Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis

  1. Tatjana Schwarz
  2. Carolin Otto
  3. Terry C Jones
  4. Florence Pache
  5. Patrick Schindler
  6. Moritz Niederschweiberer
  7. Felix A Schmidt
  8. Christian Drosten
  9. Victor M Corman
  10. Klemens Ruprecht

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Abstract

Optimal management of anti-CD20-treated patients with multiple sclerosis (pwMS) is an important clinical task during the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic.

Objectives:

To characterize humoral and cellular immune responses to SARS-CoV-2 vaccinations/infections in a longitudinal cohort of anti-CD20 treated ( n = 175) and anti-CD20 therapy-naïve ( n = 41) pwMS.

Methods:

Anti-SARS-CoV-2 spike protein immunoglobulin G (IgG) and IgA, virus neutralizing capacity, IgG avidity and SARS-CoV-2-specific T cells were determined.

Results:

Following two SARS-CoV-2 vaccinations, not only SARS-CoV-2 spike protein IgG and IgA, but also neutralizing capacity and avidity of SARS-CoV-2 IgG were lower in anti-CD20-treated ( n = 51) than in anti-CD20 therapy-naïve pwMS ( n = 14) and in healthy controls (HC, n = 19). However, in all anti-CD20-treated pwMS vaccinated twice ( n = 26) or infected with SARS-CoV-2 ( n = 2), in whom SARS-CoV-2-specific T cells were measured, SARS-CoV-2-specific T cells were detectable, at levels similar to those of twice-vaccinated anti-CD20 therapy-naïve pwMS ( n = 7) and HC ( n = 19). SARS-CoV-2-S1 IgG levels ( r = 0.42, p = 0.002), antibody avidity ( r = 0.7, p < 0.001), and neutralizing capacity ( r = 0.44, p = 0.03) increased with time between anti-CD20 infusion and second vaccination. Based on detection of SARS-CoV-2 antibodies, SARS-CoV-2 infections occurred in 4 out of 175 (2.3%) anti-CD20-treated pwMS, all of whom recovered fully.

Conclusions:

These findings should inform treatment decisions and SARS-CoV-2 vaccination management in pwMS.

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  1. Version published to 10.1177/13524585221094478
  2. ScreenIT

    SciScore for 10.1101/2021.10.11.21264694: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical approval: The study was approved by the ethical committee of Charité - Universitätsmedizin Berlin (EA2/152/21 and EA1/068/20).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 specific humoral and cellular immune responses: To detect anti-SARS-CoV-2 antibodies, a SARS-CoV-2 spike subunit 1 (S1) IgG and IgA ELISA Kit (Euroimmun, Lübeck, Germany) were used.
    spike subunit 1 (S1) IgG
    suggested: None
    17 To confirm results obtained by ELISA, a recombinant anti-SARS-CoV-2 spike immunofluorescence test (IFT)18 and a microarray-based multiparametric immunoassay for detection of IgG antibodies against spike and nucleocapsid protein (SeraSpot®Anti-SARS-CoV-2 IgG, Seramun Diagnostica GmbH, Heidesee, Germany) were applied.17,19 The neutralizing capacity of SARS-CoV-2 antibodies was analyzed by a plaque reduction neutralization test (PRNT), using authentic SARS-CoV-2.18,20 IgG avidity maturation was determined by a modified SARS-CoV-2 S1 ELISA (Euroimmun).
    anti-SARS-CoV-2
    suggested: None
    SeraSpot®Anti-SARS-CoV-2 IgG
    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:
    Limitations: Limitations of this observational study include lack of data on total lymphocyte and B cell counts at the time of SARS-CoV-2 vaccinations/infections precluding evaluations of these parameters as potential risk factors for low vaccine immunogenicity. Furthermore, given the limited follow-up time of the present study and potentially decreasing SARS-CoV-2 immune responses over time, it will be important to analyse anti-SARS-CoV-2 antibody and T cell responses in anti-CD20 treated patients also in the long term. Finally, the low numbers of pwMS vaccinated with vaccines other than BNT162b2 precluded formal comparisons of immunogenicity of different vaccines.

    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 10.1101/2021.10.11.21264694v2 on medRxiv
  4. Version published to 10.1101/2021.10.11.21264694v1 on medRxiv