Because the COVID-19 pandemic has been raging for almost 2 years now, most people have heard of the different viral variants that threaten the effectiveness of full protection with vaccines. This topic can be confusing to anyone who is not familiar with viruses or virology. This article will: 1) help you understand what viral variants are, and 2) explain where they come from. 

Viruses rely on host organisms (e.g., people and/or animals) to make more copies of themselves so that they can infect more hosts. However, hosts typically mount an immune response to clear a virus, which creates a challenge for viruses to overcome. Many viruses have tools that enable them to change their genetic information, which helps them overcome the host’s immune response and transmit and infect other hosts more effectively. These genetically-modified viral forms are called variants. Different viruses change their genetic information at different rates, meaning that certain types of viruses are better at this task than others. The emergence of viral variants also depends on other factors, like how many hosts have already been infected with the virus (the more hosts that have been infected, the greater the opportunity for the virus to produce genetic variants).

You may be wondering, if a variant has different genetic material, then how is it still the same virus? To answer this question, I will use an analogy from the CDC’s informational page. Think of viruses like trees with branches; each branch is slightly different, but they are all part of the same tree. Similarly, each viral variant is just a slightly different version of the same virus, but the majority of the virus is the same. It can be easy to confuse a variant with something that is vastly different from the original virus, but viral variants usually only differ at a handful of places in their genetic material. For example, the SARs-CoV-2 virus, the virus responsible for the COVID-19 disease, has about 4000 nucleotides (i.e., individual building blocks of genetic material) that make up the spike protein region (a region that recognizes receptors on host cells and allows it to enter the cell). The significant variants found in the spike protein are changed in only a few places along this 4000 nucleotide stretch, which corresponds to about 3-9 nucleotide changes; that’s less than a 0.01% change in this region!

Why do variants form?
While viruses make people sick to a varying degree, we are not left defenseless. Hosts have immune systems and immune responses that act to fight off viruses, so many viral copies don’t end up leaving the host because the host is victorious in breaking the viral copies down and flushing them out of their body. Viruses cannot survive without a host, which enables them to make more copies of themselves. So, if the host is good at clearing a particular version of the virus, then the virus will adapt and change its genome to make variants that are better at evading the host’s immune response, leading to more infectious versions of the virus. 

How do variants form?
As mentioned earlier, viruses rely on host organisms to make more copies of themselves. Viruses do this not only by making the machinery from their genome that is needed to make copies, but also by hijacking their host’s machinery to further aid in copying and building new particles. For example, because Sars-CoV-2 uses RNA as its genetic material, the virus makes more copies of its RNA within the host. During this process, some of the RNA nucleotides in the virus can mutate, which could lead to the various changes in spike proteins that produce more infectious variants. As you can imagine, not all nucleotide changes make the virus more infectious; but, we only see the more advantageous variants in the host population because these particular forms of the virus spread more effectively.

Why are scientists keeping an eye on viral variants?
Variants of Sars-Cov-2 can potentially evade the effectiveness of COVID-19 vaccines, which make them a public health concern that needs to be further investigated by scientists. Because Sars-CoV-2 is still spreading, variants can and will emerge that will result in more transmissible forms of the virus, which will ultimately cause more people to become infected with COVID-19. This is especially true for people who have not yet been vaccinated, because their immune systems have no previous protection against Sars-CoV-2 and, therefore, the viral variants are more transmissible. When you are vaccinated, your body builds up antibodies to fight a particular infection. This “immune memory” allows your body to recognize the virus if you are exposed to it again and to mount an immune response more quickly. However, if you are not vaccinated, it takes time for your body to make antibodies to protect you against the virus. Thus, by the time that your body has made enough antibodies to fight off the disease, it may have already set in. For more information about how vaccines and our immune system work, check out my other post here.  

Vaccination is still our best defense against variants, because a high vaccination rate means less viral spread and lower chances for viral variants to emerge. The largest threat to our vaccine immunity is the Delta variant. I’m sure you’ve read about the breakthrough cases of vaccinated people testing positive. It is important to note that, although breakout cases are not unusual, the COVID-19 vaccines are still effective against the Delta variant and are protecting us against severe illness. For more information about the effectiveness of different COVID-19 vaccines against the Delta variant, see the table below, which was adapted from data that were recently published in the New England Journal of Medicine and from preliminary findings in two pre-peer reviewed articles published on medRxiv and bioRxiv. Note that these are preliminary findings, and these results are subject to change as more data are collected. 

Acknowledgements: Thanks to my brother, Dr. Walter Harrington, for his suggestions and edits and to my PhD Advisor, Dr. Tuli Mukhopadhyay, for reading and checking the science described in this post. 

 

References:
Bernal, J. L., Andrews, N., Gower, C., Gallagher, E., Simmons, R., Thelwall, S., Stowe, J., Tessier, E., Groves, N., Dabrera, G., Myers, R., Campbell, C. N. J., Amirthalingam, G., Edmunds, M., Zambon, M., Brown, K. E., Hopkins, S., Chand, M., & Ramsay, M. (2021). Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. New England Journal of Medicine, NEJMoa2108891.

Centers for Disease Control and Prevention (2021). “Published SARS-CoV-2 Sequences.” Centers for Disease Control and Prevention.

National Center for Immunization and Respiratory Diseases, Division of Viral Diseases (2021). “About Variants of the Virus that Causes COVID-19​​.” Centers for Disease Control and Prevention.

National Center for Immunization and Respiratory Diseases, Division of Viral Diseases (2021). “SARS-CoV-2 Variant Classifications and Definitions.” Centers for Disease Control and Prevention.

McNeil, Taylor (2021). “How Viruses Mutate and Create New Variants.” TuftsNow.

Nasreen, S., He, S., Chung, H., Brown, K. A., Gubbay, J. B., Buchan, S. A., Wilson, S. E., Sundaram, M. E., Fell, D. B., Chen, B., Calzavara, A., Austin, P. C., Schwartz, K. L., Tadrous, M., Wilson, K., & Kwong, J. C. (2021). Effectiveness of COVID-19 vaccines against variants of concern, Canada. medRxiv.

Tada, T., Zhou, H., Samanovic, M. I., Dcosta, B. M., Cornelius, A., Mulligan, M. J., & Landau, N. R. (2021). Comparison of neutralizing antibody titers elicited by mRNA and adenoviral vector vaccine against SARS-CoV-2 variants. bioRxiv.

 

Edited by Chloe Holden and Taylor Woodward