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Nature communications
08 06, 2020;11 (1): 3924.

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

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
Author Information
  1. Chuang Guo: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China. ORCID
  2. Bin Li: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  3. Huan Ma: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  4. Xiaofang Wang: Department of Hepatobiliary Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  5. Pengfei Cai: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  6. Qiaoni Yu: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  7. Lin Zhu: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  8. Liying Jin: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  9. Chen Jiang: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  10. Jingwen Fang: HanGene Biotech, Xiaoshan Innovation Polis, 31200, Hangzhou, Zhejiang, China.
  11. Qian Liu: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  12. Dandan Zong: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  13. Wen Zhang: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  14. Yichen Lu: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  15. Kun Li: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China. ORCID
  16. Xuyuan Gao: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  17. Binqing Fu: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  18. Lianxin Liu: Department of Hepatobiliary Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China.
  19. Xiaoling Ma: Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, China.
  20. Jianping Weng: Department of Endocrinology and Metabolism, The First Affiliated Hospital of USTC, Division of Life Sciences of Medicine, University of Science and Technology of China, 230026, Hefei, China.
  21. Haiming Wei: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China. ORCID
  22. Tengchuan Jin: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China. jint@ustc.edu.cn. ORCID
  23. Jun Lin: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China. linjun7@ustc.edu.cn. ORCID
  24. Kun Qu: Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021, Hefei, Anhui, China. qukun@ustc.edu.cn. ORCID
PMID: 32764665 DOI: 10.1038/s41467-020-17834-w

Abstract

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.

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MeSH Term

Antibodies, Monoclonal, Humanized
B-Lymphocytes
Betacoronavirus
CD8-Positive T-Lymphocytes
COVID-19
Computational Biology
Coronavirus Infections
Cytokines
Humans
Inflammation
Macrophages
Monocytes
Pandemics
Pneumonia, Viral
Receptors, Interleukin-6
SARS-CoV-2
Single-Cell Analysis

Chemicals

Antibodies, Monoclonal, Humanized
Cytokines
IL6R protein, human
Receptors, Interleukin-6
tocilizumab
Journal Article Research Support, Non-U.S. Gov't

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