始终遵循当地感染防控规程;这里仅详细介绍基本原则。
立即将所有疑似或确诊病例隔离在与其他患者分开的区域。如果可能,将患者置于通风良好的单人房间内。若无法安置于单人房间,将所有病例置于同一房间内,并确保患者之间至少保持 1 m(3 ft)距离。[330]World Health Organization. Infection prevention and control during health care when coronavirus disease (COVID-19) is suspected or confirmed: interim guidance. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC-2020.4
始终执行标准防护措施:[330]World Health Organization. Infection prevention and control during health care when coronavirus disease (COVID-19) is suspected or confirmed: interim guidance. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC-2020.4
执行手和呼吸道卫生措施
给予患者佩戴医用口罩
穿戴适当的个人防护装备
实施安全的废弃物管理和环境清洁举措。
进入病例收容房间前,应对于飞沫和接触施行额外防护措施:[330]World Health Organization. Infection prevention and control during health care when coronavirus disease (COVID-19) is suspected or confirmed: interim guidance. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC-2020.4
在进行产生气溶胶操作时,采取空气传播防护措施,包括将患者置于负压房间内。[330]World Health Organization. Infection prevention and control during health care when coronavirus disease (COVID-19) is suspected or confirmed: interim guidance. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC-2020.4
所有为实验室检测而收集的标本都应视为具有潜在传染性。[330]World Health Organization. Infection prevention and control during health care when coronavirus disease (COVID-19) is suspected or confirmed: interim guidance. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC-2020.4
适当的个人防护装备可为医务工作者提供针对 COVID-19 的高水平防护。一项对 420 名派遣至武汉,使用适当个人防护装备的医务工作者所进行横断面研究表明,尽管所有研究纳入者都与 COVID-19 患者曾产生直接接触,并至少进行过一项气溶胶生成性操作,但其返家时严重急性呼吸综合征冠状病毒 2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)分子和血清学检测均为阴性。[331]Liu M, Cheng SZ, Xu KW, et al. Use of personal protective equipment against coronavirus disease 2019 by healthcare professionals in Wuhan, China: cross sectional study. BMJ. 2020 Jun 10;369:m2195.
https://www.bmj.com/content/369/bmj.m2195
http://www.ncbi.nlm.nih.gov/pubmed/32522737?tool=bestpractice.com
诸如流感等病毒性呼吸道疾病暴发时,标准外科口罩与呼吸器面罩对于防止医务工作者感染同样有效,但尚不清楚这一结论是否适用于 COVID-19。[332]Centre for Evidence-Based Medicine; Greenhalgh T, Chan XH, Khunti K, et al. What is the efficacy of standard face masks compared to respirator masks in preventing COVID-type respiratory illnesses in primary care staff? 2020 [internet publication].
https://www.cebm.net/what-is-the-efficacy-of-standard-face-masks-compared-to-respirator-masks-in-preventing-covid-type-respiratory-illnesses-in-primary-care-staff/
已有详细的感染防控指南:
社区环境中使用口罩的建议因国家而异。[337]Feng S, Shen C, Xia N, et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118603/
http://www.ncbi.nlm.nih.gov/pubmed/32203710?tool=bestpractice.com
在某些国家或特定情况,公共场所必须佩戴口罩,而在某些国家,则可根据当地文化习惯佩戴口罩。请参阅当地指南以获取更多信息。
无高质量或直接科学证据支持健康人士在社区环境中广泛使用口罩,因此须对风险和获益加以考虑。[95]World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance. 2020 [internet publication].
https://www.who.int/publications-detail/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak
[338]Mahase E. Covid-19: what is the evidence for cloth masks? BMJ. 2020 Apr 7;369:m1422.
https://www.bmj.com/content/369/bmj.m1422.long
http://www.ncbi.nlm.nih.gov/pubmed/32265341?tool=bestpractice.com
口罩对于呼吸道感染预防有效性的证据强度在医疗机构中高于社区环境;SARS-CoV-2 感染比较有效性的直接证据暂缺。[339]Chou R, Dana T, Jungbauer R, et al. Masks for prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings: a living rapid review. Ann Intern Med. 2020 Jul 20 [Epub ahead of print].
https://www.acpjournals.org/doi/10.7326/M20-3213
http://www.ncbi.nlm.nih.gov/pubmed/32579379?tool=bestpractice.com
世界卫生组织(World Health Organization, WHO)建议 COVID-19 有症状者应佩戴医用口罩、自我隔离并尽快寻求医学建议。WHO 当前亦鼓励民众在特定情况和环境中佩戴医用口罩或布料口罩(例如在已知或疑似广泛传播的区域,以及实施其他抑制措施[如社交疏离、接触者追踪和检测]能力有限或无能力地区;社交疏离无法达成的环境,尤其是易感人群)。该建议仅基于观察性证据。[95]World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance. 2020 [internet publication].
