Abstract
Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.
Footnotes
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Conflict of interest: Luis Felipe Reyes
Conflict of interest: Murthy, S declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research.
Conflict of interest: Esteban Garcia-Gallo
Conflict of interest: Mike Irvine
Conflict of interest: Laura Merson
Conflict of interest: Martin-Loeches I. declares consulting fees for Gilead outside of the submitted work.
Conflict of interest: Jordi Rello
Conflict of interest: Fabio S. Taccone
Conflict of interest: Robert A. Fowler
Conflict of interest: Annemarie B. Docherty
Conflict of interest: Christiana Kartsonaki
Conflict of interest: Irene Aragao
Conflict of interest: Peter W. Barrett
Conflict of interest: Abigail Beane
Conflict of interest: Aidan Burrell
Conflict of interest: Matthew Pellan Cheng
Conflict of interest: Michael D. Christian
Conflict of interest: Jose Pedro Cidade
Conflict of interest: Barbara Wanjiru Citarella
Conflict of interest: Christl A. Donnelly
Conflict of interest: Susana Fernandes
Conflict of interest: Craig French
Conflict of interest: Rashan Haniffa
Conflict of interest: Ewen M. Harrison
Conflict of interest: 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.
Conflict of interest: Mark Joseph
Conflict of interest: Irfan Khan
Conflict of interest: Michelle E. Kho
Conflict of interest: Anders Benjamin Kildal
Conflict of interest: Kutsogiannis, D.J. declares personal fees for a lecture from Tabuk Pharmaceuticals and the Saudi Critical Care Society.
Conflict of interest: François Lamontagne
Conflict of interest: Lee, T.C. declares research salary support from les Fonds de recherche du Québec – Santé.
Conflict of interest: Gianluigi Li Bassi
Conflict of interest: Jose Wagner Lopez Revilla
Conflict of interest: Catherine Marquis
Conflict of interest: Jonathan Millar
Conflict of interest: Raul Neto
Conflict of interest: Nichol, A. declares a grant from the Health Research Board of Ireland to support data collection in Ireland (CTN-2014-012).
Conflict of interest: Rachael Parke
Conflict of interest: Rui Pereira
Conflict of interest: Sergio Poli
Conflict of interest: Povoa, P. declares personal fees (for lectures and advisory boards) from MSD, Technophage, Sanofi, and Gilead.
Conflict of interest: Kollengode Ramanathan
Conflict of interest: Rewa, O. declares consulting fees from Baxter Inc.
Conflict of interest: Jordi Riera
Conflict of interest: 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. S. Shrapnel reports in kind support from the Australian Research Council Centre of Excellence for Engineered Quantum Systems (CE170100009).
Conflict of interest: Maria Joao Silva
Conflict of interest: Andrew Udy
Conflict of interest: Timothy Uyeki
Conflict of interest: Steve A. Webb
Conflict of interest: Evert-Jan Wils
Conflict of interest: Amanda Rojek
Conflict of interest: Piero L. Olliaro
Conflict of interest: Allavena, C. declares personal fees from ViiVHealthcare, MSD, Janssen and Gilead, all outside the submitted work.
Conflict of interest: Andréjak, C. declares personal fees for lecture from Astra Zeneca, outside the submitted work.
Conflict of interest: Cheng, M. declares grants from McGill Interdisciplinary Initiative in Infection and Immunity, grants from Canadian Institutes of Health Research, during the conduct of the study; personal fees from GEn1E Lifesciences (as a member of the scientific advisory board), 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, M. Cheng 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.
Conflict of interest: Cholley, B. declares personal fees (for lectures and participation to advisory boards) from Edwards, Amomed, Nordic Pharma, and Orion Pharma.
Conflict of interest: 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.
Conflict of interest: Dalton, H. declares personal fees for medical director of Innovative ECMO Conceots and honorarium from Abiomed/BREETHE Oxi-1 and Instrumentation Labs.
Conflict of interest: Dyrhol-Riise, AM. declares grants from Gilead outside this work.
Conflict of interest: Deplanque, D. declares personal fees from Biocodex, Bristol-Myers Squibb and Pfizer (advisory boards).
Conflict of interest: Dudman, S. reports grants from Research Council of Norway grant no 312780.
Conflict of interest: Durante-Mangoni, E. declares funding via his Institution from MSD, 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.
