Researchers are developing a smorgasbord of tests to detect the
virus that causes COVID-19
In the United States, the average wait time for COVID-19 test
results is about four days. Even worse, 10 percent of individuals don’t receive
lab results for 10 days or more.
Quick reporting of test results helps identify infected individuals
so they and anyone they potentially spread the coronavirus to can be isolated,
preventing further spread of the virus.
“If you have a 14-day lag to knowing if someone is actually sick
and contagious, then they’ll interact with many, many more people in that
period than if you have a one-day or a six-hour or one-hour turnaround,” says
Omar Abudayyeh, a bioengineer at MIT.
Abudayyeh is among the many researchers and companies racing to
develop new and speedier types of diagnostic tests that circumvent clinical
labs altogether. Some of these tests complete their analyses in all-in-one
machines that are portable enough to be set up in schools, nursing homes and
offices. Several companies are developing tests like these that can diagnose
COVID-19 in 30 minutes or less, with a level of accuracy comparable to lab
tests. Others are harnessing the power of the gene editor CRISPR to deliver
rapid results.
And another type of test, made by Abbott Laboratories and granted
emergency use authorization by the U.S. Food and Drug Administration on August
26, works more like a pregnancy test. All it requires is a test card the size
of a credit card, a few drops of a reaction solution and a sample from a nasal
swab. Within 15 minutes, two lines appear on the card if the sample contains
the virus; one line appears if it doesn’t.
The gold standard
The current gold standard for accurate COVID-19 testing is PCR, or
polymerase chain reaction, which can detect even tiny quantities of the virus’s
genetic material, RNA (SN: 3/6/20).
The test requires collecting viral RNA directly from the patient,
typically gathered using a swab inserted deep into the nasal cavity. At a
clinical laboratory, the virus’s RNA is converted to DNA and then run through a
specialized instrument that heats and cools that DNA to multiply copies of it,
making it easier to detect. After repeating the process for around an hour, if
DNA shows up, the sample is considered positive for SARS-CoV-2, the virus that
causes COVID-19.
Such tests are fairly accurate. They miss some people very early
in the infection or because of lab errors, producing false negatives, meaning
that the test results indicate someone isn’t infected when they really are.
False positives — when tests wrongly indicate an uninfected person has the
virus — are rare with this type of technology. So if a PCR test indicates a
person is infected, they probably do carry the virus. The main drawback is the
speed. It typically takes days to get results back, and backups at labs can
drag the process out for a week or two.
Some people find the nasal probe uncomfortable, so other lab tests
have been developed that rely on less invasive samples. On August 15, the FDA
authorized a saliva-based test, SalivaDirect, for emergency use. This isn’t the
first test to detect the SARS-CoV-2 virus in saliva, which is easier to collect
than samples from nasal passages. But its simplified protocol speeds up sample
preparation and bypasses testing supplies that have been in short supply in
recent months. SalivaDirect, however, is not a rapid test. It still requires
processing by clinical laboratories, which contributes to the wait time between
providing a sample and receiving results.
To develop faster tests, companies are taking a variety of
approaches. Funding for some of this work comes from the Rapid Acceleration of
Diagnostics initiative, or RADx, from the National Institutes of Health, which
has invested $248.7 million in seven companies tackling testing challenges.
San Diego–based Mesa Biotech, for instance, received RADx funding
to manufacture a PCR test that replaces an entire clinical lab with a handheld
dock and a single-use cartridge. The company says the proprietary technology in
its Accula test, which has already received FDA emergency use authorization,
can provide a COVID-19 diagnosis in just 30 minutes.
Turning on the LAMP
Other RADx-funded companies, such as Talis Biomedical,
headquartered in Menlo Park, Calif., aren’t using PCR to amplify SARS-CoV-2
viral material. The Talis One system instead uses LAMP, or loop-mediated
isothermal amplification. In a typical LAMP assay, a patient’s nasal or oral
swab sample is mixed with enzymes and specially designed DNA fragments, then
heated to 65° Celsius to copy the viral RNA to DNA and produce many more DNA
copies. With the Talis test, samples are placed in a cassette, popped into a
specialized dock, and analyzed in just 30 minutes.
As opposed to an instrument that cycles between hot and cold, LAMP
heats the reaction to one temperature. “You could run the reaction in a water
bath,” says Nathan Tanner, a molecular biologist at New England Biolabs in
Ipswich, Mass.
In general, LAMP-based diagnostic tests aren’t quite as sensitive
as ones based on PCR, Tanner says, but could be used to test more people, given
their simpler requirements. In one newly described LAMP testing method, a
solution changes color in the presence of 100 or more SARS-CoV-2 RNA molecules.
The authors, who describe the test August 12 in Science Translational Medicine,
propose that the approach, which didn’t detect the lowest viral loads, would be
suitable for identifying individuals with a moderate to high viral load.
Telltale proteins
A third RADx-funded test provides results in a mere 15 minutes.
Rather than detecting viral RNA, the test, by Quidel, based in San Diego,
detects proteins from virus particles. These viral proteins are also antigens,
meaning they stimulate immune responses when they invade our bodies. Such
antigen tests are similar to ones used in doctors’ offices and pharmacies to
diagnose people with influenza.
Don’t confuse antigen tests with an antibody test that detects
antibodies a person develops in response to an infection (SN: 4/28/20) Much
like a pregnancy test, COVID-19 antigen tests use antibodies to detect the
viral proteins and give a yes or no answer, says Kim Hamad-Schifferli, a
bioengineer at the University of Massachusetts Boston.
The Quidel Sofia SARS antigen test has been authorized for
emergency use. Like the other RADx-funded rapid tests, it uses a dock and
single-use cartridges: Instead of making a line on stick the way a pregnancy
test does, the dock detects a fluorescent signal if SARS-CoV-2 proteins are
present.
Abbott Laboratories’ test granted emergency use authorization
August 26 also is an antigen test and, with its card-based technology, is even
simpler. Abbott, based in Abbott Park, Ill., said its test was able to detect
34 of 35 COVID-19-positive patients with symptoms, or 97 percent, in initial
studies.
The benefit: An antigen test doesn’t require any specialized lab
instruments or enzymes. “It’s all self-contained,” Hamad-Schifferli says.
Without a step to amplify viral material, however, an antigen test can be less
sensitive than PCR or LAMP and result in a higher rate of false-negative
results, up to 20 percent per the FDA’s emergency use authorization guidelines
for antigen tests.
That’s because people may produce widely varying amounts of virus,
depending on how long has passed since they became infected. In most people,
the coronavirus is most abundant from a couple of days after infection to about
nine days into the illness (SN: 3/13/20). After that, the immune system kicks
in, preventing viruses from being made. On the other hand, viral RNA can be
detectable in some people for more than a month. A negative result from an antigen test has a
higher chance of being false comfort, so the FDA says that diagnosis may need
to be confirmed with another type of test, like PCR.
A new kind of rapid test
Even though antigen tests typically are not as accurate as
standard PCR or the new rapid tests, they could play a crucial role helping to
end the pandemic — if their use becomes widespread. As of now, though, even
Abbott’s 15-minute test still needs to be ordered by a doctor and performed in
a health care setting, so that can provide hurdles to its use. But what if
people didn’t even have to leave home to get a test?
That’s what Hamad-Schifferli and her colleagues are working on.
The idea is to build a cheaper test that doesn’t involve a dedicated instrument
— just a paper strip and a signal detectable by eye. Such a simple test could
be used more widely by people at home. “It would be a game changer,” she says.
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