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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.
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