Иммунологические подходы к лечению новой коронавирусной инфекции (обзор)

Пандемия новой коронавирусной инфекции (COVID-19), вызванной вирусом SARS-CoV-2, охватила абсолютное большинство стран мира. Ежедневно появляется большой объем информации, которая требует осмысления и систематизации. Одно из важ­ных направлений исследований — изучение иммунологических аспектов взаимодействия вируса и макроорганизма, понимание которых необходимо для разработки средств эффективного лечения и профилактики COVID-19.

В обзоре проанализированы знания о путях вирусной инвазии и эвазии, механизмах развития цитокинового шторма, эндотелиального повреждения и гиперкоагуляции, связанных с инфекцией SARS-CoV-2. Приняты во внимание фундаментальные и клинические данные, полученные в ходе предыдущих эпидемий SARS и MERS. Обсуждаются возможные терапевтические подходы, основанные на исследовании механизмов формирования иммунного ответа и регуляции функции клеток системы крови, а также изучении снижения избыточного иммунного ответа. Рассмотрены подходы к интерферонотерапии, противовоспалительной терапии, антицитокиновой терапии, применению нейтрализующих антител, плазмы реконвалесцентов, мезенхимальных стволовых клеток, а также к вакцинопрофилактике.

1. WHO coronavirus disease (COVID-19) dashboard. URL: https://covid19.who.int.
2. 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 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323(13): 1239–1242, https://doi.org/10.1001/jama.2020.2648.
3. de Wit E., van Doremalen N., Falzarano D., Munster V.J. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016; 14(8): 523–534, https://doi.org/10.1038/nrmicro.2016.81.
4. Du L., He Y., Zhou Y., Liu S., Zheng B.J., Jiang S. The spike protein of SARS-CoV — a target for vaccine and therapeutic development. Nat Rev Microbiol 2009; 7(3): 226–236, https://doi.org/10.1038/nrmicro2090.
5. Du L., Yang Y., Zhou Y., Lu L., Li F., Jiang S. MERS-CoV spike protein: a key target for antivirals. Expert Opin Ther Targets 2017; 21(2): 131–143, https://doi.org/10.1080/14728222.2017.1271415.
6. Fauci A.S., Lane H.C., Redfield R.R. COVID-19 — navigating the uncharted. N Engl J Med 2020; 382(13): 1268–1269, https://doi.org/10.1056/nejme2002387.
7. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., Huan Y., Yang P., Zhang Y., Deng W., Bao L., Zhang B., Liu G., Wang Z., Chappell M., Liu Y., Zheng D., Leibbrandt A., Wada T., Slutsky A.S., Liu D., Qin C., Jiang C., Penninger J.M. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005; 11(8): 875–879, https://doi.org/10.1038/nm1267.
8. Guo Y., Korteweg C., McNutt M.A., Gu J. Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Res 2008; 133(1): 4–12, https://doi.org/10.1016/j.virusres.2007.01.022.
9. Lukassen S., Chua L.R., Trefzer T., Kahn N.C., Schneider M.A., Muley T., Winter H., Meister M., Veith C., Boots A.W., Hennig B.P., Kreuter M., Conrad C., Eils R. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J 2020; 39(10): e105114, https://doi.org/10.15252/embj.20105114.
10. Guzzi P.H., Mercatelli D., Ceraolo C., Giorgi F.M. Master regulator analysis of the SARS-CoV-2/human interactome. J  Clin Med 2020; 9(4): 982, https://doi.org/10.3390/jcm9040982.
11. Sokolowska M., Lukasik Z.M., Agache I., Akdis C.A., Akdis D., Akdis M., Barcik W., Brough H.A., Eiwegger T., Eljaszewicz A., Eyerich S., Feleszko W., Gomez-Casado C., Hoffmann-Sommergruber K., Janda J., Jiménez-Saiz R., Jutel M., Knol E.F., Kortekaas Krohn I., Kothari A., Makowska J., Moniuszko M., Morita H., O’Mahony L., Nadeau K., Ozdemir C., Pali-Schöll I., Palomares O., Papaleo F., Prunicki M., Schmidt-Weber C.B., Sediva A., Schwarze J., Shamji M.H., Tramper-Stranders G.A., van de Veen W., Untersmayr E. Immunology of COVID-19: mechanisms, clinical outcome, diagnostics, and perspectives — a report of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy 2020; 75(10): 2445–2476, https://doi.org/10.1111/all.14462.
12. Channappanavar R., Fehr A.R., Vijay R., Mack M., Zhao J., Meyerholz D.K., Perlman S. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe 2016; 19(2): 181–193, https://doi.org/10.1016/j.chom.2016.01.007.
13. Channappanavar R., Fehr A.R., Zheng J., Wohlford-Lenane C., Abrahante J.E., Mack M., Sompallae R., McCray P.B. Jr., Meyerholz D.K., Perlman S. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Invest 2019; 129(9): 3625–3639, https://doi.org/10.1172/jci126363.
14. Blanco-Melo D., Nilsson-Payant B.E., Liu W.C., Uhl S., Hoagland D., Møller R., Jordan T.X., Oishi K., Panis M., Sachs D., Wang T.T., Schwartz R.E., Lim J.K., Albrecht R.A., tenOever B.R. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 2020; 181(5): 1036–1045, https://doi.org/10.1016/j.cell.2020.04.026.
15. Lokugamage K.G., Hage A., de Vries M., Valero-Jimenez A.M., Schindewolf C., Dittmann M., Rajsbaum R., Menachery V.D. SARS-CoV-2 is sensitive to type I interferon pretreatment. bioRxiv 2020; 2020.03.07.982264, https://doi.org/10.1101/2020.03.07.982264.
16. Mantlo E.K., Bukreyeva N., Maruyama J., Paessler S., Huang C. Antiviral activities of type I interferons to SARS-CoV-2 infection. Antiviral Res 2020; 179: 104811, https://doi.org/10.1016/j.antiviral.2020.104811.
17. Stanifer M.L., Kee C., Cortese M., Zumaran C.M., Triana S., Mukenhirn M., Kraeusslich H.G., Alexandrov T., Bartenschlager R., Boulant S. Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells. Сell Reports 2020; 32(1): 197863, https://doi.org/10.1016/j.celrep.2020.107863.
18. Cameron M.J., Kelvin A.A., Leon A.J., Cameron C.M., Ran L., Xu L., Chu Y.K., Danesh A., Fang Y., Li Q., Anderson A., Couch R.C., Paquette S.G., Fomukong N.G., Kistner O., Lauchart M., Rowe T., Harrod K.S., Jonsson C.B., Kelvin D.J. Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model. PLoS One 2012; 7(9): e45842, https://doi.org/10.1371/journal.pone.0045842.
19. Minakshi R., Padhan K., Rani M., Khan N., Ahmad F., Jameel S. The SARS coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS One 2009; 4(12): e8342, https://doi.org/10.1371/journal.pone.0008342.
20. Wathelet M.G., Orr M., Frieman M.B., Baric R.S. Severe acute respiratory syndrome coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain. J Virol 2007; 81(21): 11620–11633, https://doi.org/10.1128/jvi.00702-07.
21. Spiegel M., Pichlmair A., Martínez-Sobrido L., Cros J., García-Sastre A., Haller O., Weber F. Inhibition of Beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J Virol 2005; 79(4): 2079–2086, https://doi.org/10.1128/jvi.79.4.2079-2086.2005.
22. Lu X., Pan J., Tao J., Guo D. SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism. Virus Genes 2011; 42(1): 37–45, https://doi.org/10.1007/s11262-010-0544-x.
23. Hadjadj J., Yatim N., Barnabei L., Corneau A., Boussier J., Péré H., Charbit B., Bondet V., Chenevier-Gobeaux C., Breillat P., Carlier N., Gauzit R., Morbieu C., Pène F., Marin N., Roche N., Szwebel T.A., Merkling S.H., Treluyer J.M., Veyer D., Mouthon L., Blanc C., Tharaux P.L., Rozenberg F., Fischer A., Duffy D., Rieux-Laucat F., Kernéis S., Terrier B. Impaired type I interferon activity and exacerbated inflammatory responses in severe COVID-19 patients. Science 2020; 369(6504): 718–724, https://doi.org/10.1126/science.abc6027.
24. Li J., Guo M., Tian X., Liu C., Wang X., Yang X., Wu P., Xiao Z., Qu Y., Yin Y., Wang C., Zhang Y., Zhu Z., Liu Z., Peng C., Zhu T., Liang Q. Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis. Med (NY) 2021; 2(1): 99–112.e7, https://doi.org/10.1016/j.medj.2020.07.002.
25. Travaglini K.J., Nabhan A.N., Penland L., Sinha R., Gillich A., Sit R.V., Chang S., Conley S.D., Mori Y., Seita J., Berry G.J., Shrager J.B., Metzger R.J., Kuo C.S., Neff N., Weissman I.L., Quake S.R., Krasnow M.A. A molecular cell atlas of the human lung from single cell RNA sequencing. Nature 2020; 587(78350): 619–625, https://doi.org/10.1038/s41586-020-2922-4.
