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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 17 Sep 2025 at 01:51 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: 2025-09-16
CmpDate: 2025-09-16

Maybin JA, Walker C, Watters M, et al (2025)

The potential bidirectional relationship between long COVID and menstruation.

Nature communications, 16(1):8187.

Women have reported menstrual changes following SARS-CoV-2 infection and variation in long COVID symptoms across the menstrual cycle. We examined (i) whether COVID is linked to abnormal uterine bleeding (AUB), (ii) if long COVID symptoms vary with the menstrual cycle, and (iii) potential underlying mechanisms. Here we show long COVID was associated with AUB in a UK population. When compared to those never infected (n = 9423), long COVID participants (n = 1048) reported increased menstrual volume, duration and intermenstrual bleeding, while those who recovered from acute COVID (n = 1,716) reported minimal menstrual disruption. Long COVID symptoms examined in 54 women across the menstrual cycle revealed that severity was highest during the perimenstrual and proliferative phases. Serum and endometrial analysis revealed higher serum 5α-dihydrotestosterone and lower endometrial androgen receptors in long COVID versus no COVID. Other ovarian hormones showed no significant differences. Serum cytokine profiling indicated increased menstrual inflammation with long COVID and immune cell aggregates were observed in menstrual endometrium. In conclusion, long COVID was associated with AUB but not impaired ovarian function. Differences in peripheral and endometrial inflammation may contribute to AUB and long COVID symptom severity. We anticipate our findings will instigate exploration of new therapeutic strategies for women with long COVID.

RevDate: 2025-09-16

Naushad Z, Malik J, Mishra AK, et al (2025)

Artificial Intelligence in Cardiovascular Health: Insights into Post-COVID Public Health Challenges.

High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension [Epub ahead of print].

Cardiovascular diseases (CVDs) continue to be the topmost cause of the worldwide morbidity and mortality. Risk factors such as diabetes, hypertension, obesity and smoking are significantly worsening the situation. The COVID-19 pandemic has powerfully highlighted the undeniable connection between viral infections and cardiovascular health. Current literature highlights that SARS-CoV-2 contributes to myocardial injury, endothelial dysfunction, thrombosis, and systemic inflammation, increasing the severity of CVD outcomes. Long COVID has also been associated with persistent cardiovascular complications, including myocarditis, arrhythmias, thromboembolic events, and accelerated atherosclerosis. Addressing these challenges requires continued research and public health strategies to mitigate long-term risks. Artificial intelligence (AI) is changing cardiovascular medicine and community health through progressive machine learning (ML) and deep learning (DL) applications. AI enhances risk prediction, facilitates biomarker discovery, and improves imaging techniques such as echocardiography, CT, and MRI for detecting coronary artery disease and myocardial injury on time. Remote monitoring and wearable devices powered by AI enable real-time cardiovascular assessment and personalized treatment. In public health, AI optimizes disease surveillance, epidemiological modeling, and healthcare resource allocation. AI-driven clinical decision support systems improve diagnostic accuracy and health equity by enabling targeted interventions. The integration of AI into cardiovascular medicine and public health offers data-driven, efficient, and patient-centered solutions to mitigate post-COVID cardiovascular complications.

RevDate: 2025-09-16
CmpDate: 2025-09-16

Corrêa-Dias LC, Lopes-Ribeiro Á, Mendes GER, et al (2025)

A pain from the nose to the head: neurological commitment during long COVID.

Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74(1):127.

BACKGROUND: Long COVID is a debilitating illness with multi-systemic symptoms that affects at least 10% of individuals who have had COVID-19. Symptoms include respiratory, dermatological, gastrointestinal, cardiovascular, and most frequently reported, neurological sequelae. The most common neurological manifestations include fatigue, brain fog, memory issues, attention disorder, and headaches.

METHODS: In this review, we explore the current literature and highlight key findings regarding not only the clinical presentations of neurological commitment during long COVID but mainly the mechanisms that culminate in neuroinflammation, such as autoimmunity, viral reservoirs, and lack of surveillance of T-cells.

RESULTS: Neuroinflammation is a complex multicellular response that directly impacts microglial cells and includes inflammasome activation, trafficking of immune cells, and increased circulating autoantibodies, cytokines, and chemokines in the central nervous system, directly impacting the tissue homeostasis. This review provides important information beyond the clinical manifestations of long COVID. Here, we highlight multifactorial neuroinflammation as the main mechanism involved in long COVID, bringing together several studies that address the different mechanisms that culminate in inflammation of the central nervous system, and highlight possible biomarkers involved in this syndrome and potential therapeutic approaches that have been studied.

CONCLUSION: Thus, this review strengthens research into long COVID and provides new possibilities for future studies.

RevDate: 2025-09-16

Cunha BLM, Policarpo JH, Silva JRD, et al (2025)

Whole body vibration exercise effects on exercise capacity and muscle strength in long Covid-19 patients: A randomized clinical trial.

Journal of bodywork and movement therapies, 44:494-500.

RevDate: 2025-09-16
CmpDate: 2025-09-16

Vu PD, Bansal V, Lin MJ, et al (2023)

Sphenopalatine Ganglion Block for Postacute Sequelae SARS-CoV-2 Infection Headaches: A Case Report and Review of the Literature.

Pain medicine case reports, 7(3):157-161.

BACKGROUND: In a subset of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), neurological symptoms including "brain fog" and headache persist beyond the acute phase of the infection, often referred to as postacute sequelae SARS-CoV-2 infection (PASC), or Long COVID. Current practice supports a multi-modal approach to address PASC symptoms. One technique for chronic headaches not utilized for PASC is sphenopalatine ganglion blocks (SPGB). We evaluate the pathophysiology of PASC headaches, review the utilization of sphenopalatine ganglion blocks in primary headaches, and discuss the potential for SPGB in PASC headaches.

CASE REPORT: We present a patient with PASC headaches who failed various conservative and interventional therapies. Worsening symptoms resulted in pursuing bilateral SPGB, resulting in an 80% improvement in symptoms. To our knowledge, we report the first PASC headache treated with an SPGB via infrazygomatic injection.

CONCLUSION: SPGB can treat PASC headaches and improve a patient's quality of life.

RevDate: 2025-09-16
CmpDate: 2025-09-16

Uhlenhopp R, Taylor C, Tomlinson H, et al (2023)

Alleviation of COVID-19 Parosmia with Stellate Ganglion Block: A Case Report.

Pain medicine case reports, 7(3):101-104.

BACKGROUND: An estimated 23 million people in the United States are affected with Long COVID, formally called Postacute Sequelae SARS-CoV-2 infection (PASC). Disturbances of taste and smell are common symptoms. There is limited evidence for effective treatment.

CASE REPORT: A 68-year-old woman contracted COVID-19 in January 2021. She had worsening parosmia and dysgeusia, described as "rancid" smells with a variety of foods and objects. She underwent successful right stellate ganglion block in April 2022. Immediately after the procedure, she was able to comfortably eat food previously intolerable. Benefits persisted at 5- and 30-day follow-up.

CONCLUSIONS: An ever-expanding patient population and lack of treatment options emphasize the importance of continued research into the pathogenesis and treatment of PASC. A nascent body of evidence suggests stellate ganglion block may provide durable relief.

RevDate: 2025-09-15
CmpDate: 2025-09-15

van der Bie J, Coleon A, Visser D, et al (2025)

Post Pandemic Problem, is there an animal model suitable to investigate PASC.

Npj imaging, 3(1):41.

Although the COVID-19 pandemic is no longer a global health emergency, many patients still suffer from long-term effects, known as post-acute sequelae of COVID-19 (PASC) or long COVID. Understanding its complex pathophysiology requires animal models replicating the post-acute phase, which may aid in developing, the urgently needed, therapeutics. Our review assessed and summarized 81 studies from 1979 manuscripts. In addition, a second table summarizing the imaging findings of 26 studies related to this topic was added, based on a separate literature search of 797 manuscripts. In humans a SARS-CoV-2 infection, the sequelae and possible development of PASC is heterogenic. The same holds true for experimental animal models. While several models are suitable to address different research questions, no single model can fully replicate all aspects of PASC. Imaging plays a crucial role in visualizing these aspects, especially since questionnaires, the primary diagnostic tool in humans, cannot be used in animals. Thus, imaging allows the investigation of pathophysiology in a controlled setting, offering valuable insights. This review summarizes the available animal models and imaging modalities used in PASC research. Our aim is to provide researchers with guidance on selecting the most appropriate model and imaging technique to address their specific research questions.

RevDate: 2025-09-15

Holtjer JCS, Houweling L, Bloemsma LD, et al (2025)

Defining a long COVID 'expotype' within the P4O2 COVID-19 study.

Environmental research pii:S0013-9351(25)02112-7 [Epub ahead of print].

INTRODUCTION: Long COVID is estimated to affect at least 10% of COVID-19 patients, with fatigue being a common complaint. The combined contribution of environmental factors (i.e. exposome) has been associated with COVID-19 severity, however its association with long COVID remains underexplored. This study aims to identify possible exposome phenotypes ('expotypes') related to long COVID severity.

METHODS: We recruited 95 long COVID patients in the Netherlands and assessed a range of factors and symptoms at 3-6 months post-infection. Fatigue (FSS), Quality of Life (QoL) and fatigue over time were used as indicators of long COVID severity. We included air pollutants (n=4), and neighborhood characteristics (n=7). We performed frequentist and Bayesian analyses to determine factors associated with long COVID severity. Models were adjusted for age, BMI, education level, and sex.

RESULTS: We found population density (odds ratio (OR)[95%Confidence interval(CI)]=1.03[1.01-1.06]) and light at night (OR[95%CI]=0.95[0.90-1.00]) to be associated with fatigue. Decreased odds for having an optimal QoL score was found for increased distance to blue space (OR[95%CI]=0.41[0.15-0.93]) in the single exposure model. No significant associations were found for any exposure variables and fatigue over time. No exposure variables were selected in penalized regression models for any outcome.

DISCUSSION: The external exposome could be associated with fatigue severity and QoL in long COVID patients, however these associations were not found in the horseshoe model. Prevention strategies and urban planning could take these associations into account to optimize the living environment, however more research is needed to validate and investigate the impact of these results.

RevDate: 2025-09-15

Preiss A, Bhatia A, Aragon LV, et al (2025)

Effect of Paxlovid treatment during acute COVID-19 on Long COVID onset: An EHR-based target trial emulation from the N3C and RECOVER consortia.

PLoS medicine, 22(9):e1004711 pii:PMEDICINE-D-24-02349 [Epub ahead of print].

BACKGROUND: Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. This study tests whether Paxlovid treatment in the acute phase of COVID-19 could help prevent the onset of PASC.

METHODS AND FINDINGS: We used electronic health records from the National Clinical Cohort Collaborative to define a cohort of 445,738 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation framework to estimate the effect of Paxlovid treatment on PASC incidence. We emulated a series of six sequential trials: one for each day of a 5-day treatment grace period. For each sequential trial, the treatment group was defined as patients prescribed Paxlovid on the trial start day, and the control group was defined as all patients meeting eligibility criteria who remained untreated on the trial start day. We pooled individual record-level data from the sequential trials for analysis. The follow-up period was 180 days. The primary outcome was overall PASC incidence measured using a computable phenotype. Secondary outcomes were incident cognitive, fatigue, and respiratory symptoms in the post-acute period. We controlled for a wide range of demographic and medical history covariates. Compared to the control group, Paxlovid treatment did not have a significant effect on overall PASC incidence or incident respiratory symptoms. It had a small protective effect against cognitive (relative risk [RR] 0.91; 95% CI [0.84, 0.98]; p = 0.019) and fatigue (RR 0.94; 95% CI [0.90, 0.98]; p = 0.002) symptoms. Finally, we estimated Paxlovid's effect on overall PASC incidence across strata of age, COVID-19 vaccination status, and Charlson Comorbidity Index (CCI) prior to COVID-19. We found small protective effects among patients aged 65 years or more (RR 0.92; 95% CI [0.88, 0.97]; p < 0.001; absolute risk difference [ARD] -0.43%; number needed to treat [NNT] 233) and with a CCI of 3 or 4 (RR 0.83; 95% CI [0.75, 0.92]; p < 0.001; ARD -1.30%; NNT 76). This study's main limitation is that the causal interpretation relies on the assumption that we controlled for all confounding variables.

CONCLUSIONS: Although some prior observational studies suggested that Paxlovid held promise as a PASC preventive, this study-with a large, nationally sampled cohort; a contemporary study period; and causal inference methodology-found that Paxlovid treatment during acute COVID-19 had no effect on subsequent PASC incidence. Stratified analyses suggest that Paxlovid may have a small protective effect among higher-risk patients, but the NNT is high. In conclusion, we see Paxlovid as unlikely to become a definitive solution for PASC prevention.

RevDate: 2025-09-15
CmpDate: 2025-09-15

Parthasarathy S, Brosnahan S, Sieberts S, et al (2025)

Wearable-derived Sleep Measurements are Associated with Long-COVID in the RECOVER Adult Cohort.

Research square pii:rs.3.rs-7422764.

