Multiphysics and multiscale modeling of microthrombosis in COVID-19.
Multiphysics and multiscale modeling of microthrombosis in COVID-19.
复制标题
COVID-19中微栓塞的多物理和多尺度建模。
DOI：
10.1371/journal.pcbi.1009892
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发表时间：
2022-03
影响因子：
4.3
通讯作者：
Karniadakis GE
中科院分区：
文献类型：
--
作者：
Li H;Deng Y;Li Z;Dorken Gallastegi A;Mantzoros CS;Frydman GH;Karniadakis GE
新出现的临床证据表明，2019冠状病毒病（COVID-19）患者微血管系统中的血栓形成在决定疾病进展方面起着至关重要的作用。由于SARS-CoV-2的传染性，患者的新鲜血液样本仅限于用于体外实验研究。在本文中，我们采用了一种新的多尺度和多物理计算框架，使用来自COVID-19患者的数据对微血管中的病理性血栓形成进行预测建模。该框架无缝集成了血液凝固过程中的关键组件，包括血液动力学，凝血因子和凝血动力学的运输，血细胞力学和粘附动力学，从而使我们能够量化文献中报道的许多促血栓形成因子的贡献，例如淤滞，血液凝固因子水平和活性的紊乱，内皮细胞和白细胞对COVID-19中微血栓形成的炎症反应。我们的模拟结果表明，在考虑的凝血因子，抗凝血酶和因子V发挥更突出的作用，在促进血栓形成。我们的模拟还表明，白细胞募集到内皮细胞加剧血栓形成，并有助于血液流动的阻塞。此外，我们表明，最近发现的流动血细胞簇可能是白细胞从血栓形成部位分离的结果，这可能是新凝块形成的病灶。这些发现指出了应进一步评估的潜在目标，并在COVID-19患者的抗血栓治疗中优先考虑。总而言之，我们的计算框架为定量理解病理性血栓形成机制提供了强大的工具，并为治疗COVID-19相关血栓形成的新治疗方法提供了见解。新出现的临床证据表明，2019冠状病毒病（COVID-19）患者微血管系统中的血栓形成在决定疾病进展方面起着至关重要的作用。我们采用一种新的多物理场和多尺度计算框架来研究COVID-19中微血栓和循环细胞簇病理形成的潜在机制。我们量化了文献中报道的许多促血栓形成因素的贡献，如停滞，凝血因子水平和活性的紊乱，内皮细胞和白细胞对COVID-19微血栓形成的炎症反应，通过这些因素，我们确定了应进一步评估的潜在靶点，并优先考虑COVID-19患者的抗血栓治疗。
Emerging clinical evidence suggests that thrombosis in the microvasculature of patients with Coronavirus disease 2019 (COVID-19) plays an essential role in dictating the disease progression. Because of the infectious nature of SARS-CoV-2, patients’ fresh blood samples are limited to access for in vitro experimental investigations. Herein, we employ a novel multiscale and multiphysics computational framework to perform predictive modeling of the pathological thrombus formation in the microvasculature using data from patients with COVID-19. This framework seamlessly integrates the key components in the process of blood clotting, including hemodynamics, transport of coagulation factors and coagulation kinetics, blood cell mechanics and adhesive dynamics, and thus allows us to quantify the contributions of many prothrombotic factors reported in the literature, such as stasis, the derangement in blood coagulation factor levels and activities, inflammatory responses of endothelial cells and leukocytes to the microthrombus formation in COVID-19. Our simulation results show that among the coagulation factors considered, antithrombin and factor V play more prominent roles in promoting thrombosis. Our simulations also suggest that recruitment of WBCs to the endothelial cells exacerbates thrombogenesis and contributes to the blockage of the blood flow. Additionally, we show that the recent identification of flowing blood cell clusters could be a result of detachment of WBCs from thrombogenic sites, which may serve as a nidus for new clot formation. These findings point to potential targets that should be further evaluated, and prioritized in the anti-thrombotic treatment of patients with COVID-19. Altogether, our computational framework provides a powerful tool for quantitative understanding of the mechanism of pathological thrombus formation and offers insights into new therapeutic approaches for treating COVID-19 associated thrombosis. Emerging clinical evidence suggests that thrombosis in the microvasculature of patients with Coronavirus disease 2019 (COVID-19) plays an essential role in dictating the disease progression. We employ a novel multiphysics and multiscale computational framework to investigate the underlying mechanism of the pathological formation of microthrombi and circulating cell clusters in COVID-19. We quantify the contributions of many prothrombotic factors reported in the literature, such as stasis, the derangement in blood coagulation factor levels and activities, inflammatory responses of endothelial cells and leukocytes to the microthrombus formation in COVID-19, through which we identify the potential targets that should be further evaluated, and prioritized in the anti-thrombotic treatment of patients with COVID-19.
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影响因子：
4.3
作者：
Chang HY;Li X;Li H;Karniadakis GE
通讯作者：
Karniadakis GE
DOI：
10.1016/j.cma.2010.02.001
发表时间：
2010-06-01
影响因子：
7.2
作者：
Fedosov DA;Caswell B;Karniadakis GE
通讯作者：
Karniadakis GE
影响因子：
4.1
作者：
Lei, Huan;Fedosov, Dmitry A.;Karniadakis, George Em
通讯作者：
Karniadakis, George Em
影响因子：
64.8
作者：
BEGENT, N;BORN, GVR
通讯作者：
BORN, GVR
DOI：
10.1098/rspb.1988.0038
发表时间：
1988-06-22
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DEMBO, M;TORNEY, DC;HAMMER, D
通讯作者：
HAMMER, D