OUT OF SEQUENCE —
As coronavirus variants spread, the US struggles to keep up

Without federal strategy or enough funding, US sequencing superpowers don't work.

MEGAN MOLTENI, WIRED.COM - 2/20/2021

Family business

We tend to use the singular word “coronavirus” when referring to the bug that causes COVID-19. But a more accurate way to think about SARS-CoV-2 is as a population of viruses. And that population is in a state of constant flux—expanding and contracting, mutating, and evolving new lineages as it spreads from person to person. Genetic epidemiologists can track those minute changes, following them like the branches of a family tree to identify clusters of cases all linked to one another. With enough viral genomes, they can also zoom out to compare how fast different branches are growing. If one branch starts to take off, it can indicate that the genetic changes those viruses have acquired provide some kind of competitive advantage. And if a bunch of different branches independently acquire the same mutation, and they all start to take off, well, that’s convergent evolution.

Though the seven variants identified by Cooper, Kamil, Hodcroft, and company appear to have become more common in recent months—accounting for up to 15 percent of the transmission in some places where they have been found—there’s still much the researchers don’t understand about them. Where did they first emerge? Are they spreading faster because the 677 mutation changes the virus’s behavior, as is the case with the other major variants of concern first detected abroad? Or did holiday travel and family gatherings in the US spread it farther and faster than other domestic strains? Even basic questions about the real prevalence of each new variant are hard to answer, because the nation is still so far behind on sequencing.

“What we’ve discovered is just the tip of the iceberg,” says Cooper. Currently the US has sequenced the genomes of just 0.4 percent of all coronavirus cases, according to a WIRED analysis of GISAID data. By comparison, the UK is doing about 10 percent. Denmark, the world leader, has surpassed the 50 percent mark.

“Convergence is actually our friend”

The good news is that all the sequencing being done elsewhere in the world is finding that the virus keeps settling on the same genetic changes in its hunt for an advantage. That suggests it has chanced upon a run of good cards, but there might not be many better ones left in the deck. “In that sense,” says Cooper, “convergence is actually our friend here, because it limits the roster of mutations we have to pay attention to.” That’s not just good for surveillance and testing, but also for vaccine makers trying to future-proof their shots. Any constraints on the number and placement of useful mutations should make it easier to develop an arsenal of boosters that will be effective against whatever variants are yet to emerge.Advertisement


But that doesn’t change the fact that the US is still disastrously unprepared to spot them when they do. As WIRED has previously reported, scaling up a national SARS-CoV-2 monitoring network involves coordinating a patchwork of players—academics like Kamil and Gangavarapu, industry players like Helix, and labs on the front lines, operated by public health departments and hospitals. Connecting sequencing facilities to patient samples and data requires coordination—both in terms of logistics and of agreeing to do things in a standardized way.

All of that takes time and money. Each viral sequence costs between $25 and $400 to generate. So far, the CDC has funded seven universities to the tune of $14.5 million; signed contracts with Illumina, Helix, and medical testing behemoths LabCorp and Quest Diagnostics for $12.5 million; and released a further $15 million to public health labs. But this week, the Biden administration announced it is providing a much needed infusion of cash—almost $200 million—intended to ramp up the nation’s sequencing capacity from 7,000 to 25,000 samples per week. That would put the US on track to capture about 5 percent of new coronavirus cases, provided they continue to decline. It’s a threshold scientists at Illumina estimate the country needs to hit in order to detect a new variant before it grows to more than 1 percent of total cases.
“No consensus”

A spokesperson for the CDC declined to say whether the agency was setting specific targets. “There is currently no consensus in the US or globally on the optimal rate for genomic surveillance,” she wrote in an email to WIRED. In a briefing Wednesday, White House testing czar Carole Johnson described the funding as a “pilot” to tide the CDC over until Congress passes the proposed $1.9 trillion American Rescue Plan. The House version of that bill sets aside $1.75 billion for genomic surveillance.

“It’s really great that we have interest from Congress to invest in this,” says Lane Warmbrod, co-author of a new report from the Johns Hopkins Center for Health Security, outlining recommendations for what an effective SARS-CoV-2 surveillance program should look like. In the short term, she says, labs need money to buy reagents and sequencers, and to hire and train personnel to run them. That includes building up a bioinformatics workforce in public health labs—people who can sort, clean, and interpret the reams of genomic data produced by surveillance sequencing.Advertisement


“The much bigger barrier is the informatics side,” says Warmbrod. In addition to people, that also means computational firepower. She and her colleagues suggest that CPU-strapped public health departments could partner with the Department of Energy, which operates supercomputers around the country, to process increasing loads of genomic data. “We have the capacity and the expertise in this country,” she says. “We just need to incentivize it and put resources where it’ll be most efficient.”
“They’re going to keep coming”

She and her colleagues recommend that funds should go toward coordinating the characterization of variants—which ones should be studied and what experiments scientists should perform. Right now, the old standards of science are still largely being applied. Whoever discovers a variant gets to hold onto it and study it. But when those discoveries could have such a huge effect on human health, Warmbrod argues, the government might want to step in to make sure studies are being done swiftly, safely, and in the public eye. In the longer term, she also believes the US should invest some of those congressional funds in a national pandemic prediction agency to safeguard against emerging threats even after the Covid crisis subsides.

But for now, building up sequencing capacity in whatever way gets it done the fastest should be the highest priority, says Warmbrod. “We know variants are here. We know they’re going to keep coming as long as there’s transmission. These variants could pop up anywhere,” she says. “And right now, in most places in the country, a new variant could be popping up in your backyard, and we’d have no idea because we can’t see it.”

This story originally appeared on wired.com.