ABSTRACT
Evidence in humans suggests a correlation between nicotine smoking and severe respiratory symptoms with COVID-19 infection. In lung tissue, angiotensin-converting enzyme 2 (ACE2) appears to mechanistically underlie viral entry. Here, we investigated whether e-cigarette vapor inhalation alters ACE2 and nicotinic acetylcholine receptor (nAChR) expression in male and female mice. In male lung, nicotine vapor inhalation induced a significant increase in ACE2 mRNA and protein, but surprisingly, these differences were not found in females. Further, both vehicle and nicotine vapor inhalation downregulated α5 nAChR subunits in both sexes, while differences were not found in α7 nAChR subunit expression. Finally, blood ACE2 levels did not differ with exposure, indicating that blood sampling is not a sufficient indicator of lung ACE2 changes. Together, these data indicate a direct link between e-cigarette vaping and increased ACE2 expression in male lung tissue, which thereby reveals an underlying mechanism of increased vulnerability to coronavirus infection in individuals vaping nicotine.
Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/epidemiology , Electronic Nicotine Delivery Systems , Lung/enzymology , Vaping/adverse effects , Angiotensin-Converting Enzyme 2/blood , Angiotensin-Converting Enzyme 2/genetics , Animals , DNA, Complementary/biosynthesis , Female , Lung/cytology , Male , Mice , Mice, Inbred C57BL , Nicotine/administration & dosage , Nicotine/pharmacology , Nicotinic Agonists/administration & dosage , Nicotinic Agonists/pharmacology , Receptors, Nicotinic/biosynthesis , Sex Characteristics , alpha7 Nicotinic Acetylcholine Receptor/metabolismSubject(s)
Betacoronavirus/drug effects , Coronavirus Infections/diet therapy , Coronavirus Infections/prevention & control , Diet, Gluten-Free , Glutens/administration & dosage , Pandemics/prevention & control , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/diet therapy , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/genetics , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Angiotensin-Converting Enzyme 2 , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Databases, Factual , Enterocytes/drug effects , Enterocytes/metabolism , Gene Expression Regulation/drug effects , Host-Pathogen Interactions/drug effects , Humans , Nicotine/administration & dosage , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Spike Glycoprotein, Coronavirus/metabolism , Tobacco Smoking/metabolismABSTRACT
Statistical surveys of COVID-19 patients indicate, against all common logic, that people who smoke are less prone to the infection and/or exhibit less severe respiratory symptoms than non-smokers. This suggests that nicotine may have some preventive or modulatory effect on the inflammatory response in the lungs. Because it is known that the response to, and resolution of the SARS-CoV-2 infection depends mainly on the lung macrophages, we discuss the recent scientific findings, which may explain why and how nicotine may modulate lung macrophage response during COVID-19 infection.