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7:54 a.m. - 2020-08-10
Several different tests are used to detect SARS-COV-2, the virus that causes Covid-19 infection, and it's not always clear in news reports which test is being used or what it identifies.

Two general types of test are used to diagnose Covid-19. Both of them begin with a nasopharyngeal swab. MOLECULAR tests look for RNA, the genetic material of the virus, using a multiplying technique called PCR (polymerase chain reaction) to make the RNA easier to measure. Molecular testing takes longer than other types of tests but is highly accurate. The second diagnostic test, ANTIGEN tests, looks for proteins that are unique to the SARS-COV-2 virus. Antigen tests are faster and less expensive than molecular tests but more prone to error. Both molecular and antigen tests are used to find current or active infections.

Another category of tests, ANTIBODY testing, requires a blood sample, so it might begin with a finger stick or venipuncture. Antibody tests are sometimes referred to as "serology testing." They are not used to diagnose a current infection, but rather to detect antibodies that the patient has manufactured while fighting Covid-19. Thus, antibody tests indicate a recent infection, not an active one.

When the Covid pandemic first began, the virus which causes it was new to human experience, so there were not tests for it. The FDA issued emergency use authorizations (EUA) for different tests in order to correct that situation and make testing possible. Molecular tests have to be 95% sensitive and 100% specific in order to get an EUA. Antigen tests have to be only 80% sensitive, while antibody tests must be 90% sensitive and 95% specific.

SENSITIVITY means that you can trust a negative result to be true; a highly sensitive test will not miss the molecules that it is testing for. In other words, there will be very few "false negatives." If a test is 90% sensitive, then on average, only one in ten tests will show a false negative. The mnemonic SnNOut is used to summarize that "a Sensitive test that comes up Negative rules Out an infection."

SPECIFICITY. means that you can trust a positive result. The test doesn't mistake other molecules for what it's supposed to be measuring, so there will be few false positives. A test that is 90% specific means that only one in ten results, on average, will show false positives. Here the mnemonic SpPIn means " a Specific test that comes up Positive rules In the infection."

So, for example, any test that is 100% specific but only 80% sensitive, would have no false positives but potentially 20% false negatives.

A negative antigen test in a symptomatic patient should therefore be verified with a followup molecular test. An antibody test given early in the infection could give a false negative if the antibodies haven't had time to form as part of the immune response. A positive antibody test means that the patient had a Covid infection in the past, but does not indicate current infection. Ideally, it could mean that the patient could donate blood rich in antibodies to help treat other people with a current and serious infection. Unfortunately, at this stage of the game, we don't know if a positive antibody test guarantees immunity to future infections or, if so, for how long. Either molecular or antigen tests could produce a false negative if the nasopharyngeal swab was done incorrectly or if the sample was handled incorrectly on the way to the laboratory.

Molecular tests and antibody tests therefore measure different things. One measures active infections, the other recovery from a past infection. Reporting them together in one statistic is like combining apples and oranges. An infected person given an antibody test could produce a false negative because the test was given early in the infection, thus giving a false sense of security. Since none of the tests currently available are 100% sensitive, false negatives are always a possibility, though less so with molecular tests.


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