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 全球新冠肺炎大流行已造成超过43万人死亡(2020年6月)，并产生了严重的 需要护理点技术来评估感染SARS-COV-2的患者。内皮功能障碍是一种 新冠肺炎的常见并发症，导致中风、急性冠脉综合征和血栓事件。 这些后遗症是由微血管功能下降引起的。微血管功能障碍是一种常见的 包括急性呼吸窘迫综合征在内的多种病理生理学的器官损伤终末途径 (ARDS)和败血症。目前，接受呼吸支持的新冠肺炎ARDS患者中，约有35-62% 而不是生存。 在重症监护期间，微血管功能不进行常规评估。因此，对伤害的理解 潜在疗法的机制和发展受到知识严重缺口的限制，这是由于 方法不充分。我们的团队最近进行了一项试验性研究，以评估COVID的微血管健康- 19例患者，证明了该技术在高要求的临床条件下的可行性。在目标1中 在这个项目中，我们将开发和测试一个最先进的近红外和漫反射相结合的平台 将相关光谱仪整合到一个集成的远程控制系统中，以监测微血管血液 血管闭塞时的血容量、血氧饱和度和血流量。这一全面的数据集，不可能 用目前的商业设备获得的，将使氧气输送的缺陷和 氧气利用率。在目标2中，我们将展示我们的平台在以下情况下的危重护理期间的可用性 使用和不使用新冠肺炎的急性呼吸窘迫综合征患者的感染控制预防措施。这种非侵入性的评估 微血管健康将允许对患者进行连续监测，从而能够评估 干预措施和疾病进展。这样的设备可以很容易地转换为其他诊断：任何 引起微血管功能障碍的疾病或创伤，包括休克和糖尿病血管病变，可能 可能会与我们将开发的平台一起进行评估。 如果成功，这个由物理学家和临床医生组成的跨学科团队的工作将建立 危重病期间连续评估微血管健康的可行性。这些成果将在未来取得 开发血流动力学监测工具和算法以支持ARDS和重症监护的管理 护理单元患者，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.