Joan C Smith, Jason Meyer Sheltzer

The coronavirus SARS-CoV-2 has infected more than 600,000 people and has overwhelmed hospital systems around the world. However, the factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of epithelial cells that line the respiratory tract, including goblet cells, club cells, and alveolar type 2 cells. Chronic smoke exposure triggers a protective expansion of mucus-secreting goblet cells and a concomitant increase in ACE2 expression. In contrast, quitting smoking causes a decrease in lung ACE2 levels. Taken together, these results may partially explain why smokers are particularly likely to develop severe SARS-CoV-2 infections, and they suggest that quitting smoking could lessen coronavirus susceptibility.

doi: https://doi.org/10.1101/2020.03.28.013672
This article is a preprint and has not been certified by peer review