Prospects for cytokine therapy in acute respiratory viral infections, including COVID-19

Abstract

Severe respiratory viral infections are accompanied by an unbalanced immune response due to suppression of endogenous interferon (IFN) synthesis, which leads to hyperproduction of proinflammatory cytokines. This results in inadequate inflammation in the lungs, accompanied by acute respiratory distress syndrome, respiratory failure, and dysfunction of other organs. Cytokine imbalance that underlies the immunopathogenesis of severe acute respiratory viral infections including COVID-19 offers the potential for two principal approaches to cytokine therapy, which are determined by the stage of the infectious process and the severity of clinical symptoms. Cytokine therapy with intranasal recombinant type I and III IFN represent a viable therapeutic strategy in prevention of virus infection or at early stages of the disease, particularly in endogenous IFN deficit at the onset. For example, during the COVID-19 pandemic, intranasal products based on recombinant IFNα2b demonstrated high antiviral activity and good tolerability, and are included in the national guidelines for control of coronavirus infection in Russia and other countries. This therapeutic approach aims at normalizing endogenous IFN expression, which may be inhibited by certain respiratory viruses, such as SARS-CoV-2. In cases of cytokine storm and severe respiratory infections, an anticytokine therapy may effectively inhibit the overproduction of proinflammatory cytokines. Both cytokine immunotherapies are based on using either synthetic analogs of endogenous cytokines or monoclonal antibodies that inhibit the cytokine up-regulation above physiological levels.

Keywords

intranasal interferon / proinflammatory cytokines / anticytokine therapy / COVID-19 immunopathogenesis

References

[1] Simbirtsev AS. Cytokine regulation disbalance: the basis for COVID-19 immunopathogenesis. Cytokines and Inflammation. 2023;20(2):12–23. doi: 10.17816/CI627301

[2] Симбирцев А.С. Дисбаланс цитокиновой регуляции — основа иммунопатогенеза COVID-19 // Цитокины и воспаление. 2023. Т. 20, № 2. С. 12–23. doi: 10.17816/CI627301

[3] Klimov NA, Simbirtsev AS. Role of inflammation in the pathogenesis of novel coronavirus infection. Cytokines and Inflammation. 2023;20(4):16–28. doi: 10.17816/CI630148

[4] Климов Н.А., Симбирцев А.С. Роль воспаления в патогенезе новой коронавирусной инфекции // Цитокины и воспаление. 2023. Т. 20, № 4. С. 16–28. doi: 10.17816/CI630148

[5] Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529–539. doi: 10.1007/s00281-017-0629-x

[6] Channappanavar R., Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology // Semin Immunopathol. 2017. Vol. 39, N 5. P. 529–539. doi: 10.1007/s00281-017-0629-x

[7] De Clercq E, Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev. 2016;29(3):695–747. doi: 10.1128/CMR.00102-15

[8] De Clercq E., Li G. Approved antiviral drugs over the past 50 years // Clin Microbiol Rev. 2016. Vol. 29, N 3. P. 695–747. doi: 10.1128/CMR.00102-15

[9] Kaufmann S, Dorhoi A, Hotchkiss R, Bartenschlager R. Host-directed therapies for bacterial and viral infections. Nat Rev Drug Disc. 2018;17(1):35–56. doi: 10.1038/nrd.2017.162

[10] Kaufmann S., Dorhoi A., Hotchkiss R., Bartenschlager R. Host-directed therapies for bacterial and viral infections // Nat Rev Drug Disc. 2018. Vol. 17, N 1. P. 35–56. doi: 10.1038/nrd.2017.162

[11] Hayden FG, Gwaltney JM Jr. Intranasal interferon-alpha 2 treatment of experimental rhinoviral colds. J Infect Dis. 1984;150(2):174–180. doi: 10.1093/infdis/150.2.174

[12] Hayden F.G., Gwaltney J.M. Jr. Intranasal interferon-alpha 2 treatment of experimental rhinoviral colds // J Infect Dis. 1984. Vol. 150, N 2. P. 174–180. doi: 10.1093/infdis/150.2.174

