A new study by one of the top Chinese scientists has revealed that the ability of the new coronavirus to mutate has been largely underestimated and different strains may explain the different impacts of the disease in different parts of the world.
Professor Li Lanjuan and colleagues from Zhejiang University found many previously unreported mutations in a small group of patients.
These mutations included changes so rare that scientists never thought they could happen.
They also confirmed for the first time with laboratory evidence that some mutations could create more lethal strains than others.
“Sars-CoV-2 has acquired mutations capable of substantially modifying its pathogenicity,” wrote Li and his collaborators in an unpaired article published on Sunday on the medRxiv.org preprint service.
Li’s study provided the first tangible evidence that the mutation could affect the severity of the virus causing disease or damage to its host.
Li has taken an unusual approach to investigating the mutation of the virus. She analyzed the viral strains isolated from 11 randomly selected Covid-19 patients in Hangzhou in eastern Zhejiang province, then tested the effectiveness with which they could infect and kill the cells.
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The deadliest mutations in Zhejiang patients had also been found in most patients across Europe, while the milder strains were the predominant varieties found in parts of the United States, such as Washington, according to their article.
A separate study found that strains from New York were imported from Europe. The death rate in New York was similar to that of many European countries, if not worse.
But the weaker mutation did not mean a lower risk for everyone, according to Li’s study. In Zhejiang, two patients in their thirties and fifties who contracted the weakest strain fell seriously ill.
Although the two eventually survived, the older patient needed treatment in an intensive care unit. This finding could shed light on the differences in regional mortality.
The rates of infection and mortality from the pandemic vary from country to country and many explanations have been offered.
Geneticists had noticed that the dominant strains in different geographic regions were inherently different. Some researchers suspected that variable death rates could be partly caused by mutations, but they had no direct evidence.
The problem was further complicated by the fact that survival rates depended on many factors, such as age, underlying health conditions or even blood type.
In hospitals, Covid-19 has been treated as a disease and patients have received the same treatment regardless of the strain they are suffering from.
Li and his colleagues suggested that defining mutations in a region could determine actions to fight the virus.
“The development of drugs and vaccines, although urgent, must take into account the impact of these accumulated mutations to avoid potential pitfalls,” they said.
Li was the first scientist to propose the Wuhan foreclosure, according to state media reports. The government followed his advice, and in late January the city of more than 11 million people was closed overnight.
The sample size in this most recent study was remarkably small. Other follow-up studies of the virus mutation generally involved hundreds, if not thousands, of strains.
Li’s team has detected more than 30 mutations. Among them, 19 mutations – about 60% – were new.
They discovered that some of these mutations could cause functional changes in the virus’s advanced protein, a unique structure on the viral envelope that allows the coronavirus to bind to human cells.
Computer simulation predicted that these mutations would increase its infectivity. To test the theory, Li and his colleagues infected cells with strains carrying different mutations.
The most aggressive strains could generate 270 times more viral load than the weakest type. These strains also killed the cells most quickly.
This is an unexpected result from fewer than a dozen patients, “indicating that the true diversity of virus strains is still largely underestimated,” Li writes in the newspaper.
The mutations were different genes from the first strain isolated in Wuhan, where the virus was first detected in late December of last year.
The coronavirus changes at an average rate of about one mutation per month. By Monday, more than 10,000 strains had been sequenced by scientists around the world, containing more than 4,300 mutations, according to the Chinese National Center for Bioinformation.
Most of these samples, however, were sequenced by a standard approach which could generate a result quickly. The genes were read only once, for example, and there was room for error.
Li’s team used a more sophisticated method known as ultra-deep sequencing. Each component of the virus’s genome has been read over 100 times, allowing researchers to see changes that could have been ignored by the conventional approach.
The researchers also discovered three consecutive changes – known as tri-nucleotide mutations – in a 60-year-old patient, which was a rare event. Usually, genes have mutated at one site at a time.
This patient spent more than 50 days in hospital, much longer than the other Covid-19 patients, and even his stool was infectious with live virus strains.
“It would be very interesting to study the functional impact of this tri-nucleotide mutation,” said Li and his colleagues in the document.
Professor Zhang Xuegong, head of the bioinformatics division of the National Information Science and Technology Laboratory at Tsinghua University, said that ultra-deep sequencing could be an effective strategy for tracking the mutation of the virus.
“It can produce useful information. “
But this approach could be much longer and more costly. It was unlikely to be applied to all samples.
“Our understanding of the virus remains quite superficial,” said Zhang.
Questions such as the origin of the virus, why it could kill healthy young people while causing no detectable symptoms in many others, left scientists scratching their heads.
“If there is a discovery that upsets the dominant perception, do not be surprised. “
– South China Morning Post