26. Liu J., Li S., Liu J., Liang B., Wang X., Wang H., Li W., Tong Q., Yi J., Zhao L., Xiong L., Guo C., Tian J., Luo J., Yao J., Pang R., Shen H., Peng C., Liu T., Zhang Q., Wu J., Xu L., Lu S., Wang B., Weng Z., Han C., Zhu H., Zhou R., Zhou H., Chen X., Ye P., Zhu B., Wang L., Zhou W., He S., He Y., Jie S., Wei P., Zhang J., Lu Y., Wang W., Zhang L., Li L., Zhou F., Wang J., Dittmer U., Lu M., Hu Y., Yang D., Zheng X. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763, https://doi.org/10.1016/j.ebiom.2020.102763.
27. Wang F., Nie J., Wang H., Zhao Q., Xiong Y., Deng L., Song S., Ma Z., Mo P., Zhang Y. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis 2020; 221(11): 1762–1769, https://doi.org/10.1093/infdis/jiaa150.
28. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., Tian D.S. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020; 71(15): 762–768, https://doi.org/10.1093/cid/ciaa248.
29. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., Xu Y., Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 2020; 17(5): 533–535, https://doi.org/10.1038/s41423-020-0402-2.
30. National Research Project for SARS; Beijing Group. The involvement of natural killer cells in the pathogenesis of severe acute respiratory syndrome. Am J Clin Pathol 2004; 121(4): 507–511, https://doi.org/10.1309/wpk7-y2xk-nf4c-bf3r.
31. Wilk A.J., Rustagi A., Zhao N.Q., Roque J., Martínez-Colón G.J., McKechnie J.L., Ivison G.T., Ranganath T., Vergara R., Hollis T., Simpson L.J., Grant P., Subramanian A., Rogers A.J., Blish C.A. A single-cell atlas of the peripheral immune response to severe COVID-19. Nature Medicine 2020; 26(7): 1070–1076, https://doi.org/10.1038/s41591-020-0944-y.
32. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497–506, https://doi.org/10.1016/s0140-6736(20)30183-5.
33. Wang W., Liu X., Wu S., Lie P., Huang L., Li Y., Cheng L., Chen S., Nong L., Lin Y., He J. The definition and risks of cytokine release syndrome-like in 11 COVID-19-infected pneumonia critically ill patients: disease characteristics and retrospective analysis. medRxiv 2020; 222(9): 1444–1451, https://doi.org/10.1101/2020.02.26.20026989.
34. Cifaldi L., Prencipe G., Caiello I., Bracaglia C., Locatell F., De Benedetti F., Strippoli R. Inhibition of natural killer cell cytotoxicity by interleukin-6: implications for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatol 2015; 67(11): 3037–3046, https://doi.org/10.1002/art.39295.
35. Lee J., Lee S.H., Shin N., Jeong M., Kim M.S., Kim M.J., Yoon S.R., Chung J.W., Kim T.D., Choi I. Tumor necrosis factor-α enhances IL-15-induced natural killer cell differentiation. Biochem Biophys Res Commun 2009; 386(4): 718–723, https://doi.org/10.1016/j.bbrc.2009.06.120.
36. Guo C., Li B., Ma H., Wang X., Cai P., Yu Q., Zhu L., Jin L., Jiang C., Fang J., Liu Q., Zong D., Zhang W., Lu Y., Li K., Gao X., Fu B., Liu L., Ma X., Weng J., Wei H., Jin T., Lin J., Qu K. Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm. Nat Commun 2020; 11(1): 3924, https://doi.org/10.1038/s41467-020-17834-w.
37. Liao M., Liu Y., Yuan J., Wen Y., Xu G., Zhao J., Cheng L., Li J., Wang X., Wang F., Liu L., Amit I., Zhang S., Zhang Z. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nature Medicine 2020, 26: 842–844, https://doi.org/10.1038/s41591-020-0901-9.
38. Chen I.Y., Moriyama M., Chang M.F., Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol 2019; 10: 50, https://doi.org/10.3389/fmicb.2019.00050.
39. Zhou Y., Fu B., Zheng X., Wang D., Zhao C., Qi Y., Sun R., Tian Z., Xu X., Wei H. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. National Sci Rev 2020; 7(6): 998–1002, https://doi.org/10.1093/nsr/nwaa041.
40. 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, https://doi.org/10.1016/j.autrev.2020.102537.
41. Nairz M., Theurl I., Swirski F.K., Weiss G. “Pumping iron” — how macrophages handle iron at the systemic, microenvironmental, and cellular levels. Pflugers Arch 2017; 469(3–4): 397–418, https://doi.org/10.1007/s00424-017-1944-8.
42. Velavan T.P., Meyer C.G. Mild versus severe COVID-19: laboratory markers. Int J Infect Dis 2020; 95: 304–307, https://doi.org/10.1016/j.ijid.2020.04.061.
43. Giamarellos-Bourboulis E.J., Netea M.G., Rovina N., Akinosoglou K., Antoniadou A., Antonakos N., Damoraki G., Gkavogianni T., Adami M.E., Katsaounou P., Ntaganou M., Kyriakopoulou M., Dimopoulos G., Koutsodimitropoulos I., Velissaris D., Koufargyris P., Karageorgos A., Katrini K., Lekakis V., Lupse M., Kotsaki A., Renieris G., Theodoulou D., Panou V., Koukaki E., Koulouris N., Gogos C., Koutsoukou A. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020; 27(6): 992–1000, https://doi.org/10.1016/j.chom.2020.04.009.
44. Zhou Y., Fu B., Zheng X., Wang D., Zhao C., Qi Y., Sun R., Tian Z., Xu X., Wei H. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. Natl Sci Rev 2020; 7(6): 998–1002, https://doi.org/10.1101/2020.02.12.945576.
45. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J.; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395(10229): 1033–1034, https://doi.org/10.1016/s0140-6736(20)30628-0.
46. Prokunina-Olsson L., Alphonse N., Dickenson R.E., Durbin J.E., Glenn J.S., Hartmann R., Kotenko S.V., Lazear H.M., O’Brien T.R., Odendall C., Onabajo O.O., Piontkivska H., Santer D.M., Reich N.C., Wack A., Zanoni I. COVID-19 and emerging viral infections: the case for interferon lambda. J Exp Med 2020; 217(5): e20200653, https://doi.org/10.1084/jem.20200653.
47. Tanaka T., Narazaki M., Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy 2016; 8(8): 959–970, https://doi.org/10.2217/imt-2016-0020.
48. Barnes B.J., Adrover J.M., Baxter-Stoltzfus A., Borczuk A., Cools-Lartigue J., Crawford J.M., Daßler-Plenker J., Guerci P., Huynh C., Knight J.S., Loda M., Looney M.R., McAllister F., Rayes R., Renaud S., Rousseau S., Salvatore S., Schwartz R.E., Spicer J.D., Yost C.C., Weber A., Zuo Y., Egeblad M. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med 2020; 217(6), e20200652, https://doi.org/10.1084/jem.20200652.
49. Yi Y., Lagniton P.N.P., Ye S., Li E., Xu R.H. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci 2020; 16(10): 1753–1766, https://doi.org/10.7150/ijbs.45134.
50. Chen J., Lau Y.F., Lamirande E.W., Paddock C.D., Bartlett J.H., Zaki S.R., Subbarao K. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. J Virol 2010; 84(3): 1289–1301, https://doi.org/10.1128/jvi.01281-09.
51. Yang Y., Xiong Z., Zhang S., Yan Y., Nguyen J., Ng B., Lu H., Brendese J., Yang F., Wang H., Yang X.F. Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J 2005; 392(Pt 1): 135–143, https://doi.org/10.1042/bj20050698.
52. Cron R.Q., Chatham W.W. The rheumatologist’s role in COVID-19. J Rheumato 2020; 47(5): 639–642, https://doi.org/10.3899/jrheum.200334.
53. He Z., Zhao C., Dong Q., Zhuang H., Song S., Peng G., Dwyer D.E. Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets. Int J Infect Dis 2005; 9(6): 323–330, https://doi.org/10.1016/j.ijid.2004.07.014.
54. Chen G., Wu D., Guo W., Cao Y., Huang D., Wang H., Wang T., Zhang X., Chen H., Yu H., Zhang X., Zhang M., Wu S., Song J., Chen T., Han M., Li S., Luo X., Zhao J., Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130(5): 2620–2629, https://doi.org/10.1172/jci137244.
55. Nie S., Zhao X., Zhao K., Zhang Z., Zhang Z., Zhang Z. Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study. medRxiv 2020, https://doi.org/10.1101/2020.03.24.20042283.
56. Zeng Q., Li Y.Z., Huang G., Wu W., Dong S.Y., Xu Y. Mortality of COVID-19 is associated with cellular immune function compared to immune function in Chinese Han population. medRxiv 2020, https://doi.org/10.1101/2020.03.08.20031229.
57. Diao B., Wang C., Tan Y., Chen X., Liu Y., Ning L., Chen L., Li M., Liu Y., Wang G., Yuan Z., Feng Z., Zhang Y., Wu Y., Chen Y. Reduction and functional exhaustion of t cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol 2020; 11: 827, https://doi.org/10.3389/fimmu.2020.00827.
58. Thevarajan I., Nguyen T.H.O., Koutsakos M., Druce J., Caly L., van de Sandt C.E., Jia X., Nicholson S., Catton M., Cowie B., Tong S.Y.C., Lewin S.R., Kedzierska K. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 2020; 26(4): 453–455, https://doi.org/10.1038/s41591-020-0819-2.
59. Liu B., Han J., Cheng X., Yu L., Zhang L., Wang W., Ni L., Wei C., Huang Y., Cheng Z. Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients. medRxiv 2020, https://doi.org/10.1101/2020.03.26.20044768.
60. Chu H., Zhou J., Wong B.H., Li C., Chan J.F., Cheng Z.S., Yang D., Wang D., Lee A.C., Li C., Yeung M.L., Cai J.P., Chan I.H.Y., Ho W.K., To K.K.W., Zheng B.Z., Yao Y., Qin C., Yuen K.Y. Middle East respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J Infect Dis 2016; 213(6): 904–914, https://doi.org/10.1093/infdis/jiv380.
61. Wan S., Yi Q., Fan S., Lv J., Zhang X., Guo L., Lang C., Xiao Q., Xiao K., Yi Z., Qiang M., Xiang J., Zhang B., Chen Y. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv 2020, https://doi.org/10.1101/2020.02.10.20021832.
62. Kamphuis E., Junt T., Waibler Z., Forster R., Kalinke U. Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. Blood 2006; 108(10): 3253–3261, https://doi.org/10.1182/blood-2006-06-027599.
63. Shiow L.R., Rosen D.B., Brdicková N., Xu Y., An J., Lanier L.L., Cyster J.G., Matloubian M. CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 2006; 440(7083): 540–544, https://doi.org/10.1038/nature04606.
64. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8(4): 420–422, https://doi.org/10.1016/s2213-2600(20)30076-x.
65. Tian S., Xiong Y., Liu H., Niu L., Guo J., Liao M., Xiao S.Y. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020; 33(6): 1007–1014, https://doi.org/10.1038/s41379-020-0536-x.
66. Walter J.M., Helmin K.A., Abdala-Valencia H., Wunderink R.G., Singer B.D. Multidimensional assessment of alveolar T cells in critically ill patients. JCI Insight 2018; 3(17): e123287, https://doi.org/10.1172/jci.insight.123287.
67. Lei L., Qian H., Yang X., Zhou X., Zhang X., Zhang D., Dai T., Guo R., Shi L., Cheng Y., Zhang B., Hu J., Guo Y. The phenotypic changes of γδ T cells in COVID-19 patients. J Cell Mol Med 2020, 24(19): 11603–11606, https://doi.org/10.1111/jcmm.15620.
68. Ni L., Ye F., Chen M.L., Feng Y., Deng Y.Q., Zhao H., Wei P., Ge J., Gou M., Li X., Sun L., Cao T., Wang P., Zhou C., Zhang R., Liang P., Guo H., Wang X., Qin C.F., Chen F., Dong C. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity 2020; 52(6): 971-977.е3, https://doi.org/10.1016/j.immuni.2020.04.023.
69. Zheng H.Y., Zhang M., Yang C.X., Zhang N., Wang X.C., Yang X.P., Dong X.Q., Zheng Y.T. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol 2020; 17(5): 541–543, https://doi.org/10.1038/s41423-020-0401-3.
70. Weiskopf D., Schmitz K.S., Raadsen M.P., Grifoni A., Okba N.M.A., Endeman H., van den Akker J.P.C., Molenkamp R., Koopmans M.P.G., van Gorp E.C.M., Haagmans B.L., de Swart R.L., Sette A., de Vries R.D. Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome. Sci Immunol 2020; 5(48), https://doi.org/10.1101/2020.04.11.20062349.
71. Zhang G., Nie S., Zhang Z., Zhang Z. Longitudinal change of severe acute respiratory syndrome coronavirus 2 antibodies in patients with coronavirus disease 2019. J Infect Dis 2020; 222(2): 183–188, https://doi.org/10.1093/infdis/jiaa229.
72. Huang A.T., Garcia-Carreras B., Hitchings M.D.T., Yang B., Katzelnick L., Rattigan S.M., Borgert B., Moreno C., Solomon B.D., Rodriguez-Barraquer I., Lessler J., Salje H., Burke D., Wesolowski A., Cummings D.A.T. A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. Nat Commun 2020; 11(1): 4704, https://doi.org/10.1038/s41467-020-18450-4.
73. Yuan M., Liu H., Wu N.C., Wilson I.A. Recognition of the SARS-CoV-2 receptor binding domain by neutralizing antibodies. Biochem Biophys Res Commun 2021; 538: 192–203, https://doi.org/10.1016/j.bbrc.2020.10.012.
74. To K.K., Tsang O.T., Leung W.S., Tam A.R., Wu T.C., Lung D.C., Yip C.C.Y., Cai J.P., Chan J.M.C., Chik T.S.H., Lau D.P.L., Choi C.Y.C., Chen L.L., Chan W.M., Chan K.-H., Ip J.D., Ng A.C.K., Poon R.W.S., Luo C.T., Cheng V.C.C., Chan J.F.W., Hung I.F.N., Chen Z., Chen H., Yuen K.Y. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 2020; 20(5): 565–574, https://doi.org/10.1016/s1473-3099(20)30196-1.
75. Wu F., Wang A., Liu M., Wang Q., Chen J., Xia S., Ling Y., Zhang Y., Xun J., Lu L., Jiang S., Lu H., Wen Y., Huang J. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv 2020, https://doi.org/10.1101/2020.03.30.20047365.
76. Liu W., Fontanet A., Zhang P.H., Zhan L., Xin Z.T., Baril L., Tang F., Lv H., Cao W.H. Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome. J Infect Dis 2006; 193(6): 792–795, https://doi.org/10.1086/500469.
77. Alshukairi A.N., Khalid I., Ahmed W.A., Dada A.M., Bayumi D.T., Malic L.S., Althawadi S., Ignacio K., Alsalmi H.S., Al-Abdely H.M., Wali G.Y., Qushmaq I.A., Alraddadi B.M., Perlman S. Antibody response and disease severity in healthcare worker MERS survivors. Emerg Infect Dis 2016; 22(6): 1113–1115, https://doi.org/10.3201/eid2206.160010.
78. Long Q.X., Liu B.Z. Deng H.J., Wu G.C., Deng K., Chen Y.K., Liao P., Qiu J.F., Lin Y., Cai X.F., Wang D.Q., Hu Y., Ren J.H., Tang N., Xu Y.Y., Yu L.H., Mo Z., Gong F., Zhang X.L., Tian W.G., Hu L., Zhang X.X., Xiang J.L., Du H.X., Liu H.W., Lang C.H., Luo X.H., Wu S.B., Cui X.P., Zhou Z., Zhu M.M., Wang J., Xue C.J., Li X.F., Wang L., Li Z.J., Wang K., Niu C.C., Yang Q.J., Tang X.J., Zhang Y., Liu X.M., Li J.J., Zhang D.C., Zhang F., Liu P., Yuan J., Li Q., Hu J.L., Chen J., Huang A.L. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020; 26(6): 845–848, https://doi.org/10.1038/s41591-020-0897-1.
79. Guo L., Ren L., Yang S., Xiao M., Chang D., Yang F., Dela Cruz C.S., Wang Y., Wu C., Xiao Y., Zhang L., Han L., Dang S., Xu Y., Yang Q.W., Xu S.Y., Zhu H.D., Xu Y.C., Jin Q., Sharma L., Wang L., Wang J. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis 2020; 71(15): 778–785, https://doi.org/10.1093/cid/ciaa310.
80. Wölfel R., Corman V.M., Guggemos W., Seilmaier M., Zange S., Müller M.A., Niemeyer D., Jones T.C., Vollmar P., Rothe C., Hoelscher M., Bleicker T., Brünink S., Schneider J., Ehmann R., Zwirglmaier K., Drosten C., Wendtner C. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581(7809): 465–469, https://doi.org/10.1038/s41586-020-2196-x.
81. Lou B., Li T.D., Zheng S.F., Su Y.Y., Li Z.Y., Liu W., Yu F., Ge S.X., Zou Q.D., Yuan Q., Lin S., Hong C.M., Yao X.Y., Zhang X.J., Wu D.H., Zhou G.L., Hou W.H., Li T.T., Zhang Y.L., Zhang S.Y., Fan J., Zhang J., Xia N.S., Chen Y. Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset. Eur Respir J 2020; 56(2): 2000763, https://doi.org/10.1183/13993003.00763-2020.
