Michael C Peters , Satria Sajuthi , Peter Deford , Stephanie Christenson , Cydney L. Rios , Michael T. Montgomery , Prescott G Woodruff , David T Mauger , Serpil C. Erzurum , Mats W Johansson , Loren C Denlinger , Show All…+ Author Information
Am J Respir Crit Care Med. 2020 Apr 29. doi: 10.1164/rccm.202003-0821OC. Online ahead of print.
Abstract
Background: Coronavirus disease 2019 (COVID-19) is caused by SARS-coronavirus 2 (SARS-CoV-2). Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity. Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls. Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes was similar in asthma and health. Among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide (TA) did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to gender, race, and use of ICS. Conclusion: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID19 outcomes. 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 COVID19 morbidity.