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Virological Characteristics of the Omicron Variant: Key Mutations, Pathogenicity, and Immune Escape
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摘要: 新型冠状病毒(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) Omicron变异株首次在博茨瓦纳被检出, 随后造成了全世界范围内的感染人数激增。截至目前, Omicron是需要关注的SARS-CoV-2变异株中突变数量最多的毒株, 已在整个基因组中发生至少50次突变。Omicron基因组发生的突变赋予病毒一定的适应性优势, 如受体结合域与人类血管紧张素转换酶2受体亲和力增强导致病毒传播能力增强; 与先前变异株相比, 病毒复制能力减弱导致在COVID-19患者中引起的症状相对较轻。此外, 该变异株具有较高的环境稳定性, 部分逃脱了来自疫苗接种或先前感染诱导的宿主免疫反应, 且对大多数治疗性抗体具有较高的耐药性。本文对Omicron变异株的关键突变、病毒学特征、致病性和免疫逃逸能力进行总结, 以期为完善疫情防控策略和公共卫生举措提供科学参考。Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was first detected in Botswana and subsequently led to a worldwide surge in infections. Until now, Omicron and its lineages, the most highly mutated strains among variants of concern (VOC), have contained at least 50 mutations in the entire genome. Mutations give the virus certain adaptive advantages, such as the enhanced affinity between receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptors leading to enhanced transmission of the virus, and the weakened ability of virus replication leading to mild symptoms in patients with COVID-19. In addition, given its high environmental stability, Omicron can partially escape the host immune response induced by vaccination or prior infection, and is highly resistant tomost therapeutic antibodies.In this paper, key mutations, virological characteristics, pathogenicity, and immune escape of the Omicron variant are summarized, in order to provide scientific reference for coping with the new situation of the pandemic, as well as improving pandemic prevention and control strategy and public health measures.
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Keywords:
- Omicron variant /
- mutations /
- virological characteristics /
- pathogenicity /
- immune escape /
- COVID-19
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临床实习是医学本科生从理论向临床的过渡阶段，也是从医学生向独立医生转变的重要过程，其中临床技能培训是不可或缺的一环。目前，我国临床技能培训模型包括橡胶模具、假人、模拟器和活体动物等[1]，但橡胶模具和假人真实度差、精细度低，模拟器和活体动物则花费较高。此外，目前的技能培训通常将外科操作分开练习，难以实现将独立的技能运用到连贯的手术中。同时，随着外科手术技术的进步、微创外科的发展和手术流程的优化，对于实习医生来说，能在真实手术中进行操作练习的机会大大减少[2-3]。因此，本团队在美国芝加哥大学医学中心(The University of Chicago Medical Center, UCM)和加州大学旧金山分校医疗中心(University of California, San Francisco Health, UCSF Health)的协助下，通过互联网远程指导，改良设计了符合中国临床医学本科生培养实际情况的7种外科模拟手术模块，并将其命名为“全要素外科模拟手术教学”。本研究为回顾性分析，将该教学模式与传统规范化培训进行比较，观察接受两种不同培训模式的学生临床操作水平及接受度。
1. 资料与方法
1.1 研究对象与分组
以2019年10月至2020年10月，在北京协和医院实习的北京协和医学院临床医学专业学生为研究对象。通过抽签法随机将学生分为试验组(全要素外科模拟手术教学组)和对照组(传统规范化培训教学组)。
1.2 教学方法
课题组每周二开展外科临床技能开放培训班，对照组及试验组根据相应教材各教授1项内容，学生可根据个人时间安排自行选择参加相应组别的培训。课前均提前3 d向两组发放本团队录制的教学录像、PPT课件等供学生预习。
试验组依据课题组编写的《全要素外科模拟手术教学》教程，设置常见的手术模拟情景教学，向学生讲解、演示手术及围术期操作过程。培训内容共包括7个模块，详见表 1。教学过程中将对照组教学内容充分融合其中，如小肠切除吻合术中同时包含消毒铺巾、切开缝合等操作；腹壁疝修补术中同时包含消毒铺巾、切开缝合、换药拆线等操作；肺叶切除术中同时包含消毒铺巾、切开缝合、胸腔闭式引流拔除等操作；小腿截肢术中同时包含清创、脓肿切开等操作。
