Association of Respiratory Allergy, Asthma, and Expression of the SARS-CoV-2 …

Jackson DJ, Busse WW, Bacharier LB, et al. Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2. J Allergy Clin Immunol. 2020;146(1):203-206.e3. doi:10.1016/j.jaci.2020.04.009

The novel coronavirus SARS-CoV-2 (COVID-19) was recognized in December 2019 as a cause of severe pneumonia and has now led to a global pandemic.1 Respiratory illnesses caused by COVID-19 cover a range of severity. The identification of risk and protective factors for disease severity from COVID-19 is critical to direct development of new treatments and infection prevention strategies. Early large case series have identified a number of risk factors for severe disease, including older age, hypertension, diabetes, cardiovascular disease, tobacco exposure, and chronic obstructive pulmonary disease.2 The US Centers for Disease Control and Prevention lists asthma as a risk factor for severe COVID-19 illness, which is logical given that many respiratory viruses have been well established to cause more serious illnesses in those with chronic airway diseases such as asthma. However, asthma and respiratory allergy have not been identified as significant risk factors for severe COVID-19 illness in case series from China.2 These preliminary reports led us to question whether we could identify features of allergy and/or asthma that could be associated with potential for reduced severity of COVID-19 illness.

SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as its cellular receptor, as do SARS-CoV and the coronavirus NL63.1 Higher ACE2 expression increases in vitro susceptibility to SARS-CoV,3 and studies examining factors that affect ACE2 gene expression have revealed that its upregulation is associated with smoking, diabetes, and hypertension, all of which are associated with increased severity of COVID-19 illness

We hypothesized that 1 potential explanation for the unexpected observation that asthma and other allergic diseases may not be a risk factor for severe COVID-19 disease is a reduced ACE2 gene expression in airway cells and thus decreased susceptibility to infection. To test this hypothesis, we examined whether asthma and respiratory allergy are associated with reduced ACE2 expression in airway cells from 3 different cohorts of children and adults. In all 3 studies, total RNA was extracted from nasal or lower airway epithelial brush samples, with RNA sequencing performed independently for each study as previously described and provided in detail in the Supplementary Information (available in this article’s Online Repository at www.jacionline.org).5 Differential expression of ACE2 was assessed by using a weighted linear mixed effects model (limma) appropriate for RNA sequencing data and an empiric Bayes method.

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