SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

作者：Si Zhang, Si Zhang, Yangyang Liu, Xiaofang Wang, Haishan Li, Haishan Li, Yuyan Wang, Mengduan Liu, Xiaoyan Zhao, Youhua Xie, Yan Yang, Shenghui Zhang, Shenghui Zhang, Zhenghong Yuan, Zhongren Ding, Zhenghong Yuan, Zhongren Ding, Yi Zhang, Liang Hu · 发表于：Journal of Hematology & Oncology · 年份：2020 · DOI：10.1186/s13045-020-00954-7 · 被引用次数：685 · 研究领域：COVID-19 Clinical Research Studies、Heparin-Induced Thrombocytopenia and Thrombosis、Platelet Disorders and Treatments

BACKGROUND: Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. METHODS: -induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. RESULTS: We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression de...