Single-Dilution COVID-19 Antibody Test with Qualitative and Quantitative Readouts

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Abstract

Serological surveillance has become an important public health tool during the COVID-19 pandemic. Detection of protective antibodies and seroconversion after SARS-CoV-2 infection or vaccination can help guide patient care plans and public health policies.

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  1. SciScore for 10.1101/2020.09.10.20192187: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Patient Cohorts: Protocol approvals for patient sample acquisition were obtained by the Institutional Review Boards (IRB) of the Albert Einstein College of Medicine (Conv, Hosp, Ctrl cohorts, US samples in hCoV cohort) or Umeå University Hospital (Swedish samples in hCoV cohort).
    IACUC: Samples were handled under BSL-2 containment in accordance with a protocol approved by the Einstein institutional biosafety committee.
    RandomizationWe evaluated our nonlinear model by 10-fold cross-validation, where the original dataset is randomly partitioned into 10 equal size subsets, and one of the subsets serves as the testing set while the remaining nine subsets are used for training the non-linear model.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Prior to analysis for anti-spike IgG and IgA antibodies, samples were heat-inactivated for 30 minutes at 56°C and stored at 4°C.
    anti-spike IgG
    suggested: None
    IgA
    suggested: None
    Plates were incubated for 1h at 25°C with 25 µl of secondary antibody (1:3,000 in 1% milk PBS-T): goat anti-human IgGHorseradish peroxidase (HRP) produced in goat (Invitrogen, Carlsbad, CA #31410) or anti-human IgA-HRP produced in goat (Millipore Sigma #A0295).
    anti-human IgGHorseradish
    suggested: None
    anti-human IgA-HRP
    suggested: (SouthernBiotech Cat# 2050-05, RRID:AB_2687526)
    Software and Algorithms
    SentencesResources
    Non-linear regression was performed using the scipy library (54).
    scipy
    suggested: (SciPy, RRID:SCR_008058)

    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:
    Although the failure of the IgG test to detect spike-specific antibodies above threshold in ~10% of COVID-19 convalescents (at an average of 28 days post-symptom onset) may arise in part from technical limitations, it likely also reflects meaningful biological heterogeneity in the antibody response to natural infection (17, 42, 43). Our positive Conv cohort was composed solely of individuals characterized as having mild disease, with none requiring oxygen support. Recent work has shown that such individuals are more likely to seroconvert slowly and to have a lower overall antibody response (15, 19, 44–46). The IgA test was considerably less sensitive (~70%) than the IgG at a threshold selected to provide 99% specificity (Fig 3a, c) in contrast to early reports of anti-S IgA assay that had higher sensitivity, but lower specificity than IgG (15, 19, 22, 25, 47). This is unlikely to be due to the delayed development of an IgA response relative to IgG, as the kinetics of IgA seroconversion has been shown to resemble, or even slightly precede that of IgG (15, 25). Rather, it may reflect the more rapid waning of serum IgA in convalescents (27). Concordantly, the IgA test appeared to detect a SARS-CoV-2 response in a higher percentage of samples from our small cohort of hospitalized patients (Fig 5). We also examined the possibility that, despite its lower sensitivity, the IgA test could be used to identify positives missed by the IgG test. We found that only 1% of the Conv cohort w...

    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.

    About SciScore

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