antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2020-65-11-12-27-37antibiotics-774Research ArticleОБЗОРЫREVIEWSЦитокиновый шторм при новой коронавирусной инфекции и способы его коррекцииCytokine Storm in the Novel Coronavirus Infection and Methods of its Correctionhttps://orcid.org/0000-0001-5758-8552ЕршовА. В.ErshovA. V.

Ершов Антон Валерьевич — д. м. н. профессор кафедры патофизиологии;

старший научный сотрудник

Москва

https://orcid.org/0000-0002-1700-7757СуроваВ. Д.SurovaV. D.

Сурова Василиса Дмитриевна — студентка 3-го курса

Москва

Moscow

ДолгихВ. Т.DolgikhV. T.

Долгих Владимир Терентьевич — д. м. н., профессор, заслуженный деятель науки РФ, главный научный сотрудник

Москва

Moscow

prof_dolgih@mail.ruДолгихТ. И.DolgikhT. I.

Долгих Татьяна Ивановна — д. м. н., профессор, ведущий эксперт Центра внешнего контроля качества клинических лабораторных исследований

Москва

Moscow

Первый Московский государственный медицинский университет им. И. М. Сеченова (Сеченовский Университет); НИИ общей реаниматологии им. В. А. Неговского ФНКЦ РРРоссияI. M. Sechenov First Moscow State Medical University; V. A. Negovsky Research Institute of General Reanimatology Federal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian FederationПервый Московский государственный медицинский университет им. И. М. Сеченова (Сеченовский Университет)РоссияI. M. Sechenov First Moscow State Medical UniversityRussian FederationНИИ общей реаниматологии им. В. А. Неговского ФНКЦ РРРоссияV. A. Negovsky Research Institute of General Reanimatology Federal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian FederationЦентр внешнего контроля качества клинических лабораторных исследованийРоссияCenter for External Quality Control of Clinical Laboratory ResearchRussian Federation2020130220216511-122737Copyright © ООО «Издательство ОКИ», 20212021ООО «Издательство ОКИ»ООО «Издательство ОКИ»https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNoticehttps://www.antibiotics-chemotherapy.ru/jour/article/view/774

Цель — на основании анализа 80 источников литературы, из которых отечественных 17,4% и зарубежных 82,6%, cо средним импакт-фактором 11,94 (максимальное значение — 74,699), за 2014–2020 гг. выявить роль цитокинового шторма при новой коронавирусной инфекции, возникшей в конце 2019 г. В данном обзоре подробно рассмотрены возможные причины и патогенетические факторы развития синдрома цитокинового шторма при новой коронавирусной инфекции. Раскрыты результаты исследований по использованию различных принципов коррекции цитокинового шторма. Установлено, что причиной поражения лёгких и летального исхода при данной болезни является не само действие вируса, а гиперреакция иммунной системы организма в ответ на него. Ведущая роль в этом процессе принадлежит цитокиновому шторму, в том числе действию IL-6.

The aim of the study was to identify the role of cytokine storm in COVID-19, that emerged at the end of 2019, based on the analysis of 80 publications, including 17.4% Russian and 82.6% foreign publications for 2014–2020 with an average impact factor of 11.94 and a maximum of 74.699. This review includes an in-depth discussion of the possible causes and pathogenetic factors of cytokine storm syndrome development caused by COVID-19. The results of research on the use of various principles of cytokine storm correction are provided. It has been established that lung damage and the development of a fatal outcome are caused not by the virus itself, but by the hyperreaction of the body's immune system. The leading role in this process belongs to the cytokine storm, including the action of IL-6.

