As we continue to navigate the daily changes regarding our response to the COVID-19 pandemic, I have taken a moment to pause and reflect on the person I would like to see emerge on the other side of this. One gift that has been presented to me - is time. While I am still working, many of the other day-to-day tasks and activities are on hold. It is this time that has helped me to understand there are areas where I can gain more knowledge and try to help to my family, friends, and co-workers understand the finer points of the current pandemic.
All too often, it is the seemingly miniscule pieces of information that can reframe a person’s perspective of a stressful or threatening situation. It is also crucial that each of us takes every opportunity to bend ourselves before the world does to sharpen our response to difficult situations. I decided that I needed to improve my understanding of how a virus functions. Except, I needed to explain this to my family with normal words lol.
A virus is very small, mostly because they are not complete cells. A virus is made up of genetic material and some proteins. To say it very simply, a virus uses the host cell’s “supplies” and “machinery” to reproduce itself. Think of this like a flash drive for your computer. It can not replicate itself unless it has a computer (host).
The virus will remain dormant until it can hijack a specific host cell. Once it makes its way in, the first goal is to replicate. Hidden in a cell, the immune system may not notice this for a little while.
Alright Mike, what's the difference between a DNA and RNA Virus?
DNA viruses are made up of DNA and proteins (that’s it!), and the amount of DNA is much less than in a human cell. The host cell converts the DNA into RNA (transcription) and then the host cell’s ribosome converts the RNA into protein (translation).
The nasty little DNA virus uses the host cell to replicate its DNA. Psh.. unreal.
This is the same process that a healthy cell would be doing naturally, only with the host DNA, not the virus DNA. The viral DNA and proteins the host cell made are then assembled into more viruses. The host cell bursts or the virus transports itself out of the cell, which allows it to spread to neighboring cells. Examples of DNA viruses are herpes and various poxviruses.
SARS-CoV-2 is an RNA virus. An RNA virus enters the host with genetic material in the form of RNA and a special helper (reverse transcriptase for some if you’re curious). SARS-CoV-2 has a unique protein spike on its surface which facilitates entry of the virus into the cell.
The cell is once again hijacked, the only difference is that the RNA is incorporated into the host cell’s DNA using the reverse transcriptase. This is not a super accurate process. Small errors made at this point contribute to the high mutation rates seen with RNA viruses.
Now, much like Cousin Eddie, they have made themselves right at home and use the host cell to complete their replication. Another slight difference in SARS-CoV-2 is that it does not use reverse transcriptase but follows a similar process using the host cell. Influenza, measles, and coronaviruses are just a few examples of RNA viruses familiar to us.
The next line of defense, if gratuitous hand washing and social distancing failed us, is our immune system. We need to have a basic understanding of this in order to explain the testing related to SARS-CoV-2. Our immune system makes antibodies (immunoglobulins) that are used to flag the antigens on the invading substance (i.e. like that protein spike we talked about on the surface of SARS-CoV-2).
These flags then elicit an immune response from different types of immune cells. This response is designed to limit viral replication and eliminate infected cells. The two types of antibodies most important to understand testing are IgG and IgM. IgM is first produced in response to the virus, while IgG is present toward the end when we have developed immunity.
The second portion of this blog will discuss some basic concepts of testing for SARS-CoV-2. Like myself, I am sure that many of you have heard about testing on the news with variable understanding of some of the core concepts. Two types of tests in use are:
Polymerase Chain Reaction (PCR): Testing that is looking for the virus, like PCR, uses samples from nasal/throat swabs – and sample collection and can be quite unpleasant! For PCR testing, the sample is prepared using special solvents to remove the proteins and to extract the RNA. Now a special “cocktail” of enzymes is added to convert this to DNA. This DNA is subjected to several heat cycles and if the DNA sequence matches a known sequence (i.e. the viral genetic sequence), there will be amplification of this DNA sequence and it will produce a “signal” as positive. These heat cycles are performed 25, 30, even 40+ times to complete the test! Perhaps this helps explain why it takes a while to get results! Once the test is complete, quantified measurement of the viral load can occur. Some tests are considered RT-PCR. This means that they are “Real Time” and can give results after each heat cycle.
Immunoassay: This is qualitative (Positive or Negative) for the presence of IgG and IgM. The primary type emerging is the cassette style, similar to a pregnancy test. Blood is added to a well and moved along the cassette through capillary action. This will create a positive or negative response for the control, IgG, and IgM windows. These tests are often more convenient than PCR but are not generally as sensitive or specific.
PCR is looking for viral genetic material and can determine the amount of virus in the host or viral load, while the immunoassay is focused on antibodies and is looking for IgG or IgM made by the patient in response to infection.
It is important to remember that many of these tests are still under emergency use authorizations from FDA, therefore, FDA approved data on sensitivity and specificity is generally not available. As with any diagnostic test, the result can provide valuable information but is only a portion of a complete clinical picture. The testing and treatments are constantly changing in response to this pandemic. If you have any interest in the latest studies related to this please go to clinicaltrials.gov for complete up to date lists. I hope that you have found this information to be helpful. If you would like more information on these subjects as well as some treatment information and vaccine development, we have a link below to a recording I did with Vivian Cintron, Ph.D. She has a great background in this field and was an absolute joy to talk with. She will tell you more about herself in the beginning and we will take a deeper dive into these subjects and more. This was a great opportunity and I hope that you can enjoy it, too. I have links to references throughout the blog. I have also included a PDF with some information on current vaccines in development. Potential-Vaccines