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型(SARS-CoV-2)病例 据报道，全世界已有新冠肺炎感染病例和250,000人死亡，病例超过120万例 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和 死亡。遗传因素似乎是SARS-CoV-2感染结果的一些个体间差异的基础。 这种遗传性的一部分可能与宿主免疫反应有关，就像医院里的淋巴细胞检测一样。 入院预测疾病的严重程度。同样重要的是，了解一个人的 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；多血统 淋巴细胞的多基因风险评分将进行测试，以预测新冠肺炎的严重程度以解决这一问题 假设。这一补充项目将改善1)电子健康记录表型的标准化 新冠肺炎的肺部和肾脏并发症，以提高跨站点移植；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。我们建议在目标范围内开展工作 通过开发可转移的EHR来研究新冠肺炎严重程度的个体差异 肺和肾脏结果的表型分型，评估ABO血型关联和GWAS对比 那些新冠肺炎呼吸衰竭患者(住院)与那些仍在门诊就诊的患者，并进行评估 淋巴细胞的多系PR是否能预测COVID的严重程度。这个项目可以独立运作，但 我们将通过跨Emerge汇聚数据获得力量，并通过在多个站点测试EHR表型来受益 确保可转让性。我们还将广泛共享任何数据。

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.