Pooling samples could accelerate new coronavirus testing

Virologists from Germany have shown that combining samples and only testing individual samples if there is a positive result for the group could massively increase the capacity for coronavirus testing.

Testing has been a major limiting factor in the response to the COVID-19 pandemic.

Healthcare systems across the world have been struggling to cope with the demand for testing, with many countries having insufficient capacity even to test healthcare workers. Laboratory infrastructure is stretched and, in some cases, completely overwhelmed by the pandemic.

Scientists from Germany, which has had an admirable testing capacity, have published details of a testing strategy that they say could massively increase capacity in laboratories around the world.

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The strategy involves pooling samples from multiple people and only testing individual samples if the result from the group test is positive. This could potentially save thousands of unnecessary tests.

The details now appear in The Lancet Infectious Diseases.

Why is testing so important?

Testing is an essential part of the response to the pandemic. Germany’s high testing rates have been linked to the country’s lower death toll. Around 7,569 people have died of COVID-19 in Germany, compared with 31,930 in the United Kingdom and 30,560 in Italy. This is despite Germany having a larger population than both of these countries.

Knowing who has the virus is critical in preventing them from coming into contact with others, particularly among people who are most at risk, such as older adults and those with serious illnesses.

This is not simply a case of isolating people with symptoms, however, as people can carry the virus without experiencing any symptoms at all. People can also be contagious before the onset of symptoms — in fact, viral load is at its highest around a day before any symptoms appear — making diagnostic tests essential.

“Prevention is only possible if we use large-scale testing to identify asymptomatic persons and thus avert infection of the most vulnerable,” explains senior study author Prof. Sigrun Smola, director of the Institute of Virology at Saarland University Medical Center in Germany.

How does testing work?

To test for a SARS-CoV-2 infection, scientists take swabs from the nose or back of the throat to check for genetic material from the virus. This may sound simple, but it involves a number of time consuming steps in the laboratory, which can take several hours.

To speed things up, the scientists behind the new study took inspiration from blood banks, which often use a technique called sample pooling.

The approach works by combining a number of samples before performing the experimental workup, and only testing individual samples if the group sample has a positive result. This can prevent many unnecessary individual tests.

The scientists say that the technique is easy to perform and can expand the capacity of laboratories when “large numbers of asymptomatic people need to be screened.”

Work on the approach began in March, when the researchers started pooling samples from medical staff without symptoms of COVID-19. They tested a range of pool sizes, starting from four samples to 30 samples per pool.

The test was so sensitive that the team could combine samples from 30 different people in one test tube.

“Even if only one person in that group of 30 was infected, we still obtained a positive result for the pooled test. If a pool had a positive result, we then conducted a second phase of testing on the individual samples to identify the infected person or persons.”

– Prof. Sigrun Smola

After testing 1,191 samples in this way, only 267 tests were necessary to identify the 23 people who had coronavirus. In a normal testing format, laboratories would need to test all the samples individually. This approach, therefore, saved over 900 tests.

“If the rate of infection is low and if many of the pools are negative, this can save significant numbers of test kits and increase the test capacity of the existing infrastructure” adds Prof. Smola.

Care home trials

Thanks to the success of these experiments, various nursing and residential care homes — which house some of the people at highest risk — are now enrolling in the program. In fact, at the time of writing, 131 homes in Saarland have enrolled in the screening program, which will test both residents and staff. That comes to around 22,000 people in total.

Prof. Smola says that the team is also getting requests for help from elsewhere.

“We have also received numerous urgent inquiries from hospitals in Germany and abroad, as testing capacity limitations are proving to be a critical issue at this moment.”

As a final note, it is important to caution that although this method provides “sufficient diagnostic accuracy,” the scientists do say that it might not detect “borderline positive” samples in large pools.

A person might have a “borderline positive” result if they contracted the infection 2 or 3 weeks before undergoing the test and are now recovering.

To avoid missing diagnoses such as these, the scientists recommend choosing an appropriate pool size for different infection scenarios and pooling fewer samples if there may be borderline cases in the cohort.

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