ABSTRACT
The outbreak of coronavirus disease 2019 (COVID-19) has extensively impacted global health. The causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a transmembrane metallo-carboxypeptidase that is expressed in both membrane-anchored (mACE2) and soluble (sACE2) forms in the lung. Tobacco use has been speculated as a vulnerability factor for contracting SARS-CoV-2 infection and subsequent disease severity, whilst electronic cigarettes (e-cigarettes) have been shown to induce harmful proteomic and immune changes in the lungs of vapers. We therefore tested the hypothesis that combustible tobacco (e.g. cigarettes) and non-combustible e-cigarettes could affect ACE2 activity and subsequent SARS-CoV-2 infection. We observed that sACE2 activity was significantly higher in bronchoalveolar lavage fluid from both smokers and vapers compared to age-matched non-smokers. Exposure to cigarette smoke increased ACE2 levels, mACE2 activity, and sACE2 in primary bronchial epithelial cultures. Finally, treatment with either cigarette smoke condensate or JUUL e-liquid increased infections with a spike-coated SARS-CoV-2 pseudovirus. Overall, these observations suggest that tobacco product use elevates ACE2 activity and increases the potential for SARS-CoV-2 infection through enhanced spike protein binding.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* Co-first authors
FUNDING SOURCES: Funded by NIH/FDA HL120100, NIH/NHLBI HL135642, R01CA237652, 1DP5OD021385, NIH/FDA HL153698, an American Cancer Society Research Scholar Grant (to J.M.S.) and a New York Community Trust Grant (to J.M.S.).
DISCLAIMER: Research reported in this publication was supported in part by the National Institutes of Health (NIH) and the Family Smoking Prevention and Tobacco Control Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.
CONFLICTS OF INTEREST: No conflicts of interest, financial or otherwise, are declared by the authors.
