Background and Objectives The effects of the SARS-CoV-2 vaccination and infection on clinical outcomes, including relapse risk, have been insufficiently explored in people with multiple sclerosis (PwMS). The objectives of this study were to determine the incidence of new neurologic symptoms or symptom recrudescence among PwMS who received the SARS-CoV-2 vaccine, characterize outcomes after SARS-CoV-2 infection, and assess MS-specific determinants of vaccine hesitancy. Methods Online surveys that assessed incidence and severity of SARS-CoV-2 infection, vaccination status/type, reasons for vaccine deferral, and postvaccination symptoms were administered to PwMS. Medical charts were reviewed for consenting respondents. Associations between infection, postvaccination outcomes, and clinical characteristics were compared using chi(2) tests, 2-sample t tests, and adjusted logistic regression models. Results In total, 292 of 333 respondents were vaccinated, of whom 58 reported postvaccination side effects, most commonly among mRNA vaccine recipients (p = 0.02), younger patients (p < 0.01), and people with relapsing-remitting MS (p = 0.03). Twelve percent endorsed recrudescence of existing MS symptoms, while 3 endorsed new neurologic symptoms postvaccination. Sixty-two participants reported SARS-CoV-2 infection since the start of the pandemic, more frequent in younger individuals (1-year odds ratio OR = 0.958, 10-year OR = 0.649, p < 0.01). Neither disease-modifying therapy nor B-cell therapies specifically were associated with vaccine side effects, neurologic symptoms, or SARS-CoV-2 infection. Twenty-one percent of unvaccinated cited a desire for provider guidance before vaccination. Discussion Our findings provide new data to suggest that among PwMS who received SARS-CoV-2 vaccination, clinical disease worsening is rare and mostly associated with symptom recrudescence, as opposed to new relapses. Postvaccination side effects may occur more often among mRNA vaccine recipients and in younger individuals.
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