Potential Biases Arising From Epidemic Dynamics in Observational Seroprotection Studies

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Abstract

The extent and duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods for alleviating biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated. Here, we show how geographic structure and the underlying, natural dynamics of epidemics can also induce noncausal associations. We take the approach of simulating serological studies in the context of an uncontrolled or controlled epidemic, under different assumptions about whether prior infection does or does not protect an individual against subsequent infection, and using various designs and analytical approaches to analyze the simulated data. We find that in studies assessing whether seropositivity confers protection against future infection, comparing seropositive persons with seronegative persons with similar time-dependent patterns of exposure to infection by stratifying or matching on geographic location and time of enrollment is essential in order to prevent bias.

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  1. SciScore for 10.1101/2020.05.02.20088765: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: Thank you for sharing your code.


    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.

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