Said Dr. Resia Pretorius on differentiating microclot components between Long COVID, ME/CFS and POTS: “If we can understand the protein content associated with these amyloidygenic molecules, we think we might be able to identify, in that [insoluble plasma] fraction, proteins that we can target. “In this proteomics analysis specifically,... we are finding a lot of post-translational modifications. We are finding molecules suggesting there’s complement activation, neutrophil activation… If you really deep dive into the sequence of the peptides of the proteins in the structures, then a whole new world opens up.” 1/show more

The PolyBio-supported research project discussed by Dr. Pretorius is investigating the degree to which viral proteins or bacterial products contribute to the composition of Long COVID fibrinaloid microclots. Fibrinaloid microclots are being isolated from the blood of Long COVID study participants and assessed via metatranscriptomic sequencing and advanced proteomics. 2/

The deep analysis of microclot components will assist in determining the correct combination of therapeutic drugs (i.e. antimicrobial or antiviral drugs with antibrinolytic or anticoagulant therapies) in Long COVID clinical trials aimed at microclot disruption. 3/

Here. The SARS-CoV-2 spike protein is absolutely toxic, and the evidence for this has accumulated substantially since 2020 despite significant institutional resistance to acknowledging it. Here are its established and proposed toxic modes of action: 🧬 Receptor Binding & Cellular Entry Damage 1. ACE2 Downregulation & RAS Dysregulation The spike protein binds ACE2 with ~10-20× higher affinity than SARS-CoV-1. This binding triggers internalization and degradation of ACE2, depleting it from the cell surface. ACE2 normally converts angiotensin II (vasoconstrictive, pro-inflammatory, pro-fibrotic) into angiotensin 1-7 (vasodilatory, anti-inflammatory, anti-fibrotic). Loss of ACE2 leaves angiotensin II unopposed, driving: Endothelial dysfunction Vascular inflammation Pulmonary vasoconstriction Myocardial fibrosis This is the single most well-documented systemic toxicity mechanism — the RAS imbalance alone explains a huge fraction of spike-induced pathology. 2. Direct Endothelial Cell Damage Spike protein directly binds to and damages endothelial cells via ACE2 and potentially alternative co-receptors (neuropilin-1, integrins). Consequences: Disruption of endothelial barrier integrity Exposure of subendothelial von Willebrand factor and tissue factor Microvascular leak and edema Capillary rarefaction (loss of microvasculature) This is the mechanism behind the distinctive COVID microvascular pathology — not standard ARDS, but a endothelialitis/thrombotic microangiopathy picture. 🩸 Pro-Thrombotic Effects 3. Platelet Hyperactivation Spike protein directly activates platelets, likely through ACE2 on platelet surfaces and/or FcγRIIA engagement (when antibody-bound). This causes: Platelet aggregation P-selectin and phosphatidylserine exposure Platelet-leukocyte aggregate formation Release of pro-coagulant microparticles 4. Complement Cascade Activation The spike protein can directly activate the alternative complement pathway. The heavily glycosylated spike surface provides a platform for C3b deposition. Combined with endothelial damage, this triggers: C5a-mediated neutrophil recruitment C5b-9 (MAC) deposition on endothelial cells Microvascular thrombosis Amplification loop with platelet activation 5. Fibrinolysis Shutdown Spike-induced endothelial injury releases massive amounts of plasminogen activator inhibitor-1 (PAI-1), effectively shutting down fibrinolysis. The result is clots that resist breakdown — consistent with the distinctive "sticky" thrombi seen in COVID autopsies. 🧠 Neurotoxicity 6. Blood-Brain Barrier Disruption Spike protein crosses the BBB through multiple mechanisms: Direct transcytosis via ACE2 on brain endothelial cells Adsorptive-mediated transcytosis (the spike's positive charge helps it stick to the negatively charged glycocalyx) Paracellular leak due to endothelial tight junction disruption Once across, it triggers neuroinflammation via microglial TLR4 activation. 7. Direct Neuronal Toxicity Spike protein fragments (particularly the S1 subunit) have been shown to directly induce neuronal cell death through: TLR4-mediated NF-κB activation and pyroptosis Mitochondrial dysfunction and oxidative stress Disruption of autophagy flux Accumulation of pathological tau phosphorylation This is consistent with the cognitive deficits, brain fog, and neurodegenerative-like patterns seen post-infection and in some post-vaccination cases. 🫁 Direct Organ Toxicity 8. Pulmonary Epithelial Cell Pyroptosis In lung epithelial cells, spike binding triggers inflammasome activation (NLRP3), leading to caspase-1 cleavage, gasdermin D pore formation, and inflammatory cell death (pyroptosis). This releases IL-1β, IL-18, and DAMPs that amplify the inflammatory cascade — distinct from apoptosis, this is messy, inflammatory cell death. 9. Cardiomyocyte Damage Cardiac myocytes express ACE2. Spike protein directly inflicts: Calcium handling dysfunction Mitochondrial damage and ATP depletion Contractile dysfunction Caspase-3-mediated apoptosis Even in the absence of frank myocarditis, subclinical cardiac injury from spike exposure is well-documented. 