Single-Cell Expression Landscape of SARS-CoV-2 Receptor and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients.

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of and SARS-CoV-2-priming proteases and in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of , , and . Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that levels were highest in normal alveolar type 2 (AT2) cells and that was expressed in 65% of normal AT2 cells. Conversely, the expression of was highest and most frequently detected (75%) in lung cells with malignant features. -positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated , and the scavengers and . Notably, the viral scavenger was significantly positively correlated with expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.