Hypothesis The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome, 2023, Maureen R. Hanson

The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome
Maureen R. Hanson

Sections —

• Can any infection lead to ME/CFS?
  
• Why is the enterovirus family the most likely culprit in ME/CFS?
• What is the relationship between human herpesviruses (HHVs) and ME/CFS?
• Should the post-SARS-CoV-2 infection syndromes be called “ME/ CFS”?

Link | PDF (PLOS Pathogens)

 

I've never understood why John Chia's enterovirus findings are not considered credible. If they were considered credible, would there not have been more attempts to replicate them?

 

Seems to be a general problem in the post-viral illness field. No one wants to do this type of work and funding isn’t the main reason. It seems to be the case for MS as well. One would have thought that someone would have at least tried to replicate and refine Ascherio’s big MS and EBV findings, but seems like no one has even tried to do so in the last 2 years.

 

The first sentence of the section “Can any infection lead to ME/CFS?” reads “There is actually no proof that multiple different pathogens can cause ME/CFS.” Yet, the review on post-acute infectious syndromes by Choutka, Iwasaki et al that was published last year in Nature Medicine extensively documented the opposite. We also now have some published evidence showing the conversion of acute infection with SARS-CoV-2 to ME/CFS. Hanson’s piece therefore seems based on a false premise.

Edit: this piece was funded in part by the TEMPI foundation launched by Christoph Stroeck, a very severe Austrian ME/CFS patient, with the help of his family. It is disappointing to see that they align themselves with the deprecated hypotheses put forth in this paper, although I believe Stroeck has often tweeted about this topic.

 

Looked at a few sentences. The reference to "Have they induced autoimmunity through molecular mimicry?"* presumably relates to the recent findings that EBV likely causes most (97%?) cases of MS - US Army study. The proposed mechanism is "molecular mimicry" resulting in the production of autoantibodies - B-cell autoimmunity. However, rituximab didn't work in ME/CFS so that proposed mechanism isn't supported by the evidence currently available. Autoimmunity/autoantibodies could still be a cause of some cases of ME/CFS and to me that would be interesting e.g. identification of pathway which is also relevant in non-autoimmune cases.
Also, B-cell autoimmunity, in MS, has a genetic signature - certain SNIPs [HLA?] occur at much higher levels in people with MS. Therefore, if you didn't know that MS was an autoimmune disease, but you had genetic [GWAS?] data, then the genetic data would tell you that it was an immune disease. Problem is ME/CFS is likely much more heterogeneous than MS so the genetic clues may be harder to find. In dementia it's taken [EDIT - multiple] large GWAS studies to find relevant genes.
EDIT - roll on release of data from Ron Davis's NIH funded HLA study & results from UK GWAS (DecodeME)

*"
Conclusion
Ignoring the abundant evidence for EV involvement in ME/CFS has slowed research into the possible dire but hidden consequences of EV infections, including persistence in virus reservoirs. Prior to the SARS-CoV-2 pandemic, the ability of RNA viruses to persist in tissues for long periods was largely ignored. Further, recognizing that EVs are prime candidates for causing ME/CFS suggests how critical it is to pursue a relevant inquiry into this diverse virus family. Do hidden reservoirs harbor these viruses? Have they induced autoimmunity through molecular mimicry? Is it past or current infection that has resulted in the many findings of immune dysfunction in ME/CFS?"

 

I find this an extremely strange paper. My only explanation is that this paper has to be part of some larger grant proposal to study the role of Enteroviruses in ME/CFS or that TEMPI funded a paper specifically on Enteroviruses or wants to focus on this, possibly due to Christoph’s background.

“Should the post-SARS-CoV-2 infection syndromes be called “ME/CFS”?”

Is a very strange heading. I’ve never seen anybody credible say that “Long-Covid” should be called “ME/CFS”. The only thing we know is that Long-Covid is an extremely heterogeneous illness and many people with Long-Covid also meet every criteria for ME/CFS (there’s tons of studies on this, see Carmen Scheibenbogen’s work), whilst many other Long-Covid patients, even the majority, don’t meet the ME/CFS criteria. We’re all against this “One Name Campaign”.

However, the argument that SARS-COV-2 might not be causing ME/CFS if this person fulfils every diagnostic criteria, because the diagnostic criteria pre-date the Covid-19 pandemic I find rather unusual. Would a cancer researcher say “we discovered a new type of cancer, but we can’t call it a cancer because that word predates what we found”?

