Antigen, Antibody or PCR tests: What is the difference?

Antigen testing, antibody testing, PCR (Polymerase Chain Reaction) tests. . . what’s the difference? Which one is the most reliable? Which is right for my situation?

As the number of COVID-19 cases climb, the need to test more people increases. Even with the hope offered by vaccines, there is no doubt that coronavirus testing is still required and remains a critical part of controlling the spread of this global pandemic. The reason for this is simple – accurate and reliable testing is a proven and effective way to slow the spread of SARS-CoV-2, the virus that causes COVID-19.  Slowing the spread of this deadly virus will save lives, reduce burden on our health care systems and keep our workforce safe. There has been a lot of discussion in the news about the types of tests currently on the market and when you factor in the ones that are in development it can be hard to decide which testing approach is the right fit for given situation.  

Antigen, antibody, and PCR testing all have their pros and cons.  It is important to distinguish that these tests don’t all look for the same things. As new tests come to market, in particular antigen and antibody tests, it is important to understand these differences and learn which test is right for which situation.

For any approved COVID-19 test currently on the market, be it antigen, antibody or PCR based, there should not be any reliability concerns, if these tests are conducted properly, by the appropriate personnel, and using the appropriate space, equipment, and reagents to conduct the test.  The real question should be about which type of testing to use for specific information regarding the COVID-19 situation. Let’s compare the three testing methodologies paying attention to things like what the test detects, how and where the test is typically performed and most importantly what kind of information the test provides and in what situation is it most helpful.

PCR tests are currently the most commonly used type of test to detect whether a person has an active COVID-19 infection.  These tests look for genetic material from the SARS-CoV-2 virus that causes COVID-19.  Once a sample is collected by a health care professional, these tests can be done quickly (1-2 hours) at the place of testing or can be done in a large central lab (anywhere from a few hours to a few days).  These test are the gold standard and can be used to diagnose a COVID-19 infection without any additional confirmatory tests. They often require specialized equipment to run the test (ex. a thermocycler) and with the right set up can be used in a remote setting.

Antigen tests, often referred to as “rapid tests” are also used to detect if a person is currently infected, but tend to perform better if a person has had symptoms for a few days. These tests are designed to detect pieces of the proteins that make up the virus.  Once a sample is collected by a health care provider, antigen tests can often be done quickly while you wait (a few minutes to about an hour or so), but occasionally they are sent to a central lab.  One thing to keep in mind is that for the current antigen tests on the market, an additional PCR test is required to confirm an antigen test result. Since antigen tests typically don’t require a lot of special equipment, they can be well suited to remote settings.

Lastly, antibody tests (also called serology tests, but not to be confused with antigen tests) look for COVID-19 antibodies in the blood and are the least commonly used testing method for population wide COVID-19 testing.  Antibodies are molecules made by the immune system in response to SARS-Cov-2 and so a positive antibody test can indicate that the person was exposed to or infected by the virus in the past. Because antibody tests require a blood draw, samples are almost exclusively taken by a health care professional and sent to a lab for testing.  While antibody tests are not best suited to determine if a person is currently infectious, understanding who has been exposed to the virus in the past can be helpful. 

The following table, adapted from the DC Health publication, summarizes and expands upon the differences between these three types of testing approaches.

