High Prevalence of SARS-CoV-2 Genetic Variation and D614G Mutation in Pediatric Patients With COVID-19.
High Prevalence of SARS-CoV-2 Genetic Variation and D614G Mutation in Pediatric Patients With COVID-19.
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儿童新冠肺炎患者SARS-CoV-2基因变异和D614G突变的高发研究
DOI：
10.1093/ofid/ofaa551
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发表时间：
2021-06
影响因子：
4.2
通讯作者：
Dien Bard J
中科院分区：
文献类型：
--
作者：
Pandey U;Yee R;Shen L;Judkins AR;Bootwalla M;Ryutov A;Maglinte DT;Ostrow D;Precit M;Biegel JA;Bender JM;Gai X;Dien Bard J
2019冠状病毒病（COVID-19）的疾病表型和病毒基因型的全谱尚未在儿童中进行彻底探索。在这里，我们分析了病毒遗传变异与儿童临床特征之间的关系。对2020年3月13日至6月16日期间收集的所有SARS-CoV-2阳性儿童（n = 141）的呼吸道标本进行全基因组测序。SARS-CoV-2基因组中的病毒遗传变异被鉴定和研究，以评估疾病严重程度的基因组相关性。在有症状的患者（P = .0007）和<5岁的儿童（P = .0004）中检测到较高的病毒载量。基因组分析显示平均成对差异为10.8个单核苷酸变异（SNV），大多数（55.4%）SNV导致病毒蛋白质中的氨基酸变化。99.3%的菌株存在纤突蛋白D 614 G突变。计算的病毒突变率为22.2个置换/年，与在无D 614 G突变的加州分离株中观察到的13.5个置换/年形成对比。进化枝20 C与COVID-19的严重病例相关（比值比，6.95; P = .0467）。流行病学调查显示，5个主要Nextstrain进化枝中的3个（20 A、20 B和20 C）具有主要代表性，这与SARS-CoV-2在南加州的多次引入一致。基因组评估表明，大于预期的遗传多样性，存在D 614 G突变，突变率增加，并有证据表明SARS-CoV-2多次引入南加州。我们的研究结果表明，系统发育进化枝20 C与严重疾病的可能关联，但小样本量排除了一个明确的结论。我们的研究需要进行更大规模的多机构基因组评估，并对感染控制实践产生影响。
The full spectrum of the disease phenotype and viral genotype of coronavirus disease 2019 (COVID-19) have yet to be thoroughly explored in children. Here, we analyze the relationships between viral genetic variants and clinical characteristics in children. Whole-genome sequencing was performed on respiratory specimens collected for all SARS-CoV-2-positive children (n = 141) between March 13 and June 16, 2020. Viral genetic variations across the SARS-CoV-2 genome were identified and investigated to evaluate genomic correlates of disease severity. Higher viral load was detected in symptomatic patients (P = .0007) and in children <5 years old (P = .0004). Genomic analysis revealed a mean pairwise difference of 10.8 single nucleotide variants (SNVs), and the majority (55.4%) of SNVs led to an amino acid change in the viral proteins. The D614G mutation in the spike protein was present in 99.3% of the isolates. The calculated viral mutational rate of 22.2 substitutions/year contrasts the 13.5 substitutions/year observed in California isolates without the D614G mutation. Phylogenetic clade 20C was associated with severe cases of COVID-19 (odds ratio, 6.95; P = .0467). Epidemiological investigation revealed major representation of 3 of 5 major Nextstrain clades (20A, 20B, and 20C) consistent with multiple introductions of SARS-CoV-2 in Southern California. Genomic evaluation demonstrated greater than expected genetic diversity, presence of the D614G mutation, increased mutation rate, and evidence of multiple introductions of SARS-CoV-2 into Southern California. Our findings suggest a possible association of phylogenetic clade 20C with severe disease, but small sample size precludes a definitive conclusion. Our study warrants larger and multi-institutional genomic evaluation and has implications for infection control practices.
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影响因子：
64.8
作者：
Plante JA;Liu Y;Liu J;Xia H;Johnson BA;Lokugamage KG;Zhang X;Muruato AE;Zou J;Fontes-Garfias CR;Mirchandani D;Scharton D;Bilello JP;Ku Z;An Z;Kalveram B;Freiberg AN;Menachery VD;Xie X;Plante KS;Weaver SC;Shi PY
通讯作者：
Shi PY
影响因子：
5.3
作者：
Sagulenko P;Puller V;Neher RA
通讯作者：
Neher RA
影响因子：
4.6
作者：
Isabel, Sandra;Grana-Miraglia, Lucia;Poutanen, Susan M.
通讯作者：
Poutanen, Susan M.
影响因子：
56.9
作者：
Deng, Xianding;Gu, Wei;Chiu, Charles Y.
通讯作者：
Chiu, Charles Y.
DOI：
10.1126/science.1259657
发表时间：
2014-09-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gire SK;Goba A;Andersen KG;Sealfon RS;Park DJ;Kanneh L;Jalloh S;Momoh M;Fullah M;Dudas G;Wohl S;Moses LM;Yozwiak NL;Winnicki S;Matranga CB;Malboeuf CM;Qu J;Gladden AD;Schaffner SF;Yang X;Jiang PP;Nekoui M;Colubri A;Coomber MR;Fonnie M;Moigboi A;Gbakie M;Kamara FK;Tucker V;Konuwa E;Saffa S;Sellu J;Jalloh AA;Kovoma A;Koninga J;Mustapha I;Kargbo K;Foday M;Yillah M;Kanneh F;Robert W;Massally JL;Chapman SB;Bochicchio J;Murphy C;Nusbaum C;Young S;Birren BW;Grant DS;Scheiffelin JS;Lander ES;Happi C;Gevao SM;Gnirke A;Rambaut A;Garry RF;Khan SH;Sabeti PC
通讯作者：
Sabeti PC