How a coronavirus study shed light on Epstein-Barr Virus reactivation in ME/CFS.
Of all the opportunities the SARS-CoV-2 virus has inadvertently opened up for chronic fatigue syndrome (ME/CFS), this one might be the most creative thus far. This study highlights the news ways researchers are using the long-COVID pandemic to better understand ME/CFS.
That Epstein-Barr Virus – it can really do things… Check out an EBV-infected cell (from Wikimedia Commons)
This Swedish study, “Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome“, contrasted the immune response between people with ME/CFS and healthy controls, before and after they came down with mild cases of COVID-19.
The question was whether a pretty darn potent virus would produce a different antibody response in immune-challenged people with ME/CFS. Because this study assessed the antibody response in people with “mild” infections (i.e., people who were not hospitalized), it can tell us how even milder infections can potentially tweak the immune response.
Antibodies – which are produced by B-cells – play a major role in the adaptive immune response that takes several days to kick in but is largely responsible for eradicating pathogens. They also can play a major role in autoimmunity when antibodies – seeking to attack a virus – attack a human tissue instead.
Because pathogens trigger the production of a range of antibodies, assessing which antibodies can tell us the nature of the response. In this case, the researchers were particularly interested in antibodies to herpesviruses and their possible reactivation during the COVID-19 infection. Epstein-Barr virus (EBV) and other herpesvirus reactivation have been found in spades in people with severe coronavirus infections, and EBV reactivation has been associated with long COVID in a couple of studies.
EBV certainly has a long history in ME/CFS. Studies in the mid-1990s, including one from the CDC, suggested ME/CFS was, at least in part, “chronic infectious mononucleosis” or “chronic mononucleosis syndrome“. Even Stephen Straus – not often viewed as friend to ME/CFS – at one point penned a paper on “The chronic mononucleosis syndrome“. In 1998, Peter White concluded that infectious mononucleosis/glandular fever was a particularly strong trigger of ME/CFS and believed it was probably responsible for around 3,000 new cases of ME/CFS a year in the U.K.
Recent studies suggest EBV may be causing neuroinflammation, turning on pathogenic genes, and triggering the production of autoantibodies in ME/CFS.
The researchers assessed IgG, IgM, and IgA antibody responses to the coronavirus, to six herpesviruses (HHV1-6, HSV1, HSV2, VZV, EBV, CMV, HHV6A), and to a human endogenous retrovirus-K (HERV-K) before and 3-6 months after COVID-19 in 95 people with ME/CFS and 110 healthy controls.
Results
“Our findings demonstrate that SARS-CoV-2 infection, even in its mild/asymptomatic form, is a potent trigger for the reactivation of latent herpesviruses and endogenous retroviruses. This is particularly relevant for individuals suffering from ME/CFS.” The authors
Coronavirus
High rates of an asymptomatic coronavirus infection (42% ME/CFS; 31% healthy controls) puts in stark relief the idea that many people with ME/CFS who had no evidence of an infectious trigger may, in fact, have had one. Symptoms, in other words, are not required.
Interestingly, this study showed that none of the asymptomatic healthy controls who’d been infected with the coronavirus displayed antibodies to the coronavirus in their plasma (blood) – only in their saliva. That suggested that their first line of immune defense – in the nose and mouth – probably knocked out the coronavirus before it got into their bloodstream.
Interestingly, the immune systems of the people with ME/CFS appeared to jump on the virus more quickly as many more people with ME/CFS had antibodies in their saliva, but not their plasma, compared to the healthy controls. This “hyper-inflammatory response” to a pathogen appears to represent an immune system that was on alert and ready to pounce on evidence (such as a pathogen-associated molecular pattern or PAMP) of an invader.
The authors suggested that the immune cells in ME/CFS exist in a state of senescence – something like a state of torpor – when they have problems replicating. We’ve seen something like this before in the suggestions that our cells exist in a hypometabolic, or Dauer, state and/or that NK cells and T-cells exist in a state of exhaustion. Apparently, immune cells in this state start shooting a lot of blanks: they’re firing but not hitting their targets. This could explain the “hyperinflammatory” immune response seen to the coronavirus in ME/CFS, as well as the difficulty ME/CFS patients may have in reining in an EBV infection.
Herpesviruses
Representation of the EBNA1 protein. High levels of antibodies to EBNA1 have shown up in both multiple sclerosis and ME/CFS. (Image by Jawahar_Swaminathan_MSD_staff_European_Bioinformatics_Institute_Wikimedia-Commons)
While the coronavirus infections were “mild”, they were nevertheless able to reactivate EBV, HHV6 and HERV-K in both the people with ME/CFS and healthy controls. As noted above, EBV has been the source of much interest in ME/CFS, and EBV reactivation has been found, but no consensus exists as to whether EBV reactivation is driving the disease, contributing to it in some fashion, or is just a bystander.
