Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute, highly transmissible respiratory infection in humans and a wide range of animal species. Its rapid global spread has resulted in a major public health emergency, necessitating commensurately rapid research to improve control strategies. In particular, the ability to effectively retrace transmission chains in outbreaks remains a major challenge, partly due to our limited understanding of the virus’ underlying evolutionary dynamics within and between hosts. We used high-throughput sequencing whole-genome data coupled with bottleneck analysis to retrace the pathways of viral transmission in two nosocomial outbreaks that were previously characterised by epidemiological and phylogenetic methods. Additionally, we assessed the mutational landscape, selection pressures, and diversity at the within-host level for both outbreaks. Our findings show evidence of within-host selection and transmission of variants between samples. Both bottleneck and diversity analyses highlight within-host and consensus-level variants shared by putative source-recipient pairs in both outbreaks, suggesting that certain within-host variants in these outbreaks may have been transmitted upon infection rather than arising de novo independently within multiple hosts. Overall, our findings demonstrate the utility of combining within-host diversity and bottleneck estimations for elucidating transmission events in SARS-CoV-2 outbreaks, provide insight into the maintenance of viral genetic diversity, provide a list of candidate targets of positive selection for further investigation, and demonstrate that within-host variants can be transferred between patients. Together these results will help in developing strategies to understand the nature of transmission events and curtail the spread of SARS-CoV-2.

中文翻译：

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南非两次主要医院暴发中 SARS-CoV-2 宿主内多样性的传播动态


严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 可在人类和多种动物物种中引起急性、高度传染性呼吸道感染。其在全球的快速传播已导致重大公共卫生紧急事件，因此需要相应快速的研究来改进控制策略。特别是，在疫情爆发时有效追溯传播链的能力仍然是一个重大挑战，部分原因是我们对病毒在宿主内部和宿主之间的潜在进化动力学的了解有限。我们使用高通量测序全基因组数据结合瓶颈分析来追溯两次医院暴发中的病毒传播途径，这两次暴发之前是通过流行病学和系统发育方法进行表征的。此外，我们还评估了两次爆发的宿主内水平的突变情况、选择压力和多样性。我们的研究结果显示了宿主内选择和样本之间变异传播的证据。瓶颈和多样性分析都强调了两次爆发中推定来源-接受者对共享的宿主内和一致水平变异，表明这些爆发中的某些宿主内变异可能是在感染时传播的，而不是在多个宿主内独立从头产生的。总体而言，我们的研究结果证明了将宿主内多样性和瓶颈估计相结合对于阐明 SARS-CoV-2 爆发中的传播事件的效用，提供了对病毒遗传多样性维持的深入了解，并提供了用于进一步研究的正向选择的候选目标列表，并证明宿主内变异可以在患者之间转移。 这些结果将有助于制定策略来了解传播事件的性质并遏制 SARS-CoV-2 的传播。