Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing

  1. Wen Wen
  2. Wenru Su
  3. Hao Tang
  4. Wenqing Le
  5. Xiaopeng Zhang
  6. Yingfeng Zheng
  7. Xiuxing Liu
  8. Lihui Xie
  9. Jianmin Li
  10. Jinguo Ye
  11. Liwei Dong
  12. Xiuliang Cui
  13. Yushan Miao
  14. Depeng Wang
  15. Jiantao Dong
  16. Chuanle Xiao
  17. Wei Chen
  18. Hongyang Wang

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Abstract

COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14 ++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14 ++ IL1β + monocytes in the ERS. CD4 + T cells and CD8 + T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development were confirmed. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity, which had not been reported yet. Furthermore, integrated analysis predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting COVID-19 patients are still vulnerable after hospital discharge. Identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.23.20039362: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: A written informed consent was regularly obtained from all patients.
    IRB: The study was approved by the Ethics Committee of Wuhan Hankou Hospital,
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe 10 patients consisted of five males and five females and ranged from ages 40 to 70 years old, with a median of 50 years old.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The genes used in PCA analysis have eliminated mitochondria (MT), and ribosomes (RPL and RPS) genes including MT-ND3, MT-ATP8, RPS15A, RPS28, RPS21, RPS27, RPS29, RPL36, RPL34,
    MT-ND3
    suggested: ECACC Cat# 92090901, RRID:CVCL_4258)
    MT-ATP8
    suggested: None
    Software and Algorithms
    SentencesResources
    The FastQC software was used for quality check.
    FastQC
    suggested: (FastQC, RRID:SCR_014583)
    ), KEGG pathway analyses were performed using Metascape webtool (www.metascape.org).
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Metascape
    suggested: (Metascape, RRID:SCR_016620)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1038/s41421-020-0168-9
  3. Version published to 10.1101/2020.03.23.20039362v2 on medRxiv
  4. Version published to 10.1101/2020.03.23.20039362v1 on medRxiv