Expression of SARS-CoV-2 Receptor ACE2 Higher in Type-2-Low Asthma Patients

By Anne Harding

June 18, 2020

NEW YORK (Reuters Health) - Type-2-low asthmatics have higher expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium, as well as characteristics associated with increased risk of severe COVID-19, according to new findings.

The findings suggest that these patients may be at especially high risk of contracting COVID-19, and developing severe disease if they do become infected, Dr. Sally Wenzel, director of the Asthma and Environmental Lung Health Institute at the University of Pittsburgh Medical Center (UPMC), told Reuters Health by phone.

"They should not be putting themselves into high-risk situations, they should be continuing to work at home as much as they can," Dr. Wenzel said. "We would certainly want them to have their asthma under the best possible control."

The question of whether asthma increases the risk of severe COVID-19, or might even be protective, is controversial, she noted. "One of the reasons for that uncertainty is that asthma is a very heterogenous disease, and there are very likely to be subgroups of people with asthma that are high risk."

Dr. Wenzel and her team studied two large cohorts of asthma patients with stable disease to investigate whether ACE2 expression was associated with immune polarization.

Low absolute blood eosinophil count, a marker of Type 2 inflammation, was associated with increased ACE2 expression in bronchial epithelial cells (BEC), they found. ACE2 expression also correlated with expression of genes upregulated in viral infections, the team reports in the Journal of Allergy and Clinical Immunology.

When patients were clustered into four groups based on BEC gene expression, the authors found that levels of blood eosinophils varied with ACE2 expression. Patient cluster 1 (PC1), which had the highest mean Type-1-gene expression score, also had the highest level of ACE2 transcripts and the lowest mean Type-2-gene expression.

PC1 was all male, with higher mean resting diastolic pressure and a trend toward a greater likelihood of having been diagnosed with hypertension. Patients in this group also had a higher neutrophil-to-lymphocyte ratio and lower absolute levels of lymphocytes and eosinophils, characteristics also associated with COVID-19. They also had elevated lymphocytes in bronchoalveolar lavage (BAL).

"One of the surprising things from the findings was that we were able to so clearly link what was going on with the epithelial lining in the lung with the signature in the peripheral blood," Dr. Matthew J. Camiolo, a clinical instructor at UPMC and the study's lead author, told Reuters Health by phone. "It may give us some insight into things we can test for in the blood."

He added: "This is very much a pilot study, and there will have to be confirmatory work to give us a sense of what's going on at the protein level."

Allergist Dr. Brian Modena of National Jewish Health in Denver told Reuters Health, "This is an important study to highlight how heterogeneous asthmatic responses to COVID might be."

The fact that the study looked at gene expression at one point in time is limiting, he added.

"The gene expression is a marker, but it doesn't indicate the actual protein levels. That's one assumption that's not quite connected yet," Dr. Modena said by phone. "The other assumption is that having higher levels of ACE2 translates to a worse COVID infection, and that's not necessarily proven by any means."

SOURCE: Journal of Allergy and Clinical Immunology, online June 10, 2020.