Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals

  1. Alena J. Markmann
  2. Natasa Giallourou
  3. D. Ryan Bhowmik
  4. Yixuan J. Hou
  5. Aaron Lerner
  6. David R. Martinez
  7. Lakshmanane Premkumar
  8. Heather Root
  9. David van Duin
  10. Sonia Napravnik
  11. Stephen D. Graham
  12. Quique Guerra
  13. Rajendra Raut
  14. Christos J. Petropoulos
  15. Terri Wrin
  16. Caleb Cornaby
  17. John Schmitz
  18. JoAnn Kuruc
  19. Susan Weiss
  20. Yara Park
  21. Ralph Baric
  22. Aravinda M. de Silva
  23. David M. Margolis
  24. Luther A. Bartelt

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Abstract

In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex.

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  1. Version published to 10.1128/msphere.00275-21
  2. ScreenIT

    SciScore for 10.1101/2021.02.01.21250493: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All donors who participated provided written informed consent.
    IRB: The research was approved by the UNC Institutional Review Board, and conducted under good clinical research practices.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Bound IgG was detected via addition of anti-human acridinium-labeled second-step antibody.
    anti-human acridinium-labeled second-step
    suggested: None
    SARS-CoV-2 Pseudovirus neutralization assay: The “PhenoSense SARS CoV-2 nAb Assay” has been developed by leveraging the proprietary PhenoSense Assay platform that was developed to evaluate antiretroviral drug susceptibility(39) and later adapted to evaluate entry inhibitors and neutralizing antibody(40) as well as co-receptor tropism(41).
    antibody(40
    suggested: None
    The expression of luciferase activity in target cells is inhibited in the presence of anti-SARS CoV-2 neutralizing antibody.
    anti-SARS CoV-2 neutralizing antibody.
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, Vero E6 cells were infected with SARS-2-pLuc viruses and titered to generate an 8-point curve.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Nucleocapsid protein ELISA: Detection of IgG antibody to SARS-CoV-2 N antigen was performed with a microparticle chemiluminescence assay (Abbott Laboratories) on the Abbott Architect i2000SR immunoassay analyzer.
    Abbott Laboratories
    suggested: None
    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:
    One major limitation of this study is the demographic uniformity of our study population, which limits the generalizability of our findings and highlights the need to do these studies with a more diverse and representative population. Another bias in our donor population is our focus on re-calling donors with higher neutralizing antibody titers to repeat donations. Thus, our “sequential donation” population is biased towards higher titer donors. Understanding human antibody responses and correlates of neutralizing antibodies to SARS-CoV-2 is critical in the next coming phase of understanding SARS-CoV-2 vaccine efficacy and protection against reinfection. We find that WT SARS-CoV-2 functionally neutralizing antibodies are maintained for months after infection. Our findings further support the role of RBD binding antibodies as correlates of functionally neutralizing antibodies, suggesting that vaccines that induce potent RBD responses may be particularly efficacious. Furthermore, we identify for the first time, a role for sex differences as sustained correlates of WT SARS-CoV-2 functional neutralization. The association of male sex in this cohort with higher neutralizing antibody levels reveals a sexual dimorphism in humoral immune responses to SARS-CoV-2. We hypothesize that this is likely due to a combination of factors such as differences in duration of mucosal replication, T cell responses, sex hormone roles in immune activation, and genetic differences in immune responses....

    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 10.1101/2021.02.01.21250493v1 on medRxiv