Safety and effectiveness of COVID-19 mRNA vaccination and risk factors for hospitalisation caused by the omicron variant in 0.8 million adolescents: A nationwide cohort study in Sweden

Abstract

BackgroundReal-world evidence on the safety and effectiveness of COVID-19 vaccination against severe disease caused by the omicron variant among adolescents is sparse. In addition, evidence on risk factors for severe COVID-19 disease, and whether vaccination is similarly effective in such risk groups, is unclear.Methods and findingsNationwide registers were used to examine the safety and effectiveness of COVID-19 mRNA vaccination against COVID-19 hospitalisation, and risk factors for COVID-19 hospitalisation in adolescents. The safety analysis included all individuals in Sweden born between 2003-2009 (aged 11.3-19.2 years) given at least one dose of mRNA vaccine (N=645,355), and never vaccinated controls (N=199,022). Outcomes evaluated included all hospitalisations until 5 June 2022. The vaccine effectiveness (VE) against COVID-19 hospitalisation and associated risk factors was evaluated in adolescents given two doses of mRNA vaccine (N=501,945), as compared to never vaccinated controls (N=170,083), during an omicron predominant period (1 January 2022 to 5 June 2022). The safety analysis showed that COVID-19 mRNA vaccination was not associated with an increased risk of any serious adverse events resulting in hospitalisation. During follow-up, 1.69% of the vaccinated individuals were hospitalised compared to 1.71% of the controls (P=0.29). In the VE analysis, there were 21 cases (0.004%) of COVID-19 hospitalisation among 2-dose recipients and 26 cases (0.015%) among controls, resulting in an estimated VE of 75% (95% CI, 54-86, P<0.001). Strong risk factors for COVID-19 hospitalisation included previous infections (odds ratio [OR], 14.3, 95% CI, 7.7-26.6, P<0.001), and cerebral palsy/development disorders (OR, 12.0, 95% CI, 6.4-22.6, P<0.001), with similar estimates of VE in these subgroups as in the total cohort. The number needed to vaccinate with two doses to prevent one case of COVID-19 hospitalisation was 9,007 in the total cohort and 1,031 in those with previous infections or developmental disorders. None of the individuals hospitalised due to COVID-19 died within 30 days.ConclusionsIn this nationwide study, COVID-19 mRNA vaccination was not associated with an increased risk of any serious adverse event in adolescents. Two doses were associated with a lower risk of COVID-19 hospitalisation during the omicron predominant period, especially among those with certain predisposing conditions who should be prioritized for vaccination. However, COVID-19 hospitalisation among general adolescents was extremely rare, and additional doses in this population may not be warranted at this stage.Why was this study doneEvidence before this study➢There is limited evidence on the effectiveness of COVID-19 vaccination against severe outcomes during the omicron era among adolescents. In addition, there is lack of data on whether certain groups of adolescents are at greater risk of severe COVID-19 and should be prioritized in vaccination programs, and whether vaccination is equally effective in such risk groups.➢Regarding safety, some studies have indicated a link between COVID-19 mRNA vaccination and increased risk of myocarditis and pericarditis in young men, although the data appear inconsistent.What did the researchers do and find?➢Using Swedish nationwide health registers, a cohort of 844,377 adolescents were followed until 5 June 2022 to evaluate the safety and effectiveness of COVID-19 mRNA vaccination against COVID-19 hospitalisation, and risk factors for COVID-19 hospitalisation.➢COVID-19 mRNA vaccination in adolescents was not associated with an increased risk of any diagnoses resulting in hospitalisation. In contrast, two doses of vaccine had an associated 75% effectiveness against COVID-19 hospitalisation. However, only about 6 individuals in 100,000 were hospitalised due to COVID-19 during follow-up.➢There were certain strong risk factors for COVID-19 hospitalisation, such as previous infections and different development disorders, which increased the risk of COVID-19 hospitalisation more than tenfold. Vaccine effectiveness among these individuals was similar as in the rest of the cohort.What do these findings mean?➢Although COVID-19 mRNA vaccination appears safe and associated with reduced risk of COVID-19 hospitalisation, the risk of severe COVID-19 seems to be extremely low in general adolescents. Therefore, administration of additional doses to the general population of adolescents may not be warranted at this stage of the pandemic. In contrast, individuals with a high risk for severe COVID-19 should be prioritised for vaccination.