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Principal Investigator: Naomi Miriam Hamburg
Organization: BETH ISRAEL DEACONESS MEDICAL CENTER
Fiscal Year: 2024
Award: $663,087
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ADAMTS><Acceleration><Acute><Adverse effects><Age><Aging><Automobile Driving><Autopsy><Bio-Informatics><Bioinformatics><Biology of Aging><Blood Plasma><Blood Vessels><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 effect><COVID-19 impact><COVID-19 impacted><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 predisposition><COVID-19 sequelae><COVID-19 susceptibility><COVID-19 virus><COVID-19 virus infection><COVID-19 vulnerability><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cardiac><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular Physiology><Cardiovascular system><Case-Base Studies><Case-Comparison Studies><Case-Compeer Studies><Case-Referent Studies><Case-Referrent Studies><Case/Control Studies><Cell Aging><Cell Body><Cell Senescence><Cells><Cellular Aging><Cellular Senescence><Cessation of life><Clinical><CoV-2><CoV2><Coronary><Coronaviridae><Coronavirus><Coronavirus Infectious Disease 2019><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Critical Illness><Critically Ill><D-dimer><D-dimer fibrin><D-dimer fragments><Death><Development><Diathesis><Dimethylbiguanidine><Dimethylguanylguanidine><Disease><Disease susceptibility><Disorder><Elements><Endogenous Nitrate Vasodilator><Endothelial Cells><Endothelium><Endothelium-Derived Nitric Oxide><Event><Fibrin fragment D><Foundations><Future><Gene Expression><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Heart><Heart Vascular><Human><Image><Individual><Inflammation><Inflammatory><Insulin Resistance><Investigation><Investigators><Kidney><Kidney Urinary System><Lead><Link><Longitudinal observation study><Longitudinal, observational study><Lung><Lung Respiratory System><Medical center><Metabolic dysfunction><Metformin><Microvascular Dysfunction><Minority Enrollment><Modern Man><Molecular><Mononitrogen Monoxide><N,N-dimethyl-imidodicarbonimidic diamide><Nitric Oxide><Nitrogen Monoxide><Nitrogen Protoxide><Non obese><Nonobese><Obesity><Obesity associated cardiovascular disease><Obesity related cardiovascular disease><Oxidative Stress><PET><PET Scan><PET imaging><PETSCAN><PETT><Participant><Pathway interactions><Patients><Pb element><Peripheral><Phenotype><Plasma><Plasma Serum><Position><Positioning Attribute><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Predisposition><Preventive><Production><Prospective Studies><Proteomics><Rad.-PET><Recombinants><Recovery><Replicative Senescence><Research><Research 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DD><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><gene complementation><gene expression analysis><gene expression assay><hCoV19><heavy metal Pb><heavy metal lead><high BMI><high body mass index><high risk group><high risk individual><high risk people><high risk population><history of COVID infection><history of COVID-19 infection><imaging><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><insight><insulin resistant><insulin tolerance><liability to disease><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><microvascular complications><microvascular disease><molecular phenotype><multidisciplinary><nCoV2><necropsy><obese individuals><obese patients><obese people><obese person><obese population><obese subjects><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><patients with obesity><persistent symptom><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><post SARS-CoV-2 infection><postmortem><predisposed to Coronavirus disease 2019><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><prospective><public health relevance><pulmonary><race based differences><race differences><race related differences><racial difference><racial minority group><racial minority individual><racial minority people><racial minority population><racially different><renal><response><senescence><senescent><sequelae following COVID-19><sequelae following SARS-CoV-2 infection><sequelae of COVID-19><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 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