COVID-19 Is an Endothelial Disease: Implications of Nitric Oxide

Endothelial cells are a clinically important infection site for COVID-19, both as a mechanism for disease pathogenesis and as a therapeutic target. People with dysfunctional endothelium, defined by nitric oxide deficiency, appear to have a more severe disease course. As such, nitric oxide has therapeutic potential to mitigate COVID-19 severity. Inhaled nitric oxide appears to improve outcomes, although this strategy neglects systemic endothelium. Meanwhile, early studies have documented that endothelial protective medications, such as the administration of statins and ACE-inhibitors, are associated with less severe disease and reduced mortality. Importantly, these medications augment endothelial sources of nitric oxide, which may explain this effect.