Biological activity of interferons in the novel coronavirus infection COVID-19

Cover Page


Cite item

Full Text

Abstract

Introduction. The immunopathogenesis of the novel coronavirus infection COVID-19 is usually associated with the development of imbalance in the immune response to its causative agent, SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). This is manifested, in particular, by interferons’ (IFNs) deficiency at the beginning of the disease followed by hyperproduction of pro-inflammatory cytokines. The virus causes a decrease in IFN types I (α/β) and III (λ) levels; changes in IFN type II (γ) are less studied. In this regard, it is relevant to assess the functional bioactive IFN (interferon status) in COVID-19. The aim of the study was to assess the antiviral potential of the body by testing the biologically active IFNs in COVID-19.

Material and methods. We used biological serum samples of COVID-19 patients taken in the acute phase (110 patients on the 1–5 days of the disease) and during rehabilitation (47 patients during 1–3 months after the disease onset). Assessment of interferon status was performed according to the technique developed by the authors and described earlier.

Results. The IFN status of patients with COVID-19 in the acute period and in the phase of post-infection rehabilitation was studied during the observation period. It was found that SARS-CoV-2 causes a pronounced inhibition of biological activity of IFN types I and II compared to the reference values by more than 20 and 7 times, respectively. During the post-COVID period, incomplete recovery of the IFN system activity was registered, which proceeded very slowly. No cases of reaching physiological indicators of interferon status were identified during the observation period.

Conclusion. The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

About the authors

T. P. Ospelnikova

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya

Author for correspondence.
Email: ospelnikovat@mail.ru
ORCID iD: 0000-0002-1580-6096

Tatiana Рetrovna Ospelnikova, PhD (Medicine), Head of interferons laboratory

Moscow, 105064, Malyi Kazennyi pereulok, 5a

 

Россия

D. S. Levitskaya

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: dyna-s@yandex.ru
ORCID iD: 0000-0003-4316-1237

Dina Sagitovna Levitskaya -  PhD (Medicine), Senior Researcher of interferons laboratory 

Moscow, 105064

Россия

L. V. Kolodyazhnaya

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya

Email: 4583103@mail.ru
ORCID iD: 0000-0001-6725-2219

Larisa Vasil'evna Kolodyazhnaya - laboratory assistant-researcher of interferons laboratory 

 Moscow, 105064

Россия

A. D. Shitova

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: countess.iris@yandex.ru
ORCID iD: 0000-0003-0787-6251

Anna Denisovna Shitova -  Research laboratory assistant of interferons laboratory

Moscow

Россия

V. N. Osiptsov

FSBHI «Main Military Clinical Hospital of the National Guard of the Russian Federation»

Email: valeraosiptsov@gmail.com
ORCID iD: 0000-0003-1027-7620

Valery Nikolaevich Osiptsov - Senior therapist, The Main Military Clinical Hospital 

Balashikha, 143915

Россия

L. R. Arifullina

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: arifullinalidiya@gmail.com
ORCID iD: 0000-0003-4787-324X

Lidiya Rufanovna Arifullina - Research laboratory assistant of Molecular Immunology 

105064, Malyi Kazennyi pereulok,5a

Россия

N. O. Kryukova

FSAEI HE Pirogov Russian National Medical University of the Ministry of the Health of Russia (Pirogov Medical
University)

Email: kryukovanadia@gmail.com
ORCID iD: 0000-0002-8167-0959

Nadezhda Olegovna Kryukova - PhD student, Department of hospital therapy, Pediatric faculty

Moscow, 117997 Ostrovityanova street, 1

Россия

D. V. Pakhomov

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: dm_pachomov@mail.ru
ORCID iD: 0000-0002-4073-6085

Dmitry Vladimirovich Pakhomov - PhD (Medicine), Senior Researcher Laboratory of vaccine prevention and immunotherapy 

Moscow, 105064 Malyi Kazennyi pereulok, 5a

Россия

E. A. Khromova

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: kate.khromova@mail.ru
ORCID iD: 0000-0002-4003-9976

Ekaterina Alexandrovna Khromova - PhD (Medicine), Researcher, Laboratory of vaccine prevention and immunotherapy of allergic diseases

Moscow, 105064 Malyi Kazennyi pereulok, 5a

Россия

I. A. Baranova

FSAEI HE Pirogov Russian National Medical University of the Ministry of the Health of Russia (Pirogov Medical
University)

Email: iribaranova@yandex.ru
ORCID iD: 0000-0002-2469-7346

Irina Aleksandrovna Baranova - Doctor of Med Sci, Professor; Department of Hospital Therapy

Moscow, 117997 Ostrovityanova street, 1

Россия

A. G. Chuchalin

FSAEI HE Pirogov Russian National Medical University of the Ministry of the Health of Russia (Pirogov Medical
University)

