The role of IL-6 receptor inhibitor treatment in critical patient monitoring with COVID-19

Objectives: The COVID-19 disease can manifest itself with acute respiratory distress syndrome, renal failure, and septic shock in critically ill patients. There are opinions that there is a correlation between high IL-6 levels and disease severity. In our intensive care unit, we evaluated the changes in the laboratory data and radiological involvement severity of our patients who underwent tocilizumab treatment and examined the appropriate laboratory parameter in the treatment follow-up and its effect on survival.

Methods: In the critical patient follow-up of COVID-19, 17 of the 23 patients treated with tocilizumab had a mortal course (Group 1) and the remaining 6 (Group 2) were. The C-reactive protein, lactate dehydrogenase, IL-6, D-dimer, procalcitonin, albumin, and ferritin values, which were routinely screened in our clinic on the day of tocilizumab treatment and the 5th day after, were recorded. Both the change between the two groups and the change between days 1 and 5 were analyzed.

Results: A total of 23 patients (55.35 ± 13.31 years) were included in the study. The computed tomography severity score assessed at the intensive care unit admission was statistically significantly higher in Group 2. The procalcitonin and lactate dehydrogenase values measured on day 5 after tocilizumab were significantly lower in Group 2. On the 5th day after treatment, the levels of C-reactive protein, ferritin, chest X-rays, IL-6 and D-dimer statistically significantly changed compared to the first day of the treatment. In correlation with the decrease in PCT as of the 5th day after tocilizumab administration, an increasing tendency was observed in 28-day survival.

Conclusion: This study demonstrated that tocilizumab treatment may positively contribute to the treatment by decreasing cytokine levels. PCT and LDH follow-up before and after treatment in critically ill patients who are receiving tocilizumab treatment can give an idea about survival.

Coronavirus; IL-6 receptor inhibitor; Intensive care units; Tocilizumab; LDH; PCT; CRP

[1] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020; 395: 507–513.

[2] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppres-sion. The Lancet. 2020; 395: 1033–1034.

[3] Aziz M, Fatima R, Assaly R. Elevated interleukin‐6 and severe COVID-19: a meta-analysis. Journal of Medical Virology. 2020; 92: 2283–2285.

[4] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020; 395: 1054–1062.

[5] Zhang S, Li L, Shen A, Chen Y, Qi Z. Rational use of tocilizumab in the treatment of novel coronavirus pneumonia. Clinical Drug Investigation. 2020; 40: 511–518.

[6] Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, et al. Association between early treatment with tocilizumaband mortality among critically ill patients with COVID-19. JAMA Internal Medicine. 2021;181: 41–51.

[7] Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalizedpatientswith severe COVID-19 pneumonia. The New England Journal of Medicine. 2021. (in press)

[8] Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with COVID-19 pneumonia. New England Journal of Medicine. 2021; 384: 20–30.

[9] Genentech. Prescribing information. ACTEMRA® (tocilizumab) injection, for intravenous or subcutaneous use. 2019. Available at: https://www.gene.com/download/pdf/actemra_prescribing. pdf (Accessed: 11 March 2020).

[10] Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, Arabi YM, et al. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. The New England Journal of Medicine. 2021. (in press)

[11] Tung-Chen Y, Martí de Gracia M, Díez-Tascón A, Alonso-González R, Agudo-Fernández S, Parra-Gordo ML, et al. Correlation between chest computed tomography and lung ultrasonography in patients with coronavirus disease 2019 (COVID-19). Ultrasound in Medicine & Biology. 2020; 46: 2918–2926.

[12] Zhang R, Ouyang H, Fu L, Wang S, Han J, Huang K, et al. CT features of SARS-CoV-2 Pneumonia according to clinical presentation: a retrospective analysis of 120 consecutive patients from Wuhan city. European Radiology. 2020; 30: 4417–4426.

[13] De Wever W, Meersschaert J, Coolen J, Verbeken E, Verschakelen JA. The crazy-paving pattern: a radiological-pathological correlation. Insights into Imaging. 2011; 2: 117–132.

[14] Pan F, Ye T, Sun P, Gui S, Liang B, Li L, et al. Time course of lung changes at chest ct during recovery from coronavirus disease 2019 (COVID-19). Radiology. 2020; 295: 715–721.

[15] Geaorge D, Marrey P. IBM SPSS statistics 25 step by step: a simple guide and reference. 15th edition. NY: Routledge. 2018.

[16] Lan S, Lai C, Huang H, Chang S, Lu L, Hsueh P. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. International Journal of Antimicrobial Agents. 2020; 56: 106103.

[17] Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Internal Medicine. 2020; 180: 1345.

[18] Chiaretti A, Pulitanò S, Barone G, Ferrara P, Romano V, Capozzi D, et al. IL-1 β and IL-6 upregulation in children with H1N1 influenza virus infection. Mediators of Inflammation. 2013; 2013: 495848.

[19] Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: a single center experience. Journal of Medical Virology. 2020; 92: 814–818.

[20] Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008; 112: 3959–3964.

[21] Toniatia P, Pivab S, Cattalinid M, Garrafaf E, Regolaa F, CastellieF, et al. Tocilizumab for the treatment of severe COVID-19 Pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmunity Reviews. 2020; 19: 102568.

[22] Liu T, Zhang J, Yang Y, Ma H, Li Z, Zhang J, et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. medRxiv. 2020. (in press)

[23] Moreno-Pérez O, Andres M, Leon-Ramirez J, Sánchez-Payá J, Rodríguez JC, Sánchez R, et al. Experience with tocilizumab in severe COVID-19 Pneumonia after 80 days of follow-up: a retrospective cohort study. Journal of Autoimmunity. 2020; 114: 102523.

[24] Hanley B, Lucas SB, Youd E, Swift B, Osborn M. Autopsy in suspected COVID-19 cases. Journal of Clinical Pathology. 2020; 73: 239–242.

[25] Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological find-ings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. 2020; 8: 420–422.

[26] McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmunity Reviews. 2020; 19: 102537.

[27] Ruscitti P, Berardicurti O, Di Benedetto P, Cipriani P, Iagnocco A, Shoenfeld Y, et al. Severe COVID-19, another piece in the puzzle of the hyperferritinemic syndrome. An immunomodulatory perspective to alleviate the storm. Frontiers in Immunology. 2020; 11: 1130.

[28] Duan K, Liu B, Li C, Zhang H, Yu T, QuJ, et al. The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study. medRxiv. 2020. (in press)

[29] Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of

convalescent plasmatherapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. The Journal of the American Medical Association. 2020; 324: 460-470.