ATAGI notes that the course of the COVID-19 pandemic has significantly changed in recent weeks. Case numbers of COVID-19 due to the Omicron variant are rapidly increasing and this variant now dominates in some regions of Australia. Internationally, the Omicron variant has become dominant in several countries with case numbers growing rapidly in some. Preliminary data from large superspreading events in New South Wales involving younger people suggested that two doses of vaccine did not provide any significant protection against SARS-CoV-2 infection due to the Omicron variant.
Strong evidence has accumulated over the past two weeks to indicate that booster doses of COVID-19 vaccines are likely to increase protection against infection with the Omicron variant. Although some early data suggest that the risk of hospitalisation due to disease caused by the Omicron variant is lower than that with the Delta variant, this difference would not be enough to offset the impact of high case numbers on the health system.
There are now reassuring data on the safety of early booster doses in tens of millions of people, with no new safety signals identified in the United Kingdom where more than 21 million booster doses have been delivered.
ATAGI expects that booster vaccination alone will not be sufficient to avert a surge due to Omicron. However, maximising booster coverage by expanding eligibility and encouraging high uptake, in combination with enhanced public health and social measures, may prevent a large surge in case numbers, hospitalisations and deaths. ATAGI also acknowledges the demands that the booster and paediatric COVID-19 vaccination programs will have on the immunisation workforce.
- In light of emerging evidence, ATAGI now recommends that the eligibility for COVID-19 booster vaccination be expanded for adults aged 18 and older.
- ATAGI recommends bringing forward the minimum interval between the primary course and the booster dose from 5 months to 4 months as soon as practical, noting the holiday period. It is understood that this is achievable from 4 January, although some providers may have flexibility to administer before that time.
- As soon as practical, ATAGI recommends providing boosters to all eligible adults from a minimum of 3 months following the second dose of the primary course.
- Pregnant women aged 18 or older who received their primary COVID-19 vaccination course ≥ 4 months ago are recommended to have a booster dose. When practical and in line with the broader community, this interval should be brought forward to 3 months.
- Immunocompromised individuals who have received 3 primary doses of a COVID-19 vaccine are also recommended to have a booster dose in line with the timing for the general population, i.e., currently a 4-month interval from their primary course, and when capacity permits, 3 months.
- ATAGI reinforces that timely receipt of a booster dose is particularly important for:
- people with risk factors for severe disease (including those aged ≥60 years, those with underlying medical conditions, those in aged/disability care and Aboriginal and Torres Strait Islander peoples); and
- people with increased risk of exposure to SARS-CoV-2. This may include those in an outbreak area, or those with a high risk of occupational exposure. The impact of occupational risks is magnified in settings where workers may transmit the virus to others with increased risk of severe disease, such as aged/disability care facilities.
- ATAGI recommends that providers and jurisdictional immunisation program coordinators encourage and facilitate access for those at greatest risk to receive COVID-19 boosters as a priority.
- Both Comirnaty (Pfizer) or Spikevax (Moderna- 50µg) are recommended for use as a booster vaccine, and both are considered equally acceptable. AstraZeneca can be used for people who have contraindications to the Pfizer and Moderna vaccines.
- ATAGI recommends that anyone aged 12 or older who is unvaccinated should receive a COVID-19 vaccine as soon as possible.
Background and considerations
ATAGI has been closely monitoring the epidemiology and characteristics of COVID-19 caused by the Omicron variant as well as emerging data on the need, potential benefits and optimal timing of a vaccine booster dose to prevent COVID-19 due to this variant. There is now sufficient evidence to support bringing forward the interval from 5 months after the primary course, as recommended on 17 December 2021, to 4 months and when capacity permits, to 3 months, in order to provide greater protection, particularly for higher-risk groups.
Epidemiology of COVID-19 due to the Omicron variant
The Omicron variant was first designated a variant of concern on 26 November 2021. Since then, large numbers of cases have been reported in many countries where the Omicron variant is now dominant. The rapid growth in case numbers relative to the Delta variant, as well as studies of contacts of cases demonstrating its higher secondary attack rate provide evidence that Omicron can spread rapidly even in populations where there has been widespread infection and/or COVID-19 vaccination.