https://www.who.int/publications-detail/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak
WHO 不建议社区环境中 5 岁以下儿童佩戴口罩预防 COVID-19。[340]World Health Organization. Advice on the use of masks for children in the community in the context of COVID-19. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC_Masks-Children-2020.1
美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)建议,在难以维持社交疏离措施的公共场所(例如药店、超市),尤其是社区传播严重地区,可佩戴自制的布料口罩。[341]Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings, especially in areas of significant community-based transmission. 2020 [internet publication].
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover.html
仅使用口罩,不足以提供足够防护,应与其他感染防控措施结合采用,例如频繁进行手部清洁和保持社交疏离。重要的是,佩戴口罩之前,先用肥皂和水(或酒精为基础成分的消毒剂)洗手,并且需正确摘除口罩。使用过的口罩应妥善丢弃。[95]World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance. 2020 [internet publication].
https://www.who.int/publications-detail/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak
佩戴口罩的潜在危害和弊端包括:由于佩戴口罩和触摸面部/眼,或不更换潮湿或污损的非医用口罩,自发污染风险增加;头痛和/或呼吸困难;面部皮肤病变、刺激性皮炎或痤疮恶化;不适;沟通困难;社会和心理接受度;错误的安全感;依从性不佳;废弃物管理问题;对于患有慢性呼吸道疾病或存在呼吸问题的患者而言,困难重重。[95]World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance. 2020 [internet publication].
https://www.who.int/publications-detail/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak
口罩也可能形成潮湿环境,从而使病毒保持活性,增加呼吸道病毒载量;因佩戴口罩而出现的深大呼吸可能将病毒送入更深的肺部组织。[342]Lazzarino AI, Steptoe A, Hamer M, et al. Covid-19: important potential side effects of wearing face masks that we should bear in mind. BMJ. 2020 May 21;369:m2003.
https://www.bmj.com/content/369/bmj.m2003
http://www.ncbi.nlm.nih.gov/pubmed/32439689?tool=bestpractice.com
与医用级口罩相比,布料口罩在防止病毒传播方面的效力有限。[343]Sharma SK, Mishra M, Mudgal SK. Efficacy of cloth face mask in prevention of novel coronavirus infection transmission: a systematic review and meta-analysis. J Educ Health Promot. 2020 Jul 28;9:192.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497125/
http://www.ncbi.nlm.nih.gov/pubmed/33015206?tool=bestpractice.com
口罩效力取决于所用材料的类型、层数、吸湿性以及口罩与面部贴合度。一项比较布料口罩和外科口罩在医务工作者中的使用研究显示,布料口罩组所有感染结局发生率最高,该组流感样疾病发病率更高,且具有统计学意义。潮湿、重复使用布料口罩和过滤不良,可导致感染风险增加。[344]MacIntyre CR, Seale H, Dung TC, et al. A cluster randomised trial of cloth masks compared with medical masks in healthcare workers. BMJ Open. 2015 Apr 22;5(4):e006577.
https://bmjopen.bmj.com/content/5/4/e006577
http://www.ncbi.nlm.nih.gov/pubmed/25903751?tool=bestpractice.com
许多国家已实施强制性社交疏离举措,以减少和延缓传播(例如封锁城市、下达居家令、执行宵禁、关闭非必要商业场所、禁止集会、关闭学校和大学、旅行限制和禁令、远程工作、对暴露人群进行隔离检疫等)。
尽管 COVID-19 社交疏离证据有限,但仍在不断涌现,并且现有最佳证据似乎支持社交疏离措施,以减少播散和延缓传播。此类措施的时机和持续时间,似乎较为关键。[352]Centre for Evidence-Based Medicine; Mahtani KR, Heneghan C, Aronson JK. What is the evidence for social distancing during global pandemics? 2020 [internet publication].
https://www.cebm.net/covid-19/what-is-the-evidence-for-social-distancing-during-global-pandemics/
[353]Lewnard JA, Lo NC. Scientific and ethical basis for social-distancing interventions against COVID-19. Lancet Infect Dis. 2020 Jun;20(6):631-3.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30190-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32213329?tool=bestpractice.com
新加坡研究人员发现,社交疏离措施(受感染个体隔离和家庭隔离检疫、学校停课和工作场所疏离)可显著减少模拟模型中的感染数量。[354]Koo JR, Cook AR, Park M, et al. Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study. Lancet Infect Dis. 2020 Jun;20(6):678-88.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30162-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32213332?tool=bestpractice.com
其危害亦应加以考虑。公共卫生政策主要依靠模型,而此类模型常忽略潜在危害,包括因经济损害、负向健康效应以及对脆弱人群的影响,而导致的过量死亡和不平等。[355]Bavli I, Sutton B, Galea S. Harms of public health interventions against covid-19 must not be ignored. BMJ. 2020 Nov 2;371:m4074.
