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.