Effectiveness of COVID-19 vaccine booster doses in adults aged 50 years and over during the Omicron period in Victoria, Australia

Background: Country-specific estimates of COVID-19 vaccine effectiveness (VE) are important for policy making, but analyses of COVID-19 VE in Australia have been limited to date. Methods: We used a modified Cox regression model to estimate the adjusted relative VE of three vs. two and four vs. three COVID-19 vaccine doses against hospitalisation and death due to COVID-19 among Victorians aged ≥50 years after the emergence of the Omicron SARS-CoV-2 variant through the linkage of national and state-wide health and administrative datasets. Analyses were conducted in two periods - 1 December 2021 to 19 June 2022 (Omicron BA.1/2 period; analyses of three vs. two doses), and 20 June 2022 to 7 November 2022 (Omicron BA.4/5 period; analyses of four vs. three doses). Results: Approximately 1.8 million people were included in analyses of three vs. two doses and approximately 1.2 million people were included in analyses of four vs. three doses. Adjusted relative VE against death soon after boosting with a third dose (compared to two doses) in individuals aged ≥65 years in the Omicron BA.1/2-dominant period reached 81.2% (95% confidence interval 76.9-84.6%). There was also evidence for a relative benefit of a third dose in the Omicron BA.1/2 period against hospitalisation and for a fourth dose in the Omicron BA.4/5 period against hospitalisation and death in this age group. In contrast, estimates of relative VE in the 50-64-year age group were highly imprecise. Conclusions: These results confirm the benefits of vaccine boosters in the Omicron era for those aged ≥65 years, with the most notable gains evident from a third dose in late 2021 to mid-2022.