Analysis of proinflammatory cytokine levels and other biomarkers
IL-6 was significantly higher in patients with SBI than in those with VI or NPI [median (IQR) pg/ml: 163 (70.4-459.5) vs 0.7 (0.7-0.7) vs 0.7 (0.7-0.7), respectively; p < 0.001], being undetectable in all controls. To note, the patient with the highest level of IL-6 was the case of confirmed bacterial pneumonia (733 pg/ml). However, in the patient with the bacterial-viral coinfection, IL-6 was undetectable. Figure 2 represents the values of IL-6 and other significant biomarkers (neutrophils, CRP and PCT) of the study subgroups, including the optimal cut-off point for each parameter calculated by the Youden index. IL-12p70 was not detected in any of the cases or controls. The rest of the cytokines analyzed (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-17a, TNFα, IFN-γ) did not show any significant difference between cases and controls or among different groups of cases. No differences were found in any of the cytokines analyzed between the cases diagnosed with VOC and the rest of the patients. None of the cytokine levels significantly correlated with possible confounders as the age or the number of previous admissions.
The AUC of IL-6 to discriminate confirmed SBI was 0.87 (95% CI 0.77-0.93), similarly to the other significant parameters [neutrophils 0.87 (0.78-0.94); CRP 0.89 (0.81-0.96); procalcitonin 0.84 (0.73-0.91)]. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL. Data of sensibility, specificity, PPV and NPV (the last two according to various possible PR of SBI) of IL-6 and other significant biomarkers are represented in Table 4. IL-6 had very high values of PPV and NPV, NPV values being similar to other biomarkers, with significantly higher PPV values (PPV of 100% for a PR of 5, 10 and 15%; NPV of 98.7%, 97.3% and 95.8% for a PR of 5, 10 and 15%, respectively).