COVID-19 News: Smoking Increases Expression Of ACE2 Receptors And COVID-19 Risk While Inhaling Corticosteroids Decreases These Virus Binding Receptors
: An international study lead by researchers from 25 institutions in Europe, America and Australia have found that smoking increases ACE2 receptors expression while inhaling corticosteroids has the opposite effect of suppressing the expression of these virus binding receptors.
The study findings in brief found that genes encoding viral receptors and activating protease are increased in the nose compared to the bronchi in matched samples and associated with the proportion of secretory epithelial cells in cellular deconvolution analyses.
Significantly current or ex-smoking was found to increase expression of these genes only in lower airways, which was associated with a significant increase in the predicted proportion of goblet cells.
Both acute and second hand smoke exposure were found to increase ACE2 expression while inhaled corticosteroids decrease ACE2 expression in the lower airways. A strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified.
The study findings were published on a preprint server and are currently under peer review. https://www.medrxiv.org/content/10.1101/2020.08.31.20169946v1
The new research shows that the gene encoding angiotensin-converting enzyme 2 (ACE2), a protein that facilitates SARS-CoV-2 entry, is present at higher levels in the nose than in the bronchus, indicating that the nose may be more easily infected.
The study findings showed that smoking appears to increase the expression of this gene, specifically in the lower airways, while having no effects on expression in the nose, lead researcher Dr Alen Faiz from the Respiratory Bioinformatics and Molecular Biology Department of the University of Technology Sydney-Australia told media.
He added, "This may indicate that smokers may be at risk for a more severe course of the infection by allowing its spread to the lung where most of the damage occurs. This higher level of ACE2 in current smokers was shown to be lower in individuals that stop smoking for more than a month, indicating that quitting smoking may be beneficial to reducing the risk for severe COVID-19."
Dr Faiz warned that smoking just three cigarettes is sufficient to increase the levels of ACE2 within one day in adults.
Alarmingly the study’s preliminary data also suggested that second-hand smoke exposure of one-year-old children increased ACE2 expression in their airways.
At the same time the study showed that inhaled corticosteroids were found to decrease ACE2 expression over six months of treatment, which may help explain the observation that patients with obstructive airway diseases do not appear to be overrepresented among patients hospitalized with severe COVID-19.
Dr Faiz added, "The current study provides the first longitudinal evaluation of ACE2 expression in samples from the airways on a limited number of patients, which deserves expansion in subsequent studies.”
He however emphasized, it's not clear that higher expression of the ACE2 receptors is linked with the severity of COVID- 19 infection, "however, this is a
theory based on the known mechanism of COVID-19 infection."
Interestingly the study also found that ACE2 is co-expressed with an adjacent gene TMEM27 and is highly associated with a methylation site in the TMEM27 promoter indicating a possible co-regulation or interaction of the two genes that is independent of smoking status.
It should be noted that there was also another study by researchers from Cold Spring Harbor Laboratory that showed that cigarette smoke exposure and inflammatory signaling increase the expression of the Sars-Cov-2 receptor ACE2 in the respiratory tract. https://www.sciencedirect.com/science/article/pii/S1534580720304019#
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