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.
The 2019 novel coronavirus disease (COVID-19) pandemic represents the greatest public health crisis of our generation, requiring urgent mobilization to investigate its immunological and physiological effects during both acute symptomatic infection and following recovery, and accordingly, the current surge in COVID-19 infections and hospitalizations across the state of Florida supports the participation of the University of Florida (UF), along with the OneFlorida Clinical Research Consortium (CRC), in the NIAID-supported Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) prospective clinical study. We propose to collect medical history as well as peripheral blood, nasal swabs, and endotracheal aspirates (when available) from 100 adult participants who are hospitalized due to COVID-19 at one of our three OneFlorida sites: Tampa General Hospital/University of South Florida (USF, Tampa), UF Health Shands Hospital (Gainesville), and UF Health Jacksonville Medical Center (Jacksonville). Samples will be collected as put forth by the IMPACC, processed on site, and shipped to the designated IMPACC core facilities where immunological assessments will be performed in order to identify immunological signatures of disease course or mortality, and to identify new potential targets for therapeutic intervention.
