Article
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Preserved in Portico This version is not peer-reviewed
Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov
Version 1
: Received: 3 February 2020 / Approved: 5 February 2020 / Online: 5 February 2020 (02:56:53 CET)
Version 2 : Received: 12 February 2020 / Approved: 14 February 2020 / Online: 14 February 2020 (04:32:49 CET)
Version 3 : Received: 27 February 2020 / Approved: 2 March 2020 / Online: 2 March 2020 (01:38:52 CET)
Version 2 : Received: 12 February 2020 / Approved: 14 February 2020 / Online: 14 February 2020 (04:32:49 CET)
Version 3 : Received: 27 February 2020 / Approved: 2 March 2020 / Online: 2 March 2020 (01:38:52 CET)
How to cite: Cai, G. Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov. Preprints 2020, 2020020051. https://doi.org/10.20944/preprints202002.0051.v1 Cai, G. Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov. Preprints 2020, 2020020051. https://doi.org/10.20944/preprints202002.0051.v1
Abstract
In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed four large-scale datasets of normal lung tissue to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression. No significant disparities in ACE2 gene expression were found between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in smoker samples compared to non-smoker samples. This indicates the smokers may be more susceptible to 2019-nCov and thus smoking history should be considered in identifying susceptible population and standardizing treatment regimen.
Keywords
Wuhan 2019-nCov; ACE2; expression; susceptibility; race; age; gender; smoking
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: Tiantian Qin
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Thank you for the contribution to the virus study. I think this is a significant research.
I wonder whether the data is open to the public as well? I am teaching a statistic course on linear regression and will be very interested in the analyse method. I would really appreciate it if I could get the data (or a portion of data) for academic study purpose.
Thank you very much!
Tiantian Qin, PhD
Senior Lecturer
Department of Statistics
Purdue University
Commenter: Leo Hopkins
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Commenter: Guoshuai Cai
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Commenter: SFN
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And isn't it also the case that there are legitimate, well-established differences in ACE2 allele frequencies (and thus gene expression) between those of different ethnicities?
Both of these factors would appear to indicate the opposite of what was found in this review. I will be very interested to see the results of further research on this topic.
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So e-cigarettes, patches etc may be just as problematic as smoking in this regard.
This upregulation also has implications regarding blood pressure control, incidentally.
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Commenter: k raghavendra singh
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Commenter: Klaus K.
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Does the author have an explanation for his unexpected finding?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295500/
Commenter: David Holley
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Commenter: Michelle Minton
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ACE2 is part of the crucial compensatory axis that, when working properly, act to inhibit RAS and vasoconstriction. For example, moderate cardiovascular exercise, which like nicotine causes transient vasoconstriction, appears to trigger the upregulation of ACE2. [1]
Thus, ACE2, even if high levels make one more susceptible to SARS-CoV-2 infection, may also play an important beneficial role in ameliorating the effects of severe COVID-19. [2] Presumably, how ACE2 affects COVID-19 progression is more important to mortality risk in patients with a pre-existing imbalance of RAS and the compensatory axis, such as those with hypertension, heart diseases, or kidney disease. But, this is only something that will hopefully be answered by clinical trials currently underway. Until then, I don't think it would responsible to jump to conclusions about how ACE2 levels (or anything that alters ACE2 levels) affects COVID-19 susceptibility or mortality.
[1] Daniel Massote Magalhãesa, et al. Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system. Heliyon, January 2020. DOI: 10.1016/j.heliyon.2020.e03208. https://www.sciencedirect.com/science/article/pii/S2405844020300530.
[2] Muthiah Vaduganathan, et al. Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. NEJM March 2020. DOI: 10.1056/NEJMsr2005760. https://www.nejm.org/doi/full/10.1056/NEJMsr2005760.
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Commenter: Baran Ozmen
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Commenter: Simon Edge
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So, 48% of Chinese males are smokers (which is a huge percentage), whereas only 5% of Chinese women smoke - this could be the answer to this puzzle...
Commenter: Tim G.
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Commenter: WD Aguilar
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Commenter: Katharine O'rouke
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The above research coming from actual case studies shows that smokers represent only approx 2% of mortalities.
Smoking it seems likeli confers a benefit with respect to this coronavirus. Smoking has played a significant plague inhibiting role in the past including in the case of the black death.
