RT Journal Article
SR Electronic
T1 Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.08.029769
DO 10.1101/2020.04.08.029769
A1 Chuang Guo
A1 Bin Li
A1 Huan Ma
A1 Xiaofang Wang
A1 Pengfei Cai
A1 Qiaoni Yu
A1 Lin Zhu
A1 Liying Jin
A1 Chen Jiang
A1 Jingwen Fang
A1 Qian Liu
A1 Dandan Zong
A1 Wen Zhang
A1 Yichen Lu
A1 Kun Li
A1 Xuyuan Gao
A1 Binqing Fu
A1 Lianxin Liu
A1 Xiaoling Ma
A1 Jianping Weng
A1 Haiming Wei
A1 Tengchuan Jin
A1 Jun Lin
A1 Kun Qu
YR 2020
UL http://biorxiv.org/content/early/2020/04/09/2020.04.08.029769.abstract
AB Coronavirus disease 2019 (COVID-19) has caused more than 40,000 deaths worldwide1. Approximately 14% of patients with COVID-19 experienced severe disease and 5% were critically ill2. Studies have shown that dysregulation of the COVID-19 patients’ immune system may lead to inflammatory storm and cause severe illness and even death3,4. Tocilizumab treatment targeting interleukin 6 receptor has shown inspiring clinical results of severe COVID-19 patients5. However, the immune network with Tocilizumab treatment at single cell resolution has not been uncovered. Here, we profiled the single-cell transcriptomes of 13,289 peripheral blood mononuclear cells isolated at three longitudinal stages from two severe COVID-19 patients treated with Tocilizumab. We identified a severe stage-specific monocyte subpopulation and these cells centric immune cell interaction network connected by the inflammatory cytokines and their receptors. The over-activated inflammatory immune response was attenuated after Tocilizumab treatment, yet immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in recovered COVID-19 patients. These results provided critical insights into the immunopathogenesis of severe COVID-19 and revealed fundamentals of effectiveness in Tocilizumab treatment.