https://www.bmj.com/content/371/bmj.m4074
http://www.ncbi.nlm.nih.gov/pubmed/33139247?tool=bestpractice.com
基于社区的大规模隔离所带来负面后果包括心理困扰、粮食危机、经济挑战、医疗可及性减少、不平等沟通加剧、以次充好的教育,以及基于性别的暴力。[356]Chu IY, Alam P, Larson H, et al. Social consequences of mass quarantine during epidemics: a systematic review with implications for the COVID-19 response. J Travel Med. 2020 Oct 13 [Epub ahead of print].
https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taaa192/5922349
http://www.ncbi.nlm.nih.gov/pubmed/33051660?tool=bestpractice.com
若干候选疫苗目前已通过临床实验获批进行人体实验,包括 mRNA 和 DNA 平台疫苗、腺病毒载体疫苗、刺突糖蛋白纳米颗粒疫苗和灭活病毒疫苗。[358]Mahase E. Covid-19: what do we know so far about a vaccine? BMJ. 2020 Apr 27;369:m1679.
https://www.bmj.com/content/369/bmj.m1679
俄罗斯在 8 月初成为全球第一个批准疫苗使用的国家。[359]Burki TK. The Russian vaccine for COVID-19. Lancet Respir Med. 2020 Sep 4 [Epub ahead of print].
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30402-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32896274?tool=bestpractice.com
但是,到目前为止,仅公布了 1/2 期结果(76 名参与者)。[360]Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020 Sep 3 [Epub ahead of print].
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31866-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32896291?tool=bestpractice.com
既往冠状病毒疫苗试验将细胞免疫病理学和抗体依赖性增强作用(antibody-dependent enhancement, ADE)视为潜在的安全问题,因此,SARS-CoV-2 的 ADE 由于先前暴露于其他冠状病毒(例如引起普通感冒的那些)而受到关注。[361]Padron-Regalado E. Vaccines for SARS-CoV-2: lessons from other coronavirus strains. Infect Dis Ther. 2020 Apr 23;:1-20.
https://link.springer.com/article/10.1007/s40121-020-00300-x
http://www.ncbi.nlm.nih.gov/pubmed/32328406?tool=bestpractice.com
[362]Hotez PJ, Corry DB, Bottazzi ME. COVID-19 vaccine design: the Janus face of immune enhancement. Nat Rev Immunol. 2020 Jun;20(6):347-8.
https://link.springer.com/article/10.1007/s40121-020-00300-x
http://www.ncbi.nlm.nih.gov/pubmed/32346094?tool=bestpractice.com
来自动物和人体研究的初步结果现已公布,但科学家呼吁对此结果保持谨慎。[363]Callaway E. Coronavirus vaccine trials have delivered their first results - but their promise is still unclear. Nature. 2020 May;581(7809):363-4.
https://www.nature.com/articles/d41586-020-01092-3
http://www.ncbi.nlm.nih.gov/pubmed/32433634?tool=bestpractice.com
亦存在担忧,当前 3 期临床试验可能无法产生严重结局(例如收治入院、给予危重症诊疗或死亡)减少的预期效果,或得出疫苗可以阻断病毒传播的结论–这在疫苗效能评估试验研究中,是两个关键性主要终点。[364]Doshi P. Will covid-19 vaccines save lives? Current trials aren't designed to tell us. BMJ. 2020 Oct 21;371:m4037.
