疫苗
疫苗在多个国家获得了临时性紧急使用授权或有条件上市授权加以使用。
免疫计划通常优先考虑罹患重症或死亡风险最高者(例如疗养院居住者和员工、老年人、医务工作者以及伴基础疾患者)。但是,不同国家优先政策有所不同,因此应参考当地指南。
疫苗是否可预防无症状感染,亦或可对虽接受疫苗接种但仍遭感染者形成传播防护,尚不清楚。疫苗接种者应继续遵守一切公共卫生建议。疫苗接种后超过 2 个月时间的安全性和有效性(包括免疫力持续时间)尚未明确。 随着疫苗接种对病毒传播的影响,以及对社区的间接保护进行评估,建议将得到更新。[324]Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-15.
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
http://www.ncbi.nlm.nih.gov/pubmed/33301246?tool=bestpractice.com
[325]Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021 Feb 4;384(5):403-16.
https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
http://www.ncbi.nlm.nih.gov/pubmed/33378609?tool=bestpractice.com
[326]World Health Organization. Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BNT162b2-2021.1
[327]World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance. 2021 [internet publication].
https://www.who.int/publications/i/item/interim-recommendations-for-use-of-the-moderna-mrna-1273-vaccine-against-covid-19
[328]World Health Organization. Interim recommendations for use of the AZD1222 (ChAdOx1-S (recombinant)) vaccine against COVID-19 developed by Oxford University and AstraZeneca. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-AZD1222-2021.1
在美国,疾病预防控制中心建议,接种疫苗者暴露于 COVID-19 患者后,无需进行隔离检疫,前提是其符合以下标准:已接受两剂疫苗接种,且第二剂给药后至少已经过 2 周;处于最后一剂接种后 3 个月之内;且暴露后未出现 COVID-19 症状。[329]Centers for Disease Control and Prevention. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. 2021 [internet publication].
https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
不良事件监测极其重要,其可揭示临床试验中未发现的,发生率较低的其他严重不良事件。
例如,由于与发作性睡病具有相关性,2009-2010 年猪流感大流行期间使用的 Pandemrix® 疫苗已撤出市场。[330]Doshi P. Pandemrix vaccine: why was the public not told of early warning signs? BMJ. 2018 Sep 20;362:k3948.
新授权的 mRNA 疫苗既往未被批准用于人类,因此,这些类型疫苗暂缺乏安全性和有效性长期数据。
实验室确诊的 COVID-19 病例已见诸免疫接种后报道。接种疫苗后最初数天,症状可能会被误认为疫苗相关性不良反应。对患者报告症状保持高度怀疑,避免将其主诉误认为疫苗相关性反应,直到接种者接受检测并排除真性感染。[331]Amit S, Beni SA, Biber A, et al. Post-vaccination COVID-19 among healthcare workers, Israel. Emerg Infect Dis. 2021 Feb 1;27(4).
https://wwwnc.cdc.gov/eid/article/27/4/21-0016_article
http://www.ncbi.nlm.nih.gov/pubmed/33522478?tool=bestpractice.com
所有可疑不良反应都应通过英国黄卡系统进行报告。
Yellow Card: coronavirus (COVID-19)
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所有可疑不良反应都应通过美国疫苗不良事件报告系统(Vaccine Adverse Event Reporting System, VAERS)进行汇报。
Vaccine Adverse Event Reporting System
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各地区疫苗给药计划可有所不同。
延长两剂药物接种间隔时间、减少给药次数、改变剂量(半衰期),或混合和匹配不同的 COVID-19 疫苗等建议均曾被提出。但是,对于此类接种策略尚无临床证据予以支持。[332]US Food and Drug Administration. FDA statement on following the authorized dosing schedules for COVID-19 vaccines. 2021 [internet publication].
https://www.fda.gov/news-events/press-announcements/fda-statement-following-authorized-dosing-schedules-covid-19-vaccines
世界卫生组织(World Health Organization, WHO)建议,处于特殊流行环境的国家,可考虑较短时间延迟第二剂 mRNA 疫苗给药(根据目前已获得的临床试验数据,最多延迟 42 天),以此作为务实方法,在疫苗供应持续走高时,使最大数量个体获益于第一剂接种。然而,此类扩展用药的证据却并不强。各国应确保对给药间隔进行的所有此类计划性调整,均不影响接受第二剂接种可能性。WHO 不支持改变剂量。[326]World Health Organization. Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BNT162b2-2021.1
[327]World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance. 2021 [internet publication].
https://www.who.int/publications/i/item/interim-recommendations-for-use-of-the-moderna-mrna-1273-vaccine-against-covid-19
在英国,疫苗接种和免疫联合委员会建议,相比第二剂给药,任何疫苗的首剂给药,应首先尽可能多的给予候选接种者。[333]Department of Health & Social Care. Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020. 2021 [internet publication].
https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020/joint-committee-on-vaccination-and-immunisation-advice-on-priority-groups-for-covid-19-vaccination-30-december-2020
[334]Department of Health & Social Care. Optimising the COVID-19 vaccination programme for maximum short-term impact. 2021 [internet publication].
https://www.gov.uk/government/publications/prioritising-the-first-covid-19-vaccine-dose-jcvi-statement/optimising-the-covid-19-vaccination-programme-for-maximum-short-term-impact
但是,延长首剂和第二剂接种之间的给药间隔,缺乏证据支持,其不在制造商获批的给药建议范围之内。[335]Iacobucci G, Mahase E. Covid-19 vaccination: what's the evidence for extending the dosing interval? BMJ. 2021 Jan 6;372:n18.
