Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs

Background: Little is known about COVID-19 course and outcomes after a third booster dose ofmRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treatedwith ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response tomRNA-vax.Objectives: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCRand FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab(NTZ).Methods: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNAVax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use.Results: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included.Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment durationwere significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared withthose on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%,respectively). Regression models showed that the majority of the differences observed were not related tothe disease-modifying treatments (DMTs) used. No fatal cases were observed.Conclusion: Our results support the effectiveness of the third booster dose of mRNA-Vax against severeforms of COVID-19 in pwMS treated with OCR and FNG.