Objectives To estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant. Design Test negative design. Setting Long term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022. Participants After exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included. Main outcome measures Laboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously. Results 13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes. Conclusions The findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown. The dataset from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (eg, healthcare organisations and government) prohibit ICES from making the dataset publicly available, access may be granted to those who meet prespecified criteria for confidential access, available at (email: das@ices.on.ca). The full dataset creation plan and underlying analytical code are available from the authors on request, understanding that the computer programs might rely on coding templates or macros that are unique to ICES and are therefore either inaccessible or require modification.

中文翻译：

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第四剂 covid-19 mRNA 疫苗对加拿大安大略省长期护理居民中 omicron 变体的有效性：测试阴性设计研究


目的 评估第四剂与第三剂的边际有效性以及 mRNA covid-19 疫苗 BNT162b2 和 mRNA-1273 针对与 omicron 变体相关的任何感染、症状感染和严重后果（入院或死亡）的疫苗有效性。设计测试负片设计。设置加拿大安大略省长期护理机构，时间为 2021 年 12 月 30 日至 2022 年 4 月 27 日。 参与者 排除后，加拿大安大略省 626 个长期护理机构中 61 344 名 60 岁或以上的居民接受了 SARS-CoV-2 检测。包括。主要结果指标 实验室通过逆转录聚合酶链反应 (RT-PCR) 确认 omicron SARS-CoV-2 感染（任何和有症状），以及入院或死亡。使用多变量逻辑回归来估计边际有效性（四剂与三剂）和疫苗有效性（两剂、三剂或四剂与无剂），同时根据个人特征、合并症、测试周数和既往 SARS-CoV-2 阳性进行调整90 多天前的测试结果。结果 纳入了 13 654 名 omicron SARS-CoV-2 感染检测呈阳性的居民和 205 862 名检测呈阴性的对照居民。接种疫苗后 7 天或更长时间接种第四剂（95% 的疫苗接种者在第四剂中接受 mRNA-1273）与之前 84 天或更长时间接种第三剂的边际有效性为 19%（95% 置信区间 12% 至 26 %）对抗感染，31%（20%至41%）对抗有症状感染，40%（24%至52%）对抗严重后果。 疫苗接种者的疫苗有效性（与未接种疫苗的人相比）随着每增加一剂剂量而增加，第四剂疫苗对感染的有效性为 49%（95% 置信区间为 43% 至 54%），对有症状感染的有效性为 69%（61% 至 76%） ，86%（81% 至 90%）反对严重后果。结论 研究结果表明，与第三剂 mRNA covid-19 疫苗相比，第四剂可以改善长期护理居民在 omicron 主导时期对感染、症状感染和严重后果的保护。与未接种疫苗的居民相比，第四剂疫苗与接种疫苗的居民对严重后果的强烈保护相关，尽管保护的持续时间仍不清楚。本研究的数据集以编码形式安全地保存在 ICES 中。虽然 ICES 和数据提供商（例如医疗保健组织和政府）之间的合法数据共享协议禁止 ICES 公开提供数据集，但可以向符合预先指定的保密访问标准的人员授予访问权限，可通过（电子邮件：das@ices. on.ca）。作者可根据要求提供完整的数据集创建计划和基础分析代码，并了解计算机程序可能依赖于 ICES 特有的编码模板或宏，因此无法访问或需要修改。