82. Fafi-Kremer S., Bruel T., Madec Y., Grant R., Tondeur L., Grzelak L., Staropoli I., Anna F., Souque F., Fernandes-Pellerin S., Jolly N., Renaudat C., Ungeheuer M.-N., Schmidt-Mutter C., Collongues N., Bolle A., Velay A., Lefebvre N., Mielcarek M., Meyer N., Rey D., Charneau P., Hoen B., De Seze J., Schwartz O., Fontanet A. Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France. EBioMedicine 2020; 59: 102915, https://doi.org/10.1016/j.ebiom.2020.102915.
83. Okba N.M.A., Müller M.A., Li W., Wang C., GeurtsvanKessel C.H., Corman V.M., Lamers M.M., Sikkema R.S., de Bruin E., Chandler F.D., Yazdanpanah Y., Hingrat Q.L., Descamps D., Houhou-Fidouh N., Reusken C.B.E.M., Bosch B.J., Drosten C., Koopmans M.P.G., Haagmans B.L. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients. Emerg Infect Dis 2020; 26(7): 1478–1488, https://doi.org/10.3201/eid2607.200841.
84. Marklund E., Leach S., Axelsson H., Nyström K., Norder H., Bemark M., Angeletti D., Lundgren A., Nilsson S., Andersson L.M., Yilmaz A., Lindh M., Liljeqvist J.Å., Gisslén M. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders. PLoS One 2020; 15(10): e0241104, https://doi.org/10.1371/journal.pone.0241104.
85. Pinto D., Park Y.J., Beltramello M., Walls A.C., Tortorici M.A., Bianchi S., Jaconi S., Culap K., Zatta F., De Marco A., Peter A., Guarino B., Spreafico R., Cameroni E., Case J.B., Chen R.E., Havenar-Daughton C., Snell G., Telenti A., Virgin H.W., Lanzavecchia A., Diamond M.S., Fink K., Veesler D., Corti D. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 2020; 583(7815): 290–295, https://doi.org/10.1038/s41586-020-2349-y.
86. Long Q.X., Tang X.J., Shi Q.L., Li Q., Deng H.J., Yuan J., Hu J.L., Xu W., Zhang Y., Lv F.J., Su K., Zhang F., Gong J., Wu B., Liu X.M., Li J.J., Qiu J.F., Chen J., Huang A.L. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020; 26(8): 1200–1204, https://doi.org/10.1038/s41591-020-0965-6.
87. Wajnberg A., Amanat A., Firpo A., Altman D.R., Bailey M.J., Mansour M., McMahon M., Meade P., Mendu D.R., Muellers K., Stadlbauer D., Stone K., Strohmeier S., Aberg J., Reich D.L., Krammer F., Cordon-Cardo C. SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months. medRxiv 2020, https://doi.org/10.1101/2020.07.14.20151126.
88. Xiao A.T., Gao C., Zhang S. Profile of specific antibodies to SARS-CoV-2: the first report. J Infect 2020; 81(1): 147–178, https://doi.org/10.1016/j.jinf.2020.03.012.
89. Cervia C., Nilsson J., Zurbuchen Y., Valaperti A., Schreiner J., Wolfensberger A., Raeber M.E., Adamo S., Weigang S., Emmenegger M., Hasler S., Bosshard P.P., De Cecco E., Bächli E., Rudiger A., Stüssi-Helbling M., Huber L.C., Zinkernagel A.S., Schaer D.J., Aguzzi A., Kochs G., Held U., Probst-Müller E., Rampini S.K., Boyman O. Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol 2021; 147(2): 545-557.e9, https://doi.org/10.1016/j.jaci.2020.10.040.
90. Zhao J., Yuan Q., Wang H., Liu W., Liao X., Su Y., Wang X., Yuan J., Li T., Li J., Qian S., Hong C., Wang F., Liu Y., Wang Z., He Q., Li Z., He B., Zhang T., Fu Y., Ge S., Liu L., Zhang J., Xia N., Zhang Z. Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clin Infect Dis 2020; 71(16): 2027–2034, https://doi.org/10.1093/cid/ciaa344.
91. Zeng F., Dai C., Cai P., Wang J., Xu L., Li J., Hu G., Wang Z., Zheng F., Wang L. A comparison study of SARS-CoV-2 IgG antibody between male and female COVID-19 patients: a possible reason underlying different outcome between sex. J Med Virol 2020; 92(10): 2050–2054, https://doi.org/10.1002/jmv.25989.
92. Davoudi-Monfared E., Rahmani H., Khalili H., Hajiabdolbaghi M., Salehi M., Abbasian L., Kazemzadeh H., Yekaninejad M.S. A randomized clinical trial of the efficacy and safety of interferon beta-1a in treatment of severe COVID-19. Antimicrob Agents Chemother 2020; 64(9): e01061-20, https://doi.org/10.1128/aac.01061-20.
93. Zhou Q., Chen V., Shannon C.P., Wei X.S., Xiang X., Wang X., Wang Z.H., Tebbutt S.J., Kollmann T.R., Fish E.N. Interferon-alpha2b treatment for COVID-19. Front Immunol 2020; 11: 1061, https://doi.org/10.3389/fimmu.2020.01061.
94. Major J., Crotta S., Llorian M., McCabe T.M., Gad H.H., Priestnall S.L., Hartmann R., Wack A. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science 2020; 369(6504): 712–717, https://doi.org/10.1126/science.abc2061.
95. Lazear H.M., Schoggins J.W., Diamond M.S. Shared and distinct functions of type I and type III interferons. Immunity 2019; 50(4): 907–923, https://doi.org/10.1016/j.immuni.2019.03.025.
96. Galani I.E., Triantafyllia V., Eleminiadou E.E., Koltsida O., Stavropoulos A., Manioudaki M., Thanos D., Doyle S.E., Kotenko S.V., Thanopoulou K., Andreakos E. Interferon-λ mediates non-redundant front-line antiviral protection against influenza virus infection without compromising host fitness. Immunity 2017; 46(5): 875–890.e6, https://doi.org/10.1016/j.immuni.2017.04.025.
97. de Groen R.A., Boltjes A., Hou J., Liu B.S., McPhee F., Friborg J., Janssen H.L.A., Boonstra A. IFN-λ-mediated IL-12 production in macrophages induces IFN-γ production in human NK cells. Eur J Immunol 2015; 45(1): 250–259, https://doi.org/10.1002/eji.201444903.
98. Broggi A., Ghosh S., Sposito B., Spreafico R., Balzarini F., Lo Cascio A., Clementi N., De Santis M., Mancini N., Granucci F., Zanoni I. Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science 2020; 369(6504): 706–712, https://doi.org/10.1126/science.abc3545.
99. Market M., Angka L., Martel A.B., Bastin D., Olanubi O., Tennakoon G., Boucher D.M., Ng J., Ardolino M., Auer R.C. Flattening the COVID-19 curve with natural killer cell based immunotherapies. Front Immunol 2020; 11: 1512, https://doi.org/10.3389/fimmu.2020.01512.
100. Cao Z., Liu L., Du L., Zhang C., Jiang S., Li T., He Y. Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients. Virol J 2010; 7: 299, https://doi.org/10.1186/1743-422x-7-299.
101. Zhu Z., Chakraborti S., He Y., Roberts A., Sheahan T., Xiao X., Hensley L.E., Prabakaran P., Rockx B., Sidorov I.A., Corti D., Vogel L., Feng Y., Kim J.Q., Wang L.F., Baric R., Lanzavecchia A., Curtis K.M., Nabel G.J., Subbarao K., Jiang S., Dimitrov D.S. Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proc Natl Acad Sci U S A 2007; 104(29): 12123–12128, https://doi.org/10.1073/pnas.0701000104.
102. Ying T., Li H., Lu L., Dimitrov D.S., Jiang S. Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections. Microbes Infect 2015; 17(2): 142–148, https://doi.org/10.1016/j.micinf.2014.11.008.
103. Chen X., Li R., Pan Z., Qian C., Yang Y., You R., Zhao J., Liu P., Gao L., Li Z., Huang Q., Xu L., Tang J., Tian Q., Yao W., Hu L., Yan X., Zhou X., Wu Y., Deng K., Zhang Z., Qian Z., Chen Y., Ye L. Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. Cell Mol Immunol 2020; 17(6): 647–649, https://doi.org/10.1038/s41423-020-0426-7.
104. Weinreich D.M., Sivapalasingam S., Norton T., Ali S., Gao H., Bhore R., Musser B.J., Soo Y., Rofail D., Im J., Perry C., Pan C., Hosain R., Mahmood A., Davis J.D., Turner K.C., Hooper A.T., Hamilton J.D., Baum A., Kyratsous C.A., Kim Y., Cook A., Kampman W., Kohli A., Sachdeva Y., Graber X., Kowal B., DiCioccio T., Stahl N., Lipsich L., Braunstein N., Herman G., Yancopoulos G.D.; Trial Investigators. REGN-COV2, a neutralizing antibody cocktail, in outpatients with COVID-19. N Engl J Med 2020; 384(3): 238–251, https://doi.org/10.1056/nejmoa2035002.
105. Marano G., Vaglio S., Pupella S., Facco G., Catalano L., Liumbruno G.M., Grazzini G. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus 2016; 14(2): 152–157, https://doi.org/10.2450/2015.0131-15.
