Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

  1. Stephan Winklmeier
  2. Katharina Eisenhut
  3. Damla Taskin
  4. Heike Rübsamen
  5. Ramona Gerhards
  6. Celine Schneider
  7. Paul R. Wratil
  8. Marcel Stern
  9. Peter Eichhorn
  10. Oliver T. Keppler
  11. Matthias Klein
  12. Simone Mader
  13. Tania Kümpfel
  14. Edgar Meinl

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Abstract

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  1. Version published to 10.1016/j.isci.2021.103659
  2. ScreenIT

    SciScore for 10.1101/2021.05.15.21257210: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study approval: The study was approved by the ethical committee of the medical faculty of the Ludwig-Maximilians-Universität Munich.
    Consent: Written informed consent was obtained from each donor prior to their inclusion in the study.
    Sex as a biological variableAs a reference, we analyzed pre-pandemic blood samples from six healthy adults (HC), two males and four females, with a mean age of 28 years.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    All study participants tested positive for SARS-CoV-2 antibodies at least once after they were infected.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    The total B-cell frequency was measured by flow cytometry using the anti-human CD19-PerCP-Cy5.5 Ab (SJ25C1; eBioscience, San Diego, CA, USA), and analysis was performed using FlowJo (10.7.1, BD, Franklin Lakes, NJ, USA).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistics: Statistical analyses were performed using GraphPad Prism 7 (GraphPad Software Inc.,
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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: We detected the following sentences addressing limitations in the study:
    Our study had some limitations. The observation of patients was performed up to 8 months after infection. Longer observation times are necessary to learn more about features of B cell persistence. Two donors, who lost SARS-CoV-2-specific IgG but maintained specific memory B cells received immunosuppressive treatment (canakinumab plus hydroxychloroquine or dimethyfumarate) at the time of blood sampling for this study. The impact of immunomodulatory therapies on the maintenance of IgG and memory B cells after infection or vaccination has yet to be analyzed in detail. We analyzed the persistence of B cells reactive to the S1 protein, but the maintenance of B cells against other SARS-CoV-2 proteins remains to be analyzed; although the response to the RBD is of paramount importance, as the RBD is targeted by neutralizing Abs (3). We analyzed circulating memory B cells but are aware that both systemic and mucosal immunity are relevant for protection. We did not analyze the persistence of B cells in patients very severely affected by COVID-19, but it has been reported that the serum Ig response is even greater and longer-lasting in these patients (6, 13). In this study, we showed that circulating IgG memory B cells specific for SARS-CoV-2 persist in the blood after infection despite the loss of systemic IgG. These persisting B cells can be harnessed to identify a previous infection. Furthermore, these B cells gave rise to neutralizing Abs and showed high cross-reactivity against the...

    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

    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 10.1101/2021.05.15.21257210v1 on medRxiv