Sequelae Of COVID-19 Research Articles

Cdc42 improve SARS-CoV-2 spike protein-induced cellular senescence through activating of Wnt/β-Catenin signaling pathway

IntroductionSARS-CoV-2 infection drove senescent cells and the senescence-associated phenotypes were reported playing roles in disease progression, which contributes to severe COVID-19 and related sequelae. Cdc42 is involved in the regulation of cellular senescence. This study, aimed to investigate the mechanism of the SARS-CoV-2 spike protein regulating cellular senescence through Cdc42.MethodsK18-hACE2 mice were infected with SARS-CoV-2 Omicron BA.4 or stimulated with spike protein through the airway, the senescent cells and Cdc42 expression in lung tissue were detected. Overexpression of spike protein or exogenous incubation of spike protein was used to simulate the induction of cellular senescence by spike protein. Mechanistic insights into the role of Cdc42 were mainly explored using Western Blot and qRT-PCR.ResultsSpike protein, SARS-CoV-2 infection related, accelerates cell aging by upregulating Cdc42 expression, which furtherly activated the Wnt/β-catenin signaling pathway. Conversely, treatment with ML141 in animal models, a Cdc42 inhibitor, reduced cellular senescence and ameliorated lung injury and inflammation. These results suggest that the upregulation of Cdc42 by the SARS-CoV-2 spike protein induces cellular senescence and enhances β-catenin nuclear translocation.DiscussionThis study provides insights into the mechanisms underlying cellular senescence induced by the SARS-CoV-2 spike protein, offering potential strategies to mitigate the inflammatory response and complications associated with COVID-19 in both the acute and long-term phases.

Beyond acute infection: mechanisms underlying post-acute sequelae of COVID-19 (PASC).

Immune dysregulation is a key aspect of post-acute sequelae of coronavirus disease 2019 (PASC), also known as long COVID, with sustained activation of immune cells, T cell exhaustion, skewed B cell profiles, and disrupted immune communication thereby resulting in autoimmune-related complications. The gut is emerging as a critical link between microbiota, metabolism and overall dysfunction, potentially sharing similarities with other chronic fatigue conditions and PASC. Immunothrombosis and neurological signalling dysfunction emphasise the complex interplay between the immune system, blood clotting, and the central nervous system in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clear research gaps in the design of PASC studies, especially in the context of longitudinal research, stand out as significant areas of concern.

Socio-demographic and clinical predictors of post-acute, mid-and long-term psychological sequelae of COVID-19: a two-year cross-sectional investigation on 1317 patients at the University Hospital of Verona

BackgroundThe present paper focuses on socio-demographics, clinical variables, and the distance from the infection in predicting the long-term psycho-social consequences of COVID-19.MethodsPatients were screened with a cross-sectional design at the Psychological Service of the University Hospital of Verona (Italy) at 3, 6, 12, and 18 months after their SARS-CoV-2 infection. The assessment was part of the Horizon 2020-funded ORCHESTRA Project and included the Hospital Anxiety and Depression Scale (HADS), the Short Form Health Survey 36 (SF-36), the Impact of Event Scale-Revised (IES-R), and ad-hoc questions measuring pre-post COVID-19 changes on psycho-social dimensions (sleep quality, nutrition, level of autonomy, work, social relationships, emotional wellbeing).ResultsBetween June 2021 and June 2023, we evaluated 1317 patients (mean age 56.6 ± 14.8 years; 48% male): 35% at three months, 40% at 6, 20% at 12, and 5% at 18 months after the infection. Thirty-five percent were hospitalized due to COVID-19. Overall, 16% reported some form of clinically significant mental distress following the infection (HADS-TOT), with 13% and 6%, respectively, experiencing anxiety (HADS-Anxiety) and depressive symptoms (HADS-Depression). Four percent testified post-traumatic symptoms. The SF-36 scale revealed that 16% and 17% of subjects had physical or psychological deterioration in quality of life, respectively. The regression analyses showed that females experienced higher levels of anxiety and depression compared to males, along with worse mental and physical quality of life and pre-post infection changes in nearly all the investigated psycho-social dimensions. Younger people felt more anxiety and had a reduced mental quality of life than their older counterparts, who, in turn, had poorer scores in terms of autonomy and physical functioning. Hospitalized patients had lower levels of self-sufficiency, social relationships, and work than non-hospitalized people. The latter were more anxious and reported a lower physical quality of life. Finally, patients evaluated for the first time at 12- and 18 months showed a more significant impairment in mental and physical quality of life than those assessed at three months.ConclusionsOur data show that COVID-19 psychological sequelae tend to persist over time, still needing clinical attention and intervention planning, especially for females.

Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function.

An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups-recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals-revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation's role in the symptoms of PASC-CVS.

Substantial morbidity and mortality due to cardiovascular diseases in hospitalized vaccinated and un-vaccinated patients with COVID-19 from 16 countries: the WHF COVID-19 Long-term study

Abstract Background Long-term adverse consequences of the COVID-19 affect many organ systems, and this requires the identification and appropriate care of diverse symptoms. Purpose The World Heart Federation (WHF) international study describes the burden of clinical sequelae of COVID-19 up to 1 year after hospitalization, including patients from low- middle-and high-income countries. Methods We prospectively recruited patients hospitalized due to COVID-19 from 16 countries between January 2022 and June 2023. Patients were followed up at 1, 3, 6, and 9-12 months after hospital discharge. A standardized questionnaire administered by telephone collected data on long COVID symptoms, quality of life using the EuroQol 5 Dimension scale (EQ-5D), and disease outcomes including new onset diabetes and hypertension, major adverse cardiovascular events (MACE), and mortality. We report a descriptive analysis including demographic characteristics and outcomes up to one year after initial hospitalization. Results Of 2504 patients, the majority were Asian (78%), and male (56%). Mean age was 59.2 years (SD 19.9). Low- and lower-middle-income country participants constituted 65% of the cohort, with upper middle-income and high-income representing 20% and 15%, respectively. Follow-up rate was complete for 86%. 55% had received at least two doses of COVID-19 vaccination. At 1 month, 63% reported at least one persistent symptom, which decreased to 28% at 9-12 months. Fatigue was reported by 45% at 1-month and 17% at final follow-up. Anxiety occurred in 20% and 9% at these respective timepoints, and breathlessness in 12% and 6%. At 9-12 months, moderate to severe impairment of usual activities as measured by EQ-5D occurred in 19%, anxiety/depression in 10%, and mobility problems in 10%. The most frequent post-discharge new-onset illnesses were pulmonary embolism (7%), kidney problems (4%), and hypertension (3%). In-hospital mortality was 4% (n=102), and a further 12% (265 patients) died by one-year. The most common cause was sudden cardiac death (59%), respiratory disease including pulmonary embolism (13%), and stroke (6%). Conclusions We observed a significant burden of post-COVID-19 complications with one fifth of patients with persistent difficulties in usual activities at one year. This underscores the urgent need to understand the underlying mechanisms for organ damage and death, and for targeted preventive strategies and proactive management approaches to reduce them.

Aberrations in medically certified sick leave and primary healthcare consultations in Norway in 2023 compared to pre-COVID-19-pandemic trends

