TY - JOUR
T1 - COVID-19-related genes in sputum cells in asthma
T2 - Relationship to demographic features and corticosteroids
AU - NHLBI Severe Asthma Research Program-3 Investigators
AU - Peters, Michael C.
AU - Sajuthi, Satria
AU - Deford, Peter
AU - Christenson, Stephanie
AU - Rios, Cydney L.
AU - Montgomery, Michael T.
AU - Woodruff, Prescott G.
AU - Mauger, David T.
AU - Erzurum, Serpil C.
AU - Johansson, Mats W.
AU - Denlinger, Loren C.
AU - Jarjour, Nizar N.
AU - Castro, Mario
AU - Hastie, Annette T.
AU - Moore, Wendy
AU - Ortega, Victor E.
AU - Bleecker, Eugene R.
AU - Wenzel, Sally E.
AU - Israel, Elliot
AU - Levy, Bruce D.
AU - Seibold, Max A.
AU - Fahy, John V.
N1 - Publisher Copyright:
Copyright © 2020 by the American Thoracic Society
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity. Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma. Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP-3 (Severe Asthma Research Program-3) and 79 healthy control subjects. Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were 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 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 sex, race, and use of ICS. Conclusions: 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 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.
AB - Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity. Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma. Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP-3 (Severe Asthma Research Program-3) and 79 healthy control subjects. Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were 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 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 sex, race, and use of ICS. Conclusions: 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85084617109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084617109&partnerID=8YFLogxK
U2 - 10.1164/rccm.202003-0821OC
DO - 10.1164/rccm.202003-0821OC
M3 - Article
C2 - 32348692
AN - SCOPUS:85084617109
SN - 1073-449X
VL - 202
SP - 83
EP - 90
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 1
ER -