Особенности иммунного ответа при COVID-19

АКТУАЛЬНОСТЬ Данный обзор посвящен анализу особенностей иммунного ответа при COVID-19. В обзоре указаны клинические проявления COVID-19, рассмотрены современные данные об иммунопатогенезе заболевания и его осложнений.

ЦЕЛЬ Прояснить некоторые патогенетические механизмы иммунного ответа при COVID-19, что может помочь в создании алгоритма обследования пациентов для раннего прогноза и профилактики тяжелого течения и осложнений заболевания.

МАТЕРИАЛ И МЕТОДЫ Для достижения поставленной цели были проанализированы результаты отечественных и зарубежных научных исследований, посвященных патогенезу, диагностике и лечению COVID-19. Поиск литературы проводился в электронных поисковых системах Scopus и PubMed. Для анализа были отобраны научные статьи, опубликованные в период с 2019 по 2021 год; 88% проанализированных работ не старше 5 лет.

ЗАКЛЮЧЕНИЕ Наибольшее значение для развития тяжелой формы COVID-19 имеет поздняя продукция IFN типа I, повышение уровня в крови провоспалительных моноцитов, снижение экспрессии HLA-DR на моноцитах, нарушение презентации вируса и формирования специфических лимфоцитов, гибель Т-лимфоцитов и глубокая иммуносупрессия.

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. PMID: 31978945 https://doi.org/10.1056/ NEJMoa2001017

2. WHO Director-General’s Opening Remarks at the Media Briefing on COVID-19 – 11 March 2020. Available at: https://www.who.int/directorgeneral/speeches/detail/who-director-general-s-opening-remarks-atthe-media-briefing-on-covid-19---11-march-2020 [Accessed January 21, 2022].

3. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020;382(16):1564–1567. PMID: 32182409 https://doi.org/10.1056/NEJMc2004973

4. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. 2020;94(7):e00127–20. PMID: 31996437 https:// doi.org/10.1128/JVI.00127-20

5. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. 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.e8. PMID: 32142651 https://doi.org/10.1016/ j.cell.2020.02.052

6. Fung SY, Yuen KS, Ye ZW, Chan CP, Jin DY. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect. 2020;9(1):558–570. PMID: 32172672 https://doi.org/10.1080/22221751 .2020.1736644

7. Wu Z, McGoogan JM. 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;323(13):1239–1242. PMID: 32091533 https:// doi.org/10.1001/jama.2020.2648

8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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(10229):1054– 1062. PMID: 32171076 https://doi.org/10.1016/S0140-6736(20)30566-3

9. Cavalcante-Silva LHA, Carvalho DCM, Lima ÉA, Galvão JGFM, da Silva JSF, Sales-Neto JM, et al. Neutrophils and COVID-19: The road so far. Int Immunopharmacol. 2021;90:107233. PMID: 33290963 https://doi. org/10.1016/j.intimp.2020.107233

10. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19): временные методические рекомендации. Версия 13.1 (17.11.2021). Москва; 2021.

11. van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, et al. Presence of Genetic Variants Among Young Men with Severe COVID-19. JAMA. 2020;324(7):663–673. PMID: 32706371 https://doi.org/10.1001/jama.2020.13719

12. Zhu J, Mohan C. Toll-Like receptor signaling pathways—therapeutic opportunities. Mediators Inflamm. 2010;2010:781235. PMID: 20981241 https://doi.org/10.1155/2010/781235

13. Knoll R, Schultze JL, Schulte-Schrepping J. Monocytes and Macrophages in COVID-19. Front Immunol. 2021;12:720109. PMID: 34367190https:// doi.org/10.3389/fimmu.2021.720109

14. Долгов В.В. (ред.) Клиническая лабораторная диагностика: в 2-х т. Т. 1. Москва: Лабдиаг; 2017.

15. Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health. 2020;13(11):1619– 1629. PMID: 32718895 https://doi.org/10.1016/j.jiph.2020.07.001

16. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7(6):998–1002. PMID: 34676125 https://doi.org/10.1093/nsr/nwaa041

17. Boyette LB, Macedo C, Hadi K, Elinoff BD, Walters JT, Ramaswami B, et al. Phenotype, function, and differentiation potential of human monocyte subsets. PLoS One. 2017;12(4):e0176460. PMID: 28445506 https://doi.org/0.1371/journal.pone.0176460

18. Zhuang Y, Peng H, Chen Y, Zhou S, Chen Y. Dynamic monitoring of monocyte HLA-DR expression for the diagnosis, prognosis, and prediction of sepsis. Front Biosci (Landmark Ed). 2017;22:1344–1354. PMID: 28199206 https://doi.org/10.2741/4547

