Smet Mathias, Berkell Matilda, Górska Anna, Tacconelli Evelina, Kumar-Singh Samir, Malhotra-Kumar Surbhi
Laboratory of Medical Microbiology, University of Antwerp, Vaccine & Infectious Disease Institute, Antwerp, Belgium; Molecular Pathology Group, Cell Biology & Histology, University of Antwerp Faculty of Medicine and Health Sciences, Antwerp, Belgium.
Division of Infectious Diseases, University of Verona Department of Diagnostics and Public Health, Verona, Italy.
Virology. 2025 Sep;610:110584. doi: 10.1016/j.virol.2025.110584. Epub 2025 May 26.
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, significant research has focused on SARS-CoV-2 evolution and transmission. Most transmission studies rely on RT-qPCR and consensus sequencing for SARS-CoV-2 characterization, often overlooking the collection of viable genetically linked genomes characterized by one or more intra-host single nucleotide variants (iSNVs) within the same sample, defined as "quasispecies" (QS), which could influence disease outcomes. QS are highly variable in genomic position and frequency and have been proven to impact viral evolution substantially. Several de novo mutations were detected in QS before becoming lineage defining in variants of concern (VOCs). These mutations can also result from errors during replication and transcription leading to the development of defective viral genomes (DVGs) that are incapable of replicating, but important for propagating viral diversity during infection. In a continuously changing landscape of dominating VOCs and anti-SARS-CoV-2 therapy and vaccination strategies, this scoping review aims to summarize the current state-of-the-art and identify knowledge gaps in understanding QS development and their impact on intra-host SARS-CoV-2 evolution, virulence, and intra-host immunity. Finally, we explore the potential of studying inter-host transmission in households as a mirror for community transmission and evolution.
自2019年严重急性呼吸综合征冠状病毒2（SARS-CoV-2）出现以来，大量研究聚焦于SARS-CoV-2的进化和传播。大多数传播研究依靠逆转录定量聚合酶链反应（RT-qPCR）和一致性测序来表征SARS-CoV-2，常常忽略了在同一样本中收集以一个或多个宿主内单核苷酸变异（iSNV）为特征的、具有遗传联系的存活基因组，这些基因组被定义为“准种”（QS），而准种可能会影响疾病结局。准种在基因组位置和频率上高度可变，并且已被证明会对病毒进化产生重大影响。在成为关注变异株（VOC）的谱系定义变异之前，在准种中检测到了多个从头突变。这些突变也可能源于复制和转录过程中的错误，导致产生有缺陷的病毒基因组（DVG），这些基因组无法复制，但在感染期间对传播病毒多样性很重要。在不断变化的主要关注变异株以及抗SARS-CoV-2治疗和疫苗接种策略的背景下，本综述旨在总结当前的最新研究状况，并找出在理解准种形成及其对宿主内SARS-CoV-2进化、毒力和宿主内免疫的影响方面的知识空白。最后，我们探讨了将家庭中的宿主间传播研究作为社区传播和进化的一个缩影的潜力。