https://www.bmj.com/content/371/bmj.m4037
http://www.ncbi.nlm.nih.gov/pubmed/33087398?tool=bestpractice.com
Ad5-nCoV:表达 SARS-CoV-2 穗状糖蛋白的重组 5 型腺病毒(adenovirus type-5, Ad5)载体疫苗。来自一项中国单中心开放性非随机剂量递增的 1 期临床试验的结果报告,该疫苗具有免疫原性,可诱导多数受试者体液应答(免疫接种后 28 日达到峰值)和 T 细胞应答(免疫接种后 14 日达到峰值)。受试者健康,且无基础疾病。在接种疫苗后最初 7 日内,83%(低剂量和中剂量组)和 75%(高剂量组)的受试者报告了至少一种不良反应。报告的最常见不良反应包括注射部位反应、发热、乏力、头痛和肌痛。接种后 28 日内未发现严重不良事件。[365]Zhu FC, Li YH, Guan XH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020 Jun 13;395(10240):1845-54.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32450106?tool=bestpractice.com
在对约 500 名健康成人(男性占 50%,平均年龄 39 岁)进行的一项 2 期随机、双盲、安慰剂对照试验研究发现,该疫苗单剂接种后(不论是 1x10¹¹ 病毒颗粒剂量亦或是 5x10¹⁰ 病毒颗粒剂量),大多数患者即可产生明显免疫反应。或第28天的5x10 15病毒颗粒剂量。与安慰剂组相比,Ad5-nCoV 组不良反应显著增多,1x10¹¹ 病毒颗粒剂量组中有 72% 受试者报道不良反应,而在 5x10¹⁰ 病毒颗粒剂量组中有 74% 受试者报道不良反应。[366]Zhu FC, Guan XH, Li YH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020 Jul 20 [Epub ahead of print].
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32702299?tool=bestpractice.com
AZD1222(之前称为 ChAdOx1 nCoV-19):一种携带 SARS-CoV-2 穗突蛋白的腺病毒载体疫苗。动物研究初步结果(未经同行评议)发现,单剂量可引起小鼠和恒河猴的体液和细胞应答。然而,尽管与未接种疫苗的动物相比,接种动物的支气管肺泡灌洗液和肺组织中的病毒载量显著降低,但未观察到经鼻病毒脱落减少。[367]van Doremalen N, Lambe T, Spencer A, et al. ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRxiv. 2020 May 13 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241103/
http://www.ncbi.nlm.nih.gov/pubmed/32511340?tool=bestpractice.com
使用脑膜炎球菌结合疫苗作为对照的年轻健康志愿者 1/2 期单盲随机对照试验发现,AZD1222 具有免疫原性。AZD1222 组中,局部和全身反应更为常见,接种疫苗后 28 天内未见严重不良事件报道。[368]Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020 Jul 20;:.
https://www.doi.org/10.1016/S0140-6736(20)31604-4
http://www.ncbi.nlm.nih.gov/pubmed/32702298?tool=bestpractice.com
英国进行的这项 III 期试验于九月初被叫停了,因为一名参与疫苗试验的被试出现了原因不明的病症。[369]AstraZeneca. Statement on AstraZeneca Oxford SARS-CoV-2 vaccine, AZD1222, COVID-19 vaccine trials temporary pause. 2020 [internet publication].
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/statement-on-astrazeneca-oxford-sars-cov-2-vaccine-azd1222-covid-19-vaccine-trials-temporary-pause.html
新闻报道表明,该受试者出现了横贯性脊髓炎,这是几乎所有疫苗都有报道的一种严重不良事件。 经英国药物和医疗产品监管署(Medicines and Healthcare products Regulatory Agency, MHRA)确认其安全性后,这项试验目前已于英国重开。该公司尚未揭示这一不良事件的性质。[370]AstraZeneca. COVID-19 vaccine AZD1222 clinical trials resumed in the UK. 2020 [internet publication].
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/covid-19-vaccine-azd1222-clinical-trials-resumed-in-the-uk.html
现在,包括美国在内的所有国家都开始进行试验。
灭活的 SARS-CoV-2 病毒(Sinovac®):包含更传统的化学灭活病毒。发现该疫苗可诱导小鼠、大鼠和非人类灵长类动物免疫力。当受到病毒攻击时,接种最高剂量疫苗的猴未发生感染,并且未在咽喉、肺或直肠中发现病毒。[371]Gao Q, Bao L, Mao H, et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020 Jul 3;369(6499):77-81.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202686/
http://www.ncbi.nlm.nih.gov/pubmed/32376603?tool=bestpractice.com
对两项进行中的 18 至 59 岁健康成人随机对照试验,和 96 名受试者 1 期试验及 224 名受试者 2 期试验所做期中分析提示,疫苗在 14 天内诱导了中和抗体应答。研究将疫苗与明矾佐剂进行了比较。注射后 7 天内所有参与者不良反应发生率为 15%,最常见者为注射部位反应和发热。尽管疫苗引发了抗体反应,但尚不清楚其是否可以保护个体免遭 COVID-19 侵袭。[372]Xia S, Duan K, Zhang Y, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA. 2020 Aug 13 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2769612
