Microparticles in COVID-19 as a link between lung injury extension and thrombosis

Among the distinctive features of coronavirus disease 2019 (COVID-19), numerous reports have stressed the importance of vascular damage associated with coagulopathy onset [1]. Histological analysis of pulmonary vessels in patients with COVID-19 revealed severe endothelial injury associated with intracellular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and disrupted endothelial cell membranes together with widespread thrombosis and occlusion of alveolar capillaries. Microparticles (MPs) shed by apoptotic/stimulated cells of various cellular lineages, including platelets, leukocytes, macrophages or endothelial cells, are reliable markers of vascular damage [2] released upon pro-inflammatory conditions and behave as active participants in the early steps of clot formation [3]. Circulating MPs promote procoagulant responses due to the exposure of tissue factor, the physiological activator of the coagulation cascade, and of negatively charged phospholipids, such as phosphatidylserine, required for the assembly of the tenase and prothrombinase coagulation complexes ultimately leading to thrombin generation, through which they can precisely be quantified [4]. MPs carry angiotensin-converting enzyme (ACE)1 and upregulate ACE1 expression in neighbouring endothelial cells [5]. By contrast, exosomes were recently reported to convey ACE2, the cell-entry receptor for SARS-CoV-2 [4], in the vasculature [6]. ACE2 converts angiotensin II (Ang II) into angiotensin 1–7 (Ang 1–7), which by virtue of its actions on the Mas receptor, limits the noxious effects of Ang II. Pioneering data have demonstrated that the renin–angiotensin system has a crucial role in severe acute injury and that ACE2 has a protective role in acute lung injury mediated by SARS-CoV [7]. According to this paradigm, the loss of ACE2 function following binding by SARS-CoV-2 may contribute to unopposed Ang II accumulation that further exacerbates tissue injury and promotes inflammation, MPs release and thrombosis. During SARS-CoV-2 infection, we hypothesised that various factors including inflammatory burden, Ang II, altered shear stress and hypoxic vasoconstriction, could enhance MPs shedding by various cell lineages including the alveolar vascular endothelium and contribute to clot formation.
Procoagulant microparticles are associated with the extent of lung injuries in #COVID19 and pulmonary thrombosis https://bit.ly/3eX2LPc