Mono infection associated with threefold higher multiple sclerosis risk

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, an official journal of the American Academy of Neurology.

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.

The study was supported by ModernaTX, Inc., which is developing vaccines to target multiple Epstein-Barr virus-associated conditions.