This company has a better version of a simpler, faster Covid-19 test

August 6, 2020 steven

In some parts of the U.S. right now, it can take weeks to get results for a simple Covid-19 test, a delay that renders the results largely useless.

So a handful of city governments and schools are turning to an entirely different type of Covid-19 test that they say is simpler, easier, and most importantly faster — and therefore more meaningful.

The tests are like a streamlined version of the far more common PCR tests used to diagnose Covid-19. The test’s simpler process requires fewer materials and less equipment; the results can be read by eye within an hour. But the technique — known as LAMP — can also, in some situations, be less sensitive and less accurate than PCR tests. And it can be hard to run many of the tests at once outside of a central laboratory; people can only work so quickly.

Enter Color Genomics, a California-based, direct-to-consumer DNA test company that says it has solved many of the problems associated with the technique. Its Covid-19 tests are just as accurate as PCR tests, according to the documents it filed to the Food and Drug Administration for an emergency authorization. And it’s automated the process enough to run thousands of tests each day. Already, Color is processing about half of all the daily tests run in San Francisco and returning results in one to three days.

But Color’s improvements come with tradeoffs. Experts told STAT that an additional step in the company’s process means it costs more and takes more time than others. Color’s automation setup might not be cheap to replicate around the country. And since Color uses the same swabs and some of the same chemicals that so many PCR tests rely on, it could also face some of the same supply chain issues that have plagued other testing efforts.

“It opens up the flexibility of the supply chain to this PCR alternative, which is nice. But it doesn’t overcome some of the common barriers to testing,” said Matthew Lalli, a researcher studying genomics technologies at Washington University in St. Louis.

The technology behind the tests is known as LAMP, or loop-mediated isothermal amplification. It’s been around since the 1990s, when a Japanese scientist developed it as a less-intensive alternative to PCR, or polymerase chain reaction-based tests.

Both PCR-based and LAMP-based tests look for genetic strands of a given virus in a sample collected from a patient. But PCR requires that a sample be repeatedly heated up and cooled down in precise intervals using an expensive machine known as a thermocycler.

LAMP does not require a thermocycler. The reaction can be run at a constant temperature — about 65 or 70 degrees Celsius, or 150 degrees Fahrenheit. That makes it far simpler to run, and far less equipment-intensive. The reaction also creates a change in the acidity level of a sample; often, a compound that changes color from pink to yellow in different pH conditions is added to the tube, which means anyone can read the results.

Before this year, LAMP-based tests have been used for screening animal food for Salmonella as well as diagnosing C. difficile infections in humans and chlamydia in koalas.

And several groups around the world are developing new Covid-19 testing programs around LAMP. Many are relatively basic: In Racine, Wis., for example, researchers are running LAMP tests in an unused corner of city hall with minimal equipment and supplies, as Wired reported last month. Another Wisconsin group is running tests in elementary school parking lots. And a hospital in Germany is experimenting with a LAMP-based surveillance protocol developed at the Broad Institute.

But many of those point-of-care LAMP tests have an admitted shortcoming: Though they are simple, cheap, and fast, they are also less sensitive than PCR tests. Because of that, it’s often used for screening groups to try to catch most of the people who might have a disease — not to formally diagnose someone.

There’s a type of PCR, for example, that “has a nearly perfect sensitivity. You cannot beat that,” said Jonathan Schmid-Burgk, a professor at University Hospital Bonn who has also developed a test that relies on LAMP technology and who is not affiliated with Color Genomics.

Color Genomics’ LAMP-based tests solve that problem by adding a little complexity. Before Color actually runs the LAMP protocol on a swab, it extracts and purifies the RNA. This step, which is done on a particular machine that uses magnetic beads, concentrates the RNA.

“This [step] directly translates to sensitivity,” said Schmid-Burgk — that is, it can make it more likely that a test will give accurate negative results.

The company’s EUA paperwork indicates that for more than 500 samples, its test gave the same results as the Covid-19 diagnostic test developed by the Centers for Disease Control and Prevention.

Color’s been using the technology for Covid-19 tests since April; the company got the first-ever FDA emergency authorization for the test in May.

