Massive number of new COVID-19 infections, not vaccines, main driver of new coronavirus variants



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The rise of variants of the coronavirus has highlighted the enormous influence of evolutionary biology on daily life. But how mutations, chance, and natural selection produce variants is a complicated process, and there has been a lot of confusion about how and why new variants emerge.

Until recently, the most famous example of rapid evolution was the story of the Pepper Moth. In the mid-1800s, factories in Manchester, England began to cover the habitat of the sooty butterfly, and the butterfly’s normal white coloration made them visible to predators. But some butterflies had a mutation that made them darker. Since 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 infectious disease epidemiologist at the University of Pittsburgh who work together to track and control the evolution of pathogens. Over the past year and a half, we have been following closely how the coronavirus has acquired different mutations around the world.

It’s natural to wonder whether highly effective COVID-19 vaccines lead to the emergence of variants that escape the vaccine – like pepper mites escaping birds that hunt them. But with just under 40% of people globally having received a dose of a vaccine – just 2% in low-income countries – and nearly a million new infections occurring globally every day, emergence of new, more contagious variants, such as delta, is driven by uncontrolled transmission, not by vaccines.

An open coronavirus showing an RNA strand.

An open coronavirus showing an RNA strand.

How a virus mutates

For any organism, including a virus, copying its 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 replicates, about 3% of new virus copies have a new random error, also 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 overshadowed by the much larger number of viruses that are identical to the strain that triggered the infection.

Almost all of the mutations that occur are harmless problems that don’t change how the virus works – and others actually harm the virus. A small fraction of the changes can make the virus more infectious, but these mutants must be lucky too. To give birth to a new variant, she must successfully jump to a new person and breed many copies.

Transmission is the big bottleneck

Most viruses in an infected person are genetically identical to the strain that triggered 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 virus is passed from its original host to another person.

And even if a new mutant causes infection, mutant viruses usually outnumber non-mutant viruses in the new host and are usually not passed on to the next person.

The low probability that a mutant will be transmitted is called a “population bottleneck”. The fact that only a small number of viruses trigger the next infection is the critical random factor that limits the likelihood of new variants appearing. The birth of each new variant is a fortuitous event involving a copy error and an unlikely transmission event. Of the millions of copies of coronavirus in an infected person, it is unlikely that a fitter mutant would be among the few to spread to another person and amplify into a new variant.

Close-up of a large tower-shaped structure attached to a small receiver on a cell.

Close-up of a large tower-shaped structure attached to a small receiver on a cell.

How do new variants emerge?

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

Many researchers are studying which mutations lead to more transmissible versions of the coronavirus. It turns out that the variants tend to 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 still unvaccinated, susceptible hosts are rarely in short supply. Thus, natural selection will promote mutations that can exploit all these unvaccinated people and make the coronavirus more transmissible.

Under these circumstances, the best way to slow the progression of the coronavirus is to reduce the number of infections.

Vaccines stop new variants

The delta variant has spread around the world and the next variants are already on the rise. If the goal is to limit infections, vaccines are the answer.

Although vaccinated people can still be infected with the delta variant, they tend to experience shorter and milder infections than unvaccinated people. This dramatically reduces the chances that any mutated virus – either the one that makes the virus more transmissible, or the one that could allow it to pass immunity to vaccines – will jump from person to person.

Eventually, when almost everyone has some immunity to the coronavirus through vaccination, viruses that break that immunity could gain a competitive advantage over other strains. It is theoretically possible that in this situation, natural selection will lead to variants that can infect and cause serious illness in those vaccinated.

However, these mutants have yet to escape the population bottleneck. Vaccine-induced immunity is unlikely to be the major contributor to the emergence of variants as long as there are many new infections. It’s just a numbers game, and for now, the modest benefit the virus would derive from the vaccine breakout is overshadowed by the vast possibilities of infecting unvaccinated people.

The world has already witnessed the relationship between the number of infections and the increase in mutants. The coronavirus remained essentially unchanged for months until the pandemic got out of hand. With relatively few infections, the genetic code had limited possibilities to mutate. But as the infection clusters exploded, the virus rolled the dice millions of times and some mutations produced more fit mutants.

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

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This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Vaughn Cooper, University of Pittsburgh and Lee Harrison, University of Pittsburgh.

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Vaughn Cooper is a member of the board of directors of the American Society of Microbiology and co-founder and shareholder of Microbial Genome Sequencing Center, LLC.

Lee Harrison does not work, consult, own stock, or receive funding from any company or organization that would benefit from this article, and has not disclosed any relevant affiliation beyond his academic position.

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