Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

ISARIC4C Investigators

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Background Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital.

Methods In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260.

Findings Between March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32.3% (95% CI 31.8-32.7) in March 9 to April 26, 2020, to 16.4% (15.0-17.8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0.68 [95% CI 0.65-0.71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10.2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22.2%, OR 0.95 (0.94-0.95) of the reduction in in-hospital mortality.

Interpretation The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Original languageEnglish
Pages (from-to)773-785
Number of pages13
JournalThe Lancet Respiratory Medicine
Issue number7
Publication statusPublished - Jul 2021

Bibliographical note

Funding Information:
ABD reports grants from Department of Health and Social Care (DHSC), during the conduct of the study; and grants from Wellcome Trust, outside of the submitted work. LT reports grants from Wellcome Trust. JSNV-T reports salary support from DHSC, during the conduct of the study, and is seconded to DHSC. PJMO reports personal fees from consultancies and from the European Respiratory Society; grants from the Medical Research Council (MRC), MRC Global Challenge Research Fund, EU, NIHR BRC, MRC/GSK, Wellcome Trust, NIHR (Health Protection Research Unit [HPRU] in Respiratory Infection); and is an NIHR senior investigator outside of the submitted work; his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the Society. JKB reports grants from MRC UK. MGS reports grants from DHSC NIHR UK, MRC UK, and HPRU in Emerging and Zoonotic Infections, University of Liverpool during the conduct of the study; and other from Integrum Scientific (Greensboro, NC, USA) outside of the submitted work. RHM reports grants from BREATHE, the health data research hub for respiratory health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and is delivered by Health Data Research UK. All other authors declare no competing interests.

Funding Information:
This work is supported by grants from the NIHR (award CO-CIN-01); the MRC (grant MC_PC_19059); the NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907); the NIHR HPRU in Respiratory Infections at Imperial College London with Public Health England (award 200927); the Wellcome Trust and Department for International Development (215091/Z/18/Z); the Bill & Melinda Gates Foundation (OPP1209135); the Liverpool Experimental Cancer Medicine Centre (C18616/A25153); the NIHR Biomedical Research Centre at Imperial College London (IS-BRC-1215–20013); the EU Platform for European Preparedness Against (Re-) emerging Epidemics (FP7 project 602525); and the NIHR Clinical Research Network, which provided infrastructure support for this research. PJMO is supported by an NIHR Senior Investigator Award (201385). JSNV-T is seconded to the Department of Health and Social Care, England. ABD acknowledges funding from the Wellcome Trust (216606/Z/19/Z); SF from the Wellcome Trust (210758/Z/18/Z); KD-O from the Wellcome Trust for the Royal Society Sir Henry Dale Fellowship (218554/Z/19/Z); RHK from UKRI (MR/S017968/1); DDA from the MRC (MCUU 00002/11); BDMT from the MRC (MC_UU_00002/2); and LT from the Wellcome Trust (205228/Z/16/Z). This work uses data provided by patients and collected by the NHS as part of their care. We are extremely grateful to the 2648 front-line NHS clinical and research staff and volunteer medical students, who collected these data under challenging circumstances; and the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar (Wellcome Trust) and Nahoko Shindo (WHO). The views expressed in this Article are those of the authors and do not necessarily reflect those of the DHSC, Department of International Development, NIHR, MRC, Wellcome Trust or Public Health England.

Publisher Copyright:
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license


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