From the WebMD Archives

May 14, 2020 -- With a pandemic moving as fast as COVID-19, so does the science working to contain it. New tests come to the market quickly, and some are more reliable than others. We consulted experts to bring you answers to common questions.

Q: I’ve heard of diagnostic or PCR tests, antibody tests, and now antigen tests. What’s the difference?

A: Testing for COVID-19 falls into two categories:

  • Diagnostic tests look for the live virus, either on a molecular level (known as PCR tests) or by looking for viral proteins that are part of the virus itself (known as antigen tests).
  • Antibody tests, also known as serological tests, use your blood to detect antibodies produced by your immune response to the virus -- not the virus itself. Because antibodies generally can’t be detected until after you’ve had the virus for a while, this kind of test can’t be used for diagnosis. It’s more helpful for scientists who are tracking the spread of the disease, or preparing for eventual vaccine trials.

Q: How does each one work?

A: Diagnostic tests start from the same place -- a specimen collected via swab -- but after that, they take separate paths. And antibody tests work in a completely different way.

  • PCR tests use a sample of mucus taken from your nose or throat. That’s gathered by inserting a long swab through your nostril or mouth to the back of your throat, which gets rotated or rubbed against the surface to absorb the secretions. Those secretions are subjected to a technology called polymerase chain reaction (PCR), which duplicates the virus’s DNA numerous times, if it’s there, until it’s detectable.

Most of the time, these tests are run in a lab, which produces accurate results in 1 to 2 days. Some are done on-site, and you’ll get the results in minutes. But no test is perfect, and some rapid-result tests yield a larger number of false negatives.

  • Antigen tests are a new development for diagnosis -- the FDA just issued the first emergency use authorization on May 9. These kinds of authorizations mean a particular product fills an unmet need in an emergency, but it has not been reviewed and approved by the FDA. These tests, too, use a swab to collect a specimen, but instead of needing to replicate DNA, antigen tests can quickly spot fragments of proteins from the virus.

You can get results while you wait, and positive results are highly reliable. But because of the different way they work, they miss more active infections than PCR tests.

“It has the potential for being as good as a pregnancy test for making a rapid diagnosis at the point of care, and it’s cheap,” says Joseph Vinetz, MD, a professor of infectious diseases at Yale University. But we’re not there yet.

  • Antibody tests use a blood sample to see if your body’s immune system has produced antibodies, which show if you’ve been exposed to the virus, not whether you have an active infection. And even though it’s looking for an immune response, a positive antibody test doesn’t mean you’re immune to the virus. Because COVID-19 is so new, we simply don’t know yet if you can be infected again.

Q: Which test do I need, and how do I get it?

A: On-demand diagnostic testing still isn’t available in many places. Because the tests are in short supply, the CDC has set up guidelines for who should be tested. Those include anybody with symptoms as well as people without symptoms who get priority from health departments or health care providers for some reason. So the first step would be to talk to your doctor to see if you qualify. They’ll tell you what to do next.

If you suspect you may have had the virus and want confirmation, talk to your provider about getting an antibody test.

Q: How big a deal are false negatives?

A: False negatives can happen because some tests are more reliable than others, or because of the way the specimen was gathered. For example, getting a swab thrust into the back of your throat can be an unpleasant experience, and if you have trouble tolerating it, the sample might not capture enough material. Or the virus might have already migrated from your throat down into your lungs, where a swab won’t reach, says Vinetz.

“No test is 100% accurate,” says Gary Procop, MD. He leads COVID-19 testing at Cleveland Clinic. He used samples known to be positive for the coronavirus and compared the results of five different tests. The study, which hasn’t been published yet, found that accuracy varied widely. One rapid-response molecular test provided false negatives for almost 15% of the specimens. But in terms of real-world effects in an outpatient setting, Procop says that if the provider is explaining things properly, those false negatives probably won’t cause harm.

