The utility of procalcitonin as a biomarker of hospital-acquired infection in severe COVID-19.

Abstract

Background: Hospital-acquired infection (HAI) in patients with COVID-19 admitted to the intensive care unit (ICU) is associated with increased mortality. The 'cytokine storm' associated with COVID-19 leads to extreme elevation of inflammatory biomarkers, including C-reactive protein (CRP). Procalcitonin (PCT) has been shown to be more discriminative than CRP in distinguishing HAI from other inflammatory processes.

Objectives: To investigate the utility of PCT in detecting HAI in patients with severe COVID-19.

Methods: Clinical and laboratory data from all patients admitted to a dedicated ICU with confirmed severe COVID-19 from 1 April 2020 to 31 August 2020 were prospectively captured. HAI was confirmed by serial PCT and CRP measurements, as well as microbiological data (positive microbiological cultures in clinical context). Data from patients who were on antibiotics on ICU admission, had a positive culture for a presumed pathogen during the first 48 hours of ICU admission, or already had suspected or proven HAI on admission were excluded. Optimal cut-offs with the highest sensitivity and specificity were determined. The discriminative power of PCT was assessed for each outcome, using receiver operating characteristic (ROC) analysis describing the area under the curve. Similarly, negative predictive values (NPVs) and positive predictive values (PPVs) were determined. The sensitivity and specificity for different PCT cut-off levels were calculated.

Results: Of 92 patients, 35 had confirmed HAI, which was significantly associated with mechanical ventilation (p<0.001) and mortality (p<0.001). ROC analysis demonstrated that a threshold PCT level of 0.22 μg/L resulted in 97% sensitivity and 40% specificity for predicting HAI. Similarly, sensitivity and specificity for CRP were 91.4% and 38.6%, respectively, when the CRP level was 133 mg/L. In patients with a PCT level <0.25 μg/L, the NPV was 92%, whereas for PCT levels >1.00 μg/L, the PPV was >50%. For PCT levels >40 μg/L, the PPV was 100%.

Conclusion: During HAI, PCT levels >1.00 μg/L had a moderate PPV of 52%, whereas levels <0.26 μg/L ruled out HAI with an NPV of 92%. With increased PCT values, the PPV rose to 100%, making it a better biomarker than CRP.

Study synopsis: What the study adds. During an episode of hospital-acquired infection (HAI) in patients with severe COVID-19, procalcitonin (PCT) levels >1.00 μg/L had a moderate positive predictive value (PPV) of 52%, whereas levels <0.26 μg/L had a negative predictive value (NPV) of 92% for proven HAI. For PCT levels >40 μg/L, the PPV was 100%.Implications of the findings. At levels <0.26 μg/L, PCT had an NPV >90%. This 'rule-out' characteristic of PCT may be especially valuable in scenarios of diagnostic equipoise with regard to the presence of bacterial co-infection. Clinicians should take care to not unjustifiably associate elevations in PCT levels with the presence of bacterial co-infection, unless levels are extremely high, in which case the PPV rises significantly.