Does tocilizumab have an effect on the clinical outcomes in COVID-19 patients? A meta-analysis of randomized control trials

DOI record: { "DOI": "10.1186/s40545-023-00662-w", "ISSN": [ "2052-3211" ], "URL": "http://dx.doi.org/10.1186/s40545-023-00662-w", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>This meta-analysis was conducted to investigate the impact of tocilizumab on clinical outcomes associated with COVID-19.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>A comprehensive search was conducted across Scopus, PubMed (Medline), Cochrane Library, EMBASE (Elsevier), ClinicalTrials.gov, and Web of Sciences to identify pertinent studies published until May 2022. The primary search terms included \"tocilizumab\" and \"COVID-19\". Following the formulation of the search strategy, all identified studies were screened, and the data extraction process was initiated. Subsequently, the Cochrane risk of bias checklist was employed to evaluate the risk of bias. The effects of tocilizumab were assessed utilizing the pooled risk ratio (RR) and the fixed effect model in STATA (version 17).</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>In this meta-analysis, we analyzed 17 clinical trial studies to assess the impact of tocilizumab on mortality in patients with COVID-19. The pooled risk ratio (RR) for mortality was 0.93 (RR: 0.93; 95% CI: 0.86, 1.00; <jats:italic>I</jats:italic><jats:sup>2</jats:sup>: 72.39%; <jats:italic>P</jats:italic> value: 0.001). The findings indicated that tocilizumab use was associated with a 4% increase in ICU hospitalization (RR: 1.04; 95% CI: 0.90, 1.20; <jats:italic>I</jats:italic><jats:sup>2</jats:sup>: 0.00%; <jats:italic>P</jats:italic> value: 0.65). Additionally, tocilizumab administration was linked to a 2% reduction in the requirement for a ventilator (RR: 0.98; 95% CI: 0.90, 1.08; <jats:italic>I</jats:italic><jats:sup>2</jats:sup>: 26.87%; <jats:italic>P</jats:italic> value: 0.16).</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>The administration of tocilizumab during the COVID-19 pandemic, prescribed to patients with the virus, exerted a noteworthy impact on reducing outcomes associated with COVID-19.</jats:p>\n </jats:sec>", "alternative-id": [ "662" ], "article-number": "151", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "19 January 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "14 November 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "20 November 2023" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "Not applicable. This is a systematic literature review." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "The authors declare that they have no competing interests." } ], "author": [ { "affiliation": [], "family": "Ghaempanah", "given": "Faezeh", "sequence": "first" }, { "affiliation": [], "family": "Nikouei", "given": "Maziar", "sequence": "additional" }, { "affiliation": [], "family": "Cheraghi", "given": "Mojtaba", "sequence": "additional" }, { "affiliation": [], "family": "Jahangiri", "given": "Arman", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-2936-5930", "affiliation": [], "authenticated-orcid": false, "family": "Moradi", "given": "Yousef", "sequence": "additional" } ], "container-title": "Journal of Pharmaceutical Policy and Practice", "container-title-short": "J of Pharm Policy and Pract", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T10:05:44Z", "timestamp": 1700474744000 }, "deposited": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T10:54:12Z", "timestamp": 1700477652000 }, "indexed": { "date-parts": [ [ 2023, 11, 21 ] ], "date-time": "2023-11-21T00:11:15Z", "timestamp": 1700525475721 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2023, 11, 20 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2023, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T00:00:00Z", "timestamp": 1700438400000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 11, 20 ] ], "date-time": "2023-11-20T00:00:00Z", "timestamp": 1700438400000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s40545-023-00662-w.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s40545-023-00662-w/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s40545-023-00662-w.