Patients treated with anti-CD20 therapy can mount robust T cell responses to mRNA-based COVID-19 vaccines

  1. Natacha Madelon
  2. Kim Lauper
  3. Gautier Breville
  4. Irène Sabater Royo
  5. Rachel Goldstein
  6. Diego O. Andrey
  7. Alba Grifoni
  8. Alessandro Sette
  9. Claire-Anne Siegrist
  10. Axel Finckh
  11. Patrice H. Lalive
  12. Arnaud M. Didierlaurent
  13. Christiane S. Eberhardt

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Abstract

Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. This study assesses humoral and T-cell responses to mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 + T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). Vaccine-specific CD4 + and CD8 + T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the prevention of severe COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.21.21260928: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study approval: This prospective observational study was conducted at the Geneva University Hospitals (HUG), Switzerland according to the principles of Good Clinical Practice and was approved by the Geneva Cantonal Ethics Commission (2021-00430).
    Consent: Informed consent was obtained from all participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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 of our study include the small sample size and the short follow-up after vaccination. We also were not able to correlate T cell findings with clinical protection as the study was not designed to measure efficacy, which is pivotal in the identification of vaccine-responders and the indication for a potential third vaccine dose. Strengths of our study is the prospective design and the ability to evaluate two patient populations under anti-CD20 therapy who have different underlying conditions that do both not greatly affect other axes of immune responses, such as in poly-immunosuppressed patients, or those suffering from lymphoma or leukemia. In summary, our study suggests that patients with anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines similar to immunocompetent controls. Although patients treated with anti-CD20 treatment have decreased humoral responses to mRNA COVID-19 vaccines, elicited T-cell memory response could reduce complications of SARS-CoV-2 infection in this vulnerable population.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 15. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  2. Version published to 10.1101/2021.07.21.21260928v1 on medRxiv