Background/Objectives: Although COVID-19 is generally more severe in males, data on sex-specific differences in the predictive value of commonly used inflammatory biomarkers remain limited. The study aimed to evaluate the sex-specific prognostic performance of selected biomarkers during the Alpha variant wave. Methods: In single-center study, univariate and multivariable regressions analyses, along with receiver operating characteristic curve (ROC) analyses, were performed to assess the association of acute-phase proteins, cytokines, and white blood cell indices (at admission and 7 days later) and disease severity and mortality in patients with severe-to-critical COVID-19. Results: At admission, the combined assessment of ferritin and D-dimer predicted disease severity in both sexes; however, optimal cut-off values and diagnostic performance (specificity and sensitivity) differed between males and females. In males, neutrophil and lymphocyte counts provided additional clinically relevant predictive value. Seven days after admission, the combination of ferritin, D-dimer, and fibrinogen in males, and ferritin, as an independent predictor within a model including lactate dehydrogenase, in females demonstrated strong predictive performance for severe-to-critical COVID-19. At this time-point, lymphocyte count in males was also identified as an independent predictor of disease severity. Notably, C-reactive protein and neutrophil count correlated with mortality in males with severe-to-critical disease. Conclusions: Severe COVID-19 is predicted by distinct acute-phase proteins and shared, sex-specific biomarkers, but with distinct cut-offs and predictive accuracy. In males, white blood cell indices also serve as independent predictors. Furthermore, prognostic utility changes of these biomarkers over the course of the disease, suggesting sex-specific and time-dependent role in COVID-19 pathogenesis.

Background/Objectives: While COVID-19 is typically more severe in males, there is limited data on sex-specific differences in the predictive value of common inflammatory biomarkers. To address this gap, their predictive capacity was evaluated in a single-center study of male and female patients during the Alpha variant wave. Methods: Univariate, multivariable, and receiver operating characteristic (ROC) analyses were used to evaluate the association of acute-phase proteins, cytokines, and white blood cell counts (measured on admission and day seven) with COVID-19 severity and mortality in severely/critically ill COVID-19 subjects. Results: On admission, the combination of ferritin and D-dimer effectively predicted disease severity in both sexes, though cut-off values and diagnostic accuracy (specificity and sensitivity) varied by sex. In males, neutrophil and lymphocyte counts provided additional clinically relevant predictive value. Seven days post-admission the combination of ferritin, D-dimer and fibrinogen in males and ferritin (as independent predictor comprising model with lactate dehydrogenase) in females emerged as efficient predictors of severe/critical COVID-19. On this evaluation-point, lymphocytes in males and neutrophil-to-lymphocyte ratio in females were also identified as independent predictors of severe/critical COVID-19. Notably, on this evaluation-point C-reactive protein and neutrophil count independently predicted mortality in males with severe/critical disease. Conclusion: Different acute-phase proteins (or the same proteins with distinct cut-off values and predictive characteristics) and white blood cell indices should be considered as independent predictors of severe/critical COVID-19 in males and females and ii) the prognostic capacity of many of them evolves during disease progression, indicating their sex-specific, time-dependent pathogenetic role in COVID-19.