Obesity and COVID-19: Pathophysiological Insights and Pulmonary Complications in a Retrospective Cohort Study

<b>Background/Objectives</b>: Obesity is a major modifier of COVID-19 outcomes, contributing to increased disease severity and complications. This study aimed to assess the impact of obesity on clinical severity, pulmonary involvement, and in-hospital mortality among COVID-19 patients and to identify independent predictors of severe disease. <b>Methods:</b> We conducted a retrospective cohort study of 3005 hospitalized adults with RT-PCR-confirmed COVID-19 between 1 January 2020 and 1 March 2023. Patients were stratified by obesity status (body mass index (BMI) ≥ 30 kg/m²). Clinical, comorbidity, imaging, and laboratory data, as well as vaccination status (vaccinated or unvaccinated), were collected. Multivariate regression and gradient boosting models were used to identify predictors of severe outcomes. Effect estimates are expressed as relative risks (RRs) with 95% confidence intervals (CIs). <b>Results:</b> Obese patients (<i>n</i> = 894) showed significantly higher rates of severe COVID-19 (31.7% vs. 22.4%, <i>p</i> < 0.001) and more extensive lung damage (>50% involvement: 27.9% vs. 22.0%, <i>p</i> < 0.001), with lower admission SpO₂ (92.1 ± 4.0% vs. 94.2 ± 3.2%, <i>p</i> < 0.001). Hypoxemia (SpO₂ < 90%) was more frequent in obese individuals. The relative risk (RR) for severe disease was 1.41 (95% CI 1.25-1.60), and for >50% lung involvement, it was 1.27 (95% CI 1.11-1.45). Age > 65 years was the strongest predictor of mortality, particularly in non-obese patients. Gradient boosting models outperformed logistic regression (AUC = 0.92 vs. 0.87). <b>Conclusions:</b> Obesity independently predicts severe COVID-19 and pulmonary impairment. These findings support obesity-based risk stratification for clinical management and public health interventions.