Alterations in platelet proteome signature and impaired platelet integrin α_IIbβ₃activation in patients with COVID-19

AbstractBackgroundPatients with coronavirus disease-19 (COVID-19) are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality.ObjectivesWe aimed to characterise the mechanism of altered platelet function in COVID-19 patients.MethodsThe platelet proteome, platelet functional responses and platelet-neutrophil aggregates were compared between patients hospitalised with COVID-19 and healthy control subjects using Tandem Mass Tag (TMT) proteomic analysis, Western blotting and flow cytometry.ResultsCOVID-19 patients showed a different profile of platelet protein expression (858 altered out of 5773 quantified). Levels of COVID-19 plasma markers were enhanced in COVID-19 platelets. Gene ontology (GO) pathway analysis demonstrated that levels of granule secretory proteins were raised, whereas some platelet activation proteins, such as the thrombopoietin receptor and PKCα, were lowered. Basally, COVID-19 platelets showed enhanced phosphatidylserine (PS) exposure, with unaltered integrin αIIbβ3activation and P-selectin expression. Agonist-stimulated integrin αIIbβ3activation and PS exposure, but not P-selectin expression, were significantly decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This interaction was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction.ConclusionsOverall, our data suggests the presence of two platelet populations in patients with COVID-19: one with circulating platelets with an altered proteome and reduced functional responses and another with P-selectin expressing neutrophil-associated platelets. Platelet driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients.Essentials-COVID-19 patient platelet function and platelet proteins were compared with healthy controls-Proteomic analysis of platelets indicated that COVID-19 decreased platelet activation proteins-Agonist induced PS exposure and integrin αIIbβ3activation were impaired in COVID-19-COVID-19 led to maximal levels of P-selectin dependent platelet-neutrophil aggregates