Special Report: How federal snafus slowed testing at a top U.S. hospital

  • Tue,7 Apr 2020 06:42:30 PM

By Peter Eisler and Chad Terhune

CHARLOTTESVILLE, Virginia (Reuters) - The lab directors at the University of Virginia Medical Center felt powerless.

In early March, people began arriving with symptoms of COVID-19. One complained of a cough and had just returned from Wuhan, the Chinese city where the outbreak erupted. An elderly patient, already on end-of-life care, had a mysterious respiratory infection. Another, struggling to breathe, had come from a nursing home.

Each needed a test for the coronavirus. The hospital had none to offer.

"Testing is so critical," said Amy Mathers, an infectious disease physician at the hospital and associate director of its clinical laboratory. "Everybody was just hounding me, and I could see how not having in-house testing was getting worse and worse and worse for the patients and the staff."

Federal authorities had promised for weeks to provide tests for public health labs. They also pledged to quickly approve additional diagnostic tests developed by hospitals and private companies.

UVA's medical center, part of a top-flight medical school, had banked on those assurances in developing a strategy and backup plans to ensure it could test patients for the novel coronavirus that causes COVID-19. But its efforts were stymied at almost every turn by federal health agencies, the rapid collapse of medical supply chains, and the slow pace of test development by commercial labs and companies. Hospitals in Seattle, Sacramento, Pittsburgh and elsewhere ran into some of the same obstacles.

Even so, within about two weeks of seeing its first coronavirus patients, the Virginia hospital was able to build a robust, in-house testing operation. The medical center now is analyzing scores of samples a day for itself and more than a dozen other hospitals across the state that still lack enough tests to offer the sick. Its capacity exceeds some state labs around the country that relied solely on tests supplied by the federal government.

The path there, however, cost the hospital and caregivers precious time and resources. It left patients in limbo and endangered doctors and nurses, who were unable to diagnose the disease or properly allocate scarce protective gear, let alone assess and contain the threat.

While patients continued to arrive at the medical center with COVID-19 symptoms, hospital staff at UVA spent days scrambling to meet federal requirements for conducting tests in-house. They scoured university labs to satisfy obscure equipment requirements, and they begged colleagues at other institutions for specimens of the virus that were in frustratingly short supply.

The hospital's travails in developing its own testing capabilities demonstrate the challenges for health systems frustrated by the U.S. government's inability to provide emergency supplies and equipment to battle the coronavirus. Its struggles also offer an inside look at a regulatory system that slowed America's early response.

"It felt like it took three months to get through those two weeks," said Melinda Poulter, a clinical microbiologist and director of the UVA hospital lab. "It felt like a constant uphill battle with people throwing rocks at you from the top of the hill."

The two federal agencies that oversaw testing, the Centers for Disease Control and Prevention and the Food and Drug Administration, have cast blame on the other for delays in testing.

CDC spokesman Benjamin Haynes acknowledged that "this process has not gone as smoothly as we would have liked."

FDA Commissioner Stephen Hahn defended his agency's work at ensuring tests produced accurate results. "The FDA's regulations have not hindered or been a roadblock to the rollout of tests during this pandemic," Hahn said in a statement.

Public health specialists and doctors say the United States lost valuable time as CDC and FDA officials clung to standard procedures for too long while hospitals such as UVA's stood ready to help limit the spread of the virus.

"We could have saved probably tens of thousands of lives by doing testing early and really isolating and quarantining all known cases," said Lawrence Gostin, a professor and director of the O'Neill Institute for National and Global Health Law at Georgetown University. "But that window of opportunity is gone."

More than 370,000 coronavirus cases have been confirmed in the United States as of Tuesday, including 11,000 virus-related deaths.

 

THE "RECIPE"

As cases of COVID-19 emerged in the United States in late January, the UVA lab team wasn't immediately concerned about having tests ready.

Genetic tests for the coronavirus had been developed quickly in China, and the World Health Organization had made a similar testing protocol available to any country that wanted it. In the United States, the CDC opted to develop its own protocol, as it typically does when new viruses emerge. It would serve as a template that labs around the country could use to set up their own testing operations.

Poulter and Mathers were confident they could make the CDC protocol work in their lab, which routinely develops genetic tests to diagnose patients for flu and other viruses. Besides, commercial test manufacturers were assuring hospitals that they would have tests available that could promptly process large numbers of samples.

By mid-February, Poulter and Mathers had settled on a plan: develop a test using the CDC protocol and have it ready "early on, while our patient volumes are still low," Poulter said. Later, when caseloads climbed, "we expected the commercial vendors would have higher throughput options available."