106. Devasenapathy N., Ye Z., Loeb M., Fang F., Najafabadi B.T., Xiao Y., Couban R., Bégin P., Guyatt G. Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis. CMAJ 2020; 192(27): E745–E755, https://doi.org/10.1503/cmaj.200642.
107. Piechotta V., Chai K.L., Valk S.J., Doree C., Monsef I., Wood E.M., Lamikanra A., Kimber C., McQuilten Z., So-Osman C., Estcourt L.J., Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Сochrane Database Syst Rev 2020; 7(7): CD013600, https://doi.org/10.1002/14651858.cd013600.pub2.
108. Shen C., Wang Z., Zhao F., Yang Y., Li J., Yuan J., Wang F., Li D., Yang M., Xing L., Wei J., Xiao H., Yang Y., Qu J., Qing L., Chen L., Xu Z., Peng L., Li Y., Zheng H., Chen F., Huang K., Jiang Y., Liu D., Zhang Z., Liu Y., Liu L. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323(16): 1582–1589, https://doi.org/10.1001/jama.2020.4783.
109. Duan K., Liu B., Li C., Zhang H., Yu T., Qu J., Zhou M., Chen L., Meng S., Hu Y., Peng C., Yuan M., Huang J., Wang Z., Yu J., Gao X., Wang D., Yu X., Li L., Zhang J., Wu X., Li B., Xu Y., Chen W., Peng Y., Hu Y., Lin L., Liu X., Huang S., Zhou Z., Zhang L., Wang Y., Zhang Z., Deng K., Xia Z., Gong Q., Zhang W., Zheng X., Liu Y., Yang H., Zhou D., Yu D., Hou J., Shi Z., Chen S., Chen Z., Zhang X., Yang X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020; 117(7): 9490–9496, https://doi.org/10.1073/pnas.2004168117.
110. Zhang B., Liu S., Tan T., Huang W., Dong Y., Chen L., Chen Q., Zhang L., Zhong Q., Zhang X., Zou Y., Zhang S. Treatment with convalescent plasma for critically ill patients with severe acute respiratory syndrome coronavirus 2 infection. Chest 2020; 158(1): e9–e13, https://doi.org/10.1016/j.chest.2020.03.039.
111. Cheng Y., Wong R., Soo Y.O.Y., Wong W.S., Lee C.K., Ng M.H.L., Chan P., Wong K.C., Leung C.B., Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005; 24(1): 44–46, https://doi.org/10.1007/s10096-004-1271-9.
112. Luke T.C., Kilbane E.M., Jackson J.L., Hoffman S.L. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006; 145(8): 599–609, https://doi.org/10.7326/0003-4819-145-8-200610170-00139.
113. Chen L., Xiong J., Bao L., Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020; 20(4): 398–340, https://doi.org/10.1016/s1473-3099(20)30141-9.
114. Mair-Jenkins J., Saavedra-Campos M., Baillie J.K., Cleary P., Khaw F.M., Lim W.S., Makki S., Rooney K.D., Nguyen-Van-Tam J.S., Beck C.R.; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis 2015; 211(1): 80–90, https://doi.org/10.1093/infdis/jiu396.
115. Joyner M.J., Carter R.E., Senefeld J.W., Klassen S.A., Mills J.R., Johnson P.W., Theel E.S., Wiggins C.C., Bruno K.A., Klompas A.M., Lesser E.R., Kunze K.L., Sexton M.A., Diaz Soto J.C., Baker S.E., Shepherd J.R.A., van Helmond N., Verdun N.C., Marks P., van Buskirk C.M., Winters J.L., Stubbs J.R., Rea R.F., Hodge D.O., Herasevich V., Whelan E.R., Clayburn A.J., Larson K.F., Ripoll J.G., Andersen K.J., Buras M.R., Vogt M.N.P., Dennis J.J., Regimbal R.J., Bauer P.R., Blair J.E., Paneth N.S., Fairweather D.L., Wright R.S., Casadevall A. Convalescent plasma antibody levels and the risk of death from COVID-19. New Eng J Med 2021; 384(11): 1015–1027, https://doi.org/10.1056/nejmoa2031893.
116. Ahn J.Y., Sohn Y., Lee S.H., Cho Y., Hyun J.H., Baek Y.J., Jeong S.J., Kim J.H., Ku N.S., Yeom J.S., Roh J., Ahn M.Y., Chin B.S., Kim Y.S., Lee H., Yong D., Kim H.O., Kim S., Choi J.Y. Use of convalescent plasma therapy in two COVID-19 patients with acute respiratory distress syndrome in Korea. J Korean Med Sci 2020; 35(14): e149, https://doi.org/10.3346/jkms.2020.35.e149.
117. Pei S., Yuan X., Zhang Z., Yao R., Xie Y., Shen M., Li B., Chen X., Yin M. Convalescent plasma to treat COVID-19: Chinese strategy and experiences. medRxiv 2020, https://doi.org/10.1101/2020.04.07.20056440.
118. Tanne J.H. COVID-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ 2020; 368: m1256, https://doi.org/10.1136/bmj.m1256.
119. Brown B.L., McCullough J. Treatment for emerging viruses: convalescent plasma and COVID-19. Transfus Apher Sci 2020; 59(3): 102790, https://doi.org/10.1016/j.transci.2020.102790.
120. Jamilloux Y., Henry T., Belot A., Viel S., Fauter M., Jammal T.E., Walzer T., François B., Sèvea P. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev 2020; 19(7): 102567, https://doi.org/10.1016/j.autrev.2020.102567.
121. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., Liu L., Shan H., Le C.L., Hui D.S.C., Du B., Li L.J., Zeng G., Yuen K.Y., Chen R.C., Tang C.L., Wang T., Chen P.Y., Xiang J., Li S.Y., Wang J.L., Liang Z.J., Peng Y.X., Wei L., Liu Y., Hu Y.H., Peng P., Wang J.M., Liu J.Y., Chen Z., Li G., Zheng Z.J., Qiu S.Q., Luo J., Ye C.J., Zhu S.Y., Zhong N.S. Clinical characteristics of coronavirus disease 2019 in China. New Engl J Med 2020; 382(18): 1708–1720, https://doi.org/10.1056/nejmoa2002032.
122. Polak S.B., Van Gool I.C., Cohen D., von der Thüsen J.H., van Paassen J. A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression. Mod Pathol 2020; 33(11): 2128–2138, https://doi.org/10.1038/s41379-020-0603-3.
123. Villar J., Ferrando C., Martínez D., Ambrós A., Muñoz T., Soler J.A., Aguilar G., Alba F., González-Higueras E., Conesa L.A., Martín-Rodríguez C., Díaz-Domínguez F.J., Serna-Grande P., Rivas R., Ferreres J., Belda J., Capilla L., Tallet A., Añón J.M., Fernández R.L., González-Martín J.M. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med 2020; 8(3): 267–276, https://doi.org/10.1016/s2213-2600(19)30417-5.
124. Villar J., Confalonieri M., Pastores S.M., Meduri G.U. Rationale for prolonged corticosteroid treatment in the acute respiratory distress syndrome caused by coronavirus disease 2019. Crit Care Explor 2020; 2(4): e0111, https://doi.org/10.1097/cce.0000000000000111.
125. Alijotas-Reig J., Esteve-Valverde E., Belizna C., Selva-O’Callaghan A., Pardos-Gea J., Quintana A., Mekinian A., Anunciacion-Llunell A., Miró-Mur F. Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: a comprehensive review. Autoimmun Rev 2020; 19(7): 102569, https://doi.org/10.1016/j.autrev.2020.102569.
126. Jiang S., Liu T., Hu Y., Li R., Di X., Jin X., Wang Y., Wang K. Efficacy and safety of glucocorticoids in the treatment of severe community-acquired pneumonia: a meta-analysis. Medicine (Baltimore) 2019; 98(26): e16239, https://doi.org/10.1097/md.0000000000016239.
127. Li H., Chen C., Hu F., Wang J., Zhao Q., Gale R.P., Liang Y. Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis. Leukemia 2020; 34(6): 1503–1511, https://doi.org/10.1038/s41375-020-0848-3.
128. Singh A.K., Majumdar S., Singh R., Misra A. Role of corticosteroid in the management of COVID-19: a systemic review and a clinician’s perspective. Diabetes Metab Syndr 2020; 14(5): 971–978, https://doi.org/10.1016/j.dsx.2020.06.054.
129. Veronese N., Demurtas J., Yang L., Tonelli.R., Barbagallo M., Lopalco P., Lagolio E., Celotto S., Pizzol D., Zou L., Tully M.A., Ilie P.C., Trott M., López-Sánchez G.F., Smith L. Use of corticosteroids in coronavirus disease 2019 pneumonia: a systematic review of the literature. Front Med (Lausanne) 2020; 7: 170, https://doi.org/10.3389/fmed.2020.00170.
