COVID-19 outcomes in patients with multiple sclerosis: Understanding changes from 2020 to 2022

<bold>Background: </bold>Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021.<bold>Objectives: </bold>We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022.<bold>Methods: </bold>This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity.<bold>Results: </bold>Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave (p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25-1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51-2.67]), obesity (OR = 2.36, 95% CI = [1.52-3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46-3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43-3.06] for EDSS 3-5.5 and OR = 4.53, 95% CI = [3.04-6.75] for EDSS >= 6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85-3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60-0.69]) or off (RR = 0.32, 95% CI = [0.30-0.33]) anti-CD20.<bold>Discussion: </bold>In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status.