Preview

Sechenov Medical Journal

Advanced search

Complex mechanism of COVID-19 development

https://doi.org/10.47093/2218-7332.2020.11.2.50-61

Abstract

Coronavirus infection (COVID-19) is an acute viral disease, which affects all vital organs and is caused by an RNA-genomic virus of the genus Betacoronavirus of the family Coronaviridae. This virus (SARS-CoV-2) enters the body through the respiratory tract and interacts primarily with Toll-like receptors of epithelial cells of the bronchi, alveoli, intestines and vascular endotheliocytes, as well as with angiotensin-converting enzyme 2 receptors. Toll-like receptors activate nuclear factor Kappa B in these cells, which initiates the formation of many cytokines (“cytokine storm”). SARS-CoV-2 affects type II pneumocytes by causing a termination of surfactant formation and, accordingly, alveolar shrinking and the formation of acute respiratory distress syndrome and also fibrosis on the interalveolar-capillary membrane and the formation of acute respiratory failure. SARS-CoV-2 and cytokines disrupt the function of vascular endothelial cells, which leads to endothelial dysfunction. In microvessels forms a mass formation of microthrombi, which causes the failure of organs and systems. “Cytokine storm” turns into cytokine sepsis with the formation of multiple organ dysfunction syndrome.

About the Authors

S. B. Bolevich
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Sergey B. Bolevich, MD, PhD, DMSc, Professor, Head of the Human Pathology Department

8/2, Trubetskaya str., Moscow, 119991



S. S. Bolevich
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Stefani S. Bolevich, Assistant Professor, Pathophysiology Department

8/2, Trubetskaya str., Moscow, 119991



References

1. Zheng M., Gao Y., Wang G., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May; 17(5): 533–5. https://doi.org/10.1038/s41423-020-0402-2 PMID: 32203188

2. Li Q., Guan X., Wu P., et al. Early transmission dynamics in Wuhan, China, of Novel Coronavirus-infected pneumonia. N Engl J Med. 2020 Mar 26; 382(13): 1199–207. https://doi.org/10.1056/NEJMoa2001316 PMID: 31995857

3. Wan Y., Shang J., Graham R., et al. Receptor recognition by novel coronavirus from Wuhan: an Analysis based on decade-long structural studies of SARS. J Virol. 2020 Mar 17; 94(7): e00127–20. https://doi.org/10.1128/JVI.00127-20 PMID: 31996437

4. Xiao L., Sakagami H., Miwa N. ACE2: The key molecule for understanding the pathophysiology of severe and critical conditions of COVID-19: Demon or Angel? Viruses. 2020 Apr 28; 12(5): 491. https://doi.org/10.3390/v12050491 PMID: 32354022

5. Chen Y., Guo Y., Pan Y., et al. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020 Feb 17; 525(1): 135–40. https://doi.org/10.1016/j.bbrc.2020.02.071 PMID: 32081428

6. Ziegler C., Allon A.S., Nyquist S.K., et al. SARS-CoV-2 Receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is enriched in specific cell subsets across tissues. Cell. 2020 May 28; 181(5): 1016–35.e19. https://doi.org/10.1016/j.cell.2020.04.035 PMID: 32413319

7. Yuki K., Fujiogi M., Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020 Jun; 8. Zou X., Chen K., Zou J., et al. 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 Apr; 14(2): 185–92. https://doi/org/10.1007/s11684-020-0754-0 PMID: 32170560

8. Zhou P., Yang X.L., Wang X.G., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar; 579(7798): 270–3. https://doi/org/10.1038/s41586-020-2012-7 PMID: 32015507

9. Walls A.C., Park Y.J., Tortorici M.A., et al. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell. 2020 Apr 16; 181(2): 281–92.e6. https://doi.org/10.1016/j.cell.2020.02.058 PMID: 32155444

10. Anand P., Puranik M., Aravamudan М., et al. SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. Elife. 2020 May 26; 9: e58603. https://doi.org/10.7554/eLife.58603 PMID: 32452762

11. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. 2020 Apr 7; 323(13): 1239–42. https://doi.org/10.1001/jama.2020.2648 PMID: 32091533

12. Wu J., Wu X., Zeng W., et al. Chest CT Findings in patients with corona virus disease 2019 and its relationship with clinical features. Invest Radiol. 2020 May; 55(5): 257–61. https://doi.org/10.1097/RLI.0000000000000670 PMID: 32091414

13. Zhang S., Li H., Huang S., et al. High-resolution CT features of 17 cases of corona virus disease 2019 in Sichuan province, China. Eur Respir J. 2020 Apr 30; 55(4): 2000334. https://doi.org/10.1183/13993003.00334-2020 PMID: 32139463