новая коронавирусная инфекцияCOVID-19SARS-CoV-2цитокиновый штормшиповидный белокS-белокIL-6антителозависимое усиление инфекцииADEnew coronavirus infectionCOVID-19SARS-CoV-2cytokine stormspike proteinS-proteinIL-6antibody-dependent infection enhancementADEReferencesGorbalenya A.E., Baker S.C., Baric R.S., de Groot R.J., Drosten C, Gulyaeva A.A. et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020; 5: 536–544. doi:10.1038/s41564-020-0695-z.Gorbalenya A.E., Baker S.C., Baric R.S., de Groot R.J., Drosten C, Gulyaeva A.A. et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020; 5: 536–544. doi:10.1038/s41564-020-0695-z.who.int [Internet]. Coronavirus disease 2019 (COVID-19) situation report-37. Geneva: World Health Organization. [доступ от 04.10.2020]. Доступ по ссылке: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20201005-weekly-epi-update-8.pdfwho.int [Internet]. Coronavirus disease 2019 (COVID-19) situation report-37. Geneva: World Health Organization. [доступ от 04.10.2020]. Доступ по ссылке: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20201005-weekly-epi-update-8.pdfLi Q., Guan X., Wu P., Wang X., Zhou L., Tong Y. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. The New England journal of medicine 2020; 382 (13): 1199–1207. doi: 10.1056/NEJMoa2001316.Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. The New England journal of medicine 2020; 382 (13): 1199–1207. doi: 10.1056/NEJMoa2001316.Ziegler C., Allon S., Nyquist S., Mbano I.M., Miao V.N., Tzouanas C.N. 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; 181(5): 1016–1035. doi: 10.1016/j.cell.2020.04.035.Ziegler C., Allon S., Nyquist S., Mbano I.M., Miao V.N., Tzouanas C.N. 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; 181(5): 1016–1035. doi: 10.1016/j.cell.2020.04.035.Wu C., Zheng M. Single-cell RNA expression profiling shows that ACE2, the putative receptor for COVID-2019, has significant expression in nasal and mouth tissue and is co-expressed with TMPRSS2 and not coexpressed with SLC6A19 in the tissues. Research Square 2020. doi: 10.21203/rs.3.rs-16992/v1.Wu C., Zheng M. Single-cell RNA expression profiling shows that ACE2, the putative receptor for COVID-2019, has significant expression in nasal and mouth tissue and is co-expressed with TMPRSS2 and not coexpressed with SLC6A19 in the tissues. Research Square 2020. doi: 10.21203/rs.3.rs-16992/v1.Баклаушев В.П., Кулемзин С.В., Горчаков А.А., Лесняк В.Н., Юсубалиева Г.М., Сотникова А.Г. COVID-19. Этиология, патогенез, диагностика и лечение. Клиническая практика. — 2020. — Т. 11. — № 1. — С. 7–20. doi: 10.17816/clinpract26339.Baklaushev V.P., Kulemzin S.V., Gorchakov A.A., Lesnyak V.N., Yusubalieva G.M., Sotnikova A.G. COVID-19. Aetiology, pathogenethis, diagnosis and treatment. Clinical Practice 2020; 11 (1): 7–20. [in Russian]. doi: 10.17816/clinpract26339.Chu H., Zhou J., Wong B.H., Li C., Chan J.F., Cheng Z-S. et al. 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. doi: 10.1093/infdis/jiv380.Chu H., Zhou J., Wong B.H., Li C., Chan J.F., Cheng Z-S. et al. 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. doi: 10.1093/infdis/jiv380.Wang K., Chen W., Zhou Y-S., Lian J-Q., Zhang Z., Du P. et al. SARSCoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv. 2020. doi: 10.1101/2020.03.14.988345.Wang K., Chen W., Zhou Y-S., Lian J-Q., Zhang Z., Du P. et al. SARSCoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv. 2020. doi: 10.1101/2020.03.14.988345.Zhang M.Y., Zhang Y., Wu X.D., Zhang K., Lin P., Bian H-J. et al. Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum. Blood 2018; 131(10): 1111–1121. doi: 10.1182/blood-2017-08-802918.Zhang M.Y., Zhang Y., Wu X.D., Zhang K., Lin P., Bian H-J. et al. Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum. Blood 2018; 131(10): 1111–1121. doi: 10.1182/blood-2017-08-802918.Seizer P., Gawaz M., May A.E. Cyclophilin A and EMMPRIN (CD147) in cardiovascular diseases. Cardiovascular Res 2014; 102 (1):17–23. doi: 10.1093/cvr/cvu035Seizer P., Gawaz M., May A.E. Cyclophilin A and EMMPRIN (CD147) in cardiovascular diseases. Cardiovascular Res 2014; 102 (1):17–23. doi: 10.1093/cvr/cvu035Kanyenda L.J., Verdile G., Martins R., Meloni B.P., Chieng J., Mastaglia F. et al. Is cholesterol and amyloid-β stress induced CD147 expression a protective response? Evidence that extracellular cyclophilin a mediated neuroprotection is reliant on CD147. J Alzheimer's Dis 2014; 9 (3): 545–556. doi: 10.3233/JAD-131442Kanyenda L.J., Verdile G., Martins R., Meloni B.P., Chieng J., Mastaglia F. et al. Is cholesterol and amyloid-β stress induced CD147 expression a protective response? Evidence that extracellular cyclophilin a mediated neuroprotection is reliant on CD147. J Alzheimer's Dis 2014; 9 (3): 545–556. doi: 10.3233/JAD-131442Bian H., Zheng Z-H., Wei D., Zhang Z., Kang W-X., Hao C-Q. et al. Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial. MedRxiv 2020. doi: 10.1101/2020.03.21.20040691.Bian H., Zheng Z-H., Wei D., Zhang Z., Kang W-X., Hao C-Q. et al. Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial. MedRxiv 2020. doi: 10.1101/2020.03.21.20040691.Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497–506. doi: 10.1016/S0140-6736(20)30183-5.Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497–506. doi: 10.1016/S0140-6736(20)30183-5.Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395 (10223): 507–513. doi: 10.1016/S0140-6736(20)30211-7.Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395 (10223): 507–513. doi: 10.1016/S0140-6736(20)30211-7.Wang Z., Yang B., Li Q., Wen L., Zhang R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan. China. Clin Infect Dis 2020; 71 (15): 769–777. doi: 10.1093/cid/ciaa272.Wang Z., Yang B., Li Q., Wen L., Zhang R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan. China. Clin Infect Dis 2020; 71 (15): 769–777. doi: 10.1093/cid/ciaa272.Liu Y., Zhang C., Huang F., Yang Y., Wang F., Yuan J. et al. Elevated plasma level of selective cytokines in COVID-19 patients reflect viral load and lung injury. Nat Sci Rev 2020; 7 (6): 1003–1011. doi: 10.1093/nsr/nwaa037.Liu Y., Zhang C., Huang F., Yang Y., Wang F., Yuan J. et al. Elevated plasma level of selective cytokines in COVID-19 patients reflect viral load and lung injury. Nat Sci Rev 2020; 7 (6): 1003–1011. doi: 10.1093/nsr/nwaa037.Liu J., Li S., Liu J., Liang B., Wang X., Whang H. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102789. doi: 10.1016/j.ebiom.2020.102763.Liu J., Li S., Liu J., Liang B., Wang X., Whang H. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102789. doi: 10.1016/j.ebiom.2020.102763.Xu B., Fan C.Y., Wang A.L., Zou Y.L., Yu Y.H., He C. et al. Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China. J Infection 2020; 81 (1): 51–60. doi: 10.1016/j.jinf.2020.04.012.Xu B., Fan C.Y., Wang A.L., Zou Y.L., Yu Y.H., He C. et al. Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China. J Infection 2020; 81 (1): 51–60. doi: 10.1016/j.jinf.2020.04.012.Гребенчиков О.А., Забелина Т.С., Филипповская Ж.С., Герасименко О.Н., Плотников Е.Ю., Лихванцев В.В. Молекулярные механизмы окислительного стресса. Вестник интенсивной терапии. — 2016. — № 3. — С. 13–21.Grebenchikov O.A., Zabelina T.S., Filippovskaya Z.S., Gerasimenko O.N., Plotnikov E.Y., Likhvantsev V.V. Molekulyarnye mekhanizmy okislitel'nogo stressa. Vestnik Intensivnoi Terapii 2016; 3: 13–21. [in Russian]Ярыгина Е.Г., Прокопьева В.Д., Бохан Н.А. Окислительный стресс и его коррекция карнозином. Успехи современного естествознания. — 2015. — № 4. — С. 106–113.Yarygina E.G., Prokop'eva V.D., Bokhan N.A. Oxidative stress and its correction by carnosine. Uspekhi Sovremennogo Estestvoznaniya 2015; 4: 106–113 [in Russian]Зиновкин Р.А., Гребенчиков О.А. Активация транскрипционного фактора NRF2 как подход к предотвращению цитокинового шторма при COVID19. Биохимия. — 2020. — Т. 85. — № 4. — С. 978–983. doi: 10.31857/S0320972520070118.Zinovkin RA., Grebenchikov O.A. Aktivatsiya transkriptsionnogo faktora NRF2 kak podkhod k predotvrashcheniyu tsitokinovogo shtorma pri COVID19. Biochemistry 2020; 85 (4): 978–983. [in Russian] doi: 10.31857/S0320972520070118.Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8 (4): 420–422. doi: 10.1016/S2213-2600(20)30076-X.Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8 (4): 420–422. doi: 10.1016/S2213-2600(20)30076-X.Fox S.E., Akmatbekov A., Harbert J.L., Li G., Brown J.Q., Heide R.S. et al. Pulmonary and cardiac pathology in COVID-19: The first autopsy series from New Orleans. Lancet Respir Med 2020; 8 (7): 681–686. doi: 10.1101/2020.04.06.20050575.Fox S.E., Akmatbekov A., Harbert J.L., Li G., Brown J.Q., Heide R.S. et al. Pulmonary and cardiac pathology in COVID-19: The first autopsy series from New Orleans. Lancet Respir Med 2020; 8 (7): 681–686. doi: 10.1101/2020.04.06.20050575.Насонов Е.Л. Иммунопатология и иммунофармакотерапия коронавирусной болезни 2019 (COVID-19): фокус на интерлейкин 6. Научно-практическая ревматология. — 2020. — Т. 58. — № 3. — С. 245–261. doi: 10.14412/1995-4484-2020-245-261.Nasonov E.L. Immunopathology and immunopharmacotherapy of coronavirus disease 2019 (COVID-19): focus on interleukin 6. Nauchno-Prakticheskaya Revmatologiya 2020; 58 (3): 245–261 [in Russian] doi: 10.14412/1995-4484-2020-245-261.Siu K.L., Chan C.P., Kok K.H., Woo P.С., Jin D.Y. Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. Cellul Mol Immunol 2014; 11: 141–149. doi: 10.1038/cm 2013.61.Siu K.L., Chan C.P., Kok K.H., Woo P.С., Jin D.Y. Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. Cellul Mol Immunol 2014; 11: 141–149. doi: 10.1038/cm 2013.61.biochemmack.ru [интернет]. Цитокиновый шторм при различных вариантах течения COVID-19 [доступ от 04.10.2020]. Доступ по ссылке: https://www.biochemmack.ru/news/tsitokinovyy_shtorm_pri_razlichnykh_variantakh_techeniya_covid_19_/biochemmack.ru[internet]. Tsitokinovyj shtorm pri razlichnykh variantakh techeniya COVID-19 [dostup ot 04.10.2020]. Dostup po ssylke: https://www.biochemmack.ru/news/tsitokinovyy_shtorm_pri_razlichnykh_variantakh_techeniya_covid_19_/ [in Russian]Tay M.Z., Poh C.M., Renia L., MacAry P.A., Ng L.F. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020; 20: 363–374. doi: 10.1038/s41577-020-0311-8.Tay M.Z., Poh C.M., Renia L., MacAry P.A., Ng L.F. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020; 20: 363–374. doi: 10.1038/s41577-020-0311-8.Moore J.B., June C.H. Cytokine release syndrome in severe COVID-19. Science 2020; 368 (6490): 473–474. doi: 10.1126/science.abb8925.Moore J.B., June C.H. Cytokine release syndrome in severe COVID-19. Science 2020; 368 (6490): 473–474. doi: 10.1126/science.abb8925.Lui T., Zhang J., Yang Y., Ma H., Li Z., Zhang J. et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med 2020; 12 (7): e12421. doi: 10.15252/emmm.202012421.Lui T., Zhang J., Yang Y., Ma H., Li Z., Zhang J. et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med 2020; 12 (7): e12421. doi: 10.15252/emmm.202012421.Ruan Q., Yang K., Wang W., Jiang L., Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Inten Care Med 2020;.46 (5): 846–848. doi: 10.1007/s00134-020-05991.Ruan Q., Yang K., Wang W., Jiang L., Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Inten Care Med 2020;.46 (5): 846–848. doi: 10.1007/s00134-020-05991.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. doi: 10.3389/fimmu.2020.00827.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. doi: 10.3389/fimmu.2020.00827.Coomes E.A., Haghbayan H. Interleukin-6 in COVID-19: a systemic review and meta-analysis. MedRxiv 2020. doi: 10.1101/2020.03.30.200448058.Coomes E.A., Haghbayan H. Interleukin-6 in COVID-19: a systemic review and meta-analysis. MedRxiv 2020. doi: 10.1101/2020.03.30.200448058.Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Internal Med 2020; 180 (1): 934–943. doi: 10.1001/jamainternmed.2020.0994.Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Internal Med 2020; 180 (1): 934–943. doi: 10.1001/jamainternmed.2020.0994.Wenjun W., Xiaoqing L., Wu S., Chen S., Li Y., Nong N. et al. The definition and risk of cytokine release syndrome-like in 11 COVID-19 infected pneumonia critically ill patients: disease characteristics and retrospective analysis. J Infect Dis 2020; 222 (9): 1444–1451. doi: 10.1093/infdis/jiaa387.Wenjun W., Xiaoqing L., Wu S., Chen S., Li Y., Nong N. et al. The definition and risk of cytokine release syndrome-like in 11 COVID-19 infected pneumonia critically ill patients: disease characteristics and retrospective analysis. J Infect Dis 2020; 222 (9): 1444–1451. doi: 10.1093/infdis/jiaa387.Herold T., Jurinovic V., Arnreixh C., Lipworth B.J., Hellmuth J.C., Bergwelt-Baildon M. et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol 2020; 146 (1): 128–136. doi: 10.1016/j.jaci.2020.05.008.Herold T., Jurinovic V., Arnreixh C., Lipworth B.J., Hellmuth J.C., Bergwelt-Baildon M. et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol 2020; 146 (1): 128–136. doi: 10.1016/j.jaci.2020.05.008.