Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes

Nature Medicine, Год журнала: 2022, Номер 29(1), С. 226 - 235

Опубликована: Дек. 1, 2022

Abstract The post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum symptoms and signs that are persistent, exacerbated or newly incident in the period after acute infection. Most studies have examined these conditions individually without providing evidence on co-occurring conditions. In this study, we leveraged electronic health record data two large cohorts, INSIGHT OneFlorida+, from national Patient-Centered Clinical Research Network. We created development cohort validation OneFlorida+ including 20,881 13,724 patients, respectively, who were infected, investigated their diagnoses 30–180 days documented Through machine learning analysis over 137 conditions, identified four reproducible PASC subphenotypes, dominated by cardiac renal (including 33.75% 25.43% patients cohorts); respiratory, sleep anxiety (32.75% 38.48%); musculoskeletal nervous system (23.37% 23.35%); digestive respiratory (10.14% 12.74%) sequelae. These subphenotypes associated with distinct patient demographics, underlying before phase severity. Our study provides insights into heterogeneity may inform stratified decision-making management

Язык: Английский

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Generalisable long COVID subtypes: findings from the NIH N3C and RECOVER programmes

EBioMedicine, Год журнала: 2022, Номер 87, С. 104413 - 104413

Опубликована: Дек. 21, 2022

Stratification of patients with post-acute sequelae SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, COVID is incompletely understood and characterised by a wide range manifestations that are difficult to analyse computationally. Additionally, the generalisability machine learning classification COVID-19 outcomes has rarely been tested.

Язык: Английский

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Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(15)

Опубликована: Июль 31, 2022

SARS-CoV-2–infected individuals may suffer a multi–organ system disorder known as "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype. Acute COVID-19 correlates with biomarkers systemic inflammation, hypercoagulability, comorbidities that less prominent in PASC. Macrovessel thrombosis, hallmark acute COVID-19, frequent Female sex at birth associated reduced risk for progression, but increased Persistent microvascular endotheliopathy cryptic tissue reservoirs has been implicated PASC pathology. Autoantibodies, localized reactivation latent pathogens also be involved, potentially leading to documented multiple tissues. Diagnostic assays illuminating possible therapeutic targets discussed.

Язык: Английский

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Long COVID: a clinical update

The Lancet, Год журнала: 2024, Номер 404(10453), С. 707 - 724

Опубликована: Июль 31, 2024

Язык: Английский

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Cellular and molecular biomarkers of long COVID: a scoping review

EBioMedicine, Год журнала: 2023, Номер 91, С. 104552 - 104552

Опубликована: Апрель 8, 2023

Язык: Английский

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Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort

EClinicalMedicine, Год журнала: 2023, Номер 62, С. 102107 - 102107

Опубликована: Июль 21, 2023

Lack of specific definitions clinical characteristics, disease severity, and risk preventive factors post-COVID-19 syndrome (PCS) severely impacts research discovery new therapeutics drugs.This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- in-patients followed at 3-, 6-, 12-month diagnosis, with assessment biochemical features, antibody (Ab) response, Variant Concern (VoC), physical mental quality life (QoL). Outcome interest identification protective PCS by phenotype, setting, severity disease, treatment, vaccination status. We used SF-36 questionnaire assess evolution QoL index during follow-up unsupervised machine learning algorithms (principal component analysis, PCA) explore symptom clusters. Severity defined phenotype QoL. also generalized linear models analyse the impact on associated factors. CT registration number: NCT05097677.Among 1796 patients enrolled, 1030 (57%) suffered least one 12-month. PCA identified 4 phenotypes: chronic fatigue-like (CFs: fatigue, headache memory loss, 757 patients, 42%), respiratory (REs: cough dyspnoea, 502, 23%); pain (CPs: arthralgia myalgia, 399, 22%); neurosensorial (NSs: alteration taste smell, 197, 11%). Determinants phenotypes were different (all comparisons p < 0.05): being female increased CPs, NSs, CFs; pulmonary diseases REs; neurological symptoms diagnosis REs, oxygen therapy CFs gastrointestinal CFs. Early treatment infection monoclonal Ab phenotypes), corticosteroids for mild/severe cases (NSs), (CPs) less likely be 0.05). Highest reduction detected REs CPs (43.57 43.86 vs 57.32 PCS-negative controls, 0.001). Female sex (p 0.001), = 0.034) renal complications 0.002) acute increase severe (QoL <50). Vaccination early reduced 0.01 0.03, respectively).Our provides evidence suggesting that can classified QoL, underlying possible pathogenic mechanisms. each PCS. These results might help designing pathogenesis studies selecting high-risk inclusion therapeutic management trials.The received funding Horizon ORCHESTRA project, grant 101016167; Netherlands Organisation Health Research Development (ZonMw), 10430012010023; Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium French Ministry Health, PHRC 20-0424.

