The Latest on COVID-19 Variants

Feb 24, 2021

by ETHAN LEVY, PA-C, MPAS, MSESS, AT-C, CSCS

Ethan Levy, Physician's Assistant at Wholistic Pediatrics & Family Care

Please note, all information discussed in this article is evolving very rapidly. Wholistic Pediatrics & Family Care will continue to do our best to provide timely, important updates and developments.

It has been widely publicized that many different variants of SARS-CoV-2 (which causes COVID-19) have emerged, most of which are present in the United States. In this article, I will briefly discuss the typical process of viral mutations, the important variants that have been identified thus far, and the significance of this natural phenomenon with its potential impacts on the pandemic.

Understanding Virus Variants

Variants are both expected and inevitable among any virus, especially one that circulates globally, infects large numbers of people, and is exposed to one’s immune response for weeks at a time. Additionally, the longer a virus spreads through large populations without robust preventative measures being engaged (e.g., wearing face masks, physical distancing, optimizing immune systems through healthy habits, and vaccination), the more opportunities that virus has to mutate. The faster herd immunity is obtained, the less likely the virus will continue to mutate and spread. To further complicate things, certain therapeutic interventions that may hasten one’s recovery without rapidly eradicating the virus may encourage mutations to occur as the virus has time to adapt to the treatment. This may have been the case with IV monoclonal antibody therapy, which involves administering an infusion of a specific antibody that attacks the spike protein of SARS-CoV-2 and reduces the virus from entering the cells to replicate the viral load.

As stated above, it is “normal” and expected for a virus to undergo mutations, produce variants, and even develop new strains over time. When a virus infects a host, it uses that person’s cells to generate copies of itself. Some of these copies will contain errors and mutations. The process of natural selection allows the variants with the greatest advantage towards survival and infectivity to eventually become the dominant strain in circulation.

In many cases, the acquired mutations do not offer the virus any advantage and are clinically insignificant. In some cases, they may even be counterproductive to the virus or lead to its ultimate failure to circulate widely. An example of this would be a mutation that allows the virus to be capable of causing such severe disease that it prematurely kills the infected person and the virus, which prevents it from spreading effectively.

A “smart virus” if you will, can attain a sweet spot for itself by being highly contagious, including during a pre-symptomatic or asymptomatic state, while not being so deadly as to rapidly incapacitate or kill most of the people who are infected. This would increase the chances the virus will continue to spread.

Current SARS-CoV-2 Variants

As of this writing, three variants are of particular concern and being monitored closely. The B.1.1.7 strain originated in the United Kingdom, with variants in the receptor-binding domain of the spike protein (the part of the spike protein that adheres to a human cell prior to invading that cell), is associated with a more rapid and efficient transmission rate. It has been suggested that this strain could be up to 50-70% more contagious and may infect adults and children more equally. It has also been suggested this variant is likely to become dominant in the United States by the end of March. Early studies suggested this variant was not more likely to cause more severe disease, but other more recent studies are indicating otherwise, possibly 30% deadlier. [1]

The B.1.351 South African variant, like the U.K. variant, “contains a mutation known as N501Y which is believed to make the virus more contagious than older variants.” [10] The South African variant also contains other mutations of concern, including E484K and K417N. These two mutations are thought to explain why the South African variant appears to be better able to evade neutralizing antibody responses by the body”. [1, 2]

The third variant of primary concern, first found in Brazil and known as P.1, contains three mutations (E484K, K417T, and N501Y) in the spike protein receptor binding domain. Some evidence suggests this variant may be more transmissible and also impact the ability of antibodies to recognize and neutralize the virus. There is also concern this variant may have a better chance of causing reinfection, as suggested by its high infection rate in a Brazilian city that had already been highly impacted by the virus. [1, 2]

In addition to the three primary variations discussed above, seven additional variants with a mutation called Q677P originating in the U.S., and a newly identified variant in Japan that has affected 100 people, are currently being studied in regard to their clinical implications. We will likely see more information about these as data emerges.

COVID-19 Vaccines and the Variants

Both the Pfizer and Moderna mRNA vaccines are polyclonal and, therefore, cause the body to produce multiple antibodies directed against different parts of the spike protein. As a result, the virus would need to undergo very significant changes affecting multiple parts of the spike protein to truly evade the body’s protective immune response that is produced once interacting with the spike protein that is made from the mRNA. [1, 9]

According to research presented by Pfizer / BioNTECH, the Pfizer vaccine seems to be protective against both the U.K. variant and, to a lesser extent the South African variant. Laboratory studies showed the Pfizer vaccine produced about one-third of the antibodies against the South African variant compared to the original strain; however, this level was enough to neutralize the virus. [2, 3]

The Moderna vaccine shows protection against the U.K. strain, with reduced protection from the South African strain by producing about one-sixth fewer neutralizing antibodies as compared to those against the U.K. variant. This prompted the company to take a formal stance that “protection remains undetermined,” although they stated that “levels of neutralizing antibodies remain high enough that should confer immunity”. [2, 4]

It is difficult to make a head-to-head comparison, but essentially both the Pfizer and Moderna vaccines should be effective against the U.K. variant, and at least partially effective against the South African variant. Research is ongoing about the impact each of these vaccines has on the Brazilian variant, but it has been suggested there may be reduced protection. [5] Both companies have indicated they can effectively tweak, update, and/or add boosters in response to these emerging variants. As of the latest research, the AstraZeneca vaccine (which is a viral vector DNA vaccine, not the mRNA type used by Pfizer and Moderna), has not demonstrated efficacy against the South African B.1.351 strain. [6]

Where This Leaves Us

As one can see, the SARS-CoV-2 virus is not going down without a fight. All viruses circulate, invade, infect, multiply, and survive. Along the way, numerous mutations are born, the virus adapts to its environment, and evolution takes place.

The SARS-CoV-2 virus has a genome approximately 30,000 nucleotides (RNA letters) long, and tends to mutate a bit slower than other viruses due to its robust internal error-checking domain. [7, 8] The vast majority of mutations of the large and complex genome that make up a virus should not necessarily induce a state of panic because they are either clinically irrelevant or detrimental to the virus.

Given enough time, however, and with a global population of infections, the process of natural selection can potentially induce strains that are more transmissible or virulent, variants more capable of evading antibodies and diagnostic testing accuracy.

Scientists agree the most effective ways to slow the spread and generation of new coronavirus variants include the effective and collaborative use of various tools. These include surveillance efforts, physical distancing, wearing masks properly, optimizing nutrition and the immune system, and the implementation of safe and effective vaccines and therapeutics.

Sources:

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