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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 ME/CFS

Herpesviruses have been studied in ME/CFS for decades. Few studies, though, have looked for direct evidence of active infection.

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

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.

Foremost Virus Hunter Finds Biomarkers, Few Viruses in Big Chronic Fatigue Syndrome Study

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.

Cell infected with herpesviruses

A cell infected with herpesviruses (green dots) (from National Cancer Institute)

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.

 

The Epstein-Barr Virus – Could it be Causing Neuroinflammation in ME/CFS?

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.

The Epstein-Barr Virus – Could it be Causing Neuroinflammation in ME/CFS?

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.

Epstein-Barr Virus May Be Turning On Pathogenic Genes in ME/CFS

 

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.

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44 Comments

  • Nikoli

    July 18, 2020 at 6:07 pm - Reply

    This is frustrating. My daughter did come down with Mono. (EBV starting it) When she was finally diagnosed with Mono, I had my own blood tested. Unlike about 90% of the population, I had never
    been exposed to EBV. My daughter was sick for 6 months, about the same time as most mono patients. But when it went longer, I told her “Honey, maybe you should see my doctor.” She is
    sometimes anti-everything I am, so she said “I DON’T have what you have, I WON’T have what you have!” I said “OK, I have stuff here for you to read, let me know if you want to.” And I left
    it there. About a month later, a small voice appeared on my phone: “Mom, I guess I should read that stuff.” We were going somewhere with she and my grandchildren. (She was formerly an Army MP, with associate vocabulary) On every page she read, she said “Oh, *****. this is me.”
    She saw my Rheumatologist, and yes, she had CFIDS. (Now of course, ME/CFS) Not long after, my son also came down with FM, and this was at a time when doctors kept telling us, “It’s not
    genetic.” Either we are one of the unluckiest families, or it is genetic.
    Unfortunately, my daughter’s illness progressed, first being told she had MS, now, it is more accurately diagnosed as Parkinson’s. She has fought to stay independent, but concedes soon she will need a wheelchair. She also came down, about midway through all this, with IC-
    Interstitial Cystitis. A drug that was found to help, Elmiron, now is being accused of several bad side effects, including damage to eyes or blindness!
    I am now 82, and have been ill since June 1981. I kept working for 9 more years in my aerospace work, but had to go on long term disability in May, 1990. And I didn’t quit until I left
    my work in an ambulance for the SEVENTH time. Nobody can tell me my illness, or that of my two adult children, is psychological!

    • Cort Johnson

      July 18, 2020 at 9:31 pm - Reply

      Wow…If you get exposed to EBV later in life it’s really hard to fight it off. Everybody should be intentionally exposed to it as children. It would save so much suffering. EBV is turning out to be quite a virus. Is it possible that it plays a major role in autoimmune diseases as well as ME/CFS and some cancers?

      Your family has really been through it! Good luck to you all. Maybe with COVID-19 attention will finally turn to the effects of postviral illnesses.
      We can’t get back the 40 years that you’ve had with this but maybe we can prevent it in others. Check out an action to double funding for ME/CFS.

      https://www.healthrising.org/blog/2020/07/16/historic-effort-nih-funding-chronic-fatigue-syndrome/

  • Paula Thornton

    July 18, 2020 at 6:41 pm - Reply

    Thank you for your continued effort in bringing forth this research. Clearly there’s not likely to be a ‘cure’ as it’s simply a matter of balance in naturally-occurring elements of our bodies. But understanding how to restore optimal human balance is critical. I’m grateful for many neutraceuticals that are improving my ability to function, and I could be happy with just functioning. But if thriving is possible…

    • Cort Johnson

      July 18, 2020 at 9:22 pm - Reply

      Congratulations on the improvement and good luck! Please let us know if you get to the thriving stage 🙂

  • Mary

    July 18, 2020 at 7:13 pm - Reply

    Curious. Since CoVid has taken front page and some of the patients go on so far to have lingering symptoms, I’m wondering if not only EPV but the HPV have a connection to lasting symptoms of ME/CFS or perhaps other chronic autoimmune disease. I’ve been ill for more than 2 years and my symptoms range throughout every body system , counting likely 100 + symptoms. What are your thoughts and will there be more research into the long term chronic health issues of viruses on the body? I’d love to be a part but I’ve been left so disabled by this not diagnosed illness, that I’ve run out of money and insurance and not only am in isolation because I feel so sick everyday, but now know it would be a death sentence to go outside my door without a hazmat suit… LOL… Really it’s not at all funny but humor is all that gets me through this mystery illness that has wreaked havoc all through my body.

