Host gene expression in the Nasopharynx can discriminate microbiologically confirmed viral and bacterial lower respiratory tract infection.

Introduction: Distinguishing viral versus bacterial lower respiratory tract infection (LRTI) is challenging. We previously developed a rapid, host response-based test (Biomeme HR-B/V assay) using peripheral blood samples to identify viral versus bacterial infection. We assessed the performance of this assay when using nasopharyngeal (NP) samples. Methods: Patients with LRTI were enrolled, and a NP swab sample was run using the HR-B/V assay (assessing 24 gene targets) on the Franklin Results: Nineteen patients (median age 62 years, 52.1% male) were included. When using the prior HR-B/V classifier on NP samples of 19 patients with LRTI (12 viral, 7 bacterial), the area under the receiver operator curve (AUC) for viral versus bacterial infection was 0.786 (0.524-1), with accuracy 0.79 (95% CI 0.57-0.91), positive percent agreement (PPA) 0.43 (95% CI 0.16-0.75), and negative percent agreement (NPA) 1.00 (95% CI 0.76-1). The novel model had AUC 0.881 (95% CI 0.726-1), accuracy 0.84 (95% CI 0.62-0.94), PPA 0.86 (95% CI 0.49-0.97), and NPA 0.83 (95% CI 0.55-0.95) for bacterial infection. Validation in two external datasets showed AUC of 0.932 (95% CI 0.90-0.96) and 0.915 (95% CI 0.88-0.95). Conclusions: We show that host response in the nasopharynx can distinguish viral versus bacterial LRTI. These findings need to be replicated in larger cohorts with diverse LRTI etiologies.