A new study shows that exposure to e-cigarette vapors leads to increased levels of the coronavirus ACE-2 receptor in the lungs of mice, with nicotine increasing this increase in male mice.
E-cigarette use, or vaping, causes serious damage to the lungs. After a new coronavirus that causes the respiratory disease COVID-19 emerged last year, there were concerns about how vaping could affect the risk of infection and severity of symptoms. Some evidence suggests an increased risk of COVID-19 infection among those who vape. Studies also show a higher mortality rate from COVID-19 among men compared to women, and men are more likely to vape than women. However, there is no evidence of a link between the two observations.
Jefferson’s new study sheds some light on this, showing that exposure to e-cigarette vapor increases the level of coronavirus receptors in the lungs of male mice, especially if nicotine is present in the vapor. This may make it easier to contract the virus. The study was published in the Journal of Investigative Medicine on April 29.
Using a spike-like protein on its surface as a key, the new coronavirus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor found in the airway mucosa and opens its way into lung cells.
“Cigarette smokers have been shown to have higher levels of ACE-2 in their lungs, and smoking is a known risk factor for lung disease and infections,” says Pawan Sharma, PhD, and co-author of the study. “We wanted to find out if there was a similar effect with e-cigarettes or vaping, and if the effects observed were different in males and females.”
The researchers placed male and female mice in a box with an automated system that delivered precisely controlled amounts of e-cigarette vapor with or without nicotine for 30 minutes twice a day for 21 days. Compared to control mice that breathed room air, mice exposed to e-cigarette vapor showed inflammation of lung tissue and decreased lung function, confirming the dangers of vaping. These effects were observed regardless of whether nicotine was added to the vapor, indicating the inherently harmful nature of the chemicals in e-cigarette vapor.
There was also an increase in ACE-2 receptor levels in the lungs of male and female mice exposed to vapor. Although not tested in this study, higher levels of the ACE-2 receptor may make it easier for the virus to enter the respiratory tract, increasing susceptibility to infection.
Interestingly, the presence of nicotine in vapor further increased ACE-2 levels specifically in male mice.
The researchers demonstrated for the first time a potential difference between sex and the effects of vaping and nicotine on ACE-2 levels in vivo. Although further research is needed to understand the full complexity of COVID-19 risk factors, this result sheds light on important physiological differences that make one sex potentially more vulnerable.
“Our results provide a rationale for studying the effects of vaping on human lung ACE-2 levels,” says Dr. Sharma. “If a similar induction of ACE-2 is observed, it will provide further evidence that vaping is a risk factor for COVID-19 and help us understand how to prevent and mitigate infection in this population.”
One of the authors (Dr. Amir A. Zeki) is an associate editor of the Journal of Investigative Medicine. Dr. Zeki is also the co-founder of InVixa, Inc. a private startup company developing inhalation therapy for the prevention and treatment of COVID-19. The authors report no other conflicts of interest.
