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Background There have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used. Methods In this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from the Norwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group. Results Between December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 [95% CI: 0.24–0.31]). Similar results were obtained in analyses stratified by use of health services and age group. Conclusion We found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality. publishedVersion

BackgroundCOVID-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.MethodsUsing 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.FindingsVaccine 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.InterpretationOur 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.FundingNo funding was received.Research in contextEvidence before this studyBNT162b2 (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 studyThe 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 evidenceBased 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.