Are Epstein-Barr and Chronic Fatigue Syndrome Linked?

Growing Body of Evidence

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"My doctor says I test positive for the Epstein-Barr virus, but that I don't need to be treated for it. When I go online, though, I find sites that say Epstein-Barr is linked to chronic fatigue syndrome. Is the connection true? If so, I'm concerned about going untreated. Is Epstein-Barr linked to chronic fatigue syndrome?"


Whether or not the Epstein-Barr virus and chronic fatigue syndrome are linked is still a gray area.

However, we have a small but growing body of evidence that there may be a relationship.

The Epstein-Barr virus (EBV) is a member of the herpesvirus family, and it's extremely common. Typically, it causes either no symptoms or a mild and brief illness, but the virus remains in your body, dormant, for the rest of your life. The vast majority of people infected with EBV do not develop chronic fatigue syndrome.

In some cases, EBV can cause mononucleosis (mono) in adolescents and young adults, and some research indicates that severe cases of mono may be more likely to result in juvenile chronic fatigue syndrome.

Some chronic fatigue syndrome experts believe that EBV or a reactivation of it can trigger the disease in adults who are already predisposed to it. Evidence supports a possible link.

A small body of research does support the virus' involvement, including a 2012 study (Lerner, PLoS One) suggesting that an EBV test could be used to identify a particular subgroup of chronic fatigue syndrome.

Another 2012 study (Agliari) hypothesizes that a persistent mono infection may throw the immune system out of balance, leading to chronic immune-system activation that results in chronic fatigue syndrome.

A 2014 study (Loebel) suggested that chronic fatigue syndrome may involve an impaired ability to deal with an EBV reactivation.

Doctors who believe in the link frequently prescribe anti-viral medications, such as Valtrex (valacyclovir) or Valcyte (valganciclovir), for chronic fatigue syndrome. These drugs show some promise in preliminary studies, but many doctors are unwilling to prescribe them until we have stronger evidence.

Agliari E, et al. Journal of biological dynamics. 2012;6:740-62. Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response?

Elgen I, et al. International journal of pediatrics. 2013;2013:270373. CFS in children and adolescent: ten years of retrospective clinical evaluation.

Katz BZ, et al. Pediatrics. 2009 Jul;124(1):189-93. Chronic fatigue syndrome after infectious mononucleosis in adolescents.

Lerner AM, et al. PLoS One. 2012;7(11):e47891. Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset.

Lerner AM, et al. In Vivo. 2007 Sep-Oct;21(5):707-13. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-sixth month follow up.

Lerner AM, et al. In Vivo. 2004 Mar-Apr;18(2):101-6. IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome.

Loebel M, et al. PLoS One. 2014 Jan 15;9(1):e85387. Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome.

Watt T, et al. Journal of medical virology. 2012 Dec;84(12):1967-74. Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibodytiters.

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