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Objective: To provide a comprehensive overview of the epidemiologic characteristics, outcomes, and risk factors of COVID-19-related deaths in children and adolescents in Brazil., Study Design: We conducted a population-based, retrospective cohort study that included all patients aged <18 years with laboratory-confirmed, symptomatic SARS-CoV-2 infection as registered in official Brazilian national surveillance systems for COVID-19 between February 2020 and February 2023. The primary outcome was COVID-19-related deaths. Odds ratios (ORs) of risk factors associated with death were estimated using multivariable logistic regression., Results: Over a 3-year period, 2 855 704 pediatric patients with symptomatic SARS-CoV-2 infection were registered in Brazil. Of these, 59 179 (2.1%) were hospitalized, 13 844 (0.48%) were admitted to the intensive care unit, and 4943 (0.17%) received mechanical ventilation. A total of 4740 (0.17%) patients had fatal outcomes. The case fatality rate increased to 7.9% among patients who required hospitalization; 2102 (44.3%) patients who died did not receive advanced critical support. Notably, 2 (65%, 95% CI 58-71) or 3 doses (86%, 95% CI 81-89) of the vaccine provided strong protection against death. The following adjusted covariates were significantly associated with increased odds of death: age (0-4 and 11-17 years), ethnicity (Brown and Indigenous), region (Northeast or North), dyspnea, nosocomial infection, and comorbidities. Conversely, living in the South or Central-West regions, admission in the later period of the pandemic, and receiving a vaccine were all associated with protection against death., Conclusions: Our findings suggest that a complex interplay between individual factors and social inequities has shaped the impact of COVID-19 on Brazilian children and adolescents., Competing Interests: Declaration of Competing Interest This study was supported by the CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FAPEMIG (Fundação de Amparo a Pesquisa do Estado de Minas Gerais). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)