Mutations Cause COVID-19’s Second Wave

A new study confirms that the SARS-CoV-2 coronavirus has mutated in a way that has enabled it to spread quickly around the world.

The new strain of coronavirus, called D614G, emerged in Europe and has become the most common in the world, according to researchers at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison.

These researchers believe the D614G strain of coronavirus dominates because it increases the spike protein's ability to open cells for the virus to enter. 

This study published in Science on November 12, 2020, shows the D614G strain replicates 10-times faster and is more transmissible than the initial SARS-CoV-2 that spread globally during early 2020.

"The D614G virus outcompetes and outgrows the ancestral strain by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission," said Ralph Baric, professor of epidemiology at the UNC-Chapel Hill Gillings School of Global Public Health and professor of microbiology and immunology at the UNC School of Medicine, in a related press release.

The D614G mutation causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus's vulnerable core.

"The original spike protein had a 'D' at this position, and it was replaced by a 'G,'” added Yoshihiro Kawaoka. "Several papers had already described that this mutation makes the protein more functional and more efficient at getting into cells."

Using reverse genetics, Baric's team replicated a matched pair of mutant SARS-CoV-2 viruses that encoded D or G at position 614 and compared basic property analysis using cell lines, primary human respiratory cells, and mouse and hamster cells.

The University of Wisconsin-Madison team, which ran the hamster experiments, performed replication and airborne transmission studies with both the original virus and the mutated versions.

Hamsters were inoculated with one virus or the other. The next day, eight uninfected hamsters were placed into cages next to infected hamsters. There was a divider between them so they could not touch, but air could pass between the cages.

The researchers began looking for replication of the virus in the uninfected animals on day two. 

Both viruses passed between animals via airborne transmission, but the timing was different.

With the mutant virus, the researchers saw transmission to six out of eight hamsters within two days, and to all the hamsters by day four. With the original virus, they saw no transmission on day two, though all of the exposed animals were infected by day four.

"We saw that the mutant virus transmits better airborne than the [original] virus, which may explain why this virus dominated in humans," Kawaoka said.

The researchers also examined the pathology of the two coronavirus strains. Once hamsters were infected, they presented essentially the same viral load and symptoms. (The hamsters with the mutated strain lost slightly more weight while sick.) This suggests that while the mutant virus is much better at infecting hosts, it doesn't cause significantly worse illness.

Researchers caution that the pathology results may not hold true in human studies.

"SARS-CoV-2 is an entirely new human pathogen and its evolution in human populations is hard to predict," Baric said. "New variants are continually emerging, like the recently discovered mink SARS-CoV-2 cluster 5 variant in Denmark that also encodes D614G.” 

"To maximally protect public health, we must continue to track and understand the consequences of these new mutations on disease severity, transmission, host range, and vulnerability to vaccine-induced immunity."

This study concluded by saying ‘the relationship between increased transmission and virulence remains complex and could be impacted by age, sex, and other comorbidities, and it is unclear whether the minimum infectious dose may be lower for D614G in humans.’ 

‘It is clearly important to monitor and identify the emergence of new variants of SARS-CoV-2 with increased transmission and pathogenesis and/or altered antigenicity, especially as levels of human herd immunity and active interventions alter the selective forces that operate on the genome.’

This work was supported by grants from the U.S. National Institutes of Health and others. No industry conflicts of interest were disclosed by these researchers.

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