19. Napoli C, Benincasa G, Criscuolo C, Faenza M, Liberato C, Rusciano M. Immune reactivity during COVID-19: Implications for treatment. Immunol Lett. 2021;231:28–34. PMID: 33421440 https://doi.org/10.1016/ j.imlet.2021.01.001

20. Monneret G, Gossez M, Aghaeepour N, Gaudilliere B, Venet F. How Clinical Flow Cytometry Rebooted Sepsis Immunology. Cytometry A. 2019;95(4):431–441. PMID: 30887636 https://doi.org/10.1002/cyto. a.23749

21. Ohno Y, Kitamura H, Takahashi N, Ohtake J, Kaneumi S, Sumida K, et al. IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4(+) T cells. Cancer Immunol Immunother. 2016;65(2):193–204. PMID: 26759006 https://doi.org/10.1007/s00262-015-1791-4

22. Fu B, Xu X, Wei H.Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med. 2020;18(1):164. PMID: 32290839 https://doi.org/10.1186/s12967-020-02339-3

23. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992–1000.e3. PMID: 32320677 https://doi.org/10.1016/ j.chom.2020.04.009

24. Meidaninikjeh S, Sabouni N, Marzouni HZ, Bengar S, Khalili A, Jafari R. Monocytes and macrophages in COVID-19: Friends and foes. Life Sci. 2021;269:119010. PMID: 33454368 https://doi.org/10.1016/ j.lfs.2020.119010

25. Bassler K, Schulte-Schrepping J, Warnat-Herresthal S, Aschenbrenner AC, Schultze JL. The Myeloid Cell Compartment-Cell by Cell. Annu Rev Immunol. 2019;37:269–293. PMID: 30649988 https://doi.org/10.1146/ annurev-immunol-042718-041728

26. Kapellos TS, Bonaguro L, Gemünd I, Reusch N, Saglam A, Hinkley ER, et al. Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases. Front Immunol. 2019;10:2035. PMID: 31543877 https://doi.org/10.3389/fimmu.2019.02035

27. Merino A, Buendia P, Martin-Malo A, Aljama P, Ramirez R. Carracedo J. Senescent CD14+CD16+ Monocytes Exhibit Proinflammatory and Proatherosclerotic Activity. J Immunol. 2011;186(3):1809–1815. PMID: 21191073 https://doi.org/10.4049/jimmunol.1001866

28. Васильева Е.Ф., Брусов О.С. Роль моноцитов в клеточно-молекулярных механизмах развития системного иммунного воспаления. Часть 1. Психиатрия. 2020;18(3):76–85. https://doi.org/10.30629/2618- 6667-2020-18-3-76-85

29. Strauss-Ayali D, Conrad SM, Mosser DM. Monocyte subpopulations and their differentiation patterns during infection. J Leukoc Biol. 2007;82(2):244–52. PMID: 17475785 https://doi.org/10.1189/ jlb.0307191

30. Misharin AV, Morales-Nebreda L, Reyfman PA, Cuda CM, Walter JM, McQuattie-Pimentel AC, et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J Exp Med. 2017;214(8):2387–2404. PMID: 28694385 https://doi.org/10.1084/ jem.20162152

31. Ярилин А.А. Иммунология. Москва: ГЭОТАР-Медиа; 2010.

32. Калашникова А.А., Ворошилова Т.М., Чиненова Л.В., Давыдова Н.И., Калинина Н.М. Субпопуляции моноцитов у здоровых лиц и у пациентов с сепсисом. Медицинская иммунология. 2018;20(6):815– 824.

33. Zhu H, Ding Y, Zhang Y, Ding X, Zhao J, Ouyang W, et al. CTRP3 induces an intermediate switch of CD14++CD16+ monocyte subset with antiinflammatory phenotype. Exp Ther Med. 2020;199(3):2243–2251. PMID: 32104290 https://doi.org/10.3892/etm.2020.8467

34. Zhu M, Lei L, Zhu Z, Li Q, Guo D, Xu J, et al. Excess TNF-D in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells. Acta Biochim Biophys Sin (Shanghai). 2015;47(11):899– 907. PMID: 26373842 https://doi.org/10.1093/abbs/gmv092

35. Kim JS, Lee JY, Yang JW, Lee KH, Effenberger M, Szpirt W, et al. Immunopathogenesis and treatment of cytokine storm in COVID19. Theranostics. 2021;11(1):316–329. PMID: 33391477 https://doi. org/10.7150/thno.49713

36. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–481. PMID: 32105632 https://doi.org/10.1016/S2213- 2600(20)30079-5

37. Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020;11:1446. PMID: 32612617 https://doi.org/10.3389/fimmu.2020.01446

