Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients

•The cytokine storm present in COVID-19 patients induces, together with the imbalance of endothelial functions, a massive cell activation with production of tissue factor, mainly by platelets, granulocytes, and MVs.•Plasma MV-associated thrombin generation is present in patients despite prophylactic anticoagulation.•COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to what is observed in vivo. This effect is blunted by pre-incubation with tocilizumab, giving insights into the IL-6–mediated platelet activation that triggers the hypercoagulable state in COVID-19, suggesting the potential effectiveness of anti–IL-6 antibodies and antiplatelet drugs.•Our data provide the bench-to-clinic rationale behind the ongoing clinical trial assessing the potential effectiveness of antiplatelet drugs and IL-6R antagonists in the treatment of COVID-19 patients.