COVID-19 Infection Does Not Impact Symptom Severity or Disability Trajectory in Multiple Sclerosis

Amber Salter, PhD

Using a controlled interrupted time series (ITS), a quasiexperimental study design, researchers found that COVID-19 infection was not associated with immediate changes in symptom severity or disability in patients with multiple sclerosis (MS), nor did it change the trajectories of these outcomes over a median follow-up of 18 months. Published in Neurology, the study overall enhanced the understanding of the consequences of infection in people with MS and are "reassuring" regarding the impact of COVID-19 on the course of MS, according to study authors.

The spring 2023 survey was sent to 7782 participants, with 5239 (67.3%) responding. Among these, 344 participants were excluded for not meeting criteria such as reporting clinician-diagnosed MS, being aged 18 or older, or being a US resident, and 108 more were excluded for not answering the COVID-19 question. Of the 4787 eligible participants, 2106 (44.0%) reported confirmed COVID-19 through a lab or at-home test. In the COVID-19 infection cohort, 796 participants met the criteria for analysis within a 30-day window around infection, with a median time from infection to index of 4 months. Using a 90-day window, 685 participants were eligible for analysis.

Led by Amber Salter, PhD, the Kenney Marie Dixon-Pickens Distinguished Professorship in Multiple Sclerosis Research at UT Southwestern Medical Center, the study compared symptoms of infected patients vs to those not infected using the SymptoMScreen (SMSS). In the uninfected cohort, 1,534 (32.0%) reported no COVID-19 or other infections in the 6 months before the survey, and 1,336 had at least 3 surveys completed before and after this period. Between the 2 groups, the COVID-19 infection cohort was younger, had more women, higher income and education, lower disability, earlier symptom onset, and more frequent anti-CD20 DMT use.

Results from the study showed that the change in the SMSS total score each month before or after the index period (P = .73; P = .98, respectively) did not differ between the infection and uninfected cohorts, even after adjusting for age at index, sex, race, education level, disease duration at index, and disease-modifying therapy. The SMSS score increased slightly by 0.02 points per month from before to after the index survey, with no significant difference between groups (p = 0.75). COVID-19's immediate impact on SMSS was minimal (less than 0.5 points) and similar across groups (p = 0.14). These findings were consistent when using a 90-day window, adjusting for covariates like disability and vaccination status, and in the weighted cohort.

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Change in disability, measured through Patient-Determined Disease Steps (PDDS), did not differ between the groups in the pre- and post-periods (P = .70; P = .72, respectively); however, investigators did observed a small increase in the rate of worsening over time between both groups (uninfected, β = −0.00003 [SE, 0.0004]; COVID-19, β = −0.0004 [SE, 0.0007].These small increases between the groups (P = .62), as well as the immediate change in disability after the index period (P = .37) was not different between the cohorts.

"Within an individual symptom domain, few changes were detected between groups or because of the immediate effect of COVID-19,” the study authors wrote. "Within the COVID-19 cohort, most symptom trajectories changed little from their pre–COVID-19 rates. Symptoms such as fatigue and cognitive function, which are common in both MS and COVID-19, were consistent over time and compared with uninfected controls."

"Similarly, while the emotional well-being of people with MS was adversely affected during the pandemic, we noted minor changes in specific symptom domains compared with prepandemic trajectories in both those with COVID-19 and the uninfected cohort. These changes may be due to the instrument used in our study to assess these symptoms, being less sensitive compared with a specific scale for each domain," Salter et al added.

This study's strengths include a controlled ITS design with longitudinal data to assess symptom changes and compare with a COVID-19 uninfected control group. However, limitations include potential selection bias from volunteer participants in the NARCOMS Registry, a sample skewed toward older individuals, and reliance on participant-reported measures, which may lack sensitivity to change. While large sample sizes reduced statistical error, clinically meaningful differences were minimal. Challenges included potential inaccuracies in COVID-19 test results, unaccounted COVID-19 severity, and unmeasured time-varying factors, though the control group addressed broader trends over time.

REFERENCE
1. Salter A, Lancia S, Cutter GR, Fox RJ, Marrie RA. Effects of COVID-19 infection on symptom severity and disability in multiple sclerosis. Neurology. 2025;104(2). doi:10.1212/WNL.0000000000210149