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      Repurposed Tocilizumab in Patients with Severe COVID-19

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          Key Points

          • Tocilizumab could prolong survival among hospitalized patients with severe COVID-19.

          • Tocilizumab weakens the inflammatory response while sustaining immune responses.

          • During the tocilizumab treatment, no severe adverse drug reactions were reported.

          Abstract

          The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25–0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11–0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19–induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

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          Author and article information

          Journal
          J Immunol
          J Immunol
          jimmunol
          jimmunol
          JI
          The Journal of Immunology Author Choice
          AAI
          0022-1767
          1550-6606
          1 February 2021
          9 December 2020
          : 206
          : 3
          : 599-606
          Affiliations
          [* ]Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China;
          []Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China;
          []Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
          [§ ]Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; and
          []Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan 430030, China
          Author notes
          [1]

          J.T., M.Z., and M.J. contributed equally to this work.

          Address correspondence and reprint requests to Prof. Ke Hu, Prof. Xiaoping Miao, or Prof. Huilan Zhang, Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan 430060, Hubei, China (K.H.), Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Hang Kong Road No. 13, Han Kou District, Wuhan 430030, Hubei, China (X.M.), or Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Road, Han Kou District, Wuhan 430030, Hubei, China (H.Z.). E-mail addresses: huke-rmhospital@ 123456163.com (K.H.), miaoxp@ 123456hust.edu.cn (X.M.), or huilanz_76@ 123456163.com (H.Z.)
          Author information
          http://orcid.org/0000-0002-4641-0262
          http://orcid.org/0000-0002-8433-2402
          http://orcid.org/0000-0001-9862-7239
          http://orcid.org/0000-0002-6818-9722
          http://orcid.org/0000-0002-2366-7321
          Article
          PMC7812057 PMC7812057 7812057 ji_2000981
          10.4049/jimmunol.2000981
          7812057
          33298617
          45c4b4a9-9c09-45ac-901c-f039d5b27140
          Copyright © 2021 by The American Association of Immunologists, Inc.

          This article is distributed under The American Association of Immunologists, Inc., Reuse Terms and Conditions for Author Choice articles .

          History
          : 26 August 2020
          : 20 November 2020
          Page count
          Figures: 2, Tables: 3, Equations: 0, References: 42, Pages: 8
          Funding
          Funded by: Huazhong University of Science and Technology, DOI https://doi.org/10.13039/501100003397;
          Award ID: 2020kfyXGYJ043
          Funded by: National Key Research and Development Plan for the Emergency Management
          Award ID: 2020YFC0845100
          Categories
          Infectious Disease and Host Response

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