CEO SUMMARY: Some experts on testing strategies support pooled testing because this method may support reopening by schools and businesses and thus bring the economy back. But other experts have raised questions about this strategy. Rules from the federal Centers for Medicare and Medicaid Services say pooled testing is not diagnostic and so any lab can do these tests. But CMS also says any positive result from a pool would require retesting, which would be diagnostic, causing delays.
IN CONTRAST TO POPULATION SURVEILLANCE, USE OF THE POOLED TESTING METHOD would signal a significant change in how testing for SARS-CoV-2 has been performed in the United States since February.
At the beginning of the coronavirus pandemic in the United States, testing with the reverse transcription polymerase chain reaction (RT-PCR) method was limited due to low availability. Therefore, the RT-PCR assay was used almost exclusively for testing symptomatic patients to determine proper hospital isolation and other protocols. Each specimen was tested with one test procedure.
Individual Risk Assessment
As the SARS-CoV-2 virus spread, health officials advocated for additional testing for surveillance and to trace the source of spread resulting in even greater demands for test capacity. The current national focus to screen large numbers of people as part of the effort to reopen commerce and society will require even larger numbers of tests, further stretching capacity.
Aggregating patient specimens and testing by a pooled strategy could provide for greater national COVID-19 test capacity. Pooled testing is designed to conserve laboratory resources—including test reagents and lab personnel time. It has the potential to increase the number of individuals who can be tested and support the idea of safely reopening schools, offices, and other places of work. As result, pooling tests has the support of top experts on the White House Coronavirus Task Force.
But other testing experts have expressed doubts about pooled testing. (See sidebar below.) Those in favor include Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), who said he and other federal health officials were in discussions about how to increase pooled testing for COVID-19. “We hope to get this off the ground as soon as possible,” he commented in an interview with The New York Times. NIAID is a division of the National Institutes of Health.
For months, Fauci has recommended this strategy to federal officials without much success. But as the number of virus infections rose steadily in recent weeks, those officials have become more open to the idea, he added.
Admiral Brett P. Giroir, MD, Deputy Secretary of the federal Department of Health and Human Services and the head of testing for the task force, said he expected a pooled COVID-19 testing program to be running by the end of the summer. As students return to universities, “pooling will be very mature,” he said, the Times reported. “My assessment is that the data is very strong,” he added.
Manoj Jain, MD, an Adjunct Professor and infectious disease physician at the Rollins School of Public Health at Emory University, said, “I’m just wondering why the federal government does not mandate now that this be done to preserve the testing capacity. We really haven’t learned from our counterparts in Europe and Asia” who have used pooled testing, such as in China, Germany, Israel, and Thailand, the Times reported.
Steven H. Hinrichs, MD, Chair of the Department of Pathology and Microbiology at the University of Nebraska Medical Center, agreed, saying, “If you want to bring students back to school and you need to test everyone, you can’t afford to perform the tests individually. Doing that would totally use up all the COVID-19 reagents, tests, and supplies. Therefore, you need to use a group testing strategy by pools, but you have to do so correctly.
Individual Risk Assessment
“We need to distinguish between individual risk assessment and public health screening,” Hinrichs explained. “We’d like to see pooled testing used for low-risk public health assessment, meaning population risk assessment instead of symptomatic individual treatment assessment.”
Hinrichs and colleagues from the University of Nebraska Medical Centerand the University of Nebraska-Lincoln published research in April, “Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources,” in the American Journal of Clinical Pathology.
Other important questions to consider about pooled COVID-19 testing are the limits of detection and the sensitivity and specificity levels of the assay,
Hinrichs added. “Another issue is the specimen-collection method,” he continued. “Everybody wants to say that every type of specimen is the same and unfortunately they’re not. In our experience, the nasopharyngeal swab is a much better specimen collection method than an oral swab or a saliva swab, depending upon the stage of infection or number of days of infection.”
Public Health Officials Raise Questions About Use of Pooled Testing for COVID-19
ON JUNE 16, THE FOOD AND DRUG ADMINISTRATION outlined the steps test manufacturers would use to get their SARS-CoV-2 molecular RT-PCR tests authorized for broad screening of asymptomatic individuals using pooled testing.
Three days later, the federal Centers for Medicare and Medicaid Services (CMS) said it did not consider pooled testing to be diagnostic. Therefore, CMS said, any private or academic lab could use this method to screen patients for COVID-19 and reveal the grouped results from a pool to those patients who contributed samples.
But under CMS’ rules for diagnostic testing, if a batch tests positive, each patient’s sample would need to be retested and that retest would be diagnostic.
Therefore, that second COVID-19 test would need to be done in a CLIA-certified lab, CMS said. Sending those repeat tests out for diagnosis would add a delay of several days, experts told The New York Times.
Kelly Wroblewski, Director, Infectious Disease Programs, at the Association of Public Health Laboratories, told the Times that a delay raises questions about the value of pooled COVID-19 testing. “That’s where I think we probably start to disagree with pooling as a strategy,” Wroblewski said. Since the FDA and CMS require diagnostic tests for COVID-19 to be done at CLIA-certified labs, a change in policy to facilitate pooled testing needs further discussion, she added.
Concerns about Delays
In response to concerns about delays, Steven H. Hinrichs, MD, Chair of the Department of Pathology and Microbiology at the University of Nebraska Medical Center, offered a clarification.
“There is some confusion about the test protocol,” he explained. “Our method uses the pooled approach to perform the screen, and only an aliquot of each of the original specimen is pooled, not the entire sample. Therefore, if a pool is found to be positive, each of the original samples in the pool is retested individually.
“There is no need to send the pools to a separate lab or to recollect the specimen from the subject,” he said. “In our experience, the result is not delayed in reporting to the individual or the health authority.”
Wroblewski had another concern, saying pooled testing is unlikely to be useful at most state labs. In most states, infection rates are at 15% or more, which is above the recommended 10% level of prevalence for pooled testing. “I don’t think it’s going to solve all our problems,” she told the Times.
Test and Isolate
Another expert who raised questions was former CDC Director Thomas R. Frieden, MD, who said any COVID-19 testing strategy was unlikely to succeed without isolation of those tested until results are available. Anyone who is infected needs to be isolated away from the home, he added.
“What I find both frustrating and dangerous is the consistent failure to understand that testing, in and of itself, pooled or not, does little or no good,” Frieden told the Times in an email. “What good is testing if the results take four days to come back and infectious people aren’t isolated in the interim? What good is COVID-19 testing if contact tracing doesn’t identify and warn exposed people quickly?”
Nebraska Lab Gets First Pooled Test with EUA
TODAY, CLINICAL LABS HAVE AT LEAST ONE COVID-19 TEST with an emergency use authorization (EUA) that can be employed for pooled testing.
In late June, Steven H. Hinrichs, MD, Chair of the Department of Pathology and Microbiology at the University of Nebraska Medical Center (UNMC) was aware of only one COVID-19 assay that obtained an FDA EUA for pooled testing.
That assay was adapted from a lab-developed test—the NEcov19 RT-PCR Assay—that the UNMC sent to the FDA for an emergency use authorization in March.
An FDA test with an EUA must be adapted, or bridged, to be used for pooled testing, Hinrichs explained. The FDA allowed UNMC to write a bridging EUA based on its NEcov10 RT-PCR Assay.
“When a manufacturer or lab has an EUA for a SARS-CoV-2 test, and it provides data on how the test works, the FDA says that EUA can then be modified with a bridge,” he said. “So, the data about the pooled testing bridges to the original EUA and then the FDA can accept it or not.”
Contact Steven H. Hinrichs, MD, at 402-559-7255 or email@example.com.