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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

Expression and Clinical Significance of SARS-CoV-2 Human Targets in Neoplastic and Non-Neoplastic Lung Tissues

Author(s): Karthikeyan Subbarayan, Kamatchi Ulagappan, Claudia Wickenhauser and Barbara Seliger*

Volume 21, Issue 5, 2021

Published on: 07 December, 2020

Page: [428 - 442] Pages: 15

DOI: 10.2174/1568009620666201207145019

Price: $65


Background: A higher incidence of COVID-19 infection was demonstrated in cancer patients, including lung cancer patients. This study was conducted to get insights into the enhanced frequency of COVID-19 infection in cancer.

Methods: Using different bioinformatics tools, the expression and methylation patterns of ACE2 and TMPRSS2 were analyzed in healthy and malignant tissues, focusing on lung adenocarcinoma and data were correlated to clinical parameters and smoking history.

Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression levels in digestive, urinary and reproductive organs, while the overall analysis of 72 paired tissues demonstrated significantly lower expression levels of ACE2 in cancer tissues when compared to normal counterparts. In contrast, ACE2, but not TMPRSS2, was overexpressed in LUAD, which inversely correlated to the promoter methylation. This upregulation of ACE2 was age-dependent in LUAD, but not in normal lung tissues. TMPRSS2 expression in non-neoplastic lung tissues was heterogeneous and dependent on sex and smoking history, while it was downregulated in LUAD of smokers. Cancer progression was associated with a decreased TMPRSS2 but unaltered ACE2. In contrast, ACE2 and TMPRSS2 of lung metastases derived from different cancer subtypes was higher than organ metastases of other sites. TMPRSS2, but not ACE2, was associated with LUAD patients’ survival.

Conclusions: Comprehensive molecular analyses revealed a heterogeneous and distinct expression and/or methylation profile of ACE2 and TMPRSS2 in healthy lung vs. LUAD tissues across sex, age and smoking history and might have implications for COVID-19 disease.

Keywords: COVID-19, metastasis, lung adenocarcinoma, ACE2, TMPRSS2, clinical relevance.