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2023, 11, 20 ] ] }, "published-online": { "date-parts": [ [ 2023, 11, 20 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1016/j.chom.2020.02.001", "author": "A Wu", "doi-asserted-by": "publisher", "first-page": "325", "issue": "3", "journal-title": "Cell Host Microbe", "key": "662_CR1", "unstructured": "Wu A, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020;27(3):325–8.", "volume": "27", "year": "2020" }, { "key": "662_CR2", "unstructured": "Organization, W.H., World Health Organization Coronavirus Disease (COVID-19): Weekly Epidemiological Update. 2021." }, { "DOI": "10.1001/jama.2020.1097", "author": "AL Phelan", "doi-asserted-by": "publisher", "first-page": "709", "issue": "8", "journal-title": "JAMA", "key": "662_CR3", "unstructured": "Phelan AL, Katz R, Gostin LO. The novel coronavirus originating in Wuhan, China: challenges for global health governance. JAMA. 2020;323(8):709–10.", "volume": "323", "year": "2020" }, { "DOI": "10.1016/j.ijantimicag.2020.105954", "author": "C Zhang", "doi-asserted-by": "publisher", "issue": "5", "journal-title": "Int J Antimicrob Agents", "key": "662_CR4", "unstructured": "Zhang C, et al. 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.", "volume": "55", "year": "2020" }, { "DOI": "10.1016/j.cytogfr.2020.05.003", "author": "F Coperchini", "doi-asserted-by": "publisher", "first-page": "25", "journal-title": "Cytokine Growth Factor Rev", "key": "662_CR5", "unstructured": "Coperchini F, et al. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25–32.", "volume": "53", "year": "2020" }, { "DOI": "10.1101/cshperspect.a016295", "author": "T Tanaka", "doi-asserted-by": "publisher", "issue": "10", "journal-title": "Cold Spring Harb Perspect Biol", "key": "662_CR6", "unstructured": "Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10): a016295.", "volume": "6", "year": "2014" }, { "DOI": "10.1016/j.jaci.2020.07.009", "doi-asserted-by": "crossref", "key": "662_CR7", "unstructured": "Laguna-Goya, R., et al., IL-6–based mortality risk model for hospitalized patients with COVID-19. Journal of Allergy and Clinical Immunology, 2020. 146(4): p. 799–807. e9." }, { "DOI": "10.3899/jrheum.100717", "author": "JA Singh", "doi-asserted-by": "publisher", "first-page": "10", "issue": "1", "journal-title": "J Rheumatol", "key": "662_CR8", "unstructured": "Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2011;38(1):10–20.", "volume": "38", "year": "2011" }, { "DOI": "10.1007/s40744-018-0102-x", "author": "A Rubbert-Roth", "doi-asserted-by": "publisher", "first-page": "21", "issue": "1", "journal-title": "Rheumatology and therapy", "key": "662_CR9", "unstructured": "Rubbert-Roth A, et al. A review of recent advances using tocilizumab in the treatment of rheumatic diseases. Rheumatology and therapy. 2018;5(1):21–42.", "volume": "5", "year": "2018" }, { "author": "DW Lee", "first-page": "188", "issue": "2", "journal-title": "Blood, The Journal of the American Society of Hematology", "key": "662_CR10", "unstructured": "Lee DW, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood, The Journal of the American Society of Hematology. 2014;124(2):188–95.", "volume": "124", "year": "2014" }, { "DOI": "10.1016/j.cmi.2021.04.019", "author": "IM Tleyjeh", "doi-asserted-by": "publisher", "first-page": "1076", "issue": "8", "journal-title": "Clin Microbiol Infect", "key": "662_CR11", "unstructured": "Tleyjeh IM, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update. Clin Microbiol Infect. 2021;27(8):1076–82.", "volume": "27", "year": "2021" }, { "DOI": "10.1016/S2665-9913(20)30173-9", "author": "G Guaraldi", "doi-asserted-by": "publisher", "first-page": "e474", "issue": "8", "journal-title": "The Lancet Rheumatology", "key": "662_CR12", "unstructured": "Guaraldi G, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. The Lancet Rheumatology. 2020;2(8):e474–84.", "volume": "2", "year": "2020" }, { "DOI": "10.1080/14740338.2021.1946513", "author": "J Charan", "doi-asserted-by": "publisher", "first-page": "1125", "issue": "9", "journal-title": "Expert Opin Drug Saf", "key": "662_CR13", "unstructured": "Charan J, et al. Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database. Expert Opin Drug Saf. 2021;20(9):1125–36.", "volume": "20", "year": "2021" }, { "DOI": "10.1016/j.cmi.2020.10.036", "author": "IM Tleyjeh", "doi-asserted-by": "publisher", "first-page": "215", "issue": "2", "journal-title": "Clin Microbiol Infect", "key": "662_CR14", "unstructured": "Tleyjeh IM, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect. 2021;27(2):215–27.", "volume": "27", "year": "2021" }, { "DOI": "10.1002/jmv.26509", "author": "M Aziz", "doi-asserted-by": "publisher", "first-page": "1620", "issue": "3", "journal-title": "J Med Virol", "key": "662_CR15", "unstructured": "Aziz M, et al. Efficacy of tocilizumab in COVID-19: a systematic review and meta-analysis. J Med Virol. 2021;93(3):1620–30.", "volume": "93", "year": "2021" }, { "DOI": "10.1371/journal.pone.0269368", "author": "A Piscoya", "doi-asserted-by": "publisher", "issue": "6", "journal-title": "PLoS ONE", "key": "662_CR16", "unstructured": "Piscoya A, et al. Efficacy and harms of tocilizumab for the treatment of COVID-19 patients: A systematic review and meta-analysis. PLoS ONE. 2022;17(6): e0269368.", "volume": "17", "year": "2022" }, { "DOI": "10.1136/annrheumdis-2020-218122", "author": "E Della-Torre", "doi-asserted-by": "publisher", "first-page": "1277", "issue": "10", "journal-title": "Ann Rheum Dis", "key": "662_CR17", "unstructured": "Della-Torre E, et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study. Ann Rheum Dis. 2020;79(10):1277–85.", "volume": "79", "year": "2020" }, { "DOI": "10.1186/s13643-021-01626-4", "author": "MJ Page", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Syst Rev", "key": "662_CR18", "unstructured": "Page MJ, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10(1):1–11.", "volume": "10", "year": "2021" }, { "DOI": "10.1186/1471-2288-1-2", "doi-asserted-by": "crossref", "key": "662_CR19", "unstructured": "Moher, D., et al., The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. 2001, Elsevier." }, { "DOI": "10.1186/1741-7015-8-18", "author": "KF Schulz", "doi-asserted-by": "publisher", "first-page": "18", "issue": "1", "journal-title": "BMC Med", "key": "662_CR20", "unstructured": "Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8(1):18.", "volume": "8", "year": "2010" }, { "DOI": "10.1136/bmj.d5928", "author": "JP Higgins", "doi-asserted-by": "publisher", "journal-title": "BMJ", "key": "662_CR21", "unstructured": "Higgins JP, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343: d5928.", "volume": "343", "year": "2011" }, { "key": "662_CR22", "unstructured": "Veiga, V.C., et al., Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. bmj, 2021. 372." }, { "key": "662_CR23", "unstructured": "Rosas, I.O., et al., Tocilizumab in hospitalized patients with COVID-19 pneumonia. MedRxiv, 2020." }, { "key": "662_CR24", "unstructured": "Wang, D., et al., Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial. Front Med 2021.[Epub ahead of print]. PUBMED." }, { "DOI": "10.1016/j.ejim.2020.05.009", "author": "R Capra", "doi-asserted-by": "publisher", "first-page": "31", "journal-title": "Eur J Intern Med", "key": "662_CR25", "unstructured": "Capra R, 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.", "volume": "76", "year": "2020" }, { "DOI": "10.1038/s41598-021-88086-x", "author": "A Rashad", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Sci Rep", "key": "662_CR26", "unstructured": "Rashad A, et al. Short term survival of critically ill COVID-19 Egyptian patients on assisted ventilation treated by either Dexamethasone or Tocilizumab. Sci Rep. 2021;11(1):1–7.", "volume": "11", "year": "2021" }, { "DOI": "10.1001/jamainternmed.2020.6820", "author": "O Hermine", "doi-asserted-by": "publisher", "first-page": "32", "issue": "1", "journal-title": "JAMA Intern Med", "key": "662_CR27", "unstructured": "Hermine O, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181(1):32–40.", "volume": "181", "year": "2021" }, { "DOI": "10.1016/S2213-2600(21)00081-3", "author": "AS Soin", "doi-asserted-by": "publisher", "first-page": "511", "issue": "5", "journal-title": "Lancet Respir Med", "key": "662_CR28", "unstructured": "Soin AS, et al. Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med. 2021;9(5):511–21.", "volume": "9", "year": "2021" }, { "DOI": "10.1186/s12967-020-02573-9", "doi-asserted-by": "crossref", "key": "662_CR29", "unstructured": "Perrone, F., et al., Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. Journal of translational medicine, 2020. 