Remote Observational Research for Multiple Sclerosis: A Natural Experiment.

BACKGROUND AND OBJECTIVES: Prospective, deeply phenotyped research cohorts monitoring individuals with chronic neurologic conditions, such as multiple sclerosis (MS), depend on continued participant engagement. The COVID-19 pandemic restricted in-clinic research activities, threatening this longitudinal engagement, but also forced adoption of televideo-enabled care. This offered a natural experiment in which to analyze key dimensions of remote research: (1) comparison of remote vs in-clinic visit costs from multiple perspectives and (2) comparison of the remote with in-clinic measures in cross-sectional and longitudinal disability evaluations. METHODS: Between March 2020 and December 2021, 207 MS cohort participants underwent hybrid in-clinic and virtual research visits; 96 contributed 100 "matched visits," that is, in-clinic (Neurostatus-Expanded Disability Status Scale [NS-EDSS]) and remote (televideo-enabled EDSS [tele-EDSS]; electronic patient-reported EDSS [ePR-EDSS]) evaluations. Clinical, demographic, and socioeconomic characteristics of participants were collected. RESULTS: The costs of remote visits were lower than in-clinic visits for research investigators (facilities, personnel, parking, participant compensation) but also for participants (travel, caregiver time) and carbon footprint (p < 0.05 for each). Median cohort EDSS was similar between the 3 modalities (NS-EDSS: 2, tele-EDSS: 1.5, ePR-EDSS: 2, range 0.6.5); the remote evaluations were each noninferior to the NS-EDSS within ±0.5 EDSS point (TOST for noninferiority, p < 0.01 for each). Furthermore, year to year, the % of participants with worsening/stable/improved EDSS scores was similar, whether each annual evaluation used NS-EDSS or whether it switched from NS-EDSS to tele-EDSS. DISCUSSION: Altogether, the current findings suggest that remote evaluations can reduce the costs of research participation for patients, while providing a reasonable evaluation of disability trajectory longitudinally. This could inform the design of remote research that is more inclusive of diverse participants.

SARS-CoV-2 Infection and Vaccination Outcomes in Multiple Sclerosis.

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 χ2 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.