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

Background Mortality rates of UK patients hospitalised with COVID-19 appeared to fall during the first wave. We quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. Methods The International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK recruited a prospective cohort admitted to 247 acute UK hospitals with COVID-19 in the first wave (March to August 2020). Outcome was hospital mortality within 28 days of admission. We performed a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and hospital mortality adjusting for confounders (demographics, comorbidity, illness severity) and quantifying potential mediators (respiratory support and steroids). Findings Unadjusted hospital mortality fell from 32.3% (95%CI 31.8, 32.7) in March/April to 16.4% (95%CI 15.0, 17.8) in June/July 2020. Reductions were seen in all ages, ethnicities, both sexes, and in comorbid and non-comorbid patients. After adjustment, there was a 19% reduction in the odds of mortality per 4 week period (OR 0.81, 95%CI 0.79, 0.83). 15.2% of this reduction was explained by greater disease severity and comorbidity earlier in the epidemic. The use of respiratory support changed with greater use of non-invasive ventilation (NIV). 22.2% (OR 0.94, 95%CI 0.94, 0.96) of the reduction in mortality was mediated by changes in respiratory support. Interpretation The fall in hospital mortality in COVID-19 patients during the first wave in the UK was partly accounted for by changes in case mix and illness severity. A significant reduction was associated with differences in respiratory support and critical care use, which may partly reflect improved clinical decision making. The remaining improvement in mortality is not explained by these factors, and may relate to community behaviour on inoculum dose and hospital capacity strain. Funding NIHR & MRC Key points / Research in Context Evidence before this study Risk factors for mortality in patients hospitalised with COVID-19 have been established. However there is little literature regarding how mortality is changing over time, and potential explanations for why this might be. Understanding changes in mortality rates over time will help policy makers identify evolving risk, strategies to manage this and broader decisions about public health interventions. Added value of this study Mortality in hospitalised patients at the beginning of the first wave was extremely high. Patients who were admitted to hospital in March and early April were significantly more unwell at presentation than patients who were admitted in later months. Mortality fell in all ages, ethnic groups, both sexes and in patients with and without comorbidity, over and above contributions from falling illness severity. After adjustment for these variables, a fifth of the fall in mortality was explained by changes in the use of respiratory support and steroid treatment, along with associated changes in clinical decision-making relating to supportive interventions. However, mortality was persistently high in patients who required invasive mechanical ventilation, and in those patients who received non-invasive ventilation outside of critical care. Implications of all the available evidence The observed reduction in hospital mortality was greater than expected based on the changes seen in both case mix and illness severity. Some of this fall can be explained by changes in respiratory care, including clinical learning. In addition, introduction of community policies including wearing of masks, social distancing, shielding of vulnerable patients and the UK lockdown potentially resulted in people being exposed to less virus. The decrease in mortality varied depending on the level of respiratory support received. Patients receiving invasive mechanical ventilation have persistently high mortality rates, albeit with a changing case-mix, and further research should target this group. Severe COVID-19 disease has primarily affected older people in the UK. Many of these people, but not all have significant frailty. It is essential to ensure that patients and their families remain at the centre of decision-making, and we continue with an individualised approach to their treatment and care