Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Bulk and Single-Cell Transcriptomics Identify Tobacco-Use Disparity in Lung 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)

How to cite: Cai, G. Bulk and Single-Cell Transcriptomics Identify Tobacco-Use Disparity in Lung Gene Expression of ACE2, the Receptor of 2019-nCov. Preprints 2020, 2020020051. https://doi.org/10.20944/preprints202002.0051.v2 Cai, G. Bulk and Single-Cell Transcriptomics Identify Tobacco-Use Disparity in Lung Gene Expression of ACE2, the Receptor of 2019-nCov. Preprints 2020, 2020020051. https://doi.org/10.20944/preprints202002.0051.v2

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 bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression 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 former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

Keywords

Wuhan 2019-nCov; ACE2; expression; susceptibility; race; age; gender; smoking; single cell

Subject

Biology and Life Sciences, Immunology and Microbiology

Comments (3)

Comment 1
Received: 14 February 2020
Commenter: Guoshuai Cai
Commenter's Conflict of Interests: Author
Comment: More datasets were analyzed and new conclusions were developed
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Response 1 to Comment 1
Received: 19 February 2020
Commenter: T.K.
The commenter has declared there is no conflict of interests.
Comment: the following paper may or may not be related to this.

Association of Smoking With Aortic Wave Reflection and Central Systolic Pressure and Metabolic Syndrome in Normotensive Japanese Men
https://pubmed.ncbi.nlm.nih.gov/19325535-association-of-smoking-with-aortic-wave-reflection-and-central-systolic-pressure-and-metabolic-syndrome-in-normotensive-japanese-men/
Comment 2
Received: 15 February 2020
Commenter: Richard Spelling
The commenter has declared there is no conflict of interests.
Comment: I read your "Bulk and Single-Cell Transcriptomics Identify Tobacco-Use Disparity in Lung Gene Expression of ACE2, the Receptor of 2019-nCov" with interest.

I have noticed that there are essentially zero deaths outside of China so far. Let me explain. There was one in PH, a Chinese man, one in Hong Kong, presumably a Chinese national, one in Japan, an 80 year old Japanese woman, and one in France, an 80 year old Chinese tourist.

As of today, there are 584 cases outside China. Only the 4 deaths above. It took the Chinese doctor 26 days to die after his first cough. It has been 25 days since the first case outside of China, on Jan 12. Statistically, SOME of the people outside of China should have died already, even if you go by the "official" Chinese numbers for fatality rate.

I have a theory.

Basically, everyone who has died (so far) lived in a Chinese city, with heavy air pollution.

The pollution in the air in the Chinese cities is acting like the smoking in your paper, making everyone living in those cities basically a smoker. Smoking in general makes you more sustainable to respiratory infections, and makes them worse when you do get them.

That, combined with the overloaded hospital system there, is making it far far worse.

Thoughts?
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Comment 3
Received: 29 March 2020
Commenter:
The commenter has declared there is no conflict of interests.
Comment: I think that it would be more usefull if you can monitor the expression of ACE2 in lungs during the course of therapeutic management of a hospitalized COVID-19 patient (especially in ICU) and evaluate the gender differences, instead of measuring the ACE2 expression in lungs with adenocarcinoma and compare the results according to gender at least. Maybe there will be differences concerning ACE2 expression between male and female during the ICU phase of therapy as women have diploid gene for ACE2 while men have aploid. This means probably that men are more easily depleted of activating genes for ACE2 expression and thus their lung pressure cannot be controlled the same succesful way that women's lung can. If this hypothesis is correct then a rhACE2 may be useful in the management of COVID-1 patients especially males in critical respiratory condition.
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