Preprint findings outline the woes of SARS-CoV-2 viral mutations

Results from a preprint study identified seven Covid-19 variants that seem to have originated in the United States—and it’s possible these mutant strains are even more contagious, the study authors warned.

In their study, which was published in MedRxiv and is not yet peer-reviewed, Jeremy P. Kamil, PhD, of the Louisiana State University Health Sciences Center in Shreveport, Louisiana, and colleagues discovered that all seven variants carry the same mutation to amino acid position 677—a convergent adaptation that may signal an evolutionary advantage for these strains. And, while it is not clear yet whether this particular mutation makes these strains more contagious, the study authors have their suspicions.

“This stretch of spike is important because of its proximity to a region key for virulence,” study coauthor Vaughn Cooper, PhD, director of the Center for Evolutionary Biology and Medicine at the University of Pittsburgh School of Medicine in Pittsburgh, told CNN. “…We actually think these mutations are relatively rare (compared to other types of mutation), but they are disproportionately selected when they occur.”

“There’s clearly something going on with this mutation,” Kamil said, according to the New York Times. “…I think there’s a clear signature of an evolutionary benefit.”

For their analysis, two independent SARS-CoV-2 genomic surveillance programs — one from Louisiana State University Health Sciences Center and one from New Mexico Health Sciences in Albuquerque — monitored data from the Global Initiative on Sharing Avian Influenza Data (GISAID) database for the latter half of 2020. Kamil and colleagues found that SARS-CoV-2 samples carrying an S:Q677P mutation became much more prevalent during this time, already accounting for “over 2,327 of the 102,462 genomes deposited to GISAID from the USA,” despite only beginning to appear around mid-August 2020, they explained.

The study authors named the seven variants after birds to help make them easier to identify.

The largest of the 677 variant sub-lineages — accounting for 754 sequences — was dubbed “Robin 1” and was first identified on Aug. 17 of last year, they explained. Thus far, Robin 1 has cropped up in over 30 states, but it is most prevalent in the Midwest. A second variant, which first appeared on Oct. 6, originated in Alabama and was labeled “Robin 2” due to its similarity to Robin 1. A third variant, called “Pelican,” first appeared in Oregon and has since been identified in 12 other states, as well as Australia, Denmark, Switzerland, and India.

“The remaining Q677H sub-lineages each contain around 100 or fewer sequences, and are named: Yellowhammer, detected mostly in the southeast U.S.; Bluebird, mostly in the northeast United States; Quail, mainly in the Southwest and Northeast; and Mockingbird, mainly in the South-central and East coast states,” Kamil and colleagues wrote.

“Although it is too early to predict whether any particular S:677 polymorphic lineages will persist… the recurrent parallelism affecting S:677 suggests that this position will continue to surface in variants that show signs of increased transmissibility or fitness,” they added. “It will thus be critical to not only to continue genomic surveillance of SARS-CoV-2 to monitor the prevalence of such variants over time, but also to formally define any biological characteristics of these polymorphisms in cell culture and small animal model systems.”

U.K. Government Reports Higher Mortality with B.1.1.7 Variant

U.K. scientists released an assessment ahead of peer-review late last week that suggests that the B.1.1.7 Covid-19 variant — which emerged in the U.K. in September 2020 and which the CDC projected would be the primary Covid-19 strain in the U.S. by March of this year — may be between 30% and 70% deadlier than the original SARS-CoV-2 virus.

This report, which compiled data and studies from multiple institutions across the U.K., backed up concerns of increased lethality that were sparked by a January report from the U.K.’s New and Emerging Respiratory Threats Advisory Group.

Though it is not entirely clear why this variant carries an elevated death rate, evidence suggests that those infected may have higher viral loads, leading to higher transmissibility and more severe disease. However, the researchers added, “it should be noted that the absolute risk of death per infection remains low.”

The researchers also pointed out limitations to their assessment; for example, the majority of the included analyses were limited to community testing data, the number of deaths included in some datasets was low, and nursing home status may be poorly identified.

“I think these results are possibly genuine, although there are still several limitations and we need to understand what causes it,” Muge Cevik, MD, MSc, MRCP, of the University of St. Andrews in Scotland, scientific advisor to the British government, told the Times. She noted that the increased severity might be explained by disproportionate spread among frailer people, such as residents in nursing homes and other long-term care facilities, as a result of the variant’s heightened transmissibility.

’Breakthrough’ Infections?

Mere days after the CDC released updated guidance stating that fully vaccinated individuals do not need to quarantine after Covid-19 exposure, Covid-19 cases were reported among individuals who had already received their second vaccine dose.

As of Feb. 13, five of these “breakthrough cases” were reported, four in Oregon and one in North Carolina — and, fortunately, all five cases were either mild or asymptomatic and did not require hospitalization, public health officials reported.

In a series of tweets, Oregon Health Authority State Health Officer Dean Sidelinger noted that the occurrence of breakthrough cases is not unexpected, adding that, “Based on what we know about vaccines for other diseases and early data from clinical trials, experts believe that getting a Covid-19 vaccine may also help keep you from getting seriously ill even if you do get the virus.

“What all this means is that we can expect to see more breakthrough cases,” he added. “Getting as many Oregonians as possible vaccinated remains a critical objective to ending the pandemic.”

Sidelinger concluded by noting that citizens should continue to take steps to prevent viral transmission while the state continues to get people vaccinated — in particular, he pointed to the CDC’s recent report in Morbidity and Mortality Weekly Report that found double masking and tightly fitted masks to be more effective in reducing Covid-19 infection.

John McKenna, Associate Editor, BreakingMED™

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