• Annemarie B Docherty, Rachel H Mulholland, Nazir I Lone, Christopher P Cheyne, Daniela De Angelis, Karla Diaz-Ordaz, Cara Donegan, Thomas M Drake, Jake Dunning, Sebastian Funk, Marta García-Fiñana, Michelle Girvan, Hayley E Hardwick, Janet Harrison, Antonia Ho, David M Hughes, Ruth H Keogh, Peter D Kirwan, Gary Leeming, Nguyen Van-TamJonathan SJSDivision of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK., Riinu Pius, Clark D Russell, Rebecca G Spencer, Brian Dm Tom, Lance Turtle, Peter Jm Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, and ISARIC4C Investigators.
• Centre for Medical Informatics, University of Edinburgh, Edinburgh, UK. Electronic address: annemarie.docherty@ed.ac.uk.
• Lancet Respir Med. 2021 Jul 1; 9 (7): 773-785.

BackgroundMortality 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.MethodsIn 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.FindingsBetween 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.InterpretationThe 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.FundingNational Institute for Health Research and the Medical Research Council.Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

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