Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Department of Chemical Pathology, Chinese University of Hong Kong, Hong Kong, China.
BMJ. 2022 May 31;377:e069989. doi: 10.1136/bmj-2022-069989.
To evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital admission, and death.
Living systematic review and network meta-analysis.
World Health Organization covid-19 databases, including 38 sources of published studies and preprints.
Randomised controlled trials, cohort studies, and case-control studies.
38 WHO covid-19 databases were searched on a weekly basis from 8 March 2022 to 31 July 2022. Studies that assessed the effectiveness of heterologous and homologous covid-19 vaccine regimens with or without a booster were identified. Studies were eligible when they reported the number of documented, symptomatic, severe covid-19 infections, covid-19 related hospital admissions, or covid-19 related deaths among populations that were vaccinated and unvaccinated. The primary measure was vaccine effectiveness calculated as 1−odds ratio. Secondary measures were surface under the cumulative ranking curve (SUCRA) scores and the relative effects for pairwise comparisons. The risk of bias was evaluated by using the risk of bias in non-randomised studies of interventions (ROBINS-I) tool for all cohort and case-control studies. The Cochrane risk of bias tool (version 2; ROB-2) was used to assess randomised controlled trials.
The second iteration of the analysis comprised 63 studies. 25 combinations of covid-19 vaccine regimens were identified, of which three doses of mRNA vaccine were found to be 93% (95% credible interval 70% to 98%) effective against asymptomatic or symptomatic covid-19 infections for non-delta or non-omicron related infections. Heterologous boosting using two dose adenovirus vector vaccines with one dose mRNA vaccine showed a vaccine effectiveness of 94% (72% to 99%) against non-delta or non-omicron related asymptomatic or symptomatic infections. Three doses of mRNA vaccine were found to be the most effective in reducing non-delta or non-omicron related hospital admission (96%, 82% to 99%). The vaccine effectiveness against death in people who received three doses of mRNA vaccine remains uncertain owing to confounders. The estimate for a four dose mRNA vaccine regimen was of low certainty, as only one study on the effectiveness of four doses could be included in this update. More evidence on four dose regimens will be needed to accurately assess the effectiveness of a fourth vaccine dose. For people with delta or omicron related infection, a two dose regimen of an adenovirus vector vaccine with one dose of mRNA booster was 77% (42% to 91%) effective against asymptomatic or symptomatic covid-19 infections, and a three dose regimen of a mRNA vaccine was 93% (76% to 98%) effective against covid-19 related hospital admission.
An mRNA booster is recommended to supplement any primary vaccine course. Heterologous and homologous three dose regimens work comparably well in preventing covid-19 infections, even against different variants. The effectiveness of three dose vaccine regimens against covid-19 related death remains uncertain.
This review was not registered. The protocol is included in the supplementary document.
READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 31 May 2022 (BMJ 2022;377:e069989), and previous versions can be found as data supplements (https://www.bmj.com/content/377/bmj-2022-069989/related). When citing this paper please consider adding the version number and date of access for clarity.
评估异源和同源新冠疫苗方案（有无加强针）在预防新冠相关感染、住院和死亡方面的有效性。
实时系统评价和网络荟萃分析。
世界卫生组织新冠数据库，包括 38 个已发表研究和预印本来源。
随机对照试验、队列研究和病例对照研究。
从 2022 年 3 月 8 日至 2022 年 7 月 31 日，每周在世界卫生组织新冠数据库中进行搜索。确定评估异源和同源新冠疫苗方案（有无加强针）有效性的研究。当研究报告了疫苗接种和未接种人群中记录的、有症状的、严重的新冠感染、新冠相关住院或新冠相关死亡的数量时，研究即为合格。主要衡量指标为疫苗效力，计算方法为 1-比值比。次要衡量指标为累积排序曲线下面积（SUCRA）评分和两两比较的相对效果。使用非随机干预研究的偏倚风险（ROBINS-I）工具评估所有队列和病例对照研究的偏倚风险。使用随机对照试验的 Cochrane 偏倚风险工具（第 2 版；ROB-2）评估随机对照试验。
第二次分析迭代包括 63 项研究。确定了 25 种新冠疫苗方案组合，其中三剂 mRNA 疫苗对非德尔塔或非奥密克戎相关感染的无症状或有症状新冠感染的有效性为 93%（95%可信区间 70%至 98%）。使用两剂腺病毒载体疫苗加一剂 mRNA 疫苗进行异源加强针的疫苗效力为 94%（72%至 99%），可预防非德尔塔或非奥密克戎相关的无症状或有症状感染。三剂 mRNA 疫苗在降低非德尔塔或非奥密克戎相关住院方面最为有效（96%，82%至 99%）。由于混杂因素，mRNA 疫苗在预防死亡方面的有效性仍不确定。由于仅能纳入一项关于四剂疫苗有效性的研究，因此对四剂疫苗方案的估计确定性较低。需要更多关于四剂方案的证据，以准确评估第四剂疫苗的有效性。对于感染德尔塔或奥密克戎的人群，两剂腺病毒载体疫苗加一剂 mRNA 加强针对无症状或有症状新冠感染的有效性为 77%（42%至 91%），三剂 mRNA 疫苗对新冠相关住院的有效性为 93%（76%至 98%）。
建议使用 mRNA 加强针来补充任何初级疫苗接种方案。异源和同源三剂方案在预防新冠感染方面同样有效，即使是针对不同的变异株。三剂疫苗方案在预防新冠相关死亡方面的有效性仍不确定。
本综述未注册。方案包含在补充文件中。
本文是一篇实时系统评价，将根据新出现的证据进行更新。更新可能会在原始文章发表之日起长达两年内进行。这是原始文章于 2022 年 5 月 31 日（BMJ 2022；377：e069989）发表的更新 1 版本，以及之前的版本可以作为数据补充（https://www.bmj.com/content/377/bmj-2022-069989/related）。为了清晰起见，在引用本文时，请考虑添加版本号和访问日期。
