Impact of COVID-19 on platelet activity and the platelet releasate

Background : Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 100 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Several studies to date suggest a role for platelets in COVID-19-associated thrombosis. Aims : To assess the impact of COVID-19 on platelet activity and to characterise the proteome of the platelet releasate from COVID-19 patients, compared with healthy controls. Methods : Ethical approval was granted by the Institutional Review Board of the Mater Misericordiae University Hospital. Haematologic parameters of patients with severe COVID-19 disease (requiring intensive care;n = 34), with non-severe disease (not requiring intensive care;n = 20) and in general medical in-patients without COVID-19 ( n = 20) were assessed. Platelet function and activity were evaluated by secretion and platelet marker analysis ( n = 6 each cohort). The proteome of the platelet releasate was assessed using label-free mass spectrometry. Results : We demonstrated agonist-induced ADP release was 30-to-90 fold higher in COVID-19 patients compared with hospitalized controls (Fig. 1) and circulating levels of platelet-factor 4 (PF4), soluble P-selectin (sP-selectin) and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that COVID-19 patients possess hyperactive circulating platelets combined with a decreased activation threshold. Mass spectrometry analysis identified over 400 proteins from the releasate of COVID-19 patients and controls, including a multitude of inflammatory, vasoactive and vesicular proteins. The release of a subset of highly-relevant platelet proteins was modified based on the severity of COVID-19 infection. controls (Fig. 1) and circulating levels of platelet-factor 4 (PF4), soluble P-selectin (sP-selectin) and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that COVID-19 patients possess hyperactive circulating platelets combined with a decreased activation threshold. Mass spectrometry analysis identified over 400 proteins from the releasate of COVID-19 patients and controls, including a multitude of inflammatory, vasoactive and vesicular proteins. The release of a subset of highly-relevant platelet proteins was modified based on the severity of COVID-19 infection.