Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients

  1. Xiang-Na Zhao
  2. Yue You
  3. Xiao-Ming Cui
  4. Hui-Xia Gao
  5. Guo-Lin Wang
  6. Sheng-Bo Zhang
  7. Lin Yao
  8. Li-Jun Duan
  9. Ka-Li Zhu
  10. Yu-Ling Wang
  11. Li Li
  12. Jian-Hua Lu
  13. Hai-Bin Wang
  14. Jing-Fang Fan
  15. Huan-Wei Zheng
  16. Er-Hei Dai
  17. Lu-Yi Tian
  18. Mai-Juan Ma

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Abstract

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56 bri CD16 − natural killer (NK) cells and upregulation of interferon-gamma in effector CD4 + and CD8 + T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4 + T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.

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  1. Version published to 10.1038/s41392-021-00753-7
  2. ScreenIT

    SciScore for 10.1101/2020.09.02.276865: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics statement: The study was conducted following the Declaration of Helsinki, and the Institutional Review Board of the Academy of Military Medical Sciences approved the study protocol (IRB number: AF/SC-08/02.46).
    Consent: All patients or their surrogates provided written informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Non-protein-coding genes and genes related to sex were removed in the counts before being analyzed by edgeR (3.28.1) (Robinson et al., 2010). glmQLFit and glmQLFTest from edgeR were used to find marker genes between each condition.
    edgeR
    suggested: (edgeR, RRID:SCR_012802)
    GO analysis was conducted on upregulated genes using topGO (3.28.1) (Alexa et al., 2006), and the top 10 enriched GO terms were plotted.
    topGO
    suggested: (topGO, RRID:SCR_014798)
    All plots were generated using ggplot2 (3.3.1) (Wickham, 2016), and heatmaps were generated using pheatmap (1.0.12) unless otherwise specified.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    pheatmap
    suggested: (pheatmap, RRID:SCR_016418)

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

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are several limitations to this study. Our sample size is relatively small,with only one severe and two asymptomatic patients. In addition, only early-stage blood samples were available from the severe patient. Therefore, future studies with longitudinal samples from more COVID-19 patients, especially for asymptomatic patients, are needed to further identify the relationships between immune characteristic and asymptomatic infection. Second, only blood samples from patients were used for immunological analyses, but not bronchoalveolar lavage fluid samples because of the difficulty of obtaining these samples due to biosafety reasons. Overall, our analyses provide the first comprehensive characterization of the immune landscape of asymptomatic COVID-19 patients and highlight the importance of innate immune response towards disease progression. The reduced abundance of CD56briCD16− NK subset in the early-stage severe patient suggested avenues for both diagnostic and clinical intervention at the early stages of the disease, considering drugs such as Natalizumab could induce the expansion of CD56briCD16− NK cells (Skarica et al., 2011).

    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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  3. Version published to 10.1101/2020.09.02.276865v1 on bioRxiv