Wearables yield a wide array of sleep-related measures that are relevant to Long COVID. We leveraged wearables-derived sleep measures (WDSM) to identify differences between individuals with Long COVID (LC) versus individuals with possible or no LC in the RECOVER adult cohort. We found significant associations between LC and reduced heart rate variability measured during sleep and increased nightly variability in sleep duration after adjusting for confounders. Moreover, LC was independently associated with lower sleep efficiency, greater variability of nighttime sleep timing, higher resting heart rate, lower respiratory rate during rapid eye movement (REM) sleep, prolonged REM sleep onset latency, worse global physical and mental health. Cluster analysis identified distinct multidimensional patterns of WDSM that are associated with LC and quality of life. Together, the strong association between WDSM, or WDSM clusters, with LC provides a potential biomarker for future validation efforts to detect LC and monitor treatment effectiveness.

RevDate: 2025-09-15
CmpDate: 2025-09-15

Matviichuk A, Krasnienkov D, Yerokhovych V, et al (2025)

Association of leukocyte telomere length and HbA1c with post-COVID-19 syndrome in type 2 diabetes: a cross-sectional pilot study.

Frontiers in medicine, 12:1628156.

INTRODUCTION: Leukocyte telomere length is considered a promising prognostic marker associated with COVID-19 severity, adverse outcomes (hospital admission, need for critical care, and respiratory support), and mortality. However, the contribution of telomere length to post-COVID-19 syndrome (PCS) development is unclear.

AIM: This study aimed to evaluate the association between telomere shortening and the course of PCS in patients with type 2 diabetes (T2D) and to determine whether telomere length is linked to clinical phenotype, gender, and biological age.

MATERIALS AND METHODS: In this cross-sectional study, 66 T2D patients who had recovered from COVID-19 were enrolled. Patients were divided into two groups depending on PCS development: the PCS group (n = 44) and patients who did not develop PCS (n = 22) within 6 months after COVID-19 infection. Relative telomere length was determined using the standardized method proposed by Cawthon et al. A range of machine learning models was developed for PCS prediction. These models underwent training utilizing a cross-validation approach, as well as internal validation.

RESULTS: We observed a significantly lower mean of telomere length in T2D patients with PCS as compared to those without it (1.09 ± 0.19 and 1.28 ± 0.24; p = 0.001). In the sub-analysis, shorter telomeres were observed in female patients and patients of older age in both groups. The mean telomere length did not differ significantly among clinical phenotypes of PCS (p = 0.193). The best model generated for PCS prediction was the gradient boosting machine (GBM), which achieved an AUC of 0.753. The most influential variables across the top 10 models included telomere length, HbA1c, vitamin D3, waist circumference, ApoA1, C peptide, ApoB, COVID-19 severity, duration of T2D, IL-6, cholesterol, BMI, and age. Leukocyte telomere length and HbA1c exhibited significantly greater impact than other features.

CONCLUSION: Shorter telomere length and higher HbA1c levels were significantly associated with the presence of PCS in our cohort of individuals with T2D. These factors may represent potential biomarkers that warrant further investigation.

RevDate: 2025-09-15
CmpDate: 2025-09-15

Meiler S, Schmalenberger D, Malfertheiner M, et al (2025)

Chest computed tomography findings do not influence the decision of pneumologists regarding the diagnosis and management of pulmonary long coronavirus disease: a single center retrospective study.

Journal of thoracic disease, 17(8):5654-5662.

BACKGROUND: Pulmonary symptoms are common in long coronavirus disease (COVID), yet the diagnostic value of chest computed tomography (CT) in these patients remains unclear, particularly when physical examination and pulmonary function tests are normal. This study investigates whether chest CT influences the decision of pneumologists regarding the measures taken for diagnostic work-up, the final diagnosis, the confidence in the diagnosis, and the downstream management of patients suspected to suffer from pulmonary long COVID.

METHODS: All patients presented in a dedicated long COVID outpatient clinic of a secondary care hospital that specializes in lung diseases between April 2020 and August 2021. Inclusion criteria were age ≥18 years, suspicion for long COVID syndrome of pulmonary origin according to the National Institute for Health and Care Excellence (NICE) criteria and availability of a chest CT acquired during work-up. Three pneumologists evaluated the patient's records in two rounds (round 1 without and round 2 with knowledge of CT results). Identical parameters were queried in the two runs: diagnosis of pulmonary long COVID, confidence of the diagnosis on a scale from 0 to 3, need for: bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), cryobiopsy, video-assisted thoracoscopy (VATS), ergospirometry, ventilation/perfusion scintigraphy, follow-up appointment, rehabilitation.

RESULTS: Forty-one patients were included (24 male; age 21 to 72 years, mean 55 years). In the first and second round diagnosis of pulmonary long COVID was made in an average of 10 (24%) and 11 (27%) patients (P=0.69). Confidence of diagnosis was 1.9 and 2.6 (P<0.001). No statistical difference was found regarding the frequency of diagnostic measures and downstream management.

CONCLUSIONS: Chest CT did not influence the diagnostic decision of pneumologists for patients suspected to suffer from pulmonary long COVID. However, the confidence in the diagnosis was improved by chest CT. Still, based on our results chest CT does not routinely have to be included in the work-up of long COVID, when pulmonary function tests and auscultation are normal.

RevDate: 2025-09-15
CmpDate: 2025-09-15

Li X, Chen Y, Sun S, et al (2025)

Association between electrolyte supplementation and cardiac injury in long COVID-19.

Journal of thoracic disease, 17(8):5993-6003.

BACKGROUND: Cardiac injury is a common complication of long coronavirus disease 2019 (COVID-19), affecting heart function and quality of life. This study aimed to investigate the association between electrolyte supplementation and cardiac injury in long COVID-19.

METHODS: This retrospective study was conducted at Guangdong Provincial People's Hospital Zhuhai Hospital (Zhuhai Golden Bay Hospital), utilizing data from patients with cardiac injury related to long COVID-19 who were admitted and managed between January 2021 and January 2023. The patients were grouped according to electrolyte supplementation (supplementation group) or no supplementation (control group). The outcomes included heart rate variability (HRV) parameters, the Minnesota Heart Failure Quality of Life questionnaire, and numerical rating scale (NRS) assessments of quality of life.

RESULTS: A total of 144 patients with cardiac injury related to long COVID-19 were included in the analysis (supplementation group, n=72; control group, n=72). After adjusting for age, sex, creatinine, total cholesterol, and low-density lipoprotein, multivariable linear regression analysis indicated a significant association between supplementation and increased levels of potassium [β=1.3, 95% confidence interval (CI): 1.1-1.5, P=0.001] and magnesium (β=0.18, 95% CI: 0.07-0.29, P=0.001), as well as improvements in HRV parameters, including standard deviation of normal-to-normal RR intervals over 24 hours, root mean square of successive differences, and high-frequency domain indices/low-frequency domain indices (all P<0.05). Additionally, supplementation correlated with a reduced frequency of premature contractions (β=-5.61, 95% CI: -7.50 to -3.72, P=0.01), lower Minnesota scores (β=-6.7, 95% CI: -9.1 to -4.3, P=0.001), and decreased NRS scores (β=-7.2, 95% CI: -6.5 to -7.9, P=0.02).

CONCLUSIONS: Electrolyte supplementation may be beneficial in managing cardiac injury associated with long COVID-19. Further research is needed to clarify the role of electrolytes in cardiac injury related to long COVID-19 and to explore management strategies that incorporate electrolyte supplementation.

RevDate: 2025-09-15
CmpDate: 2025-09-15

Tusconi M, Dursun SM, Pegreffi F, et al (2025)

Bipolar spectrum, hypothyroidism, and their association with chronic fatigue/myalgic encephalomyelitis-like syndrome in long COVID: could they be identified as early determinants?.

Frontiers in psychiatry, 16:1623288.

BACKGROUND: Long COVID has been increasingly linked to persistent clinical manifestations, including chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). However, the relationship between this syndrome and pre-existing conditions such as bipolar spectrum disorders and hypothyroidism is not yet clearly established. These disorders may influence the regulation of biorhythms and immune function, suggesting a possible role in the predisposition to the development of CFS/ME in the context of long-term COVID-19.

OBJECTIVES: This study investigates the prevalence of hypothyroidism and bipolar spectrum disorders in patients with CFS/ME associated with long-term COVID-19. It compares it with pre-pandemic population data to determine whether these conditions may be predisposing factors.

METHODS: A case-control design was used to select cases from a clinical trial on CFS/ME in long COVID, while controls were extracted from pre-COVID epidemiological databases. Comparative statistical analyses, including chi-square tests and analysis of variance (ANOVA), were performed to assess significant differences in the frequency of these conditions between both groups.

RESULTS: The clinical sample showed significantly higher prevalence rates of hypothyroidism [27.78% vs. 1.14%; odds ratio (OR) = 33.07; 95% confidence interval (CI): 7.10-153.70] and bipolar spectrum disorders (16.67% vs. 0.2%; OR = 138.4; 95% CI: 36.40-526.43) compared to control populations (p < 0.0001 for both). Similarly, individuals screening positive for depressive symptoms (PHQ9 > 9) showed markedly increased odds (55.5% vs. 4.16%; OR = 28.75; 95% CI: 6.52-126.73).

CONCLUSION: The findings suggest that hypothyroidism and bipolar spectrum disorders may act as predisposing factors in the development of CFS/ME in long-term COVID-19. Identifying these clinical antecedents could facilitate early detection and the development of targeted intervention strategies in at-risk populations.

RevDate: 2025-09-15

Santo K, Favaro L, E Martins (2025)

Following the Pandemic: Exploring Long COVID's impact on Global Health through the World Heart Federation Global COVID-19 Study.

Global heart, 20(1):79.

Although the COVID-19 pandemic crisis has come to an end, Long COVID continues to pose a profound challenge to global health. Based on findings from the World Heart Federation (WHF) Global COVID-19 Study, an international prospective cohort study, this editorial reflects on the enduring burden of symptoms and complications among 2,535 previously hospitalized patients across 16 countries during the Omicron era. Beyond a mortality rate of 15% and clinical manifestations such as fatigue, dyspnea, and adverse cardiovascular events, the study highlighted substantial psychosocial and socioeconomic impacts, with reduced work capacity and functional limitations particularly affecting populations in low- and middle-income countries captured through EuroQol 5-dimension scale and employment data. These findings emphasize that the burden of Long COVID extends beyond individual health, with significant implications for healthcare systems and economic stability. Addressing this challenge requires ongoing multidisciplinary research, validated diagnostic criteria, novel biomarkers, and effective preventive and therapeutic strategies. Furthermore, decentralized monitoring models-exemplified by telephone-based data collection in the WHF study-may offer scalable approaches to improve surveillance and inform global health policies for current and future public health crises.

RevDate: 2025-09-15
CmpDate: 2025-09-15

Liu C, Liu C, Yan R, et al (2025)

Association of COVID vaccinations and treatments with long COVID beyond 6 months: a case-control study on the adult population in a large integrated healthcare system in the United States from 2020 to 2023.

Preventive medicine reports, 57:103188.

OBJECTIVE: Long coronavirus disease (Long COVID) is a chronic condition causing significant long-term disability and economic burden. This study aims to measure the association between COVID vaccinations and treatment at the time of acute infection with Long COVID outcomes beyond six months post-infection, controlling for demographic and medical variables.

METHODS: This retrospective case-control study used electronic medical records from Kaiser Permanente Southern California to evaluate Long COVID outcomes from January 2022 to June 2023 with vaccination doses and nirmatrelvir/ritonavir, and from October 2020 to June 2023 with remdesivir and other treatments. Statistical analysis used univariate chi-square and Kruskal-Wallis tests and conditional logistic regression.

RESULTS: Our study had 840 (January 2022 analysis) and 2632 (October 2020 analysis) Long COVID patients diagnosed by International Classification of Diseases-10 code at least 6 months after acute COVID infection with 1:5 matched controls by age, sex, race/ethnicity, Body Mass Index, and date of acute COVID infection. Long COVID outcome was inversely associated with the number of COVID vaccination doses (one dose odds ratio (OR) 0.77; 95 % CI 0.63-0.96, two doses OR 0.73; 95 % CI 0.59-0.92, three doses OR 0.64; 95 % CI 0.44-1.00, four doses OR 0.29; 95 % CI 0.06-1.49) and nirmatrelvir/ritonavir (OR 0.05; 95 % CI 0.04-0.07) or remdesivir (OR 0.31; 95 % CI 0.19-0.49) treatment with no interaction between three vaccinations with nirmatrelvir/ritonavir and four vaccinations with remdesivir treatment.

CONCLUSION: These findings may influence existing clinical practices for vaccination and antiviral treatment strategies to decrease Long COVID consequences.

RevDate: 2025-09-15

Brode WM, Posada J, D Nagireddy (2025)

Ketamine as a Potential Neuromodulatory Treatment for Long COVID Neuropsychiatric and Neuropathic Symptoms: A Case Report.

Journal of clinical psychopharmacology [Epub ahead of print].

RevDate: 2025-09-14

Liira H, Varonen M, Venäläinen MS, et al (2025)

Associations of socioeconomic status and health-related quality of life in patients with long COVID and patients with persistent physical symptoms: A comparison of two cohort studies at baseline.

Journal of psychosomatic research, 197:112374 pii:S0022-3999(25)00338-1 [Epub ahead of print].

