@article {pmid40934950,
year = {2025},
author = {Steenblock, C and Walther, R and Kok, Y and Mavberg, P and Yaman, M and Handgretinger, R and Castillo-Aleman, YM and Al Karam, M and Bornstein, SR},
title = {Single-Center Study of Therapeutic Apheresis in 24 Male Patients from the MENA Region: Reduction of Lipids, Inflammatory Markers, Autoantibodies, and Implications for Fatigue, Genetics, and Aging.},
journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2678-7739},
pmid = {40934950},
issn = {1439-4286},
abstract = {Cardiovascular and metabolic disorders, particularly diabetes and obesity, are highly prevalent in the Middle East and North Africa (MENA) region, exhibiting some of the highest global incidence rates. These conditions significantly increase the severity of infectious diseases, notably COVID-19, leading to a rise in long-COVID cases among affected individuals. Furthermore, the MENA region's extreme temperatures exacerbate cardiovascular issues by elevating heart rates and blood pressure, increasing dehydration and blood viscosity. Extracorporeal therapies, such as apheresis, effectively reduces plasma lipids and inflammatory markers. Furthermore, apheresis has shown promise in reducing autoantibodies associated to long-COVID. Our previous research indicated that apheresis alleviates symptoms in patients with long-COVID and chronic fatigue syndrome. In this study, we treated 24 male patients from the MENA region suffering from chronic fatigue and/or different metabolic diseases such as diabetes, dyslipidemia, or obesity, using double filtration plasmapheresis. Comprehensive plasma analyses were performed before and after apheresis to assess lipid profiles, inflammatory markers, and autoantibodies, revealing significant changes following the procedure. Genetic analyses on a subgroup of the patients showed no mutations in the LDLR, APOB, APOE, PCSK9, LIPA, and LDLRAP1 genes known to be associated with predispositions to monogenic lipid disorders. However, all patients in this subgroup demonstrated an intermediate to high likelihood that their elevated lipid levels have a polygenic basis. These findings suggest that implementing apheresis in the MENA region could significantly improve health outcomes and life expectancy for affected individuals.},
}

@article {pmid40934937,
year = {2025},
author = {Wilhelm, F and Cadamuro, J and Mink, S},
title = {Autoantibodies in long COVID: a systematic review.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00411-6},
pmid = {40934937},
issn = {1474-4457},
abstract = {Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers. This systematic review synthesises current evidence on the association between autoantibodies and long COVID, with the goal of evaluating their prognostic and diagnostic utility. Studies published in the PubMed and MEDLINE databases between Jan 1, 2020, and June 10, 2025, were considered. Study selection and quality assessment were done independently by two researchers. Of the 1113 publications screened, 44 studies met the inclusion criteria, with a total of 7571 participants, including 3372 individuals with long COVID. 31 (71%) studies reported an association between autoantibodies and long COVID; however, there was substantial heterogeneity in study design, type and timing of antibody measurements, and long COVID definitions. Several autoantibodies have been associated with long COVID occurrence, symptoms, and severity. Antinuclear antibodies, and autoantibodies targeting G protein-coupled receptors and chemokines, have emerged as potential biomarkers for aiding in the diagnosis, prognosis, and assessment of disease severity in long COVID. However, larger studies are needed to confirm the diagnostic and prognostic utility of these autoantibodies in the context of long COVID.},
}

@article {pmid40934019,
year = {2025},
author = {Gutiérrez-Martínez, L and Reynolds, WC and Abril, I and González-Irizarry, G and Ortiz-Acosta, P and Mullington, JM and Rosand, J and Tanzi, RE and Arnold, SE and Guzmán-Vélez, E},
title = {Sleep quality and efficiency in adults with post-acute sequelae of COVID-19.},
journal = {Sleep advances : a journal of the Sleep Research Society},
volume = {6},
number = {3},
pages = {zpaf051},
doi = {10.1093/sleepadvances/zpaf051},
pmid = {40934019},
issn = {2632-5012},
abstract = {STUDY OBJECTIVES: Sleep disruptions are associated with adverse mental and physical health outcomes. Individuals with post-acute sequelae of COVID-19 (PASC) commonly report worsened sleep. This study examined sleep quality and efficiency and their associations with neuropsychiatric symptoms and fatigue in non-hospitalized individuals with PASC.

METHODS: Sixty-one participants (73.8 percent female; - age = 45.4) who reported being infected with COVID-19 ≥ 2 months before enrollment, non-hospitalized, and experiencing ≥3 symptoms since infection were eligible. The Pittsburgh Sleep Quality Index was used to measure self-reported sleep quality, and the Fitbit Charge-4 to assess sleep efficiency. Participants completed the Beck Anxiety Index, Beck Depression Index, Post-Traumatic Stress Disorder-Checklist Civilian Version, and the Fatigue Severity Scale. We conducted multivariable linear regressions to examine associations controlling for age, sex, time since first COVID-19 infection, pre-COVID sleep disorders, and sleep aids.

RESULTS: Pittsburgh Sleep Quality Index scores were not associated with objective sleep efficiency. Nearly 97 percent of PASC participants reported poor sleep quality, 85 percent indicated that sleep difficulties interfered with their daily functioning, and 93.9 percent achieved optimal sleep efficiency. Higher Beck Depression Index scores were linked to worse sleep quality, while Beck Anxiety Index, Post-Traumatic Stress Disorder-Checklist Civilian Version, and Fatigue Severity Scale scores were not. However, Beck Anxiety Index and Fatigue Severity Scale scores were related to distinct Pittsburgh Sleep Quality Index components. None were associated with sleep efficiency.

CONCLUSION: Individuals with PASC experience significant sleep difficulties impacting daily functioning. Although they showed adequate sleep efficiency, most participants perceived their sleep as inefficient, which correlated with worse depressive symptoms. Therefore, sleep is a modifiable factor that could enhance the quality of life for patients with PASC.},
}

@article {pmid40933864,
year = {2025},
author = {Becker, JH and Li, J and Lin, JJ and Federman, A and Bagiella, E and Kale, MS and Fierer, D and Bartram, L and Wisnivesky, JP},
title = {Neurocognitive trajectories in long COVID: Evidence from longitudinal analyses.},
journal = {Brain, behavior, & immunity - health},
volume = {48},
number = {},
pages = {101093},
doi = {10.1016/j.bbih.2025.101093},
pmid = {40933864},
issn = {2666-3546},
abstract = {BACKGROUND: Patients frequently report symptoms of cognitive impairment or "brain fog" after acute COVID-19 infection, but the trajectory of these symptoms over time has yet to be determined. We assessed cognitive function over a 42-month period after acute SARS-CoV-2 infection and identified factors associated with the trajectory of cognitive function over this period.

METHODS: We analyzed data from participants in the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort study of adults followed after acute SARS-CoV-2 infection of any severity. Participants were identified from a list of all patients with COVID-19 who received care at an MSHS facility in New York, recruited beginning April 2020 and followed through January 2024. Cognition was assessed using well-validated in-person measures of attention, working memory, processing speed, executive functioning, language, and memory. We used linear mixed models to investigate the relationships between cognitive scores and time. We also assessed factors (including race, ethnicity, site of acute COVID-19 care, fatigue, depression, anxiety, body mass index, medical comorbidities, and COVID-19 vaccination) that may influence changes in cognitive scores over time.

FINDINGS: We analyzed data from 1553 participants (median age 53 years, 63 % female, 17 % Black, 21 % Hispanic). In adjusted analyses, scores from cognitive measures of attention, working memory, processing speed, executive functions, and verbal learning and memory improved progressively through 42 months post-COVID. However, despite the improvements, on average, measures of processing speed and executive functioning remained ≥1 standard deviation below the normative mean. Having a body mass index of <25 kg/m[2] was predictive of a greater improvement in cognitive scores.

INTERPRETATION: While cognitive impairment occurring after COVID-19 improved over time in most domains, processing speed and executive functioning remained below the normal range. The cognitive health burden of Long COVID is therefore significant and lasting. Future studies should examine interventions to support rapid recovery, as well as dynamic risk prediction models to determine factors that may impact cognitive recovery longer term.},
}

@article {pmid40933446,
year = {2025},
author = {Lee, SP and Kang, SY},
title = {Clinical outcomes of persistent cough following coronavirus disease 2019 infection: A 1-year retrospective cohort study.},
journal = {Asia Pacific allergy},
volume = {15},
number = {3},
pages = {186-191},
doi = {10.5415/apallergy.0000000000000188},
pmid = {40933446},
issn = {2233-8276},
abstract = {BACKGROUND: Cough is one of the multiple prolonged symptoms observed in patients who had coronavirus disease 2019 (COVID-19) infection.

OBJECTIVE: We assessed the clinical outcomes and identified factors contributing to cough persistence in patients post-COVID-19.

METHODS: This retrospective cohort study included adults who visited a specialist cough clinic between 2022 and 2023. All participants underwent systematic investigation and treatment for persistent cough. Cough persistence was assessed at the 2- and 12-month follow-ups. Participants were classified as having persistent cough if they had a current troublesome cough at the 2- and 12-month follow-ups, and a cough severity visual analog scale (VAS) score change below 30.

RESULTS: Sixty-six patients (mean age 48.7 years; 72.7% women) were analyzed and divided into 2 groups: persistent cough (33.3%) and remitted cough (66.7%). The persistent cough group had a significantly higher prevalence of abnormal laryngeal sensation, sputum production, breathing difficulty, and airway eosinophilia; their VAS score changes at 2 months were also lower. Multivariable analyses indicated associations between persistent cough at 1 year and factors such as airway eosinophilia (adjusted odds ratio [aOR], 6.78), abnormal laryngeal sensation (aOR, 6.42), and low cough VAS reduction (aOR, 1.05).

CONCLUSION: Persistent cough remained a significant issue for one-third of the patients after COVID-19. The clinical features commonly observed in chronic cough were also present in those who have experienced COVID-19, which contributed to prolonged cough. These findings underscore the need for systematic assessment and tailored treatment strategies to effectively manage persistent cough in patients post-COVID-19.},
}

@article {pmid40932810,
year = {2025},
author = {Cooper, E and Lound, A and Jones, K and Bruton, J and Day, S and Atchison, CJ and Eccles, C and Piper, A and Cooke, GS and Chadeau-Hyam, M and Elliott, P and Ward, H},
title = {Challenges of Inclusion: A Population-Based Interview Study of Long Covid.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70428},
doi = {10.1111/hex.70428},
pmid = {40932810},
issn = {1369-7625},
support = {//This study is independent research funded by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI): REACT-GE (Genomics England) (UKRI MC_PC_20049) and REACT-LC (Long Covid) (COV-LT-0040). The REACT-1 and REACT-2 studies were funded by the Department of Health and Social Care in England (DHSC). We also acknowledge support from the NIHR Imperial Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of DHSC, NIHR or UKRI./ ; },
abstract = {INTRODUCTION: People with long Covid report a wide range of symptoms and inconsistent responses when seeking clinical diagnosis and support. Much of the qualitative research on long Covid has been based on people attending specialist clinical services or who have accessed support groups. We aimed to understand the varied experiences of persistent symptoms following Covid-19 and the impact on the lives of people affected.

METHODS: Qualitative interview study nested within the large, community-based REal-time Assessment of Community Transmission (REACT) study in England. Participants reporting persistent symptoms following Covid-19 were asked for consent to be contacted about a follow-up interview. We then purposively sampled by age, gender, ethnicity and symptom severity and conducted 60 interviews. Analysis was carried out using a reflexive thematic analysis approach.

RESULTS: Participants were an ethnically diverse group aged between 18 and 80 years who reported symptoms following Covid-19 for between a few months and more than 2 years. Many had not accessed clinical care or specific long Covid support, and some did not identify with the category of long Covid, rendering their experiences largely invisible. Participants highlighted the ways in which they self-manage symptoms within this context, and the varied burden of coping with ongoing health problems.

CONCLUSION: This diverse sample of people with long Covid report a range of challenges managing this emerging and contested condition, with uncertainty affecting their own understanding and the validation they receive from professionals, family and friends. These challenges intersect with others, such as racism, and are compounded by a lack of specific resources for long Covid as well as over-stretched health services in the United Kingdom. Nevertheless, people report a variety of strategies in managing their symptoms, seeking information and support from a range of sources.

Study design, analysis and drafting of paper informed by Patient Advisory Group.},
}

@article {pmid40932654,
year = {2025},
author = {Gustavsson, E and Johnson, E and Levi, R},
title = {Towards a Less Ideal Theory About Well-being-The Case of Post COVID Condition.},
journal = {Journal of bioethical inquiry},
volume = {},
number = {},
pages = {},
pmid = {40932654},
issn = {1872-4353},
support = {Dnr 2021-01245//Vetenskapsrådet/ ; },
abstract = {Post COVID-19 Condition (PCC) is a complex condition presenting significant challenges for patients. Individuals suffering from severe PCC are often assessed in rehabilitation medicine departments or specialized post-COVID centres, where their condition is evaluated using the International Classification of Functioning, Disability and Health (ICF). The ICF framework primarily focuses on functional impairments, disabilities, and restrictions in participation, with an emphasis on the concept of "functioning." However, a critical question remains: how does this notion of functioning relate to the well-being of these individuals? This paper explores this issue by examining three fictionalized but typical case studies of PCC patients in relation to two distinct theoretical approaches. First, we engage with theories about well-being from the philosophy of well-being emphasizing the individual's perspective. Second, we explore relational approaches in bioethics and their theoretical underpinnings, which emphasize how people are situated, considering context and relations rather than purely individual conditions. The paper highlights the potential tensions between these approaches while arguing that a more comprehensive understanding of well-being can emerge by integrating insights from both traditions. Through the examination of PCC patient cases, we propose that well-being can be better understood when approached from multiple angles, enriching the understanding of patient outcomes in rehabilitation medicine.},
}

@article {pmid40932646,
year = {2025},
author = {Crevenna, R and Keilani, M},
title = {Correction to: Authors' response to the letter to the editor 'Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue'.},
journal = {Wiener klinische Wochenschrift},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00508-025-02603-w},
pmid = {40932646},
issn = {1613-7671},
}

@article {pmid40728640,
year = {2025},
author = {Crevenna, R and Keilani, M},
title = {Authors' response to the letter to the editor "Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue".},
journal = {Wiener klinische Wochenschrift},
volume = {},
number = {},
pages = {},
pmid = {40728640},
issn = {1613-7671},
}

@article {pmid40930270,
year = {2025},
author = {Walker, TA and Kohler, JZ and Haddad, MM},
title = {Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106108},
doi = {10.1016/j.bbi.2025.106108},
pmid = {40930270},
issn = {1090-2139},
}

@article {pmid40927706,
year = {2025},
author = {Sandoval, MN and Moore, LW and Huang, HJ and Graviss, EA},
title = {Long COVID risk factors and outcomes among solid organ transplant recipients: a retrospective cohort study.},
journal = {Frontiers in surgery},
volume = {12},
number = {},
pages = {1602167},
pmid = {40927706},
issn = {2296-875X},
abstract = {BACKGROUND: Solid organ transplant (SOT) recipients are not only at increased risk of morbidity and mortality due to acute COVID-19 but may also experience poor long-term outcomes due to post-acute COVID-19 syndromes, including long COVID.

METHODS: This retrospective, registry-based chart review evaluated graft failure and mortality among SOT recipients diagnosed with COVID-19 at a large, urban transplant center in Houston, Texas, USA. Patient populations were analyzed separately according to their long COVID status at the time of transplant to preserve the temporal relationship between the exposure (long COVID) and the outcome (graft failure or mortality).

RESULTS: In total, 146 (5%, 146/3,202) patients were diagnosed with long COVID, 443 (14%, 443/3,202) patients expired during the study period, and 202 (6%, 202/3,202) were diagnosed with graft failure. Overall, patients with long COVID were older, had an increased comorbidity burden, and were more likely to be lung, heart, or heart-lung recipients compared with those who were not diagnosed with long COVID. Long COVID was not significantly associated with death or graft failure in this study population, though relationships varied across subpopulations.

CONCLUSIONS: The observed differences between patients diagnosed with COVID-19 and long COVID before and after transplant warrant additional studies as the proportion of people with some SARS-CoV-2 infection history approaches 90%. Future investigations may prioritize longitudinal follow-up of long COVID patients diagnosed before or after transplant to determine specific etiologies of long-term morbidity and mortality.},
}

@article {pmid40927340,
year = {2025},
author = {Leitner, M and Paletta, L and Leal-Garcia, M and Fellner, M and Koini, M},
title = {A tablet-based intervention study to alleviate cognitive and psychological symptoms in patients with post-Covid-19 condition.},
journal = {Frontiers in psychology},
volume = {16},
number = {},
pages = {1582742},
pmid = {40927340},
issn = {1664-1078},
abstract = {BACKGROUND: Cognitive impairment and psychological complaints are among the most common consequences for patients suffering from Post-Covid-19 condition (PCC). As there are limited training options available, this study examined a longitudinal tablet-based training program addressing cognitive and psychological symptoms.

METHODS: Forty individuals aged between 36 and 71 years (M = 49.85, SD = 8.63; 80% female) were randomly assigned to either an intervention group (n = 20) or a waitlist control group (n = 20). The intervention group received a three-month tablet-based training program involving cognitive exercises, relaxation techniques, and physiotherapy exercises. Additionally, both groups underwent a thorough neuropsychological assessment (attention, memory, executive functions, word fluency, subjective cognitive complaints, fatigue, depression, anxiety, and quality of life) before the training, after 3 months of training, and after 6 months in order to assess long-term effects.

RESULTS: Pre-post comparisons revealed that individuals assigned to the intervention group (n = 18 after dropout), as compared to the control group (n = 16 after dropout), showed a reduction in subjective cognitive complaints (p < 0.001) as well as in depressive symptoms (p < 0.001). Additionally, their MoCA Memory Index Score remained stable (p = 0.496), while it declined significantly in the wait-list control group (p = 0.008). However, the training had no effect on the other domains assessed and not all training-related effects were stable over time. Finally, a higher number of post-Covid symptoms was negatively correlated with attention and memory capabilities (all p < 0.05), with a longer disease duration further amplifying the negative impact of post-Covid symptoms on memory performance.

CONCLUSION: Tablet-based training programs can help improve subjective complaints, depressive symptoms, and memory and may serve as an additional therapy option. Further studies are needed to investigate the stability of these effects.},
}

@article {pmid40926885,
year = {2025},
author = {Ferreira, LGJ and da Silva Almeida, I and Costa, RR and Roriz, GV and Geremia, JM and Durigan, JLQ and Marqueti, RC},
title = {Long COVID-19 alters muscle architecture and muscle-tendon force transmission: a one-year longitudinal study.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1641046},
pmid = {40926885},
issn = {1664-042X},
abstract = {INTRODUCTION: There are limited studies on the long-term effects of COVID-19 on skeletal muscle morphology and architecture. Therefore, this study aims to address this gap by assessing the effects of prior COVID-19 infection on quadriceps muscle architecture and tendon-aponeurosis complex (TAC) properties over a one-year period, comparing three cohorts: individuals with moderate COVID-19, individuals with severe COVID-19, and a healthy control group.

METHODS: Seventy participants were included in the study and allocated to three groups: moderate COVID-19 (n = 22), severe COVID-19 (n = 18), and control (n = 30). Four assessments were conducted over 1 year for the COVID groups. Maximal voluntary isometric (MVIC) knee extension contractions were performed on an isometric dynamometer, with simultaneous ultrasound imaging of the vastus lateralis (VL) and rectus femoris (RF) muscles. Fascicle length (FL) and pennation angle (PA) were obtained at rest and during MVIC, along with TAC displacement. Generalized Estimating Equation models were used to evaluate muscle variables, with "group" and "time" as factors. The model fit was adjusted, with 'torque' as a covariate.

RESULTS: Regarding muscle architecture, FL was greater in the severe COVID-19 group during early post-infection assessments for the RF at rest (p = 0.043). Additionally, both COVID-19 groups exhibited longer VL fascicles compared to controls (p = 0.032). TAC displacement was reduced in the severe COVID-19 group (RF: p = 0.008; VL: p = 0.047) compared to control. TAC stiffness did not differ between groups (p = 0.517), but torque production demonstrated an effect on this variable (p = 0.001). Both COVID-19 groups presented reduced PA for the VL at rest (p = 0.012) compared to control. Additionally, torque played a crucial role in influencing PA in both muscles, at rest and during contraction.