130. Arabi Y.M., Mandourah Y., Al-Hameed F., Sindi A.A., Almekhlafi G.A., Hussein M.A., Jose J., Pinto R., Al-Omari A., Kharaba A., Almotairi A., Al Khatib K., Alraddadi B., Shalhoub S., Abdulmomen A., Qushmaq I., Mady A., Solaiman O., Al-Aithan A.M., Al-Raddadi R., Ragab A., Balkhy H.H., Al Harthy A., Deeb A.M., Al Mutairi H., Al-Dawood A., Merson L., Hayden F.G., Fowler R.A. Corticosteroid therapy for critically ill patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med 2018; 197(6): 757–767, https://doi.org/10.1164/rccm.201706-1172oc.
131. Russell C.D., Millar J.E., Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473–475, https://doi.org/10.1016/S0140-6736(20)30317-2.
132. Stockman L.J., Bellamy R., Garner P. SARS: systematic review of treatment effects. PLoS Med 2006; 3(9): e343, https://doi.org/10.1371/journal.pmed.0030343.
133. RECOVERY Collaborative Group; Horby P., Lim W.S., Emberson J.R., Mafham M., Bell J.L., Linsell L., Staplin N., Brightling C., Ustianowski A., Elmahi E., Prudon B., Green C., Felton T., Chadwick D., Rege K., Fegan C., Chappell L.C., Faust S.N., Jaki T., Jeffery K., Montgomery A., Rowan K., Juszczak E., Baillie J.K., Haynes R., Landray M.J. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021; 384(8): 693–704, https://doi.org/10.1056/nejmoa2021436.
134. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne J.A.C., Murthy S., Diaz J.V., Slutsky A.S., Villar J., Angus D.C., Annane D., Azevedo L.C.P., Berwanger O., Cavalcanti A.B., Dequin P.F., Du B., Emberson J., Fisher D., Giraudeau B., Gordon A.C., Granholm A., Green C., Haynes R., Heming N., Higgins J.P.T., Horby P., Jüni P., Landray M.J., Le Gouge A., Leclerc M., Lim W.S., Machado F.R., McArthur C., Meziani F., Møller M.H., Perner A., Petersen M.W., Savovic J., Tomazini B., Veiga V.C., Webb S., Marshall J.C. Association between administration of systemic corticosteroids and mortality among critically Ill patients with COVID-19: a meta-analysis. JAMA 2020; 324(13): 1330–1341, https://doi.org/10.1001/jama.2020.17023.
135. World Health Organization. COVID-19 Clinical management: living guidance. URL: https://www.who.int/publications/i/ item/clinical-management-of-covid-19.
136. Alhazzani W., Møller M.H., Arabi Y.M., Loeb M., Gong M.N., Fan E., Oczkowski S., Levy M.M., Derde L., Dzierba A., Du B., Aboodi M., Wunsch H., Cecconi M., Koh Y., Chertow D.S., Maitland K., Alshamsi F., Belley-Cote E., Greco M., Laundy M., Morgan J.S., Kesecioglu J., McGeer A., Mermel L., Mammen M.J., Alexander P.E., Arrington A., Centofanti J.E., Citerio G., Baw B., Memish Z.A., Hammond N., Hayden F.G., Evans L., Rhodes A. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med 2020; 46(5): 854–887, https://doi.org/10.1007/s00134-020-06022-5.
137. van Paassen J., Vos J.S., Hoekstra E.M., Neumann K.M.I., Boot P.C., Arbous S.M. Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Crit Care 2020; 24(1): 696, https://doi.org/10.1186/s13054-020-03400-9.
138. Siddiqi H.K., Mehra M.R. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant 2020; 39(5): 405–407, https://doi.org/10.1016/j.healun.2020.03.012.
139. Chen Y., Feng Z., Diao B., Wang R., Wang G., Wang C., Tan Y., Liu L., Wang C., Liu Y., Yuan Z., Ren L., Wu Y., Chen Y. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes. medRxiv 2020, https://doi.org/10.1101/2020.03.27.20045427.
140. Gong J., Dong H., Xia S.Q., Huang Y.Z., Wang D.K., Zhao Y., Liu W.H., Tu S.H., Zhang M.M., Wang Q., Lu F.E. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19 pneumonia. BMC Infect Dis 2020; 20(1): 963, https://doi.org/10.1186/s12879-020-05681-5.
141. Moore J.B., June C.H. Cytokine release syndrome in severe COVID-19. Science 2020; 368(6490): 473–474, https://doi.org/10.1126/science.abb8925.
142. Coomes E.A., Haghbayan H. Interleukin-6 in COVID-19: a systematic review and meta-analysis. Rev Med Virol 2020; 30(6): 1–9, https://doi.org/10.1101/2020.03.30.20048058.
143. Perrone F., Piccirillo M.C., Ascierto P.A., Salvarani C., Parrella R., Marata A.M., Popoli P., Ferraris L., Marrocco-Trischitta M.M., Ripamonti D., Binda F., Bonfanti P., Squillace N., Castelli F., Muiesan M.L., Lichtner M., Calzetti C., Salerno N.D., Atripaldi L., Cascella M., Costantini M., Dolci G., Facciolongo N.C., Fraganza F., Massari M., Montesarchio V., Mussini C., Negri E.A., Botti G., Cardone C., Gargiulo P., Gravina A., Schettino C., Arenare L., Chiodini P., Gallo C.; TOCIVID-19 investigators, Italy. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. J Transl Med 2020; 18(1): 405, https://doi.org/10.1186/s12967-020-02573-9.
144. Xu X., Han M., Li T., Sun W., Wang D., Fu B., Zhou Y., Zheng X., Yang Y., Li X., Zhang X., Pan A., Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020; 117(20): 10970–10975, https://doi.org/10.1073/pnas.2005615117.
145. Roumier M., Paule R., Groh M., Vallée A., Ackermann F. Interleukin-6 blockade for severe COVID-19. medRxiv 2020, https://doi.org/10.1101/2020.04.20.20061861.
146. Sanofi and Regeneron provide update on U.S. Phase 2/3 adaptive-designed trial in hospitalized COVID-19 patients. URL: https://www.sanofi.com/en/media-room/press- releases/2020/2020-04-27-12-58-00.
147. Временные методические рекомендации. Профи­лак­тика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 9 (26.10.2020). URL: https://static-0.minzdrav.gov.ru/ system/attachments/attaches/000/052/548/ original/МР_COVID-19_%28v.9%29.pdf.
148. Wicks I.P., Roberts A.W. Targeting GM-CSF in inflammatory diseases. Nat Rev Rheumatol 2016; 12(1): 37–48, https://doi.org/10.1038/nrrheum.2015.161.
149. Guo X., Higgs B.W., Bay-Jensen A.C., Wu Y., Karsdal M.A., Kuziora M., Godwood A., Close D., Ryan P.C., Roskos L.K., White W.I. Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis. Rheumatology (Oxford) 2018; 57(1): 175–184, https://doi.org/10.1093/rheumatology/kex383.
150. Spinelli F.R., Conti F., Gadina M. HiJAKing SARS-CoV-2? The potential role of JAK inhibitors in the management of COVID-19. Sci Immunol 2020; 5(47), https://doi.org/10.1126/sciimmunol.abc5367.
151. Tanaka Y., McInnes I.B., Taylor P.C., Byers N.L., Chen L., de Bono S., Issa M., Macias W.L., Rogai V., Rooney T.P., Schlichting D.E., Zuckerman S.H., Emery P. Characterization and changes of lymphocyte subsets in baricitinib-treated patients with rheumatoid arthritis: an integrated analysis. Arthritis Rheumatol 2018; 70(12): 1923–1932, https://doi.org/10.1002/art.40680.
152. Chen I.Y., Moriyama M., Chang M.F., Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol 2019; 10: 50, https://doi.org/10.3389/fmicb.2019.00050.
153. Nieto-Torres J.L., Verdiá-Báguena C., Jimenez-Guardeño J.M., Regla-Nava J.A., Castaño-Rodriguez C., Fernandez-Delgado R., Torres J., Aguilella V.M., Enjuanes L. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 in ammasome. Virology 2015; 485: 330–339, https://doi.org/10.1016/j.virol.2015.08.010.
154. Conti P., Gallenga C.E., Tetè G., Cara A., Ronconi G., Younes A., Toniato E., Ross R., Kritas S.K. How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS- CoV-2) infection and lung inflammation mediated by IL-1. J Biol Regul Homeost Agents 2020; 34(2): 333–338, https://doi.org/10.23812/editorial-conti-2.
155. Tardif J.C., Kouz S., Waters D.D., Bertrand O.F., Diaz R., Maggioni A.P., Pinto F.J., Ibrahim R., Gamra H., Kiwan G.S., Berry C., López-Sendón J., Ostadal P., Koenig W., Angoulvant D., Grégoire J.C., Lavoie M.A., Dubé M.P., Rhainds D., Provencher M., Blondeau L., Orfanos A., L’Allier P.L., Guertin M.C., Roubille F. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 2019; 381(26): 2497–2505, https://doi.org/10.1056/nejmoa1912388.
