@article {pmid40473290,
year = {2025},
author = {Jamieson, A and Saikhan, LA and Raman, B and Alghamdi, L and Cheetham, NJ and Conde, P and Dobson, R and Fernández-Sanlés, A and Folarin, A and Goudswaard, LJ and Hamill Howes, L and Jones, S and Neubauer, S and Orini, M and Pierce, I and Ranjan, Y and Rapala, A and Smith, SM and Sudre, C and Thompson, EJ and Wild, J and Williams, D and Wong, A and Steves, CJ and Timpson, N and Chaturvedi, N and Hughes, A},
title = {Cohort profile: characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19 - providing the evidence base for health care services (CONVALESCENCE) in the UK.},
journal = {BMJ open},
volume = {15},
number = {6},
pages = {e094760},
doi = {10.1136/bmjopen-2024-094760},
pmid = {40473290},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/epidemiology/complications/physiopathology/therapy ; Male ; Female ; United Kingdom/epidemiology ; Case-Control Studies ; Adult ; Middle Aged ; SARS-CoV-2 ; Longitudinal Studies ; *Convalescence ; Aged ; Post-Acute COVID-19 Syndrome ; Adolescent ; Child ; },
abstract = {PURPOSE: The pathogenesis of the long-lasting symptoms which can follow an infection with the SARS-CoV-2 virus ('long covid') is not fully understood. The 'COroNaVirus post-Acute Long-term EffectS: Constructing an evidENCE base' (CONVALESCENCE) study was established as part of the Longitudinal Health and Wellbeing COVID-19 UK National Core Study. We performed a deep phenotyping case-control study nested within two cohorts (the Avon Longitudinal Study of Parents and Children and TwinsUK) as part of CONVALESCENCE.

PARTICIPANTS: From September 2021 to May 2023, 349 participants attended the CONVALESCENCE deep phenotyping clinic at University College London. Four categories of participants were recruited: cases of long covid (long covid(+)/SARS-CoV-2(+)), alongside three control groups: those with neither long covid symptoms nor evidence of prior COVID-19 (long covid(-)/SARS-CoV-2(-); control group 1), those who self-reported COVID-19 and had evidence of SARS-CoV-2 infection, but did not report long covid (long covid(-)/SARS-CoV-2(+); control group 2) and those who self-reported persistent symptoms attributable to COVID-19 but no evidence of SARS-CoV-2 infection (long covid(+)/SARS-CoV-2(-); control group 3). Remote wearable measurements were performed up until February 2024.

FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the CONVALESCENCE cohort. Of the 349 participants, 141 (53±15 years old; 21 (15%) men) were cases, 89 (55±16 years old; 11 (12%) men) were in control group 1, 75 (49±15 years old; 25 (33%) men) were in control group 2 and 44 (55±16 years old; 9 (21%) men) were in control group 3.

FUTURE PLANS: The study aims to use a multiorgan score calculated as the cumulative total for each of nine domains (ie, lung, vascular, heart, kidney, brain, autonomic function, muscle strength, exercise capacity and physical performance). The availability of data preceding acute COVID-19 infection in cohorts may help identify the consequences of infection independent of pre-existing subclinical disease and also provide evidence of determinants that influence the development of long covid.},
}

Humans
*COVID-19/epidemiology/complications/physiopathology/therapy
Male
Female
United Kingdom/epidemiology
Case-Control Studies
Adult
Middle Aged
SARS-CoV-2
Longitudinal Studies
*Convalescence
Aged
Post-Acute COVID-19 Syndrome
Adolescent
Child

@article {pmid40472281,
year = {2025},
author = {Wolock, CJ and Jacob, S and Bennett, JC and Elias-Warren, A and O'Hanlon, J and Kenny, A and Jewell, NP and Rotnitzky, A and Cole, SR and Weil, AA and Chu, HY and Carone, M},
title = {Investigating Symptom Duration Using Current Status Data: A Case Study of Postacute COVID-19 Syndrome.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/EDE.0000000000001882},
pmid = {40472281},
issn = {1531-5487},
abstract = {BACKGROUND: For infectious diseases, characterizing symptom duration is of clinical and public health importance. Symptom duration may be assessed by surveying infected individuals and querying symptom status at the time of survey response. For example, in a severe acute respiratory syndrome coronavirus 2 testing program at the University of Washington, participants were surveyed at least 28 days after testing positive and asked to report current symptom status. This study design yielded current status data: outcome measurements for each respondent consisted only of the time of survey response and a binary indicator of whether symptoms had resolved by that time. Such study design benefits from limited risk of recall bias, but analyzing the resulting data necessitates tailored statistical tools.

METHODS: We review methods for current status data and describe a novel application of modern nonparametric techniques to this setting. The proposed approach is valid under weaker assumptions compared with existing methods, allows the use of flexible machine learning tools, and handles potential survey nonresponse. Our method relies on the assumption that the survey response time is conditionally independent of symptom resolution time within strata of measured covariates, and we propose an approach to assess the sensitivity of results to deviations from conditional independence.

RESULTS: From the university study, we estimate that 19% of participants experienced ongoing symptoms 30 days after testing positive, decreasing to 7% at 90 days. We found the estimates to be more sensitive to violations of the conditional independence assumption at 30 days compared with 90 days. Female sex, fatigue during acute infection, and higher viral load were associated with slower symptom resolution.

CONCLUSION: The proposed method and accompanying sensitivity analysis procedure provide tools for investigators faced with current status data.},
}

@article {pmid40470597,
year = {2025},
author = {Resta, E and Noviello, C and Peter, P and Graziano, G and Dalena, V and Caputi, A and Castellana, G and Riformato, G and Tafuri, S and Pierucci, P},
title = {Respiratory post-covid sequelae: the role of pulmonary function impairment, fatigue and obesity in dyspnea and the impact of SPA rehabilitation.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1080/17476348.2025.2516801},
pmid = {40470597},
issn = {1747-6356},
abstract = {BACKGROUND: Respiratory COVID-19 post-acute sequelae(PASC) may persist for extended periods following recovery.

METHODS: Patients with PASC who were referred for Salus Per Aquam(SPA)therapy were enrolled in the study. AIM: To categorize patients based on the presence of dyspnea and fatigue, with a specific focus on obesity, chronic respiratory conditions, and predictors of rehabilitation outcomes.

RESULTS: From July-November 2021, 327 consecutive patients were enrolled at the spa center. Among these, 31% had been previously hospitalized,5% had required noninvasive or invasive mechanical ventilation. Approximately one-third of the cohort underwent DLCO testing, which was abnormal in 56.3% of cases. Patients with impaired DLCO had significantly higher dyspnea rates compared to those with normal DLCO(88.9% vs. 64.3%,p < 0.0001).Dyspneic patients were more likely to have one or more comorbidities(p < 0.001),be obese(p = 0.005),and have a history of chronic respiratory disease (p = 0.0009).Patients reporting fatigue also had higher rates of dyspnea(91.2% vs. 61.5%,p < 0.0001), were more frequently obese(p = 0.03),had more comorbidities(p = 0.02),and had a greater history of hospitalization(p = 0.02).No improvement in dyspnea/fatigue was observed post-SPA treatment among patients with DLCO impairment and obese. However, patients with chronic respiratory conditions reported benefit.

CONCLUSIONS: Dyspnea in PASC is complex and multifactorial. The findings suggest that SPA rehabilitation may be particularly beneficial for alleviating fatigue and enhancing overall well-being in selected subgroups of patients with PASC.},
}

@article {pmid40470564,
year = {2025},
author = {Iannuccelli, C and Favretti, M and Dolcini, G and Di Carlo, M and Pellegrino, G and Bazzichi, L and Atzeni, F and Lucini, D and Varassi, G and Leoni, MLG and Fornasari, DMM and Conti, F and Salaffi, F and Sarzi Puttini, P and Di Franco, M},
title = {Fibromyalgia: one year in review 2025.},
journal = {Clinical and experimental rheumatology},
volume = {},
number = {},
pages = {},
doi = {10.55563/clinexprheumatol/buhd2z},
pmid = {40470564},
issn = {0392-856X},
abstract = {Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain, high prevalence, and a significant impact on quality of life. Despite extensive research, its pathogenesis and treatment remain only partially understood, driving continued investigation throughout 2024. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system has been linked to chronic stress responses and neuroinflammation, with neuroimaging and preclinical studies confirming altered pain and stress processing. Low-grade inflammation and metabolic disturbances, including cytokine imbalance and increased adipose tissue infiltration, further exacerbate symptoms. Alterations in the gut microbiota contribute to immune and emotional dysregulation. MRI studies continue to reveal brain changes that differentiate FM from other chronic pain disorders. Multi-omics approaches, including transcriptomic and metabolomic analyses, show promise as diagnostic biomarkers. Mitochondrial dysfunction also emerges as a key factor, since impaired energy metabolism seems to correlate with symptom severity. From a clinical perspective, recent studies have explored under-recognised aspects of FM, such as sexual and cognitive dysfunction, the role of gender, environmental exposures, and the disease's impact on relationships and family life. The differential diagnosis of FM and long COVID has ignited discussion about potential shared mechanisms. Conversely, residual pain in inflammatory diseases remains insufficiently addressed. Therapeutically, non-pharmacological strategies, particularly physical activity and psychosocial interventions, remain fundamental. Emerging areas such as non-invasive neuromodulation, psychedelic therapies, and the integration of technologies like virtual reality and artificial intelligence are opening new frontiers in treatment, patient care, and research. These advances underscore the multifactorial nature of FM and the need for personalised, interdisciplinary approaches.},
}

@article {pmid40470173,
year = {2025},
author = {Loli, A and Müller, JVC and de Azevedo, ES and Martins, RHG},
title = {Symptoms and Otorhinolaryngological Sequalae in Long Covid.},
journal = {International archives of otorhinolaryngology},
volume = {29},
number = {2},
pages = {1-6},
pmid = {40470173},
issn = {1809-9777},
abstract = {INTRODUCTION: After the pandemic caused by the coronavirus, many patients have presented remaining otorhinolaryngological symptoms, but most of them are unknown to health professionals.

OBJECTIVES: To characterize otorhinolaryngological symptoms and sequelae in hospitalized patients for Covid-19.

METHODS: We made a recall to patients hospitalized between April 2020 and April 2022 due to Covid-19. Demographic data, initial and remaining symptoms, days of hospitalization, intubation and/or tracheostomy, and vaccination data were collected.

RESULTS: 845 patients were hospitalized, 441 died, 404 patients were contacted by telephone, but only 109 responded to the questionnaire about initial and remaining otorhinolaryngological symptoms after 1.5 to 2 years of illness, 59 men and 50 women, with an average age of 58.61 years (20 to 94). Two study groups were composed: G 1 (n- 44; with remaining symptoms) and G 2 (n- 65; without remaining symptoms). 81% of patients in G1 and 67% of patients in G2 had been hospitalized for up to 20 days. Intubation occurred in 17 patients (G1-7; G2-10). Seven patients underwent tracheostomy. The most prevalent initial and remaining otorhinolaryngological symptoms, respectively, were dyspnea (68.8%; 14.6%), cough (65.1%; 11.92%), nasal obstruction (47.7%; 5.58%), smell dysfunction (44%; 11%), taste dysfunction (42%; 4.58%). Vaccination was reported by 54 patients (G1-21; G2-34).

CONCLUSIONS: Otorhinolaryngological symptoms were common in patients hospitalized for Covid-19, especially dyspnea, cough, nasal obstruction, smell, and taste dysfunction. Although there was a favorable long-term evolution, 40% of patients maintained permanent symptoms, such as smell and taste dysfunction and dizziness, unrelated to the vaccine doses.},
}

@article {pmid40470163,
year = {2025},
author = {Pike Welch, HL and Guest, G and Garba, H and Carrillo, GA and Damman, AM and Kibbe, WA},
title = {A community-engaged approach to developing common data elements: a case study from the RADx-UP Long COVID common data elements Task Force.},
journal = {JAMIA open},
volume = {8},
number = {3},
pages = {ooaf046},
pmid = {40470163},
issn = {2574-2531},
abstract = {OBJECTIVES: In response to requests from several Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) community-engaged research projects to include Long COVID common data elements (CDEs) in the existing RADx-UP CDEs, the RADx-UP Coordination and Data Collection Center (CDCC) leadership formed the Long COVID CDEs Task Force.

MATERIALS AND METHODS: The Task Force, composed mainly of community partners and RADx-UP project members, participated in various activities to evaluate the Long COVID CDEs fit for purpose from the Researching COVID to Enhance Recovery (RECOVER) program for RADx-UP use.

RESULTS AND DISCUSSION: The Task Force's efforts led to a compilation of lessons learned and the creation of a novel set of 28 CDEs that are appropriate for community-engaged research in Long COVID.

CONCLUSION: Utilization of standardized CDEs does not always work for the communities involved in the research, but creation of a community-involved task force can lead to a meaningful, rich set of CDEs.},
}

@article {pmid40470145,
year = {2025},
author = {Gallo González, V and López-Padilla, D and de Miguel Díez, J and Suárez Escudero, S and Ojeda Castillejo, E and Ji, Z and Puente Maestu, L},
title = {Long COVID-19 and longer sick leave: longitudinal study of economically active patients.},
journal = {ERJ open research},
volume = {11},
number = {3},
pages = {},
pmid = {40470145},
issn = {2312-0541},
abstract = {INTRODUCTION: Sick leave was one of the numerous consequences of the COVID-19 pandemic. Given the relevance of occupational status for any individual, the aim of the study was to evaluate the impact of persistent symptoms after active infection and determine factors associated with longer sick leaves (LSLs).

METHODS: This observational study focused on economically active patients attending a post-COVID outpatient clinic for persistence of symptoms or radiological alterations after active infection. The LSL temporal cut-off point was defined by the third tertile of total leave days. Median leave time was compared with the optimal sick leave time for any other viral pneumonia, estimated by the local Ministry of Employment. To determine factors associated with LSL, multivariate models were ultilised.

RESULTS: A total of 248 patients were included. The median sick leave time for the entire population was 53 days (interquartile range (IQR) 37.0-126.5), global sum of 30 169 days; the median optimal sick leave time was 21.9 days (IQR 19.7-25.9) (p<0.05). The third tertile cut-off point for LSL was 83 days and multivariate analysis showed a significant association with dyspnoea (OR 3.26, 95% CI 1.59-6.70, p=0.0001), while physical exercise of at least 10 min·day[-1] was significantly associated with shorter sick leave durations (OR 0.45, 95% CI 0.20-0.98, p=0.04).

DISCUSSION: COVID-19 sick leave was considerably longer than that stipulated for nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia. Long-COVID syndrome, especially dyspnoea, seems to be a very present factor in these patients' inability to work.},
}

@article {pmid40469928,
year = {2025},
author = {Honchar, O and Ashcheulova, T and Bobeiko, A and Blazhko, V and Khodosh, E and Matiash, N and Syrota, V},
title = {12-Month trajectories of physical and mental symptom scores after COVID-19 hospitalization and their role in predicting "very long" COVID.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1568291},
pmid = {40469928},
issn = {2673-6861},
abstract = {BACKGROUND: Long COVID syndrome (LCS) represents a significant global health challenge due to its wide-ranging physical and cognitive symptoms that persist beyond 12 months in a substantial proportion of individuals recovering from SARS-CoV-2 infection. Developing tools for predicting long-term LCS persistence can improve patient management and resource allocation.

OBJECTIVE: To evaluate the natural dynamics of symptoms over 12 months following hospitalization for COVID-19 and to establish the utility of survey-based symptoms assessment for predicting LCS at one year.

METHODS: This prospective observational study included 166 hospitalized COVID-19 survivors who were evaluated pre-discharge and followed up at 1, 3, and 12 months. Assessments included surveys including physical and mental symptom scales (e.g., EFTER-COVID, SBQ-LC, PCFS, MRC Dyspnea, CAT, CCQ, and HADS) and machine learning modeling to predict LCS persistence at 12 months.

RESULTS: LCS symptoms were reported by 76% of patients at three months and 43% at 12 months. Physical symptom scores, particularly EFTER-COVID and PCFS, consistently differentiated LCS and LCS-free cohorts. CAT outperformed other respiratory scales in its discriminatory ability, while HADS subscales showed limited predictive value. Younger patients (<40 years) demonstrated faster recovery, whereas older patients (>60 years) exhibited persistent symptoms across respiratory and cognitive domains. A machine learning model combining EFTER-COVID, SBQ-LC, CAT, and MRC Dyspnea scores achieved 91% predictive accuracy for LCS persistence at 12 months.

CONCLUSION: Comprehensive survey-based symptoms assessment at three months post-discharge provides a practical and cost-effective tool for prediction of the long COVID persistence at 12 months, supporting targeted rehabilitation strategies.},
}

@article {pmid40469004,
year = {2025},
author = {Faux-Nightingale, A and Saunders, B and Burton, C and Chew-Graham, CA and Somayajula, G and Twohig, H and Welsh, V},
title = {Perceptions and Significance of Long Covid Diagnoses From the Perspectives of Children and Young People With Long Covid, Their Parents and Professionals.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {3},
pages = {e70318},
doi = {10.1111/hex.70318},
pmid = {40469004},
issn = {1369-7625},
support = {//This study presents independent research funded by the NIHR School for Primary Care Research (Grant Reference Number 517) and the NIHR West Midlands Clinical Research Network. C.B. is funded by a National Institute for Health Research (NIHR) Clinical Lectureship. V.W. is part-funded by WM ARC./ ; },
mesh = {Humans ; Child ; *COVID-19/diagnosis/psychology ; Adolescent ; Female ; *Parents/psychology ; Focus Groups ; Interviews as Topic ; Male ; Qualitative Research ; SARS-CoV-2 ; *Health Personnel/psychology ; },
abstract = {INTRODUCTION: Long Covid, the patient-preferred term, describes symptoms persisting after an acute Covid-19 infection. Understanding the importance and meaning of a Long Covid diagnosis to children and young people (CYP), their families and professionals associated with their care can give insight into the way that these diagnoses are used across these groups to support care and needs of the patient. This study explores the meaning and importance of a Long Covid diagnosis from the perspectives of CYP with Long Covid, their parents and relevant professionals.

METHODS: CYP and their parents or carers were invited to interview following participation in an initial cohort study. Professionals with experience working with CYP with Long Covid were invited to participate in a focus group. Interviews were carried out with four CYP with Long Covid (all female, aged 10-17 years); parents were present at three interviews. Seven professionals with experience in the care of CYP or Long Covid participated in one of two focus groups. Data were analysed thematically using constant comparison techniques.

RESULTS: The three main themes presented are as follows: the importance of receiving a diagnosis, diagnosis facilitates access to support and perspectives of discordance between family and professionals. The diagnosis of Long Covid has different meanings and significance for parents and professionals. Families described the diagnosis as a legitimisation of their experiences and a way to access support, but professionals questioned some of the ways families use the diagnosis, focusing instead on appropriate treatment according to CYP's needs.

CONCLUSION: For families, Long Covid diagnoses are important for validating and legitimising symptoms, removing uncertainty, and supporting access and participation, particularly in school. While these uses differ from those of professionals, understanding the importance of a Long Covid diagnosis to families may ensure effective communication, negotiation of an acceptable management plan, and ongoing support for this group.

Patients and the public contributed throughout this project and had input on the study design, topic guides, and dissemination of findings.},
}

Humans
Child
*COVID-19/diagnosis/psychology
Adolescent
Female
*Parents/psychology
Focus Groups
Interviews as Topic
Male
Qualitative Research
SARS-CoV-2
*Health Personnel/psychology

@article {pmid40467399,
year = {2025},
author = {Chia-Ying, L and Hsin-Sui, H and Chun-Hsing, L},
title = {Long COVID Clinical Features in Northern Taiwan: Insights from a Single Medical Center Study.},
journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmii.2025.05.006},
pmid = {40467399},
issn = {1995-9133},
abstract = {BACKGROUND: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID, encompasses persistent symptoms following acute COVID-19, impacting quality of life. This study delineates the epidemiology, clinical presentation, and quality of life effects of long COVID in Northern Taiwan using data from the 2021 COVID-19 home quarantine telemedicine care system.

METHODS: A prospective cohort of 625 PCR-confirmed COVID-19 patients, diagnosed between April and October 2021, was monitored for 3-6 months post-recovery. We assessed persistent symptoms, quality of life via the EQ-5D questionnaire, and risk factors including age, sex, vaccination status, household clusters, and hospitalization.

RESULTS: Among participants, 22 % reported malaise, 14 % dyspnea, and 7 % cough as persistent symptoms. Older age (≥65 years) and hospitalization were associated with greater quality of life impairment across EQ-5D domains (OR = 2.72, 95 % CI: 1.60-4.63, p < 0.001). Vaccinated individuals (7 %) showed a non-significant trend toward better EQ-5D scores (p = 0.116, 95 % CI: 0.05 to 0.20).

CONCLUSIONS: Older age and hospitalization significantly predict long-term quality of life impairment in long COVID. Targeted interventions for these groups and robust post-recovery support are essential. Limitations include reliance on self-reported data, a low vaccination rate (7 %), a 3-6 months follow-up, and a single-center design, which may limit generalizability. Multi-center studies with longer follow-ups and objective biomarkers are needed to enhance further understanding.},
}

@article {pmid40465774,
year = {2025},
author = {Salmam, I and Dubé, MO and Zahouani, I and Ramos, A and Desmeules, F and Best, KL and Roy, JS},
title = {The impact of long COVID on physical and cardiorespiratory parameters: A systematic review.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0318707},
doi = {10.1371/journal.pone.0318707},
pmid = {40465774},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/physiopathology/complications ; SARS-CoV-2 ; Respiratory Function Tests ; Adult ; Exercise Tolerance ; },
abstract = {BACKGROUND: Since the emergence of COVID-19, millions worldwide have continued to experience persistent symptoms months after infection. Among these, physical and cardiorespiratory impairments are frequently reported, but remain poorly understood. This systematic review aimed to identify and synthesize evidence regarding physical and cardiorespiratory impairments in individuals with long COVID, defined as symptoms persisting for at least three months post-infection.

METHODS AND FINDINGS: A structured search was conducted across the MEDLINE, Embase, CINAHL, and Web of Science databases to identify cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. Twenty-two studies involving 3,041 adults with long COVID were included. Critical appraisal using the JBI-APT indicated that most studies had clear inclusion criteria (17/22), well-defined study populations (17/22), and valid exposure measurements (16/22), though confounding factors were often unaddressed (9/22 unclear or not reported). Findings indicate that while adults with long COVID displayed normal pulmonary function at rest, including Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Total Lung Capacity (TLC), and resting Arterial oxygen saturation (SpO2), significant impairments in exercise capacity were identified. Notably, all studies assessing the 6-minute walk test (6MWT) reported reduced distances, consistently falling below the 50th percentile of normative values. Additionally, VO₂peak was decreased in most studies (7/10), falling below 80% of the predicted value, indicating impaired aerobic capacity. Lower Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) values were observed in three out of six studies, with values below 75% of predicted, suggesting impaired gas exchange efficiency during exertion.

