Inhaled Corticosteroids and COVID-19.

To the Editor:

Maes and colleagues (1) present data from lung tissue that showed that mRNA expression for ACE2 (angiotensin-converting enzyme 2) was significantly greater in 38 patients with moderate chronic obstructive pulmonary disease (COPD) compared with 61 healthy control subjects but not compared with a group of 7 patients with asthma or asthma–COPD overlap syndrome. Furthermore, values for ACE2 expression in a heterogeneous group of 23 patients with obstructive airway disease (OAD) comprising COPD, asthma–COPD overlap syndrome, or asthma not receiving inhaled corticosteroids (ICS) were significantly higher than values in 56 control subjects but not values in 25 patients with OAD receiving ICS.

The problem with interpreting these results in a heterogeneous group of patients with OAD is that ACE2 is upregulated in smokers and in those with COPD but is downregulated in those with asthma and those with atopy (2, 3). Furthermore, assaying ACE2 mRNA only tells one-half of the story with regard to entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into lung tissue, as asthma and atopy are both associated with upregulation of TMPRSS2 (transmembrane protease serine 2) in airway epithelial cells (3). In this regard, in induced sputum cells from asthma patients, ICS have been shown to exhibit suppressive effects ex vivo on both ACE2 and TMPRSS2 expression (4).

Maes and colleagues (1) fail to point out the inhibitory in vitro effects of ICS on local and systemic production of IL-6 (5, 6), this being the strongest predictor for impending respiratory failure in severe coronavirus disease (COVID-19) (7). Finally, a more specific suppressive effect from ICS on SARS-CoV-2 replication has been described with ciclesonide and mometasone furoate but not with budesonide, beclomethasone, or fluticasone (8).

We believe that, taken together, these observations reinforce the need for patients with eosinophilic asthma and COPD to continue receiving their controller therapy containing ICS, as that will provide optimal disease control and perhaps also confer protection against viral triggers, perhaps including SARS-CoV-2.