[13] Samo T, Greenberg S, Palmer J, et al. Intranasal applied recombinant leukocyte A interferon in normal volunteers. II. Determination of minimal effective and tolerable dose. J Infect Dis. 1984;150(2):181–188. doi: 10.1093/infdis/150.2.181

[14] Samo T., Greenberg S., Palmer J., et al. Intranasal applied recombinant leukocyte A interferon in normal volunteers. II. Determination of minimal effective and tolerable dose // J Infect Dis. 1984. Vol. 150, N 2. P. 181–188. doi: 10.1093/infdis/150.2.181

[15] Monto AS, Shope TC, Schwartz SA, Albrecht JK. Intranasal interferon-alpha 2b for seasonal prophylaxis of respiratory infection. J Infect Dis. 1986;154(1):128–133. doi: 10.1093/infdis/154.1.128

[16] Monto A.S., Shope T.C., Schwartz S.A., Albrecht J.K. Intranasal interferon-alpha 2b for seasonal prophylaxis of respiratory infection // J Infect Dis 1986. Vol. 154, N 1. P. 128–1133. doi: 10.1093/infdis/154.1.128

[17] Hayden FG, Kaiser DL, Albrecht JK. Intranasal recombinant alfa-2b interferon treatment of naturally occurring common colds. Antimicrob Agents Chemother. 1988;32(2):224–230. doi: 10.1128/AAC.32.2.224

[18] Hayden F.G., Kaiser D.L., Albrecht J.K. Intranasal recombinant alfa-2b interferon treatment of naturally occurring common colds // Antimicrob Agents Chemother. 1988. Vol. 32, N 2. P. 224–230. doi: 10.1128/AAC.32.2.224

[19] Monto AS, Albrecht JK, Schwartz SA. Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon. Antimicrob Agents Chemother. 1988;32(1):47–50. doi: 10.1128/AAC.32.1.47

[20] Monto A.S., Albrecht J.K., Schwartz S.A. Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon // Antimicrob Agents Chemother. 1988. Vol. 32, N 1. P. 47–50. doi: 10.1128/AAC.32.1.47

[21] Higgins PG, Barrow GI, Tyrrell DA, et al. The efficacy of intranasal interferon alpha-2a in respiratory syncytial virus infection in volunteers. Antiviral Res. 1990;14(1):3–10. doi: 10.1016/0166-3542(90)90061-b

[22] Higgins P.G., Barrow G.I., Tyrrell D.A., et al. The efficacy of intranasal interferon alpha-2a in respiratory syncytial virus infection in volunteers // Antiviral Res 1990. Vol. 14, N 1. P. 3–10. doi: 10.1016/0166-3542(90)90061-b

[23] Hayden FG, Mills SE, Johns ME. Human tolerance and histopathologic effects of long-term administration of intranasal interferon-alpha 2. J Infect Dis. 1983;148(5):914–921. doi: 10.1093/infdis/148.5.914

[24] Hayden F.G., Mills S.E., Johns M.E. Human tolerance and histopathologic effects of long-term administration of intranasal interferon-alpha 2 // J Infect Dis. 1983. Vol. 148, N 5. P. 914–921. doi: 10.1093/infdis/148.5.914

[25] Herzog C, Berger R, Fernex M, et al. Intranasal interferon (rIFN-alpha A, Ro 22-8181) for contact prophylaxis against common cold: a randomized, double-blind and placebo-controlled field study. Antiviral Res. 1986;6(3):171–176. doi: 10.1016/0166-3542(86)90011-2

[26] Herzog C., Berger R., Fernex M., et al. Intranasal interferon (rIFN-alpha A, Ro 22-8181) for contact prophylaxis against common cold: a randomized, double-blind and placebo-controlled field study // Antiviral Res. 1986. Vol. 6, N 3. P. 171–176. doi: 10.1016/0166-3542(86)90011-2

[27] Tyrrell DA. The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit. J Antimicrob Chemother. 1986;18 Suppl. B:153–156. doi: 10.1093/jac/18.supplement_b.153

[28] Tyrrell D.A. The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit // J Antimicrob Chemother. 1986. Vol. 18, Suppl. B. P. 153–156. doi: 10.1093/jac/18.supplement_b.153

[29] Feklisova LV, Shebekova VM, Tselipanova EE, et al. Grippferon in children with acute respiratory viral infection. Vrach. 2001;42(3):40–41. (In Russ.)

