Symptom-based case definitions for COVID-19: Time and geographical variations for detection at hospital admission among 260,000 patients.

Case definitions are used to guide clinical practice, surveillance and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Patients were assessed using the Centers for Disease Control (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO) and UK Health Security Agency (UKHSA) case definitions by age, region and time. Case fatality ratios (CFRs) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test result were excluded. A total of 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC) and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients who met the case definitions. However, when more patients did not meet the case definition, the CFR increased. The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions, risking delayed medical care. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

Informations de copyright

© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

Déclaration de conflit d'intérêts

Allavena, C. declares personal fees from ViiV Healthcare, MSD, Janssen and Gilead, all outside the submitted work. Andréjak, C. declares personal fees for lecture from Astra Zeneca, outside the submitted work. Antonelli, M. declares unrestricted research grants from GE and Estor/Toray and Board participation from Pfizer and Shionogi. All unrelated to the present work. Borie, R. declares personal fees for lecture from Roche, Sanofi and Boehringer Ingelheim, outside the submitted work. Bosse, Hans Martin is co‐investigator for placebo studies in infants and children in clinical trials by Actelion/Janssen (Johnson & Johnson), outside the submitted work. Cheng, M. declares grants from McGill Interdisciplinary Initiative in Infection and Immunity and grants from Canadian Institutes of Health Research, during the conduct of the study; and personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and personal fees from nplex biosciences (as a member of the scientific advisory board), outside the submitted work. He is the co‐founder of Kanvas Biosciences and owns equity in the company. In addition, Cheng, M. reports a patent Methods for detecting tissue damage, graft versus host disease and infections using cell‐free DNA profiling pending, and a patent Methods for assessing the severity and progression of SARS‐CoV‐2 infections using cell‐free DNA pending. Cholley, B. declares personal fees (for lectures and participation to advisory boards) from Edwards, Amomed, Nordic Pharma and Orion Pharma. Claure‐Del Granado, R. declares personal fees (for lectures and participation to advisory boards) from Nova Biomedical and Medtronic, all outside the submitted work. Cruz‐Bermúdez, J. L. declares personal fees from Elsevier for advice, outside the submitted work. Cummings, M. and O'Donnell, M. participated as investigators for clinical trials evaluating the efficacy and safety of remdesivir (sponsored by Gilead Sciences) and convalescent plasma (sponsored by Amazon) in hospitalised patients with COVID‐19. Support for this work is paid to Columbia University. Dalton, H. declares personal fees for medical director of Innovative ECMO Concepts and honorarium from Abiomed/BREETHE Oxi‐1 and Instrumentation Labs and consultant fee from Entegrion Inc., Medtronic and Hemocue. Dyrhol‐Riise, A. M. declares grants from Gilead outside this work. Deplanque, D. declares personal fees from Biocodex, Bristol‐Myers Squibb and Pfizer (advisory boards). Donnelly, C. A. declares research funding from the UK Medical Research Council and the UK National Institute for Health Research. Douglas, J. J. declares personal fees from lectures from Sunovion and Merck and consulting fees from Pfizer. Durante‐Mangoni, E. declares funding via his institution from MSD and Pfizer and personal fees or participation in advisory boards or participation to the speaker's bureau of Roche, Pfizer, MSD, Angelini, Correvio, Nordic Pharma, Bio‐Merieux, Abbvie, Sanofi‐Aventis, Medtronic, Tyrx and DiaSorin. Grasselli, G. declares personal fees from Getinge, Biotest, Draeger Medical, Fisher & Paykel and MSD and unrestricted research grant from MSD and Fisher & Paykel, all outside the submitted work. Gruner, H. declares grants from Bayer outside the submitted work. Guerguerian, A. M. participated as site investigator for the Hospital For Sick Children, Toronto, Canada, as a site through SPRINT‐SARI Study via the Canadian Critical Care Trials Group sponsored in part by the Canadian Institutes of Health Research. Hammond, T. C. declares consulting fees from