Waning of 2-Dose BNT162b2 and mRNA-1273 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Accounting for Depletion-of-Susceptibles Bias.

Waning of 2-Dose BNT162b2 and mRNA-1273 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Accounting for Depletion-of-Susceptibles Bias.
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DOI:
10.1093/aje/kwad017
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发表时间:
2023-06-02
影响因子:
5
通讯作者:
--
中科院分区:
医学2区
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在许可后评估中,对2019冠状病毒病(COVID-19)疫苗所赋予的保护期限产生了担忧。“易感者耗竭”是由接种疫苗和未接种疫苗个体之间感染累积差异驱动的偏倚,可能会模糊疫苗有效性(VE)估计值,妨碍解释。我们招募了加州居民,他们在一项匹配的、检测阴性设计的病例对照研究中接受了SARS-CoV-2分子检测,以估计2021年2月23日至12月5日期间基于mRNA的COVID-19疫苗的VE。我们使用条件Logistic回归模型分析了2次疫苗接种后保护作用的减弱。此外,我们使用了基于人群的血清学研究的数据,以调整“消耗的易感性”的偏见和估计VE的3个剂量,从第二次剂量接收的时间。BNT 162 b2和mRNA-1273对症状性SARS-CoV-2感染的合并VE在第二次给药后14天为91.3%(95%置信区间(CI):83.8,95.4),在7个月时下降至50.8%(95% CI:19.7,69.8)。调整易感性缺失偏倚后,我们估计初次mRNA疫苗接种系列后7个月的VE为53.2%(95%CI:23.6,71.2)。BN 162 b2或mRNA-1273的加强剂量使VE增加至95.0%(95%CI:82.8,98.6)。这些发现证实,观察到的保护作用减弱并不归因于流行病学偏倚,并支持为减轻COVID-19负担而给予额外疫苗剂量的持续努力。
Concerns about the duration of protection conferred by coronavirus disease 2019 (COVID-19) vaccines have arisen in postlicensure evaluations. “Depletion of susceptibles,” a bias driven by differential accrual of infection among vaccinated and unvaccinated individuals, may obscure vaccine effectiveness (VE) estimates, hindering interpretation. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design, case-control study to estimate VE of mRNA-based COVID-19 vaccines between February 23 and December 5, 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from a population-based serological study to adjust for “depletion-of-susceptibles” bias and estimated VE for 3 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval (CI): 83.8, 95.4) at 14 days after second-dose receipt and declined to 50.8% (95% CI: 19.7, 69.8) at 7 months. Adjusting for depletion-of-susceptibles bias, we estimated VE of 53.2% (95% CI: 23.6, 71.2) at 7 months after primary mRNA vaccination series. A booster dose of BN162b2 or mRNA-1273 increased VE to 95.0% (95% CI: 82.8, 98.6). These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19.
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