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

Abstract

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.

Funding: National Institute for Health Research and the Medical Research Council.

Figure 1

Hospital admissions and in-hospital mortality between March 9 and Aug 2, 2020 (A) Daily adult COVID-19 admissions by age. Cases are stacked by age group. (B) Weekly unadjusted mortality in adult inpatients admitted to hospital with COVID-19. Error bars represent 95% CIs, calculated by use of an exact method. Dashed lines indicate three equal time periods (weeks 11–17, 18–24, and 25–31).

Figure 2

Proportion of adults admitted to hospital with COVID-19 and inpatient mortality between March 9 and Aug 2, 2020, stratified by age (A), sex at birth (B), number of comorbidities (C), ethnic group (D), and deprivation quintile (E) In A–E, all plots on the left show the proportion of adults admitted to hospital with COVID-19 by patient characteristics, and all plots on the right show unadjusted in-hospital mortality rates during the time period. In all plots on the left, the proportions of participants are stacked by characteristic. In E, the deprivation quintile ranges from 1 (most deprived) to 5 (least deprived). Missing data are excluded from the figure. Shaded areas represent 95% CIs.

Figure 3

Proportion of adults admitted to hospital with COVID-19 and inpatient mortality between March 9 and Aug 2, 2020, stratified by respiratory rate (A), peripheral oxygen saturation on room air (B), Glasgow coma score (C), urea concentration (D), and C-reactive protein concentration (E) In A–E, all plots on the left show the proportion of adults admitted to hospital with COVID-19 by severity of illness at admission, and all plots on the right show the unadjusted in-hospital mortality rate each week during the time period. In all plots on the left, the proportions of participants are stacked by severity of illness at admission. Missing data are excluded from the figure.

Figure 4

OR for in-hospital mortality for week of admission per 7-week period In-hospital mortality unadjusted for week of admission (A); adjusted for age, sex, deprivation, and hospital (B); adjusted for age, sex, deprivation quintile, severity of illness (respiratory rate, oxygen saturations, Glasgow coma score, serum urea concentration, and C-reactive protein), and number of comorbidities (C); and adjusted for age, sex, deprivation quintile, severity of illness, number of comorbidities, and potential mediators (maximal level of care, respiratory support, and treatment with steroids). Error bars represent 95% CIs. OR=odds ratio.

Figure 5

Causal graph with natural effects models mediation analysis The OR for the total natural indirect effect was 0·95 (95% CI 0·94–0·95, p<0·0001; percentage of effect through indirect path 22·2%; joint mediators) and for the pure natural direct effect was 0·84 (0·82–0·87, p<0·0001; percentage of effect from direct path 77·8%). IMD=index of multiple deprivation. YXM and YM=unmeasured confounders. OR=odds ratio. *Arrows from steroid treatment mediator confounders are not shown for clarity.