The widespread endothelial damage due to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. The aim of this study was to evaluate the role of Mid-regional proAdrenomedullin (MR-proADM) as a marker of SARS CoV2-related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS-CoV2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR-proADM cut-off values for ARDS development and mortality prediction were 3.04 nmol/L and 2 nmol/L, respectively. Patients presenting with MR-proADM values ≥ 2 nmol/L showed a significantly higher mortality risk. In conclusion, MR-proADM values ≥ 2 nmol/l identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.