Antiviral Response in the Nasopharynx Identifies Patients with Respiratory Virus Infection

Abstract
Background: Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms.

Methods: We performed RNASeq on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample.

Results: Our first study showed that a signature of three mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% C.I. 0.9-1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall AUCs were: CXCL11 AUC=0.901 (95% CI 0.86-0.94); CXCL10 AUC=0.85 (95%CI 0.80-0.91). Patients were primarily older adults or young children, reflecting the population tested for respiratory viruses in our healthcare system.

Conclusions: Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.

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