Integrated Echocardiographic and Biomarker Assessment Reveal Progressive Cardiovascular Injury After Moderate and Severe COVID‐19

ABSTRACT Background COVID‐19 has been associated with significant cardiovascular complications, yet the long‐term cardiovascular consequences and prognostic biomarkers in moderate versus severe disease remain incompletely characterized. This study aimed to evaluate longitudinal cardiovascular changes, identify mortality predictors, and assess the discriminative performance of fractional exhaled nitric oxide (FeNO) and endothelin‐1 (ET‐1) in hospitalized COVID‐19 survivors. Methods This prospective cohort study enrolled 480 hospitalized COVID‐19 patients (240 moderate, 240 severe by WHO criteria) who survived to discharge between June 2020 and December 2023. Baseline and 1‐year echocardiography, inflammatory biomarkers including FeNO and ET‐1, and clinical outcomes were assessed. Multivariable Cox regression identified mortality predictors, and ROC analysis evaluated biomarker discriminative performance. Results Severe COVID‐19 patients demonstrated significant baseline right ventricular dysfunction with reduced TAPSE (16.63 ± 2.43 vs. 20.36 ± 3.68 mm, p < 0.001) and impaired RVPA coupling (0.60 ± 0.14 vs. 0.88 ± 0.45, p < 0.001). Progressive cardiovascular deterioration occurred over 1 year, with pulmonary artery pressure increasing 17.8% in severe versus 7.1% in moderate disease. Two‐year mortality was 16.9% overall. Independent mortality predictors included hypertension (HR 3.02), hyperlipidemia (HR 2.51), diabetes (HR 2.23), and left atrial volume index (HR 1.08 per mL/m 2 ). FeNO and ET‐1 predicted mortality specifically in severe disease (HR 1.028 and 1.035, respectively) and demonstrated excellent discriminative ability (AUC 0.892 and 0.865) for identifying severe COVID‐19. Conclusions Moderate and severe COVID‐19 survivors exhibit progressive cardiovascular deterioration, particularly affecting right ventricular function. FeNO and ET‐1 serve as severity‐specific prognostic biomarkers and demonstrate excellent discriminative performance, supporting their integration into risk stratification protocols for COVID‐19 survivors.