Reply to “Does asthma affect outcomes of patients with COVID-19 infections?”

To the Editor:

We would like to thank Kalemci et al¹ for highlighting our paper published in the August issue of the Journal of Allergy and Clinical Immunology: In Practice.² The impact of COVID-19 on patients with asthma and their COVID-19 outcome has been a matter of several investigations in the past few months. As the authors mentioned, asthma is a heterogenic disease with several endotypes, which may respond to infectious processes differently. Our results are in agreement with other papers that were published in the following month showing that asthma does not decrease or increase hospitalization rate and length for COVID-19.³ Additional studies showed that atopy might play an important role in the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our follow-up large 2-center study has also shown that atopy is a potential protective factor and a positive prognostic factor for decreased severity of COVID-19.⁴ Furthermore, we have found that, among different endotypes of asthma, only nonallergic asthma was associated with prolonged need for intubation,⁴ which agrees with a recent comprehensive large study.⁵ This study showed that nonallergic asthma was associated with a higher risk of severe COVID-19.⁵ This is also consistent with translational studies. Although gene expressions of 2 key mediators for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), have been shown to be different in allergic individuals, potentially protecting them from severe illness, in a large study in which all patients with asthma were combined together, the expression of both genes was similar between patients with asthma and healthy subjects.⁶ This indicates that asthma in general is not a risk factor for more or less severe COVID-19 illness. However, as a chronic lung disease prone to viral-induced exacerbation, this might place those with severe COVID-19 at risk for a longer duration of pulmonary inflammation.^{2 , 5} Furthermore, an allergic background and differential expression of ACE2 and TMPRSS2 may dampen the strong inflammatory response to SARS-CoV-2 in patients with allergic asthma, leading to the lack of increased severity reported in patients with nonallergic asthma.^{2 , 4 , 5}

Another important factor that needs to be considered and further investigated is the impact of racial differences on COVID-19 outcome in patients with asthma. The studies that did not find any difference in terms of COVID-19 severity or intubation time in patients with asthma were performed in predominantly non–African American (AA) populations, such as from China, or study populations with only 21% to 26% AAs.³ In our series from the city of Chicago, 59% of COVID-19 patients with asthma were AA.² Interestingly, Peters et al⁶ have demonstrated that, among patients with asthma, AA race was associated with higher expression of ACE2 and TMPRSS2. Consistent with that study, our as yet unpublished follow-up study has shown that AAs with asthma and COVID-19 infection had a significantly higher rate of asthma exacerbation and longer duration of asthma symptoms after COVID-19 compared with their white counterparts. Specifically, 68% of AAs versus 35% of whites (P = .032) report symptoms suggestive of asthma exacerbation after COVID, and mean ± standard deviation durations of asthma exacerbation symptoms were 3.6 ± 2.1 weeks versus 1.5 ± 1.3 weeks in AAs and whites, respectively (P = .045). We have also demonstrated that, although asthma is not a risk factor for COVID-19 hospitalization in any age group, AA children are at a significantly higher risk for COVID-19 adverse outcomes.⁷ Multiple inter-related variables, such as uncontrolled comorbidities, reduced access to health care, and other socioeconomic factors, and possibly a genetic predisposition can impact these important results and need to be further investigated.

Kalemci et al¹ also bring up another important concept about the use of inhaled corticosteroids (ICS) for asthma therapy and risk of COVID-19 severity. Based on the impact of ICS on decreasing the expression of ACE2 expression, it was hypothesized that the use of ICS in asthmatics might decrease COVID-19 severity.⁶ However, in a large study, Chhiba et al³ reported that ICS did not increase or decrease the risk of COVID-19 hospitalization in patients with asthma after adjusting for multiple potential confounding factors.