@article {pmid41451962,
year = {2025},
author = {Ros, JPUD and Ros, LUD and Bieger, A and Silveira, MD and Borelli, WV and Senger, JE and Machado, LS and Ferrari-Souza, JP and Bastiani, MA and Povala, G and da Silva, APB and de Mello, GB and Jotz, AV and Kadan, MF and Radaelli, G and de Paula Faria, D and Coutinho, AM and Lourenco, MV and Pascoal, TA and Rosa-Neto, P and Matushita, CS and Soder, RB and Schumacher-Schuh, AF and Souza, DO and da Costa, JC and de Souza, DG and Zimmer, ER},
title = {Clinical Manifestations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 3},
number = {},
pages = {e106936},
doi = {10.1002/alz70857_106936},
pmid = {41451962},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; *COVID-19/complications/psychology ; Magnetic Resonance Imaging ; Middle Aged ; *Gray Matter/pathology/diagnostic imaging ; Brazil ; *Hippocampus/pathology/diagnostic imaging ; *Depression/etiology ; Adult ; *Anxiety ; Aged ; SARS-CoV-2 ; *Cerebral Cortex/pathology/diagnostic imaging ; *Brain/diagnostic imaging/pathology ; },
abstract = {BACKGROUND: Neurological manifestations in individuals with Long COVID range from headaches to cognitive impairment and mental health issues. However, it remains unclear whether these individuals exhibit structural changes, functional changes, or both in the brain. In this study, we investigated the impact of Long COVID on mental health symptoms, cortical grey matter volume and thickness, and hippocampal volume in Brazilian individuals.

METHOD: Individuals were divided into two groups based on Long COVID status: covid (symptoms of Long COVID) and control (No symptoms of Long COVID). Simultaneously, PHQ-9 and GAD-7 tests were applied on participants to evaluate severity of depression and generalized anxiety symptoms, respectively. Brain magnetic resonance imaging (MRI) of individuals presenting with Long COVID (n = 58) and of healthy control individuals (n = 21) were used for extracting volume and cortical thickness (CT) of regions of interest using FreeSurfer (v7.4.1). We performed an ANCOVA analysis and a linear regression to assess the difference between groups in PHQ-9, GAD-7, mean cortical thickness (CT), mean hippocampal volume, and total cortical grey matter volume. The data were corrected for age, sex, and years of formal education.

RESULT: The Long Covid group presented significantly lower scores on PHQ-9 and GAD-7 than the control group (Beta = 6.20017 and 3.3105; p <0,001 and p <0,006, respectively). However, when comparing Long covid and control groups, we found no significant differences in the mean hippocampal volume (p = 0,831) and in the mean cortical grey matter volume (p = 0.193).

CONCLUSION: These preliminary data indicate significant changes in mental health among individuals with Long Covid; however, these changes do not correspond to observable alterations in brain volume as seen in MRI scans. This suggests that the pathophysiological changes associated with these symptoms are likely functional and metabolic in nature rather than structural and may not be detectable through imaging studies that primarily focus on brain anatomy, such as MRI.},
}

Humans
Male
Female
*COVID-19/complications/psychology
Magnetic Resonance Imaging
Middle Aged
*Gray Matter/pathology/diagnostic imaging
Brazil
*Hippocampus/pathology/diagnostic imaging
*Depression/etiology
Adult
*Anxiety
Aged
SARS-CoV-2
*Cerebral Cortex/pathology/diagnostic imaging
*Brain/diagnostic imaging/pathology

@article {pmid41451554,
year = {2025},
author = {Kehl-Floberg, KE and Pop-Vicas, A and Edwards, DF},
title = {Clinical Manifestations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 3},
number = {},
pages = {e105712},
doi = {10.1002/alz70857_105712},
pmid = {41451554},
issn = {1552-5279},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Female ; Cross-Sectional Studies ; *Cognitive Dysfunction/diagnosis/etiology ; Aged ; Neuropsychological Tests ; Middle Aged ; SARS-CoV-2 ; Self Report ; Cohort Studies ; Aged, 80 and over ; Adult ; },
abstract = {BACKGROUND: Neurocognitive symptoms are among the most debilitating features of long COVID (persistent, ongoing symptoms and conditions following SARS-CoV-2 infection). Traditional neurocognitive screening instruments have been found to be non-sensitive to post-COVID cognitive impairments, often described as 'brain fog', that disrupt performance of complex daily routines. Accurate screening and diagnosis of cognitive impairment is therefore a critical area of clinical research for people with long COVID. We examined whether self-reported or neuropsychological cognitive function tests were more strongly associated with long COVID.

METHODS: In a sample from a community-engaged cross-sectional cohort study, we fitted a binary logistic regression model for the outcome of long COVID status (having history of COVID illness, plus a Post-COVID Functional Status Scale (PCFS) score >=2), classified by MoCA cut score weighted for race/ethnicity, and associated with the Patient-Reported Outcomes Measurement Information System (PROMIS) 8-item Cognitive Functioning t-scores, controlling for age.

RESULTS: We analyzed data from N = 174 participants (n = 67 cases, n = 107 controls). Our final model was fitted with 5-knot natural cubic splines for age and PROMIS Cognition scores. At a "Non-impaired" score on the MoCA, a PROMIS t-score at the lower quartile of 36.67 increased the odds of having long COVID by over seven times at age 25 (1.0,56.89, p = 0.01), over five times at ages 45 (1.4,18.6, p = 0.001) and 55 (1.4,20.4, p = 0.002), and six times at ages 65 (0.9,51.2, p = 0.02) and 75 (0.8,48.9, p = 0.03). By contrast, scores above and below race/ethnicity-weighted MoCA cut score did not significantly affect the odds of having long COVID at any age (p value ranges 0.22-0.25 and 0.19-0.22, respectively) adjusted for mean PROMIS score.

CONCLUSION: Across ages, low PROMIS Cognitive Function scores showed between five- and six-fold increases in odds of long COVID, adjusted for age and MoCA score. This self-rated cognitive function scale was the best predictor of functional status changes attributed to post-COVID-19 health changes in our sample.},
}

Humans
*COVID-19/complications/psychology
Male
Female
Cross-Sectional Studies
*Cognitive Dysfunction/diagnosis/etiology
Aged
Neuropsychological Tests
Middle Aged
SARS-CoV-2
Self Report
Cohort Studies
Aged, 80 and over
Adult

@article {pmid41449436,
year = {2025},
author = {Shan, D and Holland, C and Crawford, T},
title = {Dementia Care Research and Psychosocial Factors.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 4},
number = {},
pages = {e101300},
doi = {10.1002/alz70858_101300},
pmid = {41449436},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; *Dementia/psychology/therapy ; Qualitative Research ; Adolescent ; Young Adult ; *COVID-19/psychology/complications ; Quality of Life/psychology ; *Patient Preference/psychology ; Aged, 80 and over ; *Cognitive Dysfunction/psychology/therapy ; China ; Interviews as Topic ; },
abstract = {BACKGROUND: Long COVID-associated cognitive impairments significantly diminish patients' quality of life. However, there is a lack of research exploring patient perspectives on treatment preferences and expectations, especially across age groups.

METHOD: In this qualitative study, we employed a constructivist grounded theory approach. Semi-structured online interviews were conducted with 23 Chinese participants, comprising 10 young adults (aged 18-39 years) and 13 older adults (aged ≥60 years).

RESULT: A central theoretical framework of 'Individualized and Dynamic Adaptation to Cognitive Challenges' was developed, illustrating how factors including age, severity of cognitive symptoms, economic affordability, accessibility of medical resources, prior management experiences regarding cognitive symptoms, baseline health status, personal lifestyle, interests, and attitudes, doctor-patient interactions, and health literacy shaped participants' preferences and expectations. 'Preference for non-pharmacological interventions' emerged as the core theme for young adults, consisting of subthemes including self-directed strategies (formed by concepts such as psychological adaptation and practical tools like to-do lists and alarms) and emotional and psychological support. In contrast, 'balanced use of pharmacological interventions' was identified as the core theme for older adults, consisting of non-pharmacological interventions (formed by concepts such as family support and structured and predictable routines), pharmacological interventions, and holistic expectations (formed by the concept that address not only cognitive but also physical and emotional well-being). Across both age groups, improving sleep quality and psychological well-being was consistently highlighted as essential for effective management. Disrupted sleep was viewed not only as a symptom but also as a factor that could exacerbate cognitive symptoms. For older adults, the need for psychological support often stemmed from poorer baseline health and feelings of neglect and isolation due to limited family presence in daily life. By comparison, young adults expressed a need for emotional care primarily driven by the stigma surrounding long COVID, particularly the perceived lack of trust and understanding from older generations and broader society.

CONCLUSION: Our study is the first to qualitatively explore and compare age-specific treatment preferences, experiences, and expectations regarding long COVID-associated cognitive impairments. By highlighting the heterogeneity of age-specific preferences and expectations, it provides a comprehensive theoretical framework to inform the development of dynamic, patient-centred interventions.},
}

Humans
Male
Female
Middle Aged
Adult
Aged
*Dementia/psychology/therapy
Qualitative Research
Adolescent
Young Adult
*COVID-19/psychology/complications
Quality of Life/psychology
*Patient Preference/psychology
Aged, 80 and over
*Cognitive Dysfunction/psychology/therapy
China
Interviews as Topic

@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 {pmid41447709,
year = {2025},
author = {Frontera, JA and Masurkar, AV and Vedvyas, A and Betensky, RA and Boutajangout, A and Bohara, M and Chodosh, J and Hammam, S and Jiang, L and Links, J and Marsh, K and Thawani, S and Vasilchenko, D and Yakubov, A and Ge, Y and Wisniewski, T},
title = {Clinical Manifestations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 3},
number = {},
pages = {e103528},
doi = {10.1002/alz70857_103528},
pmid = {41447709},
issn = {1552-5279},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Female ; Cross-Sectional Studies ; Aged ; *Cognitive Dysfunction/diagnosis/psychology ; Neuropsychological Tests ; Middle Aged ; SARS-CoV-2 ; *Dementia/diagnosis ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: There is a paucity of data comparing neuropsychiatric testing in patients with post-acute COVID-19 symptoms ("long-COVID") to COVID-19 patients without long-term symptoms and to COVID-19 negative controls.

METHOD: We conducted a cross-sectional study of patients with and without prior laboratory-confirmed COVID-19 (COV+ vs COV-), who had no previous history of dementia/cognitive impairment. Long-COVID was defined as subjective symptoms (WHO symptom questionnaire) lasting >1 month after index SARS-CoV-2 infection. All patients underwent UDS3 neuropsychiatric testing and received a formal cognitive diagnosis (with respective etiology following NACC criteria) by a consensus group of physicians blinded to their long-COVID status as: normal, mild-cognitive impairment (MCI), or dementia. Cognitive test scores, CDR, and physician diagnoses were compared between patients with and without long-COVID using Fisher's exact and Mann-Whitney U tests and multivariable logistic regression models were constructed to adjust for differences in age, sex, time from initial COVID diagnosis and number of COVID-19 infections.

RESULT: We enrolled 279 patients: N = 51 (18%) COV-, N = 228 (82%) COV+, N = 122 (44%) with long-COVID, median age 70 years (IQR 63-76), and 62% female. Compared to COV- subjects and COV+ subjects without long-COVID, participants with long-COVID had significantly worse cognitive test results (≥1 cognitive battery abnormal in 64% with long-COVID compared to 46% without, p = 0.003), as well as worse global CDR and CDR sum of boxes scores (26% CDR>0 among long-COVID vs. 6% without long-COVID, p <0.001). Significantly more long-COVID patients were diagnosed with MCI or dementia (25% vs. 6% without long-COVID, p <0.001), including higher proportions with MCI related to Alzheimer's disease (10% vs. 3%, p = 0.038), and MCI related to psychiatric diagnoses (11% vs. 1%, p <0.001). After adjusting for sex, age, time from initial COVID diagnosis and number of COVID-19 infections, long-COVID was associated with significantly higher odds of an MCI diagnosis (aOR 3.5, 95% CI 1.2-10.6, p = 0.025), and specifically MCI due to Alzheimer's (aOR 4.4, 95% CI 1.1-18.3, p = 0.041), but not MCI due to psychiatric disease.

CONCLUSION: Long-COVID patients had significantly worse cognitive test scores and higher rates of MCI (Alzheimer's type) diagnoses compared to both COV- and COV+ subjects without long-COVID symptoms.},
}

Humans
*COVID-19/complications/psychology
Male
Female
Cross-Sectional Studies
Aged
*Cognitive Dysfunction/diagnosis/psychology
Neuropsychological Tests
Middle Aged
SARS-CoV-2
*Dementia/diagnosis
Aged, 80 and over
Post-Acute COVID-19 Syndrome

@article {pmid41447098,
year = {2025},
author = {Palmer, A and Sander, M and Ballard, CG and Lewis, S and Tulloch, S and Inok, A and Aarsland, D and Hampshire, A and Corbett, A},
title = {Clinical Manifestations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 3},
number = {},
pages = {e105276},
doi = {10.1002/alz70857_105276},
pmid = {41447098},
issn = {1552-5279},
mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Female ; Aged ; *Cognitive Dysfunction/etiology/psychology/epidemiology ; Neuropsychological Tests ; Middle Aged ; Quality of Life ; Executive Function ; SARS-CoV-2 ; Cohort Studies ; Surveys and Questionnaires ; Aged, 80 and over ; },
abstract = {BACKGROUND: Long Covid affects at least 9.9% of people. Neuropsychiatric symptoms are common, with cognitive impairment affecting at least 25% of patients. Cognitive deficits impact on individuals' employment, social activity, wellbeing and quality of life. They are also a key risk factor for onward cognitive impairment and dementia particularly in older adults. However, the aetiology of these cognitive symptoms of Long Covid remains relatively poorly understood. This poster reports on baseline data from BEACON, a trial cohort of people with Long Covid, and provides comparative analysis with data from the PROTECT-UK cohort of older adults.

METHOD: 2185 participants with subjective cognitive impairment following Covid-19 infection were recruited to the online BEACON trial. Participants completed demographic and health-related questionnaires including mental health, fatigue and wellbeing. They also completed the validated FLAME cognitive test system of eight cognitive tests of memory, attention and executive function. Descriptive statistics and t-test analysis were used to characterise the BEACON cohort cognitive profile, and regression analyses examined factors associated with cognition. An age-matched dataset was generated from the PROTECT-UK data from participants with no history of Covid-19 for comparative analysis of cognitive performance.

RESULT: Analysis of BEACON cognitive data demonstrated a unique profile of cognitive impairment compared with healthy controls, with particularly marked impairment in memory and executive function in individuals with a history of more severe Covid-19 infection. Regression analysis showed associations of lifestyle factors with cognitive impairment.

