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

肯塔基州流行的 SARS-CoV-2 中值得关注的变种的监测和鉴定

• 批准号: 10381183
• 负责人: Jason A. Chesney
• 金额: $ 77.84万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10381183
• 关键词: 2019-nCoV; Address; Age; Antibodies; Antiviral Agents; Award; Biological; Biological Assay; Black, Indigenous, People of Color; Blood Circulation; Brazil; COVID-19; COVID-19 severity; COVID-19 surveillance; Cessation of life; Characteristics; Collaborations; Color; Communicable Diseases; Communities; Complement; Country; County; Custom; Data; Data Set; Databases; Deposition; Detection; Development; Diagnostic; Disease; Educational Curriculum; Ensure; Ethnic Origin; Ethnic group; Etiology; Evolution; Female; Frequencies; Future; Future Generations; Genes; Genetic; Genomics; Genotype; Geographic Locations; Geography; Government Agencies; Health Care Research; Healthcare; Immune response; Immunoglobulins; Individual; Industrialization; Infection; Informatics; Institution; Kentucky; Knowledge; Laboratories; Latinx; Mediating; Methods; Mutation; Outcome Study; Pathogenicity; Phylogenetic Analysis; Population; Positioning Attribute; Privatization; Public Health; RNA; Race; Reporting; Resistance; SARS-CoV-2 genome; SARS-CoV-2 infection; SARS-CoV-2 variant; Sampling; Secure; Source; South Africa; Specimen; Surveillance Program; Time; Training; Underrepresented Populations; United Kingdom; Universities; Vaccine Design; Vaccines; Variant; Viral; Viral Genome; Viral Pathogenesis; Virus; base; biological sex; cost effective; design; driving force; genomic signature; graduate student; health inequalities; improved; infection rate; informatics tool; interest; male; molecular sequence database; mortality; neutralizing antibody; next generation; novel; pandemic disease; pathogen; population based; prospective; resilience; single molecule real time sequencing; skills; social; social vulnerability; surveillance data; transmission process; undergraduate student; variants of concern; viral genomics; viral transmission

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.

项目摘要 SARS-COV-2的出现和循环是导致Covid-19疾病的病毒，已导致了1.25亿 在仅1年以上的全球感染和超过250万人的死亡。全球测序工作有 确定了几种关注的病毒变异（VOC）和兴趣（VOI），导致传输率提高 和/或感染新的SARS-COV-2菌株的人的死亡率增加。尽管发展了 多种可靠且有效的疫苗，进一步的病毒进化可能会导致对当前疫苗水平的抗性 - 介导的保护。持续的病毒基因组监测对于识别和表征已知和特征是必要的 新的病毒变体，以告知正在进行的公共卫生工作以及未来的疫苗设计策略。这是一个 特别迫切需要机构发展奖（IDEA）国家，以了解循环的知识 SARS-COV-2变体非常有限。驱动SARS-COV-2多样化的机械力和 变体出现无疑是多因素。有效的天然和疫苗抗病毒保护被认为是 通过有效的，广泛反应性的中和抗体（NABS）介导。最近开发的基因分型分析有 表征了免疫球蛋白（IG）基因座中广泛的多样性，越来越多的证据表明 编码抗体库库的集体基因在种族种群之间差异很大。而且， 最近的报道表明，生物学可能会影响免疫发育生成和个人韧性，并且 在地理上受到限制的变体的循环和传播，以及现有的社会脆弱性 还可能影响SARS-COV-2变体动力学。有充分的文献证明，共vid-19不成比例地影响 代表性不足的人群，包括黑人，土著人和有色人种（BIPOC）和拉丁人。 这些人群中有关SARS-COV-2循环和变体分析的数据也不足 正在进行的病毒监测工作。评估病毒性VOC和VOI如何受到差异遗传的影响， 生物学和社会背景对于提供频率和公平表示频率至关重要 SARS-COV-2变体的特征，并作为迈向机械假设产生的第一步 未来的研究。使用健壮的高吞吐量和具有成本效益的单分子，实时测序 方法，我们建议从〜7000个样本中执行大规模SARS-COV-2基因组监视 跨肯塔基州（KY）到（1）实质上改善了有关SARS-COV-2动力学和变体的数据可用性 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 该管道在病原体监测中开发独特的课程。为了实现这一目标，我们已经建立了 机构合作的努力，建立了重要的学术，医疗保健网络之间的关键伙伴关系， 和工业利益相关者，将这个团队定位为建立一个正在进行和的病原体监视中心 未来的努力。