Pooling Samples to Increase SARS-CoV-2 Testing

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© Indian Institute of Science 2020.

Pooling Samples to Increase SARS‑CoV‑2 Testing

Manoj Gopalkrishnan1* and Sandeep Krishna2 Abstract | As SARS-CoV-2 continues to propagate around the world, it is becoming increasingly important to scale up testing. This is necessary both at the individual level, to inform diagnosis, treatment and contract tracing, as well as at the population level to inform policies to control spread of the infection. The gold-standard RT-qPCR test for the virus is relatively expensive and takes time, so combining multiple samples into “pools” that are tested together has emerged as a useful way to test many individuals with less than one test per person. Here, we describe the basic idea behind pooling of samples and different methods for reconstructing the result for each individual from the test of pooled sam‑ ples. The methods range from simple pooling, where each pool is disjoint from the other, to more complex combinatorial pooling where each sam‑ ple is split into multiple pools and each pool has a specified combination of samples. We describe efforts to validate these testing methods clini‑ cally and the potential advantages of the combinatorial pooling method named Tapestry Pooling that relies on compressed sensing techniques. You may have heard of this puzzle about identifying a fake coin: You have eight Rs. 1 coins. Real coins weigh 10 g each, but you are told that one of the coins is fake and weighs less than the others. Using a simple weighing machine, on which you can place some coins and read out their total weight, what is the least number of weighings in which you can locate the fake coin? You could check each coin one by one, which could need upto seven weighings if you’re unlucky (see Fig. 1a). Another way would be to ‘pool’ the coins into two sets of four coins and then weigh one pool and then the next. One of these pools will weigh 40 g and the other less, so you will already know that four coins are real. Then you could split the coins in the second pool into two each and weigh them, and then finally test each coin from the group of 2 that weighed less than 20 g. This would take three weighings to identify the fake coin (see Fig. 1b). A similar idea can be used to pool samples to test for the virus SARS-CoV-2 which causes Covid-19. Instead of coins, we have samples taken from the nose, throat or saliva of people we are

J. Indian Inst. Sci. | VOL xxx:x | xxx–xxx 2020 | journal.iisc.ernet.in

testing. Instead of weighing them, we use an RTqPCR assay to test for the presence of the virus. Suppose we had samples from eight people of whom one was infected. We could have tested each sample individually. In the worst case we need seven tests to identify the infected person. But if we pooled the samples into sets of four, and then sets of two, as with the coins, then we would need a mere three tests! Pooling samples can thus save tests. This can save time, reagents and plastics, manpower, money, and most importantly— by enabling more testing—lives. Testing for SAR