Development of a platform to non-invasively assess microvascular endothelial dysfunction at the bedside in COVID-19 patients throughout intensive care.

摘要/项目摘要 全球COVID-19大流行已导致超过430，000人死亡（二零二零年六月），并产生急性 需要即时技术来评估感染SARS-COV-2的患者。内皮功能障碍是一种 COVID-19的常见并发症，导致中风、急性冠状动脉综合征和血栓事件。 这些后遗症由微血管功能下降介导。微血管功能障碍是常见的 多种病理生理学中终末器官损伤的途径，包括急性呼吸窘迫综合征 （ARDS）和败血症。目前，约35-62%接受呼吸支持的COVID-19 ARDS患者 而不是生存。 微血管功能在重症监护期间没有常规评估。因此，理解伤害 潜在治疗剂的机制和开发受到知识的关键差距的限制， 方法不当。我们的团队最近进行了一项试点研究，以评估COVID-19患者的微血管健康状况。 19例患者，证明了该技术在高要求临床条件下的可行性。目标1 在这个项目中，我们将开发和测试一个平台，该平台将最先进的近红外和漫反射相结合， 将相关光谱学引入到集成的远程控制系统中以监测微血管血液 容积、氧饱和度和血管闭塞期间的流量。这个全面的数据集，不可能 用目前的商业装置获得，将能够将氧气输送的不足和 氧气利用率在目标2中，我们将展示我们的平台在重症监护期间的可用性， 有和没有COVID-19的ARDS患者的感染控制预防措施。这种非侵入性评估 微血管健康将允许连续监测患者，从而能够评估 干预和疾病进展。这样的设备可以很容易地转化为其他诊断：任何 引起微血管功能障碍的疾病或创伤，包括休克和糖尿病性血管病变， 可能会被我们开发的平台评估。 如果成功的话，这个由物理科学家和临床医生组成的跨学科团队的工作将建立一个 在危重病期间连续评估微血管健康的可行性。这些结果将在未来 开发血流动力学监测工具和算法，以支持ARDS和强化治疗的管理 护理单位的病人，最终降低死亡率和发病率。

Abstract/Project Summary The worldwide COVID-19 pandemic has caused over 430,000 deaths (June 2020) and generated an acute need for point-of-care technologies to assess patients infected with SARS-COV-2. Endothelial dysfunction is a common complication of COVID-19, leading to strokes, acute coronary syndrome, and thrombotic events. These sequelae are mediated by decreased microvascular function. Microvascular dysfunction is a common pathway to end organ injury in a variety of pathophysiologies, including acute respiratory distress syndrome (ARDS) and sepsis. Currently, ~35-62% of COVID-19 patients with ARDS who receive respiratory support do not survive. Microvascular function is not routinely assessed during critical care. Thus, understanding of injury mechanisms and development of potential therapeutics are limited by a critical gap in knowledge due to inadequate methods. Our team has recently carried out a pilot study to assess microvascular health in COVID- 19 patients, demonstrating the feasibility of this technique under highly demanding clinical conditions. In Aim 1 of this project, we will develop and test a platform combining state-of-the-art near-infrared and diffuse correlation spectroscopies into an integrated remotely controlled system to monitor microvascular blood volume, oxygen saturation, and flow during vascular occlusion. This comprehensive data set, not possible to obtain with current commercial devices, will enable the separation between deficiencies in oxygen delivery and oxygen utilization. In Aim 2, we will demonstrate the usability of our platform during critical care under infection-control precautions in ARDS patients with and without COVID-19. This non-invasive assessment of microvascular health will allow serial monitoring of patients, enabling assessment of the efficacy of interventions and disease progression. Such a device can readily be translated to other diagnoses: any disease or trauma which causes microvascular dysfunction, including shock and diabetic vasculopathy, could potentially be assessed with the platform we will develop. If successful, the work of this interdisciplinary team of physical scientists and clinicians will establish the feasibility of serially assessing microvascular health during critical illness. These results will in able future development of hemodynamic monitoring tools and algorithms to support management of ARDS and intensive care unit patients, ultimately reducing mortality and morbidity.