Scientists see a ‘really, really tough winter’ with Omicron | Science

When South African scientists first alerted the world to the rapid spread of a new SARS-CoV-2 variant, some speculated it might not take off in other countries. After all, an earlier variant named Beta, which dominated in South Africa between November 2020 and May, did not spread much beyond its borders and has since petered out.

Today it’s clear that the world will not be so lucky this time. Although many questions remain, scientists feel increasingly confident that the new arrival, Omicron, is likely to dramatically alter the trajectory of the pandemic—and not for the better.

Omicron has now been found in more than 70 countries and is rapidly gaining ground. As Science went to press, for example, Danish scientists estimated Omicron was just days away from replacing Delta as the most common variant. “What we see is an extraordinary, rapid spread,” says Troels Lillebæk, an infectious disease researcher at the University of Copenhagen. Despite very high vaccination rates, the country of 5 million is now seeing more than 6000 cases a day, roughly twice the number seen during the highest previous peak. (The growth seemed to show signs of slowing down early this week, but that may be in part because the country is reaching the limits of its testing capability.) Neighboring Norway, which has about the same population, is now projecting more than 100,000 cases a day in a matter of weeks, unless people drastically reduce social contacts.

Even if Omicron causes milder disease, as some scientists hope, the astronomical case projections mean the outlook is grim, warns Emma Hodcroft, a virologist at the University of Bern. “A lot of scientists thought Delta was already going to make this a really, really tough winter,” she says. “I’m not sure the message has gotten across to the people who make decisions, how much tougher Omicron is going to make this.”

For Hodcroft and other virologists, immunologists, and epidemiologists, Omicron is another dizzying plunge on the pandemic roller coaster, right before the holidays—a time of frenzied phone calls, late night work, and little sleep. “We have people working the whole weekend again,” says Florian Krammer, a vaccine researcher at the Icahn School of Medicine at Mount Sinai. “It doesn’t matter if something needs to be done at 10 p.m., it’s getting done.”

As with earlier variants, a handful of countries are providing the world with most of the early data. South Africa, where scientists first observed the spread of Omicron, has sequenced a wealth of genomes and produced data about early cases. Denmark, with one of the best genomic surveillance systems in the world, has provided an in-depth view of how Omicron can explode on top of a Delta surge. And scientists in the United Kingdom are conducting a host of studies to nail down how well Omicron transmits in households and elsewhere, and how vaccines are doing against the variant. “We should be pretty grateful” to these countries, Hodcroft says.

As a result, Omicron’s key properties are becoming clearer by the day. It’s beyond doubt that the variant has a substantial growth advantage. What’s less clear is whether that’s mostly because it can evade the human immune response or also because it is inherently more transmissible than its predecessors. That may not matter in the short run, but it does for the long-term outlook. If it’s all about immune evasion, Omicron’s advantage over Delta could wane as immunity to it builds up, and the two could end up cocirculating. If Omicron is also more infectious, it may replace Delta, just as Delta displaced earlier variants.

How good Omicron is at immune escape is also becoming clearer. Preliminary data from South Africa showed its rise coincided with an unexpected surge in reinfections. This past week, laboratory assays by several groups have shown antibodies, whether elicited by vaccines or a previous infection, are significantly less effective at neutralizing Omicron than other variants. And based on the first cases, scientists in the United Kingdom have estimated that protection from symptomatic illness is much lower in people who have received two doses of the AstraZeneca or messenger RNA vaccines. The good news is that boosters appear to bring protection against disease back to about 75%, and probably even higher against hospitalization. “I think it all boils down in the end to protection from severe disease,” Krammer says.

Early data from Discovery, South Africa’s largest health insurer, presented on 14 December, offered some additional reassurance that Omicron’s immune escape isn’t complete. The data showed hospital admissions in the country are growing more slowly than in previous waves. That could mean the protection from severe disease is still robust in vaccinated and recovered people—or the virus is inherently a bit milder than Delta.

But Harvard University epidemiologist William Hanage says the question of severity is still impossible to answer. Recent genomic comparisons suggest Omicron only began to spread in mid-October—earlier work had estimated late September—so the variant hasn’t infected enough people to conclude much of anything, he says. By chance, many of the early cases in South Africa happened to be in younger people, who are less likely to develop severe disease. And even if the variant turns out to be inherently milder, the volume of cases will likely overwhelm health systems. “A colleague put it really well in one of our little depressing Slack channels,” Hanage says: “There’s not much that can spread this fast and be benign to a society that’s already got full hospitals without it.”

Scientists also worry Omicron—which represented a massive leap from known variants in genomic terms—may bring other, unpleasant evolutionary surprises. For instance, roughly one-tenth of Omicron genomes sequenced so far have an additional mutation in the spike protein called 346K that is predicted to make it even better at evading the immune system. “Omicron has most of the greatest hits for antibody escape already, so there aren’t a ton of additions that it could make, but 346K is one of them,” says Stephen Goldstein, a virologist at the University of Utah. “We have to keep an eye on it.”

Given its divergence from earlier variants, Krammer thinks vaccine manufacturers should develop booster shots tailored to Omicron. Obtaining regulatory approval and making such boosters available in large numbers would take months, however—too long to address the crisis many scientists expect. And if the past year is any indicator, they are unlikely to be available to low- and middle-income countries in any meaningful quantities.

For now, most European countries are hoping that providing existing boosters widely, in tandem with added control measures such as a ban on large gatherings, mask mandates, better ventilation, and working from home, will help lower the wave of Omicron infections and prevent hospitals from buckling. Maria Van Kerkhove, an epidemiologist at the World Health Organization, says vaccinating those who have not received any shots at all is still very important—even though it may be too late to get the numbers up substantially. “Get the vaccine into the arms of people who are most at risk,” Van Kerkhove says. “Look to see who you’re missing and focus on these.”