Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC)

Extensive clinical research studies are urgently needed to inform patient management strategies and developpharmaceutical 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 toestablish the University of Florida (UF) as a subject-enrollment and sample collection center for theImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study at three Florida health sciencecenters. In this nationwide prospective observational study, peripheral blood and nasal swabs will be frequentlycollected from consented hospitalized patients with confirmed COVID-19, with endotracheal aspirates alsocollected if the patient requires intubation. After participants are discharged, blood and nasal swabs will becollected during outpatient visits held at three-month intervals over the course of one year, allowing forlongitudinal analysis of the virus's effects on the immune system both during active infection and followingrecovery. Through the OneFlorida Clinical Research Consortium (CRC), we already have establishedinfrastructure including trained staff to support participant consenting/enrollment and sample collection, as wellas on site laboratory facilities for sample processing. In Aim 1, we propose to integrate three OneFlorida CRCcollection 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-19caseload to support enrollment of 100 participants over the course of the four-month recruitment period. In Aim2, samples will be processed immediately upon collection and shipped to six core laboratories for precisionmedicine genotyping, viral sequencing, proteomics/metabolomics, antibody measurement and isotyping, aswell as immunophenotyping by CyTOF. From these collective data, IMPACC seeks to link viral burden withimmune 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 touncover new therapeutic targets to mitigate the disease severity. Initially, COVID-19 mortality was attributed toa cytokine storm and enhanced thrombosis, supporting treatment with immunosuppressive drugs in patientswith severe disease. However, in an effort to support the power of immmuophenotyping to provide keyinformation, we provide preliminary data suggesting that immunosuppression is a primary concordant featureof the disease, potentially arguing against the routine use of immunosuppressant medications. These data alsodemonstrate our ability to perform single cell RNA sequencing (scRNAseq), scATACseq, spectral flowcytometry, and ELISpot to evaluate gene expression, chromatin accessibility, protein expression, and immunecell function, respectively. With the consortium's approval to use residual IMPACC samples, these site-specificassays could be funded through outside mechanisms and the data shared across the IMPACC consortium.