Antibody Responses to SARS-CoV-2 Infection—Comparative Determination of Seroprevalence in Two High-Throughput Assays versus a Sensitive Spike Protein ELISA

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Abstract

Robust assay development for SARS-CoV-2 serological testing requires assessment of asymptomatic and non-hospitalised individuals to determine if assays are sensitive to mild antibody responses. Our study evaluated the performance characteristics of two high-throughput SARS-CoV-2 IgG nucleocapsid assays (Abbott Architect and Roche) and The Binding Site (TBS) Anti-Spike IgG/A/M ELISA kit in samples from healthcare workers (HCWs). The 252 samples were collected from multi-site NHS trusts and analysed for SARS-CoV-2 serology. Assay performance was evaluated between these three platforms and ROC curves were used to redefine the Abbott threshold. Concordance between Abbott and TBS was 66%. Any discrepant results were analysed using Roche, which showed 100% concordance with TBS. Analysis conducted in HCWs within 58 days post-PCR result demonstrated 100% sensitivity for both Abbott and Roche. Longitudinal analysis for >100 days post-PCR led to sensitivity of 77.2% and 100% for Abbott and Roche, respectively. A redefined Abbott threshold (0.64) increased sensitivity to 90%, producing results comparable to TBS and Roche. The manufacturer’s threshold set by Abbott contributes to lower sensitivity and elevated false-negative occurrences. Abbott performance improved upon re-optimisation of the cut-off threshold. Our findings provided evidence that TBS can be used as bespoke alternative for SARS-CoV-2 serology analysis where high-throughput platforms are not feasible on site.

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  1. SciScore for 10.1101/2021.03.19.21253518: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: At PHU, this study was approved by Portsmouth Hospital NHS Trust Research Ethics Committee.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 assays: Samples from PHU were initially analysed for SARS-CoV-2 antibodies at the Department of Medical Microbiology, PHU, using the Abbott nucleocapsid IgG assay [Abbott, Chicago, IL, USA] as part of the SIREN study.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Samples from RH were analysed using the Abbott nucleocapsid IgG assay [Abbott, Chicago, IL, USA] and further evaluated using the Elecsys® Anti-SARS-CoV-2 IgG nucleocapsid immunoassay [Roche, Basel, Switzerland].
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical Analysis: Analyses were performed using Graphpad Prism v9.0.1 (La Jolla, California, USA) and SPSS v27.0 (IBM Corp, Armonk, NY).
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    The present study has some limitations. Firstly, our sample sets may under-represent ethnic groups, did not comprise children and did not capture sufficient clinical metadata required for full clinical and analytical result interpretation. We propose a further study to be conducted, where along with participant’s PCR status and clinical symptoms, investigation of these immunoassays to detect responses in asymptomatic and mild cases should be evaluated to deduce the clinical sensitivity of different immunoassays. Whilst limited, the study highlights that the TBS assay showed enhanced sensitivity in detecting mild and asymptomatic antibody responses [9].

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT12345678Trial number did not resolve on clinicaltrials.gov. Is the number correct?NA


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.