TOPICPCR TESTANTIGEN TESTANTIBODY (SEROLOGY) TEST
WHAT IS THE TEST LOOKING FOR?PCR tests look for pieces of genetic material from SARS-CoV-2, using samples from the nose, throat, or other areas in the respiratory tract.Antigen tests look for pieces of proteins that make up the SARS-CoV-2 virus, using samples from the nose, throat, or other areas in the respiratory tract.Serology tests look for antibodies1; molecules made by the immune response against SARS-CoV-2 in the bloodstream.
WHAT DOES THE TEST TELL YOU?Determines if the person has an active (i.e., current) infection.Determines if the person has an active (i.e., current) infection.Determines if there was a past infection.
HOW IS THE TEST PERFORMED ON PEOPLE?In most cases, a nasopharyngeal or nasal swab is taken by a healthcare provider and tested; however, oral swabs and saliva are also acceptable. Sometimes the test can be run while you wait, but most commonly, the swab needs to be sent to a lab for testing.In most cases, a nasopharyngeal or nasal swab is taken by a healthcare provider and tested. Most often the test can be run while you wait, and occasionally the swab needs to be sent to a lab for testing.In most cases, a blood sample is taken by a healthcare provider and is sent to a lab for testing.
WHEN IS IT HELPFUL?It can help determine who has an active infection, regardless of a person’s symptoms.
• It can help identify people who are contagious to others.
• In communities where transmission rates are low and mitigation efforts are effective, PCR testing is more reliable at detecting active infection.
• It accurately identifies people who are or are not infected with SARS-CoV-2.
For someone with symptoms, it can be used as a point-of-care test to quickly determine who has an active infection.
• It can help identify people who are contagious to others.
• It is a less expensive test than PCR.
• It performs best 5-7 days after symptoms onset, in the early stages of infection with SARS-CoV-2.
It can identify people who had an infection in the past, even if they had no symptoms of the illness.
• In some cases, it could help determine when COVID-19 occurred since we know that IgM forms before IgG and that IgM goes away before IgG.
• It can help determine who qualifies to donate convalescent plasma (a blood product that contains antibodies against COVID-19 and can be used as a COVID-19 treatment).
• If many people take the test in a community, it can help public health leaders and researchers know what percentage of the population already had COVID-19.
LIMITATIONSIt does not help determine who had an infection in the past.
• It also gives you a result for the point and time when the specimen was collected and cannot predict if you will remain negative. For example, if you are quarantining after an exposure, a negative test does not allow you to stop quarantining.
• In some people, the virus can be found by PCR in the nose and throat for several weeks, even longer than their infectious period (the time they are contagious to other people).
• This test requires certain kinds of swabs and reagents that may be in short supply.
Best results are achieved with those who are symptomatic, and it will not help determine who had an infection in the past.
• Antigen tests have lower sensitivity3 than PCR tests, so there may be false-negative results.
• In persons with symptoms or known exposure, negative tests must be treated as a preliminary result and confirmed with PCR testing.
If used too close to the beginning of an infection, this may result in a negative test which is why it must not be used to detect active COVID-19 infection.
• In areas where there have not been many cases of COVID-19, many of the positive test results will be false positives (see Positive Predictive Value2). Some antibody tests have low sensitivity3 and specificity4 and thus may not produce reliable results.
• Some antibody tests may cross-react with other coronaviruses that are not SARS-CoV-2, leading to false test results.
• We do not know yet if having antibodies to the virus that causes COVID-19 can protect someone from getting infected again or, if they do, how long this protection might last. Until scientists get more information about whether antibodies protect against reinfection with this virus, everyone must continue to take steps to protect themselves and others. This includes staying at least 2 meters away from other people (social distancing), even if they have had a positive antibody test.
WHAT DOES A POSITIVE TEST RESULT MEAN?A positive PCR test means that the person tested has an active COVID-19 infection.A positive antigen test means that the person tested has an active COVID-19 infection.A positive antibody test means that the person tested was infected with COVID-19 in the past and that their immune system developed antibodies to try to fight it off. Until scientists get more information about whether antibodies protect against reinfection with this virus, everyone must continue to take steps to protect themselves and others. This includes staying at least 2 meters away from other people (social distancing), even if they have had a positive antibody test.
WHAT DOES A NEGATIVE TEST RESULT MEAN?A negative PCR test means that person was probably not infected at the time their sample was collected.
It doesn’t mean that someone won’t get sick – it only means that they didn’t have COVID-19 at the time of testing.
A negative antigen test means that SARS-CoV-2 viral proteins were not detected.
In persons with symptoms or known exposure, a negative test does not rule out COVID-19. The individual must quarantine until a confirmatory PCR test can be completed.
A negative antibody test means that the person may not have had COVID-19 in the past. However, they could still have a current infection, and the antibody test was conducted too soon to give a positive result.

1 The body forms antibodies to fight off infections. Immunoglobulin M (IgM) is the first antibody formed against a germ, so it appears on tests first, usually within 1-2 weeks. The body then forms immunoglobulin G (IgG), which appears on tests about two weeks after the illness starts. IgM usually disappears from the blood within a few months, but IgG can last for years. Some antibody tests test for IgM and IgG, and some only test for IgG.

2 Positive predictive value is a measure of how likely it is that a positive test is a true positive rather than a false positive. This is dependent on how many people in the population have tested to have had the disease. When there are very few people in the population that have had the disease, then there is a higher chance for a false positive. When many people in a population have had the disease, then there is a higher chance that a positive test is a true positive.

3 Sensitivity is sometimes called the “true positive rate.” It measures how frequently the test is positive when the person tested has the disease. For example, when a test has 80% sensitivity, the test detects 80% of patients with the disease (true positives). However, 20% of patients with the disease are not detected (false negatives) by the test.

4 Specificity is sometimes called the “true negative rate.” It measures how frequently the test is negative when the person tested doesn’t have the disease. For example, when a test has 80% specificity, the test correctly reports 80% of patients without the disease as negative (true negatives). However, 20% of patients without the disease are incorrectly identified as testing positive (false positives) by the test.

It’s important to remember that no test is 100% accurate all the time. Some things that may affect the test’s accuracy include:

  • You may have the virus, but the swab might not collect it from your nose or throat.
  • The swab or mucus sample may have been accidentally contaminated with the virus during collection or analysis.
  • The nasal or throat swab may not have been stored at the correct temperature before it was analyzed.
  • The chemicals used to extract the virus genetic material and make copies of the virus DNA may not work correctly.

COVID-19 Testing at Various Infection Stages

It’s clear that each testing approach has its pros and cons, and there is a place for all three in the global effort to control the spread of COVID-19. As per the chart COVID-19 Testing at Various Infection Stages, it is clear that every day of infection counts, and that tests with higher sensitivity allow for earlier detection of the virus, and we can see what technology can be used to detect the virus at earlier stages. When it comes to screening people for infection, PCR testing remains the most common type of test used in Canada and the USA.  According to Dr. Christina Wojewoda, a pathologist at the University of Vermont and the vice-chair of the College of American Pathologists’ microbiology committee, we “should be diagnosing people with PCR tests because they are the most accurate”. Our SARS-CoV-2 real-time RT-PCR test kit can bring PCR testing to workplaces, community settings, and pop-up service centres, even in the most remote communities.  Our approach provides a safe, easy, and accurate way of testing to ensure a safe workplace.

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