Epstein-Barr Virus and MS Risk: New Link to Mono Found in Study

People who had infectious mononucleosis — a contagious disease for which the Epstein-Barr virus (EBV) is the leading cause — had a higher incidence of multiple sclerosis (MS) in the 10 years following diagnosis compared with individuals not diagnosed with the virus, a study found.

This link was particularly strong for patients diagnosed with infectious mononucleosis, commonly known as mono, between the ages of 14–20.

These findings further strengthen the link between EBV and MS that has emerged over the last several years.

“These data could improve our understanding of the development of MS and possibly help to find novel therapies,” the researchers wrote.

“Future preventive options could include EBV vaccination,” the team noted, particularly for those who may already be genetically susceptible to MS — specifically, relatives of multiple sclerosis patients.

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The study, “Infectious mononucleosis is associated with an increased incidence of multiple sclerosis: Results from a cohort study of 32,116 outpatients in Germany,” was published in the journal Frontiers in Immunology. 

The link between Epstein-Barr and MS

MS is an autoimmune condition thought to arise from a combination of genetic and environmental factors. An increasing number of studies have emerged over the last several years supporting a role for EBV as a major environmental risk factor for MS.

Epstein-Barr is one of the most common viruses worldwide, affecting most people at some point in their lives. The virus is the leading cause of mono, accounting for more than 90% of cases — though most people who are infected with EBV won’t have any symptoms and may never know they had it.

After infection, the Epstein-Barr Virus remains dormant inside B-cells, an immune cell type implicated in MS.

A study published earlier this year further established the long suspected link between EBV and MS. Involving more than 10 million young adults in the U.S., the study demonstrated that having the Epstein-Barr virus — as determined by the presence of antibodies against it in the bloodstream — increased the risk of developing multiple sclerosis by 32 times. Notably, a similar link was not observed with other viruses similar to EBV.

Despite these findings, the causal relationship between EBV and MS “is still discussed controversially,” the researchers noted.

Thus, to further examine the connection, a team of scientists in Germany evaluated the incidence of MS over a 10-year period after a mono infection in more than 16,000 German patients. The team compared that rate with those seen in patients who had no mono diagnosis.

Cases were identified from the Disease Analyzer database, which contains medical and demographic data related to outpatient visits at general medical practices in Germany.

A total of 16,058 patients who had been diagnosed with mono between December 2018 and January 2000 were identified from the database. Of note, a mono diagnosis could have been classified as due to EBV or another unspecified cause. Based on the expectation that mono is largely caused by EBV, most of these cases would likely be associated with the virus.

An equal number of control participants — matched to infected patients in regards to age, sex, and frequency of doctor visits, but without the mono diagnosis — were also included in the analysis.

Participants had a mean age of 32 years and 58.6% were female. While none had an MS diagnosis at the study’s start (baseline), 5.7% of individuals with infection and 5.6% without it had another autoimmune condition.

Within 10 years of a mono diagnosis — or a randomly selected doctor visit in the case of individuals not diagnosed with mono — 0.49% of patients with mono and 0.26% of those without it were diagnosed with MS.

Researchers found that the MS incidence rate for those with mono was 22.6 per 100,000 person years — a measurement that accounts for both the number of people in the study and the amount of time each person was followed. Meanwhile, the incidence rate among those without mono was 11.9 per 100,000 person years.

Overall, having a previous mono diagnosis was significantly associated with a higher incidence of MS, regardless of the presence of other autoimmune conditions.

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Higher risk for mono patients ages 14–20

“Our data reinforce previous research findings that EBV plays a causal role in the pathophysiology [disease mechanisms] of MS,” the researchers wrote.

When data were stratified by age group, only mono infection in patients between ages 14–20 was significantly linked to MS, with the association diminishing with increasing age.

“To the extent that there is a causal relationship between EBV infection and MS incidence, it appears to be particularly effective at a young age,” the researchers wrote.

The team noted that the exact mechanisms by which EBV might lead to MS aren’t established, nor are other factors — genetic or environmental ones — that may interplay with EBV to cause disease.

However, they noted that, in certain conditions, “EBV seems to trigger specific biological changes that are required for the development of MS.”

One study limitation noted by the researchers was that lifestyle factors, like smoking or socioeconomic status, which could influence MS risk, were not available in the database. Further, because the study was not based directly on EBV antibodies, but rather a clinical diagnosis of mono, it cannot be ruled out that some patients in the control group could have had a prior, undiagnosed Epstein-Barr virus infection.

“The very fact that the results in our study are nevertheless significant shows, that the association shown between EBV and MS is strong,” the researchers wrote.