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

TL;DR

This study shows that gene expression in the nasopharynx can help distinguish between viral and bacterial lower respiratory tract infections.

Contribution

The novel predictive model using nasopharyngeal gene expression improves accuracy in identifying viral versus bacterial infections.

Findings

The novel model achieved an AUC of 0.881 for bacterial infection detection in NP samples.

Validation in external datasets showed AUCs of 0.932 and 0.915 for bacterial infection detection.

Host response in the nasopharynx can effectively distinguish viral from bacterial LRTI.

Abstract

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.

Patients with LRTI were enrolled, and a NP swab sample was run using the HR-B/V assay (assessing 24 gene targets) on the FranklinTM platform. The performance of the prior classifier at identifying viral versus bacterial infection was assessed. A novel predictive model was generated for NP samples using the same 24 targets. Results were validated using external datasets with nasal/NP RNA sequence data.

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).

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.

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