Email: pulmomoskva@mail.ru
ORCID iD: 0000-0002-6808-5528

Alexander Grigor'evich Chuchalin - Doctor of Med Sci, Professor, Academician of the RAS; Department of Hospital Therapy

Moscow, 117997 Ostrovityanova street

Россия

M. P. Kostinov

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: monolit.96@mail.ru
ORCID iD: 0000-0002-1382-9403

Mikhail Petrovich Kostinov– Doctor of Med Sci, Professor, head of the Allergic Diseases Vaccinal Prevention and an Immunotherapy Laboratory

119991, Trubetskaya str., 8, bld. 2

Россия

O. A. Svitich

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: svitichoa@yandex.ru
ORCID iD: 0000-0003-1757-8389

Oxana Anatol'evna Svitich - Corresponding member of Russian Academy of Sciences, Doctor of Med Sci, Director

Moscow, 105064, Malyi Kazennyi pereulok, 5a

Россия

References

  1. Постановление Правительства РФ № 66 «О внесении изменения в перечень заболеваний, представляющих опасность для окружающих». М.; 2020.
  2. 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): 870–8. https://doi.org/10.1016/j.chom.2020.05.008
  3. COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Availible at: https://github.com/CSSEGISandData/COVID-19 (accessed 2 April 2022)
  4. Coronavirus (COVID-19) confirmed cases, new cases, recoveries, and deaths in Russia as of March 23, 2022, by federal subject. Availible at: https://www.statista.com/statistics/1102935/coronavirus-casesby-region-in-russia/ (accessed 2 April 2022).
  5. Lei X., Dong X., Ma R., Wang W., Xiao X., Tian Z., et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 2020; 11(1): 3810. https://doi.org/10.1038/s41467-020-17665-9
  6. Galani I.E., Rovina N., Lampropoulou V., Triantafyllia V., Manioudaki M., Pavlos E., et al. Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nat. Immunol. 2021; 22(1): 32–40. https://doi.org/10.1038/s41590-020-00840-x
  7. Felgenhauer U., Schoen A., Gad H.H., Hartmann R., Schaubmar A.R., Failing K., et al. Inhibition of SARS-CoV-2 by type I and type III interferons. J. Biol. Chem. 2020; 295(41): 13958–64. https://doi.org/10.1074/jbc.AC120.013788
  8. Busnadiego I., Fernbach S., Pohl M.O., Karakus U., Huber M., Trkola A., et al. Antiviral activity of type I, II, and III interferons counterbalances ACE2 inducibility and restricts SARS-CoV-2. mBio. 2020; 11(5): e01928-20. https://doi.org/10.1128/mBio.01928-20
  9. Wei L., Ming S., Zou B., Wu Y., Hong Z., Li Z., et al. Viral Invasion and Type I Interferon Response Characterize the Immunophenotypes During Covid-19 Infection. SSRN Journal. 2020. https://dx.doi.org/10.2139/ssrn.3564998 Available at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3564998 (accessed December 16, 2021).
  10. Мясников А.Л., Бернс С.А., Талызин П.А., Ершов Ф.И. Интерферон гамма в терапии пациентов с COVID-19 среднетяжелого течения. Вопросы вирусологии. 2021; 66(1) 47–54. https://doi.org/10.36233/0507-4088-24
  11. Ершов Ф.И., Оспельникова Т.П., Наровлянский А.Н. Интерфероновый статус как метод определения неспецифических биомаркеров иммунопатологии человека. Журнал микробиологии, эпидемиологии и иммунобиологии. 2019; (3): 91–9. https://doi.org/10.36233/0372-9311-2019-3-91-99
  12. Оспельникова Т.П., Морозова О.В., Андреева С.А., Исаева Е.И., Koлoдяжная Л.В., Колобухина Л.В., и др. Отличия спектров РНК интерферонов и интерферон-индуцируемого гена MX1 при гриппозной и аденовирусной инфекциях. Иммунология. 2018; 39(5-6): 290–3. http://dx.doi.org/10.18821/0206-4952-2018-39-5-6-290-293
  13. Оспельникова Т.П., Колодяжная Л.В., Табаков В.Ю., Ершов Ф.И. Способ определения продукции интерферонов как параметров врожденного иммунитета. Патент РФ №2657808; 2018. https://i.moscow/patents/RU2657808C1_20180615 (accessed December 16, 2021).
  14. Cai Y., Zhang J., Xiao T., Peng H., Sterling S.M., Walsh R.M. Jr., et al. Distinct conformational states of SARS-CoV-2 spike protein. Science. 2020; 369(6511): 1586–92. https://doi.org/10.1126/science.abd4251
  15. Thoms M., Buschauer R., Ameismeier M., Koepke L., Denk T., Hirschenberger M., et al. Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science. 2020; 369(6508): 1249–55. https://doi.org/10.1126/science.abc8665
