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1.25亿英镑 在短短一年多的时间里，全球感染和死亡人数超过250万人。全球测序工作已经完成 确定了导致传播率增加的几种病毒变种关注(VOC)和兴趣(VOI) 和/或增加了感染新的SARS-CoV-2毒株的人的死亡率。尽管……的发展 多种强大而有效的疫苗，进一步的病毒进化可能会导致对当前水平的疫苗产生抗药性- 中介保护。进行病毒基因组监测是必要的，以识别和表征已知和 新的病毒变种，为正在进行的公共卫生努力和未来的疫苗设计战略提供信息。这是一个 特别迫切需要机构发展奖(IDEA)的国家，为其知识的流传 SARS-CoV-2变种极其有限。推动SARS-CoV-2病毒多样化和 变异的出现当然是多因素的。有效的天然和疫苗抗病毒保护被认为是 由有效的、广泛反应的中和抗体(NAB)介导。最近发展起来的基因分型分析已经 描述了免疫球蛋白(IG)基因座的广泛多样性，越来越多的证据表明 编码抗体库的基因集体阵列在不同种族人群中差异很大。此外， 最近的报告表明，生物性行为可能会影响免疫病理机制和个人韧性，而且 变种在地理上的流通和传播受到限制，以及先前存在的社会脆弱性 也可能影响SARS-CoV-2变异动态。有充分的证据表明，新冠肺炎对 代表性不足的人群，包括黑人、土著和有色人种(BIPOC)和拉丁裔人。 关于SARS-CoV-2在这些人群中传播和变异特征的数据在#年也被低估了 正在进行的病毒监测工作。评估差异遗传对病毒VOC和VOI的影响， 生物和社会背景将对提供公平的频率和 SARS-CoV-2变异株的特征，并作为迈向机制假说生成的第一步 未来的研究。使用强大、高通量和经济高效的单分子、实时测序 方法，我们建议从7000个样本中进行大规模SARS-CoV-2基因组监测 从肯塔基州(肯塔基州)到(1)大幅提高有关SARS-CoV-2动态和变异的数据可用性 循环，(2)评估变异出现和进化的生物学和社会相关性，以及(3)杠杆作用 这条管道将开发一门独特的病原体监测课程。为了实现这一目标，我们建立了一个多 机构协作努力，在学术、医疗保健、 和行业利益相关者，将该团队定位为建立一个病原体监测中心，以持续和 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 >125 million infections and more than 2.5 million deaths worldwide in just over 1 year. Global sequencing efforts have identified several viral variants of concern (VOC) and interest (VOI) that result in increased transmission rates and/or increased mortality for those infected with the new SARS-CoV-2 strains. Despite the development of multiple robust and effective vaccines, further viral evolution may result in resistance to current levels of vaccine- mediated protection. Ongoing viral genomic surveillance is necessary to identify and characterize known and new viral variants, to inform both ongoing public health efforts, and future vaccine design strategies. This is a particularly urgent need for Institutional Development Award (IDeA) states, for which knowledge of circulating SARS-CoV-2 variants is extremely limited. The mechanistic forces driving SARS-CoV-2 diversification and variant emergence are certainly multifactorial. Effective natural and vaccine antiviral protection is thought to be mediated by potent, broadly reactive neutralizing antibodies (nAbs). Recently developed genotyping assays have characterized the extensive diversity within immunoglobulin (IG) loci, with increasing evidence suggesting that the collective array of genes that encode antibody repertories differ widely across ethnic populations. Moreover, recent reports suggest that biological sex 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 in also underreported in ongoing viral surveillance efforts. 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 variants, and act as a first step towards mechanistic hypothesis generation for future studies. 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 ~7000 samples sourced across Kentucky (KY) to (1) substantially improve data availability regarding SARS-CoV-2 dynamics and variant circulation, (2) evaluate biological and social correlates of variant emergence and evolution, and (3) leverage this pipeline to develop a unique curriculum in pathogen surveillance. To achieve this, we have built a multi- institutional collaborative effort, developing key partnerships among a deep network of academic, healthcare, and industrial stakeholders, positioning this team to establish a pathogen surveillance center for ongoing and future efforts.