(1) Background: Our study aims to investigate the utility of inflammatory factors as prognostic indicators for disease severity and mortality in COVID-19 patients admitted to the Intensive Care Unit (ICU) Department of Pelican Clinical Hospital Oradea Romania. While elevated white blood cell (WBC) levels are associated with COVID-19 severity and mortality, they may not effectively predict the risk of death; (2) Methods: In our ICU department, we conducted assessments on the 10th and 14th days of COVID-19 patients’ hospitalization, measuring the following markers: C-reactive protein (CRP) levels, procalcitonin (PCT) levels, granulocytes/lymphocytes (G/L) ratios, ferritin levels, age, and obesity status. We included a total of 209 eligible COVID-19 patients in the final analysis. Our goal was to identify biomarkers that could quickly identify high-risk patients with a potential for disease progression and mortality; (3) Results: Our study (a retrospective, single-center observational cohort study) demonstrated statistically significant differences in predicting mortality and disease severity based on G/L ratio (p < 0.0001), PCT (p < 0.0002), CRP (p < 0.0001), ferritin (p < 0.0001), age (p < 0.0001), and obesity (p < 0.0001); (4) Conclusions: Having a G/L ratio exceeding 20 units, along with elevated levels of PCR, PCT, and ferritin in older and obese patients on the 3rd day of ICU admission, represents significant risk factors for in-hospital mortality in severe COVID-19 patients.
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