Rapid Detection and Inhibition of SARS-CoV-2-Spike Mutation-Mediated Microthrombosis.
Rapid Detection and Inhibition of SARS-CoV-2-Spike Mutation-Mediated Microthrombosis.
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快速检测和抑制 SARS-CoV-2 尖峰突变介导的微血栓形成。
DOI：
10.1002/advs.202103266
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Hsiai TK
中科院分区：
文献类型：
--
作者：
Satta S;Lai A;Cavallero S;Williamson C;Chen J;Blázquez-Medela AM;Roustaei M;Dillon BJ;Ashammakhi N;Carlo DD;Li Z;Sun R;Hsiai TK
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染后内皮细胞的激活被认为是2019冠状病毒病患者中日益被认识到的血栓性并发症的主要驱动因素，可能是由于SARS-CoV-2刺突蛋白与人血管紧张素转换酶2（hACE 2）结合。疫苗接种疗法使用相同的刺突序列或蛋白质来增强宿主免疫应答，作为对抗SARS-CoV-2感染的保护机制。因此，接种疫苗后报告了血栓形成事件病例。尽管疫苗通常被认为是安全的，但由于遗传异质性、年龄或全球人群中存在合并症，预测患者的严重不良结局仍然是一个挑战。为了阐明患者特异性血管血栓形成的刺突蛋白，使用涂覆有人内皮细胞并暴露于患者特异性全血的新型微流体平台来重现人微循环环境。在此，在暴露于纳米颗粒中的刺突蛋白和病毒载体中的刺突变体D 614 G后测试了血液凝固效果，并且使用活的SARS-CoV-2证实了结果。值得注意的是，还检查了通过使用纳米脂质体-hACE 2和抗白细胞介素（IL）6抗体来减少血凝块形成的两种潜在策略。SARS-CoV-2感染导致COVID-19患者中越来越多的血栓并发症，这可能是由于SARS-CoV-2刺突蛋白与人血管紧张素转换酶2结合所致。基于加标的疫苗接种疗法可能导致类似的结果。在微流体平台中暴露于患者特定血液的内皮化通道可用于快速测试血液凝固，预测血栓形成事件。
Activation of endothelial cells following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is thought to be the primary driver for the increasingly recognized thrombotic complications in coronavirus disease 2019 patients, potentially due to the SARS‐CoV‐2 Spike protein binding to the human angiotensin‐converting enzyme 2 (hACE2). Vaccination therapies use the same Spike sequence or protein to boost host immune response as a protective mechanism against SARS‐CoV‐2 infection. As a result, cases of thrombotic events are reported following vaccination. Although vaccines are generally considered safe, due to genetic heterogeneity, age, or the presence of comorbidities in the population worldwide, the prediction of severe adverse outcome in patients remains a challenge. To elucidate Spike proteins underlying patient‐specific‐vascular thrombosis, the human microcirculation environment is recapitulated using a novel microfluidic platform coated with human endothelial cells and exposed to patient specific whole blood. Here, the blood coagulation effect is tested after exposure to Spike protein in nanoparticles and Spike variant D614G in viral vectors and the results are corroborated using live SARS‐CoV‐2. Of note, two potential strategies are also examined to reduce blood clot formation, by using nanoliposome‐hACE2 and anti‐Interleukin (IL) 6 antibodies. SARS‐CoV‐2 infection drives the increasingly recognized thrombotic complications in COVID‐19 patients, potentially due to the SARS‐CoV‐2 Spike protein binding to human angiotensin‐converting enzyme 2. Vaccination therapies that are spike‐based can lead to a similar outcomes. Endothelialized channels exposed to patient specific blood in microfluidic platforms can be used to rapidly test for blood coagulation, predicting thrombotic events.
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影响因子：
3.5
作者：
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影响因子：
39.3
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64.5
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