Covid-19 And Co-Infections: An Overview Of Ace2 Mediated Viral Entry Of Sars-Cov-2 And Multiorgan Failure In Covid-19
Keywords:COVID-19, co-infections, ACE2 receptor, SARS-Cov-2, multi organs
COVID-19 is highly fatal disease having high mortality rate and is declared as pandemic situation by world health organization. It shows a clear indication that every individual is at risk of this pandemic especially older individual and immunocompromised persons. As its casual agent is SARS-Cov-2 and the main target site of this virus is the ACE2 receptor of lungs. But as compared to lungs ACE2 receptor is highly expressed in other organs i.e. kidney, liver, brain, GI tract, cutaneous, adipose tissues and cardiovascular system these organs are susceptible to COVID-19 infections because of having ACE2 receptor. Many co-infections associated with COVID-19 are reported i.e. neurological manifestation of COVID-19, cutaneous manifestations of COVID-19, endothelial cell infection and endotheliitis, adipose tissues infections, cerebral hemorrhage, liver injury, cardiovascular complications, kidney infection, trigger immune system response and subsequent organ failure. In this review we highlight ACE2 mediated viral entry of the SARS-Cov-2 and subsequent multi organ failure in COVID-19.
C.I. Paules, H.D. Marston, A.S. Fauci, Coronavirus infections – more than just the common cold, JAMA (2020) Epub ahead of print.
J. Yang, Y. Zheng, X. Gou, et al., Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis, Int. J. Infect. Dis. (2020) Epub ahead of print.
D. Wang, B. Hu, C. Hu, et al., Clinical characteristics of 138 hospitalized patients with novel coronavirus-infected pneumonia in Wuhan, China, JAMA (2020) Epub ahead of print.
Xu X, Chen P, Wang J, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020;63:457–60. https://doi.org/10.1007/s11427-020-1637-5.
Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv. 2020. https://doi. org/10.1101/2020.01.26.919985.
Ding Y, He L, Zhang Q, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 2004;203:622–30. https://doi.org/ 10.1002/path.1560.
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–7. https://doi.org/ 10.1002/path.1570.
J. R. Lechien, C. M. Chiesa Estomba, D. R. De Siati, et al., Olfactory and gustatory dysfunctions as a clinical presentation of mild to moderate forms of the coronavirus disease (COVID 19): A multicenter European study, European Archives of Oto-Rhino-Laryngology (2020) Published online April 2, 2020.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–62.
Horton R. Offline: COVID-19—bewilderment and candour. Lancet 2020; 395: 1178
P. Zhai, Y. Ding, X. Wu, J. Long, Y. Zhong, Y. Li, The epidemiology, diagnosis and treatment of COVID-19, Int. J. Antimicrob. Agents 28 (March) (2020) 105955, doi:http://dx.doi.org/10.1016/j.ijantimicag.2020.105955 [Epub ahead of print].
R. Gianotti, P. Zerbi, R. Dodiuk-Gad, Histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy, J. Cosmet. Dermatol. Sci. Appl. (2020) In press
F.A. Klok, M.J.H.A. Kruip, N.J.M. van der Meer, M.S. Arbous, D.A.M.P.J. Gommers, K.M. Kant, F.H.J. Kaptein, J. van Paassen, M.A.M. Stals, M.V. Huisfman, H. Endeman, Incidence of thrombotic complications in critically ill ICU patients with COVID-19, Thromb. Res. (2020), https://doi.org/10.1016/j.thromres.2020. 04.013
Abdulkadir, T. U. N. Ç., ÜNLÜBAŞ, Y., ALEMDAR, M., & AKYÜZ, E. (2020). Coexistence of Covid-19 and Acute Ischemic Stroke Report of Four Cases. Journal of Clinical Neuroscience.
Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The Novel Coronavirus 2019 epidemic and kidneys [published online ahead of print, 2020 Mar 7]. Kidney Int 2020. https://doi.org/10.1016/j.kint.2020.03.001.