Graphical Abstract
Liu, J.; Zheng, X.; Tong, Q.; Li, W.; Wang, B.; Sutter, K.; Trilling, M.; Lu, M.; Dittmer, U.; Yang, D. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J. Med. Virol., 2020, 92(5), 491-494.
[] [PMID: 32056249]
Kahn, J.S.; McIntosh, K. History and recent advances in coronavirus discovery. Pediatr. Infect. Dis. J., 2005, 24(11)(Suppl.), S223-S227.
[] [PMID: 16378050]
Paules, C.I.; Marston, H.D.; Fauci, A.S. coronavirus infections- more than just the common cold. JAMA, 2020, 323(8), 707-708.
[] [PMID: 31971553]
Drosten, C. Is MERS another SARS? Lancet Infect. Dis., 2013, 13(9), 727-728.
[] [PMID: 23891403]
Momattin, H.; Mohammed, K.; Zumla, A.; Memish, Z.A.; Al-Tawfiq, J.A. Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)- possible lessons from a systematic review of SARS-CoV therapy. Int. J. Infect. Dis., 2013, 17(10), e792-e798.
[] [PMID: 23993766]
Adams, M.J.; Carstens, E.B. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2012). Arch. Virol., 2012, 157(7), 1411-1422.
[] [PMID: 22481600]
Paraskevis, D.; Kostaki, E.G.; Magiorkinis, G.; Panayiotakopoulos, G.; Sourvinos, G.; Tsiodras, S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect. Genet. Evol., 2020, 79
[] [PMID: 32004758]
Guan, W.J.; Ni, Z.Y.; Hu, Y.; Liang, W.H.; Ou, C.Q.; He, J.X.; Liu, L.; Shan, H.; Lei, C.L.; Hui, D.S.C.; Du, B.; Li, L.J.; Zeng, G.; Yuen, K.Y.; Chen, R.C.; Tang, C.L.; Wang, T.; Chen, P.Y.; Xiang, J.; Li, S.Y.; Wang, J.L.; Liang, Z.J.; Peng, Y.X.; Wei, L.; Liu, Y.; Hu, Y.H.; Peng, P.; Wang, J.M.; Liu, J.Y.; Chen, Z.; Li, G.; Zheng, Z.J.; Qiu, S.Q.; Luo, J.; Ye, C.J.; Zhu, S.Y.; Zhong, N.S. China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med., 2020, 382(18), 1708-1720.
[] [PMID: 32109013]
Li, Q.; Guan, X.; Wu, P.; Wang, X.; Zhou, L.; Tong, Y.; Ren, R.; Leung, K.S.M.; Lau, E.H.Y.; Wong, J.Y.; Xing, X.; Xiang, N.; Wu, Y.; Li, C.; Chen, Q.; Li, D.; Liu, T.; Zhao, J.; Liu, M.; Tu, W.; Chen, C.; Jin, L.; Yang, R.; Wang, Q.; Zhou, S.; Wang, R.; Liu, H.; Luo, Y.; Liu, Y.; Shao, G.; Li, H.; Tao, Z.; Yang, Y.; Deng, Z.; Liu, B.; Ma, Z.; Zhang, Y.; Shi, G.; Lam, T.T.Y.; Wu, J.T.; Gao, G.F.; Cowling, B.J.; Yang, B.; Leung, G.M.; Feng, Z. Early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia. N. Engl. J. Med., 2020, 382(13), 1199-1207.
[] [PMID: 31995857]
Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; Xia, J.; Yu, T.; Zhang, X.; Zhang, L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(10223), 507-513.
[] [PMID: 32007143]
Kruse, R.L. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000 Res., 2020, 9, 72.
[] [PMID: 32117569]
Chan, J.F.; Yuan, S.; Kok, K.H.; To, K.K.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C.C.; Poon, R.W.; Tsoi, H.W.; Lo, S.K.; Chan, K.H.; Poon, V.K.; Chan, W.M.; Ip, J.D.; Cai, J.P.; Cheng, V.C.; Chen, H.; Hui, C.K.; Yuen, K.Y. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet, 2020, 395(10223), 514-523.
[] [PMID: 31986261]
Wang, C.; Horby, P.W.; Hayden, F.G.; Gao, G.F. A novel coronavirus outbreak of global health concern. Lancet, 2020, 395(10223), 470-473.
[] [PMID: 31986257]
Fung, T.S.; Liu, D.X. Human coronavirus: host-pathogen interaction. Annu. Rev. Microbiol., 2019, 73, 529-557.
[] [PMID: 31226023]
Menter, T.; Haslbauer, J.D.; Nienhold, R.; Savic, S.; Hopfer, H.; Deigendesch, N.; Frank, S.; Turek, D.; Willi, N.; Pargger, H.; Bassetti, S.; Leuppi, J.D.; Cathomas, G.; Tolnay, M.; Mertz, K.D.; Tzankov, A. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology, 2020.
[] [PMID: 32364264]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Kruger, N.; Herrler, T.; Erichsen, S.; Schiergens, T. S.; Herrler, G.; Wu, N. H.; Nitsche, A.; Muller, M. A.; Drosten, C.; Pohlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor Cell, 2020, 181(2), 271-280.
