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Omicron: what we know, what we need to find out, and… what now?

It’s been a long year of worrisome news reports about COVID-19 variantsAlpha, Beta, Gamma, Delta, Lambda, Mu. And now Omicron.

The latest coronavirus variant, initially known as B.1.1.529, was discovered on November 11 in Botswana. South Africa reported the variant to the World Health Organization (WHO) on November 24 after it was found to account for a majority of new cases in the province of Gauteng, which includes the densely populated cities of Johannesburg and Pretoria. Within two days, the WHO had renamed the variant with the Greek letter Omicron and declared it a variant of concern (VOC), citing its large number of mutations — 32 on the spike protein alone. The pronouncement led to plunging stock markets, travel bans, and endless speculation about Omicron’s potential to spread more easily, cause more severe disease, and evade vaccine-induced immunity.

Variant family tree illustration

“But if there’s one thing we should have learned by now,” says Medical Director Cecilia Stuopis, “it’s to wait for the data.” In the case of Omicron, she explains, that wait is likely to be a matter of several weeks. “Previous variants were known and circulating for months before the WHO designated them as variants of concern,” she notes. “That gave scientists time to study them and answer questions about how transmissible or lethal they might be.”

When it comes to Omicron, two big questions remain:

Is Omicron more contagious than previous variants?

We still don’t know. Some observers point to the surge of Omicron cases in South Africa’s Gauteng province as evidence of the new variant’s ability to “outcompete Delta.” Others note that, until very recently, this region of the country had very few cases, its lowest number since the start of the pandemic, meaning Omicron might not have had much competition. This void in which a new variant could spread more readily — combined with a vaccination rate of less than 25 percent — would have been ideal conditions for a “founder effect,” a situation in which a single case in an area of low prevalence, combined with a superspreading event or two, results in a rapid spread of disease. In places like the US, where Delta is dominating and a higher proportion of the population is vaccinated, Omicron faces a greater challenge.

But what about all those mutations on the spike protein? “It will take some time to know how those mutations affect viral fitness,” Stuopis explains. “Some could make it easier for the virus to spread. Others could have the opposite effect. But more mutations don’t necessarily make a more dangerous variant.”

And it’s not just about the spike protein. Trevor Bedford, a genome scientist and epidemiologist at the University of Washington and Fred Hutchinson Cancer Center in Seattle, points out that Omicron lacks many of the non-spike mutations that appeared to make the Delta variant more transmissible. Referencing a recent Broad Institute study of those mutations, he says, “I wouldn't be surprised if [Omicron’s] intrinsic transmissibility is similar to Gamma,” a variant that proved unable to outcompete Delta.

Still, while we are waiting for more data, it’s safest to assume that Omicron is highly transmissible and act accordingly, Stuopis says. “New cases attributable to Omicron have been identified in many additional countries in the last few days,” she observes. “Continuing close surveillance will provide crucial information that we don’t have now. Omicron will have more competition outside of South Africa, and the next few weeks will tell us a lot about how its actual transmissibility compares to Delta and prior variants.”

Can Omicron evade immunity provided by vaccines?

This is another question we can’t answer yet. “However,” Stuopis emphasizes, “the answer will not be a simple ‘yes’ or ‘no.’ Immune escape will be a matter of degree.”

The degree to which this new variant can evade the immunity induced by vaccination or natural infection is something else we’ll learn more about in coming weeks. It’s information that will come from both laboratory studies and real-world data. “Vaccines may well be less effective against this variant,” Stuopis acknowledges. “That’s probable, in fact. But it’s very likely that vaccination will continue to be protective against severe disease.”

That’s because both vaccines and natural infection lead to the creation of “polyclonal antibodies” — antibodies that come in many different shapes to be able to bind to many different target sites on the surface of the virus. Mutations that affect those target sites, such as those seen with Omicron, might mean that some of our antibodies will not be able to bind to the new variant, or might not bind as completely. But even if a new variant manages to dodge some of our antibodies, it’s probably not going to dodge them all. In fact, a recent study of naturally occurring and laboratory-created mutations found that any SARS-CoV-2 variant would need to contain approximately 20 of exactly the right kind of mutations to be fully resistant to the antibodies produced by the typical, fully vaccinated individual.

But while there are early indications that vaccines will be at least somewhat protective against serious illness caused by the Omicron variant, concerns about possible immune escape likely fueled the CDC’s new recommendation earlier this week, that all eligible adults get booster shots as soon as possible. It’s a recommendation Stuopis supports. “Boosters remind the immune system that this coronavirus is a continuing threat,” she explains. “A booster increases the number of circulating antibodies, and even if a variant can evade some of those antibodies, sheer numbers give you an immediate advantage if you are exposed.” A recent preprint study also showed that boosters generated an even wider range of antibodies that could target more parts of the virus.

What do we do now?

While Stuopis acknowledges the frustration of having more questions than answers, she assures us that we’ll be getting those answers soon. In the meantime, she advises aiming for that sweet spot between panic and complacence and trying to block out the constant drumbeat of speculation. “We need to take the threat of new variants seriously,” she emphasizes, “but Omicron is not a new virus. We know how to protect ourselves and our community by doing what has worked so far — wear a mask indoors; get tested even if you have mild symptoms, and self-isolate until you get the results; isolate if you test positive; get vaccinated; and get boosted.”

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