Fig. 1

Molecular mechanisms involved in the acute inflammation and coagulation abnormalities of COVID-19. a The SARS-CoV-2 infection triggers an inflammatory cellular infiltrate in the alveolar lumen releases toxic molecules by macrophages and neutrophils, such as IL-1β, IL-8, IL-6 and TNF-α. The cytokines storm lead to diffuse alveolar damage, pulmonary oedema. b The damage and /or activation of blood vessels endothelium by viral infection and pro-inflammatory cytokines respectively induce platelet and monocyte aggregation in the vascular wall. These events are accompanied by increased expression of the tissue factor (TF) leading to activation of extrinsic pathway coagulation cascade culminating with the thrombi formation. Moreover, the thrombotic microangiopathy, may also be consequence of uncleaved large multimers of VWF, due to a decrease in the plasma levels of ADAMTS13. c Finally, as consequence of blood vessels endothelium viral infection, ACE2 is internalized, and sheddase activity of ADAM17 is increased. The ACE2 downmodulation and TNF-α and IL-6R release exacerbates the imbalance of RAS, leading to increase inflammation. The virus-mediated PtdSer exposure on the outer leaflet of the cell membrane emerge as an underlying mechanism to activate TF and extrinsic pathway coagulation cascade and inflammation (not shown)