Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients with acute respiratory distress syndrome

  1. Daniela Weiskopf
  2. Katharina S. Schmitz
  3. Matthijs P. Raadsen
  4. Alba Grifoni
  5. Nisreen M. A. Okba
  6. Henrik Endeman
  7. Johannes P. C. van den Akker
  8. Richard Molenkamp
  9. Marion P. G. Koopmans
  10. Eric C. M. van Gorp
  11. Bart L. Haagmans
  12. Rik L. de Swart
  13. Alessandro Sette
  14. Rory D. de Vries

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Abstract

Peptide pool stimulation enables longitudinal analysis of SARS-CoV-2–specific CD4 + and CD8 + T cells in ICU-admitted COVID-19 patients.

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  1. Version published to 10.1126/sciimmunol.abd2071
  2. ScreenIT

    SciScore for 10.1101/2020.04.11.20062349: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Due to the clinical state of most ARDS patients (i.e. intubated, comatose), deferred proxy consent was obtained instead of direct written informed consent from the patients themselves.
    IACUC: The study protocol was approved by the medical ethical committee of Erasmus MC, Rotterdam, the Netherlands (MEC-2017-417 and MEC-2020-0222).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 RBD ELISA: Serum or plasma samples were analyzed for the presence of SARS-CoV-2 specific antibody responses using a validated in-house SARS-CoV-2 receptor binding domain (RBD) IgG ELISA as previously described(Okba et al., 2020).
    SARS-CoV-2 receptor binding domain (RBD) IgG
    suggested: None
    Briefly, cell culture supernatants were mixed with beads coated with capture antibodies specific for IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFNγ, TNFα, IL-17a, IL-17F, IL-4, IL-21 and IL-22 and incubated for 2 hours.
    IL-5
    suggested: None
    IL-13
    suggested: None
    IL-2
    suggested: None
    IL-6
    suggested: None
    IL-9
    suggested: None
    IL-10
    suggested: (Acris Antibodies GmbH Cat# AP07161PU-N, RRID:AB_1618319)
    TNFα
    suggested: None
    IL-17a
    suggested: (Shenandoah Biotechnology Cat# PAR-100-IL17F-100 ug, RRID:AB_10732297)
    IL-17F
    suggested: (Thermo Fisher Scientific Cat# 88-8419-44, RRID:AB_1944439)
    IL-4
    suggested: None
    IL-21
    suggested: None

    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:
    Due to limitations in the number of PBMC that could be obtained from severe COVID-19 ARDS patients in an ICU setting, we could not resolve which cells were responsible for production of which cytokine by intracellular cytokine staining. Elevated levels of IL-6 in patient plasma have been correlated to respiratory failure in COVID-19 patients (Herold et al., 2020). Although we could not detect increased specific production of IL-6 in PBMC stimulated with peptide pools due high background production in controls (potentially due to in vivo activation), we detected a dominant IL-6 and TNFα response in cell culture supernatants from the patient deceased due to respiratory failure (case 3). To determine the role of T-cells in COVID-19, it is crucial that the cell types responsible for the production of IL-6 and the concomitant ‘cytokine storm’ are identified in large comparative cohort studies. We included PBMC obtained from ten buffycoats obtained before the SARS-CoV-2 pandemic as negative HC. In some instances, reactive T-cells were detected in HC after MP stimulation, both on basis of T-cell activation and cytokine production. Since PBMC from these HC could not contain SARS-CoV-2-specific T-cells, we hypothesize that these responses were cross-reactive and had been induced by circulating seasonal ‘common cold’ coronaviruses. If we consider samples with a SI > 3 as responders, we identified 2 out of 10 HC (20%) to have these cross-reactive T-cells. This is in good accordance with...

    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.

  3. Version published to 10.1101/2020.04.11.20062349v2 on medRxiv
  4. Version published to 10.1101/2020.04.11.20062349v1 on medRxiv