BACKGROUND AND AIM: Emerging evidence suggest a significant association between Long COVID (LC) and other persistent physical symptoms (PPS) with lower socioeconomic status (SES). We investigated the relationship between SES and health-related quality of life (HRQOL), as measured by the 15D and the EUROHIS-QOL-8 instruments, among patients with LC and those experiencing other PPS-related conditions.

METHODS: Factors related to clinical and socioeconomic aspects that affect HRQOL were evaluated using 15D, a validated 15-item self-reported questionnaire. Two parallel cohorts at Helsinki University Hospital were analyzed: the Helsinki LC cohort (n = 422; 2021-2023) and the Helsinki Sympa cohort (n = 599; 2020-2024), consisting of patients with PPS. Additionally, we performed an intersectional MAIHDA analysis of biopsychosocial predictors of quality of life.

RESULTS: The cohorts were demographically similar, with 70.6 % and 66.4 % female participants and mean ages of 44.8 years (SD = 11.3) and 38.8 years (SD = 11.0) in the LC and Sympa cohorts, respectively. By EUROHIS-QOL-8, 34 % of LC and 41 % of Sympa respondents rated their overall QOL as very bad or bad (scale options 1-2 out of 5). Mean 15D scores were 0.76 (SD = 0.11) in the LC cohort and 0.74 (SD = 0.11) in the Sympa cohort (scale: 0-1). Working status, comorbidities, and tertiary education emerged as key determinants in the information-criteria-based model, highlighting the cumulative burden of overlapping social and clinical disadvantages. No significant multiplicative effects were found within our cohorts.

CONCLUSIONS: Patients in both cohorts reported reduced HRQOL, and the influence of socioeconomic factors on QOL were highly similar. Comorbidities, only basic school education, and being out of work were associated with the lowest HRQOL scores. The accumulation of socioeconomic disadvantage may function as a barrier to treatment, and healthcare professionals should recognize these challenges and ensure that patients receive adequate support.

RevDate: 2025-09-13

Yamada G, Itaya T, Iwamoto N, et al (2025)

Development and Validation of a Simple 11-item Long COVID Burden Index (LCBI).

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy pii:S1341-321X(25)00206-5 [Epub ahead of print].

BACKGROUND: Existing patient-reported outcome measures for long COVID are comprehensive; however, they are time-consuming and burdensome for some patients in daily practice.

OBJECTIVES: This study aimed to develop and validate a simple patient-reported outcome measure to assess the burden associated with frequently occurring symptoms in patients with long COVID.

METHODS: Following an extensive literature review, a questionnaire consisting of 11 items was developed based on the modified Delphi method with an expert panel. Its face validity was assessed in three individuals with COVID-19 history. The study subjects were Japanese residents who responded to the online QoLCoVE (Quality of Life in the COVID-19 Era) study between March 8 and April 1, 2024. The known-group and concurrent validity were assessed after exploratory factor analysis. The internal consistency was evaluated using Cronbach's alpha.

RESULTS: A total of 1,014 participants were included in the analysis, all at least two months after their last COVID-19 infection. The factor analysis results showed unidimensionality. Internal consistency reliability assessed using Cronbach's alpha was 0.89. For known-group validity, the total score decreased with time since the acute COVID-19 infection, as well as with more frequent vaccinations, and increased with an increasing previous history of COVID-19. A dose-dependent relationship was observed between EQ-5D-5L and the scale's total score, categorized according to quartiles.

CONCLUSION: We successfully developed the Long COVID Burden Index, a simple 11-item scale to easily quantify symptoms frequently experienced by patients with long COVID, which may interfere with their daily lives.

RevDate: 2025-09-13

Yong SJ, Kenny TA, Halim A, et al (2025)

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.

Reviews in medical virology, 35(5):e70070.

With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.

RevDate: 2025-09-13

Christensen JFMM, Meyer R, Holmqvist M, et al (2025)

Cognitive sequelae in post-COVID-syndrome: a Danish-Swedish case-control study.

Infectious diseases (London, England) [Epub ahead of print].

BACKGROUND: While patients with post-COVID syndrome (PCS) suffer from cognitive deficits few studies directly compare patients with PCS to subjects recovered after an infection with the 'Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)'.

OBJECTIVES: To investigate cognitive performance adjusting for age, increasing body-mass-index (BMI), smoking, years of education, gender and hospitalisation while infected in patients with PCS compared to controls fully recovered. Secondly, to stratify cognitive performance based on the SARS-CoV-2 virus strain (variant of concern 'VOC') causing the infection. Thirdly, to assess whether patients with PCS have increased levels of psychological distress and affected hand grip strength as both are associated with cognitive performance.

METHODS: A Danish-Swedish case-control study we recruited adult patients (18-75 years) with PCS from long-COVID outpatient clinics in Region Zealand Denmark and Skåne County Sweden. Participants had confirmed SARS-CoV-2 infection >12 weeks prior to inclusion and healthy control subjects had recovered completely. All study participants were exposed to cognitive tests, Kessler's psychological distress scale (K10) and tested with a hand-dynamometer.

RESULTS: Recruiting 181 cases and 155 control subjects, patients with PCS had reduced cognitive performance scores on all domains though hardly clinically significant. Reduced processing speed was impacted the most with patients infected early in the pandemic exhibiting greater deficits.

CONCLUSION: PCS was associated with reduced cognitive processing speed compared to fully recovered controls with those infected early in the pandemic having greater deficits. Psychological distress and hand grip strength were affected in patients with PCS, but not decisively associated with cognitive performance.

RevDate: 2025-09-13

Hansel Robinson J, Bakir H, James AS, et al (2025)

Prevalence, Severity, Concomitant Factors, and Natural Trajectory of Insomnia in Patients with Long COVID.

Journal of clinical medicine, 14(17): pii:jcm14176114.

Background/Objective: Insomnia is a clinically important symptom in Long COVID; however, few studies have addressed the presentation and course of insomnia symptoms in patients with Long COVID. Methods: The Insomnia Severity Index (ISI) was administered as part of a comprehensive baseline neuropsychological evaluation (Time 1) for patients with Long COVID at an Academic Medical Center (AMC). Data were gathered on 172 consecutively referred patients between the dates of November 2020 and May 2022. The mean age of patients at Time 1 was 49 years (range: 18 to 78), with a mean of 15 years of education. Patients were 70% female and 30% male and identified as White/Caucasian (78%), Black/African American (21%), or American Indian (1%). Patients' severity of COVID-19 infection and self-reported emotional, somatic, cognitive, and fatigue symptoms were also gathered to identify concomitant risk factors for insomnia in Long COVID. Patients were then followed to observe the natural trajectory of insomnia complaints in Long COVID, with the Time 2 evaluation a mean of 9 months after the Time 1 evaluation. Results: Seventy-eight percent of Long COVID patients reported insomnia symptoms at Time 1, with 30% reporting Subthreshold Insomnia symptoms (ISI Score = 8-14), 30% reporting Moderate Insomnia symptoms (ISI Score = 15-21), and 18% reporting Severe Clinical Insomnia (ISI Score = 22-28). Severity of acute COVID-19 infection was not correlated with severity of insomnia in Long COVID; however, being non-white (r = 0.24, n = 172, p < 0.01) and having higher self-reported levels of anxiety (r = 0.41, n = 172, p < 0.01), depression (r = 0.52, n = 172, p < 0.01), perceived stress (r = 0.38, n = 172, p < 0.01), somatic symptoms (r = 0.51, n = 172, p < 0.01), cognitive failures, and fatigue were significantly correlated with insomnia symptoms. Insomnia was also significantly correlated with lower global cognitive function (r = 0.51, n = 172, p < 0.01) and lower cognitive flexibility (r = -0.17, n = 172, p < 0.05). There was a statistically significant decrease in reported ISI scores from Time 1 to Time 2 (t = -3.04; p = 0.003); however, ISI mean scores at both Time 1 (ISI Score = 14) and Time 2 (ISI Score = 12) remained in the Subthreshold Insomnia range (ISI score 8-14). Conclusions: Findings suggest that a large majority of Long COVID patients experience insomnia symptoms. Additionally, insomnia symptoms did not dissipate over time in a clinically meaningful way and were highly correlated with reduced global cognitive function, reduced cognitive flexibility, and higher levels of reported mood symptoms, fatigue, somatic symptoms, and experience of cognitive failures. Thus, there is a pressing need for intervention strategies to treat insomnia in Long COVID patients.

RevDate: 2025-09-13

Zissler UM, Poehlmann T, Gloeckl R, et al (2025)

Acute Effects of Osteopathic Treatment in Long COVID-19 Patients with Fatigue Symptoms: A Randomized, Controlled Trial.

Journal of clinical medicine, 14(17): pii:jcm14176066.

Background: Persistent fatigue is among the most commonly reported symptoms in patients suffering from post-acute sequelae of SARS-CoV-2 infection (long COVID). Autonomic dysfunction, measurable via heart rate variability, has been implicated as a contributing factor. Osteopathic manipulative treatment is a manual therapeutic approach that targets autonomic balance and may offer a novel intervention for long COVID-related fatigue. Methods: In this single-blind, randomized controlled trial, 42 participants (mean age 51 ± 11 years; fatigue severity score: 31 ± 5 points) with long COVID and persistent fatigue ≥12 weeks post-infection were allocated to either a 45 min standardized osteopathic treatment (n = 21) or a sham-treatment group (n = 21). Heart rate variability was assessed using a 10 min resting electrocardiogram before intervention, immediately after, and again 48 h later. The analysis of heart rate variability encompassed time-domain indices, including the root mean square of successive differences, the standard deviation of normal-to-normal intervals, mean heart rate, and mean RR interval. Additionally, frequency-domain measures such as low-frequency, high-frequency, total power, and the LF/HF ratio were considered. Results: The osteopathy group showed a statistically significant increase in root mean square of successive differences post-treatment (p < 0.01), accompanied by a decrease in the stress index (p < 0.05) and an increase in the mean of the standard deviations of RR intervals (p < 0.05). Significant between-group differences were observed for mean heart rate and mean of RR intervals (p < 0.05). Frequency-domain measures also improved significantly from baseline in the intervention group. Outlier patterns suggest potential subgroup effects, possibly due to underlying dysautonomia. Conclusions: A single session of osteopathic treatment significantly enhanced short-term heart rate variability in long COVID patients with fatigue. These findings highlight the potential role of manual autonomic modulation as a supportive therapy in long COVID management. Further research is needed to assess the long-term effects and optimal treatment frequency of osteopathic manipulative treatment in this population.

RevDate: 2025-09-13

Han E, Hasimbegovic E, Schönbauer R, et al (2025)

Combined Cardiac Arrhythmias Leading to Electrical Chaos Developed in the Convalescent Phase of SARS-CoV-2 Infection: A Case Report and Literature Review.

Journal of clinical medicine, 14(17): pii:jcm14176053.

Background: Acute SARS-CoV-2 infection may induce cardiac arrhythmias associated with viral myocarditis, which typically disappear in the convalescent phase after healing of the myocardial inflammation. Methods: We report the case of a 37-year-old woman with a childhood history of atrial septal defect repair and stable normofrequent atrial rhythm, who presented two months post-COVID-19 with palpitations and dizziness. Diagnostic evaluation included cardiac magnetic resonance imaging (CMR), 24 h Holter electrocardiogram (ECG) monitoring, and laboratory assessments over a 3-year period. Results: CMR suggested subacute myocarditis, and Holter ECG revealed multiple discernible complex cardiac arrhythmias including atrial bradycardia, intermittent junctional rhythm (JR), atrial fibrillation (AF), and non-sustained ventricular tachycardia. Laboratory results showed a moderate but transient increase in lactate dehydrogenase, persistently mildly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and immunoglobulin A (IgA), with all other cardiac, inflammatory, immunologic, and organ function parameters remaining normal. In spite of chaotic cardiac rhythm with alternating JR, AF, and atrial normofrequent rhythm with frequent blocked supraventricular beats and increasing atrioventricular conduction time, no therapeutic intervention was necessary during follow-up, and a conservative treatment approach was agreed with the patient. Two years post-COVID-19 infection, the patient returned to a normofrequent atrial rhythm with a markedly prolonged PQ time (500 ms) and a different P wave morphology compared to pre-COVID, without other rhythm disturbances. Conclusions: This case demonstrates a rare pattern of post-viral arrhythmias first emerging in the convalescent phase and resolving spontaneously after two years. It underscores the need for long-term rhythm surveillance following COVID-19, even in patients with prior structural heart disease and a stable baseline rhythm.

RevDate: 2025-09-13

Var SR, Maeser N, Blake J, et al (2025)

Pulmonary and Immune Dysfunction in Pediatric Long COVID: A Case Study Evaluating the Utility of ChatGPT-4 for Analyzing Scientific Articles.

Journal of clinical medicine, 14(17): pii:jcm14176011.

