COVID-19 patient fibrinogen produces dense clots with altered polymerization kinetics, ... increased sialic acid, 2022, Moiseiwitsch et al

COVID-19 patient fibrinogen produces dense clots with altered polymerization kinetics, partially explained by increased sialic acid
Moiseiwitsch N, Zwennes N, Szlam F, Sniecinski R, Brown A

Background: Thrombogenicity is a known complication of COVID-19, resulting from SARS-Cov-2 infection, with significant effects on morbidity and mortality.

Objective: We aimed to better understand the effects of COVID-19 on fibrinogen and the resulting effects on clot structure, formation and degradation.

Methods: Fibrinogen isolated from COVID-19 patients and uninfected subjects was used to form uniformly concentrated clots (2 mg/mL), which were characterized using confocal microscopy, scanning electron microscopy, atomic force microscopy, and endogenous and exogenous fibrinolysis assays. Neuraminidase digestion and subsequent NANA assay were used to quantify sialic acid residue presence; clots made from the desialylated fibrinogen were then assayed similarly to the original fibrinogen clots.

Results: Clots made from purified fibrinogen from COVID-19 patients were shown to be significantly stiffer and denser than clots made using fibrinogen from non-infected subjects. Endogenous and exogenous fibrinolysis assays demonstrated that clot polymerization and degradation dynamics were different for purified fibrinogen from COVID-19 patients compared to fibrinogen from non-infected subjects. Quantification of sialic acid residues via the NANA assay demonstrated that SARS-Cov-2-positive fibrinogen samples contained significantly more sialic acid. Desialylation via neuraminidase digestion resolved differences in clot density. Desialylation did not normalize differences in polymerization, but did affect rate of exogenous fibrinolysis.

Discussion: These differences noted in purified SARS-Cov-2-positive clots demonstrate that structural differences in fibrinogen, and not just differences in gross fibrinogen concentration, contribute to clinical differences in thrombotic features associated with COVID-19. These structural differences are at least in part mediated by differential sialylation.

Link | PDF (J Thromb Haemost)

 

Well it could be a survivor effect. We're still looking at LC patients at most not quite 3 years in. Perhaps there are many people who were never able to "graduate" to being long-term ME patients. Perhaps the hypercoagulation could be a stage, which itself can resolve but leave the patient with metabolic compensations that are stuck or degrade further.

But more likely is that the hypercoagulation is a feature, but that it's alongside, if not mostly induced by, immunometabolic derangement, rather than being the sole cause as proposed by Pretorius et al. Perhaps this particular virus is especially damaging to vascular and thrombotic systems, hence all the cardiovascular complications and sudden deaths we're currently reading about.

This week they've published a new paper which doesn't add much more I think, in terms of their overall theory. What we would need to see is replication from other teams, using different methods. I'm still very keen on amyloid fibrinogen as an important idea for a number of diseases. I guess we wait for the teased replication from the Manchester team. The new paper does provide evidence for antibodies / autoantibodies within the microclots. This is something I've been interested in as a potential explanation in the progression of autoimmune/other chronic disease, but I have limited knowledge. I do think antibodies might tend to stick to clots anyway so this might be mostly artifactual, but I will be keen to hear other expert opinion on this.

Will be interested in your and others' thoughts on that paper, if anyone gets a chance.

 

Perhaps applicable relative to this thread from Twitter. If this thread has veracity it is worrying .
Clots in placentas

https://twitter.com/user/status/1573320233347338240