BackgroundWe aimed to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection, its effect on COVID-19 presentation, and post-vaccination symptoms in children and young people (CYP) in the UK during periods of Delta and Omicron variant predominance. MethodsIn this prospective longitudinal cohort study, we analysed data from 115,775 CYP aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2, and described the illness profile of CYP with post-vaccination SARS- CoV-2 infection, compared to unvaccinated CYP, and post-vaccination side-effects. FindingsBetween August 5, 2021 and February 14, 2022, 25,971 UK CYP aged 12-17 years received one dose of BNT162b2 vaccine. Vaccination reduced (proxy-reported) infection risk (-80{middle dot}4% and -53{middle dot}7% at 14-30 days with Delta and Omicron variants respectively, and -61{middle dot}5% and -63{middle dot}7% after 61-90 days). The probability of remaining infection-free diverged soon after vaccination, and was greater in CYP with prior SARS-CoV-2 infection. Vaccinated CYP who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CYP; during the Omicron period this was only evident in children aged 12-15 years. Overall disease profile was similar in both vaccinated and unvaccinated CYP. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved quickly. InterpretationOne dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CYP aged 12-17 years. Vaccine protection varied for SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination was generally milder, although unvaccinated CYP also had generally mild disease. Overall, vaccination was well-tolerated. FundingUK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimers Society, and ZOE Limited. Research in context Evidence before this studyWe searched PubMed database for peer-reviewed articles and medRxiv for preprint papers, published between January 1, 2021 and February 15, 2022 using keywords ("SARS-CoV-2" OR "COVID-19") AND (child* OR p?ediatric* OR teenager*) AND ("vaccin*" OR "immunization campaign") AND ("efficacy" OR "effectiveness" OR "symptoms") AND ("delta" or "omicron" OR "B.1.617.2" OR "B.1.1.529"). The PubMed search retrieved 36 studies, of which fewer than 30% specifically investigated individuals <18 years. Eleven studies explored SARS-CoV-2 viral transmission seroprevalence in children (n=4), including age-dependency of susceptibility to SARS-CoV-2 infection (n=1), SARS-CoV-2 transmission in schools (n=5), and the effect of school closure on viral transmission (n=1). Eighteen documents reported clinical aspects, including manifestation of infection (n=13), symptomatology, disease duration, and severity in children. Other studies estimated emergency department visits, hospitalization, need for intensive care, and/or deaths in children (n=4), and explored prognostic factors (n=1). Thirteen studies explored vaccination-related aspects, including vaccination of children within specific paediatric co-morbidity groups (e.g., children with Down syndrome, inflammatory bowel disease, and cancer survivors, n=4), mRNA vaccine efficacy in children and adolescents from the general population (n=7), and the relation between vaccination and severity of disease and hospitalization cases (n=2). Four clinical trials were conducted using mRNA vaccines in minors, also exploring side effects. Sixty percent of children were found to have side effects after BNT162b2 vaccination, and especially after the second dose; however, most symptoms were mild and transient apart from rare uncomplicated skin ulcers. Two studies focused on severe adverse effects and safety of SARS-CoV-2 vaccines in children, reporting on myocarditis episodes and two cases of Guillain-Barre syndrome. All other studies were beyond the scope of our research. Added value of this studyWe assessed multiple components of the UK vaccination campaign in a cohort of children and young people (CYP) aged 12-17 years drawn from a large UK community-based citizen-science study, who received a first dose of BNT162b2 vaccine. We describe a variant-dependent protective effect of the first dose against both Delta and Omicron, with additional protective effect of pre-vaccination SARS- CoV-2 infection on post-vaccination re-infection. We compare the illness profile in CYP infected post-vaccination with that of unvaccinated CYP, demonstrating overall milder disease with fewer symptoms for vaccinated CYP. We describe local and systemic side-effects during the first week following first-dose vaccination, confirming that local symptoms are common, systemic symptoms uncommon, and both usually transient. Implications of all the available evidenceOur data confirm that first dose BNT162b2 vaccination in CYP reduces risk of infection by SARS-CoV-2 variants, with generally local and brief side-effects. If infected after vaccination, COVID-19 is milder, if manifest at all. The study aims to contribute quantitative evidence to the risk-benefit evaluation of vaccination in CYP to inform discussion regarding rationale for their vaccination and the designing of national immunisation campaigns for this age group; and applies citizen-science approaches in the conduct of epidemiological surveillance and data collection in the UK community. Importantly, this study was conducted during Delta and Omicron predominance in UK; specificity of vaccine efficacy to variants is also illustrated; and results may not be generalizable to future SARS-CoV-2 strains.