CONCLUSION: Participants with severe COVID-19 exhibited alterations in muscle architecture, which may contribute to persistent muscular weakness even one-year post-infection. The findings underscore the potential role of muscle strength, particularly the impact of torque on TAC stiffness and PA across all groups. Long COVID-19 rehabilitation and exercise physiologists should prioritize quadriceps strengthening strategies to restore muscle architecture and optimize force transmission.},
}

@article {pmid40926879,
year = {2025},
author = {Pienkos, S and Swank, Z and Hamlin, RE and Rao, M and Grant, P and Bonilla, H and Jacobson, K and Jagannathan, P and Singh, U and Walt, DR and Subramanian, A and Blish, C},
title = {Single-Cell and Plasma Proteomics Do Not Differentiate Patients With and Without SARS-CoV-2 Antigenemia in Convalescence in a Cohort of 100 Patients.},
journal = {Open forum infectious diseases},
volume = {12},
number = {9},
pages = {ofaf515},
pmid = {40926879},
issn = {2328-8957},
abstract = {Plasma samples obtained approximately 3 (n = 100) and 12 months (n = 78) after acute SARS-CoV-2 infection were tested for S1, spike, and N antigens. There were no significant differences in plasma proteins or single-cell protein expression levels on immune cells between those with and without plasma antigen detected.},
}

@article {pmid40924654,
year = {2025},
author = {Fazekas, C and Goswami, N and Matzer, F and Avian, A and Lodron, J and Rijksen, M and Hanfstingl, B and Kavcic, V and Groselj-Strele, A and Sourij, H and Kessler, HH and Stelzl, E and Voegel, CD and Binz, TM and Schmid-Zalaudek, K and Wittmann, A and Pilz, S},
title = {Perceived Chronic Stress prior to SARS-CoV-2 Infection Predicts Ongoing Symptomatic COVID-19: A Prospective Cohort Study.},
journal = {Psychotherapy and psychosomatics},
volume = {},
number = {},
pages = {1-12},
doi = {10.1159/000547858},
pmid = {40924654},
issn = {1423-0348},
abstract = {INTRODUCTION: Understanding chronic stress as a potential risk factor for COVID-19 progression could inform public health measures and personalized preventive interventions. Therefore, we investigated the influence of chronic stress prior to SARS-CoV-2 infection on symptom persistence 1 month after COVID-19 onset.

METHODS: The participants of this prospective cohort study named "StressLoC" were adults with COVID-19 who had tested positive for SARS-CoV-2 infection within the last 7 days. Pre-existing perceived chronic stress assessed by the Perceived Stress Scale (PSS-10) was the primary predictor. The number of stressful life events and hair cortisol concentration served as additional measures of pre-existing chronic stress. The main outcome was examined using the Long COVID Symptom and Impact Tool. It was defined as the presence of any new and impactful COVID-19-related symptom at month 1 after inclusion. Accordingly, participants were assigned to either the ongoing symptomatic COVID-19 group (OSC-G) or control group.

RESULTS: The study cohort comprised 288 participants (73.3% female), with a median age of 46 years (IQR 35-56). A total of 210 participants (72.9%) were categorized as OSC-G. Multivariate logistic regression showed that allocation to OSC-G was predicted by perceived chronic stress in the month prior to COVID-19 (OR: 1.08, 95% CI: 1.03-1.14; p = 0.002) and the number of pre-existing symptoms (OR: 1.08, 95% CI: 1.03-1.13; p = 0.001). The number of stressful life events and hair cortisol concentration did not predict OSC-G allocation.

CONCLUSIONS: Results suggest that higher levels of pre-existing perceived chronic stress increase the odds of developing ongoing symptomatic COVID-19.},
}

@article {pmid40924481,
year = {2025},
author = {Gabernet, G and Maciuch, J and Gygi, JP and Moore, JF and Hoch, A and Syphurs, C and Chu, T and Doni Jayavelu, N and Corry, DB and Kheradmand, F and Baden, LR and Sekaly, RP and McComsey, GA and Haddad, EK and Cairns, CB and Rouphael, N and Fernandez-Sesma, A and Simon, V and Metcalf, JP and Agudelo Higuita, NI and Hough, CL and Messer, WB and Davis, MM and Nadeau, KC and Pulendran, B and Kraft, M and Bime, C and Reed, EF and Schaenman, J and Erle, DJ and Calfee, CS and Atkinson, MA and Brakenridge, SC and Melamed, E and Shaw, AC and Hafler, DA and Augustine, AD and Becker, PM and Ozonoff, A and Bosinger, SE and Eckalbar, W and Maecker, HT and Kim-Schulze, S and Steen, H and Krammer, F and Westendorf, K and Network, I and Peters, B and Fourati, S and Altman, MC and Levy, O and Smolen, KK and Montgomery, RR and Diray-Arce, J and Kleinstein, SH and Guan, L and Ehrlich, LI},
title = {A multi-omics recovery factor predicts long COVID in the IMPACC study.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI193698},
pmid = {40924481},
issn = {1558-8238},
abstract = {BACKGROUND: Following SARS-CoV-2 infection, ~10-35% of COVID-19 patients experience long COVID (LC), in which debilitating symptoms persist for at least three months. Elucidating biologic underpinnings of LC could identify therapeutic opportunities.

METHODS: We utilized machine learning methods on biologic analytes provided over 12-months after hospital discharge from >500 COVID-19 patients in the IMPACC cohort to identify a multi-omics "recovery factor", trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood CyTOF protein levels. Recovery factor scores were tested for association with LC, disease severity, clinical parameters, and immune subset frequencies. Enrichment analyses identified biologic pathways associated with recovery factor scores.

RESULTS: LC participants had lower recovery factor scores compared to recovered participants. Recovery factor scores predicted LC as early as hospital admission, irrespective of acute COVID-19 severity. Biologic characterization revealed increased inflammatory mediators, elevated signatures of heme metabolism, and decreased androgenic steroids as predictive and ongoing biomarkers of LC. Lower recovery factor scores were associated with reduced lymphocyte and increased myeloid cell frequencies. The observed signatures are consistent with persistent inflammation driving anemia and stress erythropoiesis as major biologic underpinnings of LC.

CONCLUSION: The multi-omics recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.

CLINICALTRIALS: gov NCT04378777.

FUNDING: This study was funded by NIH, NIAID and NSF.},
}

@article {pmid40924424,
year = {2025},
author = {Lin, JC and McCarthy, M and Potluri, S and Nguyen, D and Yan, R and Aysola, J},
title = {Long COVID and Food Insecurity in US Adults, 2022-2023.},
journal = {JAMA network open},
volume = {8},
number = {9},
pages = {e2530730},
doi = {10.1001/jamanetworkopen.2025.30730},
pmid = {40924424},
issn = {2574-3805},
mesh = {Humans ; *Food Insecurity ; *COVID-19/epidemiology/complications ; Female ; Male ; Adult ; Cross-Sectional Studies ; Middle Aged ; United States/epidemiology ; Food Assistance/statistics & numerical data ; Retrospective Studies ; SARS-CoV-2 ; Aged ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Young Adult ; *Food Supply/statistics & numerical data ; },
abstract = {IMPORTANCE: Long COVID (ie, post-COVID-19 condition) is a substantial public health concern, and its association with health-related social needs, such as food insecurity, remains poorly understood. Identifying modifiable risk factors like food insecurity and interventions like food assistance programs is critical for reducing the health burden of long COVID.

OBJECTIVE: To investigate the association of food insecurity with long COVID and to assess the modifying factors of Supplemental Nutrition Assistance Program (SNAP) participation and employment status.

This retrospective, cross-sectional survey study used data from the 2022 to 2023 National Health Interview Survey. Respondents aged 18 years and older who reported prior COVID-19 infection and responded to questions on food insecurity and long COVID were included.

EXPOSURE: Food insecurity, categorized as food secure or food insecure.

MAIN OUTCOMES AND MEASURES: The primary outcome was current long COVID, defined as symptoms lasting 3 or more months after initial COVID-19 infection persisting to time of interview. The secondary outcome was long COVID recovery, indicating history of long COVID without current symptoms. Food insecurity was measured using the validated 10-item National Center for Health Statistics food insecurity scale. Odds ratios (ORs) and 95% CIs for the association of food insecurity with long COVID were calculated using simple and multiple logistic regression.

RESULTS: The study enrolled 21 631 participants (1255 female [weighted percentage, 53%]; 5058 aged 65 years or older [weighted percentage, 16%]), including 19 824 with food security and 1807 with food insecurity. In total, 288 respondents with food insecurity (weighted percentage, 15%) reported current long COVID compared with 1547 (weighted percentage, 7%) without food insecurity. Food insecurity was positively associated with current long COVID (adjusted OR, 1.73; 95% CI, 1.39-2.15) and negatively associated with recovery among adults with prior long COVID (adjusted OR, 0.70; 95% CI, 0.54-0.92). SNAP participation (P for interaction = .04) and unemployment (P for interaction = .04) significantly modified these associations.

CONCLUSIONS AND RELEVANCE: In this survey study of US adults with prior COVID-19 infection, food insecurity was associated with greater odds of long COVID and lower odds of recovery, with SNAP participation and unemployment mitigating these associations. These findings suggest that expanding SNAP eligibility, simplifying enrollment processes, and increasing awareness of food assistance programs may reduce the burden of food insecurity and long COVID and further emphasize the importance of addressing health-related social needs in chronic disease prevention and management.},
}

Humans
*Food Insecurity
*COVID-19/epidemiology/complications
Female
Male
Adult
Cross-Sectional Studies
Middle Aged
United States/epidemiology
Food Assistance/statistics & numerical data
Retrospective Studies
SARS-CoV-2
Aged
Risk Factors
Post-Acute COVID-19 Syndrome
Young Adult
*Food Supply/statistics & numerical data

@article {pmid40922860,
year = {2025},
author = {Potluri, S and Chittiprol, N and Varaganti, V and Avr, V and Vadakedath, S and Arvapally, D and Vemulapalli, C and Begum, GS and Madamsetti, N and Kandi, V},
title = {The Association of SARS-CoV-2 Infection and COVID-19 Vaccination With Sudden Death: An Explorative Review.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89527},
pmid = {40922860},
issn = {2168-8184},
abstract = {Since its discovery, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become the epicenter of public health concern. This was mainly attributed to the complexity of COVID-19 that resulted in variable disease progression with some developing asymptomatic infections, some suffering mild to moderate infections that resolved without the need for hospitalizations, and a few infected persons developing severe infections that required intensive care unit (ICU) admission and mechanical ventilation. The COVID-19 pandemic spread globally, affecting billions of people and killing millions. Most of the consequences were related to the novelty of the virus, poor understanding of its pathogenesis, and the lack of a specific antiviral drug and vaccine. The vaccines, although manufactured and made available to the public, were approved for emergency use before the completion of human clinical trials. Moreover, the continuous emergence of viruses following mutations resulted in the emergence of viral variants. This has led to doubts over the efficacy of vaccines. Vaccine inequity, represented by the disproportionate availability and distribution of vaccines among the rich and poor, concerns over long-term safety, and hesitancy, affected COVID-19 vaccination, thereby increasing the spread of SARS-CoV-2. Although the COVID-19 pandemic is no longer considered a public health emergency of international concern (PHEIC), the repercussions of the pandemic are still evident in the form of long COVID and post-COVID functional health status (PCFHS), wherein individuals who were previously infected continue to suffer organ dysfunction, primarily affecting the lungs and other organs of the body. During and after the pandemic, COVID-19 and probably vaccination were attributed to the death of many individuals, which were categorized as sudden death (SD) and sudden unnatural death (SUD). It is unclear if these deaths were a result of previous SARS-CoV-2 infection and prior COVID-19 vaccination or both. There are several instances of infected and recovered individuals who were healthy but suddenly developed complications and died. Through this explorative review, we aim to comprehend the role that SARS-CoV-2 infection and/or COVID-19 vaccination play in predisposing people to cardiovascular system (CVS) and central nervous system (CNS) disorders that can result in SD and SUD.},
}

@article {pmid40922488,
year = {2025},
author = {White, RA and Nygaard, AB and Søraas, A and Nyborg, GA},
title = {Excess all-cause mortality in Norway in 2024.},
journal = {Scandinavian journal of public health},
volume = {},
number = {},
pages = {14034948251371830},
doi = {10.1177/14034948251371830},
pmid = {40922488},
issn = {1651-1905},
abstract = {AIMS: The Norwegian Institute of Public Health calculated excess mortality for Norway in 2024 using a reference period that included 2023-a year with significant excess mortality-and concluded there was no excess mortality in 2024. This study estimates excess mortality in 2024 using only pre-pandemic years as the reference, providing a basis for identifying excess COVID-19 related mortality.

METHODS: We estimated excess mortality in 2024 using a negative binomial model trained on 2010-2019 data. Deaths were modelled by age (0, 1-19, 20-39, 40-64, 65-79, 80-89 and 90+ years) and sex, with population offsets. Expected mortality was projected using both a conservative approach where the prediction for 2023 was carried forward to 2024 and a non-conservative linear extrapolation to 2024.

RESULTS: The conservative approach estimated 2898 excess deaths (7.0%; 95% prediction interval (PI), 4.9-9.1%) in 2024. Significant excess mortality was observed in age groups 1-19 (45 deaths; 36.6% excess), 20-39 (107 deaths; 17.6% excess), 40-64 (439 deaths; 10.6% excess) and 65-79 (1631 deaths; 13.7% excess). Ages 1-39 and 40-64 accounted for approximately 5% and 15% of total excess mortality, respectively.

CONCLUSIONS: Persistent excess mortality from 2022 to 2024 suggests a new elevated mortality baseline and a reduction or reversal of Norway's pre-pandemic mortality decline. Although multiple factors may contribute, given sustained excess mortality since 2022, our findings suggest that the unmitigated spread of SARS-CoV-2 in Norway since 2022 can be associated with increased mortality, particularly for those under 65.},
}

@article {pmid40922273,
year = {2025},
author = {Pires, L and Marreiros, A and Saraiva, C and Reis, C and Neves, D and Guerreiro, C and Tomé, JB and Luz, MI and Pereira, MI and Barroso, AS and Ferreira, J and Gonzalez, LM and Moniri, A and Drummond, M and Berger-Estilita, J},
title = {Association of acute COVID-19 severity and long COVID fatigue and quality of life: Prospective cohort multicenter observational study.},
journal = {Medicine},
volume = {104},
number = {36},
pages = {e42891},
doi = {10.1097/MD.0000000000042891},
pmid = {40922273},
issn = {1536-5964},
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/complications/psychology/epidemiology ; Male ; Female ; *Fatigue/etiology/epidemiology/psychology ; Prospective Studies ; Middle Aged ; Severity of Illness Index ; Anxiety/epidemiology/etiology ; Adult ; Depression/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; Portugal/epidemiology ; },
abstract = {Long COVID, or post-COVID-19 condition, is characterized by symptoms persisting beyond 12 weeks after severe acute respiratory syndrome coronavirus 2 infection, affecting individuals regardless of acute disease severity. Fatigue - often linked with depression and anxiety - is among its most debilitating manifestations. However, the associations between fatigue subtypes (physical vs mental), mental health symptoms, and acute disease severity on long-term health-related quality of life (HRQoL) remain unclear. This study examines the relationships between long COVID fatigue, depression, anxiety, acute disease severity, and HRQoL in a post-COVID-19 cohort. This prospective observational cohort study was conducted across 5 Portuguese hospitals between November 2020 and June 2022. Adults (≥18 years) with confirmed severe acute respiratory syndrome coronavirus 2 infection ≥6 months prior and fulfilling World Health Organization criteria for long COVID were included. Acute Coronavirus disease 2019 (COVID-19) severity was classified per World Health Organization definitions. The sampling strategy included patients across the severity spectrum. At 3 months postinfection (T1), patients received physician-led clinical assessments. At 6 months (T2), they attended in-person follow-up visits, completing standardized forms and validated questionnaires assessing post-acute sequelae. Fatigue was reported both binarily (yes/no) and via the chalder fatigue scale (11-item version). Anxiety and depression were assessed using the hospital anxiety and depression scale; post-traumatic stress disorder symptoms with the 14-item post-traumatic stress scale; and HRQoL with the EuroQol-5 dimensions. Descriptive statistics, analysis of variance, chi-square, and correlation analyses (Pearson's or Spearman's) were used to evaluate associations. Analyses were performed using SPSS (v27; IBM Corp., Amonk). Among 208 patients, fatigue was significantly associated with anxiety and depression (P < .001). Physical fatigue correlated more strongly with depression (r = 0.65, P < .001) and anxiety (r = 0.58, P < .001) than mental fatigue (r = 0.50 and R = 0.48, respectively; P < .001). Surprisingly, severe acute COVID-19 cases reported lower fatigue (CFQ: 13.3 ± 8.4) than mild (17.7 ± 7.2) or moderate (17.4 ± 8.0) cases (P < .005), and higher HRQoL (EuroQol visual analog scale: 74.3 ± 20.3, P = .002). Anxiety symptoms were more common in mild cases (P < .001); post-traumatic stress disorder symptoms did not differ by severity. Long COVID fatigue - especially physical - is strongly linked to depression and anxiety. Mild/moderate acute COVID-19 cases show greater fatigue and lower HRQoL than severe cases, highlighting the need for tailored long-term care regardless of initial severity.},
}

Humans
*Quality of Life/psychology
*COVID-19/complications/psychology/epidemiology
Male
Female
*Fatigue/etiology/epidemiology/psychology
Prospective Studies
Middle Aged
Severity of Illness Index
Anxiety/epidemiology/etiology
Adult
Depression/epidemiology/etiology
Post-Acute COVID-19 Syndrome
Aged
SARS-CoV-2
Portugal/epidemiology

@article {pmid40921327,
year = {2025},
author = {Claudio, FD and Vallejo, N and Mateu, L and Bayes-Genis, A and Delgado, V and Teis, A},
title = {Chest pain in long covid disease. Insights from stress cardiovascular magnetic resonance.},
journal = {Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.repc.2025.03.008},
pmid = {40921327},
issn = {2174-2030},
}

@article {pmid40920586,
year = {2025},
author = {Orlinick, B and Mehta, S and McAlpine, L and Khoshbakht, S and Fertuzinhos, S and Nelson, A and Chiarella, J and Das, B and Patel, V and Filippidis, P and Corley, MJ and Spudich, SS and Farhadian, SF},
title = {CSF immune cell alterations in women with neuropsychiatric Long COVID.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf468},
pmid = {40920586},
issn = {1537-6613},
abstract = {BACKGROUND: Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19. However, whether there are central nervous system-specific changes in gene expression in women with neuropsychiatric Long COVID (NP-Long COVID) remains unknown.

METHODS: Twenty-two women with and ten women without NP-Long COVID were enrolled from New Haven, CT, and the surrounding region and consented to a blood draw and large volume lumbar puncture. Total RNA was extracted from cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMC). Polyadenylated RNA was sequenced, and differential expression analyses were performed.

RESULTS: Both CSF and PBMC samples showed differential gene expression associated with Long COVID status. There were CSF-specific differentially expressed genes (DEGs) in people with Long COVID, including in genes related to oxidative stress, reactive oxygen species, and P53 response, indicating compartment-specific immune responses. Some pathways were dysregulated in both the CSF and PBMC of Long COVID compared to controls, including those related to androgen response, MTORC1 signaling, and lipid metabolism.

CONCLUSIONS: Women with NP-long COVID show compartment-specific, transcriptional profiles in the CSF with evidence of enrichment in cellular stress pathways. These results underscore the importance of examining CSF-specific molecular profiles to better understand post-viral neurological syndromes.},
}

@article {pmid40918941,
year = {2025},
author = {Bunnell, HT and Reedy, C and Lorman, V and Jhaveri, R and Rivera-Sepulveda, A and Salamon, KS and Patel, PB and Morse, KE and Davenport, MA and Cowell, LG and Utidjian, L and Christakis, DA and Rao, S and Sills, MR and Case, A and Mendonca, EA and Taylor, BW and Rutter, J and Martinez, AT and Letts, R and Bailey, LC and Forrest, CB and , },
title = {A natural language processing pipeline for identifying pediatric long COVID symptoms and functional impacts in freeform clinical notes: a RECOVER study.},
journal = {JAMIA open},
volume = {8},
number = {5},
pages = {ooaf089},
pmid = {40918941},
issn = {2574-2531},
abstract = {OBJECTIVE: To develop a natural language processing (NLP) pipeline for unstructured electronic health record (EHR) data to identify symptoms and functional impacts associated with Long COVID in children.

MATERIALS AND METHODS: We analyzed 48 287 outpatient progress notes from 10 618 pediatric patients from 12 institutions. We evaluated notes obtained 28 to 179 days after a COVID-19 diagnosis or positive test. Two samples were examined: patients with evidence of Long COVID and patients with acute COVID but no evidence of Long COVID based on diagnostic codes. The pipeline identified clinical concepts associated with 21 symptoms and 4 functional impact categories. Subject matter experts (SMEs) screened a sample of 4586 terms from the NLP output to assess pipeline accuracy. Prevalence and concordance of each of the 25 concepts was compared between the 2 patient samples.

RESULTS: A binary assertion measure comparing SME and NLP assertions showed moderate accuracy (N = 4133; F1 = .80) and improved substantially when only high-confidence SME assertions were considered (N = 2043; F1 = .90). Overall, the 25 Long COVID concept categories were markedly more prevalent in the presumptive Long COVID cohort, and differences were noted between concepts identified in notes versus structured data.

DISCUSSION: This preliminary analysis illustrates the additional insight into a syndrome such as Long COVID gained from incorporating notes data, characterizing symptoms and functional impacts.

