False-negative tests could pit us against a “less visible second wave of infection,” according to the authors of a new study published in Mayo Clinic Proceedings.

As our ability to screen for COVID-19 increases, medical personnel and health officials have to keep in mind that tests aren’t perfect, and that false results can have an effect on our ability to contain the pandemic. The sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR) testing, our main way of identifying infected patients, has not been clearly or consistently reported in the literature, but even at high accuracy rates, large numbers of false-negative results are likely.

“RT-PCR testing is most useful when it is positive,” says Dr. Sampathkumar, an infectious diseases specialist at Mayo Clinic and a study co-author.

“It is less useful in ruling out COVID-19. A negative test often does not mean the person does not have the disease, and test results need to be considered in the context of patient characteristics and exposure.”

In broad lines, such tests can be used to detect the presence of the virus in a patient by copying all the DNA in a sample of their blood, multiplying everything, and then looking for bits of viral DNA. Unlike tests that look for antibodies in the blood, RT-PCR can detect the virus even before our bodies have begun to respond to it, which is an important ability. On the downside, they are less reliable, as a negative result simply means there was no viral DNA found in that sample; it could, theoretically, still be somewhere else in the body.

Even with sensitivity values as high as 90% (this value determines the test’s ability to detect the virus in an infected sample), the team argues we’d see a substantial number of false-positives. Such patients are still able to pass the virus on, even if they’re asymptomatic.

“In California, estimates say the rate of COVID-19 infection may exceed 50% by mid-May 2020,” Dr Sampathkumar says.

“With a population of 40 million people, 2 million false-negative results would be expected in California with comprehensive testing. Even if only 1% of the population was tested, 20,000 false-negative results would be expected.”

Healthcare personnel are one of the most exposed groups in this pandemic. If even just 10% of all those involved in providing direct patient care in the US got infected, although this is far below current predictions the team explains, we could be looking at over 40,000 false-negatives in this field alone.

Given that current guidelines from the Centers for Disease Control and Prevention (CDC) call for asymptomatic health care workers who tested negative for the virus to return to clinical care, this could help spread the disease even more rapidly inside hospitals, according to the team.

The authors recommend continued strict adherence to physical distancing, hand-washing, surface disinfection, and other preventive measures for everyone, while working on the “development of highly sensitive tests or combinations of tests” to allow us to confidently tell sick and healthy individuals apart.

The paper “COVID-19 Testing: The Threat of False-Negative Results” has been published in the journal pre-proof Mayo Clinic Proceedings.