COVID19 Severity – Are Smokers at Risk?
Beginning of 2020 will be known for the pandemic of COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2). Symptoms can be mild to severe, and all of us are aware of guidelines that should be followed to prevent spreading the virus and getting sick.
But when the virus gets into our body, how does it enter our cells and start to replicate?
Through angiotensin-converting enzyme 2 (ACE2) receptor. We can find this receptor in different tissues, mainly lung, liver, kidneys, gastrointestinal tract and brain.
Let’s go quickly back to 2003 when the virus from the same family, SARS CoV, caused the epidemic and more than 8000 cases in the world with approximately 10% fatality rate and it had more severe symptoms than this one we are coping with today. Researchers developed a mouse model to study its pathogenesis and vaccine efficacy. It was a transgenic mice model with human ACE2 (hACE2) receptor expression in epithelial cells since the mouse ACE2 receptor doesn’t bind the virus with the same efficacy.
The main question was if the level of expression of hACE2 receptor influence the severity of the disease.
Mice had three different levels of hACE2 transgene copies and were inoculated with the virus intranasally. Virus titers in lungs were higher in mice with bigger number of hACE2 copies and they developed more severe symptoms, also lethal ones earlier than other groups. The virus was not detected in epithelial cells of liver, kidneys and intestine, but in later days after inoculation, it was detected in the brain as a secondary target for SARS-CoV. Treating mice with human anti-SARS CoV monoclonal antibody a day prior to infection resulted in disease prevention. However, virus replication was enhanced in airways cells with high hACE2 expression and resulted in increased inflammatory cells infiltration, epithelial cells proliferation and elevated cytokine and chemokine production.
Now, 17 years later, we are fighting against another coronavirus that causes more severe symptoms in elderly patients. Can we explain this with ACE2 receptor expression? Studies on humans, mice, rats and rodents showed that expression of this receptor is not affected by sex or age. On the contrary, cigarette smokers showed increased levels of ACE2 receptors in the lungs compared to non-smokers. How do we explain this higher expression? Many cell types build our lungs and respiratory epithelium and not all of them carry this receptor but its expression is shown in the secretory club, goblet cells and alveolar type 2 cells of lung epithelium. Exposure to cigarette smoke during in vitro differentiation of these cells resulted in enhanced cell proliferation and hyperplasia.
We still need to investigate this disease in more detail but partially we can explain susceptibility to severe form of COVID-19 in smokers with upregulated expression of ACE2 receptor. This effect is dose-dependent since expression was higher in cells exposed longer to cigarette smoke and in smokers with higher cigarette consumption. It is also reversible because in former smokers decrease in ACE2 receptor expression was observed, so it would mean that quitting smoking could decrease the risk of developing more severe disease.
We are all aware of the bad effect smoking has on our body and health but here is another reason while quitting is worthwhile. Furthermore, cigarette smoke can have an immunomodulatory effect and can suppress the immune response of smokers. Chronic inflammation can be a result of the exposure to smoke and that is also correlated with proinflammatory changes in glycans about which you can read more following this link.
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