https://www.bmj.com/content/372/bmj.n18
http://www.ncbi.nlm.nih.gov/pubmed/33408068?tool=bestpractice.com
在美国,疾病预防控制中心建议,如果无法达到建议给药间隔,则可在首剂给药后 6 周内,安排第二剂 mRNA 疫苗给药。该机构继续强调第二剂接种应尽可能贴近建议的时间间隔,并指出已在美国应用的两种 mRNA 疫苗在特殊情况下可考虑互换。[329]Centers for Disease Control and Prevention. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. 2021 [internet publication].
https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
英国已开始进行临床试验,明确不同疫苗是否可采用 2 剂给药方案。[336]Department of Health and Social Care. World-first COVID-19 alternating dose vaccine study launches in UK. 2021 [internet publication].
https://www.gov.uk/government/news/world-first-covid-19-alternating-dose-vaccine-study-launches-in-uk
接种疫苗之前,需参考当地指南。接种疫苗之前,须获得患者自由和自愿的知情同意。[337]Public Health England. Consent: the green book, chapter 2. 2013 [internet publication].
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/144250/Green-Book-Chapter-2-Consent-PDF-77K.pdf
下表对于已在诸多国家获准使用的三种主要疫苗进行了比较。
除此以外,CoronaVac® 和 Sinopharm®(严重急性呼吸综合征冠状病毒 2 [severe acute respiratory syndrome coronavirus 2, SARS-CoV-2]病毒灭活版本)已在中国获得使用授权,而 SputnikV®(腺病毒载体疫苗)已在俄罗斯获得使用授权,有效率为 91.6%。[338]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 26;396(10255):887-97.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32896291?tool=bestpractice.com
其他若干候选疫苗仍在进行研发,包括 mRNA 疫苗、DNA 疫苗、病毒载体疫苗、蛋白亚基疫苗、减毒活疫苗、病毒灭活疫苗和鼻内给药系统。[339]Jeyanathan M, Afkhami S, Smaill F, et al. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020 Oct;20(10):615-32.
https://www.nature.com/articles/s41577-020-00434-6
http://www.ncbi.nlm.nih.gov/pubmed/32887954?tool=bestpractice.com
WHO: draft landscape of COVID-19 candidate vaccines
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| 辉瑞/BioNTech COVID-19 疫苗 | Moderna COVID-19 疫苗 | 阿斯利康 COVID-19 疫苗 |
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同义命名 | COVID-19 mRNA 疫苗 BNT162b2 | COVID-19 疫苗 mRNA-1273 | COVID-19 重组疫苗 ChAdOx1 S |
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疫苗类型 | 脂质纳米颗粒配制的 mRNA 疫苗,可编码 SARS-CoV-2 刺突蛋白 | 携带 SARS-CoV-2 刺突蛋白基因编码的腺病毒(黑猩猩)载体疫苗 |
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有效性* | 95% | 94% | 70% |
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获批 | 英国、美国、欧洲、加拿大 | 英国、美国、欧洲 | 英国、欧洲 |
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适应症 | ≥16 岁者主动免疫 | ≥18 岁者主动免疫 |
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获批剂量* | 两次给药治疗方案 0.3 mL(30 μg)肌内注射;第二剂给药至少在首剂给药后 21 天 | 两次给药治疗方案 0.5 mL(100 μg)肌内注射;第二剂给药至少在首剂给药后 28 天 | 两次给药治疗方案 0.5 mL 肌内注射(5 × 1010 病毒颗粒);首剂给药后 4-12 周 给予第二剂 |
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禁忌证 | 对活性物质或任何赋形剂发生超敏反应;对首剂接种立即产生过敏反应(不应再给予第二剂接种) |
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注意事项 | 全身过敏反应/过敏反应病史 急性重度热性疾病 出血性疾病或抗凝 免疫受损 妊娠和哺乳 既往使用 COVID-19 单克隆抗体或血浆进行治疗 | 全身过敏反应/过敏反应病史 急性重度热性疾病 出血性疾病或抗凝 免疫受损 妊娠和哺乳 |
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不良事件* | 常见:头痛;关节痛;肌痛;注射部位反应;乏力;发热;寒战;恶心 不常见:淋巴结肿大;周身不适;全身过敏反应;超敏反应;急性周围性面神经麻痹 | 常见:头痛;关节痛;肌痛;注射部位反应;乏力;发热;畏寒;恶心;呕吐;腹泻;皮疹;淋巴结肿大 不常见:周身不适;急性周围性面神经麻痹;超敏反应;面部水肿(若有面部填充物) | 常见:头痛;关节痛;肌痛;注射部位反应;乏力;周身不适;发热;寒战;恶心;呕吐;流行性感冒样疾病 不常见:淋巴结肿大;头晕;食欲下降;腹痛;多汗;瘙痒;皮疹;神经炎性疾患 |
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相互作用 | 与其他疫苗/药物的相互作用尚未进行研究(WHO 建议接种 COVID-19 疫苗和其他疫苗时,至少间隔 14 天) |
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医疗卫生专业人士信息 |
Pfizer/BioNTech COVID-19 vaccine
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Moderna COVID-19 vaccine
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AstraZeneca COVID-19 vaccine
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特定获批 COVID-19 疫苗比较。数据在不断变化;查阅当地药物处方集或指南,获取您所在地区详细信息。*参阅以下疫苗有效性数据和疫苗安全性数据章节,获取更多信息。**给药计划可在部分地区有所不同。最近审核/更新:2021 年 2 月 17 日。
疫苗和全身过敏反应或血管迷走神经反应
疫苗接种后,在一般人群中,临床试验之外已见严重过敏反应报道,包括全身过敏反应。
在美国,截至 2021 年 1 月 18 日,通过 VAERS 进行的监测发现,每百万剂辉瑞/BioNTech 疫苗出现 4.7 例过敏反应,每百万剂 Moderna 疫苗出现 2.5 例过敏反应。[340]Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA COVID-19 vaccines in the US: December 14, 2020 – January 18, 2021. JAMA. 2021 Feb 12 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2776557
http://www.ncbi.nlm.nih.gov/pubmed/33576785?tool=bestpractice.com
在英国,截至 2021 年 1 月 31 日,对黄卡报告系统的监测发现 103 例使用辉瑞/BioNTech 疫苗产生的过敏反应(每 10 万剂 1-2 例),以及 30 例使用阿斯利康疫苗产生的过敏反应。[341]Medicines and Healthcare products Regulatory Agency. Coronavirus vaccine: weekly summary of Yellow Card reporting. 2021 [internet publication].
