Keith Jerome thinks he’s onto something.
As director of the University of Washington Virology Lab, Jerome and his colleagues have been working to develop an alternative that would allow patients to be tested for the 2019 novel coronavirus where they’re receiving care—and get results within an hour. Reducing the current time lag of a day or more could greatly speed up treatment of COVID-19 cases as infection and death mount across the country, he explained.
“We’re trying to make this something that’s not a whole lot more complicated than a pregnancy test,” Jerome told The Daily Beast from his office inside America’s first COVID-19 hot zone. Producing more rapid tests will require the lab to build in shortcuts that don’t compromise accuracy, to gain FDA approval, and to partner with manufacturers to produce the test kits.
What amounts to an urgent science experiment, Jerome said, will still take “a couple months, at best,” even if there are no scientific, bureaucratic, or logistical hiccups.
Experts have been saying for some time now that early failures and a lack of urgency from the U.S. government could prove especially costly in helping to flatten the pandemic’s curve as testing capacity is belatedly ramped up. That’s left an eclectic cast of individuals, private companies, and academics to fill a once-in-a-lifetime void.
Jerome is one of them, and he and his team understand that they’re working under tremendous pressure.
“We know how important this is,” he said. “We’re operating in the unknown.”
On New Year’s Eve, Chinese officials notified the World Health Organization that a new type of viral pneumonia was circulating in the city of Wuhan. Less than two weeks later, virologists published the entire genetic sequence of a new type of coronavirus from the same family of viruses that caused the SARS and MERS outbreaks.
That blueprint, or genome, provided an effective means of identifying the infectious agent, now officially called SARS-2-CoV, or the 2019 novel coronavirus. Within two weeks of the release of that critical information, another team, led by researchers in Berlin, published a diagnostic method. The test offered one means by which labs could collect throat or nasal swabs and screen for new cases of COVID-19, as the disease caused by the virus is called, based on isolating and amplifying a genetic signature specific to it.
The race was on as the WHO adopted the German-developed tests and distributed it to dozens of countries. But China, the United States, and several other countries developed their own ways to screen for a modern plague that has since infected over 200,000 people worldwide, including 6,500 people in all 50 states, causing at least 107 U.S. deaths.
As has been widely reported, the early returns on the American side were not good.
President Donald Trump’s federal Coronavirus Task Force has taken steps in recent days to dramatically ramp up capacity. The very recent spike in testing, in turn, has uncovered thousands of previously hidden cases. But as labs scramble to scale up their efforts, interviews with experts and a review of research and testing data suggest that a cascade of errors and a lack of coordination, urgency, infrastructure, and basic lab supplies hampered diagnostic testing at a critical time. Coming back from that won’t be easy.
“I’ve actually been saying that this is going to be a problem since the beginning of January,” said Dr. Krutika Kuppalli, an infectious disease physician in Palo Alto, Calif. and vice chair of the global health committee for the Infectious Diseases Society of America. “You can only scream so loud,” Kuppalli said.
The exponential growth of new cases in the U.S., in fact, suggest that the nation is closely tracking the same COVID-19 trajectory as hard-hit countries like Italy and Iran—and could soon be overwhelmed. But we’re realizing the imminent danger far later than we could have.
A rapid ramp up in testing is critical because understanding COVID-19 tallies and trends in specific locations and among different age groups can inform public health measures like event cancellations, school closures, quarantines and, now, shelter-in-place orders aimed at slowing person-to-person transmission. Testing early and often can turn up milder or even symptom-free cases in younger people who can nevertheless pass on the virus to far more susceptible individuals.
“We need to be thinking along the lines of what South Korea has been doing in terms of their testing and use that as our modeling,” said Jason Kindrachuk, an expert on emerging viruses and testing strategies at the University of Manitoba in Winnipeg whose team established diagnostic testing in Liberia during the 2014 Ebola outbreak. “If we find out who is infected as quick as possible, and if we get people undertaking social distancing, we can actually curb spread and transmission very quickly.”
