Harlan M. Krumholz, M.D.,
The New York Times Company
April 1, 2020
You had some exposures that may put you at risk for coronavirus. A few days later you come down with a bad cough yourself and feel a little short of breath and really tired. You take your temperature: 101 degrees. A fever.
You suspect you might have COVID-19, the disease caused by the novel coronavirus. The days roll into each other and your doctor urges you to stay home unless your condition worsens. You feel pretty bad, though, and finally get an appointment.
They test you for influenza by sticking a swab far up your nose and you are told the test came back negative, you don’t have flu. They tell you they are saving the COVID-19 tests for those who are even worse off than you are. You go home with a prescription for antibiotics, possibly because they don’t know what else to do, and read about celebrities who are testing positive but don’t seem so sick.
A couple of days later, still with fevers, you go back, and the doctors relent and test you for SARS-CoV-2, the virus that causes COVID-19. They again stick something up your nose to what feels like the bottom of your eyeball.
They tell you that the results will be available in a couple of days and you go home and wait. Finally, the results come back and you are told you do not have COVID-19. Now what?
This is a real patient’s story. In fact, it is a lot of people’s story — at least some version of it. Across the world, people with signs and symptoms of COVID-19 are testing negative and wondering what it means. They are not showing up in the statistics and they are left in limbo about what to do next.
The problem may be with the test. Current coronavirus tests may have a particularly high rate of missing infections. The good news is that the tests appear to be highly specific: If your test comes back positive, it is almost certain you have the infection.
The most common test to detect the coronavirus involves a process known as reverse transcription polymerase chain reaction, or RT-PCR, a jumble of words that describes a method capable of detecting virus particles that are generally present in respiratory secretions during the beginning of an infection. From a technical standpoint, under ideal conditions, these tests can detect small amounts of viral RNA.
In the real world, though, the experience can be quite different and the virus can be missed. The best the Centers for Disease Control and Prevention can say is that if you test negative, “you probably were not infected at the time your specimen was collected.” The key word there is “probably.”
False-negative test results — tests that indicate you are not infected, when you are — seem to be uncomfortably common. Increasingly, and disturbingly, I hear a growing number of anecdotal stories from my fellow doctors of patients testing negative for coronavirus and then testing positive — or people who are almost certainly infected who are testing negative.
Unfortunately, we have very little public data on the false-negative rate for these tests in clinical practice. Research coming out of China indicates that the false-negative rate may be around 30%. Some of my colleagues, experts in laboratory medicine, express concerns the false-negative rate in this country could be even higher.
There are many reasons a test would be falsely negative under real-life conditions. Perhaps the sampling is inadequate. A common technique requires the collection of nasal secretions far back in the nose — and then rotating the swab several times. That is not an easy procedure to perform or for patients to tolerate. Other possible causes of false negative results are related to laboratory techniques and the substances used in the tests.
So, where does that leave us? Even with more testing, we are likely to be underestimating the spread of the virus. For now, we should assume that anyone could be carrying the virus. If you have had likely exposures and symptoms suggest COVID-19 infection, you probably have it — even if your test is negative. We should all continue to practice the behaviors — rigorous hand washing, not touching the face, social distancing — that impede its spread. And we need better information about the performance of these tests — including any new tests that are introduced — in the real world.
Even as better tests emerge, we should always put the test result in the context of the other information we have. It’s a lesson that endures throughout medicine: Look at the big picture, not a single piece of data. Triangulate on the truth, using all the sources of information you have, no matter how good a single test. And don’t be shy about questioning a conclusion that doesn’t fully fit the facts.
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