Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study

Abstract

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR−) for mortality were 2.40 and 0.46, respectively. The LR+ and LR− for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62–0.81) and 0.72 (95% CI, 0.62–0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

Mid-Regional Pro-Adrenomedullin as a Prognostic Factor for Severe COVID-19 ARDS

“…Regarding mortality risk stratification, our results are in line with previous studies performed in the ICU population showing AUROCs between 0.73 and 0.85 for 28-day mortality, with optimal cut-points between 1 and 1.8 nmol/L [ 18 , 19 , 20 ]. We used cut-points according to the MR-proADM distribution and previous studies to avoid overfitting [ 25 ].…”

“…Being a marker of endothelial dysfunction, MR-proADM has been investigated in SARS-CoV-2 infection. Higher levels have been associated with mortality in the general population [ 12 , 13 , 14 , 15 ] and MR-proADM appeared to be a good risk stratification tool in the specific settings of the Emergency Room [ 16 , 17 ] and the ICU [ 18 , 19 , 20 ]. However, studies performed in the ICU setting used small patient samples with high heterogeneity of patient severity [ 21 ] and measured outcomes ≤ 30 days after ICU admission, which may be insufficient for such a study population.…”

Proadrenomedullin in the Management of COVID-19 Critically Ill Patients in Intensive Care Unit: A Systematic Review and Meta-Analysis of Evidence and Uncertainties in Existing Literature

“…Four papers were then excluded because they did not match the inclusion criteria. After an additional literature check, three papers were included in the systematic review [ 13 , 14 , 15 ]. A total of 20 articles were submitted to the systematic review.…”

“… Forest plot of the hypothetical meta-analyzed results [ 14 , 28 , 33 ]. One of the four studies selected could not be included as it did not report the standard deviation.…”

Special Issue “COVID-19 and Thrombosis”

“…Endothelial dysfunctions remain for a long time due to cytokine storm, and this abnormality may induce a persistent prothrombotic state. Therefore, many other transient risk factors may induce further pathophysiological changes that are associated with a worsening prognosis [ 4 , 5 , 6 , 7 ].…”