Features of immunopathogenesis of a new coronavirus infection

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The main biological characteristics of viruses of the Coronaviridae family are presented. The features of the immunopathogenesis of these infections are analyzed. It was found that the structural proteins of the spine, membrane, envelope and nucleocapsid play an important role in the immunopathogenesis of COVID-19 infection. They are associated with hyperactivation of neutrophils and monocytes-macrophages, secreting large amounts of pro-inflammatory cytokines and chemokines. This contributes to the development of a «cytokine storm» and an unfavorable prognosis of the disease. A particularly high risk of developing pneumonia exists against the background of an increase in the production of: macrophage inflammatory protein-1 alpha, macrophage chemotactic protein, interleukin 8. At the height of infection in some patients, macrophages and dendritic cells infected with SARS-CoV-2 lose their ability to produce type I interferons and pro-inflammatory cytokines. On the part of cellular immunity, a significant decrease in the number of CD4+ and CD8+-lymphocytes was noted. Among IgG sub-isotypes, IgG3 antibodies had the highest reactivity, and IgG1 antibodies were less reactive. Antibodies to spike protein with low specificity or low titer do not neutralize the virus and contribute to the contamination of immunocompetent cells via Fc receptors. Low-affinity antibodies or their low levels can contribute to increased cell sensitivity to SARS-CoV-2 and the development of severe forms of COVID-19 disease.

About the authors

B Y. Gumilevskiy

Military Medical Academy named after S.M. Kirov

Author for correspondence.
Email: alexmav195223@yandex.ru

doctor of medical sciences, professor

Russian Federation, Saint Petersburg

Alexander V. Moskalev

Military Medical Academy named after S.M. Kirov

Email: alexmav195223@yandex.ru

doctor of medical sciences, professor

Russian Federation, Saint Petersburg

Oksana P. Gumilevskaya

Military Medical Academy named after S.M. Kirov

Email: alexmav195223@yandex.ru

doctor of medical sciences, associate professor

Russian Federation, Saint Petersburg

Vasiliy Y. Apcel

Military Medical Academy named after S.M. Kirov, Russian State Pedagogical University named after A.I. Herzen

Email: alexmav195223@yandex.ru

doctor of medical sciences, professor

Russian Federation, Saint Petersburg

Vasiliy N. Tsygan

Military Medical Academy named after S.M. Kirov

Email: alexmav195223@yandex.ru

doctor of medical sciences, professor

Russian Federation, Saint Petersburg

References

  1. Moskalev AV, Sboichakov VB, Rudoy AS. Obshaya immunologiya s osnovami klinicheskoy immunologii. Moscow: GEOTAR-Media; 2015. (In Russ.)
  2. Sboychakov VB, Moskalev AV, et al. Medicinskie laboratornie tehnologii: rukovodstvo po klinicheskoy laboratornoy diagnostike. 3-e ed. Moscow: GEOTAR-Media; 2013. P. 513–568. (In Russ.)
  3. Chen B, Tian EK, He B, et al. Overview of lethal human coronaviruses. Signal Transduct Target Ther. 2020;10:5(1):89. doi: 10.1038/s41392-020-0190-2
  4. Chang HW, de Groot RJ, Egberink HF, Rottier PJ. Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene. J Gen Virol. 2010;91(2):415–420. doi: 10.1099/vir.0.016485-0
  5. Chu H, Zhou J, Wong BH, et al. Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response. Virology. 2014;454–455:197–205. doi: 10.1016/j.virol.2014.02.018
  6. Chan KH, Chan JF, Tse H, et al. Cross-reactive antibodies in convalescent SARS patients’ sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests. J Infect. 2013;67(2):130–140. doi: 10.1016/j.jinf.2013.03.015
  7. Chan JF, Lau SK, To KK, et al. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev. 2015;28(2):465-522. doi: 10.1128/CMR.00102-14
  8. Abaturov AE, Agafonova EA, Krivusha EL, et al. Pathogenesis of Covid-19. Zdorov’e rebenka. 2020;15(2):133–144. (In Russ.)
  9. Chang HW, de Groot RJ, Egberink HF, Rottier PJ. Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene. J Gen Virol. 2010; 91(2):415–420. doi: 10.1099/vir.0.016485-0
  10. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13(9):752–761. doi: 10.1016/S1473-3099(13)70204-4
  11. Assiri A. Middle East respiratory syndrome coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia. Clin Infect Dis. 2016;63:951–53.
  12. Chan KH, Chan JF, Tse H, et al. Cross-reactive antibodies in convalescent SARS patients’ sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests. J Infect. 2013; 67(2):130–140. doi: 10.1016/j.jinf.2013.03.015
  13. Chu H, Chan JF, Wang Y, et al. Comparative Replication and Immune Activation Profiles of SARS-CoV-2 and SARS-CoV in Human Lungs: An Ex Vivo Study With Implications for the Pathogenesis of COVID-19. Clin Infect Dis. 2020;12:71(6):1400–1409. doi: 10.1093/cid/ciaa410
  14. Chu H, Zhou J, Wong BH, et al. Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response. Virology. 2014;454–455:197–205. doi: 10.1016/j.virol.2014.02.018
  15. Decaro N, Mari V, Elia G, et al. Recombinant canine coronaviruses in dogs, Europe. Emerg Infect Dis. 2010;16(1):41–47. doi: 10.3201/eid1601.090726
  16. de Wilde AH, Raj VS, Oudshoorn D, Bestebroer TM, et al. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. J Gen Virol. 2013;94(8):1749–1760. doi: 10.1099/vir.0.052910-0
  17. Chan JF, Lau SK, To KK, et al. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev. 2015;28(2):465–522. doi: 10.1128/CMR.00102-14
  18. de Wilde AH, Raj VS, Oudshoorn D, et al. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. J Gen Virol. 2013;94(8):1749–1760. doi: 10.1099/vir.0.052910-0
  19. 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
  20. 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
  21. Behzadi MA, Leyva-Grado VH. Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections. Front Microbiol. 2019;19(10):1327. doi: 10.3389/fmicb.2019.01327
  22. 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
  23. Belouzard S, Millet JK, Licitra BN, et al. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. 2012;4(6):1011–1033. doi: 10.3390/v4061011
  24. Rose NR. Prediction and Prevention of Autoimmune Disease in the 21st Century: A Review and Preview. Am J Epidemiol. 2016;1:183(5):403–406. doi: 10.1093/aje/kwv292
  25. Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in COVID-19. Nat Rev Immunol. 2020;20(6):339–341. doi: 10.1038/s41577-020-0321-6
  26. 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;17:323(11):1061–1069. doi: 10.1001/jama.2020.1585
  27. Cauchemez S, Fraser C, Van Kerkhove MD, et al. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility. Lancet Infect Dis. 2014;14(1):50–56. doi: 10.1016/S1473-3099(13)70304-9
  28. Hijawi B, Abdallat M, Sayaydeh A, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J. 2013;19(1):12–18. PMID: 23888790
  29. Qin C, Zhou L, Hu Z, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;28:71(15):762–768. doi: 10.1093/cid/ciaa248
  30. Mo Y, Fisher D. A review of treatment modalities for Middle East Respiratory Syndrome. J Antimicrob Chemother. 2016;71(12):3340–3350. doi: 10.1093/jac/dkw338

Copyright (c) 2021 Gumilevskiy B.Y., Moskalev A.V., Gumilevskaya O.P., Apcel V.Y., Tsygan V.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies