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

项目摘要/摘要 SARS-CoV-2大流行对全球公共卫生系统构成了挑战。令人担忧的几个变种 已经确定，其中一些增加了传播性、疾病严重性、再感染的风险和/或 对先前感染或接种疫苗的不同反应。在美国，尤其是在新罕布什尔州，这一数字 已经测序的SARS-CoV-2基因组的数量很少，但我们之前的研究大大增加了 努力。此外，SARS-CoV-2的测序工作主要针对有症状的 个人和/或特殊情况下的接触者追踪。我们目前在几个方面缺乏知识：(1) SARS-CoV-2变异株在区域社区出现的时间序列和地理位置；(2) 传染性增加与SARS-CoV-2变异之间的相关性；(3) 变异在不同种族、民族、性别和年龄组中的分布以及在 临床症状；以及(4)以前感染和/或接种疫苗的个人感染的程度 病毒以及哪些变种正在重新感染这些人。此外，SARS-CoV-2的废水监测 是一个有价值的公共卫生工具，但我们对SARS-CoV-2之间的关系缺乏了解 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组大型的、具有代表性的 SARS-CoV-2在NH状态下的变异并应用这一知识来更好地理解 这种特定的变种增加了病毒的传播性，逃避了以前那些 感染，或增加感染者出现临床症状的可能性。我们的中央 假设SARS-CoV-2变异株的全基因组序列分析将显示出显著的差异 在时间和地理位置流行方面，亚人群感染和发展的易感性 症状，以及感染其免疫系统以前受到挑战的个人的能力。 我们将对大约5000份存档和预期收集的SARS-CoV-2诊断样本进行测序 来自新汉普郡大学、NH卫生与人类事务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大学的新冠肺炎监测和临床测试项目- 希区柯克医疗中心。此外，我们还将评估废水的基因组监测能力。 样本作为SARS-CoV-2在聚集性社区中爆发的哨兵 可以在废水样本和来自同一地理位置的人类样本之间进行关联。 了解SARS-CoV-2变异株的分布和传染性将使公共卫生机构能够 就需要制定的公共卫生措施提供更准确和具体的指导 新冠肺炎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.