The use of prognostic scales to assess the effectiveness of the use of anti-cytokine drugs in patients with moderate and severe course of a new coronavirus infection

The aim. To analyze the effectiveness of the use of anti-cytokine drugs (tocilizumab, olokizumab and sarilumab) in a single-center retrospective cohort study based on the prediction of clinical outcomes using prognostic scales, with a single administration in patients with moderate to severe course of a new coronavirus infection.

Materials and methods. The retrospective cohort study included three groups of patients with single administration of tocilizumab (65 patients), olokizumab (56 patients) and sarilumab (26 patients). All patients were treated in a repurposed infectious diseases hospital for patients with COVID-19 on the basis of Аlexandro-Mariinskaya Regional Clinical Hospital in the period January- August 2021. Upon admission to the hospital and 2 days after administration of the drug, patients were predicted the severity of the course and outcome using prognostic scales: 4C Mortality Score, COVID-GRAM, SHOCS-COVID.

Results. A comparative analysis of the effectiveness of the use of anti-cytokine drugs using the 4C Mortality Score scale revealed a further deterioration in the prognosis of clinical outcome in the groups receiving tocilizumab (p = 0,002) and sarilumab (p = 0,031). When using the COVID-GRAM predictive scale, further deterioration of the prognosis was also noted in the tocilizumab (p = 0,004) and olokizumab (p = 0,005) groups. The SHOCS-COVID scale showed a further deterioration in the prognosis in the tocilizumab group (p = 0,001).

Conclusion. The use of drugs based on monoclonal antibodies against IL-6 and its receptors in patients with moderate to severe COVID-19 did not reveal significant positive dynamics in changing the prognosis of clinical outcome 2 days after administration of these drugs.

1. Kantemirova B. I., Vasilkova V. V. Polymorphism of genes in patients with new coronavirus infection COVID-19. Infektsionnye bolezni: novosti, mneniya, obuchenie = Infectious Diseases: News, Opinions, Training. 2022; 11 (3): 130–137. (In Russ.). doi: 10.33029/2305-3496-2022-11-3-130-137.

2. Ferrara J. L. Cytokine dysregulation as a mechanism of graft versus host disease. Current Opinion in Immunology. 1993; 5 (5): 794–799. doi: 10.1016/0952-7915(93)90139-j.

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

4. Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. Journal of Biological Regulators and Homeostatic Agents. 2020; 34 (2): 327–331. doi: 10.23812/CONTI-E.

5. Moradian N., Gouravani M., Salehi M. A., Heidari A., Shafeghat M., Hamblin M. R., Rezaei N. Cytokine release syndrome: inhibition of pro-inflammatory cytokines as a solution for reducing COVID-19 mortality. European cytokine network. 2020; 31 (3): 81–93. https://doi.org/10.1684/ecn.2020.0451.

6. Le R. Q., Li L., Yuan W., Shord S. S., Nie L., Habtemariam B.A., Przepiorka D., Farrell A. T., Pazdur R. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. Oncologist. 2018; 23 (8): 943–947. doi:10.1634/theoncologist.2018-0028.

7. 4C Mortality Score Scale. URL: https://www.mdcalc.com/calc/10338/4c-mortality-score-covid-19.

8. COVID-GRAM Scale. URL: https://www.mdcalc.com/calc/10303/covid-gram-critical-illness-risk-score.

9. Mareev V. Yu., Begrambekova Yu. L., Mareev Yu. V. How evaluate results of treatment in patients with COVID-19. Symptomatic Hospital and Outpatient Clinical Scale for COVID-19 (SHOCS–COVID). Kardiologiia = Cardiology. 2020; 60 (11): 35–41. (In Russ.).

10. COVID-19 Treatment. URL: https://www.covid19treatmentguidelines.nih.gov/.

11. COVID-19 rapid guideline: Managing COVID-19. URL: https://www.nice.org.uk/guidance/ng191/resources/covid19-rapid-guideline-managing-covid19-pdf-51035553326.

12. Knight S. R., Ho A., Pius R., Buchan I., Carson G., Drake T. M., Dunning J., Fairfield C. J., Gamble C., Green C. A., Gupta R., Halpin S., Hardwick H. E., Holden K. A., Horby P. W., Jackson C., Mclean K. A., Merson L., NguyenVan-Tam J. S., Norman L., Noursadeghi M., Olliaro P. L., Pritchard M. G., Russell C. D., Shaw C. A., Sheikh A., Solomon T., Sudlow C., Swann O. V., Turtle L. C., Openshaw P. J., Baillie J. K., Semple M. G., Docherty A. B., Harrison E. M.; ISARIC4C investigators. Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score. BMJ. 2020; 370. doi: 10.1136/bmj.m3339.

13. Liang W., Liang H., Ou L., Chen B., Chen A., Li C., Li Y., Guan W., Sang L., Lu J., Xu Y., Chen G., Guo H., Guo J., Chen Z., Zhao Y., Li S., Zhang N., Zhong N., He J.; China Medical Treatment Expert Group for COVID-19. Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. JAMA Intern Med. 2020; 180 (8): 1081–1089. doi: 10.1001/jamainternmed.2020.2033.

14. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021; 397 (10285): 1637–1645. doi: 10.1016/S01406736(21)00676-0.

15. Yang C, Zhao H. Tocilizumab in COVID-19 therapy: who benefits, and how? Lancet. 2021; 398 (10297): 299. doi: 10.1016/S0140-6736(21)01380-5.