Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review.

Coronavirus disease 2019 (COVID-19) causes acute microvascular thrombosis in both venous and arterial structures which is highly associated with increased mortality. The mechanisms leading to thromboembolism are still under investigation. Current evidence suggests that excessive complement activation with severe amplification of the inflammatory response (cytokine storm) hastens disease progression and initiates complement-dependent cytotoxic tissue damage with resultant prothrombotic complications. The concept of thromboinflammation, involving overt inflammation and activation of the coagulation cascade causing thrombotic microangiopathy and end-organ damage, has emerged as one of the core components of COVID-19 pathogenesis. The complement system is a major mediator of the innate immune response and inflammation and thus an appealing treatment target. In this review, we discuss the role of complement in the development of thrombotic microangiopathy and summarize the current data on complement inhibitors as COVID-19 therapeutics.