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Bibliography on: Long Covid

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 30 Oct 2025 at 01:52 Created: 

Long Covid

Wikipedia: Long Covid refers to a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. Long COVID is characterised by a large number of symptoms, which sometimes disappear and reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. Many other symptoms can also be present, including headaches, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction and problems with mental health. Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. Diagnosis of long COVID is based on suspected or confirmed COVID-19 infection, symptoms and by excluding alternative diagnoses. Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. Prevalence is less after vaccination.

Created with PubMed® Query: ( "long covid" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2025-10-29
CmpDate: 2025-10-29

Vishnu P, DM Aboulafia (2025)

Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.

Clinics in laboratory medicine, 45(4):643-655.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Ozawa T, Terai H, Tanaka H, et al (2025)

Japanese nationwide survey to track the impact of long COVID over 3 years.

Environmental health and preventive medicine, 30:84.

BACKGROUND: The long-term impact of symptom classification on quality of life (QOL) and economic outcomes among individuals with long coronavirus disease (COVID) remains poorly understood. This study aimed to clarify the situation of long COVID in Japan by analyzing patients using cluster classification.

METHODS: This multicenter, retrospective cohort study enrolled 515 patients with COVID-19 and followed up for 36 months via standardized questionnaires. Patients were classified based on: 1) symptom trajectory over time and 2) symptom cluster profiles at 3 months.

RESULTS: While the number of symptoms decreased, fatigue and dyspnea frequently persisted, whereas anosmia and dysgeusia declined. Cough and sputum decreased gradually. The proportion of patients with 5-9 symptoms increased. The mean (interquartile range) presenteeism scores were lower in the continuous (60 [50-80]) and relapse groups (65 [48-80]) than in the recovered group (70 [50-80]). The multiple symptoms cluster had the worst SF-36, presenteeism, and absenteeism scores (47.2 [44.7-49.8], 48.8 [27.5-72.5], and 10.9 [0.0-11.0], respectively).

CONCLUSIONS: Patients with continuous and multiple symptoms experienced persistently lower QOL and greater economic burden up to 36 months after COVID-19 diagnosis. The long-term effects of long COVID are not only physical but also mental and economical. Thus, further research is needed to clarify the economical and physiological impact of long COVID.

RevDate: 2025-10-29

Krassnig K, Bauer R, Glasl S, et al (2025)

[Herbal treatment options for post-viral symptoms and long COVID].

Wiener medizinische Wochenschrift (1946) [Epub ahead of print].

BACKGROUND: Long COVID and post-viral symptom complexes have become a significant focus in medical practice. There is an urgent need to provide evidence-based treatment options to those patients. The aim of the literature review was to summarize herbal medicinal products as a treatment option for post-viral conditions, particularly long COVID.

METHODS: A working group of the Austrian Society for Phytotherapy conducted a narrative review between 2022 and 2024, based on external literature from the PubMed, PubPharm and Scopus databases and clinical experience from practice. The review identified the most relevant medicinal plants and their preparations for the most common symptom complexes of long COVID.

RESULTS: A total of 98 publications and 24 monographs were included in the literature review. The symptom complexes (+ relevant phytopharmaceuticals) include neurological complaints, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Ginseng radix, Panax quinquefolii radix, Eleutherocci radix, Rhodiolae rhizoma et radix, Schisandrae fructus), nootropics (Ginkgo folium, Lavandulae flos), irritations of the respiratory tract (Liquiritiae radix, Nigellae semen, Eucalypti folium), gastrointestinal complaints (Gentianae radix, Centauri herba, Artemisii herba, Galangae rhizoma, Zingiberis rhizoma, Boswellia serrata, Curcuma longae rhizoma), circulatory weakness (Crataegi folium cum flore, Rosmarini folium, Salviae officinalis folium) and loss of smell (Rosae flos, Citri pericarpium, Caryophylli flos, Eucalypti folium). External evidence and clinical experience in medical practice show that many important symptoms of post-viral conditions can be successfully treated with herbal preparations.

CONCLUSION: Phytopharmaceuticals can provide evidence-based support for the therapeutic portfolio for viral diseases and their consequences in current and future viral epidemics.

RevDate: 2025-10-29

Dette A, Moers F, Mayr T, et al (2025)

Differential expression of viral entry protein neuropilin 1 (NRP1) and neuropilin 2 (NRP2) in fatal COVID-19.

Journal of virology [Epub ahead of print].

Coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, endothelialitis, hypoxemia, and hypercoagulation, contributing to thrombosis in acute severe and long COVID. While ACE2 is the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, its low expression in certain infected cell types suggests alternative co-receptors. Neuropilins (NRP1 and NRP2), widely expressed, have been proposed as co-factors for viral entry. We analyzed NRP1 and NRP2 expression in autopsy tissues from heart, lung, and hematolymphoid organs using immunohistochemistry (n = 20) and compared findings with public single-cell RNA sequencing (scRNAseq) data. Selected cases were further examined by spatial multiplex immunofluorescence (CODEX). In vitro binding of NRP1/NRP2 to SARS-CoV-2 spike fragments S1 and S1' was assessed by immunofluorescence microscopy. NRP1 was abundantly expressed in myocardial capillary endothelial cells (ECs) and macrophages in the heart and lung; NRP2 was found in alveolar macrophages and mast cells. scRNAseq re-analysis confirmed these in situ patterns. In vitro, NRP1 exclusively bound S1, while NRP2 bound both S1 and S1'. SARS-CoV-2 RNA was detected in neuropilin-positive, ACE2/TMPRSS2-negative vascular EC and mast cells. The detection of SARS-CoV-2 RNA in neuropilin-positive but ACE2/TMPRSS2-negative cell clusters supports that neuropilins are involved in systemic viral dissemination. NRP1 on vascular EC may contribute to angiogenesis, vascular damage, and microangiopathy, while NRP2 represents a potential immunomodulatory target to regulate macrophage activity, resolve inflammation, and potentially prevent the progression of pulmonary fibrosis and limit excessive mast cell activation in long COVID.IMPORTANCEThe well-known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), exhibits low expression in key cell types implicated in coronavirus disease 2019 (COVID-19) pathology, such as endothelial cells and B cells, macrophages, and mast cells. In contrast, neuropilins, identified as co-receptors for SARS-CoV-2, are abundantly expressed in these cells under physiological conditions and may be involved in virus-host interactions. This study presents a detailed in situ analysis of Neuropilin 1 (NRP1) and Neuropilin 2 (NRP2) expression in fatal COVID-19 cases using immunohistochemistry and spatial multiplex immunofluorescence phenotyping, complemented by single cell RNA sequencing. Additionally, it demonstrates differential binding affinities of NRP1 and NRP2 to SARS-CoV-2 spike protein fragments S1 and S1' in vitro, suggesting distinct roles for these neuropilins in viral recognition. This study highlights the impact of the unique furin cleavage site in SARS-CoV-2, which may contribute to increased pathogenicity through its interaction with NRP1.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Guzmán V, Di Gravio C, Cooper E, et al (2025)

"I Put a Lot of Emphasis on Work Because I Want to Keep My Job": A Population-Based Interview Study of Long Covid and Employment Changes in England.

Health expectations : an international journal of public participation in health care and health policy, 28(6):e70476.

BACKGROUND: Long Covid is a complex condition characterised by persistent multisystemic symptoms following a Covid-19 infection, which can influence an individual's capability to sustain employment. However, there is limited evidence of how diverse presentations of long Covid can shape employment and what support strategies might be useful for different groups.

AIM: To address this, we aimed to explore the experiences of employment changes among people living with long Covid in England and to identify the perceived barriers and enablers they face to cope with work.

DESIGN AND METHODS: We conducted a qualitative analysis of data from the Real-time Assessment of Community Transmission (REACT) Study. Using a framework analysis approach, we analysed 60 semi-structured interviews with people who experienced persistent Covid-19 symptoms for 12 weeks or more.

RESULTS: We identified three key themes: (1) Persistent Covid-19 symptoms at work; (2) Ripple effects of balancing work, identity and well-being with persistent Covid-19 symptoms; and (3) Employment changes to cope with and manage persistent Covid-19 symptoms. Participants identified multiple employment changes, including reduction of working hours, restructuring of roles and modification of responsibilities, and adapted ways of working. Drivers of employment changes included disruptive and fluctuating symptoms but also broader pandemic circumstances and the opportunities available for accessing organizational support and putting in place appropriate management strategies.

CONCLUSION: Our results provide a thorough understanding of the work changes experienced by people living with long Covid and highlight the need for intersectional, adaptable work accommodations to support their sustainable employment and overall well-being.

Members of the public who are part of a Public Advisory Group (PAG) have provided ongoing input into various aspects of the umbrella cohort study, the Real-time Assessment of Community Transmission (REACT) Study, including the study design, data collection instruments and dissemination of findings. For this qualitative study, which draws on interview data from REACT Long COVID (REACT-LC), preliminary findings were presented to the PAG for feedback and suggestions, which helped refine the discussion. Additionally, two Public Advisors with lived experience of long Covid contributed to the writing and editing of this manuscript. In accordance with these contributions, they are included as authors.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Huff HV, Villanueva-Colina C, Diaz MM, et al (2025)

Correction: Neurologic symptoms following COVID-19 in Lima, Peru: a prospective longitudinal observational study.

Frontiers in neurology, 16:1676667.

[This corrects the article DOI: 10.3389/fneur.2025.1524613.].

RevDate: 2025-10-29
CmpDate: 2025-10-29

Xie K, Zhang P, Li Y, et al (2025)

The post-COVID-19 pulmonary sequelae: manifestations, mechanisms and treatment strategies.

Journal of thoracic disease, 17(9):7414-7429.

Recent studies have increasingly demonstrated that coronavirus disease 2019 (COVID-19) patients may develop long-term sequelae of varying severity, collectively referred to as long COVID or post-COVID-19 condition. Pulmonary sequelae are particularly common, which significantly impair patients' quality of life. The mechanisms underlying post-COVID-19 pulmonary sequelae are complex and multifactorial, and their management is still at an exploratory stage. This review explores the manifestations, underlying mechanisms, and potential treatment approaches for post-COVID-19 pulmonary sequelae. Fatigue, dyspnea, myalgia, and sleep disturbances are the most commonly reported symptoms following COVID-19 infection, while anxiety and depression are also prevalent. Respiratory symptoms include dyspnoea, persistent cough, hypoxia, and reduced exercise capacity. Impaired lung diffusion capacity is the most frequently observed pulmonary function abnormality, and residual abnormalities on chest computed tomography (CT) commonly include ground-glass opacities (GGO) and fibrotic-like changes. Air trapping is also an important CT finding and has been reported to associated with impaired lung diffusion function. The potential mechanisms may include pulmonary fibrosis, chronic inflammation, immune dysregulation, coagulation abnormalities and thrombosis, and persistent viral infection. Current treatment strategies encompass vaccination, pulmonary rehabilitation, and pharmacological interventions such as antifibrotic, anti-inflammatory, and anticoagulant therapies. A comprehensive understanding of the recovery trajectory and the mechanisms underlying post-COVID-19 pulmonary sequelae is crucial for improving patient outcomes.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Matyja-Bednarczyk A, Dziedzic R, Drynda A, et al (2025)

Baseline Dysregulation in B, T, and NK Cells in COVID-19 Predicts Increased Late Mortality but Not Long-COVID Symptoms: Results from a Single-Center Observational Study.

Viruses, 17(10): pii:v17101400.

The SARS-CoV-2 pandemic presents a broad clinical spectrum from asymptomatic cases to severe respiratory failure with high mortality. Severe COVID-19 is characterized by immune dysregulation, including lymphopenia and alterations in the counts of T, B, and NK cells in peripheral blood. Due to the limited data on long-term outcomes related to immune dysregulation, we aimed to analyze immunologic features at baseline in severe and mild COVID-19 cases and assess follow-up characteristics associated with later mortality and long-COVID signs. We included adult patients consecutively hospitalized with COVID-19 between June and November 2020 at the University Hospital in Kraków, corresponding to the first and second waves of COVID-19 in Poland. We enrolled only those who had been thoroughly assessed in terms of clinic and laboratory data, including immunological workups, and survived the acute phase of the disease. In 2025, between February and April (median time of follow-up: 54 months), we conducted a telephone questionnaire on long-COVID symptoms among survivors who had given their consent. Statistical analyses were performed to compare groups with severe and mild disease in terms of dysregulation in lymphocyte subpopulations and the follow-up outcomes. The study included 103 COVID-19 patients, comprising 53 severe (based on the need for at least high-flow nasal oxygen therapy) and 50 mild cases, with no differences in age, sex, and body mass index. Severe COVID-19 patients compared to mild cases had lower CD3+ T cells (count and percentage), CD4+ T cells (count and percentage), CD8+ T cells (count), and NK cells (count), but higher CD19+ B cells (percentage) at baseline (p < 0.05, all). At the time of follow-up, we evaluated 80 patients (77.7% of the baseline participants), with 23 (22.3%) patients lost to follow-up. Among patients analyzed in the follow-up, 23 (28.8%) had died, and 29 of the 57 survivors (50.9%) reported persistent long-COVID symptoms. Patients who died had significantly lower baseline counts of CD3+ T cells (377 vs. 655 cells/µL), CD4+ T cells (224 vs. 372 cells/µL), CD8+ T cells (113 vs. 188 cells/µL), and NK cells (118 vs. 157 cells/µL) compared to survivors (p < 0.05, all). Notably, the percentage of CD19+ B cells was higher in deceased individuals (19.2% vs. 13.5%; p = 0.049). In contrast, we did not document differences in baseline immunological data among survivors with and without long-COVID signs. Our study suggests that dysregulation in lymphocyte subpopulations during the COVID-19 acute phase may be associated with increased late mortality, but not with the persistence of long-COVID symptoms.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Heath AM, D Li (2025)

Symptomatology of Long COVID Associated with Inherited and Acquired Thrombophilic Conditions: A Systematic Review.

Viruses, 17(10): pii:v17101315.

Thrombophilic conditions, conditions where blood has a tendency to form thrombi due to abnormal coagulatory processes, can affect the trajectory of diseases such as Post-Acute Sequelae of SARS-CoV-2 Infection, better known as Long COVID (LC), by worsening symptoms and complicating outlooks. As a comorbidity in pro-coagulatory diseases such as COVID-19 and LC, patients with thrombophilic conditions may experience worse symptoms than their peers, due to this elevated level of hypercoagulation. A 15-week literature review through the public PubMed database was conducted to investigate the severity, mechanisms, and symptom profiles of thrombophilic patients with LC. Papers were only included if samples included participants with pre-existing tendencies for hypercoagulable states, and confirmation of SARS-CoV-2 infection via a Polymerase Chain Reaction test. Each paper included in this review was analyzed by topic and assessed for eligibility against the Joanna Briggs Institute's Critical Appraisal tool. Each paper was also assessed for biases. Results from the 6 papers included in this review showed that LC could be predicted following COVID-19 illness by a hypercoagulable blood profile, indicating that LC may be linked to chronic hypercoagulation and inflammation post-infection. Additionally, symptoms linked to microthrombi formation, such as hair loss, arrhythmia, and dizziness, were exhibited more frequently in patients with thrombophilia and/or thrombophilic conditions, indicating that those with thrombophilic conditions may exhibit unique LC symptom profiles compared to healthy controls. This paper's research is preliminary and thus is limited in the strength of its findings; However, further research into LC and its interactions with co-morbidities like thrombophilic conditions would aid in the development of better treatment plans for patients, such as the usage of anticoagulants or screening for hypercoagulable blood profiles post-COVID-19 to assess patient risk.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Prakash S, Karan S, Lekbach Y, et al (2025)

Insights into Persistent SARS-CoV-2 Reservoirs in Chronic Long COVID.

Viruses, 17(10): pii:v17101310.

Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments ("brain fog"), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4[+] and CD8[+] T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Lepojević-Stefanović D, Živković S, Marković D, et al (2025)

COVID-19 and Cardiovascular Complications: A Follow-Up Study from Tertiary Center.

Viruses, 17(10): pii:v17101293.

(1) Background: In addition to its fatal outcomes, COVID-19 is associated with a spectrum of non-fatal complications that significantly influence clinical trajectories and quality of life. Cardiovascular complications, in particular, are of major clinical relevance and are recognized as key contributors to both short- and long-term morbidity and mortality. The aim of the present study was to evaluate the short-term and long-term effects of COVID-19 infection on patients with underlying cardiovascular diseases. (2) Methods: The prospective cohort study included a total of 99 consecutive subjects hospitalized due to moderate and severe forms of COVID-19 pneumonia in "Zvezdara"-University Medical Center in the period of 18 March-18 April 2021. (3) Results: During hospitalization, 47% of patients had some new cardiovascular events. A total of 10 patients died during hospital stay. The highest chance for the lethal outcome was seen in those with previously diagnosed coronary heart disease (B = 3.356, OR = 28.667 (95% CI 2.69-305.14), p = 0.005), heart failure (B = 3.056, OR = 21.250 (95% CI 3.36-134.56), p = 0.001) and increased potassium values (B = 2.639, OR = 14.000 (95% CI 2.65-73.88), p = 0.002). (4) Conclusions: Care strategies for patients who survived the acute episode of COVID-19 should include attention to cardiovascular disease. Our findings emphasize the need for continued optimization of strategies for primary prevention of SARS-CoV-2 infections as the best way to prevent long COVID and serious cardiovascular complications.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Genova S, Pencheva M, Burnusuzov H, et al (2025)

High Free IgE and Mast Cell Activation in Long COVID: Mechanisms of Persistent Immune Dysregulation.

Life (Basel, Switzerland), 15(10): pii:life15101538.

Background: Elevated serum IgE has been reported in severe COVID-19, suggesting that mast cell activation, allergic-like responses, and possible viral immune evasion occur. Objective: This study aimed to assess serum IgE, IgG, eosinophils, basophils, IL-10, and IL-33 in COVID-19 patients, and evaluate the infiltration of mast cells, basophils, and plasma cells in fatal cases. Methods: This retrospective study included 21 patients with severe COVID-19 or related respiratory conditions hospitalized in Plovdiv, Bulgaria (February 2020-May 2022). Serum immunoglobulins were quantified via immunoassays; IL-10 and IL-33 were also measured. Lung tissues from 30 autopsies were examined histologically and immunohistochemically using CD117 (mast cells) and CD138 (plasma cells). Results: Elevated IgE (>100 IU/mL) occurred in 10/21 patients, with two patients exhibiting levels exceeding 1000 IU/mL. High IgE correlated with reduced eosinophils and basophils, except in post-COVID lobar pneumonia. IL-10 was significantly increased, while IL-33 was reduced in acute and long COVID. Lung histology showed the accumulation of mast cells and plasma cells (5-20/field) during the diffuse alveolar damage and acute respiratory distress syndrome (ARDS) phases, but not in later fibrotic stages. Basophils are located near capillary basement membranes and the endothelium. Conclusions: SARS-CoV-2 may induce IgE-driven allergic-like mechanisms that contribute to severity. Monitoring IgE and mast cell activity may provide prognostic and therapeutic value, while elevated IgG4 could mitigate the effects of IgE.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Jach ME, Sajnaga E, Bumbul M, et al (2025)

The Role of Probiotics and Their Postbiotic Metabolites in Post-COVID-19 Syndrome.

Molecules (Basel, Switzerland), 30(20): pii:molecules30204130.

Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut-brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Delpino MV, J Quarleri (2025)

Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.

Pathogens (Basel, Switzerland), 14(10): pii:pathogens14101045.

We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms-including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming-contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Robinson KF, Ahiya AI, Richner JM, et al (2025)

SARS-CoV-2 Infection Influences Wnt/β-Catenin Pathway Components in Astrocytes.

Pathogens (Basel, Switzerland), 14(10): pii:pathogens14100994.

