Understanding COVID-19 Testing

This week, we had a very interesting discussion at work about COVID-19 testing, prompted by a tweet from Elon Musk. Even in a group of people I consider brilliant, it was clear we were (including me) a little confused about COVID tests. So I decided to do a little research to answer some questions I had and post the answers with a little bit of context of science and statistics.

The bottom line is: in many cases, COVID-19 testing is a clue, not an answer. It can tell you if you definitely have, most likely have, probably have, probably do not have, most likely do not have COVID-19. Testing cannot tell you that you definitely do not have COVID-19.

Tests are helpful, but are only a piece of the puzzle. The most important things you can do to protect your health and others are to:

  • If you are well: Wear a mask AND keep >6 feet of distance from those you don’t live with. If you are outside, you should still wear a mask unless your exposure to others is brief and distant.
  • If you or someone in your household is sick: the sick person should separate completely from anyone else, including those in the house (self-isolate), and the rest of the household should stay home (quarantine).

The CDC has a Self Checker to help you make testing decisions, and the FDA has a helpful video.

What is the difference between the types of tests?

Types of tests for COVID-19: swabs indicate tests done by swab up the nose or through the mouth, the syringe indicates a blood test by finger stick or through the arm
Test typePCR test
Other namessometimes called nucleic acid test, qPCR, RT-PCR, molecular test, genetic test, diagnostic test, viral test, nucleic acid amplification test (NAAT), LAMP test
What if I get a positive result?If you get a positive result, you have COVID-19. This test is the “gold standard” – PCR is a sensitive test that is very specific for COVID-19. Testing positive for COVID-19 without being infected is theoretically possible due to a lab mistake, but unlikely.
You should self-isolate and people who live with you should quarantine for as long as your health care provider or health department recommends.
What if I get a negative result?There is still a chance you have COVID-19. This test can only find COVID-19 if the swab picks up enough virus to test. You could have growing amounts of virus that the swab did not pick up.
You should talk to your health care provider about your symptoms and possible exposure to COVID-19 to find out if you should be retested at a later date and if you should self-isolate or quarantine.
Test typeAntigen test
Other namessometimes called rapid test, viral test, diagnostic test
What if I get a positive result?If you get a positive result, you may have COVID-19. The likelihood of you having COVID-19 depends on how many people in your community have the virus (see below for explanation) and your exposure.
You should self-isolate and your household should quarantine, but you may need to follow-up. Talk to your health care provider about your symptoms and possible exposure to COVID-19 to find out if you should have a PCR test.
What if I get a negative result?There is still a chance you have COVID-19. This test can only find COVID-19 if the swab picks up enough virus to test. You could have growing amounts of virus that the swab did not pick up.
You should talk to your health care provider about your symptoms and possible exposure to COVID-19 to find out if you should have a PCR test and if you should self-isolate or quarantine.
Test typeAntibody test
*This test does not test for COVID-19 infection. This test is best used for research purposes, or to find out if your current health problems could be due to a recent COVID-19 infection where the virus is no longer able to be found by other tests.*
Other namesSerological test, serology, blood test, serology test
What if I get a positive result?You have antibodies that are similar to the ones made to fight COVID-19. You may currently have a COVID-19 infection or may have had one in the recent past. You could also have been infected with a virus that was similar to COVID-19.
You should get a COVID-19 PCR or antigen test to find out if you still have an active infection.
If you do not have an active infection, a positive antibody test may not mean you are immune to COVID-19. You should continue to take precautions to avoid spreading COVID-19.
Consider donating plasma to help others.
What if I get a negative result?This does not mean you do not have COVID-19. This test does not test for the presence of the virus, and your body may not have made antibodies to the virus yet. If you need to test for COVID-19, you need a PCR or antigen test.
You may not have ever had COVID-19. If you never had exposure or symptoms, this is the most likely answer.
You may have had a COVID-19 infection in the past. Antibody levels can drop over time, so you could have had an infection but no longer have antibodies.

Why can’t the tests tell me that I definitely don’t have COVID-19?

There is a curve of infection that happens after you are exposed to COVID-19. The virus is in your body and multiplying. Once the virus gets high enough, sensitive PCR tests find the genetic material inside the virus shell and less sensitive antigen tests find pieces of the virus shell. As you recover from the virus, antibodies appear and the virus level decreases. Over time, the antibodies also disappear.

https://www.bd.com/en-us/offerings/capabilities/microbiology-solutions/point-of-care-testing/bd-veritor-plus-system-for-rapid-covid-19-sars-cov-2-testing

All tests have limits for how little of the virus they can find, called the limit of detection. Depending on when you are tested, your level of virus may be too low for the test to find. If you were tested earlier or later, you may get a different result because your levels of virus got higher or lower. At first, you could test negative because there is not yet enough virus at the spot they swab to test above the limit of detection. The date you were exposed and what symptoms you are experiencing are important clues to where you are on the curve.

In the early days of infection, your virus level could be negative because it is below the limit of detection of the test.

If your levels of virus are in a zone where the test is not accurate, you could get inconclusive results, which is likely what happened in Elon Musk‘s case.

This is the reason why if you have been in close contact with a COVID-19 case, the CDC still recommends you self-isolate for 14 days even if you have a negative test and do not have symptoms.

Why does the amount of positive cases in my community affect how I interpret my antigen test?

Antigen tests are an important tool in our battle against COVID-19, but due to the way the tests work, there is a possibility of testing positive when you do not have the virus (false positive) and testing negative when you do have the virus (false negative).

