Objective 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. Design Living systematic review and network meta-analysis. Data sources World Health Organization covid-19 databases, including 38 sources of published studies and preprints. Study selection Randomised controlled trials, cohort studies, and case-control studies. Methods 38 WHO covid-19 databases were searched on a weekly basis from 8 March 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. Results The first round of the analysis comprised 53 studies. 24 combinations of covid-19 vaccine regimens were identified, of which a three dose mRNA regimen was found to be the most effective against asymptomatic and symptomatic covid-19 infections (vaccine effectiveness 96%, 95% credible interval 72% to 99%). Heterologous boosting using two dose adenovirus vector vaccines with one mRNA vaccine has a satisfactory vaccine effectiveness of 88% (59% to 97%). A homologous two dose mRNA regimen has a vaccine effectiveness of 99% (79% to 100%) in the prevention of severe covid-19 infections. Three dose mRNA is the most effective in reducing covid-19 related hospital admission (95%, 90% to 97%). The vaccine effectiveness against death in people who received three doses of mRNA vaccine remains uncertain owing to confounders. In the subgroup analyses, a three dose regimen is similarly effective in all age groups, even in the older population (≥65 years). A three dose mRNA regimen works comparably well in patients who are immunocompromised and those who are non-immunocompromised. Homologous and heterologous three dose regimens are effective in preventing infection by covid-19 variants (alpha, delta, and omicron). Conclusion 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. Systematic review registration 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. Raw data in this systematic review with meta-analysis are extracted from published and preprint studies available on the internet. Our processed data for network meta-analysis and R codes on GitHub ().

中文翻译：

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异源和同源 covid-19 疫苗方案的有效性：通过网络荟萃分析进行实时系统评价

目的 评估有或没有加强的异源和同源 covid-19 疫苗方案在预防 covid-19 相关感染、住院和死亡方面的有效性。设计生活系统回顾和网络荟萃分析。数据来源世界卫生组织 covid-19 数据库，包括 38 个已发表研究和预印本的来源。研究选择 随机对照试验、队列研究和病例对照研究。方法 自 2022 年 3 月 8 日起，每周检索 38 个 WHO covid-19 数据库。确定了评估有或没有加强剂的异源和同源 covid-19 疫苗方案有效性的研究。当研究报告了已接种疫苗和未接种疫苗的人群中记录的、有症状的严重 covid-19 感染、与 covid-19 相关的住院人数或与 covid-19 相关的死亡人数时，研究就符合资格。主要衡量标准是按 1−优势比计算的疫苗有效性。次要指标是累积排名曲线（SUCRA）分数下的表面和成对比较的相对效应。通过对所有队列和病例对照研究使用非随机干预研究偏倚风险 (ROBINS-I) 工具来评估偏倚风险。Cochrane 偏倚风险工具（第 2 版；ROB-2）用于评估随机对照试验。结果 第一轮分析包含 53 项研究。确定了 24 种 covid-19 疫苗方案组合，其中发现三剂 mRNA 方案对无症状和有症状的 covid-19 感染最有效（疫苗有效性 96%，95% 可信区间 72% 至 99%）。使用两剂腺病毒载体疫苗和一种 mRNA 疫苗进行异源加强，疫苗效果令人满意，达到 88%（59% 至 97%）。同源两剂 mRNA 方案在预防严重 covid-19 感染方面的疫苗有效性为 99%（79% 至 100%）。三剂 mRNA 对于减少与 covid-19 相关的入院率最有效（95%、90% 至 97%）。由于混杂因素，接受三剂 mRNA 疫苗的疫苗对死亡的有效性仍不确定。在亚组分析中，三剂量方案在所有年龄组中都同样有效，甚至在老年人群（≥65 岁）中也是如此。三剂量 mRNA 方案对于免疫功能低下和非免疫功能低下的患者效果相当好。同源和异源三剂量方案可有效预防 covid-19 变体（α、δ 和 omicron）感染。结论 建议使用 mRNA 加强疫苗来补充任何初级疫苗疗程。异源和同源三剂量方案在预防 covid-19 感染方面效果相当好，甚至针对不同的变种也是如此。三剂疫苗方案针对 covid-19 相关死亡的有效性仍不确定。系统评论注册 该评论未注册。该协议包含在补充文件中。读者须知本文是一篇动态系统综述，将进行更新以反映新出现的证据。自原始发布之日起两年内可能会进行更新。本系统综述和荟萃分析中的原始数据摘自互联网上已发表和预印本的研究。我们在 GitHub 上处理的网络元分析数据和 R 代码（）。