmid41421320,
year = {2025},
author = {Soares, L and Davis, H and Spier, E and Walker, T and Davenport, T and Putrino, D and Peluso, M and Vogel, JM},
title = {Recommended long COVID outcome measures and their implications for clinical trial design, with a focus on post-exertional malaise.},
journal = {EBioMedicine},
volume = {123},
number = {},
pages = {106083},
doi = {10.1016/j.ebiom.2025.106083},
pmid = {41421320},
issn = {2352-3964},
abstract = {Long COVID has created a worldwide public health crisis and has no approved treatments or validated biomarkers. We summarize the current challenges and considerations of outcome selection in Long COVID trials, along with recommendations for current trial design and future endpoint validation, with a focus on post-exertional malaise (PEM). We make five overarching recommendations for Long COVID clinical trials: 1) thorough characterisation of baseline disease; 2) collection of longitudinal data; 3) design of a placebo arm to enable comparison of treatment effect relative to the disease natural history; 4) accounting for, and when feasible, measuring PEM; 5) balancing severity, duration, and relevant phenotypes across trial arms and within subgroups to be analysed. We present a list of outcomes that may be considered for Long COVID clinical trials, with a focus on PEM. Crucially, the field of Long COVID clinical trials urgently needs funding and research effort investment to develop and validate outcomes concomitantly with clinical trial research.},
}

@article {pmid41418608,
year = {2025},
author = {Sinclair, JE and Mayfield, HJ and Lu, H and Brown, SJ and Moghaddam, T and Waller, M and Bonner, C and Williams, O and Litt, JCB and Short, KR and Lau, CL},
title = {Estimating risk of long COVID using a Bayesian network-based decision support tool.},
journal = {Vaccine},
volume = {72},
number = {},
pages = {128127},
doi = {10.1016/j.vaccine.2025.128127},
pmid = {41418608},
issn = {1873-2518},
abstract = {IMPORTANCE: Long COVID causes substantial health burden globally, affecting over 30 % of adults who have ever had symptomatic COVID-19. Individuals at continued risk of long COVID need better and more accessible information to make choices about vaccines and treatments.

OBJECTIVE: To quantify modifiable risk factors for having long COVID six months post-infection, and develop a decision support tool for managing the risk factors.

A Bayesian network (BN) model was developed to estimate the probability of long COVID depending on demographics (sex, age), comorbidities, and modifiable factors (vaccination history, number of previous SARS-CoV-2 infections, and drug treatments during acute infection). Data were sourced from published studies and government reports.

Outcome measures include probability of hospitalisation, ICU admission, and dying from COVID-19 during the acute infection under different scenarios of demographics, comorbidities, vaccine coverage and effectiveness. The BN also estimates the risk of developing long COVID depending on modifiable risk factors, and persistent symptoms related to specific systems (cardiovascular, gastrointestinal, musculoskeletal, pulmonary, neurological, renal, metabolic, coagulation, fatigue, and mental health).

RESULTS: Vaccination, receiving drug treatment within three days of acute infection, and avoiding repeated infections are the greatest modifiable influences of long COVID development, decreasing risk by up to 63 % under modelled scenarios. The interactive user-friendly web-based decision support tool (https://corical.immunisationcoalition.org.au/longcovid) enables easy access to model outputs, and allows individuals to calculate their personalised probability of long COVID under different scenarios of modifiable risk factors.

CONCLUSIONS AND RELEVANCE: The decision-support tool can be used by individuals or in conjunction with clinicians for shared decision-making on vaccination, pursuing early drug treatment during acute infection, and continuing protective behaviors such as masking and social distancing. The model can also generate population-level estimates of outcomes to assist public health decision-makers to design better-informed public health policies.},
}

