The role of the endothelium in long COVID.

SARS-CoV2 infection significantly increases the risk of cardiovascular events through multiple interconnected mechanisms including systemic inflammation, dysautonomia, endothelial dysfunction, and prothrombotic states. The endothelium plays a critical role in this increase in risk together with dysautonomia and mast cell activation. SARS-CoV2 activates endothelial cells creating a pro-inflammatory, and pro-thrombotic phenotype. This phenotype could lead to microcirculatory changes that decrease oxygen delivery to tissues because of loss of laminar flow, lack of nitric oxide dependent vasodilation, increased viscosity and abnormal constriction of vascular smooth muscle cells due to neuropathy. There are several ways of identifying patients with endothelial dysfunction and the most used is flow mediated dilation. Many randomized trials have already found significant treatments for endothelial dysfunction and include antihypertensives, statins, beta-blockers, supplements and lifestyle interventions. Only two studies using vitamin C and L-arginine demonstrated improvements in flow mediated dilation in patients with long COVID.