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Severe acute respiratory infections (SARI) are estimated to be the cause of death in about 19% of all children younger than 5 years globally. The outbreak of coronaviral disease (COVID-19) caused by SARS-CoV-2, increased considerably the burden of SARI worldwide. We used data from a vaccine effectiveness study to identify the factors associated with SARS CoV-2 infection among hospitalized SARI patients. We recruited SARI patients at 3 hospitals in Serbia from 7 April 2022-1 May 2023. We collected demographic and clinical data from patients using a structured questionnaire, and all SARI patients were tested for SARS-CoV-2 by RT-PCR. We conducted an unmatched test negative case-control study. SARS-CoV-2 infected SARI patients were considered cases, while SARS CoV-2 negative SARI patients were controls. We conducted bivariate and multivariable logistic regression analysis in order to identify variables associated with SARS-CoV-2 infection. We included 110 SARI patients: 74 were cases and 36 controls. We identified 5 factors associated with SARS-CoV-2 positivity, age (OR = 1.04; 95% CI = 1.01-1.07), having received primary COVID-19 vaccine series (OR = 0.28; 95% CI = 0.09-0.88), current smoking (OR = 8.64; 95% CI = 2.43-30.72), previous SARS CoV-2 infection (OR = 3.48; 95% CI = 1.50-8.11) and number of days before seeking medical help (OR = 0.81; 95% CI = 0.64-1.02). In Serbia during a period of Omicron circulation, we found that older age, unvaccinated, hospitalized SARI patients, previously infected with SARS CoV-2 virus and those who smoked, were more likely to be SARS-CoV-2-positive; these patient populations should be prioritized for COVID vaccination.