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

• DOI: 10.1371/journal.pone.0246771
• Publication Date: 2021-02-09T01:41:10Z
• Authors: Giorgia Montrucchio; Gabriele Sales; Francesca Rumbolo; Filippo Palmesino; Vito Fanelli; Rosario Urbino; Claudia Filippini; Giulio Mengozzi; Luca Brazzi
• Keywords: Adult; Calcitonin; Male; Science; Critical Illness; Kaplan-Meier Estimate; Fibrin Fibrinogen Degradation Products; Adrenomedullin; 03 medical and health sciences; Patient Admission; 0302 clinical medicine; Natriuretic Peptide, Brain; Humans; Aged; Q; R; COVID-19; Middle Aged; Prognosis; Peptide Fragments; 3. Good health; C-Reactive Protein; Logistic Models; Multivariate Analysis; Medicine; Female; Biomarkers; Research Article

Objective To 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.

Methods All 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.

Results 57 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]).

Conclusions In 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.