Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

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

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Abstract

Recent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56 bri CD16 − NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8 + T cells but had a robust effector CD4 + T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4 + T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2 . Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.

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  1. 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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  2. Version published to 10.1101/2020.09.02.276865 on bioRxiv