Respiratory allergy, asthma and controlled allergen exposure were associated with significantly reduced gene expression in a protein that the coronavirus uses to infect cells with COVID-19, according to a new study by the University of Wisconsin School of Medicine and Public Health.

The study, published online April 22 in the Journal of Allergy and Clinical Immunology, suggests a possible reason why people with respiratory allergy and asthma do not seem to experience some of the more severe and life-threatening manifestations of the COVID-19 disease. Importantly, previous studies have shown that higher expression of ACE2 is associated with smoking, diabetes, and hypertension — all of which are known risk factors for COVID-19 disease severity.

Dan Jackson
Daniel Jackson

Viral respiratory infections are the most common trigger of severe asthma exacerbations in children and adults, and it was widely assumed that the novel coronavirus would be no different. Unexpectedly, reports out of China found that asthma and respiratory allergies were not significant risk factors for severe COVID-19 illness in that country. As a result, UW researchers hypothesized that reduced ACE2 gene expression might be one of the contributing reasons why.

“We were surprised to learn that the COVID-19 pandemic in China did not seem to impact people with asthma as severely as we would’ve expected it to,” said Daniel Jackson, MD, lead investigator and associate professor of pediatrics and medicine at UW School of Medicine and Public Health. “Knowing that other risk factors for severe COVID-19 illness like hypertension and obesity lead to increased ACE2 expression, we wanted to determine if patients with allergies and asthma could have reduced ACE2 gene expression as a potential explanation for this unexpected early finding from the outbreak.”

Researchers used data from three different cohorts of children and adults to determine whether asthma and respiratory allergy are associated with reduced ACE2 expression in airway cells. In all three studies, total RNA was extracted from nasal or lower airway samples. Within the cohort of children (n=318), moderate and high levels of allergy were associated with progressively greater reductions in ACE2 expression. Children with high levels of allergy and asthma had the lowest ACE2 expression. In the adult cohorts (n=47), allergen exposure led to significant reductions in ACE2 expression as well.

Researchers say, however, that it is likely that additional factors beyond ACE2 expression modulate the response to COVID-19 in allergic individuals, and additional research that examines those factors may also provide important insights into COVID-19 disease pathogenesis. Future studies focused on respiratory allergy, asthma and, perhaps, other allergic disorders are needed to provide greater understanding of the impact of underlying allergy on COVID-19 susceptibility and disease severity, and further examination of these relationships could identify novel therapeutic strategies to more effectively control this pandemic.

Early data from the beginning of the pandemic in the U.S. are mixed with regard to asthma and risk for severe COVID-19 illness potentially because the reports have not specified whether asthma was allergic in nature or not, an important differentiation that relates to the study’s findings. Allergic asthma is the most common form of asthma, affecting 70–90 percent of asthmatic children and about 50 percent of asthmatic adults. Allergic asthmatics often have flares due to both respiratory viruses and allergens.

Funding for this study was provided by the National Institute of Allergy and Infectious Diseases (grant numbers UM1AI114271 and UM1AI109565) and the National Heart Lung and Blood Institute (grant number RO1HL12384), both part of the National Institutes of Health.

A copy of the study is available online at the Journal of Allergy and Clinical Immunology.