Impaired T cell functions along with elevated activated Tregs at the early stage of asymptomatic SARS-CoV-2 infection

  1. Jingyi Yang
  2. Ejuan Zhang
  3. Maohua Zhong
  4. Qingyu Yang
  5. Ke Hong
  6. Ting Shu
  7. Dihan Zhou
  8. Jie Xiang
  9. Jianbo Xia
  10. Xi Zhou
  11. Dingyu Zhang
  12. Chaolin Huang
  13. You Shang
  14. Huimin Yan

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Abstract

Background

Limited data are available on the T cell responses for the asymptomatic SARS-CoV-2 infection case.

Methods

An imported SARS-CoV-2 infection case in Wuhan was admitted in hospital for quarantine and observation. The T cell responses were followed up by flow cytometry analysis of the peripheral blood nonnuclear cells (PBMCs) at days 7, 13, 22, and 28 after admission.

Findings

We found the imported SARS-CoV-2 infection in Wuhan is an asymptomatic case. His T cell differentiation, proliferation and activation matched the classical kinetics of T cell responses induced by viral infection, but the activation maintained at a relatively low level. Function analysis indicated frequencies of IFN-γ producing CD4 + and CD8 + T cells were notably lower than that of the healthy controls (HC) at day 7, and then rebound gradually. But IFN-γ + CD8 + T cells were detained at a significant lower level even at day 28, when the SARS-CoV-2 virus had already become undetectable for 3 weeks. Moreover, percentage of IL-17 producing CD4 + T cells was also detained constantly at a much lower level compared to HC. At day 7, although percentage of Tregs was in normal range, the frequency of activated Treg (aTreg) was remarkably as high as 4·4-fold of that in HC.

Interpretation

The T cell activation in the asymptomatic SARS-CoV-2 infection experienced a significant suppression and presented impairment of Th1/Th17 and CD8 + T cell functions. Early elevation of the aTregs might play role in the activation and function of T cells in the asymptomatic SARS-CoV-2 infection.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.25.20108852: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was reviewed and approved by the Medical Ethical Committee of Wuhan Jinyintan hospital (approval number KY-2020-47·01).
    Consent: Written informed consent was obtained from the patient and the healthy controls.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableEleven healthy age-matched male volunteers were enrolled as healthy controls.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    A BD LSR Fortessa flow cytometer (Becton Dickinson) was used to assess the stained cells and data were analyzed using FlowJo V7·0.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis: Data analysis was carried out with InStat, version 5·0 (GraphPad Software, La Jolla, CA, USA) and the data of healthy controls were presented as mean ± SD with dot plots.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We detected the following sentences addressing limitations in the study:
    The present study has some limitations. First, there was only one case in this longitudinal prospective study. The characteristics of T cell response should be confirmed further in larger cohorts of people with asymptomatic SARS-CoV-2 infection. Second, T cell functions were analyzed using polyclonal stimulator PMA and Ionomycin that indicated the potential function of T cell reservoir. The quantity and quality of viral-specific T cells that directly related to the viral control have to be further studied in the patients with different disease severities. Hopefully, we may have some more answers in our following cohort studies. In conclusion, the SARS-CoV-2 asymptomatic infection induced low activation and impaired function of CD4+ and CD8+ T cells exemplified by suppressed IFN-γ production in both CD4+ T and CD8+ T cells and inhibited IL-17 production in CD4+ T cells. In addition, the elevation of aTreg at early infection stage suggested an aberrant Treg activation and a unique immune pathology of the SARS-CoV-2 virus. Our study shed some light on early interaction between the SARS-CoV-2 infection and host immune responses, which might give us more insights into the preventive and curative immune strategy.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 16 and 15. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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 10.1101/2020.05.25.20108852 on medRxiv