I think it’s fair to say that if someone has Long-Covid with ME/CFS that it’s currently also fair to say exactly that, with a large focus on the Covid infection, but without neglecting the outcome. Of course the specific onset could be of vital importance and has to be incorporated into any diagnosis and study. Of course, one should also consider the full spectrum of an illness, but to say EV’s cause ME/CFS, but other viruses can’t, because that’s how I define ME/CFS is rather unusual.

We have longitudinal studies of people that were healthy prior to a SARS-COV-2 infection and now meet ME/CFS criteria. Their symptoms overlap with those that have ME/CFS from MERS-SARS. The only difference from past to presence is that there is now a global pandemic causing a post-viral illness that seems harder to ignore than a smaller outbreak or the loss of a single persons life. The current data shows a direct Covid-19 & EBV & ME/CFS link. I haven't seen such a link for Covid-19 & EV & ME/CFS. So whilst there might be differences, I certainly wouldn't neglect the Herpesvirus connection.

I think Long-Covid has to be studied separately and things shouldn’t be mixed up, i.e. doing something like adding ME/CFS patients to the data as "controls" rather than considering everything to be the same is the way forward, the “One Name Campaign” is a horrendously bad idea, but this paper seems to do what every patient has been criticising for the past 4 years: It neglects past evidence, research and knowledge. Apart from some researchers, for example Carmen Scheibenbogen, a majority of ME/CFS researchers and research organisations failed to incorporate their knowledge into Long-Covid, or at least attain research grants specific to study Long-Covid. Together with HIV researchers, post-Ebola researchers and immunologists they should have been at the forefront of studying Long-Covid, but instead have been overtaken by newer organisations.

 

I think it is plausible that enterovirus infection is a necessary mediating factor in significant proportion of people diagnosed as ME. I think it would probably be a 'permissive' factor rather like H pylori. Both are almost everywhere but may still be necessary for the respective illness. I wouldn't put a bet on it but I would not exclude it.

The problem for me with this review is that the case being made is not well built. The Royal Free epidemic produced signs suggestive of brain or spinal cord injury acutely but as far as I know in the long term no case was validated as encephalomyelitis. So this acute outbreak is really a red herring. ME as currently understood does not include features suggestive of brain or cord injury.

Also if Ross River Virus is to be excluded because it is local and rare then whatever caused this very unusual outbreak at the Royal Free should probably also be excluded in that it is equally unlikely that it is the cause of even 1% of ME cases since. If it was still widely circulating why are there no outbreaks of encephalomyelitis?

 

“I think it is plausible that enterovirus infection is a necessary mediating factor in significant proportion of people diagnosed as ME.”
Me too.

@Jonathan Edwards What would be “features suggestive of brain or cord injury.?”

————-

Ps
Can someone tell me what the “One Name” stuff refers to?
I can’t read this paper cause I’m exhausted.

 

Wasn't polybio all about replicating those tissue viral studies? They got a ton of money too. What happened to that?

 

I remembered that she also gave a talk presenting the same ideas a couple of years ago, I think at one of the OMF-conference but I'm not quite sure.

 

I'm sure the many Australians suffering from post-viral problems following Ross River Fever would be quite surprised to read this. Some don't meet ME/CFS diagnostic criteria but there are plenty in local ME/CFS support groups who do.

This recent newspaper article comes to mind:

 

If a particular disease pathology is common in ME/CFS* then I assume it should turn up in GWAS. However, diseases like dementia have required the combination of several large [GWAS] studies i.e. to identify genes & thus help to focus research. Presumably there are different forms of dementia & thus th genetic signals are "diluted".
I wonder if there's a way to test the enterovirus hypothesis? E.g. "H pylori" is treated using antibiotics & John Chia did claim to have cured people using antivirals - correct?

*Jonathan -
"I think it is plausible that enterovirus infection is a necessary mediating factor in significant proportion of people diagnosed as ME. I think it would probably be a 'permissive' factor rather like H pylori. Both are almost everywhere but may still be necessary for the respective illness. I wouldn't put a bet on it but I would not exclude it."

 

Slight distraction but there's been a (recent) significant breakthrough/s re mosquito borne diseases --- two vaccines have show efficacy [80% ish?] against malaria. If those techniques are applicable to Ross River virus then it may be interesting i.e. to see if there is a link between that virus & ME/CFS type illness e.g. common pathology/disease mechanism?

 

I’d go further and call it misguided, pointless and probably harmful.

 

From a tweet from Christoph