CONCLUSION: These data support the importance of incorporating NLP methodology when possible into designing computable phenotypes and to accurately characterize patients with Long COVID.},
}

@article {pmid40918680,
year = {2025},
author = {Sadat Larijani, M and Bavand, A and Ashrafian, F and Moradi, L and Ramezani, A},
title = {Late-Induced Autoimmune Disorders Post-COVID-19 Vaccination/Infection: Case Report From Iran.},
journal = {Case reports in medicine},
volume = {2025},
number = {},
pages = {8815875},
pmid = {40918680},
issn = {1687-9627},
abstract = {COVID-19 pandemic led to a fast vaccine design due to the threat of rapid spreading worldwide. Safety profile of the approved vaccines has been achieved mostly through clinical trials. However, some unsolicited adverse events in a longer duration of time have been recorded in addition to the late disorders known as long-COVID, stemming from classical infection. Therefore, case studies and long-term follow-up are required to enrich the current data on SARS-COV-2 infection/vaccination. In this study, two cases of autoimmune diseases induced by COVID-19 and/or vaccination were followed in three years. The profile of each is presented, and the probable cause has been discussed. The laboratory findings approved systematic lupus erythematosus and Hashimoto's thyroiditis in the studied cases. The key finding of this study is that the importance of probable autoimmune diseases flares up in individuals with a history of autoimmunity in their families which could manifest as a long-COVID symptom or late vaccination side effect.},
}

@article {pmid40917843,
year = {2025},
author = {Gu, L and Yue, J and Lin, J and Liu, Z and Huang, JA},
title = {Challenges in diagnosis and treatment of long COVID.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1641411},
pmid = {40917843},
issn = {2296-858X},
abstract = {Despite a large population affected by COVID-19, awareness of long COVID among clinicians is surprisingly limited. This has led to delayed or missed diagnoses and, consequently, inappropriate treatments that fail to address patients' specific needs. Our study highlights the gaps in knowledge and the barriers to effective management of long COVID in the healthcare system. Through this work, we aim to bring attention to these critical issues and advocate for urgent action to improve the clinical management of long COVID.},
}

@article {pmid40894014,
year = {2025},
author = {Abramoff, B and Dillingham, T and Rybicki, AK and Shofer, F and McGinley, E and Verma, SS and Kuns, MC and Barry, JT and Pezzin, LE},
title = {Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program to Improve the Functioning of Persons Suffering from Post-acute Sequelae of SARS-CoV-2 infection (PASC): A Randomized Controlled Trial.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40894014},
issn = {2693-5015},
support = {R01 HD108312/HD/NICHD NIH HHS/United States ; },
abstract = {BACKGROUND: About 10-20% of persons who contract SARS CoV-2 will experience persistent post-acute sequelae of SARSCoV-2 infection (referred here as PASC). Given that persistent symptoms are heterogeneous with multisystem involvement, recent consensus recommendations suggest that a holistic rehabilitation program may be required to manage PASC and restore function. While treatments offered at emerging outpatient COVID recovery clinics are being informed by previous similar diseases, the need is great for a better understanding of the unique needs of this growing population and for tested, efficacious rehabilitation programs to address them.

METHODS/DESIGN: Data from a large and diverse ongoing longitudinal survey of persons positive for COVID-19 at the study health system will serve as the sampling frame from which to enroll PASC study patients. The targeted six-week program will comprise a core set of therapies including individually titrated isometrics, strengthening of accessory breathing muscles and diaphragm, resistance and aerobic conditioning, and neuropsychological and cognitive remediation tailored to patients' needs. Using a randomized controlled trial design, the effectiveness of the supervised multimodal rehabilitation intervention will be compared to that of a self-guided (active control) group receiving patient education materials adapted from the World Health Organization guidelines for PASC management. In addition to walking speed, a widely used global measure of aerobic capacity and endurance, and patient-reported health and functioning (primary outcomes), we will assess intervention effectiveness on: cognitive functioning, pain, fatigue, tension, stress, anxiety, and depression, and self-management of PASC symptoms (secondary outcomes). Outcomes will be measured at 8 weeks and at 90 day's post- study entry to examine sustainability of effects. Recruitment is ongoing.

DISCUSSION: It is unlikely that COVID-19 vaccines will lead to the end of PASC syndrome given the emergence of increasingly infectious variants and the high numbers of individuals with continued symptoms several months from initial infection. High rates of vaccine hesitancy and refusal will also contribute to the persistence of both COVID-19 and PASC. Given the dearth of rigorous scientific evidence regarding effective assessment and treatment of PASC and unresolved questions concerning post-COVID rehabilitation care, the results of this study will have significant implications for both policy and program development.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06156202.},
}

@article {pmid40914478,
year = {2025},
author = {Houweling, L and Holtjer, JCS and Bloemsma, LD and de Jong, PA and Mohamed Hoesein, FA and Nossent, EJ and Vermeulen, RCH and Maitland-Van der Zee, AH and Downward, GS},
title = {Air pollution and long COVID: association with pulmonary function and radiological abnormalities 3-15 months post-COVID.},
journal = {Environmental research},
volume = {},
number = {},
pages = {122707},
doi = {10.1016/j.envres.2025.122707},
pmid = {40914478},
issn = {1096-0953},
abstract = {While studies have examined associations between air pollution and subjective long COVID outcomes such as fatigue and symptoms, no studies have focused on objective lung health measures. This study aimed to assess the impact of air pollution, examined through different exposure methods (exposures assigned via geospatial model, versus residential and personal measurements) on pulmonary function and radiological abnormalities in long COVID patients. We recruited 95 patients who attended a hospital outpatient clinic 3-6 months post-infection, during which pulmonary function was assessed via spirometry (FEV1,FVC,FEV1/FVC ratio) and diffusion capacity for carbon monoxide (DLCO), along with a chest CT. Of these, 38 patients with abnormalities in one of the assessed modalities returned for a follow-up visit approximately nine months later. Ambient levels of PM2.5, PM10, NO2, and O3 was assigned using land-use regression models, while residential and personal PM2.5 measurements were collected between the hospital visits in the participants' home environments. No associations were found between residential (assigned or measured) air pollution exposure and pulmonary function or radiological abnormalities at the first visit. Pulmonary function also typically improved between the first and second visit. However, an association between personal exposure and CT abnormalities was observed. A one IQR(12.3 μg/m[3]) increase in personal PM2.5 significantly increased the risk of airway abnormalities during the follow-up visit (adjusted OR:3.35, 95%CI:1.03,14.63), particularly mosaic patterns (OR:5.74, 95%CI:1.43,40.62). These findings add to evidence of exposure to air pollution playing a role in long COVID and call for mitigation measures to improve air quality.},
}

@article {pmid40914131,
year = {2025},
author = {Dixon, BE and Allen, KS and Simmons, N and Brinkley, J and Andrews, JG and Dzomba, BJ and Feiler, MO and Jones, RM and Ortiz, MR and Sharma, V and Dalton, AF and Pratt, C and Grannis, SJ and Saydah, SH and , },
title = {Incidence of long COVID among U.S. children and adults during the omicron era - Tracking Post-COVID Conditions (Track-PCC) network, 2022-2023.},
journal = {Journal of infection and public health},
volume = {18},
number = {11},
pages = {102935},
doi = {10.1016/j.jiph.2025.102935},
pmid = {40914131},
issn = {1876-035X},
abstract = {BACKGROUND: Long COVID, or Post-COVID Conditions (PCC), refers to new and persisting sequelae occurring in the months following an acute SARS-CoV-2 infection. Although previous studies have reported estimates of PCC incidence, few have examined trends during the Omicron variant period or have included geographically distinct regions for the same time periods.

METHODS: Track PCC is a surveillance network, leveraging electronic health records and public health data to monitor incidence over time across five diverse geographic sites in the U.S. This study examines the incidence of PCC in children and adults during the Omicron predominance period (January 1, 2022, to December 31, 2023) through April 2024. Incident conditions were identified using diagnostic codes for 49 conditions. Crude and adjusted incidence for the occurrence of PCC per 1000 person-days was calculated independently during three post-acute time periods: 31-90 days, 91-180 days, and 181-365 days. Incidence of PCC per 1000 person-days was also calculated by demographic and clinical characteristics.

RESULTS: The Track PCC network included 438,491 adults and 85,264 children with COVID-19 during the Omicron period. PCC incidence was highest 31-90 days post-acute; range from 2.95 to 5.05 per 1000 person-days among adults and 1.53-3.15 per 1000 person-days among children. Incidence was higher among older patients and patients with 3 or more co-morbidities and generally stable across variant sublineage periods.

CONCLUSION: These data suggest the PCC incidence following acute COVID-19 has not increased during the Omicron period. This is useful for understanding the burden of PCC and estimating demand of medical services following acute COVID-19 infections. PCC surveillance, including tracking the incidence of PCC, understanding patients at higher likelihood of developing PCC, and creating robust estimates, is critical to public health efforts to understand disease burden and guide prevention and treatment efforts.},
}

@article {pmid40910585,
year = {2025},
author = {Hu, C and Son, J and McAlpine, L and Walker, ELS and Dahl, M and Song, E and Ferreira Brito, S and Kavak, K and Onomichi, K and Bar-Or, A and Perrone, C and Riley, CS and Weinstock-Guttman, B and De Jager, PL and Longbrake, EE and Xia, Z},
title = {Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70184},
pmid = {40910585},
issn = {2328-9503},
support = {R01NS098023//National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS124882//National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
abstract = {BACKGROUND: Managing long COVID in people with multiple sclerosis and related disorders (pwMSRD) is complex due to overlapping symptoms. To address evidence gaps, we evaluated long COVID susceptibility in pwMSRD versus controls and its associations with multi-domain function and disability.

METHODS: In this multicenter cross-sectional study, participants completed a survey covering 71 post-infection symptoms, distinguishing new-onset from worsening symptoms. We defined long COVID using the 2024 NASEM criteria. Logistic regression assessed long COVID odds. Linear and Poisson regression evaluated associations with function and disability.

RESULTS: 969 pwMSRD (82.5% female, mean age 51.8 years, 63.5% infected) and 1003 controls (79.4% female, mean age 45.2 years, 61.2% infected) were included. PwMSRD had higher odds of long COVID (aOR = 1.6 [1.2-2.1]), with a stronger association when restricting to worsening symptoms (aOR = 2.3 [1.7-3.1]). Having long COVID was associated with worse physical function, cognition, and depression in both groups. PwMSRD with long COVID experienced greater physical function declines and more depression severity exacerbation than controls, and had faster disability progression compared to those without long COVID.

CONCLUSION: PwMSRD show increased susceptibility to long COVID, primarily driven by worsening symptoms. Long COVID contributes to more functional decline and disability worsening. Recognizing and managing long COVID is essential for pwMSRD.},
}

@article {pmid40910058,
year = {2025},
author = {Mazzali, C and Magnoni, P and Zucchi, A and Maifredi, G and Cavalieri d'Oro, L and Gambino, ML and Fanetti, AC and Perotti, PG and Villa, M and Valsecchi, MG and Vigani, D and Lucifora, C and Russo, AG},
title = {Strategies for population-level identification of post-acute sequelae of COVID-19 through health administrative data.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1637112},
pmid = {40910058},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 (PASC) encompass several clinical outcomes, from new-onset symptoms to both acute and chronic diagnoses, including pulmonary and extrapulmonary manifestations. Health administrative data (HAD) from health information systems allow population-level analyses of such outcomes. Our primary aim was to identify clinical conditions potentially attributable to SARS-CoV-2 infection, and the types of HAD and "diagnostic criteria" used for their detection.

METHODS: We performed a literature review to identify HAD-based cohort studies assessing the association between SARS-CoV-2 infection and medium-/long-term outcomes in the general population. From each included study, we extracted data on design, algorithms used for outcome identification (sources, coding systems, codes, time criteria/thresholds), and whether significant associations with SARS-CoV-2 infection were reported.

RESULTS: We identified six studies investigating acute and chronic conditions grouped by clinical domain (cardiovascular, respiratory, neurologic, mental health, endocrine/metabolic, pediatric, miscellaneous). Two studies also addressed the onset of specific symptoms. Cardio/cerebrovascular conditions were most studied, with significant associations reported for deep vein thrombosis, heart failure, atrial fibrillation, and coronary artery disease. Conditions in other domains were less investigated, with inconsistent findings. Only three studies were designed as test-positive vs. test-negative comparisons.

DISCUSSION: Heterogeneity in data sources, study design, and outcome definitions hinder the comparability of studies and explain the inconsistencies in findings about associations with SARS-CoV-2 infection. Rigorously designed studies on large populations with wide availability of data from health information systems are needed for population-level analyses on PASC, and especially on its impact on chronic diseases and their future burden on healthcare systems.},
}

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

@article {pmid40909985,
year = {2025},
author = {Salker, P},
title = {My Long COVID Journey - How To Slay Dragons Using Neuroplasticity.},
journal = {Journal of lifestyle medicine},
volume = {15},
number = {2},
pages = {87-89},
pmid = {40909985},
issn = {2234-8549},
abstract = {Framed through the long COVID experience of a United Kingdom physician, this narrative delineates the neurobiological consequences of chronic stress and highlights the role of neuroplastic interventions in facilitating physiological and cognitive recovery.},
}

@article {pmid40909835,
year = {2025},
author = {Chen, Z and Li, B and Chen, Y and Liu, J and Luo, F and Ogunyemi, KO and Ge, Y and Ke, Y and Yang, Y and Chen, X and Shen, Y},
title = {Mapping Long COVID: Spatial and Social Inequities Across the United States.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.21.25334183},
pmid = {40909835},
abstract = {Background Long COVID affects a substantial portion of the U.S. population, yet its spatiotemporal distribution remains poorly characterized. The emergence of the Omicron variant and persistent sociodemographic disparities may contribute to regional variation in long COVID risk. Understanding the patterns of long COVID is essential to implementing targeted and equitable public health interventions. Methods This retrospective study utilized data from the National COVID Cohort Collaborative (N3C), covering 5,652,474 COVID-19 cases and 41,694 long COVID cases across 1,063 U.S. counties from 2021 to 2024. Temporal patterns of long COVID were analyzed before and after the Omicron variant's emergence, and spatial patterns were assessed using Moran's I and Getis statistics. Bayesian spatial random effect models were employed to evaluate the associations between long COVID incidence and sociodemographic factors such as economic vulnerability, healthcare access, and mobility. Findings Quarterly long COVID incidence ranged from 0.015% to 14.29%. Before the emergence of the Omicron variant, incidence was 204 cases per 10,000 COVID-19 cases, compared with 248 cases per 10,000 COVID-19 cases after Omicron emergence (p < 0.001). After Omicron's emergence, 48.8% [328 of 673] of counties showed significant spatial correlation (p < 0.05), up from 43.5% [293 of 673] prior. High-risk areas became more concentrated in inland regions, while low-risk areas clustered along the East Coast. Long COVID incidence was significantly associated with economic vulnerability, limited healthcare access, and mobility constraints, with these sociodemographic disparities consistently driving its spatial disparities over time. Interpretation These findings underscore the need to address spatial and social inequities in long COVID risk. Targeted public health interventions, particularly in economically and geographically vulnerable regions, are essential to ensure equitable access to diagnosis, care, and resource allocation.},
}

@article {pmid40909786,
year = {2025},
author = {Wei, WQ and Guardo, C and Zhang, X and Gandireddy, S and Yan, C and Kerchberger, V and Dickson, A and Pfaff, E and Master, H and Basford, M and Chute, C and Tran, N and Manusco, S and Syed, T and Zhao, Z and Feng, Q and Haendel, M and Lunt, C and Harris, P and Li, L and Ginsburg, G and Denny, J and Roden, D},
title = {Multi-scale Data Improves Performance of Machine Learning Model for Long COVID Prediction.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7234976/v1},
pmid = {40909786},
issn = {2693-5015},
abstract = {Long COVID affects a substantial proportion of the over 778 million individuals infected with SARS-CoV-2, yet predictive models remain limited in scope. While existing efforts, such as the National COVID Cohort Collaborative (N3C), have leveraged electronic health record (EHR) data for risk prediction, accumulating evidence points to additional contributions from social, behavioral, and genetic factors. Using a diverse cohort of SARS-CoV-2-infected individuals (n>17,200) from the NIH All of Us Research Program, we investigated whether integrating EHR data with survey-based and genomic information improves model performance. Our multi-scale approach outperformed EHR-only models original AUROC 0.736 (95% CI: 0.730, 0.741), achieving an AUROC of 0.748 (0.741,0.755). Among the top predictors, active-duty service status, self-reported fatigue, and chr19:4719431:G:A_A were among the most informative survey and genetic features. These findings highlight the importance of incorporating multi-scale data to improve risk stratification and inform personalized interventions for long COVID.},
}

@article {pmid40908845,
year = {2025},
author = {Leighton, J and Nelson, MLA and Sheppard, CL and Wasilewski, M and Reis, L and Vijayakumar, A and Hitzig, SL and Robinson, LL and Levy, C and Ho, C and Steinberg, R and Goulding, S and Simpson, R},
title = {'You're alive, but are you living?' Exploring long COVID (LC)'s impact on social and leisure well-being for individuals and caregivers.},
journal = {Psychology & health},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/08870446.2025.2552233},
pmid = {40908845},
issn = {1476-8321},
abstract = {Long COVID (LC) affects physical health and cognition, limiting participation in social and leisure activities. As a novel disabling condition following a COVID-19 infection, informal caregivers of those with LC have taken on expanded roles, including educating themselves on this diagnosis. Gathering insights from people living with LC (PWLC) and their caregivers is crucial for understanding its impact on well-being and identifying targeted rehabilitation practices across the LC care pathway. Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with LC and 15 caregivers). Results: Composite narratives were created to introduce three key themes: (1) The demands of managing physical and cognitive symptoms of LC limit the ability of PWLC and caregivers to engage in social and leisure activities; (2) The loss of meaningful social and leisure activities deepens a diminished sense of identity for PWLC and caregivers; and (3) The absence of shared social and leisure engagement intensifies feelings of disconnection and loneliness for PWLC and caregivers. The findings support a need for more social- and leisure-targeted interventions for LC rehabilitation to help to optimize efforts for coping with the psychosocial impacts of living with, or caring for someone with, LC.},
}

@article {pmid40908304,
year = {2025},
author = {Ivković, V and Anandh, U and Bell, S and Kronbichler, A and Soler, MJ and Bruchfeld, A},
title = {Long COVID and the kidney.},
journal = {Nature reviews. Nephrology},
volume = {},
number = {},
pages = {},
pmid = {40908304},
issn = {1759-507X},
abstract = {Long coronavirus disease (COVID) - commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis - is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.},
}

@article {pmid40908194,
year = {2025},
author = {Colombo, C and Medino, P and Cipolli, M and Lucca, F and Cucchetto, G and Alghisi, F and Ciciriello, F and Sepe, A and Romano, C and Taccetti, G and Francalanci, M and Ambroni, M and Donati, V and Pizzamiglio, G and Spotti, M and Rotolo, N and Lucanto, MC and Cristadoro, S and Ficili, F and Leonetti, G and Giordano, P and Bignamini, E and Rizza, E and Pisi, G and Fainardi, V and Casciaro, R and Formigoni, C and Ros, M and Comello, I and Poli, P and Vitullo, P and Messore, B and Riberi, L and Palladino, N and Rosazza, C and Alicandro, G and Blasi, F},
title = {COVID-19 in people with Cystic Fibrosis beyond the pre-omicron era: a prospective study with a specific focus on long COVID.},
journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcf.2025.08.015},
pmid = {40908194},
issn = {1873-5010},
abstract = {BACKGROUND: The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF.

METHODS: This prospective, multicentre study enrolled individuals with confirmed SARS-CoV-2 infection between July 2021 and October 2022. Data collected included clinical features prior to infection, symptoms during the acute phase, hospitalization and symptom persistence after 1 and 6 months. Long COVID was defined according to CDC criteria as persistence of at least one COVID-related symptom for one or more months after diagnosis. The mean variation of FEV1 recorded 6 months after acute infection was also evaluated.

RESULTS: A total of 1102 people with CF were recruited (median age: 18 years, 520 younger than 18). The infection was symptomatic in 90.1 % of cases. During the acute phase, 8 subjects required oxygen support; 31 were hospitalized, one patient required intensive care. Complications included one thromboembolic event and two episodes of myocarditis, but no patient died. Mean variation of FEV1 after 6 months from the infection was +1.8 % (95 % CI: 1.0-2.7). Long COVID was documented in 64 subjects (5.8 %, 95 % CI: 4.5-7.4) with a variety of symptoms which were still present in 12 cases 6 months after infection (1.1 %, 95 % CI: 0.6-1.9).

