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Principal Investigator: ELAINE F REED
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2020
Award: $208,861
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
The COVID-19 clinical syndrome caused by the SARS-CoV-2 virus has the potential to cause significant
morbidity and mortality in previously healthy patients. A significant observation is that although this infection
may result in a self-limiting upper respiratory infection or mild pneumonia in some patients, other patients
experience progression of respiratory symptoms to requirement of intubation for mechanical respiratory
support and death due to severe respiratory failure. This clinical observation strongly suggests that differences
in host immunologic response are the determinative factor in clinical outcome. We hypothesize that the
proposed systems immunology, biostatistical and computational modeling approaches, coupled with detailed
clinical phenotype of hospitalized COVID-19 patients will provide a new framework to interpret the interplay
between SARS-CoV-2 virus and the host, and the relationship with clinical outcome. Project 1 will assess the
frequency and function of SARS-CoV-2 virus antigen specific T cells and evaluate their breadth and clonality
of their TCR repertoire with clinical outcome. Project 2 will determine epigenetic signatures of the immune
response to the SARS-CoV-2 virus across short, middle and long-term times and identify DNA methylation-
based markers of anti-viral immunity and clinical outcome. With this approach, we will create a unique resource
of highly annotated longitudinal data on SARS-CoV-2 virus infection, which will enable the development of
novel diagnostic strategies and therapeutics to treat or prevent SARS-CoV-2 virus infection.
Terms: <2019 novel coronavirus><2019-nCoV><Affect><Antibodies><Antibody Repertoire><Assay><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bioassay><Biologic Assays><Biological Assay><Biological Markers><Biometrics><Biometry><Biostatistics><Blood Plasma><Blood Sample><Blood specimen><CMV><COVID-19><COVID19><CRG-2><CXCL10><CXCL10 gene><Cell Body><Cells><Cellular Immune Function><Cessation of life><Characteristics><Clinical><Clinical Data><Clonality><Collaborations><Communities><Computer Models><Computerized Models><Coupled><Creatinine><Critical Illness><Critically Ill><Cytomegalovirus><Cytosine><DNA><DNA Methylation><DNA Recombination><Data><Death><Deoxyribonucleic Acid><Development><Disease><Disease Outbreaks><Disease Progression><Disorder><Early Diagnosis><Enrollment><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Evaluation><Fatality rate><Frequencies><Genetic Recombination><Grant><HCMV><HHV 5><HHV5><Host Factor><Host Factor Protein><Human Herpesvirus 5><IFI10><INP10><IP-10><Immune><Immune Globulins><Immune response><Immunes><Immunochemical Immunologic><Immunoglobulin V(D)J Rearrangement><Immunoglobulins><Immunologic><Immunologic Subtyping><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Immunophenotyping><Infection><Injury to Kidney><Integration Host Factors><Intubation><Investigators><Kidney><Kidney Grafting><Kidney Transplantation><Kidney Transplants><Kidney Urinary System><Letters><Link><Lung><Lung Respiratory System><MAC393 antigen><MHC Receptor><MOB-1><Major Histocompatibility Complex Receptor><Measures><Mechanics><Medical><Meta-Analysis><Methylation><Morbidity><Morbidity - disease rate><NIAID><Names><National Institute of Allergy and Infectious Disease><Observation research><Observation study><Observational Study><Observational research><Organ><Outbreaks><Outcome><Pathogenesis><Pathogenicity><Patients><Persons><Phenotype><Plasma><Plasma Serum><Pneumonia><Population><Predisposing Factor><Proteins><Receptors, Antigen, T-Cell><Recombination><Renal Grafting><Renal Transplantation><Renal Transplants><Research Personnel><Research Resources><Researchers><Resources><Respiratory Failure><Respiratory Signs and Symptoms><Reticuloendothelial System, Serum, Plasma><Risk><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><SCYB10><SGP-2 protein><SGP2><SP 40,40 protein><Salivary Gland Viruses><Sampling><Schedule><Series><Severe acute respiratory syndrome coronavirus 2><Severities><Severity of illness><Syndrome><System><T-Cell Receptor><T-Cells><T-Lymphocyte><T-cell receptor repertoire><TCR repertoire><TRPM-2 protein><TRPM2><Technology><Testing><Therapeutic><Time><Transplant Recipients><Upper Respiratory Infections><Upper Respiratory Tract Infection><Urine><Urine Urinary System><V(D)J Rearrangement><V(D)J Recombination><VDJ rearrangement><VDJ recombination><Variant><Variation><Viral Antigens><Viral Diseases><Virus><Virus Diseases><Wuhan coronavirus><X-ray-inducible protein 8><XIP8 protein><airway symptom><anti-viral immunity><antigen-specific T cells><antiviral immunity><apoJ protein><apolipoprotein J><base><bio-markers><biologic marker><biomarker><clinical phenotype><clinical research site><clinical site><clusterin><cohort><complement lysis inhibitor><complement-associated protein SP-40,40 protein><computational modeling><computational models><computer based models><computerized modeling><corona virus disease 2019><coronavirus disease 2019><cytomegalovirus group><damage to kidney><design><designing><developmental><disease severity><early detection><enroll><experience><gIP-10><global health><host response><immune function><immunogenicity><immunophenotype><immunoresponse><injury to organs><ionizing radiation-induced protein-8><kidney damage><kidney injury><kidney tx><mechanical><mortality><new diagnostics><next generation diagnostics><novel><novel diagnostics><organ injury><outcome prediction><parent grant><predictive outcomes><predictors of outcomes><prevent><preventing><protein metabolite><pulmonary><pulmonary failure><pulmonary symptom><renal><renal damage><renal injury><respiratory><respiratory insufficiency/failure><respiratory symptom><response><sample collection><specimen collection><sulfated glycoprotein 2><testosterone-repressed prostate message-2 protein><thymus derived lymphocyte><transplant patient><viral infection><virus antigen><virus infection><virus-induced disease>