That plan unraveled on both fronts.

The CDC's test was issued first to public labs at the state and local level in early February. Problems surfaced within days. The CDC test was unreliable, and the agency began to work on a fix.

As they awaited more details from the CDC, Poulter and Mathers considered starting from scratch on their own test "“ a process well within the UVA lab's capabilities. But that would have required getting FDA approval, a notoriously slow, complex process they had little experience navigating.

Typically, hospital labs have broad leeway under federal law to develop in-house diagnostic tests. But because the Trump administration had declared the virus a national emergency, tougher regulatory rules were in effect.

The emergency declaration gave drugmakers more flexibility to develop vaccines and antiviral treatments for COVID-19. But it also put new restrictions on diagnostic tests developed by individual labs. Those tests now required FDA approval for even slight deviations from the CDC protocol.

Poulter decided to bank on the CDC's test.

"I said, "˜You know what? This is going to be a whole lot faster,'" Poulter recalled. "And I was wrong about that."

The CDC didn't have its updated test kit to public health labs until February 28, and revised instructions for any lab using the government test were posted on the FDA website several days later.

The CDC protocol involves a number of steps: First, a mucus sample is taken from a patient, usually by nasal swab. The next step involves chemically extracting genetic material, known as RNA, and converting it to its DNA equivalent. Then, the DNA is run through a process called polymerase chain reaction, or PCR, in which analytic equipment determines whether the sample contains the genetic fingerprint of the virus.

The CDC protocol was specific in the types of chemicals and equipment that labs were required to use. Almost immediately, hospitals were pitted against one another as they sought the needed supplies.

"It's like the CDC had a recipe and you had to use the exact brand of olive oil, the exact brand of pasta," Mathers said. "And because there was only one pathway for every lab to do this, everyone was trying to get those brands, so the shelves were bare. And then you had to cook it all on a very specific stove, and those stoves are back ordered by six to eight weeks."

 

BACKUP PLAN

As Mathers shopped for supplies, the pressure to expand testing continued to grow.

Early U.S. coronavirus cases mostly involved people who had traveled to China or other places where the virus was prevalent. But on Feb. 26, the CDC announced that a California woman had contracted the virus despite having no recent travel history or contact with anyone known to be infected.

It was an inflection point: the first reported U.S. case of "community transmission," a term used to describe the spread of the virus when the source is unknown. And there was no telling where the virus was moving elsewhere.

Absent a test they could run themselves, most hospitals had limited options: send samples to the CDC in Atlanta or to a state lab and wait days for results. With limited capacity, the CDC and its state counterparts set stringent criteria. Patients experiencing symptoms such as fever or difficulty breathing could only be tested if they were linked to another confirmed case or had traveled to China or other hot spots.

By early March, the pressure to develop an in-house test "was becoming more urgent," Mathers said. Patients with COVID-like symptoms were starting to show up at the hospital, and few met the strict rules for government testing.

As Poulter and Mathers struggled to find the supplies to adopt the CDC testing protocol, they turned to their backup plan: purchasing ready-to-use tests from medical companies.

But when Poulter checked with vendors, the response was invariably the same: They still were waiting for their own tests to get FDA approval. "All they could tell you was, it was under review," she said. "It became clear it wasn't going to happen in time, that we were going to have to do something on our own first."

Under increasing pressure to expand testing, FDA officials had removed some bureaucratic obstacles. They were working with numerous firms developing tests for sale as well as large commercial labs looking to test hospital samples shipped to their facilities. But it took until mid-March for a company to win agency approval. Hahn, the FDA commissioner, had expressed concern about sacrificing reliability for speed, noting that wildly inaccurate results would be worse than having no tests at all.

"It's important to remember that false negatives or positives can be detrimental to making sure we are treating patients early, without delay, and also not quarantining healthy individuals," Hahn said on March 7.

 

FRANTIC SEARCH

Poulter and Mathers continued to contact one supplier after another for the chemicals and equipment needed to set up the CDC testing protocol, and each offered the same answer: out of stock.

Mathers called the university's finance department to get an inventory of all lab equipment on campus. Then she began walking from lab to lab. She found two with the type of PCR analyzer required for the CDC test. But there was a catch. They were slightly different models geared more toward research than clinical use. The hospital would have to verify that those machines delivered accurate results and submit that information to the FDA.

"That took at least a day," Poulter said. "And that was just one little piece of what we had to do."