38. McGonagle D, Sharif K, O’Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020;19(6):102537. PMID: 32251717 https://doi.org/10.1016/ j.autrev.2020.102537

39. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect. 2020;80(6):607–613. PMID: 32283152 https://doi.org/10.1016/j.jinf.2020.03.037

40. Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Moller R, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020;181(5):1036–1045.e9. PMID: 32416070 https:// doi.org/10.1016/j.cell.2020.04.026

41. Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. Impaired type I interferone activity and inflammatory responses in severe Covid-19 patients. Science. 2020;369(6504):718–724. PMID: 32661059 https://doi.org/10.1126/science.abc6027

42. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033– 1034. PMID: 32192578 https://doi.org/10.1016/S0140-6736(20)30628-0

43. Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020;53:66–70. PMID: 32418715 https://doi.org/10.1016/ j.cytogfr.2020.05.002

44. Kim JS, Lee JY, Yang JW, Lee KH, Effenberger M, Szpirt W, et al. Immunopathogenesis and treatment of cytokine storm in COVID19. Theranostics. 2021;11(1):316–329. PMID: 33391477 https://doi. org/10.7150/thno.49713

45. Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol. 2020;92(11):2283–2285. PMID: 32343429 https://doi.org/10.1002/jmv.25948

46. Liu F, Li L, Xu M, Wu J, Luo D, Zhu Y, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370. PMID: 32344321 https://doi. org/10.1016/j.jcv.2020.104370

47. Yang P, Ding Y, Xu Z, Pu R, Li P, Yan J, et al. Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China. MedRxiv. 2020. Available at: https://www.medrxiv.org/ content/10.1101/2020.02.28.20028068v1 [Accessed January 24, 2022]. https://doi.org/10.1101/2020.02.28.20028068

48. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123–1130. PMID: 32475230 https://doi.org/10.1080/22221751.2020.1770129

49. Lu L, Zhang H, Dauphars DJ, He YW A Potential Role of Interleukin 10 in COVID-19 Pathogenesis. Trends Immunol. 2021;42(1):3–5. PMID: 33214057 https://doi.org/10.1016/j.it.2020.10.012

50. Satış H, Özger HS, Aysert Yıldız P, Hızel K, Gulbahar Ö, Erbaş G, et al. Prognostic value of interleukin-18 and its association with otherinflammatory markers and disease severity in COVID-19. Cytokine. 2021;137:155302. PMID: 33002740 https://doi.org/10.1016/ j.cyto.2020.155302

51. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, MelguizoRodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:62–75. PMID: 32513566 https://doi.org/10.1016/j.cytogfr.2020.06.001

52. Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020;11:827. PMID: 32425950 https:// doi.org/10.3389/fimmu.2020.00827

53. Pence BD. PenceSevere COVID-19 and aging: are monocytes the key? Geroscience. 2020;42(4):1051–1061. PMID: 32556942 https://doi. org/10.1007/s11357-020-00213-0

54. Zhang F, Gan R, Zhen Z, Hu X, Li X, Zhou F, et al. Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals. Signal Transduct Target Ther. 2020;5(1):156. PMID: 32796814 https:// doi.org/10.1038/s41392-020-00263-y

55. Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ, McKechnie JL, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020;26(7):1070–1076. PMID: 32514174 https://doi.org/10.1038/s41591-020-0944-y

56. Grant RA, Morales-Nebreda L, Markov NS, Swaminathan S, Querrey M, Guzman ER, et al. Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Nature. 2021;590(7847):635–641. PMID: 33429418 https://doi.org/10.1038/s41586-020-03148-w

57. Rezaei M, Mahmoudi S, Mortaz E, Marjani M. Immune cell profiling and antibody responses in patients with COVID-19. BMC Infect Dis. 2021;21(1):646. PMID: 34225645 https://doi.org/10.1186/s12879-021- 06278-2

58. López-Collazo E, Avendaño-Ortiz J, Martín-Quirós A, Aguirre LA. Immune Response and COVID-19: A mirror image of Sepsis. Int J Biol Sci. 2020;16(14):2479–2489. PMID: 32792851 https://doi.org/10.7150/ ijbs.48400

59. Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 2021;184(1):149–168.e17. PMID: 33278357 https://doi.org/10.1016/j.cell.2020.11.025

60. Anka AU, Tahir MI, Abubakar SD, Alsabbagh M, Zian Z, Hamedifar H, et al. Coronavirus disease 2019 (COVID-19): An overview of the immunopathology, serological diagnosis and management. Scand J Immunol. 2021;93(4):e12998. PMID: 33190302 https://doi.org/10.1111/ sji.12998

61. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. Targets of T cell responses to SARS-CoV2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020;181(7):1489–1501.e15. PMID: 32473127 https://doi.org/10.1016/ j.cell.2020.05.015