  • Di

    July 18, 2020 at 7:57 pm - Reply

    So in a blood test for EBV, the norm should be zero. My lever is always between 1700-1800. Does this mean ongoing EBV infection? It feel like I’ve had a full blown flu for years.

    • Cort Johnson

      July 18, 2020 at 9:20 pm - Reply

      It’s actually pretty rare for anyone to get a PCR test – which looks for EBV DNA in the blood. Since not many doctors use it I assume you had a serological or antibody test done (???) which measures the number of antibodies to EBV present. Several of these are possible – IgM and IgG antibodies to viral capsid antigen (VCA IgM, VCA IgG) and Epstein-Barr nuclear antigen (EBNA). Unfortunately I don’t see an assessment of levels. I believe that high Anti-VCA IgM, Early antigen (EA) antibodies are indicative of an active infection.

  • Julia

    July 18, 2020 at 7:58 pm - Reply

    Why do the researchers use a plasma EBV PCR test rather than a whole blood EBV PCR test. Can both be used?

    • Cort Johnson

      July 18, 2020 at 9:05 pm - Reply

      Here’s what the HHV-6 Foundation says about whole blood vs plasma for HHV-6. Both can be used but whole blood appears to be better.

      https://hhv-6foundation.org/patients/hhv-6-testing-for-patients

      PRC Test on Plasma – HHV-6 is never found in plasma or serum unless there is an acute infection (or the individual has ciHHV-6). However, the absence of HHV-6 DNA in the plasma/serum does not mean that there isn’t a low-level persistent infection in the tissues (e.g. heart, thyroid, brain). Any positive test result should be repeated with a quantitative test.

      Quantitative PCR on Whole Blood – If the viral load is >200 copies per ml or 20 copies per microgram of DNA then this is an active infection.

  • Winston

    July 18, 2020 at 8:15 pm - Reply

    Sheesh, what a cliffhanger!

  • Helen M

    July 18, 2020 at 9:21 pm - Reply

    I read a study on covid -19 patients that sais approx 50% were found to have active EBV infections. I will find the link.

    • Cort Johnson

      July 18, 2020 at 9:58 pm - Reply

      Interesting! One of the hypotheses is that these viruses are reactivating EBV and EBV is doing the damage.

  • Helen M

    July 18, 2020 at 9:23 pm - Reply

    https://www.researchsquare.com/article/rs-21580/v1

  • Nancy B.

    July 18, 2020 at 10:37 pm - Reply

    I’m having trouble making sense of my EBV virus lab results;
    VCA IgG, positive > .9, my results 5.36 ISR
    EBNA IgG, positive > 1.1, my results 3.53 ISR
    VCA IgM and EA IgG are both negative
    All done by ELISA method with overall results being ‘past EBV infection.’

    So are my numbers high or low in the grand scheme of things and do they correlate to my past antibody response or current levels or perhaps some viral particles still lurk or may be semi-active?

    Anybody know?

    This reminds me of the Dr. Henderson article I posted recently where mere parts of viral proteins can linger and affect the immune response (and perhaps the genes) as well. Also regarding Covid, I read a very interesting article about how the serology tests (antibodies) are most pronounced for about two weeks after clearing the infection and then for some people they almost completely disappear, usually after about 3 months. (This means for some, if you wait too long you may wrongly test negative for Covid because you are one of those people whose antibodies disappear quickly). Everybody seems to be a bit different and some mount a very vigorous immune response and others not so much. In addition to that, some people’s immune response lasts much longer than others and for some, it doesn’t much last at all…

    Considering these Covid antibody results, could the fact that EBV alters some of the genome (as it is likely Covid does too), account for the fact that ME/CFS can present (ME/CFS subtypes) so differently in individuals because of the variations in each person’s DNA, and their immune response, even though the original cause (in this case EBV) is the same?

    I ask these because of a very interesting Covid article about the difficulty of determining the true beginning or ending of a Covid infection because some tests will pick up enough viral fragments as to indicate that the infection is still active. Sometimes these tests will waver between indicating non-infection and then later infection and then back again. This has caused some consternation amongst virologists about whether people can become infected twice or if the infection can remain in the body much longer than we think, or even if it can go dormant and then revive.

