Pre-exposure Immunologic Health and Linkages to SARS-COV2 Serologic Responses, Endothelial Cell Resilience, and Cardiovascular Complications: Defining the mechanistic basis of high risk endotypes.

暴露前免疫健康及其与 SARS-COV2 血清学反应、内皮细胞弹性和心血管并发症的联系：定义高风险内型的机制基础。

• 批准号: 10706727
• 负责人: Timothy An-thy Chan
• 金额: $ 11.71万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706727
• 关键词: 2019-nCoV; ACE2; Acute; Adhesions; Affect; Angiotensin II; Antibody Response; Antigen Receptors; B-Cell Activation; Blood Tests; COVID-19; COVID-19 impact; COVID-19 mortality; COVID-19 pneumonia; COVID-19 risk; COVID-19 severity; COVID-19 survivors; Cardiac; Cardiac Myocytes; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Cathepsins; Cause of Death; Cells; Cessation of life; Chronic; Clinic; Clinical; Data; Deltastab; Disease; Distant; Down-Regulation; Economics; Endothelial Cells; Endothelium; Enrollment; Failure; Fibrosis; Foundations; Functional disorder; Future; Gene Expression; Gene Expression Profile; Genetic Transcription; Glucose; Goals; Health Personnel; Heart; Heart Diseases; Heart failure; Heterogeneity; Human; Immune; Immune System Diseases; Immunologics; Impairment; In Vitro; Individual; Infection; Infection prevention; Inflammation; Inflammatory; Integration Host Factors; Interleukin-6; Intervention; Knowledge; Left Ventricular Dysfunction; Life; Link; Lipoproteins; Longitudinal cohort; Lymphopenia; Magnetic Resonance; Maintenance; Malignant Neoplasms; Measures; Modeling; Molecular; Molecular Profiling; Morbidity - disease rate; Nature; Nodal; Organ; Outcome; Oxides; Pathway interactions; Patients; Permeability; Phenotype; Pilot Projects; Plasma; Play; Publishing; Recovery; Research; Risk; Risk Factors; Role; SARS-CoV-2 exposure; SARS-CoV-2 infection; SARS-CoV-2 pathogenesis; Scanning; Serology; Severities; Shapes; Stimulus; Survivors; Symptoms; T-Lymphocyte; T-Lymphocyte Subsets; TNF gene; Techniques; Testing; Tissues; Toxic effect; Ventricular Dysfunction; Viral; Viral Pneumonia; Virus; Work; adverse outcome; base; cardiometabolism; cardiovascular disorder risk; cohort; coronavirus disease; cytokine; cytokine release syndrome; cytotoxic; experimental study; gain of function; high risk; immune activation; immune function; immune health; immune system function; improved; international center; monocyte; mortality; multidisciplinary; neutralizing antibody; population health; prevent; prognostic; prospective; recruit; resilience; response; severe COVID-19; single cell sequencing; thrombotic; transcription factor; transcriptomics

We propose a two-year collaborative project to synchronize data harmonization efforts and analyses of individual-level data in immunocompromised populations to assess effectiveness of vaccine boosters and immune responses using data from 11 Serological Sciences Network (SeroNet) institutions. Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in these vulnerable populations. To do so requires large datasets of well-defined populations with clinical information and a robust collaborative infrastructure able to evolve as new research questions arise during the pandemic. Therefore, we propose to mimic the NA-ACCORD strategy of pooling cohorts at multiple sites in North America (https://naaccord.org). The foundational work of the NA-ACCORD enabled them to rapidly pivot to establish the CIVET-II cohort collaboration during the pandemic. To be time- and cost-efficient, we propose a single pooling project that merges data from both (i) electronic medical records as well as (ii) prospective cohorts from SeroNet sites across the U.S. The cooperation of many SeroNet sites is crucial and will allow results to be more generalizable to the wider U.S. population, including investigation of sources of heterogeneity (e.g., age, sex, race/ethnicity and geography). Data harmonization efforts will be streamlined, and analyses will be divided by research area across all sites to allow multiple publications to occur simultaneously.

我们提出了一个为期两年的合作项目，同步数据协调工作和分析免疫功能低下人群的个人水平的数据，以评估疫苗助推器和免疫反应的有效性，使用来自11个血清学科学网络（SeroNet）机构的数据。我们的目标是为COVID-19疫苗和加强剂的公共卫生指南提供信息，以减少这些脆弱人群的SARS-CoV-2感染和严重疾病。要做到这一点，就需要有明确定义的人群的大型数据集，其中包括临床信息和强大的协作基础设施，这些基础设施能够在大流行期间随着新的研究问题的出现而发展。因此，我们建议模拟北美多个研究中心的NA-ACCORD合并队列策略（https：naaccord.org）。NA-ACCORD的基础工作使他们能够在大流行期间迅速建立CIVET-II队列合作。为了节省时间和成本，我们提出了一个单一的合并项目，该项目合并了来自（i）电子病历以及（ii）来自美国各地SeroNet站点的前瞻性队列的数据。许多SeroNet站点的合作至关重要，将使结果更适用于更广泛的美国人群，包括异质性来源的调查（例如，年龄、性别、种族/民族和地域）。数据协调工作将得到简化，分析将按研究领域在所有研究中心进行划分，以便同时发表多篇文章。