The role of the endothelium in SARS-CoV-2 infection and pathogenesis

Endothelial cell (EC) dysfunction is a characteristic complication of COVID-19. This review discusses the role of the endothelium during the pathogenesis of SARS-CoV-2, with a focus on different vascular beds, possible routes of infectivity and the impact of endothelial cell dysfunction across multiple organ systems. It is now known that COVID-19 disease elicits a distinct transcriptomic and molecular profile that is different to other viral infections, such as H1N1. Interestingly, there is also a suggested interplay between the heart and lungs that promotes the amplification of inflammatory cascades leading to an exacerbation in disease severity. Multiomic studies have informed common pathways that may be responsible for endothelial activation while also highlighting key differences in COVID-19 pathogenesis between organ systems. At a pathological level, endothelialitis is an endpoint result regardless of either a direct viral infection or via indirect effects independent of infection. Understanding if ECs are directly targeted by SARS-CoV-2 or are collaterally damaged amid a cytokine storm originating from other cells and organs can provide novel insights into disease progression and may highlight possible new therapeutic opportunities targeted at the damaged endothelium.