Abstract and Introduction
Abstract
Objectives: The LumiraDx SARS-CoV-2 Ag Test has previously been shown to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals symptomatic for coronavirus disease 2019 (COVID-19). This evaluation investigated the LumiraDx SARS-CoV-2 Ag Test as an aid in the diagnosis of SARS-CoV-2 infection in asymptomatic adults and children.
Methods: Asymptomatic individuals at high risk of COVID-19 infection were recruited in 5 point-of-care (POC) settings. Two paired anterior nasal swabs were collected from each participant, tested by using the LumiraDx SARS-CoV-2 Ag Test at the POC, and compared with results from reverse transcription–polymerase chain reaction (RT-PCR) assays (cobas 6800 [Roche Diagnostics] or TaqPath [Thermo Fisher Scientific]). We calculated positive percent agreement (PPA) and negative percent agreement (NPA), then stratified results on the basis of RT-PCR reference platform and cycle threshold.
Results: Of the 222 included study participants confirmed to be symptom-free for at least 2 weeks before testing, the PPA was 82.1% (95% confidence interval [CI], 64.4%-92.1%). The LumiraDx SARS-CoV-2 Ag Test correctly identified 95.8% (95% CI, 79.8%-99.3%) of the samples confirmed positive in fewer than 33 RT-PCR cycles and 100% (95% CI, 85.1%-100%) in fewer than 30 RT-PCR cycles while maintaining 100% NPA.
Conclusions: This rapid, high-sensitivity test can be used to screen asymptomatic patients for acute SARS-CoV-2 infection in clinic- and community-based settings.
Introduction
Only months after the identification of a novel virus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—and its associated disease—coronavirus disease 2019 (COVID-19)—tens of thousands of cases were reported in more than 100 countries.[1,2] The World Health Organization declared the SARS-CoV-2 outbreak a public health emergency of international concern in January 2020,[3] followed by the declaration of a pandemic on March 11, 2020.[4] One of the first major problems encountered in the evaluation and monitoring of the pandemic was the lack of diagnostic resources for COVID-19. In response, the Secretary of the US Department of Health and Human Services issued an Emergency Use Authorization (EUA) declaration in early February 2020 for the diagnosis of SARS-CoV-2.[5]
Accurate diagnosis is essential for identifying and managing SARS-CoV-2–infected patients and for the implementation of effective infection-control measures. Currently, the most sensitive testing method for the presence of SARS-CoV-2 is reverse transcription–polymerase chain reaction (RT-PCR) using nasopharyngeal swabs. This method has drawbacks for community-based asymptomatic screening, however, such as the requirement for laboratory testing and subsequent delays in reporting results to individuals, who may not isolate themselves until their result has been confirmed. Currently, high-sensitivity, rapid molecular tests for the identification of SARS-CoV-2 are available, but these tests are often difficult to deploy in community settings, such as drive-in hubs, schools, and workplaces. This difficulty is mainly because test cartridges require refrigeration, are not easily portable, can be difficult to connect directly to surveillance monitoring, and can be expensive to operate. Therefore, rapid molecular tests are not available for widespread use.[6] Affordable, easy-to-use, rapid (results in 10–30 minutes), and accurate diagnostic tests that can be used in local clinics at the point of care (POC) can help alleviate the burden that the COVID-19 pandemic has exerted on health care systems.[7] The US government called for the development of rapid POC SARS-CoV-2 antigen tests, which as of September 21, 2021, led to the US Food and Drug Administration (FDA) EUA of 34 rapid diagnostic tests that can be performed at the POC in any health care setting.[8,9] Variations in sensitivity and specificity have been reported, however, and many of the available SARS-CoV-2 rapid antigen tests have now been demonstrated to have a sensitivity below 80%, which means that there is a high chance that infected individuals could receive a false-negative test result.[10–15] When individuals receive a false-negative test result, these infected people, who may be asymptomatic, are not quarantined and thus contribute to the transmission of SARS-CoV-2.[16] This effect highlights the importance of evaluation studies to assess the sensitivity and specificity of each diagnostic test available on the market; these analyses can facilitate informed decision-making when selecting a test to use.
SARS-CoV-2 rapid antigen tests have been shown to have lower diagnostic sensitivity for samples obtained from asymptomatic people compared with symptomatic people.[13,15,17,18] Brümmer and colleagues[18] reported substantially lower accuracy for antigen tests in asymptomatic people (52.5%) compared with symptomatic people (76.7%), and the Abbott BinaxNOW rapid antigen test was reported to have a sensitivity of 35.8% in asymptomatic people compared with 64.2% in symptomatic people.[15] Because asymptomatic people have no means of identifying how long they have been infected or when they became infected because of the lack of symptoms, data review suggests that these tests have a wider RT-PCR cycle threshold (Ct) range and probably include people who are carrying remnant SARS-CoV-2 RNA rather than viable virus.[18] Brümmer and colleagues[18] estimated, based on 61 antigen tests, a range of Ct values from 20.5 to 27 for symptomatic patients and from 27.2 to 30.5 for asymptomatic atients. The lower sensitivity of lateral flow antigen tests indicates that these tests are better suited to testing symptomatic people in the early stages of infection.[18] To date, no POC SARS-CoV-2 rapid antigen test for professional use has received FDA EUA for use in asymptomatic people without required serial testing over 48 to 72 hours.[9] When an asymptomatic person in a congregate living setting has a high likelihood of SARS-CoV-2 infection and tests negative using a SARS-CoV-2 rapid antigen tests, a confirmatory test within 48 hours is recommended.[19]
The LumiraDx SARS-CoV-2 Ag Test is a microfluidic immunofluorescence POC assay for direct and qualitative detection of SARS-CoV-2–specific nucleocapsid protein antigen in nasal and nasopharyngeal swab specimens.[20,21] Recently, the LumiraDx SARS-CoV-2 Ag Test was evaluated for diagnosing acute COVID-19 in adults and children and was determined to detect 97.6% of COVID-19 infections compared with reference RT-PCR testing in symptomatic patients.[20] The test received initial FDA EUA for testing of symptomatic individuals suspected of having COVID-19 within 12 days of symptom onset and is designed to deliver test results in 12 minutes.[22] The current prospective study aimed to evaluate the performance of the LumiraDx SARS-CoV-2 Ag Test, which uses microfluidic technology, in asymptomatic adults and children.