CONCLUSION: This analysis provides a detailed cognitive characterisation of patients with Long Covid, highlighting potentially unique cognitive trajectories in these individuals. These findings emphasise the importance of providing clear, specific clinical guidance for detection, monitoring and treatment of cognitive impairment in this patient group.},
}

Humans
*COVID-19/complications/psychology
Male
Female
Aged
*Cognitive Dysfunction/etiology/psychology/epidemiology
Neuropsychological Tests
Middle Aged
Quality of Life
Executive Function
SARS-CoV-2
Cohort Studies
Surveys and Questionnaires
Aged, 80 and over

@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 {pmid41444980,
year = {2025},
author = {Senger, JE and Machado, LS and Silveira, MD and Ferrari-Souza, JP and Bastiani, M and Povala, G and Borelli, WV and de Mello, GB and Ros, JPUD and Jotz, AV and Kadan, MF and Radaelli, G and Pascoal, TA and Matushita, CS and Soder, RB and Schumacher-Schuh, AF and Souza, DO and Lourenco, MV and de Paula Faria, D and Coutinho, A and da Costa, JC and de Souza, DG and Zimmer, ER},
title = {Clinical Manifestations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 3},
number = {},
pages = {e105941},
doi = {10.1002/alz70857_105941},
pmid = {41444980},
issn = {1552-5279},
mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; Female ; Male ; Neuropsychological Tests ; Middle Aged ; Brazil/epidemiology ; *Educational Status ; Aged ; *Cognitive Dysfunction ; SARS-CoV-2 ; Mental Status and Dementia Tests ; Adult ; },
abstract = {BACKGROUND: Long COVID is a chronic condition that persists for at least three months after SARS-CoV-2 infection. It is characterized by a wide range of symptoms, including neurological manifestations. This study aimed to investigate the influence of long COVID on neuropsychological performance in adults with different educational levels, categorized into high and low education groups.

METHOD: We included community-dwelling individuals from Porto Alegre, Brazil. Participants were divided into four groups based on education and long COVID status: Control-Low Education (CLE), Control-High Education (CHE), Long COVID-Low Education (LCOVID_LE), and Long COVID-High Education (LCOVID_HE). High education was defined as having more than 11 years of schooling. Neuropsychological assessments included the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT-B), and the Wechsler Memory Scale (WMS-R). Group differences in neuropsychological performance were analyzed using Analysis of Variance (ANOVA). Post hoc pairwise comparisons were conducted for significant main effects.a A Kruskal Wallis analysis was used for non-parametric tests. Statistical analyses were performed using R software, with a significance threshold set at p <0.05p<0.05.

RESULT: A total of 122 individuals were included, with a mean age of 59.6 years (± 14.9), of whom 73.8% were female. Demographic details are shown in Figure 1. Participants in the CLE group scored significantly lower on the MMSE than the CHE group (p = 0.007). Similarly, the LCOVID_LE group scored significantly lower than the CHE group (p = 0.009). A significant result was found between MMSE and education (p = 0.003) in Kruskal Wallis analysis. However, no significant effects of long COVID were observed in other neuropsychological domains assessed.

CONCLUSION: Our study highlighted the significant interplay between educational attainment, which contributes to cognitive reserve, and the neurological manifestations of long COVID. Higher educational attainment may confer resilience against cognitive decline associated with long COVID. While long COVID was linked to lower global cognitive scores, no specific cognitive domain appeared particularly vulnerable. These findings underscore the importance of prioritizing support for vulnerable populations with low education to promote brain health.},
}

Humans
*COVID-19/psychology/complications/epidemiology
Female
Male
Neuropsychological Tests
Middle Aged
Brazil/epidemiology
*Educational Status
Aged
*Cognitive Dysfunction
SARS-CoV-2
Mental Status and Dementia Tests
Adult

@article {pmid41377983,
year = {2025},
author = {Salinas, TRW and Freeman, S and Richardson, R and Weng, W and Ali, M and van Schoor, A and Viox, E and Nguyen, K and Auger, J and Ketan, R and Gagne, M and Picou, B and Golden, NA and Vaccari, M and Jean, S and Wood, JS and Cohen, J and Johnson, RP and Douek, DC and Niclou, BA and Levit, RD and Moore, IN and Paiardini, M and Raper, J},
title = {Inflammation from mild COVID-19 results in persistent neurological and behavioral changes in rhesus macaques.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41377983},
issn = {2693-5015},
abstract = {Although most SARS-CoV-2 infections result in mild or moderate symptoms not requiring hospitalization, many patients experience persistent symptoms after their initial recovery, a condition termed Post-Acute Sequelae of SARS-CoV-2 infection (PASC). The underlying pathogenesis behind infection associated chronic illnesses, such as PASC, are poorly understood, thus critically limiting the development of therapeutics to prevent or alleviate symptoms. The current study examined the neurocognitive impact of SARS-CoV-2 induced inflammation in a nonhuman primate model. Ten adult rhesus macaques (5 female, 5 male) were monitored before, during, and after recovery from a mild COVID-19 illness (SARS-CoV-2 strain 2019-noCoV/USA-WA1/2020). Macaques exhibited persistent alterations in taste and smell, as well as decreased cognitive flexibility up to 3 months post-infection. Female macaques experienced sleep disturbances, greater stress and poorer autonomic function months after SARS-CoV-2 infection. Importantly, the development of these neurocognitive changes were associated with acute cytokine response to infection and increased microglia activation in brain tissue at 4 months post-infection. These findings suggest a causative link between the inflammatory response to mild COVID-19 symptoms and persistent neurocognitive changes associated with PASC and provide rationale for therapeutic strategies aimed at reducing acute inflammatory responses to the virus.},
}

@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 {pmid41444159,
year = {2025},
author = {Shigaeff, N and Queiroz-Júnior, CM and Barros, TGR and Hottz, ED and Miranda, AS and Costa, VV and de Brito Toscano, EC},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e107215},
doi = {10.1002/alz70855_107215},
pmid = {41444159},
issn = {1552-5279},
mesh = {Humans ; *COVID-19/complications/blood/psychology ; Female ; Male ; Middle Aged ; *Cognitive Dysfunction/blood/etiology ; Neuropsychological Tests ; SARS-CoV-2 ; Membrane Glycoproteins/blood ; Glial Fibrillary Acidic Protein/blood ; Glial Cell Line-Derived Neurotrophic Factor/blood ; Brain-Derived Neurotrophic Factor/blood ; Nerve Growth Factor/blood ; Receptors, Immunologic/blood ; Case-Control Studies ; Aged ; Biomarkers/blood ; Cognition ; },
abstract = {BACKGROUND: COVID-19 is associated with clinically significant symptoms despite the resolution of the acute infection, characterizing a post-COVID-19 syndrome or long COVID-19. Cognitive impairment is among the most common of these symptoms. Recent evidence has demonstrated a close correlation between COVID-19 and neurodegeneration, bringing the potential role of COVID-19 in the future development of dementia into the spotlight. In this scenario, neuroinflammation is emerging as a potential mechanism linking these disorders. We aimed to evaluate the cognitive function and the plasma levels of inflammatory and neurochemistry mediators in individuals with long COVID-19 compared with age- and sex-matched healthy controls (n = 25 per group) younger than 65 years. We also sought to investigate the possible association between these proteins and cognitive impairment.

METHOD: Plasma levels of GFAP, TREM2, CX3CL1, BDNF, GDNF, and NGF were quantified using immunoenzimatic assay (ELISA). Cognitive function was evaluated through a comprehensive neuropsychological battery, comprising digits forward and backward, verbal fluency (animals), Trail Making Test (TMT), Stroop, Hopkins Verbal Learning Test (HVLT), Boston Name Test, and symbol digits. We applied the Mann-Whitney test to compare control with long COVID-19 group, and linear regression to examine the association of plasma proteins with cognitive functions.

RESULT: Both groups had 23 women (92%), and the median age of the controls was 39 (19-52) and 35.1 (21-59) in the long COVID-19 group (p = 0.12). The post-infecction interval was 8.2 (6-12) months. Long COVID-19 individuals had a more severe impairment in the TMT, HVLT, and Stroop tests (Figure 1). In addition, they presented decreased plasma levels of TREM2, CX3CL1, GDNF, and NGF compared with healthy controls (Figure 2). Worse performance in TMT was associated with increased levels of GFAP, GDNF, and NGF; while increased levels of TREM2 and CX3CL1 were associated with better performance in the HVTL (imediated) test. Patients with increased TREM2 levels also got higher scores on the verbal fluency test (Table 1).

CONCLUSION: Changes in glial activity and expression of neurotrophic factors are associated with long COVID-19. Plasma levels of neurochemical mediators may be useful in predicting impairment of frontal cognitive functions.},
}

Humans
*COVID-19/complications/blood/psychology
Female
Male
Middle Aged
*Cognitive Dysfunction/blood/etiology
Neuropsychological Tests
SARS-CoV-2
Membrane Glycoproteins/blood
Glial Fibrillary Acidic Protein/blood
Glial Cell Line-Derived Neurotrophic Factor/blood
Brain-Derived Neurotrophic Factor/blood
Nerve Growth Factor/blood
Receptors, Immunologic/blood
Case-Control Studies
Aged
Biomarkers/blood
Cognition

@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 = {},
doi = {10.3390/metabo15120801},
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 = {},
doi = {10.3390/medsci13040295},
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 = {},
doi = {10.3390/diseases13120391},
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 = {},
doi = {10.3390/epidemiologia6040091},
pmid = {41439849},
issn = {2673-3986},
support = {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 {pmid41437868,
year = {2025},
author = {Frautschy, SA and Manglani, K and Zuo, X and Zhu, C and Bombino, A and Kwon, J and Jones, M and Fraser, D and Cole, GM},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e106266},
doi = {10.1002/alz70855_106266},
pmid = {41437868},
issn = {1552-5279},
mesh = {Animals ; Rats ; Disease Models, Animal ; Humans ; *Alzheimer Disease/pathology ; *Hypertension/pathology ; *COVID-19/pathology ; *Spike Glycoprotein, Coronavirus/metabolism ; Complement Activation ; Apolipoprotein E4/genetics ; Male ; SARS-CoV-2 ; Cerebral Amyloid Angiopathy ; Brain/pathology ; White Matter/pathology ; },
abstract = {BACKGROUND: Most COVID-19 cases fully recover, but 7% report persistent symptoms (Long Covid, LC). SARS-CoV2 uses surface S1 Spike protein to bind ACE2 receptors leading to sustained complement activation. S1 activates endothelial C3, leukocyte attachment and invasion, also observed in atherosclerosis, cerebral amyloid angiopathy (CAA), and hypertension-driven small vessel disease (CSVD). LC patients have elevated plasma AD biomarkers and postmortem evidence of microglial, complement and microvascular pathology. AD patients are at increased risk for Neuro-Covid particularly those with ApoE4 and hypertension. Here we explore modulatory roles of hypertension or ApoE4 on the response to S1 in AD rats.

METHOD: We created rat models with AD or mixed AD (AD with CSVD) with or without ApoE4. Outcomes included executive function, AD pathology, white matter damage and complement activation 6 weeks after subcutaneous injection of recombinant S1. We developed high throughput plasma assays to assess vascular and CNS complement activation from rat models or human Neuro-Covid.

RESULT: Experiment 1: Independent of human ApoE or hypertension, S1 increased plaque and vascular amyloid and amyloid responsive ptau217, microvascular active C3 (C3d) and neuronal and vascular complement C5b-9 terminal attack complex. E4 and hypertension synergized to increase vascular pathology induced by spike. This was accompanied by leukocyte adhesion, including neutrophils. Experiment 2: S1 spike injected 11-13 month rats showed spike-induced executive function deficits and significant increases in the hypertensive FAD rats for beta amyloidogenic APP BACE processing, ptau217 as well as loss of myelin basic protein, an index of white matter damage. We also observed increased cortical active C3, CSF C5a (ELISA), and active C3 in plasma endothelial and astrocyte-derived EV. Pre-existing hypertensive comorbidity potentiated Covid spike effects. The plasma of LC patients with Neuro-Covid showed elevated active C3 in astrocyte and endothelial EV.

CONCLUSION: Spike protein caused robust increases in AD pathology as well as persistent pathogenic CNS and vascular complement activation, associated with synapse loss and BBB damage in rats with pre-existing AD and vascular pathology, a situation found in at least 20 to 30% of our aged population. Scalable assays for Neuro-Covid complement activation should facilitate treatment.},
}

Animals
Rats
Disease Models, Animal
Humans
*Alzheimer Disease/pathology
*Hypertension/pathology
*COVID-19/pathology
*Spike Glycoprotein, Coronavirus/metabolism
Complement Activation
Apolipoprotein E4/genetics
Male
SARS-CoV-2
Cerebral Amyloid Angiopathy
Brain/pathology
White Matter/pathology

@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 {pmid41434981,
year = {2025},
author = {Yang, Y},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e099878},
doi = {10.1002/alz70860_099878},
pmid = {41434981},
issn = {1552-5279},
mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; Cross-Sectional Studies ; Retrospective Studies ; Male ; Female ; Aged ; *COVID-19 Vaccines ; *Public Health ; Middle Aged ; SARS-CoV-2 ; *Vaccination/statistics & numerical data ; Aged, 80 and over ; United States/epidemiology ; *Vaccine Efficacy ; Alzheimer Disease/epidemiology ; },
abstract = {BACKGROUND: COVID-19 vaccines became available in December 2020 to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, individuals with chronic conditions such as Alzheimer's disease and related dementias (ADRD) and mild cognitive impairment (MCI) face heightened risks of COVID-19. These risks include increased vulnerability to COVID-19-related mortality, vaccine breakthrough infections, and long COVID symptoms. These risks are further exacerbated by challenges in adhering to preventive measures and managing clinical chronic conditions. Furthermore, the effectiveness of vaccines may decline over time, necessitating ongoing strategies to maintain protection.

METHOD: A retrospective cross-sectional study was conducted utilizing data from the All of Us Researcher Workbench. We extracted relevant data fields on participants' demographic information, social determinants of health, and electronic health records (EHR). COVID-19 vaccination data, including vaccination dates, vaccine brands and doses were collected from EHR drug records between December 14, 2020 and July 1, 2022. Vaccine effectiveness was assessed by examining the duration of immunity from the second dose of vaccination to reported COVID-19 clinical conditions and laboratory results of SARS-CoV-2 (COVID-19).

RESULT: Fully vaccination rates were lower among Black and African American individuals with ADRD/MCI compared to non-Hispanic Whites (82.7% vs 88.2%). Higher education and income were associated with higher vaccination rates in individuals with ADRD/MCI. However, at 6 months post vaccination, individuals with ADRD/MCI experienced significant waning of vaccine effectiveness compared to those without ADRD/MCI, with effectiveness decreasing from 96.7% two weeks after fully vaccination to 76.4% after 6 months, and 54.2% after 1 year and 6 months. Greater waning of vaccine effectiveness was observed in individuals aged over 65 years old, and multiple chronic conditions (e.g.

, COPD: 69.6%; Cancer: 73.5%; Stroke: 71.1%; Hypertension: 74.6%; Diabetes: 78.9%; Depression: 73.9%; Anxiety: 74.1%) at 6 months after fully vaccination compared to healthy adults.

CONCLUSION: This study advances understanding of COVID-19 vaccination effectiveness among individuals with ADRD/MCI and highlights the influence of chronic conditions on vaccine effectiveness. Efforts to promote vaccination boosters tailored to the currently circulating virus are essential for vulnerable people. Public health efforts can be focused on increasing booster shots among individuals with ADRD/MCI to ensure equitable and effective coverage.},
}

Humans
*COVID-19/prevention & control/epidemiology
Cross-Sectional Studies
Retrospective Studies
Male
Female
Aged
*COVID-19 Vaccines
*Public Health
Middle Aged
SARS-CoV-2
*Vaccination/statistics & numerical data
Aged, 80 and over
United States/epidemiology
*Vaccine Efficacy
Alzheimer Disease/epidemiology

@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 {pmid41427440,
year = {2025},
author = {Adler, BL and Rebman, AW and Chung, T and Miller, JB and Keshtkarjahromi, M and Yang, T and Savigamin, C and Azola, A and Rowe, PC and Aucott, JN},
title = {Autonomic Symptoms in Post-Treatment Lyme Disease: Insights From the COMPASS-31 and the 10-Minute Active Stand Test.},
journal = {Mayo Clinic proceedings. Innovations, quality & outcomes},
volume = {9},
number = {6},
pages = {100674},
pmid = {41427440},
issn = {2542-4548},
abstract = {OBJECTIVE: To determine the prevalence of autonomic symptoms in post-treatment Lyme disease (PTLD) and identify clinical factors that associate with abnormal hemodynamics on the 10-minute active stand test.

