Ministry of Health, Santiago, Chile; Facultad de Matemáticas, Pontificia Universidad Católica de Chile, Santiago, Chile; Millennium Nucleus Center for the Discovery of Structures in Complex Data, Santiago, Chile.
Escuela de Gobierno, Pontificia Universidad Católica de Chile, Santiago, Chile; Millennium Initiative for Collaborative Research in Bacterial Resistance, Santiago, Chile; Research Center for Integrated Disaster Risk Management, Santiago, Chile; CIFAR Azrieli Global Scholars Program, CIFAR, Toronto, ON, Canada.
Lancet Glob Health. 2022 Jun;10(6):e798-e806. doi: 10.1016/S2214-109X(22)00112-7. Epub 2022 Apr 23.
BACKGROUND: Several countries have authorised or begun using a booster vaccine dose against COVID-19. Policy makers urgently need evidence of the effectiveness of additional vaccine doses and its clinical spectrum for individuals with complete primary immunisation schedules, particularly in countries where the primary schedule used inactivated SARS-CoV-2 vaccines. METHODS: Using individual-level data, we evaluated a prospective, observational, national-level cohort of individuals (aged ≥16 years) affiliated with the Fondo Nacional de Salud insurance programme in Chile, to assess the effectiveness of CoronaVac (Sinovac Biotech), AZD1222 (Oxford-AstraZeneca), or BNT162b2 (Pfizer-BioNTech) vaccine boosters in individuals who had completed a primary immunisation schedule with CoronaVac, compared with unvaccinated individuals. Individuals administered vaccines from Feb 2, 2021, to the prespecified study end date of Nov 10, 2021, were evaluated; we excluded individuals with a probable or confirmed SARS-CoV-2 infection (RT-PCR or antigen test) on or before Feb 2, 2021, and individuals who had received at least one dose of any COVID-19 vaccine before Feb 2, 2021. We estimated the vaccine effectiveness of booster doses against laboratory-confirmed symptomatic COVID-19 (symptomatic COVID-19) cases and COVID-19 outcomes (hospitalisation, admission to the intensive care unit [ICU], and death We used inverse probability-weighted and stratified survival regression models to estimate hazard ratios, accounting for time-varying vaccination status and adjusting for relevant demographic, socioeconomic, and clinical confounders. We estimated the change in hazard from unvaccinated status to vaccinated status associated with the primary immunisation series and a booster vaccine. FINDINGS: 11 174 257 individuals were eligible for this study, among whom 4 127 546 completed a primary immunisation schedule (two doses) with CoronaVac and received a booster dose during the study period. 1 921 340 (46·5%) participants received an AZD1222 booster, 2 019 260 (48·9%) received a BNT162b2 booster, and 186 946 (4·5%) received a homologous booster with CoronaVac. We calculated an adjusted vaccine effectiveness (weighted stratified Cox model) in preventing symptomatic COVID-19 of 78·8% (95% CI 76·8-80·6) for a three-dose schedule with CoronaVac, 96·5% (96·2-96·7) for a BNT162b2 booster, and 93·2% (92·9-93·6) for an AZD1222 booster. The adjusted vaccine effectiveness against COVID-19-related hospitalisation, ICU admission, and death was 86·3% (83·7-88·5), 92·2% (88·7-94·6), and 86·7% (80·5-91·0) for a homologous CoronaVac booster, 96·1% (95·3-96·9), 96·2% (94·6-97·3), and 96·8% (93·9-98·3) for a BNT162b2 booster, and 97·7% (97·3-98·0), 98·9% (98·5-99·2), and 98·1% (97·3-98·6) for an AZD1222 booster. INTERPRETATION: Our results suggest that a homologous or heterologous booster dose for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against COVID-19, including severe disease and death. Heterologous boosters showed higher vaccine effectiveness than a homologous booster for all outcomes, providing additional support for a mix-and-match approach. FUNDING: Agencia Nacional de Investigación y Desarrollo through the Fondo Nacional de Desarrollo Científico y Tecnológico, Millennium Science Initiative Program, and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias.
背景: 一些国家已经授权或开始使用 COVID-19 加强疫苗剂量。政策制定者迫切需要针对完全初级免疫接种方案的个体的额外疫苗剂量及其临床范围的证据,特别是在使用灭活 SARS-CoV-2 疫苗的初级方案的国家。
方法: 使用个体水平数据,我们评估了智利国家卫生基金保险计划(Fondo Nacional de Salud)中年龄≥16 岁的个体的前瞻性、观察性、国家级队列,以评估 CoronaVac(科兴)、AZD1222(牛津-阿斯利康)或 BNT162b2(辉瑞-生物科技)疫苗加强剂在已完成 CoronaVac 初级免疫接种方案的个体中的有效性,与未接种个体相比。评估了 2021 年 2 月 2 日至 2021 年 11 月 10 日规定的研究结束日期之间接种疫苗的个体;我们排除了在 2021 年 2 月 2 日之前或之前的任何一天有 SARS-CoV-2 感染(RT-PCR 或抗原检测)的个体,以及在 2021 年 2 月 2 日之前至少接种过一剂任何 COVID-19 疫苗的个体。我们估计了针对实验室确诊的有症状 COVID-19(有症状 COVID-19)病例和 COVID-19 结果(住院、入住重症监护病房[ICU]和死亡)的加强剂量的疫苗有效性。我们使用逆概率加权和分层生存回归模型估计风险比,考虑时间变化的疫苗接种状态,并调整相关的人口统计学、社会经济和临床混杂因素。我们估计了与初级免疫系列和加强疫苗接种相关的从未接种状态到接种状态的风险变化。
结果: 1174257 名个体符合本研究条件,其中 4127546 名个体完成了 CoronaVac 的初级免疫接种方案(两剂),并在研究期间接受了加强剂量。1921340 名(46.5%)参与者接受了 AZD1222 加强剂,2019260 名(48.9%)接受了 BNT162b2 加强剂,186946 名(4.5%)接受了同源 CoronaVac 加强剂。我们计算了 CoronaVac 三剂方案预防有症状 COVID-19 的调整后的疫苗有效性(加权分层 Cox 模型)为 78.8%(95%CI 76.8-80.6),BNT162b2 加强剂为 96.5%(96.2-96.7),AZD1222 加强剂为 93.2%(92.9-93.6)。与 COVID-19 相关的住院、ICU 入院和死亡的调整后疫苗有效性为同源 CoronaVac 加强剂的 86.3%(83.7-88.5)、92.2%(88.7-94.6)和 86.7%(80.5-91.0),BNT162b2 加强剂为 96.1%(95.3-96.9)、96.2%(94.6-97.3)和 96.8%(93.9-98.3),AZD1222 加强剂为 97.7%(97.3-98.0)、98.9%(98.5-99.2)和 98.1%(97.3-98.6)。
解释: 我们的结果表明,对于已完成 CoronaVac 初级免疫接种方案的个体,同源或异源加强剂量可提供针对 COVID-19 的高水平保护,包括严重疾病和死亡。异源加强剂在所有结果中的疫苗有效性均高于同源加强剂,为混合和匹配方法提供了额外支持。
资助: 国家研究与发展机构通过国家科学技术发展基金、千年科学倡议计划和优先领域研究中心资助基金提供资金。
Front Immunol. 2025-5-9
J Nanobiotechnology. 2025-2-18
J Nanobiotechnology. 2025-2-8
Open Forum Infect Dis. 2024-9-10
Ther Adv Vaccines Immunother. 2024-9-27
N Engl J Med. 2021-12-23
N Engl J Med. 2021-12-9