@article {pmid41415584,
year = {2025},
author = {Kvandova, M and Balis, P and Kalocayova, B and Vlkovicova, J and Dobrodenkova, S and Puzserova, A},
title = {Cardiovascular damage and comorbidities related to long COVID: pathomechanisms, prevention, and therapy.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1671951},
pmid = {41415584},
issn = {2297-055X},
abstract = {Long COVID (LC) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems, including cardiovascular. Extensive literature supports an association between SARS-CoV-2 infection and cardiovascular complications and increased cardiovascular risk after infection. The cardiovascular sequelae after SARS-CoV-2 infection have not yet been comprehensively characterized. A growing body of evidence suggests that endothelial dysfunction is a central mechanism in COVID-19 and has also been identified as a key pathogenic mechanism in LC. Although considerable progress has been made in characterizing the epidemiology, clinical course, and biology of LC, many questions remain unanswered. The incomplete understanding of the pathomechanisms of LC has hampered the development of targeted therapies to date. Further research and data are needed to develop effective therapeutic and preventive tools. Based on current literature this review aims to provide an up-to-date overview of the pathomechanisms affecting the cardiovascular system and the potential role of selected micronutrients, vitamins and minerals, and flavonoids as preventive and therapeutic strategies in LC.},
}

@article {pmid41413915,
year = {2025},
author = {Gouraud, C and Ancellin-Geay, A and Verot, C and Bergeras, I and Poudevigne, L and Cormier, L and Gilbert, S and Limosin, F and Lacoste, L and Ribayrol, D and Vedrines, CO and Pitron, V and Mesbahi-Ihadjadene, K and Abdoul, H and Rousseau, J and Kachaner, A and Ranque, B and Thoreux, P and Lemogne, C},
title = {Cognitive behavioral therapy, exercise training, and cognitive remediation for patients with post-COVID-19 condition: protocol of an open-label randomized controlled trial.},
journal = {BMC psychology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40359-025-03820-8},
pmid = {41413915},
issn = {2050-7283},
support = {AAP CoVID-1//Assistance Publique - Hôpitaux de Paris/ ; },
}

@article {pmid41413539,
year = {2025},
author = {Nielsen, TB and Oestergaard, LG and Hawkins, J and Nielsen, CV and Leth, S and Laursen, CH and Sørensen, D},
title = {How a long COVID rehabilitation intervention works: refining its programme theory through a realist-informed qualitative study.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-025-13916-x},
pmid = {41413539},
issn = {1472-6963},
abstract = {BACKGROUND: Although the majority of individuals infected with SARS-CoV-2 recover without treatment, some individuals experience persistent symptoms (long COVID), which may negatively affect their activities and roles of everyday life, leaving them with a profound rehabilitation need. In response to the emergence of long COVID patients, a Danish municipality developed and implemented a structured, out-patient long COVID rehabilitation intervention (The Long COVID Rehabilitation Intervention). To understand how, why and for whom the intervention works, and its functioning, an exploration of the underlying programme theory is required. We thus aimed to explore the interactions between the intervention mechanisms of change, the implementation context and the expected outcomes of The Long COVID Rehabilitation Intervention to confirm or refine the initial programme theory.

METHODS: We conducted a qualitative study from a realist perspective. Data comprised 12 individual interviews with patients participating in the intervention, a focus group interview with the health professionals delivering the intervention, and an individual interview with the manager of the rehabilitation centre. Transcripts were coded and analysed using a realist analytical approach, enabling for refinement of the initial programme theory expressed with context-mechanism-outcome configurations.

RESULTS: We demonstrated a close interconnectedness among the context-mechanism-outcome configurations, with identity transformation as central to the intervention functioning supported by a person-centred rehabilitation approach, patient education, and peer support. Moreover, we identified acceptance as an overarching mechanism across all context-mechanism-outcome configurations, facilitating a reconceptualisation of beliefs, values, and roles. This empowered the patients to navigate and participate in daily life despite ongoing long COVID symptoms.

CONCLUSION: Overall, the initial programme theory was confirmed but required refinement to contexts and mechanisms. The theorisation of The Long COVID Intervention clarified how, why, and for whom it worked, informing the development of future long COVID and post-viral rehabilitation interventions.},
}

