Preprint Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID, 2023, Liu, Prusty et al

If we're talking about healthy but moving very little, there definitely are lots of people who could be tapped for this. Anyone with paralysis or significant mobility issues but no systemic symptoms would provide good comparisons.

Of course they are much harder to recruit and involve, which is likely the main barrier. There is really no system to do this at scale, which is completely bizarre this late in the game.

 

I think I probably phrased things poorly in a hurry to post that between tasks in the lab. You're of course correct.

What I mean to say is that I think LC represents potentially either, or both of, the following:

1) Something similar to, or potentially the same as, ME/CFS, but with a different trigger than other, previous, forms of ME/CFS (if we take into hand the idea that different triggering events are likely to cause different but related molecular manifestations. This idea may not be true but is just something I have been mulling over of late).

2) Something similar to ME/CFS but rather in the early stages of disease. Although I should look for literature about molecular research done in recently afflicted pwME. Any pointers? I am thinking along this angle also because my own ME/CFS cohort in the lab have mostly had it for a long time and this hasn't escaped our notice. Were discussing it today.

Your point about post-infection controls is very important as well. We are trying to address this with post-COVID "recovered" samples as well as Long-COVID.

I'll cut it short here not to hijack from this paper that is about more than just LC, but Sarah is going to share our prelim LC data at IACFSME in NYC in late July so hopefully that is useful for this discussion.

I have also not had time to read Prusty's paper in more detail than a 15 minute scan so these are just my gut interpretations based on a superficial appraisal of the overall trends. It's why I haven't referred to specific results. There's so much going on in the paper that I would need many hours and a lot of notes to tease it out.

Edit: also just reiterating these are only musings, I don't want anybody to run away saying X disease is or isn't like Y disease because this scientist said so on a forum!

 

Just an additional thought, though it's late and this may not be well thought through.

While bearing in mind that LC is the patient-coined term and that the disease that frequently followed SARS-CoV-1 was simply called "ME/CFS", I'd also consider throwing in a third option (although it's something of a combo of 1 and 2 above): that LC is "ME/CFS+". By that I don't mean that LC is worse than ME (I've seen that idea promoted and it's very poor framing that largely ignores what ME is), just that it has some additional features. It may be that any particular virus that starts the ball rolling takes effect by allowing/encouraging our resident viruses (eg EBV/HHV-6) to partially reactivate and evade the immune system, and cause the disease we know as ME/CFS. Once in train, the inciting virus need not be part of the chronic picture ("hit and run").

However, this SARS2 virus has some other features, eg in relation to spike interaction with ACE2R and its effects on endothelium, clotting etc. Spike protein seems quite pathogenic by itself. Possibly there is additional SARS viral antigen persistence. Those features and related lab findings may be throwing us off the track for what's important in the pathogenesis of LC/ME/CFS.

 

This is the only study I can think of—it tests young people before they develop ME symptoms and then again afterwards. It's looking at the potential links between infectious mononucleosis/glandular fever and ME. I don't have enough knowledge to understand whether their blood test results would be useful to someone asking a different question, though.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510613/