Background: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim of this study was to determine their functional and biochemical profile in patients with COVID-19 in dependence of mortality within 5-days after hospitalization. Methods: The COVID-19-related platelet phenotype was examined by analyzing their basal activation state via integrin αIIbβ3 activation using flow cytometry and the proteome by unbiased two-dimensional differential in-gel fluorescence electrophoresis. In total we monitored 98 surviving and 12 non-surviving COVID-19 patients over 5 days of hospital stay and compared them to healthy controls ( n = 12). Results: Over the observation period the level of basal αIIbβ3 activation on platelets from non-surviving COVID-19 patients decreased compared to survivors. In line with this finding, proteomic analysis revealed a decrease in the total amount of integrin αIIb (ITGA2B), a subunit of αIIbβ3, in COVID-19 patients compared to healthy controls; the decline was even more pronounced for the non-survivors. Consumption of the fibrin-stabilizing factor coagulation factor XIIIA (F13A1) was higher in platelets from COVID-19 patients and tended to be higher in non-survivors; plasma concentrations of the latter also differed significantly. Depending on COVID-19 disease status and mortality, increased amounts of annexin A5 (ANXA5), eukaryotic initiation factor 4A-I (EIF4A1), and transaldolase (TALDO1) were found in the platelet proteome and also correlated with the nasopharyngeal viral load. Dysregulation of these proteins may play a role for virus replication. ANXA5 has also been identified as an autoantigen of the antiphospholipid syndrome, which is common in COVID-19 patients. Finally, the levels of two different protein disulfide isomerases, P4HB and PDIA6, which support thrombosis, were increased in the platelets of COVID-19 patients. Conclusion: Platelets from COVID-19 patients showed significant changes in the activation phenotype, in the processing of the final coagulation factor F13A1 and the phospholipid-binding protein ANXA5 compared to healthy subjects. Additionally, these results demonstrate specific alterations in platelets during COVID-19, which are significantly linked to fatal outcome. Graphical Abstract
【저자키워드】 COVID-19, thrombosis, Platelets, Antiphospholipid syndrome, integrin αIIbβ3, coagulation factor XIII (FXIII, F13A1), annexin A5, eukaryotic initiation factor (EIF4A1), 【초록키워드】 coronavirus, Mortality, Hospitalization, Infection, outcome, flow cytometry, COVID-19 disease, Coagulation, Protein, Survivors, Platelet, phenotype, virus replication, proteome, severe pneumonia, autoantigen, proteomic, COVID-19 patients, Analysis, integrin, COVID-19 patient, Hospital stay, Support, plasma concentration, two-dimensional, Non-survivors, Consumption, acute respiratory syndrome, Activation, biochemical, subunit, healthy control, healthy subjects, alteration, syndrome, observation period, Final, pathogenesis of COVID-19, over, ITGA2B, consequence, decrease, nasopharyngeal viral load, significant changes in, examined, caused, significantly, functional, determine, correlated, eukaryotic, ANXA5, EIF4A1, F13A1, healthy controls;, P4HB, patients with COVID-19, PDIA6, TALDO1, 【제목키워드】 target, change, Annexin, Progressive, EIF4A1, F13A1, the SARS-CoV-2,