Regeneron, Pfizer and Agenus. Ho, A. declares grant funding from Medical Research Council UK, Scottish Funding Council ‐ Grand Challenges Research Fund and the Wellcome Trust, outside this submitted work. Holter, J. C. reports grants from Research Council of Norway Grant No. 312780 and from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, during the conduct of the study. Hulot, J. S. reports grants from Bioserenity, Sanofi, Servier and Novo Nordisk and speaker, advisory board or consultancy fees from Amgen, Astra Zeneca, Bayer, Bioserenity, Boerhinger Ingelheim, Bristol‐Myers Squibb, MSD, Novartis, Novo Nordisk and Vifor (all unrelated to the present work). Kalleberg, K. T. is a founder and shareholder of the company Age Labs, which develops epigenetic tests, including one for COVID‐19 severity. Kimmoun, A. declares personal fees (payment for lectures) from Baxter, Aguettant and Aspen. Kumar, D. declares grants and personal fees from Roche, GSK and Merck and personal fees from Pfizer and Sanofi. Kutsogiannis, D. J. declares personal fees for a lecture from Tabuk Pharmaceuticals and the Saudi Critical Care Society. Kutsyna, G. declares the study consulting fee for clinical trial ClinicalTrials.gov Identifier: NCT04762628. Laffey, J. reports that he has received fees for consultancy from GlaxoSmithKline and from Baxter Therapeutics for work outside the scope of this work. Lairez, O. declares grant funding from Pfizer; conference fees from Amicus, GE Healthcare, Novartis, Sanofi‐Genzyme and Takeda‐Shire; and consultancy fees from Alnylam, Amicus, Pfizer and Takeda‐Shire. Lee, J. reports grants from European Commission PREPARE Grant Agreement No. 602525, European Commission RECOVER Grant Agreement No. 101003589 and European Commission ECRAID Grant Agreement 965313 supporting the conduct, co‐ordination and management of the work. Lee, T. C. declares research salary support from les Fonds de recherche du Québec – Santé. Lefèvre, B. declares travel/accommodation/meeting expenses from Mylan and Gilead, all outside the submitted work. Lellouche, F. declares grants from CIHR for COVID‐19 studies, is co‐founder and administrator of Oxynov.inc and declares fees from Fisher & Paykel, Vygon and Novus. Lemaignen, A. declares personal fees (payment for lectures) from MSD and Gilead and travel/accommodation/meeting expenses from Pfizer. Leone, M. declares personal fees from Gilead, MSD, Aspen, Ambu and Amomed. Lescure, F. X. declares personal fees (payment for lectures) from Gilead and MSD and travel/accommodation/meeting expenses from Astellas, Eumedica and MSD. Lim, W. S. declares his institution has received unrestricted investigator‐initiated research funding from Pfizer for an unrelated multicentre cohort study in which he is the Chief Investigator and research funding from the National Institute for Health Research, UK, for various clinical trials outside the submitted work. Liu, K. reports personal fees from MERA and receives a salary from TXP Medical completely outside the submitted work. Maier, Lars S. has nothing to declare with respect to the present work. Martin‐Blondel, G. declares support for attending meetings and personal fees from BMS, MSD, Janssen, Sanofi, Pfizer and Gilead for lectures outside the submitted work. Martin‐Loeches, I. declares lectures for Gilead, Thermofisher, Pfizer and MSD; advisory board participation for Fresenius Kabi, Advanz Pharma, Gilead, Accelerate and Merck; and consulting fees for Gilead outside of the submitted work. Martín‐Quiros, A. declares consulting fees for Gilead. Mentré, F. declares consulting fees from IPSEN, Servier and Da Volterra and reports research grants to her group from Sanofi, Roche, Servier and Da Voleterra, all outside the submitted work. Montrucchio, G. declares personal fees for lecture from Pfizer and Gilead outside the submitted work. Murthy, S. declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research. Nichol, A. declares a grant from the Health Research Board of Ireland to support data collection in Ireland (CTN‐2014‐012), an unrestricted grant from BAXTER for the TAME trial kidney substudy and consultancy fees paid to his institution from AM‐PHARMA. Nseir, S. declares lectures for Gilead, Pfizer, MSD, Biomérieux, Fisher & Paykel and Bio Rad, outside the submitted work. Openshaw, P. has served on scientific advisory boards for Janssen/J&J, Oxford Immunotech Ltd, GSK, Nestle and Pfizer (fees to Imperial College). He is Imperial College lead investigator on EMINENT, a consortium funded by the MRC and GSK. He is a member of the RSV Consortium in Europe (RESCEU) and Inno4Vac, Innovative