In a recent Medium post, Belgian researcher Andreas Backhaus explained how intensified and widespread testing in South Korea (with a focus on early test development and drive-through testing locations) turned up an unusual spike in cases among 20 to 29 year olds. The country’s aggressive testing and isolation strategies have slowed its epidemic and contributed to a preliminary country-wide mortality rate of less than 1 percent.
Italy, conversely, has primarily tested patients with apparent COVID-19 symptoms, and older Italians have been hit especially hard, leading to the world’s highest mortality rate at the moment.
“Regarding the U.S., we are still completely in the dark,” Backhaus writes.
By Monday, estimated testing capacity in the U.S. had reached about 37,000 people per day, according to a list maintained by the conservative American Enterprise Institute. Former FDA Commissioner Scott Gottlieb, a resident fellow at the Institute, said in an accompanying tweet that the update on capacity would be the group’s last as more high-volume systems came online.
The tally pointed to how far the U.S. had fallen behind. Although testing capacity has surged since last Wednesday, when President Donald Trump gave a national address about the outbreak, that measure only indicates how many people could be tested. An estimate of total tests performed by Tuesday evening had reached fewer than than 60,000, according to a crowdsourced effort called the COVID Tracking Project. Washington, California, and New York accounted for more than half of that total.
The group effort, which lacks complete data for some states and U.S. territories, was launched in a bid to provide more complete and up-to-date numbers than the Centers for Disease Control and Prevention (CDC), which temporarily stopped posting tallies altogether earlier this month. In a congressional hearing last week, CDC director Robert Redfield said the agency planned to build a data system to aggregate testing data from public and private labs and track the results in real time, but conceded that the agency didn’t yet have such a system in place.
Meanwhile, South Korea had tested nearly 287,000 people by Tuesday.
Some experts have reacted warily to the U.S. testing numbers, noting that a confusing mix of academic, private, state, and federal labs with vastly different turnaround times may be clouding the true tally. “There’s a lot of cooks in the kitchen, which is good in this situation because we need people tested,” Kuppalli said. “Trying to keep track of these numbers can be extremely challenging,” she said, particularly for larger states.
Even so, she and others said getting a better handle on the tallies will be critical for health officials to understand what they’re up against—and whether increasingly strict social distancing measures are having the desired effect. “We don’t know what we’re dealing with until we have those numbers,” Kuppalli said.
Facing intense criticism over the lack of testing capacity at a pivotal moment in the pandemic, the Trump administration on Friday joined private sector officials in promising that more help was on the way. Swiss biotech giant Roche announced that it had received emergency use authorization from the FDA for the first commercial test for the virus, which can be run on its fully automated, high-volume diagnostic systems, provided that hospitals and labs have them. Soon thereafter, Thermo Fisher Scientific followed suit with an announced approval of its own test.
Roche’s highest capacity system can deliver 960 test results per 8-hour shift, or nearly 2,900 results per 24 hours in a continuously running lab. Roche suggested that its two testing systems combined could provide “millions” of new tests a month.
With the arrival of automated tests, a LabCorp release said it expected to be able to perform more than 10,000 tests per day by the end of this week and 20,000 tests per day by the end of the month. Quest Diagnostics announced an identical scale-up in capacity, leading the American Clinical Laboratory Association to estimate a commercial lab capacity of more than 280,000 tests per week by April 1.
At a follow-up press briefing on Sunday, the federal Coronavirus Task Force announced that more drive-thru and walk-thru testing sites would be coming online this week for the hardest hit states, with each site capable of testing 2,000 to 4,000 people a day. In all, nearly 2 million tests would become available by the end of the week, task force officials asserted. “That is really a game-changer for us,” said Admiral Brett Giroir, who is coordinating coronavirus testing efforts for the U.S. Department of Health and Human Services.
“Many of us will believe the testing ability when it happens,” responded Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in comments to The New York Times.
