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

Liang En Wee; Enoch Xue Heng Loy; Jue Tao Lim; Wei Hao Kwok; Calvin Chiew; Christopher Lien; Barbara Helen Rosario; Ian Yi Onn Leong; Reshma Aziz Merchant; David Chien Boon Lye; Kelvin Bryan Tan

doi:10.3390/vaccines13060565

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

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

Authors

Liang En Wee^{1

2

3}, Enoch Xue Heng Loy¹, Jue Tao Lim⁴, Wei Hao Kwok¹, Calvin Chiew^{1

5}, Christopher Lien⁶, Barbara Helen Rosario⁶, 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

¹ National Centre for Infectious Diseases, Singapore 308442, Singapore.
² Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore.
³ Department of Infectious Diseases, Singapore General Hospital, Singapore 169608, Singapore.
⁴ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.
⁵ Ministry of Health, Singapore 169854, Singapore.
⁶ Department of Geriatric Medicine, Changi General Hospital, Singapore 529889, Singapore.
⁷ Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore 308433, Singapore.
⁸ Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore 119074, Singapore.
⁹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
¹⁰ Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore 308433, Singapore.
¹¹ Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.

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.