A paper in Nature Communications in May 2024 presents the results of a self-controlled case-series study of over 5 million children in England that compared risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. The authors find that SARS-CoV-2 infection was associated with “increased risks” of hospitalisation from seven outcomes. However, these risks were “largely absent” in those who had been vaccinated prior to infection.
Vaccines for children
The authors state that the UK approved COVID-19 vaccination for all children aged 12 and over in September 2021, a decision that was extended to 5-11-year-olds in April 2022 in a one-off programme. Although uptake was “very high” in adults, uptake was lower in children. Most vaccinated children received the Pfizer/BioNTech vaccine. In November 2022 the Joint Committee on Vaccination and Immunisation (JCVI) recommended that 16-49-year-olds who were not in a clinical risk group should no longer be offered a third vaccine dose from February 2023, and that primary course vaccination in 5-49-year-olds should be targeted to groups at high risk of severe COVID-19.
Recognising that the benefits of COVID-19 vaccines in older adults “clearly outweigh the risks of rare complications”, the authors identify an “uncertain” balance of risks and benefits in young people. Although clinical trials have demonstrated the effectiveness of COVID-19 vaccines in reducing the risk of severe COVID-19 in children between the ages of 5 and 15, the absolute risk of severe outcomes after infection is “low”. However, a “serious consequence of SARS-CoV-2 infection in children is multisystem inflammatory syndrome (MIS-C). Another “serious outcome” of infection is post-COVID syndrome, or long COVID.
An identified barrier to COVID-19 vaccine acceptance is concern around vaccine safety, and the study authors acknowledge that an increased risk of myocarditis has been “consistently reported” after the delivery of mRNA vaccines; this has been observed “predominantly” in males aged 18 to 36 and “most notably” after the second dose”. The need to “quantify the overall risks and benefits of COVID-19 vaccination” in the younger age group is “important”, so the authors sought to investigate and compare the risks of pre-specific vaccine safety outcomes following vaccination with BNT162b2, mRNA-1273, and ChAdOX1 in children.
The study
The researchers used the English National Immunisation Management Service (NIMS) database of COVID-19 level to national data for mortality, hospital admissions, and SARS-CoV-2 infection. The self-controlled case series design was used to investigate the association between the three vaccines and hospitalisation with the following pre-specified outcomes:
- Myocarditis
- MIS-C
- Immune thrombocytopenia (ITP)
- Epilepsy
- Acute pancreatitis
- Acute disseminated encephalomyelitis (ADEM)
- Guillain-Barré syndrome
- Appendicitis
- Demyelinating disease
- Myositis
- Angioedema
- Anaphylaxis
The researchers also investigated the association of SARS-CoV-2 infection with these outcomes in children who were vaccinated before infection compared to those who were unvaccinated at time of infection. The total children included in the study was 5,197,925; this comprised 1,842,159 children 5-11 years and 3,355,766 adolescents aged 12-17. A further 4,347,781 young adults, aged 18-24 years, were included as a comparison.
What does the study find?
The authors identify “several key findings” that have relevance to public health policy makers. The first is that there was “no strong evidence for increased risks of any of the 12 safety outcomes investigated” after COVID-19 vaccination in children aged 5-11 years. The second is that, in adolescents between the ages of 12 and 17, there was an increased risk of hospital admission for myocarditis after a first or second dose of BNT162b2 and an increased risk of hospitalisation with epilepsy and demyelinating disease (in females only) following a second dose of BNT162b2.
“Children and adolescents aged 5-17 years who had not received a COVID-19 vaccine dose prior to SARS-CoV-2 infection had an increased risk of hospitalisation from seven of the pre-specified safety outcomes including MIS-C and myocarditis.”
Furthermore, the risks of safety outcomes from SARS-CoV-2 infection were “largely absent” in 5-17-year-olds who had received at least one COVID-19 vaccine dose prior to infection. In children aged 5-11 who had not been vaccinated against COVID-19 prior to infection, the authors observed increased risks of hospital admission from MIS-C, myocarditis, acute pancreatitis, myositis, and ADEM. These risks were “absent” in both children and adolescents who had received at least one dose of a COVID-19 vaccine prior to infection; the exception to this was hospitalisation with epilepsy.
“This study has shown that vaccination is associated with a significantly reduced risk of most SARS-CoV-2 complications in young people, particularly MIS-C, which can be fatal.”
The researchers conclude that there was “no strong evidence for increased risks” of the 12 pre-specified vaccine safety outcomes following vaccination against COVID-19 in children aged 5-11 years. By contrast, in unvaccinated children, they found “increased risks of hospitalisation from seven adverse outcomes” that were either not observed or reduced after vaccination.
“Overall, our findings support a favourable safety profile of COVID-19 vaccination using mRNA vaccines in children and young people aged 5-17 years.”
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