A lab study identifies the mechanism used by budesonide to protect against COVID-19.

Key Messages

The SARS-CoV-2 virus causes COVID-19 by using a cell surface receptor protein (ACE2) as an entry route into the lungs. Increased levels of ACE2 make individuals more vulnerable to COVID-19's adverse effects.

This lab study examined the effect of inhaled corticosteroids (ICS) on the levels of the ACE2 receptor, which may help reduce the vulnerability of patients to SARS-CoV-2 infection.

In particular, the study tested cells from patients with chronic obstructive pulmonary disease (COPD) and measured the effect of budesonide on the levels of the problematic ACE2 receptor.

Results revealed that inhalable steroids, including budesonide, lowered the levels of ACE2 in mouse models and in mucous excretions of COPD patients.

This study suggests that reducing ACE2 levels by treating with budesonide may reduce the likelihood of patients infected with SARS-CoV-2 developing COVID-19.

Publication Date: October 14, 2020
Peer Reviewed: Yes
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.1016/j.jaci.2020.09.034

Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon


The mechanisms underlying altered susceptibility and propensity to severe Coronavirus disease 2019 (COVID-19) disease in at-risk groups such as patients with chronic obstructive pulmonary disease (COPD) are poorly understood. Inhaled corticosteroids (ICSs) are widely used in COPD, but the extent to which these therapies protect or expose patients to risk of severe COVID-19 is unknown.

The aim of this study was to evaluate the effect of ICSs following pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme-2 (ACE2).

We evaluated the effect of ICS administration on pulmonary ACE2 expression in vitro in human airway epithelial cell cultures and in vivo in mouse models of ICS administration. Mice deficient in the type I IFN-α/β receptor (Ifnar1−/−) and administration of exogenous IFN-β were used to study the functional role of type-I interferon signaling in ACE2 expression. We compared sputum ACE2 expression in patients with COPD stratified according to use or nonuse of ICS.

ICS administration attenuated ACE2 expression in mice, an effect that was reversed by exogenous IFN-β administration, and Ifnar1−/− mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect. ICS administration attenuated expression of ACE2 in airway epithelial cell cultures from patients with COPD and in mice with elastase-induced COPD-like changes. Compared with ICS nonusers, patients with COPD who were taking ICSs also had reduced sputum expression of ACE2.

ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2. This effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.