新型冠状病毒（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）易发生变异。刺突（spike，S）蛋白是SARS-CoV-2与宿主细胞结合的重要结构，S蛋白的基因突变可能会改变病毒传染性、致病性、抗体应答等临床特征。世界卫生组织根据病毒的传染性、致病性和免疫逃逸能力，提出存疑变异株（variant of interest，VOI）和关切变异株（variant of concern，VOC）的分类。本文将对D614G变异株及流行的Alpha（B.1.1.7）、Beta（B.1.351）、Gamma（P.1）、Delta（B.1.617.2）和Epsilon（B.1.427/ B.1.429）变异株的最新研究进展进行概述。

目的:对引发2022年5月山东省荣成市COVID-19疫情的SARS-CoV-2进行全基因组测序，分析核苷酸和氨基酸变异情况并进行溯源。方法:应用高通量测序技术对15份来源于某水产进口公司相关COVID-19聚集性病例鼻咽拭子样本和3份环境样本进行病毒全基因组测序。使用病毒序列和变异分析软件，对测序原始数据进行全基因组序列拼接和变异位点分析并对病毒进行分型，利用进化分析软件构建系统发育树，并结合病例流行病学调查结果，追溯病毒的潜在来源。结果:成功获得13条来源于病例样本的SARS-CoV-2全基因组序列，长度为29 653~29 780 bp，平均测序深度为1 756~6 565 X，基因组覆盖度为99.20%~99.63%；Pangolin分型结果显示13个SARS-CoV-2基因组均属于VOC/Gamma(P.1.15)分支；与武汉参考株(NC_045512.2)相比，13条SARS-CoV-2全基因组序列分别存在40~41个核苷酸突变位点；在7个蛋白质结构域(ORF1a、ORF1b、S、ORF3a、ORF8、ORF9b及N蛋白)，存在23~24个氨基酸变异位点。进化分析显示该病毒序列与来自阿根廷的参考株(EPI_ISL_4082233)共处于同一子分支上。结论:本研究从荣成市一起冷链进口水产关联的COVID-19聚集性疫情病例样本中测序获得13个Gamma变异株全基因组序列，及时将病毒来源指向于2021年的南美进口海鲜。本研究所采用的测序方法和分析结果可以为SARS-CoV-2的变异分析和病例溯源提供参考，也提示我们SARS-CoV-2在冷链物品表面的存活与传播能力不容小觑，有待进一步探索。

目的:对山东省威海荣成市报告一起新型冠状病毒肺炎疫情进行溯源调查。方法:对新型冠状病毒（SARS-CoV-2）核酸检测阳性者及其密切接触者进行调查，对9株病毒毒株进行全基因组测序及遗传进化分析；从国内外两个源头，人、物和环境三个方面开展溯源调查。结果:本次疫情累计报告15例无症状感染者，包括某水产品加工公司车间13例，感染率为21.67%（13/60）；感染者的同村邻居2例（夫妻关系）。初次检出的6例感染者为从事清除鱿鱼内脏首道工序工人，首次咽拭子核酸检测Ct值为15~29，病毒载量高，疑为同源一次性暴露所致。9株病毒毒株全基因组序列高度同源，属于VOC/Gamma（P.1.15进化分支），与我国既往本土和输入病例均不同源；与智利上传的2021年5月5—26日采样的6条病毒序列高度同源。溯源结果显示，该公司近14日内使用过2021年5—6月在智利、阿根廷附近海域捕获的鱿鱼原材料；库存原材料、产品及其外包装多处采样核酸检测呈阳性。结论:本次疫情是我国首起由SARS-CoV-2 VOC/Gamma引起的本土聚集性疫情，可能为南美洲地区2021年5—6月期间流行的VOC/Gamma通过冷冻鱿鱼传入我国。

