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

Background: Patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) or fingolimod (FNG) show weakened immune responses to SARS-CoV-2 mRNA vaccines; little is known about COVID-19 course after a third (booster) dose. Objectives: To evaluate COVID-19 course and outcomes after three mRNA vaccine doses in pwMS receiving OCR or FNG and compare them with natalizumab (NTZ). Methods: Multicentre observational study across 17 Italian MS centers including pwMS ≥18 years on stable NTZ/OCR/FNG since the first vaccine dose, with COVID-19 diagnosed ≥14 days after the booster; steroid use around vaccination or infection was an exclusion. Results: 290 pwMS (79 NTZ, 126 OCR, 85 FNG) were analyzed. Groups differed in age, EDSS, MS phenotype, and disease/treatment duration. PwMS on OCR and FNG were slightly more symptomatic and had higher hospitalization rates (11.1% OCR; 7.1% FNG; 1.3% NTZ). Regression analyses indicated most differences were attributable to demographic/clinical factors rather than DMT class. No deaths occurred. Conclusion: A third mRNA vaccine dose was associated with protection from severe COVID-19 in pwMS on OCR and FNG, supporting booster effectiveness in these populations with attenuated vaccine immunogenicity.