156. Deftereos S.G., Giannopoulos G., Vrachatis D.A., Siasos G.D., Giotaki S.G., Gargalianos P., Metallidis S., Sianos G., Baltagiannis S., Panagopoulos P., Dolianitis K., Randou E., Syrigos K., Kotanidou A., Koulouris N.G., Milionis H., Sipsas N., Gogos C., Tsoukalas G., Olympios C.D., Tsagalou E., Migdalis I., Gerakari S., Angelidis C., Alexopoulos D., Davlouros P., Hahalis G., Kanonidis I., Katritsis D., Kolettis T., Manolis A.S., Michalis L., Naka K.K., Pyrgakis V.N., Toutouzas K.P., Triposkiadis F., Tsioufis K., Vavouranakis E., Martinèz-Dolz L., Reimers B., Stefanini G.G., Cleman M., Goudevenos J., Tsiodras S., Tousoulis D., Iliodromitis E., Mehran R., Dangas G., Stefanadis C.; GRECCO-19 investigators. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw Open 2020; 3(6): e2013136, https://doi.org/10.1001/jamanetworkopen.2020.13136.
157. Lu Y., Chen J., Xiao M., Li W., Miller D.D. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res 2012; 29(11): 2943–2971, https://doi.org/10.1007/s11095-012-0828-z.
158. Montreal Heart Institute. Colchicine coronavirus SARS-CoV2 trial (COLCORONA) (COVID-19). URL: https://clinicaltrials.gov/ct2/show/nct04322682.
159. Шубникова Е.В., Букатина Т.М, Вельц Н.Ю., Ка­перко Д.А., Кутехова Г.В. Ингибиторы контрольных точек иммунного ответа: новые риски нового класса противоопухолевых средств. Безопасность и риск фармакотерапии 2020; 8(1): 9–22, https://doi.org/10.30895/2312-7821-2020-8-1-9-22.
160. Hamashima R., Uchino J., Morimoto Y., Iwasaku M., Kaneko Y., Yamada T., Takayama K. Association of immune checkpoint inhibitors with respiratory infections: a review. Cancer Treat Rev 2020; 90: 102109, https://doi.org/10.1016/j.ctrv.2020.102109.
161. Kattan J., Kattan C., Assi T. Do checkpoint inhibitors compromise the cancer patients’ immunity and increase the vulnerability to COVID-19 infection? Immunotherapy 2020; 12(6): 351–354, https://doi.org/10.2217/imt-2020-0077.
162. Gatto L., Franceschi E., Nunno V.D., Brandes A.A. Potential protective and therapeutic role of immune checkpoint inhibitors against viral infections and COVID-19. Immunotherapy 2020; 12(15): 1111–1114, https://doi.org/10.2217/imt-2020-0109.
163. Lukomska B., Stanaszek L., Zuba-Surma E., Legosz P., Sarzynska S., Drela K. Challenges and controversies in human mesenchymal stem cell therapy. Stem Cells Int 2019; 9628536, https://doi.org/10.1155/2019/9628536.
164. Shetty A.K. Mesenchymal stem cell infusion shows promise for combating coronavirus (COVID-19)-induced pneumonia. Aging Dis 2020; 11(2): 462–464, https://doi.org/10.14336/ad.2020.0301.
165. Leng Z., Zhu R., Hou W., Feng Y., Yang Y., Han Q., Shan G., Meng F., Du D., Wang S., Fan J., Wang W., Deng L., Shi H., Li H., Hu Z., Zhang F., Gao J., Liu H., Li X., Zhao Y., Yin K., He X., Gao Z., Wang Y., Yang B., Jin R., Stambler I., Lim L.W., Su H., Moskalev A., Cano A., Chakrabarti S., Min K.J., Ellison-Hughes G., Caruso C., Jin K., Zhao R.C. Transplantation of ACE2(-) mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis 2020; 11(2): 216–228, https://doi.org/10.14336/ad.2020.0228.
166. Shu L., Niu C., Li R., Huang T., Wang Y., Huang M., Ji N., Zheng Y., Chen X., Shi L., Wu M., Deng K., Wei J., Wang X., Cao Y., Yan J., Feng G. Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Res Ther 2020; 11(1): 36, https://doi.org/10.1186/s13287-020-01875-5.
167. Tufan A., Avanoğlu Güler A., Matucci-Cerinic M. COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs. Turk J Med Sci 2020; 50(SI-1): 620–632, https://doi.org/10.3906/sag-2004-168.
168. Tregoning J.S., Brown E.S., Cheeseman H.M., Flight K.E., Higham S.L., Lemm N.M., Pierce B.F., Stirling D.C., Wang Z., Pollock K.M. Vaccines for COVID-19. Clin Exp Immunol 2020; 202(2): 162–192, https://doi.org/10.1111/cei.13517.
169. Fu Y., Cheng Y., Wu Y. Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin 2020; 35(3): 266–271, https://doi.org/10.1007/s12250-020-00207-4.
170. Tseng C.T., Sbrana E., Iwata-Yoshikawa N., Newman P.C., Garron T., Atmar R.L., Peters C.J., Couch R.B. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One 2012; 7(4): e35421, https://doi.org/10.1371/journal.pone.0035421.
171. Liu L., Wei Q., Lin Q., Fang J., Wang H., Kwok H., Tang H., Nishiura K., Peng J., Tan Z., Wu T., Cheung K.W., Chan K.H., Alvarez X., Qin C., Lackner A., Perlman S., Yuen K.Y., Chen Z. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 2019; 4(4): e123158, https://doi.org/10.1172/jci.insight.123158.
172. Wan Y., Shang J., Sun S., Tai W., Chen J., Geng Q., He L., Chen Y., Wu J., Shi Z., Zhou Y., Du L., Li F. Molecular mechanism for antibody-dependent enhancement of coronavirus entry. J Virol 2020; 94(5): e02015-19, https://doi.org/10.1128/jvi.02015-19.
173. Rauh L.W., Schmidt R. Measles immunization with killed virus vaccine: serum antibody titers and experience with exposure to measles epidemic. Am J Dis Child 1965; 109: 232–237, https://doi.org/10.1001/archpedi.1965.02090020234007.
174. Kim H.W., Canchola J.G., Brandt C.D., Pyles G., Chanock R.M., Jensen K., Parrott R.H. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969; 89(4): 422–434, https://doi.org/10.1093/oxfordjournals.aje.a120955.
175. Sridhar S., Luedtke A., Langevin E., Zhu M., Bonaparte M., Machabert T., Savarino S., Zambrano B., Moureau A., Khromava A., Moodie Z., Westling T., Mascareñas C., Frago C., Cortés M., Chansinghaku D., Noriega F., Bouckenooghe A., Chen J., Ng S.P., Gilbert P.D., Gurunathan S., DiazGranados C.A. Effect of dengue serostatus on dengue vaccine safety and efficacy. N Engl J Med 2018; 379(4): 327–340, https://doi.org/10.1056/nejmoa1800820.
176. World Health Organization. Draft landscape and tracker of COVID-19 candidate vaccines. 2020. URL: https://www.who.int/publications/m/item/draft-landscape -of-COVID-19-candidate-vaccines.
177. World Health Organization. Status of COVID-19 Vaccines within WHO EUL/PQ evaluation process. URL: https://extranet.who.int/pqweb/sites/default/ files/documents/Status_COVID_VAX_18May2021.pdf.
178. Wang Q., Li C., Zhang Q., Wang T., Li J., Guan W., Yu J., Liang M., Li D. Interactions of SARS coronavirus nucleocapsid protein with the host cell proteasome subunit p42. Virol J 2010; 7: 99, https://doi.org/10.1186/1743-422x-7-99.
179. Oliver S.E., Gargano J.W., Marin M., Wallace M., Curran K.G., Chamberland M., McClung N., Campos-Outcalt D., Morgan R.L., Mbaeyi S., Romero J.R., Talbot H.K., Lee G.M., Bell B.P., Dooling K. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 1922–1924, https://doi.org/10.15585/mmwr.mm6950e2.
180. Laczkó D., Hogan M.J., Toulmin S.A., Hicks P., Lederer K., Gaudette B.T., Castaño D., Amanat F., Muramatsu H., Oguin T.H. III, Ojha A., Zhang L., Mu Z., Parks R., Manzoni T.B., Roper B., Strohmeier S., Tombácz I., Arwood L., Nachbagauer R., Karikó K., Greenhouse J., Pessaint L., Porto M., Putman-Taylor T., Strasbaugh A., Campbell T.A., Lin P.J.C., Tam Y.K., Sempowski G.D., Farzan M., Choe H., Saunders K.O., Haynes B.F., Andersen H., Eisenlohr L.C., Weissman D., Krammer F., Bates P., Allman D., Locci M., Pardi N. A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice. Immunity 2020; 53(4): 724–732.e7, https://doi.org/10.1016/j.immuni.2020.07.019.