http://www.ncbi.nlm.nih.gov/pubmed/32789505?tool=bestpractice.com
mRNA-1273:一种新型疫苗,使用既往未获批用于人类的 mRNA 技术。该 mRNA 编码 SARS-CoV-2 全长融合前稳态刺突蛋白,包裹于脂质纳米颗粒中。1 期试验结果表明所有给予疫苗两剂(25、100 或 250 μg)接种(两剂间隔 28 天)的 45 位健康成人(年龄 18-55 岁)首次给药后第 15 天前出现血清转化。第 2 次疫苗接种后,所有剂量组抗体水平达到恢复期血清最高四分位数。全身性不良事件在第 2 次疫苗接种后发生频率更高,25 μg 组受试者达 54%,100 μg 和250 μg 组受试者则为 100%。接受最高剂量(250 μg)的 14 名患者中,21% 受试者在第 2 剂之后出现了一次或多次严重不良事件。25 μg 组一名受试者第一次疫苗接种后出现相关一过性荨麻疹,而退出试验。该研究不包括存在基础疾病者。[373]Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2: preliminary report. N Engl J Med. 2020 Jul 14 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMoa2022483
http://www.ncbi.nlm.nih.gov/pubmed/32663912?tool=bestpractice.com
mRNA-1273 疫苗已获得 FDA 授予的快速通道审批资格,III 期试验已启动。一项针对老年人的 I 期试验已完成。[374]Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020 Sep 29 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMoa2028436
http://www.ncbi.nlm.nih.gov/pubmed/32991794?tool=bestpractice.com
NVX-CoV2373:一种由全长三聚体 SARS-CoV-2 棘突糖蛋白和 Matrix-M1® 佐剂(基于从 石碱木提取出的皂苷)组成的重组 SARS-CoV-2 纳米颗粒疫苗。澳大利亚一项纳入了 131 名健康成人(18-59 岁)的 I/II 期随机安慰剂对照试验发现比起 COVID-19 恢复期血清,NVX-CoV2373 在 35 天时引发了更高水平的免疫应答。[375]Keech C, Albert G, Cho I, et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. 2020 Sep 2 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMoa2026920
http://www.ncbi.nlm.nih.gov/pubmed/32877576?tool=bestpractice.com
一项 III 期试验已启动。
BNT162b1/BNT162b2:一种脂质纳米颗粒配制,经核苷修饰的 mRNA 疫苗,可编码刺突糖蛋白 RBD。18 至 55 岁健康成人的 1/2 期研究已发表。两剂给药后 28 天,在所有受试者中均检测出 RBD 结合免疫球蛋白 G 抗体和 SARS-CoV-2 中和抗体。不良反应呈剂量依赖性,接受 10 μg 或 30 μg 剂量的受试者有 50% 报告不良反应,接受 100 μg 剂量的受试者有 58% 报告不良反应。[376]Mulligan MJ, Lyke KE, Kitchin N, et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. 2020 Aug 12 [Epub ahead of print].
https://www.nature.com/articles/s41586-020-2639-4
http://www.ncbi.nlm.nih.gov/pubmed/32785213?tool=bestpractice.com
BNT162b1 和 BNT162b2 在年轻成人(18 至 55 岁)和高龄(65 至 85 岁)成人 1 期试验中的结果亦已发布。[377]Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020 Oct 14 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMoa2027906
http://www.ncbi.nlm.nih.gov/pubmed/33053279?tool=bestpractice.com
BNT162b1 和 BNT162b2(其相关性候选疫苗)已获得 FDA 快速通道审批资格。BNT162b2 的全球 2/3 期试验已启动,并已获得批准,可招募 12 岁以下儿童。
JNJ-78436735(既往称为 Ad26.COV2.S):一种单价疫苗,由重组、无复制能力的 26 型腺病毒(Ad26)载体构成,构建为 SARS-CoV-2 刺突蛋白编码。该疫苗目前正在进行 3 期试验。由于未予披露的严重不良事件,该试验予以暂停,但目前已恢复进行。[378]Johnson & Johnson. Johnson & Johnson temporarily pauses all dosing in our Janssen COVID-19 vaccine candidate Clinical Trials. 2020 [internet publication].
https://www.jnj.com/our-company/johnson-johnson-temporarily-pauses-all-dosing-in-our-janssen-covid-19-vaccine-candidate-clinical-trials
其他候选疫苗的结果正逐步获取;但是,对于所有候选疫苗的详细讨论均超出本专题范围。
FDA 已对疫苗开发者颁布指南,要求其证明候选疫苗主要疗效终点的点估计在安慰剂对照试验中至少达到 50%,且统计学成功标准应为围绕主要疗效终点的适当 α-调整可信区间下限点估计 >30%。[379]US Food and Drug Administration. Development and licensure of vaccines to prevent COVID-19. 2020 [internet publication].
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19