Нечипуренко Ю.Д., Анашкина А.А., Матвеева О.В. Изменение антигенных детерминант S-белка вируса SARS-CoV-2 как возможная причина антителозависимого усиления инфекции и цитокинового шторма 2020 г. Биофизика. — 2020. — Т. 65. — № 4. — С. 824–832. doi: 10.31857/S0006302920040262.Nechipurenko Y.D., Anashkina A.A., Matveeva O.V. Change of antigenic determinants of SARS-CoV-2 virus S-protein as a possible cause of antibody-dependent enhancement of virus infection and cytokine storm. Biophysics 2020; 65 (4): 824–832. [in Russian] doi: 10.31857/S0006302920040262.Wan Y., Shang J., Sun S., Tai W., Chen J., Geng Q. et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virology 2020; 94 (5): 2015–2019. doi: 10.1128/JVI.02015-19.Wan Y., Shang J., Sun S., Tai W., Chen J., Geng Q. et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virology 2020; 94 (5): 2015–2019. doi: 10.1128/JVI.02015-19.Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z. et al. Retracted article: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cellular & Molecul Immunol 2020; 17 (8): 1–3. doi: 10.1038/s41423-020-0424-9.Wang X., Xu W., Hu G., Xia S., Sun Z., Liu Z. et al. Retracted article: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cellular & Molecul Immunol 2020; 17 (8): 1–3. doi: 10.1038/s41423-020-0424-9.Bosteels C., Neyt K., Vanheerswynghels M., van Helden M.J., Sichien D., Debeuf N. et al. Inflammatory type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity 2020; 52 (6): 1039–1056. doi: 10.1016/j.immuni.2020.04.005.Bosteels C., Neyt K., Vanheerswynghels M., van Helden M.J., Sichien D., Debeuf N. et al. Inflammatory type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity 2020; 52 (6): 1039–1056. doi: 10.1016/j.immuni.2020.04.005.Wan Y., Shang J., Sun S., Tai W., Chen J., Geng Q. et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol 2020; 94 (5): 2015–2019. doi: 10.1128/JVI.02015-19.Wan Y., Shang J., Sun S., Tai W., Chen J., Geng Q. et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol 2020; 94 (5): 2015–2019. doi: 10.1128/JVI.02015-19.Супотницкий М. В. Слепые пятна вакцинологии. М.: Русская панорама, 2016. / Supotnitskii M.V. Slepye pyatna vaktsinologii. Moscow: Russkaya Panorama, 2016. [in Russian]Супотницкий М. В. Слепые пятна вакцинологии. М.: Русская панорама, 2016. / Supotnitskii M.V. Slepye pyatna vaktsinologii. Moscow: Russkaya Panorama, 2016. [in Russian]Супотницкий М.В. Неугодная иммунология. Актуальная инфектология. — 2016. — № 2 (11). — С.73–93. / Supotnitskii M.V. Unwanted immunology. Actual Infectol 2016; 2 (11): 73–93. [in Russian]Супотницкий М.В. Неугодная иммунология. Актуальная инфектология. — 2016. — № 2 (11). — С.73–93. / Supotnitskii M.V. Unwanted immunology. Actual Infectol 2016; 2 (11): 73–93. [in Russian]Yip M.S., Leung H.L., Li P.H., Cheung C.Y., Dutry I., Li D. et al. Antibodydependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS. Hong Kong Medical Journal 2016; 22 (3): 25–31.Yip M.S., Leung H.L., Li P.H., Cheung C.Y., Dutry I., Li D. et al. Antibodydependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS. Hong Kong Medical Journal 2016; 22 (3): 25–31.Wang Q., Zhang L., Kuwahara K., Li L., Liu Z., Li T. et al. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates. ACS Infect Dis 2016; 2 (5): 361–376. doi: 10.1021/acsinfecdis.6b00006.Wang Q., Zhang L., Kuwahara K., Li L., Liu Z., Li T. et al. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates. ACS Infect Dis 2016; 2 (5): 361–376. doi: 10.1021/acsinfecdis.6b00006.Jaume M., Yip M.S., Leung N.L., Cheung C.Y., Li H.P., Yeung Lee H.H. et al. Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus. Virology J 2014; 11 (82).Jaume M., Yip M.S., Leung N.L., Cheung C.Y., Li H.P., Yeung Lee H.H. et al. Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus. Virology J 2014; 11 (82).Jia Y., Shen G., Zhang Y., Huang K-S., Ho H-Y., Hor W.S. et al. Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity. BioRxiv 2020. doi: 10.1101/2020.04.09.034942.Jia Y., Shen G., Zhang Y., Huang K-S., Ho H-Y., Hor W.S. et al. Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity. BioRxiv 2020. doi: 10.1101/2020.04.09.034942.Зайчук Т.А., Нечипуренко Ю.Д., Аджубей А.А., Оникиенко С.Б., Черешнев В.А., Зайнутдинов С.С. и др. Проблемы создания вакцин против бетакоронавирусов: антителозависимое усиление инфекции и вирус сендай как возможный вакцинный вектор. Молекулярная биология. — 2020. — Т. 54. — № 6. — С. 922–938.Zaichuk T.A., Nechipurenko Y.D., Adzhubei A.A., Onikienko S.B., Chereshnev V.A., Zainutdinov S.S. et al. The challenges of vaccine development against betacoronaviruses: antibody dependent enhancementand sendai virus as a possible vaccine vector. Journal of Molecular Biology 2020; 54 (6): 922–938. [in Russian]Zhang B., Liu S., Tan T., Huang W., Dong Y., Chen L. et al. Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection. Chest 2020; 158 (1): 9–13. doi: 10.1016/j.chest.2020.03.039.Zhang B., Liu S., Tan T., Huang W., Dong Y., Chen L. et al. Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection. Chest 2020; 158 (1): 9–13. doi: 10.1016/j.chest.2020.03.039.Duan K., Liu B., Li C., Zhang H., Yu T., Qu J. et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proceedings of the National Academy of Sciences of the United States of America 2020; 117 (17): 9490–9496. doi: 10.1073/pnas.2004168117.Duan K., Liu B., Li C., Zhang H., Yu T., Qu J. et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proceedings of the National Academy of Sciences of the United States of America 2020; 117 (17): 9490–9496. doi: 10.1073/pnas.2004168117.Jiang S., Hillyer C., Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Science & Society 2020; 41 (5): 355–359. doi: 10.1016/j.it.2020.03.007.Jiang S., Hillyer C., Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Science & Society 2020; 41 (5): 355–359. doi: 10.1016/j.it.2020.03.007.Wrapp D., de Vlieger D., Corbett K.S., Torres G.M., Wang N., van Breedam W. et al. Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies. Cell Press 2020; 181 (5): 1004–1015. doi: 10.1101/2020.03.26.010165.Wrapp D., de Vlieger D., Corbett K.S., Torres G.M., Wang N., van Breedam W. et al. Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies. Cell Press 2020; 181 (5): 1004–1015. doi: 10.1101/2020.03.26.010165.Горшкова Е.Н., Василенко Е.А., Тиллиб С.В., Астраханцева И.В. Однодоменные антитела и биоинженерные препараты на их основе: новые возможности для диагностики и терапии. Медицинская иммунология. — 2016. — Т. 18. — № 6. — С. 505–520. doi: 10.15789/1563-0625-2016-6-505-520.Gorshkova E.N., Vasilenko E.A., Tillib S.V., Astrakhantseva I.V. Single domain antibodies and bioengineering drugs on their basis: new opportunities for diagnostics and therapy. Meditsinskaya Immunologiya 2016; 18(6): 505–520. [in Russian] doi: 10.15789/1563-0625-2016-6-505-520.Krah S., Schröter C., Zielonka S., Empting M., Valldorf B., Kolmar H. Single-domain antibodies for biomedical applications. Immunopharmacol Immunotoxicol 2016; 38 (1): 21–28. doi: 10.3109/08923973.2015.1102934.Krah S., Schröter C., Zielonka S., Empting M., Valldorf B., Kolmar H. Single-domain antibodies for biomedical applications. Immunopharmacol Immunotoxicol 2016; 38 (1): 21–28. doi: 10.3109/08923973.2015.1102934.Koch C., Barrett D., Teachey T. Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome. Expert Rev Clin Immunol 2019; 15 (8): 813–822. doi: 10.1080/1744666X.2019.1629904.Koch C., Barrett D., Teachey T. Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome. Expert Rev Clin Immunol 2019; 15 (8): 813–822. doi: 10.1080/1744666X.2019.1629904.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. doi: 10.1016/j.autrev.2020.102537.