RESUMO
IntroductionCoronavirus disease 2019 (COVID-19) is a respiratory infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus uses the angiotensin converting enzyme II (ACE-2) as the cellular entry receptor to infect the lower respiratory tract. Because individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID-19, we determined whether ACE-2 expression in the lower airways was related to COPD and cigarette smoking. MethodsUsing RNA-seq, we determined gene expression levels in bronchial epithelia obtained from cytologic brushings of 6th to 8th generation airways in individuals with and without COPD. We eternally validated these results from two additional independent cohorts, which used microarray technologies to measure gene expression levels from 6th to 12th generation airways. ResultsIn the discovery cohort (n=42 participants), we found that ACE-2 expression levels were increased by 48% in the airways of COPD compared with non-COPD subjects (COPD=2.52{+/-}0.66 log2 counts per million reads (CPM) versus non-COPD= 1.70{+/-}0.51 CPM, p=7.62x10-4). There was a significant inverse relationship between ACE-2 gene expression and FEV1% of predicted (r=-0.24; p=0.035). Current smoking also significantly increased ACE-2 expression levels compared with never smokers (never current smokers=2.77{+/-}0.91 CPM versus smokers=1.78{+/-}0.39 CPM, p=0.024). These findings were replicated in the two eternal cohorts. ConclusionsACE-2 expression in lower airways is increased in patients with COPD and with current smoking. These data suggest that these two subgroups are at increased risk of serious COVID-19 infection and highlight the importance of smoking cessation in reducing the risk.
