To those who believe their ME/CFS began w/ EBV.....

[sometexan84]

I want to preface this with the following...

1. I understand and agree that the cause of ME/CFS is yet to be proven
2. I am very much not trying to offend anyone
3. I understand and respect our group's diverse set of opinions
4. Many of my opinions here, I'm aware, are not fact, even if my wording suggests fact, that's not really intentional
5. I don't want people to get mislead, go down the wrong path, that's all

I know many people strongly believe their ME/CFS began from an EBV infection. And I think this could actually be the case in some, especially if it was from acute infection and not a re-activated EBV infection.

In my first 10 months or so of research, I was completely sold on the idea that if I followed the late Dr. Martin Lerner's protocol, got rid of EBV, then I'd be cured. And I regrettably wasted so much time on this theory.

Whether or not you're sold on the Enterovirus B theory, the fact is, these infections can and will re-activate EBV.

If your story is anything like mine, you'll be tested for EBV way before even learning about Enterovirus B and its relationship to chronic fatigue symptoms.

And as such, it's very natural to point to these abnormal EBV results as the cause, especially when you hear EBV is connected to ME/CFS.

From the Enterovirus Foundation....

Enterovirus infections can trigger dormant viruses to reactivate, such as HHV6, Epstein Barr Virus, CMV, and chickenpox– all herpes viruses.

you can find a lot of research out there backing this up.

More recently, an article on Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

Where 67% Long Covid patients had reactivated EBV versus 10% controls.

And I don't think anyone can deny that it was SARS-CoV-2 that started their LC/ME/CFS, and not EBV.

And the RNA viruses SARS-CoV-2 and Enterovirus B are so insanely similar it's crazy. I'm telling you, EBV is probably not the cause of your ME/CFS.

But alas, there was no global Enterovirus B pandemic to point to in ME/CFS. So, we're left with everyone going "What do you think?"

Well, this is some of what I think. Hopefully it's helpful to some.

 

[Hip]

If your story is anything like mine, you'll be tested for EBV way before even learning about Enterovirus B and its relationship to chronic fatigue symptoms.

Indeed, the ME/CFS specialists who focus on herpesviruses (like EBV, cytomegalovirus and HHV-6 are) more numerous than specialists who focus on enteroviruses (like coxsackievirus B and echovirus).

So many ME/CFS patients will have active enterovirus infections, but not know about it, because their doctor did not bother to test for enterovirus (or used insensitive tests which cannot detect chronic enterovirus — the sensitive tests are the antibody tests which use the neutralization method, rather than the ELISA, IFA or CFT methods).

 

[junkcrap50]

In my first 10 months or so of research, I was completely sold on the idea that if I followed the late Dr. Martin Lerner's protocol, got rid of EBV, then I'd be cured. And I regrettably wasted so much time on this theory.

Did you dose it correcly? HOw did you get enough valacyclovir? For me, I would have to take 2x1000mg 3xday. Insurance will only pay for 1 or 2 per day, well below the recommended amount. 2000mg is for larger adults.

But alas, there was no global Enterovirus B pandemic to point to in ME/CFS. So, we're left with everyone going "What do you think?"

There have been wide Enterovius C pandemics (poliovirus) causing ME/CFS, which they called Post Polio Syndrome.

 

[sometexan84]

Did you dose it correcly? HOw did you get enough valacyclovir? For me, I would have to take 2x1000mg 3xday. Insurance will only pay for 1 or 2 per day, well below the recommended amount. 2000mg is for larger adults.

2000mg 3x/day? So 6,000mg/day!?!?

Julius Caesar that is a lot!

I was doing 500mg 4x/day. A little below that protocol. That is still a lot of valacyclovir. Did for long time.

There have been wide Enterovius C pandemics (poliovirus) causing ME/CFS, which they called Post Polio Syndrome.

Yea, I probably should have highlighted or bolded the "global" part. Like, there's been no global pandemic, nothing compared to covid obviously.

 

[nerd]

I think we have to differentiate etiology from pathogenesis here. If a virus triggers EBV reactivation, and there are many more than just SARS-CoVs, entero- and herpesviridae that can actually do this, then the question is if it is the EBV pathology that plays its part in the pathogenesis of ME or if EBV pathology is just correlating noise.

When EBV remains subclinically active in a patient, and contributes to ME as a sleeping disease that just waits for a trigger to break out, I still see EBV as the causality.

There isn't a common denominator so far when it comes to viral matches, but the most commonly associated virus seems to be EBV so far. To be fair, EBV is more frequently tested than other viruses. It's possible that this is just a testing bias.

