Efficacy, Effectiveness and Safety of Vaccines Against COVID-19 for Children Aged 5-11 Years: A Living Systematic Review with Meta-Analysis

Background: To date, more than 628 million confirmed SARS-CoV-2 infections were recorded globally. Highest incidences were usually observed in school-aged children.Methods: The aim of this living systematic review is to evaluate vaccine efficacy/effectiveness (VE) and safety of COVID-19 vaccines approved in the European Union for children aged 5-11 years. In this version, we included studies of any design identified through searching the COVID-19 L·OVE (Living OVerview of Evidence) platform up to 13 September 2022. We assessed risk of bias and rated the certainty of evidence (CoE) using GRADE.Findings: In total 4,651 records were screened and 30 studies were included. The studies assessed two mRNA vaccines (BNT162b2 or mRNA-1273), with pivotal randomized controlled trials (RCTs) being conducted before and all other studies during the Omicron era.VE against pre-Omicron variant SARS-CoV-2 infections was 73·0% (41%-87%, 1 RCT, CoE: moderate), while VE against Omicron variant SARS-CoV-2 infections was 41·9% (27·4%-53·5%, 6 non-randomized studies of interventions [NRSIs], CoE: moderate). Pre-Omicron VE against symptomatic COVID-19 was 86·7% (58·1-95·8%, 2 RCTs, CoE: moderate) and 38·7% (21·7%-52·1%, 5 NRSIs, CoE: moderate) after Omicron emergence. No cases of severe COVID-19 were reported in RCTs. VE against Omicron-associated COVID-19 hospitalisation was 75·3% (68·0%-81·0%, 6 NRSIs, CoE: moderate).Safety data suggests no increased risk of serious adverse events (RR 0·83 [0·21-3·33], 2 RCTs, CoE: low), with approximately 1·2 events per 100,000 administered vaccines reported in real-life observations. Evidence on the risk of myocarditis was uncertain (RR 4·6 [0·1-156·1], 1 NRSI, CoE: low), with 0·13-1·04 observed events per 100,000 administered vaccines. The risk of AEs (RR 1·21 [1·07-1·38], CoE: moderate) was higher among mRNA-vaccinated children.Interpretation: In 5-11-year-old children mRNA-vaccines are moderately effective against infections with the Omicron variant, but probably still protect well against COVID-19 hospitalisations. Vaccines were reactogenic but generally safe.Funding Information: This project is funded by the Federal Joint Committee (Gemeinsamer Bundesausschuss) in Germany (G-BA, Funding no.: 01VSF20019).Declaration of Interests: WS was employed at Roche Pharma AG from April 2020 to June 2021. Roche Pharma AG is not involved and has not any influence on this project. All other authors have no financial interests to disclose.Ethics Approval Statement: Ethical approval was not required as this living systematic review is based exclusively on published literature.