表 1 试验组全要素外科模拟手术教学培训模块对照组则严格按照国家医学生考试大纲设置培训内容，以《外科实习医师手册》《外科学》《教育部临床能力认证系列丛书一中国医学生临床技能操作指南》作为教材进行培训，培训内容包括：消毒铺巾、切开缝合、结扎止血、换药拆线、清创、脓肿切开、胸腔闭式引流拔除7项内容。
培训过程中两组各由1名主治医师通过操作示范向学生讲授培训内容的操作要点、方法及注意事项，学生分组模仿训练，教师巡视观察，现场纠正、演示。每次课程90 min，课后两组学生均可将操作模具带回自行练习1周，如有疑问，可及时反馈。研究结束后根据学生意愿，可选择参加与先前不同组的培训。
1.3 教学效果评估
(1) 学生完成所有课程后进行技能考核，考核内容包括消毒铺巾、切开缝合、结扎止血、换药拆线、清创、脓肿切开、胸腔闭式引流拔除7项内容。两组学生乱序进行测试，由未参与本次教学的外科临床医师进行作评分，严格按照当年国家临床执业医师资格考试实践技能评分标准，每项操作均以百分制计，评分内容包括操作前准备、操作步骤及人文关怀等。
(2) 参与课程后，学生通过线上/纸质问卷填写团队设计的外科临床技能培训反馈调查表，内容包含对自我操作能力、自我临床思维能力、自我学习效率及教学方式接受度的评价4个部分，每部分满分均为25分，总分以百分制计。
1.4 统计学处理
采用SPSS 25.0软件进行统计学分析。计量资料以均数±标准差表示，组间比较采用t检验，以P＜0.05为差异有统计学意义。
2. 结果
2.1 一般资料
共80名学生接受了培训，其中对照组和试验组各40名。两组性别、年龄差异无统计学意义(P均＞0.05)。
2.2 两组外科临床技能操作考核成绩比较
试验组在外科临床技能操作考核中，消毒铺巾、切开缝合、结扎止血、换药拆线、清创、脓肿切开、胸腔闭式引流拔除成绩均高于对照组(P均＜0.01)。见表 2。
表 2 两组外科临床技能操作考核成绩比较(x±s，分)组别 消毒铺巾 切开缝合 结扎止血 换药拆线 清创 脓肿切开 胸腔闭式引流拔除 试验组(n=40) 90.88±4.42 86.33±5.45 89.00±4.70 91.15±5.29 89.00±4.31 87.70±5.17 90.58±5.56 对照组(n=40) 75.93±4.87 72.80±8.16 72.38±7.26 73.05±5.78 70.40±5.35 70.38±7.99 75.25±7.65 t值 14.376 8.720 12.157 14.614 17.190 11.511 9.994 P值 ＜0.01 ＜0.01 ＜0.01 ＜0.01 ＜0.01 ＜0.01 ＜0.01 2.3 两组问卷调查结果比较
共发放调查问卷80份，收回有效问卷80份，有效问卷回收率为100%。试验组对自我操作能力、自我临床思维能力、自我学习效率、教学方式接受度的评分均显著高于对照组(P均＜0.05, 表 3)。
表 3 两组问卷调查结果比较(x±s，分)组别/评价 自我操作能力 自我临床思维能力 自我学习效率 教学方式接受度 总分 试验组(n=40) 21.95±2.68 21.13±2.76 21.83±2.99 22.13±2.50 87.03±4.23 对照组(n=40) 19.15±4.53 18.33±3.24 19.83±4.14 19.18±2.75 76.48±4.41 t值 3.37 4.17 2.48 5.01 10.91 P值 ＜0.01 ＜0.01 0.02 ＜0.01 ＜0.01 3. 讨论
全要素外科模拟手术教学是本团队受UCSF所提倡的教学理念启发后，结合我国医学生培训情况，创新设计的教学方法。该方法不用活体动物和高大上的模拟仪器设备，而是采用易获得且价廉物美的动物器官(比如猪的肝脏、肺脏、大肠，甚至五花肉等)，结合临床案例，逼真模拟各种小手术(比如肝切除术、肺切除术、疝修补术等)，并进行分解教学和模拟操作，其中包括基本操作技能(打结、缝合等)和外科实践技能(分离结扎、血管重建等)的训练。模型中将动作逐一分解，规定每一步动作名称，统一教学，形成标准化和规范化的教学流程。因该教学内容中包含完整的基本操作方法和全面的手术操作要素，故取名为“全要素外科模拟手术教学”。
本研究试验组考核成绩显著高于对照组(P＜0.01)，提示全要素外科模拟手术教学相较于传统规范化培训，能够显著提高本科生操作水平。原因包括：(1)试验组包括所有外科基本操作，每个模块不仅关注操作本身，且更加注重完整的手术教学过程，例如“肺叶切除术”中，学生可学习到术前准备(手术指征、手术范围定位、消毒铺巾)、手术过程(切开缝合、分离切除、结扎止血等)、术后管理(术后并发症、换药拆线、拔除引流等)，而非单纯手术切除过程，虽未针对测试内容进行培训，但该组学生在操作过程中已掌握基本外科技能。技能操作只是外科体系中的一个重要环节，与之相关的术前准备、术后管理以及在此基础上形成的外科理念也是影响手术成败的关键因素[5]。(2)虽然两组授课总时长一致，但对照组是将各项技能分开培训，每项技能只在一次课程中重复练习，而试验组每个培训模块均包含消毒铺巾、切开缝合、结扎止血、换药拆线等多项技能，使学生得以反复练习，技能操作更加熟练。(3) 试验组中各项操作环环相扣，例如铺巾范围不对会影响后续操作的视野、缝合技术不过关会导致小肠无法吻合或切口无法闭合等，使学生更容易发现操作中的问题，针对自身不足之处进行练习，使操作水平进一步提升。(4)对照组为单人练习操作，而试验组需学生相互配合完成，这有助于提高团队协作能力及提高学习效率。
试验组在自我操作能力、自我临床思维能力、自我学习效率以及教学方式接受度方面的评分均显著高于对照组(P均＜0.05)，说明学生对全要素外科手术教学模式更为满意，这可能得益于仿照人体结构与功能的真实模拟道具和将情景操作融为一体的临床案例，且教学配有手术器械，使学生不仅练习了基本操作，更培养了良好的临床思维[6]。
综上，全要素外科模拟手术教学作为一种新型教学模式，能够提高实习医生的临床技能操作能力，教学效果良好且深受欢迎。但仍存在不足之处：(1)操作细节方面有待完善。(2)培训教师需要加强对培训内容的理解，将丰富的临床经验应用到教学中，摆脱既往死板的教学理念。(3)增强现实技术可将虚拟信息添加到真实世界，让体验者更好地将虚拟与现实进行交互[7]，如能将这一技术应用到教学之中，可更真实地模拟人体构造与生理，为实习医生提供更有效、更规范、更精确的外科技能培训方法。
作者贡献：陈玉清负责资料收集和论文撰写；李金明负责选题设计并审阅定稿。利益冲突：所有作者均声明不存在利益冲突 -
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