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Principal Investigator: CRAIG B THOMPSON
Organization: SLOAN-KETTERING INST CAN RESEARCH
Fiscal Year: 2020
Award: $177,000
Funding agency: National Cancer Institute
Novel Coronavirus 2019 SARS-CoV-2 (COVID-19) infection is a global pandemic disease that has severely affected the United States. Emerging data suggests that racial and ethnic minority groups are disproportionately affected by COVID-19 and African Americans (AA) are overrepresented among hospitalized patients. The clinical symptoms vary from mild in approximately 80% of cases to critically ill. Established risk factors are age, gender and several comorbidities including cancer. Many other factors in clinical severity remain unexplained. This proposal will leverage remnant biospecimens from laboratory-proven COVID-19 positive individuals at Quest Diagnostics, a national commercial laboratory that has performed over 3.75 million COVID-19 tests and has identified over 298,000 positive cases to date, to study host-genetics of COVID19. We expect to include >7500 samples with whole genome genotyping, performed in collaboration with intramural NCI. While there are no established predictors of severity, certain biomarkers from total blood count have been observed to correlate with worse outcomes. Several studies have reported the role of uncontrolled cytokine release to be correlated with poor outcome. We will incorporate biomarkers such as lymphocyte count, neutrophil count and other inflammation markers to develop a severity score. Using this severity score, we will classify individuals as having mild, severe or critical infection. Biospecimens with de-identified clinical data from Quest and vital status data from the National Death Index in the 28 days period from testing positive, will be utilized to determine whether host genetic factors modify COVID-19 outcomes. We will discover novel genetic variation and clonal hematopoiesis (CH) associated with infection severity, mortality and cytokine storm. Finally, we will compare these novel genetic biomarkers in a cancer cohort of 2,000 individuals from MSKCC to contrast COVID-19 specific outcomes in cancer care. This study represents one of the largest COVID-19 cohorts for genetic association studies. These data will be used to compare genetic diversity and the role it plays in COVID-19 severity and will add to the understanding of constitutional determinants of host immune response to mild and severe viral infection and inflammation.
Terms: <2019 novel coronavirus><2019-nCoV><Affect><African American><Afro American><Afroamerican><Age Factors><American><Antibodies><Biological><Biological Markers><Black Populations><Blood><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood Reticuloendothelial System><COVID><COVID-19><COVID19><Cancer Patient><Cancers><Cardiovascular Diseases><Cell Body><Cells><Cessation of life><Chronic><Clinical><Clinical Data><Clinical genetics><CoV disease><Collaborations><Constitutional><Critical Illness><Critically Ill><DCEG><DNA><Data><Data Bases><Databases><Death><Deoxyribonucleic Acid><Derivation><Derivation procedure><Diagnosis><Diagnostic><Disease><Disorder><Division of Cancer Epidemiology and Genetics><Ensure><Funding><Future><GWA study><GWAS><Gender><Gene variant><Genetic><Genetic Alteration><Genetic Change><Genetic Diversity><Genetic Markers><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Susceptibility><Genetic Variation><Genetic defect><Genomics><Genotype><Haplotypes><Hematopoiesis><Hematopoietic Cellular Control Mechanisms><Heritability><Hospital Admission><Hospitalization><IRB><IRBs><Immune response><Immune system><Immunologic Tests><Immunological Tests><Immunological response><Individual><Infection><Inflammation><Inflammatory><Infrastructure><Inherited Predisposition><Inherited Susceptibility><Institutional Review Boards><Laboratories><Lymphocyte Count><Lymphocyte Number><MSKCC><Malignant Neoplasms><Malignant Tumor><Marrow Neutrophil><Mediator><Mediator of Activation><Mediator of activation protein><Medical Genetics><Memorial Sloan-Kettering Cancer Center><Metabolic><Minority Groups><Mutation><NHGRI><NIH><National Center for Human Genome Research><National Human Genome Research Institute><National Institutes of Health><Neutrophilic Granulocyte><Neutrophilic Leukocyte><New York><Oral><Outcome><Pathway interactions><Patients><Play><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Predisposition><Protocol><Protocols documentation><RT-PCR><RTPCR><Reporting><Research><Reverse Transcriptase Polymerase Chain Reaction><Risk><Risk Factors><Role><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><SNP array><SNP chip><SNP genotyping><Sample Size><Sampling><Severe acute respiratory syndrome coronavirus 2><Severities><Severity of illness><Somatic Mutation><Statistical Methods><Stratification><Susceptibility><Swab><Symptoms><Testing><Therapeutic><Total Lymphocyte Count><United States><United States National Institutes of Health><Variant><Variation><Viral Diseases><Virus Diseases><Vital Status><Wuhan coronavirus><age dependent><age related><allele variant><allelic variant><allergic/immunologic body system><allergic/immunologic organ system><bio-markers><biologic marker><biomarker><black American><blood cell formation><cancer care><cardiovascular disorder><co-morbid><co-morbidity><cohort><comorbidity><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><cytokine><cytokine release syndrome><cytokine storm><data base><disease severity><entire genome><ethnic minority><ethnic minority population><full genome><genetic association><genetic biomarker><genetic epidemiologic study><genetic epidemiology><genetic etiology><genetic mechanism of disease><genetic variant><genetic vulnerability><genetically predisposed><genome mutation><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><genomic data><genomic data-set><genomic dataset><genomic variant><host response><immunoresponse><indexing><inflammation marker><inflammatory marker><insight><malignancy><mortality><neoplasm/cancer><neutrophil><novel><pandemic><pandemic disease><pathway><polygenic risk score><prospective><racial minority><reverse transcriptase PCR><single nucleotide polymorphism array><single nucleotide polymorphism chip><single nucleotide polymorphism genotyping><social role><viral infection><virus infection><virus-induced disease><whole genome><whole genome association analysis><whole genome association studies><whole genome association study>