MR‐proADM as marker of endotheliitis predicts COVID‐19 severity

García de Guadiana‐Romualdo, Luis; Calvo Nieves, María Dolores; Rodríguez Mulero, María Dolores; Calcerrada Alises, Ismael; Hernández Olivo, Marta; Trapiello Fernández, Wysali; González Morales, Mercedes; Bolado Jiménez, Cristina; Albaladejo‐Otón, María Dolores; Fernández Ovalle, Hilda; Conesa Hernández, Andrés; Azpeleta Manrique, Eugenio; Consuegra‐Sánchez, Luciano; Nogales Martín, Leonor; Conesa Zamora, Pablo; Andaluz‐Ojeda, David

BACKGROUND: Early identification of patients at high risk of progression to severe COVID‐19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between endotheliitis and severe COVID‐19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid‐regional proadrenomedullin (MR‐proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS‐CoV‐2‐infected patients. METHODS: Prospective observational study enrolling adult patients with confirmed COVID‐19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28‐day all‐cause mortality and severe COVID‐19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints. RESULTS: A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28‐day mortality rate was of 14.1%. MR‐proADM showed the highest AUC to predict 28‐day mortality (0.905; [CI] 95%: 0.829‐0.955; P < .001) and progression to severe disease (0.829; [CI] 95%: 0.740‐0.897; P < .001), respectively. MR‐proADM plasma levels above optimal cut‐off (1.01 nmol/L) showed the strongest independent association with 28‐day mortality risk (hazard ratio [HR]: 10.470, 95% CI: 2.066‐53.049; P < .005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458‐31.750; P = .015). CONCLUSION: Mid‐regional proadrenomedullin was the biomarker with highest performance for prognosis of death and progression to severe disease in COVID‐19 patients and represents a promising predictor for both outcomes, which might constitute a potential tool in the assessment of prognosis in early stages of this disease.