Surveillance and identification of variants of concern within circulating SARS-CoV-2 across Kentucky

项目总结 导致新冠肺炎疾病的SARS-CoV-2病毒的出现和传播已导致4.64亿英镑 在短短两年多的时间里，全球感染和死亡人数超过600万人。全球测序工作已经确定 几种病毒变种的关注(VOC)和兴趣(VOI)，导致传播、毒力和疫苗的增加 逃逸，和/或增加了感染者的死亡率。进行病毒基因组监测是必要的，以确定 并确定病毒变种的特征，为正在进行的公共卫生努力和未来的疫苗/治疗设计提供信息 战略。这对机构发展奖(IDEA)州来说是特别迫切的需要，为此 对流行的SARS-CoV-2变种的了解相对有限。驱动SARS-CoV-2的机械力 多样化和变种的出现当然是多因素的。最近的报告表明，生物性行为和 年龄可能会影响免疫致病机制和个体韧性，而且地理上限制的循环和 变种的传播以及先前存在的社会脆弱性也可能影响SARS-CoV-2变种 动力学。有充分的记录表明，新冠肺炎对代表不足的人群产生了不成比例的影响， 包括黑人、土著和有色人种(BIPOC)和拉丁裔人。有关SARS-CoV-2的资料 在这些人群中的传播和变异体特征继续被低估。评估VOC如何像病毒一样 和VOI受到不同的遗传、生物和社会背景的影响将是提供 SARS-CoV-2的频率和特征的公平代表。环境监测工作 还开发了跟踪SARS-CoV-2在人口/社区层面的传播，提供最低限度的 低成本的侵入性、无偏VOC检测。临床监测数据与废水(WW)的整合 监测程序将丰富这两个数据集，为建模WW数据可能的最佳状态奠定基础 作为公共卫生当局的早期预警系统。尽管发展了多个稳健和 有效的疫苗，正在进行的病毒进化导致了对当前(和正在减弱的)疫苗水平的抗药性- 中介保护，这种模式很可能会在新兴的VOC中继续下去。使用强大的高吞吐量 和经济高效的单分子、实时测序方法，我们建议进行大规模的SARS- 来自肯塔基州(肯塔基州)的约6000份样本的CoV-2基因组监测显著改善了(1) 关于SARS-CoV-2动态和变异传播的数据可用性，调查生物学和 与挥发性有机化合物动态的地理关联，(2)污水和临床SARS-CoV-2监测的整合 数据，以及(3)识别与临床相关的SARS-CoV-2感染相关的突变特征。至 实现这一目标，我们已经建立了多机构的合作努力，发展了深层次的关键伙伴关系 学术、医疗保健、私人和公共卫生利益相关者网络，将该团队定位为病原体 正在进行和未来努力的监视中心。

PROJECT SUMMARY The emergence and circulation of SARS-CoV-2, the virus that causes COVID-19 disease, has led to >464 million infections and more than 6 million deaths worldwide in just over 2 years. Global sequencing efforts have identified several viral variants of concern (VOC) and interest (VOI) that result in increased transmission, virulence, vaccine escape, and/or increased mortality for those infected. Ongoing viral genomic surveillance is necessary to identify and characterize viral variants, to inform both ongoing public health efforts and future vaccine/treatment design strategies. This is a particularly urgent need for Institutional Development Award (IDeA) states, for which knowledge of circulating SARS-CoV-2 variants is relatively limited. The mechanistic forces driving SARS-CoV-2 diversification and variant emergence are certainly multifactorial. Recent reports suggest that biological sex and age may impact immunopathogenesis and individual resilience, and that geographically restricted circulation and transmission of variants, along with pre-existing social vulnerabilities may also impact SARS-CoV-2 variant dynamics. It is well documented that COVID-19 disproportionately impacts underrepresented populations, including Black, Indigenous and people of color (BIPOC) and Latinx peoples. Data regarding SARS-CoV-2 circulation and variant profiling in these populations continues to be underreported. Evaluating how viral VOC and VOI are impacted by differential genetic, biological and social backgrounds will be critical for providing equitable representation of the frequency and characteristics of SARS-CoV-2. Environmental surveillance efforts have also been developed to track SARS-CoV-2 spread at the population/community-level, providing minimally invasive, unbiased VOC detection at low cost. Integration of clinical surveillance data with wastewater (WW) monitoring programs will enrich both datasets, laying the groundwork for modeling how WW data may best be utilized as an early warning system for public health authorities. Despite the development of multiple robust and effective vaccines, ongoing viral evolution has resulted in resistance to current (and waning) levels of vaccine- mediated protection, and this pattern will likely continue with emerging VOCs. Using a robust, high throughput and cost-effective single molecule, real-time sequencing approach, we propose to perform large scale SARS- CoV-2 genomic surveillance from ~6000 samples sourced across Kentucky (KY) to (1) substantially improve data availability regarding SARS-CoV-2 dynamics and variant circulation, investigating biological and geographical association with VOC dynamics, (2) integrate wastewater and clinical SARS-CoV-2 surveillance data, and (3) identify mutational signatures associated with clinically relevant SARS-CoV-2 infections.. To achieve this, we have built a multi-institutional collaborative effort, developing key partnerships among a deep network of academic, healthcare, private and public health stakeholders, positioning this team as a pathogen surveillance center for ongoing and future efforts.