Evolution, transmission, and clinical impacts of SARS-CoV-2 variants among urban and rural populations

项目摘要 由严重急性呼吸系统综合症引起的2019年冠状病毒病(新冠肺炎)大流行 冠状病毒-2(SARS-CoV-2)已导致全世界500多万人死亡。作为大流行的负担 在美国，从城市社区向农村社区的转变，初步研究表明，农村人口 比城市人口遭受更高的疾病严重程度和死亡率。然而，即使20%的人 美国人口生活在农村地区，农村人口具有与城市不同的已知风险因素 在人群方面，大多数新冠肺炎研究主要集中在大城市中心和疾病 农村社区的缓解工作很大程度上是由以城市为中心的数据提供信息的。因此，迫切需要 了解SARS-CoV-2变异株在农村地区的演变、传播和临床影响 城乡之间疾病的相互作用。然而，有限的临床和基因组数据，特别是 来自农村地区的疾病，使我们无法充分了解新冠肺炎的疾病动态。 这项培训赠款的目的是确定SARS-CoV-2变种是如何出现并在 并确定与临床相关的病毒、宿主和人口因素 在高级生物信息学方法、转化性研究设计、 和计算思维成为一名独立的内科科学家。中心假设是 SARS-CoV-2变种出现在城市中心并传播到农村环境，一套协同的 病毒、宿主和人口因素与疾病严重程度有关。为了检验我们的假设，有两个具体的例子 目的是确定SARS-CoV-2变异株的遗传多样性和在城市中的传播 和农村地区(目标1)，并模拟宿主、SARS-CoV-2病毒和人口因素的临床影响 (目标2)。现有的和正在进行的多年数据集，包括临床信息和全基因组 密苏里州城乡地区新冠肺炎阳性个体样本的测序将被使用 在这两个目标上。 本提案是为响应国家发改委的《新冠肺炎研究重点1战略规划》而提出的。 “评估新出现的SARS-CoV-2变种的功能后果。”我们期待着由此产生的结果 通过两种方式支持这一优先事项的研究：1)我们将确定SARS-CoV-2变种的传播模式 城市和农村社区之间，以及2)我们将确定现有的和新出现的 SARS-CoV-2变种与各种其他病毒和宿主因素相互作用。这个项目的结果将是 提高对SARS-CoV-2传播动态和临床影响的了解，特别是在农村地区 这对于缓解新冠肺炎和未来的流行病将是重要的。

Project Summary The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in over 5 million deaths worldwide. As the burdens of the pandemic in the United States (US) shift from urban to rural communities, preliminary studies suggest that rural populations suffer from higher disease severity and mortality rates than urban populations. However, even while 20% of the US population lives in a rural area and rural populations have known risk factors that differ from urban populations, the majority of COVID-19 research has primarily focused on large urban centers, and disease mitigation efforts in rural communities are largely informed by urban-centric data. Thus, it is urgently necessary to understand the evolution, spread, and clinical impacts of SARS-CoV-2 variants in rural areas and the disease interactions among urban and rural regions. However, limited clinical and genomic data, particularly from rural areas, are available, preventing us from fully understanding the disease dynamics of COVID-19. The objectives of this training grant are to determine how SARS-CoV-2 variants emerge and spread among urban and rural communities and to determine the virus, host, and population factors associated with clinical outcomes while training an MD-PhD student in advanced bioinformatics approaches, translational study design, and computational thinking to become an independent physician scientist. The Central Hypotheses are that SARS-CoV-2 variants arise in urban centers and spread into rural environments and that a synergistic set of virus, host, and population factors are associated with disease severity. To test our hypotheses, two specific aims are proposed to determine the genetic diversity and spread of SARS-CoV-2 variants among urban and rural regions (Aim 1) and to model clinical impacts of host, SARS-CoV-2 virus, and population factors (Aim 2). An existing and ongoing multi-year dataset that includes clinical information and whole genome sequencing of COVID-19-positive samples of individuals from urban and rural regions of Missouri will be used in both aims. This proposal is submitted in response to the NIAID Strategic Plan for COVID-19 Research Priority 1, “Assess functional consequences of newly emerging SARS-CoV-2 variants.” We expect the results from this study to support this priority in two ways: 1) We will determine the transmission patterns of SARS-CoV-2 variants between urban and rural communities, and 2) We will determine the clinical implications of existing and emerging SARS-CoV-2 variants as they interact with various other virus and host factors. The results from this project will improve the understanding of SARS-CoV-2 transmission dynamics and clinical impacts, particularly among rural populations, which will be important for the mitigation of COVID-19 and future pandemics.