Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro, 2022, Flaskamp et al

[LarsSG]

Abstract
A proportion of COVID-19 reconvalescent patients develop post-COVID-19 syndrome (PCS) including a subgroup fulfilling diagnostic criteria of Myalgic encephalomyelitis/Chronic Fatigue Syndrome (PCS/CFS). Recently, endothelial dysfunction (ED) has been demonstrated in these patients, but the mechanisms remain elusive.

Therefore, we investigated the effects of patients’ sera on endothelia cells (ECs) in vitro. PCS (n = 17), PCS/CFS (n = 13), and healthy controls (HC, n = 14) were screened for serum anti-endothelial cell autoantibodies (AECAs) and dysregulated cytokines. Serum-treated ECs were analysed for the induction of activation markers and the release of small molecules by flow cytometry. Moreover, the angiogenic potential of sera was measured in a tube formation assay. While only marginal differences between patient groups were observed for serum cytokines, AECA binding to ECs was significantly increased in PCS/CFS patients.

Surprisingly, PCS and PCS/CFS sera reduced surface levels of several EC activation markers. PCS sera enhanced the release of molecules associated with vascular remodelling and significantly promoted angiogenesis in vitro compared to the PCS/CFS and HC groups. Additionally, sera from both patient cohorts induced the release of molecules involved in inhibition of nitric oxide-mediated endothelial relaxation. Overall, PCS and PCS/CFS patients′ sera differed in their AECA content and their functional effects on ECs, i.e., secretion profiles and angiogenic potential. We hypothesise a pro-angiogenic effect of PCS sera as a compensatory mechanism to ED which is absent in PCS/CFS patients.

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[marcjr]

I would not be surprised if this was also connected to GPCR autoantibodies, just like this paper from early this year points out:
Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients
https://pubmed.ncbi.nlm.nih.gov/35074481/

They did not seem to have a panel for those in this paper, we do have these AECAs though.
Shouldn't we, at least anecdotally, be seeing more success stories involving patients undertaking plasmapheresis or immunoadsorption, given these are commercially available? I've seen a mixed bag of reviews involving people that have gone through these.

 

[Andy]

Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients
https://pubmed.ncbi.nlm.nih.gov/35074481/

Our thread on that paper, Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients, Bertinat et al (2022)

 

[Andy]

We hypothesise a pro-angiogenic effect of PCS sera as a compensatory mechanism to ED which is absent in PCS/CFS patients.

It would be interesting if it was possible to follow these two groups to see how they end up long term, perhaps they have found what differentiates those who recover eventually and those who don't.

 

[FMMM1]

I would not be surprised if this was also connected to GPCR autoantibodies, just like this paper from early this year points out:
Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients
https://pubmed.ncbi.nlm.nih.gov/35074481/

They did not seem to have a panel for those in this paper, we do have these AECAs though.
Shouldn't we, at least anecdotally, be seeing more success stories involving patients undertaking plasmapheresis or immunoadsorption, given these are commercially available? I've seen a mixed bag of reviews involving people that have gone through these.

Haven't read the posts here or the abstract - so a few standard comments from me!

I would have thought that what's more worrying is that rituximab, i.e. a go to treatment didn't work - not sure if "plasmapheresis or immunoadsorption" are really go to treatments for autoantibody/autoimmune diseases. So anyone proposing pathological/ME/CFS causing autoantibodies has to explain why rituximab didn't work. By the way rituximab wipes out your antibody producing B-cells although I recall discussion on whether long lived (not affected by rituximab?) plasma cells could still be producing pathogenic autoantibodies.

Another thing is that I'd like some evidence that the test they used (to detect autoantibodies) is actually reliable - oh and even if you have detected autoantibodies, it appears that slightly elevated levels aren't necessarily pathogenic.

Haven't read the paper/abstract though!

 

[FMMM1]

Just skimmed through the abstract and I'd be interested to see if the tested a large control group and a large ME/CFS group then would there be clear differences?
I'm also wondering if the more knowledgeable would be concerned that the differences are artifacts of the technique - perhaps testing a larger cohort would help to establish if this is real.

++GWAS - any supporting evidence for this?

https://pubmed.ncbi.nlm.nih.gov/35074481/

 

[Amw66]

Just skimmed through the abstract and I'd be interested to see if the tested a large control group and a large ME/CFS group then would there be clear differences?
I'm also wondering if the more knowledgeable would be concerned that the differences are artifacts of the technique - perhaps testing a larger cohort would help to establish if this is real.

++GWAS - any supporting evidence for this?

https://pubmed.ncbi.nlm.nih.gov/35074481/

Perhaps eNOS genes ?