Generic placeholder image

Recent Patents on Anti-Infective Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-891X
ISSN (Online): 2212-4071

Mini-Review Article

The Role of Tocilizumab in Cytokine Storm and Improving Outcomes in COVID-19

Author(s): Afroze Ali*, Milad H. Kamjani and Marc M. Kesselman

Volume 15, Issue 2, 2020

Page: [104 - 112] Pages: 9

DOI: 10.2174/1574891X15666200922155712

open access plus

Abstract

To date, severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has infected millions of individuals worldwide. This virus causes coronavirus disease 2019 (COVID-19) and has led to numerous deaths worldwide. A large percentage of infected patients present asymptomatically, augmenting the spread of the virus. Symptomatic COVID-19 commonly causes mild to severe respiratory disease and fever, but some individuals experience serious complications resulting in death. Immune compromised, high risk, and elderly individuals are at an increased risk of more severe consequences of the illness such as respiratory failure, organ dysfunction, and shock. Cytokine storm (also known as cytokine release syndrome (CRS)), a systemic inflammatory response that can be triggered by an infection, has been associated with the symptom progression of COVID-19. This review evaluates several published studies that have implemented tocilizumab (TCZ), an IL-6 receptor antibody (US20120253016A1), in COVID-19 treatment. Outcomes and biomarkers of patients treated with TCZ are compared to patients treated with standard of care regimens. Interleukin-6 (IL-6), a prominent inflammatory cytokine involved in CRS in various inflammatory conditions, may have a vital role in the underlying mechanism involved in debilitating SARS-CoV-2 infections and could serve as a viable treatment target. Studies suggest that TCZ may aid in the recovery of patients with COVID-19 and reduce mortality.

Keywords: Tocilizumab, COVID-19, SARS-CoV-2, cytokine storm, cytokine release syndrome, IL-6.

