Real-world COVID-19 immunity in multiple sclerosis (CoVaR-MS): A longitudinal follow up study.

COVID-19 vaccination in Multiple Sclerosis (MS) has continued clinical relevance. Complex dosing and variability in immunosuppression/ immunomodulation from disease modifying treatments (DMTs) necessitate real-world studies of COVID-19 immunity. We aimed to evaluate if PwMS develop adequate and persistent serological and cellular COVID-19 immunity after vaccination. We conducted a real-world longitudinal study (n = 235) including PwMS (n = 205; Alemtuzumab, Dimethyl fumarate, Fingolimod, Interferon, Natalizumab, Ocrelizumab, no-DMT) and Healthy volunteers (HV) (n = 30). Serological and cellular immunity was tested at ≤18 and ≤24-month after completed COVID-19 vaccine-course. 97 % of both HV and PwMS were immune at ≤18-month, and 96.9 % PwMS and 100 % HV at ≤24-month, (OR 0.33, 95 % CI (0.09, 0.93), p = 0.05)). Both groups showed similar cellular immunity at both timepoints. Vaccine Adverse effects incidence was similar too. PwMS on Ocrelizumab were significantly less likely to have low serological immunity (p < 0.001 at both timepoints). They were more likely to have intact T cell responses than HV (OR 5.4, 95 % CI 1.28-22.60). Despite this, they had higher infections per person year. PwMS on Fingolimod also had low serological immunity (Odd's ratio 0.33; CI 0.11-0.97) which stayed low despite boosters and only 6 % showed intact cellular immunity, probably due to lymphopenia. Other DMT-treated PwMS (Natalizumab, Dimethyl Fumarate, Interferon, and no no-DMT) showed comparable COVID-19 serological and cellular immunity as HV. We report COVID-19 immunity clearly over time and across various DMT-groups. Ocrelizumab lowered serological but maintained cellular immunity; whilst Fingolimod lowered both. Data support boosters in PwMS, more so on Ocrelizumab and Fingolimod.