Platelets and neutrophil extracellular traps (NETS) in immunothrombosis progression at COVID-19

Background : Virus infection COVID-19 caused by beta-coronavirus SARS-CoV-2 spread over the majority of countries and continents within several months. Pathophysiology of the disease is directly connected to uncontrollable progression of system inflammation, resulting in developed immunothrombosis of microvasculature and multiple organ dysfunction. Aims : In the present investigation, the effort was made to to clarify several pathophysiological mechanism of COVID-19 development, to determine diagnostic and prognostic criteria of disease severity and outcome. Methods : The blood of 87 patients with COVID-19 was examined using routine hemostasiological tests. In parallel, morphological and functional features of living functioning platelets were evaluated using quantitative phase imaging (QPI) technology at the level of superresolution and 3D visualization of cells and subcellular structures. According to the author ' s technique, the formation of neutrophil extracellular traps during netosis (NETosis) of neutrophils was analyzed in whole blood smears. Results : It was found that patients are characterized by the development of COVID-associated coagulopathy, which correlates with the severity of the disease. We found that, compared with control, the patients had a elevated plasma D-dimer, fibrinogen and FDPs, as well as shortened TT. We identified the increasing by 27% platelets with low and high level of activation (64 ± 6.9% vs 37% in norm) in 83% of patients. The level of NETs was statistically significantly (53.1 ± 7.2%, P < 0.05) higher than healthy volunteers (9.3 ± 3.5%) and progressively increased with the development of acute respiratory distress syndrome. Conclusions : Hemostatic disorders during SARS-CoV-2 infection can be caused by hyperactivity of platelets, hypercoagulation, hyperfibrinolysis and an inadequate immune response due to the formation NETs, finally causing coronavirus-induced coagulopathy. Platelets and neutrophils not only serve as markers of acute infection, but also, as a source of neutrophilic extracellular traps, play a key role in the development of immunothrombosis, which ultimately leads to acute respiratory failure with COVID-19.