    I’m sorry if I’m carrying on, but sitting here in quarantine, my research has gone into some kind of cabin fever hyperdrive…

    One last observation regarding another Covid research article, points out that some researchers in Paris have found that abnormal expression of IL-6 and TNF-a cytokines seem to indicate a more serious infection with Covid. I looked up some comparatives with ME/CFS, and the study by S.F. Milrad identifies those same cytokines in people with ME?CFS–although other research results disagree.

    This is like a fence of research data that will eventually corral the causes of our disease…I hope!

  • Nancy B.

    July 18, 2020 at 10:46 pm - Reply

    P.S. Regarding those wavering Covid test results–they could just be not very accurate (or overly sensitive) tests too–something that could be true for EBV tests as well.

  • Andrea F.

    July 18, 2020 at 11:01 pm - Reply

    Hi…I’m a person who is in that subset. I got Mono in 2010 and again in 2014 and was diagnosed with recurring mono, HHV-6 and ME/CFS. It’s brutal. I pray for more studies. Since I was diagnosed in 2014 I’ve developed Sjorgren’s Syndrome too. On top of all that I have Psoriatic Arthritis, Fibromaylgia and a myriad of other neuro issues…including small fiber neruropathy.

    • Cort Johnson

      July 19, 2020 at 12:53 am - Reply

      You have to wonder if EBV could be behind that. It is just so much harder to fight off when you are older. Hopefully the EBV autoimmune finding mentioned in the blog will spur more research. Hopefully COVID-19 will spur a ton of research on what happens to people with post-viral illnesses.

  • Betty Mekdeci

    July 18, 2020 at 11:06 pm - Reply

    Did I miss something? I don’t consider a study with 58 ME/CFS patients and 50 controls to be a large study.

    My doctor, who decided to retire in the middle of this pandemic was constantly running tests of EBV, CMV, HHV6, HHV1 and 2 and other herpes viruses like zoster every 2-3 months. I had elevations in many of them. He became very irritated with me when I refused to take antivirals (tried them, did nothing for me). When various herpes viruses become elevated, it indicates there is a problem with immunity.

    The famous bubble boy died when he received a stem cell transplant from his sister. She had a mild case of EBV in childhood, but this ran rampant in the child with no immune system triggering the lymphoma that killed him.

    More research should be done on the immune status of ME/CFS patients.

    • Cort Johnson

      July 19, 2020 at 12:50 am - Reply

      Since we so rarely see studies in the three figures it seems pretty darn large to me – at least relative to most studies in ME/CFS.

  • val66

    July 18, 2020 at 11:25 pm - Reply

    >”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.”

    Any hint or small preview to the teased treatment? What is it?

    • Cort Johnson

      July 19, 2020 at 12:48 am - Reply

      🙂 Coming up soon.

  • Judy Acton Ayala

    July 19, 2020 at 12:37 am - Reply

    How INTERESTING. The Truth no one knows or wants to hear simply because of the source, is that this “new” information actually came from Anthony William Medical Medium starting DECADES ago (at least 35 years ago). The reason it is now slowly seeping into western medicine is because of the thousands of doctors who have been using MMs books to actually HEAL their patients. Doctors literally call MM books “advanced medical science.”

    The Truth is that ME/CFS and Many other so-called “auto-immune” diseases, as well as Many, Many other maladies are caused by one or more of the over 60 strains of EBV! ME/CFS is Stage Four EBV; there are four stages. Today’s testing can’t detect EBV in the body, as it hides deep in the organs and tissues. It starts in the blood, moves to the liver, then thyroid, then nervous system (this is from memory—I’ve read all his books as I’ve been healing with them for two years and counting, so I may have that a bit wrong, but I’m pretty sure that is correct).

    Anyway, I’m thrilled to be sharing this knowledge with you!!!! There’s soooooooo much more to say here, as the MM books turn people into health experts! But I’ll instead guide you to his website. ALL his materials are FREE, except the books, of course, but he’s always telling people to get them from the library! Anthony is never about himself, and never about making money. He’s not invested in or sponsored by any of the supplement companies he recommends on his site.