Coronavirus disease 2019 (COVID-19) in adults is well characterized and associated with multisystem dysfunction. A subset of patients develop post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID), marked by persistent and fluctuating organ system abnormalities. In children, distinct clinical and pathophysiological features of COVID-19 and long COVID are increasingly recognized, though knowledge remains limited relative to adults. The exponential expansion of the COVID-19 literature has made comprehensive appraisal by individual researchers increasingly unfeasible, highlighting the need for new approaches to evidence synthesis. Large language models (LLMs) such as the Generative Pre-trained Transformer (GPT) can process vast amounts of text, offering potential utility in this domain. Earlier versions of GPT, however, have been prone to generating fabricated references or misrepresentations of primary data. To evaluate the potential of more advanced models, we systematically applied GPT-4 to summarize studies on pediatric long COVID published between January 2022 and January 2025. Articles were identified in PubMed, and full-text PDFs were retrieved from publishers. GPT-4-generated summaries were cross-checked against the results sections of the original reports to ensure accuracy before incorporation into a structured review framework. This methodology demonstrates how LLMs may augment traditional literature review by improving efficiency and coverage in rapidly evolving fields, provided that outputs are subjected to rigorous human verification.

RevDate: 2025-09-13

Barilli A, Visigalli R, Recchia Luciani G, et al (2025)

Baricitinib and Infliximab Mitigate the Endothelial-to-Mesenchymal Transition (EndMT) Induced by Cytokines in HUVECs.

International journal of molecular sciences, 26(17): pii:ijms26178672.

Endothelial-to-mesenchymal transition (EndMT) is associated with various pathologies including cardiovascular, inflammatory, and fibrotic diseases or neoplasia. Concerning COVID-19, multiple organ dysfunctions and long COVID syndrome are mediated by microvascular damage and, recently, the role of SARS-CoV-2 peptide fragments in the induction of EndMT was demonstrated. Here, we investigated the immune-mediated effects of Spike S1 of SARS-CoV-2 on EndMT and demonstrated that cytokines secreted by S1-activated macrophages, mainly TNFα + IFNγ, also induce the phenotypical switch in HUVECs. In particular, a loss of the typical cobblestone morphology is observed, along with a huge reduction in endothelial adhesion molecules, such as vWF, CD31, and VE-cadherin, and a concomitant acquisition of mesenchymal markers, such as N-cadherin and FSP1 protein. In addition, the combined use of the drug infliximab, targeting TNFα, and baricitinib, an inhibitor of the JAK-STAT pathway, hinders the phenotypical changes by restoring the proper expression of endothelial markers. The protective effect of these drugs is evident not only when they are added to the culture medium together with the trigger, but also when added later, i.e., once EndMT has been started. These findings reinforce the role of COVID-19-associated cytokine storm in endothelial dysfunction and in the onset of the fibrotic process and sustain the clinical relevance of infliximab and baricitinib for the prevention of vascular damage.

RevDate: 2025-09-13

Padkao T, Intakhiao S, Prakobkaew N, et al (2025)

Anti-Inflammatory and Antioxidant Effects of HIIT in Individuals with Long COVID: Insights into the Potential Role of Triphala.

International journal of molecular sciences, 26(17): pii:ijms26178623.

Long COVID is characterized by persistent symptoms associated with chronic inflammation and oxidative stress. While high-intensity interval training (HIIT) and supplementation with antioxidants such as Triphala have demonstrated individual therapeutic benefits, their combined effects remain unclear. This study aimed primarily to evaluate the effects of an 8-week HIIT program on markers of inflammation, oxidative stress, and exercise-related symptoms in individuals with long COVID, and secondarily to explore whether Triphala supplementation provided additional benefits. A total of 104 participants (aged 18-59 years) were randomized into three groups-control (placebo), HIIT (cycling for 28 min/day, 3 days/week), and combined (HIIT + Triphala, 1000 mg/day)-for 8 weeks. The biomarkers assessed included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), protein carbonyls, and superoxide dismutase (SOD) activity. Following the intervention, significant reductions in IFN-γ, TNF-α, MDA, protein carbonyls, and rating of perceived exertion were observed in both the HIIT and combined groups (p < 0.05), with no significant differences between the two. SOD activity significantly increased in all groups, including the control group (p < 0.05), with no between-group differences. An 8-week HIIT program appears to be effective in reducing inflammation, oxidative stress, and dyspnea in individuals with long COVID. Triphala supplementation did not provide any additional statistically significant benefit but was safe and well tolerated.

RevDate: 2025-09-13

Korobova ZR, Arsentieva NA, Lyubimova NE, et al (2025)

Redefining Normal: Cytokine Dysregulation in Long COVID and the Post-Pandemic Healthy Donors.

International journal of molecular sciences, 26(17): pii:ijms26178432.

The COVID-19 pandemic has caused over 7 million deaths, but its legacy extends beyond mortality. SARS-CoV-2 infection induces immune alterations that persist post-recovery, manifesting not only in long COVID (LC) but also in healthy individuals. Cytokines serve as critical orchestrators of these processes. The goal of this study is to investigate post-pandemic immune remodeling through cytokine assessment in both patients with LC and healthy donor, and to compare the post-pandemic population with pre-pandemic controls to find changes in the immune responses and cytokine profiles. A panel of 47 immune mediators (cytokines, chemokines, and growth factors) was measured with the MAGPIX multiplex analysis. LC was characterized by an increase in IL-7, IL-8, IL-17F, IL-18, EGF, FGF-2, PDGF-AA, sCD40L, and MCP-3 and a decrease in IL-4, IL-13, IL-22, IL-27, and FLT-3L. Comparing post-pandemic recovered individuals with pre-pandemic healthy cohort, we saw an upregulation of IL-13 and MCP-3 and a downregulation of MDC, M-CSF, IL-12, and IL-17F. While LC is characterized by persistent immune imbalance-particularly in cytokine networks-our data emphasize the critical need to study healthy donors in both pre- and post-pandemic eras when analyzing and interpreting these changes.

RevDate: 2025-09-12

Chadalavada S, Salih A, Naderi H, et al (2025)

Prospective electrocardiographic and cardiovascular magnetic resonance alterations in the UK Biobank COVID-19 repeat imaging study.

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance pii:S1097-6647(25)00119-X [Epub ahead of print].

BACKGROUND: Cardiovascular magnetic resonance (CMR) and electrocardiographic (ECG) abnormalities after COVID-19 are widely reported. However, the absence of pre-infection assessments limits causal inference from these studies. This study aims to compare interval change in CMR and ECG measures in participants with incident COVID-19 and matched uninfected controls in UK Biobank.

METHODS: UK Biobank participants with documented COVID-19 who had CMR and ECG performed prior to the pandemic were invited for repeat assessment, along with uninfected participants matched on age, sex, ethnicity, location, and date of baseline imaging. Automated pipelines were used to extract ECG phenotypes and CMR measures of cardiac structure and function, aortic distensibility, aortic flow, and myocardial native T1. Logistic regression was used to examine associations of baseline metrics with incident COVID-19. Standardized residual approach was used to compare the degree of interval change in CMR and ECG metrics between cases and controls.

RESULTS: We analyzed 2,092 participants (1,079 cases, 1,013 controls) with average age of 60±7 years. 47% were male. There was 3.2±1.5 years between pre- and post-infection assessments. 4% of cases were hospitalized. Lower baseline left ventricular ejection fraction and worse longitudinal, circumferential, and radial strain were associated with higher risk of incident COVID-19. There were no significant differences in interval change of any CMR or ECG metric between cases and controls.

CONCLUSIONS: While pre-existing cardiovascular abnormalities are linked to higher risk of COVID-19, exposure to infection does not alter interval change of highly sensitive CMR and ECG indicators of cardiovascular health.

RevDate: 2025-09-12

Yang X, Shen Y, Tang B, et al (2025)

Multi-omics blood atlas reveals host immune response features of immunocompromised populations following SARS-CoV-2 infection.

Molecular & cellular proteomics : MCP pii:S1535-9476(25)00167-7 [Epub ahead of print].

The dysregulation of human genes and proteins following SARS-CoV-2 infection significantly impacts the clinical symptoms and prognosis of COVID-19, particularly in immunocompromised individuals such as hematological tumor patients. Despite this, a comprehensive multi-omics understanding of human host immune responses remains incomplete. Here, we conducted a multi-omics analysis of 89 peripheral blood samples (RNA sequencing) and 98 serum samples (proteome mass spectrometry) from 52 COVID-19 patients, including hematological tumor patients and non-tumor individuals. By integrating transcriptomic, proteomic, and interactome data, we compared differentially expressed genes (DEGs) and proteins (DEPs) across infection stages and clinical outcomes to gain insights into the mechanisms of SARS-CoV-2 infection. Our analysis revealed distinct and overlapping transcriptomic and proteomic responses to SARS-CoV-2 infection. DEGs were predominantly associated with innate immune responses and viral processes, while DEPs were linked to actin cytoskeleton organization and protein kinase regulation. Notably, DEGs and DEPs often exhibited opposing regulatory patterns, suggesting post-transcriptional and post-translational mechanisms. Tumor patients showed more severe proteomic perturbations, with a higher proportion of DEPs functioning as key hub proteins in cellular networks. Network-based drug repositioning identified potential therapeutic targets, including HSPA8, SRC, STAT1, APOE, and APP. Clinical analysis indicated that long COVID patients experienced more severe coagulation abnormalities, immunosuppression, and myocardial injury, while acutely deceased patients exhibited abnormally activated immune responses. Our study provides a comprehensive resource for understanding the molecular mechanisms of SARS-CoV-2 infection in hematological tumor patients. By integrating multi-omics data, we highlight the importance of proteomic changes in disease progression and identify potential therapeutic targets for COVID-19 and long COVID.

RevDate: 2025-09-12

Anonymous (2025)

Correction to "Symptoms and Risk Factors for Long Covid: A Cross-Sectional Study In Primary Care".

Journal of medical virology, 97(9):e70609.

RevDate: 2025-09-12

Paranhos ACM, Dias ARN, Mendes EAR, et al (2025)

Persistent olfactory dysfunction as an indicator of cognitive impairment in long COVID-19 syndrome: implications for monitoring and rehabilitation.

European archives of psychiatry and clinical neuroscience [Epub ahead of print].

BACKGROUND: Persistent olfactory dysfunction (OD) and cognitive impairment are among the most frequently reported sequelae of long term infection with SARS-CoV-2 (long COVID-19). However, the association between these conditions remains unclear. This study investigated the correlation between OD and cognitive impairment in patients recovering from COVID-19 to identify the implications for therapeutic and rehabilitation strategies.

MATERIALS AND METHODS: A cross-sectional study of adult patients diagnosed with long COVID was conducted at a healthcare centre in Brazil. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Centre (CCCRC) test, and cognitive performance was evaluated using the Montreal Cognitive Assessment (MoCA). Statistical analyses included odds ratios (OR) and linear regression to explore the association between OD severity and cognitive scores, adjusting for potential confounders such as age, sex, and comorbidities.

RESULTS: A total of 241 patients (age: 48.60 ± 12.68 years; 73% female) were included. Cognitive impairment (MoCA < 23) was present in 64% of the participants. OD was identified in 92% of the patients and ranged from mild to anosmia. Linear regression analysis showed a weak yet statistically significant correlation between the CCCRC and MoCA scores (R = 0.14, p = 0.02). An OR of 2.87 (95% CI: 1.57-5.25, p = 0.00) indicated higher odds of cognitive impairment in patients with severe OD.

DISCUSSION: This study supports the hypothesis that there is a weak yet significant association between OD and cognitive impairment in patients with long COVID. These findings underscore the importance of early screening for olfactory dysfunction as a potential marker of cognitive monitoring and the need for intervention in this population.

RevDate: 2025-09-12

Altermatt A, Wilkinson AL, Heath K, et al (2025)

Well-being among people with long and short COVID: a serial cross-sectional study in Victoria, Australia.

BMJ public health, 3(2):e002062.

BACKGROUND: It is critical to disseminate all evidence on long COVID's impact on people's lives to inform policy and practice. We aimed to assess five measures of well-being, before and after SARS-CoV-2 infection between people with long COVID (defined as symptoms lasting more than 1 month) and people with short COVID (defined as symptoms resolving within 1 month).

METHODS: Participants from the Optimise Study, a longitudinal cohort study in Victoria, Australia (September 2020-August 2022), had self-reported history of SARS-CoV-2 infection and self-reported long COVID status. Serial cross-sectional analysis compared participants with long and short COVID on Personal Well-being Index, number of COVID-19-like symptoms experienced, number of days exercised and frequency of experiencing positive and negative emotions.

RESULTS: 217 participants were included, aged 20-86 years (median age 43, IQR: 31-57), 75% women. Compared with those with short COVID, participants with long COVID had lower well-being before (mean difference (MD)=-8.3, 95% CI (-14.7, -2.0), p-adjusted=0.07), during (MD=-10.3, 95% CI (-16.5, -4.0), p-adjusted=0.03) and after (MD=-9.91, 95% CI (-16.71, -3.11), p-adjusted=0.05) infection and experienced more COVID-19-like symptoms during infection (MD=1.72 (0.72, 2.72), p-adjusted=0.03). In December 2022, 71% (40/56) reported difficulty performing tasks in the past 4 weeks.

CONCLUSION: On average, we observed lower well-being among participants with long COVID, including before SARS-CoV-2 infection, suggesting an underlying difference in well-being between groups. Long COVID continued to impact physical functioning, but ongoing changes were not detected by personal well-being scales.

