The problem of the use of interferons in the novel coronavirus disease COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus)

Cover Page

Cite item


By the end of 2021, about 200 studies on the effect of interferons (IFNs) on the incidence and course of the new coronavirus infection COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) have been reported worldwide, with the number of such studies steadily increasing. This review discusses the main issues of the use of IFN drugs in this disease. The literature search was carried out in the PubMed, Scopus, Cochrane Library, Web of Science, RSCI databases, as well as in the Google Scholar preprint database using the available search queries «MeSH for coronavirus», «SARS-CoV-2», «IFN drugs», and «COVID-19». Interferon therapy is indicated for early administration (within the first 5 days of patient admission) in cases of mild to moderate COVID-19 to take advantage of the narrow therapeutic window of IFNs action. Control and suppression of viral replication requires therapy with IFNs and other effective antiviral agents that inhibit the reproduction of SARS-CoV-2 and induce several interferon-stimulated genes (ISG). Type I IFNs (IFN-I) exhibit potent pro-inflammatory properties and activate a wide variety of different cell types that respond to IFNs stimulation and pathogen entry. IFN-III confer local mucosal antiviral immunity without inducing the strong systemic pro-inflammatory responses associated with IFN-I. The use of IFNs drugs in the therapy of new coronavirus infection requires a cautious and differentiated approach, because in severe cases they can aggravate viral pathogenesis by causing excessive intensity of inflammatory reactions. The unique biological properties of substances of this class allow us to consider them as therapeutic agents with significant potential for use in patients with COVID-19.

About the authors

F. I. Ershov

FSBI «National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya» of the Ministry of Health of Russia

Author for correspondence.
ORCID iD: 0000-0002-4780-7560

Felix I. Ershov, - Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Chief Researcher 

Moscow, 123098

eLIBRARY SPIN 3076-4864


Russian Federation

A. N. Narovlyansky

FSBI «National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya» of the Ministry of Health of Russia


Alexander N. Narovlyansky, - Doctor of Biological Sciences, Professor, Chief Researcher, Head of Laboratory

