Coord Core - Atkinson

迫切需要进行广泛的临床研究，以便为患者的管理策略提供信息并制定 抗击2019年新型冠状病毒病(新冠肺炎)的药物对策。目前， 新冠肺炎感染和住院人数在佛罗里达州激增；因此，我们建议 建立佛罗里达大学(UF)作为学科-招生和样本收集中心 佛罗里达三所健康科学中心新冠肺炎队列研究中的免疫表型评估 中锋。在这项全国性的前瞻性观察研究中，外周血和鼻拭子将频繁 收集自同意住院的确诊为新冠肺炎的患者，也有气管内吸入物 如果患者需要插管，则收集。参与者出院后，血液和鼻拭子将 在一年中每隔三个月进行一次门诊访问期间收集的数据，允许 活动性感染和后续感染时病毒对免疫系统影响的纵向分析 恢复。通过佛罗里达州临床研究联盟(CRC)，我们已经建立了 基础设施，包括训练有素的工作人员，以支持参与者的同意/登记和样本收集 作为现场实验室的样品处理设施。在目标1中，我们建议整合三个One佛罗里达儿童权利公约 收集地点(坦帕综合医院/南佛罗里达大学，UF Health Jacksonville医疗中心， 和盖恩斯维尔的UF健康斯汉兹医院)进入IMPACC研究。这些网站有足够的新冠肺炎 在为期四个月的招聘期内支持100名参与者参加的工作量。在AIM 2、样品在采集后立即进行处理，并运往六个核心实验室进行精密度检测 药物基因分型、病毒测序、蛋白质组学/代谢组学、抗体测定和同位素分型，AS 细胞免疫表型分析。从这些收集的数据中，IMPACC试图将病毒负担与 作为急性疾病严重程度、死亡率、持久免疫发展的生物标志物的免疫信号， 以及幸存者的长期结果。此外，大量的免疫表型数据有可能 发现新的治疗目标以减轻疾病的严重性。最初，新冠肺炎的死亡被归因于 细胞因子风暴和血栓形成增强，支持患者使用免疫抑制药物治疗 身患重病。然而，为了努力支持免疫表型的威力，提供了关键 信息，我们提供的初步数据表明免疫抑制是一个主要的一致性特征。 这可能会反对常规使用免疫抑制药物。这些数据还 展示我们执行单细胞RNA测序(ScRNAseq)、scATACseq、光谱流的能力 流式细胞术和ELISpot评估基因表达、染色质可及性、蛋白质表达和免疫 细胞功能。在财团批准使用剩余的IMPACC样本后，这些特定于现场的样本 检测可以通过外部机制和IMPACC财团共享的数据提供资金。

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.