Combustible and Electronic Cigarette Exposures Increase ACE2 Activity and SARS-CoV-2 Spike Binding

To the Editor: The outbreak of coronavirus disease (COVID-19) has extensively impacted global health. The spike protein on the surface of the causative pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a metallocarboxypeptidase, which is expressed in both mACE2 (membrane-anchored ACE2) and sACE2 (soluble ACE2) forms in the lung. Although mACE2 is responsible for viral entry, recent observations also suggest that sACE2 is involved, by its interaction with the spike protein, followed by receptor-mediated endocytosis of the viral particles (1). Tobacco use has been speculated as a risk factor for contracting SARS-CoV-2 infection and subsequent disease severity (2, 3), and electronic cigarettes (e-cigarettes) have been shown to induce harmful proteomic and immune changes in the lungs of vapers (4). In addition, the effect of vaping, and the role of nicotine, in the regulation of ACE2 expression has been demonstrated in animal models and cell culture systems (5–8). We therefore tested the hypothesis that combustible tobacco (e.g., cigarettes) and noncombustible e-cigarettes could affect ACE2 activity and subsequent SARS-CoV-2 infection. Some of our data have been reported previously at an international conference (9) and deposited in a preprint repository (https://doi.org/10.1101/2021.06.04.447156)