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征引起的2019冠状病毒病（COVID-19）大流行 冠状病毒-2（SARS-CoV-2）已导致全球超过500万人死亡。作为大流行病的负担， 在美国（US）从城市转移到农村社区，初步研究表明，农村人口 他们的疾病严重程度和死亡率高于城市人口。然而，即使20%的 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 由于人口众多，大多数COVID-19研究主要集中在大型城市中心， 农村社区的缓解努力主要参考以城市为中心的数据。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， 城市和农村地区之间的疾病相互作用。然而，有限的临床和基因组数据，特别是 来自农村地区的病毒，使我们无法充分了解COVID-19的疾病动态。 这项培训补助金的目的是确定SARS-CoV-2变异如何出现和传播， 城市和农村社区，并确定与临床相关的病毒，宿主和人口因素 成果，同时培训先进的生物信息学方法，转化研究设计， 和计算思维，成为一名独立的医生科学家。中心假设是， SARS-CoV-2变异出现在城市中心并传播到农村环境， 病毒、宿主和人口因素与疾病严重程度有关。为了验证我们的假设， 目的是确定SARS-CoV-2变异体在城市人群中的遗传多样性和传播， 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 (Aim 2）。现有和正在进行的多年数据集，包括临床信息和全基因组 将使用来自密苏里州城市和农村地区的COVID-19阳性样本进行测序 在这两个目标。 本提案是为了响应NIAID COVID-19研究优先事项1的战略计划而提交的， “评估新出现的SARS-CoV-2变异的功能后果。我们期待由此产生的结果 我们的研究将从两个方面支持这一优先事项：1）我们将确定SARS-CoV-2变体的传播模式 城市和农村社区之间，2）我们将确定现有和新兴的临床意义 SARS-CoV-2变异体，因为它们与各种其他病毒和宿主因子相互作用。该项目的成果将 提高对SARS-CoV-2传播动态和临床影响的认识，特别是在农村地区 这对缓解COVID-19和未来的大流行病至关重要。

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.