https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting
mRNA 疫苗接种后反应被提出可能是由于脂质聚乙二醇(pegylated ethylene glycol, PEG)或 PEG 衍生物(例如聚山梨酸酯)的存在所致。[342]Castells MC, Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. N Engl J Med. 2020 Dec 30 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMra2035343
http://www.ncbi.nlm.nih.gov/pubmed/33378605?tool=bestpractice.com
WHO 提出建议,所有对疫苗成分具有全身过敏反应病史者,对所有疫苗均存在免疫接种禁忌。对第一剂给药立即出现全身性过敏反应者不应再接受其他剂次给药。疫苗给药应仅在全身过敏反应可得以处理的机构进行,接种后应至少观察 15 分钟。[326]World Health Organization. Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BNT162b2-2021.1
[327]World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance. 2021 [internet publication].
https://www.who.int/publications/i/item/interim-recommendations-for-use-of-the-moderna-mrna-1273-vaccine-against-covid-19
[328]World Health Organization. Interim recommendations for use of the AZD1222 (ChAdOx1-S (recombinant)) vaccine against COVID-19 developed by Oxford University and AstraZeneca. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-AZD1222-2021.1
WHO 建议,首剂 mRNA 疫苗接种后立即产生非全身过敏性过敏反应者(即给药后 4 小时内出现荨麻疹、血管性水肿或呼吸道症状 [例如咳嗽、喘鸣或喘息]),不应再接受其他剂次接种,除非具有专科知识技能的医疗卫生专业人士进行分析后予以推荐。对任何其他疫苗或注射治疗出现即时过敏反应病史,均应被考虑为一种警示,但并非疫苗接种禁忌症。进行风险评估,确定反应类型和严重性,以及信息可靠性。此类人群仍可接种疫苗,但应对疫苗接种风险和获益进行权衡,接种者在给药后 30 分钟应留观于医疗机构,从而使全身过敏反应可得到立即处理。无严重过敏反应史者,亦有全身过敏反应报道。食物性、昆虫毒液、接触性或季节性过敏,以及过敏性鼻炎、湿疹和哮喘,不考虑为警示征象。对乳胶、鸡蛋或明胶过敏者,无疫苗接种禁忌症,无需采取预防措施。[326]World Health Organization. Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BNT162b2-2021.1
[327]World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance. 2021 [internet publication].
https://www.who.int/publications/i/item/interim-recommendations-for-use-of-the-moderna-mrna-1273-vaccine-against-covid-19
位于英国的药品和医疗产品监管署建议,对疫苗成分有过敏反应既往史者,均不应进行疫苗接种,但伴其他过敏史(例如食物过敏)者,可接种该疫苗。[343]Medicines and Healthcare products Regulatory Agency. Oxford University/AstraZeneca COVID-19 vaccine approved. 2020 [internet publication].
https://www.gov.uk/government/news/oxford-universityastrazeneca-covid-19-vaccine-approved
有过敏史或全身过敏史者,各地区指南对其疫苗接种可有所不同;查询当地指南。
具有接受皮肤填充剂病史者,注射 mRNA 疫苗后可能在填充剂注射部位(例如唇面部)或其附近区域出现肿胀。这似乎呈暂时性,可用皮质类固醇予以处理。
注射部位周围迟发型局部反应已见诸报道,有时该反应十分显著。[329]Centers for Disease Control and Prevention. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. 2021 [internet publication].
https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
焦虑相关性反应,包括血管迷走神经反应和过度通气。确保采取适当的预防措施,避免因晕厥受伤。
疫苗和特定患者群
临床试验关于特定患者群使用疫苗的数据很少或无数据。尽管如此,基于所使用的疫苗,WHO 仍建议以下人群可进行疫苗接种:[326]World Health Organization. Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BNT162b2-2021.1
[327]World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance. 2021 [internet publication].
https://www.who.int/publications/i/item/interim-recommendations-for-use-of-the-moderna-mrna-1273-vaccine-against-covid-19
[328]World Health Organization. Interim recommendations for use of the AZD1222 (ChAdOx1-S (recombinant)) vaccine against COVID-19 developed by Oxford University and AstraZeneca. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-AZD1222-2021.1
建议对伴急性发热性疾病或当前急性 COVID-19 患者(除非其已无发热表现,且已自急症中得以恢复),以及既往曾接受 COVID-19 被动抗体治疗患者,延迟进行疫苗接种。对于过去 6 个月确诊 SARS-CoV-2 感染的人群,可考虑延迟疫苗接种(直到本时期结束时)。
根据预印本研究,对于已存在固有免疫力者,第一剂 mRNA 疫苗接种后的抗体反应,等于或可能超过无固有免疫力者第二剂免疫接种后的效价。此类,既往感染 SARS-CoV-2 者反应原性显著升高。[344]Krammer F, Srivastava K, Simon V, et al. Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. medRxiv. 2021 Feb 1 [Epub ahead of print].
https://www.medrxiv.org/content/10.1101/2021.01.29.21250653v1.full.pdf
WHO 建议对预期寿命少于 3 个月的极脆弱老年人进行个体风险-获益评估。[327]World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance. 2021 [internet publication].