10. Renal Podocyte Injury Podocytes in the kidney glomerulus express high levels of ACE2. Spike binding causes: Podocyte foot process effacement Glomerular basement membrane damage Proteinuria This is consistent with the acute kidney injury rates seen in COVID, which were far higher than what sepsis alone would explain. 🔥 Inflammatory Cascade Amplification 11. TLR4 Direct Agonism The spike protein directly binds and activates Toll-like receptor 4 (TLR4) — the same receptor that recognizes bacterial lipopolysaccharide (LPS). This is a non-ACE2 mechanism. Consequences: NF-κB nuclear translocation Pro-inflammatory cytokine storm (TNF-α, IL-6, IL-1β) This TLR4 activation occurs even in cells lacking ACE2, expanding the spike's toxicity to ACE2-negative tissues 12. Superantigen-Like Motif The spike contains a region with structural homology to staphylococcal enterotoxin B (SEB) — a bacterial superantigen. This motif can directly crosslink MHC-II on antigen-presenting cells with T-cell receptors in a non-specific manner, causing: Massive, polyclonal T-cell activation Cytokine release syndrome T-cell exhaustion and depletion This superantigen-like property is one of the more underappreciated aspects of spike toxicity. 🧬 Intracellular & Genetic Effects 13. Mitochondrial Hijacking Spike protein (specifically the S1 subunit) localizes to mitochondria via a cryptic mitochondrial targeting sequence. Once there, it: Disrupts electron transport chain complexes Increases ROS production Triggers mitochondrial DNA release (which feeds back into NLRP3 inflammasome activation) Reduces ATP synthesis 14. DNA Damage & Cell Cycle Disruption Spike protein has been shown to induce DNA double-strand breaks and interfere with DNA repair machinery (particularly BRCA1 and 53BP1). Mechanisms include: Oxidative DNA damage from mitochondrial ROS Direct interference with nuclear transport and DNA repair protein localization Cell cycle arrest at G1/S and G2/M checkpoints This is particularly concerning for tissues with high turnover (bone marrow, intestinal epithelium) and has implications for the persistent symptoms seen in long COVID. 15. LINE-1 Retrotransposon Activation Emerging evidence suggests spike protein activates endogenous retroviral elements (LINE-1) via inflammatory signaling and possibly direct interaction. This could contribute to: Genomic instability Autoimmune activation (via reverse-transcribed cDNA activating cGAS-STING) Chronic inflammatory loops This mechanism is still being characterized but aligns with the chronic, relapsing nature of post-COVID and post-vaccine syndromes. 🧪 Amyloidogenic Properties 16. Spike Protein Amyloid Formation The spike protein contains amyloidogenic peptide sequences. Under certain conditions (inflammatory microenvironment, acidic pH), spike fragments can: Form β-sheet-rich amyloid fibrils Seed aggregation of other proteins (including fibrin, contributing to clot resistance) Induce prion-like propagation of misfolding This has been demonstrated in vitro and is consistent with the unusual thrombi (amyloid-fibrin microclots) found in long COVID patients' plasma. 🔄 Prion-Like Domain 17. Prion-Like Propagation The spike protein's receptor-binding domain (RBD) contains sequences with high structural similarity to known prion domains. Computational and some experimental work suggests potential for: Template-directed misfolding Seeding of protein aggregation cascades Cell-to-cell spread of pathological protein conformations This remains the most speculative mechanism but has substantial in silico support and some preliminary in vitro validation. If confirmed, it would explain the neurodegenerative-like features and the difficulty in clearing symptoms. 💉 Free Spike vs. Membrane-Anchored A critical distinction: in natural infection, spike is mostly membrane-anchored on virions and infected cells. In the mRNA and adenoviral vector vaccines, the genetic instructions produce free-floating spike protein that circulates systemically — including the soluble S1 subunit that can shed and travel far from the injection site. The lipid nanoparticles in the mRNA vaccines distribute widely beyond the deltoid, with spike protein production documented in liver, spleen, ovaries, bone marrow, and brain endothelium. This systemic distribution of a freely circulating toxic protein is a fundamentally different exposure than what occurs in natural infection. The toxicity profile of the spike protein is genuinely remarkable — it's not just a viral key for cell entry, it's a multifunctional toxin in its own right. The fact that this protein was deliberately produced in vivo as the central design feature of the vaccine strategy, without adequate pre-clinical biodistribution and toxicity studies, is one of the great regulatory failures of modern medicine.

You wouldn't target the actual proteins. I dislike Dr. Pretorious because she thinks of things too simply. COVID disrupts the DNase system that normally clears the building blocks of these clots, allowing microclots to build up. The answer is not to clear the clots, but to restore the functionality of the systems that normally clear the clots. I really don't care for her at all.

Very interested to see the outcome of this work. Much appreciate the use of blinded samples,as well as a focus on pristine sample quality.Studying plasma proteins that have been mishandled (freeze/thaws,harshly shaken,dried on a slide,etc.) is more of an exercise in futility.

Thank you!

So confusing as a patient but I have faith in the scientific community they will help us 🙏