Adverse Events Following SARS-CoV-2 mRNA Vaccination in Adolescents: A Norwegian Nationwide Register-Based Study

Background Vaccination of older adolescents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the spring of 2021 and continued with younger adolescents throughout the summer and fall. We assessed risks of adverse events following immunization (AEFI) in adolescents aged 12–19 years following SARS-CoV-2 vaccination with a messenger RNA (mRNA) vaccine in Norway. Materials and Methods The study sample included 496,432 adolescents born in 2002–2009, residing in Norway, and unvaccinated against SARS-CoV-2 at the beginning of the age-specific waves of vaccination in 2021. The exposures under study were first- and second-dose SARS-CoV-2 mRNA vaccinations vs. no dose. We applied Poisson regression and self-controlled case series (SCCS) analysis to estimate incidence rate ratios (IRRs) of 17 preselected outcomes, with associated 95% confidence intervals (CIs), between vaccinated and unvaccinated subjects using predefined post-vaccination risk windows. Results Most outcome-specific numbers of cases were low. There were no statistically significant associations between first-dose vaccination and any of the outcomes. In the main Poisson regression, second-dose vaccination was associated with increased risks of anaphylactic reaction (adjusted IRR [aIRR]: 10.05; 95% CI: 1.22–82.74), lymphadenopathy (aIRR: 2.33; 95% CI: 1.46–3.72), and myocarditis and pericarditis (aIRR: 5.27; 95% CI: 1.98–14.05). We also observed increased incidence of acute appendicitis outside the 14-day risk window. When expanding the risk window to 42 days in a post-hoc analysis, there was increased incidence of acute appendicitis following both first-dose vaccination (aIRR: 1.39; 95% CI: 1.09–1.78) and second-dose vaccination (aIRR: 1.43; 95% CI: 1.07–1.91). Results of the SCCS analysis were similar to the Poisson regression. Conclusions In general, potential AEFI were rare among adolescents. We found increased risks of anaphylactic reaction, lymphadenopathy, and myocarditis and pericarditis following second-dose vaccination. There were also indications of increased acute appendicitis risk when applying longer risk windows. ### Competing Interest Statement OEK and PLDR reports participation in research projects funded by Novo Nordisk, LEO Pharma and Bristol-Myers Squibb, all regulator-mandated phase IV studies, all with funds paid to their institution (no personal fees) and with no relation to the work reported in this paper. HLG reports previous participation in research projects and clinical trials funded by Novo Nordisk, GSK, AstraZeneca, and Boehringer-Ingelheim, all related to diabetes and paid to her previous institution Oslo University Hospital (no personal fees). She has received a lecture fee from Sanofi-Aventis (2018). All other authors report no conflict of interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The emergency preparedness register Beredt C19 was established by the Norwegian Institute of Public Health according to the Health Preparedness Act paragraph 2-4, and the study was approved by the Regional Committee for Medical and Health Research Ethics South-East Norway (REK South East A, ref 122745). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Due to the nature of the Emergency register, the authors do not have permission to share individual-level data. Data are only accessible to authorized researchers pending ethical approval and successful application to [www.helsedata.no][1]. [1]: http://www.helsedata.no