Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study.
Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case-control study.
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与BNT162B2或Chadox1同源初级系列后的mRNA助推器对症状感染和巴西和苏格兰严重的Covid-19的有效性：一项测试阴性设计病例对照研究。
DOI：
10.1371/journal.pmed.1004156
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发表时间：
2023-01
期刊：
影响因子：
15.8
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自2021年9月以来，巴西和苏格兰已经在各自的人群中使用了mRNA助推器，Omicron的出现加速了他们的助推器计划。尽管如此，这两个国家最近报告的2019冠状病毒病（COVID-19）病例大幅增加。加强剂量对症状性Omicron病例和严重结局的保护作用持续时间尚不清楚。使用测试阴性设计，我们分析了国家数据库，以估计一个主要系列的疫苗有效性（VE），（与ChAdOx 1或BNT 162 b2）加mRNA疫苗加强剂（含BNT 162 b2或mRNA-1273）抗症状性严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染和严重的COVID-19结果（住院或死亡）在Omicron统治期间在巴西和苏格兰与未接种疫苗的个人相比。其他分析包括按年龄组（18 - 49岁，50 - 64岁，≥65岁）分层。所有在2022年1月1日至2022年4月23日期间在巴西和苏格兰报告急性呼吸道疾病症状并检测SARS-CoV-2感染的18岁或以上的人都有资格参加这项研究。在mRNA加强免疫后14至29天，ChAdOx 1加BNT 162 b2加强免疫对症状性SARS-CoV-2感染的VE在巴西为51.6%（95%置信区间（CI）：[51.0，52.2]，p < 0.001），在苏格兰为67.1%（95% CI [65.5，68.5]，p < 0.001）。在≥4个月时，对症状性感染的保护率在巴西下降至4.2%（95% CI [0.7，7.6]，p = 0.02），在苏格兰下降至37.4%（95% CI [33.8，40.9]，p < 0.001）。在巴西，针对严重结局的VE为93.5%（95% CI [93.0，94.0]，p < 0.001），在加强后14至29天，下降至82.3%（95% CI [79.7，84.7]，p < 0.001）和98.3%（95% CI [87.3，99.8]，p < 0.001）至77.8%（95% CI [51.4，89.9]，p < 0.001）。用BNT 162 b2加同源加强剂的初级系列获得了类似的结果。本研究的潜在局限性是，我们假设分析中纳入的所有病例均是由于Omicron变异所致，这是基于优势期和自加强剂量以来的有限随访时间。我们观察到，在使用mRNA或病毒载体疫苗的初级疫苗接种过程后，mRNA加强剂提供了针对Omicron症状性感染的适度、短暂的保护，但针对严重COVID-19结果的实质性和更持续的保护至少3个月。在一项测试阴性设计的病例对照研究中，Thiago Cerqueira-Silva博士及其同事研究了在巴西和苏格兰使用BNT 162 b2或ChAdOx 1进行同源初级系列后，mRNA增强剂对症状性感染和严重COVID-19的有效性。巴西和苏格兰一直在为接种两剂疫苗的人群提供助推器，以对抗导致2019年冠状病毒病（COVID-19）的冠状病毒。然而，在Omicron（一种SARS-CoV-2变种）出现后，这两个国家尽管加快了加强接种计划，但仍报告了大量COVID-19病例。关于加强剂量提供的保护持续时间的知识对于指导公共卫生建议至关重要。我们分析了2022年1月至4月期间来自巴西和苏格兰的国家数据库，以评估接受一系列病毒载体或mRNA抗COVID-19疫苗的个体中mRNA加强剂量提供的保护。对于接受病毒载体疫苗加mRNA加强免疫的个体，在加强免疫后14 - 29天至≥4个月，巴西的疫苗对症状性感染的有效性（VE）显著下降，从51.6%，95%置信区间（CI）：[51.0，52.2]降至4.2%。（95% CI：[0.7，7.6]，p = 0.02），苏格兰从67.1%（95% CI [65.5，68.5]，p < 0.001）至37.4%（95% CI [33.8，40.9]，p < 0.001）。在这些时期，在巴西观察到VE相对于严重结局略有下降，从93.5%（95% CI [93.0，94.0]，p < 0.001）至82.3%（95% CI [79.7，84.7]，p < 0.001），苏格兰从98.3%（95% CI [87.3，99.8]，p < 0.001）至77.8%（95% CI [51.4，89.9]，p < 0.001）。类似的结果，获得了一个同源加强后，一个主要系列的mRNA疫苗。在两个非常不同的国家中的类似发现使我们能够得出可靠的结果，因为有效性研究中存在潜在的偏倚来源，例如接种疫苗和未接种疫苗的个体之间的测试行为和未测量特征的差异，这些差异在两个国家中是无关的。在接种两剂载体病毒或mRNA疫苗加上一剂mRNA疫苗加强剂量后，观察到针对Omicron变体引起的症状感染的适度、短暂的保护作用。然而，至少在3个月内，对住院或死亡的保护是实质性的。
Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron’s emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear. Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, ≥65). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], p < 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p < 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p < 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p < 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p < 0.001) and 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose. We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months. In a test-negative design case-control study, Dr. Thiago Cerqueira-Silva and colleagues, investigate the effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland. Brazil and Scotland have been offering boosters for the population that received two doses of vaccines against the coronavirus that causes Coronavirus Disease 2019 (COVID-19). However, after Omicron (a SARS-CoV-2 variant) emerged, both countries reported a high number of COVID-19 cases despite accelerating their booster programs. Knowledge about the duration of the protection offered by the booster doses is essential to guide public health recommendations. We analyzed national databases from Brazil and Scotland between January and April 2022 to estimate the protection offered by mRNA booster doses in individuals who received a primary series of viral vector or mRNA anti-COVID-19 vaccines. For individuals that received primary series of viral vector vaccine plus mRNA booster, from 14 to 29 days to ≥4 months after the booster dose, vaccine effectiveness (VE) against symptomatic infection decreased significantly in Brazil from 51.6%, 95% confidence interval (CI): [51.0, 52.2], to 4.2% (95% CI: [0.7, 7.6], p = 0.02) and in Scotland from 67.1% (95% CI [65.5, 68.5], p < 0.001) to 37.4% (95% CI [33.8, 40.9], p < 0.001). In these periods, a slight decrease in VE was observed against severe outcomes in Brazil from 93.5% (95% CI [93.0, 94.0], p < 0.001) to 82.3% (95% CI [79.7, 84.7], p < 0.001) and in Scotland from 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 0.001). Similar results were obtained with a homologous booster after a primary series of mRNA vaccines. Similar findings in two very different countries allow us to draw reliable results because of potential sources of bias in effectiveness studies, such as differences in testing behavior and unmeasured characteristics between vaccinated and unvaccinated individuals, which are unrelated in the two countries. Modest, short-lived protection was observed against symptomatic infection caused by the Omicron variant after two doses of either vector viral or mRNA vaccine plus a booster dose with mRNA vaccine. However, protection against hospitalization or death was substantial for at least 3 months.