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

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.