Endothelial dysfunction and Mid-Regional proAdrenomedullin: What role in SARS-CoV-2 infected Patients?

Abstract

Background Endothelial dysfunction, a major complication of SARS-CoV-2 infectionplaying a key-role in multi-organ damage, carries high risk of mortality. Aim To investigate the potential role of Mid-Regional pro-Adrenomedullin (MR-proADM) in detecting endothelial damage with a view to stratifying the risk of adverse events (length of stay, death, admission in Intensive Care Unit) and/or disease resolution. Materials and Methods In 135 consecutive patients with SARS-CoV-2 infection, MR-proADM was measured in EDTA-K2 plasma samples using B.R.A.H.M.S. KRYPTOR® COMPACT Plus method (Thermo Fisher Scientific, Hennigsdorf, Germany) Results Patients were subdivided into three groups based on their MR-proADM value (nmol/L): 1 (n=20, MR-proADM≤0.55); 2 (n=82, 0.55<MR-proADM≤1.50); 3 (n=33, MR-proADM>1.50). The higher the MR-proADM value, the greater the patients’ age, the more frequent the occurrence of pneumonia, the requiring of more aggressive treatment, the longer the hospitalization and the more frequent a fatal event . Significant differences were found between the three groups for MR-proADM, White-blood cell count, Neutrophil count, D-dimer, C-reactive Protein, Procalcitonin and hs-Troponin I. At logistic regression,it was found that MR-proADM and Log 10 D-dimer were the most significant predictors of adverse events. Conclusion The findings made in the present study highlight the relevance of MR-proADM values in providing clinically useful information, particularly for stratifying COVID-19 patients according to the risk of a more severe form of disease and to the development of adverse events.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study

“…To our knowledge, this is the largest study evaluating the role of MR-proADM in critically ill COVID-19 patients. Other studies have evaluated the role of MR-proADM in the setting of COVID-19 pandemic [22][23][24][25][26][27][28][29][30]. Benedetti et al [22] evaluated MR-proADM and other biomarkers in 21 ICU patients (measured on the 1st, 2nd, 3rd, and 5th day of admission) to determine their predictive value for mortality; the optimal cut-off for MR-proADM was 1.07 nmol/L (sensitivity of 91% and specificity of 71%; p = 0.006).…”

“…The optimal cut-off point for predicting mortality was 0.93 nmol/L. Zaninotto et al [29] retrospectively evaluated the potential role of MR-proADM in detecting endothelial dysfunction and its usefulness for stratifying COVID-19 patients; with a median time elapsed from the hospital admission to MR-proADM measurement of 7 days. A total of 135 patients were included, and the findings suggested that higher MR-proADM levels are associated with a greater risk for adverse outcomes.…”

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.…”