Does Epstein-Barr Virus-Positive Infectious Mono Impact MS Risk?

Patients with a history of Epstein-Barr virus (EBV)-positive infectious mononucleosis (IM) are more than 3 times as likely to develop multiple sclerosis (MS), according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, held in West Palm Beach, Florida from February 27 to March 1.

Most EBV infections occur early in life and do not require clinical intervention, making EBV seropositivity common in the general population. However, mounting evidence suggests that the subset of patients who develop EBV-positive IM seem to be at increased risk of developing demyelinating diseases, including MS.

To evaluate the long-term risk for MS after EBV-positive IM, researchers sourced data for this population-based study from the Rochester Epidemiology Project (REP). Patients (n=4721) who were diagnosed with EBV-positive IM between 1998 and 2011 were matched in a 3:1 ratio with non-EBV control individuals (n=14,163) and the 2 cohorts were assessed for incident diagnosis of MS or other demyelinating diseases.

In the chart review, a total of 18 MS and 5 other demyelinating diseases were observed.

During a median follow-up of 6 to 8 years, MS occurred at a rate of 2.25 (95% CI, 0.97-4.44) per 10,000 person-years among EBV-positive IM cases compared with 0.77 (95% CI, 0.47-1.60) per 10,000 person-years among control individuals.

Having a history of EBV-positive IM associated with increased risk for MS (adjusted hazard ratio [aHR], 3.03; 95% CI, 1.15-8.01) and MS or other demyelinating diseases (aHR, 3.77; 95% CI, 1.61-8.86), in which the association was primarily driven by MS risk.

The limitations of this study included the small number of MS and demyelinating disease cases and the short follow-up duration.

“Individuals diagnosed with EBV-positive IM are at more than threefold increased risk of developing MS and other demyelinating diseases. These findings provide strong evidence for the role of EBV in the pathogenesis of MS and suggest that EBV preventive strategies could reduce the burden of MS and related neurological conditions.”

Disclosure: This research was supported by Moderna Tx, Inc. Please see the original reference for a full list of disclosures