PATIENTS AND METHODS: We administered the Composite Autonomic Symptom Score-31 survey to 37 patients with PTLD and compared them with a cohort of patients with postural orthostatic tachycardia syndrome (POTS) without a known history of Lyme disease. We also report the 10-minute active stand test performed in 210 patients with PTLD recruited from July 1, 2016 through October 31, 2024.

RESULTS: Patients with PTLD had higher total Composite Autonomic Symptom Survey 31 scores than healthy controls and reported similar vasomotor, urinary, and pupillomotor symptom burden as patients with POTS. On the 10-minute active stand test, 9 of the 210 (4.29%) patients with PTLD had orthostatic tachycardia. Although the prevalence of orthostatic tachycardia in patients was not significantly different from that of healthy controls, those with orthostatic tachycardia were more likely to be earlier in their disease course and had higher rates of steroid use (P=.009) and antibiotic exposure (P=.007) after Lyme disease.

CONCLUSION: Autonomic symptoms are common in PTLD. The 10-minute active stand test identified a subgroup of patients with orthostatic tachycardia that associated with distinct clinical features of Lyme disease.},
}

@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 {pmid41426470,
year = {2023},
author = {Castellanos, PL and Satashia, P and Punj, M and Castillo, PR and Colaco, BM and Dredla, BK and Festic, E and Kaplan, J and Ruoff, CM and Speicher, LL and Walsh, KL and Werninck, N and Yin, M and Burger, CD and Arunthari, V and Cheung, J},
title = {Assessment of sleep quality and sleep disordered breathing among post-hospitalized patients with COVID-19.},
journal = {Frontiers in sleep},
volume = {2},
number = {},
pages = {1214036},
pmid = {41426470},
issn = {2813-2890},
abstract = {BACKGROUND AND OBJECTIVES: We conducted a cross-sectional study to identify the presence of sleep disturbance and sleep disordered breathing in post-hospitalized patients with COVID-19 compared to a cohort of patients with no prior COVID-19 infection.

METHODS: Patients who were discharged from Mayo Clinic after hospitalization for COVID-19 and who had no existing diagnosis of sleep apnea or other sleep disorders were recruited for this study as cases. Patients who never had COVID-19 infection, nor any existing diagnosis of sleep apnea or other sleep disorders, were recruited from outpatient clinics as controls. Participants completed Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Fatigue Severity Scale questionnaires, as well as a home sleep apnea test.

RESULTS: Forty-seven COVID-19 cases and 46 controls completed questionnaires. Cases were significantly older, with a median age of 56.0 vs. controls (50.5) and were found to have slightly worse sleep quality, a higher degree of daytime sleepiness, and a slightly higher degree of fatigue. In terms of sleep disordered breathing, 39 cases and 40 controls completed the home sleep apnea test. Obstructive sleep apnea, defined by an AHI score of 5 or higher, was found in a remarkable 97.4% of cases vs. 72.5% in controls. Severity of OSA also trended higher in the case group. However, the difference in AHI was not significant after adjusting for age and BMI.

CONCLUSION: Patients who were hospitalized with COVID-19 showed a very high prevalence of OSA. In addition, they had a slightly higher degree of sleep disturbance, daytime sleepiness, and fatigue when compared to controls. Our results suggest that sleep medicine assessment in patients who had COVID-19 requiring hospitalization is warranted.},
}

@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 2,819 referrals, 81% (n = 2,287) 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},
doi = {10.1073/pnas.2509118122},
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},
doi = {10.1093/ije/dyaf196},
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 = {},
doi = {10.1136/bmjment-2025-301969},
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 {pmid41403426,
year = {2025},
author = {Baldwin, MM and Daynes, E and Karsanji, U and McAuley, HJC and Bishop, NC and Bolton, CE and Man, WD and Vogiatzis, I and Chalmers, JD and Ho, LP and Horsley, A and Marks, M and Poinasamy, K and Raman, B and Leavy, OC and Richardson, M and Elneima, O and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Houchen-Wolloff, L and Greening, NJ and Harrison, EM and Docherty, AB and Lone, NI and Quint, JK and Wain, LV and Brightling, CE and Evans, RA and Singh, SJ},
title = {The safety, physiological response and repeatability of the incremental shuttle walk test in survivors of COVID-19.},
journal = {ERJ open research},
volume = {11},
number = {6},
pages = {},
pmid = {41403426},
issn = {2312-0541},
abstract = {BACKGROUND: The incremental shuttle walk test (ISWT) may be a valuable tool for measuring exercise tolerance in patients after a hospital admission with COVID-19. However, the safety, physiological response and repeatability of the ISWT are unknown in this cohort. The present study aimed to explore the properties of this test using the Post-Hospital COVID-19 (PHOSP-COVID) study.

METHODS: Participants performed two ISWTs, with a 30-min rest between tests, at 5 and 12 months post-hospital discharge for COVID-19. Heart rate and fingertip peripheral oxygen saturation were recorded pre- and post-test. Reasons for test termination were noted.

RESULTS: 1593 individuals (median (interquartile range) age 58 (50-66) years and body mass index 31.2 (27.6-35.8) kg·m[-] [2]; 967 (60.7%) males) performed an ISWT; two tests were performed by 1034 and 390 participants at the 5- and 12-month visit, respectively. At 5 months post-discharge, six patients (0.4%) had an adverse event and the most common reason contributing to test termination was breathlessness (826 (54.2%) participants). 336/1470 (22.9%) participants experienced exertional desaturation. Distance walked was greater in the second ISWT compared to the first ISWT at 5 and 12 months post-discharge (mean±sd difference: 5 months: 19±94 m; 12 months: 11±80 m; p<0.05), with an intraclass correlation coefficient estimate of 0.96 (95% CI 0.95-0.97) at 5 months and 0.97 (95% CI 0.96-0.97) at 12 months.

CONCLUSIONS: The ISWT appeared to be safe in this large cohort, supporting use of this field walking test for this population in clinical and research settings. A familiarisation test is recommended, with further study needed to determine the number of familiarisation tests required to achieve acceptable within-day repeatability.},
}

@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)/ ; },
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.},
}

@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},
}

@article {pmid41396732,
year = {2025},
author = {Asghar, AF and Enderle, J and Salazar, JH and Esani, M},
title = {Predictors of post-acute sequelae of coronavirus disease 2019 and long COVID in adults and children: a retrospective cohort study using us electronic health record data.},
journal = {Journal of public health (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/pubmed/fdaf157},
pmid = {41396732},
issn = {1741-3850},
abstract = {OBJECTIVE: This study examined the incidence and predictors of post-acute sequelae of COVID-19 (PASC) and Long COVID in adults and children with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Associations assessed included demographic factors, comorbidities, lab markers, and patient clinical complications.

METHOD: A retrospective cohort of 13,940 patients with confirmed SARS-CoV-2 infection (7836 adults and 6104 children) from the Optum® COVID-19 Electronic Health Record dataset was analyzed (1 June 2020-30 June 2021). PASC was defined as symptoms lasting <3 months postinfection and Long COVID as symptoms ≥3 months. Inclusion criteria were patients of all ages with a confirmed SARS-CoV-2 infection. Excluded from the study were patients in the Texas Department of Criminal Justice system and patients with active HIV, malignancy, or respiratory viral/bacterial infection. Statistical analyses (chi-square, Mann-Whitney U, multivariable logistic regression) were performed using Microsoft Excel and IBM Statistical Package for the Social Sciences statistics V.25.

RESULTS: Symptoms consistent with PASC were reported by 21.5% of adult patients, with 8.8% reporting Long COVID; 10.5% of pediatric patients reported PASC, with 9% reporting Long COVID (P < .05). In adults, predictors of PASC included age ≥54, female sex, non-Caucasian race, smoking, obesity, pneumonia, and multiple comorbidities; higher red blood cell count was protective. Predictors of Long COVID in adults was associated with female sex, obesity, and heart disease. In children, predictors of PASC included female sex and comorbidities. Younger age (≤10 years) was a significant predictor of Long COVID in children.

Protocols that include targeted follow-up and early intervention are needed for post-COVID conditions in high-risk individuals across age groups. Integrating predictive markers into routine care could enhance preparedness and resilience against future waves of post-viral syndromes.},
}

@article {pmid41396195,
year = {2025},
author = {Sharma, V and Epstein, R and Arora, MK and Edinger, T and Dahlquist, M and Flessner, C and McCullough, JM and Ghimire, U and Smith, LU and Reina Ortiz, M},
title = {Academic-Nonprofit Partnership for Public Health: Document Analysis and Systematization of the Implementation of a Multijurisdictional Long COVID Surveillance Platform.},
journal = {Journal of public health management and practice : JPHMP},
volume = {},
number = {},
pages = {},
pmid = {41396195},
issn = {1550-5022},
abstract = {CONTEXT: Health information exchanges (HIEs) are generally underutilized as data sources for public health surveillance, potentially decreasing the ability of public health practitioners to leverage the rich, real-time, clinical, and public health data therewith contained.

OBJECTIVES: To systematize the process of implementing an academic-nonprofit partnership (ANPP) designed to leverage multijurisdictional HIE data for public health surveillance of Long COVID by Systematizing the ANPP's. Implementation, with a focus on its operational strengths, opportunities, challenges, and strategies for its sustained growth.

DESIGN: Document review and analysis informed by the Centers for Disease Control and Prevention's Surveillance System Evaluation framework. We employed a systematic approach to the collection and interpretation of 5 types of documents to describe the experience of implementing a multistakeholder, multijurisdictional, HIE-based ANPP for public health surveillance from 2022 to 2025.

SETTING: Multijurisdictional settings in the US.

PARTICIPANTS: The ANPP and its constituent organizations.

INTERVENTION: Implementation of the ANPP.

MAIN OUTCOME MEASURE: Identification of critical lessons learned including key partnership elements, encountered challenges, surveillance framework application, and strategies for implementing a multistakeholder, multijurisdictional ANPP for public health surveillance.

RESULTS: A participatory, iterative approach was used to engage stakeholders on ANPP implementation. Foundational strengths included complementary partner expertise and robust data environments, which created unique opportunities for comprehensive Long COVID surveillance. Challenges involved navigating varied institutional, legal, and regulatory requirements, complex data permission structures, and coordinating teams across different time zones. Key lessons learned highlighted that extensive initial investment in legal frameworks, data environments, and communication protocols, though time-consuming, significantly improves surveillance capabilities. Strategies to ensure success included replacing large meetings with focused working groups, fostering frequent communication, and implementing rigorous inter-team data quality control.

CONCLUSION: Implementing multistakeholder, multijurisdictional, HIE-based surveillance necessitates substantial upfront investment. Continuous refinement and strategic efforts are vital for overcoming operational complexities and maximizing HIE potential for robust public health surveillance.},
}

@article {pmid41395800,
year = {2025},
author = {Evans, CR and Echols, MR and Martin, D and Taylor, HA and Washington, JA and Gbinigie, O and Gaglioti, AH and Wright, W and Hovmand, P},
title = {Leveraging Community-Based System Dynamics to Understand Long Covid Disparities in African American Communities: A Model for Health Equity Research.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70516},
doi = {10.1111/hex.70516},
pmid = {41395800},
issn = {1369-7625},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Black or African American ; *COVID-19/ethnology ; *Health Equity ; *Health Status Disparities ; Female ; Male ; *Community Participation ; SARS-CoV-2 ; *Healthcare Disparities ; White ; },
abstract = {BACKGROUND: Long Covid disproportionately affects African American communities, exacerbating pre-existing health disparities and systemic barriers to care. Conventional public health interventions often fail to address the complex systemic issues at play due to a lack of grounding in community-certified knowledge about the broader societal context that produces the disparities and in which the interventions must operate. New methods are needed to elicit community perspectives on living with long Covid.

METHODS: This study employed Community-Based System Dynamics (CBSD) workshops, conducted in hybrid formats (online and in-person), to engage African American communities impacted by long Covid. Participants included affected individuals, healthcare professionals and systems researchers.

RESULTS: The workshops yielded system dynamics causal loop diagrams that illustrate the multifaceted societal context and impact of long Covid. Community-driven insights led to the identification of targeted interventions and informed a comprehensive action plan designed to address specific health system barriers and enhance community resilience.

CONCLUSIONS: CBSD workshops proved effective in fostering significant community engagement and empowerment, presenting a replicable model for gaining a deeper understanding of the socio-cultural context that underlies complex health disparities. These findings suggest that incorporating community-sourced societal context knowledge and system dynamics modelling and analysis can substantially enhance public health strategies for managing long Covid.

People with lived experience of long Covid were actively involved throughout all phases of this study. Participants contributed to the design and facilitation of Community-Based System Dynamics (CBSD) workshops, helped construct and refine causal loop diagrams based on their experiences, and generated action ideas for future interventions. Their insights shaped both the structure and content of the system models and directly informed the interpretation of results. Several participants also reviewed and provided feedback on early drafts of the manuscript to ensure the findings reflected their perspectives and priorities.},
}

Humans
*Black or African American
*COVID-19/ethnology
*Health Equity
*Health Status Disparities
Female
Male
*Community Participation
SARS-CoV-2
*Healthcare Disparities
White

@article {pmid41394882,
year = {2025},
author = {Padilla-Blanco, M and García-García, T and Grigas, J and López-Ayllón, BD and Garrido, JJ and Oliva, MA and Montoya, M},
title = {Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1726698},
pmid = {41394882},
issn = {1664-3224},
mesh = {Humans ; *SARS-CoV-2/immunology/genetics ; *COVID-19/immunology/virology ; Host-Pathogen Interactions/immunology ; Interferon Type I/immunology/metabolism ; Animals ; *Viral Regulatory and Accessory Proteins/immunology/genetics/metabolism ; Viral Proteins/immunology ; },
abstract = {SARS-CoV-2 accessory proteins (APs), particularly ORF3a and ORF9b, have emerged as key modulators of host-pathogen interaction and potential contributors to long COVID. Of the 13 predicted APs, only nine are expressed during infection - termed Infection-related APs - while the remaining are classified as Putative APs. Despite this distinction, extensive gene overlap among APs underscores the remarkable adaptability of SARS-CoV-2 viral genome. This review delves into the diverse roles of the original Wuhan APs and their Omicron counterparts in shaping host immunity, with an emphasis on their ability to suppress type I interferon (IFN-I) signalling, modulate cellular metabolism, and trigger inflammatory/apoptotic pathways. By integrating immunopathological insights with evolutionary dynamics and structural perspectives, this review provides a comprehensive understanding of the mechanism underlying Omicron's reduced pathogenicity and highlights promising, yet unexplored, therapeutic targets within the SARS-CoV-2 accessory proteome.},
}

Humans
*SARS-CoV-2/immunology/genetics
*COVID-19/immunology/virology
Host-Pathogen Interactions/immunology
Interferon Type I/immunology/metabolism
Animals
*Viral Regulatory and Accessory Proteins/immunology/genetics/metabolism
Viral Proteins/immunology

