Summary: A new study has strengthened the link between infectious mononucleosis (mono) and Multiple Sclerosis (MS). By analyzing over two decades of health records, researchers found that individuals who contracted the Epstein-Barr virus (EBV) as teenagers or adults—resulting in a clinical case of mono—were three times more likely to develop MS later in life compared to those who did not.
While MS remains relatively rare, this study underscores the potential for future EBV vaccines to significantly reduce the global burden of the disease.
Key Facts
- Threefold Risk: After adjusting for smoking, race, and underlying health conditions (like diabetes and depression), the study found a 300% increase in MS risk for those with a history of mono.
- The Statistics: * Mono Group: 0.17% (8 out of 4,721) developed MS, representing 2.25 cases per 10,000 person-years.
- Control Group: 0.07% (10 out of 14,163) developed MS, representing 0.77 cases per 10,000 person-years.
- The Age Factor: EBV is nearly universal, but when contracted later in life (teens/adulthood) rather than in childhood, it often manifests as mono, which appears to be the specific risk-escalating event.
- Vaccine Implications: The study was supported by ModernaTX, Inc., which is currently developing vaccines to target EBV-associated conditions, including MS.
Source: AAN
Having the disease infectious mononucleosis, often called mono, caused by the Epstein-Barr virus is associated with an increased risk of developing multiple sclerosis (MS), according to a study published on April 1, 2026, in Neurology Open Access.
The Epstein-Barr virus is a herpes virus that is extremely common but causes no symptoms in most people. However, when a person contracts the virus as a teenager or adult, it can lead to mononucleosis. The Epstein-Barr virus is the most common cause of mono. The study does not prove that mono caused by the Epstein-Barr virus causes MS; it only shows an association.
“These results highlight the need for further research into ways to prevent infection with the Epstein-Barr virus,” said study author Jennifer L. St. Sauver, PhD, of the Mayo Clinic in Rochester, Minnesota.
“Preventing these infections could reduce the overall burden of MS. While MS is relatively rare, it carries the risks of significant disability and high treatment costs, and it usually develops when people are in their prime years of working and raising families.”
For the study, researchers examined more than two decades of health care records to find people who had a positive test for Epstein-Barr virus infection and a diagnosis of infectious mononucleosis. The 4,721 people the researchers identified were then each compared to three people of the same age and sex who had not had mono, or 14,163 people.
The people who had mono were followed for an average of six years. The people without mono were followed for an average of eight years. During that time, eight people with a history of mono developed MS, or 0.17%. This represented 2.25 cases per 10,000 person-years.
Person-years represent both the number of people in the study and the amount of time each person spent in the study. For the group without mono, 10 people developed MS, or 0.07%. This represented 0.77 cases per 10,000 person-years.
Researchers then adjusted for other factors that could affect the risk of MS, such as race and ethnicity, smoking status and whether participants had other conditions such as diabetes, depression and substance use disorders. After adjustment, they found that people with a history of mono were three times more likely to develop MS than people without mono.
“Mononucleosis is a relatively uncommon illness, but developing strategies to prevent infection with the virus that causes this disease could help us to lower the number of MS cases in the future,” St. Sauver said.
A limitation of the study is that participants were followed for an average of six to eight years, so it’s possible that MS could develop later in life for some people.
Funding: The study was supported by ModernaTX, Inc., which is developing vaccines to target multiple Epstein-Barr virus-associated conditions.
Key Questions Answered:
A: Definitely not. In this large study, only 0.17% of people with a history of mono developed MS. While the relative risk is three times higher, the absolute risk remains very low. Most people who have had mono will never experience neurological issues.
A: Scientists believe “molecular mimicry” might be at play. The Epstein-Barr virus hides in your B cells for life. In some people, the immune system might get confused and start attacking the brain’s myelin (insulation) because it looks similar to parts of the virus.
A: That is the ultimate goal. If we can prevent the initial EBV infection or the development of mono through vaccination, we might be able to “starve” MS of its primary environmental trigger. Companies like Moderna are already working on this.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this multiple sclerosis research news
Author: Natalie Conrad
Source: ANN
Contact: Natalie Conrad – ANN
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Risk of Multiple Sclerosis Among Persons With Epstein-Barr Virus–Positive Mononucleosis: A Population-Based Study” by Jennifer L. St. Sauver, Susan A. Hall, Robert M. Jacobson, B. Mark Keegan, Chun Fan, Roderick A. McPhee, Philip O. Buck, and John Diaz-Decaro. Neurology Open Access
DOI:10.1212/WN9.0000000000000082
Abstract
Risk of Multiple Sclerosis Among Persons With Epstein-Barr Virus–Positive Mononucleosis: A Population-Based Study
Background and Objectives
Previous studies examining associations between Epstein-Barr virus (EBV)–positive infectious mononucleosis (IM) and risk of multiple sclerosis (MS) frequently lacked laboratory confirmation of EBV-positive IM or relied on billing codes to identify MS. We assessed whether laboratory-confirmed EBV-positive IM was associated with an increased risk of developing verified cases of MS.
Methods
We conducted a population-based retrospective cohort study using medical records from the Rochester Epidemiology Project. We identified individuals with serologic evidence of EBV infection and an associated IM diagnosis (EBV-positive IM; exposed cohort) between 1998 and 2022. Age-matched (±1 year) and sex-matched individuals without evidence of IM (3:1 match) comprised the unexposed cohort. Incident MS cases were verified through blinded expert chart review. Multivariate Cox proportional hazard models were used to assess associations between EBV-positive IM and risk of MS.
Results
A total of 4,721 persons had EBV-positive IM (exposed cohort: 55% female, 70% < 20 years). The referent cohort included 14,163 persons without EBV-positive IM (55% female, 70% < 20 years). During follow-up (median, 6 years for exposed; 8 years for referents), MS developed in 8 individuals with EBV-positive IM (0.17%) and 10 referents (0.07%). EBV-positive IM was associated with a >3-fold increased risk of MS (adjusted hazard ratio: 3.14, 95% confidence interval: 1.18–8.34).
Discussion
EBV-positive IM was associated with a substantially higher risk of MS. Findings are consistent with previous studies and underscore the importance of preventive strategies targeting EBV to reduce the long-term burden of MS.
