Main Article Content

Muhammad Thifan Satyagraha
Graceanne Sheridan
Vito Etenio Ade Laryan
Gibran Chandra Syarif Hidayatullah


Acute respiratory distress syndrome (ARDS) as a clinical manifestation of severe pneumonia is a major cause of death for patients with coronavirus disease 2019 (COVID-19) who are treated in intensive care units (ICU). ARDS is triggered by cytokine storm. Cytokine storm is characterized by an increased in proinflammatory cytokines such as IL-6, IL-1α, and IL-1β. Thus, IL-6 and IL-1 cytokine inhibitors in the form of monoclonal antibodies are needed to overcome this. This review of the scientific literature aims to identify the effect of monoclonal antibody therapy, which is focusing on the inhibitors of cytokines IL-6 (tocilizumab) and IL-1 (anakira) in patients with severe pneumonia caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) ) with clinical manifestations in the form of ARDS. The design used in the form of scientific literature review. Articles were collected via Google Scholar search engine through several data sources (Pubmed, Sciencedirect, Nature, Proquest, and Springer Link). Inclusion criteria used were literature sources published between 2011 – 2020  in the form of research articles, systematic reviews, annual reports, and/or books. Meanwhile, the exclusion criterion used was literature sources under 2011. Based on article search results, tocilizumab can efficiently improve clinical status and reduce the mortality rate of COVID-19 patients with ARDS. Even so, tocilizumab can increase the risk of infection and the evidence obtained by the authors was not enough to support the administration of tocilizumab outside of clinical trials. Thus, the safety and side effects of monoclonal antibodies need to be further investigated.

Article Details

How to Cite
Satyagraha, M., Sheridan, G., Laryan, V., & Hidayatullah, G. (2022). TOCILIZUMAB AS MONOCLONAL ANTIBODY THERAPY IN OVERCOMING ACUTE RESPIRATORY DISTRESS SYNDROME IN COVID-19 PATIENTS. JIMKI: Jurnal Ilmiah Mahasiswa Kedokteran Indonesia, 9(3), 92-101.
Article Review


