Coord Core - Atkinson

坐标核心 - 阿特金森

• 批准号: 10254841
• 负责人: MARK A. ATKINSON
• 金额: $ 135.15万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254841
• 关键词: 2019-nCoV; 3-Dimensional; Acute; Acute Disease; Address; Adult; Annual Reports; Antibodies; Aspirate substance; Asthma; Autoimmune Diseases; Biological Assay; Biological Markers; Blood; COVID-19; COVID-19 pandemic; Cell physiology; Chromatin; Clinical Research; Cohort Studies; Collection; Communication; Communication Programs; Communities; Consent; Core Facility; Data; Data Collection; Data Protection; Data Set; Database Management Systems; Databases; Development; Disease; Elements; Emerging Technologies; Enrollment; Ensure; Evaluation; Feedback; Florida; Flow Cytometry; Foundations; Funding; Gene Expression; General Hospitals; Generations; Genetic; Genotype; Goals; Grant; Health; Health Sciences; Healthcare; Hospitalization; Hospitals; Human; Human BioMolecular Atlas Program; Hypersensitivity; Immune; Immune response; Immune system; Immunity; Immunologics; Immunophenotyping; Immunosuppression; Immunosuppressive Agents; Individual; Infection; Infrastructure; Institutional Review Boards; Insulin-Dependent Diabetes Mellitus; Intubation; Laboratories; Leadership; Link; Lymph; Lymphatic System; Lymphocyte; Malignant Neoplasms; Measurement; Mediating; Medical History; Medical center; Metabolic; Mission; Monitor; National Institute of Allergy and Infectious Disease; Newsletter; Nose; Observational Study; Online Systems; Operations Research; Organ; Organ Donations; Organ Procurements; Outcome; Outpatients; Participant; Pathogenesis; Patients; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Physiological; Physiology; Process; Program Reviews; Progress Reports; Prospective cohort; Proteomics; Public Health; Publications; Race; Recommendation; Recording of previous events; Recovery; Research; Research Personnel; Residual state; Resource Allocation; Resources; Role; Sampling; Schedule; Scheme; Services; Severity of illness; Ships; Site; Spleen; Structure; Survivors; Swab; Therapeutic Intervention; Thrombosis; Thymus Gland; TimeLine; Tissues; Training; Trust; United States National Institutes of Health; Universities; University Hospitals; Viral; Viral Load result; Virus; Visit; Work; Writing; cohort; combat; coronavirus disease; cytokine release syndrome; data sharing; design; endotracheal; experience; improved; knowledge of results; laboratory facility; longitudinal analysis; lymph nodes; meetings; member; metabolomics; mortality; new therapeutic target; organ growth; pathogen; peripheral blood; precision medicine; programs; prospective; protein expression; recruit; research study; sample collection; sex; single-cell RNA sequencing; success; symposium; targeted treatment; webinar

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.

迫切需要广泛的临床研究来告知患者管理策略并制定 对抗 2019 年新型冠状病毒病（COVID-19）的药物对策。现在， 佛罗里达州的 COVID-19 感染和住院人数激增；因此，我们建议 建立佛罗里达大学 (UF) 作为受试者注册和样本收集中心 佛罗里达州三个健康科学机构开展的 COVID-19 队列 (IMPACC) 研究中的免疫表型评估 中心。在这项全国性的前瞻性观察研究中，外周血和鼻拭子将经常被 从经同意的确诊 COVID-19 住院患者中收集，还进行气管内抽吸 如果患者需要插管则收集。参与者出院后，将采集血液和鼻拭子 一年内每三个月一次的门诊就诊期间收集的数据， 纵向分析病毒在感染期间和感染后对免疫系统的影响 恢复。通过 OneFlorida 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，以支持参与者同意/注册和样本收集 作为样品处理的现场实验室设施。在目标 1 中，我们建议整合三个 OneFlorida CRC 收集地点（坦帕综合医院/南佛罗里达大学、佛罗里达大学健康杰克逊维尔医疗中心、 和位于盖恩斯维尔的 UF Health Shands 医院）参与 IMPACC 研究。这些网站有足够的 COVID-19 在四个月的招募期内支持 100 名参与者注册的案件量。瞄准 2、样品采集后立即处理并运送至六大核心实验室进行精密检测 医学基因分型、病毒测序、蛋白质组学/代谢组学、抗体测量和同种型分析等 以及 CyTOF 免疫表型分析。从这些集体数据中，IMPACC 试图将病毒负荷与 免疫特征作为急性疾病严重程度、死亡率、持久免疫力发展的生物标志物， 以及幸存者的长期结果。此外，广泛的免疫表型数据有可能 发现新的治疗靶点以减轻疾病的严重程度。最初，COVID-19 死亡率归因于 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 患有严重疾病。然而，为了支持免疫表型分析的力量，提供关键 信息，我们提供初步数据表明免疫抑制是主要一致特征 该疾病，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 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 分别是细胞功能。经该联盟批准使用剩余的 IMPACC 样本后，这些特定地点 分析可以通过外部机制和 IMPACC 联盟共享的数据来资助。