BackgroundSince 2022, Norway has employed a vaccine-only COVID-19 strategy. Primary healthcare in Norway uses International Classification of Primary Care version 2 (ICPC-2) codes. This study aims to systematically compare medically certified sick leave and primary healthcare consultations in 2023 with the pre-pandemic 2010–2019 trends, and subsequently estimate the magnitude of these changes.MethodsFor the respective outcomes of (A) working person-years lost to medically certified sick leave (WYLSL) and (B) number of primary healthcare consultations, 556 and 85 ICPC-2 code combinations were extracted from the Norwegian Labour and Welfare Administration’s sick leave registry and the Norwegian Syndromic Surveillance System. For each ICPC-2 code combination, a Bayesian linear regression was performed using data between 2010 and 2019 to estimate an expected baseline for 2023, which was then used to calculate the deviation from the pre-pandemic trend. A false discovery rate of 5% was used to account for multiple testing.ResultsAll years from 2020 to 2023 had excess WYLSL, corresponding to 14,491 (90% PI: 8,935 to 20,016) in 2020, 12,911 (90% PI: 5,916 to 19,996) in 2021, 21,263 (90% PI: 12,627 to 29,864) in 2022, and 24,466 (90% PI: 14,023 to 34,705) in 2023. This corresponded to an economic loss of approximately 1.5 billion USD in 2023. Excess WYLSL due to A* (General and unspecified) increased from 2020 to 2023, with an estimated excess of 4,136 WYLSL in 2023 (69% higher than expected). More than half of this increase was explained by A04 (Weakness/tiredness general), whose excess WYLSL in 2023 were estimated at 2,640 (80% higher than expected). The excess in A04 (Weakness/tiredness general) corresponded to an economic loss of 161 million USD and accounted for 11% of the total excess WYLSL in 2023. The excess WYLSL in R* (Respiratory) in 2023 was 3,408, which correspond to an economic loss of 207 million USD and accounted for 14% of the total excess in 2023.ConclusionsSignificant excesses in working person-years lost to medically certified sick leave and primary healthcare consultations in 2023. A sizable proportion of the excesses were due to diseases/symptoms associated with acute and post-acute sequelae of COVID-19.

Musculoskeletal, Pulmonary, and Cardiovascular COVID-19 Sequelae in the Context of Firefighter Occupational Health: A Narrative Review.

For most individuals infected with SARS-CoV-2, the acute illness resolves completely. However, for millions of people, symptoms or sequelae from COVID-19 recur or persist for months to years after infection. Post-COVID-19 sequelae are wide-ranging, often affecting the musculoskeletal, pulmonary, and cardiovascular systems. All who experience post-COVID-19 sequelae face significant challenges navigating home and work life. Occupations such as firefighting, however, are of particular concern given the strenuous nature of a job that relies on a healthy musculoskeletal, pulmonary, and cardiovascular system. Research has documented significant musculoskeletal impairment (including muscle weakness, pain, and fatigue), respiratory dysfunction (including reduced lung function, interstitial disease, and diffusion abnormalities), cardiovascular conditions (including cardiac events, ischemic disease, dysrhythmias, and infectious diseases), and diminished cardiorespiratory fitness that continues for months to years in some individuals. These persistent post-COVID-19 conditions may affect a firefighter's ability to return to work, function at full capacity while at work, and potentially compromise firefighter health and public safety. This review, therefore, explores musculoskeletal, pulmonary, and cardiovascular sequelae post-COVID-19 and the impact of these sequelae on firefighter health and occupational readiness.

FPR1 signaling aberrantly regulates S100A8/A9 production by CD14+FCN1hi macrophages and aggravates pulmonary pathology in severe COVID-19

Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Emerging small-molecule antiviral agents in long COVID prevention.

Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments. These symptoms, emerging one to 2months post-infection and persisting for several months, cannot be attributed to other diagnoses. The pathophysiology of long COVID remained elusive; however, emerging studies suggested multiple potential mechanisms, including the reactivation of Epstein-Barr virus, persistent SARS-CoV-2 reservoirs, neuroinflammation, and vascular damage, which may contribute to its development. Long COVID affected multiple organ systems, including respiratory, circulatory, and nervous systems, leading to a range of functional impairments. Additionally, it showed a profound impact on mental health, manifesting as anxiety and depression, which significantly degraded the quality of life. The absence of definitive treatments underscored the importance of prevention. Recent evidence indicated that early antiviral intervention-particularly with small-molecule drugs such as Metformin, Ensitrelvir, Molnupiravir, and Nirmatrelvir-may effectively reduce the incidence of long COVID. This underscored the promising role of small-molecule compounds in mitigating long-term COVID-19 consequences, offering a novel preventive strategy against long COVID and its extensive impacts on patients.

