ATAGI recommendations on use of Covid vaccines in all young adolescents in Australia

Summary of ATAGI recommendations

• Vaccination against COVID-19 is recommended for all individuals from 12 years of age, extending the current recommendation for those aged 16 years and older.
• A two-dose schedule using Comirnaty (Pfizer), the only vaccine currently registered for use in Australia in this age group, is recommended.
• Recommendations on the use of Spikevax (Moderna) for adolescents will be finalised following the decision on provisional registration of Spikevax (Moderna) in this age group.

Introduction

The Australian Technical Advisory Group on Immunisation (ATAGI) recently recommended vaccination using Comirnaty (Pfizer) for adolescents from

12 years of age that belong to the following groups¹:

• Individuals with specified medical conditions that increase their risk of severe

  COVID-19, including NDIS participants

• Aboriginal and Torres Strait Islander individuals

• Those in remote communities, as part of broader community outreach vaccination programs.

The Therapeutic Goods Administration (TGA) registration of Comirnaty was extended on

23 July to include all people from 12 years of age and above in a two-dose schedule. At present COVID-19 vaccine AstraZeneca (Vaxzevria) and Spikevax (Moderna) are provisionally registered for use in individuals aged ≥18 years. Spikevax (Moderna) vaccine is under consideration for provisional registration by TGA for 12 to 17 year olds with a decision anticipated by early September 2021. Some data on Spikevax (Moderna) in adolescents are included in this advice.

ATAGI has developed these current recommendations for all individuals aged 12 years and above by carefully considering the relevant benefits, risks, uncertainties and evidence on the following:

• Safety, efficacy and effectiveness of COVID-19 vaccines in adolescents from clinical trials and overseas vaccination programs

• Epidemiology of COVID-19 in adolescents including disease severity and complications, and their role in transmission in the population
• Safety of COVID-19 vaccines, including risk of myocarditis and pericarditis after receiving mRNA vaccines in adolescents and young adults reported overseas
• Programmatic implications and the potential delivery strategies to extend vaccination to the young adolescent age group
• Mathematical modelling relating to population level impact of vaccinating this age group
• Evidence of potential acceptance of vaccination in this age group.

Benefits of vaccinating adolescents against COVID-19

Direct benefits against COVID-19 in children:

Vaccine efficacy, immunogenicity and effectiveness: There is high level evidence indicating strong immunogenicity and vaccine efficacy against symptomatic COVID-19 in adolescents from clinical trials of Comirnaty (Pfizer) and Spikevax (Moderna). In results of an ongoing phase III Comirnaty trial with over 2,000 participants aged 12-15 years, vaccine efficacy against symptomatic COVID-19 from 7 days after dose two was 100% (95% CI 78.1-100%) with no cases reported in the vaccine arm.² After dose one and before dose two, there were 3 COVID-19 cases (within 11 days after dose one) among Comirnaty recipients compared with 12 cases in the placebo group resulting in vaccine efficacy of 75% (95% CI, 7.6 to 95.5%). Neutralising antibody titres post dose two were 1.8-fold higher in the 12-15 years age group compared to 16-25 years age group.

In the ongoing phase II/III trial of Spikevax (Moderna) that recruited approximately 4,000 participants aged 12-17 years, vaccine efficacy against symptomatic COVID-19 from 14 days after dose two was 93.3 % (95% CI 47.9 to 99.9%).³ Immunogenicity of Spikevax (Moderna) (measured by pseudotyped virus neutralisation assay) in the 12-17 year age group compared to the 18-25 year age group met pre-determined non-inferiority criteria in terms of antibody titres and seroresponse rates.

