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Multicenter Study
. 2025 Dec;12(12):2446-2459.
doi: 10.1002/acn3.70184. Epub 2025 Sep 5.

Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study

Chen Hu  1 , Jiyeon Son  2 , Lindsay McAlpine  3 , Elizabeth L S Walker  4 , Megan Dahl  4 , Emily Song  4 , Sugeidy Ferreira Brito  2 , Katelyn Kavak  5 , Kaho Onomichi  2 , Amit Bar-Or  6 , Christopher Perrone  6 , Claire S Riley  2 , Bianca Weinstock-Guttman  5 , Philip L De Jager  2 , Erin E Longbrake  3 , Zongqi Xia  4
Affiliations
Multicenter Study

Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study

Chen Hu et al. Ann Clin Transl Neurol. 2025 Dec.

Abstract

Background: Managing long COVID in people with multiple sclerosis and related disorders (pwMSRD) is complex due to overlapping symptoms. To address evidence gaps, we evaluated long COVID susceptibility in pwMSRD versus controls and its associations with multi-domain function and disability.

Methods: In this multicenter cross-sectional study, participants completed a survey covering 71 post-infection symptoms, distinguishing new-onset from worsening symptoms. We defined long COVID using the 2024 NASEM criteria. Logistic regression assessed long COVID odds. Linear and Poisson regression evaluated associations with function and disability.

Results: 969 pwMSRD (82.5% female, mean age 51.8 years, 63.5% infected) and 1003 controls (79.4% female, mean age 45.2 years, 61.2% infected) were included. PwMSRD had higher odds of long COVID (aOR = 1.6 [1.2-2.1]), with a stronger association when restricting to worsening symptoms (aOR = 2.3 [1.7-3.1]). Having long COVID was associated with worse physical function, cognition, and depression in both groups. PwMSRD with long COVID experienced greater physical function declines and more depression severity exacerbation than controls, and had faster disability progression compared to those without long COVID.

Conclusion: PwMSRD show increased susceptibility to long COVID, primarily driven by worsening symptoms. Long COVID contributes to more functional decline and disability worsening. Recognizing and managing long COVID is essential for pwMSRD.

Keywords: disability; long COVID; multiple sclerosis and related disorders; neurology; patient‐reported outcomes.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Study design. MSRD, multiple sclerosis and related disorders; MSReCOV, Multiple Sclerosis Resilience to COVID‐19; PDDS, Patient Determined Disease Steps; PROMIS, Patient‐Reported Outcomes Measurement Information System.
FIGURE 2
FIGURE 2
Participant disposition. MSRD, multiple sclerosis and related disorders; MSReCOV, Multiple Sclerosis Resilience to COVID‐19; PROMIS, Patient‐Reported Outcomes Measurement Information System; pwMSRD, people with multiple sclerosis and related disorders.
FIGURE 3
FIGURE 3
Prevalence of NASEM‐defined long COVID.
FIGURE 4
FIGURE 4
Associations between factors and NASEM‐defined long COVID. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) from multivariable logistic regression models evaluating factors associated with (A) overall NASEM‐defined long COVID, (B) long COVID based on new symptoms, and (C) long COVID based on worsening symptoms.
FIGURE 5
FIGURE 5
Multivariable linear regression for PROMIS physical function (left), cognitive function (middle), and depression (right). Model 1, NASEM‐defined long COVID overall as the main exposure; Model 2, NASEM‐defined long COVID on new symptoms as the main exposure; Model 3, NASEM‐defined long COVID on worsening symptoms as the main exposure.
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Update of

References

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