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How Will We Know If There’s a Covid Supervariant?

India’s severe outbreak shows why the world needs early warning systems for variants that could evade vaccines.

A lab technician uses a pipette to transfer material.
A lab technician in France works on Covid genome sequencing.

The cognitive dissonance is hard to manage. On the one hand, new Covid cases in the United States are declining as vaccinations rise. A vaccinated summer gleams on the horizon. But internationally, we are at the highest number of new Covid-19 infections ever recorded, the World Health Organization warned last week. And it’s only a matter of time before variants from other outbreaks make their way here.

India is now being ravaged by a near-vertical rise in cases and deaths. Officials and experts fear a new variant that could be both more transmissible and deadlier may be driving it. But it’s almost impossible to tell, for a very simple reason: India is currently sequencing less than 1 percent of its Covid cases.

Despite the measure of security vaccines have already brought many residents of richer nations, they aren’t everywhere yet, and they’re not a final fix. Genomic sequencing and surveillance are now a critical frontier in the global fight: A random sampling of tests can help us detect which variants are circulating or emerging, while more in-depth sequencing needs to be deployed to hot spots. It’s not just about finding variants, Dr. Adam Lauring, associate professor of microbiology and immunology at the University of Michigan Medical School, told me. “It’s also understanding when a variant is concerning.” And a big part of the concern, he said, is “how variants relate to vaccination.” We need to know if a variant develops that can overcome current vaccines so we can control outbreaks and evaluate the need for vaccine boosters.

In July 2020, the National Academies of Science, Engineering, and Medicine published a comprehensive report on the pressing need for genomic surveillance, but the warning largely went unheeded—or, at least, unfunded—for months.

Then, in late December, the world received a wake-up call: Covid-19 was evolving much faster than scientists thought possible—and some of those mutations made it more contagious. “Everyone was surprised,” Dr. Pavitra Roychoudhury, an instructor at the University of Washington’s department of lab medicine and pathology and a research associate in infectious diseases at Fred Hutchinson Cancer Research Center, told me. “Clearly, this has shown that it’s possible for the virus to pick up a lot of mutations that make it more transmissible.”

In the ensuing months, the U.S. government promised billions for genomic sequencing and surveillance, and scientists rapidly increased the number of positive tests scrutinized for variants. But those efforts are still not enough to catch emerging variants, experts say. And we’re already falling behind, because we need not only to be monitoring variants across the country—we also need to be looking in particular at the ones that may make vaccines less effective.

The vaccines we have provide excellent protection against existing variants, but as global cases of Covid reach a record high, particularly in populous countries like India and Brazil, the virus has millions of chances to mutate. The Biden administration announced on Monday that it would deploy a “strike team” to help India conduct viral surveillance, among other goals. That kind of response, however, needs to start happening faster, needs to become a matter of routine, and needs to be integrated into a broader system.

Our existing virus sequencing and surveillance system, like our health care system, is deeply fractured, experts say. Right now, positive Covid cases are usually sequenced by researchers, private businesses, and state and local health departments. These samples are often shared with the U.S. Centers for Disease Control and Prevention and in a global database called GISAID, which is a kind of “data commons” for anyone interested in sequencing, Lauring told me. The CDC’s Advanced Molecular Detection office (which did not return requests for comment) works with state, local, academic, and commercial labs, such as Quest Diagnostics, to pull together a picture of viral changes across the country. But beyond this office, there seems to be no national entity for coordinating efforts to sequence and oversee sequencing. Some of the flaws in this approach can be seen in this map of sequenced cases. Washington state, for instance, is now sequencing about one in 10 positive Covid cases, while Oklahoma has only sequenced about one in 1,000.

“There’s some parts of the country that are fairly densely covered in terms of genomic sequencing, and there are still some kind of dark spots on the map,” Dr. Bronwyn MacInnis, director of pathogen genomic surveillance in the infectious disease and microbiome program at the Broad Institute of MIT and Harvard, told me. “Focal sequencing—being able to be nimble and responsive where there could be epidemiological red flags” could help stem outbreaks before they worsen, she said.

“I think genomic surveillance for respiratory pathogens should become a routine activity for public health entities,” Roychoudhury said. Ideally, these efforts would be centrally coordinated and funded, but the sequencing itself could be done by any public health labs or academic or commercial labs. It’s not just about sequencing the virus; it’s also about sharing what scientists find nationally and internationally, she said.

A national effort would direct resources toward places where sequencing has lagged, especially in hot spots where the virus continues to surge. Creating a unified, coordinated plan to boost surveillance across the country—and the world—will help us find and respond to variants as quickly as possible. And a national strategy for identifying and tracking variants would also help us monitor future virus outbreaks—especially those posing pandemic threats, like the flu. This pandemic, and the vast sums now being allocated to sequencing, could be an opportunity to establish such a system, rather than playing variant whack-a-mole with disjointed sequencing efforts.

