E-Cigarette Vapour Increases ACE2 and TMPRSS2 Expression in a Flavour- and Nicotine-Dependent Manner

Abstract

COVID-19 infects via the respiratory system, but it can affect multiple systems and lead to multi system failure. There is growing evidence that smoking may be associated with higher rates of COVID-19 infections and worse outcomes due to increased levels of ACE2 in lung epithelial cells, but it is unknown whether E-cigarette use may lead to increased risk of COVID-19 infection from the SARS-CoV-2 virus. In this study, healthy donor bronchial epithelial cells (NHBE) and monocyte-derived macrophages (MDM) were exposed to cigarette smoke extract (CSE) or nicotine or flavoured E-cigarette vapour extract (EVE) before the assessment of SARS-CoV-2 recognition receptors ACE2 and TMPRSS2 genes. MDMs exposed to CSE and Tobacco EVE showed increased ACE2 expression; however, no treatment altered the TMPRSS2 expression. ACE2 was found to be upregulated by >2-fold in NHBE cells exposed to CSE, as well as nicotine, banana, or chocolate EVE, while TMPRSS2 was only upregulated by CSE or nicotine EVE exposure. These findings suggesting that flavourings can increase ACE2 expression in multiple cell types, while TMPRSS2 expression increases are limited to the epithelial cells in airways and may be limited to nicotine and/or cigarette smoke exposure. Therefore, increased risk of COVID-19 infection cannot be ruled out for vapers.

Curbside particulate matter and susceptibility to SARS–CoV-2 infection

“…Compatible with this speculation, we found that the antioxidant N-acetyl cysteine attenuated PM 10 -stimualted ACE2 expression. Furthermore, we found that CSE, a known source of oxidative stress, 15 , 16 increased ACE2 expression in both A549 cells and HPNEpCs. Indeed, in HPNEpCs, CSE 5% was the more potent stimulus of ACE2 expression.…”

“…In this study, we sought to assess the effect of curbside PM 10 on ACE2 expression in human nasal epithelial airway cells, and in Vero-E6 cells we sought to determine whether curbside PM 10 increases susceptibility to SARS-CoV-2 infection. The effect of cigarette smoke extract (CSE) was also assessed because it is a source of oxidative stress, 15 it increases ACE2 expression in primary airway epithelial cells in vitro , 16 and ACE2 expression is increased in the lower airway of smokers. 17 …”