A Rapid, High-Sensitivity SARS-CoV-2 Nucleocapsid Immunoassay to Aid Diagnosis of Acute COVID-19 at the Point of Care: A Clinical Performance Study

Drain, Paul K.; Ampajwala, Madhavi; Chappel, Christopher; Gvozden, Andre B.; Hoppers, Melanie; Wang, Melody; Rosen, Robert; Young, Stephen; Zissman, Edward; Montano, Michalina

INTRODUCTION: The LumiraDx severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test, which uses a high-sensitivity, microfluidic immunoassay to detect the nucleocapsid protein of SARS-CoV-2, was evaluated for diagnosing acute coronavirus disease 2019 (COVID-19) in adults and children across point-of-care settings (NCT04557046). METHODS: Two paired anterior nasal swabs or two paired nasopharyngeal swabs were collected from each participant. Swabs were tested by the LumiraDx SARS-CoV-2 antigen test and compared with real-time polymerase chain reaction (rt-PCR; Roche cobas 6800 platform). Sensitivity, specificity and likelihood ratios were calculated. Results were stratified on the basis of gender, age, duration of symptoms, and rt-PCR cycle threshold. RESULTS: Out of the 512 participants, aged 0–90 years, of this prospective validation study, 414 (81%) were symptomatic for COVID-19 and 123 (24%) swabs were positive for SARS-CoV-2 based on rt-PCR testing. Compared with rt-PCR, the 12-min nasal swab test had 97.6% sensitivity and 96.6% specificity, and nasopharyngeal swab had 97.5% sensitivity and 97.7% specificity, within 12 days of symptom onset, representing the period of infectivity. All (100%) samples detected within 33 rt-PCR cycles were also identified using the antigen test. Results were consistent across age and gender. The user error rate of the test system when used by minimally trained operators was 0.7% (95% confidence interval [CI] 0.1–3.7%). CONCLUSION: The rapid, high-sensitivity assay using nasopharyngeal or anterior nasal sampling may offer significant improvements for diagnosing acute SARS-CoV-2 infection in clinic- and community-based settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-021-00413-x.