Язык: Английский

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Long COVID: a review and proposed visualization of the complexity of long COVID

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 20, 2023

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose visual description the complexity COVID its pathogenesis that can be used by researchers, clinicians, public health officials to guide global effort toward an improved understanding eventual mechanism-based provision care afflicted patients. The proposed visualization framework for should evidence-based, dynamic, modular, systems-level approach condition. Furthermore, further research such could establish strength relationships between pre-existing conditions (or risk factors), biological mechanisms, resulting clinical phenotypes outcomes COVID. Notwithstanding significant contribution disparities in access social determinants have on disease course long our model focuses primarily mechanisms. Accordingly, sets out scientific, clinical, efforts better understand abrogate burden imposed

Язык: Английский

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Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study

The Lancet Regional Health - Europe, Год журнала: 2023, Номер 33, С. 100724 - 100724

Опубликована: Сен. 5, 2023

At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or "Long COVID". The clinical presentation PCC is heterogeneous, its pathogenesis being deciphered, and objective, validated biomarkers are lacking. It unknown if a single entity heterogeneous syndrome with overlapping pathophysiological basis. large US RECOVER study identified four clusters according to their presenting symptoms. However, long-term implications remain unknown.We conducted 2-year prospective cohort COVID-19, including individuals fulfilling WHO definition full recovery. We systematically collected symptoms using prespecified questionnaires performed additional diagnostic imaging tests when needed. Factors associated were modelled logistic regression. Unsupervised clustering analysis was used group recovery direct acyclic graph approach.The included 548 individuals, 341 PCC, followed for median 23 months (IQR 16.5-23.5), 207 fully recovered. In model best fit, who male had tertiary studies less likely whereas history headache, presence tachycardia, fatigue, neurocognitive neurosensitive complaints dyspnea at diagnosis predicted development PCC. cluster revealed three symptom an additive number Only 26 (7.6%) recovered from during follow-up; almost all them (n = 24) belonged symptomatic A, dominated mainly by fatigue. Recovery more in male, required ICU admission, cardiovascular comorbidities, hyporexia and/or smell/taste alterations acute COVID-19. Subjects muscle pain, impaired attention, dyspnea, conversely, recover PCC.Preexisting medical socioeconomic factors, as well symptoms, extremely rare first 2 years, posing major challenge healthcare systems.Fundació Lluita contra les Infeccions.

Язык: Английский

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Characterization of post-COVID syndromes by symptom cluster and time period up to 12 months post-infection: A systematic review and meta-analysis

International Journal of Infectious Diseases, Год журнала: 2023, Номер 134, С. 1 - 7

Опубликована: Май 6, 2023

ObjectivesThe objective of this study was to characterize post-COVID condition symptoms and symptom clusters, their duration, prevalence.MethodsWe conducted a systematic review random-effects meta-analysis studies reporting post-COVID-19 respectively. We searched MEDLINE (via PubMed), Scopus, Web Science, Science Direct, Google Scholar, EBSCOhost, EMBASE, PsycINFO, Cochrane Library, Mednar for literature on the up August 2022.ResultsIn 76 included studies, we found that although most were reported less frequently 7-12 months after infection compared earlier, over 20% patients at least one condition-compatible symptom. In seven neurological clustering consistently identified, followed by cardiorespiratory systemic/inflammatory.ConclusionPost-COVID provides direction research into etiology, diagnosis, management conditions. Studies clusters remain rare due focus individual reporting. should replace accelerate our understanding emerging public health issue.

Язык: Английский

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Mechanisms of long COVID and the path toward therapeutics

Cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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