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

doi:10.1073/pnas.2005615117

New Research In

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:

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

See related content:

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

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.

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.

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

View Full Text