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Can we trust antibody tests to tell who has been infected and who hasn't?

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Antibody tests are now available in many parts of the world, and they can play an important role in understanding COVID-19 trends and identifying groups at higher risk for infection.  Diagnostic tests are never 100% accurate. Sometimes, a test will produce false positives (when you test positive for the virus, but don't have it) and false negatives (when you test negative for the virus, but you really have been infected). The antibody tests for COVID-19 are similar. To be able to trust the results of an antibody test, we must look at its ability to detect the presence of COVID-19 antibodies when they are present, and its ability to confirm the absence COVID-19 antibodies when they are truly absent.  In the context of the current pandemic, it is important for us to reduce the amount of false positive test results that can occur by choosing a test that is highly specific. This means we must choose a test whose ability to correctly identify those without the disease is as accurate as possible, so that a negative test result truly means that person has not been infected with COVID-19. This is because an individual with a false positive test result may be mistakenly reassured that they are safe, and may pay less attention to basic prevention (e.g., social distancing). In this context, the U.S. CDC recommends choosing a test with very high specificity, perhaps 99.5% or greater. Irrespective of where people reside, they should choose the test available on the market with the highest specificity. However, it is important to note that at this stage of the pandemic, we don't know yet exactly what a positive antibody test means in practice. We are not sure yet if a positive antibody test means that the antibodies will give the person immunity (i.e. prevent them from getting sick again with COVID-19); and if they do, how long this protection can last (weeks? months?). Several studies are currently underway.

This article was published on
August 14, 2020

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What our experts say

Antibody tests are now available in many parts of the world, and they can play an important role in understanding COVID-19 trends and identifying groups at higher risk for infection.  Diagnostic tests are never 100% accurate. Sometimes, a test will produce false positives (when you test positive for the virus, but don't have it) and false negatives (when you test negative for the virus, but you really have been infected). The antibody tests for COVID-19 are similar. To be able to trust the results of an antibody test, we must look at its ability to detect the presence of COVID-19 antibodies when they are present, and its ability to confirm the absence COVID-19 antibodies when they are truly absent.  In the context of the current pandemic, it is important for us to reduce the amount of false positive test results that can occur by choosing a test that is highly specific. This means we must choose a test whose ability to correctly identify those without the disease is as accurate as possible, so that a negative test result truly means that person has not been infected with COVID-19. This is because an individual with a false positive test result may be mistakenly reassured that they are safe, and may pay less attention to basic prevention (e.g., social distancing). In this context, the U.S. CDC recommends choosing a test with very high specificity, perhaps 99.5% or greater. Irrespective of where people reside, they should choose the test available on the market with the highest specificity. However, it is important to note that at this stage of the pandemic, we don't know yet exactly what a positive antibody test means in practice. We are not sure yet if a positive antibody test means that the antibodies will give the person immunity (i.e. prevent them from getting sick again with COVID-19); and if they do, how long this protection can last (weeks? months?). Several studies are currently underway.

Context and background

While COVID-19 diagnostic tests determine whether or not a person is currently infected with the virus, antibody tests are used to determine whether or not a person was infected with COVID-19 in the past. This occurs through a process in the immune system whereby the body develops a type of protein called 'antibodies' in response to the presence of a foreign object threatening the body, also called an "antigen", which in this case is the virus. The antibodies latch onto antigens and then work to remove them from the body. Antibodies are detected in the blood of people who are tested after infection; they show the body’s efforts to fight off a specific infection. This is why antibody tests can determine whether or not a person has had a specific virus.

In comparison, tests for active cases of the virus (such as a polymerase chain reaction (PCR) test) looks for the actual genes of the virus itself in a person. This means that COVID-19 has to be active and have a large enough amount infecting in a person in order for the test to be accurate. One difference between these tests is the fact that antibody tests look for prior infection from a virus using blood, whereas PCR-based tests are run on saliva or mucus samples to look for the virus's genetic material and diagnose people who are currently infected with the novel coronavirus.

Each tests have different levels of of specificity (how well a test identifies patients who do not have a disease) and sensitivity (how well a test identifies patients who do have a disease), and each have different ideal standards.

For instance, while with antibody tests the key metric is specificity, with diagnostic tests, the key metric is sensitivity. This is because an individual with a false negative test result may be mistakenly reassured that they are safe (just as one would with a false positive antibody test), and in turn pay less attention to basic prevention (e.g., social distancing).

Resources

  1. Interim Guidelines for COVID-19 Antibody Testing (U.S. CDC)
  2. Waiting for Certainty on Covid-19 Antibody Tests - At What Cost? (NEJM)

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