@article {pmid41394849,
year = {2025},
author = {Gabig-Cimińska, M},
title = {Dysregulated TFEB-autophagy-lysosome pathway links acute COVID-19 immunopathology to Long COVID sequelae.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1708364},
pmid = {41394849},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/pathology/complications ; *Lysosomes/immunology/metabolism ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/immunology ; *Autophagy/immunology ; *SARS-CoV-2/immunology ; Animals ; Signal Transduction/immunology ; Immunity, Innate ; },
abstract = {SARS-CoV-2 disrupts cellular homeostasis, including the autophagy-lysosome pathway (ALP), a critical component of innate immunity and viral clearance. By subverting autophagy, SARS-CoV-2 proteins such as ORF3a, ORF7a, and NSP6 inhibit autophagosome-lysosome (APG-L) fusion, generating "incomplete autophagy" that permits viral persistence and drives hyperinflammation. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, has emerged as a central player in the host response to coronavirus infection. TFEB orchestrates the expression of genes required for lysosomal function and autophagic flux while also shaping immune processes, including cytokine production, interferon-stimulated gene expression, and inflammasome clearance. This mini review synthesizes current knowledge on the TFEB-ALP axis in COVID-19 pathogenesis, highlighting its influence on acute immunopathology and its potential contribution to post-acute sequelae (Long COVID). Restoring TFEB activity and autophagic flux may counteract SARS-CoV-2 evasion strategies and restrain aberrant inflammatory responses. Harnessing the TFEB-autophagy pathway as a host-directed therapeutic strategy could help rebalance immune homeostasis, limit tissue damage during acute infection, and mitigate persistent inflammatory sequelae in Long COVID.},
}

Humans
*COVID-19/immunology/pathology/complications
*Lysosomes/immunology/metabolism
*Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/immunology
*Autophagy/immunology
*SARS-CoV-2/immunology
Animals
Signal Transduction/immunology
Immunity, Innate

@article {pmid41393125,
year = {2025},
author = {Halma, M and Varon, J},
title = {Restoring trust in vaccination: listening to patients and acknowledging Post-Acute COVID Vaccine Syndrome.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1688170},
pmid = {41393125},
issn = {2296-858X},
abstract = {The National Academies of Science, Engineering, and Medicine (NASEM) has defined Long COVID as "an infection-associated chronic condition (IACC) that occurs after SARS-CoV-2 infection 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." This definition puts the experience of the patient primary, where the decisive factor for diagnosis is a persistent health problem after COVID-19 infection. Ongoing work aims to characterize the biological signature of both Long COVID and Post-Acute COVID-19 Vaccination Syndrome (PACVS), clinicians and researchers are faced with heterogeneous diseases that are not easily captured by a single biomarker. Candidate biomarkers establish spike protein persistence, either through detection of full length spike, the S1 subunit of spike protein, or anti-spike protein antibody positivity. Additionally, to rule out viral reservoirs or active infection as an explanation, anti-nucleocapsid antibody, a hallmark of COVID-19 infection not present in the vaccine, should be negative. Other candidate biomarkers include detection of vaccine sequence mRNA, or sequence differentiation of viral from vaccinal spike through mass spectrometry. Despite candidate biomarkers, medicine is far from a definitive diagnostic test. Lack of diagnosis has created negative experiences for patients and strengthened vaccine hesitancy. An open acknowledgement of vaccine risks is vital to restoring trust in science and medicine and ensuring those injured have access to the care they need.},
}

@article {pmid41388982,
year = {2025},
author = {Leavesley, MR and Dugen-Williams, C and Dobel-Ober, D and Carson, A},
title = {PCE-CfD and Long Covid: An NHS Service Evaluation on the Benefits of Using Person-Centred Experiential Counselling for Depression With People With Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70517},
doi = {10.1111/hex.70517},
pmid = {41388982},
issn = {1369-7625},
mesh = {Humans ; *COVID-19/psychology/complications ; Female ; Male ; State Medicine ; Middle Aged ; *Depression/therapy/etiology ; *Counseling/methods ; Adult ; Anxiety/therapy ; Aged ; SARS-CoV-2 ; *Person-Centered Psychotherapy/methods ; United Kingdom ; Cohort Studies ; },
abstract = {BACKGROUND: Long Covid is a condition affecting multiple organ systems and the mental health of patients. To address this, two National Health Service (NHS) services in the West Midlands developed an integrated long-term conditions (LTCs) pathway, co-produced between a 'Post Covid' service and an NHS Talking Therapy service for anxiety and depression (TTAD). Eligible people with Long Covid were offered person-centred experiential counselling for depression (PCE-CfD) to help improve their mental health. Despite limited evidence for PCE-CfD in managing depression linked to LTCs, it was identified that a humanistic approach could help address the disrupted self-narratives that existed with this cohort of patients.

OBJECTIVE: This NHS service evaluation investigated outcomes from clients with Long Covid who received PCE-CfD, specifically the impact on reduced depression and anxiety symptoms, and improved social and occupational functioning. It analysed pre- and post-treatment client/patient self-reported data using routine outcome measures, including the PHQ-9, GAD-7 and WSAS.

METHODS: A non-experimental cohort design was used to analyse anonymised routinely collected secondary data. Data that met the inclusion criteria were extracted for treatment delivered between August 2022 and October 2024. Paired t-tests were used to examine whether there were significant improvements between pre- and post-treatment outcome measures.

RESULTS: For people with Long Covid that completed treatment (n = 31), three t-tests were completed showing a significant reduction from PCE-CfD treatment, in depression (p < 0.01), anxiety (p < 0.01) and social functioning (p < 0.05). Cohen's d values indicated a very large effect size for a treatment effect in the reduction of depression (d = 2.1) and anxiety symptoms (d = 1.2). Recovery rates were analysed, using the NHS Talking Therapy recovery rate calculation, which showed that 83.87% of the people with Long Covid who were treated reached 'recovery', a much higher rate than the 48% NHS England target.

CONCLUSION: This NHS service evaluation underscores the effectiveness of PCE-CfD in reducing symptoms of depression and anxiety, as well as improving social and occupational functioning. These improvements observed in routine outcome measures highlight the benefits of offering a humanistic approach to people with Long Covid. These small but significant findings offer valuable insights into future service delivery and research in managing mental health challenges associated with chronic health conditions.

This NHS service evaluation uses secondary data analysis, meaning PPIE did not take place in advance. However, PPIE discussions could arise when disseminating its findings that could lead to further research in this area.},
}

Humans
*COVID-19/psychology/complications
Female
Male
State Medicine
Middle Aged
*Depression/therapy/etiology
*Counseling/methods
Adult
Anxiety/therapy
Aged
SARS-CoV-2
*Person-Centered Psychotherapy/methods
United Kingdom
Cohort Studies

@article {pmid41388153,
year = {2025},
author = {Aid, M and Boero-Teyssier, V and McMahan, K and Dong, R and Doyle, M and Belabbaci, N and Borducchi, E and Collier, AY and Mullington, J and Barouch, DH},
title = {Long COVID involves activation of proinflammatory and immune exhaustion pathways.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {41388153},
issn = {1529-2916},
support = {INV-027406, INV-041469//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; CA260476//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.},
}

@article {pmid41384659,
year = {2025},
author = {Bessalah, S and Sinha, D and Yuan, X and Paul, S and Longet, S},
title = {[Long COVID: therapeutic challenges and opportunities in the face of persistent sequelae].},
journal = {Medecine sciences : M/S},
volume = {41},
number = {11},
pages = {869-876},
doi = {10.1051/medsci/2025185},
pmid = {41384659},
issn = {1958-5381},
mesh = {Humans ; *COVID-19/complications/therapy/epidemiology ; *SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Chronic Disease ; },
abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has not only led to a global health and economic crisis but also renewed attention to a clinical phenomenon of persistent symptoms after viral infection. This phenomenon is defined as long COVID or post-COVID-19 syndrome. Approximately one in eight patients experience persistent symptoms of varying intensity after the acute phase of the infection. This phenomenon, combined with the virus's high transmissibility and rapid mutation rate, poses a major public health challenge. This review examines various therapeutic approaches currently under consideration for treating long COVID, and explores future prospects in this field.},
}

Humans
*COVID-19/complications/therapy/epidemiology
*SARS-CoV-2/physiology
Post-Acute COVID-19 Syndrome
Pandemics
COVID-19 Drug Treatment
Antiviral Agents/therapeutic use
Chronic Disease

@article {pmid41384154,
year = {2025},
author = {Floridia, M and Weimer, LE and Forte, AL and Palange, P and Ciardi, MR and Rovere-Querini, P and Agostoni, P and Barisione, E and Zucco, S and Andreozzi, P and Bonfanti, P and Figliozzi, S and Tosato, M and Lacedonia, D and Loso, K and Gnerre, P and di Rosolini, MA and Toraldo, DM and Martino, GP and Vagheggini, G and Parati, G and Onder, G and , },
title = {Administration of antivirals, IL-6 inhibitors, monoclonal neutralizing antibodies and systemic corticosteroids in acute SARS-CoV-2 infection do not reduce the subsequent burden of Long-COVID symptoms.},
journal = {Le infezioni in medicina},
volume = {33},
number = {4},
pages = {391-403},
pmid = {41384154},
issn = {2532-8689},
abstract = {PURPOSE: Some studies have suggested that therapeutic interventions able to mitigate the acute phase of COVID-19 can also reduce the risk of Long-COVID and its severity, but the issue is still controversial.

METHODS: We examined in a national cohort of patients followed in Long-COVID centers the risk of persistent symptoms according to administration in acute COVID-19 of four drug classes: antivirals, IL-6 inhibitors, monoclonal neutralizing antibodies and systemic corticosteroids. Final risk estimates for 26 symptoms were expressed as adjusted odds ratios calculated in multivariable logistic regression models that included as covariates demographics, comorbidities, BMI, smoking, severity of acute disease, hospitalization, level of respiratory support, SARS-CoV-2 vaccination and treatments administered during acute infection.

RESULTS: The final population included 1534 adult patients (mean age 60.3 years, 67.0% hospitalised during acute COVID-19). Treatments administered during acute phase included systemic steroids (52.8%), antivirals (20.7%, mostly remdesivir), IL-6 inhibitors (9.4%) and neutralizing antibodies (3.9%). After a mean interval of 338 days from acute COVID-19, 1181 patients (77.0%) presented persisting symptoms. For the drug classes considered, some protective associations were found in univariate analyses, that were however not maintained adjusting for confounders in multivariate analyses. Systemic corticosteroids and IL-6 inhibitors showed some negative associations with isolated symptoms.

CONCLUSIONS: Some drug classes showed a protective effect that was however not confirmed in multivariable analyses, underlining the importance of adjusting for a comprehensive number of covariates. Clinicians should consider the possibility that systemic corticosteroids and IL-6 inhibitors administered during acute COVID-19 may prolong the persistence of particular symptoms.},
}

@article {pmid41383902,
year = {2023},
author = {Mendoza-Portillo, E and Aleman-Navarro, E and Prieto, GA and Rosenstein, Y and Lozano-Nuevo, JJ and Perez-Lopez, A},
title = {Neurological manifestations with jugular vein thrombosis linked to an inflammatory profile may be a sequela of long COVID.},
journal = {Neuroprotection (Chichester, England)},
volume = {1},
number = {2},
pages = {170-175},
pmid = {41383902},
issn = {2770-730X},
abstract = {More than 670 million cases of coronavirus disease 2019 (COVID-19) have been recorded worldwide in the 3 years since the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. About 45% of survivors of COVID-19 develop a syndrome known as long-term COVID, in which symptoms persist even months after the acute infection. About 76% of patients with long COVID experience neurological manifestations. Moreover, patients who have survived COVID-19 have an increased risk of cerebral venous thrombosis. This case report describes a 41-year-old woman who developed neurological manifestations associated with jugular vein thrombosis 24 h after administration of the Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine (AstraZeneca-Serum Institute of India). She had been infected with SARS-CoV-2 three months before vaccination. Although initially suspected to be a case of vaccine-induced immune thrombotic thrombocytopenia (VITT) in view of her recent vaccination, the patient did not have any hallmarks of VITT, such as thrombocytopenia, an increased d-dimer level, or antibodies against platelet factor-4. Moreover, the neurological manifestations were associated with a high concentration of inflammatory cytokines, including interleukin (IL)-6, IL-17A, and IL-21, and elevated neutrophil levels in cerebrospinal fluid, suggesting that inflammatory immune components had a role in the development of thrombotic events and pointing to an alternative diagnosis. In this case, the laboratory results indicated that the neurological manifestations associated with jugular vein thrombosis were not associated with VITT. Therefore, we propose that the thrombosis of the left jugular vein was a sequela of SARS-CoV-2 infection.},
}

@article {pmid41381625,
year = {2025},
author = {Lersritwimanmaen, P and Thonghem, A and Wongsrisakunkaew, W and Kositamongkol, C and Phisalprapa, P},
title = {Prevalence and impact of long COVID on health-related quality of life in previously hospitalized COVID-19 patients: a 2-year follow-up study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31598-7},
pmid = {41381625},
issn = {2045-2322},
abstract = {Long COVID is a major health concern, yet evidence from Southeast Asia remains limited. We evaluated the prevalence, predictors, and health-related quality of life (HRQoL) impact of long COVID among hospitalized adults in Thailand over two years. This single-center, ambidirectional cohort combined retrospective chart review with prospective follow-up. The cohort comprised 295 adults hospitalized for symptomatic COVID-19 between August and November 2021. Interviews occurred at three months, one year, and two years post-infection. Long-COVID prevalence was 49.8% at three months; among these, 64.4% reported persistent symptoms at one year, and 22% of the one-year symptomatic group had symptoms at two years. Common symptoms included breathlessness, fatigue, and memory disturbance. Logistic regression identified severe-critical acute illness as a risk factor (adjusted odds ratio [aOR] 2.06, 95% CI 1.23-3.46), while full vaccination was protective (aOR 0.48, 95% CI 0.25-0.90). Long COVID was associated with lower HRQoL across all EQ-5D-5L domains. Long COVID was frequent among hospitalized Thai patients, with symptoms persisting in a substantial proportion up to two years. Severity of acute COVID-19 and vaccination status predicted long COVID. Long COVID was linked to reduced HRQoL, underscoring the need for follow-up and further confirmation in larger, multicenter studies.},
}

@article {pmid41379943,
year = {2025},
author = {Irving, SA and Rowley, EAK and Chickery, S and Natarajan, K and Klein, NP and Grannis, SJ and Ong, TC and Ball, SW and DeSilva, MB and Dascomb, K and Naleway, AL and Stockwell, MS and Stephens, AB and Zerbo, O and Hansen, J and Block, L and Jacobson, KB and Dixon, BE and Rogerson, C and Duszynski, T and Barron, MA and Mayer, D and Chavez, C and Weber, ZA and Reese, SE and Essien, I and Sheffield, T and Bride, D and Arndorfer, J and Van Otterloo, J and Koppolu, P and Mak, J and Kautz, A and DeCuir, J and Wiegand, RE and Payne, AB and Link-Gelles, R},
title = {Effectiveness of 2024-2025 COVID-19 Vaccines in Children in the United States - VISION, August 29, 2024-September 2, 2025.},
journal = {MMWR. Morbidity and mortality weekly report},
volume = {74},
number = {40},
pages = {607-614},
doi = {10.15585/mmwr.mm7440a1},
pmid = {41379943},
issn = {1545-861X},
mesh = {Humans ; Adolescent ; Child, Preschool ; Child ; United States/epidemiology ; *COVID-19 Vaccines/administration & dosage/immunology ; *COVID-19/prevention & control/epidemiology ; Infant ; *Vaccine Efficacy/statistics & numerical data ; Case-Control Studies ; Male ; Female ; Emergency Service, Hospital/statistics & numerical data ; SARS-CoV-2 ; },
abstract = {During September 2023-August 2024, approximately 38,000 COVID-19-associated hospitalizations occurred among children and adolescents aged <18 years in the United States, a rate of approximately 53 per 100,000 children, ranging from 600 per 100,000 children aged <6 months to 21 per 100,000 children and adolescents aged 5-17 years. On June 27, 2024, the Advisory Committee on Immunization Practices recommended that all persons aged ≥6 months receive a 2024-2025 COVID-19 vaccine, which targeted Omicron JN.1 and JN.1-derived sublineages. Investigators used a test-negative case-control design to estimate vaccine effectiveness (VE) of 2024-2025 COVID-19 vaccines against COVID-19-associated emergency department or urgent care (ED/UC) visits during August 29, 2024-September 2, 2025, among immunocompetent children aged 9 months-4 years and children and adolescents aged 5-17 years in the CDC-funded Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network (VISION), a multisite electronic health record-based network in nine states. Among children aged 9 months-4 years, VE against COVID-19-associated ED/UC visits was estimated at 76% (95% CI = 58%-87%) during the first 7-179 days after vaccination. Among children and adolescents aged 5-17 years, VE against COVID-19-associated ED/UC visits was an estimated 56% (95% CI = 35%-70%) during the first 7-179 days after vaccination. These findings suggest that vaccination with a 2024-2025 COVID-19 vaccine dose provided children with additional protection against COVID-19-associated ED/UC encounters compared with no 2024-2025 dose.},
}

