Coronavirus mutation spreads worldwide

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The fact that viruses mutate over time is not unusual, as is the case with the coronavirus Sars-CoV-2. But as it now turns out, a mutant of the new virus appears to be particularly successful. It has spread almost worldwide during the Corona pandemic and has become the dominant and most common form of Sars-CoV-2, as analysis of thousands of genome sequences of various virus isolates shows.

Complementary laboratory tests have shown that this mutated G614 variant has increased infectivity – it can infect human cells more effectively and multiply three to six times more than the original form. However, the severity of the Covid-19 courses does not seem to affect this.

All viruses mutate over time. This is because copying errors can occur again and again when they multiply in the host cells, which are then passed on by the viral “descendants”. Typically, such mutations are particularly common in RNA viruses because they cannot use the DNA correction mechanisms of host cells. It is therefore no coincidence that a particularly large number of newly occurring and newly adapted pathogens belong to the RNA viruses. The coronavirus Sars-CoV-2 also changes over time, albeit comparatively slowly. Scientists have been tracking its development since the beginning of the pandemic by repeatedly isolating virus samples from patients and analyzing their genetic material. The giSAID central database now collects tens of thousands of such genome sequences for Sars-CoV-2. By comparing these viral RNA sequences, it is possible to determine where and how much the virus has mutated – but also how it has spread around the world.

Spread around the world

As early as the end of April 2020, a team of researchers led by Bette Korber of the Los Alamos National Laboratory reported on a mutation of Sars-CoV-2 that spread particularly strongly in an as yet unexamined paper – a so-called preprint. “Whenever this mutation reached a population, its frequency increased rapidly, and in many cases it became the dominant form in just a few weeks,” the researchers report. This mutation causes the amino acid asparagine to be exchanged for glycine at one point of the viral spike protein, the surface protein with which the coronavirus binds to human cells. Back in April, the researchers found that this G614 variant of Sars-CoV-2 spreads more than the original D614 form by comparing genes. More virus sequences are now available and Korber and her team have increased their sequence comparisons from 6000 to 30,000.

The new results confirm the rapid spread of the mutant coronavirus variant. “The Sars-CoV-2 variant with the amino acid change has become the most common form in the global pandemic,” the researchers report. “Even where the original D614 form was well established before the creation of G614, a change has taken place.” Before March 1, 2020, the mutant form was found in only about ten percent of the virus sequences registered worldwide, by the end of March its share had already grown to 67 percent, and by mid-May, the G614 form accounted for 78 percent of all sars-CoV-2 isolates sequenced worldwide. In further analyses, the scientists investigated when and where the genetic mutations underlying this amino acid change first occurred. “The earliest examples of parts of the four mutations of the genome type were detected in China and Germany at the end of January,” Said Korber and her colleagues. “They already had three of the four RNA mutations that define this type.” The first virus carrying all four mutations was detected in Italy on 20 February and spread throughout Europe within days.

Faster propagation

This rapid triumph of the new virus mutant raises the question of why it is so successful. “We could see in our first study that the G614 variant became the dominant form, but we couldn’t determine which of the possible causes is behind this increase in fitness,” Says Korber. She and her team have therefore carried out additional analyses and experiments in collaboration with other research groups. On the one hand, they evaluated the clinical data of 999 Covid-19 patients who had been treated at a hospital in Sheffield, UK. It was found that patients infected with the G614 mutant of Sars-CoV-2 had on average a higher viral load in the body. “However, we did not find a significant correlation between D614G status and the severity of the disease and the course,” the scientists stress. In addition, the mutant virus variant appears to be fought just as effectively by neutralizing antibodies as the original form, as laboratory tests with antibodies from the serum of recovered patients showed.

On the other hand, tests for infectivity showed a clear advantage for the mutant virus. A team led by Erica Ollmann Saphire of the La Jolla Institute for Immunology and David Montefiori of Duke University had infected cell cultures in the lab with mutated and non-mutated forms of Sars-CoV-2. “Virus particles containing the G-shape of the Spike protein were three to six times more infectious,” the researchers report. The G614 variant therefore seems to find it easier to enter human cells and multiply in them.

This could explain the higher viral load of the affected patients and the rapid spread of this mutant. “The in vitro results support clinical observations, both suggesting that viruses with the G614 mutation may multiply more strongly in human cells,” Nathan Grubaugh of Yale University said in an accompanying commentary. ‘But what we can’t say yet is whether this mutant is also easier to transfer and exacerbates the pandemic.’ According to the virologist, however, it is unlikely that this mutation of Sars-CoV-2 will make the individual course of the disease worse or that containment measures will have to be changed as a result.