CONCLUSION: Despite preserved resting lung function, these findings highlight significant physical deconditioning in Long COVID adults, with substantial reduction in exercise capacity. Routine assessments should include more sensitive measures, such as the 6MWT and VO₂peak, to detect subtle exercise limitations, even in patients with normal resting SpO₂, to better inform rehabilitation interventions.},
}

Humans
*COVID-19/physiopathology/complications
SARS-CoV-2
Respiratory Function Tests
Adult
Exercise Tolerance

@article {pmid40465195,
year = {2025},
author = {Glass, KA and Giloteaux, L and Zhang, S and Hanson, MR},
title = {Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Clinical and translational medicine},
volume = {15},
number = {5},
pages = {e70346},
doi = {10.1002/ctm2.70346},
pmid = {40465195},
issn = {2001-1326},
mesh = {Humans ; Male ; *Fatigue Syndrome, Chronic/physiopathology/metabolism ; *Extracellular Vesicles/metabolism ; *Endoplasmic Reticulum Stress/physiology ; Adult ; Proteomics/methods ; *Energy Metabolism/physiology ; *Exercise/physiology ; *Complement System Proteins/metabolism ; Middle Aged ; },
abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness characterized by post-exertional malaise (PEM), a worsening of symptoms following exertion. The biological mechanisms underlying PEM remain unclear. Extracellular vesicles (EVs) play a key role in cell-cell communication and may provide insight into ME/CFS pathophysiology post-exertion. Emerging evidence suggests similarities between ME/CFS and Long COVID, including PEM and overlapping immune and metabolic dysfunctions, highlighting the need for deeper mechanistic understanding.

METHODS: This study explores the EV proteome response to exercise in 10 males with ME/CFS and 12 well-matched sedentary male controls. Participants underwent a maximal cardiopulmonary exercise test, and plasma samples were collected at baseline, 15 min, and 24 h postexercise. EVs were isolated from plasma using size-exclusion chromatography and characterized with nanoparticle tracking analysis. EV protein abundance was quantified with untargeted proteomics (nanoLC-MS/MS). Comprehensive analyses included differential abundance, pathway enrichment, protein-protein interaction networks, and correlations between EV protein dynamics and clinical or exercise physiology data.

RESULTS: ME/CFS patients exhibited many significantly altered EV proteomic responses compared with controls, including downregulation of TCA cycle-related proteins and upregulation of complement system proteins at 15 min postexercise. Changes in proteins involved in protein folding and the endoplasmic reticulum (ER) stress response during recovery were highly correlated with PEM severity, highlighting their potential as therapeutic targets. EV protein changes postexercise were also associated with disease severity and unrefreshing sleep. Correlations between EV protein levels and the exercise parameters VO₂ peak and ventilatory anaerobic threshold were observed in controls but were absent in ME/CFS patients, suggesting disrupted EV-mediated physiological processes.

CONCLUSIONS: ME/CFS patients exhibit a maladaptive EV proteomic response to exercise, characterized by metabolic impairments, immune overactivation, and ER stress response dysregulation. These findings provide insight into the molecular basis of PEM and suggest promising targets for improving recovery and energy metabolism in ME/CFS.

KEY POINTS: EVs were isolated from plasma of ME/CFS patients and healthy controls at baseline, and 15 min and 24 h postexercise. Untargeted proteomics revealed dysregulation in energy metabolism, the complement system, and the endoplasmic reticulum stress response. Changes in EV protein levels postexercise are associated with post-exertional malaise. These findings suggest promising therapeutic targets for post-exertional malaise and ME/CFS pathophysiology.},
}

Humans
Male
*Fatigue Syndrome, Chronic/physiopathology/metabolism
*Extracellular Vesicles/metabolism
*Endoplasmic Reticulum Stress/physiology
Adult
Proteomics/methods
*Energy Metabolism/physiology
*Exercise/physiology
*Complement System Proteins/metabolism
Middle Aged

@article {pmid40465108,
year = {2025},
author = {Fang, C and Dobie, C and Ketkar, A and Verduzco-Gutierrez, M and Fadda, G and Bocage, C and Teng, CCJ and Perez, R and Brunk-Grady, M and Glasser, L and Dube, C and Breslin, N and Willey, V},
title = {Evaluating the Impact of Age and Comorbidities on COVID-19 Outcomes and Healthcare Costs: A Comparative Analysis of Immunocompromised and General Populations in the United States (EON-US).},
journal = {Infectious diseases and therapy},
volume = {},
number = {},
pages = {},
pmid = {40465108},
issn = {2193-8229},
abstract = {INTRODUCTION: The COVID-19 public health emergency (PHE) ended in May 2023, but limited information exists on the continued risk of severe COVID-19 among the immunocompromised (IC) population and those with certain chronic medical conditions (CMCs). This study aimed to assess the risk of moderate/severe COVID-19 and compare associated healthcare resource utilization (HCRU) and costs for IC vs. general populations, with a focus on increasing age and CMC burden in the IC population.

METHODS: This retrospective observational cohort study analyzed claims from the Healthcare Integrated Research Database (HIRD[®]) for individuals with a COVID-19 diagnosis or positive test between March 2023 and February 2024. Patients were followed until the study's end, disenrollment, or death. Propensity scores were calculated using binomial logistic regression to adjust for confounding when comparing the IC and general population groups. The IC cohort was divided into five subgroups based on age (
RESULTS: The IC cohort (N = 8025) was older and had a higher comorbidity burden than the general population (N = 458,163), which was balanced after matching (N = 7410 each). The IC cohort had a significantly higher rate of severe COVID-19 vs. the general population (9.5% vs. 1.1%; p < 0.001), but there was no difference after matching (8.9% vs. 8.7%; p = 0.772). Older age and increasing number of CMCs led to a significantly higher proportion of severe COVID-19. Compared to the general population, the IC cohort had significantly higher inpatient all-cause and COVID-19-related HCRU and costs, except within the matched analysis where COVID-19-related hospitalizations were not significantly different between the groups.

CONCLUSIONS: Severe COVID-19 continued to disproportionately affect IC individuals after the PHE was lifted. Additionally, our matched results identified a subset of the general population with high baseline comorbidity burden and risk similar to the matched IC cohort for severe COVID-19.},
}

@article {pmid40464778,
year = {2025},
author = {Barbosa, NL and Rangel Agra Oliveira, T and Nóbrega, LD and Araújo, TTF and Bezerra, SRS and Oliveira, GM and Do Nascimento, RM and Nogueira, PAMS and Tomaz, AF and Fernandes, ATDNSF},
title = {Prevalence and characteristics of respiratory and cardiovascular sequelae in post-COVID-19 syndromes: a scoping review.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1080/17476348.2025.2515992},
pmid = {40464778},
issn = {1747-6356},
abstract = {INTRODUCTION: Post acute and Long COVID-19 are a public health issue, marked by persistent respiratory and cardiovascular symptoms such as dyspnea and palpitations. These complications often extend beyond the acute phase, affecting even individuals with mild or moderate COVID-19. This article reviews the clinical impact of long COVID-19 and emphasizes the need for a multidisciplinary approach to management.

AREAS COVERED: A comprehensive literature search was conducted through PubMed, Medline, CINAHL, SciELO, and LILACS to identify studies published up to 28 October 2024, reporting on respiratory and cardiovascular sequelae in long COVID-19. This review examines the prevalence and characteristics of persistent symptoms such as dyspnea, cough, and palpitations, as well as the associated risk factors and assessment methods.

EXPERT OPINION: Long COVID-19 represents a significant healthcare challenge, underscoring the need for standardized protocols for diagnosis and treatment. A multidisciplinary approach is crucial to address the diverse symptoms of affected patients. Future research should focus on understanding the underlying pathophysiology, and developing targeted therapeutic strategies to improve patient outcomes.},
}

@article {pmid40464158,
year = {2025},
author = {Lak, V and Sjöland, H and Adiels, M and Lundberg, CE and Robertson, J and Åberg, M and Alex, C and Lindgren, M and Rosengren, A},
title = {Preexisting symptoms increase the risk of developing long COVID during the SARS-CoV-2 pandemic.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.20102},
pmid = {40464158},
issn = {1365-2796},
support = {2019-00193//Swedish Research Council/ ; 2020-05792//Swedish Research Council/ ; 2021-06525//Swedish Research Council/ ; 2023-02144//Swedish Research Council/ ; 2021-0345//Swedish Heart and Lung Foundation/ ; 2024-0678//Swedish Heart and Lung Foundation/ ; 2021-00304//Forskningsrådet om Hälsa, Arbetsliv och Välfärd/ ; ALFGBG-966211//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-1006439//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-942707//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-971608//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; ALFGBG-943008//Grants from the Swedish state under an agreement concerning research and education of doctors/ ; },
abstract = {BACKGROUND: Long COVID is defined as otherwise unexplained symptoms following a SARS-CoV-2 infection.

OBJECTIVE: To examine the prevalence of preexisting symptoms compatible with long COVID in individuals with a diagnosis of long COVID.

METHODS: This retrospective, observational study included the adult population (aged 18 years and older) in Region Västra Götaland, with at least one recorded healthcare contact between January 1, 2020, and November 30, 2023, from a regional database comprising all levels of healthcare contacts. Data on long COVID, relevant symptoms before and after the pandemic started (2016-2023), and SARS-CoV-2 infection status were extracted using the International Classification of Diseases version 10 (ICD-10) codes. Individuals who had been hospitalized due to a SARS-CoV-2 infection were considered separately.

RESULTS: Out of 1,415,885 individuals, 9202 (0.6%) had been diagnosed with long COVID. Among the non-hospitalized individuals, the record of at least one of the relevant symptoms was more common in those with long COVID compared to those without it (57.6% vs. 36.3% for men and 71.6% vs. 50.4% for women), already before January 1, 2020. Among individuals with any relevant symptom, the odds ratios (ORs) of having long COVID were OR = 2.28 (95% confidence interval [CI] = 2.10-2.48) for men and OR = 2.32 (95% CI = 2.18-2.48 for women) after adjusting for age group, obesity, asthma, and anxiety, compared with individuals without any relevant symptom.

CONCLUSIONS: Individuals diagnosed with long COVID had more healthcare contacts for relevant symptoms even before the pandemic compared to individuals without long COVID.},
}

@article {pmid40463782,
year = {2025},
author = {Farr, E and Esterov, D and Kassmeyer, BA and Lennon, RJ and Bergquist, TF},
title = {Demographics, Clinical Characteristics, and Outcomes of a Post-Coronavirus-19 Sample After Cognitive Rehabilitation: A Case Series.},
journal = {Archives of rehabilitation research and clinical translation},
volume = {7},
number = {1},
pages = {100409},
pmid = {40463782},
issn = {2590-1095},
abstract = {The Coronavirus-19 pandemic has infected millions of people, resulting in ongoing symptoms now described as post-acute sequelae of SARS-COV2 infection (PASC). Persistent neurologic and behavioral sequelae including fatigue, depression, anxiety, sleep disorders, headache, memory loss, and cognitive complaints are common. Although there is increasing evidence related to treatment of physical symptoms such as fatigue through physical rehabilitation practices, to date there is very limited evidence about the efficacy of various treatment regimens directed at nonphysical symptoms such as cognitive concerns and behavioral sequelae. This case series discusses a series of 13 patients with PASC who underwent individualized multidisciplinary outpatient cognitive rehabilitation at a quaternary medical center. In this patient population, the median age was 46 years (Q1, Q3: 41, 50), 77% were women, and 85% were White. The median time from infection to treatment was 229 days (Q1, Q3: 117, 367) and median length of stay in the program was 4.9 months (Q1, Q3: 3.1, 6.3). A history of depression and anxiety was found in 38% and 46% of this population, respectively. On admission and at discharge, the Mayo-Portland Adaptability Inventory-4 Participation Index, the Satisfaction with Life Scale, the Patient Health Questionnaire-9, and the Neurobehavioral Symptom Inventory-22 were completed. After individualized outpatient cognitive therapy, no clear benefit was seen in any of the outcome measures. The ongoing investigation is important to better understand which approaches will benefit these patients.},
}

@article {pmid40463044,
year = {2025},
author = {Amer, HM and Shamseldin, MM and Faber, S and Eltobgy, M and Webb, A and El-Mergawy, R and Chamblee, M and Perez, R and Whitham, O and Badr, A and Gupta, G and Omran, J and Bissel, D and Yount, J and Cormet-Boyaka, E and Boyaka, PN and Li, J and Zhang, X and Peeples, ME and Mahesh, KC and Pietrzak, M and Seveau, S and Kokiko-Cochran, O and Amer, M and Barrientos, RM and Schamess, A and Oltz, E and Amer, AO},
title = {AI-based decoding of long covid cognitive impairments in mice using automated behavioral system and comparative transcriptomic analysis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.14.654036},
pmid = {40463044},
issn = {2692-8205},
abstract = {Long COVID (LC) following SARS-CoV-2 infection affects millions of individuals world-wide and manifests with a variety of symptoms including cognitive dysfunction also known as "brain fog". This is characterized by difficulties in executive functions, planning, decision-making, working memory, impairments in complex attention, loss of ability to learn new skills and perform sophisticated brain tasks. No effective treatment options currently exist for LC-related cognitive dysfunction. Here, we use the IntelliCage, which is an automated tracking system of cognitive functions, following SARS-CoV-2 infection in mice, measuring the ability of each mouse within a group to perform tasks that mimic complex human behaviors, such as planning, decision-making, cognitive flexibility, and working memory. Artificial intelligence and machine learning analyses of the tracking data classified LC mice into distinct behavioral categories from non-infected control mice, permitting precise identification and quantification of complex cognitive dysfunction in a controlled, replicable manner. Importantly, we find that brains from LC mice with cognitive dysfunction exhibit transcriptomic alterations similar to those observed in humans suffering from LC-related cognitive impairments, including altered expression of genes involved in learning, executive functions, synaptic functions, neurotransmitters and memory. Together, our findings establish a validated murine model and an automated unbiased approach to study LC-related cognitive dysfunction for the first time, and providing a valuable tool for screening potential treatments and therapeutic interventions.},
}

@article {pmid40462722,
year = {2025},
author = {Nielssen, I and Olson, S and Goulding, S and Bohja, S and Yu, M and Paguirigan, R and McEntee, E and Bruce, M and McKenzie, N and Fairie, P and Santana, MJ},
title = {What Are the Barriers and Supports to a Return to Health From Long COVID? A Qualitative Study Designed, Developed, and Conducted by Individuals With Lived Experience of Long COVID.},
journal = {Qualitative health research},
volume = {},
number = {},
pages = {10497323251337566},
doi = {10.1177/10497323251337566},
pmid = {40462722},
issn = {1049-7323},
abstract = {Long COVID is a debilitating and persistent illness that affects individuals in multiple and dynamic ways. Because of the significant physical, emotional, and economic impacts long COVID holds on individuals, their families, and society more broadly, it is imperative that a multi-faceted approach is taken to the long COVID research that aims to improve outcomes for those affected. Expertise about the barriers and supports to accessing appropriate, patient-centered care is best provided by those with lived experience. A Patient and Community Engagement Research (PaCER) team of student researchers, all with lived experience of long COVID, conducted a qualitative study to understand barriers and supports to a return to health for those living with long COVID. This online study was informed by Canada-wide participants all living with long COVID. Patient experience and perspective data were collected through peer-to-peer focus groups and semi-structured interviews. The team used a thematic and a thematic and narrative analysis approach to identify six themes: Challenges Within Medical Systems to Keep Pace With Novel Condition, Impact of Long COVID Condition on Mental Well-Being, Money Matters, Managing Personal Energy Capacity, Resources and Supports for Long COVID Care and Recovery, and Disregard Participants Felt Toward Their Health and Well-Being. They identified 21 subthemes. This patient-directed study yielded essential recommendations to supporting a return to health for those living with long COVID to enable them to re-engage with their previous family, social, employment, and other relational activities. In addition to demonstrating more inclusive approaches to including long COVID patients in the research that impacts them, the study results can inform more appropriate person-centered healthcare, planning, and policy for those living with, and for those who will be living with, long COVID going forward.},
}

@article {pmid40460818,
year = {2025},
author = {Drobinska, N and Nehme, M and Assal, F and Laffitte, E and Guessous, I and Lascano, AM},
title = {Small Fiber Neuropathy in Long COVID: a cohort study with multimodal assessment and follow-up.},
journal = {European neurology},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000546015},
pmid = {40460818},
issn = {1421-9913},
abstract = {BACKGROUND: Given the increasing number of patients suffering from pain associated with dysautonomic symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we aimed to estimate the occurrence of small fiber neuropathy (SFN) in a cohort of long coronavirus disease 19 (COVID-19) patients reporting post-infectious neuropathic pain.

METHODS: The study cohort included 18 patients suffering from symptoms suggestive of SFN (Neuropathic pain score DN4 ≥4) appearing after or during SARS-CoV-2 infection and lasting ≥90 days. Patients underwent multimodal SFN evaluation by skin biopsy, quantitative sensory testing (QST), laser evoked potential (LEP) recording and Electrochemical skin conductance (ESC; Sudoscan).

RESULTS: Out of 18 patients, 17 were analyzed. Participants' ages averaged 44+/-9 years, with 94% females. Fourteen (82%) had abnormal skin biopsy results. Notably, 12/17 (70%) patients presented with autonomic complaints, all of whom had abnormal skin biopsy results. At 6 months follow-up, 10/17 patients reported a subjective improvement in pain and/or dysautonomia with or without symptomatic pharmacological or non-pharmacological treatment. In our cohort, QST showed the highest sensibility (79%) and specificity (67%), followed by LEP (sensibility 71%, specificity 67%). ESC showed poor reliability in the screening of SFN with a sensibility of 7% and specificity of 50%.

CONCLUSION: The results of our study suggest that SFN may develop during or shortly after SARS-CoV-2 infection, provoking disabling sensory and dysautonomic symptoms that tend to persist for more than 6 months. Furthermore, our findings imply that non-invasive exams, are a useful complement to biopsy in the diagnostic process of SFN.},
}

@article {pmid40458645,
year = {2025},
author = {Visconti, NRG and Rocha, NN and Nascimento, GS and Menário, CVB and Silva, JD and Martins, CM and Caruso-Neves, C and Cruz, FF and Rocco, PRM and Mello, FCQ and Lapa-E-Silva, JR},
title = {Elevated adipokines and myokines are associated with fatigue in long COVID patients.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1547886},
pmid = {40458645},
issn = {2296-858X},
abstract = {BACKGROUND: Persistent fatigue is one of the most common and debilitating symptoms experienced by patients recovering from COVID-19, contributing significantly to the burden of "long COVID" or post-COVID-19syndrome. However, the underlying pathophysiological mechanisms remain inadequately understood. Few studies have examined the association between fatigue and pulmonary or cardiac function, systemic biomarkers, or morphological changes in the lungs and diaphragm. Furthermore, the potential influence of vaccination on the persistence of fatigue has not been fully explored. This study aims to identify mechanisms contributing to post-COVID-19 fatigue.

METHODS: This prospective cohort study assessed clinical, laboratory, pulmonary, and cardiac parameters, as well as diaphragm ultrasound and pulmonary function, in patients with and without fatigue at least 4 months after discharge from hospitalization due to COVID-19.

RESULTS: Of 88 patients evaluated, 34% reported new or worsening fatigue after recovering from COVID-19. Demographic characteristics, comorbidities, and vaccination status were similar between fatigued and non-fatigued groups. However, ICU admission during the acute phase of illness emerged as a significant risk factor for fatigue (OR 2.65; 95% CI, 1.03-6.94) in multivariable analysis. No significant differences were observed in lung function, diaphragm or lung ultrasound findings, or left ventricular systolic function between groups. Fatigue was associated with significantly elevated serum levels of myostatin and irisin, markers of muscle metabolism. Additionally, patients experiencing fatigue reported poorer functional capacity and significantly reduced quality of life, with lower scores in multiple domains of the SF-36 questionnaire, including general health, vitality, and mental health.

CONCLUSION: Post-COVID-19 fatigue is strongly associated with prior ICU admission and elevated levels of myostatin and irisin, implicating potential myopathic mechanisms in its persistence. The profound impact of fatigue on functional capacity and quality of life highlights the urgent need for further research to elucidate its pathophysiology and develop targeted therapeutic strategies. This study provides critical insights into the interplay between systemic and organ-specific factors contributing to fatigue, offering a foundation for future interventions to improve outcomes in patients with long COVID.},
}

@article {pmid40458610,
year = {2025},
author = {Liao, M and Cai, J and Zhu, F and Lan, Y and Xu, T and Guo, J and Xue, Q and Wen, Y and Zou, F and Zhang, Y and Zhang, S and Yan, Y and Ai, J and Cui, J and Zhang, W},
title = {Meta-transcriptomics Reveals Dysbiosis of the Respiratory Microbiome in Older Adults with Long COVID.},
journal = {Research (Washington, D.C.)},
volume = {8},
number = {},
pages = {0720},
pmid = {40458610},
issn = {2639-5274},
abstract = {Limited research has investigated the connection between long COVID (LC) and the respiratory microbiome, particularly in older adults. This study aimed to characterize the respiratory microbiome of older LC patients (with an average age of 65 years old), through meta-transcriptomic sequencing of 201 individual samples. Marked differences in microbial diversity were observed between LC and non-LC patients, including disruptions in both pathogenic bacteria and fungi. Importantly, viral taxa, such as Herpes simplex virus type 1 and Human coronavirus 229E, were more frequently detected in LC patients, indicating the vulnerability of LC patients to viral infections. Functional annotation at the expression level revealed notable differences in microbial metabolism with alterations observed in pathways related to tryptophan-serotonin metabolism in LC patients. These findings underscore the altered microbial landscape, especially in older adults who developed LC, and fill the gap for the potentially clinical roles played by the respiratory microbiome.},
}

@article {pmid40458265,
year = {2025},
author = {Sasso, EM and Eaton-Fitch, N and Smith, P and Muraki, K and Marshall-Gradisnik, S},
title = {Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1582967},
pmid = {40458265},
issn = {2296-889X},
abstract = {INTRODUCTION: Long COVID is a multisystemic condition that includes neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, independent of the severity or duration of the acute SARS-CoV-2 infection. Dysfunctional Transient Receptor Potential Melastatin 3 (TRPM3) ion channels are associated with the pathophysiology of long COVID due to reduced calcium (Ca[2+]) influx, negatively impacting cellular processes in diverse systems. Accumulating evidence suggests the potential therapeutic benefits of low-dose naltrexone (LDN) for people suffering from long COVID. Our study aimed to investigate the efficacy of LDN in restoring TRPM3 ion channel function in natural killer (NK) cells from long COVID patients.