Zhou, Y.; Vedantham, P.; Lu, K.; Agudelo, J.; Carrion, R., Jr; Nunneley, J.W.; Barnard, D.; Pöhlmann, S.; McKerrow, J.H.; Renslo, A.R.; Simmons, G. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res., 2015, 116, 76-84.
[] [PMID: 25666761]
Simmons, G.; Zmora, P.; Gierer, S.; Heurich, A.; Pöhlmann, S. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res., 2013, 100(3), 605-614.
[] [PMID: 24121034]
Xia, Y.; Jin, R.; Zhao, J.; Li, W.; Shen, H. Risk of COVID-19 for patients with cancer. Lancet Oncol., 2020, 21(4), e180.
[] [PMID: 32142622]
Sidaway, P. COVID-19 and cancer: what we know so far. Nat. Rev. Clin. Oncol., 2020, 17(6), 336.
[] [PMID: 32265531]
Desai, A.; Sachdeva, S.; Parekh, T.; Desai, R. COVID-19 and cancer: lessons from a pooled meta-analysis. JCO Glob Oncol, 2020, 6, 557-559.
[] [PMID: 32250659]
Liang, W.; Guan, W.; Chen, R.; Wang, W.; Li, J.; Xu, K.; Li, C.; Ai, Q.; Lu, W.; Liang, H.; Li, S.; He, J. Cancer patients in SARS- CoV-2 infection: a nationwide analysis in China. Lancet Oncol., 2020, 21(3), 335-337.
[] [PMID: 32066541]
Yu, J.; Ouyang, W.; Chua, M. L. K.; Xie, C. SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China. JAMA Oncol, 2020.
Dai, M.; Liu, D.; Liu, M.; Zhou, F.; Li, G.; Chen, Z.; Zhang, Z.; You, H.; Wu, M.; Zheng, Q.; Xiong, Y.; Xiong, H.; Wang, C.; Chen, C.; Xiong, F.; Zhang, Y.; Peng, Y.; Ge, S.; Zhen, B.; Yu, T.; Wang, L.; Wang, H.; Liu, Y.; Chen, Y.; Mei, J.; Gao, X.; Li, Z.; Gan, L.; He, C.; Li, Z.; Shi, Y.; Qi, Y.; Yang, J.; Tenen, D.G.; Chai, L.; Mucci, L.A.; Santillana, M.; Cai, H. Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak. Cancer Discov., 2020, 10(6), 783-791.
[PMID: 32345594]
Peng, L.; Zagorac, S.; Stebbing, J. Managing patients with cancer in the COVID-19 era. Eur. J. Cancer, 2020, 132, 5-7.
[] [PMID: 32302754]
Cai, H. Sex difference and smoking predisposition in patients with COVID-19. Lancet Respir. Med., 2020, 8(4), e20.
[] [PMID: 32171067]
Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med., 2020, 14(2), 185-192.
[] [PMID: 32170560]
Lukassen, S.; Chua, R.L.; Trefzer, T.; Kahn, N.C.; Schneider, M.A.; Muley, T.; Winter, H.; Meister, M.; Veith, C.; Boots, A.W.; Hennig, B.P.; Kreuter, M.; Conrad, C.; Eils, R. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J., 2020, 39(10)
[] [PMID: 32246845]
Cheng, Q.; Zhou, L.; Zhou, J.; Wan, H.; Li, Q.; Feng, Y. ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC. Oncol. Rep., 2016, 36(3), 1403-1410.
[] [PMID: 27460845]
Feng, Y.; Ni, L.; Wan, H.; Fan, L.; Fei, X.; Ma, Q.; Gao, B.; Xiang, Y.; Che, J.; Li, Q. Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro. Oncol. Rep., 2011, 26(5), 1157-1164.
[PMID: 21769437]
Zhang, H.; Quek, K.; Chen, R.; Chen, J.; Chen, B. Expression of the SAR2-Cov-2 receptor ACE2 reveals the susceptibility of COVID-19 in non-small cell lung cancer. J. Cancer, 2020, 11(18), 5289-5292.
[] [PMID: 32742475]
Chai, P.; Yu, J.; Ge, S.; Jia, R.; Fan, X. Genetic alteration, RNA expression, and DNA methylation profiling of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignancies: a pan-cancer analysis. J. Hematol. Oncol., 2020, 13(1), 43.
[] [PMID: 32366279]
Kong, Q.; Xiang, Z.; Wu, Y.; Gu, Y.; Guo, J.; Geng, F. Analysis of the susceptibility of lung cancer patients to SARS-CoV-2 infection. Mol. Cancer, 2020, 19(1), 80.
[] [PMID: 32345328]
Park, S.J.; Yoon, B.H.; Kim, S.K.; Kim, S.Y. GENT2: an updated gene expression database for normal and tumor tissues. BMC Med. Genomics, 2019, 12(Suppl. 5), 101.
[] [PMID: 31296229]
Cerami, E.; Gao, J.; Dogrusoz, U.; Gross, B.E.; Sumer, S.O.; Aksoy, B.A.; Jacobsen, A.; Byrne, C.J.; Heuer, M.L.; Larsson, E.; Antipin, Y.; Reva, B.; Goldberg, A.P.; Sander, C.; Schultz, N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov., 2012, 2(5), 401-404.
