TY - JOUR 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 DO - 10.1101/2020.04.08.029769 SP - 2020.04.08.029769 AU - Chuang Guo AU - Bin Li AU - Huan Ma AU - Xiaofang Wang AU - Pengfei Cai AU - Qiaoni Yu AU - Lin Zhu AU - Liying Jin AU - Chen Jiang AU - Jingwen Fang AU - Qian Liu AU - Dandan Zong AU - Wen Zhang AU - Yichen Lu AU - Kun Li AU - Xuyuan Gao AU - Binqing Fu AU - Lianxin Liu AU - Xiaoling Ma AU - Jianping Weng AU - Haiming Wei AU - Tengchuan Jin AU - Jun Lin AU - Kun Qu Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/09/2020.04.08.029769.abstract N2 - 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. ER -