CONCLUSIONS: In the omicron phase of the pandemic, COVID-19 was relatively mild and did not negatively impact pulmonary function after 6 months. Long COVID was observed at all ages, but extrapulmonary symptoms were more frequent and persistent in adults.},
}

@article {pmid40907708,
year = {2025},
author = {Tashima, R and Kuroda, T and Nobori, H and Miyagawa, S and Yamane, T and Shimba, A and Nakashima, M and Fukao, K},
title = {Ensitrelvir suppresses prolonged olfactory abnormalities derived from SARS-CoV-2 infection in hamsters.},
journal = {Antiviral research},
volume = {},
number = {},
pages = {106270},
doi = {10.1016/j.antiviral.2025.106270},
pmid = {40907708},
issn = {1872-9096},
abstract = {Ensitrelvir, an oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease inhibitor, is reportedly effective in suppressing smell disorder onset, a post-coronavirus disease 2019 (COVID-19) condition symptom. However, the pathogenesis of post-COVID-19 condition symptoms and the mechanism underlying the onset-suppressive effect of ensitrelvir are not fully understood. Here, we explored a post-COVID-19 condition model in hamsters 1 month post-SARS-CoV-2 infection and showed that ensitrelvir treatment caused early recovery of body weight, viral RNA suppression, and sense of smell improvement. In the nasal turbinates, SARS-CoV-2 was associated with significantly increased inflammatory markers, many of which were suppressed by ensitrelvir. Significant positive correlations were observed between smell testing and many inflammation-related markers in the nasal turbinates. In conclusion, our study indicates that chronic inflammation may occur in the nasal turbinates over a long period post-SARS-CoV-2 infection, leading to smell disorder onset in a hamster model. Early ensitrelvir treatment post-infection suppressed inflammation in the nasal turbinates and prevented smell disorder onset.},
}

@article {pmid40906352,
year = {2025},
author = {Tobey, M and Purvis, SJ and Daubman, BR and Isaacson, MJ and Duran, T and Johnson, G and LaPlante, JR and Armstrong, K},
title = {The Experience of Long COVID Among American Indian Individuals in Three Great Plains Communities.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {40906352},
issn = {2196-8837},
abstract = {Long COVID may impact populations differently. In July 2023, at the direction of a community advisory board, we administered a cross-sectional survey to explore attitudes and experiences of long COVID among members of three American Indian Reservation communities in the Great Plains. Just over half of the 843 respondents considered long COVID to be an important issue in their community, an attitude that was associated with younger age, identifying as male, having more than a high school education, full-time employment, living with children, and living on the Reservation. Of survey respondents who reported having had COVID-19, 40% reported ongoing symptoms at the time of the survey. Having ongoing symptoms was associated with identifying as female, living alone with children, and having had long COVID-19 symptoms during the initial infection. To explore ongoing symptoms, we performed a factor analysis that identified three symptom clusters with distinct sociodemographic associations. The results suggest that health and workforce sequelae of COVID-19 infections may present challenges for the surveyed communities and that ongoing symptoms after COVID-19 infection were common.},
}

@article {pmid40905682,
year = {2025},
author = {Gracie, NP and Aggarwal, A and Luo, R and Spicer, M and Idrees, S and Ashley, CL and Alca, S and Ison, T and Steain, MC and Patel, K and Siddiquee, R and Low, JKK and Mackay, JP and Denes, CE and Neely, GG and Faiz, A and Turville, SG and Newsome, TP},
title = {An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0043525},
doi = {10.1128/jvi.00435-25},
pmid = {40905682},
issn = {1098-5514},
abstract = {UNLABELLED: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates canonical cell entry via ACE2 and has also been implicated as an activator of a diverse range of signaling pathways. Here, we present evidence that the RGD (Arg-Gly-Asp) motif within the receptor-binding domain (RBD) of the S1 fragment of the S protein induces TGF-β cytokine expression. RGD peptides are well characterized as ligands for a subset of integrin complexes primarily containing α5 and αV subunits. In this study, we investigate the molecular basis of TGF-β pathway activation by S protein, delivered to cells as recombinant protein, in pseudotyped virus or in virally infected cells. Activation of TGF-β signaling by the S protein requires ACE2 and leads to SMAD3-dependent expression of the pro-fibrotic marker PAI-1. Utilizing pseudotyped viruses, expression of the S protein with a mutated RGD motif abolished TGF-β signaling, as did the RGD antagonist ATN-161, implicating integrin complexes in mediating this response. We show that the S protein RGD motif suppresses IFN-β expression via TGF-β, leading to a disruption in cellular antiviral defenses, consistent with TGF-β's role in immunosuppression. These findings further support the multifunctionality of S protein and provide mechanistic insights into its activity as a virulence factor during infection.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an ongoing public health challenge as a cause of acute illness and post-acute sequelae of COVID-19 (PASC, or long COVID). Our study identifies the RGD integrin-binding motif in the spike (S) protein as central to the cellular response to SARS-CoV-2, leading to the expression of the pleiotropic cytokine TGF-β and disabling of antiviral immunity. This work further supports the S protein-to-integrin complex signaling axis as a potential therapeutic target. The RGD motif might also be a valid target for treating PASC given the increasing body of evidence implicating the presence of persistent S protein in the etiology of this disease.},
}

@article {pmid40905101,
year = {2025},
author = {Lotankar, Y and Cheshire, A and Ridge, D and Chew-Graham, C and Smyth, N and Knowles, CR and Gopal, D and Kingstone, T and Dawson, S},
title = {Intersectionality and Long Covid: Understanding the Lived Experiences of Ethnic Minority Groups in the United Kingdom.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70413},
doi = {10.1111/hex.70413},
pmid = {40905101},
issn = {1369-7625},
support = {//Y.V.L. was funded by a PhD Studentship from the University of Westminster. C.C.G. is part-funded by West Midlands Applied Research Collaboration. Original data collection was funded by the National Institute for Health Research, under the Patient Benefit programme (NIHR203106)./ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/ethnology/psychology ; United Kingdom/epidemiology ; *Minority Groups/psychology/statistics & numerical data ; Middle Aged ; *Ethnicity/psychology/statistics & numerical data ; Adult ; Interviews as Topic ; Socioeconomic Factors ; Aged ; Qualitative Research ; SARS-CoV-2 ; Health Services Accessibility ; Sex Factors ; Post-Acute COVID-19 Syndrome ; Comorbidity ; },
abstract = {INTRODUCTION: Long Covid is the patient-preferred term to describe persistent symptoms experienced following an acute Covid-19 infection. The severity and unpredictable nature of long Covid symptoms can affect every aspect of an individual's life. Under-represented groups such as ethnic minorities and lower socio-economic groups are disproportionately affected by long Covid and often face challenges in accessing healthcare and additional support. This study employed an intracategorical intersectionality approach to explore how the diverse experiences of long Covid among people from ethnic minority backgrounds are influenced by complexities like gender and socio-economic factors.

METHODS: A secondary analysis of 31 semi-structured interviews with individuals with long Covid from ethnic minority backgrounds, using reflexive thematic analysis.

RESULTS: Findings are presented around the themes: (i) gender and ethnicity; (ii) socio-economic factors and illness experience; and (iii) comorbidities, disabilities and living with long Covid. Participants describe challenges in gaining support, including from health professionals, family and communities, but these challenges were gendered to a degree, with women and men describing distinctive difficulties. Financial capacity was considered important in determining the type and extent of accessible care. Support from employers also influenced participant's ability to take adequate time to recover and return to work. The interplay of comorbidities with long Covid could heighten the risk of more severe symptoms and complicate help-seeking for -and management of -long Covid.

CONCLUSION: An intracategorical intersectional exploration of lived experience is necessary to reveal the nuances in individual experiences of long Covid. Findings will be of interest to health professionals and researchers in supporting their understanding of intersectional experiences of their patients.

PATIENT PUBLIC INVOLVEMENT: The HI-COVE study was informed throughout by patient and expert advisory groups composed of individuals from ethnic minority backgrounds living with long Covid, their carers and professionals interested in this topic.},
}

Humans
Male
Female
*COVID-19/ethnology/psychology
United Kingdom/epidemiology
*Minority Groups/psychology/statistics & numerical data
Middle Aged
*Ethnicity/psychology/statistics & numerical data
Adult
Interviews as Topic
Socioeconomic Factors
Aged
Qualitative Research
SARS-CoV-2
Health Services Accessibility
Sex Factors
Post-Acute COVID-19 Syndrome
Comorbidity

@article {pmid40904575,
year = {2025},
author = {Shen, S and Zhao, X and Pei, J and Wang, B and Hou, J and Chai, R and Guo, Y and Li, F and Hao, J and Wu, Z},
title = {Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1555370},
pmid = {40904575},
issn = {1664-0640},
abstract = {Long COVID (LC) refers to a multisystem condition that persists after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). In addition to physical symptoms, the psychological impact is particularly pronounced. This review summarizes the manifestations, potential mechanisms, epidemiological characteristics, and current interventions related to psychological disorders in LC. Drawing on domestic and international literature, it highlights anxiety, depression, cognitive dysfunction, and post-traumatic stress disorder (PTSD) as the primary psychological symptoms. These symptoms may be associated with neuroinflammation, immune abnormalities, vascular dysfunction, and psychosocial stress. Although research in this area is still developing, psychotherapy, pharmacotherapy, neuromodulation, and lifestyle interventions show promise as treatment approaches. This review aims to provide insights that can inform future research on clinical treatments and psychological care for individuals with LC.},
}

@article {pmid40903751,
year = {2025},
author = {Nguyen, NN and Tissot-Dupont, H and Brouqui, P and Gautret, P},
title = {Post-COVID syndrome in symptomatic COVID-19 patients: a retrospective cohort study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1099},
pmid = {40903751},
issn = {1471-2334},
abstract = {BACKGROUND: Although post-COVID symptoms have been documented in the literature, the risk factors and time required for full recovery remain unclear. We conducted a retrospective analysis of medical records of COVID-19 patients to investigate the prevalence of symptoms after an acute episode of COVID-19 and the risk factors for persistence of symptoms.

METHODS: This retrospective cohort study analysis examined hospital records of post-COVID individuals with previously confirmed or probable SARS-CoV-2 infection and endurring symptom continuation for at least 3 months post-infection or presenting new symptoms persisting for at least 2 months. Follow-up was conducted during at least six months to access longer-term outcomes. The majority of patients received specialized examination and at least two medical examinations. Descriptive and logistic regression analysis was applied to determine the prevalence and risk factors for post-COVID syndrom.

RESULT: The mean age of the 319 patients was 47.74 ± 11.61 years, and 225 (70.1%) were female. Of the 250/319 patients for whom information on acute infection was available; fever (60.8%), smell disorder (60.8%), asthenia (60.4%) and headache (59.2%) were the most frequent symptoms. The most frequent persisting symptoms were neurological (84.6%), asthenia (80.9%) and cardiac-respiratory symptoms (67.4%). About 80-81% patients reported symptom improvement at six to twelve months of follow-up. Being male and having fever or taste disorders during the acute phase of COVID-19 were independent risk factors for the persistence of long COVID symptoms.

CONCLUSION: These results could possibly serve to identify patients at a higher risk for the persistence of long COVID symptoms and target them for reinforced therapeutic measures.},
}

@article {pmid40901355,
year = {2025},
author = {Colgan, DD and Stadler, DD and Hope, AA and Zwickey, H and Davenport, TE and Weimbs, T},
title = {Clinically Meaningful Improvements in Long COVID Symptoms Following Ketogenic Metabolic Therapy Combined with Lifestyle Interventions-A Clinical Case Report and Review of the Literature.},
journal = {Case reports in clinical medicine},
volume = {14},
number = {8},
pages = {391-410},
doi = {10.4236/crcm.2025.148052},
pmid = {40901355},
issn = {2325-7075},
abstract = {Approximately 400 million individuals globally are estimated to suffer from Long COVID, an infection-associated chronic condition that occurs after SARS-CoV-2 infection. Despite the high burden, there are no evidence-based or FDA-approved interventions to treat the condition. Given its complexity, a multicomponent approach grounded in a whole-person health model is likely required. This case report highlights clinically meaningful improvements in multiple Long COVID symptoms following a remotely-delivered, ketogenic metabolic therapy combined with group health coaching. Nutritional interventions were paired with exercises to stabilize circadian rhythms and introduce mindfulness-based practices. A review of the literature provides evidence in support of ketogenic metabolic therapy and lifestyle interventions as strategies to target proposed underlying mechanisms of Long COVID and foster stress resilience, thus reducing symptoms and improving quality of life. Findings support future research to optimize and evaluate multimodal nutritional and lifestyle interventions for Long COVID.},
}

@article {pmid40900636,
year = {2025},
author = {Pokharel, BR and Majumdar, N and Williams, F and Dickerson, A and Croy, H and Eells, JB and Didonna, A and Sriramula, S and Cook, PP and Akula, SM},
title = {SARS-CoV-2 infection of substantia nigra pars compacta induces expression of miR-330-5p at 10 days post-infection.},
journal = {The Journal of general virology},
volume = {106},
number = {9},
pages = {},
doi = {10.1099/jgv.0.002149},
pmid = {40900636},
issn = {1465-2099},
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; Mice ; *COVID-19/genetics/virology/pathology/metabolism ; Humans ; Mice, Transgenic ; *SARS-CoV-2 ; Angiotensin-Converting Enzyme 2/genetics ; *Substantia Nigra/virology/metabolism/pathology ; Microglia ; Disease Models, Animal ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been linked to several neurological symptoms in coronavirus disease 2019 (COVID-19) patients; however, the molecular mechanisms underlying virus-induced neuroinflammation are not well identified. For example, the effect of SARS-CoV-2 infection of the substantia nigra pars compacta (SNpc) of the midbrain has not been addressed, in spite of its importance in dopaminergic signalling and neurodegenerative abnormalities. The purpose of this study was to understand the SARS-CoV-2-induced inflammatory response in the SNpc region of the brain. We inoculated (intranasally) transgenic mice expressing human ACE2 under control of the human keratin 18 promoter (K18-hACE-2 mice) with a 4×10[3] TCID50 (mild) dose of SARS-CoV-2. Ten days post-inoculation, SARS-CoV-2 was detected in the SNpc of mice, along with increased levels of IL-1β, B1R and ADAM17, and reduced microglial/macrophage occurrence. miR-330-5p expression was significantly reduced in virus-positive SNpc tissue. Luciferase reporter assays supported ADAM17 as a direct target of miR-330-5p. There was no significant difference in miR-330-5p expression levels in the experimental autoimmune encephalomyelitis mice compared to control mice, demonstrating a crucial role for SARS-CoV-2-induced miR-330-5p in brain pathology. Our study uncovers for the first time that SARS-CoV-2 can invade the SNpc and downregulate miR-330-5p expression levels, causing an enhanced ADAM17 expression and possible neuroinflammatory signalling. The results implicate miR-330-5p as a prospective therapeutic target for alleviating midbrain inflammation associated with SARS-CoV-2 infection.},
}

*MicroRNAs/genetics/metabolism
Animals
Mice
*COVID-19/genetics/virology/pathology/metabolism
Humans
Mice, Transgenic
*SARS-CoV-2
Angiotensin-Converting Enzyme 2/genetics
*Substantia Nigra/virology/metabolism/pathology
Microglia
Disease Models, Animal

@article {pmid40900297,
year = {2025},
author = {Ahmad, A and Janjua, NZ and Lix, LM and Warda, N and Fung, DLX and Bhéreur, A and Bobos, P and Carazo, S and Décary, S and Goulding, S and Graves, L and Groot, G and Gross, DP and Manhas, KP and McNaughton, CD and Rahme, E and Sander, B and Sbihi, H and Verma, AA and Quinn, KL},
title = {A national atlas to improve the study of Canadians living with long COVID (post-COVID-19 condition).},
journal = {Canadian journal of public health = Revue canadienne de sante publique},
volume = {},
number = {},
pages = {},
pmid = {40900297},
issn = {1920-7476},
support = {492634/CAPMC/CIHR/Canada ; },
abstract = {OBJECTIVES: To develop a national atlas of (1) Canadian cohorts studying or with the potential to study adults living with long COVID (LC) and (2) harmonize provincial and territorial administrative datasets to facilitate the creation of validated case-ascertainment algorithms and foster national collaboration on LC research.

METHODS: We conducted a multifaceted environmental scan that included a comprehensive literature search and a survey of members of Canada's national LC research network between August 21, 2023, and November 10, 2023. We identified provincial and territorial cohorts, including those that were linkable to administrative data and common data elements among administrative datasets.

RESULTS: We included 19 Canadian cohorts from five provinces (Alberta, British Columbia, Manitoba, Ontario, and Québec) containing data on over 580,000 adults. The majority of the cohorts measured sociodemographic data (e.g., age, sex) and measures of healthcare use, whereas equity-related measures such as gender, ethnicity, and race were limited. There was wide variability in the definitions of LC used across all cohorts. Comparable population-level administrative data are currently available in Alberta, British Columbia, Manitoba, Ontario, Québec, New Brunswick, Newfoundland and Labrador, Nova Scotia, and Saskatchewan.

CONCLUSION: Canada has a rich repository of LC datasets that are limited by variable definitions of LC and inadequate equity-related measures such as gender, ethnicity, and race. Standardization and diversification of these measures will facilitate efforts to study healthcare use and develop health policy to improve the care of Canadian adults living with LC at a population level.},
}

@article {pmid40898520,
year = {2025},
author = {Bai, W and Li, F},
title = {Regulation of m7G methylation in long COVID: Expression profiles and early predictive value of key genes.},
journal = {Medicine},
volume = {104},
number = {35},
pages = {e44209},
doi = {10.1097/MD.0000000000044209},
pmid = {40898520},
issn = {1536-5964},
support = {2023D01C140//Xinjiang Uygur Autonomous Region Natural Science Foundation/ ; },
mesh = {Humans ; *COVID-19/genetics ; Gene Expression Profiling ; *Guanosine/analogs & derivatives/metabolism ; SARS-CoV-2 ; *DNA Methylation ; Protein Interaction Maps ; Transcriptome ; },
abstract = {Long COVID (LC) poses ongoing public health challenges due to its persistent symptoms following severe acute respiratory syndrome coronavirus 2 infection. Early identification of at-risk individuals remains difficult, and molecular biomarkers are urgently needed. This study aimed to explore the role of N7-methylguanosine (m7G) methylation-related regulatory genes in LC pathogenesis and to develop a predictive model for early detection. Gene expression profiles of LC patients were obtained from the GEO database (GSE224615), and differentially expressed genes (DEGs) were identified. These DEGs were intersected with m7G regulatory genes to identify LC-specific candidates. A protein-protein interaction network was constructed to identify hub genes, and enrichment analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were performed to investigate the biological relevance of the identified genes. Immune cell infiltration analyses were conducted to explore the immunological features associated with candidate genes. Findings were validated using an external dataset (GSE217948). A clinical prediction model was constructed using Least absolute shrinkage and selection operator regression followed by logistic regression, and evaluated via receiver operating characteristic curve, calibration, and decision curve analysis. A total of 65 DEGs were identified in LC patients, comprising 44 up-regulated and 21 down-regulated genes. Thirty genes overlapped with the m7G regulatory gene set. Functional enrichment revealed significant involvement in pathways such as FceRI-mediated NF-κB activation and platelet aggregation. Correlation analysis showed that several m7G-related genes were associated with altered immune cell infiltration patterns. The external dataset confirmed the reproducibility of gene expression trends. Seven core genes were ultimately selected to build the predictive model, which demonstrated robust performance in distinguishing LC patients from controls. This study highlights the importance of m7G methylation in LC pathogenesis and uncovers novel immune-related mechanisms underlying its persistence. The predictive model based on m7G-related markers provides a promising tool for early LC identification and may inform future diagnostic and therapeutic strategies.},
}

Humans
*COVID-19/genetics
Gene Expression Profiling
*Guanosine/analogs & derivatives/metabolism
SARS-CoV-2
*DNA Methylation
Protein Interaction Maps
Transcriptome

@article {pmid40897497,
year = {2025},
author = {McDuff, K and Bhéreur, A and Kadakia, Z and Corrales-Medina, VF and Gross, DP and Janaudis-Ferreira, T and Lam, G and Naik, H and Paterson, TSE and Sanchez-Ramirez, DC and Sasseville, M and Sekar, A and Vohra, S and Bayley, M and Birch, S and Busse, JW and Cameron, JI and Kaup, C and Cheung, A and Churchill, K and Edgell, H and Goulding, S and Hamilton, C and Jaglal, S and Kumar, P and Levin, A and Munblit, D and Naye, F and O'Hara, M and Plaismond, J and Rutledge, M and Supper, JW and Quinn, K and Wasilewski, MB and Wilkins, A and O'Brien, KK},
title = {Establishing a framework of measurement for use in Long COVID research and practice: protocol for a scoping review involving evidence review and consultation.},
journal = {BMJ open},
volume = {15},
number = {9},
pages = {e094497},
doi = {10.1136/bmjopen-2024-094497},
pmid = {40897497},
issn = {2044-6055},
abstract = {INTRODUCTION: Our aim is to develop a Framework of Measurement for people living with Long COVID and their caregivers for use in Long COVID research and clinical practice. Specifically, we will characterise evidence pertaining to outcome measurement and identify implementation considerations for use of outcome measures among adults and children living with Long COVID and their caregivers.

METHODS AND ANALYSIS: We will conduct a scoping study involving: (1) an evidence review and (2) a two-phased consultation, using methodological steps outlined by the Arksey and O'Malley Framework and Joanna Briggs Institute. We will answer the following question: What is known about outcome measures used to describe, evaluate or predict health outcomes among adults and children living with Long COVID and their caregivers?