    It needs to be said there is mostly Lies and Misinformation about him on the Internet, so be aware of that. Big Pharma and Big Industry will stop at nothing to try to discredit him. They have even hired sleuthy trolls to realistically claim they got worse on MM. They are super threatened by him because he tells the Truth via the Spirit of Compassion and they know it, believe me, they know it. They also know too well their role in how and why EBV is so rampant. Did you know that EBV used to be “the” friendliest virus in the body? That it was a warrior in fighting off bad guys in the body? Do you know why and how it was forced to turn to the dark side, so to speak? Read his books! Listen to his recordings! They are guaranteed to Blow Your Minds. They sure did and do mine!!

    http://www.medicalmedium.com

  • A Shadow of Yesterday

    July 19, 2020 at 1:20 am - Reply

    Cort: I just got elevated to Mayo Clinic. Previous labs a couple years ago one number was almost 500 indicating reactions of EBV. IDC doc indicated I will continue to have flares and it can reactivate… so I am hoping this will be a gem of info for them to disect. I just saw my rheumy on Thurs and in 24 hours Mayo contacted me. Crossing my fingers they can find something useful…..Would my Ancestry dna info and 23&me health dna info be of any help to them at all?

  • Nancy

    July 19, 2020 at 1:29 am - Reply

    If anyone wants to know about the numerous Herpetic Viruses and all related illnesses read Anthony William’s series of books…all autoimmune is misdiagnosed in allopathic and naturopathic medicine…truth is The immune system never attacks the body it is attacking the active pathogens triggered in ones body creating all manner of chronic illness. 6 New York bestseller books With all the answers and protocols for finally Healing….Book 1 Secrets Behind Chronic and Mystery Illness and how to finally Heal. I have been on the protocols for 42 months. 95% symptom free from 51 symptoms/diagnoses….CFS, Lyme Disease, Lupus, Menieres, Hashimotos and hypo thryroid, migraines, frozen shoulder, restless leg syndrome, heart palps, high cholesterol, high blood pressure, high A1c, numbness and tingling, chronic sinitus, short of breath. Tinnitus to name a few

  • Barbara Dimmick

    July 19, 2020 at 3:02 am - Reply

    I have been tested repeatedly for EBV over the years, with never a positive result. The beginning of my ME was waking in my uncle’s guest room in Brooklyn, dripping in sweat, and so dizzy with high fever that I had to crawl to the bathroom to keep from falling.Over the next horribly acute 3 to 4 weeks, I was tested for many things, with two doctors finally deciding to call it “classic influenza.” Perhaps that was it; but after the first month, my fever (now low grade) and the god awful weakness and pain dragged on for at 16 more weeks before I had a normal temp again, even for a few hours. I wonder sometimes what hit me so hard.

  • Lori England

    July 19, 2020 at 10:24 am - Reply

    My ME CFS appears to have been triggered by a reactivation of EBV caused by an infection with the Human Parvo B19 virus which causes a common childhood illness known as Fifth Disease. Initially, I tested positive for an active infection of Human Parvo Virus B19 which had been ordered by a doctor at a local urgent care facility. Why he would even test me for this virus, I’ll never know, but I’m grateful that he did. Later, after my illness continued, a new PCP ordered more blood work and it showed I had a reactivated form of EBV. My EBV titers remain elevated to this day. The University of Minnesota has been working for several years now to develop a vaccine against EBV/Mononucleosis called The Mono Project. They recognize how dangerous and widespread the EBV virus is.

  • Karen

    July 19, 2020 at 12:10 pm - Reply

    Why not look for EBV in the salivary glands and the lymph nodes in the neck, which are often tender in this illness? Of course blood is much easier to sample but given the frequency of sore throats and swollen lymph glands, that seems like the best place to find viral pathogens.

  • Dana

    July 19, 2020 at 12:12 pm - Reply

    I’ve always felt that EBV was the cause of my woes. Before I was diagnosed with ME/CFS I would get viral thyroiditis episodes that would last 6 months and I would feel really run down. I would also get elevations in my liver enzymes and was put through every possible liver test including a very painful biopsy.

    My thyroid has been removed but I still get elevations in liver enzymes. Recently I went off the antiviral I was on and surprise my enzymes went even higher. So I went on 2 antivirals and even more surprising is that my liver enzymes have never been better.

