The Coronavirus Is Mutating. What Does That Imply for Us?

Just as vaccines were beginning to offer hope for a way out of the pandemic, British officials issued an urgent warning on Saturday of a so-called highly contagious new variant of the coronavirus circulating in England.

Citing the rapid spread of the virus in London and the surrounding area, Prime Minister Boris Johnson imposed the country’s strictest lockdown since March. “If the virus changes its method of attack, we will have to change our method of defense,” he said.

A similar version of the virus has emerged in South Africa, which scientists who discovered it have one of the mutations seen in the British variant, according to scientists who discovered it. This virus was found in up to 90 percent of the samples whose genetic sequences had been analyzed in South Africa since mid-November.

Scientists are concerned about these variants, but not surprised by them. Researchers have found thousands of tiny changes in the genetic material of the coronavirus that has hopped around the world.

Some variants become more common in a population only through luck, not because the changes somehow charge the virus. However, because vaccinations and increased immunity make it harder for the pathogen to survive in human populations, researchers also expect the virus to acquire beneficial mutations that make it easier to spread or evade detection by the immune system.

“It’s a real warning that we need to take a closer look,” said Jesse Bloom, evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle. “Certainly these mutations will spread, and definitely the scientific community. We need to monitor these mutations and characterize their effects.”

The British variant has around 20 mutations, including several that affect how the virus binds to and infects human cells. These mutations could allow the variant to replicate and transmit more efficiently, said Muge Cevik, an infectious disease expert at the University of St Andrews in Scotland and a scientific advisor to the UK government.

The estimate of higher transferability – British officials said the variant was up to 70 percent more transferable – is based on the modeling and has not been confirmed in laboratory experiments, added Dr. Cevik added.

“Overall, I think we need a little more experimental data,” she said. “We cannot completely rule out that some of this portability data is related to human behavior.”

In South Africa too, scientists quickly discovered that human behavior triggered the epidemic, not necessarily new mutations, the effects of which on transmissibility had yet to be quantified.

The UK announcement also raised concerns that the virus could evolve to become resistant to the vaccines that are being rolled out. The concerns focus on a few changes in the viral genetic code that may make it less susceptible to certain antibodies.

However, several experts warned caution, saying it would take years – not months – for the virus to develop to the point where current vaccines become impotent.

“Nobody should worry that there will be a single catastrophic mutation that will suddenly make all immunity and antibodies unusable,” said Dr. Bloom.

“It will be a process that takes place over a period of several years and requires the accumulation of multiple viral mutations,” he added. “It’s not going to be like an on-off switch.”

Like all viruses, the coronavirus is a shape shifter. Some genetic changes are unimportant; others can give him an advantage.

Scientists fear the latter possibility, in particular: vaccinating millions of people can put tremendous pressure on the virus to become resistant to the immune response, pushing back the global battle for years.

There are already small changes in the virus that have occurred independently of one another several times around the world, suggesting that the mutations are helpful for the pathogen. The mutation that affects antibody susceptibility – technically known as the 69-70 deletion, which means that letters are missing from the genetic code – has been seen at least three times: in Danish mink, in people in the UK, and in an immunocompromised patient who became much less sensitive to convalescent plasma.

“This thing transmits, it acquires, it keeps adapting,” said Dr. Ravindra Gupta, a virologist at the University of Cambridge, who last week detailed the recurring genesis and spread of the deletion. “But people don’t want to hear what we’re saying, namely: this virus is going to mutate.”

The new genetic deletion changes the spike protein on the surface of the coronavirus that it needs to infect human cells. Variants of the virus with this deletion appeared independently in Thailand and Germany in early 2020 and were distributed in Denmark and England in August.

Scientists initially thought the new coronavirus was stable and unlikely to escape a vaccine-induced immune response, said Dr. Deepti Gurdasani, a clinical epidemiologist at Queen Mary University in London.

“But in the last few months it has become very clear that mutations can occur,” she said. “As selection pressure increases with mass vaccination, these mutants will likely appear more frequently.”

Several recent publications have shown that the coronavirus can evolve to avoid detection by a single monoclonal antibody, a cocktail of two antibodies, or even a convalescent serum given to a particular individual.

Fortunately, the body’s entire immune system is a much more formidable enemy.

The Pfizer-BioNTech and Moderna vaccines induce an immune response only to the spike protein that the coronavirus carries on its surface. But every infected person produces a large, unique and complex repertoire of antibodies against this protein.

“The fact is you have a thousand great guns aimed at the virus,” said Kartik Chandran, a virologist at Albert Einstein College of Medicine in New York. “No matter how the virus turns and weaves, it is not that easy to find a genetic solution that can really fight all of these different antibody specificities, let alone the other arms of the immune response.”

In short, it will be very difficult for the coronavirus to escape the body’s defenses, despite the many variations it can take.

To escape immunity, a virus has to accumulate a series of mutations that allow the pathogen to undermine the effectiveness of the body’s defenses. Some viruses, such as influenza, accumulate these changes relatively quickly. But others, like the measles virus, hardly collect changes.

Even the influenza virus takes five to seven years to collect enough mutations to completely evade immune recognition, noted Dr. Bloom. His lab released a new report on Friday showing that cold coronaviruses also evolve to evade immune recognition – but over many years.

The extent of the infections in this pandemic can quickly lead to diversity in the new coronavirus. Still, a vast majority of people around the world have yet to become infected, and that has given scientists hope.

“It would be a little surprising to me if we saw active selection for immune escape,” said Emma Hodcroft, a molecular epidemiologist at the University of Bern in Switzerland.

“In a population that is still largely naive, the virus just doesn’t have to do that yet,” she said. “But it’s something we want to look out for in the long term, especially when we get more people vaccinated.”

Immunizing about 60 percent of the population within a year and reducing the number of cases along the way can help minimize the chance of a significant mutation in the virus, said Dr. Hodcroft.

Still, scientists need to closely track the developing virus to identify mutations that could give it an advantage over vaccines.

Scientists routinely monitor mutations in flu viruses to update vaccines and should do the same for the coronavirus, said Trevor Bedford, evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.

“You can imagine that there is a similar process for the flu vaccine where you swap out these variants and everyone gets their annual covid shot,” he said. “I think that will be necessary in general.”

The good news is that the technology used in Pfizer-BioNTech and Moderna’s vaccines is much easier to customize and update than traditional vaccines. The new vaccines also generate a massive immune response so the coronavirus may need many mutations over the years before vaccines need to be tweaked, said Dr. Bedford.

In the meantime, the Centers for Disease Control and Prevention and other government agencies should set up a national system to link viral sequence databases to on-site data – for example, whether an infection has occurred despite vaccination.

“These are useful suggestions for scientists and governments to put systems in place – now before we could need them, especially when we start vaccinating people,” said Dr. Hodcroft. “But the public shouldn’t necessarily panic.”

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