Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population

  1. Sabra L. Klein
  2. Andrew Pekosz
  3. Han-Sol Park
  4. Rebecca L. Ursin
  5. Janna R. Shapiro
  6. Sarah E. Benner
  7. Kirsten Littlefield
  8. Swetha Kumar
  9. Harnish Mukesh Naik
  10. Michael J. Betenbaugh
  11. Ruchee Shrestha
  12. Annie A. Wu
  13. Robert M. Hughes
  14. Imani Burgess
  15. Patricio Caturegli
  16. Oliver Laeyendecker
  17. Thomas C. Quinn
  18. David Sullivan
  19. Shmuel Shoham
  20. Andrew D. Redd
  21. Evan M. Bloch
  22. Arturo Casadevall
  23. Aaron A.R. Tobian

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Abstract

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  1. Version published to 10.1172/jci142004
  2. ScreenIT

    SciScore for 10.1101/2020.06.26.20139063: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Eligible subjects were enrolled in the study under full informed consent; following consent, ∼25 mL of whole blood was collected in ACD tubes.
    IRB: The Johns Hopkins University School of Medicine Institutional Review Board reviewed and approved the sample collection and overall study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Recombinant protein expression: HEK293.2sus cells (ATCC) were obtained and adapted to Freestyle™ F-17 medium (Thermo Fisher Scientific) and BalanCD® (Irvine Scientific) using polycarbonate shake flasks (Fisherbrand) with 4mM GlutaMAX supplementation (Thermo Fisher Scientific).
    HEK293.2sus
    suggested: ATCC Cat# CRL-1573.3, RRID:CVCL_4W07)
    Viruses and cells: Vero-E6 cells (ATCC CRL-1586) and Vero-E6-TMPRSS2 cells (24) were cultured in Dulbecco’s modified Eagle medium (DMEMD) containing 10% fetal bovine serum (Gibco), 1 mM glutamine (Invitrogen), 1 mM sodium pyruvate (Invitrogen), 100 U/ml of penicillin (Invitrogen), and 100 μg/ml of streptomycin (Invitrogen) (complete media or CM).
    Vero-E6
    suggested: None
    Vero-E6-TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    The infectious virus titer was determined on Vero cells using a 50% tissue culture infectious dose (TCID50) assay as previously described for SARS-CoV (25, 26).
    Vero
    suggested: None

    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:
    There are limitations associated with this study. The samples were cross-sectional with a relatively tight window of collection. Therefore, the kinetics of the complete antibody response over time could not be determined, and it was difficult to assess how the time relative to the initial diagnosis correlates with the overall titer. The sampled population, however, represented a clinically diverse population with a wide age range that is representative of the blood donor population. The study was also limited by the lack of measurement of non-direct measures of antibody function (e.g., phagocytosis, antibody-dependent cellular cytotoxicity), but the importance of these mechanisms is not known. Initially, the FDA recommended that convalescent plasma donors would optimally have ELISA titers exceeding 1:320; this was subsequently lowered given concerns that insufficient donors would attain this threshold (15). Currently, the FDA recommends a NT concentration of >160, yet allow for a lower titer (1:80) if an alternative is unavailable (22). The FDA, however, has not been prescriptive about the assays used to derive these titer levels despite the potential variability by assay. Data from the Expanded Access Program and clinical trials are urgently needed to interpret the titers with respect to that clinical outcomes and prevention. These results provide a roadmap to select individuals who are likely to have high levels of neutralizing and anti-SARS-CoV-2 IgG antibodies to be prefe...

    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.

  3. Version published to 10.1101/2020.06.26.20139063v1 on medRxiv