Advancing Respiratory Virus Diagnostics: Integrating the Nasal IFN-I Score for Improved Viral Detection

Background: This study aimed to demonstrate the utility of the nasal Type I interferon (IFN-I) response as a marker for respiratory viral infections (RVIs) and its potential to enhance diagnosis when combined with first-line PCR tests for Influenza A/B, RSV, and SARS-CoV-2.

Methods: Nasopharyngeal swabs (NPS) from patients at Hospices Civils de Lyon (November 2022-April 2024) suspected of viral infections (n = 788) and from healthy controls (n = 53) were analysed. The IFN-I score was measured using the FILMARRAY® IFN-I pouch prototype, which detects four interferon-stimulated genes. The study evaluated the performance of the IFN-I score in detecting samples positive for viruses by first-line PCR and assessed its benefit in diagnosing RVIs in samples initially classified as negative by PCR.

Findings: Out of 788 NPS included, 504 (64%) were positive with the first-line PCR tests, and IFN-I score was significantly higher in those samples (median [IQR]: 13.00 [2.76-45.40]) compared to ones collected from healthy controls (1.09 [0.67-1.30]; p < 0.0001), with an area under the curve (AUC; 95% CI) of 0.92 (0.90-0.92). Moreover, out of the 284 NPS negative with first-line PCR tests, suspicion of viral infection according to IFN-I score was found in 63% of cases (178/284). Second-line test (BioFire® Respiratory Panel 2.1 plus) and viral metagenomic confirmed the presence of viruses 94% of cases.

Interpretation: The study highlights the potential of integrating nasal IFN-I score into clinical workflows to improve RVI diagnosis and enhance preparedness for emerging viruses.

Funding: Public grant overseen by the French National Research Agency (ANR21-RHUS-08/ANR-23-CHIN-0001).