RevDate: 2025-09-11

Steenblock C, Walther R, Kok Y, et al (2025)

Single-Center Study of Therapeutic Apheresis in 24 Male Patients from the MENA Region: Reduction of Lipids, Inflammatory Markers, Autoantibodies, and Implications for Fatigue, Genetics, and Aging.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme [Epub ahead of print].

Cardiovascular and metabolic disorders, particularly diabetes and obesity, are highly prevalent in the Middle East and North Africa (MENA) region, exhibiting some of the highest global incidence rates. These conditions significantly increase the severity of infectious diseases, notably COVID-19, leading to a rise in long-COVID cases among affected individuals. Furthermore, the MENA region's extreme temperatures exacerbate cardiovascular issues by elevating heart rates and blood pressure, increasing dehydration and blood viscosity. Extracorporeal therapies, such as apheresis, effectively reduces plasma lipids and inflammatory markers. Furthermore, apheresis has shown promise in reducing autoantibodies associated to long-COVID. Our previous research indicated that apheresis alleviates symptoms in patients with long-COVID and chronic fatigue syndrome. In this study, we treated 24 male patients from the MENA region suffering from chronic fatigue and/or different metabolic diseases such as diabetes, dyslipidemia, or obesity, using double filtration plasmapheresis. Comprehensive plasma analyses were performed before and after apheresis to assess lipid profiles, inflammatory markers, and autoantibodies, revealing significant changes following the procedure. Genetic analyses on a subgroup of the patients showed no mutations in the LDLR, APOB, APOE, PCSK9, LIPA, and LDLRAP1 genes known to be associated with predispositions to monogenic lipid disorders. However, all patients in this subgroup demonstrated an intermediate to high likelihood that their elevated lipid levels have a polygenic basis. These findings suggest that implementing apheresis in the MENA region could significantly improve health outcomes and life expectancy for affected individuals.

RevDate: 2025-09-11

Wilhelm F, Cadamuro J, S Mink (2025)

Autoantibodies in long COVID: a systematic review.

The Lancet. Infectious diseases pii:S1473-3099(25)00411-6 [Epub ahead of print].

Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers. This systematic review synthesises current evidence on the association between autoantibodies and long COVID, with the goal of evaluating their prognostic and diagnostic utility. Studies published in the PubMed and MEDLINE databases between Jan 1, 2020, and June 10, 2025, were considered. Study selection and quality assessment were done independently by two researchers. Of the 1113 publications screened, 44 studies met the inclusion criteria, with a total of 7571 participants, including 3372 individuals with long COVID. 31 (71%) studies reported an association between autoantibodies and long COVID; however, there was substantial heterogeneity in study design, type and timing of antibody measurements, and long COVID definitions. Several autoantibodies have been associated with long COVID occurrence, symptoms, and severity. Antinuclear antibodies, and autoantibodies targeting G protein-coupled receptors and chemokines, have emerged as potential biomarkers for aiding in the diagnosis, prognosis, and assessment of disease severity in long COVID. However, larger studies are needed to confirm the diagnostic and prognostic utility of these autoantibodies in the context of long COVID.

RevDate: 2025-09-11

Gutiérrez-Martínez L, Reynolds WC, Abril I, et al (2025)

Sleep quality and efficiency in adults with post-acute sequelae of COVID-19.

Sleep advances : a journal of the Sleep Research Society, 6(3):zpaf051 pii:zpaf051.

STUDY OBJECTIVES: Sleep disruptions are associated with adverse mental and physical health outcomes. Individuals with post-acute sequelae of COVID-19 (PASC) commonly report worsened sleep. This study examined sleep quality and efficiency and their associations with neuropsychiatric symptoms and fatigue in non-hospitalized individuals with PASC.

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

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

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

RevDate: 2025-09-11

Becker JH, Li J, Lin JJ, et al (2025)

Neurocognitive trajectories in long COVID: Evidence from longitudinal analyses.

Brain, behavior, & immunity - health, 48:101093 pii:S2666-3546(25)00151-6.

BACKGROUND: Patients frequently report symptoms of cognitive impairment or "brain fog" after acute COVID-19 infection, but the trajectory of these symptoms over time has yet to be determined. We assessed cognitive function over a 42-month period after acute SARS-CoV-2 infection and identified factors associated with the trajectory of cognitive function over this period.

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

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

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

RevDate: 2025-09-11

Lee SP, SY Kang (2025)

Clinical outcomes of persistent cough following coronavirus disease 2019 infection: A 1-year retrospective cohort study.

Asia Pacific allergy, 15(3):186-191.

BACKGROUND: Cough is one of the multiple prolonged symptoms observed in patients who had coronavirus disease 2019 (COVID-19) infection.

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

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

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

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

RevDate: 2025-09-11

Cooper E, Lound A, Jones K, et al (2025)

Challenges of Inclusion: A Population-Based Interview Study of Long Covid.

Health expectations : an international journal of public participation in health care and health policy, 28(5):e70428.

INTRODUCTION: People with long Covid report a wide range of symptoms and inconsistent responses when seeking clinical diagnosis and support. Much of the qualitative research on long Covid has been based on people attending specialist clinical services or who have accessed support groups. We aimed to understand the varied experiences of persistent symptoms following Covid-19 and the impact on the lives of people affected.

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

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

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

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

RevDate: 2025-09-11

Gustavsson E, Johnson E, R Levi (2025)

Towards a Less Ideal Theory About Well-being-The Case of Post COVID Condition.

Journal of bioethical inquiry [Epub ahead of print].

Post COVID-19 Condition (PCC) is a complex condition presenting significant challenges for patients. Individuals suffering from severe PCC are often assessed in rehabilitation medicine departments or specialized post-COVID centres, where their condition is evaluated using the International Classification of Functioning, Disability and Health (ICF). The ICF framework primarily focuses on functional impairments, disabilities, and restrictions in participation, with an emphasis on the concept of "functioning." However, a critical question remains: how does this notion of functioning relate to the well-being of these individuals? This paper explores this issue by examining three fictionalized but typical case studies of PCC patients in relation to two distinct theoretical approaches. First, we engage with theories about well-being from the philosophy of well-being emphasizing the individual's perspective. Second, we explore relational approaches in bioethics and their theoretical underpinnings, which emphasize how people are situated, considering context and relations rather than purely individual conditions. The paper highlights the potential tensions between these approaches while arguing that a more comprehensive understanding of well-being can emerge by integrating insights from both traditions. Through the examination of PCC patient cases, we propose that well-being can be better understood when approached from multiple angles, enriching the understanding of patient outcomes in rehabilitation medicine.

RevDate: 2025-09-11

Crevenna R, M Keilani (2025)

Correction to: Authors' response to the letter to the editor 'Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue'.

RevDate: 2025-09-11

Crevenna R, M Keilani (2025)

Authors' response to the letter to the editor "Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue".

RevDate: 2025-09-10

Walker TA, Kohler JZ, MM Haddad (2025)

Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management.

Brain, behavior, and immunity pii:S0889-1591(25)00350-2 [Epub ahead of print].

RevDate: 2025-09-10

Sandoval MN, Moore LW, Huang HJ, et al (2025)

Long COVID risk factors and outcomes among solid organ transplant recipients: a retrospective cohort study.

Frontiers in surgery, 12:1602167.

BACKGROUND: Solid organ transplant (SOT) recipients are not only at increased risk of morbidity and mortality due to acute COVID-19 but may also experience poor long-term outcomes due to post-acute COVID-19 syndromes, including long COVID.

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

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

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

RevDate: 2025-09-10

Leitner M, Paletta L, Leal-Garcia M, et al (2025)

A tablet-based intervention study to alleviate cognitive and psychological symptoms in patients with post-Covid-19 condition.

Frontiers in psychology, 16:1582742.

BACKGROUND: Cognitive impairment and psychological complaints are among the most common consequences for patients suffering from Post-Covid-19 condition (PCC). As there are limited training options available, this study examined a longitudinal tablet-based training program addressing cognitive and psychological symptoms.

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

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

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

RevDate: 2025-09-10

Ferreira LGJ, da Silva Almeida I, Costa RR, et al (2025)

Long COVID-19 alters muscle architecture and muscle-tendon force transmission: a one-year longitudinal study.

Frontiers in physiology, 16:1641046.

INTRODUCTION: There are limited studies on the long-term effects of COVID-19 on skeletal muscle morphology and architecture. Therefore, this study aims to address this gap by assessing the effects of prior COVID-19 infection on quadriceps muscle architecture and tendon-aponeurosis complex (TAC) properties over a one-year period, comparing three cohorts: individuals with moderate COVID-19, individuals with severe COVID-19, and a healthy control group.

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

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

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

RevDate: 2025-09-10

Pienkos S, Swank Z, Hamlin RE, et al (2025)

Single-Cell and Plasma Proteomics Do Not Differentiate Patients With and Without SARS-CoV-2 Antigenemia in Convalescence in a Cohort of 100 Patients.

Open forum infectious diseases, 12(9):ofaf515.

Plasma samples obtained approximately 3 (n = 100) and 12 months (n = 78) after acute SARS-CoV-2 infection were tested for S1, spike, and N antigens. There were no significant differences in plasma proteins or single-cell protein expression levels on immune cells between those with and without plasma antigen detected.

RevDate: 2025-09-09

Fazekas C, Goswami N, Matzer F, et al (2025)

Perceived Chronic Stress prior to SARS-CoV-2 Infection Predicts Ongoing Symptomatic COVID-19: A Prospective Cohort Study.

Psychotherapy and psychosomatics pii:000547858 [Epub ahead of print].

INTRODUCTION: Understanding chronic stress as a potential risk factor for COVID-19 progression could inform public health measures and personalized preventive interventions. Therefore, we investigated the influence of chronic stress prior to SARS-CoV-2 infection on symptom persistence 1 month after COVID-19 onset.

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

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

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

RevDate: 2025-09-09

Gabernet G, Maciuch J, Gygi JP, et al (2025)

A multi-omics recovery factor predicts long COVID in the IMPACC study.

The Journal of clinical investigation pii:193698 [Epub ahead of print].

BACKGROUND: Following SARS-CoV-2 infection, ~10-35% of COVID-19 patients experience long COVID (LC), in which debilitating symptoms persist for at least three months. Elucidating biologic underpinnings of LC could identify therapeutic opportunities.

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

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

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

CLINICALTRIALS: gov NCT04378777.

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

RevDate: 2025-09-09
CmpDate: 2025-09-09

Lin JC, McCarthy M, Potluri S, et al (2025)

Long COVID and Food Insecurity in US Adults, 2022-2023.

JAMA network open, 8(9):e2530730 pii:2838652.

IMPORTANCE: Long COVID (ie, post-COVID-19 condition) is a substantial public health concern, and its association with health-related social needs, such as food insecurity, remains poorly understood. Identifying modifiable risk factors like food insecurity and interventions like food assistance programs is critical for reducing the health burden of long COVID.

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

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

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

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

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

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

RevDate: 2025-09-09

Potluri S, Chittiprol N, Varaganti V, et al (2025)

The Association of SARS-CoV-2 Infection and COVID-19 Vaccination With Sudden Death: An Explorative Review.

Cureus, 17(8):e89527.

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

RevDate: 2025-09-09

White RA, Nygaard AB, Søraas A, et al (2025)

Excess all-cause mortality in Norway in 2024.

Scandinavian journal of public health [Epub ahead of print].

AIMS: The Norwegian Institute of Public Health calculated excess mortality for Norway in 2024 using a reference period that included 2023-a year with significant excess mortality-and concluded there was no excess mortality in 2024. This study estimates excess mortality in 2024 using only pre-pandemic years as the reference, providing a basis for identifying excess COVID-19 related mortality.

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

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

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

RevDate: 2025-09-09
CmpDate: 2025-09-09

Pires L, Marreiros A, Saraiva C, et al (2025)

Association of acute COVID-19 severity and long COVID fatigue and quality of life: Prospective cohort multicenter observational study.

Medicine, 104(36):e42891.

Long COVID, or post-COVID-19 condition, is characterized by symptoms persisting beyond 12 weeks after severe acute respiratory syndrome coronavirus 2 infection, affecting individuals regardless of acute disease severity. Fatigue - often linked with depression and anxiety - is among its most debilitating manifestations. However, the associations between fatigue subtypes (physical vs mental), mental health symptoms, and acute disease severity on long-term health-related quality of life (HRQoL) remain unclear. This study examines the relationships between long COVID fatigue, depression, anxiety, acute disease severity, and HRQoL in a post-COVID-19 cohort. This prospective observational cohort study was conducted across 5 Portuguese hospitals between November 2020 and June 2022. Adults (≥18 years) with confirmed severe acute respiratory syndrome coronavirus 2 infection ≥6 months prior and fulfilling World Health Organization criteria for long COVID were included. Acute Coronavirus disease 2019 (COVID-19) severity was classified per World Health Organization definitions. The sampling strategy included patients across the severity spectrum. At 3 months postinfection (T1), patients received physician-led clinical assessments. At 6 months (T2), they attended in-person follow-up visits, completing standardized forms and validated questionnaires assessing post-acute sequelae. Fatigue was reported both binarily (yes/no) and via the chalder fatigue scale (11-item version). Anxiety and depression were assessed using the hospital anxiety and depression scale; post-traumatic stress disorder symptoms with the 14-item post-traumatic stress scale; and HRQoL with the EuroQol-5 dimensions. Descriptive statistics, analysis of variance, chi-square, and correlation analyses (Pearson's or Spearman's) were used to evaluate associations. Analyses were performed using SPSS (v27; IBM Corp., Amonk). Among 208 patients, fatigue was significantly associated with anxiety and depression (P < .001). Physical fatigue correlated more strongly with depression (r = 0.65, P < .001) and anxiety (r = 0.58, P < .001) than mental fatigue (r = 0.50 and R = 0.48, respectively; P < .001). Surprisingly, severe acute COVID-19 cases reported lower fatigue (CFQ: 13.3 ± 8.4) than mild (17.7 ± 7.2) or moderate (17.4 ± 8.0) cases (P < .005), and higher HRQoL (EuroQol visual analog scale: 74.3 ± 20.3, P = .002). Anxiety symptoms were more common in mild cases (P < .001); post-traumatic stress disorder symptoms did not differ by severity. Long COVID fatigue - especially physical - is strongly linked to depression and anxiety. Mild/moderate acute COVID-19 cases show greater fatigue and lower HRQoL than severe cases, highlighting the need for tailored long-term care regardless of initial severity.

