SARS-CoV-2 Antigen Testing Is Here but Is It Really a ‘Game Changer’  

First came the molecular and then the serological assays. And now a third kind of coronavirus testing methodology has made its official US debut: antigen tests. Some have hailed this development as a “game changer” in the effort to meet the current unprecedented demand for testing. But are they right?

The Diagnostic Challenge

Molecular tests using reverse transcription-polymerase chain reaction (PCR) to detect RNA material from the virus is accurate but slow to the extent it must be performed at an offsite laboratory. In addition to being much faster, blood-based serology tests detecting antibodies produced by the body to fight the SARS-CoV-2 virus offer the potential to differentiate between active and previous infection. But serology tests lack the specificity and sensitivity of PCR assays making them prone to generate false positives and negatives.

Like antibody testing, antigen tests detect viruses indirectly. But there are some important differences. For one thing, while antibody tests are blood based, antigen tests analyze tissue nasopharyngeal samples collected by a swab the way PCR tests do. And instead of antibodies, antigen tests detect the presence of antigens or toxins a virus produces that cause the body to produce those antibodies.

The downside is that antigen tests are less sensitive than PCR assays, which makes them prone to false negatives. Accordingly, patients who test negative may need to have confirmatory PCR tests. However, antigen testing may still be appropriate for many applications like screening health care workers and other high-risk groups and triaging patients during peak outbreak periods.

The Promise of SARS-CoV-2 Antigen Testing

In the context of the COVID-19 situation, antigen testing offers significant advantages over the other available methods. Antigen tests are relatively inexpensive to produce and generate results rapidly at the point of care. This combination of scalability and speed makes antigen testing the potential solution to the urgent need for high throughput testing essential to contain the spread of COVID-19 and ensure the safe re-emergence of the economy.

 “Antigen tests are important in the overall response against COVID-19 as they can generally be produced at a lower cost than PCR tests,” noted US Food and Drug Administration (FDA) Commissioner Stephen Hahn. “And once multiple manufacturers enter the market, antigen tests can potentially scale to test millions of Americans per day due to their simpler design, helping our country better identify infection rates closer to real time.”

FDA Approves First Antigen Test for SARS-CoV-2

On May 8 the FDA for the first time granted Emergency Use Authorization (EUA) to an antigen coronavirus test. The Quidel Sofia 2 SARS Antigen FIA assay is a point of care test designed for use with the firm’s Sofia 2 fluorescent immunoassay analyzer to detect SARS-CoV-2 protein fragments in nasal or nasopharyngeal samples. It has a reported sensitivity of 85 percent, a rate that definitely puts false negatives into play. The agency reportedly cleared the test within 24 hours of receiving Quidel’s application.

It is not surprising that Quidel is the first to bring a SARS-CoV-2 antigen test to the US market. The firm also produces immunoassays for its Sofia platform including tests for influenza A and B, respiratory syncytial virus (RSV), group A Streptococcus and other infectious diseases. Quidel claims that the new Sofia 2 SARS Antigen FIA test, which the EUA authorizes moderate- and high-complexity CLIA laboratories and facilities that have a CLIA waiver to perform, delivers results in 15 minutes and costs only $5 per test to produce.

Potential Impact

The headline is not just that a SARS-CoV-2 antigen test has reached the market but the potential impact of the test to help close the current gap between COVID-19 testing demand and supply. Quidel says that it is ramping up production from 200,000 to 1.5 million tests per week and expects in the next few weeks to have the capacity to make 9 million tests per months. And because 40,000 doctors’ offices across the country already have a Sofia analyzer installed in their office, the test should be more readily accessible than most of the other assays that have secured EUA status.

And more may be on the way. The FDA said that it is expecting to clear more SARS-CoV-2 antigen tests and that it intends to create a new streamlined and expedited EUA pathway for antigen tests.

Takeaway

PCR testing is the gold standard for COVID-19 testing accuracy but it is not a high-throughput modality and thus not enough to meet the current unprecedented test volume demands. Antigen testing is scalable but lacks the sensitivity necessary to make negative test results completely reliable. It is for this reason that several models of rapid influenza diagnostic tests (RIDTs) had to be pulled off the market. Even so, just the way RIDTs are in demand during a bad flu season, SARS-CoV-2 antigen tests may represent an acceptable better-than-nothing alternative in a market facing the dire need for COVID-19 testing supply. Thus, while not yet a “game changer,” the introduction of antigen testing should help satisfy the desperate demand for coronavirus testing.