Abstract
Background and Objectives Some disease-modifying treatments impair response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in multiple sclerosis (MS), potentially increasing the risk of breakthrough infections. We aimed to investigate longitudinal SARS-CoV-2 antibody dynamics and memory B cells after 2 and 3 messenger RNA (mRNA) vaccine doses and their association with the risk of COVID-19 in patients with MS on different treatments over 1 year.
Methods Prospective observational cohort study in patients with MS undergoing SARS-CoV-2 mRNA vaccinations. Antispike (anti-S) immunoglobulin G (IgG) titers were measured by chemiluminescence microparticle immunoassay. Frequencies of spike-specific memory B cells were measured on polyclonal stimulation of peripheral blood mononuclear cells and screening of secreted antibodies by ELISA.
Results We recruited 120 patients with MS (58 on anti-CD20 antibodies, 9 on sphingosine 1-phosphate (S1P) receptor modulators, 15 on cladribine, 24 on teriflunomide (TFL), and 14 untreated) and collected 392 samples up to 10.8 months after 2 vaccine doses. When compared with untreated patients, anti-CD20 antibodies (β = −2.07, p < 0.001) and S1P modulators (β = −2.02, p < 0.001) were associated with lower anti-S IgG, while TFL and cladribine were not. Anti-S IgG decreased with months since vaccine (β = −0.14, p < 0.001), independently of treatments. Within anti-CD20 patients, anti-S IgG remained higher in those with greater baseline B-cell counts and were not influenced by postvaccine anti-CD20 infusions. Anti-S IgG increase after a 3rd vaccine was mild on anti-CD20 and S1P modulators. Spike-specific memory B-cell responses were weaker on S1P modulators and anti-CD20 than on TFL and influenced by postvaccine anti-CD20 infusions. The frequency of breakthrough infections was comparable between DMTs, but the risk of COVID-19 was predicted by the last measured anti-S IgG titer before infection (OR = 0.56, 95% CI = 0.37–0.86, p = 0.008).
Discussion Postvaccine anti-S IgG titers decrease over time regardless of MS treatment and are associated with breakthrough COVID-19. Both humoral and specific memory B-cell responses are diminished on S1P modulators. Within anti-CD20–treated patients, B-cell count at first vaccine determines anti-S IgG production, whereas postvaccine anti-CD20 infusions negatively affect spike-specific memory B cells.
Glossary
- anti-S=
- antispike;
- CLD=
- cladribine;
- DMTs=
- disease-modifying treatments;
- IgG=
- immunoglobulin G;
- mRNA=
- messenger RNA;
- MS=
- multiple sclerosis;
- PBS=
- phosphate-buffered saline;
- S1P-mod=
- sphingosine 1-phosphate receptor modulators;
- SARS-CoV-2=
- severe acute respiratory syndrome coronavirus 2;
- TFL=
- teriflunomide
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
Submitted and externally peer reviewed. The handling editor was Josep O. Dalmau, MD, PhD, FAAN.
COVID-19 Resources: NPub.org/COVID19
- Received June 8, 2022.
- Accepted in final form August 29, 2022.
- Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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