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Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis
Chuang Guo.
Bin Li.
Huan Ma.
Xiaofang Wang.
Pengfei Cai.
Qiaoni Yu.
Lin Zhu.
Liying Jin.
Chen Jiang.
Jingwen Fang.
Qian Liu.
Dandan Zong.
Wen Zhang.
Yichen Lu.
Kun Li.
Xuyuan Gao.
Binqing Fu.
Lianxin Liu.
Xiaoling Ma.
Jianping Weng.
Haiming Wei.
Tengchuan Jin.
Jun Lin.
Kun Qu.
Acceso Abierto
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.
Appears in Collections:Artículos científicos

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