The mechanisms by which SARS-CoV-2 infection lead to neuroinflammation and cognitive impairment in COVID-19 and Long COVID are unclear. Cerebrovascular Wnt/β-catenin pathway activity is suppressed in association with neuroinflammation and cognitive impairment in a mouse model of COVID-19. In this study, we asked whether SARS-CoV-2 (NY Iota strain) infection of astrocytes would result in cell-autonomous changes in Wnt/β-catenin pathway components. We report that induced pluripotent stem cell (hiPSC)-derived human astrocytes (iAs) are susceptible to sustained infection with SARS-CoV-2 in vitro. Real-time PCR revealed that SARS-CoV-2 infection of iAs decreased transcripts for Wnt3a, Wnt10b, and the downstream pathway effectors β-catenin and TCF3. Wnt7b was increased, as was the proinflammatory chemokine CXCL10. No changes were noted in Wnt3, Wnt7a, TCF1, TCF4, or LEF1. These data indicate that SARS-CoV-2 infection differentially influences Wnt/β-catenin pathway components in astrocytes. These data could have implications for the mechanistic basis of COVID-19 and Long COVID.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Navarro-Cáceres A, Gómez-Sánchez L, Arroyo-Romero S, et al (2025)

Relationship of Mediterranean Diet and Its Components with Parameters of Structure, Vascular Function, and Vascular Aging in Subjects Diagnosed with Long COVID: BioICOPER Study.

Nutrients, 17(20): pii:nu17203226.

INTRODUCTION: Long COVID (LC) is associated with an increase in cardiovascular risk and chronic inflammation, whereas the Mediterranean Diet (MD) seems to improve the aforementioned factors. The aim of this study is to analyse the relationship between MD and its components with vascular structure, function, and aging in patients diagnosed with LC globally and by sex.

METHODS: This study was a cross-sectional study with 304 subjects diagnosed with LC; 207 were women and 97 men. Adherence to MD was evaluated with a validated MEDAS questionnaire, composed of 14 items. The vascular structure was assessed using carotid intima-media thickness (cIMT). Three measurements were carried out to evaluate vascular function: cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), and carotid-femoral pulse wave velocity (cfPWV). Vascular aging index (VAI) was estimated.

RESULTS: The MD score was 7.80 ± 2.33, with no difference between sexes. Vascular function and aging parameter values were higher in men than in women. Use of olive oil as the principal source of fat for cooking, and consuming <1 serving of butter/day and <1 sugar-sweetened beverage/day showed >90% adherence. Logistic regression analysis displayed associations between cIMT < 0.625 and use of olive oil in the global analysis (OR = 0.148) and among men (OR = 0.120), and <2 commercial pastries/week in global (OR = 0.536). cfPWV < 7.400 m/s was associated with DM score ≥ 8 in global (OR = 0.444) and in women, as well as with <2 pastries/week in women (OR = 0.405). baPWV < 12.315 m/s was associated with ≥3 servings of pulses/week in global (OR = 0.481) and among women, as was <2 pastries/week in global (OR = 0.471) and in women. CAVI < 7.450 was associated with ≥4 tablespoons of olive oil/day in men. VAI < 63.693 was associated with DM score ≥ 8 in global (OR = 0.458) and in women, as well as <2 pastries/week in global (OR = 0.392).

CONCLUSIONS: Adherence to MD was associated with lower cfPWV and VAI measures in the global analysis and among women. In particular, several of the components were associated with a better vascular profile in LC patients.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Mîțu DA, Buleu F, Popa DI, et al (2025)

Outcomes, Sequelae, and Ventilatory Strategies in Long COVID Patients with Severe ARDS: A Retrospective Cohort Study.

Journal of clinical medicine, 14(20): pii:jcm14207223.

Background and Aims: Severe acute respiratory distress syndrome (ARDS) in patients with long COVID remains associated with extremely high mortality and significant long-term sequelae. Non-invasive ventilatory strategies such as continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC) are widely used before endotracheal intubation (ETI). Still, their comparative effectiveness in this population is not well established. Understanding survival outcomes and sequelae can help refine treatment strategies for this high-risk group. This study aimed to evaluate outcomes, sequelae, and treatment strategies in long COVID patients with severe ARDS, focusing on non-invasive ventilatory support before ETI. Materials and Methods: A retrospective cohort analysis was performed using a study comparing severe ARDS patients with and without COVID-19. The inclusion criterion was a Horovitz quotient (PaO2/FiO2) < 50 mmHg. Results: The study included a total of 59 patients diagnosed with long COVID-19 ARDS, with a mortality rate of 85%. A significant proportion of the patient population was male, accounting for 75%. The highest survival rate was observed among patients who initially received CPAP support, with a survival rate of 23.08%, in contrast to those treated solely with HFNC or those who alternated between HFNC and CPAP. Among patients who required endotracheal intubation and subsequent mechanical ventilation, survival rates were 40% for those who had previously received CPAP, 10% for those treated with alternating HFNC and CPAP, and 0% for those managed exclusively with HFNC before ETI. Survivors often exhibited sequelae, such as impaired pulmonary function, persistent dyspnea, and diminished physical performance. Conclusions: Patients with long COVID who develop severe ARDS (PaO2/FiO2 < 50 mmHg) face exceptionally high ICU mortality, with outcomes determined mainly by age, comorbidities, and profound hypoxemia. Although CPAP showed a trend toward improved survival, the data do not establish superiority and should be regarded as hypothesis-generating. Rather, they highlight the complexity of managing this underrepresented subgroup and underscore the need for larger, multicenter studies with broader inclusion criteria to confirm or refute these preliminary observations.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Caliman-Sturdza OA, Hamamah S, Iatcu OC, et al (2025)

Microbiome and Long COVID-19: Current Evidence and Insights.

International journal of molecular sciences, 26(20): pii:ijms262010120.

Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Mikheeva EV, Aulova KS, Nevinsky GA, et al (2025)

In Silico Analysis of MiRNA Regulatory Networks to Identify Potential Biomarkers for the Clinical Course of Viral Infections.

International journal of molecular sciences, 26(20): pii:ijms262010100.

MiRNA expression profiles exhibit notable alterations in numerous diseases, particularly viral infections. Consequently, miRNAs may be regarded as both therapeutic targets and markers for the development of complications. MiRNAs can significantly influence the modulation of immune responses, offering an extra layer of regulation during viral infections. In this study, miRNAs associated with viral infections were analyzed using an in silico approach. Computer modeling predicted a number of miRNAs capable of influencing the functionality of specific components of the immune system. As a result, 242 miRNAs common to the three types of infections were identified. A network of miRNA-gene regulatory interactions, encompassing 502 nodes (224 miRNAs and 278 genes) and 2236 interactions, was developed. Within this network, subnetworks were identified that are involved in the operation of specific connections in the immune response to viruses. For each step of the immune response, the miRNAs involved in governing these processes were examined. These predicted miRNAs are of particular interest for further analysis aimed at establishing the relationship between their differential expression and disease symptom severity. The obtained data lay the foundation for identifying the most promising molecules as predictive biomarkers and the subsequent development of a diagnostic system.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Refrigeri M, Tola A, Mogavero R, et al (2025)

Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.

International journal of molecular sciences, 26(20): pii:ijms26209885.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus-host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology.

RevDate: 2025-10-29
CmpDate: 2025-10-29

Wilson A, Ricciardiello Mejia GC, Lomba S, et al (2025)

A Multidimensional Assessment of Sleep Disorders in Long COVID Using the Alliance Sleep Questionnaire.

Healthcare (Basel, Switzerland), 13(20): pii:healthcare13202611.

Background/Objectives: Sleep disturbances are recognized as a common feature of Long COVID but detailed investigation into the specific nature of these sleep symptoms remain limited. This study analyzes comprehensive sleep questionnaire data from a Long COVID clinic to better characterize the nature and prevalence of sleep complaints in this population. Methods: We conducted a cross-sectional analysis of 200 adults referred to the Stanford Long COVID Clinic. Patients completed an intake questionnaire including three sleep-related items (unrefreshing sleep, insomnia, daytime sleepiness) rated on a 0-5 Likert scale. Additionally, patients completed the Alliance Sleep Questionnaire (ASQ), incorporating the Insomnia Severity Index, Epworth Sleepiness Scale, reduced Morningness-Eveningness Questionnaire, and modules for parasomnia, restless legs, and breathing symptoms. We calculated the prevalence of six sleep symptom domains. Standardized symptom data were analyzed using principal component analysis (PCA) and K-means clustering (k = 2) to explore latent phenotypes and used logistic regression to assess associations between demographic and clinical variables and each sleep complaint. Results: Sleep-related breathing complaints affected 57.5% of participants, insomnia 42.5%, and excessive daytime sleepiness 28.5%. Parallel analysis supported a nine-factor structure explaining ~90% of variance, with varimax rotation yielding interpretable domains such as insomnia/unrefreshing sleep, fatigue/post-exertional malaise, parasomnias, and respiratory symptoms. Gaussian mixture modeling favored a two-cluster solution (n = 94 and n = 106); one cluster represented a higher-burden phenotype characterized by greater BMI, insomnia, daytime sleepiness, gastrointestinal symptoms, and parasomnias. Logistic models using factor scores predicted insomnia with high accuracy (AUC = 0.90), EDS moderately well (AUC = 0.81), but extreme chronotype poorly (AUC = 0.39). In adjusted models, hospitalization during acute COVID-19 was significantly associated with insomnia (OR 4.41; 95% CI 1.27-15.36). Participants identifying as multiracial had higher odds of insomnia (OR 3.22; 95% CI 1.00-10.34), though this narrowly missed statistical significance. No other predictors were significant. Conclusions: Sleep disturbances are frequent and diverse in Long COVID. Factor analysis showed overlapping domains, while clustering identified a higher-burden phenotype marked by more severe sleep and systemic complaints. Symptom-based screening may help target those at greatest risk.

RevDate: 2025-10-28

Raijmakers RPH, Lund Berven L, Keijmel SP, et al (2025)

Immunological associations in post-infective fatigue syndromes including Long COVID-a systematic review and meta-analysis.

EBioMedicine, 121:105970 pii:S2352-3964(25)00414-1 [Epub ahead of print].

BACKGROUND: The pathophysiology of post-infective fatigue syndromes (PIFS), including Long COVID, is unknown. This systematic review and meta-analysis aimed to investigate if PIFS is associated with persistent immune activation.

METHODS: PubMed, EMBASE, and Web of Science were searched for terms related to infection, fatigue, persistent symptoms, and immunological markers.

POPULATION: adults and adolescents; Exposure: documented acute infection; Comparator: those who developed PIFS vs. recovered controls from the same exposure; and Outcomes: immunological biomarkers. Studies which documented acute infection, applied diagnostic criteria for PIFS, and assayed circulating immunologic markers were eligible.

FINDINGS: From 14,985 studies screened, 30 articles were included (n = 5102 participants; 833 PIFS/PIFS-like cases, n = 4269 recovered control participants) with many studies excluded by inadequate quality in eligibility criteria. The meta-analysis (11 studies; n = 413 PIFS cases, analysed with random-effects models) showed PIFS cases had increased: white cell counts at 3-6 months (Cohen's d: 0.41, 95% CI 0.09-0.74); and circulating levels of RANTES and TNFα at 6-12 months (Cohen's d: 0.45 [95% CI 0.16-0.73] and 0.30 [95% CI 0.04-0.57], respectively) compared to controls recovered from the same exposure.

INTERPRETATION: These findings provide cautious support for persistent immune activation in PIFS, but warrant further replication. Future studies should include better documentation of acute infection and PIFS case characterisation.

FUNDING: ARL is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant 1041897). CXS is supported by a Cancer Institute New South Wales Early Career Fellowship (2021/ECF1310). BZK is supported by the National Institute of Allergy and Infectious Diseases (AI 105781). RE is supported by the National Institute for Health and Care.

RevDate: 2025-10-28
CmpDate: 2025-10-28

Mazzanti S, Barchiesi F, Pallotta F, et al (2025)

Severe Acute SARS-CoV-2 Infection and Long COVID: What Do We Know So Far? New Challenges in Diagnosis and Management.

Diseases (Basel, Switzerland), 13(10): pii:diseases13100337.

BACKGROUND/OBJECTIVES: The long-term impact of the COVID-19 pandemic is not just limited to socioeconomic aspects; there are also important health issues to consider. Among these, one of the most important and obvious is long COVID. Despite a significant amount of scientific work having been published, this condition is still semi-unknown. The objective of this study was to collect useful information for the clarification of some epidemiological, clinical, and laboratory characteristics of this disease.

METHODS: This was a single-center study carried out at the Infectious Diseases Clinic of the hospital "AUO delle Marche" on all patients hospitalized for COVID-19 between November 2021 and March 2022.

RESULTS: From the data, it emerged that, following the resolution of the acute phase of SARS-CoV-2 infection, the majority of people experienced health problems that persisted for at least 6 months. The manifestations and outcomes affect different systems; therefore, long COVID, like COVID-19, has systemic involvement and the clinical manifestations may be residues of the damage caused by the disease during the acute phase, or new manifestations whose pathogenesis is still a matter of discussion.

CONCLUSIONS: The persistence of inflammation and the dysregulation of the immune system represent some of the pathogenetic hypotheses. Inflammation could therefore represent one of the physiopathogenetic mechanisms of long COVID, and it is possible that it is responsible for the clinical symptoms that appear in the months following the resolution of the acute phase of the disease.

RevDate: 2025-10-28

Floridia M, Pagnanelli G, Piccinni G, et al (2025)

Persisting or recurrent dermatological manifestations in Long-COVID: Data from a national cohort of 1741 patients from Italy.

Journal of the American Academy of Dermatology pii:S0190-9622(25)02975-5 [Epub ahead of print].

RevDate: 2025-10-28
CmpDate: 2025-10-28

Padhye AS, Koralnik IJ, Hanson BA, et al (2025)

Blood diagnostic biomarkers for neurologic manifestations of long COVID.

Brain, behavior, & immunity - health, 49:101110.

BACKGROUND: SARS-CoV-2 responsible for COVID-19 caused a global pandemic, with billions of infections, millions of deaths and ongoing manifestations post COVID-19. "Long Covid", a Post-Acute Sequelae of COVID-19 (PASC), is an ongoing global healthcare problem, affecting all age groups, with many manifestations, and occurring despite vaccines and antivirals. Neurologic manifestations of PASC (Neuro-PASC) such as brain fog can last for years and are amongst the most debilitating and prevalent. There is a need for diagnostic tools and treatments.

METHODS: Plasma samples from 48 non-hospitalized PASC patients with diagnosed Neuro-PASC symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7000 proteins using the SomaLogic® proteomics platform. ProViz® software was used to perform T-tests, U-Tests, ANOVA and Kruskalis-Wallis tests at a Bonferroni p < 0.05 and a Benjamini-Hochberg corrected False Discovery Rate <0.02, and box plots and knowhow used to identify diagnostic biomarkers and therapeutic targets.

RESULTS: C5a, TGFβ1, and Gliomedin, used together differentiated patients with Neuro-PASC from control subjects with 94 % sensitivity and 86 % specificity, a 90 % accuracy. Additional biomarkers, Gal3ST1, IFNλ1, and GHRH, improved accuracy to 94 %, and a combination of 5 more biomarkers, LFA-3, FASLG + Transgelin-1 and GPNMB + IGHG1, improved accuracy close to 100 %. These markers are suggestive of pathways involved in Neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs.

CONCLUSION: C5a, TGFβ1, Gliomedin expressed highly in serum could be developed as a diagnostic tool, and with clinical assessment used to personalize treatments with repurposed novel drugs.

RevDate: 2025-10-28
CmpDate: 2025-10-28

Dudek A, Bursy M, Szkudlarek W, et al (2025)

Chronic Cardiovascular Disorders Associated With COVID-19: A Literature Review.

Cureus, 17(9):e93271.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is now widely recognized for causing several long-term effects known as post-COVID-19 syndrome (PCS) or long COVID (LC). This presents a growing challenge for healthcare systems worldwide. This narrative review summarizes original peer-reviewed studies indexed in PubMed and published between January 2020 and August 2025. It focuses on adult populations unless stated otherwise. We included studies that provided primary clinical or imaging data on chronic cardiovascular outcomes after confirmed SARS-CoV-2 infection. We excluded case reports, pediatric-only cohorts, and non-peer-reviewed sources. Among the various cardiovascular issues related to LC, we focused on heart fibrosis (HF), postural orthostatic tachycardia syndrome (POTS), new-onset hypertension (HT), and coagulopathy. These conditions consistently show up in the reports and are significant in terms of illness, potential long-term disability, and public health impact. Although these issues are distinct in their underlying causes, they share common mechanisms. These include ongoing inflammation of the endothelium, disruption of the renin-angiotensin-aldosterone system (RAAS), immune-related tissue damage, and an ongoing state that promotes blood clots. These processes can lead to measurable myocardial fibrosis that cardiac magnetic resonance imaging can detect, autonomic dysfunction often seen as POTS, a greater risk of developing hypertension shortly after infection, and a long-term rise in thromboembolic events due to increased clotting and resistant microclots. Current management is mostly focused on relief of symptoms and involves a team approach. It uses repurposed medications and tailored physical rehabilitation since no specific cure is available yet. Promising but still experimental methods, such as endothelial-protective agents like sulodexide and targeting inflammatory pathways, need thorough testing. There are significant gaps in our understanding of the long-term risk of hypertension, the natural progression of fibrosis, and the best treatment for POTS. This highlights urgent needs for future research. Beyond caring for individual patients, these ongoing cardiovascular problems raise important public health concerns. They include higher healthcare use, long-term disability, and economic costs. This situation requires increased clinical attention and proactive cardiovascular monitoring for those recovering from COVID-19.

RevDate: 2025-10-28
CmpDate: 2025-10-28

Blay N, Farré X, Garcia-Aymerich J, et al (2025)

Pre-pandemic disease trajectories and genetic insights into long COVID susceptibility.

BMC medicine, 23(1):590.

BACKGROUND: Long COVID refers to the persistence of symptoms after SARS-CoV-2 infection. While individual comorbidities have been studied, the role of coexisting chronic conditions remains underexplored. This study investigates whether pre-pandemic disease trajectories-sequential patterns of chronic conditions-modify long COVID risk and symptom profiles and explores shared genetic susceptibility.

METHODS: We analysed 8322 adult participants (58.6% women) from the COVICAT cohort (aged 40-65 at recruitment), followed between 2020 and 2023. Disease trajectories were reconstructed from electronic health records (2010-2019), focusing on sequences of two chronic conditions found in ≥ 1% of the cohort. We evaluated shared genetic architecture and polygenic risk scores (PRS) for predictive capacity.

RESULTS: Thirty-eight disease trajectories were associated with increased long COVID risk. These trajectories primarily involved mental and neurological disorders (e.g. depression, anxiety, migraine), respiratory diseases (e.g. asthma, allergic rhinitis) and cardiometabolic or digestive conditions (e.g. hypertension, lipidaemia, obesity, gastroesophageal reflux). No significant genetic correlations with long COVID were detected, but polygenic risk scores for two nervous system and musculoskeletal conditions showed modest associations with increased risk.

CONCLUSIONS: Disease trajectories were significantly associated with long COVID, with a sex effect, highlighting the importance of pre-pandemic disease trajectories. While no strong overall genetic correlations were found, modest polygenic associations suggest a role for shared susceptibility in nervous system and musculoskeletal disorders. From a public health perspective, identifying high-risk multimorbid individuals may inform targeted prevention and care strategies.

RevDate: 2025-10-28
CmpDate: 2025-10-28

Martins Conde P, Bulaev D, Rauschenberger A, et al (2025)

Co-occurrence of memory impairment and fatigue distinguishes post COVID from pandemic-related health effects in the 4-year CON-VINCE cohort study.

Scientific reports, 15(1):37381.

A major challenge in diagnosing post COVID lies in differentiating symptoms following a confirmed SARS-CoV-2 infection from those that may also occur in uninfected individuals (post COVID mimics) and be associated with a broader impact of the pandemic. The WHO post COVID definition was applied to the Luxembourgish longitudinal CON-VINCE cohort, where SARS-CoV-2 infection was confirmed via either a positive RT-qPCR or a serology test. Risk factor analysis was conducted on 1,865 individuals. Female gender, lower resilience, greater loneliness, and a higher number of comorbidities were associated with symptoms persistence. The symptomatology and comorbidity profiles of 559 participants (including 50 post COVID and 66 post COVID mimics) were investigated. Two distinct clusters of persistent symptoms were identified: (1) depression with anxiety, present in both infected and non-infected groups, and (2) memory impairment with fatigue, unique to the post COVID group. Therefore, presence of both memory impairment and fatigue may help differentiate post COVID patients from post COVID mimics. Yet, verification that memory impairment was newly developed was not possible, as this symptom was not recorded at baseline. Our findings suggest that future studies should consider factors affecting development of persistent post COVID-like symptoms observed in individuals that were never infected.

