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

Abstract

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.

Plasma Levels of Mid-Regional Proadrenomedullin Accurately Identify H1N1pdm09 Influenza Virus Patients with Risk of Intensive Care Admission and Mortality in the Emergency Department

“…On the other hand, the ADM is present in an important way in the capillary endothelium, where it maintains muscle relaxation, perfusion, and permeability, being responsible for the integrity of the capillary [33,34]. Our results are similar to those published in the last two years in SARS-CoV-2 patients, where several medium-size studies have unanimously defined MR-proADM as a marker with the ability to predict mortality [35][36][37], admission to the ICU [36,38], the appearance of ARDS [39], and the need for intubation and mechanical ventilation [36,39] or renal replacement techniques [40] in patients with COVID-19. These 12 studies add up to a total of 1316 patients.…”

“…These 12 studies add up to a total of 1316 patients. In the largest, García Guadiana et al [36] included 356 patients with an ICU admission of 29.5% and a mortality rate of 8.9%. The MR-proADM values predicted mortality at 90 days with an AUC-ROC of 0.832.…”

Adrenomedullin Therapy in Moderate to Severe COVID-19

“…MR-proADM, an AM synthesis marker, has been recognized as the best marker for sensitivity and specificity in sepsis endothelial dysfunction [101]. A significant MR-proADM increase has been reported in patients with COVID-19, especially in severe conditions, such as acute respiratory distress syndrome (ARDS) [26][27][28][29][30][31][32][33][34][35][36]. More importantly, increased MR-proADM is the best predictor of mortality in patients with COVID-19; the area under the receiver operating characteristic curve (ROC AUC) was distributed in a high range (0.78-0.951) [27][28][29][31][32][33][34][35].…”

“…A significant MR-proADM increase has been reported in patients with COVID-19, especially in severe conditions, such as acute respiratory distress syndrome (ARDS) [26][27][28][29][30][31][32][33][34][35][36]. More importantly, increased MR-proADM is the best predictor of mortality in patients with COVID-19; the area under the receiver operating characteristic curve (ROC AUC) was distributed in a high range (0.78-0.951) [27][28][29][31][32][33][34][35]. MR-proADM plasma concentrations in COVID-19 survivors did not increase after hospital admission; however, concentrations increased significantly in non-survivors [35].…”

“…AM decreases tissue injury by improving cytokine control and the barrier function of endothelial cells. Contrarily, AM plasma concentration and related proAM fragments were shown to increase in patients with COVID-19, and more importantly, the increase in AM was closely related to the prognosis of patients with COVID-19 [26][27][28][29][30][31][32][33][34][35][36]. These data suggest that AM plays an important role in COVID-19 pathophysiology; thus, it could be a candidate alternative treatment for COVID-19.…”