Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma

  1. Roxie C Girardin
  2. Alan P Dupuis
  3. Anne F Payne
  4. Timothy J Sullivan
  5. Donna Strauss
  6. Monica M Parker
  7. Kathleen A McDonough

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Abstract

Background

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) received an Emergency Use Authorization by the US Food and Drug Administration (FDA). CCP with a signal-to-cutoff ratio of ≥12 using the Ortho VITROS severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) test (OVSARS2IgG) is permitted to be labeled “high titer.” Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2.

Methods

Nine hundred eighty-one samples from 196 repeat CCP donors 0–119 days post–initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations was evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy.

Results

Of donations, 32.7%/79.5% (PRNT90/PRNT50) met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cutoff ≥85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of ≥1:640 (PRNT50) and/or ≥1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cutoff.

Conclusions

This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.04.20206011: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Testing at the Wadsworth Center was done under protocol 20-021 with approval from the NYSDOH Institutional Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The laboratorians completing the OVSARS2IgG were blinded to clinical information on the specimens, including age, gender, SARS-CoV-2 antibody test results from the Wadsworth Center clinical assay, PRNT results, and date of collection.
    SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Confluent Vero E6 cells (C1008, ATCC CRL-1586) seeded in 6 well plates were inoculated with 100 ul of the virus:serum mixture and adsorption proceeded for one hour at 37°C in 5% CO2.
    Vero E6
    suggested: None

    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.

    About SciScore

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  2. Version published to 10.1093/infdis/jiaa803
  3. Version published to 10.1101/2020.10.04.20206011v1 on medRxiv