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

摘要 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25万例感染（COVID-19）和25万例死亡，超过120万例及以上 美国有7万人死亡。感染的严重程度从没有症状到呼吸衰竭， 死亡遗传因素似乎是SARS-CoV-2感染结果中某些个体间差异的基础。 这种遗传性的一部分可能与宿主的免疫反应有关，如在医院的淋巴细胞测量 入院可预测疾病严重程度。了解一个人的 基础或“基线”淋巴细胞计数是感染和/或严重疾病的风险因素;多血统 将测试淋巴细胞多基因风险评分对COVID-19严重程度的预测，以解决这一问题 假说.该补充项目将提高1）电子健康记录表型的标准化， COVID-19的肺部和肾脏并发症，以提高跨站点的可转移性;以及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。我们建议在以下目标范围内开展工作： eMERGE 4通过开发可转移的EHR来研究COVID-19严重程度的个体间变异性 肺和肾结局的表型分析，评估ABO血型相关性和GWAS对比 COVID-19呼吸衰竭患者（住院患者）和门诊患者，并评估 淋巴细胞的多血统PRS是否可预测COVID的严重程度。这个项目可以独立存在，但 我们将通过在eMERGE中汇集数据来获得力量，并通过在多个站点测试EHR表型来获益， 确保可转移性。我们还将广泛分享任何数据。

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.