https://www.who.int/publications/i/item/interim-recommendations-for-use-of-the-moderna-mrna-1273-vaccine-against-covid-19
23 名患者接受辉瑞/BioNTech 疫苗接种不久后死亡,因此挪威药品管理局建议在进行疫苗接种前,对极端脆弱老年患者进行充分评估。但是,目前尚不清楚这部分死亡事件与疫苗之间是否存在关联。该机构迄今已对 13 例死亡病例进行调查,并得出结论,mRNA 疫苗常见不良反应,例如发热、恶心和腹泻,可能对部分脆弱患者产生致死结局具有贡献。[345]Norwegian Medicines Agency. Covid-19 vaccination associated with adverse drug reactions in elderly people who are frail. 2021 [internet publication].
https://legemiddelverket.no/nyheter/covid-19-vaccination-associated-with-deaths-in-elderly-people-who-are-frail
[346]Torjesen I. Covid-19: Norway investigates 23 deaths in frail elderly patients after vaccination. BMJ. 2021 Jan 15;372:n149.
https://www.bmj.com/content/372/bmj.n149
http://www.ncbi.nlm.nih.gov/pubmed/33451975?tool=bestpractice.com
疫苗和妊娠/哺乳期女性
疫苗有效性数据
辉瑞/BioNTech COVID-19 疫苗
有效性基于对 43,448 名参与者的 3 期试验结果中期分析得出(疫苗和安慰剂组以 1:1 比例随机分配)。16 岁及以上人群中,与安慰剂(生理盐水)相比,2 剂疫苗接种后,对有症状 COVID-19 预防有效性据称可达 95% 。该结论基于对 170 例接受第二剂接种后至少 7 天以上发病,目前及既往无 SARS-CoV-2 感染证据的 COVID-19 确诊病例所进行分析得出(疫苗组 8 例,安慰剂组 162 例)。首剂给药后,有效性为 52%。首剂给药后发病的 10 例重症中,安慰剂组有 9 例,疫苗组有 1 例。这仅为疫苗介导的重症保护提供了初步证据。[324]Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-15.
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
http://www.ncbi.nlm.nih.gov/pubmed/33301246?tool=bestpractice.com
初步研究表明,该疫苗可能对具有刺突蛋白突变的新 SARS-CoV-2 变体有效(即 B.1.1.7 和 B.1.351 谱系以及 N501Y 突变);然而,对于中和 B.1.351 变体可能较弱。[350]Xie X, Zou J, Fontes-Garfias CR, et al. Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv. 2021 Jan 7 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805448/
http://www.ncbi.nlm.nih.gov/pubmed/33442691?tool=bestpractice.com
[351]Muik A, Wallisch AK, Sänger B, et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. Science. 2021 Jan 29 [Epub ahead of print].
https://science.sciencemag.org/content/early/2021/01/28/science.abg6105.long
http://www.ncbi.nlm.nih.gov/pubmed/33514629?tool=bestpractice.com
[352]Xie X, Liu Y, Liu J, et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K, and N501Y variants by BNT162b2 vaccine-elicited sera. bioRxiv. 2021 Jan 27 [Epub ahead of print].
https://www.biorxiv.org/content/10.1101/2021.01.27.427998v1
http://www.ncbi.nlm.nih.gov/pubmed/33532771?tool=bestpractice.com
[353]Stamatatos L, Czartoski J, Wan YH, et al; medRxiv. Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1. 2021 [internet publication].
https://www.medrxiv.org/content/10.1101/2021.02.05.21251182v1
[354]Liu Y, Liu J, Xia H, et al. Neutralizing activity of BNT162b2-elicited serum: preliminary report. N Engl J Med. 2021 Feb 17 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMc2102017
http://www.ncbi.nlm.nih.gov/pubmed/33596352?tool=bestpractice.com
进一步研究有待开展。
Moderna COVID-19 疫苗
有效性基于对 30,420 名参与者的 3 期试验结果中期分析得出(疫苗和安慰剂组以 1:1 比例随机分配)。18 岁及以上人群中,与安慰剂(生理盐水)相比,2 剂疫苗接种后,对有症状 COVID-19 预防有效性据称可达 94.1% 。该结论基于对 196 例接受第二剂接种后至少 14 天以上发病,目前及既往无 SARS-CoV-2 感染证据的 COVID-19 确诊病例所进行分析得出(疫苗组 11 例,安慰剂组 185 例)。首剂给药后发病的 30 例重症中(包括 1 例死亡),所有病例均出现于安慰剂组,无病例出现于疫苗组。[325]Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021 Feb 4;384(5):403-16.
https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
http://www.ncbi.nlm.nih.gov/pubmed/33378609?tool=bestpractice.com
初步研究表明,该疫苗可能对具有刺突蛋白突变的新 SARS-CoV-2 变体有效(即 B.1.351 和 B.1.1.7 谱系)。尽管与早期 SARS-CoV-2 变体相比,B.1.351 变体的中和抗体滴度较低,但其水平预期仍具有保护性,然而这一点需加以证实。[353]Stamatatos L, Czartoski J, Wan YH, et al; medRxiv. Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1. 2021 [internet publication].
https://www.medrxiv.org/content/10.1101/2021.02.05.21251182v1
[355]Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv. 2021 Jan 25 [Epub ahead of print].