SSRI use during acute COVID-19 and risk of long COVID among patients with depression

BackgroundLong COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.MethodsIn an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.ResultsWe analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).ConclusionsThese findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Herpesvirus Antibody Response and Occurrence of Symptoms in Acute and Post-Acute COVID-19 Disease.

Knowledge about the underlying causes of the individual occurrence of symptoms during acute COVID-19 disease and during the post-acute sequelae of COVID-19 is limited. In a German COVID-19 follow-up study, we assessed whether elevated antibody responses to herpesviruses were associated with symptom occurrence in acute COVID-19 disease (n = 96 participants) and during 20 months of follow-up (n = 62 participants). Serum samples were analyzed for their antibodies to herpes simplex virus (HSV)-1 and -2, Epstein-Barr virus (EBV), and Cytomegalovirus (CMV) using fluorescent bead-based multiplex serology. The association of herpesvirus antibodies with symptom occurrence (fatigue, fever, dyspnea, decrease in taste, concentration problems) was assessed using multivariate logistic regression models. High EBV antibody levels were significantly associated with a more than fourfold increased odds of experiencing fatigue during acute COVID-19 disease and during follow-up. High CMV antibody levels were significantly associated with a more than threefold increased odds of experiencing concentration problems and a decrease in taste during the follow-up. The HSV-1 and -2 antibody levels were not elevated in the individuals that experienced symptoms. In conclusion, our findings indicate that herpesvirus infections, specifically EBV and CMV infections, might play a role in symptom development during acute and post-acute COVID-19 disease. It remains to be elucidated whether the elevated EBV and CMV antibodies determined in our study are indicators of herpesvirus reactivation.

Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy.

No reduced serum serotonin levels in patients with post-acute sequelae of COVID-19.

Approximately 10-20% of patients previously infected with SARS-CoV-2 experience post-acute sequelae of COVID-19 (PASC), presenting with fatigue and neurocognitive dysfunction along various other symptoms. Recent studies suggested a possible role of a virally induced decrease in peripheral serotonin concentration in the pathogenesis of PASC. We set out to verify this finding in an independent and well-defined cohort of PASC patients from our post-COVID-19 outpatient clinic. We performed a retrospective case-control study including 34 confirmed PASC patients and 14 healthy controls. Clinical assessment encompassed physician examination as well as questionnaire based evaluation. Eligibility required ongoing symptoms for at least 6 months post-PCR-confirmed infection, relevant fatigue (CFS ≥ 4), and no other medical conditions. Serum serotonin was determined by LC-MS/MS technique. Serum serotonin levels in PASC patients did not significantly differ from healthy controls. Most subjects had normal serotonin levels, with no subnormal readings. Subgroup analyses showed no significant differences in serotonin levels based according to predominant fatigue type, high overall fatigue score or depression severity. We postulate that peripheral serotonin is no reliable biomarker for PASC and that it should not be used in routine diagnostic. Therapy of PASC with serotonin-reuptake inhibitors or tryptophane supplementation should not be based solely on the assumption of lowered serotonin levels.

Long-term COVID-19 sequelae by Theta and SARS-CoV-2 variants in a Philippine cohort.