The authors pointed out that the same issues have been dogging multiple sclerosis and other diseases for decades. Because virtually everyone gets infected with EBV at some point, it’s been difficult to study. Not everyone, though, gets infected.
The Gist
- A clever Swedish study compared what happened when people with chronic fatigue syndrome (ME/CFS) or healthy controls were infected with the coronavirus.
- They zeroed in on antibodies – the immune factors produced by B-cells that play an important role in the adaptive immune response that takes several days to kick in but which is largely responsible for eradicating pathogens. They focused on antibodies to the coronavirus and to herpesviruses and their possible reactivation.
- The first rather startling finding indicated that a surprisingly high percentage of people (42% ME/CFS; 31% healthy controls) had been infected with the coronavirus without knowing it! That means that some people with ME/CFS who thought they did not have a post-infectious onset may very well have.
- Ironically, the immune-challenged people with ME/CFS appeared to more rapidly pounce on the coronavirus than the healthy controls. Even more ironically, this “hyper-inflammatory” response is associated with immune cells that are in a state of “senescence” or in their dotage. Apparently, cells in this state fire off a lot of blanks that miss their targets.
- Another intriguing finding came when the researchers found that the asymptomatic controls had antibodies to the coronavirus in their saliva but not in their plasma. That indicated that they had been able to knock out the coronavirus before it got in their blood.
- The coronavirus was able to reactive herpesviruses and the HERV-K endogenous retrovirus in both the ME/CFS patients and the healthy controls.
- Epstein-Barr virus – a herpesvirus – has been the subject of a good deal of study in ME/CFS – and while no consensus exists about its effects, many people came down with ME/CFS after infectious mononucleosis/glandular fever – which is typically caused by EBV. Some studies suggest it could play a major role in some people’s illness. The same confusing scenario has existed in multiple sclerosis (MS) for many years.
- EBV is hard to study because it’s almost ubiquitous. A recent Harvard Dept. of Defense study found, however, that virtually no one who’s never been infected with EBV comes down with MS and that people who have been infected with EBV are about 30x’s more likely to come down with MS. EBV is now thought by many to probably be the main driver of MS.
- That’s an intriguing finding given the same EBV protein (EBNA1) that’s been implicated in MS popped out in the ME/CFS patients in this Swedish study. Levels of antibodies were EBNA1 were much higher in the ME/CFS patients after they’d been infected with the coronavirus than the healthy controls – suggesting that EBNA1 was more active in ME/CFS. That, of course, suggests that a particular susceptibility to EBV might be present in ME/CFS. Indeed, prior to the coronavirus infection people with ME/CFS were also more likely to experience EBV reactivation than the healthy controls.
- EBNA1 is a pretty potent protein. It’s the only protein being produced during EBV’s latency stage, has been implicated in EBV-associated cancers, and is able to stop T-cells from killing EBV-infected cells.
- People with ME/CFS were also more likely to experience reactivation of the HERV-K endogenous retrovirus.
- Time will tell what will happen with EBV and ME/CFS but the coronavirus, the multiple sclerosis finding, long COVID, and research like this have put an increased emphasis on EBV.
- One idea is to develop a “therapeutic vaccine” that could boost the immune response to EBV in people who already are infected with it. Antiviral therapies and therapies that target B-cells that harbor EBV are other options.
- The recent discovery of new antibodies the body produces to fight off EBV may help produce more effective drugs. New monoclonal antibodies were able to recently effectively block EBV from infecting cells in the lab. Some drugs can also block some of the transcription factors EBV has inserted into B-cells.
- A lot of work on EBV appears to be going on – and that’s potentially good news for ME/CFS and long COVID.
The MS saga may be illuminating in more ways than one. A recent Nature study tagged an EBV transcription factor called EBV nuclear antigen 1 (EBNA1) as a possible culprit in MS. Transcription factors turn on and off a wide array of genes. in MS EBNA1 appears to be mimicking a human protein called glial cell adhesion molecule (GlialCAM) that the body is attacking in MS – producing an autoimmune reaction.
The EBV autoimmunity connection got a big boost when a 2018 study found that EBV was transmitting a different transcription (EBNA2) into the genome of cells that appeared to be turning on genes associated with autoimmunity in a wide variety of autoimmune diseases.
Rather remarkably, it was EBNA1 IgG antibodies that popped out in the ME/CFS patients in the Swedish study – suggesting that EBNA1 is more active than usual in ME/CFS. That. of course, suggests that a particular susceptibility to EBV reactivation might be present in ME/CFS. We don’t know what EBNA1 is doing in ME/CFS but we do know it’s a powerful protein that plays a crucial role in EBV’s success and its ability to hang around in cells.
