ABSTRACT
Background: The two-dose BNT162b2 (Pfizer-BioNTech) vaccine has demonstrated high efficacy against COVID-19 disease in clinical trials of children and young people (CYP). Consequently, we investigated the uptake, safety, effectiveness and waning of the protective effect of the BNT162b2 against symptomatic COVID-19 in CYP aged 12-17 years in Scotland. Methods: The analysis of the vaccine uptake was based on information from the Turas Vaccination Management Tool, inclusive of Mar 1, 2022. Vaccine safety was evaluated using national data on hospital admissions and General Practice (GP) consultations, through a self-controlled case series (SCCS) design, investigating 17 health outcomes of interest. Vaccine effectiveness (VE) against symptomatic COVID-19 disease for Delta and Omicron variants was estimated using a test-negative design (TND) and S-gene status in a prospective cohort study using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. The waning of the VE following each dose of BNT162b2 was assessed using a matching process followed by conditional logistic regression. Findings: Between Aug 6, 2021 and Mar 1, 2022, 75.9% of the 112,609 CYP aged 16-17 years received the first and 49.0% the second COVID-19 vaccine dose. Among 237,681 CYP aged 12-15 years, the uptake was 64.5% and 37.2%, respectively. For 12-17-year-olds, BNT162b2 showed an excellent safety record, with no increase in hospital stays following vaccination for any of the 17 investigated health outcomes. In the 16-17-year-old group, VE against symptomatic COVID-19 during the Delta period was 64.2% (95% confidence interval [CI] 59.2-68.5) at 2-5 weeks after the first dose and 95.6% (77.0-99.1) at 2-5 weeks after the second dose. The respective VEs against symptomatic COVID-19 in the Omicron period were 22.8% (95% CI -6.4-44.0) and 65.5% (95% CI 56.0-73.0). In children aged 12-15 years, VE against symptomatic COVID-19 during the Delta period was 65.4% (95% CI 61.5-68.8) at 2-5 weeks after the first dose, with no observed cases at 2-5 weeks after the second dose. The corresponding VE against symptomatic COVID-19 during the Omicron period were 30.2% (95% CI 18.4-40.3) and 81.2% (95% CI 77.7-84.2). The waning of the protective effect against the symptomatic disease began after five weeks post-first and post-second dose. Interpretation: During the study period, uptake of BNT162b2 in Scotland has covered more than two-thirds of CYP aged 12-17 years with the first dose and about 40% with the second dose. We found no increased likelihood of admission to hospital with a range of health outcomes in the period after vaccination. Vaccination with both doses was associated with a substantial reduction in the risk of COVID-19 symptomatic disease during both the Delta and Omicron periods, but this protection began to wane after five weeks. Funding: UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Chief Scientist's Office of the Scottish Government; Health Data Research UK; National Core Studies - Data and Connectivity.
ABSTRACT
BACKGROUND: Little is known about vaccine effectiveness over time among adolescents, especially against the SARS-CoV-2 omicron (B.1.1.529) variant. This study assessed the associations between time since two-dose vaccination with BNT162b2 and the occurrence of symptomatic SARS-CoV-2 infection and severe COVID-19 among adolescents in Brazil and Scotland. METHODS: We did test-negative, case-control studies in adolescents aged 12-17 years with COVID-19-related symptoms in Brazil and Scotland. We linked records of SARS-CoV-2 RT-PCR and antigen tests to national vaccination and clinical records. We excluded tests from individuals who did not have symptoms, were vaccinated before the start of the national vaccination programme, received vaccines other than BNT162b2 or a SARS-CoV-2 booster dose of any kind, or had an interval between their first and second dose of fewer than 21 days. Additionally, we excluded negative SARS-CoV-2 tests recorded within 14 days of a previous negative test, negative tests recorded within 7 days after a positive test, any test done within 90 days after a positive test, and tests with missing sex and location information. Cases (SARS-CoV-2 test-positive adolescents) and controls (test-negative adolescents) were drawn from a sample of individuals in whom tests were collected within 10 days of symptom onset. We estimated the adjusted odds ratio and vaccine effectiveness against symptomatic COVID-19 for both countries and against severe COVID-19 (hospitalisation or death) for Brazil across fortnightly periods. FINDINGS: We analysed 503 776 tests from 2 948 538 adolescents in Brazil between Sept 2, 2021, and April 19, 2022, and 127 168 tests from 404 673 adolescents in Scotland between Aug 6, 2021, and April 19, 2022. Vaccine effectiveness peaked at 14-27 days after the second dose in both countries during both waves, and was significantly lower against symptomatic infection during the omicron-dominant period in Brazil (64·7% [95% CI 63·0-66·3]) and in Scotland (82·6% [80·6-84·5]), than it was in the delta-dominant period (80·7% [95% CI 77·8-83·3] in Brazil and 92·8% [85·7-96·4] in Scotland). Vaccine efficacy started to decline from 27 days after the second dose for both countries, reducing to 5·9% (95% CI 2·2-9·4) in Brazil and 50·6% (42·7-57·4) in Scotland at 98 days or more during the omicron-dominant period. In Brazil, protection against severe disease remained above 80% from 28 days after the second dose and was 82·7% (95% CI 68·8-90·4) at 98 days or more after receiving the second dose. INTERPRETATION: We found waning vaccine protection of BNT162b2 against symptomatic COVID-19 infection among adolescents in Brazil and Scotland from 27 days after the second dose. However, protection against severe COVID-19 outcomes remained high at 98 days or more after the second dose in the omicron-dominant period. Booster doses for adolescents need to be considered. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Health Data Research UK BREATHE Hub, Fiocruz, Fazer o Bem Faz Bem programme, Brazilian National Research Council, and Wellcome Trust. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.