The skepticism follows a series of missteps and overblown promises that have sprung in part from how the U.S. decided to go about testing. South Korea, Canada, and many other countries based their own COVID-19 diagnostics on the WHO-developed test, which identifies the presence of two genes. One encodes a protein embedded in the viral envelope and the second yields a protein that helps the virus produce more RNA. The U.S. CDC instead opted to make its own diagnostic kit, based on a separate protein-encoding gene that helps the virus assemble and make more copies. The test, based on a technique known as polymerase chain reaction or PCR, amplifies the genetic material in nasal and throat swabs collected from patients to see if their mucus contains any signs of the viral gene.
The CDC began sending out its test kits, which consisted of four vials of testing reagents (DNA in a chemical solution) in a small cardboard box, to about 100 testing locations during the first week of February. Theoretically, each kit could provide tests for about 500 patients.
A week later, though, the CDC announced that some states were having problems with one of those reagents. The main problem seemed to be a faulty primer, or a piece of DNA engineered to stick to the viral gene like a bit of Velcro. Primers allow the gene to be copied enough times that it can be identified in the lab, and one of the primers in the CDC test kit, known as N3, repeatedly led to inconclusive test results.
Until the problem could be resolved, the CDC first announced that it would revert to being the sole testing location for the entire country. After further delays, the agency finally scrapped the N3 primer altogether and allowed labs to use the remaining two, but the delay cost them valuable time.
On March 6, President Trump falsely declared that “Anybody that wants a test can get a test.” In fact, a comprehensive review by reporters at The Atlantic (who subsequently helped launch the COVID Tracking Project) suggested that only 1,895 people had been tested by that point, despite high demand. By Monday, after several guests at Trump’s Mar-a-Lago Club in West Palm Beach, Fla., tested positive for COVID-19, a nearby drive-thru site still could test only 65 of the more than 6,000 people requesting it.
Tomer Altman, a bioinformatics consultant in San Francisco, said he has found design issues with all three of the CDC kit’s primers that could potentially reduce the test’s accuracy. Altman has shared his results publicly and been in contact with other researchers who have brought up similar issues. “It further raises concerns that these tests weren’t properly vetted” before their deployment as official testing kits, Altman told The Daily Beast. The CDC shared details of its test Jan. 24, but hasn’t publicly disclosed its internal quality control measures. The agency did not respond to a request for comment by The Daily Beast.
In Canada, Kindrachuk said a test based on the WHO’s recipe has been distributed throughout the country, allowing provincial, territorial, and local labs to conduct their initial screens in pop-up locations. “They’re increasing the accessibility for people, which is fantastic,” he said. “Also, they’re not requiring people to go to clinics or hospitals for testing, which reduces the burden on those facilities.”
Although those tests require confirmation by the National Microbiology Laboratory in Winnipeg, the presumptive positive results can allow for very quick decisions on isolation measures and contact tracing to identify other potential cases. “We need to have coordination to be able to maximize the amount of information we can get out in the shortest amount of time possible to be able to get patients identified, as well as their potential contacts identified,” Kindrachuk added.
Testing criteria also have evolved over time. But the initial CDC requirements were so strict that even the first confirmed case in the U.S., in a man who returned to Washington state from Wuhan, initially didn’t meet them until state officials pushed back, according to The New York Times. Meanwhile, the agency rebuffed offers of help and requests by public and private labs to develop their own tests.
Relaxed CDC and FDA rules under an emergency use authorization have helped break the logjam. But the absence of centralized information on test parameters and availability has spurred news organizations like NBC News to compile lists of how each state health department is handling the patchwork testing process.
Nathan Ledeboer, medical director of the Clinical Microbiology and Molecular Diagnostics Laboratories at Froedtert and the Medical College of Wisconsin in Milwaukee, told The Daily Beast on Sunday that his lab was testing about 50 people per day for COVID-19. The lab is hoping to double or triple its current capacity of about 100 tests per day with existing equipment by the end of the week, and has ordered additional instruments to further expand.