Data on vaccine effectiveness among adolescents against any COVID-19 clinical outcome are limited. One interim report from the Ministry of Health of Israel, where Comirnaty has been used in adolescents aged 16 -18 years since January 2021 reported vaccine effectiveness of 98% against both symptomatic infection (95% CI, 96 to 99%) and hospitalisation (95% CI, 83 to 100%) with no deaths among the vaccinated.⁴

Disease burden in adolescents: Vaccinating adolescents is anticipated to prevent

SARS-CoV-2 infections, hospitalisations and deaths due to COVID-19, and other complications such as Paediatric Multisystem Inflammatory Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) and long COVID-19. Although the severity of COVID-19 is less in adolescents (with approximately 4-7% experiencing severe outcomes) compared with adults, adolescents appear to have infection rates similar to adults.^5,6 The SARS-CoV-2 Delta Variant of Concern (VoC) has demonstrated increased transmissibility across all age groups and is associated with an increased risk of developing COVID-19 for adolescents in the absence of vaccination.⁷ Potential new VoCs may also pose a greater risk to non-immune children and adolescents in the future. In the many countries experiencing Delta variant transmission, including in Australia, the median age of people with COVID-19 is falling with adolescents and children accounting for a higher proportion of disease in the context of vaccinated older age groups. Overall hospitalisation rates for COVID-19 in the adolescent age group are higher than for other diseases such as influenza. In the USA, COVID-19 hospitalization rates in adolescents from October 2020 to April 2021 were

2.5-3.0 times higher than that for influenza-associated hospitalization rates from three recent influenza seasons.⁸

In Australian COVID-19 national notification data (NNDSS) for 1 January to 1 August 2021, 13.4% of cases were aged 10-19 years.⁹ In New South Wales data for the period 2 July to 19 August from the current Delta variant outbreak about 18% of cases were in the 10-19 years age group (about 6% in 12-15 years age group)[1]. During the period 16 June to

17 July 2021, the rate of COVID-19 in the 12-17 years age group residing in Southwestern Sydney local health districts was approximately 200 per 100,000. This was similar to that seen in young adults (18-29 years; approximately 260 per 100,000) who had the highest incidence of all age groups.¹⁰ The proportion of hospitalisations was markedly less in adolescents compared to adults nationally and this has been seen consistently throughout the COVID-19 pandemic. In hospitalisation data from selected jurisdictions (where admission for disease severity rather than for isolation purposes occurs) the proportion of adolescent cases notified from 1 January to 1 August 2021 that required hospitalisation was 2.9%, and ICU admission was 0.6%. Of the total 910 deaths due to COVID-19 captured in NNDSS from 13 January 2020 to 19 May 2021, there were none in persons under 20 years of age; deaths in children and adolescents have also been seen rarely in the UK and USA (about 0.06% out of all deaths due to COVID-19).^11,12

Benefits to the broader population relating to COVID-19:

Vaccinating adolescents is anticipated to contribute to a reduction in SARS-CoV-2 transmission in the broader population. Once a large proportion of adults are vaccinated, susceptible children and adolescents will account for a higher proportion of continued infections in the community contributing to transmission. This has been seen in countries such as Israel and the USA.^13,14

While there is some uncertainty regarding the relative contribution by adolescents to the transmission of SARS-CoV-2 in the wider community, studies published in 2020 exploring SARS-CoV-2 spread within family clusters have reported children as index cases in about 4% of households.¹⁵ Data from primary care and household studies suggest that

SARS-CoV-2 is mainly spread between adults and from adult family members to children.¹⁶ In schools this pattern is also seen most commonly, however transmission between adolescents in school settings has also been well documented. Vaccination of adolescents would likely contribute to reducing school-based transmission.¹⁷ Many of these studies were conducted prior to detection of the Delta and other VoCs with higher transmissibility, suggesting even greater benefit from vaccination.

Other benefits:

Vaccinating adolescents is anticipated to reduce disruption to their education by preventing disease and reducing potential transmission and outbreaks in schools. Prolonged absence from face-to-face learning in school can have considerable psychosocial and educational impacts on children, and vaccination of all adolescents (alongside vaccination of school staff) offers benefit in mitigating against this.¹⁸

A reduction in the number and severity of outbreaks resulting in school closures and extensive public health interventions would also likely reduce disruption to parents' and family work with clear economic benefits.

Vaccinating adolescents would also likely result in less disruption to sports, other organised activities and socialising that are key to adolescent physical and mental wellbeing.

Wellbeing may also be enhanced by adolescents not being implicated in spread of the virus to others in the community (e.g. elderly or immunocompromised) who may still experience poor health outcomes, even if vaccinated. Protection of adolescents may thus have a wider impact on mental health and well-being of them, their family and the community.

