Cardiovascular Risk, Vascular and Kidney Damage in COVID-19 Survivors

PROJECT SUMMARY The coronavirus disease 2019 (COVID-19) pandemic is a public health crisis, characterized by pneumonia and multiorgan dysfunction. We previously demonstrated that community-acquired pneumonia increases the long- term risk of cardiovascular disease. There is an urgent need to investigate the incidence and mechanisms of cardiovascular disease in COVID-19 survivors. Thus, we propose a novel investigation of the intermediate and long-term cardiac, vascular, and renal consequences of COVID-19. Acutely, COVID-19 is associated with microvascular and macrovascular thrombotic events and inflammatory- and stress-related injury in the heart, kidneys, and vasculature that may put COVID-19 survivors at particularly elevated risk of chronic complications. Our study team has combined expertise in the study of post-pneumonia cardiovascular risk, vascular and kidney pathophysiology, epidemiologic outcomes research, and implementation of longitudinal prospective cohort studies. Our goal is to examine the natural history of cardiac, vascular, and kidney disease in COVID-19 survivors, and to identify risk factors for adverse longitudinal outcomes in these patients. We propose a prospective cohort study evaluating 1) cardiovascular events in a large, electronic health record-based cohort of survivors of COVID-19 in our health system compared with matched controls ("MACE cohort") and 2) detailed vascular and renal phenotyping in a smaller cohort of COVID- 19 survivors compared with matched controls ("deep phenotyping cohort"). In the MACE cohort, we will collect detailed hospitalization, demographic, and clinical data as well as records for post-COVID-19 hospitalizations. An expert physician panel will prospectively adjudicate hospitalization records to evaluate for post-COVID-19 MACE (heart failure hospitalization, acute coronary syndrome, serious arrhythmia, stroke, peripheral artery disease, and death). In the deep phenotyping cohort, we will perform serial quantitative measurements of vascular health in large, medium-sized, and small arteries, specifically: (1) pulse wave velocity (the reference standard measure of large artery stiffness), (2) flow-mediated dilation (a measure of endothelial function), and (3) microvascular structure assessed by sublingual imaging. We will also perform serial measurements of kidney function (estimated glomerular filtration rate, albuminuria, markers of tubular injury, and exploratory ultrasound images to estimate fibrosis). We aim to assess the long-term incidence of and risk factors for MACE in COVID- 19 survivors, and to evaluate the trajectory of microvascular and macrovascular health and kidney function over time in these patients. Our mechanism-driven approach will provide critical guidance on longitudinal cardiovascular risk and vascular and kidney damage following COVID-19 infection. The results of this study will enhance our understanding of the long-term target organ effects of COVID-19 and identify risk factors that can be targeted by future interventions to ultimately reduce the risk of adverse outcomes in COVID-19 survivors.