COVID ‐19 Vaccine Response in People with Multiple Sclerosis

  1. Emma C. Tallantyre
  2. Nicola Vickaryous
  3. Valerie Anderson
  4. Aliye Nazli Asardag
  5. David Baker
  6. Jonathan Bestwick
  7. Kath Bramhall
  8. Randy Chance
  9. Nikos Evangelou
  10. Katila George
  11. Gavin Giovannoni
  12. Andrew Godkin
  13. Leanne Grant
  14. Katharine E. Harding
  15. Aimee Hibbert
  16. Gillian Ingram
  17. Meleri Jones
  18. Angray S. Kang
  19. Samantha Loveless
  20. Stuart J. Moat
  21. Neil P. Robertson
  22. Klaus Schmierer
  23. Martin J. Scurr
  24. Sita Navin Shah
  25. Jessica Simmons
  26. Matthew Upcott
  27. Mark Willis
  28. Stephen Jolles
  29. Ruth Dobson

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Abstract

The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines in people with multiple sclerosis (MS).

Methods

Four hundred seventy‐three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID‐19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS‐CoV‐2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS‐CoV‐2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response.

Results

Compared to no disease modifying therapy, the use of anti‐CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01–0.06, p  < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01–0.12) were associated with lower seroconversion following the SARS‐CoV‐2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti‐CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti‐CD20 medications. Preliminary data on cellular T‐cell immunity showed 40% of seronegative subjects had measurable anti‐SARS‐CoV‐2 T cell responses.

Interpretation

Some disease modifying therapies convey risk of attenuated serological response to SARS‐CoV‐2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 20219999:n/a–n/a

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  1. Version published to 10.1002/ana.26251
  2. ScreenIT

    SciScore for 10.1101/2021.07.31.21261326: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written informed consent to take part in this study.
    IRB: This study has Research Ethics Committee approval (REC 19/WA/0058 (Wales REC 3 – covering samples processed in Cardiff), 05/WSE03/111 (South East Wales REC – covering samples processed in Cardiff) and 20/NE/0176 (Newcastle North Tyneside REC – covering QMUL samples)).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    In a series of paired plasma and dried blood spots (n=22 antibody negative and n=25 antibody positive samples) we observed good agreement between paired specimens (r=0.994) and the gradient of the slope was 1.241x.
    n=22
    suggested: (Advanced Targeting Systems Cat# AB-N22, RRID:AB_458735)
    n=25
    suggested: None
    The impact of time between last dose of anti-CD20 monoclonal antibody (ocrelizumab and rituximab, excluding ofatumamab given different administration schedule) and first vaccine dose, and odds of seroconversion, was established using univariate logistic regression.
    anti-CD20
    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:
    This is deserving of further study given potential limitations of power to address this question. Current evidence suggests that heterologous vaccine regimens may elicit stronger antibody and T-cell responses [18,19]. The effect of age on vaccine response in this cohort is in line with data from the general population [15], and may be entirely due to age-related immunosenescence [17], or there may be an additional impact from collider bias related to age, disability progression and DMT choice. This study made use of dried blood spot sampling, reducing the need for potentially vulnerable people to attend healthcare facilities during the pandemic as well as reduced costs for phlebotomist time and equipment. Dried blood spot sampling has been used since the 1960s for neonatal screening for inborn errors of metabolism [20], and has demonstrated utility across a number of medical uses [21]. Their use as a tool for serological screening of IgG levels is particularly well established [22], and the utility has been highlighted during the COVID-19 pandemic [23]. Whilst extensive work was undertaken to develop and validate the assays used in this study, the lack of gold standard for RBD assay development was a potential limitation; since a true negative result was defined based on historical samples. In order to increase the power for this study, samples were analysed in two laboratories and data pooled. The assay used in the UHW laboratory was subject to significant ceiling effects, w...

    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 10.1101/2021.07.31.21261326v1 on medRxiv