WHO. Coronavirus-19 (COVID-19) situation report—82. 2020. Available at: https:// www.who.int/docs/default-source/coronaviruse/situation-reports/20200411-sitrep82-covid-19.pdf?sfvrsn=74a5d15_2. Assessed April 12, 2020.
Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199–207. https://doi.org/ 10.1056/NEJMoa2001316.
Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro Surveill 2020;25:2000062. https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000062. ARTICLE IN PRESS CurrProblCardiol, 00 2020 15
Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: what we know [published online ahead of print, 2020 Mar 11]. Int J Infect Dis 2020. https://doi.org/10.1016/j. ijid.2020.03.004.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention [published online ahead of print, 2020 Feb 24]. JAMA 2020. https://doi.org/10.1001/jama.2020.2648.
Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet 2020;395:1014–5. https://doi.org/10.1016/S0140-6736(20)30633-4.
Update on the prevalence and control of novel coronavirus-induced pneumonia as of 24:00 on February 21. http://www.nhc.gov.cn/xcs/yqtb/202002/543cc50897 8a48d2b9322bdc83daa6fd.shtml (accessed February 23, 2020). (in Chinese).
Huang, C. L. et al. The Lancet https://doi.org/10.1016/S0140-6736(20)30183-5 (2020)
Tyrrell DA, Bynoe ML. Cultivation of viruses from a high proportion of patients with colds. Lancet 1966: 1: 76–77.
GISAID Global Initiative on Sharing All Influenza Data. Phylogeny of SARS-like betacoronaviruses including novel coronavirus (nCoV). (Available from: https://nextstrain. org/groups/blab/sars-like-cov).
Zhou P, Yang XL, Wang XG et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020. https://doi.org/10.1038/s41586-020-2012-7
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020 Mar 28;395(10229):1038] [published correction appears in Lancet. 2020 Mar 28;395(10229):1038]. Lancet 2020;395:1054–62. https://doi.org/10.1016/S0140-6736(20)30566-3.
Zhang T, Wu Q, Zhang Z. Probable Pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. CurrBiol 2020;30. https://doi.org/10.1016/j.cub.2020.03.022. 13461351.e2.
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020;109:102433. https://doi.org/10.1016/ j.jaut.2020.102433.
van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1 [published online ahead of print, 2020 Mar 17]. N Engl J Med 2020. https://doi.org/10.1056/NEJMc2004973. NEJMc2004973. ARTICLE IN PRESS 16 CurrProblCardiol, 00 2020
Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible? Lancet GastroenterolHepatol 2020;5:335–7. https://doi.org/10.1016/S2468-1253(20)30048-0.
Zhang H, Kang Z, Gong H, et al. The digestive system is a potential route of 2019- nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv. 2020. https://doi.org/10.1101/2020.01.30.927806.
Chen Y, Peng H, Wang L, et al. Infants born to mothers with a new coronavirus (COVID-19). Front Pediatr 2020;8:104. https://doi.org/10.3389/fped.2020.00104. Published 2020 Mar 16.
Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records [published correction appears in Lancet. 2020 Mar 28;395 (10229):1038] [published correction appears in Lancet. 2020 Mar 28;395(10229):1038]. Lancet 2020;395:809–15. https://doi.org/10.1016/S0140-6736(20)30360-3.
Schwartz DA. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes [published online ahead of print, 2020 Mar 17]. Arch Pathol Lab Med 2020;10. https://doi.org/10.5858/arpa.2020-0901-SA. 5858/ arpa.2020-0901-SA.
Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-coronavirus-2. Int J Infect Dis 2020;94:55–8. https://doi.org/10.1016/j.ijid.2020.03.062.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020. https:// doi.org/10.1056/NEJMc2008597.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020. https://doi.org/10.1001/jamaneurol.2020.1127. Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: properties and future directions. J Neurochem 2008;107:1482–94. https://doi.org/10.1111/ j.1471-4159.2008.05723.x
Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631–7. https://doi.org/10.1002/path.1570.
