“EBV is an important factor for the development of the disease” in at least a subset of patients. The authors
A new study is revitalizing a long-simmering question about the role Epstein Barr virus (EBV) and other herpesviruses play in ME/CFS.
The herpesviruses have been studied on and off for decades in chronic fatigue syndrome (ME/CFS) and yet the research keeps coming.
Why? For one reason, reactivated latent viruses are just too juicy a possibility for an illness that often starts with an infection and is associated with damaged stress responses.
The symptoms found in ME/CFS are similar to those produced by “sickness behavior”: a process initiated by the brain during an infection that’s designed to keep us in bed to stop spreading i.
Plus enough positive study results have kept the herpesvirus theme alive in ME/CFS. While negative studies can be found, too many positive studies have kept this field of inquiry alive.
The Study
And now we have another positive result. A Bulgarian team (on behalf of the European Network on ME/CFS (EUROMENE)) assessed the prevalence of latent and active Epstein-Barr, cytomegalovirus and human herpes virus 6 in 108 ME/CFS patients and healthy controls (58 ME/CFS; 50 healthy controls).
Besides being larger than many past studies, this study went a step further than most past studies. Most studies have relied on more indirect measures such as antibody tests that assess whether an immune response to a virus has been raised.
This study, though, assessed antibodies and used a process called PCR to directly look for signs of herpesviruses (herpesvirus DNA) in the plasma. While several EBV antibody studies have had conflicting results, I was able to find only published two studies that have assessed active EBV infections using PCR. Neither found evidence of active herpesvirus infections in ME/CFS. One, however, was very small (n=20) and the other was 20 years old. In 2013, though, Ian Lipkin reported in a CDC talk that he failed to find direct evidence of herpesvirus infection in almost 300 people with ME/CFS.
Almost all of us carry latent or inactive herpesvirus infections in our cells and the are usually not a cause for alarm. Active herpesvirus infections, in which the pathogen is actively replicating and spreading from cell to cell through the blood, are another matter.
Results
The study did not find evidence of increased active cytomegalovirus or HHV-6 infections in the ME/CFS group. Two findings, however, suggested that active EBV infections were significantly more prevalent in the ME/CFS group. 
Almost 25% of the plasma samples from ME/CFS patients were positive for EBV DNA and almost 2/3rds of those patients also had high levels of antibodies (EBV‐CA IgG class antibodies) that have been linked with active infections. (This type of antibody latches onto an antigen on the capsid or shell of the virus. These particular antibodies fade quickly after the virus is vanquished from the blood.)
Using both serological tests and PCR, then, this study, then found evidence of an active EBV infection in about 20% of the ME/CFS patients tested. The authors asserted that this finding indicated “EBV is an important factor for the development of the disease” in at least a subset of patients.
The EBV ME/CFS Saga Continues
There are plenty of reasons to be concerned about an active EBV infection. Researchers are continuing to explore the role EBV plays in many serious illnesses including multiple sclerosis (MS), systemic lupus erythematosus (SLE), Guillain-Barre Syndrome, several cancers, rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, schizophrenia, and others.
In 2018, a remarkable study, which the lead researcher called “a capstone to a career in medical research” suggested that EBV is a kind of autoimmune accelerator that is turning on genes associated with autoimmune disease.
It’s not uncommon for EBV’s role in a disease to be unclear and so it is with ME/CFS. The ME/CFS field is littered with interesting and sometimes conflicting findings. We know that EBV – the main pathogen associated with infectious mononucleosis/glandular fever – is a common trigger for ME/CFS and several studies suggest that immune response to EBV may be lacking in some patients. Other studies, however, have found no evidence of an immune hole.
Over the past decade, Ariza and Williams at Ohio State University have methodically been making the case that a smoldering EBV infection is producing fatigue and other symptoms in a subset of people with ME/CFS. A recent study suggested that smoldering infection could be producing neuroinflammation. Two gene expression studies done ten years ago also suggested that EBV was turning on/off multiple genes in ME/CFS patients’ cells, and other interesting findings have been made.
This Euromene study was too small (n=108) to be definitive, but the dual testing approach (PCR and serology) elicited confidence in its results. Clearly, the EBV story in ME/CFS – like the EBV story in so many diseases – is not over. If an active EBV infection is present in a significant subset of patients the next question is what to do about it – and a recent study has produced some potentially good news on the treatment front. That blog is coming up next.
