- The CDC reported a flaw in its coronavirus test kits to the FDA on February 10, but it took another 16 days for the agency to notify state labs of the solution.
- The faulty component, which caused most state labs to receive inconclusive results, was never essential to the test’s function.
- The FDA eventually decided that state labs could simply throw away the chemical causing the problem. But the labs weren’t permitted to use their original tests until February 26.
- For the latest coronavirus case total and death toll, see Business Insider’s live updates here.
- Visit Business Insider’s homepage for more stories.
Wisconsin’s State Laboratory of Hygiene had been waiting to get coronavirus test kits from the Centers for Disease Control and Prevention for two weeks before its first shipment finally arrived.
The kits came late in the evening on Friday, February 7, even though the CDC had publicly released the details of its test on January 24. The Food and Drug Administration approved the kits for emergency use 11 days later, on February 4 — two weeks after the US’ first COVID-19 case was reported in Washington state.
But when technicians at the state lab in Madison tried to verify that the CDC tests actually worked after they returned to work on Monday, the results were inconclusive. Without working test kits, the laboratory couldn’t begin processing specimens from potential coronavirus patients.
Another 16 days would pass before the CDC provided a solution, during which time the state lab couldn’t perform any tests. The fix, when it eventually arrived, was shockingly simple: The laboratory could use the original test after throwing away one of its ingredients, which had never been essential to the test’s function in the first place.
“In a public health emergency, it’s kind of ironic that all the states had a test that worked. They just didn’t have a protocol that worked,” Alex Greninger, assistant director of the University of Washington Medicine Clinical Virology Laboratory, told Business Insider. “What changed was they just said, don’t use that reagent.”
Delays in testing have likely allowed the coronavirus to spread throughout the country, since limited testing makes it harder for health officials to find, isolate, and trace infected patients. More than 200 people in the US have died from COVID-19 and nearly 14,000 have been infected, compared to just dozens of cases reported in February. All the while, a perfectly good tool for testing more patients was sitting in state laboratories, awaiting authorization.
It took more than a month after the CDC developed its test for state labs to start testing
The coronavirus test developed by the CDC is a polymerase chain reaction (PCR) test — it compares the genome of the coronavirus to samples taken from a throat swab or saliva sample. The same type of test is commonly used to diagnose tuberculosis, influenza, and measles.
PCR tests look for specific genetic sequences in a virus using short sections of nucleotides called primers. These primers are essentially chemicals, or reagents, that bind to the genetic sequence a lab wants to target. Some PCR tests have two or three reagents, while others have only one.
“If you have a lot of them, it takes more time to do a test, but you have higher accuracy,” a spokesperson for the Wisconsin lab told Business Insider.
By the time the FDA approved the coronavirus test, the CDC was investigating around 260 patients, using samples that had been sent to its headquarters in Atlanta. Eleven people had already tested positive across five states. On February 6 and 7, the CDC shipped 90 test kits to state public health labs.
But one of the CDC’s reagents turned out to be faulty, causing the majority of the state labs to come up with inconclusive test results. The Washington State Public Health Lab was among those who received shipments containing the defective reagent. The state reported the first COVID-19 case in the US and is now one of the states with the most severe outbreaks.
Only a handful of state laboratories were able to certify their CDC tests using all three reagents — the Illinois Departments of Public Health, for instance, told Business Insider that there were no issues with the kits they received in early February.
But the Wisconsin lab got inconclusive results. The lab said it informed the CDC of the issue on February 10 — the same day the CDC told the FDA about the problem. Two days later, the CDC publicly admitted that there was an issue with the test kits.
The agency considered sending a new batch of reagents to state labs, which would only delay testing by a few days, the New Yorker recently reported. But 11 days later, labs were still in the dark as to whether the problem had been fixed.
“We are working with FDA, who is the one that has oversight over us,” Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Diseases, said during a press call on February 21. “We still consider it a priority to get the kits out to patients as soon as possible. It is overridden by the priority to make sure that the test is correct.”
Finally, on February 26, the CDC and FDA gave all 50 state labs permission to use the original tests without the third reagent.
The majority of state labs began testing for coronavirus in late February and early March, using the kits they had received on February 7. New York’s state lab was never able to verify the original CDC test, the New Yorker reported, but for most others, a test with two reagents had been enough to diagnose COVID-19 all along.
“You don’t need three [reagents]” Greninger said. “Three is kind of overkill.”