[30] Феклисова Л.В., Шебекова В.М., Целипанова Е.Е., и др. Гриппферон у детей, больных ОРВИ // Врач. 2001. Т. 42, № 3. С. 40–41.

[31] Gaponyuk PYa, Kuzminskaya LM. Clinical and epidemiological effectiveness of Grippferon, nasal drops, in acute respiratory viral infection and influenza. Sanitarno-ghighienichesky vestnik. 2002;(1):26–27. (In Russ.)

[32] Гапонюк П.Я., Кузьминская Л.М. Клиническая и эпидемиологическая эффективность препарата Гриппферон, капли в нос при ОРВИ и гриппе // Санитарно-гигиенический вестник. 2002. № 1. С. 26–27.

[33] Abdulkerimov HT, Simbirtsev AS, Savlevich EL, Brodovskaya OB. Results of the recombinant interferon alpha aerosol form application for with acute respiratory viral infection patients therapy. Rossiiskaya otorinolaringologiya. 2009;(2(39)):20–32. (In Russ.) EDN: MGSYTZ

[34] Абдулкеримов Х.Т., Симбирцев А.С., Савлевич Е.Л., Бродовская О.Б. Результаты применения аэрозольной формы рекомбинантного интерферона альфа 2 человека в лечении больных ОРВИ // Российская оториноларингология. 2009. № 2 (39). С. 28–32. EDN: MGSYTZ

[35] Savlevich EL, Brodovskaya OB, Remizova II, et al. Clinical and immunological aspects of the application of the new aerosol form of recombinant interferon α2b in the treatment of patients with acute nasopharingitis. Cytokines and inflammation. 2010;9(1):49–56. EDN: OGAGEJ

[36] Савлевич Е.Л., Бродовская О.Б., Ремизова И.И., и др. Клинико-иммунологическая эффективность применения новой аэрозольной формы рекомбинантного интерферона-α2b в лечении больных с острыми назофарингитами // Цитокины и воспаление. 2010. Т. 9, № 1. С. 49–56. EDN: OGAGEJ

[37] Voloschuk LV, Golovacheva EG, Mushkatina AL, et al. Effect of complex therapy with cytokines in flu and respiratory infections for adults. Journal Infectology. 2012;4(4):52–58. doi: 10.22625/2072-6732-2012-4-4-52-58

[38] Волощук Л.В., Головачева Е.Г., Мушкатина А.Л., и др. Цитокинсодержащие препараты в комплексной терапии гриппа и гриппоподобных заболеваний у взрослых // Журнал инфектологии. 2012. Т. 4, № 4. С. 52–58. doi: 10.22625/2072-6732-2012-4-4-52-58

[39] Gao L, Yu S, Chen Q, et al. A randomized controlled trial of low-dose recombinant human interferons alpha-2b nasal spray to prevent acute viral respiratory infections in military recruits. Vaccine. 2010;28(28):4445–4451. doi: 10.1016/j.vaccine.2010.03.062

[40] Gao L., Yu S., Chen Q., et al. A randomized controlled trial of low-dose recombinant human interferons alpha-2b nasal spray to prevent acute viral respiratory infections in military recruits // Vaccine. 2010. Vol. 28, N 28. P. 4445–4451. doi: 10.1016/j.vaccine.2010.03.062

[41] Baranova IP, Svistunova NV. Comparative study of the effectiveness of antiviral drugs in complex treatment of influenza. Infektsionnye bolezni. 2014;12(2):46–53. EDN: SLJOGB

[42] Баранова И.П., Свистунова Н.В. Сравнительное исследование эффективности антивирусных препаратов в комплексном лечении гриппа // Инфекционные болезни. 2014. Т. 12, № 2. С. 46–53. EDN: SLJOGB