Risks relating to vaccine adverse events

In the Comirnaty phase II/III clinical trial in adolescents, local and systemic adverse events within seven days following vaccination were frequently reported but were generally mild to moderate in severity and typically resolved within 1-2 days.² One in five adolescents developed fever (≥38°C) after the second dose. In the phase II/III Spikevax (Moderna) clinical trial, local reactions occurred in over 90% of participants 12-17 years of age after each dose but were mostly mild and transient.³

COVID-19 vaccine safety surveillance using the V-safe system in the USA has collected data for 0-7 days after Comirnaty dose one (over 57,000 persons) and dose two (about 16,000 persons) in adolescents aged 12-15 years as of 13 June 2021.¹⁹ As expected from clinical trial data, injection site pain was the most frequently reported adverse event after dose one (~60%) and dose two (~62%). The proportions of individuals that required medical care in an emergency department or hospital in 12-15 years age group were similar to that in the 16-25 years age group (0.1% after dose one and 0.2% after dose two).

These data on safety of Comirnaty (Pfizer) and Spikevax (Moderna) from clinical trials and safety surveillance overseas affirm that the overall good safety profile in the adolescent age group is similar to that in adults. In the USA, approximately 7 million adolescents aged 12-15 years and 4 million aged 16-17 years have now received at least one dose of Comirnaty.²⁰

Myocarditis and pericarditis following mRNA vaccines:

Since April 2021, myocarditis and pericarditis have been reported in temporal association following COVID-19 vaccination with Comirnaty (Pfizer) and Spikevax (Moderna). Data suggest these conditions are causally related to vaccination with a COVID-19 mRNA vaccine although the exact mechanism is not clear and no risk factors have been identified. The risk appears highest in young people (adults post-vaccination observation time) in males aged 12-17 years was 10 cases per million for dose one and 67 cases per million for dose two.¹⁹ The vast majority of these cases have been mild and patients have recovered quickly with supportive care. More precise data on the vaccine-attributable risk of myocarditis and pericarditis, including any potential differences by mRNA vaccine brand, are awaited, particularly from settings such as the USA and Canada.

ATAGI advice on the benefits of vaccination with Comirnaty compared with risks of myocarditis/pericarditis and the clinical management of these conditions after vaccination was issued on 30^th July 2021.²¹ This advice pertains to individuals aged 16 years and above. There is currently no evidence to suggest that the rate or severity of myocarditis or pericarditis in individuals 12-15 years old is different to that in older adolescents or young adults. This advice also specified the use of the registered two-dose schedule. While noting that the risk of myocarditis appears increased post dose two of an mRNA vaccine, ATAGI considers that the second vaccine dose is needed to ensure optimal protection and duration of immunity. There are no data currently on whether the risk of myocarditis differs depending on the time interval between doses; as such, a routine interval of 3-6 weeks between Comirnaty doses is recommended.

More data are anticipated to be available soon on the risk, severity and longer-term outcomes of myocarditis and pericarditis in adolescents following both mRNA vaccines (Comirnaty [Pfizer] and Spikevax [Moderna]) and this will inform ongoing ATAGI recommendations and benefit-risk assessment.

Programmatic and other considerations regarding vaccinating adolescents against COVID-19

The current constraint on vaccine supply is a key determinant on the timing of delivery of an adolescent COVID-19 vaccination program. Recent modelling suggests greater population-level benefit from increasing vaccination coverage among adults aged 20 to 39 years of age (rather than adolescents) given their greater role in disease transmission.²² Therefore, in the context of constrained vaccine supply, delivery of a population-wide adolescent program should not be prioritised over vaccination to younger adults in most contexts. ATAGI understands that further modelling exploring schools as a specific risk setting, which would be relevant to vaccinating the adolescent population, is underway.

ATAGI recommends that vaccination of 12-15 year age group is of a lower priority than older adults (as the direct benefits of vaccination in preventing severe COVID-19 are greatest in this group). ATAGI therefore recommends that all strategies are considered including provision of choice of vaccine to ensure older adults are vaccinated. Vaccination still does benefit children by preventing COVID-19 and its complications, and in lowering the risk of school disruption, although their contribution to community transmission is thought to be less than in adults.

