Myxovirus resistance protein A to differentiate between viral and non-viral respiratory infections in adults: a prospective study

Objectives: To assess the diagnostic utility of Myxovirus resistance protein A (MxA) in differentiating between viral and non-viral respiratory infections in adults. Methods: This prospective, multicenter diagnostic accuracy study enrolled adults with acute respiratory infections (ARI) from outpatient and inpatient settings, alongside asymptomatic controls. Peripheral blood was collected for quantitative MxA measurement. Pathogen detection used targeted next-generation sequencing combined with conventional microbiological testing. Aetiological diagnoses were determined using standardized algorithms based on detected pathogens. The diagnostic accuracy of MxA for identifying viral ARIs was calculated. Results: Among 518 ARI patients, 325 had viral pathogens detected, 131 had bacterial/fungal pathogens, and 62 had no pathogen detected. Median MxA levels were significantly higher in viral (123.6 ng/ml; interquartile range [IQR], 56.4–189.6) than bacterial/fungal infections (15.9 ng/ml; IQR, 9.9–38.1; Bonferroni test p < 0.001) and controls (n = 158; 8.2 ng/mL; IQR, <5.0–16.4; Bonferroni test p < .001). The area under the receiver operating characteristic curve (AUC) for differentiating viral from bacterial/fungal infections was 0.83 (95% confidence interval [CI], 0.79–0.87). At an optimal cutoff of 50 ng/ml, MxA yielded a sensitivity of 77.8% (95% CI, 73.3–82.4%) and a specificity of 80.2% (95% CI, 73.3–87.0%). MxA levels were also elevated in atypical bacterial infections (n = 22; 60.9 ng/mL; IQR, 23.4–114.8), with no significant difference from viral group (Bonferroni test p = 0.12). When atypical bacteria were excluded, the AUC for differentiating viral from non-viral infections was 0.80 (95% CI, 0.76–0.84). Conclusions: MxA demonstrates high diagnostic accuracy in distinguishing between viral and non-viral respiratory infections in adults.