https://www.biorxiv.org/content/10.1101/2021.01.25.427948v1
http://www.ncbi.nlm.nih.gov/pubmed/33501442?tool=bestpractice.com
[356]Wu K, Werner AP, Koch M, et al. Serum neutralizing activity elicited by mRNA-1273 vaccine: preliminary report. N Engl J Med. 2021 Feb 17 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMc2102179
http://www.ncbi.nlm.nih.gov/pubmed/33596346?tool=bestpractice.com
进一步研究有待开展。制药商将对于额外加强剂量接种进行试验,研究对于新兴病毒株进一步提升中和抗体滴度,超过现有初步疫苗接种水平的能力。同时,其正在推动新兴变体加强型候选疫苗(即 B.1.351 谱系变体[称为 mRNA-1273.351])进入临床前试验和 1 期试验。[357]Moderna, Inc. Moderna COVID-19 vaccine retains neutralizing activity against emerging variants first identified in the UK and the Republic of South Africa. 2021 [internet publication].
https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against
阿斯利康 COVID-19 疫苗
有效性基于来自四项正在英国、巴西和南非开展,拥有 11,636 名参与者的随机对照临床试验总体数据中期分析得出。18 岁及以上人群中,与对照组(脑膜炎球菌疫苗或生理盐水)相比,2 剂疫苗接种后,对有症状 COVID-19 预防有效性据称可达 70.4%。该结论基于对 131 例接受第二剂接种后至少 15 天以上发病,目前及既往无 SARS-CoV-2 感染证据的 COVID-19 确诊病例所进行分析得出(疫苗组 30 例,安慰剂组 101 例)。试验结果有待发表。有效性和安全性数据目前局限于 ≥65 岁人群。[358]Medicines and Healthcare products Regulatory Agency. Information for healthcare professionals on COVID-19 vaccine AstraZeneca. 2021 [internet publication].
https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-healthcare-professionals-on-covid-19-vaccine-astrazeneca
当给药间隔更长时,疫苗效力似乎更高。一项预印本研究数据包括了对报道的 332 例有症状病例进行额外更多一个月数据采集。该研究发现,单次标准剂量给药在疫苗接种后的前 90 天内,对于症状性疾病总体可提供 76% 的保护性。在给药间隔为 12 周或更长时间的患者中,第二剂接种后,效力可达 82.4%。但是,如果两剂给药间隔短于 6 周,则效力仅为 54.9%。[359]Voysey M, Costa Clemens SA, Madhi SA, et al; SSRN. Single dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine. 2021 [internet publication].
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268
WHO 建议每剂给药间隔为 8 至 12 周。[328]World Health Organization. Interim recommendations for use of the AZD1222 (ChAdOx1-S (recombinant)) vaccine against COVID-19 developed by Oxford University and AstraZeneca. 2021 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-AZD1222-2021.1
一项预印本研究表明,该疫苗可能对 B.1.1.7 SARS-CoV-2 变体引发的症状性感染有效。[360]Emary KRW, Golubchik T, Aley PK, et al; SSRN. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 VOC 202012/01 (B.1.1.7). 2021 [internet publication].
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3779160
然而,疫苗在南非的推出已被叫停,因一项研究发现其对于 B.1.351 变体引发的轻中度疾病并未形成保护。[361]Mahase E. Covid-19: South Africa pauses use of Oxford vaccine after study casts doubt on efficacy against variant. BMJ. 2021 Feb 8;372:n372.
https://www.bmj.com/content/372/bmj.n372
http://www.ncbi.nlm.nih.gov/pubmed/33558207?tool=bestpractice.com
疫苗安全性数据
辉瑞/BioNTech COVID-19 疫苗
安全性基于对 43,448 名参与者 3 期试验结果中期分析得出。反应原性亚组包括 8183 名参与者。[324]Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-15.
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
http://www.ncbi.nlm.nih.gov/pubmed/33301246?tool=bestpractice.com
与安慰剂相比,疫苗组局部不良反应更为常见,最常见反应为注射后 7 天内出现注射部位疼痛(年轻参与者首剂给药后出现率为 83%,第二剂给药后为 78%;年长参与者首剂给药后出现率为 71%,第二剂给药后为 66%)。不到 1% 受试者诉称严重疼痛。首剂和第二剂接种后,局部不良反应相似。
与安慰剂相比,疫苗组全身不良反应更为常见,年轻患者和第二剂接种后不良反应发生率更高。第二剂给药后最常见报道全身不良反应为乏力(年轻参与者比例为 59%;老年参与者比例为 51%)、头痛(年轻参与者比例为 52%;老年参与者比例为 39%)和发热(年轻参与者比例为 16%;老年参与者比例为 11%)。除第二剂接种后出现乏力和头痛外,任一剂接种后,严重全身事件在参与者中的发生率,据报道 <2%。
其他罕见不良事件包括淋巴结肿大、肩关节损伤(与疫苗接种相关)、阵发性室性心律失常和右腿感觉异常。
Moderna COVID-19 疫苗
安全性基于对 30,420 名参与者 3 期试验结果中期分析得出。[325]Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021 Feb 4;384(5):403-16.
https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
http://www.ncbi.nlm.nih.gov/pubmed/33378609?tool=bestpractice.com
预设性局部或全身不良反应在疫苗组中见于 87.8% 首剂接种 7 天内的参与者,而在安慰剂组中其比例为 48%,在疫苗组中见于 92.2% 第二剂接种 7 天内的参与者,而在安慰剂组中其比例为 42.8%。报告的最常见预设性不良反应包括注射部位反应、乏力、头痛、肌痛和关节痛。此类反应在第二剂接种后更为常见且更为严重。相较于年龄 ≥65 岁成人,年龄在 18 至 64 岁之间的参与者预设性不良反应更为常见。
疫苗相关性非预设性不良事件(注射给药后 28 天内)在疫苗组中见于 8.2% 参与者,而在安慰剂组中见于 4.5% 患者。与安慰剂组相比,疫苗组严重不良事件发生率更高(0.5% 与 0.2%)。最常见的非预设性不良事件(见于至少 1% 参与者)为乏力和头痛。此类事件的相对发生率不受年龄影响。
与安慰剂组(1 例)相比,贝尔麻痹(3 例)更常见于疫苗组,提示其可能不仅仅是偶发事件。由于临床试验之外,更大范围人群需接种疫苗,因此需予以密切监测。
阿斯利康 COVID-19 疫苗
安全性基于来自四项正在英国、巴西和南非开展,拥有 23,745 名参与者的随机对照临床试验总体数据中期分析得出(试验结果尚未发布)。[358]Medicines and Healthcare products Regulatory Agency. Information for healthcare professionals on COVID-19 vaccine AstraZeneca. 2021 [internet publication].
