Hypothesis The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review, Hanson et al (2021)

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease whose etiological basis has not been established. Enteroviruses (EVs) as a cause of ME/CFS have sometimes been proposed, as they are known agents of acute respiratory and gastrointestinal infections that may persist in secondary infection sites, including the central nervous system, muscle and heart. To date, the body of research that has investigated enterovirus infections in relation to ME/CFS supports an increased prevalence of chronic or persistent enteroviral infections in ME/CFS patient cohorts than in healthy individuals. Nevertheless, inconsistent results have fueled a decline in related studies over the past two decades.

This review covers the aspects of ME/CFS pathophysiology that are consistent with a chronic enterovirus infection and critically reviews methodologies and approaches used in past EV-related ME/CFS studies. We describe the prior sample types that were interrogated, the methods used and the limitations to the approaches that were chosen.

We conclude that there is considerable evidence that prior outbreaks of ME/CFS were caused by one or more enterovirus groups. Furthermore, we find that the methods used in prior studies were inadequate to rule out the presence of chronic enteroviral infections in individuals with ME/CFS. Given the possibility that such infections could be contributing to morbidity and preventing recovery, further studies of appropriate biological samples with the latest molecular methods are urgently needed.
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https://www.frontiersin.org/articles/10.3389/fmed.2021.688486/abstract

 

To me, the lack of a definite 'all PWME have this virus' finding means that ME is not a viral disease. Viral infections might trigger ME in people susceptible to developing ME, and might increase the severity in PWME who are susceptible to that, but that there are also other PWME who triggered from other factors and who don't have a chronic viral infection or hidden viral fragments or other excuses for why a guilty virus can't be found.

If I was allocating ME research funding, viral hypotheses wouldn't be at the top of my list.

 

Pathogens of all sorts would be considered for my list of ME/CFS causes, just as they would be for MS. I fully would expect multiple infectous agents to be behind discreet ME/CFS cases, i.e, enteroviruses cause ME for some, other viruses for some, bacteria for some, parasites for some, etc.

Moreover, I'd be looking in tissue whenever possible.

 

I'm skeptical of enteroviruses as a category of pathogens, rather than pathogens with the ability to infect the GI tract. My understanding of enteroviruses is that it's a class of viruses known to do that, but viruses not in that category can still infect the gut, like Covid-19 does. And GI symptoms have been one of the strongest predictors of LC so far, although that's limited because of how little the right questions are asked.

So is that really about the family of viruses known to do that? Or any pathogen that can take hold in there, which is an overlap but not the same thing. Because that would not explain LC, or mono, for that matter. Unless it's just a chance interaction that allows an enterovirus to go into rage mode.

 

Seems promising other than the part where we can't find any evidence of viruses in anybody and the drugs used to treat them are useless.

 

Enteroviruses are known to cause diseases of the brain and heart as well as hand foot and mouth disease and summer flu. They also have mechanisms for evading the immune system. They are a seriously neglected class with the CDC taking far too long to be forced to admit that acute flaccid paralysis is enteroviral because of a conforting feeling they are not a cause of serious disease any more. Remember coronaviruses were just the common cold 2 years ago.

Viruses are way more complicated organisms to detect and study than bacteria. Fifty years ago we were taught about a type of plant virus that was just a naked piece of RNA and the lecturer said it gave him nightmares if something like that was infecting humans.

A virus that is very good at evading the immune system is a very successful virus. Causing a subclinical infection then finding a niche and causing barely noticeable ill health until it can get a better foothold if there is disruption to the body is a very good strategy.

I don't think that research funds for viruses are the way to go - actually looking at how the disease is experienced so we are all talking about the same thing is the most important thing - but there is a good chance many things that go wrong in the body are triggered by viruses.

 

I had a sudden viral onset, and whatever was occurring in my immune system during that time period seems to have activated h pylori infection. I might have been asymptomatic w h pylori for years, but the viral onset altered my immune system and brought it to surface.

Just a theory of mine of course, but a big coincidence if it didn't. My gut was increasingly becoming worse 5 years after onset until I was treated.

I don't think that it's an ongoing viral infection in my case, but an altered immune system that occurred after the initial infection.

 

The main argument for the role of enteroviruses in ME are the past epidemics where such a connection was hypothesized. But those do not seem to appear anymore and instead millions of patients got ill outside recognized epidemics, without clear seasonality etc. I haven't found a discussion on why this in the paper.

Then there is the fact that other viruses such as EBV, Ross River and perhaps also SARS-CoV-2 seems to trigger ME/CFS. The author try to deal with this objection as follows:

They also argue that:

I'm not convinced. Except for post-polio syndrome, enterovirus-related diseases seem quite different from ME/CFS.

 

Ditto my daughter.

 

Merged thread

Sorry, but I think this is a dead end. (Not necessarily a knock against Maureen Hanson, but rather against this line of research).

https://twitter.com/user/status/1438407447778111492

 

Yes, even if something is a dead end then curiousity about the condition and careful observation & documentation can still add to the knowledge base. They might even lead to further questions, opening up new avenues of research.

 

What leads you to that conclusion?

 

I think it is reasonable. The only real reason why anyone is interested in enteroviruses in ME is that way back in the time the Royal Free outbreak neurological features raised the suggestion of a novel enterovirus. But it was never found and the neurological features are not recognised today as part of ME as we know it. So it seems a red herring. People have looked for enterovirus for decades and not found anything convincing.

If there is such a thing as flogging a dead horse this might be a strong candidate.

 

I believe Dr. Chia found enterovirus in an autopsied brain donated from an ME patient. It was never detected in the patients blood or stomach tissues.

 

The main reason there are not large enteroviral epidemics anymore are because of vaccination for polioviruses. Hand foot and mouth disease still runs rampant through nurseries though and summer flu from Coxsackie B is common. In fact one of the reasons they said enteroviruses were not involved in ME is that everyone is exposed to them.

Strangely, the other reason is that outbreaks are not reported. Acute flaccid paralysis in children has been sweeping the world for a good few years now. There was speculation last year if the lockdowns would reduce the numbers but I have not seen anything since whether it has or not.

There have been epidemics of atypical polio in India that I saw mentioned too.

Not specifically about ME but there is a strange aura around enteroviruses. They are somehow considered unimportant compared to others in the way that ME is not given the same status as MS and RA. Yet they are a complex, fascinating class of virus that are worthy of study in their own right.

 

There's also the cause/effect question: is increased presence of viruses a cause of ME, or just a result of it?