14. Qian Z., Travanty E.A., Oko L., et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. 2013; 48(6): 742–8. https://doi/org/10.1165/rcmb.2012-0339OC PMID: 23418343

15. Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr; 8(4): 420–2. https://doi/org/10.1016/S2213-2600(20)30076-X PMID: 32085846

16. Newton A.H., Cardani A., Braciale T.J. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol. 2016; 38(4): 471–82. https://doi/org/10.1007/s00281-016-0558-0 PMID: 26965109

17. 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 Mar; 63(3): 364–74. https://doi.org/10.1007/s11427-020-1643-8 PMID: 32048163

18. Genschmer K.R., Russell D.W., Lal C., et al. Activated PMN exosomes: pathogenic entities causing matrix destruction and disease in the lung. Cell. 2019 Jan 10; 176(1–2): 113–26.e15. https://doi.org/10.1016/j.cell.2018.12.002 PMID: 30633902

19. Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15; 395(10223): 497–506. https://doi/org/10.1016/S0140-6736(20)30183-5 PMID: 31986264

20. He F., Deng Y., Li W. Coronavirus disease 2019: What we know? J Med Virol. 2020 Mar; 92(7): 719–25. https://doi/org/10.1002/jmv.25766 PMID: 32170865

21. 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 May; 92(5): 491–4. https://doi.org/10.1002/jmv.25709 PMID: 32056249

22. Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr; 8(4): 420–2. https://doi.org/10.1016/S2213-2600(20)30076-X PMID: 32085846

23. Ruan Q., Yang K., Wang W., et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May; 46(5): 846–8. https://doi.org/10.1007/s00134-020-05991-x PMID: 32125452

24. 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 Mar 17; 323(11): 1061–9. https://doi.org/10.1001/jama.2020.1585 PMID: 32031570

25. Kuster G.M., 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 May 14; 41(19): 1801–3. https://doi.org/10.1093/eurheartj/ehaa235 PMID: 32196087

26. Bell T.J., Brand O.J., Morgan D.J., et al. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biol. 2019 Jul; 80: 14–28. https://doi.org/10.1016/j.matbio.2018.06.006 PMID: 2993304

27. Heldin P., Lin C.Y., Kolliopoulos C., et al. Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production. Matrix Biol. 2019 May; 78–9: 100–17. https://doi.org/10.1016/j.matbio.2018.01.017 PMID: 29374576

28. van den Brand J.M.A., Haagmans B.L., van Riel D., et al. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J Comp Pathol. 2014 Jul; 151(1): 83–112. https://doi.org/10.1016/j.jcpa.2014.01.004 PMID: 24581932

29. Lin C.W., Lin K.H., Hsieh T.H., et al. Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunol Med Microbiol. 2006 Apr; 46(3): 375–80. https://doi.org/10.1111/j.1574-695X.2006.00045.x PMID: 16553810

30. Khomich O.A., Kochetkov S.N., Bartosch B., et al. Redox biology of respiratory viral infections. Viruses. 2018 Jul 26; 10(8): 392. https://doi.org/10.3390/v10080392 PMID: 30049972

31. Imai Y., Kuba K., Neely G.G., et al. Identification of Oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008 Apr 18; 133(2): 235–49. https://doi.org/10.1016/j.cell.2008.02.043 PMID: 18423196

32. Gambardella J., Sardu C., Santulli G., et al. Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020 May 11; 9(5): 1417. https://doi.org/10.3390/jcm9051417 PMID: 32403217

33. Escher R., Breakey N., Lammle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020 Jun; 190: 62. https://doi.org/ 10.1016/j.thromres.2020.04.014 PMID: 32305740

34. Schiffrin E.L., Flack J., Ito S., et al. Hypertension and COVID-19. Am J Hypertens. 2020 Apr 6; 33(5): 373–4. https://doi.org/10.1093/ajh/hpaa057 PMID: 32251498

35. Richardson S., Hirsch J.S., Narasimhan M. The Northwell COVID-19 research consortium. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA. 2020 May 26; 323(20): 2052–9. https://doi.org/10.1001/jama.2020.6775 PMID: 32320003

36. Chen T., Wu D., Chen H., et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 2020 Mar 26; 368: m1091. https://doi.org/10.1136/bmj.m1091 PMID: 32217556

37. Myers L.C., Parodi S.M., Escobar G.J., Liu V.X. Characteristics of hospitalized adults with COVID-19 in an integrated health care system in California. JAMA. 2020 Jun 2; 323(21): 2195–8. https://doi/org/10.1001/jama.2020.7202 PMID:32329797

38. Guan W.J., Liang W.H., Zhao Y., et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. Eur Respir J. 2020 May 14; 55(5): 2000547. https://doi.org/10.1183/13993003.00547-2020 PMID: 32217650

