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Risk Factors Identified That Predispose Patients With MS, COVID-19 to Worse Outcomes


Among these factors, having a higher degree of disability from multiple sclerosis (MS) was independently associated with higher morbidity and mortality risks from having a comorbid case of COVID-19.

For patients with multiple sclerosis (MS), having a higher degree of disability and a concomitant case of COVID-19 meant a greater likelihood of adverse mortality and morbidity outcomes, according to study findings published today in JAMA Neurology.

When explaining why they took up this study, the authors noted, “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.” They added that because MS and its disease-modifying therapies affect the immune system, concern is elevated for these patients on how COVID-19 affects them and in turn how their MS medications could shape their outcomes from COVID-19.

For example, they found increased risks of hospitalization among patients taking rituximab (4.5 times) or ocrelizumab (1.63 times). Glucocorticoid use, too, was associated with higher risks of both hospitalization (2.0 times) and death (4.0 times) if it occurred in the 2 months prior to a COVID-19 diagnosis.

Their registry-based cross-sectional study encompassed deidentified data on 1626 patients with MS (mean [SD] age, 47.7 [13.2] years), of whom 82.7% had a lab-confirmed case of SARS-CoV-2 (the virus that cause COVID-19) infection; nearly half of the patients (49.5%) had 1 or more comorbidities (most common: hypertension, 22.0%; morbid obesity, 11.0%; diabetes, 9.1%).

Data from 47 states, Puerto Rico, 4 Canadian provinces, and Mexico were provided by the COVID-19 Infections in MS Registry for North America for April 1 to December 12, 2020. Eighty percent of the patients had relapsing-remitting MS, 74.0% were female, and 61.5% were non-Hispanic White.

Clinical outcomes were evaluated as they pertained to 4 disease severity levels: not hospitalized, hospitalization only, admission to the intensive care unit (ICU) and/or required ventilator support, and death.

A 3.3% (95% CI, 2.5%-4.3%) overall mortality rate was seen among the patients with comorbid MS and COVID-19, and of these patients, 79.6% were hospitalized, 53.7% required ICU admittance, and 46.3% needed ventilator support. Male sex and being Black were alone associated with 41% and 47% greater odds, respectively, of hospitalization alone, while “older age, obesity, and several cardiovascular comorbidities were associated with more severe COVID-19,” the authors noted.

Greater odds of adverse outcomes per ambulatory disability and older age (every 10 years) echoed across all disease severity levels above not hospitalized:

  • Ambulatory disability:
    • There was a 2.8 (95% CI, 1.6-4.8) times greater risk of hospitalization only
    • There was a 3.5 (95% CI, 1.6-7.8) times greater chance of admittance to the ICU/needing ventilator support
    • The risk of death was 25.4 (95% CI, 9.3-69.1) times greater
  • Age:
    • There was a 1.3 (95% CI, 1.1-1.6) times greater risk of hospitalization only
    • There was a 1.3 (95% CI, 0.99-1.7) times greater chance of admittance to the ICU/needing ventilator support
    • The risk of death was 1.8 (95% CI, 1.2-2.6) times greater

When broken down by age grouping, the mortality risk with older age becomes even more apparent: 35 to 44 years, 1.2% (95% CI, 0.4%-25.9%); 45 to 54 years, 2.1% (95% CI, 1.0%-4.0%); 55 to 64 years, 4.9% (95% CI, 2.8%- 7.8%); 65 to 74 years, 11.7% (95% CI, 7.0%-18.1%); and 75 years or older, 22.6% (95% CI, 9.6%-41.1%).

“For every 10-year increase in age, a 30% increased risk of both hospitalization alone and ICU admission and/or ventilation was identified,” the authors said. “Notably, there was a 76.5% increased risk of death for every 10-year age increase.”

Analyses also revealed elevated rates of COVID-19 symptoms in the study patients reporting fever as their chief symptom (n = 878; 55%):

  • Dry cough: 39.2%
  • Fatigue: 40.4%
  • Anosmia: 26%
  • Ageusia: 25.3%
  • Pain: 25.6%
  • Headache: 25.7%

Neurological symptoms were reported for 8.9% of the patients also reporting fever and mostly encompassed motor dysfunction (44.4%) and cognitive dysfunction (25.7%). Overall, symptoms usually lasted 7 to 13 (27.7%) or 14 to 20 days (27.6%) among patients reporting COVID-19 symptoms.

The authors note that some of their findings conflict with prior studies, so these patients should be closely monitored and their results confirmed with future studies.

“No clear association of MS diagnosis with risk of developing COVID-19 could be established in this study because of the unknown numbers at risk in the MS populations from whom cases were reported,” the authors concluded. “However, with more than 1600 reported patients with MS, the COViMS Registry provides evidence that ambulation disability, older age, and Black race are associated with worse COVID-19 clinical course in a North American MS population. Knowledge of these risk factors may enable clinicianscaring for patients with MS to improve monitoring and treatment of COVID-19.


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. Published online March 19, 2021. doi:10.1001/jamaneurol.2021.0688

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