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COVID-19 and nicotine as a mediator of ACE-2

Published time: 04 June 2020

Authors: Janice M. Leung, Chen Xi Yang, Don D. Sin

Keywords: smokers, nicotine, ACE-2, Covid-19.


Abstract

We recently reported that current smokers and those with COPD had higher airway epithelial cell expression of the angiotensin-converting enzyme II (ACE-2) viral entry receptor. We thus read with great interest the work of P. Russo and co-workers, which proposes a mechanism for this finding, namely that this upregulation is mediated by nicotine exposure specifically through the α7 subtype of nicotine acetylcholine receptors (α7-nAChR). While exposure to increasing concentrations of nicotine caused epithelial cells to increase ACE-2 levels, subsequent gene silencing of α7-nAChR appeared to significantly dampen this response. A secondary transcriptome sequencing analysis of our cohort (consisting of 42 subjects who underwent bronchoscopy for epithelial cell brushings) reveals evidence in support of this hypothesis. We found that airway epithelial cell expression of CHRNA7, encoding α7-nAChR, was significantly correlated with the expression of ACE2 (Pearson r=0.54, p=2.31×10−8). There was significantly higher CHRNA7 expression in those with COPD (2.75±0.73 versus 2.14±0.43 in those without COPD; p=1.47×10−4), with a trend towards higher expression in current smokers compared to former and never smokers (2.86±0.92 in current smokers, 2.35±0.57 in former smokers, and 2.27±0.45 in never smokers; p=6.16×10−2). CHRNA7 was also negatively correlated with forced expiratory volume in 1 s percent predicted (Pearson r=−0.37, p=2.83×10−4). Interestingly, CHRNA7 was positively if weakly correlated with body mass index (Pearson r=0.14, p=6.31×10−3), raising the intriguing possibility that nicotine receptor mediation of ACE-2 may also be related to why obese individuals have made up a considerable proportion of coronavirus disease 2019 (COVID-19) cases


COVID-19 and nicotine as a mediator of ACE-2

 

Reference: https://doi.org/10.1183/13993003.01261-2020

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