A Novel Host-Based Assay Distinguishes between Simple Influenza Patients and Influenza Patients with Bacterial Coinfection

Background: Differentiating bacterial from viral infection in the clinical setting is a challenge often faced by physicians, impacting patient management. This difficulty often leads to antibiotic misuse. ImmunoXpert™ is a novel host-based assay integrating three proteins: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10) and C-reactive protein (CRP). In this analysis we aimed to examine the performance of the host-based assay in pediatric patients with Influenza infection.

Methods: The study population included pediatric patients enrolled at the pediatric emergency department and pediatric ward of a secondary medical center in Israel. Patients had a confirmed Influenza A infection according to a nasal swab real time PCR and were also tested with the host-response assay during the winter seasons of 2017/2018 and 2018/2019. Patient etiology (bacterial or viral) was determined by unanimous agreement of a three senior pediatrician panel, based on clinical, laboratory and radiological data. Experts were blinded to the assay result. The assay gives one of three outcomes: bacterial (including bacterial-viral coinfection), viral or equivocal. Expert panel diagnosis was compared with assay outcome.

Finidings: Sixty-one children aged 0-17 years (mean 4.75 years), 60% female, had a PCR-confirmed Influenza A infection and ImmunoXpert™ test result. Of these, 2 were labeled as bacterial, 48 as viral and 11 were indeterminate. The assay demonstrated sensitivity of 100% (95% CI: 15.81%-100%), specificity of 86.96% (95% CI: 73.74%-95.06%) and negative predictive value of 100% (95% CI: 100%-100%); equivocal result rate was 5%.

Conclusion: ImmunXpert™ exhibited high diagnostic performance for distinguishing simple viral from viral-bacterial coinfection in influenza positive pediatric patients. Large-scale prospective cohort studies are warranted to support the assay’s potential to improve antimicrobial treatment decisions.