METHODS: NK cells were isolated from nine individuals with long COVID, nine healthy controls, and nine individuals with long COVID who were administered LDN (3-4.5 mg/day). Electrophysiological experiments were conducted to assess TRPM3 ion channel functions modulated by pregnenolone sulfate (PregS) and ononetin.

RESULTS: The findings from this current research are the first to demonstrate that long COVID patients treated with LDN have restored TRPM3 ion channel function and validate previous reports of TRPM3 ion channel dysfunction in NK cells from individuals with long COVID not on treatment. There was no significant difference in TRPM3 currents between long COVID patients treated with LDN and healthy controls (HC), in either PregS-induced current amplitude (p > 0.9999) or resistance to ononetin (p > 0.9999).

DISCUSSION: Overall, our findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca[2+] influx necessary for homeostatic cellular processes.},
}

@article {pmid40458104,
year = {2025},
author = {Morera, M and Arévalo, A and Garriga, C and Corral-Magaña, M and García-Arqué, MC and Gragea-Nocete, M and Pérez Díaz, C and Roca, R and Llistosella, M},
title = {Assessing a multicomponent intervention to improve quality of life in individuals with Long COVID (COVIDL/MIQoL): study protocol for a randomized controlled trial.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1604971},
pmid = {40458104},
issn = {2296-2565},
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/psychology ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Female ; Male ; Adult ; Middle Aged ; },
abstract = {INTRODUCTION: The impact of Long COVID on the quality of life of affected individuals is significant, therefore, the aim of this study is to analyse the effectiveness of the multicomponent intervention protocol to improve quality of life in individuals with Long COVID.

METHODS: A randomized controlled trial with two parallel arms will be conducted. Individuals diagnosed with Long COVID, but without any severe mental disorders, will be recruited. The sample size is estimated to be around 54 participants per group. A psychologist and a physiotherapist will carry out the intervention between January and March 2025. Participants will receive specific training in psycho-education and physical rehabilitation consisting of 18 sessions, to be held twice a week. Data collection will start in January 2025 and will finish in October 2025. Data will be collected: at baseline, before the intervention (T0); after 9 weeks, post-intervention (T1); and after 24 weeks, follow-up (T2), and will assess quality of live, well-being, anxiety, depression resilience, fatigue, and physical activity. An intention-to-treat analysis will be performed and the effect size will be calculated using Cohen's d. All statistical analyses will be performed using R software version 4.2.2, with a 95% confidence level and a statistical significance level of p < 0.05.

DISCUSSION/CONCLUSION: The results will be disseminated to individuals with Long COVID and their families throughout their primary health care center. Healthcare professionals will receive specific training to be able to develop and implement the intervention. In addition, the results will be disseminated to the scientific community via conferences and publications.

CLINICAL TRIAL REGISTRATION: https://register.clinicaltrials.gov/prs/beta/studies/S000ENW100000080/recordSummary, Identifier NCT06492590.},
}

Humans
*Quality of Life/psychology
*COVID-19/psychology
Randomized Controlled Trials as Topic
SARS-CoV-2
Female
Male
Adult
Middle Aged

@article {pmid40457068,
year = {2025},
author = {Bonnefoy, PB and Pascal, P and Ceyrat, Q and Burg, S and Razzouk-Cadet, M and Moreau Triby, C and Biancheri Mounicq, I and Bourre, JC and Salaun, PY and Le Roux, PY},
title = {Interest of ventilation/perfusion SPECT/CT in patients with post-COVID condition: a multicenter observational study.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {40457068},
issn = {1619-7089},
}

@article {pmid40455450,
year = {2025},
author = {Guilliams, KP},
title = {The Importance of Playing the Long Game With Long COVID and Long-Term Hospital Recovery.},
journal = {JAMA network open},
volume = {8},
number = {6},
pages = {e2512495},
doi = {10.1001/jamanetworkopen.2025.12495},
pmid = {40455450},
issn = {2574-3805},
}

@article {pmid40454660,
year = {2025},
author = {Friedly, JL and Roman, J and Long, J and Grewal, M and Chopra, A and Bender, J and Gentile, N and Knowles, LM and Herring, T and O'Loughlin, K and Rivera, N},
title = {The healing role of music and arts in long COVID: A patient perspective.},
journal = {PM & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.13430},
pmid = {40454660},
issn = {1934-1563},
support = {1U18HS029905-01//Agency for Healthcare Research and Quality/ ; },
}

@article {pmid40454145,
year = {2025},
author = {Mainous, AG and Bao, S and Goldman, M},
title = {Editorial: Long COVID: pathogenesis, diagnosis and clinical management.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1615692},
pmid = {40454145},
issn = {2296-858X},
}

@article {pmid40453253,
year = {2025},
author = {Boorle, NVLD and Kurra, NC and Gandrakota, N and Modi, K and Sudireddy, K and Irfan, SA and Jain, A and Parikh, PA and Jillella, D},
title = {Central Nervous System Manifestations of Long COVID: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83247},
pmid = {40453253},
issn = {2168-8184},
abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been one of the most widespread and devastating global pandemics, impacting hundreds of millions of people worldwide. After the cessation of active infection, the disease continues to have a disabling impact due to the persistence of fatigue, brain fog, anxiety, and depression - among the most common symptoms. This study explores the progression of neurological symptoms over 12 months and beyond following an initial diagnosis of COVID-19. Through an electronic search of eligible studies from PubMed, the Cochrane Trial Register, and Google Scholar, 10 studies were included for qualitative analysis. The systematic review highlights the similarities and differences in findings across the included studies. Olfactory dysfunction was prevalent in 0.9%-51% of individuals, and taste impairment was observed in 1.1%-21.3%. At 12 months, anxiety was more prevalent (3.5%-29%) than depression (3.5%-26%). Fatigue was the predominant neurocognitive complaint in 56% of individuals with severe COVID-19. Nearly half of individuals reported sleep difficulties. Memory impairment, followed by headaches and dizziness, also constitutes neurocognitive symptoms reported at 12 months. Our study found that there is a significant neurological burden one year following the diagnosis of COVID-19. Further studies exploring the pathological mechanisms of long-term COVID-19 are necessary to better delineate the mechanisms behind several long-term neurological manifestations of COVID-19.},
}

@article {pmid40450635,
year = {2025},
author = {Oh, S and An, S and Park, K and Lee, S and Han, YM and Koh, SJ and Lee, J and Gim, H and Kim, D and Seo, H},
title = {Gut Microbial Signatures in Long COVID: Potential Biomarkers and Therapeutic Targets.},
journal = {Infectious diseases and therapy},
volume = {},
number = {},
pages = {},
pmid = {40450635},
issn = {2193-8229},
support = {2022R1A2C1010356//National Research Foundation of Korea/ ; RS-2023-00227939//National Research Foundation of Korea/ ; },
abstract = {INTRODUCTION: Following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, symptoms can persist for more than 12 weeks in over 10% of patients in a condition known as long coronavirus disease (COVID). Gut microbiota dysbiosis is correlated with long COVID, but the specific relationship between long COVID and the gut microbiome remains unclear. Here, we aimed to investigate connections between the gut microbiota and long COVID severity.

METHODS: Fecal samples were collected from 31 patients with long COVID, 14 with COVID-19 but not long COVID, and 23 healthy controls. The mean interval between COVID-19 diagnosis and sample collection was 65.5 (range: 13.0-110.3) weeks for patients with long COVID and 74.8 (range: 50.7-110.4) weeks for positive control group. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Patient-reported outcomes were used to comprehensively assess long COVID symptom severity.

RESULTS: Symptom severity was higher in patients with severe initial infections and significantly correlated with serum triglyceride, fasting blood glucose, and high-density lipoprotein-cholesterol levels. Results showed distinct microbial profiles in patients with long COVID. Leuconostoc, Actinomyces, and Granulicatella were significantly enriched, and they accurately distinguished patients with long COVID from controls, indicating their potential as long COVID biomarkers. Particular gut bacteria were significantly correlated with certain systemic, gastrointestinal, otolaryngologic, and visual symptoms. Parabacteroides, Eubacterium ventriosum group, and Rothia abundance was correlated with blood biomarkers that influence long COVID development, including total and low-density lipoprotein cholesterol and basophil levels.

CONCLUSIONS: The gut microbial signature of patients with long COVID differed from that of healthy controls. Certain microbial genera showed significant differences between patients with long COVID and controls, suggesting potential as preliminary biomarkers and therapeutic targets for long COVID pending validation in larger studies.},
}

@article {pmid40449327,
year = {2025},
author = {Robineau, O and Hüe, S and Surenaud, M and Lemogne, C and Dorival, C and Wiernik, E and Brami, S and Nicol, J and de Lamballerie, X and Blanché, H and Deleuze, JF and Ribet, C and Goldberg, M and Severi, G and Touvier, M and Zins, M and Levy, Y and Lelievre, JD and Carrat, F},
title = {Symptoms and pathophysiology of post-acute sequelae following COVID-19 (PASC): a cohort study.},
journal = {EBioMedicine},
volume = {117},
number = {},
pages = {105792},
doi = {10.1016/j.ebiom.2025.105792},
pmid = {40449327},
issn = {2352-3964},
abstract = {BACKGROUND: Several studies reported long-term consequences of severe COVID-19. However, pathophysiological mechanisms of Post-Acute Sequelae following COVID-19 (PASC) in patients with mild acute COVID-19 have been less investigated. Specifically, the link between PASC and immuno-inflammatory abnormalities is inconsistent in the literature. The hypothesis that different pathophysiological mechanisms could explain the persistent symptoms needs to be explored.

METHODS: The COPER cohort is a prospective study that included participants with PASC and with a history of COVID-19 without persistent symptoms. None were hospitalised for COVID-19. Participants underwent two home visits six months apart for biological sample collection and completed questionnaires on medical history, infection, vaccination, symptoms, and mental health. The study analysed association between persistent symptoms and 14 blood biomarkers, comparing participants with PASC with recovered participants.

FINDINGS: Between June and November 2022, 1000 participants were included in the study, 199 were excluded due to missing data or sample (35), SARS-CoV-2 infection less than 3 months (36) or lack of known SARS-CoV-2 infection and negative serology (128), with two groups analysed: recovered (n = 490), PASC (n = 311). Participants with PASC were more frequently women, had a higher BMI and a median number of 3 persistent symptoms, with common symptoms being asthenia, dyspnoea, cough, and sleep disorders. Biological analysis revealed significant associations between certain PACS symptoms and biomarkers of viral activation (IFNγ, IP-10), COVID-19 severity (CD163) and vascular activation (VCAM-1, ICAM-1), mainly in subjects whose symptoms had lasted less than a year. However, these associations did not persist over time.

INTERPRETATION: The results suggest a polymorphic and dynamic pathophysiology according to symptoms and time since infection. Other hypotheses, beyond those related to persistent inflammation, should be explored.

FUNDING: French Ministry of Health and Prevention and the French Ministry of Higher Education, Research and Innovation.},
}

@article {pmid40448188,
year = {2025},
author = {Mendenhall, E and Kamau, LW and Kenworthy, N and Bosire, EN},
title = {Digital activism in Kenya: moving from the digital center to the digital periphery of Long Covid experience.},
journal = {Globalization and health},
volume = {21},
number = {1},
pages = {33},
pmid = {40448188},
issn = {1744-8603},
abstract = {Digital activism around Long Covid has reverberated around the globe, as patients, researchers, and clinicians worked together to understand the chronic condition. However, Long Covid networks, much like other social networks, have hierarchies and barriers that can impede equitable access. In this article, we examine how the global digital center and periphery shape how people with Long Covid connect to networks to learn about their illness symptoms, diagnoses, treatments, and experiences. We introduce case narratives of two Kenyan women-one elite Nairobian who was connected to the digital center and another middle class woman who connected with her through a peripheral digital community-to describe how elite patients were engaged at the digital center, and non-elite patients were engaged in the periphery with digital and non-digital connections through which they cultivated other social networks to communicate, share, and experience their illness experiences. The Kenyan case study introduces a context where people have sophisticated digital lives and are engaged in global information networks. Yet, we argue that some Long Covid patients' experiences are impossible to divorce from the digital activism that has drawn together a remarkable global patient community, causing a ripple effect on how people define and experience the self and illness throughout the world. We conclude that many Kenyans may be engaging with digital networks differently and from different places of geographic, cultural, linguistic, and technological power, possibly cultivating divergent idioms, interpretations, and experiences of the post-viral condition. This demonstrates not only how social networks function at the digital periphery but also the complexities situated within the periphery itself, which is at important social nodes, connected to the digital center.},
}

@article {pmid40447142,
year = {2025},
author = {Vreeman, ECA and Pillay, J and Burgess, JK},
title = {Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {108891},
doi = {10.1016/j.pharmthera.2025.108891},
pmid = {40447142},
issn = {1879-016X},
abstract = {After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis. Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.},
}

@article {pmid40446594,
year = {2025},
author = {Koller, K and Herold, R and Morawa, E and Erim, Y},
title = {Coping competence and health outcomes in post-COVID: A prospective study on the role of adaptive strategies in symptom management and physical and mental health.},
journal = {Journal of psychosomatic research},
volume = {194},
number = {},
pages = {112152},
doi = {10.1016/j.jpsychores.2025.112152},
pmid = {40446594},
issn = {1879-1360},
abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC), characterized by persistent symptoms like fatigue, cognitive impairments, and mental health problems, requires effective coping strategies for symptom management, yet their impact on health outcomes in PASC patients remains unclear. This study examines differences in coping strategies across subgroups, changes over time, and their relationship with PASC symptoms and physical and mental health.

METHODS: In a prospective study, conducted at the Post-COVID Center of the University Hospital of Erlangen, patients were assessed at baseline (T0) and follow-up (T1; M = 4.46 months, SD = 2.27). Coping strategies were measured using the Patient Competence Questionnaire-2 (PCQ-2), including coping competence, religious/spiritual coping, healthy lifestyle, information-seeking, and adaptability. PASC symptom severity (PCS score), fatigue (FSS), post-exertional malaise (DSQ-PEM), and depressive symptoms (PHQ-9) were also assessed.

RESULTS: Among 339 participants (age: M = 45.51 years, SD = 11.96; 70.2 % women) coping competence improved significantly over time, while no notable changes were observed in the other factors and overall patient competence. Women scored higher than men in religious/spiritual coping, coping competence, and healthy lifestyle (all p < .001). Higher education levels were associated with higher scores in coping competence, information-seeking, and healthy lifestyle (p = .028, p = .014 and p = .012, respectively). Higher coping competence at T0 significantly predicted fewer symptoms of fatigue and depression (p = .021 and p < .001, respectively) at T1, whereas higher adaptability at T0 was associated with more severe fatigue, PEM, and depression at T1 (p < .001, p = .001 and p = .020, respectively).

CONCLUSION: Strengthening coping competence may improve symptom management and severity in PASC patients, highlighting the need for targeted interventions.

TRIAL REGISTRATION: DRKS00033621, https://drks.de/search/de/trial/DRKS00033621.},
}

@article {pmid40446093,
year = {2025},
author = {Niebauer, JH and Ahmet, I and Sarah, S and Christophe, C and Michael, K and Simon, S and John, F and Marc, S and Michael, L and Alexander, Z and Rosmarie, V and Sabine, H and Silvia, CR and Christian, K and Wolfgang, H and Christoph, W and Diana, B},
title = {Cardiopulmonary long-term effects 30 months after severe COVID-19 infection.},
journal = {European heart journal. Quality of care & clinical outcomes},
volume = {},
number = {},
pages = {},
doi = {10.1093/ehjqcco/qcaf035},
pmid = {40446093},
issn = {2058-1742},
abstract = {AIMS: The aim of this study was to assess symptoms and long-term cardiopulmonary impairments over a period of up to 30 months following severe COVID-19 infection.

METHODS: This prospective multicenter cohort study included 200 patients hospitalized between February 2020 and October 2021 with a PCR-confirmed COVID-19 infection. Follow-up examinations 6, 18 and 30 months post-discharge included electrocardiogram, transthoracic echocardiography, cardiac magnetic resonance imaging, chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test, and a laboratory panel.

RESULTS: 200 patients completed their 6-month follow-up after discharge and those with pathological findings on cardiopulmonary imaging received additional follow-ups at 18 and 30 months (170 and 139 patients, respectively).At 30 months, most of the cardiopulmonary imaging abnormalities had resolved. Only two patients with previously reduced left ventricular function had persistent mild impairment at 30 months [6 months: n=15 (8%)]. Pericardial effusion resolved in all patients but one [6 months: n=28 (17%)]. Signs of pericarditis and myocarditis had already regressed at the 18-month follow-up [6 months: n=7 (5%)].Chest CT scans showed partial improvement: only one patient had complete resolution at 30 months, while the remaining patients [30 months: n=17 (94%)] developed minor fibrotic and scarred tissue [6 months: n=41 (24%)].Long COVID incidence was high with 73% at 6 months and still 49% at 30 months, with no clear predictors identified.

CONCLUSION: Even though cardiopulmonary functional and structural abnormalities regressed over time, almost half of the patients still suffered from Long COVID at 30 months. The disconnect between pathological cardiopulmonary findings and reported symptoms, continues to pose a persistent clinical challenge in the understanding and managing Long COVID.},
}

@article {pmid40444408,
year = {2025},
author = {Wang, E and Patel, ZM},
title = {Paxlovid Is Associated With Lower Rates of Long COVID-19 Smell and Taste Disorders.},
journal = {International forum of allergy & rhinology},
volume = {},
number = {},
pages = {e23612},
doi = {10.1002/alr.23612},
pmid = {40444408},
issn = {2042-6984},
abstract = {BACKGROUND: Research is needed on treatments that prevent progression to long COVID-19 olfactory and gustatory dysfunction, which millions continue to suffer from. We sought to explore the utility of Paxlovid in decreasing rates of long COVID-19 smell and taste loss.

DESIGN: This case-control study at a single tertiary medical center examined patients who were acutely infected with COVID-19 and received Paxlovid from December 2021 to September 2023 and age-matched infected patients who did not receive Paxlovid. Occurrence of nasal congestion, rhinorrhea, facial pain/pressure and smell/taste loss were recorded both in the acute (<30 days for nasal congestion, rhinorrhea, facial pain/pressure; <90 days for smell/taste loss) and the long-term settings for both groups. Chi-square and t-tests were used to compare the two groups.

RESULTS: A total of 846 individuals had complete data (Paxlovid: 423, non-Paxlovid: 423). Significantly more individuals in the Paxlovid group experienced nasal congestion (p < 0.001) and rhinorrhea (p = 0.006) in the acute setting. However, resolution of these symptoms after 30 days did not differ between the Paxlovid and non-Paxlovid groups (p = 0.375 and p = 0.316, respectively). Facial pressure did not differ between the two groups in either the acute or long-term setting (p = 0.077 and p = 0.315). In the acute setting, there was no significant difference between groups in the number of patients experiencing olfactory/gustatory changes (p = 0.487). After taking Paxlovid however, individuals were less likely to experience long-term olfactory/gustatory changes (p < 0.001).

CONCLUSIONS: Early intervention with Paxlovid may decrease the risk of long COVID-19 smell/taste changes. Further study with a randomized controlled trial would help providers know more definitively if they should consider this utility in preventing long-term smell and taste loss.},
}

@article {pmid40444353,
year = {2025},
author = {Kisiangani, I and Jornada Ben, Â and Wynberg, E and Wami, W and Iddi, S and Kinya, I and Vassall, A and Kyobutungi, C and Ziraba, A and Njeru, J and Mugenda, O and Kiguoya, MW and Kimondo, M and Githua, G and de Jong, MD and Mohamed, SF and Asiki, G and Schultsz, C},
title = {Recovery and long-term health outcomes of SARS-CoV-2 infection in a prospective cohort in an urban setting, Kenya.},
journal = {Global health action},
volume = {18},
number = {1},
pages = {2500795},
doi = {10.1080/16549716.2025.2500795},
pmid = {40444353},
issn = {1654-9880},
mesh = {Humans ; Kenya/epidemiology ; *COVID-19/epidemiology/physiopathology ; Female ; Adult ; Male ; Prospective Studies ; Middle Aged ; Severity of Illness Index ; Young Adult ; SARS-CoV-2 ; Urban Population/statistics & numerical data ; Adolescent ; Time Factors ; },
abstract = {BACKGROUND: Evidence on long COVID remains limited in sub-Saharan countries.

OBJECTIVE: This study explored the occurrence of COVID-19-related symptoms and factors affecting recovery and long COVID severity in Nairobi, Kenya.

METHODS: A prospective cohort of individuals testing positive for SARS-CoV-2 between February 2022 and February 2023 was followed until June 2023. COVID-19-related symptoms were assessed every three months. Time to recovery was analyzed using survival analysis, while factors affecting recovery factors and long COVID severity using Cox proportional hazard and Poisson regression, respectively.

RESULTS: Among 291 participants (median age 34, 59.1% female), 42 (14%) had severe/critical infection. At 6 and 12 months post-positive PCR, 53.1% and 33.5% had ≥ 1 COVID-19-related symptoms, respectively. Fatigue (40.2%), pain (36.8%), sore throat (36.8%), headaches (36.4%), and loss of strength (31.6%) were most common. Median time to recovery was longer for severe/critical cases than mild/moderate (234 vs 206 days, p = 0.016). Participants aged 40-64 years experienced slower recovery than those aged < 40 years (aHR = 0.635 [95%CI, 0.429;0.941]). Participants with tertiary education recovered faster than those with primary education (aHR = 1.869 [95%CI, 1.050;3.327]). Long COVID severity was associated with female sex (aIRR = 1.418 [95%CI; 1.078;1.864]), tertiary education (aIRR, 0.489 [95%CI, 0.415;0.576]), and ≥ 1 comorbidity (aIRR = 2.415 [95%CI, 1.639;3.559]).

CONCLUSIONS: Six months post-infection, half had lingering symptoms, with a third still affected after a year. Recovery was faster in younger, educated individuals, while severe long COVID was more common in women, those with low education and pre-existing conditions. The burden of long COVID in Kenya requires support for vulnerable groups.},
}

Humans
Kenya/epidemiology
*COVID-19/epidemiology/physiopathology
Female
Adult
Male
Prospective Studies
Middle Aged
Severity of Illness Index
Young Adult
SARS-CoV-2
Urban Population/statistics & numerical data
Adolescent
Time Factors

@article {pmid40443486,
year = {2025},
author = {Islam, MW and Rahman, E and Hossain, KMA and Hossain, MZ},
title = {Scope of rehabilitation for patients with long COVID symptoms in Bangladesh.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1572351},
pmid = {40443486},
issn = {2673-6861},
abstract = {BACKGROUND: The Bangladeshi healthcare system had planned to meet the long-term rehabilitation needs of people who had suffered due to COVID, as well as those whose health and level of activity had declined during the COVID pandemic. The goal is to apply the COVID-19 Yorkshire Rehabilitation Scale (C-YRS) to ascertain the number of health domains in which a person with PCS should undergo rehabilitation.