18(1): p. 1–11." }, { "key": "662_CR30", "unstructured": "Rocco, P.R., et al., Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial. European Respiratory Journal, 2021. 58(1)." }, { "DOI": "10.1016/j.jiph.2021.06.003", "author": "DM Hamed", "doi-asserted-by": "publisher", "first-page": "985", "issue": "8", "journal-title": "J Infect Public Health", "key": "662_CR31", "unstructured": "Hamed DM, et al. Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison. J Infect Public Health. 2021;14(8):985–9.", "volume": "14", "year": "2021" }, { "DOI": "10.1016/j.biopha.2020.110825", "author": "H Zhao", "doi-asserted-by": "publisher", "journal-title": "Biomed Pharmacother", "key": "662_CR32", "unstructured": "Zhao H, et al. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed Pharmacother. 2021;133: 110825.", "volume": "133", "year": "2021" }, { "DOI": "10.1002/cpt.2117", "author": "GW Strohbehn", "doi-asserted-by": "publisher", "first-page": "688", "issue": "3", "journal-title": "Clin Pharmacol Ther", "key": "662_CR33", "unstructured": "Strohbehn GW, et al. COVIDOSE: a phase II clinical trial of low-dose tocilizumab in the treatment of noncritical COVID-19 pneumonia. Clin Pharmacol Ther. 2021;109(3):688–96.", "volume": "109", "year": "2021" }, { "DOI": "10.1111/bcp.14466", "doi-asserted-by": "crossref", "key": "662_CR34", "unstructured": "Baker, E.H., et al., Insights from compassionate use of tocilizumab for COVID‐19 to inform appropriate design of randomised controlled trials. British Journal of Clinical Pharmacology, 2021." }, { "key": "662_CR35", "unstructured": "McAuley, D. and R.-C.W. Committee, Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. New England Journal of Medicine, 2021." }, { "DOI": "10.1016/j.intimp.2020.106869", "author": "F Dastan", "doi-asserted-by": "publisher", "journal-title": "Int Immunopharmacol", "key": "662_CR36", "unstructured": "Dastan F, et al. Promising effects of tocilizumab in COVID-19: a non-controlled, prospective clinical trial. Int Immunopharmacol. 2020;88: 106869.", "volume": "88", "year": "2020" }, { "DOI": "10.1111/joim.13231", "author": "G Pomponio", "doi-asserted-by": "publisher", "first-page": "738", "issue": "5", "journal-title": "J Intern Med", "key": "662_CR37", "unstructured": "Pomponio G, et al. Tocilizumab in COVID-19 interstitial pneumonia. J Intern Med. 2021;289(5):738–46.", "volume": "289", "year": "2021" }, { "key": "662_CR38", "unstructured": "Salama, C. and S.V. Mohan, Tocilizumab in patients hospitalized with Covid-19 pneumonia. Reply. The New England journal of medicine, 2021." }, { "DOI": "10.1002/jcph.1693", "author": "S Khiali", "doi-asserted-by": "publisher", "first-page": "1131", "issue": "9", "journal-title": "J Clin Pharmacol", "key": "662_CR39", "unstructured": "Khiali S, Khani E, Entezari-Maleki T. A comprehensive review of tocilizumab in COVID-19 acute respiratory distress syndrome. J Clin Pharmacol. 2020;60(9):1131–46.", "volume": "60", "year": "2020" }, { "DOI": "10.2165/00003495-200969050-00007", "author": "V Oldfield", "doi-asserted-by": "publisher", "first-page": "609", "issue": "5", "journal-title": "Drugs", "key": "662_CR40", "unstructured": "Oldfield V, Dhillon S, Plosker GL. Tocilizumab. Drugs. 2009;69(5):609–32.", "volume": "69", "year": "2009" }, { "DOI": "10.1016/j.autrev.2020.102568", "author": "P Toniati", "doi-asserted-by": "publisher", "issue": "7", "journal-title": "Autoimmun Rev", "key": "662_CR41", "unstructured": "Toniati P, 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.", "volume": "19", "year": "2020" }, { "DOI": "10.1111/sji.12998", "author": "AU Anka", "doi-asserted-by": "publisher", "issue": "4", "journal-title": "Scand J Immunol", "key": "662_CR42", "unstructured": "Anka AU, et al. Coronavirus disease 2019 (COVID-19): An overview of the immunopathology, serological diagnosis and management. Scand J Immunol. 