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If the U.S. Already Had a Covid Variant, We Wouldn’t Know

The new U.K. variant making headlines this week was caught with gene sequencing—something the U.S. hasn’t invested in.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, prepares to receive his first dose of the Covid-19 vaccine.

News of specific, potentially more contagious coronavirus variants in the United Kingdom and South Africa have swept global headlines in recent days. The two unrelated variants, health officials say, have spread in the past few weeks, supplanting other variations of the virus and leading officials to believe they are more transmissible. International focus has quickly shifted to containment: Dozens of countries have now issued travel bans for the U.K. The variant has not yet been detected in the United States, the U.S. Centers for Disease Control and Prevention said Tuesday, in a public statement, but only about 51,000 of 17 million cases have been sequenced so far. “Given the small fraction of U.S. infections that have been sequenced, the variant could already be in the United States without having been detected,” the CDC said. Few headlines, though, have focused on the bigger problem: If the U.S. already had its own variants, we wouldn’t know.

Researchers discovered the British and South African variants by sequencing the genomes of virus samples from positive patients. The U.K., the leader in genomic sequencing for Covid-19, examines about 10 percent of all confirmed cases, using the information to guide shelter-in-place recommendations. This month, U.K. researchers have uploaded 2,131 full sequences to an international repository, GISAID. U.S. researchers, on the other hand, have uploaded only 36—despite this country having five times more people and hundreds of thousands of cases. “We’re flying blind. Totally flying blind right now,” Dr. Michael Worobey, head of the ecology and evolutionary biology department at the University of Arizona, told me.

It’s important to track genetic changes to the virus for two main reasons: first, to know whether the variants identified in the U.K. and South Africa are already here, and second, to see what other homegrown variants are emerging. Viruses evolve frequently, making tiny changes every time they replicate. The more chances they have to replicate—each time they infect a new person—the more likely they are to mutate. That means the more cases we have, the more opportunities the virus has to change. Most of these changes are harmless, especially when they happen bit by bit. As the viruses evolve, our immune systems also change to combat them. But when they mutate quickly and substantially, as the U.K. variant has done, they may be able to elude our immune responses, even when we’ve already had an infection or a vaccine. And that’s what has experts worried.

“This is the first variant that got my attention,” Worobey said. “The vast, vast, vast, vast majority of mutations don’t have any important effect. Things are really driven by human behavior. But this is the first one, and the South Africa one is another one, where it’s pretty dramatic.” The variant identified in South Africa spread to account for nearly all of the country’s cases in a matter of weeks. Its three mutations may make it easier for the virus to bind to receptors, officials said, and it seems to increase the patient’s viral load—potentially making them more contagious. In addition, more serious cases than usual have been reported in children and young adults with no preexisting conditions who contract this variant, but it’s not clear whether it’s because young people are more vulnerable to the mutated virus or because many schools have stayed open. This is also a concern with the virus variant in the U.K., with as many as 23 mutations—a surprisingly fast change that experts didn’t expect to see for at least another year—that may aid the virus in spreading significantly faster. “It’s definitely the world record-holder for just a whole bunch of mutations that have never been seen before, all of a sudden, instantaneously, appearing in a new genome,” Worobey said.

It’s still unclear, experts caution, why the variants are spreading so much. While models from Public Health England show a “high confidence” of “substantially increased transmissibility,” that doesn’t mean the virus will actually prove to be more contagious in laboratory experiments. So far, there have been no studies on the virus itself to see if it is actually more contagious. The models predicting its virulence are based on previous transmission patterns, which could be related to other factors like population density or people’s social habits. The U.K. lifted lockdown orders earlier this month, which very likely contributed to the spread of the virus. And it’s possible the U.K. government is now pointing to the rise of the variant in order to implement politically unpopular lockdown measures.

But scientists and officials are taking the new variants seriously—in part because of concern for what these more substantial mutations might mean for the efficacy of vaccines that have only just been released. “There is reason to think that this new variant might actually be able to infect people who have already been affected by earlier variants, because it’s so different,” Worobey said. “And maybe the vaccine might be less protective against this new variant. No one knows the answers to those questions yet; lots of people are working on it rapidly. But it’s a possibility for sure.”

It usually takes a long time for a virus to evolve until a vaccine stops working entirely. More likely, Worobey said, the spread of new variants would simply make a vaccine a little less effective—not negate it completely. Researchers are racing to learn whether the virus has changed enough to reinfect people who already had it, whether the illness is more or less severe, and whether the vaccine still works very well against it. “This is a one-in-a-million event, for sure. Just off the charts,” Worobey said. But one-in-a-million events may become a lot more common when you have a million new cases every four days, as the U.S. now does.

Not only is the U.S. taking fewer measures than other countries to slow transmission (slowing transmission would mean slowing mutation), but it also hasn’t been devoting adequate resources to sequencing. Early in the pandemic, the U.K. government funded the COVID-19 Genomics UK, or COG-UK, consortium to track genomic changes like these. In the U.S., the National Academies of Science, Engineering and Medicine have similarly recommended tracking viral genome sequences (and comparing them with clinical and epidemiological data) in order to gain a much better grasp of how the virus is changing and spreading. So far, those recommendations haven’t been taken up. As Dr. Michal Tal, an instructor at Stanford University’s Institute for Stem Cell Biology and Regenerative Medicine, put it: “You’ll never find what you aren’t actively looking for. We’ve had more transmission and less tracking, so we almost certainly have variants that we aren’t aware of.”

The U.K. response is worth emulating, Tal told me by email. Scientists are already studying antibodies from people who had the virus before or were immunized in the vaccine trials to see how well they neutralize this variant. Moving forward, she said, “this will be an important surveillance strategy, as inevitably additional variants will emerge, as long as there is active transmission and the virus has the opportunity to keep mutating.” Monitoring new variants and testing to make sure the vaccine still works effectively will be key to controlling the virus and ending the pandemic.

Worobey and his team are also developing a relatively simple test to determine whether this variant, and potentially others like it, can be detected in wastewater. They’re running into holiday delays for receiving the materials they need, but they hope to have a test in the next few weeks.

In the meantime, leaders can take steps to keep these variants from spreading and to keep others from emerging. In addition to establishing better genomic tracing and surveillance, this news may provide a new urgency for sheltering in place and rigorous social distancing, continuing to provide health workers with protective gear, ramping up testing—especially tests that can detect variants like these—and rolling the vaccines out quickly, while they’re still highly effective. Especially with the arrival of vaccines, Tal said, “this is like that moment in a battle after a ceasefire is being negotiated, where any deaths that happen now have the additional sting that they really could have been avoided.”

“There’s still a massive disconnect between the seriousness of the situation that we’re in and the reaction and the measures,” Worobey said. “We’ve got a long way to go before vaccines rescue us from that.” The good news, though, is that we already have an extremely effective vaccine. The faster it is deployed, the less time the virus has to evolve. “You don’t want to rule out the possibility that that could be used as a tool to extinguish this outbreak. That should not be off the table yet. And everything we do to allow increased transmission,” he said, “puts us in danger of squandering that opportunity, not just for the U.S. but for the world.”

Nothing about these mutations has changed how the virus is spread or the basic measures needed to slow it. It doesn’t matter what the variant is: If we cut down on the ways it can jump from person to person, the virus will die out. “The bottom line is that we need to suppress transmission of all SARS-CoV-2 viruses as quickly as we can,” said WHO Director-General Tedros Adhanom Ghebreyesus at a recent briefing on the variants. “The more we allow it to spread, the more opportunity it has to change.”