Fluctuating High Throughput Serological Assay Results in Recurrent Convalescent Plasma Donors

  1. Larry L. Luchsinger
  2. Shiraz Rehmani
  3. Andrew Opalka
  4. Donna Strauss
  5. Christopher D. Hillyer
  6. Patricia Shi
  7. Bruce S. Sachais

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Abstract

The clinical and scientific communities rely on serology testing to analyze the degree of antibody-mediated immunity afforded to recovered patients from SARS-CoV-2 infection. Neutralizing antibodies present in COVID-19 convalescent plasma (CCP) remains a practical therapy to treat COVID-19 patients requiring hospitalization. However, it remains unclear how long antibody levels persist in CCP donors after recovery. An accurate estimation of antibody kinetics in CCP donors provide an important observation to further define the extent of long-term immunity in recovered patient and simultaneously inform CCP collection processes in efforts to improve CCP dosing and therapeutic outcome. In this study, we analyzed 63 donors and measured antibody levels using two high throughput screening assays (HTSA) designed to detect antibodies targeting the spike protein (S1) and nucleocapsid protein (NP) of SARS-CoV-2 and monitored antibody levels between 2-8 consecutive donations. We show that anti-S1 antibody levels, as measured using the Ortho Total Ig HTSA, increased over time in repeat CCP donors while anti-NP antibody levels, as measured using the Abbott IgG HTSA, were unchanged or decreased over time. When we normalized these data, we found that both the absolute levels of anti-S1 antibodies and the ratio between S1 and NP antibodies tends to increase over time. These data have important implications for the convalescent donation process, patient protection from future infection and characterization of the SARS-CoV-2 immune response.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.25.20219147: (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

    Antibodies
    SentencesResources
    Thereafter, donors could donate CCP following the standard 28-day donation interval for plasma as long as appropriate anti-SARS-CoV2 antibodies continued to demonstrate.
    anti-SARS-CoV2
    suggested: None
    Software and Algorithms
    SentencesResources
    Donor blood samples were tested using the Ortho VITROS™ SARS-CoV-2 Total Ig assay and the Abbott SARS-CoV-2 IgG assay.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    High-throughput Serology Assays: Samples were analyzed using the Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay using the Abbott Architect i2000SR (Abbott Core Laboratories), as well as the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Test using the VITROS 5600 (Ortho Clinical Diagnostics).
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)

    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:
    While our study provides an intriguing analysis of antibody responses over time in convalescent plasma donors, we recognize some limitations. First, our sample size was considerable but not large enough to make generalizations about specific demographics. Further, our longitudinal analysis of recurring CP donors is limited to 45 days from the first donation. Therefore, future studies designed to monitor antibody levels over a longer time period in different age groups, ethnic backgrounds and between genders for extended periods of time are required. Finally, our longitudinal analysis of serological results are somewhat consistent with the recent report by Muechsch et al. where the authors used a variety of HTSA assays.(17) Indeed, both of our studies included that the Abbott IgG assay showed a decline in anti-NP antibodies with time and some anti-S1 assays showed increase over time. However, Muechsch et al. concluded that neutralizing activity in a random group of blood donors decreased between 20-80 days post-diagnosis. However, the minimal level of neutralizing activity or serology value needed to confer effective CP therapy in transfusion recipients or serum antibody levels to prevent reinfection remains to be determined.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.10.25.20219147 on medRxiv