“Say Mrs. Jones comes in with possible COVID. If the rapid test is falsely negative, the provider will still tell her that no test is 100% accurate, and she should still go home and self-isolate, wear masks, and so on,” he says. “The guidance hasn’t changed, and you haven’t put other people at risk.”

The protocol for rapid-response tests usually includes a confirmation test in a lab, which should discover the true positive. Procop warns that less accurate tests shouldn’t be used in a hospital setting, for instance when doctors are deciding whether to admit a patient to a COVID-19-free ward.

False negatives become dangerous if a patient disregards the provider’s advice and acts as if the test result means they’re free and clear.

Q: How can I tell if the test I received is reliable?

A: Ask your provider. If they don’t know the specifics of the test they’re giving you, they can contact the lab they’re using to get the information. “Folks in the lab are always happy to provide details on the kind of test, the performance characteristics, and so on,” says Procop.

Q: Can I take an at-home test?

A: The idea of getting tested without leaving the safety of your own home is appealing for several reasons. “A big goal of the public health response is about expanding testing. At-home testing helps us reach asymptomatic people, or people with mild symptoms who could spread the virus if they go out,” says Denis Nash, PhD, executive director of the City University of New York Institute for Implementation Science in Population Health.

The FDA hasn’t approved any tests that can be done fully at home yet -- you can’t collect your own specimen and get results. But it has given emergency use authorization to several test kits that have you collect a specimen and send it to a lab for processing. Any test that doesn’t appear on an FDA list hasn’t been authorized, so you shouldn’t trust it.

Q: My antibody test came back positive, and I feel fine. Can I go back to work now?

A. Sorry, no. “People want it to be a passport to COVID freedom, a get-out-of-jail-free card, but we don’t know that yet,” says Vinetz. “We don’t know if antibodies are protective against infection, or if it means you’re not infectious.”

So for your own safety and the safety of the outside world, stay home.

Q: What will my insurance cover?

A: Unfortunately, there’s no easy answer here. You may have seen news reports that the Trump administration has directed private health insurance companies to cover 100% of the costs for COVID-19 testing, but the reality is muddy -- people have received bills for thousands of dollars related to getting a diagnosis. Because everything is happening so quickly, insurance companies are changing their policies on the fly, and the details can take a while to trickle down from the CEO’s office to the claims processor, says Sue Null of medical bill advocacy firm Systemedic Inc.

“We’re calling the insurance companies every time a bill shows cost sharing, and I’d say 80 to 90% of the time, it’s been processed incorrectly,” she says.

Before you go in for a test, Null advises, call your insurance company. They may cover only a certain test, or from a particular lab or hospital. Get those details, and be sure to write down the representative’s name, the reference number you receive, and the date and time. And make sure the call is being recorded. That way, if you do get a bill, you can go back to the insurer with your records. “They’re bound by what the representative said,” Null says. “They’ll have to make good on it.”

Show Sources

CDC: “Testing for COVID-19,” “Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-19),” “Frequently Asked Questions,” “Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19),” “Test for Past Infection.”

FDA: “Coronavirus (COVID-19) Update: FDA Authorizes First Antigen Test to Help in the Rapid Detection of the Virus that Causes COVID-19 in Patients.”

Joseph Vinetz, MD, professor, Section of Infectious Diseases, Yale University.

Gary Procop, MD, medical director and co-chair, Enterprise Laboratory Stewardship Committee, and director of molecular microbiology, virology, mycology, and parasitology, Cleveland Clinic.

NPR: “Study Raises Questions About False Negatives From Quick COVID-19 Test.”

Denis Nash, PhD, executive director, City University of New York Institute for Implementation Science in Population Health, and distinguished professor of epidemiology, CUNY School of Public Health.

Centers for Medicare and Medicaid Services: “Trump Administration Announces Expanded Coverage for Essential Diagnostic Services Amid COVID-19 Public Health Emergency.”

NBC News: “Got coronavirus? You may get a surprise medical bill, too.”

Susan Null, Systemedic Inc.

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