COVID-19 experts answer questions about the Omicron variant — and where it may have come from

University of Washington researcher Pavitra Roychoudhury (left) and Fred Hutch emeritus director Larry Corey. (UW and Fred Hutch Photos)

There’s not a lot known about the new COVID-19 variant Omicron, but what scientists see so far has them on alert.

The variant has dozens of mutations — some suggesting that it might spread quickly and weaken protection from vaccines and natural immunity. It is taking hold in a region in South Africa that includes Johannesburg, as cases rise, and it has been found in specimens from Europe as early as Nov. 19.

Scientists are scrambling to learn more about it. How well will vaccines work against the Omicron? Do the mutations carry a bite in the real world, or not? Is it capable of outcompeting Delta?

In the next weeks and months, answers to such questions will become clear. And Seattle researchers will have a key role in answering them.

“The scientific community has really pulled together from the first posting of this variant,” said Fred Hutch physician-scientist Larry Corey. Researchers in South Africa and Botswana released variant sequences earlier this month, soon before the World Health Organization designated it a “variant of concern” last week and dubbed it “Omicron.”

Corey is head of the COVID-19 Prevention Network, a research consortium that coordinated large clinical trials for several COVID-19 vaccines and that will be investigating Omicron. He and his colleagues have long-standing scientific partnerships with the South African Medical Research Council and other groups assessing Omicron in South Africa, originating in decades of collaborative work on HIV vaccines.

Fred Hutch researchers such as Jesse Bloom and Trevor Bedford have also taken the lead in analyzing the variant’s sequences and beginning to assess its potential danger. Bedford, who recently won a MacArthur “genius grant,” co-developed the open-source platform Nextstrain, which creates real-time views of virus “family trees.”

GeekWire spoke with Corey and with Pavitra Roychoudhury, who oversees vaccine variant testing efforts at the University of Washington School of Medicine’s virology lab, which processes a large proportion of the state’s COVID-19 tests. We asked why scientists are so concerned about Omicron, how they plan to assess the variant, and how they will know when it has reached Washington. Corey also has an idea about where it came from.

Why are scientists concerned about Omicron?

Omicron carries a large number of mutations found in other variants, as well as new ones. Some of the mutations are associated with reduced responsiveness to vaccination or immunity from natural infection, and they may also render monoclonal antibody therapy less effective. In addition, the variant has some of the same mutations that seem to have made Delta highly infectious, said Corey. “This is a human derived variant that is totally novel,” he added.

But whether the virus is as nasty as it seems to be from its sequence will need to first tested in the lab. “We have to confirm those issues functionally,” he said.

Scientists are also concerned about how the virus is acting in human populations. The Johannesburg area where the variant is increasing had a large outbreak of the Delta variant about five months ago, said Corey.

“It’s already known that many people who have picked up Omicron have had Delta infection before, because they have a registry to confirm COVID cases. So, we know it can break through Delta,” and apparently overcome natural immunity, said Corey. “That’s not 100% yet, but the data are highly suggestive.”

Corey and other virologists note that they are only starting to learn about the variant. It’s still unclear to scientists how all the mutations might interact — sometimes different mutations can even cancel each other out.

“At the end of the day, you have to think about all the mutations together and how that impacts the virus,” said Roychoudhury. “I think it just remains to be seen what the actual impact is going to be.”

What kind of lab experiments will scientists be doing to assess omicron?

In key lab experiments, researchers will investigate how well antibodies from vaccinated individuals neutralize the virus. They will be testing whole live virus and components of the virus, such as the “spike” protein, the portion of the virus targeted by the vaccine, said Corey. Answers from these lab experiments should provide scientists with a good idea of how vaccines will work against the variant. But more definitive data will require data on human populations.

How long will the lab experiments take, when will we know more?

“Many labs are starting to work on this and hopefully, the data that will come out will be very consistent and tell us exactly what’s going on,” said Corey. “In my opinion, it’s going to take ten days to two weeks to get anything that really is an accurate read.”

What types of data will be collected in human populations in South Africa?

“Working with the South Africans, who are measuring the outbreak of the disease there, is important,” said Corey. The country is about 30% vaccinated, mainly with Pfizer/BioNTech and Johnson & Johnson shots, enabling comparisons between vaccinated and unvaccinated populations. Researchers can collect data such as hospitalization rates and disease severity in vaccinated and unvaccinated individuals, said Corey. “All this kind of information is needed on the ground for us to understand just what the extent of this outbreak will be.”

