COVID-19 in Oregon

When the variant now known as omicron first appeared on a global database of coronavirus genomic sequences, scientists were stunned. This was the weirdest creature they'd seen to date. It had an unruly swarm of mutations. Many were known to be problematic, impeding the ability of antibodies to neutralize the virus. But there had never been a variant with so many of these mutations gathered in a package.

Even though scientists recognized some of these mutations, many others were new and utterly enigmatic.

"We have seen these mutations in other strains, in twos and threes, and each time they were a little harder to neutralize, but didn't spread particularly well. Now, all together? It's a complete black box," Benjamin Neuman, a virologist at Texas A&M University, said in an email.

Of the many questions about omicron, the overriding one is whether it's as bad as it looks at first glance.

President Joe Biden on Monday expressed confidence that the United States can handle the new variant.

"This variant is a cause for concern, not a cause for panic," Biden said. "We'll fight this variant with scientific and knowledgeable actions, and speed, not chaos and confusion."

In a preliminary technical brief, the World Health Organization said the "overall global risk" from omicron is "very high," and recommended that governments worldwide enhance their ability to sequence coronavirus variants, report local cases of omicron to the global health body and accelerate their vaccination drives.

In remarks prepared in advance of congressional testimony Tuesday, Federal Reserve Chair Jerome Powell warned that the recent rise in coronavirus cases in the United States and the emergence of omicron "pose downside risks to employment and economic activity and increased uncertainty for inflation."

The significance of omicron pivots on several unknowns. Is it more transmissible than the delta variant? Can it cause more severe illness? And can it erode or even completely evade immunity, whether induced by vaccines or previous infections?

Earlier variants, including alpha and delta, had mutated in ways that enhanced their transmissibility. But scientists have long feared the possibility that the coronavirus, SARS-CoV-2, would evolve to become a more slippery, elusive pathogen - evading, even if only partially, the early lines of defense from the immune system, including neutralizing antibodies.

There are other elements of the immune system, such as "killer" T cells, that provide backup protection, and they are likely to provide protection from severe illness even for new variants such as omicron, infectious-disease experts think.

Omicron has about 30 mutations scattered on three major prongs of the spike protein that is essential to the virus's ability to infect cells. Disease-fighting antibodies that can potentially neutralize the invading virus target those spike proteins. The mutations change one amino acid to another in a way that can alter the structure or chemistry of the protein and prevent antibodies from binding as they normally would.

Unfortunately, mutations don't come with handy explanatory labels when they appear in a genomic sequence. And no one can tell how multiple mutations would work as a team - whether they would turn the virus into something even more dangerous than the delta variant or somehow sap omicron's powers.

"Omicron is like the song 'One Piece at a Time' by Johnny Cash, where he puts together a car from stolen bits of lots of different cars. It is made of mutations that were somewhat successful separately in other variants, but together it is hard to say more than it looks weird," Neuman said.

Scientists don't want to get ahead of the facts: No one knows yet how this variant behaves in real-world situations. But if it has a high degree of immune evasiveness, vaccine makers will have to revise their formulas, something already in the works at a preliminary stage. This would be a major setback in the world's efforts to emerge from a pandemic soon to enter its third full year.

The other possibility: Omicron could go the way of alpha, beta, lambda, gamma, mu and other variants that had worrisome mutations and a period of notoriety but were driven virtually to extinction by the more transmissible delta variant.

"We're in a delta pandemic now. Does this outcompete delta? To be determined," said Robert Garry, a virologist at Tulane University who has scrutinized the mutations in omicron. "Delta's a pretty good virus, right? It's good in terms of being transmissible. This one would have to show some extraordinary characteristics to outcompete it."

Kristian Andersen, an immunologist at the Scripps Research Institute, said in an email, "The only thing I have somewhat moderate confidence in is that I think this'll be the most immune evasive variant we have seen to date. Other than that, it's simply too early to tell - on a scale of 1-10 of how bad this is, it's either a 3, a 10, or anywhere in-between."

Laboratory experiments can help characterize whether mutations are consequential or just a random change of no great significance. But omicron is so new that it has not yet been sent through a gantlet of laboratory tests.

"It looks grim, but it needs to be tested and we don't know how these mutations will act together," said Bette Korber, a theoretical biologist at Los Alamos National Laboratory.

Omicron may not have been fully tested in direct competition with delta. The delta variant, first identified in India early this year, is at least twice as transmissible as the first version of the coronavirus identified in Wuhan, China, nearly two years ago. By summer, delta had routed virtually every other variant on the planet.

South Africa, now late in its springtime, was experiencing a low level of viral transmission before omicron appeared and started a cluster of infections. That cluster could have represented a random superspreader event rather than a clear signal of greater transmissibility of omicron.

Experience offers some hope that omicron could fade as a threat. Other variants - for example, mu - have appeared with mutations that are known to lower the potency of antibodies. But that immune-escape advantage was not enough to overcome a relative weakness in other mechanisms that enable infection. So when the mu variant appeared in Southern California, it generated headlines for a week or two before being crushed by delta.

The origin of omicron is unclear. It came out of a remote part of the virus's family tree. It is not a descendant of delta, although it shares some of delta's mutations. With testing and genomic surveillance spotty in some regions, scientists aren't sure how long this variant has been in circulation. It is possible that omicron has gradually evolved in the human population and simply remained below the radar of the scientific and medical establishments.

Another possibility, still speculative but discussed by many scientists in recent days, is that omicron evolved over many months within an immunocompromised patient with a protracted infection. In a patient treated with therapeutics such as monoclonal antibodies or convalescent sera, a viral strain that can survive the assault can potentially amass a host of mutations. Such cases have been documented, but they are not known to have led to outbreaks in the general population.

Andersen favors another conjecture: That the virus possibly came from an animal. He bases that on the array of mutations not previously seen in humans. The coronavirus is a generalist pathogen that can pass from humans into animal populations - and potentially back again.

The coronavirus has mutated steadily, at a fairly leisurely pace. Some of the mutations that stick around, becoming embedded in the genetic code of the virus going forward, have offered an advantage to the "fitness" of the virus, for example by firming up the spike protein on the surface of the virus and improving its ability to bind to receptor cells.

It is possible that omicron is not as transmissible as the small data set from South Africa has suggested. The discovery of a cluster of omicron infections in a university may have led officials to oversample that population in further testing.

Likewise, the lack of data to date has prevented scientists from reaching conclusions about whether omicron is more capable of causing severe disease. South African officials have said they have not seen evidence of a surge in severe illness. Angelique Coetzee, the South African doctor who treated the first omicron patients there, said her patients so far have tended to have mild or asymptomatic cases. Most of the early South African cases have been among younger people, who are less likely to have severe infections from the virus generally.

Public health officials continue to push vaccination, including booster shots, as the best way to prepare for a new coronavirus variant.

"You have to get your vaccine. You have to get the shot. You have to get the booster," Biden said.