Millions have been infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since its emergence in 2019, but most patients make a full recovery. The long-term consequences of the infection are anticipated to unravel in the succeeding years with reports of patients experiencing chronic, debilitating sequelae post-infection commonly referred to as Long COVID. Various Variants of Concern (VoCs) have emerged as the SARS-CoV-2 virus evolved displaying increased infectivity and immune evasiveness. We investigate whether the infecting VoCs affect the sequelae of Long COVID in a Philippine cohort. SARS-CoV-2 cases confirmed using RT-PCR followed by Next Generation Sequencing were identified from selected regions of the Philippines and recruited through a retrospective-prospective cohort design. Participants were divided based on the initial infecting VoC or Variant of Interest (VoI) and were subsequently interviewed regarding the presence, intensity, and frequency of key Long COVID symptoms, and followed up on two more separate sessions at least three (3) months apart for a total of three (3) data collection points (S1, S2, S3) to document changes in symptoms throughout the year-long study period. Long COVID symptoms were reported in 88, 82, and 68% of participants in S1, S2, and S3, respectively, showing declining incidence with elapsed time since the first reported infection. General symptoms including headache, fatigue, and post-exertional malaise were the most frequently reported symptoms, while neuropsychiatric symptoms were the second most frequently reported symptoms. In all three (3) sessions, intermittent brain fog, fatigue, and headache were the most frequently reported symptoms in all SARS-CoV-2 variant cohorts. Factors such as age, sex, comorbidities, and disease severity influenced symptom frequency, providing insight into the risk factors that contribute to the prevalence of this disease. A large proportion (>68%) of cases in this Philippine cohort previously infected with different SARS-CoV-2 variants presented with long-term complications of COVID-19 characterized by a highly heterogeneous set of debilitating symptoms. The study highlights the need for long-term monitoring of Long COVID and its impact on human health and the need for our health systems to adopt policy response strategies.

HERV-W ENV transcription in B cells predicting symptomatic COVID-19 and risk for long COVID can express a full-length protein despite stop codon in mRNA from chromosome X via a ribosome readthrough.

The human genome comprises 8% of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-W ENV-U3R RNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level. Results not only confirm HERV-W ENV RNA origin in these patients but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.

In adults with postacute sequelae of COVID-19, nirmatrelvir-ritonavir did not improve symptoms at 10 wk.

Geng LN, Bonilla H, Hedlin H, et al. Nirmatrelvir-ritonavir and symptoms in adults with postacute sequelae of SARS-CoV-2 infection: the STOP-PASC randomized clinical trial. JAMA Intern Med. 2024;184:1024-1034. 38848477.

S1705 Hepatobiliary Sequelae of COVID-19: Investigating Post-Infection Complications

S1705 Hepatobiliary Sequelae of COVID-19: Investigating Post-Infection Complications

Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study.

To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detection with postacute sequelae of COVID-19 (PASC) symptoms. Plasma and serum samples were collected from adults participating in four independent studies at different time points, ranging from several days up to 14months post-SARS-CoV-2 infection. The primary outcome measure was to quantify SARS-CoV-2 antigens, including the S1 subunit of spike, full-length spike, and nucleocapsid, in participant samples. The presence of 34 commonly reported PASC symptoms during the postacute period was determined from participant surveys or chart reviews of electronic health records. Of the 1569 samples analysed from 706 individuals infected with SARS-CoV-2, 21% (95% CI, 18-24%) were positive for either S1, spike, or nucleocapsid. Spike was predominantly detected, and the highest proportion of samples was spike positive (20%; 95% CI, 18-22%) between 4 and 7months postinfection. In total, 578 participants (82%) reported at least one of the 34 PASC symptoms included in our analysis ≥1month postinfection. Cardiopulmonary, musculoskeletal, and neurologic symptoms had the highest reported prevalence in over half of all participants, and among those participants, 43% (95% CI, 40-45%) on average were antigen-positive. Among the participants who reported no ongoing symptoms (128, 18%), antigen was detected in 28 participants (21%). The presence of antigen was associated with the presence of one or more PASC symptoms, adjusting for sex, age, time postinfection, and cohort (OR, 1.8; 95% CI, 1.4-2.2). The findings of this multicohort study indicate that SARS-CoV-2 antigens can be detected in the blood of a substantial proportion of individuals up to 14months after infection. While approximately one in five asymptomatic individuals was antigen-positive, roughly half of all individuals reporting ongoing cardiopulmonary, musculoskeletal, and neurologic symptoms were antigen-positive.

Individuals With Post-Acute Sequelae Of COVID-19 Have Impaired Endothelial Function, But Combined Exercise Training Restores Endothelial Function

Individuals With Post-Acute Sequelae Of COVID-19 Have Impaired Endothelial Function, But Combined Exercise Training Restores Endothelial Function

Long Covid: a global health issue – a prospective, cohort study set in four continents

IntroductionA proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise...