Ricerc@Sapienza

Patients with Coronavirus-associated disease 2019 (COVID-19) display alterations of the hemostatic system and the presence of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet activity, aggregation and agglutination remains to be clarified. It is also not known how microRNAs influence platelet functions in these patients. In the present proposal, we will measure total levels of von Willebrand factor (vWF) and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the intensive care unit of Policlinico Umberto I university hospital. Moreover, we will evaluate platelet aggregation in response to agonists, (ADP, collagen, arachidonic acid) and platelet agglutination in response to ristocetin (RCo). We will investigate whether the levels of vWF antigen and the active form of vWF binding to platelets (vWF:RCo), are altered in these patients. We will analyze if this is associated with higher agglutination rates induced by RCo, thereby indicating an increased capability of vWF to bound to platelets. Conversely, we will investigate if platelet aggregation in response to both ADP and collagen is different in COVID-19 patients.
This study will help in understanding if COVID-19 is associated with increased vWF-induced platelet agglutination and reduced platelet responsiveness to aggregation stimuli. Furthermore, we will establish complete miRNome profile and identify platelet miRNAs correlated with activation and aggregation functions from plasma of Covid-19 patients. Further, we will analyze platelets from Covid-19 patients for their miRNA content to identify if disease causing miRNAs use platelets as vehicles. The results obtained from this proposal will have translational relevance since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic strategies in COVID-19 patients.