Due to an interesting quirk of statistics, your chance of getting a false positive increases when the chance of you catching COVID-19 is low. Your chance of a false positive decreases when the chance of you catching COVID-19 is high. How is this possible? The opposite is true for false negatives – when your chance of catching COVID-19 is high, you are more likely to get a false negative.

BD, who manufactures the Veritor Plus System for rapid COVID-19 (SARS-CoV-2) testing, has a nice graphic of this phenomenon on their webpage. They state here that their test has a specificity of 99.5%, which means 1 out 200 tests will be a false positive. They also state that their test has a sensitivity of 84%, which means if we used the test on 200 people who are all later confirmed to have COVID-19, 168 will test true positive, and 32 will have false negatives.

Positive predictive value is the chance that your positive is a true positive. Prevalence means how many people in your community have an active case of COVID-19. As you can see, when there are very few COVID-19 cases in your area, your chance of your positive result being correct could be as low as 9.1%! However, if your chance of COVID-19 infection is higher (due to high community spread or known exposure), your chance of your positive result being correct is >90%.

https://www.bd.com/en-us/offerings/capabilities/microbiology-solutions/point-of-care-testing/bd-veritor-plus-system-for-rapid-covid-19-sars-cov-2-testing

This seems to make no logical sense. The way the test works should not change based on what is going on in the outside world, right?

Let’s imagine we mail this antigen test to a secluded island nation that has never been exposed to COVID-19. The test is accurate 99.5% of the time, which means for every 200 tests performed, 1 will be a false positive. So, residents of this island who test positive have a 100% chance that it is a false positive. There are no false negatives or true positives in this case because COVID-19 does not exist on the island.

Now, let’s look at the state of NC (DHHS testing dashboard). Of the people who are getting tested for COVID-19, 7.9% are testing positive by PCR tests. (People getting tested are more likely to have COVID-19 than NC residents as a whole, because people getting tested are more likely to have had exposure or symptoms.) If we were to take 200 of those people in NC who had a PCR test in the last few days, 16 of them would have COVID-19. If we tested all 200 with the BD antigen test, 14 people would test positive. Of those, 1 would still be false positive from the test as we saw above. Because this test catches 84% of positives, 3 of the positive people will test false negative and the remaining 13 will test true positive. For those who tested positive, their chance of having COVID-19 is 93%. Their chance of a false positive is 7%. For those who tested negative, their chance of having COVID is 2%.

Now, let’s look at a hypothetical case where a workplace in Sampson County, NC wanted to test all 200 of their employees with the rapid antigen test, even though there had not been any known exposure. According to NC DHHS, there have been 538 cases per 100,000 residents in the last 14 days, which is about 1 person out of 200 people. We would still have our 1 false positive from the test, and 1 true positive. So of the 2 people who receive positive results, they each have a 50% chance of having a false positive.

On average, the chance of a false negative is slim – but if just 1 person tested false negative due to being at an early but still contagious stage of infection, having a party based on these results could get several people sick.

Now let’s imagine a super spreader event. There was a large indoor wedding where people sang together, laughed, and yelled to hear each over the music for hours. They hugged and shook hands while enjoying appetizers. Of the 200 people who attended, 130 people were later confirmed COVID-19 positive by the PCR test. If we tested all 200 attendees with the BD antigen test, 110 people would test positive. Of those, 1 would still be false positive from the test as we saw above. Because this test catches 84% of positives, 21 of the positive people will test false negative and the remaining 109 will test true positive. For those who tested positive, their chance of having COVID-19 is 99%. Their chance of a false positive is 1%. For those who tested negative, their chance of having COVID is 23%.

In each case, the 1 false positive out of 200 tests stays the same – but the number of total COVID-19 positive cases changes, which causes the chance of a positive actually being a false positive to change.

After seeing these examples, it’s easier to understand why the antigen test is recommended for people with exposure or symptoms of COVID-19 and not for general screening, and also why preventative isolation and a follow-up PCR test is important in cases where the risk of a false negative is high. Results from general screening may be useful to determine trends, and may catch some true positive cases, but it also may give a sense of false security because it does not catch early cases (as in the now famous event at the White House Rose Garden) and may sideline false-positive people who are not sick.

An important note on false negatives – unlike false positives, they are due to a combination of factors related to where you are in your COVID-19 course of infection and factors related to the test itself. Although BD reports an average false negative rate – your personal risk of a false negative rate may be higher or lower depending on your personal circumstances. Also, although the PCR test is much less likely to have false positives, false negatives like the example above can happen with the PCR test as well.

Does this mean that the number of positive tests reported in the media is wrong?

Each state has their own method of testing and reporting results. These results will always be an estimate because not everyone gets tested. In states that report antigen results, there is a possibility that false positives will get reported. The best state health departments can do is set clear rules for testing and reporting results and look at trends over time. In NC, DHHS reports antigen results separately. Right now they are <5% of the total.

If you have doubt that the increase in the cases is real, you can also look at hospitalization and death trends.

How should I interpret my test results?

  • Be informed and ask your health care provider to help you interpret the results based on your personal situation.
  • Err on the side of caution. If you have symptoms or confirmed exposure, follow CDC guidelines on how to keep others safe.
  • Do not use negative test results to have a maskless gathering. It’s safer to quarantine 14 days before getting together, keep masks on, or have a virtual visit.
  • Do not use a previous positive PCR, antigen, or antibody test result to act “immune.”

Where can I learn more?

CDC information on testing (for the public)

CDC information on testing (more detailed for health care workers)

FDA information on testing

Khan academy statistics explanation