Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2

Abstract

declared the coronavirus disease (COVID-19) outbreak a pandemic.As of May 28, 2020, laboratories had confirmed 5,701,337 COVID-19 cases, and 357,668 deaths had been reported in 216 countries, areas, or territories (1).COVID-19 is caused by a new type of pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is phylogenetically similar to SARS-CoV, with approximately 80% identity between the genomes (2).SARS viruses affect the respiratory tract and cause an acute respiratory response through the same cell-entry receptor, ACE2 (angiotensin-converting enzyme 2), which is the only experimentally confirmed SARS-CoV-2 receptor.SARS-CoV-2 infection also uses activation of the spike proteins found on the surface of the virus for cellular entry.The best candidates for priming spike proteins are two host cell enzymes called Furin and TMPRSS2 (2).In the current severe global emergency, to enable effective prevention and care, it is imperative to identify potential risk factors, such as cigarette smoking, which is a substantial risk factor for various important bacterial and viral infections.Some of the results of this study were previously published in preprint form (medRxiv, https://www.medrxiv.org/content/10.1101/2020.02.05.20020107v3). MethodsWe evaluated a comprehensive set of transcriptomic data sets to investigate the associations of smoking with ACE2, FURIN, and TMPRSS2 gene expression in lung tissues.Two data sets were generated using normal lung tissues from patients with lung adenocarcinoma: a Caucasian RNA-sequencing (RNA-seq) data set from The Cancer Genome Atlas (n = 48) (3) and an Asian RNA-seq data set from the Gene Expression Omnibus (GSE40419, n = 74) (4).We included three polyethnic microarray data sets of gene expression in healthy small airway epithelium samples (GSE63127, n = 230 [5]; GSE19667, n = 116 [6]; and GSE5058, n = 24 [7]) and large airway epithelium samples (GSE7895, n = 104 [8]).In addition, we analyzed three microarray data sets of samples derived from healthy subjects and patients with chronic obstructive pulmonary disease (COPD), including small airway epithelium samples from current smokers (from GSE5058, n = 26 [7]),