@article {pmid41413200,
year = {2025},
author = {Yang, S and Datta, D and Krienen, FM and Woo, E and May, A and Anderson, GM and Galvin, VC and Gonzalez-Burgos, G and Lewis, DA and Ling, E and McCarroll, SA and Arnsten, AF and Wang, M},
title = {Kynurenic acid signaling expands in human and nonhuman primates and impairs dorsolateral prefrontal cortical cognition that is key to mental illness.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41413200},
issn = {1476-5578},
support = {RF1 AG083090/AG/NIA NIH HHS/United States ; 2015276//National Science Foundation (NSF)/ ; },
abstract = {Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, where impairments are correlated with kynurenine inflammatory signaling. Kynurenine synthesis from tryptophan is increased under conditions of inflammation, then further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may contribute to higher cognitive deficits in these disorders. The current study employed several methods to examine the expression of KYNA and its synthetic enzyme, KAT II, in primate dlPFC, and to determine its effects on working memory-related dlPFC neuronal firing and cognitive functioning in aging macaques with naturally-occurring neuroinflammation. We found that KYNA, its synthetic enzyme, KAT II, and the gene encoding KAT II (AADAT), have greatly expanded expression in macaque and human dlPFC in both glia and neurons, with AADAT especially prominent in primate neurons compared to rodent PFC. In macaques, like humans, plasma kynurenine/tryptophan ratios increased with age, consistent with age-related increasing inflammation. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys. These data show that KYNA inflammatory signaling expands in primate dlPFC, and that inhibition of kynurenine-KYNA production may provide a powerful therapeutic avenue for treating higher cognitive deficits in neuroinflammatory disorders.},
}

@article {pmid41412286,
year = {2025},
author = {Zahiriharsini, A and Rostami, M and Hurd, C and Vakilian, F and Brar, G and Wang, T and Mullie, T and Basiuk, S and Mann, B and Castilho, CD and Smith, M and Lam, G and Ho, C and Manhas, KP},
title = {Evaluating medical and rehabilitation programs for long COVID: utilization, health outcomes, and healthcare costs.},
journal = {The American journal of the medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjms.2025.12.780},
pmid = {41412286},
issn = {1538-2990},
abstract = {BACKGROUND: Long COVID presents a substantial and evolving challenge to individuals and health systems. Despite growing interest in interdisciplinary care models, empirical evidence on their structure, utilization, and effectiveness remains limited. This study examined the delivery and outcomes of specialized outpatient programs for long COVID in Alberta, Canada, focusing on: (a) patterns of program utilization; (b) patient-reported health outcomes; and (c) impacts on healthcare system utilization and costs.

METHODS: A retrospective observational study was conducted using administrative health records, electronic medical records, and patient-reported outcome measures (PROMs) between April 2022 and September 2023. Adults (≥18 years) with persistent symptoms ≥12 weeks post-infection were included. Healthcare utilization and costs were assessed over 180-day pre- and post-enrollment periods. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER).

RESULTS: Of 2819 referrals, 81% (n = 2287) were accepted. Most patients were female (68%), aged 48.2 years on average, and referred by community physicians. Site-level differences were observed in staffing models, care delivery modalities, and wait times. Following enrollment, patients reported small but statistically significant improvements in functional status and quality of life. Symptoms of depression, as measured by the PHQ-9, decreased by an average of 0.9 points (p < 0.05), though below thresholds for clinical significance. Anxiety levels, assessed by the GAD-7, did not change significantly. EQ-5D VAS scores improved by 4.6 points (p = 0.003). Modest reductions in inpatient, ambulatory, and physician service costs were observed. The ICER was $31,140 per quality-adjusted life year (QALY), approaching the Canadian cost-effectiveness threshold.

CONCLUSIONS: In this observational analysis, program participation was associated with small improvements in patient-reported health status and modest cost patterns. Because natural recovery, regression to the mean, and concurrent system changes may also explain these trends, the findings should be interpreted as preliminary associations rather than causal effects. Prospective controlled studies are needed to confirm effectiveness and economic value.},
}

@article {pmid41411839,
year = {2025},
author = {Calik, I and Peker, Y},
title = {REM - predominant obstructive sleep apnea in adults with a history of COVID-19 infection: A case-control study.},
journal = {Sleep medicine},
volume = {139},
number = {},
pages = {108729},
doi = {10.1016/j.sleep.2025.108729},
pmid = {41411839},
issn = {1878-5506},
abstract = {STUDY OBJECTIVES: An association between COVID-19 and obstructive sleep apnea (OSA) has been reported in literature. We aimed to address the occurrence and phenotypes of OSA in adults with a history of COVID-19 infection and its possible association with long-COVID.

METHODS: In this matched case-control study, 152 individuals with a history of COVID-19 and 152 without were evaluated in a sleep laboratory. Groups were matched for age, sex, and body mass index. OSA was defined as an apnea-hypopnea index (AHI) ≥15/h. Rapid Eye Movement (REM)-predominant OSA was defined as AHI ≥15/h and REM-AHI/non-REM-AHI ≥2. Fatigue, reported as "frequent/very frequent," was used as a surrogate marker of long-COVID.

