MR-proADM as prognostic factor of outcome in COVID-19 patients

Abstract

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893–11.413], together with increased neutrophil count (OR = 1.029 [1.011–1.049]) and WHO disease severity class (OR = 7.632 [5.871–19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771–0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728–0.987] and a specificity of 0.687 [95% Cl 0.587–0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.

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

“…In COVID-19, several studies have studied the potential role of MR-proADM for prognosis of short-term mortality [ García de Guadiana-Romualdo et al, 2021 ; Gregoriano et al, 2021 ; Montrucchio et al, 2021 ], progression to severe disease [García de Guadiana et al, 2021; Sozio et al, 2021 ] and requirement of renal replacement therapy in critically ill patients [Roedl et al; 2021] . The main limitations in these studies are the small sample size and the inclusion of patients recruited in the first wave, in which the role of laboratory test has been recently disputed, with differences in the prognostic value of some thromboinflammation markers in comparison to the first wave.…”

“…Preliminary results in small scale studies including patients on first wave suggest a potential role for MR-proADM regarding prognosis [García de Guadiana-Romualdo et al,2021 ; Gregoriano et al, 2021 ; Sozio et al, 2021 ; Montrucchio et al, 2020], but these findings need confirmation in larger studies trials [Saeed et al, 2021] . Noteworthy, most of these studies focused on a short follow-up period to outcome (28/30 days) [ García de Guadiana-Romualdo et al, 2021 ; Gregoriano et al, 2021 ].…”

Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: A prospective cohort study

“…Baseline MR-proADM performed well in predicting 28-day mortality in comparison with APACHE II and Simplified Acute Physiology Score II (SAPSII) when all patients admitted to the ICU were included [ 23 ]. The value of MR-proADM as prognostic marker in adult patients hospitalized with SARS-CoV-2 infection was studied in several observational studies [ [24] , [25] , [26] , [27] , [28] , [29] ]. Increased levels of MR-proADM were independently associated with mortality [ [24] , [25] , [26] , [27] , [28] , [29] ].…”

“…The value of MR-proADM as prognostic marker in adult patients hospitalized with SARS-CoV-2 infection was studied in several observational studies [ [24] , [25] , [26] , [27] , [28] , [29] ]. Increased levels of MR-proADM were independently associated with mortality [ [24] , [25] , [26] , [27] , [28] , [29] ]. However, not all patients were admitted to the ICU [ 24 , 25 , 28 , 29 ].…”

“…Increased levels of MR-proADM were independently associated with mortality [ [24] , [25] , [26] , [27] , [28] , [29] ]. However, not all patients were admitted to the ICU [ 24 , 25 , 28 , 29 ]. CT-proET-1 was studied in non-COVID-19 patients admitted to the ED with CAP [ 14 , 16 ].…”