Two papers recently published on EBioMedicine confirm that the excessive NET formation drives immunopathology in severe COVID-19 associated disseminated pulmonary intravascular coagulopathy.

Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.

Here, it’s shown that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs.

In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage. These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.

In the commentary entitled “Immunothrombosis in severe COVID-19”, Daigo Nakazawaa and Akihiro Ishizub support the idea that the prevention of excessive NET formation and aggregation could provide an approach to
inhibit vascular occlusion and the development of severe COVID-19.

For this purpose, dexamethasone (a cell aggregation inhibitor) and
PAD inhibitors (inhibitors of NET formation) may be considered.
Heparin accelerates NET degradation by DNase I. Moreover, previous studies have demonstrated that heparin can dismantle NETs and neutralize NETderived histones, which are detrimental factors of NETs.
Although further studies are needed, this classical anticoagulant is a
promising resource against severe COVID-19.