The Israeli ‘Pooling’ Method That Could Rapidly Expand COVID-19 Testing

A method of testing for the novel coronavirus refined in Israeli labs could dramatically increase the speed at which tests for the virus can be performed. If the technique known as pooling works on a larger scale it would open up the potential for mass testing. Combined with other sound policies, mass testing could efficiently isolate and treat infected individuals, relieving some of the burden on overwhelmed hospitals by keeping healthy people out while allowing limited medical supplies to go to those who need them most.

Drawing on experience with a “pooling” technique used in Africa to test blood for HIV, microbiologists at the Technion-Israel Institute of Technology collaborating with experts at Rambam Medical Center in Haifa, adapted the method to test for the novel coronavirus, which causes the disease COVID-19. Most testing around the world is currently being conducted one person at a time, a process that is both time consuming and places a heavy tax on critical protective gear that hospital workers wear while administering the tests. The Israeli pooling protocol makes it possible to test up to 64 people at the same time.

“Only in those rare cases in which the joint sample is found to be positive will we have to test each sample individually,” said Dr. Yuval Gefen, director of Rambam’s clinical microbiology laboratory.

Currently the protocol is designed as a molecular test to determine whether or not an individual has been infected with coronavirus, but according to a researcher at Technion’s Biology Faculty, it might also be possible to apply the protocol to blood testing. Blood tests, also known as serological tests, are used to detect antibodies produced by the immune system that could be the key to unlocking how certain people develop an immunity to COVID-19. The Israeli pooling test methodology can theoretically be applied to serological tests, the researcher at Technion said, but requires calibration and careful testing to see if it works.

Right now, testing people for COVID-19 is one of the critical bottlenecks preventing rapid monitoring, control, and treatment of those who carry the potentially deadly virus. At present, only those Israelis displaying symptoms associated with the disease, or people who have been in contact with the infected, or who returned from abroad have been tested; the current testing figure has now reached around 3,000 per day in Israel. Yet with lab personnel joining those infected and being put into isolation, virology lab facilities have been overwhelmed.

After initially balking over mass testing of those without symptoms and realizing the threat of a near-economic shutdown, Prime Minister Benjamin Netanyahu approved testing for Israelis without symptoms or those who have not had direct contact with the infected.

In the United States, with a population many times the size of Israel’s spread out over a vastly larger geographical area, it is much more difficult to isolate and trace the activities and contacts of infected individuals—and it is altogether impossible to do so with the testing capacity that is now available. The result is that in hard-hit states like New York, which had 30,611 confirmed cases on Wednesday, eight to 10 times more than in the rest of the United States, even people who display symptoms of COVID-19 aren’t necessarily eligible for tests.

Professor Itamar Grotto, the associate director-general of Israel’s Health Ministry in Jerusalem who was informed about the research from its onset, confirmed to Tablet that the pooling technique could be implemented quickly for testing larger populations. This would gradually free the healthy to go back to work, said Grotto, who in 2018 was elected to the prestigious executive board of the World Health Organization.

COVID-19 has been diagnosed with polymerase chain reaction (PCR) testing (a lab technique that creates millions of copies of a particular section of DNA) on pairs of samples from individual people’s epithelial cells in the mouth and mucus from the nose. This test examines the presence of a unique genetic sequence of the virus, and takes several hours to deliver answers.

Professor Roy Kishony, head of the research group in the Technion’s Biology Faculty, explained: “Even when we conducted a joint examination of 64 samples in which only one was a positive carrier, the system identified that there was a positive sample,” he said. “Although there are some logistical challenges in implementing the method, we expect that it will greatly increase the volume of samples tested per day so that we can identify the asymptomatic carriers. This approach should reduce the chance of infection and flatten the infection curve.”

According to Kishony, the testing could start immediately. “The only hurdle is willingness to do it,” he said. “All virology lab workers would know how to do it, I was told. [In Israel] the hurdle is a decision that not only people with symptoms would be tested but that testing would be expanded to those without symptoms. That would require spending more money on testing kits.”

Interest in the new testing method already appears to be coming from various affected regions across the world. “After our discovery was announced, we immediately received queries from around the world, including Europe, Africa and the Americas,” said Kishony, who is also a visiting faculty member at the department of systems biology at Harvard Medical School.

Dr. Idan Yelin, a researcher in Kishony’s lab, added that “the pooling idea is simple, but we had to see if it works. We worked superfast in this crisis, as virology labs are very overburdened. We sent genuine RNA samples to the Technion lab that had been taken from people who were confirmed infected with the virus as well as people who were negative for it. We protected ourselves as if all the samples were positive and mixed one positive sample with up to 63 negatives. We saw that even though the positive sample was very diluted, it could be detected among the negative ones. Molecular biology has a great power to identify a small number of molecules,” he stressed.

“If none of the 64 is found to be positive in mass testing, isolation measures can be relaxed and those who are ‘clean’ can be freed; if one or a few are positive, all have to be isolated,” Yelin explained. “Many scientists around the world probably thought of the pooling idea before, but they didn’t try it. We did it fast and right. With the proper controls. Lab people anywhere will know exactly how to accomplish it.”

Yelin said that his lab has been overwhelmed by requests from researchers and doctors who work in the field in countries including Romania, Switzerland, Peru, and the United States, where they received a request from Minnesota to receive the protocol, which was quickly provided.

Numerous teams abroad, Yelin said, are trying the protocol in their lab systems and preparing to implement it in the coming days and weeks. It takes time, as each country and facility is different. Israel’s Health Ministry is now in the process of examining the technique, he said, with the aim of implementing it in the field.

Asked to comment on the Israeli discovery, Higginson professor of physiology and medicine at Harvard Medical School Jeffrey Flier, a former dean of the school, said: “I suspect the technical claims are correct. Someone would need to model this to determine how much testing benefit would derive from first testing pooled specimens and only retesting individually if the pool is positive. Likely this would produce greater benefit for mass screening at a time and place where the great majority are negative. This might save some testing resources, at a time when they are limited.”

Technion’s president, professor Uri Sivan, commented: “This experiment … is complex, and under normal circumstances, it would take months.” But in this case, “the initial experiment was completed in less than four days,” he said.

On Wednesday, the governor of Nebraska, Pete Ricketts, announced that the U.S. state had begun using its own “pooling” method for COVID-19 tests. At present, the method used in Nebraska appears to allow for six samples to be tested simultaneously, compared to an upper limit of 64 using the Israeli method.