Risk of Hospitalized COVID-19 in COPD: Single-Inhaler Triple Versus Dual Bronchodilator Therapy

Our objective was to estimate the effect of initiating an inhaled corticosteroids-containing single-inhaler triple agent (ICS-LABA-LAMA) compared with a single-inhaler LABA-LAMA dual bronchodilator in patients with COPD on the risk of severe COVID-19 prior to the roll-out of vaccines.

We conducted a cohort study emulating a randomized trial, among patients with COPD aged 40 years or more in the UK, comparing those who initiated a triple inhaler with those who initiated a dual bronchodilator inhaler between March 1 and December 31, 2020. Weighting by fine stratification of the propensity score was used to account for confounders. The risk of hospitalized COVID-19 was compared with a Cox proportional hazards model in an as-treated analysis with a 30-day grace period.

The study cohort included 876 patients initiating a triple inhaler and 5010 initiating a dual LABA-LAMA inhaler. The adjusted incidence rate of hospitalized COVID-19 was 5.6 per 100 person-years in the triple inhaler group and 2.9 per 100 person-years in the dual inhaler group, with a corresponding hazard ratio (HR) of 1.96 (95% confidence interval 1.01-3.77). Sensitivity analyses on the duration of the grace period, using an intent-to-treat exposure classification, or starting follow-up 14 days after treatment initiation (accounting for treatment initiation for an undocumented SARS-CoV-2 infection) were generally consistent with the main analysis.

Patients with COPD prescribed an ICS-containing triple inhaler were potentially exposed to an increased risk of severe COVID-19 prior to the vaccine era. As SARS-CoV-2 continues to cause significant burden, these findings should be considered when determining initiation of inhaled treatment in COPD.