Chappell MC, Marshall AC, Alzayadneh EM, Shaltout HA, Diz DI. Update on the Angiotensin converting enzyme 2-Angiotensin (1-7)-MAS receptor axis: fetal programing, sex differences, and intracellular pathways. Front Endocrinol (Lausanne) 4: 201–215, 2014. doi:10.3389/fendo. 2013.00201.
Chappell MC. Emerging evidence for a functional ACE2-angiotensin- (1–7)-Mas receptor axis: more than regulation of blood pressure? Hypertension 50: 596–603,2007.doi:10.1161/HYPERTENSIONAHA.106.076216. doi:10.1161/HYPERTENSIONAHA.106.076216.
Sánchez-Aguilar M, Ibarra-Lara L, Del Valle-Mondragón L, RubioRuiz ME, Aguilar-Navarro AG, Zamorano-Carrillo A, Ramírez-Ortega MD, Pastelín-Hernández G, Sánchez-Mendoza A. Rosiglitazone, a ligand to PPAR, improves blood pressure and vascular function through Renin-Angiotensin System regulation. PPAR Res 2019: 1371758, 2019. doi:10.1155/2019/1371758.
Wang W, McKinnie SM, Farhan M, Paul M, McDonald T, McLean B, Llorens-Cortes C, Hazra S, Murray AG, Vederas JC, Oudit GY. Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System. Hypertension 68: 365–377, 2016. doi:10.1161/ HYPERTENSIONAHA.115.06892.
Wang X, Ye Y, Gong H, Wu J, Yuan J, Wang S, Yin P, Ding Z, Kang L, Jiang Q, Zhang W, Li Y, Ge J, Zou Y. The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACEAngII-AT1 and ACE2-Ang(1-7)-Mas axes in pressure overload-induced cardiac remodeling in male mice. J Mol Cell Cardiol 97: 180 –190, 2016. doi:10.1016/j.yjmcc.2016.05.012.
Williams VR, Scholey JW. Angiotensin-converting enzyme 2 and renal disease. CurrOpinNephrolHypertens 27: 35–41, 2018. doi:10.1097/ MNH.0000000000000378.
Wösten-van Asperen RM, Lutter R, Specht PA, Moll GN, van Woensel JB, van der Loos CM, van Goor H, Kamilic J, Florquin S, Bos AP. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. J Pathol 225: 618 –627, 2011. doi:10.1002/ path.2987.
Xu P, Sriramula S, Lazartigues E. ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good. Am J PhysiolRegulIntegr Comp Physiol 300: R804 –R817, 2011. doi:10.1152/ajpregu.00222.2010.
Yuan YM, Luo L, Guo Z, Yang M, Ye RS, Luo C. Activation of renin-angiotensin-aldosterone system (RAAS) in the lung of smokinginduced pulmonary arterial hypertension (PAH) rats. J Renin Angiotensin Aldosterone Syst 16: 249 –253, 2015. doi:10.1177/1470320315576256.
Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., ...&Moch, H. (2020). Endothelial cell infection and endotheliitis in COVID-19. The Lancet, 395(10234), 1417-1418.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–62.
Horton R. Offline: COVID-19—bewilderment and candour. Lancet 2020; 395: 1178.
Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005; 111: 2605–10.
Monteil V KH, Prado P, Hagelkrüys A, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; published online in press. https://www.cell.com/pbassets/products/coronavirus/CELL_ CELL-D-20-00739.pdf (accessed April 17, 2020).
Couturier J, Suliburk JW, Brown JM, et al. Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS (London, England) 2015; 29(6): 667-74.
Nishimura H, Itamura S, Iwasaki T, Kurata T, Tashiro M. Characterization of human influenza A (H5N1) virus infection in mice: neuro-, pneumo- and adipotropic infection. The Journal of General Virology 2000; 81(Pt 10): 2503-10. doi:10.20944/preprints202002.0315.v1
Milner JJ, Rebeles J, Dhungana S, et al. Obesity Increases Mortality and Modulates the Lung Metabolome during Pandemic H1N1 Influenza Virus Infection in Mice. J Immunol 2015; 194(10): 4846-59.
