{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:17:57Z","timestamp":1777450677039,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The epicenter of the original outbreak in China has high male smoking rates of around 50%, and early reported death rates have an emphasis on older males, therefore the likelihood of smokers being overrepresented in fatalities is high. In Iran, China, Italy, and South Korea, female smoking rates are much lower than males. Fewer females have contracted the virus. If this analysis is correct, then Indonesia would be expected to begin experiencing high rates of Covid-19 because its male smoking rate is over 60% (Tobacco Atlas). Smokers are vulnerable to respiratory viruses. Smoking can upregulate angiotensin-converting enzyme-2 (ACE2) receptor, the known receptor for both the severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV) and the human respiratory coronavirus NL638. This could also be true for new electronic smoking devices such as electronic cigarettes and \u201cheat-not-burn\u201d IQOS devices. ACE2 could be a novel adhesion molecule for SARS-CoV-2 causing Covid-19 and a potential therapeutic target for the prevention of fatal microbial infections, and therefore it should be fast tracked and prioritized for research and investigation. Data on smoking status should be collected on all identified cases of Covid-19.<\/jats:p>","DOI":"10.3390\/jcm9030841","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T07:29:07Z","timestamp":1584689347000},"page":"841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":377,"title":["Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19)"],"prefix":"10.3390","volume":"9","author":[{"given":"Samuel James","family":"Brake","sequence":"first","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania 7248, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Barnsley","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Tasmania, Hobart, Tasmania 7001, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-2276","authenticated-orcid":false,"given":"Wenying","family":"Lu","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania 7248, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kielan Darcy","family":"McAlinden","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania 7248, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0570-7059","authenticated-orcid":false,"given":"Mathew Suji","family":"Eapen","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania 7248, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukhwinder Singh","family":"Sohal","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania 7248, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1042\/CS20181009","article-title":"New therapeutic targets for the prevention of infectious acute exacerbations of COPD: Role of epithelial adhesion molecules and inflammatory pathways","volume":"133","author":"Atto","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1164\/rccm.201808-1553LE","article-title":"Dysfunctional Immunity and Microbial Adhesion Molecules in Smoking-Induced Pneumonia","volume":"199","author":"Eapen","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1901641","DOI":"10.1183\/13993003.01641-2019","article-title":"Mitochondrial dysfunction in macrophages: A key to defective bacterial phagocytosis in COPD","volume":"54","author":"Eapen","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1042\/CS20171261","article-title":"Understanding novel mechanisms of microbial pathogenesis in chronic lung disease: Implications for new therapeutic targets","volume":"132","author":"Eapen","year":"2018","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1702257","DOI":"10.1183\/13993003.02257-2017","article-title":"Inhaled corticosteroids and increased microbial load in COPD: Potential role of epithelial adhesion molecules","volume":"51","author":"Sohal","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jinf.2019.08.014","article-title":"Cigarette smoking and the occurrence of influenza\u2014Systematic review","volume":"79","author":"Lawrence","year":"2019","journal-title":"J. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/EDE.0000000000000984","article-title":"Smoking and Influenza-associated Morbidity and Mortality: A Systematic Review and Meta-analysis","volume":"30","author":"Han","year":"2019","journal-title":"Epidemiology"},{"key":"ref_8","unstructured":"World Health Organisation (2020, March 11). Chronic Obstructive Pulmonary Disease (COPD). Available online: https:\/\/www.who.int\/respiratory\/copd\/en\/."},{"key":"ref_9","first-page":"2689","article-title":"It takes two to tango: Cigarette smoke partners with viruses to promote emphysema","volume":"118","author":"Tuder","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_10","unstructured":"World Health Organisation (2020, March 05). Coronavirus Disease (COVID-19) Outbreak. Available online: https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zheng, Y.Y., Ma, Y.T., Zhang, J.Y., and Xie, X. (2020). COVID-19 and the cardiovascular system. Nat. Rev. Cardiol.","DOI":"10.1038\/s41569-020-0360-5"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1093\/ntr\/ntw016","article-title":"Comorbidities Workgroup of the Society for Research on Nicotine and Tobacco (SRNT) Treatment Network. Exploring Issues of Comorbid Conditions in People Who Smoke","volume":"18","author":"Rojewski","year":"2016","journal-title":"Nicotine Tob. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1177\/0733464817716967","article-title":"Trends in Cigarette Smoking Among Older Male Adults in China: An Urban-Rural Comparison","volume":"38","author":"Zhi","year":"2019","journal-title":"J. Appl. Gerontol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sun, K., Chen, J., and Viboud, C. (2020). Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: A population-level observational study. Lancet Digit. Health.","DOI":"10.1016\/S2589-7500(20)30026-1"},{"key":"ref_15","unstructured":"Roser, M., Ritchie, H., and Ortiz-Ospina, E. (2020, March 13). Coronavirus Disease (COVID-19)\u2014Research and Statistics. Available online: https:\/\/ourworldindata.org\/coronavirus."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1126\/science.1116480","article-title":"Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor","volume":"309","author":"Li","year":"2005","journal-title":"Science (N.Y.)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104742","DOI":"10.1016\/j.antiviral.2020.104742","article-title":"The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade","volume":"176","author":"Coutard","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.virol.2006.02.003","article-title":"Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry","volume":"350","author":"Follis","year":"2006","journal-title":"Virology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbapap.2011.07.001","article-title":"Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure","volume":"1824","author":"Kido","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","unstructured":"NCBI (2020, March 11). ACE2 Angiotensin I Converting Enzyme 2 [Homo Sapiens (Human)] Gene ID: 59272, Updated on 5-Mar-2020, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/59272."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1001\/jamainternmed.2017.1419","article-title":"Heat-Not-Burn Tobacco Cigarettes: Smoke by Any Other Name","volume":"177","author":"Auer","year":"2017","journal-title":"JAMA Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jmv.25682","article-title":"Cross-species transmission of the newly identified coronavirus 2019-nCoV","volume":"92","author":"Ji","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_25","unstructured":"World Health Organisation (2020, March 11). SARS (Severe Acute Respiratory Syndrome). Available online: https:\/\/www.who.int\/ith\/diseases\/sars\/en\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.1073\/pnas.0409465102","article-title":"Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry","volume":"102","author":"Hofmann","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11427-020-1637-5","article-title":"Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission","volume":"63","author":"Xu","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_28","unstructured":"National Institutes of Health, U.S., and Department of Health and Human Services (2020, March 11). Novel Coronavirus Structure Reveals Targets for Vaccines and Treatments, Available online: www.nih.gov\/news-events\/nih-research-matters\/novel-coronavirus-structure-reveals-targets-vaccines-treatments."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wrapp, D., Wang, N., Corbett, K.S., Goldsmith, J.A., Hsieh, C.l., Abiona, O., Graham, B.S., and McLellan, J.S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (N.Y.).","DOI":"10.1101\/2020.02.11.944462"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zhao, Z., Wang, Y., Zhou, Y., Ma, Y., and Zuo, W. (2020). Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv, bioRxiv:2020.01.26.919985.","DOI":"10.1101\/2020.01.26.919985"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.chest.2017.05.024","article-title":"Potential Mechanisms of Microbial Pathogens in Idiopathic Interstitial Lung Disease","volume":"152","author":"Sohal","year":"2017","journal-title":"Chest"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus\u2013induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature03712","article-title":"Angiotensin-converting enzyme 2 protects from severe acute lung failure","volume":"436","author":"Imai","year":"2005","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, J., Lou, Q., Chen, R., Chen, T., and Li, J. (2020). Susceptibility Analysis of COVID-19 in Smokers Based on ACE2. Preprints.","DOI":"10.20944\/preprints202003.0078.v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9638","DOI":"10.3390\/ijerph110909638","article-title":"Effect of shisha (waterpipe) smoking on lung functions and fractional exhaled nitric oxide (FeNO) among Saudi young adult shisha smokers","volume":"11","author":"Meo","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"00159","DOI":"10.1183\/23120541.00159-2018","article-title":"IQOS exposure impairs human airway cell homeostasis: Direct comparison with traditional cigarette and e-cigarette","volume":"5","author":"Sohal","year":"2019","journal-title":"ERJ Open Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Miyashita, L., Suri, R., Dearing, E., Mudway, I., Dove, R.E., Neill, D.R., Zyl-Smit, R.V., Kadioglu, A., and Grigg, J. (2018). E-cigarette vapour enhances pneumococcal adherence to airway epithelial cells. Eur. Respir. J., 51.","DOI":"10.1183\/13993003.01592-2017"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"00114-2019","DOI":"10.1183\/23120541.00114-2019","article-title":"There can be smoke without fire: Warranted caution in promoting electronic cigarettes and heat not burn devices as a safer alternative to cigarette smoking","volume":"5","author":"McAlinden","year":"2019","journal-title":"ERJ Open Res."},{"key":"ref_40","unstructured":"Layne, N. (2020, March 10). Smoking or Vaping Increases Risks for Those with Coronavirus: NYC Mayor. Available online: https:\/\/www.reuters.com\/article\/us-health-coronavirus-usa-vaping-idUSKBN20V0Z0."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/3\/841\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:09:55Z","timestamp":1760173795000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/3\/841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,20]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["jcm9030841"],"URL":"https:\/\/doi.org\/10.3390\/jcm9030841","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,20]]}}}