[] [PMID: 22588877]
Gao, J.; Aksoy, B.A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S.O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; Cerami, E.; Sander, C.; Schultz, N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal., 2013, 6(269), pl1.
[] [PMID: 23550210]
Shi, J.; Marconett, C.N.; Duan, J.; Hyland, P.L.; Li, P.; Wang, Z.; Wheeler, W.; Zhou, B.; Campan, M.; Lee, D.S.; Huang, J.; Zhou, W.; Triche, T.; Amundadottir, L.; Warner, A.; Hutchinson, A.; Chen, P.H.; Chung, B.S.; Pesatori, A.C.; Consonni, D.; Bertazzi, P.A.; Bergen, A.W.; Freedman, M.; Siegmund, K.D.; Berman, B.P.; Borok, Z.; Chatterjee, N.; Tucker, M.A.; Caporaso, N.E.; Chanock, S.J.; Laird-Offringa, I.A.; Landi, M.T. Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue. Nat. Commun., 2014, 5, 3365.
[] [PMID: 24572595]
Bhandari, V.; Hoey, C.; Liu, L.Y.; Lalonde, E.; Ray, J.; Livingstone, J.; Lesurf, R.; Shiah, Y.J.; Vujcic, T.; Huang, X.; Espiritu, S.M.G.; Heisler, L.E.; Yousif, F.; Huang, V.; Yamaguchi, T.N.; Yao, C.Q.; Sabelnykova, V.Y.; Fraser, M.; Chua, M.L.K.; van der Kwast, T.; Liu, S.K.; Boutros, P.C.; Bristow, R.G. Molecular landmarks of tumor hypoxia across cancer types. Nat. Genet., 2019, 51(2), 308-318.
[] [PMID: 30643250]
Ellrott, K.; Bailey, M. H.; Saksena, G.; Covington, K. R.; Kandoth, C.; Stewart, C.; Hess, J.; Ma, S.; Chiotti, K. E.; McLellan, M.; Sofia, H. J.; Hutter, C.; Getz, G.; Wheeler, D.; Ding, L.; Group, M. C. W. Cancer Genome Atlas Research, N., Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines. Cell Syst, 2018, 6(3), 271-281.
Gao, Q.; Liang, W. W.; Foltz, S. M.; Mutharasu, G.; Jayasinghe, R. G.; Cao, S.; Liao, W. W.; Reynolds, S. M.; Wyczalkowski, M. A.; Yao, L.; Yu, L.; Sun, S. Q.; Fusion Analysis Working, G.; Chen, K; Lazar, A.J; Fields, R.C; Wendl, M.C; Van Tine, B.A; Vij, R.; Chen, F.; Nykter, M.; Shmulevich, I; Ding, L. Cancer genome atlas research, n.driver fusions and their implications in the development and treatment of human cancers Cell Rep, 2018, 23(1), 227-238.
Hoadley, K. A.; Yau, C.; Hinoue, T.; Wolf, D. M.; Lazar, A. J.; Drill, E.; Shen, R.; Taylor, A. M.; Cherniack, A. D.; Thorsson, V.; Akbani, R.; Bowlby, R.; Wong, C. K.; Wiznerowicz, M.; Sanchez-Vega, F.; Robertson, A. G.; Schneider, B. G.; Lawrence, M. S.; Noushmehr, H.; Malta, T. M.; Cancer Genome Atlas, N.; Stuart, J. M.; Benz, C. C.; Laird, P. W. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer Cell, 2018, 173(2), 291-304.
Liu, J.; Lichtenberg, T.; Hoadley, K. A.; Poisson, L. M.; Lazar, A. J.; Cherniack, A. D.; Kovatich, A. J.; Benz, C. C.; Levine, D. A.; Lee, A. V.; Omberg, L.; Wolf, D. M.; Shriver, C. D.; Thorsson, V.; Hu, H. Cancer genome atlas research, integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics Cell , 2018, 173(2), 400-416.
Sanchez-Vega, F.; Mina, M.; Armenia, J.; Chatila, W. K.; Luna, A.; La, K. C.; Dimitriadoy, S.; Liu, D. L.; Kantheti, H. S.; Saghafinia, S.; Chakravarty, D.; Daian, F.; Gao, Q.; Bailey, M. H.; Liang, W. W.; Foltz, S. M.; Shmulevich, I.; Ding, L.; Heins, Z.; Ochoa, A.; Gross, B.; Gao, J.; Zhang, H.; Kundra, R.; Kandoth, C.; Bahceci, I.; Dervishi, L.; Dogrusoz, U.; Zhou, W.; Shen, H.; Laird, P. W.; Way, G. P.; Greene, C. S.; Liang, H.; Xiao, Y.; Wang, C.; Iavarone, A.; Berger, A. H.; Bivona, T. G.; Lazar, A. J.; Hammer, G. D.; Giordano, T.; Kwong, L. N.; McArthur, G.; Huang, C.; Tward, A. D.; Frederick, M. J.; McCormick, F.; Meyerson, M. Oncogenic signaling pathways in the cancer genome atlas Cell, 2018, 173(2), 321-337.
