新型冠状病毒(SARS-CoV-2)的密码子偏爱性分析

目的 分析SARS-CoV-2密码子使用的偏爱性及不同国家和地区流行株的密码子之间的聚类关系。方法 使用CodonW、EMBOSS、SigmaPlot14.0、SPSS 22.0等软件分析SARS-CoV-2的密码子偏爱性及其影响因素,在此基础上对不同国家毒株的密码子偏爱性进行聚类分析。结果 SARS-CoV-2的各蛋白ENC值在26.60~57.81之间;密码子以A/U结尾(RSCU>1),约占84.98%。ACA、ACU、AGA、AUU、CCU、CUU、GCU、GGU、GUU、UCA、UCU、UUA为多数基因共有的高频密码子,ORF10基因没有偏爱密码子。ENC-Plot、中性分析、PR2绘图分析显示,SARS-CoV-2的各蛋白密码子使用偏爱性受不同因素影响,但是主要因素是自然选择,突变次之。基于密码子偏性的聚类分析发现,来源全球20多个国家和地区的SARS-CoV-2密码子偏爱性有明显差异。部分蛋白的密码子偏爱性聚类分析显示,西班牙、法国、韩国、美国和越南等国家单独聚类。S和ORF1ab的聚类分析显示,中国SARS-CoV-2流行株与美国的流行株的密码子使用偏性分属不同聚类。结论 SARS-CoV-2的密码子使用偏性在发生变化,目前主要受环境选择影响。这种改变可能是病毒的跨物种传播造成的,需对其加强动态监控,并对其密码子偏爱性改变的意义进行深入研究。     

尼帕病毒密码子偏爱性分析北大核心CSCD

目的了解尼帕病毒(Nipah Virus,NiV)主要蛋白密码子使用偏爱性及其影响因素,寻找最佳病毒蛋白表达系统。方法以人NiV的352条编码序列为材料,使用EMBOSS的子程序CAI和CUSP以及CodonW、SPSS22.0软件统计分析NiV 6个蛋白基因组密码子偏爱性,再用SigmaPlot14.0进行绘图。结果NiV各蛋白基因组ENC值分布在50.34~55.87之间,CAI值为0.678(0.606~0.730)。RSCU>1的密码子中以A/U结尾的约占43.3%。AGA、AGG、ACA、CUU、GUU、UCA为6个蛋白的多基因共有高频密码子。中性绘图分析、ENC-Plot分析和PR2奇偶分析表明自然选择是影响NiV密码子偏爱性的主要因素,同时突变因素也具有一定的作用。将NiV基因密码子使用频率与大肠埃希菌、酵母、人和昆虫杆状病毒表达系统进行比较,显示NiV与酵母密码子使用频率相差最小。结论NiV密码子在使用过程中偏爱A/U结尾,其偏爱性主要受自然选择作用的影响,酵母是最适于其蛋白表达的系统。     

老年新型冠状病毒Omicron感染者核酸转阴的相关因素分析

目的分析新型冠状病毒(SARS-CoV-2)Omicron变异株在老年非重症感染者的转阴时间,并探讨影响病毒核酸转阴的相关因素。方法104例老年新型冠状病毒肺炎(以下简称新冠)非重症病人根据病毒核酸转阴时间被分为早期转阴组(<10 d)和晚期转阴组(≥10 d)。收集并比较2组病人人口学资料、疫苗接种、基础疾病、血常规、生化指标、炎症指标、每次病毒核酸检测ORF1ab基因和N基因Ct值,并对转阴时间的影响因素行相关性分析。结果新型冠状病毒Omicron变异株在老年非重症感染者的平均转阴时间为(10.21±3.51)d,早期转阴组平均转阴时间为(7.26±1.54)d,晚期转阴组平均转阴时间为(12.96±2.44)d。2组年龄,合并慢性心力衰竭、慢性肺病的比例,新冠疫苗加强接种比例,首次病毒核酸Ct值差异均具有统计学意义(P<0.05)。Spearman相关分析结果显示,Omicron变异株转阴时间与年龄、慢性心力衰竭、血清降钙素原水平呈正相关,与新冠疫苗加强接种,首次病毒核酸基因Ct值呈负相关。多元线性回归分析显示,年龄、新冠疫苗加强接种、首次病毒核酸Ct值是核酸转阴时间的独立影响因素。结论老年新冠Omicron非重症感染者核酸转阴时间差异大,影响因素多;年龄、新冠疫苗加强针接种、首次病毒核酸Ct值是核酸转阴的独立影响因素。对老年群体行疫苗加强针接种可缩短核酸转阴时间。     