Omicron (in red) has a high number of mutations in a region of the ‘spike’ protein (S1) compared to other variants. (Nextstrain Plot)

Will Omicron make it to Washington state?

Roychoudhury says there is a good chance there are already cases in the state. “And if that is the case, we will eventually catch it [with our testing],” said Roychoudhury. “It’s already reached a number of European countries and so we think that it’s just a matter of time, based on what we’ve seen of the other variants and how long it took for us to detect them here. There’s been a lot of travel over the last several months.” It is unclear, however, if the variant has the capacity to outcompete Delta, the current dominant strain in the U.S. and much of the world.

How are UW researchers looking for the variant in Washington?

The UW lab performs a large proportion of the state’s COVID-19 testing, lately averaging about 10,000 PCR tests per day (PCR tests are the more accurate molecular tests that generally take overnight for a result). The lab also samples positive samples randomly for the variant type using whole-genome sequencing. Washington state has one of the highest rates of variant testing of any state, testing about 11% of COVID-19 positive samples since the start of this year, said Roychoudhury.

How could UW testing data help answer questions about Omicron?

Broad testing for variants can help researchers understand key questions, for instance how fast a variant is spreading and the links between infection and hospitalization and vaccination, said Roychoudhury. “Is it more transmissible? Is it causing more severe disease?” she said. “And is it evading current vaccines and making vaccinated people sick? And then is it taking vaccinated people into the hospital?”

“They are heroes, for being so open and helping us.”

How did Omicron emerge?

Nobody knows for sure how Omicron arose. But Corey has a hypothesis.

One way new viral strains can arise is by incubating within an immunosuppressed individual long term. That gives the virus time to evolve, adapting to infect cells more efficiently or to better evade the immune response.

Corey wrote about evidence for this route of COVID-19 virus evolution in a recent publication with Fred Hutch researcher Trevor Bedford and other colleagues. “Unfortunately, that’s likely what happened here,” said Corey.

“It probably came from an immunosuppressed person with longstanding COVID that developed this, and was then transmitted within families, then within communities,” he said. “And then we had maybe a couple other transmissions as it adapted a little bit. That’s how these strains arrive.” 

Corey added that the rise of the new variant “illustrates the importance of global vaccination policy.” Not only is vaccine supply limited in some countries, vaccine hesitancy in South Africa and other areas also impedes vaccine uptake, said Corey.

How do the HIV epidemic and COVID-19 pandemic intersect?

Corey notes that untreated HIV-positive individuals may have potential to incubate COVID-19 virus long term. “The most common immunosuppressed person in in sub-Saharan Africa is the untreated person with HIV infection. So, you have two intersecting epidemics,” said Corey. “Sub-Saharan Africa has the highest rate of HIV untreated people in the world. So, we need to improve how we handle HIV, especially treatment, as well as involving COVID vaccination strategy with HIV identification and treatment strategy.”

What are your colleagues in South Africa saying about the world’s response to Omicron? Some countries have implemented travel bans.

“They want to make sure that flights into the country are not stopped because they need the scientific equipment and the supplies to do the research work,” Corey said. “And so we have to not treat them as pariahs either.” Though buying time before variants spread can help countries prepare, Corey favors increased testing at airports and other measures to detect and contain COVID-19 positive travelers over blanket travel bans.

Added Corey: “They are heroes, for being so open and helping us.” 

Is it possible vaccine companies may need to reformulate their shots?

Corey oversaw the record-time launch and completion of clinical trials for Moderna, Johnson & Johnson, and other shots, so he knows how to move rapidly. If vaccines need to be reformulated to combat Omicron or another new variant in the future, how long would that take? “We will do it as quickly as humanly possible,” he said.  

But until more experiments are completed and more data collected, scientists will not know how well current vaccines will protect against Omicron, how widely the variant will spread, how infectious it will be, and other key questions.

Meanwhile, the U.S. Centers for Disease Control on Monday urged unvaccinated people to get their shot and strengthened its recommendations for COVID-19 shots, saying that everyone 18 and older “should” get a booster. Previously the CDC had said some adults under 50 “may” get a booster.

Added Corey: “I can honestly say boosting is a very good strategy. You want all the antibody you can have.”

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