EBNA1 is the only viral protein that gets expressed when the virus is in its latent state. It’s also the only viral protein that researchers have found expressed in all EBV-associated cancers. Plus it’s able to shut down the attempts of T-cells to destroy EBV-infected cells. Now the question becomes what EBNA1 may be doing in ME/CFS.
A further twist in the EBV/ME/CFS story came when people with ME/CFS who had not been infected with the coronavirus were still found to have evidence of EBV reactivation (higher EBV VCA antibodies).
Antibody responses to the HERV-K endogenous retrovirus were also increased in the ME/CFS patients whether they’ve been infected with the coronavirus or not. HERV-Ks have shown up from time to time in ME/CFS, and one researcher even received a major NIH grant to assess them in ME/CFS. That project apparently didn’t turn out, but a recent hypothesis proposed that EBV, HERV-W/-K, and HHV-6 are driving the inflammatory cascade found in multiple sclerosis.
The Upshot
The upshot of all this is that people with ME/CFS responded differently immunologically in a most curious way to the coronavirus than did the healthy controls. For one, they exhibited high levels of antibodies to an Epstein-Barr virus-produced transcription factor that’s been implicated in multiple sclerosis (MS). For another, evidence of EBV reactivation was present prior to being infected with the coronavirus. Antibodies to the HERV-K endogenous retrovirus were also increased. Lastly, the authors noted that it was crucial to test for EBV antibodies in the saliva – not the blood.
The infectious mononucleosis/glandular fever connection in ME/CFS, the solidifying autoimmunity/EBV connection, the strong possibility that EBV infections are driving MS, the upregulation of the EBNA1 antibody in MS and ME/CFS connection, the emergence of EBV in long COVID, would seem to put EBV ever more in the crosshairs.
The Future
The authors reported that their studies into ME/CFS and EBV will continue. Eirini Apostolou, principal research engineer and lead author of the study, told Medical Express:
“We now want to continue and carry out more detailed investigations into the immune response in ME/CFS, and in this way understand the differences between the antibody responses against latent viruses,”
Of course, time will tell what will happen with EBV, ME/CFS, and long COVID. It should be noted that other studies have not found the EBNA1 elevation that this one did. What to do, though, if EBV reactivation turns out, in the end, to be a critical factor in ME/CFS and long COVID? Interest in EBV therapeutics appears to have increased dramatically recently with the findings in MS and long COVID.
One idea floating around the MS world is to develop a “therapeutic vaccine” for people who already have MS that could boost the immune response to EBV. Antiviral therapies and therapies that target B-cells that harbor EBV are other options.
Rituximab – an autoimmune drug – of course, failed in ME/CFS, but some think the trial was hampered by a lack of funding, and better autoimmune drugs are now present. The recent discovery of new antibodies the body produces to fight off EBV may help produce more effective drugs. New monoclonal antibodies were able to recently effectively block EBV from infecting cells in the lab. Some drugs can also block some of the transcription factors EBV has inserted into B-cells.
Spirolactonone presents an interesting possibility as its an old drug that could be repurposed to treat EBV.
One option, interestingly, maybe anti-retroviral drugs, as it appears that HIV drugs may reduce risk of getting MS. A recent paper on infectious mononucleosis stated, “There is great interest in developing antiviral regimens for treating infectious mononucleosis.” and noted how poor the current regimes are. One study estimated that it would take at least 11 years of valacyclovir treatment to clear an EBV infection.
In any case, a lot of work on EBV appears to be going on – and that’s potentially good news for ME/CFS and long COVID.
Thank you, Cort!
I guess reactivation of endogenous viruses needs to be taken seriously for a simple reason: what has been described for ME/CFS is pretty much the same what has been described as consequence of viral reactivation (mostly human heresviruses like EBV:
1) changes in mitochondrial function
2) Changes in peroxisomal function
3) Changes in metabolic functions (incl. mevalonate, glutame and tryp/kyn pathways)
4) Changes in endothelial function
5) Changes in immunologic functions, including inflammation and autoimmunity
6) Neuroinflammation
ME/CFS may indeed be a HHV-reactivation syndrome, and, possibly, severity may relate to the degree of reactivation?
That’s quite a list! 🙂
Hello Cort, thanks for another excellent piece.
There’s been a lot of focus on long covid research of late, but I think the ME/CFS community would also do well to keep a close eye on MS research.
I’d like to tease out a couple of things about EBV and MS; everyone one with MS has had EBV, but no one who hasn’t had EBV gets MS. In other words, EBV is a necessary condition for MS even if it isn’t a sufficient one on it’s own. Second, if someone has had mono/glandular fever the risk of MS goes up six-fold. There is no reason EBV can’t generate a range of auto-antibodies via cellular mimicry, which give rise to MS (proven), Lupus (very likely and ……..ME/CFS. EBV is still the single most common cause of ME/CFS which follows in about 5 to 10% of cases. All sound familiar?
