Abstract
Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet–leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.
Highlights
Despite severe acute respiratory syndrome coronavirus2 (SARS-CoV-2)’s worldwide spread, little is known about the pathophysiological mechanisms leading to multiorgan hypercoagulable state with increased incidence of cardiovascular complications and venous thrombotic events has been reported in several studies[1,2,3,4,5,6,7]
We investigated the expression of platelet transmembrane receptors and adhesion molecules at baseline level and after in vitro platelet stimulation in hospitalized COVID-19 patients without pre-existing conditions and in healthy donors using mass cytometry by time of flight (CyTOF)
Upon thrombin receptor-activating peptide (TRAP) stimulation, mass cytometry detected a significantly higher expression of the platelet activation marker Pselectin in samples of COVID-19 patients compared to healthy controls (p = 0.0176), but LAMP-3 did not show significant differences (p = 0.40, Fig. 3a)
Summary
2 (SARS-CoV-2)’s worldwide spread, little is known about the pathophysiological mechanisms leading to multiorgan hypercoagulable state with increased incidence of cardiovascular complications and venous thrombotic events has been reported in several studies[1,2,3,4,5,6,7]. Two studies reported in COVID-19 alterations in platelet transcriptome and proteome, and an increased platelet reactivity[11,12]. A recent study described the presence microvascular thrombi in lung, heart and kidney containing neutrophil extracellular traps (NETs) in severe. SARS-CoV-2 infection, as well as circulant neutrophilplatelet aggregates and immunothrombotic dysregulation, Official journal of the Cell Death Differentiation Association. Bongiovanni et al Cell Death and Disease (2021)12:50 which changes with disease severity[13]. The role of platelet activation and changes of transmembrane receptor expression in COVID-19-induced coagulopathy still needs to be further investigated
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