Dealing With False Negative COVID-19 Test Results

Mass testing for coronavirus diseases 2019 (COVID-19) is believed to have played a role in mitigating the spread of the pandemic in countries like South Korea. In fact, plans for the United States to flatten the curve have called for millions of tests to be made available.

The US Food and Drug Administration (FDA) has issued more than 30 emergency use authorizations to date for various tests which detect SARS-CoV-2. Newly authorized tests include real time polymerase chain reaction (RT-PCR) diagnostics as well as serological assays.

The authors of a new commentary published in Mayo Clinic Proceedings explained that while positive results from these tests can be very helpful, negative COVID-19 test results may lead to a false sense of security. Clinicians are advised to use diagnostics, but to evaluate the full clinical picture in determining the proper diagnosis of patients who may have COVID-19.

The overall performance of SARS-CoV-2 RT-PCR tests varies between specific iterations, and sensitivity values have not been clearly articulated in the literature so far. The authors noted that in China early RT-PCRs performed poorly.

Early reports cited a possible test sensitivity rate of 70%. If test sensitivity is as high as even 90%, the scale of testing in the United States and globally still presents a sizable burden of false negatives.

If estimates of the COVID-19 infection rate in California are correct and exceed 50%, testing all 40 million people in the state would yield about 2 million false-negative results. If 1% of the population is tested, at least 20,000 false-negative results could be expected.

The impact of a 90% test sensitivity on health care personnel could also be substantial. To illustrate this, the authors pointed out that if only 10% of the more than 4 million health care workers providing direct patient care were infected with COVID-19, over 40,000 false-negative results could be expected from universal testing.

The results suggest that personal protective equipment should be available for all health care workers, including those working with suspected COVID-19 patients who have tested negative.

The authors also suggest that highly sensitive and specific combinations of tests could be devised. Current tests could also be improved upon, or at least better understood in terms of sensitivity.

Clinicians can also develop risk stratification for suspected COVID-19 patients. A negative result would be more reassuring in the clinical circumstance of a patient at low risk for severe infection than an older patient with underlying health conditions.

The current situation risks a "less visible second wave of infection from people with false-negative test results," study author Priya Sampathkumar, MD, an infectious diseases specialist at Mayo Clinic, said in a press release.