Moreover, it's possible that it is another endemic but not common enough virus variant that is also reactivated by similar mechanisms. There are many reactivation mechanisms but viruses are bound to the options of the intracellular metabolism and innate immune system. So overall, it's not that many that viruses can choose to integrate and coevolve.

This means that there's a good chance that it could be another virus as well, such as HHV-6. Or a family of viruses that share a certain viral gene.

The shared viral signaling that contributes to reactivations just isn't enough for me to believe in a specific virus as the main contributor.

I have more hope in identifying the main contributors to the pathogenesis by viral proteins and miRNA.

 

[Nuno]

When EBV remains subclinically active in a patient, and contributes to ME as a sleeping disease that just waits for a trigger to break out, I still see EBV as the causality.

Do we have any information on the EBV levels of the patients that Dr Chia treated?

If they reduced while on the treatment, and that would match with the reduce of the symptoms that would be interesting to know. Still, however, doesnt totally answer the question since many factors take play here

 

[nerd]

Do we have any information on the EBV levels of the patients that Dr Chia treated?

If they reduced while on the treatment, and that would match with the reduce of the symptoms that would be interesting to know. Still, however, doesnt totally answer the question since many factors take play here

I don't know. It's unlikely because there's not really an approved biomarker for this yet. If it remains in certain tissues such as the stomach, the brain or the CNS, they'd have to look for residues that spread from this tissue. As far as I know, the Charité and the University of Würzburg are currently working on identifying viral biomarkers for ME diagnosis.

 

[Hip]

There isn't a common denominator so far when it comes to viral matches, but the most commonly associated virus seems to be EBV so far. To be fair, EBV is more frequently tested than other viruses. It's possible that this is just a testing bias.

The only trouble with EBV and other herpesviruses like cytomegalovirus and HHV-6 is that they almost never cause viral epidemic outbreaks.

Not all viruses can cause epidemic outbreaks, only certain viruses can do this.

Cytomegalovirus and HHV-6 never cause epidemic outbreaks. They are not capable of this.

Very rarely, EBV may sometimes cause a small-scale outbreak among young people in say an institution like a hospital (but only young people like young nurses; older adults over around 25 will already have EBV, so are protected from re-infection).


Whereas enteroviruses frequently cause epidemics. They do this all the time.

You get epidemic outbreaks of polio (before vaccination became widespread), outbreaks of enterovirus 71, outbreaks of coxsackievirus B and echovirus. I tracked many enterovirus outbreaks in the last few decades on this page of my website.


So herpesviruses like EBV, CMV and HHV-6 will never be able to explain the historic outbreaks of ME/CFS, because they do not produce outbreaks. Whereas enteroviruses are strong candidates to explain these outbreaks, and were often suspected at the time of the outbreak, based on observations such as incubation period and symptoms of the patients.

Incidentally, the incubation period (time to onset of symptoms) can be useful for identifying viruses, if you know when you caught the virus. The incubation period of coxsackievirus B is 2 to 5 days, whereas the incubation period of EBV mononucleosis is 4 to 6 weeks — very different timescales.

The CDC investigation into the famous Lake Tahoe ME/CFS of 1984 was led up the wrong path by all the herpesvirus reactivations / high antibody levels that occurred in patients who caught the Lake Tahoe virus. But clearly the Lake Tahoe virus could not have been a herpesvirus, but could well have been an enterovirus.



That said, several studies have shown that ME/CFS can appear after an episode of infectious mononucleosis (glandular fever), see: here, here, here, here and here. Mononucleosis is caused by EBV 90% of the time, and more rarely caused by cytomegalovirus, and even more rarely by a few other viruses.

Acute EBV infection is not very likely to occur in people older than around 25 years old, as by around that age, 90% of people will have already caught it, so have protective antibodies against EBV.



In her recent review paper of enteroviruses in ME/CFS, Prof Maureen Hanson says:

Given that enteroviruses are known often to cause mild or asymptomatic infections, it is possible that individuals who report ME/CFS after mononucleosis or other herpesviral infections may have also had an inciting enterovirus infection before or after the herpesvirus infection.

In fact, one may speculate that an undetected enteroviral infection could make an individual more susceptible to symptomatic cases of EBV infection, for example.

Most individuals are infected with EBV as children, yet a number of patients have reported an adult-onset EBV infection as triggering their ME/CFS. Perhaps these adult cases are actually mis-diagnosed reactivated infections.

Indeed, there are several reports of reactivated herpesvirus infections in ME/CFS patients.

Furthermore, a few studies have discovered impaired immunological response to EBV in ME/CFS patients. Is this impaired response due to a prior or ongoing enteroviral infection?

 

[nerd]

The only trouble with EBV and other herpesviruses like cytomegalovirus and HHV-6 is that they almost never cause viral epidemic outbreaks.

