DOI: https://doi.org/10.22141/2224-0551.15.2.2020.200598

Pathogenesis of COVID-19

A.E. Abaturov, E.A. Agafonova, E.L. Krivusha, A.A. Nikulina

Abstract


Based on the literature, the article presents modern data on the main pathogenetic features of coronavirus infection associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a pandemic, according to the World Health Organization definition, in 2019. The literature review details the processes of SARS-CoV-2 binding to a human cell receptor that express angiotensin-converting enzyme 2 (ACE2), as well as the internalization, replication of the virus, and the release of new virions from an infected cell, which affect target organs (lungs, digestive tract, heart, central nervous system and kidneys) and induce the development of local and systemic inflammatory respon­ses. Existing methods of drug exposure that prevent human infection with SARS-CoV-2 are described. The main epidemiological moments of infection with SARS-CoV-2 were identified, indica­ting a predominant damage in the elderly and more often males due to the higher level of expression of angiotensin-converting enzyme 2, mostly in alveolocytes, than in females. The mechanisms of the development of the response of the innate and adaptive immune systems of a macroorganism to infection with SARS-CoV-2 are demonstrated. Therapeutic strategies are presented that are related to the effect of SARS-CoV-2 on various stages of vital activity: internalization — the use of soluble S-protein domains, antibodies against S-protein, single-chain variable fragment of antibodies to ACE2 or inhibition of glycosylation of cell receptors, blocking the interaction of SARS-CoV-2 S-protein with ACE2 protein and suppression of internalization of the virus by administration of chloroquine and hydroxychloroquine; replication — inhibition of a viral RNA-dependent RNA polymerase and the use of favipiravir, a non-nucleoside antiviral drug triazavirin, antiretroviral drugs (lopinavir in combination with ritonavir), nelfinavir, ribavirin, halidesivir, umifenovir, inhibitors of chymotrypsin-like protease (cinancerin, flavonoids) and papain-like protease. The above therapeutic me­thods in the near future will be aimed at preventing the development and treatment of both acute respiratory distress syndrome and conditions caused by damage to other targeted organs with COVID-19.


Keywords


coronavirus infection; acute respiratory distress syndrome; pathogenesis; immune response; angiotensin-converting enzyme 2

References


Abaturov AE, Volosovets AP, Yulish EI. Initsiatsiia vospalitel'nogo protsessa pri virusnykh i bakterial'nykh zabolevaniiakh, vozmozhnosti i perspektivy medikamentoznogo upravleniia [The initiation of the inflammatory process in viral and bacterial diseases, the possibilities and prospects of drug management]. Kharkov: LLC S.A.M.; 2011. 392 p. (in Russian).

Alenina N, Bader M. ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models. Neurochem Res. 2019;44(6):1323–1329. doi:10.1007/s11064-018-2679-4.

Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?. Clin Sci (Lond). 2020;134(5):543–545. doi:10.1042/CS20200163.

Bell TJ, Brand OJ, Morgan DJ, et al. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biol. 2019;80:14–28. doi:10.1016/j.matbio.2018.06.006.

Chan JF, Kok KH, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9(1):221–236. doi:10.1080/22221751.2020.1719902.

Chen C, Zhou Y, Wang DW. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020;10.1007/s00059-020-04909-z. doi:10.1007/s00059-020-04909-z.

Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020 Feb 17. doi:10.1016/j.bbrc.2020.02.071.

Collum SD, Chen NY, Hernandez AM, et al. Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis. Br J Pharmacol. 2017;174(19):3284–3301. doi:10.1111/bph.13947.

Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020;55(3):105923. doi:10.1016/j.ijantimicag.2020.105923.

Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2):1. doi:10.23812/CONTI-E.

Cossarizza A, De Biasi S, Guaraldi G, Girardis M, Mussini C; Modena Covid-19 Working Group (MoCo19)#. SARS-CoV-2, the Virus that Causes COVID-19: Cytometry and the New Challenge for Global Health. Cytometry A. 2020;97(4):340–343. doi:10.1002/cyto.a.24002.

