Long COVID science, research and policy

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 2148 - 2164

Published: Aug. 1, 2024

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system be severely disabling. The cumulative global incidence long around 400 million individuals, which estimated to have an annual economic impact approximately $1 trillion-equivalent about 1% economy. Several mechanistic pathways are implicated in COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement endothelial inflammation microbiome dysbiosis. devastating impacts on individual lives and, due its complexity prevalence, also has major ramifications for systems economies, even threatening progress toward achieving Sustainable Development Goals. Addressing challenge requires ambitious coordinated-but so far absent-global research policy response strategy. In this interdisciplinary review, we provide synthesis state scientific evidence assess human health, systems, economy metrics, forward-looking roadmap.

Language: Английский

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Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study

PLoS Medicine, Journal Year: 2025, Volume and Issue: 22(1), P. e1004511 - e1004511

Published: Jan. 23, 2025

Background Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance sleep problems. The long-term prognosis of post-acute sequelae COVID-19/post-COVID-19 (PCS) is unknown, data finding correlating organ dysfunction pathology with self-reported symptoms in patients non-recovery from PCS scarce. We wanted to describe clinical characteristics diagnostic findings among persisting for >1 year assessed risk factors persistence versus improvement. Methods This nested population-based case-control study included subjects aged 18–65 years ( n = 982) age- sex-matched control without 576) according an earlier questionnaire (6–12 months after infection, phase 1) consenting provide follow-up information undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, laboratory testing four university centres southwestern Germany (phase 2, another 8.5 [median, range 3–14 months] 1). mean age the participants was 48 years, 65% were female. At 67.6% at 1 developed persistent PCS, whereas 78.5% recovered remained free related PCS. Improvement associated mild index previous full-time employment, educational status, no specialist consultation not attending a rehabilitation programme. development new initially intercurrent secondary SARS-CoV-2 status. Patients less frequently never smokers (61.2% 75.7%), more obese (30.2% 12.4%) higher values body mass (BMI) fat, had lower status (university entrance qualification 38.7% 61.5%) than continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness anxiety/depression/sleep predominant symptom clusters. Exercise intolerance post-exertional malaise (PEM) >14 h compatible myalgic encephalomyelitis/chronic fatigue reported by 35.6% 11.6% patients, respectively. In analyses adjusted sex-age class combinations, centre qualification, significant differences between those recovery observed performance three different tests, scores perceived stress, subjective cognitive disturbances, dysautonomia, depression anxiety, quality, quality life. handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] 42.5 CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [27.3, 28.4]] 31.0 [30.3, 31.6]] ml/min/kg weight) ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [28.3, 29.2]] 27.1 [26.6, 27.7]]) significantly reduced relative group adjustment centre, education, BMI, smoking use beta blocking agents. There measures systolic diastolic cardiac function rest, level N-terminal brain natriuretic peptide blood levels other measurements (including complement activity, markers Epstein–Barr virus [EBV] reactivation, inflammatory coagulation markers, serum cortisol, adrenocorticotropic hormone dehydroepiandrosterone sulfate). Screening viral (PCR stool samples spike antigen plasma) subgroup negative. Sensitivity (pre-existing illness/comorbidity, obesity, medical care infection) revealed similar findings. PEM pain worse results almost all tests. A limitation that we objective on exercise capacity cognition before infection. addition, did unable attend clinic whatever reason illness, immobility social deprivation exclusion. Conclusions this study, majority working recover second their illness. Patterns essentially similar, dominated complaints. Despite signs deficits capacity, there major investigations, our do support persistence, EBV adrenal insufficiency increased turnover pathophysiologically relevant history disease might help stratify cases severity.

Language: Английский

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Exploring the Complexities of Long COVID

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1060 - 1060

Published: June 30, 2024

Since the emergence of SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 deaths have been reported globally. Despite most individuals recovering within four weeks, Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such age, gender, comorbidities, initial severity, vaccine interactions, delves into potential mechanisms, including immune responses, viral persistence, gut dysbiosis. Moreover, we conclude women, advanced non-vaccination, low socioeconomic status all appear be risk factors. The reasons these differences are still not fully understood likely involve a complex relationship between social, genetic, hormonal, other Furthermore, with seem more endure economic hardship due persistent symptoms. In summary, our findings further illustrate multifaceted nature COVID underscore importance understanding factors mechanisms needed effective therapeutic strategies interventions.

