Characterization of CXCL10 as a biomarker of respiratory tract infections detectable by open-source lateral flow immunoassay

ABSTRACT Understanding core mechanisms common to respiratory tract viral pathogenesis and host-responses to infections may provide biomarkers for at-risk patient populations that guide interventions aimed at reducing morbidity, mortality, and economic costs. Secreted interferon stimulated gene protein products including CXCL10, CXCL11, and TNFSF10 could provide early biomarker signals that are prognostic for respiratory tract viral infections. In the present study, we had the overarching goal of defining the expression patterns of CXCL10, CXCL11, and TNFSF10 in clinical respiratory mucosal samples for multiple respiratory tract infections including respiratory syncytial virus, rhinovirus, influenza A and SARS-CoV-2 to inform the development of a host-biomarker point of care lateral flow immunoassay tool. Gene expression levels from upper airway samples suggested that CXCL10 and CXCL11 elevations were consistent across multiple viruses, correlated with higher SARS-CoV-2 viral load, and had a lower variance over the course of COVID-19 infection compared to TNFSF10 . Deep proteomic profiling using mass-spectrometry revealed CXCL10 protein was not detectable in oral samples from healthy individuals. CXCL10 levels were measured from the saliva of SARS-CoV-2 infected individuals and showed significant elevations in CXCL10 protein concentration. A prototype lateral flow immunoassay for detecting CXCL10 protein with a sensitivity of 2ng/mL in human saliva is presented. Our work provides a foundation for further exploration of CXCL10 as a host biomarker relevant in respiratory tract viral infections. Leveraging lateral flow immunoassay technology for detection of biomarkers prognostic of respiratory tract infection may provide opportunities to intervene selectively and aggressively in those most at risk of poor outcomes.