Predictive values, uncertainty, and interpretation of serology tests for the novel coronavirus

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Abstract

Antibodies testing in the coronavirus era is frequently promoted, but the underlying statistics behind their validation has come under more scrutiny in recent weeks. We provide calculations, interpretations, and plots of positive and negative predictive values under a variety of scenarios. Prevalence, sensitivity, and specificity are estimated within ranges of values from researchers and antibodies manufacturers. Illustrative examples are highlighted, and interactive plots are provided in the Supplementary Information. Implications are discussed for society overall and across diverse locations with different levels of disease burden. Specifically, the proportion of positive serology tests that are false can differ drastically from up to 3%–88% for people from different places with different proportions of infected people in the populations while the false negative rate is typically under 10%.

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  1. SciScore for 10.1101/2020.06.04.20122358: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: Thank you for sharing your code and data.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Consequences of false negative test results would likely relate to failing to remove negative effects of limitations during the pandemic. For example, assuming that antibodies indeed confirm protection, then people with antibodies who test negative would be safe to return to work but their negative test might convince them to remain at home. This would prolong the negative mental and physical effects of social isolation as well as economic effects to individuals and society overall. Fortunately, the false negative rate was under 10% in all scenarios. Unfortunately, the false positive rate can be shockingly high. Based on the prevalence estimated throughout the US and serology studies in California, New York and Boston, the FPR of antibody test results range from 2% to 88%. Point estimates of tests ests with an EUA44 reached 86% and upper limits reached 93% when the prevalence is 1%. Tests with low PPV and high FPR can be dangerous by giving patients with positive tests a false sense of security. Ironically, these people may then increase their risk of contracting Covid19 if they relax their use of protective measures, such as mask wearing and social distancing. The timing of the test may impact the result, as discussed in the supplementary material. Briefly, seroconversion is the process during which antibodies develop after infected by Covid19 become detectable in the blood; the seroconversion duration could complicate the consideration of interpretation of serology test res...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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