For Quick Coronavirus Testing, Israel Turns to a Clever Algorithm
For Quick Coronavirus Testing, Israel Turns to a Clever Algorithm
BEERSHEBA, Israel — A team of three of Israeli scientists has pioneered a coronavirus testing procedure that they say is faster and more efficient than any now in use, testing samples in pools of as many as 48 people at once.
The Israeli government plans to roll out the new method in 12 labs across the country by October, anticipating that another wave of coronavirus infections could coincide with influenza season with potentially calamitous results.
“We’re doing everything we can in order to be ready,” said Ronen Walfisch, an engineer at the defense ministry who oversaw a pilot project to test the method’s efficacy. The method passed with flying colors, he said.
Moran Szwarcwort Cohen, who runs the virology lab at Rambam Health Care Campus in Haifa, said the new pooled-testing method, which was formally approved for clinical use by the Israeli health ministry on Tuesday, could allow schools, college campuses, businesses and airlines to clear whole groups of people far faster than has been possible until now.
“It’s a huge game-changer,” said Dr. Cohen, who was not involved in the new research.
Most pooling efforts elsewhere are relying on a simplistic approach developed to test World War II draftees for syphilis. That so-called Dorfman method, named for the economist who dreamed it up, calls for testing pools of samples from several people at once. If the pool tests negative, then all individuals are considered negative. If the pool tests positive, then additional samples from each individual must be retested to see which are positive.
The Israeli method, by contrast, is designed to only require one round of testing — a crucial savings in time, laboratory work flow and supplies.
It accomplishes that by building on a combinatorial algorithm that one of the three scientists, Noam Shental of the Open University of Israel, in Raanana, developed a decade ago to speed the detection of rare genetic mutations. It works much like error-detecting codes that filter out noise in telecommunications and computer science.
In a study published on Friday in the journal Science Advances, Dr. Shental and his colleagues, Tomer Hertz and Angel Porgador of Ben-Gurion University of the Negev, report that their method — called P-Best, for Pooling-Based Efficient SARS-CoV-2 Testing — successfully detected positives in pools of as many as 48 samples. The method accurately screened 1,115 health care workers with just 144 tests, the study found.
In one typical iteration, the Israeli team took samples of 384 people and divided them into 48 pools, so that each person’s sample wound up in a unique set of six pools.
Each of the 48 pools was then tested. If one person was positive for the virus, then each of the six pools containing that sample should test positive — resulting in a unique combination of positive pools revealing the identity of the person (or people) carrying the virus.
The algorithm optimizes the design of its pools according to the expected prevalence of the virus, making it possible to pinpoint all of the positive individuals in a batch, as long as the total number of positives does not sharply exceed the expected number.
Like all types of pooled testing, the usefulness of this method drops as a community’s “positivity rate” — the proportion of tests that come back positive — climbs.
But when positivity rates are lower, the Israeli method is dramatically more efficient than others, said Dr. Hertz. At an infection rate of 1 percent, he said, the new method is eight times as efficient as individual testing and nearly twice as efficient as an eight-sample Dorfman pool.
Israeli officials and researchers are working with an artificial-intelligence company to help cull samples that are likely to be positive, based on known hot spots, to keep positivity rates lower, Dr. Hertz said.
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Frequently Asked Questions
Updated August 17, 2020
Why does standing six feet away from others help?
- The coronavirus spreads primarily through droplets from your mouth and nose, especially when you cough or sneeze. The C.D.C., one of the organizations using that measure, bases its recommendation of six feet on the idea that most large droplets that people expel when they cough or sneeze will fall to the ground within six feet. But six feet has never been a magic number that guarantees complete protection. Sneezes, for instance, can launch droplets a lot farther than six feet, according to a recent study. It’s a rule of thumb: You should be safest standing six feet apart outside, especially when it’s windy. But keep a mask on at all times, even when you think you’re far enough apart.
I have antibodies. Am I now immune?
