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Our study population consisted of all children and adolescents, with laboratory-confirmed SARS-Co-V-2 infection, hospitalised from February 2020 through February 2022, among residents of the Tel Aviv (TA) District, Israel. There were 491 children and adolescents hospitalised with Sars-CoV-2 infection. Among them, 281 (57%) admitted with coronavirus disease 2019 (COVID-19) as the primary cause of admission (rate of 39 per 100 000). Among all children and adolescents in the TA District, the highest hospitalisation rates were observed among infants and children below the age of 4 years (rate of 311 per 100 000 population). Severe disease was observed mostly among children with multiple underlying medical conditions. Admission rates were also elevated among residents of the ultra-orthodox community (rate ratio (RR) compared to the rest of the district; 95% confidence interval (CI) 2.38-3.82). Admission rates with COVID-19 as primary cause of admission were higher during Omicron compared to Delta predominance period (RR 1.7; 95% CI 1.22-2.32). Targeted social and public health policies should be put in place when rates of disease start to increase, such as encouraging vaccine uptake for eligible children and social distancing when necessary, taking into account already existing social and learning gaps, in order to reduce the burden of disease.