Distinguishing features of Long COVID identified through immune profiling, 2022, Klein, Iwasaki et al

Distinguishing features of Long COVID identified through immune profiling
Distinguishing features of Long COVID identified through immune profiling | Nature


eta:
various outlets have articles
Scientists edge closer to finding a biomarker for long Covid, which could lead to better tests and treatments | CNN

 

This was published in Nature… impressive (I think).

 

https://twitter.com/user/status/1706367055153291636

 

Thread with summary of findings.

https://twitter.com/user/status/1706332965792272722

 

Quite a few changes from the Aug 22 pre-print. More patients enrolled from the two original locations and an independent external cohort to provide some selected comparisons. There are now multiple 2023 references too. This paper reads very well and I expect it will be featured frequently in the general and scientific media in the next two weeks (already as Sly Saint noted above). I hope it is emphasised that the biological data shows no need for any psychological explanations, and that patient reports are highly congruent with these advanced immune assessments (despite BPS's #alltestsarenormal).

Will be fascinating to see what (if any) overlaps there are with the NIH intramural ME study findings, particularly with regard to the absence of demonstrated significant auto-antibody activity, but clear immune responses to reactivated EBV and VZV (though not HSV-1) and ongoing circulating immune cell changes.

The original preprint of this paper was Aug 2022, so 13 months to publication. However they obviously did more work in the interim. NIH submitted in April, so coming up on 6 months soon - I'm hoping it's published before year end. Next month would be good...

 

With regard to low cortisol, they added the following reference —

Hypocortisolism in survivors of severe acute respiratory syndrome SARS (2005, Clinical Endocrinology)

 

A couple of Twitter users have asked Putrino whether they are trying to replicate similar findings for ME/CFS to which the response has been yes.

https://twitter.com/user/status/1706474621816463651


https://twitter.com/user/status/1706457748647370753

 

Interview with David Putrino by @dave30th

https://www.youtube.com/watch?v=qeTTjH30CDU

 

Critique/discussion of the Nature article (Distinguishing Features of Long Covid Identified Through Immune Profiling)

Starts at 16:00 minutes in (episode 1048 of TWIV https://www.microbe.tv/twiv/).

 

Not sure what if any relevance this could have. As always, potentially this is something that could be elevated in early ME/CFS that normalises in longer term, established disease.

Fluge/Mella study Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome (2016, PLOS ONE). The 2011 study that some of these patients were drawn said - "The mean CFS disease duration was 5.1 years in the Rituximab group and 8.1 years in the Placebo group, with maximum disease durations of 13 and 18 years, respectively."

---
A few papers related to APRIL (BAFF = B cell activation factor, APRIL = A proliferation inducing ligand) —

BAFF and APRIL: A Tutorial on B Cell Survival (2003, Annual Reviews)

Cracking the BAFF code (2009, Nature Reviews Immunology)

“APRIL hath put a spring of youth in everything”: Relevance of APRIL for survival (2009, Journal of Cellular Physiology)

 

Commentary in Immune system perturbations in patients with long COVID (2024, Trends in Molecular Medicine)

 

Criticism of the single-time point cortisol measurement in Is Low Cortisol a Marker of Long COVID? (2024, The American Journal of Medicine)

 

I haven’t read this as been too poorly for a while now.

but I’d like to make the point that if someone is looking at cortisol then:

1. it needs to have a synacthen test to check basal (which fir healthy people will definitely relate to time of day- issue fir us us the travel and doing it makes it big exertion) and vitally the ‘PEAK’ cortisol after the injection .

These people aren’t doing this for a reason - it’s appalling because they are potentially leaving in people whose peak is stunted and talking about their data as if that could ever change. You can’t treat and lump in busted adrenals or pituitary with those that aren’t. Or assume ‘the cause is trainable’ instead of making that assessment medically with medical staff - these MEDICAL findings aren’t for them or us to assume based on extrapolated papers done on people without this condition to disappear what actually needs to be properly ruled out the right way.

This needs to be done ‘within person’ and the difference between that ‘basal’ (in ill person it is actually‘how much are they using/needing just to be there for that test’ and annotating if it’s lying down, involved a commute etc) and the ‘max’ . The point being if there isn’t much difference that person has no spare ALL the cortisol they can get is just enough to do that test in that condition

it’s relevant because we have an illness/something wrong and there might well be some in that subgroup who actually have a condition that means their body CANT increase cortisol

2. so if what these people are thinking they are testing us the usual ‘training that works for well people’ which this sounds like they need to exclude those with a physical cortisol deficiency not by THEIR hypothesis but by the medical tests first. So they are polluting the rest with x% because doing so is convenient to do because tiny effects over bigger samples are accepted by crap oversight for journals. It’s

It’s like then being allowed to test behavioural things for blood sugar without excluding type 1duabetucs who can’t produce insulin first. And getting away with having 10% diabetic thrown in to drag down changes and create an effect they claim for the whole sample.

