Risk Factors for COVID-19 Disease Severity in Patients with Multiple Sclerosis in North America

March 2022

Previous small studies have suggested that disability and age are associated with the severity of SARS-CoV-2 infections in patients with multiple sclerosis (MS). More detailed analysis from a larger and more diverse population would aid healthcare providers in identifying which patients require more careful monitoring.

To address this gap in knowledge, Salter and colleagues carried out a cross-sectional study using data obtained from the COVID-19 Infections in MS (COViMS) Registry, a registry with deidentified data from cases of SARS-CoV-2 infection in people with MS in North America. Their analysis covered patient reports from April 1, 2020, to December 12, 2020. There were 1626 patients with MS and SARS-CoV2 infections from the United States, Canada, and Mexico in the COViMS Registry during this period. More than 80% of patients had relapsing-remitting MS, 9.5% were nonambulatory, and half had ≥1 comorbidities. A total of 54 patients died of COVID-19, for a mortality rate of 3.3%.

The investigators determined the fraction of patients with each of 4 levels of COVID-19 severity (not hospitalized, hospitalization only, intensive care unit [ICU] and/or required ventilator support, and death) and correlated the severity levels with patient characteristics.

The demographic characteristics strongly associated with more severe COVID-19 outcomes in people with MS were male sex, age, and black race. Black race was associated with increased odds of hospitalization and ICU admission and/or ventilator support compared with white race; however, black race was not associated with increased odds of death from COVID-19. “Altogether, the worse outcomes observed for Black patients with MS indicate that close clinical monitoring of COVID-19 in these patients is warranted,” the investigators advised.

Among the clinical characteristics most associated with disease severity were hypertension, diabetes, morbid obesity, and having multiple comorbidities, similar to what is seen for people without MS.

They also analyzed the association of outcome severity with MS disability. Requiring assistance to walk and being nonambulatory were each associated with an increased risk of more severe outcomes. Being nonambulatory was associated with a 25.4-fold risk of death from COVID-19, the strongest association seen in the study.

The investigators looked for an association between disease severity and 17 different disease-modifying therapies that patients were taking at the time of COVID-19 diagnosis. Patients taking anti-CD20 monoclonal antibody therapies had higher risks for hospitalization compared with patients not taking any disease-modifying therapy. The risk was 4.5-fold greater for rituximab and 1.63-fold greater for ocrelizumab. The investigators noted that the association of anti-CD20 therapies with disease severity was also found in several previously published studies of MS patients with COVID-19 in other regions of the world.

In addition, taking glucocorticoids in the previous 2 months was associated with a 2.6-fold increased risk for hospitalization, likely due to the effects of glucocorticoids on the immune system. The association of recent glucocorticoid use with ICU admission and/or ventilator support or death was not significant.

“Knowledge of these risk factors may enable clinicians caring for patients with MS to improve monitoring and treatment of COVID-19,” the investigators stated.

The investigators said that one limitation of the study was that the COViMS Registry contains only data that are voluntarily submitted by healthcare providers. This may have biased the registry against less severe cases. Another limitation was that many of the cases were from the Northeastern United States because of the severity of the pandemic in that region during the time of the study. The COViMS Registry is ongoing, and the analysis could be repeated in the future, by which time it will likely be more representative of populations and geographic regions of North America.


Salter A, Fox RJ, Newsome SD, et al. Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis. JAMA Neurol. 2021;78:699-708.

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