Predictors for insufficient SARS-CoV-2 vaccination response upon treatment in multiple sclerosis

Background Disease-modifying therapies (DMT) for multiple sclerosis (MS) influence SARS-CoV-2 vaccination response, which might have implications for vaccination regimens in individual patients. Expanding the knowledge of predictors for an insufficient vaccination response as a surrogate for protection against severe disease courses of infection in people with MS (pwMS) under DMT is of great importance in identifying high-risk populations.Methods Cross-sectional analysis of vaccination titre and its modifiers, in a prospective real-world cohort of 386 individuals (285 pwMS and 101 healthy controls) by two independent immunoassays between October 2021 and June 2022.Findings In our cohort, no difference in vaccination antibody level was evident between healthy controls (HC) and untreated pwMS. In pwMS lymphocyte levels, times vaccinated and DMT influence SARS-CoV-2 titre following vaccination. Those treated with selective sphingosine-1-phosphate receptor modulators (S1P) showed comparable vaccination titres to untreated; higher CD8 T cell levels prior to vaccination in B cell-depleted patients resulted in increased anti-spike SARS-CoV2 antibody levels.Interpretation PwMS under DMT with anti-CD20 treatment, in particular those with decreased CD8 levels before vaccination, as well as non-selective S1P but not selective S1P are at increased risk for insufficient SARS-CoV-2 vaccination response. This argues for a close monitoring of anti-spike antibodies in order to customize individual vaccination regimens within these patients.Funding This work was supported by the German Research Foundation (DFG, CRC-TR-128 to TU, SB, and FZ).Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2023;87: Published https://doi.org/10. 1016/j.ebiom.2022. 104411

Automated summary

This study aimed to investigate the response of multiple sclerosis (MS) patients to SARS-CoV-2 vaccination after disease-modifying therapy (DMT). The findings suggest that anti-CD20 treatment, decreased CD8 levels, and non-selective S1P treatment may lead to an insufficient response to SARS-CoV-2 vaccination. Close monitoring of anti-spike antibodies is recommended to customize vaccination regimens for these patients.