04 Mar MR-proADM as marker of endotheliitis predicts COVID-19 severity
García de Guadiana-Romualdo L, Calvo Nieves MD, Rodríguez Mulero MD, Calcerrada Alises I, Hernández Olivo M, Trapiello Fernández W, et al.
ABSTRACT
Background: Early identification of patients at high risk of progression to severe COVID-19 has been an unresolved challenge. Although there is increasing evidence showing a direct association between endothelitis and severe COVID-19, the role of endothelial damage and biomarkers has hardly been studied. The relationship between circulating levels of midregional proadrenomedullin (MR-proADM), a biomarker of endothelial dysfunction, and the prognosis of patients infected with SARS-CoV-2 is investigated.
Methods: Prospective observational study that included adult patients with confirmed COVID-19. On admission to the emergency department, a blood sample was drawn for laboratory analysis.
Primary and secondary endpoints were 28-day all-cause mortality and severe progression of COVID-19.
Area under the curve (AUC) and multivariate regression analysis were used to assess biomarker association with 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 14,1%.
- MR-proADM showed the highest AUC for predicting 28-day mortality (0,905; 95% [CI]: 0,829-0,955; p < 0,001) and progression to severe disease (0,829; 95% [CI]: 0,740- 0,897, p < 0,001), respectively.
- Plasma MR-proADM levels above the optimal cut-off point (1,01 nmol/L) showed a strong independent association with the risk of 28-day mortality (hazard ratio [HR]: 10,470, 95% CI: 2,066-53,049; p <0,005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458-31.750; p = 0.015).
Kaplan-Meier analysis showed that no patient with an MR-proADM value ≤0,88 nmol/L, recommended as the manufacturer's cutoff, died within the first 28 days after admission to the Emergency Department (Figure A ). Survival analysis for the Youden index cutoff is shown in Figure B.
The highest probability of progression to severe disease in patients with an MR-proADM level > 1.01 nmol/L is shown in Figure C.
A. Cumulative incidence of 28-day mortality during hospitalization stratified by MR-proADM at admission ≤ 0,88 nmol/L.
B. 28-day mortality during hospitalization stratified by MR-proADM on admission > 1,01 nmol/L.
C. Progression to severe disease stratified by MR-proADM on admission > 1,01 nmol/L.
Conclusion: MR-proADM was the highest performing biomarker for the prognosis of death and progression to severe disease in patients with COVID‐19 and represents a promising predictor for both outcomes, which could be a potential tool in prognostic assessment in early stages of COVID -19.