COVID-19 vaccine effectiveness monitoring in Australia
Bette Liu A *A
Prof. Bette Liu is a medically trained epidemiologist and an associate director at the National Centre for Immunisation Research and Surveillance (NCIRS) in Australia. She leads the Population Health Group, which specialises in the use of large-scale linked data systems to provide evidence to support the introduction and evaluation of national vaccination programs. |
Abstract
Vaccine effectiveness is a measure of vaccine performance in the population usually estimated after the vaccine has been registered and is being used. With continuing evolution of SARS-CoV-2 and new variant-specific vaccines, as well as changes in uptake of vaccination and incidence of infections in the population, continued assessment of COVID-19 vaccine effectiveness is important to inform programmatic and policy decisions. In Australia, COVID-19 vaccine effectiveness against mortality has been assessed regularly using whole of population health data. These analyses have shown how vaccine boosting with the most up to date variant vaccines has been highly effective in reducing COVID-19 deaths in older adults. However, waning of protection continues to be observed supporting the need for regular boosters in older Australian adults and the need to continue to monitor the effectiveness of the COVID-19 vaccine program.
Keywords: cohort study, COVID-19, mortality, SARS-CoV-2, vaccine effectiveness.
In this fifth year of the COVID-19 pandemic we continue to see waves of infection and serious disease caused by SARS-CoV-2. However, with growing levels of vaccination including repeated booster doses and hybrid immunity, the number of hospital admissions and deaths related to COVID-19 has declined. The rolling 7-day average number of hospitalisations in Australia in June 2024 was 10-fold lower than the estimated numbers of hospitalisations in January 2022.1 COVID-19 continues to significantly affect healthcare with national surveillance systems reporting the 7-day rolling average number of cases in intensive care as ~80 in the most recent peak in June 2024.
COVID-19 vaccine effectiveness is a measure of the vaccine’s performance in the population usually estimated after a vaccine has been registered and is being used widely. It differs from vaccine efficacy, which is a measure of vaccine performance derived from clinical trials, usually conducted in the pre-registration phase.2 The primary aim of the sponsor initiated clinical trials of COVID-19 vaccine efficacy were focused on deriving data to support vaccine registration. Therefore, they often lacked sufficient statistical power to examine less common outcomes, such as hospitalisation or death, and did not have sufficient length of follow-up to estimate the duration of protection nor changes to efficacy as circulating viral variants evolved. Also, these trials were not designed to compare efficacy between different vaccine products such as vaccine brands or differences in antigen. These evidence gaps mean that studies of vaccine effectiveness and impact are needed to guide programmatic decision-making.
Summaries of studies on COVID-19 vaccine effectiveness are available online3 and in July 2024 there were an estimated 607 preprint and published reports from 52 countries. The vast majority of data has been generated on the mRNA vaccines produced by Pfizer BioNTech (Comirnaty) and Moderna (Spikevax) from Europe and the Americas. Relatively few reports have been generated from the World Health Organization (WHO) Western Pacific region, which includes Australia.
Focusing on reports of vaccine effectiveness during periods dominated by the SARS-CoV-2 Omicron variant, shows that both the primary course and booster vaccination from mRNA vaccines offer moderate protection against infection, with higher protection against measures of severe disease such as hospitalisation and death. Also, for both infection and severe disease, most studies demonstrate waning of protection by 6 months following dose receipt.
Evolution of the SARS-CoV-2 variant over time means that assessing vaccine effectiveness is an important component of vaccine program monitoring and surveillance. Significant reductions in vaccine effectiveness against the circulating variant, particularly against severe disease outcomes, signal that changes to the vaccine composition, booster schedule or other control measures may be required.
The WHO Technical Advisory Group on COVID-19 Vaccine Composition currently meets 6-monthly to make recommendations on methods to assess the impact of SARS-CoV-2 variants on vaccine performance, interpret data on variant impact on COVID-19 vaccines including vaccine effectiveness, and make recommendations on whether adaptations to the composition of COVID-19 vaccines are required.4 From 2022 the Group has made a number of recommendations on changes to COVID-19 vaccine composition, most recently in April 2024 when the use of a monovalent JN.1 lineage for the antigenic component of COVID-19 vaccines was recommended.5 Following the introduction of changes to the COVID-19 vaccine composition and roll-out to the population, assessment of vaccine effectiveness is important. This is to ensure that clinical and public health guidance on vaccine usage is evidence based.
