Pediatric Surgery Division, Department of Surgery/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr, Sardjito Hospital, Jl. Kesehatan No. 1, Yogyakarta, 55281, Indonesia.
Disease Investigation Center Wates, Directorate General of Livestock and Animal Health Services, Ministry of Agriculture, Yogyakarta, Indonesia.
BMC Med Genomics. 2021 Jun 1;14(1):144. doi: 10.1186/s12920-021-00990-3.
Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of SARS-CoV-2. We aimed to: (1) describe full genome characterization of SARS-CoV-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from Yogyakarta and Central Java, Indonesia and other countries.
The study involved 17 patients with COVID-19, including two family clusters. We determined the full-genome sequences of SARS-CoV-2 using the Illumina MiSeq next-generation sequencer. Phylogenetic analysis was performed using a dataset of 142 full-genomes of SARS-CoV-2 from different regions.
Ninety-four SNPs were detected throughout the open reading frame (ORF) of SARS-CoV-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations. About 94% (16/17) of the virus samples showed D614G on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including L5F, V83L, V213A, W258R, Q677H, and N811I. The virus samples from family cluster-1 (n = 3) belong to the same clade GH, in which two were collected from deceased patients, and the other from the survived patient. All samples from this family cluster revealed a combination of spike protein mutations of D614G and V213A. Virus samples from family cluster-2 (n = 3) also belonged to the clade GH and showed other spike protein mutations of L5F alongside the D614G mutation.
Our study is the first comprehensive report associating the full-genome sequences of SARS-CoV-2 with the epidemiological data within family clusters. Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection. This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes.
家庭内传播和多个刺突蛋白突变与 SARS-CoV-2 的快速传播有关。我们旨在：（1）描述 SARS-CoV-2 的全基因组特征，并将序列与家庭群内的流行病学数据相关联；（2）对来自印度尼西亚日惹和中爪哇以及其他国家的所有样本进行系统发育分析。
本研究纳入了 17 例 COVID-19 患者，包括两个家庭群。我们使用 Illumina MiSeq 下一代测序仪确定了 SARS-CoV-2 的全基因组序列。使用来自不同地区的 142 个 SARS-CoV-2 全基因组数据集进行系统发育分析。
在 SARS-CoV-2 样本的开放阅读框（ORF）中检测到 94 个单核苷酸多态性（SNP），其中 58%（54/94）的核酸变化导致氨基酸突变。约 94%（17/17）的病毒样本在刺突蛋白上显示 D614G，其中 56%（9/16）在该蛋白上显示其他各种氨基酸突变，包括 L5F、V83L、V213A、W258R、Q677H 和 N811I。来自家庭群 1（n=3）的病毒样本属于同一进化枝 GH，其中 2 个样本来自死亡患者，另一个来自存活患者。该家庭群的所有样本均显示 D614G 和 V213A 的刺突蛋白突变组合。来自家庭群 2（n=3）的病毒样本也属于进化枝 GH，并显示 L5F 与 D614G 突变一起的其他刺突蛋白突变。
我们的研究首次全面报告了 SARS-CoV-2 的全基因组序列与家庭群内的流行病学数据相关联。系统发育分析显示，来自家庭群 1 的三个病毒形成了一个单系群，而来自家庭群 2 的病毒形成了一个多系群，表明存在不同感染源的可能性。本研究强调了同一家庭成员之间相同的刺突蛋白突变如何导致不同的疾病结局。