Moscow, 123098

eLIBRARY SPIN 9015-5536

Russian Federation


  1. Временные методические рекомендации. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 14 (27.12.2021). Available at: (accessed January 28, 2022).
  2. Ершов Ф.И., Наровлянский А.Н. Интерфероны и индукторы интерферонов. В кн.: Хаитова Р.М., Атауллаханова Р.И., Шульженко А.Е., ред. Иммунотерапия: руководство для врачей. М.: ГЭОТАР-Медиа; 2018: 123–47.
  3. Schreiber G. The role of type I interferons in the pathogenesis and treatment of COVID-19. Front. Immunol. 2020; 11: 595739.
  4. is a database of privately and publicly funded clinical studies conducted around the world. Available at: (accessed January 27, 2022).
  5. Walz L., Cohen A.J., Rebaza A.P., Vanchieri J., Slade M.D., Dela Cruz C.S., et al. JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis. BMC Infect. Dis. 2021; 21(1): 47.
  6. Falzarano D., de Witt E., Rasmussen A., Feldmann F., Okumura A., Scott D.P., et al. Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 2013; 19(10): 1313–7.
  7. Cinatl J., Morgenstern B., Bauer G., Chandra P., Rabenau H., Doerr H.W. Treatment of SARS with human interferons. Lancet. 2003; 362(9380): 293–4.
  8. Sainz B., Mossel E.C., Peters C.J., Garry R.F. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARSCoV). Virology. 2004; 329(1): 11–7.
  9. Brzoska J., von Eick H., Hündgen M. Interferons in the therapy of severe coronavirus infections: a critical analysis and recollection of a forgotten therapeutic regimen with interferon beta. Drug Res. (Stuttg.). 2020; 70(7): 291–7.
  10. Hung I.F., Lung K.-C., Tso E.Y., Liu R., Chung T.W., Chu M.Y., et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; 395(10238): 1695–704.
  11. Lee A.J., Ashkar A.A. The dual nature of type I and type II interferons. Front. Immunol. 2018; 9: 2061.
  12. Mosaddeghi P., Shahabinezhad F., Dehghani Z., Farahmandnejad M., et al. Therapeutic Approaches for COVID-19 Based on the Interferon-mediated Immune Responses. Curr. Signal Transduct. Ther. 2021; 16(3): 269–79.
  13. Lokugamage K.G., Hage A., de Vries M., Valero-Jimenez A.M., Schindewolf C., Dittmann M., et al. Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. J. Virol. 2020; 94(23): e01410-20.
  14. Zhou Q., Chen V., Shannon C.P., Wei X.S., Xiang X., Wang X., et al. Interferon-a2b Treatment for COVID-19. Front. Immunol. 2020; 11: 1061.
  15. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229): 1054–62.
  16. Wang N., Zhan Y., Zhu L., Hou Z., Liu F., Song P., et al. Retrospective multicenter cohort study shows early interferon therapy is associated with favorable clinical responses in COVID-19 patients. Cell Host Microbe. 2020; 28(3): 455–64.e2.
  17. Mantlo E., Bukreyeva N., Maruyama J., Paessler S., Huang C. Antiviral activities of type I interferons to SARS-CoV-2 infection. Antiviral Res. 2020; 179: 104811.
  18. Pandit A., Bhalani N., Bhushan B.L.S., Koradia P., Gargiya S., Bhomia V., et al. Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study. Int. J. Infect. Dis. 2021; 105: 516–21.
  19. Понежева Ж.Б., Гришаева А.А., Маннанова И.В., Купченко А.Н., Яцышина С.Б., Краснова С.В., и др. Профилактическая эффективность рекомбинантного интерферона α-2b в условиях пандемии COVID-19. Лечащий врач. 2020; (12): 56–60.
  20. Omrani A.S., Saad M.M., Baig K., Bahloul A., Abdul-Matin M., Alaidaroos A.Y., 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): 1090–5.
  21. Feldstein L.R. Rose E.B., Horwitz S.M., Collins J.P., Newhams M.M., Son M.B.F., et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N. Engl. J. Med. 2020; 383(4): 334– 46.
  22. Weisberg S.P., Connors T.J., Zhu Y., Baldwin M.R., Lin W.H., Wontakal S., et al. Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nat. Immunol. 2021; 22(1): 25–31.
  23. Borrelli M., Corcione A., Castellano F., Fiori Nastro F., Santamaria F. Coronavirus disease 2019 in children. Front. Pediatr. 2021; 9: 668484.
  24. Методические рекомендации «Особенности клинических проявлений и лечения заболевания, вызванного новой коронавирусной инфекцией (COVID-19) у детей». Версия 1 (24.04.2020) Минздрав РФ. Available at: (accessed January 24, 2022).
  25. Мазанкова Л.Н., Горбунов С.Г., Самитова Э.Р. Значение интерферонотерапии при COVID-19 у детей. Детские инфекции. 2021; 20(1): 34–8.
  26. Loske, J., Röhmel, J., Lukassen S., Stricker S., Magalhães V.G., Liebig J., et al. Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children. Nat. Biotechnol. 2021.
  27. Xu Y., Li X., Zhu B., Liang H., Fang C., Gong Y., et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat. Med. 2020; 26(4): 502–5.
  28. Сафина А.И., Шарипова О.В., Лутфуллин И.Я., Наумова О.С., Даминова М.А. Современные возможности интерферонов в лечении детей с COVID-19. Медицинский совет. 2021; (1): 59–65.
  29. Новая коронавирусная инфекция COVID-19 у детей. Эффективная фармакотерапия. Педиатрия. 2020; 16(34): 32–34.
  30. Robinson J. Everything you need to know about the COVID-19 therapy trials. Pharm. J. 2021. Available at: (accessed January 20, 2022).
  31. Monk P.D., Marsden R.J., Tear V.J., Brookes J., Batten T.N., Mankowski M., 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.
  32. Kim Y.M., Shin E.C. Type I and III interferon responses in SARSCoV-2 infection. Exp. Mol. Med. 2021; 53(5): 750–60.
  33. Garcia-del-Barco D., Risco-Acevedo D., Berlanga-Acosta J., Martos-Benítez F.D., Guillén-Nieto G. Revisiting pleiotropic effects of type I interferons: rationale for its prophylactic and therapeutic use against SARS-CoV-2. Front. Immunol. 2021; 12: 655528.
