Viral respiratory infections are the most common trigger of severe asthma
exacerbations in children and adults. Unexpectedly, large epidemiological studies of the
COVID-19 pandemic in China did not identify asthma as a risk factor of severe COVID19 related illnesses.(2) Here, we report that respiratory allergy and controlled allergen
exposures are each associated with significant reductions in ACE2 expression. ACE2
expression was lowest in those with both high levels of allergic sensitization and
asthma. Importantly, non-atopic asthma was not associated with reduced ACE2
expression. Given that ACE2 serves as the receptor for SARS-CoV-2, our findings
suggest a potential mechanism of reduced COVID-19 severity in patients with
respiratory allergies. However, it is likely that additional factors beyond ACE2
expression modulate the response to COVID-19 in allergic individuals, and elucidation
of these factors may also provide important insights into COVID-19 disease
pathogenesis.
Strengths of our study include carefully phenotyped cohorts of children and
adults. Further, the allergen challenge studies included both upper and lower airway
samples, with each demonstrating a consistent impact on ACE2 expression. Limitations
include lack of clinical information to directly link ACE2 expression to SARS-CoV-2
infection and illness severity in our study populations. In addition, we do not have data
on the ACE2 protein levels to confirm the gene expression data, though previous work
suggests a direct association between ACE2 mRNA levels and ACE2 protein levels in
the lung.(8)
