Clinical and immunological characteristics of the postcovid period in patients with moderate-severe COVID-19 who received therapy with the inclusion of an IL-6 receptor antagonist
AbstractIntroduction. Significant progress in clinical research has led to a better understanding of the pathogenesis of COVID-19, contributing to its more effective therapy. The revealed key role of IL-6 in the development and intensification of the «cytokine storm», which has received reliable pathophysiological and pharmacological justification, supports the use of therapeutic strategies aimed at IL-6 or its receptor. Nevertheless, the changes that occur in the immune system after COVID-19 are of interest for a better understanding of the mechanisms of the formation of postcovid syndrome in patients receiving therapy with the inclusion of IL-6 receptor antagonists, its pathogenesis and the search for targets for further therapeutic effects.
The aim of the study – to study the clinical and immunological parameters of patients who underwent a moderate-severe variant of COVID-19 and received therapy with the inclusion of IL-6 receptor antagonist during treatment and 6 months after discharge/recovery.
Material and methods. 30 hospitalized patients were examined with the diagnosis: COVID-19, moderate-severe 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 at discharge, as well as 6 months after discharge from the hospital, in addition, the quality of life was assessed 6 months after the COVID-19.
Results. Postcovid syndrome in patients who have undergone COVID-19 in a moderate-severe form manifests itself in a number of symptoms – decreased appetite, weakness, sleep disorders, depression, headache, shortness of breath, cough, tachycardia, dizziness. In addition, there is an exacerbation of chronic diseases that requires correction in planned therapy. 6 months after discharge from the hospital, there is an increase in CRP and fibrinogen levels, which most likely also reflects the deterioration of the course of concomitant pathology. There is an increase in the level of T-lymphocytes, as well as a decrease in the level of B-lymphocytes.
Conclusion. Patients who had COVID-19 require dynamic follow-up. In patients with a moderate-severe form of COVID-19 who received complex therapy with the inclusion of monoclonal antibodies to IL-6 receptors, dexamethasone, antiviral therapy, anticoagulants, oxygen therapy, there are dysregulatory processes in the immune system that persist 6 months after recovery.
Keywords:coronavirus infection; COVID-19; targeted therapy; IL-6 inhibitors; cytokine storm; postcovid syndrome
For citation: Sizyakina L.P., Skripkina N.A., Antonova E.A., Sizyakin D.V. Clinical and immunological characteristics of the postcovid period in patients with moderate-severe COVID-19 who received therapy with the inclusion of an IL-6 receptor antagonist. Immunologiya. 2022; 43 (5): 606–14. DOI: https://doi.org/10.33029/0206-4952-2022-43-5-606-614 (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.; the final version and the integrity of the text – Sizyakina L.P.
References
1. Jones S.A., Hunter C.A. Is IL-6 a key cytokine target for therapy in COVID-19? Nat. Rev. Immunol. 2021; 21 (6): 337–9. DOI: https://doi.org/10.1038/s41577-021-00553-8
2. Kim J.S., Lee J.Y., Yang J.W., et al. Immunopathogenesis and treatment of cytokine storm in COVID-19. Theranostics. 2021; 11 (1): 316–29. DOI: https://doi.org/10.7150/thno.49713
3. Kostinov M.P., Markelova E.V., Svitich O.A., Polishchuk V.B. Immune mechanisms of SARS-CoV-2 and potential drugs in the prevention and treatment of COVID-19. Pul’monologiya. 2020; 30 (5): 700–8. DOI: https://doi.org/10.18093/0869-0189-2020-30-5-700-708 (in Russian)
4. Wang J., Jiang M., Chen X., Montaner L.J. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J. Leukoc. Biol. 2020; 108 (1): 17–41. DOI: https://doi.org/10.1002/JLB.3COVR0520-272R
5. Temporary guidelines «Prevention, diagnosis and treatment of a new coronavirus infection (2019-nCoV)» of the Ministry of Health of the Russian Federation. Version 15 (22.02.2022). (in Russian)
6. Pelaia C., Calabrese C., Garofalo E., Bruni A., Vatrella A., Pelaia G. Therapeutic role of tocilizumab in SARS-CoV-2-induced cytokine storm: rationale and current evidence. Int. J. Mol. Sci. 2021; 22 (6): 3059. DOI: https://doi.org/10.3390/ijms22063059
7. Mohammed R.N., Tamjidifar R., Rahman H.S., et al. A comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19) [published correction appears in Cell Commun. Signal. 2022; 20 (1): 90]. Cell Commun. Signal. 2022; 20 (1): 79. DOI: https://doi.org/10.1186/s12964-022-00856-w
8. Yong S.J. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect. Dis. (Lond.). 2021; 53 (10): 737–54. DOI: https://doi.org/10.1080/23744235.2021.1924397
9. Altmann D.M., Boyton R.J. Decoding the unknowns in long COVID. BMJ. 2021; 372: n132. DOI: https://doi.org/10.1136/bmj.n132
10. Chippa V., Aleem A., Anjum F. Post acute coronavirus (COVID-19) syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing, May 4, 2022.
11. Wang Y., Wu M., Li Y., et al. The effects of SARS-CoV-2 infection on modulating innate immunity and strategies of combating inflammatory response for COVID-19 therapy. J. Biomed. Sci. 2022; 29: 27. DOI: https://doi.org/10.1186/s12929-022-00811-4
12. 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)
13. Sizyakina L.P., Skripkina N.A., Antonova Е.А., Zakurskaya V.Y., Sizyakin D.V. Dynamics of immune status parameters in patients with COVID-19 with targeted blockade of IL-6 receptors. Immunologiya. 2022; 43 (2): 188–96. DOI: https://doi.org/10.33029/0206-4952-2022-43-2-188-196 (in Russian)
14. Fomina D., Lysenko M.A., Beloglazova I.P., Mutovina Z.Y., Poteshkina N.G., Samsonova I.V., Kruglova T.S., Chernov A.A., Karaulov A.V. Temporal clinical and laboratory response to interleukin-6 receptor blockade with tocilizumab in 89 hospitalized patients with COVID-19 pneumonia. Pathog Immun. 2020; 5 (1): 327–41. DOI: https://doi.org/10.20411/pai.v5i1.392