39. 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 Mar 28; 395(10229): 1054–62. https://doi.org./10.1016/S0140-6736(20)30566-3 PMID: 32171076

40. Bikdeli B., Madhavan M.V., Jimenez D., et al. Lip GYH. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020 Jun 16; 75(23): 2950–73. https://doi/org/10.1016/j.jacc.2020.04.031 PMID: 32311448

41. Klok F.A., Kruip M., van der Meer N.J.M., et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul; 191: 145–7. https://doi/org 10.1016/j.thromres.2020.04.013 PMID: 32291094

42. Durvasula R., Wellington T., McNamara E., et al. COVID-19 and kidney failure in the acute care setting: our experience from Seattle. Am J Kidney Dis. 2020 Jul; 76(1): 4–6. https://doi.org/10.1053/j.ajkd.2020.04.001 PMID: 32276031

43. Ronco C., Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol. 2020 Jun; 16(6): 308–10. https://doi.org/10.1038/s41581-020-0284-7 PMID: 32273593

44. Rotzinger D.C., Beigelman-Aubry C., von Garnier C., Qanadli S.D. Pulmonary embolism in patients with COVID-19: Time to change the paradigm of computed tomography. Thromb Res. 2020 Jun; 190: 58–9. htpps://doi/org/10.1016/j.thromres.2020.04.011 PMID: 32302782

45. Poissy J., Goutay J., Caplan M., et al. Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence. Circulation. 2020 Jul 14; 142(2): 184–6. https://doi/org/10.1161/CIRCULATIONAHA.120.047430 PMID: 32330083

46. Aggarwal G., Lippi G., Michael Henry B. Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019 (COVID-19): A pooled analysis of published literature. Int J Stroke. 2020 Jun; 15(4): 385–9. https://doi.org/10.1177/1747493020921664 PMID: 32310015

47. Mao L., Jin H., Wang M., et al. Neurologic Manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1; 77(6): 683–90. https://doi/org/10.1001/jamaneurol.2020.1127 PMID: 32275288

48. Riphagen S., Gomez R., Gonzalez-Martinez C., et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020, in press. 2020 May 23; 395(10237): 1607–8. https://doi/org/10.1016/S0140-6736(20)31094-1 PMID: 32386565

49. Lovren F., Pan Y., Quan A., et al. Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Am J Physiol Heart Circ Physiol. 2008 Oct; 295(4): H1377–84. https://doi.org/10.1152/ajpheart.00331.2008 PMID: 18660448

50. Vanarsdall A.L., Pritchard S.R., Wisner T.W. CD147 Promotes entry of pentamer-expressing human cytomegalovirus into epithelial and endothelial cells. mBio. 2018 May 8; 9(3): e00781–18. https://doi.org./10.1128/mBio.00781-18 PMID: 29739904

51. Zhang M.D., Xiao M., Zhang S., et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med. 2020 Apr 23; 382(17): e38. https://doi.org./10.1056/NEJMc2007575 PMID: 32268022

52. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr; 18(4): 844–7. https://doi.org/10.1111/jth.14768 PMID: 32073213

53. 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 Dec; 9(1): 727–32. htps://doi.org/10.1080/22221751.2020.1746199 PMID: 32196410

54. Iba T., Levy J.H., Warkentin T.E., et al. Scientific, Standardization committee on DIC, the S, Standardization Committee on P, Critical Care of the International Society on T and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019 Nov; 17(11): 1989–94. https://doi.org/10.1111/jth.14578 PMID:31410983

55. Abret N., Britton G.J., Gruber C., et al. The Sinai immunology review project. Immunology of COVID-19: Current state of the science. Immunity. 2020 Jun 16; 52(6): 910–41. https://doi.org/10.1016/j.immuni.2020.05.002 PMID: 32505227

56. de Wit E., van Doremalen N., Falzarano D., Munster V.J. SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug; 14(8): 523–34. https://doi.org/10.1038/nrmicro.2016.81 PMID: 27344959

57. Ishiguro T., Matsuo K., Fujii S., Takayanagi N. Acute thrombotic vascular events complicating influenza-associated pneumonia. Respir Med Case Rep. 2019 Jun 14; 28: 100884. https://doi.org/10.1016/j.rmcr.2019.100884 PMID: 31245274

58. Risitano A.M., Mastellos D.C., Huber-Lang M., et al. Complement as a target in COVID-19? Nat Rev Immunol. 2020 Jun; 20(6): 343–4. https://doi.org/10.1038/s41577-020-0320-7 PMID: 32327719


Review

Views: 8909


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2218-7332 (Print)
ISSN 2658-3348 (Online)