Monteleone G, Ardizzone S. Are patients with inflammatory bowel disease at increased risk for Covid-19 infection?. J Crohns Colitis. 2020;jjaa061. doi:10.1093/ecco-jcc/jjaa061.

Duan YJ, Liu Q, Zhao SQ, et al. The Trial of Chloroquine in the Treatment of Corona Virus Disease 2019 (COVID-19) and Its Research Progress in Forensic Toxicology. Fa Yi Xue Za Zhi. 2020;36(2):10.12116/j.issn.1004-5619.2020.02.001. doi:10.12116/j.issn.1004-5619.2020.02.001.

Genschmer KR, Russell DW, Lal C, et al. Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung. Cell. 2019;176(1-2):113–126.e15. doi:10.1016/j.cell.2018.12.002.

Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol. 2015;235(2):185–195. doi:10.1002/path.4454.

Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7(1):11. doi:10.1186/s40779-020-00240-0.

Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020;10.1002/ddr.21656. doi:10.1002/ddr.21656.

Hanff TC, Harhay MO, Brown TS, Cohen JB, Mohareb AM. Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System-a Call for Epidemiologic Investigations. Clin Infect Dis. 2020;ciaa329. doi:10.1093/cid/ciaa329.

He F, Deng Y, Li W. Coronavirus disease 2019: What we know?. J Med Virol. 2020;10.1002/jmv.25766. doi:10.1002/jmv.25766.

Heldin P, Lin CY, Kolliopoulos C, Chen YH, Skandalis SS. Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production. Matrix Biol. 2019;78-79:100–117. doi:10.1016/j.matbio.2018.01.017.

Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Mar 4. doi:10.1016/j.cell.2020.02.052.

Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5.

Thevarajan І, Nguyen THO, Koutsakos М, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020 Mar 16. doi:10.1038/s41591-020-0819-2.

Jin Y, Yang H, Ji W, et al. Virology, Epidemiology, Pathogenesis, and Control of COVID-19. Viruses. 2020;12(4):E372. doi:10.3390/v12040372.

Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34(1):10.23812/20-Editorial-Kritas. doi:10.23812/20-Editorial-Kritas.

Kruse RL. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000Res. 2020;9:72. doi:10.12688/f1000research.22211.2.

Kuba K, Imai Y, Penninger JM. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J. 2013;77(2):301–308. doi:10.1253/circj.cj-12-1544.

Kuster GM, Pfister O, Burkard T, et al. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19?. Eur Heart J. 2020;ehaa235. doi:10.1093/eurheartj/ehaa235.

Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424–432. doi:10.1002/jmv.25685.

Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis. 2020 Mar 5. doi:10.1016/j.jpha.2020.03.001.

Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;10.1002/jmv.25728. doi:10.1002/jmv.25728.

Li Z, Yi Y, Luo X, et al. Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis. J Med Virol. 2020;10.1002/jmv.25727. doi:10.1002/jmv.25727.

Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020;9(1):727–732. doi:10.1080/22221751.2020.1746199.

Liu J, Zheng X, Tong Q, et al. 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. doi:10.1002/jmv.25709.

Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16. doi:10.1038/s41421-020-0156-0.

Liu R, Miller J. China approves use of Roche drug in battle against coronavirus complications. Available from: https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg-idUSKBN20R0LF. Accessed: 2020 Mar 4.

Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364–374. doi:10.1007/s11427-020-1643-8.

Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study. The Lancet. 2020 Mar 2. doi:10.2139/ssrn.3544840.

Matsuyama S, Nao N, Shirato K, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020;117(13):7001–7003. doi:10.1073/pnas.2002589117.

Newton AH, Cardani A, Braciale TJ. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol. 2016;38(4):471–482. doi:10.1007/s00281-016-0558-0.

Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620. doi:10.1038/s41467-020-15562-9.

Paz Ocaranza M, Riquelme JA, García L, et al. Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol. 2020;17(2):116–129. doi:10.1038/s41569-019-0244-8.

Perico L, Benigni A, Remuzzi G. Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade. Nephron. 2020;1–9. doi:10.1159/000507305.

Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38(1):1–9. doi:10.12932/AP-200220-0772.

Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;S0006-291X(20)30523-4. doi:10.1016/j.bbrc.2020.03.044.

Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;ciaa248. doi:10.1093/cid/ciaa248.

Rabi FA, Al Zoubi MS, Kasasbeh GA, Salameh DM, Al-Nasser AD. SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far. Pathogens. 2020;9(3):E231. doi:10.3390/pathogens9030231.

Remuzzi A, Remuzzi G. COVID-19 and Italy: what next?. Lancet. 2020 Mar 13. doi:10.1016/S0140-6736(20)30627-9.

Rismanbaf A, Zarei S. Liver and Kidney Injuries in COVID-19 and Their Effects on Drug Therapy; a Letter to Editor. Arch Acad Emerg Med. 2020;8(1):e17.

Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;1–3. doi:10.1007/s00134-020-05991-x.

Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020;10.1038/s41418-020-0530-3. doi:10.1038/s41418-020-0530-3.

Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020;87(4):281–286. doi:10.1007/s12098-020-03263-6.

Sun D, Li H, Lu XX, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatr. 2020;10.1007/s12519-020-00354-4. doi:10.1007/s12519-020-00354-4.

Sun P, Lu X, Xu C, Sun W, Pan B. Understanding of COVID-19 based on current evidence. J Med Virol. 2020;10.1002/jmv.25722. doi:10.1002/jmv.25722.

Sun T, Guan J. Novel coronavirus and central nervous system. Eur J Neurol. 2020;10.1111/ene.14227. doi:10.1111/ene.14227.

Tian X, Li C, Huang A, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020;9(1):382–385. doi:10.1080/22221751.2020.1729069.

Totura AL, Baric RS. SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr Opin Virol. 2012;2(3):264–275. doi:10.1016/j.coviro.2012.04.004.

Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020;177:104762. doi:10.1016/j.antiviral.2020.104762.

Tyrrell DA, Bynoe ML. Cultivation of viruses from a high proportion of patients with colds. Lancet. 1966;1(7428):76–77. doi:10.1016/s0140-6736(66)92364-6.

Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health. 2020;25(3):278–280. doi:10.1111/tmi.13383.

Anti-2019-nCoV Volunteers; Li Z, Wu M, Guo J, et al. Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv. 2020 Mar 27. doi:10.1101/2020.02.08.20021212.

Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020 Mar 6. doi:10.1016/j.cell.2020.02.058.

Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol. 2020;94(7):e00127-20. doi:10.1128/JVI.00127-20.

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;e201585. doi:10.1001/jama.2020.1585.

Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271. doi:10.1038/s41422-020-0282-0.

Wevers BA, van der Hoek L. Renin-angiotensin system in human coronavirus pathogenesis. Future Virol. 2010;5(2):145–161. doi:10.2217/fvl.10.4.

Wong HH, Fung TS, Fang S, Huang M, Le MT, Liu DX. Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3. Virology. 2018;515:165–175. doi:10.1016/j.virol.2017.12.028.

Wong SH, Lui RN, Sung JJ. Covid-19 and the Digestive System. J Gastroenterol Hepatol. 2020;10.1111/jgh.15047. doi:10.1111/jgh.15047.

Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. doi:10.1126/science.abb2507.

Wysocki J, Schulze A, Batlle D. Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System. Biomolecules. 2019;9(12):886. doi:10.3390/biom9120886.

Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8. doi:10.1038/s41368-020-0074-x.

Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi:10.1016/S2213-2600(20)30076-X.

Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367(6485):1444–1448. doi:10.1126/science.abb2762.

Yi Y, Lagniton PNP, Ye S, Li E, Xu RH. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci. 2020;16(10):1753–1766. doi:10.7150/ijbs.45134.

Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586–590. doi:10.1007/s00134-020-05985-9.

Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020;92(5):479–490. doi:10.1002/jmv.25707.

Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;10.1038/s41569-020-0360-5. doi:10.1038/s41569-020-0360-5.

Zhou N, Pan T, Zhang J, et al. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). J Biol Chem. 2016;291(17):9218–9232. doi:10.1074/jbc.M116.716100.

Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. doi:10.1056/NEJMoa2001017.

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;10.1007/s11684-020-0754-0. doi:10.1007/s11684-020-0754-0.






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