https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-healthcare-professionals-on-covid-19-vaccine-astrazeneca
最常报道的不良事件为:注射部位反应(>60%);头痛、乏力(>50%);肌痛、周身不适(>40%);发热、寒战(>30%);关节痛、恶心(>20%)。在第二剂接种后,以及年龄 ≥65 岁成人,不良反应较轻,报告频次更低。
疫苗试验局限性
数据关键局限性在于安全性和有效性随访持续时间过短。试验不足以可靠的检测出较少见的不良事件,且中位随访时间在第二剂给药后仅 2 个月。试验未明确疫苗是否可防止传播或影响传染性,且保护力持续时间尚未确定。无儿童或青少年、孕妇或哺乳期女性,或免疫功能低下者数据。无数据对于重症高风险人群、既往 SARS-CoV-2 感染者有效性,以及对于疾病长期影响或死亡率等进行评估。[324]Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-15.
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
http://www.ncbi.nlm.nih.gov/pubmed/33301246?tool=bestpractice.com
[325]Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021 Feb 4;384(5):403-16.
https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
http://www.ncbi.nlm.nih.gov/pubmed/33378609?tool=bestpractice.com
当前临床试验存在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)减少预期效果的担忧,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。[362]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
而且,由于试验研究已经发布,关于最终效力数据排除等重要问题,以及有关镇痛和退热药物使用、盲目性消除和主要事件裁决委员会等担忧,已被提出。[363]Doshi P. Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data. BMJ Opinion. 2021 [internet publication].
https://blogs.bmj.com/bmj/2021/01/04/peter-doshi-pfizer-and-modernas-95-effective-vaccines-we-need-more-details-and-the-raw-data/
对于受试者的长期计划性随访在试验条件下不易进行,原因在于对接受安慰剂的患者,不给予疫苗接种而进行长期随访存在伦理问题。这可能会对正在进行的疫苗研究无形中构成威胁,其尚未对 COVID-19 免疫学相关性保护做出定义,它可因疫苗平台、个体特征、年龄群组和人群亚组而各异。[364]Singh JA, Upshur REG. The granting of emergency use designation to COVID-19 candidate vaccines: implications for COVID-19 vaccine trials. Lancet Infect Dis. 2020 Dec 8 [Epub ahead of print].
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30923-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33306980?tool=bestpractice.com
[365]WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation; Krause PR, Fleming TR, Longini IM, et al. Placebo-controlled trials of Covid-19 vaccines: why we still need them. N Engl J Med. 2021 Jan 14;384(2):e2.
https://www.nejm.org/doi/full/10.1056/NEJMp2033538
http://www.ncbi.nlm.nih.gov/pubmed/33264543?tool=bestpractice.com
[366]Rid A, Lipsitch M, Miller FG. The ethics of continuing placebo in SARS-CoV-2 vaccine trials. JAMA. 2021 Jan 19;325(3):219-20.
https://jamanetwork.com/journals/jama/fullarticle/2774382
http://www.ncbi.nlm.nih.gov/pubmed/33315080?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。SARS-CoV-2 的 ADE 由于疫苗接种之后,后续暴露于野生型 SARS-CoV-2,以及先前暴露于其他冠状病毒(例如引起普通感冒者)而受到关注。[367]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
[368]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
现有数据并未表明使用 mRNA 疫苗存在出现疫苗增强疾病(vaccine-enhanced disease)的风险;但是数据有限,随时间进展(可能与免疫力下降有关)的风险仍未明确,需行进一步评估。[324]Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-15.
https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
http://www.ncbi.nlm.nih.gov/pubmed/33301246?tool=bestpractice.com
[325]Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021 Feb 4;384(5):403-16.
https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
http://www.ncbi.nlm.nih.gov/pubmed/33378609?tool=bestpractice.com
医疗卫生专业人士感染防控
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。[369]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:[369]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:[369]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。[369]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。[369]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 SARS-CoV-2 分子和血清学检测均为阴性。[370]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。[371]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:
初级医疗保健医生的远程医疗
重要的是,初级医疗保健医生应尽可能避免对初级医疗保健中疑似 COVID-19 患者进行面对面评估,以避免感染。[372]Razai MS, Doerholt K, Ladhani S, et al. Coronavirus disease 2019 (covid-19): a guide for UK GPs. BMJ. 2020 Mar 5;368:m800.
https://www.bmj.com/content/368/bmj.m800.long
http://www.ncbi.nlm.nih.gov/pubmed/32144127?tool=bestpractice.com
多数患者可通过电话或视频咨询,进行远程管理。针对此类患者有处理流程:
普通公众一般性预防措施
社区环境中使用口罩
社区环境中使用口罩的建议因国家而异。[376]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。参阅当地公共卫生指南,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。有效性数据基于有限且一致性欠缺的观察性研究和流行病学研究。[87]World Health Organization. Mask use 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
首个对于口罩在社区中使用有效性进行调查的随机对照试验(除了其他公共卫生措施,例如社会隔离)发现,与不给予口罩佩戴建议相比,出门在外时佩戴外科口罩的建议,并未减少 SARS-CoV-2 感染发生率。然而,对于口罩是否可以减少从口罩佩戴者到他人的疾病传播,该研究并未进行评估。[377]Bundgaard H, Bundgaard JS, Raaschou-Pedersen DET, et al. Effectiveness of adding a mask recommendation to other public health measures to prevent SARS-CoV-2 infection in Danish mask wearers: a randomized controlled trial. Ann Intern Med. 2020 Nov 18 [Epub ahead of print].
