Can Pooled Testing for COVID-19 Help Solve Our Testing Woes?
by Meghna Agarwal, BS and Ameet R. Kini, MD, PhD
Six months after the emergence of COVID-19, testing delays still hamper our ability to contain the pandemic. In some cases test results have taken more than a week, at which point testing becomes pointless because it's too late to make effective interventions. To expand testing capacity, the FDA recently approved the use of pooled testing for the detection of the SARS-CoV-2. Will this step finally solve the backlog in testing and help our country reign in the pandemic?
Pooled testing has been in use since World War II, when the US government sought a method to screen new draftees for syphilis. Since then, it has been used by blood banks to screen for HIV and hepatitis C. In countries with limited resources, pooled testing allows labs to maximize their testing capacity when screening for diseases such as tuberculosis.
How does pooled testing work? Let’s say you have 100 people who need screening for COVID-19. If you combine samples from 4 people and use 1 test for that pool, you can screen all 100 people with 25 pooled tests. Assuming the infection rate in the tested population is low, you would expect most of the tests—say 20 of them—to be negative. The 5 positive tests represent samples from 20 people; the samples of these 20 people would then undergo individual testing to identify who is positive from each set. Using such a protocol would involve 45 tests to screen 100 people.
This method of testing increases daily testing numbers and reduces testing costs, potentially creating an effective option for schools, universities and workplaces where many people need screening in order to resume in-person activities, but where positivity rates among asymptomatic people may be low.
Pooled testing can be a very effective screening method, but it will not replace individual testing, and additional hurdles to improved testing remain in place. The shortage of testing supplies in many parts of the US has resulted in a major roadblock in testing. Pooled testing addresses this challenge by reducing use of certain supplies such as PCR reagents. However, the demand for other components such as nasal swabs and transport media will remain the same, so pooled testing does not address all the supply-chain problems.
Pooled testing represents an effective screening method in parts of the country with low community infection, generally less than 10% of the population. In current hot spots such as Arizona where over 20% of tests are returning positive, pooled testing would not be an effective surveillance tool because multiple additional confirmatory tests would be needed.
Additionally, pooled testing is only useful if the results are rapidly available. Since pooled testing typically involves an additional round of testing, results may be delayed unless tests can be performed in rapid succession by a laboratory. Another concern some have noted is the risk that diluting a positive sample could prevent the test from detecting the virus, resulting in a false negative test. However, since PCR strategies are very sensitive, false negatives are unlikely to be a major concern as long as the pools are not too large.
More sophisticated strategies for pooled testing that involve testing samples in grids or in multiple dimensions have been proposed. These strategies further increase the efficiency of pooled testing, conserving resources. One such strategy has been proposed for testing COVID-19 in Rwanda. However, the drawback of these strategies is that they require at least two rounds of testing, potentially delaying results. To overcome this issue, complex mathematical strategies have been proposed involving “Steiner triples” in which results can be obtained in a single round of testing by using multiple overlapping groups to detect positive samples. These strategies need further development and will likely require automation for successful execution; nevertheless, we believe such approaches are the most promising pathway for testing that will conserve resources and deliver fast results.
Pooled testing could provide a faster and efficient method to test large groups of lower risk people in certain situations. This strategy represents only part of an improved COVID-19 response. For pooling to be effective, testing has to be accompanied by proper interventions. Those who screen positive need to quarantine strictly and may need a place to stay away from home if they live with others at risk of infection. Workplaces and schools need to be flexible, and employees cannot be penalized for missing work to quarantine. Aggressive contact tracing is essential to prevent further spread of the virus. Since contact tracing and isolation are difficult to implement when the prevalence of the disease is high, the focus should remain on interventions such as distancing and masking to reduce disease burden. Once transmission rates are reduced, pooled testing can be an effective tool in keeping the pandemic under control and helping us regain a sense of normalcy in our lives.
Meghna Agarwal, BS is a Medical Student at the Loyola University Chicago Stritch School of Medicine and Ameet R. Kini, MD, PhD is a Professor of Pathology and Laboratory Medicine at the Loyola University Chicago Stritch School of Medicine.