Data from COVID-19 patients indicate that smokers are at higher risk of complications. The researchers published an article in the journal Developmental Cell that one of the possible reasons is that smoking increases the gene expression of ACE2 (a protein that binds to SARS-CoV-2), which may promote COVID- 19 infections. The study shows that long-term smoking will increase the ACE2 protein in the lungs, which may lead to a higher incidence of patients.

 

The author of the article, Jason Sheltzer, a cancer geneticist at Cold Spring Harbor Laboratory, said: “Our results suggest why smoking populations often produce poor clinical results after being infected with the new coronavirus. We found that smoking caused a significant increase in ACE2 expression, and ACE2 is a protein used by SARS-CoV-2 to enter human cells. ”

 

 

Sheltzer said: “Evidence from mouse experiments shows that high level of ACE2 expression makes mice more susceptible to SARS.” The latest study of SARS-CoV-2 found that when human-derived ACE2 is highly expressed in mice, mice infected with new coronavirus died faster. ”

 

The lung is one of the main organs for ACE2 expression. To assess the direct effect of smoking on the expression of ACE2 in the lung, Sheltzer compared the expression of ACE2 gene in the lung epithelial tissues of regular smokers and never smokers. Sheltzer said: “We found that smoking causes a significant increase in ACE2 expression,” he pointed out that smokers produce 30% -55% more ACE2 than nonsmokers. This change is also dose-dependent, that is, heavy smokers have the highest ACE2 expression levels. The effect of smoking on ACE2 may be related to goblet cells in the lungs. Sheltzer said: “The goblet cells produce mucus to protect the respiratory tract from inhalation. Therefore, the increased expression of ACE2 in the lungs of smokers may be a by-product of secretory cell proliferation caused by smoking.” Increased ACE2 is also associated with inflammation lung disease COPD and idiopathic pulmonary fibrosis.

 

In addition, Sheltzer’s results indicate that other viral infections (such as influenza) and interferon signaling (parts of the human viral defense system) can increase ACE2 expression. Sheltzer said: “Therefore, SARS-CoV-2 may trigger the up-regulation of its own receptors, thereby forming a positive feedback loop, leading to more infections.”

 

Although smoking has a significant effect on ACE2 expression, it is not permanent. By comparing the lungs of smokers with those of people who quit smoking for at least 12 months, Sheltzer found that “ACE2 expression decreased significantly, indicating that smoking cessation can reverse the promotion of smoking to increase the expression of ACE2.”

 

 

Reference

Joan C. Smith et al, Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract, Developmental Cell (2020). DOI: 10.1016/j.devcel.2020.05.012