What Is Causing All These New Coronavirus Variants? Is It the COVID–19 Vaccines?

The sheer number of active coronavirus infections offers plenty of opportunities for the emergence of mutations and the emergence of new variants.

Huge numbers of new COVID-19 infections are the leading cause of new coronavirus variants.

The emergence of coronavirus variants has highlighted the enormous impact of evolutionary biology on everyday life. But how mutations, random chance and natural selection produce variants is a complicated process and there has been much confusion about how and why new variants arise.

Until recently, the most famous example of rapid evolution was the story of the peppered moth. In the mid-1800s, factories in Manchester, England, began covering the moth’s habitat with soot, and the moth’s normal white color made them visible to predators. But some moths had a mutation that made them darker. Because they were better camouflaged in their new world, they were able to evade predators and reproduce more than their white counterparts.

We are an evolutionary biologist and an infectious disease epidemiologist at the University of Pittsburgh who work together to monitor and control the evolution of pathogens. For the past year and a half, we have been closely monitoring how the coronavirus has acquired various mutations around the world.

It’s natural to wonder if highly effective COVID-19 vaccines are leading to the emergence of vaccine-avoiding variants — such as dark-peppered moths dodging the birds that preyed on them. But with just under 40% of the world’s people who have received a dose of a vaccine — just 2% in low-income countries — and nearly a million new infections happening worldwide every day, the emergence of new, more contagious variants, such as delta, are driven by uncontrolled transmission, not vaccines.

Coronaviruses use RNA to store information and small changes in that genetic code can lead to new virus strains.

How a virus mutates

For any organism, including a virus, copying the genetic code is the essence of reproduction, but this process is often imperfect. Coronaviruses use RNA for their genetic information and copying RNA is more prone to errors than using DNA. Researchers have shown that when the coronavirus multiplies, about 3% of new virus copies have a new, random error, known as a mutation.

Each infection produces millions of viruses in a person’s body, leading to many mutated coronaviruses. However, the number of mutated viruses is dwarfed by the much greater number of viruses that are the same as the strain that initiated the infection.

Nearly all the mutations that occur are harmless glitches that don’t change the way the virus works – and others are even harmful to the virus. A small fraction of the changes can make the virus more contagious, but these mutants also have to be lucky. To arrive at a new variant, it must successfully jump to a new person and replicate many copies.

The bottleneck of transmission is what limits a new variant’s ability to infect another person. Credit: Vaughn Cooper via Biorender, CC BY-ND

Transmission is the main bottleneck

Most viruses in an infected person are genetically identical to the strain that caused the infection. It is much more likely that one of these copies — not a rare mutation — will be passed on to someone else. Research has shown that almost no mutated viruses are transmitted from their original host to another person.

And even if a new mutant causes an infection, the mutant viruses are usually outnumbered by non-mutant viruses in the new host and are usually not transmitted to the next person.

The small chance of a mutant being transmitted is called the ‘population bottleneck’. The fact that only a small number of viruses initiate the next infection is the critical, random factor that limits the chance of new variants emerging. The birth of each new variant is a random event with a copy error and an unlikely transmission event. Of the millions of coronavirus copies in an infected person, a fitter mutant is unlikely to be one of the few that spreads to another person and is amplified into a new variant.

Mutations have changed the structure of the spike protein, shown in red, and have made the coronavirus better able to infect cells using the ACE2 receptor, shown in blue. Credit: Juan Gaertner/Science Photo Library

How do new variants arise?

Unfortunately, the uncontrolled spread of a virus can overcome even the smallest bottlenecks. While most mutations have no effect on the virus, some can and have increased the contagiousness of the coronavirus. If a rapidly spreading species can cause a large number of COVID-19 cases somewhere, it will outnumber less contagious species and generate a new variant – just like the delta variant did.

Many researchers are investigating which mutations lead to more transmissible versions of the coronavirus. It turns out that variants often have many of the same mutations that increase the amount of virus an infected person produces. With more than a million new infections occurring every day and billions of people who have not yet been vaccinated, there is rarely a shortage of susceptible hosts. So natural selection will favor mutations that can exploit all these unvaccinated people and make the coronavirus more transmissible.

Under these circumstances, reducing the number of infections is the best way to limit the evolution of the coronavirus.

Vaccines stop new variants

The delta variant has spread all over the world and the following variants are already emerging. If the goal is to limit infections, vaccines are the answer.

While vaccinated people can still become infected with the delta variant, they tend to have shorter, milder infections than unvaccinated individuals. This greatly reduces the chance that a mutated virus — either one that makes the virus more transmissible or one that could make it past vaccine immunity — jumps from one person to another.

Ultimately, when almost everyone has some immunity to the coronavirus through vaccination, viruses that break this immunity can gain a competitive advantage over other strains. It is theoretically possible that natural selection in this situation will lead to variants that can infect and cause serious illness in vaccinated people. However, these mutants still have to escape the population bottleneck.

For now, it is unlikely that vaccine-induced immunity will be the main player in the emergence of variants, as many new infections are occurring. It’s just a numbers game. The modest benefit the virus would have in evading vaccines is dwarfed by its vast potential to infect unvaccinated people.

The world has already witnessed the relationship between the number of infections and the emergence of mutants. The coronavirus remained essentially unchanged for months until the pandemic spiraled out of control. With relatively few infections, the genetic code had limited ability to mutate. But when infection clusters exploded, the virus rolled the dice millions of times, and some mutations produced fitter mutants.

The best way to stop new variants is to stop their spread, and the answer to that is vaccination.

Written by:

Vaughn Cooper – Professor of Microbiology and Molecular Genetics, University of Pittsburgh Lee Harrison – Professor of Epidemiology, Medicine and Infectious Diseases and Microbiology, University of Pittsburgh

This article was first published in The Conversation.