I’m going to stick my neck out and say that a great many of us are suffering from ‘long mono’.
And of course, no reason why other viruses that persist in the body after the main infection can’t work in a similar way.
“long mono” – I like it! First time I’ve heard it framed that way. Very nice. I wouldn’t be surprised at all 🙂
Great response.
I have suspended this for a long time.
I have recovered mostly at least to be engaged in the world again after 20 years of ME.
I tried just about everything but I think many years of consistent Acupuncture and Chinese herbs did the heavy lifting with my immune system, gut and energy. I pace myself but have a life now!
Thanks – feel free to make it your own if you see fit! No royalties!
I am very curious about whatever Bhupesh Prusty will publish next. I am sure you’ve seen his tweet about having discovered lab evidence of a Herpes-virus related mechanism that makes sense for ME/CFS, but will take more time to properly research https://twitter.com/BhupeshPrusty/status/1591062181675761664?cxt=HHwWgIC8pfuny5QsAAAA .
Yes, indeed. I am behind with Bhupesh. Thanks for the reminder.
When I saw Dr. Cheney in 1986-1987 he talked a lot about EBV and no matter how many think CFS/ME IS NOT CAUSED BY EBV, it keeps coming back up. No one knows how to get rid of EBV OR any of that awful herpes family. If EBV can cause lymphoma it certainly, in my humble opinion, can create a lingering inflammatory state. CFS has been such an uncomfortable debilitating journey that has ruined many lives and relationships. At least more people believe it’s real but that doesn’t make me feel better. I have had to battle family members who were and are doctors over this which always left me angry. You all know, it’s been HELL. love to Cort for doing this blog. He’s a great help. Be sure to donate to him so he can continue. Recurrent monthly donation is the best for him. LOVE TO ALL OF US. hipjaven
Thanks again, Javen – sorry to hear about all the battles! Hopefully, even they will come around over the next couple of years. Thanks for the support as well – Donation drive starts tomorrow (!)
thank you Cort for giving hope!
what a nice twist for ME/cfs these researchers made with long covid!
may i ask (i can now not read well and do not know so much):
– how long would it take untill there are for everyboddy tests and treatments?
– i read somewhere that with product x it would take 11 years to get rid of ebv, would precisionlife (https://precisionlife.com/medrxiv-genetic-risk-factors-for-me/cfs-identified-using-combinatorial-analysis) for excample be able to fast track meds that would clear the job easier? what they all have in the pipeline for diseases but i put it on ME/cfs
–
Is the “overreaction”, could it be a reason that so many ME/cfs patients react so bad to the covid vaccins?
hope i do not ask to stupid questions but really severelly ill..
Konijn, these are excellent questions. Hope we get a lot of good information based on these questions.
Is the “overreaction”, could it be a reason that so many ME/cfs patients react so bad to the covid vaccines?
That’s a nice idea! I wonder….
I just found out about Precisionlife. The more precise the better for sure. If you identify who the EBV reactivators are and how their genes are responding – all the better 🙂
I really don’t know. If its a new drug it can take years of course. If they can repurpose an old drug like spirolactonone – much quicker!
https://www.healthrising.org/blog/2020/07/22/epstein-barr-virus-spironolactone/
It was reacting “so badly” to a Covid vaccine in January 2021 (AstraZeneca knocked me out for three days, as a really bad FM flareup plus pounding headache & total exhaustion) that first strongly suggested to me that CFS/FM must be an autoimmune, post-viral condition.
As it also made sense, as a Herx reaction, of an FM flareup I had had in 2015 in response to over-enthusiastically embarking on “grounding” (getting free electrons from the Earth, which as a species we evolved in contact with mainly via bare feet). But evidently I’d started grounding too fast for too long — provoking a rapid and toxic pathogen die-off. (EBV?)
But my FM flareup provoked by grounding was misdiagnosed at the time (by someone less expert than she thought) as due to EMFs around my bed, until I bought EMF and volt meters and measured them: both negligible. Been given the wrong explanation.
(And so a year ago I started grounding again — this time starting with an hour a day, gradually increased. No problem this time: just better sleep, more energy, less exhaustion.)
And the autoimmune theory of CFS/FM was then clinched for me by reading the Karolinska Institute’s 2021 study six months after my AstraZeneca vaccine reaction, about the effects of injecting IgG antibodies into mice from blood serum of a group of people diagnosed with FM.