METHODS: We carried out a quantitative cross-sectional study. The eight administrative divisions provided the pool of participants for selecting the 409 people comprised by the stratified sampling. We collected data using a semi-structured questionnaire that included sociodemographics, a symptoms checklist, and the C-YRS.

RESULTS: The most common post-COVID symptoms among the participants were fatigue (34.3%), muscle pain (20%), and dyspnea (12.2%). The comparison between pre- and postinfection symptoms revealed a notable increase in symptom severity and functional impairments. The study also found a significant relationship between symptom severity and place of residence (p < 0.5). The study found that the severity of symptoms was mild (30.5% (n = 90), moderate 55.3% (n = 186), and severe 14.2% (n = 94). We also looked for correlations between symptom severity, functional impairment, and health. It showed a significant positive correlation between symptom scores and functional difficulty scores (0.889, p < 0.001), while there was a significant negative correlation between symptom scores and overall health (-0.658, p < 0.001).

CONCLUSION: Severity phenotypes can aid in the stratification of people with PCS for targeted therapies and rehabilitation care planning.},
}

@article {pmid40374074,
year = {2025},
author = {Canziani, LM and Monforte, AD and Giannella, M and Rodríguez-Baño, J and Tacconelli, E},
title = {Bridging the evidence gap: expert consensus on management of SARS-CoV-2 acute infection and post-COVID-19 condition in immunocompromised patients.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.05.008},
pmid = {40374074},
issn = {1469-0691},
}

@article {pmid40441540,
year = {2025},
author = {Posharina, T and Varonen, M and Jarva, H and Kanerva, M and Liira, H and Laakso, SM},
title = {Serum antineuronal antibodies in patients with post-COVID-19 condition - association to intensive care.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbi.2025.05.026},
pmid = {40441540},
issn = {1090-2139},
abstract = {Post-COVID-19 condition (PCC), characterized by persistent symptoms following SARS-CoV-2 infection, is a global health challenge. Neurological symptoms are common in PCC, and immune-mediated mechanisms have been proposed as potential contributors. We set out to systematically explore serum antineuronal antibodies in patients with PCC and clinical factors associated with seropositivity. Our prospective, single-center cohort study included adult patients with a confirmed SARS-CoV-2 infection at least three months prior and a diagnosis of PCC. Serum and cerebrospinal fluid (CSF) samples were analyzed for the presence of antineuronal antibodies. A control group with confirmed SARS-CoV-2 infection but without PCC symptoms was included, age-, sex- and time from acute infection to sampling -matched to seropositive cases of PCC. Among 314 consecutive patients with PCC, 38 (12.1 %) tested positive for serum antineuronal antibodies. CSF analysis was performed for a subset; however, no intrathecal autoantibodies were detected. The most prevalent serum autoantibodies targeted CASPR-2 (n = 7, 18.9 %), neurofascin-186 (n = 5, 13.2 %), and glycine receptor (n = 4, 10.8 %). Multinomial logistic regression identified intensive care unit (ICU) admission during acute COVID-19 as the only significant predictor of autoantibody positivity (OR 3.4; 95 % CI: 1.0-10.4). Of the 35 control subjects, two (5.7 %) tested seropositive: one with low titer myelin oligodendrocyte glycoprotein antibodies and another with borderline myelin antibody levels. None of the patients met criteria for autoimmune encephalitis, and neurological assessments and brain magnetic resonance imaging were unremarkable. Neuropsychological testing showed a trend toward impairments in attention and executive functions among seropositive individuals. Thus, there was no significant difference in the prevalence of serum antineuronal antibodies in PCC compared to post-infection controls, and the association between seropositivity and ICU admission suggested systemic immune activation rather than a specific autoantibody-mediated mechanism. It remains unclear whether observed neuropsychological deficits are attributable to autoantibodies or the effects of critical illness.},
}

@article {pmid40439483,
year = {2025},
author = {Krishnan, JA and Cao, B and Chotirmall, SH and Ely, EW and Openshaw, P and Roche, N and Waterer, G},
title = {Using the 2024 NASEM Definition of Long COVID: Implications for Pulmonary and Critical Care Medicine.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
pmid = {40439483},
issn = {1535-4970},
}

@article {pmid40438846,
year = {2025},
author = {Idris Fadul, AA and Osman Mohamed, AA and Mohammed Ahmed, AAS and Elmobark, S and Merghani Hammour, AS and Elgaleel Khir Elsiad, NMN and Mohammed Elhaj, EA},
title = {Post-coronavirus Disease 2019 (COVID-19) Cardiovascular Manifestations: A Systematic Review of Long-Term Risks and Outcomes.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83083},
pmid = {40438846},
issn = {2168-8184},
abstract = {Emerging evidence suggests that coronavirus disease 2019 (COVID-19) survivors face increased risks of cardiovascular complications, but the long-term risks, underlying mechanisms, and clinical implications remain incompletely characterized. This systematic review synthesizes current evidence on post-COVID-19 cardiovascular manifestations, evaluating their incidence, pathophysiology, and outcomes. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Fifteen observational studies (cohort, case-control, cross-sectional) meeting predefined eligibility criteria, confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, cardiovascular outcomes assessed ≥4 weeks post-infection, sample sizes >10, and peer-reviewed publication, were included. The risk of bias was assessed using the Newcastle-Ottawa Scale. The multinational studies (United States, Europe, Asia, South America) involved diverse populations (n=80-8,126,462), with follow-up durations ranging from three to 24 months. Mechanisms such as endothelial dysfunction, myocardial inflammation, and autonomic dysregulation were consistently supported across studies via imaging (e.g., cardiac MRI) and biomarkers (e.g., troponin, C-reactive protein (CRP)). Persistent arrhythmias and subclinical myocardial injury were directly demonstrated in 40-60% of patients. Worse outcomes were associated with hospitalization during acute infection, preexisting cardiovascular disease, and metabolic syndrome. Heterogeneity in follow-up durations may limit the detection of very-late-onset complications, though risks remained elevated across all intervals. Individualized management strategies should include cardiovascular imaging (echocardiography, MRI), biomarker profiling, and tailored pharmacotherapy (anti-inflammatory agents, anticoagulants). The ethical rationale for randomized trials is now strengthened by the clear evidence of long-term risks; ongoing trials are testing targeted anti-inflammatory and anticoagulant regimens. These findings underscore the necessity of systematic cardiovascular surveillance and risk-stratified care for COVID-19 survivors. Future research should prioritize extended follow-up studies and randomized controlled trials (RCTs) to optimize interventions for this growing population.},
}

@article {pmid40436612,
year = {2025},
author = {Daynes, E and Barker, RE and Jones, AV and Walsh, JA and Nolan, CM and Man, WD and Singh, SJ and Greening, NJ and Houchen-Wolloff, L and Evans, RA},
title = {Determining the minimum important differences for field walking tests in adults with long-term conditions: a systematic review and meta-analysis.},
journal = {European respiratory review : an official journal of the European Respiratory Society},
volume = {34},
number = {176},
pages = {},
doi = {10.1183/16000617.0198-2024},
pmid = {40436612},
issn = {1600-0617},
mesh = {Humans ; *Walk Test ; *Exercise Tolerance ; Time Factors ; Predictive Value of Tests ; Male ; Female ; *Minimal Clinically Important Difference ; Reproducibility of Results ; Adult ; Middle Aged ; *Lung/physiopathology ; *Walking ; Aged ; *Respiratory Tract Diseases/diagnosis/physiopathology/therapy ; *Heart Diseases/diagnosis/physiopathology ; Prognosis ; *Exercise Test ; *Nervous System Diseases/diagnosis/physiopathology ; Chronic Disease ; },
abstract = {IMPORTANCE: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions.

METHODS: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan.

RESULTS: 42 studies were included in the analyses, involving n=13 949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25 m (24-26 m) for respiratory conditions, 23 m (8-37 m) for cardiac conditions and 37 m (26-49 m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48 m (39-57 m) for respiratory conditions and 70 m (55-85 m) for cardiac conditions. The MID for ESWT in COPD was 159 s (94-224 s). The pooled MID across conditions within exercise interventions was 26 m (22-40 m) for the 6MWD and 53 m (44-62 m) for the ISWT, with reasonable heterogeneity (I[2]=48% and I[2]=47%, respectively).

CONCLUSION: We propose new MIDs for exercise interventions using anchor-based methodology in long‑term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta‑analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking.},
}

Humans
*Walk Test
*Exercise Tolerance
Time Factors
Predictive Value of Tests
Male
Female
*Minimal Clinically Important Difference
Reproducibility of Results
Adult
Middle Aged
*Lung/physiopathology
*Walking
Aged
*Respiratory Tract Diseases/diagnosis/physiopathology/therapy
*Heart Diseases/diagnosis/physiopathology
Prognosis
*Exercise Test
*Nervous System Diseases/diagnosis/physiopathology
Chronic Disease

@article {pmid40435383,
year = {2025},
author = {Nairn, B and Tsakanikas, V and Gordon, B and Karapintzou, E and Kaski, D and Fotiadis, DI and Bamiou, DE},
title = {Smart Wearable Technologies for Balance Rehabilitation in Older Adults at Risk of Falls: Scoping Review and Comparative Analysis.},
journal = {JMIR rehabilitation and assistive technologies},
volume = {12},
number = {},
pages = {e69589},
doi = {10.2196/69589},
pmid = {40435383},
issn = {2369-2529},
abstract = {BACKGROUND: Falls among older adults are a significant public health concern, often leading to severe injuries, decreased quality of life, and substantial health care costs. Smart wearable technologies for balance rehabilitation present a promising avenue for addressing the falls epidemic, capable of providing detailed objective movement data, engaging visuals, and real-time feedback. With the recent and rapid evolution of innovative technologies, including artificial intelligence (AI), augmented reality (AR) or virtual reality (VR), and motion tracking, there is a need to evaluate the market to identify the most effective and accessible smart balance systems currently available.

OBJECTIVE: This study aims to evaluate the current landscape of smart wearable technology systems for balance rehabilitation in older adults at risk of falls. In addition, it aims to compare market-available systems to the telerehabilitation of balance clinical and economic decision support system (TeleRehab DSS), a recently developed smart balance system.

METHODS: A scoping review and strengths, weaknesses, opportunities, and threats (SWOT) analysis was completed, exploring the landscape of smart balance systems in older adults at risk of falls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, electronic databases PubMed, MEDLINE, and Cochrane were systematically searched for articles in English from July 1, 2014, to July 1, 2024. Gray literature searches of relevant institutions and web pages were also conducted. The database search and commercial systems were then compared against the TeleRehab DSS in a SWOT analysis.

RESULTS: The scoping review yielded 17 systems that met the inclusion criteria; 10 investigational systems and 7 commercially available systems. Out of 10 studies, only 1 reported the use of intelligent learning or AI, 8 studies reported the use of motion tracking, and 9 studies used virtual reality. Of the studies incorporating motion tracking, 3 provided feedback as either visual or auditory. All but 2 studies reported the use of gamification, and 7 studies incorporated balance exercises. In total, 2 studies reported remote delivery, with 5 being clinician-supervised and 4 providing a clinician report. The SWOT analysis of TeleRehab DSS against the 7 market-available smart balance systems revealed several unique advantages, including personalized therapy with AI-DSS, AR for real-world interaction, enhanced clinician involvement, and comprehensive data analytics.

CONCLUSIONS: The findings from this scoping review highlight the rapid evolution of smart balance systems, yet significant gaps remain in AI integration, remote accessibility, and clinician-driven data analytics. Despite limitations such as cost, accessibility, and user training requirements, TeleRehab DSS emerges as a significant innovation, addressing many of these gaps through AI-driven personalization, AR for real-world interaction, and real-time clinician monitoring. These features position it as a next-generation solution that aligns closely with the evolving needs of patients and clinicians. The results of this review provide valuable insights for future research, supporting the need for further validation studies and the development of more intelligent and accessible balance rehabilitation technologies.},
}

@article {pmid40434132,
year = {2025},
author = {Metcalfe, J and Scoullar, MJL and Whyler, NCA and Balkin, H and Tippett, E},
title = {Beyond time as the healer: action in long COVID treatment to improve patient outcomes.},
journal = {Internal medicine journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/imj.70099},
pmid = {40434132},
issn = {1445-5994},
abstract = {Long COVID is complex and disabling. Despite emerging therapies, the lack of guidelines and clinician awareness delays treatment. This paper highlights options available now to improve function and quality of life. We call for a symptom-focused, person-centred approach that incorporates lived experience and clinical judgement to bridge the gap between evidence and care. Time alone is not the answer.},
}

@article {pmid40433308,
year = {2025},
author = {Chowdhury, SR and Islam, N and Zhou, Q and Hasan, MK and Chowdhury, MR and Siemieniuk, RA and Agarwal, A and Brignardello-Petersen, R and Agoritsas, T and Olav Vandvik, P and Zeraatkar, D and Guyatt, G},
title = {Metformin for covid-19: systematic review and meta-analysis of randomised controlled trials.},
journal = {BMJ medicine},
volume = {4},
number = {1},
pages = {e001126},
doi = {10.1136/bmjmed-2024-001126},
pmid = {40433308},
issn = {2754-0413},
abstract = {OBJECTIVE: To summarise the effects of metformin on covid-19 to inform a World Health Organization (WHO) clinical practice guideline.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: As part of a living systematic review and network meta-analysis of drug treatments for covid-19 (covid-19 LNMA), a search was performed of the WHO covid-19 database, six Chinese databases, and the Epistemonikos Foundation's Living Overview of the Evidence covid-19 Repository (covid-19 L-OVE).

Randomised controlled trials that compared metformin with placebo in patients with acute covid-19 infection.

DATA SYNTHESIS: Frequentist pairwise meta-analyses were performed using the restricted maximum likelihood random effects model. The effects of interventions on selected outcomes were summarised using risk ratios, risk difference, and mean difference when appropriate, along with their corresponding 95% confidence intervals (CIs). To estimate absolute effects, the control arm event rate was used as the baseline risk. The risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool and the certainty of evidence using the GRADE (grading of recommendations assessment, development and evaluation) approach, with the minimally important difference in effect as the threshold.

RESULTS: Three randomised controlled trials of 1869 patients were included; one study provided long term follow-up on long covid. Metformin might have little or no impact on mortality (risk ratio 0.76, 95% CI 0.30 to 1.90; risk difference 3 fewer per 1000, 95% CI 8 fewer to 11 more; low certainty). The effects of metformin on admission to hospital because of covid-19 remain uncertain (risk ratio 0.74, 95% CI 0.28 to 1.95; risk difference 15 fewer per 1000, 95% CI 42 fewer to 55 more; very low certainty). Metformin results in little or no difference in adverse effects leading to discontinuation (risk difference 0.2 more per 1000, 95% CI 2.7 fewer to 3.1 more; high certainty). Metformin might decrease the development of long covid (risk ratio 0.6, 95% CI 0.4 to 0.9; risk difference 41 fewer per 1000, 95% CI 62 fewer to 10 fewer; low certainty). However, the effect is based on a single trial of 1126 patients, which has a high risk of bias owing to missing data, and nearly half of the participants were unvaccinated.

CONCLUSIONS: Current evidence based on randomised trials suggests no significant effect of metformin on acute clinical outcomes in patients with non-severe covid-19. Metformin might reduce the incidence of long covid when used to treat patients with non-severe acute covid-19 infection, but this was suggested by low certainty evidence from a single trial.},
}

@article {pmid40431734,
year = {2025},
author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS},
title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/v17050724},
pmid = {40431734},
issn = {1999-4915},
support = {25-BR-02-03//Korea Brain Research Institute/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*COVID-19/complications/metabolism/virology/pathology
*SARS-CoV-2/physiology
*Neurodegenerative Diseases/metabolism/virology/pathology/etiology
Virus Replication
Animals

@article {pmid40431631,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/v17050619},
pmid = {40431631},
issn = {1999-4915},
mesh = {*Spike Glycoprotein, Coronavirus/metabolism/genetics ; Humans ; *COVID-19/virology/physiopathology/complications/metabolism ; *SARS-CoV-2/metabolism/genetics/physiology ; *Receptors, Virus/metabolism ; Protein Binding ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has had a significant impact on global health through both acute illness, referred to as coronavirus disease 2019 (COVID-19), and chronic conditions (long COVID or post-acute sequelae of COVID-19, PASC). Despite substantial advancements in preventing severe COVID-19 cases through vaccination, the rise in the prevalence of long COVID syndrome and a notable degree of genomic mutation, primarily in the S protein, underscores the necessity for a deeper understanding of the underlying pathophysiological mechanisms related to the S protein of SARS-CoV-2. In this review, the latest part of this series, we investigate the potential pathophysiological molecular mechanisms triggered by the interaction between the spike protein and cellular receptors. Therefore, this review aims to provide a differential and focused view on the mechanisms potentially activated by the binding of the spike protein to canonical and non-canonical receptors for SARS-CoV-2, together with their possible interactions and effects on the pathogenesis of long COVID.},
}

*Spike Glycoprotein, Coronavirus/metabolism/genetics
Humans
*COVID-19/virology/physiopathology/complications/metabolism
*SARS-CoV-2/metabolism/genetics/physiology
*Receptors, Virus/metabolism
Protein Binding
Post-Acute COVID-19 Syndrome

@article {pmid40431629,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Saldanha-Araujo, F and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 1: Impact of Spike Protein in Pathophysiological Mechanisms of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/v17050617},
pmid = {40431629},
issn = {1999-4915},
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/complications/virology/physiopathology/pathology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has resulted in more than 700 million cases and nearly 7 million deaths worldwide. Although vaccination efforts have effectively reduced mortality and transmission rates, a significant proportion of recovered patients-up to 40%-develop long COVID syndrome (LC) or post-acute sequelae of COVID-19 infection (PASC). LC is characterized by the persistence or emergence of new symptoms following initial SARS-CoV-2 infection, affecting the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Despite the broad range of clinical symptoms that have been described, the risk factors and pathogenic mechanisms behind LC remain unclear. This review, the first of a two-part series, is distinguished by the discussion of the role of the SARS-CoV-2 spike protein in the primary mechanisms underlying the pathophysiology of LC.},
}

Humans
*Spike Glycoprotein, Coronavirus/metabolism
*COVID-19/complications/virology/physiopathology/pathology
*SARS-CoV-2/pathogenicity
Post-Acute COVID-19 Syndrome

@article {pmid40431432,
year = {2025},
author = {Matsuda, Y and Sakurada, Y and Nakano, Y and Otsuka, Y and Tokumasu, K and Honda, H and Soejima, Y and Yokota, Y and Takase, R and Omura, D and Otsuka, F},
title = {Clinical Characteristics of Vitamin D Deficiency Detected in Long COVID Patients During the Omicron Phase.},
journal = {Nutrients},
volume = {17},
number = {10},
pages = {},
doi = {10.3390/nu17101692},
pmid = {40431432},
issn = {2072-6643},
support = {23fk0108585h0001//Japan Agency for Medical Research and Development/ ; },
mesh = {Humans ; Female ; *Vitamin D Deficiency/blood/complications/epidemiology/diagnosis ; Male ; *COVID-19/complications/blood/epidemiology ; Retrospective Studies ; Middle Aged ; Vitamin D/blood/analogs & derivatives ; SARS-CoV-2 ; Aged ; Adult ; },
abstract = {Background: To characterize the clinical significance of vitamin D deficiency (VDD) detected in long COVID, a retrospective observational study was performed for outpatients who visited our clinic during the period from May 2024 to November 2024. Methods: Clinical trends in long COVID patients diagnosed with VDD who showed serum concentrations of 25-hydroxyvitamin D (25-OHD) lower than 20 ng/mL were compared with those in long COVID patients in a non-deficient vitamin D (NDD) group. Results: Of 126 patients with long COVID, 97 patients (female: 50) who had been infected during the Omicron phase were included. Sixty-six patients (68%) were classified in the VDD group. The median serum concentrations of 25-OHD were 14.8 ng/mL in the VDD group and 22.9 ng/mL in the NDD group. There were no significant differences between the two groups in terms of age, gender, BMI, severity of COVID-19, period after infection and vaccination history. Although the levels of serum calcium and phosphate were not significantly different between the two groups, the percentages of patients in the VDD group who complained of dizziness, memory impairment, palpitation and appetite loss were larger than those in the NDD group. Of note, the patients who complained of palpitation showed significantly lower concentrations of serum 25-OHD than those in the patients without palpitation (median: 11.9 vs. 17.3 ng/mL). Moreover, patients in the VDD group had significantly higher scores for physical and mental fatigue as well as higher scores for depressive symptoms. Conclusions: Collectively, VDD is involved in clinical manifestations of long COVID, particularly symptoms of palpitation, fatigue and depression.},
}

Humans
Female
*Vitamin D Deficiency/blood/complications/epidemiology/diagnosis
Male
*COVID-19/complications/blood/epidemiology
Retrospective Studies
Middle Aged
Vitamin D/blood/analogs & derivatives
SARS-CoV-2
Aged
Adult

@article {pmid40430532,
year = {2025},
author = {Kell, DB and Pretorius, E and Zhao, H},
title = {A Direct Relationship Between 'Blood Stasis' and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {5},
pages = {},
doi = {10.3390/ph18050712},
pmid = {40430532},
issn = {1424-8247},
abstract = {'Blood stasis' (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (). Similar concepts exist in Traditional Korean Medicine ('Eohyul') and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down ('stasis') of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke.},
}

