Table_12_Meta-analysis of hybrid immunity to mitigate the risk of Omicron variant reinfection.DOCX

BackgroundHybrid immunity (a combination of natural and vaccine-induced immunity) provides additional immune protection against the coronavirus disease 2019 (COVID-19) reinfection. Today, people are commonly infected and vaccinated; hence, hybrid immunity is the norm. However, the mitigation of the risk of Omicron variant reinfection by hybrid immunity and the durability of its protection remain uncertain. This meta-analysis aims to explore hybrid immunity to mitigate the risk of Omicron variant reinfection and its protective durability to provide a new evidence-based basis for the development and optimization of immunization strategies and improve the public’s awareness and participation in COVID-19 vaccination, especially in vulnerable and at-risk populations.MethodsEmbase, PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for publicly available literature up to 10 June 2024. Two researchers independently completed the data extraction and risk of bias assessment and cross-checked each other. The Newcastle-Ottawa Scale assessed the risk of bias in included cohort and case–control studies, while criteria recommended by the Agency for Health Care Research and Quality (AHRQ) evaluated cross-sectional studies. The extracted data were synthesized in an Excel spreadsheet according to the predefined items to be collected. The outcome was Omicron variant reinfection, reported as an Odds Ratio (OR) with its 95% confidence interval (CI) and Protective Effectiveness (PE) with 95% CI. The data were pooled using a random- or fixed-effects model based on the I2 test. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.ResultsThirty-three articles were included. Compared with the natural immunity group, the hybrid immunity (booster vaccination) group had the highest level of mitigation in the risk of reinfection (OR = 0.43, 95% CI:0.34–0.56), followed by the complete vaccination group (OR = 0.58, 95% CI:0.45–0.74), and lastly the incomplete vaccination group (OR = 0.64, 95% CI:0.44–0.93). Compared with the complete vaccination-only group, the hybrid immunity (complete vaccination) group mitigated the risk of reinfection by 65% (OR = 0.35, 95% CI:0.27–0.46), and the hybrid immunity (booster vaccination) group mitigated the risk of reinfection by an additional 29% (OR = 0.71, 95% CI:0.61–0.84) compared with the hybrid immunity (complete vaccination) group. The effectiveness of hybrid immunity (incomplete vaccination) in mitigating the risk of reinfection was 37.88% (95% CI, 28.88–46.89%) within 270–364 days, and decreased to 33.23%% (95% CI, 23.80–42.66%) within 365–639 days; whereas, the effectiveness after complete vaccination was 54.36% (95% CI, 50.82–57.90%) within 270–364 days, and the effectiveness of booster vaccination was 73.49% (95% CI, 68.95–78.04%) within 90–119 days.ConclusionHybrid immunity was significantly more protective than natural or vaccination-induced immunity, and booster doses were associated with enhanced protection against Omicron. Although its protective effects waned over time, vaccination remains a crucial measure for controlling COVID-19.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier, CRD42024539682.

背景：混合免疫（自然免疫与疫苗接种诱导免疫的结合）为抵抗2019冠状病毒病（COVID-19）的再次感染提供了额外的免疫保护。当前，人们普遍感染并接种疫苗；因此，混合免疫已成为常态。然而，混合免疫在降低奥密克戎变异株再次感染风险方面的作用及其保护效果的持久性仍存在不确定性。本研究旨在探讨混合免疫对降低奥密克戎变异株再次感染风险及其保护效果的持久性，以提供新的基于证据的依据，为免疫策略的开发与优化提供参考，并提高公众对COVID-19疫苗接种的认识和参与度，尤其是在易感和高风险人群中。方法：检索了截至2024年6月10日公开发表的文献，包括Embase、PubMed、Web of Science、中国知网和万方数据库。两位研究人员独立完成了数据提取和偏倚风险评估，并相互核查。采用Newcastle-Ottawa量表评估纳入队列研究和病例对照研究的偏倚风险，而美国卫生保健研究与质量局（AHRQ）推荐的标准则用于评估横断面研究。提取的数据根据预定义的收集项目汇总在Excel表格中。结果以Omicron变异株再次感染为结果指标，报告其比值比（OR）及其95%置信区间（CI）和保护效果（PE）及其95%置信区间。根据I2测试结果，使用随机效应模型或固定效应模型对数据进行汇总。遵循系统评价和Meta分析报告规范（PRISMA）指南。结果：共纳入33篇文章。与自然免疫组相比，混合免疫（加强疫苗接种）组在降低再次感染风险方面具有最高水平（OR = 0.43，95% CI: 0.34–0.56），其次是完整疫苗接种组（OR = 0.58，95% CI: 0.45–0.74），最后是不完整疫苗接种组（OR = 0.64，95% CI: 0.44–0.93）。与仅完整疫苗接种组相比，混合免疫（完整疫苗接种）组降低了65%的再次感染风险（OR = 0.35，95% CI: 0.27–0.46），而与混合免疫（完整疫苗接种）组相比，混合免疫（加强疫苗接种）组进一步降低了29%的再次感染风险（OR = 0.71，95% CI: 0.61–0.84）。在270–364天内，混合免疫（不完整疫苗接种）在降低再次感染风险方面的有效性为37.88%（95% CI，28.88–46.89%），并在365–639天内降至33.23%%（95% CI，23.80–42.66%）；而完整疫苗接种后的有效性为54.36%（95% CI，50.82–57.90%），加强疫苗接种的有效性在90–119天内为73.49%（95% CI，68.95–78.04%）。结论：混合免疫相较于自然或疫苗接种诱导的免疫具有显著的防护作用，加强剂量的应用与增强对奥密克戎的保护相关。尽管其保护效果随时间减弱，但疫苗接种依然是控制COVID-19的关键措施。系统评价注册：https://www.crd.york.ac.uk/PROSPERO/，标识符：CRD42024539682。