SARS-CoV-2 whole genome sequencing from large-scale campus testing and state-wide communities in NH

项目总结/摘要 SARS-CoV-2大流行给全球公共卫生系统带来了挑战。令人关切的几个变体 其中一些增加了疾病的传播性、严重程度、再感染的风险，和/或 对既往感染或疫苗接种的反应不同。在美国，特别是在新罕布什尔州， 的SARS-CoV-2基因组测序已经稀疏，但已经大大增加了我们的先前 努力此外，SARS-CoV-2测序工作主要针对有症状的 个人和/或特殊病例的接触者追踪。我们目前在几个方面缺乏知识：（1） 区域社区中SARS-CoV-2变异体出现的时间顺序和地理位置;（2） 传播性增加与SARS-CoV-2变异之间的相关性;（3） 不同人种、种族、性别和年龄组之间的变异分布以及 临床症状;和（4）先前感染和/或接种疫苗的个体获得 病毒以及哪些变种正在重新感染这些个体。此外，SARS-CoV-2废水监测 是一个有价值的公共卫生工具，但我们缺乏对SARS-CoV-2之间关系的了解， 人类样本中的变异和来自同一地理位置的废水样本中检测到的变异。 主要目标是继续确定一个大的，有代表性的一组基因组序列。 在NH状态下的SARS-CoV-2变异，并应用这些知识更好地了解 特定的变异增加了病毒的传播性，逃避了先前感染者的免疫系统， 感染，或增加感染个体经历临床症状的可能性。我们的中央 假设SARS-CoV-2变异体全基因组序列分析将显示出显著差异 在时间和地理位置流行率方面， 症状，以及感染免疫系统先前受到挑战的个体的能力。 我们将对约5000份存档和前瞻性收集的SARS-CoV-2诊断标本进行测序， 来自新罕布什尔州大学、新罕布什尔州卫生和人类健康部的检测呈阳性的个人 服务，以及达特茅斯学院和达特茅斯的COVID-19监测和临床测试项目- 希区柯克医疗中心。此外，我们将评估基因组监测废水的能力 样本作为SARS-CoV-2爆发的前哨，在一个聚集的社区， 可以在来自相同地理位置的废水样品和人类样本之间进行相关性。 了解SARS-CoV-2变异体的分布和传染性将使公共卫生机构能够 就需要颁布的公共卫生措施提供更准确和具体的指导， COVID-19基于特定人群中存在的SARS-CoV-2变异类型。

PROJECT SUMMARY/ABSTRACT The SARS-CoV-2 pandemic has challenged public health systems globally. Several variants of concern have been identified, some of which increase transmissibility, severity of disease, risk for reinfection, and/or variable responses to prior infection or vaccination. In the US—and especially in New Hampshire—the number of SARS-CoV-2 genomes sequenced has been sparse but have been substantially increased by our prior efforts. Furthermore, SARS-CoV-2 sequencing efforts have primarily been directed toward symptomatic individuals and/or contact tracing of special cases. We currently lack knowledge in several areas: (1) the temporal sequence and geolocation of the appearance of SARS-CoV-2 variants in regional communities; (2) the correlation between increases in transmissibility and SARS-CoV-2 variants; (3) differences in the distribution of variants among different racial, ethnic, gender, and age groups as well as in presentation of clinical symptoms; and (4) the extent to which previously infected and/or vaccinated individuals acquire the virus and which variants are reinfecting these individuals. In addition, wastewater surveillance of SARS-CoV-2 is a valuable public health tool but we lack an understanding of the relationship between the SARS-CoV-2 variants in human specimens and the variants detected in wastewater samples from the same geolocation. The primary objective is to continue determining the genomic sequence of a large, representative set of SARS-CoV-2 variants within the state of NH and to apply this knowledge to better understand the likelihood that specific variants increase transmissibility of the virus, evade the immune systems of those previously infected, or increase the likelihood of infected individuals to experience clinical symptoms. Our central hypothesis is that whole genome sequence analysis of SARS-CoV-2 variants will exhibit significant differences in temporal and geolocation prevalence, susceptibility of sub-populations to become infected and develop symptoms, and ability to infect individuals whose immune systems have previously been challenged. We will sequence ~5000 archived and prospectively collected SARS-CoV-2 diagnostic specimens from individuals who test positive from the University of New Hampshire, the NH Department of Health and Human Services, and the COVID-19 surveillance and clinical testing programs at Dartmouth College and Dartmouth- Hitchcock Medical Center. In addition, we will evaluate the ability of genomic surveillance of wastewater samples to serve as a sentinel for SARS-CoV-2 outbreaks in a congregate community where direct correlations can be made between wastewater samples and human specimens from the same geolocation. Understanding the distribution and infectivity of SARS-CoV-2 variants will enable public health agencies to provide more accurate and specific guidance on public health measures that need to be enacted to control COVID-19 based on the types of SARS-CoV-2 variants present in specific populations.