RevDate: 2025-09-08

Claudio FD, Vallejo N, Mateu L, et al (2025)

Chest pain in long covid disease. Insights from stress cardiovascular magnetic resonance.

RevDate: 2025-09-08

Orlinick B, Mehta S, McAlpine L, et al (2025)

CSF immune cell alterations in women with neuropsychiatric Long COVID.

The Journal of infectious diseases pii:8249316 [Epub ahead of print].

BACKGROUND: Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19. However, whether there are central nervous system-specific changes in gene expression in women with neuropsychiatric Long COVID (NP-Long COVID) remains unknown.

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

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

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

RevDate: 2025-09-08

Bunnell HT, Reedy C, Lorman V, et al (2025)

A natural language processing pipeline for identifying pediatric long COVID symptoms and functional impacts in freeform clinical notes: a RECOVER study.

JAMIA open, 8(5):ooaf089.

OBJECTIVE: To develop a natural language processing (NLP) pipeline for unstructured electronic health record (EHR) data to identify symptoms and functional impacts associated with Long COVID in children.

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

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

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

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

RevDate: 2025-09-08

Sadat Larijani M, Bavand A, Ashrafian F, et al (2025)

Late-Induced Autoimmune Disorders Post-COVID-19 Vaccination/Infection: Case Report From Iran.

Case reports in medicine, 2025:8815875.

COVID-19 pandemic led to a fast vaccine design due to the threat of rapid spreading worldwide. Safety profile of the approved vaccines has been achieved mostly through clinical trials. However, some unsolicited adverse events in a longer duration of time have been recorded in addition to the late disorders known as long-COVID, stemming from classical infection. Therefore, case studies and long-term follow-up are required to enrich the current data on SARS-COV-2 infection/vaccination. In this study, two cases of autoimmune diseases induced by COVID-19 and/or vaccination were followed in three years. The profile of each is presented, and the probable cause has been discussed. The laboratory findings approved systematic lupus erythematosus and Hashimoto's thyroiditis in the studied cases. The key finding of this study is that the importance of probable autoimmune diseases flares up in individuals with a history of autoimmunity in their families which could manifest as a long-COVID symptom or late vaccination side effect.

RevDate: 2025-09-08

Gu L, Yue J, Lin J, et al (2025)

Challenges in diagnosis and treatment of long COVID.

Frontiers in medicine, 12:1641411.

Despite a large population affected by COVID-19, awareness of long COVID among clinicians is surprisingly limited. This has led to delayed or missed diagnoses and, consequently, inappropriate treatments that fail to address patients' specific needs. Our study highlights the gaps in knowledge and the barriers to effective management of long COVID in the healthcare system. Through this work, we aim to bring attention to these critical issues and advocate for urgent action to improve the clinical management of long COVID.

RevDate: 2025-09-08

Abramoff B, Dillingham T, Rybicki AK, et al (2025)

Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program to Improve the Functioning of Persons Suffering from Post-acute Sequelae of SARS-CoV-2 infection (PASC): A Randomized Controlled Trial.

Research square.

BACKGROUND: About 10-20% of persons who contract SARS CoV-2 will experience persistent post-acute sequelae of SARSCoV-2 infection (referred here as PASC). Given that persistent symptoms are heterogeneous with multisystem involvement, recent consensus recommendations suggest that a holistic rehabilitation program may be required to manage PASC and restore function. While treatments offered at emerging outpatient COVID recovery clinics are being informed by previous similar diseases, the need is great for a better understanding of the unique needs of this growing population and for tested, efficacious rehabilitation programs to address them.

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

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

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06156202.

RevDate: 2025-09-06

Houweling L, Holtjer JCS, Bloemsma LD, et al (2025)

Air pollution and long COVID: association with pulmonary function and radiological abnormalities 3-15 months post-COVID.

Environmental research pii:S0013-9351(25)01959-0 [Epub ahead of print].

While studies have examined associations between air pollution and subjective long COVID outcomes such as fatigue and symptoms, no studies have focused on objective lung health measures. This study aimed to assess the impact of air pollution, examined through different exposure methods (exposures assigned via geospatial model, versus residential and personal measurements) on pulmonary function and radiological abnormalities in long COVID patients. We recruited 95 patients who attended a hospital outpatient clinic 3-6 months post-infection, during which pulmonary function was assessed via spirometry (FEV1,FVC,FEV1/FVC ratio) and diffusion capacity for carbon monoxide (DLCO), along with a chest CT. Of these, 38 patients with abnormalities in one of the assessed modalities returned for a follow-up visit approximately nine months later. Ambient levels of PM2.5, PM10, NO2, and O3 was assigned using land-use regression models, while residential and personal PM2.5 measurements were collected between the hospital visits in the participants' home environments. No associations were found between residential (assigned or measured) air pollution exposure and pulmonary function or radiological abnormalities at the first visit. Pulmonary function also typically improved between the first and second visit. However, an association between personal exposure and CT abnormalities was observed. A one IQR(12.3 μg/m[3]) increase in personal PM2.5 significantly increased the risk of airway abnormalities during the follow-up visit (adjusted OR:3.35, 95%CI:1.03,14.63), particularly mosaic patterns (OR:5.74, 95%CI:1.43,40.62). These findings add to evidence of exposure to air pollution playing a role in long COVID and call for mitigation measures to improve air quality.

RevDate: 2025-09-06

Dixon BE, Allen KS, Simmons N, et al (2025)

Incidence of long COVID among U.S. children and adults during the omicron era - Tracking Post-COVID Conditions (Track-PCC) network, 2022-2023.

Journal of infection and public health, 18(11):102935 pii:S1876-0341(25)00284-9 [Epub ahead of print].

BACKGROUND: Long COVID, or Post-COVID Conditions (PCC), refers to new and persisting sequelae occurring in the months following an acute SARS-CoV-2 infection. Although previous studies have reported estimates of PCC incidence, few have examined trends during the Omicron variant period or have included geographically distinct regions for the same time periods.

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

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

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

RevDate: 2025-09-05

Hu C, Son J, McAlpine L, et al (2025)

Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study.

Annals of clinical and translational neurology [Epub ahead of print].

BACKGROUND: Managing long COVID in people with multiple sclerosis and related disorders (pwMSRD) is complex due to overlapping symptoms. To address evidence gaps, we evaluated long COVID susceptibility in pwMSRD versus controls and its associations with multi-domain function and disability.

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

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

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

RevDate: 2025-09-05
CmpDate: 2025-09-05

Mazzali C, Magnoni P, Zucchi A, et al (2025)

Strategies for population-level identification of post-acute sequelae of COVID-19 through health administrative data.

Frontiers in public health, 13:1637112.

INTRODUCTION: Post-acute sequelae of COVID-19 (PASC) encompass several clinical outcomes, from new-onset symptoms to both acute and chronic diagnoses, including pulmonary and extrapulmonary manifestations. Health administrative data (HAD) from health information systems allow population-level analyses of such outcomes. Our primary aim was to identify clinical conditions potentially attributable to SARS-CoV-2 infection, and the types of HAD and "diagnostic criteria" used for their detection.

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

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

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

RevDate: 2025-09-05

Salker P (2025)

My Long COVID Journey - How To Slay Dragons Using Neuroplasticity.

Journal of lifestyle medicine, 15(2):87-89.

Framed through the long COVID experience of a United Kingdom physician, this narrative delineates the neurobiological consequences of chronic stress and highlights the role of neuroplastic interventions in facilitating physiological and cognitive recovery.

RevDate: 2025-09-05

Chen Z, Li B, Chen Y, et al (2025)

Mapping Long COVID: Spatial and Social Inequities Across the United States.

medRxiv : the preprint server for health sciences pii:2025.08.21.25334183.

Background Long COVID affects a substantial portion of the U.S. population, yet its spatiotemporal distribution remains poorly characterized. The emergence of the Omicron variant and persistent sociodemographic disparities may contribute to regional variation in long COVID risk. Understanding the patterns of long COVID is essential to implementing targeted and equitable public health interventions. Methods This retrospective study utilized data from the National COVID Cohort Collaborative (N3C), covering 5,652,474 COVID-19 cases and 41,694 long COVID cases across 1,063 U.S. counties from 2021 to 2024. Temporal patterns of long COVID were analyzed before and after the Omicron variant's emergence, and spatial patterns were assessed using Moran's I and Getis statistics. Bayesian spatial random effect models were employed to evaluate the associations between long COVID incidence and sociodemographic factors such as economic vulnerability, healthcare access, and mobility. Findings Quarterly long COVID incidence ranged from 0.015% to 14.29%. Before the emergence of the Omicron variant, incidence was 204 cases per 10,000 COVID-19 cases, compared with 248 cases per 10,000 COVID-19 cases after Omicron emergence (p < 0.001). After Omicron's emergence, 48.8% [328 of 673] of counties showed significant spatial correlation (p < 0.05), up from 43.5% [293 of 673] prior. High-risk areas became more concentrated in inland regions, while low-risk areas clustered along the East Coast. Long COVID incidence was significantly associated with economic vulnerability, limited healthcare access, and mobility constraints, with these sociodemographic disparities consistently driving its spatial disparities over time. Interpretation These findings underscore the need to address spatial and social inequities in long COVID risk. Targeted public health interventions, particularly in economically and geographically vulnerable regions, are essential to ensure equitable access to diagnosis, care, and resource allocation.

RevDate: 2025-09-05

Wei WQ, Guardo C, Zhang X, et al (2025)

Multi-scale Data Improves Performance of Machine Learning Model for Long COVID Prediction.

Research square pii:rs.3.rs-7234976.

Long COVID affects a substantial proportion of the over 778 million individuals infected with SARS-CoV-2, yet predictive models remain limited in scope. While existing efforts, such as the National COVID Cohort Collaborative (N3C), have leveraged electronic health record (EHR) data for risk prediction, accumulating evidence points to additional contributions from social, behavioral, and genetic factors. Using a diverse cohort of SARS-CoV-2-infected individuals (n>17,200) from the NIH All of Us Research Program, we investigated whether integrating EHR data with survey-based and genomic information improves model performance. Our multi-scale approach outperformed EHR-only models original AUROC 0.736 (95% CI: 0.730, 0.741), achieving an AUROC of 0.748 (0.741,0.755). Among the top predictors, active-duty service status, self-reported fatigue, and chr19:4719431:G:A_A were among the most informative survey and genetic features. These findings highlight the importance of incorporating multi-scale data to improve risk stratification and inform personalized interventions for long COVID.

RevDate: 2025-09-05

Leighton J, Nelson MLA, Sheppard CL, et al (2025)

'You're alive, but are you living?' Exploring long COVID (LC)'s impact on social and leisure well-being for individuals and caregivers.

Psychology & health [Epub ahead of print].

Long COVID (LC) affects physical health and cognition, limiting participation in social and leisure activities. As a novel disabling condition following a COVID-19 infection, informal caregivers of those with LC have taken on expanded roles, including educating themselves on this diagnosis. Gathering insights from people living with LC (PWLC) and their caregivers is crucial for understanding its impact on well-being and identifying targeted rehabilitation practices across the LC care pathway. Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with LC and 15 caregivers). Results: Composite narratives were created to introduce three key themes: (1) The demands of managing physical and cognitive symptoms of LC limit the ability of PWLC and caregivers to engage in social and leisure activities; (2) The loss of meaningful social and leisure activities deepens a diminished sense of identity for PWLC and caregivers; and (3) The absence of shared social and leisure engagement intensifies feelings of disconnection and loneliness for PWLC and caregivers. The findings support a need for more social- and leisure-targeted interventions for LC rehabilitation to help to optimize efforts for coping with the psychosocial impacts of living with, or caring for someone with, LC.

RevDate: 2025-09-04

Ivković V, Anandh U, Bell S, et al (2025)

Long COVID and the kidney.

Nature reviews. Nephrology [Epub ahead of print].

Long coronavirus disease (COVID) - commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis - is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.

