Evaluation of serological tests for detecting SARS-CoV-2 antibodies: implementation in assessing post vaccination status

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Abstract

Background

The anti-SARS-CoV-2 immunological assays have promising applications in the control and surveillance of the current COVID-19 pandemic. Therefore, large number of serological assays are developed in the commercial market to measure SARS-CoV-2 antibodies, which requires evaluation before their application in large scale.

Objectives

To evaluate the performances of commercially available serological assays for detecting SARS-CoV-2 antibodies.

Methods

The study compared the performances of six different methods for detection of antibodies against SARS-CoV-2 which includes (i) Genscript SARS-CoV-2 surrogate virus neutralization test kit [Test A] (ii) Diasorin - SARS-CoV-2 S1/S2 IgG detection [Test B] (iii) Alinity SARS-CoV-2 IgG II [Test C] (iv) Diasorin – SARS-CoV-2 TrimericS IgG [Test D] (v) Roche Elecsys Anti-SARS-CoV-2 – cobas [Test E] (vi) AESKULISA (AESKU Enzyme Linked Immunosorbent Assay) [Test F] against the gold standard Plaque Reduction Neutralization Test (PRNT).

Results

Test E had the highest sensitivity and Test A had the highest specificity The ROC for tests A, C, D and E showed optimum cut-offs that differed from the manufacturer’s recommendation. Test D had the best performance considering all the performance indicators with the highest agreement with the PRNT results. Parallel testing of test A with test D and test B had the optimum performance.

Conclusion

Serological assays that are commercially available are very promising and show good agreement with the standard PRNT results. Studies on large samples for optimization of the assay cut-off values and cost-effective evaluations on parallel testing methods are needed to make recommendations on these commercial assays.

Importance

Serological assays that are commercially available are very promising and this paper adds new knowledge about the optimization of these kits for evaluating post vaccination antibodies status. It highlights the positive and negative aspects of each of these assays in terms of sensitivity, specificity, positive and negative predictive values, and the agreement of results with the standard neutralization test. When serological assays are being used to assess post-vaccine immune status, a balance of all parameters needs to be considered rather than emphasizing only on high specificity. This is particularly relevant in the current situation where vaccination is happening around the globe, high sensitivity assays will result in reporting a lower percentage of false negative reports and avoids panic about lack of vaccine response. It is important that we understand the strengths and limitations of commercially available serological assays for better application of these tests to understand immune response and the duration of protection post vaccination.

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  1. SciScore for 10.1101/2021.04.27.21256205: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The six different methods are (i) Genscript SARS-CoV-2 surrogate virus neutralization test kit [Test A] (ii) Diasorin - SARS-CoV-2 S1/S2 IgG detection [Test B] (iii) Alinity SARS-CoV-2 IgG II [Test C] (iv) Diasorin – SARS-CoV-2 TrimericS IgG [Test D] (v) Roche Elecsys Anti-SARS-CoV-2 – cobas [Test E] (vi) AESKULISA (AESKU Enzyme Linked Immunosorbent Assay) [Test F] The PRNT is a serological test which utilizes the ability of a specific antibody to neutralize a virus, in turn, preventing the virus from causing the formation of plaques in a cell monolayer.
    Anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    In this study, Vero E6 cells were grown to a confluent monolayer in a 6 well plate.
    Vero E6
    suggested: RRID:CVCL_XD71)

    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.

    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.