In Australia, case numbers of Omicron have continued to increase sharply. As of 22 December 2021, 547 confirmed cases due to the Omicron variant have been reported in Australia, but a substantial number of suspected unconfirmed cases are also likely to be due to the Omicron variant (awaiting confirmation via sequencing). In New South Wales, the Omicron variant is thought to be dominant in all regions, and community transmission of the Omicron variant is occurring in all jurisdictions apart from Western Australia.
A preliminary analysis of superspreading events in New South Wales involving the Omicron variant has suggested very low vaccine effectiveness, with the proportion of cases who received two doses of vaccine similar to the proportion of other attendees at the venue who were not infected. Notably, these events involved younger people, the majority of whom received two doses of vaccine relatively recently.
Anticipated benefits of an earlier booster dose for protection against COVID-19 due to Omicron
An earlier booster dose is expected to reduce the risk of symptomatic infection, severe illness and death from COVID-19. In combination with enhanced public health and social measures, it is also expected to mitigate the impacts of COVID-19 on the health system and its the broader impacts on the community.
Preventing symptomatic disease
Strong evidence suggests that booster doses of COVID-19 vaccines may enhance protection against symptomatic disease due to the Omicron variant. This is primarily based on in vitro studies of neutralising antibodies demonstrating that the decreased binding seen with the Omicron variant compared with ancestral strains can be overcome by increasing antibody concentrations with a booster dose. Multiple studies have shown a 2 to >20-fold decrease in neutralising antibody titre against Omicron compared with wild type and/or Delta variant in sera after the primary vaccination course. Studies demonstrate that neutralising antibody titres are higher against Omicron following a booster dose of an mRNA vaccine.1,2
A mathematical modelling study has examined the relationship between neutralising antibody titres and vaccine effectiveness estimated in epidemiological studies. The investigators predicted that six months after primary immunisation with an mRNA vaccine, efficacy for Omicron is estimated to have waned to around 40% against symptomatic disease, and 80% against severe disease (36.7% [95% CI: 7.7-73], 70.9% [95% CI: 32.9-91.5] and 81.1% [95% CI: 42.1-96] for the AstraZeneca, Pfizer and Moderna vaccines, respectively). A booster dose with an mRNA vaccine has the potential to increase efficacy for Omicron to 86.2% (95% CI: 72.6-94%) against symptomatic infection and 98.2% (95% CI: 90.2-99.7%) against severe infection.3
A recent pre-print study from the UK suggested that protective effectiveness against symptomatic COVID-19 due to the Omicron strain was not observable after 2 doses of the AstraZeneca vaccine and was only approximately 35% at about 4 to 6 months (from 15 weeks onwards) after 2 doses of the Pfizer vaccine. Although the number of cases who had received booster doses was small (10 cases receiving a booster after primary AstraZeneca vaccination and 16 cases after primary Pfizer vaccination), the protective effectiveness against symptomatic disease was estimated at about 70–75% after receiving a Pfizer booster dose for both groups.4 Further data from the UK and Europe comparing vaccine effectiveness against the Omicron and Delta strain are anticipated in coming weeks.
Reducing transmission of SARS-CoV-2 in the community
The effectiveness of a booster dose to prevent onward transmission of Omicron from infected persons, and the duration of protection afforded by a booster are currently unclear. It is expected a reduction in symptomatic infection will parallel a reduction in transmission. ATAGI will continue to closely monitor emerging data regarding these evidence gaps.
Reducing severe COVID
Despite key uncertainties, it is reasonable to assume that protection against severe disease is likely to be enhanced by a booster dose, particularly in those with risk factors for severe COVID-19. However, it is not yet known to what degree boosters may provide additional protection against severe disease, hospitalisation or intensive care admissions.