@article {pmid40430247,
year = {2025},
author = {Takács, J and Deák, D and Seregély, B and Koller, A},
title = {Cognitive Slowing, Dysfunction in Verbal Working Memory, Divided Attention and Response Inhibition in Post COVID-19 Condition in Young Adults.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/life15050821},
pmid = {40430247},
issn = {2075-1729},
support = {TKP2020-NKA-17//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; TKP2021-EGA-37//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; OTKA K 132596//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; TKP2021-EGA-25//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; EKÖP-2024-151//MINISTRY FOR INNOVATION AND TECHNOLOGY HUNGARY, NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; Post-Covid 2021-34//HUNGARIAN ACADEMY OF SCIENCES/ ; ÚNKP-22-4-II-SE-4//NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR INNOVATION AND TECHNOLOGY FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND/ ; },
abstract = {After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive function. A total of 107 young adults, university students aged 18-34 years, participated. In total, 68.2% had contracted SARS-CoV-2; 21.9% showed PCC. Three groups were compared: no-C19 (COVID-19-negative controls), C19 (COVID-19-recovered without PCC) and PCC. Attention and executive function were measured with the Vienna Test System (Schuhfried[®], Mödling, Austria). In verbal working memory, the PCC group had a significantly lower performance with a moderate effect. The rate of below-average performance was higher in PCC (56.2%) compared to no-C19 (20.6%) and C19 (15.8%). In divided attention and response inhibition, PCC also showed lower performance, 62.5% and 37.5%, respectively, than no-C19 and C19. The co-occurrence of decreased cognitive functions was pronounced in PCC. The present study revealed significant long-lasting cognitive dysfunction in PCC in young adults, two years after COVID-19 infection. Verbal working memory was significantly impaired, and a lower performance was found in divided attention and response inhibition. In addition, there was an increased reaction time in most cognitive tasks, demonstrating cognitive slowing in young people with PCC.},
}

@article {pmid40430160,
year = {2025},
author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I},
title = {Vitamin D and COVID-19: Clinical Evidence and Immunological Insights.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/life15050733},
pmid = {40430160},
issn = {2075-1729},
abstract = {Vitamin D has emerged as a potential modulator of immune responses, sparking interest in its role in COVID-19 susceptibility and clinical outcomes. This review synthesizes current clinical evidence and explores immunological insights into the relationship between vitamin D levels and COVID-19 infection severity. Epidemiological studies indicate an inverse correlation between vitamin D deficiency and an increased risk of severe disease, hospitalization, and mortality in COVID-19 patients. Immunologically, vitamin D exerts regulatory effects on both innate and adaptive immunity, enhancing antimicrobial defense mechanisms, reducing excessive inflammatory responses, and potentially mitigating cytokine storm events observed in severe COVID-19 cases. Despite promising observational data, clinical trials evaluating vitamin D supplementation have shown mixed results, underscoring the need for standardized dosing regimens and patient stratification. Future research should focus on large-scale randomized controlled trials to conclusively determine the therapeutic potential and optimal supplementation strategies for vitamin D in managing COVID-19.},
}

@article {pmid40430026,
year = {2025},
author = {Martín-Martínez, E and Gil-Perotin, S and Giménez-Orenga, K and Barea-Moya, L and Oltra, E},
title = {HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104885},
pmid = {40430026},
issn = {1422-0067},
support = {CIAICO 2021/103//Generalitat Valenciana/ ; ACIF2021/179//Generalitat Valenciana/ ; },
mesh = {Humans ; *Rituximab/therapeutic use ; Male ; *Endogenous Retroviruses/genetics ; *Multiple Sclerosis/drug therapy/virology ; Adult ; *Fatigue Syndrome, Chronic/drug therapy/virology ; COVID-19 ; },
abstract = {This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments. Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient's blood supportive of an altered immune system. Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.},
}

Humans
*Rituximab/therapeutic use
Male
*Endogenous Retroviruses/genetics
*Multiple Sclerosis/drug therapy/virology
Adult
*Fatigue Syndrome, Chronic/drug therapy/virology
COVID-19

@article {pmid40429947,
year = {2025},
author = {Madè, A and Piella, SN and Ranucci, M and Gaetano, C and Renna, LV and Cardani, R and Spinetti, G and Milani, V and Martelli, F},
title = {LEF1-AS1 Deregulation in the Peripheral Blood of Patients with Persistent Post-COVID Symptoms.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104806},
pmid = {40429947},
issn = {1422-0067},
support = {Ricerca Corrente 2024 1.07.128//Ministero della Salute/ ; RF-2019-12368521//Ministero della Salute/ ; POS-T4 CAL.HUB.RIA T4-AN-09//Ministero della Salute/ ; Monica Stupino fund//FMM/ ; PNRRMAD-2022-12375790//Next Generation EU-NRRP M6C2 Inv. 2.1/ ; EU PNRR/2022/C9/MCID/I8//Next Generation EU-NRRP M6C2 Inv. 2.1/ ; Ricerca Corrente and 5Xmille to the IRCCS MultiMedica 2024//Ministero della Salute/ ; },
mesh = {Humans ; *COVID-19/blood/genetics ; Male ; Middle Aged ; *RNA, Long Noncoding/blood/genetics ; Case-Control Studies ; Female ; MicroRNAs/genetics/blood ; SARS-CoV-2 ; Biomarkers/blood ; *Lymphoid Enhancer-Binding Factor 1/genetics/blood ; Aged ; Leukocytes, Mononuclear/metabolism ; Adult ; },
abstract = {Long COVID denotes the persistence of symptoms after acute SARS-CoV-2 infection lasting for at least two months without another identifiable cause. Affecting an estimated 15% of COVID-19 patients, long COVID manifests in a wide range of symptoms. Despite extensive research on its one-year effects, limited data exist beyond 12 months. Due to the different manifestations of long COVID, its diagnosis can be challenging. Identifying potential mechanistic contributors and biomarkers would be highly valuable. Recent studies have highlighted the potential of noncoding RNAs (ncRNAs) as biomarkers for disease stratification in COVID-19. Specifically, we have recently identified miR-144-3p and a subset of lncRNAs as candidates for assessing disease severity and outcomes in COVID-19. This nested case-control study extends such investigations to 98 long COVID patients recruited 18 months after hospitalization, exploring the relationship between circulating ncRNA expression and persistent symptoms. While miR-144-3p, HCG18, and lncCEACAM21 expression did not differ between symptomatic and asymptomatic patients, LEF1-AS1 was downregulated in the peripheral blood mononuclear cells (PBMCs) of symptomatic patients. Of note, multiple LEF1-AS1 isoforms and LEF1 sense transcript levels were reduced and negatively correlated with relevant clinical markers. While further studies are needed, our discoveries offer new perspectives on the diagnosis and management of persistent long COVID.},
}

Humans
*COVID-19/blood/genetics
Male
Middle Aged
*RNA, Long Noncoding/blood/genetics
Case-Control Studies
Female
MicroRNAs/genetics/blood
SARS-CoV-2
Biomarkers/blood
*Lymphoid Enhancer-Binding Factor 1/genetics/blood
Aged
Leukocytes, Mononuclear/metabolism
Adult

@article {pmid40429836,
year = {2025},
author = {Fernandez, JA and Han, Q and Rajczewski, AT and Kono, T and Weirath, NA and Lee, AS and Rahim, A and Tretyakova, NY},
title = {Multi-Omics Analysis of the Epigenetic Effects of Inflammation in Murine Type II Pneumocytes.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104692},
pmid = {40429836},
issn = {1422-0067},
support = {CA095039 and CA248019/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Lipopolysaccharides ; *Epigenesis, Genetic ; DNA Methylation ; *Alveolar Epithelial Cells/metabolism/pathology/drug effects ; *Inflammation/genetics/metabolism/pathology/chemically induced ; Lung Neoplasms/genetics/pathology/metabolism ; Multiomics ; },
abstract = {Chronic inflammation plays a central role in the pathogenesis of lung diseases including asthma, long COVID, chronic obstructive pulmonary disease (COPD), and lung cancer. Lipopolysaccharide (LPS) is a potent inflammatory agent produced by Gram-negative bacteria and also found in cigarette smoke. Our earlier study revealed that the intranasal exposure of A/J mice to LPS for 7 days altered gene expression levels in alveolar Type II epithelial cells (AECIIs), which serve as precursors to lung adenocarcinoma and are also preferentially targeted by SARS-CoV-2. In the present work, we employed a comprehensive multi-omics approach to characterize changes in DNA methylation/hydroxymethylation, gene expression, and global protein abundances in the AECIIs of A/J mice following the sub-chronic exposure to LPS and after a 4-week recovery period. Exposure to LPS led to hypermethylation at regulatory elements within the genome such as enhancer regions and expression changes in genes known to play a role in lung cancer tumorigenesis. Changes in protein abundance were consistent with an inflammatory phenotype and also included tumor suppressor proteins. Integration of the multi-omics data resulted in a model where LPS-driven inflammation in AECIIs triggers epigenetic changes that, along with genetic mutations, may contribute to lung cancer development.},
}

Animals
Mice
Lipopolysaccharides
*Epigenesis, Genetic
DNA Methylation
*Alveolar Epithelial Cells/metabolism/pathology/drug effects
*Inflammation/genetics/metabolism/pathology/chemically induced
Lung Neoplasms/genetics/pathology/metabolism
Multiomics

@article {pmid40429727,
year = {2025},
author = {Ignacio-Mejía, I and Bandala, C and González-Zamora, JF and Chavez-Galan, L and Buendia-Roldan, I and Pérez-Torres, K and Rodríguez-Díaz, MZ and Pacheco-Tobón, DX and Quintero-Fabián, S and Vargas-Hernández, MA and Carrasco-Vargas, H and Falfán-Valencia, R and Pérez-Rubio, G and Hernández-Lara, KA and Gómez-Manzo, S and Ortega-Cuellar, D and Ignacio-Mejía, F and Cárdenas-Rodríguez, N},
title = {Association of Vitamin D Supplementation with Glutathione Peroxidase (GPx) Activity, Interleukine-6 (IL-6) Levels, and Anxiety and Depression Scores in Patients with Post-COVID-19 Condition.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104582},
pmid = {40429727},
issn = {1422-0067},
support = {2022/C-015//Instituto Nacional de Pediatria/ ; C32-22//Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas/ ; },
mesh = {Humans ; *Glutathione Peroxidase/blood/metabolism ; *Interleukin-6/blood ; Male ; Female ; *Anxiety/drug therapy/etiology/blood ; *Depression/etiology/drug therapy/blood ; *Dietary Supplements ; *COVID-19/complications/psychology/blood ; Middle Aged ; *Vitamin D/administration & dosage ; Adult ; SARS-CoV-2 ; Aged ; },
abstract = {Coronavirus disease 2019 (COVID-19) presents with various symptoms, and some patients develop post-COVID-19 condition (PCC). Vitamin D has shown therapeutic potential in COVID-19 and may offer benefits for PCC. The aim of this study was to evaluate the differences associated with two supplementation strategies (bolus and daily) on interleukin-6 (IL-6) levels, glutathione peroxidase (GPx) activity, and clinical outcomes in PCC patients, regardless of whether target 25 (OH) D levels reached the ideal range. We conducted a self-controlled study in which 54 participants with PCC were supplemented with vitamin D3 (n = 28 bolus and n = 26 daily) for 2 months. Blood samples were collected to measure IL-6 levels and GPx activity using spectrophotometric methods. The Hospital Anxiety and Depression Scale (HADS) was used to assess mental function. Both bolus and daily vitamin D supplementation were significantly associated with increased GPx activity and decreased IL-6 levels. Daily supplementation was additionally associated with a significant reduction in anxiety and depression scores. However, neither regimen was associated with improvements in cough, dyspnea, or fatigue. These findings suggest a potential association between vitamin D supplementation and improvements in antioxidant and neuropsychiatric parameters in PCC, possibly mediated by its immunomodulatory and antioxidant properties. Further placebo-controlled trials are warranted to determine whether these observed associations reflect causal relationships.},
}

Humans
*Glutathione Peroxidase/blood/metabolism
*Interleukin-6/blood
Male
Female
*Anxiety/drug therapy/etiology/blood
*Depression/etiology/drug therapy/blood
*Dietary Supplements
*COVID-19/complications/psychology/blood
Middle Aged
*Vitamin D/administration & dosage
Adult
SARS-CoV-2
Aged

@article {pmid40429707,
year = {2025},
author = {Semo, D and Shomanova, Z and Sindermann, J and Mohr, M and Evers, G and Motloch, LJ and Reinecke, H and Godfrey, R and Pistulli, R},
title = {Persistent Monocytic Bioenergetic Impairment and Mitochondrial DNA Damage in PASC Patients with Cardiovascular Complications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104562},
pmid = {40429707},
issn = {1422-0067},
support = {SEED/018/23//IZKF SEED/ ; GO121222//Innovative Medizinische Forschung/ ; },
mesh = {Humans ; *Monocytes/metabolism/pathology ; *DNA, Mitochondrial/genetics/metabolism ; *COVID-19/complications/metabolism/pathology ; Male ; Female ; Middle Aged ; *DNA Damage ; Oxidative Stress ; *Cardiovascular Diseases/metabolism/etiology/pathology ; SARS-CoV-2 ; Membrane Potential, Mitochondrial ; Reactive Oxygen Species/metabolism ; Aged ; Mitochondria/metabolism ; *Energy Metabolism ; Lipopolysaccharide Receptors/metabolism ; Case-Control Studies ; },
abstract = {Cardiovascular complications are a hallmark of Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC), yet the mechanisms driving persistent cardiac dysfunction remain poorly understood. Emerging evidence implicates mitochondrial dysfunction in immune cells as a key contributor. This study investigated whether CD14[++] monocytes from long COVID patients exhibit bioenergetic impairment, mitochondrial DNA (mtDNA) damage, and defective oxidative stress adaptation, which may underlie cardiovascular symptoms in PASC. CD14[++] monocytes were isolated from 14 long COVID patients with cardiovascular symptoms (e.g., dyspnea, angina) and 10 age-matched controls with similar cardiovascular risk profiles. Mitochondrial function was assessed using a Seahorse Agilent Analyzer under basal conditions and after oxidative stress induction with buthionine sulfoximine (BSO). Mitochondrial membrane potential was measured via Tetramethylrhodamine Ethyl Ester (TMRE) assay, mtDNA integrity via qPCR, and reactive oxygen species (ROS) dynamics via Fluorescence-Activated Cell Sorting (FACS). Parallel experiments exposed healthy monocytes to SARS-CoV-2 spike protein to evaluate direct viral effects. CD14[++] monocytes from long COVID patients with cardiovascular symptoms (n = 14) exhibited profound mitochondrial dysfunction compared to age-matched controls (n = 10). Under oxidative stress induced by buthionine sulfoximine (BSO), long COVID monocytes failed to upregulate basal respiration (9.5 vs. 30.4 pmol/min in controls, p = 0.0043), showed a 65% reduction in maximal respiration (p = 0.4035, ns) and demonstrated a 70% loss of spare respiratory capacity (p = 0.4143, ns) with significantly impaired adaptation to BSO challenge (long COVID + BSO: 9.9 vs. control + BSO: 54 pmol/min, p = 0.0091). Proton leak, a protective mechanism against ROS overproduction, was blunted in long COVID monocytes (3-fold vs. 13-fold elevation in controls, p = 0.0294). Paradoxically, long COVID monocytes showed reduced ROS accumulation after BSO treatment (6% decrease vs. 1.2-fold increase in controls, p = 0.0015) and elevated mitochondrial membrane potential (157 vs. 113.7 TMRE fluorescence, p = 0.0179), which remained stable under oxidative stress. mtDNA analysis revealed severe depletion (80% reduction, p < 0.001) and region-specific damage, with 75% and 70% reductions in amplification efficiency for regions C and D (p < 0.05), respectively. In contrast, exposure of healthy monocytes to SARS-CoV-2 spike protein did not recapitulate these defects, with preserved basal respiration, ATP production, and spare respiratory capacity, though coupling efficiency under oxidative stress was reduced (p < 0.05). These findings suggest that mitochondrial dysfunction in long COVID syndrome arises from maladaptive host responses rather than direct viral toxicity, characterized by bioenergetic failure, impaired stress adaptation, and mitochondrial genomic instability. This study identifies persistent mitochondrial dysfunction in long COVID monocytes as a critical driver of cardiovascular complications in PASC. Key defects-bioenergetic failure, impaired stress adaptation and mtDNA damage-correlate with clinical symptoms like heart failure and exercise intolerance. The stable elevation of mitochondrial membrane potential and resistance to ROS induction suggest maladaptive remodeling of mitochondrial physiology. These findings position mitochondrial resilience as a therapeutic target, with potential strategies including antioxidants, mtDNA repair agents or metabolic modulators. The dissociation between spike protein exposure and mitochondrial dysfunction highlights the need to explore host-directed mechanisms in PASC pathophysiology. This work advances our understanding of long COVID cardiovascular sequelae and provides a foundation for biomarker development and targeted interventions to mitigate long-term morbidity.},
}

Humans
*Monocytes/metabolism/pathology
*DNA, Mitochondrial/genetics/metabolism
*COVID-19/complications/metabolism/pathology
Male
Female
Middle Aged
*DNA Damage
Oxidative Stress
*Cardiovascular Diseases/metabolism/etiology/pathology
SARS-CoV-2
Membrane Potential, Mitochondrial
Reactive Oxygen Species/metabolism
Aged
Mitochondria/metabolism
*Energy Metabolism
Lipopolysaccharide Receptors/metabolism
Case-Control Studies

@article {pmid40428115,
year = {2025},
author = {Jiang, S and Loomba, J and Zhou, A and Sharma, S and Sengupta, S and Liu, J and Brown, D and On Behalf Of N C Consortium, },
title = {A Bayesian Survival Analysis on Long COVID and Non-Long COVID Patients: A Cohort Study Using National COVID Cohort Collaborative (N3C) Data.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
doi = {10.3390/bioengineering12050496},
pmid = {40428115},
issn = {2306-5354},
support = {75N95023D00001/TR/NCATS NIH HHS/United States ; },
abstract = {Since the outbreak of the COVID-19 pandemic in 2020, numerous studies have focused on the long-term effects of COVID infection. On 1 October 2021, the Centers for Disease Control (CDC) implemented a new code in the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) for reporting 'Post COVID-19 condition, unspecified (U09.9)'. This change indicated that the CDC recognized Long COVID as a real illness with associated chronic conditions. The National COVID Cohort Collaborative (N3C) provides researchers with abundant electronic health record (EHR) data by harmonizing EHR data across more than 80 different clinical organizations in the United States. This paper describes the creation of a COVID-positive N3C cohort balanced by the presence or absence of Long COVID (U09.9) and evaluates whether or not documented Long COVID (U09.9) is associated with decreased survival length.},
}

@article {pmid40427869,
year = {2025},
author = {Joseph, G},
title = {The Impact of Physical Activity on Long COVID Symptoms Among College Students: A Retrospective Study.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {5},
pages = {},
doi = {10.3390/ijerph22050754},
pmid = {40427869},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/epidemiology ; Retrospective Studies ; *Exercise ; Male ; *Students/statistics & numerical data ; Female ; Universities ; Cross-Sectional Studies ; Young Adult ; Adult ; SARS-CoV-2 ; Adolescent ; },
abstract = {Millions worldwide suffer from long COVID, which affects daily life and impairs multiple organs. Younger adults report symptoms more frequently than older adults. Since physical activity enhances overall health, this study examines whether regular exercise reduces long COVID severity in college students. This cross-sectional retrospective study surveyed 309 teacher-training college students about their long COVID symptoms and physical activity levels. Participants were categorized based on activity levels, and symptom differences were analyzed. Among respondents, 44 (14.4%) reported long COVID symptoms, with fatigue being the most common (13.3%). Students engaging in regular, intense physical activity did not experience fewer symptoms than less active students (1.83 ± 0.85; 1.75 ± 0.89, p = 0.376). However, physical education students reported fewer symptoms than students in other programs (6.7% vs. 17.4%). Greater self-reported participation in physical activity was not associated with less reported long COVID symptoms among college-aged students; however, students enrolled in physical education programs-who integrate physical activity into their daily routines as part of their academic curriculum-reported fewer symptoms, suggesting that sustained, structured physical activity may contribute to reduced symptom burden. Further research is needed to explore this relationship.},
}

Humans
*COVID-19/epidemiology
Retrospective Studies
*Exercise
Male
*Students/statistics & numerical data
Female
Universities
Cross-Sectional Studies
Young Adult
Adult
SARS-CoV-2
Adolescent

@article {pmid40427844,
year = {2025},
author = {Sommer, SB and Dietrich, MS and Barroso, JV},
title = {The Development and Initial Validation of the Memorial Symptom Assessment Scale-Long COVID (MSAS-LC): A Promising Tool for Measuring Long COVID.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {5},
pages = {},
doi = {10.3390/ijerph22050728},
pmid = {40427844},
issn = {1660-4601},
support = {//Julia Eleanor Blair Chenault Endowed Chair, Vanderbilt University School of Nursing/ ; },
mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; *Symptom Assessment/methods ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Prevalence ; Severity of Illness Index ; United States/epidemiology ; Reproducibility of Results ; },
abstract = {Long COVID remains a public health challenge, impacting over 65 million people globally and manifesting as persistent, multisystemic symptoms that complicate both diagnosis and treatment. To address the need for a standardized, patient-centered assessment tool, this study introduces the Memorial Symptom Assessment Scale-Long COVID (MSAS-LC), which evaluates symptom prevalence, frequency, severity, and distress. The MSAS-LC was developed by modifying the Memorial Symptom Assessment Scale to include 45 prevalent Long COVID symptoms. A cross-sectional survey of 261 U.S. adults (129 with Long COVID and 131 without) assessed validity and group differences. Symptom prevalence was analyzed using logistic regression, while symptom burden (frequency, severity, and distress) was compared using generalized linear models. Participants with Long COVID reported significantly higher symptom prevalence and burden across all systems. Memory problems (73.4% vs. 30.5%; OR = 6.29, p < 0.001) and post-exertional fatigue (OR = 8.55, p < 0.001) were among the most burdensome symptoms. These findings offer preliminary evidence supporting the potential utility of MSAS-LC and underscore the continued public health relevance of individual and collective symptom presentations. The findings suggest the distinct symptom burden, emphasizing the importance of future research to inform diagnostic and treatment strategies. With continued validation, the MSAS-LC may contribute to improved symptom monitoring and care planning in clinical and public health settings.},
}

Humans
*COVID-19/diagnosis/epidemiology
Male
Female
Middle Aged
Adult
Cross-Sectional Studies
Aged
*Symptom Assessment/methods
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Prevalence
Severity of Illness Index
United States/epidemiology
Reproducibility of Results

@article {pmid40426703,
year = {2025},
author = {Rudroff, T},
title = {Digital Biomarkers and AI for Remote Monitoring of Fatigue Progression in Neurological Disorders: Bridging Mechanisms to Clinical Applications.},
journal = {Brain sciences},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/brainsci15050533},
pmid = {40426703},
issn = {2076-3425},
abstract = {Digital biomarkers for fatigue monitoring in neurological disorders represent an innovative approach to bridge the gap between mechanistic understanding and clinical application. This perspective paper examines how smartphone-derived measures, analyzed through artificial intelligence methods, can transform fatigue assessment from subjective, episodic reporting to continuous, objective monitoring. The proposed framework for smartphone-based digital phenotyping captures passive data (movement patterns, device interactions, and sleep metrics) and active assessments (ecological momentary assessments, cognitive tests, and voice analysis). These digital biomarkers can be validated through a multimodal approach connecting them to neuroimaging markers, clinical assessments, performance measures, and patient-reported experiences. Building on the previous research on frontal-striatal metabolism in multiple sclerosis and Long-COVID-19 patients, digital biomarkers could enable early warning systems for fatigue episodes, objective treatment response monitoring, and personalized fatigue management strategies. Implementation considerations include privacy protection, equity concerns, and regulatory pathways. By integrating smartphone-derived digital biomarkers with AI analysis approaches, the future envisions fatigue in neurological disorders no longer as an invisible, subjective experience but rather as a quantifiable, treatable phenomenon with established neural correlates and effective interventions. This transformative approach has significant potential to enhance both clinical care and the research for millions affected by disabling fatigue symptoms.},
}

@article {pmid40423990,
year = {2025},
author = {Gross, RS and Carmilani, M and Stockwell, MS},
title = {Long COVID in Young Children, School-Aged Children, and Teens.},
journal = {JAMA pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamapediatrics.2025.1415},
pmid = {40423990},
issn = {2168-6211},
}

@article {pmid40420202,
year = {2025},
author = {Maeda, H and Igarashi, A and Kuwamitsu, O and Morimoto, K},
title = {Comparison of long-term health-related quality of life and symptoms between COVID-19 patients and test-negative controls during the Omicron-predominant period in Japan.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {136},
pmid = {40420202},
issn = {0778-7367},
support = {21HA2008, 23HA2017//the Ministry of Health, Labour and Welfare/ ; },
abstract = {BACKGROUND: Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affect health-related quality of life (HRQoL) and impose a substantial burden on society. While previous studies showed that both coronavirus disease 2019 (COVID-19) patients and patients with acute respiratory symptoms but negative for SARS-CoV-2 experienced persistent symptoms, evidence comparing the long-term HRQoL of COVID-19 patients with test-negative controls for SARS-CoV-2 remains limited. This study aimed to compare symptoms and HRQoL using EQ-5D-5L in both acute and chronic phases between COVID-19 patients and test-negative controls for SARS-CoV-2 during the Omicron-predominant period in Japan.

