Wee Liang En, Malek Muhammad Ismail Bin Abdul, Tan Janice, Chiew Calvin, Lee Vernon, Heng Derrick, Ong Benjamin, Lye David Chien, Tan Kelvin Bryan
National Centre for Infectious Diseases, Singapore; Duke-NUS Graduate Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore.
Ministry of Health, Singapore.
Vaccine. 2024 Dec 2;42(26):126356. doi: 10.1016/j.vaccine.2024.126356. Epub 2024 Sep 18.
Assessing population-wide risk-benefit ratio of COVID-19 vaccination remains relevant in the current era of Omicron endemicity and boosting. Assessments of mortality risk and cardiovascular events post-vaccination/infection were generally made prior to emergence of milder Omicron and booster rollout.
Retrospective cohort study from 6th January to 31st December 2022 (Omicron-predominant transmission), amongst adult Singaporeans aged ≥18 years. Cox regression models adjusted for demographics/comorbidities were used to estimate risk of all-cause mortality and cardiovascular events 0-180 days post-mRNA vaccination/SARS-CoV-2 infection, compared to >180 days post-mRNA vaccination. Risk periods post-vaccination were further stratified by presence/absence of SARS-CoV-2 infection in the preceding 180 days; similarly, risk periods post-infection were further stratified by vaccination in the 180 days preceding infection.
3,137,210 adults participated, with 2,047,008 vaccine doses administered (99 % being booster doses) and 1,189,846 infections. 23,028 deaths and 54,017 cardiac events were recorded. No elevated risk of all-cause mortality/cardiovascular events was observed across all age strata post-vaccination. Conversely, all-cause mortality post-infection remained elevated up to >180 days in older adults (≥60 years), compared to person-time > 180 days post-vaccination. For vaccine-breakthrough SARS-CoV-2 infection in older adults vaccinated <180 days prior, risk of mortality was only elevated up to 60 days post-infection, but not beyond. Elevated risk of cardiovascular events 1-2 months after any SARS-CoV-2 infection was observed across all age strata, with elevated risk observed in older adults >180 days post-infection (adjusted-hazards-ratio, aHR = 1.18, 95 %CI = 1.04-1.34). Preceding vaccination within 180 days prior to infection attenuated this risk, with no significantly elevated post-acute risk of cardiovascular events (>180 days: aHR = 1.10, 95 %CI = 0.95-1.07).
No increased risk of all-cause mortality or cardiovascular events was observed up to 180 days after any mRNA vaccination dose in the Omicron era; vaccination attenuated post-acute cardiovascular risk in older adults. The risk-benefit ratio of vaccination remained positive during Omicron.
在当前奥密克戎流行和加强接种的时代，评估新冠疫苗接种在全人群中的风险效益比仍然具有现实意义。对疫苗接种/感染后死亡率风险和心血管事件的评估通常是在症状较轻的奥密克戎毒株出现和加强接种推广之前进行的。
对2022年1月6日至12月31日（以奥密克戎为主导传播）期间年龄≥18岁的成年新加坡人进行回顾性队列研究。使用针对人口统计学/合并症进行调整的Cox回归模型，估计mRNA疫苗接种/SARS-CoV-2感染后0至180天与mRNA疫苗接种后>180天相比的全因死亡率和心血管事件风险。接种疫苗后的风险期根据前180天内是否存在SARS-CoV-2感染进一步分层；同样，感染后的风险期根据感染前180天内是否接种疫苗进一步分层。
3,137,210名成年人参与研究，共接种2,047,008剂疫苗（99%为加强针），发生1,189,846次感染。记录到23,028例死亡和54,017例心脏事件。接种疫苗后，所有年龄组均未观察到全因死亡率/心血管事件风险升高。相反，与接种疫苗后>180天的人时相比，老年人（≥60岁）感染后的全因死亡率在>180天内仍保持升高。对于接种疫苗<180天前的老年人发生的疫苗突破性SARS-CoV-2感染，死亡风险仅在感染后60天内升高，但之后未升高。在所有年龄组中，任何SARS-CoV-2感染后1至2个月心血管事件风险升高，在感染后>180天的老年人中观察到风险升高（调整后风险比，aHR = 1.18，95%CI = 1.04 - 1.34）。感染前180天内接种疫苗可减轻这种风险，急性后期心血管事件风险无显著升高（>180天：aHR = 1.10，95%CI = 0.95 - 1.07）。
在奥密克戎时代，任何mRNA疫苗接种剂量后180天内未观察到全因死亡率或心血管事件风险增加；接种疫苗可减轻老年人急性后期心血管风险。在奥密克戎期间，疫苗接种的风险效益比仍然是积极的。
