Mounting evidence suggests that, compared with nonsmokers, people who smoke cigarettes face a higher risk of developing severe complications and dying from COVID-19 infections.
For instance, a study of more than 1,000 patients in China, published in the New England Journal of Medicine, found that smokers with COVID-19 were more likely to require intensive medical interventions than those who didn’t smoke. In the study, 12.3% of current smokers were admitted to Intensive Care Units (ICUs), were placed on a ventilator or died, as compared with only 4.7% of nonsmokers.
Smokers may be particularly vulnerable to COVID-19 for several reasons, but the ACE2 receptor hypothesis provides a holistic, mechanistic link between smoking and severe infection, suggest authors. In this way, if future research bolsters the link between receptor quantity and disease severity, drugs that block or reduce the sensitivity of ACE2 receptors could potentially be used as treatments.
As age and sex appeared unrelated to ACE2 quantity, the researchers wondered if cigarette smoke exposure might make a difference.
The team inspected tissue samples from mice that had been exposed to diluted cigarette smoke for zero, 2, 3 or 4 hours a day over the course of five months. They found that, the more smoke exposure, the more ACE2 receptors studded the animals’ lungs. Compared with unexposed mice, the mice that received the highest dose of cigarette smoke accumulated about 80% more ACE2 receptors in their lungs. The researchers then compared the lungs of human smokers against those who never smoked, and again, they found a similar trend: smokers’ lungs contained 40% to 50% more ACE2 receptors than those of nonsmokers.
The quantity of ACE2 receptors varied by pack-years ― a measure of how many packs of cigarettes a person smoked per day multiplied by the number of years the person smoked. For example, among smokers who had undergone thoracic surgery, people who smoked more than 80 pack-years showed a 100% increase in ACE2 receptors compared with people who smoked fewer than 20 pack-years, the authors noted.
While smoke-exposed tissues harbored more ACE2 receptors, the team could not tell which specific cells contained the receptor. By examining which proteins appeared in what cells, the team found that ACE2 appeared on cells that process oxygen and carbon dioxide in the lungs, known as alveolar type 2 cells. But primarily, the receptors appeared on cells that secrete a mucus-like fluid into the respiratory tracts, known as goblet and club cells. Nonsmokers carry most of their goblet and club cells in their nose and throat, but in smokers, the cells begin to accumulate also in the lungs, the authors found.
Evidence that smoking boosts the number of secretory cells in the lungs has been reported for decades, according to a 1999 report in the American Journal of Respiratory and Critical Care Medicine ―the sticky mucus generated by goblet and club cells acts as a protective barrier, capturing debris, aerosols, smoke and pathogens that get sucked into the respiratory system―. When people inhale smoke into their lungs, the organ reinforces its defenses by building more secretory cells and increasing mucus production. Besides, the same process occurs in individuals exposed to high levels of air pollution.
Link to the paper: https://doi.org/10.1056/NEJMoa2002032
Editorial Disclaimer: information published during the 2020 COVID-19 pandemic may be updated frequently to reflect the dynamic nature of current understanding.
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