Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors

  1. Valeria De Giorgi
  2. Kamille A West
  3. Amanda N Henning
  4. Leonard Chen
  5. Michael R Holbrook
  6. Robin Gross
  7. Janie Liang
  8. Elena Postnikova
  9. Joni Trenbeath
  10. Sarah Pogue
  11. Tania Scinto
  12. Harvey J Alter
  13. Cathy Corny Cantilena

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Abstract

Background

Characterizing the kinetics of the antibody response to SARS□CoV□2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection.

Methods/Materials

We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA).

Results

From April to November 2020 we enrolled 202 donors, mean age 47.3 ±14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12-163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA 50 were positively associated with mean IgG levels (p = <0.0001). Mean IgG levels and neutralizing titers were positively associated with COVID-19 severity, increased donor age and BMI (p=0.0006 and p=0.0028, p=0.0083 and p=0.0363, (p=0.0008 and p=0.0018, respectively). Over the course of repeat visits, IgG decreased in 74.1% of donors; FRNA 50 decreased in 44.4% and remained unchanged in 33.3% of repeat donors. A weak negative correlation was observed between total Ab levels and number of days post-symptom recovery (r = 0.09).

Conclusion

Anti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.08.21253093: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: CCP Donor qualification and plasma collection: COVID-19 convalescent plasma donors were prospectively enrolled onto an IRB-approved protocol (Clinical Trials Number: NCT04360278) and provided written informed consent for the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableRoutine plasma donor testing was performed, including standard infectious disease testing, blood group assessment and HLA antibody testing in female donors.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 Immunoassay: Donor samples were tested for SARS-CoV-2 antibodies using the Ortho-Clinical Diagnostics VITROS® Total (IgA/G/M) and IgG COVID-19 Antibody tests following the manufacturer’s package insert instructions (https://www.fda.gov/media/136967/download).
    SARS-CoV-2
    suggested: None
    In the second stage, HRP-labeled murine monoclonal anti-human IgG antibodies (or recombinant SARS-CoV-2 spike protein S1 antigen for the total assay) are added in the conjugate reagent.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    This assay was performed by incubating a fixed volume of virus (0.5 multiplicity of infection (MOI)) with an equivalent volume of test plasma for 1 h at 37 ºC prior to adding to Vero E6 cells (BEI, Manassas, VA, USA, #NR-596) plated in 96-well plates.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    All data were analyzed using Excel.
    Excel
    suggested: None
    Statistical Analysis: All statistical analyses were performed using GraphPad Prism version 8.4.3 (www.graphpad.com).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04360278RecruitingPlasma Collection From Convalescent and/or Immunized Donors …

    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 10.1101/2021.03.08.21253093v1 on medRxiv