- As of right now, that seems likely, for at least several months. There have been frightening accounts of people suffering what seems to be a second bout of Covid-19. But experts say these patients may have a drawn-out course of infection, with the virus taking a slow toll weeks to months after initial exposure. People infected with the coronavirus typically produce immune molecules called antibodies, which are protective proteins made in response to an infection. These antibodies may last in the body only two to three months, which may seem worrisome, but that’s perfectly normal after an acute infection subsides, said Dr. Michael Mina, an immunologist at Harvard University. It may be possible to get the coronavirus again, but it’s highly unlikely that it would be possible in a short window of time from initial infection or make people sicker the second time.
I’m a small-business owner. Can I get relief?
- The stimulus bills enacted in March offer help for the millions of American small businesses. Those eligible for aid are businesses and nonprofit organizations with fewer than 500 workers, including sole proprietorships, independent contractors and freelancers. Some larger companies in some industries are also eligible. The help being offered, which is being managed by the Small Business Administration, includes the Paycheck Protection Program and the Economic Injury Disaster Loan program. But lots of folks have not yet seen payouts. Even those who have received help are confused: The rules are draconian, and some are stuck sitting on money they don’t know how to use. Many small-business owners are getting less than they expected or not hearing anything at all.
What are my rights if I am worried about going back to work?
What is school going to look like in September?
- It is unlikely that many schools will return to a normal schedule this fall, requiring the grind of online learning, makeshift child care and stunted workdays to continue. California’s two largest public school districts — Los Angeles and San Diego — said on July 13, that instruction will be remote-only in the fall, citing concerns that surging coronavirus infections in their areas pose too dire a risk for students and teachers. Together, the two districts enroll some 825,000 students. They are the largest in the country so far to abandon plans for even a partial physical return to classrooms when they reopen in August. For other districts, the solution won’t be an all-or-nothing approach. Many systems, including the nation’s largest, New York City, are devising hybrid plans that involve spending some days in classrooms and other days online. There’s no national policy on this yet, so check with your municipal school system regularly to see what is happening in your community.
A frequent concern raised about pooled testing is that samples will be diluted, causing a loss of sensitivity that could result in false negatives. But Dr. Shental said the new method was effective even with low viral loads because each sample is tested in multiple pools.
Israel is in the grip of a rough second wave of the pandemic, and many expect that it will only be brought under control by reimposing a nationwide lockdown. Because of delays in purchasing the sophisticated pipetting robots necessary to run the new method quickly, officials said they expect it will only kick in when that next lockdown is eased.
The three scientists who devised the method have formed a company, Poold Diagnostics, and are looking to bring their algorithm to labs in the United States. Michael S. Lebowitz, chief science officer at 20/20 GeneSystems, in Rockville, Md., which has plunged into the Covid-19 testing market, said it was in talks with Poold to file a joint application to the Food and Drug Administration for emergency authorization to try out its method.
He said the method could be enormously useful in getting businesses or college athletic programs back up and running and ensuring that their populations remain healthy. “The ideal situation is getting results in 24 to 48 hours,” he said. “If you can get compression of about eightfold, you’re now running many fewer samples.”
The inspiration for the Israeli method came from Dr. Shental’s mother. A few years ago, he said, she attended a lecture he gave to an audience of nonscientists in which he described his earlier research about using pooled testing for rare birth defects, and urged that it be made more widely available. As the coronavirus pandemic spread this spring, she asked him if that old algorithm might be deployed to test for Covid-19.
But Dr. Shental’s head was elsewhere: He had not worked with group testing in years, and was instead focused on research that got him on the cover of the journal Science in late May, in which he established associations between certain types of bacteria and certain kinds of tumors.
“I was dismissive of her at first,” Dr. Shental said, smiling sheepishly. “But when I was driving home, I realized it could work.”
Dr. Shental called his best friend, Dr. Hertz — the two got their Ph.D.’s together — and within two days, Dr. Porgador, who has since been named Ben-Gurion University’s dean of the health sciences, had set up an experiment using samples from Soroka Hospital across the street. A short time later, Ben-Gurion’s president, Daniel Chamovitz, who had solicited suggestions for how to fight the pandemic with a promise to fund the best ones, found $150,000 to buy an advanced pipetting robot to try out their idea.