Humans
Adolescent
Child, Preschool
Child
United States/epidemiology
*COVID-19 Vaccines/administration & dosage/immunology
*COVID-19/prevention & control/epidemiology
Infant
*Vaccine Efficacy/statistics & numerical data
Case-Control Studies
Male
Female
Emergency Service, Hospital/statistics & numerical data
SARS-CoV-2

@article {pmid41379191,
year = {2025},
author = {La Scaléa, ACR and Uehara, SCDSA},
title = {Pain in Long COVID: A scoping review of clinical characteristics and patterns of manifestation.},
journal = {Revista latino-americana de enfermagem},
volume = {33},
number = {},
pages = {e4777},
doi = {10.1590/1518-8345.7836.4777},
pmid = {41379191},
issn = {1518-8345},
mesh = {Humans ; *COVID-19/complications ; Female ; *Pain/etiology/diagnosis/epidemiology ; Male ; Pain Measurement ; SARS-CoV-2 ; },
abstract = {to map the available scientific evidence on the clinical characteristics and patterns of pain manifestation (location, frequency, duration, intensity, and quality) in individuals with Long COVID. a scoping review of publications from March 2020 to June 2024, indexed across four databases. Study selection was conducted by two independent, blinded reviewers. Data were extracted using a standardized instrument and analyzed descriptively. nineteen studies were included, indicating that pain affects individuals across all age groups, with higher prevalence among women, primarily involving the head, neck, shoulder, lower back, and hip. Pain frequency ranged from daily to monthly episodes, with duration exceeding one year in some cases. Intensity varied from mild to severe, and pain characteristics were diverse, with descriptors including burning, pressure, colicky, and throbbing pain. the clinical characteristics and patterns of pain manifestation in Long COVID are diverse. However, there is a paucity of studies providing detailed analyses of pain features and the influence of individual variables. These findings should guide future research and clinical practice toward a more comprehensive and contextualized assessment of pain in Long COVID.},
}

Humans
*COVID-19/complications
Female
*Pain/etiology/diagnosis/epidemiology
Male
Pain Measurement
SARS-CoV-2

@article {pmid41377364,
year = {2025},
author = {Rizvi, GS and Ullah, R and Khalid, M and Talha, M and Waafira, A},
title = {Circadian rhythm disruption and melatonin dysregulation as overlooked drivers of immune imbalance and multiorgan failure in post-COVID syndrome: a call for chronotherapy-based interventions.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {12},
pages = {9069-9070},
pmid = {41377364},
issn = {2049-0801},
abstract = {Post-COVID syndrome (long COVID) is increasingly recognized as a state of chronic inflammation, immune imbalance, and multiorgan dysfunction. Emerging evidence highlights circadian rhythm disruption and melatonin dysregulation as overlooked drivers of persistent symptoms such as fatigue, cognitive impairment, and immune dysregulation. Reduced melatonin impairs cytokine suppression, antioxidant defense, and mitochondrial protection, fueling inflammation and oxidative stress. These disruptions, coupled with autoimmune responses targeting adrenergic and muscarinic receptors, exacerbate systemic pathology. Preliminary data suggest that melatonin supplementation and chronotherapy may restore circadian alignment, rebalance immunity, and mitigate disease progression, although robust large-scale trials remain limited. Integrating circadian science into therapeutic protocols may provide a novel avenue for improving long-term outcomes in post-COVID patients.},
}

@article {pmid41375862,
year = {2025},
author = {Alghamdi, F and Obotiba, AD and Meertens, R and Alshalawi, O and Mokbel, K and Strain, WD and Knapp, KM},
title = {Assessment of Bone Mineral Density, Total Body Composition and Joint Integrity in Long COVID: A 12-Month Longitudinal Feasibility Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
doi = {10.3390/jcm14238558},
pmid = {41375862},
issn = {2077-0383},
support = {a PhD scholarship from Qassim University, Saudi Arabia.//Qassim University/ ; },
abstract = {Background/Objectives: A subset of individuals develops persistent symptoms following SARS-CoV-2 infection, including musculoskeletal (MSK) manifestations, a condition known as long COVID (LC). Emerging hypotheses suggest that chronic low-grade inflammation in LC may impair bone metabolism and compromise joint health. However, empirical evidence is limited, and the impact of LC on MSK health, particularly bone and joint integrity, is poorly understood. To determine the influence of LC on MSK function, including bone health, body composition, and joint integrity. Methods: A 12-month longitudinal prospective cohort feasibility study was conducted involving 45 adults with LC and 40 well-recovered (WR) post-COVID-19 controls. Baseline and follow-up assessments included dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD) and total body composition (TBC), alongside ultrasound of the hand and knee joints to evaluate intra-articular changes. Results: The LC group had more fat in the gynoid, android, and leg regions at each assessment point compared to the controls (p < 0.01). LC showed a significantly lower knee synovial hypertrophy at the baseline, 13.3% compared to WR 45% (p = 0.001), and a marginal improvement in hand synovial hypertrophy, over 12 months, from a median of 2 (IQR 1;5) to 1 (IQR 0;3) (p = 0.012), as observed via MSK ultrasound. No notable differences were found between groups regarding BMD, either in the LC group compared to the control group or overtime. Conclusions: This cohort study of LC adults and controls found no evidence of rapid bone loss; however, adiposity and joint symptoms suggest the need for ongoing monitoring. Future research should focus on MSK markers, muscle function, advanced imaging, and improving MSK health.},
}

@article {pmid41373075,
year = {2025},
author = {Jornada Ben, Â and Varga, AN and de Bruijn, S and Dekker, WB and van den Wijngaard, CC and Verburg, AC and Hoogeboom, TJ and van der Wees, P and Ostelo, RWJG and Bosmans, JE and van Dongen, JM},
title = {A comparison of allied healthcare versus no allied healthcare on participation, fatigue, physical functioning and health-related quality of life for patients with persistent complaints after a COVID-19 infection.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2600139},
doi = {10.1080/07853890.2025.2600139},
pmid = {41373075},
issn = {1365-2060},
abstract = {OBJECTIVE: To assess the effectiveness of allied healthcare versus no allied healthcare.

MATERIALS AND METHODS: Data from the ParaCOV cohort (allied healthcare, n = 1,451) and the LongCOVID cohort (no allied healthcare/control, n = 1427) were analyzed. Average treatment effects (ATEs) between groups were estimated using Targeted Maximum Likelihood Estimation adjusted for age, sex, body mass index, smoking status, comorbidities, and effect outcomes' baseline values. A ≥ 10% between-group difference in improvement from baseline (BTGD) was considered clinically relevant for participation, fatigue, and physical functioning, and ≥0.062 for health-related quality of life.

RESULTS: Patients receiving allied healthcare were older (49.2 vs. 41.2 years), less often female (63.3% vs. 70.1%), had higher BMI (28.2 vs. 26.1), smoked less frequently (5.0% vs. 9.0%), had more comorbidities (49.2% vs. 41.9%), and lower baseline anxiety and depression scores compared to those not receiving allied healthcare. For participation, ATEs after 6 and 12 months were respectively -2.62 (95%CI: -4.39; -0.86) and -1.68 (95%CI: -4.81;1.45), with BTGDs of 4.7% and 1.8% favoring the control. For fatigue, ATEs were 1.72 (95%CI: -0.14; 3.58) and 0.97 (95%CI: -1.48; 3.41), with BTGDs of 6.5% and 3.7% favoring the control. For physical functioning, ATEs were 5.75 (95% CI: 4.42; 7.09) and 6.36 (95%CI: 4.84; 7.88), with BTGDs of 1.4% and 2.2% favoring allied healthcare. For health-related quality of life, ATEs were 0.017 (95%CI: -0.008; 0.0044) and 0.033 (95%CI: 0.011; 0.054).

CONCLUSIONS: Patients with persistent complaints after a COVID-19 infection showed significantly lower participation after 6 months, higher health-related quality of life after 12 months, and better physical functioning after 6 and 12 months of allied healthcare, however, BTGDs were not clinically relevant. Study limitations warrant cautious results interpretation.},
}

@article {pmid41372831,
year = {2025},
author = {Bigogo, G and Audi, A and Ogwel, B and Aol, GO and Ouma, A and Oduor, C and Omondi, D and Komo, T and Nasimiyu, C and Agogo, G and Lo, T and Herman-Roloff, A and Munyua, P and Munywoki, PK},
title = {Risk factors for long COVID among participants of a population-based study in urban and rural Kenya, 2021.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-025-25863-7},
pmid = {41372831},
issn = {1471-2458},
abstract = {BACKGROUND: Post-COVID-19 conditions (PCC) or Long COVID, will linger due to continued circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the burden and risk factors of PCC could guide development of management guidelines for affected persons.

METHODS: Using Population-Based Infectious Disease Surveillance platforms established in Nairobi and Siaya Counties in Kenya, we followed up participants previously infected with SARS-CoV-2 between 01/05/2020 and 30/09/2021 to evaluate the presence and risk factors for PCC. Interviews were conducted from 13/10/2021 to 22/11/2021 to elicit information on the presence of four primary outcome categories: (i) presence of respiratory symptoms, (ii) self-reported non-recovery after SARS-CoV-2 infection, (iii) psychological distress, and (iv) worsening disability. The latter two were evaluated for persons ≥ 18 years old. Risk factors assessed included participants' demographic and clinical characteristics. Logistic regression models were developed for each outcome adjusted for household-level clustering.

RESULTS: Characteristics of the 832 participants from both sites were as follows; 82.7% were < 50 years, 59.3% were female, 5/511 (1.0%) were vaccinated with ≥ 1 dose of COVID vaccine. For the outcomes, 174/832 (20.9%) had respiratory symptoms, 165/793 (20.8%) reported non-recovery following SARS-CoV-2 infection, 152/511 (29.7%) had psychological distress, while 112/511 (21.9%) had a worsening disability. Females had greater odds of reported non-recovery from COVID-19 illness than males, adjusted odds ratio (aOR) of 1.47 (95%CI, 1.01-2.13). Underlying medical conditions was a significant risk factor for all outcomes: for presence of respiratory symptoms, aOR = 1.82 (95% CI, 1.16-2.87), for reported non-recovery, aOR = 1.93 (95% CI, 1.24-3.02), for psychological distress aOR = 1.87 (95%CI, 1.17-2.99), while for worsening disability aOR = 2.58 (95% CI, 1.54-4.34). Other significant predictors included living in the Asembo site associated with psychological distress (aOR = 2.23; 95% CI, 1.42-3.53), worsening disability (aOR = 2.38; 95% CI, 1.43-3.97), and presence of respiratory illness (aOR = 2.44; 95% CI, 1.67-3.56).

CONCLUSION: PCC were found in approximately one-fifth to one-third of participants with the presence of underlying medical conditions being a common risk factor in all outcomes. Advocacy for the prioritization of interventions such as vaccination of persons with underlying medical conditions could consequently result in a reduction in the risk of PCC.},
}

@article {pmid41372813,
year = {2025},
author = {Whitcomb, LA and Berry, K and LaVergne, SM and Natter, N and Baxter, BA and Rao, S and Tipton, M and Gritsenko, MA and Weitz, KK and Gerbasi, V and Bramer, LM and Piehowski, PD and Webb, TL and Henao-Tamayo, M and Chicco, AJ and Dunn, J and Dutt, TS and Ryan, EP},
title = {Blood pro-thrombotic analytes and platelet activation are associated with post-acute sequelae of COVID-19.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-025-11824-3},
pmid = {41372813},
issn = {1471-2334},
abstract = {Post-Acute Sequelae of COVID-19 (PASC), or "long COVID," describes persistent symptoms following recovery from SARS-CoV-2 infection. Early identification of circulating biomarkers predictive of PASC is critical for prognosis and therapeutic development yet remains poorly defined. To address this gap, we conducted a longitudinal, multi-omics analysis of blood samples from COVID-19 patients (n = 75), stratified by acute disease severity and PASC status. We integrated targeted multiplex assays, untargeted proteomics (LC-MS), and whole blood flow cytometry to define immune and vascular signatures associated with PASC. We found that individuals who went on to develop PASC exhibited a distinct phenotypic signature between 1 and 35 days post-infection, such as significantly elevated plasma Factor-IX, Tissue factor, and tPA, which reflected hyperactivation of immunothrombotic pathways. Similarly, pathway enrichment analysis revealed ongoing neutrophil degranulation, platelet activation, and extracellular matrix remodeling-indicating unresolved inflammation and immunothrombosis which persisted beyond 77 days post-symptom onset. Unlike prior studies using single biomarkers or limited timepoints, our study offers a comprehensive longitudinal analysis combining proteomic and cellular data to define a durable immune-vascular signature specific to PASC. This integrative approach reveals insights into PASC pathogenesis and highlights candidate biomarkers with potential utility in early risk stratification. Our findings underscore the critical role of chronic immune and endothelial dysfunction in long COVID and point toward actionable targets for intervention. This investigation links biorepository human samples with clinical symptoms and lays the foundation for precision diagnostics and therapeutic strategies aimed at improving long-term outcomes in COVID-19 survivors (NCT04603677).},
}

@article {pmid41372563,
year = {2025},
author = {Humer, B and Berentschot, JC and van Helden-Meeuwsen, CG and Bek, LM and de Bie, M and Defesche, TM and Boly, CA and Drost, M and Hellemons, ME and Dik, WA and Versnel, MA},
title = {Exaggerated IFN-I Response in Long COVID PBMCs Following Exposure to Viral Mimics.},
journal = {Journal of clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10875-025-01969-w},
pmid = {41372563},
issn = {1573-2592},
abstract = {PURPOSE: Long COVID (LC) is a long-term debilitating disease of which the exact pathophysiology is unknown. A dysregulated immune response resulting in hyperresponsive immune cells is hypothesized as a key mechanism in the development of LC. Several studies suggest that acute infections can leave lasting epigenetic changes, which result in heightened immune reactivity. Upon stimulation, these primed immune cells may exhibit exaggerated responses. This form of epigenetic memory can contribute to altered immune dynamics, particularly in response to induction of type I Interferons (IFN-I) pathway activation using a viral mimic. Therefore, we investigated if LC patients exhibit a hyperresponsive response towards viral mimics in comparison with healthy controls (HC).

METHODS: PBMCs of two distinct LC cohorts, characterized by a different disease course and duration, were collected and transfected using Lyovec with the cGAS and RIG-I agonists G3-YSD and 3p-RNA followed by measurement of IFN-I bioactivity with a reporter cell line.