Internationally, a number of groups conduct regular assessment of COVID-19 vaccine effectiveness and have provided information on both the bivalent ancestral and BA.1 or BA.4/5 COVID-19 vaccines and the monovalent XBB.1.5 vaccine. These data have proved useful for informing policy-making and clinical guidance on COVID-19 vaccine use internationally and in Australia.6–8 However, generating local vaccine effectiveness estimates remains important because the vaccine brands used and the recommended schedules and target groups in Australia may differ from other countries. Also there is the potential for the dominant circulating viral variants to differ by region.9
In Australia, a large national linked data collection, known as AIR-PLIDA (Australian Immunisation Register Person Level Integrated Data Asset; previously AIR-MADIP) has been used to assess COVID-19 vaccine effectiveness against COVID-19 mortality since 2022. The data collection is managed by the Australian Bureau of Statistics and includes a population-based linkage spine that enables data from a number of national collections to be linked for epidemiological analyses. Data that can be linked in order to conduct vaccine effectiveness analysis include the Australian Census, which was last conducted in 2021, COVID-19 immunisations from the Australian Immunisation Register (AIR) (reporting has been mandatory since February 2021), death registrations including the provisional cause of death, information on use of Medicare from the Medicare Benefits Schedule and dispensing of pharmaceutical items from the Pharmaceutical Benefits Scheme, as well as data on residence in aged care facilities. The AIR and death registrations are updated at least monthly enabling periodic assessment of vaccine effectiveness.
Using this data collection assessments of COVID-19 vaccine effectiveness against COVID-19 mortality in Australian adults aged 65 years and greater have been made during various waves of the pandemic.10 The analyses have shown that COVID-19 vaccines have been highly effective in preventing COVID-19 mortality. In early 2022 absolute estimates of vaccine effectiveness in preventing COVID-19 death were greater than 90% for a COVID-19 booster vaccine received within 3 months. In late 2022, with widespread transmission of SARS-CoV-2, and therefore growing hybrid immunity (immunity from both vaccination and natural infection), the estimates of the absolute vaccine effectiveness were lower but still more than 80%. This would be expected as many of those unvaccinated in early 2022 would have had SARS-CoV-2 infection and subsequently died of COVID-19. Also, these data show that vaccination was similarly effective among adults aged 65 years and older in aged care, as among those in this age group living in the community.
More recent analyses of these national data have demonstrated the substantial benefits of having a recent COVID-19 booster with variant-specific vaccine types including bivalent COVID-19 vaccines (ancestral and BA.1 or BA.4/5)11 and the monovalent COVID-19 XBB.1.5 vaccine.12 However, these analyses also show that COVID-19 vaccine effectiveness wanes with increasing time since vaccine receipt. This is consistent with international data.13 Therefore, regular boosting at 6-monthly intervals is needed for vulnerable people, principally the elderly in whom the benefit of a relative reduction in mortality is greatest.
Monitoring of vaccine effectiveness is a vital part of assessing new vaccine programs such as that for COVID-19. It ensures that use of vaccines and vaccine programs are based on the best available evidence and is particularly important as the SARS-CoV-2 pandemic continues to evolve.
Data availability
Data sharing is not applicable as no new data were generated or analysed during this study.
Declaration of funding
B. Liu’s institution receives research grants from the Australian National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF). This work did not receive any specific funding.
References
1 Australian Department of Health and Aged Care (2024) COVID-19 reporting. Commonwealth of Australia. https://www.health.gov.au/topics/covid-19/reporting#covid19-case-notifications (accessed 22 July 2024)
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Prof. Bette Liu is a medically trained epidemiologist and an associate director at the National Centre for Immunisation Research and Surveillance (NCIRS) in Australia. She leads the Population Health Group, which specialises in the use of large-scale linked data systems to provide evidence to support the introduction and evaluation of national vaccination programs. |