Pandemic Part 4: How the Testing Works for COVID-19

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Note: This article continues the Pandemic series which includes Pandemic Part 1: A Primer on the Biology of the SARS-CoV-2 Virus and the Terminology that You are Hearing, Pandemic Part 2: Pandemics of the Past, and Pandemic Part 3: Getting Your Flu Shot and Other Vaccines.

Note: The Pregistry website includes expert reports on more than 2000 medications, 300 diseases, and 150 common exposures during pregnancy and lactation. For the topic Coronavirus, go here.

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The decision on whether you will be tested for SARS-Cov-2, the virus that causes coronavirus disease 2019 (CoViD-19), depends on your symptoms and the possibility that you have come into contact with someone who is infected, or who may be infected. It also depends on the availability of testing and healthcare personnel (those who collect specimens from people and those who process tests and interpret test results.) It would be reasonable to test virtually everybody if test kits and personnel were abundant enough to allow it, but this is not the case. Whether your doctor has sent you for testing, or not, however, you may be curious about how the tests actually work, so let’s take a look at the process at the biological level.

You may have heard that there are several different COVID-19 tests in use by various public health authorities, and also that some medical centers have developed their own tests. This is all true, but the various tests to detect CoViD-19 in patients all fall within a category of tests called reverse transcriptase-polymerase chain reaction RT-PCR assays. What these tests do is to identify the presence of sequences –meaning genes – within viral genetic material. As you may recall from earlier segments of this blog series, the type of genetic material in coronaviruses is called RNA, which is similar to its more famous cousin, DNA, but there are some important differences.

One important difference between RNA and DNA is that a molecule of RNA generally does not persist as long as DNA. The RNA breaks down fairly easily. Consequently, if you detect RNA of a particular genetic sequence, it generally indicates something that is happening close to the present moment. What virus tests based on RT-PCR tell you, therefore, is whether there is an active viral infection at the moment. This is very useful if you are trying to determine if somebody is sick with CoViD-19 and requires treatment and quarantine. However, it is possible to test negative early in the course of the infection. Furthermore, the RT-PCR approach is not very good for determining whether somebody was infected with the virus in the past and fought off the infection. Keep this in mind for later on when we consider some detection tactics other than RT-PCR.

  

Now let’s unpack RT-PCR and see what that’s all about. Rather than being a test that identifies the virus, RT-PCR is more like a process to generate DNA sequences, which then can be tested to see if there is a match. During our second installment of the Pandemic series, we mentioned AIDS, which also is caused by an RNA virus, in this case, human immunodeficiency virus (HIV). Unlike coronaviruses, which simply hijack cells that they invade and use the cellular machinery to reproduce the viral RNA, HIV produces an enzyme that takes the genetic information if its RNA and rewrites it into the language of DNA. In other words it makes DNA genes out of its RNA genes. In the RT-PCR technique, laboratory workers actually use that same type of enzyme to do same process on purpose. They rewrite RNA sequences into DNA sequences so that they can apply another technique to amplify that DNA, which is to say create large amounts of it so that it’s sequences can be tested. Consequently, if a doctor or nurse retrieves some samples from your nose, or if you supply sputum from deeper in your respiratory tract, any SARS-CoV-2 viral particles present in the sample will provide RNA genes. These RNA genes will be copied into DNA genes, which then will be mass-produced, and then tested to determine whether you have CoViD-19.

As noted earlier, since viral particles and RNA don’t last very long, somebody who has fought off a SARS-CoV-2 infection would not test positive for the presence of viral RNA. This means that if the person suffered no symptoms, or suffered only minor cold symptoms, he or she could have spread the virus and health authorities would not know about it. For this reason, scientists are considering introducing other types of tests called immunological tests. There are different kinds of immunological tests, but they all involve antibodies. Scientists can use antibodies to detect a piece of the virus, but they can also use other antibodies, and other types of molecules to determine whether your blood contains antibodies against the virus. When you are exposed to an invading agent, such as a virus, your immune system makes antibodies, and then gradually makes more of that type of antibody, even after the virus is long gone. The problem with both immunological tests and RT-PCR tests is that they are not sensitive enough to detect 100 percent of cases. You can have what’s called a false negative result, meaning that you test negative even though you have been infected. However, use of all forms of testing together would be very powerful and would allow health authorities to track the disease, so stay tuned to this developing story.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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