RESULTS: The prevalence of OSA was significantly lower in the case group (50.0 %) compared to the control group (77.6 %) (p < 0.001). However, 36 cases (47.4 %) exhibited REM-predominant OSA while 21 controls (17.8 %) demonstrated this phenotype (p < 0.001). In a multiple logistic regression analysis, there was a significant correlation between prior COVID-19 infection and the occurrence of REM-predominant OSA (Odds ratio [OR] 3.14; 95 % confidence interval [CI] 1.89-5.25; p < 0.001). Fatigue was observed in 52.8 % of patients with REM-predominant OSA and 35.7 % of patients without REM-predominant OSA (p = 0.033). In the entire cohort, the factors determining the fatigue were female sex (OR 2.02; 95 % CI 1.12-3.64, p = 0.019) and REM-predominant OSA (OR 2.18; 95 % CI 1.29-3.69; p = 0.004).

CONCLUSIONS: REM-predominant OSA is highly prevalent among individuals with prior COVID-19 infection and is significantly associated with fatigue, underscoring the need to recognize this phenotype in the evaluation and management of Long-COVID.},
}

@article {pmid41410771,
year = {2025},
author = {Petrova, B and Syphurs, C and Culhane, AJ and Chen, J and Chen, E and Cotsapas, C and Esserman, D and Montgomery, RR and Kleinstein, SH and Smolen, KK and Mendez, K and , and Lasky-Su, J and Steen, H and Levy, O and Diray-Arce, J and Kanarek, N},
title = {MTHFR allele and one-carbon metabolic profile predict severity of COVID-19.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {51},
pages = {e2509118122},
pmid = {41410771},
issn = {1091-6490},
support = {AI118608//HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases (DMID)/ ; AI089992//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {Humans ; *COVID-19/genetics/metabolism/blood ; *Methylenetetrahydrofolate Reductase (NADPH2)/genetics/metabolism ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Severity of Illness Index ; *Carbon/metabolism ; Alleles ; *Metabolome ; Metabolomics ; Aged ; Adult ; Methionine/metabolism ; },
abstract = {While the public health burden of SARS-CoV-2 infection has lessened due to natural and vaccine-acquired immunity, emergence of less virulent variants, and antiviral medications, COVID-19 continues to take a significant toll. There are thousands of new hospitalizations and hundreds of deaths per week in the United States, many of whom develop long COVID. Early identification of individuals at high risk of severe COVID-19 is key for monitoring and supporting respiratory status and improving outcomes. Therefore, precision tools for early detection of patients at high risk of severe disease can reduce morbidity and mortality. Here, we report an untargeted, longitudinal plasma metabolomics study of COVID-19 patients. One-carbon metabolism, a pathway previously shown as critical for viral propagation and disease progression, and a potential target for COVID-19 treatment, scored strongly as differentially abundant in patients with severe COVID-19. Targeted metabolite profiling revealed that one arm of the one-carbon metabolism pathway, the methionine cycle, is a major driver of the metabolic profile associated with disease severity. Further, genomic data from the profiled patients revealed a genetic contributor to methionine metabolism and identified the C677T allele of the MTHFR gene as a preexisting contributor to disease trajectory-patients that show aberrant one-carbon metabolite levels and that are homozygous for the MTHFR C677T, have higher incidence of severe COVID. Our results raise the possibility that MTHFR variant status may inform precision COVID-19 treatment strategies.},
}

Humans
*COVID-19/genetics/metabolism/blood
*Methylenetetrahydrofolate Reductase (NADPH2)/genetics/metabolism
Male
Female
Middle Aged
SARS-CoV-2
Severity of Illness Index
*Carbon/metabolism
Alleles
*Metabolome
Metabolomics
Aged
Adult
Methionine/metabolism

@article {pmid41408839,
year = {2026},
author = {Pasternak Taschner, N},
title = {Social long COVID: impacts of the COVID-19 pandemic on public health and policy in Brazil.},
journal = {International journal of epidemiology},
volume = {55},
number = {Supplement_1},
pages = {i44-i45},
pmid = {41408839},
issn = {1464-3685},
}

@article {pmid41408718,
year = {2025},
author = {Ryu, S and Slocum, EM and Whittington, B and Arciniega, LZ and Ahmed, S and Fleischer, NL},
title = {Prospective Associations of Long COVID with Sleep Health Nearly 3 Years After SARS-CoV-2 Infection: A Statewide Representative Cohort Study.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf405},
pmid = {41408718},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: While many adults with Long COVID experience sleep problems, the long-term relationship between Long COVID and sleep remains poorly understood. We investigated how Long COVID is prospectively associated with sleep duration, sleep quality, and sleep disturbance using a population-based cohort of Michigan adults with COVID-19 (n=2,406).