METHODS: Individuals aged ≥18 years tested for SARS-CoV-2 with COVID-19-like symptoms at a clinic in Tokyo, Japan, between January 2022 and January 2023, were invited an online survey. Individuals who tested positive and negative for SARS-CoV-2 were both included. Participants retrospectively recorded their physical and mental symptoms, and completed EQ-5D-5L questionnaires during the acute phase, and at months 1, 3, and 6, which were compared between COVID-19 patients and test-negative controls. Additionally, the mean EQ-5D-5L utility score was compared between male and female COVID-19 patients.

RESULTS: A total of 302 COVID-19 patients and 77 test-negative controls were included (median age: 42 years; 41.2% male; 13.2% with underlying medical conditions). At month 3, 19.9% (60/302) of COVID-19 patients and 9.1% (7/77) of test-negative controls reported ongoing symptoms. Mental symptoms and fatigue persisted for over three months among COVID-19 patients. The mean EQ-5D-5L utility score during the acute phase for COVID-19 patients was 0.615 (95% confidence interval [CI]: 0.586-0.645), and 0.874 (95% CI: 0.826-0.921) for test-negative controls, with a mean difference of -0.258 (95% CI: -0.324 to -0.193). COVID-19 patients consistently exhibited lower EQ-5D-5L utility scores than controls for over six months post-infection. Female COVID-19 patients showed lower EQ-5D-5L utility scores compared to male patients throughout the period (acute phase mean difference: -0.091; 95% CI: -0.151 to -0.031).

CONCLUSIONS: COVID-19 patients experienced more symptoms three months post-testing compared to test-negative controls, with lower EQ-5D-5L utility scores persisting for over six months. Female COVID-19 patients exhibited lower EQ-5D-5L utility scores than their male counterparts throughout the period.},
}

@article {pmid40420038,
year = {2025},
author = {Vieira, YP and Camilo, LDS and Araújo, ÉS and de Macedo Neto, JD and Junqueira, LL and Machado, KP and Gonzalez, TN and Neves, RG and Duro, SMS and Saes, MO},
title = {Inequalities in worsening work and income decrease/cessation in SARS-CoV-2 infection in adults and elderly people: the population-based SulCovid-19 study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {1946},
pmid = {40420038},
issn = {1471-2458},
mesh = {Humans ; *COVID-19/epidemiology/economics ; Female ; Male ; Cross-Sectional Studies ; Aged ; Middle Aged ; Brazil/epidemiology ; Adult ; *Income/statistics & numerical data ; Socioeconomic Factors ; SARS-CoV-2 ; },
abstract = {OBJECTIVE: To evaluate inequalities in the worsening of work and income decrease/cessation among adults and elderly people with COVID-19 in the extreme south of Brazil.

METHODS: This is a cross-sectional study based on the SulCovid-19 study carried out with adults and elderly people infected with SARS CoV-2 from December/2020 to March/2021 in the municipality of Rio Grande, RS, Brazil. The outcomes were: "worsening of work" and "income decrease/cessation" following COVID-19. The independent variables were gender, skin color, income, education, health insurance, age, marital status, schooling, morbidities, hospitalization and long COVID.

RESULTS: prevalence of worsening work was 33.7% (95%CI 31.8; 35.5), while prevalence of income decrease/cessation was 44.6% (95%CI 42.7; 46.6). Female individuals with income in dollars between US0.00 and US192.0 had 13.0% (95% CI 1.01; 1.27) and 22.0% (95% CI 1.02; 1.46) greater prevalence of losing work and were 22.0% (95% CI 1.12; 1.34) and 49.0% (95% CI 1.31; 1.70) more likely to suffer a decrease/cessation of their income. Individuals with long COVID had 46.0% greater prevalence (95% CI 1.27; 1.68) of worsening at work and 24.0% (95% CI 1.13; 1.37) greater prevalence of income decrease/cessation when compared to those without the disease. Individuals with 3 symptoms or more had 86.0% (95% CI 1.58; 2.20) greater prevalence of worsening work and 47.0% (95% CI 1.31; 1.65) greater prevalence of income decrease/cessation when compared to those without long COVID symptoms.

CONCLUSIONS: There was inequality in the worsening of work and income decrease/cessation for individuals infected with SARS CoV-2. Among these individuals, females, lower income, low education and greater long COVID severity were the most affected.},
}

Humans
*COVID-19/epidemiology/economics
Female
Male
Cross-Sectional Studies
Aged
Middle Aged
Brazil/epidemiology
Adult
*Income/statistics & numerical data
Socioeconomic Factors
SARS-CoV-2

@article {pmid40417395,
year = {2025},
author = {Barros-Aragão, FGQ and Pinheiro, TL and Pinto, TP and Vanderborgh, B and Rezende, NBS and de Freitas, GB and de Freitas, GR and Bozza, FA and Souza, AS and Rodrigues, EC and Brandão, CO and Mattos, P and Sudo, FK and Tovar-Moll, FF and De Felice, FG},
title = {Comparison of cerebrospinal fluid biomarkers in patients with severe COVID-19 neurological outcomes and Alzheimer's disease.},
journal = {Brain, behavior, & immunity - health},
volume = {46},
number = {},
pages = {101007},
pmid = {40417395},
issn = {2666-3546},
abstract = {BACKGROUND: COVID-19 induces acute and long-term neurological symptoms. Links between COVID-19 neurological disturbance and Alzheimer's disease (AD) have been hypothesized because neuroinflammation plays a significant role in both diseases. However, it is unknown if COVID-19 patients with neurological disturbance present molecular alterations related to AD pathology. A better understanding of possible molecular links between COVID-19-induced neurological disease and AD would lead to improved patient follow-up and late-onset disease prevention. Here, we analyze early AD biomarkers in a Brazilian cohort of COVID-19 patients with neurological symptoms. We compared COVID-19 patients' neuroinflammatory and AD biomarker levels to controls, amnestic mild cognitive impairment (aMCI), and AD.

METHODS: We analyzed cerebrospinal (CSF) biomarkers of neuroinflammation (interleukin-6 (IL6)), amyloid-beta (Aβ) proteinopathy (Aβ42/40), phosphorylated Tau (pTau181), and the neurodegeneration-associated biomarker total Tau in controls (n = 36), COVID-19 patients presenting neurological alterations (n = 35), aMCI (n = 19), and AD patients (n = 20). Comparisons were corrected by possible sex, age, and comorbidities confounding effects. CSF biomarkers were correlated with systemic and neuro-inflammation markers.

RESULTS: We found that severe COVID-19 patients presented higher CSF Tau than controls, comparable to alterations observed in AD patients. However, we did not find changes in CSF Aβ42/40, pTau-181/Aβ42, or Tau/Aβ42 ratios. Severe COVID-19 patients presented higher Tau, Tau/Aβ42, and pTau181/Aβ42 than mild patients. In COVID-19 patients, CSF pro-inflammatory cytokine IL6 and AD biomarkers correlated with systemic inflammatory index (SII).

CONCLUSIONS: Collectively, our findings reveal that CSF tau levels are comparably elevated in COVID-19 neurological patients and AD, suggesting ongoing neurodegeneration in COVID-19 neurological disease, but no biomarker alterations related to AD pathology. Furthermore, CNS AD-related biomarker levels in COVID-19 patients change in association with disease severity and systemic inflammation. Considering that inflammation may persist post-COVID, our findings urge the assessment of possible AD-related biomarker changes in COVID-19 survivors with lingering symptoms.},
}

@article {pmid40416973,
year = {2025},
author = {Luo, Q and Song, Q and Li, Y and Zong, K and Liu, T and He, J and Mei, G and Du, H and Xia, Z and Liu, M and Song, J and Gao, C and Xia, D and Xue, G and Tian, W and Qu, Y and Kou, Z and Dong, Z and Han, J},
title = {Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1596065},
pmid = {40416973},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/virology ; Aged ; *SARS-CoV-2/immunology ; *Antibodies, Neutralizing/immunology/blood ; Female ; Male ; *Antibodies, Viral/immunology/blood ; Middle Aged ; Aged, 80 and over ; Immunologic Memory ; B-Lymphocytes/immunology ; Th17 Cells/immunology ; Memory B Cells/immunology ; },
abstract = {OBJECTIVES: To evaluate the immune persistence and cross-immune response of elderly individuals after Omicron BA.5 infections.

METHOD: The neutralizing antibodies against WT, BA.5, XBB.1 and EG.5 strains were analyzed. The T/B-cell subsets' responses were tested through intracellular cytokine staining and flow cytometry.

RESULTS: The neutralizing antibodies titers against WT and BA.5 strain, remaining high level for at least 6 months, were higher than that of both XBB.1 and EG.5 variants. The neutralizing antibodies of WT, BA.5, XBB.1, and EG.5 strains in the elderly were slightly lower than those in middle-age. The memory B cells decreased rapidly in the elderly, and Tfh, Th17 cells of the elderly continued to increase for only 3 months, while Tfh and Th17 cells increased in the middle-aged for over 6 months. For the elderly, after peptide stimulation, unswitched/switched memory B cells decreased, while double negative B cells displayed higher proliferation. The proportions of both naïve and Temra cells in CD4[+] and CD8[+] T cells declined, whereas those of Tcm and Tem cells elevated. In the meantime, both CD69[+] and CD38[+] T cells decreased, but the frequencies of PD-1[+] and CTLA-4[+] of CD4[+] and CD8[+] T cells showed an increasing trend. The proportions of PD-1[+] and CTLA-4[+] cells also increased in older people with long COVID symptoms at 3m post-infection.

CONCLUSIONS: Omicron BA.5 infection induced lower neutralizing antibodies against XBB.1 and EG.5 variant. The decrease of memory B cells, CD69[+] and CD38[+]T cells, as well as the increase of PD-1[+], CTLA-4[+] of CD4[+]/CD8[+]T cells and double negative B cells, indicate that sustained immune responses against BA.5 infection may wane more rapidly in elderly populations.},
}

Humans
*COVID-19/immunology/virology
Aged
*SARS-CoV-2/immunology
*Antibodies, Neutralizing/immunology/blood
Female
Male
*Antibodies, Viral/immunology/blood
Middle Aged
Aged, 80 and over
Immunologic Memory
B-Lymphocytes/immunology
Th17 Cells/immunology
Memory B Cells/immunology

@article {pmid40416618,
year = {2025},
author = {Eltayeb, A and Adilović, M and Golzardi, M and Hromić-Jahjefendić, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM},
title = {Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19429},
pmid = {40416618},
issn = {2167-8359},
mesh = {Humans ; *COVID-19/complications ; *Thrombosis/virology/metabolism/etiology ; *SARS-CoV-2 ; *Coronavirus Nucleocapsid Proteins/metabolism ; },
abstract = {COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis-key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.},
}

Humans
*COVID-19/complications
*Thrombosis/virology/metabolism/etiology
*SARS-CoV-2
*Coronavirus Nucleocapsid Proteins/metabolism

@article {pmid40416333,
year = {2025},
author = {Beck, E and Joshi, K and Mehta, D and Lorenc, S and Rizkalla, B and Van de Velde, N},
title = {Workplace Vaccination Against COVID-19 and Seasonal Influenza in the United States: A Modeling-Based Estimation of the Health and Economic Benefits for Employers and Employees.},
journal = {Journal of market access & health policy},
volume = {13},
number = {2},
pages = {17},
pmid = {40416333},
issn = {2001-6689},
abstract = {The objectives were to assess the economic burden of COVID-19 and impact of workplace COVID-19 vaccination in the United States (US). An economic model estimated COVID-19 workplace burden (infections, long COVID, inpatient/outpatient care, absent days) with and without vaccination, compared with seasonal influenza vaccination for context, using Optum's de-identified Clinformatics[®] Data Mart Database. Without workplace vaccination, an average US business (with 10,000 employees), had 18,175 absent days from COVID-19 and lost productivity costs of USD 5.08 million. Implementing COVID-19 workplace vaccination (at 70% coverage) prevented approximately 3132 absent days, saving employers USD 876,453 (lost productivity) and USD 240,633 (medical costs); and saving employees USD 182,196 (medical costs) and USD 198,250 (lost wages) versus no COVID-19 workplace vaccination. The burden and vaccination impact were greater for COVID-19 versus seasonal influenza. Workplace vaccination for COVID-19 and seasonal influenza can have a significant impact for both the employer and employees through averted disease.},
}

@article {pmid40416015,
year = {2025},
author = {Harabuchi, Y and Kumai, T and Nishi, K and Tanaka, A and Hotta, O and Hagino, H and Kusuyama, T and Mogitate, M and Ohno, Y and Sakakibara, A and Araki, S and Nishida, Y and Shintani, T and Takezawa, H and Ito, H and Komazawa, D and Nishiwaki, N and Toritani, R and Hirahata, K and Marumo, S},
title = {Retracted: Chronic Epipharyngitis Treated with Epipharyngeal Abrasion Therapy: Symptoms, Diagnosis, Pathogenesis, and Treatment Outcomes.},
journal = {JMA journal},
volume = {8},
number = {2},
pages = {371-384},
pmid = {40416015},
issn = {2433-3298},
abstract = {Chronic epipharyngitis is associated with a wide variety of symptoms, including local symptoms such as postnasal drip, sore throat, lump sensation of the pharynx, headache, chronic cough, nasal obstruction, tinnitus/ear fullness, chronic phlegm and dysphonia due to inflammation of the epipharynx, functional somatic symptoms such as chronic fatigue, dizziness, insomnia, brain fog, abdominal discomfort, and depression caused by dysfunction of the hypothalamus-limbic system via disturbances of vagal response and cerebrospinal fluid outflow, and distant organ symptoms such as immunoglobulin A nephropathy and palmoplantar pustulosis caused by the epipharyngeal lymphoid tissue as an etiologic organ. In the past, chronic inflammation in the epipharynx was difficult to prove by gross findings, now, direct observation of the epipharyngeal inflammation by endoscopy has become easier for the diagnosis. For the treatment of chronic epipharyngitis, epipharyngeal abrasive therapy (EAT), epipharyngeal application of a 1% zinc chloride solution intranasally or orally was popular since the 1960s, recently, endoscopic EAT (E-EAT), in which epipharynx is safely and accurately observed and abraded under clear vision using an endoscope, has been developed. The mechanisms of EAT effects can be classified into anti-inflammatory/antiviral effect, bloodletting effect, and vagus nerve stimulation effect. Recently, the effectiveness of EAT for post-acute sequelae of coronavirus disease 2019 (COVID-19), known as long COVID, has come into the limelight, and the number of patients for whom EAT is expected to increase. In 2019, the Japan Society of Stomato-pharyngology established the EAT Review Committee to accumulate evidence on the efficacy of EAT and to establish indications and techniques for its use. In this article, the EAT Review Committee outlines its symptoms, pathogenesis, and diagnosis of chronic epipharyngitis, technique of E-EAT, mechanisms of EAT effects, past reports for the efficacy of EAT, and a multicenter prospective study.},
}

@article {pmid40415285,
year = {2025},
author = {Eltayeb, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM},
title = {Intrinsic Factors Behind Long COVID: VI. Combined Impact of G3BPs and SARS-CoV-2 Nucleocapsid Protein on the Viral Persistence and Long COVID.},
journal = {Journal of cellular biochemistry},
volume = {126},
number = {5},
pages = {e70038},
doi = {10.1002/jcb.70038},
pmid = {40415285},
issn = {1097-4644},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/virology/metabolism/immunology/pathology ; *SARS-CoV-2/metabolism/physiology ; *Coronavirus Nucleocapsid Proteins/metabolism ; *RNA Recognition Motif Proteins/metabolism/immunology ; *Poly-ADP-Ribose Binding Proteins/metabolism/immunology ; *DNA Helicases/metabolism ; *Phosphoproteins/metabolism ; *RNA Helicases/metabolism ; Virus Replication ; Stress Granules/metabolism/virology ; Host-Pathogen Interactions ; },
abstract = {The efficient transmission of SARS-CoV-2 caused the COVID-19 pandemic, which affected millions of people around the globe. Despite extensive efforts, specific therapeutic interventions and preventive measures against COVID-19 and its consequences, such as long COVID, have not yet been identified due to the lack of a comprehensive knowledge of the SARS-CoV-2 biology. Therefore, a deeper understanding of the sophisticated strategies employed by SARS-CoV-2 to bypass the host antiviral defense systems is needed. One of these strategies is the inhibition of the Ras GTPase-activating protein-binding protein (GAP SH3-binding protein or G3BP)-dependent host immune response by the SARS-CoV-2 nucleocapsid (N) protein. This inhibition disrupts the formation of stress granules (SGs), which are crucial for antiviral defense. By preventing SG formation, the virus enhances its replication and evades the host's immune response, leading to increased disease severity. Given the involvement of G3BP1 in SG formation and its ability to interact with viral proteins, along with the crucial role of the N protein in the replication of the virus, we hypothesize that these proteins may have a potential role in the pathogenesis of long COVID. Despite the current lack of direct evidence linking these proteins to long COVID, their interactions and functions suggest a possible connection that warrants further investigation.},
}

Humans
*COVID-19/virology/metabolism/immunology/pathology
*SARS-CoV-2/metabolism/physiology
*Coronavirus Nucleocapsid Proteins/metabolism
*RNA Recognition Motif Proteins/metabolism/immunology
*Poly-ADP-Ribose Binding Proteins/metabolism/immunology
*DNA Helicases/metabolism
*Phosphoproteins/metabolism
*RNA Helicases/metabolism
Virus Replication
Stress Granules/metabolism/virology
Host-Pathogen Interactions

@article {pmid40414164,
year = {2025},
author = {Keith, S and Hill, G and Smith, A and Brechin, D and Mustafa, R and Antunes, G and Swanson, V},
title = {Identifying the prevalence of symptoms of anxiety and depression in patients with post COVID.},
journal = {Journal of psychosomatic research},
volume = {194},
number = {},
pages = {112147},
doi = {10.1016/j.jpsychores.2025.112147},
pmid = {40414164},
issn = {1879-1360},
}

@article {pmid40413391,
year = {2025},
author = {Reis, N and Dias, MJC and Sousa, L and Oliveira, J and Rico, MT and Baixinho, CL and Henriques, MA},
title = {Respiratory telerehabilitation: user experience and satisfaction with the program.},
journal = {BMC geriatrics},
volume = {25},
number = {1},
pages = {372},
pmid = {40413391},
issn = {1471-2318},
mesh = {Humans ; Aged ; *Telerehabilitation ; Male ; Female ; *Pulmonary Disease, Chronic Obstructive/rehabilitation/psychology ; *Patient Satisfaction ; *COVID-19/epidemiology ; Aged, 80 and over ; Qualitative Research ; Portugal ; Telemedicine ; },
abstract = {BACKGROUND: The rise of telehealth in geriatric care is an inexorable movement toward adapting to global digitalization trends, in terms of both technology and implementation experiences, with clear gains for health systems and citizens. A literature review shows that the older population, with lower levels of digital literacy, faces specific challenges with this type of service. The aim of this study was to understand the way older people with Chronic Obstructive Pulmonary Disease or long COVID perceive the implementation of telerehabilitation programs to meet their healthcare needs.

METHODS: A qualitative study was conducted using semi-structured interviews to answer the research question: How do older people perceive telerehabilitation programs? The study participants were 17 people aged ≥ 65 years old who had completed a respiratory telerehabilitation program at a Portuguese hospital. The interviews were submitted to content analysis using WebQDA[®] qualitative data analysis software.

RESULTS: The study participants had an average age of 70.94 ± 7.44 years old. The content of the interviews with these older people points to easy adaptation to the telerehabilitation program. Three categories and their respectives subcategories emerged from the content analysis: (1) access and continuity of care (access, continuity of care, and self-management); (2) presence (communication with the team and maintaining relationships); and (3) experience in the program (comfort, advantages, and difficulties).

