/How coronavirus variants called escape mutants threaten to undo all our progress

How coronavirus variants called escape mutants threaten to undo all our progress

For the first time in over a year, people are starting to feel hope that the pandemic has finally turned a corner. Nearly a third of Americans are fully vaccinated, and the Centers for Disease Control and Prevention has relaxed its recommendations on outdoor masks. Europe is on track to be extensively vaccinated by summer’s end. Both Paris and New York have announced they’re reopening for business.

But in reality we’re entering one of the most precarious moments in the pandemic. We’re in a critical race between vaccines and variants of the virus, and despite all the progress we’ve made in recent months, the outcome is far from certain. Fewer than one in 10 people on the planet has had even a single dose of any COVID-19 vaccine, while new and frightening variants are infecting people at a record pace. And that puts all of us — even, in a worst-case scenario, the vaccinated among us — at risk of having to go back to square one.

The situation is so alarming that top public-health experts and virologists I spoke with sound more disheartened about the state of the pandemic now than they did just a few months ago, when it seemed as if vaccines were going to flatten the curve.

“It’s not looking good, just to be totally honest,” the leading virologist Dr. James Hildreth, who serves on the Food and Drug Administration advisory committee that authorizes COVID-19 vaccines, told me. “It seems almost as if the availability of vaccines, and the knowledge that they’re coming, has caused some people to let up their guard a little too soon.”

Scientists who have tracked the spread of variants since the dawn of the pandemic have watched in horror as new, more infectious mutations have taken over. “Until November, most people really didn’t even give variants a second thought,” said the epidemiologist Michael Osterholm, the director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “They were just kind of curiosities, ways to measure how old the virus might be.”

The big question now is, have we seen the worst variations this virus has to offer? More and more, scientists are leaning into the camp of not so sure about that. And that prospect has some of the best virus-watchers worried.

There are 3 ways the variants could win

coronavirus vaccine distribution

The US has vaccinated nearly a third of its population — but that limited immunity may actually create the ideal breeding ground for variants.

Sarah Silbiger/Getty Images


The bad news is, the limited pace of vaccinations means the virus has plenty of opportunities to look for gaps it can exploit in our defenses. As it constantly evolves and adapts to its native habitat — us — the COVID-19 virus is seeking to survive by creating the “fittest” version of itself. Yet all our current vaccines were built to fight the virus first identified in Wuhan, China, nearly a year and a half ago. That version of the virus barely exists anymore, having been outcompeted by newer, fitter variants, including ones that have proved more transmissible, resistant to some vaccines, and able to reinfect people. B.1.1.7, the variant first identified in the UK, is now responsible for most of the COVID-19 cases in the US.

The good news is, the vaccines we have on hand are so powerful they’re standing up well to the mutations. (The notable exception so far is AstraZeneca’s vaccine, which Dr. Anthony Fauci has called “not so good” at warding off the B.1.351 variant first found in South Africa.) What’s more, nearly all the major pharmaceutical companies are scrambling to create new vaccines and booster shots, in the hope that they’ll turn out to be one step ahead of the variants.

There are three important ways the virus could outsmart our vaccines. First, and critically, all the vaccines we have target the coronavirus’ spike proteins, the sharp, crown-like bumps on the surface of the virus that help it invade our cells. If multiple, game-changing mutations occur on the proteins, it could render our current vaccines useless: The antibodies induced by the vaccines would be unable to beat back the new variant. The P.1 variant, first identified in Brazil, has three mutations on the spike protein, and it’s reinfecting people who’ve already had COVID-19.

Second, there’s the possibility of what virologists call “escape mutants” — variations of the virus that are sly enough to slip past any immune defenses we’ve managed to build up. As it happens, the current environment we’ve created, in which we’ve achieved only partial herd immunity, creates the ideal circumstances for escape mutants to arise. Having lots of partially vaccinated people, or communities where viral immunity is low or waning, can put selective pressure on the virus, essentially removing from the competition whichever variants the vaccines work best against.

“Hopefully we won’t have to deal with escape mutants, but it’s not something we can just dismiss offhand, because it could happen,” Hildreth said. “What’s not known is whether, even as we sit here and speak, there’s a person walking around where a combination of mutations has created within that person a variant that is going to spread quickly, and that the vaccines do not work against.”

Full vaccine escape viruses — we’re not necessarily that far away from them.

Other experts share Hildreth’s concern. “Full vaccine escape viruses, we’re not necessarily that far away from them,” said Ravindra Gupta, a microbiology professor at the University of Cambridge who has studied the E484K escape mutation, which is already present in nearly all the most concerning variants. (Scientists have aptly nicknamed it the “eek” variant.)

Third, and perhaps most troubling, even if we don’t wind up being felled by an escape variant, or major changes to the virus’ spike protein, no one knows how long our current vaccines will provide full protection against the virus and its rapidly emerging variants. What scientists are sure about is that vaccine protection won’t last forever, which could make vaccinated people once again vulnerable to the virus in the years ahead — opening the door to another mega wave of infections.

