Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19.
Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19.
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DOI：
10.1161/circresaha.120.317703
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发表时间：
2020-09-17
影响因子：
20.1
通讯作者：
Boilard E
中科院分区：
文献类型：
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作者：
Zaid Y;Puhm F;Allaeys I;Naya A;Oudghiri M;Khalki L;Limami Y;Zaid N;Sadki K;Ben El Haj R;Mahir W;Belayachi L;Belefquih B;Benouda A;Cheikh A;Langlois MA;Cherrah Y;Flamand L;Guessous F;Boilard E
文本中提供了补充数字内容。除了在2019冠状病毒病（COVID-19）中普遍存在的压倒性肺部炎症外，高凝状态和血栓形成也是导致感染严重急性呼吸综合征冠状病毒2的受试者死亡的原因。血小板主要与血栓形成有关。此外，它们可以与病毒相互作用，是炎症介质的重要来源。虽然较低的血小板计数与严重程度和死亡率相关，但对COVID-19期间的血小板功能知之甚少。评估血小板对COVID-19患者炎症和血栓形成的作用。从115名出现非重度（n=71）和重度（n=44）呼吸道症状的COVID-19连续患者中采集血液。我们记录了与COVID-19患者血小板相关的严重急性呼吸综合征冠状病毒2 RNA的存在。对血浆和血小板中细胞因子的详尽评估显示，非重度和重度COVID-19患者的血小板相关细胞因子水平均受到调节，表明血小板对血浆细胞因子负荷有直接贡献。此外，我们证明了血小板在非严重和严重形式的COVID-19中都释放了它们的α颗粒和致密颗粒内容物。与在健康志愿者中测量的浓度相比，暴露于磷脂酰丝氨酸的血小板细胞外囊泡在非重度COVID-19病例中增加，但在重度COVID-19病例中没有增加。D-二聚体的水平，血栓形成的标志物，未能与血小板活化的任何测量指标相关。在功能上，在表现出非重度和重度症状的COVID-19受试者中，血小板过度活化，在次优凝血酶浓度下发生聚集。此外，在流动条件下，血小板更有效地粘附到胶原蛋白涂覆的表面上。总的来说，这些数据表明，血小板处于COVID-19发病机制的前沿，因为它们在疾病的不同阶段释放各种分子。因此，血小板可能有可能导致COVID-19中压倒性的血栓炎症，抑制血小板活化相关途径可能会改善COVID-19期间的结果。
Supplemental Digital Content is available in the text. In addition to the overwhelming lung inflammation that prevails in coronavirus disease 2019 (COVID-19), hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe acute respiratory syndrome coronavirus 2. Platelets are chiefly implicated in thrombosis. Moreover, they can interact with viruses and are an important source of inflammatory mediators. While a lower platelet count is associated with severity and mortality, little is known about platelet function during COVID-19. To evaluate the contribution of platelets to inflammation and thrombosis in patients with COVID-19. Blood was collected from 115 consecutive patients with COVID-19 presenting nonsevere (n=71) and severe (n=44) respiratory symptoms. We document the presence of severe acute respiratory syndrome coronavirus 2 RNA associated with platelets of patients with COVID-19. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in both patients with nonsevere and severe COVID-19, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents in both nonsevere and severe forms of COVID-19. In comparison to concentrations measured in healthy volunteers, phosphatidylserine-exposing platelet extracellular vesicles were increased in nonsevere, but not in severe cases of COVID-19. Levels of D-dimers, a marker of thrombosis, failed to correlate with any measured indicators of platelet activation. Functionally, platelets were hyperactivated in COVID-19 subjects presenting nonsevere and severe symptoms, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions. Taken together, the data suggest that platelets are at the frontline of COVID-19 pathogenesis, as they release various sets of molecules through the different stages of the disease. Platelets may thus have the potential to contribute to the overwhelming thrombo-inflammation in COVID-19, and the inhibition of pathways related to platelet activation may improve the outcomes during COVID-19.