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

项目摘要 导致COVID-19疾病的SARS-CoV-2病毒的出现和传播已导致超过4.64亿人死亡， 感染和超过600万人死亡，在短短两年多的时间里。全球测序工作已经确定 几种引起关注的病毒变体（VOC）和感兴趣的病毒变体（VOI），导致传播、毒力、疫苗 逃逸和/或增加感染者的死亡率。持续的病毒基因组监测对于识别 并描述病毒变异，为正在进行的公共卫生工作和未来的疫苗/治疗设计提供信息 战略布局这是一个特别迫切需要机构发展奖（IDEA）的国家， 对传播的SARS-CoV-2变异体的了解相对有限。驱动SARS-CoV-2的机械力 多样化和变异的出现当然是多因素的。最近的报告表明，生物性别和 年龄可能会影响免疫发病机制和个体的恢复力，地理上限制的循环和 变异的传播，沿着预先存在的社会脆弱性也可能影响SARS-CoV-2变异 动力学有充分的证据表明，COVID-19对代表性不足的人群造成了不成比例的影响， 包括黑人、土著人和有色人种（BIPOC）以及拉丁人。关于SARS-CoV-2的数据 这些人群中的流行和变异特征分析仍然报告不足。评估病毒性VOC如何 和VOI受到不同的遗传，生物和社会背景的影响， SARS-CoV-2的频率和特征的公平代表性。环境监测工作 还开发了用于跟踪SARS-CoV-2在人群/社区水平的传播， 以低成本进行侵入性、无偏VOC检测。临床监测数据与废水的整合（WW） 监测计划将丰富这两个数据集，为建模WW数据如何最好地 作为公共卫生当局的早期预警系统。尽管发展了多种强大的和 有效的疫苗，正在进行的病毒进化导致了对当前（和减弱）疫苗水平的抵抗， 介导的保护，并且这种模式可能会随着新出现的挥发性有机化合物而持续下去。使用强大的高吞吐量 和具有成本效益的单分子，实时测序方法，我们建议进行大规模的SARS- 来自肯塔基州（KY）约6000份样本的CoV-2基因组监测（1）显著改善 关于SARS-CoV-2动态和变异循环的数据可用性，调查生物学和 与VOC动态的地理关联，（2）整合废水和临床SARS-CoV-2监测 数据，和（3）识别与临床相关的SARS-CoV-2感染相关的突变特征。到 为了实现这一目标，我们建立了多机构的合作努力，在一个深入的 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 监控中心的持续和未来的努力。

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.