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

Abstract

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.

Keywords: COVID-19; LumiraDx antigen test; Rt-PCR; SARS-CoV-2; Sensitivity.

Fig. 1

LumiraDx SARS-CoV-2 antigen assay. Schematic representation (a), test strip (b), and instrument result screen (c). Images reproduced with permissions from LumiraDx, copyright 2020

Fig. 2

Roche cobas SARS-CoV-2 rt-PCR cycle threshold versus days since symptom onset. True positive (TP) and false negative (FN) results using the LumiraDx SARS-CoV-2 antigen test with nasal (NS) or nasopharyngeal (NP) swab specimens. Red circles and squares indicate participants positive by LumiraDx SARS-CoV-2 antigen test. Blue circles and squares indicate participants negative by LumiraDx SARS-CoV-2 antigen test. Dotted line represents Ct 33