Holding all else equal, virologists would expect the virus to pick up a mutation or two every month. But B.1.1.7, the variant first found in the United Kingdom, had at least 17 unique mutations before it was identified, something made possible by the large number of infections.* “I think we were just a bit wrong on that one,” MacInnis told me. “That, I think, comes from not really understanding the enemy, partly because the enemy was still pretty new to us, and not having the global genomic surveillance capacity really in place.”

“That’s when people sat up and started to notice that, Oh, my gosh, we are really lagging behind, we have no idea what’s spreading, because the percentage of positive cases sequenced is so low,” Roychoudhury said. “Since then, I think the spotlight has really shifted from testing to sequencing.”

When the alarm on B.1.1.7 first sounded, only about 51,000 of the 17 million cases confirmed in the U.S. had been sequenced. In January, the U.S. ranked forty-third worldwide for genomic sequencing, said Jeff Zients, the White House’s coronavirus response coordinator. The U.S. has rushed to catch up. On April 16, the Biden administration announced $1.7 billion in funding for genomic sequencing of the virus. In the meantime, the U.S. is now sequencing a little more than 1 percent of its positive Covid tests, compared to about 0.3 percent at the beginning of the year.

But it’s still a far cry from what’s needed. Scientific modelers estimate that randomly sequencing about 5 percent of positive Covid cases should be able to catch existing and emerging variants. Getting closer to 10 percent, as the U.K. does, would ensure that we have an even better handle on the variant picture. And in places where cases explode suddenly, scientists say, sequencing closer to 20 percent of cases is probably a good idea to understand the potential role of variants.

There’s a role for all types of sequencing, in both public and private labs, Lauring told me. But a national effort would help pinpoint the states that have more capacity for sequencing to help the states that don’t. “Not taking away from places that are already doing a bunch, but figuring out a way to get resources or to capture samples from states that might not be sequencing as much,” Lauring said. And the same is true internationally, particularly in countries that have not been able to sequence many of their cases.

Beyond random sampling, it’s important to conduct genomic surveillance on any cases of vaccinated people catching the disease. Testing positive for Covid even when you’ve been fully vaccinated is incredibly rare. More than 87 million people in the U.S. are fully vaccinated, and only 7,157 breakthrough infections have been reported—many of them asymptomatic or mild. The vaccines we have now are astonishingly good at protecting us against the virus. And every infection a vaccine prevents is one less chance for the virus to mutate.

But “are there holes in the coverage that vaccines provide?” Lauring asked. “Are there certain variants that are better at escaping vaccine immunity?” Examining these rare breakthrough cases is the way to find out. If a variant becomes very good at infecting vaccinated people, it could then circulate among unvaccinated people and continue gaining mutations. But if everyone were vaccinated, such a variant would have a lot more trouble taking off. Surveillance can also help detect how a variant is doing in the real world—what sort of transmissibility it has and how well vaccines work against it, outside the lab.

“The virus, like all viruses, will evolve according to the tools that we throw at it.… We’re just starting to reach the level of scale of vaccination in the population where vaccine-mediated evolution and vaccine-mediated variants will likely start to crop up,” MacInnis said. “We just need to get ahead of it. The variants of concern that have been detected and are beginning to be characterized should give us ample warning that this will likely continue to be a problem.”

How quickly such variants develop will depend on how many cases we have. “Every positive case is another opportunity for this virus to replicate and pick up some mutations,” Roychoudhury said. “The more you have, the more worried we should be. Brazil and India are examples of this, because things started to open up in these countries before there was widespread vaccination.… It’s a recipe for disaster.”

But the good news is that platform vaccines can be updated quickly, as long as variants of concern are detected early. Surveillance on how well the vaccines work against variants will help officials decide when and which boosters are needed.

In the meantime, the U.S. should do everything in its power to get vaccines to the rest of the world. “There is a moral imperative,” Lauring said, to vaccinate as many people as possible in order to save lives and keep the virus from evolving. “The more people are vaccinated, the more dead ends there are for the virus,” he said. “If you close off all those pathways to the virus, it’s going to have less chance to evolve into something concerning down the road. That’s a really critical part—not just vaccinations but anything we can do to control SARS-CoV-2.”

“I don’t think that we’ve pushed this [virus] to the limit, and large-scale vaccination will certainly show us what else it can do,” MacInnis said. “It’s an arms race, and I wouldn’t count that we know this enemy well enough to feel like we’ve got it on lock anywhere close to that yet.”

* This article has been updated to clarify what’s known about how Covid-19 mutates.