Posted on 04/09/2020 9:16:27 PM PDT by SeekAndFind
Providers and public health officials hope that more COVID-19 testing will help contain spread of the disease. But efforts to get tests done faster and results quicker are hindered by how many tests can be quickly deployed and how accurate they prove to be.
Three decentralized tests for SARS-CoV-2, the virus that causes COVID-19, have been granted Emergency Use Authorization from the U.S. Food and Drug Administration in the past 10 days.
Decentralized molecular tests are meant to bring lab-quality test results while the patient is with the provider so that they can guide treatment decisions. These tests, and any accompanying equipment, need to be small or portable, require minimum sample processing, and little training to use correctly in low-complexity testing environments. The newly authorized tests from Cepheid, Mesa Biotech, and Abbott Laboratories use instruments that have already been for other indications, such as influenza testing.
New York Gov. Andrew Cuomo this week said the COVID-19 epidemic might be resolved with "an inexpensive home test or point-of-care test that can be brought to volume," while former FDA Commissioner Scott Gottlieb declared the authorization of the Abbott ID Now test to be a "game changer" on Twitter.
Experts in clinical virology, however, are somewhat more cautious.
Richard Hodinka, a professor of microbiology at the University of South Carolina School of Medicine in Greenville and former director of the clinical virology laboratory and the Children's Hospital of Philadelphia, is an authority in molecular testing at the point of care.
"Having these systems available for SARS CoV-2 testing may be extremely impactful and offer a number of distinct advantages," Hodinka said in an email. However, "companies need time to ramp up their manufacturing capacity and product inventory in order to supply material to any and all customers desiring to use their products," he said.
Frederick Nolte, director of clinical laboratories at the Medical University of South Carolina in Charleston, said his lab went live a week ago with the Abbott high-throughput system and is now testing 400 patients a day, adding staff, and hoping to max out at about 1,000 tests a day, but the lab has not yet been able to get any decentralized testing up and running.
Alex Greninger, assistant director of the University of Washington clinical virology laboratory, said, "every new test is helpful" since they can build capacity and relieve the existing strain on the supply chain of other testing. "What's interesting about these [decentralized] platforms is that there's no particular logistics for the sample, so you don't have to drive or fly them to a reference lab," he said.
Manufacturing and distribution
To make a dent in the ongoing COVID-19 outbreak, the tests—and the test instruments—need to be distributed in high enough numbers. Among the three decentralized tests, Abbott has the biggest installed footprint and highest current manufacturing capacity.
Specifically, Abbott has approximately 18,000 instruments in the U.S. and will ramp up to make 50,000 tests per day, according to Norman Moore, director of scientific affairs for infectious diseases at Abbott Diagnostics. The firm expects to ultimately produce more than a million tests each month.
In contrast, Cepheid has 5,000 systems in the U.S., and a representative said that the firm is ramping up test production. Mesa Biotech has previously said it has a few hundred users, mostly in physician office labs, and the firm can make 10,000 tests per week. It is also "actively adding personnel, additional shifts, and fast tracking an already planned facility expansion" according to Laura Dullanty, the firm's senior manager for marketing and commercial services.
But, many of the rapid testing instruments typically run one, or a few tests at a time, so users need multiple instruments to increase throughput. "It is not a solution for high-volume testing, it is a niche solution for those situations where you need results quickly," Nolte said.
On one test, a strong positive COVID-19 result—which presumably is due to a patient having a high viral load—can be detected in five minutes. But a negative result requires 13 minutes, translating to fewer than five negative tests per instrument in one hour.
"Most patients in most locations will be negative," Nolte noted.
The Cepheid and Mesa tests take significantly longer to run each test—45 minutes and 30 minutes, respectively, with the potential of an increase in throughput using a different instrument.
A Cepheid representative also noted that the firm's COVID-19 assay has been granted federal approval to run on other instruments. Testing on these instruments was designated for labs authorized to perform high and moderate complexity tests, but the representative noted that some hospitals use the high-throughput systems nearer to patients, essentially in decentralized lab spaces.
Nolte said his hospital system in South Carolina has a large telehealth presence, and it started a drive through sample collection tent early on in the outbreak.
"There are four stations patients can drive up to, and I was thinking, what if we had" a way for patients waiting in their cars to get results, he asked. "But that is difficult to scale up, because you need lots of instruments."
The three new tests can reach different points distal to the lab. The Cepheid system is often dubbed "nearpatient" because it is more of a bench-top instrument. The Abbott system is the next smallest, and also sits on a surface, while the Mesa system is handheld, so could theoretically be used at the bedside.
But although point-of-care tests are being touted as helping small clinics and rural areas that don't have access to testing, Nolte emphasized that low-throughput testing could become a bottleneck in itself.
"Once volume scales up, it is no longer a workable solution."
The tests are also currently being distributed selectively to areas hardest hit by the outbreak.
"We're working with the [Trump] administration to deploy the tests to areas where they can have the greatest impact," said Moore at Abbott.
Nolte's lab is running the Abbott m2000 test on two instruments they already had, plus one that the company supplied them with to facilitate COVID-19 testing. "We've used that system for years, it's a workhorse … They guaranteed us a supply of reagents and we were the second lab in the country to go live with it," he said.
