COVID-19-related gene expression higher in specific asthma subgroups
Angiotensin-converting enzyme 2 and transmembrane protease serine 2 mediate SARS-COV-2 entry into host cells. Higher expression of ACE2 and TMPRSS2 in sputum cells of patients with asthma identified subgroups at risk of COVID-19 morbidity.
“We found that among patients with asthma, gene expression of ACE2 and TMPRSS2 was higher in patients of male sex, Black race and patients with a history of diabetes mellitus,” Michael C. Peters, MD, assistant professor of medicine in the division of pulmonary and critical care medicine at the University of California, San Francisco, told Healio.
Researchers analyzed gene expression for ACE2, TMPRSS2 and intercellular adhesion molecule 1 (ICAM-1), the major intercellular protein that mediates entry of human rhinoviruses, in sputum cells of 330 participants (mean age, 48.5 years; 69% female; 66% white) in the Severe Asthma Research Program-3 and in 79 healthy control participants (mean age, 40.6 years; 66% female; 57% white). Participants inhaled nebulized 3% saline for 12 minutes and spit saliva and induced sputum into separate cups at 2-minute intervals. Researchers extracted RNA from the sputum cells and performed RNA sequencing. The researchers then used multilevel linear regression models to evaluate the association between sputum gene expression and clinical and demographic variables.
The results were published in the American Journal of Respiratory and Critical Care Medicine.
Gene expression of ACE2 was lower than that of TMPRSS2. Expression of both genes was similar between the participants with asthma and the healthy participants.
Among those with asthma, higher expression of both ACE2 and TMPRSS2 were associated with male sex, Black race and history of diabetes. Inhaled corticosteroid use was significantly associated with lower expression of both genes, but use of triamcinolone acetonide was not, according to the results.
Gene expression of ICAM-1 increased in participants with asthma. The researchers observed less consistent differences related to sex, race and ICS use with ICAM-1 expression.
“Higher expression of ACE2 and TMPRSS2 in these patient subgroups provides some biologic rationale for why these subgroups are at increased risk for poor COVID-19 outcomes and warrants further monitoring of these patient subgroups for poor COVID-19 outcomes,” Peters said. “Our findings provide rationale to test the use of inhaled corticosteroids as a potential strategy to decrease COVID-19 infections in patients with asthma.”