Circulating MR-proADM levels, as indicator of endothelial dysfunction, for early risk stratification of mid-term mortality in COVID-19 patients

de Guadiana-Romualdo, Luis García; Martínez, Monica Martínez; Mulero, María Dolores Rodríguez; Torrella, Patricia Esteban; Olivo, Marta Hernández; García, María José Alcaraz; Campos-Rodríguez, Valerio; Sancho-Rodríguez, Natalia; Martínez, María Galindo; Alcaraz, Antonia; Braquehais, María Salome Ros; Perez-Crespo, Carlos Báguena; Arenas, Verónica Ramos; Jiménez, Cristina Tomás; Consuegra-Sánchez, Luciano; Conesa-Hernandez, Andrés; Piñera-Salmerón, Pascual; Bernal-Morell, Enrique

OBJECTIVES: Thromboinflammation, resulting from a complex interaction between trombocytopathy, coagulopathy and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system dysruption leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients. METHODS: Prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival to emergency department. The primary endpoint was 90-day mortality. Area under the curve (AUC) and Cox regression analysis were used to assess its discriminatory ability and association with the endpoint. RESULTS: A total of 359 patients were enrolled and 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cut-off of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including 11 potential confounders, were a independent predictor of 90-day mortality (HR: 0.162 [95% CI: 0.043-0.480]) CONCLUSIONS: Our data confirms that MR-proADM has a role for mid-term prognosis of COVID-19 patients and might assist to physicians for risk stratification.