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Outcomes and Risk Factors Associated With SARS-CoV-2 Infection in a North American Registry of Patients With Multiple Sclerosis

Educational Objective
To identify the key insights or developments described in this article
0.5 Credit CME
Key Points

Question  How do patients with multiple sclerosis (MS) who have COVID-19 fare and are there patient and disease characteristics associated with worse outcome?

Findings  In this registry-based cross-sectional study of 1626 North American patients with MS and COVID-19 infection, ambulatory disability, both nonambulatory and requiring assistance to walk, was independently associated with increased odds of poor clinical severity levels after adjusting for other risk factors. Other factors including older age, male sex, Black race, cardiovascular comorbidities, and corticosteroid use in the past 2 months were associated with increased odds of increasing clinical severity compared with those not requiring hospitalization or worse.

Meaning  Identification of risk factors can improve the treatment of patients with MS and COVID-19 by alerting clinicians of patients requiring more intense treatment or monitoring.


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.

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Article Information

Corresponding Author: Amber Salter, PhD, Division of Biostatistics, Washington University in St Louis, 660 Euclid Ave, Campus Box 8067, St Louis, MO 63110-1093 (amber@wustl.edu).

Accepted for Publication: February 19, 2021.

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

Correction: This article was corrected on May 3, 2021, to fix an error in the Discussion.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Salter A et al. JAMA Neurology.

Author Contributions: Dr Salter had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Salter, Fox, Newsome, Li, Costello, Bebo, Rammohan, Cutter, Cross.

Acquisition, analysis, or interpretation of data: Salter, Fox, Newsome, Halper, Li, Kanellis, Bebo, Rammohan, Cutter, Cross.

Drafting of the manuscript: Salter, Halper, Cross.

Critical revision of the manuscript for important intellectual content: Fox, Newsome, Li, Kanellis, Costello, Bebo, Rammohan, Cutter, Cross.

Statistical analysis: Salter, Cutter.

Obtained funding: Bebo, Cutter.

Administrative, technical, or material support: Salter, Li, Kanellis, Bebo, Rammohan, Cutter, Cross.

Supervision: Newsome, Bebo.

Conflict of Interest Disclosures: Dr Salter reports grants from National Multiple Sclerosis Society and is a statistical editor for Circulation: Cardiovascular Imaging during the conduct of the study. Dr Fox reports personal fees from AB Science, Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic Therapeutics, Novartis, Sanofi, Teva Pharmaceutical, and TG Therapeutics and clinical trial contract and research grant funding from Biogen and Novartis during the conduct of the study. Dr Newsome reports personal fees from Biogen, Novartis, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, BioIncept, Autobahn, Celgene, and MedDay and other support from Biogen, Novartis, Genentech, National Multiple Sclerosis Society, US Department of Defense, and Patient-Centered Outcomes Research Institute paid to their institution outside the submitted work. Dr Li reports personal fees from Biogen and personal fees from Sanofi Genzyme; grants from Sanofi Genzyme, Roche, Novartis, and MS Society of Canada; is emeritus director of the University of British Columbia Multiple Sclerosis/Magnetic Resonance Imaging Research Group, which has been contracted to perform central analysis of magnetic resonance imaging scans for therapeutic trials with Roche and SanofiGenzyme and has received grant support for investigator-initiated studies from Sanofi Genzyme, Novartis, and Roche; and has served on the Progressive Multifocal Leukoencephalopathy–Multiple Sclerosis Steering Committee for Biogen and given lectures, supported by nonrestricted education grants from Academy of Healthcare Learning, Biogen, Consortium of Multiple Sclerosis Centers, and Sanofi Genzyme outside the submitted work. Dr Rammohan reports grants from Biogen, Novartis, Genzyme, Roche Genentech, Alexion, EMD Serono, MedDay Pharma, TG Therapeutics, and US Department of Defense and personal fees from Biogen, Novartis, Genzyme, Roche Genentech, Alexion, and EMD Serono outside the submitted work. Dr Cutter reports personal fees for serving on the data and safety monitoring boards of AstraZeneca, AveXis Pharmaceuticals, BioLineRx, Brainstorm Cell Therapeutics, Bristol Myers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Therapeutics, Hisun Pharmaceuticals, Mapi Pharma, Merck, Merck/Pfizer, Opko Biologics, OncoImmune, Neurim Pharmaceuticals, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, Viela Bio, Vivus, National Heart, Lung, and Blood Institute (protocol review committee), Eunice Kennedy Shriver National Institute of Child Health and Human Development (obstetric pharmacology research units oversight committee); personal fees from consulting or serving on advisory boards of BioDelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein Buendel, Medimmune/Viela Bio, MedDay, Merck/Serono, Neurogenesis, Novartis, Osmotica Pharmaceuticals, Perception Neuroscience, Recursion/CereXis Pharmaceuticals, Regeneron, Reckover Pharmaceuticals, Roche, and TG Therapeutics; and is President of Pythagoras Inc, a private consulting company. Dr Cross reports personal fees from Biogen, Celgene (Bristol Myers Squibb), EMD Serono, Genentech, Greenwich Biosciences, Janssen, Novartis, and TG Therapeutics outside the submitted work; grants from EMD Serono and Genentech outside the submitted work; and is secretary of the Consortium of Multiple Sclerosis Centers Board of Governors (an elected position), which is a supporter of the COVID-19 Infections in MS Registry, along with National Multiple Sclerosis Society (US) and MS Society of Canada. No other disclosures were reported.

Funding/Support: Support for the COVID-19 Infections in MS Registry is provided by the National Multiple Sclerosis Society, the Consortium of Multiple Sclerosis Centers, and the MS Society of Canada. REDCap at Washington University in St Louis is supported by Clinical and Translational Science Award (CTSA) (grant UL1 TR000448) and Siteman Comprehensive Cancer Center and National Cancer Institute Cancer Center Support Grant (grant P30 CA091842).

Role of the Funder/Sponsor: The National Multiple Sclerosis Society had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: The COVID-19 Infections in MS Registry had robust participation from health care professionals across North America and we would like to thank all those who contributed information to this effort.

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