METHODS: Long COVID was defined at baseline as reporting a recovery time of 90 days or more after the initial infection and sleep outcomes were assessed at follow-up 1 and 2, approximately 1.5 years and 3 years after the initial infection. We estimated linear and multinomial logistic regression models with sleep duration as continuous and categorical variables, respectively. Then, we conducted multinomial logistic regression models for sleep quality and modified Poisson regression for moderate-to-severe sleep disturbance.

RESULTS: Long COVID was prospectively associated with a shorter sleep duration by 0.35 hours (95% CI: -0.53, -0.17) at follow-up 1. Relative to sleeping 6-9 hours, Long COVID was associated with sleeping <6 hours at follow-up 1 (aRRR: 3.27; 95% CI: 2.16, 4.96) and follow-up 2 (aRRR: 1.91; 95% CI: 1.28, 2.85). Additionally, Long COVID had a strong association with poor-to-very poor sleep quality at both follow-up periods relative to very good-to-fair sleep quality at both follow-up periods. Long COVID was also associated with a 1.53 times higher risk of moderate-to-severe sleep disturbance (95% CI: 1.23, 1.91).

CONCLUSION: Long COVID was prospectively associated with unhealthy sleep outcomes 3 years after onset. There is a need to enhance sleep health among individuals with Long COVID.},
}

@article {pmid41407606,
year = {2025},
author = {Ouksel, H},
title = {[Long covid pulmonary rehabilitation].},
journal = {Revue des maladies respiratoires},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.rmr.2025.12.001},
pmid = {41407606},
issn = {1776-2588},
abstract = {While the SARS-CoV-2 pandemic has left a lasting impression, the long-term effects of this virus, such as persistent symptoms or long COVID, remain unclear. However, recommendations from learned societies for improving these symptoms exist and are being applied by a number of respiratory rehabilitation centers. In this paper, we provide a summary of the specificities of long COVID care in the context of respiratory rehabilitation, particularly as regards respiratory symptoms, fatigue, cognitive disorders, and cardiovascular symptoms and, more specifically, vegetative dysautonomia. The key elements of support are Therapeutic Patient Education (TPE) and activity management and fractionated exercise (PACING). While the effects of respiratory rehabilitation are highly promising, with potential improvement in symptoms and exercise capacity, the level of evidence remains low to moderate. Structured and coordinated multidisciplinary work is of paramount importance as a means of providing for these individuals the best possible support on their road to recovery. Further studies are needed to improve the level of evidence on the effectiveness of rehabilitation in cases of long COVID.},
}

@article {pmid41407484,
year = {2025},
author = {Wilson, JC and Liu, KY and Mittelman, E and Bareke, P and Shleifer, E and Howard, R},
title = {Brain fog with long covid and chemotherapy: systematic review and meta-analysis.},
journal = {BMJ mental health},
volume = {28},
number = {1},
pages = {},
pmid = {41407484},
issn = {2755-9734},
mesh = {Humans ; *COVID-19/complications/psychology ; *Antineoplastic Agents/adverse effects ; *Neoplasms/drug therapy ; SARS-CoV-2 ; *Cognitive Dysfunction/etiology ; },
abstract = {QUESTION: What are the cognitive, functional and affective characteristics of brain fog in individuals with long covid and following chemotherapy, and how are these features assessed across studies?

STUDY SELECTION AND ANALYSIS: In March 2024, we conducted a systematic review and meta-analysis of peer-reviewed studies assessing cognition, function or mood in adults (≥18 years) with brain fog after COVID-19 or chemotherapy. PubMed, Embase and Web of Science were searched systematically according to eligibility criteria to March 2024, with an update in May 2025. Random-effects meta-analyses using the 'dmetar' package (V.0.0.9000) in R V.4.3.1 were performed for studies comparing individuals with and without brain fog. Bias was assessed using the National Institutes of Health Study Quality Assessment Tools.

