Pivoting quickly from the sidelines to front-and-centre of our national COVID management strategy, rapid antigen tests (RATs) are now in such high demand that there have been calls for market regulation to stamp out price gouging and stockpiling. State governments have ordered more than 84 million kits for the coming weeks to help meet demand.
Given the lightning speed of their introduction as a basic healthcare necessity, it’s understandable that many of us have been left with unanswered questions about RATs. How do they work, and why are they only now being rolled out?
Rise of the RAT
The days of striving for COVID zero are now firmly behind, and Australia has taken its first steps towards living with COVID as an endemic virus.
With the emergence of the exceptionally virulent but potentially less lethal Omicron strain, our leaders are keen to capitalise on the opportunity to begin easing restrictions. With a national double-vaccination rate over 90%, we have an opportunity to step carefully towards a more normal existence, and a future in which COVID simply simmers away in the background like its seasonal flu cousins.
As we proceed through this transition phase, keeping tabs on the virus’s spread remains key to retaining our grip on public health and safety. But the stringent testing and tracing approach adopted in the pandemic’s early days simply can’t be sustained as case numbers grow.
“Living with the virus means adjusting our lives to respond to the threat that COVID-19 poses, and rapid antigen tests will assist greatly in allowing us to protect the vulnerable in the community, keep workplaces safe, and hold large mass gatherings in a safer way as we move to endemicity,” says Hassan Vally, Associate Professor in Epidemiology at Deakin University.
Performed at home and requiring no specialist training for either testing or results analysis, RATS help to spread the burden of monitoring the virus across the whole population. With results ready to read within 30 minutes, RATs will help us to assess our individual risk as restrictions drop away.
How do RATs work?
Throughout the pandemic, PCR tests have been integral to our monitoring of COVID’s spread. Characterised by an uncomfortable brain-tickling nasal swab, PCR tests have been, and remain, the gold standard in viral detection, with an accuracy rate above 90%. They work by amplifying parts of the virus’s genetic code, using an enzyme called Taq polymerase to duplicate viral DNA strands many millions of times over.
This signal amplification makes them exceptionally sensitive. They are capable of picking up even very low viral loads from the earliest stages of infection through to the late post-infectious stage. However, the process takes many hours and requires sophisticated lab equipment and specialist technicians.
RATs, on the other hand, have no capacity for signal amplification. They work by detecting a protein on the surface of the virus directly from the sample being analysed – usually a nasal swab. The sample is mixed with a solution that breaks the virus apart to reveal these proteins, and the resulting mixture is applied to a paper that contains an antibody that leaves a telltale coloured strip, akin to a pregnancy test, if the proteins are present. Most tests return a result within half an hour.
As their sensitivity is directly tied to the viral load present in the sample, RATs are generally only useful in detecting high levels of the virus. In practical terms, this means that they will only give accurate results within approximately the first five days of infection, and only if sufficient levels of the virus are present.
It’s early days for antigen testing in Australia, and local data on the accuracy of RATs remains poor, but data is amassing in countries that adopted antigen testing much earlier in their pandemic response, such as the UK. A study from Oxford University indicated that RATs were able to detect approximately 80% of infections with high viral loads when compared to PCR tests.
Thus we have now two distinct categories of test: the free-to-access but costly to provide PCR test, which is exquisitely sensitive but slow to deliver results; and rapid antigen tests, which are costly for consumers but comparatively cheap for governments, less sensitive than PCRs but able to produce a result in the time it takes to savour your morning coffee.
Should we be concerned about inaccurate results?
At first glance, the discrepancy between the sensitivity of these two test types seems concerning. Can we feel confident in the results of at-home testing if they’re missing up to 20% of infectious cases that would have been picked up by PCR tests?
First, we need to understand the different risk levels posed by false positives and false negatives. False positives are undoubtedly a nuisance as they can delay an indvidual’s return to normal activity, including work. But from a public health perspective, false positives are of little concern. Anyone returning a positive RAT will require a PCR confirmation test, which will weed out any false positive results.
False negatives, on the other hand, pose a genuine risk to community health. Positive cases who believe that they’re virus-free will accordingly fail to isolate.
“The implications are that there are many infectious people who could be unknowingly spreading the disease,” says Professor Adrian Esterman, Chair of Biostatistics and Epidemiology at the University of South Australia.