That's not what I meant though. My point was that herpesviruses play a part in the pathogenesis, not necessarily the etiology. Just as with SARS-CoV-2. Many viruses can reactivate these herpes viruses. And it's possible that a strong reactivation is what is necessary to reach a certain threshold or reach a certain organ like the brain.

So it would come down to a complex picture of many contributors, mostly viral infections though, that trigger some other virus like EBV to reactivate. Genetic predisposition, metabolic stress, and an existing viral reservoir can then synergistically create the ME pathogenesis.

This theory is consistent with epidemic outbreaks and pandemics.

 

[Hip]

My point was that herpesviruses play a part in the pathogenesis, not necessarily the etiology.

Yes, that's certainly true. You may catch an enterovirus, and that causes some immune weakening, which then leads to reactivations or high antibody levels to some herpesviruses you already have in your body. Then it may be both the enterovirus and the herpesvirus which contribute to symptoms.

I am pretty certain my ME/CFS was triggered by coxsackievirus B4, based on symptoms, incubation period and my blood tests. But I also have high IgG antibody levels to cytomegalovirus (levels 34 times higher than the lab reference for negative). Hard to know how much each contributes to my symptoms.

 

[sometexan84]

I think we have to differentiate etiology from pathogenesis here.

That's very fair.

I certainly think it's possible EBV could be causing some or most ME/CFS symptoms (and I think "some" is more likely than "most").

But let's say for the sake of argument that EBV causes ALL symptoms. And say Enterovirus causes active EBV. You'd still want to treat Enterovirus in order to stop EBV.

There isn't a common denominator so far when it comes to viral matches, but the most commonly associated virus seems to be EBV so far. To be fair, EBV is more frequently tested than other viruses. It's possible that this is just a testing bias.

I am not so sure this is the case.

I did some comparisons a while back w/out bias, and found it's #1 Enterovirus, #2 EBV, #3 HHV6.

I just put everything I could find in an excel file like this...

and then totaled up the numbers like this...

Enterovirus

EBV

HHV6

 

[sometexan84]

So herpesviruses like EBV, CMV and HHV-6 will never be able to explain the historic outbreaks of ME/CFS, because they do not produce outbreaks. Whereas enteroviruses are strong candidates to explain these outbreaks, and were often suspected at the time of the outbreak, based on observations such as incubation period and symptoms of the patients.

Good point. I had never thought of that.

 

[Haley]

older adults over around 25 will already have EBV, so are protected from re-infection

I think I'm one of the minority - I was in my 30s when I got EBV.

 

[nerd]

But let's say for the sake of argument that EBV causes ALL symptoms. And say Enterovirus causes active EBV. You'd still want to treat Enterovirus in order to stop EBV.

Not as a CFS patient though. It would have to be treated during the infection. Later on, the enterovirus wouldn't play part in the pathogenesis, since it only triggered the reactivation. At least if we stick to this particular theory that only meant to serve my point that there are still other options.

So if you were healthy and knew that you had a risk for developing ME, this would be a reason to use antivirals as soon as viral infection symptoms occur. But most viral infections today aren't treated early. Not even COVID-19 is. I don't know what's going wrong with the virology community.

Regardless, once the trigger is set, antiviral therapies against the Enterovirus won't stop the herpes infection. Practically, there is a chance, of course.

I did some comparisons a while back w/out bias, and found it's #1 Enterovirus, #2 EBV, #3 HHV6.

I don't doubt the Enterovirus data as much as a doubt the herpes virus data. In most studies on herpes viruses, inappropriate biomarkers were used, from today's perspective, thereby making the end result very insensitive to the representation of real reactivation pathology. Historically, it's understandable. This is why we have to take older studies with a grain of salt.

 

[sometexan84]

In her recent review paper of enteroviruses in ME/CFS, Prof Maureen Hanson says:
"Most individuals are infected with EBV as children, yet a number of patients have reported an adult-onset EBV infection as triggering their ME/CFS. Perhaps these adult cases are actually mis-diagnosed reactivated infections. "

Yea, see that's another issue altogether. The misinterpretation of EBV results by docs and patients. Here's a screenshot from this thread showing the correct EBV lab interpretations...

 

[Hip]

Not as a CFS patient though. It would have to be treated during the infection. Later on, the enterovirus wouldn't play part in the pathogenesis, since it only triggered the reactivation.

Since enterovirus can form chronic low-level active infections (non-cytolytic infections), it's conceivable that it has an ongoing role in not only causing ME/CFS, but causing an immune weakness that allows other viruses to reactivate.

