AUTHOR=Ercan Huriye , Schrottmaier Waltraud Cornelia , Pirabe Anita , Schmuckenschlager Anna , Pereyra David , Santol Jonas , Pawelka Erich , Traugott Marianna T. , Schörgenhofer Christian , Seitz Tamara , Karolyi Mario , Yang Jae-Won , Jilma Bernd , Zoufaly Alexander , Assinger Alice , Zellner Maria 

TITLE=Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.779073

DOI=10.3389/fcvm.2021.779073

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 12).</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p>