Immunogenicity, efficacy and safety of mRNA-COVID-19 vaccines in people with multiple sclerosis

ABSTRACT

Introduction: Knowledge regarding the development of protective immunity after COVID-19 vaccines is needed to guide medical, political and public health measures against the current and future pandemics. Objectives and Aims: To characterise and compare the safety, immunogenicity and efficacy of mRNA-COVID-19 vaccines in people with multiple sclerosis (pwMS) and healthy controls (HCs). Method(s) All pwMS vaccinated against COVID-19 in Norway were invited to participate in an ongoing observational cohort study (NevroVAX) from March 2021. Demographic-, immunisation-and disease-specific data were acquired from patient journals, web-questionnaires, the Norwegian Immunization Registry and Surveillance System for Communicable Diseases. Antibodies to full length spike protein and the receptor-binding domain (RBD) from SARS-CoV-2 were measured using a bead-based flow cytometric assay, while cellular immunity was investigated using high dimensional multiparameter analyses. Results and Conclusion(s) To date, 5545 pwMS were included with results available regarding humoral responses in 3021 (mean follow-up time 257 days), cellular responses in 140, and clinical efficacy in 900 pwMS. Those treated with anti-CD20 therapy or sphingosine-1-phosphate receptor modulators (S1PM) had weak humoral immune responses after two doses of mRNA-COVID-19 vaccines (80% and 91% <200 BAU/ml, respectively). Additional vaccine doses were safe and associated with a modest increase of anti-SARS-CoV-2 spike RBD IgG antibodies (72% and 83% <200 BAU/ml after three, 74% and 89% <200 BAU/ml after four doses). Humoral responses were weaker after all vaccine doses in pwMS (also in those without treatment) compared to HCs. Cellular responses were significantly attenuated in pwMS treated with S1PM. An elevated rate of non-omicron breakthrough infections was observed in the anti-CD20 (19%), S1PM (18%), and HSCT (14%) group, compared to pwMS on other high-or low-efficacy DMTs or without treatment (13%, 10%, and 7%, respectively). Among 900 pwMS treated at the same hospital, 12 (1%) were hospitalized due to COVID-19, one requiring intensive care. Our results show that antibody responses correlated with the rate of breakthrough infections but is not necessarily indicative of a failed cellular or clinical response to vaccination, and that pwMS have weaker humoral responses than HCs regardless of treatment status. Updated, real-world data from NevroVAX will be presented at ECTRIMS 2022.