CONCLUSIONS: This study allows for an understanding of how older people perceive participation in telerehabilitation programs, what they value, and the difficulties they experience. It makes it possible to make recommendations for clinic practice and research into this emerging area of health care.},
}

Humans
Aged
*Telerehabilitation
Male
Female
*Pulmonary Disease, Chronic Obstructive/rehabilitation/psychology
*Patient Satisfaction
*COVID-19/epidemiology
Aged, 80 and over
Qualitative Research
Portugal
Telemedicine

@article {pmid40412913,
year = {2025},
author = {DeMasi, M and Bujold, L},
title = {Effect of the Covid Pandemic on Women's Health.},
journal = {Primary care},
volume = {52},
number = {2},
pages = {371-382},
doi = {10.1016/j.pop.2025.01.009},
pmid = {40412913},
issn = {1558-299X},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Women's Health ; United States/epidemiology ; SARS-CoV-2 ; Pandemics ; },
abstract = {The corona virus disease 2019 (COVID-19) pandemic impacted all spheres of the lives of women. This article focuses on the impact on the health, careers, and family lives of women in the United States. There is a lasting impact from COVID-19 on the lives and health of women. Preventative care and chronic care were disrupted. Long covid seems to impact premenopausal women at much higher rates than men. Time spent between work and home changed for many during the pandemic. Women shifted to more time spent on home duties. The long-term outcome of career advancement and economic success is unknown.},
}

Humans
*COVID-19/epidemiology
Female
*Women's Health
United States/epidemiology
SARS-CoV-2
Pandemics

@article {pmid40412098,
year = {2025},
author = {Franco-Moreno, A and Torres-Macho, J},
title = {Long COVID.},
journal = {Medicina clinica},
volume = {165},
number = {2},
pages = {107009},
doi = {10.1016/j.medcli.2025.107009},
pmid = {40412098},
issn = {1578-8989},
}

@article {pmid40410115,
year = {2025},
author = {Tsai, TY and Kao, JH and Wei, SC},
title = {Reply to "Comment on "Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from Taiwan"".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2025.05.023},
pmid = {40410115},
issn = {0929-6646},
}

@article {pmid40408228,
year = {2025},
author = {Berwick, RJ and Sahbaie, P and Kenny, G and Guo, TZ and Neiland, H and Andersson, DA and Clark, JD and Mallon, P and Goebel, A},
title = {Postacute COVID-19 syndrome and fibromyalgia syndrome are associated with anti-satellite glial cell IgG serum autoantibodies but only fibromyalgia syndrome serum-IgG is pronociceptive.},
journal = {Pain},
volume = {},
number = {},
pages = {},
pmid = {40408228},
issn = {1872-6623},
support = {22976/VAC_/Versus Arthritis/United Kingdom ; PhD Fees//Pain Relief Foundation/ ; 21544/VAC_/Versus Arthritis/United Kingdom ; MR/S003428/1/MRF_/MRF_/United Kingdom ; MR/S003428/1/MRC_/Medical Research Council/United Kingdom ; 21544/VAC_/Versus Arthritis/United Kingdom ; },
abstract = {Postacute COVID-19 syndrome (PACS) describes the persistence of symptoms following severe acute respiratory syndrome coronavirus 2 clearance. PACS is sometimes associated with pain and fatigue resembling fibromyalgia syndrome (FMS). Severe FMS has recently been associated with pronociceptive immunoglobulin G (IgG) autoantibodies and anti-satellite glial cell (SGC) IgG autoreactivity, suggesting an autoimmune aetiology. We validated FMS-IgG passive transfer and then tested the hypothesis that PACS-patients, with high musculoskeletal pain and fatigue, harbour proalgesic and anti-SGC autoantibodies. PACS-patients with high pain and fatigue or people recently recovered from acute COVID-19 were recruited to the All-Ireland Infectious Diseases Study. We pooled serum from 18 patients per group and purified their serum-IgG. In addition, we obtained IgG from UK patients with FMS and healthy controls to confirm assay performance. Passive transfer experiments of IgG (8 mg/d) over 3 days were conducted using male (C57BL/6J) mice (n = 6 mice per group). We measured mechanical and cold hypersensitivities and grip strength. Injection of FMS-IgG elicited the previously described mouse phenotype in male rodents, including increased mechanical/cold hypersensitivities and reduced grip strength compared with control IgG, whereas pooled PACS-IgG was inert. Immunocytochemistry of primary-SGC-enriched cultures reproduced the increased staining of FMS-IgG over the control reported previously. Both IgG from patients with PACS and those recently recovered from COVID-19 stained strongly positive. We confirm the pronociceptive properties of FMS-IgG and demonstrate, in contrast, that PACS symptoms from our cohort, with severe pain and fatigue, are not transmissible through passive transfer to male rodents. Postacute COVID-19 syndrome pain is often localised, and stratification according to the widespread distribution of pain should be considered for future studies; recovered COVID-19 leaves a strong trace of anti-SGC autoreactivity.},
}

@article {pmid40407658,
year = {2025},
author = {Park, SO and Nanda, N},
title = {Long COVID: A Systematic Review of Preventive Strategies.},
journal = {Infectious disease reports},
volume = {17},
number = {3},
pages = {},
pmid = {40407658},
issn = {2036-7430},
abstract = {Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking. Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms. Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC. Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID.},
}

@article {pmid40406601,
year = {2025},
author = {Lugo, ZR and Patiño-Torres, MJ},
title = {Editorial: Neuropsychiatric consequences of the COVID-19 pandemic: understanding mechanisms, risk factors, and treatment.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1611176},
pmid = {40406601},
issn = {1662-5161},
}

@article {pmid40406371,
year = {2025},
author = {Jacka, BP and Cheng, QL and Schiavone, B and Darley, DR and Kelleher, AD and Dore, GJ and Matthews, GV},
title = {Trajectories of Health-Related Quality of Life 2 Years After Mild/Moderate Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the Pre-Omicron Era.},
journal = {Open forum infectious diseases},
volume = {12},
number = {5},
pages = {ofaf142},
pmid = {40406371},
issn = {2328-8957},
abstract = {BACKGROUND: Individuals with postacute sequelae of coronavirus disease 2019 (COVID-19), or long COVID, experience substantial burden of illness many months after initial infection. Few studies have comprehensively and longitudinally assessed health outcomes for people with long COVID following mild/moderate infection. We applied the Wilson-Cleary model of health-related quality of life (HRQOL) to describe the impact of long COVID on multiple health dimensions up to 24 months following mild/moderate COVID-19.

METHODS: Participants within the ADAPT post-COVID study (N = 172, 86% mild/moderate infection) completed structured patient-reported outcome measures at 4, 8, 12, 18, and 24 months postinfection. Following the Wilson-Cleary model, questionnaires assessed symptoms (anxiety/depression, chronic fatigue, breathlessness), return to pre-COVID-19 functioning, perceived health status (EuroQol Visual Analogue Scale), and wellbeing (EuroQol EQ-5D-5L, Personal Wellbeing Index). Temporal trends were assessed using general estimating equations and ordinal logistic regression, including time × long COVID interactions.

RESULTS: Thirty-seven percent of participants were diagnosed with long COVID (≥1 new/persisting symptoms of chest pain, breathlessness, or fatigue/malaise at least 12 weeks after infection). Long COVID was associated with poorer health outcomes across all domains at first assessment. Over 2 years, participants with long COVID reported improvement in return to pre-COVID-19 work and Somatic and Psychological Health Report chronic fatigue but sustained impairment was observed in all other health domains, compared to participants recovered from COVID-19.

CONCLUSIONS: Substantial long-term impairment in various health domains were observed for individuals with long COVID following mild/moderate initial infection, with little improvement over time in most. Multimodal interventions must address impairment in multiple domains of HRQOL in individuals with long COVID.},
}

@article {pmid40405092,
year = {2025},
author = {Seo, YB and Choi, YJ and Seo, JW and Kim, EJ and Lee, J and Song, JY},
title = {Therapeutic options for the treatment of post-acute sequelae of COVID-19: a scoping review.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {731},
pmid = {40405092},
issn = {1471-2334},
support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; },
mesh = {Humans ; Antiviral Agents/therapeutic use ; *COVID-19/complications/therapy ; *COVID-19 Drug Treatment ; Hyperbaric Oxygenation ; *Post-Acute COVID-19 Syndrome/therapy ; },
abstract = {OBJECTIVES: This scoping review aimed to summarize the available studies to address the question of which therapeutic agents can be utilized for patients with post-acute sequelae of COVID-19 (PASC).

METHODS: We conducted a systematic search in medical databases, including PubMed and Embase, for studies aligned with our objectives published between January 1, 2020, and July 22, 2024. For each study, we summarized the main symptoms targeted, study design, therapeutic regimens, evaluation tools, and clinical outcomes.

RESULTS: A total of 413 studies were identified, and 39 studies were included in this review based on relevance to the research objectives. We primarily focused on high-level evidence studies, such as meta-analyses and randomized controlled trials, but observational studies were included when evidence was scarce. Therapeutic agents evaluated included hyperbaric oxygen, ivermectin, metformin, naltrexone, micronutrient supplements, antifibrotic agents, antiviral agents, and selective serotonin reuptake inhibitors (SSRIs). Among these, hyperbaric oxygen, antifibrotic agents, antiviral agents, and SSRIs demonstrated promising results. However, the heterogeneity of PASC symptoms posed challenges in synthesizing findings for specific symptom-based outcomes.

CONCLUSION: Given the heterogeneity of symptoms, this review highlights the need for standardized and targeted research to better address the diverse therapeutic needs of patients with PASC.

CLINICAL TRIAL: Not applicable.},
}

Humans
Antiviral Agents/therapeutic use
*COVID-19/complications/therapy
*COVID-19 Drug Treatment
Hyperbaric Oxygenation
*Post-Acute COVID-19 Syndrome/therapy

@article {pmid40404198,
year = {2025},
author = {Puhan, MA and Dalla Lana, K},
title = {Rehabilitation for persons with long COVID beyond the recovery phase of SARS-CoV-2 infection.},
journal = {The European respiratory journal},
volume = {65},
number = {5},
pages = {},
doi = {10.1183/13993003.00239-2025},
pmid = {40404198},
issn = {1399-3003},
}

@article {pmid40404195,
year = {2025},
author = {Yonker, LM and Kane, B and Pretorius, E and Putrino, D and McFarland, S and Brodin, P and Zimmerman, KO and Munblit, D and Rowe, PC and Vos, T and Warburton, D and Stephenson, T and Buonsenso, D and , },
title = {Equity in research: a global consensus statement on the urgency of including children in long COVID clinical trials.},
journal = {The European respiratory journal},
volume = {65},
number = {5},
pages = {},
pmid = {40404195},
issn = {1399-3003},
abstract = {Efforts are urgently needed to intentionally address this inequity in long COVID research to include children early in clinical trial design. https://bit.ly/3RMGmYz},
}

@article {pmid40404020,
year = {2025},
author = {Schreiber, CS and Ramil, LN and Bieligk, J and Meineke, R and Käufer, C and Richter, F},
title = {Intravenous SARS-CoV-2 Spike protein induces neuroinflammation and alpha-synuclein accumulation in brain regions relevant to Parkinson's disease.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbi.2025.05.021},
pmid = {40404020},
issn = {1090-2139},
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) frequently presents with neurological symptoms in human patients and leads to long-lasting brain pathology in a hamster model. There is no overt SARS-CoV-2 virus replication in central neurons. Whether viral proteins are sufficient to cause this pathology requires further investigations. The SARS-CoV-2 Spike-protein S1-subunit (S1-protein) has recently gained interest for causing neuroinflammation and accelerating aggregation of alpha-synuclein (aSyn) in vitro. Here, we show the impact of S1-protein in a broad spectrum of brain regions after injection via three different application routes in C57/BL6 mice.

METHODS: S1-protein was administered either intranasally, intravenously or intracerebrally. We quantified aSyn immunoreactivity and phosphorylated aSyn (pS129), microglia and astrocyte reactivity, ACE2/Neuropilin-1 receptor expression, and parvalbumin-positive interneurons in limbic system, basal ganglia, and cortical regions 14 days post-application. Plasma cytokine profiles were assessed 6 days post-injection.

RESULTS: While intracerebral injection resulted in decreased aSyn immunoreactivity with increased pS129 in males, intravenous injection led to increased levels of aSyn immunoreactivity and microglia cell density, predominantly in brain regions associated with Parkinson's disease pathology. Intranasal application of S1-protein induced microgliosis in some brain regions but resulted in sex-dependent alterations of aSyn levels, with increases in females and decreases in males. All routes showed sex-dependent alterations in astrocytic reactivity, receptor expression, and parvalbumin-positive interneurons.

CONCLUSION: Our results demonstrate that S1-protein itself leads to neuroinflammation, altered aSyn homeostasis, and disruption of inhibitory circuits in a route- and sex-dependent manner. These findings indicate the possibility of S1-protein being a crucial agent for both neuroinflammatory processes and altered protein regulation mechanisms. S1-protein trapped in tissue reservoirs could therefore explain symptoms occurring or persisting beyond viral clearance (Post COVID-19 condition).},
}

@article {pmid40403025,
year = {2025},
author = {Wander, PL and Lowy, E and Korpak, A and Beste, LA and Boyko, EJ},
title = {Association of long COVID documentation with clinical outcomes among Veterans with diabetes.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0324709},
pmid = {40403025},
issn = {1932-6203},
mesh = {Humans ; Female ; *COVID-19/epidemiology/complications/mortality ; Male ; *Veterans/statistics & numerical data ; Aged ; Retrospective Studies ; United States/epidemiology ; *Diabetes Mellitus/epidemiology ; Middle Aged ; Glycated Hemoglobin ; Documentation ; Hypoglycemic Agents/therapeutic use ; Electronic Health Records ; SARS-CoV-2/isolation & purification ; United States Department of Veterans Affairs ; Hospitalization/statistics & numerical data ; },
abstract = {OBJECTIVE: To examine public health impacts of Long COVID on long-term hyperglycemia and metabolic health.

MATERIALS & METHODS: We conducted a retrospective cohort study using US Veterans Health Administration electronic health records data to examine associations of Long COVID documentation (International Statistical Classification of Diseases, Tenth Revision code U09.9) with clinical outcomes (number of primary care visits, receipt of new classes of glucose-lowering medications, weight change, hemoglobin A1c, initiation of insulin, initiation of dialysis, hospitalization, and mortality) among U.S. Veterans with diabetes (1 October 2021-1 October 2023; n = 1,896,080).

RESULTS: Veterans were 69.7 years old on average at cohort entry, 6% female, and 1% had U09.9 documentation. Compared to Veterans without U09.9, those with U09.9 had 39% more primary care visits per year after the index date (incidence rate ratio [IRR] 1.36, 95%CI 1.36; 1.37), 21% more glucose-lowering medication classes added per year (IRR 1.21, 95%CI 1.18; 1.24), a 0.62 kg greater weight gain (95%CI 0.52; 0.72), a 0.10-point lower mean HbA1c (95%CI -0.12; -0.08), a 43% greater odds of starting insulin (odds ratio [OR] 1.43, 95%CI 1.32; 1.54), a 34% greater odds of starting dialysis (OR 1.34, 95%CI 1.11; 1.62), a 102% greater odds of VA hospitalization (OR 2.02, 95%CI 1.95; 2.09), and a 13% lower odds of mortality (OR 0.87, 95%CI 0.83; 0.91).

CONCLUSIONS: In Veterans with diabetes, Long COVID documentation was associated with greater medication use, odds of starting dialysis, and odds of hospitalization, but with lower odds of mortality. Individuals with Long COVID documentation did not have more weight gain or higher HbA1c, suggesting that adverse effects of Long COVID on medication changes and kidney function in persons with diabetes may be due to other factors. Future studies should examine mechanisms by which Long COVID might contribute to progression of kidney disease and more intensive diabetes treatment.},
}

Humans
Female
*COVID-19/epidemiology/complications/mortality
Male
*Veterans/statistics & numerical data
Aged
Retrospective Studies
United States/epidemiology
*Diabetes Mellitus/epidemiology
Middle Aged
Glycated Hemoglobin
Documentation
Hypoglycemic Agents/therapeutic use
Electronic Health Records
SARS-CoV-2/isolation & purification
United States Department of Veterans Affairs
Hospitalization/statistics & numerical data

@article {pmid40402473,
year = {2025},
author = {de Andrade, ML and do Monte, AL and Gerage, AM and Galliano, LM and Costa, EC and Ritti Dias, RM and Corrêa, FI},
title = {Effects of Physical Exercise on Functional Physical Performance in Individuals With Long COVID: A Systematic Review.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {},
number = {},
pages = {},
pmid = {40402473},
issn = {1932-751X},
abstract = {PURPOSE: To analyze the effect of physical exercise on functional parameters in individuals with long coronavirus disease-2019 (COVID-19).

REVIEW METHODS: A search in MEDLINE, EMBASE, Web of Science, Scielo, and EBSCO was carried out in October 2022, and it was updated in June 2024. For inclusion, studies should have involved physical training without pulmonary rehabilitation, have involved individuals who had long COVID-19, and were prospective trials, clinical trials, or controlled trials. Two reviewers independently performed data extraction and assessed the risk of bias. Seven studies were reviewed, three of high methodological quality. Participants with long COVID-19 were hospitalized in two studies. Interventions lasted 2 to 16 weeks, with frequencies of 2 to 7 days per week, often involving resistance exercise. Strength improved in 67% of studies, cardiorespiratory fitness in 50%, and agility/mobility in 60%. Anxiety improved in 25% of studies, while depression improved in 75%. Quality of life improved across all studies, with dyspnea and fatigue improving in 40% and 80%, respectively.

SUMMARY: Results suggest potential benefits of exercise training for subjects with long COVID-19 in several outcomes, mainly in functional capacity, depression symptoms, quality of life, and fatigue.},
}

@article {pmid40400892,
year = {2025},
author = {Ferrer, G and Valerio-Pascua, F and Alas-Pineda, C and Gaitán-Zambrano, K and Pavón-Varela, DJ},
title = {Intranasal Chlorpheniramine for Early Symptomatic Treatment of COVID-19 and the Impact on Long-COVID.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82736},
pmid = {40400892},
issn = {2168-8184},
abstract = {This review explores the therapeutic potential of intranasal chlorpheniramine maleate (iCPM) in managing both acute COVID-19 and Long COVID by integrating histamine H1 receptor antagonism and bitter taste receptor (T2R) activation. Current literature on histamine-mediated inflammation, T2R activation, and the dual-action mechanisms of iCPM were analyzed. Emphasis was placed on its antiviral, anti-inflammatory, and mucosal immunity-enhancing properties. iCPM demonstrates significant efficacy in addressing acute COVID-19 symptoms by inhibiting histamine-mediated inflammatory pathways and reducing cytokine storms. As a T2R agonist, it enhances mucosal immunity through nitric oxide production, mucociliary clearance, and antimicrobial peptide synthesis, reducing viral replication and supporting respiratory health. Additionally, iCPM shows promise in mitigating persistent symptoms of long COVID, including fatigue, brain fog, and respiratory dysfunction, by addressing chronic inflammation and residual viral activity. The integration of H1 receptor antagonism and T2R activation positions iCPM as a novel dual-target therapy for respiratory infections. Its localized delivery and broad mechanism of action make it a promising candidate for managing both the acute and chronic phases of COVID-19. Future research should focus on large-scale clinical trials and personalized approaches based on genetic variations in T2R pathways.},
}

@article {pmid40400794,
year = {2025},
author = {Shah, N and Patel, D and Sousa, A and Leder, AN},
title = {Changes in Migraine Headaches Following SARS-CoV-2 Infection: A Case Series.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82708},
pmid = {40400794},
issn = {2168-8184},
abstract = {During the COVID-19 pandemic, changes in migraine headaches have been observed. This case series of seven patients seeks to identify changes in migraines following COVID-19 infection and discuss the mechanisms by which these changes may have occurred. The study was composed of seven subjects with prior COVID-19 infection and a preceding history of migraine disorder. Most of the subjects presented with increased frequency and intensity of migraines shortly or immediately following COVID-19 infection. Many also described a shift in pain from local to diffuse headache. Additionally, some subjects developed other neuropsychiatric symptoms consistent with long COVID that included brain fog and, unusually, aphasia. After COVID-19 infection, six subjects had reduced efficacy for their medications and had to alter their regimen. Standard treatments such as Botox and anti-calcitonin gene-related peptide (anti-GCRP) had varied success among the cases. It is important to note that the pathophysiology of migraines during COVID-19 is still unclear and other factors can play a role. Nevertheless, individuals with a history of migraines noticed worsening symptoms and changes in medication efficacy following COVID-19 infection.},
}

@article {pmid40399555,
year = {2025},
author = {Lammi, V and Nakanishi, T and Jones, SE and Andrews, SJ and Karjalainen, J and Cortés, B and O'Brien, HE and Ochoa-Guzman, A and Fulton-Howard, BE and Broberg, M and Haapaniemi, HH and Kanai, M and Pirinen, M and Schmidt, A and Mitchell, RE and Mousas, A and Mangino, M and Huerta-Chagoya, A and Sinnott-Armstrong, N and Cirulli, ET and Vaudel, M and Kwong, ASF and Maiti, AK and Marttila, MM and Posner, DC and Rodriguez, AA and Batini, C and Minnai, F and Dearman, AR and Warmerdam, CAR and Sequeros, CB and Winkler, TW and Jordan, DM and Rešcenko, R and Miano, L and Lane, JM and Chung, RK and Guillen-Guio, B and Leavy, OC and Carvajal-Silva, L and Aguilar-Valdés, K and Frangione, E and Guare, L and Vergasova, E and Marouli, E and Striano, P and Zainulabid, UA and Kumar, A and Ahmad, HF and Edahiro, R and Azekawa, S and , and , and , and , and , and , and , and , and , and Luoh, SW and Erikstrup, C and Pedersen, OBV and Lerner-Ellis, J and Colombo, A and Grzymski, JJ and Ishii, M and Okada, Y and Beckmann, ND and Kumari, M and Wagner, R and Heid, IM and John, C and Short, PJ and Magnus, P and Ansone, L and Valenti, LVC and Lee, SA and Wain, LV and Verdugo, RA and Banasik, K and Geller, F and Franke, LH and Rakitko, A and Duncan, EL and Renieri, A and Tsilidis, KK and de Cid, R and Niavarani, A and Abner, E and Tusié-Luna, T and Verma, SS and Smith, GD and Timpson, NJ and Madduri, RK and Cho, K and Daly, MJ and Ganna, A and Schulte, EC and Richards, JB and Ludwig, KU and Marks-Hultström, M and Zeberg, H and Ollila, HM},
title = {Genome-wide association study of long COVID.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {40399555},
issn = {1546-1718},
abstract = {Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.},
}

@article {pmid40397934,
year = {2025},
author = {Khakban, I and Jain, S and Gallab, J and Dharmaraj, B and Zhou, F and Lokker, C and Abdelkader, W and Zeraatkar, D and Busse, JW},
title = {Impact of the COVID-19 Pandemic and the 2021 National Institute for Health and Care Excellence Guidelines on Public Perspectives Toward Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Thematic and Sentiment Analysis on Twitter (Rebranded as X).},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e65087},
doi = {10.2196/65087},
pmid = {40397934},
issn = {1438-8871},
mesh = {*COVID-19/epidemiology ; *Fatigue Syndrome, Chronic/therapy/psychology/diagnosis ; Humans ; *Social Media ; United Kingdom/epidemiology ; SARS-CoV-2 ; Pandemics ; Practice Guidelines as Topic ; *Public Opinion ; },
abstract = {BACKGROUND: Myalgic encephalomyelitis (ME), also referred to as chronic fatigue syndrome (CFS), is a complex illness that typically presents with disabling fatigue and cognitive and functional impairment. The etiology and management of ME/CFS remain contentious and patients often describe their experiences through social media.