RevDate: 2025-10-28
CmpDate: 2025-10-28

Sujith S, N Gatzke (2025)

An overview of clinical presentation and management of long COVID.

The Nurse practitioner, 50(11):38-42.

The COVID-19 pandemic has been the 21st century's most significant public health emergency. In addition to the acute symptoms of COVID-19, many individuals are facing long-term health issues related to the infection. The terms "long COVID," "postacute sequelae of SARS-CoV-2 infection," "postacute COVID syndrome," and "long-haul COVID-19" refer to long-term consequences of SARS-CoV-2 infection. Symptoms may persist for weeks or months, reducing quality of life. Health practitioners must stay updated and take proactive measures to manage long COVID effectively. This manuscript provides an overview of risk factors, diagnostic tools, and management strategies, which serve as a resource for understanding and managing long COVID.

RevDate: 2025-10-27

Colaneri M, Galbussera AA, Tettamanti M, et al (2025)

Specialist Healthcare Intervention and Follow-up Trends in Post-Acute COVID-19 Hospitalization as Compared to Other Respiratory Infections.

Infectious diseases and therapy [Epub ahead of print].

INTRODUCTION: Post-acute sequelae of COVID-19, often referred to as "long COVID," have raised concerns about increased healthcare utilization following hospitalization. Whether these patterns differ significantly from those observed after other acute respiratory infections (ARIs) remains unclear. This study aimed to compare post-discharge healthcare use between patients hospitalized for COVID-19 and those with other ARIs in Lombardy, Italy.

METHODS: We conducted a population-based cohort study using 2021 administrative healthcare data from the Lombardy Region. Patients aged ≥ 40 years hospitalized for COVID-19 or other ARIs were followed for 12 months post-discharge. We evaluated specialist consultations, rehospitalizations, diagnostic testing, and new chronic drug treatment initiations. Logistic regression models adjusted for age, sex, and comorbidities (Drug-Derived Complexity Index) were used to assess differences.

RESULTS: Among 57,795 patients, 35,458 were hospitalized for COVID-19 and 21,375 for other ARIs. Patients with COVID-19 were younger and had lower comorbidity burden and post-discharge mortality (10.7% vs. 33.5%). A higher proportion received at least one specialist visit (75.8% vs. 70.3%), though with a longer median time to first visit (63 vs. 45 days, p < 0.0001). Patients with COVID-19 had more frequent imaging and spirometry but initiated fewer chronic drug treatments overall. However, a higher prescription rate for antidiabetics (OR 1.42), psychoanaleptic (OR 1.21), and genitourinary/hormonal drugs (OR 1.29) emerged after COVID-19 hospitalizations: this rate remained statistically higher for antidiabetics even after excluding subjects who died in the year following discharge. Hospitalizations for causes other than COVID-19 were more frequent in patients with ARI.

CONCLUSIONS: Compared to other ARIs, COVID-19 survivors exhibited distinct post-discharge healthcare patterns, with delayed but focused specialist care and selective increases in diagnostic and pharmacological interventions.

RevDate: 2025-10-27
CmpDate: 2025-10-27

Wehrli S, Hartner AM, Boender TS, et al (2025)

Information Pathways and Voids in Critical German Online Communities During the COVID-19 Vaccination Discourse: Cross-Platform and Mixed Methods Analysis.

Journal of medical Internet research, 27:e76309 pii:v27i1e76309.

BACKGROUND: In Germany, the messaging app Telegram (Telegram FZ-LLC) served as a tool to organize protests against public health measures during the COVID-19 pandemic. A community of diverse groups formed around these protests, which used Telegram to discuss and share views outside of the general public discourse and mainstream information ecosystem. This increasingly included conspiracy theories and extremist content, propagated by sources that opposed the mainstream positions of the government and traditional media. While the use of such sources has been thoroughly investigated, the role of mainstream information in these communities remains largely unclear.

OBJECTIVE: We aimed to better understand the use of mainstream information, that is, from government actors and established media outlets, within critical Telegram communities in the context of the COVID-19 pandemic in Germany. We focused on the discourse about the COVID-19 vaccination, a key public health measure. As a central element of this study, we compared the Telegram discourse with the discourse on X (formerly Twitter, X Corp) and in online news-this cross-platform analysis aimed to put the results into a broader societal context.

METHODS: We analyzed Telegram, X, and news data between 2019 and 2023 for popular topics related to the COVID-19 vaccination discourse. We used a mixed methods approach, including text clustering for the exploration of popular topics, a 2-stage keyword filtering scheme for multitopic classification, link sharing analysis for assessing the prevalence of mainstream information, correlation-based time series analysis for measuring the similarity of discourse dynamics, and thematic analysis to examine the reasons for sharing information.

RESULTS: We identified 5 popular vaccination-related topics that were discussed on both Telegram and X, namely death, long COVID, measures in schools, mandatory vaccination, and virus variants. On average per topic, 58% (SD 5.2%) of Telegram posts and 21% (SD 4.9%) of X posts contained an external link. Of these posts containing external links, 11%-35% of Telegram posts and 44%-60% of X posts contained a mainstream link per topic. The correlations for week-to-week changes in discourse intensity between Telegram, X, and online mainstream news ranged from no positive association (coefficient <0.2) to strong positive relationships (coefficient >0.6) per topic. Finally, the thematic analysis resulted in 5 themes describing the usage patterns of mainstream information on Telegram and X. The identified themes are observing news, news comments, directed accusations, participation, and reference in discussion (only X).

CONCLUSIONS: Mainstream information sources were part of the information mix within the analyzed critical Telegram communities. However, the role and prevalence of these sources varied. We argue that differences between platforms may indicate the existence of information voids, which pose a particular challenge in managing infodemics. These insights emphasize the importance of contextualized cross-platform analyses for understanding complex information pathways and their potential for targeted crisis communication.

RevDate: 2025-10-27
CmpDate: 2025-10-27

Hirschtick JL, Slocum E, Whittington B, et al (2025)

Comparison of survey questions to define long COVID: Implications for prevalence and disparities.

Preventive medicine reports, 59:103269.

OBJECTIVE: To understand whether variation in survey-based Long COVID estimates is partially due to how and when survey questions are asked.

METHODS: We compared Long COVID prevalence using distinct questions within a population-based, longitudinal survey of adults with confirmed SARS-CoV-2 before June 2022 in Michigan.

RESULTS: In our sample (n = 3826), 17.0 % reported symptoms for 90+ days at baseline, a median of 4.4 months after COVID-19 onset. A median of 18.4 months after COVID-19 onset, 24.5 % reported ever experiencing Long COVID, 16.9 % reported current Long COVID, and 10.8 % reported diagnosed Long COVID. Among adults without 90-day symptoms at baseline, 17.3 % reported ever Long COVID at follow-up. Relatedly, among adults with 90-day symptoms at baseline, 31.1 % reported they never had Long COVID at follow-up. After adjustment for reinfection, respondents who were Hispanic (vs. White) or lower income (<$75,000 vs. $75,000+) had greater odds of reporting baseline symptoms but never experiencing Long COVID at follow-up. Conversely, Black (vs. White) respondents had greater odds of reporting ever Long COVID at follow-up without baseline symptoms.

CONCLUSION: Surveys should employ several questions to define Long COVID and interpret findings within the context of factors likely contributing to discrepancies, including reinfection, stigma, awareness, and care-seeking behaviors.

RevDate: 2025-10-27
CmpDate: 2025-10-27

Kitsios GD, Li K, Blacka S, et al (2025)

Oral and gut microbiota relate to symptom subphenotypes in long COVID, independent of viral persistence.

iScience, 28(11):113628.

Long COVID presents a significant public health challenge, complicating diagnosis and treatment. In a prospective study of 349 individuals with long COVID (March 2021-December 2023), latent class analysis identified three symptom subphenotypes: high constitutional symptom burden (21%), predominant smell/taste disturbances (17%), and minimal persisting symptoms (62%). While viral persistence in saliva and stool was limited, 16S rRNA gene sequencing revealed microbiota associations with symptomatology. Alpha diversity was lower in individuals with high symptom burden, and specific taxa correlated with nausea and smell/taste disturbances. Distinct oral and gut microbiota patterns emerged across symptom clusters, with microbiota profiles also linked to patient-reported outcomes, including employment and overall health impact. These findings suggest that bacterial dysbiosis may contribute to long COVID symptom variability and highlight the microbiome's potential role in its pathophysiology. Understanding microbial influences on symptom persistence may inform microbiome-targeted therapeutic strategies and improve long COVID management.

RevDate: 2025-10-27
CmpDate: 2025-10-27

An H, Yu T, Wang A, et al (2025)

Persistent lymphocytopenia in convalescent patients with COVID-19: dysregulated B cell, CD4[+] T cell, and treg compartments in 7-12% of moderate-severe cases.

Frontiers in cellular and infection microbiology, 15:1693743.

BACKGROUND: Long COVID manifests with heterogeneous clinical outcomes, potentially linked to immune dysfunction. However, the recovery of immune-cell subsets during convalescence remains incompletely understood.

METHODS: In this longitudinal cohort, 279 unvaccinated patients with confirmed SARS-CoV-2 infection (13 mild, 218 moderate, 48 severe) were enrolled. Peripheral lymphocyte subsets were analyzed by flow cytometry at admission and at 50 days post-symptom onset (DPSO 50).

RESULTS: Total T-cell counts normalized in 90-98% of patients in the moderate and severe groups by DPSO 50. Nevertheless, a subgroup exhibited persistent B-cell lymphopenia (<90 cells/µL) in 7.3% of moderate cases (median 77.1 cells/µL, IQR 51.9-83.8) and 12.5% of seltvere cases (median 54.5 cells/µL, IQR 28.4-79.3). Patients with B-cell deficiency also showed concurrent reductions in total T cells, CD4[+] T cells, and CD4[+]CD25[+]CD127low/FOXP3[+] regulatory T cells (Tregs). In moderate cases, CD4[+] T cell and Treg counts correlated positively (r = 0.72, p < 0.001), independent of B-cell status, whereas this relationship was absent in severe cases, indicating severity-dependent immune dysregulation.

CONCLUSIONS: Approximately 7-12% of moderate-to-severe COVID-19 survivors displayed persistent lymphopenia affecting B cells, CD4[+] T cells, and Tregs at ~50 days post-symptom onset. These findings highlight distinct recovery trajectories and provide insights into Long COVID pathogenesis that may inform therapeutic strategies.

RevDate: 2025-10-27
CmpDate: 2025-10-27

Haq AM (2025)

Comment on "Pre-pandemic diabetes and risk of long COVID: Longitudinal evidence".

Journal of diabetes and metabolic disorders, 24(2):245.

RevDate: 2025-10-27

McCready JL, Campbell M, McCay K, et al (2025)

Optimising and beta-testing a user-centred, accessible, self-management rehabilitation smartphone app (reCOVer) for long-COVID fatigue using qualitative interview methods.

Disability and rehabilitation [Epub ahead of print].

PURPOSE: Fatigue is one of the most common and disabling symptoms of long-COVID, yet individuals often struggle to access appropriate services and must self-manage. This study aimed to adapt an existing smartphone app, originally developed for fatigue in autoimmune rheumatic disease, for individuals with long-COVID.

MATERIALS AND METHODS: A multidisciplinary steering group reviewed current clinical and scientific evidence to inform the adaptation of the app, reCOVer. The app includes an activity pacing diary, goal-setting tool, assertiveness and communication cards, and guidance on fatigue, sleep, relaxation, and setbacks. Beta-testing was conducted with 11 individuals with long-COVID (aged 21-57). Each participant took part in two serial qualitative interviews: the first explored their experience of fatigue and initial reactions to the app; the second, after 7-10 days of use, captured usability and acceptability feedback.

RESULTS: Participants found reCOVer helpful, particularly for increasing awareness of unhelpful patterns (e.g., boom-bust cycles) and supporting behaviour change through pacing. Communication tools were valuable when cognitive difficulties were prominent. Suggested improvements included text-to-speech functionality, clearer goal-setting instructions, and better articulation of app benefits.

CONCLUSIONS: reCOVer shows promise as a self-management tool for long-COVID fatigue. Further research, such as a pilot RCT, is needed to evaluate feasibility and effectiveness.

RevDate: 2025-10-25

Sano K, Kimura Y, Hirahata K, et al (2025)

SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID.

RevDate: 2025-10-25

Feter N, Caputo EL, Silveira da Silva L, et al (2025)

Long-term consequences of mental health distress during the COVID-19 pandemic on subjective memory decline: findings of the PAMPA cohort.

Public health, 249:105974 pii:S0033-3506(25)00420-2 [Epub ahead of print].

OBJECTIVES: While the acute impact of COVID-19 on mental health has been documented, less is known about its long-term consequences on cognitive health. We investigated the association between worsening depressive and anxiety symptoms during the pandemic with the risk of subjective memory decline over a three-year follow-up.

STUDY DESIGN: Prospective cohort study.

METHODS: We analyzed data from 682 adults participating in the PAMPA cohort, a longitudinal study in southern Brazil. Changes in depressive and anxiety symptoms were assessed at baseline (2020) and during the pre-pandemic period retrospectively. Subjective memory decline was self-reported in the fourth follow-up (2023). Robust Poisson regression was used to estimate associations. Inverse probability weighting was used to estimate selection bias.

RESULTS: Over follow-up, 51 % (95 %CI: 47.1 %-54.6 %) of participants reported subjective memory decline. Worsened depressive (RR: 1.33; 95 %CI: 1.21-1.64) and anxiety (RR: 1.36; 95 %CI: 1.28-1.44) symptoms were associated with a higher risk of subjective memory decline. Each one-point increase in depression (RR = 1.04; 95 % CI: 1.03-1.05) and anxiety (RR = 1.02; 95 % CI: 1.01-1.03) symptoms was linked to a 4.3 % and 2.4 % increase in the risk of subjective memory decline. Associations remained robust after adjusting for COVID-19 status and other potential confounders, including depressive and anxiety symptoms at follow-up. Results were consistent in sensitivity analyses excluding participants with long COVID.

CONCLUSION: Worsening mental health during the COVID-19 pandemic predicted subjective memory decline three years later. Our findings underscore the importance of mental health support as a public health strategy to preserve long-term cognitive function, particularly after large-scale crises.

RevDate: 2025-10-25

Badhwar S, Pereira TJ, Kerr K, et al (2025)

Autonomic phenotyping, brain blood flow control, and cognitive-motor-integration in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.

Autonomic neuroscience : basic & clinical, 262:103358 pii:S1566-0702(25)00120-1 [Epub ahead of print].

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the prolonged sequelae after COVID-19 (>3 months; Long COVID) have similar symptomology, are both associated with autonomic dysfunction, and a growing proportion of Long COVID patients are developing ME/CFS. We aimed to determine an autonomic phenotype of patients with ME/CFS vs Long COVID. We hypothesized that the groups would differ from controls yet be similar to one another. We recruited sedentary controls (n = 10), mild/moderate ME/CFS patients (n = 12), and Long COVID patients (n = 9) to undergo 1) breathing 5 % CO2, 2) breathing 10 % O2, and 3) 5-minutes of 70° head-up tilt. Respiratory, hemodynamic, and cerebrovascular variables were measured throughout the 3 trials. Resting vascular function and cognitive-motor-integration were also assessed. ME/CFS and Long COVID were similar to the healthy controls and each other with regard to resting vascular function and the hemodynamic responses to hypoxia, hypercapnia, and head-up tilt (p > 0.05). However, in ME/CFS we observed a greater reduction of cerebrovascular resistance (p = 0.041) and impaired autoregulation (p = 0.042) during hypercapnia alongside impaired cognitive-motor integration (p < 0.02), and in Long COVID we observed reduced peripheral and end-tidal oxygen (p < 0.04) and less vagal withdrawal during tilt (p = 0.028). Our findings suggest unique phenotypes when comparing ME/CFS and Long COVID whereby we have shown that Long COVID patients experience hypoxia while upright contributing to less vagal withdrawal, and ME/CFS patients experience impaired cerebrovascular control during hypercapnia potentially leading to reduced cognitive-motor integration. These differences could stem from disease severity/duration or some unique aspect of the COVID-19 virus.

RevDate: 2025-10-25

Yamamoto K, Inoue T, Ikeda T, et al (2025)

Efficacy of Lactococcus lactis Strain Plasma in Patients with Mild COVID-19: A Multicenter, Double-Blinded, Randomized-Controlled Trial (PLATEAU Study).

Infectious diseases and therapy [Epub ahead of print].

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still an ongoing public health threat. COVID-19 can be accompanied by prolonged symptoms, known as "long COVID", however, no pharmaceutical treatments are currently available for these symptoms. Lactococcus lactis strain Plasma (LC-Plasma; Lactococcus lactis subsp. lactis JCM 5805) directly activates human plasmacytoid dendritic cells (pDCs) and triggers antiviral immune responses. We hypothesized that LC-Plasma reduced SARS-CoV-2 viral load and eased symptoms in patients with mild COVID-19.

METHODS: This PLATEAU study enrolled 100 patients with mild COVID-19 during Omicron BA.1 endemic, who were randomized into the LC-Plasma or placebo group in a 1:1 ratio and were observed for 14 days. The primary endpoint was change in total score of eight subjective symptoms (fatigue, anorexia, headache, cough, shortness of breath, chest pain, smell, and taste disturbance). Secondary endpoints included each symptom, SARS-CoV-2 viral load, and pDCs.

RESULTS: The primary endpoint did not show between-group differences. However, the proportion of patients without smell and taste disturbances was significantly higher in the LC-Plasma group on day 13 (p = 0.030). The LC-Plasma group showed a significantly earlier decrease in SARS-CoV-2 viral load on day 4 (p < 0.001) and an increase in pDCs on day 8 (p = 0.0498). Mild adverse events, such as diarrhea, cough-variant asthma, and urticaria, occurred in three (5.9%) patients in the LC-Plasma group.

CONCLUSIONS: The intake of LC-Plasma in patients with mild COVID-19 activates pDC, decreases SARS-CoV-2 viral load earlier, and may improve smell and taste disorders more quickly. LC-Plasma could be a safe, inexpensive, and easily accessible tool for the treatment of mild COVID-19.

TRIAL REGISTRATION: jRCTs071210097.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Miller AJ, Wei G, Stoddard GJ, et al (2025)

Pre-existing comorbidities and hospitalization for COVID-19 are associated with post-COVID conditions in the U.S. veteran population.

Communications medicine, 5(1):442.

INTRODUCTION: Although most survivors of COVID-19 return to their baseline health within two weeks, a notable proportion of individuals continue experiencing symptoms, collectively referred to as Post-COVID Conditions (PCC). To better understand risks associated with contracting PCC, this study aimed to determine whether association exists between pre-existing comorbidities, hospitalization for COVID-19 and the subsequent diagnosis of PCC in US veterans.

METHODS: This retrospective cohort study collected data from the US Department of Veterans Affairs electronic medical records from September 1, 2021, to July 31, 2023. Participants were limited to those with electronic medical records of a SARS-CoV-2 infection, who received care from the Veterans Affairs hospital system and survived at least 28 days following the infection.

RESULTS: The multivariable logistic regression analysis reveals in hospitalized veterans, chronic obstructive pulmonary disease (COPD) associates with a 21% increase in odds of a PCC diagnosis (adjusted OR 1.21, 95%CI 1.14-1.29; p < 0.001), while in non-hospitalized veterans, chronic kidney disease (OR 1.09 95%CI 1.03-1.15; p = 0.001)) and COPD (OR 1.33, 95%CI 1.27-1.40; p < 0.001) demonstrate an increase in odds of a PCC diagnosis. Additionally, unvaccinated and partially vaccinated veterans exhibit significantly higher odds for PCC (p < 0.001) compared to fully vaccinated veterans in both the hospitalized and non-hospitalized cohorts. Increasing age, increasing BMI, female sex, Hispanic ethnicity, and veterans residing in the Southwestern United States show a significant (p < 0.05) increase in risk for a positive diagnosis of PCC in both groups.

