Can ME/CFS rates following LC/Covid tell us something about the immunology of ME/CFS?

For this thread I will be working under the assumption that ME/CFS is rarer following later subsequent Covid infections than it is following initial infections (think of something that the probability for someone healthy to develop ME/CFS after a Covid infection is like flipping an unfair coin, the first time around his probability of developing ME/CFS could be somewhere around 0.001 whilst for the 5th infection it might only be half as big, i.e. around 0.0005). That is to say we are not discussing the cumulative risk. From what I can gather, I think this is the potentially more interest case. It is hard to get any good data on this as the quality of research in the field has been very poor, but I haven’t seen data suggest the opposite. Nonetheless it is of course a strong assumption (which however the whole world seems to have made).

I think this might be worthy of a discussion since the other virus typically associated most strongly to an ME/CFS onset in studies is EBV and most people only tend to suffer from glandular fever once, or at least not as often as we are and will be affected with SARS-COV-2 and as such, these effects are harder to witness. Similarly I am not aware of people developing ME/CFS after having had Q-fever multiple times and other people that developed ME/CFS after an infection will likely often not know what said infection was, nor whether they had previously been infected with it.

There are many plausible reasons why later subsequent infections would lead to a lower rate of ME/CFS per infection:

• There is a saturation effect. Something along the lines of “Those that are more likely to develop ME/CFS, have already been developed ME/CFS”. This effect could for example be driven by genetic factors that tie ME/CFS to viral infections or as @Trish mentions below could be some environmental predispositions we don't know about.
• Covid infections could lead to a heightened risk of ME/CFS via a second (indirect) factor that is more prominent in initial infections than in later infections. For example an episode of glandular fever might be more likely after initial Covid infections. If a gradual fever episode is more common after initial Covid infections it’s possible that this contributes to a heightened ME/CFS risk via such factors.
• Severity of initial infections. This is something I am extremely sceptical about, as no data suggests that severity of Covid infection is tied to a ME/CFS type Long-Covid. Quite the opposite appears to be the case, with severe cases and hospitalised cases rather reporting PICS, lung damage, tissue damage etc. However, it is also entirely possible that ME/CFS can’t be picked up in such studies if the factors that tend to lead to more severe acute Covid infections (male sex, older age, heightened BMI) are opposed to precisely those factors that tend to be reported to lead to a heightened risk of ME/CFS. Or if there are some protective genetic factors that increase the risk of one but lessen the risk of the other and as such to get “clean” data one would have to account for this in an analysis. It would also be possible that the term severity as used for acute Covid infections to differentiate between ICU ventilated, hospitalised and milder infections doesn’t play a role in development of ME/CFS, but that for example it does make a difference whether one has a stronger symptomatic or weaker symptomatic or even asymptomatic infection in a susceptible individual (whatever that may mean). With the epidemiological research on Long-Covid being of the poor standard it has been, it appears unlikely that one will ever get any useful data here.
• Aditionally complex interactions of the above things could explain differences.

Suppose we assume that none of the above factors in combination would be able to explain a reduced rate of developing ME/CFS following Covid infections as time progresses. I don’t think this is necessary a reasonable assumption, I think it simply may be the more fruitful case to discuss for now. Since the case where for example DecodeME deliver clues and risk factors, ME/CFS research is anyways already in the luck.

Under such assumptions what could this tell us about the immunology of ME/CFS? If we suppose ME/CFS was for example triggered by an innate T or NK cell response are there reasons that explain why the risk of this occurring would decrease relatively per infection? Who would this fit in with something like “An Update of a Theory”?

 

Yes. The assumption that is being made here is that such a drop in probability is not fully explained by things such as genetic predisposition. Not because there is a logical reason to make such an assumption, but simply because if something like DecodeME finds a meaningful genetic predisposition, ME research will anyways be in a better position than before.

I'm not really able to understand how lifestyle factors such as rest, diet, poor housing would affect a drop in probability for subsequent infections. They hypothetically might decrease the risk of devloping ME/CFS but I would think they should do so uniformly across all infections.

 

That's a really important question. I used to think it was probably the case, but now my instinct's against.

It seems very likely that repeated overexertion can cause worse (sometimes drastically worse) ME/CFS, at least in susceptible individuals. I'm less convinced it could actually trigger ME in someone who wouldn't otherwise have developed it.

 

I did ART for 6 years post initial viral infection. I could have laid still for the next 20 years and still developed delayed PEM once I started living a normal life and doing low impact exercise again. I feel that M.E was already in the cards from the day I contracted the initial virus.

Perhaps if I was treated with anti-viral early on I might have had a chance?