Expression of the SARS-CoV-2 <i>ACE2</i> Receptor in the Human Airway Epithelium

Abstract

<b>Rationale:</b> 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 <i>ACE2</i> (angiotensin-converting enzyme 2) on the airway epithelium.<b>Objectives:</b> The objective was to gain insight into the expression of <i>ACE2</i> in the human airway epithelium.<b>Methods:</b> Airway epithelia sampled by fiberoptic bronchoscopy of trachea, large airway epithelia (LAE), and small airway epithelia (SAE) of nonsmokers and smokers were analyzed for expression of <i>ACE2</i> and other coronavirus infection-related genes using microarray, RNA sequencing, and 10x single-cell transcriptome analysis, with associated examination of <i>ACE2</i>-related microRNA.<b>Measurements and Main Results:</b><i>1</i>) <i>ACE2</i> is expressed similarly in the trachea and LAE, with lower expression in the SAE; <i>2</i>) in the SAE, <i>ACE2</i> is expressed in basal, intermediate, club, mucus, and ciliated cells; <i>3</i>) <i>ACE2</i> is upregulated in the SAE by smoking, significantly in men; <i>4</i>) levels of miR-1246 expression could play a role in <i>ACE2</i> upregulation in the SAE of smokers; and <i>5</i>) <i>ACE2</i> is expressed in airway epithelium differentiated <i>in vitro</i> 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.<b>Conclusions:</b><i>ACE2</i>, 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.