Early mutation of coronavirus made pandemic harder to stop, evidence shows



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As the coronavirus swept the world, it detected random alterations in its genetic sequence. Like meaningless typos in a script, most of these mutations made no difference in the behavior of the virus.

But a mutation early in the pandemic made a difference, many new findings suggest, helping the virus to spread more easily from person to person and making the pandemic more difficult to stop.

The mutation, known as 614G, was first spotted in eastern China in January, then quickly spread across Europe and New York. Within months, the variant has taken over much of the world, replacing other variants.

For months, scientists have been puzzling over why. Researchers at the Los Alamos National Laboratory argued in May that the variant likely developed the ability to infect people more effectively. Many were skeptical, saying the variant may have been lucky, appearing more often by chance in large outbreaks, like those in northern Italy, which have caused outbreaks elsewhere.

But a host of new research – including extensive genetic analysis of outbreaks and lab work with hamsters and human lung tissue – has supported the idea that the mutated virus actually has a distinct advantage, infecting people more easily. than the original variant detected in Wuhan. , China.

There is no evidence that a coronavirus with the 614G mutation causes more severe symptoms, kills more people, or complicates vaccine development. Nor does the results change the reality that lockdowns adopted quickly and aggressively and encouraged measures such as social distancing and masks fared much better than those that did not.

But the subtle change in the virus’s genome appears to have had a strong ripple effect, said David Engelthaler, a geneticist at the Institute for Translational Genomics Research in Arizona. “Ultimately, it could be that this mutation is the root cause of the pandemic,” he said.

The first outbreaks of the virus would have spread around the world even without the mutation, believe most researchers, including Dr Engelthaler. The original variant spotted in Wuhan, China in late 2019 was already very contagious, he said. But the mutation appears to have made the pandemic spread further and faster than it would have without it.

Scientists are particularly careful in this area of ​​virology.

Laboratory studies have shown that mutations in the Ebola virus, which spread in West Africa from 2013, increased the infectivity of tissue cultures. But this finding has not translated into increased transmission in laboratory studies with animals. And some experts have said that the effect of the 614G mutation may be modest compared to other factors, such as social distancing rates.

But the new evidence, coming from research groups in the UK and US, has changed the minds of many scientists who were initially skeptical.

One study found that outbreaks in communities across the UK grew faster when seeded by the 614G variant than when seeded by its ancestor in Wuhan. Another reported that hamsters became infected more quickly when exposed to the variant. And in a third, the variant infected human bronchial and nasal tissue in a cell culture dish much more efficiently than its ancestor.

Trevor Bedford, associate professor at the Fred Hutchinson Cancer Research Center and the University of Washington, said collecting results from different lines of research convinced him.

“My being convinced has just seen the same thing over and over,” Dr Bedford said. “I think at this point it’s real.”

While impressed with the new work, Dr Bedford and other scientists said it was still not clear whether an inherent advantage was the main reason for the variant’s global dominance.

Kristian Andersen, geneticist at Scripps Research, La Jolla, said research has shown the variant to be more heritable, but he thinks the difference is subtle.

Despite this, Dr Andersen said the higher transmissibility of the variant might help explain why some countries that initially succeeded in containing the virus later became there. The virus may have been “more difficult to contain than the first time,” he said.

“What you were doing may not be quite enough to control it,” Dr Andersen said. “Don’t necessarily expect the enemy of two months ago to be the enemy you have next time.”

Around the world, the emergence of 614G has generated both serious scientific debate and largely political evasion. Government officials from Vietnam and Thailand, which were successful in containing the ancestral strain despite an influx of Chinese visitors earlier this year, have suggested that the latest outbreaks may have been in part the result of the 614G virus.

Thailand has kept both variants of the virus under control over the past year through strict quarantine of returnees, a ban on foreign tourists, masks and other measures, said Thira Woratanarat, associate professor at Bangkok’s Chulalongkorn University Faculty of Medicine. Yet, he said, the resurgences in the region are worrying.

“We saw several countries, like Vietnam, South Korea and Japan, that seemed to have it under control,” Dr Thira said. “But then there was a second wave.”

In Vietnam, he said, the virus with the 614G mutation was first confirmed in the central coastal city of Danang after about 100 days with no reported cases of local transmission. An epidemic quickly spread to 10 cities and provinces. In Singapore, he said, the mutated virus has spread to crowded dormitories for migrant workers.

“When the mutated virus lives in large groups, it spreads faster and makes it much more difficult to control,” he said.

But other researchers have said the lack of proper containment measures, not the mutation, is largely to blame for the resurgence of outbreaks.

“The reason this is spreading is that people don’t have enough measures in place,” said Kari Stefansson, founder and CEO of deCODE Genetics, a leading genome analysis company based in Iceland. “It seems like an extremely poor policy to blame the deficiencies of the virus. They should be going after someone their size, not this little virus. “

In one of the new studies, a British team of researchers did not have one advantage shared by no one else: they were able to draw on the world’s largest national database of coronavirus genome sequences. Researchers have gathered new evidence that, at least in the UK, the variant has taken over as it is indeed spreading faster.

“When we look at the clusters, variant G grows faster,” said Erik M. Volz, a researcher at the Medical Research Council Center for Global Infectious Disease Analysis at Imperial College London and head of the study.

Data collected by the Covid-19 Genomics UK Consortium allowed the team to observe the growth of infected clusters like a kind of horse race. Side by side, did the 614G infection clusters grow faster than the infections involving the ancestral variant?

The 614G variant clearly won the race, according to the analysis. The precise rate remains uncertain, but the most likely value gives 614G an advantage of around 20% in its exponential growth rate.

“This is exactly the kind of analysis that needed to be done, and it gives more support for G to be more transmissible” than the ancestral virus, said one of the researchers, Katharina V. Koelle, associate professor of biology at Emory University.

In a separate series of studies, a team led by Ralph Baric of the University of North Carolina tested live viruses, comparing the 614G variant to the ancestral version. In one, the team found that the 614G viruses were more infectious in human bronchial and nasal tissue samples, the most likely source of the virus to pass on to others.

Another study, published in Science, found that the variant was more easily transmitted in hamsters when infected animals were within inches of each other. Scientists consider animal testing to be a critical step in testing whether a mutation that makes viruses more infectious in a lab box also does so in a living population.

Dr Baric’s team placed an infected hamster in a cage, next to the cage of an uninfected hamster; the cages were spaced several inches apart, so the animals could not touch each other. All transmission can only occur through air, in the form of droplets or aerosols.

After two days, five of the eight hamsters with the 614G variant had infected her pair. None of those who had the ancestral virus had.

“When you take all of the data together, everything is compatible with a system that increases infectivity and transmissibility,” said Dr Baric.

The virus will continue to change. and while most of these changes will be simple typos, some can be more significant, Dr. Engelthaler said. “There will be the possibility of further modifications that will change the nature of the pandemic,” he said.

Already, Dr. Engelthaler said, he has seen strong indications of such alterations in his own unpublished data tracking the spread of different variants in Arizona.

“We have to listen to what the virus is telling us,” he said.

Muktita Suhartono contributed reporting.

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