Project Summary/Abstract
Coronavirus 2019 (COVID-19) has infected more than 29 million globally. While the majority of individuals
experience mild symptoms, the presence of obesity among other factors identifies a particularly high-risk group
of individuals for development of severe COVID-19. Severe COVID-19 is characterized by exuberant
inflammation and vascular dysfunction, but long-term cardiovascular effects remain unclear. We hypothesize
that COVID-19 infection has widespread and long-lasting deleterious effects on endothelial function, including
molecular pathways of cellular senescence and inflammation among obese individuals. We propose to
prospectively study 100 obese and non-obese individuals with history of COVID-19 infection and 50 age- and
sex-matched controls. To gain further insights into underlying mechanisms of vascular dysfunction, we will
pursue three related lines of investigation: In Aim 1, we will study the effect of COVID-19 across vascular beds
including peripheral and coronary microvascular function. In Aim 2, we will investigate the association of
COVID-19 and molecular pathways of endothelial activation and senescence using circulating proteomic
profiling, gene expression profiling of freshly isolated human endothelial cells, complemented by interrogation
of targeted endothelial pathways. In Aim 3, we will conduct a prospective longitudinal observational study to
examine the effect of COVID-19 on trajectories of peripheral and coronary microvascular function and
endothelial phenotype over the course of 6 months. This proposal leverages a unique and highly experienced
multidisciplinary team of investigators with expertise in obesity-related cardiovascular disease, endothelial and
aging biology, coronary microvascular dysfunction, and bioinformatics. Importantly, our investigative team has
a track record of successfully enrolling minority participants across two medical centers. With a
disproportionate burden of severe COVID-19 among racial and ethnic minority groups, we will be uniquely
positioned to examine race/ethnic differences in exploratory analyses. These studies have the potential to
provide important insights into mechanisms driving endothelial inflammation and cardiovascular consequences
of COVID-19 among obese individuals and will lay the foundation for future studies focused on long-term
cardiovascular complications and therapeutic strategies.