CONCLUSIONS: Veterans with pre-existing COPD or those hospitalized at the time of COVID-19 (indicating disease severity) are at higher risk of receiving a PCC diagnosis.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Georgopoulos AP, James LM, PK Peterson (2025)

HLA and pathogens in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other post-infection conditions.

Scientific reports, 15(1):37303.

Viral infections have been widely implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) pathogenesis. Recent evidence has also identified certain Human Leukocyte Antigen (HLA) alleles that are significantly associated with ME/CFS risk/protection. Here we tested the hypothesis that ME/CFS risk or protection conferred from those HLA alleles is associated with binding affinity to antigens of HHV viruses, a critical step in initiating the adaptive immune system response to foreign antigens. Specifically, we determined in silico the predicted binding affinity of two susceptibility alleles (C*07:04, DQB1*03:03) and two protective alleles (B*08:01, DPB1*02:01) to > 10,000 antigens of the 9 Human Herpes Viruses (HHV1, HHV2, HHV3, HHV4, HHV5, HHV6A, HHV6B, HHV7, HHV8) which have been implicated in the etiology of ME/CFS. We found that the binding affinity of all HHV antigens to the susceptibility alleles was significantly weaker than the binding affinity to the protective alleles (P < 0.001). In fact, none of the HHV antigens showed strong binding to the susceptibility alleles, in contrast to the strong bindings showed by the protective alleles. These findings are in keeping with the hypothesis that the effect of a putative HHV insult in contributing to ME/CFS is modulated by the host's HLA immunogenetic makeup. We speculate that strong HLA-antigen binding likely protects against ME/CFS via elimination of virus antigens; conversely, weak HLA-antigen binding may permit persistence of foreign antigens, contributing to ME/CFS and other chronic conditions. Finally, with respect to the latter, we determined the binding affinities to the 4 HLA alleles above to pathogens causing two chronic diseases with very similar symptomatology to ME/CFS, namely Long COVID and post-treatment Lyme disease syndrome (PTLDS). We found that the 2 ME/CFS susceptibility HLA alleles above had very weak binding with SARS-CoV-2 virus glycoprotein (involved in Long COVID) and 5 proteins of Borrelia burgdorferi (involved in PTLDS), in contrast to the ME/CFS protective alleles that showed strong bindings. These findings support the hypothesis that ME/CFS, long COVID and PTLDS are caused by persistent pathogenic antigens that could not be eliminated due to inadequate protection by the patient's HLA makeup.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Botdorf M, Dickinson K, Lorman V, et al (2025)

Identifying Pediatric Long COVID: Comparing an EHR Algorithm to Manual Review.

Applied clinical informatics, 16(5):1445-1456.

Long COVID, characterized by persistent or recurring symptoms post-COVID-19 infection, poses challenges for pediatric care and research due to the lack of a standardized clinical definition. Adult-focused phenotypes do not translate well to children, given developmental and physiological differences, and pediatric-specific phenotypes have not been compared with chart review.This study introduces and evaluates a pediatric-specific rule-based computable phenotype (CP) to identify long COVID using electronic health record data. We compare its performance to manual chart review.We applied the CP, composed of diagnostic codes empirically associated with long COVID, to 339,467 pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The CP identified 31,781 patients with long COVID. Clinicians conducted chart reviews on a subset of patients across 16 hospital systems to assess performance. We qualitatively reviewed discordant cases to understand differences between CP and clinician identification.Among the 651 reviewed patients (339 females, M age = 10.10 years), the CP showed moderate agreement with clinician identification (accuracy = 0.62, positive predictive value [PPV] = 0.49, negative predictive value [NPV] = 0.75, sensitivity = 0.52, specificity = 0.84). Performance was largely consistent across age and dominant variant but varied by symptom cluster count. Most discrepancies between the CP and chart review occurred when the CP identified a case, but the clinician did not, often because clinicians attributed symptoms to preexisting conditions (73%). When clinicians identified cases missed by the CP, they often used broader symptom or timing criteria (69%). Model performance improved when the CP accounted for preexisting conditions (accuracy = 0.71, PPV = 0.65, NPV = 0.74, sensitivity = 0.59, specificity = 0.79).This study presents a CP for pediatric long COVID. While agreement with manual review was moderate, most discrepancies were explained by differences in interpreting symptoms when patients had preexisting conditions. Accounting for these conditions improved accuracy and highlights the need for a consensus definition. These findings support the development of reliable, scalable tools for pediatric long COVID research.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Andrassy B, Tallada S, Harris M, et al (2025)

Stellate Ganglion Block for Headache Pain and Cognitive Impairment Associated With Long COVID Persisting Over 12 Months: A Case Report.

Pain medicine case reports, 9(6):305-309.

BACKGROUND: Postacute sequelae of COVID-19 (PASC) are debilitating health conditions affecting over 7% of the US population. Clinical PASC manifestations are variable, but consistently involve dysautonomia and elevated inflammatory biomarkers. Common symptoms include pain, fatigue, cognitive impairment, sensory loss, and orthostatic intolerance. As neuroimmune hyperactivation and reductions in cerebral blood flow are each implicated in PASC pathophysiology, stellate ganglion block (SGB) represents a promising treatment option due to its ability to reset autonomic activity and reperfuse the brain. We sought to retrospectively assess the potential of SGB to treat head and neck pain, cognitive impairment, and fatigue associated with PASC persisting over 12 months.

CASE REPORT: We reviewed and analyzed case data from 2 middle-aged female patients with painful, longstanding PASC managed with repeat unilateral SGB. Procedures were performed under ultrasound guidance, with 3 mL 0.5% bupivacaine + 12 mg betamethasone as the injectate. Each patient received 2 SGBs, with all procedures being tolerated well. No complications occurred. One patient had a recurrence of migraine pain following the blocks, while the other experienced durable relief. Both patients saw improvements in cognitive function and fatigue postoperatively, which were sustained.

CONCLUSIONS: Most literature on SGB for PASC management concerns its ability to reverse sensory loss, rather than relieve chronic pain. This case report provides preliminary evidence supporting the effectiveness of SGB for managing pain and cognitive impairment in PASC. As PASC symptoms with longer durations tend to be less effectively managed with SGB, we speculate that chronicity of the patients' symptoms hampered SGB-mediated pain relief.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Durstenfeld MS, Mataraarachchi N, Peluso MJ, et al (2025)

Case-control study of autonomic symptoms in the setting of Long COVID with tilt table testing.

PloS one, 20(10):e0335218 pii:PONE-D-25-34093.

BACKGROUND: Autonomic symptoms and orthostatic syndromes have been reported in Long COVID, but few studies have characterized findings using head up tilt table testing.

OBJECTIVE: To characterize autonomic responses to positional changes among individuals with Long COVID.

METHODS: We assessed autonomic symptoms using the Composite Autonomic Symptom Scale 31 (COMPASS 31) instrument and performed head up tilt table testing for 30 minutes at 70 degrees among individuals with Long COVID and recovered comparators.

RESULTS: We included 26 participants (median age 56 years, 50% female median 25 months after first COVID): 16 with Long COVID and 10 recovered comparators. COMPASS 31 scores (0-100, higher is worse) were higher among those with Long COVID (median 30.5 vs 8, p = 0.003). Heart rate was 8 beats per minutes higher throughout tilt among those with Long COVID (95% CI 1.1 to 14.4; p = 0.02); there were no differences in blood pressure. Ten (63%) with Long COVID had symptoms during tilt compared to none among recovered participants (p = 0.003). Three (19%) with Long COVID had clinically abnormal findings: one each with orthostatic hypotension, and delayed orthostatic hypotension, and cardioinhibitory/vasovagal presyncope.

CONCLUSIONS: Among those with chronic autonomic symptoms in the setting of Long COVID, symptoms were common during tilt testing, and heart rate was increased, but most did not meet diagnostic criteria for a clinically abnormal hemodynamic response. Further research into mechanisms of autonomic symptoms in Long COVID is urgently needed.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Algera E, Maukner AC, van Dorth J, et al (2025)

'I Do Take the Number Seriously, but I Don't Let My Moods Depend on It': Negotiating Self-Tracking Data With People Living With Long COVID in the Netherlands, Austria and Switzerland.

Sociology of health & illness, 47(8):e70102.

For many people living with long COVID (PWLC), self-tracking has emerged as a valuable practice to monitor their illness. An examination of self-tracking practices can, therefore, shed light on the ways in which individuals navigate their care, make sense of their experiences and advocate for their needs. This study investigates how PWLC engage in self-tracking practices and how they utilise and negotiate the data generated. Based on 33 semi-structured interviews with PWLC in the Netherlands, Austria and Switzerland, we found that PWLC use self-tracking to recognise patterns and identify limits, triggers and effective interventions. The insights drawn from this are used to make informed decisions about health management strategies. Yet, self-tracking may also reify symptoms and negatively influence the subjective illness experience, exacerbating stress and anxiety. Although PWLC themselves negotiate and question their tracking data, they find a variety of responses from healthcare providers in clinical interactions. Using the concept of 'trading zone' (Kjærulff and Langstrup), we argue that although self-tracking cannot replace treatment and good care, its integration into the healthcare experience as a valuable form of patient knowledge may improve the patient-provider relationship.

RevDate: 2025-10-24

Abbasi J (2025)

New Guidance on Cardiovascular Disease and COVID-19-From Infection to Long COVID to Vaccination.

JAMA pii:2840667 [Epub ahead of print].

RevDate: 2025-10-24
CmpDate: 2025-10-24

Vernon SD, Rond C, Sun Y, et al (2025)

Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome.

Frontiers in neurology, 16:1691147.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by fatigue, cognitive impairment, and reduced physical function. Oxaloacetate (OAA), a metabolic compound with potential mitochondrial and neuroprotective effects, has shown promise in reducing fatigue symptoms in ME/CFS. However, the interrelationships between fatigue, cognitive performance, and physical activity and their responsiveness to treatment remain poorly understood in ME/CFS.

METHODS: This 90-day randomized, double-blind, controlled trial evaluated the effects of 2,000 mg/day OAA or a control of 2,000 mg rice flour in 82 adults with ME/CFS. Self-reported fatigue (Chalder Fatigue Questionnaire), cognitive function (DANA Brain Vital), and upright activity time (UP Time) were assessed at baseline and three follow-up visits. Linear mixed-effects models examined associations between fatigue severity and cognitive/physical function, with treatment group interactions. Responder status at the last visit (Visit 4) was classified based on ≥15% fatigue reduction and/or ≥10% cognitive improvement.

RESULTS: The OAA group showed greater cognitive improvement over time, with a significant between-group difference at Visit 3, 60 days into the trial, (p = 0.034) and trends at other visits. Higher fatigue was significantly associated with reduced cognitive gains in the OAA group (β = -0.34, p < 0.0001), but not in controls. UP Time increased modestly in the OAA group, reaching significance at Visit 2, day 30 (p = 0.044), though fatigue was not a strong predictor of UP Time in either group. At Visit 4, day 90, Global and Fatigue Only Responders were more frequent in the OAA group, while Cognitive Only Responders were more frequent in controls, though group differences did not reach statistical significance (p = 0.10).

CONCLUSION: OAA supplementation was associated with improved cognitive performance and small improvement in UP Time in ME/CFS participants receiving OAA. Fatigue-cognition coupling was particularly strong in OAA-treated participants, suggesting a potentially targetable phenotype. These findings underscore the importance of multidimensional outcome measures in ME/CFS clinical trials and support the need for more research and trials of metabolic interventions in ME/CFS.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Sawyer A, Preston R, Leeming H, et al (2025)

Wearable technology in the management of complex chronic illness: preliminary survey results on self-reported outcomes.

Frontiers in digital health, 7:1662255.

INTRODUCTION: Complex chronic illnesses like Long Covid (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are marked by fluctuating symptoms, often exacerbated by physical, cognitive, or emotional exertion in a phenomenon known as post-exertional malaise (PEM). Home monitoring technologies offer potential benefits by enabling individuals to track symptoms and biometrics, aiding in disease self-management. However, the general effectiveness of such tools is still unknown.

METHODS: A random sample of users of the Visible mobile application (Visible Plus; requires both the armband and paid subscription), aged 18 or older and with self-identified complex chronic illnesses such as LC or ME/CFS, were invited to complete an online survey regarding the impact of the app on their chronic disease self-management. Descriptive statistics related to the responses were analyzed and reported.

RESULTS: The survey was distributed to 2,636 people, with 1,301 participants responding (49.3% response rate). The average age was 46 years. 82% of respondents were female, 8% were male, 8% were non-binary, and 2% preferred not to say or preferred to self-describe. Participants self-identified as having ME/CFS only (n = 534, 42%), LC only (n = 396, 31%), ME/CFS and LC (n = 236, 18%), or another illness (n = 122, 10%). Of the n = 2,636 randomly selected subscribers, the mostly commonly listed "other illnesses" were Postural Orthostatic Tachycardia Syndrome (POTS, 6%), fibromyalgia (5.2%), Ehlers Danlos Syndrome (EDS; 1.7%) and Mast Cell Activation Syndrome (MCAS, 1.2%). Of those with at least 30 days of data, 77% reported seeing an improvements associated with app use, corresponding to 23% of all invited users, 85% (corresponding to 29% of all invited users) reported feeling somewhat (53%) or significantly (32%), and 94% (corresponding to 33% of all invited users) reported a better understanding of their energy budget.

DISCUSSION: Home-monitoring based mobile applications are feasible and acceptable for a motivated subgroup of people with energy-limiting complex chronic illnesses, and are associated with self-reported benefits in energy management and participation in daily activities. The findings of this study should be interpreted as descriptive and hypothesis-generating and do not represent clinically significant effects, underscoring the need for randomized controlled trials to formally evaluate efficacy. Future studies should incorporate a comparison group to better differentiate intervention effects from improvements gained through lived experience.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Lo M, Eiriksson L, Hunter S, et al (2025)

Individually Tailored Physiotherapy in Persons With Respiratory Symptoms Related to Post-Acute Sequelae of COVID-19: A Feasibility Study With Mixed Methods.

Health science reports, 8(10):e71367.

BACKGROUND AND AIMS: Post-acute sequelae of COVID-19 (PASC) commonly present with persistent respiratory symptoms, even in individuals with normal chest imaging and pulmonary function. Given the heterogeneity within this population, a personalized approach to respiratory physiotherapy could improve outcomes. The purpose of this study was to assess the feasibility and impact of a tailored respiratory physiotherapy program on health-related quality of life (QoL), functional impairment, and patient-reported outcome measures (PROMs) in individuals with persistent respiratory symptoms due to PASC.

METHODS: A single-arm, open-label trial was conducted with 13 adults diagnosed with PASC, recruited from Long COVID clinics in Calgary, Canada. Participants underwent an 8-session personalized physiotherapy program, including education, breathing exercises, and strengthening. Feasibility was measured through recruitment, retention, and session completion rates. PROMs were collected at baseline and post-intervention, and qualitative interviews explored participant perspectives.

RESULTS: The program was highly feasible, with 100% retention and a 99% completion rate. Significant improvements were observed in QoL, functional status (Post COVID-19 Function Status scale), and self-efficacy scores. The 6-min walk test showed clinically meaningful improvements in three out of seven participants. Qualitative interviews (n = 8) identified three main themes: struggles with PASC, positive aspects of the program, and benefits from completing it. Participants valued the personalized approach, heart rate monitors, flexible scheduling, and a hybrid of in-person and virtual sessions, reporting increased confidence, improved symptom management, and better mental health.

CONCLUSION: A personalized respiratory physiotherapy program is feasible and may benefit individuals with PASC. Larger trials are needed to assess long-term efficacy and scalability.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05040893.

RevDate: 2025-10-24
CmpDate: 2025-10-24

Shan D, Holland C, TJ Crawford (2025)

Treatment experiences, preferences, and expectations for cognitive impairments in long COVID among Chinese young and older adults: a constructivist grounded theory study.

BMC medicine, 23(1):579.

BACKGROUND: Cognitive impairments associated with long COVID disrupt daily functioning and psychological well-being. While increasing research has examined prevalence and mechanisms, little is known about patients' treatment experiences, preferences, and expectations. In the absence of validated effective treatments, integrating these perspectives is essential for guiding research priorities and clinical trial design. In China, where long COVID is an emerging public health concern, awareness of cognitive impairments remains limited and access to specialised care is inadequate. Considering potentially substantial differences in baseline health and treatment expectations between young and older adults, this study aimed to explore and compare their perspectives using a qualitative approach.

METHODS: We adopted constructivist grounded theory to capture participants' lived experiences and develop a theory grounded in their narratives. Semi-structured online interviews were conducted with 23 individuals recruited via Chinese social media long COVID mutual aid groups, including 10 young adults (18-39 years) and 13 older adults (≥ 60 years). Theoretical sampling guided recruitment and iterative analysis through initial, focused, and theoretical coding, leading to the development of a framework explaining treatment preferences and expectations.

RESULTS: All participants reported cognitive impairments based on self-perception, with no formal medical diagnoses. We constructed a theoretical framework of "Individualised and Dynamic Adaptation to Cognitive Challenges". Preferences and expectations could be shaped by age, symptom severity, prior management experiences, lifestyle, doctor-patient interactions, and health literacy. Young adults showed a strong preference for non-pharmacological strategies, including self-directed approaches and emotional support to address stigma. Older adults emphasised a balanced use of pharmacological and non-pharmacological interventions, supported by family and structured routines, while expressing holistic expectations that encompassed cognitive, physical, and emotional well-being. Across both groups, improved sleep and psychological health were consistently emphasised.

CONCLUSIONS: Age-specific differences highlighted the heterogeneity of long COVID experiences and underscored the need for dynamic, patient-centred approaches. Tailored interventions that integrate patient perspectives may enhance care quality and outcomes. Holistic care, particularly for older adults who may face additional comorbidities and functional challenges, is essential. In China, increasing awareness among the public and healthcare providers, reducing stigma, and addressing inequalities in care access should be prioritised.

RevDate: 2025-02-25

Sujith S, N Gatzke (2025)

Caring for youth in foster care: A trauma-informed practice guide.

The Nurse practitioner, 50(3):38-39.

The COVID-19 pandemic has been the 21st century's most significant public health emergency. In addition to the acute symptoms of COVID-19, many individuals are facing long-term health issues related to the infection. The terms “long COVID,” “postacute sequelae of SARS-CoV-2 infection,” “postacute COVID syndrome,” and “long-haul COVID-19” refer to long-term consequences of SARS-CoV-2 infection. Symptoms may persist for weeks or months, reducing quality of life. Health practitioners must stay updated and take proactive measures to manage long COVID effectively. This manuscript provides an overview of risk factors, diagnostic tools, and management strategies, which serve as a resource for understanding and managing long COVID.

RevDate: 2025-10-23

Masoodi WTA, Radhi SW, Al-Hakeim HK, et al (2025)

Trace Element Imbalance as a Possible Factor in Long-COVID Pathophysiology: Links to Disease Duration and Inflammation.

The American journal of the medical sciences pii:S0002-9629(25)01250-9 [Epub ahead of print].

BACKGROUND: Long-COVID is defined by persistent symptoms following an initial COVID-19 infection. The normal immune function depends on a precise balance of trace elements, which can provide fresh insights into prospective therapeutic strategies while maintaining oxidative balance and limiting excessive inflammation. Zinc, copper, cobalt, and manganese deficits or excesses can alter the immune system's normal functions and oxidative stress. The study aims to study the trace element profile for predicting long-COVID.

METHODS: The levels of serum copper and zinc were measured spectrophotometrically. In contrast, cobalt and manganese were measured using flameless atomic absorption spectrophotometry in 60 long-COVID patients and compared with the 30 controls who had previous SARS-CoV-2 infection but were free from long-COVID symptoms.

RESULTS: Serum levels of copper, cobalt, manganese, and the copper/zinc ratio were considerably elevated in long-COVID patients compared to the control groups. Nonetheless, there was no significant change in zinc levels relative to the control group. The cobalt concentration increases with the duration of the disease and inflammation. Serum manganese level is significantly and negatively correlated with weight. The duration of disease is inversely linked to serum zinc concentrations. There is a substantial correlation between serum copper levels and the period of recovery from acute SARS-CoV-2 infection.