Next »
Graphical Abstract

[1]
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents 2020; 55(3): 105924.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105924] [PMID: 32081636]
[2]
Du Toit A. Outbreak of a novel coronavirus. Nat Rev Microbiol 2020; 18(3): 123.
[http://dx.doi.org/10.1038/s41579-020-0332-0] [PMID: 31988490]
[3]
Cucinotta D, Vanelli M. WHO declares covid-19 a pandemic. Acta Biomed 2020; 91(1): 157-60.
[PMID: 32191675]
[4]
Pericàs JM, Hernandez-Meneses M, Sheahan TP, Quintana E, Ambrosioni J, Sandoval E, et al. Hospital clínic cardiovascular infections study group. COVID-19: from epidemiology to treatment. Eur Heart J 2020; 41(22): 2092-112.
[http://dx.doi.org/10.1093/eurheartj/ehaa462] [PMID: 32511724]
[5]
Martin JH, Bowden NA. Drug repurposing in the era of COVID-19: a call for leadership and government investment. Med J Aust 2020; 212(10): 450-2.
[http://dx.doi.org/10.5694/mja2.50603] [PMID: 32372435]
[6]
Jayaweera M, Perera H, Gunawardana B, Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res 2020; 188: 109819.
[http://dx.doi.org/10.1016/j.envres.2020.109819] [PMID: 32569870]
[7]
Abd El-Aziz TM, Stockand JD. Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status. Infect Genet Evol 2020; 83: 104327.
[http://dx.doi.org/10.1016/j.meegid.2020.104327] [PMID: 32320825]
[8]
Cooper KW, Brann DH, Farruggia MC, Bhutani S, Pellegrino R, Tsukahara T, et al. Covid-19 and the chemical senses: supporting players take center stage. Neuron 2020; 107(2): 219-33.
[http://dx.doi.org/10.1016/j.neuron.2020.06.032] [PMID: 32640192]
[9]
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382(18): 1708-20.
[http://dx.doi.org/10.1056/NEJMoa2002032] [PMID: 32109013]
[10]
Li X, Ma X. Acute respiratory failure in COVID-19: is it “typical” ARDS? Crit Care 2020; 24(1): 198.
[http://dx.doi.org/10.1186/s13054-020-02911-9] [PMID: 32375845]
[11]
Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated troponin in patients with coronavirus disease 2019: possible mechanisms. J Card Fail 2020; 26(6): 470-5.
[http://dx.doi.org/10.1016/j.cardfail.2020.04.009] [PMID: 32315733]
[12]
Fried JA, Ramasubbu K, Bhatt R, Topkara VK, Clerkin KJ, Horn E, et al. The variety of cardiovascular presentations of covid-19. Circulation 2020; 141(23): 1930-6.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047164] [PMID: 32243205]
[13]
Hess DC, Eldahshan W, Rutkowski E. Covid-19-related stroke. Transl Stroke Res 2020; 11(3): 322-5.
[http://dx.doi.org/10.1007/s12975-020-00818-9] [PMID: 32378030]
[14]
Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res 2020; 116(10): 1666-87.
[http://dx.doi.org/10.1093/cvr/cvaa106] [PMID: 32352535]
[15]
Muscogiuri G, Pugliese G, Barrea L, Savastano S, Colao A. Commentary: obesity: the “Achilles heel” for COVID-19? Metabolism 2020; 108: 154251.
[http://dx.doi.org/10.1016/j.metabol.2020.154251] [PMID: 32353356]
[16]
Xie M, Chen Q. Insight into 2019 novel coronavirus-an updated interim review and lessons from SARS-CoV and MERS-CoV. Int J Infect Dis 2020; 94: 119-24.
[http://dx.doi.org/10.1016/j.ijid.2020.03.071] [PMID: 32247050]
[17]
Yan Y, Shin WI, Pang YX, Meng Y, Lai J, You C, et al. The first 75 days of novel coronavirus (sars-cov-2) outbreak: recent advances, prevention, and treatment. Int J Environ Res Public Health 2020; 17(7): 2323.
[http://dx.doi.org/10.3390/ijerph17072323] [PMID: 32235575]
[18]
Sun X, Wang T, Cai D, Hu Z, Liao H, Zhi L, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. cytokine Growth Factor Rev 2020; 53(38): 42.
[http://dx.doi.org/10.1016/j.cytogfr.2020.04.002] [PMID: 32360420]
[19]
Jamilloux Y, Henry T, Belot A, Viel S, Fauter M, El Jammal T, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev 2020; 19(7): 102567.
[http://dx.doi.org/10.1016/j.autrev.2020.102567] [PMID: 32376392]
[20]
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(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[21]
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.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105954] [PMID: 32234467]
[22]
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368(6490): 473-4.
[http://dx.doi.org/10.1126/science.abb8925] [PMID: 32303591]
[23]
Lai CC, Ko WC, Lee PI, Jean SS, Hsueh PR. Extra-respiratory manifestations of COVID-19. Int J Antimicrob Agents 2020; 56(2): 106024.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.106024] [PMID: 32450197]
[24]