RESULTS: Transfection of PBMCs of LC patients with the cGAS and RIG-I agonists resulted in increased IFN-I bioactivity in comparison with HC. Unsupervised hierarchical clustering revealed two distinct clusters, each predominantly composed of either patients or HC. In addition, a moderate correlation between RIG-I stimulation with 3p-RNA and fatigue severity scores was found.

CONCLUSION: These data show a hyperresponsive phenotype of immune cells of LC patients upon stimulation with viral mimics. The current availability of biologicals and small molecule inhibitors that interfere with aberrant IFN-I pathway activation underscores the importance of pursuing future investigations into this phenomenon.},
}

@article {pmid41370476,
year = {2025},
author = {Szwarcwald, CL and Malta, DC and Almeida, WDS and Souza Júnior, PRB and Damacena, GN and Gomes, CS and Castilho, EA},
title = {Inequities in COVID-19 morbidity in Brazil: the influence of demographic and socioeconomic characteristics and preexisting health conditions.},
journal = {Revista brasileira de epidemiologia = Brazilian journal of epidemiology},
volume = {28},
number = {},
pages = {e250056},
doi = {10.1590/1980-549720250056},
pmid = {41370476},
issn = {1980-5497},
mesh = {Humans ; *COVID-19/epidemiology ; Brazil/epidemiology ; Female ; Male ; Adult ; Cross-Sectional Studies ; Middle Aged ; Socioeconomic Factors ; Young Adult ; Adolescent ; Sociodemographic Factors ; Aged ; Prevalence ; *Health Status Disparities ; },
abstract = {OBJECTIVE: To analyze COVID-19 morbidity according to sociodemographic characteristics and preexisting health conditions, based on data from a survey conducted in 2023 online called "ConVid-2 Behavior Survey".

METHODS: This was a cross-sectional epidemiological study using the Respondent-Driven Sampling (RDS) method. Prevalence estimates and 95% confidence intervals were calculated for five COVID-19-related indicators. Logistic regression models were applied to test the hypothesis of associations between outcomes and sociodemographic characteristics.

RESULTS: The sample included 3,805 individuals aged 18 years or older. Approximately 50% of participants had received four or more doses of the COVID-19 vaccine. The estimated prevalence of COVID-19 was 49.5%, with significant and increasing gradients by age and decreasing gradients by education level. Long COVID was identified in 32% of individuals with confirmed COVID-19, with the highest proportions among women (38.3%; OR=0.52; p=0.002), those with financial difficulties (38.9%; OR=1.68; p=0.02), and those with a chronic noncommunicable disease (36.3%; OR=1.58; p=0.03). The highest rate of hospitalization occurred among those with Long COVID (12.7%). Death of a household member due to COVID-19 was reported by 5.1% of participants.

CONCLUSION: The findings revealed major socioeconomic inequalities across all indicators related to COVID-19 morbidity. Older age, preexisting health conditions, and Long COVID contributed to greater disease severity and increased hospitalization. These findings are relevant to inform public policies aimed at supporting the diagnosis and management of COVID-19-related complications within the public health system.},
}

Humans
*COVID-19/epidemiology
Brazil/epidemiology
Female
Male
Adult
Cross-Sectional Studies
Middle Aged
Socioeconomic Factors
Young Adult
Adolescent
Sociodemographic Factors
Aged
Prevalence
*Health Status Disparities

@article {pmid41369621,
year = {2025},
author = {Keller, C and Mascarenhas, L and Reyes, JL and Duval, S and Benditt, DG},
title = {Association of Autonomic Dysfunction With Long COVID: Evaluation Using Quantitative Autonomic Testing.},
journal = {Journal of the American College of Cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacc.2025.09.1608},
pmid = {41369621},
issn = {1558-3597},
abstract = {BACKGROUND: Persistent symptoms (eg, heart palpitations, lightheadedness, fatigue) despite resolution of acute COVID-19 infection is termed "long COVID syndrome" or simply "long COVID." Long COVID is believed to be associated with autonomic dysfunction, but the nature and severity of any autonomic disturbances are not well understood.

OBJECTIVE: This study sought to compare autonomic function measures in patients with long COVID, control subjects, and individuals with pure autonomic failure.

METHODS: Patients referred for autonomic testing were classified into 3 groups: long COVID (acute COVID-19 infection ≥12 weeks before testing), control subjects (COVID-19 negative, normal autonomic tests), and pure autonomic failure (COVID-19 negative, abnormal autonomic testing). Heart rate and blood pressure were recorded during active standing, Valsalva maneuver, respiratory sinus arrhythmia, and tilt-table testing.

RESULTS: Compared with control subjects, patients with long COVID exhibited both a greater heart rate increase and blood pressure drop with active standing and tilt-table testing (all P < 0.05). They also had lower Valsalva ratios and respiratory sinus arrhythmia values than did control subjects (both P < 0.05). Compared with pure autonomic failure patients, patients with long COVID had a greater heart rate increase but a lower drop in blood pressure with active standing and tilt-table testing and lesser respiratory sinus arrhythmia values and Valsalva ratios (all P < 0.001). After age and sex adjustment, autonomic dysfunction measures in patients with long COVID were comparable with those in the pure autonomic failure group. Further, autonomic testing abnormalities were observed in patients referred up to 40 months after infection.

CONCLUSIONS: When adjusted for age and sex, patients with long COVID may demonstrate persistent autonomic dysfunction that is similar to patients with pure autonomic failure.},
}

@article {pmid41368891,
year = {2025},
author = {Pinero, S and Li, X and Zhang, J and Winter, M and Lee, SH and Nguyen, T and Liu, L and Li, J and Le, TD},
title = {Omics-based computational approaches for biomarker identification, prediction, and treatment of Long COVID.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/10408363.2025.2583083},
pmid = {41368891},
issn = {1549-781X},
abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), is a major global health problem, with cumulative estimates suggesting that around 400 million people worldwide have been affected. It is characterized by persistent or new symptoms such as fatigue, cognitive impairment, and breathlessness lasting beyond four weeks after acute infection. Diverse clinical manifestations, chronic course, and incompletely understood pathophysiology-including hypotheses involving viral persistence, immune dysregulation, autoimmunity, endothelial dysfunction, and metabolic reprogramming-impede the development of diagnostic criteria, biomarkers, and targeted therapies. We conducted a critical review of 101 Long COVID omics studies, focusing on the computational methods used and their methodological quality. Using standardized criteria, we evaluated study design, statistical rigor, reproducibility, and clinical relevance across genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multiomics integration, and mapped these findings onto regulatory and translational frameworks. Despite substantial methodological heterogeneity, convergent biological signals emerged. Genomic studies implicate risk loci in immune and cardiopulmonary pathways. Epigenomic analyses identify differentially methylated regions in immune and circadian genes. Transcriptomic studies reveal persistent dysregulation of innate immune and coagulation pathways, as well as reproducible molecular endotypes. Proteomic studies consistently show abnormalities in the complement cascade and coagulation, with a small panel of complement proteins showing highly reproducible changes across independent cohorts. Metabolomic studies demonstrate sustained mitochondrial dysfunction and altered cellular bioenergetics for up to two years after infection. Multiomics integration supports at least two major endotypes, characterized by predominant inflammatory versus metabolic dysregulation, and provides a basis for patient stratification and computational treatment discovery. Machine learning models frequently achieve high classification performance, but are rarely externally validated. Critical limitations restrict clinical translation. Most studies are underpowered relative to analytical complexity, use heterogeneous case definitions and controls, and report platform-specific signatures with limited overlap. External validation, preregistered analysis plans, and regulatory-aligned assay development are uncommon. To date, no regulatory-approved diagnostic assay or evidence-based therapeutic intervention has directly emerged from these computational findings. Future progress requires harmonized phenotyping protocols, adequately powered longitudinal cohorts with external validation, integration of spatial omics and explainable artificial intelligence, and early engagement with regulatory and health-technology assessment pathways. This review provides a critical assessment and a translational roadmap, outlining how methodologically robust computational omics can be advanced toward clinically actionable tools for Long COVID.},
}

@article {pmid41368314,
year = {2025},
author = {Mkhabela, K and Van Staden, M and Chetty, YY},
title = {The long-term effects of COVID-19 on oxygen carrying capacity in adults at the University of Limpopo, South Africa.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1636141},
pmid = {41368314},
issn = {2296-858X},
abstract = {BACKGROUND: Long-COVID is a condition characterized by persistent symptoms that last past the acute phase of COVID-19. The symptoms manifest from COVID-19 infection, and include shortness of breath, fatigue, and headaches. These symptoms could be caused by hypoxia and hypoxemia which may result from low haematocrit and hemoglobin. The SARS-CoV-2 virus causes destruction to the heme group of hemoglobin leading to haemolysis, which may lead to disrupted oxygen-carrying capacity.

AIM: The aim of the study was to investigate the long-term effects of COVID-19 on hemoglobin (Hb) and haematocrit (Hct) in adults.

METHODOLOGY: This was a case-control cross-sectional study that included a COVID-19 non-naive group (n = 28) and a COVID-19 naïve group (n = 196). Questionnaires were administered to participants, and blood levels of Hb and Hct were measured. Furthermore, a food frequency questionnaire (FFQ) was administered to determine the daily intake of iron, folic acid, and vitamin B12 to observe if the diet might have had an influence on Hb and Hct.

RESULTS: The results show a trend for a low Hct is common in females who had a history of a positive COVID-19 test, and the trend for a normal Hb is prominent across the study population. Results also show a statistically significant (p = 0.001; 95% CI -1.064 to 9.295) intake of vitamin B12 in COVID-19 non-naive males, who also showed to have the highest levels of Hb and Hct (mean of 45.86 g/dl and 15.57% respectively) as compared to other groups.

CONCLUSION: COVID-19 patients in this study experienced persistent symptoms, but most of the participants had no symptoms at the time the study was conducted. Diet might have had an impact on Hb and Hct in the COVID-19 non-naive male population, as it was observed that they had the highest nutrient consumption and the highest concentrations.},
}

@article {pmid41367392,
year = {2025},
author = {Parks, JK and Johnson, BD and Shea, MG and Kim, CH and Johnston, JI and Carlson, A and Schwartz, JC and Wheatley-Guy, CM},
title = {Interrogating pulmonary diffusing capacity in long COVID: insights from DLCO and DLNO testing.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1725263},
pmid = {41367392},
issn = {1664-042X},
abstract = {INTRODUCTION: The lingering respiratory effects of COVID-19, particularly in patients with Long COVID, remain poorly understood, prompting a comprehensive evaluation of lung function in this population.

METHODS: Simultaneous measurements of diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), chest computed tomography (CT), lung ultrasound and questionnaires were collected in 74 subjects. Participants were categorized into two groups: those that have no lingering symptoms (NS, n = 37) and those still struggling with symptoms after initial infection, the disease known as Long COVID (LC, n = 37).

RESULTS: DLCO and DLNO were significantly lower in the LC group compared to the NS group (LC vs. NS, DLCO: 25.94 ± 7.65 vs. 21.71 ± 6.35 mL/min/mmHg, p = 0.009; DLNO: 148.5 ± 35.6 vs. 126.6 ± 32.2 mL/min/mmHg, p = 0.006). Pulmonary capillary blood volume (Vc) was also significantly lower in the LC group (43.38 ± 13.87, 70.79 ± 17.77, p = 0.003; LC vs. NS, respectively). Alveolar volume (VA) is significantly lower in the LC group (LC vs. NS, 5.06 ± 1.17 vs. 5.95 ± 1.16, p = 0.004). There was no significant difference between groups for surface area of the lungs available for gas exchange by resistance to gas transfer across the alveolar-capillary membrane (DM) between groups (LC vs. NS, 208.63 ± 97.3, 223.0 ± 93.47 mL/min/mmHg, p = 0.54). These findings indicate that Vc is the driving factor of decreased DLCO. CT findings and lung ultrasound showed no differences between the two groups for lung fluid (p = 0.525; p = 0.298).

CONCLUSION: These findings suggest that a lack of volume available for perfusion could be problematic for these patients and as such requires further investigation for clinical management of these patients.},
}

@article {pmid41367065,
year = {2025},
author = {Kamo, R and Miyagami, T and Saita, M and Hara, N and Mine, Y and Nishina, T and Fukui, Y and Harada, Y and Niitsuma, M and Naito, T},
title = {Virtual Pet-Assisted Therapy to Alleviate Symptoms of Long COVID: A Prospective Pilot Interventional Study.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {31},
number = {},
pages = {e950105},
doi = {10.12659/MSM.950105},
pmid = {41367065},
issn = {1643-3750},
mesh = {Humans ; Female ; *COVID-19/therapy/complications/psychology ; Pilot Projects ; Middle Aged ; Male ; Prospective Studies ; Adult ; *Animal Assisted Therapy/methods ; SARS-CoV-2 ; Animals ; Dogs ; Aged ; Post-Acute COVID-19 Syndrome ; Fatigue/therapy ; },
abstract = {BACKGROUND Post-COVID-19 condition (long COVID) is characterized by persistent symptoms following acute infection. Given the limited efficacy of pharmacologic treatments, there is growing interest in complementary, non-contact interventions. Virtual pet-assisted therapy (VAT), a virtual reality-based adaptation of animal-assisted therapy, may offer a novel strategy for symptom management in this population. MATERIAL AND METHODS A prospective intervention was conducted in the long COVID clinic at Juntendo University Hospital between July and December 2023. Adult patients with long COVID engaged with a virtual dog for 10 minutes prior to their clinical consultation. Twelve symptoms considered potentially responsive to short-term intervention were self-rated on a 10-point scale before and after the session, with scores representing mean values. RESULTS Forty-two participants (median age: 46 years; 71.4% female) were included in the analysis. The mean total symptom score decreased by 7.2%, from 34.6 points before the intervention to 32.1 points after (P=0.004). Fatigue scores decreased by 9.5% (from 6.3 to 5.7, P=0.004), dyspnea decreased by 17% (from 2.3 to 1.9, P=0.038), memory impairment decreased by 13% (from 4.8 to 4.2, P=0.015), and tinnitus decreased by 22% (from 2.3 to 1.8, P=0.012). CONCLUSIONS VAT could be a feasible and well-tolerated intervention worth further investigation as a potential adjunct for alleviating key symptoms of long COVID, particularly those with psychological components. Although this preliminary study is limited by the lack of a control group, it serves as a pilot study that demonstrates the potential of VAT.},
}

Humans
Female
*COVID-19/therapy/complications/psychology
Pilot Projects
Middle Aged
Male
Prospective Studies
Adult
*Animal Assisted Therapy/methods
SARS-CoV-2
Animals
Dogs
Aged
Post-Acute COVID-19 Syndrome
Fatigue/therapy

@article {pmid41365308,
year = {2025},
author = {James-Pemberton, PH and Kohli, S and Twynham, J and Westlake, AC and Antill, A and Olkhov, RV and Shaw, AM},
title = {Mass-Standardised Differential Antibody Binding to a Spectrum of SARS-CoV-2 Variant Spike Proteins: Wuhan, Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.4/5, BA.2.75 and BA.2.12.1 Variants-Antibody Immunity Endotypes.},
journal = {Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imm.70083},
pmid = {41365308},
issn = {1365-2567},
support = {//Attomarker Ltd/ ; //Exeter University Alumni/ ; },
abstract = {A fully mass-standardised quantitative comparative analysis of the differential antibody binding to spike variant proteins to SARS-CoV-2 has been performed for the variants: Wuhan, Alpha, Beta, Gamma, Delta and the Omicron variants BA.1, BA.2.12.1, BA.2.75, BA.4 and BA.5. Evolution of immunity through five patient cohorts (n = 148 in total) was studied including pre-pandemic, first infection, first vaccine, second vaccine and triple-vaccinated cohorts. A population of immunity endotypes has been observed and is classified against a recovery antibody threshold, with concentrations below this threshold being regarded as a 'dropout': U(+) showing protection to all variants; U(±) with single, double, triple and further dropout endotypes; and U(-) with all variant concentrations being under the threshold. The U(+) incidence rises significantly following multiple rounds of vaccination reaching an (n = 41) incidence of 54% (95% CI 39%-68%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection. The U(+) epitopes are targeted preferentially to the S1 region. U(±), with at least one dropout, has an incidence of 42% (95% CI 28%-57%), an immunity gap. Further, a U(-) sub-cohort of the population up to 13% does not make antibodies above the threshold and may not have a sterilising serum leading to persistent virus and a risk of Long COVID.},
}

@article {pmid41362895,
year = {2025},
author = {Kamdem, OL and Guyot, J and Dupre, C and Gouttefarde, P and Vericel, MP and Fanget, M and Nguefeu Nkenfou, C and Hupin, D and Roche, F and Botelho-Nevers, E and Bongue, B},
title = {Management of patients with post Covid-19 condition in France: A qualitative study exploring nurses' contributions to care pathways.},
journal = {Journal of public health research},
volume = {14},
number = {4},
pages = {22799036251390963},
pmid = {41362895},
issn = {2279-9028},
abstract = {OBJECTIVE: To investigate the different contributions made by nurses in the management of patients with post covid-19 condition (PCC) within the French healthcare context.