Firstly, the severity of COVID-19 caused by the Omicron strain is not yet known. Early data from South Africa suggest that the odds of hospitalisation with Omicron are around 80% lower than that observed in previous waves.5 Similar data from Scotland suggest that the risk of hospitalisation due to Omicron is reduced by two-thirds compared to Delta.6 It should be noted that in these countries, some protection may have been provided by infection with previous strains, which may limit the generalisability of these findings to Australia where prior infection is much less common. However, high case numbers would still translate into substantial numbers of hospitalisations even if Omicron causes much less severe disease than Delta.
Second, protection against severe disease is generally higher than against symptomatic infection. The modelling study discussed above validated neutralising antibody titres against vaccine effectiveness against symptomatic infection 3. This study suggests that protection against severe disease due to Omicron is also likely to be significantly impaired, particularly when waning protection over time is accounted for, and would be restored by a booster dose of an mRNA vaccine.
Reducing impacts on the healthcare system
Mathematical modelling of the Australian context also suggests that maximising booster doses for all adults may contribute to mitigating the peak number of severe cases of COVID-19 due to Omicron expected in the coming few months. When expanded (and earlier) delivery of booster doses are used in combination with more extensive public health and social control measures, the most major impacts of Omicron on severe health outcomes and on the Australian healthcare system could be mitigated.
Reduced illness in healthcare workers would also be expected to preserve the capacity of the healthcare system to deliver services. Similarly reduced illness in the community would mitigate against the broader impacts of disease caused by the highly transmissible Omicron variant.
Safety of a booster dose given 3 months after a primary course
Common adverse events
Local and international data provide reassurance that booster doses are well tolerated and safe.
There are now considerable data characterising the expected systemic and local adverse event profile in countries where boosters have been administered after 5-6 months. The AusVaxSafety active surveillance system has collated data from more than 92,000 respondents who received booster doses. In this system, the proportion reporting common systemic and local reactions were similar after the booster dose compared with after the second primary dose. No safety issues of concerns have been noted in the USA where millions of booster doses of mRNA vaccines have been administered. Local and systemic reactions and health impacts were reported less frequently following a booster dose than dose 2 of the primary series, and the nature of these reactions were similar to those after a primary series.7
There are more limited data on the expected adverse events when boosters are administered earlier than 5 months. A UK study found that AstraZeneca, Moderna and Pfizer COVID-19 vaccines given as booster doses around 3 months after a primary course of either the AstraZeneca or Pfizer vaccine were all generally well tolerated.8 The most common systemic reactions for all booster vaccines were fatigue and headache, and the most common local reaction was injection site pain. Adverse events were more common in those who received a Moderna booster (compared with a Pfizer booster), in those who had a different brand of booster vaccine than what was used for the primary course (compared with those who had the same vaccine brand for all doses), and in younger (compared with older) participants.
Vaccine associated myocarditis
The impact of reducing the interval between the primary course and booster dose to 3 months on the risk of myocarditis is not yet known. Data from the UK, where more than 21 million booster doses have been administered, have not identified any new safety signals.9
It should be noted that myocarditis appears to be more common after second doses in younger males. As of 12 December 2021, the overall rate of myocarditis for all ages reported to the Therapeutic Goods Administration (TGA) is 1.6 (95% CI 1.5 – 1.7) per 100,000 doses of Pfizer COVID-19 vaccine and 2.5 (95% CI 1.8 – 3.3) per 100,000 doses of Moderna COVID-19 vaccine given. Preliminary data from people who received a Pfizer booster vaccine at least 5 months after a Pfizer primary course suggest that the risk of myocarditis is not higher after the booster dose than after the second dose.10
There are currently no data on the risk of myocarditis after a booster dose of the Moderna vaccine, but this is expected to be available in coming weeks. More information on myocarditis and pericarditis after mRNA vaccines is available here.
Implications for the rollout program and Omicron control
ATAGI does not anticipate that shortening the booster interval alone will be sufficient to suppress the rapid spread of the Omicron variant, and additional non-pharmaceutical public health measures are likely to be required to prevent continued rapid growth in case numbers.
