Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities.
Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities.
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DOI：
10.3389/fcimb.2020.575613
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发表时间：
2020
影响因子：
5.7
通讯作者：
Yassine HM
中科院分区：
文献类型：
--
作者：
Al Khatib HA;Benslimane FM;Elbashir IE;Coyle PV;Al Maslamani MA;Al-Khal A;Al Thani AA;Yassine HM
背景：正在进行的SARS-COV-2大流行已经在全球感染了800多万人。大多数新冠肺炎患者要么无症状，要么症状轻微。然而，约15%的病例出现严重并发症，需要重症监护。决定疾病严重程度的因素尚未完全确定。目的：研究不同临床表现的COVID-19患者的宿主内病毒多样性。方法：比较19例轻症和27例重症SARS-COV-2的遗传多样性。从鼻咽样本中提取病毒RNA，并使用Illumina MiSeq平台进行测序。随后在共识和亚共识序列水平上对SARS-CoV-2基因组进行了深度测序分析。结果：所有病毒的一致序列非常相似，无论疾病严重程度如何，序列同源性均超过99.8%。然而，亚共识分析显示，轻度和重度病例在宿主内多样性方面存在显著差异。与轻度病例相比，症状严重的患者编码区和非编码区变异数量显著增加（p值0.001）。分析还显示，在严重病例中，某些变异的流行率更高。最重要的是，与轻度病例（平均= 6）相比，重症病例表现出明显更高的宿主内多样性（平均= 13）。此外，与年轻年龄组相比，60岁以上患者的宿主内多样性更高。结论：这些观察结果为宿主内多样性可能在COVID-19患者严重疾病结局的发展中发挥作用提供了证据；然而，需要进一步的研究来阐明这种联系。
Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly (p-value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.
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DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
DOI：
10.1016/j.jaci.2010.10.048
发表时间：
2011-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Huang YJ;Nelson CE;Brodie EL;Desantis TZ;Baek MS;Liu J;Woyke T;Allgaier M;Bristow J;Wiener-Kronish JP;Sutherland ER;King TS;Icitovic N;Martin RJ;Calhoun WJ;Castro M;Denlinger LC;Dimango E;Kraft M;Peters SP;Wasserman SI;Wechsler ME;Boushey HA;Lynch SV;National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
通讯作者：
National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
影响因子：
5.4
作者：
Cabot, B;Martell, M;Gómez, J
通讯作者：
Gómez, J
影响因子：
6.7
作者：
Lauring AS;Andino R
通讯作者：
Andino R
影响因子：
3.7
作者：
Guan WZ;Qiu GF;Feng-Liu
通讯作者：
Feng-Liu