Phenotyping of acute and persistent COVID-19 features in the outpatient setting: exploratory analysis of an international cross-sectional online survey

Abstract BACKGROUND Long COVID, defined as presence of COVID-19 related symptoms 28 days or more after the onset of acute SARS-CoV-2 infection, is an emerging challenge to healthcare systems. The objective of this study was to phenotype recovery trajectories of non-hospitalized COVID-19 individuals. METHODS We performed an international, multi-center, exploratory online survey study on demographics, comorbidities, COVID-19 symptoms and recovery status of non-hospitalized SARS-CoV-2 infected adults (Austria: n=1157), and Italy: n= 893). RESULTS Working age subjects (Austria median: 43 yrs (IQR: 31 – 53), Italy: 45 yrs (IQR: 35 – 55)) and females (65.1% and 68.3%) predominated the study cohorts. Course of acute COVID-19 was characterized by a high symptom burden (median 13 (IQR: 9 – 18) and 13 (7 – 18) out of 44 features queried), a 47.6 – 49.3% rate of symptom persistence beyond 28 days and 20.9 – 31.9% relapse rate. By cluster analysis, two acute symptom phenotypes could be discerned: the non-specific infection phenotype and the multi-organ phenotype (MOP), the latter encompassing multiple neurological, cardiopulmonary, gastrointestinal and dermatological features. Clustering of long COVID subjects yielded three distinct subgroups, with a subset of 48.7 – 55 % long COVID individuals particularly affected by post-acute MOP symptoms. The number and presence of specific acute MOP symptoms and pre-existing multi-morbidity was linked to elevated risk of long COVID. CONCLUSION The consistent findings of two independent cohorts further delineate patterns of acute and post-acute COVID-19 and emphasize the importance of symptom phenotyping of home-isolated COVID-19 patients to predict protracted convalescence and to allocate medical resources. Key Points Question Which acute symptom patterns of acute COVID-19 are associated with prolonged symptom persistence, symptom relapse or physical performance impairment? Findings In this multicenter international comparative survey study on non-hospitalized SARS- CoV-2 infected adults (Austria: n = 1157, Italy: n = 893) we identified distinct and reproducible phenotypes of acute and persistent features. Acute multi-organ symptoms including neurological and cardiopulmonary manifestations are linked to elevated risk of long COVID. Meaning These findings suggest to employ symptom phenotyping of home-isolated COVID-19 patients to predict protracted convalescence and to allocate medical resources.