W193 - Nasal Biomarker Testing to Rule out Viral Respiratory Infection and Triage Samples: A Test Performance Study

Abstract Text: The COVID-19 pandemic revealed an urgent need for practical screening tests to rule out respiratory infections for managing outbreaks and for routine screening in high-risk settings. PCR is the gold standard test for respiratory virus diagnosis but requires specialized equipment, is pathogen-specific, and may not be immediately available for an emerging virus. This study evaluated the performance of nasopharyngeal CXCL10, a host biomarker of diverse viral respiratory infections, as a virus-agnostic screening test to rule out viral respiratory infection. We also evaluated how viral prevalence and patient clinical features affect test performance.
We compared CXCL10 immunoassay to comprehensive respiratory virus PCR test results from 1088 nasopharyngeal samples. We used mathematical modeling to determine the negative predictive value (NPV) of CXCL10, and the prospective impact on patient triage and resource savings across varied viral prevalences, guided by real-world data from the COVID-19 pandemic. We used machine learning-based outlier analysis to explore clinical features associated with false negatives.
In our sample set, 32.6% of samples were virus-positive by PCR, and CXCL10 concentration accurately predicted virus positivity (A.U.C. 0.87, 95%CI 0.85-0.90). Model predicted that CXCL10 screening would enable a significant reduction in PCR testing, especially when viral prevalence is low (e.g., 92% of samples testing negative when viral prevalence is 5%). Outlier analysis identified features associated with false negatives including specific chemotherapeutic drugs and low viral load. These results demonstrate the utility of a nasopharyngeal biomarker to rule out respiratory infection, with potential applications in outbreak management and/or routine screening in high-risk settings.