Neutralization of AAB Targeting G-Protein Coupled Receptors Improves Capillary Impairment and fatigue ... after COVID-19 Infection, 2021, Hohberger

Ryan31337

Ryan31337

Senior Member (Voting Rights)
Full title: Neutralization of Autoantibodies Targeting G-Protein Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms after COVID-19 Infection

Abstract
Clinical features of Corona Virus Disease 2019 (COVID-19) are caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial health care issue, and the development of a Long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as e.g. impaired capillary microcirculation, chronic fatigue syndrome (CFS) and functional autoantibodies targeting G-protein coupled receptors (GPCR-AAb).

Here, we present a case report of a successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with high affinity to GPCR-AAbs that neutralizes these AAbs. A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from chronic fatigue syndrome, loss of taste and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks.

This observation was accompanied by a constant improvement of the patient’s fatigue symptoms, and taste as well as retinal capillary microcirculation. This phenotype is, to the best of our knowledge, the first report worldwide of a direct cure of symptoms of LCS. Therefore, we propose that removal of GPCR-AAb ameliorates characteristics of the Long-Covid-Syndrome such as capillary impairment, loss of taste and CFS.

Open access, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3879488
 
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Snow Leopard said:
Impaired capillary microcirculation is a central part of one of my primary hypotheses. The suggestion of a ß2-adrenergic receptor autoantibody association is curious.

See also https://adisinsight.springer.com/drugs/800047946 (they mention CFS as well)
https://clinicaltrials.gov/ct2/show/NCT04192214
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Bear in mind that these autoantibody tests are notoriously unreliable. There's a thread here re a new technique which should result in better autoantibody tests
https://www.s4me.info/threads/reap-...-the-human-exoproteome-2021-wang-et-al.20747/
more here re this technique
https://www.biorxiv.org/content/10.1101/2021.02.11.430703v1
 
it is impressive they managed to help this patients blood flow problems .but for the claim of improving the patients chronic fatigue from post covid is over reaching due to natural improvements over time for the majority of long haulers .
 
Snow Leopard said:
Impaired capillary microcirculation is a central part of one of my primary hypotheses.
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I agree, it fits with some of my symptoms and we had Systrom recently deducing (from the results of i-CPETs) that there is a blockage in the capillaries and/or venules.

And we discussed the idea of retinal microcirculation as a biomarker recently too.

There is a company behind this - Berlin Cures.

It's interesting that the man developed the fatigue syndrome, lost a sense of taste and developed high blood pressure only after his second Covid-19 infection.
 
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This account is complicated though. The man was already part of a glaucoma registry at this university, and it had already been noted that the man had autoantibodies targeting the ß2-adrenergic receptor. The man had had multiple operations on one eye - teh eye the data is shown for, and a cataract in the other eye.
Being a participant of the Erlanger Glaucoma Registry (EGR, ISSN 2191-5008, CS-2011; NTC00494923) of the Department of Ophthalmology, University of Erlangen-Nürnberg, a seropositivity of AAb targeting ß2-adrenergic receptor (ß2-AAb) has already been known to preexist for 12 years.
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So, the first Covid-19 infection didn't change that (but added some more autoantibodies to the man's collection).

This is interesting - capillary vessel density. They already had data from back in 2018. That's the first red spot, followed by the decline down. There is a truncated y axis, but still, the decrease (attributed to the Covid-19 infections) is impressive. Then there is the infusion of the autoantibody neutraliser, and a subsequent increase in the measure of capillary vessel density.

Screen Shot 2021-08-20 at 5.54.10 PM.png
 
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They measured the level of autoantibodies against G-protein coupled receptors (ß2-AAb (that's the one the man had already had), AT-1-AAb, α1-AAb, MAS-AAb, M2- AAb). The infusion treatment is reported as knocking the level of the autoantibodies right down:

Screen Shot 2021-08-20 at 5.58.28 PM.png


And then there's the fatigue scores, with the man's fatigue scores improving steadily to a healthy level over the month following the infusion. It's reported that other symptoms such as brain fog also improved and went away. And his glaucoma was fixed, to the point where he didn't need to use drops. And his blood pressure decreased.

Screen Shot 2021-08-20 at 6.05.52 PM.png
 
Regarding retinal microcirculation as a biomarker:

There are only two regions in living humans, at which capillary microvessels can be scanned, monitored and quantified non-invasively: (1) nailfold by microscopy, (2) retina by OCT-A.

OCT-A is a novel technique, enabling non-invasive scans of the retinal capillary system with a high resolution (low μm range). Up to now, there is only one OCT-A device available (Spectralis II OCT- A), scanning the region of interest in three microvascular layers. Those microvascular OCT-A scans correlate well with the human anatomy 14. A previous study showed that especially in the ICP and peripapillary region a significantly decreased VD was observed after COVID-19 compared to healthy eyes.
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They suggest that altered blood cell deformability and/or endothelial dysfunction might have something to do with the reduced microcirculation seen after Covid-19. and they think that these vaso-active G-protein coupled receptor autoantibodies have something to do with it.

So, yeah, one person, no controls, unblinded, a commercial interest in finding something, other issues like possible impacts of the past operations, possible unreliable measurements of the autoantibodies. But still, interesting.
 
Is there any reason why a g-coupled receptor aa would be unaffected by IVIG or Rituximab?

Worth noting his fatigue might fall under what we call mild or very mild by me/cfs standards and was around 75 at the Bell score when he started treatment. That's pretty high tbh, I don't know how many patients would have a 75, but my guess is it's quite low. I suspect a lot of non-me/cfs post-covid fatigue is around this number, which by normal standards is very fatigued. The Chalder Fatigue score is more midrange - maybe 18/19 of 33.
 
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