We’ll know more soon about Omicron. Here’s how to interpret the coming flood of data

At some point in the next few weeks, scientists will start releasing data from lab experiments that can help illuminate just how much of a threat the Omicron variant poses to existing Covid-19 vaccines and our immunity. But there won’t be one clear conclusion reported at one time.

The results will come out in drips — one preprint study posted here, one company press release there. Together, these lab studies, combined with the clinical outcomes of patients infected with the variant, will help experts form a broader understanding of Omicron’s impact — and whether, if it takes off globally, we might need to adapt our vaccines.

Key results will come from studies that involve testing how well antibodies in the blood of people who’ve been vaccinated or recovered from Covid-19 stand up against Omicron. Soon, research teams will report findings such as a drop in neutralizing activity against the variant — it could be, say, a fivefold or 50-fold drop — or some percentage decline in the levels, or titer, of neutralizing antibodies.

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The next step, and a different kind of challenge, is interpreting what those results mean. A bigger drop is worse, obviously. But these studies measure how well just one component of the immune system — neutralizing antibodies — recognizes the variant in question. The body has multiple layers of protection, including other antibodies and immune fighters like T cells. These studies then are like a robber only checking to see how strong of a lock the front door has, without having much clue about the other alarms, defenses, and booby traps that might await.

Indeed, experience with past variants suggests people can lose a decent amount of neutralizing activity and still be well-protected against more serious outcomes. Many experts believe our current levels of immunity should generally protect vaccinated people from severe illness or death even in the face of Omicron, though perhaps they will be more susceptible to infection and mild illness.

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These neutralization studies are incredibly important to help scientists start to understand the scale of immune evasion we could be facing, but what can be extrapolated about what they mean for people in the real world is limited.

“With the neutralization, it gives you more clarity when it’s really, really good, or really, really bad,” said virologist Larissa Thackray of Washington University in St. Louis, who, as part of a federal initiative, has been studying the impact of variants on vaccine responses. A fourfold or fivefold drop is not much to worry about, Thackray said; even a 50-fold drop could be OK if the starting point for the neutralization levels was really high.

But if it’s a, say, 100-fold drop or more, “then you’re really relying on T cell immune responses” and other parts of the immune system that can pick up the new variant, Thackray said.

Even with that kind of decline, a vaccinated person wouldn’t be immunologically “naive” to the virus — meaning there was no protection at all — but it might push regulators and companies to more seriously consider vaccines targeting Omicron specifically.

While antibody titers are seen as a solid correlate for how well-protected someone is against Covid-19 — the higher the level, the better — there’s not a clear threshold for when a drop becomes a serious concern, when even a good percentage of vaccinated people might be vulnerable to developing moderate or worse outcomes.

“We cannot go out and say this is the number above which you are protected, or this is the number below which you are vulnerable,” said Soumya Swaminathan, the World Health Organization’s chief scientist. “It’s a range.”

Neutralization studies involve testing the antibodies against copies of the variant itself grown in lab dishes, or against pseudoviruses, which involve synthesizing the virus’ spike protein — complete with the mutations it’s picked up — and grafting it onto another virus’ backbone. (Scientists have lamented that one consequence of the travel restrictions imposed on South Africa — where some of the first Omicron cases were detected — is that they could delay the sharing of the variant virus with researchers around the world.)

The data won’t come from just one neutralization study. There will be results on antibodies from prior Covid-19 infections, from the different vaccines, and potentially from people who have received boosters. Other research groups will be looking at T cell responses to Omicron, though those are more complicated experiments to conduct.

As they assess the potential impact of Omicron, experts will also be using real-world evidence to monitor vaccine performance. They’ll look, for example, at breakthrough infections caused by the new variant and if they become more common — as well as whether the vast majority of breakthroughs continue to be mild. If more breakthrough infections are leading to hospitalizations or deaths, researchers will try to track which vaccines those people received and when, to understand if one shot is more affected by Omicron than others or is showing worrisome waning. These studies will take time, both because it takes weeks for hospitalizations and deaths to occur after infections, and because there have only been a few hundred cases of Omicron documented globally so far. It’s not clear how widely it will spread.

Lab studies only tell you whether there are “grounds for concern or grounds for some serious concern,” said John Moore, an immunologist at Weill Cornell Medical College. “So you have to keep your eye on the real world. If Omicron takes off in Western countries where there’s a high vaccine rate, what’s going to need to be monitored is whether there are a large number of infected vaccine recipients turning up in hospitals. And that would be grounds for concern.”

Norman Baylor, a former top vaccines official at the Food and Drug Administration, said combining clinical evidence about patient outcomes with the results of the lab studies would inform policy decisions about prioritizing a new Omicron-specific vaccine. “There are a lot of pieces to put together,” he said.

Scientists have been racing to investigate the new variant since researchers in South Africa warned about its potential to escape immunity based on its number and array of mutations.

Even if Omicron is able to evade immunity to concerning levels, regulators and vaccine makers wouldn’t adapt the shots to better match the variant unless it also became dominant globally. That will only occur if Omicron can outcompete the highly transmissible Delta variant. Right now, it appears to be pulling ahead of Delta in South Africa, but that could be a result of something unique in the country’s epidemiological trends or a bias in which cases are being sequenced. Experts will want to see whether Omicron takes off in other countries to get a better sense of any advantage over Delta. The Beta variant, for example, similarly caused worries about immune escape when it emerged last year, but it wasn’t able to compete with other circulating variants, and its prevalence collapsed to the point where it’s no longer considered a global threat.

Experts will also be keeping a close eye on the neutralizing activity against Omicron after a booster dose. Even if antibodies generated by the original vaccine recipe don’t recognize the variant as well because of its mutations, research has suggested booster doses can elevate antibody levels and deepen the immune response in a way that can still counter a highly evolved virus — an instance of quantity overcoming quality. If that holds true, and booster doses enable people to withstand even a variant as mutated as Omicron, it could indicate that vaccines don’t need to be tweaked.

“There’s every reason to believe, as we talk about boosters, when you get a level high enough, that you are going to get at least some degree of cross-protection, particularly against severe disease,” Anthony Fauci, the country’s top infectious disease official, said at a briefing this week.

Helen Branswell contributed reporting. 

Source: STAT