Public health considerations and evidence to support decisions on the implementation of a second mRNA COVID-19 vaccine booster dose

Key messages

• Following the rise to dominance of the SARS-CoV-2 Omicron variant in January 2022, transmission and burden of severe disease among older age groups increased to very high levels, although this has recently started to decline in most European Union/European Economic Area (EU/EEA) countries. It remains uncertain whether, in the coming weeks/months, these indicators will stabilise at the low inter-wave levels observed prior to Omicron, or at an elevated plateau.
• Since completeness of vaccination status in COVID-19 cases reported to the European Surveillance System (TESSy) is limited, we are unable to attribute the observed increases in severe disease due to Omicron to individuals with a particular level of vaccination. However, a separate analysis of three countries with complete data on severe outcomes and vaccination status demonstrates that the highest burden of severe outcomes has been among unvaccinated people in all adult age groups and this continues to be the case.
• All EU/EEA countries are currently recommending a first booster dose at a defined interval following primary vaccination. At present, uptake of the first booster dose in the EU/EEA adult population is 64.2% (country range 11.0−87.9%).
• In general, vaccine effectiveness (VE) against infection due to Omicron has been shown to be reduced compared to other SARS-CoV-2 variants, and protection wanes over time.
• Published literature indicates VE against severe outcomes caused by Omicron remains high, with continued strong protection in the range of 80−90% around 2−3 months after receiving the first booster, albeit with some evidence of this waning slightly from around 3-4 months. In addition, analysis of severe outcomes among COVID-19 cases having received a first booster dose, as reported to TESSy, also shows that hospitalisation and death are extremely rare in this group; 0.38% and 0.1% respectively. Moreover, the adjusted risk of hospitalisation and death is higher in older populations, males and those who received a first booster dose more than three months ago.
• Evidence currently available indicates that a second mRNA booster dose is able to restore the humoral immune response to levels similar to those observed shortly after the first booster dose, and also to restore VE against infection, although this does appear to wane rapidly. Early data indicate that the risk of severe disease and/or death due to COVID-19 is reduced for up to 10 weeks after the administration of a second booster dose, compared to those receiving only the first booster dose. However, this is in populations already experiencing low levels of severe outcomes, thus providing small absolute reductions. The maximum duration of this protection is not yet known due to the short follow-up periods after the second booster in the studies available.
• Mathematical modelling suggests that increasing the proportion of the population who have been provided with immunity through a primary course and first booster has a substantial potential to reduce COVID-19 death burden by the end of October 2022. This is particularly relevant for countries where gaps in coverage are still large, and efforts to address these gaps remain a public health priority. With regard to the second booster, modelling shows that its roll-out in some vulnerable groups could avert a substantial proportion of COVID-19 deaths between now and mid-autumn 2022. Further indications are set out below.
• The total number of averted deaths, both before and beyond autumn 2022, depends on the COVID-19 incidence, and as such is difficult to predict with certainty.
• To reduce future COVID-19 burden through a second booster, the effect per dose is highest when targeting vulnerable populations, such as older age groups.
• Given that vaccination and the boosting of immunity achieves the maximum impact at population level if administered before an epidemic wave and the minimum impact if administered at the end of an epidemic wave, a continuous high incidence or a large surge in cases in the early summer would imply greater benefit could be achieved by an early second booster roll-out. Alternatively, if surveillance shows relatively low incidence levels during the summer months, the optimal timing for a second booster roll-out would be later in the year, subject to further assessment of the risk of a surge in cases during autumn/winter 2022 and waning protection against severe outcome.
• Given data on the current epidemiological situation, vaccine effectiveness and mathematical modelling, it is suggested that EU/EEA countries consider the information set out below with respect to the administration of a second COVID-19 booster dose.
• Due to the fragility of the population, continued high hospitalisation and ICU rates in many settings, lower immune response to vaccination, and the higher risk of severe COVID-19, the public health benefit of administering a second booster dose is clearest in those aged 80 years and above. Immediate administration of a second booster dose in this population would be optimal in situations of continued high or increasing viral circulation. Alternatively, in situations of low viral circulation, administration of a second booster dose should be considered prior to autumn 2022.
• Mathematical modelling suggests that a second booster roll-out including those aged 60-79 years who are immunocompetent in the EU/EEA is likely to be beneficial, although the best timing for the roll-out depends on the highly uncertain future of COVID-19 incidence. Therefore, continued close epidemiological and vaccine effectiveness monitoring is essential in order to rapidly detect signals of increased SARS-CoV-2 circulation or risk of severe COVID-19 among vaccinated individuals. If such signals emerge, a second booster may be considered for all or some adults between the ages of 60 and 79 years and countries should have plans in place for a rapid deployment of booster doses in this population group.
• For immunocompetent individuals below 60 years of age, the administration of a second booster dose at this time is not supported by the current epidemiological, modelling or VE data on the continued level of vaccine protection against severe disease or death.
• Continued protection against severe disease will need to be monitored in those populations receiving a second booster dose in spring/early summer 2022 in order to consider the need for additional booster doses in relation to potential future autumn/winter 2022 waves.
• Adapted vaccines may potentially be authorised later in the year and could be taken into account with regard to the timing of a second booster dose.
• It remains essential that countries have strong surveillance systems to detect increased incidence, severity, and emerging variants of concern coupled with preparedness planning to quickly implement booster dose campaigns if deemed necessary.
• Communication planning should consider when the efforts to promote uptake of the second COVID-19 booster dose are likely to be most effective. At this stage, focus should be on targeted communication for those population groups who are recommended a second booster, whilst also ensuring full vaccination and uptake of the first booster in those most at risk of severe disease who have not yet completed their recommended vaccinations.
• In anticipation of possible new waves and the related need to adapt recommendations around a second booster dose (e.g. extending them to other age groups), planning of future campaigns should be based on good practices to promote vaccine acceptance and uptake identified during earlier phases of the vaccination programme, and taking into account behavioural insights research.
• Depending on the evolving epidemiology and forthcoming data on vaccine effectiveness over time, it will be necessary to re-assess recommendations on timing and with regard to the populations that may benefit from a second COVID-19 vaccination booster dose in the near future.