COVID-19 Not Linked to Long-term Worsening of RRMS: Iranian Study

COVID-19 does not seem to be linked to increased disability worsening or more relapses in the long term for people with relapsing-remitting multiple sclerosis (RRMS), an Iranian study suggests.

The study was relatively small, the researchers noted, indicating that more research is needed in the future to determine the impact of COVID-19 on MS disease activity.

The study, “Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study,” was published in BMC Neurology.

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Over the past couple of years, there have been concerns about whether COVID-19 could exacerbate the symptoms of multiple sclerosis. However, studies to date have only focused on changes in disease activity during or shortly after COVID-19.

Thus, a team of researchers in Iran set out to determine long-term changes in MS clinical outcomes in patients several months after recovering from COVID-19.

From a total of 1,500 patients assessed for eligibility, 53 were included in the analysis. These patients, most of whom were female and had a mean age of 38.4 years, were diagnosed with RRMS at least 54 weeks (about one year) before contracting COVID-19. They all agreed to an in-person follow-up visit at three months.

At study entry, clinical information — including coexisting diseases, disease duration, type of disease-modifying therapy, and COVID-19 diagnosis method, onset, and severity — were collected. For comparison purposes, the researchers also collected any clinical information recorded prior to COVID-19 infection.

In the group, four patients had diabetes, three had high blood pressure or other cardiovascular disease, and two had a deficiency in the thyroid hormone. Most (50 patients) were receiving some type of disease-modifying therapy.

Of the 53 patients, six were hospitalized due to COVID-19 “but managed to recover without complications,” the researchers wrote. Four of these patients were on dimethyl fumarate (sold as Tecfidera among others), one was on rituximab (which is used off-label in MS), and one was on interferon beta (sold as Avonex and Betaseron, among others).

Determining the effect of COVID-19 on disease activity can be difficult when there is a small number of patients who are followed for a relatively short period of time. To get around these limitations, the researchers used probable disability progression, defined as a rise in the Expanded Disability Status Scale score that was sustained for at least three months, as the study’s primary endpoint.

“This modification made the study more sensitive,” the researchers wrote. As a secondary endpoint, they looked at new or worsening symptoms lasting at least one day after a one-month remission period. These were referred to as acute relapses.

Results showed that being admitted to the hospital increased the likelihood of probable disability progression by 4.5 times compared with the period prior to having COVID-19. These patients also were about twice as likely to have an acute relapse.

While these findings suggest a possible link between COVID-19 severity and the worsening of RRMS activity, “this could not be confirmed due to lack of statistical significance,” the researchers wrote.

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Looking at the entirety of the patient sample, the proportion of patients with probable disability progression was actually lower after they had COVID-19 than before infection (18.9% vs. 5.7%). The proportion of patients experiencing relapses also was lower (30.2% vs. 20.8%).

This decrease “may be explained by a decoy effect of COVID-19, diverting the inflammatory cells to the lungs from the central nervous system,” the researchers wrote, adding that probable disability progression rates are “unlikely to be increased long after recovering from COVID-19.”

However, “the study lacked enough statistical power to rule out the possible increase in cumulative relapse rates, and the possible decrease in [disability progression]-free and relapse-free survivals after recovering from COVID-19,” they added.

The small sample size and the use of a possibly “over-sensitive” endpoint were noted as limitations of the study.

“The findings of this study are subject to replication in future settings and should be taken into consideration with caution,” the researchers wrote.