Testing backlogs, reagent shortages, and limited access have contributed to inadequate testing for COVID-19 in the US and elsewhere. But in recent months, new types of assay that promise to offer quicker, cheaper, and more user-friendly features have begun to roll out. Saliva tests, for one, are gaining traction as screening tools for universities and professional basketball teams. Antigen testing is another approach that, if given regulators’ blessings, might give consumers the ability to take their own tests at home and get results on the spot.
Several diagnostics firms are currently working to gain regulatory approval and bring products like this to market in huge numbers.
“This is like a wartime effort, there are many fronts that we’re trying to fight this disease,” says Stephen Tang, president and CEO of OraSure, which is working on a test that members of the public could take themselves. The firm plans to manufacture millions of antigen tests annually.
Results from such tests can be available in less than an hour and the fact that people could take them themselves has convinced some that antigen tests could be a game-changer in fighting the pandemic.
There is also potential for high-throughput antigen tests to be used in lab settings as well, to speed up mass testing across whole countries or regions.
In essence, antigen tests are the reverse of antibody tests. In the latter, viral proteins, the antigens, are distributed across a plate within the test device. If an individual’s blood sample contains antibodies against SARS-CoV-2, those antibodies will bind to the antigens, triggering an emission of light or color change, indicating a positive result.
Antigen tests, in contrast, contain antibodies on the plate instead. These are just like those generated naturally by people and animals to fight off a COVID-19 infection. When a sample, usually a nasal swab, containing virus particles is applied to the assay, the antibodies bind to the viral antigens and similarly trigger a visible result to show that someone is presently infected.
Compared to PCR and antibody tests, antigen tests take a bit longer to develop because manufacturers have to be sure that they have identified the ideal antibodies that bind to SARS-CoV-2 and not to proteins from other viruses or microbes. Then the production of those antibodies using animal models is scaled up.
At least two firms, Quidel and BD, have already obtained Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for antigen tests designed to be administered by healthcare workers.
Quidel reports that the sensitivity of its test—the extent to which true positives are detected—is 96.7 percent. In BD’s case, the reported sensitivity is 84 percent. Both firms claim their tests have a specificity of 100 percent, meaning the tests should produce no false positives. But earlier this month, Ohio Governor Mike DeWine tested positive on a Quidel antigen test only for three subsequent PCR tests to show he was in fact negative for SARS-CoV-2 infection.
“We take the issue regarding Governor DeWine very seriously and we are investigating the matter through our Quality Management System, trying to learn the specifics of the issue in order to get to the root cause. At this time, there is nothing to suggest that there is a problem with the Sofia® 2 instrument or the Sofia SARS Antigen FIA rapid test,” a spokeswoman for Quidel wrote in an email to The Scientist.
The World Health Organization (WHO) does not currently recommend antigen tests for clinical diagnosis because there is not enough data to support their accuracy. In fact, based on the accuracy of rapid diagnostic tests for other respiratory infections such as influenza, the WHO says the sensitivity of antigen tests for COVID-19 could lie between 34 percent and 80 percent, far below the performance of traditional PCR-based diagnostics for SARS-CoV-2 infection.
This has not stopped India, to name one country, using antigen tests en masse. Health providers there have used antigen tests for months now to screen many thousands of people. And in July, authorities approved a new rapid antigen test developed by Indian firm MyLab Discovery Solutions. It is already on sale and costs roughly $6 per test.
Only a few North American companies developing at-home rapid antigen tests have released validation results so far but Sona Nanotech is one of them. CEO Darren Rowles says that in evaluations using about 30 different viruses, bacteria, and fungi, the antibodies selected by Sona Nanotech only formed a successful bond with SARS-CoV-2 and SARS-CoV, the original SARS virus that emerged in 2002.
Antigen test developers can decide to target a particular type of protein on the virus. “In our instance, it’s specific to the spike proteins on the surface,” says Rowles. Quidel’s and BD’s antigen tests, in contrast, target the nucleocapsid (N) protein.
In lab experiments using 30 swab samples from healthy individuals, the Sona Nanotech test correctly identified 29 of the samples as negative. The SARS-CoV-2 virus was then artificially added to these 29 samples and the test subsequently identified 28 as positive. The company has not yet reported the results of studies in the field using a mix of positive and negative samples from participants. Once they are published, Rowles says, the firm hopes to apply for EUA from Health Canada and the FDA.
“The idea is for healthcare workers to be taking it first and then some modifications to the test platform to allow at-home use,” he explains.
OraSure’s at-home test will require the user to perform a quick nasal swab and then apply a solution to the swab, which itself will function very much like a pregnancy test, says Tang.
“You can read the test in under an hour,” he explains. “It reads as a control line and a test line so if there are two lines present, you are coronavirus positive and should seek to self-isolate yourself.”
OraSure has not published any validation data for its tests yet but the firm has committed to manufacturing them in large volumes if EUA is granted. The company recently announced that it would be hiring an additional 177 staff to help increase capacity.
“We’re going to devote a considerable amount of that capacity to COVID-19,” says Tang.
There are real benefits to increasing the availability of tests for COVID-19, says biomedical scientist David Grenache, the chief scientific officer at TriCore Reference Laboratories.
“By deploying more antigen tests that can be done rapidly, we will increase the likelihood that we’ll detect infected individuals,” says Grenache, who is not involved in the development of antigen tests himself.
However, there are stumbling blocks to consider. “There’s always concern about patients doing their own tests because they’re not trained in laboratory techniques,” says Grenache. Inadequate swabbing could mean an inaccurate result.
And then there are politics. Because mask-wearing has become a politicized issue in the United States, he notes, the uptake of at-home antigen tests might not be spread evenly across all parts of society.
Antigen tests may also struggle to correctly identify people as positive if they have lower levels of the virus in their system, such as during the latter stages of an infection when the worst of the illness is over.
That’s not necessarily a deal-breaker, says Eleanor Riley, an immunologist at the University of Edinburgh in the UK. “Very low levels of virus aren’t a problem because you’re probably not infectious,” she says.
Riley points out that rapid antigen tests for malaria are widely used. These are often self-administered by travelers, for example. “The precedent is there and those cost a dollar a pop or less,” she adds.
We’re still months away at the very least from having millions of at-home rapid antigen tests available for people to use. In order for that to happen, governments would likely have to plough billions of dollars into the manufacturing of such tests. But the other place that antigen tests could make a difference is in professional labs, which are currently processing huge numbers of PCR tests every day around the world.
Lab-based analysis of antigen tests is more sensitive than the rapid tests used at home or at the point of care, Grenache says, because the light-detecting machines in a lab used to identify the reaction associated with antibody-antigen binding are much more accurate than the systems built in to self-testing kits. And, in principle, lab-based antigen tests could be quicker to do than the PCR assays we’ve relied on so far.
“Those tests will be much easier to scale up,” says Grenache. “Once those are available, assuming the performance is good, that’s the type of test we would offer in my lab.”