It fitted perfectly. And since then, more and more studies are implicating EBV reactivation in ME/CFS/FM.
thank you!!! i am so bedridden, 98%, i could not stand on the ground for an hour. sorry, i speak normally dutsh. is grounding standing with naked feet on for excample gras in the garden? i will try if i can 1 minite but if i can not do it, can you grounding with sitting to? and what if it is freezing? it is hee now icecold. i had 2 pfizers and booster moderna. now i rejected. but have they also IgG? i thought not because of being Mrna?but i am verry ill so not shure. or was astra zeneca also an Mrna vaccin? do you have maybe links to phizer and moderna? or can tell me the difference between your astra zeneca and pfizer and moderna. And how, if possible to get over it? so glad you are better!!! did it take long?
In reply to “Anonymous” (sorry, there was no Reply button under your comment) I will try to answer your questions.
“i am so bedridden, 98%, i could not stand on the ground for an hour… is grounding standing with naked feet on for excample gras in the garden?”
Sorry you are so ill. I too have difficulty standing for more than a few minutes, too exhausting. (Though walking is not so bad, unless it’s uphill — also exhausting.)
Yes “grounding” can be done with bare feet on wet grass — best of all in the sea (salt makes sewater highly conductive) but this is not practical in high latitudes in winter.
So have a look at http://groundology.co.uk for a range of earthing/grounding products you can use indoors, in bed, connected to the “Earth” pin of 3-pin electrical power sockets — after testing they are correctly wired and safe.
I now use a couple of earthing wristbands on each wrist, but started off (in 2015 — quickly abandoned due to the unexpected reaction) using earthing sheets (woven with conductive silver strands) plus earthing socks.
An earthing mat is multipurpose and cheapest if other options are too expensive: eg can be used under a laptop or tablet computer (as the worst source of EMFs), then slept on in bed.
“I had 2 pfizers and booster moderna. now i rejected. but have they also IgG? i thought not because of being Mrna?but i am verry ill so not shure. or was astra zeneca also an Mrna vaccin? do you have maybe links to phizer and moderna? or can tell me the difference between your astra zeneca and pfizer and moderna. And how, if possible to get over it? so glad you are better!!! did it take long?”
Pfizer / BioNTech and Moderna Spikevaccine are both MRNA vaccines, and are entirely lab-engineered.
But AstraZeneca vaccine is based on the adenovirus (which causes a common cold in chimpanzees) with only its spike proteins engineered, to closely resemble the SARS CoV-2 coronavirus spike proteins.
But both kinds of vaccine work in the same way: using the engineered spike proteins to provoke our immune system into a response which “trains” it (the adaptive part of it) to cope more effectively, if our immune system then encounters the real thing.
(I’ve had two AZ shots, with no reaction to the second shot; then Pfizer with a short fairly mild reaction; then Moderna with a longer nastier reaction — still nothing like as violent as the first AZ shot; then a Moderna bivalent, including adaptation for Covid Omicron strain. Reaction mostly a sore arm.)
IgG antibodies are Immunoglobulin G, specific (so far as I know) to the agent provoking an immune reaction. So IgG would be produced by our own immune systems in response to the coronavirus or to a vaccine: IgG would not be in the vaccine itself.
I’m pretty sure that grounding/earthing helped me to recover from Covid vaccinations, as part of the difference it’s made generally: though I couldn’t say I’m completely recovered. It’s certainly helped with neuropathy: I longer feel the firy, burning sensations — used to be like a bath of fire.
But I suspect I’m now dealing with much older musculosketal problems, originating in extreme & lifelong muscular tension from CPTSD (I am now 80) and spinal osteoarthritis since 1976. Changing my diet to Vegan in 1976, and later Alexander Technique, both helped enormously with this. And I’m currently looking for an Alexander teacher again.
I hope this is helpful to you. Please, if you try grounding, start catiously — with just an hour a day, increased by an hour each day until you can sleep grounded. I hope it helps you as much as it helped me.
And try signing up to “Earthing Insiders” on Facebook where you can share experience, ask questions and get answers from other users and from expert researchers.
Well it’s about bloody time!
My M.E./C F.S. was 100% caused by EBV. In the last five years my EBV has reactivated five times (including now, as I write this). I wish more research was studying this – looking at YOU Open Medicine Foundation and Griffith University in Australia. I’ve already lost nearly 30 years of my life to this disease. Get on to it !!!!!
Hi Wayne, in my country, if infection, they never look of what kind of infection. and also ill since ’94, they did not look then, they certainly look now not anymore. here it is get and cbt… Did they just do a blooddraw specially for ebv? or with saliva? thanks a lot!! so sorry you are also allready so long so ill!!! hope they can help you soon!!!
Yes the initial EBV and subsequent EBV reactivations have been detected in blood tests.
You know, Wayne, it’s the chicken and egg thing. EBV gets reactivated BUT the real deal is what’s making it reactivate? I’ve lost 36 years. What a shame for so many of us. The few people I have left just don’t want to hear me say one more time “I DONT FEEL GOOD”. Hipjaven
That’s simple. Having low CD8 immune cells is what makes EBV reactivate so easily.