Language: Английский

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Cardiovascular events following coronavirus disease 2019 vaccination in adults: a nationwide Swedish study

European Heart Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Background and Aims While the rationale for coronavirus disease 2019 (COVID-19) vaccination is to reduce complications overall mortality, some cardiovascular from vaccine itself have been demonstrated. Myocarditis pericarditis are recognized as rare acute adverse events after mRNA vaccines in young males, while evidence regarding other remains limited inconsistent. This study assessed risks of several cerebrovascular a Swedish nationwide register-based cohort. Methods Post-vaccination risk myocarditis/pericarditis, dysrhythmias, heart failure, myocardial infarction, (transient ischaemic attack stroke) windows each dose were among all adults (n = 8 070 674). Hazard ratios (HRs) with 95% confidence intervals (95% CIs) compared unvaccinated estimated Cox regression models adjusted potential confounders. Results For most studied outcomes, decreased post-vaccination observed, especially three (HRs ranging .69 .81), replicating increased myocarditis 1–2 weeks COVID-19 vaccination. Slightly risks, similar across vaccines, observed extrasystoles [HR 1.17 CI 1.06–1.28) one HR 1.22 1.10–1.36) two, stronger elderly males] but not arrhythmias transient 1.13 1.05–1.23), mainly elderly] stroke. Conclusions Risk myopericarditis (mRNA only), extrasystoles, was transiently vaccination, full substantially reduced more severe COVID-19-associated underscoring protective benefits complete

Language: Английский

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Targeting the SARS-CoV-2 reservoir in long COVID

The Lancet Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Viral Variants, Vaccinations, and Long Covid — New Insights

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(6), P. 561 - 562

Published: July 17, 2024

Language: Английский

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Spike and nucleocapsid antibody dynamics following SARS‐CoV‐2 infection and vaccination: Implications for sourcing COVID‐19 convalescent plasma from routinely collected blood donations

Transfusion, Journal Year: 2024, Volume and Issue: 64(11), P. 2063 - 2074

Published: Oct. 7, 2024

Abstract Background COVID‐19 convalescent plasma (CCP) remains a treatment option for immunocompromised patients; however, the current FDA qualification threshold of ≥200 BAU/mL spike antibody appears to be relatively low. We evaluated levels binding (bAb) and neutralizing antibodies (nAb) on serial samples from repeat blood donors who were vaccinated and/or infected inform criteria qualifying CCP routinely collected components. Methods Donors categorized into four groups: (1) infected, then vaccinated, (2) during delta, or (3) omicron waves, (4) without infection. IgG Spike total Nuclecapsid bAb measured, along with S variants nAb titers using reporter viral particle neutralization. Results Mean peaks after infection alone lower than primary booster vaccinations, higher delta in previously donors. Half‐lives ranged 34 66 days first infection/vaccination events up 108 second events. The similar across different variants, except omicron, which lower. Better correlations observed at (hybrid immunity) threshold. Discussion Routine donations hybrid immunity had high potent activity 3–6 months In (>4000 BAU/mL) IgG, >95% (>500) against ancestral variant S, regardless symptoms. These findings provide basis test‐based routine donations.

Language: Английский

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Translating insights into therapies for Long Covid

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(773)

Published: Nov. 13, 2024

Long Covid is defined by a wide range of symptoms that persist after the acute phase severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other reported. Symptom range, duration, severity are highly variable partially overlap myalgic encephalomyelitis/chronic fatigue post-acute infectious syndromes, highlighting opportunities to define shared mechanisms pathogenesis. Potential diverse, including persistence viral reservoirs, dysregulated immune responses, direct damage tissues targeted SARS-CoV-2, inflammation driven reactivation latent infections, vascular endothelium activation or subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, microbiota dysbiosis. The heterogeneity baseline characteristics people Covid, as well varying states immunity therapies given at time infection, have made etiologies difficult determine. Here, we examine progress on preclinical models for review being in clinical trials, need large human studies further development better understand Covid. Such will inform trials treatments benefit those living this condition.

