SARS‐CoV ‐2 antibody persistence in COVID ‐19 convalescent plasma donors: Dependency on assay format and applicability to serosurveillance

  1. Clara Di Germanio
  2. Graham Simmons
  3. Kathleen Kelly
  4. Rachel Martinelli
  5. Orsolya Darst
  6. Mahzad Azimpouran
  7. Mars Stone
  8. Kelsey Hazegh
  9. Eduard Grebe
  10. Shuting Zhang
  11. Peijun Ma
  12. Marek Orzechowski
  13. James E. Gomez
  14. Jonathan Livny
  15. Deborah T. Hung
  16. Ralph Vassallo
  17. Michael P. Busch
  18. Larry J. Dumont

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Abstract

Background

Antibody response duration following severe acute respiratory syndrome coronavirus 2 infection tends to be variable and depends on severity of disease and method of detection.

Study design and methods

COVID‐19 convalescent plasma from 18 donors was collected longitudinally for a maximum of 63–129 days following resolution of symptoms. All the samples were initially screened by the Ortho total Ig test to confirm positivity and subsequently tested with seven additional direct sandwich or indirect binding assays (Ortho, Roche, Abbott, Broad Institute) directed against a variety of antigen targets (S1, receptor binding domain, and nucleocapsid [NC]), along with two neutralization assays (Broad Institute live virus PRNT and Vitalant Research Institute [VRI] Pseudovirus reporter viral particle neutralization [RVPN]).

Results

The direct detection assays (Ortho total Ig total and Roche total Ig) showed increasing levels of antibodies over the time period, in contrast to the indirect IgG assays that showed a decline. Neutralization assays also demonstrated declining responses; the VRI RVPN pseudovirus had a greater rate of decline than the Broad PRNT live virus assay.

Discussion

These data show that in addition to variable individual responses and associations with disease severity, the detection assay chosen contributes to the heterogeneous results in antibody stability over time. Depending on the scope of the research, one assay may be preferable over another. For serosurveillance studies, direct, double Ag‐sandwich assays appear to be the best choice due to their stability; in particular, algorithms that include both S1‐ and NC‐based assays can help reduce the rate of false‐positivity and discriminate between natural infection and vaccine‐derived seroreactivity.

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  1. Version published to 10.1111/trf.16555
  2. ScreenIT

    SciScore for 10.1101/2021.03.24.21254260: (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: 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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  3. Version published to 10.1101/2021.03.24.21254260 on medRxiv