I tested negative. Am I safe?

More folks than ever are getting tested for SARS-CoV-2, the virus that causes COVID-19. Access to testing is great, and long overdue.

But the tests themselves remain problematically inaccurate, so remember that a negative test doesn’t necessarily put you in the clear.

The issue is false negatives: tests that don’t detect the virus when a person is actually infected. And these tests we’re using to determine viral presence is prone to false negatives.

This matters because people who test negative may take fewer precautions to protect those around them — even though they may actually be infectious.

If you’re sick, pay attention to your experience rather than your test results — and act accordingly. But if you’re not sick, don’t take the test’s word for it.

How bad is the problem? Researchers at Johns Hopkins School of Public Health scoured the existing scientific literature — both published, peer-reviewed studies and those that are still going through the process — to answer that question. They looked at data for the RT-PCR test, generally a very sensitive way to detect viruses, that is the primary swab-up-the-nose test used to detect active infection.

The short version: At best, one in five tests will have false negatives.

Published in the May 13, 2020 edition of Annals of Internal Medicine, the study found a sweet spot in the progression of infection. Testing on Day 8 of the infection — usually the third day of disease symptoms — is when you’re most likely to get the most reliable results.

Here’s how it breaks down:

  • Day 1 of infection (often no symptoms): 100-percent chance of a false-negative test.
  • Day 4 of infection (often no symptoms): 67-percent chance of a false-negative test.
  • Day 5 of infection/symptom onset: 38-percent chance of a false-negative test.
  • Day 8 (three days after symptom onset): 20-percent chance of a false-negative test.
  • Day 9 (4 days after symptom onset): 21-percent chance of a false-negative test.
  • Day 21: 66-percent chance of false-negative test.

These numbers represent median observations: in half the cases the chances were higher, in half they were lower. This is the middle ground of numbers that have a pretty large spread, especially when testing the early days of infection.

Going with these median numbers, you’ll see that even at the Day 8 sweet spot, one in five tests will falsely report a negative result when the person is actually positive. So at best there’s a 20% false negative rate. On other days, the false negative rate is even higher.

Why are the false negatives so high on a test that is known to be exquisitely sensitive? A physician colleague of mine working in a front-line lab suggests that incorrect or incomplete collection may be the problem. The swabs healthcare workers stick up patients’ noses may just not be catching enough viral particles. I’ve got a message out to a microbiologist friend for his take, and will update this post when I hear back.

I get that people want to know what’s going on. I want to know what’s going on. These acute tests (the swab-up-the-nose tests) more usefully inform our actions when they’re positive than when they’re negative.

If you get a positive test, talk to your doctor about appropriate medical care, stay home, stay away from people, and do everything you can to take care of yourself.

If you get a negative test, don’t assume you aren’t sick or that you can’t infect others. If you aren’t on your third day of symptoms (and even if you are), there’s a good chance the test won’t catch your infection.

Be careful, folks. And remember that getting a negative test isn’t the final word.

Salúd!

—Dr. Orna

P.S. Read the full Annals of Internal Medicine article, “Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure.” Here are the key findings if you don’t want to wade through it:

“Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset) then began to increase again, from 21% (CI, 13% to 31%) on day 9 to 66% (CI, 54% to 77%) on day 21.”

Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure.Annals of Internal Medicine, 13 May 2020.

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