Platelet-leukocyte crosstalk in COVID-19: How might the reciprocal links between thrombotic events and inflammatory state affect treatment strategies and disease prognosis?

Platelet-leukocyte crosstalk is commonly manifested by reciprocal links between thrombosis and inflammation. Platelet thrombus acts as a reactive matrix that recruits leukocytes to the injury site where their massive accumulation, activation and migration promote thrombotic events while triggering inflammatory responses. As a life-threatening condition with the associations between inflammation and thrombosis, COVID-19 presents diffuse alveolar damage due to exaggerated macrophage activity and cytokine storms. These events, together with direct intracellular virus invasion lead to pulmonary vascular endothelialitis, cell membranes disruption, severe endothelial injury, and thrombosis. The developing pre-alveolar thrombus provides a hyper-reactive milieu that recruits circulating leukocytes to the injury site where their activation contributes to thrombus stabilization and thrombosis propagation, primarily through the formation of Neutrophil extracellular trap (NET). NET fragments can also circulate and deposit in further distance where they may disseminate intravascular thrombosis in severe cases of disease. Thrombi may also facilitate leukocytes migration into alveoli where their accumulation and activation exacerbate cytokine storms and tissue damage, further complicating the disease. Based on these mechanisms, whether an effective anti-inflammatory protocol can prevent thrombotic events, or on the other hand; efficient antiplatelet or anticoagulant regimens may be associated with reduced cytokine storms and tissue damage, is now of interests for several ongoing researches. Thus shedding more light on platelet-leukocyte crosstalk, the review presented here discusses the detailed mechanisms by which platelets may contribute to the pathogenesis of COVID-19, especially in severe cases where their interaction with leukocytes can intensify both inflammatory state and thrombosis in a reciprocal manner. • Mutual interactions between platelets and leukocytes promote both thrombosis and inflammatory responses. • As the serious inflammatory condition, COVID-19 may also be associated with thrombotic events due to vascular inflammation or injury. • Direct and indirect vascular damage may occur due to virus invasion or leucocyte-dependent cytotoxic effect respectively. • Endothelialitis caused by cytokine storms may lead to vascular lesion and thrombosis in pre-alveolar vessels. • Pre-alveolar thrombi facilitate the migration of activated leucocyte, gating the sources of cytolytic and inflammatory agents in to the site of infection. • Therefore thrombosis may intensify the disease condition by the enhancements of cytokine storms and pulmonary damage. • Some clinical trials have shown evidence of reciprocal treatment of thrombosis and inflammation in COVID-19. • Exploring the direct cross-talk between inflammatory and thrombotic events sheds more light on the pathogenesis and treatment approaches of COVID-19. [ABSTRACT FROM AUTHOR]