Luckily, the stand-alone figures on RAT accuracy don’t convey the whole picture.
This is because it is important to distinguish between detecting positive cases and picking up on those who pose a credible transmission risk. While RATs may miss up to 20% of positive cases, this is most likely to happen in asymptomatic people with a low viral load. When viral load is sufficient to make a carrier highly infectious, it is also likely to produce a positive RAT.
“This is actually an important property of these tests in that rather than detecting virus in the body at any level, they are able to detect when virus is being shed in sufficient amounts to make a person infectious, which makes them a really good screening tool,” says Vally.
Esterman agrees, noting that the transmission risk from asymptomatic carriers is no longer a pressing concern, now that COVID is circulating widely in the community.
“Transmission rates of asymptomatic people range from 0–2.2% compared to 0.8–15.4% for those who are symptomatic,” he says. “The risk is of transmission is much lower if asymptomatic.”
Does it matter which RAT you take?
The TGA has now approved 18 different antigen tests for supply and home use in Australia, and that number is set to increase over coming months. Are there any differences between available tests? Should we be prioritising some tests over others for more vulnerable populations and settings?
Esterman explains that the TGA have separate sensitivity categories for approved tests, ranging from ‘acceptable’ at >80% through to ‘high’ sensitivity at >95% – the equivalent of a PCR test.
“For high-risk settings like aged care, clearly RATs with very high sensitivity would be preferable,” he says.
For the general public, however, any test you can get your hands on will do the job.
“With all classifications having a sensitivity >80%, they are all perfectly good as a general screening tool.”
What challenges lie ahead for RATs?
Although their speed and ease of use makes RATs a valuable addition to the COVID-management toolkit, the road ahead is not without speedbumps.
Easy and equitable access will be vital. Given the narrow window of optimal testing time while viral load is high, RATs will only fulfill their potential if they can be used for regular surveillance testing by all sectors of the population.
“Their accuracy is much improved when they are used serially, that is when tests are repeated over multiple days,” says Vally.
In a recent study from the National Institutes of Health, researchers found that rapid antigen tests had a sensitivity (>98%) comparable to PCR for identifying infected individuals if used at least every three days. Such a usage pattern would require large numbers of tests to be reliably available to the public for many months to come. Despite the current difficulties in sourcing tests, Vally does not believe the shortages will persist in the long term.
“We are going through a challenging time right now due to the change in testing requirements,” he says.
“The demand for rapid antigen tests is far exceeding supply. This situation should be relatively short-lived as governments procure additional supplies and these arrive.”
Supply issues should further ease as the TGA expands the number of authorised tests, but equitable distribution to vulnerable or disadvantaged people remains a challenge not yet adequately addressed.
“In terms of who pays for these tests, this is a really important policy issue that needs to be resolved,” says Vally.
“I am of the view that rapid antigen tests, now that they have been catapulted to play such a vital role in our response to the pandemic, at the very least need to be subsidised heavily for all of the community and should be free for those on low incomes. Price should not be a barrier for using these tests, for anyone.
“I worry that some politicians are out of touch with just how much of a financial burden these tests are for some people, and I hope that common sense leads to the right outcome at the national cabinet meeting this week.”
Esterman agrees. “The federal government should see this as an investment and provide them free to the public,” he says.
“Instead, they see it as a chance for pharmacies and supermarkets to make a bigger profit. The government is considering supplying them free to those on concession cards, but this is as usual too little too late.”
A further issue is our lack of RAT reporting. If you return a positive RAT at home, you’re then required to take a PCR test for confirmation, and it’s only these PCR results that are recorded by the health system to track the spread of the virus. But with testing facilities already stretched beyond capacity, the feasibility of logging all positive cases this way is already an issue.
Instead, it’s time to consider adopting RAT reporting methods like those used in the UK, which enable positive RATs to be reported from home using a simple QR code scan. This would allow us to continue to track the spread of the virus as case numbers skyrocket, a vital step in allowing health services to predict and prepare for surges in hospitalisations.
“Case numbers are still incredibly important because even if Omicron is milder, the sheer volume of cases will eventually swamp our health services,” says Esterman.
“I think endemicity is still a long way off, but RATs definitely have a strong role in bringing outbreaks under control.”