Say it like it is, Wayne! I think we can rest assured that EBV is going to get a lot more ink in the next couple of years.
I’ve had my ME associated with reactivation of EBV 2-3 times/year for 20 years. Since early 2020 when Covid showed up, my EBV has remained activated continuously.
ME also seems to be associated with increase in both physical and mental stress, which may be where the association with Glutamate, etc may come into play.
Sorry to hear your EBV reactivates so frequently. That’s horrible. I know a reactivation has occurred when I need to fall asleep during the daytime. Usually (with M.E. I feel fatigued), but with EBV it makes me need to sleep. Is that the same with you? I didn’t get reactivation issues until I got to 50 years old. Apparently as we age, our immune system finds it more difficult to fight the virus.
Interestingly I have never had EBV (no serological evidence of any historical infection), but do have severe ME with POTS.
It’s possible that I’m an anomaly, but I’m inclined to think that EBV is simply one of many possible triggers, and in the disease process it may be an aggravating factor but likely not the perpetuating factor.
Yes exactly. I came down with CFS several years before I got EBV for the first time.
As I l have said many times, a number of viruses can trigger (but do not perpetuate) CFS. But other things can too.
Have you been tested specifically for EBV?
Yup, specifically tested for EBV, VCA IgG, VCA IgM, EBNA IgG, all tested negative.
Looking to be in touch with others who have chronic fatigue to share and COMISERATE with other to support each other…..(hope i spelled it right)
As far as I know, EBV can not be the cause of ME as the incubation time for EBV is something like 40 days I think whereas the incubation time for ME epidemics is 4-7 days if I remember right. I read this in Dr Hyde’s book. I also know that Lake Tahoe was an ME epidemic not caused by EBV as originally thought as half the patients had no EBV titres/or no EBV reactivation/no EBV.
@Martin
We need to differnetiate between EBV as the “cause” of ME/CFS (i.e. the trigger causing the inception of ME/CFS) and EBV reactivation as the factor that sustains ME/CFS (no matter what virus/microbe triggered the inception).
I don’t think EBV causes ME/CFS and I never ever had an EBV reactivation yet I was still ill with ME/CFS. If EBV were the cause of ME/CFS. we would all know by now as it is simple to test for. Half of the Lake Tahoe as I mentioned never even had EBV reactivation yet they were ill.
Good point. Many of us contract EBV when we are children and it goes unnoticed. Those who contract it later as adolescents and adults have a much harder time fighting it off but those who contract it earlier and can fight it off still harbor it in their tissues. This and other studies indicate that an infection can trigger its reactivation.
We do need to know and I suspect we will know at some point if the tendency for reactivation is in any way dependent at which stage of life the original infection occurred.
@martin
No, EBV reactivation is not that easy to diagnose as many cases are missed if only blood is being tested (see the study summarized by Cort: in many cases you could detect EBNA1 IgG in the saliva, but not in blood). Also, reactivation of microbes does not only extend to EBV but may consist of the reactivation of other species of HHV or other viruses/microbes. EBV ist just an awefully commonly reactivated species.
I like differentiation 🙂 Is there also a third possiblity that ME/CFS sustains EBV reactivation (i.e. EBV reactivation as consequence not cause)? Or do you think that less likely based on you overview of literature?
@JR
Yes, certainly! ME/CFS can sustain reactivation of endogenous viruses in a vicious circle way. For example, high adrenergic output (part of dysautonomia in ME/CFS) can cause pretty deep-level immune dysfunction which may explain why the reactivation never stops. Also the tissue hypoxia/oxidative stress associated with ME/CFS can sustain reactivation. The same is being discussed for metabolic/mitochondrial problems: poor availibilty of energy and/or toxic by.products will first hit the delicate immune cells and make them less functional – and again this may not really help to competently deal with reactivated microbes in the body. Also of possible interest that endogenous viruses like herpesviruses replicate predominantly in B-cells and in endothelial cells – possibly with direct effects on their functionality.
My son’s EBV came on after the fatigue and orthostatic intolerance were established. Like Lake Tahoe ME sufferers, his fatigue was caused by mould after our roof cavity and insulation was contaminated after multiple cracked tiles caused roof leaks. I see a lot of connections both in Cort’s article about the study and in the comments.
The approach that worked for him was to bind the mould in his body using cholestyramine then increase mitochondrial health with D-ribose, carnitine, fish oil, turmeric, quercetin, antihistamines, B1, l-theanine, ashwagandha, melatonin and magnesium. He recovered on this protocol combined with the Covid vaccinations and methylphenidate.