The data we have from interferon treatment of ME/CFS supports the idea that chronic enterovirus plays an ongoing role in creating ME/CFS symptoms. Enterovirus ME/CFS patients treated with interferon often show a dramatic improvement (herpesvirus ME/CFS patients do not improve on interferon).

Interferon is potently antiviral for coxsackievirus B. Unfortunately when you stop the interferon, the virus and the ME/CFS returns some time later, but the remissions can last for up to a year or so.

 

[sometexan84]

That's not what I meant though. My point was that herpesviruses play a part in the pathogenesis, not necessarily the etiology. Just as with SARS-CoV-2. Many viruses can reactivate these herpes viruses. And it's possible that a strong reactivation is what is necessary to reach a certain threshold or reach a certain organ like the brain.

So it would come down to a complex picture of many contributors, mostly viral infections though, that trigger some other virus like EBV to reactivate. Genetic predisposition, metabolic stress, and an existing viral reservoir can then synergistically create the ME pathogenesis.

This theory is consistent with epidemic outbreaks and pandemics.

This point is fair as well.

Even so, if Enterovirus causes a Th2 dominance and dysregulation of immune pathways and cytokine production, resulting in EBV reactivation from reduced Th1 (cellular immunity), and from reduced Immune surveillance.... well, then theoretically, it's still a matter of fixing the root cause, Enterovirus, allowing the body to recalibrate and immune system to get back on track.

 

[nerd]

herpesvirus ME/CFS patients do not improve on interferon

Interferon is used for the treatment of CAEBV though.

Since enterovirus can form chronic low-level active infections (non-cytolytic infections), it's conceivable that it has an ongoing role in not only causing ME/CFS, but causing an immune weakness that allows other viruses to reactivate.

It's certainly possible, I never disagreed with this. But only because there's a reactivation link, this isn't very conclusive in my eyes that it has to be an Enterovirus infection.

I only disagreed with the opinion that this would eliminate herpesviruses from the etiology or pathogenesis. In my eyes, this is still on the table.

Even so, if Enterovirus causes a Th2 dominance and dysregulation of immune pathways and cytokine production, resulting in EBV reactivation from reduced Th1 (cellular immunity), and from reduced Immune surveillance.... well, then theoretically, it's still a matter of fixing the root cause, Enterovirus, allowing the body to recalibrate and immune system to get back on track.

There are so many options in this complex system, and we have barely any insight into the real state of these viruses in patients. This is why I'd just move on and do trials with a variety of antivirals. Theoretically, this would be done in animal models, but we don't have these yet. We don't know how to induce the condition in an animal, do we?

If there's efficacy with an antiviral, we could understand the real pathogenesis better. But there's still the issue that we'd need real confirmation that the pathogenesis is destroyed and not just interrupted.

Imagine something like high dose Vitamin C in a trial and when it works, it might only resolve the pathophysiology and not the pathogenesis, but even enhance the pathogenesis by suppressing cytotoxicity of the innate immune system. And this despite of the initial symptom improvement.

 

[sometexan84]

I don't doubt the Enterovirus data as much as a doubt the herpes virus data. In most studies on herpes viruses, inappropriate biomarkers were used, from today's perspective, thereby making the end result very insensitive to the representation of real reactivation pathology. Historically, it's understandable. This is why we have to take older studies with a grain of salt.

But to be fair, I actually noted all of that when putting the data together.

That data summary I did isn't perfect, but I was as meticulous as I could be. It should be the most accurate representation available, I spent a lot of time on it.

For instance, this 1994 EBV study, I didn't include it, because VCA IgG was used as their primary measurement.

This one for Enterovirus I didn't use because they only tested for Coxsackie B4 specifically. Plus, based on those numbers, there was probably an additional reason as to why I decided to exclude it.

Still, there are so many variables involved w/ these different studies spanning decades. 100% accuracy would be close to impossible.

But I did review every single study, so I wouldn't be just blindly trusting numbers. And again, I had no bias at all at this point in time.

And while a single study might be a bit flawed in some way... you put together 10 studies, (theoretically) the average of those results should be much closer to the truth.

It's like this one story, w/ a ship wreck or plane crash in the ocean, I can't remember. Anyway, they didn't know where, and they had all these mathematicians trying to figure out the coordinates. They were all wrong, but when they averaged them together, they found the wreckage.

 

[sometexan84]

Interferon is potently antiviral for coxsackievirus B. Unfortunately when you stop the interferon, the virus and the ME/CFS returns some time later, but the remissions can last for up to a year or so.

Regarding that, I tried to illustrate the (potential) reason for this, with the different types of interferon, etc in this thread...

https://forums.phoenixrising.me/thr...eal-and-hanson-2021.84191/page-8#post-2358392

Hopefully, it makes sense