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 10.13039/501100001659German Research Foundation (DFG, CRC-TR-128 to TU, SB, and FZ).