COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury

Nicosia, Roberto F.; Ligresti, Giovanni; Caporarello, Nunzia; Akilesh, Shreeram; Ribatti, Domenico

COVID-19 patients who are critically ill develop vascular complications characterized by thrombosis of small, medium and large vessels. Dysfunction of the vascular endothelium due to the SARS-CoV-2 infection has been implicated in the pathogenesis of the COVID-19 vasculopathy. Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express ACE2 – the receptor that SARS-CoV-2 uses to gain entry into cells – or express it at low levels and are resistant to the infection. These new findings, together with the observation that COVID-19 triggers a cytokine storm capable of injuring the endothelium and disrupting its antithrombogenic properties, favor an indirect mechanism of endothelial injury mediated, locally, by an augmented inflammatory reaction to infected nonendothelial cells such as the bronchial and alveolar epithelium and, systemically, by the excessive immune response to infection. Here we review the vascular pathology of COVID-19 and critically discuss the potential mechanisms of endothelial injury in this disease.