Taylor, A. M.; Shih, J.; Ha, G.; Gao, G. F.; Zhang, X.; Berger, A. C.; Schumacher, S. E.; Wang, C.; Hu, H.; Liu, J.; Lazar, A. J.; Cherniack, A. D.; Beroukhim, R.; Meyerson, M. Cancer Genome Atlas Research, N.Genomic and Functional Approaches to Understanding Cancer Aneuploidy Cancer Cell, 2018, 33(4), 676-6989.
Cai, L.; Lin, S.; Girard, L.; Zhou, Y.; Yang, L.; Ci, B.; Zhou, Q.; Luo, D.; Yao, B.; Tang, H.; Allen, J.; Huffman, K.; Gazdar, A.; Heymach, J.; Wistuba, I.; Xiao, G.; Minna, J.; Xie, Y. LCE: an open web portal to explore gene expression and clinical associations in lung cancer. Oncogene, 2019, 38(14), 2551-2564.
[] [PMID: 30532070]
Chandrashekar, D.S.; Bashel, B.; Balasubramanya, S.A.H.; Creighton, C.J.; Ponce-Rodriguez, I.; Chakravarthi, B.V.S.K.; Varambally, S. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8), 649-658.
[] [PMID: 28732212]
Zheng, G.; Ma, Y.; Zou, Y.; Yin, A.; Li, W.; Dong, D. HCMDB: the human cancer metastasis database. Nucleic Acids Res., 2018, 46(D1), D950-D955.
[] [PMID: 29088455]
Okayama, H.; Kohno, T.; Ishii, Y.; Shimada, Y.; Shiraishi, K.; Iwakawa, R.; Furuta, K.; Tsuta, K.; Shibata, T.; Yamamoto, S.; Watanabe, S.; Sakamoto, H.; Kumamoto, K.; Takenoshita, S.; Gotoh, N.; Mizuno, H.; Sarai, A.; Kawano, S.; Yamaguchi, R.; Miyano, S.; Yokota, J. Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res., 2012, 72(1), 100-111.
[] [PMID: 22080568]
Gebhard, C.; Regitz-Zagrosek, V.; Neuhauser, H.K.; Morgan, R.; Klein, S.L. Impact of sex and gender on COVID-19 outcomes in Europe. Biol. Sex Differ., 2020, 11(1), 29.
[] [PMID: 32450906]
Zhang, L.; Zhu, F.; Xie, L.; Wang, C.; Wang, J.; Chen, R.; Jia, P.; Guan, H. Q.; Peng, L.; Chen, Y.; Peng, P.; Zhang, P.; Chu, Q.; Shen, Q.; Wang, Y.; Xu, S. Y.; Zhao, J. P.; Zhou, M. Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Ann Oncol, 2020.
Zhang, H.; Xie, C.; Huang, Y. Treatment and outcome of a patient with lung cancer infected with severe acute respiratory syndrome coronavirus-2. J. Thorac. Oncol., 2020, 15(5), e63-e64.
[] [PMID: 32147577]
Yang, X.; Tan, B.; Zhou, X.; Xue, J.; Zhang, X.; Wang, P.; Shao, C.; Li, Y.; Li, C.; Xia, H.; Qiu, J. Interferon-inducible transmembrane protein 3 genetic variant rs12252 and influenza susceptibility and severity: a meta-analysis. PLoS One, 2015, 10(5)
[] [PMID: 25942469]
Li, M.Y.; Li, L.; Zhang, Y.; Wang, X.S. Expression of the SARS- CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis. Poverty, 2020, 9(1), 45.
[] [PMID: 32345362]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273.
[] [PMID: 32015507]
Li, G.; He, X.; Zhang, L.; Ran, Q.; Wang, J.; Xiong, A.; Wu, D.; Chen, F.; Sun, J.; Chang, C. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J. Autoimmun., 2020, 112
[] [PMID: 32303424]
Qian, Y.R.; Guo, Y.; Wan, H.Y.; Fan, L.; Feng, Y.; Ni, L.; Xiang, Y.; Li, Q.Y. Angiotensin-converting enzyme 2 attenuates the metastasis of non-small cell lung cancer through inhibition of epithelial-mesenchymal transition. Oncol. Rep., 2013, 29(6), 2408-2414.
[] [PMID: 23545945]
Stebbing, J.; Atkins, M.; Nelson, M.; Rajpopat, S.; Newsom- Davis, T.; Gazzard, B.; Bower, M. Hepatitis B reactivation during combination chemotherapy for AIDS-related lymphoma is uncommon and does not adversely affect outcome. Blood, 2004, 103(6), 2431-2432.
[] [PMID: 14998920]
Shang, L.; Zhao, J.; Hu, Y.; Du, R.; Cao, B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet, 2020, 395(10225), 683-684.
[] [PMID: 32122468]
Russell, C.D.; Millar, J.E.; Baillie, J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet, 2020, 395(10223), 473-475.
[] [PMID: 32043983]
Farsalinos, K.; Barbouni, A.; Niaura, R. Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option? Intern. Emerg. Med., 2020.

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