FINDINGS: Of 3077 records screened, 65 studies met inclusion criteria: 40 investigated brain fog in long covid and 25 in chemotherapy populations. Considerable variation in assessment tools was observed. Montreal Cognitive Assessment was the most common cognitive test in long covid studies; Functional Assessment of Cancer Therapy-Cognitive Function was most used in chemotherapy studies. Nine long covid studies were eligible for meta-analysis. Compared with controls, individuals with brain fog had significantly lower cognitive performance (Hedge's g=-0.63, 95% CI -1.15 to -0.12), higher fatigue (Hedge's g=2.64, 95% CI 0.41 to 4.86) and more depressive symptoms (Hedge's g=1.48, 95% CI 0.40 to 2.55). Heterogeneity was high (I[2]>70%). No chemotherapy studies were appropriate for meta-analysis, preventing direct comparison of brain fog features between long covid and chemotherapy groups.

CONCLUSIONS: Brain fog in long covid and chemotherapy populations is associated with cognitive complaints, fatigue and mood disturbance, though assessment methods differ widely. To improve comparability and clinical understanding, we propose adoption of consistent tools and definitions in future studies. This will be a crucial step in generating findings that can be meaningfully compared across populations.

PROSPERO REGISTRATION NUMBER: CRD42024520549.},
}

Humans
*COVID-19/complications/psychology
*Antineoplastic Agents/adverse effects
*Neoplasms/drug therapy
SARS-CoV-2
*Cognitive Dysfunction/etiology

@article {pmid41405757,
year = {2025},
author = {Rasouli, R and Hartl, B and D Konecky, S},
title = {Investigation of the synergistic effect of enzymatic and Ultrasound-Induced amyloid microclot degradation.},
journal = {Journal of thrombosis and thrombolysis},
volume = {},
number = {},
pages = {},
pmid = {41405757},
issn = {1573-742X},
abstract = {Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In this study we examine the effects of three fibrinolytic enzymes rtPA, Lumbrokinase, and Nattokinase on plasma-derived amyloid microclots, in combination with ultrasound-induced microstreaming and microbubbles. A lab-on-chip platform was used to expose the clots to ultrasound at 150, 300, and 500 kHz. Quantitative analysis revealed that ultrasound alone significantly disrupted clot structures, particularly at 150 kHz, where mean clot diameter was reduced by over 60% and large-clot count (> 30 μm) dropped by more than 80% compared to controls. The addition of fibrinolytic enzymes, however, did not produce statistically significant effects at 150-300 kHz which indicates that mechanical forces were the dominant contributors to clot disruption. At 500 kHz, where ultrasound alone was less effective, enzymatic treatment moderately enhanced the reduction in large-clot burden. These results show the potential of low-frequency ultrasound as a primary method of amyloid microclot breakdown, with enzyme co-treatment offering limited but measurable effect.},
}

@article {pmid41405529,
year = {2025},
author = {Sawano, M and Spatz, ES and Sanders, L},
title = {Long COVID as Intermediate Physiology: Rethinking Autonomic Dysfunction and Medical Uncertainty.},
journal = {Journal of the American College of Cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacc.2025.10.083},
pmid = {41405529},
issn = {1558-3597},
}

@article {pmid41404601,
year = {2025},
author = {Thapaliya, K and Marshall-Gradisnik, S and Inderyas, M and Barnden, L},
title = {Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study.},
journal = {Brain, behavior, & immunity - health},
volume = {50},
number = {},
pages = {101142},
pmid = {41404601},
issn = {2666-3546},
abstract = {BACKGROUND: Diverse neurological symptoms are experienced by long COVID and COVID-19 recovered individuals. However, the long-term effects of SARS-CoV-2 in the brain of both groups are underexplored. This study aimed to investigate changes in tissue microstructural and brain neurochemical levels in long COVID and recovered COVID-19 patients compared to healthy controls.

METHODS: We recruited 47 participants (long COVID = 19, COVID-recovered healthy controls = 12, and healthy controls without COVID-19 infection = 16) who underwent 3T MRI scans. We acquired T1 and T2 weighted images to assess myelin signal, diffusion weighted images to assess tissue microstructure, and magnetic resonance spectroscopy data to estimate brain neurochemical levels.