EVIDENCE REVIEW: we will review peer review published and grey literature to identify existing outcome measures and their reported measurement properties with people living with Long COVID and their caregivers. We will search databases including MEDLINE, Embase, CINAHL, PsycINFO and Scopus for articles published since 2020. Two authors will independently review titles and abstracts, followed by full text to select articles that discuss or use outcome measures for Long COVID health outcomes, pertain to adults or children living with Long COVID and/or their caregivers and are based in research or clinical settings. We will extract data including article characteristics, terminology and definition of Long COVID, health outcomes assessed, characteristics of outcome measures, measurement properties and implementation considerations. We will collate and summarise data to establish a preliminary Framework of Measurement. Consultation phase 1: we will conduct an environmental scan involving a cross-sectional web-based questionnaire among individuals with experience using or completing outcome measures for Long COVID, to identify outcome measures not found in the evidence review and explore implementation considerations for outcome measurement in the context of Long COVID. Consultation phase 2: we will conduct focus groups to review the preliminary Framework of Measurement and to highlight implementation considerations for outcome measurement in Long COVID. We will analyse questionnaire and focus group data using descriptive and content analytical approaches. We will refine the Framework of Measurement based on the focus group consultation using community-engaged approaches with the research team.

ETHICS AND DISSEMINATION: Protocol approved by the University of Toronto Health Sciences Research Ethics Board (protocol #46503) for the consultation phases of the study. Outcomes will include a Framework of Measurement, to enhance measurement of health outcomes in Long COVID research and clinical practice. Knowledge translation will also occur in the form of publications and presentations.},
}

@article {pmid40895196,
year = {2025},
author = {Eltoum, AI and Begum, R and Gold, LS and Patel, PB and Andrews, JS},
title = {Exploring the Associations between Self-Reported Sleep Disturbance and Cognitive Impairment among Survivors of COVID-19 Hospitalization.},
journal = {Mental health science},
volume = {3},
number = {3},
pages = {},
doi = {10.1002/mhs2.70027},
pmid = {40895196},
issn = {2642-3588},
abstract = {STUDY OBJECTIVES: Cognitive impairment following COVID-19 infection is common and risk factors remain poorly understood. Sleep disturbance increases risk of cognitive impairment in the general population, and sleep disturbance is common after COVID-19. While prior literature has extensively explored the relationship between sleep and cognition, few studies have addressed the temporality of this association and how one may contribute to the other over time. This study assessed whether new sleep disturbance at 1-month is associated with risk of cognitive impairment at 6-months after COVID-19 hospitalization.

METHODS: English-speaking adults aged ≥18 years at the University of Washington Medical Center who survived to 1-month post-COVID-19 hospitalization were enrolled. Self-reported sleep disturbance, cognitive function, cognitive abilities, and fatigue severity at 1- and 6-months after discharge were assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS[®]) short forms. Linear and logistic regression models analyzed associations of new sleep disturbance at 1-month with cognitive function, cognitive abilities, and fatigue severity outcomes at 6-months.

RESULTS: Participants (n=120) had mean age of 56.5±15.7 years, and 35% developed new sleep disturbance at 1-month. Among those with versus without new sleep disturbance at 1-month, 74% versus 40%, 76% versus 37%, and 64% versus 50% developed significant worsening in cognitive function, cognitive abilities, and fatigue severity at 6 months, respectively.

CONCLUSIONS: In this single-center observational cohort, new sleep disturbance at 1-month post-COVID-19 hospitalization was associated with subsequent significant worsening in cognitive function, cognitive abilities, and fatigue severity at 6-months. Thus, new sleep disturbance may be a risk factor for persistent neurocognitive impairment after COVID-19. Additional studies should validate these relationships and examine whether improving sleep quality may reduce the risk of cognitive impairment in these patients.},
}

@article {pmid40894595,
year = {2025},
author = {Kwissa, M and Mathayan, M and Salunkhe, SS and Bakthavachalam, V and Ye, Z and Sanborn, MA and Condo, S and Upadhye, A and Nemakal, A and Richner, JM and Basu, S and Novak, RM and Jacobson, JR and Ganesh, BB and Cerda, M and Utz, PJ and Krishnan, JA and Prabhakar, BS and Rehman, J},
title = {Persistent Immune Dysregulation during Post-Acute Sequelae of COVID-19 is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.18.670908},
pmid = {40894595},
issn = {2692-8205},
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome or "Long COVID" represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of PASC, but the extent of PASC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed PASC. Compared to convalescent, PASC participants with a broad range of PASC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the PASC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis, we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa-associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in PASC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in PASC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity.},
}

@article {pmid40894471,
year = {2025},
author = {Dias Rodrigues, G and Fazan, R and Montano, N},
title = {Editorial: Updates on cardiovascular variability: underlying mechanisms and non-pharmacological therapeutic targets.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1670996},
doi = {10.3389/fcvm.2025.1670996},
pmid = {40894471},
issn = {2297-055X},
}

@article {pmid40893436,
year = {2025},
author = {Zeng, J and Jia, X},
title = {Quantifying compatibility mechanisms in traditional Chinese medicine with interpretable graph neural networks.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {8},
pages = {101342},
doi = {10.1016/j.jpha.2025.101342},
pmid = {40893436},
issn = {2214-0883},
abstract = {Traditional Chinese medicine (TCM) features complex compatibility mechanisms involving multi-component, multi-target, and multi-pathway interactions. This study presents an interpretable graph artificial intelligence (GraphAI) framework to quantify such mechanisms in Chinese herbal formulas (CHFs). A multidimensional TCM knowledge graph (TCM-MKG; https://zenodo.org/records/13763953) was constructed, integrating seven standardized modules: TCM terminology, Chinese patent medicines (CPMs), Chinese herbal pieces (CHPs), pharmacognostic origins (POs), chemical compounds, biological targets, and diseases. A neighbor-diffusion strategy was used to address the sparsity of compound-target associations, increasing target coverage from 12.0% to 98.7%. Graph neural networks (GNNs) with attention mechanisms were applied to 6,080 CHFs, modeled as graphs with CHPs as nodes. To embed domain-specific semantics, virtual nodes medicinal properties, i.e., therapeutic nature, flavor, and meridian tropism, were introduced, enabling interpretable modeling of inter-CHP relationships. The model quantitatively captured classical compatibility roles such as "monarch-minister-assistant-guide," and uncovered TCM etiological types derived from diagnostic and efficacy patterns. Model validation using 215 CHFs used for coronavirus disease 2019 (COVID-19) management highlighted Radix Astragali-Rhizoma Phragmitis as a high-attention herb pair. Mass spectrometry (MS) and target prediction identified three active compounds, i.e., methylinissolin-3-O-glucoside, corydalin, and pingbeinine, which converge on pathways such as neuroactive ligand-receptor interaction, xenobiotic response, and neuronal function, supporting their neuroimmune and detoxification potential. Given their high safety and dietary compatibility, this herb pair may offer therapeutic value for managing long COVID-19. All data and code are openly available (https://github.com/ZENGJingqi/GraphAI-for-TCM), providing a scalable and interpretable platform for TCM mechanism research and discovery of bioactive herbal constituents.},
}

@article {pmid40892700,
year = {2025},
author = {Jothi, S and Insel, M and Claessen, G and Kubba, S and Howden, EJ and Ruiz-Carmona, S and Levine, T and Rischard, FP},
title = {Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.},
journal = {Physiological reports},
volume = {13},
number = {17},
pages = {e70535},
doi = {10.14814/phy2.70535},
pmid = {40892700},
issn = {2051-817X},
mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/metabolism ; *COVID-19/physiopathology/complications ; Male ; Female ; Oxygen Consumption ; Adult ; Middle Aged ; Muscle, Skeletal/metabolism/physiopathology ; *Exercise Tolerance ; Exercise Test ; *Exercise/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Post-acute sequelae of SARS-CoV-2 (PASC or "long COVID") and chronic fatigue syndrome/myalgic encephalitis (CFS/ME) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 PASC patients, 11 CFS/ME patients, and 11 controls. We evaluated the contributions of alveolar ventilation (V̇a), lung diffusion capacity (DL), cardiac output (Q̇), skeletal muscle diffusion capacity (DM), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (Vmax) to peak oxygen consumption (V̇O2peak). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V̇O2peak. V̇O2peak was significantly reduced in both PASC and CFS/ME compared to controls. Skeletal muscle O2 diffusion (DM) was the most impaired parameter in both patient groups (p = 0.01). Correcting DM alone improved V̇O2 by 66% in PASC (p = 0.008) and 34.7% in CFS/ME (p = 0.06), suggesting a dominant role for peripheral O2 extraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (DM) is a shared mechanism of exercise intolerance in PASC and CFS/ME and may represent a therapeutic target. However, our findings are limited by small sample size.},
}

Humans
*Fatigue Syndrome, Chronic/physiopathology/metabolism
*COVID-19/physiopathology/complications
Male
Female
Oxygen Consumption
Adult
Middle Aged
Muscle, Skeletal/metabolism/physiopathology
*Exercise Tolerance
Exercise Test
*Exercise/physiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid40889165,
year = {2025},
author = {Gomez-Bravo, R and León-Herrera, S and Guisado-Clavero, M and Gefaell, I and Wostmann, X and Wössner, N and Vinker, S and Vassallo La Ferla, F and Kırkoç Üçüncü, E and Tsigarovski, G and Torzsa, P and Suija, K and Stepanović, A and Sentker, T and Segernäs, A and Seifert, B and Sánchez-Castro, M and Schneider, JG and Repovská, A and Petrazzuoli, F and Petek, D and Perjes, A and Parodi López, N and Neves, AL and Nessler, K and Muris, J and Mortsiefer, A and Moreels, S and Meister, T and Mäntyselkä, P and Murauskienė, L and Lingner, H and Krztoń-Królewiecka, A and Kostic, M and Çimen Korkmaz, B and Knezevic, S and Kazakos, S and Karathanos, V and Shushman, I and Ilkov, O and Hoffmann, K and Heleno, B and Hanževački, M and Gjorgjievski, D and Frese, T and Fournier, M and Fitzgerald, L and Feldmane, S and Dotsenko, M and Domeyer, PR and Croucher, D and Cerny, V and Burgers, JS and Brutskaya-Stempkovskaya, E and Busneag, CI and Buono, N and Bensemmane, S and Bayen, S and Bakola, M and Assenova, R and Adler, L and Ares-Blanco, S and Astier Peña, MP},
title = {Towards consensus: The need for standardised definitions in Long (post) COVID care in 34 European countries.},
journal = {The European journal of general practice},
volume = {31},
number = {1},
pages = {2535618},
doi = {10.1080/13814788.2025.2535618},
pmid = {40889165},
issn = {1751-1402},
mesh = {Humans ; *COVID-19/therapy/diagnosis/epidemiology ; Europe/epidemiology ; Retrospective Studies ; Consensus ; SARS-CoV-2 ; *Terminology as Topic ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: The COVID-19 pandemic has significantly impacted global healthcare systems, leading to challenges in managing Long COVID. Variations in definitions and diagnostic criteria across Europe hinder recognition and treatment efforts. This study aims to analyse and compare the definitions of Long COVID used in 34 European countries.

METHODS: A retrospective descriptive study was conducted involving key informants from 34 European countries, utilising an online questionnaire to gather data on Long COVID definitions. Quantitative and qualitative analyses were employed to assess the variability of definitions and challenges in managing Long COVID.

RESULTS: The study found significant variation in Long COVID definitions among the participating countries; the most frequent definition was the other definition (n: 17, 50.0%), followed by the World Health Organisation's definition (n: 16, 47.0%) and the CDC definition (n: 11, 32.3%). Half of the countries reported using multiple definitions simultaneously, indicating a lack of standardisation. Qualitative analyses highlighted challenges such as difficulties in standardising terminology, variability in clinical criteria, and issues with implementing diagnostic codes.

CONCLUSION: The findings underscore the need for a unified, yet adaptable, definition of Long COVID. Such a definition would support general practitioners (GPs) by simplifying diagnostic processes, improving continuity of care, and facilitating equitable patient access to multidisciplinary resources. The current lack of consensus complicates patient care, data collection, and resource allocation, impacting health policy development. Future efforts should focus on achieving agreement on definitions to ensure equitable treatment and effective healthcare responses to Long COVID.},
}

Humans
*COVID-19/therapy/diagnosis/epidemiology
Europe/epidemiology
Retrospective Studies
Consensus
SARS-CoV-2
*Terminology as Topic
Surveys and Questionnaires

@article {pmid40888500,
year = {2025},
author = {Fain, MJ and Horne, BD and Horwitz, LI and Thaweethai, T and Greene, M and Hornig, M and Orkaby, AR and Rosen, C and Ritchie, CS and Ashktorab, H and Blachman, N and Brim, H and Emerson, S and Erdmann, N and Erlandson, KM and de Erausquin, G and Fong, T and Geng, LN and Gordon, HS and Gully, JR and Hadlock, J and Han, J and Huang, W and Jagannathan, P and Kelly, JD and Klein, JD and Krishnan, JA and Levitan, EB and McComsey, GA and McDonald, D and Montgomery, AP and O'Brien, L and Ofotokun, I and Patterson, TF and Peluso, MJ and Pemu, P and Perlowski, A and Reiman, EM and Sanon, M and Seshadri, S and Shellito, J and Sherif, ZA and Shikuma, C and Singer, NG and Singh, U and Trinity, JD and Wisnivesky, J and Witvliet, MG and Foulkes, A and Nikolich, JŽ and , },
title = {Age-Related Changes in the Clinical Picture of Long COVID.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70043},
pmid = {40888500},
issn = {1532-5415},
support = {//William Randolph Hearst Foundations/ ; //O. Wayne Rollins Foundation/ ; UM1TR004409/TR/NCATS NIH HHS/United States ; UM1TR004528/TR/NCATS NIH HHS/United States ; P30AG066546/AG/NIA NIH HHS/United States ; P30AG072980/AG/NIA NIH HHS/United States ; R56AG074467/AG/NIA NIH HHS/United States ; OT2HL161841/HL/NHLBI NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID.

METHODS: We analyzed community-dwelling participants ≥ 60 years old (2662 with prior infection, 461 controls) compared to participants 18-59 years (7549 infected, 728 controls) in the Researching COVID to Enhance Recovery adult (RECOVER-Adult) cohort ≥ 135 days post-onset.

RESULTS: Compared to the Age 18-39 group, the adjusted odds of LCRI ≥ 12 were higher for the Age 40-49 group (odds ratio [OR] = 1.40, 95% confidence intervals [CI] = 1.21-1.61, p < 0.001) and 50-59 group (OR = 1.31, CI = 1.14-1.51, p < 0.001), similar for the Age 60-69 group (OR = 1.09, CI = 0.93-1.27, p = 0.299), and lower for the ≥ 70 group (OR = 0.68, CI = 0.54-0.85, p < 0.001). Participants ≥ 70 years had smaller adjusted differences between infected and uninfected symptom prevalence rates than those aged 18-39 for the following symptoms: hearing loss, fatigue, pain (including joint, back, chest pain and headache), post-exertional malaise, sleep disturbance, hair loss, palpitations, and sexual desire/capacity, making these symptoms less discriminating for Long COVID in older adults than in younger. Symptom clustering, as described in Thaweethai et al. (JAMA 2023) also exhibited age-related shifts: clusters 1 (anosmia and ageusia) and 2 (gastrointestinal, chronic cough and palpitations, without anosmia, ageusia or brain fog) were more likely, and clusters 3 (brain fog, but no loss of smell or taste) and 4 (a mix of symptoms) less likely to be found in older adults (relative risk ratios for clusters 3-4 ranging from 0.10-0.34, p < 0.001 vs. 18-39 year-olds).

CONCLUSIONS: Within the limits of this observational study, we conclude that in community-dwelling older adults, aging alters the prevalence and pattern of reported Long COVID.},
}

@article {pmid40887959,
year = {2025},
author = {Parums, DV},
title = {Editorial: Dormant Cancer Cells, Cancer Progression, and Post-Acute Sequelae of COVID-19 and Influenza.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {31},
number = {},
pages = {e951178},
doi = {10.12659/MSM.951178},
pmid = {40887959},
issn = {1643-3750},
mesh = {*COVID-19/complications/pathology ; Humans ; *Influenza, Human/complications/pathology ; Animals ; SARS-CoV-2 ; *Neoplasms/pathology/virology ; Disease Progression ; Mice ; Post-Acute COVID-19 Syndrome ; },
abstract = {Since the COVID-19 pandemic, vaccine uptake has fallen, and awareness of the long-term consequences of respiratory virus infections, particularly long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has also lost momentum. After a decade of declining mortality rates from cancer in the US, from 2020, registered age-standardized cancer-related deaths and mortality increased for all cancers. Cancer cell 'dormancy' results from an equilibrium between tumor cell division and apoptosis, and provides an explanation for relapse and metastasis that can occur months, years, or decades after treatment. In July 2025, findings from a study in mice infected with influenza and SARS-CoV-2 showed the rapid loss of the pro-dormancy phenotype in breast carcinoma cells in the lung, and expansion of metastatic carcinoma cells within weeks. Animal model findings support findings in cancer survivors that SARS-CoV-2 infection was significantly associated with an increased risk of lung metastasis and cancer-related mortality. This Editorial aims to highlight findings from real-world population studies on the association between COVID-19 and cancer and new experimental findings for how SARS-CoV-2, influenza, and possibly other respiratory viruses may 'awaken' dormant cancer cells.},
}

*COVID-19/complications/pathology
Humans
*Influenza, Human/complications/pathology
Animals
SARS-CoV-2
*Neoplasms/pathology/virology
Disease Progression
Mice
Post-Acute COVID-19 Syndrome

@article {pmid40887815,
year = {2025},
author = {Chaichana, U and Man, KKC and Ju, C and Makaronidis, J and Wei, L},
title = {Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf429},
pmid = {40887815},
issn = {1537-6591},
abstract = {BACKGROUND: A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post-COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.

OBJECTIVES: To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection.

DESIGN: A retrospective cohort study using a sequential target trial emulation framework.

DATA SOURCES: The United Kingdom primary care data from the Clinical Practice Research Datalink Aurum database from March 2020 to July 2023.

PARTICIPANTS: Adults with overweight or obesity (body mass index ≥ 25 kg/m²) and a record of severe acute respiratory syndrome coronavirus 2 infection were included. Exclusions included metformin use in the prior year or metformin contraindications.

MEASUREMENTS: The outcome was PCC, defined by a PCC diagnostic code or at least 1 World Health Organization-listed symptoms between 90 and 365 days after diagnosis, with no prior history of the symptom within 180 days before infection. The pooled hazard ratio and risk difference for the incidence of PCC were adjust for baseline characteristics.

RESULTS: Among 624 308 patients, 2976 initiated metformin within 90 days of COVID-19 diagnosis. The 1-year risk difference for PCC in the intention-to-treat analysis was -12.58% (hazard ratio 0.36; 95% CI, 0.32-0.41), with consistent results in subgroup analyses.

LIMITATIONS: Findings may not apply to individuals with a normal body mass index.

CONCLUSIONS: Early metformin treatment in overweight or obese individuals may reduce PCC risk. Further research is needed to confirm causality and clarify metformin's role in PCC management.},
}

@article {pmid40887598,
year = {2025},
author = {Klein, DO and Wilmes, N and Waardenburg, SF and Bonsel, GJ and Birnie, E and Wintjens, MS and Heemskerk, SC and Janssen, EB and Ghossein-Doha, C and Warlé, MC and Jacobs, LM and Hemmen, B and Verbunt, JA and van Bussel, BC and van Santen, S and Kietselaer, BL and Jansen, G and Asselbergs, FW and Linschoten, M and Haagsma, JA and van Kuijk, SMJ and , },
title = {Development and internal validation of a prediction model for post-COVID-19 condition 2 years after infection-results of the CORFU study.},
journal = {Diagnostic and prognostic research},
volume = {9},
number = {1},
pages = {18},
pmid = {40887598},
issn = {2397-7523},
support = {2020B006 CAPACITY//Dutch Heart Foundation/ ; 2020B006 CAPACITY//Dutch Heart Foundation/ ; 10430102110006 DEFENCE//The Netherlands Organization for Health Research and Development (ZonMW)/ ; 10430102110006 DEFENCE//The Netherlands Organization for Health Research and Development (ZonMW)/ ; },
abstract = {BACKGROUND: A subset of COVID-19 patients develops post-COVID-19 condition (PCC). This condition results in disability in numerous areas of patients' lives and a reduced health-related quality of life, with societal impact including work absences and increased healthcare utilization. There is a scarcity of models predicting PCC, especially those considering the severity of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and incorporating long-term follow-up data. Therefore, we developed and internally validated a prediction model for PCC 2 years after SARS-CoV-2 infection in a cohort of COVID-19 patients.

METHODS: Data from the CORona Follow-Up (CORFU) study were used. This research initiative integrated data from multiple Dutch COVID-19 cohort studies. We utilized 2-year follow-up data collected via the questionnaires between October 1st of 2021 and December 31st of 2022. Participants were former COVID-19 patients, approximately 2-year post-SARS-CoV-2 infection. Candidate predictors were selected based on literature and availability across cohorts. The outcome of interest was the prevalence of PCC at 2 years after the initial infection. Logistic regression with backward stepwise elimination identified significant predictors such as sex, BMI and initial disease severity. The model was internally validated using bootstrapping. Model performance was quantified as model fit, discrimination and calibration.

