Immunothrombosis in severe COVID-19: A Lancet study
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Recent studies have revealed that coagulation disorders and thrombotic events contribute to high mortality in COVID-19. It has been demonstrated that SARS-CoV-2 infection induces vascular endothelial injury, resulting from coagulation. However, the pathological feature of thrombus induced by SARS-CoV-2 remains incompletely understood.

Researchers demonstrated that, in severe COVID-19 patients, neutrophils were increased in the blood, exhibiting a so-called low-density phenotype, were strongly activated, and decorated with platelets. In addition, several serum or plasma markers, such as D-dimers, cell-free DNA, myeloperoxidase (MPO)- and neutrophil elastase (NE)-DNA complexes, and citrullinated histone H3 (citH3), were elevated in severe COVID-19 patients.

Because these are degradation products of fibrin or neutrophil extracellular traps (NETs), an enhanced turnover of coagulation and NET formation appears to characterize severe COVID-19. Correspondingly, aggregated NETs were detected in the clots that occluded microvessels in the lungs and other organs of COVID-19 patients obtained by autopsy.

The mechanism of NET induction by SARS-CoV-2 is debatable. Neutrophils themselves do not express ACE2, the receptor for SARS-CoV-2. In contrast, vascular endothelial cells provide abundant ACE2 for SARS-CoV-2 next to alveolar epithelial cells in the lungs. Based on the loss of CD31+ cells in the endothelium that were close to the aggregated NETs, Researchers suggested that the injury of vascular endothelial cells infected with SARS-CoV-2 could trigger neutrophil attraction and NET formation. This is consistent with the concept of immunothrombosis. However, another pathway via virus-mediated ROS production may also be involved in NET formation after SARS-CoV-2 infection.

Researchers suggested that the prevention of excessive NET formation and aggregation could provide an approach to inhibit vascular occlusion and the development of severe COVID-19. In a study, heparin accelerated NET degradation by DNase I. Moreover, previous studies have demonstrated that heparin can dismantle NETs and neutralize NET-derived histones, which are detrimental factors of NETs. Although further studies are needed, this classical anticoagulant is a promising resource against severe COVID-19.

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