Inflammatory–Thrombotic Phenotypes and Outcomes in COVID-19-Associated Pulmonary Embolism: A Single-Center Cohort Study

<b>Background and Objectives</b>: Pulmonary embolism (PE) complicating COVID-19 combines viral pneumonia with immunothrombosis, but the relative prognostic value of comorbidities, embolic burden, lung involvement, and inflammatory markers is uncertain. We aimed to characterize clinical profiles and identify independent predictors of respiratory failure and in-hospital mortality in COVID-19-associated PE. <b>Materials and Methods</b>: We performed an observational single-center study including 161 adults with RT-PCR-confirmed COVID-19 and CTPA-confirmed acute PE. Demographic data, comorbidities, CT lung involvement, biomarkers, and treatments were compared across outcomes, and multivariable logistic regression and principal component analysis (PCA) were used to model risk. <b>Results</b>: In-hospital mortality was 24.8% (40/161), and invasive mechanical ventilation was 18.6% (30/161). Classical PE variables (Wells score, PESI, thrombus location, D-dimer) and comorbidities showed limited discrimination, whereas severe CT lung involvement independently predicted death (OR 4.46; 95% CI 1.55-12.86) and intubation (OR 8.88; 95% CI 2.92-27.04). Each 50 mg/L increase in CRP increased mortality odds by 41% (OR 1.41; 95% CI 1.02-1.96), and a 10-fold rise in IL-6 (log10 IL-6) was associated with six-fold higher mortality (OR 6.10; 95% CI 1.84-20.18). PCA identified a hyperinflammatory-thrombotic component (PC1); per 1-SD increase in standardized PC1, the odds of intubation or death rose 3.5-fold (OR 3.50; 95% CI 2.05-5.99), and event rates across PC1 tertiles were 7.4%, 20.8%, and 57.4%. <b>Conclusions</b>: In COVID-19-related PE, integrated immunothrombotic activation and extent of lung involvement, rather than embolic burden alone, drive early critical outcomes and may support refined risk stratification.