Dataset Information

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

ABSTRACT:

Background

Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs.

Methods

This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677.

Findings

Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively).

Interpretation

Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials.

Funding

The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.

SUBMITTER: Gentilotti E

PROVIDER: S-EPMC10466236 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Gentilotti Elisa E Górska Anna A Tami Adriana A Gusinow Roy R Mirandola Massimo M Rodríguez Baño Jesús J Palacios Baena Zaira R ZR Rossi Elisa E Hasenauer Jan J Lopes-Rafegas Iris I Righi Elda E Caroccia Natascia N Cataudella Salvatore S Pasquini Zeno Z Osmo Thomas T Del Piccolo Lidia L Savoldi Alessia A Kumar-Singh Samir S Mazzaferri Fulvia F Caponcello Maria Giulia MG de Boer Gerolf G Hara Gabriel Levy GL De Nardo Pasquale P Malhotra Surbhi S Canziani Lorenzo Maria LM Ghosn Jade J Florence Aline-Marie AM Lafhej Nadhem N van der Gun Bernardina T F BTF Giannella Maddalena M Laouénan Cédric C Tacconelli Evelina E

EClinicalMedicine 20230721

<h4>Background</h4>Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs.<h4>Methods</h4>This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical featu ...[more]

PMID: 37654668

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Project description:PurposePost-Covid-19 syndrome is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The most common symptoms include reduced exercise tolerance and capacity, fatigue, neurocognitive problems, muscle pain and dyspnea. The aim of our work was to investigate exercise capacity and markers of subjective wellbeing and their independent relation to post-COVID-19 syndrome.Patients and methodsWe examined a total of 69 patients with post-COVID-19 syndrome (23 male/46 female; age 46±12 years; BMI 28.9±6.6 kg/m2) with fatigue and a score ≥22 in the Fatigue Assessment Scale (FAS). We assessed exercise capacity on a cycle ergometer, a 6-minute walk test, the extent of fatigue (FAS), markers of health-related quality of life (SF-36 questionnaire) and mental health (HADS).ResultsOn average the Fatigue Assessment Scale was 35.0±7.4 points. Compared with normative values the VO2max/kg was reduced by 8.6±5.8 ml/min/kg (27.7%), the 6MWT by 71±96 m (11.9%), the health-related quality of life physical component score by 15.0±9.0 points (29.9%) and the mental component score by 10.6±12.8 points (20.6%). Subdivided into mild fatigue (FAS score 22-34) and severe fatigue (FAS score ≥35), patients with severe fatigue showed a significant reduction of the 6-minute walk test by 64±165 m (p<0.01) and the health-related quality of life physical component score by 5.8±17.2 points (p = 0.01). In multiple regression analysis age (β = -0.24, p = 0.02), sex (β = 0.22, p = 0.03), mental (β = -0.51, p<0.01) and physical (β = -0.44, p<0.01) health-related quality of life and by trend the 6-minute walk test (β = -0.22, p = 0.07) were associated with the FAS.ConclusionPatients with post-COVID-19 syndrome show reduced maximal and submaximal physical performance as well as limitations in quality of life, particularly pronounced in the physical components. These results are essentially influenced by the severity of fatigue and implicating the need for targeted treatments.

Project description:Prior attempts at identifying outcome determinants associated with bloodstream infection have employed a priori determined classification schemes based on readily identifiable microbiology, infection site, and patient characteristics. We hypothesized that even amongst this heterogeneous population, clinically relevant groupings can be described that transcend old a priori classifications.We applied cluster analysis to variables from three domains: patient characteristics, acuity of illness/clinical presentation and infection characteristics. We validated our clusters based on both content validity and predictive validity.Among 3715 patients with bloodstream infections from Barnes-Jewish Hospital (2008-2015), the most stable cluster arrangement occurred with the formation of 4 clusters. This clustering arrangement resulted in an approximately uniform distribution of the population: Cluster One "Surgical Outside Hospital Transfers" (21.5%), Cluster Two "Functional Immunocompromised Patients" (27.9%), Cluster Three "Women with Skin and Urinary Tract Infection" (28.7%) and Cluster Four "Acutely Sick Pneumonia" (21.8%). Staphylococcus aureus distributed primarily to Clusters Three (40%) and Four (25%), while nonfermenting Gram-negative bacteria grouped mainly in Clusters Two and Four (31% and 30%). More than half of the pneumonia cases occurred in Cluster Four. Clusters One and Two contained 33% and 31% respectively of the individuals receiving inappropriate antibiotic administration. Mortality was greatest for Cluster Four (33.8%, 27.4%, 19.2%, 44.6%; P < .001), while Cluster One patients were most likely to be discharged to a nursing home.Our results support the potential for machine learning methods to identify homogenous groupings in infectious diseases that transcend old a priori classifications. These methods may allow new clinical phenotypes to be identified potentially improving the severity staging and development of new treatments for complex infectious diseases.

Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

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