Expert: Convergent Evolution Occurring Among COVID-19 Variants, With Mutations From Abroad Simultaneously Hitting the US

When looking at the COVID-19 variants, it is increasingly necessary to assess them in terms of the mutations embedded in the variants themselves, explained Scott Gottlieb, MD, former commissioner of the FDA from 2017 to 2019, during a session at the NACDS 2021 Annual Meeting. Ultimately, it’s the mutations that create the risk depending on the type embedded in the variant.

Currently, there are certain mutations and variants that are being followed closely by investigators across the world. For example, the mutation E484K present in the South African variant B.1.351 seems to create a greater risk for reinfection and decrease some of the efficacy of COVID-19 vaccines. This same E484K mutation has also been found to be present in the Brazilian variant P.1 and the New York variant B.1.526.

Gottlieb noted that the Los Angeles variant has a different mutation; however, a mutation present in this variant has been found to increase the fitness of the virus and its propensity to spread and, perhaps, reduce the efficacy of prior immunity.

Additionally, epistasis can occur among multiple variants, which is the combination of variant mutations into new strains that have much different characteristics from the original mutations.

“A mutation that has a certain characteristic and another mutation that has a certain characteristic, when you combine them together in 1 strain, suddenly you get a much different virus that has very unique characteristics that are very dissimilar to any of the characteristics of the individual mutations,” Gottlieb said during the session. “You can get a mutation that does X and a mutation that does Y, and when you put them together, it doesn’t do X and Y, it does Z.”

Epistasis may be what is occurring with the B.1.617 variant found in India, Gottlieb explained. In this variant, there are 2 mutations embedded within it that are of the greatest concern. One of these is similar to the E484K mutation but is called the E484Q mutation, whereas the other mutation is similar to the mutation of concern embedded in the Los Angeles variant. In the B.1.617 variant, both of these new mutations are present.

“That seems to be responsible for the out of control epidemic that is underway in India right now. The incidence of that B.1.617 mutation has gone from about 20% of cases 2 months ago to over 80% of cases at the beginning of this month, which means it must be higher right now because we only have data as of the beginning of April,” Gottlieb said during the session.

However, in order for the United States to be affected by the variants from India, South Africa, or Brazil, it is not necessary for the variants themselves to be transported into the country from abroad. Instead, convergent evolution is occurring, which is where the variants are growing up simultaneously in multiple parts of the world.

“They’re happening spontaneously. So, you don’t necessarily need them to be imported—they’re happening right here,” Gottlieb said during the session. “That’s why it’s important to get control of the virus.”

Some investigators in the field are considering that as the B.1.1.7 variant from the UK becomes the prevalent strain, it’s going to crowd out some of these other mutations. This may happen because the B.1.1.7 variant is similar enough to other mutations that people who were infected with B.1.1.7 will have some cross-immunity to the other strains.

Additionally, some investigators are considering that the virus may reach a fitness level whereby multiple mutations have evolved at once, leading the virus to not evolve at the same pace as it did initially. This may mean that the rate of change in the virus may start too slow.

“It has a certain repertoire, it has a certain range of things that it was going to do to try to evade our immunity, and if there are 20 things that it can do, it may have already done 15 of them,” Gottlieb said during the session.

In this way, COVID-19 may not be like the flu, in which the virus continuously adapts in order to stay ahead of our immunity to it, Gottlieb explained.

“It did a lot of evolution very quickly because of the intense pressure it was under and its wide spread,” Gottlieb said. “Now, it’s reached a new fitness level, and it’s rate of change is going to start too slow.”

REFERENCE

Anderson SC, Paley L, Keyes R, Gottlieb S. Business Program I. National Association of Chain Drug Stores Annual Meeting 2021; April 26, 2021; virtual. Accessed April 28, 2021.