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Seattle researchers zero in on COVID virus mutation that could be driving spread of new variants

Geekwire logo Geekwire 3/4/2021 Lisa Stiffler
a hand holding a plastic bag: Veronika Tchesnokova, a researcher at the University of Washington School of Medicine and the Seattle startup ID Genomics, is the first author of a new study on a worrisome mutation in the COVID virus. (UW Photo) © Provided by Geekwire Veronika Tchesnokova, a researcher at the University of Washington School of Medicine and the Seattle startup ID Genomics, is the first author of a new study on a worrisome mutation in the COVID virus. (UW Photo)

A team of researchers from Seattle is raising concerns about a mutation in the COVID-19 virus that’s infecting growing numbers of people in Washington state and beyond.

The L452R mutation affects the spike protein that studs the virus, leading to its crown or corona shape. The spike is also responsible for sticking to and invading human cells, causing infections. Changes in the spike can potentially lead to a more potent virus.

The mutation is present in what’s called the California variant, also known as B.1.427/B.1.429, and another less common California lineage that had the distinction of infecting gorillas at the San Diego Zoo Safari Park — the first known case of COVID in great apes. In a search of public databases, the Seattle scientists found the mutation in at least half a dozen separate lineages around the world.

“It’s something that immediately we need to be jumping on,” said Dr. Evgeni Sokurenko, a professor of microbiology at the University of Washington School of Medicine.

Mutations — changes in the genetic code that can alter how the virus behaves — occur frequently in RNA viruses, including the SARS-CoV-2 virus that causes COVID. Mutations can cause a variety of effects, some that impact the pandemic and others that don’t. A consistent set of mutations seen over and over again that cause problems are tracked as variants.

a man standing in front of a computer: Dr. Evgeni Sokurenko, a professor of microbiology at the University of Washington School of Medicine. (UW Photo) © Provided by Geekwire Dr. Evgeni Sokurenko, a professor of microbiology at the University of Washington School of Medicine. (UW Photo)

Sokurenko, the senior author of a new, not yet peer-reviewed study, suggests that this specific, small mutation could be the secret to these variants’ success in causing increasing numbers of infections.

“The emergence of these variants, it adds such a big unknown to our future,” said Dr. Cindy Liu, an associate professor in the Milken Institute School of Public Health at George Washington University. “It’s an incredibly important issue in terms of how we respond to it.”

The California variants are currently classified as “variants under investigation” by the U.S. Centers for Disease Control and Prevention. The most serious mutants are dubbed “variants of concern.” That designation is assigned when the variant is shown to either be more easily transmitted, cause people to become sicker, render the vaccines less effective or any combination of these effects.

There is evidence suggesting the California variants could carry all three of these negative effects. But the research at this point is limited, and experts differ in their opinions of the relative threat.

California variants increasingly prevalent

Dr. Charles Chiu, a virologist at the University of California, San Francisco, was one of the first to identify the most common California variant. His research indicates it’s more infectious, but he recently told the New York Times that it was unclear how vaccines will perform against it.

Variants of concern include the United Kingdom variant, or B.1.17; the South African or B.1.351; and a variant from Brazil. The UK and South African variants were recently identified in Washington state. The state is reporting officially only on the variants of concern.

The California variant first began infecting people in California in July, but in November the number of COVID cases caused by L452R mutants began increasing dramatically and they’ve continued to grow. Washington state has many fewer infections from these variants, but the number is rising in the state, as well.

The website Outbreak.info, a project tracking variants that’s run by labs at Scripps Research, has plotted the increases. The site estimates that 35% of COVID cases in California are from viruses containing the L452R mutation, and 15% of Washington state cases include it. The percentages are only rough estimates, however, and draw from available data as opposed to data selected to be precisely representative of prevalence.

An Outbreak project scientist warned against making strong conclusions about the impact of the mutation, such as whether it drove California’s case outbreak in December and January.

“Is the variant causing the surge, or is it because of the surge that the variant’s increasing?” said Karthik Gangavarapu, a graduate student in the Scripps Department of Immunology and Microbiology.

At the same time, Gangavarapu agreed that the California variant could wind up a variant of concern.

Role of vaccines

It’s unclear how the California variant behaves against existing COVID vaccines, but the shots can be modified to better match them, experts say. The mRNA vaccines like those produced by Moderna and Pfizer are more amenable to updates than traditional vaccines, and Moderna is ready to start testing a version targeting the South African variant.

Deborah Fuller, a professor of microbiology in the UW’s Department of Medicine who was not part of the Seattle study, said that for those who have had a COVID infection or vaccination, a booster shot including the new variants should goose a person’s immune response much like an annual flu shot does.

“That is the thinking,” she said, “that it’s going to work kind of like influenza.”

Given that COVID is unlikely to be eliminated any time soon, researchers emphasized the need to stay focused on treatments for COVID patients, as well. It could make sense to tailor the approach depending on which form of the virus infects someone.

A collection of dipsticks used to detect different mutations in the virus that causes COVID-19. The Sokurenko lab and researchers at a UW startup called ID Genomics and IEH Laboratories and Consulting Group are working to develop a rapid detection test for screening for mutants. (UW Photo) © Provided by Geekwire A collection of dipsticks used to detect different mutations in the virus that causes COVID-19. The Sokurenko lab and researchers at a UW startup called ID Genomics and IEH Laboratories and Consulting Group are working to develop a rapid detection test for screening for mutants. (UW Photo)

Sokurenko’s co-authors on the research paper include colleagues at the UW; Kaiser Permanente Washington; the nonprofit Antibiotic Resistance Monitoring, Analysis, and Diagnostic Alliance (ARMADA); and two biotech companies: a UW startup called ID Genomics, and IEH Laboratories and Consulting Group.

Sokurenko, who co-founded ID Genomics, is working with the startup and IEH Laboratories to develop a rapid and simple test for identifying the different virus mutations. The tests work something like a pregnancy test, showing bands of color when certain mutations are present, and can take two hours or less to generate results directly from the sample — a much quicker and likely cheaper alternative to sequencing the entire viral genome or genome regions.

The researchers are applying for a grant from the National Institutes of Health to ramp up development and commercialization of the tests.

On Wednesday, the Washington Department of Health announced that it was boosting its ability to search for COVID variants with faster sequencing equipment that uses nano-technology being deployed at a public health lab in Shoreline. The state is currently sequencing 2% of COVID-positive cases and hopes to increase that rate to 5%.

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