Baran P, Hansen S, Waetzig GH, Akbarzadeh M, Lamertz L, Huber HJ, et al. The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling. J Biol Chem 2018; 293(18): 6762-75.
[http://dx.doi.org/10.1074/jbc.RA117.001163] [PMID: 29559558]
[25]
Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nat Rev Rheumatol 2017; 13(7): 399-409.
[http://dx.doi.org/10.1038/nrrheum.2017.83] [PMID: 28615731]
[26]
González-Gay MA, Mayo J, Castañeda S, Cifrián JM, Hernández-Rodríguez J. Tocilizumab: from the rheumatology practice to the fight against COVID-19, a virus infection with multiple faces. Expert Opin Biol Ther 2020; 20(7): 717-23.
[http://dx.doi.org/10.1080/14712598.2020.1770222] [PMID: 32406282]
[27]
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. Autoimmun Rev 2020; 19(7): 102568.
[http://dx.doi.org/10.1016/j.autrev.2020.102568] [PMID: 32376398]
[28]
Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med 2020; 76: 31-5.
[http://dx.doi.org/10.1016/j.ejim.2020.05.009] [PMID: 32405160]
[29]
Sciascia S, Aprà F, Baffa A, Baldovino S, Boaro D, Boero R, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol 2020; 38(3): 529-32.
[PMID: 32359035]
[30]
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 USA 2020; 117(20): 10970-5.
[http://dx.doi.org/10.1073/pnas.2005615117] [PMID: 32350134]
[31]
Somers EC, Eschenauer GA, Troost JP, Golob JL, Gandhi TN, Wang L, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis 2020; ciaa954.
[http://dx.doi.org/10.1093/cid/ciaa954] [PMID: 32651997]
[32]
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 Rheumatology 2020; 2(8): e474-84.
[33]
Coyle J, Igbinomwanhia E, Sanchez-Nadales A, Danciu S, Chu C, Shah N. A recovered case of covid-19 myocarditis and ARDS treated with corticosteroids, tocilizumab, and experimental AT-001. JACC Case Rep 2020; 2(9): 1331-6.
[http://dx.doi.org/10.1016/j.jaccas.2020.04.025]
[34]
Bjornsson AH, Olafsdottir T, Thormar KM, Kristjansson M, Thorisdottir AS, Ludviksson BR, et al. First case of COVID-19 treated with tocilizumab in Iceland. Laeknabladid 2020; 106(5): 247-50.
[PMID: 32367812]
[35]
Zhang X, Song K, Tong F, Fei M, Guo H, Lu Z, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv 2020; 4(7): 1307-10.
[http://dx.doi.org/10.1182/bloodadvances.2020001907] [PMID: 32243501]
[36]
Lambden S, Laterre PF, Levy MM, Francois B. The SOFA score-development, utility and challenges of accurate assessment in clinical trials. Crit Care 2019; 23(1): 374.
[http://dx.doi.org/10.1186/s13054-019-2663-7] [PMID: 31775846]
[37]
Klopfenstein T, Zayet S, Lohse A, Balblanc JC, Badie J, Royer PY, et al. HNF Hospital Tocilizumab multidisciplinary team. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Med Mal Infect 2020; 50(5): 397-400.
[http://dx.doi.org/10.1016/j.medmal.2020.05.001] [PMID: 32387320]
[38]
Colaneri M, Bogliolo L, Valsecchi P, Sacchi P, Zuccaro V, Brandolino F, et al. The Covid Irccs San Matteo Pavia Task Force. Tocilizumab for treatment of severe covid-19 patients: Preliminary results from smatteo covid19 registry (smacore). Microorganisms 2020; 8(5): E695.
[http://dx.doi.org/10.3390/microorganisms8050695] [PMID: 32397399]
[39]
Igawa T, Ishii S, Maeda A, Sakurai M, Kojima T, Tachibana T, Shiraiwa H, Tsunoda H, Higuchi Y. Antibody molecules that bind to il-6 receptor. US20120253016A1 (2012).
[40]
Graham LD. Treatment methods for rheumatoid arthritis. US9387246B2 (2016).
[41]
June CH, Station M, Levine BL, Kalos MD, Grupp S. Toxicity management for anti-tumor activity of cars. US10603378B2 (2020).
[42]
Bao M, Harari OA, Jahreis AM, Schmidt JF, Zhang X. Subcutaneously administered anti-il-6 receptor antibody. US20120301460A1 (2012).
[43]
Atal S, Fatima Z. Il-6 inhibitors in the treatment of serious covid-19: a promising therapy? Pharmaceut Med 2020; 34(4): 223-31.
[http://dx.doi.org/10.1007/s40290-020-00342-z] [PMID: 32535732]
[44]
Mihai C, Dobrota R. Schröder MMihai C, Dobrota R, Schröder M, Garaiman A, Jordan S, Becker MO. Ann Rheum Dis 2020; 79(5): 668-9.
[http://dx.doi.org/10.1136/annrheumdis-2020-217442] [PMID: 32241792]
[45]
Wu R, Wang L, Kuo HC, Shannar A, Peter R, Chou PJ, et al. An update on current therapeutic drugs treating covid-19. Curr Pharmacol Rep 2020; 2020: 1-15.
[PMID: 32395418]
[46]
Iannaccone G, Scacciavillani R, Del Buono MG, Camilli M, Ronco C, Lavie CJ, et al. Weathering the cytokine storm in covid-19: therapeutic implications. Cardiorenal Med 2020; 10(5): 277-87.
[http://dx.doi.org/10.1159/000509483] [PMID: 32599589]

© 2024 Bentham Science Publishers | Privacy Policy