Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.
Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.
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DOI：
10.1016/j.cell.2020.11.020
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发表时间：
2021-01-07
期刊：
影响因子：
64.5
通讯作者：
Connor TR
中科院分区：
文献类型：
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作者：
Volz E;Hill V;McCrone JT;Price A;Jorgensen D;O'Toole Á;Southgate J;Johnson R;Jackson B;Nascimento FF;Rey SM;Nicholls SM;Colquhoun RM;da Silva Filipe A;Shepherd J;Pascall DJ;Shah R;Jesudason N;Li K;Jarrett R;Pacchiarini N;Bull M;Geidelberg L;Siveroni I;COG-UK Consortium;Goodfellow I;Loman NJ;Pybus OG;Robertson DL;Thomson EC;Rambaut A;Connor TR
SARS-CoV-2刺突蛋白变异体D 614 G的全球扩散和频率增加表明了选择性优势，但也可能是由于随机创始人效应。我们使用超过25，000个全基因组SARS-CoV-2序列研究了英国Spike D 614 G阳性选择的假设。尽管有一个大的数据集的可用性，很好地代表了两个尖峰614变体，但并非所有的方法都显示出阳性选择的决定性信号。群体遗传分析表明，614 G相对于614 D以与选择优势一致的方式在频率上增加。我们没有发现任何迹象表明，感染尖峰614 G变异体的患者具有更高的COVID-19死亡率或临床严重程度，但614 G与更高的病毒载量和更年轻的患者年龄相关。614 G系统发育簇的生长和大小的显着差异表明需要继续研究这种变体。SARS-CoV-2 D 614 G频率的增加与选择性优势一致系统动力学分析未显示D 614 G簇的生长有显著差异D 614 G替换与更严重的感染无关D 614 G替换与更高的病毒载量和更年轻的患者年龄相关SARS-CoV传播和频率的分析2英国的D 614 G表明该毒株具有选择性优势，与年轻患者的病毒载量较高相关，但与COVID-19临床严重程度或死亡率较高无关。
Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant. Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage Phylodynamic analyses do not show significantly different growth of D614G clusters There is no association of D614G replacement with greater severity of infection The D614G replacement is associated with higher viral loads and younger patient age Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.