Document text
Principal Investigator: Vincent C Bond
Organization: MOREHOUSE SCHOOL OF MEDICINE
Fiscal Year: 2021
Award: $177,500
Funding agency: National Institute on Minority Health and Health Disparities
Abstract: Diversity in the rates of progression and mortality of COVID-19 disease within infected African
American (AAs) subgroups are clearly not just a function of the underlying health conditions that increase the
rate of mortality for COVID -19 patients, such as hypertension, obesity and diabetes, but may also be affected
by host genetic factors. Here we propose a series of studies to advance the understanding of our knowledge in
relative to the health inequity in COVID-19 disease. This is a multiple-collaborative study between Genomic,
Imaging research labs and Statistical studies. Research teams in Morehouse School of Medicine (MSM) have
established intimate relationships that position the institute to focus their research works on underserved
minorities. We plan to develop and disseminate technological approaches in identifying host factors that
disproportionately affect AAs COVID-19 infected patients. Given that the discovery, and establishment of
translational implementation of novel solutions to health disparities in high-risk minority COVID-19 infected is our
overall goals. Recently, angiotensin-converting enzyme 2 (ACE2), encoded on the X-chromosome, has been
shown to be a functional receptor for COVID-19 to enter host target cells and the concern might arise regarding
whether ACE2 variants between and within subgroups would increase the morbidity and mortality of COVID-19
infected patients. Therefore, the long-term goal is to compare how genetic variants of the ACE2 receptor,
chemokine (CCL2) and human leukocyte antigen (HLA) genes (influence the immune system’s response to
viruses and bacteria), affects COVID-19 disease severity among people but no underlining disease like diabetes,
heart or lung disease with those with mild or no disease manifestations. Short-term goal; we will focus on two
aims; Aim: 1-Determine genetic variations in ACE2 gene on obtained DNA samples from COVID-19
infected patients and evaluate for potential correlation between ACE2 variant frequencies in relationship
to COVID-19 disease progression and mortalities between and within AAs and non-Hispanic Caucasian
CAs subgroup;. COVID-19 is caused by SARS-CoV-2 which uses host cell ACE2, TMPRSS2, EZRIN and other
proteins for entry. Differences in ACE2 or TMPRSS2/EZRIN genes expression and SNPs may justify the disease
disparity and aim 2 will address how COVID-19 spike engagement with host cell receptor is precisely regulated
and how host cells respond to cytokines elicited by COVID-19 infection using lung organoids. A recent correlation
study suggested that the decrease expression of ACE2 /TMPRSS2/EZRIN are predictors of decreased
susceptibility to COVID-19 infection and could be attributed to COVID-19 morbidity in Africa American patients.
Aim-2: Modeling COVID-19-elicited disease disparity using lung organoids. Clinical validation of ACE2 and
EZRIN will help to develop better strategies for COVID 19 diagnosis and treatment to reduce the observed
COVID-19 disease progressive outcome and mortality gaps between African American and Caucasians patients.
.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><Address><Affect><Africa><African American><Afro American><Afroamerican><American><Bacteria><Biology><Black Populations><Blood Sample><Blood specimen><CCL2><CCL2 gene><COVID associated morbidity><COVID disease severity><COVID induced morbidity><COVID infected patient><COVID morbidity><COVID patient><COVID positive patient><COVID related morbidity><COVID severity><COVID-19><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated morbidity><COVID-19 associated mortality><COVID-19 death><COVID-19 diagnosis><COVID-19 disease severity><COVID-19 fatality><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced morbidity><COVID-19 induced mortality><COVID-19 infected patient><COVID-19 infection><COVID-19 morbidity><COVID-19 mortality><COVID-19 patient><COVID-19 positive patient><COVID-19 related death><COVID-19 related fatality><COVID-19 related morbidity><COVID-19 related mortality><COVID-19 severity><COVID-19 therapy><COVID-19 treatment><COVID-19 virus><COVID19><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 death><COVID19 diagnosis><COVID19 disease severity><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 patient><COVID19 positive patient><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 severity><COVID19 therapy><COVID19 treatment><COVID19 virus><CV-19><CV19><Cardiac Diseases><Cardiac Disorders><Caucasian><Caucasian Race><Caucasians><Caucasoid><Caucasoid Race><Cell Body><Cells><Center for Translational Science Activities><Chemokine, CC Motif, Ligand 2><Chemotactic Cytokines><Clinical><CoV-2><CoV2><Correlation Studies><DNA><Data><Deoxyribonucleic Acid><Diabetes Mellitus><Disease><Disease Progression><Disorder><Epitheliasin Gene><Female><Frequencies><Gene Expression><Gene variant><Genes><Genetic><Genetic Diversity><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Susceptibility><Genetic Variation><Genomics><Goals><HL-A Antigens><HLA Antigens><Health><Health Inequity><Heart Diseases><Homologous Chemotactic Cytokines><Hospitals><Host Factor><Host Factor Protein><Human Leukocyte Antigens><Hypertension><Image><Immune response><Immunological response><Incidence><Individual><Inequalities in Health><Inequities in Health><Inherited Predisposition><Inherited Susceptibility><Institutes><Integration Host Factors><Intercrines><Knowledge><Leukocyte Antigens><Lung><Lung Respiratory System><Lung diseases><MCAF><MCP-1><MCP1><Minority><Modeling><Molecular><Monocyte Chemoattractant Protein-1><Monocyte Chemotactic Protein-1><Monocyte Chemotactic and Activating Factor><Monocyte Chemotactic and Activating Protein><Monocyte Chemotactive and Activating Factor><Monocyte Secretory Protein JE><Morbidity><Morbidity - disease rate><Morehouse Sch of 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Correlation><Statistical Study><Subgroup><Susceptibility><TMPRSS2><TMPRSS2 gene><Testing><Validation><Variant><Variation><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Virus><Work><Wuhan coronavirus><X Chromosome><adiposity><allele variant><allelic variant><angiotensin converting enzyme 2><angiotensin converting enzyme II><black American><chemoattractant cytokine><chemokine><co-morbid><co-morbidity><comorbidity><computer based prediction><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated morbidity><coronavirus disease 2019 associated mortality><coronavirus disease 2019 death><coronavirus disease 2019 diagnosis><coronavirus disease 2019 disease severity><coronavirus disease 2019 fatality><coronavirus disease 2019 induced death><coronavirus disease 2019 induced fatality><coronavirus disease 2019 induced morbidity><coronavirus disease 2019 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