Relative effectiveness of COVID-19 vaccination with 3 compared to 2 doses against SARS-CoV-2 B.1.1.529 (Omicron) among an Australian population with low prior rates of SARS-CoV-2 infection

Abstract

Background: We estimate effectiveness of 3 versus 2 vaccine doses against SARS-CoV-2 B.1.1.529 Omicron in a mostly infection-naiive but highly vaccinated Australian population.

Methods: Cohort study of adults aged 40+ years resident in Sydney followed from 1 January 2022 for SARS-CoV-2 infection and COVID-19 hospitalisation or death using linked immunisation, disease notification and hospitalisation registers. Adjusted hazard ratios (aHR) and corresponding relative vaccine effectiveness (rVE) were estimated comparing 3 to 2 vaccine dose recipients by time since dose receipt, vaccine brand, and prior infection. Absolute risk reductions and numbers needed to boost by age groups were calculated.

Results: 2,053,123 infection-naiive individuals (mean age 59 years) were followed for 327,272 person-years for infection and 224,269 person-years for severe outcomes (hospitalisation/death). There were 175,849 infections and 4113 hospitalisations/deaths. Compared to individuals receiving dose 2 within the last 3 months, rVE in dose 3 recipients was 7% (95% CI 5-9%) against infection and 65% (95%CI 61-69%) against hospitalisation/death. Almost all dose 3 recipients had an mRNA vaccine; there was little difference in dose 3 rVE by primary course vaccine brand (ChAdOx1 versus BNT162b2). Over the 6-week follow-up, we estimated one hospitalisation/death was avoided for every 192 adults aged ≥70 years boosted with dose 3 in the infection-naiive cohort. The aHR for hospitalisation/death from Omicron was 0.12 (95 %CI 0.07-0.23) for 2-dose recipients with a prior Delta infection compared with 2-dose recipients with no prior infection.

Conclusions: Receipt of a third COVID-19 vaccine dose in adults aged 40 years and above significantly reduced hospitalisations and deaths from SARS-CoV-2 Omicron infections in a primarily infection-naiive population.

Fig. 1

Vaccine effectiveness relative to within 8–89 days of receipt of 2-doses of COVID-19 vaccine against SARS-CoV-2 Omicron infection and severe disease (hospitalisation/death). Squares represent the point estimate of vaccine effectiveness and their size is inversely proportional to the amount of data; lines represent the 95% confidence intervals with arrows indicating if the limit of the confidence interval goes beyond the scale shown. The reference category has no confidence interval. Relative VE estimate adjusted for age, sex, socioeconomic status, co-morbidity (see methods for definitions).

Fig. 2

Vaccine effectiveness relative to within 8–89 days of receipt of 2-doses of BNT162b2 Pfizer vaccine (reference) against SARS-CoV-2 Omicron severe disease (hospitalisation/death) by vaccine brand of primary course in 50–69 year olds. Squares represent the point estimate of vaccine effectiveness and their size is inversely proportional to the amount of data; lines represent the 95% confidence intervals with arrows indicating if the limit of the confidence interval goes beyond the scale shown. The reference category has no confidence interval. Relative VE estimate adjusted for age, sex, socioeconomic status, co-morbidity (see methods for definitions).

Fig. 3

Adjusted absolute rates of SARS-CoV-2 Omicron severe disease (hospitalisation/death) by age group and within the first 3 months of receipt of vaccine dose 2 or 3. Absolute rates adjusted for age, sex, socioeconomic status, co-morbidity (see methods for definitions).