When and how we’ll know if Omicron is worse than Delta
The sudden emergence of Omicron — the dystopian-sounding new coronavirus variant with dozens of mutations that could help it spread more rapidly and partially sidestep our hard-won immune defenses, or not — has ushered in the most disorienting phase of the pandemic since COVID-19 first materialized two winters ago.
“It’s been about 20 months since we’ve been in a fog-of-war situation [with] the pandemic,” evolutionary biologist Carl Bergstrom tweeted Sunday. “But we’re back there with Omicron.”
On the one hand, Omicron is so heavily mutated in such worrisome ways — with more than 50 alterations in total, including up to 32 in its spike protein alone — that one leading infectious-disease researcher described it as “completely insane” upon first encountering a sample, according to a report in the journal Science.
“Just had a look at the list of mutations,” another replied — a list that includes several differences that led to increased transmissibility and breakthrough infections in prior variants. “So nuts.”
On Monday, Moderna Chief Executive Stéphane Bancel went a step further, predicting that Omicron would cause a "material drop" in the effectiveness of the COVID-19 vaccines. "There is no world, I think, where [the effectiveness] is the same level . . . we had with Delta," Bancel told the Financial Times. "All the scientists I've talked to . . . are like 'this is not going to be good.'"
On the other hand, we don’t know much — yet — about how Omicron behaves in the real world.
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The latest on the Omicron variant
“There are three key questions that help scientists understand how consequential any variant might be,” Ashish Jha, dean of the Brown University School of Public Health, wrote Saturday in the New York Times.
“The first question is whether the variant is more transmissible than the current, prevalent Delta strain. Second, does it cause more severe disease? And third, will it render our immune defenses — from vaccines and prior infections — less effective (a phenomenon known as immune escape)?”
Unfortunately, Jha went on to explain, “scientists simply do not have adequate data” to provide any answers “because the variant is so new.”
This gap between what we know about Omicron (very little) and what it has the potential to do (a lot) is deeply distressing — an unwelcome throwback to the pandemic’s earliest, most dizzying days.
The good news is that we’re infinitely more prepared and protected now than we were then, with widespread testing, promising therapies and easy-to-update vaccines. And thanks to the heroic South African researchers who caught Omicron early and immediately alerted the rest of the world, we’re already way ahead of the curve in terms of figuring out what kind of threat it represents — and how to combat it.
Still, as sociologist Zeynep Tufekci tweeted over the weekend, “the earlier the warning, the less we know.”
When exactly will we know more? Here’s a timeline of what to expect in the days ahead:
Any day now
The U.S. will almost certainly find its first Omicron cases.
Omicron has already been detected in South Africa and Botswana, as well as in travelers to Australia, Austria, Belgium, Britain, Canada, Czech Republic, Denmark, Germany, Israel, Italy, the Netherlands, Portugal and Hong Kong.
So far, the U.S. — which lacks the virus surveillance capabilities of many of these countries — hasn’t discovered a single case of its own.
But as Dr. Anthony Fauci, the nation’s top infectious disease expert, put it over the weekend, “when you have a virus that has already gone to multiple countries, inevitably it will be here.”
"The question is,” Fauci continued, “will we be prepared for it?”
The best way for individuals to prepare, explained Francis Collins, director of the National Institutes of Health, is by getting their booster shots.
The booster “basically enlarges the capacity of your immune system to recognize all kinds of different spike proteins it’s never seen,” Collins said on ABC’s “This Week.”
“There’s no reason to panic. But it’s a great reason to go get boosted.”
Fauci agreed. “I don’t think there’s any possibility that this could completely evade any protection by vaccine,” he said. “It may diminish it a bit, but that’s the reason why you boost.”
The first week of December
Some preliminary information on transmission and severity may begin to emerge.
In isolation, Omicron’s mutations look ominous. Our most important antibodies target three sites on SARS-CoV-2’s spike protein; Omicron carries mutations in all three regions, and each of them resemble an earlier mutation known to thwart our immune defenses.
Meanwhile, the part of SARS-CoV-2’s spike that actually makes contact with our cells (the receptor-binding domain) is heavily mutated as well, and a study from last year showed that at least some of these same changes made the virus bind much better — a sign of increased infectiousness.
But mutations don’t operate in isolation; they work together. So the only way to know for sure how Omicron behaves in humans is to study and observe how it behaves in humans. And that takes time.
So far, the signals are mixed.
In South Africa, the initial red flag was a sudden COVID surge in Gauteng, a northern province that encompasses Johannesburg and Pretoria. Subsequent analysis of more than 100 random samples from Gauteng showed that all of them were Omicron.
Over the last two weeks, cases in the province have soared from about 300 a day to 3,220 on Sunday; nationwide, new daily cases have more than tripled in the past week as test positivity has shot up from 2 percent to 10 percent. Early national data suggests that the new variant already makes up the majority of sequenced cases across South Africa.
“I am expecting we will top over 10,000 cases by the end of the week per day,” South African epidemiologist Salim Abdool Karim said during a virtual, government-led news briefing.
It’s possible this could mean that Omicron will spread even more easily than the hypercontagious Delta variant, which is currently causing an average of more than 600,000 new cases per day worldwide. Given its mutations, Jha, for one, says that’s “the more likely scenario.”
