COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms

Thrombotic events that frequently occur in COVID-19 are predominantly venous thromboemboli (VTE) and are associated with increasing disease severity and worse clinical outcomes. Distinctive microvascular abnormalities in COVID-19 include endothelial inflammation, disruption of intercellular junctions and microthrombi formation. A distinct COVID-19-associated coagulopathy along with increased cytokines and activation of platelets, endothelium and complement occur in COVID-19, which is more frequent with worsening disease severity. This proinflammatory milieu may result in immunothrombosis, a host defence mechanism that can become dysregulated, leading to excess formation of immunologically mediated thrombi which predominantly affect the microvasculature. The haemostatic and immune systems are intricately linked, and multifactorial processes are likely to contribute to VTE and immunothrombosis in COVID-19. This state-of-the-art review will explore the pathobiological mechanisms of immunothrombosis and VTE in COVID-19 focusing on: COVID-19-associated coagulopathy, pathology, endothelial dysfunction and haemostasis, the immune system and thrombosis, genetic associations and additional thrombotic mechanisms. An understanding of the complex interplay between these processes is necessary for developing and assessing how new treatments affect VTE and immunothrombosis in COVID-19.

Automated summary

Thrombotic events in COVID-19, especially venous thromboemboli, are associated with disease severity and poor clinical outcomes. Distinctive microvascular abnormalities include endothelial inflammation, disruption of intercellular junctions, and microthrombi formation. COVID-19 can lead to immunothrombosis, and a better understanding of the pathobiological mechanisms is crucial for developing new treatments.