Association of Cigarette Smoking, COPD, and Lung Cancer With Expression of SARS-CoV-2 Entry Genes in Human Airway Epithelial Cells.

Junping Yin,Xinhua Yu,Frank Petersen,Brigitte Kasper

doi:10.3389/fmed.2020.619453

Junping Yin, Xinhua Yu + Show 2 more

Open Access

https://doi.org/10.3389/fmed.2020.619453

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Abstract

SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.

Highlights

In December 2019, a cluster of viral pneumonia cases which is featured by pulmonary parenchymal opacities at chest radiography was reported in Wuhan, China [1]
Our objective is to explore the effect of on the expression of three genes essentially involved in SARSCoV-2 entry, namely angiotensin converting enzyme 2 (ACE2), TMPRSS2, and cathepsin L in human airway epithelial cells isolated from non-smoker, smoker, and patients with cigarette smoking (CS)-induced diseases
We examined expression levels of ACE2, TMPRSS2, and cathepsin L in human airway epithelial cells derived from never smokers, former smokers, current smokers, patients with COPD, or lung cancer

Summary

Introduction

In December 2019, a cluster of viral pneumonia cases which is featured by pulmonary parenchymal opacities at chest radiography was reported in Wuhan, China [1]. Expression of SARS-CoV-2 Entry Genes cases of COVID19 worldwide with more than one million deaths [4]. SARS-CoV-2 shares ∼80% sequence identify to SARSCoV and both viruses use the same cell entry receptor, namely angiotensin converting enzyme 2 (ACE2) [5, 6]. As the receptor of SARS-CoV and SARS-CoV-2, ACE2 mediates the viral entry via two major pathways, cathpesin L-dependent endocytosis and transmembrane serine protease 2 (TMPRSS2) dependent membrane fusion [7,8,9]. Since COVID-19 is an acute disease resulted from respiratory tract infection of SARS-CoV-2, the interaction between the spike protein (S protein) of the virus and the ACE2 on human airway epithelial cells could be a crucial step for the development of the disease [10, 11]

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