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. doi: 10.1016/j.autrev.2020.102537.Liu B., Li M., Zhou Z., Guan X., Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmunity 2020; 111: 102452. doi: 10.1016/j.jaut.2020.102452.Liu B., Li M., Zhou Z., Guan X., Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmunity 2020; 111: 102452. doi: 10.1016/j.jaut.2020.102452.helpiks.org [Internet] Химерные белки [доступ от 04.10.2020]. Доступ по ссылке: https://helpiks.org/4-9030.htmlhelpiks.org [Internet] Химерные белки [доступ от 04.10.2020]. Доступ по ссылке: https://helpiks.org/4-9030.htmlMaude S.L., Frey N., Shaw P.A., Aplenc R., Barret D.M., Bunin N.J. et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. New England J Med 2014; 371 (16): 1507–1517. doi: 10.1056/NEJMoa1407222.Maude S.L., Frey N., Shaw P.A., Aplenc R., Barret D.M., Bunin N.J. et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. New England J Med 2014; 371 (16): 1507–1517. doi: 10.1056/NEJMoa1407222.Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19. ClinicalTrials.gov; 2020. Identifier: NCT04315298.Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19. ClinicalTrials.gov; 2020. Identifier: NCT04315298.Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients. ClinicalTrials.gov; 2020. Identifier: NCT04321993.Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients. ClinicalTrials.gov; 2020. Identifier: NCT04321993.A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: ChiCTR2000029765. ChiCTR; 2020.A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: ChiCTR2000029765. ChiCTR; 2020.Treatment of COVID-19 Patients With Anti-interleukin Drugs (COV-AID). ClinicalTrials.gov; 2020. Identifier: NCT04330638.Treatment of COVID-19 Patients With Anti-interleukin Drugs (COV-AID). ClinicalTrials.gov; 2020. Identifier: NCT04330638.Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection. ClinicalTrials.gov; 2020. Identifier: NCT04324021.Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection. ClinicalTrials.gov; 2020. Identifier: NCT04324021.A clinical study for the efficacy and safety of Adalimumab Injection in the treatment of patients with severe novel coronavirus pneumonia (COVID-19). Chin Clin Trial Registry: ChiCTR2000030089. ChiCTR; 2020.A clinical study for the efficacy and safety of Adalimumab Injection in the treatment of patients with severe novel coronavirus pneumonia (COVID-19). Chin Clin Trial Registry: ChiCTR2000030089. ChiCTR; 2020.Izana starts compassionate use study of potential Covid-19 drug. [Интернет]. — [доступ от 04.10.2020]. Доступ по ссылке: https://www.clinicaltrialsarena.com/news/izana-namilumab-covid-19-study/Izana starts compassionate use study of potential Covid-19 drug. [Интернет]. — [доступ от 04.10.2020]. Доступ по ссылке: https://www.clinicaltrialsarena.com/news/izana-namilumab-covid-19-study/Cytodyn.com [Internet]. Novant Health operates a fully integrated healthcare system throughout four states. [доступ от 04.10.2020]. Доступ по ссылке: https://www.cytodyn.com/newsroom/press-releases/detail/411/novant-health-initiatesphase-2-covid-19-trial-withCytodyn.com [Internet]. Novant Health operates a fully integrated healthcare system throughout four states. [доступ от 04.10.2020]. Доступ по ссылке: https://www.cytodyn.com/newsroom/press-releases/detail/411/novant-health-initiatesphase-2-covid-19-trial-withMehta Р., McAuley D.F., Brown M., Sanchez E., Tattesall R.S., Manson J.J. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033–1034. doi: 10.1016/S0140-6736(20)30628-0.Mehta Р., McAuley D.F., Brown M., Sanchez E., Tattesall R.S., Manson J.J. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033–1034. doi: 10.1016/S0140-6736(20)30628-0.Stebbing J., Phelan A., Griffin I., Tucker C., Oechsle O., Smith D. et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet 2020;.20 (4): 400–402. doi: 10.1016/S1473-3099(20)30132-8.Stebbing J., Phelan A., Griffin I., Tucker C., Oechsle O., Smith D. et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet 2020;.20 (4): 400–402. doi: 10.1016/S1473-3099(20)30132-8.Wu D., Yang X.O. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 2020; 53 (3): 368–370. doi: 10.1016/j.jmii.2020.03.005.Wu D., Yang X.O. