Teenage bout of mono may serve as a big red flag for MS risk later

A history of infectious mononucleosis, often called “mono,” more than triples the risk of developing multiple sclerosis (MS), according to a new study.

While scientists have long suspected a link between the Epstein-Barr virus (EBV) and MS, these findings provide evidence that a documented case of mono serves as a significant red flag for the autoimmune disease.

The study, funded by Moderna and conducted in collaboration with the Mayo Clinic, tracked thousands of individuals over two decades. Researchers found that while MS remains relatively rare overall, the incidence rate was markedly higher for those who were infected with EBV during their youth.

Preventing these viral infections early in life could be a game-changer for public health.

“These results highlight the need for further research into ways to prevent infection with the Epstein-Barr virus,” Jennifer L. St. Sauver, PhD, study co-author at the Mayo Clinic, said in a press release. “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.”

The study, “Risk of Multiple Sclerosis Among Persons With Epstein-Barr Virus-Positive Mononucleosis: A Population-Based Study,” was published in Neurology Open Access. The work was funded by Moderna, a company developing vaccines to prevent EBV.

Recommended Reading

Feb. 16, 2026 News by Marisa Wexler, MS

Killer immune cells targeting Epstein-Barr virus may help drive MS

Tracking the link between EBV and mono

EBV is an extremely common viral infection, with almost every person infected at some point in childhood or adolescence. Most of the time, EBV infection doesn’t cause noticeable symptoms, but in some cases, especially in adolescents, the infection can lead to mono, which is marked by symptoms such as extreme fatigue and swollen lymph nodes in the neck.

There’s a great deal of evidence linking EBV with MS. In fact, many scientists think MS can only develop in people who have been infected with EBV. But because almost everyone has been infected with EBV and only a few develop MS, the relationship between the two remains incompletely understood.

Some previous studies have suggested that people who experienced mono, specifically, are at elevated risk of MS. However, these studies generally relied on self-reported mono history and insurance billing codes, which aren’t always reliable.

To address this issue, a team of researchers at Moderna and Mayo Clinic analyzed data from thousands of people who were followed from 1998 to 2022 as part of the Rochester Epidemiology Project, a large study collecting public health data that’s been ongoing since the 1960s.

The study included 4,721 people who had a documented diagnosis of EBV-positive mono, as well as 14,163 people who had no documented history of mono or EBV infection.

Over six years of follow-up, 0.17% of patients in the mono group developed MS. In contrast, 0.07% of those in the comparison group developed MS over a median follow-up of eight years.

Mathematically, that works out to 2.25 MS cases per 100,000 person-years in the mono group versus 0.77 cases per 100,000 person-years in the control group. Person-years is a measure that represents the number of participants in a study and the amount of time each person was followed.

Taking into account other factors that may influence the risk of MS, such as race and ethnicity, smoking status, number of co-occurring conditions, and socioeconomic status, participants with a history of mononucleosis had a 3.14 times higher risk of MS than those who did not experience mono.

The researchers said these results are “broadly consistent with previous studies that have reported an increased risk of MS in patients with EBV infection or [infectious mononucleosis].”

The scientists stressed that the data do not prove that mono leads to MS; they only show a significant association. More research is still needed into the connection between mono and MS. Nonetheless, these data support the idea that efforts to prevent mono are a viable strategy for MS prevention.

“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.