Critical and non-critical coronavirus disease 2019 patients: which is the most predictive biomarker for disease severity and outcome?: A multicentre prospective cohort study comparing mid-regional pro-adrenomedullin, inflammatory and immunological patterns.

Abstract

Background: Severe acute respiratory syndrome-coronavirus-2 in coronavirus disease 2019 (COVID-19) patients leads to a wide range of clinical manifestations. The evaluation of mid-regional pro-adrenomedullin (MR-proADM) as a prognostic biomarker in noncritical wards (NON-ICU) and intensive care units (ICU), may have a potential in predicting disease severity and outcomes.

Objective: To assess the difference in the prognostic power of MR-proADM in NON-ICU wards and in ICUs in a prospective multicentre cohort study.

Design: From January to July 2021, all adult COVID-19 patients requiring admission for more than 48 h.

Setting: One primary centre and two secondary centre hospitals.

Patients: One hundred and twenty-three ICU and 77 NON-ICU patients.

Intervention: MR-proADM, lymphocyte subpopulations and immunoglobulins were measured within 48 h and on days 3 and 7. A Log-rank test was used to compare survival curves, using a MR-proADM cut-off value of 1.5 nmol l^-1. The predictive ability for mortality was compared using the area under the curve and 95% confidence interval (CI) of different receiver-operating characteristic curves.

Main outcome measures: The first 48 h MR-proADM values were significantly higher in the ICU group (median value 1.10 [IQR, 0.80 to 1.73] pg ml^-1 vs. 0.90 [0.70 to 1.20] pg ml^-1, P = 0.020), and statistically significant changes were observed over time for MR-proADM, CD3+, CD4+ and CD56+. In univariate analysis, MR-proADM was the only biomarker that significantly predicted mortality (P = 0.006). The logistic regression model showed an odds ratio for mortality equal to 1.83 (95% CI, 1.08 to 3.37) P = 0.035 for MR-proADM, 1.37 (1.15 to 1.68) P = 0.001 for MuLBSTA and 1.11 (1.05 to 1.18) P less than 0.001 for SAPS II.

Conclusion: MR-proADM admission values and trends over time appear to be a suitable marker of illness severity and a patient's risk of mortality in both ICU and NON-ICU settings. Lymphocyte subpopulation dysfunction seems to play a role in defining the severity of COVID-19 but is limited to ICU setting.

Trial registration: on clinicaltrials.gov, NCT04873388 registered on March 2020.