NEW YORK – A partnership between an established infectious disease diagnostics team and a high-throughput laboratory with a pedigree in sports drug testing has led to a 10,000 per day increase in COVID-19 testing capacity in the Los Angeles area. The partners, Curative and KorvaLabs, set up a designated COVID-19 lab in less than one month and have received Emergency Use Authorization from the US Food and Drug Administration for a lab-developed test.
Called the Curative-Korva SARS-Cov-2 Assay, the test garnered EUA last week. According to the EUA summary, it detects SARS-CoV-2 nucleic acids in oropharyngeal, nasopharyngeal, and nasal swabs, as well as oral fluid specimens. The latter is notable, as it could circumvent swab supply shortages and sets the stage for the possibility of at-home self-collection.
Jeffrey Klausner, acting medical director at the lab and a public health expert at the University of California, Los Angeles, explained in an interview that the oral fluid sample is a combination of upper respiratory tract fluid and saliva.
To collect the sample, a patient is instructed to cough three to five times and retain the product of the cough in their mouth, then swab the inside of the mouth, including under and on top of the tongue, the roof and sides of the mouth, and the upper and lower gums, for at least 20 seconds, Klausner explained.
The method doesn't require any special collection device, and almost any type of sterile swab can be used, he said. The sample is authorized to be self-collected in the presence of a healthcare professional, which reduces the risk to providers and increases scalability.
The FDA has said of late that some saliva-based tests it initially reviewed were not reliable enough, but it recently authorized a LDT saliva test from Rutgers University. Last week the agency said it does not know what combination of factors led to the test having good sensitivity, but noted it may perhaps be related to nucleic acid stabilization in the transport media.
The Rutgers test saliva sample is collected into a device from Spectrum Solutions that stabilizes RNA. Similarly, the Curative-Korva test uses a stabilizing media, DNA/RNA Shield from Zymo Research.
For the Curative-Korva test, specimens are transported and stored at room temperature and tested within 24 hours of collection.
Because the lab was set up for COVID-19 testing, the team could also make decisions about workflows that might avoid other bottlenecks as well. For extraction, it uses a kit from Norgen Biotek, for example, that it can perform either manually or in an automated protocol with a Tecan robot.
The reverse-transcription step of the test uses the Applied Biosystems TaqPath 1-Step Multiplex Master Mix, and the qPCR step uses the US Centers for Disease Control and Prevention primers and probes provided by Danaher's Integrated DNA Technologies. It is authorized to be processed on the BioRad CFX 96 Touch, BioRad CFX Connect, or the Roche LightCycler 480 II real-time PCR systems.
The test has a reported limit of detection of 200 copies per milliliter in oral fluid. It was also subjected to a small study using clinical samples.
Specifically, to evaluate supervised self-collection, the team contacted 52 subjects who had already tested SARS-CoV-2 positive at a Los Angeles drive-through. A clinician drove to their homes, and observed self-collected oral fluid and nasal samples, and also collected a nasopharyngeal sample.
Using its test, the lab found 100 percent positive and negative agreement between oral fluid swabs and nasopharyngeal swabs, and 97 percent positive agreement and 100 percent negative agreement between nasal swabs and nasopharyngeal swabs.
A COVID-19 lab
Curative was founded in Menlo Park, California by Fred Turner, the former CEO of Shield Bio. Klausner had a previous relationship with Shield Bio, having consulted for that firm's multidrug-resistant gonorrhea panel. Shield had also been developing molecular diagnostics for sepsis.
Shield Bio had the distinction of being the first US service lab to use Oxford Nanopore sequencing in its workflow. The company shuttered in December, however, which Tuner said this was due to an investor pulling out unexpectedly, "which left the company unable to raise further funding to continue."
Curative was then founded by Turner to focus on sepsis, but it pivoted to respond to the COVID-19 epidemic, Klausner said.
Klausner said Turner reached out about a month ago to see if they could find a lab that already had the necessary equipment in the area and that could quickly be adapted for COVID-19 testing. "We looked around Southern California, identified KorvaLabs, and they were interested in partnering," Klausner said.
KorvaLabs is a high-complexity CLIA lab based in San Dimas, California that performs clinical, sports antidoping, research, and specialty testing.
Klausner became the unpaid volunteer medical director for KorvaLabs, he said, since they needed someone with infectious disease training.
In an email, Turner noted that it took Curative about 10 days to develop the SARS-CoV-2 assay. Then the team brought it to KorvaLabs, validated it, and ran the first test about five days later.
As a new private lab now focused only on COVID-19 testing, the lab was able to be flexible in finding reagents and systems to develop the most efficient workflow, Klausner said, particularly with respect to extraction kits and swabs.
"We're not experiencing any current bottlenecks, and we're doing up to 5,000 tests a day," he said.
Klausner noted that the City and County of Los Angeles drive-through test sites are using the Curative-KorvaLab test service, and the lab is also testing first responders.
"There is a continued high and steady demand," he said. The lab is not yet testing at capacity, and is looking at other ways to test, as well.
"Because the FDA authorized supervised self-collected specimens, we are looking into whether that could be supervised at home through telehealth," Klausner said. This would decrease exposure for healthcare workers, and require less resources than the somewhat complicated and resource-intensive drive-through test sites, he said.
Turner confirmed that the lab is now providing testing for both the city and county of Los Angeles, as well as the city of Long Beach, The LA County Fire Department and Sheriff's Department, and also the state of Alaska, the state of Florida, and the US Air Force.
"A lot of these connections have been inbound requests from people looking for testing, and then one customer connecting us with others they know that are looking for testing capacity," Turner said.
As a public health expert, Klausner said he has been concerned by erosion of the US public health infrastructure in recent years, in both the public health practice side and the laboratory side. He has worked in public health on development and evaluation of infectious disease diagnostics for more than 20 years, including tests for HIV, STIs, and tuberculosis, as well as more recently working on tests to detect gonorrhea superbugs.
For the current pandemic, "It is distressing and saddening to see how this has played out," Klausner said. "Every chance I get I try to advocate for more public health resources and investment into public health professional training, anticipating a crisis like this, and we now see what the consequences of our lack of investment are," he said.
Nevertheless, Klausner points to the fact that the Curative-KorvaLabs partnership was able to set up a brand-new testing lab, going from zero tests to an EUA test running 5,000 tests per day, in four weeks.
"It is pretty amazing. I wish we could replicate what we did around the country," he said.
Furthermore, Klausner noted that the cost to get a lab started was not that high in the big scheme of things, and the lab can very quickly be self-sustainable with contracts and relationships with payors.
"There are obviously a huge amount of funds made available to invest in the COVID-19 response — it is somewhat perplexing to me why we haven't seen more laboratories like this come up across the country," Klausner said.