FINDINGS: Our multimodal MRI study showed altered T1w/T2w signal between long COVID vs COVID-recovered-healthy controls, long COVID vs healthy controls, and COVID-recovered-healthy controls vs healthy controls. Furthermore, T1w/T2w signal intensity was significantly correlated with physical and cognitive function. Diffusion weighted imaging also showed altered tissue microstructure in these three group comparisons. However, brain neurochemicals were only significantly different between long COVID vs COVID-recovered-healthy controls.

INTERPRETATION: This is one of the first studies to report different myelin signal and brain neurochemical changes between long COVID, COVID-recovered-healthy controls, and healthy controls without SARS-CoV-2 infection. These brain changes provide compelling evidence for the long-term effects of SARS-CoV-2 on brain function.},
}

@article {pmid41402665,
year = {2025},
author = {Schuermans, A and Verstraete, A and Lammi, V and Nakanishi, T and Ardissino, M and Van den Eynde, J and Sun, BB and Georgakis, MK and Guillen-Guio, B and Wain, LV and Brightling, CE and , and Van Weyenbergh, J and Lewandowski, AJ and Raman, B and Zeberg, H and Ollila, HM and Burgess, S and Natarajan, P and Honigberg, MC and Freson, K and Vanassche, T and Verhamme, P},
title = {Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry.},
journal = {Nature cardiovascular research},
volume = {4},
number = {12},
pages = {1662-1676},
pmid = {41402665},
issn = {2731-0590},
support = {22J30004//Japan Society for the Promotion of Science London (JSPS London)/ ; 512461526//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 302210/Z/23/Z//Wellcome Trust (Wellcome)/ ; 221680/Z/20/Z//Wellcome Trust (Wellcome)/ ; #1350181//Academy of Finland (Suomen Akatemia)/ ; R01AI170850//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01Hl161365//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; C14/23/121//KU Leuven (Katholieke Universiteit Leuven)/ ; G072921N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 1843423N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 2021-03050//Vetenskapsrådet (Swedish Research Council)/ ; 2023.0141//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; },
mesh = {Female ; Humans ; Male ; Middle Aged ; *COVID-19/genetics/complications/ethnology ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Risk Factors ; *Venous Thromboembolism/genetics ; *White People/genetics ; },
abstract = {SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organs. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and thromboembolism; however, compelling evidence from humans is limited and causal associations remain unclear. In this study, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative (ncases = 3,018; ncontrols = 994,582). Primary analyses revealed that each unit increase in the log odds of genetically predicted venous thromboembolism risk was associated with 1.21-fold odds of long COVID (95% confidence interval (CI): 1.08-1.35; P = 1.2 × 10[-3]). This association was independent of acute COVID-19 severity, was robust across various sensitivity analyses and was replicated in external datasets. Downstream analyses using gene-specific instruments, along with protein and gene expression data, suggested the protease-activated receptor 1 (PAR-1) as a potential molecular contributor to long COVID. These findings provide human genetic evidence implicating shared pathogenetic pathways in thromboembolism and long COVID.},
}

Female
Humans
Male
Middle Aged
*COVID-19/genetics/complications/ethnology
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Risk Factors
*Venous Thromboembolism/genetics
*White People/genetics

@article {pmid41402664,
year = {2025},
author = {Denorme, F and Campbell, RA},
title = {Linking thromboembolism to the pathogenesis of long COVID.},
journal = {Nature cardiovascular research},
volume = {4},
number = {12},
pages = {1594-1595},
pmid = {41402664},
issn = {2731-0590},
}

@article {pmid41397681,
year = {2025},
author = {Kouyoumdjian, JA and Yamamoto, LAR and Graca, CR},
title = {Reply to the letter "Long-COVID may not be explained by skeletal muscle involvement, but rather by other, more compelling pathophysiological concepts".},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {10},
pages = {1-2},
doi = {10.1055/s-0045-1812889},
pmid = {41397681},
issn = {1678-4227},
}

@article {pmid41397680,
year = {2025},
author = {Finsterer, J and Scorza, FA and Scorza, CA},
title = {Long COVID may not be explained by skeletal muscle involvement, but rather by other, more compelling pathophysiological concepts.},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {10},
pages = {1-2},
doi = {10.1055/s-0045-1809404},
pmid = {41397680},
issn = {1678-4227},
}