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

BackgroundVaccination 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 MethodsThe 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. ResultsMost 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. ConclusionsIn 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.

Age and product dependent vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adults in Norway: a national cohort study, July - November 2021. (preprint)

Background: COVID-19 vaccines have been crucial in the pandemic response and understanding changes in vaccines effectiveness is essential to guide vaccine policies. Though the Delta variant is no longer dominant, understanding vaccines effectiveness properties will provide essential knowledge to comprehend the development of the pandemic and estimate potential changes over time. Methods: In this population-based cohort study, we estimated vaccine effectiveness against SARS-CoV-2 infections, hospitalisations, intensive care admissions, and death using Cox proportional hazard models, across different vaccine product regimens and age groups, between 15 July and 31 November 2021 (Delta variant period). Vaccine status is included as a time-varying covariate and all models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the entire adult Norwegian population were collated from the National Preparedness Register for COVID-19 (Beredt C19). Results: The overall adjusted vaccine effectiveness against infection decreased from 81.3% (confidence interval (CI): 80.7 to 81.9) in the first two to nine weeks after receiving a second dose to 8.6% (CI:4.0 to 13.1) after more than 33 weeks, compared to 98.6% (CI: 97.5 to 99.2) and 66.6% (CI: 57.9 to 73.6) against hospitalisation respectively. After the third dose (booster), the effectiveness was 75.9% (CI: 73.4 to 78.1) against infection and 95.0% (CI: 92.6 to 96.6) against hospitalisation. Spikevax or a combination of mRNA products provided the highest protection, but the vaccine effectiveness decreased with time since vaccination for all vaccine regimens. Conclusions: Even though the vaccine effectiveness against infection wanes over time, all vaccine regimens remained effective against hospitalisation after the second vaccine dose. For all vaccine regimens, a booster facilitated recovery of effectiveness. The results from this support the use of heterologous schedules, increasing flexibility in vaccination policy.

Vaccine effectiveness with BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine against reported SARS-CoV-2 Delta and Omicron infection among adolescents, Norway, August 2021 to January 2022 (preprint)

Background: COVID-19 vaccination was recommended for adolescents in Norway since August 2021. In this population-based cohort study, we estimated the BNT162b2 vaccine effectiveness against any PCR-confirmed (symptomatic or not) SARS-CoV-2 infections caused by the Delta and Omicron variant among adolescents (12-17-years-old) in Norway from August 2021 to January 2022. Methods: Using Cox proportional hazard models, we estimated the BNT162b2 vaccine effectiveness against any Delta and Omicron infections. Vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data were obtained from the National Preparedness registry for COVID-19, which contains individual-level data from national health and administrative registries. Findings: Vaccine effectiveness against Delta infection peaked at 68% (95%CI: 64-71%) and 62% (95%CI: 57-66%) in days 21-48 after the first dose among 12-15-year-olds and 16-17-year-olds respectively. Among 16-17-year-olds that received two doses, vaccine effectiveness peaked at 93% (95%CI: 90-95%) in days 35-62 and declined to 84% (95%CI: 76-89%) in 63 days or more after the second dose. For both age-groups, we found no protection against Omicron infection after receiving one dose. Among 16-17-year-olds, vaccine effectiveness against Omicron infection peaked at 53% (95%CI: 43-62%) in 7-34 days after the second dose and decreased to 23% (95%CI: 3-40%) in 63 days or more after vaccination. Vaccine effectiveness decreased with time since vaccination for both variants, but waning was observed to occur faster for Omicron. Interpretation: Our results suggest reduced protection from BNT162b2 vaccination against any SARS-CoV-2 infection caused by the Omicron variant compared to the Delta. In addition, waning immunity was observed to occur faster for Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance. Funding: No funding was received.