Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern

  1. Maggie Li
  2. Evan J. Beck
  3. Oliver Laeyendecker
  4. Yolanda Eby
  5. Aaron A. R. Tobian
  6. Patrizio Caturegli
  7. Camille Wouters
  8. Gregory R. Chiklis
  9. William Block
  10. Robert O. McKie
  11. Michael J. Joyner
  12. Timothy D. Wiltshire
  13. Allan B. Dietz
  14. Thomas J. Gniadek
  15. Arell J. Shapiro
  16. Anusha Yarava
  17. Karen Lane
  18. Daniel F. Hanley
  19. Evan M. Bloch
  20. Shmuel Shoham
  21. Edward R. Cachay
  22. Barry R. Meisenberg
  23. Moises A. Huaman
  24. Yuriko Fukuta
  25. Bela Patel
  26. Sonya L. Heath
  27. Adam C. Levine
  28. James H. Paxton
  29. Shweta Anjan
  30. Jonathan M. Gerber
  31. Kelly A. Gebo
  32. Arturo Casadevall
  33. Andrew Pekosz
  34. David J. Sullivan

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Abstract

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

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  1. Version published to 10.1182/bloodadvances.2022007410
  2. ScreenIT

    SciScore for 10.1101/2022.03.01.22271662: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Approvals were obtained from the Institutional Review Boards at Johns Hopkins University School of Medicine as single IRB for all participating sites and the Department of Defense (DoD) Human Research Protection Office.
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    : Plasma neutralizing antibodies (nAbs) were determined as described for SARS-CoV-2.1,12 WA-1 (SARS-CoV-2/USA-WA1/2020 EPI_ISL_404895) was obtained from BEI Resources while the, delta (hCoV19/USA/MD-HP05660/2021 EPI_ISL_2331507) and omicron (hCoV19/USA/MD-HP20874/2021 EPI_ISL_7160424) variants were isolated from COVID-19 patients at Johns Hopkins Hospital as previously described.
    Plasma neutralizing antibodies
    suggested: None
    Software and Algorithms
    SentencesResources
    13 The nAb titer was calculated as the highest serum dilution that eliminated the cytopathic effect in 50% of the wells (NT50) and the area under the curve (AUC) was calculated using Graphpad Prism.
    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: 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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.03.01.22271662 on medRxiv