In a recent study published in The New England Journal of Medicine, researchers evaluated Pfizer-BioNTech’s BNT162b2 messenger ribonucleic acid (mRNA) vaccine effectiveness (VE) against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infections among the pediatric and adolescent population of Qatar.
Five coronavirus disease 2019 (COVID-19) waves have occurred in Qatar, sequentially dominated by the SARS-CoV-2 index strain, the Alpha variant of concern (VOC), the Beta VOC, Omicron BA.1 and Omicron BA.2 sub-VOCs, and Omicron BA.4/5 sub-VOCs, apart from a long-lasting low-incidence Delta VOC-dominated phase. BNT162b2 vaccinations against COVID-19 have been approved for children aged between five years and 11 years and adolescent individuals between 12 years and 17 years, but the vaccine doses differ for the two groups.
About the study
In the present study, researchers assessed the real-world BNT162b2 VE against COVID-19 among the pediatric and adolescent population of Qatar. The study was a subset of a national-level study.
The team analyzed data obtained from the federated national-level databases for SARS-CoV-2 testing in laboratories, vaccinations, hospitalizations, and deaths, including demographic data and reports of PCR (polymerase chain reaction) and RAT (rapid antigen tests) conducted from 5 January 2022 onwards, without any missing data since COVID-19 onset.
For comparing COVID-19 incidence among vaccinated and unvaccinated individuals, three retrospective cohort-type studies were conducted, of which one assessed data of five to 11-year-old children post-Omicron dominance, and the remaining two assessed data of 12-year to 17-year-old adolescent individuals before and after Omicron prevalence. Children doubly vaccinated between 3 February 2022 and 12 July 2022 comprised the vaccinated cohort of the pediatric Omicron study.
Adolescents doubly vaccinated between 1 February 2021, and 30 November 2021, comprised the vaccinated cohort of the adolescent pre-Omicrons study, and those doubly vaccinated between 1 February 2021 and 12 July 2022 comprised the vaccinated cohort of the adolescent Omicron study. Primary BNT162b2 vaccination doses were 10μg and 30μg for children and adolescents, respectively.
Vaccinees were matched to non-vaccinees based on age, sex, nationality, and coexisting medical conditions. In addition, vaccinated individuals were matched based on the month of D2 (second dose) administration, and controls were matched based on the month of a negative result. Individuals with prior COVID-19 history were excluded from the analysis. The included individuals were followed up until a SARS-CoV-2-positive result (by RAT or PCR irrespective of symptoms of COVID-19), booster dose administrations, initial vaccination among controls, mortality, or study termination.
Cox proportional hazards regression modeling was used for the analysis. For informing SARS-CoV-2 infection response in the country, five percent of SARS-CoV-2-positive cases were targeted for genomic sequencing, and a greater proportion was targeted for genotyping using multiplexed real-time RT-PCR (reverse transcription PCR) screening for SARS-CoV-2 VOCs.
The matched cohort of the pediatric Omicron study comprised 18,728 individuals. In the follow-up period, 184 and 248 SARS-CoV-2 infections were documented among the vaccinees and controls, respectively; however, none of them had severe COVID-19 outcomes. COVID-19 incidence coincided with BA.1, BA.2, and BA.4/5 prevalence. The cumulative COVID-19 incidence rates after a follow-up of 110 days were two percent in both cohorts, with a hazard ratio (HR) value of 0.7.
The adolescent pre-Omicron study comprised 23,317 matched adolescent individuals. 23,317 adolescents, of which 67 vaccinees and 523 controls developed SARS-CoV-2 infections; however, none of them were severe. The cases coincided with Alpha, Beta, and particularly Delta predominance. The cumulative COVID-19 incidence rates after following up for 135 days were 0.8% and four percent for the vaccinees and controls, respectively, with an overall HR for infection of 0.1.
The adolescent Omicron study comprised 17,903 adolescent individuals, of which 2,520 vaccinees and 3,337 controls developed SARS-CoV-2 infections, and one individual in each cohort experienced COVID-19 severity. COVID-19 incidence initially coincided with Omicron BA.1 and Omicron BA.2 predominance and, subsequently, with that of Omicron BA.1, Omicron BA.2, and Omicron BA.4/5. The cumulative COVID-19 incidence rates after following up for 195 days were 16% and 21% for the vaccinees and controls, respectively, with an overall HR of 0.7.
Among the pediatric group, the estimated VE for primary BNT162b2 vaccinations against Omicron infections was 26%. The highest VE values (50%) were obtained immediately after D2 but dropped rapidly and were almost nil after three months. VE estimates were 46% and 17% among individuals aged five to seven years and those aged eight to 11 years, respectively.
Among adolescent individuals, a 31% VE was observed for primary BNT162b2 vaccinations against Omicron infections, although several adolescents had received vaccinations previously. VE reduced with time since D2 was administered. VE estimates of 36% and 21% were obtained for 12- to 14-year-old adolescents and those aged between 15 and 17 years, respectively.
In the pre-Omicron prevalence study, the VE of primary BNT162b2 vaccinations against COVID-19 among adolescent individuals was 88%, which reduced gradually after D2 was administered. Similar results were obtained in the sensitivity analysis after adjusting for testing frequency differences among the two groups of the three randomized target trials.
Overall, the study findings showed that BNT162b2 vaccinations were associated with modest and swiftly waning immune protection against Omicron infections among children. In contrast, the association was stronger with more durable immune protection among adolescents.