  34. Juul S., Nielsen E.E., Feinberg J., Siddiqui F., Jørgensen C.K., Barot E., et al. Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project). PLoS One. 2021; 16(3): e0248132.
  35. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. WHO Solidarity Trial Consortium*. N. Engl. J. Med. 2021; 384(6): 497–511.
  36. Davoudi-Monfared E., Rahmani H., Khalili H., Hajiabdolbaghi M., Salehi M., Abbasian L., et al. 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): e0106120.
  37. Hadjadj J., Yatim N., Barnabei L., Corneau A., Boussier J., Smith N., et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369(6504): 718–24.
  38. Lucas C., Wong P., Klein J., Castro T.B.R., Silva J., Sundaram M., et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020; 584(7821): 463–9.
  39. Lee J.S., Park S., Jeong H.W., Ahn J.Y., Choi S.J., Lee H., et al. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci. Immunol. 2020; 5(49): eabd1554.
  40. Dorgham K., Neumann A.U., Decavele M., Luyt C.E., Yssel H., Gorochov G. Considering personalized interferon beta therapy for COVID-19. Antimicrob. Agents Chemother. 2021; 65(4): e0006521.
  41. Bastard P., Rosen L.B., Zhang Q., Michailidis E., Hoffmann H.H., Zhang Y., et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020; 370(6515): eabd4585.
  42. Sosa J.P., Ferreira Caceres M.M., Ross Comptis J., Quiros J., Príncipe-Meneses F.S., Riva-Moscoso A., et al. Effects of Interferon Beta in COVID-19 adult patients: Systematic Review. Infect. Chemother. 2021; 53(2): 247–60.
  43. Interferon beta-1b: Drug information. Available at: (accessed January 20, 2022).
  44. IMMUKIN 2 × 106 IU (0.1 mg) solution for injection. Available at: (accessed January 24, 2022).
  45. ACTIMMUNE® (Interferon gamma-1b). Available at: (accessed January 24, 2022).
  46. Киселёв О.И., Ершов Ф.И., Деева Э.Г. Интерферон-гамма: новый цитокин в клинической практике. Ингарон®. М.: Димитрейд График Групп; 2007.
  47. Bello-Rivero I., Garcia-Vega Y., Duncan-Roberts Y., Vazquez-Blomquistc D., Santana-Milian H., Besada-Perez V., et al. HeberFERON, a new formulation of IFNs with improved pharmacodynamics: Perspective for cancer treatment. Semin. Oncol. 2018; 45(1-2): 27–33.
  48. Мясников А.Л., Бернс С.А., Талызин П.А., Ершов Ф.И. Интерферон гамма в терапии пациентов с COVID-19 среднетяжёлого течения. Вопросы вирусологии. 2021; 66(1): 47–54.
  49. Белевский А.С., Бернс С.А., Ларцева О.А., Мясников А.Л., Надарая В.М., Талызин П.А. Эффективность и безопасность гамма-интерферона при лечении внебольничной пневмонии: результаты открытого рандомизированного исследования IN/100000-317. Медицина. 2019; 7(4): 110–25.
  50. Idelsis E.M.I., Pérez-Escribano J., Duncan-Roberts Y., Dania V.B.D., Bequet-Romero M., Baez-Rodríguez L., et al. Effect of combination of interferon alpha-2b and interferon-gamma or interferon alpha2b alone for elimination of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. medRxiv. 2020. Preprint.
  51. Karki R., Sharma B.R., Tuladhar S., Williams E.P., Zalduondo L., Samir P., et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021; 184(1): 149-168. e17.
  52. Broggi A., Ghosh S, Sposito B., Spreafico R., Balzarini F., Lo Cascio A., et al. Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science. 2020; 369(6504): 706–12.
  53. Prokunina-Olsson L., Alphonse N., Dickenson R.E., Durbin J.E., Glenn J.S., Hartmann R., et al. COVID-19 and emerging viral infections: the case for interferon lambda. J. Exp. Med. 2020; 217(5): e20200653.
  54. Rivera A. Interferon Lambda’s new role as regulator of neutrophil function. J. Interferon. Cytokine Res. 2019; 39(10): 609–17.
  55. Dinnon K.H. 3rd, Leist S.R., Schäfer A., Edwards C.E., Martinez D.R., Montgomery S.A., et al. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature. 2020; 586(7830): 560–6.
  56. Andreakos E., Tsiodras S. COVID-19: lambda interferon against viral load and hyperinflammation. EMBO Mol. Med. 2020; 12(6): e12465.
  57. Feld J.J., Kandel C., Biondi M.J., Kozak R.A., Zahoor M.A., Lemieux C., et al. Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial. Lancet Respir. Med. 2021; 9(5): 498–510.
  58. Jagannathan P., Andrews J.R., Bonilla H. et al. Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat. Commun. 2021; 12(1): 1967.
  59. Ben-Zuk N., Dechtman I.D., Henn I., Weiss L., Afriat A., Krasner E., et al. Potential prophylactic treatments for COVID-19. Viruses. 2021; 13(7): 1292.
  60. Eiger BioPharmaceuticals announces first patients dosed with peginterferon lambda in phase 3 Together study of newly diagnosed COVID-19 outpatients. Available at: (accessed January 15, 2022).
  61. COVID-19 Information. Clinical trial number NCT04331899; NCT04354259; NCT04344600; NCT04388709; NCT04534673. Available at: (accessed January 24, 2022).
  62. Tuta-Quintero E., Ayala C.M., Santos A.M. Eficacia y seguridad del peginterferón lambda para la Covid-19, indicios de un nuevo antiviral. Boletín de Malariología y Salud Ambiental. 2021; 61(2). Available at: (in Spanish) (accessed January 24, 2022).

Copyright (c) 2022 Ershov F.I., Narovlyansky A.N.

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

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС77-77676 от 29.01.2020.

This website uses cookies

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

About Cookies