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

• Published in: Nature communications Vol. 11; no. 1; pp. 3924 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.08.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 49/91; 631/114; 631/250/2499; 631/250/2504/342; 631/250/256/2516; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antiviral agents; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Betacoronavirus - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Computational Biology; Coronavirus Infections - blood; Coronavirus Infections - drug therapy; Coronavirus Infections - immunology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Cytokine storm; Cytokines; Cytokines - blood; Cytokines - immunology; Drug delivery; Gene sequencing; Humanities and Social Sciences; Humans; Immune response (humoral); Immune system; Immunosuppressive agents; Inflammation; Inflammation - drug therapy; Interleukin 6; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages - drug effects; Macrophages - immunology; Monoclonal antibodies; Monocytes; Monocytes - immunology; multidisciplinary; Pandemics; Pneumonia, Viral - blood; Pneumonia, Viral - drug therapy; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; Receptors, Interleukin-6 - immunology; Remission; Ribonucleic acid; RNA; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Single-Cell Analysis - methods; Target recognition
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17834-w

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. Tocilizumab has been used to treat the excessive inflammatory responses in COVID-19 patients. Here, the authors use single-cell RNA sequencing results from two severe COIVD-19 patients to provide high-dimensional immune profiling data, and to implicate potential cellular and molecular insights for the therapeutic effects of tocilizumab.