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Risk of Multiple Sclerosis Among Persons with Epstein Barr Virus-Positive Mononucleosis: A Population-Based Study

Jennifer L St Sauver1, Susan Audrey Hall2, Robert M Jacobson3

  • 1Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

Neurology Open Access
|April 23, 2026
PubMed
Abstract

Insights

Epstein Barr Virus (EBV)-positive infectious mononucleosis (IM) significantly increases the risk of developing multiple sclerosis (MS). This study confirms a strong association between laboratory-confirmed EBV-positive IM and a higher likelihood of MS diagnosis.

Area of Science:

  • Neurology
  • Virology
  • Epidemiology

Background:

  • Previous studies on Epstein Barr Virus (EBV)-positive infectious mononucleosis (IM) and multiple sclerosis (MS) risk often lacked laboratory confirmation or relied on less precise diagnostic methods.
  • This research addresses limitations by focusing on laboratory-confirmed EBV-positive IM and verified MS cases.

Purpose of the Study:

  • To determine if laboratory-confirmed EBV-positive IM is associated with an increased risk of developing multiple sclerosis (MS).
  • To provide robust evidence for the link between EBV infection during mononucleosis and subsequent MS development.

Main Methods:

  • A population-based retrospective cohort study was conducted using medical records from the Rochester Epidemiology Project.
  • Individuals with laboratory-confirmed EBV-positive IM were identified and matched with a control group without IM.
  • Multivariate Cox proportional hazard models were employed to analyze the association between EBV-positive IM and MS risk, with MS cases verified by expert chart review.

Main Results:

  • The study included 4,721 individuals with EBV-positive IM and 14,163 controls.
  • During follow-up, 0.17% of the EBV-positive IM group developed MS, compared to 0.07% in the control group.
  • EBV-positive IM was associated with a 3.14-fold increased risk of developing MS (aHR: 3.14, 95% CI: 1.18-8.34).

Conclusions:

  • Laboratory-confirmed EBV-positive infectious mononucleosis is linked to a substantially higher risk of multiple sclerosis.
  • These findings reinforce the importance of investigating preventive strategies targeting EBV to mitigate the long-term impact of MS.
Keywords:
[ 142 ] Viral infections[ 41 ] Multiple sclerosis[ 54 ] Cohort studies[ 59 ] Risk factors in epidemiology

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