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Why firm answers about Omicron's impact could take weeks - STAT

The emergence of the Omicron variant of the coronavirus, with a suite of mutations that suggests it might be extra transmissible and be able to evade at least some immune protection, has the world eager for answers about what it means for the Covid-19 pandemic. But so much remains unknown largely because the variant appears to have been detected and publicized so quickly.

With other variants, a matter of months passed between the time they were first documented until they were designated “variants of concern” — in some cases giving scientists more opportunity to understand them before they attracted widespread attention. With Omicron, initially identified as B.1.1.529, it all happened within about two weeks.

As they race to launch more rigorous studies, scientists for now are trying to glean insights from limited epidemiological evidence in South Africa and from the list of mutations the variant has acquired, some of which are associated with an increased ability to spread or to get around immune protection. The variant is also notable for its sheer number of mutations:  32 alone in its spike protein, which is what the vaccines teach our immune systems to target. Other variants just had a handful of mutations in spike.

“Right now there are many studies that are underway,” Maria Van Kerkhove, the World Health Organization’s technical lead on Covid-19, said Friday. “There is a lot of work that is ongoing in South Africa and in other countries to better characterize the variant itself, in terms of transmissibility, in terms of severity, and any impact on our countermeasures, like the use of diagnostics, therapeutics, or vaccines. So far, there is little information, but those studies are underway, so we need researchers to have the time to carry them out.”

She added: “It will take days to weeks for some of these studies to be undertaken.”

The scientists who have conducted the early research on Omicron stress they don’t know if the variant will have a major impact globally. But they have reasons for concern, which is why they’re urging nations to prepare and act early.

For now, perhaps the most pressing questions about Omicron are: Is it more transmissible than even the Delta variant, and if so, how much? And to what extent can it evade immune protection generated by earlier infections or vaccines?

On the transmissibility question, experts will watch closely to see how Omicron continues to play out in South Africa and elsewhere.

Early epidemiological data suggested that Omicron was racing ahead of Delta in South Africa, and even replacing it faster than Delta did other variants. (A potential spreading advantage could mean the variant is inherently more transmissible, able to cause infections in people who are protected at higher rates than other versions of the virus, or some combination of the two.)

Levels of Covid-19 in South Africa were subdued when the variant was first detected; since that time numbers have jumped. It’s possible that means Omicron has a growth advantage over Delta, but it’s also possible that it’s riding the new surge of cases, not driving it. Some scientists hypothesized that the rise in cases has been propelled by some superspreading events, explaining why a surge was first detected primarily in Gauteng province. Now, however, cases from the variant are increasing around the country, the WHO said, but some of the increase could be tied to which infections are being sequenced.

If Omicron establishes toeholds in other countries and pulls ahead of Delta there as well, it will help solidify the idea that it’s more transmissible.

To determine whether the variant might undermine immunity generated by vaccines or infection, scientists can draw antibodies from people’s blood and test them against Omicron. But it takes time to grow the variant in labs or to build an engineered version of it that can serve as a model for the virus.

The WHO said Saturday that early evidence indicated the variant was causing reinfections at higher rates than other variants in South Africa, suggesting some ability to get around the immune response.

“Studies are being rapidly conducted in South Africa to look at antibody neutralization of this variant, as well as interactions with T cells, but these studies are going to take several weeks to complete,” said Sharon Peacock, the director of the Covid-19 Genomics UK Consortium. She described the variant as having “several aspects of concern” but with “lots of unknowns.”

With new variants, vaccines can lose a step at blocking infections — particularly if the antibodies they elicit aren’t able to recognize the virus as well — but still largely maintain their ability to guard against severe disease and death because of the broader immune response, including T cells. This has happened already to varying degrees with other variants, to the greatest extent with the Beta variant and even to some extent with Delta. It’s also possible that if there’s a greater degree of immune escape, a higher percentage of breakthrough cases will lead to serious outcomes. That wouldn’t point to complete vaccine failure — but it would point to reduction in vaccine effectiveness.

Joe Phaahla, South Africa’s health minister, said Friday that breakthrough infections were occurring in the country, but the majority of hospital admissions remained among people who were not vaccinated, suggesting that vaccines were still maintaining some level of protection against Omicron. But, he acknowledged, “it’s still early days in terms of this particular variant.”

There is also a question about whether Omicron causes the same disease severity on average as other variants. Studies will look at the rates of people who have Omicron and go on to be hospitalized or die, compared to Delta and other variants.

Omicron was first identified primarily in Botswana and South Africa, but it didn’t necessarily emerge there. Those countries have strong sequencing networks so were in a better place to detect a new variant. Still, many countries, including the United States, have announced restrictions on travel from those countries, as well as their neighbors in southern Africa.

Studies have shown that travel restrictions can slow, but not necessarily hold off, the arrival of variants of a virus like SARS-CoV-2. Case in point: The variant was detected in a handful of European countries even after travel restrictions were announced.

Pathogens generally follow travel patterns as they spread, but there’s also a lot of randomness about whether and when variants will take off in a given place. Some imported infections won’t go anywhere, but others will set off chains of transmissions; the more cases that are introduced, the higher the likelihood that some ignite spread.

Omicron will also underscore the sometimes competing priorities of vaccine campaigns. In wealthy countries that stockpiled vast amounts of  vaccines, it will increase calls for eligible people to get booster shots; if the variant is able to get around the immunity from the primary series to an extent, a booster could help pep up the immune system enough to fend off a highly mutated form of the virus.

An even more transmissible virus will worsen the plight of countries with limited vaccine supplies. Already, advocates were arguing the emergence of Omicron is a demonstration of what happens when the world has such inequitable distribution of vaccines — and transmission is allowed to persist at such high levels in certain parts of the world.

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