As soon as that hurdle was cleared, "I just went back to the labs with a cart and took them," Mathers said. The researchers using them for academic work were crushed. "I felt so badly for them, but it was our only option."

While Poulter continued to search for the chemicals needed to run the CDC test, she and Mathers finally got some promising news.

Laboratory Corporation of America Holdings, a chain of commercial labs, had a test ready to go "“ and the company promised that samples sent in by the hospital would be tested within 72 hours. The UVA lab signed up immediately.

On March 10, the medical center sent LabCorp its first samples, prioritizing elderly patients and those with pre-existing conditions "“ the groups at greatest risk of dying. Two days later, the hospital got its first results.

"Then," Poulter said, "it all fell apart."

 

"BEHIND THE EIGHT BALL"

After quickly acting on that first batch of samples, LabCorp began taking more time to turn around results, Poulter said. It went from two days to four days, then five days and six, and ultimately as many as 11 days from when samples were submitted.

Mike Geller, a spokesman for LabCorp, said "we are aware that some test results are taking longer than the expected timeframe and we are working around the clock to complete those tests." He said results are available in four to five days in most cases.

As frustration mounted at the UVA hospital, the back-ordered chemicals needed to run the CDC test finally arrived at the lab. With their scavenged PCR analyzers, Poulter and Mathers were ready to begin validating their in-house testing operation. But they faced one more obstacle: They needed a genetic sample of the coronavirus as a control to confirm the accuracy of their new test, and none was available.

Mathers began reaching out to labs nationwide for help. She struck gold with a cold call to a researcher at the University of Washington in Seattle. The area was a hotspot for the coronavirus; the researcher was willing to send samples.

On March 18, the UVA hospital lab finally began its own testing.

In just the first day, Mathers said, the lab had completed upwards of 20 tests, and had more results than it had received in days of waiting for government labs and LabCorp to test. "We've been testing nonstop ever since, but it never should have taken so long," she said. "The additional regulation in the throes of an emergency outbreak really hamstrung the labs."

Roger Klein, a physician and former adviser to the federal government on clinical laboratory issues, said the FDA should have turned sooner to academic medical centers with plenty of testing experience. "These aren't fly-by-night people selling a test on the street corner," he said.

Hahn, the FDA commissioner, said his agency has provided "unprecedented flexibility" to labs and test manufacturers during this pandemic.

"The FDA has been extremely proactive and supportive of test development by all comers "“ laboratories, and large and small commercial manufacturers "“ offering our expertise and support to speed development and to quickly authorize tests that the science supports," Hahn said in a statement.

Last week at the White House, Hahn joined President Donald Trump and other administration officials to celebrate a milestone: more than 1 million samples tested nationwide.

Hahn also unveiled a new on-site test from Abbott Laboratories that can deliver results within 15 minutes at a hospital or doctor's office. Trump unboxed the toaster-sized machine in the Rose Garden.

"That's something that's a game changer," Trump said of the Abbott test. "Our testing is also better than any country in the world."

Many hospitals and state officials disagree. The level of virus testing remains low in many states, and doctors and patients are left waiting days for results. The governors of Ohio and Illinois both complained in recent days about substantial delays in getting results from private labs.

On Monday, the U.S. Health and Human Services Inspector General's Office published a survey of 323 hospitals and found severe shortages of testing supplies and delays in getting results remained a significant problem.

"When patient stays were extended while awaiting test results, this strained bed availability, personal protective equipment supplies and staffing," according to the inspector general's report.

And shortages of key components "“ from chemicals to swabs "“ continue to slow the expansion of testing across the country. Hospitals and private labs have been forced to hunt for scarce supplies without much help from the federal government, said Krutika Kuppalli, a physician with expertise in infectious diseases and pandemic preparedness.

"We have been behind the eight ball every step of the way during this pandemic. Our government wasn't thinking ahead," she said.

By late March, the UVA lab had built more than enough testing capacity to meet its needs, using not only the CDC protocol but also a high-volume commercial test that became available after the lab got its own test up and running. So it began offering to test samples sent by other hospitals in the region.

The hospital said it was still one of a few in the state with its own testing capacity. By Monday morning, it had run more than 1,500 tests, nearly 30% of them for other hospitals that lack the materials or capability to do their own testing.

"We want to offer this to everybody," Mathers said. "We're all in this together. There's never been a better example of that."

 

(Reporting by Peter Eisler in Washington and Chad Terhune in Los Angeles. Additional reporting by Justin Ide in Charlottesville, Virginia. Edited by Blake Morrison.)

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