Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

  1. Anna E. Oja
  2. Anno Saris
  3. Cherien A. Ghandour
  4. Natasja A.M. Kragten
  5. Boris M. Hogema
  6. Esther J. Nossent
  7. Leo M.A. Heunks
  8. Susan Cuvalay
  9. Ed Slot
  10. Francis H. Swaneveld
  11. Hans Vrielink
  12. Theo Rispens
  13. Ellen van der Schoot
  14. René A.W. van Lier
  15. Anja Ten Brinke
  16. Pleun Hombrink

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.18.159202: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Ethics approval: Data and samples were collected only from voluntary, non-remunerated, adult donors who provided written informed consent as part of routine donor selection and blood collection procedures, that were approved by the Ethics Advisory Council of Sanquin Blood Supply Foundation.
    IACUC: The Amsterdam UMC COVID-19 biobank stores leftover patients samples that were collected for diagnostics purposes, which is approved by Review Committee Biobank of the Amsterdam UMC (2020-065).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Flow cytometric analysis: PBMCs and BALF MCs were stained with combinations of the following antibodies: anti-CD3 BUV661 (BD, clone UCHT1), anti-CD4 BUV737 (BD, clone SK3), anti-CD8 BUV805 (BD, clone SK1), anti-CD45RA BUV563 (BD, clone HI100), anti-CD27 BV650 (Biolegend, clone O323), anti-CD69 BUV395 (BD, clone FN50), anti-CD103 BV711 (Biolegend, clone Ber-ACT8), anti-PD-1 BB700 (BD, clone EH12.1), anti-CXCR5 AF488 (BD, clone RF8B2), anti-ICOS BV711 (Biolegend, clone C398.4A), anti-CD40L PeDazzle594 (Biolegend, clone 24-31), anti-CD137 PeCy7 (Thermofisher Scientific, clone 4B4-1), anti-TNF BV510 (Biolegend, clone Mab11), anti-IFNγ BV785 (Biolegend, clone 4S.B3), anti-IL17a BV605 (Biolegend, clone BL168), anti-IL-4 BV421 (Biolegend, clone MP4-25D2), and anti-IL-21 eFluor660 (Thermofisher, clone 3A3-N2).
    anti-CD3
    suggested: (SouthernBiotech Cat# 8200-30, RRID:AB_2796425)
    anti-CD4
    suggested: (Cell Sciences Cat# 873.018.050, RRID:AB_10052620)
    anti-CD8
    suggested: (SouthernBiotech Cat# 9536-30, RRID:AB_2796895)
    anti-CD45RA
    suggested: (BioLegend Cat# 304139, RRID:AB_2561369)
    anti-CD27
    suggested: (BioLegend Cat# 124233, RRID:AB_2687192)
    anti-CD69
    suggested: (SouthernBiotech Cat# 1715-30, RRID:AB_2795186)
    anti-CD103 BV711
    suggested: None
    anti-PD-1
    suggested: None
    anti-CXCR5
    suggested: (BD Biosciences Cat# 552032, RRID:AB_394324)
    anti-ICOS BV711
    suggested: None
    anti-CD40L
    suggested: None
    anti-CD137
    suggested: (BD Biosciences Cat# 740134, RRID:AB_2739891)
    anti-TNF
    suggested: None
    anti-IFNγ
    suggested: None
    anti-IL17a
    suggested: None
    anti-IL-4 BV421
    suggested: (BioLegend Cat# 500825, RRID:AB_10898316)
    anti-IL-21
    suggested: None
    Software and Algorithms
    SentencesResources
    Data analysis was performed using FlowJo (TreeStar, Version 10.0.7).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistics: One- and two-way ANOVA and Tukey’s multiple comparisons test using GraphPad Prism 8 were used to determine the significance of our results as indicated in figure legends.
    GraphPad Prism
    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: 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.
    • 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 10.1101/2020.06.18.159202v1 on bioRxiv