2 . 2022

Dynamics of immune status parameters in patients with COVID-19, receiving therapy with inclusion of an IL-6 receptor antagonist

Abstract

Introduction. Timely prescribing of proactive cytokine storm therapy in patients with COVID-19 using targeted therapy is an important component of success in the treatment of this disease. However, the blockade of receptors to proinflammatory cytokines, in particular to IL-6, leads to shifts in immunoregulatory processes, the nature of which can determine the effectiveness of the therapy and the course of the postCOVID period of rehabilitation of the patient.

The aim of the study – to study the dynamics of the parameters of innate and adaptive immunity in a patient with COVID-19 using an IL-6 receptor anatagonist.

Material and methods. 30 hospitalized patients were examined with the diagnosis: COVID-19 coronavirus infection (confirmed), moderate form; complication: bilateral polysegmental pneumonia. The comparison group consisted of practically healthy donors (30 people). The dynamics of laboratory parameters (general clinical, biochemical and immunological) were evaluated against the background of therapy with IL-6 blockers.

Results. The presence of lymphopenia in the patient, an increase in the level of CRP, LTK, fibrinogen, lactate, IL-6 require the use of proactive anti-cytokine therapy. The timely administration of these drugs (in particular, the IL-6 receptor inhibitor) has a positive effect on the course of the disease and the recovery of patients. In the immune system, after the introduction of monoclonal antibodies to IL-6 receptors, 2 weeks after administration, there is an increase in the maturation of T-lymphocytes, documented by an increase in the content of T-lymphocytes with helper function with a simultaneous decrease in the number of natural killers, B-lymphocytes and disimmunoglobulinemia of IgA, IgM and IgG classes.

Conclusion. The use of monoclonal antibodies to IL-6 receptors in patients with a moderate form of COVID-19 leads to dysregulatory processes in the immune system with their gradual normalization by 2 weeks after administration.

Keywords:coronavirus infection; COVID-19; target therapy; IL-6 receptor anatagonist; cytokine storm

For citation: Sizyakina L.P., Skripkina N.A., Antonova E.A., Zakurskaya V.Ya, Sizyakin D.V. Dynamics of immune status parameters in patients with COVID-19, receiving therapy with inclusion of an IL-6 receptor antagonist. Immunologiya. 2022; 43 (2): 188–96. DOI: https://doi.org/10.33029/0206-4952-2022-43-2-188-196 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

Authors contribution. Research concept and design – Sizyakina L.P.; collection and processing of material – Skripkina N.A., Antonova E.A., Sizyakin D.V.; text writing, editing – Skripkina N.A., Zakurskaya V.Ya.; the final version and the integrity of the text – Sizyakina L.P.

References

1. Khorobrykh Т.V., Makhnach G.K., Volgin M.V., Khorobrykh V.V., Mishchenko N.P., Ivashchenko A.A., Loginov V.G., Yakubova E.V. Clinical and immunological correlations in COVID-19: experience of immunomodulatory therapy. Immunologiya. 2021; 42 (4): 376–84. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-376-384 (in Russian)

2. Gudima G.O., Khaitov R.M., Kudlay D.A., Khaitov M.R. Molecular immunological aspects of diagnostics, prevention and treatment of coronavirus infection. Immunologiya. 2021; 42 (3): 198–210. DOI: https://doi.org/10.33029/0206-4952-2021-42-3-198-210 (in Russian)

3. Parasher A. COVID-19: current understanding of its pathophysiology, clinical presentation and treatment. Postgrad. Med. J. 2021; 97 (1147): 312–20. DOI: https://doi.org/10.1136/postgradmedj-2020-138577

4. Soy M., Keser G., Atagündüz P., et al. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin. Rheumatol. 2020; 39: 2085–94. DOI: https://doi.org/10.1007/s10067-020-05190-5

5. Bivona G., Agnello L., Ciaccio M. Biomarkers for prognosis and treatment response in COVID-19 patients. Ann. Lab. Med. 2021; 41 (6): 540–8. DOI: https://doi.org/10.3343/alm.2021.41.6.540