In fact, the vaccinations seemed to be the thing that finally got him well. He’s been free of fatigue for 1 year now, after being unwell for 2+ years, 18months housebound. Fingers crossed that he makes it past the 5 year mark now.
would you please want to write the doses and when and how to take of what your son took? was he ever bedridden if i may ask? I really hope for you and him that he stays well!!!
All doses were standard according to either Dr Myhill and/or Dr Tenebaum and the B 1 dose was Benfotiamine 800mg. Both Doctors websites and books are available. We tended to follow Dr T in the end because it had multiple options. He wasn’t bed bound but didn’t move much from his spot on the couch
If EBV triggers mecfs neuroinflamaton and EBV reactivation is unique to mecfs patients, then COVID infection should leave mecfs patients particularly worse off. That should be fairly easy to verify.
Anecdotally, I contracted COVID on the road in September and I still climbed Colorado’s fourteeners 16 days after the initial infection. It was a little scary though when fatigue, weakness and blurriness continued for another week after the major symptoms were gone on the day 7. It felt just like PEM.
If reactivation of endogenous microbes is a central feature of ME/CFS (no matter if sustained by EBV, HHV6, enteroviruses, HERV-K, toxoplasma, borrelia…) the question would be: what to do about it?
Here we may want to consider a couple of facts:
– endogenous microbes (incl. EBV) are part of the human evolved biology
– they are usually kept latent (i.e.. under control, dormant) by the innate immune system
– intermittent flare-ups of endogenous microbes are to be observed in healthy people when the immune system is heavily engaged. A competent immune system will then kick in and bring the microbes back under control
– it is accepted among virologists that the antivirals currently on the market (which have been developed to fight viral infections) are *not* able to stop viral reactivation in the long run
– the competence of the innate immune system is an evolved system which relies on constant “training” by environmental input stimulating the innate immune system – like beta-glucans and certain ubiquitous environmental bacteria like mycobacteria (“old friends” hypothesis – see: https://pubmed.ncbi.nlm.nih.gov/20415854/)
– there is evidence that the reduced immune stimulation from the living environment can shift the immune balance towards autoimmunity and that this may be behind the surge of autoimmune disorders in the last 50 years ((https://pubmed.ncbi.nlm.nih.gov/15007629/))
It is therefore a plausible idea to mimic the input of our “old friends” to strengthen the innate immune system in its competence to control the endogenous human microbiome.
This is being pursued by what is called “trained immunity” interventions ((https://www.nature.com/articles/s41577-020-0285-6 // https://onlinelibrary.wiley.com/doi/full/10.1002/mco2.121)).
Here, the strongest effect may be to mimic the effects of mycobacteria (which have engaged the human immune system since the times of the Neanderthals). This can be done by applying BCG vaccinations (BCG is a cultured, attenuated Tb-bacterium): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896902/ // https://www.frontiersin.org/articles/10.3389/fimmu.2018.02936/full // https://www.pnas.org/content/118/21/e2101718118
This apporach has been tried in two autoimmune conditions:
a) In humans with early onset Type 1 Diabetes (T1D) 3 repeated BCG vaccinations (two back-toback vaccinations 4 weeks apart, then another one year later) have been shown to induce long-term clinical remission. Blood glucose was restored to near normal, even in patients with advanced disease of >20 years duration. Of note: this was a double blind randomized controlled trial (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873620/)
b) In Multiple Sclerosis (MS) – a disease now understood to be pathobiologically related to a maladapted response to an infection with EBV – a single dose of BCG vaccine was shown to prevent progression to clinically definite disease when given after a first demyelinating event. Follow-up during the trial showed that the clinical effect of BCG was even more pronounced at 5 years after vaccination. Again, these results were obtained in an RCT ((https://pubmed.ncbi.nlm.nih.gov/22905105/))
Interestingly, BCG vaccination has been shown to mitigate the reactivation of endogenous viral infections, e.g., Epstein Barr virus (EBV) ((https://pubmed.ncbi.nlm.nih.gov/31055165/)) – which made the authors state: “„BCG administration might be considered as treatment to prevent reactivation of latent v iruses, such as varicella zoster virus (VZV), cytomegalovirus (CMV) or Epstein–Barr virus (EBV)“.
Based on all these considerations I do think that BCG vaccination should also be explored for ME/CFS.
Here is a short write-up on this suggestion:
https://www.kinder-verstehen.de/wp-content/uploads/BCG_hypothesis_short_251222.pdf
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Danke for explaining BCG approach
That was what the folks who created the FMA test for Fibromyalgia had in mind. Collect test data and trial the BCG vaccine for Fibromyalgia. A while back Mayo was trying to validate their test, but all I heard in the end was that they couldn’t get funding for the trial. Also, Covid came along and they got involved in some aspect of their test data showing FMS patients having some protection from Covid. A lot of people were excited that they might be part of the BCG trial. I tested in the 90’s, which according to them was a definite positive for FMS. I will say the insurers and Medicare ended up paying for the test. If nothing else it was a cheaper way out than all the doctor’s visits to try to diagnose FMS. One blood test and that was it. I was very disappointed about the whole thing as were many others. Cort may know more about it as it was being followed here on HR.
