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Reviews on Recent Clinical Trials


ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

Review Article

Tocilizumab in SARS-CoV-2 Patients with the Syndrome of Cytokine Storm: A Narrative Review

Author(s): Shanmugaraj Kulanthaivel*, Vitalii B. Kaliberdenko, Keerthanaa Balasundaram, Michael V. Shterenshis, Emidio Scarpellini and Ludovico Abenavoli

Volume 16, Issue 2, 2021

Published on: 17 September, 2020

Page: [138 - 145] Pages: 8

DOI: 10.2174/1574887115666200917110954

Price: $65


Introduction: Corona virus is a group of viruses that cause diseases in mammals and birds. In humans, these families of viruses can cause respiratory infections from a mild form to fatal. It is preferably called coronavirus. Formally, it is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV) and this disease is called coronavirus disease 2019 (COVID-19). SARS-CoV-2 is infectious in humans and the world health organization has announced COVID-19 as pandemic disease. Tocilizumab is a biological agent that inhibits the cytokine, interleukin 6 (IL-6 inhibitor). As SARS-CoV-2 infection leads to the development of cytokine storm syndrome, the drug, tocilizumab, seems to have a positive effect on patients with COVID-19.

Aim: To analyze and review the possible effects and efficacy of the tocilizumab (monoclonal antibody against IL-6 receptors) in SARS-CoV-2 patients.

Materials and Methods: A search was carried out for all recent review articles, which were used to study the SARS-CoV-2 disease and their characteristics. Furthermore, we have analyzed the most recent research articles on monoclonal antibody against IL-6 receptors (tocilizumab) and their possible clinical effects in COVID-19 and its’ clinical trials.

Results: COVID-19 is a disease caused by SARS-CoV-2 infection. It is a life threatening condition, which can give rise to fatal outcomes if left untreated. However, there are no approved treatments for COVID-19 globally. Furthermore, we can conclude that SARS-CoV-2 is associated with the worsening of lung conditions, characterized by interstitial pneumonia with acute respiratory distress syndrome as a result of cytokine storm syndrome. According to available research data, tocilizumab, a recombinant humanized anti-human monoclonal antibody of IgG1τ (gamma 1, kappa), can improve patient’s condition from cytokine storm syndrome by inhibiting the IL-6 (Interleukin 6) receptors.

Conclusion: The rational use of the tocilizumab in severe and critically ill COVID-19 patients can prevent the development of irreversible lung injury and death of the patient. Three retrospective studies of Xiaoling Xu et al., Pan luo et al., and Paola Tonaiti et al. have shown the efficacy of tocilizumab in severe and critically ill COVID-19 patients. However, we need more randomized research studies with a significant number of patients which can confirm the promising results on tocilizumab treatment in COVID-19 patients. Moreover, ongoing clinical trails such as TOSCA, COVACTA results have not been published yet which are expected to give better and more significant results on tocilizumab’s effectiveness and safety.

Keywords: SARS-CoV-2, tocilizumab, Covid-19, interleukin 6 (IL-6), cytokine release syndrome, cytokine storm, acute respiratory distress syndrome, interstitial pneumonia.

