Sahai Aditya, Bhandari Rohan, Koupenova Milka, Freedman Jane E, Godwin Matthew, McIntyre Thomas, Chung Mina K, Iskandar Jean-Pierre, Kamran Hayaan, Hariri Essa, Aggarwal Anu, Kalra Ankur, Bartholomew John R, McCrae Keith R, Elbadawi Ayman, Svensson Lars G, Kapadia Samir, Cameron Scott J
Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH.
Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH.
Res Sq. 2020 Dec 23:rs.3.rs-119031. doi: 10.21203/rs.3.rs-119031/v1.
Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of anti-platelet agents in attenuating thrombosis is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction (MI), cerebrovascular accident (CVA), and venous thromboembolism (VTE) in COVID-19. Expression of ACE2 and TMPRSS2 on human platelets were detected by immunoblotting and confirmed by confocal microscopy. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. However, both aspirin and NSAID therapies were associated with increased risk of the combined thrombotic endpoint of (MI), (CVA), and (VTE). Thus, while platelets clearly express ACE2-TMPRSS2 receptor-protease axis for SARS-CoV-2 infection, aspirin does not prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appears distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）是一场持续的病毒性大流行，其特征是血栓形成事件的风险增加。然而，血小板在COVID-19中观察到的血栓形成风险升高中的作用以及抗血小板药物在减轻血栓形成方面的效用尚不清楚。我们旨在确定人类血小板是否在其细胞表面表达已知的SARS-CoV-2受体-蛋白酶轴，并评估阿司匹林的抗血小板作用是否可以减轻COVID-19患者发生心肌梗死（MI）、脑血管意外（CVA）和静脉血栓栓塞（VTE）的风险。通过免疫印迹检测人类血小板上血管紧张素转换酶2（ACE2）和跨膜丝氨酸蛋白酶2（TMPRSS2）的表达，并通过共聚焦显微镜进行确认。我们评估了22072例接受COVID-19检测的有症状患者。进行倾向匹配分析以确定使用阿司匹林或非甾体抗炎药（NSAIDs）治疗是否会影响COVID-19患者的血栓形成结局。阿司匹林和NSAIDs均未影响COVID-19患者的死亡率。然而，阿司匹林和NSAIDs治疗均与心肌梗死（MI）、脑血管意外（CVA）和静脉血栓栓塞（VTE）的联合血栓形成终点风险增加相关。因此，虽然血小板确实表达用于SARS-CoV-2感染的ACE2-TMPRSS2受体-蛋白酶轴，但阿司匹林并不能预防COVID-19患者的血栓形成和死亡。因此，COVID-19中血栓形成的机制似乎不同，血小板作为SARS-CoV-2介导的血栓形成的直接介质的作用值得进一步研究。
