Background: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. Methods: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. Results: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p