RevDate: 2025-09-04

Colombo C, Medino P, Cipolli M, et al (2025)

COVID-19 in people with Cystic Fibrosis beyond the pre-omicron era: a prospective study with a specific focus on long COVID.

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society pii:S1569-1993(25)01574-7 [Epub ahead of print].

BACKGROUND: The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF.

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

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

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

RevDate: 2025-09-04

Tashima R, Kuroda T, Nobori H, et al (2025)

Ensitrelvir suppresses prolonged olfactory abnormalities derived from SARS-CoV-2 infection in hamsters.

Antiviral research pii:S0166-3542(25)00196-2 [Epub ahead of print].

Ensitrelvir, an oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease inhibitor, is reportedly effective in suppressing smell disorder onset, a post-coronavirus disease 2019 (COVID-19) condition symptom. However, the pathogenesis of post-COVID-19 condition symptoms and the mechanism underlying the onset-suppressive effect of ensitrelvir are not fully understood. Here, we explored a post-COVID-19 condition model in hamsters 1 month post-SARS-CoV-2 infection and showed that ensitrelvir treatment caused early recovery of body weight, viral RNA suppression, and sense of smell improvement. In the nasal turbinates, SARS-CoV-2 was associated with significantly increased inflammatory markers, many of which were suppressed by ensitrelvir. Significant positive correlations were observed between smell testing and many inflammation-related markers in the nasal turbinates. In conclusion, our study indicates that chronic inflammation may occur in the nasal turbinates over a long period post-SARS-CoV-2 infection, leading to smell disorder onset in a hamster model. Early ensitrelvir treatment post-infection suppressed inflammation in the nasal turbinates and prevented smell disorder onset.

RevDate: 2025-09-04

Tobey M, Purvis SJ, Daubman BR, et al (2025)

The Experience of Long COVID Among American Indian Individuals in Three Great Plains Communities.

Journal of racial and ethnic health disparities [Epub ahead of print].

Long COVID may impact populations differently. In July 2023, at the direction of a community advisory board, we administered a cross-sectional survey to explore attitudes and experiences of long COVID among members of three American Indian Reservation communities in the Great Plains. Just over half of the 843 respondents considered long COVID to be an important issue in their community, an attitude that was associated with younger age, identifying as male, having more than a high school education, full-time employment, living with children, and living on the Reservation. Of survey respondents who reported having had COVID-19, 40% reported ongoing symptoms at the time of the survey. Having ongoing symptoms was associated with identifying as female, living alone with children, and having had long COVID-19 symptoms during the initial infection. To explore ongoing symptoms, we performed a factor analysis that identified three symptom clusters with distinct sociodemographic associations. The results suggest that health and workforce sequelae of COVID-19 infections may present challenges for the surveyed communities and that ongoing symptoms after COVID-19 infection were common.

RevDate: 2025-09-04

Gracie NP, Aggarwal A, Luo R, et al (2025)

An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.

Journal of virology [Epub ahead of print].

UNLABELLED: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates canonical cell entry via ACE2 and has also been implicated as an activator of a diverse range of signaling pathways. Here, we present evidence that the RGD (Arg-Gly-Asp) motif within the receptor-binding domain (RBD) of the S1 fragment of the S protein induces TGF-β cytokine expression. RGD peptides are well characterized as ligands for a subset of integrin complexes primarily containing α5 and αV subunits. In this study, we investigate the molecular basis of TGF-β pathway activation by S protein, delivered to cells as recombinant protein, in pseudotyped virus or in virally infected cells. Activation of TGF-β signaling by the S protein requires ACE2 and leads to SMAD3-dependent expression of the pro-fibrotic marker PAI-1. Utilizing pseudotyped viruses, expression of the S protein with a mutated RGD motif abolished TGF-β signaling, as did the RGD antagonist ATN-161, implicating integrin complexes in mediating this response. We show that the S protein RGD motif suppresses IFN-β expression via TGF-β, leading to a disruption in cellular antiviral defenses, consistent with TGF-β's role in immunosuppression. These findings further support the multifunctionality of S protein and provide mechanistic insights into its activity as a virulence factor during infection.

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

RevDate: 2025-09-04
CmpDate: 2025-09-04

Lotankar Y, Cheshire A, Ridge D, et al (2025)

Intersectionality and Long Covid: Understanding the Lived Experiences of Ethnic Minority Groups in the United Kingdom.

Health expectations : an international journal of public participation in health care and health policy, 28(5):e70413.

INTRODUCTION: Long Covid is the patient-preferred term to describe persistent symptoms experienced following an acute Covid-19 infection. The severity and unpredictable nature of long Covid symptoms can affect every aspect of an individual's life. Under-represented groups such as ethnic minorities and lower socio-economic groups are disproportionately affected by long Covid and often face challenges in accessing healthcare and additional support. This study employed an intracategorical intersectionality approach to explore how the diverse experiences of long Covid among people from ethnic minority backgrounds are influenced by complexities like gender and socio-economic factors.

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

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

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

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

RevDate: 2025-09-04

Shen S, Zhao X, Pei J, et al (2025)

Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.

Frontiers in psychiatry, 16:1555370.

Long COVID (LC) refers to a multisystem condition that persists after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). In addition to physical symptoms, the psychological impact is particularly pronounced. This review summarizes the manifestations, potential mechanisms, epidemiological characteristics, and current interventions related to psychological disorders in LC. Drawing on domestic and international literature, it highlights anxiety, depression, cognitive dysfunction, and post-traumatic stress disorder (PTSD) as the primary psychological symptoms. These symptoms may be associated with neuroinflammation, immune abnormalities, vascular dysfunction, and psychosocial stress. Although research in this area is still developing, psychotherapy, pharmacotherapy, neuromodulation, and lifestyle interventions show promise as treatment approaches. This review aims to provide insights that can inform future research on clinical treatments and psychological care for individuals with LC.

RevDate: 2025-09-03

Nguyen NN, Tissot-Dupont H, Brouqui P, et al (2025)

Post-COVID syndrome in symptomatic COVID-19 patients: a retrospective cohort study.

BMC infectious diseases, 25(1):1099.

BACKGROUND: Although post-COVID symptoms have been documented in the literature, the risk factors and time required for full recovery remain unclear. We conducted a retrospective analysis of medical records of COVID-19 patients to investigate the prevalence of symptoms after an acute episode of COVID-19 and the risk factors for persistence of symptoms.

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

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

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

RevDate: 2025-09-03

Colgan DD, Stadler DD, Hope AA, et al (2025)

Clinically Meaningful Improvements in Long COVID Symptoms Following Ketogenic Metabolic Therapy Combined with Lifestyle Interventions-A Clinical Case Report and Review of the Literature.

Case reports in clinical medicine, 14(8):391-410.

Approximately 400 million individuals globally are estimated to suffer from Long COVID, an infection-associated chronic condition that occurs after SARS-CoV-2 infection. Despite the high burden, there are no evidence-based or FDA-approved interventions to treat the condition. Given its complexity, a multicomponent approach grounded in a whole-person health model is likely required. This case report highlights clinically meaningful improvements in multiple Long COVID symptoms following a remotely-delivered, ketogenic metabolic therapy combined with group health coaching. Nutritional interventions were paired with exercises to stabilize circadian rhythms and introduce mindfulness-based practices. A review of the literature provides evidence in support of ketogenic metabolic therapy and lifestyle interventions as strategies to target proposed underlying mechanisms of Long COVID and foster stress resilience, thus reducing symptoms and improving quality of life. Findings support future research to optimize and evaluate multimodal nutritional and lifestyle interventions for Long COVID.

RevDate: 2025-09-03
CmpDate: 2025-09-03

Pokharel BR, Majumdar N, Williams F, et al (2025)

SARS-CoV-2 infection of substantia nigra pars compacta induces expression of miR-330-5p at 10 days post-infection.

The Journal of general virology, 106(9):.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been linked to several neurological symptoms in coronavirus disease 2019 (COVID-19) patients; however, the molecular mechanisms underlying virus-induced neuroinflammation are not well identified. For example, the effect of SARS-CoV-2 infection of the substantia nigra pars compacta (SNpc) of the midbrain has not been addressed, in spite of its importance in dopaminergic signalling and neurodegenerative abnormalities. The purpose of this study was to understand the SARS-CoV-2-induced inflammatory response in the SNpc region of the brain. We inoculated (intranasally) transgenic mice expressing human ACE2 under control of the human keratin 18 promoter (K18-hACE-2 mice) with a 4×10[3] TCID50 (mild) dose of SARS-CoV-2. Ten days post-inoculation, SARS-CoV-2 was detected in the SNpc of mice, along with increased levels of IL-1β, B1R and ADAM17, and reduced microglial/macrophage occurrence. miR-330-5p expression was significantly reduced in virus-positive SNpc tissue. Luciferase reporter assays supported ADAM17 as a direct target of miR-330-5p. There was no significant difference in miR-330-5p expression levels in the experimental autoimmune encephalomyelitis mice compared to control mice, demonstrating a crucial role for SARS-CoV-2-induced miR-330-5p in brain pathology. Our study uncovers for the first time that SARS-CoV-2 can invade the SNpc and downregulate miR-330-5p expression levels, causing an enhanced ADAM17 expression and possible neuroinflammatory signalling. The results implicate miR-330-5p as a prospective therapeutic target for alleviating midbrain inflammation associated with SARS-CoV-2 infection.

RevDate: 2025-09-03

Ahmad A, Janjua NZ, Lix LM, et al (2025)

A national atlas to improve the study of Canadians living with long COVID (post-COVID-19 condition).

Canadian journal of public health = Revue canadienne de sante publique [Epub ahead of print].

OBJECTIVES: To develop a national atlas of (1) Canadian cohorts studying or with the potential to study adults living with long COVID (LC) and (2) harmonize provincial and territorial administrative datasets to facilitate the creation of validated case-ascertainment algorithms and foster national collaboration on LC research.

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

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

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

RevDate: 2025-09-03
CmpDate: 2025-09-03

Bai W, F Li (2025)

Regulation of m7G methylation in long COVID: Expression profiles and early predictive value of key genes.

Medicine, 104(35):e44209.

Long COVID (LC) poses ongoing public health challenges due to its persistent symptoms following severe acute respiratory syndrome coronavirus 2 infection. Early identification of at-risk individuals remains difficult, and molecular biomarkers are urgently needed. This study aimed to explore the role of N7-methylguanosine (m7G) methylation-related regulatory genes in LC pathogenesis and to develop a predictive model for early detection. Gene expression profiles of LC patients were obtained from the GEO database (GSE224615), and differentially expressed genes (DEGs) were identified. These DEGs were intersected with m7G regulatory genes to identify LC-specific candidates. A protein-protein interaction network was constructed to identify hub genes, and enrichment analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were performed to investigate the biological relevance of the identified genes. Immune cell infiltration analyses were conducted to explore the immunological features associated with candidate genes. Findings were validated using an external dataset (GSE217948). A clinical prediction model was constructed using Least absolute shrinkage and selection operator regression followed by logistic regression, and evaluated via receiver operating characteristic curve, calibration, and decision curve analysis. A total of 65 DEGs were identified in LC patients, comprising 44 up-regulated and 21 down-regulated genes. Thirty genes overlapped with the m7G regulatory gene set. Functional enrichment revealed significant involvement in pathways such as FceRI-mediated NF-κB activation and platelet aggregation. Correlation analysis showed that several m7G-related genes were associated with altered immune cell infiltration patterns. The external dataset confirmed the reproducibility of gene expression trends. Seven core genes were ultimately selected to build the predictive model, which demonstrated robust performance in distinguishing LC patients from controls. This study highlights the importance of m7G methylation in LC pathogenesis and uncovers novel immune-related mechanisms underlying its persistence. The predictive model based on m7G-related markers provides a promising tool for early LC identification and may inform future diagnostic and therapeutic strategies.

RevDate: 2025-09-02

McDuff K, Bhéreur A, Kadakia Z, et al (2025)

Establishing a framework of measurement for use in Long COVID research and practice: protocol for a scoping review involving evidence review and consultation.

BMJ open, 15(9):e094497 pii:bmjopen-2024-094497.

INTRODUCTION: Our aim is to develop a Framework of Measurement for people living with Long COVID and their caregivers for use in Long COVID research and clinical practice. Specifically, we will characterise evidence pertaining to outcome measurement and identify implementation considerations for use of outcome measures among adults and children living with Long COVID and their caregivers.

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

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

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

RevDate: 2025-09-02

Eltoum AI, Begum R, Gold LS, et al (2025)

Exploring the Associations between Self-Reported Sleep Disturbance and Cognitive Impairment among Survivors of COVID-19 Hospitalization.

Mental health science, 3(3):.

STUDY OBJECTIVES: Cognitive impairment following COVID-19 infection is common and risk factors remain poorly understood. Sleep disturbance increases risk of cognitive impairment in the general population, and sleep disturbance is common after COVID-19. While prior literature has extensively explored the relationship between sleep and cognition, few studies have addressed the temporality of this association and how one may contribute to the other over time. This study assessed whether new sleep disturbance at 1-month is associated with risk of cognitive impairment at 6-months after COVID-19 hospitalization.

