Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Early descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>We identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 – 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 – 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 – 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>These results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>This work was supported by the Medical Research Council MR/V015737/1.</jats:p></jats:sec>