Flexible use of a combination of strategies implemented sequentially and/or concurrently, will assist in providing access to COVID-19 vaccine to adolescents and their families. Certain strategies may be more appropriate in some settings or jurisdictions. Potential strategies to deliver COVID-19 vaccine to adolescents include: school-based program delivery; mass vaccination using existing or new hubs (e.g. suitable schools or other community settings); delivery via primary care (e.g. GPs and pharmacists where jurisdictional regulations permit). Utilising the infrastructure established for COVID-19 vaccination of adults can readily be adapted to adolescents in many cases. ATAGI understands that early consultation with jurisdictions to assist in identifying optimal strategies to deliver COVID-19 vaccines to adolescents is underway.

Although school-based vaccination is a good access point for routine NIP vaccines for adolescents, limitations in surge workforce capacity and the relatively longer lead time required for implementation and planning means delivery of a COVID-19 school-based program within the 4th quarter of 2021 may not be feasible in many jurisdictions. Delivery of COVID-19 vaccine through a school-based program in 2022 also presents implementation challenges and risks to potentially disrupt the routine school vaccination program. However, schools could potentially be set up as temporary mass vaccination sites, utilising existing infrastructure for mass vaccination delivery, in conjunction with other modes of delivery.

A more detailed review and advice from ATAGI regarding various options for implementing a potential adolescent vaccination program is currently being drafted and will be provided to the COVID-19 Vaccine Taskforce.

Uptake of COVID-19 vaccine in young adolescent age groups in other countries:

In the USA the Advisory Committee on Immunisation Practices (ACIP) recommended extending the use of Comirnaty (Pfizer) to all adolescents 12-15 years of age in mid-May 2021. As of August 20 2021, the vaccine coverage in that age group is 45% for dose one and 33% for two doses. Among older adolescents 16-17 years of age coverage estimates are 58% for dose one and 43% for two doses.²³ In Israel, where vaccinating adolescent aged 12-15 years commenced in early June, approximately 40% of adolescents have received at least one dose of the vaccine.¹³ In Canada, in the 12-17 years age group, as of the 14 August 2021, 76% have had a single dose and 59% two doses.²⁴

While a similar or ultimately higher final rate of vaccine uptake among adolescents in Australia would be anticipated, achieving high uptake would be assisted by ensuring information needs of both parents and adolescents, as well as immunisation providers, are met, and informed using an Australian specific evidence-base, such as surveys of parents' and adolescents' attitudes, knowledge and intended position on COVID-19 vaccination.

Conclusions

ATAGI concludes that the benefits of offering COVID-19 vaccination to all younger adolescents aged 12-15 years outweigh the known or potential risks. As such, ATAGI recommends inclusion of this age group in the Australian COVID-19 vaccination program over time.

COVID-19 epidemiology in this age group is rapidly evolving with younger age groups more implicated in transmission in the context of the more transmissible Delta variant. With older age groups increasingly protected by vaccination, a greater proportion of COVID-19 is anticipated to occur in adolescents and children. While supply of Comirnaty (Pfizer) (and Spikevax [Moderna] if TGA registered and ATAGI recommended in this age group) remains constrained, the timing of inclusion of adolescents in the national COVID-19 vaccination program needs to be balanced against access to these vaccines in other priority populations. Delivery of the program will require tailoring access and services to adolescents in the local context; use of a combination of strategies, determined in close consultation with jurisdictions.

Data on vaccine safety in the adolescent age group are still accumulating, particularly on the risk of myocarditis and pericarditis following mRNA vaccines. However, the risk for these conditions and risk of any severe outcomes appears very low. ATAGI will continue to review the data and update recommendations iteratively, but believe that the many benefits of offering the registered two-dose Comirnaty vaccination schedule outweighs the risks for all children and adolescents aged 12 years and older

[1] Based on publicly available NSW health COVID-19 case counts (Link) and data provided to NCIRS by NSW Ministry of Health

References

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