eMERGE SARS-CoV-2 Supplement: Pulmonary, renal, and inflammatory components

eMERGE SARS-CoV-2 补充剂：肺、肾和炎症成分

基本信息

批准号：
10164629
负责人：
David Russell Crosslin
金额：
$ 37.52万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-11 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10164629
关键词：
2019-nCoV ABO blood group system Abdominal Pain Acute Acute respiratory failure Address Administrative Supplement Adult Adult Respiratory Distress Syndrome Affect Anosmia Basophils Blood Cells COVID-19 Cardiovascular system Caring Case Series Centers for Disease Control and Prevention (U.S.)Cessation of life Chest Chronic Clinical Trials Clinical effectiveness Collaborations Coughing Critical Care Critical Illness Dangerousness Data Data Pooling Development Diagnosis Diarrhea Disease Elderly Electronic Health Record Evaluation Fatigue Fever Funding General Hospitals Genetic Genetic Predisposition to Disease Genetic study Genotype Headache Health Hematology Heritability Hospitalization Human Image Immune response Individual Infection Inflammatory Injury to Kidney Inpatients Institutes Intensive Care Intensive Care Units Interleukin-6 Kidney Leukocytes Lung Lung diseases Lymphocyte Lymphocyte Count Lymphopenia Measures Modeling Myalgia Outcome Outpatients Participant Pathway interactions Patients Persons Phenotype Play Pneumonia Prevention strategy Recovery Reporting Respiratory Failure Risk Factors Role Severities Severity of illness Shortness of Breath Site Sore Throat Standardization Symptoms Testing Thrombosis Time Twin Multiple Birth United States Universities Validation Variant Viral Washington Work clinically relevant cohort comorbidity coronavirus disease cytokine design early childhood eosinophil genetic analysis genetic risk factor genome wide association study improved infancy male monocyte mortality myocardial injury phenotyping algorithm polygenic risk score treatment strategy

项目摘要

Abstract As of May 4, 2020, more than 3.5M cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and 250,000 deaths have been reported worldwide, with more than 1.2M cases and over 70,000 deaths in the United States. The severity of infection varies from no symptoms to respiratory failure and death. Genetic factors appear to underlie some interindividual variability in SARS-CoV-2 infection outcomes. Part of this heritability may be associated with host immune response, as lymphocyte measures at hospital admission predict disease severity. It may be may also be important to understand whether an individual's underlying or “baseline” lymphocyte count is a risk factor for infection and/or severe disease; a multiancestry polygenic risk score for lymphocytes will be tested for its prediction of COVID-19 severity to address this hypothesis. This supplemental project will improve 1) standardization of electronic health record phenotyping of the pulmonary and renal complications of COVID-19 to improve transferability across sites; and 2) our understanding of host genetic risk factors playing a role in disease severity. We propose to work within the aims of eMERGE4 to study interindividual variability in COVID-19 severity by developing transferable EHR phenotyping of pulmonary and renal outcomes, evaluating ABO blood group association and GWAS contrasting those COVID-19 patients with respiratory failure (inpatient) with those who remained outpatients, and evaluating whether a multi-ancestry PRS for lymphocytes predicts COVID severity. This project can stand on its own, but we will gain power by pooling data across eMERGE and benefit by testing EHR phenotyping at multiple sites to assure transferability. We will also broadly share any data.

抽象的截至 2020 年 5 月 4 日，超过 350 万例严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 全球已报告感染 (COVID-19) 和 250,000 例死亡，病例超过 120 万例及以上美国有 70,000 人死亡，感染的严重程度从无症状到呼吸衰竭不等。遗传因素似乎是 SARS-CoV-2 感染结果存在一定个体差异的原因。这种遗传性部分可能与宿主免疫反应有关，如医院的淋巴细胞测量入院预测疾病的严重程度可能也很重要。潜在或“基线”淋巴细胞计数是感染和/或严重疾病的危险因素；将测试淋巴细胞的多基因风险评分，以预测其对 COVID-19 严重程度的预测，以解决这一问题该补充项目将改进 1) 电子健康记录表型的标准化。 COVID-19 的肺部和肾脏并发症，以提高跨地点的可转移性；2) 我们的了解宿主遗传风险因素在疾病严重程度中的作用，我们建议在这些目标范围内开展工作。 eMERGE4 通过开发可转移的 EHR 来研究 COVID-19 严重程度的个体差异肺和肾结果的表型分析、评估 ABO 血型关联和 GWAS 对比那些患有呼吸衰竭（住院）的 COVID-19 患者与仍在门诊的患者，并评估淋巴细胞的多祖先 PRS 是否可以预测新冠肺炎的严重程度这个项目可以独立存在，但是。我们将通过在 eMERGE 上汇集数据来获得力量，并通过在多个站点测试 EHR 表型来受益确保可转移性。我们还将广泛共享任何数据。