CONCLUSIONS: Long-COVID is associated with alterations in serum trace elements (copper, cobalt, and manganese). The imbalances in the trace elements are associated with inflammation, duration of disease, and age. These imbalances may contribute to prolonged symptoms and greater disease severity, suggesting that trace element monitoring could be beneficial in managing long-COVID.

RevDate: 2025-10-23

Adesse D, Torices S, Alcaide ML, et al (2025)

Plasma biomarkers of neurogenesis are increased among people with HIV after COVID.

Journal of acquired immune deficiency syndromes (1999) pii:00126334-990000000-00736 [Epub ahead of print].

OBJECTIVES: While acute COVID does not appear to markedly differ by HIV status, the long-term impact of COVID in people with HIV (PWH) remains unclear.

METHODS: Samples from forty-four participants with or without HIV were obtained approximately 10 days after the initial COVID diagnosis (t=0) and then three (t=1) and six (t=2) months later. Biomarkers of blood brain barrier (BBB) and vascular dysfunction, neurogenesis, and inflammatory responses were assessed by multiplex profiling and ELISA.

RESULTS: The majority of inflammatory biomarkers either decreased or remained unchanged over the evaluated time frame. Notable exceptions were IL-9, TNF-α, and CCL-4, which increased at t=2 compared to earlier time points. The BBB disruption and vascular dysfunction biomarkers (S100β and soluble ICAM1, respectively) increased at t=1 and then returned to basal levels, suggesting transient loss of BBB integrity. No significant changes were observed between people without HIV (PWOH) and PWH across studied inflammatory and BBB markers. Among biomarkers of neurogenesis, eotaxin/CCL11 was not altered, FGF-2 was transiently decreased at t=1 in PHW, and G-CSF was elevated at t=2 in PWH when compared to the previous time-points.

CONCLUSIONS: BBB and vascular dysfunction occur after COVID and may be implicated in the development of post-COVID conditions. HIV-1 infection may potentiate post COVID-induced neuropathology by impairing neurogenesis.

RevDate: 2025-10-23
CmpDate: 2025-10-23

Escobar Villegas PA, Cordoba-Melo BD, Arango-Ibanez JP, et al (2025)

Xerostomia in survivors of severe COVID-19: findings from a Latin American cohort.

Frontiers in oral health, 6:1633542.

OBJECTIVES: SARS-CoV-2 primary affects the respiratory tract; however, evidence suggests the oral cavity can be involved in severe COVID-19 survivors. This study investigates factors associated with xerostomia in severe COVID-19 survivors from a Latin American cohort.

MATERIALS AND METHODS: A prospective multicenter study from the Latin American Registry of Cardiovascular Disease and COVID-19, analyzed data on 272 severe COVID-19 patients from 7 institutions in 5 countries (Colombia, Dominican Republic, Ecuador, Argentina, and Paraguay). Long-term follow-up assessed demographics characteristics, comorbidities, lifestyle, cardiovascular complications, and oral health. Logistic regression in R software identified factors associated with xerostomia.

RESULTS: Xerostomia was reported in 20.6% of patients. Among affected individuals, 53.6% were female, while women represented 35.6% of those without the condition. In the overall cohort, the most common comorbidities were overweight/obesity (57.0%), hypertension (55.9%), and dyslipidemia (32.0%). Patients with xerostomia had higher rates of dyslipidemia (48.2% vs. 27.8%) and asthma/COPD (16.1% vs. 4.2%) compared to the group without xerostomia. In multivariable logistic regression, asthma/COPD (aOR: 5.14; 95% CI: 1.76-15.7), palpitations (aOR: 2.47; 95% CI: 1.04-5.94), and chest pain (aOR: 3.74; 95% CI: 1.67-8.43) were independently associated with xerostomia. Conversely, male sex was associated with lower odds of reporting xerostomia (aOR: 0.47; 95% CI: 0.24-0.89).

CONCLUSION: These findings underscore the need for clinicians to actively assess oral health symptoms such as xerostomia in post-COVID care, particularly in patients with cardiopulmonary comorbidities and persistent systemic symptoms.

RevDate: 2025-10-23
CmpDate: 2025-10-23

Engelberts R, Douglass CH, Orozco A, et al (2025)

Understanding Long COVID Among Young People in Victoria, Australia: Prevalence, Impact, and Associated Factors.

Public health challenges, 4(4):e70144.

INTRODUCTION: Long COVID is a significant public health concern. This study aimed to identify the prevalence, impact, and factors associated with long COVID among young people in Victoria, Australia.

METHODS: From April to June 2023, we conducted a cross-sectional online survey of people aged 15-29 years. Participants reported if they had ever experienced long COVID (defined as COVID-19 symptoms for more than 4 weeks) and the impact on their daily functioning. We used multivariable logistic regression to compare participants who reported long COVID with participants who reported acute COVID-19.

RESULTS: Among 765 participants, 11.2% reported they had ever had long COVID; however, only 1 in 10 had been diagnosed by a medical practitioner. Compared to those without prolonged symptoms, participants reporting long COVID were younger (adjusted odds ratio [aOR]: 0.92; 95% confidence interval [CI]: 0.85-0.99), reported worsened general health (aOR: 8.22; 95% CI: 4.34-15.56), expressed greater concern about getting long COVID again (aOR: 1.20; 95% CI: 1.09-1.33), and had more family or friends who also experienced long COVID (aOR: 4.43; 95% CI: 1.92-10.19). In the past 4 weeks, 79.1% of participants with current long COVID reported difficulties with performing work, and 79.1% accomplished less than desired.

CONCLUSIONS: One in 10 participants aged 15-29 years experienced long COVID, and most reported negative impacts on their daily life. General practitioners should be aware of the high burden of suspected long COVID in young people and consider supports to mitigate its effects on the health and well-being of this population.

RevDate: 2025-10-23
CmpDate: 2025-10-23

Poulakou G, Michailidis V, Gogali A, et al (2025)

Real-world evidence on long COVID-19 in Greece: A multicenter, cross-sectional study (LONCOV2).

IJID regions, 17:100761.

OBJECTIVES: This study aimed to provide real-world data on the clinical presentation and management of long COVID in Greece.

METHODS: This non-interventional, nationwide, multicenter, cross-sectional study included adults with a history of symptomatic SARS-CoV-2 infection who presented with suspected long-term COVID-19 manifestations ≥4 weeks after acute infection.

RESULTS: Among 1011 patients (mean ± SD age: 55.95 ± 15.74 years; 56.18% female; 5.04% hospitalized) enrolled between December 2022 and May 2023, the most affected Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) was General disorders and administration site conditions (75.67%), with fatigue/malaise as the predominant symptom (69.93%). This was followed by Respiratory, thoracic, and mediastinal disorders (60.34%), with cough (50.64%) and dyspnea (24.83%) as leading symptoms. Social circumstances, specifically impairments in daily living activities (44.21%), Nervous system disorders (40.26%), mainly headache (23.24%), and Musculoskeletal and connective tissue disorders (27.70%), mainly myalgia (24.63%), were also prominent. The majority (74.38%) had been vaccinated prior to infection, with vaccination shown to be protective against nervous and musculoskeletal symptoms. Females were more prone to systemic, psychiatric, nervous, and musculoskeletal symptoms and impairments in daily activities, but less prone to respiratory symptoms.

CONCLUSIONS: Multisystem long-term COVID-19 complications were observed, underscoring the importance of multidisciplinary management of this complex, multifaceted condition.

RevDate: 2025-10-23
CmpDate: 2025-10-23

Chatterjee S, Mahata J, Kateriya S, et al (2025)

Pathways in the brain, heart and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence.

Cardio-oncology (London, England), 11(1):94.

BACKGROUND: SARS-CoV-2 non-structural protein 6 (NSP6) in the host's tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Its reported role in immune evasion, viral replication and egress from the cells as well as its gain of function mutations occurring independently in various variants underscores its importance.

METHODS: Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of regulated host proteins interacting with reported SARS-CoV-2 NSP6 interacting proteins - SIGMAR1, ATP13A3, ATP5MG, and ATP6AP1. Tissue-specific protein interactomes and hub genes in these interactomes were found, and drugs targeting them were sought out.

RESULTS: Key hub genes in the brain were CCND1, CDK2, CCNA1, CDC6, CDKN1B, SKP1, CCNB1, etc., whereas in the heart were RAB7A, ATP6V0D1, LAMP2, TGFB1, CANX, LGALS3, etc. Lung hub genes were ATP6V0A1, ATP6V0A2, ATP6V0D1, ATP6V1D, ATP6V1B1, ATP6V1E1, TGFB1, EGF, TGFBR2, and LGALS3. Hub gene associated pathways in the brain were iron uptake and transport, G1/S transition, and small cell Lung cancer. Differentiation of dendritic cells and reduction of intraphagosomal pH to 5 - were prominent pathways in lung. In heart, phagosome associated pathways, and regulation of intracellular were prominent. Key therapeutic targets identified in the brain are CDK2, targeted by acetaminophen and raltitrexed; CCNE1 by palbociclib; and CCND1 by palbociclib, acetaminophen, lapatinib, doxorubicin, and methotrexate. In the heart, TGFB1 and APP are targeted by inositol, while LGALS3, upregulated after COVID-19 can be targeted by non-approved drugs (Belapectin, Olitigaltin, Lactose anhydrous, Davanat). In the lungs, TGFB1 and TGFBR2 are targeted by irinotecan, and EGF by cetuximab.

CONCLUSIONS: This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19.

RevDate: 2025-10-22
CmpDate: 2025-10-22

Guzmán Rivera J, Zheng H, Richlin B, et al (2025)

Mass spectrometry combined with machine learning identifies novel protein signatures as demonstrated with multisystem inflammatory syndrome in children.

Scientific reports, 15(1):36843.

Rapid and accurate diagnosis of emerging inflammatory illnesses is challenging due to overlapping clinical features with existing conditions. We demonstrate an approach that integrates proteomic analysis with machine learning to identify diagnostic protein signatures, using the example of SARS-CoV-2-induced multisystem inflammatory syndrome in children (MIS-C). We used plasma samples collected from subjects diagnosed with MIS-C and compared them first to controls with asymptomatic/mild SARS-CoV-2 infection and then to controls with pneumonia or Kawasaki disease. We used mass spectrometry to identify proteins and support vector machine (SVM) algorithm-based classification schemes to identify protein signatures. Diagnostic accuracy was assessed by calculating sensitivity, specificity, and area under the ROC curve (AUC), and corrected for overfitting by cross-validation. Proteomic analysis of a training dataset containing MIS-C (N = 17), and asymptomatic/mild SARS-CoV-2 infected control samples (N = 20) identified 643 proteins, of which 101 were differentially expressed. Plasma proteins associated with inflammation increased, and those associated with metabolism and coagulation decreased in MIS-C relative to controls. The SVM machine learning algorithm identified a three-protein model (ORM1, AZGP1, SERPINA3) that achieved 90.0% specificity, 88.2% sensitivity, and 93.5% AUC, distinguishing MIS-C from controls in the training set. Performance was retained in the validation dataset utilizing MIS-C (N = 19) and asymptomatic/mild SARS-CoV-2 infected control samples (N = 10) (90.0% specificity, 84.2% sensitivity, 87.4% AUC). We next replicated our approach to compare MIS-C with similarly presenting syndromes, such as pneumonia (N = 17) and Kawasaki disease (N = 13), and found a distinct three-protein signature (VWF, FCGBP, and SERPINA3) that accurately distinguished MIS-C from the other conditions (97.5% specificity, 89.5% sensitivity, 95.6% AUC). A software tool was also developed that may be used to evaluate other protein signatures using our data. These results demonstrate that the use of mass spectrometry to identify candidate plasma proteins followed by machine learning, specifically SVM, is an efficient strategy for identifying and evaluating biomarker signatures for disease classification.

RevDate: 2025-10-22
CmpDate: 2025-10-22

Ortega-Martin E, Richards-Belle A, Newlands F, et al (2025)

Children and young people with persistent post-COVID-19 condition over 24 months: a mixed-methods study.

BMJ paediatrics open, 9(1): pii:10.1136/bmjpo-2025-003634.

PURPOSE: While most children and young people (CYP) recover from COVID-19, some develop 'post-COVID-19 condition' (PCC), affecting their health and well-being. We explored (1) whether distinct persistent PCC symptom subgroups exist in CYP and whether these subgroups remain stable up to 24 months postinfection; (2) whether impairments differ across subgroups and (3) how CYP with persistent PCC describe the evolving impact of the pandemic/lockdowns on their health and experiences up to 24 months postinfection.

METHODS: A cohort of CYP across England was recruited in 2020-2021 (the children and young people with Long COVID study). A subsample of 68 CYP meeting the PCC Delphi research definition at 3, 6, 12 and 24 months post-PCR-confirmed infection was analysed. Latent class analysis identified symptom subgroups (objective 1); associations with impairments (measured via EuroQol Five Dimensions Youth) were examined (objective 2). Free-text responses from six CYP at all four follow-up points (n=24) were thematically analysed to capture evolving experiences (objective 3).

RESULTS: Included CYP were older (72.1% were 15-17 years), female (82.4%) and white (80.9%). Two symptom groups emerged: a frequent symptom subgroup (median: 6.5-9 symptoms over time, mainly shortness of breath and tiredness); and a less frequent symptom subgroup (median: 4-5 symptoms, mostly tiredness). Generally, no association was found between symptom subgroups and impairments. Qualitative analysis indicated feelings of anxiety, respiratory problems and concerns around relaxation of lockdown restrictions persisted over follow-up. School-related worries were transient.

DISCUSSION: Even CYP with persistent PCC characterised by fewer symptoms experience long-term anxiety and impact, emphasising even few symptoms can be debilitating and underscoring the need for personalised PCC management for CYP.

RevDate: 2025-10-22

Sarkanen T, Merikanto I, Bjorvatn B, et al (2025)

Long COVID as a risk factor for hypersomnolence and fatigue: insights from the 2nd International Covid Sleep Study Collaboration (ICOSS-2).

Sleep medicine, 136:106764 pii:S1389-9457(25)00439-3 [Epub ahead of print].

BACKGROUND: Hypersomnolence, defined as excessive daytime sleepiness (EDS), excessive quantity of sleep (EQS), sleep inertia, and fatigue reduce quality of life. We assessed associations of the COVID-19 pandemic, infection without long-term sequalae (short COVID, SC), and long COVID (LC) on hypersomnolence and fatigue in a large population across different countries.

METHODS: As part of an online questionnaire (ICOSS-2), we assessed EDS via the Epworth Sleepiness Scale (ESS), fatigue via Fatigue Severity Scale (FSS), and sleep duration at night and per 24 h. We also assessed the associations with EDS, sleep inertia, fatigue and napping by their frequencies, during the pandemic in COVID-negative, SC and LC participants.

RESULTS: The final cohort comprised 13,656 participants (69.1 % women, 42.7 ± 16.6 years), with 12.4 % classified SC and 7.5 % LC. ESS scores were higher in LC (9.16, 95 % CI [8.78, 9.53]) compared to SC (7.26, [6.97, 7.55]) and COVID-negative (6.53, [6.43, 6.63]). LC also had higher odds of ESS>10 (OR 1.58, [1.18,2.09]). FSS scores were higher in LC (median 51, IQR 39-59) than SC (34, 25-44) and COVID-negative (35, 25-45), with LC having 2.22 higher odds of severe fatigue. LC cases also reported more EQS (≥10/24 h) than COVID-negative. Worsening of EDS, fatigue, sleep inertia, and napping was reported during pandemic to a greater extent in LC.

CONCLUSIONS: LC was associated with higher levels of hypersomnolence and fatigue than in SC or COVID-negative participants, highlighting the need for interventions and future research focusing on sleep symptoms and their relation to long-term health outcomes.

RevDate: 2025-10-22
CmpDate: 2025-10-22

Toepffer A, Früh M, Rocktäschel T, et al (2025)

Cognition-associated gray matter volume alterations in long-COVID show sex-specific patterns.

Frontiers in psychiatry, 16:1653295.

INTRODUCTION: The long-term effects of the coronavirus disease 2019 (COVID-19) are a major concern in today's society, with cognitive impairment being an important manifestation. Notably, men and women exhibit differences in disease progression and the prevalence of long-COVID. This study aims to investigate sex differences in cognitively impaired long-COVID individuals and their potential association with alterations in gray matter volume (GMV).

METHODS: We conducted MRI at 3 Tesla to investigate brain structural correlates of cognitive impairment in long-COVID patients using voxel-based morphometry (VBM) and compared these patients to a healthy control (HC) group (n=30, female=13, male=17). Long-COVID patients underwent scanning and neuropsychiatric assessment on average 9.9 months after their acute and mostly mild COVID-19 infection. Based on Montreal Cognitive Assessment (MoCA) scores, they were classified into two groups: the PCn group, showing preserved cognitive function with MoCA scores of 26 or higher (n=36, female=23, male=13), and the PCcog group, characterized by cognitive impairment with MoCA scores below 26 (n=28, female=15, male=13). Subsequent analyses were performed separately for males and females to investigate sex-specific brain structural correlates of cognitive impairment.

RESULTS: Our analysis revealed significant GMV alterations in long-COVID patients across various brain regions, encompassing both shared and sex-specific regional changes. In females, these alterations were more restricted, affecting anterior frontal, limbic, and diencephalic regions. In males, GMV alterations were more widespread, involving neocortical regions such as the parietal, occipital, and motor cortices, and were characterized by a greater number of affected clusters.

DISCUSSION: Our findings demonstrate GMV alterations in both men and women with cognitive impairment, exhibiting sex-specific differences in affected regions. These differences suggest potentially distinct underlying mechanisms, highlighting the need for further research into their functional implications and relevance for personalized treatment strategies.

RevDate: 2025-10-22
CmpDate: 2025-10-22

He X, W Gao (2025)

Persistent pain and brain fog after COVID-19 infection in European adults aged 50 and over: a population-based longitudinal study.

BMC infectious diseases, 25(1):1366.

BACKGROUND: Psychological distress has been identified as a risk factor for long COVID in individuals infected with COVID-19. Little is known about the differences in long COVID symptom profiles between older adults with pre-existing depression and those without.

METHODS: A population-based longitudinal prospective study was performed using the Survey of Health, Ageing and Retirement in Europe (SHARE) with participants aged 50 years and older. Depression was assessed by the EURO-D scale at the baseline. Long COVID symptoms were self-reported by participants during the 12-month follow-up. A hurdle negative binomial model was employed to assess the impact of pre-existing depression on the burden of long COVID. We compared the differences in symptoms between participants with pre-existing depression and those without with the Chi-squared test.

RESULTS: Participants with pre-existing depression had an approximately 16% increased risk of experiencing additional persistent symptoms after COVID-19 infection. During the 12-month follow-up following COVID-19 infection, the prevalence of headaches (32.2% vs. 25.9%; P = 0.027), body aches or joint pain (38.5% vs. 29.4%; P < 0.001), and confusion (10.6% vs. 7.6%; P < 0.01) were significantly higher among participants with pre-existing depression than among those without.

CONCLUSION: Older adults with pre-existing depression had a higher burden of long COVID following COVID-19 infection and they were more likely to suffer from persistent physical pain and confusion compared to those without a history of depression.

RevDate: 2025-10-21
CmpDate: 2025-10-21

Dowrick A, MacLean A, Ziebland S, et al (2025)

Trust in Transition: Exploring Changing Trust in Vaccination in the Context of Long Covid in the United Kingdom.

Health expectations : an international journal of public participation in health care and health policy, 28(5):e70459.

BACKGROUND: New drugs and vaccines usually come with the promise and hope of benefit. We explore stories about the variable and sometimes disappointing effects of Covid-19 vaccines in the context of post-Covid-19 syndrome ('long Covid'), aiming to understand how people with long Covid made sense of unexpected vaccine responses and how these experiences impacted their trust in vaccination.

METHODS: We carried out 33 interviews with people who described both positive and negative unexpected vaccine experiences connected to long Covid.

