Djuric, Marko (56467826000)Marko (56467826000)DjuricNenadic, Irina (57248341000)Irina (57248341000)NenadicRadisavljevic, Nina (57201418152)Nina (57201418152)RadisavljevicTodorovic, Dusan (57202724895)Dusan (57202724895)TodorovicDimic, Nemanja (57460624900)Nemanja (57460624900)DimicBobos, Marina (59782431600)Marina (59782431600)BobosBojic, Suzana (55965837500)Suzana (55965837500)BojicSavic, Predrag (57272197000)Predrag (57272197000)SavicTurnic, Tamara Nikolic (58237706100)Tamara Nikolic (58237706100)TurnicStevanovic, Predrag (24315050600)Predrag (24315050600)StevanovicDjukic, Vladimir (57210262273)Vladimir (57210262273)Djukic2025-06-122025-06-122025https://doi.org/10.3390/healthcare13091041https://www.scopus.com/inward/record.uri?eid=2-s2.0-105005116185&doi=10.3390%2fhealthcare13091041&partnerID=40&md5=a52bcc57ce63959ddb972299e0eb554fhttps://remedy.med.bg.ac.rs/handle/123456789/488Background: The COVID-19 pandemic revealed an unexpected pattern known as the “smoker’s paradox”, with lower rates of severe disease among smokers compared to non-smokers, highlighting the need for the specific investigation of disease progression in non-smoking populations. Objective: To identify early mortality predictors in non-smoking patients with severe COVID-19 through the evaluation of clinical, laboratory, and oxygenation parameters. Methods: This retrospective observational cohort study included 59 non-smokers hospitalized with COVID-19 between November and December 2020. Clinical parameters, laboratory findings, and respiratory support requirements were analyzed on Days 1 and 7 of hospitalization. ROC curves were constructed to assess the predictive value of the parameters. Results: The overall mortality rate was 54.2%. The seventh-day SOFA score showed the strongest predictive value (AUC = 0.902, p = 0.004), followed by pCO2 (AUC = 0.853, p = 0.012). Significant differences between survivors and non-survivors were observed in acid–base parameters, oxygenation indices, and hematological markers. Mortality rates varied significantly with ventilation type: 84.6% for IMV and 50% for NIMV, with no deaths in HFNC patients. Conclusions: Multiple parameters measured on Day 7 of hospitalization demonstrate significant predictive value for mortality in non-smoking COVID-19 patients, with the SOFA score being the strongest predictor. The type of respiratory support significantly influences outcomes, suggesting the importance of careful ventilation strategy selection. © 2025 by the authors.COVID-19mortalitynon-smokerpredictorsscores