Single-cell analysis of severe COVID-19 patients reveals a monocyte-driven inflammatory storm attenuated by Tocilizumab

  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

Despite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8 + T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.

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  1. 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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  2. Version published to 10.1101/2020.04.08.029769 on bioRxiv