RESULTS: Trust and distrust in the multiple potential roles of Covid vaccines in relation to long Covid impacted perspectives on future vaccine uptake. Some participants feared being labelled as anti-vaxx if they discussed unexpected vaccine impacts. Disengagement by healthcare professionals in discussions about the possibility of individual vaccine harms had the inverse consequence of limiting uptake of further Covid vaccines. Distrust could also grow in relation to unrealised benefits of vaccination-in this case, the official role as protection from severe infection and the unofficial role of treatment. Participants who trusted vaccines as a form of treatment struggled to access them for this use.

CONCLUSION: The gap between scientific discourse-which recognised potential benefits and potential harms of vaccines in relation to long Covid-and public health discourse, which tended to focus on protection from infection, contributed to difficulties in maintaining trust after unexpected vaccine experiences. Further research to better characterise who is likely to benefit from vaccination and who might be at risk of worsening long Covid symptoms would enable better conversations between patients and healthcare professionals when making decisions about further vaccination.

The study was guided by a patient and public involvement and engagement (PPIE) group from project development through to dissemination. People with long Covid supported recruitment strategies, informed the development of topic guides, reviewed findings and offered suggestions for dissemination. Study participants were also invited to review and feedback on findings.

RevDate: 2025-10-21

Oba S, Hosoya T, Iwai H, et al (2025)

Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.

Immunological medicine [Epub ahead of print].

Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.

RevDate: 2025-10-20

Oh J, Kim S, Jo H, et al (2025)

Burden of post-acute sequelae of COVID-19 in patients with type 2 diabetes: a binational cohort study in South Korea and Japan.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases pii:S1201-9712(25)00365-0 [Epub ahead of print].

BACKGROUND: The long-term sequelae of COVID-19 remain a growing concern; however, a limited study targeting individuals with preexisting type 2 diabetes mellitus (T2DM) and Asian populations has been conducted. This large-scale, binational cohort study with extended follow-up aimed to evaluate the risk of post-acute sequelae of COVID-19 across multiple organ systems in individuals with T2DM.

METHODS: This study used binational, population-based cohorts in South Korea (K-COV-N; discovery cohort; n=3,002,271) and Japan (JMDC; validation cohort; n=1,125,045). All individuals aged >19 years were included from January 1, 2020, to December 31, 2022. We estimated the long-term risk of post-acute sequelae following SARS-CoV-2 infection. We defined the primary outcome as the onset of 65 diseases across 9 organ systems beyond the first 30 days after SARS-CoV-2 infection. After applying propensity score-based overlap weighting, we utilized Cox proportional hazards models to estimate adjusted hazard ratios (HRs) with 95% CIs for post-acute sequelae of COVID-19 within the weighted population. We further examined how the risk of sequelae changed over time following COVID-19 diagnosis. We also conducted multiple subgroup analyses on the severity of COVID-19, COVID-19 vaccination status, and T2DM-related complications.

RESULTS: In the overlap-weighted discovery cohort, 1,056,277 individuals with preexisting T2DM were analyzed (mean age: 58.06 years [SD, 10.02]; 39.41% females). Compared with non-infected individuals, those with SARS-CoV-2 infection showed an increased long-term risk of sequelae across eight organ systems, including cardiovascular diseases (aHR, 1.11 [95% CI, 1.09-1.13]), dermatologic conditions (aHR, 1.20 [1.10-1.31]), endocrine disorders (aHR, 1.04 [1.01-1.08]), gastrointestinal diseases (aHR, 1.11 [1.07-1.14]), hepato-biliary-pancreatic disorders (aHR, 1.07 [1.03-1.11]), kidney disorders (aHR, 1.09 [1.03-1.16]), neurological disorders (aHR, 1.11 [1.03-1.20]), and pulmonary diseases (aHR, 1.11 [1.04-1.18]). Specifically, of 65 diseases, 45 showed a significantly elevated incident risk following a COVID-19 diagnosis. The risk of sequelae was higher in individuals with moderate-to-severe COVID-19 and persisted up to 12 months post-infection, with attenuation thereafter. COVID-19 vaccination was associated with reduced sequelae risk of developing some sequelae; however, the risk was still generally higher than in non-infected individuals. Similar trends were observed in the validation cohort, where all 65 specific diseases showed significant associations with long-term sequelae.

CONCLUSION: Among individuals with preexisting T2DM, SARS-CoV-2 infection was associated with an increased risk of long-term sequelae across multiple organ systems, particularly in moderate-to-severe cases. Risks peaked within 12 months and gradually subsided thereafter, highlighting the enduring impact of COVID-19 and the need for sustained monitoring and preventive care in this high-risk population.

RevDate: 2025-10-20

Bassi A, Devasenapathy N, Thankachen SS, et al (2025)

Effectiveness of Colchicine for the Treatment of Long COVID: A Randomized Clinical Trial.

JAMA internal medicine pii:2840468 [Epub ahead of print].

IMPORTANCE: Long COVID is characterized by persistent symptoms after SARS-CoV-2 infection, with inflammation playing a key role in pathogenesis. Colchicine, an established anti-inflammatory agent, may reduce these symptoms by targeting inflammatory pathways.

OBJECTIVE: To evaluate the superiority of colchicine over placebo in improving functional outcome at 52 weeks from baseline.

This double-blind, 1:1 randomized clinical trial recruited participants with confirmed SARS-CoV-2 infection and persistent symptoms from 8 hospitals in 6 states in India between January 2022 and July 2023. Individuals were eligible if they had functional limitation (Post-COVID-19 Functional Status scale grade 2 or more) and/or elevated inflammatory markers (high-sensitivity C-reactive protein >0.20 mg/dL and/or neutrophil to lymphocyte ratio >5). Outcomes were assessed at 12, 26, and 52 weeks after randomization. Data were analyzed from January to February 2025.

INTERVENTIONS: Participants were randomly assigned to receive colchicine, 0.5 mg, once or twice daily, based on body weight, or placebo for 26 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was the change in distance walked during a 6-minute walk test from baseline to 52 weeks. Secondary outcomes included changes in inflammatory markers and patient-reported outcome measures, such as quality of life, anxiety, depression, fatigue, dyspnea, measured using validated instruments.

RESULTS: Of 346 participants included in the modified intention-to-treat analysis, 209 (60.4%) were female, 137 (39.6%) were male, and the mean (SD) age was 46 (12) years. At 52 weeks, there was no difference in mean (SD) change in 6-minute walk test distance between the colchicine and placebo groups (colchicine, 35.5 [19.76] m; placebo, 29.96 [19.83] m; mean difference, 5.59 m; 95% CI, -9.00 to 20.18; P = .45). Similar null findings were seen across all predefined outcomes, except for a small, nonclinically relevant difference in the mean (SD) ratio of forced expiratory volume in 1 second to forced vital capacity (colchicine, -0.02 [0.03]; placebo, -0.06 [0.03]; mean difference, 0.04; 95% CI, 0.02 to 0.07; P = .001).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among adults with long COVID, colchicine did not improve functional capacity, respiratory function, or inflammatory markers. These findings underscore the need to explore alternative therapeutic approaches for long COVID.

TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2021/11/038234.

RevDate: 2025-10-20
CmpDate: 2025-10-20

Raineri A, Rueegg S, Zimmermann P, et al (2025)

Long COVID in children and adolescents: results from three cross-sectional school-based cohorts with adjudication.

Swiss medical weekly, 155:4337 pii:4337.

STUDY AIMS: The prevalence of Long COVID in children and adolescents is heterogeneous, ranging from 1% to 51%, depending on the population studied. The lack of a standardised approach for establishing a Long COVID diagnosis in children and adolescents complicates the accurate assessment of prevalence, risk factors and outcomes. The present study aimed to examine the value of standardised interviews and an adjudication process to better understand self- or proxy-reported symptoms lasting longer than 12 weeks compatible with Long COVID in children and adolescents during the COVID-19 pandemic.

METHODS: We conducted a school-based, prospective cohort study (Ciao Corona) from March 2020 to July 2022 in the Canton of Zurich, Switzerland. Of 156 invited schools, 55 agreed to participate. Primary schools were randomly selected across all 12 districts of the Canton of Zurich, with nearby secondary schools subsequently invited. Within participating schools, classes were randomly selected, stratified by school level, and all students aged 6-17 years in selected classes were eligible. At three different time points (March/April 2021, November/December 2021 and June/July 2022), school-aged children and adolescents underwent serology testing and completed online questionnaires, including questions on symptoms lasting ≥12 weeks compatible with Long COVID. We invited those with persisting symptoms and who were seropositive for SARS-CoV-2 - whether "infected" i.e. infection and no vaccination or having "hybrid immunity" i.e. infection and vaccination - to participate in interviews to allow us to better understand the pattern, severity and timing of the reported symptoms. An adjudication process with experts then followed to assess the probability of Long COVID.

RESULTS: 39/1120 (3.5%) seropositive children and adolescents (i.e. infected or with hybrid immunity) reported persisting symptoms (≥12 weeks). The most frequently reported symptoms were headache, tiredness and stomach ache. In 20/39 (51%) with persisting symptoms who agreed to be interviewed, the adjudication committee concluded that Long COVID was unlikely in 13 (65%), possible in 7 (35%) and likely in 0 participants.

CONCLUSIONS: Relying exclusively on self- or proxy-reported questionnaire data, without more detailed information may overestimate Long COVID in children and adolescents. Implementing standardised interviews and an adjudication process helps to contextualise self- or proxy-reported symptoms compatible with Long COVID.

TRIAL REGISTRATION:  https://clinicaltrials.gov NCT04448717.

RevDate: 2025-10-20
CmpDate: 2025-10-20

Rossi N, Benítez-Cruz J, Marín-García P, et al (2025)

Post-COVID syndrome patients show reduced anti-Spike antibodies compared to COVID-recovered controls, but enhanced IgG4/IgG1 switch after the third vaccine dose.

Frontiers in immunology, 16:1670324.

INTRODUCTION: Long COVID and post-COVID syndromes represent a significant global health crisis and a substantial societal challenge. Although an altered immunological response has been suggested as a possible underlying mechanism, the antibody response to vaccination and infection of the patients remains unclear.

METHODS: We studied a post-COVID syndrome cohort compared to a COVID-recovered cohort. Initially, we established the risk factors and the evolution of symptoms. Then, we analyzed the antibody response, focusing on immunoglobulin subclasses. Apart from determining immunoglobulin G (IgG) against the Nucleocapsid, which is a marker of infection, we analyzed IgG and its subclasses against the full-length Spike, and against the receptor-binding domain (RBD). Additionally, we examined the switch to IgG4, which can be promoted by repeated antigen exposure.

RESULTS: We show the major risk factors for developing post-COVID syndrome, such as infection before vaccination and comorbidities. Furthermore, we describe the evolution of the post-COVID symptoms, which agrees with previous reports. Regarding the antibody response, we found that compared to COVID-recovered individuals, post-COVID patients present readily detectable anti-Nucleocapsid IgG but low quantities of anti-Spike antibodies. Nevertheless, the anti-RBD IgG1 levels are similar between post-COVID and COVID samples. Interestingly, post-COVID patients with three vaccine doses, who were infected before vaccination by the Wuhan strain and subsequently reinfected post-Omicron, show decreased Spike response but intensified anti-RBD IgG4/IgG1 switch, compared to their non-reinfected post-COVID counterparts.

DISCUSSION: Our results support a differential antibody response in post-COVID versus COVID-recovered patients, which might be relevant for post-COVID syndrome treatment, including appropriate recall vaccination strategies for the still-circulating SARS-CoV-2.

RevDate: 2025-10-20
CmpDate: 2025-10-20

Iftekhar N, Wilson A, Nguty L, et al (2025)

Normative data for the 10-min lean test in adults without orthostatic intolerance.

Frontiers in neurology, 16:1625216.

BACKGROUND: Orthostatic intolerance syndromes such as Orthostatic Hypotension (OH) and Postural Orthostatic Tachycardia Syndrome (PoTS) are common symptoms seen in post-infection conditions and other neurological conditions with autonomic dysfunction. The 10-min Lean Test (LT) is an objective clinical test used to assess these symptoms and direct management. There is, however, no robust literature on normative data for this test, particularly from a younger population.

AIMS: The aim of this study was to produce a healthy control data set for LT, which can be used for comparison with the patient population with health conditions.

METHODS: Individuals recruited into the study had no history or symptoms of orthostatic intolerance; autonomic dysfunction; post-infection conditions (such as long COVID); or other neurological conditions with hemodynamic instability. Participants were primarily recruited from the general population in a metropolitan city. All participants underwent a standardized LT. Lying Blood Pressure (BP) and Heart Rate (HR) after 2 min of lying down supine was recorded, followed by BP and HR recordings at every minute of standing (leaning against a wall) up to 10 min, along with recording subject-reported symptoms at each time point.

RESULTS: A complete dataset was available for 112 individuals (60.7% Female, 39.3% Male). The population was 61.6% Caucasian, 8.0% Asian, 3.6% Black/Caribbean, 9.8% Mixed, and 17.0% Other; the mean age was 35.3 ± 15.1, with a BMI of 24.8 ± 4.0; 30.6% of individuals had a background medical condition, but none of the exclusion criteria. During LT, upon standing, the average change of HR was an increase of 9.89 ± 8.15 bpm. The sustained HR increase (HR increase sustained at two consecutive readings) was an average of 6.23 ± 6.94 bpm. The predominant response with BP was an increase of systolic BP, with the average initial increase being 7.55 ± 10.88 mmHg. None of the participants met the diagnostic criteria for symptomatic OH or PoTS during LT.

CONCLUSION: For the first time in the current literature, 10-min LT data from a relatively younger population without orthostatic intolerance have been gathered. This normative data will help interpret LT findings in younger patients with orthostatic Intolerance better and be useful in managing dysautonomia in specific conditions.

RevDate: 2025-10-20
CmpDate: 2025-10-20

Bouchari A, Dami F, El Hammouti M, et al (2025)

Long-Term Outcomes of Chronic Hemodialysis Patients Following SARS-CoV-2 Infection.

Cureus, 17(9):e92535.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on patients undergoing chronic hemodialysis (CHD). Several studies have explored the long-term outcomes of CHD patients who recovered from SARS-CoV-2 infection. This study aims to identify the factors associated with persistent symptoms (long COVID) among CHD patients.

METHODS: We conducted a multicenter, descriptive, and analytical cohort study across nine hemodialysis centers (public, private, and nonprofit) in the city of Tangier. Data were collected through interviews with patients and a review of their medical records. Statistical analysis was performed using IBM SPSS Statistics version 25.

RESULTS: Among 945 CHD patients, 163 had a documented SARS-CoV-2 infection, with a median age of 55 years (interquartile range (IQR): 43-67). The most frequently reported post-infection symptoms were fatigue (62%), anxiety (53%), arthralgia (40%), cough (33%), weight loss (29%), sleep perturbations (28%), anosmia (30%), dyspnea (25%), anorexia (24%), dysgeusia (18%), and concentration difficulties (16%). After adjusting for diabetes, obesity, oxygen therapy, hospitalization, and use of hydroxychloroquine or corticosteroids, diabetes emerged as the main factor for long COVID (OR = 3.8; 95% CI (1.5-9.6); p = 0.004). Fatigue was significantly associated with diabetes (OR = 2.9; 95% CI (1.3-6.5); p = 0.01) and female gender (OR = 2.1; 95% CI (1.02-4.2); p = 0.04). Anxiety was linked to diabetes (OR = 2.6; 95% CI (1.2-5.5); p = 0.01) and obesity (OR = 2.5; 95% CI (1.01-6.4); p = 0.04). Dyspnea was associated with obesity (OR = 4.0; 95% CI (1.4-10.4); p = 0.004).

CONCLUSION: Our study highlights the substantial prevalence of persistent post-COVID-19 symptoms among CHD patients. The findings emphasize the necessity of individualized long-term care in this high-risk group.

RevDate: 2025-10-18

Bousquet C, Pereda-Loth V, Pierron D, et al (2025)

Self-reported cognitive and affective complaints associated with olfactory loss in an online survey of individuals with COVID-19.

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery [Epub ahead of print].

PURPOSE: The symptomatology associated with COVID-19 is very diverse, ranging from flu-like symptoms to those affecting olfaction, cognition or mood for long periods. The present study explored the associations between self-reported olfactory deficits and cognitive and emotional complaints in a large-scale online survey conducted among individuals who had COVID-19.

METHODS: Two complementary online studies were set up, one in France and the other in Mexico, involving 3108 and 364 volunteers respectively, to investigate the link between olfactory loss in COVID-19 and self-reported cognitive and emotional changes. Cognitive and affective complaints were assessed using simple yes/no items inspired by previously published studies, but not based on standardized clinical questionnaires.

RESULTS: A first result was that cognitive difficulties are more frequent in COVID-19 individuals with long-standing olfactory disorders than in patients who have recently developed olfactory disorders. In addition, we also showed that the prevalence of cognitive difficulties is higher in COVID-19 patients with olfactory disorders than in those without. Furthermore, cognitive difficulties in patients with long-term olfactory disorders are more strongly associated with memory difficulties than with attention difficulties. Finally, mood disorders were more frequent in COVID-19 participants with olfactory loss than in those without.

CONCLUSION: Taken together, these data suggest that in COVID-19, the duration of olfactory loss is a key factor, strongly associated with cognitive and affective impairment. These data should provide us with further guidance on the management of people affected, which should not simply be unimodal, targeting just one category of symptoms.

RevDate: 2025-10-18

Sharma D, Kamm CP, Hoepner R, et al (2025)

Characterizing post-COVID-19 syndrome in multiple sclerosis: Vaccine status, infection burden, and therapy categories as predictors.

Multiple sclerosis and related disorders, 104:106792 pii:S2211-0348(25)00534-6 [Epub ahead of print].

BACKGROUND: Post-COVID-19 syndrome (PCS) is a significant long-term complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, yet its prevalence and risk factors in people with multiple sclerosis (pwMS) under disease-modifying therapies (DMTs) remain underexplored.

OBJECTIVE: This study aimed to characterize the clinical course of coronavirus disease 2019 (COVID-19) and identify predictors of PCS in pwMS, focusing on vaccination status, infection severity and frequency, and DMT categories.

METHODS: In this cross-sectional study, 107 pwMS from two centers completed a survey assessing COVID-19 history, persistent symptoms, immunotherapy, and vaccination status. PCS was defined as symptoms persisting >12 weeks after infection. Participants were stratified by DMT categories, infection number, and vaccination status.

RESULTS: Of 107 participants, 7 (6.5 %) reported PCS. The most frequent symptoms were fatigue (71.4 %), pain (57.1 %), and headache (42.9 %). Patients with PCS had a higher mean number of SARS-CoV-2 infections (2.1, 95 % CI: 1.3-3.0) compared to those without (1.3, 95 % CI: 1.2-1.4; p = 0.004). A significant association was found with DMT category: 71.4 % (5/7) of affected individuals were on category I therapies (Interferon/Glatiramer acetate, Dimethyl fumarate, Teriflunomide) compared to 17 % of pwMS without PCS (p < 0.001). No significant effect was observed for COVID-19 severity or vaccination status.

CONCLUSIONS: PCS prevalence in this MS cohort was lower than in the general population, but category I DMTs and repeated infections were key risk factors. Findings suggest the need for individualized risk assessment, indicating that higher efficacy DMTs do not appear to pose an increased risk of PCS in pwMS.

RevDate: 2025-10-18

Akbar N, Phadke S, Mehelay S, et al (2025)

Considerations of race and ethnicity within rehabilitation studies for post COVID-19 condition: A scoping review.

PM & R : the journal of injury, function, and rehabilitation [Epub ahead of print].