    Unfortunately I don’t feel that great because several Coxsackie B viruses are reactivated again. Like Covid, antivirals won’t work for that. I’m trying to figure out what I can do for that.

  • David Fontaine

    July 19, 2020 at 7:29 pm - Reply

    Here’s another one for “The List of Things That Make You Go Hmmmm….”

    For those who think there may be an environmental component to their illness – or, know there is, as Lissa and I do – you may find this article of interest. It’s a 2015 paper from an Oxford cancer research journal, showing that Aflatoxin B1 can reactivate EBV.

    The mycotoxin aflatoxin B1 stimulates Epstein–Barr virus-induced B-cell transformation in in vitro and in vivo experimental models –
    https://academic.oup.com/carcin/article/36/11/1440/372011

    Clearly, this may not be the only thing that can reactivate EBV, but it sure is an interesting one, given the frequency of water damaged buildings full of molds like Aspergillus. Lissa and I both tested highly positive for Aflaxotin, plus a few other mycotoxins, in our early Realtime Labs tests.

    In my mind, if they’ve not yet done so, anyone showing active EBV might want to consider mycotoxin urinalysis, particularly if they’re showing a broad set of the common symptoms of mold illness – ex. per Shoemaker.

  • Cort Johnson

    July 19, 2020 at 7:41 pm - Reply

    Hi Mary.

    I believe that post-viral illnesses are about to get a whole bunch more attention.

  • Forebearance

    July 19, 2020 at 7:47 pm - Reply

    I had EBV for the first time at age 28. Three different blood tests from three different doctors confirmed it. After six months I had the classic ME/CFS symptoms. Three years into my illness, as I was in the process of being diagnosed, a doctor told me I had never had EBV!! Apparently I didn’t have any long-term antibodies to it by that point. It has always puzzled me.

    I would sure like some answers!

  • Sara

    July 19, 2020 at 8:01 pm - Reply

    Thank you for posting this, I’ve been using MM protocols/ diet to heal from EBV which caused fibromyalgia, vertigo, tinnitus, CBS etc for years! Antony Williams is a saint and the only one who gives clear answers to a very murky chronic illness riddle!

  • barbara bottner

    July 19, 2020 at 9:08 pm - Reply

    Regarding Anthony Williams, one of his strong recommendations is daily, organic celery juice. I’ve been on it a year, almost every single day. For six months, I was in a great state; the last six I’ve been sick again. I am off gluten, dairy for many years. I got ME/CFS over thirty years ago. I’ve always had titres for EBV when tested. For me, the best treatment is glutathione pushes.

  • SM

    July 19, 2020 at 11:47 pm - Reply

    Nancy B: I am a doctor of physics with ME/CFS, not a doctor of medicine, but I have this information to share with you about my case. My conclusion about your results: you have a stewing EBV infection like I did, not strong enough to show early antigens and an active infection, but too weak to get rid of the EBV in your body. Your numbers are not as high as my numbers were, but high is still high.

    Back in 2012, I had an EBV panel done when I was having ME symptoms but not horrible, but the results were in another form: Ab VCA IgG (old infection) = 1:320 (should be lower than 1:10). VCA IgM (active infection) = less than 1:20 (normal is less than 1:20). EBNA Nuclear antigen ACIF = 1:40 (normal less than 1:10) which indicated that I had an active infection 3-4 weeks prior. EBV Early antigen IgG = 1:80 (normal is less than 1:10), which indicated that I was fighting EBV but not at an acute level. My results were mixed, which indicated that I had a stewing infection that wasn’t big enough to trigger a full blown antibody response.

    My next test was in 2013 when I had a relapse of ME/CFS. These results agree with your results, in the same units. Early antigen IgG: normal (less than 0.2). Ab VCA IgG: greater than 8.0 (normal is less than 1.0). EBNA Nuclear antigen IgG: greater than 8.0 (normal less than 1.0). No IgM test (active infection) was done, probably because the EBV Early antigen came back negative. So these results showed pretty much the same as the 2012 results, an old infection.

    Retesting in Nov 2014 (1.5 years later) showed these results, in yet another set of units: Early antigen IgG = normal (less than 9.0). Ab VCA IgG = greater than 600 (normal less than 18). EBNA Nuclear antigen IgG = 237 (normal is less than 18). Again, it looked like an old infection but with huge IgG antibodies, which should not be happening.