METHODS: We conducted a qualitative study among healthcare professionals in France and enrolled 17 nurses from different care sectors, including private practice, hospitals, schools, and research settings. Semi-structured interviews were conducted between October 2022 and June 2023. The inclusion criteria were: "be a nursing professional" and "having taken care of a patient with PCC." A content thematic analysis was carried out using NVIVO software with advanced pattern recognition analysis, applying the French nursing competency framework to categorize findings.

RESULTS: Five main themes emerged: (i) the diversity of nurses' contributions and responsibilities, (ii) psychological support: an essential nursing contribution, (iii) screening and referral activities for PCC patients, (iv) care coordination and inter-professional collaboration responsibilities, and (v) therapeutic patient education and clinical research participation. Nurses demonstrated expanded competencies in PCC symptom recognition, adapted traditional tasks to meet novel patient needs, and integrated evolving Long Covid knowledge with existing chronic disease management expertise.

CONCLUSION: The results offer important perspectives for the organization of the healthcare system and for the nursing profession in the management of chronic diseases. An important aspect of our findings concerns the coordination of care pathways, which raises the issue of task delegation to nurses, particularly in a context of healthcare professional shortages.},
}

@article {pmid41362299,
year = {2026},
author = {Ballouz, T and Kerksieck, P and Haile, SR and Dressel, H and Hämmig, O and Bauer, GF and Fehr, JS and Puhan, MA and Menges, D},
title = {Work ability trajectories and sick leave in individuals with post COVID-19 condition: 3-year follow-up of a population-based cohort.},
journal = {The Lancet regional health. Europe},
volume = {61},
number = {},
pages = {101536},
pmid = {41362299},
issn = {2666-7762},
abstract = {BACKGROUND: Data on the longer-term impact of post COVID-19 condition (PCC) on work-related functioning is limited, despite evidence on the persistence of PCC for years after infection. This study aimed to describe changes in work ability and sick leave associated with PCC up to three years post-infection.

METHODS: We used data from 667 working-age individuals within a prospective population-based cohort following individuals infected with SARS-CoV-2 between August 2020 and January 2021. PCC was determined at 12 months and work ability was assessed biannually. The impact of SARS-CoV-2 on participants' physical and mental work performance and COVID-19 related sick leave were assessed at three years.

FINDINGS: Participants with protracted COVID-19 related symptoms at 12 months after infection reported persistently lower work ability scores than those without symptoms, with no evidence of a difference in change over time (-0.12 points per year, 95% CI -0.29 to 0.07). Compared to recovered individuals, work ability scores among those with moderate health impairment improved by +0.72 points per year (95% CI -0.04 to 1.46), while trends were similar among those with mild or severe impairment. A higher proportion of participants with PCC reported worsening in physical and mental performance at work than those without PCC. Among those with PCC, 11.5% (9/78) reported taking COVID-19 related sick leave for one month or more, in contrast to 4.0% (13/327) among those without PCC.

INTERPRETATION: The study highlights the prolonged impact of PCC on work-related functioning and underscores the need for targeted occupational, clinical and social measures for those affected.

FUNDING: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe.},
}

@article {pmid41362171,
year = {2025},
author = {Chen, J and Wu, Y and Zhang, Z and Shen, M and Zhou, Y and Zhang, H and Zhuang, Z and Wang, S and Wang, D and Xu, L and Lu, Y and Chen, S},
title = {Utilizing the DMN and DAN to study the effects of acupuncture on patients with cognitive impairment in long COVID: a pragmatic randomized controlled trial protocol.},
journal = {Complementary medicine research},
volume = {},
number = {},
pages = {1-19},
doi = {10.1159/000549822},
pmid = {41362171},
issn = {2504-2106},
abstract = {Background Cognitive impairment is one of the long COVID symptoms that many people experience after Coronavirus Disease 2019 (COVID-19). Many individuals report a decline in cognitive functions, such as reduced memory and brain fog. These symptoms not only directly affect the cognitive functions of the brain but also hinder daily living activities, thereby reducing the quality of life. Moreover, these symptoms are significant risk factors for long-term cognitive decline in the elderly and can have both short-term and long-term effects on brain function.Clinically, acupuncture is widely used to improve cognitive impairment in the elderly. Elucidating the brain network mechanisms underlying acupuncture therapy for Long COVID-related cognitive impairment represents an urgently needed research focus. In this study, we employed acupuncture as an intervention to mitigate cognitive decline in Long COVID patients and investigate the potential mechanisms by which acupuncture alleviates cognitive impairment. Methods In this randomized controlled trial, 60 eligible participants are planned to be recruited and randomly assigned in a 1:1 ratio to the acupuncture group and the health education group, which will then receive acupuncture treatment and health education.The acupuncture group will participate in treatment three times per week for a total of eight weeks. The health education group will receive health education once per week for a total of eight weeks.The primary assessment index was the Montreal Cognitive Assessment Scale (MoCA), and the secondary assessment indexes included Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Activity of Daily Living Scale (ADL), Auditory Verbal Learning Test - Huashan Version (AVLT-H) and resting-state functional magnetic resonance imaging (rs-fMRI) data. These assessment indicators were all tested in one week each before and after the intervention was implemented. Discussion This trial aims to investigate the therapeutic effects of acupuncture on cognitive impairment in patients with long COVID and to further explore the imaging mechanisms by which acupuncture alleviates cognitive dysfunction in these patients. Trial registration: Chinese Clinical Trial Registry (http://www,chictr,org.cn), Registration number: ChiCTR2400092961,Date of Reqistration: 2024-11-26.},
}

@article {pmid41361800,
year = {2025},
author = {Reeder, HT and Thaweethai, T and Foulkes, AS},
title = {Penalized regression with negative-unlabeled data: an approach to developing a Long COVID research index.},
journal = {BMC medical research methodology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12874-025-02737-5},
pmid = {41361800},
issn = {1471-2288},
support = {R01HL162373/HL/NHLBI NIH HHS/United States ; R01HL162373/HL/NHLBI NIH HHS/United States ; R01HL162373/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Moderate to severe Long COVID is estimated to impact as many as 10% of SARS-CoV-2 infected individuals, representing a chronic condition with a substantial public health burden. An expansive literature has identified over 200 persistent symptoms associated with a history of SARS-CoV-2 infection; yet, there remains to be a clear consensus on a syndrome definition. Long COVID thus represents a "negative-unlabeled" outcome where those without prior infection must be Long COVID "negative" but those with prior infection have unknown or "unlabeled" Long COVID status. Despite this lack of a gold standard definition or biomarker, developing and evaluating an approach to characterizing Long COVID is a critical first step in future studies of risk and resiliency factors, mechanisms of disease, and interventions for both treatment and prevention.

METHODS: We recently applied a strategy for defining a numeric Long COVID research index (LCRI) using Lasso-penalized logistic regression, leveraging information on history of SARS-CoV-2 infection as a pseudo-label. In the current manuscript we formalize and evaluate this approach in a simulation framework for the occurrence of infection, Long COVID onset, and symptomatology. We evaluate its performance selecting symptoms associated with Long COVID and distinguishing individuals with Long COVID, in the presence of symptom correlations and demographic confounders. We compare the LCRI method to a simpler index defined by counting Long COVID symptoms, and assess these methods in a reanalysis of data on participants enrolled in the Adult Cohort of the Researching COVID to Enhance Recovery (RECOVER) study.

RESULTS: Simulation results demonstrate that the Lasso-penalized LCRI methodology appropriately selects symptoms associated with Long COVID, and that the LCRI has high discriminatory power to distinguish Long COVID, outperforming symptom count. This performance was robust to correlation between symptoms, and weighting methods are shown to successfully address potential confounding by demographic characteristics. Analysis of RECOVER data showed the LCRI outperforming symptom count by misclassifying fewer uninfected individuals as having Long COVID.

CONCLUSIONS: As the LCRI is increasingly used to characterize LC in research settings, this paper represents an important step in understanding its operating characteristics and developing general methodology for settings with negative-unlabeled data.},
}

@article {pmid41361535,
year = {2025},
author = {Marshall, M},
title = {Long-COVID research just got a big funding boost: will it find new treatments?.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41361535},
issn = {1476-4687},
}

@article {pmid41360602,
year = {2025},
author = {De Matteis, S and Consonni, D and Espinosa, A and de Cid, R and Magriña, NB and Castaño-Vinyals, G and Karachaliou, M and Alba Hidalgo, MA and Papantoniou, K and Garcia, J and Kogevinas, M and Straif, K},
title = {Occupational determinants of Long COVID in the population-based COVICAT cohort.},
journal = {Occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/oemed-2025-110398},
pmid = {41360602},
issn = {1470-7926},
abstract = {OBJECTIVES: Occupational factors affect SARS-CoV-2 infection risk, but the occupational factors associated with Long COVID (LC) are unknown. We aimed to address this issue using individual data in a population-based cohort.

METHODS: In the prospective COVICAT study, 2020-2023, Catalonia, Spain, we examined the association between occupational determinants and LC. Among subjects with previous SARS-CoV-2 infection, those employed in the pandemic and with occupational information were analysed. Different metrics, including four job-exposure matrices, were used to evaluate individual occupational risk factors for LC (postinfection symptoms ≥3 months). Poisson models were used to estimate adjusted risk ratios (RRs) and 95% CIs.

RESULTS: Among 2054 workers (1308 women, 746 men) aged 40-69 years, 486 developed LC (23.7%). Workers in jobs at high COVID-19 risk according to all metrics including health/social care, education, retail, transport and security showed higher LC risk. The main drivers of increased risk were close contact with colleagues and the public (RR up to 1.50; 95% CI 1.18 to 1.91), no social distance at workplace (up to 1.46; 95% CI 1.16 to 1.84), rare or no use of facemask (1.41; 95% CI 1.09 to 1.83) and commute by public transport (1.58; 95% CI 1.20 to 2.08). Working on-site during the pandemic was also associated with a higher LC risk compared with teleworking (1.57; 95% CI 1.19 to 2.09). Individual non-occupational risk factors for LC included female sex, comorbidities, obesity, number and severity of acute infections; vaccination and older age were protective.

CONCLUSIONS: In a population-based cohort, several occupational factors increased LC risk. Focused preventive strategies are warranted to avoid the associated public health burden. LC should be recognised and compensated as an occupational disease.},
}

@article {pmid41359411,
year = {2025},
author = {Al-Oraibi, A and Martin, CA and Woolf, K and Nellums, LB and Tarrant, C and Pareek, M},
title = {Patterns of long COVID symptoms among healthcare workers in the UK and variations by sociodemographic, clinical and occupational factors: a cross-sectional analysis of a nationwide study (UK-REACH).},
journal = {Journal of the Royal Society of Medicine},
volume = {},
number = {},
pages = {1410768251389692},
doi = {10.1177/01410768251389692},
pmid = {41359411},
issn = {1758-1095},
abstract = {OBJECTIVES: This study aimed to examine symptom patterns between healthcare workers (HCWs) with and without long COVID, identify the most common long COVID symptom groups and investigate how these symptom profiles vary across different ethnic groups, demographic characteristics, clinical factors and occupational roles in UK HCWS.

DESIGN: We conducted a cross-sectional study using data from the United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH) cohort study. Data were collected electronically between October 2021 and October 2022.

SETTING: United Kingdom.

PARTICIPANTS: Individuals aged 16 years or older, residing in the UK, working as HCWs or ancillary workers in a healthcare setting and/or registered with one of seven major UK healthcare professional regulators.

MAIN OUTCOME MEASURES: Long COVID was defined as symptoms persisting for ⩾12 weeks following SARS-CoV-2 infection. Our primary outcome was the presence or absence of particular groups of long COVID symptoms. We collapsed 28 symptoms into seven groups: cardiopulmonary, gastrointestinal, musculoskeletal, neurocognitive/neurologic, upper respiratory tract, psychological/social and systemic.

RESULTS: Among 4033 HCWs with a history of COVID-19, those with long COVID (26.5%; 1067/4033) reported a higher prevalence of systemic, neurological and psychological symptoms compared with those without long COVID. Among those with long COVID, the most commonly reported symptom groups were neurocognitive/neurologic (63.4%), cardiopulmonary (40.0%) - highest among Asian HCWs at 45.6% - and systemic (54.6%), which particularly affected Black and Mixed ethnicities at 64.0% and 63.9%, respectively. In multivariable analyses, Asian HCWs had higher odds of experiencing cardiopulmonary symptoms (adjusted odds ratio (aOR): 1.62, 95% CI 1.04-2.51, p = 0.032), while female HCWs were more likely to experience gastrointestinal (aOR: 3.78, 95% CI 1.14-12.45, p = 0.029) and neurocognitive symptoms (aOR: 1.58, 95% CI 1.10-2.28, p = 0.014). Compared with those in medical roles, musculoskeletal symptoms were more commonly reported by those in nursing (aOR: 2.50, 95% CI 1.32-4.72, p = 0.005), allied health professional (aOR: 1.82, 95% CI 1.01-3.30, p = 0.048) and dental roles (aOR: 3.07, 95% CI 1.31-7.17, p = 0.010). Vaccination with two or three doses was protective against several symptom groups, including cardiopulmonary, musculoskeletal and neurocognitive symptoms.

CONCLUSIONS: Our findings are the first to reveal distinct patterns in long COVID symptoms among HCWs with significant variations by ethnicity, sex and occupational role. These findings emphasise the need for targeted support strategies and workplace adjustments that consider both occupation-specific risks and individual sociodemographic factors.},
}

@article {pmid41358013,
year = {2025},
author = {Buettikofer, T and Maher, A and Johnson, M and Hartono, S and Rainbird, V and Nickels, M and Bennett, M and Huang, HC and Gaughwin, P and Vandermeide, MA and Carlyle, R and Ho, W and Brady, M and Patterson, K and Morris, J and Mitchell, I and Paratz, J and Freene, N and Bissett, B},
title = {Safety and Physical Outcomes of a Novel Australian Multidisciplinary Long COVID Clinic That Incorporates Exercise: A Prospective Observational Study.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {7827-7838},
pmid = {41358013},
issn = {1178-2390},
abstract = {BACKGROUND: Exercise therapy remains somewhat controversial in those with Long COVID (symptoms lasting >3 months), due to concerns for safety and the potential for harm.

