PDF(Pubmed)
Abstract：
During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral therapies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants which strongly challenged containment measures and some therapeutic treatments. To assess whether impaired immunity could lead to the increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimise the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients experienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low-frequency mutations. This study suggests that a compromised immune system alone does not affect SARS-CoV-2 within-host genomic variability.
摘要：
在COVID-19大流行期间，免疫抑制患者表现出长期的SARS-CoV-2感染，几项研究报告了病毒基因组中突变的积累。这些个体的免疫系统减弱，随着抗病毒治疗的效果，被认为为宿主内病毒进化创造了有利的环境，并且与新的病毒变体的出现有关，这些变体强烈挑战了遏制措施和一些治疗性治疗。为了评估免疫力受损是否会导致病毒基因组的不稳定性增加，纵向鼻咽拭子从8名免疫受损患者和14名非免疫受损受试者中收集，都经历了SARS-CoV-2感染.通过深度测序比较两组之间的宿主内病毒进化，利用基于探针的富集方法来最大程度地减少基于扩增子的方法中通常产生的人为突变的可能性，严重依赖PCR扩增。虽然,正如预期的那样，免疫功能低下的患者经历了明显更长的感染，两组之间新的宿主内病毒突变的获得相似.此外，对病毒准种的全面分析表明，两组病毒种群的变异性不仅在共识水平上具有可比性，而且在考虑低频突变时也是如此。这项研究表明，单独的免疫系统受损不会影响SARS-CoV-2宿主基因组内的变异性。