    My doctor, who was brilliantly putting the pieces together, told me that my body was NOT fighting EBV properly, considering that my IgG antibodies were still very high even though there was supposedly not an active infection. I was one of his first patients to try off-label Viread (the entry-level HIV/AIDS medication) because it was an anti-retroviral medication, and EBV is a retrovirus. I was hesitant, of course, but I was desperate to feel better.

    In 2017 after a few years on the Viread, these were my test results: Early antigen IgG = less than 9 (normal less than 9). Ab VCA IgG = 480 (normal is less than 18). Nuclear antigen IgG = 163 (normal less than 18). So there had been some modest improvement in the numbers. But even more profound was that I felt better, my energy was better, and my brain function was better. Was the Viread going after stewing EBV, or some other retrovirus? Unknown, but likely both.

    I have continued on the Viread all this time, and I believe that my numbers would be even lower if I retested now. I guess it’s time to check my numbers, to see what’s happening today. I hope this helps.

  • Betsy

    July 20, 2020 at 12:54 pm - Reply

    Thanks for the suggestion re Viread SM. I have not only extremely high antibodies but also early antigen, done at Stanford years ago but my docs in CO don’t think anything of it – one says she no longer even tests for it because so many of her patients had high numbers but were totally well. The high antibody count they contribute to a good immune system.

  • dejurgen

    July 20, 2020 at 2:21 pm - Reply

    Interesting…
    This could link to your recent Healthrising mucosal-genes-chronic-fatigue-syndrome blog.

    According to Wikipedia(Epstein–Barr_virus)
    “EBV can infect different cell types, including B cells and epithelial cells.”
    “Once EBV enters the cell, the viral capsid dissolves and the viral genome is transported to the cell nucleus.”
    “The lytic cycle, or productive infection, results in the production of infectious virions. EBV can undergo lytic replication in both B cells and epithelial cells. In B cells, lytic replication normally only takes place after reactivation from latency. In epithelial cells, lytic replication often directly follows viral entry.”

    Mucus and epithelial cells are very closely related. If, according to the recent genetic study, the mucus layer in near 80% of the ME patients is a LOT thinner due to a gene variation AND the epithelial cells underneath it indeed get a lot more irritated / infected / inflamed… then we may be in trouble:

    EBV is known to be an opportunistic pathogen, reactivating a lot more in the presence of another infection. This could interweave one of two storage sites of EBV together with a zone of near constant inflammation due to this genetic thin mucus variation. The gut is made of epithelial cells too so there EBV infected gut epithelial cells could be chronicaly inflamed AND be barely separated from the gut bacteria.

    Now add the last quote “In epithelial cells, lytic replication often directly follows viral entry.”.
    So, in the gut infected epithelial cells seem to be less likely to go EBV-replication dormant. With supposed chronic gut inflammation and thinned mucus layers, I can imagine that many gut epithelial cells have weakened cell walls possibly easing access of the virus to the epithelial cells.

    Once the virus enters an epithelial cell “In epithelial cells, lytic replication often directly follows viral entry.”. As long as that epithelial cell is still alive enough, that should have an increased chance to produce and leak new viruses in and near the gut wall and other epithelial cells.

    => Could the combination of these two pieces of the puzzle help explain things?

  • dejurgen

    July 20, 2020 at 2:41 pm - Reply

    When speaking of EBV lasting life long in the body and reactivation, I see an awful lot more discussion about the virus residing for life in the B-cells. Very few AFAIK is said about the virus living for life in the epithelial cells. So maybe a healthy person has few EBV infected epithelial cells?

    If so, that could make sense. (Gut) epithelial cells clearly aren’t immune cells, so EBV infected epithelial cells might have more trouble fooling the immune system. Also, gut cells and epithelial cells are fairly short lived. A Havard website called bionumbers says “Autoradiographic studies indicate that the life span of a typical intestinal epithelial cell is only 3 to 4 days.” That’s really short.

    During replication of cells the virus, not being tightly integrated with the human DNA, does not necessarily copies into the new cells. So at each renewal of the epithelial cells their *might* be a small chance to reduce the percentage of epithelial infected cells. That over a long time *could* reduce the percentage of infected (gut) epithelial cells to near zero IMO.

