Complement-mediated extracellular vesicle release as a measure of endothelial dysfunction and prognostic marker for COVID-19 in peripheral blood - letter to the Editor

The recent articles in Clin. Hemorheol. Microcirc. by Jung et al. [1–3], elegantly highlighted the thrombotic complications that arise in severe coronavirus disease 2019 (COVID-19) and discussed the role vascular injury and associated hyper inflammation play in bringing about multi-organ failure in severe disease. Coagulation and venous thromboembolism (VTE) in COVID-19 commonly presents as deep vein thrombosis (DVT) or pulmonary embolism (PE), and occurs because of inflammation, blood vessel injury and associated endothelial dysfunction. Likely contributors to this thrombotic milieu, hitherto little discussed in this COVID-19 pandemic, include Extracellular Vesicles (EVs), nanosized, cell-derived intercellular communicative vesicles, carrying proteins, bioactive lipids and miRNAs. Endothelial cell- (EC-) derived EVs (EEVs) are often released because of endothelial injury [4] and also likely to contribute to this prothrombotic environment. Whilst EVs and VTE in cancer has been much described, there is a significant knowledge gap concerning EVs and VTE in infectious disease. This letter considers how, as part of ongoing inflammation, complement may be activated in SARS-CoV-2 infection and so mediate EV biogenesis. It also assesses the role procoagulant EVs play in the context of coagulopathy and VTE in COVID-19, and their potential as a prognostic peripheral blood marker