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江苏省感染 SARS-CoV-2 患者的临床特征和病毒株变异分析——一项回顾性研究。

Analysis of Clinical Characteristics and Virus Strains Variation of Patients Infected With SARS-CoV-2 in Jiangsu Province-A Retrospective Study.

机构信息

Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Front Public Health. 2021 Dec 24;9:791600. doi: 10.3389/fpubh.2021.791600. eCollection 2021.

Abstract

At present, the global sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) situation is still grim, and the risk of local outbreaks caused by imported viruses is high. Therefore, it is necessary to monitor the genomic variation and genetic evolution characteristics of SARS-CoV-2. The main purpose of this study was to detect the entry of different SARS-CoV-2 variants into Jiangsu Province, China. First, oropharyngeal swabs were collected from 165 patients (55 locally confirmed cases and 110 imported cases with confirmed and asymptomatic infection) diagnosed with SARS-CoV-2 infection in Jiangsu Province, China between January 2020 and June 2021. Then, whole genome sequencing was used to explore the phylogeny and find potential mutations in genes of the SARS-CoV-2. Last, association analysis among clinical characteristics and SARS-CoV-2 Variant of Concern, pedigree surveillance analysis of SARS-COV-2, and single nucleotide polymorphisms (SNPs) detection in SARS-COV-2 samples was performed. More men were infected with the SARS-CoV-2 when compared with women. The onset of the SARS-CoV-2 showed a trend of younger age. Moreover, the number of asymptomatic infected patients was large, similar to the number of common patients. Patients infected with Alpha (50%) and Beta (90%) variants were predominantly asymptomatic, while patients infected with Delta (17%) variant presented severe clinical features. A total of 935 SNPs were detected in 165 SARS-COV-2 samples. Among which, missense mutation (58%) was the dominant mutation type. About 56% of SNPs changes occurred in the open reading frame 1ab (ORF1ab) gene. Approximately, 20% of SNP changes occurred in spike glycoprotein (S) gene, such as p.Asp501Tyr, p.Pro681His, and p.Pro681Arg. In total, nine SNPs loci in S gene were significantly correlated with the severity of patients. It is worth mentioning that amino acid substitution of p.Asp614Gly was significantly positively correlated with the clinical severity of patients. The amino acid replacements of p.Ser316Thr and p.Lu484Lys were significantly negatively correlated with the course of disease. Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may further undergo a variety of mutations in different hosts, countries, and weather conditions. Detecting the entry of different virus variants of SARS-CoV-2 into Jiangsu Province, China may help to monitor the spread of infection and the diversity of eventual recombination or genomic mutations.

摘要

目前,全球严重急性呼吸系统综合症冠状病毒 2 型(SARS-CoV-2)形势仍然严峻,由输入性病毒引起的本地疫情暴发风险较高。因此,有必要监测 SARS-CoV-2 的基因组变异和遗传进化特征。本研究的主要目的是检测不同 SARS-CoV-2 变体进入中国江苏省的情况。首先,从 2020 年 1 月至 2021 年 6 月在中国江苏省诊断为 SARS-CoV-2 感染的 165 名患者(55 例本地确诊病例和 110 例输入性确诊和无症状感染病例)中采集咽拭子。然后,对全基因组进行测序,以探索 SARS-CoV-2 的系统发育,并发现基因中的潜在突变。最后,对 SARS-CoV-2 变异株与临床特征的关系、SARS-CoV-2 的谱系监测分析、SARS-CoV-2 样本中单核苷酸多态性(SNP)的检测进行了关联分析。与女性相比,更多的男性感染了 SARS-CoV-2。SARS-CoV-2 的发病呈年轻化趋势。此外,无症状感染患者数量较多,与普通患者数量相近。感染 Alpha(50%)和 Beta(90%)变异株的患者主要为无症状,而感染 Delta(17%)变异株的患者则表现出严重的临床特征。在 165 例 SARS-CoV-2 样本中检测到 935 个 SNP。其中,错义突变(58%)是主要的突变类型。大约 56%的 SNP 变化发生在开放阅读框 1ab(ORF1ab)基因中。约 20%的 SNP 变化发生在刺突糖蛋白(S)基因中,如 p.Asp501Tyr、p.Pro681His 和 p.Pro681Arg。S 基因中共有 9 个 SNP 位点与患者的严重程度显著相关。值得注意的是,S 基因中氨基酸取代 p.Asp614Gly 与患者的临床严重程度呈显著正相关。氨基酸取代 p.Ser316Thr 和 p.Lu484Lys 与病程呈显著负相关。严重急性呼吸系统综合症冠状病毒 2 型(SARS-CoV-2)可能会在不同的宿主、国家和天气条件下进一步发生多种突变。检测不同 SARS-CoV-2 病毒变体进入中国江苏省,有助于监测感染的传播和最终重组或基因组突变的多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c3a/8739897/7cb187eed114/fpubh-09-791600-g0001.jpg

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