If the country wants to crank up its Covid-19 testing capacity into the millions — the range that could be required for safer reopenings of businesses and universities — experts say it’s time to ramp up a technique known as “pool testing.”
It’s a simple construct: combine — or pool — samples from multiple people and test them as a group for the coronavirus. It’s a way to dramatically and efficiently increase volume, to churn through what you expect to be a lot of negative samples at a fast clip.
“Pooling would give us the capacity to go from a half a million tests a day to potentially 5 million individuals tested per day,” Deborah Birx, who is helping lead the White House’s coronavirus response, told an American Society for Microbiology virtual conference this week.
Despite progress after a notoriously fumbled rollout, the U.S. testing landscape continues to face challenges. There remain shortages of swabs and reagents; machines can’t keep up with demand as local outbreaks increase; and some places lack adequate testing sites. Those will have to be addressed in order for testing capacity to expand to the levels experts say is necessary to allow people to return to work and keep the virus at bay.
Pool testing isn’t meant to verify whether or not a person has Covid-19, the way an individual diagnostic test does.
Rather, it’s part of a broader disease surveillance strategy, one that allows for regular screening of people who are not experiencing Covid-19 symptoms. Testing asymptomatic people is important because a large portion of people with the coronavirus either show no symptoms or take a few days to start feeling sick, but they can still spread the virus.
Take a warehouse with 100 employees. Every so often (experts are still weighing how frequently this testing should occur), the company could test the staff, and instead of running 100 separate analyses, it could group 10 samples into a pool and only run 10 analyses.
“You could test everyone as they walk into the door,” said Paul Sax, an infectious disease specialist at Brigham and Women’s Hospital, who has written about the challenges of returning to work during the pandemic.
If one of those pools came back positive, those 10 employees could be retested individually to see who was infected and could remain out of work in the interim. The 90 other employees, in the pools that tested negative, wouldn’t need to be retested. The goal would be to try to detect a case before the person potentially spread the coronavirus to others. Scientists are increasingly finding that such large-scale superspreading events at workplaces, restaurants and bars, and places of worship are driving a large amount of transmission.
Identifying asymptomatic and presymptomatic people could also enable a more aggressive contact tracing approach, Birx said in her talk this week.
Beyond workplaces and universities, regularly testing groups of people in a given community could also provide a harbinger of increased spread if suddenly a higher portion of pools came back positive. That could serve as an early signal to local officials that they may need to increase distancing strategies, before hospitalizations started to increase.
“It allows you to test more frequently in a population that may have a low prevalence of disease,” said Benjamin Pinsky, the medical director of Stanford’s Clinical Virology Laboratory, who has led pooling studies for the coronavirus. “That would allow you to test a lot of negatives, but also identify individuals who are then infected, before they develop symptoms.”
As Pinsky noted, pooling only makes sense in places with low rates of Covid-19 where you expect the large majority of tests to be negative; otherwise, too many of the pools would come back positive for it to work as a useful surveillance tool.
“You wouldn’t want to be doing it right now in Texas, but you could do it in Massachusetts,” Sax said. Texas this week has been reporting record levels of new cases — several thousand each day; Massachusetts, meanwhile, reported 226 on Thursday and has been trending downward.
Pool testing relies on the same PCR technology as individual diagnostic tests. The number of people’s samples that can be grouped together depends on which machine is running the test, but scientists say that up to 10 samples could be pooled in some cases. (These are different from the rapid, point-of-care tests that researchers hope to roll out in the coming months. Results from pool testing could still take hours to days, depending on the demand on local labs.)
For all the advantages in efficiency that pooling offers, there is a downside: It increases the risk of a false negative. That is, if someone does have the virus, the viral level in that individual sample will be diluted when combined with other samples, perhaps to the point where the machine can no longer detect it.
“The goal is to increase the capacity of testing in a relatively straightforward fashion,” Pinsky said. “The caveat is that by pooling the sample, you’re going to reduce the sensitivity of the test.”
One way to compensate for that risk of false negatives is to conduct testing frequently, experts say.
The Food and Drug Administration recently released guidance describing what labs need to do to validate their pooling strategies and is sponsoring its own validation studies, Brett Giroir, an assistant health secretary who has served as the Trump administration’s point person for testing, said on a call with reporters this week.
As a chemist I did his with milk samples for pesticide residues in 1972. It is a simple math problem based on the limits of detection and the background levels, but accurate sampling and dilution are the main issues. I used the technique for samples from some areas, but not others because of the issues noted. With the variation in swabs and the consequences of being wrong, I would very, very carefully evaluate the methodology before using it for COVID. A quantitative method, as opposed to pass/fail, would be better suited, and it might be more useful for repetitive testing of the same individuals. If it was used in China and Germany, it should have applicability elsewhere.
Download the appropriate link. I chose …
Molecular Diagnostic Template for Laboratories …and searched the document for ‘pooling’.
Here is how pool testing should work. Everyone is swabbed with TWO swabs initially. First swab from each individual is added to a pool and tested for COVID. If the pool tests positive, then all the SECOND swabs from each individual that were collected initially get tested to find the individual(s) who are actually positive. This way you efficiently narrow down the actual positive cases without trying to bring people back in to re-test.
China and Germany have been doing this for months. Why hasn’t the US? Why is this still a discussion? Drawbacks other than sensitivity loss?
I’m interested as a school administrator. I want the staff at the school to be tested on a periodic basis before the official start of school in August.
A mathematical basis of pools testing has been published recently
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