Conflict of interest: Grasselli, G. declares personal fees from Getinge, Biotest, Draeger Medical, Fisher & Paykel, MSD and unrestricted research grant from MSD and Fisher & Paykel, all outside the submitted work.
Conflict of interest: Guerguerian, AM. 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.
Conflict of interest: 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.
Conflict of interest: 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.
Conflict of interest: Kimmoun, A. declares personal fees (payment for lectures) from Baxter, Aguettant, Aspen.
Conflict of interest: Kumar, D. declares grants and personal fees from Roche, GSK and Merck; and personal fees from Pfizer and Sanofi.
Conflict of interest: Kutsogiannis, D.J. declares personal fees for a lecture from Tabuk Pharmaceuticals and the Saudi Critical Care Society.
Conflict of interest: Laffey, J. reports that he has received fees for consultancy from GlaxoSmithKline and from Baxter Therapeutics for work outside the scope of this work.
Conflict of interest: Lee, J. reports grants from European Commission PREPARE grant agreement No 602525, European Commission RECOVER Grant Agreement No 101003589 and European Commission ECRAID-Plan Grant Agreement 825715 supporting the conduct, coordination and management of the work.
Conflict of interest: Lee, T.C. declares research salary support from les Fonds de recherche du Québec – Santé.
Conflict of interest: Lefèvre, B. declares travel/accommodation/meeting expenses from Mylan and Gilead, all outside the submitted work.
Conflict of interest: Lemaignen, A. declares personal fees (payment for lectures) from MSD and Gilead; and travel/accommodation/meeting expenses from Pfizer.
Conflict of interest: Lescure, F.X. declares personal fees (payment for lectures) from Gilead, MSD; and travel/accommodation/meeting expenses from Astellas, Eumedica, MSD.
Conflict of interest: Liu, K. reports personal fees from MERA and receives a salary from TXP Medical completely outside the submitted work.
Conflict of interest: Martin-Loeches I. declares consulting fees for Gilead outside of the submitted work.
Conflict of interest: 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.
Conflict of interest: Murthy, S declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research.
Conflict of interest: Nichol, A. declares a grant from the Health Research Board of Ireland to support data collection in Ireland (CTN-2014-012).
Conflict of interest: 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.
Conflict of interest: 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, and Jannsen and payments to his institution for trials by Regeneron and Asahi Kasei Pharma on which he served as an investigator.
Conflict of interest: Pesenti, A. declares personal fees from Maquet, Novalung/Xenios, Baxter, and Boehringer Ingelheim.
Conflict of interest: Poissy, J. declares personal fees from Gilead for lectures, outside the submitting work.
Conflict of interest: Povoa, P. declares personal fees (for lectures and advisory boards) from MSD, Technophage, Sanofi, and Gilead.
Conflict of interest: 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.
Conflict of interest: Rewa, O. declares consulting fees from Baxter Inc.
Conflict of interest: 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.
Conflict of interest: Săndulescu, O. has been an investigator in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, and Celltrion, Inc., outside the scope of the submitted work.
Conflict of interest: 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.
Conflict of interest: Serpa Neto, A. declares personal lecture fees from Drager outside the submitted work.
Conflict of interest: 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. S. Shrapnel reports in kind support from the Australian Research Council Centre of Excellence for Engineered Quantum Systems (CE170100009).
Conflict of interest: Streinu-Cercel, Adrian has been an investigator in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, and Celltrion, Inc., outside the scope of the submitted work.
Conflict of interest: Streinu-Cercel, Anca has been an investigator in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, and Celltrion, Inc., outside the scope of the submitted work.
Conflict of interest: Summers, C. reports that she has received fees for consultancy for Abbvie 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.
Conflict of interest: 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.
Conflict of interest: Timsit, J.F. declares personal fees from Merck, Pfizer, Gilead, Beckton dickinson, Medimune, Bayer pharma, and reports research grants to his research unit from Pfizerpers, Merck, Thermofisher.
Conflict of interest: Troost, J. declares personal fees from General Electric and Procter and Gamble.
Conflict of interest: Turtle, L. reports fees from Eisai for delivering a lecture related to COVID-19 and cancer, paid to the University of Liverpool.
Conflict of interest: 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.
Conflict of interest: Visseaux, B. declares personal fees from BioMérieux, Qiagen and Gilead and research grants from Qiagen, all outside the submitted work.
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- Received September 23, 2021.
- Accepted November 10, 2021.
- Copyright ©The authors 2021
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