Effects of Smoking on ACE2 Expression Pattern: Risk and Severity of SARS-CoV-2 Infection

Li, Wenjuan; Zheng, Rui; Liang, Rongpu; Wu, Biao; Wang, Chengqiang; Zhuo, Li; Wu, Maosheng; Jie, Yusheng; Lin, Bingliang; Chang, Lihong; Yang, Qintai; Wei, Bo; Zhou, Yuqi

BACKGROUND: Respiratory epithelium expressing angiotensin-converting enzyme 2 (ACE2) is the entry for novel coronavirus (SARS-CoV-2), pathogen of the COVID-19 pneumonia outbreak, although a few recent studies have found different ACE2 expression in lung tissue of smokers. The effect of smoking on ACE2 expression and COVID-19 is still not clear. So, we did this research to determine the effect of smoking on ACE2 expression pattern and its relationship with the risk and severity of COVID-19. METHODS: The clinical data of COVID-19 patients with smoking and non-smoking were analyzed, and ACE2 expression of respiratory and digestive mucosa epithelia from smoker and non-smoker patients or healthy subjects were detected by immunohistochemical (IHC) staining. RESULTS: Of all 295 laboratory-confirmed COVID-19 patients, only 24 (8.1%) were current smokers with moderate smoking or above, which accounted for 54.2% of severe cases with higher mortality than non-smokers (8.3% vs. 0.4%, p = 0.018). Data analysis showed the proportion of smokers in COVID-19 patients was lower than that in general population of China (Z = 11.65, P < 0.001). IHC staining showed ACE2 expression in respiratory and digestive epithelia of smokers were generally downregulated. CONCLUSIONS: The proportion of smokers in COVID-19 patients was lower, which may be explained by ACE2 downregulation in respiratory mucosa epithelia. However, smoking COVID-19 patients accounted for a higher proportion in severe cases and higher mortality than for non-smoking COVID-19 patients, which needs to be noted.