Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: An observational prospective study.

Giorgia Montrucchio,Luca Brazzi,Francesca Rumbolo,Rosario Urbino,Vito Fanelli,Giulio Mengozzi,Gabriele Sales,Claudia Filippini,Filippo Palmesino,Pablo Garcia De Frutos

doi:10.1371/journal.pone.0246771

Abstract

ObjectiveTo test the effectiveness of mid-regional pro-adrenomedullin (MR-proADM) in comparison to C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH) in predicting mortality in COVID-19-ICU-patients.MethodsAll consecutive COVID-19 adult patients admitted between March and June 2020 to the ICU of a referral, university hospital in Northern-Italy were enrolled. MR-proADM and routine laboratory test were measured within 48 hours from ICU admission, on day 3, 7 and 14. Survival curves difference with MR-proADM cut-off set to 1.8 nmol/L were tested using log-rank test. Predictive ability was compared using area under the curve and 95% confidence interval of different receiver-operating characteristics curves.Results57 patients were enrolled. ICU and overall mortality were 54.4%. At admission, lymphocytopenia was present in 86% of patients; increased D-dimer and CRP levels were found in 84.2% and 87.7% of patients respectively, while PCT values > 0.5 μg/L were observed in 47.4% of patients. MR-proADM, CRP and LDH were significantly different between surviving and non-surviving patients and over time, while PCT, D-dimer and NT-pro-BNP did not show any difference between the groups and over time; lymphocytes were different between surviving and non-surviving patients only. MR-proADM was higher in dying patients (2.65±2.33vs1.18±0.47, p<0.001) and a higher mortality characterized patients with MR-proADM >1.8 nmol/L (p = 0.016). The logistic regression model adjusted for age, gender, cardiovascular disease, diabetes mellitus and PCT values confirmed an odds ratio = 10.3 [95%CI:1.9–53.6] (p = 0.006) for MR-proADM >1.8 nmol/L and = 22.2 [95%CI:1.6–316.9] (p = 0.022) for cardiovascular disease. Overall, MR-proADM had the best predictive ability (AUC = 0.85 [95%CI:0.78–0.90]).ConclusionsIn COVID-19 ICU-patients, MR-proADM seems to have constantly higher values in non-survivor patients and predict mortality more precisely than other biomarkers. Repeated MR-proADM measurement may support a rapid and effective decision-making. Further studies are needed to better explain the mechanisms responsible of the increase in MR-proADM in COVID-19 patients.

Highlights

From December 2019, when the coronavirus disease (COVID-19) first emerged in Wuhan (China), a total of over 19 million COVID-19 cases and 720,000 deaths have been reported globally [1]
Lymphocytopenia was present in 86% of patients; increased D-dimer and C-reactive protein (CRP) levels were found in 84.2% and 87.7% of patients respectively, while PCT values > 0.5 μg/L were observed in 47.4% of patients
Prospective, single-centre study conducted between March and June 2020 at the “Città della Salute e della Scienza” University Hospital (Turin, Northern Italy) in Effectiveness of mid-regional pro-adrenomedullin as prognostic marker in COVID-19 critically ill patients the regional referral Intensive Care Units (ICU) for the treatment of severe respiratory failure and Extracorporeal Membrane Oxygenation (ECMO) support in combination with two new temporary ICUs created to face the COVID-19 pandemic

Summary

Introduction

From December 2019, when the coronavirus disease (COVID-19) first emerged in Wuhan (China), a total of over 19 million COVID-19 cases and 720,000 deaths have been reported globally [1]. As in any context of urgency, finding a biomarker able to identify more severe cases is an objective either desired or difficult to achieve. In COVID-19 pandemic, multiple indicators were able to highlight increased severity, especially if combined together [3], but none have been proved entirely effective. ADM is a multipotent regulatory peptide with a number of biological activities—vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator— widely expressed throughout the body, including bone, adrenal cortex, kidney, lung, blood vessels and heart. It is upregulated by hypoxia, inflammatory cytokines, bacterial products and shear stress [6]. ADM is even present in pulmonary pneumocytes type 2, smooth muscle cells, neurons and immune cells [7], making it a promising molecule to investigate in relation to ARDS, as realized after cardiac surgery [8]

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