Effective treatment of severe COVID-19 patients with tocilizumab

Edited by Zhu Chen, Shanghai Jiao Tong University, Shanghai, China, and approved April 14, 2020 (received for review March 25, 2020)
April 29, 2020
117 (20) 10970-10975

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.

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Acknowledgments

This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province Grant 202004a07020001 and China National Center for Biotechnology Development 175 Grant 2020YFC0843800.

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 117 | No. 20
May 19, 2020
PubMed: 32350134

Classifications

Submission history

Published online: April 29, 2020
Published in issue: May 19, 2020

Keywords

  1. tocilizumab
  2. interleukin-6
  3. COVID-19
  4. SARS-CoV-2
  5. cytokine storm

Acknowledgments

This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province Grant 202004a07020001 and China National Center for Biotechnology Development 175 Grant 2020YFC0843800.

Notes

This article is a PNAS Direct Submission.

Authors

Affiliations

Respiratory 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;
Respiratory and Critical Care Medicine, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 230000, People’s Republic of China;
Tiantian Li
Respiratory 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;
Wei Sun
Respiratory and Critical Care Medicine, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 230000, People’s Republic of China;
Respiratory 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;
Binqing Fu
Institute 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;
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
Yonggang Zhou
Institute 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;
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
Xiaohu Zheng
Institute 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;
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;
Intensive 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;
Xiuyong Li
Hemodialysis Center, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 236000, People’s Republic of China
Xiaohua Zhang
Respiratory and Critical Care Medicine, Anhui Fuyang Second People’s Hospital, Fuyang, Anhui 230000, People’s Republic of China;
Aijun Pan
Intensive 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;
Institute 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;
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230000, People’s Republic of China;

Notes

2
To whom correspondence may be addressed. Email: [email protected] or [email protected].
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.
1
X.X. and M.H. contributed equally to this work.

Competing Interests

The authors declare no competing interest.

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    Effective treatment of severe COVID-19 patients with tocilizumab
    Proceedings of the National Academy of Sciences
    • Vol. 117
    • No. 20
    • pp. 10615-11184

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