Application of myxovirus resistance protein A in the etiological diagnosis of infections in adults

Abstract

Background: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A (MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of MxA to distinguish viral from bacterial infections.

Methods: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic (ROC) curve analysis were used to determine the diagnostic value of MxA, either alone or in combination with C-reactive protein (CRP) or procalcitonin (PCT), in patients with viral, bacterial, or co-infections.

Results: The value of MxA (ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections (82.3 [24.5-182.9] vs. 16.4 [10.8-26.5], P<0.0001) (82.3 [24.5-182.9] vs. 28.5 [10.2-106.8], P=0.0237). The area under the curve (AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799 (95% confidence interval [95% CI] 0.696-0.903), with a sensitivity of 68.9% (95% CI 54.3%-80.5%) and specificity of 90.0% (95% CI 74.4%-96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus (15.8 [9.6-47.6] ng/mL) and Epstein-Barr virus (12.9 [8.5-21.0] ng/mL) infections.

Conclusion: Our study showed the diagnostic efficacy of MxA in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, Epstein-Barr virus and human cytomegalovirus infections did not elicit elevated MxA expression.

Keywords: Biomarker; C-reactive protein; Myxovirus resistance protein A; Procalcitonin; Viral infections.

Figure 1

Participant flowchart.

Figure 2

The expression of MxA in the blood distinguishes between viral, bacterial, and viral-bacterial co-infections. A: the expression levels of MxA in viral (n=45), bacterial (n=30), and viral-bacterial co-infections (n=46) patients. The horizontal bars indicate the medians and interquartile ranges. P-values were calculated with the Kruskal-Wallis test and Dunn’s multiple comparisons test. B: ROC analysis of MxA for the differentiation of patients with viral and bacterial infections. C: ROC analysis of MxA for the differentiation of patients with viral and viral-bacterial co-infections. D: ROC analysis of MxA levels for the differentiation of patients with bacterial and viral-bacterial co-infections. MxA: myxovirus resistance protein A; ROC: receiver operating characteristic.

Figure 3

MxA combined with CRP or PCT can reliably distinguish between viral, bacterial, and viral-bacterial co-infections. A, B: MxA/CRP and MxA/PCT ratios in viral (n=45), bacterial (n=30), and viral-bacterial co-infections (n=46). The horizontal bars represent the medians and interquartile ranges. P-values were calculated with the Kruskal-Wallis test and Dunn’s multiple comparisons test. C: ROC analysis of MxA/CRP and MxA/PCT for the differentiation of patients with viral and bacterial infections. D: ROC analysis of CRP, PCT, and MxA levels; the combination of MxA and CRP levels; the combination of MxA and PCT levels; and the combination of MxA and CRP levels and PCT levels to distinguish patients with viral and bacterial infections. AUC: area under the curve; MxA: myxovirus resistance protein A; ROC: receiver operating characteristic; CRP: C-reactive protein; PCT: procalcitonin.

Figure 4

Expression of MxA in patients infected with different types of viruses. The bars indicate the median, and the horizontal bars represent the interquartile ranges. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; IAV: influenza A virus; IBV: influenza B virus; EBV: Epstein-Barr virus; HCMV: human cytomegalovirus; RSV: respiratory syncytial virus; MxA: myxovirus resistance protein A.