Registry Studies Reassure on Impact of COVID-19 in People With MS

COVID-19 does not impact symptom severity or disease trajectory in MS, and the likelihood of long COVID appears to be low in patients with MS following COVID-19 infection. So conclude two new studies of patient-reported information from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry.

“Our analyses enhance the general understanding of the consequences of COVID-19 infection in people with MS and should be reassuring to both people with MS and the clinicians who treat them,” says Cleveland Clinic neurologist Robert J. Fox, MD, a co-author of both studies. “The data indicate that exposure to COVID-19 is not likely to worsen MS and, although symptoms of post-acute sequelae of the virus do occur in MS patients, the incidence is low.”

Backdrop to the studies

MS is associated with an increased risk of infection and infection-related hospitalization, and systemic infections may exacerbate disability in individuals with the disease. How COVID-19 may affect MS outcomes is not well understood, however, and results are conflicting from the few studies that exist.

In people with MS, post-acute sequelae of COVID-19 (PASC), or long COVID, also is poorly understood. Common PASC symptoms are nonspecific and may overlap with those of MS, such as fatigue and foggy thinking. As a result, determining whether lingering symptoms represent post-COVID persistence or worsening of MS is challenging.

To elucidate these issues, Dr. Fox and colleagues examined cross-sectional, longitudinal data self-reported by people with MS participating in the NARCOMS Registry through surveys conducted by the registry every spring and fall. Their findings about the effects of COVID-19 infection on MS symptom severity and disability were published online in Neurology, and those about PASC in MS patients were published online in Multiple Sclerosis Journal.

Effect of COVID-19: findings in brief

A controlled interrupted time series (ITS) design was used for the study of COVID-19 symptom and disability severity. As the researchers explain in their study report, ITS is a quasi-experimental approach that “compares the change in the outcome of interest over time between 2 groups, before and after the intervention or exposure of interest.” For this study, each patient served as their own control, so the two groups were the patients before and then after their COVID-19 infection.

The NARCOMS Registry surveys included for this study were the seven conducted from spring 2020 through spring 2023. The study included 796 registry participants who reported a COVID-19 infection (confirmed by a home or lab test) and 1,336 participants who reported no infection during the period from spring 2020 through fall 2022. Having a comparison group that was uninfected allowed the researchers to account for potential effects of the pandemic, such as changes in physical activity and social interactions.

Trajectories of participants’ MS symptoms and disability and associations with COVID-19 were assessed with participant-reported scales. Symptom severity across 12 key domains common to MS was measured with SymptoMScreen (SMSS), and disability severity was quantified with patient-determined disease steps (PDSS).

In the both the infected and uninfected cohorts, after adjustment for participant characteristics, both symptom severity (SMSS) and disability (PDSS) increased nominally over time. Among infected patients, both immediately after infection and at median follow-up of 18 months, COVID-19 had no significant impact on MS symptom progression or disability compared with their pre-infection status.

“We found that compared with an uninfected control cohort, COVID-19 had no effect on symptom and disability trajectories in people with MS who had a COVID-19 infection,” Dr. Fox observes. He adds that the study’s ITS design feature is a particular strength, as it allowed for accounting of both measured and unmeasured confounders and isolated the specific impact of COVID-19 infection.

Effect of PASC: findings in brief

The second study examined the prevalence of PASC by drawing on NARCOMS Registry participants’ responses to the spring 2023 NARMCOMS survey, which focused on infections they had in the 6 months prior to the survey. Responses were used to compute each participant’s individual PASC score, a composite of symptoms that have been commonly reported following COVID-19 infection as identified through the National Institutes of Health-supported RECOVER study. Participants with a score ≥ 12 by the RECOVER scoring system were classified as having PASC, as recommended from the RECOVER study.

“Importantly,” Dr. Fox adds, “the NARCOMS survey examined not only COVID-19 infections but also non-COVID-19 infections and uninfected individuals to understand the specificity of PASC symptoms to COVID-19 and other infections.”

Of the 2,927 registry participants included in the analysis, 10% had a COVID-19 infection, 29.1% had a non-COVID-19 infection, 8.4% had both COVID-19 and at least one other infection, and 52.4% were uninfected during the 6 months prior to the survey.

The survey also asked participants about the symptoms they experienced in relation to infections. Prevalence of fever, cough, loss of smell/taste and dyspnea were twice as high in the participants who had experienced a recent infection compared with those who had not experienced a recent infection. Only 1.5% of the participants with COVID-19 had persistent new symptoms that met the criteria for PASC.

“Prevalence of new persistent symptoms following infection in people with MS was low across all groups,” Dr. Fox notes, “and the proportion of registry participants currently experiencing symptoms consistent with PASC was similar between those with and those without COVID-19. Together, these findings suggest that a general post-acute infectious effect may occur in patients with MS, albeit at low incidence. Additionally, the overlap of MS symptoms with PASC symptoms complicates the identification of PASC in individuals with MS.”

Insights and reassurance

The investigators note that both studies were limited by potential bias owing to the voluntary nature of respondents’ participation in the NARCOMS Registry. “Despite these limitations,” write the authors of an editorial accompanying the first study, “[this study] offers much-needed insights into the relationship between COVID-19 and MS progression…and offers reassurance regarding the effects of COVID-19 on the disease course in populations at increased risk of disease progression.”