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

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. Evidence before this study BNT162b2 (Comirnaty, Pfizer-BioNTech) and mRNA-1273 (Spikevax, Moderna) vaccines have been approved for use in adolescents, based on results from randomized placebo-controlled trials demonstrating comparable immunogenicity and safety profile as in young adults. In addition, observational studies from Israel, the USA and England have reported high protection of BNT162b2 vaccines against SARS-CoV-2 Delta infection among adolescents. These studies also reported decrease in effectiveness with time since last vaccine dose. Evidence on the effect of an extended interval between doses, longer time since vaccination and the effect against different variants is limited. When we first planned this study in early February 2022, no data were available regarding vaccine effectiveness against SARS-CoV-2 Omicron infection among adolescents. To our knowledge when we completed this study and before submitting this article, only one study from England reported results in a preprint on vaccine effectiveness against symptomatic SARS-CoV-2 Omicron infection among adolescents. We searched for studies that evaluated vaccine efficacy or effectiveness after vaccination of adolescents during 2021-2022 in PubMed, medRxiv, bioRxiv, SSRN. We searched for studies with several variations of the primary key search terms “COVID-19”, “SARS-CoV-2”, and “vaccine” (including names of specific vaccines, as BNT162b2), “vaccine effectiveness”, “adolescents”, “children”. Added value of this study The rapid increase in the incidence of SARS-CoV-2 infection caused by the Omicron variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines in adults but also adolescents. In this population-based cohort study, we showed that the vaccine effectiveness against Omicron is lower than against Delta infections among adolescents, including symptomatic and asymptomatic infections. We should note that evidence suggests higher rates of asymptomatic carriage for Omicron than other variants of concern. Vaccine effectiveness that includes asymptomatic cases, as in the study from England, is expected to be lower than when including symptomatic cases only. We found that one and two doses of BNT162b2 among adolescents protected well against Delta. Vaccination provided high protection against Delta infections (>91%) among Norwegian 16-17-year-olds 7-62 days after the second dose. We found no protection against Omicron SARS-CoV-2 infection after one vaccine dose, and moderate effectiveness after two doses (peaked at 53%) among the 16-17-year-olds. Moreover, waning immunity was observed to occur faster for Omicron. Implications of all the available evidence Based on the available evidence, the vaccine effectiveness among adolescents is similar to that reported among adults, also with an extended period of 8-12 weeks between doses which was used in Norway. Protection is significantly lower against Omicron than Delta infections and immunity wanes faster against Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance. Policies should take into account the impact of vaccination campaigns among adolescents and their primary objective. Vaccine effectiveness should be re-evaluated when other variants appear as they might have different outcomes as shown between Delta and Omicron infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research did not receive any specific grant from funding agencies in the public, commercial, or not‒for‒profit sectors. The study was performed as part of routine work at the Norwegian Institute of Public Health. ### 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: Ethical approval was granted by Regional Committees for Medical and Health Research Ethics (REC) Southeast (reference number 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The dataset analysed in the study contains individual‒level linked data from various central health registries, national clinical registries, and other national administrative registries in Norway. The researchers had access to the data through the national emergency preparedness registry for COVID‒19 (Beredt C19), housed at the Norwegian Institute of Public Health (NIPH). In Beredt C19, only fully anonymised data (i.e. data that are neither directly nor potentially indirectly identifiable) are permitted to be shared publicly. Legal restrictions therefore prevent the researchers from publicly sharing the dataset used in the NH study that would enable others to replicate the study findings. However, external researchers are freely able to request access to linked data from the same registries from outside the structure of Beredt C19, as per normal procedure for conducting health research on registry data in Norway. Further information on Beredt C19, including contact information for the Beredt C19 project manager, and information on access to data from each individual data source, is available at https://www.fhi.no/en/id/infectious-diseases/coronavirus/emergency-preparedness-register-for-covid-19/.