What Hutch coronavirus experts are saying about omicron

Some answers, but many questions, about highly mutated new variant of COVID-19 virus
Image of a colorized transmission electron micrograph of a SARS-CoV-2 virion isolated from a patient
A colorized transmission electron micrograph of a SARS-CoV-2 virion isolated from a patient. Photo by the National Institute of Allergy and Infectious Diseases

Editor's note: This story was first published on Nov. 29 and regularly updated through Feb. 11. We do not plan further updates. 

Since its sudden appearance in late November, the omicron variant has upended expectations about the course of the COVID-19 pandemic, and Fred Hutchinson Cancer Research Center scientists remain in the forefront of efforts to make sense of it.

In this story, we provide the latest on what Hutch researchers are saying and tweeting about the new variant.

In a Feb. 10 story in The New Yorker, Fred Hutch computational biologist Dr. Trevor Bedford discussed new evidence suggesting that the multiple mutations that distinguish the omicron variant may have first occurred in mice who had picked up COVID-19 from humans. Bedford called the hypothesis, as laid out by Beijing researcher Dr. Wenfeng Qian in the Journal of Genetics and Genomics, "the most compelling case for rodent origin I've seen."

He still favors the current, widely held view that omicron likely evolved while "replicating for months" in a patient who was immune-compromised, perhaps by an active HIV infection, but concedes that he is "definitely not certain."   

In another recent development, Fred Hutch infectious disease specialist Dr. Catherine Liu said on Feb. 1 that a subvariant of omicron, known to scientists as BA.2, may be spreading faster than the original variant, called BA.1, that emerged suddenly in southern Africa late last November.

Link to Science Says interview of Dr. Catherine Liu by Dr. Tom Lynch
Fred Hutch President and Director Dr. Tom Lynch (upper left) interviews infectious disease specialist Dr. Catherine Liu (bottom) during an online Science Says session on Feb. 1, 2022. Click to view on YouTube

In the online Science Says interview with Dr. Thomas J. Lynch, president and director of Fred Hutch, Liu said BA.2 may be outcompeting the original omicron variant in Denmark, India and parts of Asia, but it does not appear to have altered the declining trajectory of COVID-19 in the U.S.

She told Lynch, who holds the Raisbeck Endowed Chair, that both locally and in other parts of the nation, “the case counts have started to decline, which is positive news for everybody.”

“The good news is that the data seem to suggest there does not appear to be increased severity of illness associated with BA.2, and preliminary data from the U.K. suggest that the booster doses offer similar levels of protection against BA.1 and BA.2,” Liu said.

Antivirals, antibody drugs and omicron

Physician-scientist Dr. Elizabeth Duke, who has been overseeing trials of the antiviral drug molnupiravir at the Hutch's COVID-19 Clinical Research Center, discussed the impact of omicron on authorized antiviral drugs in a Jan. 28 article in Popular Science.

While omicron and its BA.2 "sister" subvariant are more likely to cause breakthrough infections among those vaccinated, antiviral pills or the intravenous drug remdesivir still seem to retain their effectiveness in preventing hospitalizations.

Extensive mutations on the spike proteins that dot the surface of the coronavirus are responsible for diminished effectiveness of vaccines that target the spike. They also have rendered some of the spike-targeting monoclonal antibody drugs ineffective. But the antiviral drugs molnupiravir, remdesivir and Paxlovid target processes at work within the virus, rather than the spikes. 

“Based on the mechanism of the antivirals I would expect it to work against omicron and also future variants," Duke said. “It’s really nice to have the antivirals as a complementary part of our treatment approach, and this is something that is coming out at just the right time."

Omicron adds uncertainty to forecasts

NBC News noted on Jan. 28 that the sudden emergence of omicron is making it more difficult to forecast the direction the COVID-19 pandemic will take.

“I have just been so humbled and surprised by these variants of concern and the number of unanswered questions we have about them, where they came from, why they arise,” said Fred Hutch virologist and disease modeler Dr. Joshua Schiffer told NBC news reporter Evan Bush. "It’s difficult to project whether one of the viruses will permanently displace another or whether they’ll coexist in the population or whether a new variant will displace both of them.”

Also on Jan. 28, Bedford delivered in a Twitter thread a tutorial on the BA.2 subvariant. His view is that, while this new version will likely lengthen the time it takes for the current omicron wave to fade, "it won't drive the scale of epidemics we've expericenced with omicron in January."

In his new thread, Bedford charts of the family tree of COVID-19 variants. The original BA.1 omicron variant is labeled in his Nextstrain system as 21K, and its newer cousin BA.2 is called 21L.