PURPOSE: This study describes the safety and physical outcomes of an Australian multidisciplinary Long COVID Recovery Clinic that incorporates personalised exercise prescription including respiratory and peripheral muscle strengthening, carefully monitored cardiovascular training and pacing of activity.

PATIENTS AND METHODS: Prospective observational study of adults (≥18 years) engaging with a single site Long COVID Recovery Clinic (March 2022 to June 2023). Clinic eligibility required symptoms >12 weeks which impaired activities of daily living. Safety was pre-defined as <10% of participants experiencing a minor adverse event, and no serious disability or death as a result of participation in exercise. Physical outcomes included Modified COVID-19 Yorkshire Rehabilitation Scale, changes in exercise capacity (6-minute-walk-test), inspiratory muscle strength (maximum inspiratory pressure), Timed-Up-and-Go and ten-metre-walk-test. Data analysis included repeated measures Multivariate Analysis of Variance (MANOVA) to explore assessment and reassessment measures collectively, and repeated measures t-test.

RESULTS: Of 207 consumers referred, (62% male, median age 45, range 18-84), 119 (57% of the total referred) enrolled to participate in the program. Of these, 72 (61%) completed the program, median participation duration 112 days (range 5-384). There were no adverse events as a result of participation in exercise. Consumers who completed the program showed improvement in Modified COVID-19 Yorkshire Rehabilitation Scale Other Symptoms (MD -1.5, p=0.003), Overall Health Score (MD1.3, p<0.001), Total Score (MD -6.5, p=0.02); maximum-inspiratory-pressure (MD 11.7 cmH2O, p=0.002); Timed-Up-and-Go (MD -1.0 sec, p<0.001); ten-metre-walk-test comfortable speed (MD 0.7 m/sec, p=0.006) and fast speed (MD 0.2 m/sec, p<0.001); and 6-minute-walk-test distance (MD 63.0 m, p<0.001).

CONCLUSION: This multidisciplinary therapy program that incorporates exercise was safe and associated with improvements in physical and functional outcomes for participants who completed the program.},
}

@article {pmid41357843,
year = {2025},
author = {Małujło-Balcerska, E and Bączek, K and Górski, W and Kumor-Kisielewska, A and Gwadera, Ł and Białas, AJ and Piotrowski, WJ},
title = {Peripheral Levels of Selected Biomarkers in Patients with Post-Sarcoidosis Chronic Fatigue Syndrome.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {16921-16930},
pmid = {41357843},
issn = {1178-7031},
abstract = {INTRODUCTION: Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and multiple symptoms such as cognitive impairment and muscle pain, often linked to immune-inflammatory dysfunction. Sarcoidosis, a granulomatous disease with systemic inflammation, commonly causes fatigue, even during remission. This study examined whether fatigue and depressive symptoms in sarcoidosis remission relate to residual inflammation or oxidative stress. Recent studies highlight parallels between post-infectious fatigue syndromes, including Long COVID, and sarcoidosis-related fatigue, emphasizing IL-6 mediated pathways. Theoretical frameworks of immune-metabolic interactions further support the hypothesis that residual inflammation drives persistent fatigue in remission.

MATERIALS AND METHODS: Seventy-one sarcoidosis patients were divided into three groups: remission with fatigue (RS/CFS, n=22), remission without fatigue (R/S, n=23), and active sarcoidosis (A/S, n=26). Fatigue was assessed with the Fatigue Assessment Scale (FAS), depressive symptoms with the Beck Depression Inventory (BDI), and quality of life with PHQ-9. Pulmonary function tests measured FEV1 and FVC. Serum biomarkers (hsCRP, IL-6, TNF-α, total antioxidant status, and 8-isoprostanes) were measured by ELISA.

RESULTS: RS/CFS and A/S groups showed significantly higher fatigue, and depressive scores compared to R/S (P <0.05). HsCRP and IL-6 levels were elevated in fatigued patients (RS/CFS and A/S) versus non-fatigued (R/S) (P <0.05). IL-6 correlated moderately with fatigue and depression scores (r =0.33). No significant differences were found in TNF-α or oxidative stress markers. Pulmonary function was slightly reduced in fatigued patients and weakly correlated with mental fatigue (r = -0.26).

CONCLUSION: Our data support a role for low-grade systemic inflammation, especially elevated hsCRP and IL-6, in fatigue and depressive symptoms during sarcoidosis remission. Further research integrating inflammatory, oxidative, metabolic, and neuroendocrine pathways is needed to elucidate fatigue pathogenesis and develop targeted interventions. IL-6 may represent a potential biomarker of fatigue in sarcoidosis. These findings highlight the importance of persistent low-grade inflammation and may guide the development of future therapeutic strategies.},
}

@article {pmid41357833,
year = {2025},
author = {Liu, LD and Duricka, DL},
title = {Case Report: Celiac plexus block improves gastrointestinal Long COVID symptoms.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1589809},
pmid = {41357833},
issn = {1662-4548},
abstract = {Lingering symptoms following SARS-CoV-2 infection, recognized as the clinical entity "Long COVID," are common. Gastrointestinal dysfunction during and after COVID have received little attention to date and remain largely unaddressed. We have previously shown that numerous symptoms of Long COVID excluding gastrointestinal symptoms improve or resolve following stellate ganglion blocks (SGB). Here, we are first to report successful treatment of persistent post-COVID epigastric pain and diarrhea in three patients using celiac plexus block, a procedure commonly used for visceral abdominal pain and implicating the autonomic nervous system in Long COVID-associated GI symptoms.},
}

@article {pmid41357333,
year = {2025},
author = {Wu, CY and Reynolds, WC and Abril, I and McManus, AJ and Brenner, C and González-Irizarry, G and Gutiérrez-Martínez, L and Sun, O and Rosand, J and Tanzi, RE and Arnold, SE and Guzmán-Vélez, E},
title = {Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial.},
journal = {EClinicalMedicine},
volume = {89},
number = {},
pages = {103633},
pmid = {41357333},
issn = {2589-5370},
abstract = {BACKGROUND: Long-COVID often involves cognitive difficulties, immune dysregulation, and mitochondrial dysfunction. Studies suggest nicotinamide adenine dinucleotide (NAD+) precursors like nicotinamide riboside (NR) may reduce inflammation and support mitochondrial and neurological function. This double-blind, placebo (PBO)-controlled clinical trial with a placebo lead-in phase evaluated the effects of NR (2000 mg/day) on NAD+ and changes in cognitive and long-COVID symptoms.

METHODS: This was a 24-week, double-blind, placebo-controlled trial at a single center in Boston, USA, between August 2021 and September 2023. 58 community-dwelling participants with long-COVID were randomized 2:1 to the NR-NR group (NR for 20 weeks) or the PBO-NR group (PBO for 10 weeks, followed by NR for 10 weeks). The primary outcome was cognition, assessed using the Everyday Cognition scale (ECog), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and Trail Making Test-B (TMT-B). Secondary outcomes included the Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Pittsburgh Sleep Quality Index. We conducted a mixed model for repeated measures to compare groups, then post-hoc and unadjusted for multiplicity, combined both groups to explore changes from baseline after 10 weeks of NR. This trial was registered with ClinicalTrials.gov (NCT04809974) in 2021.

FINDINGS: 37 participants (64%) were assigned to NR-NR, and 21 participants (36%) to PBO-NR. There was a 32.4% and 51.4% dropout in the NR-NR group at 10 weeks and 20 weeks, respectively, vs. 14.3% dropout at each timepoint in the PBO-NR group. In the NR-NR group, NAD+ levels increased by 2.6- to 3.1-fold after 5-10 weeks of supplementation, respectively, and remained elevated at 20 weeks. In the PBO-NR group, NAD+ levels remained close to baseline (0.93- to 1.0-fold change, 95% CI: 0.5-1.4) during the initial 5 and 10 weeks of PBO. After switching to NR, levels rose to a 2.6-fold and 2.1-fold increase after 5 and 10 weeks of NR, respectively. No significant between-group differences were observed for cognitive outcomes (ECog, RBANS, TMT-B; p-values = 0.47-0.74). There were no significant differences in fatigue severity (p = 0.59), sleep quality p = 0.69), and symptoms of anxiety (p = 0.84) or depression (p = 0.20) between PBO and NR groups. In post-hoc exploratory analysis, examining within-group changes during 5 and 10 weeks of NR intake by grouping all participants during the first 10 weeks of the NR phase, there were significant differences from baseline after 10 weeks of NR in executive functioning, fatigue severity, sleep quality, and symptoms of depression (compared with no significant changes in TMT-B, FSS, PSQI, BAI, or BDI scores during the PBO phase). One serious adverse event was reported, deemed unrelated to the study drug or trial.

INTERPRETATION: In long-COVID, NR increased NAD+ within 5 weeks but did not significantly improve cognition, fatigue, sleep, or mood vs. PBO. Exploratory analyses suggested within-group benefits after 10 weeks of NR, supporting the need for larger trials.

FUNDING: This work was supported by Niagen Bioscience, the MGH McCance Center for Brain Health, Lavine Brain Health Innovation Fund, MGH ECOR CDI Physician-Scientist Development Award, and the Alzheimer's Association (grant no. AARGD-23-114103).},
}

@article {pmid41357034,
year = {2025},
author = {Baratta, JM and Jensen, KA and Cobb, C},
title = {Exploring the Effects of Pemivibart Monoclonal Antibody Infusion in Long COVID: A Case Series Offering Initial Clinical Insights.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {e96246},
pmid = {41357034},
issn = {2168-8184},
abstract = {Long COVID, or post-COVID conditions (PCC), affects a substantial proportion of adults and is characterized by persistent symptoms such as fatigue, postexertional malaise (PEM), cognitive dysfunction, and dysautonomia. At present, no Food and Drug Administration-approved therapies exist. Pemivibart (Pemgarda), a monoclonal antibody (mAb) authorized under Emergency Use Authorization (EUA) for preexposure prophylaxis in immunocompromised individuals, has not been studied for PCC but may theoretically facilitate clearance of viral antigens. We report three individuals with longstanding, debilitating PCC who received pemivibart infusion under EUA. Each experienced rapid symptomatic improvement, most notably in fatigue with PEM, dysautonomia, and cognitive dysfunction. One patient achieved resolution of her most limiting symptoms within a week and sustained functional recovery following repeat infusion. Another demonstrated significant gains across several symptom domains and was able to resume prior physical activities, although benefits waned after two to three weeks. A third with autoimmune comorbidities reported dramatic improvement in energy and cognition, and continued to feel well at six weeks. The rationale for this case series stems from emerging hypotheses that persistent viral antigens may contribute to the pathophysiology of Long COVID and that neutralizing antibodies could facilitate antigen clearance and symptom resolution. In the three cases, pemivibart infusion was temporally associated with rapid and meaningful improvement in fatigue associated with PEM, cognitive dysfunction, and dysautonomia, symptom clusters that often drive functional impairment in PCC. While the magnitude and duration of benefit varied among individuals, the consistent pattern of improvement supports further exploration of mAb therapy as a potential disease-modifying approach. These preliminary findings highlight the need for controlled, biomarker-guided studies to determine efficacy, durability, and patient subgroups most likely to respond. Pemivibart remains authorized only for preexposure prophylaxis in immunocompromised individuals and is not approved for the treatment of PCC.},
}

@article {pmid41354797,
year = {2025},
author = {Tanaka, S and Williams, S and Zhang, L and Yi, N and Garvey, WT and Cherrington, AL and Howell, CR},
title = {Persistent poverty, glycemic control and adverse COVID-19 outcomes: a retrospective study using real-world data.},
journal = {BMC public health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12889-025-25774-7},
pmid = {41354797},
issn = {1471-2458},
support = {U54MD008176//NIH NIMHD/ ; 931540//American Heart Association/ ; },
abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the profound impact of diabetes and neighborhood environments on health outcomes. Persistent poverty areas, characterized by long-standing economic deprivation, may contribute to increased risk for severe COVID-19 outcomes, particularly among individuals with poor glycemic control. This study investigated the associations between persistent poverty, longitudinal glycemic control by diabetes status, and adverse COVID-19 outcomes using real world data.

METHODS: We conducted a retrospective analysis using electronic health record (EHR) data from a large Academic health system. The sample included 3,681 adults diagnosed with COVID-19 between March 2020 and January 2021, with available HbA1c and neighborhood level data. Residence in census-tract level persistent poverty areas was categorized as yes vs. no while diabetes status and glycemic control were categorized into five groups based on history of diagnosis and HbA1c measured up to three years prior to infection. Bayesian multivariable logistic regression models assessed independent and multiplicative associations between living in a persistent poverty census tract, glycemic control by diabetes status, and adverse COVID-19 outcomes [e.g. hospitalization, intensive care unit (ICU) admission, and death during hospitalization], controlling for demographics and other social risk factors.

RESULTS: Among 3,681 patients (mean age 54 years; 60% female; 47% Black), 41.4% were hospitalized, 19.2% were admitted to the ICU, and 6.2% died. Overall, 18.0% resided in persistent poverty areas, 36.2% had diabetes [16.6% undiagnosed diabetes, and 11.1% poorly controlled T2DM]. Residing in persistent poverty areas was associated with an increased risk of hospitalization (OR 1.28, 95% CI: 1.02-1.61), ICU admission (OR 1.40, 95% CI: 1.08-1.80), and mortality (OR 1.50, 95% CI: 1.01-2.22). Patients with undiagnosed diabetes had an increased risk of hospitalization (OR 3.05, 95% CI 2.41-3.86) and mortality (OR 1.96, 95% CI: 1.30-2.97).

CONCLUSION: This study highlights that residing in a persistent poverty census tract as well as poor glycemic control independently contribute to COVID-19 outcomes. Ongoing management of glycemic control and early preventive strategies in persistent poverty areas may mitigate adverse outcomes in COVID-19 infection and subsequent sequalae like Long COVID.},
}

@article {pmid41354206,
year = {2025},
author = {Jiang, Z and Shan, T and Li, Y and Han, F and Feng, B and Zhen, X and Ni, H and Peng, J and Xu, M},
title = {Persistent Attenuation of Lymphocyte Subsets After Mass SARS-CoV-2 Infection.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108287},
doi = {10.1016/j.ijid.2025.108287},
pmid = {41354206},
issn = {1878-3511},
abstract = {OBJECTIVES: Growing evidence suggests that lymphocyte subsets are declined in COVID-19 patients, but it is unclear if these alterations persist after widespread exposure to SARS-CoV-2 or how long they last.

METHODS: We analyzed lymphocyte subset data from 40,537 patients across three phases: pre-COVID, mass infection, and post-COVID. The counts of lymphocyte subsets and CD4[+]/CD8[+] ratios were compared using Mann-Whitney U test or Kruskal-Wallis H test. Monthly post-exposure data were compared with pre-exposure data to assess the persistence of impact on lymphocyte subsets by SARS-CoV-2, and subgroup analyses were performed in patients with cardiovascular disease.

RESULTS: During mass infection, T cells, CD4[+]T cells, CD8[+]T cells, NK cells, and B cells dropped significantly. Even 20 months post-infection, CD8[+] T cells remained 9.9% below baseline. Baseline lymphocyte subsets differed significantly by sex and age. Immune recovery varied by age and sex, with older adults and males showing prolonged lymphopenia. In cardiovascular disease patients, T lymphocytes remained 72.9% below baseline for 20 months post-infection.

CONCLUSIONS: Our findings redefine SARS-CoV-2 infection as a condition of long-lasting immune compromise. The sustained subnormal lymphocytes-particularly in cardiovascular disease cohorts-highlight a key immunologic feature of long COVID and underscore the need for personalized care.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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