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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: For any human sample analysis the Hamilton Integrated Research Ethics Board (HiREB) provided review and approval of the study. Procurement of nasopharyngeal swab (NPS) and saliva samples from consented study subjects was approved under HiREB protocols 4914T, 5099T, and 10771. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Table 1 provides details on the publicly available datasets that were used including URLs, gene expression method used, and notes on the samples from the datasets. Supplementary Table 1 provides information on the publicly available datasets that were retrieved from Harmonizome. In-house gene expression data analyzed with Clariom D microarray technology will be deposited to GEO upon acceptance with appropriate URL, accession numbers, and DOIs provided.