1. WHO -. WHO Coronavirus Disease (COVID-19) Dashboard [Internet]. 2020 [cited 2020 Jun 23]. Available from:
2. John Hopskins University. Mortality Analyses - Johns Hopkins Coronavirus Resource Center [Internet]. 2020 [cited 2020 Jun 23]. Available from:
3. 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 [Internet]. 2020 Mar 28 [cited 2020 Jun 23];395(10229):1054–62. Available from:
4. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China [Internet]. Vol. 46, Intensive Care Medicine. Springer; 2020 [cited 2020 Jun 23]. p. 846–8. Available from:
5. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. N Engl J Med [Internet]. 2020 May 21 [cited 2020 Jun 23];382(21):2012–22. Available from:
6. 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 [Internet]. 2020 Feb 15 [cited 2020 Jun 23];395(10223):497–506. Available from:
7. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med [Internet]. 2020 May 1 [cited 2020 Jun 23];8(5):475–81. Available from:
8. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and Outcomes of 21 Critically Ill Patients with COVID-19 in Washington State [Internet]. Vol. 323, JAMA - Journal of the American Medical Association. American Medical Association; 2020 [cited 2020 Jun 23]. p. 1612–4. Available from:
9. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected with SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA - J Am Med Assoc [Internet]. 2020 Apr 28 [cited 2020 Jun 23];323(16):1574–81. Available from:
10. Henry BM, De Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58(7):1021–8.
11. Ye Q, Wang B, Mao J. The pathogenesis and treatment of theCytokine Storm’in COVID-19. J Infect. 2020;80(6):607–13.
12. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant [Internet]. 2020/03/20. 2020 May;39(5):405–7. Available from:
13. 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 May 1;55(5):105954.
14. Wang Z, Han W. Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy. Biomark Res. 2018;6:4.
15. 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 May 19;117(20):10970–5.
16. Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? Vol. 18, Journal of translational medicine. 2020. p. 164.
17. Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? [Internet]. Vol. 395, The Lancet. Lancet Publishing Group; 2020 [cited 2020 Jun 23]. p. 1225–8. Available from: /pmc/articles/PMC7102589/?report=abstract
18. Klopfenstein T, Zayet S, Lohse A, Balblanc J-C, Badie J, Royer P-Y, et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Médecine Mal Infect [Internet]. 2020; Available from:
19. Morena V, Milazzo L, Oreni L, Bestetti G, Fossali T, Bassoli C, et al. Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy. Eur J Intern Med [Internet]. 2020/05/21. 2020 Jun;76:36–42. Available from:
20. Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, 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. Vol. 19, Autoimmunity Reviews. Elsevier B.V.; 2020. p. 102568.
21. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb;323(11):1061–9.
22. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun;307(23):2526–33.
23. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb;315(8):788–800.
24. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar;
25. Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust [Internet]. 2020 Jun 22 [cited 2020 Jun 28];213(2):n/a-n/a. Available from:
26. Younan P, Iampietro M, Nishida A, Ramanathan P, Santos RI, Dutta M, et al. Ebola virus binding to Tim-1 on T lymphocytes induces a cytokine storm. MBio. 2017;8(5).
27. 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):507–13.
28. Zhang Y, Geng X, Tan Y, Li Q, Xu C, Xu J, et al. New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. Biomed Pharmacother [Internet]. 2020;127:110195. Available from:
29. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv [Internet]. 2020 Jan 1;2020.02.06.20020974. Available from:
30. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16–32.
31. 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 Jan 24;395.
32. Saphire EO, Schendel SL, Gunn BM, Milligan JC, Alter G. Antibody-mediated protection against Ebola virus. Nat Immunol. 2018 Nov;19(11):1169–78.
33. Liu STH, Lin H-M, Baine I, Wajnberg A, Gumprecht JP, Rahman F, et al. Convalescent plasma treatment of severe COVID-19: A matched control study. medRxiv [Internet]. 2020 Jan 1;2020.05.20.20102236. Available from:
34. Joyner M, Wright RS, Fairweather D, Senefeld J, Bruno K, Klassen S, et al. Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients. medRxiv : the preprint server for health sciences. 2020.
35. Marovich M, Mascola JR, Cohen MS. Monoclonal Antibodies for Prevention and Treatment of COVID-19. JAMA [Internet]. 2020 Jun 15; Available from:
36. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Vol. 395, Lancet (London, England). 2020. p. 1033–4.
37. Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVID-19 or SARS-CoV-2): anti-inflammatory strategies. Vol. 34, Journal of biological regulators and homeostatic agents. Italy; 2020.
38. Roumier M, Paule R, Groh M, Valle A, Ackermann F. Interleukin-6 blockade for severe COVID-19. medRxiv [Internet]. 2020 Jan 1;2020.04.20.20061861. Available from:
39. Geng Z, Yu Y, Hu S, Dong L, Ye C. Tocilizumab and the risk of respiratory adverse events in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomised controlled trials. Clin Exp Rheumatol. 2019;37(2):318–23.
40. Scott LJ. Tocilizumab: A Review in Rheumatoid Arthritis. Drugs [Internet]. 2017 Nov;77(17):1865–79. Available from:
41. Alten R. Tocilizumab: a novel humanized anti-interleukin 6 receptor antibody for the treatment of patients with rheumatoid arthritis. Ther Adv Musculoskelet Dis [Internet]. 2011 Jun;3(3):133–49. Available from:
42. Schiff MH, Kremer JM, Jahreis A, Vernon E, Isaacs JD, van Vollenhoven RF. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011;13(5):R141.
43. Cantini F, Nannini C, Niccoli L, Petrone L, Ippolito G, Goletti D. Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics. Mediators Inflamm [Internet]. 2017/06/01. 2017;2017:8909834. Available from:
44. Wang S-X, Wang Y, Lu Y-B, Li J-Y, Song Y-J, Nyamgerelt M, et al. Diagnosis and treatment of novel coronavirus pneumonia based on the theory of traditional Chinese medicine. J Integr Med [Internet]. 2020 Apr 15;S2095-4964(20)30037-6. Available from:
45. Lombardy Section Italian Society Infectious And Tropical Diseases -. Vademecum for the treatment of people with COVID-19. Edition 2.0, 13 March 2020. Le Infez Med. 2020;28(2):143–52.