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 2020; 53 (3): 368–370. doi: 10.1016/j.jmii.2020.03.005.Safety and Efficacy of Baricitinib for COVID-19. ClinicalTrials.gov; 2020. Identifier: NCT04340232.Safety and Efficacy of Baricitinib for COVID-19. ClinicalTrials.gov; 2020. Identifier: NCT04340232.Baricitinib in Symptomatic Patients Infected by COVID-19: an Openlabel, Pilot Study. (BARI-COVID). ClinicalTrials.gov; 2020. Identifier: NCT04320277.Baricitinib in Symptomatic Patients Infected by COVID-19: an Openlabel, Pilot Study. (BARI-COVID). ClinicalTrials.gov; 2020. Identifier: NCT04320277.Study of the Efficacy and Safety of Ruxolitinib to Treat COVID-19 Pneumonia. ClinicalTrials.gov; 2020. Identifier: NCT04331665.Study of the Efficacy and Safety of Ruxolitinib to Treat COVID-19 Pneumonia. ClinicalTrials.gov; 2020. Identifier: NCT04331665.Praveen D., Chowdary P.R., Aanandhi M.V. Baricitinib — a januase kinase inhibitor — not an ideal option for management of COVID 19. Intern J Antimicrob Agents 2020; 55 (5): 105967. doi: 10.1016/j.ijantimicag.2020.105967.Praveen D., Chowdary P.R., Aanandhi M.V. Baricitinib — a januase kinase inhibitor — not an ideal option for management of COVID 19. Intern J Antimicrob Agents 2020; 55 (5): 105967. doi: 10.1016/j.ijantimicag.2020.105967.Zhang R., Wang X., Ni L., Di X., Ma B., Niu S. et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sciences 2020; 250: 117583. doi: 10.1016/j.lfs.2020.117583.Zhang R., Wang X., Ni L., Di X., Ma B., Niu S. et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sciences 2020; 250: 117583. doi: 10.1016/j.lfs.2020.117583.Averyanov A., Koroleva I., Konoplyannikov M., Revkova V., Lesnyak V., Kalshin V. et al. First-inhuman high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline. STEM CELLS Translat Med 2020; 9 (1): 6–16. doi: 10.1002/sctm.19-0037.Averyanov A., Koroleva I., Konoplyannikov M., Revkova V., Lesnyak V., Kalshin V. et al. First-inhuman high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline. STEM CELLS Translat Med 2020; 9 (1): 6–16. doi: 10.1002/sctm.19-0037.Wilson J.G., Liu K.D., Zhuo H., Caballero L., McMillan M., Fang X. et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. The Lancet Respir Med 2015; 3 (1): 24–32. doi: 10.1016/S2213-2600(14)70291-7.Wilson J.G., Liu K.D., Zhuo H., Caballero L., McMillan M., Fang X. et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. The Lancet Respir Med 2015; 3 (1): 24–32. doi: 10.1016/S2213-2600(14)70291-7.globenewswire.com [Internet]. Sorrento to provide manufacturing support to celularity as CYNK-001 NK cell trial for COVID-19 begins enrolling patients. 2020. [доступ от 04.10.2020]. Доступ по ссылке: globenewswire.com/news-release/2020/04/02/2010998/0/en/Sorrento-toprovide-manufacturing-support-to-celularity-as-cynk-001-NK-celltrial-forcovid-19-begins-enrolling-patients.html.globenewswire.com [Internet]. Sorrento to provide manufacturing support to celularity as CYNK-001 NK cell trial for COVID-19 begins enrolling patients. 2020. [доступ от 04.10.2020]. Доступ по ссылке: globenewswire.com/news-release/2020/04/02/2010998/0/en/Sorrento-toprovide-manufacturing-support-to-celularity-as-cynk-001-NK-celltrial-forcovid-19-begins-enrolling-patients.html.A Phase I/II Study of Universal Off-the-shelf NKG2D-ACE2 CAR-NK Cells for Therapy of COVID-19. ClinicalTrials.gov; 2020. Identifier: NCT04324996.A Phase I/II Study of Universal Off-the-shelf NKG2D-ACE2 CAR-NK Cells for Therapy of COVID-19. ClinicalTrials.gov; 2020. Identifier: NCT04324996.Ahmed S.M., Luo L., Namani A., Wang X.J., Tang X. Nrf2 signaling pathway: pivotal roles in inflammation. Biochimica et Biophysica Acta 2017; 1863 (2): 585–597. doi: 10.1016/j.bbadis.2016.11.005.Ahmed S.M., Luo L., Namani A., Wang X.J., Tang X. Nrf2 signaling pathway: pivotal roles in inflammation. Biochimica et Biophysica Acta 2017; 1863 (2): 585–597. doi: 10.1016/j.bbadis.2016.11.005.Kobayashi E.H., Suzuki T., Funayama R., Nagashima T., Hayashi M., Sekine H. et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Communicat 2016; 7: 11624. doi: 10.1038/ncomms11624.Kobayashi E.H., Suzuki T., Funayama R., Nagashima T., Hayashi M., Sekine H. et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Communicat 2016; 7: 11624. doi: 10.1038/ncomms11624.

The authors declare that there are no conflicts of interest present.