Wee Liang En, Loy Enoch Xue Heng, Lim Jue Tao, Kwok Wei Hao, Chiew Calvin, Lien Christopher, Rosario Barbara Helen, Leong Ian Yi Onn, Merchant Reshma Aziz, Lye David Chien Boon, Tan Kelvin Bryan
National Centre for Infectious Diseases, Singapore 308442, Singapore.
Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore.
Vaccines (Basel). 2025 May 26;13(6):565. doi: 10.3390/vaccines13060565.
BACKGROUND/OBJECTIVES: Older adults with frailty are at-risk of worse outcomes following respiratory-viral-infections such as COVID-19. Data on effectiveness of vaccination/boosting in frail older adults during Omicron is lacking.
National healthcare-claims data and COVID-19 registries were utilized to enroll a cohort of older Singaporeans (≥60 years) as of 1 January 2022, divided into low/intermediate/high-risk for frailty; matching weights were utilized to adjust for sociodemographic differences/vaccination uptake at enrolment across frailty categories. Competing-risk-regression (Fine-Gray) taking death as a competing risk, with matching weights applied, was utilized to compare risks of COVID-19-related hospitalizations and severe COVID-19 across frailty levels (low/intermediate/high-risk), with estimates stratified by booster status. Individuals were followed up until study end-date (20 December 2023).
874,160 older adults were included during Omicron-predominant transmission; ~10% had intermediate/high-frailty-risk. Risk of hospitalization/severe COVID-19 was elevated in those with intermediate/high-frailty-risk up to XBB/JN.1 transmission. Boosting was associated with decreased risk of COVID-19-related hospitalization across all frailty categories in infection-naïve individuals. However, in infection-naïve older adults with high-frailty-risk, while receipt of first boosters was associated with lower risk of COVID-19-hospitalization/severe COVID-19, additional booster doses did not reduce risk. In reinfected older adults, first boosters were still associated with lower hospitalization risk (adjusted-hazards-ratio, aHR = 0.55, 95% CI = 0.33-0.92) among the non-frail, but not in the intermediate/high-frailty-risk minority.
First boosters were associated with reduced adverse COVID-19 outcomes across all frailty categories in infection-naïve older adults during Omicron. However, in the high-frailty minority, boosting did not additionally reduce risk in reinfected individuals with hybrid immunity, and beyond the first booster for infection-naïve individuals.
背景/目的：体弱的老年人在感染新冠病毒等呼吸道病毒后，出现更差预后的风险较高。目前缺乏关于奥密克戎毒株流行期间体弱老年人接种疫苗/加强针效果的数据。
利用国家医疗保健理赔数据和新冠病毒登记册，纳入截至2022年1月1日的一组新加坡老年人（≥60岁），分为体弱低/中/高风险组；使用匹配权重来调整不同体弱类别在入组时的社会人口统计学差异/疫苗接种率。采用以死亡为竞争风险的竞争风险回归（Fine-Gray法），并应用匹配权重，比较不同体弱水平（低/中/高风险）的新冠病毒相关住院风险和重症新冠病毒风险，估计值按加强针接种状态分层。对个体进行随访直至研究结束日期（2023年12月20日）。
在以奥密克戎毒株为主的传播期间，纳入了874,160名老年人；约10%有中/高体弱风险。在XBB/JN.1毒株传播之前，中/高体弱风险人群的住院/重症新冠病毒风险有所升高。在未感染过新冠病毒的个体中，加强针接种与所有体弱类别中新冠病毒相关住院风险降低有关。然而，在未感染过新冠病毒的高体弱风险老年人中，虽然接种第一剂加强针与降低新冠病毒住院/重症新冠病毒风险有关，但额外的加强针剂量并未降低风险。在再次感染的老年人中，第一剂加强针仍与非体弱人群较低的住院风险相关（调整后风险比，aHR = 0.55，95%置信区间 = 0.33 - 0.92），但在中/高体弱风险少数人群中并非如此。
在奥密克戎毒株流行期间，对于未感染过新冠病毒的老年人，第一剂加强针接种与所有体弱类别中不良新冠病毒结局风险降低有关。然而，在高体弱风险少数人群中，加强针接种并未进一步降低具有混合免疫的再次感染个体的风险，且对于未感染过新冠病毒的个体而言，超过第一剂加强针接种并无额外益处。
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