“We will need to — probably this summer into the fall — start planning for that next generation of vaccines,” Dr. Ashish Jha, the dean of the Brown University School of Public Health, said.

The biggest hope

mrna vaccine manufacturing

Scientists are racing to manufacture “messenger RNA” vaccines that train the body to fight the virus on its own.

Abdulhamid Hosbas/Anadolu Agency via Getty Images


Even once we have a large percentage of the population vaccinated, people who are immunocompromised will remain vulnerable to COVID-19 and its long-lasting effects. If we don’t get the pandemic under control fast enough, unvaccinated bodies could become the perfect perpetual breeding ground for variants. That’s another reason it’s wrong to suggest that young people don’t need to be vaccinated: A blanket of protection that covers only half the population won’t do the job.

It’s also possible that vaccinated people who get infected but never develop symptoms could become quiet reservoirs for variants. It’s a scary scenario, especially when you consider that vaccination rates remain shockingly low in states such as Alabama, Mississippi, and Louisiana. Those populations could easily be devastated by new variants.

Even if dreaded escape mutants don’t completely upend our progress, the global outlook for the next couple of years remains bleak. Best-case scenario: The US, Europe, Israel, and perhaps a few other countries achieve high enough levels of vaccination to contain the virus to occasional outbreaks, while the rest of the world continues to face a full-blown pandemic that kills millions and disrupts the global supply chain. It’s worth remembering that most of the world’s vaccines are made not in America but in India, where a crippling wave of COVID-19 infections has bodies piling up so fast they’re being cremated in parking lots.

“That is not the future I want over the next year or two,” Jha said. “And I don’t think that’s the future any of us want.”

Fortunately, scientists agree there is still one big reason for hope. After decades of hard-fought research, new vaccines built on messenger RNA have arrived in impressive force. The beauty of mRNA vaccine technology is that it trains the body to fight the virus on its own, so there’s no need to incubate any viruses in chicken eggs (as we do for annual flu shots), a huge time-saver. New mRNA vaccines can, quite literally, be developed in a weekend. And considering that only two or three variants of the COVID-19 virus seem to be responsible for most of the current hardship, it’s not hard to imagine them being contained by a blockbuster second generation of vaccines. Pfizer and Moderna are already working on their booster shots, and GSK is developing a vaccine that would target several variants at once.

Scientists also hope that given all they’re learning about the new variants, they might one day deliver a single, multi-coronavirus cocktail that would stand up to any and all threats. But even if vaccine developers developed such a dream cocktail — a tall order given that it’s never been done — it’s tricky to make that kind of concoction a success. Trying to train the body to fight numerous versions of the virus at the same time necessarily renders our immune systems less robust at dealing with each single opponent.

In the meantime, we have to move faster to deliver the vaccines that we have to more people. “If people get vaccinated, if we can actually pull that off, then I think we’ll be in much, much better shape than we imagine,” said Dr. Stanley Perlman, a leading virus expert on the FDA’s vaccine advisory committee who’s been studying coronaviruses for nearly four decades.

The biggest threat

India coronavirus

A mass cremation for coronavirus victims in New Delhi on April 22. As the death toll rises in India, experts fear the emergence of new, vaccine-resistant variants.

REUTERS/Danish Siddiqui


Until then, the biggest threat we face is our own complacency. From a global perspective — which is the only one that matters in an epidemiological catastrophe of this magnitude — things are getting worse, not better. More cases of COVID-19 have been reported globally in the past two weeks than during the first six months of the pandemic. More than half of last week’s cases were reported in Brazil and India, where experts fear that even more variants with the potential to evade vaccines are emerging.

At this point, after spending more than a year in various states of lockdown, people are understandably treating vaccinations like a permission slip to get out of detention. Americans are racing toward a summer of untethered fun, with more transatlantic travel and fewer masks. In India, tens of millions of people recently flocked to Kumbh Mela, one of the largest festivals on earth, and many of them subsequently fell ill. And Japan is still pushing to hold the Summer Olympics this year, even though it’s suffered the bulk of its COVID-19 deaths in the past few months.

Right now we’re like an overconfident boxer lowering our guard in the final round. Even if we’ve got the virus on the ropes, we’re giving it a golden opportunity to land a knockout blow. Given how low vaccination rates remain worldwide, the urge to shed our masks and move about freely will only enable the emergence and spread of more variants. Until we’re able to reach something approximating herd immunity, scientists say, we need to realize that vaccinations alone aren’t enough. Basic preventive measures such as masking and distancing remain essential to stopping the spread of COVID-19 and the lethal new variants it’s racing to develop.

“We should be optimistic, with our eyes wide open as to what the possibilities are,” Hildreth told me. “I got vaccinated in December. If I’m out and about, believe me, my mask is on. I realize that I’m protected against the strains the vaccine was developed against. But I don’t know that there’s not a variant out there that might still infect me.”

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