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      Effectiveness of tocilizumab in the treatment of hospitalized adults COVID-19 : A systematic review and meta-analysis

      review-article
      , MD a , , MD b , , MD a , , MD a ,
      Medicine
      Lippincott Williams & Wilkins
      COVID-19, meta-analysis, mortality, tocilizumab

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          Abstract

          Background:

          Since December 2019, the coronavirus disease (COVID-19) has spread worldwide, leading to a global health threat. This study aimed to investigate the effectiveness of tocilizumab in COVID-19 patients.

          Methods:

          We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform to March 10, 2021 for randomized controlled trials in which patients were randomly assigned to receive tocilizumab plus usual care or usual care alone in hospitalized adults with COVID-19. A random-effects meta-analysis model was used to pool studies. All data analyses were performed using Review Manager version 5.4.

          Results:

          Eleven studies with 6579 patients were included in our meta-analysis, of which 3406 and 3173 were assigned to tocilizumab and control groups, respectively. Tocilizumab significantly reduced the 28 to 30-day mortality (relative risk [RR] = 0.89, 95% confidence interval [CI] 0.80-0.99, P = .04), incidence of mechanical ventilation (MV) (RR = 0.79, 95% CI 0.71-0.89, P < .001), composite outcome of MV or death (RR = 0.81, 95% CI 0.72-0.90, P < .001), time-to-hospital discharge (hazard ratio = 1.30, 95% CI 1.16-1.45, P < .001), intensive care unit admission (RR = 0.64, 95% CI 0.47-0.88, P = .006), serious infection (RR = 0.61, 95% CI 0.40-0.94, P = .02), and number of serious adverse events (RR = 0.64, 95% CI 0.47-0.86, P = .004).

          Conclusion:

          Tocilizumab reduced short-term mortality, incidence of MV, composite outcome of death or MV, intensive care unit admission, serious infection, serious adverse events, and time-to-hospital discharge in hospitalized COVID-19 patients. Further studies are required to determine the optimal dose.

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          Most cited references35

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Measuring inconsistency in meta-analyses.

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              Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                04 March 2022
                04 March 2022
                04 March 2022
                : 101
                : 9
                : e28967
                Affiliations
                [a ]Department of Intensive Care Unit, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China
                [b ]Department of Nephrology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China.
                Author notes
                []Correspondence: Jin Yang, Department of Intensive Care Unit, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400013, China (e-mail: springofsilence@ 123456163.com ).
                Article
                MD-D-21-06542 28967
                10.1097/MD.0000000000028967
                8896441
                35244063
                34ffba9f-0007-4d67-8c89-412e1b243212
                Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 24 September 2021
                : 11 January 2022
                : 6 February 2022
                Categories
                4900
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                covid-19,meta-analysis,mortality,tocilizumab
                covid-19, meta-analysis, mortality, tocilizumab

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