Neither the FDA nor the CDC responded to Business Insider’s inquiry about why the agencies took this long to re-authorize the original test.
‘It was not something you could flip a switch on’
Even after getting the green light to use the original tests, state labs still faced several hurdles in getting potential patients tested. First, they had to perform a new quality check using just the two reagents instead of three.
“A very small number of state/city labs — five in the US — were asked to perform a verification on their second set since it didn’t contain the N3 primer,” a spokesperson for the Washington State Department of Health told Business Insider.
For many labs, including the one in Washington state, that meant another 48 hours before they could begin testing. For others, like those in Wisconsin and Pennsylvania, it would take even longer — until March 2.
“It was not something you could flip a switch on,” a spokesperson for the Pennsylvania Department of Health told Business Insider.
Some state labs, like those in Washington and Wisconsin, received additional CDC tests without the third reagent from February 26 onward.
But then another issue arose. At the time state labs began testing around February 28, the CDC only allowed tests for people with symptoms so severe that they required hospitalization, people who had recently traveled to countries with high case totals (like China or Iran), or people who had been in contact with someone confirmed to have the coronavirus.
A spokesperson for the Wisconsin lab said it had the capacity to test people starting February 28, but no cases in the state met the CDC’s criteria until March 2. By that point, 90 cases had been confirmed nationwide, though that’s probably an underestimate. (According to researchers at the Seattle Flu Study, there were probably already around 570 coronavirus cases in in the greater Seattle area by March 1, mostly connected to the first COVID-19 patient.)
‘By the time they send things out, it ought to be foolproof’
Greninger said one reason to include a third reagent in the coronavirus test was to prepare for the possibility that the virus might mutate. An additional primer could offer a safety net to detect the virus if its genetic sequence changed.
“They were sort of trying to make an assay that could detect other SARS-like coronaviruses that circulate in bats,” Greninger said. “For whatever reason, it just didn’t work. That happens all the time when you make PCR tests — some of the primers just don’t play ball together and you just gotta toss ’em.”
But health experts told Business Insider that distributing a test with a faulty reagent was somewhat unusual.
“By the time they send things out, it ought to be foolproof,” William Schaffner, a CDC adviser and professor of infectious diseases at Vanderbilt University, told Business Insider. “As a friend of mine said, it ought to be a gorilla test. Even a gorilla can run it.”
“I don’t know where the glitch came from with that reagent,” he added. “Something went wrong, that’s for sure.”
On a February 21 press call, Messonier said that problems with the test kits were “a normal part, unfortunately, of these processes.”
More than a manufacturing issue
When the FDA first approved the test kits on February 4, the agency did so under an “Emergency Use Authorization” (EUA), which expedites the process of diagnostic testing during a public-health crisis.
The first EUA was issued 11 days after the CDC announced its test. From there, it took the FDA an additional 22 days to award another EUA for that very same test without the one nonessential ingredient.
“The EUA is like a recipe that you have to follow,” Greninger said. “It’d be like if I sent you a recipe for a pound cake and I put 10 times more salt in it than I should. And you’re like, this pound cake sucks, but you have to follow the recipe because it’s the approved recipe. And then I wait 16 days and I change the recipe. You still have the same ingredients, but you’re just using them the right way now.”
At a press briefing on March 7, FDA commissioner Stephen Hahn suggested it was manufacturing problems that made it difficult for public-health laboratories to start using the CDC test. The FDA and CDC, he added, had quickly resolved the issue by using a third-party manufacturer.
“Quality testing, distribution of tests, and verification of the tests in labs can take a few days, although FDA, CDC staff, and the laboratory community are working around the clock to speed up these processes,” Hahn said.
But Greninger said the lag time between identifying the faulty reagent and issuing another EUA was “the frustrating part of the story.”
“We would be telling each other a different story if it were a manufacturing issue,” he said. “The honest truth is, whatever it was, they just got rid of the reagent.”
Greninger’s lab at the University of Washington began using its own COVID-19 test on March 2 — just two days after the FDA started allowing certified academic hospital labs to perform their own tests.
His lab is now administering between 1,800 and 2,000 tests per day and diagnosing more than 100 to 150 patients each day in the Seattle area, he said. He said he’s still getting kits with the faulty reagent included.
“We take that tube and we throw it in the trash so we don’t accidentally use it,” Greninger said. “It’s still there.”