OBJECTIVE: We explored public discourse on Twitter (rebranded as X) to understand the concerns and priorities of individuals living with ME/CFS, with a focus on (1) the COVID-19 pandemic and (2) publication of the 2021 UK National Institute for Health and Care Excellence (NICE) guidelines on the diagnosis and management of ME/CFS.

METHODS: We used the Twitter application programming interface to collect tweets related to ME/CFS posted between January 1, 2010, and January 30, 2024. Tweets were sorted into 3 chronological periods (pre-COVID-19 pandemic, post-COVID-19 pandemic, and post-UK 2021 NICE Guidelines publication). A Robustly Optimized Bidirectional Embedding Representations from Transformers Pretraining Approach (RoBERTa) language processing model was used to categorize the sentiment of tweets as positive, negative, or neutral. We identified tweets that mentioned COVID-19, the UK NICE guidelines, and key themes identified through latent Dirichlet allocation (ie, fibromyalgia, research, and treatment). We sampled 1000 random tweets from each theme to identify subthemes and representative quotes.

RESULTS: We retrieved 906,404 tweets, of which 427,824 (47.2%) were neutral, 369,371 (40.75%) were negative, and 109,209 (12.05%) were positive. Over time, both the proportion of negative and positive tweets increased, and the proportion of neutral tweets decreased (P<.001 for all changes). Tweets mentioning fibromyalgia acknowledged similarities with ME/CFS, stigmatization associated with both disorders, and lack of effective treatments. Treatment-related tweets often described frustration with ME/CFS labeled as mental illness, dismissal of concerns by health care providers, and the need to seek out "good physicians" who viewed ME/CFS as a physical disorder. Tweets on research typically praised studies of biomarkers and biomedical therapies, called for greater investment in biomedical research, and expressed frustration with studies suggesting a biopsychosocial etiology for ME/CFS or supporting management with psychotherapy or graduated activity. Tweets about the UK NICE guidelines expressed frustration with the 2007 version that recommended cognitive behavioral therapy and graded exercise therapy, and a prolonged campaign by advocacy organizations to influence subsequent versions. Tweets showed high acceptance of the 2021 UK NICE guidelines, which were seen to validate ME/CFS as a biomedical disease and recommended against graded exercise therapy. Tweets about COVID-19 often noted overlaps between post-COVID-19 condition and ME/CFS, including claims of a common biological pathway, and advised there was no cure for either condition.

CONCLUSIONS: Our findings suggest research is needed to inform how best to support patients' engagement with evidence-based care. Furthermore, while patient involvement with ME/CFS research is critical, unmanaged intellectual conflicts of interest may threaten the trustworthiness of research efforts.},
}

*COVID-19/epidemiology
*Fatigue Syndrome, Chronic/therapy/psychology/diagnosis
Humans
*Social Media
United Kingdom/epidemiology
SARS-CoV-2
Pandemics
Practice Guidelines as Topic
*Public Opinion

@article {pmid40395923,
year = {2025},
author = {Nagase, M and Takeshita, Y and Tomooka, K},
title = {Treatment Strategy for Long COVID Based on Traditional Chinese Medicine.},
journal = {Juntendo medical journal},
volume = {71},
number = {2},
pages = {102-105},
pmid = {40395923},
issn = {2759-7504},
abstract = {Post-acute COVID-19 conditions, commonly known as 'long COVID', occur in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection, typically 3 months from the onset of COVID-19 with symptoms, lasting for at least 2 months, that cannot be explained by any alternative diagnoses. Although most symptoms improve over time, some patients experience significant limitations in their social lives. Under such circumstances, complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. There are a wide variety of CAM interventions, such as traditional Japanese medicine (Kampo medicine) and traditional Chinese medicine (TCM). In this study, we compared three studies using Kampo medicine with those using TCM and concluded that Kampo medicine, which is often practiced in Japan due to its historical background, may have some limitations in managing the diverse symptoms of long COVID because the symptoms of long COVID vary widely. Therefore, we propose that medical examinations based on TCM should also be considered as an alternative treatment strategy for patients with long COVID.},
}

@article {pmid40393269,
year = {2025},
author = {Struhal, W and Almamoori, D},
title = {A review of the sequelae of post Covid-19 with neurological implications (post-viral syndrome).},
journal = {Journal of the neurological sciences},
volume = {474},
number = {},
pages = {123532},
doi = {10.1016/j.jns.2025.123532},
pmid = {40393269},
issn = {1878-5883},
abstract = {Post Covid-19 conditions represent a medical challenge; a unified definition is not achieved after 5 years of the Pandemic. The incidence of Post Covid-19 conditions varies, nevertheless the neurological complications represent an important aspect in the spectrums of fields involved. The current perception is that varied manifestations and long-term complications of COVID-19 reflect underlying pathophysiological processes, including inflammatory, immune-mediated, and vascular mechanisms. These mechanisms underscore the complexity of COVID-19's impact including the nervous system and its potential for lasting effects. A number of symptoms are extremely severe and may also need neurologic attention including fatigue, cognitive disturbances, autonomic symptoms, headache, and sleep disorders. Post Covid-19 conditions are often of chronic nature. Management as in other chronic conditions should rely on the conventional diagnostic measures and management of symptoms irrespective of the temporal relation to the viral infection. To date Post Covid-19 conditions is only accepted as an additional or explanatory diagnosis.},
}

@article {pmid40393061,
year = {2025},
author = {Junainah, EM and Abd-El-Rahman, AH and Alamin, AA and Hassan, KE and Elesawy, BH and Elrashidy, AH and Alhosary, AA and Tufail-Chaudhary, H and El-Kenawy, AE and Bashir, AF and Obaid-Alnefaie, G and Nemenqani, DM and El-Nashar, NA and Khairy, M and Al-Thobaiti, NA and Alfahmi, FK and Taha, SA},
title = {Immunopathology and therapeutic strategies for long COVID: mechanisms, manifestations, and clinical implications.},
journal = {AIDS reviews},
volume = {27},
number = {1},
pages = {25-32},
doi = {10.24875/AIDSRev.24000018},
pmid = {40393061},
issn = {1698-6997},
mesh = {Humans ; *COVID-19/immunology/complications/therapy ; Middle Aged ; Adult ; Male ; SARS-CoV-2 ; Longitudinal Studies ; Aged ; Female ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Adolescent ; Young Adult ; Autoantibodies/blood ; Inflammation/immunology ; Interleukin-6/blood ; },
abstract = {Long coronavirus disease-19 (COVID-19) is a complex, multifactorial condition characterized by persistent symptoms lasting more than 12 weeks following acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The underlying mechanisms remain incompletely understood, but chronic inflammation, immune dysregulation, autoimmunity, and viral persistence are increasingly being implicated. This study investigated the immunopathological drivers of long COVID-19 and their associations with clinical manifestations and organ damage. A prospective, longitudinal cohort study was conducted on 200 COVID-19 survivors aged 18-65 years, in which immune markers, autoantibody profiles, lymphocyte dysfunction, and imaging findings were assessed over a 12-month period. Persistent inflammation was observed, with elevated interleukin-6 and tumor necrosis factor α ± levels correlated with lung fibrosis and cognitive impairment. Autoantibodies were detected in 40% of the participants, particularly those with cardiovascular and neurological symptoms. A significant reduction in CD8+ T-cell counts was associated with severe fatigue and cognitive dysfunction, whereas persistent SARS-CoV-2 RNA was identified in 10% of cases, primarily in individuals with gastrointestinal symptoms. Imaging studies revealed multiorgan involvement, with structural abnormalities in the lungs, heart, and brain. These findings highlight the interplay of immune dysfunction, chronic inflammation, and autoimmunity in long-term COVID-19, underscoring the need for targeted therapeutic strategies to address its long-term health impacts.},
}

Humans
*COVID-19/immunology/complications/therapy
Middle Aged
Adult
Male
SARS-CoV-2
Longitudinal Studies
Aged
Female
Prospective Studies
Post-Acute COVID-19 Syndrome
Adolescent
Young Adult
Autoantibodies/blood
Inflammation/immunology
Interleukin-6/blood

@article {pmid40393039,
year = {2025},
author = {Carr, CR and Gentile, NL and Bertolli, J and Szewczyk, W and Lin, JS and Unger, ER and Vu, QM and Sotoodehnia, N and Fitzpatrick, AL},
title = {Comparison of long COVID, recovered COVID, and non-COVID Post-Acute Infection Syndromes over three years.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0323104},
pmid = {40393039},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/diagnosis/virology ; Female ; Male ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2/isolation & purification ; Adult ; Electronic Health Records ; },
abstract = {BACKGROUND: Comparing the characteristics of patients with long COVID to those with other post-acute infection syndromes (PAIS) could potentially provide clues to common underlying disease processes that may affect patient recovery.

METHODS: We identified records of patients who had documented SARS-CoV-2 tests in the University of Washington Medicine electronic health record (EHR) database from January 1, 2019, through January 31, 2022 (n = 139,472). Patients were classified into three groups: 1) long COVID defined by a positive SARS-CoV-2 test and a long COVID-related diagnosis code (n = 580); 2) recovered COVID defined by a positive test and no long COVID associated diagnosis codes (n = 7,437); and 3) non-COVID PAIS defined by a negative test, non-SARS-CoV-2 related PAIS diagnosis codes, and no COVID related codes (n = 106). Using multivariate logistic regression, we compared the clinical characteristics of these groups at three timeframes to address preclinical, acute and post-acute diagnoses: before index SARS-CoV-2 test, within 30 days of index test, and > 30 days after index test.

RESULTS: The long COVID group had a higher Charlson comorbidity index [median (IQR), 2 (0-4)] than the other two patient groups [median (IQR), 1 (0-3) and 1 (0-3)]. The long COVID and non-COVID PAIS patients were older and had greater smoking exposure than the recovered COVID group. Compared to the recovered COVID control group, the long COVID group had more health problems prior to the infection, including respiratory and metabolic as well as more severe infections and comorbidities based on the ICD codes found in the acute phase records. In the post-acute timeframe, many symptoms were more likely to be associated with long COVID than recovered patients with COVID-19 including abnormalities of heart beat [OR (95% CI), 5.31 (3.96-7.13)], cognition, perception, or emotional state symptoms [OR (95% CI), 5.14 (3.81-6.92)], malaise and fatigue [OR (95% CI), 4.20 (3.13-5.63)], and sleep disorders [OR (95% CI), 2.47, (1.79-3.43)], all p < 0.05. In contrast, the non-COVID PAIS group shared many similarities with the long COVID group across all three timeframes.

CONCLUSIONS: Patients diagnosed with long COVID were more similar to patients with a non-COVID-related PAIS than to recovered patients with COVID-19. This suggests risk factors for PAIS may be similar and independent of the infectious agent.},
}

Humans
*COVID-19/epidemiology/diagnosis/virology
Female
Male
Middle Aged
Post-Acute COVID-19 Syndrome
Aged
SARS-CoV-2/isolation & purification
Adult
Electronic Health Records

@article {pmid40392206,
year = {2025},
author = {Hery, CM and Zhang, X and McLaughlin, E and Von Ah, D and Anderson, GL and Harris, HR and VoPham, T and Garcia, L and Shadyab, AH and Follis, S and Paskett, ED},
title = {Association of Cancer History with COVID-19 Risk and Outcomes Among Older Postmenopausal Women: Results from the Women's Health Initiative.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1682},
pmid = {40392206},
issn = {1538-7755},
abstract = {BACKGROUND: Several studies early in the COVID-19 pandemic suggested those with a cancer history had higher risk of COVID-19 infections and complications. However, few prospective studies evaluated the association of cancer with COVID-19 in older women. We aimed to examine the association of cancer history with risk of COVID-19 and various COVID-19 outcomes among older women.

METHODS: The Women's Health Initiative (WHI) is an ongoing cohort study that recruited 161,808 postmenopausal women aged 50-79 from 1993-1998. Those who completed the COVID-19 survey (2021-2022) were included (n=35,623). Multivariable linear and logistic regression were used to examine COVID-19 positivity, symptoms severity, long COVID, and COVID concerns/anxiety outcomes.

RESULTS: 28% (n=9,901) of participants had a history of cancer. Cancer history was not significantly associated with COVID-19 positivity (OR: 0.94, 95% CI: 0.81-1.08), COVID-19 hospitalization (OR: 1.21, 95% CI: 0.85-1.72), number of symptoms (LS Mean: 0.33, 95% CI: -0.20, 0.85), and long COVID (OR: 1.18, 95% CI: 0.88-1.58).

CONCLUSIONS: History of cancer was not associated with most COVID-19 outcomes. Future studies should continue to examine physiological mechanisms contributing to differences within cancer survivors and prioritize the inclusion of underserved populations to identify strategies to address the impact of COVID-19.

IMPACT: These findings may assure cancer survivors their diagnosis alone does not increase their risk of COVID-19 and suggests older women with a history of cancer may have similar risk of COVID-19 outcomes compared to their non-cancer counterparts.},
}

@article {pmid40391677,
year = {2025},
author = {Silver, SR and Li, J and Saydah, SH},
title = {Burden of Selected Chronic Conditions Among Adults of Prime Working Age (25-54) by 2022 Self-Reported COVID-19 and Long COVID History Compared to 2019 Pre-Pandemic Baseline Prevalence: Behavioral Risk Factor Surveillance System.},
journal = {American journal of industrial medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajim.23735},
pmid = {40391677},
issn = {1097-0274},
support = {//The authors received no specific funding for this work./ ; },
abstract = {INTRODUCTION: Prior research has observed increased risks for numerous chronic conditions among individuals with Long COVID. Chronic conditions have been associated with employment limitations and increased economic hardships. Data from the Behavioral Risk Factor Surveillance System (BRFSS) present an opportunity to examine changes by employment status in the prevalence of a range of chronic conditions between 2019 (pre-pandemic) and, in 2022, by self-reported COVID-19 or Long COVID.

METHODS: We assessed the prevalence of chronic conditions in 2022 by employment status and self-reported COVID-19 and Long COVID history using data from BRFSS for adults of prime working age (25-54 years) who were employed for wages, self-employed, unemployed less than 1 year, unemployed 1 year or more, or unable to work. For each chronic condition (coronary heart disease and myocardial infarction [combined], stroke, ever and current asthma, chronic obstructive pulmonary disease, kidney disease, diabetes, and arthritis), we generated adjusted prevalence ratios (aPRs) comparing 2022 prevalence by COVID-19/Long COVID category to prevalences among respondents in that employment status before the pandemic (2019).

RESULTS: The prevalence of both asthma and diabetes increased significantly between 2019 and 2022 among respondents in all included employment categories and COVID-19/Long COVID histories combined. Among employed respondents with Long COVID in 2022, aPRs using 2019 prevalence figures for all employed respondents as a baseline for comparison had statistically significant elevations for every chronic condition assessed.

CONCLUSIONS: The increased prevalence of a range of chronic conditions between 2019 and 2022 among adults with Long COVID may present a burden for individuals, the workplace, the healthcare system, and the economy. Additional research in a longitudinal context could better quantify these associations. Efforts to prevent, identify, and treat Long COVID can reduce this burden.},
}

@article {pmid40391100,
year = {2025},
author = {Dassaye, R and Chetty, T and Daniels, B and Ramraj, T and Gaffoor, Z and Spooner, E and Mthethwa, N and Nsibande, DF and Magasana, V and Mohlabi, K and Singini, I and Gwebushe, N and Woeber, K and Goga, A},
title = {SARS-CoV-2 seroprevalence among learners in grades 1-7, their parents and teachers in KwaZulu-Natal, South Africa: a cross-sectional study.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1548945},
pmid = {40391100},
issn = {2296-2565},
mesh = {Humans ; South Africa/epidemiology ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Seroepidemiologic Studies ; Male ; Female ; *Parents ; *School Teachers/statistics & numerical data ; Child ; *SARS-CoV-2/immunology ; Adolescent ; Adult ; *Students/statistics & numerical data ; Schools ; Prevalence ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: There is limited information on SARS-CoV-2 seroprevalence among children and adolescents in LMIC school settings. We aimed to assess (1) the seroprevalence of SARS-CoV-2 antibodies, (2) prevalence of self-reported or confirmed SARS-CoV-2 prior infections and, (3) COVID-19 symptoms (including long-COVID) among a cohort of primary school learners, their parents and teachers in a semi-rural school setting approximately 3-years into the COVID-19 pandemic.

METHODS: Learners in grades 1-7 attending two pre-selected schools in close proximity in the Ndwedwe area, iLembe district, KwaZulu-Natal, South Africa, their parents and teachers were invited to enroll into the COVID Kids Schools Study (CoKiDSS) - a cross-sectional survey conducted between May-August 2023. All participants provided informed consent, completed a questionnaire and provided a fingerprick of blood for SARS-CoV-2 antibody testing using the COVID-19 IgG/IgM Rapid Test. Statistical methods included descriptive analysis, jackknife-estimated seroprevalence and incidence (unadjusted and sensitivity-adjusted), and logistic regression using generalized linear models.

RESULTS: A total of 645 participants (i.e., 456 learners, 147 parents and 42 teachers) were enrolled into the survey. Overall SARS-CoV-2 IgG seroprevalence was 78% unadjusted to 81% adjusted with an increasing seropositivity trend, from learners to teachers (76% unadjusted to 79% adjusted in learners, 79% unadjusted to 82% adjusted in parents and 93% unadjusted to 97% adjusted in teachers). About 2.6% of learners tested IgM seropositive. Interestingly, 17% of the participants, including 20% learners, tested negative for SARS-CoV-2 antibodies. While only 16 participants (2.5% - 2 learners, 10 parents, and four teachers) self-reported a prior confirmed SARS-CoV-2 infection. Of these 2 learners (100%), eight parents (80%) and 4 teachers (100%) reported COVID-19 like symptoms that persisted for ≥28-days.

CONCLUSION: We reported high SARS-CoV-2 IgG seroprevalence among learners in grades 1-7, their parents and teacher approximately 3 years into the COVID-19 pandemic which may be attributed to the snowball effect of multiple waves of infection in South Africa. However, only a small proportion of participants self-reported prior COVID-19 infection. This may be due to (1) recall bias and participants' perception of low susceptibility to and severity of COVID-19, (2) limited access to SARS-CoV-2 testing, and/or (3) a high prevalence of asymptomatic infections.},
}

Humans
South Africa/epidemiology
Cross-Sectional Studies
*COVID-19/epidemiology
Seroepidemiologic Studies
Male
Female
*Parents
*School Teachers/statistics & numerical data
Child
*SARS-CoV-2/immunology
Adolescent
Adult
*Students/statistics & numerical data
Schools
Prevalence
Surveys and Questionnaires

@article {pmid40391044,
year = {2025},
author = {Duenas, K and Chwa, WJ and Hoque, F},
title = {Overview of Long COVID: Navigating the Aftermath.},
journal = {Journal of Brown hospital medicine},
volume = {4},
number = {2},
pages = {133879},
pmid = {40391044},
issn = {2994-5593},
abstract = {The coronavirus disease (COVID-19) pandemic was a global health crisis with far-reaching consequences. Among these were physical and mental health complications that emerged weeks or even months after the initial COVID-19 infection, collectively termed "long COVID" or "post-COVID syndrome." Identifying the epidemiology, risk factors, clinical manifestations, and management strategies for long COVID is crucial for both clinicians and patients, which is the focus of this review. The prevalence of long COVID varies across studies, generally ranging from 5% to 20%. Prominent risk factors include female sex, older age, a high number of acute symptoms, lower socioeconomic status, and underlying comorbidities such as diabetes, asthma, or chronic obstructive pulmonary disease. The clinical manifestations of long COVID are diverse; beyond the commonly reported symptoms of fatigue, malaise, ageusia, and anosmia, neuropsychiatric complications such as headache, cognitive deficits, and depression are also potential outcomes. Although there is currently no consensus on the management of long COVID, multidisciplinary care teams with appropriate referrals and follow-up diagnostic studies are essential in evaluating the clinical course of long COVID patients.},
}

@article {pmid40390477,
year = {2025},
author = {Finsterer, J},
title = {The Spectrum of Long-COVID Symptoms Should Be Assessed Through On-Site Examinations Rather Than Electronic Questionnaires.},
journal = {The American journal of medicine},
volume = {138},
number = {6},
pages = {e119},
doi = {10.1016/j.amjmed.2024.06.017},
pmid = {40390477},
issn = {1555-7162},
}

@article {pmid40390475,
year = {2025},
author = {Finsterer, J},
title = {If Internal Tremor and Vibrations in Long-COVID Cannot Be Confirmed by Abnormal Instrumental Examinations, Psychiatrists are Required.},
journal = {The American journal of medicine},
volume = {138},
number = {6},
pages = {e117},
doi = {10.1016/j.amjmed.2024.07.032},
pmid = {40390475},
issn = {1555-7162},
}

@article {pmid40389117,
year = {2025},
author = {Rudroff, T},
title = {Climate crossroads: How global warming drives coronavirus emergence, the long COVID crisis of tomorrow, and AI's role in navigating our future.},
journal = {Infectious diseases now},
volume = {55},
number = {6},
pages = {105091},
doi = {10.1016/j.idnow.2025.105091},
pmid = {40389117},
issn = {2666-9919},
abstract = {This narrative review examines the critical nexus between climate change, coronavirus emergence, and Long COVID-a triad that may shape public health outcomes for generations. Climate change disrupts ecological balances that have historically limited viral spillover events, creating novel interfaces between wildlife reservoirs and human populations. The coronavirus family presents particular concern due to its diversity, adaptability, and demonstrated capacity for cross-species transmission. With over 200 coronaviruses identified in bat populations alone, this vast reservoir of genetic diversity, combined with the family's propensity for recombination, creates substantial pandemic potential that climate disruption may further amplify. Long COVID has revealed another dimension of the coronavirus threat: the potential for significant chronic disease burden following acute infection. This complex multisystem condition affects a substantial portion of SARS-CoV-2 infected individuals, with mechanisms including viral persistence, autoimmunity, microclot formation, and mitochondrial dysfunction. Future projections suggest that climate change could increase global viral spillover risk by 30-45% by 2070, particularly in Southeast Asia, Central Africa, and parts of South America. Artificial intelligence offers promising tools for addressing these interconnected challenges through enhanced surveillance, accelerated therapeutic development, and optimized healthcare delivery. Understanding the climate-coronavirus-chronic illness nexus has become essential to the development of resilient health systems and effective planetary health policies face to an uncertain future.},
}