MR-proADM as Prognostic Factor of Outcome in COVID-19 Patients

Abstract

Background: Serum mid-regional proadrenomedullin (MR-proADM) has emerged as a marker of organ failure (mainly lungs and kidneys) and poor prognosis in patients admitted to intensive care (IC); some reports also suggest it and other markers, such as Krebs von den Lungen-6 (KL-6) and interleukin-6 (IL-6), as a prognostic biomarker of COVID-19. The aim of the study was to evaluate the performance MR-proADM in hospitalized COVID-19 patients for predicting in-hospital mortality and need for non-invasive or invasive respiratory support.

Methods: We enrolled 74 patients hospitalized in the COVID Unit of Siena Hospital from March to May 2020, for whom serum samples were available on admission for assay of MR-proADM, KL-6 and IL-6. Demographic data, comorbidities, medical history and clinical laboratory data on days 1-3 of admission and Simplified Acute Physiology Score and Simplified Organ Failure Assessment scores calculated at day 1 were collected retrospectively, as well as mortality and IC admission data.

Results: 12 patients died in hospital (16%) and 14 patients were admitted to IC (19%). Serum concentrations of MR-proADM on admission and on day 1 were higher among non-survivors than among survivors (p = 0.015 and p = 0.045, respectively), while those on day 3 were not significantly different. Patients needing respiratory support had higher MR-proADM concentrations on admission than the others (p = 0.046), and those requiring invasive mechanical ventilation had higher MR-proADM on day 1 (p = 0.017). Serum concentrations of KL-6 and IL-6 were significantly higher in non-survivors (p = 0.03 and p = 0.004, respectively). ROC curve analysis showed that serum MR-proADM on day 1 had the best accuracy in predicting death and/or IC admission (AUC = 0.9583, p = 0.0006); the combination of all three biomarkers further improved the accuracy of prediction of death or IC admission (AUC = 0.9793; p = 0.00004).

Conclusions: Our data sustain the potential of serum MR-proADM as a reliable prognostic biomarker of hospitalized COVID-19 patients and confirms the utility of the three markers in the management and risk stratification of hospitalized patients. The markers are collected mini-invasively and are quick to analyze and cost-effective.

Keywords: COVID-19; KL-6; biomarkers; proADM.

Figure 1

Flow diagram describing the enrollment of study population. Blood samplings at admission and day 1 of hospital stay were available for all patients included in the study. Two patients were admitted to ICU by day 3.

Figure 2

Comparison of serum biomarkers’ concentrations between survivors (green box) and non-survivors (red box). All serum biomarkers, with the exception of MR-proADM at day 3, were significantly higher in patients with a negative outcome than in patients who were discharged. KL-6 and IL-6 levels were measured at hospital admission. Data are expressed as median ± interquartile range. MR-proADM, KL-6 and IL-6 levels are expressed as µmoL/L, U/mL and pg/mL, respectively. *: p < 0.05; **: p < 0.001. Abbreviations: ns, not significant; KL-6, Krebs von den Lungen-6; IL-6, interleukin-6.

Figure 3

Comparison of ROC curve analysis curves between MR-proADM at day 1 and the combination of MR-proADM at day 1 plus KL-6 at admission and IL-6 at admission for predictive accuracy of death or ICU admission. The combination of three biomarkers shows a higher accuracy in predicting a negative outcome than MR-proADM at day 1 alone, though not significantly (difference of AUC = 0.021, p = 0.7021). MR-proADM: Mid-Regional proadrenomedullin.