Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients

  1. Anthony T. Tan
  2. Martin Linster
  3. Chee Wah Tan
  4. Nina Le Bert
  5. Wan Ni Chia
  6. Kamini Kunasegaran
  7. Yan Zhuang
  8. Christine Y.L. Tham
  9. Adeline Chia
  10. Gavin J.D. Smith
  11. Barnaby Young
  12. Shirin Kalimuddin
  13. Jenny G.H. Low
  14. David Lye
  15. Lin-Fa Wang
  16. Antonio Bertoletti

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Abstract

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  1. Version published to 10.1016/j.celrep.2021.108728
  2. ScreenIT

    SciScore for 10.1101/2020.10.15.341958: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All participants provided written informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableSix patients were male, six were female, their median age at time of admission was 52.5 years, ranging from 27 to 78 years.

    Table 2: Resources

    Antibodies
    SentencesResources
    Luminex analysis: SARS-CoV-2 RBD, S1 and N proteins (Genscript) were conjugated onto MagPlex microsphere (Luminex) using xMAP antibody coupling kit (Luminex).
    xMAP
    suggested: None
    SARS-CoV-2 spike and N proteins specific antibodies were detected by pre-incubation of 100-fold diluted serum (in 1% BSA PBS) with conjugated microspheres (1250 beads/antigen) for 1h at room temperature, followed by 1:1000 diluted PE-conjugated anti-human IgG polyclonal antibody (eBioscience) or PE-conjugated anti-human IgM antibody for 1h at room temperature.
    anti-human IgG
    suggested: None
    anti-human IgM
    suggested: None
    IFN-γ ELISPOT assay: 15-mer peptides that spanned the entire ORF of genes eight SARS-CoV-2 proteins (NP, M, ORF7, ORF8, ORF3, S, NSP7, NSP13) and antibody responses to two SARS-CoV-2 proteins (NP, S) were synthesised with 10 amino acids overlap and were grouped into pools of approximately 40 peptides (Table S1).
    NSP7
    suggested: (Abcam Cat# ab21660, RRID:AB_874019)
    NSP13
    suggested: None
    Biotinylated anti-IFN-γ antibody (MabTech) at a 1:2000 dilution in PBS/0.5% FCS was incubated at RT for two hours, followed by six wash steps with PBS and incubation of Streptavidin-AP (MabTech) at a 1:2000 dilution in PBS/0.5% FCS at RT for one hour.
    anti-IFN-γ
    suggested: None
    Cells were stained with the yellow LIVE/DEAD fixable dead cell stain kit (Invitrogen) and anti-CD3 (clone SK7; 3:50), anti-CD4 (clone SK3; 3:50), and anti-CD8 (clone SK1; 3:50) antibodies..
    anti-CD3
    suggested: None
    anti-CD4
    suggested: None
    anti-CD8
    suggested: None
    Cells were subsequently fixed and permeabilised using the Cytofix/Cytoperm kit (BD Biosciences-Pharmingen) and stained with anti-IFN-γ (clone 25723, R&D Systems; 1:25) and anti-TNF-α (clone MAb11; 1:25) antibodies and analysed on a BD-LSR II FACS Scan.
    anti-TNF-α
    suggested: None
    Software and Algorithms
    SentencesResources
    Study design: Patients (n=12) were enrolled in this study after being admitted to the hospital and confirmed to be infected with SARS-CoV-2 based on a positive SARS-CoV-2 RT-PCR test as part of the PROTECT (National Healthcare Group Domain Specific Review Board reference number 2012/00917) and Novel Pathogens (CIRB ref.
    National Healthcare
    suggested: None
    Statistical analysis: Regression analyses were performed using GraphPad Prism v7 software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Figures were prepared in Adobe Illustrator Creative Cloud.
    Adobe Illustrator
    suggested: (Adobe Illustrator, RRID:SCR_010279)

    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.
    • No funding statement was detected.
    • 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.

  3. Version published to 10.1101/2020.10.15.341958v1 on bioRxiv