@Cynthia
Unfortunately, this test may have been based on predatory advertising: https://www.statnews.com/2021/10/20/selling-certainty-epicgenetics-physician-was-one-of-fibromyalgia-patients-few-true-allies-or-was-he/
We are still far from an accurate “test” for fibromyalgia (ans ME/CFS, of course
Dear Herbert, thank you for solving this mystery. How disappointing the story of the FMA test and BCG trial turned out to be. And Gillis walks away without penalty. I had a little hope when I saw the Mayo press release info on the Epicgenetics site. And I remember thinking how are they going to enroll these tens of thousands of test recipients in a clinical trial? Still there is a part of me that wonders what is in those results? But a ME CFS and FMS doctor I highly respect never believed it was a real test. Why is this all so hard to figure out? I keep thinking it is all wired into our genes somehow and we can’t undo that. Such a complex reaction or mechanism in our bodies.
Restore the metabolic rate
EBV is still a mystery.
Also nice to see that unvaccinated ME patiënts did respond well on covid. I know some ME patients too who did respond well on covid.
Did you already have had covid Cort?
Everybody will get it sooner or later. I have had it and did fine too. I have had mild to moderate symptoms. Within a week i was normal again.
Thank you for reviewing this research and connecting it to other studies. Makes me understand it better!
Thanks for the article & all the insightful comments. For folks who are having EBV reactivations, have you found tools and meds that help you bounce back sooner?
I had CFS after mold exposure and eventually (8 years later) was diagnosed using antibody tests with EBV and CPn. Before finding a Dr. who could diagnose and treat my CFS, I researched symptoms and took supplements. Some symptoms overlapped those of MS.
Notably, MS patients never have gout. Uric acid in excess causes gout but is also part of the purine metabolic cycle. Purine is needed for B and T cell function. B cells and Purine/ uric acid are depleted in chronic infection and immune function is impaired.
I took Inosine to boost uric acid. Adding DMAE and Ornithine/ Arginine recreated Imunovir with off the shelf supplements, an antiviral used for CFS.
Did it work? Hope so!! What is CPn please?
I’ve been over CFS but have lingering damage from chronic infection. Covid has triggered other symptoms. My recovery story is on this site:
https://www.healthrising.org/forums/resources/thirteen-years-after-occupational-exposure-doug-is-well.77/
I don’t believe that my Covid triggered EBV, which i know i’ve had activated about 3 times in my life. I
So I believe that i MUST have some of the OTHER Herpes Viruses like HHV6, etc., that got activated during/after Covid, that were never tested Because I’m still run down after getting covid 3 months ago.
I hope someday that the research will show how to stop the virus activations with natural supplements, not drugs that cause “side/direct effects”.
And how do we turn down the Cytokine Storm? What natural supplements can do this?
Try grounding, which you can read about here: groundology.co.uk (includes links to research, a video & book).
Research has shown that getting free mobile electrons from the Earth prevents the inflammation cascade — thought to be because free electrons are stored in the fascia (a tough membrane that separates internal organs, made of collagen which is a semi-conductor) which delivers them promptly to any site of injury or infection.
Grounding works very well for me in improved sleep, increased energy and reduced exhaustion — though this is only relatively speaking, as I’m still fairly incapacitated by CFS/FM (for 20 years).
A warning: if you try grounding, start slowly, at eg an hour a day, increased by an hour a day until you can sleep grounded. Otherwise you risk a “Herxheimer” reaction, of provoking too-rapid die-off of pathogens (eg EBV) which is toxic to the system, & will likely manifest as a CFS/FM flareup.
PS (sorry) http://www.groundology.co.uk
If anyone is interested in learning more about EBV, I highly recommend reading Anthony William’s book on Chronic Mystery Illness. Anthony has been talking about EBV for years. I’ve learned more about EBV from his book/s than any other source. According to Anthony, there are now approx. 60 different strains of EBV and that is why everyone will have various symptoms. It depends on the strain or strains of EBV one is carrying. Also, concerning long haul covid, Anthony has been saying underlying viruses such as EBV are being triggered to act up and that is why people have symptoms that continue. It is not the corona virus anymore causing symptoms but the underlying herpetic virus or viruses. He said this long before any articles/studies started making the connection.
EBV also = Alzheimers / Lupus flares / MS / Dementia / ME-CFS. Pollutants have damaged the immune system / DNA.