SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19, 2021, Grobbelaar et al

SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19
Lize M. Grobbelaar, Chantelle Venter, Mare Vlok, Malebogo Ngoepe, Gert Jacobus Laubscher, Petrus Johannes Lourens, Janami Steenkamp, Douglas B. Kell and Etheresia Pretorius

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients.

Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet-poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin.

These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients.

This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.

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The study compared moderate to severe acute COVID patients with normal controls. Selected quotes.

They analysed with fluorescence microscopy, scanning electron microscopy, microfluidics, proteomics (liquid chromatography, mass spectroscopy)

 

This spike protein, that would presumbly be basically the same thing as we are injecting onto people as vaccines, to train the immune system to recognise covid 19?

Otherwise the vaccines wouldn't work?

 

Yes.

I think broadly speaking it doesn't matter what the origin of the spike protein is - it has the potential to cause trouble.

The spike protein as coded by mRNA vaccines is slightly modified (and protein subunit spike may also be modified) but I think that feature is unlikely to be of relevance to propensity for anomalous clot formation. However, even if we accept the above demonstration in vivo at scale, vaccine-derive S1 is in a controlled amount and (nominally) in upper arm soft tissues. Virus spike is uncontrolled in number and accompanied by S2 and other viral components and is far more likely to be systemic, rather than confined.

The risk/benefit is still strongly in favour of vaccine - though that is likely of academic comfort only to those affected. Still an unknown what the long-term effects of Omicron will be - but the default assumption should not be "mild acute in most / no long-term disease".