Preprint Article Version 3 This version is not peer-reviewed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 (doi: 10.20944/preprints202002.0051.v3). 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 (doi: 10.20944/preprints202002.0051.v3).

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 five 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.

Subject Areas

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

Comments (4)

Comment 1
Received: 2 March 2020
Commenter: Guoshuai Cai
Commenter's Conflict of Interests: Author
Comment: More analyses on data from healthy smokers and non-smokers are included.
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Comment 2
Received: 7 March 2020
The commenter has declared there is no conflict of interests.
Comment: Are you able to determine if non-smokers who are asthmatic express more ACE2? And if so, are they equally likely be severely affected by Covid-19?
Is ACE2 expression higher in asthmatics of any race or gender..? .
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Comment 3
Received: 29 March 2020
Commenter: Matthew Brown
The commenter has declared there is no conflict of interests.
Comment: Thank you for this research. Do you know if using nicotine products such as gum or patches will put someone in the current smoker category or the former smoker category. There’s much confusion currently on best path forward for current smokers. Should one quit right now because of the potential co-morbidity of smoking or continue to avoid a more significant Covid infection? Would nicotine supplementation alone keep ACE2 levels down?
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Response 1 to Comment 3
Received: 4 April 2020
The commenter has declared there is no conflict of interests.
Comment: Current data (February 12 – March 28, 2020) from the CDC [1] Table 1
Underlying health condition/Risk factor for severe outcomes from respiratory infection
Total with completed information (7,162) (no., % with condition)
Current smoker (96, 1.3%): Not hospitalized 61 (1), Hospitalized, non-ICU 22 (2), ICU admission 5 (1), Hospitalization status unknown 8 (2)
Former smoker (165, 2.3%): 80 (2) 45 (4) 33 (7) 7 (1)
Expected number of smokers would be around 981 (13.7% prevalence according to [2]). The difference between actual and expected numbers is even higher than in [3].

[1] https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e2.htm?s_cid=mm6913e2_w#T1_down
[2] https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm
[3] https://www.nejm.org/doi/10.1056/NEJMoa2002032

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