Post COVID-19 condition (PCC) or long COVID disproportionately affects racial and ethnic minority communities. There are a growing number of rehabilitation studies for PCC, however, it has yet to be determined whether existing studies take race and ethnicity into account in their study designs and whether existing rehabilitative approaches are equally effective across diverse racial and ethnic groups. The objective of this study was to describe the extent to which rehabilitation studies of PCC consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, designing intervention delivery and adherence promoting approaches, selecting outcome measures, and reporting results. Of the 4845 studies screened, 23 met eligibility criteria and were included in this review. The most common reason for exclusion was a lack of mention of race or ethnicity anywhere within the article. Among the 23 studies included, 13 studies provided data on the race and/or ethnicity characteristics of their sample, with 88% of participants across all of these studies being White. Less than 25% of studies described the incorporation of race and/or ethnicity in their recruitment strategies (n = 3, 13%) or data analysis (n = 5, 22%). Greater racial and ethnic diversity is needed within rehabilitation studies for PCC as there is currently a significant underrepresentation of racial and ethnic minorities in existing studies. Overall, more PCC rehabilitation studies need to incorporate race and ethnicity into their study designs as it is not well understood whether existing rehabilitation strategies are equally effective across different racial and ethnic groups.

RevDate: 2025-10-17

Rutsch M, R Deck (2025)

[Work-related participation restrictions of Long COVID rehabilitants over time - Findings of a qualitative study].

Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen pii:S1865-9217(25)00200-4 [Epub ahead of print].

BACKGROUND: People who are affected by long COVID (LC) and have limitations in their ability to work can apply for a multi-professional rehabilitation programme. This qualitative study analysed the development of occupational participation, health limitations at work and factors supporting occupational participation in LC rehabilitants.

METHODS: Guided telephone interviews were conducted with LC rehabilitants aged 18-65 years, who were undergoing pneumological rehabilitation, at three time points (shortly after the end of rehabilitation, and six and twelve months after rehabilitation). Data were analysed using qualitative content analysis according to Mayring.

RESULTS: Between 04/2021 and 07/2022, a total of 30 interviews were conducted with 11 rehabilitants (N = 7 women; average age: 50 years). Three health-related stress dimensions were identified: cognitive (e. g., word-finding difficulties, concentration problems), psychosocial (e. g., anxiety, worry), and physical (e. g., physical exhaustion, shortness of breath) limitations. The reintegration prepared by social services, the general conditions at the workplace (e. g., flexible working hours, empathy in the workplace) and personality traits, such as acceptance of personal limitations, were described as conducive to occupational participation. Respondents used compensatory techniques (e. g., creating mnemonics) and pacing to cope with the demands of work despite existing limitations.

CONCLUSION: The results of the study show that "returning to work" is not the same as "regaining the ability to work". In both rehabilitation and aftercare, the restoration of physical, psychosocial, and cognitive work ability should play an essential role in counteracting the manifestation of participation restrictions.

RevDate: 2025-10-17
CmpDate: 2025-10-17

McLoughlin C, Wang JY, Do F, et al (2025)

An Exploration of How Functional Neurological Disorder Is Discussed on X (Twitter): Mixed Methods Study Using Social Network and Content Analysis.

Journal of medical Internet research, 27:e73439 pii:v27i1e73439.

BACKGROUND: Functional neurological disorder (FND) is one of the commonest conditions in neurological practice, describing symptoms like paralysis and seizures that can be severe and disabling. It is a diagnosis that is confirmed clinically rather than by scans or laboratory results. It is a stigmatized and widely misperceived condition, and since the emergence of long COVID, there has been some conflation of FND with other conditions, which has caused further misunderstanding. Social media has become increasingly popular for patients to learn and interact about their conditions, and the information that they seek and receive may be shaped by many factors. Prior to this study, the online discourse about FND had not been described in the literature.

OBJECTIVE: We aimed to analyze and describe how FND is discussed on the social media platform X (formerly known as Twitter) using a mixed methods approach.

METHODS: Using search terms related to FND, the authors collected data from 426 users and 1104 posts, generating a total of 7640 replies and reposts over a 2-month time frame in 2024. Quantitative descriptive and social network analyses were carried out to map key influential users and communities, in addition to measuring the influence of users. Content analysis was undertaken to describe the prevalent topics being discussed.

RESULTS: More users overall associated with conditions outside FND (n=180, 42.3%), mostly long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, compared with FND (n=148, 34.7%). Self-declared patients made up 40.8% (450/1104) of posts and 36.4% (n=155) of users. Social network analysis revealed 2 separate communities with little interaction. There was a prominence of myalgic encephalomyelitis/chronic fatigue syndrome and long COVID-associated users (nodes) over FND users (nodes). The former cluster showed stronger connections outwardly or peripherally than the FND cluster, suggesting that they may have a stronger impact on shaping the public narrative around FND than FND nodes. In total, 7 of the top 10 most influential users often displayed anti-FND views, while FND organizations and professionals had much less influence. There were 58 posts with at least 5000 views. Of these 58, 10 were from self-declared FND professionals, while 19 were from self-declared professionals associated with other conditions. Of these highly viewed posts, 38 of 58 were negatively predisposed toward FND. Content analysis showed themes of (1) conflict, (2) deception, (3) mistreatment and harm, (4) symptom experience, (5) knowledge, and (6) support.

CONCLUSIONS: A large proportion of the discourse around FND on X is shaped by users who are dismissive of the concept of FND and those associated with it. These findings have implications for individuals getting support for a condition that is already widely misunderstood. This study could provide a template for assessing how other stigmatized conditions are perceived on the web.

RevDate: 2025-10-17
CmpDate: 2025-10-17

Catalfamo CJ, Jacobs ET, Falk LP, et al (2025)

Concordance between self-reported SARS-CoV-2 positivity and laboratory-confirmed positivity.

PloS one, 20(10):e0334102 pii:PONE-D-24-40491.

As the use and availability of at-home antigen tests for SARS-CoV-2 infection have increased, the number of individuals with SARS-CoV-2 infections that are reported to state COVID-19 surveillance systems have decreased. Self-reported infection dates are critical to accurately track incidence and outbreaks of COVID-19 and for continued research on illness progression; however, the reliability of self-reported infection dates is unknown to date. To assess accuracy of self-reported test dates, we utilized self-reported SARS-CoV-2 testing data from the Arizona CoVHORT Study (CoVHORT) and laboratory-confirmed testing data collected by the Arizona Department of Health Services (ADHS) and calculated the difference in days between dates to examine their percent agreement. We used logistic regression to assess if any participant characteristics were associated with self-reporting a test date >7 days different than the laboratory confirmed date. A total of 1,900 CoVHORT participants aged 18 years or older were included in our analyses. Most participants (82.5%) reported a test date within 7 days of the laboratory confirmed date of their illness. Increasing age and number of weeks between testing positive and self-reporting the test date were both significantly associated with a difference of 7 days or greater between dates. There was an 84% increase (OR=1.84, 95% CI = 1.11-3.06) in likelihood of inaccurately self-reporting their SARS-CoV-2 test date for participants aged 55 years and older and a 2% increase (OR=1.02, 95% CI = 1.02-1.03) for each elapsed week following their SARS-CoV-2 test. We observed an 82% percent agreement (dates within 7 days of each other) between self-reported and laboratory confirmed test dates, suggesting that self-reported SARS-CoV-2 test dates are sufficient for identifying and tracking Long COVID or Post-COVID Conditions when a laboratory-confirmed test date is not available. However, increasing age and greater time between test date and date of self-report were found to decrease the agreement between self-reported and laboratory confirmed test dates.

RevDate: 2025-10-17
CmpDate: 2025-10-17

Luo S, Lai LY, Zhu R, et al (2025)

Prevalence and duration of common symptoms in people with long COVID: a systematic review and meta-analysis.

Journal of global health, 15:04282.

BACKGROUND: During the COVID-19 pandemic, an increasing number of patients have reported persistent symptoms after recovery, a phenomenon known as long COVID. These symptoms may persist for weeks or months, affecting the patient's daily life and health. To systematically understand the long-term impact of long COVID, this study conducted a systematic review and meta-analysis. This study aims to determine the long-term effects of long COVID by identifying, evaluating and summarising the incidence and duration of persistent symptoms after the acute phase of COVID-19.

METHOD: We searched PubMed, Embase, and medRxiv up to August 2021 for articles and preprints presenting original research on the symptoms of long COVID. Following title/abstract and full-text screening, based on the PICOS framework, we excluded articles that did not clearly report on diagnoses, reported on symptoms lasting less than four weeks, lacked epidemiological data, or did not provide complete data. We assessed the bias of included studies using the Newcastle-Ottawa Scale. For effects reported in more than two studies, we performed meta-analysis of prevalence, and also counted the duration of each symptom.

RESULTS: We included 19 observational studies in the meta-analysis, through which we determined the incidence and duration of five common long COVID symptoms, including cognitive/memory/attention disorders (36%, unreported duration), fatigue (34%, 5.5 months), mental health problems (including anxiety and depression, 31%, 3.5-3.8 months), and dyspnoea (24%, 6.52 months) and chest pain (23%, 2 months).

CONCLUSIONS: The symptoms of long COVID usually persist after the acute phase of COVID-19. The clustering of long COVID symptoms provides a direction for studying the aetiology, diagnosis, and management of post-COVID conditions. Our findings provide important baseline data for the prevention and treatment of long COVID.

RevDate: 2025-10-16

January J, Zwaenepoel O, Sanga N, et al (2025)

High sensitivity perovskite-tagged nanobody electrochemiluminescent immunosensor for spike (S1) protein biomarker-based persistent viral reservoir detection.

Bioelectrochemistry (Amsterdam, Netherlands), 168:109137 pii:S1567-5394(25)00240-3 [Epub ahead of print].

Persistent viral reservoirs (PVR) of SARS-CoV-2 (or long COVID-19) and latent COVID-19 disease have been of great concern to clinicians. Several studies have identified spike protein (S1) as a definitive biomarker for the early detection of persistent viral reservoirs and latent COVID-19. A novel sandwich-format electrochemical immunosensor integrating a nanocomposite material was engineered for rapid and sensitive latent COVID-19 detection. The platform structure, AuSPE||strep|Nb1|BSA|biotin|S1|strep-LiSmZrO3-Nb2 + BSA (AuSPE = gold screen-printed electrode, strep = streptavidin-thiol, Nb1 = primary nanobody, Nb2 = secondary nanobody, BSA = bovine serum albumin, and spike (S1) protein = S1), featured a disposable AuSPE modified with strep to anchor a biotinylated camelid Nb1 specific to the spike protein. A Nb2 conjugated to streptavidin-labelled LiSmZrO3 perovskite completed the sandwich complex, enhancing both affinity and signal transduction. Electrochemical responses of the sensor were studied via electrochemiluminescent (ECL) signal transduction. The S1-sensitive sandwich immunosensor had a detection range of 0-1000 pg mL[-1] with a limit of detection of 0.04 pg mL[-1] via ECL. As feasibility studies, commercial spike protein in buffered solutions and human serum, highlighting the potential for the immunosensor to be used in SARS-CoV-2 patients and PVRs. The nanobody sandwich immunosensor showed excellent stability, selectivity, sensitivity, and reproducibility. The immunosensor serves as a broad PVR for a SARS-CoV-2 screening tool, detecting elevated S1 levels to enable early, targeted diagnostics.

RevDate: 2025-10-16

Adebisi YA, Ogunkola IO, Jimoh ND, et al (2025)

Tobacco smoking and the risk of Long COVID: a prospective cohort study with mediation analysis.

Journal of epidemiology and population health, 73(5):203142 pii:S2950-4333(25)00336-2 [Epub ahead of print].

BACKGROUND: Tobacco smoking is a well-established risk factor for severe acute COVID-19 outcomes, but evidence regarding its role in Long COVID is limited and inconsistent. This study investigated whether pre-pandemic smoking independently predicted Long COVID and assessed mediation by long-standing illness or disability in a nationally representative cohort.

METHODS: We analysed data from Waves 10 (2018-19) and 14 (2022-23) of the UK Household Longitudinal Study. Smoking status (current vs non-smoker) and covariates (age, sex, education, income satisfaction, ethnicity, rural/urban residence) were measured at baseline (Wave 10). Long COVID, defined as symptoms lasting ≥12 weeks following initial COVID-19 infection, was assessed at follow-up (Wave 14). Logistic regression was used to estimate the total association between smoking and Long COVID. We then applied generalized structural equation modelling and parametric causal mediation analysis, specifying long-standing illness or disability at baseline as the mediator.

RESULTS: Among 11,944 participants, 1097 (9.2 %) reported Long COVID symptoms at follow-up. In the unadjusted model, smoking was associated with increased odds of Long COVID (odds ratio [OR] = 1.22, 95 % CI: 1.00-1.48, p = 0.05), although this was only borderline significant. After adjusting for demographic and socioeconomic factors, the association was no longer statistically significant (adjusted OR = 1.11, 95 % CI: 0.91-1.35, p = 0.32). The structural equation model indicated that smoking was associated with higher likelihood of long-standing illness or disability at baseline (β = 0.461, 95 % CI: 0.33-0.59, p <0.001, log-odds scale), which in turn predicted Long COVID (β = 0.435, 95 % CI: 0.30-0.57, p <0.001, log-odds scale). Mediation analysis revealed a small but statistically significant indirect effect of smoking on Long COVID operating through long-standing illness or disability (risk difference = 0.0057, 95 % CI: 0.0020-0.0095, p = 0.003), but no significant direct effect (risk difference = 0.0027, 95 % CI: -0.0144 to 0.0199, p = 0.76).

CONCLUSION: Smoking did not independently predict Long COVID, but may increase vulnerability indirectly through pre-existing long-standing illness or disability.

RevDate: 2025-10-16

Chate RC, Carvalho CRR, Sawamura MVY, et al (2025)

Quantitative Chest Computed Tomography and Machine Learning for Subphenotyping Small Airways Disease in Long COVID.

Journal of thoracic imaging pii:00005382-990000000-00196 [Epub ahead of print].

PURPOSE: To investigate imaging phenotypes in posthospitalized COVID-19 patients by integrating quantitative CT (QCT) and machine learning (ML), with a focus on small airway disease (SAD) and its correlation with plethysmography.

MATERIALS AND METHODS: In this single-center cross-sectional retrospective study, a subanalysis of a larger prospective cohort, 257 adult survivors from the initial COVID-19 peak (mean age, 56±13 y; 49% male) were evaluated. Patients were admitted to a quaternary hospital between March 30 and August 31, 2020 (median length of stay: 16 [8-26] d) and underwent plethysmography along with volumetric inspiratory and expiratory chest CT 6 to 12 months after hospitalization. QCT parameters were derived using AI-Rad Companion Chest CT (Siemens Healthineers).

RESULTS: Hierarchical clustering of QCT parameters identified 4 phenotypes among survivors, named "SAD," "intermediate," "younger fibrotic," and "older fibrotic," based on clinical and imaging characteristics. The SAD cluster (n=37, 14%) showed higher residual volume (RV) and RV/total lung capacity (TLC) ratios as well as lower FEF25-75/forced vital capacity (FVC) on plethysmography. The older fibrotic cluster (n=42, 16%) had the lowest TLC and FVC values. The younger fibrotic cluster (n=79, 31%) demonstrated lower RV and RV/TLC ratios and higher FEF25-75 than the other phenotypes. The intermediate cluster (n=99, 39%) exhibited characteristics that were intermediate between those of SAD and fibrotic phenotypes.

CONCLUSION: The integration of inspiratory and expiratory chest CT with quantitative analysis and ML enables the identification of distinct imaging phenotypes in long COVID patients, including a unique SAD cluster strongly associated with specific pulmonary function abnormalities.

RevDate: 2025-10-16

Afrin F, Zhang Q, Alturaiki W, et al (2025)

Editorial: Advances in understanding mucosal immunity in coronaviruses: from mechanisms to vaccines.

Frontiers in immunology, 16:1702286.

RevDate: 2025-10-16

Lesgards JF, Cerdan D, C Perronne (2025)

Correction: Lesgards et al. Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways? Int. J. Mol. Sci. 2025, 26, 7879.

International journal of molecular sciences, 26(19): pii:ijms26199513.

In the original publication [...].

RevDate: 2025-10-16
CmpDate: 2025-10-16

László N, Mărginean C, Mátyás BB, et al (2025)

Macrophage Migration Inhibitory Factor and Post-Discharge Inflammatory Profiles in Severe COVID-19: A Prospective Observational Study from Romania.

International journal of molecular sciences, 26(19): pii:ijms26199697.

Dysregulated cytokine responses are a hallmark of severe COVID-19; however, the persistence of these responses following hospital discharge remains inadequately understood. This study aimed to characterize the inflammatory profile of hospitalized COVID-19 patients in Mureș County, Romania, at the point of admission and one month post-discharge. We conducted a prospective observational study involving 68 patients with RT-PCR-confirmed SARS-CoV-2 infection, classified according to disease severity. Blood samples were collected at baseline and after one month. Macrophage migration inhibitory factor (MIF) levels were quantified using ELISA, while other cytokines, including MCP-1, IP-10, IFN-γ, IL-4, IL-10, IL-13, IL-17, and TNF-α, were measured via Luminex multiplex assays. Patients with severe disease exhibited significantly elevated levels of MIF, IFN-γ, IL-17, and TNF-α at admission (p < 0.0001). Although cytokine concentrations generally declined over time, patients with severe disease continued to display persistently elevated MIF (mean 31,035 pg/mL), IFN-γ, and TNF-α, indicative of ongoing inflammatory processes. Clinical parameters such as respiratory rate and oxygen saturation correlated with disease severity. These findings suggest that severe COVID-19 induces a prolonged inflammatory response, with MIF and IFN-γ remaining elevated beyond the acute phase. Cytokine profiling holds potential for improving prognostic assessments and identifying patients at risk of long-term immune dysregulation, with MIF emerging as a potential candidate marker for immune recovery and a possible target for therapy.

RevDate: 2025-10-16
CmpDate: 2025-10-16

Zhou LM, Duncan EH, Boelig RC, et al (2025)

Whole-Blood Cellular Responses: A Promising Indicator of SARS-CoV-2 Immunity Compared to Serology.

Journal of clinical medicine, 14(19): pii:jcm14196889.

Background: Currently available immunological tests for SARS-CoV-2 assess only antibody responses. Despite the growing evidence that T cells play a crucial role in protection, especially against emerging viral variants, no routine test is available to determine T cell immunity. The prognostic value of SARS-CoV-2-specific antibodies for determining whether individuals are immune and protected against disease remains uncertain. This is in part due to the following: (a) specificity and limitations such as the sensitivity of antibody tests, and (b) the lack of correlation between antibody titers (quantity) and the antiviral function of antibodies (quality). Approximately a quarter of SARS-CoV-2-infected patients with symptoms fail to show seroconversion in serological assays. Methods: The current report describes the development and application of a whole-blood-based assay to detect previous exposure to SARS-CoV-2. Whole blood is stimulated with SARS-CoV-2-derived peptides identified during assay development and stimulation-induced cytokines quantified using a multiplex testing platform. The resulting cytokine profiles are generated using computational tools to identify previous exposure to the virus. Results: The application of the assay revealed a lack of self-awareness of individuals' COVID-19 infection history and demonstrated the value of this new assay to assess the prevalence of SARS-CoV-2 exposure history and immunity in populations. Conclusions: Positive responses in this assay can facilitate the identification of underlying causes of unexplained symptoms and provide clinically actionable insights for healthcare applications, including in the continued conundrum of post-acute sequela of SARS-CoV-2 infection (PASC or "long COVID"), for which both diagnosis and management remain challenging.

RevDate: 2025-10-15
CmpDate: 2025-10-16

Arab Z, Shayanfar N, Mojaver MR, et al (2025)

Cardiopulmonary crosstalk in Long COVID: a systematic review of emerging evidence.

BMC cardiovascular disorders, 25(1):742.

BACKGROUND: Long COVID is a complex, multisystem syndrome with significant cardiopulmonary implications. Persistent inflammation, endothelial dysfunction, and microvascular injury contribute to prolonged symptoms such as dyspnea, chest pain, and exercise intolerance. Despite growing recognition of these complications, the underlying mechanisms of cardiopulmonary interactions remain poorly understood.

METHODS: A comprehensive literature search was conducted on PubMed, Scopus, Google Scholar, and Web of Science covering studies from 2019 to 2025. Keywords included "Long COVID", "cardiopulmonary interaction", "pulmonary fibrosis", "myocardial inflammation", and "endothelial dysfunction". A total of 102 articles were included, comprising 65 original research studies and 37 review articles.

