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.

Rocco Capuano, Luca Prosperini, Manuela Altieri, Lorena Lorefice, Roberta Fantozzi, Paola Cavalla, Clara Guaschino, Marta Radaelli, Cinzia Cordioli, Viviana Nociti, Laura Boffa, Paolo Ragonese, Maria Di Gregorio, Federica Pinardi, Valentina Torri Clerici, Giovanna De Luca, Alberto Gajofatto, Damiano Paolicelli, Carla Tortorella, Claudio Gasperini, Claudio Solaro, Eleonora Cocco, Alvino Bisecco, Antonio Gallo, Giovanni Di Dio