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
Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Division of Visceral Surgery, Department of General Surgery, General Hospital Vienna, Medical University of Vienna, Vienna, Austria.
Front Cardiovasc Med. 2021 Nov 11;8:779073. doi: 10.3389/fcvm.2021.779073. eCollection 2021.
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. 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 ( = 12). 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. 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.
严重急性呼吸综合征冠状病毒2感染的致命后果不仅由严重肺炎引起，还由血栓形成导致。血小板是血栓形成的重要调节因子，但其在新型冠状病毒肺炎（COVID-19）发病机制中的作用尚不清楚。本研究的目的是确定COVID-19患者血小板的功能和生化特征与住院后5天内死亡率的关系。通过流式细胞术分析整合素αIIbβ3激活状态来检测COVID-19相关血小板表型，并通过无偏差二维差异凝胶荧光电泳分析蛋白质组。我们总共监测了98名存活的和12名非存活的COVID-19患者，观察其住院5天期间的情况，并将他们与健康对照者（n = 12）进行比较。在观察期内，与存活患者相比，非存活COVID-19患者血小板上基础αIIbβ3激活水平降低。与此发现一致，蛋白质组学分析显示，与健康对照者相比，COVID-19患者中αIIbβ3的一个亚基整合素αIIb（ITGA2B）总量减少；非存活者的下降更为明显。COVID-19患者血小板中纤维蛋白稳定因子凝血因子XIIIA（F13A1）的消耗更高，非存活者中往往更高；后者的血浆浓度也有显著差异。根据COVID-19疾病状态和死亡率，在血小板蛋白质组中发现膜联蛋白A5（ANXA5）、真核起始因子4A-I（EIF4A1）和转醛醇酶（TALDO1）的含量增加，且与鼻咽病毒载量相关。这些蛋白质的失调可能在病毒复制中起作用。ANXA5也被确定为抗磷脂综合征的自身抗原，这在COVID-19患者中很常见。最后，支持血栓形成的两种不同的蛋白质二硫键异构酶P4HB和PDIA6在COVID-19患者血小板中的水平升高。与健康受试者相比，COVID-19患者的血小板在激活表型、最终凝血因子F13A1的加工过程以及磷脂结合蛋白ANXA5方面表现出显著变化。此外，这些结果表明COVID-19期间血小板存在特定改变，这些改变与致命结局显著相关。
