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Objective: To estimate the effectiveness of a two dose vaccine schedule (mRNA-1273, BNT162b2, and BBIBP-CorV) against SARS-CoV-2 infection and covid-19 related death and short term waning of immunity in children (3-11 years old) and adolescents (12-17 years old) during periods of delta and omicron variant predominance in Argentina., Design: Test negative, case-control study., Setting: Database of the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina., Participants: 844 460 c hildren and adolescents without previous SARS-CoV-2 infection eligible to receive primary vaccination schedule who were tested for SARS-CoV-2 by polymerase chain reaction or rapid antigen test from September 2021 to April 2022. After matching with their corresponding controls, 139 321 (60.3%) of 231 181 cases remained for analysis., Exposures: Two dose mRNA-1273, BNT162b2, and BBIBP-CorV vaccination schedule., Main Outcome Measures: SARS-CoV-2 infection and covid-19 related death. Conditional logistic regression was used to estimate the odds of SARS-CoV-2 infection among two dose vaccinated and unvaccinated participants. Vaccine effectiveness was estimated as (1-odds ratio)×100%., Results: Estimated vaccine effectiveness against SARS-CoV-2 infection was 61.2% (95% confidence interval 56.4% to 65.5%) in children and 66.8% (63.9% to 69.5%) in adolescents during the delta dominant period and 15.9% (13.2% to 18.6%) and 26.0% (23.2% to 28.8%), respectively, when omicron was dominant. Vaccine effectiveness declined over time, especially during the omicron period, from 37.6% (34.2% to 40.8%) at 15-30 days after vaccination to 2.0% (1.8% to 5.6%) after ≥60 days in children and from 55.8% (52.4% to 59.0%) to 12.4% (8.6% to 16.1%) in adolescents.Vaccine effectiveness against death related to SARS-CoV-2 infection during omicron predominance was 66.9% (6.4% to 89.8%) in children and 97.6% (81.0% to 99.7%) in adolescents., Conclusions: Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time., Trial Registration: National Registry of Health Research IS003720., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; JMC and CV were involved in the decision making process of the vaccination campaign in Argentina; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)