Review Advocating the role of trained immunity in the pathogenesis of ME/CFS; a mini review, 2025, Humer et al

Indeed, I was misremembering.

 

One of the most common triggers of temporary improvement in symptoms I have seen in the LC community, far too common to ignore, is, ironically: illness. Has to be a mild 'cold', of course, not something that knocks them out. And it only lasts for a few days, then things go back. Of course it's not the only such trigger, but it's certainly one that significantly limits the possibilities.

I'm very certain that if those necessary conditions were perfected and applied, we could reduce the search space by a factor of easily 1000x, making it a manageable problem. All of this randomly searching around is not going to work. There are factors that need to be met, but no one seems to have bothered working those out. Maybe the expertise just doesn't exist for that, but this is obviously necessary for any competent investigation so it can't be missing entirely, it's just being misapplied.

But even the basic facts currently known completely dismiss all the psychobehavioral woowoo, and yet it remains the singular focus of fanatical obsession for most. The only search space most are willing to look into is the cul-de-sac near the pub where they prefer to hang out. For unrelated reasons that are mostly political and ideological, but still.

So most likely this is something that will only be worked out by AIs, because at its core this is human failure, not technical or limited by nature. Almost all of the ongoing research efforts are being cancelled anyway, and nothing useful has come out of it so far, so it's not as if it's likely that we see anything out of traditional research any time soon. It's too hard a problem, so hard most don't even see the problem. Those are always the hardest ones.

 

That happened to me, in the first year or so of my ME/CFS. I caught a cold and I felt EPIC. And then it was gone.

 

Another thing that your model will have to explain, @Jonathan Edwards! The weirdnesses are piling up.

 

Another n=1. I had a stomach bug about a year ago. Crashed terribly for a week, then felt great for a week, then back to normal bad.

 

As far as I understand it would be good for the model to be able to account for spontaneous improvement and spontaneous remission, but it does not have to account for spontaneous improvement after certain events as there is no indication that such events exist outside of just being random timepoints, as the timeframes of certain events occurring and improvement/remission might have just been coincidental. Perhaps someone could research whether people report more often to feel a short improvement after a viral infection but it seems such questions on S4ME have not revealed anything consistent.

 

Ditto AZ Covid vaccine. It really was EPIC for a week. Then, as you say, gone.

 

They might. But that doesn't explain why the same people report always feeling better with an infection. Or why the same thing should happen with a second dose of the same vaccine.

It could be a clue, but perhaps it's more likely to be one of those things that'll make better sense when we've got a few of the jigsaw pieces interlocked.

 

That's a fair point!

 

But is that the case? The people above have written that it happened once to them, which indicates that it is inconsistent rather than the opposite. I once asked a question about whether a specific symptom improved during viral infections and I don't remember any consistent answers, perhaps I asked the wrong question about the wrong symptom but I haven't seen any consistent answers elsewhere either.

Had it not been for a larger Phase 3 study, we'd all be arguing that Rituximab is such an event, when it now appears to not be.

 

I can handle it.

 

Yes, a proportion of patients say it is.

If it happens to you every time you pick up a bug, it's a marked change. In my case it's unusual and consistent enough that I can use it as a warning not to plan anything for the next week, because I'm coming down with something.

The reports don't only come from S4ME, people have been commenting on how strange it is for 25 years at least.

It's anecdotal, of course it is, but the entire condition's anecdotal. Unless we're going to cast doubts on people's accounts of every aspect of ME/CFS, I think we have to accept their word for it.

 

Does feeling epic mean no baseline symptoms or no PEM regardless of exertion or both?

 

When I felt great for a week after the stomach bug, I was unable to trigger the normal worsening of symptoms.

I did not overdo the physical aspects to be safe, but I used my head a lot. Like an order of magnitude more.

 

Can't answer for Sasha, but almost.

After the AZ vaccine I felt as if I could run up a mountain, while singing. I cleaned the entire house in two days, which is way outside my normal capacity. I still got burning pain in my muscles when I sat down, but I felt so great I didn't mind.

No PEM, but I recognised it for what it was and stopped pushing after the first couple of days. Normally I only get this for quite a short time, so I'd no way of knowing I'd have a whole week of it on that occasion.

 

I wish I could remember but it's nearly 40 years ago. I'd never heard of PEM and hadn't noticed it in myself (it took a family member pointing it out to make me realise my reactions to things were delayed). But I just remember feeling FAB. IIRC, I started feeling fab as soon as my nose started streaming. For the next many years, I don't remember showing frank viral symptoms like a streaming nose, just a permanent sore throat, and the epic feeling didn't come back.

 

What if we’re the rare ones and those recovering or switching are the norm? We don’t really have the data to say which way round things are. Or if people ‘recover’ without ever having been bad like us. Maybe we all had something for years before we thought we did?

The idea of a permanent changes may not fit the fluctuations and changes. Are we holding onto ideas because of our experiences?

And of course if we get into all the other many inconsistencies, just in this thread we have @Kitty describing a temporary but significant improvement from the AZ vaccine while I had hell for months and a long slog for years after the same.

There’s obviously a lot I and we all feel strongly about. But there’s also a lot I think I could give quite conflicting narratives on. I’m not sure how much of these things we really understand or how much we retrofit or will make sense in a different way if or when we have better explanations for underlying mechanisms.

I’m in a bit of an embracing uncertainty day today I think…

 

The way I see it, they're not necessarily conflicting. All they seem to be indicating is shifts that can go both ways.

I don't know anything about immunology, but it looks like one of the few plausible options for changes that are rapid, impactful, don't leave damage, and can improve the situation as well as make it much worse.

I was reminded last week how fast the onset of 'flu symptoms can be. The switch from getting my gear ready for St Patrick's Day to feverish, horizontal, and not going anywhere took three and a half hours. A few months earlier I'd had a sickness bug that started by making me feel fantastic (always happens when I have a virus), then declaring death would be preferable, then back to normal, in four days.

So what appears confusing and contradictory in ME/CFS might just be adding to the general argument for @Jonathan Edwards' immune hypothesis.