Validation of CXCL10 as a biomarker of respiratory tract infections detectable by lateral flow immunoassay

Introduction: Biomarkers of respiratory tract infections historically focused on the etiological cause of infection, although much of the morbidity and mortality is driven by the host-pathological response. Aim: Determine host biomarkers indicative of viral respiratory tract infections that are amenable to lateral flow immunoassay (LFIA) testing. Methods: Datamining was performed on in-house and publicly available datasets from respiratory syncytial virus (RSV), rhinovirus, influenza A and SARS-CoV-2 infected patient nasopharyngeal swab samples and compared to healthy controls. CXCL10, CXCL11 and TNFSF10 gene expression levels were assessed and a correlation analysis was performed in relation to infection severity and time-course. Lastly, the signature was validated at the protein level in saliva as a prerequisite for development of a host-response LFIA. Results:CXCL10 and CXCL11 upregulation was positively correlated with RSV when compared to control (p= 0.016, p= 0.006). No significant association was found with influenza A or rhinovirus for all three genes. CXCL10/CXCL11/TNFSF10 upregulation was positively correlated with SARS-CoV-2 infection when compared to control (p < 0.001). CXCL10 expression correlated with COVID-19 severity and had the lowest variance over infection time-course. CXCL10 was not detected at the protein level in healthy saliva but was elevated in saliva from COVID-19 patients. A CXCL10 LFIA was developed with a sensitivity of 2 ng/ml in a buffer and artificial saliva. Conclusion: The findings validate the potential utility of examining host immune responses during viral respiratory tract infections by exploring CXCL10 as a biomarker detectable by LFIA.