Predictors of Severe Outcomes in COVID-19: Evidence from Real-World Multicenter Retrospective Study (2020–2024)

<b>Background/Objectives</b>: This study analyzed demographic, clinical, laboratory, and outcome data from patients hospitalized with Coronavirus disease 2019 in eastern Poland between March 2020 and December 2024. This study aimed to assess sex-related differences in clinical features, treatments, and outcomes, and to identify predictors of mortality and mechanical ventilation in hospitalized patients. <b>Methods</b>: A retrospective cohort of 2811 adults hospitalized across four infectious disease centers was examined. Data included demographics, comorbidities, symptoms, laboratory findings, treatments, and clinical outcomes. Multivariable logistic regression was performed to identify predictors of mortality and mechanical ventilation. <b>Results</b>: The cohort comprised 1398 females and 1413 males. Women were older (median 67.5 vs. 63 years, <i>p</i> < 0.0001) and had a higher burden of comorbidities, while men presented with more severe baseline respiratory status and higher inflammatory markers. Oxygen therapy was required more frequently in men (60% vs. 49.9%, <i>p</i> < 0.0001). Overall mortality was 8.9% and did not differ significantly by sex, although men aged 60-79 years had higher mortality than women (11.2% vs. 7.7%, <i>p</i> = 0.0422). Independent predictors of mortality (OR, 95%CI) included age ≥ 80 years (3.78, 2.66-5.39), procalcitonin > 1 ng/mL (OR 4.07, 2.54-6.52), interleukin-6 (IL-6) > 100 pg/mL (OR 2.24, 1.53-3.27), and oxygen therapy at admission (OR 9.41, 5.22-16.97). Predictors of mechanical ventilation were age ≥ 80 years (7.14, 1.75-33.33), procalcitonin > 1 ng/mL (OR 2.09, 1.2-3.63), IL-6 > 100 pg/mL (OR 2.3, 1.4-3.78), and CRP at admission (OR 1.82, 1.15-2.88). <b>Conclusions</b>: Sex-related disparities in clinical presentation, laboratory profiles, and treatment strategies were evident, but mortality differences were driven primarily by age and inflammatory burden rather than sex alone. Elevated procalcitonin, high IL-6, and early oxygen requirement emerged as robust predictors of poor outcomes.