Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin

Abstract

Background Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. Conclusions This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe.

Endothelial Damage, Neutrophil Extracellular Traps and Platelet Activation in COVID-19 vs. Community-Acquired Pneumonia: A Case–Control Study

“…Higher endothelial damage biomarkers (ProADM and proendothelin) showed greater predictive mortality value compared to C-reactive protein, procalcitonin, and Ddimer [26,49]. Elevated levels of proADM (>1.76 nmol/L) or proendothelin (>75 nmol/L) were associated with a higher rate of ICU admission, in-hospital mortality, and shorter time to death [26], as seen in other series of cases [50,51]. Notably, initial levels of CitH3, cfDNA, and sP-selectin were not associated with higher mortality.…”

Plasma bioactive adrenomedullin predicts mortality and need for dialysis in critical COVID-19

“…In one study, MR-proADM levels on hospital admission showed excellent predictive value for 28-day mortality in COVID-19 patients with an AUC of 0.91 and were also highly predictive of progression to severe disease 21 . Other studies on MR-proADM have also shown good prediction with an area under the curve of approximately 0.80 [22][23][24] , which suggests that bio-ADM has an important pathophysiological role in COVID-19.…”

“…Recently, several studies have shown a relationship between high levels of adrenomedullin and severity of illness in hospitalized COVID-19 patients [21][22][23][24][25][26] . Adrecizumab has been tested to treat severe COVID-19 ARDS in a small uncontrolled case series 27 .…”

“…In one study, MR-proADM levels on hospital admission showed excellent predictive value for 28-day mortality in COVID-19 patients with an AUC of 0.91 and were also highly predictive of progression to severe disease 21 . Other studies on MR-proADM have also shown good prediction with an area under the curve of approximately 0.80 [22][23][24] , which suggests that bio-ADM has an important pathophysiological role in COVID-19.Only two studies have investigated the association between bio-ADM and COVID-19 mortality. In a Dutch study of 80 patients, bio-ADM levels on day 7 from ICU admission predicted mortality with an AUC of 0.70 for 28-day mortality.…”

“…Adrecizumab has been tested to treat severe COVID-19 ARDS in a small uncontrolled case series 27 . Studies of the association between adrenomedullin and COVID-19 have mainly been performed on MR-proADM [21][22][23][24] , and have consistently shown elevated levels in non-survivors compared to survivors 28 . In one study, MR-proADM levels on hospital admission showed excellent predictive value for 28-day mortality in COVID-19 patients with an AUC of 0.91 and were also highly predictive of progression to severe disease 21 .…”