Graphical Abstract
Gorbalenya AE, Baker SC, Baric RS, et al. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020; 5(4): 536-44.
[] [PMID: 32123347]
World Health Organization. Surveillance case definitions for human infection with novel coronavirus (nCoV): interim guidance v1 2020.
Surveillance case definitions for human infection with novel coronavirus (nCoV): interim guidance v1 World Health Organization 2019.
Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395(10223): 514-23.
[] [PMID: 31986261]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[] [PMID: 32015507]
Perlman S. Another Decade, Another Coronavirus. N Engl J Med 2020; 382(8): 760-2.
[] [PMID: 31978944]
Benvenuto D, Giovanetti M, Ciccozzi A, Spoto S, Angeletti S, Ciccozzi M. The 2019-new coronavirus epidemic: Evidence for virus evolution. J Med Virol 2020; 92(4): 455-9.
[] [PMID: 31994738]
Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med 2020; 26(4): 450-2.
[] [PMID: 32284615]
Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 2020; 15(5): 700-4.
[] [PMID: 32114094]
Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks. Pathogens 2020; 9(3): 186.
[] [PMID: 32143502]
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39(5): 529-39.
[] [PMID: 28466096]
Gentile I, Abenavoli L. COVID-19: Perspectives on the Potential Novel Global Threat. Rev Recent Clin Trials 2020; 15(2): 84-6.
[] [PMID: 32116200]
Kaliberdenko V, Kulanthaivel S, Shterenshis M, et al. Creatinuria and dynamics of calcium metabolism in children in the phase of exacerbation of bronchial asthma. Curr Respir Med Rev 2020; 16(1): 28-33.
Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet 2020; 395(10224): e35-6.
[] [PMID: 32035018]
Masters PS. The molecular biology of coronaviruses. Adv Virus Res 2006; 66: 193-292.
[] [PMID: 16877062]
Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet 2015; 386(9997): 995-1007.
[] [PMID: 26049252]
Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367(19): 1814-20.
[] [PMID: 23075143]
Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 2009; 7(6): 439-50.
[] [PMID: 19430490]
Drosten C, Günther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003; 348(20): 1967-76.
[] [PMID: 12690091]
Ksiazek TG, Erdman D, Goldsmith CS, et al. SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348(20): 1953-66.
[] [PMID: 12690092]
Peiris JSM, Lai ST, Poon LL, et al. SARS study group. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003; 361(9366): 1319-25.
[] [PMID: 12711465]
Snijder EJ, Bredenbeek PJ, Dobbe JC, et al. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 2003; 331(5): 991-1004.
[] [PMID: 12927536]
van Boheemen S, de Graaf M, Lauber C, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 2012; 3(6): e00473-12.
[] [PMID: 23170002]
Siddell SG, Walker PJ, Lefkowitz EJ, et al. Additional changes to taxonomy ratified in a special vote by the International Committee on Taxonomy of Viruses (October 2018). Arch Virol 2019; 164(3): 943-6.
[] [PMID: 30663020]
Ziebuhr J, et al. 013S. A.v1. Reorganization of the family Coronaviridae into two families, Coronaviridae (including the current subfamily Coronavirinae and the new subfamily Letovirinae) and the new family Tobaniviridae (accommodating the current subfamily Torovirinae and three other subfamilies), revision of the genus rank structure and introduction of a new subgenus rank ICTV 2017.
Ziebuhr J, et al. Proposal 2019.021S.Ac.v1. Create ten new species and a new genus in the subfamily Orthocoronavirinae of the family Coronaviridae and five new species and a new genus in the subfamily Serpentovirinae of the family Tobaniviridae ICTV 2019.
de Groot RJ, et al. Virus Taxonomy, Ninth Report of the International Committee on Taxonomy of Viruses. Elsevier Academic Press 2012; pp. 806-28.
Lauber C, Gorbalenya AE. Toward genetics-based virus taxonomy: comparative analysis of a genetics-based classification and the taxonomy of picornaviruses. J Virol 2012; 86(7): 3905-15.
[] [PMID: 22278238]
Van Regenmortel MHV. The species problem in virology. Adv Virus Res 2018; 100: 1-18.
[] [PMID: 29551132]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[] [PMID: 31986264]
Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl) 2020; 133(9): 1025-31.
[] [PMID: 32044814]
Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020; 382(13): 1199-207.
[] [PMID: 31995857]
Liu Y, Gayle A A, Wilder-Smith A, Rocklov J. The reproductive number of COVID-19 is higher compared to SARS coronavirus J Travel Med 2020.
Tang B, Wang X, Li Q, et al. Estimation of the transmission risk of the 2019-nCoV and its implication for public health interventions. J Clin Med 2020; 9(2): 462.
[] [PMID: 32046137]
Abenavoli L, Cinaglia P, Luzza F, Gentile I, Boccuto L. Epidemiology of Coronavirus Disease Outbreak: The Italian Trends. Rev Recent Clin Trials 2020; 15(2): 87-92.
[] [PMID: 32264813]
Novel Coronavirus (2019-nCoV) Situation Report – 22, World Health Organization 2020.
Coronavirus disease (COVID-19) outbreak, World Health Organization 2020.
Harrison C. Coronavirus puts drug repurposing on the fast track. Nat Biotechnol 2020; 38(4): 379-81.
[] [PMID: 32205870]
Wang Y,, Zhang D,, Du G,, et al. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial Lancet 2020; 395(10236): 1569-78.
Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020; 382(19): 1787-99.
[] [PMID: 32187464]
Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14(1): 72-3.
[] [PMID: 32074550]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[] [PMID: 32020029]
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56(1)105949
[] [PMID: 32205204]
Chen J, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of Zhejiang University 2020; 49(1) [Med Sci
[] [PMID: 32391667]
Coronavirus Disease 2019 (COVID-19) Situation Report 33. World Health Organization 2020.
WHO Director-General's opening remarks at the media briefing on COVID19 2020.
Coronavirus Disease 2019 (COVID-19) Situation Report 114. World Health Organization 2020.
Zhu N, Zhang D, Wang W, et al. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
[] [PMID: 31978945]
The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. 2020.
Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet 2020; 395(10223): e30-1.
[] [PMID: 32032529]
Kaliberdenko VB, Kuznetsov ES, Shanmugaraj K, et al. Development of cardiovascular complications in polycythemia vera patients influenced by increased blood viscosity. Indian Journal of Public Health Research and Development 2019; 10(9): 719-23.
Le RQ, Li L, Yuan W, et al. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. Oncologist 2018; 23(8): 943-7.
[] [PMID: 29622697]
Icon CK, 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): 813-22.
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. PNAS. 117(20): 10970-5.
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): 814-8.
[] [PMID: 32253759]
Toniati Paola, Pivab Simone, Cattalini Marco, 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 2020.

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