RAT effectiveness: does it wane with each new COVID-19 variant?

Rapid Antigen Tests – or RATs – are probably as effective as they’ve ever been, even when it comes to new COVID-19 variants.

That’s because these tests seek out parts of the virus that aren’t inclined to change.

While the spike protein on the SARS-CoV-2 virus is the site of most immunity-evading mutations, RATs instead search for the nucleocapsid proteins below the virus surface.

The nucleocapsid – or N protein – is where the virus’s genetic material is contained.

A chemical reaction between this protein and the solution used to perform the test is what generates a positive marker on the RAT cassette.

Rapid antigen testing provides a quicker testing option to the more accurate polymerase chain reaction (PCR) tests that are conducted in labs, but the sacrifice is precision.

During the early stages of the Omicron outbreak, Cochrane, a global health not-for-profit based in the UK, found antigen testing accurately correctly identified an average of 73% of symptomatic positive cases, and just 55% of asymptomatic cases.

Right now, the Therapeutic Goods Administration (TGA) is reviewing the performance of all “COVID-19-specific” tests. That includes lab-based PCR testing and all rapid antigen tests.

The review is being undertaken “as quickly as possible” in conjunction with the Doherty Institute and national Serology Reference Laboratory. In its announcement, the TGA noted that “[Test] manufacturers are required to undertake proactive monitoring to ensure their tests are not impacted by the variants of the virus.”


More on RAT effectiveness: How do Rapid Antigen Tests work, and are we using them wrong


Professor Deborah Williamson is a clinical biologist at the Doherty Institute, which is helping run the evaluations for the TGA.

So far, only one RAT – a CovClear product – has failed to meet the TGA’s minimum standard, and only when identifying wild type and Delta strains (it passed the Omicron identification threshold). Over 70 product evaluations are yet to be reported.

Williamson explains that even though these evaluations are highly systematic and specialised, they are lab-based. What they can’t account for is the biology of the person undertaking the test, which also influences how a person sheds a virus.

Prior vaccination can also alter viral shedding patterns.

“The nucleocapsid protein is under less selection pressure than the spike protein, so we see far fewer mutations [there], and certainly all the work we’ve done to date hasn’t shown any difference between variants in a laboratory setting and this is an important point for the [RAT] kits,” Williamson says.

“Having said that, each of the variants may have different kinetics in different people, they may shed differently.

“It’s not as simple as saying that the kits may or may not work, there are so many other factors that come into play.”

That partly explains why viral testing can lack precision: even highly accurate PCR falls short of a 100% strike rate for virus detection.

Paul Griffin, an associate professor in medicine at Queensland University and the director of infectious diseases at Mater Research, says a person experiencing any symptoms should see them as an important marker of illness.

Given that rapid antigen testing can “miss” infection, Griffin says a person with COVID-like symptoms who tests negative on a RAT should follow up either with another test, or a trip to a testing clinic to undergo a PCR.

“People need to understand they [RATs] come with some limitations, as does any test to be honest. They’re not necessarily infallible,” Griffin says.

“We need people to understand that COVID is going to remain a risk in our population, so we do need to look for it.”

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