RESULTS: In total 904 former COVID-19 patients were included in the analysis. The cohort included 146 (16.2%) non-hospitalized patients, 511 (56.5%) ward admitted patients, and 247 (27.3%) intensive care unit (ICU) admitted patients. Of all participants, 551 (61.0%) participants suffered from PCC. We included 20 candidate predictors in the multivariable analysis. The final model, after backward elimination, identified sex, body mass index (BMI), ward admission, ICU admission, and comorbidities such as arrhythmia, asthma, angina pectoris, previous stroke, hernia, osteoarthritis, and rheumatoid arthritis as predictors of post-COVID-19 condition. Nagelkerke's R-squared value for the model was 0.19. The optimism-adjusted AUC was 71.2%, and calibration was good across predicted probabilities.

CONCLUSIONS: This internally validated prediction model demonstrated moderate discriminative ability to predict PCC 2 years after COVID-19 based on sex, BMI, initial disease severity, and a collection of comorbidities.},
}

@article {pmid40886878,
year = {2025},
author = {do Nascimento, KF and Alchieri, EF and Sanson, CS and Andrade Cavalli, ME and Moreira Pena, YA and Okumura Tioda, IS and de Oliveira, LE and Arend, J and Duarte, MMMF and Paniz, C and Oliveira, MS and Furian, AF and Freire Royes, LF and Fighera, MR},
title = {Neuroinflammation in long COVID: the role of the Val16Ala polymorphism of SOD2 and cognitive impairment.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2025.08.047},
pmid = {40886878},
issn = {1873-7544},
abstract = {Long COVID (LC) includes persistent behavioral and cognitive deficits, impacting quality of life. Neuroinflammation plays a key role in these alterations, with genetic factors influencing susceptibility. The MnSOD Val16Ala SNP is associated with neuroinflammation and cognitive dysfunction, but its role in LC remains unclear. This study investigated the relationship between the SOD2 Val16Ala polymorphism and neurocognitive alterations in young adults post-SARS-CoV-2 infection. Neurocognitive performance was assessed using the Neupsilin test in individuals with and without prior COVID-19. Blood samples were collected for the quantification of cytokines (IL-1, IL-6, TNF-α, and IFN-γ) and for the genotyping of the SOD2 Val16Ala polymorphism. The COVID-19 group showed worse cognitive performance and higher cytokine levels than controls, particularly in memory and executive function. Val allele carriers (Val/Ala and Val/Val) exhibited increased pro-inflammatory cytokine levels compared to Ala/Ala carriers. These findings suggest a potential interaction between genetic susceptibility and inflammatory response in post-COVID neurocognitive alterations. Young adults post-COVID-19 presented an exacerbated neuroinflammatory response, likely influencing cognition. The presence of the Val allele was associated with greater susceptibility to inflammatory events, suggesting a genetic component in LC-related neurological dysfunction. These results reinforce the role of neuroinflammation in LC and highlight the importance of genetic factors in determining cognitive outcomes. Understanding these mechanisms may help identify individuals at higher risk and support future therapeutic strategies.},
}

@article {pmid40885518,
year = {2025},
author = {Fernández-de-Las-Peñas, C and Ruiz-Ruigómez, M and Esparcia-Pinedo, L and Colom-Fernández, B and Cava-Valenciano, F and Torres-Macho, J and Arrieta-Ortubay, E and Akasbi-Moltalvo, M and Lumbreras-Bermejo, C and Arendt-Nielsen, L and Franco-Moreno, DMA},
title = {Classical Pathway Persistent Complement Activation is Associated with Specific Symptoms in Individuals with Post-COVID-19 Condition: A Case-Control Study.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108032},
doi = {10.1016/j.ijid.2025.108032},
pmid = {40885518},
issn = {1878-3511},
abstract = {OBJECTIVE: The complement system is a crucial part of the immune system. The role of complement activation in post-COVID-19 condition is still not conclusive. We present a case-control study investigating long-lasting complement hyperactivation in COVID-19 survivors with/without post-COVID-19 condition.

METHODS: A case-control (2:1 design) study was performed. Concentration levels of four proteins from classical complement pathway (C3,C4,C5,C7) as well as total hemolitycal complement (CH50) activity were obtained from blood samples in group of survivors with post-COVID-19 condition and in a comparison group of survivors without post-COVID-19 condition matched by age, sex, and vaccination status. Post-COVID-19 condition was defined when individuals self-reported at least one of these post-COVID symptoms: fatigue, arthralgia, myalgia, memory problems, newly onset headache, or palpitations.

RESULTS: Fifty-seven (56.1% women, age: 46.5, SD: 9.0 years) survivors with post-COVID-19 condition and 27 (55.5% women, age: 46.5, SD: 11.5 years) survivors without post-COVID-19 condition were evaluated 1.7 (SD 1.2) and 2.0 (SD 1.7) years after SARS-CoV-2 infection, respectively. Overall, the results did not reveal differences in complement protein levels and CH50 activity between survivors with or without post-COVID-19 condition. Patients reporting post-COVID fatigue exhibited lower C3 levels (P=0.025) than those without reporting post-COVID fatigue whereas survivors with post-COVID dyspnea reported lower levels of C3 (P=0.001), C5 (P=0.015) and C7 (P=0.030) proteins than those survivors without post-COVID dyspnea.

CONCLUSION: This explorative case-control study did not observe overall complement activation from classical pathway in survivors with post-COVID-19 condition up to two years after. Some complement proteins were elevated in individuals with specific post-COVID symptoms, e.g., fatigue or dyspnea.},
}

@article {pmid40884498,
year = {2025},
author = {Edwards, DL and Feldstein, LR and Dalton, AF and Ford, ND and Saydah, SH},
title = {Prevalence of symptoms associated with Long COVID among adolescents in the United States, Summer 2022.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf454},
pmid = {40884498},
issn = {1537-6613},
abstract = {PURPOSE: Limited information is known about Long COVID among adolescents. This study will compare the risks associated with symptoms among adolescents who tested positive, were tested but never tested positive, and who were never tested for SARS-CoV-2 infection.

METHODS: Porter Novelli survey data were collected from adolescents (12-17 years) from May 31 - July 6, 2022. Respondents self-reported their SARS-CoV-2 test results and were classified accordingly by test status. Wald's chi-squared tests were used to determine whether demographic factors and characteristics related to symptoms differed by test status. Multivariable logistic regression models were used to estimate the odds of reporting (1) symptoms lasting four weeks or longer and (2) symptoms lasting three or more months by test status and SARS-CoV-2 variant period.

RESULTS: Data were collected from 784 respondents: 264 (34%) tested positive, 291 (37%) never tested positive, and 229 (29%) were never tested for SARS-CoV-2 infection. At least one symptom lasting four weeks or longer were reported by 41% of the positive respondents, compared to 12% of negative respondents and 11% of never tested respondents (p<0.05). The odds of reporting at least one symptom lasting four or more weeks did not vary by SARS-CoV-2 variant period. Adolescents who tested positive had increased odds of any neurological symptom lasting three or more months compared to negative adolescents.

DISCUSSION: Our results demonstrate adolescents who tested positive for SARS-CoV-2 were more likely to report at least one symptom lasting for at least four weeks. However, most of these symptoms appeared to have resolved within three months.},
}

@article {pmid40884088,
year = {2025},
author = {Mak, WA and Wapperom, D and Redel, AL and Koeleman, JGM and Smit, PW and Lam-Tse, WK and van der Poll, T and Chen, HJ and den Dunnen, J and Braunstahl, GJ and Ong, DSY},
title = {Seasonal Coronavirus-Induced Immunological Imprinting and Previous Herpesvirus Infections in Patients With Long COVID.},
journal = {Journal of medical virology},
volume = {97},
number = {9},
pages = {e70582},
doi = {10.1002/jmv.70582},
pmid = {40884088},
issn = {1096-9071},
support = {//The study was supported by the Franciscus Hospital, Rotterdam, the Netherlands./ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/immunology/virology/complications ; Antibodies, Viral/blood/immunology ; Middle Aged ; Immunoglobulin G/blood/immunology ; Immunoglobulin M/blood ; *SARS-CoV-2/immunology ; Adult ; Aged ; *Herpesviridae Infections/immunology/virology/complications ; Immunoglobulin A/blood ; Seasons ; Spike Glycoprotein, Coronavirus/immunology ; Herpesviridae/immunology ; },
abstract = {Long COVID (LC) is a post-acute infection syndrome affecting 5%-10% of individuals infected by SARS-CoV-2. Here, we aimed to study SARS-CoV-2 humoral immunity, immunological imprinting by endemic coronaviruses, and previous herpesvirus infections in LC. We included 47 LC patients and 41 controls who fully recovered from COVID-19. We assessed IgG, IgA, and IgM antibody levels against SARS-CoV-2, seasonal coronaviruses, and herpesviruses using ELISAs and Microblot-Array panels. Additionally, we performed PCR to detect viral RNA/DNA and evaluated anti-nuclear autoantibodies linked to systemic autoimmune conditions. LC patients showed significantly reduced levels of SARS-CoV-2 anti-spike IgG and IgA but increased levels of endemic coronaviruses OC43 and HKU1 anti-spike IgG, suggesting immunological imprinting potentially driven by these coronaviruses. Furthermore, LC patients had higher levels of SARS-CoV-2 anti-spike IgM compared to anti-Spike IgG, possibly indicating impaired class switching. Interestingly, cytomegalovirus (CMV) p65 IgG levels were lower in LC patients and negatively correlated with fatigue severity. This study highlights immunological imprinting by seasonal coronaviruses and impaired antibody class switching as potential causes of SARS-CoV-2 immune escape and persistence in LC patients. Furthermore, our findings suggest an inverse association between CMV p65 IgG and fatigue severity in LC.},
}

Humans
Male
Female
*COVID-19/immunology/virology/complications
Antibodies, Viral/blood/immunology
Middle Aged
Immunoglobulin G/blood/immunology
Immunoglobulin M/blood
*SARS-CoV-2/immunology
Adult
Aged
*Herpesviridae Infections/immunology/virology/complications
Immunoglobulin A/blood
Seasons
Spike Glycoprotein, Coronavirus/immunology
Herpesviridae/immunology

@article {pmid40883696,
year = {2025},
author = {Kamal, SM and Al Qahtani, MS and Al Aseeri, A and Naghib, MEDM and Al Mazroua, AMM and Alshamrani, AMM and Al Mazroua, MM and AlHarbi, FSF},
title = {Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1082},
pmid = {40883696},
issn = {1471-2334},
}

@article {pmid40883647,
year = {2025},
author = {Fayyad-Kazan, M},
title = {MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {40883647},
issn = {1568-5608},
abstract = {Since the onset of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), elucidating the molecular regulators of viral pathogenesis and host response has been a critical international research objective. Among these, microRNAs (miRNAs), small non-coding RNAs, that modulate gene expression post-transcriptionally-have emerged as central orchestrators of host-virus interactions. This review exhaustively examines the roles of host-derived miRNAs in SARS-CoV-2 infection, including their roles in viral entry, replication, immune evasion, inflammation, and tissue injury. Dysregulation of certain miRNAs, such as miR-155, miR-146a, and miR-21, has been implicated in disease severity, comorbidities (such as diabetes, obesity), neurological complications, and pregnancy complications. In long COVID (PASC), chronic miRNA changes are linked to persistent inflammation, fibrosis, and cardiometabolic impairment. We emphasize current breakthroughs in miRNA research, including machine learning algorithms for miRNA-based disease stratification, CRISPR-engineered miRNA modulation, exosomal miRNA delivery platforms, and miRNA-adjuvanted vaccines. These advances highlight the potential of miRNAs as diagnostic biomarkers and therapeutic targets. Nevertheless, shortcomings persist in clinical validation, delivery optimization, and tissue-specific miRNA function elucidation. These gaps must be addressed to involve miRNAs in controlling current and future viral infections. This review consolidated differentially expressed miRNAs across disease stages, comorbidities, and clinical settings, providing a valuable resource for translational research and therapeutic innovation.},
}

@article {pmid40883052,
year = {2025},
author = {Mizuno, A},
title = {Stirring the POTS: Finding Symptom Patterns in Long COVID.},
journal = {JACC. Advances},
volume = {4},
number = {8},
pages = {101869},
doi = {10.1016/j.jacadv.2025.101869},
pmid = {40883052},
issn = {2772-963X},
}

@article {pmid40883051,
year = {2025},
author = {Al Mouslmani, M and Sawano, M and Arun, AS and Wu, Y and Shah, RM and Kaleem, S and Zhou, T and Murugiah, K and Lu, Y and Herrin, J and Bishop, P and Taub, P and Peixoto, AJ and Bhattacharjee, B and Iwasaki, A and Krumholz, HM},
title = {Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study.},
journal = {JACC. Advances},
volume = {4},
number = {8},
pages = {101873},
doi = {10.1016/j.jacadv.2025.101873},
pmid = {40883051},
issn = {2772-963X},
abstract = {BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID.

OBJECTIVES: The purpose of this study was to describe the experience of people reporting long COVID-associated POTS.

METHODS: We collected data from individuals aged ≥18 years with self-reported long COVID who participated in the Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) cohort, an online observational study. The study included participants surveyed from May 2022 to July 2023. POTS status was determined by self-reported diagnosis of POTS. We compared the demographics, symptoms, associated conditions, and health status of people with and without self-reported POTS.

RESULTS: Of the 578 individuals included, 167 (28.9%) reported new-onset POTS and 411 (71.1%) did not report POTS as one of their long COVID-associated conditions. Seventy-eight percent of participants with self-reported POTS were women (range, 18-74 years). Participants with self-reported POTS were younger, had more financial difficulties, more social isolation, more suicidal thoughts, worse health status measured by the EuroQoL visual analog scale, and reported higher rates of rapid heart rate after standing up, dizziness, palpitations, persistent chest pain, sudden chest pain, excessive fatigue, exercise intolerance, heat intolerance, brain fog, tinnitus, migraine, internal tremors, skin discoloration, and dry eyes, as well as new-onset myalgic encephalomyelitis/chronic fatigue syndrome and mast cell disorders.

CONCLUSIONS: Individuals with self-reported long COVID-associated POTS experienced substantial health burdens in various domains compared with those without self-reported POTS, highlighting the urgency for further research to understand the mechanism, characterize the physiological derangements, and target treatments so we can help these individuals.},
}

@article {pmid40880174,
year = {2025},
author = {Ferreira, AMS and Ferreira, FELL and Alverga, CCF and Nascimento, JAD and de Carvalho, ALB and de Freitas, GRM and de Moraes, JAC and Rocha, IDS and Silva, LTD and Alves, BCPDS and de Oliveira, CR and Cardoso, JRA and Anacleto, RMM and Pernambuco, L},
title = {Symptoms and Risk Factors for Long COVID: A Cross-Sectional Study in Primary Care.},
journal = {Journal of medical virology},
volume = {97},
number = {9},
pages = {e70579},
pmid = {40880174},
issn = {1096-9071},
support = {//This study was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) (ROR identifier: 00x0ma614)./ ; },
mesh = {Humans ; Female ; Male ; Middle Aged ; Cross-Sectional Studies ; *COVID-19/epidemiology/complications/diagnosis ; Primary Health Care ; Risk Factors ; Adult ; Aged ; Retrospective Studies ; Brazil/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; Young Adult ; Aged, 80 and over ; Sex Factors ; },
abstract = {This study aimed to determine the occurrence and risk factors for persistent symptoms after mild to moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients who presented in primary care during the 2021 pandemic. A retrospective cross-sectional survey was conducted in six public family health care units in Joao Pessoa, Brazil. A questionnaire with a set of 18 validated clinical outcomes was used to assess prolonged symptoms beyond 3 months of duration in 226 adults who had confirmed SARS-CoV-2 infection. Binary logistic regression models were used to estimate adjusted odds ratios (aOR) and risk factors for Long COVID. A total of 16 outcomes were significantly associated with Long COVID. The largest aOR were estimated for short-term memory loss, anxiety, and loss of attention. The risk factors for Long COVID included ≥ 5 symptoms (15.82, 7.33-34.15, p < 0.0001), female sex (aOR: 1.91, 95% CI: 1.03-3.53, p = 0.032), age 40-49 years (3.45, 1.14-10.51, p = 0.029), and age 70+ years (4.0, 1.01-15.51, p = 0.045). Findings highlight a high frequency of persistent symptoms in adults who initially had non-severe SARS-CoV-2 infection, who are predominantly of working age, and who did not present multiple comorbidities. This study supports the need for assessing clinical outcomes and risk factors on Long COVID in primary care using routinely recorded clinical outcomes.},
}

Humans
Female
Male
Middle Aged
Cross-Sectional Studies
*COVID-19/epidemiology/complications/diagnosis
Primary Health Care
Risk Factors
Adult
Aged
Retrospective Studies
Brazil/epidemiology
SARS-CoV-2
Surveys and Questionnaires
Young Adult
Aged, 80 and over
Sex Factors

@article {pmid40879554,
year = {2025},
author = {Herlitz, J and Pohl, A and Gerlach, AL},
title = {Googling as avoidance: anxiety responses to online health information about long COVID.},
journal = {Anxiety, stress, and coping},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/10615806.2025.2551018},
pmid = {40879554},
issn = {1477-2205},
abstract = {Background and Objectives: People search the internet for health information, although this increases anxiety and worry, particularly in the health-anxious. Applying the avoidance theory of worrying, we tested whether online health research serves to emotionally distance oneself from illness.Design and Method: Googling long COVID was compared to imagery of suffering from the disease in 60 participants. We assumed that anxiety responses to googling would be lower than during imagery, but higher than during baseline. Self-report, skin conductance (SCL), heart rate (HR), heart rate variability (HRV), and respiration rate (RR) indicated anxiety.Results: SCL was higher during imagery than googling. However, HR, high frequency HRV and RR signaled stronger activation by googling than imagery. Physiological measures demonstrated a stronger anxiety response to googling compared to baseline. Regarding self-report, an interaction effect of sequence and condition emerged. Those who started with googling reported higher levels of anxiety during imagery. Among participants who began with imagery, anxiety was elevated during googling compared to baseline, but there were no significant differences when compared to anxiety during imagery.Conclusions: Results at least partially support the notion that health-related internet research may serve to avoid the physical and self-reported anxiety responses.},
}

@article {pmid40876395,
year = {2025},
author = {Ayuso García, B and Pérez López, A and Besteiro Balado, Y and Romay Lema, E and Marchán-López, Á and Rabuñal Rey, R},
title = {Prevalence of symptoms and quality of life 3 years after COVID-19: Long term follow-up using the C19-YRS questionnaire in a Spanish hospital.},
journal = {Medicina clinica},
volume = {165},
number = {5},
pages = {107138},
doi = {10.1016/j.medcli.2025.107138},
pmid = {40876395},
issn = {1578-8989},
abstract = {INTRODUCTION: Post-COVID syndrome can hinder the quality of life of patients. This study aims at describing this syndrome and its natural history.

METHODS: Prospective study including 443 inpatient and outpatient survivors of COVID-19 acquired between March and May 2020. Patients with dementia, nursing home residents, and those rejecting participation were excluded. Symptoms were assessed 10 and 36 months after the infection using the C19-YRS questionnaire. The prevalence and severity of symptoms, as well as risk factors for symptom persistence were investigated.

RESULTS: At 10 months 62.3% of patients reported at least one symptom, down to 54.9% at 36 months. Fatigue (37.2%), dyspnea at exertion (33.4%), and anxiety (33.4%) were the most prevalent symptoms, all of which showed improvement at follow up. Domain-specific impairment was the strongest risk factor for symptom persistence. Most patients reported a similar health status (69.4%) and quality of life (71.4%) compared with their pre-infection condition.