Nationally, the positivity rate for COVID-19 testing is approximately 8%, Nolte said, while in New York City is nearing an average of 30% with some neighborhoods as high as 70%. Nolte's lab in South Carolina currently has a 6% positivity rate.
"We're not in the hot zone yet," he said.
From a high-level viewpoint, he pointed out that even if manufacturers can make enough tests, the sample collection materials, and competent staff, also need to be in place and at scale.
Test accuracy
To prevent positive cases from slipping through the cracks and continuing the chain of transmission, tests need to be accurate, which is a function of sensitivity, specificity, ease of use, and potential for contamination.
"When I tell people we launched our assay, the first question is, 'What is the sensitivity and specificity,' and I say, 'I can't tell you,'" Nolte said. The test is analytically very sensitive, and based on the primer and probe selection, it should be specific for this coronavirus, but that is as much as is currently known.
The same holds true for the EUA decentralized tests, which have all been validated in the lab with contrived samples.
All three tests are explicitly authorized to be run by trained operators in patient care settings outside of the clinical laboratory environment, and all three accept raw samples.
According to the instructions for use of each test, the reported limit of detections differ slightly among these tests: Cepheid detects as few as 250 copies per milliliter, Mesa's limit is 200 copies per reaction, and the Abbott limit of detection is 125 genome equivalents per milliliter.
However, whether the limit of detection and contrived sample analysis will translate into actual sensitivity in real patient samples remains to be seen.
"Everyone wants to know the clinical sensitivity and specificity of all of the tests, but I do not think you will see this information until the dust starts to settle," said University of South Carolina School of Medicine's Hodinka.
Abbott's Moore also highlighted that "performance characteristics, including accuracy data, will continue to be collected in the field."
Nolte noted that even though the outbreak is challenging, there still needs to be stringency among lab professionals, and he is drafting a white paper with his colleagues at the Association of Molecular Pathology noting that the validation for emergency use that the FDA is now accepting is "the absolute minimum anybody would consider before launching a clinical assay."
This may be why all three decentralized tests also explicitly state, "Negative results do not preclude SARSCoV-2 infection and should not be used as the sole basis for treatment or other patient management decisions."
Using high-sensitivity molecular tests outside of the controlled lab environment has historically been an issue, as laboratorians have worried that non-expert use might lead to contamination and false results. In a number of cases previously reported—such as at Geisinger Health, Henry Ford Health System in Michigan, and in some pediatric hospitals —decentralized MDx systems have been adopted but are run by designated trained users, housed in special containment boxes, or only used in the laboratory for stat testing.
In an ideal world, the point of care molecular tests would have been evaluated using clinical samples run by actual end users in the field to make sure the accuracy is the same as in the lab.
Unfortunately, a thorough trial of these technologies "is just not possible in the throes of the outbreak," Hodinka said. This is especially true "given all of the patient testing that laboratories are currently doing, and particularly because of the shortage of collection swabs, transport medium, test kits, instruments, reagents, [and] consumables," he said.
"Everyone is playing catch up right now and doing the best they can under very extenuating circumstances," Hodinka said.
This story first appeared in our sister publication, 360Dx, which provides in-depth coverage of in vitro diagnostics and the clinical lab market.
Well I trust it more than Costello’s
The FDA needs to get out of the way and let the private sector get to work on this problem.
We’re pretty much past the point where flattening the curve is going to help, especially since in many areas of the country it won’t happen until next month.
This is a way for individual people to open up their personal economy.
Abbott knows who is on first.
WHO?
It’d be nice to be able to get a sense of false results, but most likely they will need to be in widespread use for a couple of months to nail that down.
:)
No, WHO was thrown out of the game by the umpire.
Why?
;)
True curve is already flattened. hopefully the test can let us get people back to work and stop the insanity
We were supposed to have virtually unlimited drive up testing early on at multiple locations nationwide and citywide and a list of pharmacies that could do it in every community.
Promises made but not delivered.
Hydra chloroquine was supposed to be a publicly available virtually prophylactic treatment that could be used to treat people almost before they got it that is the covin infection.
No it wasn’t promised in blood but it was a commitment made and it’s not being delivered.
Trump as a good man but the bureaucrats in the medical industries are blocking him at every turn plus the trump haters and the TDS party worldwide. This is why people are not as confident as they could be.
Our medical professionals have grossly lied to us regarding scale and scope.they resist and refuse to deliver that which was indicated.
Trump delivered the hospital beds. trump delivered the ventilators. trump has actually acquired the medications but the democrat doctors association of America with their ability to pronounce death curses over people’s lives have dug their heels in and they’re not getting their ass in gear that makes america sick.
The reason they don’t want to cut loose and make contesting happen full throttle is because they want to stay ahead of the crisis and protect their little fiefdoms. The CDC and the FDA have utterly failed to provide for the health and safety of the American people by resisting what is absolutely known factually to work and save lives to try and protect their own reputations and expand Hillary Clinton type of socialized medicine.
” Hydra chloroquine was supposed to be a publicly available “
I really don’t think it’s ‘hydra’ lol
I’ve had about enough of these experts.
That’s my voice to text program not my typing.
Why is out with an injury. Someone threw a bat in his direction and he ate it. ;^P
WHAT?!?
WHAT is on third trying to steal home but the catcher has it quarantined. :)
How about testing 100 people at a time and then by person if the group is positive.
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