MR-proADM as marker of endotheliitis predicts COVID-19 severity

Eur J Clin Invest. 2021 May;51(5):e13511. doi: 10.1111/eci.13511. Epub 2021 Feb 20.

Abstract

Background: Early identification of patients at high risk of progression to severe COVID-19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between endotheliitis and severe COVID-19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid-regional proadrenomedullin (MR-proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS-CoV-2-infected patients.

Methods: Prospective observational study enrolling adult patients with confirmed COVID-19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28-day all-cause mortality and severe COVID-19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints.

Results: A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28-day mortality rate was of 14.1%. MR-proADM showed the highest AUC to predict 28-day mortality (0.905; [CI] 95%: 0.829-0.955; P < .001) and progression to severe disease (0.829; [CI] 95%: 0.740-0.897; P < .001), respectively. MR-proADM plasma levels above optimal cut-off (1.01 nmol/L) showed the strongest independent association with 28-day mortality risk (hazard ratio [HR]: 10.470, 95% CI: 2.066-53.049; P < .005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458-31.750; P = .015).

Conclusion: Mid-regional proadrenomedullin was the biomarker with highest performance for prognosis of death and progression to severe disease in COVID-19 patients and represents a promising predictor for both outcomes, which might constitute a potential tool in the assessment of prognosis in early stages of this disease.

Keywords: COVID-19; SARS-CoV-2; endotheliitis; mid-regional proadrenomedullin; prognosis; severity.

Publication types

  • Observational Study

MeSH terms

  • Adrenomedullin / blood*
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • COVID-19 / blood*
  • COVID-19 / mortality
  • Cause of Death
  • Disease Progression
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Inflammation / blood*
  • Intensive Care Units / statistics & numerical data
  • Male
  • Middle Aged
  • Mortality*
  • Peptide Fragments / blood*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Protein Precursors / blood*
  • Respiration, Artificial / statistics & numerical data
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Peptide Fragments
  • Protein Precursors
  • mid-regional pro-adrenomedullin, human
  • Adrenomedullin