https://www.acpjournals.org/doi/10.7326/M20-6817
http://www.ncbi.nlm.nih.gov/pubmed/33205991?tool=bestpractice.com
一份 Cochrane 评价发现,佩戴口罩对流感样疾病感染人数影响不大,甚至无影响;但是,此结论基于低确定性证据,并且不包括当前 COVID-19 大流行研究结果。[378]Jefferson T, Del Mar CB, Dooley L, et al. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database Syst Rev. 2020 Nov 20;(11):CD006207.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006207.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/33215698?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 感染对比有效性的直接证据不足。[379]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 Oct 6;173(7):542-55.
https://www.acpjournals.org/doi/10.7326/M20-3213
http://www.ncbi.nlm.nih.gov/pubmed/32579379?tool=bestpractice.com
[380]Chou R, Dana T, Jungbauer R, et al. Update alert 4: masks for prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings. Ann Intern Med. 2020 Dec 29 [Epub ahead of print].
https://www.acpjournals.org/doi/10.7326/L20-1429
http://www.ncbi.nlm.nih.gov/pubmed/33370171?tool=bestpractice.com
随机试验尚未解决源头控制问题。
尽管缺乏高质量证据,但 WHO 建议,已知或怀疑存在社区传播或聚集性传播区域,以下环境中应佩戴非医用口罩:无法保持躯体疏离的室内或室外;无论是否可以保持躯体疏离,通风不足的室内环境;以及无法保持躯体疏离,且患者出现严重并发症风险升高时(例如高龄、基础疾病)。照护者和与疑似或确诊病例同居者,无论病例是否有症状,均应佩戴医用口罩。5 岁以下儿童无需佩戴口罩,从而节省资源。6 至 11 岁儿童建议基于风险采用防护方法。对于免疫功能低下儿童,或患有特定疾病、发育障碍或残障儿童,需加以特别考虑。WHO 建议,进行剧烈体力活动时勿佩戴口罩。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。[87]World Health Organization. Mask use 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。[87]World Health Organization. Mask use 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。[381]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。[382]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。[383]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
酒精类手消毒制剂
CDC 已发布一项关于含甲醇(可能被标记为含有乙醇)的酒精类消毒剂警告。出现相关症状和征象(例如头痛、视力损害、恶心/呕吐、腹痛、运动失调、意识水平下降)的患者,如果他们摄入了手消毒剂或频繁局部外用药物,应对甲醇中毒加以考虑。永久性失明和死亡病例已见诸报道。[384]Centers for Disease Control and Prevention. Serious adverse health events associated with methanol-based hand sanitizers. 2020 [internet publication].
https://emergency.cdc.gov/han/2020/han00434.asp
频繁使用手部消毒剂可导致细菌耐药。曾有意外食用和非故意性眼部暴露的报道,尤其是儿童。[385]Mahmood A, Eqan M, Pervez S, et al. COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways. Sci Total Environ. 2020 Jun 27;742:140561.
https://www.sciencedirect.com/science/article/pii/S0048969720340833?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/32623176?tool=bestpractice.com
[386]Martin GC, Le Roux G, Guindolet D, et al. Pediatric eye injuries by hydroalcoholic gel in the context of the coronavirus disease 2019 pandemic. JAMA Ophthalmol. 2021 Jan 21 [Epub ahead of print].
https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2775155
http://www.ncbi.nlm.nih.gov/pubmed/33475712?tool=bestpractice.com
旅行相关性感染控制措施
诸多国家已实施旅行相关性管控措施,包括完全封闭边界、施行部分旅行限制、出入境筛查和/或隔离旅客。总体而言,极低等到低等证据表明,旅行相关性管控措施可能有助于限制感染跨境传播。跨境旅行限制可能比出入境筛查更有效,并且与其他措施(例如隔离、观察)相结合,筛查可能更为有效。[387]Burns J, Movsisyan A, Stratil JM, et al. Travel‐related control measures to contain the COVID‐19 pandemic: a rapid review. Cochrane Database Syst Rev. 2020 Sep 16:CD013717.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013717/full
出/入境筛查:对于到过高感染风险地区者,可通过关于其旅行、患病者接触、感染症状和/或体温测量的问卷进行筛查。低确定性证据表明,在旅行枢纽进行筛查可能会稍微减缓感染病例输入;但是,证据基础来自两项数学模型研究,因而受到其假设性限制。有证据表明,对看似明显健康者进行一次性筛查,可能漏诊 40% 至 100% 感染者,但该结论的确定性为极低至中等。在患病率极低的环境中,对症状或体温进行筛查,可能会产生极少的假阴性和许多真阴性,但总体准确性较低。反复进行筛查最终可能导致更多病例被发现,并减少假阳性或假阴性带来的影响。[388]Viswanathan M, Kahwati L, Jahn B, et al. Universal screening for SARS‐CoV‐2 infection: a rapid review. Cochrane Database Syst Rev. 2020 Sep 15:CD013718.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013718/full
2020 年 1 月至 2020 年 9 月期间,美国三大主要机场入境筛查中,实验室诊断病例发现率较低(每 85,000 名旅行者中一例)。[389]Dollard P, Griffin I, Berro A, et al. Risk assessment and management of COVID-19 among travelers arriving at designated U.S. airports, January 17-September 13, 2020. MMWR Morb Mortal Wkly Rep. 2020 Nov 13;69(45):1681-5.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6945a4.htm
http://www.ncbi.nlm.nih.gov/pubmed/33180758?tool=bestpractice.com
隔离:强制隔离主要针对有近期暴露潜在风险,易于区分的人群。尽管证据有限,但一项 Cochrane 评价发现隔离检疫对减少感染人数和死亡例数十分重要,尤其当较早开始启动,以及与其他防控措施结合使用时。但是,当前证据有限,因为大多数研究基于对于重要模型参数进行假设推拟的数学建模。[390]Nussbaumer-Streit B, Mayr V, Dobrescu AI, et al. Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review. Cochrane Database Syst Rev. 2020 Sep 14:CD013574.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013574.pub2/full
强制检疫可能带来长期的社会心理影响。[391]Mahase E. China coronavirus: what do we know so far? BMJ. 2020 Jan 24;368:m308.
