How Do the COVID-19 Coronavirus Tests Work?

There are two kinds of tests necessary for a complete picture of your COVID-19 coronavirus infection status: genetic and immunoglobulin.

Tests for coronavirus may use two methods to detect the SARS-CoV-2 virus, the cause of COVID-19 disease, a debilitating and potentially deadly viral pneumonia. 

The tests are: 

• genomic detection-based (molecular)
• immunoglobulin detection-based (serology)

The first and most prevalent method to detect the virus in individuals is based on detecting genetic material specific to SARS-CoV-2 viruses in a person’s nasopharyngeal secretions.

Although tests kits have a wide variation in their procedures (swabs of oral and/or of nasal surfaces, differences in solutions to transfer the swabbed tissue to, time and place to run the subsequent test reagents, for example), they all use methods that detect a specific part of the viral genome.

Here is an example of how one test system accomplishes this:

• Swabbed tissue is loaded into a standard reaction vial
• Reagents (the general term for additional chemicals needed in such tests) break open viruses to expose viral genome (RNA) to other reagents like synthesized RNA that binds to a specific small part of the viral RNA
• This small bound-up strand of viral genome and reagent is then replicated many times (in some tests, up to a billion times!) over minutes to hours
• Then, at the same time, another reagent specifically binds to each replicated genetic complex.
  • This reagent has a bounded marker that when enough replicated complexes are made, the machines can detect the attached marker. 
  • For example, the marker may be designed to glow with fluorescence, which the machine can pick up on its sensors.
• Depending on how many viruses are present in the sample, positive results may occur (depending on the test used) in minutes to days
• Conversely, if the test detects no viral material after a fixed time (minutes to days), the result is a negative test

The qualitative results from these tests are either the person is infected with SARS-CoV-2 and considered to be able to transmit the disease (a positive test) or is negative for the virus. 

This test cannot tell whether a person is immune from past infection or has yet to be exposed and is still in danger, however.

Immunoglobulin detection tests are based on the qualitative detection of IgM and IgG that are specifically generated by the body in response to SARS-CoV-2 infection. 

IgM is usually the first, specific antibody type generated by the body in response to infection. Then, the IgG antibody type is generated and replaces IgM as the predominant antibody in the response to infection. 

IgM and IgG fight infections by targeting specific antigens on the surface of the SARS-nCoV-2 virus. 

In general, immunoglobulin tests use specific viral antigens to detect the IgM and/or IgG antibodies against those antigens.

Here is a sample of how the test works:

• Collect 2-3 drops of fresh blood/serum or plasma and place it in a sample container and place 2-3 drops of provided buffer in the same container (cassette)
• The cassette allows the diluted sample to move through the cassette by capillary action
• The cassette has labeled SARS-CoV-2 antigen that may  bind chemically with either IgM or IgG; thus, forming an antigen/antibody complexes of antigen/IgG and/or antigen/IgM   
• After that reaction, the antigen/antibody product passes over anti-IgM and anti-IgG antibodies that are immobilized in a line within the cassette
• The anti-IgM and/or anti-IgG then will capture the specific complex and signal a result (a red line) if either complex is bound to the immobile anti-IgM or anti-IgG 
• The results need to be read after 10 minutes and no more than 15 minutes (the test resembles a home pregnancy test in this respect.) 
• A third line is a control line; it indicates that the test is working properly

A total of three detection lines are possible, the control with (C) line appearing when sample has finished flowing through the cassette, indicating the test is complete. 

The following are what the results mean:

• Negative Result: If only the quality control line (C) appears and the detection lines G and M are not visible, then no novel coronavirus antibody has been detected and the result is negative.
• Positive Result, IgM only: If both the quality control line (C) and the detection line M appears, then the novel coronavirus IgM antibody has been detected and the result is positive for the IgM antibody.
• Positive Result, IgG only: If both the quality control line (C) and the detection line G appears, then the novel coronavirus IgG antibody has been detected and the result is positive for the IgG antibody.
• Positive Result, IgG and IgM: If the quality control line (C) and both detection lines G and M appear, then the novel coronavirus IgG and IgM antibodies have been detected and the result is positive for both the IgG and IgM antibodies.

Immunoglobulin tests for COVID-19 cannot confirm the presence of the virus in your system. It can only tell whether you have been exposed in the past or if you have never been exposed to SARS-CoV-2. Consequently, it should only be used alone as a screening test and should be used in tandem with a genetic-based test to determine a complete status. Genetic testing is the gold standard for COVID-19 diagnosis.

The goals of mass testing are to accurately test most people to determine their status in relation to this infectious disease so they can go forward with their lives.

The large majority of people fall into the categories below:

• People that have COVID-19, (with or without symptoms),
• Some results may also show whether or not the infected patient's immune system seems to be responding well or poorly to the virus
• People not yet exposed to the virus,
• People that have immunologically responded and have a good antibody response (and possibly be an antibody donor to help fight the virus in other people),
• People able to go back to work and be unaffected by the virus and currently not transmitting the virus, even if they were positive for the virus at some point in the past.

The results of these two different COVID-19 tests, run in tandem, can determine the person’s status as described below:

• A positive gene test means the person is actively shedding virus and is contagious;
• A negative gene test means the person is not shedding virus;
  • With two negative genetic tests done 24 hours apart, according to CDC, the person is not contagious (shedding virus), meaning the person either has never been infected or (if previously infected) is no longer shedding virus.
• If immunoglobulin tests are all negative, the test indicates the person has not been recently exposed to the COVID-19 virus.
• If the test shows only IgM, the person is likely in the early stage of the virus infection;
• If IgM and IgG are positive, the person is likely in the middle stage of infection,
• If the person is only positive for IgG, then the person is either over the infection or in its last stage.

In most cases, independent of the results of the immunoglobulin tests, the test for the viral genes still must be administered to confirm infection status.