As a result of the shortened recommended interval between the COVID-19 primary course and booster dose, a large number of people are currently eligible or will soon become eligible for a booster dose. Currently, around 4 million people are eligible for boosters at 5 months; this would increase to around 7.2 million if the eligibility interval was brought forward to 4 months, and to 11 million if brought forward to 3 months. ATAGI is conscious of the burden of a sharp increase in demand will have on immunisation service providers, particularly over the holiday period. Bringing forward eligibility in stages, initially from 5 months to 4 months, then later to 3 months will achieve the goal of maximising booster coverage as quickly as possible. However, it will also implicitly prioritise the higher risk populations who received their primary vaccines first. ATAGI recommends that all possible measures be undertaken to facilitate timely access to a booster dose for people with increased risk of severe disease, i.e., provide enhanced direct protection. ATAGI recognises some flexibility may be required for operational reasons, particularly in high-risk settings such as remote communities and within aged/disability care facilities.
Uncertainties and evidence gaps
As noted above, the severity of disease caused by the Omicron variant remains uncertain. While few people have been hospitalised with COVID-19 due to Omicron in Australia to date, this may reflect the expected lag between diagnosis and progression to severe disease; it may also reflect the younger population in whom the Omicron variant was first detected.
There is still little evidence on the incremental benefit of booster doses in protecting against severe disease or reducing onward transmission of Omicron variant of SARS-CoV-2, and on the duration of protection provided by COVID-19 booster doses.
ATAGI will continue to closely monitor the situation and review data that informs these key evidence gaps and will update recommendations accordingly.
- Nemet, I., et al. (2021). "Third BNT162b2 vaccination neutralization of SARS-CoV-2 Omicron infection." medRxiv: 2021.2012.2013.21267670. Available from: https://www.medrxiv.org/content/10.1101/2021.12.13.21267670v1
- Garcia-Beltran, W. F., et al. (2021). "mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant." medRxiv: 2021.2012.2014.21267755. Available from: https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1
- Khoury, D. S., et al. (2021). "A meta-analysis of Early Results to predict Vaccine efficacy against Omicron." medRxiv: 2021.12.1213.21267748. Available from: https://www.medrxiv.org/content/10.1101/2021.12.13.21267748v2
- Andrews, N., et al. (2021). "Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern." medRxiv: 2021.2012.2014.21267615. Available from: https://www.medrxiv.org/content/10.1101/2021.12.14.21267615v1
- Wolter, N., et al. (2021). "Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa." medRxiv: 2021.2012.2021.21268116 Available from: https://www.medrxiv.org/content/10.1101/2021.12.21.21268116v1
- Sheikh, A., et al. (2021). "Severity of Omicron variant of concern and vaccine effectiveness against symptomatic disease: national cohort with nested test negative design study in Scotland." University of Edinburgh Research Explorer. Available from: https://www.pure.ed.ac.uk/ws/portalfiles/portal/245818096/Severity_of_Omicron_variant_of_concern_and_vaccine_effectiveness_against_symptomatic_disease.pdf
- Shimabukuro T. COVID-19 Vaccine safety updates Advisory Committee on Immunization Practices (ACIP) June 23, 2021 [Internet]. 2021 [cited 2021 Dec 21]. Available from: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/03-COVID-Shimabukuro-508.pdf
- Munro, A. P. S., et al. (2021). "Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial." Lancet 398(10318): 2258-2276. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02717-3/fulltext
- UK Government Medicines & Healthcare products Regulatory Agency. Coronavirus vaccine - weekly summary of Yellow Card reporting: Updated 16 December 2021 [Internet] Published 16 December 2021 [Cited 2021 Dec 23] Available from https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting
- Israeli Ministry of Health, Weizmann Institute of Science, Gertner Institute, Hebrew University & Technion. Food and Drug Administration, Vaccines and Related Biological Products Advisory Committee October 14-15, 2021 Meeting Presentation: Booster protection across ages - data from Israel. 2021. Available from: https://www.fda.gov/media/153086/download