COMPARISON OF EPIDEMIOLOGICAL AND CLINICAL PARAMETERS IN PATIENTS WITH SEVERE COVID 19 TREATED WITH AND WITHOUT TOCILIZUMAB
Abstract
Cytokine storm is an uncontrolled immune response in the immunopathogenic mechanism of COVID 19, similar to that of severe influenza. Inflammatory cytokines including: TNF-α, IL-6, IL-8, IL-12, are released in large amounts during of disease progression, causing potential Acute Respiratory Distress Syndrome (ARDS), Hemophagocytic Lymphohistiocytosis (HLH) and Multi-Organ Dysfunction (MOFS). Tocilizumab is an immunosuppressive drug that is used in the treatment of Rheumatoid Arthritis and Systemic Juvenile Idiopathic Arthritis in children. As a human monoclonal antibody targeting Interleukin 6 receptors (IL-6R), it interrupts its action in the cytokine storm and thereby reduces vascular permeability and increased passage of fluid and blood elements into the alveoli that would lead to severe respiratory distress (ARDS). To evaluate the effect of Tocilizumab treatment in patients with severe form of COVID-19. This retrospective study included 213 patients with a severe form of COVID-19 divided into 2 groups: Group 1 of 131 male and female patients who received Cytokine storm is an uncontrolled immune response in the immunopathogenic mechanism of COVID 19, similar to that of severe influenza. Inflammatory cytokines including: TNF-α, IL-6, IL-8, IL-12, are released in large amounts during of disease progression, causing potential Acute Respiratory Distress Syndrome (ARDS), Hemophagocytic Lymphohistiocytosis (HLH) and Multi-Organ Dysfunction (MOFS). Tocilizumab is an immunosuppressive drug that is used in the treatment of Rheumatoid Arthritis and Systemic Juvenile Idiopathic Arthritis in children. As a human monoclonal antibody targeting Interleukin 6 receptors (IL-6R), it interrupts its action in the cytokine storm and thereby reduces vascular permeability and increased passage of fluid and blood elements into the alveoli that would lead to severe respiratory distress (ARDS). To evaluate the effect of Tocilizumab treatment in patients with severe form of COVID-19. This retrospective study included 213 patients with a severe form of COVID-19 divided into 2 groups: Group 1 of 131 male and female patients who received Tocilizumab and Group 2 of 82 male and female patients who did not receive tocilizumab. Patients who received tocilizumab had a significantly shorter stay in the intensive care unit compared to patients who did not received tocilizumab (p=0.021). A significantly lower mortality was registered in patients who were treated with Tocilizumab . This retrospective case control study showed that treatment with Tocilizumab as a human monoclonal antibody in patients with severe form of COVID-19 can lead to shorter hospital stay and reduced mortality compared to patients who did not receive Tocilizumab.
Keywords: Cytokine storm, Tocilizumab, COVID 19, Interleukin 6, ARDS.
References
2. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4. doi: 10.1016/j.jaci.2020.05.008. Epub 2020 May PMID: 32425269; PMCID: PMC7233239.
3. Sheppard, M. et al. (2017) ‘Tocilizumab ( Actemra )’, Human Vaccines & Immunotherapeutics, 13(9), pp. 1972–1988. doi: 10.1080/21645515.2017.1316909.
4. Guidance, L. (2021) ‘Living guidance for clinical management of COVID-19’, (November).WHO
5. 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;395:1054–62.
6. Vanderheiden A, Ralfs P, Chirkova T, Upadhyay AA, Zimmerman MG, Bedoya S, et al. Type I and Type III interferons restrict SARS-CoV-2 infection of human airway epithelial cultures. J Virol. 2020;94:382–727.
7. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395:497–506.
8. Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020;40:37.
9. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020;8:e46–7.
10. Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol.
11. Menzella F, Fontana M, Salvarani C, Massari M, Ruggiero P, Scelfo C, et al. Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation. Crit Care. 2020;24:589.
12. Klopfenstein. T. et al. (2020) ‘Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients’, Medecine et Maladies Infectieuses, 50(5), pp. 397–400. doi: 10.1016/j.medmal.2020.05.001.
13. Capra, R. et al. (2020) ‘Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia’, European Journal of Internal Medicine, 76(May), pp. 31–35. doi: 10.1016/j.ejim.2020.05.009.
14. Menzella, F., Fontana, M., Salvarani, C. et al. Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation. Crit Care 24, 589 (2020). https://doi.org/10.1186/s13054-020-03306-6
15. Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, Franceschini E, Cuomo G, Orlando G, Borghi V, Santoro A, Di Gaetano M, Puzzolante C, Carli F, Bedini A, Corradi L, Fantini R, Castaniere I, Tabbì L, Girardis M, Tedeschi S, Giannella M, Bartoletti M, Pascale R, Dolci G, Brugioni L, Pietrangelo A, Cossarizza A, Pea F, Clini E, Salvarani C, Massari M, Viale PL, Mussini C. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug;2(8):e474-e484. doi: 10.1016/S2665-9913(20)30173-
16. Somers, E. C. et al. (2021) ‘Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19’, 73, pp. 445–454. doi: 10.1093/cid/ciaa954.
17. Biran, N. et al. (no date) ‘Tocilizumab among patients with COVID-19 in the intensive care unit : a multicentre observational study’, The Lancet Rheumatology, 2(10), pp. e603–e612. doi: 10.1016/S2665-9913(20)30277-0.
