Shared from the 12/5/2021 San Francisco Chronicle eEdition

Local omicron case will aid scientists

Sample gives Bay Area researchers head start in race to study variant

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Jessica Christian / The Chronicle

Dr. Charles Chiu, the UCSF scientist who led the team that identified the omicron coronavirus variant in San Francisco, has fielded multiple requests from scientists for study samples.

Finding the omicron coronavirus variant in San Francisco on Wednesday may have caused concern among the general public, but to the Bay Area scientists eager to study the highly mutated virus and understand the threat it may pose, having a sample in their backyard was a stroke of luck.

In the mad global dash to study omicron, getting copies of the variant to analyze in U.S. labs has been a challenge. Some Bay Area scientists said they’ve been on waiting lists for at least a week — since Thanksgiving, when the variant was first reported out of South Africa.

With more cases identified every day in the United States and hundreds now around the world, soon there will be plenty of viral material to go around. But the San Francisco sample could give local scientists a head start on studies that will help them determine how infectious omicron is and how well the current vaccines perform against it.

Already, labs around the region have started, or will within a few days, surveys that test omicron against test antibodies drawn from people who are fully vaccinated or were previously infected with earlier variants. Key local studies will seek to define how well specific vaccines work against omicron and how much extra protection is offered by boosters.

Local scientists also will study how the variant binds with human cells and whether its mutations make it easier to infiltrate and tougher to fend off.

The most important studies, which will tell scientists and public health officials how omicron performs in the real world, will take months to complete. But early lab research should give critical clues as to what omicron may be capable of, scientists said.

“The data coming out of South Africa in the last two days is a little concerning in omicron’s ability to replace delta,” said Dr. Catherine Blish, a Stanford infectious disease expert who is eager to start studies into how the body’s early immune response fares against omicron. “But we’ll see how the lab experiments compare.”

So far there are troubling signs that omicron is more infectious than delta, which is already more than twice as infectious as the original strain of virus that kicked off the pandemic nearly two years ago.

Omicron is supplanting delta as the dominant variant in South Africa, and early reports suggest it may be spreading twice as fast. Cases have been popping up around the globe even as many countries established new restrictions on travel to try to contain it.

Delta remains dominant in most of the world, including the United States, where it makes up 99% of cases. And delta, not omicron, is causing spikes in some parts of the country that could lead to a new winter surge. Vaccines are proving effective at preventing severe illness and hospitalizations, and public health officials don’t expect a disastrous surge in well-vaccinated places such as the Bay Area, even if cases climb.

It’s too soon to say if omicron would change that forecast, scientists say. Even if it turns out to be much more infectious than delta, that may not matter if it only causes mild disease and if the vaccines continue to provide strong protection.

And if the vaccines don’t hold up quite as well against omicron as they have against delta, that could translate into more breakthrough cases but not necessarily more hospitalizations.

Almost everything scientists suspect about omicron so far is speculation. What the world needs is “hard-core laboratory data,” said Joe DeRisi, co-president of the Chan Zuckerberg Biohub in San Francisco.

His Biohub colleagues requested samples of the variant from South Africa the same day it was reported, but they weren’t expecting anything to arrive until Monday. So they jumped on the chance to get a sample from Dr. Charles Chiu, the UCSF scientist who led the team that identified omicron in San Francisco.

Their first studies are looking at how well the vaccines work against the variant, DeRisi said.

“Other people want to grow the virus and do animal models. Other groups might want to measure how fast it replicates in culture,” he said. “There’s a whole arsenal of different assays that laboratories will do with this variant, as soon as there’s sufficient material to pass around.”

Hours after finding the variant, Chiu said he’d had requests from about a dozen U.S. scientists who wanted access to the sample. Like the Biohub team, Chiu also planned to study how well the variant evades antibodies elicited by vaccination or previous coronavirus infection.

To understand antibody effectiveness, scientists perform what are called neutralization assays. They collect blood serum from people who have been infected with any strain of the virus previously, and others who have been vaccinated; ideally they have serum that represents all three of the vaccines in use in the U.S., and from people who have had boosters as well as those who have not.

They soak the variant in samples from the different serums, then mix the antibody-drenched virus with human cells in petri dishes to test how well it is able to infect them. Simply, scientists will count how many cells end up infected. That kind of study allows for a head-to-head comparison of variants, as well as different types of antibodies.

Results of antibody neutralization studies could be available in two to three weeks. Most of that time is spent simply growing the virus — getting enough of it to conduct the studies. The actual neutralization assay only takes a few hours.

There are still real-life variables that may make antibodies more or less effective against a variant than what scientists can learn from the lab. For example, a lab study can’t tell doctors how well two shots of Pfizer and a booster will do at keeping an 80-year-old patient out of intensive care.

But lab research could give scientists an early warning if there’s a notable drop in antibody effectiveness against omicron. Or, more optimistically, the studies could offer comfort that the antibodies remain strong protectors.

“The key experiments are neutralization assays with the existing serum. I’m sure this is being done already in Africa, but it will be very important to do them in multiple places, because we have different vaccines and people have different boosters,” said Dr. Melanie Ott, director of the Gladstone Institute of Virology.

Studying how infectious a variant is in a lab is somewhat more complicated than studying antibody effectiveness. What makes a variant more infectious can depend on a variety of factors, such as how well the variant latches onto cells or how quickly it replicates. Delta is thought to be so highly infectious in part because it reproduces much faster than earlier variants.

Neutralization studies can be done using what’s known as pseudovirus — a synthesized version that includes what are likely the most important mutations located on the spike protein, the part of the virus used to infiltrate a cell. But pseudovirus isn’t able to replicate, so it can’t tell scientists all they need to know about how infectious a variant is. That requires live virus.

Scientists will use the live virus to study how omicron behaves in human cells and in animals. As with neutralization studies, real-world evidence will be most important for figuring out how infectious the new variant is — but that will require thousands of cases to study, which thankfully isn’t yet possible in the U.S.

Determining whether a variant causes more or less serious illness is even more complex, and essentially impossible to do in a lab. It’s even tough to do those studies in the real world, where social factors — such as the age of the population, access to health care and how widespread the disease is — can all influence outcomes.

“The laboratory is not where the story ends,” DeRisi said. “These studies are a proxy for what happens in the real world, but they’re not reality. The true data will come from household and population epidemiological studies.”

The world should know much more about omicron — and how it may shape the tail end of the pandemic — in another two to three weeks.

Many scientists said, though, that they are cautiously optimistic that in well-vaccinated places like the Bay Area it won’t change the path toward the finish too dramatically.

“If we are smart, we can weather this,” Ott said. “We don’t have to do a lockdown, we don’t have to not interact with anybody. If I have to keep wearing a mask in the supermarket a little longer, I’m not going to lose sleep over it. I have faith in the people here in the Bay Area, they will understand what to do.”

Erin Allday is a San Francisco Chronicle staff writer. Email: eallday@sfchronicle.com Twitter: @erinallday

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