ABSTRACT
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.