  16. Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 2020; 11(1): 1620. https://doi.org/10.1038/s41467-020-15562-9
  17. Bullerdiek J. COVID-19 challenging cell biology. Protoplasma. 2020; 257(3): 619–20. https://doi.org/10.1007/s00709-020-01506-z
  18. Thevarajan I., Nguyen T.H.O., Koutsakos M., Druce J., Caly L., van de Sandt C.E., et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat. Med. 2020; 26(4): 453–5. https://doi.org/10.1038/s41591-020-0819-2
  19. Министерство здравоохранения Российской Федерации. Временные методические рекомендации «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)». Версия 11 (07.05.2021). Available at: https://minzdrav.gov.ru/ministry/med_covid19
  20. Lapić I., Rogić D., Plebani M. Erythrocyte sedimentation rate is associated with severe coronavirus disease 2019 (COVID-19): a pooled analysis. Clin. Chem. Lab. Med. 2020; 58(7): 1146–8. https://doi.org/10.1515/cclm-2020-0620
  21. Vabret N., Britton G.J., Gruber C., Hegde S., Kim J., Kuksin M., et al. Immunology of COVID-19: current state of the science. Immunity. 2020; 52(6): 910–41. https://doi.org/10.1016/j.immuni.2020.05.002
  22. Симбирцев А.С. Иммунопатогенез и перспективы иммунотерапии коронавирусной инфекции. ВИЧ-инфекция и иммуносупрессия. 2020; 12(4): 7–22. https://doi.org/10.22328/2077-9828-2020-12-4-7-22
  23. Ершов Ф.И. Хронология пандемии COVID-19. М.: ГЭОТАР-Медиа; 2021.
  24. Adamczyk B., Morawiec N., Arendarczyk M., Baran M., Wierzbicki K., Sowa P., et al. Multiple sclerosis immunomodulatory therapies tested for effectiveness in COVID-19. Neurol. Neurochir. Pol. 2021; 55(4): 357–68. https://doi.org/10.5603/PJNNS.a2021.0051
  25. Ivashkiv L., Donlin L. Regulation of type I interferon responses. Nat. Rev. Immunol. 2014; 14(1): 36–49. https://doi.org/10.1038/nri3581
  26. Ye L., Schnepf D., Staeheli P. Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat. Rev. Immunol. 2019; 19(10): 614–25. https://doi.org/10.1038/s41577-019-0182-z
  27. Оспельникова Т.П., Исаева Е.И., Колодяжная Л.В., Козулина И.С., Андреева С.А., Полосков В.В., и др. Противовирусная активность препаратов интерферона бета-1а. Вопросы вирусологии. 2015; 60(6): 24–8.
  28. Zhou Q., Chen V., Shannon C.P., Wei X.S., Xiang X., Wang X., et al. Interferon-α2b Treatment for COVID-19. Front. Immunol. 2020; 11: 1061. https://doi.org/10.3389/fimmu.2020.01061
  29. Pinto D., Park Y.J., Beltramello M., Walls A.C., Tortorici M.A., Bianchi S., et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020; 583(7815): 290–5. https://doi.org/10.1038/s41586-020-2349-y
  30. Neufeldt C.J., Cerikan B., Cortese M., Frankish J., Lee J.Y., Plociennikowska A., et al. SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB. Commun. Biol. 2022; 5(1): 45. https://doi.org/10.1038/s42003-021-02983-5
  31. 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. https://doi.org/10.1126/sciimmunol.abd1554
  32. Stertz S., Reichelt M., Spiegel M., Kuri T., Martínez-Sobrido L., García-Sastre A., et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology. 2007; 361(2): 304–15. https://doi.org/10.1016/j.virol.2006.11.027
  33. Chen Y., Cai H., Pan J., Xiang N., Tien P., Ahola T., et al. Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. Proc. Natl. Acad. Sci. USA. 2009; 106: 3484–9. https://doi.org/10.1073/pnas.0808790106
  34. Menachery V.D., Yount B.L. Jr., Josset L., Gralinski L.E., Scobey T., Agnihothram S., et al. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 20-o-methyltransferase activity. J. Virol. 2014; 88(8): 4251–64. https://doi.org/10.1128/JVI.03571-13
  35. Lokugamage K.G., Hage A., Schindewolf C., Rajsbaum R., Menachery V.D. SARS-CoV-2 is sensitive to type I interferon pretreatment. bioRxiv. 2020. Preprint. https://doi.org/10.1101/2020.03.07.982264

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2022 Ospelnikova T.P., Levitskaya D.S., Kolodyazhnaya L.V., Shitova A.D., Osiptsov V.N., Arifullina L.R., Kryukova N.O., Pakhomov D.V., Khromova E.A., Baranova I.A., Chuchalin A.G., Kostinov M.P., Svitich O.A.

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