News and Views — COVID-19: The Vaccine Versus the Variants

Media reports have extensively covered COVID-19 variants regarding where they are spreading, whether they are more severe, and whether the vaccines still protect against them. These issues are important for individuals and individual risk, but an important message that has gotten less attention is why the variants are important from a populational perspective, and why this, too, contributes to individual risk.

Viral variants are normal

Virologists were not surprised when COVID-19 variants started to arise given that viruses often change when they replicate. Evolutionary survival means always having a population of susceptible people to infect. As more people become immune to a virus, the pressure on the virus to survive increases. As described in this reading passage from the Vaccine Makers Project materials, changes to the structure of a virus is one of multiple ways that pathogens seek to remain relevant. The changes improve the ability of the virus to cause infections (e.g., increase transmissibility or allow infection of more people), render previously immune people susceptible, or both. While most changes do not result in viable mutants, a few will, and these will be versions that go on to spread, often referred to as “escape mutants.”

To be successful, escape mutants or variants must have a structural alteration that maintains functional stability of the virus. For example, in the case of SARS-CoV-2, a change to the spike protein that evades existing antibodies cannot also cause the virus to lose its ability to bind to the ACE-2 receptor. As such, individual changes are often small. But over time, such changes may accumulate resulting in identifiably different characteristics, making the virus more common and less susceptible to existing treatments or vaccine-induced immunity.

The Centers for Disease Control and Prevention (CDC) has three classifications for current COVID-19 variants based on characteristics including receptor binding, response to neutralizing antibodies or existing treatments, possible diagnostic impact, and potential to be more easily transmitted or cause more severe disease. The classifications include:

• Variants of interest (VOI), which have the potential to develop one or more of the above characteristics.
• Variants of concern (VOC), which show evidence of having one or more of the above characteristics.
• Variants of high consequence (VOHC), which show clear evidence of significantly decreased response to neutralizing antibodies generated by immunization or natural infection with the common circulating strains.

Currently, no VOHC are circulating in the U.S., but as of early April 2021, five VOC have been identified and continue to be closely monitored:

• B.1.1.7 originated in the United Kingdom. It spreads more rapidly and is likely more severe.
• P.1 originated in Japan and Brazil. This variant is relatively resistant to neutralizing antibodies following vaccination or infection as well as to monoclonal antibodies used for treatment.
• B.1.351 originated in South Africa. This variant spreads more rapidly and is relatively resistant to neutralizing antibodies following vaccination or infection, as well as monoclonal antibodies.
• B.1.427 originated in the U.S. This variant spreads more rapidly, although not as much as B.1.1.7 or B.1.351, and it is less susceptible to neutralizing antibodies from vaccination or infection. It is also less susceptible to some, but not all, therapeutics currently authorized for use in the U.S.
• B.1.429 originated in the U.S. This variant has similar characteristics to B.1.427 in terms of its spread and susceptibility.

The CDC offers an easy-to-use table summarizing the current information on this page of their website. The page also shows a table with VOI.                                                        

The role of vaccination

Viruses seeking evolutionary survival only care that they have a population to infect. As such, they will continue to spread and change as long as they have the opportunity to do so. With each infection, the virus gets another chance to change and “improve itself” in some way that will increase the pool of susceptible people. For humans, this means that if the virus succeeds, someone who was once immune may again become susceptible.

With this in mind, decreasing the number of chances the virus has to increase the pool of susceptible people is where herd immunity becomes important. If someone cannot be infected, the virus cannot replicate in them and begin to mutate. That person represents a red light or stop sign as far as viral spread goes. The more red lights in a community, the slower the viral spread and the fewer chances for the virus to regain the upper hand.

Because people can only become immune in two ways, through infection or vaccination, and infection comes with risks for severe disease and death, vaccination is safer. It is also a better method for limiting viral replication, given that infection offers the virus more chances to improve itself. Further, since severe infections often employ multiple treatments, including antibody-based types, surviving escape mutants may be more likely to evade treatments that work against current versions of the virus.

Conversations to help individuals understand how population-based developments may affect them are critical, particularly given the reported levels of vaccine hesitancy. When an individual decides not to get a COVID-19 vaccine, they offer an opportunity for the virus to continue spreading. The more the virus replicates, the more likely that variants arise which do not respond to existing immunity and the greater the chance that a previously immune person will again become susceptible. As such, individual choices affect the outcome for everyone. The race is not among the vaccinated versus the unvaccinated; it is humans against the virus. Each susceptible person represents a green light for the virus to again try to gain the upper hand.

Additional resources

• Proportion of each variant in U.S. cases
• Global monitoring of variants