[43] Osidak LV, Yanina MA, Zarubaeb VV, et al. Prevention of adenovirus infection with recombinant interferon a2b medication in preschool institutions. Children Infections. 2016;15(2):9–14. doi: 10.22627/2072-8107-2016-15-2-9-14

[44] Осидак Л.В., Янина М.А., Зарубаев В.В., и др. Профилактика аденовирусной инфекции в детских дошкольных учреждениях с помощью препарата рекомбинантного интерферона а2b // Детские инфекции. 2016. Т. 15, № 2. С. 9–14. doi: 10.22627/2072-8107-2016-15-2-9-14

[45] Krasnov VV. The efficacy of recombinant interferon-alpha in the treatment and prevention of ARVI. Voprosy practicheskoy pediatrii. 2016;11(4):44–52. doi: 10.20953/1817-7646-2016-4-44-52

[46] Краснов В.В. Эффективность рекомбинантного интерферона-альфа в лечении и профилактике ОРВИ // Вопросы практической педиатрии. 2016. Т. 11, № 4. С. 44–52. doi: 10.20953/1817-7646-2016-4-44-52

[47] Burtseva EI, Mukasheva EA, Rosatkevich AG. Main directions of effective influenza prevention in modern conditions. Epidemiology and Vaccinal Prevention. 2017;16(5):80–86. (In Russ.) doi: 10.31631/2073-3046-2017-16-5-80-86

[48] Бурцева Е.И., Мукашева Е.А., Росаткевич А.Г. Основные направления эффективной профилактики гриппа в современных условиях // Эпидемиология и Вакцинопрофилактика. 2017. Т. 16, № 5 (96). С. 80–86. doi: 10.31631/2073-3046-2017-16-5-80-86

[49] Banerjee A, Blanco M, Bruce E, et al. SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses. Cell. 2020;183(5):1325–1339.e21. doi: 10.1016/j.cell.2020.10.004

[50] Banerjee A., Blanco M., Bruce E., et al. SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses // Cell. 2020. Vol. 183, N 5. P. 1325–1339.e21. doi: 10.1016/j.cell.2020.10.004

[51] Steiner S, Kratzel A, Barut GT, et al. SARS-CoV-2 biology and host interactions. Nat Rev Microbiol. 2024;22(4):206–225. doi: 10.1038/s41579-023-01003-z

[52] Steiner S., Kratzel A., Barut G.T., et al. SARS-CoV-2 biology and host interactions // Nat Rev Microbiol. 2024. Vol. 22, N 4. P. 206–225. doi: 10.1038/s41579-023-01003-z

[53] Falzarano D, de Witt E, Rasmussen A, et al. Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med. 2013;19(10):1313–1317. doi: 10.1038/nm.3362

[54] Falzarano D., de Witt E., Rasmussen A., et al. Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques // Nat Med. 2013. Vol. 19, N 10. P. 1313–1317. doi: 10.1038/nm.3362

[55] Deryabin PG, Zarubaev VV. Regarding the Coronavirus infection and prospects for prevention and treatment by recombinant human interferon alpha-2b medications. Infectious Diseases. 2014;12(3):32–34. (In Russ.) EDN: TGFXHT

[56] Дерябин П.Г., Зарубаев В.В. К вопросу о коронавирусной инфекции и перспективах профилактики и лечения препаратами интерферона альфа-2b человеческого рекомбинантного // Инфекционные болезни. 2014. Т. 12, № 3. С. 32–34. EDN: TGFXHT

[57] Tyrrell D. The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit. J Antimicrob Chemother. 1986;18 Suppl. B:153–156. doi: 10.1093/jac/18.supplement_b.153

[58] Tyrrell D. The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit // J Antimicrob Chemother. 1986. Vol. 18, Suppl. B. P. 153–156. doi: 10.1093/jac/18.supplement_b.153

[59] Loginova SY, Shсhukina VN, Savenko SV, Borisevich SV. In vitro activity of human recombinant alpha-2b interferon against SARS-CoV-2 virus. Problems of Virology. 2021;66(2):123–128. doi: 10.36233/0507-4088-13

