Rapid antigen testing study by ARUP and U of U Health

February 3, 2021

Point-of-care antigen testing with the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW) is not as sensitive as standard nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2, the virus that causes COVID-19, in asymptomatic college students, according to a new study conducted by ARUP Laboratories and University of Utah Health.

“This is one of the largest studies to evaluate the performance of a rapid SARS-CoV-2 antigen test in an exclusively asymptomatic population,” said Kimberly Hanson, MD, MHS, section chief of Clinical Microbiology and medical director of Mycology at ARUP, and head of the Immunocompromised Host Infectious Diseases Service at the University of Utah Hospital and Huntsman Cancer Center. “Several SARS-CoV-2 antigen tests have received FDA Emergency Use Authorization, but they are currently labeled for use in symptomatic patients, typically within the first 7 days from symptom onset.”

NAATs, although very sensitive for SARS-CoV-2, are also expensive and may take longer than antigen tests. Antigen tests are cheaper, faster, and better suited to self-administered testing, attributes that make them attractive for use as a screening tool in asymptomatic individuals.

“Clinical studies have shown variable positive percent agreement between some rapid antigen tests and NAATs in symptomatic individuals,” said Lauren Pearson, DO, MPH, ARUP Clinical Laboratory Improvement Amendments (CLIA) laboratory director for University of Utah Health and the Huntsman Cancer Institute. “But studies on the performance of these tests in asymptomatic or presymptomatic individuals—who may be able to transmit the virus—are limited. We wanted to assess whether these tests might be appropriate for off-label use in asymptomatic population screening.”

The study found that in 2,645 asymptomatic college students who presented for random screening, there was 53.3% positive agreement between the antigen test and a standard NAAT (a reverse-transcription polymerase chain reaction [RT-PCR] assay) for SARS-CoV-2. Specifically, the antigen test identified 24 of the 46 individuals who were found to have SARS-CoV-2 using the NAAT.

“Our results are consistent with the results of other research,” Pearson said. “Studies that included both symptomatic and asymptomatic individuals have found that point-of-care antigen tests are substantially less sensitive than NAATs.”

The study also found that the positive agreement rate was greater in individuals with a presumably higher viral load (as suggested by a lower cycle threshold, or Ct, for the NAAT); 95.8% positive agreement was observed at a Ct of <23.0.

“It’s important to note, however, that Ct values are not a truly quantitative measure of virus load. In addition, these values are not comparable across PCR platforms and should not be used to infer whether or not a patient is infectious to others,” Hanson said.

Although the FDA has warned that rapid antigen tests can give false-positive results, the study found that BinaxNOW was very specific for SARS-CoV-2 in this setting, with no false positives.

“These observations raise the question of whether confirmation of positive BinaxNOW results is necessary, as long as there is strong quality control and the individuals performing the test are well trained. This is especially important in the context of at-home testing. Additional studies are needed to determine whether BinaxNOW test performance will be comparable in a telehealth-observed home setting,” Pearson said.

The results have important implications for the use of point-of-care antigen testing as a screening tool. Timely identification and isolation of infected individuals, in conjunction with other measures such as physical distancing, face masking, and proper hand hygiene, are crucial to prevent the spread of SARS-CoV-2. Because individuals may be infectious before becoming symptomatic or in the absence of symptoms, screening tests must be able to identify SARS-CoV-2 in asymptomatic patients.

“Caution is warranted when using point-of-care antigen testing for screening asymptomatic individuals, even though it may be useful in resource-limited settings,” Pearson said. “The potential implications of a false-negative antigen result depend on the setting and patient population to which the test is applied. As of right now, NAAT remains the standard for the diagnosis of SARS-CoV-2 infection.”

A false-negative test result may occur for a variety of reasons, including sampling error, the presence of inhibitors in the sample, or errors in the performance of the test.

“Careful assessment of the impact of false-negative results is needed before a testing strategy utilizing antigen tests is implemented,” Hanson said. “No test is perfect. The key is to know the test being used and its performance characteristics in your clinical setting.”

Rebecca Parker, Medical Writer and Editor