Different effect of inhaled and systemic corticosteroids on the outcome of COVID-19 among patients with asthma.

To the Editor:

We read with great interest the study by Ren et al, which investigated the effect of allergic rhinitis (AR) and/or asthma on the risk of COVID-19 infection, severity, and mortality, and also assessed the impact of long-term AR and/or asthma medications on the outcomes of COVID-19. On the basis of the analysis of 770,557 adult participants who completed SARS-CoV-2 testing between March 16 and December 31, 2020, in the UK, they found that asthma would be a protective factor of SARS-CoV-2 infection among patients aged <65; however, asthma would be associated with a higher risk of COVID-19 hospitalization. However, we have serious concerns about several important residual confounding factors, which might influence the results of this study.

First, the authors assessed the effect of several long-term medications for AR or asthma, including antihistamine, β2-adrenoceptor agonists, and corticosteroid, but none of them showed association with COVID-19 infection or severity. A previous study showed that the recent use of systemic corticosteroid was significantly associated with increased risk of both moderate-to-severe COVID-19 and all-cause mortality. , In contrast, several randomized controlled trials demonstrated the positive impact of inhaled budesonide on the outcome of COVID-19 among patients with asthma. , Therefore, we wonder whether the effect of systemic and inhaled corticosteroids (ICS) could differ. However, we only see that the number of events was lower in the ICS users than those receiving systemic corticosteroids in Table E4. Further subgroup analysis according to the use of inhaled corticosteroids similar to the ones in Figure 2 is warranted to clarify this issue, and additional evaluation about a dose-response relationship is needed.

Second, the severity of asthma is another confounding factor affecting the outcome of COVID-19. One study using Swedish National Airway Register showed that patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, would be associated with an increased risk of severe COVID-19. Similar findings were demonstrated in another national incident cohort study in Scotland.

In conclusion, although Ren et al’s study provided useful information, further analysis according to the use of corticosteroid and the severity of asthma is needed.