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

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

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

RevDate: 2025-09-02

Kwissa M, Mathayan M, Salunkhe SS, et al (2025)

Persistent Immune Dysregulation during Post-Acute Sequelae of COVID-19 is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.

bioRxiv : the preprint server for biology pii:2025.08.18.670908.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome or "Long COVID" represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of PASC, but the extent of PASC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed PASC. Compared to convalescent, PASC participants with a broad range of PASC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the PASC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis, we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa-associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in PASC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in PASC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity.

RevDate: 2025-09-02

Dias Rodrigues G, Fazan R, N Montano (2025)

Editorial: Updates on cardiovascular variability: underlying mechanisms and non-pharmacological therapeutic targets.

Frontiers in cardiovascular medicine, 12:1670996.

RevDate: 2025-09-02

Zeng J, X Jia (2025)

Quantifying compatibility mechanisms in traditional Chinese medicine with interpretable graph neural networks.

Journal of pharmaceutical analysis, 15(8):101342.

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

RevDate: 2025-09-02
CmpDate: 2025-09-02

Jothi S, Insel M, Claessen G, et al (2025)

Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.

Physiological reports, 13(17):e70535.

Post-acute sequelae of SARS-CoV-2 (PASC or "long COVID") and chronic fatigue syndrome/myalgic encephalitis (CFS/ME) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 PASC patients, 11 CFS/ME patients, and 11 controls. We evaluated the contributions of alveolar ventilation (V̇a), lung diffusion capacity (DL), cardiac output (Q̇), skeletal muscle diffusion capacity (DM), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (Vmax) to peak oxygen consumption (V̇O2peak). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V̇O2peak. V̇O2peak was significantly reduced in both PASC and CFS/ME compared to controls. Skeletal muscle O2 diffusion (DM) was the most impaired parameter in both patient groups (p = 0.01). Correcting DM alone improved V̇O2 by 66% in PASC (p = 0.008) and 34.7% in CFS/ME (p = 0.06), suggesting a dominant role for peripheral O2 extraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (DM) is a shared mechanism of exercise intolerance in PASC and CFS/ME and may represent a therapeutic target. However, our findings are limited by small sample size.

RevDate: 2025-09-01
CmpDate: 2025-09-01

Gomez-Bravo R, León-Herrera S, Guisado-Clavero M, et al (2025)

Towards consensus: The need for standardised definitions in Long (post) COVID care in 34 European countries.

The European journal of general practice, 31(1):2535618.

BACKGROUND: The COVID-19 pandemic has significantly impacted global healthcare systems, leading to challenges in managing Long COVID. Variations in definitions and diagnostic criteria across Europe hinder recognition and treatment efforts. This study aims to analyse and compare the definitions of Long COVID used in 34 European countries.

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

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

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

RevDate: 2025-09-01

Fain MJ, Horne BD, Horwitz LI, et al (2025)

Age-Related Changes in the Clinical Picture of Long COVID.

Journal of the American Geriatrics Society [Epub ahead of print].

BACKGROUND: This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID.

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

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

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

RevDate: 2025-09-01
CmpDate: 2025-09-01

Parums DV (2025)

Editorial: Dormant Cancer Cells, Cancer Progression, and Post-Acute Sequelae of COVID-19 and Influenza.

Medical science monitor : international medical journal of experimental and clinical research, 31:e951178 pii:951178.

Since the COVID-19 pandemic, vaccine uptake has fallen, and awareness of the long-term consequences of respiratory virus infections, particularly long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has also lost momentum. After a decade of declining mortality rates from cancer in the US, from 2020, registered age-standardized cancer-related deaths and mortality increased for all cancers. Cancer cell 'dormancy' results from an equilibrium between tumor cell division and apoptosis, and provides an explanation for relapse and metastasis that can occur months, years, or decades after treatment. In July 2025, findings from a study in mice infected with influenza and SARS-CoV-2 showed the rapid loss of the pro-dormancy phenotype in breast carcinoma cells in the lung, and expansion of metastatic carcinoma cells within weeks. Animal model findings support findings in cancer survivors that SARS-CoV-2 infection was significantly associated with an increased risk of lung metastasis and cancer-related mortality. This Editorial aims to highlight findings from real-world population studies on the association between COVID-19 and cancer and new experimental findings for how SARS-CoV-2, influenza, and possibly other respiratory viruses may 'awaken' dormant cancer cells.

RevDate: 2025-09-01

Chaichana U, Man KKC, Ju C, et al (2025)

Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:8244943 [Epub ahead of print].

BACKGROUND: A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post-COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.

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

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

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

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

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

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

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

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

RevDate: 2025-08-31

Klein DO, Wilmes N, Waardenburg SF, et al (2025)

Development and internal validation of a prediction model for post-COVID-19 condition 2 years after infection-results of the CORFU study.

Diagnostic and prognostic research, 9(1):18.

BACKGROUND: A subset of COVID-19 patients develops post-COVID-19 condition (PCC). This condition results in disability in numerous areas of patients' lives and a reduced health-related quality of life, with societal impact including work absences and increased healthcare utilization. There is a scarcity of models predicting PCC, especially those considering the severity of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and incorporating long-term follow-up data. Therefore, we developed and internally validated a prediction model for PCC 2 years after SARS-CoV-2 infection in a cohort of COVID-19 patients.

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

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

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

RevDate: 2025-08-31

do Nascimento KF, Alchieri EF, Sanson CS, et al (2025)

Neuroinflammation in long COVID: the role of the Val16Ala polymorphism of SOD2 and cognitive impairment.

Neuroscience pii:S0306-4522(25)00895-4 [Epub ahead of print].

Long COVID (LC) includes persistent behavioral and cognitive deficits, impacting quality of life. Neuroinflammation plays a key role in these alterations, with genetic factors influencing susceptibility. The MnSOD Val16Ala SNP is associated with neuroinflammation and cognitive dysfunction, but its role in LC remains unclear. This study investigated the relationship between the SOD2 Val16Ala polymorphism and neurocognitive alterations in young adults post-SARS-CoV-2 infection. Neurocognitive performance was assessed using the Neupsilin test in individuals with and without prior COVID-19. Blood samples were collected for the quantification of cytokines (IL-1, IL-6, TNF-α, and IFN-γ) and for the genotyping of the SOD2 Val16Ala polymorphism. The COVID-19 group showed worse cognitive performance and higher cytokine levels than controls, particularly in memory and executive function. Val allele carriers (Val/Ala and Val/Val) exhibited increased pro-inflammatory cytokine levels compared to Ala/Ala carriers. These findings suggest a potential interaction between genetic susceptibility and inflammatory response in post-COVID neurocognitive alterations. Young adults post-COVID-19 presented an exacerbated neuroinflammatory response, likely influencing cognition. The presence of the Val allele was associated with greater susceptibility to inflammatory events, suggesting a genetic component in LC-related neurological dysfunction. These results reinforce the role of neuroinflammation in LC and highlight the importance of genetic factors in determining cognitive outcomes. Understanding these mechanisms may help identify individuals at higher risk and support future therapeutic strategies.

RevDate: 2025-08-30

Fernández-de-Las-Peñas C, Ruiz-Ruigómez M, Esparcia-Pinedo L, et al (2025)

Classical Pathway Persistent Complement Activation is Associated with Specific Symptoms in Individuals with Post-COVID-19 Condition: A Case-Control Study.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases pii:S1201-9712(25)00254-1 [Epub ahead of print].

OBJECTIVE: The complement system is a crucial part of the immune system. The role of complement activation in post-COVID-19 condition is still not conclusive. We present a case-control study investigating long-lasting complement hyperactivation in COVID-19 survivors with/without post-COVID-19 condition.

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

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

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

RevDate: 2025-08-30

Edwards DL, Feldstein LR, Dalton AF, et al (2025)

Prevalence of symptoms associated with Long COVID among adolescents in the United States, Summer 2022.

The Journal of infectious diseases pii:8244680 [Epub ahead of print].

PURPOSE: Limited information is known about Long COVID among adolescents. This study will compare the risks associated with symptoms among adolescents who tested positive, were tested but never tested positive, and who were never tested for SARS-CoV-2 infection.

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

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

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

RevDate: 2025-08-30
CmpDate: 2025-08-30

Mak WA, Wapperom D, Redel AL, et al (2025)

Seasonal Coronavirus-Induced Immunological Imprinting and Previous Herpesvirus Infections in Patients With Long COVID.

Journal of medical virology, 97(9):e70582.

Long COVID (LC) is a post-acute infection syndrome affecting 5%-10% of individuals infected by SARS-CoV-2. Here, we aimed to study SARS-CoV-2 humoral immunity, immunological imprinting by endemic coronaviruses, and previous herpesvirus infections in LC. We included 47 LC patients and 41 controls who fully recovered from COVID-19. We assessed IgG, IgA, and IgM antibody levels against SARS-CoV-2, seasonal coronaviruses, and herpesviruses using ELISAs and Microblot-Array panels. Additionally, we performed PCR to detect viral RNA/DNA and evaluated anti-nuclear autoantibodies linked to systemic autoimmune conditions. LC patients showed significantly reduced levels of SARS-CoV-2 anti-spike IgG and IgA but increased levels of endemic coronaviruses OC43 and HKU1 anti-spike IgG, suggesting immunological imprinting potentially driven by these coronaviruses. Furthermore, LC patients had higher levels of SARS-CoV-2 anti-spike IgM compared to anti-Spike IgG, possibly indicating impaired class switching. Interestingly, cytomegalovirus (CMV) p65 IgG levels were lower in LC patients and negatively correlated with fatigue severity. This study highlights immunological imprinting by seasonal coronaviruses and impaired antibody class switching as potential causes of SARS-CoV-2 immune escape and persistence in LC patients. Furthermore, our findings suggest an inverse association between CMV p65 IgG and fatigue severity in LC.

RevDate: 2025-08-29

Kamal SM, Al Qahtani MS, Al Aseeri A, et al (2025)

Long COVID-19: a Four-Year prospective cohort study of risk factors, recovery, and quality of life.

BMC infectious diseases, 25(1):1082.

RevDate: 2025-08-29

Fayyad-Kazan M (2025)

MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential.

Inflammopharmacology [Epub ahead of print].

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

RevDate: 2025-08-29

Mizuno A (2025)

Stirring the POTS: Finding Symptom Patterns in Long COVID.

JACC. Advances, 4(8):101869.

RevDate: 2025-08-29

Al Mouslmani M, Sawano M, Arun AS, et al (2025)

Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study.

JACC. Advances, 4(8):101873.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID.

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

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

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

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

RevDate: 2025-08-29
CmpDate: 2025-08-29

Ferreira AMS, Ferreira FELL, Alverga CCF, et al (2025)

Symptoms and Risk Factors for Long COVID: A Cross-Sectional Study in Primary Care.

Journal of medical virology, 97(9):e70579.

This study aimed to determine the occurrence and risk factors for persistent symptoms after mild to moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients who presented in primary care during the 2021 pandemic. A retrospective cross-sectional survey was conducted in six public family health care units in Joao Pessoa, Brazil. A questionnaire with a set of 18 validated clinical outcomes was used to assess prolonged symptoms beyond 3 months of duration in 226 adults who had confirmed SARS-CoV-2 infection. Binary logistic regression models were used to estimate adjusted odds ratios (aOR) and risk factors for Long COVID. A total of 16 outcomes were significantly associated with Long COVID. The largest aOR were estimated for short-term memory loss, anxiety, and loss of attention. The risk factors for Long COVID included ≥ 5 symptoms (15.82, 7.33-34.15, p < 0.0001), female sex (aOR: 1.91, 95% CI: 1.03-3.53, p = 0.032), age 40-49 years (3.45, 1.14-10.51, p = 0.029), and age 70+ years (4.0, 1.01-15.51, p = 0.045). Findings highlight a high frequency of persistent symptoms in adults who initially had non-severe SARS-CoV-2 infection, who are predominantly of working age, and who did not present multiple comorbidities. This study supports the need for assessing clinical outcomes and risk factors on Long COVID in primary care using routinely recorded clinical outcomes.

RevDate: 2025-08-29

Herlitz J, Pohl A, AL Gerlach (2025)

Googling as avoidance: anxiety responses to online health information about long COVID.

Anxiety, stress, and coping [Epub ahead of print].

Background and Objectives: People search the internet for health information, although this increases anxiety and worry, particularly in the health-anxious. Applying the avoidance theory of worrying, we tested whether online health research serves to emotionally distance oneself from illness.Design and Method: Googling long COVID was compared to imagery of suffering from the disease in 60 participants. We assumed that anxiety responses to googling would be lower than during imagery, but higher than during baseline. Self-report, skin conductance (SCL), heart rate (HR), heart rate variability (HRV), and respiration rate (RR) indicated anxiety.Results: SCL was higher during imagery than googling. However, HR, high frequency HRV and RR signaled stronger activation by googling than imagery. Physiological measures demonstrated a stronger anxiety response to googling compared to baseline. Regarding self-report, an interaction effect of sequence and condition emerged. Those who started with googling reported higher levels of anxiety during imagery. Among participants who began with imagery, anxiety was elevated during googling compared to baseline, but there were no significant differences when compared to anxiety during imagery.Conclusions: Results at least partially support the notion that health-related internet research may serve to avoid the physical and self-reported anxiety responses.

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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.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

long standard version

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