Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.
Bibliographical noteFunding Information:
This work was supported by the Department for International Development and Wellcome Trust [215091/Z/18/Z]; the Bill and Melinda Gates Foundation [OPP1209135]. Country-specific support was provided by the Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity [OV2170359]; the Health Research Board Ireland [CTN Award 2014-012]; National Institute for Health Research (NIHR) [award CO-CIN-01]; the Medical Research Council (MRC) [grant MC_PC_19059]; the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907]; NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927]; Liverpool Experimental Cancer Medicine Centre [grant reference C18616/A25153]; NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013]; EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) [FP7 project 602525]; National Institutes of Health (NIH) [UL1TR002240]; and NIHR Clinical Research Network infrastructure support. We acknowledge the generous support of all ISARIC Partners who have contributed data and expertise to this analysis, with or without dedicated funding. The views expressed are those of the authors and not necessarily those of the funders or institutions listed above.
We are extremely grateful to the frontline clinical and research staff and volunteers, who collected this data in challenging circumstances, and the generosity of the patients and their families for their individual contributions in these difficult times. This work uses data provided by patients and collected by the health institutions and authorities in each country. In the UK, this study involves the National Health Service as part of their care and support #DataSavesLives. We also acknowledge the support of Jeremy J Farrar, Nahoko Shindo, Devika Dixit, Nipunie Rajapakse, Andrew Davison, Lyndsey Castle, Martha Buckley, Debbie Malden, Katherine Newell, Kwame O’Neill, Emmanuelle Denis, Claire Petersen, Scott Mullaney, Sue MacFarlane, Nicole Maziere, Julien Martinez, Oslem Dincarslan, Annette Lake and the Irish Critical Care Trials Group. We appreciate the strong collaboration of the WHO Clinical Data Platform Team, including Silvia Bertagnolio, Soe Soe Thwin, and Janet Diaz.
M. Cheng declares grants from McGill Interdisciplinary Initiative in Infection and Immunity, and Canadian Institutes of Health Research; and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and nplex biosciences (as a member of the scientific advisory board); M. Cummings and M. O'Donnell participated as investigators for completed and ongoing clinical trials evaluating the efficacy and safety of remdesivir (sponsored by Gilead Sciences) and convalescent plasma (sponsored by Amazon), in hospitalized patients with COVID-19—support for this work is paid to Columbia University; J. C. Holter declared grants from Research Council of Norway [grant 312780], and Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, during the conduct of the study; A.Kimmoun declared personal fees (payment for lectures) from Baxter, Aguettant, Aspen; D. Kumar declared grants and personal fees from Roche, GSK and Merck, and personal fees from Pfizer and Sanofi; F.X. Lescure declared personal fees (payment for lectures) from Gilead, MSD; and travel/accommodation/meeting expenses from Astellas, Eumedica, MSD; A. Pesenti declared personal fees from Maquet, Novalung/Xenios, Baxter, and Boehringer Ingelheim; S. Shrapnel reported grants from Prince Charles Hospital Foundation during the conduct of the study, and concurrently performed data analytics for the COVID-19 Critical Care Consortium; R. Tedder reports grants from MRC/UKRI during the conduct of the study, and has a patent United Kingdom Patent Application No. 2014047.1 “SARS-CoV-2 antibody detection assay” issued; J. Troost declared personal fees from General Electric and Procter and Gamble.
© 2021, The Author(s).
- Case definition