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

  1. Chuang Guo
  2. Bin Li
  3. Huan Ma
  4. Xiaofang Wang
  5. Pengfei Cai
  6. Qiaoni Yu
  7. Lin Zhu
  8. Liying Jin
  9. Chen Jiang
  10. Jingwen Fang
  11. Qian Liu
  12. Dandan Zong
  13. Wen Zhang
  14. Yichen Lu
  15. Kun Li
  16. Xuyuan Gao
  17. Binqing Fu
  18. Lianxin Liu
  19. Xiaoling Ma
  20. Jianping Weng
  21. Haiming Wei
  22. Tengchuan Jin
  23. Jun Lin
  24. Kun Qu

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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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  1. Version published to 10.1038/s41467-020-17834-w
  2. Version published to 10.1101/2020.04.08.029769v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.04.08.029769: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The thickness of line connecting TFs and target genes represented the weight of regulatory link predicted by SCENIC.
    SCENIC
    suggested: (SCENIC, RRID:SCR_017247)
    In CellphoneDB, a permutation test was used to evaluate the significance of a cytokine/receptor pair.
    CellphoneDB
    suggested: (CellPhoneDB, RRID:SCR_017054)
    Metascape utilizes the hypergeometric test and Benjamini-Hochberg P value correction algorithm to identify the ontology terms that contain a statistically greater number of genes in common than expected.
    Metascape
    suggested: (Metascape, RRID:SCR_016620)
    Data Availability: The scRNA-seq data of PBMCs from the 2 severe COVID-19 patients can be obtained from the Genome Sequence Archive (GSA) at BIG Data Center and the accession number is CRA002509.
    Genome Sequence Archive
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  4. Version published to 10.1101/2020.04.08.029769v1 on bioRxiv