接种与未接种新型冠状病毒疫苗Omicron变异株感染患者临床表现、肝功能、抗体水平对比观察

目的 对比接种与未接种新型冠状病毒疫苗Omicron变异株感染患者的临床表现、肝功能、抗体水平。方法 选择天津市Omicron变异株感染的新型冠状病毒肺炎（COVID-19）恢复期患者430例,其中接种科兴疫苗150例（科兴组）,接种北京生物疫苗185例（北京生物组）,接种康希诺疫苗41例（康希诺组）,接种安徽智飞、长春生物、兰州生物、山东生物、其他腺病毒载体疫苗以及混合接种16例（其他组）,未接种疫苗38例（未接种组）。回顾性分析其临床资料,比较各组临床表现、肝功能相关指标[天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆红素（TB）、白蛋白（ALB）、总蛋白（TP）、乳酸脱氢酶（LDH）]以及抗体（IgG、IgM）水平。结果 各组性别构成比比较P均>0.05;北京生物组年龄明显低于其他组,北京生物组、康希诺组末次接种疫苗至入院时间<3个月的比例明显高于科兴组及其他组（P均<0.01）。年龄<16岁的患儿共110例,科兴组、北京生物组、康希诺组、其他组、未接种组分别为7、88、0、1、14例,无症状感染6例、普通型13例、轻型91例、重型0例。...     

云南新现蝙蝠SARS样冠状病毒密码子偏性及其聚类分析

目的 探索云南新现蝙蝠SARS样冠状病毒(SARSr-CoV)密码子偏性及其与SARS冠状病毒(SARS-CoV)及其他地区SARSr-CoV密码子偏性的进化关系。方法 运用Lasergene、EMBOSS、CodonW等生物信息软件,以SARS-CoV为对照,对云南新现蝙蝠SARSr-CoV各蛋白的编码序列进行密码子偏性分析,并基于此与不同时期报道的SARSr-CoV及SARS-CoV进行聚类分析。结果 11株云南新现蝙蝠SARSr-CoV各蛋白有效密码子数目均接近61,密码子偏性较弱;各蛋白偏性的密码子有差异,但均以A、U结尾的密码子为主。ENC-Plot、中性绘图分析与PR2规则分析均提示新现蝙蝠SARSr-CoV在进化过程中主要受到自然选择因素的影响。基于密码子偏性的聚类分析发现,部分云南蝙蝠SARSr-CoV与SARS-CoV关系极为密切。同时,其他云南SARSr-CoV分散聚类于其他地区的SARSr-CoV中。结论 新报道的蝙蝠SARSr-CoV的密码子偏性与SARS-CoV相似度较高,在进化过程中主要受到自然选择因素的影响,跨种传播至人的风险较高。     

新型冠状病毒Delta变异株感染患者早期实验室检查指标变化及疫苗保护作用观察

目的 观察新型冠状病毒(新冠病毒)Delta变异株感染患者外周血早期实验室检查指标及疫苗接种对新冠病毒Delta变异株感染患者的保护作用,为疫情防控提供参考.方法 2021年11月成都本土疫情中诊断为新冠病毒Delta变异株感染的年龄>18岁的新型冠状病毒肺炎(新冠肺炎)非重型患者25例,记为实验组,22例在感染前接种...     

新现HIV-1L亚型的密码子偏爱性研究北大核心CSCD

目的分析新现HIV-1L亚型密码子使用偏爱性及其影响因素,并基于密码子偏爱性分析L亚型与其他亚型之间的关系。方法依据HIV-1各亚型的基因编码序列,利用EMBOSS的子程序CUSP、CodonW和SPSS22.0软件对其密码子偏爱性进行统计分析,使用SigmaPlot进行绘图,并用MEGA10.0构建系统进化树,SPSS22.0进行聚类分析。结果HIV-1L亚型ENc为46.19,和其他型别(43.75~47.97)相当,其RSCU>1的密码子中A/U结尾的占约71.8%。中性绘图、ENc-plot及PR2-plot分析表明,包括L亚型在内的HIV-1密码子的偏爱性主要受自然选择的影响。系统发育分析显示新现L亚型与HIV-1M组C亚型的分离株形成一个分支。基于env和gag编码序列密码子偏爱性的聚类分析均显示L亚型与C亚型聚为一类。不论是系统发育分析还是聚类分析,其结果均表明L亚型与C亚型有着更密切的关系。结论新现L亚型HIV-1偏爱使用A/U结尾的密码子,其偏爱性主要受自然选择压力的影响。此外L亚型密码子偏爱性与流行较为广泛的HIV-1C亚型关系密切,需加强其流行病学监控。     