RESULTS: Pulmonary sequelae, such as fibrotic remodeling, persistent hypoxia, and microthrombosis, impose significant strain on the cardiovascular system, exacerbating myocardial inflammation, arrhythmias, and endothelial dysfunction. Shared mechanisms, such as oxidative stress, immune dysregulation, and neurohumoral activation, create a vicious cycle of sustained cardiopulmonary impairment. The disruption of the renin-angiotensin-aldosterone system (RAAS) further contributes to systemic vascular dysregulation.

CONCLUSION: A deeper understanding of cardiopulmonary interactions in Long COVID is essential for developing effective management strategies. Targeting inflammatory pathways, restoring endothelial function, and addressing autonomic instability may provide therapeutic benefits. As the long-term impact of this syndrome continues to evolve, further research is needed to refine treatment approaches and mitigate its burden on global health.

RevDate: 2025-10-15

Silva AS, Dornelas R, JRLE Silva (2025)

Long COVID: persistent impacts and challenges for speech-language-hearing therapy.

CoDAS, 37(5):e20240291 pii:S2317-17822025000500200.

RevDate: 2025-10-15
CmpDate: 2025-10-15

Nagra G, Ezeugwu VE, Bostick GP, et al (2025)

Return-to-work for people living with long COVID: A scoping review of interventions and recommendations.

PloS one, 20(10):e0321891 pii:PONE-D-25-11140.

INTRODUCTION: Long COVID is characterized by the presence of new onset or persistent symptoms 3 months after a suspected or confirmed history of SARS-CoV-2 infection. It is a complex and multi-faceted condition that affects people in different ways. Long COVID affects individuals' labour market participation. While some cannot work, others may return to work (RTW) in a limited capacity. Determining what rehabilitation or related strategies are safe and effective for facilitating RTW is necessary.

OBJECTIVES: To synthesize evidence on RTW interventions for people living with Long COVID and to identify 'promising' interventions for enhancing work ability and RTW.

METHODS: We followed Arksey & O'Malley's methodology and the PRISMA extension for scoping reviews. Five electronic bibliographic databases and grey literature were searched. The literature search included various study designs, such as randomized controlled trials (RCT), quasi-experimental designs, and observational studies as well as clinical practice guidelines (CPGs). Two reviewers conducted screening and data extraction, with disagreements resolved through consensus. Intervention studies were categorized as promising (statistically significant RTW outcomes or ≥ 50% RTW), somewhat promising (20% to < 50% RTW), not promising (non-statistically significant RTW outcomes or < 20% RTW), or uncertain (did not specify proportion of RTW).

RESULTS: Twelve CPGs and nineteen intervention studies were identified. Of the intervention studies, 5 were cohort studies, 3 quasi-experimental studies, 4 observational, 2 interventional, 3 RCTs, and 2 case reports. Promising interventions included multimodal and interdisciplinary work-focused rehabilitation, multidisciplinary inpatient and outpatient rehabilitation, psychoeducation, pacing, and breathing strategies, shifting focus from symptom monitoring to optimizing functional outcomes, enhanced external counterpulsation inflatable pressure to improve blood flow, and constraint-induced cognitive therapy.

CONCLUSION: Many uncertainties remain regarding which RTW interventions are effective or the optimal characteristics of these interventions.

RevDate: 2025-10-15
CmpDate: 2025-10-15

Begum S, Mirghani HO, Alhowiti A, et al (2025)

Prevalence and risk factors for post-COVID-19 syndrome on medical students in Tabuk, Saudi Arabia-2023-2024.

Journal of family medicine and primary care, 14(9):3729-3734.

BACKGROUND: COVID-19 has infected 221 million individuals worldwide and new strains are discovered continuously. An important complication is the post-COVID-19 syndrome that affects various organs with substantial morbidities. Studies on post-COVID-19 symptoms and risk factors are scarce. We aimed to assess the same among medical students at the University of Tabuk, Saudi Arabia.

METHODOLOGY: This cross-sectional study was conducted among 424 medical students at the University of Tabuk, Saudi Arabia, during the period from July 2023 to October 2024. A web-based questionnaire detailing the demographic factors, post-COVID-19 symptoms, comorbidities, vitamin D deficiency, and the cumulative grade average (GPA) was used.

RESULTS: Out of the 424 students, 38.2% were overweight and 9.4% were obese, 26.9% had bronchial asthma, and diabetes was found in 11.8%. Smoking was observed in 25%, and 58.5% were vitamin D deficient, while 22.6% were hospitalized with COVID-19. The majority of students received > two doses (74.1%), 24.5% received two doses, and 1.4% received one dose. The majority (80.7%) of students reported at least one post-COVID-19 symptom, and headache was the commonest symptom (63.7%), followed by cough in 50.5%. The absence from classrooms was 54.2%, 32.1%, and 13.7% (3 days, 3-8 days, and >10 days/month, respectively), and 44.8% thought that long COVID-19 negatively affected their GPA.

CONCLUSION: Post-COVID-19 syndrome was associated with diabetes, bronchial asthma, and vitamin D deficiency, odd ratios, 95% CI, 0.011-0.910, 0.005-0.312, 0.203-0.821, respectively, P values > 0.05. No significant association was found regarding, age, gender, and smoking, P values >0.05.

RevDate: 2025-10-15
CmpDate: 2025-10-15

Albazee E, Alajmi SA, Alkandari AM, et al (2025)

Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Cureus, 17(10):e94386.

A notable rise in olfactory dysfunction (OD) prevalence has been observed since the COVID-19 pandemic. COVID-19-related OD is associated with several consequences, especially deteriorated quality of life. Hence, several treatment options have been investigated, with platelet-rich plasma (PRP) showing promising results. A systematic review and meta-analysis summarizing randomized controlled trial (RCT) evidence were retrieved from PubMed, Google Scholar, Scopus, and Web of Science up to June 2025. The risk of bias was assessed using the Cochrane Risk of Bias 2 assessment tool. Data were analyzed using Stata MP version 18 (StataCorp LLC, College Station, TX), pooling dichotomous outcomes as relative risks (RRs) and continuous outcomes as standardized mean differences (SMDs), each with 95% confidence intervals (CIs). Four RCTs, including 198 participants, were included in our meta-analysis. PRP significantly improved objective olfactory scores (SMD = 1.86, 95% CI (0.14, 3.57), p = 0.03) and subjective olfactory scores (SMD = 0.92, 95% CI (0.32, 1.51), p < 0.001). Additionally, PRP significantly increased the response rate (RR = 1.79, 95% CI (1.14, 2.81), p = 0.01). PRP was generally well-tolerated across the included trials, with no major adverse events reported. Two RCTs showed an overall low risk of bias, one trial showed some concerns, and another showed a high risk of bias. With uncertain evidence, PRP may improve both objective and subjective smell function and clinical outcomes in people with long COVID-related OD. PRP treatment was reported to be safe, with minor, temporary side effects primarily related to the procedure. Although initial results are promising, the small number of RCTs requires a cautious approach to interpretation.

RevDate: 2025-10-15
CmpDate: 2025-10-15

Blitshteyn S, Funez-dePagnier G, Szombathy A, et al (2025)

Immunotherapies for postural orthostatic tachycardia syndrome, other common autonomic disorders, and Long COVID: current state and future direction.

Frontiers in cellular and infection microbiology, 15:1647203.

Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope, and orthostatic hypotension are the most common autonomic disorders encountered in clinical practice. The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. However, the treatment of common autonomic disorders has traditionally included pharmacologic and non-pharmacologic symptomatic therapies as the standard approach. Unfortunately, these symptomatic therapies have been of limited or insufficient efficacy to meaningfully improve functional status or result in recovery, especially in patients with severe symptoms. Case reports, case series, and clinical experience suggest that intravenous and subcutaneous immunoglobulin, as well as other immunologic therapies (such as plasmapheresis, corticosteroids, and rituximab), may be effective in some patients with severe POTS and other common autonomic disorders who are refractory to standard therapies. In this narrative review, we summarize the literature available on the topic of immunotherapies for POTS, other common autonomic disorders, and Long COVID. We also highlight the need for large, multicenter, placebo-controlled trials of immunoglobulin, plasmapheresis, intermittent corticosteroids, and other repurposed immunotherapies in patients with common autonomic disorders who have significant functional impairment.

RevDate: 2025-10-15
CmpDate: 2025-10-15

Portela MC, Escosteguy CC, Lima SML, et al (2025)

Healthcare gaps and inequities following hospitalisation for COVID-19 in Brazil's universal healthcare system: a patient-engaged survey of Long COVID healthcare needs, use and barriers.

International journal for equity in health, 24(1):275.

BACKGROUND: Long COVID (LC) is an infection-associated chronic condition (IACC) that tends to be neglected by healthcare systems. Studies of post-COVID healthcare utilisation find elevated levels of use but have mainly been conducted in high-income settings. In the context of Brazil's universal health system (SUS), our patient-engaged study aimed to map healthcare needs, use, and access barriers related to LC up to 24 months following COVID-19 hospitalisation, in the interest of informing health system planning for an equitable LC response.

METHODS: A cohort survey included a probabilistic sample of hospitalised COVID-19-confirmed individuals aged ≥ 18, who had been discharged from public hospitals in Rio de Janeiro between December 2020 and November 2022. Socio-demographic and clinical data were collected, including self-reported LC symptoms, self-reported LC, healthcare needs, use, and access barriers.

RESULTS: In a sample of 556 participants, corresponding to an estimated population of 11,328 individuals, 50.0% (95%CI 44.3-55.6%) reported healthcare needs in the six months prior, due to new-onset or worsened conditions after COVID-19. Almost 45.0% did not complete high school, while 26.5% lived below the poverty line (~ US$6.85 per day), indicating a high proportion of socially vulnerable individuals. High prevalence of LC symptoms, self-reported LC, and new diagnoses were observed. Healthcare needs were associated with acute disease severity, number of LC symptoms, and new post-COVID diagnoses, including cardiovascular and kidney diseases, and endocrine and musculoskeletal disorders. Significant gaps existed between need and access to services, and part of the access to services involved substantial out-of-pocket expenditure. These gaps were particularly pronounced for specialised medical services, scans/imaging, post-COVID rehabilitation services, and mental healthcare. Despite a universal health system, those with higher monthly incomes (above R$1,500 or ~ US$250) were more likely to have accessed specialised medical care.

CONCLUSIONS: The SUS is not meeting the high need for LC healthcare, raising concerns about deepening health inequities. In Brazil, as elsewhere, LC joins other IACCs in becoming an invisibilised epidemic, with LC patients, especially those unable to pay for care, neglected amid general healthcare backlogs. A comprehensive pandemic response must include dedicated efforts to surveil and treat the long-term impacts of infection.

RevDate: 2025-10-14

Yonker LM, Dredge D, Munro A, et al (2025)

The second-order effects that the COVID-19 pandemic has had on pediatric populations.

Expert review of anti-infective therapy [Epub ahead of print].

INTRODUCTION: There is growing recognition that SARS-CoV-2 can have long-term health consequences that persist beyond acute infection. While the long-term health impact of SARS-CoV-2 is evident in adults and the elderly, the impact on children and adolescents remains under recognized. In this paper, we navigate the second-order post-acute effects that the COVID-19 has had on the pediatric populations, with the exception of mental health implication of social restrictions, out of the scope of this review.

AREAS COVERED: We outline common scenarios related with SARS-CoV-2 infection encountered in pediatric clinical practice, such as in the Multisystem inflammatory syndrome (MIS-C), Long Covid, neurological and autoimmune complications of Covid-19, immunological impact of the viral infection, as well as epidemiological and public health consequences associated with the implementation of non-pharmacological interventions.

EXPERT OPINION: SARS-CoV-2 has had several second-order effects on child health, from a biological, epidemiological, and public health perspective, highlighting the complexity of dealing with new infections and the urgent need to implement multidisciplinary interventions that support the health of people at single person and societal level. Funding on modern surveillance system, preventing strategies and research to better understand and cure post-acute complications of viral infections should be a priority of every funding agency.

RevDate: 2025-10-14

Tanaka H, Kubota E, Otori N, et al (2025)

Olfactory cleft adhesion in post-COVID-19 olfactory dysfunction.

European annals of otorhinolaryngology, head and neck diseases pii:S1879-7296(25)00135-8 [Epub ahead of print].

Post-COVID-19 olfactory dysfunction (PCOD) typically resolves within weeks to months; however, persistent cases exist in approximately 10% of patients beyond a year. This study investigated the role of olfactory cleft adhesions in prolonged PCOD and evaluated surgical intervention as a treatment option. Four cases of PCOD unresponsive to medical therapy underwent endoscopic sinus surgery (ESS) to address bilateral olfactory cleft obstruction identified on computed tomography (CT) scan. Adhesions between the superior/middle turbinates and nasal septum were surgically divided, and silicone plates were inserted to prevent reattachment. All patients reported significant subjective improvements in olfaction within one week of silicone removal. Objective olfactory test scores continued to improve over subsequent months, and postoperative CT scan confirmed improved ventilation of the olfactory cleft. These findings suggest that adhesions formed during inflammatory healing contribute to conductive olfactory dysfunction in Long-COVID cases, distinct from sensorineural or central OD. Surgical intervention may be beneficial for carefully selected patients with PCOD persisting for at least one year, anosmia or severe olfactory loss confirmed by testing, and CT evidence of olfactory cleft obstruction. However, the risks such as mucosal damage and potential worsening or no improvement of OD should be discussed thoroughly. Individualized treatment strategies are recommended, and further studies are warranted to optimize management of persistent PCOD.

RevDate: 2025-10-14

Grafström T, Barros GWF, Persson IL, et al (2025)

Post COVID-19 condition phenotypes: A prospective cohort study identifying four symptom clusters and their impact on long-term outcomes.

Journal of infection and public health, 18(12):102994 pii:S1876-0341(25)00343-0 [Epub ahead of print].

BACKGROUND: Current evidence indicates that Post COVID-19 Condition (PCC) is multifaceted with distinct phenotypes. While previous studies have identified symptom clusters-commonly featuring fatigue, respiratory symptoms, and cognitive impairment-findings have been inconsistent, and no clear consensus exists. Moreover, how these symptom clusters evolve over time, particularly beyond the first year post-infection, remains poorly understood.

METHODS: This multicentre prospective cohort study included 470 hospitalised and non-hospitalised adult individuals from the CoVUm study across four sites in Sweden between 2020 and 2021. Follow-ups were conducted up to 3 years after infection to assess persistent symptoms, health-related quality of life (HRQoL), and work capacity. Symptom clusters at 6 months were identified via hierarchical cluster analysis, and participants were tracked using a k-nearest neighbour algorithm.

RESULTS: The most common symptoms at 6 months were fatigue (33 %), dyspnoea (32 %), mental fatigue (30 %), and concentration difficulties (28 %), with a median EQ-5D-5L index of 0.98 (IQR 0.93-1). Four distinct symptom clusters were identified: (i) "Few Symptoms" (n = 265, 57 %), (ii) "Respiratory Symptoms" (n = 66, 14 %), (iii) "Neurocognitive Symptoms" (n = 75, 16 %), and (iv) "Multisystem Symptoms" (n = 52, 11 %). Participants in the latter three clusters were older, had more comorbidities, and were more often hospitalised during primary COVID-19 infection. These clusters also had significantly lower HRQoL compared to the "Few Symptoms" cluster. Over time, more than half of participants transitioned to a cluster with fewer or no symptoms, with significant perceived HRQoL improvement in the "Multisystem Symptoms" cluster.

CONCLUSION: While many patients with PCC improved over time, a subset had persistent symptoms at 3 years, especially if primary infection required hospitalisation. The identification of symptom clusters and their trajectories over time contributes to a better understanding of PCC heterogeneity, ultimately bringing the field closer to consensus on the classification and long-term impact of PCC.

RevDate: 2025-10-14

Kippenbroek N, Stölting A, Schröder D, et al (2025)

[Inflammatory rheumatic diseases in patients with post-COVID syndrome].

Zeitschrift fur Rheumatologie [Epub ahead of print].

BACKGROUND: The post-COVID syndrome (PCS) describes long-lasting symptoms after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PCS and rheumatic diseases, especially collagenoses, show strong overlap of symptoms and biomarkers. Thus far, no biomarkers that differentiate between PCS patients with and without rheumatic diseases exist, and data on the prevalence of rheumatic diseases in this collective in Germany is scarce.

METHOD: Based on the online platform DEFEAT-Corona, 80 people with PCS without a previously confirmed inflammatory rheumatic disease (IRD) and interest in a rheumatological evaluation were recruited. Typical complaints of PCS and rheumatic diseases were analyzed. In addition, comprehensive laboratory analyses were conducted.

RESULTS: In 6.25% (n = 5) of the PCS patients,IRD was suspected or confirmed. The remaining 75 PCS patients without IRD also showed a high degree of overlap with regard to complaints typical for rheumatic disease or PCS. The inflammation parameters C‑reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly higher in PCS patients with suspected IRD compared to patients with PCS only and significantly more often exceeded normal range.

CONCLUSION: This study illustrates the high degree of overlap between PCS and rheumatic symptoms in PCS patients without previous suspicion of IRD. The risk for IRD could be elevated in PCS. However, in the view of the authors, PCS without additional risk factors, such as elevated CRP or arthritis, does not generally justify rheumatological evaluation in clinical routine. This recommendation should be further investigated in larger studies.

RevDate: 2025-10-14

Stufano A, G Lucchese (2025)

Work Productivity Loss in People Living With Long COVID Symptoms: a good start and a missed opportunity.

Journal of occupational and environmental medicine pii:00043764-990000000-01006 [Epub ahead of print].

RevDate: 2025-10-14

Naik H, W Zhang (2025)

Re: Work Productivity Loss in People Living With Long COVID Symptoms: a good start and a missed opportunity.

Journal of occupational and environmental medicine pii:00043764-990000000-01005 [Epub ahead of print].

RevDate: 2025-10-14

Hadidchi R, Ali E, Piskun H, et al (2025)

Elevated Risk of Long-Term Decline in Left Ventricular Ejection Fraction After COVID-19.

Journal of the American Heart Association [Epub ahead of print].

BACKGROUND: COVID-19 has been linked to cardiovascular complications, but its long-term impact on left ventricular (LV) function is unclear. We investigated whether SARS-CoV-2 infection is associated with increased risk of LV ejection fraction (LVEF) decline and whether vaccination mitigates this risk.

METHODS: In this retrospective study, we included patients with COVID-19, normal baseline LVEF (≥50%), and at least one follow-up echocardiogram from 2016 to 2024. Outcomes were LVEF dropping <50%, 40%, and 30%. Multivariable Cox models adjusted for demographics, comorbidities, vaccination status, and baseline LVEF. Associations with acute-phase blood biomarkers were examined.

RESULTS: Among 2853 patients who were COVID+ and 3963 patients who were COVID- (baseline LVEF ≥50%), patients with COVID-19 had lower mean follow-up LVEF (60.65% versus 61.53%, P<0.005) and higher rates of LVEF decline <50%, 40%, and 30%. Both hospitalized (adjusted hazard ratio [aHR], 1.57 [1.30-1.91]) and non-hospitalized (aHR, 1.48 [1.18-1.85]) patients with COVID-19 had greater risk of LVEF <50% versus controls; only hospitalized patients had significantly increased risk of LVEF<40% (aHR, 1.81 [1.35-2.43]) and <30% (aHR, 2.79 [1.72-4.54]). Vaccination was not significantly associated with LVEF decline. Baseline LVEF, older age, male sex, history of heart failure, myocardial infarction, and chronic kidney disease were associated with greater risk. Elevated troponin, B-type natriuretic peptide, D-dimer, and thrombocytopenia predicted greater risk in hospitalized patients with COVID-19.

CONCLUSIONS: SARS-CoV-2 infection is associated with long-term LVEF declines, especially in hospitalized patients. Vigilant cardiac surveillance may be needed in survivors of COVID-19 to mitigate progressive dysfunction.

RevDate: 2025-10-14

Troxel AB, Krishnan JA, M Verduzco-Gutierrez (2025)

The 2024 NASEM Long COVID Definition as a Starting Point for Research.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Although new treatments and vaccines have greatly reduced the acute threat of covid-19, many people who contract the disease find themselves with a persistent set of symptoms that are at best uncomfortable and at worst debilitating — long covid. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

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Curriculum Vitae for R J Robbins

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