Background: Tocilizumab (TCZ), a monoclonal antibody against the most prevalent cytokine interleukin-6 (IL-6), is an emerging therapeutic option for COVID-19 infections. The present study was undertaken to assess the therapeutic response of TCZ therapy in severely or critically ill COVID-19 patients and its role as an effective modality of management. Methods: The present retrospective observational study included 30 admitted severely or critically ill COVID-19 patients, treated with TCZ therapy on behalf of raised IL-6 levels. The patients’ data concerning medical history, clinical manifestation, arterial blood gas analysis, mode of oxygenation, radiological imaging, and outcome were extracted from their medical records and compared pre- and post-TCZ infusion. Results: All patients of the study group had symptomatic presentations with a mean PaO2/FiO2 (P/F) ratio of 205.41 before TCZ infusion. All patients had a raised IL-6 level (mean value 206.56 pg/mL) that was extremely elevated in 90% of patients. Infusion of TCZ dramatically reduced mean body temperature (100.78–99.32°F) and the requirement for supplemental oxygen (68–48%) and improved mean SpO2 (86–89%) and mean P/F ratio (208–240) within 24 hours. Three patients on noninvasive ventilation were weaned off after TCZ infusion. Serum levels of IL-6 were raised initially but declined within 3–5 days of post-TCZ infusion. Conclusion: TCZ appears to be an effective therapeutic option in severely or critically ill COVID-19 patients with raised IL-6 levels. TCZ immediately improves the clinical status of patients by a probable mechanism of inhibition of cytokine storm and reduces COVID-19-related mortalities.
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. Lancet 2020;395(10223):507–513. DOI: 10.1016/S0140-6736(20)30211-7.
Hui DS, Azhar EI, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health—the latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 2020;91:264–266. DOI: 10.1016/j.ijid.2020.01.009. PMC 7128332. PMID 31953166.
Murthy S, Gomersall CD, Fowler RA. Care for critically ill patients with COVID19. JAMA 2020;323(15):1499–1500. DOI: 10.1001/jama.2020. 3633.
Lan J, Ge JW, Yu JF, Shan SS, Zhou H, Fan SL, et al. Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor. 2020. Available from: https://www.biorxiv.org/content/10.1101/2020.02.19.956235v1. DOI: 10.1101/2020.02.19. 956235.
Davies R, Choy E. Clinical experience of IL-6 blockade in rheumatic diseases–implications on IL-6 biology and disease pathogenesis. Semin Immunol 2014;26(1):97–104. DOI: 10.1016/j.smim.2013.12.002.
Wolf J, Rose-John S, Garbers C. Interleukin-6 and its receptors: a highly regulated and dynamic system. Cytokine 2014;70(1):11–20. DOI: 10.1016/j.cyto.2014.05.024.
Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest 2011;121(9):3375–3383. DOI: 10.1172/JCI57158.
Kaly L, Rosner I. Tocilizumab—a novel therapy for non-organ-specific autoimmune diseases. Best Pract Res Clin Rheumatol 2012;26(1):157–165. DOI: 10.1016/j.berh.2012.01.001.
Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis 2020;34:101623. DOI: 10.1016/j.tmaid.2020.101623.
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: a single center experience. J Med Virol 2020;92(7):814–818. DOI: 10.1002/jmv.25801.
Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis 2020:ciaa449. Available from: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa449/5821311 by guest on 01 June 2020. DOI: 10.1093/cid/ciaa449.
Kotch C, Barrett D, Teachey DT. Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome. Expert Rev Clin Immunol 2019;15(8):813–822. DOI: 10.1080/1744666X.2019.1629904.
Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020;55(5):105954. DOI: 10.1016/j.ijantimicag.2020.105954.
Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020;117(20):10970–10975. DOI: 10.1073/pnas.2005615117.
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(10):3959–3964. DOI: 10.1182/blood-2008-05-155846.