Emergency Department point-of-care antiviral host response testing is accurate during periods of multiple respiratory virus co-circulation

FebriDx is a CE-marked, FDA-approved point-of-care test that detects the antiviral host response protein Myxovirus Resistance Protein A (MxA), in addition to C-reactive protein, using finger-prick blood. FebriDx MxA detection had a high negative predictive value for COVID-19 in symptomatic adults presenting to hospital in the first waves of the pandemic and was used subsequently as a 'rule out' triage tool in Emergency departments. The diagnostic accuracy of FebriDx MxA in the current context of co-circulation of influenza, SARS-CoV-2, and Respiratory Syncytial Virus (RSV), and in the era of COVID-19 vaccination, is unknown. We retrospectively evaluated the diagnostic performance of FebriDx MxA in adults with acute respiratory symptoms presenting to the Emergency Department (ED) of a large UK teaching hospital using Reverse Transcription Polymerase Chain Reaction (RT-PCR) as the reference standard (Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV). Between March 9th 2022 and March 8th 2023, 5426 patients had both FebriDx and RT-PCR testing with valid results. 999 (18.4%) of patients had influenza detected, 520 (9.6%) SARS-CoV-2, and 190 (3.5%) RSV. Negative Predictive Value (NPV) of MxA detection by FebriDx was 97.5% (96.9-98.0) for influenza, 97.1% (96.4-97.7) for SARS-CoV-2, 98.1% (97.5-98.6) for RSV, and 92.8% (91.8-93.7) for all viruses combined. In symptomatic adults, FebriDx MxA had a high NPV for influenza and RSV, and retained a high NPV for SARS-CoV-2, in the context of virus co-circulation and widespread COVID-19 vaccination. FebriDx continues to be a useful 'rule out' triage tool in the ED and could potentially be scaled to provide a national triage solution for future viral pandemics.