RAPID: Deciphering Within-host Diversity and Multi-strain Infections in COVID-19

为了促进实时疫情管理和缓解策略，迫切需要了解COVID-19的传播情况。研究人员通过应用算法对COVID-19患者样本进行测序，重建了病毒的进化和传播历史。然而，一个关键的挑战是宿主中存在多种病毒株，这被当前的算法所忽视。该RAPID项目将通过开发算法来表征患者体内共存的病毒株的持续进化和传播，从而改善国家对COVID-19的应对。开发的算法将适用于未来的疾病爆发。这个RAPID项目旨在了解宿主内病毒多样性对当前COVID-19传播的影响。该项目将通过开发对COVID-19测序样本进行去卷积的算法来识别患者体内共存的病毒株。随后，该项目将评估这些共存菌株是否是多重感染事件的结果。最后，该项目将通过对其突变的蛋白质功能分析来量化已识别病毒株的严重性。结果将通过一个在线门户网站发布，使实验室和医院能够上传他们的测序读数，并生成COVID-19病毒株的注释和特征。总之，本研究的目标是通过调查病毒的进化起源及其在宿主物种中的遗传变异来了解SARS-CoV-2，以确定分子变异如何与宿主范围相关，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

To facilitate real-time outbreak management and mitigation strategies, there is an urgent need to understand the spread of COVID-19. Researchers reconstruct the evolutionary and transmission history of the virus by applying algorithms to sequencing samples of COVID-19 patients. However, a key challenge is the presence of multiple strains of the virus within hosts, which is overlooked by current algorithms. This RAPID project will improve the nation’s COVID-19 response by developing algorithms to characterize the ongoing evolution and spread of the viral strains that coexist within patients. The developed algorithms will be applicable to future disease outbreaks.This RAPID project seeks to understand the impact of within-host viral diversity on the current spread of COVID-19. The project will identify the viral strains coexisting in patients through the development of algorithms that deconvolve COVID-19 sequencing samples. Subsequently, the project will assess whether or not such coexisting strains are the result of multiple infection events. Finally, the project will quantify the severity of the identified viral strains through a protein functional analysis of their mutations. Results will be disseminated through an online portal that enable labs and hospitals to upload their sequencing reads and generate annotations and characterizations of COVID-19 viral strains.In summary, the goal of this research is to understand SARS-CoV-2 by investigating the evolutionary origins of the virus and its genetic variation within host species in order to determine how molecular variation correlates with host range, and to evaluate risk of further disease emergence.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.