In the absence of sufficient testing capacity, the mad dash by labs to produce their own COVID-19 tests has left them to shoulder most of the burden of sourcing increasingly scarce supplies. “We did a reasonable job of planning ahead for this, and so we have supplies to maintain us for the next couple of weeks or so,” Ledeboer said. But many supplies are now back-ordered, and the lab is trying to hunt down more nasal swabs, genetic primers, and other needs—like a solution that helps preserve the viral RNA prior to testing. “All of them seem to be in short supply,” he said, though he added that federal agencies have been helping to search for alternatives.
His lab and others have reported additional shortages in RNA extraction kits—essential for isolating the genetic material of the virus for the diagnostic test. As a workaround, the CDC relaxed its rules to allow nasal and throat swabs to be combined into a single test instead of two separate ones, effectively doubling testing capacity for many labs.
The shortage of some supplies and tools has grown so acute that the American Society for Microbiology issued a statement last week saying it was “deeply concerned” that clinical labs may be unable to perform COVID-19 tests without them. With expectations of a dramatic scale-up in testing over the coming days and weeks, the professional society urged Congress and the FDA to help provide the funding and authority needed to maintain the supply chain.
Although Ledeboer agreed that the new high-volume COVID-19 tests should significantly improve testing capacity, he said getting them into the hands of labs that were already setting up shop or had been testing, like his, could be crucial to building capacity. His lab uses the Roche system. “If I can use that test, that can allow me to effectively double capacity, if not more, overnight,” he says. “That could be really, really helpful.”
Beyond LabCorp and Quest Diagnostics, the Roche test was being sent to specific labs on a priority basis based on the greatest geographic need, Ledeboer said. His lab wasn’t in the first group to receive them, and he didn’t know when he might have access to them.
In January, the University of Washington’s Jerome and colleagues began working on their own diagnostic test just in case it was needed. It was, despite needing to clear an almost absurd number of hurdles to gain FDA approval, as detailed by GQ.
By last Friday, the lab had assembled a team of more than 70 staff and volunteers from other departments to help crank out its test results, and the number continues to grow. They have set up a drive-thru testing clinic in a parking garage and worked in three shifts to conduct more tests than any other single lab in the U.S.—more than 12,000 in all since they began March 2. About 6.5 percent of recent tests came back positive.
But the virology lab was showing signs of strain as well. Until it can expand its daily capacity with new instruments later this week, the lab announced that it couldn’t take on any new clients. To help meet the crush of demand, the medical school dean issued an extraordinary call last Thursday for qualified graduate students to help staff the lab for a week or more, particularly to help receive and prepare nasal swabs. On Friday, the virology lab sent out a plea to other academic or biotech labs for donations of a specific kind of filter-equipped pipette tip that allows the lab to transfer viral RNA to machines that purify and amplify the genetic material for testing.
“It’s not just about the tests. You can have 1,000 tests, you can have 2,000 tests, you can have a million tests,” Kuppalli said. “You need to have the people who can do the tests, you need to have the supplies to do the tests.”
Labs across the country have likewise raced to produce their own tests with an eye toward faster results. A lab funded by the Bill & Melinda Gates Foundation is working on home testing kits. A hospital lab in Evanston, Ill., is working to produce results in four to six hours. And a Massachusetts Institute of Technology spinoff is seeking approval for a paper-based test that might deliver results in less than 30 minutes.
On Saturday, University of Pittsburgh Medical Center officials announced that they had developed their own in-house test, as well, and would begin testing about 20 people a day at a secure facility by Tuesday. Eventually, they hoped to test hundreds per week.
In an accompanying statement, the university’s medical center officials criticized the federal response as “delayed and limited.” At the Saturday briefing, Alan Wells, the clinical lab’s medical director, said his team had considered developing its test before March 3 and had been in communication with the CDC and FDA, but had been told “that the federal and state authorities would be able to handle everything.”
Just hours after the briefing, Pittsburgh’s Allegheny County reported its first two cases of COVID-19. By Wednesday morning, the tally of positive and presumptive positive cases had jumped to 12.
With reporting by David Axe.
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