[60] Логинова С.Я., Щукина В.Н., Савенко С.В., Борисевич С.В. Активность человеческого рекомбинантного интерферона альфа-2b in vitro в отношении вируса SARS-CoV-2 // Вопросы вирусологии. 2021. Vol. 66, N 2. P. 123–128. doi: 10.36233/0507-4088-13

[61] Mesev EV, LeDesma RA, Ploss A. Decoding type I and III interferon signalling during viral infection. Nat Microbiol. 2019;4(6):914–924. doi: 10.1038/s41564-019-0421-x

[62] Mesev E.V., LeDesma R.A., Ploss A. Decoding type I and III interferon signalling during viral infection // Nat Microbiol. 2019. Vol. 4, N 6. P. 914–924. doi: 10.1038/s41564-019-0421-x

[63] Wittling MC, Cahalan SR, Levenson EA, Rabin RL. Shared and unique features of human interferon-beta and interferon-alpha subtypes. Front Immunol. 2021;11:605673. doi: 10.3389/fimmu.2020.605673

[64] Wittling M.C., Cahalan S.R., Levenson E.A., Rabin R.L. Shared and unique features of human interferon-beta and interferon-alpha subtypes // Front Immunol. 2021. Vol. 11. P. 605673. doi: 10.3389/fimmu.2020.605673

[65] Schuhenn J, Meister TL, Todt D, et al. Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection. Proc Natl Acad Sci USA. 2022;119(8):e2111600119. doi: 10.1073/pnas.2111600119

[66] Schuhenn J., Meister T.L., Todt D., et al. Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection // Proc Natl Acad Sci USA. 2022. Vol. 119, N 8. P. e2111600119. doi: 10.1073/pnas.2111600119

[67] Omrani A, Saad M, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14(11):1090–1095. doi: 10.1016/S1473-3099(14)70920-X

[68] Omrani A., Saad M., Baig K., et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study // Lancet Infect Dis. 2014. Vol. 14, N 11. P. 1090–1095. doi: 10.1016/S1473-3099(14)70920-X

[69] Zumla A, Chan J, Azhar E, et al. Coronaviruses — drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327–347. doi: 10.1038/nrd.2015.37

[70] Zumla A., Chan J., Azhar E., et al. Coronaviruses — drug discovery and therapeutic options // Nat Rev Drug Discov. 2016. Vol. 15, N 5. P. 327–347. doi: 10.1038/nrd.2015.37

[71] Park A, Iwasaki A. Type I and Type III Interferons — Induction, Signaling, Evasion, and Application to Combat COVID-19. Cell Host Microbe. 2020;27(6):870–878. doi: 10.1016/j.chom.2020.05.008

[72] Park A., Iwasaki A. Type I and Type III Interferons — Induction, Signaling, Evasion, and Application to Combat COVID-19 // Cell Host Microbe. 2020. Vol. 27, N 6. P. 870–878. doi: 10.1016/j.chom.2020.05.008

[73] Zhou Q, Chen V, Shannon C, et al. Interferon-α2b Treatment for COVID-19. Front Immunol. 2020;11:1061. doi: 10.3389/fimmu.2020.01061 Erratum in: Front Immunol. 2020;11:615275. doi: 10.3389/fimmu.2020.615275

[74] Zhou Q., Chen V., Shannon C., et al. Interferon-α2b Treatment for COVID-19 // Front Immunol. 2020. Vol. 11. P. 1061. doi: 10.3389/fimmu.2020.01061 Erratum in: Front Immunol. 2020. Vol. 11. P. 615275. doi: 10.3389/fimmu.2020.615275

[75] Monk PD, Marsden RJ, Tear VJ, et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(2):196–206. doi: 10.1016/S2213-2600(20)30511-7

[76] Monk P.D., Marsden R.J., Tear V.J., et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial // Lancet Respir Med. 2021. Vol. 9, N 2. P. 196–206. doi: 10.1016/S2213-2600(20)30511-7

