Concordance of B‐ and T‐cell responses to SARS‐CoV‐2 infection, irrespective of symptoms suggestive of COVID‐19

  1. Marc F. Österdahl
  2. Eleni Christakou
  3. Deborah Hart
  4. Ffion Harris
  5. Yasaman Shahrabi
  6. Emily Pollock
  7. Muntaha Wadud
  8. Tim D. Spector
  9. Matthew A. Brown
  10. Jeffrey Seow
  11. Michael H. Malim
  12. Claire J. Steves
  13. Katie J. Doores
  14. Emma L. Duncan
  15. Timothy Tree

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Abstract

This study assessed T‐cell responses in individuals with and without a positive antibody response to SARS‐CoV‐2, in symptomatic and asymptomatic individuals during the COVID‐19 pandemic. Participants were drawn from the TwinsUK cohort, grouped by (a) presence or absence of COVID‐associated symptoms (S+, S−), logged prospectively through the COVID Symptom Study app, and (b) anti‐IgG Spike and anti‐IgG Nucleocapsid antibodies measured by ELISA (Ab+, Ab−), during the first wave of the UK pandemic. T‐cell helper and regulatory responses after stimulation with SARS‐CoV‐2 peptides were assessed. Thirty‐two participants were included in the final analysis. Fourteen of 15 with IgG Spike antibodies had a T‐cell response to SARS‐CoV‐2‐specific peptides; none of 17 participants without IgG Spike antibodies had a T‐cell response ( χ 2 : 28.2, p  < 0.001). Quantitative T‐cell responses correlated strongly with fold‐change in IgG Spike antibody titer ( ρ  = 0.79, p  < 0.0001) but not to symptom score ( ρ  = 0.17, p  = 0.35). Humoral and cellular immune responses to SARS‐CoV‐2 are highly correlated. We found no evidence of cellular immunity suggestive of SARS‐CoV2 infection in individuals with a COVID‐19‐like illness but negative antibodies.

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  1. Version published to 10.1002/jmv.28016
  2. ScreenIT

    SciScore for 10.1101/2022.02.03.22270393: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics: The TwinsUK study was approved by NHS London – London-Westminster Research Ethics Committee (REC reference EC04/015), and Guy ‘s and St Thomas ‘ NHS Foundation Trust Research and Development (R&D).
    Consent: All participants provide written, informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum samples were tested for IgG antibody against SARS-CoV-2 Spike protein.
    SARS-CoV-2 Spike protein.
    suggested: None
    Subsequently, individuals were selected to form four groups, defined by symptom score and IgG Spike antibody responses from the initial home visit: symptom-positive, antibody-positive; symptom-positive, antibody-negative; symptom-negative, antibody-positive (i.e., asymptomatic infection); and symptom-negative, antibody-negative (i.e., control group).
    symptom-negative, antibody-negative (i.e., control group)
    suggested: None
    antibody-negative (i.e.
    suggested: None
    Response to the S1 protein subunit is most comparable with IgG-S antibody testing.
    IgG-S
    suggested: None
    PBMC (1-2×106 /stimuli) were incubated for 18h at 37°C in 48-well plates in X-Vivo media (Lonza) supplemented with 5% human AB serum (Sigma) and 0.4μg/mL anti-CD40 antibody (BioXcell).
    anti-CD40
    suggested: (Bio X Cell Cat# BE0016-2, RRID:AB_1107647)
    Software and Algorithms
    SentencesResources
    Superantigen Enterotoxin B (SEB) at 100ng/mL (Sigma Aldrich) was used as a positive control; Infanrix, a hexa-vaccine (GlaxoSmithKline) and Influvac, an Influenza surface antigen vaccine (Abbott Biologicals) were combined (HA + INF) and used to examine anamnestic responses induced by vaccination or infection.
    Abbott Biologicals
    suggested: None
    Samples were acquired on a LSRFortessa Flow Analyser (BD Biosciences) and analysed using the software FlowJo (TreeStar Inc., version 10.7.2).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.02.03.22270393 on medRxiv