Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections .

Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS. Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry . Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death . Data collection began April 1 , 2020, and is ongoing . Exposures: Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19 . Main Outcomes and Measures: Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death .

Results: Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7 %] ), were female (1202 [74.0 %] ), and had relapsing-remitting MS (1255 [80.4 %] ). A total of 996 patients (61.5 %) were non-Hispanic White , 337 (20.8 %) were Black, and 190 (11.7 %) were Hispanic/Latinx . The mean (SD) age was 47.7 (13.2) years, and 797 (49.5 %) had 1 or more comorbidity . The overall mortality rate was 3.3% (95% CI , 2.5% -4.3 %). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors (nonambulatory: hospitalization only, odds ratio [OR], 2.8 [95% CI , 1.6-4.8]; intensive care unit/required ventilator support, OR , 3.5 [95% CI , 1.6-7.8]; death, OR , 25.4 [95% CI , 9.3-69.1]; age [every 10 years]: hospitalization only, OR , 1.3 [95% CI , 1.1-1.6]; intensive care unit/required ventilator support, OR , 1.3 [95% CI , 0.99-1.7]; death, OR , 1.8 [95% CI , 1.2-2.6] ). Conclusions and Relevance: In this registry-based cross-sectional study, increased disability was independently associated with worse clinical severity including death from COVID-19 . Other risk factors for worse outcomes included older age, Black race, cardiovascular comorbidities, and recent treatment with corticosteroids . Knowledge of these risk factors may improve the treatment of patients with MS and COVID-19 by helping clinicians identify patients requiring more intense monitoring or COVID-19 treatment.