Active Epstein-Barr Infections Found in Large ME/CFS Study

"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 of Epstein Barr Virus and other herpesviruses in ME/CFS.Herpesviruses just never seem to go away, in the ME/CFS field. They've 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 too juicy a possibility for an illness that often starts with an infection. ME/CFS also produces symptoms similar to those  produced by "sickness behavior": a process initiated by the brain that's designed to keep us in bed to stop spreading an infection. 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 inquiry from fading.

The Study

Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic еncephalomyelitis/chronic Fatigue Syndrome Evelina Shikova ^1 2, Valentina Reshkova ³, Аntoniya Kumanova ¹, Sevdalina Raleva ¹, Dora Alexandrova ², Natasa Capo ^4 5, Modra Murovska ⁶, European Network on ME/CFS (EUROMENE J Med Virol. doi: 10.1002/jmv.25744.

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 has been raised to determine whether active herpesvirus infections are present. 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.http://simmaronresearch.com/2013/09/foremost-virus-hunter-finds-biomarkers-few-viruses-chronic-fatigue-syndrome/If pathogens are in a latent state they should remain in the cells and not be present in the blood. Almost all of us carry latent or inactive herpesvirus infections in our cells. They are 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 - perhaps similar to those found in infectious mononucleosis/glandular - were significantly more prevalent in the ME/CFS group.Almost 25% of the plasma samples from ME/CFS patients were positive for EBV DNA.  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.)The study didn't find evidence of active HHV-6 or CMV infections. (Some researchers, however, believe that a smoldering infection that this type of research wouldn't detect may present in a subset of ME/CFS patients. Also low level HHV-6 infections in the organs may not  show up in the blood.  Nor did the study assess the early EBV proteins that Williams at Ohio State University has been finding in ME/CFS.)Using both serological tests and PCR, this study provided a robust finding 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's plenty of reason 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. http://simmaronresearch.com/2019/07/epstein-barr-virus-neuroinflammation-chronic-fatigue-syndrome/The EBV saga in ME/CFS 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. Several studies also suggest that immune response to EBV may be lacking in some patients; i.e. some people with ME/CFS appear to have trouble fighting it off.  Some studies have found a paltry antibody response to the virus. 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.http://simmaronresearch.com/2019/07/epstein-barr-virus-neuroinflammation-chronic-fatigue-syndrome/

The Autoimmune Virus?

On a broader front, a 2018 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 - an interesting finding given the possibility of an autoimmune subset in ME/CFS.   Two gene expression studies done ten years ago suggested that EBV was turning on/off multiple genes in ME/CFS patients cells.http://simmaronresearch.com/2019/06/epstein-barr-virus-ebv-genes-chronic-fatigue-syndrome/ This Euromene study was too small (n=108) to be definitive, but the dual testing approach (PCR and serology) provided 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.With regards to that question, a recent study has produced some potentially very good news on the treatment front. That blog is coming up next.