Self-reported longitudinal COVID-19 vaccination reactogenicity profiles in persons with multiple sclerosis

Background: Preventing severe COVID-19 associated outcomes continues to be a priority for persons with multiple sclerosis (PwMS). We previously reported in an interim analysis that short-term reactions to the first and second SARS-CoV-2 vaccines experienced by PwMS were mostly self-limiting and similar to reactions experienced by the general population. Objectives: First, to report short-term reactogenicity experienced by PwMS in relation to the first through fourth SARS-CoV-2 vaccines. Second, to report on short-term reactogenicity in PwMS for different sequences of the first three vaccines. Methods: Between March 2021 to March 2023, PwMS electronically self-reported SARS-CoV-2 vaccines, local and systemic reactions within 24 hours for each vaccine, and other clinical and demographic information. Multivariable models examined associations with reactogenicity after the first, second, third, and fourth vaccine. Similar models examined associations with reactogenicity after the third vaccine for specific vaccine sequences. Results: There were 1,087 PwMS, 722 PwMS, 263 PwMS, and 110 PwMS who provided information on the first and second vaccine and subsequent vaccines/boosters, respectively. 60 % reported a reaction after the first vaccine, compared to 71 % after the second, 62 % after the third, and 54 % after the fourth. 17 % reported a severe reaction after the first vaccine, while 22 % after the second, 16 % after the third, and 14 % after the fourth. Across most models, age and being on an sphingosine-1-phosphate receptor modulator were inversely associated with experiencing a reaction. Those who received mRNA-1273 (M) vs BNT162b2 (B) vaccine as the first through third vaccine, appeared to experience a high burden of reactions. Disease course, disease severity, and other demographic attributes were not associated with reactions after the third and fourth vaccines. PwMS who had the M-M-M sequence were more likely to report any and severe local reactions, the B-B-M sequence were more likely to report any severe and any severe systemic reactions, while the M-M-B sequence were less likely to report any reaction, in comparison to PwMS who only had the B-B-B sequence. Discussion: Our findings demonstrate that, in general, the short-term vaccine reactions experienced by PwMS are self-limiting, and their frequencies decrease with each subsequent vaccine/booster after peaking in response to