Tweet from Trevor Bedford (@trvrb) that reads: For comparison Alpha, Beta and Gamma are each about as divergent from each other in terms of amino acid changes across the genome as Omicron 21K and 21L are from each other. Figure from  @nextstrain  (https://nextstrain.org/ncov/gisaid/global?l=unrooted&m=div). 3/15
Click to view complete thread on Twitter

Earlier, Fred Hutch virologist Dr. Larry Corey appeared on Seattle's KING 5 News on Jan. 26 to discuss the BA.2 subvariant of omicron. He said that the subvariant behaves the same as the original omicron, so it is not uniquely concerning.

"There's much ado about nothing," Corey said.

Fred Hutch virologist Dr. Larry Corey and other infectious disease experts explain on KING 5 News what the BA.2 subvariant of omicron means for the Seattle area.


Tracking the omicron wave

Bedford and other experts also  spoke to Science for a Jan. 25 story looking ahead to the pandemic's trajectory as the omicron wave wanes in many countries. Many of these experts anticipate a period of quiet and have a sense of optimism that, in many places, the worst may be over. The U.S., however, with its relatively low vaccination rate, still had more than 2,000 deaths per day by late January. And Bedford cautioned that it is possible that the delta variant, which was predominant in the U.S. until the arrival of omicron, could make a comeback.

“If there is still some delta circulating in September, then I think you can have coexistence,” Bedford said. “And that would add to your burden of disease and add to complications in vaccination.”

On Jan. 19, Bedford wrote a series of nine Tweets explaining the current state of omicron infection in the U.S. While COVID-19 case counts in the U.S. overall had already peaked by that date, they had yet to peak in many individual states. The data suggested that around one in five Americans were infected by omicron by mid-January, he explained, a proportion likely to double by mid-February — a "remarkable" rate for which he could find no obvious precedent in modern history:

Tweet from Trevor Bedford (@trvrb) from 6:55 p.m. on Jan. 19, 2022. A graph of US daily cases shows a dramatic peak around the beginning of January to roughly 800,000. Text reads: Case counts for the US appear to have peaked at a 7-day average of 806k on Jan 14. Omicron grew from approximately 35k daily cases on Dec 14 to ~800k daily cases in ~4 weeks. 1/9
Click to view on Twitter

It's still unclear, he wrote in that Jan. 19 thread, how frequently variants like omicron will emerge.

On Jan. 10, Bedford explained in a thread of 15 tweets his startling conclusion that up to 1% of the U.S. population at that time was being infected daily by SARS-CoV-2.

He based his reasoning on an assumption that infection rates in the U.S. were considerably higher than infections reported through testing, and by comparing data from the U.S. to that from the U.K., which has a more robust system of COVID-19 surveillance:

Screenshot of Tweet 15/15from Bedford lab on Jan. 10 that states: Given ~680k cases per day, this would in turn suggest 0.8% or 1% of the US being infected with SARS-CoV-2 every day. This would translate to perhaps 5% or 10% of individuals currently infected with SARS-CoV-2 in the US.
A thread from Dr. Trevor Bedford on Jan. 10 explaining his estimate that up to 1% of Americans are being infected with SARS-CoV-2 daily. Click to view on Twitter

Far more heavily mutated than its predecessors, omicron was detected in late November thanks to scientists in southern Africa who have set up a robust system for sequencing coronavirus samples. The data reached the global scientific community right away courtesy of the open science infrastructure, including use of non-peer reviewed preprints and Twitter posts, which have helped speed the world’s response.

Bedford addressed another open question as to why omicron's wave of infection in Gauteng, South Africa, crested quickly. In a New York Magazine interview, published on Dec. 18, he discussed five possible reasons, including limited testing capacity, underreporting of infections due to a drop in severity, a change in the virus's generation interval, limited population susceptibility and the possible impact of a network effect, referring to the fact that all humans aren't socially connected to other humans equally.

‘A huge jump’ in SARS-CoV-2 evolution

Meanwhile, Hutch evolutionary biologist Dr. Jesse Bloom has been exploring the possible impact of individual mutations in the SARS-CoV-2 genome. He told The Atlantic for a Dec. 8 story that "omicron was a huge jump in evolution," and explained that in apparently just a few months the virus changed as much as he and many researchers expected it to change “over the span of four or five years.”

The majority of mutations in omicron’s genome are in the code for the virus’s spike protein. The spike is the key that allows the virus to gain entry to human cells and is the target that our current vaccines train our immune systems to recognize.

In recent weeks, Bloom and his lab colleagues have been evaluating how multiple mutations might interact — a phenomenon called “epistasis” — and affect transmissibility of the virus. He discussed the concept in a New York Times article published on Nov. 29 by journalist Apoorva Mandavilli, who wrote, “mutations sometimes work together to make a virus more fearsome, but they may also cancel one another out.”

