NEW YORK – A team led by researchers at the University of Illinois at Urbana-Champaign have evaluated the performance of rapid antigen and molecular SARS-CoV-2 tests over the course of mild and asymptomatic infections.
Their findings, published this week in the Journal of Infectious Diseases, indicate that when used in serial fashion, both rapid antigen and molecular assays are effective for COVID-19 screening, though certain advantages and disadvantages distinguish the two types of tests.
The study looked at samples collected from 43 individuals at the University of Illinois, where on-campus students and staff are required to undergo saliva-based SARS-CoV-2 molecular testing every two to four days. A subset of individuals who tested positive for COVID-19 based on this testing were enrolled in the study and submitted daily saliva and nasal swab samples for 14 days. Using those samples, the researchers ran saliva- and swab-based PCR testing as well as swab-based rapid antigen testing using Quidel's Sofia SARS Antigen FIA test and 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 patients were likely infectious.
The study found that while PCR testing had higher sensitivity than antigen testing (roughly 98 percent for both saliva- and swab-based PCR tests versus 80 percent for antigen testing), more frequent testing with antigen assays compensated for this difference. Testing using antigen tests every three days raised antigen assay sensitivity to better than 98 percent, the equivalent sensitivity of weekly testing using the molecular assays.
These findings bolster the argument for using frequent antigen testing to control the spread of SARS-CoV-2. Prominent epidemiologists and others have argued for such an approach since the early days of the pandemic but there has been little real world data (as opposed to modeling experiments) evaluating the effectiveness of such a strategy.
The researchers also found that PCR testing continued to flag samples as positive even after the viral cultures were no longer positive, suggesting that they may be returning positive test results for patients who are no longer infectious. Proponents of antigen testing have often argued that PCR's high sensitivity is a downside in this respect as it is picking up people who are not a threat to spread the disease, whereas antigen testing is better targeted to the period of time when a person is actually infectious. The JID findings are consistent with that argument.
"In general, serial antigen screening will be as effective as PCR in catching and assessing infectiousness," said Bruce Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering and 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.
Tromberg added, though, that antigen tests are not likely to be effective for detecting breakthrough infections in vaccinated people, given that peak viral loads in such patients may never reach the levels of detection of most antigen tests.
He suggested that in this population serial antigen tests are perhaps better than nothing, but that PCR is recommended "for vaccinated people to assess breakthrough infections."