Tsang Tim K, Sullivan Sheena G, Huang Xiaotong, Wang Can, Peng Liping, Yang Bingyi, Cowling Benjamin J
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
School of Clinical Sciences, Monash University, Melbourne, Australia.
medRxiv. 2025 May 8:2025.05.08.25327221. doi: 10.1101/2025.05.08.25327221.
The intensity and duration of exposure can influence vaccine effectiveness (VE). For "leaky" vaccines such as SARS-CoV-2 vaccines, which reduce but do not entirely prevent infections, repeated or prolonged exposures may increase breakthrough infection likelihood. To test this hypothesis, we conducted a systematic review and meta-analysis of 76 test-negative design studies reporting VE against SARS-CoV-2 infection or severe disease. Exposure intensity was approximated using Oxford COVID-19 Government Response Tracker indices: Stringency Index (SI), Containment and Health Index (CHI), and Government Response Index (GRI). Based on 1,419 VE estimates, pooled VE against infection was significantly higher in settings with higher index values (lower exposure intensity): 82% (95% CI: 80-83%) in high-SI settings versus 39% (95% CI: 35-43%) in low-SI settings. Similar patterns appeared for other indices and severe disease outcomes. These associations persisted in meta-regression models adjusting for viral variant, vaccine type, time since vaccination, prior infection status, and enrollment criteria. Correlation analyses showed moderate-to-strong positive correlations between VE estimates and exposure indices (Spearman's correlation: 0.50-0.62). These findings establish exposure intensity as a critical effect modifier of SARS-CoV-2 VE, demonstrating the leaky nature of COVID-19 vaccines and explaining heterogeneity in real-world effectiveness estimates. Future VE evaluations and vaccination strategies should account for exposure intensity to ensure accurate, context-specific estimates.
暴露的强度和持续时间会影响疫苗效力(VE)。对于像SARS-CoV-2疫苗这样的“有漏洞”疫苗,即能减少但不能完全预防感染的疫苗,反复或长时间暴露可能会增加突破性感染的可能性。为了验证这一假设,我们对76项报告针对SARS-CoV-2感染或重症的疫苗效力的检测阴性设计研究进行了系统评价和荟萃分析。使用牛津大学COVID-19政府应对追踪指数来估算暴露强度:严格指数(SI)、遏制与健康指数(CHI)以及政府应对指数(GRI)。基于1419项疫苗效力估计值,在指数值较高(暴露强度较低)的环境中,针对感染的合并疫苗效力显著更高:高SI环境中为82%(95%置信区间:80 - 83%),而低SI环境中为39%(95%置信区间:35 - 43%)。其他指数和重症结果也呈现出类似模式。在针对病毒变异株、疫苗类型、接种后时间、既往感染状况和纳入标准进行调整的荟萃回归模型中,这些关联依然存在。相关性分析显示疫苗效力估计值与暴露指数之间存在中度至强的正相关(斯皮尔曼相关性:0.50 - 0.62)。这些发现确立了暴露强度是SARS-CoV-2疫苗效力的关键效应修饰因素,证明了COVID-19疫苗的有漏洞性质,并解释了实际效力估计中的异质性。未来的疫苗效力评估和疫苗接种策略应考虑暴露强度,以确保准确的、针对具体情况的估计。
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