Medicines Initiatives (IMI) from the European Union. Peltan, I. D. declares grant support from the National Institutes of Health and, outside the submitted work, grant support from Centers for Disease Control and Prevention, National Institutes of Health, and Jannsen and payments to his institution from Regeneron and Asahi Kasei Pharma. Pesenti, A. declares personal fees from Maquet, Novalung/Xenios, Baxter and Boehringer Ingelheim. Peytavin, G. declares consulting fees (for lectures and/or participation in advisory boards) and travel grants from Gilead Sciences, Janssen, Merck, Takeda, Theratechnologies and ViiV Healthcare. Poissy, J. declares personal fees from Gilead for lectures, outside the submitting work. Povoa, P. declares personal fees (for lectures and advisory boards) from MSD, Technophage, Sanofi and Gilead. Póvoas, D. declares consulting fees (for lectures and/or participation in advisory boards) from Roche and ViiV Healthcare and travel/accommodation/meeting expenses from Abbvie, Gilead Sciences, Janssen Cilag, Merck Sharp & Dohme and ViiV Healthcare. Rewa, O. declares honoraria from Baxter Healthcare Inc and Leading Biosciences Inc. Rossanese, A. declares consulting fees (for lectures and/or participation to advisory boards) from Emergent BioSolutions and Sanofi Pasteur, but all outside of the frame of the submitted work. Săndulescu, O. has been an investigator in COVID‐19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, Celltrion, Inc. and Atriva Therapeutics, outside the scope of the submitted work. Semple, M. G. reports grants from DHSC National Institute of Health Research UK, from the Medical Research Council UK and from the Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, supporting the conduct of the study; other interest in Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work. Serpa Neto, A. declares personal lecture fees from Drager outside the submitted work. Serrano‐Balazote, P. declares funding via his institution from Novartis and Janssen and personal fees or participation in advisory boards or participation to the speaker's bureau of Roche, all outside of the submitted work. Shrapnel, S. participated as an investigator for an observational study analysing ICU patients with COVID‐19 (for the Critical Care Consortium including ECMOCARD) funded by The Prince Charles Hospital Foundation during the conduct of this study. Streinu‐Cercel, Anca has been an investigator in COVID‐19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, Celltrion, Inc. and Atriva Therapeutics, outside the scope of the submitted work. Summers, C. reports that she has received fees for consultancy for Abbvie and Roche relating to COVID‐19 therapeutics. She was also the UK Chief Investigator of a GlaxoSmithKline plc sponsored study of a therapy for COVID and is a member of the UK COVID Therapeutic Advisory Panel (UK‐CTAP). Outside the scope of this work, Dr Summers' institution receives research grants from the Wellcome Trust, UKRI/MRC, National Institute for Health Research (NIHR), GlaxoSmithKline and AstraZeneca to support research in her laboratory. Susanne Dudman reports grants from Research Council of Norway Grant No. 312780. Tedder, R. reports grants from MRC/UKRI during the conduct of the study. In addition, R. Tedder has a patent United Kingdom Patent Application No. 2014047.1 ‘SARS‐CoV‐2 antibody detection assay’ issued. Terzi, N. reports personal fees from Pfizer, outside the submitted work. Timsit, J. F. participated in an advisory board for MSD, Pfizer, nabriva, Gilead, Shionoghi and Medimune outside the submitted work and declared lecture fees from MSD, Biomerieux, Pfizer and Shionoghi. Turtle, L. reports grants from MRC/UKRI during the conduct of the study and fees from Eisai for delivering a lecture related to COVID‐19 and cancer, paid to the University of Liverpool. Ullrich, R. reports grant funding to his institution from Apeptico, APEIRON, Biotest, Bayer, CCORE and Philips, as well as personal fees from Biotest. He holds European patent EP15189777.4 ‘Blood purification device’ and equity in CCORE Technology GesmbH, a medical device research and development company. Visseaux, B. declares personal fees from BioMérieux, Qiagen and Gilead and research grants from Qiagen, all outside the submitted work. West, E. reports grant funding from the Firland Foundation, the US‐CDC and the Bill and Melinda Gates Foundation for studies of COVID‐19 and grant funding from the US NIH for studies of other respiratory infections. Søraas, A. is a founder of the company Age Labs, which develops epigenetic tests including for COVID‐19 severity.