In a Dec. 31 Twitter thread, the Bloom Lab expanded on omicron epistasis with new data. It explains that most individual mutations near the tip of the omicron’s spike actually decrease binding to the ACE2 receptor, the critical point SARS-CoV-2 uses as a gateway into human cells. But viral evolution nevertheless “selects for combinations of mutations that work well together,” leading to better binding.

Bloom’s 10-tweet thread, citing the work of numerous researchers around the globe, pinpoints two mutations that, together, cause the spike to bind to the ACE2 receptor better than the original coronavirus that emerged in Wuhan, China:

Screenshot of Tweet from Bloom Lab (@jbloom_lab) on Dec. 31, 2021 that reads: I want to follow up on below discussion from last month to highlight some new datat on role of epistasis (interactions among mutations in #Omicron #SARSCoV2 variant, and place this example in the context of protein evolution more broadly. (1/n)
A thread from Dr. Jesse Bloom's lab introducing a 10-tweet thread discussion on the role of interactions among SARS-CoV-2 variant mutations. Click to view on Twitter

Modeling omicron’s spread

Fred Hutch infectious disease modeler Dr. Joshua Schiffer and colleagues are modeling how omicron will likely spread within one community — the Seattle area where the Hutch is located. In a Dec. 31 story, Schiffer told NPR that omicron has been spreading as fast as the original strain of the coronavirus at the beginning of the pandemic, despite the immunity we now have.

"The playing field for the virus right now is quite different than it was in the early days," Schiffer said. "The majority of variants we've seen to date couldn't survive in this immune environment."

Even delta was essentially at a "tie," he told NPR, where it was persisting, but "not growing very rapidly or decreasing very rapidly."

High rates of asymptomatic omicron infection

Fred Hutch virologist Corey is the senior author of a paper posted on the preprint server medRxiv on Dec. 27 detailing a South African study showing that omicron appears to have a much higher rate of “asymptomatic carriage” — nasal swabs testing positive for SARS-CoV-2 in people who have no obvious symptoms of the disease.

The preliminary findings, part of a study that provided extensive testing of people living with HIV who received COVID-19 vaccines, found positive results in 32% of samples, about seven to 12 times more than found in prior studies before the emergence of the omicron variant.

“As we witness the quick, global spread of omicron, it is clear that we urgently need a better understanding of the transmission dynamics of this variant,” Corey said in a press release. “Since so many people may be asymptomatic, we can’t always know who is carrying the virus, but we do know what we can do to protect ourselves and to help prevent further spread: Wear a mask; wash your hands; avoid large, indoor gatherings; and get fully vaccinated as soon as possible.”

Evidence that boosters protect against severe illness

By the end of December, experts said that the evidence from several countries indicates that healthy people who have been vaccinated, especially if they’ve received a booster, were unlikely to require hospitalization if they became infected with omicron. But since the variant spreads easily and is infecting many people, including many who are vulnerable, this still means that a lot of people need to be cared for in already short-staffed hospitals.

“We need to be respectful of the fact that our hospital system has been under this kind of duress for such a long time,” Corey told the Washington Post on Dec. 28. “We need to do everything we can to not allow the situation, where there’s such crowding and such intensity that we can’t optimally take care of the people who get severe disease.”

On Jan. 6, Corey told KXLY TV in Spokane, Washington, that scientists should know soon whether a reformulated booster, specifically tailored to block omicron, will be needed.

“We’re looking at omicron vaccines and what we’ll call the ancestral strain vaccines. I think for us we want to see if the immune responses to the omicron variant is better than ancestral strain and when we know that, probably by the end of February, we’ll pull the trigger on what’s the next best approach for another boost,” he said.

Left to right: Drs. Joshua Schiffer, Larry Corey and Elizabeth Halloran
Left: Dr. Joshua Schiffer. Top: Dr. Larry Corey. Bottom: Dr. Elizabeth Halloran

Photos by Robert Hood / Fred Hutch News Service

Endemicity in our future?

It now seems clear that SARS-CoV-2 will not be eradicated. It will become endemic, meaning always circulating within populations of people. So, what does a future of endemicity look like?

Dr. Elizabeth Halloran, an expert in infectious disease modeling and the design and analysis of vaccine trials, noted in a USA Today story on Jan. 9 that “endemic” is not a synonym for “no big deal.”

“We could have an endemic state where disease burden is still unacceptable, if it stays very severe,” she said. While many viruses evolve to be less dangerous over time, and omicron looks to cause relatively mild infections in healthy people who are up to date on their coronavirus shots, we don’t yet know if this will be the trajectory for SARS-CoV-2, she said.

"It could evolve to be less severe. That's what my expectation is. But it's surprised us a couple of times already,” she said, adding that the development of variant-specific boosters may be wise. 

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