Dynamic Cytokine and Coagulation Profiling in Patients With Severe COVID‑19 Evaluated for Pulmonary Embolism: A...

BACKGROUND COVID-19 is associated with immune dysregulation and an increased risk of thromboembolic complications, including pulmonary embolism (PE). Identification of dynamic immunological predictors of adverse outcomes remains clinically relevant. This study evaluated associations between coagulation, inflammatory, immunological markers, and in-hospital mortality in patients with severe COVID-19. MATERIAL AND METHODS In this prospective observational study, 47 hospitalized adults with severe COVID-19 and suspected PE were enrolled. Serum cytokines, coagulation parameters, and cardiac injury biomarkers were assessed at enrollment and on hospital day 5. PE was confirmed using computed tomography pulmonary angiography. Univariable and multivariable binary logistic regression was used to identify predictors of in-hospital all-cause mortality. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), with internal validation by bootstrap resampling. RESULTS PE was diagnosed in 19 patients (40.4%), and 13 patients (27.7%) died during hospitalization. Higher standardized day-5 interleukin (IL)-9 and IL-15 levels were associated with mortality in univariable analyses, but neither remained significant after Benjamini-Hochberg false discovery rate correction across the panel of 15 cytokines measured on day 5 (IL-9, q=0.180; IL-15, q=0.210). In an age-adjusted model, day-5 IL-9 remained associated with mortality (adjusted odds ratio per 1-SD increase, 3.331; 95% CI, 1.289-8.608; P=0.013). Apparent discrimination was moderate (AUC 0.774; 95% CI, 0.563-0.984; P=0.011), but bootstrap validation showed marked coefficient instability. CONCLUSIONS Day-5 IL-9 levels may reflect an evolving risk in severe COVID-19, but the association was sensitive to multiple-testing correction and model instability. This study's findings are exploratory and require confirmation in larger, externally validated cohorts.