Accuracy and real life performance of a novel interferon-γ release assay for the detection of SARS-CoV2 specific T cell response

  1. Daniela Huzly
  2. Marcus Panning
  3. Franziska Smely
  4. Martin Enders
  5. Johanna Komp
  6. Valeria Falcone
  7. Daniel Steinmann

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Abstract

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  1. Version published to 10.1016/j.jcv.2022.105098
  2. ScreenIT

    SciScore for 10.1101/2021.07.17.21260316: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: The Department of Occupational Medicine collected the HCW samples after informed consent.
    IRB: Ethics: The study was approved by the ethics committee of Albert-Ludwigs University Freiburg (#20-1271
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of SARS-CoV-2 antibodies: We used the following SARS-CoV-2 immunoglobuline G (IgG) assays to rule out past infection in the no COVID-19 and in the vaccine cohorts: Anti-SARS-CoV-2 ELISA IgG, detecting IgG antibodies against S1 (EUROIMMUN, Lübeck,
    Anti-SARS-CoV-2 ELISA IgG, detecting IgG
    suggested: None
    S1
    suggested: None
    Germany); recomWell SARS-CoV-2 IgG detecting IgG antibodies against the nucleoprotein (N) (Mikrogen, Munich,
    SARS-CoV-2 IgG detecting IgG
    suggested: None
    Germany); ADVIA Centaur SARS-CoV-2 total antibody (COV2T) assay, detecting total antibodies against S1-RBD (Siemens, Munich, Germany); and the Elecsys Anti-SARS-CoV-2, detecting total antibodies against N (Roche, Mannheim, Germany)
    S1-RBD
    suggested: None
    Anti-SARS-CoV-2 , detecting total antibodies against N ( Roche , Mannheim , Germany)
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Data were analysed using IBM SPSS Statistics version 24 software (www.ibm.com/spss/statistics),
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    GraphPad Prism version 9 (www.graphpad.com), and MedCalc version 19 (www.medcalc.com).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    MedCalc
    suggested: (MedCalc, RRID:SCR_015044)

    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:
    Limitation for the use of such a biological assay is the functionality of the T-cell response. Even low-dose steroid treatment may interfere with IGRA testing, as has been shown for Quantiferon TB in immunocompetent children (34). We have seen in one of our patients that even short-term steroid treatment may be of relevance. The patient yielded a negative mitogen control and a negative response to SARS-CoV-2 antigen (46 and 15 mIU/ml) three weeks after vector/mRNA heterologous vaccination, but SARS-CoV-2 S1-IgG was detectable. She was on high dose steroids when blood was drawn, but not during vaccination. After stopping steroid treatment, we repeated the assay and detected 985 mIU/ml after antigen stimulation with high positive mitogen control (1880 mIU/ml). Further, the interpretation of grey-zone results is always difficult, so we developed a double cut-off strategy including BLANK results in result interpretation. Diagnostic test accuracy analysis showed best accuracy with similar negative predictive values using our adopted cut-off strategy. In conclusion, the EUROIMMUN IGRA is an easy to perform assay for the detection of specific T-cell response against SARS-CoV-2 spike antigen. The assay is highly specific and sensitive. During a performance evaluation of the assay we were able to show that patients on immunosuppressive regimens may have isolated T-cell or antibody response or in several cases do not respond at all. For clinical practice, we recommend asking for steroi...

    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.

    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 10.1101/2021.07.17.21260316 on medRxiv