Abstract
Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.
Highlights
There is emerging evidence that both nicotine use and smoking status may have an impact on COVID-19 infection rates and hospitalizations, as well as disease severity and mortality
The aim of the present study was to evaluate the effect of smoke derived from cigarettes in bronchial epithelial cells on ACE-2 membrane protein expression by using an in vitro exposure setting resembling those conditions experienced by smokers in vivo and assessing the effects by using a high content screening approach
The expression of membrane ACE-2 is reduced in cells exposed to 10, 15 and 20 cigarette puffs compared to AIR exposed control (p values < 0.05)
Summary
There is emerging evidence that both nicotine use and smoking status may have an impact on COVID-19 infection rates and hospitalizations, as well as disease severity and mortality. With respect to the conceivable molecular mechanisms underlying the possible association between smoking and viral infection, several reports focused their attention on the possible modulatory effect of smoking on ACE-2 protein expression which has been proved to serve as possible receptor for virus entry into epithelial cells (Walls et al, 2020). Several discrepancies have been observed to this regard since some reports showed that smoking was associated with a significant increase of ACE-2 protein expression (Batlle et al, 2020; Guo et al, 2020) It should be taken into due account that in most cases no information on patients’ comorbidities and smoking habits are reported and in particular regarding in vitro studies and biopsies, the studies evaluated only total protein expression rather than its membrane localization (Leung et al, 2020a). The generalized advice to quit smoking as a measure to reduce health risk remains valid, the findings of the present study, together with the well-established immunomodulatory effects of nicotine, may offer a pharmaceutical role of nicotine as a potential treatment option in COVID-19 patients
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