Commenter: Shelby Moore III
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https://www.medrxiv.org/content/10.1101/2020.02.06.20020974v1.full.pdf#page=21
Commenter: Shannon Purkey
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Commenter: Santiago Vaca
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Commenter: Rebecca Lee
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Commenter: Steph Squires
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Since higher expression of ACE2 is not normal for smokers according to the extensive prior research, a high expression in the normal cells of cancer patients, which you found, could help to explain the increased susceptibility of cancer patients to covid. It indicates that a cancer patient who is a smoker would be at higher risk.
Your presentation of the findings should clearly state the valid and important conclusions, especially those which could save a life. Those cancer patients who are smoking may be encouraged to quit, in hopes that ACE2 receptor expression will be reduced before they are exposed to the virus.
On the other hand, smokers should not be encouraged to quit during covid pandemic. This is obvious from the work on covid patients, indicating a reduced risk of hospitalization for current smokers, which is attributable to the known downregulation of ACE2 in smokers.
I think it is reasonable to advise smokers to be moderate or reduce smoking for the benefit of general lung health, however to suggest that quitting nicotine is timely, which would increase susceptibility to covid by upregulating ACE2, is wrong. Except for the cancer patients, they should wait until the danger of the pandemic is past.
It is concerning to see research misinterpreted by the media due to misunderstandings, especially in a way that puts the health of a population in jeopardy. The true conclusions should be made clear to everyone, so they can give appropriate cautions for the pandemic. The easy way to correct this issue is simply to add the words "in normal tissues of cancer patients" at the end of your title.
Thank you for your contribution to the research on ACE2, which is so important now! Be well, everyone.
Commenter: George Tee
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Commenter: Leigh Taylor Ward
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https://www.medrxiv.org/content/10.1101/2020.02.06.20020974v1.full.pdf The link gives you the fulle article written on the subject of the 2019 noCoVi outbreak in China. In Table 1 numbers are given for all kinds of categories of 2019 noCoVi patients:
41 out of 173 deaths also suffered from hypertension
28 out of 173 deaths also suffered from diabetes
10 out of 173 deaths also suffered from coronary heart disease
29 out of 172 deaths were current smokers
Are there any overlaps in these numbers? For example: did 28 out of the 41 sufferers of hypertension also have diabetes? And did the 29 current smokers suffer from any of the above?
Reports about 1,099 COVID-19 patients in China discovered that most were also suffering from hypertension, coronary artery disease, diabetes and renal disease, all health problems that likely were being treated with ACEIs (angiotensin-converting enzyme inhibitor) or ARBs (angiotensin receptor blockers).
Similar reports have been coming out of Italy, where an estimated 52 percent of COVID fatalities were also taking an ACE inhibitor.
Dr Malcolm Kendrick, a UK GP, estimates that people who are taking any blood pressure medication are four times more likely to die from the virus.
People who are taking an ACE inhibitor or an ARB drug for heart problems should stay at home and not meet up with people, say researchers from Louisiana State University.
The drugs also increase the chances of catching the virus in the first place. ACEIs in particular increase the receptors around the lungs that the corona virus also binds to, the ACE2s.
Many taking the medication are elderly and are being treated for cardiovascular diseases including a heart attack, high blood pressure (hypertension), diabetes or chronic kidney disease. The ARBs are also prescribed to reduce blood pressure levels.
https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taaa041/5809509
So if one is a smoker (which means less ACE2 receptors) and one leads an otherwise healthy lifestyle then a smoker is less likely to die from 2019 noCoVi. If that smoker also drinks a lot, eats a lot of junk food, uses medical drugs then he is probably as likely or more so to die from 2019 noCoVi (called CoVid-19 in Europe).
Begs the question: what influence does lifestyle and medicine use have on your changes of surviving 2019 noCoVi?
I wish we would see more articles like the one from China with numbers in categories, especially from countries like Germany, France, UK, Netherlands, Canada or USA.
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Commenter: Francesca Manning
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Various studies have shown that nicotine stimulates the cholinergic anti-inflammatory pathway thus blocking the cytokine storm responsible for covid-19 deaths. Therefore it is surely more likely that smokers are simply not getting as sick as non-smokers, due to the anti-inflammatory role played by nicotine.
Commenter: Robert C. Speth
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