New research shows long-COVID-19 microclotting and inflammatory molecule abnormalities.

Introduction
Many survivors have ongoing symptoms months after the virus infection resolves. Long Covid is COVID-19 post-acute sequelae (PASC).

SARS-CoV-2 persistence, hyperactivation of platelets and microclots, autoantibody production, dysregulated immunity, multi-organ dysfunction, and reactivation from dormancy are six reasons causing persistent COVID symptoms.

A medRxiv* study examines how endothelial activation and inflammation cause PASC microclots.

Platelets and fibrinaloid microclots
Long-Covid patients have circulated microclots. SARS-CoV-2 spike protein plasma activation can cause fibrin amyloid microclots that defy fibrinolysis.

These microclots contain inflammatory substances such alpha 2-antiplasmin (α2AP), fibrinogen chains, von Willebrand factor (vWF), platelet factor 4 (PF4), serum amyloid A (SAA), and antibodies. Acute severe COVID-19 causes coagulopathy.

Without fixing this, tissue damage from toxic hypoxia and inadequate oxygen exchange may remain. For up to 49 weeks after acute infection, clots and other vascular events were higher than expected.

A failing fibrinolytic system and prolonged coagulopathy produce extensive endothelial inflammation, according to published studies.

Study details
This study finds indicators in the soluble fraction of blood that may validate the significance of endothelial disease and coagulopathy in protracted COVID.

vWF, PF4, SAA, and α-2AP were chosen from previous studies of microclot-trapped biomarkers. E-selectin and PECAM-1, endothelial damage indicators, were also examined.

Endothelial activation or aberrant coagulation pathway activation releases these substances. Some, like α-2AP, inhibit fibrinolysis, allowing microvascular thrombosis surrounding aberrant clots and increasing thromboembolism risk. This molecule predicts poor cardiovascular disease outcomes.

Endothelial dysfunction is crucial to protracted COVID, hence its indicators were chosen. In addition to investigating for increases in these chemicals in extended COVID, the investigators evaluated their role in protein-protein interactions with plasma proteins to produce microclot formation and platelet receptors to hyperactivate platelets.

The study found…
Long-term COVID patients had greater mean levels of all six compounds, confirming previous findings.

Long-term COVID patients had higher mean levels of α-2AP and the other five molecules than controls. Researchers expect far greater levels.

This is worrying because a large number of these inflammatory chemicals has previously been demonstrated to be imprisoned inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules).

These chemicals cause inflammation, platelet activation, endothelial damage, and severe vascular injury. This study showed that long-term COVID patients had higher plasma soluble concentrations.

Coagulation involves the six markers. vWF activates and aggregates intravascular platelets, causing fibrinogen binding and thrombosis. SAA also binds to extracellular matrix molecules and endothelium TLRs, releasing inflammatory mediators and reactive oxygen species (ROS).

Endothelium damage causes functional impairment and early atheroma. The NLRP3 inflammasome initiates the coagulation cascade, producing thrombin.

Systemic inflammatory molecule concentration in controls and Long COVID. (A) SAA-(*p<0.05), (B) α2AP-(**p<0.01), (C) PF4-(*p<0.05), and (D) VWF concentrations in controls and Long COVID using PPP (*p<0.05). E-selectin-and**p<0.01. Controls and Long COVID serum PECAM-1 concentrations (*p<0.05). Abbreviations: PF4: Platelet factor 4, VWF: Von Willebrand Factor, E-selectin: endothelium-leukocyte adhesion molecule 1, PECAM-1: Platelet endothelial cell adhesion molecule-1, PPP: Platelet poor plasma.

Systemic inflammatory molecule concentration in controls and Long COVID. (A) SAA-(*p<0.05), (B) α2AP-(**p<0.01), (C) PF4-(*p<0.05), and (D) VWF concentrations in controls and Long COVID using PPP (*p<0.05). E-selectin-and**p<0.01. Controls and Long COVID serum PECAM-1 concentrations (*p<0.05). Abbreviations: PF4: Platelet factor 4, VWF: Von Willebrand Factor, E-selectin: endothelium-leukocyte adhesion molecule 1, PECAM-1: Platelet endothelial cell adhesion molecule-1, PPP: Platelet poor plasma.

By binding to plasmin, microclots resist fibrinolysis. This causes embolism, ischemic stroke, and artery and vein clots.

E-selectin increases confirm endothelial activation. This chemical allows white blood cells to roll on active endothelium and cause platelet-endothelium adhesion.

E-selectin and PECAM-1 caused microclots and platelet hyperactivation in healthy blood samples, as they did in long-term COVID patients. Plasma protein misfolding and platelet receptor hyperactivation may trigger these occurrences.

Conclusions
Long COVID results from fibrinolysis-resistant fibrin-amyloid microclots causing impaired coagulation and ischemia-reperfusion damage. Such clots and higher levels of six inflammatory mediators involved in coagulation and endothelial activation corroborate this.

The common pathogenic process is thrombotic endotheliitis, which includes aberrant fibrinaloid microclots, hyperactivated platelets, endotheliitis, and increased prothrombotic inflammatory chemicals that interact with each other, platelets, and the endothelium.

 

READ MORE

Important

*MedRxiv provides preliminary scientific studies that are not peer-reviewed and should not be used to guide clinical treatment or health-related behaviour.

Journal reference:

Leave a Reply

error: Content is protected !!
Open chat
WhatsApp Now