在 57 个国家和印度,与 clade-G SARS-CoV-2 病毒以及年龄相关的因素与死亡率增加有关。

Association of clade-G SARS-CoV-2 viruses and age with increased mortality rates across 57 countries and India.

机构信息

National Institute of Biomedical Genomics, Kalyani, West Bengal, India.

National Institute of Biomedical Genomics, Kalyani, West Bengal, India.

出版信息

Infect Genet Evol. 2021 Jun;90:104734. doi: 10.1016/j.meegid.2021.104734. Epub 2021 Jan 27.

Abstract

Several reports have highlighted the contributions of host factors such as age, gender and co-morbidities such as diabetes, hypertension and coronary heart disease in determining COVID-19 disease severity. However, inspite of initial efforts at understanding the contributions of SARS-CoV-2 variants, most were unable to delineate causality. Hence, in this study we re-visited the contributions of different clades of viruses (G, GR and GH) along with other attributes in explaining the disparity in mortality rates among countries. A total of 26,642 high quality SARS-CoV-2 sequences were included and the A23,403G (S:D614G) variant was found to be in linkage disequilibrium with C14,408 U (RdRp: P323L). Linear regression analyses revealed increase in age [Odds ratio: 1.055 (p-value 0.000358)] and higher frequency of clade-G viruses [Odds ratio: 1.029(p-value 0.000135)] could explain 37.43% of the differences in mortality rates across the 58 countries (Multiple R-squared: 0.3743). Next, Machine-Learning algorithms LogitBoost and AdaboostM1 were applied to determine whether countries belonging to high/low mortality groups could be classified using the same attributes and accurate classification was achieved in 70.69% and 62.07% of the countries, respectively. Further, evolutionary analyses of the Indian viral population (n = 662) were carried out. Allele frequency spectrum, nucleotide diversity (π) values and negative Tajima's D values across ORFs were indicative of population expansion. Network analysis revealed the presence of two major clusters of viral haplotypes, namely, clade-G and a variant of clade L [L] having the RdRp:A97V amino acid change. Clade-G genomes were found to be evolving more rapidly and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal. Thus, the findings of this study and results from in vitro studies highlighting the role of these variants in increasing transmissibility and altering response to antivirals reflect the role of viral factors in disease prognosis.

摘要

已有多项报告强调了宿主因素(如年龄、性别和合并症,如糖尿病、高血压和冠心病)在确定 COVID-19 疾病严重程度方面的贡献。然而,尽管最初努力理解 SARS-CoV-2 变体的贡献,但大多数都无法确定因果关系。因此,在这项研究中,我们重新研究了不同病毒(G、GR 和 GH)分支以及其他属性在解释各国死亡率差异方面的贡献。共纳入了 26642 条高质量的 SARS-CoV-2 序列,发现 A23403G(S:D614G)变体与 C14408U(RdRp:P323L)呈连锁不平衡。线性回归分析显示,年龄增加[优势比:1.055(p 值 0.000358)]和 clade-G 病毒的高频率[优势比:1.029(p 值 0.000135)]可以解释 58 个国家死亡率差异的 37.43%(多重 R-平方:0.3743)。接下来,应用机器学习算法 LogitBoost 和 AdaboostM1 来确定是否可以使用相同的属性对属于高死亡率/低死亡率国家的国家进行分类,并且在 70.69%和 62.07%的国家中分别实现了准确的分类。此外,对印度病毒群体(n=662)进行了进化分析。ORFs 上的等位基因频率谱、核苷酸多样性(π)值和负 Tajima 的 D 值表明群体扩张。网络分析显示存在两个主要的病毒单倍型簇,即 clade-G 和具有 RdRp:A97V 氨基酸变化的 clade L [L]变体。clade-G 基因组的进化速度更快,在死亡率最高的三个州(古吉拉特邦、中央邦和西孟加拉邦)的比例也更高。因此,这项研究的结果和体外研究结果强调了这些变体在增加传染性和改变抗病毒药物反应方面的作用,反映了病毒因素在疾病预后中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2672/7839510/e2d5d279e72a/gr1_lrg.jpg

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