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.

项目概要 引起 COVID-19 疾病的病毒 SARS-CoV-2 的出现和传播已导致超过 1.25 亿人感染 短短一年多的时间里，全球就有超过 250 万人感染和死亡。全球测序工作已 确定了几种导致传播率增加的令人关注的病毒变种（VOC）和兴趣变种（VOI） 和/或感染新 SARS-CoV-2 毒株的人死亡率增加。尽管发展 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疫苗水平的耐药性 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 新的病毒变种，为正在进行的公共卫生工作和未来的疫苗设计策略提供信息。这是一个 特别迫切需要机构发展奖（IDeA）国家，因为传播知识 SARS-CoV-2 变异体极其有限。驱动 SARS-CoV-2 多样化的机制力量 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、具有广泛反应性的中和抗体 (nAb) 介导。最近开发的基因分型测定法 表征了免疫球蛋白 (IG) 位点内的广泛多样性，越来越多的证据表明 编码抗体库的基因组在不同种族人群中差异很大。而且， 最近的报告表明，生物性别可能会影响免疫发病机制和个体复原力，并且 变种的流通和传播受地理限制，以及预先存在的社会脆弱性 也可能影响 SARS-CoV-2 变异动态。有充分证据表明，COVID-19 对 代表性不足的人群，包括黑人、原住民和有色人种 (BIPOC) 以及拉丁裔。 有关这些人群中 SARS-CoV-2 传播和变异分析的数据也被低估 正在进行的病毒监测工作。评估病毒 VOC 和 VOI 如何受到差异遗传的影响， 生物和社会背景对于提供频率和频率的公平代表性至关重要 SARS-CoV-2 变体的特征，并作为生成机制假设的第一步 未来的研究。使用稳健、高通量且经济高效的单分子实时测序 方法，我们建议对约 7000 个样本进行大规模 SARS-CoV-2 基因组监测 肯塔基州 (KY) 的目标是 (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和社会相关性，(3) 杠杆作用 该管道旨在开发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、 和工业利益相关者，让该团队建立一个病原体监测中心，以进行持续和 未来的努力。