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. 2025 May 26;13(6):565.
doi: 10.3390/vaccines13060565.

Real-World Effectiveness of Boosting Against Omicron Hospitalization in Older Adults, Stratified by Frailty

Liang En Wee  1   2   3 , Enoch Xue Heng Loy  1 , Jue Tao Lim  4 , Wei Hao Kwok  1 , Calvin Chiew  1   5 , Christopher Lien  6 , Barbara Helen Rosario  6 , Ian Yi Onn Leong  4   7 , Reshma Aziz Merchant  8   9 , David Chien Boon Lye  1   4   9   10 , Kelvin Bryan Tan  1   2   4   5   9   11
Affiliations

Real-World Effectiveness of Boosting Against Omicron Hospitalization in Older Adults, Stratified by Frailty

Liang En Wee et al. Vaccines (Basel). .

Abstract

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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: Omicron; SARS-CoV-2; boosting; frailty; geriatrics; vaccination.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Cohort construction flowchart. Frailty risk was defined using the Hospital Frailty Risk Score (HFRS), stratified into the following categories: low (HFRS < 5), intermediate (HFRS 5–15), and high (HFRS > 15) risk of frailty.
Figure 2
Figure 2
Risk of Omicron COVID-19 related-hospitalization and severe disease in infection-naïve older adult Singaporeans, by number of booster doses/time since last vaccination, stratified by frailty. Frailty risk was defined using the Hospital Frailty Risk Score (HFRS), stratified into the following categories: low (HFRS < 5), intermediate (HFRS 5-15) and high (HFRS > 15) risk of frailty. Hazards-ratio (HR) estimated utilizing competing risks regression (Fine-Gray), controlling for age, gender, ethnicity, socioeconomic status (housing type), comorbidities, vaccination status as of point-of-infection (number of doses, time elapsed from last vaccination dose, type of vaccine [ancestral mRNA vaccine versus updated bivalent/XBB1.5 vaccine formulation). For number of vaccine doses, full vaccination (two-dose regimen) was taken as the reference category; for time-since-last-dose, >365 days since last dose was taken as the reference category. HR < 1 indicates lower risk of COVID-19 hospitalization/severe COVID-19; dots indicate HRs and error bars indicate the 95% confidence-intervals.
Figure 3
Figure 3
Risk of Omicron COVID-19 related-hospitalization in reinfected older adult Singaporeans, by number of booster doses/time since last vaccination, stratified by frailty.
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