The 7-year-old company is far better known for selling genetic tests — work that investors and governments alike have been willing to fund. It raised $215 million from venture capitalists and received grants worth millions through the NIH’s All of Us program, which intended to sequence q million Americans’ genomes.

When the pandemic came to the U.S., Color expected that it would be helping labs figure out how to automate certain processes to take some of the human effort out of running Covid-19 tests.

“The deciding factor for us was the realization that no one we were talking to was taking an integrated approach similar to what had made us successful in genetics,” said Color spokesperson Benjamin Kobren. “Lab people were trying to build a lab. Logistics people were trying to set up drive-through sites, and so on.”

But in the early days of the pandemic, supplies to run PCR tests were in very short supply. Color’s team worried that competing with other labs for limited supplies might exacerbate the testing problem. So they looked at alternate protocols, like LAMP, that wouldn’t add stress to some of the PCR supply chains.

“The thing that made it good for point-of-care testing was actually the thing that we thought would make it really good for super high-throughput labs — which is that it’s a relatively simple process,” said Color’s CEO, Othman Laraki. “We’re able to run almost the entire process on a single robot.”

San Francisco’s city government began working with Color in early April, according to a spokesperson. Color is one of a handful of labs behind the CityTestSF program, which offers testing by appointment for San Francisco residents and essential workers. The company charges about $100 per test, a San Francisco city representative told STAT; that figure is about the same as Medicare’s current reimbursement rate for Covid-19 PCR tests.

Kobren, the company’s spokesman, noted that the price of a test can vary, depending on how many tests are included in a particular contract and what kind of group that contract covers.

Since the program began, Color says it has been able to deliver results far more quickly than many other laboratories. Results from Color are usually available within one to three days, the company’s website states.

That kind of turnaround time has been critical, said Sarah Owens, the deputy press director for San Francisco’s mayor.

“Effective contact tracing depends on Covid-19 results being received in a timely manner,” Owens said. Getting results back quickly “allows us to contact people who test positive and begin the process of reaching out to their close contacts more quickly, thereby slowing the spread of COVID-19 in the community.”

Color’s LAMP tests are also the foundation of the University of Southern California’s testing program; the company said in a press release that it expects to run at least 500 tests per day on samples collected at three different sites.

Experts caution Color’s test isn’t suddenly going to replace PCR tests around the country.

For one, its product is proprietary; only Color’s lab can process the tests, necessarily limiting how many can be run in a day. Color’s worked hard to increase the number — its automated process can now handle 10,000 tests per day.

That RNA purification step that Color added comes with a price.

“Purifying RNA is really tedious,” said Schmid-Burgk. Adding purification may increase a test’s sensitivity. However, it also increases the time a test needs to process and can ultimately cuts down on the number of tests a lab can process each day.

“You kind of lose the speed advantage by adding an RNA extraction step,” said Lalli, the Washington University in St. Louis researcher.

Color’s automated setup is also expensive. Replicating Color’s automation would require about $500,000 worth of equipment, according to Chris Mason, a computational genomics specialist at Weill Cornell Medicine.

Even existing clinical laboratories with deep pockets might hesitate before ordering equipment and supplies to set up an entirely new protocol when PCR machines are already sitting in their facilities.

“Most labs have PCR equipment, but many do not have LAMP, so it logistically makes it more difficult to bring up in the scale needed for widespread testing,” a Quest spokesperson noted.

Another potential challenge: While some parts of Color’s LAMP reaction uses machines and chemicals that are completely distinct from those needed for PCR tests, Color’s process still requires some of the same supplies — like swabs, RNA extraction kits and pipette tips.

The New York Times reported that those supplies may become scarce again soon — which means that even Color itself could ultimately be unable to use its lab’s full capacity or unable to process tests as quickly as it is now.

But Color’s team is optimistic that it’s prepared for that possibility. The company is hiring more people, adding additional equipment, and partnering with other labs that can run PCR tests in order to handle potential increases in demand. And Kobren, the company spokesman, told STAT that the company believes its automation “enables us to reduce per-test consumption of scarce resources such as pipette tips and tubes.”

“We continue to invest resources and R&D to make our processes as efficient as possible.”

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