Pooled testing not going as planned
As nation needs more coronavirus tests to mitigate the spread, the once efficient approach isn’t working.
Earlier this summer, Trump administration officials hailed a new strategy for catching coronavirus infections: pooled testing.
The decades-old approach combines samples from multiple people to save time and precious testing supplies.
Federal health officials like Dr. Anthony Fauci and Adm. Brett Giroir said pooling would allow for constant surveillance of large sectors of the community and said they hoped it would be up and running nationwide by the time students returned to school.
But now, when the nation desperately needs more coronavirus tests to get a handle on the virus’s spread, this efficient approach has become worthless in many places, in part because there are simply too many cases to catch.
Pooled testing only works when the vast majority of batches test negative. If the proportion of positives is too high, more pools come up positive — requiring each individual sample to then be retested, wasting chemicals.
Nebraska’s state public health laboratory was a pooling trailblazer when it began combining five samples a test in mid-March, cutting the number of necessary tests by about half.
But the lab was forced to halt its streak April 27, when local positivity rates — the proportion of tests that turn up positive — surged past 10%. With that many positives, there was little benefit in pooling.
“It’s definitely frustrating,” said Dr. Baha Abdalhamid, assistant director of the laboratory. In combination with physical distancing and mask-wearing, pooling could have helped keep the virus in check, he added. But the window, for now, has slammed shut.
“A lot of us are still in the evaluation stage, trying to figure out what problems this will solve,” said Rachael Liesman, director of clinical microbiology at University of Kansas Medical Center, which processes several thousand coronavirus tests a week but has yet to bring pooling online. “But it could create new problems, too.”
Despite relatively widespread acceptance in countries like Israel, Germany, South Korea and China, pooling’s rise to prominence in the United States has been sluggish.
It wasn’t until July 18 that Quest Diagnostics became the first commercial lab to receive emergency authorization for pooled testing from the Food and Drug Administration. Since then, Quest has deployed its approach — which batches four samples at a time — in three of its labs, in California, Massachusetts and Virginia, with plans to roll out more on an undisclosed timeline, according to a company representative.
Another large testing company, LabCorp, was given the go-ahead on pooling July 25 but has yet to debut the procedure in any of its facilities.
Certain hospital systems have also received emergency approval from the FDA to run pooled tests. UC San Diego Health can run pools of five samples on a machine made by pharmaceutical company Roche and will likely receive clearance for two more in the coming weeks, according to Dr. David Pride, director of the health system’s molecular microbiology lab.
The strategy has already made significant headway in some parts of the country. In New York, where test positivity rates have held at or below 1% since June, universities, hospitals, private companies and public health labs are using the technique in a variety of settings, often to catch people who aren’t feeling sick, said Gareth Rhodes, an aide to Gov. Andrew Cuomo and a member of his virus response team. Last week, the State University of New York was cleared to start combining up to 25 samples at once.
At Poplar Healthcare, a lab services company based in Memphis, Tennessee, a team led by chief executive James Sweeney is pooling several thousand samples each week. By batching up to seven samples, Poplar is funneling crucial intelligence to schools, fire departments and more, Sweeney said. In a lot of these groups, coronavirus positivity rates are below 1% he added.
Pooling accounts for about one-third of the samples processed at Poplar, Sweeney said, adding “that percentage is going to get much higher.”
But in many other regions, experts are having trouble clearing the hurdles to benefit from pooling — in part because needs differ so vastly from institution to institution and even from test to test.
“There’s been a lot of concerns about all the challenges,” said Dr. Bobbi Pritt, director of the clinical parasitology laboratory at Mayo Clinic, which processes tens of thousands of coronavirus tests each week but has yet to roll out pooling.
Experts disagree on the cutoff at which pooling stops being useful. The Centers for Disease Control and Prevention’s coronavirus test, which is used by most public health laboratories in the United States, stipulates that pooling shouldn’t be used when positivity rates exceed 10%.
But at Mayo Clinic, “we’d have to start to question it once prevalence goes above 2%, definitely above 5%,” Pritt said.
And prevalence isn’t the only factor at play. The more individual samples grouped, the more efficient the process gets.
But at some point, pooling’s perks hit an inflection point: A positive specimen can only get diluted so much before the coronavirus becomes undetectable. That means pooling will miss some people who harbor very low amounts of the virus.
“Are we going to cause harm if we miss them? I think that’s still a difficult question to answer,” Liesman said.
These people may be less likely to pass the virus to others and may be at lower risk of getting severely ill. But that’s no guarantee. Some might simply be early on in their infection.
Retesting positive pools also requires a large database of samples so that each member of the pool can be identified and crosschecked. And any sort of mislabeling errors, or crosscontamination between samples, could disrupt the entire workflow and risk an incorrect result.
Robots called liquid handlers, which can automatically batch samples, could be a game-changer for many labs. But given the current testing crisis, many of these pooling-capable machines are in extraordinarily high demand. At UC San Diego Health, Pride’s team has been waiting about two months for the arrival of three new liquid handling instruments. One finally arrived Monday.
To circumvent some of the issues, experts from disparate fields are cobbling together a few technical tricks. For example, in states, cities or even neighborhoods where coronavirus prevalence rates are high, less-hard-hit populations — “cold spots” — can still be plucked out and pooled, Abdalhamid said.
Every week, Abdalhamid of Nebraska’s public health lab checks the numbers, hoping for a sustained decline in local coronavirus cases. For months, the region’s positivity rate has stubbornly held around 20%.
But Abdalhamid hasn’t yet given up, he said: “Hopefully, when it hits 10 or below, we’ll get back to pooling right away.”