西安市重症新型冠状病毒Omicron变异株感染人群临床特征及预后风险因素分析

目的分析重症新型冠状病毒Omicron变异株感染人群免疫学、影像学临床特征及死亡预后风险因素。方法本研究为回顾性研究。采用非随机抽样法。选择2022年11月1日至2023年2月1日西安市第九医院确诊新型冠状病毒Omicron变异株感染重型及危重型患者为研究对象, 以2023年2月1日为时间点, 根据预后不同分为死亡组和生存组, 收集患者人口学资料、免疫学特征[自然杀伤细胞、T淋巴细胞、B淋巴细胞、免疫球蛋白(Ig)M、IgG、IgA]及胸部定量CT, 分析生存组与死亡组患者间数据的差异, 利用二元logistic回归分析影响重型及危重型Omicron变异株感染人群死亡的独立危险因素。利用受试者工作特征曲线比较不同生物学标志物之间的预测价值。结果共纳入重症新型冠状病毒Omicron变异株感染患者138例, 其中死亡组43例(男32例, 女11例), 生存组95例(男55例, 女40例), 2组性别构成比差异无统计学意义(χ2=3.47, P=0.063)。死亡组高龄患者、危重型患者占比高于生存组(χ2值分别为5.54、46.01, 均P<0.05)。死亡组淋巴细胞(CD4+T淋巴细...     

2019新型冠状病毒变异株的研究进展

2019新型冠状病毒(2019 novel coronavirus, 2019-nCoV)具有高度传染性。随着2019-nCoV在世界范围内的持续传播,病毒已出现多种变异株,其中,阿尔法(Alpha)、贝塔(Beta)、伽马(Gamma)、德尔塔(Delta)和拉姆达(Lambda)变异株表现出更高的传播性和致病性,严...     

Comparative Dynamics of Delta and Omicron SARS-CoV-2 Variants across and between California and Mexico

Evolutionary analysis using viral sequence data can elucidate the epidemiology of transmission. Using publicly available SARS-CoV-2 sequence and epidemiological data, we developed discrete phylogeographic models to interrogate the emergence and dispersal of the Delta and Omicron variants in 2021 between and across California and Mexico. External introductions of Delta and Omicron in the region peaked in early July (2021-07-10 [95% CI: 2021-04-20, 2021-11-01]) and mid-December (2021-12-15 [95% CI: 2021-11-14, 2022-01-09]), respectively, 3 months and 2 weeks after first detection. These repeated introductions coincided with domestic migration events with no evidence of a unique transmission hub. The spread of Omicron was most consistent with gravity centric patterns within Mexico. While cross-border events accounted for only 5.1% [95% CI: 4.3–6] of all Delta migration events, they accounted for 20.6% [95% CI: 12.4–29] of Omicron movements, paralleling the increase in international travel observed in late 2021. Our investigations of the Delta and Omicron epidemics in the California/Mexico region illustrate the complex interplay and the multiplicity of viral and structural factors that need to be considered to limit viral spread, even as vaccination is reducing disease burden. Understanding viral transmission patterns may help intra-governmental responses to viral epidemics.     

Impact of the Omicron variant on SARS-CoV-2 reinfections in France,March 2021 to February 2022

Since the first reports in summer 2020, SARS-CoV-2 reinfections have raised concerns about the immunogenicity of the virus, which will affect SARS-CoV-2 epidemiology and possibly the burden of COVID-19 on our societies in the future. This study provides data on the frequency and characteristics of possible reinfections, using the French national COVID-19 testing database. The Omicron variant had a large impact on the frequency of possible reinfections in France, which represented 3.8% of all confirmed COVID-19 cases since December 2021.     

Outbreak caused by the SARS-CoV-2 Omicron variant in Norway,November to December 2021

In late November 2021, an outbreak of Omicron SARS-CoV-2 following a Christmas party with 117 attendees was detected in Oslo, Norway. We observed an attack rate of 74% and most cases developed symptoms. As at 13 December, none have been hospitalised. Most participants were 30–50 years old. Ninety-six percent of them were fully vaccinated. These findings corroborate reports that the Omicron variant may be more transmissible, and that vaccination may be less effective in preventing infection compared with Delta.     

Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant contains extensive sequence changes relative to the earlier-arising B.1, B.1.1, and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (VLPs), we examined mutations in all four structural proteins and found that Omicron and Delta showed 4.6-fold higher luciferase delivery overall relative to the ancestral B.1 lineage, a property conferred mostly by enhancements in the S and N proteins, while mutations in M and E were mostly detrimental to assembly. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, or Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had 15-fold lower efficacy to prevent cell transduction by VLPs containing the Omicron mutations relative to the ancestral B.1 spike protein. A third dose of Pfizer vaccine elicited substantially higher neutralization titers against Omicron, resulting in detectable neutralizing antibodies in eight out of eight subjects compared to one out of eight preboosting. Furthermore, the monoclonal antibody therapeutics casirivimab and imdevimab had robust neutralization activity against B.1 and Delta VLPs but no detectable neutralization of Omicron VLPs, while newly authorized bebtelovimab maintained robust neutralization across variants. Our results suggest that Omicron has similar assembly efficiency and cell entry compared to Delta and that its rapid spread is due mostly to reduced neutralization in sera from previously vaccinated subjects. In addition, most currently available monoclonal antibodies will not be useful in treating Omicron-infected patients with the exception of bebtelovimab.

Understanding the molecular determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral fitness is central to effective vaccine and therapeutic development. The emergence of viral variants including Delta and Omicron underscores the need to assess both infectivity and antibody neutralization, but biosafety level 3 handling requirements slow the pace of research on intact SARS-CoV-2. Although vesicular stomatitis virus and lentivirus pseudotyped with the SARS-CoV-2 spike (S) protein enable evaluation of S-mediated cell binding and entry via the ACE2 and TMPRSS2 receptors, they cannot determine effects of mutations outside the S gene (1, 2). To address these challenges, we developed SARS-CoV-2 virus-like particles (SC2-VLPs) comprising the S, N, M, and E structural proteins and a packaging signal-containing messenger RNA (mRNA) that together form RNA-loaded capsids capable of spike-dependent cell transduction (3). This system faithfully reflects the impact of mutations in structural proteins that are observed in infections with virus isolates, enabling rapid testing of SARS-CoV-2 structural gene variants for their impact on both infection efficiency and antibody or antiserum neutralization.     

Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous SARS-CoV-2 infection with BNT162b2 vaccine, neutralizing titer against BA.1 and BA.2 were 20-fold decreased compared to titers against the parental D614G virus. A third immunization boosted overall neutralizing titers by about 5-fold but titers against BA.1 and BA.2 remained about 10-fold below that of D614G. Both Omicron variants were highly resistant to several of the emergency use authorized therapeutic monoclonal antibodies. The variants were highly resistant to Regeneron REGN10933 and REGN10987 and Lilly LY-CoV555 and LY-CoV016 while Vir-7831 and the mixture of AstraZeneca monoclonal antibodies AZD8895 and AZD1061 were significantly decreased in neutralizing titer. Strikingly, a single monoclonal antibody LY-CoV1404 potently neutralized both Omicron variants.     

珠海市新型冠状病毒奥密克戎变异株感染者心肌损害情况及心电图特征

目的]探索珠海市新型冠状病毒(SARS-CoV-2)奥密克戎变异株感染者心肌损害情况及异常心电图特征。 [方法]纳入2022年1月13日—3月20日中山大学附属第五医院收治的84例SARS-CoV-2奥密克戎变异株感染者(奥密克戎变异株组),以及2020年1月17日—2月17日收治的88例SARS-CoV-2非奥密克戎变异株感染者(非奥密克戎变异株组),采用回顾性研究比较两组患者的心肌损害情况、异常心电图情况及临床特征差异。 [结果]奥密克戎变异株组患者平均年龄小于非奥密克戎变异株组[(36.6±15.6)岁比(49.8±14.3)岁,P＜0.01],入院时体温、入院时收缩压及发热患者比例均低于非奥密克戎变异株组(P＜0.05)。奥密克戎变异株组患者中性粒细胞/淋巴细胞比值[(2.93(3.03,5.81)比7.06(2.2,1.27),P＜0.001]、白细胞介素2(IL-2)及白细胞介素6(IL-6)水平均明显低于非奥密克戎变异株组(P＜0.01)。奥密克戎变异株组心肌肌钙蛋白I(cTnI)均为阴性,cTnI、肌酸激酶同工酶(CK-MB)、N末端脑钠肽前体(NT-proBNP)浓度及其升高患者比例均明显低于非奥密克戎变异株组(P＜0.01)。奥密克戎变异株组患者异常心电图发生率亦明显低于非奥密克戎变异株组(25.0%比42.0%,P＝0.001),以窦性心动过速、房性早搏及T波改变为主,非奥密克戎变异株组患者以房性早搏、T波改变、ST段压低及束支传导阻滞为主。 [结论]珠海市SARS-CoV-2奥密克戎变异株感染者可能因绝大部分患者已接种新型冠状病毒疫苗而没有出现明显心肌损害,异常心电图发生率亦明显低于非奥密克戎变异株组,主要以窦性心动过速、房性早搏及T波改变为主。     

