A SARS-CoV-2 variant that came to researchers’ attention last April and quickly came to dominate the COVID-19 pandemic has been evaluated in the laboratory, where experiments have been performed showing that an engineered version of the new variant infects human cells about three to six times more effectively than does the previously dominant variant. The new variant could also be more transmissible, but this possibility has yet to be confirmed. What does seem clear, however, is that the new variant does not cause more severe disease.
The laboratory results were detailed in an article that appeared in the journal Cell, in an article titled, “Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus.” Besides addressing the question of infectivity, the article presents geographic information about the rise of the new variant, G614, and the relative decline of the previously dominant variant, D614, across the globe.
This figure shows the running weekly average counts of sampled SARS-CoV-2 sequences exhibiting the D variant (orange) and G variant (blue) in different continents between January 12 and May 12. [Korber et al. / Cell]“Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional, and municipal,” the article’s authors wrote. “The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage.”
The article’s authors also emphasized that the G614 variant has a small but effective change in its “Spike” protein, which the virus uses to enter human cells.
“The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern, said Bette Korber, the study’s lead author and a theoretical biologist at Los Alamos National Laboratory. “All over the world, even when local epidemics had many cases of the original form circulating, soon after the D614G variant was introduced into a region it became the prevalent form.”
To confirm this observation, two of the study’s co-authors—Erica Ollmann Saphire, PhD, a professor at the La Jolla Institute, and David Montefiori, PhD, a professor at Duke University—led the experiments showing that the D614G change increases the virus’s infectivity in the laboratory. To provide additional confirmation, the paper presents more extensive sequence and clinical data and improved statistical models.
“We found that the G614 variant grows to higher titer as pseudotyped virions,” the article’s authors noted. “In infected individuals, G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity.”
The SARS-CoV-2 virus has a low mutation rate overall (much lower than the viruses that cause influenza and HIV-AIDS). The D614G variant appears as part of a set of four linked mutations that appear to have arisen once and then moved together around the world as a consistent set of variations.
“It’s remarkable to me,” commented Will Fischer, PhD, department member, theoretical division, at Los Alamos National Laboratory and one of the study’s co-authors, “both that this increase in infectivity was detected by careful observation of sequence data alone, and that our experimental colleagues could confirm it with live virus in such a short time.”
Korber noted, “These findings suggest that the newer form of the virus may be even more readily transmitted than the original form—whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing.”
Saphire says the novel coronavirus could be successful precisely because many patients do only get a mild version, or no symptoms at all.
“The virus doesn’t ‘want’ to be more lethal. It ‘wants’ to be more transmissible,” Saphire explained. “A virus ‘wants’ you to help it spread copies of itself. It ‘wants’ you to go to work and school and social gatherings and transmit it to new hosts. Of course, a virus is inanimate—it doesn’t ‘want’ anything. But a surviving virus is one that disseminates further and more efficiently. A virus that kills its host rapidly doesn’t go as far—think of cases of Ebola. A virus that lets its host go about their business will disseminate better—like with the common cold.”
So, while the G mutation doesn’t make cases more severe, a different mutation might. “We’ll be keeping an eye on it,” said Saphire.
“[Our] findings,” the authors of the Cell article concluded, “illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.”
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