Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium.

RATIONALE: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. OBJECTIVES: The objective was to gain insight into the expression of ACE2 in the human airway epithelium. METHODS: Airway epithelium sampled by fiberoptic bronchoscopy of trachea, large airway epi-thelium (LAE) and small airway epithelium (SAE) of nonsmokers and smokers was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA-seq and 10x single cell transcriptome analysis, with associated examination of ACE2-related miRNA. MEASUREMENTS AND MAIN RESULTS: (1) ACE2 is expressed similarly in the trachea and LAE with lower expression in the SAE; (2) in the SAE, ACE2 is expressed in basal, intermediate, club, mu-cus and ciliated cells; (3) ACE2 is up-regulated in the SAE by smoking, significantly in males; (4) levels of miR-1246 expression could play a role in ACE2 up-regulation in the SAE of smokers; and (5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers. CONCLUSIONS: ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).