I cant emphasise enough how worrying it is that these standards of checking the max output of adrenals is - and that vs their baseline measure (which will include how ill and exerted we are just being there for test)

PARTICULARLY if they are using ‘change in cortisol’ as a measure

because max cortisol is literally someone’s ceiling ‘effect’ physiologically

CBT or anything else cannot heal a busted adrenal anymore than it can type 1duabetes.

the only way someone with this issue (basal cortisol = max cortisol) can avoid crisis is if the amount of cortisol their body needs eg to keep standing reduces to give spare beneath that max. Someone mightnt have low basal vs ‘norms’ but a problem here because they need more cortisol just to lie still - just due to how injured their body is

and no they can’t reduce that by CBT to think away the symptoms and no it’s not perception - that cortisol need is a measure if the physical stress that body is under and needing medical support to be treated for , definitely not exertion or any dangerous bps ‘exposure’ increases to exertion as if physically stressing the body more will lead to ‘fitness’ like a warped idea of HIT training principles but with ill people being harmed by the things that hurt their body instead of sprints fir well people. It doesn’t work like that where harm ‘fittens’ sick people. It just ends up with all their cortisol being used to keep them ‘alive’

I’m really worried we are letting them mix up two issues here.

these hypotheses should never be being tested on people with cortisol limitations - there will never be any more to give

and it’s very blinking dangerous someone would let teams of people who aren’t physiologists with expertise in adrenal and endocrine issues near these people. Adrenal crisis is life threatening.

the medical profession and any health system journal or institution are entirely irresponsible for signing off ethics or manifestos letting people put out nonsense a deficiency could be fobbed off and treated as if it could be resolved behaviourally

and that’s what these papers are targeting I think. Using the fact that some within these groups have real physical issues

then using tactics to temporarily increase their cortisol eg a shock or unpleasant temp at a time if day their cortisol is normally low to imply their health git ‘a boost’ gif a subjective answe. But that doesn’t train a busted adrenal system long term it just rigs the results short term. ?

 

5mg fir 4weeks isn’t that small or short a dose, particularly if you were insufficient fir your needs (basal near max) already. Prednisone is strong with some charts saying 5mg is equivalent to 20mg hydrocortisone

I wouldn’t be surprised if they could produce an effect if they didn’t taper someone and just stopped the 5mg and measured them a week later. That’s not the same as lifetime or even a few months later tho

I can add that you’d normally wait 4months after tapering to zero (and ive personally done from 5mg of prednisolone very very slowly - it can come in 1mg tabs) before doing a synacthen.

any medical testing facility will not only be checking fir anything that has steroids in but also hormones - and if it has to be taken then it’s calibrated which they have the charts to do. So these just wouldn’t happen because there is a protocol where it is the proper departments testing for it.

so what’s more shocking is if either researchers OR medical facilities aren’t doing these basic protocols which are standard . And were always out there

but I suspect that fir at least a decade someone was briefing to the contrary


It sounds like another condition being minimised

why the heck was no one asking why it was a bunch of unqualified specialisms doing this and not following the protocols thise specialist who should have been doing it would have?

no psych or CBT professor can safely test if some does or doesn’t have addisons or cushings or what adrenal insufficiency is. They certainly aren’t looking to be safe or follow medical protocols. So why was all this allowed?

 

And that’s despite the deliberate push to add them first given by bps and the tendency for gp to have misdiagnosed - both of which are misdiagnoses saying only things about the medic and medical system. So if even with this ‘penalty’ ne/cfs comes out lower that says it all about how naughty claims to the contrary are

 

So pleased to see finally housebound visits

if any of these measures are to be done it needs to not be a severe person dragged to travel to a hospital and collapse during the test . We know we are severe and we know that just attending a test means they are measuring us at a point way beyond our limits and then comparing us to mayber milder people who aren’t when they do those tests as if it’s like fir like

or worse we make all the effort and become drop outs so even travelling so there is evidence our debilitation exists in the hop of ‘something changing’ and the future being more possible we can end up with that not counting because we couldn’t complete some element or the tests were so out of whack etc

what hope can there be when we are this debilitated and then that means our existence of that debilitation just disappears or when we try and say it isn’t believed because there can be no proof (if we can’t do the exertion to get to somewhere that will write down how ill we are)

just to feel we could be documented and exist and people can stop doubting that existence because we aren’t present and strong enough to challenge them would be a peace of mind it is hard to describe vs feeling like no one acknowledged or knew all we went through is such a grim cruel twist (to be like we were never here or worse have our narrative rewritten as ‘I don’t know why they chose that’)