Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh.
Next Generation Sequencing, Research and Innovation Laboratory Chittagong (NRICh), Biotechnology Research and Innovation Center (BRIC), University of Chittagong, Chattogram, Bangladesh.
Immun Inflamm Dis. 2024 Feb;12(2):e1171. doi: 10.1002/iid3.1171.
The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on population health. The genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Bangladesh are not well understood.
This study aimed to determine the genomic variation in SARS-CoV-2 genomes that have evolved over 2 years of the pandemic in southern Bangladesh and their association with disease outcomes and virulence of this virus. We investigated demographic variables, disease outcomes of COVID-19 patients and genomic features of SARS-CoV-2.
We observed that the disease severity was significantly higher in adults (85.3%) than in children (14.7%), because the expression of angiotensin-converting enzyme-2 (ACE-2) diminishes with ageing that causes differences in innate and adaptive immunity. The clade GK (n = 66) was remarkable between June 2021 and January 2022. Because of the mutation burden, another clade, GRA started a newly separated clustering in December 2021. The burden was significantly higher in GRA (1.5-fold) highlighted in mild symptoms of COVID-19 patients than in other clades (GH, GK, and GR). Mutations were accumulated mainly in S (22.15 mutations per segment) and ORF1ab segments. Missense (67.5%) and synonymous (18.31%) mutations were highly noticed in adult patients with mild cases rather than severe cases, especially in ORF1ab segments. Moreover, we observed many unique mutations in S protein in mild cases compared to severe, and homology modeling revealed that those might cause more folding in the protein's alpha helix and beta sheets.
Our study identifies some risk factors such as age comorbidities (diabetes, hypertension, and renal disease) that are associated with severe COVID-19, providing valuable insight regarding prioritizing vaccination for high-risk individuals and allocating health care and resources. The findings of this work outlined the knowledge and mutational basis of SARS-CoV-2 for the next treatment steps. Further studies are needed to confirm the effects of structural and functional proteins of SARS-CoV-2 in detail for monitoring the emergence of new variants in future.
2019 年冠状病毒病(COVID-19)大流行对人口健康造成了严重影响。孟加拉国南部严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的遗传决定因素尚不清楚。
本研究旨在确定在孟加拉国南部 COVID-19 大流行的 2 年期间进化的 SARS-CoV-2 基因组中的基因组变异及其与该病毒的疾病结果和毒力的关系。我们调查了人口统计学变量、COVID-19 患者的疾病结果和 SARS-CoV-2 的基因组特征。
我们发现,成年人(85.3%)的疾病严重程度明显高于儿童(14.7%),因为血管紧张素转换酶-2(ACE-2)的表达随着年龄的增长而减少,这导致先天和适应性免疫的差异。2021 年 6 月至 2022 年 1 月期间,谱系 GK(n=66)非常显著。由于突变负担,另一个谱系 GRA 于 2021 年 12 月开始新的分离聚类。在 COVID-19 轻症患者中,GR 负担明显更高(是其他谱系 GH、GK 和 GR 的 1.5 倍)。突变主要积累在 S(每段 22.15 个突变)和 ORF1ab 段。在轻症成年患者中,错义(67.5%)和同义(18.31%)突变高度显著,而不是重症患者,特别是在 ORF1ab 段。此外,与重症患者相比,我们在轻症患者的 S 蛋白中观察到许多独特的突变,同源建模表明这些突变可能导致蛋白质的 alpha 螺旋和 beta 片层发生更多折叠。
我们的研究确定了一些与严重 COVID-19 相关的风险因素,如年龄合并症(糖尿病、高血压和肾脏疾病),为高危人群的疫苗接种提供了有价值的见解,并为医疗保健和资源的分配提供了依据。这项工作的结果概述了 SARS-CoV-2 的知识和突变基础,为下一步治疗提供了依据。需要进一步的研究来详细确认 SARS-CoV-2 结构和功能蛋白的作用,以便在未来监测新变体的出现。