Dear Editor,The spread of the SARS-CoV-2 variants,especially the global variants of concern (VOCs),could seriously dampen our efforts to tackle the COVlD-19 pandemic.The SARS-CoV-2 spike protein recognizes the host angiotensin-converting enzyme 2 (ACE2) via its receptor-binding domain (RBD) to mediate viral entry into the cells.Several notorious mutations have been identified in the spike RBD of the VOCs.For example,B.1.1.7 (Alpha),B.1.351 (Beta),and P.1 (Gamma) all contain the N501Y mutation,which increases the binding affinity for human ACE2 and confers higher infectivity in mice.1,2 In addition,B.1.351 and P.1 carry the K417N/E484K and K417T/E484K substitutions,respectively,which drastically alter RBD surface electrostatics and lead to immune escapes.3,4 E484K has been detected in some strains of B.1.1.7 as well.Recently,the World Health Organization classified B.1.617.2 (Delta) as the fourth global VOC,which contains the L452R and T478K double mutations in the RBD.The L452R substitution has been shown to resist some neutralizing antibodies,s,6 and is present in other SARS-CoV-2 variants besides B.1.617.2,such as B.1.617.1 (Kappa)and B.1.427/B.1.429 (Epsilon).A L452Q mutation is found in C.37(Lambda).The functional significance of T478K remains to be understood.As this substitution also leads to an alteration in the electrostatic property of RBD,it may function as an escaping mutation to diminish the potency of some neutralizing antibodies as well.

Dear Editor,Since the declaration of public Health Emergency of Interna-tional Concern(PHEIC)by the WHO,the COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has led to over 300 million confirmed cases with more than 5 million deaths in the past 2 years.On top of that,SARS-CoV-2 continues evolving into many variants,and many of these variants with evidence to enhance viral transmissibility,adaptiveness,infectivity,and/or to escape from host immune response are classified as variants of concerns(VOC).1 Since the outbreak of the pandemic,five VOCs,including Alpha,Beta,Gamma,Delta,and Omicron have been verified by the WHO.

为了解输入中国大陆的新型冠状病毒(新冠病毒,SARS-CoV-2)基因组型别和分布特征,本研究收集了采样日期在2021年1月1日至2021年5月31日间239例境外输入中国大陆的SARS-CoV-2核酸检测阳性人员病毒基因组序列,采用Pangolin在线分型平台(https://pangolin.cog-uk.io/)进行SARS-CoV-2基因组分析.结果显示,2021年1月1日至2021年5月31日间,中国大陆23个省份报告了 SARS-CoV-2核酸检测阳性人员病毒序列,广东省报送的SARS-CoV-2基因组序列数最多(42.68％),其次为江苏省(12.13％).有序列报告的病例来自5个大洲的59个国家(或地区),主要以亚洲(55.23％)和非洲(25.10％)为主,居前3位的国家为肯尼亚、菲律宾和阿联酋,均为14例.依据Pango命名法,239例感染者SARS-CoV-2基因组序列可划分为53个基因型,包括4种关切变异株(Variant of Concern,VOC):Alpha(B.1.1.7)、Beta(B.1.351)、Gamma(P.1 和 P.1.1)和 Delta(B.1.617.2),占比分别为31.80％、14.23％、1.26％和9.62％,分别在14、8、2和6个省份监测发现.输入SARS-CoV-2的基因型以Alpha、Beta和Delta变异株为主.广东省监测发现的输入SARS-CoV-2基因型种类最多(36种),且包括4种VOC(Alpha、Beta、Gamma和Delta)和2种曾经定义的关注变异株(Epsilon和Eta).本研究数据表明,2021年1月1日至2021年5月31日期间输入中国大陆的SARS-CoV-2基因型呈多样性,多个省份监测发现了国际流行变异株VOC,发现时间与占比与同期国际流行趋势相似,多数省份面临着较大的由输入病例引起本土疫情的风险.建议继续加强入境核酸检测阳性人员SARS-CoV-2基因组测序、感染者的隔离管控以及对重要流行变异株的研究,从而为我国新型冠状病毒肺炎疫情的防控和免疫策略的调整提供科学依据.

The prevalence of SARS-CoV-2 variants of concern(VOCs)is still escalating throughout the world.However,the level of neutralization of the inactivated viral vaccine recipients'sera and convalescent sera against all VOCs,including B.1.1.7(Alpha),B.1.351(Beta),P.1(Gamma),B.1.617.2(Delta),and B.1.1.529(Omicron)remains to be lack of comparative analysis.Therefore,we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times.Our results show that,compared with the wild-type strain(WT),five VOC pseudoviruses showed higher infection,of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains,respectively.Sera from 10 vaccinated individuals at the 1,3 and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT.Notably,100％(30/30)of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529,and 90％(18/20)of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529.These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time,indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.