Changes in vaccination status, willingness and knowledge in patients with multiple sclerosis: Results from a five-year longitudinal study

Background Multiple sclerosis (MS) is a chronic immune-mediated disease requiring long-term management. Both the disease itself and disease-modifying therapies increase susceptibility to severe infections. Ensuring adequate vaccination in patients with MS is therefore essential. However, vaccine hesitancy and suboptimal vaccination coverage remain major clinical challenges. Objectives To comprehensively evaluate changes in vaccination status, vaccination willingness and vaccination-related knowledge in patients with MS over a five-year interval spanning the pre-/early and post-pandemic periods of coronavirus disease 2019, and to identify factors associated with vaccination status and vaccine uptake. Design Longitudinal observational cohort study at a single German MS center. Methods Patients with MS ( n =175) were assessed at baseline (August 2019 – June 2020) and follow-up (October 2024 – August 2025) using structured questionnaires and a review of vaccination records. The documented vaccination status for 26 vaccines was compared with patients’ self-reported vaccination status. Longitudinal changes and determinants of vaccination status were analyzed using paired statistical tests and logistic regression models. Results The patient cohort was predominantly female (70.3%) and had a mean age of 45.8 years and a median disease duration of 7 years at baseline. General vaccination willingness declined from 81.1% at baseline to 66.3% at follow-up ( p =0.001). This occurred despite a marked increase in reported vaccination counseling within the past year (34.3% to 70.8%, p <0.001) and in vaccination monitoring by neurologists (5.7% to 47.7%, p <0.001). At follow-up, vaccination coverage was highest for tetanus (87.9%), diphtheria (84.7%) and poliomyelitis (84.3%). A pronounced self-awareness gap was observed: typically fewer than 50% of patients who believed they were protected had a complete vaccination status, e.g., for pneumococcal, herpes zoster, influenza and varicella. Vaccination-related concerns, including fear of side effects and MS worsening, were negatively associated with complete vaccination status or vaccine uptake, whereas prior influenza vaccination was positively associated. Conclusion Despite intensified vaccination counseling, vaccination willingness declined markedly, suggesting post-pandemic vaccination fatigue in patients with MS. Persistent discrepancies between perceived and documented vaccination status and the impact of vaccine-related concerns highlight the need for more targeted strategies to strengthen vaccination confidence and improve immunization coverage.