Taking the Fight to the Virus, Step 1: Rapid Turn-Around Screening Tests
"Testing, testing, TESTING!" insisted my friend at Bronx Superior Court, "We can't have juries in here until we can test them all." That's the criminal justice bottleneck: no one can be indicted because there is no grand jury empaneled. Then there's the question of how to open schools. With wait times of a week or more for RT-PCR test results, contact tracing isn't the public health measure it could be, and the virus goes on spreading. Without systematic testing, “We might as well put duct tape over our eyes, cotton in our ears, and hide under the bed,” Dr. Margaret Bourdeaux, research director for the Harvard Medical School Program in Global Public Policy told Vanity Fair Magazine.
SARS-CoV-2 is a hit & run adversary; if we're slow to identify infected individuals, we miss our shot. By the time the symptoms set in to where a person is taken to the hospital, the virus has done its damage and is on to the next person. If we’re to seek and destroy, we can't keep our eyes wide shut. "This is not a war, but in a certain way, it is, against the enemy which is called the virus. And that virus is very sneaky and stealthy." said NIH director Dr. Francis Collins on Meet the Press. By the time people experience symptoms, including fever, the virus has already reached its peak population and is on the decline. It's the damage it has left behind that sets other events in motion.
The only way to know when to isolate/quarantine and the only chance antiviral medications have to engage the virus is to identify infected individuals early. The way to do that is with frequent, rapid-result testing. A more "sensitive" test, represented by pink bars on the graph of virus spread below, helps, but the more important factor is test frequency.
Enter personal, portable testing, of two types:
Cue Health’s solution looks like something from the Sharper Image Catalog
Most approved point-of-care tests remain a 'clinical grade' option. Models from Cepheid, Cue Health, Mesa Biotech, Talis Biomedical, Becton Dickinson and Quidel have received Emergency Use Authorization from the FDA. Some of these are miniatures of the RT-PCR type, while others are antigen tests that can be run faster and at lower cost.
Screening tests are a 'surveillance grade' option. Most of these are antigen tests. They're less sensitive, but they're cheaper and faster than the RT-PCR type and are far better than infrared thermometers for early COVID detection. Some resemble home pregnancy tests.
“My next point is about surveillance testing,” HHS Assistant Secretary for Health Admiral Brett Giroir testified before congress July 31. “We should separate the clinical diagnostic system from the public health surveillance system. Diagnostics are for those who are hospitalized, symptomatic, or with high risk exposures. Surveillance testing can be for college students, or potentially students in K-12, or workers in environments that are not high risk, or other similar situations. This type of surveillance can occur in non-CLIA labs like university research labs, or veterinary diagnostic labs, outside of the FDA authorization system at low cost and very high throughput. We are working closely with states and universities to implement this type of system, and many of them, like LSU, already have. We have all the tools, the supplies, and the regulatory framework to enable a robust surveillance system throughout the nation.”
The Trump Administration appears to have found religion with respect to the point-of-care tests, and is making them available to nursing homes. Even as their take-charge point man on testing testified to Congress, the RADx program announced funding for seven new test technologies, three of them point-of-care instruments. There remains real question, though, whether the administration will back the kind of large scale roll-out of antigen tests that would make them a more effective alternative to touchless thermometers for regular screening.
----- <> -----
On May 8 the first emergency use authorization was granted for an antigen test for SARS-CoV-2, the virus that causes COVID-19, to the Quidel Corporation of San Diego. At about that time a self-contained test unit debuted called the Abbott ID NOW, and many small labs and institutions placed orders.
Then an NYU study published sensitivity values for the Abbott ID Now that clearly were lower than achievable with conventional RT-PCR tests, giving antigen tests a bad name (though in fact the ID Now uses a third technology, isothermal nucleic acid amplification).
----- <> -----
“I am blown away.”
“That was awesome.”
"I feel some hope, finally!”
Dr. Michael Mina, a young Harvard School of Public Health researcher with a bright smile, had won over the host and panel of This Week in Virology with the power of a straightforward set of ideas: test people frequently, use a cheap test, don’t keep people waiting for the result, worry less about the test’s sensitivity. "Don't let the perfect be the enemy of the good," commented Dr. Anthony Fauci when asked about Mina's remarks on the show the following day.
A problem with antigen test approval is the FDA requirement that a test be 80% as sensitive as PCR. The way that 80% is defined, though, is not directly relevant to how antigen test proponents aim to utilize them: to identify those individuals who are currently contagious, the yellow-green zone of the graph below. Additional discussion can be found in this Medcram video featuring Dr. Roger Seheult and Dr. Mina.
From: https://www.medrxiv.org/content/10.1101/2020.06.22.20136309v2.full.pdf [shaded areas added by author]
Do surveillance grade tests require FDA approval? Currently yes, but perhaps Giroir, who was interim head of FDA before assuming his current position, is suggesting that a different category of certification implies a different sensitivity standard, or it could be that Giroir has something else in mind when he speaks of surveillance. Public health officials, analysts & researchers often deploy an array of tools to gain insight into what’s happening within a population, including wastewater analysis or the “pooling” of cultures. If there are differences in approach between the young Harvard researcher Mina and the Trump Administration’s point man Giroir, it’s likely we’ll see them play out. Louisiana State University was specifically cited by Giroir, while the Broad Institute, with which Mina is affiliated, is working with Harvard and Colby College to develop protocols for reopening.
Mina has suggested personal tests could be simplified to the point of being litmus strips on paper, and if the government can print money in large quantities when it needs to, why not paper litmus strips? The U.S. has always been behind where we need to be on testing, so while we have plenty of experts interested in taking the fight to the virus, the virus has typically moved on to another host by the time we firmly identify an individual as having COVID-19. Something clearly needs to be done, on a grand scale. “That's the kind of thing that I personally, along with many others in other parts of the government, are working on night and day to try to do a better job of this. You're right. We have to come up with a better turnaround time,” continued Dr. Francis Collins, NIH Director, on Meet the Press.
“So if you’re going to be looking at schools, if you’re going to be opening things up, testing is how you know” says Dr. Daniel Griffin of Long Island’s ProHEALTH. In discussions with a New York media company, “They basically were saying ‘we want to open,’ and I said, if you really want this to work, you’re going to test everyone every morning before they go to work. If you want to do this, it’s going to cost a certain amount of money. Maybe right now that’ll be $30 a day, but pretty soon it’ll be $10, and before we know it, we know we can get that down to a dollar or two. A dollar or two a day, to open up the economy, per person? That’s not even a cup of coffee at Starbucks.”
Dr. Michael Mina is co-author of:
NEW! The authors of the paper above now have a website: www.rapidtests.org
Dr. Mina was a guest on: