Early Coronavirus Mutation Made It Tougher to Cease, Proof Suggests

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

However, a mutation at the start of the pandemic made a difference. Several new findings suggest that the virus is easier to spread from person to person and the pandemic is harder to stop.

The mutation known as 614G was first discovered in east China in January and then quickly spread across Europe and New York City. Within a few months, the variant took over much of the world and supplanted other variants.

Scientists have been discussing why for months. Researchers at Los Alamos National Laboratory argued in May that the variant likely developed the ability to infect people more efficiently. Many were skeptical, arguing that the variant might just have gotten lucky and was more likely to occur randomly in major epidemics like northern Italy that sparked outbreaks elsewhere.

However, a plethora of new research – including detailed genetic analysis of outbreaks and laboratory work on hamsters and human lung tissue – has supported the view that the mutated virus did indeed have a distinct advantage and infected people more easily than the original variant found in Wuhan, China.

There’s no evidence that coronavirus with the 614G mutation causes more serious symptoms, kills more people, or makes vaccines difficult to develop. The results also don’t change the reality that places that have been quickly and aggressively imposed bans and promoted measures such as social distancing and masks fared far better than those that didn’t.

But the subtle change in the virus’s genome appears to have had a big ripple effect, said David Engelthaler, a geneticist at the Translational Genomics Research Institute in Arizona. “When all is said and done, it could be that this mutation caused 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. Angel thaler. The original variant, discovered in Wuhan, China, in late 2019, is already highly contagious, he said. But the mutation appears to have spread the pandemic further and faster than it would have without it.

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

Laboratory studies have shown that mutations of the Ebola virus that spread in West Africa from 2013 onwards increased the infectivity in tissue culture. However, this conclusion did not lead to increased transmission in animal laboratory studies. And some experts said the effect of the 614G mutation could be modest compared to other factors, like the social distancing rate.

But the new insights from research groups in the UK and the United States have changed the minds of many scientists who were initially skeptical.

One study found that outbreaks in communities in the UK increased faster when planted with the 614G variant than when planted by Wuhan’s ancestors. Another reported that hamsters got infected faster when exposed to the variant. And in a third case, the variant infected human bronchial and nasal tissue in a cell culture dish far more efficiently than its ancestor.

Trevor Bedford, associate professor at the Fred Hutchinson Cancer Research Center and the University of Washington, said he was won over by the collection of evidence from various research areas.

“My belief comes from seeing the same thing over and over,” said Dr. Bedford. “I think at this point that it’s real.”

Dr. Bedford and other scientists were impressed with the new work, but said it was still unclear whether an inherent benefit was the main reason behind the variant’s global dominance.

Kristian Andersen, a geneticist at Scripps Research, La Jolla, said the research showed that the variant is more transmissible, but he believes the difference is subtle.

Still, Dr. Andersen that the variant’s higher transferability could explain why some countries that originally successfully contained the virus later became susceptible to it. The virus may be “harder to contain than the first time,” he said.

“What you’ve done before may not be enough to control it,” said Dr. Andersen. “Don’t necessarily expect the enemy from two months ago to be the enemy you will have next time.”

Around the world, the advent of the 614G has sparked both serious academic debate and largely political evasion of blame. Government officials in Vietnam and Thailand, who did well to contain the ancestral tribe despite the influx of Chinese visitors earlier in the year, have suggested that the later outbreaks were partly due to the 614G virus.

Thailand has kept both variants of the virus under control over the past year by strictly quarantining returnees, banning foreign tourists, masks and other measures, said Thira Woratanarat, an associate professor at the medical school at Chulalongkorn University in Bangkok. Still, he said, resurrections in the region are worrying.

“We saw several countries like Vietnam, South Korea and Japan that seemed to have it under control,” said Dr. Thira. “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 outbreak quickly spread to 10 cities and provinces. In Singapore, he said, the mutated virus spread in overcrowded dormitories for migrant workers.

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

However, other researchers said a lack of proper containment measures, not the mutation, is largely responsible for resurgent outbreaks.

“The reason is that people don’t have enough measures,” said Kari Stefansson, founder and CEO of deCODE Genetics, a leading genome analysis company based in Iceland. “It seems extremely bad policy to attribute the inadequacies to the virus. They should pick someone their size, not this tiny virus. “

In one of the new studies, a British research team had an advantage that no one else shared: they were able to access the world’s largest national database of coronavirus genome sequences. The researchers gathered new evidence that the variant was at least adopted in the UK because it is actually spreading faster.

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

The data collected by the Covid-19 Genomics UK Consortium enabled the team to observe the growth of infected clusters as a kind of horse race. Did clusters of 614G infections grow next to each other faster than infections with the ancestral variant?

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

“This is exactly the type of analysis that needed to be done and it offers more support for G being 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 and compared the 614G variant to the ancestral version. In one case, the team found that 614G virus was more infectious in samples of human bronchial and nasal tissue, the most likely source of virus that can be passed on to others.

Another study published in Science found that the variant was more easily transmitted in hamsters when infected animals were only a few inches apart. Scientists view animal testing as a critical step in testing whether a mutation that makes viruses in a laboratory dish more contagious will do so in a living population.

Dr. Baric’s team placed an infected hamster in a cage next to the cage of an uninfected one. The cages were a few centimeters apart so that the animals could not touch. Any transmission can only occur through the air, in droplets, or in aerosols.

After two days, five out of eight hamsters had infected their pair with the 614G variant. None of those with the ancestral virus had done this.

“If you put all the data together, everything is consistent with a system that increases infectivity and communicability,” said Dr. Baric.

The virus will keep changing, and while most of those changes are just typo, some could be more meaningful, said Dr. Angel thaler. “There will be the possibility of additional changes that will change the nature of the pandemic,” he said.

Dr. Engelthaler previously said he saw strong evidence of such changes in his own unpublished data, which tracks the spread of different variants in Arizona.

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

Muktita Suhartono contributed to the coverage.

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