Document text
Principal Investigator: MARK A. ATKINSON
Organization: UNIVERSITY OF FLORIDA
Fiscal Year: 2020
Award: $1,351,492
Funding agency: National Institute of Allergy and Infectious Diseases
Extensive clinical research studies are urgently needed to inform patient management strategies and develop
pharmaceutical countermeasures to combat the 2019 novel coronavirus disease (COVID-19). Currently,
COVID-19 infections and hospitalizations are surging across the state of Florida; hence, we propose to
establish the University of Florida (UF) as a subject-enrollment and sample collection center for the
Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study at three Florida health science
centers. In this nationwide prospective observational study, peripheral blood and nasal swabs will be frequently
collected from consented hospitalized patients with confirmed COVID-19, with endotracheal aspirates also
collected if the patient requires intubation. After participants are discharged, blood and nasal swabs will be
collected during outpatient visits held at three-month intervals over the course of one year, allowing for
longitudinal analysis of the virus’s effects on the immune system both during active infection and following
recovery. Through the OneFlorida Clinical Research Consortium (CRC), we already have established
infrastructure including trained staff to support participant consenting/enrollment and sample collection, as well
as on site laboratory facilities for sample processing. In Aim 1, we propose to integrate three OneFlorida CRC
collection sites (Tampa General Hospital/University of South Florida, UF Health Jacksonville Medical Center,
and UF Health Shands Hospital in Gainesville) into the IMPACC study. These sites have sufficient COVID-19
caseload to support enrollment of 100 participants over the course of the four-month recruitment period. In Aim
2, samples will be processed immediately upon collection and shipped to six core laboratories for precision
medicine genotyping, viral sequencing, proteomics/metabolomics, antibody measurement and isotyping, as
well as immunophenotyping by CyTOF. From these collective data, IMPACC seeks to link viral burden with
immune signatures as biomarkers of acute disease severity, mortality, the development of durable immunity,
and long-term outcomes in survivors. Moreover, extensive immunophenotyping data has the potential to
uncover new therapeutic targets to mitigate the disease severity. Initially, COVID-19 mortality was attributed to
a cytokine storm and enhanced thrombosis, supporting treatment with immunosuppressive drugs in patients
with severe disease. However, in an effort to support the power of immmuophenotyping to provide key
information, we provide preliminary data suggesting that immunosuppression is a primary concordant feature
of the disease, potentially arguing against the routine use of immunosuppressant medications. These data also
demonstrate our ability to perform single cell RNA sequencing (scRNAseq), scATACseq, spectral flow
cytometry, and ELISpot to evaluate gene expression, chromatin accessibility, protein expression, and immune
cell function, respectively. With the consortium’s approval to use residual IMPACC samples, these site-specific
assays could be funded through outside mechanisms and the data shared across the IMPACC consortium.
Terms: <2019 novel coronavirus><2019-nCoV><21+ years old><3-D><3-Dimensional><3D><Acute><Acute Disease><Address><Adult><Adult Human><Allergy><Annual Reports><Antibodies><Aspirate><Aspirate substance><Assay><Asthma><Autoimmune Diseases><Bioassay><Biologic Assays><Biological Assay><Biological Markers><Blood><Blood Reticuloendothelial System><Body Tissues><Brittle Diabetes Mellitus><Bronchial Asthma><COVID><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID19><COVID19 epidemic><COVID19 pandemic><Cancers><Cell Function><Cell Process><Cell physiology><Cellular Function><Cellular Physiology><Cellular Process><Chromatin><Clinical Research><Clinical Study><CoV disease><Cohort Studies><Collection><Communication><Communication Programs><Communities><Concurrent Studies><Consent><Core Facility><Data><Data Base Management><Data Base Management Systems><Data Bases><Data Collection><Data Protection><Data Set><Database Management Systems><Databases><Dataset><Development><Disease><Disorder><Drugs><Elements><Emergent Technologies><Emerging Technologies><Enrollment><Ensure><Evaluation><Feedback><Florida><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Foundations><Funding><Gene