    At least, that is for healthy people with normal mucus thickness layers and no chronic gut inflammation. Both these factors could increase the amount of gut epithelial re-infection rates just enough to *increase* the percentage of EBV infected (gut) epithelial cells once a certain threshold is reached *IF* I understand and estimate this well.

    Now how would the age of EBV infection relate to this? Children and young adults have far higher cell division and replacement rates and growth hormones as far as I know. That could influence the above equation. If the epithelial cells are replaced or do replicate before enough are infected, this “reproduction rat R” similar to what is so important in the current Covid pandemic, might just drop below 1 rather then being higher then 1. And as we learned during this pandemic, that rate being just below or just above 1 long term does make a world of difference: extinction of local infections versus global explosion of infections.

    Interesting to note: during pregnancy the mothers placenta does produce a lot of growth hormone. That *might* be another factor temporarily improving symptoms in pregnant women.

  • dejurgen

    July 20, 2020 at 2:50 pm - Reply

    With the above ideas, there is a problem that the study only did found about 25% of ME patients had a *recent* EBV reactivation. So it seems that the *hypothetical* mechanism of EBV and mucus gene mutations interacting would only hold for a small-ish subgroup.

    To partly counter this idea:
    1) There are other herpes viruses that are opportunistic pathogens and could pull a similar prank on us.
    2) *recent* is an important word here. How recent does the re-activation need to be in *ME patients* (with possibly increased immune activity against this specific pathogen) in order to be shown in these tests? And how long lasts the nefarious effect of a single (gut epithelial) re-activation in ME patients?

    => It would be very interesting to do a follow up and test the entire group at regular intervals to see if they have markers of recent EBV re-activation. Many more patients might have one or several re-activations in the course of a year then this 25%.

  • Mary

    July 20, 2020 at 8:50 pm - Reply

    I agree Cort ! There are so many similarities reading all these comments. FINALLY I hope all of our symptoms won’t be chalked down to “anxiety psychosomatic issues” when a root diagnosis can’t be determined. Sad to say this happens so much to women as studies have shown. In the meantime the suffering goes on and on and on! Thank you for bringing attention to the connections together here. I look forward to reading more of you emails.

  • Kristina

    July 20, 2020 at 10:22 pm - Reply

    If the EBV-EA (EarlyAntigen) is +positive, you have an Acute Current Re-Activated infection. It is only fleetingly positive at the beginning of infection and is hard to catch positive as most people almost immediately begin to convalesce. If yours is positive every time doc tests, you have a Chronic Active Infection. This is usually the case in ME/CFS.
    @Nancy above, since you didn’t mention it, your doc must not have run that test & it’s the most Important one to tell what’s really going on

  • Kristina

    July 20, 2020 at 10:45 pm - Reply

    If the EBV-EA (EarlyAntigen) is +positive, you have an Acute Current Re-Activated infection. It is only fleetingly positive at the beginning of infection and is hard to catch positive as most people almost immediately begin to convalesce. If yours is positive every time doc tests, you have a Chronic Active Infection. This is usually the case in ME/CFS.
    @Nancy above, since you didn’t mention it, your doc must not have run that test & it’s the most Important one to tell what’s really going on
    @David, my ME/CFS was low grade but really skyrocketed when I lived in water damaged building, too.
    Like some of you above, I have severe Small Fiber Neuropathy & diagnosed Function NK-Cell Deficiency
    I really believe (as Stanford specialists tell me) that ME/CFS is caused by an as-yet-undiscovered Virus & those of us with immune deficiency have the worst cases

  • Riv

    July 21, 2020 at 2:56 am - Reply

    Familial CFS. Treatable. See one reason why CFS is diagnosed in families sometimes.
    https://pmj.bmj.com/content/postgradmedj/73/859/311.full.pdf

  • Jerry

    July 23, 2020 at 6:46 am - Reply

    Many more studies supporting this here…
    http://researchfraud.com/cfs-opportunistic-infections/

  • Jasmine

    August 12, 2020 at 8:08 pm - Reply

    Very interesting and thanks for sharing it together with the Spirolonolactone article! It does look like this EBV is very persistent and my antibody levels are still high after 2.5 years on antiviral. My EBV VCA IgG and EBNA was >600 when first diagnosed and then came down after Valtrex and then back up again. My EA (early antigen) was negative in the beginning then got positive but then got negative again after I switched to Famvir.