Maier HE, Lopez R, Sanchez N, et al. Obesity Increases the Duration of Influenza A Virus Shedding in Adults. J Infect Dis 2018; 218(9): 1378-82.
Bourgeois C, Gorwood J, Barrail-Tran A, et al. Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence. Frontiers in Microbiology 2019; 10: 2837.
Zhang C, Shi L, Wang F-S. Liver injury in COVID-19: management and challenges. The Lancet Gastroenterology & Hepatology.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. 2020.
Bao, Y., Lin, S. Y., Cheng, Z. H., Xia, J., Sun, Y. P., Zhao, Q., & Liu, G. J. (2020). Clinical Features of COVID‐19 in a Young Man with Massive Cerebral Hemorrhage: Case Report.
Rabi, F. A., Al Zoubi, M. S., Kasasbeh, G. A., Salameh, D. M., & Al-Nasser, A. D. (2020). SARS-CoV-2 and coronavirus disease 2019: What we know so far. Pathogens, 9(3), 231.
Xiong T-Y, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J 2020 [Epub ahead of print].
Wang D, Hu B, Hu C et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA 2020;323:1061-69.
Zhou F, Yu T, Du R et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62.
Arentz M, Yim E, Klaff L et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA 2020 [Epub ahead of print].
Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System. JAMA Cardiol 2020 [Epub ahead of print].
R. Gianotti, P. Zerbi, R. Dodiuk-Gad, Histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy, J. Cosmet. Dermatol. Sci. Appl. (2020) In press.
A.V. Marzano, G. Genovese, G. Fabbrocini, P. Pigatto, G. Monfrecola, B.M. Piraccini, et al., Varicella- like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients, J. Am. Acad. Dermatol. (April 16) (2020), doi:http://dx.doi.org/10.1016/j.jaad.2020.04.044 pii: S0190- 9622(20)30657-5. [Epub ahead of print].
A.W. Swarbrick, S.P. Kumarasinghe, Toxic shock syndrome: a dermatological emergency, Australas. J. Dermatol. 59 (May (2)) (2018) 154–155, doi:http://dx. doi.org/10.1111/ajd.12730 Epub 2017 Sep 27
S. Basetti, J. Hodgson, T.M. Rawson, A. Majeed, Scarlet fever: a guide for general practitioners, London J. Prim. Care (Abingdon) 9 (August (5)) (2017) 77–79, doi:http://dx.doi.org/10.1080/17571472.2017.1365677 eCollection 2017 Sep..
B. Joob, V. Wiwanitkit, COVID-19 can present with a rash and be mistaken for dengue, J. Am. Acad. Dermatol. 82 (May (5)) (2020) e177, doi:http://dx.doi.org/ 10.1016/j.jaad.2020.03.036 Epub 2020 Mar 22
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://doi.org/10.1001/jama.2020.1585. Accessed March 2, 2020.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
Chu KH, Tsang WK, Tang CS, et al. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int. 2005;67: 698–705
Wong SH, Lui RN, Sung JJ. Covid-19 and the digestive system [published online ahead of print, 2020 Mar 25]. J Gastroenterol Hepatol 2020. https://doi.org/10.1111/jgh.15047.
Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929–36. https://doi.org/10.1056/NEJMoa2001191.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497e506. https://doi.org/10.1016/S0140-6736(20) 30183-5.
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420e422. https://doi.org/10.1016/S2213- 2600(20)30076-X.
Cheng YC, Luo R, Wang K, et al. Kidney Impairment Is Associated with In-Hospital Death of COVID-19 Patients; 2020. https://www.medrxiv.org/content/10.1101/2020.02.18. 20023242v1. Accessed February 24, 2020.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507e513. https://doi.org/10.1016/S0140-6736(20)30211-7.
Shewan, L.G., A.J.S. Coats, and M. Henein. Authors’ Responsibilities and Ethical Publishing. in International Cardiovascular Forum Journal. 2018. DOI: 10.17987/icfj. v13i0. 525
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