[77] Rahmani H, Davoudi-Monfared E, Nourian A, et al. Interferon β-1b in treatment of severe COVID-19: A randomized clinical trial. Int Immunopharmacol. 2020;88:106903. doi: 10.1016/j.intimp.2020.106903

[78] Rahmani H., Davoudi-Monfared E., Nourian A., et al. Interferon β-1b in treatment of severe COVID-19: A randomized clinical trial // Int Immunopharmacol. 2020. Vol. 88. P. 106903. doi: 10.1016/j.intimp.2020.106903

[79] Reis G, Moreira Silva EAS, Medeiros Silva DC, et al. Early treatment with pegylated interferon lambda for Covid-19. N Engl J Med. 2023;388(6):518–528. doi: 10.1056/NEJMoa2209760

[80] Reis G., Moreira Silva E.A.S., Medeiros Silva D.C., et al. Early treatment with pegylated interferon lambda for Covid-19 // N Engl J Med. 2023. Vol. 388, N 6. P. 518–528. doi: 10.1056/NEJMoa2209760

[81] Meng Z, Wang T, Chen L, et al. The Effect of Recombinant Human Interferon Alpha Nasal Drops to Prevent COVID-19 Pneumonia for Medical Staff in an Epidemic Area. Curr Top Med Chem. 2021;21(10):920–927. doi: 10.2174/1568026621666210429083050

[82] Meng Z., Wang T., Chen L., et al. The Effect of Recombinant Human Interferon Alpha Nasal Drops to Prevent COVID-19 Pneumonia for Medical Staff in an Epidemic Area // Curr Top Med Chem. 2021. Vol. 21, N 10. P. 920–927. doi: 10.2174/1568026621666210429083050

[83] Feldblyum IV, Devyatkov MYu, Gendler AA, et al. The efficacy of intranasal recombinant interferon alpha-2b for emergency prevention of COVID-19 in healthcare workers. Infectious Diseases. 2021;19(1):26–32. doi: 10.20953/1729-9225-2021-1-26-32

[84] Фельдблюм И.В., Девятков М.Ю., Гендлер А.А., и др. Эффективность рекомбинантного интерферона альфа при интраназальном применении для экстренной профилактики COVID-19 у медицинских работников // Инфекционные болезни. 2021. Т. 19, № 1. С. 26–32. doi: 10.20953/1729-9225-2021-1-26-32

[85] Khlynina YuO, Arova AA, Nevinsky AB. The use of interferon alpha-2b for prevention of novel coronavirus infection in healthcare workers. Infectious Diseases. 2021;19(2):65–69. doi: 10.20953/1729-9225-2021-2-65-69

[86] Хлынина Ю.О., Арова А.А., Невинский А.Б. Применение интерферона альфа-2b для профилактики новой коронавирусной инфекции у медицинских работников // Инфекционные болезни. 2021. Т.19, № 2. С. 65–69. doi: 10.20953/1729-9225-2021-2-65-69

[87] Nesterova IV, Gorodin VN, Chudilova GA, et al. Effects of recombinant IFN-a2b on the phenotype of neutrophil granulocyte subpopulations in patients with COVID-19. Infectious Diseases. 2022;20(1):43–51. doi: 10.20953/1729-9225-2022-1-43-51

[88] Нестерова И.В., Городин В.Н., Чудилова Г.А., и др. Эффекты влияния рекомбинантного интерферона a-2b на фенотип субпопуляций нейтрофильных гранулоцитов пациентов с COVID-19 // Инфекционные болезни. 2022. Т. 20, № 1. С. 43–51. doi: 10.20953/1729-9225-2022-1-43-51

[89] Afanasyeva OI, Golovacheva EG, Osidak LV, et al. Cytokine status indicators in children with acute respiratory viral infections after treatment with intranasal interferon-based medicine. Children Infections. 2021;20(4):6–12. doi: 10.22627/2072-8107-2021-20-4-6-12

[90] Афанасьева О.И., Головачева Е.Г., Осидак Л.В., и др. Показатели цитокинового статуса у детей с ОРВИ на фоне терапии интраназальными препаратами интерферона // Детские инфекции. 2021. Т. 20, № 4. С. 6–12. doi: 10.22627/2072-8107-2021-20-4-6-12

[91] Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20):10970–10975. doi: 10.1073/pnas.2005615117

[92] Xu X., Han M., Li T., et al. Effective treatment of severe COVID-19 patients with tocilizumab // Proc Natl Acad Sci U S A. 2020. Vol. 117, N 20. P. 10970–10975. doi: 10.1073/pnas.2005615117

[93] Michot JM, Albiges L, Chaput N, et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol. 2020;31(7):961–964. doi: 10.1016/j.annonc.2020.03.300

[94] Michot J.-M., Albiges L., Chaput N., et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report // Ann Oncol. 2020. Vol. 31, N 7. P. 961–964. doi: 10.1016/j.annonc.2020.03.300

[95] Nasonov EL. Coronavirus disease-2019 (COVID-19): value of IL-6 inhibitors. Pulmonologiya. 2020;30(5):629–644. doi: 10.18093/0869-0189-2020-30-5-629-644

[96] Насонов Е.Л. Коронавирусная болезнь-2019 (COVID-19): значение ингибиторов IL-6 // Пульмонология. 2020. Т. 30, № 5. С. 629–644. doi: 10.18093/0869-0189-2020-30-5-629-644

[97] Writing Committee for the REMAP-CAP Investigators; Higgins AM, Berry LR, Lorenzi E, et al. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial. JAMA. 2023;329(1):39–51. doi: 10.1001/jama.2022.23257

[98] Writing Committee for the REMAP-CAP Investigators; Higgins A.M., Berry L.R., Lorenzi E., et al. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial // JAMA. 2023. Vol. 329, N 1. P. 39–51. doi: 10.1001/jama.2022.23257

[99] RECOVERY Collaborative Group. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. Lancet. 2022;400(10349):359–368. doi: 10.1016/S0140-6736(22)01109-6 Erratum in: Lancet. 2022;400(10358):1102. doi: 10.1016/S0140-6736(22)01866-9

[100] RECOVERY Collaborative Group. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis // Lancet. 2022. Vol. 400, N 10349. P. 359–368. doi: 10.1016/S0140-6736(22)01109-6 Erratum in: Lancet. 2022. Vol. 400, N 10358. P. 1102. doi: 10.1016/S0140-6736(22)01866-9

[101] Guimarães PO, Quirk D, Furtado RH, et al. Tofacitinib in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;385(5):406–415. doi: 10.1056/NEJMoa2101643

[102] Guimarães P.O., Quirk D., Furtado R.H., et al. Tofacitinib in patients hospitalized with Covid-19 pneumonia // N Engl J Med. 2021. Vol. 385, N 5. P. 406–415. doi: 10.1056/NEJMoa2101643

[103] DeFrancesco L. COVID-19 antibodies on trial. Nat Biotechnol. 2020;38:1242–1252. doi: 10.1038/s41587-020-0732-8

[104] DeFrancesco L. COVID-19 antibodies on trial // Nat Biotechnol. 2020. Vol. 38. P. 1242–1252. doi: 10.1038/s41587-020-0732-8

[105] Taylor PC, Adams AC, Hufford MM, et al. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol. 2021;21(6):382–393. doi: 10.1038/s41577-021-00542-x

[106] Taylor P.C., Adams A.C., Hufford M.M., et al. Neutralizing monoclonal antibodies for treatment of COVID-19 // Nat Rev Immunol. 2021. Vol. 21, N 6. P. 382–393. doi: 10.1038/s41577-021-00542-x

[107] Biancolella M, Colona VL, Luzzatto L, et al. COVID-19 annual update: a narrative review. Hum Genomics. 2023;17(1):68. doi: 10.1186/s40246-023-00515-2

[108] Biancolella M., Colona V.L., Luzzatto L., et al. COVID-19 annual update: a narrative review // Hum Genomics. 2023. Vol. 17, N 1. P. 68. doi: 10.1186/s40246-023-00515-2

RIGHTS & PERMISSIONS

Simbirtsev A.S.