Presepsin as a diagnostic and prognostic biomarker of severe bacterial infections and COVID-19

Abstract

We aimed to develop presepsin as a marker of diagnosis of severe infections of either bacterial and viral origin. The derivation cohort was recruited from 173 hospitalized patients with acute pancreatitis or post-operative fever or infection suspicion aggravated by at least one sign of the quick sequential organ failure assessment (qSOFA). The first validation cohort was recruited from 57 admissions at the emergency department with at least one qSOFA sign and the second validation cohort from 115 patients with COVID-19 pneumonia. Presepsin was measured in plasma by the PATHFAST assay. Concentrations more than 350 pg/ml had sensitivity 80.2% for sepsis diagnosis in the derivation cohort (adjusted odds ratio 4.47; p < 0.0001). In the derivation cohort, sensitivity for 28-day mortality prognosis was 91.5% (adjusted odds ratio 6.82; p: 0.001). Concentrations above 350 pg/ml had sensitivity 93.3% for the diagnosis of sepsis in the first validation cohort; this was 78.3% in the second validation cohort of COVID-19 aiming at the early diagnosis of acute respiratory distress syndrome necessitating mechanical ventilation. The respective sensitivity for 28-day mortality was 85.7% and 92.3%. Presepsin may be a universal biomarker for the diagnosis of severe infections of bacterial origin and prediction of unfavorable outcome.

Figure 1

Study flowchart. The derivation cohort consisted of 173 patients recruited before the pandemic who had at least one sign of qSOFA. A cut-off of presepsin of more than 350 pg/ml was developed for the diagnosis of sepsis. This cut-off was validated in two cohorts: the validation cohort 1 was recruited from 57 consecutive admissions at the emergency department (ED) before the pandemic. The 350 pg/ml presepsin cut-off was applied for the diagnosis of sepsis the first 48 h post admission. The validation cohort 2 was recruited from 115 patients hospitalized for COVID-19 pneumonia. The 350 pg/ml presepsin cut-off was applied to demonstrate those who were in acute respiratory distress syndrome (ARDS) in need of mechanical ventilation (MV) the next 48 h.

Figure 2

Diagnostic performance of presepsin for Sepsis using the Sepsis-3 definitions in the derivation cohort. (A) Box plots of the concentrations of presepsin among patients without sepsis and patients with sepsis. The p-value of the comparisons by the Mann–Whitney U test is shown. (B) Receiver Operator Characteristics (ROC) curve of presepsin for the diagnosis of sepsis; (C) diagnostic performance of the 350 pg/ml cut-off of presepsin for the diagnosis of sepsis; (D) stepwise (forward) logistic regression analysis of variables associated with classification into sepsis; only variables remaining significant after four steps of analysis are provided. AUC area under the curve, CCI Charlson’s comorbidity index, CI confidence interval, COPD chronic obstructive pulmonary disease, CRP C-reactive protein, NPV negative predictive value, OR odds ratio, PPV positive predictive value, WBC white blood cell count.

Figure 3

Prognostic performance of presepsin for 28-day mortality in the derivation cohort. (A) Box plots of the concentrations of presepsin between survivors and non-survivors. The p-value of the comparison by the Mann–Whitney U test is shown. (B) prognostic performance of the 350 pg/ml cut-off of presepsin for 28-day mortality; (C) stepwise (forward) Cox regression analysis of variables predictive of 28-day mortality; only variables remaining significant after three steps of analysis are provided. AUC area under the curve, CI confidence interval, HR hazard ratio, NPV negative predictive value, PPV positive predictive value.