Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm

Guo, Chuang; Li, Bin; Ma, Huan; Wang, Xiaofang; Cai, Pengfei; Yu, Qiaoni; Zhu, Lin; Jin, Liying; Jiang, Chen; Fang, Jingwen; Liu, Qian; Zong, Dandan; Zhang, Wen; Lu, Yichen; Li, Kun; Gao, Xuyuan; Fu, Binqing; Liu, Lianxin; Ma, Xiaoling; Weng, Jianping; Wei, Haiming; Jin, Tengchuan; Lin, Jun; Qu, Kun

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8(+) T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.