181. Mulligan M.J., Lyke K.E., Kitchin N., Absalon J., Gurtman A., Lockhart S., Neuzil K., Raabe V., Bailey R., Swanson K.A., Li P., Koury K., Kalina W., Cooper D., Fontes-Garfias C., Shi P.Y., Türeci Ö., Tompkins K.R., Walsh E.E., Frenck R., Ann R., Falsey A.R., Dormitzer P.R., Gruber W.C., Şahin U., Jansen K.U. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 2020; 586(7830): 589–593, https://doi.org/10.1038/s41586-020-2639-4.
182. Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Pérez Marc G., Moreira E.D., Zerbini C., Bailey R., Swanson K.A., Roychoudhury S., Koury K., Li P., Kalina W.V., Cooper D., Frenck R.W.  Jr., Hammitt L.L., Türeci Ö., Nell H., Schaefer A., Ünal S., Tresnan D.B., Mather S., Dormitzer P.R., Şahin U., Jansen K.U., Gruber W.C.; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med 2020; 383(27): 2603–2615, https://doi.org/10.1056/nejmoa2034577.
183. Folegatti P.M., Ewer K.J., Aley P.K., Angus B., Becker S., Belij-Rammerstorfer S., Bellamy D., Bibi S., Bittaye M., Clutterbuck E.A., Dold C., Faust S.N., Finn A., Flaxman A.L., Hallis B., Heath P., Jenkin D., Lazarus R., Makinson R., Minassian A.M., Pollock K.M., Ramasamy M., Robinson H., Snape M., Tarrant R., Voysey M., Green C., Douglas A.D., Hill A.V.S., Lambe T., Gilbert S.C., Pollard A.J.; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020; 396(10249): 467–478, https://doi.org/10.1016/s0140-6736(20)31604-4.
184. Sadoff J., Gray G., Vandebosch A., Cárdenas V., Shukarev G., Grinsztejn B., Goepfert P.A., Truyers C., Fennema H., Spiessens B., Offergeld K., Scheper G., Taylor K.L., Robb M.L., Treanor J., Barouch D.H., Stoddard J., Ryser M.F., Marovich M.A., Neuzil K.M., Corey L., Cauwenberghs N., Tanner T., Hardt K., Ruiz-Guiñazú J., Le Gars M., Schuitemaker H., Van Hoof J., Struyf F., Douoguih M.; ENSEMBLE Study Group. Safety and efficacy of single-dose Ad26.COV2.S vaccine against COVID-19. N Engl J Med 2021, https://doi.org/10.1056/nejmoa2101544.
185. Corbett K.S., Edwards D., Leist S.R., Abiona O.M., Boyoglu-Barnum S., Gillespie R.A., Himansu S., Schäfer A., Ziwawo C.T., DiPiazza A.T., Dinnon K.H., Elbashir S.M., Shaw C.A., Woods A., Fritch E.J., Martinez D.R., Bock K.W., Minai M., Nagata B.M., Hutchinson G.B., Bahl K., Garcia-Dominguez D., Ma L., Renzi I., Kong W.P., Schmidt S.D., Wang L., Zhang Y., Stevens L.J., Phung E., Chang L.A., Loomis R.J., Altaras N.E., Narayanan E., Metkar M., Presnyak V., Liu C., Louder M.K., Shi W., Leung K., Yang E.S., West A., Gully K.L., Wang N., Wrapp D., Doria-Rose N.A., Stewart-Jones G., Bennett H., Nason M.C., Ruckwardt T.J., McLellan J.S., Denison M.R., Chappell J.D., Moore I.N., Morabito K.M., Mascola J.R., Baric R.S., Carfi A., Graham B.S. SARS-CoV-2 mRNA vaccine development enabled by prototype pathogen preparedness. bioRxiv 2020; 11: 2020.06.11.145920, https://doi.org/10.1101/2020.06.11.145920.
186. Jackson L.A., Anderson E.J., Rouphael N.G., Roberts P.C., Makhene M., Coler R.N., McCullough M.P., Chappell J.D., Denison M.R., Stevens L.J., Pruijssers A.J., McDermott A., Flach B., Doria-Rose N.A., Corbett K.S., Morabito K.M., O’Dell S., Schmidt S.D., Swanson P.A., Padilla M., Mascola J.R., Neuzil K.M., Bennett H., Sun W., Peters E., Makowski M., Albert J., Cross K., Buchanan W., Pikaart-Tautges R., Ledgerwood J.E., Graham B.S., Beigel J.H.; mRNA-1273 Study Group. An mRNA vaccine against SARS-CoV-2 — preliminary report. N Engl J Med 2020; 383(20): 1920–1931, https://doi.org/10.1056/nejmoa2022483.
187. Baden L.R., El Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., Diemert D., Spector S.A., Rouphael N., Creech C.B., McGettigan J., Khetan S., Segall N., Solis J., Brosz A., Fierro C., Schwartz H., Neuzil K., Corey L., Gilbert P., Janes H., Follmann D., Marovich M., Mascola J., Polakowski L., Ledgerwood J., Graham B.S., Bennett H., Pajon R., Knightly C., Leav B., Deng W., Zhou H., Han S., Ivarsson M., Miller J., Zaks T.; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384(5): 403–416, https://doi.org/10.1056/nejmoa2035389.
188. WHO lists additional COVID-19 vaccine for emergency use and issues interim policy recommendations. URL: https://www.who.int/news/item/07-05-2021 -who-lists-additional-covid-19-vaccine-for-emergency- use-and-issues-interim-policy-recommendations.
189. Logunov D.Y., Dolzhikova I.V., Zubkova O.V., Tukhvatulin A.I., Shcheblyakov D.V., Dzharullaeva A.S., Grousova D.M., Erokhova A.S., Kovyrshina A.V., Botikov A.G., Izhaeva F.M., Popova O., Ozharovskaya T.A., Esmagambetov I.B., Favorskaya I.A., Zrelkin D.I., Voronina D.V., Shcherbinin D.N., Semikhin A.S., Simakova Y.V., Tokarskaya E.A., Lubenets N.L., Egorova D.A., Shmarov M.M., Nikitenko N.A., Morozova L.F., Smolyarchuk E.A., Kryukov E.V., Babira V.F., Borisevich S.V., Naroditsky B.S., Gintsburg A.L. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet 2020; 396(10255): 887–897, https://doi.org//10.1016/s0140-6736(20)31866-3.
190. Logunov D.Y., Dolzhikova I.V., Zubkova O.V., Tukhvatulin A.I., Shcheblyakov D.V., Dzharullaeva A.S., Kovyrshina A.V., Lubenets N.L., Grousova D.M., Erokhova A.S., Botikov A.G., Izhaeva F.M., Popova O., Ozharovskaya T.A., Esmagambetov I.B., Favorskaya I.A., Zrelkin D.I., Voronina D.V., Shcherbinin D.N., Semikhin A.S., Simakova Y.V., Tokarskaya E.A., Egorova D.A., Shmarov M.M., Nikitenko N.A., Smolyarchuk E.A., Gushchin V.A., Zyryanov S.K., Borisevich S.V., Naroditsky B.S., Gintsburg A.L.; Gam-COVID-Vac Vaccine Trial Group. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2020; 397(10275): 671–681, https://doi.org/10.1016/s0140-6736(21)00234-8.
191. Рыжиков А.Б., Рыжиков Е.А., Богрянцева М.П., Усова С.В., Даниленко Е.Д., Нечаева Е.А., Пьянков О.В., Пьянкова О.Г., Гудымо А.С., Боднев С.А., Онхонова Г.С., Слепцова Е.С., Кузубов В.И., Рыднюк Н.Н., Гинько З.И., Петров В.Н., Моисеева А.А., Торжкова П.Ю., Пьянков С.А., Трегубчак Т.В., Антонец Д.В., Гаврилова Е.В., Максютов Р.А. Простое слепое плацебо-контролируемое рандомизированное исследование безопасности, реактогенности и иммуногенности вакцины «ЭпиВакКорона» для профилактики COVID-19 на добровольцах в возрасте 18–60 лет (фаза I–II). Инфекция и иммунитет 2021; 11(2): 283–296, https://doi.org/10.15789/2220-7619-ASB-1699.
192. URL: https://covivac.ru/.
193. Лядова И.В., Стариков А.А. COVID-19 и вакцинация БЦЖ: есть ли связь? Инфекция и иммунитет 2020; 10(3): 459–468, https://doi.org/10.15789/2220-7619-cab-1472.
194. Sohrabi Y., Dos Santos J.C., Dorenkamp M., Findeisen H., Godfrey R., Netea M.G., Joosten L.A. Trained immunity as a novel approach against COVID-19 with a focus on Bacillus Calmette–Guérin vaccine: mechanisms, challenges and perspectives. Clin Transl Immunology 2020; 9(12): e1228, https://doi.org/10.1002/cti2.1228.

Lyubavina N.A., Saltsev S.G., Menkov N.V., Tyurikova L.V., Plastinina S.S., Shonia M.L., Tulichev A.A., Milyutina M.Yu., Makarova E.V. Immunological Approaches to the Treatment of Novel Coronavirus Infection (Review). Sovremennye tehnologii v medicine 2021; 13(3): 81, https://doi.org/10.17691/stm2021.13.3.09