A Primer on COVID-19 Testing Methods
There are three types of diagnostic tests : PCR, antibody, and antigen testing. PCR and antigen testing are actually testing for the presence of parts of the virus. Antibody testing is measuring the body’s immune response to the virus and two types of antibodies are usually measured, IgM and IgG. Each of these three different types of tests are positive at different points in the infection cycle.
Here is a description of each of the three types of tests:
1) Polymerase Chain Reaction (PCR) Test
COVID-19 is a RNA virus, so the first step is to use an enzyme called reverse transcriptase (RT) to convert the RNA into DNA. The next step is to amplify the viral DNA and look specifically for target genes unique to the virus. The test sample is usually taken from a nasopharyngeal (back of the nose) swab or pharyngeal (back of the throat). The CDC test is a reverse transcriptase PCR (RT-PCR test), meaning it uses reverse transcriptase to convert the RNA to DNA and then amplifies the DNA so there are enough copies to be detected.
The FDA issued an Emergency Use Authorization (EUA) for the CDC test to be disseminated. An EUA is a legal way for the FDA to approve new drugs, indications, or tests during a declared crisis.
2) Serology Test
Also called antibody tests. Typically this requires getting blood or serum to test. A frequent way of obtaining a sample is through a fingerstick or through venipucture (drawing blood). The two types of antibodies are Immunoglobulin-M (IgM) , a marker that rises early with infection typically within 3-5 days of onset of the infection and stays elevated for several months to a year depending on the infection. The second type of antibody tested is Immunoglobulin-G (IgG), which is a marker of past infection. Typically it rises after the IgM and stays elevated for much longer (usually years) depending on the type of infection. Early in an infection, the IgM is elevated which indicates acute or recent infection. Once IgG is elevated, the infection is far along (probably over 7 to 14 days old).
The biggest risk for the antibody test is getting false negatives, as in the first 3 to 7 days of infection, while someone is very infectious but even asymptomatic, they are proliferating viral particles which would be picked up with a PCR test but read as “negative” in the serology IgM and IgG test because the body has not yet made antibodies to the viral particle (called a false negative test). Therefore if a person has respiratory symptoms or fever or a recent exposure to a known case, the “pretest probability” of this person is having COVID19 is high, and the negative serology test should be ignored and treated as a false negative.
On the other hand, the serology tests are useful, as it can be used as a marker of past infection. Those with low IgM and high IgG to the COVID 19 are those with a past infection and constitute identifying those who have demonstrated the ability to fight the virus. They represent an “immune cohort” who may be the workers who can go back to work and be re-exposed. The one caveat is it is currently not known how protective past immunity is for a recurrent infection and whether past infection completely protects one against a reinfection. In a worse case scenario, it could be like another coronavirus, the common cold, where a past infection does not prevent you from getting another common cold infection in the future. In the best case scenario, COVID-19 does not mutate much , and a past infection confers protection. Those who have elevated IgG may also have serum that could be used to treat who are currently infected. Again, no data yet.
3) Antigen Test
The third type of testing is taken from a blood sample , either obtained from a fingerstick or drawing blood (venipuncture). The COVID-19 virus particle consists of RNA which is covered by a coat of proteins or antigens. Called the viral envelope. This test detects the presence of the antigen using antibodies made against the viral envelope. It is likely to be much less sensitive than the PCR method because the latter is amplifying many copies of the RNA. A positive antigen test is indicative of the presence of viral particles in the bloodstream. A relative few number of manufacturers have made this kind of test and supplies of this will be much more limited.