https://www.bmj.com/content/368/bmj.m308/rr-2
http://www.ncbi.nlm.nih.gov/pubmed/31980434?tool=bestpractice.com
[392]Brooks SK, Webster RK, Smith LE, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020 Mar 14;395(10227):912-20.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30460-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32112714?tool=bestpractice.com
到达英国的旅行者须自我隔离 10 天,除非其来自豁免国家。若旅行者在到达前 10 天曾访问颁布旅行禁令国家,则从此类国家出发当天起算,需与其家庭成员共同进行自我隔离 10 天。
Public Health England: coronavirus (COVID-19) – how to self-isolate when you travel to the UK
external link opens in a new window
社交疏离
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。[393]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/
[394]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
将限制性非药物干预(例如强制居家和商企闭门令)强度更高的国家与限制性非药物干预强度更弱的国家相比,所有非药物干预的实施均将显著减少病例增长。但是,所有被研究国家中,相比强度更弱的限制性非药物干预,强度更高的限制性非药物干预未呈现清晰、显著的获益效应。应该指出的是,这项研究有重要的局限性。[395]Bendavid E, Oh C, Bhattacharya J, et al. Assessing mandatory stay-at-home and business closure effects on the spread of COVID-19. Eur J Clin Invest. 2021 Jan 5:e13484.
https://onlinelibrary.wiley.com/doi/10.1111/eci.13484
http://www.ncbi.nlm.nih.gov/pubmed/33400268?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。[396]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。[397]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。[398]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
屏蔽保护极端易感人群
屏蔽保护是一种用于保护易感人群(包括儿童)的措施,由于其基础疾病,他们极有可能遭受 COVID-19 重症侵袭。屏蔽保护包括最大程度减少极端易感者与他人之间的所有互动,以保护其免于接触病毒。
极端易感群体包括:[399]Public Health England. Guidance on shielding and protecting people who are clinically extremely vulnerable from COVID-19. 2021 [internet publication].
https://www.gov.uk/government/publications/guidance-on-shielding-and-protecting-extremely-vulnerable-persons-from-covid-19/guidance-on-shielding-and-protecting-extremely-vulnerable-persons-from-covid-19
实体器官移植受者
罹患特定肿瘤者
罹患严重呼吸道疾病(例如囊性纤维化、重度哮喘或重度 COPD)者
罹患罕见疾病,从而感染风险显著增加者(例如纯合子镰状细胞病、重症联合免疫缺陷)
接受免疫抑制治疗,足以增加感染风险者
伴脾脏疾患者(例如先前进行脾切除术)
伴唐氏综合征的成人
接受透析或伴慢性肾病的成人
罹患严重心脏疾患(先天性或获得性)女性
根据临床判断和对其需求的评估,亦被归类为临床极度脆弱者。
英国政府建议,根据当地公共卫生限制,应督促临床上极脆弱人群遵从特定的预防措施:
具体建议参考当前指南(各国建议可能有所不同)。
针对儿童和年轻成人的屏蔽保护建议已可获取。具体建议参考当前指南(各国建议可能有所不同)。
生活方式调整
生活方式改良(例如戒烟、减重)可有助于降低 COVID-19 风险,并且可能是其他干预措施的有用辅助手段。[400]Ho FK, Celis-Morales CA, Gray SR, et al. Modifiable and non-modifiable risk factors for COVID-19, and comparison to risk factors for influenza and pneumonia: results from a UK Biobank prospective cohort study. BMJ Open. 2020 Nov 19;10(11):e040402.
https://bmjopen.bmj.com/content/10/11/e040402.long
http://www.ncbi.nlm.nih.gov/pubmed/33444201?tool=bestpractice.com
WHO 建议,鉴于与烟草使用和二手烟暴露有关的公认危害,烟草使用者应停止使用烟草。[239]World Health Organization. Smoking and COVID-19: scientific brief. 2020 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Smoking-2020.2
英格兰公共卫生部亦建议停止吸烟。
Public Health England: COVID-19 – advice for smokers and vapers
external link opens in a new window
暴露前和暴露后预防
免疫护照
某些政府正在讨论或实施根据抗体检测结果对 COVID-19 感染和康复者进行认证(有时被称为“免疫护照”)。拥有该护照将使人们享有更多便利(例如工作、教育、旅行)。但是,WHO 并不支持此类认证,因为目前没有证据表明已从感染康复且具备抗体者将受到防止再感染的保护。[401]World Health Organization. "Immunity passports" in the context of COVID-19: scientific brief. 2020 [internet publication].
https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19
其他潜在问题包括公众对此类措施缺乏支持、潜在的群体歧视、检测错误(包括与其他人类冠状病毒出现交叉反应)、检测可及性、欺诈、法律和道德异议以及为获认证故意感染。[402]Kofler N, Baylis F. Ten reasons why immunity passports are a bad idea. Nature. 2020 May;581(7809):379-81.
https://www.nature.com/articles/d41586-020-01451-0
http://www.ncbi.nlm.nih.gov/pubmed/32439992?tool=bestpractice.com