Expression><General Hospitals><Generations><Genetic><Genotype><Goals><Grant><Health><Health Sciences><Healthcare><History><Hospital Admission><Hospitalization><Hospitals><HuBMAP><Human><Human BioMolecular Atlas Program><Hypersensitivity><IDDM><IRB><IRBs><Immune><Immune response><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunologic Subtyping><Immunological><Immunological response><Immunologically><Immunologics><Immunophenotyping><Immunosuppressants><Immunosuppression><Immunosuppression Effect><Immunosuppressive Agents><Immunosuppressive Effect><Individual><Infection><Infrastructure><Institutional Review Boards><Insulin-Dependent Diabetes Mellitus><Intubation><Investigators><Juvenile-Onset Diabetes Mellitus><Ketosis-Prone Diabetes Mellitus><Laboratories><Leadership><Link><Lymph><Lymph Node Reticuloendothelial System><Lymph Reticuloendothelial System><Lymph node proper><Lymphatic System><Lymphatic System Reticuloendothelial System><Lymphatic nodes><Lymphocyte><Lymphocytic><Malignant Neoplasms><Malignant Tumor><Measurement><Mediating><Medical History><Medical center><Medication><Metabolic><Mission><Modern Man><Monitor><NIAID><NIH><Nasal><Nasal Passages Nose><National Institute of Allergy and Infectious Disease><National Institutes of Health><Newsletter><Nose><Observation research><Observation study><Observational Study><Observational research><On-Line Systems><Online Systems><Operations Research><Organ><Organ Donations><Organ Procurements><Out-patients><Outcome><Outpatients><Participant><Pathogenesis><Patients><Peripheral><Personal Medical History><Personal Medical History Epidemiology><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phenotype><Physiologic><Physiological><Physiology><Process><Program Reviews><Progress Reports><Prospective cohort><Proteomics><Public Health><Publications><Race><Racial Group><Racial Stocks><Recommendation><Recording of previous events><Recovery><Research><Research Personnel><Research Resources><Researchers><Residual><Residual state><Resource Allocation><Resources><Respiratory System, Nose, Nasal Passages><Role><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Schedule><Scheme><Scientific Publication><Services><Severe acute respiratory syndrome coronavirus 2><Severity of illness><Ships><Site><Spleen><Spleen Reticuloendothelial System><Structure><Subcellular Process><Sudden-Onset Diabetes Mellitus><Survivors><Swab><T1 DM><T1 diabetes><T1D><T1DM><Therapeutic Intervention><Thrombosis><Thymus><Thymus Gland><Thymus Proper><Thymus Reticuloendothelial System><TimeLine><Tissues><Training><Trust><Type 1 Diabetes Mellitus><Type 1 diabetes><Type I Diabetes Mellitus><United States National Institutes of Health><Universities><University Hospitals><Viral><Viral Burden><Viral Load><Viral Load result><Virus><Visit><Work><Writing><Wuhan coronavirus><acute disease/disorder><acute disorder><adulthood><allergic/immunologic body system><allergic/immunologic organ system><autoimmune disorder><bio-markers><biologic marker><biomarker><cohort><combat><conference><convention><corona virus disease><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><cytokine release syndrome><cytokine storm><data base><data sharing><database management><database systems><design><designing><developmental><disease severity><drug/agent><endotracheal><enroll><experience><flow cytophotometry><health care><host response><immune suppression><immune suppressive agent><immune suppressor><immunophenotype><immunoresponse><immunosuppressive substance><immunosuppressor><improved><insulin dependent diabetes><intervention therapy><juvenile diabetes><juvenile diabetes mellitus><ketosis prone diabetes><knowledge of results><laboratory facility><longitudinal analysis><lymph cell><lymph gland><lymph nodes><lymphatic fluid><lymphnodes><malignancy><meetings><member><metabolism measurement><metabolomics><metabonomics><mortality><neoplasm/cancer><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><online computer><organ development><organ growth><pathogen><peripheral blood><precision medicine><precision-based medicine><programs><prospective><protein expression><recruit><relational database management systems><research study><sample collection><scRNA-seq><sex><single cell RNA-seq><single cell RNAseq><single-cell RNA sequencing><social role><specimen collection><success><summit><symposia><symposium><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><three dimensional><thrombotic disease><thrombotic disorder><type I diabetes><type one diabetes><web based><webinar>