Language: Английский

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Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: population-based, nested case-control study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 22, 2024

Abstract Objective To assess risk factors for persistence vs improvement and to describe clinical characteristics diagnostic evaluation of subjects with post-acute sequelae COVID-19/post-COVID-19 syndrome (PCS) persisting more than one year. Design Nested population-based case-control study. Setting Comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, laboratory testing in four university health centres southwestern Germany (2022). Participants PCS cases aged 18 65 years (n=982) age sex-matched controls without (n=576) according an earlier questionnaire study (six 12 months after acute infection, phase 1) consenting provide follow-up information undergo assessment (phase 2, another 8.5 [median] 1). Main outcome measures Relative frequencies symptoms problems distribution symptom scores test results between persistent controls. Additional analysis included predictors changing case or control status over time adjustments potentially confounding variables. Results At the examination 2), 67.6% initial remained cases, whereas 78.5% continued report no related PCS. In adjusted analyses, among were mild index previous full-time employment, educational status, specialist consultation not attending a rehabilitation programme. Among controls, new worsening development intercurrent secondary SARS-CoV-2 infection status. less frequently never smokers, had higher values BMI body fat, lower Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness anxiety/depression/sleep predominant clusters, exercise intolerance post-exertional malaise >14 h (PEM) compatible ME/CFS (according Canadian consensus criteria) reported by 35.6% 11.6% respectively. significant differences stable (at 2) observed performances, perceived stress subjective cognitive disturbances, indicating dysautonomia, depression anxiety, sleep quality, fatigue, quality life. handgrip strength, maximal oxygen consumption, ventilator efficiency significantly reduced. However, there systolic diastolic cardiac function, level pro-BNP blood levels other measurements (including complement activity, serological markers EBV reactivation, inflammatory coagulation markers, cortisol, ACTH DHEA-S serum levels). Screening viral (based on PCR stool samples spike antigen plasma subgroup cases) was negative. Sensitivity analyses (pre-existing illness/comorbidity, obesity, PEM, medical care infection) revealed similar findings showed that PEM pain worse almost all tests. Conclusions This nested demonstrates majority do recover second year their illness, patterns remaining essentially similar, nonspecific dominated complaints. We found objective signs deficits reduced capacity likely be unrelated primary pulmonary dysfunction some but major pathology investigations. A history which associated severe as well disease may pragmatic means stratify severity. What is already known this topic Self-reported following have commonly been described persist months. They typically include relatively non-specific complaints such exertional dyspnoea, concentration memory disturbance problems. The incidence post-COVID-19 varying sociodemographic variables, pre-existing comorbidities, severity factors. long-term prognosis unknown differ different clusters. Evidence measurable single multiple organ correlation self-reported patients non-recovery from described. adds describes (need for) programme (the latter probably due reverse causation) PCS, changes clusters After comprehensive correlated symptoms, detected often longer lasting malaise, both physical (diminished consumption ventilatory efficiency), performances while investigations adjustment possible confounders.

Language: Английский

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Evaluation of Inflammatory Markers and Clinical Outcomes in COVID-19 Patients with Concurrent Clostridioides difficile Infection: A Comparative Cohort Analysis

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 111 - 111

Published: Jan. 6, 2025

Co-infection with Clostridioides difficile (C. difficile) in COVID-19 patients has emerged as a clinical challenge associated increased morbidity and mortality. While both infections elicit systemic inflammation, the interplay between inflammatory markers, disease severity, outcomes concurrent C. infection remains poorly characterized. This study aimed to evaluate status of hospitalized COVID-19, without co-infection, identify markers most predictive severe disease. We conducted retrospective cohort 200 adults confirmed whom 92 had laboratory-confirmed infection. Baseline demographic data, comorbidities, (C-reactive protein [CRP], interleukin-6 [IL-6], ferritin, neutrophil-to-lymphocyte ratio [NLR], platelet count, albumin, derived indices such CRP-to-Albumin Ratio [CAR] Prognostic Nutritional Index [PNI]) were recorded. Clinical included ICU admission, need for mechanical ventilation, length stay, in-hospital Patients co-infection significantly elevated (CRP, IL-6, NLR) higher CAR, alongside lower PNI, compared those alone (p < 0.001). Inflammatory correlated strongly severity: CAR low PNI odds admission mortality Multivariate analysis identified status, independent predictors outcomes. is an intensified response worse Among evaluated robust Timely recognition use targeted anti-inflammatory supportive therapies may improve patient management. Future studies should expand on these findings optimize care guide therapeutic strategies.

Language: Английский

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