CONCLUSIONS: Although frequent, post-COVID-19 symptoms improve over time, while quality of life remains stable compared to patients baseline status.},
}

@article {pmid40876137,
year = {2025},
author = {Hotez, PJ},
title = {COVID-19 vaccinations in America: Don't forget long COVID and the post-acute sequelae.},
journal = {Vaccine},
volume = {63},
number = {},
pages = {127676},
doi = {10.1016/j.vaccine.2025.127676},
pmid = {40876137},
issn = {1873-2518},
}

@article {pmid40875678,
year = {2025},
author = {Schapowal, A},
title = {[Long COVID, Post-COVID-Syndrom: Langzeitfolgen von SARS-CoV-2-Infektionen und Nutzen von Ginkgo biloba].},
journal = {Complementary medicine research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1159/000548075},
pmid = {40875678},
issn = {2504-2106},
abstract = {Background Long COVID and Post-COVID Syndrome are long-term consequences of SARS-CoV-2 infections, causing a range of physical, cognitive, and psychological symptoms such as fatigue, shortness of breath, memory impairment, and sleep disturbances. The exact pathophysiology remains unclear but is thought to involve persistent viral particles, microvascular dysfunction, autoimmune reactions, and autonomic nervous system dysregulation. Summary Diagnosing Long COVID is challenging due to the lack of standardized tests. A multimodal treatment approach is recommended, incorporating symptomatic medication, physiotherapy, psychotherapy, as well as nutritional and exercise therapy. One promising complementary therapeutic option is the use of standardized Ginkgo biloba extracts. Their antioxidant, anti-inflammatory, and neuroprotective properties may help alleviate cognitive impairments, fatigue, and cardiovascular symptoms. Initial studies and case reports suggest positive effects, but further clinical trials are necessary to confirm efficacy. Key Messages Long COVID and Post-COVID Syndrome affect multiple organ systems and significantly reduce quality of life. Diagnosis remains difficult due to the absence of specific tests. A multimodal therapy approach is currently the most promising strategy. Standardized Ginkgo biloba extracts show potential benefits for neurocognitive and cardiovascular symptoms in early studies.},
}

@article {pmid40875136,
year = {2025},
author = {Sala, MA and Koralnik, IJ},
title = {Five years later: no short answers for Long COVID.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {40875136},
issn = {2509-2723},
}

@article {pmid40874015,
year = {2025},
author = {Wang, Z and Nirantharakumar, K and Copland, A and Quelch, D and Thayakaran, R and Chandan, JS and Ferguson, J and Brookes, M and Lewis, M and Rajoriya, N and Trudgill, N and Arasaradnam, R and Bradberry, S and Haroon, S and Bhala, N and Adderley, NJ},
title = {Estimating inequality in alcohol-related liver disease burden in the UK, 2009 to 2020: a population-based study using routinely collected data.},
journal = {The Lancet. Primary care},
volume = {1},
number = {1},
pages = {None},
pmid = {40874015},
issn = {3050-5143},
abstract = {BACKGROUND: There is a need to understand the preventable burden of alcohol-related liver disease (ARLD) and to improve the identification of individuals at high risk. We aimed to establish reliable and stratified epidemiological data to understand the burden of ARLD and the inequalities in this burden related to ethnicity, socioeconomic factors, and region in the UK.

METHODS: Data were extracted from Clinical Practice Research Datalink Aurum, a primary care database that includes 20% of UK general practices. The study period was Jan 1, 2009, to Dec 31, 2020; all patients aged 18 years and older registered at a participating practice were eligible for inclusion. Hospital admission data were extracted from linked Hospital Episode Statistics (HES) and ARLD-specific mortality data were obtained from Office for National Statistics Death Registration Data. Several analytical approaches were used, as follows: yearly cross-sectional and cohort analyses to calculate the annual prevalence and incidence of ARLD, respectively; a retrospective, matched, open cohort study to assess all-cause mortality rates (in which patients without liver disease were matched with patients with ARLD on the basis of age, sex, ethnicity, and geographical region); and a retrospective, open cohort analysis to evaluate all-cause hospitalisation rates. Hospitalisation rates were calculated in those with ARLD only. We explored different definitions of ARLD, and our primary definition was definite ARLD (ie, a coded clinical record specifying ARLD). Incidence and prevalence were stratified by age, sex, ethnicity, deprivation (Index of Multiple Deprivation [IMD] quintile) and geographical region.

FINDINGS: During the study period, 19 534 887 patients from 1491 practices were eligible for inclusion in our study. For definite ARLD exposure, 257 544 patients were included in the all-cause mortality outcome analysis, of whom 51 510 were diagnosed with definite ARLD; while among the 50 409 patients with definite ARLD for whom HES-linked data were available, 37 142 had one or more hospital admissions. Prevalence of definite ARLD rose from 154 to 243 per 100 000 population from 2009 to 2020. Incidence increased from 18·6 to 30·3 per 100 000 person-years between 2009 and 2019, and then decreased to 24·7 per 100 000 person-years in 2020. Prevalence and incidence of ARLD by age, sex, ethnicity, geographical region, and IMD quintile increased between 2009 and 2020. The overall adjusted all-cause mortality hazard ratio (HR) for those with definite ARLD compared with no liver disease was 4·30 (95% CI 4·20-4·41). The effect of ARLD on mortality was more pronounced in younger than older age groups (eg, adjusted HR of 21·86 [95% CI 18·23-26·20]) in those aged 30-39 years vs 2·19 [2·09-2·29] in those ≥70 years) and in females than in males (5·61 [5·35-5·88] vs 3·93 [3·83-4·04]). The overall incidence rate for hospitalisations in patients with definite ARLD was 1·17 per person-year. Hospitalisation rates were higher in females (adjusted incidence rate ratio 1·03 [95% CI 1·01-1·06]) and in patients in more deprived groups (1·16 [1·10-1·21] in the most deprived IMD quintile vs the least deprived quintile).

INTERPRETATION: Our findings indicate an increasing burden of ARLD in the UK. Raising awareness of disparities in health outcomes in affected groups could facilitate earlier and more targeted interventions.

FUNDING: National Institute for Health and Care Research Clinical Research Network West Midlands.},
}

@article {pmid40873616,
year = {2025},
author = {Goulart, CDL and Maldaner, V and Alves, CCA and Milani, M and Milani, J and Gonçalves da Costa, AC and Alves, ML and Borges, RF and Sobral, CCCH and Moraes, LA and Coutinho, JC and Gomes, NO and Tolfo Franzoni, L and Ferrari, F and Borghi-Silva, A and Cahalin, LP and Cipriano, GFB and Cipriano Junior, G and Stein, R},
title = {Recovery from COVID-19: a 12-month follow-up study on cardiorespiratory fitness and pulmonary function.},
journal = {Frontiers in cardiovascular medicine},
volume = {12},
number = {},
pages = {1638317},
pmid = {40873616},
issn = {2297-055X},
abstract = {INTRODUCTION AND AIM: Long COVID, characterized by persistent symptoms after acute infection, poses a major public health challenge. Understanding its long-term effects is crucial, particularly in relation to cardiorespiratory recovery. This study aimed to assess changes in cardiorespiratory fitness (CRF) and pulmonary function (PF) over 12 months following acute COVID-19, addressing a significant gap in current knowledge about the disease's lasting impact.

METHODS: This prospective cohort study included 29 individuals previously diagnosed with post-acute COVID-19. The baseline data were collected during the acute phase of infection. Participants underwent clinical evaluation, cardiopulmonary exercise testing (CPET), spirometry, and maximal inspiratory pressure (MIP) measurement at baseline and again after 12 months.

RESULTS: After one-year, significant improvements were observed across several CPET parameters, including VE/MVV ratio (Cohen's D = 0.66), peak oxygen uptake (VO2peak) in both absolute and relative terms (ml/min: d = 0.67; and ml/kg/min: d = 0.45), oxygen uptake efficiency slope (OUES; D = 0.47) and a reduction in VE/VCO2 slope (D = 0.80). Pulmonary function improved with increases in % predicted forced expiratory volume in 1 s (FEV1; d = 0.67) and forced vital capacity (FVC; D = 0.67). MIP improved significantly (D = 0.67), and the prevalence of inspiratory muscle weakness decreased from 20.7% at baseline to 3.5% at follow-up.

CONCLUSION: Despite the severity of their initial illness, patients demonstrated substantial recovery in CRF, PF, and inspiratory muscle strength over 12 months.},
}

@article {pmid40872911,
year = {2025},
author = {Zambrano-Sánchez, G and Rivadeneira, J and Manterola, C and Otzen, T and Fuenmayor-González, L},
title = {Immunization as Protection Against Long COVID in the Americas: A Scoping Review.},
journal = {Vaccines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/vaccines13080822},
pmid = {40872911},
issn = {2076-393X},
support = {Folio (85220114).//ANID + SUBVENCIÓN A INSTALACIÓN EN LA ACADEMIA CONVOCATORIA AÑO 2022/ ; },
abstract = {INTRODUCTION: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic's impact, there is a lack of evidence of its efficacy in preventing long COVID in the region.

METHODS: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables.

RESULTS: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies.

CONCLUSIONS: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes.},
}

@article {pmid40872813,
year = {2025},
author = {Muthiah, D and Vaddadi, K and Liu, L},
title = {Breathless Aftermath: Post-COVID-19 Pulmonary Fibrosis.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/v17081098},
pmid = {40872813},
issn = {1999-4915},
support = {R01HL157450, R21AI189861 and P30GM149368//National Institutes of Health grants, Oklahoma Center for Adult Stem Cell Research and the Lundberg-Kienlen Endowment fund (to LL)/ ; },
mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology ; SARS-CoV-2 ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {A significant number of individuals recovering from COVID-19 continue to experience persistent symptoms, collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or long COVID. Among these complications, post-COVID-19 pulmonary fibrosis (PC19-PF) is one of the most severe long-term outcomes, characterized by progressive lung scarring, chronic respiratory impairment, and reduced quality of life. Despite the increasing prevalence of PC19-PF, its underlying mechanisms remain poorly understood. In this review, we provide a comprehensive overview of PC19-PF, including its epidemiology, clinical manifestations, diagnostic strategies, and mechanistic insights. Additionally, we highlight the shared pathways between PC19-PF and other fibrotic lung diseases and discuss emerging therapeutic strategies. This review consolidates emerging insights from both clinical and experimental studies to advance our understanding of PC19-PF pathogenesis and guide the development of mechanism-based therapeutic approaches.},
}

Humans
*COVID-19/complications
*Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology
SARS-CoV-2
Lung/pathology/virology
Post-Acute COVID-19 Syndrome
Quality of Life

@article {pmid40872762,
year = {2025},
author = {Cao, Y and Wang, Y and Huang, D and Tan, YJ},
title = {The Role of SARS-CoV-2 Nucleocapsid Protein in Host Inflammation.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/v17081046},
pmid = {40872762},
issn = {1999-4915},
support = {T2EP30121-0012//Ministry of Education/ ; },
mesh = {Humans ; *Coronavirus Nucleocapsid Proteins/immunology/metabolism ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology ; *Inflammation/immunology/virology ; *Phosphoproteins/immunology/metabolism ; Host-Pathogen Interactions ; Animals ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery-known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders.},
}

Humans
*Coronavirus Nucleocapsid Proteins/immunology/metabolism
*COVID-19/immunology/virology
*SARS-CoV-2/immunology
*Inflammation/immunology/virology
*Phosphoproteins/immunology/metabolism
Host-Pathogen Interactions
Animals

@article {pmid40869608,
year = {2025},
author = {Popa, MV and Gurzu, IL and Handra, CM and Mandanach, C and Gurzu, B and Mîndru, DE and Duceac Covrig, M and Ciuhodaru, MI and Duceac, LD},
title = {Long COVID in Healthcare Workers from a Pediatric Hospital in Romania: A Cross-Sectional Study of Prevalence, Symptom Burden, and the Role of Vaccination and Reinfection.},
journal = {Journal of clinical medicine},
volume = {14},
number = {16},
pages = {},
doi = {10.3390/jcm14165782},
pmid = {40869608},
issn = {2077-0383},
abstract = {Background/Objectives: Long COVID, characterized by persistent symptoms following SARS-CoV-2 infection, poses a significant occupational health concern among healthcare workers (HCWs). This study aimed to evaluate the prevalence of long COVID, symptom patterns, work-related impact, and vaccination status among healthcare personnel in a Romanian pediatric hospital. Methods: A cross-sectional study was conducted in 2024 among 903 hospital employees during routine occupational health assessments. Data were collected using structured questionnaires and medical records, focusing on previous SARS-CoV-2 infection, vaccination status, persistent symptoms, and functional impact. Results: Long COVID was identified in 28.6% of participants, with excessive fatigue (53.5%), musculoskeletal pain, respiratory difficulties, and cognitive complaints being the most common symptoms. Staff with chronic comorbidities or increased exposure risk had significantly higher rates of functional impairment. Fewer reinfections were reported among vaccinated individuals; however, vaccination was not significantly associated with the presence of long COVID symptoms. Older age and comorbidities were correlated with higher risk. Conclusions: The findings underline the need for long-term occupational health strategies and individualized support programs for HCWs affected by long COVID, particularly in high-risk groups.},
}

@article {pmid40869200,
year = {2025},
author = {Lesgards, JF and Cerdan, D and Perronne, C},
title = {Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167879},
pmid = {40869200},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/prevention & control/physiopathology ; *COVID-19 Vaccines/adverse effects/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin-angiotensin-aldosterone system (RAAS), the kininogen-kinin-kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects.},
}

Humans
*COVID-19/immunology/prevention & control/physiopathology
*COVID-19 Vaccines/adverse effects/immunology
SARS-CoV-2/immunology
Spike Glycoprotein, Coronavirus/immunology/metabolism
Post-Acute COVID-19 Syndrome

@article {pmid40868989,
year = {2025},
author = {Cimmino, G and D'Elia, S and Morello, M and Titolo, G and Luisi, E and Solimene, A and Serpico, C and Conte, S and Natale, F and Loffredo, FS and Bianco, A and Golino, P},
title = {Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167668},
pmid = {40868989},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/pathology ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology/pathology ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu-characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)-and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals.},
}

Humans
*COVID-19/complications/pathology
SARS-CoV-2
*Cardiovascular Diseases/etiology/pathology
Lung/pathology/virology
Post-Acute COVID-19 Syndrome

@article {pmid40868961,
year = {2025},
author = {Florea, CE and Bălaș-Maftei, B and Rotaru, A and Abudanii, PL and Vieru, ST and Grigoriu, M and Stoian, A and Manciuc, C},
title = {Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/life15081314},
pmid = {40868961},
issn = {2075-1729},
abstract = {Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body's immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver's central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection.},
}

@article {pmid40868937,
year = {2025},
author = {Troisi, M and Troisi, S and Vitiello, L and Strianese, D and Bellucci, C and Rinaldi, M and D'Andrea, L and Costagliola, C},
title = {Ocular and Neurological Sequelae in Long COVID: Dry Eye, Asthenopia, Sleep Disorders, Asthenia, and Restless Legs Syndrome-A Case Report with Literature Review.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/life15081289},
pmid = {40868937},
issn = {2075-1729},
abstract = {This case report presents a unique constellation of symptoms-including dry eye disease, visual and general asthenia, sleep disturbances, and restless legs syndrome-in a patient with a recent history of coronavirus disease 2019 (COVID-19) infection. While these symptoms have individually been associated with either COVID-19 or long COVID, their concurrent presentation and the simultaneous, positive response across all manifestations to a combined therapeutic regimen have not been previously described in a single case. The patient demonstrated notable improvement in both ocular and systemic symptoms following a six-week treatment with topical tear substitutes and oral administration of melatonin, and a multivitamin supplement including B-complex vitamins, antioxidants, and neuroprotective agents (Colinplus Delta[®], Farmaplus Italia Srl, Via Giovanni Porzio 4, 80143 Napoli, Italy). This response suggests a possible shared pathophysiological mechanism underlying these manifestations, potentially involving post-viral neuroinflammation, immune dysregulation, oxidative stress, or autonomic dysfunction. This case report highlights the need for an increased awareness of the interconnected nature of ocular and neurological symptoms in long COVID and supports further research into non-invasive, multimodal treatment strategies for this emerging clinical spectrum.},
}

@article {pmid40868144,
year = {2025},
author = {Haagsma, AB and Otto, FG and de Sá Vianna, MLG and Maingue, PM and Muller, AP and de Oliveira, NHDS and Abbott, LA and da Silva, FPG and Klein, CK and Herzog, DM and Fantin Unruh, JCB and Schoeler, L and Miyasaki, D and Soni, JF and Stival, RSM and Baena, CP},
title = {Clinical Evaluation of COVID-19 Survivors at a Public Multidisciplinary Health Clinic.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081888},
pmid = {40868144},
issn = {2227-9059},
support = {3465//National Council for Scientific and Technological Development/ ; },
abstract = {Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53-196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03-1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset.},
}

@article {pmid40868113,
year = {2025},
author = {Brogna, C and Castellucci, G and Redwan, EM and Rubio-Casillas, A and Montano, L and Ciammetti, G and Giuliano, M and Viduto, V and Fabrowski, M and Lettieri, G and Marinaro, C and Piscopo, M},
title = {New Neonatal and Prenatal Approach to Home Therapy with Amoxicillin, Rifaximin, and Anti-Inflammatory Drugs for Pregnant Women with COVID-19 Infections-Monitoring of Fetal Growth as a Prognostic Factor: A Triple Case Series (N.A.T.H.A.N.).},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081858},
pmid = {40868113},
issn = {2227-9059},
abstract = {Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women-especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother-one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant-as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status.},
}

@article {pmid40868058,
year = {2025},
author = {Gonzaga, A and Martinez-Navarrete, G and Macia, L and Anton-Bonete, M and Cahuana, G and Tejedo, JR and Zorrilla-Muñoz, V and Fernandez-Jover, E and Andreu, E and Eguizabal, C and Pérez-Martínez, A and Solano, C and Hernández-Blasco, LM and Soria, B},
title = {Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081801},
pmid = {40868058},
issn = {2227-9059},
support = {ICI21/00016//Instituto de Salud Carlos III/ ; AVI-GVA-COVID19-068//Valencian Agency of Innovation(AVI)/ ; GVA-COVID19/2021-047//Valencian Agency of Innovation(AVI)/ ; NA//Al-Andalus Biopharma SL/ ; },
abstract = {Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC).},
}

@article {pmid40867811,
year = {2025},
author = {Villegas Sánchez, V and Chávez Pacheco, JL and Palacios Arreola, MI and Sierra-Vargas, MP and Colín Godinez, LA and Ahumada Topete, VH and Fernández Plata, R and Higuera-Iglesias, A and Lara-Lemus, R and Aquino-Gálvez, A and Torres-Espíndola, LM and Castillejos-López, M},
title = {A Systematic Review of Genetic Variants in Glutathione S-Transferase Genes and Their Dual Role in SARS-CoV-2 Pathogenesis: From Acute Respiratory Complications to Long COVID.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/antiox14080912},
pmid = {40867811},
issn = {2076-3921},
abstract = {Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID.},
}

@article {pmid40867133,
year = {2025},
author = {Tsaava, M and Basishvili, T and Sakhelashvili, I and Eliozishvili, M and Oniani, N and Lortkipanidze, N and Tarielashvili, M and Khoshtaria, L and Darchia, N},
title = {From Lockdowns to Long COVID-Unraveling the Link Between Sleep, Chronotype, and Long COVID Symptoms.},
journal = {Brain sciences},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/brainsci15080800},
pmid = {40867133},
issn = {2076-3425},
abstract = {Background/Objectives: Given the heterogeneous nature of long COVID, its treatment and management remain challenging. This study aimed to investigate whether poor pre-pandemic sleep quality, its deterioration during the peak of the pandemic, and circadian preference increase the risk of long COVID symptoms. Methods: An online survey was conducted between 9 October and 12 December 2022, with 384 participants who had recovered from COVID-19 at least three months prior to data collection. Participants were categorized based on the presence of at least one long COVID symptom. Logistic regression models assessed associations between sleep-related variables and long COVID symptoms. Results: Participants with long COVID symptoms reported significantly poorer sleep quality, higher perceived stress, greater somatic and cognitive pre-sleep arousal, and elevated levels of post-traumatic stress symptoms, anxiety, depression, and aggression. Fatigue (39.8%) and memory problems (37.0%) were the most common long COVID symptoms. Sleep deterioration during the pandemic peak was reported by 34.6% of respondents. Pre-pandemic poor sleep quality, its deterioration during the pandemic, and poor sleep at the time of the survey were all significantly associated with long COVID. An extreme morning chronotype consistently predicted long COVID symptoms across all models, while an extreme evening chronotype was predictive only when accounting for sleep quality changes during the pandemic. COVID-19 frequency, severity, financial impact, and somatic pre-sleep arousal were significant predictors in all models. Conclusions: Poor sleep quality before the pandemic and its worsening during the pandemic peak are associated with a higher likelihood of long COVID symptoms. These findings underscore the need to monitor sleep health during pandemics and similar global events to help identify at-risk individuals and mitigate long-term health consequences, with important clinical and societal implications.},
}

@article {pmid40866305,
year = {2025},
author = {Bombardieri, AM and Denoue, CF},
title = {Cervical sympathetic block to treat Long COVID: a scoping review.},
journal = {Regional anesthesia and pain medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/rapm-2025-106879},
pmid = {40866305},
issn = {1532-8651},
abstract = {BACKGROUND: Long COVID is a complex and poorly understood condition characterized by persistent symptoms such as autonomic dysfunction, fatigue, neurocognitive impairment, and olfactory disturbances. Current treatments offer limited and inconsistent benefits. Dysregulation of the sympathetic nervous system is increasingly recognized as a contributor to Long COVID pathophysiology. Cervical sympathetic block (CSB), a procedure that modulates sympathetic tone, has emerged as a potential therapeutic approach.

OBJECTIVE: To review the existing literature on CSB, for Long COVID, focusing on symptom outcomes, proposed mechanisms, and procedural considerations.

EVIDENCE REVIEW: A structured literature search across PubMed, Embase, Scopus, and Web of Science identified studies published between 2022 and March 2025 reporting on CSB in adults with Long COVID. Eligible articles included case reports, case series, observational studies, and one randomized controlled trial evaluating symptom outcomes after the procedure.