But it’s also possible that superspreading events around universities in Gauteng are skewing the picture of Omicron’s relative contagiousness, particularly because Delta prevalence was so low there to begin with and fewer than one in four South Africans are fully vaccinated.
Another possibility is that in terms of infectiousness, Omicron is more like Alpha (with which it shares a key receptor-binding-domain mutation) than the more contagious Delta (which benefits from a different mutation). As the new variant spreads to countries where Delta poses greater competition, and where a higher percentage of the population is vaccinated, we’re likely to find out more.
The same goes for severity. So far, “the proportion of people diagnosed with Covid-19 who have been admitted to hospital over the past two weeks is in line with other waves of infection in South Africa, which were driven by other variants,” the Wall Street Journal reported — and symptoms have been similar as well, according to local doctors.
But because many of the earliest patients appear to be younger (including a worrying number of children under 2 years old); because the absolute number of new daily admissions remains small (around 50); and because it takes time for severe illness to manifest, experts say we won’t know much about the relative virulence of the variant until early next month.
After Dec. 7 or so
Early data on immune evasion will begin to surface.
Initial reports from South Africa suggest that both vaccinated and previously infected people have been testing positive (with relatively mild symptoms) for Omicron — in line with expectations.
But by the second week of December, some solid scientific data on Omicron’s evasiveness should start to appear.
For this, the world has South Africa to thank. “Within an hour of the first alarm, scientists [there] rushed to test coronavirus vaccines against the new variant,” the New York Times reported Sunday. “Now, dozens of teams worldwide — including researchers at Pfizer-BioNTech and Moderna — have joined the chase.”
Perhaps the furthest along is a team led by Penny Moore, a virologist at South Africa’s National Institute for Communicable Diseases, who is preparing to test blood from fully immunized people against a synthetic version of Omicron.
“Creating such a ‘pseudovirus’ — a viral stand-in that contains all of the mutations — takes time,” according to the New York Times, “but results may be available in about 10 days.”
Another team led by Alex Sigal, a virologist at the Africa Health Research Institute, received swabs on Nov. 24 and is already growing live Omicron to “more closely mimic what people are likely to encounter.”
In addition to testing his lab-grown Omicron against the blood of fully vaccinated people, Sigal will also be testing it against blood taken from those who have recovered from infection. Results from Sigal’s lab, which should “provide a fuller picture of the vaccines’ performance,” will probably come out in two to three weeks.
Preparing for the worst, Moderna, Pfizer and Johnson & Johnson are planning to test an artificial version of Omicron against their vaccines. Moderna’s work began last Tuesday, immediately after its scientists learned of Omicron — the fastest the company has ever responded to a variant, Moderna president Stephen Hoge told the Times. They also expect results in two weeks.
“This thing is a Frankenstein mix of all of the greatest hits,” Hoge said. “It just triggered every one of our alarm bells.”
Mid-January 2022 (6-8 weeks from now)
The existing vaccines could be updated to fight Omicron — if necessary.
The good thing about mRNA vaccines (like Pfizer and Moderna) is that they were designed to be easily and rapidly modified in response to threats like Omicron.
The other good thing is that this process is already underway. In addition to bespoke updates, vaccine makers are also testing whether booster shots or larger doses of the original vaccine will bolster the immune system enough to fend off Omicron. But if new formulations are necessary for enhanced protection, then Omicron-specific shots will be ready in a matter of weeks, the companies say.
According to Jerica Pitts, a spokeswoman for Pfizer, the company “can adapt the current vaccine within six weeks.” Pfizer made similar changes for Beta and Delta that ultimately proved unnecessary, and they’ve already crafted their first DNA template for Omicron, the initial step in the development process.
Likewise, Moderna could update its current vaccine in about two months, according to Hoge.
“I don’t think that the result will be the vaccines don’t protect,” Pfizer CEO Albert Bourla told CNBC. “I think the result could be, which we don’t know yet, the vaccines protect less.”
On Monday, President Biden said he was directing the Food and Drug Administration and the Centers for Disease Control and Prevention to use the “fastest process available without cutting any corners” to approve potential Omicron vaccines and speed them to market.
Late February 2022 (three months from now)
A new Omicron vaccine could be ready to ship.
According to Scott Gottlieb, a former commissioner of the Food and Drug Administration who now sits on Pfizer’s board, the FDA can in fact move fast to approve a new version of the vaccine.
Think days or weeks rather than months. “I think the FDA is in a position to move very quickly at this point because they understand the basic platform, the manufacturing has been inspected, they understand the risk benefit of the mRNA platforms generally,” Gottlieb told CBS over the weekend.
Whether that will be necessary remains to be seen. “I would expect that [the early test-tube] studies are going to show that the neutralization against this virus declined substantially,” Gottlieb predicted. “But that doesn't mean that the vaccines won't be effective” — especially when combined with a booster.
“Remember, with the old South African variant [Beta], which also escaped the vaccines, we saw neutralization decline by two thirds in those studies,” he continued. “But when the vaccines actually were put into the population, the mRNA vaccines were almost equally effective against B.1.351 as they were against the Wuhan variant. So, you could see a decline in neutralization” in the lab, but vaccines “will still be effective” in the real world because of how they stimulate other immune defenses.
Either way, Pfizer says it could be ready to “ship initial batches within 100 days”; Moderna says it could have clinical trial results in three months.
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