上海某方舱医院新型冠状病毒奥密克戎变异株感染者流行病学特征分析

[摘要]　目的　探讨上海某方舱医院新型冠状病毒奥密克戎变异株感染者的发病情况及流行病学特征。方法　以2022年4月9日—5月5日上海国家会展中心方舱医院收治的新型冠状病毒奥密克戎变异株感染者为研究对象,对感染者年龄、性别、地区、疫苗接种等疫情数据进行流行病学特征分析。结果　122 151例新型冠状病毒感染者均为奥密克戎变异株BA.2或BA.2.2亚型感染,其流行病学特征结果显示：患者男女比例为1.51:1;平均年龄为（44.91±15.38）岁;0～17岁、18～30岁、31～60岁和≥61岁感染者分别占4.74%、20.80%、62.52%和11.94%;无症状感染者占80.80%,轻型患者占19.20%;平均住院时间为（7.00±2.77）d;未接种和完成1、2和3次疫苗接种的感染者分别占20.30%、3.18%、31.30%和45.22%,其中≥61岁且完成3次疫苗接种的感染者仅占10.10%。结论　各个年龄段人群对于新型冠状病毒奥密克戎变异株普遍易感。无症状感染者是本次疫情的主体人群,临床症状不典型,早期隐匿传播,积极加强核酸检测是早期发现疫情的必要手段。     

Exercising the Sanger Sequencing Strategy for Variants Screening and Full-Length Genome of SARS-CoV-2 Virus during Alpha,Delta, and Omicron Outbreaks in Hiroshima

This study aimed to exercise the Sanger sequencing strategy for screening of variants among confirmed COVID-19 cases and validate our strategy against NGS strains in Hiroshima retrieved from GISAID. A total of 660 samples from confirmed COVID-19 cases underwent screening for variants by Sanger-based partial sequencing to the targeted spike gene (nt22,735~nt23,532) using an in-house-developed primer set. The identification of variants was done by unique checkpoints of base nucleotide changes in the targeted spike gene. Moreover, we amplified one full-length genome using Sanger method and an in-house-developed primer library. Using NGS strains of the same sampling period from GISAID, a phylogenetic tree was constructed to examine the distribution pattern of variants in Hiroshima and to validate our Sanger method. The modified primer set provided 100% validation and 99.2% amplification. PANGO Lineage R.1 was detected in late in the third wave, followed by Alpha (B.1.1.7) domination in the fourth wave, Delta (B.1.617.2) domination in the fifth wave, and Omicron (B.1.1.529) domination in the sixth wave, and there was no significant difference in viral copies between variants (p = 0.09). The variants showed different transmission patterns, but the distribution of variants is consistent to that shown by the phylogenetic tree. The Sanger method also provided successful amplification of the full-length genome of the SARS-CoV-2 virus. Our Sanger sequencing strategy was useful for the screening of SASR-CoV-2 variants without the need for full-genome amplification. The modified primer set was validated to use universally, which allows an understanding of the variants’ distribution in real time and provides the evidence for policy-making and the formulation or modification of preventive strategies.     

Genomic Diversity of SARS-CoV-2 Omicron Variant in South American Countries

Genomic surveillance of SARS-CoV-2 is one of the tools that provide genomic information on circulating variants. Given the recent emergence of the Omicron (B.1.1.529) variant, this tool has provided data about this lineage’s genomic and epidemiological characteristics. However, in South America, this variant’s arrival and genomic diversity are scarcely known. Therefore, this study determined the genomic diversity and phylogenetic relationships of 21,615 Omicron genomes available in public databases. We found that in South America, BA.1 (n = 15,449, 71%) and BA.1.1 (n = 6257, 29%) are the dominant sublineages, with several mutations that favor transmission and antibody evasion. In addition, these lineages showed cryptic transmission arriving on the continent in late September 2021. This event may have contributed to the dispersal of Omicron sublineages and the acquisition of new mutations. Considering the genomic and epidemiological characteristics of these lineages, especially those with a high number of mutations in their genome, it is important to conduct studies and surveillance on the dynamics of these lineages to identify the mechanisms of mutation acquisition and their impact on public health.