Preprint Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19-associated ME/CFS, 2024, Anft

Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19-associated ME/CFS

Moritz Anft, Lea Wiemers, Kamil Rosiewicz, Adrian Doevelaar, Sarah Skrzypczyk, Julia Kurek, Sviatlana Kaliszczyk, Maximilian Seidel, Ulrik Stervbo, Felix S. Seibert, Timm H. Westhoff, Nina Babel

doi: https://doi.org/10.1101/2024.09.25.24314345

https://www.medrxiv.org/content/10.1101/2024.09.25.24314345v1

Abstract

Autoreactive antibodies (AAB) are currently being investigated as causative or aggravating factors during post-COVID.

In this study we analyze the effect of immunoadsorption therapy on symptom improvement and the relationship with immunological parameters in post-COVID patients exhibiting symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

This observational study includes 12 post-COVID patients exhibiting a predominance of ME/CFS symptoms alongside increased concentrations of autonomic nervous system receptors (ANSR) autoantibodies and neurological impairments.

We found that following immunoadsorption therapy, the ANSR autoantibodies were nearly eliminated from the patients' blood.

The removal of IgG antibodies was accompanied by a decrease of pro-inflammatory cytokines including IL4, IL2, IL1β, TNF and IL17A serum levels, and a significant reduction of soluble spike protein.

Notably, a strong positive correlation between pro-inflammatory cytokines and ASNR-AABs β1, β2, M3, and M4 was observed in spike protein-positive patients, whereas no such correlation was evident in spike protein-negative patients. 30 days post-immunoadsorption therapy, patients exhibited notable improvement in neuropsychological function and a substantial amelioration of hand grip strength was observed.

However, neither self-reported symptoms nor scores on ME/CSF questionnaires showed a significant improvement and a rebound of the removed proteins occurring within a month.

 

Now published in Molecular Therapy:

Link | PDF (open access)

 

I think members can see what things are wrong with this paper but just in case new members are unfamiliar with all the pitfalls and might be encouraged by it I will chip in with the usual comment that it tells us nothing.

The title should not include the word 'effect'. Some improvements are reported - although the subjects apparently didn't feel better (!!) - but there is no reason to call these effects without a controlled observation. Improvements would have been expected without the treatment.

 

Even without a control group, we do see that these may be real effects of the intervention, since they rebounded afterwards:

I don't know if any of that is actually relevant, though. Why would IgG removal decrease spike protein in the blood, and only temporarily?

And though self-reported symptoms didn't improve, these did:

Like you said, it doesn't mean much without a control group, but I'd like to see it followed up with a controlled study.

 

Of course there were real effects on antibodies because that is what the treatment can be expected to do, but that is not an effect on clinical presentation (OK it is an effect on antibodies but you can't put the two together).

It is a bit like anti-IL-6 receptor, which blocks CRP production. CRP levels are usually a good guide to how bad rheumatoid is clinically but if you give anti-IL-6R and CRP goes down you have proven nothing in terms of an effect on clinical rheumatoid. The CRP is not itself the inflammation but an after effect of inflammation. So the inflammation could be just as bad but the CRP zero.

 

Well, spike protein too. Do you know why that would happen?

Edit: From discussion about spike protein findings:

So likely just: "However, since high titers of SARS-CoV-2 spike protein specific antibodies were detected in all patients, it is likely that these antibodies bound to soluble spike protein, leading to their removal along with the antibodies during IA-therapy."

 

If the patient had any anti-spike protein antibody, as is likely, then it would presumably come out with the antibody. I don't think it tells us anything useful.

In other words maybe they should have 'expected'.