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

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Improved and optimized drug repurposing for the SARS-CoV-2 pandemic.

The active global SARS-CoV-2 pandemic caused more than 426 million cases and 5.8 million deaths worldwide. The development of completely new drugs for such a novel disease is a challenging, time intensive process. Despite researchers around the world working on this task, no effective treatments have been developed yet. This emphasizes the importance of drug repurposing, where treatments are found among existing drugs that are meant for different diseases. A common approach to this is based on knowledge graphs, that condense relationships between entities like drugs, diseases and genes. Graph neural networks (GNNs) can then be used for the task at hand by predicting links in such knowledge graphs. Expanding on state-of-the-art GNN research, Doshi et al. recently developed the Dr-COVID model. We further extend their work using additional output interpretation strategies. The best aggregation strategy derives a top-100 ranking of 8,070 candidate drugs, 32 of which are currently being tested in COVID-19-related clinical trials. Moreover, we present an alternative application for the model, the generation of additional candidates based on a given pre-selection of drug candidates using collaborative filtering. In addition, we improved the implementation of the Dr-COVID model by significantly shortening the inference and pre-processing time by exploiting data-parallelism. As drug repurposing is a task that requires high computation and memory resources, we further accelerate the post-processing phase using a new emerging hardware-we propose a new approach to leverage the use of high-capacity Non-Volatile Memory for aggregate drug ranking.

FebriDx host response point-of-care testing improves patient triage for coronavirus disease 2019 (COVID-19) in the emergency department.

OBJECTIVES: Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED). DESIGN: We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm. SETTING: Emergency department of a university teaching hospital. PATIENTS: Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a 'high-risk' area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area. RESULTS: Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34-92) for FebriDx-negative patients and 203 minutes (IQR, 142-255) for FebriDx-positive patients (difference of -134 minutes; 95% CI, -144 to -122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%-97%). CONCLUSIONS: FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2-positive patients.