New Evidence Supports Suitability of Antigen Testing for COVID-19 Screening

Not perfect, but good enough. That is the basic theory for using rapid antigen tests for COVID-19 surveillance even though they are less accurate than molecular assays in detecting the SARS-CoV-2 virus. A new research study published in the Journal of Infectious Diseases offers important evidence supporting that theory. Specifically, it suggests that performing antigen tests more frequently can raise their sensitivity commensurate with the sensitivity levels of PCR tests performed at longer intervals.

The Diagnostic Challenge

Molecular tests using reverse transcription-polymerase chain reaction (RT PCR) to detect RNA material from the SARS-CoV-2 virus performed at an offsite laboratory represent the gold standard for accurate coronavirus detection. The problem is that these tests are too costly and slow to meet the need for rapid screening.

The cost-effectiveness and speed of tests that identify the presence of antigens or toxins a virus produces that cause the body to produce antibodies are far more suited for rapid testing of the asymptomatic at the point of care. However, antigen tests lack the sensitivity of molecular assays. This creates the risk of false negatives and need for confirmatory testing. However, while antigen testing is not appropriate for diagnostic and treatment uses, they are sensitive enough for screening the asymptomatic or only mildly symptomatic for purposes of surveillance and infection control.

That, at least, is the contention of test producers, laboratories, policy makers and others that have carved out a stake in antigen testing. However, because the SARS-CoV-2 virus emerged without warning, there has been precious little time and opportunity to gather the scientific evidence needed to prove that those contentions are true.

 The University of Illinois Study

Published on June 30, 2021, the new study is the work of a team of researchers from the University of Illinois at Urbana-Champaign that set out to evaluate the performance of rapid antigen and molecular SARS-CoV-2 tests over the course of mild and asymptomatic infections. They analyzed samples collected via the University’s protocol requiring on-campus students and staff to undergo saliva-based SARS-CoV-2 molecular testing every two to four days.

The researchers formed a subset of 43 individuals who tested positive for COVID-19 and asked them to submit daily saliva and nasal swab samples over the course of 14 days. They then performed saliva- and swab-based PCR testing on the samples, as well as swab-based rapid antigen testing using Quidel’s Sofia SARS Antigen FIA test run on the Sofia 2 device. The researchers also performed viral culture of the nasal samples to determine at what points throughout the 14 days of testing the patients were likely to have been infectious.

The Study’s Finding

Predictably, the researchers found that PCR testing had higher sensitivity than antigen testing—roughly 98 percent for saliva- and swab-based PCR tests versus 80 percent for antigen testing. However, they also found that they could compensate for this difference by performing the antigen tests more frequently. Thus, antigen testing subjects every three days raised antigen assay sensitivity to better than 98 percent, the equivalent sensitivity of molecular assays during testing once a week.

In addition, researchers found that PCR testing continued to flag samples as positive even after the viral cultures were no longer positive. This finding bolsters the argument made by some advocates of antigen testing that the high sensitivity of PCR tests may actually be a disadvantage in the screening context to the extent that it makes those assays more apt to return positive test results for patients who are no longer infectious and thus not a threat to spread COVID-19. By contrast, positive antigen tests offer a more reliable indication that the test subject is infectious at the time of testing.

Takeaway

Until now, the suitability of using antigen testing for COVID-19 screening has been taken largely on faith. The University of Illinois study is significant because it is among the first research projects providing scientific evidence to support this case.

“In general, serial antigen screening will be as effective as PCR in catching and assessing infectiousness,” noted Bruce Tromberg, leader of the NIH Rapid Acceleration of Diagnostics Tech program, which provided funding for the study. He noted that the minimum cadence for effective antigen testing should be two times per week, with three times a week best for regular screening of people in high-prevalence areas or engaged in higher-risk activities.