2021;93(4): e12998.", "volume": "93", "year": "2021" }, { "DOI": "10.1002/jmv.25685", "author": "G Li", "doi-asserted-by": "publisher", "first-page": "424", "issue": "4", "journal-title": "J Med Virol", "key": "662_CR43", "unstructured": "Li G, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424–32.", "volume": "92", "year": "2020" }, { "DOI": "10.1038/nri3581", "author": "LB Ivashkiv", "doi-asserted-by": "publisher", "first-page": "36", "issue": "1", "journal-title": "Nat Rev Immunol", "key": "662_CR44", "unstructured": "Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14(1):36–49.", "volume": "14", "year": "2014" }, { "DOI": "10.1016/j.intimp.2020.107364", "author": "LM Khosroshahi", "doi-asserted-by": "publisher", "journal-title": "Int Immunopharmacol", "key": "662_CR45", "unstructured": "Khosroshahi LM, et al. Immunology, immunopathogenesis and immunotherapeutics of COVID-19; an overview. Int Immunopharmacol. 2021;93: 107364.", "volume": "93", "year": "2021" }, { "DOI": "10.1002/jmv.26232", "author": "B Hu", "doi-asserted-by": "publisher", "first-page": "250", "issue": "1", "journal-title": "J Med Virol", "key": "662_CR46", "unstructured": "Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250–6.", "volume": "93", "year": "2021" }, { "DOI": "10.1002/rmv.2141", "author": "EA Coomes", "doi-asserted-by": "publisher", "first-page": "1", "issue": "6", "journal-title": "Rev Med Virol", "key": "662_CR47", "unstructured": "Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: a systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9.", "volume": "30", "year": "2020" }, { "key": "662_CR48", "unstructured": "Gaestel, M., A.R. Nebreda, and M.B. Yaffe, Cytokine Storm. 2021." }, { "DOI": "10.1111/imm.13223", "author": "M Tan", "doi-asserted-by": "publisher", "first-page": "261", "issue": "3", "journal-title": "China Immunology", "key": "662_CR49", "unstructured": "Tan M, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou. China Immunology. 2020;160(3):261–8.", "volume": "160", "year": "2020" }, { "DOI": "10.1186/s40425-018-0343-9", "author": "A Shimabukuro-Vornhagen", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "J Immunother Cancer", "key": "662_CR50", "unstructured": "Shimabukuro-Vornhagen A, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):1–14.", "volume": "6", "year": "2018" }, { "DOI": "10.1056/NEJMra1608077", "author": "BT Thompson", "doi-asserted-by": "publisher", "first-page": "562", "issue": "6", "journal-title": "N Engl J Med", "key": "662_CR51", "unstructured": "Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;377(6):562–72.", "volume": "377", "year": "2017" }, { "DOI": "10.1038/s41572-019-0069-0", "author": "MA Matthay", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Nat Rev Dis Primers", "key": "662_CR52", "unstructured": "Matthay MA, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5(1):1–22.", "volume": "5", "year": "2019" }, { "DOI": "10.1007/s00134-021-06416-z", "author": "TAC Snow", "doi-asserted-by": "publisher", "first-page": "641", "issue": "6", "journal-title": "Intensive Care Med", "key": "662_CR53", "unstructured": "Snow TAC, et al. Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials. Intensive Care Med. 2021;47(6):641–52.", "volume": "47", "year": "2021" }, { "DOI": "10.3390/ijerph18179149", "author": "N Mahroum", "doi-asserted-by": "publisher", "first-page": "9149", "issue": "17", "journal-title": "Int J Environ Res Public Health", "key": "662_CR54", "unstructured": "Mahroum N, et al. Systematic review and meta-analysis of tocilizumab therapy versus standard of care in over 15,000 COVID-19 pneumonia patients during the first eight months of the pandemic. Int J Environ Res Public Health. 2021;18(17):9149.", "volume": "18", "year": "2021" }, { "DOI": "10.7759/cureus.10869", "doi-asserted-by": "crossref", "key": "662_CR55", "unstructured": "Kotak, S., et al., Use of tocilizumab in COVID-19: a systematic review and meta-analysis of current evidence. Cureus, 2020. 12(10)." } ], "reference-count": 55, "references-count": 55, "relation": {}, "resource": { "primary": { "URL": "https://joppp.biomedcentral.com/articles/10.1186/s40545-023-00662-w" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Pharmacy", "Health Policy" ], "subtitle": [], "title": "Does tocilizumab have an effect on the clinical outcomes in COVID-19 patients? A meta-analysis of randomized control trials", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1007/springer_crossmark_policy", "volume": "16" }