Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID‐19 convalescent plasma clinical trial

  1. M. L. L. Madariaga
  2. J. J. Guthmiller
  3. S. Schrantz
  4. M. O. Jansen
  5. C. Christensen
  6. M. Kumar
  7. M. Prochaska
  8. G. Wool
  9. A. Durkin‐Celauro
  10. W. H. Oh
  11. L. Trockman
  12. J. Vigneswaran
  13. R. Keskey
  14. D. G. Shaw
  15. H. Dugan
  16. N.‐Y. Zheng
  17. M. Cobb
  18. H. Utset
  19. J. Wang
  20. O. Stovicek
  21. C. Bethel
  22. S. Matushek
  23. M. Giurcanu
  24. K. G. Beavis
  25. D. di Sabato
  26. D. Meltzer
  27. M. K. Ferguson
  28. J. P. Kress
  29. K. Shanmugarajah
  30. J. B. Matthews
  31. J. F. Fung
  32. P. C. Wilson
  33. J. C. Alverdy
  34. J. S. Donington

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Abstract

Background

Convalescent plasma therapy for COVID‐19 relies on transfer of anti‐viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID‐19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial.

Methods

Multivariable analysis of clinical and serological parameters in 103 confirmed COVID‐19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed‐effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID‐19.

Results

Donor antibody titres ranged from 0 to 1 : 3892 (anti‐receptor binding domain (RBD)) and 0 to 1 : 3289 (anti‐spike). Higher anti‐RBD and anti‐spike titres were associated with increased age, hospitalization for COVID‐19, fever and absence of myalgia (all P  < 0.05). Fatigue was significantly associated with anti‐RBD ( P  = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti‐RBD and anti‐spike than O donors ( P  < 0.05). No toxicity was associated with plasma transfusion. Non‐ECMO recipient anti‐RBD antibody titre increased on average 31% per day during the first three days post‐transfusion ( P  = 0.01) and anti‐spike antibody titre by 40.3% ( P  = 0.02).

Conclusion

Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID‐19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post‐transfusion. A more complete understanding of the dose‐response effect of plasma transfusion amongst COVID‐19‐infected patients is needed.

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  1. Version published to 10.1111/joim.13185
  2. ScreenIT

    SciScore for 10.1101/2020.06.21.20132944: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: One surgeon visited the hospital COVID-19 unit daily to obtain consent and research samples.
    IRB: Study approval: This study was approved by the Institutional Review Board (IRB20-0523).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody Test and Real-Time Polymerase Chain Reaction (RT-PCR) Detection of SARS-CoV-2 Levels of anti-RBD and anti-spike antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in blood samples at time of donation and plasma recipients, as previously described (17).
    Real-Time Polymerase Chain Reaction (RT-PCR
    suggested: None
    anti-RBD
    suggested: None
    anti-spike
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistics: Study data were collected and managed using REDCap electronic data capture tools hosted at UCM (18, 19).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Data analysis was conducted within Rstudio environment, and R markdown files with fully reproducible data analysis can be obtained from the authors upon request.
    Rstudio
    suggested: (RStudio, RRID:SCR_000432)

    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
    NCT04340050CompletedCOVID-19 Convalescent Plasma

    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.

  3. Version published to 10.1101/2020.06.21.20132944v1 on medRxiv