FINDINGS: Sixteen studies involving 224 patients were included. Most reported improvement in fatigue, brain fog, and autonomic symptoms, including reduced heart rate and enhanced orthostatic tolerance. Cognitive and psychiatric symptoms such as memory impairment, anxiety, and depression showed variable improvement. Olfactory recovery was inconsistent and appeared to depend on symptom severity. Symptom relief was observed after both unilateral and bilateral blocks, with some responses lasting up to 1 year. No serious complications were reported.

CONCLUSIONS: CSB may offer symptom relief in Long COVID, particularly for fatigue, brain fog, and dysautonomia. However, the evidence remains preliminary and limited by small sample sizes and methodological heterogeneity. Controlled trials are needed to establish efficacy and patient selection criteria.},
}

@article {pmid40865177,
year = {2025},
author = {De Miguel-Escribano, M and Martín-Garrido, I and Garrido-Montes, M and Pertusa-Mataix, R and Corchero-Gijón, J and Morillo, JSG},
title = {Brain hypometabolism and cognitive impairment in long COVID: Insights from [18F]FDG-PET-CT imaging and neurocognitive assessment.},
journal = {Medicina clinica},
volume = {165},
number = {5},
pages = {107140},
doi = {10.1016/j.medcli.2025.107140},
pmid = {40865177},
issn = {1578-8989},
abstract = {INTRODUCTION: Despite the progressive socioeconomic and healthcare recovery following the SARS-CoV-2 pandemic, its sequelae remain markedly evident today. Among them, Long COVID significantly impairs patient functionality and quality of life. Neurocognitive impairment stands out as one of its most debilitating manifestations.

PATIENTS AND METHODS: We assessed 16 patients diagnosed with Long COVID and neurocognitive dysfunction, quantifying the degree of impairment using cognitive evaluation tests and comparing these results with findings from prior [18F]FDG-PET-CT brain scans.

RESULTS: The mean cognitive test scores demonstrated significant impairment. Patients predominantly exhibited mild hypometabolism across various regions, with the cerebellum identified as the most frequently affected area. Those with more pronounced [18F]FDG-PET-CT abnormalities exhibited greater cognitive deficits. Greater hypometabolism and thalamic involvement were associated with lower cognitive assessment score.

CONCLUSION: We support the role of cerebral hypometabolism in the development of neurocognitive impairment associated with Long COVID, although its underlying pathophysiological mechanisms remain to be elucidated. We further endorse the potential link between cerebellar hypometabolism and cognitive decline. Greater severity in brain [18F]FDG-PET-CT abnormalities and thalamic dysfunction may correlate worse cognitive impairment.},
}

@article {pmid40864005,
year = {2025},
author = {Bryarly, M and Robbins, NM and Roberts, M and Cabrera, J and Parsonnet, J and Martin, C and Hernandez, RS and Barshikar, S and Vernino, S},
title = {Minimal Objective Autonomic Dysfunction in Long COVID.},
journal = {Journal of the American College of Cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacc.2025.04.038},
pmid = {40864005},
issn = {1558-3597},
}

@article {pmid40863252,
year = {2025},
author = {Srikanth, S and Boulos, JR and Ivankovic, D and Gonzales, L and Dean, D and Boccuto, L},
title = {Long COVID-19: A Concept Analysis.},
journal = {Infectious disease reports},
volume = {17},
number = {4},
pages = {},
pmid = {40863252},
issn = {2036-7430},
abstract = {Background/Objectives: In late 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic called the 'coronavirus disease 2019' (COVID-19). After the acute SARS-CoV-2 infection, many individuals (up to 33%) complained of unexplained symptoms involving multiple organ systems and were diagnosed as having Long COVID-19 (LC-19). Currently, LC-19 is inadequately defined, requiring the formation of consistent diagnostic parameters to provide a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy. LC-19 represents a significant burden on multiple levels. The reduced ability of workers to return to work or compromised work efficiency has led to consequences at national, economic, and societal levels by increasing dependence on community services. On a personal scale, the isolation and helplessness caused by the disease and its subsequent impact on the patient's mental health and quality of life are incalculable. Methods: In this paper, we used Walker and Avants' eight-step approach to perform a concept analysis of the term "Long COVID-19" and define its impact across these parameters. Results: Using this methodology, we provide an improved definition of LC-19 by connecting the clinical symptomology with previously under-addressed factors, such as mental, psychological, economic, and social effects. This definition of LC-19 features can help improve diagnostic procedures and help plan relevant healthcare services. Conclusions: LC-19 represents a complex and pressing public health challenge with diverse symptomology, an unpredictable timeline, and complex pathophysiology. This concept analysis serves as a tool for improving LC-19 definition, but it remains a dynamic disease with evolving diagnostic and therapeutic approaches, requiring deeper investigation and understanding of its long-term effects.},
}

@article {pmid40863220,
year = {2025},
author = {Ramamoorthy, R and Speciale, AR and West, EM and Hussain, H and Elumalai, N and Schmitz Abe, KE and Ramesh, MC and Agrawal, PB and Jayakumar, AR and Paidas, MJ},
title = {Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {8},
pages = {},
pmid = {40863220},
issn = {2079-9721},
support = {Department of Obstetrics, Gynecology, and Reproductive Sciences//University of Miami Miller School of Medicine/ ; Team Science Award//University of Miami Miller School of Medicine/ ; Charles M. Vallee Foundation//University of Miami Miller School of Medicine/ ; Muriel, Murrary & Robert Smith Foundation COVID-19 Research Fund//University of Miami Miller School of Medicine/ ; },
abstract = {BACKGROUND: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK).

METHODS: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR.

RESULTS: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice.

CONCLUSIONS: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae.},
}

@article {pmid40861640,
year = {2025},
author = {Chiang, MC and Satko, KM and Shin, C and Sperry, BP and Cabral, ML and Crockett, Z and Gao, R and Yong, RJ and Ang, SP and Burns, SL and Kim, AJ},
title = {Stellate Ganglion Block for the Management of Long COVID Symptoms: A Retrospective Cohort Study.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88680},
pmid = {40861640},
issn = {2168-8184},
abstract = {Introduction The efficacy of stellate ganglion block (SGB) for managing post-acute sequelae of SARS-CoV-2 (PASC) remains an area of active exploration. In this study, we performed a retrospective analysis of PASC symptom improvements following SGB. Methods We performed a retrospective, survey-based cohort study at a single institution of patients with a history of PASC who underwent SGB at one of three different sites within Boston, MA, USA, between September 2022 and September 2024. The intervention was outpatient, office-based, with one or more unilateral SGBs. Results Fifty-two patients were included in the analysis. On average, patients underwent three SGB injections. Most patients reported improvement in PASC symptoms after SGB treatment. The most commonly reported symptoms that showed improvement were brain fog, fatigue, dizziness, and headache. A quarter of patients reported experiencing at least one adverse effect that was mostly short-lived. Conclusion SGB reduced the severity of many PASC symptoms, although there was high variability in the duration of symptom improvement. Further high-quality randomized clinical trials are warranted to investigate SGBs for the effective treatment of PASC.},
}

@article {pmid40861631,
year = {2025},
author = {Lee, KD},
title = {Multidisciplinary Management for Anterior Cutaneous Nerve Entrapment Syndrome (ACNES): A Case Series Including a Long COVID-19 Patient.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88703},
pmid = {40861631},
issn = {2168-8184},
abstract = {Anterior cutaneous nerve entrapment syndrome (ACNES) is an underrecognized cause of chronic abdominal wall pain. While nerve block injections are typically used as conservative treatment, persistent or recurrent cases may require surgical neurectomy. This case series presents five patients, including a long COVID-19 case, who underwent surgical treatment for ACNES at our institution. We integrated clinical presentation, CT imaging, surgical findings, rehabilitation strategies, and histopathological analysis to explore a multidisciplinary treatment approach. Preoperative CT was helpful in detecting muscle atrophy or nerve visualization, which guided rehabilitation and surgical planning. Histopathology revealed chronic compressive neuropathy in all cases, even among those with mild symptoms, suggesting that pain severity alone should not dictate surgical indications. Rehabilitation was effective in reducing muscle contraction and localizing symptoms, contributing to postoperative success and recurrence prevention. Our findings support the importance of individualized, proactive management that combines imaging, surgery, and rehabilitation, and highlight the potential for COVID-19-related neuropathy to contribute to ACNES.},
}

@article {pmid40859683,
year = {2025},
author = {Gao, Y and Duan, C and Miao, T and Shen, Q and Yu, J and Shen, S and Chen, Y and Shen, Y and Zhang, K},
title = {Association between depression and three key COVID-19-related outcomes: The SHARE study.},
journal = {Human vaccines & immunotherapeutics},
volume = {21},
number = {1},
pages = {2551930},
doi = {10.1080/21645515.2025.2551930},
pmid = {40859683},
issn = {2164-554X},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Middle Aged ; Male ; Female ; Aged ; *Depression/epidemiology/complications ; Europe/epidemiology ; *COVID-19 Vaccines/administration & dosage ; SARS-CoV-2 ; Vaccination/statistics & numerical data ; Risk Factors ; },
abstract = {This study investigated the potential associations between preexisting depression and COVID-19 vaccination, SARS-CoV-2 infection risk, and long COVID among middle-aged and older Europeans, based on the Survey of Health, Ageing and Retirement in Europe (SHARE). A total of 31,115 participants were included to assess the relationship between depression and COVID-19 vaccination 11,146 to evaluate depression-related SARS-CoV-2 infection risk, and 11,142 to study the impact of depression on the occurrence of long COVID. Multivariable logistic model was performed and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Compared to non-depressed individuals, those with depression were 0.72 times less likely to receive the COVID-19 vaccine (95% CI: 0.67-0.77), had a 1.15 times higher risk of SARS-CoV-2 infection (95% CI: 1.02-1.30), and were 1.21 times more likely to develop long COVID (95% CI: 1.05-1.38), with these associations strengthening as the severity of depression increased. Preexisting depression might be linked to reduced COVID-19 vaccination odds and an elevated risk of SARS-CoV-2 infection and long COVID, although further high-quality prospective studies with larger samples are needed to confirm the findings.},
}

Humans
*COVID-19/epidemiology/prevention & control
Middle Aged
Male
Female
Aged
*Depression/epidemiology/complications
Europe/epidemiology
*COVID-19 Vaccines/administration & dosage
SARS-CoV-2
Vaccination/statistics & numerical data
Risk Factors

@article {pmid40859262,
year = {2025},
author = {Ballhausen-Lübcker, S and Ruß, AK and Lieb, W and Schäfer, A and Krist, L and Fricke, J and Scheibenbogen, C and Rabe, KF and Maetzler, W and Maetzler, C and Laudien, M and Frank, D and Heyckendorf, J and Miljukov, O and Haeusler, KG and El Mokhtari, NE and Witzenrath, M and Vehreschild, JJ and Appel, KS and Chaplinskaya-Sobol, I and Tamminga, T and Nürnberger, C and Schmidbauer, L and Morbach, C and Störk, S and Reese, JP and Keil, T and Heuschmann, P and Schreiber, S and Krawczak, M and Bahmer, T},
title = {Subdomains of Post-COVID Syndrome (PCS) - a population-based study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1072},
pmid = {40859262},
issn = {1471-2334},
abstract = {PURPOSE: 'Post-COVID Syndrome' (PCS), which encompasses the multifaceted sequelae of COVID-19, can be severity-graded by a previously defined score encompassing 12 different long-term symptom complexes. The PCS score was shown to have two main predictors, namely acute COVID-19 severity and individual resilience. The purpose of the present study was to verify these predictors and to assess their detailed relationship to the symptom complexes constituting the PCS score.

METHODS: The study drew upon a largely expanded dataset (n = 3,372) from COVIDOM, the cohort study underlying the original PCS score definition. Classification and Regression Tree (CART) analysis served to resolve the detailed relationship between the predictors and the constituting symptom complexes of the PCS score.

RESULTS: Among newly recruited COVIDOM participants (n = 1,930), the PCS score was again found to be associated with both its putative predictors. Of the score-constituting symptom complexes, neurological symptoms, sleep disturbance, and fatigue were predicted by individual resilience whereas the acute disease severity predicted exercise intolerance, chemosensory deficits, joint or muscle pain, signs of infection, and fatigue. These associations inspired the definition of two novel PCS scores that included the above-mentioned subsets of symptom complexes only. Similar to the original PCS score, both novel scores were found to be inversely correlated with quality of life as measured by the EQ-5D-5L index.

CONCLUSION: The two newly defined PCS scores may enable a more refined assessment of PCS severity, both in a research context and to delineate distinct PCS subdomains with possibly different therapeutic and interventional needs in clinical practise.},
}

@article {pmid40858480,
year = {2025},
author = {Crosskey, M and McIntee, T and Preiss, S and Brannock, D and Baratta, JM and Yoo, YJ and Hadley, E and Blanceró, F and Chew, R and Loomba, J and Bhatia, A and Chute, CG and Haendel, M and Moffitt, R and Pfaff, ER and , },
title = {Re-engineering a machine learning phenotype to adapt to the changing COVID-19 landscape: a machine learning modelling study from the N3C and RECOVER consortia.},
journal = {The Lancet. Digital health},
volume = {},
number = {},
pages = {100887},
doi = {10.1016/j.landig.2025.100887},
pmid = {40858480},
issn = {2589-7500},
abstract = {BACKGROUND: In 2021, we used the National COVID Cohort Collaborative (N3C) as part of the National Institutes of Health RECOVER Initiative to develop a machine learning pipeline to identify patients with a high probability of having post-acute sequelae of SARS-CoV-2 infection or long COVID. However, the increased home testing, missing documentation, and reinfections that characterise the pandemic beyond 2022 necessitated the re-engineering of our original model to account for these changes in the COVID-19 research landscape.

METHODS: Trained on 72 745 patient records (36 238 with long COVID and 36 507 with no evidence of long COVID), our updated XGBoost model gathered data for each patient in overlapping 100-day periods that progressed through time and issued a probability of long COVID for each 100-day period. We ran the model on patients in N3C (n=5 875 065) who met at least one of the following criteria from Jan 1, 2020, to June 22, 2023: a U07·1 (COVID-19) diagnosis code; a positive SARS-CoV-2 test; a U09·9 (post-acute sequelae of SARS-CoV-2 infection) diagnosis code; a prescription for nirmatrelvir-ritonavir or remdesivir; or an M35·81 (multisystem inflammatory syndrome in children [MIS-C]) diagnosis code. Each patient was given a model score that predicted long COVID status for each 100-day window in which they were aged ≥18 years. If a patient had known acute COVID-19 during any 100-day window (including reinfections), we censored the data from 7 days before the diagnosis or positive test date to 28 days after. We ran the model on controls selected from pre-2020 data to assess the likelihood of false positives.

FINDINGS: The updated model had an area under the receiver operating characteristic curve of 0·90. Precision and recall could be adjusted according to a given use case, depending on whether greater sensitivity or specificity was warranted. Using our model, we estimate the overall prevalence of long COVID among the COVID-19 positive cohort within N3C repository to be 10.4%.

INTERPRETATION: By eschewing the COVID-19 index date as an anchor point for analysis, we can assess the probability of long COVID among patients who might have tested at home, or with suspected (but untested) cases of COVID-19, or multiple SARS-CoV-2 reinfections. We view this exercise as a model for maintaining and updating any machine learning pipeline used for clinical research and operations.

FUNDING: National Institutes of Health RECOVER Initiative.},
}

@article {pmid40857408,
year = {2025},
author = {Bayarri-Olmos, R and Bain, W and Iwasaki, A},
title = {The role of complement in long COVID pathogenesis.},
journal = {JCI insight},
volume = {10},
number = {16},
pages = {},
doi = {10.1172/jci.insight.194314},
pmid = {40857408},
issn = {2379-3708},
mesh = {Humans ; *COVID-19/immunology/complications ; *Complement System Proteins/immunology ; SARS-CoV-2/immunology ; Immunity, Innate/immunology ; Inflammation/immunology ; Complement Activation ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a debilitating condition that can develop after a SARS-CoV-2 infection and is characterized by a wide range of chronic symptoms, including weakness, neurocognitive impairment, malaise, fatigue, and many others, that affect multiple organ systems. At least 10% of individuals with a previous infection may develop long COVID, which affects their ability to perform daily functions and work. Despite its severity and widespread impact, this multisystemic condition remains poorly understood. Recent studies suggest that dysregulation of the complement system, a key component of the innate immune response, may contribute to the pathogenesis of long COVID, particularly in connection with coagulation, inflammation, and vascular injury. In this Review, we examine the evidence linking complement system dysregulation to long COVID and explore its potential role in driving disease pathology.},
}

Humans
*COVID-19/immunology/complications
*Complement System Proteins/immunology
SARS-CoV-2/immunology
Immunity, Innate/immunology
Inflammation/immunology
Complement Activation
Post-Acute COVID-19 Syndrome

@article {pmid40852766,
year = {2025},
author = {Ling, J and Li, J},
title = {What could cause the reactivation of Epstein-Barr virus in individuals with long COVID.},
journal = {Emerging microbes & infections},
volume = {},
number = {},
pages = {2552712},
doi = {10.1080/22221751.2025.2552712},
pmid = {40852766},
issn = {2222-1751},
}

@article {pmid40848989,
year = {2025},
author = {Liu, B and Song, S and Liu, W and Hu, Y and Wei, C and Zhou, L and Sun, Q and Tian, W and Chu, RYK and Wong, ICK and Hung, IFN and Wan, EYF and Li, X and Chui, CSL and Chan, EWY and Wong, CKH and Lai, FTT},
title = {Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: a population-based cohort study.},
journal = {The Journal of infection},
volume = {},
number = {},
pages = {106597},
doi = {10.1016/j.jinf.2025.106597},
pmid = {40848989},
issn = {1532-2742},
abstract = {BACKGROUND: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination.

METHODS: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list.

RESULTS: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96-313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1,000 person-years (95% CI: 68.18-69.37). In contrast, the COVID-19/unvaccinated group (9,455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85-88.35). The COVID-19/vaccinated group (8,232 cases) showed a moderated rate (72.84; 95% CI: 71.27-74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23-1.29) for unvaccinated and 1.08 (95% CI: 1.05-1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups.

INTERPRETATION: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.

FUNDING: Health and Meical Research Fund (Health Bureau, reference number: COVID19F01, 22211202) and Collaborative Research Fund (Research Grants Council, reference number: C7154-20GF).},
}

@article {pmid40848897,
year = {2025},
author = {Moreira Vidal, KS and Cavendish, BA and Goerigk, S and Batista, M and Oliveira Lima, AR and Pinto, BS and Neto Domingos, AA and de Sousa, JP and Pelosof, R and Bertola, L and Silva, V and Suemoto, CK and Razza, LB and Bikson, M and Pilloni, G and Charvet, L and Silva, PHR and Brunoni, AR},
title = {Transcranial direct current stimulation plus cognitive training for cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection: a randomized, double-blind, sham-controlled trial.},
journal = {Brain stimulation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.brs.2025.08.018},
pmid = {40848897},
issn = {1876-4754},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) is characterized by persistent cognitive deficits alongside anxiety and depression symptoms that adversely affect quality of life. Cognitive training (CT) programs and non-invasive neuromodulation, specifically transcranial direct current stimulation (tDCS), have each shown promise for alleviating similar deficits in non-clinical populations. However, their combined efficacy has not yet been evaluated in PASC patients. Therefore, this study aimed to determine whether the combination of CT and tDCS produces benefits for cognitive and mood-related symptoms in individuals with PASC.

METHODS: We conducted a double-blind, randomized, sham-controlled clinical trial in adults aged 18-75 with confirmed SARS-CoV-2 infection within the past six months and persisting cognitive complaints. They were randomized to a 4-week in-person intervention of 20 weekday sessions of either active (2 mA anodal-left, cathodal-right prefrontal stimulation) or sham tDCS paired with an app-based CT program. Primary outcomes were six standardized neuropsychological tests assessing verbal memory, working memory, executive functioning, attention, and language, administered at baseline and immediately post-intervention. As secondary outcomes, we assessed changes in depression and anxiety symptoms over the treatment period.

RESULTS: Sixty participants (mean age 43.8 ± 13.2 years, 71.7% women) were randomized to active tDCS + CT or sham tDCS + CT groups, and 52 finished the trial. Compared to sham, tDCS + CT resulted in significantly greater improvement in tests evaluating inhibitory control (effect size [ES] = 0.07, 95% CI 0 to 0.23, p = 0.046), processing speed (ES = 0.08, 95% CI 0 to 0.25, p = 0.034), and divided attention (ES = 0.08, 95% CI 0 to 0.24, p = 0.039), but not in tests evaluating other domains. Both groups improved similarly in depression and anxiety symptoms. Participant's and rater's active guess rates did not differ between groups (ps > 0.20).

CONCLUSION: An intervention with prefrontal targeted tDCS + CT in patients with PASC with cognitive complaints might be effective in improving attention, processing speed and inhibitory control, although further studies are warranted to prospectively confirm these findings.

CLINICALTRIALS: GOV: NCT05389592.},
}