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Research Article

Effective treatment of severe COVID-19 patients with tocilizumab

Xiaoling Xu, View ORCID ProfileMingfeng Han, Tiantian Li, Wei Sun, View ORCID ProfileDongsheng Wang, Binqing Fu, Yonggang Zhou, Xiaohu Zheng, View ORCID ProfileYun Yang, Xiuyong Li, Xiaohua Zhang, Aijun Pan, and Haiming Wei
PNAS May 19, 2020 117 (20) 10970-10975; first published April 29, 2020; https://doi.org/10.1073/pnas.2005615117
Xiaoling Xu
aRespiratory and Critical Care Medicine, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230000, People’s Republic of China;
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  • For correspondence: xxlahh08@163.com ustcwhm@ustc.edu.cn
Mingfeng Han
bRespiratory and Critical Care Medicine, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 230000, People’s Republic of China;
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  • ORCID record for Mingfeng Han
Tiantian Li
aRespiratory and Critical Care Medicine, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230000, People’s Republic of China;
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Wei Sun
bRespiratory and Critical Care Medicine, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 230000, People’s Republic of China;
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Dongsheng Wang
aRespiratory and Critical Care Medicine, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230000, People’s Republic of China;
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Binqing Fu
cInstitute of Immunology and the Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
dHefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
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Yonggang Zhou
cInstitute of Immunology and the Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
dHefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
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Xiaohu Zheng
cInstitute of Immunology and the Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
dHefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
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Yun Yang
eIntensive Care Unit, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230000, People’s Republic of China;
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Xiuyong Li
fHemodialysis Center, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 236000, People’s Republic of China
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Xiaohua Zhang
bRespiratory and Critical Care Medicine, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 230000, People’s Republic of China;
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Aijun Pan
eIntensive Care Unit, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui 230000, People’s Republic of China;
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Haiming Wei
cInstitute of Immunology and the Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
dHefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
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  • For correspondence: xxlahh08@163.com ustcwhm@ustc.edu.cn
  1. Edited by Zhu Chen, Shanghai Jiao Tong University, Shanghai, China, and approved April 14, 2020 (received for review March 25, 2020)

This article has Letters. Please see:

  • Safety concerns regarding concomitant use of tocilizumab and glucocorticoids in COVID-19 patients - November 12, 2020
  • Does tocilizumab have a magical therapeutic effect on COVID-19 patients without obvious adverse reactions? - November 17, 2020

See related content:

  • Reply to Yang et al.: Tocilizumab treatment in COVID-19 patients needs the assessment of the disease severity and timely intervention
    - Nov 12, 2020
  • Reply to Wang et al.: Tocilizumab treatment should be used in a timely manner, at suitable dose, and in suitable patients
    - Nov 17, 2020
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Significance

In patients with coronavirus disease 2019, a large number of T lymphocytes and mononuclear macrophages are activated, producing cytokines such as interleukin-6 (IL-6), which bind to the IL-6 receptor on the target cells, causing the cytokine storm and severe inflammatory responses in lungs and other tissues and organs. Tocilizumab, as a recombinant humanized anti-human IL-6 receptor monoclonal antibody, can bind to the IL-6 receptor with high affinity, thus preventing IL-6 itself from binding to its receptor, rendering it incapable of immune damage to target cells, and alleviating the inflammatory responses.

Abstract

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

  • tocilizumab
  • interleukin-6
  • COVID-19
  • SARS-CoV-2
  • cytokine storm

Footnotes

  • ↵1X.X. and M.H. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: xxlahh08{at}163.com or ustcwhm{at}ustc.edu.cn.
  • Author contributions: X.X. and H.W. designed research; M.H., W.S., D.W., Y.Z., X. Zheng, Y.Y., X.L., X. Zhang, and A.P. performed research; X.X., T.L., B.F., and H.W. analyzed data; and X.X., T.L., B.F., and H.W. wrote the paper.

  • The authors declare no competing interest.

  • This article is a PNAS Direct Submission.

  • Copyright © 2020 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

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Effective treatment of severe COVID-19 patients with tocilizumab
Xiaoling Xu, Mingfeng Han, Tiantian Li, Wei Sun, Dongsheng Wang, Binqing Fu, Yonggang Zhou, Xiaohu Zheng, Yun Yang, Xiuyong Li, Xiaohua Zhang, Aijun Pan, Haiming Wei
Proceedings of the National Academy of Sciences May 2020, 117 (20) 10970-10975; DOI: 10.1073/pnas.2005615117

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Effective treatment of severe COVID-19 patients with tocilizumab
Xiaoling Xu, Mingfeng Han, Tiantian Li, Wei Sun, Dongsheng Wang, Binqing Fu, Yonggang Zhou, Xiaohu Zheng, Yun Yang, Xiuyong Li, Xiaohua Zhang, Aijun Pan, Haiming Wei
Proceedings of the National Academy of Sciences May 2020, 117 (20) 10970-10975; DOI: 10.1073/pnas.2005615117
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