6. Sizyakina L.P., Zakurskaya V.Yа., Skripkina N.A., Antonova E.A. Ferritin level as a predictor of COVID-19 severe course. Immunologiya. 2021; 42 (5): 518–25. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-518-525 (in Russian)

7. Alizadehsani R., Alizadeh Sani Z., Behjati M., Roshanzamir Z., Hussain S., Abedini N., Hasanzadeh F., Khosravi A., Shoeibi A., Roshanzamir M., Moradnejad P., Nahavandi S., Khozeimeh F., Zare A., Panahiazar M., Acharya U.R., Islam S. Risk factors prediction, clinical outcomes, and mortality in COVID-19 patients. J. Med. Virol. 2021; 93 (4): 2307–20. DOI: https://doi.org/10.1002/jmv.26699

8. Kim J.S., Lee J.Y., Yang J.W., Lee K.H., Effenberger M., Szpirt W., Kronbichler A., Shin J.I. Immunopathogenesis and treatment of cytokine storm in COVID-19. Theranostics. 2021; 11 (1): 316–29. DOI: https://doi.org/10.7150/thno.49713

9. Temporary guidelines «Prevention, diagnosis and treatment of a new coronavirus infection (2019-nCoV)» of the Ministry of Health of the Russian Federation. Version 13.1 (09.11.2021) (in Russian)

10. Du P., Geng J., Wang F., Chen X., Huang Z., Wang Y. Role of IL-6 inhibitor in treatment of COVID-19-related cytokine release syndrome. Int. J. Med. Sci. 2021; 18 (6): 1356–62. DOI: https://doi.org/10.7150/ijms.53564

11. Kalashnikova T.A., Yakovlev A.A., Sizyakina L.P. Characteristics of the immune status in patients with Crohn’s disease during therapy with Infliximab. Immunologiya. 2016; 37 (1): 22–5. DOI: https://doi.org/10.18821/0206-4952-2016-37-1-22–25 (in Russian)

12. Tanaka T., Narazaki M., Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspect. Biol. 2014; 6 (10): a016295. DOI: https://doi.org/10.1101/cshperspect.a016295

13. Hirano T., Akira S., Taga T., Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol. Today. 1990; 11 (12): 443–9.

14. Kumar M., Al Khodor S. Pathophysiology and treatment strategies for COVID-19. J. Transl. Med. 2020; 18 (1): 353. DOI: https://doi.org/10.1186/s12967-020-02520-8

15. Tharmarajah E., Buazon A., Patel V., Hannah J.R., Adas M., Allen V.B., Bechman K., Clarke B.D., Nagra D., Norton S., Russell M.D., Rutherford A.I., Yates M., Galloway J.B. IL-6 inhibition in the treatment of COVID-19: a meta-analysis and meta-regression. J. Infect. 2021; 82 (5): 178–85. DOI: https://doi.org/10.1016/j.jinf.2021.03.008

16. Arkatkar T., Du S.W., Jacobs H.M., Dam E.M., Hou B., Buckner J.H., Rawlings D.J., Jackson S.W. B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity. J. Exp. Med. 2017; 214 (11): 3207–17. DOI: https://doi.org/10.1084/jem.20170580

17. Andreev I.V., Nechay K.O., Andreev A.I., Zubaryova A.P., Esaulova D.R., Alenova A.M., Nikolaeva I.A., Chernyavskaya O.P., Lomonosov K.S., Shul’zhenko A.E., Kurbacheva O.M., Latysheva E.A., Shartanova N.V., Nazarova E.V., Romanova L.V., Cherchenko N.G., Smirnov V.V., Averkov O.V., Martynov A.I., Vechorko V.I., Gudima G.O., Kudlay D.A., Khaitov M.R., Khaitov R.M. Post-vaccination and post-infection humoral immune response to the SARS-CoV-2 infection. Immunologiya. 2022; 43 (1): 18–32. DOI: https://doi.org/10.33029/0206-4952-2022-43-1-18-32 (in Russian)

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

JOURNALS of «GEOTAR-Media»