OBJECTIVES: While the Infectious Disease Society of America recommends molecular testing for symptomatic patients suspected of having COVID-19, antigen testing is still frequently used. This may result in missed opportunities for appropriate diagnosis and treatment or management of common viruses, including SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), particularly relative to point-of-care multiplex molecular tests such as Xpert® Xpress CoV-2/Flu/RSV (“Xpert”). The aim of this study was to assess potential missed opportunities for diagnosis of SARS-CoV-2, influenza, and RSV in the United States between October 2022 – November 2023 with antigen tests compared to Xpert.

METHODS: A decision tree model was constructed to compare testing with Xpert versus antigen testing for SARS-CoV-2 with or without influenza in terms of the number needed to test (NNT) to detect one additional true positive result. Test positivity data was drawn from the National Respiratory and Enteric Virus Surveillance System and was aggregated at the monthly level based on Centers for Disease Control Morbidity and Mortality Weekly Report week start dates.

RESULTS: Compared SARS-CoV-2 antigen testing, the NNT with Xpert to yield one additional true positive detection of SARS-CoV-2, influenza, or RSV ranged from three to 39. Compared to antigen testing for SARS-CoV-2 and influenza, NNT ranged from five to 54. NNT was lowest in November 2022 and highest in July 2023.

CONCLUSIONS: During the height of the 2022-2023 respiratory season, an additional true positive detection of SARS-CoV-2, influenza, or RSV could have been identified by testing as few as three patients with Xpert rather than by antigen for SARS-CoV-2 alone. Patients with knowledge of their true disease status may be more likely to receive disease-appropriate treatment and to quarantine, reducing the risk of morbidity and mortality both to the patient and due to onward transmission.