In patients with coronavirus disease 2019 (COVID-19), higher sputum cell expression of angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) was observed in certain patients with asthma while lower expression was found in patients who used inhaled corticosteroids (ICS), according to study results published in the American Journal of Respiratory and Critical Care Medicine.
COVID-19, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may be more severe in patients with chronic lung disease, including patients with asthma, and it appears that demographic or biological factors influence susceptibility to the infection or severity of disease. Because ACE2 and TMPRSS2 mediate viral infection of host cells, researchers reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells in patients with asthma may identify subgroups at risk for COVID-19 morbidity.
By analyzing gene expression for ACE2 and TMPRSS2 as well as intercellular adhesion molecule 1 (ICAM-1) in sputum cells from 330 participants and 79 healthy control individuals, researchers found that gene expression of ACE2 was lower than TMPRSS2, and that expression levels of both genes were similar in patients with asthma and healthy individuals. In patients with asthma, however, men, African Americans, and people with diabetes had higher expression of ACE2 and TMPRSS2. In patients with asthma, ICAM-1 expression increased and there were fewer consistent differences related to sex, race, and ICS use. Use of ICS was associated with lower expression of ACE2 and TMPRSS2, while treatment with triamcinolone acetonide did not decrease expression of either gene or ICAM-1.
“Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID-19 outcomes,” the study authors wrote. “The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID-19 morbidity.”
Peters MC, Sajuthi S, Deford P, et al; for the National Heart, Lung, and Blood Institute Severe Asthma Research Program-3 Investigators. COVID-19 related genes in sputum cells in asthma: Relationship to demographic features and corticosteroids [published online April 29, 2020]. Am J Respir Crit Care Med. doi:10.1164/rccm.202003-0821OC