背景:疫苗有效性(VE)研究巩固了在不同情况下对现实世界有效性的了解。然而,方法学问题可能会破坏他们的结论:评估意大利人群中针对COVID-19的VE,对有效性的特定威胁与绿色通行证政策的不同遵守情况的后果有关。
方法:为了应对这一挑战,我们在FriuliVeneziaGiulia地区(FVG)≥12岁的居民中进行了一项测试阴性病例对照(TNCC)研究和多重敏感性分析。意大利东北部,从2021年2月1日至2022年3月31日。从区域计算机化卫生数据库获得了有关211,437例COVID-19感染病例和845,748例匹配对照的信息。调查认为:COVID-19感染,住院治疗,和死亡。进行了多条件逻辑回归,对协变量进行了调整,VE估计为(1-ORCOVID-19接种疫苗与未接种疫苗)x100。进行了中介分析,以抵消潜在的对撞机变量,特别是,引入大流行限制后进行的拭子数量。
结果:抗感染的全周期VE从Alpha期的96%(95%CI:96,97)下降到Omicron期的43%(95%CI:42,45)。加强剂量将Omicron期的保护提高到67%(95%CI:66,67)。针对回避的Omicron变体,加强剂量对住院的保护率为87%(95%CI:83,90),对死亡的保护率为90%(95%CI:82,95).进行的拭子数量作为协变量包括在调整中,中介分析证实,它是疫苗接种和COVID-19相关结局之间的强中介.
结论:研究表明,在类似的TNCC设置下,应包括调解分析和诊断测试数量的调整,作为一种有效的方法来应对可能决定实质性选择偏差的差异测试行为的挑战。这种校正使我们能够与其他研究的结果保持一致,这些研究表明,针对感染的全周期VE最初是高的,但随着时间的推移,变异循环会降低。通过加强剂量平衡,提高对变体和结果严重程度的保护。
Vaccine effectiveness (VE) studies consolidate knowledge of real-world effectiveness in different contexts. However, methodological issues may undermine their conclusions: to assess the VE against COVID-19 within the Italian population, a specific threat to validity is related to the consequences of divergent compliance to the Green Pass policy.
To address this challenge we conducted a test negative
case-control (TNCC) study and multiple sensitivity analysis among residents aged ≥ 12 in Friuli Venezia Giulia Region (FVG), North-east Italy, from February 1, 2021 to March 31, 2022. Information regarding 211,437 cases of COVID-19 infection and 845,748 matched controls was obtained from the regional computerized health database. The investigation considered: COVID-19 infection, hospitalization, and death. Multiple conditional logistic regressions adjusted for covariates were performed and VE was estimated as (1-OR COVID-19vaccinated vs. unvaccinated)x100. Mediation analyses were carried out to offset potential collider variables, particularly, the number of swabs performed after the introduction of pandemic restrictions.
Full-cycle VE against infection decreased from 96% (95% CI: 96, 97) in the Alpha period to 43% (95% CI: 42, 45) in the Omicron period. Booster dose raised the protection in Omicron period to 67% (95% CI: 66, 67). Against the evasive Omicron variant, the protection of the booster dose was 87% (95% CI: 83, 90) for hospitalization and 90% (95% CI: 82, 95) for death. The number of swabs performed was included as a covariate in the adjustments, and the mediation analysis confirmed that it was a strong mediator between vaccination and COVID-19-related outcomes.
The study suggests that, under similar TNCC settings, mediation analysis and adjustment for number of diagnostic tests should be included, as an effective approach to the challenge of differential testing behavior that may determine substantial selection bias. This correction allowed us to align with results from other studies that show how full-cycle VE against infection was initially high but decreased over time by variant circulation, counterbalanced by booster dose that raised protection across variants and outcome severity.