By Barbara Caceres
Published September 29, 2020 | Medicine, Public Health
Health experts now say that PCR testing for SARS-CoV-2, the virus associated with the illness COVID-19, is too sensitive and needs to be adjusted to rule out people who have insignificant amounts of the virus in their system.1 The test’s threshold is so high that it detects people with the live virus as well as those with a few genetic fragments left over from a past infection that no longer poses a risk. It’s like finding a hair in a room after a person left it, says Michael Mina, MD, an epidemiologist at the Harvard T.H. Chan School of Public Health.2
In three sets of testing data that include cycle thresholds compiled by officials in Massachusetts, New York and Nevada, up to 90 percent of people testing positive carried barely any virus, a review by The New York Times found.3
Manufacturers and Labs Set Criteria for Positive COVID-19 Test Results
The reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test used to identify those people infected with the SARS-CoV-2 virus uses a nasal swab to collect RNA from deep within the nasal cavity of the individual being tested. The RNA is reverse transcribed into DNA and amplified through 40 or more cycles, or until virus is detected.4 The result is reported as a simple “yes” or “no” answer to the question of whether someone is infected.
The U.S. Food and Drug Administration (FDA) officials state they do not specify the cycle threshold ranges used to determine who is positive, and that commercial manufacturers and laboratories set their own threshold ranges.5
PCR Test Threshold for COVID-19 Positivity Is Too Sensitive
Any test with a cycle threshold (CT) above 35 is too sensitive, says Juliet Morrison, PhD, a virologist at the University of California, Riverside. “I’m shocked that people would think that 40 [cycles] could represent a positive.” A more reasonable cutoff would be 30 to 35, she added. Dr. Mina said he would set the figure at 30, or even less. Those changes would mean the amount of genetic material in a patient’s sample would have to be 100-fold to 1,000-fold that of the current standard for the test to return a positive result worth acting on.6
The CDC’s own calculations suggest that it is extremely difficult to detect any live virus in a sample above a threshold of 33 cycles.7
“We’ve been using one type of data for everything, and that is just plus or minus—that’s all,” Dr. Mina said. “We’re using that for clinical diagnostics, for public health, for policy decision-making.” But “yes” or “no” isn’t good enough, he added. It’s the amount of virus that should dictate the infected patient’s next steps. “It’s really irresponsible, I think, to forgo the recognition that this is a quantitative issue,” Dr. Mina said.8
The number of people with positive results who aren’t infectious is particularly concerning, said Scott Becker, executive director of the Association of Public Health Laboratories. “That worries me a lot, just because it’s so high,” he said.9
SARS-CoV-2 Positive Case Numbers Drop When Cycle Threshold is Adjusted, Removing Need for Contact Tracing
Officials at the Wadsworth Center, New York’s state lab, have access to CT values from tests they have processed, and analyzed their numbers at The Times’s request. In July, the lab identified 872 positive tests, based on a threshold of 40 cycles. With a cutoff of 35 cycles, about 43 percent of those tests would no longer qualify as positive. About 63 percent would no longer be judged positive if the cycles were limited to 30.