Cigarette smokers more susceptible to coronavirus, US researchers find
Friday, 3 April 2020
US researchers at Google, Inc. and Cold Spring Harbor Laboratory in New York, have discovered that smokers are more likely to be infected by the novel coronavirus, SARS-CoV-19, compared to non-smokers in human population.
In a study which analysed 1,099 laboratory-confirmed cases of COVID19, the researchers found that the lungs of smokers expressed a protein called angiotensin-converting enzyme 2 (ACE2), which serves as an enzyme receptor in the regulation of blood pressure and where SARS-CoV-19 is naturally known to bind resulting into coronavirus disease (COVID-19).The study was archived in the preprint server for biology and released to the public on March 31st, 2020 in bioRxiv.
Building their study based on the previously reported work that discovered smokers are highly susceptible to SARS-CoV-2 and are more likely to require aggressive clinical interventions in a study of 1,099 patients with laboratory-confirmed COVID-19, 12.3% of current smokers required ventilation, were admitted to ICU or died compared to only 4.7% non-smokers. Jason M. Sheltzer who is the corresponding author and his collaborator Joan C. Smith from Google, investigated the underlaying causes of these differences in clinical outcome through the use of gene expression datasets (specifically RNA-Seq and scRNA-Seq) obtained from Gene Expression Omnibus (GEO), a publicly available repository for gene expression data, to particularly identify factors that influence susceptibility to SARS-CoV-2 infection.
The researchers also observed that age and gender were the factors compared with ACE2 expression and was found that ACE2 expression levels are unaffected or influenced by gender or age. However, since age and gender are the risk factors for SARS-CoV-2 infections, Sheltzer and his colleague investigated whether age or gender was associated with increased in ACE2 expression. They assessed the ACE2 expression from two different human cohorts of lung tissues obtained from Genotype-Tissue Expression project (GTEx) and organ donors.
Comparing the expression of ACE2 between men and women and between young ((<29 years) and elderly ((>70 years) individuals find no differences, and thus concluded that the rate of men and older patients dying from COVID-19 is not related to differences in ACE2 expression in their respiratory tract. “In total, these findings suggest that the increased morbidity of men and older patients with COVID-19 is unlikely to result from inherent differences in ACE2 expression in the respiratory tract” says the authors.
They further investigated whether cigarette smoking could increase the presence of ACE2 in human lung tissue by analysing the three cohorts of current smokers and never or non-smokers. Sheltzer and his colleague discovered that smokers' lung tissue expressed 40% more of ACE2 compared to lung tissue of non-smokers. Thus, the researcher said “Our results demonstrate that exposure to cigarette smoke increases the expression of the coronavirus receptor ACE2 in human respiratory tissue, and this upregulation is potentially reversible."
Although, they mentioned that the cause or factors that mediate susceptibility to SARS-CoV-2 infections are not completely understood. However, “we speculate that the increased expression of ACE2 in the lungs of smokers could partially contribute to the severe cases of COVID-19 that have been observed in this population”, says the researchers.
Thus, recommending that cessation in smoking could lessen the risks that is link with SARS-CoV-2 infections that cause COVID-19. Therefore, it is advisable for the smokers to gradually withdraw from cigarette smoking to reduce the high risk of contracting SARS- CoV-2 infections especially during this COVID-19 pandemic.
Umar Ahmad is a PhD student of Genetics with Genetics and Regenerative Medicine Research Centre (GRMRC) of the Universiti Putra Malaysia(UPM) and the Malaysia Genome Institute (MGI), studying transcriptomic misregulation in bladder cancer. He can be found on Twitter @babasaraki01.
1. Fan Z, Wu G, Yue M, Ye J, Chen Y, Xu B, et al. Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism. Life sciences 2019;
2. Xu X, Shi L, Ma X, Su H, Ma G, Wu X, et al. RhoA-Rho associated kinase signaling leads to renin-angiotensin system imbalance and angiotensin converting enzyme 2 has a protective role in acute pulmonary embolism. Thromb. Res. 2019;176:85–94.
3. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 2020;5:562–9.
4. Smith JC, Sheltzer JM. Cigarette smoke triggers the expansion of a subpopulation of respiratory epithelial cells that express the SARS-CoV-2 receptor ACE2. BioRxiv 2020;
5. Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;
6. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30:207–10.
7. GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 2013;45:580–5.
8. Carithers LJ, Ardlie K, Barcus M, Branton PA, Britton A, Buia SA, et al. A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project. Biopreserv. Biobank. 2015;13:311–9.
9. Gruber MP, Coldren CD, Woolum MD, Cosgrove GP, Zeng C, Barón AE, et al. Human lung project: evaluating variance of gene expression in the human lung. Am. J. Respir. Cell Mol. Biol. 2006;35:65–71.